FN Thomson Reuters Web of Science™
VR 1.0
PT J
AU Yaniv, Y
Lakatta, EG
Maltsev, VA
AF Yaniv, Yael
Lakatta, Edward G.
Maltsev, Victor A.
TI From two competing oscillators to one coupled-clock pacemaker cell
system
SO FRONTIERS IN PHYSIOLOGY
LA English
DT Article
DE arrhythmias; coupled-clock pacemaker system; heart rate variability;
mathematical modeling; sinoatrial node
ID SINOATRIAL NODE CELLS; HEART-RATE-VARIABILITY; NONSELECTIVE CATION
CHANNEL; PROTEIN-KINASE-II; L-TYPE CA2+; CARDIAC PACEMAKING; CALCIUM
CLOCK; FUNNY CURRENT; SINUS NODE; AUTONOMIC MODULATION
AB At the beginning of this century, debates regarding "what are the main control mechanisms that ignite the action potential (AP) in heart pacemaker cells" dominated the electrophysiology field. The original theory which prevailed for over 50 years had advocated that the ensemble of surface membrane ion channels (i.e., "M-clock") is sufficient to ignite rhythmic APs. However, more recent experimental evidence in a variety of mammals has shown that the sarcoplasmic reticulum (SR) acts as a "Ca2+-clock" rhythmically discharges diastolic local Ca2+ releases (LCRs) beneath the cell surface membrane. LCRs activate an inward current (likely that of the Na/+Ca2+ exchanger) that prompts the surface membrane "M-clock" to ignite an AP Theoretical and experimental evidence has mounted to indicate that this clock "crosstalk" operates on a beat-to-beat basis and determines both the AP firing rate and rhythm. Our review is focused on the evolution of experimental definition and numerical modeling of the coupled-clock concept, on how mechanisms intrinsic to pacemaker cell determine both the heart rate and rhythm, and on future directions to develop further the coupled-clock pacemaker cell concept.
C1 [Yaniv, Yael] Technion IIT, Biomed Engn Fac, IL-3200003 Haifa, Israel.
[Lakatta, Edward G.; Maltsev, Victor A.] NIA, Cardiovasc Sci Lab, Biomed Res Ctr, Intramural Res Program,NIH, Baltimore, MD 21224 USA.
RP Yaniv, Y (reprint author), Technion IIT, Biomed Engn Fac, IL-3200003 Haifa, Israel.
EM yaely@bm.technion.ac.il; lakattae@grc.nia.nih.gov
FU Intramural Research Program of the NIH, National Institute on Aging;
Technion V.P.R Fund-Mallat Family Research Fund; NSFC-ISF joint research
program [398/14]
FX This research was partially supported by the Intramural Research Program
of the NIH, National Institute on Aging, by Technion V.P.R Fund-Mallat
Family Research Fund (YY) and by NSFC-ISF joint research program, No.
398/14 (YY).
NR 62
TC 11
Z9 11
U1 4
U2 27
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015,
SWITZERLAND
SN 1664-042X
J9 FRONT PHYSIOL
JI Front. Physiol.
PD FEB 13
PY 2015
VL 6
AR UNSP 28
DI 10.3389/fphys.2015.00028
PG 8
WC Physiology
SC Physiology
GA CB0DW
UT WOS:000349296600001
PM 25741284
ER
PT J
AU Wakabayashi, KT
Kiyatkin, EA
AF Wakabayashi, Ken T.
Kiyatkin, Eugene A.
TI Central and peripheral contributions to dynamic changes in nucleus
accumbens glucose induced by intravenous cocaine
SO FRONTIERS IN NEUROSCIENCE
LA English
DT Article
DE high-speed amperometry; enzyme-based glucose sensors; nucleus accumbens;
metabolism; cerebral blood flow; neural activity
ID FREELY MOVING RATS; NATURAL AROUSING STIMULI; CENTRAL-NERVOUS-SYSTEM;
CEREBRAL-BLOOD-FLOW; EXTRACELLULAR GLUCOSE; BRAIN TEMPERATURE;
NEURONAL-ACTIVITY; CARDIOVASCULAR-RESPONSES; CONSCIOUS RATS; RAPID
CHANGES
AB The pattern of neural, physiological and behavioral effects induced by cocaine is consistent with metabolic neural activation, yet direct attempts to evaluate central metabolic effects of this drug have produced controversial results. Here, we used enzyme-based glucose sensors coupled with high-speed amperometry in freely moving rats to examine how intravenous cocaine at a behaviorally active dose affects extracellular glucose levels in the nucleus accumbens (NAc), a critical structure within the motivation-reinforcement circuit. In drug-naive rats, cocaine induced a bimodal increase in glucose, with the first, ultra-fast phasic rise appearing during the injection (latency 6-8s; similar to 50 mu M or similar to 5% of baseline) followed by a larger, more prolonged tonic elevation (similar to 100 mu M or 10% of baseline, peak similar to 15 min). While the rapid, phasic component of the glucose response remained stable following subsequent cocaine injections, the tonic component progressively decreased. Cocaine-methiodide, cocaine's peripherally acting analog, induced an equally rapid and strong initial glucose rise, indicating cocaine's action on peripheral neural substrates as its cause. However, this analog did not induce increases in either locomotion or tonic glucose, suggesting direct central mediation of these cocaine effects. Under systemic pharmacological blockade of dopamine transmission, both phasic and tonic components of the cocaine-induced glucose response were only slightly reduced, suggesting a significant role of non-dopamine mechanisms in cocaine-induced accumbal glucose influx. Hence, intravenous cocaine induces rapid, strong inflow of glucose into NAc extracellular space by involving both peripheral and central, non-dopamine drug actions, thus preventing a possible deficit resulting from enhanced glucose use by brain cells.
C1 [Wakabayashi, Ken T.; Kiyatkin, Eugene A.] NIDA, Behav Neurosci Branch, Intramural Res Program, NIH,DHHS, Baltimore, MD 21224 USA.
RP Kiyatkin, EA (reprint author), NIDA, Behav Neurosci Branch, Intramural Res Program, NIH,DHHS, 333 Cassell Dr, Baltimore, MD 21224 USA.
EM ekiyatki@intra.nida.nih.gov
FU National Institute on Drug Abuse, Intramural Research Program
FX This work was supported by the National Institute on Drug Abuse,
Intramural Research Program.
NR 86
TC 6
Z9 6
U1 1
U2 5
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015,
SWITZERLAND
SN 1662-453X
J9 FRONT NEUROSCI-SWITZ
JI Front. Neurosci.
PD FEB 12
PY 2015
VL 9
AR 42
DI 10.3389/fnins.2015.00042
PG 15
WC Neurosciences
SC Neurosciences & Neurology
GA CG0LB
UT WOS:000352957000002
PM 25729349
ER
PT J
AU Smith, SD
Redman, M
Dunleavy, K
AF Smith, Stephen D.
Redman, Mary
Dunleavy, Kieron
TI FDG PET-CT in follicular lymphoma: a case-based evidence review
SO BLOOD
LA English
DT Review
ID POSITRON-EMISSION-TOMOGRAPHY; NON-HODGKINS-LYMPHOMA; FONDAZIONE ITALIANA
LINFOMI; STANDARDIZED UPTAKE VALUES; MINIMAL RESIDUAL DISEASE; B-CELL
LYMPHOMA; FOLL05 TRIAL; STANFORD-UNIVERSITY; RESPONSE ASSESSMENT;
INITIAL TREATMENT
AB A 52-year-old woman develops right neck lymphadenopathy in the absence of systemic symptoms. Excisional biopsy specimen shows grade 1-2 follicular lymphoma (FL). Physical examination reveals a cluster of 1- to 2-cm right cervical nodes but no other abnormalities. Lactate dehydrogenase is 400 U/L (normal: 140-210 U/L), beta-2 microglobulin is 4.1 mu g/mL (normal: 0-2.5 mu g/mL), and a complete blood count with differential is normal.
18-Fluorodeoxyglucose (FDG) positron emission tomography (PET) with computed tomography (CT) is performed, showing FDG-avid lymphadenopathy above and below the diaphragm, ranging in size from 1.2 to 6 cm. Three FDG-avid lymph nodes measure more than 3 cm. A single 6-cm pelvic node has a maximum standardized uptake value (SUVmax) of 22, and other SUVs range from 6 to 8. An absence of FDG marrow uptake is noted.
How should these PET-CT findings be integrated into further evaluation, prognostication, and treatment recommendations for this patient with FL? Should repeat PET-CT be performed on completion of therapy?
C1 [Smith, Stephen D.] Univ Washington, Sch Med, Dept Med, Div Med Oncol,Seattle Canc Care Alliance, Seattle, WA 98195 USA.
[Redman, Mary] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA.
[Dunleavy, Kieron] NCI, Lymphoid Malignancies Branch, Bethesda, MD 20892 USA.
RP Smith, SD (reprint author), Seattle Canc Care Alliance, Box G3-200, Seattle, WA 98109 USA.
EM ssmith50@u.washington.edu
NR 51
TC 4
Z9 4
U1 1
U2 4
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 FEB 12
PY 2015
VL 125
IS 7
BP 1078
EP 1082
DI 10.1182/blood-2014-11-537522
PG 5
WC Hematology
SC Hematology
GA CD1FB
UT WOS:000350818800009
PM 25527711
ER
PT J
AU Kim, YC
Zhang, AH
Su, Y
Rieder, SA
Rossi, RJ
Ettinger, RA
Pratt, KP
Shevach, EM
Scott, DW
AF Kim, Yong Chan
Zhang, Ai-Hong
Su, Yan
Rieder, Sadiye Amcaoglu
Rossi, Robert J.
Ettinger, Ruth A.
Pratt, Kathleen P.
Shevach, Ethan M.
Scott, David W.
TI Engineered antigen-specific human regulatory T cells: immunosuppression
of FVIII-specific T- and B-cell responses
SO BLOOD
LA English
DT Article
ID LATENT TGF-BETA; FACTOR-VIII; HEMOPHILIA-A; SUPPRESSOR FUNCTION;
IN-VITRO; IMMUNE-RESPONSES; GENE-EXPRESSION; RECEPTOR; FOXP3(+);
ACTIVATION
AB Expansion of human regulatory T cells (Tregs) for clinical applications offers great promise for the treatment of undesirable immune responses in autoimmunity, transplantation, allergy, and antidrug antibody responses, including inhibitor responses in hemophilia A patients. However, polyclonal Tregs are nonspecific and therefore could potentially cause global immunosuppression. To avoid this undesirable outcome, the generation of antigen-specific Tregs would be advantageous. Herein, we report the production and properties of engineered antigen-specific Tregs, created by transduction of a recombinant T-cell receptor obtained from a hemophilia A subject's T-cell clone, into expanded human FoxP3(+) Tregs. Such engineered factor VIII (FVIII)-specific Tregs efficiently suppressed the proliferation and cytokine production of FVIII-specific T-effector cells. Moreover, studies with an HLA-transgenic, FVIII-deficient mouse model demonstrated that antibody production from FVIII-primed spleen cells in vitro were profoundly inhibited in the presence of these FVIII-specific Tregs, suggesting potential utility to treat anti-FVIII inhibitory antibody formation in hemophilia A patients.
C1 [Kim, Yong Chan; Zhang, Ai-Hong; Su, Yan; Rossi, Robert J.; Pratt, Kathleen P.; Scott, David W.] Uniformed Serv Univ Hlth Sci, Dept Med, Bethesda, MD 20814 USA.
[Rieder, Sadiye Amcaoglu; Shevach, Ethan M.] NIAID, Immunol Lab, NIH, Rockville, MD USA.
[Ettinger, Ruth A.] Puget Sound Blood Ctr, Res Inst, Seattle, WA 98104 USA.
RP Scott, DW (reprint author), Uniformed Serv Univ Hlth Sci, Dept Med MED, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA.
EM david.scott@usuhs.edu
FU National Institutes of Health National Heart, Lung, and Blood Institue
[RO1-HL061883-15]; Bayer; CSL Behring; National Institute of Allergy and
Infectious Diseases
FX This work was supported by National Institutes of Health National Heart,
Lung, and Blood Institue grant RO1-HL061883-15 (to D.W.S.), funding from
Bayer and CSL Behring (to K.P.P.), and intramural support from the
National Institute of Allergy and Infectious Diseases (to E.M.S.).
NR 51
TC 21
Z9 22
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 FEB 12
PY 2015
VL 125
IS 7
BP 1107
EP 1115
DI 10.1182/blood-2014-04-566786
PG 9
WC Hematology
SC Hematology
GA CD1FB
UT WOS:000350818800013
PM 25498909
ER
PT J
AU Iqbal, J
Shen, YL
Huang, X
Liu, YY
Wake, L
Liu, CL
Deffenbacher, K
Lachel, CM
Wang, C
Rohr, J
Guo, SP
Smith, LM
Wright, G
Bhagavathi, S
Dybkaer, K
Fu, K
Greiner, TC
Vose, JM
Jaffe, E
Rimsza, L
Rosenwald, A
Ott, G
Delabie, J
Campo, E
Braziel, RM
Cook, JR
Tubbs, RR
Armitage, JO
Weisenburger, DD
Staudt, LM
Gascoyne, RD
McKeithan, TW
Chan, WC
AF Iqbal, Javeed
Shen, Yulei
Huang, Xin
Liu, Yanyan
Wake, Laura
Liu, Cuiling
Deffenbacher, Karen
Lachel, Cynthia M.
Wang, Chao
Rohr, Joseph
Guo, Shuangping
Smith, Lynette M.
Wright, George
Bhagavathi, Sharathkumar
Dybkaer, Karen
Fu, Kai
Greiner, Timothy C.
Vose, Julie M.
Jaffe, Elaine
Rimsza, Lisa
Rosenwald, Andreas
Ott, German
Delabie, Jan
Campo, Elias
Braziel, Rita M.
Cook, James R.
Tubbs, Raymond R.
Armitage, James O.
Weisenburger, Dennis D.
Staudt, Louis M.
Gascoyne, Randy D.
McKeithan, Timothy W.
Chan, Wing C.
TI Global microRNA expression profiling uncovers molecular markers for
classification and prognosis in aggressive B-cell lymphoma
SO BLOOD
LA English
DT Article
ID GERMINAL CENTER; BURKITTS-LYMPHOMA; TUMOR-SUPPRESSOR; GASTRIC-CANCER;
R-CHOP; SURVIVAL; PATHWAY; DIAGNOSIS; PROTEIN; GROWTH
AB We studied the global microRNA (miRNA) expression in diffuse large B-cell lymphoma (DLBCL; n = 79), Burkitt lymphoma (BL; n = 36), primary mediastinal B-cell lymphoma (PMBL; n = 12), B-cell lines (n = 11), and normal subsets of naive B cells, centroblasts (CBs), and peripheral blood B cells along with their corresponding gene expression profiles (GEPs). The normal B-cell subsets have well-defined miRNA signatures. The CB miRNA signature was significantly associated with germinal center B-cell (GCB)-DLBCL compared with activated B-cell (ABC)-DLBCL (P = .002). We identified a 27-miRNA signature that included v-myc avian myelomatosis viral oncogene homolog(MYC) targets and enabled the differentiation of BL from DLBCL, a distinction comparable with the "gold standard" GEP-defined diagnosis. Distinct miRNA signatures were identified for DLBCL subgroups, including GCB-DLBCL, activated B-cell (ABC)-DLBCL, and PMBL. Interestingly, most of the unclassifiable-DLBCL by GEP showed a strong similarity to the ABC-DLBCL by miRNA expression profiling. Consistent results for BL and DLBCL subgroup classification were observed in formalin-fixed, paraffin-embedded tissue, making such tests practical for clinical use. We also identified predictive miRNA biomarker signatures in DLBCL, including high expression of miR-155, which is significantly associated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) treatment failure. This finding was further supported by the observation that high expression of miR-155 sensitizes cells to v-akt murine thymoma viral oncogene homolog-1 inhibitors in vitro, suggesting a novel treatment option for resistant DLBCL.
C1 [Iqbal, Javeed; Shen, Yulei; Huang, Xin; Liu, Yanyan; Wake, Laura; Liu, Cuiling; Deffenbacher, Karen; Lachel, Cynthia M.; Wang, Chao; Rohr, Joseph; Guo, Shuangping; Bhagavathi, Sharathkumar; Fu, Kai; Greiner, Timothy C.; McKeithan, Timothy W.; Chan, Wing C.] Univ Nebraska Med Ctr, Dept Pathol & Microbiol, Omaha, NE 68105 USA.
[Smith, Lynette M.] Univ Nebraska Med Ctr, Coll Publ Hlth, Omaha, NE 68105 USA.
[Wright, George; Staudt, Louis M.] NCI, Metab Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Dybkaer, Karen] Aalborg Univ Hosp, Dept Hematol, Aalborg, Denmark.
[Vose, Julie M.; Armitage, James O.] Univ Nebraska Med Ctr, Dept Hematol Oncol, Omaha, NE 68105 USA.
[Jaffe, Elaine] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Rimsza, Lisa] Univ Arizona, Dept Pathol, Tucson, AZ USA.
[Rosenwald, Andreas] Univ Wurzburg, Dept Pathol, Wurzburg, Germany.
[Ott, German] Robert Bosch Krankenhaus, Dr Margareta Fischer Bosch Inst Clin Pharmacol, Dept Clin Pathol, Stuttgart, Germany.
[Delabie, Jan] Univ Oslo, Norwegian Radium Hosp, Dept Pathol, Oslo, Norway.
[Campo, Elias] Univ Barcelona, Hosp Clin, Barcelona, Spain.
[Braziel, Rita M.] Oregon Hlth & Sci Univ, Clin Pathol, Portland, OR 97201 USA.
[Cook, James R.; Tubbs, Raymond R.] Cleveland Clin, Robert J Tomsich Pathol & Lab Med Inst, Cleveland, OH 44106 USA.
[Weisenburger, Dennis D.; McKeithan, Timothy W.; Chan, Wing C.] City Hope Natl Med Ctr, Dept Pathol, Duarte, CA 91010 USA.
[Gascoyne, Randy D.] British Columbia Canc Agcy, Ctr Lymphoid Canc, Vancouver, BC V5Z 4E6, Canada.
RP Iqbal, J (reprint author), Univ Nebraska Med Ctr, Dept Pathol & Microbiol, LTC 11714,Zip 7760, Omaha, NE 68105 USA.
EM jiqbal@unmc.edu; jochan@coh.org
RI Campo, elias/O-7192-2016;
OI Campo, elias/0000-0001-9850-9793; McKeithan, Timothy/0000-0003-2242-3074
FU National Institutes of Health National Cancer Institute
[1U01CA157581-01]; Lymphoma Research Foundation; Leukemia & Lymphoma
Society; University of Nebraska Medical Center (UNMC)-Clinical and
Translational Research mentored Scholars program pilot grant
FX This work was supported by a grant from the National Institutes of
Health National Cancer Institute (1U01CA157581-01 [W.C.C.]) and is part
of the Lymphoma/Leukemia Molecular profiling project (LLMPP). J.I. has
received support from the Lymphoma Research Foundation, the Leukemia &
Lymphoma Society, and the University of Nebraska Medical Center
(UNMC)-Clinical and Translational Research mentored Scholars program
pilot grant.
NR 52
TC 21
Z9 22
U1 2
U2 10
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 FEB 12
PY 2015
VL 125
IS 7
BP 1137
EP 1145
DI 10.1182/blood-2014-04-566778
PG 9
WC Hematology
SC Hematology
GA CD1FB
UT WOS:000350818800016
PM 25498913
ER
PT J
AU He, JT
Schepmoes, AA
Shi, TJ
Wu, CC
Fillmore, TL
Gao, YQ
Smith, RD
Qian, WJ
Rodland, KD
Liu, T
Camp, DG
Rastogi, A
Tan, SH
Yan, WS
Mohamed, AA
Huang, W
Banerjee, S
Kagan, J
Srivastava, S
McLeod, DG
Srivastava, S
Petrovics, G
Dobi, A
Srinivasan, A
AF He, Jintang
Schepmoes, Athena A.
Shi, Tujin
Wu, Chaochao
Fillmore, Thomas L.
Gao, Yuqian
Smith, Richard D.
Qian, Wei-Jun
Rodland, Karin D.
Liu, Tao
Camp, David G., II
Rastogi, Anshu
Tan, Shyh-Han
Yan, Wusheng
Mohamed, Ahmed A.
Huang, Wei
Banerjee, Sreedatta
Kagan, Jacob
Srivastava, Sudhir
McLeod, David G.
Srivastava, Shiv
Petrovics, Gyorgy
Dobi, Albert
Srinivasan, Alagarsamy
TI Analytical platform evaluation for quantification of ERG in prostate
cancer using protein and mRNA detection methods
SO JOURNAL OF TRANSLATIONAL MEDICINE
LA English
DT Article
DE ERG; Quantification; Biomarker; PRISM-SRM; MRM; Mass spectrometry;
ELISA; Prostate cancer; Diagnosis
ID TARGETED QUANTIFICATION; QUANTITATIVE PROTEOMICS; ONCOPROTEIN
EXPRESSION; GENE-EXPRESSION; ANTIBODY-FREE; FUSION; STRATIFICATION;
PROGRESSION; FREQUENCY; ONCOGENE
AB Background: The established methods for detecting prostate cancer (CaP) are based on tests using PSA (blood), PCA3 (urine), and AMACR (tissue) as biomarkers in patient samples. The demonstration of ERG oncoprotein overexpression due to gene fusion in CaP has thus provided ERG as an additional biomarker. Based on this, we hypothesized that ERG protein quantification methods can be of use in the diagnosis of prostate cancer.
Methods: An antibody-free assay for ERG3 protein detection was developed based on PRISM (high-pressure high-resolution separations with intelligent selection and multiplexing)-SRM (selected reaction monitoring) mass spectrometry. We utilized TMPRSS2-ERG positive VCaP and TMPRSS2-ERG negative LNCaP cells to simulate three different sample types (cells, tissue, and post-DRE urine sediment). Enzyme-linked immunosorbent assay (ELISA), western blot, NanoString, and qRT-PCR were also used in the analysis of these samples.
Results: Recombinant ERG3 protein spiked into LNCaP cell lysates could be detected at levels as low as 20 pg by PRISM-SRM analysis. The sensitivity of the PRISM-SRM assay was approximately 10,000 VCaP cells in a mixed cell population model of VCaP and LNCaP cells. Interestingly, ERG protein could be detected in as few as 600 VCaP cells spiked into female urine. The sensitivity of the in-house ELISA was similar to the PRISM-SRM assay, with detection of 30 pg of purified recombinant ERG3 protein and 10,000 VCaP cells. On the other hand, qRT-PCR exhibited a higher sensitivity, as TMPRSS2-ERG transcripts were detected in as few as 100 VCaP cells, in comparison to NanoString methodologies which detected ERG from 10,000 cells.
Conclusions: Based on this data, we propose that the detection of both ERG transcriptional products with RNA-based assays, as well as protein products of ERG using PRISM-SRM assays, may be of clinical value in developing diagnostic and prognostic assays for prostate cancer given their sensitivity, specificity, and reproducibility.
C1 [He, Jintang; Schepmoes, Athena A.; Shi, Tujin; Wu, Chaochao; Gao, Yuqian; Smith, Richard D.; Qian, Wei-Jun; Rodland, Karin D.; Liu, Tao; Camp, David G., II] Pacific NW Natl Lab, Div Biol Sci, Richland, WA 99352 USA.
[Fillmore, Thomas L.] Pacific NW Natl Lab, Environm Mol Sci Lab, Richland, WA 99352 USA.
[Rastogi, Anshu; Tan, Shyh-Han; Yan, Wusheng; Mohamed, Ahmed A.; Huang, Wei; Banerjee, Sreedatta; McLeod, David G.; Srivastava, Shiv; Petrovics, Gyorgy; Dobi, Albert; Srinivasan, Alagarsamy] Uniformed Serv Univ Hlth Sci, Dept Surg, Ctr Prostate Dis Res, Bethesda, MD 20814 USA.
[Kagan, Jacob; Srivastava, Sudhir] NCI, Canc Biomarkers Res Grp, Canc Prevent Div, Bethesda, MD 20892 USA.
[McLeod, David G.] Walter Reed Natl Mil Med Ctr, Urol Serv, Bethesda, MD USA.
RP Srinivasan, A (reprint author), Uniformed Serv Univ Hlth Sci, Dept Surg, Ctr Prostate Dis Res, Bethesda, MD 20814 USA.
EM asrinivasan@cpdr.org
RI Smith, Richard/J-3664-2012;
OI Smith, Richard/0000-0002-2381-2349; Tan, Shyh-Han/0000-0001-8250-7005
FU National Cancer Institute (NCI) Early Detection Research Network (EDRN)
Interagency Agreement [ACN12003-001-00000]; National Institutes of
Health [P41GM103493]; DoD/CDMRP/PCRP [PC073614]; NCI/EDRN
[ACN12011-001-0]; Department of Energy and located at Pacific Northwest
National Laboratory; Department of Energy [DE-AC05-76RL0 1830]; Center
for Prostate Disease Research; Basic Science Research Program;
Department of Surgery, at Uniformed Services University of the Health
Sciences
FX Portions of this work were supported by the National Cancer Institute
(NCI) Early Detection Research Network (EDRN) Interagency Agreement
ACN12003-001-00000 (to K.D.R. and D.G.C.) and National Institutes of
Health grant P41GM103493 (to R.D.S.), as well as the DoD/CDMRP/PCRP
grant PC073614 (to S.S.) and the NCI/EDRN ACN12011-001-0 (to S.S.). The
experimental work described herein was performed in the Environmental
Molecular Sciences Laboratory, a national scientific user facility
sponsored by the Department of Energy and located at Pacific Northwest
National Laboratory, which is operated by Battelle Memorial Institute
for the Department of Energy under Contract DE-AC05-76RL0 1830, as well
as The Center for Prostate Disease Research, under the Basic Science
Research Program under the Department of Surgery, at the Uniformed
Services University of the Health Sciences.
NR 38
TC 7
Z9 8
U1 2
U2 10
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1479-5876
J9 J TRANSL MED
JI J. Transl. Med.
PD FEB 12
PY 2015
VL 13
AR 54
DI 10.1186/s12967-015-0418-z
PG 14
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA CC6VL
UT WOS:000350507000003
PM 25889691
ER
PT J
AU Yi, CJ
Wu, CO
Tee, M
Liu, CY
Volpe, GJ
Prince, MR
Hundley, GW
Gomes, AS
van der Geest, RJ
Heckbert, S
Lima, JA
Bluemke, DA
AF Yi, Colin J.
Wu, Colin O.
Tee, Michael
Liu, Chia-Ying
Volpe, Gustavo J.
Prince, Martin R.
Hundley, Gregory W.
Gomes, Antoinette S.
van der Geest, Rob J.
Heckbert, Susan
Lima, Joao A.
Bluemke, David A.
TI The association between cardiovascular risk and cardiovascular magnetic
resonance measures of fibrosis: the Multi-Ethnic Study of
Atherosclerosis (MESA)
SO JOURNAL OF CARDIOVASCULAR MAGNETIC RESONANCE
LA English
DT Article
DE Myocardium; Cardiovascular magnetic resonance; Risk factors
ID DIFFUSE MYOCARDIAL FIBROSIS; CORONARY-HEART-DISEASE; CARDIAC FIBROSIS;
FABRY DISEASE; PROFESSIONALS; CHOLESTEROL; FRAMINGHAM; STATEMENT;
FAILURE; CALCIUM
AB Background: Risk scores for cardiovascular disease (CVD) are in common use to integrate multiple cardiovascular risk factors in order to identify individuals at greatest risk for disease. The purpose of this study was to determine if individuals at greater cardiovascular risk have T-1 mapping indices by cardiovascular magnetic resonance (CMR) indicative of greater myocardial fibrosis.
Methods: CVD risk scores for 1208 subjects (men, 50.8%) ages 55-94 years old were evaluated in the Multiethnic Study of Atherosclerosis (MESA) at six centers. T-1 times were determined at 1.5Tesla before and after gadolinium administration (0.15 mmol/kg) using a modified Look-Locker pulse sequence. The relationship between CMR measures (native T-1, 12 and 25 minute post-gadolinium T-1, partition coefficient and extracellular volume fraction) and 14 established different cardiovascular risk scores were determined using regression analysis. Bootstrapping analysis with analysis of variance was used to compare different CMR measures. CVD risk scores were significantly different for men and women (p < 0.001).
Results: 25 minute post gadolinium T-1 time showed more statistically significant associations with risk scores (10/14 scores, 71%) compared to other CMR indices (e. g. native T-1 (7/14 scores, 50%) and partition coefficient (7/14, 50%) in men. Risk scores, particularly the new 2013 AHA/ASCVD risk score, did not correlate with any CMR fibrosis index.
Conclusions: Men with greater CVD risk had greater CMR indices of myocardial fibrosis. T-1 times at greater delay time (25 minutes) showed better agreement with commonly used risk score indices compared to ECV and native T-1 time.
C1 [Yi, Colin J.; Tee, Michael; Liu, Chia-Ying; Bluemke, David A.] NIH, Bethesda, MD 20892 USA.
[Volpe, Gustavo J.; Lima, Joao A.; Bluemke, David A.] Johns Hopkins Univ, Dept Med, Baltimore, MD USA.
[Prince, Martin R.] Cornell Univ, Cornell MRI Facil, Ithaca, NY USA.
[Hundley, Gregory W.] Wake Forest Univ, Winston Salem, NC 27109 USA.
[Gomes, Antoinette S.] Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA.
[van der Geest, Rob J.] Leiden Univ, Med Ctr, Dept Radiol, Leiden, Netherlands.
[Heckbert, Susan] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.
[Wu, Colin O.] NHLBI, Off Biostat Res, Bethesda, MD 20892 USA.
RP Bluemke, DA (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA.
EM bluemked@nih.gov
RI van der Geest, Rob/J-8193-2015; Prince, Martin/S-6850-2016;
OI van der Geest, Rob/0000-0002-9084-5597; Bluemke,
David/0000-0002-8323-8086; Prince, Martin/0000-0002-9883-0584
FU National Heart, Lung, and Blood Institute [N01-HC-95159, N01-HC-95166,
N01-HC-95169]; NIH research program
FX This research was supported by contracts N01-HC-95159 through
N01-HC-95166 and N01-HC-95169 from the National Heart, Lung, and Blood
Institute and the intramural NIH research program. Gadolinium contrast
was provided without charge by Bayer Healthcare. We thank the other
investigators, staff, and participants of the MESA and MESA-Lung Studies
for their valuable contributions. A full list of participating MESA
Investigators and institutions can be found at
http://www.mesa-nhlbi.org.
NR 32
TC 4
Z9 4
U1 0
U2 1
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 FEB 12
PY 2015
VL 17
AR 15
DI 10.1186/s12968-015-0121-5
PG 11
WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical
Imaging
SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine &
Medical Imaging
GA CB9IQ
UT WOS:000349945600004
PM 25827220
ER
PT J
AU Subramanian, V
Knight, JS
Parelkar, S
Anguish, L
Coonrod, SA
Kaplan, MJ
Thompson, PR
AF Subramanian, Venkataraman
Knight, Jason S.
Parelkar, Sangram
Anguish, Lynne
Coonrod, Scott A.
Kaplan, Mariana J.
Thompson, Paul R.
TI Design, Synthesis, and Biological Evaluation of Tetrazole Analogs of
CI-Amidine as Protein Arginine Deiminase Inhibitors
SO JOURNAL OF MEDICINAL CHEMISTRY
LA English
DT Article
ID NEUTROPHIL EXTRACELLULAR TRAPS; SYSTEMIC-LUPUS-ERYTHEMATOSUS;
PEPTIDYLARGININE DEIMINASE; RHEUMATOID-ARTHRITIS;
PROTEIN-ARGININE-DEIMINASE-4 PAD4; CITRULLINATED PROTEINS; IN-VITRO;
MURINE MODELS; CL-AMIDINE; PATHOGENESIS
AB Protein arginine deiminases (PADs) catalyze the post-translational hydrolysis of arginine residues to form citrulline. This once obscure modification is now known to play a key role in the etiology of multiple autoimmune diseases (e.g., rheumatoid arthritis, multiple sclerosis, lupus, and ulcerative colitis) and in some forms of cancer. Among the five human PADs (PAD1, -2, -3, -4, and -6), it is unclear which isozyme contributes to disease pathogenesis. Toward the identification of potent, selective, and bioavailable PAD inhibitors that can be used to elucidate the specific roles of each isozyme, we describe tetrazole analogs as suitable backbone amide bond bioisosteres for the parent pan PAD inhibitor Cl-amidine. These tetrazole based analogs are highly potent and show selectivity toward particular isozymes. Importantly, one of the compounds, biphenyl tetrazole tert-butyl Cl-amidine (compound 13), exhibits enhanced cell killing in a PAD4 expressing osteosarcoma bone marrow (U2OS) cell line and can also block the formation of neutrophil extracellular traps. These bioisosteres represent an important step in our efforts to develop stable, bioavailable, and selective inhibitors for the PADs.
C1 [Subramanian, Venkataraman; Parelkar, Sangram; Thompson, Paul R.] Univ Massachusetts, Sch Med, Dept Biochem & Mol Pharmacol, Worcester, MA 01605 USA.
[Knight, Jason S.] Univ Michigan, Sch Med, Div Rheumatol, Ann Arbor, MI 48109 USA.
[Anguish, Lynne; Coonrod, Scott A.] Cornell Univ, Coll Vet Med, Baker Inst Anim Hlth, Dept Mol Biol & Genet, Ithaca, NY 14853 USA.
[Kaplan, Mariana J.] NIAMSD, Bethesda, MD 20892 USA.
RP Thompson, PR (reprint author), Univ Massachusetts, Sch Med, Dept Biochem & Mol Pharmacol, 364 Plantat St, Worcester, MA 01605 USA.
EM Paul.Thompson@umassmed.edu
FU NIH [GM079357, GM110394]; NIAMS
FX The authors are most grateful to Rose L. Szabady and Beth McCormick for
providing the human neutrophils for the cytotoxicity studies. Financial
support for this work was provided by NIH Grants GM079357 (P.R.T.) and
GM110394 (P.R.T. and S.A.C.) and in part by the intramural research
program at NIAMS.
NR 60
TC 11
Z9 11
U1 3
U2 39
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 FEB 12
PY 2015
VL 58
IS 3
BP 1337
EP 1344
DI 10.1021/jm501636x
PG 8
WC Chemistry, Medicinal
SC Pharmacology & Pharmacy
GA CB4BS
UT WOS:000349573800024
PM 25559347
ER
PT J
AU Shungin, D
Winkler, TW
Croteau-Chonka, DC
Ferreira, T
Lockes, AE
Magi, R
Strawbridge, RJ
Pers, TH
Fischer, K
Justice, AE
Workalemahu, T
Wu, JMW
Buchkovich, ML
Heard-Costa, NL
Roman, TS
Drong, AW
Song, C
Gustafsson, S
Day, FR
Esko, T
Fall, T
Kutalik, Z
Luan, JA
Randall, JC
Scherag, A
Vedantam, S
Wood, AR
Chen, J
Fehrmann, R
Karjalainen, J
Kahali, B
Liu, CT
Schmidt, EM
Absher, D
Amin, N
Anderson, D
Beekman, M
Bragg-Gresham, JL
Buyske, S
Demirkan, A
Ehret, GB
Feitosa, MF
Goel, A
Jackson, AU
Johnson, T
Kleber, ME
Kristiansson, K
Mangino, M
Leach, IM
Medina-Gomez, C
Palmer, CD
Pasko, D
Pechlivaniss, S
Peters, MJ
Prokopenko, I
Stancakova, A
Sung, YJ
Tanakam, T
Teumer, A
Van Vliet-Ostaptchouk, JV
Yengo, L
Zhang, WH
Albrecht, E
Arnlov, J
Arscott, GM
Bandinelli, S
Barrett, A
Bellis, C
Bennett, AJ
Berne, C
Bluher, M
Buhringer, S
Bonnet, F
Bottcher, Y
Bruinenberg, M
Carba, DB
Caspersen, IH
Clarke, R
Daw, EW
Deelen, J
Deelman, E
Delgado, G
Doney, ASF
Eklund, N
Erdos, MR
Estrada, K
Eury, E
Friedrichs, N
Garcia, ME
Giedraitis, V
Gigante, B
Go, AS
Golay, A
Grallert, H
Grammer, TB
Grassler, J
Grewal, J
Groves, CJ
Haller, T
Hallmans, G
Hartman, CA
Hassinen, M
Hayward, C
Heikkila, K
Herzig, KH
Helmer, Q
Hillege, HL
Holmen, O
Hunt, SC
Isaacs, A
Ittermann, T
James, AL
Johansson, I
Juliusdottir, T
Kalafati, IP
Kinnunen, L
Koenig, W
Kooner, IK
Kratzer, W
Lamina, C
Leander, K
Lee, NR
Lichtner, P
Lind, L
Lindstrom, J
Lobbens, S
Lorentzon, M
Mach, F
Magnusson, PKE
Mahajan, A
McArdle, WL
Menni, C
Merger, S
Mihailov, E
Milani, L
Mills, R
Moayyeri, A
Monda, KL
Mooijaart, SP
Muhleisen, TW
Mulas, A
Muller, G
Muller-Nurasyid, M
Nagaraja, R
Nalls, MA
Narisu, N
Glorioso, N
Nolte, IM
Olden, M
Rayner, NW
Renstrom, F
Ried, JS
Robertson, NR
Rose, LM
Sanna, S
Scharnagl, H
Scholtens, S
Sennblad, B
Seufferlein, T
Sitlani, CM
Smith, AV
Stirrups, K
Stringhams, HM
Sundstrom, J
Swertz, MA
Swift, AJ
Syvanen, AC
Tayo, BO
Thorand, B
Thorleifsson, G
Tomaschitz, A
Troffa, C
van Oort, FVA
Verweij, N
Vonk, JM
Waite, LL
Wennauer, R
Wilsgaard, T
Wojczynski, MK
Wong, A
Zhang, QY
Zhao, JH
Brennan, EP
Choi, M
Eriksson, P
Folkersen, L
Franco-Cereceda, A
Gharavi, AG
Hedman, AK
Hivert, MF
Huang, JY
Kanoni, S
Karpe, F
Keildson, S
Kiryluk, K
Liang, LM
Lifton, RP
Ma, BS
McKnight, AJ
McPherson, R
Metspalu, A
Min, JL
Moffatt, MF
Montgomery, GW
Murabito, JM
Nicholson, G
Nyholt, DR
Olsson, C
Perry, JRB
Reinmaa, E
Salem, RM
Sandholm, N
Schadt, EE
Scott, R
Stolk, L
Vallejo, EE
Westra, HJ
Zondervan, KT
Amouyel, P
Arveiler, D
Bakker, SJL
Beilby, J
Bergman, RN
Blangero, J
Brown, MJ
Burnier, M
Campbell, H
Chakravarti, A
Chiness, PS
Claudi-Boehmi, S
Collins, FS
Crawford, DC
Danesh, J
de Faire, U
de Geusl, EJC
Dorr, M
Erbel, R
Eriksson, JG
Farrall, M
Ferrannini, E
Ferrieres, J
Forouhi, NG
Forrester, T
Franco, OH
Gansevoort, RT
Gieger, C
Gudnason, V
Haiman, CA
Harris, TB
Hattersley, AT
Heliovaara, M
Hicks, AA
Hingorani, AD
Hoffmann, W
Hofman, A
Homuth, G
Humphries, SE
Hypponen, E
Illig, T
Jarvelin, MR
Johansen, B
Jousilahti, P
Jula, AM
Kaprio, J
Kee, F
Keinanen-Kiukaanniemi, SM
Kooner, JS
Kooperberg, C
Kovacs, P
Kraja, AT
Kumari, M
Kuulasmaa, K
Kuusisto, J
Lakka, TA
Langenberg, C
Le Marchand, L
Lehtimaki, T
Lyssenko, V
Mannisto, S
Marette, A
Matise, TC
McKenzie, CA
McKnight, B
Musk, AW
Mohlenkamp, S
Morris, AD
Nelis, M
Ohlsson, C
Oldehinkel, AJ
Ong, KK
Palmer, LJ
Penninx, BW
Peters, A
Pramstaller, PP
Raitakari, OT
Rankinen, T
Rao, DC
Rice, TK
Ridker, PM
Ritchie, MD
Rudan, I
Salomaa, V
Samani, NJ
Saramies, J
Sarzynski, MA
Schwarz, PEH
Shuldiner, AR
Staessen, JA
Steinthorsdottir, V
Stolk, RP
Strauch, K
Tonjes, A
Tremblay, A
Tremoli, E
Vohl, MC
Volker, U
Vollenweider, P
Wilson, JF
Witteman, JC
Adair, LS
Bochud, M
Boehm, BO
Bornstein, SR
Bouchard, C
Cauchi, S
Caulfield, MJ
Chambers, JC
Chasman, DI
Cooper, RS
Dedoussis, G
Ferrucci, L
Froguel, P
Grabe, HJ
Hamsten, A
Hui, JN
Hveem, K
Jockel, KH
Kivimaki, M
Kuh, D
Laakso, M
Liu, YM
Marz, W
Munroe, PB
Njolstad, I
Oostra, BA
Palmer, CNA
Pedersen, NL
Perola, M
Perusse, L
Peters, U
Power, C
Quertermous, T
Rauramaa, R
Rivadeneira, F
Saaristo, TE
Saleheen, D
Sinisalo, J
Slagboom, PE
Snieder, H
Spector, TD
Thorsteinsdottir, UR
Stumvoll, M
Tuomilehto, J
Uitterlinden, AG
Uusitupa, M
van der Harst, P
Veronesi, G
Walker, M
Wareham, NJ
Watkins, H
Wichmann, HE
Abecasis, GR
Assimes, TL
Berndt, SI
Boehnkes, M
Borecki, IB
Deloukas, P
Franke, L
Frayling, TM
Groop, LC
Hunter, DJ
Kaplan, RC
O'Connell, JR
Qi, L
Schlessinger, D
Strachan, DP
Stefansson, K
van Dujin, CM
Willer, CJ
Visscher, PM
Yang, J
Hirschhorn, JN
Zillikens, MC
McCarthy, MI
Speliotes, EK
North, KE
Fox, CS
Barroso, I
Franks, PW
Ingelsson, E
Heid, IM
Loos, RJF
Cupples, LA
Morris, AP
Lindgren, CM
Mohlke, KL
AF Shungin, Dmitry
Winkler, Thomas W.
Croteau-Chonka, Damien C.
Ferreira, Teresa
Lockes, Adam E.
Maegi, Reedik
Strawbridge, Rona J.
Pers, Tune H.
Fischer, Krista
Justice, Anne E.
Workalemahu, Tsegaselassie
Wu, Joseph M. W.
Buchkovich, Martin L.
Heard-Costa, Nancy L.
Roman, Tamara S.
Drong, Alexander W.
Song, Ci
Gustafsson, Stefan
Day, Felix R.
Esko, Tonu
Fall, Tove
Kutalik, Zoltan
Luan, Jian'an
Randall, Joshua C.
Scherag, Andre
Vedantam, Sailaja
Wood, Andrew R.
Chen, Jin
Fehrmann, Rudolf
Karjalainen, Juha
Kahali, Bratati
Liu, Ching-Ti
Schmidt, Ellen M.
Absher, Devin
Amin, Najaf
Anderson, Denise
Beekman, Marian
Bragg-Gresham, Jennifer L.
Buyske, Steven
Demirkan, Ayse
Ehret, Georg B.
Feitosa, Mary F.
Goel, Anuj
Jackson, Anne U.
Johnson, Toby
Kleber, Marcus E.
Kristiansson, Kati
Mangino, Massimo
Leach, Irene Mateo
Medina-Gomez, Carolina
Palmer, Cameron D.
Pasko, Dorota
Pechlivaniss, Sonali
Peters, Marjolein J.
Prokopenko, Inga
Stancakova, Alena
Sung, Yun Ju
Tanakam, Toshiko
Teumer, Alexander
Van Vliet-Ostaptchouk, Jana V.
Yengo, Loic
Zhang, Weihua
Albrecht, Eva
Arnlov, Johan
Arscott, Gillian M.
Bandinelli, Stefania
Barrett, Amy
Bellis, Claire
Bennett, Amanda J.
Berne, Christian
Blueher, Matthias
Buhringer, Stefan
Bonnet, Fabrice
Boettcher, Yvonne
Bruinenberg, Marcel
Carba, Delia B.
Caspersen, Ida H.
Clarke, Robert
Daw, E. Warwick
Deelen, Joris
Deelman, Ewa
Delgado, Graciela
Doney, Alex S. F.
Eklund, Niina
Erdos, Michael R.
Estrada, Karol
Eury, Elodie
Friedrichs, Nele
Garcia, Melissa E.
Giedraitis, Vilmantas
Gigante, Bruna
Go, Alan S.
Golay, Alain
Grallert, Harald
Grammer, Tanja B.
Graessler, Juergen
Grewal, Jagvir
Groves, Christopher J.
Haller, Toomas
Hallmans, Goran
Hartman, Catharina A.
Hassinen, Maija
Hayward, Caroline
Heikkila, Kauko
Herzig, Karl-Heinz
Helmer, Quinta
Hillege, Hans L.
Holmen, Oddgeir
Hunt, Steven C.
Isaacs, Aaron
Ittermann, Till
James, Alan L.
Johansson, Ingegerd
Juliusdottir, Thorhildur
Kalafati, Ioanna-Panagiota
Kinnunen, Leena
Koenig, Wolfgang
Kooner, Ishminder K.
Kratzer, Wolfgang
Lamina, Claudia
Leander, Karin
Lee, Nanette R.
Lichtner, Peter
Lind, Lars
Lindstrom, Jaana
Lobbens, Stephane
Lorentzon, Mattias
Mach, Francois
Magnusson, Patrik K. E.
Mahajan, Anubha
McArdle, Wendy L.
Menni, Cristina
Merger, Sigrun
Mihailov, Evelin
Milani, Lili
Mills, Rebecca
Moayyeri, Alireza
Monda, Ken L.
Mooijaart, Simon P.
Muehleisen, Thomas W.
Mulas, Antonella
Mueller, Gabriele
Mueller-Nurasyid, Martina
Nagaraja, Ramaiah
Nalls, Michael A.
Narisu, Narisu
Glorioso, Nicola
Nolte, Ilja M.
Olden, Matthias
Rayner, Nigel W.
Renstrom, Frida
Ried, Janina S.
Robertson, Neil R.
Rose, Lynda M.
Sanna, Serena
Scharnagl, Hubert
Scholtens, Salome
Sennblad, Bengt
Seufferlein, Thomas
Sitlani, Colleen M.
Smith, Albert Vernon
Stirrups, Kathleen
Stringham, Heather M.
Sundstrom, Johan
Swertz, Morris A.
Swift, Amy J.
Syvanen, Ann-Christine
Tayo, Bamidele O.
Thorand, Barbara
Thorleifsson, Gudmar
Tomaschitz, Andreas
Troffa, Chiara
van Oort, Floor V. A.
Verweij, Niek
Vonk, Judith M.
Waite, Lindsay L.
Wennauer, Roman
Wilsgaard, Tom
Wojczynski, Mary K.
Wong, Andrew
Zhang, Qunyuan
Zhao, Jing Hua
Brennan, Eoin P.
Choi, Murim
Eriksson, Per
Folkersen, Lasse
Franco-Cereceda, Anders
Gharavi, Ali G.
Hedman, Asa K.
Hivert, Marie-France
Huang, Jinyan
Kanoni, Stavroula
Karpe, Fredrik
Keildson, Sarah
Kiryluk, Krzysztof
Liang, Liming
Lifton, Richard P.
Ma, Baoshan
McKnight, Amy J.
McPherson, Ruth
Metspalu, Andres
Min, Josine L.
Moffatt, Miriam F.
Montgomery, Grant W.
Murabito, Joanne M.
Nicholson, George
Nyholt, Dale R.
Olsson, Christian
Perry, John R. B.
Reinmaa, Eva
Salem, Rany M.
Sandholm, Niina
Schadt, Eric E.
Scott, Robert A.
Stolk, Lisette
Vallejo, Edgar E.
Westra, Harm-Jan
Zondervan, Krina T.
Amouyel, Philippe
Arveiler, Dominique
Bakker, Stephan J. L.
Beilby, John
Bergman, Richard N.
Blangero, John
Brown, Morris J.
Burnier, Michel
Campbell, Harry
Chakravarti, Aravinda
Chiness, Peter S.
Claudi-Boehmi, Simone
Collins, Francis S.
Crawford, Dana C.
Danesh, John
de Faire, Ulf
de Geusl, Eco J. C.
Doerr, Marcus
Erbel, Raimund
Eriksson, Johan G.
Farrall, Martin
Ferrannini, Ele
Ferrieres, Jean
Forouhi, Nita G.
Forrester, Terrence
Franco, Oscar H.
Gansevoort, Ron T.
Gieger, Christian
Gudnason, Vilmundur
Haiman, Christopher A.
Harris, Tamara B.
Hattersley, Andrew T.
Heliovaara, Markku
Hicks, Andrew A.
Hingorani, Aroon D.
Hoffmann, Wolfgang
Hofman, Albert
Homuth, Georg
Humphries, Steve E.
Hyppoenen, Elina
Illig, Thomas
Jarvelin, Marjo-Riitta
Johansen, Berit
Jousilahti, Pekka
Jula, Antti M.
Kaprio, Jaakko
Kee, Frank
Keinanen-Kiukaanniemi, Sirkka M.
Kooner, Jaspal S.
Kooperberg, Charles
Kovacs, Peter
Kraja, Aldi T.
Kumari, Meena
Kuulasmaa, Kari
Kuusisto, Johanna
Lakka, Timo A.
Langenberg, Claudia
Le Marchand, Loic
Lehtimaki, Terho
Lyssenko, Valeriya
Mannisto, Satu
Marette, Andre
Matise, Tara C.
McKenzie, Colin A.
McKnight, Barbara
Musk, Arthur W.
Mohlenkamp, Stefan
Morris, Andrew D.
Nelis, Mari
Ohlsson, Claes
Oldehinkel, Albertine J.
Ong, Ken K.
Palmer, Lyle J.
Penninx, Brenda W.
Peters, Annette
Pramstaller, Peter P.
Raitakari, Olli T.
Rankinen, Tuomo
Rao, D. C.
Rice, Treva K.
Ridker, Paul M.
Ritchie, Marylyn D.
Rudan, Igor
Salomaa, Veikko
Samani, Nilesh J.
Saramies, Jouko
Sarzynski, Mark A.
Schwarz, Peter E. H.
Shuldiner, Alan R.
Staessen, Jan A.
Steinthorsdottir, Valgerdur
Stolk, Ronald P.
Strauch, Konstantin
Toenjes, Anke
Tremblay, Angelo
Tremoli, Elena
Vohl, Marie-Claude
Voelker, Uwe
Vollenweider, Peter
Wilson, James F.
Witteman, Jacqueline C.
Adair, Linda S.
Bochud, Murielle
Boehm, Bernhard O.
Bornstein, Stefan R.
Bouchard, Claude
Cauchi, Stephane
Caulfield, Mark J.
Chambers, John C.
Chasman, Daniel I.
Cooper, Richard S.
Dedoussis, George
Ferrucci, Luigi
Froguel, Philippe
Grabe, Hans-Joergen
Hamsten, Anders
Hui, Jennie
Hveem, Kristian
Joeckel, Karl-Heinz
Kivimaki, Mika
Kuh, Diana
Laakso, Markku
Liu, Yongmei
Maerz, Winfried
Munroe, Patricia B.
Njolstad, Inger
Oostra, Ben A.
Palmer, Colin N. A.
Pedersen, Nancy L.
Perola, Markus
Perusse, Louis
Peters, Ulrike
Power, Chris
Quertermous, Thomas
Rauramaa, Rainer
Rivadeneira, Fernando
Saaristo, Timo E.
Saleheen, Danish
Sinisalo, Juha
Slagboom, P. Eline
Snieder, Harold
Spector, Tim D.
Thorsteinsdottir, Unnur R.
Stumvoll, Michael
Tuomilehto, Jaakko
Uitterlinden, Andre G.
Uusitupa, Math
van der Harst, Pim
Veronesi, Giovanni
Walker, Mark
Wareham, Nicholas J.
Watkins, Hugh
Wichmann, H-Erich
Abecasis, Goncalo R.
Assimes, Themistocles L.
Berndt, Sonja I.
Boehnkes, Michael
Borecki, Ingrid B.
Deloukas, Panos
Franke, Lude
Frayling, Timothy M.
Groop, Leif C.
Hunter, David J.
Kaplan, Robert C.
O'Connell, Jeffrey R.
Qi, Lu
Schlessinger, David
Strachan, David P.
Stefansson, Kari
van Dujin, Cornelia M.
Willer, Cristen J.
Visscher, Peter M.
Yang, Jian
Hirschhorn, Joel N.
Zillikens, M. Carola
McCarthy, Mark I.
Speliotes, Elizabeth K.
North, Kari E.
Fox, Caroline S.
Barroso, Ines
Franks, Paul W.
Ingelsson, Erik
Heid, Iris M.
Loos, Ruth J. F.
Cupples, L. Adrienne
Morris, Andrew P.
Lindgren, Cecilia M.
Mohlke, Karen L.
CA ADIPOGEN Consortium
CARDIOGRAMplusC4D Consortium
CKDGen Consortium
GEFOS Consortium
GENIE Consortium
GLGC
ICBP
Int Endogene Consortium
LifeLines Cohort Study
MAGIC Investigators
MuTHER Consortium
PAGE Consortium
ReproGen Consortium
TI New genetic loci link adipose and insulin biology to body fat
distribution
SO NATURE
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; MESENCHYMAL STEM-CELLS; HUMAN HEIGHT;
ADIPOGENIC DIFFERENTIATION; ABDOMINAL ADIPOSITY; SUSCEPTIBILITY LOCI;
SEXUAL-DIMORPHISM; GLYCEMIC TRAITS; FALSE DISCOVERY; COMMON SNPS
AB Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 x 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.
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[McKnight, Amy J.] Queens Univ Belfast, Ctr Publ Hlth, Belfast BT9 7AB, Down, North Ireland.
[McPherson, Ruth] Univ Ottawa, Inst Heart, Ottawa, ON K1Y 4W7, Canada.
[Moffatt, Miriam F.; Kooner, Jaspal S.] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, London SW3 6LY, England.
[Montgomery, Grant W.; Nyholt, Dale R.] QIMR Berghofer Med Res Inst, Brisbane, Qld 4006, Australia.
[Murabito, Joanne M.] Boston Univ, Sch Med, Sect Gen Internal Med, Boston, MA 02118 USA.
[Nicholson, George] Univ Oxford, Dept Stat, Oxford OX1 3TG, England.
[Nicholson, George] MRC Harwell, Harwell OX11 0QG, Berks, England.
[Nyholt, Dale R.] Queensland Univ Technol, Inst Hlth & Biomed Innovat, Brisbane, Qld 4059, Australia.
[Sandholm, Niina] Aalto Univ, Sch Sci, Dept Biomed Engn & Computat Sci, FI-00076 Helsinki, Finland.
[Sandholm, Niina] Univ Helsinki, Cent Hosp, Div Nephrol, Dept Med, FI-00290 Helsinki, Finland.
[Sandholm, Niina] Folkhalsan Inst Genet, Folkhalsan Res Ctr, FI-00290 Helsinki, Finland.
[Schadt, Eric E.] Icahn Sch Med Mt Sinai, Icahn Inst Genom & Multiscale Biol, New York, NY 10580 USA.
[Vallejo, Edgar E.] Tecnol Monterrey, Dept Comp Sci, Atizapan De Zaragoza 52926, Mexico.
[Zondervan, Krina T.] Univ Oxford, Nuffield Dept Obstet & Gynaecol, Oxford OX3 7BN, England.
[Amouyel, Philippe] Univ Lille 2, Inst Pasteur Lille, INSERM, U744, F-59000 Lille, France.
[Arveiler, Dominique] Univ Strasbourg, Fac Med, EA3430, Dept Epidemiol & Publ Hlth, Strasbourg, France.
[Bakker, Stephan J. L.; Gansevoort, Ron T.] Univ Groningen, Univ Med Ctr Groningen, Dept Internal Med, NL-9700 RB Groningen, Netherlands.
[Beilby, John; Hui, Jennie] Univ Western Australia, Perth, WA 6009, Australia.
[Bergman, Richard N.] Cedars Sinai Diabet & Obes Res Inst, Los Angeles, CA 90048 USA.
[Brown, Morris J.] Univ Cambridge, Addenbrookes Hosp, Clin Pharmacol Unit, Cambridge CB2 2QQ, England.
[Burnier, Michel] Lausanne Univ Hosp CHUV, Dept Med, Serv Nephrol, CH-1005 Lausanne, Switzerland.
[Campbell, Harry; Rudan, Igor; Wilson, James F.] Univ Edinburgh, Ctr Populat Hlth Sci, Edinburgh EH8 9AG, Midlothian, Scotland.
[Crawford, Dana C.] Vanderbilt Univ, Med Ctr, Ctr Human Genet Res, Nashville, TN 37203 USA.
[Crawford, Dana C.] Vanderbilt Univ, Dept Mol Physiol & Biophys, Nashville, TN 37232 USA.
[Danesh, John; Saleheen, Danish] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge CB1 8RN, England.
[de Geusl, Eco J. C.] Vrije Univ Amsterdam, NL-1081 BT Amsterdam, Netherlands.
[de Geusl, Eco J. C.; Penninx, Brenda W.] Vrije Univ Amsterdam, Inst Hlth & Care Res, Inst Res Extramural Med, NL-1081 BT Amsterdam, Netherlands.
[Doerr, Marcus] Univ Med Greifswald, Dept Internal Med B, D-17475 Greifswald, Germany.
[Doerr, Marcus; Hoffmann, Wolfgang; Voelker, Uwe] Partner Site Greifswald, DZHK, D-17475 Greifswald, Germany.
[Erbel, Raimund; Mohlenkamp, Stefan] Univ Hosp Essen, West German Heart Ctr, Clin Cardiol, D-45122 Essen, Germany.
[Eriksson, Johan G.] Univ Helsinki, Dept Gen Practice & Primary Hlth, FI-00290 Helsinki, Finland.
[Eriksson, Johan G.] Univ Helsinki, Cent Hosp, Unit Gen Practice, FI-00290 Helsinki, Finland.
[Ferrannini, Ele] Univ Pisa, Dept Internal Med, I-56100 Pisa, Italy.
[Ferrieres, Jean] Toulouse Univ, Sch Med, Rangueil Hosp, Dept Cardiol, F-31400 Toulouse, France.
[Forrester, Terrence; McKenzie, Colin A.] Univ W Indies, UWI Solut Developing Countries, Kingston 7, Jamaica.
[Haiman, Christopher A.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90089 USA.
[Hattersley, Andrew T.] Univ Exeter, Inst Biomed & Clin Sci, Exeter EX2 5DW, Devon, England.
[Hicks, Andrew A.; Pramstaller, Peter P.] Bolzano EURAC, European Acad Bozen, Ctr Biomed, I-39100 Bolzano, Italy.
[Hicks, Andrew A.; Pramstaller, Peter P.] Inst Univ Lubeck, D-23562 Lubeck, Germany.
[Hingorani, Aroon D.] UCL, Inst Cardiovasc Sci, London WC1E 6BT, England.
[Humphries, Steve E.] UCL, Ctr Cardiovasc Genet, Inst Cardiovasc Sci, London WC1E 6JJ, England.
[Hyppoenen, Elina] Univ S Australia, Sansom Inst Hlth Res, Adelaide, SA 5000, Australia.
[Hyppoenen, Elina] Univ S Australia, Sch Populat Hlth, Adelaide, SA 5000, Australia.
[Hyppoenen, Elina] South Australian Hlth & Med Res Inst, Adelaide, SA 5000, Australia.
[Hyppoenen, Elina; Power, Chris] UCL, Inst Child Hlth, London WC1N 1EH, England.
[Illig, Thomas] Hannover Med Sch, Hannover Unified Biobank, D-30625 Hannover, Germany.
[Jarvelin, Marjo-Riitta] Natl Inst Hlth & Welf, FI-90101 Oulu, Finland.
[Jarvelin, Marjo-Riitta] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, MRC Hlth Protect Agcy HPA Ctr Environ & Hlth, London W2 1PG, England.
[Jarvelin, Marjo-Riitta] Oulu Univ Hosp, Unit Primary Care, FI-90014 Oulu, Finland.
[Jarvelin, Marjo-Riitta] Univ Oulu, Inst Hlth Sci, FI-90014 Oulu, Finland.
[Kee, Frank] Queens Univ Belfast, UK Clin Res Collaborat Ctr Excellence Publ Hlth N, Belfast BT7 1NN, Antrim, North Ireland.
[Keinanen-Kiukaanniemi, Sirkka M.] Univ Oulu, Inst Hlth Sci, Fac Med, FI-90014 Oulu, Finland.
[Keinanen-Kiukaanniemi, Sirkka M.] Oulu Univ Hosp, Unit Primary Hlth Care Gen Practice, FI-90220 Oulu, Finland.
[Kooner, Jaspal S.] Imperial Coll Healthcare NHS Trust, London W12 0HS, England.
[Kooperberg, Charles; Peters, Ulrike] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA.
[Kumari, Meena; Langenberg, Claudia; Kivimaki, Mika] UCL, Dept Epidemiol & Publ Hlth, London WC1E 6BT, England.
[Kumari, Meena] Univ Essex, Dept Biol & Social Epidemiol, Colchester CO4 3SQ, Essex, England.
[Kuusisto, Johanna; Laakso, Markku] Kuopio Univ Hosp, Dept Med, FI-70210 Kuopio, Finland.
[Kuusisto, Johanna; Lakka, Timo A.; Laakso, Markku; Rauramaa, Rainer] Univ Eastern Finland, FI-70210 Kuopio, Finland.
[Lakka, Timo A.] Univ Eastern Finland, Inst Biomed, Dept Physiol, FI-70211 Kuopio, Finland.
[Lakka, Timo A.; Rauramaa, Rainer] Kuopio Univ Hosp, Dept Clin Physiol & Nucl Med, FI-70210 Kuopio, Finland.
[Le Marchand, Loic] Univ Hawaii, Ctr Canc, Epidemiol Program, Honolulu, HI 96813 USA.
[Lehtimaki, Terho] Univ Tampere, Fimlab Labs, Dept Clin Chem, FI-33520 Tampere, Finland.
[Lehtimaki, Terho] Univ Tampere, Sch Med, FI-33520 Tampere, Finland.
[Lyssenko, Valeriya] Steno Diabet Ctr AS, DK-2820 Gentofte, Denmark.
[Lyssenko, Valeriya; Groop, Leif C.] Lund Univ, Lund Univ Diabet Ctr, S-22100 Malmo, Sweden.
[Lyssenko, Valeriya; Groop, Leif C.] Lund Univ, Dept Clin Sci, Diabet & Endocrinol Unit, S-22100 Malmo, Sweden.
[Marette, Andre] Univ Laval, Fac Med, Inst Univ Cardiol & Pneumol Quebec, Quebec City, PQ G1V 0A6, Canada.
[Marette, Andre; Vohl, Marie-Claude; Perusse, Louis] Univ Laval, Inst Nutr & Funct Foods, Quebec City, PQ G1V 0A6, Canada.
[Musk, Arthur W.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Musk, Arthur W.] Sir Charles Gairdner Hosp, Dept Resp Med, Nedlands, WA 6009, Australia.
[Palmer, Lyle J.] Univ Toronto, Toronto, ON M5G 1E2, Canada.
[Lakka, Timo A.; Rauramaa, Rainer] Ontario Inst Canc Res, Toronto, ON M5G 0A3, Canada.
[Penninx, Brenda W.] Vrije Univ Amsterdam, Dept Psychiat, NL-1081 BT Amsterdam, Netherlands.
[Pramstaller, Peter P.] Gen Cent Hosp, Dept Neurol, I-39100 Bolzano, Italy.
[Raitakari, Olli T.] Turku Univ Hosp, Dept Clin Physiol & Nucl Med, FI-20521 Turku, Finland.
[Raitakari, Olli T.] Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, FI-20521 Turku, Finland.
[Rankinen, Tuomo; Sarzynski, Mark A.; Bouchard, Claude] Pennington Biomed Res Ctr, Human Genom Lab, Baton Rouge, LA 70808 USA.
[Rao, D. C.; Rice, Treva K.] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA.
[Ritchie, Marylyn D.] Penn State Univ, Ctr Syst Genom, University Pk, PA 16802 USA.
[Rudan, Igor] Univ Split, Croatian Ctr Global Hlth, Fac Med, Split 21000, Croatia.
[Samani, Nilesh J.] Univ Leicester, Glenfield Hosp, Dept Cardiovasc Sci, Leicester LE3 9QP, Leics, England.
[Samani, Nilesh J.] Glenfield Gen Hosp, Natl Inst Hlth Res NIHR Leicester Cardiovasc Biom, Leicester LE3 9QP, Leics, England.
[Saramies, Jouko] South Carelia Cent Hosp, Lappeenranta 53130, Finland.
[Schwarz, Peter E. H.] Paul Langerhans Inst Dresden, German Ctr Diabet Res DZD, D-01307 Dresden, Germany.
[Shuldiner, Alan R.; O'Connell, Jeffrey R.] Univ Maryland, Sch Med, Divis Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA.
[Shuldiner, Alan R.; O'Connell, Jeffrey R.] Univ Maryland, Program Personalized & Genom Med, Sch Med, Baltimore, MD 21201 USA.
[Shuldiner, Alan R.] Vet Adm Med Ctr, Geriatr Res & Educ Clin Ctr, Baltimore, MD 21201 USA.
[Staessen, Jan A.] Maastricht Univ, Dept Epidemiol, NL-6229 HA Maastricht, Netherlands.
[Staessen, Jan A.] Univ Leuven, KU Leuven Dept Cardiovasc Sci, Res Unit Hypertens & Cardiovasc Epidemiol, B-3000 Louvain, Belgium.
[Tremblay, Angelo; Perusse, Louis] Univ Laval, Dept Kinesiol, Quebec City, PQ G1V 0A6, Canada.
[Tremoli, Elena] Univ Milan, Dipartimento Sci Farmacol & Biomol, I-20133 Milan, Italy.
[Tremoli, Elena] Inst Ricovero & Cura Carattere Sci, Ctr Cardiol Monzi, I-20133 Milan, Italy.
[Vohl, Marie-Claude] Univ Laval, Dept Food Sci & Nutr, Quebec City, PQ G1V 0A6, Canada.
[Vollenweider, Peter] Univ Hosp CHUV, Dept Internal Med, CH-1011 Lausanne, Switzerland.
[Vollenweider, Peter; Bochud, Murielle] Univ Lausanne, CH-1011 Lausanne, Switzerland.
[Adair, Linda S.] Univ N Carolina, Dept Nutr, Chapel Hill, NC 27599 USA.
[Bochud, Murielle] CHU Vaudois, Inst Social & Prevent Med IUMSP, CH-1010 Lausanne, Switzerland.
[Boehm, Bernhard O.] Imperial Coll London, Lee Kong Chian Sch Med, Singapore 637553, Singapore.
[Boehm, Bernhard O.] Nanyang Technol Univ, Singapore 637553, Singapore.
[Boehm, Bernhard O.] Univ Ulm, Med Ctr, Dept Internal Med 1, D-89081 Ulm, Germany.
[Caulfield, Mark J.; Munroe, Patricia B.] Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, Dept Clin Pharmacol, London EC1M 6BQ, England.
[Grabe, Hans-Joergen] HELIOS Hosp Stralsund, Univ Med Greifswald, Dept Psychiat & Psychotherapy, D-17475 Greifswald, Germany.
[Grabe, Hans-Joergen] German Ctr Neurodegenerat Dis DZNE, D-17475 Greifswald, Germany.
[Hui, Jennie] Univ Western Australia, Sch Populat Hlth, Nedlands, WA 6009, Australia.
[Liu, Yongmei] Wake Forest Sch Med, Div Publ Hlth Sci, Ctr Human Genet, Winston Salem, NC 27157 USA.
[Maerz, Winfried] Synlab Serv GmbH, Synlab Acad, D-68163 Mannheim, Germany.
[Oostra, Ben A.] Erasmus MC Univ Med Ctr, Dept Clin Genet, NL-3000 CA Rotterdam, Netherlands.
[Quertermous, Thomas; Assimes, Themistocles L.] Stanford Univ, Sch Med, Dept Med, Palo Alto, CA 94304 USA.
[Saaristo, Timo E.] Finnish Diabet Assoc, FI-33680 Tampere, Finland.
[Saaristo, Timo E.] Pirkanmaa Hosp Dist, FI-33521 Tampere, Finland.
[Saleheen, Danish] Ctr Noncommunicable Dis, Karatchi, Pakistan.
[Saleheen, Danish] Univ Penn, Dept Med, Philadelphia, PA 19104 USA.
[Sinisalo, Juha] Univ Helsinki, Cent Hosp, Heart & Lung Ctr, Dept Med, FI-00290 Helsinki, Finland.
[Thorsteinsdottir, Unnur R.; Stefansson, Kari] Univ Iceland, Fac Med, IS-101 Reykjavik, Iceland.
[Tuomilehto, Jaakko] Hosp Univ LaPaz IdiPAZ, Inst Invest Sanitaria, Madrid 28046, Spain.
[Tuomilehto, Jaakko] King Abdulaziz Univ, Diabet Res Grp, Jeddah 21589, Saudi Arabia.
[Tuomilehto, Jaakko] Danube Univ Krems, Ctr Vasc Prevent, A-3500 Krems, Austria.
[Uusitupa, Math] Univ Eastern Finland, Dept Publ Hlth & Clin Nutr, FI-70211 Kuopio, Finland.
[van der Harst, Pim] Interuniv Cardiol Inst Netherlands, Netherlands Heart Inst, Durrer Ctr Cardiogenet Res, NL-3501 DG Utrecht, Netherlands.
[Veronesi, Giovanni] Univ Insubria, EPIMED Res Ctr, Dept Clin & Expt Med, I-21100 Varese, Italy.
[Walker, Mark] Newcastle Univ, Inst Cellular Med, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England.
[Wichmann, H-Erich] Univ Munich, Chair Epidemiol, Inst Med Informat Biometry & Epidemiol, D-85764 Munich, Germany.
[Wichmann, H-Erich] Klinikum Grosshadern, D-81377 Munich, Germany.
[Wichmann, H-Erich] Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Epidemiol 1, D-85764 Neuherberg, Germany.
[Berndt, Sonja I.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Deloukas, Panos] King Abdulaziz Univ, Princess Al Jawhara Al Brahim Ctr Excellence Res, Jeddah 21589, Saudi Arabia.
[Kaplan, Robert C.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10461 USA.
[Strachan, David P.] St Georges Univ London, Div Populat Hlth Sci & Educ, London SW17 0RE, England.
[Willer, Cristen J.] Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA.
[Visscher, Peter M.; Yang, Jian] Univ Queensland, Queensland Brain Inst, Brisbane, Qld 4072, Australia.
[Visscher, Peter M.; Yang, Jian] Univ Queensland, Diamantina Inst, Translat Res Inst, Brisbane, Qld 4012, Australia.
[McCarthy, Mark I.] Oxford Univ Hosp NHS Trust, Oxford NIHR Biomed Res Ctr, Oxford OX3 7LJ, England.
[North, Kari E.] Univ N Carolina, Carolina Ctr Genome Sci, Chapel Hill, NC 27599 USA.
[Barroso, Ines] Univ Cambridge, Metab Res Labs, Inst Metab Sci, Addenbrookes Hosp, Cambridge CB2 OQQ, England.
[Barroso, Ines] Addenbrookes Hosp, Inst Metab Sci, NIHR Cambridge Biomed Res Ctr, Cambridge CB2 OQQ, England.
[Loos, Ruth J. F.] Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA.
[Loos, Ruth J. F.] Icahn Sch Med Mt Sinai, Genet Obes & Related Metab Traits Program, New York, NY 10029 USA.
[Loos, Ruth J. F.] Icahn Sch Med Mt Sinai, Mindich Child Hlth & Dev Inst, New York, NY 10029 USA.
[Morris, Andrew P.] Univ Liverpool, Dept Biostat, Liverpool L69 3GA, Merseyside, England.
RP Mohlke, KL (reprint author), Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA.
EM celi@well.ox.ac.uk; mohlke@med.unc.edu
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Grant/0000-0002-4140-8139; Rivadeneira, Fernando/0000-0001-9435-9441;
Prokopenko, Inga/0000-0003-1624-7457
FU British Heart Foundation [FS/14/55/30806, RG/08/008/25291,
RG/08/014/24067, RG/10/12/28456, RG/13/2/30098]; Cancer Research UK
[14136]; Chief Scientist Office [CZB/4/710]; Diabetes UK [12/0004470];
Intramural NIH HHS [Z01 HG000024-14]; Medical Research Council
[G1000143, G0401527, G0601261, G0601463, G1001799, G9521010,
MC_PC_U127561128, MC_U106179471, MC_U106179472, MC_UP_A100_1003,
MC_UP_A620_1014, MC_UU_12011/1, MC_UU_12012/1, MC_UU_12013/1,
MC_UU_12015/1, MC_UU_12015/2, MC_UU_12015/5, MC_UU_12019/1,
MR/K006584/1, MR/K011480/1, MR/K013351/1, MR/L003120/1, MR/N01104X/1];
NCI NIH HHS [UM1 CA182910, UM1 CA182913]; NHGRI NIH HHS [U01 HG007376,
U01 HG007416, U01 HG007419]; NHLBI NIH HHS [K01 HL116770, R00 HL094535,
R01 HL109946, R01 HL117078, R01 HL117626, T32 HL007055, T32 HL069768];
NIA NIH HHS [R01 AG025941, R01 AG033193, R01 AG041517, U01 AG049505];
NIDA NIH HHS [R21 DA027040]; NIDDK NIH HHS [K23 DK080145, P30 DK020541,
P30 DK020572, P30 DK040561, P30 DK072488, P30 DK079637, P60 DK020541,
R01 DK062370, R01 DK072193, R01 DK075787, R01 DK078150, R01 DK089256,
R01 DK093757, R01 DK107437, U01 DK062370]; NIGMS NIH HHS [P30 GM103341,
T32 GM007092, T32 GM067553]; NIMHD NIH HHS [P20 MD006899]; Wellcome
Trust [084766, 085235, 097117, 098017, 098381, 098498, 100574]
NR 95
TC 165
Z9 166
U1 34
U2 215
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 FEB 12
PY 2015
VL 518
IS 7538
BP 187
EP U378
DI 10.1038/nature14132
PG 22
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CA8SD
UT WOS:000349190300030
PM 25673412
ER
PT J
AU Locke, AE
Kahali, B
Berndt, SI
Justice, AE
Pers, TH
Felix, R
Powell, C
Vedantam, S
Buchkovich, ML
Yang, J
Croteau-Chonka, DC
Esko, T
Fall, T
Ferreira, T
Gustafsson, S
Kutalik, Z
Luan, JA
Magi, R
Randall, JC
Winkler, TW
Wood, AR
Workalemahu, T
Faul, JD
Smith, JA
Zhao, JH
Zhao, W
Chen, J
Fehrmann, R
Hedman, AK
Karjalainen, J
Schmidt, EM
Absher, D
Amin, N
Anderson, D
Beekman, M
Bolton, JL
Bragg-Gresham, L
Buyske, S
Demirkan, A
Deng, GH
Ehret, GB
Feenstra, B
Feitosa, MF
Fischer, K
Goel, A
Gong, J
Jackson, AU
Kanoni, S
Kleber, ME
Kristiansson, K
Lim, U
Lotay, V
Mangino, M
Leach, IM
Medina-Gomez, C
Medland, SE
Nalls, MA
Palmer, CD
Pasko, D
Pechlivanis, S
Peters, MJ
Prokopenko, I
Shungin, D
Stancakova, A
Strawbridge, RJ
Sung, YJ
Tanaka, T
Teumer, A
Trompet, S
van der Laan, SW
van Settee, J
Van Vliet-Ostaptchouk, JV
Wang, ZM
Yengo, L
Zhang, WH
Isaacs, A
Albrecht, E
Arnlov, J
Arscott, GM
Attwood, AP
Bandinelli, S
Barrett, A
Bas, IN
Bellis, C
Bennett, AJ
Berne, C
Blagieva, R
Bluher, M
Bohringer, S
Bonnycastle, LL
Bottcher, Y
Boyd, HA
Bruinenberg, M
Caspersen, IH
Chen, YD
Clarke, R
Daw, EW
de Craen, AJM
Delgado, G
Dimitriou, M
Doney, ASF
Eklund, N
Estrada, K
Eury, E
Folkersen, L
Fraser, RM
Garcia, ME
Geller, F
Giedraitis, V
Gigante, B
Go, AS
Golay, A
Goodall, AH
Gordon, SD
Gorski, M
Grabe, HJ
Grallert, H
Grammer, TB
Grassler, J
Gronberg, H
Groves, CJ
Gusto, G
Haessler, J
Hall, P
Haller, T
Hallmans, G
Hartman, CA
Hassinen, M
Hayward, C
Heard-Costa, NL
Helmer, Q
Hengstenberg, C
Holmen, O
Hottenga, JJ
James, AL
Jeff, JM
Johansson, A
Jolley, J
Juliusdottir, T
Kinnunen, L
Koenig, W
Koskenvuo, M
Kratzer, W
Laitinen, J
Lamina, C
Leander, K
Lee, NR
Lichtner, P
Lind, L
Lindstrom, J
Lo, KS
Lobbens, S
Lorbeer, R
Lu, YC
Mach, F
Magnusson, PKE
Mahajan, A
McArdle, WL
McLachlan, S
Menni, C
Merger, S
Mihailov, E
Milani, L
Moayyeri, A
Monda, KL
Morken, MA
Mulas, A
Muller, G
Muller-Nurasyid, M
Musk, AW
Nagaraja, R
Nothen, MM
Nolte, IM
Pilz, S
Rayner, NW
Renstrom, F
Rettig, R
Ried, JS
Ripke, S
Robertson, NR
Rose, LM
Sanna, S
Scharnagl, H
Scholtens, S
Schumacher, FR
Scott, WR
Seufferlein, T
Shi, JX
Smith, AV
Smolonska, J
Stanton, AV
Steinthorsdottir, V
Stirrups, K
Stringham, HM
Sundstrom, J
Swertz, MA
Swift, AJ
Syvanen, AC
Tan, ST
Tayo, BO
Thorand, B
Thorleifsson, G
Tyrer, JP
Uh, HW
Vandenput, L
Verhulst, FC
Vermeulen, SH
Verweij, N
Vonk, JM
Waite, LL
Warren, HR
Waterworth, D
Weedon, MN
Wilkens, LR
Willenborg, C
Wilsgaard, T
Wojczynski, MK
Wong, A
Wrightl, AF
Zhang, QY
Brennan, EP
Choi, M
Dastani, Z
Drong, AW
Eriksson, P
Franco-Cereceda, A
Gadin, JR
Gharavi, AG
Goddard, ME
Handsaker, RE
Huang, JY
Karpe, F
Kathiresan, S
Keildson, S
Kiryluk, K
Kubo, M
Lee, JY
Liang, L
Lifton, RP
Ma, BS
McCarroll, SA
McKnight, AJ
Min, JL
Moffatt, MF
Montgomery, GW
Murabito, JM
Nicholson, G
Nyholt, DR
Okada, Y
Perry, JRB
Dorajoo, R
Reinmaa, E
Salem, RM
Sandholm, N
Scott, RA
Stolk, L
Takahashi, A
Tanaka, T
van 't Hooft, FM
Vinkhuyzen, AAE
Westra, HJ
Zheng, W
Zondervan, KT
Heath, AC
Arveiler, D
Bakker, SJL
Beilby, J
Bergman, RN
Blangero, J
Bovet, P
Campbell, H
Caulfield, MJ
Cesana, G
Chakravarti, A
Chasman, DI
Chines, PS
Collins, FS
Crawford, DC
Cupples, LA
Cusi, D
Danesh, J
de Faire, U
den Ruijter, HM
Dominiczak, AF
Erbel, R
Erdmann, J
Eriksson, JG
Farrall, M
Felix, SB
Ferrannini, E
Ferrieres, J
Ford, I
Forouhi, NG
Forrester, T
Franco, OH
Gansevoort, RT
Gejman, PV
Gieger, C
Gottesman, O
Gudnason, V
Gyllensten, U
Hall, AS
Harris, TB
Hattersley, AT
Hicks, AA
Hindorff, LA
Hingorani, AD
Hofman, A
Homuth, G
Hovingh, GK
Humphries, SE
Hunt, SC
Hypponen, E
Illig, T
Jacobs, KB
Jarvelin, MR
Jockel, KH
Johansen, B
Jousilahti, P
Jukema, JW
Jula, AM
Kaprio, J
Kastelein, JJP
Keinanen-Kiukaanniemi, SM
Kiemeney, LA
Knekt, P
Kooner, JS
Kooperberg, C
Kovacs, P
Kraja, AT
Kumari, M
Kuusisto, J
Lakka, TA
Langenberg, C
Le Marchand, L
Lehtimaki, T
Lyssenko, V
Mannisto, S
Marette, A
Matise, TC
McKenzie, CA
McKnight, B
Moll, FL
Morris, AD
Morris, AP
Murray, JC
Nelis, M
Ohlsson, C
Oldehinkel, AJ
Ong, KK
Madden, PAF
Pasterkamp, G
Peden, JF
Peters, A
Postma, DS
Pramstaller, PP
Price, JF
Qi, L
Raitakari, OT
Rankinen, T
Rao, DC
Rice, TK
Ridker, PM
Rioux, JD
Ritchie, MD
Rudan, I
Salomaa, V
Samani, NJ
Saramines, J
Sarzynski, MA
Schunkert, H
Schwarz, PEH
Sever, P
Shuldiner, AR
Sinisalo, J
Stolk, RP
Strauch, K
Tonjes, A
Tregouet, DA
Tremblay, A
Tremoli, E
Virtamo, J
Vohl, MC
Volker, U
Waeber, G
Willemsen, G
Witteman, JC
Zillikens, MC
Adair, LS
Amouyel, P
Asselbergs, FW
Assimes, TL
Bochud, M
Boehm, BO
Boerwinkle, E
Bornstein, SR
Bottinger, EP
Bouchard, C
Cauchi, S
Chambers, JC
Chanock, SJ
Cooper, RS
de Bakker, PIW
Dedoussis, G
Ferrucci, L
Franks, PW
Froguel, P
Groop, LC
Haiman, CA
Hamsten, A
Hui, JN
Hunter, DJ
Hveem, K
Kaplan, RC
Kivimaki, M
Kuh, D
Laakso, M
Liu, YM
Martin, NG
Marz, W
Melbve, M
Metspalu, A
Moebus, S
Munroe, PB
Njolstad, I
Oostra, BA
Palmer, CNA
Pedersen, NL
Perola, M
Perusse, L
Peters, U
Power, C
Quertermous, T
Rauramaa, R
Rivadeneira, F
Saaristo, TE
Saleheen, D
Sattar, N
Schadt, EE
Schlessinger, D
Slagboom, PE
Snieder, H
Spector, TD
Thorsteinsdottir, UR
Stumvoll, M
Tuomilehto, J
Uitterlinden, AG
Uusitupa, M
van der Harst, P
Walker, M
Wallaschofski, H
Wareham, NJ
Watkins, H
Weir, DR
Wichmann, HE
Wilson, JF
Zanen, P
Borecki, IB
Deloukas, P
Fox, CS
Heid, IM
O'Connell, JR
Strachan, DP
Stefansson, K
van Duijri, CM
Abecasis, GR
Franke, L
Frayling, TM
McCarthy, MI
Visscher, PM
Scherag, A
Willer, CJ
Boehnke, M
Mohlke, KL
Lindgren, CM
Beckmann, JS
Barroso, I
North, KE
Ingelsson, E
Hirschhorn, JN
Loos, RJF
Speliotes, EK
AF Locke, Adam E.
Kahali, Bratati
Berndt, Sonja I.
Justice, Anne E.
Pers, Tune H.
Day, Felix R.
Powell, Corey
Vedantam, Sailaja
Buchkovich, Martin L.
Yang, Jian
Croteau-Chonka, Damien C.
Esko, Tonu
Fall, Tove
Ferreira, Teresa
Gustafsson, Stefan
Kutalik, Zoltan
Luan, Jian'an
Maegi, Reedik
Randall, Joshua C.
Winkler, Thomas W.
Wood, Andrew R.
Workalemahu, Tsegaselassie
Faul, Jessica D.
Smith, Jennifer A.
Zhao, Jing Hua
Zhao, Wei
Chen, Jin
Fehrmann, Rudolf
Hedman, Asa K.
Karjalainen, Juha
Schmidt, Ellen M.
Absher, Devin
Amin, Najaf
Anderson, Denise
Beekman, Marian
Bolton, Jennifer L.
Bragg-Gresham, L.
Buyske, Steven
Demirkan, Ayse
Deng, Guohong
Ehret, Georg B.
Feenstra, Bjarke
Feitosa, Mary F.
Fischer, Krista
Goel, Anuj
Gong, Jian
Jackson, Anne U.
Kanoni, Stavroula
Kleber, Marcus E.
Kristiansson, Kati
Lim, Unhee
Lotay, Vaneet
Mangino, Massimo
Leach, Irene Mateo
Medina-Gomez, Carolina
Medland, Sarah E.
Nalls, Michael A.
Palmer, Cameron D.
Pasko, Dorota
Pechlivanis, Sonali
Peters, Marjolein J.
Prokopenko, Inga
Shungin, Dmitry
Stancakova, Alena
Strawbridge, Rona J.
Sung, Yun Ju
Tanaka, Toshiko
Teumer, Alexander
Trompet, Stella
van der Laan, Sander W.
van Settee, Jessica
Van Vliet-Ostaptchouk, Jana V.
Wang, Zhaoming
Yengo, Loic
Zhang, Weihua
Isaacs, Aaron
Albrecht, Eva
Arnlov, Johan
Arscott, Gillian M.
Attwood, Antony P.
Bandinelli, Stefania
Barrett, Amy
Bas, Isabelita N.
Bellis, Claire
Bennett, Amanda J.
Berne, Christian
Blagieva, Roza
Blueher, Matthias
Bohringer, Stefan
Bonnycastle, Lori L.
Boettcher, Yvonne
Boyd, Heather A.
Bruinenberg, Marcel
Caspersen, Ida H.
Chen, Yii-Der Ida
Clarke, Robert
Daw, E. Warwick
de Craen, Anton J. M.
Delgado, Graciela
Dimitriou, Maria
Doney, Alex S. F.
Eklund, Niina
Estrada, Karol
Eury, Elodie
Folkersen, Lasse
Fraser, Ross M.
Garcia, Melissa E.
Geller, Frank
Giedraitis, Vilmantas
Gigante, Bruna
Go, Alan S.
Golay, Alain
Goodall, Alison H.
Gordon, Scott D.
Gorski, Mathias
Grabe, Hans-Joergen
Grallert, Harald
Grammer, Tanja B.
Graessler, Jurgen
Gronberg, Henrik
Groves, Christopher J.
Gusto, Gaeelle
Haessler, Jeffrey
Hall, Per
Haller, Toomas
Hallmans, Goran
Hartman, Catharina A.
Hassinen, Maija
Hayward, Caroline
Heard-Costa, Nancy L.
Helmer, Qinta
Hengstenberg, Christian
Holmen, Oddgeir
Hottenga, Jouke-Jan
James, Alan L.
Jeff, Janina M.
Johansson, Asa
Jolley, Jennifer
Juliusdottir, Thorhildur
Kinnunen, Leena
Koenig, Wolfgang
Koskenvuo, Markku
Kratzer, Wolfgang
Laitinen, Jaana
Lamina, Claudia
Leander, Karin
Lee, Nanette R.
Lichtner, Peter
Lind, Lars
Lindstrom, Jaana
Lo, Ken Sin
Lobbens, Stephane
Lorbeer, Roberto
Lu, Yingchang
Mach, Francois
Magnusson, Patrik K. E.
Mahajan, Anubha
McArdle, Wendy L.
McLachlan, Stela
Menni, Cristina
Merger, Sigrun
Mihailov, Evelin
Milani, Lili
Moayyeri, Alireza
Monda, Keri L.
Morken, Mario A.
Mulas, Antonella
Mueller, Gabriele
Mueller-Nurasyid, Martina
Musk, Arthur W.
Nagaraja, Ramaiah
Noethen, Markus M.
Nolte, Ilja M.
Pilz, Stefan
Rayner, Nigel W.
Renstrom, Frida
Rettig, Rainer
Ried, Janina S.
Ripke, Stephan
Robertson, Neil R.
Rose, Lynda M.
Sanna, Serena
Scharnagl, Hubert
Scholtens, Salome
Schumacher, Fredrick R.
Scott, William R.
Seufferlein, Thomas
Shi, Jianxin
Smith, Albert Vernon
Smolonska, Joanna
Stanton, Alice V.
Steinthorsdottir, Valgerdur
Stirrups, Kathleen
Stringham, Heather M.
Sundstrom, Johan
Swertz, Morris A.
Swift, Amy J.
Syvanen, Ann-Christine
Tan, Sian-Tsung
Tayo, Bamidele O.
Thorand, Barbara
Thorleifsson, Gudmar
Tyrer, Jonathan P.
Uh, Hae-Won
Vandenput, Liesbeth
Verhulst, Frank C.
Vermeulen, Sita H.
Verweij, Niek
Vonk, Judith M.
Waite, Lindsay L.
Warren, Helen R.
Waterworth, Dawn
Weedon, Michael N.
Wilkens, Lynne R.
Willenborg, Christina
Wilsgaard, Tom
Wojczynski, Mary K.
Wong, Andrew
Wrightl, Alan F.
Zhang, Qunyuan
Brennan, Eoin P.
Choi, Murim
Dastani, Zari
Drong, Alexander W.
Eriksson, Per
Franco-Cereceda, Anders
Gadin, Jesper R.
Gharavi, Ali G.
Goddard, Michael E.
Handsaker, Robert E.
Huang, Jinyan
Karpe, Fredrik
Kathiresan, Sekar
Keildson, Sarah
Kiryluk, Krzysztof
Kubo, Michiaki
Lee, Jong-Young
Liang, Liming
Lifton, Richard P.
Ma, Baoshan
McCarroll, Steven A.
McKnight, Amy J.
Min, Josine L.
Moffatt, Miriam F.
Montgomery, Grant W.
Murabito, Joanne M.
Nicholson, George
Nyholt, Dale R.
Okada, Yukinori
Perry, John R. B.
Dorajoo, Rajkumar
Reinmaa, Eva
Salem, Rany M.
Sandholm, Niina
Scott, Robert A.
Stolk, Lisette
Takahashi, Atsushi
Tanaka, Toshihiro
van 't Hooft, Ferdinand M.
Vinkhuyzen, Anna A. E.
Westra, Harm-Jan
Zheng, Wei
Zondervan, Krina T.
Heath, Andrew C.
Arveiler, Dominique
Bakker, Stephan J. L.
Beilby, John
Bergman, Richard N.
Blangero, John
Bovet, Pascal
Campbell, Harry
Caulfield, Mark J.
Cesana, Giancarlo
Chakravarti, Aravinda
Chasman, Daniel I.
Chines, Peter S.
Collins, Francis S.
Crawford, Dana C.
Cupples, L. Adrienne
Cusi, Daniele
Danesh, John
de Faire, Ulf
den Ruijter, Hester M.
Dominiczak, Anna F.
Erbel, Raimund
Erdmann, Jeanette
Eriksson, Johan G.
Farrall, Martin
Felix, Stephan B.
Ferrannini, Ele
Ferrieres, Jean
Ford, Ian
Forouhi, Nita G.
Forrester, Terrence
Franco, Oscar H.
Gansevoort, Ron T.
Gejman, Pablo V.
Gieger, Christian
Gottesman, Omri
Gudnason, Vilmundur
Gyllensten, Ulf
Hall, Alistair S.
Harris, Tamara B.
Hattersley, Andrew T.
Hicks, Andrew A.
Hindorff, Lucia A.
Hingorani, Aroon D.
Hofman, Albert
Homuth, Georg
Hovingh, G. Kees
Humphries, Steve E.
Hunt, Steven C.
Hypponen, Elina
Illig, Thomas
Jacobs, Kevin B.
Jarvelin, Marjo-Riitta
Joeckel, Karl-Heinz
Johansen, Berit
Jousilahti, Pekka
Jukema, J. Wouter
Jula, Antti M.
Kaprio, Jaakko
Kastelein, John J. P.
Keinanen-Kiukaanniemi, Sirkka M.
Kiemeney, Lambertus A.
Knekt, Paul
Kooner, Jaspal S.
Kooperberg, Charles
Kovacs, Peter
Kraja, Aldi T.
Kumari, Meena
Kuusisto, Johanna
Lakka, Timo A.
Langenberg, Claudia
Le Marchand, Laic
Lehtimaki, Terho
Lyssenko, Valeriya
Mannisto, Satu
Marette, Andre
Matise, Tara C.
McKenzie, Colin A.
McKnight, Barbara
Moll, Frans L.
Morris, Andrew D.
Morris, Andrew P.
Murray, Jeffrey C.
Nelis, Mari
Ohlsson, Claes
Oldehinkel, Albertine J.
Ong, Ken K.
Madden, Pamela A. F.
Pasterkamp, Gerard
Peden, John F.
Peters, Annette
Postma, Dirkje S.
Pramstaller, Peter P.
Price, Jackie F.
Qi, Lu
Raitakari, Olli T.
Rankinen, Tuomo
Rao, D. C.
Rice, Treva K.
Ridker, Paul M.
Rioux, John D.
Ritchie, Marylyn D.
Rudan, Igor
Salomaa, Veikko
Samani, Nilesh J.
Saramines, Jouko
Sarzynski, Mark A.
Schunkert, Heribert
Schwarz, Peter E. H.
Sever, Peter
Shuldiner, Alan R.
Sinisalo, Juha
Stolk, Ronald P.
Strauch, Konstantin
Toenjes, Anke
Tregouet, David-Alexandre
Tremblay, Angelo
Tremoli, Elena
Virtamo, Jarmo
Vohl, Marie-Claude
Voelker, Uwe
Waeber, Gerard
Willemsen, Gonneke
Witteman, Jacqueline C.
Zillikens, M. Carola
Adair, Linda S.
Amouyel, Philippe
Asselbergs, Folkert W.
Assimes, Themistocles L.
Bochud, Murielle
Boehm, Bernhard O.
Boerwinkle, Eric
Bornstein, Stefan R.
Bottinger, Erwin P.
Bouchard, Claude
Cauchi, Stephane
Chambers, John C.
Chanock, Stephen J.
Cooper, Richard S.
de Bakker, Paul I. W.
Dedoussis, George
Ferrucci, Luigi
Franks, Paul W.
Froguel, Philippe
Groop, Leif C.
Haiman, Christopher A.
Hamsten, Anders
Hui, Jennie
Hunter, David J.
Hveem, Kristian
Kaplan, Robert C.
Kivimaki, Mika
Kuh, Diana
Laakso, Markku
Liu, Yongmei
Martin, Nicholas G.
Maerz, Winfried
Melbve, Mads
Metspalu, Andres
Moebus, Susanne
Munroe, Patricia B.
Njolstad, Inger
Oostra, Ben A.
Palmer, Colin N. A.
Pedersen, Nancy L.
Perola, Markus
Perusse, Louis
Peters, Ulrike
Power, Chris
Quertermous, Thomas
Rauramaa, Rainer
Rivadeneira, Fernando
Saaristo, Timo E.
Saleheen, Danish
Sattar, Naveed
Schadt, Eric E.
Schlessinger, David
Slagboom, P. Eline
Snieder, Harold
Spector, Tim D.
Thorsteinsdottir, Unnu R.
Stumvoll, Michael
Tuomilehto, Jaakko
Uitterlinden, Andre G.
Uusitupa, Matti
van der Harst, Pim
Walker, Mark
Wallaschofski, Henri
Wareham, Nicholas J.
Watkins, Hugh
Weir, David R.
Wichmann, H-Erich
Wilson, James F.
Zanen, Pieter
Borecki, Ingrid B.
Deloukas, Panos
Fox, Caroline S.
Heid, Iris M.
O'Connell, Jeffrey R.
Strachan, David P.
Stefansson, Kari
van Duijri, Cornelia M.
Abecasis, Goncalo R.
Franke, Lude
Frayling, Timothy M.
McCarthy, Mark I.
Visscher, Peter M.
Scherag, Andre
Willer, Cristen J.
Boehnke, Michael
Mohlke, Karen L.
Lindgren, Cecilia M.
Beckmann, Jacques S.
Barroso, Ines
North, Kari E.
Ingelsson, Erik
Hirschhorn, Joel N.
Loos, Ruth J. F.
Speliotes, Elizabeth K.
CA LifeLines Cohort Study
ADIPOGen Consortium
AGEN-BMI Working Grp
CARDIOGRAMplusC4D Consortium
CKDGen Consortium
GLGC
ICBP
MAGIC Investigators
MuTHER Consortium
MIGen Consortium
PAGE Consortium
ReproGen Consortium
GENIE Consortium
Int Endogene Consortium
TI Genetic studies of body mass index yield new insights for obesity
biology
SO NATURE
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; PROVIDES INSIGHTS; GLYCEMIC TRAITS; HUMAN
HEIGHT; LOCI; METAANALYSIS; VARIANTS; EXPRESSION; PATHWAYS; ARCHITECTURE
AB Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in upto 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 x 10(-8)), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for similar to 2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous systemin obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.
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[Kahali, Bratati; Powell, Corey; Speliotes, Elizabeth K.] Univ Michigan, Dept Internal Med, Div Gastroenterol, Ann Arbor, MI 48109 USA.
[Kahali, Bratati; Powell, Corey; Speliotes, Elizabeth K.] Univ Michigan, Dept Computat Med & Bioinformat, Ann Arbor, MI 48109 USA.
[Berndt, Sonja I.; Wang, Zhaoming; Jacobs, Kevin B.; Chanock, Stephen J.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
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[Pers, Tune H.; Vedantam, Sailaja; Esko, Tonu; Palmer, Cameron D.; Salem, Rany M.; Hirschhorn, Joel N.] Boston Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA.
[Pers, Tune H.; Vedantam, Sailaja; Esko, Tonu; Palmer, Cameron D.; Salem, Rany M.; Hirschhorn, Joel N.] Boston Childrens Hosp, Div Genet, Boston, MA 02115 USA.
[Pers, Tune H.; Vedantam, Sailaja; Esko, Tonu; Palmer, Cameron D.; Salem, Rany M.; Hirschhorn, Joel N.] Boston Childrens Hosp, Ctr Basic & Translat Obes Res, Boston, MA 02115 USA.
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[Pers, Tune H.] Tech Univ Denmark, Dept Syst Biol, Ctr Biol Sequence Anal, DK-2800 Lyngby, Denmark.
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[Buchkovich, Martin L.; Croteau-Chonka, Damien C.; Mohlke, Karen L.] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA.
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[James, Alan L.] Dept Pulm Physiol & Sleep Med, Nedlands, WA 6009, Australia.
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[Koskenvuo, Markku; Kaprio, Jaakko] Univ Helsinki, Dept Publ Hlth, Hjelt Inst, FI-00014 Helsinki, Finland.
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[Lichtner, Peter] Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Inst Human Genet, D-85764 Neuherberg, Germany.
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[Lorbeer, Roberto] Univ Med Greifswald, Inst Community Med, D-17475 Greifswald, Germany.
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[Mihailov, Evelin; Metspalu, Andres] Univ Tartu, Inst Mol & Cell Biol, EE-51010 Tartu, Estonia.
[Moayyeri, Alireza] UCL, Farr Inst Hlth Informat Res, London NW1 2DA, England.
[Monda, Keri L.] Amgen Inc, Ctr Observat Res, Newbury Pk, CA 91320 USA.
[Mulas, Antonella; Sanna, Serena] CNR, IRGB, I-09042 Cagliari, Sardinia, Italy.
[Mueller, Gabriele] Tech Univ Dresden, Univ Hosp Carl Gustav Carus, Ctr Evidence Based Healthcare, D-01307 Dresden, Germany.
[Mueller-Nurasyid, Martina] Univ Munich, Univ Hosp Grosshadern, Dept Med 1, D-81377 Munich, Germany.
[Mueller-Nurasyid, Martina; Strauch, Konstantin] Univ Munich, Chair Genet Epidemiol, Inst Med Informat Biometry & Epidemiol, D-81377 Munich, Germany.
[Musk, Arthur W.] Sir Charles Gairdner Hosp, Dept Resp Med, Nedlands, WA 6009, Australia.
[Nagaraja, Ramaiah; Schlessinger, David] NIA, Lab Genet, Baltimore, MD 21224 USA.
[Noethen, Markus M.] Univ Bonn, Life & Brain Ctr, Dept Genom, D-53127 Bonn, Germany.
[Noethen, Markus M.] Univ Bonn, Inst Human Genet, D-53127 Bonn, Germany.
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[Lyssenko, Valeriya; Groop, Leif C.] Lund Univ, Lund Univ Diabet Ctr, S-22100 Malmo, Sweden.
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RP Speliotes, EK (reprint author), Univ Michigan, Dept Internal Med, Div Gastroenterol, Ann Arbor, MI 48109 USA.
EM joelh@broadinstitute.org; ruth.loos@mssm.edu; espeliot@med.umich.edu
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John/A-9599-2015; Onland-Moret, N. Charlotte/G-9185-2011; Gudnason,
Vilmundur/K-6885-2015; Huang, Jiaxing/B-7521-2009; Ripatti,
Samuli/H-9446-2014; Mattace- Raso, Francesco/L-2541-2015; Wilson, James
F/A-5704-2009; Polasek, Ozren/B-6002-2011; Montgomery,
Grant/B-7148-2008; Singleton, Andrew/C-3010-2009; Moayyeri,
Alireza/N-3332-2014; Palmer, Colin/C-7053-2008; Boehm,
Bernhard/F-8750-2015; Fehrmann, Rudolf/E-2551-2011; Colaus,
PsyColaus/K-6607-2013; Grallert, Harald/B-3424-2013; Fall,
Tove/O-7226-2014; Kiemeney, Lambertus/D-3357-2009; de Bakker,
Paul/B-8730-2009; Meisinger, Christine/B-5358-2014; Visser, Jenny
/F-8156-2011
OI Wain, Louise/0000-0003-4951-1867; Medland, Sarah/0000-0003-1382-380X;
Kaprio, Jaakko/0000-0002-3716-2455; Lawlor, Debbie
A/0000-0002-6793-2262; Hattersley, Andrew/0000-0001-5620-473X; Sinisalo,
Juha/0000-0002-0169-5137; Lahti, Jari/0000-0002-4310-5297; Kleber,
Marcus/0000-0003-0663-7275; Ganna, Andrea/0000-0002-8147-240X; Peters,
Annette/0000-0001-6645-0985; Medina-Gomez, Carolina/0000-0001-7999-5538;
Visscher, Peter/0000-0002-2143-8760; Marmot,
Michael/0000-0002-2431-6419; Eriksson, Johan/0000-0002-2516-2060;
Prabhakaran, Dorairaj/0000-0002-3172-834X; Falhammar,
Henrik/0000-0002-5622-6987; Evans, David/0000-0003-0663-4621; Assimes,
Themistocles/0000-0003-2349-0009; Ouwehand, Willem/0000-0002-7744-1790;
Folkersen, Lasse/0000-0003-0708-9530; Smith,
Jennifer/0000-0002-3575-5468; ruggiero, daniela/0000-0003-3898-7827;
Buyske, Steven/0000-0001-8539-5416; Vandenput,
Liesbeth/0000-0002-1712-6131; Karpe, Fredrik/0000-0002-2751-1770;
Maxwell, Alexander P./0000-0002-6110-7253; Vinkhuyzen,
Anna/0000-0003-3352-0603; Ramos , Rafel/0000-0001-7970-5537; Kumari,
Meena/0000-0001-9716-1035; Verweij, Niek/0000-0002-4303-7685; Kuulasmaa,
Kari/0000-0003-2165-1411; Karasik, David/0000-0002-8826-0530; Hedman,
Asa/0000-0001-5413-204X; Wolffenbuttel, Bruce H.R./0000-0001-9262-6921;
Forouhi, Nita/0000-0002-5041-248X; Jarvelin,
Marjo-Riitta/0000-0002-2149-0630; rossing, peter/0000-0002-1531-4294;
Nothen, Markus/0000-0002-8770-2464; Goessling,
Wolfram/0000-0001-9972-1569; Mannisto, Satu/0000-0002-8668-3046; Lakka,
Timo/0000-0002-9199-2871; Gigante, Bruna/0000-0003-4508-7990; van der
Laan, Sander W./0000-0001-6888-1404; Humphries, Stephen
E/0000-0002-8221-6547; Adeyemo, Adebowale/0000-0002-3105-3231; Org,
Elin/0000-0003-1451-9375; Esko, Tonu/0000-0003-1982-6569; Arora,
Pankaj/0000-0003-2420-3550; Hosseini, Mohsen/0000-0003-3626-9928;
Sandholm, Niina/0000-0003-4322-6942; Kristiansson,
Kati/0000-0003-4688-107X; Tryggvadottir, Laufey/0000-0001-8067-9030;
Locke, Adam/0000-0001-6227-198X; Gieger, Christian/0000-0001-6986-9554;
Strawbridge, Rona/0000-0001-8506-3585; Menni,
Cristina/0000-0001-9790-0571; Goddard, Michael/0000-0001-9917-7946;
Melzer, David/0000-0002-0170-3838; TREMOLI, ELENA/0000-0002-0929-6106;
Magi, Reedik/0000-0002-2964-6011; Fuchsberger,
Christian/0000-0002-5918-8947; Mulas, Antonella/0000-0002-6856-1483; van
Vliet-Ostaptchouk, Jana/0000-0002-7943-3153; Fraser,
Ross/0000-0003-0488-2592; Beckmann, Jacques S /0000-0002-9741-1900;
Leander, Karin/0000-0002-1404-9222; Yengo, Loic/0000-0002-4272-9305;
Palmer, Lyle/0000-0002-1628-3055; Kolcic, Ivana/0000-0001-7918-6052;
Stathopoulou, Maria/0000-0003-4376-2083; Feitosa,
Mary/0000-0002-0933-2410; Hicks, Andrew/0000-0001-6320-0411; Franks,
Paul/0000-0002-0520-7604; McCarroll, Steven/0000-0002-6954-8184;
Beekman, Marian/0000-0003-0585-6206; Stanton, Alice/0000-0002-4961-165X;
Schwarz, Peter/0000-0001-6317-7880; Ramos , Rafel/0000-0001-8146-5288;
Franke, Lude/0000-0002-5159-8802; Laan, Maris/0000-0002-8519-243X;
Slagboom, P. Eline/0000-0002-2875-4723; Erdmann,
Jeanette/0000-0002-4486-6231; Franke, Andre/0000-0003-1530-5811; Day,
Felix/0000-0003-3789-7651; Asselta, Rosanna/0000-0001-5351-0619;
Seshadri, Sudha/0000-0001-6135-2622; Bush, William/0000-0002-9729-6519;
Peters, Marjolein/0000-0003-3167-9063; Zgaga, Lina/0000-0003-4089-9703;
Shungin, Dmitry/0000-0001-7900-5856; Johansson, Asa/0000-0002-2915-4498;
Bovet, Pascal/0000-0002-0242-4259; Smith, Albert/0000-0003-1942-5845;
Nato, Alejandro/0000-0002-8745-9046; Yang, Jian/0000-0003-2001-2474;
Deloukas, Panos/0000-0001-9251-070X; kinnunen,
leena/0000-0001-8739-4812; Bochud, Murielle/0000-0002-5727-0218;
mangino, massimo/0000-0002-2167-7470; Rivadeneira,
Fernando/0000-0001-9435-9441; Prokopenko, Inga/0000-0003-1624-7457;
Kronenberg, Florian/0000-0003-2229-1120; Sundstrom,
Johan/0000-0003-2247-8454; Tanaka, Toshihiro/0000-0001-6201-9784;
Thorand, Barbara/0000-0002-8416-6440; Lyytikainen,
Leo-Pekka/0000-0002-7200-5455; Hypponen, Elina/0000-0003-3670-9399;
Salumets, Andres/0000-0002-1251-8160; Bakker,
Stephan/0000-0003-3356-6791; Rioux, John/0000-0001-7560-8326; Gudnason,
Vilmundur/0000-0001-5696-0084; Ripatti, Samuli/0000-0002-0504-1202;
Wilson, James F/0000-0001-5751-9178; Polasek, Ozren/0000-0002-5765-1862;
Montgomery, Grant/0000-0002-4140-8139; Moayyeri,
Alireza/0000-0002-9143-2161; Palmer, Colin/0000-0002-6415-6560;
Fehrmann, Rudolf/0000-0002-7516-315X; Kiemeney,
Lambertus/0000-0002-2368-1326; de Bakker, Paul/0000-0001-7735-7858;
FU British Heart Foundation [FS/14/55/30806, RG/08/008/25291,
RG/08/014/24067, RG/10/12/28456]; Cancer Research UK [14136]; Chief
Scientist Office [CZB/4/672, CZB/4/710]; Medical Research Council
[G0401527, G0601261, G1000143, G1001799, G9521010, MC_PC_U127561128,
MC_U106179471, MC_U106179472, MC_UP_A100_1003, MC_UU_12012/1,
MC_UU_12013/1, MC_UU_12015/1, MC_UU_12015/2, MC_UU_12015/5,
MC_UU_12019/1, MR/K006584/1, MR/K013351/1, MR/L003120/1, MR/N01104X/1];
NCATS NIH HHS [TL1 TR001066, UL1 TR000124, UL1 TR001067]; NCI NIH HHS
[UM1 CA182910, UM1 CA182913]; NHGRI NIH HHS [U01 HG007376, U01 HG007416,
U01 HG007419]; NHLBI NIH HHS [K01 HL116770, P30 HL107251, R01 HL109946,
R01 HL117078, R01 HL117626, T32 HL007055, T32 HL007824]; NIA NIH HHS
[R01 AG033193, R01 AG025941, R01 AG041517, U01 AG009740, U01 AG049505];
NIDA NIH HHS [R21 DA027040]; NIDDK NIH HHS [K23 DK080145, P30 DK020541,
P30 DK020572, P30 DK063491, P30 DK072488, P60 DK020541, R01 DK062370,
R01 DK072193, R01 DK075787, R01 DK078150, R01 DK089256, R01 DK093757,
U01 DK062370]; NIGMS NIH HHS [P30 GM103341, T32 GM080178]; NIMHD NIH HHS
[P20 MD006899]; NINDS NIH HHS [R01 NS017950]; Wellcome Trust [084766,
085235, 097117, 098017, 098381, 100574]
NR 73
TC 431
Z9 435
U1 64
U2 323
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 FEB 12
PY 2015
VL 518
IS 7538
BP 197
EP U401
DI 10.1038/nature14177
PG 23
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CA8SD
UT WOS:000349190300031
PM 25673413
ER
PT J
AU Chen, YH
Du, WL
Hagemeijer, MC
Takvorian, PM
Pau, C
Cali, A
Brantner, CA
Stempinski, ES
Connelly, PS
Ma, HC
Jiang, P
Wimmer, E
Altan-Bonnet, G
Altan-Bonnet, N
AF Chen, Ying-Han
Du, WenLi
Hagemeijer, Marne C.
Takvorian, Peter M.
Pau, Cyrilla
Cali, Ann
Brantner, Christine A.
Stempinski, Erin S.
Connelly, Patricia S.
Ma, Hsin-Chieh
Jiang, Ping
Wimmer, Eckard
Altan-Bonnet, Gregoire
Altan-Bonnet, Nihal
TI Phosphatidylserine Vesicles Enable Efficient En Bloc Transmission of
Enteroviruses
SO CELL
LA English
DT Article
ID CELLULAR MEMBRANES; VIRUS ENTRY; ANNEXIN-V; POLIOVIRUS; PROTEIN; CELLS;
REPLICATION; RECOGNITION; MACROPINOCYTOSIS; AUTOPHAGOSOMES
AB A central paradigm within virology is that each viral particle largely behaves as an independent infectious unit. Here, we demonstrate that clusters of enteroviral particles are packaged within phosphatidylserine (PS) lipid-enriched vesicles that are non-lytically released from cells and provide greater infection efficiency than free single viral particles. We show that vesicular PS lipids are co-factors to the relevant enterovirus receptors in mediating subsequent infectivity and transmission, in particular to primary human macrophages. We demonstrate that clustered packaging of viral particles within vesicles enables multiple viral RNA genomes to be collectively transferred into single cells. This study reveals a novel mode of viral transmission, where enteroviral genomes are transmitted from cell-to-cell en bloc in membrane-bound PS vesicles instead of as single independent genomes. This has implications for facilitating genetic cooperativity among viral quasispecies as well as enhancing viral replication.
C1 [Chen, Ying-Han; Du, WenLi; Hagemeijer, Marne C.; Altan-Bonnet, Nihal] NHLBI, Lab Host Pathogen Dynam, NIH, Bethesda, MD 20892 USA.
[Chen, Ying-Han; Takvorian, Peter M.; Pau, Cyrilla; Cali, Ann] Rutgers State Univ, Federated Dept Biol Sci, Newark, NJ 07102 USA.
[Brantner, Christine A.; Stempinski, Erin S.; Connelly, Patricia S.] NHLBI, Electron Microscopy Core Facil, NIH, Bethesda, MD 20892 USA.
[Ma, Hsin-Chieh; Jiang, Ping; Wimmer, Eckard] SUNY Stony Brook, Dept Mol Genet & Microbiol, Stony Brook, NY 11794 USA.
[Altan-Bonnet, Gregoire] Mem Sloan Kettering Canc Ctr, Program Computat Biol & Immunol, New York, NY 10065 USA.
RP Altan-Bonnet, N (reprint author), NHLBI, Lab Host Pathogen Dynam, NIH, Bethesda, MD 20892 USA.
EM nihal.altan-bonnet@nih.gov
OI Brantner, Christine/0000-0001-8172-901X
FU NIH; [AI091985-01A1]; [AI083408]; [AI15122]
FX The authors would like to thank Yasmine Belkaid, Konstantin Chumakov,
Ana Maria Cuervo, James Hogle, Gerald Feldman, Jennifer Jones, Jennifer
Lippincott-Schwartz, Sanford Simon, Radek Dobrowolski, Wilma Friedman,
Ellie Ehrenfeld and members of the Altan-Bonnet lab for fruitful
discussions. The authors would like to especially thank Wen-Chin Tseng
for help in constructing the graphical cartoons. The authors also thank
Frank Macaluso and Geoffrey Perumal of the Albert Einstein College of
Medicine Analytical Imaging facility for technical support. A.C., P.T.,
and C.P. were supported by grant AI091985-01A1; G.A.B. was supported by
grant AI083408; H.M., P.J., and E.W. were supported by grant AI15122;
and Y.C., W.D., M.H., C.B., P.C., E.S., and N.A.B. were supported by
intramural NIH funds.
NR 49
TC 38
Z9 38
U1 2
U2 17
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 FEB 12
PY 2015
VL 160
IS 4
BP 619
EP 630
DI 10.1016/j.cell.2015.01.032
PG 12
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA CA8ZE
UT WOS:000349208800007
PM 25679758
ER
PT J
AU McDermott, DH
Gao, JL
Liu, Q
Siwicki, M
Martens, C
Jacobs, P
Velez, D
Yim, E
Bryke, CR
Hsu, N
Dai, ZY
Marquesen, MM
Stregevsky, E
Kwatemaa, N
Theobald, N
Priel, DAL
Pittaluga, S
Raffeld, MA
Calvo, KR
Maric, I
Desmond, R
Holmes, KL
Kuhns, DB
Balabanian, K
Bachelerie, F
Porcella, SF
Malech, HL
Murphy, PM
AF McDermott, David H.
Gao, Ji-Liang
Liu, Qian
Siwicki, Marie
Martens, Craig
Jacobs, Paejonette
Velez, Daniel
Yim, Erin
Bryke, Christine R.
Hsu, Nancy
Dai, Zunyan
Marquesen, Martha M.
Stregevsky, Elina
Kwatemaa, Nana
Theobald, Narda
Priel, Debra A. Long
Pittaluga, Stefania
Raffeld, Mark A.
Calvo, Katherine R.
Maric, Irina
Desmond, Ronan
Holmes, Kevin L.
Kuhns, Douglas B.
Balabanian, Karl
Bachelerie, Francoise
Porcella, Stephen F.
Malech, Harry L.
Murphy, Philip M.
TI Chromothriptic Cure of WHIM Syndrome
SO CELL
LA English
DT Article
ID CXCR4 ANTAGONIST PLERIXAFOR; CHEMOKINE RECEPTORS; HEMATOPOIETIC STEM;
PROGENITOR CELLS; IN-VIVO; MYELOKATHEXIS; SURVIVAL/ANTIAPOPTOSIS;
HYPOGAMMAGLOBULINEMIA; GRANULOCYTOPENIA; DESENSITIZATION
AB Chromothripsis is a catastrophic cellular event recently described in cancer in which chromosomes undergo massive deletion and rearrangement. Here, we report a case in which chromothripsis spontaneously cured a patient with WHIM syndrome, an autosomal dominant combined immunodeficiency disease caused by gain-of-function mutation of the chemokine receptor CXCR4. In this patient, deletion of the disease allele, CXCR4(R334X), as well as 163 other genes from one copy of chromosome 2 occurred in a hematopoietic stem cell (HSC) that re-populated the myeloid but not the lymphoid lineage. In competitive mouse bone marrow (BM) transplantation experiments, Cxcr4 haploinsufficiency was sufficient to confer a strong long-term engraftment advantage of donor BM over BM from either wildtype or WHIM syndrome model mice, suggesting a potential mechanism for the patient's cure. Our findings suggest that partial inactivation of CXCR4 may have general utility as a strategy to promote HSC engraftment in transplantation.
C1 [McDermott, David H.; Gao, Ji-Liang; Liu, Qian; Siwicki, Marie; Jacobs, Paejonette; Velez, Daniel; Yim, Erin; Murphy, Philip M.] NIAID, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA.
[Martens, Craig; Porcella, Stephen F.] NIAID, Res Technol Branch, NIH, Hamilton, MT 59840 USA.
[Stregevsky, Elina; Holmes, Kevin L.] NIAID, Res Technol Branch, NIH, Bethesda, MD 20892 USA.
[Hsu, Nancy; Dai, Zunyan] Quest Diagnost, Chantilly, VA 20151 USA.
[Marquesen, Martha M.; Kwatemaa, Nana; Theobald, Narda; Malech, Harry L.] NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA.
[Priel, Debra A. Long; Kuhns, Douglas B.] Frederick Natl Lab Canc Res, Leidos Biomed Res, Clin Serv Program, Frederick, MD 21701 USA.
[Pittaluga, Stefania; Raffeld, Mark A.] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Calvo, Katherine R.; Maric, Irina] NIH, Div Lab Med, Ctr Clin, Bethesda, MD 20892 USA.
[Desmond, Ronan] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
[Desmond, Ronan] Tallaght Hosp, Dept Haematol, Dublin 24, Ireland.
[Balabanian, Karl; Bachelerie, Francoise] Univ Paris 11, Lab Excellence Res Medicat & Innovat Therapeut, INSERM UMR S996, F-92140 Clamart, France.
[Bryke, Christine R.; Hsu, Nancy] Beth Israel Deaconess Med Ctr, Dept Cytogenet, Boston, MA 02215 USA.
[Dai, Zunyan] Emory Univ, Sch Med, Dept Human Genet, Decatur, GA 30030 USA.
RP Murphy, PM (reprint author), NIAID, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA.
EM pmm@nih.gov
RI Balabanian, Karl/I-2990-2016; BACHELERIE, FRANCOISE/F-8823-2013;
OI McDermott, David/0000-0001-6978-0867; Malech, Harry/0000-0001-5874-5775
FU Division of Intramural Research (DIR) of the National Institute of
Allergy and Infectious Diseases (NIAID), NIH; National Cancer Institute,
NIH [HHSN261200800001E]
FX This work was supported by the Division of Intramural Research (DIR) of
the National Institute of Allergy and Infectious Diseases (NIAID), NIH
and was funded in part with federal funds from the National Cancer
Institute, NIH under contract HHSN261200800001E. We thank Hongwei Zhang
for flow cytometry advice, Carolyn Boscia for help with graphics, and
the research subjects for their participation in the study. A
provisional patent on CXCR4 knockdown as a method to enhance HSC
engraftment has been filed by the US government with D. H. M., Q. L., M.
S., J.G., H. L. M., and P. M. M. as inventors.
NR 34
TC 31
Z9 32
U1 1
U2 19
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 FEB 12
PY 2015
VL 160
IS 4
BP 686
EP 699
DI 10.1016/j.cell.2015.01.014
PG 14
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA CA8ZE
UT WOS:000349208800012
PM 25662009
ER
PT J
AU Lutskiy, MY
Avneri-Katz, S
Zhu, N
Itsko, M
Ronen, Z
Arnusch, CJ
Kasher, R
AF Lutskiy, Marina-Yamit
Avneri-Katz, Shani
Zhu, Ni
Itsko, Mark
Ronen, Zeev
Arnusch, Christopher J.
Kasher, Roni
TI A microbiology-based assay for quantification of bacterial early stage
biofilm formation on reverse-osmosis and nanofiltration membranes
SO SEPARATION AND PURIFICATION TECHNOLOGY
LA English
DT Article
DE Biofilm-growth; Reverse-osmosis; Nanofiltration; Biofouling; Bacterial
initial attachment
ID TECHNOLOGY; ADHESION
AB Membrane-based water treatment and purification technologies are crucial globally, and are especially essential in areas that suffer from a shortage of water. In the source water bacteria are ubiquitous and "microbial attachment and growth on membranes is a major problem associated with these technologies. Here we describe an assay to quantify early stage biofilm growth on reverse-osmosis (RO) and nanofiltration (NF) polyamide membranes. The adherence and growth of Klebsiella oxytoca on RO and NF membranes was monitored over time under static conditions, with repeated removal of planktonic bacteria, and this assay was effective in showing especially the early stages of bacterial attachment and growth. Comparison of bacterial growth on NF270, SW30, TM820-400, and LE-400 membranes showed only slight differences, and in all cases the bacterial growth rate accelerated between 5 and 10 h of incubation time. The average surface growth rate was 1.3 x 10(6) CFU/(cm(2) x h) during 5-10 h of incubation, and was measured by counting colony-forming units (CFU) after detachment of bacteria from the membranes. Fluorescence microscopy confirmed early stage biofilm growth between 5 and 10 h of incubation time. This assay will be useful to assess the susceptibility of membranes to bacterial attachment and subsequent biofilm growth and will be especially useful in screening novel antimicrobial and anti-biofilm membrane coatings and modifications and gaining insight into the mode of action of surface-tethered antimicrobial agents. Since initial irreversible adhesion is a critical step in the development of biofilms and hence biofouling on membranes, a deeper understanding of the process may lead to novel strategies for biofilm prevention. (C) 2014 Elsevier B.V. All rights reserved.
C1 [Lutskiy, Marina-Yamit; Avneri-Katz, Shani; Zhu, Ni; Itsko, Mark; Arnusch, Christopher J.; Kasher, Roni] Ben Gurion Univ Negev, Jacob Blaustein Inst Desert Res, Zuckerberg Inst Water Res, Dept Desalinat & Water Treatment, IL-84990 Sede Boqer, Israel.
[Itsko, Mark] Natl Inst Environm Hlth Sci, Mol Genet Lab, Res Triangle Pk, NC 27709 USA.
[Ronen, Zeev] Ben Gurion Univ Negev, Jacob Blaustein Inst Desert Res, Zuckerberg Inst Water Res, Dept Hydrol & Environm Microbiol, IL-84990 Sede Boqer, Israel.
RP Kasher, R (reprint author), Ben Gurion Univ Negev, Jacob Blaustein Inst Desert Res, Zuckerberg Inst Water Res, Dept Desalinat & Water Treatment, Sde Boqer Campus, IL-84990 Sede Boqer, Israel.
EM kasher@bgu.ac.il
FU Massachusetts Institute of Technology - BenGurion University (MIT-BGU);
Israeli Ministry of Science and Technology for the fellowship of
Advancement of Women in Science [3-8736]; Water Authority of Israel
FX The authors wish to thank the Water Authority of Israel for providing
the 2012-2013 PhD student fellowship Grant (M.-Y.L.). The authors thank
the Massachusetts Institute of Technology - BenGurion University
(MIT-BGU) student exchange program for financing a scholarship and
travel expenses (N.Z.), and the Israeli Ministry of Science and
Technology for the 2012 fellowship of Advancement of Women in Science
(No. 3-8736, M.-Y.L.). The authors thank Dr. Ehud Banin (Bar-Ilan
University, Israel) and Dr. Moshe Herzberg (Ben-Gurion University of the
Negev, Israel) for fruitful scientific discussions.
NR 26
TC 5
Z9 5
U1 2
U2 33
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1383-5866
EI 1873-3794
J9 SEP PURIF TECHNOL
JI Sep. Purif. Technol.
PD FEB 12
PY 2015
VL 141
BP 214
EP 220
DI 10.1016/j.seppur.2014.12.003
PG 7
WC Engineering, Chemical
SC Engineering
GA CA9WE
UT WOS:000349274700026
ER
PT J
AU Carter, BD
Abnet, CC
Feskanich, D
Freedman, ND
Hartge, P
Lewis, CE
Ockene, JK
Prentice, RL
Speizer, FE
Thun, MJ
Jacobs, EJ
AF Carter, Brian D.
Abnet, Christian C.
Feskanich, Diane
Freedman, Neal D.
Hartge, Patricia
Lewis, Cora E.
Ockene, Judith K.
Prentice, Ross L.
Speizer, Frank E.
Thun, Michael J.
Jacobs, Eric J.
TI Smoking and Mortality - Beyond Established Causes
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID BREAST-CANCER RISK; CIGARETTE-SMOKING; PROSTATE-CANCER; PROSPECTIVE
COHORT; NURSES HEALTH; RENAL-FAILURE; UNITED-STATES; ASSOCIATION;
ALCOHOL; DISEASE
AB BACKGROUND
Mortality among current smokers is 2 to 3 times as high as that among persons who never smoked. Most of this excess mortality is believed to be explained by 21 common diseases that have been formally established as caused by cigarette smoking and are included in official estimates of smoking-attributable mortality in the United States. However, if smoking causes additional diseases, these official estimates may significantly underestimate the number of deaths attributable to smoking.
METHODS
We pooled data from five contemporary U.S. cohort studies including 421,378 men and 532,651 women 55 years of age or older. Participants were followed from 2000 through 2011, and relative risks and 95% confidence intervals were estimated with the use of Cox proportional-hazards models adjusted for age, race, educational level, daily alcohol consumption, and cohort.
RESULTS
During the follow-up period, there were 181,377 deaths, including 16,475 among current smokers. Overall, approximately 17% of the excess mortality among current smokers was due to associations with causes that are not currently established as attributable to smoking. These included associations between current smoking and deaths from renal failure (relative risk, 2.0; 95% confidence interval [CI], 1.7 to 2.3), intestinal ischemia (relative risk, 6.0; 95% CI, 4.5 to 8.1), hypertensive heart disease (relative risk, 2.4; 95% CI, 1.9 to 3.0), infections (relative risk, 2.3; 95% CI, 2.0 to 2.7), various respiratory diseases (relative risk, 2.0; 95% CI, 1.6 to 2.4), breast cancer (relative risk, 1.3; 95% CI, 1.2 to 1.5), and prostate cancer (relative risk, 1.4; 95% CI, 1.2 to 1.7). Among former smokers, the relative risk for each of these outcomes declined as the number of years since quitting increased.
CONCLUSIONS
A substantial portion of the excess mortality among current smokers between 2000 and 2011 was due to associations with diseases that have not been formally established as caused by smoking. These associations should be investigated further and, when appropriate, taken into account when the mortality burden of smoking is investigated. (Funded by the American Cancer Society.)
C1 [Carter, Brian D.; Thun, Michael J.; Jacobs, Eric J.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30303 USA.
[Abnet, Christian C.; Freedman, Neal D.; Hartge, Patricia] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Feskanich, Diane; Speizer, Frank E.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA.
[Feskanich, Diane; Speizer, Frank E.] Harvard Univ, Sch Med, Boston, MA USA.
[Lewis, Cora E.] Univ Alabama Birmingham, Dept Med, Div Prevent Med, Birmingham, AL USA.
[Ockene, Judith K.] Univ Massachusetts, Sch Med, Dept Med, Div Prevent & Behav Med, Worcester, MA USA.
[Prentice, Ross L.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA.
RP Carter, BD (reprint author), Amer Canc Soc, Natl Home Off, 250 Williams St NW, Atlanta, GA 30303 USA.
EM brian.carter@cancer.org
RI Freedman, Neal/B-9741-2015; Abnet, Christian/C-4111-2015
OI Freedman, Neal/0000-0003-0074-1098; Abnet, Christian/0000-0002-3008-7843
FU American Cancer Society
FX Funded by the American Cancer Society.
NR 37
TC 115
Z9 117
U1 7
U2 52
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
EI 1533-4406
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD FEB 12
PY 2015
VL 372
IS 7
BP 631
EP 640
DI 10.1056/NEJMsa1407211
PG 10
WC Medicine, General & Internal
SC General & Internal Medicine
GA CA8CK
UT WOS:000349143900007
PM 25671255
ER
PT J
AU Tao-Cheng, JH
Pham, A
Yang, Y
Winters, CA
Gallant, PE
Reese, TS
AF Tao-Cheng, J. -H.
Pham, A.
Yang, Y.
Winters, C. A.
Gallant, P. E.
Reese, T. S.
TI SYNTAXIN 4 IS CONCENTRATED ON PLASMA MEMBRANE OF ASTROCYTES
SO NEUROSCIENCE
LA English
DT Article
DE syntaxin 4; syntaxin 1; exocytosis; electron microscopy; synapse;
astroglia
ID PROTEIN EXPRESSION; GLUTAMATE RELEASE; FUSION; SNARE; TRAFFICKING;
VESICLES; SNAP-25; IMMUNOGOLD; TRANSPORT; NEURONS
AB Syntaxins are a family of transmembrane proteins that participate in SNARE complexes to mediate membrane fusion events including exocytosis. Different syntaxins are thought to participate in exocytosis in different compartments of the nervous system such as the axon, the soma/dendrites or astrocytes. It is well known that exocytosis of synaptic vesicles at axonal presynaptic terminals involves syntaxin 1 but distributions of syntaxins on neuronal somal and dendritic, postsynaptic or astroglial plasma membranes are less well characterized. Here, we use pre-embedding immunogold labeling to compare the distribution of two plasma membrane-enriched syntaxins (1 and 4) in dissociated rat hippocampal cultures as well as in perfusion-fixed mouse brains. Comparison of Western blots of neuronal cultures, consisting of a mixture of hippocampal neurons and glia, with glial cultures, consisting of mostly astrocytes, shows that syntaxin 1 is enriched in neuronal cultures, whereas syntaxin 4 is enriched in glial cultures. Electron microscopy (EM)-immunogold labeling shows that syntaxin 1 is most abundant at the plasma membranes of axons and terminals, while syntaxin 4 is most abundant at astroglial plasma membranes. This differential distribution was evident even at close appositions of membranes at synapses, where syntaxin 1 was localized to the plasma membrane of the presynaptic terminal, including that at the active zone, while syntaxin 4 was localized to nearby peri-synaptic astroglial processes. These results show that syntaxin 4 is available to support exocytosis in astroglia. Published by Elsevier Ltd. on behalf of IBRO.
C1 [Tao-Cheng, J. -H.] NINDS, EM Facil, NIH, Bethesda, MD 20892 USA.
[Pham, A.; Yang, Y.; Winters, C. A.; Gallant, P. E.; Reese, T. S.] NINDS, Neurobiol Lab, NIH, Bethesda, MD 20892 USA.
RP Tao-Cheng, JH (reprint author), 49 Convent Dr,Room 3A50, Bethesda, MD 20892 USA.
EM chengs@ninds.nih.gov
FU NIH, NINDS
FX We thank Virginia Crocker and Rita Azzam for expert EM technical
support, and Dr. Ayse Dosemeci for helpful discussions. Supported by the
Intramural Research Program of the NIH, NINDS.
NR 33
TC 2
Z9 2
U1 0
U2 6
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0306-4522
EI 1873-7544
J9 NEUROSCIENCE
JI Neuroscience
PD FEB 12
PY 2015
VL 286
BP 264
EP 271
DI 10.1016/j.neuroscience.2014.11.054
PG 8
WC Neurosciences
SC Neurosciences & Neurology
GA AZ1YL
UT WOS:000348031200023
PM 25485479
ER
PT J
AU Miller, CA
Hsu, LY
Ta, A
Conn, H
Winkler, S
Arai, AE
AF Miller, Christopher A.
Hsu, Li-Yueh
Ta, Allison
Conn, Hannah
Winkler, Susanne
Arai, Andrew E.
TI Quantitative pixel-wise measurement of myocardial blood flow: The impact
of surface coil-related field inhomogeneity and a comparison of methods
for its correction
SO JOURNAL OF CARDIOVASCULAR MAGNETIC RESONANCE
LA English
DT Article
DE Cardiovascular magnetic resonance; Perfusion; Myocardial blood flow;
Quantification; Field inhomogeneity; Surface coil intensity correction
ID CARDIAC MAGNETIC-RESONANCE; CORONARY-ARTERY-DISEASE; INTENSITY
CORRECTION; PERFUSION ANALYSIS; PHASED-ARRAY; MRI; QUANTIFICATION;
HUMANS; ACCURACY; IMAGES
AB Background: Surface coil-related field inhomogeneity potentially confounds pixel-wise quantitative analysis of perfusion CMR images. This study assessed the effect of surface coil-related field inhomogeneity on the spatial variation of pixel-wise myocardial blood flow (MBF), and assessed its impact on the ability of MBF quantification to differentiate ischaemic from remote coronary territories. Two surface coil intensity correction (SCIC) techniques were evaluated: 1) a proton density-based technique (PD-SCIC) and; 2) a saturation recovery steady-state free precession-based technique (SSFP-SCIC).
Methods: 26 subjects (18 with significant CAD and 8 healthy volunteers) underwent stress perfusion CMR using a motion-corrected, saturation recovery SSFP dual-sequence protocol. A proton density (PD)-weighted image was acquired at the beginning of the sequence. Surface coil-related field inhomogeneity was approximated using a third-order surface fit to the PD image or a pre-contrast saturation prepared SSFP image. The estimated intensity bias field was subsequently applied to the image series. Pixel-wise MBF was measured from mid-ventricular stress images using the two SCIC approaches and compared to measurements made without SCIC.
Results: MBF heterogeneity in healthy volunteers was higher using SSFP-SCIC (24.8 +/- 4.1%) compared to PD-SCIC (20.8 +/- 3.0%; p = 0.009), however heterogeneity was significantly lower using either SCIC technique compared to analysis performed without SCIC (36.2 +/- 6.3%). In CAD patients, the difference in MBF between remote and ischaemic territories was minimal when analysis was performed without SCIC (0.06 +/- 0.91 mL/min/kg), and was substantially lower than with either PD-SCIC (0.50 +/- 0.63 mL/min/kg; p = 0.013) or with SSFP-SCIC (0.63 +/- 0.89 mL/min/kg; p = 0.005). In 6 patients, MBF quantified without SCIC was artifactually higher in the stenosed coronary territory compared to the remote territory. PD-SCIC and SSFP-SCIC had similar differences in MBF between remote and ischaemic territories (p = 0.145).
Conclusions: This study demonstrates that surface coil-related field inhomogeneity can confound pixel-wise MBF quantification. Whilst a PD-based SCIC led to a more homogenous correction than a saturation recovery SSFP-based technique, this did not result in an appreciable difference in the differentiation of ischaemic from remote coronary territories and thus either method could be applied.
C1 [Miller, Christopher A.; Hsu, Li-Yueh; Ta, Allison; Conn, Hannah; Winkler, Susanne; Arai, Andrew E.] NHLBI, Dept Hlth & Human Serv, Adv Cardiovasc Imaging Lab, NIH, Bethesda, MD 20892 USA.
RP Arai, AE (reprint author), NHLBI, Dept Hlth & Human Serv, Adv Cardiovasc Imaging Lab, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM araia@nih.gov
FU National Institute for Health Research, UK [NIHR-DRF-2010-03-98]
FX CAM was supported by a Fellowship from the National Institute for Health
Research, UK (NIHR-DRF-2010-03-98).
NR 19
TC 1
Z9 1
U1 0
U2 3
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 FEB 11
PY 2015
VL 17
AR 11
DI 10.1186/s12968-015-0117-1
PG 9
WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical
Imaging
SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine &
Medical Imaging
GA CB9IP
UT WOS:000349945500002
PM 25827156
ER
PT J
AU Costa, VD
Tran, VL
Turchi, J
Averbeck, BB
AF Costa, Vincent D.
Tran, Valery L.
Turchi, Janita
Averbeck, Bruno B.
TI Reversal Learning and Dopamine: A Bayesian Perspective
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE Bayesian; dopamine; haloperidol; L-DOPA; reinforcement learning;
reversal learning
ID PREFRONTAL CORTEX; PARKINSONS-DISEASE; ORBITOFRONTAL CORTEX;
NUCLEUS-ACCUMBENS; FRONTAL-CORTEX; IN-VIVO; LESIONS; DISCRIMINATION;
REINFORCEMENT; SENSITIVITY
AB Reversal learning has been studied as the process of learning to inhibit previously rewarded actions. Deficits in reversal learning have been seen after manipulations of dopamine and lesions of the orbitofrontal cortex. However, reversal learning is often studied in animals that have limited experience with reversals. As such, the animals are learning that reversals occur during data collection. We have examined a task regime in which monkeys have extensive experience with reversals and stable behavioral performance on a probabilistic two-arm bandit reversal learning task. We developed a Bayesian analysis approach to examine the effects of manipulations of dopamine on reversal performance in this regime. We find that the analysis can clarify the strategy of the animal. Specifically, at reversal, the monkeys switch quickly from choosing one stimulus to choosing the other, as opposed to gradually transitioning, which might be expected if they were using a naive reinforcement learning (RL) update of value. Furthermore, we found that administration of haloperidol affects the way the animals integrate prior knowledge into their choice behavior. Animals had a stronger prior on where reversals would occur on haloperidol than on levodopa (L-DOPA) or placebo. This strong prior was appropriate, because the animals had extensive experience with reversals occurring in the middle of the block. Overall, we find that Bayesian dissection of the behavior clarifies the strategy of the animals and reveals an effect of haloperidol on integration of prior information with evidence in favor of a choice reversal.
C1 [Costa, Vincent D.; Tran, Valery L.; Turchi, Janita; Averbeck, Bruno B.] NIMH, Neuropsychol Lab, NIH, Bethesda, MD 20892 USA.
RP Averbeck, BB (reprint author), NIMH, Neuropsychol Lab, NIH, Bldg 49,Room1B80,49 Convent Dr,MSC 4415, Bethesda, MD 20892 USA.
EM bruno.averbeck@nih.gov
OI Costa, Vincent/0000-0002-5412-8945
FU National Institute of Mental Health
FX This work was supported by the Intramural Research Program of the
National Institute of Mental Health.
NR 31
TC 12
Z9 12
U1 2
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 FEB 11
PY 2015
VL 35
IS 6
BP 2407
EP 2416
DI 10.1523/JNEUROSCI.1989-14.2015
PG 10
WC Neurosciences
SC Neurosciences & Neurology
GA CB5RZ
UT WOS:000349686500009
PM 25673835
ER
PT J
AU Astarita, G
Avanesian, A
Grimaldi, B
Realini, N
Justinova, Z
Panlilio, LV
Basit, A
Goldberg, SR
Piomelli, D
AF Astarita, Giuseppe
Avanesian, Agnesa
Grimaldi, Benedetto
Realini, Natalia
Justinova, Zuzana
Panlilio, Leight V.
Basit, Abdul
Goldberg, Steven R.
Piomelli, Daniele
TI Methamphetamine Accelerates Cellular Senescence through Stimulation of
De Novo Ceramide Biosynthesis
SO PLOS ONE
LA English
DT Article
ID KAPPA-B; SPHINGOLIPID METABOLISM; BETA-GALACTOSIDASE; ENDOTHELIAL-CELLS;
MASS-SPECTROMETRY; MOUSE-BRAIN; DNA-BINDING; TNF-ALPHA; RAT; APOPTOSIS
AB Methamphetamine is a highly addictive psychostimulant that causes profound damage to the brain and other body organs. Post mortem studies of human tissues have linked the use of this drug to diseases associated with aging, such as coronary atherosclerosis and pulmonary fibrosis, but the molecular mechanism underlying these findings remains unknown. Here we used functional lipidomics and transcriptomics experiments to study abnormalities in lipid metabolism in select regions of the brain and, to a greater extent, peripheral organs and tissues of rats that self-administered methamphetamine. Experiments in various cellular models (primary mouse fibroblasts and myotubes) allowed us to investigate the molecular mechanisms of systemic inflammation and cellular aging related to methamphetamine abuse. We report now that methamphetamine accelerates cellular senescence and activates transcription of genes involved in cell-cycle control and inflammation by stimulating production of the sphingolipid messenger ceramide. This pathogenic cascade is triggered by reactive oxygen species, likely generated through methamphetamine metabolism via cytochrome P-450, and involves the recruitment of nuclear factor-kappa B (NF-kappa B) to induce expression of enzymes in the de novo pathway of ceramide biosynthesis. Inhibitors of NF-kappa B signaling and ceramide formation prevent methamphetamine-induced senescence and systemic inflammation in rats self-administering the drug, attenuating their health deterioration. The results suggest new therapeutic strategies to reduce the adverse consequences of methamphetamine abuse and improve effectiveness of abstinence treatments.
C1 [Astarita, Giuseppe; Avanesian, Agnesa] Univ Calif Irvine, Dept Pharmacol, Irvine, CA 92717 USA.
[Grimaldi, Benedetto; Realini, Natalia; Basit, Abdul; Piomelli, Daniele] Italian Inst Technol, Genoa, Italy.
[Justinova, Zuzana; Panlilio, Leight V.; Goldberg, Steven R.] NIDA, Preclin Pharmacol Sect, Behav Neurosci Res Branch, Baltimore, MD USA.
[Justinova, Zuzana] Univ Maryland, Sch Med, MPRC, Dept Psychiat, Baltimore, MD 21201 USA.
[Piomelli, Daniele] Univ Calif Irvine, Dept Anat & Neurobiol, Irvine, CA 92717 USA.
RP Piomelli, D (reprint author), Italian Inst Technol, Genoa, Italy.
EM piomelli@uci.edu
RI Justinova, Zuzana/A-9109-2011;
OI Justinova, Zuzana/0000-0001-5793-7484; Basit, Abdul/0000-0002-1164-5520;
Grimaldi, Benedetto/0000-0002-2589-9302
FU National Institute on Drug Abuse [RC2 DA028902]; National Institute on
Drug Abuse, NIH, DHHS
FX These studies were funded by the National Institute on Drug Abuse (RC2
DA028902 to D. P.) and by the Intramural Research Program of the
National Institute on Drug Abuse, NIH, DHHS. The funders had no role in
study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 52
TC 3
Z9 4
U1 4
U2 11
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 FEB 11
PY 2015
VL 10
IS 2
AR e0116961
DI 10.1371/journal.pone.0116961
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CB3RF
UT WOS:000349545300028
PM 25671639
ER
PT J
AU Roychoudhuri, R
Lefebvre, F
Honda, M
Pan, L
Ji, Y
Klebanoff, CA
Nichols, CN
Fourati, S
Hegazy, AN
Goulet, JP
Gattinoni, L
Nabel, GJ
Gilliet, M
Cameron, M
Restifo, NP
Sekaly, RP
Flatz, L
AF Roychoudhuri, Rahul
Lefebvre, Francois
Honda, Mitsuo
Pan, Li
Ji, Yun
Klebanoff, Christopher A.
Nichols, Carmen N.
Fourati, Slim
Hegazy, Ahmed N.
Goulet, Jean-Philippe
Gattinoni, Luca
Nabel, Gary J.
Gilliet, Michel
Cameron, Mark
Restifo, Nicholas P.
Sekaly, Rafick P.
Flatz, Lukas
TI Transcriptional profiles reveal a stepwise developmental program of
memory CD8(+) T cell differentiation
SO VACCINE
LA English
DT Article
DE CD8; Memory T cells; T cell memory; Prime-boost vaccination; LCMV
vector; Adenovirus vector
ID INTERLEUKIN-7 RECEPTOR; EFFECTOR; EXPRESSION; VACCINE; GENERATION;
SUBSETS; LYMPHOCYTES; ANTIGEN; FATES; BET
AB The generation of CD8(+) T-cell memory is a major aim of vaccination. While distinct subsets of CD8(+) T-cells are generated following immunization that differ in their ability to confer long-term immunity against infection, the transcriptional profiles of these subsets within endogenous vaccine-induced CD8(+) T cell responses have not been resolved. Here, we measure global transcriptional profiles of endogenous effector (T-EFF), effector memory (T-EM) and central memory (T-CM) CD8(+) T-cells arising from immunization with three distinct prime-boost vaccine regimens. While a proportion of transcripts were uniquely regulated within distinct CD8(+) T cell populations, we observed progressive up- or down-regulation in the expression of a majority of differentially expressed transcripts when subsets were compared in the order T-N > T-CM > T-EM > T-EFF Strikingly, when we compared global differences in gene expression between T-N, T-CM, T-EM and T-EFF cells with known transcriptional changes that result when CD8(+) T cells repetitively encounter antigen, our analysis overwhelmingly favored a model whereby cumulative antigen stimulation drives differentiation specifically from T-N > T-CM > T-EM > T-EFF and this was common to all vaccines tested. These findings provide insight into the molecular basis of immunological memory and identify potential biomarkers for characterization of vaccine-induced responses and prediction of vaccine efficacy. (C) 2014 Elsevier Ltd. All rights reserved.
C1 [Roychoudhuri, Rahul; Honda, Mitsuo; Nabel, Gary J.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Lefebvre, Francois; Pan, Li; Nichols, Carmen N.; Fourati, Slim; Goulet, Jean-Philippe; Cameron, Mark; Sekaly, Rafick P.] Vaccine & Gene Therapy Inst, Port St Lucie, FL 34987 USA.
[Ji, Yun; Klebanoff, Christopher A.; Gattinoni, Luca; Restifo, Nicholas P.] NCI, Natl Inst Bethesda, Bethesda, MD 20892 USA.
[Hegazy, Ahmed N.] Univ Oxford, Nuffield Dept Clin Med, Translat Gastroenterol Unit, Oxford, England.
[Gilliet, Michel; Flatz, Lukas] Univ Hosp CHUV, Dept Dermatol, CH-1011 Lausanne, Switzerland.
[Flatz, Lukas] Kantonsspital, Inst Immunobiol, St Gallen, Switzerland.
RP Flatz, L (reprint author), Inst Immunobiol, Rorschacher Str 95, CH-9007 St Gallen, Switzerland.
EM roychoudhuri@mail.nih.gov; rpsekaly@vgtifl.org; lukas.flatz@gmail.com
RI Gattinoni, Luca/A-2281-2008; Ji, Yun/B-7245-2009; Roychoudhuri,
Rahul/A-7442-2010;
OI Gattinoni, Luca/0000-0003-2239-3282; Ji, Yun/0000-0001-6340-7009;
Roychoudhuri, Rahul/0000-0002-5392-1853; Fourati,
Slim/0000-0001-6609-7587; Restifo, Nicholas P./0000-0003-4229-4580
FU Intramural Research Programs of the US National Institutes of Health;
National Institute of Allergy and Infectious Diseases; National Cancer
Institute; Stiftung Propter Homines; Vaduz; Principality of
Liechtenstein; Fondation Leenaards; Medic Foundatio; European Molecular
Biology Organization (EMBO) long-term fellowship [ALTF 116-2012]; Marie
Curie fellowship [FP7-PEOPLE-2012-IEF, 330621]; Wellcome Trust
FX We thank S. Perfetto, E. Lugli, M. Vernez, A. Bergthaler and G. Fabozzi,
D.C. Macallan and G.E. Griffin for helpful insights and discussion. We
also thank R. Nguyen and D. Ambrozak for their expertise with FACS
sorting. This research was supported by the Intramural Research Programs
of the US National Institutes of Health, National Institute of Allergy
and Infectious Diseases and National Cancer Institute. L.F. is supported
by the Stiftung Propter Homines, Vaduz, Principality of Liechtenstein,
the Fondation Leenaards and the Medic Foundation. A.N.H. was supported
by a European Molecular Biology Organization (EMBO) long-term fellowship
(ALTF 116-2012) and a Marie Curie fellowship (FP7-PEOPLE-2012-IEF,
Proposal 330621). R.R. is supported by a Fellowship from the Wellcome
Trust.
NR 41
TC 9
Z9 9
U1 1
U2 3
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 FEB 11
PY 2015
VL 33
IS 7
BP 914
EP 923
DI 10.1016/j.vaccine.2014.10.007
PG 10
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA CB3AU
UT WOS:000349500900012
PM 25446821
ER
PT J
AU Zhou, CK
Pfeiffer, RM
Cleary, SD
Hoffman, HJ
Levine, PH
Chu, LW
Hsing, AW
Cook, MB
AF Zhou, Cindy Ke
Pfeiffer, Ruth M.
Cleary, Sean D.
Hoffman, Heather J.
Levine, Paul H.
Chu, Lisa W.
Hsing, Ann W.
Cook, Michael B.
TI Relationship Between Male Pattern Baldness and the Risk of Aggressive
Prostate Cancer: An Analysis of the Prostate, Lung, Colorectal, and
Ovarian Cancer Screening Trial
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; ENDOGENOUS SEX-HORMONES; ANDROGEN RECEPTOR
GENE; MALE BALDING PATTERNS; EARLY-ONSET BALDNESS; GROWTH-FACTOR AXIS;
INSULIN-RESISTANCE; ALOPECIA; HAIR; MEN
AB Purpose Male pattern baldness and prostate cancer appear to share common pathophysiologic mechanisms. However, results from previous studies that assess their relationship have been inconsistent. Therefore, we investigated the association of male pattern baldness at age 45 years with risks of overall and subtypes of prostate cancer in a large, prospective cohortthe Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial.
Methods We included 39,070 men from the usual care and screening arms of the trial cohort who had no cancer diagnosis (excluding nonmelanoma skin cancer) at the start of follow-up and recalled their hair-loss patterns at age 45 years. Hazard ratios (HRs) and 95% CIs were estimated by using Cox proportional hazards regression models with age as the time metric.
Results During follow-up (median, 2.78 years), 1,138 incident prostate cancer cases were diagnosed, 571 of which were aggressive (biopsy Gleason score 7, and/or clinical stage III or greater, and/or fatal). Compared with no baldness, frontal plus moderate vertex baldness at age 45 years was not significantly associated with overall (HR, 1.19; 95% CI, 0.98 to 1.45) or nonaggressive (HR, 0.97; 95% CI, 0.72 to 1.30) prostate cancer risk but was significantly associated with increased risk of aggressive prostate cancer (HR, 1.39; 95% CI, 1.07 to 1.80). Adjustment for covariates did not substantially alter these estimates. Other classes of baldness were not significantly associated with overall or subtypes of prostate cancer.
Conclusion Our analysis indicates that frontal plus moderate vertex baldness at age 45 years is associated with an increased risk of aggressive prostate cancer and supports the possibility of common pathophysiologic mechanisms.
C1 [Zhou, Cindy Ke; Pfeiffer, Ruth M.; Cook, Michael B.] NCI, Bethesda, MD 20892 USA.
[Zhou, Cindy Ke; Cleary, Sean D.; Hoffman, Heather J.; Levine, Paul H.] George Washington Univ, Washington, DC USA.
[Chu, Lisa W.; Hsing, Ann W.] Canc Prevent Inst Calif, Fremont, CA USA.
RP Cook, MB (reprint author), NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, 9609 Med Ctr Dr,Rm 7-E106,MSC 9774, Bethesda, MD 20892 USA.
EM cookmich@mail.nih.gov
RI Zhou, Cindy /H-2165-2015; Cook, Michael/A-5641-2009
OI Zhou, Cindy /0000-0003-4814-4305; Cook, Michael/0000-0002-0533-7302
FU Intramural Program of the Division of Cancer Epidemiology and Genetics,
National Cancer Institute, National Institutes of Health
FX Supported by the Intramural Program of the Division of Cancer
Epidemiology and Genetics, National Cancer Institute, National
Institutes of Health.
NR 68
TC 9
Z9 9
U1 2
U2 3
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 FEB 10
PY 2015
VL 33
IS 5
BP 419
EP U63
DI 10.1200/JCO.2014.55.4279
PG 11
WC Oncology
SC Oncology
GA CF3OK
UT WOS:000352458200011
PM 25225425
ER
PT J
AU Lei, J
Rudolph, A
Moysich, KB
Rafiq, S
Behrens, S
Goode, EL
Pharoah, PP
Seibold, P
Fasching, PA
Andrulis, IL
Kristensen, VN
Couch, FJ
Hamann, U
Hooning, MJ
Nevanlinna, H
Eilber, U
Bolla, MK
Dennis, J
Wang, Q
Lindblom, A
Mannermaa, A
Lambrechts, D
Garcia-Closas, M
Hall, P
Chenevix-Trench, G
Shah, M
Luben, R
Haeberle, L
Ekici, AB
Beckmann, MW
Knight, JA
Glendon, G
Tchatchou, S
Alnaes, GIG
Borresen-Dale, AL
Nord, S
Olson, JE
Hallberg, E
Vachon, C
Torres, D
Ulmer, HU
Rudiger, T
Jager, A
van Deurzen, CH
Tilanus-Linthorst, MM
Muranen, TA
Aittomaki, K
Blomqvist, C
Margolin, S
Kosma, VM
Hartikainen, JM
Kataja, V
Hatse, S
Wildiers, H
Smeets, A
Figueroa, J
Chanock, SJ
Lissowska, J
Li, J
Humphreys, K
Phillips, KA
Linn, S
Cornelissen, S
van den Broek, SAJ
Kang, D
Choi, JY
Park, SK
Yoo, KY
Hsiung, CN
Wu, PE
Hou, MF
Shen, CY
Teo, SH
Taib, NAM
Yip, CH
Ho, GF
Matsuo, K
Ito, H
Iwata, H
Tajima, K
Dunning, AM
Benitez, J
Czene, K
Sucheston, LE
Maishman, T
Tapper, WJ
Eccles, D
Easton, DF
Schmidt, MK
Chang-Claude, J
AF Lei, Jieping
Rudolph, Anja
Moysich, Kirsten B.
Rafiq, Sajjad
Behrens, Sabine
Goode, Ellen L.
Pharoah, Paul Pd
Seibold, Petra
Fasching, Peter A.
Andrulis, Irene L.
Kristensen, Vessela N.
Couch, Fergus J.
Hamann, Ute
Hooning, Maartje J.
Nevanlinna, Heli
Eilber, Ursula
Bolla, Manjeet K.
Dennis, Joe
Wang, Qin
Lindblom, Annika
Mannermaa, Arto
Lambrechts, Diether
Garcia-Closas, Montserrat
Hall, Per
Chenevix-Trench, Georgia
Shah, Mitul
Luben, Robert
Haeberle, Lothar
Ekici, Arif B.
Beckmann, Matthias W.
Knight, Julia A.
Glendon, Gord
Tchatchou, Sandrine
Alnaes, Grethe I. Grenaker
Borresen-Dale, Anne-Lise
Nord, Silje
Olson, Janet E.
Hallberg, Emily
Vachon, Celine
Torres, Diana
Ulmer, Hans-Ulrich
Ruediger, Thomas
Jager, Agnes
van Deurzen, Carolien Hm
Tilanus-Linthorst, Madeleine Ma
Muranen, Taru A.
Aittomaki, Kristiina
Blomqvist, Carl
Margolin, Sara
Kosma, Veli-Matti
Hartikainen, Jaana M.
Kataja, Vesa
Hatse, Sigrid
Wildiers, Hans
Smeets, Ann
Figueroa, Jonine
Chanock, Stephen J.
Lissowska, Jolanta
Li, Jingmei
Humphreys, Keith
Phillips, Kelly-Anne
Linn, Sabine
Cornelissen, Sten
van den Broek, Sandra Alexandra J.
Kang, Daehee
Choi, Ji-Yeob
Park, Sue K.
Yoo, Keun-Young
Hsiung, Chia-Ni
Wu, Pei-Ei
Hou, Ming-Feng
Shen, Chen-Yang
Teo, Soo Hwang
Taib, Nur Aishah Mohd
Yip, Cheng Har
Ho, Gwo Fuang
Matsuo, Keitaro
Ito, Hidemi
Iwata, Hiroji
Tajima, Kazuo
Dunning, Alison M.
Benitez, Javier
Czene, Kamila
Sucheston, Lara E.
Maishman, Tom
Tapper, William J.
Eccles, Diana
Easton, Douglas F.
Schmidt, Marjanka K.
Chang-Claude, Jenny
CA KConFab Invest
TI Assessment of variation in immunosuppressive pathway genes reveals
TGFBR2 to be associated with prognosis of estrogen receptor-negative
breast cancer after chemotherapy
SO BREAST CANCER RESEARCH
LA English
DT Article
ID REGULATORY T-CELLS; GENOME-WIDE ASSOCIATION; TUMOR-INFILTRATING
LYMPHOCYTES; ANTITUMOR IMMUNITY; SUPPRESSOR-CELLS; PREDICT RESPONSE;
PROGRESSION; ADJUVANT; OUTCOMES; SYSTEM
AB Introduction: Tumor lymphocyte infiltration is associated with clinical response to chemotherapy in estrogen receptor (ER) negative breast cancer. To identify variants in immunosuppressive pathway genes associated with prognosis after adjuvant chemotherapy for ER-negative patients, we studied stage I-III invasive breast cancer patients of European ancestry, including 9,334 ER-positive (3,151 treated with chemotherapy) and 2,334 ER-negative patients (1,499 treated with chemotherapy).
Methods: We pooled data from sixteen studies from the Breast Cancer Association Consortium (BCAC), and employed two independent studies for replications. Overall 3,610 single nucleotide polymorphisms (SNPs) in 133 genes were genotyped as part of the Collaborative Oncological Gene-environment Study, in which phenotype and clinical data were collected and harmonized. Multivariable Cox proportional hazard regression was used to assess genetic associations with overall survival (OS) and breast cancer-specific survival (BCSS). Heterogeneity according to chemotherapy or ER status was evaluated with the log-likelihood ratio test.
Results: Three independent SNPs in TGFBR2 and IL12B were associated with OS (P < 10(-3)) solely in ER-negative patients after chemotherapy (267 events). Poorer OS associated with TGFBR2 rs1367610 (G > C) (per allele hazard ratio (HR) 1.54 (95% confidence interval (CI) 1.22 to 1.95), P = 3.08 x 10(-4)) was not found in ER-negative patients without chemotherapy or ER-positive patients with chemotherapy (P for interaction < 10-3). Two SNPs in IL12B (r(2) = 0.20) showed different associations with ER-negative disease after chemotherapy: rs2546892 (G > A) with poorer OS (HR 1.50 (95% CI 1.21 to 1.86), P = 1.81 x 10(-4)), and rs2853694 (A > C) with improved OS (HR 0.73 (95% CI 0.61 to 0.87), P = 3.67 x 10(-4)). Similar associations were observed with BCSS. Association with TGFBR2 rs1367610 but not IL12B variants replicated using BCAC Asian samples and the independent Prospective Study of Outcomes in Sporadic versus Hereditary Breast Cancer Study and yielded a combined HR of 1.57 ((95% CI 1.28 to 1.94), P = 2.05 x 10(-5)) without study heterogeneity.
Conclusions: TGFBR2 variants may have prognostic and predictive value in ER-negative breast cancer patients treated with adjuvant chemotherapy. Our findings provide further insights into the development of immunotherapeutic targets for ER-negative breast cancer.
C1 [Lei, Jieping; Rudolph, Anja; Behrens, Sabine; Seibold, Petra; Eilber, Ursula; Chang-Claude, Jenny] German Canc Res Ctr, Div Canc Epidemiol, D-69120 Heidelberg, Germany.
[Moysich, Kirsten B.; Sucheston, Lara E.] Roswell Pk Canc Inst, Dept Canc Prevent & Control, Buffalo, NY 14263 USA.
[Rafiq, Sajjad; Maishman, Tom; Tapper, William J.; Eccles, Diana] Univ Southampton, Southampton Univ Hosp, Fac Med, Southampton SO16 6YD, Hants, England.
[Goode, Ellen L.; Olson, Janet E.; Hallberg, Emily; Vachon, Celine] Mayo Clin, Dept Hlth Sci Res, Rochester, MN 55905 USA.
[Pharoah, Paul Pd; Bolla, Manjeet K.; Dennis, Joe; Wang, Qin; Luben, Robert; Easton, Douglas F.] Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge CB1 8RN, England.
[Pharoah, Paul Pd; Shah, Mitul; Easton, Douglas F.] Univ Cambridge, Dept Oncol, Ctr Canc Genet Epidemiol, Cambridge CB1 8RN, England.
[Fasching, Peter A.; Haeberle, Lothar; Beckmann, Matthias W.] Univ Erlangen Nurnberg, Univ Hosp Erlangen, Dept Gynecol & Obstet, Univ Breast Ctr Franconia, D-91054 Erlangen, Germany.
[Fasching, Peter A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Hematol & Oncol, Los Angeles, CA 90095 USA.
[Andrulis, Irene L.; Glendon, Gord] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Ontario Canc Genet Network, Toronto, ON M5G 1X5, Canada.
[Andrulis, Irene L.] Univ Toronto, Kings Coll Circle 1, Dept Mol Genet, Toronto, ON M5S 1A8, Canada.
[Kristensen, Vessela N.; Alnaes, Grethe I. Grenaker; Borresen-Dale, Anne-Lise; Nord, Silje] Oslo Univ Hosp, Dept Genet, Inst Canc Res, Radiumhosp, N-0310 Oslo, Norway.
[Kristensen, Vessela N.; Alnaes, Grethe I. Grenaker; Borresen-Dale, Anne-Lise; Nord, Silje] Univ Oslo, Fac Med, Inst Clin Med, KG Jebsen Ctr Breast Canc Res, N-0450 Oslo, Norway.
[Kristensen, Vessela N.] Akershus Univ Hosp, Div Med, Dept Clin Mol Biol EpiGen, N-1478 Lorenskog, Norway.
[Couch, Fergus J.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN 55905 USA.
[Hamann, Ute; Torres, Diana] German Canc Res Ctr, Div Mol Genet Breast Canc, D-69120 Heidelberg, Germany.
[Hooning, Maartje J.; Jager, Agnes] Erasmus MC Canc Inst, Dept Med Oncol, NL-3075 EA Rotterdam, Netherlands.
[Nevanlinna, Heli; Muranen, Taru A.] Univ Helsinki, Dept Obstet & Gynecol, FI-00029 Helsinki, Finland.
[Nevanlinna, Heli; Muranen, Taru A.; Aittomaki, Kristiina; Blomqvist, Carl] Univ Helsinki, Cent Hosp, FI-00029 Helsinki, Finland.
[Lindblom, Annika] Karolinska Inst, Dept Mol Med & Surg, SE-17177 Stockholm, Sweden.
[Mannermaa, Arto; Kosma, Veli-Matti; Hartikainen, Jaana M.; Kataja, Vesa] Univ Eastern Finland, Sch Med, Inst Clin Med, Oncol, FI-70211 Kuopio, Finland.
[Mannermaa, Arto; Kosma, Veli-Matti; Hartikainen, Jaana M.] Univ Eastern Finland, Canc Ctr Eastern Finland, Bioctr Kuopio, FI-70211 Kuopio, Finland.
[Mannermaa, Arto; Kosma, Veli-Matti; Hartikainen, Jaana M.; Kataja, Vesa] Kuopio Univ Hosp, Ctr Canc, SF-70210 Kuopio, Finland.
[Lambrechts, Diether] VRC, VIB, B-3000 Leuven, Belgium.
[Lambrechts, Diether; Hatse, Sigrid] Univ Leuven, Dept Oncol, Lab Translat Genet, B-3000 Leuven, Belgium.
[Garcia-Closas, Montserrat; Figueroa, Jonine; Chanock, Stephen J.] Natl Canc Inst, Div Canc Epidemiol & Genet, Rockville, MD 20850 USA.
[Garcia-Closas, Montserrat] Inst Canc Res, Div Genet & Epidemiol, Sutton SM2 5NG, Surrey, England.
[Garcia-Closas, Montserrat] Breakthrough Breast Canc Res Ctr, Div Breast Canc Res, Inst Canc Res, London SW3 6JB, England.
[Hall, Per; Li, Jingmei; Humphreys, Keith] Karolinska Inst, Dept Med Epidemiol & Biostat, S-17177 Stockholm, Sweden.
[Chenevix-Trench, Georgia] QIMR Berghofer Med Res Inst, Brisbane, Qld 4006, Australia.
[Ekici, Arif B.] Univ Erlangen Nurnberg, Inst Human Genet, D-91054 Erlangen, Germany.
[Knight, Julia A.] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Prosserman Ctr Hlth Res, Toronto, ON M5G 1X5, Canada.
[Knight, Julia A.] Univ Toronto, Div Epidemiol, Dalla Lana Sch Publ Hlth, Toronto, ON M5T 3M7, Canada.
[Tchatchou, Sandrine] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Toronto, ON M5G 1X5, Canada.
[Torres, Diana] Pontificia Univ Javeriana, Inst Human Genet, Bogota 11001000, Colombia.
[Goode, Ellen L.; Ulmer, Hans-Ulrich] Frauenklinik Stadtklinik Baden Baden, D-7570 Baden Baden, Germany.
[Ruediger, Thomas] Stadt Klinikum Karlsruhe, Inst Pathol, D-76133 Karlsruhe, Germany.
[van Deurzen, Carolien Hm] Erasmus Univ, Med Ctr, Dept Pathol, NL-3075 EA Rotterdam, Netherlands.
[Tilanus-Linthorst, Madeleine Ma] Erasmus MC Canc Inst, Dept Surg Oncol, NL-3075 EA Rotterdam, Netherlands.
[Aittomaki, Kristiina] Univ Helsinki, Dept Clin Genet, FI-00029 Helsinki, Finland.
[Blomqvist, Carl] Univ Helsinki, Dept Oncol, FI-00029 Hus Helsinki, Finland.
[Margolin, Sara] Karolinska Inst, Dept Oncol Pathol, S-17177 Stockholm, Sweden.
[Kataja, Vesa] Jyvaskyla Cent Hosp, Jyvaskyla 40620, Finland.
[Hatse, Sigrid; Wildiers, Hans; Smeets, Ann] Univ Hosp Leuven, Multidisciplinary Breast Ctr, B-3000 Leuven, Belgium.
[Lissowska, Jolanta] Ctr Canc, Dept Canc Epidemiol & Prevent, PL-02781 Warsaw, Poland.
[Lissowska, Jolanta] M Sklodowska Curie Inst Oncol, PL-02781 Warsaw, Poland.
[Li, Jingmei] Genome Inst Singapore, Human Genet, Singapore 138672, Singapore.
[Li, Jingmei] Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore 117597, Singapore.
[Phillips, Kelly-Anne] Univ Melbourne, Ctr Epidemiol & Biostat, Melbourne Sch Populat & Global Hlth, Melbourne, Vic 3010, Australia.
[Phillips, Kelly-Anne] Univ Melbourne, Peter MacCallum Dept Oncol, Melbourne, Vic 3002, Australia.
[Linn, Sabine; Cornelissen, Sten; van den Broek, Sandra Alexandra J.; Schmidt, Marjanka K.] Netherlands Canc Inst, Div Mol Pathol, NL-1006 BE Amsterdam, Netherlands.
[Kang, Daehee; Park, Sue K.] Seoul Natl Univ, Coll Med, Dept Prevent Med, Seoul 110799, South Korea.
[Kang, Daehee; Choi, Ji-Yeob; Park, Sue K.] Seoul Natl Univ, Grad Sch, Dept Biomed Sci, Seoul 151742, South Korea.
[Yoo, Keun-Young] Seoul Natl Univ, Coll Med, Seoul 110799, South Korea.
[Hsiung, Chia-Ni; Wu, Pei-Ei; Shen, Chen-Yang] Acad Sinica, Inst Biomed Sci, Taipei 115, Taiwan.
[Wu, Pei-Ei; Shen, Chen-Yang] Acad Sinica, Taiwan Biobank, Taipei 115, Taiwan.
[Hou, Ming-Feng] Kaohsiung Med Univ, Chung Ho Mem Hosp, Dept Surg, Kaohsiung 807, Taiwan.
[Shen, Chen-Yang] China Med Univ, Coll Publ Hlth, Taichung 40402, Taiwan.
[Teo, Soo Hwang] Sime Darby Med Ctr, Canc Res Initiat Fdn, Subang Jaya 47500, Selangor, Malaysia.
[Teo, Soo Hwang; Taib, Nur Aishah Mohd; Yip, Cheng Har] Univ Malaya, Breast Canc Res Unit, Fac Med, Canc Res Inst, Kuala Lumpur 59100, Malaysia.
[Ho, Gwo Fuang] Univ Malaya, Dept Oncol, Fac Med, Kuala Lumpur 59100, Malaysia.
[Matsuo, Keitaro] Kyushu Univ, Dept Prevent Med, Fac Med SciencesLembah Pantai, Fukuoka 8128582, Japan.
[Ito, Hidemi] Aichi Canc Ctr, Res Inst, Div Epidemiol & Prevent, Chikusa Ku, Nagoya, Aichi 4648681, Japan.
[Iwata, Hiroji] Aichi Canc Ctr Hosp, Dept Breast Oncol, Chikusa Ku, Nagoya, Aichi 4648681, Japan.
[Tajima, Kazuo] Mie Univ Hosp, Epidemiol Ctr Dis Control & Prevent, Tsu, Mie 5148507, Japan.
[Benitez, Javier] Spanish Natl Canc Res Ctr CNIO, Human Genotyping Unit, Ctr Nacl Genotipado CEGEN, Human Canc Genet Programme, Madrid 28029, Spain.
[Benitez, Javier] Ctr Invest Red Enfermedades Raras CIBERER, Valencia 46010, Spain.
[Schmidt, Marjanka K.] Netherlands Canc Inst, Div Psychosocial Res & Epidemiol, NL-1006 BE Amsterdam, Netherlands.
RP Chang-Claude, J (reprint author), German Canc Res Ctr, Div Canc Epidemiol, Neuenheimer Feld 581, D-69120 Heidelberg, Germany.
EM j.chang-claude@dkfz-heidelberg.de
RI U-ID, Kyushu/C-5291-2016; Andrulis, Irene/E-7267-2013; HO, GWO
FUANG/B-8634-2010; Nord, Silje/R-5212-2016; Hartikainen,
Jaana/E-6256-2015; Li, Jingmei/I-2904-2012; Garcia-Closas, Montserrat
/F-3871-2015; Knight, Julia/A-6843-2012; Yip, Cheng-Har/B-1909-2010;
Teo, Soo-hwang/H-2353-2014
OI Dunning, Alison Margaret/0000-0001-6651-7166; Muranen,
Taru/0000-0002-5895-1808; Matsuo, Keitaro/0000-0003-1761-6314; Nord,
Silje/0000-0002-3271-5356; Rafiq, Sajjad/0000-0003-4873-4540; Phillips,
Kelly-Anne/0000-0002-0475-1771; Luben, Robert/0000-0002-5088-6343; Li,
Jingmei/0000-0001-8587-7511; Garcia-Closas, Montserrat
/0000-0003-1033-2650;
FU European Community's Seventh Framework Programme [223175,
HEALTH-F2-2009-223175]; Cancer Research UK [C1287/A10118, C1287/A10710,
C12292/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); Komen
Foundation; Breast Cancer Research Foundation; Ovarian Cancer Research
Fund; CR-UK [C1287/A10118, C1287/A12014]; European Union [BM0606]; Dutch
Cancer Society [NKI 2007-3839, 4363]; BBMRI-NL; Dutch government [NWO
184.021.007]; Dutch National Genomics Initiative; ELAN-Fond of the
University Hospital of Erlangen; Helsinki University Central Hospital
Research Fund, Academy of Finland [266528]; Finnish Cancer Society, The
Nordic Cancer Union; Sigrid Juselius Foundation; KARBAC; special
Government Funding (EVO) of Kuopio University Hospital grants; Cancer
Fund of North Savo; Finnish Cancer Organizations; University of Eastern
Finland; Stichting tegen Kanker [232-2008, 196-2010]; Deutsche
Krebshilfe e.V. [70-2892-BRI, 106332, 108253, 108419]; Hamburg Cancer
Society; German Cancer Research Center; Federal Ministry of Education
and Research (BMBF) Germany [01KH0402]; NIH [CA128978, CA116167,
CA176785, CA116201]; Norwegian Research council [155218/V40,
175240/S10]; FUGE-NFR [181600/V11]; Swizz Bridge Award; National Cancer
Institute (USA) [UM1 CA164920]; Intramural Research Funds of the
National Cancer Institute, Department of Health and Human Services, USA;
Agency for Science, Technology and Research of Singapore; US National
Institute of Health (NIH); Susan G Komen Breast Cancer Foundation; UK
National Institute for Health Research Biomedical Research Centre at the
University of Cambridge; National Health and Medical Research Council
(NHMRC); Queensland Cancer Fund; Cancer Councils of New South Wales,
Victoria, Tasmania and South Australia; Cancer Foundation of Western
Australia; NHMRC; National Breast Cancer Foundation, Cancer Australia;
National Institute of Health (USA); Ministry of Education, Science,
Sports, Culture and Technology of Japan; Ministry Health, Labour and
Welfare of Japan; National Cancer Center Research and Development Fund;
Malaysian Ministry of Science, Technology and Innovation (MOSTI);
Malaysian Ministry of Higher Education [UM.C/HlR/MOHE/06]; Cancer
Research Initiatives Foundation (CARIF); Biomedical Research Council,
Singapore [BMRC08/1/35/19/550]; National medical Research Council,
Singapore [NMRC/CG/SERI/2010]; National Research Foundation of Korea -
Ministry of Education, Science and Technology [2012-0000347]; Taiwan
Biobank project of the Institute of Biomedical Sciences, Academia
Sinica, Taiwan; Funding Breast Cancer Campaign [NOV210PR62]
FX We thank all the individuals who took part in these studies and all the
researchers, clinicians, technicians, and administrative staff who have
enabled this work to be carried out. This study would not have been
possible without the contributions of the following: Kyriaki
Michailidou, (BCAC), Andrew Berchuck (OCAC), Rosalind A Eeles, Ali Amin
Al Olama, Zsofia Kote-Jarai, Sara Benlloch (PRACTICAL), Antonis
Antoniou, Lesley McGuffog and Ken Offit (CIMBA), Andrew Lee, Ed Dicks,
Graig Luccarini and the staff of the Centre for Genetic Epidemiology
Laboratory, Anna Gonzalez-Neira and the staff of the CNIO genotyping
unit, Jacques Simard and Daniel C Tessier, Francois Bacot, Daniel
Vincent, Sylvie LaBoissiSre and Frederic Robidoux and the staff of the
McGill University and Gnome Qubec Innovation Centre, Stig E. Bojesen,
Sune F Nielsen, Borge G Nordestgaard, and the staff of the Copenhagen
DNA laboratory, and Julie M Cunningham, Sharon A Windebank, Christopher
A Hilker, Jeffret Meyer and the staff of Mayo Clinic Genotyping Core
Facility. ABCS would like to thank Annegien Broeks, Emiel Rutgers, Laura
vanat Veer, Richard van Hien, Frans Hogervorst, Senno Verhoef. HEBCS
would like to thank Kirsimari Aaltonen, Karl von Smitten, Sofia Khan,
Tuomas Heikkinen and Irja Erkki KBCP thanks Eija Myohanen and Helena
Kemilainen. LMBC thanks Gilian Peuteman, Dominiek Smeets, Thomas Van
Brussel and Kathleen Corthouts. MARIE thanks Judith Heinz, Nadia Obi,
Alina Vrieling, Muhabbet Celik, Til Olchers and Stefan Nickels. NBCS
would like to thank the following clinical collaborators: Professor Per
Eystein Lonning, MD (Section of Oncology, Institute of Medicine,
University of Bergen and Department of Oncology, Haukeland University
Hospital, Bergen, Norway), Professor Emeritus Sophie D Foss, MD
(National Resource Centre for Long-term Studies after Cancer,
Rikshospitalet-Radiumhospitalet Cancer Clinic Montebello, Oslo, Norway),
Head physician Tone Ikdahl, MD (Department of Oncology, Oslo University
Hospital, Oslo, Norway), Dr Lars Ottestad, MD (Department of Genetics
and Department of Oncology, Oslo University Hospital Radiumhospitalet),
Dr Marit Muri Holmen, MD (Department of Radiology, Oslo University
Hospital Radiumhospitalet, Oslo, Norway), Dr Vilde Haakensen, MD
(Department of Genetics and Department of Oncology, Oslo University
Hospital Radiumhospitalet and Institute for Clinical Medicine, Faculty
of Medicine, University of Oslo, Oslo, Norway), Professor Bjorn Naume,
MD (Division of Cancer Medicine and Radiotherapy, Department of
Oncology, Oslo University Hospital Radiumhospitalet, Oslo, Norway),
Professor Eiliv Lund (Department of Community Medicine, Faculty of
Health Sciences, University of Tromso - The Arctic University of Norway,
Tromso, Norway), Associate Professor slaug Helland, MD (Department of
Genetics, Institute for Cancer Research and Department of Oncology, Oslo
University Hospital Radiumhospitalet, Oslo, Norway and Institute of
Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo,
Norway), Professor Inger Torhild Gram, MD (Department of Community
Medicine, Faculty of Health Sciences, University of Tromso and Norwegian
Centre for Integrated Care and Telemedicine, University Hospital of
North Norway, Tromso, Norway), Professor Emeritus Rolf Karesen, MD
(Department of Breast and Endocrine Surgery, Institute for Clinical
Medicine, Ullevaal Hospital, Oslo University Hospital and Institute of
Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo,
Norway), Dr.; Ellen Schlichting, MD (Department for Breast and Endocrine
Surgery, Oslo University Hospital Ullevaal, Oslo, Norway), Professor
Toril Sauer, MD (Department of Pathology at Akershus University
hospital, Lorenskog, Norway), Dr Olav Engebrten, MD (Institute for
Clinical Medicine, Faculty of Medicine, University of Oslo and
Department of Oncology, Oslo University Hospital, Oslo, Norway), Dr
Margit Riis, MD (Department of Surgery, Akershus University Hospital and
Department of Clinical Molecular Biology (EpiGen), Institute of Clinical
Medicine, Akershus University Hospital, University of Oslo, Lorenskog,
Norway). OFBCR thanks Teresa Selander and Nayana Weerasooriya. PBCS
thanks Louise Brinton, Neonila Szeszenia-Dabrowska, Beata Peplonska,
Witold Zatonski, Pei Chao and Michael Stagner, RBCS would like to thank
Petra Bos, Jannet Blom, Ellen Crepin, Elisabeth Huijskens, Annette
Heemskerk and the Erasmus MC Family Cancer Clinic. SASBAC would like to
thank the Swedish Medical Research Counsel. SEARCH thanks Craig
Luccarini, Caroline Baynes, Don Conroy, Anne Stafford, Sue Irvine,
Barbara Perkins, Val Rhenius. SKKDKFZS thank all study participants,
clinicians, family doctors, researchers and technicians for their
contributions and commitment to the study. kConFab/AOCS wish to thank
Heather Thorne, Eveline Niedermayr, Charmaine Smith, Sandra Picken, all
the kConFab research nurses and staff, the heads and staff of the Family
Cancer Clinics, and the kConFab Follow Up Study for their contributions
to this resource, and the many families who contribute to kConFab.
MYBRCA thanks Phuah Sze Yee, Peter Kang, Kang In Nee, Kavitta
Sivanandan, Shivaani Mariapun, Yoon Sook-Yee, Daphne Lee and Teh Yew
Ching for DNA extraction and patient recruitment. 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/A10710, C12292/A11174,
C1281/A12014, 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 BCAC is funded by
CR-UK (C1287/A10118 and C1287/A12014). Meetings of the BCAC have been
funded by the European Union COST program (BM0606). The ABCS study was
supported by the Dutch Cancer Society (grants NKI 2007-3839; 2009 4363);
BBMRI-NL, which is a Research Infrastructure financed by the Dutch
government (NWO 184.021.007); and the Dutch National Genomics
Initiative. The work of the BBCC study was partly funded by ELAN-Fond of
the University Hospital of Erlangen. The HEBCS study was financially
supported by the Helsinki University Central Hospital Research Fund,
Academy of Finland (266528), the Finnish Cancer Society, The Nordic
Cancer Union and the Sigrid Juselius Foundation. Financial support for
KARBAC study was provided through the regional agreement on medical
training and clinical research (ALF) between Stockholm County Council
and Karolinska Institute, the Swedish Cancer Society, The Gustav V
Jubilee foundation and Bert von Kantzows foundation.; The KBCP study was
financially supported by the special Government Funding (EVO) of Kuopio
University Hospital grants, Cancer Fund of North Savo, the Finnish
Cancer Organizations, and by the strategic funding of the University of
Eastern Finland. The LMBC study is supported by the Stichting tegen
Kanker (232-2008 and 196-2010). The MARIE study was supported by the
Deutsche Krebshilfe e.V. (70-2892-BRI, 106332, 108253, 108419), the
Hamburg Cancer Society, the German Cancer Research Center and the
Federal Ministry of Education and Research (BMBF) Germany (01KH0402).
The MCBCS study was supported by the NIH grants CA128978, CA116167,
CA176785 and NIH Specialized Program of Research Excellence (SPORE) in
Breast Cancer (CA116201), and 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. The NBCS study was
supported by grants from the Norwegian Research council, 155218/V40,
175240/S10 to ALBD, FUGE-NFR 181600/V11 to VNK and a Swizz Bridge Award
to ALBD. The OFBCR study was supported by grant UM1 CA164920 from the
National Cancer Institute (USA). The PBCS study was funded by Intramural
Research Funds of the National Cancer Institute, Department of Health
and Human Services, USA. The RBCS study was funded by the Dutch Cancer
Society (DDHK 2004-3124, DDHK 2009-4318). The SASBAC study 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. The SEARCH study is funded by a
program 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. The SKKDKFZS study is supported by the
German Cancer Research Center. The kConFab study is supported by a grant
from the National Breast Cancer Foundation, and previously by the
National Health and Medical Research Council (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 follow-up study has received funding from the NHMRC, the
National Breast Cancer Foundation, Cancer Australia, and the National
Institute of Health (USA). KAP is a National Breast Cancer Foundation
Fellow (Australia). The HERPACC study was supported by a Grant-in-Aid
for Scientific Research on Priority Areas from the Ministry of
Education, Science, Sports, Culture and Technology of Japan, by a
Grant-in-Aid for the Third Term Comprehensive 10-Year Strategy for
Cancer Control from Ministry Health, Labour and Welfare of Japan, by
Health and Labour Sciences Research Grants for Research on Applying
Health Technology from Ministry Health, Labour and Welfare of Japan and
by National Cancer Center Research and Development Fund. The MYBRCA
study is funded by research grants from the Malaysian Ministry of
Science, Technology and Innovation (MOSTI), Malaysian Ministry of Higher
Education (UM.C/HlR/MOHE/06) and Cancer Research Initiatives Foundation
(CARIF). Additional controls were recruited by the Singapore Eye
Research Institute, which was supported by a grant from the Biomedical
Research Council (BMRC08/1/35/19/550), Singapore and the National
medical Research Council, Singapore (NMRC/CG/SERI/2010).; The SEBCS
study was supported by the BRL (Basic Research Laboratory) program
through the National Research Foundation of Korea funded by the Ministry
of Education, Science and Technology (2012-0000347). The TWBCS study is
supported by the Taiwan Biobank project of the Institute of Biomedical
Sciences, Academia Sinica, Taiwan. The POSH study was supported by
Funding Breast Cancer Campaign (NOV210PR62) and Cancer Research UK
(C1275/A9896). 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 (BCFR),
nor does mention of trade names, commercial products, or organizations
imply endorsement by the USA Government or the BCFR. Douglas F Easton is
a Principal Research Fellow of Cancer Research UK. The funders had no
roles in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 51
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U1 0
U2 10
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1465-542X
EI 1465-5411
J9 BREAST CANCER RES
JI Breast Cancer Res.
PD FEB 10
PY 2015
VL 17
AR 18
DI 10.1186/s13058-015-0522-2
PG 13
WC Oncology
SC Oncology
GA CE7YQ
UT WOS:000352058300001
PM 25849327
ER
PT J
AU Tamrat, R
Peralta, CA
Tajuddin, SM
Evans, MK
Zonderman, AB
Crews, DC
AF Tamrat, Ruth
Peralta, Carmen A.
Tajuddin, Salman M.
Evans, Michele K.
Zonderman, Alan B.
Crews, Deidra C.
TI Apolipoprotein L1, income and early kidney damage
SO BMC NEPHROLOGY
LA English
DT Article
DE APOL1; Chronic kidney disease; Socioeconomic status; African American;
Renal; Albuminuria
ID AFRICAN-AMERICANS; APOL1 VARIANTS; SOCIOECONOMIC-STATUS;
RACIAL-DIFFERENCES; FUNCTION DECLINE; RENAL-DISEASE; UNITED-STATES;
CYSTATIN C; RISK; ASSOCIATION
AB Background: The degree to which genetic or environmental factors are associated with early kidney damage among African Americans (AAs) is unknown.
Methods: Among 462 AAs in the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study, we examined the cross-sectional association between apolipoprotein L1 (APOL1) risk variants and income with: 1) mildly reduced eGFR (<75 mL/min/1.73 m(2), creatinine-cystatin C equation) and 2) elevated urine albumin-to-creatinine ratio (ACR) (>= 17 in men and >= 25 mg/g in women). High risk APOL1 status was defined by 2 copies of high-risk variants; low risk if 0 or 1 copy. Income groups were dichotomized as < $ 14,000/year (lowest income group) or >= $ 14,000/year. Logistic regression models were adjusted for age, sex, and % European ancestry.
Results: Overall, participants' mean age was 47 years and 16% (n = 73) had high risk APOL1 status. Mean eGFR was 99 mL/min/1.73 m(2). Mildly reduced eGFR was prevalent among 11% (n = 51). The lowest income group had higher adjusted odds (aOR) of mildly reduced eGFR than the higher income group (aOR 1.8, 95% CI 1.2-2.7). High-risk APOL1 was not significantly associated with reduced eGFR (aOR 1.5, 95% CI 0.9-2.5). Among 301 participants with ACR data, 7% (n = 21) had elevated ACR. Compared to low-risk, persons with high-risk APOL1 had higher odds of elevated ACR (aOR 3.8, 95% CI 2.0-7.3). Income was not significantly associated with elevated ACR (aOR 1.8, 95% CI 0.7-4.5). There were no significant interactions between APOL1 and income.
Conclusions: Both genetic and socioeconomic factors may be important determinants of early kidney damage among AAs.
C1 [Tamrat, Ruth; Crews, Deidra C.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA.
[Peralta, Carmen A.] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA.
[Peralta, Carmen A.] San Francisco VA Med Ctr, San Francisco, CA USA.
[Tajuddin, Salman M.; Evans, Michele K.; Zonderman, Alan B.] NIA, Lab Epidemiol & Populat Sci, NIH, Baltimore, MD 21224 USA.
[Crews, Deidra C.] Johns Hopkins Med Inst, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD 21205 USA.
[Crews, Deidra C.] Johns Hopkins Med Inst, Ctr Aging & Hlth, Baltimore, MD 21205 USA.
[Crews, Deidra C.] Johns Hopkins Univ, Sch Med, Johns Hopkins Bayview Med Ctr, Div Nephrol, Baltimore, MD 21224 USA.
RP Crews, DC (reprint author), Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA.
EM dcrews1@jhmi.edu
OI Zonderman, Alan B/0000-0002-6523-4778; Tajuddin, Salman
M./0000-0002-7919-8528
FU Intramural Research Program of the National Institute on Aging, National
Institutes of Health (NIH); Robert Wood Johnson Foundation; National
Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
[K23DK097184]; Gilbert S. Omenn Anniversary Fellowship of the Institute
of Medicine
FX This work was supported by the Intramural Research Program of the
National Institute on Aging, National Institutes of Health (NIH). Dr.
Crews was supported by the Harold Amos Medical Faculty Development
Program of the Robert Wood Johnson Foundation, grant K23DK097184 from
the National Institute of Diabetes and Digestive and Kidney Diseases
(NIDDK), NIH, and the Gilbert S. Omenn Anniversary Fellowship of the
Institute of Medicine.
NR 32
TC 2
Z9 2
U1 0
U2 0
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2369
J9 BMC NEPHROL
JI BMC Nephrol.
PD FEB 10
PY 2015
VL 16
AR 14
DI 10.1186/s12882-015-0008-6
PG 8
WC Urology & Nephrology
SC Urology & Nephrology
GA CD3ET
UT WOS:000350961400001
PM 25884165
ER
PT J
AU Yao, C
Chen, BH
Joehanes, R
Otlu, B
Zhang, XL
Liu, CY
Huan, TX
Tastan, O
Cupples, LA
Meigs, JB
Fox, CS
Freedman, JE
Courchesne, P
O'Donnell, CJ
Munson, PJ
Keles, S
Levy, D
AF Yao, Chen
Chen, Brian H.
Joehanes, Roby
Otlu, Burcak
Zhang, Xiaoling
Liu, Chunyu
Huan, Tianxiao
Tastan, Oznur
Cupples, L. Adrienne
Meigs, James B.
Fox, Caroline S.
Freedman, Jane E.
Courchesne, Paul
O'Donnell, Christopher J.
Munson, Peter J.
Keles, Sunduz
Levy, Daniel
TI Integromic Analysis of Genetic Variation and Gene Expression Identifies
Networks for Cardiovascular Disease Phenotypes
SO CIRCULATION
LA English
DT Article
DE cardiovascular disease; gene expression/regulation network; genetic
variation
ID GENOME-WIDE ASSOCIATION; CORONARY-HEART-DISEASE; SMOKING-BEHAVIOR; LOCI;
VARIANTS; RISK; CYTOSCAPE; DISCOVERY; TRAITS; MODELS
AB Background-Cardiovascular disease (CVD) reflects a highly coordinated complex of traits. Although genome-wide association studies have reported numerous single nucleotide polymorphisms (SNPs) to be associated with CVD, the role of most of these variants in disease processes remains unknown.
Methods and Results-We built a CVD network using 1512 SNPs associated with 21 CVD traits in genome-wide association studies (at P <= 5x10(-8)) and cross-linked different traits by virtue of their shared SNP associations. We then explored whole blood gene expression in relation to these SNPs in 5257 participants in the Framingham Heart Study. At a false discovery rate <0.05, we identified 370 cis-expression quantitative trait loci (eQTLs; SNPs associated with altered expression of nearby genes) and 44 trans-eQTLs (SNPs associated with altered expression of remote genes). The eQTL network revealed 13 CVD-related modules. Searching for association of eQTL genes with CVD risk factors (lipids, blood pressure, fasting blood glucose, and body mass index) in the same individuals, we found examples in which the expression of eQTL genes was significantly associated with these CVD phenotypes. In addition, mediation tests suggested that a subset of SNPs previously associated with CVD phenotypes in genome-wide association studies may exert their function by altering expression of eQTL genes (eg, LDLR and PCSK7), which in turn may promote interindividual variation in phenotypes.
Conclusions-Using a network approach to analyze CVD traits, we identified complex networks of SNP-phenotype and SNP-transcript connections. Integrating the CVD network with phenotypic data, we identified biological pathways that may provide insights into potential drug targets for treatment or prevention of CVD.
C1 [Yao, Chen; Chen, Brian H.; Joehanes, Roby; Zhang, Xiaoling; Liu, Chunyu; Huan, Tianxiao; Cupples, L. Adrienne; Fox, Caroline S.; Courchesne, Paul; O'Donnell, Christopher J.; Levy, Daniel] NHLBI, Framingham Heart Study, NIH, Bethesda, MD 20892 USA.
[Yao, Chen; Chen, Brian H.; Joehanes, Roby; Zhang, Xiaoling; Liu, Chunyu; Huan, Tianxiao; Courchesne, Paul; Levy, Daniel] NHLBI, Populat Sci Branch, NIH, Bethesda, MD 20892 USA.
[Joehanes, Roby; Munson, Peter J.] NIH, Math & Stat Comp Lab, Ctr Informat Technol, Bethesda, MD 20892 USA.
[Otlu, Burcak] Middle E Tech Univ, Dept Chem Engn, TR-06531 Ankara, Turkey.
[Tastan, Oznur] Bilkent Univ, Dept Comp Engn, Ankara, Turkey.
[Cupples, L. Adrienne] Boston Univ, Dept Biostat, Sch Publ Hlth, Boston, MA USA.
[Meigs, James B.; Fox, Caroline S.] Harvard Univ, Sch Med, Boston, MA USA.
[Fox, Caroline S.] Brigham & Womens Hosp, Dept Med, Div Endocrinol Metab & Diabet, Boston, MA 02115 USA.
[Freedman, Jane E.] Univ Massachusetts, Sch Med, Dept Med, Worcester, MA USA.
[O'Donnell, Christopher J.] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
[Keles, Sunduz] Univ Wisconsin Madison, Dept Stat, Madison, WI USA.
[Keles, Sunduz] Univ Wisconsin Madison, Dept Biostat & Med Informat, Madison, WI USA.
RP Levy, D (reprint author), NHLBI, Framingham Heart Study, Populat Sci Branch, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA.
EM LevyD@nih.gov
FU National Institutes of Health [N01-HC-25195, U01 HG007019]; Division of
Intramural Research, National Heart, Lung, and Blood Institute, National
Institutes of Health; Division of Intramural Research, National Heart,
Lung, and Blood Institute; Center for Information Technology, National
Institutes of Health, Bethesda, MD; Bilim Akademisi, The Science
Academy, Turkey, under the BAGEP program; L'Oreal-UNESCO under the
UNESCO-L'Oreal National Fellowships Program for Young Women in Life
Sciences; Scientific and Technological Research Council of Turkey
(TUBITAK) [2211-C]; [K24 DK080140]
FX The FHS is funded by National Institutes of Health contract
N01-HC-25195. The laboratory work for this investigation was funded by
the Division of Intramural Research, National Heart, Lung, and Blood
Institute, National Institutes of Health. The analytical component of
this project was funded by the Division of Intramural Research, National
Heart, Lung, and Blood Institute, and the Center for Information
Technology, National Institutes of Health, Bethesda, MD, and a National
Institutes of Health grant (U01 HG007019). Dr Tastan acknowledges
support from Bilim Akademisi, The Science Academy, Turkey, under the
BAGEP program and support from L'Oreal-UNESCO under the UNESCO-L'Oreal
National Fellowships Program for Young Women in Life Sciences. B.O. is
supported by The Scientific and Technological Research Council of Turkey
(TUBITAK, 2211-C PhD Scholarship). J.B. Meigs is supported by K24
DK080140.
NR 50
TC 16
Z9 17
U1 3
U2 6
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0009-7322
EI 1524-4539
J9 CIRCULATION
JI Circulation
PD FEB 10
PY 2015
VL 131
IS 6
BP 536
EP U247
DI 10.1161/CIRCULATIONAHA.114.010696
PG 211
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA CA9EM
UT WOS:000349223600010
PM 25533967
ER
PT J
AU Datta, M
Via, LE
Kamoun, WS
Liu, C
Chen, W
Seano, G
Weiner, DM
Schimel, D
England, K
Martin, JD
Gao, X
Xu, L
Barry, CE
Jain, RK
AF Datta, Meenal
Via, Laura E.
Kamoun, Walid S.
Liu, Chong
Chen, Wei
Seano, Giorgio
Weiner, Danielle M.
Schimel, Daniel
England, Kathleen
Martin, John D.
Gao, Xing
Xu, Lei
Barry, Clifton E., III
Jain, Rakesh K.
TI Anti-vascular endothelial growth factor treatment normalizes
tuberculosis granuloma vasculature and improves small molecule delivery
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE antiangiogenesis; hypoxia; host-directed therapy; Mycobacterium
tuberculosis; rabbit model
ID ANTITUBERCULOSIS DRUGS; TUMOR VASCULATURE; SOLID TUMORS; CANCER;
DISEASES; NANOMEDICINE; CHEMOTHERAPY; ANGIOGENESIS; STRATEGIES;
INFECTION
AB Tuberculosis (TB) causes almost 2 million deaths annually, and an increasing number of patients are resistant to existing therapies. Patients who have TB require lengthy chemotherapy, possibly because of poor penetration of antibiotics into granulomas where the bacilli reside. Granulomas are morphologically similar to solid cancerous tumors in that they contain hypoxic microenvironments and can be highly fibrotic. Here, we show that TB-infected rabbits have impaired small molecule distribution into these disease sites due to a functionally abnormal vasculature, with a low-molecular-weight tracer accumulating only in peripheral regions of granulomatous lesions. Granuloma-associated vessels are morphologically and spatially heterogeneous, with poor vessel pericyte coverage in both human and experimental rabbit TB granulomas. Moreover, we found enhanced VEGF expression in both species. In tumors, antiangiogenic, specifically anti-VEGF, treatments can "normalize" their vasculature, reducing hypoxia and creating a window of opportunity for concurrent chemotherapy; thus, we investigated vessel normalization in rabbit TB granulomas. Treatment of TB-infected rabbits with the anti-VEGF antibody bevacizumab significantly decreased the total number of vessels while normalizing those vessels that remained. As a result, hypoxic fractions of these granulomas were reduced and small molecule tracer delivery was increased. These findings demonstrate that bevacizumab treatment promotes vascular normalization, improves small molecule delivery, and decreases hypoxia in TB granulomas, thereby providing a potential avenue to improve delivery and efficacy of current treatment regimens.
C1 [Datta, Meenal; Kamoun, Walid S.; Liu, Chong; Chen, Wei; Seano, Giorgio; Martin, John D.; Gao, Xing; Xu, Lei; Jain, Rakesh K.] Massachusetts Gen Hosp, Dept Radiat Oncol, Edwin L Steele Lab Tumor Biol, Boston, MA 02114 USA.
[Datta, Meenal; Kamoun, Walid S.; Liu, Chong; Chen, Wei; Seano, Giorgio; Martin, John D.; Gao, Xing; Xu, Lei; Jain, Rakesh K.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
[Datta, Meenal] Tufts Univ, Dept Chem & Biol Engn, Medford, MA 02155 USA.
[Via, Laura E.; Weiner, Danielle M.; Schimel, Daniel; England, Kathleen; Barry, Clifton E., III] NIAID, TB Res Sect, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
[Martin, John D.] MIT, Dept Chem Engn, Cambridge, MA 02139 USA.
[Barry, Clifton E., III] Univ Cape Town, Fac Hlth Sci, Dept Clin Lab Sci, ZA-7701 Rondebosch, South Africa.
RP Barry, CE (reprint author), NIAID, TB Res Sect, Lab Clin Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM cbarry@mail.nih.gov; jain@steele.mgh.harvard.edu
RI Barry, III, Clifton/H-3839-2012; Martin, John/L-6892-2016; Seano,
Giorgio/R-6611-2016
OI Martin, John/0000-0002-9828-8203; Seano, Giorgio/0000-0002-7294-302X
FU Bill and Melinda Gates Foundation; American Cancer Society; Children's
Tumor Foundation; Susan G. Komen Foundation [PDF14301739]; Grand
Challenges in Global Health Program; Intramural Research Program of the
NIH/National Institute of Allergy and Infectious Diseases; Korean
Ministry of Health and Welfare; [P01CA080214]
FX We thank Carolyn Smith for outstanding technical support of the
immunohistochemistry studies, and Drs. Matija Snuderl and Rehka Samuel
for their scientific input. We thank all of the participants who
enrolled in the study, as well as the staff of the International
Tuberculosis Research Center, Asan Medical Center, Pusan National
University Hospital, and the National Medical Center for their
assistance with this work. We acknowledge Seokyong Eum for his service
as a pathologist for this study. This study was supported, in part, by
Grant P01CA080214 (to R.K.J.) and by grants from the Bill and Melinda
Gates Foundation (to R.K.J.), from the American Cancer Society (to
L.X.), from the Children's Tumor Foundation (to L.X.), and from the
Susan G. Komen Foundation [Grant PDF14301739 (to G.S.)]; through the
Grand Challenges in Global Health Program to Douglas Young, Imperial
College (to C.E.B.); by the Intramural Research Program of the
NIH/National Institute of Allergy and Infectious Diseases (C.E.B.); and
by the Korean Ministry of Health and Welfare.
NR 33
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U1 3
U2 26
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 FEB 10
PY 2015
VL 112
IS 6
BP 1827
EP 1832
DI 10.1073/pnas.1424563112
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CA8XL
UT WOS:000349204200054
PM 25624495
ER
PT J
AU Kiss, JE
Brambilla, D
Glynn, SA
Mast, AE
Spencer, BR
Stone, M
Kleinman, SH
Cable, RG
AF Kiss, Joseph E.
Brambilla, Donald
Glynn, Simone A.
Mast, Alan E.
Spencer, Bryan R.
Stone, Mars
Kleinman, Steven H.
Cable, Ritchard G.
CA Natl Heart Lung Blood Inst NHLBI
TI Oral Iron Supplementation After Blood Donation A Randomized Clinical
Trial
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Article
ID STATUS EVALUATION RISE; RESTLESS LEGS SYNDROME; SERUM FERRITIN; LOW
HEMOGLOBIN; DONORS; DEFICIENCY; WOMEN; RECOVERY; STORES; PICA
AB IMPORTANCE Although blood donation is allowed every 8 weeks in the United States, recovery of hemoglobin to the currently accepted standard (12.5 g/dL) is frequently delayed, and some donors become anemic.
OBJECTIVE To determine the effect of oral iron supplementation on hemoglobin recovery time (days to recovery of 80% of hemoglobin removed) and recovery of iron stores in iron-depleted ("low ferritin," <= 26 ng/mL) and iron-replete ("higher ferritin," >26 ng/mL) blood donors.
DESIGN, SETTING, AND PARTICIPANTS Randomized, nonblinded clinical trial of blood donors stratified by ferritin level, sex, and age conducted in 4 regional blood centers in the United States in 2012. Included were 215 eligible participants aged 18 to 79 years who had not donated whole blood or red blood cells within 4 months.
INTERVENTIONS One tablet of ferrous gluconate (37.5mg of elemental iron) daily or no iron for 24 weeks (168 days) after donating a unit of whole blood (500 mL).
MAIN OUTCOMES AND MEASURES Time to recovery of 80% of the postdonation decrease in hemoglobin and recovery of ferritin level to baseline as a measure of iron stores.
RESULTS The mean baseline hemoglobin levels were comparable in the iron and no-iron groups and declined from a mean (SD) of 13.4 (1.1) g/dL to 12.0 (1.2) g/dL after donation in the low-ferritin group and from 14.2 (1.1) g/dL to 12.9 (1.2) g/dL in the higher-ferritin group. Compared with participants who did not receive iron supplementation, those who received iron supplementation had shortened time to 80% hemoglobin recovery in both the low-ferritin and higher-ferritin groups. Recovery of iron stores in all participants who received supplements took a median of 76 days (IQR, 20-126); for participants not taking iron, median recovery time was longer than 168 days (IQR, 147-> 168 days; P < .001). Without iron supplements, 67% of participants did not recover iron stores by 168 days. 168)
[GRAPHICS]
CONCLUSIONS AND RELEVANCE Among blood donors with normal hemoglobin levels, low-dose iron supplementation, compared with no supplementation, reduced time to 80% recovery of the postdonation decrease in hemoglobin concentration in donors with low ferritin (<= 26 ng/mL) or higher ferritin (>26 ng/mL). Copyright 2015 American Medical Association. All rights reserved.
C1 [Kiss, Joseph E.] Inst Transfus Med, Pittsburgh, PA 15213 USA.
[Brambilla, Donald] RTI, Rockville, MD USA.
[Glynn, Simone A.] NHLBI, Bethesda, MD 20892 USA.
[Mast, Alan E.] BloodCtr Wisconsin, Milwaukee, WI USA.
[Spencer, Bryan R.] Amer Red Cross, Dedham, MA USA.
[Stone, Mars] Blood Syst Res Inst, San Francisco, CA USA.
[Kleinman, Steven H.] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada.
[Cable, Ritchard G.] Amer Red Cross, Farmington, CT USA.
RP Kiss, JE (reprint author), Inst Transfus Med, 3636 Blvd Allies, Pittsburgh, PA 15213 USA.
EM jkiss@itxm.org
FU National Heart, Lung, and Blood Institute (NHLBI) [HHSN268201100001I,
HHSN268201100002I, HHSN268201100003I, HHSN268201100004I,
HHSN268201100005I, HHSN268201100006I]
FX This work was supported by National Heart, Lung, and Blood Institute
(NHLBI) contracts HHSN268201100001I, HHSN268201100002I,
HHSN268201100003I, HHSN268201100004I, HHSN268201100005I, and
HHSN268201100006I.
NR 24
TC 18
Z9 18
U1 0
U2 10
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 FEB 10
PY 2015
VL 313
IS 6
BP 575
EP 583
DI 10.1001/jama.2015.119
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA CA7AZ
UT WOS:000349070700017
PM 25668261
ER
PT J
AU Kieburtz, K
Tilley, BC
Elm, JJ
Babcock, D
Hauser, R
Ross, GW
Augustine, AH
Augustine, EU
Aminoff, MJ
Bodis-Wollner, IG
Boyd, J
Cambi, F
Chou, K
Christine, CW
Cines, M
Dahodwala, N
Derwent, L
Dewey, RB
Hawthorne, K
Houghton, DJ
Kamp, C
Leehey, M
Lew, MF
Liang, GSL
Luo, ST
Mari, Z
Morgan, JC
Parashos, S
Perez, A
Petrovitch, H
Rajan, S
Reichwein, S
Roth, JT
Schneider, JS
Shannon, KM
Simon, DK
Simuni, T
Singer, C
Sudarsky, L
Tanner, CM
Umeh, CC
Williams, K
Wills, AM
AF Kieburtz, Karl
Tilley, Barbara C.
Elm, Jordan J.
Babcock, Debra
Hauser, Robert
Ross, G. Webster
Augustine, Alicia H.
Augustine, Erika U.
Aminoff, Michael J.
Bodis-Wollner, Ivan G.
Boyd, James
Cambi, Franca
Chou, Kelvin
Christine, Chadwick W.
Cines, Michelle
Dahodwala, Nabila
Derwent, Lorelei
Dewey, Richard B., Jr.
Hawthorne, Katherine
Houghton, David J.
Kamp, Cornelia
Leehey, Maureen
Lew, Mark F.
Liang, Grace S. Lin
Luo, Sheng T.
Mari, Zoltan
Morgan, John C.
Parashos, Sotirios
Perez, Adriana
Petrovitch, Helen
Rajan, Suja
Reichwein, Sue
Roth, Jessie Tatsuno
Schneider, Jay S.
Shannon, Kathleen M.
Simon, David K.
Simuni, Tanya
Singer, Carlos
Sudarsky, Lewis
Tanner, Caroline M.
Umeh, Chizoba C.
Williams, Karen
Wills, Anne-Marie
CA Writing Grp NINDS Exploratory
TI Effect of Creatine Monohydrate on Clinical Progression in Patients With
Parkinson Disease A Randomized Clinical Trial
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Article
ID UNITED-STATES; QUESTIONNAIRE; MINOCYCLINE; LEVODOPA; QUALITY; TESTS
AB IMPORTANCE There are no treatments available to slow or prevent the progression of Parkinson disease, despite its global prevalence and significant health care burden. The National Institute of Neurological Disorders and Stroke Exploratory Trials in Parkinson Disease program was established to promote discovery of potential therapies.
OBJECTIVE To determine whether creatine monohydrate was more effective than placebo in slowing long-term clinical decline in participants with Parkinson disease.
DESIGN, SETTING, AND PATIENTS The Long-term Study 1, a multicenter, double-blind, parallel-group, placebo-controlled, 1: 1 randomized efficacy trial. Participants were recruited from 45 investigative sites in the United States and Canada and included 1741 men and women with early (within 5 years of diagnosis) and treated (receiving dopaminergic therapy) Parkinson disease. Participants were enrolled from March 2007 to May 2010 and followed up until September 2013.
INTERVENTIONS Participants were randomized to placebo or creatine (10 g/d) monohydrate for a minimum of 5 years (maximum follow-up, 8 years).
MAIN OUTCOMES AND MEASURES The primary outcome measure was a difference in clinical decline from baseline to 5-year follow-up, compared between the 2 treatment groups using a global statistical test. Clinical status was defined by 5 outcome measures: Modified Rankin Scale, Symbol Digit Modalities Test, PDQ-39 Summary Index, Schwab and England Activities of Daily Living scale, and ambulatory capacity. All outcomes were coded such that higher scores indicated worse outcomes and were analyzed by a global statistical test. Higher summed ranks (range, 5-4775) indicate worse outcomes.
RESULTS The trial was terminated early for futility based on results of a planned interim analysis of participants enrolled at least 5 years prior to the date of the analysis (n = 955). The median follow-up time was 4 years. Of the 955 participants, the mean of the summed ranks for placebo was 2360 (95% CI, 2249-2470) and for creatine was 2414 (95% CI, 2304-2524). The global statistical test yielded t1865.8 = -0.75 (2-sided P = .45). There were no detectable differences (P <.01 to partially adjust for multiple comparisons) in adverse and serious adverse events by body system.
CONCLUSIONS AND RELEVANCE Among patients with early and treated Parkinson disease, treatment with creatine monohydrate for at least 5 years, compared with placebo did not improve clinical outcomes. These findings do not support the use of creatine monohydrate in patients with Parkinson disease. Copyright 2015 American Medical Association. All rights reserved.
C1 [Kieburtz, Karl; Augustine, Alicia H.; Augustine, Erika U.; Kamp, Cornelia] Univ Rochester, Rochester, NY 14642 USA.
[Tilley, Barbara C.; Luo, Sheng T.; Perez, Adriana; Rajan, Suja] Univ Texas Hlth Sci Ctr Houston, Houston, TX 77030 USA.
[Elm, Jordan J.] Med Univ S Carolina, Charleston, SC USA.
[Babcock, Debra] NIH, Bethesda, MD 20892 USA.
[Hauser, Robert] Univ S Florida, Tampa, FL USA.
[Ross, G. Webster; Petrovitch, Helen] Pacific Hlth Res & Educ Inst, Honolulu, HI USA.
[Aminoff, Michael J.; Christine, Chadwick W.; Roth, Jessie Tatsuno] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Bodis-Wollner, Ivan G.] Suny Downstate Med Ctr, Brooklyn, NY 11203 USA.
[Boyd, James] Univ Vermont, Burlington, VT 05405 USA.
[Cambi, Franca] Univ Kentucky, Lexington, KY 40506 USA.
[Chou, Kelvin] Univ Michigan, Ann Arbor, MI 48109 USA.
[Cines, Michelle] Univ Maryland, Sch Med, Baltimore, MD 21201 USA.
[Dahodwala, Nabila; Reichwein, Sue] Univ Penn, Philadelphia, PA 19104 USA.
[Derwent, Lorelei] Univ Calgary, Calgary, AB, Canada.
[Dewey, Richard B., Jr.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA.
[Hawthorne, Katherine; Lew, Mark F.] Univ So Calif, Los Angeles, CA USA.
[Houghton, David J.] Ochsner Med Ctr, New Orleans, LA USA.
[Leehey, Maureen] Univ Colorado Denver, Aurora, CO USA.
[Liang, Grace S. Lin; Tanner, Caroline M.] Parkinsons Inst & Clin Ctr, Sunnyvale, CA USA.
[Mari, Zoltan] Johns Hopkins Univ, Baltimore, MD USA.
[Morgan, John C.] Georgia Regents Univ, Augusta, GA USA.
[Parashos, Sotirios] Struthers Parkinsons Ctr, Golden Valley, MN USA.
[Schneider, Jay S.] Thomas Jefferson Univ, Philadelphia, PA 19107 USA.
[Shannon, Kathleen M.] Rush Univ, Med Ctr, Chicago, IL 60612 USA.
[Simon, David K.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
[Simuni, Tanya; Williams, Karen] Northwestern Univ, Chicago, IL 60611 USA.
[Singer, Carlos] Univ Miami, Miami, FL USA.
[Sudarsky, Lewis; Umeh, Chizoba C.; Wills, Anne-Marie] Brigham & Womens Hosp, Boston, MA 02115 USA.
RP Kieburtz, K (reprint author), Univ Rochester, Ctr Human Expt Therapeut, 265 Crittenden Blvd,POB 694, Rochester, NY 14642 USA.
EM karl.kieburtz@chet.rochester.edu
FU National Institute of Neurological Disorders and Stroke (NINDS)
[U01NS43128]
FX Financial support for the LS-1 study was provided by National Institute
of Neurological Disorders and Stroke (NINDS) grant U01NS43128.
NR 31
TC 28
Z9 29
U1 3
U2 14
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 FEB 10
PY 2015
VL 313
IS 6
BP 584
EP 593
DI 10.1001/jama.2015.120
PG 10
WC Medicine, General & Internal
SC General & Internal Medicine
GA CA7AZ
UT WOS:000349070700018
ER
PT J
AU Gadalla, SM
Wang, T
Haagenson, M
Spellman, SR
Lee, SJ
Williams, KM
Wong, JY
De Vivo, I
Savage, SA
AF Gadalla, Shahinaz M.
Wang, Tao
Haagenson, Michael
Spellman, Stephen R.
Lee, Stephanie J.
Williams, Kirsten M.
Wong, Jason Y.
De Vivo, Immaculata
Savage, Sharon A.
TI Association Between Donor Leukocyte Telomere Length and Survival After
Unrelated Allogeneic Hematopoietic Cell Transplantation for Severe
Aplastic Anemia
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Article
ID BONE-MARROW-TRANSPLANTATION; VERSUS-HOST-DISEASE; RISK-FACTORS;
CHILDREN; SENESCENCE; PATHOPHYSIOLOGY; RECIPIENTS; FAILURE; PROGRAM; AGE
AB IMPORTANCE Telomeres protect chromosome ends and are markers of cellular aging and replicative capacity.
OBJECTIVE To evaluate the association between recipient and donor pretransplant leukocyte telomere length with outcomes after unrelated donor allogeneic hematopoietic cell transplantation (HCT) for patients with severe aplastic anemia.
DESIGN, PARTICIPANTS, AND SETTING The study included 330 patients (235 acquired, 85 Fanconi anemia, and 10 Diamond-Blackfan anemia) and their unrelated donors who had pre-HCT blood samples and clinical and outcome data available at the Center for International Blood and Marrow Transplant Research. Patients underwent HCT between 1989 and 2007 in 84 centers and were followed-up to March 2013.
EXPOSURES Recipient and donor pre-HCT leukocyte telomere length classified into long (third tertile) and short (first and second tertiles combined) based on donor telomere length distribution.
MAIN OUTCOMES AND MEASURES Overall survival, neutrophil recovery, and acute and chronic graft-vs-host disease, as ascertained by transplant centers through regular patient follow-up.
RESULTS Longer donor leukocyte telomere length was associated with higher survival probability (5-year overall survival, 56%; number at risk, 57; cumulative deaths, 50) than shorter donor leukocyte telomere length (5-year overall survival, 40%; number at risk, 71; cumulative deaths, 128; P = .009). The association remained statistically significant after adjusting for donor age, disease subtype, Karnofsky performance score, graft type, HLA matching, prior aplastic anemia therapy, race/ethnicity, and calendar year of transplant (hazard ratio [HR], 0.61; 95% CI, 0.44-0.86). Similar results were noted in analyses stratified on severe aplastic anemia subtype, recipient age, HLA matching, calendar year of transplant, and conditioning regimen. There was no association between donor telomere length and neutrophil engraftment at 28 days (cumulative incidence, 86% vs 85%; HR, 0.94; 95% CI, 0.73-1.22), acute graft-vs-host disease grades III-IV at 100 days (cumulative incidence, 22% vs 28%; HR, 0.77; 95% CI, 0.48-1.23), or chronic graft-vs-host disease at 1-year (cumulative incidence, 28% vs 30%; HR, 0.81; 95% CI, 0.53-1.24) for long vs short, respectively. Pretransplant leukocyte telomere length in the recipients was not associated with posttransplant survival (HR, 0.91; 95% CI, 0.64-1.30).
CONCLUSIONS AND RELEVANCE Longer donor leukocyte telomere length was associated with increased 5-year survival in patients who received HCT for severe aplastic anemia. Patient leukocyte telomere length was not associated with survival. The results of this observational study suggest that donor leukocyte telomere length may have a role in long-term posttransplant survival. Copyright 2015 American Medical Association. All rights reserved.
C1 [Gadalla, Shahinaz M.; Savage, Sharon A.] NCI, Clin Genet Branch, NIH, Rockville, MD 20850 USA.
[Wang, Tao; Lee, Stephanie J.] Med Coll Wisconsin, Ctr Int Blood & Marrow Transplant hRes, Milwaukee, WI 53226 USA.
[Wang, Tao; Lee, Stephanie J.] Med Coll Wisconsin, Div Biostat, Milwaukee, WI 53226 USA.
[Haagenson, Michael; Spellman, Stephen R.] Ctr Int Blood & Marrow Transplant Res, Minneapolis, MN USA.
[Lee, Stephanie J.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA.
[Williams, Kirsten M.] George Washington Univ, Med Ctr, Div Blood & Marrow Transplantat, Ctr Canc & Blood Disorders,Childrens Natl Med Ctr, Washington, DC 20037 USA.
[Williams, Kirsten M.] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA.
[Wong, Jason Y.; De Vivo, Immaculata] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA.
[Wong, Jason Y.; De Vivo, Immaculata] Harvard Univ, Sch Med, Boston, MA USA.
[Wong, Jason Y.; De Vivo, Immaculata] Harvard Univ, Sch Publ Hlth, Program Genet Epidemiol & Stat Genet, Boston, MA 02115 USA.
RP Gadalla, SM (reprint author), NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, NIH, 9609 Med Ctr Dr,Room 6E-534, Rockville, MD 20850 USA.
EM gadallas@mail.nih.gov
RI Savage, Sharon/B-9747-2015;
OI Savage, Sharon/0000-0001-6006-0740; Wong, Jason/0000-0002-8167-540X
FU Public Health Service from the National Cancer Institute [U24-CA76518];
National Heart, Lung, and Blood Institute; National Institute of Allergy
and Infectious Diseases, Health Resources; Services Administration
[HHSH234200637015C]; Office of Naval Research [N00014-13-1-0039,
N00014-14-1-0028]; National Institutes of Health [2R01 CA082838];
Intramural Research Program of the National Cancer Institute
FX The study was supported by Public Health Service grant U24-CA76518 from
the National Cancer Institute, the National Heart, Lung, and Blood
Institute and the National Institute of Allergy and Infectious Diseases,
Health Resources (Drs Wang and Lee and Messrs Haagenson and Spellman),
and grant HHSH234200637015C from the Services Administration, grants
N00014-13-1-0039 and N00014-14-1-0028 from the Office of Naval Research
(Dr Wang and Messrs Haagenson and Spellman), grant 2R01 CA082838 from
the National Institutes of Health (Dr De Vivo), and the Intramural
Research Program of the National Cancer Institute (Drs Gadalla and
Savage).
NR 36
TC 13
Z9 13
U1 1
U2 8
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 FEB 10
PY 2015
VL 313
IS 6
BP 594
EP 602
DI 10.1001/jama.2015.7
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA CA7AZ
UT WOS:000349070700019
PM 25668263
ER
PT J
AU Kiss, JE
Brambilla, D
Glynn, SA
Mast, AE
Spencer, BR
Stone, M
Kleinman, SH
Cable, RG
AF Kiss, Joseph E.
Brambilla, Donald
Glynn, Simone A.
Mast, Alan E.
Spencer, Bryan R.
Stone, Mars
Kleinman, Steven H.
Cable, Ritchard G.
CA Natl Heart Lung Blood Inst NHLBI
TI Oral Iron Supplementation After Blood Donation A Randomized Clinical
Trial (vol 313, pg 575, 2015)
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Correction
C1 [Kiss, Joseph E.] Inst Transfus Med, Pittsburgh, PA 15213 USA.
[Brambilla, Donald] RTI, Rockville, MD USA.
[Glynn, Simone A.] NHLBI, Bethesda, MD 20892 USA.
[Mast, Alan E.] BloodCtr Wisconsin, Milwaukee, WI USA.
[Spencer, Bryan R.] Amer Red Cross, Dedham, MA USA.
[Stone, Mars] Blood Syst Res Inst, San Francisco, CA USA.
[Kleinman, Steven H.] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada.
[Cable, Ritchard G.] Amer Red Cross, Farmington, CT USA.
RP Kiss, JE (reprint author), Inst Transfus Med, 3636 Blvd Allies, Pittsburgh, PA 15213 USA.
EM jkiss@itxm.org
NR 1
TC 0
Z9 0
U1 0
U2 1
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 FEB 10
PY 2015
VL 313
IS 6
PG 1
WC Medicine, General & Internal
SC General & Internal Medicine
GA CA7AZ
UT WOS:000349070700016
ER
PT J
AU Gabriel, EE
Sachs, MC
Gilbert, PB
AF Gabriel, Erin E.
Sachs, Michael C.
Gilbert, Peter B.
TI Comparing and combining biomarkers as principle surrogates for
time-to-event clinical endpoints
SO STATISTICS IN MEDICINE
LA English
DT Article
DE causal inference; surrogate endpoint evaluation; survival analysis;
accuracy measures; multivariate principal stratification
ID VACCINE TRIALS; MARKERS
AB Principal surrogate endpoints are useful as targets for phase I and II trials. In many recent trials, multiple post-randomization biomarkers are measured. However, few statistical methods exist for comparison of or combination of biomarkers as principal surrogates, and none of these methods to our knowledge utilize time-to-event clinical endpoint information. We propose a Weibull model extension of the semi-parametric estimated maximum likelihood method that allows for the inclusion of multiple biomarkers in the same risk model as multivariate candidate principal surrogates. We propose several methods for comparing candidate principal surrogates and evaluating multivariate principal surrogates. These include the time-dependent and surrogate-dependent true and false positive fraction, the time-dependent and the integrated standardized total gain, and the cumulative distribution function of the risk difference. We illustrate the operating characteristics of our proposed methods in simulations and outline how these statistics can be used to evaluate and compare candidate principal surrogates. We use these methods to investigate candidate surrogates in the Diabetes Control and Complications Trial. Copyright (c) 2014 John Wiley & Sons, Ltd.
C1 [Gabriel, Erin E.; Gilbert, Peter B.] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, Seattle, WA 98109 USA.
[Sachs, Michael C.] NCI, Biometr Res Branch, Washington, DC USA.
[Gilbert, Peter B.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
RP Gabriel, EE (reprint author), Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, Seattle, WA 98109 USA.
EM egabriel@fhcrc.org
OI Gabriel, Erin/0000-0002-0504-8404
FU NIAID NIH HHS [UM1 AI068635, R37 AI054165]
NR 20
TC 2
Z9 2
U1 0
U2 7
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 FEB 10
PY 2015
VL 34
IS 3
BP 381
EP 395
DI 10.1002/sim.6349
PG 15
WC Mathematical & Computational Biology; Public, Environmental &
Occupational Health; Medical Informatics; Medicine, Research &
Experimental; Statistics & Probability
SC Mathematical & Computational Biology; Public, Environmental &
Occupational Health; Medical Informatics; Research & Experimental
Medicine; Mathematics
GA AY6XC
UT WOS:000347705100002
PM 25352131
ER
PT J
AU Felix, AS
Sherman, ME
Hewitt, SM
Gunja, MZ
Yang, HP
Cora, RL
Boudreau, V
Ylaya, K
Lissowska, J
Brinton, LA
Wentzensen, N
AF Felix, Ashley S.
Sherman, Mark E.
Hewitt, Stephen M.
Gunja, Munira Z.
Yang, Hannah P.
Cora, Renata L.
Boudreau, Vicky
Ylaya, Kris
Lissowska, Jolanta
Brinton, Louise A.
Wentzensen, Nicolas
TI Cell-cycle protein expression in a population-based study of ovarian and
endometrial cancers
SO FRONTIERS IN ONCOLOGY
LA English
DT Article
DE molecular etiology; prognosis; gynecologic cancer; cell-cycle
ID REGULATORY PROTEINS; CLINICOPATHOLOGICAL PARAMETERS;
SUBCELLULAR-LOCALIZATION; PROGNOSTIC-SIGNIFICANCE; P27(KIP1) EXPRESSION;
PROMOTER METHYLATION; HUMAN-PAPILLOMAVIRUS; POOR-PROGNOSIS; INHIBITOR
P27; CARCINOMA
AB Aberrant expression of cyclin-dependent kinase (CDK) inhibitors is implicated in the carcinogenesis of many cancers, including ovarian and endometrial cancers. We examined associations between CDK inhibitor expression, cancer risk factors, tumor characteristics, and survival outcomes among ovarian and endometrial cancer patients enrolled in a population-based case-control study. Expression (negative vs. positive) of three CDK inhibitors (p16, p21, and p27) and ki67 was examined with immunohistochemical staining of tissue microarrays. Logistic regression was used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (Cis) for associations between biomarkers, risk factors, and tumor characteristics. Survival outcomes were only available for ovarian cancer patients and examined using Kaplan Meier plots and Cox proportional hazards regression. Among ovarian cancer patients (n=175), positive p21 expression was associated with endometrioid tumors (OR = 12.22, 95% Cl = 1.45-102.78) and higher overall survival (logrank p= 0.002). In Cox models adjusted for stage, grade, and histology, the association between p21 expression and overall survival was borderline significant (hazard ratio = 0.65, 95% CI = 0.42-1.05). Among endometrial cancer patients (n= 289), positive p21 expression was inversely associated with age (OR > 65 years of age= 0.25, 95% Cl = 0.07-0.84) and current smoking status (OR: 0.33, 95% Cl 0.15, 0.72) compared to negative expression. Our study showed heterogeneity in expression of cell-cycle proteins associated with risk factors and tumor characteristics of gynecologic cancers. Future studies to assess these markers of etiological classification and behavior may be warranted.
C1 [Felix, Ashley S.; Gunja, Munira Z.; Yang, Hannah P.; Cora, Renata L.; Boudreau, Vicky; Brinton, Louise A.; Wentzensen, Nicolas] NCI, Hormonaland Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Felix, Ashley S.] NCI, Canc Prevent Fellowship Program, Div Canc Prevent, NIH, Bethesda, MD 20892 USA.
[Sherman, Mark E.] NCI, Breast & Gynecol Canc Res Grp, Div Canc Prevent, NIH, Bethesda, MD 20892 USA.
[Hewitt, Stephen M.] NCI, Lab Pathol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Ylaya, Kris] NCI, Tissue Array Res Program, NIH, Bethesda, MD 20892 USA.
[Lissowska, Jolanta] Maria Sklodowska Curie Mem Canc Ctr & Inst Oncol, Warsaw, Poland.
RP Felix, AS (reprint author), NCI, Hormonaland Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, 9609 Med Ctr Dr,7E214, Bethesda, MD 20892 USA.
EM ashley.felix@nih.gov
RI Brinton, Louise/G-7486-2015;
OI Brinton, Louise/0000-0003-3853-8562; Hewitt, Stephen/0000-0001-8283-1788
FU National Cancer Institute
FX This research was supported (in part) by the Intramural Research Program
of the National Cancer Institute.
NR 46
TC 4
Z9 5
U1 1
U2 4
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015,
SWITZERLAND
SN 2234-943X
J9 FRONT ONCOL
JI Front. Oncol.
PD FEB 9
PY 2015
VL 5
AR 25
DI 10.3389/fonc.2015.00025
PG 11
WC Oncology
SC Oncology
GA CO3QS
UT WOS:000359074400001
PM 25709969
ER
PT J
AU Liu, JJ
Green, P
Mann, JJ
Rapoport, SI
Sublette, ME
AF Liu, Joanne J.
Green, Pnina
Mann, J. John
Rapoport, Stanley I.
Sublette, M. Elizabeth
TI Pathways of polyunsaturated fatty acid utilization: Implications for
brain function in neuropsychiatric health and disease
SO BRAIN RESEARCH
LA English
DT Review
DE Polyunsaturated fatty acids; Lipid metabolism; Brain; Depression;
Bipolar disorder; Schizophrenia
ID ALPHA-LINOLENIC ACID; RAT FRONTAL-CORTEX; OMEGA-3-FATTY-ACID
DOCOSAHEXAENOIC ACID; MAJOR DEPRESSIVE DISORDER; N-3 PUFA DEPRIVATION;
PROLIFERATOR-ACTIVATED RECEPTORS; DEFICIT-HYPERACTIVITY-DISORDER;
POSITRON-EMISSION-TOMOGRAPHY; CAPILLARY ENDOTHELIAL-CELLS; HUMAN
5-HT7(A) RECEPTORS
AB Essential polyunsaturated fatty acids (PUPAS) have profound effects on brain development and function. Abnormalities of PUPA status have been implicated in neuropsychiatric diseases such as major depression, bipolar disorder, schizophrenia, Alzheimer's disease, and attention deficit hyperactivity disorder. Pathophysiologic mechanisms could involve not only suboptimal PUPA intake, but also metabolic and genetic abnormalities, defective hepatic metabolism, and problems with diffusion and transport. This article provides an overview of physiologic factors regulating PUPA utilization, highlighting their relevance to neuropsychiatric disease. (C) 2014 Elsevier B.V. All rights reserved.
C1 [Liu, Joanne J.; Mann, J. John; Sublette, M. Elizabeth] New York State Psychiat Inst & Hosp, Dept Mol Imaging & Neuropathol, New York, NY 10032 USA.
[Liu, Joanne J.] New York Med Coll, Valhalla, NY 10595 USA.
[Green, Pnina] Tel Aviv Univ, Felsenstein Med Res Ctr, Lab Metab Res, Petah Tiqwa, Israel.
[Mann, J. John; Sublette, M. Elizabeth] Columbia Univ, Dept Psychiat, New York, NY USA.
[Mann, J. John] Columbia Univ, Dept Radiol, New York, NY USA.
[Rapoport, Stanley I.] NIA, Brain Physiol & Metab Sect, Neurosci Lab, NIH, Bethesda, MD 20892 USA.
RP Sublette, ME (reprint author), New York State Psychiat Inst & Hosp, 1051 Riverside Dr,Unit 42, New York, NY 10032 USA.
EM es2316@columbia.edu
RI Sublette, M/A-8391-2009
OI Sublette, M/0000-0001-7378-4262
FU Intramural Program of the National Institute on Aging; NIMH [MH079033]
FX Work by Dr. Rapoport was supported entirely by the Intramural Program of
the National Institute on Aging. Work by Dr. Sublette was supported in
part by NIMH MH079033.
NR 546
TC 19
Z9 19
U1 2
U2 22
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0006-8993
EI 1872-6240
J9 BRAIN RES
JI Brain Res.
PD FEB 9
PY 2015
VL 1597
BP 220
EP 246
DI 10.1016/j.brainres.2014.11.059
PG 27
WC Neurosciences
SC Neurosciences & Neurology
GA CD2TA
UT WOS:000350930700021
PM 25498862
ER
PT J
AU Wang, H
Yu, CJ
Gao, X
Welte, T
Muscarella, AM
Tian, L
Zhao, H
Zhao, Z
Du, SY
Tao, JN
Lee, B
Westbrook, TF
Wong, STC
Jin, X
Rosen, JM
Osborne, CK
Zhang, XHF
AF Wang, Hai
Yu, Cuijuan
Gao, Xia
Welte, Thomas
Muscarella, Aaron M.
Tian, Lin
Zhao, Hong
Zhao, Zhen
Du, Shiyu
Tao, Jianning
Lee, Brendan
Westbrook, Thomas F.
Wong, Stephen T. C.
Jin, Xin
Rosen, Jeffrey M.
Osborne, C. Kent
Zhang, Xiang H. -F.
TI The Osteogenic Niche Promotes Early-Stage Bone Colonization of
Disseminated Breast Cancer Cells
SO CANCER CELL
LA English
DT Article
ID MESENCHYMAL STEM-CELLS; GENE-EXPRESSION; EXTRACELLULAR-MATRIX; MOLECULAR
PORTRAITS; ESTROGEN-RECEPTOR; TUMOR-CELLS; METASTASIS; THERAPY; REVEALS;
GROWTH
AB Breast cancer bone micrometastases can remain asymptomatic for years before progressing into overt lesions. The biology of this process, including the microenvironnnent niche and supporting pathways, is unclear. We find that bone micrometastases predominantly reside in a niche that exhibits features of osteogenesis. Niche interactions are mediated by heterotypic adherens junctions (hAJs) involving cancer-derived E-cadherin and osteogenic N-cadherin, the disruption of which abolishes niche-conferred advantages. We elucidate that hAJ activates the mTOR pathway in cancer cells, which drives the progression from single cells to micrometastases. Human data set analyses support the roles of AJ and the mTOR pathway in bone colonization. Our study illuminates the initiation of bone colonization, and provides potential therapeutic targets to block progression toward osteolytic metastases.
C1 [Wang, Hai; Yu, Cuijuan; Gao, Xia; Welte, Thomas; Muscarella, Aaron M.; Tian, Lin; Osborne, C. Kent; Zhang, Xiang H. -F.] Baylor Coll Med, Lester & Sue Smith Breast Ctr, Houston, TX 77030 USA.
[Tian, Lin; Westbrook, Thomas F.; Wong, Stephen T. C.; Rosen, Jeffrey M.; Osborne, C. Kent; Zhang, Xiang H. -F.] Baylor Coll Med, Dan L Duncan Canc Ctr, Houston, TX 77030 USA.
[Wang, Hai; Yu, Cuijuan; Gao, Xia; Welte, Thomas; Wong, Stephen T. C.; Rosen, Jeffrey M.; Osborne, C. Kent; Zhang, Xiang H. -F.] Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA.
[Tao, Jianning; Lee, Brendan; Westbrook, Thomas F.] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA.
[Tian, Lin; Westbrook, Thomas F.] Baylor Coll Med, Verna & Marrs McLean Dept Biochem & Mol Biol, Houston, TX 77030 USA.
[Muscarella, Aaron M.] Baylor Coll Med, Integrat Mol & Biomed Sci Grad Program, Houston, TX 77030 USA.
[Zhang, Xiang H. -F.] Baylor Coll Med, McNair Med Inst, Houston, TX 77030 USA.
[Zhao, Hong; Zhao, Zhen; Wong, Stephen T. C.] Methodist Hosp, Res Inst, Weill Cornell Med Coll, NCI Ctr Modeling Canc Dev, Houston, TX 77030 USA.
[Zhao, Hong; Zhao, Zhen; Wong, Stephen T. C.] Methodist Hosp, Res Inst, Weill Cornell Med Coll, Dept Syst Med & Bioengn, Houston, TX 77030 USA.
[Zhao, Zhen] Southeast Univ, Sch Med, Dept Radiol, Nanjing 210018, Peoples R China.
[Du, Shiyu] China Japan Friendship Hosp, Dept Gastroenterol, Beijing 100029, Peoples R China.
[Wong, Stephen T. C.] Houston Methodist Hosp, Dept Radiol, Houston, TX 77459 USA.
[Jin, Xin] Eli & Edythe L Broad Inst, Canc Program, Cambridge, MA 02142 USA.
RP Zhang, XHF (reprint author), Baylor Coll Med, Lester & Sue Smith Breast Ctr, One Baylor Plaza, Houston, TX 77030 USA.
EM xiangz@bcm.edu
FU NCI [CA151293, CA183878]; Breast Cancer Research Foundation; U.S.
Department of Defense DAMD [W81XWH-13-1-0195, CA149196-04,
W81XWH-13-1-0296]; McNair Medical Institute; NIH [U54CA149196,
CA148761]; John S. Dunn Research Foundation; Ting Tsung and Wei Fong
Chao Foundation
FX We thank Dr. Max Wicha and S. Liu for generously providing us with the
immortalized human MSC cells; Dr. Robin L. Anderson for 4T1.2 cells;
Baylor Breast Center Pathology Core for technical assistance; and D.
Weiss, I.S. Kim, H.C. Lo, and Z. Duan for helpful discussions. X. H.-F.
Z. is supported by NCI CA151293, CA183878, Breast Cancer Research
Foundation, U.S. Department of Defense DAMD W81XWH-13-1-0195, a Pilot
Award of CA149196-04, and McNair Medical Institute. H.W. is supported by
U.S. Department of Defense DAMD W81XWH-13-1-0296. H. Z. and S.T.C.W. are
supported by NIH grant U54CA149196, John S. Dunn Research Foundation,
and Ting Tsung and Wei Fong Chao Foundation. Studies with the p53 null
tumors were supported by NIH grant CA148761 to J.M.R. C.K.O. is a member
on the advisory boards for Genentech, Novartis, Nanostring, AstraZeneca,
and Pfizer.
NR 49
TC 39
Z9 39
U1 4
U2 20
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 FEB 9
PY 2015
VL 27
IS 2
BP 193
EP 210
DI 10.1016/j.ccell.2014.11.017
PG 18
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA CB3GC
UT WOS:000349515200008
PM 25600338
ER
PT J
AU Walz, AL
Ooms, A
Gadd, S
Gerhard, DS
Smith, MA
Auvil, JMG
Meerzaman, D
Chen, QR
Hsu, CH
Yan, CH
Nguyen, C
Hu, Y
Bowlby, R
Brooks, D
Ma, Y
Mungall, AJ
Moore, RA
Schein, J
Marra, MA
Huff, V
Dome, JS
Chi, YY
Mullighan, CG
Ma, J
Wheeler, DA
Hampton, OA
Jafari, N
Ross, N
Gastier-Foster, JM
Perlman, EJ
AF Walz, Amy L.
Ooms, Ariadne
Gadd, Samantha
Gerhard, Daniela S.
Smith, Malcolm A.
Auvil, Jamie M. Guidry
Meerzaman, Daoud
Chen, Qing-Rong
Hsu, Chih Hao
Yan, Chunhua
Cu Nguyen
Hu, Ying
Bowlby, Reanne
Brooks, Denise
Ma, Yussanne
Mungall, Andrew J.
Moore, Richard A.
Schein, Jacqueline
Marra, Marco A.
Huff, Vicki
Dome, Jeffrey S.
Chi, Yueh-Yun
Mullighan, Charles G.
Ma, Jing
Wheeler, David A.
Hampton, Oliver A.
Jafari, Nadereh
Ross, Nicole
Gastier-Foster, Julie M.
Perlman, Elizabeth J.
TI Recurrent DGCR8, DROSHA, and SIX Homeodomain Mutations in Favorable
Histology Wilms Tumors
SO CANCER CELL
LA English
DT Article
ID DICER1 MUTATIONS; MICRORNA BIOGENESIS; SOMATIC MUTATIONS;
GENETIC-VARIATION; MAMMALIAN KIDNEY; IN-VIVO; CANCER; TUMORIGENESIS;
PHENOTYPE; ALIGNMENT
AB We report the most common single-nucleotide substitution/deletion mutations in favorable histology Wilms tumors (FHWTs) to occur within SIX1/2 (7% of 534 tumors) and microRNA processing genes (miRNAPGs) DGCR8 and DROSHA (15% of 534 tumors). Comprehensive analysis of 77 FHWTs indicates that tumors with SIX1/2 and/or miRNAPG mutations show a pre-induction metanephric mesenchyme gene expression pattern and are significantly associated with both perilobar nephrogenic rests and 11p15 imprinting aberrations. Significantly decreased expression of mature Let-7a and the miR-200 family (responsible for mesenchymal-to-epithelial transition) in miRNAPG mutant tumors is associated with an undifferentiated blastemal histology. The combination of SIX and miRNAPG mutations in the same tumor is associated with evidence of RAS activation and a higher rate of relapse and death.
C1 [Walz, Amy L.] Northwestern Univ, Feinberg Sch Med, Ann & Robert H Lurie Childrens Hosp Chicago, Div Hematol Oncol & Transplantat, Chicago, IL 60611 USA.
[Ooms, Ariadne] Erasmus MC, Josephine Nefkens Inst, Dept Pathol, NL-3000 CA Rotterdam, Netherlands.
[Gadd, Samantha; Perlman, Elizabeth J.] Northwestern Univ, Feinberg Sch Med, Lurie Childrens Hosp, Dept Pathol & Lab Med, Chicago, IL 60611 USA.
[Gadd, Samantha; Perlman, Elizabeth J.] Robert H Lurie Canc Ctr, Chicago, IL 60611 USA.
[Gerhard, Daniela S.; Auvil, Jamie M. Guidry] NCI, Off Canc Genom, Bethesda, MD 20892 USA.
[Smith, Malcolm A.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
[Meerzaman, Daoud; Chen, Qing-Rong; Hsu, Chih Hao; Yan, Chunhua; Cu Nguyen; Hu, Ying] NCI, Ctr Biomed Informat & Informat Technol, Bethesda, MD 20892 USA.
[Bowlby, Reanne; Brooks, Denise; Ma, Yussanne; Mungall, Andrew J.; Moore, Richard A.; Schein, Jacqueline; Marra, Marco A.] British Columbia Canc Agcy, Canadas Michael Smith Genome Sci Ctr, Vancouver, BC V5Z 4S6, Canada.
[Marra, Marco A.] Univ British Columbia, Dept Med Genet, Vancouver, BC V6H 3N1, Canada.
[Huff, Vicki] Univ Texas MD Anderson Canc Ctr, Dept Genet, Houston, TX 77030 USA.
[Dome, Jeffrey S.] Childrens Natl Med Ctr, Div Pediat Hematol Oncol, Washington, DC 20010 USA.
[Chi, Yueh-Yun] Univ Florida, Dept Biostat, Gainesville, FL 32610 USA.
[Mullighan, Charles G.; Ma, Jing] St Jude Childrens Res Hosp, Dept Pathol, Memphis, TN 38105 USA.
[Wheeler, David A.; Hampton, Oliver A.] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA.
[Jafari, Nadereh] Northwestern Univ, Ctr Genet Med, Chicago, IL 60611 USA.
[Ross, Nicole; Gastier-Foster, Julie M.] Ohio State Univ, Coll Med, Nationwide Childrens Hosp, Dept Pathol & Lab Med, Columbus, OH 43205 USA.
RP Perlman, EJ (reprint author), Northwestern Univ, Feinberg Sch Med, Lurie Childrens Hosp, Dept Pathol & Lab Med, Chicago, IL 60611 USA.
EM eperlman@luriechildrens.org
RI Marra, Marco/B-5987-2008;
OI Mullighan, Charles/0000-0002-1871-1850
FU NCI [U10 CA98543, T32 CA079447]; NCI, National Institutes of Health
(NIH) [HHSN261200800001E]; NIH [U10CA42326, U10CA98543, U24 CA114766,
UO1CA88131]; American and Lebanese Syrian Associated Charities of St.
Jude
FX The TARGET initiative is supported by NCI Grant U10 CA98543. Work
performed under contracts from the NCI, National Institutes of Health
(NIH), within HHSN261200800001E includes specimen processing (the COG
Biopathology Center), WGS (CGI), WXS (Baylor College of Medicine),
miRNA-seq, RNA sequencing, and target capture sequencing (British
Columbia Cancer Agency Genome Sciences Center). The content of this
publication does not necessarily reflect the views or policies of the
Department of Health and Human Services, nor does the mention of trade
names, commercial products, or organizations imply endorsement by the
USA government. We thank Patee Gesuwan and Leandro Hermida and the Data
Coordinating Center for their support. We also thank the Clinical
Applications of Core Technology Laboratory of the Hartwell Center for
Bioinformatics and Biotechnology of St. Jude Children's Research
Hospital for performing the copy number analysis and the Northwestern
University Genomic Core facility for performing the methylation
analysis. This work is also supported by NCI T32 CA079447 (A.L.W.), NIH
U10CA42326 (E.J.P.), U10CA98543 (J.S.D., E.J.P.), U24 CA114766,
UO1CA88131 (E.J.P.), and the American and Lebanese Syrian Associated
Charities of St. Jude (J.M., C.G.M.). We are grateful for the expertise
of Karen Novik and Laura Monovich, Patricia Beezhold, Donna Kersey,
Debbie-Payne Turner, Mary McNulty; and Yvonne Moyer. This work would not
be possible without the dedication of all the experts within the many
clinical disciplines at the local institutions and centrally within the
COG and the National Wilms Tumor Study Group.
NR 60
TC 30
Z9 31
U1 1
U2 9
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 FEB 9
PY 2015
VL 27
IS 2
BP 286
EP 297
DI 10.1016/j.ccell.2015.01.003
PG 12
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA CB3GC
UT WOS:000349515200014
PM 25670082
ER
PT J
AU Ratto-Kim, S
de Souza, MS
Currier, JR
Karasavvas, N
Sidney, J
Rolland, M
Valencia-Micolta, A
Madnote, S
Sette, A
Nitayaphan, S
Pitisuttuthum, P
Kaewkungwal, J
Rerks-Ngarm, S
O'Connell, R
Michael, N
Robb, ML
Marovich, M
Kim, JH
AF Ratto-Kim, Silvia
de Souza, Mark S.
Currier, Jeffrey R.
Karasavvas, Nicos
Sidney, John
Rolland, Morgane
Valencia-Micolta, Anais
Madnote, Sirinan
Sette, Alessandro
Nitayaphan, Sorachai
Pitisuttuthum, Punnee
Kaewkungwal, Jaranit
Rerks-Ngarm, Supachai
O'Connell, Robert
Michael, Nelson
Robb, Merlin L.
Marovich, Mary
Kim, Jerome H.
TI Identification of Immunodominant CD4-Restricted Epitopes Co-Located with
Antibody Binding Sites in Individuals Vaccinated with ALVAC-HIV and
AIDSVAX B/E
SO PLOS ONE
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; THAI ADULTS; SUBTYPE-B; TRIAL; V2;
IMMUNOGENICITY; EFFICACY; ENVELOPE; SAFETY; LOOP
AB We performed fine epitope mapping of the CD4+ responses in the ALVAC-HIV-AIDSVAX B/E prime-boost regimen in the Thai Phase III trial (RV144). Non-transformed Env-specific T cell lines established from RV144 vaccinees were used to determine the fine epitope mapping of the V2 and C1 responses and the HLA class II restriction. Data showed that there are two CD4+ epitopes contained within the V2 loop: one encompassing the alpha 4 beta 7 integrin binding site (AA179-181) and the other nested between two previously described genetic sieve signatures (AA169, AA181). There was no correlation between the frequencies of CD4+ fine epitope responses and binding antibody.
C1 [Ratto-Kim, Silvia; Currier, Jeffrey R.; Rolland, Morgane; Valencia-Micolta, Anais; Michael, Nelson; Robb, Merlin L.; Kim, Jerome H.] Walter Reed Army Inst Res, United States Mil HIV Res Program, Silver Spring, MD 20910 USA.
[de Souza, Mark S.; Karasavvas, Nicos; Madnote, Sirinan; O'Connell, Robert] US Army Med Component, Armed Forces Res Inst Med Sci, United States Mil HIV Res Program, Bangkok, Thailand.
[Sidney, John; Sette, Alessandro] La Jolla Inst Allergy & Immunol, La Jolla, CA 92037 USA.
[Nitayaphan, Sorachai] Armed Forces Res Inst Med Sci, Bangkok 10400, Thailand.
[Pitisuttuthum, Punnee] Mahidol Univ, Fac Trop Med, Vaccine Trials Ctr, Bangkok 10400, Thailand.
[Kaewkungwal, Jaranit] Mahidol Univ, Fac Trop Med, Ctr Excellence Biomed & Publ Hlth Informat, Bangkok 11000, Thailand.
[Rerks-Ngarm, Supachai] Minist Publ Hlth, Dept Dis Control, Nonthaburi 11000, Thailand.
[Marovich, Mary] NIH, Off AIDS Res, Bethesda, MD 20892 USA.
RP Ratto-Kim, S (reprint author), Walter Reed Army Inst Res, United States Mil HIV Res Program, Silver Spring, MD 20910 USA.
EM sratto-kim@hivresearch.org
FU Henry M. Jackson Foundation [W81XWH-07-2-0067]; U.S. Department of
Defense
FX This work was funded by the cooperative agreement (W81XWH-07-2-0067)
between the Henry M. Jackson Foundation for the Advancement of Military
Medicine and the U.S. Department of Defense. The funders had no role in
study design, data collection and analysis, decision to publish, or
preparation of the manuscript. The views expressed herein are those of
the authors and should not be construed to represent the positions of
the U.S. Army or Department of Defense.
NR 16
TC 5
Z9 5
U1 0
U2 16
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 FEB 9
PY 2015
VL 10
IS 2
AR e0115582
DI 10.1371/journal.pone.0115582
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CA7UO
UT WOS:000349123100004
PM 25665096
ER
PT J
AU Johnen, VM
Neubert, FX
Buch, ER
Verhagen, LM
O'Reilly, J
Mars, RB
Rushworth, MFS
AF Johnen, Vanessa M.
Neubert, Franz-Xaver
Buch, Ethan R.
Verhagen, Lennart M.
O'Reilly, Jill
Mars, Rogier B.
Rushworth, Matthew F. S.
TI Causal manipulation of functional connectivity in a specific neural
pathway during behaviour and at rest
SO ELIFE
LA English
DT Article
DE Resting-state connectivity; functional connectivity; premotor cortex;
fMRI; TMS; plasticity
ID VENTRAL PREMOTOR CORTEX; PRIMARY MOTOR CORTEX; TRANSCRANIAL MAGNETIC
STIMULATION; TRACTOGRAPHY-BASED PARCELLATION; PAIRED ASSOCIATIVE
STIMULATION; TRAUMATIC BRAIN-INJURY; HUMAN PARIETAL CORTEX; MACAQUE
MONKEY; FRONTAL-CORTEX; MR-IMAGES
AB Correlations in brain activity between two areas (functional connectivity) have been shown to relate to their underlying structural connections. We examine the possibility that functional connectivity also reflects short-term changes in synaptic efficacy. We demonstrate that paired transcranial magnetic stimulation (TMS) near ventral premotor cortex (PMv) and primary motor cortex (M1) with a short 8ms inter-pulse interval evoking synchronous pre- and post-synaptic activity and which strengthens interregional connectivity between the two areas in a pattern consistent with Hebbian plasticity, leads to increased functional connectivity between PMv and M1 as measured with functional magnetic resonance imaging (fMRI). Moreover, we show that strengthening connectivity between these nodes has effects on a wider network of areas, such as decreasing coupling in a parallel motor programming stream. A control experiment revealed that identical TMS pulses at identical frequencies caused no change in fMRI-measured functional connectivity when the inter-pulse-interval was too long for Hebbian-like plasticity.
C1 [Johnen, Vanessa M.; Neubert, Franz-Xaver; Verhagen, Lennart M.; Mars, Rogier B.; Rushworth, Matthew F. S.] Univ Oxford, Dept Expt Psychol, Oxford OX1 3UD, England.
[Buch, Ethan R.] NINDS, Human Cort Physiol & Neurorehabilitat Sect, NIH, Bethesda, MD 20814 USA.
[Buch, Ethan R.] Uniformed Serv Univ Hlth Sci, Ctr Neurosci & Regenerat Med, Bethesda, MD 20814 USA.
[Verhagen, Lennart M.; Mars, Rogier B.] Radboud Univ Nijmegen, Donders Inst Brain Cognit & Behav, Ctr Cognit Neuroimaging, NL-6500 HB Nijmegen, Netherlands.
[O'Reilly, Jill; Mars, Rogier B.; Rushworth, Matthew F. S.] Univ Oxford, Funct Magnet Resonance Imaging Brain FMRIB Ctr, John Radcliffe Hosp, Oxford OX3 9DU, England.
RP Johnen, VM (reprint author), Univ Oxford, Dept Expt Psychol, S Parks Rd, Oxford OX1 3UD, England.
EM vanessa.johnen@psy.ox.ac.uk
RI Verhagen, Lennart/D-1070-2013
OI Verhagen, Lennart/0000-0003-3207-7929
FU Wellcome Trust; Medical Research Council (MRC); Christopher Welch
Scholarship
FX Wellcome Trust Matthew FS Rushworth; Medical Research Council (MRC)
Matthew FS Rushworth; Christopher Welch Scholarship Franz-Xaver Neubert
NR 81
TC 4
Z9 4
U1 5
U2 9
PU ELIFE SCIENCES PUBLICATIONS LTD
PI CAMBRIDGE
PA SHERATON HOUSE, CASTLE PARK, CAMBRIDGE, CB3 0AX, ENGLAND
SN 2050-084X
J9 ELIFE
JI eLife
PD FEB 9
PY 2015
VL 4
AR e04585
DI 10.7554/eLife.04585
PG 50
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA CB2MD
UT WOS:000349460700002
ER
PT J
AU Weiss, DJ
Mappin, B
Dalrymple, U
Bhatt, S
Cameron, E
Hay, SI
Gething, PW
AF Weiss, Daniel J.
Mappin, Bonnie
Dalrymple, Ursula
Bhatt, Samir
Cameron, Ewan
Hay, Simon I.
Gething, Peter W.
TI Re-examining environmental correlates of Plasmodium falciparum malaria
endemicity: a data-intensive variable selection approach
SO MALARIA JOURNAL
LA English
DT Article
DE Plasmodium falciparum; Malaria mapping; Africa
ID LAND-COVER; IDENTIFICATION; POPULATION; WATER
AB Background: Malaria risk maps play an increasingly important role in disease control planning, implementation, and evaluation. The construction of these maps using modern geospatial techniques relies on covariate grids: continuous surfaces quantifying environmental factors that partially explain spatial heterogeneity in malaria endemicity. Although crucial, past variable selection processes for this purpose have often been subjective and ad-hoc, with many covariates used in modeling with little quantitative justification.
Methods: This research consists of an extensive covariate construction and selection process for predicting Plasmodium falciparum parasite rates (PfPR) in Africa for years 2000-2012. First, a literature review was conducted to establish a comprehensive list of covariates used for malaria mapping. Second, a library of covariate data was assembled to reflect this list, a process that included the construction of multiple, temporally dynamic datasets. Third, the resulting set of covariates was leveraged to create more than 50 million possible covariate terms via factorial combinations of different spatial and temporal aggregations, transformations, and pairwise interactions. Fourth, the expanded set of covariates was reduced via successive selection criteria to yield a robust covariate subset that was assessed using an out-of-sample validation approach.
Results: The final covariate subset included predominately dynamic covariates and it substantially out-performed earlier sets used by the Malaria Atlas Project (MAP) for creating global malaria risk maps, with the pseudo-R-2 value for the out-of-sample validation increasing from 0.43 to 0.52. Dynamic covariates improved the model, with 17 of the 20 new covariates consisting of monthly or annual products, but the selected covariates were typically interaction terms that included both dynamic and synoptic datasets. Thus the interplay between normal (i.e., long-term averages) and immediate conditions may be key for characterizing environmental controls on parasite rate.
Conclusions: This analysis represents the first effort to systematically audit covariate utility for malaria mapping and then derive an objective, empirically based set of environmental covariates for modeling PfPR. The new covariates produce more reliable representations of malaria risk patterns and how they are changing through time, and these covariates will be used to characterize spatially and temporally varying environmental conditions affecting PfPR within a geostatistical-modeling framework, thus building upon previous research by MAP that produced global malaria maps for 2007 and 2010.
C1 [Weiss, Daniel J.; Mappin, Bonnie; Dalrymple, Ursula; Bhatt, Samir; Cameron, Ewan; Hay, Simon I.; Gething, Peter W.] Univ Oxford, Dept Zool, Spatial Ecol & Epidemiol Grp, Oxford, England.
[Hay, Simon I.] Fogarty Int Ctr, NIH, Bethesda, MD USA.
RP Weiss, DJ (reprint author), Univ Oxford, Dept Zool, Spatial Ecol & Epidemiol Grp, Tinbergen Bldg, Oxford, England.
EM daniel.weiss@zoo.ox.ac.uk
RI Hay, Simon/F-8967-2015;
OI Hay, Simon/0000-0002-0611-7272; Mappin, Bonnie/0000-0002-1205-719X;
Gething, Peter/0000-0001-6759-5449
FU Bill and Melinda Gates Foundation [OPP1068048]; 943 Senior Research
Fellowship from the Wellcome Trust [095066]; RAPIDD program of the
Science & 945 Technology Directorate, Department of Homeland Security;
Fogarty 946 International Center, National Institutes of Health, USA
FX PWG is a Medical Research Council Career Development Fellow (#K00669X)
and 940 receives support from the Bill and Melinda Gates Foundation
(#OPP1068048) 941 that also supports DJW, BM, UD, SB, and EC. SIH is
funded by a 943 Senior Research Fellowship from the Wellcome Trust
(#095066) and 944 acknowledges funding support from the RAPIDD program
of the Science & 945 Technology Directorate, Department of Homeland
Security, and the Fogarty 946 International Center, National Institutes
of Health, USA.
NR 40
TC 15
Z9 15
U1 3
U2 8
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1475-2875
J9 MALARIA J
JI Malar. J.
PD FEB 7
PY 2015
VL 14
AR 68
DI 10.1186/s12936-015-0574-x
PG 18
WC Infectious Diseases; Parasitology; Tropical Medicine
SC Infectious Diseases; Parasitology; Tropical Medicine
GA CB7HQ
UT WOS:000349798000001
PM 25890035
ER
PT J
AU Coren, LV
Trivett, MT
Jain, S
Ayala, VI
Del Prete, GQ
Ohlen, C
Ott, DE
AF Coren, Lori V.
Trivett, Matthew T.
Jain, Sumiti
Ayala, Victor I.
Del Prete, Gregory Q.
Ohlen, Claes
Ott, David E.
TI Potent restriction of HIV-1 and SIVmac239 Replication by African Green
Monkey TRIM5 alpha
SO RETROVIROLOGY
LA English
DT Article
DE HIV; SIV; TRIM5 alpha; Restriction factor; Cumulative restriction
ID HUMAN-IMMUNODEFICIENCY-VIRUS; MURINE LEUKEMIA-VIRUS; TO-CELL
TRANSMISSION; SIMIAN IMMUNODEFICIENCY; RETROVIRAL RESTRICTION; REVERSE
TRANSCRIPTION; RING DOMAIN; ANTIRETROVIRAL ACTIVITY; RHESUS TRIM5-ALPHA;
TRIM5 PROTEINS
AB Background: The TRIM5 alpha protein is a principal restriction factor that contributes to an HIV-1 replication block in rhesus macaque CD4(+) T cells by preventing reverse transcription. HIV-1 restriction is induced in human CD4(+) T cells by expression of rhesus TRIM5 alpha as well as those of other old world monkeys. While TRIM5 alpha restriction has been extensively studied in single-round infection assays, fewer studies have examined restriction after extended viral replication.
Results: To examine TRIM5 alpha restriction of replication, we studied the ability of TRIM5 alpha proteins from African green monkey (AgmTRIM5 alpha) and gorilla (gorTRIM5 alpha) to restrict HIV-1 and SIVmac239 replication. These xenogeneic TRIM5 alpha genes were transduced into human Jurkat-CCR5 cells (JR5), which were then exposed to HIV-1 or SIVmac239. In our single-round infection assays, AgmTRIM5 alpha showed a relatively modest 4- to 10-fold restriction of HIV-1 and SIVmac239, while gorTRIM5 alpha produced a 2- and 3-fold restriction of HIV-1 and SIVmac239, respectively, consistent with the majority of previously published single-round studies. To assess the impact of these modest effects on infection, we tested restriction in replication systems initiated with either cell-free or cell-to-cell challenges. AgmTRIM5 alpha powerfully restricted both HIV-1 and SIVmac239 replication 14 days after cell-free infection, with a >= 3-log effect. Moreover, expression of AgmTRIM5 alpha restricted HIV-1 and SIVmac239 replication by 2-logs when co-cultured with infected JR5 cells for 12 days. In contrast, neither expression of gorTRIM5 alpha nor rhesus TRIM5 alpha induced significant resistance when co-cultured with infected cells. Follow up experiments showed that the observed differences between replication and infection were not due to assembly defects as xenogeneic TRIM5 alpha expression had no effect on either virion production or specific infectivity.
Conclusions: Our results indicate that AgmTRIM5 alpha has a much greater effect on extended replication than on any single infection event, suggesting that AgmTRIM5 alpha restriction acts cumulatively, building up over many rounds of replication. Furthermore, AgmTRIM5 alpha was able to potently restrict both HIV-1 and SIV replication in a cell-to-cell infection challenge. Thus, AgmTRIM5 alpha is unique among the TRIM5 alpha species tested to date, being able to restrict even at the high multiplicities of infection presented by mixed culture with nonrestrictive infected cells.
C1 [Coren, Lori V.; Trivett, Matthew T.; Jain, Sumiti; Ayala, Victor I.; Del Prete, Gregory Q.; Ohlen, Claes; Ott, David E.] Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, AIDS & Canc Virus Program, Frederick, MD 21702 USA.
RP Ott, DE (reprint author), Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, AIDS & Canc Virus Program, POB B, Frederick, MD 21702 USA.
EM ottde@mail.nih.gov
FU National Cancer Institute, National Institutes of Health
[HHSN261200800001E]
FX We thank Theodora Hatziioannou for the African green monkey and gorilla
TRIM5 alpha genes, Hans-Peter Kleim for the Phoenix RD114 clone 22
packaging cell line, Francois-Loic Cosset for the GAE-SFFV-GFP-WPRE
lentiviral vector DNA, and Rob Gorelick for helpful advice. The
following reagents were obtained through the NIH AIDS Reagent Program,
Division of AIDS, NIAID, NIH: Cat# 12271 Anti-rhTRIM5 alpha (3 F1-1-9),
deposited by Tom Hope and Wes Sundquist; Cat# 3444
pSIVAgmTan-1 plasmid, deposited by Marcelo Soares and
Beatrice Hahn; rhTRIM5 alpha gene, deposited by Joseph Sodroski and Matt
Stremlau; Cat# 10072; 2 F12 SIV p27 hybridoma, Cat# 1547, deposited by
Niels Pedersen. 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 86
TC 1
Z9 1
U1 0
U2 5
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1742-4690
J9 RETROVIROLOGY
JI Retrovirology
PD FEB 7
PY 2015
VL 12
AR 11
DI 10.1186/s12977-015-0137-9
PG 14
WC Virology
SC Virology
GA CC2IQ
UT WOS:000350169100001
PM 25809491
ER
PT J
AU Suzman, R
Beard, JR
Boerma, T
Chatterji, S
AF Suzman, Richard
Beard, John R.
Boerma, Ties
Chatterji, Somnath
TI Health in an ageing world-what do we know?
SO LANCET
LA English
DT Editorial Material
C1 [Suzman, Richard] NIA, Div Behav & Social Res, NIH, Bethesda, MD 20892 USA.
[Beard, John R.] WHO, Dept Ageing & Life Course, CH-1211 Geneva, Switzerland.
[Boerma, Ties; Chatterji, Somnath] WHO, Dept Hlth Stat & Informat Syst, CH-1211 Geneva, Switzerland.
RP Chatterji, S (reprint author), WHO, Dept Hlth Stat & Informat Syst, CH-1211 Geneva, Switzerland.
EM chatterjis@who.int
RI Beard, John/K-9621-2014
OI Beard, John/0000-0002-8557-0242
FU World Health Organization [001]
NR 13
TC 26
Z9 26
U1 3
U2 13
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0140-6736
EI 1474-547X
J9 LANCET
JI Lancet
PD FEB 7
PY 2015
VL 385
IS 9967
BP 484
EP 486
DI 10.1016/S0140-6736(13)61489-0
PG 4
WC Medicine, General & Internal
SC General & Internal Medicine
GA CA9AV
UT WOS:000349213600006
PM 25468156
ER
PT J
AU Lee, DW
Kochenderfer, JN
Stetler-Stevenson, M
Cui, YZK
Delbrook, C
Feldman, SA
Fry, TJ
Orentas, R
Sabatino, M
Shah, NN
Steinberg, SM
Stroncek, D
Tschemia, N
Yuan, C
Zhang, H
Zhang, L
Rosenberg, SA
Wayne, AS
Mackall, CL
AF Lee, Daniel W.
Kochenderfer, James N.
Stetler-Stevenson, Maryalice
Cui, Yongzhi K.
Delbrook, Cindy
Feldman, Steven A.
Fry, Terry J.
Orentas, Rimas
Sabatino, Marianna
Shah, Nirali N.
Steinberg, Seth M.
Stroncek, Dave
Tschemia, Nick
Yuan, Constance
Zhang, Hua
Zhang, Ling
Rosenberg, Steven A.
Wayne, Alan S.
Mackall, Crystal L.
TI T cells expressing CD19 chimeric antigen receptors for acute
lymphoblastic leukaemia in children and young adults: a phase 1
dose-escalation trial
SO LANCET
LA English
DT Article
ID C-REACTIVE PROTEIN; PEDIATRIC-PATIENTS; SURVIVAL; TRANSPLANTATION;
CLOFARABINE; MANAGEMENT; CANCER
AB Background Chimeric antigen receptor (CAR) modified T cells targeting CD19 have shown activity in case series of patients with acute and chronic lymphocytic leukaemia and B-cell lymphomas, but feasibility, toxicity, and response rates of consecutively enrolled patients treated with a consistent regimen and assessed on an intention-to-treat basis have not been reported. We aimed to define feasibility, toxicity, maximum tolerated dose, response rate, and biological correlates of response in children and young adults with refractory B-cell malignancies treated with CD19-CAR T cells.
Methods This phase 1, dose-escalation trial consecutively enrolled children and young adults (aged 1-30 years) with relapsed or refractory acute lymphoblastic leukaemia or non-Hodgkin lymphoma. Autologous T cells were engineered via an 11-day manufacturing process to express a CD19-CAR incorporating an anti-CD19 single-chain variable fragment plus TCR zeta and CD28 signalling domains. All patients received fludarabine and cyclophosphamide before a single infusion of CD19-CAR T cells. Using a standard 3 + 3 design to establish the maximum tolerated dose, patients received either 1 x 106 CAR-transduced T cells per kg (dose 1), 3 x 106 CAR-transduced T cells per kg (dose 2), or the entire CAR T-cell product if sufficient numbers of cells to meet the assigned dose were not generated. After the dose-escalation phase, an expansion cohort was treated at the maximum tolerated dose. The trial is registered with ClinicalTrials.gov, number NCT01593696.
Findings Between July 2, 2012, and June 20, 2014, 21 patients (including eight who had previously undergone allogeneic haematopoietic stem-cell transplantation) were enrolled and infused with CD19-CAR T cells. 19 received the prescribed dose of CD19-CAR T cells, whereas the assigned dose concentration could not be generated for two patients (90% feasible). All patients enrolled were assessed for response. The maximum tolerated dose was defi ned as 1 x 106 CD19-CAR T cells per kg. All toxicities were fully reversible, with the most severe being grade 4 cytokine release syndrome that occurred in three (14%) of 21 patients (95% CI 3.0-36.3). The most common non-haematological grade 3 adverse events were fever (nine [43%] of 21 patients), hypokalaemia (nine [43%] of 21 patients), fever and neutropenia (eight [38%] of 21 patients), and cytokine release syndrome (three [14%) of 21 patients).
Interpretation CD19-CAR T cell therapy is feasible, safe, and mediates potent anti-leukaemic activity in children and young adults with chemotherapy-resistant B-precursor acute lymphoblastic leukaemia. All toxicities were reversible and prolonged B-cell aplasia did not occur.
C1 [Lee, Daniel W.; Cui, Yongzhi K.; Delbrook, Cindy; Fry, Terry J.; Orentas, Rimas; Shah, Nirali N.; Zhang, Hua; Zhang, Ling; Mackall, Crystal L.] NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA.
[Kochenderfer, James N.] NCI, Transplantat & Immunol Branch, Bethesda, MD 20892 USA.
[Stetler-Stevenson, Maryalice; Yuan, Constance] NCI, Pathol Lab, Bethesda, MD 20892 USA.
[Feldman, Steven A.; Rosenberg, Steven A.] NCI, Surg Branch, Bethesda, MD 20892 USA.
[Steinberg, Seth M.] NCI, Off Clin Director, Biostat & Data Management Sect, Bethesda, MD 20892 USA.
[Sabatino, Marianna; Stroncek, Dave] NIH, Dept Transfus Med, Cell Proc Sect, Bethesda, MD 20892 USA.
[Tschemia, Nick] Univ Nevada, Sch Med, Med Student Training Program, NIH, Reno, NV 89557 USA.
[Wayne, Alan S.] Univ So Calif, Childrens Hosp Los Angeles, Keck Sch Med, Childrens Ctr Canc & Blood Dis,Div Hematol Oncol, Los Angeles, CA USA.
RP Mackall, CL (reprint author), NCI, Pediat Oncol Branch, Bldg 10,Rm 1W-3750,10 Ctr Dr MSC 1104, Bethesda, MD 20892 USA.
EM mackallc@mail.nih.gov
FU Intramural Research Program of the National Cancer Institute; St
Baldrick's Foundation Scholar Award; Stand Up To Cancer-St
Baldrick's-National Cancer Institute Pediatric Dream Team Translational
Cancer Research Gran
FX This work was supported, in part, by the Intramural Research Program of
the National Cancer Institute. DWL's work is also supported by a St
Baldrick's Foundation Scholar Award. Research was also supported by a
Stand Up To Cancer-St Baldrick's-National Cancer Institute Pediatric
Dream Team Translational Cancer Research Grant. Stand Up To Cancer is a
programme of the Entertainment Industry Foundation administered by the
American Association for Cancer Research. We would like to thank
Laurence Cooper for supplying the CD19-CAR anti-idiotype antibody, Mario
Roederer, Vaccine Research Center, National Institute of Allergy and
Infectious Diseases, National Institutes of Health, for assistance in
design of T-cell subset panels and analysis, and Linda Weaver who worked
on standardisation of methodology.
NR 34
TC 323
Z9 339
U1 29
U2 104
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0140-6736
EI 1474-547X
J9 LANCET
JI Lancet
PD FEB 7
PY 2015
VL 385
IS 9967
BP 517
EP 528
DI 10.1016/S0140-6736(14)61403-3
PG 12
WC Medicine, General & Internal
SC General & Internal Medicine
GA CA9AV
UT WOS:000349213600030
PM 25319501
ER
PT J
AU Handel, A
Lebarbenchon, C
Stallknecht, D
Rohani, P
AF Handel, Andreas
Lebarbenchon, Camille
Stallknecht, David
Rohani, Pejman
TI Trade-offs between and within scales: environmental persistence and
within-host fitness of avian influenza viruses (vol 281, 20133051, 2014)
SO PROCEEDINGS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES
LA English
DT Correction
C1 [Handel, Andreas] Univ Georgia, Coll Publ Hlth, Dept Epidemiol & Biostat, Athens, GA 30602 USA.
[Stallknecht, David] Univ Georgia, Coll Publ Hlth, Dept Populat Hlth, Athens, GA 30602 USA.
[Lebarbenchon, Camille] Univ Reunion Isl, St Denis 97715, Reunion.
[Rohani, Pejman] Univ Michigan, Dept Ecol & Evolutionary Biol, Ann Arbor, MI 48109 USA.
[Rohani, Pejman] Univ Michigan, Ctr Study Complex Syst, Ann Arbor, MI 48109 USA.
[Rohani, Pejman] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Handel, A (reprint author), Univ Georgia, Coll Publ Hlth, Dept Epidemiol & Biostat, Athens, GA 30602 USA.
NR 1
TC 0
Z9 0
U1 2
U2 15
PU ROYAL SOC
PI LONDON
PA 6-9 CARLTON HOUSE TERRACE, LONDON SW1Y 5AG, ENGLAND
SN 0962-8452
EI 1471-2954
J9 P ROY SOC B-BIOL SCI
JI Proc. R. Soc. B-Biol. Sci.
PD FEB 7
PY 2015
VL 282
IS 1800
AR 20142902
DI 10.1098/rspb.2014.2902
PG 1
WC Biology; Ecology; Evolutionary Biology
SC Life Sciences & Biomedicine - Other Topics; Environmental Sciences &
Ecology; Evolutionary Biology
GA AW6XM
UT WOS:000346409000012
ER
PT J
AU Wang, FK
Ito, Y
Wei, Y
AF Wang, Fengkang
Ito, Yoichiro
Wei, Yun
TI Recent Progress on Countercurrent Chromatography Modeling
SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES
LA English
DT Article
DE separation process; predict; peak; countercurrent chromatography; model
ID CENTRIFUGAL PARTITION CHROMATOGRAPHY; STATIONARY-PHASE; LIQUID NATURE;
ELUTION; APPARATUS; COLUMNS; FISH
AB As countercurrent chromatography is becoming an established method in chromatography for many kinds of products, it is becoming increasingly important to model the process and to be able to predict the peaks for a given process. The CCC industries are looking for rapid methods to analyze the processes of countercurrent chromatography and select a suitable solvent system. In this paper, recent progress is reviewed in the development and demonstration of several types of models of countercurrent chromatography. Literature lists a number of countercurrent chromatography (CCC) models that can predict the retention time and, to a certain extent, the peak width of a solute eluting from a CCC column, such as cell model, CCD model, CSTRs model, probabilistic model, temperature dependence plate model, physical models, and so forth.
C1 [Wang, Fengkang; Wei, Yun] Beijing Univ Chem Technol, State Key Lab Chem Resource Engn, Beijing 100029, Peoples R China.
[Ito, Yoichiro] NHLBI, Lab Bioseparat Technol, Biochem & Biophys Ctr, NIH, Bethesda, MD 20892 USA.
RP Wei, Y (reprint author), Beijing Univ Chem Technol, State Key Lab Chem Resource Engn, 15 Beisanhuan East Rd, Beijing 100029, Peoples R China.
EM weiyun@mail.buct.edu.cn
FU National Natural Science Foundation of China (NSFC) [21075007]; Program
for New Century Excellent Talents in University [NCET-11-0563]; Special
Fund for Agro-Scientific Research in the Public Interest [200803022,
201103027]; Beijing Nova Program Interdisciplinary [Z141107001814114];
Program for Changjiang Scholars and Innovative Research Team in
University [PCSIRT1205]
FX This work was supported by National Natural Science Foundation of China
(NSFC, Grant No. 21075007), Program for New Century Excellent Talents in
University (NCET-11-0563), Special Fund for Agro-Scientific Research in
the Public Interest (project 200803022 & 201103027), Beijing Nova
Program Interdisciplinary (Z141107001814114), and Program for Changjiang
Scholars and Innovative Research Team in University (PCSIRT1205).
NR 31
TC 3
Z9 3
U1 3
U2 36
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 1082-6076
EI 1520-572X
J9 J LIQ CHROMATOGR R T
JI J. Liq. Chromatogr. Relat. Technol.
PD FEB 7
PY 2015
VL 38
IS 3
SI SI
BP 415
EP 421
DI 10.1080/10826076.2014.941268
PG 7
WC Biochemical Research Methods; Chemistry, Analytical
SC Biochemistry & Molecular Biology; Chemistry
GA AR9QN
UT WOS:000343909800009
PM 25580072
ER
PT J
AU Ben-Shachar, R
Koelle, K
AF Ben-Shachar, Rotem
Koelle, Katia
TI Minimal within-host dengue models highlight the specific roles of the
immune response in primary and secondary dengue infections
SO Journal of the Royal Society Interface
LA English
DT Article
DE dengue; mathematical model; viral dynamics; immune response; cytokine
storm; disease severity
ID NECROSIS-FACTOR-ALPHA; ANTIBODY-DEPENDENT ENHANCEMENT; ORIGINAL
ANTIGENIC SIN; NATURAL-KILLER-CELLS; DYNAMICS IN-VIVO;
HEMORRHAGIC-FEVER; VIRUS-INFECTION; DISEASE SEVERITY; T-CELLS;
INTERFERON-GAMMA
AB In recent years, the within-host viral dynamics of dengue infections have been increasingly characterized, and the relationship between aspects of these dynamics and the manifestation of severe disease has been increasingly probed. Despite this progress, there are few mathematical models of within-host dengue dynamics, and the ones that exist focus primarily on the general role of immune cells in the clearance of infected cells, while neglecting other components of the immune response in limiting viraemia. Here, by considering a suite of mathematical within-host dengue models of increasing complexity, we aim to isolate the critical components of the innate and the adaptive immune response that suffice in the reproduction of several well-characterized features of primary and secondary dengue infections. By building up from a simple target cell limited model, we show that only the innate immune response is needed to recover the characteristic features of a primary symptomatic dengue infection, while a higher rate of viral infectivity (indicative of antibody-dependent enhancement) and infected cell clearance by T cells are further needed to recover the characteristic features of a secondary dengue infection. We show that these minimal models can reproduce the increased risk of disease associated with secondary heterologous infections that arises as a result of a cytokine storm, and, further, that they are consistent with virological indicators that predict the onset of severe disease, such as the magnitude of peak viraemia, time to peak viral load, and viral clearance rate. Finally, we show that the effectiveness of these virological indicators to predict the onset of severe disease depends on the contribution of T cells in fuelling the cytokine storm.
C1 [Ben-Shachar, Rotem] Duke Univ, Program Computat Biol & Bioinformat, Durham, NC 27708 USA.
[Koelle, Katia] Duke Univ, Dept Biol, Durham, NC USA.
[Koelle, Katia] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Ben-Shachar, R (reprint author), Duke Univ, Program Computat Biol & Bioinformat, Durham, NC 27708 USA.
EM rotem.ben.shachar@duke.edu
RI Barley, Kamal/F-9579-2011
OI Barley, Kamal/0000-0003-1874-9813
FU National Science Foundation [NSF-EF-08-27416]; James S. McDonnell
Foundation; RAPIDD programme of the Science and Technology Directorate,
Department of Homeland Security; Fogarty International Center, National
Institutes of Health
FX This work was funded by National Science Foundation grant no.
NSF-EF-08-27416 and by a Complex Systems grant to K.K. from the James S.
McDonnell Foundation. K.K. was further supported by the RAPIDD programme
of the Science and Technology Directorate, Department of Homeland
Security and the Fogarty International Center, National Institutes of
Health.
NR 76
TC 4
Z9 4
U1 1
U2 8
PU ROYAL SOC
PI LONDON
PA 6-9 CARLTON HOUSE TERRACE, LONDON SW1Y 5AG, ENGLAND
SN 1742-5689
EI 1742-5662
J9 J R SOC INTERFACE
JI J. R. Soc. Interface
PD FEB 6
PY 2015
VL 12
IS 103
AR UNSP 20140886
DI 10.1098/rsif.2014.0886
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CG6FY
UT WOS:000353394100003
ER
PT J
AU Nguyen, D
Rubinstein, L
Takebe, N
Miele, L
Tomaszewski, JE
Ivy, P
Doroshow, JH
Yang, SX
AF Dat Nguyen
Rubinstein, Larry
Takebe, Naoko
Miele, Lucio
Tomaszewski, Joseph E.
Ivy, Percy
Doroshow, James H.
Yang, Sherry X.
TI Notch1 phenotype and clinical stage progression in non-small cell lung
cancer
SO JOURNAL OF HEMATOLOGY & ONCOLOGY
LA English
DT Article
DE Lung cancer; N1-ICD; Notch1; NSCLC; Stage
ID EPITHELIAL-MESENCHYMAL TRANSITION; INTRACELLULAR DOMAIN; SIGNALING
PATHWAY; ADENOCARCINOMA; EXPRESSION; HYPOXIA; RELEASE; AGENTS
AB Background: Notch1 transmembrane receptor is activated through ligand-binding-triggered proteolytic cleavages and, upon release, the intracellular domain (N1-ICD) translocates into the nucleus and modulates target gene transcriptions. Notch activation has been implicated in tumorigenesis in an increasing number of human malignancies including non-small cell lung cancer (NSCLC). However, Notch1 in distinct expression patterns and activation status with tumor progression remains to be defined in NSCLC.
Methods: Notch1 and activated Notch1, N1-ICD, were examined by immunohistochemistry in 58 cases of stage I to IV NSCLC tumors. Association between Notch1 or N1-ICD expression and clinicopathological factors was assessed via correlation coefficient r statistics. P-values are two-sided.
Results: Detectable tumor Notch1, predominantly localized to the membrane and cytoplasm, was observed in 29 cases (50%, 95% Blyth-Still-Casella confidence interval 37 - 63%). It was negatively associated with stage (r = -0.43, P < 0.001) and nodal status (r = -0.33, P = 0.01), but not tumor size. In contrast, nuclear N1-ICD expression level was low and found in 12% of NSCLC patients, neither significantly associated with stage nor nodal status. Upon Notch1 activation in vitro, a mostly extra-nuclear staining was substantially turned into the nuclear signal in cancer cells.
Conclusions: Notch1 in the largely inactivated phenotype is inversely associated with clinical stage progression in NSCLC. Notch1, rather than activated N1-ICD, may be a context-dependent restrictive factor to nodal metastasis.
C1 [Dat Nguyen; Yang, Sherry X.] NCI, Natl Clin Target Validat Lab, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA.
[Rubinstein, Larry] NCI, Biometr Res Branch, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA.
[Takebe, Naoko; Ivy, Percy] NCI, Canc Therapy Evaluat Program, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA.
[Miele, Lucio] Louisiana State Univ, Hlth Sci Ctr, Stanley Scott Canc Ctr, New Orleans, LA USA.
[Miele, Lucio] Louisiana Canc Res Consortium, New Orleans, LA USA.
[Tomaszewski, Joseph E.; Doroshow, James H.] NCI, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA.
RP Yang, SX (reprint author), NCI, Natl Clin Target Validat Lab, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA.
EM Sherry.Yang@nih.gov
FU Division of Cancer Treatment and Diagnosis, National Cancer Institute,
National Institutes of Health, Bethesda, Maryland, United States
FX The Division of Cancer Treatment and Diagnosis, National Cancer
Institute, National Institutes of Health, Bethesda, Maryland, United
States in part supported this work. We are grateful to Dr. Mark Sherman
for his review of H&E stain of undifferentiated carcinoma of the ovary.
NR 34
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Z9 11
U1 0
U2 2
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1756-8722
J9 J HEMATOL ONCOL
JI J. Hematol. Oncol.
PD FEB 6
PY 2015
VL 8
AR 9
DI 10.1186/s13045-014-0104-2
PG 8
WC Oncology; Hematology
SC Oncology; Hematology
GA CD3BG
UT WOS:000350952200001
PM 25653136
ER
PT J
AU Song, Y
Hua, L
Shapiro, BA
Wang, JTL
AF Song, Yang
Hua, Lei
Shapiro, Bruce A.
Wang, Jason T. L.
TI Effective alignment of RNA pseudoknot structures using partition
function posterior log-odds scores
SO BMC BIOINFORMATICS
LA English
DT Article
DE RNA secondary structure including pseudoknots; Structural alignment;
Dynamic programming algorithm
ID MULTIPLE SEQUENCE ALIGNMENT; SECONDARY STRUCTURE PREDICTION; TURNIP
CRINKLE VIRUS; PAIRWISE ALIGNMENT; WEB SERVER; TRANSLATIONAL ENHANCER;
TERTIARY INTERACTIONS; RIBOSOME-BINDING; MESSENGER-RNA; 3D STRUCTURES
AB Background: RNA pseudoknots play important roles in many biological processes. Previous methods for comparative pseudoknot analysis mainly focus on simultaneous folding and alignment of RNA sequences. Little work has been done to align two known RNA secondary structures with pseudoknots taking into account both sequence and structure information of the two RNAs.
Results: In this article we present a novel method for aligning two known RNA secondary structures with pseudoknots. We adopt the partition function methodology to calculate the posterior log-odds scores of the alignments between bases or base pairs of the two RNAs with a dynamic programming algorithm. The posterior log-odds scores are then used to calculate the expected accuracy of an alignment between the RNAs. The goal is to find an optimal alignment with the maximum expected accuracy. We present a heuristic to achieve this goal. The performance of our method is investigated and compared with existing tools for RNA structure alignment. An extension of the method to multiple alignment of pseudoknot structures is also discussed.
Conclusions: The method described here has been implemented in a tool named RKalign, which is freely accessible on the Internet. As more and more pseudoknots are revealed, collected and stored in public databases, we anticipate a tool like RKalign will play a significant role in data comparison, annotation, analysis, and retrieval in these databases.
C1 [Song, Yang; Hua, Lei; Wang, Jason T. L.] Univ Hts, New Jersey Inst Technol, Dept Comp Sci, Bioinformat Program, Newark, NJ 07102 USA.
[Shapiro, Bruce A.] NCI, Computat RNA Struct Grp, Ctr Canc Res, Basic Res Lab, Frederick, MD 21702 USA.
RP Wang, JTL (reprint author), Univ Hts, New Jersey Inst Technol, Dept Comp Sci, Bioinformat Program, Newark, NJ 07102 USA.
EM wangj@njit.edu
FU National Science Foundation [IIS-0707571]; Intramural Research Program
of the NIH, National Cancer Institute, Center for Cancer Research
FX We are grateful to the handling editor and anonymous reviewers for their
constructive suggestions, which helped improve both the presentation and
content of this paper. We thank the developers of CARNA for providing
this robust and user-friendly tool on the web. We also thank Drs. Usman
Roshan and Kaizhong Zhang for useful conversations. This research was
supported in part by the National Science Foundation under Grant No.
IIS-0707571 and by the Intramural Research Program of the NIH, National
Cancer Institute, Center for Cancer Research.
NR 61
TC 0
Z9 0
U1 1
U2 8
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 FEB 6
PY 2015
VL 16
AR 39
DI 10.1186/s12859-015-0464-9
PG 15
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Mathematical & Computational Biology
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Mathematical & Computational Biology
GA CB8XE
UT WOS:000349914700001
PM 25727492
ER
PT J
AU Pourhoseini, S
Seth, RK
Das, S
Dattaroy, D
Kadiiska, MB
Xie, G
Michelotti, GA
Nagarkatti, M
Diehl, AM
Chatterjee, S
AF Pourhoseini, Sahar
Seth, Ratanesh Kumar
Das, Suvarthi
Dattaroy, Diptadip
Kadiiska, Maria B.
Xie, Guanhua
Michelotti, Gregory A.
Nagarkatti, Mitzi
Diehl, Anna Mae
Chatterjee, Saurabh
TI Upregulation of miR21 and Repression of Grhl3 by Leptin Mediates
Sinusoidal Endothelial Injury in Experimental Nonalcoholic
Steatohepatitis
SO PLOS ONE
LA English
DT Article
ID FATTY LIVER-DISEASE; HEPATIC STELLATE CELLS; PORTAL-HYPERTENSION;
MICRORNAS; PROGRESSION; FIBROSIS; DYSFUNCTION; EXPRESSION; NAFLD;
MECHANISMS
AB Sinusoidal endothelial dysfunction (SED) has been found to be an early event in nonalcoholic steatohepatitis (NASH) progression but the molecular mechanisms underlying its causation remains elusive. We hypothesized that adipokine leptin worsens sinusoidal injury by decreasing functionally active nitric oxide synthase 3 (NOS) 3 via miR21. Using rodent models of NASH, and transgenic mice lacking leptin and leptin receptor, results showed that hyperleptinemia caused a 4-5 fold upregulation of hepatic miR21 as assessed by qRTPCR. The upregulation of miR21 led to a time-dependent repression of its target protein Grhl3 levels as shown by western blot analyses. NOS3-p/NOS3 ratio which is controlled by Grhl3 was significantly decreased in NASH models. SED markers ICAM-1, VEGFR-2, and E-selectin as assessed by immunofluorescence microscopy were significantly up regulated in the progressive phases of NASH. Lack of leptin or its receptor in vivo, reversed the upregulation of miR21 and restored the levels of Grhl3 and NOS3-p/NOS3 ratio coupled with decreased SED dysfunction markers. Interestingly, leptin supplementation in mice lacking leptin, significantly enhanced miR21 levels, decreased Grhl3 repression and NOS3 phosphorylation. Leptin supplementation in isolated primary endothelial cells, Kupffer cells and stellate cells showed increased mir21 expression in stellate cells while sinusoidal injury was significantly higher in all cell types. Finally miR21 KO mice showed increased NOS3-p/NOS3 ratio and reversed SED markers in the rodent models of NASH. The experimental results described here show a close association of leptin-induced miR21 in aiding sinusoidal injury in NASH.
C1 [Pourhoseini, Sahar; Seth, Ratanesh Kumar; Das, Suvarthi; Dattaroy, Diptadip; Chatterjee, Saurabh] Univ S Carolina, Dept Environm Hlth Sci, Environm Hlth & Dis Lab, Columbia, SC 29208 USA.
[Kadiiska, Maria B.] Inst Environm Hlth Sci, Free Rad Metab Grp, Res Triangle Pk, NC 27709 USA.
[Xie, Guanhua; Michelotti, Gregory A.; Diehl, Anna Mae] Duke Univ, Div Gastroenterol, Durham, NC 27707 USA.
[Nagarkatti, Mitzi] Univ S Carolina, Sch Med, Dept Pathol Microbiol & Immunol, Columbia, SC 29209 USA.
RP Chatterjee, S (reprint author), Univ S Carolina, Dept Environm Hlth Sci, Environm Hlth & Dis Lab, Columbia, SC 29208 USA.
EM schatt@mailbox.sc.edu
RI Seth, Ratanesh/M-3700-2016;
OI Seth, Ratanesh/0000-0002-7078-0052; Nagarkatti,
Mitzi/0000-0002-5977-5615
FU NIH [4R00ES019875-02, R01DK053792, P20GM103641, R01AT006888,
R01ES019313]; Intramural Research Program of the National Institutes of
Health; National Institute of Environmental Health Sciences
FX This work has been supported by NIH pathway to Independence Award
(4R00ES019875-02 to Saurabh Chatterjee), NIH R01 (R01DK053792 to Anna
Mae Diehl) NIH grants (P20GM103641, R01AT006888, R01ES019313 to Mitzi
Nagarkatti) and the Intramural Research Program of the National
Institutes of Health and the National Institute of Environmental Health
Sciences. The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 55
TC 5
Z9 5
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 FEB 6
PY 2015
VL 10
IS 2
AR e0116780
DI 10.1371/journal.pone.0116780
PG 22
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CB2GK
UT WOS:000349444900065
PM 25658689
ER
PT J
AU Wilson, MM
Anderson, DE
Bernstein, HD
AF Wilson, Marlena M.
Anderson, D. Eric
Bernstein, Harris D.
TI Analysis of the Outer Membrane Proteome and Secretome of Bacteroides
fragilis Reveals a Multiplicity of Secretion Mechanisms
SO PLOS ONE
LA English
DT Article
ID GRAM-NEGATIVE BACTERIA; BINDING-PROTEIN; DEMYELINATING DISEASE;
SURFACE-PROTEINS; SIGNAL PEPTIDES; DNA INVERSIONS; GENE SEQUENCE;
CELL-ENVELOPE; IDENTIFICATION; EXPRESSION
AB Bacteroides fragilis is a widely distributed member of the human gut microbiome and an opportunistic pathogen. Cell surface molecules produced by this organism likely play important roles in colonization, communication with other microbes, and pathogenicity, but the protein composition of the outer membrane (OM) and the mechanisms used to transport polypeptides into the extracellular space are poorly characterized. Here we used LC-MS/MS to analyze the OM proteome and secretome of B. fragilis NCTC 9343 grown under laboratory conditions. Of the 229 OM proteins that we identified, 108 are predicted to be lipoproteins, and 61 are predicted to be TonB-dependent transporters. Based on their proximity to genes encoding TonB-dependent transporters, many of the lipoprotein genes likely encode proteins involved in nutrient or small molecule uptake. Interestingly, protease accessibility and biotinylation experiments indicated that an unusually large fraction of the lipoproteins are cell-surface exposed. We also identified three proteins that are members of a novel family of autotransporters, multiple potential type I protein secretion systems, and proteins that appear to be components of a type VI secretion apparatus. The secretome consisted of lipoproteins and other proteins that might be substrates of the putative type I or type VI secretion systems. Our proteomic studies show that B. fragilis differs considerably from well-studied Gram-negative bacteria such as Escherichia coli in both the spectrum of OM proteins that it produces and the range of secretion strategies that it utilizes.
C1 [Wilson, Marlena M.; Bernstein, Harris D.] NIDDK, Genet & Biochem Branch, NIH, Bethesda, MD 20892 USA.
[Anderson, D. Eric] NIDDK, Adv Mass Spectrometry Facil, NIH, Bethesda, MD 20892 USA.
RP Bernstein, HD (reprint author), NIDDK, Genet & Biochem Branch, NIH, Bethesda, MD 20892 USA.
EM harris_bernstein@nih.gov
FU National Institute of Diabetes and Digestive and Kidney Diseases
FX This study was supported by the Intramural Research 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 81
TC 13
Z9 13
U1 4
U2 33
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 FEB 6
PY 2015
VL 10
IS 2
AR e0117732
DI 10.1371/journal.pone.0117732
PG 24
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CB2GK
UT WOS:000349444900211
PM 25658944
ER
PT J
AU Welbourn, S
Kao, S
Du Pont, KE
Andrew, AJ
Berndsen, CE
Strebel, K
AF Welbourn, Sarah
Kao, Sandra
Du Pont, Kelly E.
Andrew, Amy J.
Berndsen, Christopher E.
Strebel, Klaus
TI Positioning of Cysteine Residues within the N-terminal Portion of the
BST-2/Tetherin Ectodomain Is Important for Functional Dimerization of
BST-2
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID HIV-1 VIRUS RELEASE; CELL-SURFACE; MOLECULAR-CLONING; PARTICLE RELEASE;
VPU; TETHERIN; PROTEIN; LOCALIZATION; RESTRICTION; INHIBITION
AB BST-2/tetherin is a cellular host factor capable of restricting the release of a variety of enveloped viruses, including HIV-1. Structurally, BST-2 consists of an N-terminal cytoplasmic domain, a transmembrane domain, an ectodomain, and a C-terminal membrane anchor. The BST-2 ectodomain encodes three cysteine residues in its N-terminal half, each of which can contribute to the formation of cysteine-linked dimers. We previously reported that any one of the three cysteine residues is sufficient to produce functional BST-2 dimers. Here we investigated the importance of cysteine positioning on the ectodomain for functional dimerization of BST-2. Starting with a cysteine-free monomeric form of BST-2, individual cysteine residues were reintroduced at various locations throughout the ectodomain. The resulting BST-2 variants were tested for expression, dimerization, surface presentation, and inhibition of HIV-1 virus release. We found significant flexibility in the positioning of cysteine residues, although the propensity to form cysteine-linked dimers generally decreased with increasing distance from the N terminus. Interestingly, all BST-2 variants, including the one lacking all three ectodomain cysteines, retained the ability to form non-covalent dimers, and all of the BST-2 variants were efficiently expressed at the cell surface. Importantly, not all BST-2 variants capable of forming cysteine-linked dimers were functional, suggesting that cysteine-linked dimerization of BST-2 is necessary but not sufficient for inhibiting virus release. Our results expose new structural constraints governing the functional dimerization of BST-2, a property essential to its role as a restriction factor tethering viruses to the host cell.
C1 [Welbourn, Sarah; Kao, Sandra; Andrew, Amy J.; Strebel, Klaus] NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA.
[Du Pont, Kelly E.; Berndsen, Christopher E.] James Madison Univ, Dept Chem & Biochem, Harrisonburg, VA 22807 USA.
RP Strebel, K (reprint author), NIAID, Viral Biochem Sect, Mol Microbiol Lab, NIH, Bldg 4,Rm 310,4 Ctr Dr MSC 0460, Bethesda, MD 20892 USA.
EM kstrebel@nih.gov
OI Berndsen, Christopher/0000-0002-4285-4341
FU Intramural Research Program of the NIAID, National Institutes of Health
[1 ZO1 AI000669]; Canadian Institutes of Health Research; Research
Corporation Development Award [7957]; James Madison University Program
of Grants for Faculty Assistance; 4-VA organization
FX This work was supported in part by the Intramural Research Program of
the NIAID, National Institutes of Health Grant 1 ZO1 AI000669.;
Supported by a postdoctoral fellowship from the Canadian Institutes of
Health Research.; Supported by Research Corporation Development Award
7957, the James Madison University Program of Grants for Faculty
Assistance, and the 4-VA organization.
NR 34
TC 2
Z9 2
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 FEB 6
PY 2015
VL 290
IS 6
BP 3740
EP 3751
DI 10.1074/jbc.M114.617639
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA CB2KL
UT WOS:000349456000045
PM 25525265
ER
PT J
AU Weisz, A
Ridge, CD
Mazzola, EP
Ito, Y
AF Weisz, Adrian
Ridge, Clark D.
Mazzola, Eugene P.
Ito, Yoichiro
TI Preparative separation and identification of novel subsidiary colors of
the color additive D&C Red No. 33 (Acid Red 33) using spiral high-speed
counter-current chromatography
SO JOURNAL OF CHROMATOGRAPHY A
LA English
DT Article
DE D&C Red No. 33; Spiral high-speed counter-current chromatography; NMR
spectra of dye impurities;
5-Amino-3-biphenyl-3-ylazo-4-hydroxy-naphthalene-2,7-disulfonic acid;
5-Amino-4-hydroxy-6-phenyl-3-phenylazo-naphthalene-2,7-disulfonic acid;
5-Amino-4-hydroxy-3,6-bis-phenylazo-naphthalene-2,7-disulfonic acid
ID PERFORMANCE LIQUID-CHROMATOGRAPHY; SOLID-PHASE MICROEXTRACTION; TUBING
SUPPORT ROTOR; MASS-SPECTROMETRY; PHLOXINE-B; NOS. 27; QUINOLINE YELLOW;
BASE EQUILIBRIA; AZO-HYDRAZONE; 5 TARTRAZINE
AB Three low-level subsidiary color impurities (A, B, and C) often present in batches of the color additive D&C Red No. 33 (R33, Acid Red 33, Colour Index No. 17200) were separated from a portion of R33 by spiral high-speed counter-current chromatography (HSCCC). The separation involved use of a very polar solvent system, 1-BuOH/5 mM aq. (NH4)(2)SO4. Addition of ammonium sulfate to the lower phase forced partition of the components into the upper phase, thereby eliminating the need to add a hydrophobic counterion as was previously required for separations of components from sulfonated dyes. The very polar solvent system used would not have been retained in a conventional multi-layer coil HSCCC instrument, but the spiral configuration enabled retention of the stationary phase, and thus, the separation was possible. A 1 g portion of R33 enriched in A, B, and C was separated using the upper phase of the solvent system as the mobile phase. The retention of the stationary phase was 38.1%, and the separation resulted in 4.8 mg of A of >90% purity, 18.3 mg of B of >85% purity, and 91 mg of C of 65-72% purity. A second separation of a portion of the C mixture resulted in 7 mg of C of >94% purity. The separated impurities were identified by high-resolution mass spectrometry and NMR spectroscopic techniques as follows: 5-amino-3-bipheny1-3-ylazo-4-hydroxy-naphthalene2,7-disulfonic acid, A; 5-amino-4-hydroxy-6-pheny1-3-phenylazo-naphthalene-2,7-disulfonic acid, B; and 5-amino-4-hydroxy-3,6-bis-phenylazo-naphthalene-2,7-disulfonic acid, C. The isomers A and B are compounds reported for the first time. Application of the spiral HSCCC method resulted in the additional benefit of yielding 930 mg of the main component of R33, 5-amino-4-hydroxy-3-phenylazo-naphthalene2,7-disulfonic acid, of >97% purity. Published by Elsevier B.V.
C1 [Weisz, Adrian] US FDA, Off Cosmet & Colors, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA.
[Ridge, Clark D.; Mazzola, Eugene P.] US FDA, Off Regulatory Sci, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA.
[Ito, Yoichiro] NHLBI, Bioseparat Technol Lab, Biochem & Biophys Ctr, NIH, Bethesda, MD 20892 USA.
RP Weisz, A (reprint author), US FDA, Off Cosmet & Colors, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA.
EM adrian.weisz@fda.hhs.gov
FU Intramural NIH HHS [ZIA HL005107-07]
NR 48
TC 3
Z9 3
U1 2
U2 23
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0021-9673
EI 1873-3778
J9 J CHROMATOGR A
JI J. Chromatogr. A
PD FEB 6
PY 2015
VL 1380
BP 120
EP 129
DI 10.1016/j.chroma.2014.12.072
PG 10
WC Biochemical Research Methods; Chemistry, Analytical
SC Biochemistry & Molecular Biology; Chemistry
GA CA4RW
UT WOS:000348893100015
PM 25591404
ER
PT J
AU Hickman, HD
AF Hickman, Heather D.
TI There goes the macrophage neighborhood
SO SCIENCE
LA English
DT Editorial Material
ID SUBCAPSULAR SINUS MACROPHAGES; CD8(+) T-CELLS; DENDRITIC CELLS;
LYMPH-NODES; B-CELLS; VIRUS
C1 NIH, Bethesda, MD 20892 USA.
RP Hickman, HD (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA.
EM hhickman@mail.nih.gov
FU Intramural NIH HHS
NR 12
TC 0
Z9 0
U1 1
U2 8
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 FEB 6
PY 2015
VL 347
IS 6222
BP 609
EP 610
DI 10.1126/science.aaa6919
PG 2
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CA8CX
UT WOS:000349145200021
PM 25657230
ER
PT J
AU Lecchi, A
Razzari, C
Paoletta, S
Dupuis, A
Nakamura, L
Ohlmann, P
Gachet, C
Jacobson, KA
Zieger, B
Cattaneo, M
AF Lecchi, Anna
Razzari, Cristina
Paoletta, Silvia
Dupuis, Arnaud
Nakamura, Lea
Ohlmann, Philippe
Gachet, Christian
Jacobson, Kenneth A.
Zieger, Barbara
Cattaneo, Marco
TI Identification of a new dysfunctional platelet P2Y(12) receptor variant
associated with bleeding diathesis
SO BLOOD
LA English
DT Article
ID LIGHT TRANSMISSION AGGREGOMETRY; DRUG-INDUCED DEFECTS;
ADENOSINE-DIPHOSPHATE; RICH PLASMA; PATIENT; ADP; AGGREGATION; MUTATION;
COMPLEX; PROTEIN
AB Defects of the platelet P2Y(12) receptor (P2Y(12)R) for adenosine diphosphate (ADP) are associated with increased bleeding risk. The study of molecular abnormalities associated with inherited qualitative defects of the P2Y(12)R protein is useful to unravel structure-function relationships of the receptor. We describe the case of 2 brothers, sons of first cousins, with lifelong history of abnormal bleeding, associated with dysfunctional P2Y(12)R and a previously undescribed missense mutation in the encoding gene. ADP (4-20 mu M)-induced aggregation of patients' platelets was markedly reduced and rapidly reversible. Other agonists induced borderline-normal aggregation. Inhibition of vasodilator-stimulated phosphoprotein phosphorylation and prostaglandin E-1-induced increase in cyclic adenosine monophosphate (cAMP) by ADP was impaired, whereas inhibition of cAMP increase by epinephrine was normal. [H-3]PSB-0413, a selective P2Y(12)R antagonist, bound to a normal number of binding sites; however, its affinity, and that of the agonists ADP and 2-methylthio-adenosine-5'-diphosphate, was reduced. Patients' DNA showed a homozygous c.847T>A substitution that changed the codon for His-187 to Gln (p.His187Gln). Crystallographic data and molecular modeling studies indicated that His187 in transmembrane 5 is important for agonist and nucleotide antagonist binding and located in a region undergoing conformational changes. These studies delineate a region of P2Y(12)R required for normal function after ADP binding.
C1 [Lecchi, Anna] Osped Maggiore Policlin, Fdn Ist Ricovero & Cura Carattere Sci Ca Granda, Angelo Bianchi Bonomi Hemophilia & Thrombosis Ctr, Milan, Italy.
[Razzari, Cristina; Cattaneo, Marco] Univ Milan, Osped San Paolo, Dipartimento Sci Salute, Div Med 3, I-20142 Milan, Italy.
[Paoletta, Silvia; Jacobson, Kenneth A.] NIDDK, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
[Dupuis, Arnaud; Ohlmann, Philippe; Gachet, Christian] Univ Strasbourg, Unite Mixte Rech S949, Etab Francais Sang Alsace, Strasbourg, France.
[Nakamura, Lea; Zieger, Barbara] Univ Med Ctr Freiburg, Dept Pediat & Adolescent Med, Freiburg, Germany.
RP Cattaneo, M (reprint author), Univ Milan, Osped San Paolo, Unita Med 3, Via Rudini 8, I-20142 Milan, Italy.
EM marco.cattaneo@unimi.it
RI Jacobson, Kenneth/A-1530-2009; Gachet, Christian/H-9156-2016;
OI Jacobson, Kenneth/0000-0001-8104-1493; Cattaneo,
Marco/0000-0002-7343-4534
FU National Institutes of Health National Institute of Diabetes and
Digestive Kidney Diseases Intramural Research Program
FX This work was supported by the National Institutes of Health National
Institute of Diabetes and Digestive Kidney Diseases Intramural Research
Program (K.A.J. and S.P.).
NR 31
TC 12
Z9 13
U1 0
U2 2
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 FEB 5
PY 2015
VL 125
IS 6
BP 1006
EP 1013
DI 10.1182/blood-2013-07-517896
PG 8
WC Hematology
SC Hematology
GA CD1ES
UT WOS:000350817700019
PM 25428217
ER
PT J
AU Fennell, TR
Morgan, DL
Watson, SL
Dhungana, S
Waidyanatha, S
AF Fennell, Timothy R.
Morgan, Daniel L.
Watson, Scott L.
Dhungana, Suraj
Waidyanatha, Suramya
TI Systemic uptake, albumin and hemoglobin binding of [C-14]2,3-butanedione
administered by intratracheal instillation in male Harlan Sprague Dawley
rats and oropharyngeal aspiration in male B6C3F(1)/N mice
SO CHEMICO-BIOLOGICAL INTERACTIONS
LA English
DT Article
DE 2,3-Butanedione; Hemoglobin binding; Albumin binding; Systemic uptake
ID INHALATION DOSIMETRY; BUTTER FLAVORANT; DIACETYL; METHYLGLYOXAL;
PROTEINS; MODEL; 2,3-BUTANEDIONE; BRONCHIOLITIS; HYPERGLYCEMIA;
ACETALDEHYDE
AB 2,3-Butanedione (BD) is a reactive diketone in artificial butter flavors that is thought to cause bronchiolitis obliterans in workers in microwave popcorn manufacturing. Bronchiolitis obliterans is generally not diagnosed until irreversible damage has occurred; therefore a biomarker of early exposure is needed. The potential systemic uptake of BD from inhalation exposure has not been evaluated. The objective here was to evaluate the systemic exposure of BD and binding to hemoglobin and albumin. [C-14]BD was administered to male Harlan Sprague Dawley rats (100 mg/kg, intratracheal instillation) and B6C3F(1/N) mice (157 mg/kg, oropharyngeal aspiration). Blood and plasma was collected 24 h after administration and analyzed for C-14 content. At 24 h, 0.88 +/- 0.07% of the administered dose was in rat blood, 0.66 +/- 0.06% in rat plasma, 0.38 +/- 0.13% in mouse blood and 0.17 +/- 0.05% in mouse plasma. Albumin binding in rats was 269 +/- 24.2 ng equiv./mg, which accounts for 38% of the radioactivity in plasma. In mice, binding was 85.0 +/- 22.3 ng equiv./mg albumin, which accounts for 51% of the radioactivity in plasma. The binding to hemoglobin in rats was 38.2 +/- 17.6 ng equiv./mg, and to globin was 29.1 +/- 3.96 ng equiv./mg. In mice, the binding to hemoglobin was 16.2 +/- 9.0 ng equiv./mg. The site(s) of adduction on hemoglobin and albumin was investigated by mass spectrometry. In rat globin, arginine adducts were detected at R-30 and R-104 of the beta chain in vitro and in vivo. In rat albumin, adducts were detected in vitro on R-219/221, R-360, and R-368, and in vivo on a variety of arginine residues. This study demonstrated that BD enters the systemic circulation and reacts with arginine on hemoglobin and albumin. These results indicate that hemoglobin and albumin adducts may be useful as biomarkers of BD exposure in humans. (C) 2014 Elsevier Ireland Ltd. All rights reserved.
C1 [Fennell, Timothy R.; Watson, Scott L.; Dhungana, Suraj] RTI Int, Res Triangle Pk, NC USA.
[Morgan, Daniel L.; Waidyanatha, Suramya] NIEHS, Div Natl Toxicol Program, Res Triangle Pk, NC 27709 USA.
RP Waidyanatha, S (reprint author), NIEHS, Program Operat Branch, Div Natl Toxicol Program, POB 12233,MD K2-07, Res Triangle Pk, NC 27709 USA.
EM waidyanathas@niehs.nih.gov
FU National Toxicology Program, National Institute of Environmental Health
Sciences, National Institutes of Health, U.S. Department of Health and
Human Services [N01-ES-75563 (HHSN29120077563)]
FX This work was performed for the National Toxicology Program, National
Institute of Environmental Health Sciences, National Institutes of
Health, U.S. Department of Health and Human Services, under contract No.
N01-ES-75563 (HHSN29120077563).
NR 23
TC 2
Z9 2
U1 1
U2 7
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0009-2797
EI 1872-7786
J9 CHEM-BIOL INTERACT
JI Chem.-Biol. Interact.
PD FEB 5
PY 2015
VL 227
BP 112
EP 119
DI 10.1016/j.cbi.2014.12.029
PG 8
WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology
GA CC1GE
UT WOS:000350088400014
PM 25559854
ER
PT J
AU Maier, R
Moser, G
Chen, GB
Ripke, S
Coryell, W
Potash, JB
Scheftner, WA
Shi, JX
Weissman, MM
Hultman, CM
Landen, M
Levinson, DF
Kendler, KS
Smoller, JW
Wray, NR
Lee, SH
AF Maier, Robert
Moser, Gerhard
Chen, Guo-Bo
Ripke, Stephan
Coryell, William
Potash, James B.
Scheftner, William A.
Shi, Jianxin
Weissman, Myrna M.
Hultman, Christina M.
Landen, Mikael
Levinson, Douglas F.
Kendler, Kenneth S.
Smoller, Jordan W.
Wray, Naomi R.
Lee, S. Hong
CA Psychiat Genomics Consortium
TI Joint Analysis of Psychiatric Disorders Increases Accuracy of Risk
Prediction for Schizophrenia, Bipolar Disorder, and Major Depressive
Disorder
SO AMERICAN JOURNAL OF HUMAN GENETICS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; RESTRICTED MAXIMUM-LIKELIHOOD; AVERAGE
INFORMATION; GENETIC RISK; LOCI; SELECTION; TRAITS; MODELS;
IDENTIFICATION; POPULATION
AB Genetic risk prediction has several potential applications in medical research and clinical practice and could be used, for example, to stratify a heterogeneous population of patients by their predicted genetic risk. However, for polygenic traits, such as psychiatric disorders, the accuracy of risk prediction is low. Here we use a multivariate linear mixed model and apply multi-trait genomic best linear unbiased prediction for genetic risk prediction. This method exploits correlations between disorders and simultaneously evaluates individual risk for each disorder. We show that the multivariate approach significantly increases the prediction accuracy for schizophrenia, bipolar disorder, and major depressive disorder in the discovery as well as in independent validation datasets. By grouping SNPs based on genome annotation and fitting multiple random effects, we show that the prediction accuracy could be further improved. The gain in prediction accuracy of the multivariate approach is equivalent to an increase in sample size of 34% for schizophrenia, 68% for bipolar disorder, and 76% for major depressive disorders using single trait models. Because our approach can be readily applied to any number of GWAS datasets of correlated traits, it is a flexible and powerful tool to maximize prediction accuracy. With current sample size, risk predictors are not useful in a clinical setting but already are a valuable research tool, for example in experimental designs comparing cases with high and low polygenic risk.
C1 [Maier, Robert; Moser, Gerhard; Chen, Guo-Bo; Wray, Naomi R.; Lee, S. Hong] Univ Queensland, Queensland Brain Inst, Brisbane, Qld 4072, Australia.
[Ripke, Stephan] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA.
[Coryell, William; Potash, James B.] Univ Iowa, Dept Psychiat, Iowa City, IA 52242 USA.
[Scheftner, William A.] Rush Univ, Dept Psychiat, Med Ctr, Chicago, IL 60612 USA.
[Shi, Jianxin] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Weissman, Myrna M.] Columbia Univ, Dept Psychiat, New York, NY 10032 USA.
[Weissman, Myrna M.] New York State Psychiat Inst & Hosp, New York, NY 10032 USA.
[Hultman, Christina M.; Landen, Mikael] Karolinska Inst, Dept Med Epidemiol & Biostat, S-17177 Stockholm, Sweden.
[Landen, Mikael] Gothenburg Univ, Sahlgrenska Acad, Inst Neurosci & Physiol, S-41345 Gothenburg, Sweden.
[Levinson, Douglas F.] Stanford Univ, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA.
[Kendler, Kenneth S.] Virginia Commonwealth Univ, Virginia Inst Psychiat & Behav Genet, Dept Psychiat, Richmond, VA 23298 USA.
[Smoller, Jordan W.] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Ctr Human Genet Res, Boston, MA 02114 USA.
RP Lee, SH (reprint author), Univ Queensland, Queensland Brain Inst, Brisbane, Qld 4072, Australia.
EM hong.lee@uq.edu.au
RI Hansen, Thomas Folkmann/O-5965-2014; Lohoff, Falk/M-7951-2016;
BELLIVIER, FRANK/H-5197-2012; McQuillin, Andrew/C-1623-2008; Lesch,
Klaus-Peter/J-4906-2013; Wray, Naomi/C-8639-2015; Ruderfer,
Douglas/M-5795-2016; Scherer, Stephen /B-3785-2013; Lee, Sang
Hong/A-2569-2011; Kuntsi, Jonna/G-9750-2011; Franke,
Barbara/D-4836-2009; Moser, Gerhard/H-7054-2012; Collier,
David/D-1649-2011; Zhang, Peng/N-2920-2014; Mattheisen,
Manuel/B-4949-2012; Breen, Gerome/A-5540-2010; Melle, Ingrid
/B-4858-2011; Schumacher, Johannes/F-4970-2015
OI Yu, Timothy/0000-0003-2988-7701; Thapar, Anita/0000-0002-3689-737X;
Etain, Bruno/0000-0002-5377-1488; de Geus, Eco/0000-0001-6022-2666;
Chen, Guo-Bo/0000-0001-5475-8237; Cormand, Bru/0000-0001-5318-4382;
Betancur, Catalina/0000-0002-3327-4804; Jamain,
Stephane/0000-0002-4321-4100; Weissman, Myrna/0000-0003-3490-3075;
Hansen, Thomas Folkmann/0000-0001-6703-7762; Kent,
Lindsey/0000-0002-5315-3399; Anney, Richard/0000-0002-6083-407X;
Bruggeman, Richard/0000-0002-3238-8471; Nothen,
Markus/0000-0002-8770-2464; Donohoe, Gary/0000-0003-3037-7426; Oliveira,
Guiomar/0000-0002-7049-1277; McQuillin, Andrew/0000-0003-1567-2240;
Lesch, Klaus-Peter/0000-0001-8348-153X; Bergen,
Sarah/0000-0002-5888-0034; Backlund, Lena/0000-0001-9399-5024; Zammit,
Stanley/0000-0002-2647-9211; McMahon, Francis/0000-0002-9469-305X;
Hamilton, Steven/0000-0001-8106-6260; Gallagher,
Louise/0000-0001-9462-2836; Tozzi, Federica/0000-0002-3536-2920;
Myin-Germeys, Inez/0000-0002-3731-4930; Wray, Naomi/0000-0001-7421-3357;
Ruderfer, Douglas/0000-0002-2365-386X; Scherer, Stephen
/0000-0002-8326-1999; Lee, Sang Hong/0000-0001-9701-2718; Franke,
Barbara/0000-0003-4375-6572; Moser, Gerhard/0000-0003-3104-5730;
Collier, David/0000-0003-4087-1559; Zhang, Peng/0000-0003-1182-1392;
Mattheisen, Manuel/0000-0002-8442-493X; Breen,
Gerome/0000-0003-2053-1792; Melle, Ingrid /0000-0002-9783-548X;
Schumacher, Johannes/0000-0001-9217-6457
FU Australian Research Council [FT0991360, DE130100614]; National Health
and Medical Research Council [613608, 1011506, 1047956, 1080157];
National Institute of Mental Health (NIMH) [U01 MH085520]; Stanley
Center for Psychiatric Research; Sylvan Herman Foundation; Karolinska
Institutet, Karolinska University Hospital; Swedish Research Council;
Stockholm County Council; Soderstrom Konigska Foundation; Netherlands
Scientific Organization [NWO 645-000-003]; Netherlands Scientific
Organization (NOW) [480-05-003]; NIMH R01 [MH061686, MH059542, MH075131,
MH059552, MH059541, MH060912]; [NIMH R01 MH077139]
FX This study was supported by the Australian Research Council (FT0991360
and DE130100614) and the National Health and Medical Research Council
(613608, 1011506, 1047956, and 1080157). The Psychiatric Genomics
Consortium is supported by National Institute of Mental Health (NIMH)
grant U01 MH085520. We acknowledge the funding that supported the
Swedish schizophrenia study (NIMH R01 MH077139), the Stanley Center for
Psychiatric Research, the Sylvan Herman Foundation, the Karolinska
Institutet, Karolinska University Hospital, the Swedish Research
Council, the Stockholm County Council, the Soderstrom Konigska
Foundation, and the Netherlands Scientific Organization (NWO
645-000-003). Statistical analyses were carried out on the Genetic
Cluster Computer, which is financially supported by the Netherlands
Scientific Organization (NOW; 480-05-003). The GenRED GWAS project was
supported by NIMH R01 grants MH061686 (D.F.L.), MH059542 (W.C.),
MH075131 (W.B. Lawson), MH059552 (J.B.P.), MH059541 (W.A.S.), and
MH060912 (M.M.W.).
NR 45
TC 38
Z9 38
U1 6
U2 43
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0002-9297
EI 1537-6605
J9 AM J HUM GENET
JI Am. J. Hum. Genet.
PD FEB 5
PY 2015
VL 96
IS 2
BP 283
EP 294
DI 10.1016/j.ajhg.2014.12.006
PG 12
WC Genetics & Heredity
SC Genetics & Heredity
GA CA9WY
UT WOS:000349276700010
PM 25640677
ER
PT J
AU Diaz-Ruiz, A
Gonzalez-Freire, M
Ferrucci, L
Bernier, M
de Cabo, R
AF Diaz-Ruiz, Alberto
Gonzalez-Freire, Marta
Ferrucci, Luigi
Bernier, Michel
de Cabo, Rafael
TI SIRT1 Synchs Satellite Cell Metabolism with Stem Cell Fate
SO CELL STEM CELL
LA English
DT Editorial Material
AB Metabolic reprogramming of muscle stem cells modulates myogenic cell fate. In this issue of Cell Stem Cell, Ryall et al. (2015) show that SIRT1, a NAD(+)- dependent histone deacetylase, acts as an epigenetic regulator that connects changes in satellite cell metabolism with changes in the transcriptional machinery toward myogenic commitment.
C1 [Diaz-Ruiz, Alberto; Gonzalez-Freire, Marta; Ferrucci, Luigi; Bernier, Michel; de Cabo, Rafael] NIA, Expt Gerontol Sect, Translat Gerontol Branch, NIH, Baltimore, MD 21224 USA.
RP de Cabo, R (reprint author), NIA, Expt Gerontol Sect, Translat Gerontol Branch, NIH, Baltimore, MD 21224 USA.
EM deCaboRa@mail.nih.gov
RI de Cabo, Rafael/J-5230-2016;
OI de Cabo, Rafael/0000-0002-3354-2442; Bernier,
Michel/0000-0002-5948-368X; , rafael/0000-0003-2830-5693
FU Intramural NIH HHS
NR 10
TC 2
Z9 3
U1 0
U2 5
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1934-5909
EI 1875-9777
J9 CELL STEM CELL
JI Cell Stem Cell
PD FEB 5
PY 2015
VL 16
IS 2
BP 103
EP 104
DI 10.1016/j.stem.2015.01.006
PG 2
WC Cell & Tissue Engineering; Cell Biology
SC Cell Biology
GA CB2KC
UT WOS:000349455000001
PM 25658362
ER
PT J
AU Ryall, JG
Dell'Orso, S
Derfoul, A
Juan, A
Zare, H
Feng, XS
Clermont, D
Koulnis, M
Gutierrez-Cruz, G
Fulco, M
Sartorelli, V
AF Ryall, James G.
Dell'Orso, Stefania
Derfoul, Assia
Juan, Aster
Zare, Hossein
Feng, Xuesong
Clermont, Daphney
Koulnis, Miroslav
Gutierrez-Cruz, Gustavo
Fulco, Marcella
Sartorelli, Vittorio
TI The NAD(+)-Dependent SIRT1 Deacetylase Translates a Metabolic Switch
into Regulatory Epigenetics in Skeletal Muscle Stem Cells
SO CELL STEM CELL
LA English
DT Article
ID SATELLITE CELLS; SELF-RENEWAL; TRANSCRIPTION FACTORS; REGENERATION;
DIFFERENTIATION; MYOGENESIS; QUIESCENT; SIRTUINS; ACETYLATION; NICHE
AB Stem cells undergo a shift in metabolic substrate utilization during specification and/or differentiation, a process that has been termed metabolic reprogramming. Here, we report that during the transition from quiescence to proliferation, skeletal muscle stem cells experience a metabolic switch from fatty acid oxidation to glycolysis. This reprogramming of cellular metabolism decreases intracellular NAD(+) levels and the activity of the histone deacetylase SIRT1, leading to elevated H4K16 acetylation and activation of muscle gene transcription. Selective genetic ablation of the SIRT1 deacetylase domain in skeletal muscle results in increased H4K16 acetylation and deregulated activation of the myogenic program in SCs. Moreover, mice with muscle-specific inactivation of the SIRT1 deacetylase domain display reduced myofiber size, impaired muscle regeneration, and derepression of muscle developmental genes. Overall, these findings reveal how metabolic cues can be mechanistically translated into epigenetic modifications that regulate skeletal muscle stem cell biology.
C1 [Ryall, James G.; Dell'Orso, Stefania; Derfoul, Assia; Juan, Aster; Zare, Hossein; Feng, Xuesong; Clermont, Daphney; Koulnis, Miroslav; Gutierrez-Cruz, Gustavo; Fulco, Marcella; Sartorelli, Vittorio] NIAMSD, Lab Muscle Stem Cells & Gene Regulat, NIH, Bethesda, MD 20829 USA.
RP Sartorelli, V (reprint author), NIAMSD, Lab Muscle Stem Cells & Gene Regulat, NIH, Bethesda, MD 20829 USA.
EM sartorev@mail.nih.gov
OI Ryall, James/0000-0003-4702-1143
FU Overseas Biomedical Research Fellowship from the National Health &
Medical Research Council of Australia; Intramural Research Program of
NIAMS at the NIH
FX We thank Yansong Gu (University of Washington, Seattle) for sharing the
Sirt1 floxed mice, Kristina Zaal (Light Imaging Section, National
Institute of Arthritis and Musculoskeletal and Skin Diseases [NIAMS])
for help in evaluating Pax7+/MyoD+
immunofluorescence staining, and Jim Simone (Flow Cytometry Section,
NIAMS) for help with FACS. J.G.R. was supported, in part, via an
Overseas Biomedical Research Fellowship from the National Health &
Medical Research Council of Australia. This work was supported by the
Intramural Research Program of NIAMS at the NIH.
NR 56
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U1 8
U2 25
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1934-5909
EI 1875-9777
J9 CELL STEM CELL
JI Cell Stem Cell
PD FEB 5
PY 2015
VL 16
IS 2
BP 171
EP 183
DI 10.1016/j.stem.2014.12.004
PG 13
WC Cell & Tissue Engineering; Cell Biology
SC Cell Biology
GA CB2KC
UT WOS:000349455000013
PM 25600643
ER
PT J
AU Wu, D
Minton, AP
AF Wu, Di
Minton, Allen P.
TI Quantitative Characterization of Nonspecific Self- and
Hetero-Interactions of Proteins in Nonideal Solutions via Static Light
Scattering
SO JOURNAL OF PHYSICAL CHEMISTRY B
LA English
DT Article
ID TRIMETHYLAMINE-N-OXIDE; INTERMOLECULAR INTERACTIONS; ASSOCIATING
PROTEINS; RIBONUCLEASE; MIXTURES; DISSOCIATION
AB The dependence of static light scattering upon the compositions of solutions including hen egg white ovalbumin, hen egg white ovomucoid, ribonuclease A, and binary mixtures of these proteins at total concentrations of up to about 40 g/L were measured at different values of the pH and ionic strength. At the pH values of measurement, ovalbumin and ovomucoid have a net negative charge and ribonuclease A has a net positive charge. The observed dependence of scattering intensity upon solution composition may be accounted for by an extension of previously formulated equivalent hard particle models that allows for the presence of both repulsive interactions between like species and attractive interactions between unlike species in mixtures of positively and negatively charged proteins.
C1 [Wu, Di; Minton, Allen P.] NIDDK, Sect Phys Biochem, Lab Biochem & Genet, NIH,US Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
RP Minton, AP (reprint author), NIH, Bldg 8,Room 226, Bethesda, MD 20892 USA.
EM minton@helix.nih.gov
OI Minton, Allen/0000-0001-8459-1247
FU National Institute of Diabetes and Digestive and Kidney Diseases
FX The authors thank Dr. Xiao-nan Zhao (NIDDK) for the electrophoresis
experiments and thank Dr. Peter McPhie (NTH) for a critical reading of
the draft manuscript. This research was supported by the Intramural
Research Program of the National Institute of Diabetes and Digestive and
Kidney Diseases.
NR 32
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Z9 4
U1 1
U2 10
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 FEB 5
PY 2015
VL 119
IS 5
BP 1891
EP 1898
DI 10.1021/jp510918d
PG 8
WC Chemistry, Physical
SC Chemistry
GA CA7ZT
UT WOS:000349137000011
PM 25580677
ER
PT J
AU Huang, R
Xu, YF
Wan, W
Shou, X
Qian, JL
You, ZY
Liu, B
Chang, CM
Zhou, TH
Lippincott-Schwartz, J
Liu, W
AF Huang, Rui
Xu, Yinfeng
Wan, Wei
Shou, Xin
Qian, Jiali
You, Zhiyuan
Liu, Bo
Chang, Chunmei
Zhou, Tianhua
Lippincott-Schwartz, Jennifer
Liu, Wei
TI Deacetylation of Nuclear LC3 Drives Autophagy Initiation under
Starvation
SO MOLECULAR CELL
LA English
DT Article
ID MICROTUBULE-ASSOCIATED PROTEIN-1; SMOOTH-MUSCLE-CELLS; LIGHT-CHAIN 3;
ENDOPLASMIC-RETICULUM; STRUCTURAL BASIS; MAMMALIAN-CELLS; COMPLEX; ATG8;
ACETYLTRANSFERASE; PHOSPHORYLATION
AB Shuttling of macromolecules between different cellular compartments helps regulate the timing and extent of different cellular activities. Here, we report that LC3, a key initiator of autophagy that cycles between the nucleus and cytoplasm, becomes selectively activated in the nucleus during starvation through deacetylation by the nuclear deacetylase Sirt1. Deacetylation of LC3 at K49 and K51 by Sirt1 allows LC3 to interact with the nuclear protein DOR and return to the cytoplasm with DOR, where it is able to bind Atg7 and other autophagy factors and undergo phosphatidylethanolamine conjugation to preautophagic membranes. The association of deacetylated LC3 with autophagic factors shifts LC3's distribution from the nucleus toward the cytoplasm. Thus, an acetylation-deacetylation cycle ensures that LC3 effectively redistributes in an activated form from nucleus to cytoplasm, where it plays a central role in autophagy to enable the cell to cope with the lack of external nutrients.
C1 [Huang, Rui; Xu, Yinfeng; Wan, Wei; Shou, Xin; Qian, Jiali; You, Zhiyuan; Liu, Bo; Chang, Chunmei; Zhou, Tianhua; Liu, Wei] Zhejiang Univ, Sch Med, Program Mol & Cell Biol, Dept Biochem & Mol Biol, Hangzhou 310058, Zhejiang, Peoples R China.
[Lippincott-Schwartz, Jennifer] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Metab Program, NIH, Bethesda, MD 20892 USA.
[Liu, Wei] Zhejiang Univ, Sch Med, Affiliated Hosp 1, Collaborat Innovat Ctr Diag & Treatment Infect Di, Hangzhou 310003, Zhejiang, Peoples R China.
RP Liu, W (reprint author), Zhejiang Univ, Sch Med, Program Mol & Cell Biol, Dept Biochem & Mol Biol, Hangzhou 310058, Zhejiang, Peoples R China.
EM liuwei666@zju.edu.cn
FU National Basic Research Program of China [2011CB910100, 2013CB910200];
National Natural Science Foundation of China [31171288, 31271431]
FX We are grateful to the Imaging Center of Zhejiang University School of
Medicine for their assistance in confocal microscopy and electron
microscopy. We thank Hong Liu, Tingting Song (Zhejiang University), and
Jingjing Tong (Tsinghua University) for other technical support and
members of Dr. Liu's lab for helpful discussions. This study was
supported by the National Basic Research Program of China (2011CB910100
and 2013CB910200) and National Natural Science Foundation of China
(31171288 and 31271431).
NR 41
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U1 4
U2 26
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 1097-2765
EI 1097-4164
J9 MOL CELL
JI Mol. Cell
PD FEB 5
PY 2015
VL 57
IS 3
BP 456
EP 466
DI 10.1016/j.molcel.2014.12.013
PG 11
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA CB3TD
UT WOS:000349550700009
PM 25601754
ER
PT J
AU Do, R
Stitziel, NO
Won, HH
Jorgensen, AB
Duga, S
Merlini, PA
Kiezun, A
Farrall, M
Goel, A
Zuk, O
Guella, I
Asselta, R
Lange, LA
Peloso, GM
Auer, PL
Girelli, D
Martinelli, N
Farlow, DN
DePristo, MA
Roberts, R
Stewart, AFR
Saleheen, D
Danesh, J
Epstein, SE
Sivapalaratnam, S
Hovingh, GK
Kastelein, JJ
Samani, NJ
Schunkert, H
Erdmann, J
Shah, SH
Kraus, WE
Davies, R
Nikpay, M
Johansen, CT
Wang, J
Hegele, RA
Hechter, E
Marz, W
Kleber, ME
Huang, J
Johnson, AD
Li, MY
Burke, GL
Gross, M
Liu, YM
Assimes, TL
Heiss, G
Lange, EM
Folsom, AR
Taylor, HA
Olivieri, O
Hamsten, A
Clarke, R
Reilly, DF
Yin, W
Rivas, MA
Donnelly, P
Rossouw, JE
Psaty, BM
Herrington, DM
Wilson, JG
Rich, SS
Bamshad, MJ
Tracy, RP
Cupples, LA
Rader, DJ
Reilly, MP
Spertus, JA
Cresci, S
Hartiala, J
Tang, WHW
Hazen, SL
Allayee, H
Reiner, AP
Carlson, CS
Kooperberg, C
Jackson, RD
Boerwinkle, E
Lander, ES
Schwartz, SM
Siscovick, DS
McPherson, R
Tybjaerg-Hansen, A
Abecasis, GR
Watkins, H
Nickerson, DA
Ardissino, D
Sunyaev, SR
O'Donnell, CJ
Altshuler, D
Gabriel, S
Kathiresan, S
AF Do, Ron
Stitziel, Nathan O.
Won, Hong-Hee
Jorgensen, Anders Berg
Duga, Stefano
Merlini, Pier Angelica
Kiezun, Adam
Farrall, Martin
Goel, Anuj
Zuk, Or
Guella, Illaria
Asselta, Rosanna
Lange, Leslie A.
Peloso, Gina M.
Auer, Paul L.
Girelli, Domenico
Martinelli, Nicola
Farlow, Deborah N.
DePristo, Mark A.
Roberts, Robert
Stewart, Alexander F. R.
Saleheen, Danish
Danesh, John
Epstein, Stephen E.
Sivapalaratnam, Suthesh
Hovingh, G. Kees
Kastelein, John J.
Samani, Nilesh J.
Schunkert, Heribert
Erdmann, Jeanette
Shah, Svati H.
Kraus, William E.
Davies, Robert
Nikpay, Majid
Johansen, Christopher T.
Wang, Jian
Hegele, Robert A.
Hechter, Eliana
Marz, Winfried
Kleber, Marcus E.
Huang, Jie
Johnson, Andrew D.
Li, Mingyao
Burke, Greg L.
Gross, Myron
Liu, Yongmei
Assimes, Themistocles L.
Heiss, Gerardo
Lange, Ethan M.
Folsom, Aaron R.
Taylor, Herman A.
Olivieri, Oliviero
Hamsten, Anders
Clarke, Robert
Reilly, Dermot F.
Yin, Wu
Rivas, Manuel A.
Donnelly, Peter
Rossouw, Jacques E.
Psaty, Bruce M.
Herrington, David M.
Wilson, James G.
Rich, Stephen S.
Bamshad, Michael J.
Tracy, Russell P.
Cupples, L. Adrienne
Rader, Daniel J.
Reilly, Muredach P.
Spertus, John A.
Cresci, Sharon
Hartiala, Jaana
Tang, W. H. Wilson
Hazen, Stanley L.
Allayee, Hooman
Reiner, Alex P.
Carlson, Christopher S.
Kooperberg, Charles
Jackson, Rebecca D.
Boerwinkle, Eric
Lander, Eric S.
Schwartz, Stephen M.
Siscovick, David S.
McPherson, Ruth
Tybjaerg-Hansen, Anne
Abecasis, Goncalo R.
Watkins, Hugh
Nickerson, Deborah A.
Ardissino, Diego
Sunyaev, Shamil R.
O'Donnell, Christopher J.
Altshuler, David
Gabriel, Stacey
Kathiresan, Sekar
CA NHLBI Exome Sequencing Project
TI Exome sequencing identifies rare LDLR and APOA5 alleles conferring risk
for myocardial infarction
SO NATURE
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; CORONARY-ARTERY-DISEASE; SINGLE NUCLEOTIDE
POLYMORPHISMS; OF-FUNCTION MUTATIONS; HEART-DISEASE; RECEPTOR; VARIANTS;
HYPERCHOLESTEROLEMIA; TRIGLYCERIDES; CHOLESTEROL
AB Myocardial infarction (MI), a leading cause of death around the world, displays a complex pattern of inheritance(1,2). When MI occurs early in life, genetic inheritance is a major component to risk(1). Previously, rare mutations in low-density lipoprotein (LDL) genes have been shown to contribute to MI risk inindividual families(3-8), whereas common variants at more than 45 loci have been associated with MI risk in the population(9-15). Here we evaluate how rare mutations contribute to early-onset MI risk in the population. We sequenced the protein-coding regions of 9,793 genomes from patients with MI at an early age (<= 50 years inmales and <= 60 years in females) along with MI-free controls. We identified two genes in which rare coding-sequence mutations were more frequent in MI cases versus controls at exome-wide significance. At low-density lipoprotein receptor (LDLR), carriers of rare non-synonymous mutations were at 4.2-fold increased risk for MI; carriers of null alleles at LDLR were at even higher risk (13-fold difference). Approximately 2% of early MI cases harbour a rare, damaging mutation in LDLR; this estimate is similar to one made more than 40 years ago using an analysis of total cholesterol(16). Among controls, about 1 in 217 carried an LDLR coding-sequence mutation and had plasma LDL cholesterol > 190 mg dl(-1). At apolipoprotein A-V (APOA5), carriers of rare non-synonymous mutations were at 2.2-fold increased risk for MI. When compared with non-carriers, LDLR mutation carriers had higher plasma LDL cholesterol, whereas APOA5 mutation carriers had higher plasma triglycerides. Recent evidence has connected MI risk with coding-sequence mutations at two genes functionally related to APOA5, namely lipoprotein lipase(15,17) and apolipoprotein C-III (refs 18, 19). Combined, these observations suggest that, as well as LDL cholesterol, disordered metabolism of triglyceride-rich lipoproteins contributes to MI risk.
C1 [Do, Ron; Won, Hong-Hee; Peloso, Gina M.; Altshuler, David; Kathiresan, Sekar] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Do, Ron; Won, Hong-Hee; Peloso, Gina M.; Kathiresan, Sekar] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.
[Do, Ron; Won, Hong-Hee; Peloso, Gina M.; Kathiresan, Sekar] Harvard Univ, Sch Med, Dept Med, Boston, MA 02114 USA.
[Do, Ron; Won, Hong-Hee; Kiezun, Adam; Zuk, Or; Peloso, Gina M.; Farlow, Deborah N.; DePristo, Mark A.; Hechter, Eliana; Folsom, Aaron R.; Lander, Eric S.; Sunyaev, Shamil R.; Altshuler, David; Gabriel, Stacey; Kathiresan, Sekar] Broad Inst, Cambridge Ctr 7, Program Med & Populat Genet, Cambridge, MA 02142 USA.
[Stitziel, Nathan O.; Cresci, Sharon] Washington Univ, Div Cardiovasc, Dept Med, Sch Med, St Louis, MO 63110 USA.
[Stitziel, Nathan O.] Washington Univ, Sch Med, Div Stat Genom, St Louis, MO 63110 USA.
[Jorgensen, Anders Berg; Tybjaerg-Hansen, Anne] Copenhagen Univ Hosp, Rigshosp, Mol Genet Sect, Dept Clin Biochem KB3011, DK-1165 Copenhagen, Denmark.
[Jorgensen, Anders Berg; Tybjaerg-Hansen, Anne] Univ Copenhagen, Fac Hlth Sci, DK-1165 Copenhagen, Denmark.
[Duga, Stefano; Guella, Illaria; Asselta, Rosanna] Univ Milan, Dipartimento Biotecnol Med & Med Traslaz, I-20122 Milan, Italy.
[Merlini, Pier Angelica] Osped Niguarda Ca Granda, Div Cardiol, I-20162 Milan, Italy.
[Farrall, Martin; Goel, Anuj; Watkins, Hugh] Univ Oxford, Wellcome Trust Ctr Human Genet, Dept Cardiovasc Med, Oxford OX1 2J, England.
[Lange, Leslie A.; Lange, Ethan M.] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA.
[Auer, Paul L.; Folsom, Aaron R.; Reiner, Alex P.; Carlson, Christopher S.; Kooperberg, Charles; Schwartz, Stephen M.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA.
[Girelli, Domenico; Martinelli, Nicola; Olivieri, Oliviero] Univ Verona, Dept Med, Sch Med, I-37129 Verona, Italy.
[Roberts, Robert; Stewart, Alexander F. R.] Univ Ottawa, Inst Heart, John & Jennifer Ruddy Canadian Cardiovasc Genet C, Ottawa, ON K1Y 4W7, Canada.
[Saleheen, Danish; Danesh, John] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge CB2 1TN, England.
[Epstein, Stephen E.] MedStar Hlth Res Inst, Cardiovasc Res Inst, Hyattsville, MD 20782 USA.
[Sivapalaratnam, Suthesh; Hovingh, G. Kees; Kastelein, John J.] Univ Amsterdam, Acad Med Ctr, Dept Vasc Med, NL-1105 AZ Amsterdam, Netherlands.
[Samani, Nilesh J.] Univ Leicester, Dept Cardiovasc Sci, Leicester LE3 9QP, Leics, England.
[Samani, Nilesh J.] Glenfield Gen Hosp, Leicester NIHR Biomed Res Unit Cardiovasc Dis, Leicester LE3 9QP, Leics, England.
[Schunkert, Heribert] Tech Univ Munich, DZHK German Res Ctr Cardiovasc Res, Munich Heart Alliance, Deutsch Herzzentrum Munchen, D-13347 Berlin, Germany.
[Erdmann, Jeanette] Med Univ Lubeck, Med Klin 2, D-23562 Lubeck, Germany.
[Shah, Svati H.] Duke Univ, Ctr Human Genet, Durham, NC 27708 USA.
[Shah, Svati H.; Kraus, William E.] Duke Univ, Sch Med, Dept Cardiol, Durham, NC 27708 USA.
[Shah, Svati H.; Kraus, William E.] Duke Univ, Sch Med, Ctr Genom Med, Durham, NC 27708 USA.
[Davies, Robert; Nikpay, Majid; McPherson, Ruth] Univ Ottawa, Inst Heart, Div Cardiol, Ottawa, ON K1Y 4W7, Canada.
[Johansen, Christopher T.; Wang, Jian; Hegele, Robert A.] Univ Western Ontario, Dept Biochem, Schulich Sch Med & Dent, Robarts Res Inst, London, ON N6A 3K7, Canada.
[Hegele, Robert A.] Univ Western Ontario, Dept Med, Schulich Sch Med & Dent, Robarts Res Inst, London, ON N6A 3K7, Canada.
[Marz, Winfried; Kleber, Marcus E.] Heidelberg Univ, Med Fac Mannheim, Mannheim Inst Publ Hlth Social & Prevent Med, D-68167 Mannheim, Germany.
[Marz, Winfried] Med Univ Graz, Clin Inst Med & Chem Lab Diagnost, A-8036 Graz, Austria.
[Marz, Winfried] Synlab Acad, D-68259 Mannheim, Germany.
[Huang, Jie; O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA.
[Johnson, Andrew D.] NHLBI, Ctr Populat Studies, Framingham Heart Study, Framingham, MA 01702 USA.
[Li, Mingyao] Univ Penn, Dept Biostat & Epidemiol, Sch Med, Philadelphia, PA 19104 USA.
[Burke, Greg L.] Univ Alabama Birmingham, Dept Epidemiol, Birmingham, AL 35233 USA.
[Gross, Myron] Univ Minnesota, Sch Med, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA.
[Liu, Yongmei] Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC 27106 USA.
[Assimes, Themistocles L.] Stanford Univ, Sch Med, Dept Med, Stanford, CA 94305 USA.
[Heiss, Gerardo] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27599 USA.
[Lange, Ethan M.] Univ N Carolina, Carolina Ctr Genome Sci, Chapel Hill, NC 27599 USA.
[Folsom, Aaron R.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN 55455 USA.
[Taylor, Herman A.] Univ Mississippi, Med Ctr, Jackson, MS 39216 USA.
[Hamsten, Anders] Karolinska Inst, Dept Med, Atherosclerosis Res Unit, S-17177 Stockholm, Sweden.
[Hamsten, Anders] Karolinska Inst, Ctr Mol Med, S-17177 Stockholm, Sweden.
[Clarke, Robert] Univ Oxford, Clin Trial Serv Unit, Oxford OX1 2JD, England.
[Clarke, Robert] Univ Oxford, Epidemiol Studies Unit, Oxford OX1 2JD, England.
[Reilly, Dermot F.; Yin, Wu] Merck Sharp & Dohme Corp, Rahway, NJ 08889 USA.
[Rivas, Manuel A.; Donnelly, Peter; Watkins, Hugh] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX1 2JD, England.
[Donnelly, Peter] Univ Oxford, Dept Stat, Oxford OX1 2JD, England.
[Rossouw, Jacques E.] NHLBI, Bethesda, MD 20824 USA.
[Psaty, Bruce M.] Univ Washington, Cardiovasc Hlth Res Unit, Dept Med, Seattle, WA 98195 USA.
[Psaty, Bruce M.] Univ Washington, Cardiovasc Hlth Res Unit, Dept Epidemiol, Seattle, WA 98195 USA.
[Psaty, Bruce M.] Univ Washington, Cardiovasc Hlth Res Unit, Dept Hlth Serv, Seattle, WA 98195 USA.
[Psaty, Bruce M.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA 98101 USA.
[Herrington, David M.] Wake Forest Sch Med, Sect Cardiol & Publ Hlth Sci, Winston Salem, NC 27106 USA.
[Wilson, James G.] Jackson State Univ, Med Ctr, Univ Mississippi, Jackson Heart Study, Jackson, MS 39217 USA.
[Rich, Stephen S.] Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA 22904 USA.
[Bamshad, Michael J.] Univ Washington, Dept Pediat, Div Med Genet, Seattle, WA 98195 USA.
[Bamshad, Michael J.] Seattle Childrens Hosp, Seattle, WA 98105 USA.
[Bamshad, Michael J.; Nickerson, Deborah A.] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA.
[Tracy, Russell P.] Univ Vermont, Dept Biochem, Burlington, VT 05405 USA.
[Cupples, L. Adrienne] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA.
[Rader, Daniel J.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Reilly, Muredach P.] Univ Penn, Perelman Sch Med, Cardiovasc Inst, Philadelphia, PA 19104 USA.
[Spertus, John A.] Univ Missouri, St Lukes Mid Amer Heart Inst, Kansas City, MO 64111 USA.
[Cresci, Sharon] Washington Univ, Dept Genet, St Louis, MO 63130 USA.
[Hartiala, Jaana; Allayee, Hooman] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA.
[Hartiala, Jaana; Allayee, Hooman] Univ So Calif, Keck Sch Med, Inst Med Genet, Los Angeles, CA 90033 USA.
[Tang, W. H. Wilson; Hazen, Stanley L.] Cleveland Clin, Cleveland, OH 44195 USA.
[Reiner, Alex P.; Schwartz, Stephen M.; Siscovick, David S.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Jackson, Rebecca D.] Ohio State Univ, Columbus, OH 43210 USA.
[Boerwinkle, Eric] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Houston, TX 77030 USA.
[Siscovick, David S.] Univ Washington, Sch Med, Dept Med, Seattle, WA 98195 USA.
[Tybjaerg-Hansen, Anne] Univ Copenhagen, Fac Hlth & Med Sci, DK-2200 Copenhagen N, Denmark.
[Abecasis, Goncalo R.] Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MO 48109 USA.
[Ardissino, Diego] Parma Hosp, Dept Cardiol, I-43100 Parma, Italy.
[Sunyaev, Shamil R.] Harvard Univ, Sch Med, Brigham & Womens Hosp, Div Genet, Boston, MA 02115 USA.
RP Kathiresan, S (reprint author), Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
EM skathiresan@partners.org
RI Singleton, Andrew/C-3010-2009; Hardy, John/C-2451-2009; de Bakker,
Paul/B-8730-2009; Hegele, Robert/G-3301-2011; Martinelli,
Nicola/J-5622-2016; Johnson, Andrew/G-6520-2013; Erdmann,
Jeanette/P-7513-2014;
OI Turner, Emily/0000-0001-9040-9229; de Bakker, Paul/0000-0001-7735-7858;
Martinelli, Nicola/0000-0001-6465-5119; Erdmann,
Jeanette/0000-0002-4486-6231; Stewart, Alexandre/0000-0003-2673-9164;
Asselta, Rosanna/0000-0001-5351-0619; Seshadri,
Sudha/0000-0001-6135-2622; Stitziel, Nathan/0000-0002-4963-8211; Duga,
Stefano/0000-0003-3457-1410; Watkins, Hugh/0000-0002-5287-9016; Assimes,
Themistocles/0000-0003-2349-0009; Kleber, Marcus/0000-0003-0663-7275
FU National Heart, Lung, and Blood Institute (NHLBI); National Human Genome
Research Institute (NHGRI) of the US National Institutes of Health
(NIH); NHLBI [RC2 HL-103010, RC2 HL-102923, RC2 HL-102924, RC2
HL-102925, RC2 HL-102926, T32HL007604, T32HL007208]; NHGRI
[5U54HG003067-11]; NIH [P01 HL076491, P01 HL098055]; Massachusetts
General Hospital (MGH); Howard Goodman Fellowship from MGH; Donovan
Family Foundation [R01HL107816]; Fondation Leducq; Canadian Institutes
of Health Research; NIH/NHLBI [K08HL114642]; Foundation for
Barnes-Jewish Hospital; [RFPS-2007-3-644382]
FX The authors wish to acknowledge the support of the National Heart, Lung,
and Blood Institute (NHLBI) and the National Human Genome Research
Institute (NHGRI) of the US National Institutes of Health (NIH) and the
contributions of the research institutions, study investigators, field
staff and study participants in creating this resource for biomedical
research. Funding for the exome sequencing project (ESP) was provided by
NHLBI grants RC2 HL-103010 (HeartGO), RC2 HL-102923 (LungGO) and RC2
HL-102924 (WHISP). Exome sequencing was performed through NHLBI grants
RC2 HL-102925 (BroadGO) and RC2 HL-102926 (SeattleGO). Exome sequencing
in the ATVB, PROCARDIS, and Ottawa studies was supported by NHGRI
5U54HG003067-11 to E.S.L. and S.G. Cleveland Clinic GeneBank was
supported by NIH grants P01 HL076491 and P01 HL098055. S.K. is supported
by a Research Scholar award from the Massachusetts General Hospital
(MGH), the Howard Goodman Fellowship from MGH, the Donovan Family
Foundation, R01HL107816, and a grant from Fondation Leducq. R.D. is
supported by a Banting Fellowship from the Canadian Institutes of Health
Research. N.O.S. is supported, in part, by a career development award
from the NIH/NHLBI K08HL114642 and by The Foundation for Barnes-Jewish
Hospital. N.O.S. was supported by award number T32HL007604 from the
NHLBI. G.M.P was supported by award number T32HL007208 from the NHLBI.
The content is solely the responsibility of the authors and does not
necessarily represent the official views of the NHLBI, NHGRI, or NIH.
The Italian ATVB Study was supported by a grant from RFPS-2007-3-644382.
A full listing of acknowledgements is provided in the Supplementary
Information.
NR 48
TC 90
Z9 91
U1 6
U2 42
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 FEB 5
PY 2015
VL 518
IS 7537
BP 102
EP +
DI 10.1038/nature13917
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CA7LE
UT WOS:000349098000040
PM 25487149
ER
PT J
AU Marrazzo, JM
Ramjee, G
Richardson, BA
Gomez, K
Mgodi, N
Nair, G
Palanee, T
Nakabiito, C
van der Straten, A
Noguchi, L
Hendrix, CW
Dai, JY
Ganesh, S
Mkhize, B
Taljaard, M
Parikh, UM
Piper, J
Masse, B
Grossman, C
Rooney, J
Schwartz, JL
Watts, H
Marzinke, MA
Hillier, SL
McGowan, IM
Chirenje, ZM
AF Marrazzo, Jeanne M.
Ramjee, Gita
Richardson, Barbra A.
Gomez, Kailazarid
Mgodi, Nyaradzo
Nair, Gonasagrie
Palanee, Thesla
Nakabiito, Clemensia
van der Straten, Ariane
Noguchi, Lisa
Hendrix, Craig W.
Dai, James Y.
Ganesh, Shayhana
Mkhize, Baningi
Taljaard, Marthinette
Parikh, Urvi M.
Piper, Jeanna
Masse, Benoit
Grossman, Cynthia
Rooney, James
Schwartz, Jill L.
Watts, Heather
Marzinke, Mark A.
Hillier, Sharon L.
McGowan, Ian M.
Chirenje, Z. Mike
CA VOICE Study Team
TI Tenofovir-Based Preexposure Prophylaxis for HIV Infection among African
Women
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID ANTIRETROVIRAL PROPHYLAXIS; PREVENTION; TRIALS; TRANSMISSION;
MICROBICIDE; ADHERENCE; GEL
AB BACKGROUND
Reproductive-age women need effective interventions to prevent the acquisition of human immunodeficiency virus type 1 (HIV-1) infection.
METHODS
We conducted a randomized, placebo-controlled trial to assess daily treatment with oral tenofovir disoproxil fumarate (TDF), oral tenofovir-emtricitabine (TDF-FTC), or 1% tenofovir (TFV) vaginal gel as preexposure prophylaxis against HIV-1 infection in women in South Africa, Uganda, and Zimbabwe. HIV-1 testing was performed monthly, and plasma TFV levels were assessed quarterly.
RESULTS
Of 12,320 women who were screened, 5029 were enrolled in the study. The rate of retention in the study was 91% during 5509 person-years of follow-up. A total of 312 HIV-1 infections occurred; the incidence of HIV-1 infection was 5.7 per 100 personyears. In the modified intention-to-treat analysis, the effectiveness was -49.0% with TDF (hazard ratio for infection, 1.49; 95% confidence interval [CI], 0.97 to 2.29), -4.4% with TDF-FTC (hazard ratio, 1.04; 95% CI, 0.73 to 1.49), and 14.5% with TFV gel (hazard ratio, 0.85; 95% CI, 0.61 to 1.21). In a random sample, TFV was detected in 30%, 29%, and 25% of available plasma samples from participants randomly assigned to receive TDF, TDF-FTC, and TFV gel, respectively. Independent predictors of TFV detection included being married, being older than 25 years of age, and being multiparous. Detection of TFV in plasma was negatively associated with characteristics predictive of HIV-1 acquisition. Elevations of serum creatinine levels were seen more frequently among participants randomly assigned to receive oral TDF-FTC than among those assigned to receive oral placebo (1.3% vs. 0.2%, P = 0.004). We observed no significant differences in the frequencies of other adverse events.
CONCLUSIONS
None of the drug regimens we evaluated reduced the rates of HIV-1 acquisition in an intention-to-treat analysis. Adherence to study drugs was low.
C1 [Marrazzo, Jeanne M.] Univ Washington, Seattle, WA 98104 USA.
[Richardson, Barbra A.; Dai, James Y.; Masse, Benoit] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, Seattle, WA 98104 USA.
[Ramjee, Gita; Ganesh, Shayhana] MRC, HIV Prevent Res Unit, Durban, South Africa.
[Nair, Gonasagrie] Ctr AIDS Programme Res South Africa CAPRISA, Durban, South Africa.
[Palanee, Thesla] Witwatersrand Reprod Hlth & HIV Res Inst, Johannesburg, South Africa.
[Mkhize, Baningi] Perinatal HIV Res Unit, Johannesburg, South Africa.
[Taljaard, Marthinette] AURUM Inst, Klerksdorp, South Africa.
[Gomez, Kailazarid] FHI 360, Durham, NC USA.
[Mgodi, Nyaradzo; Chirenje, Z. Mike] Univ Zimbabwe Univ Calif San Francisco Res Progra, Harare, Zimbabwe.
[Nakabiito, Clemensia] Makerere Univ Johns Hopkins Univ Res Collaborat, Kampala, Uganda.
[van der Straten, Ariane] Res Triangle Inst RTI Int, Womens Global Hlth Imperat, San Francisco, CA USA.
[Noguchi, Lisa; Parikh, Urvi M.; Hillier, Sharon L.; McGowan, Ian M.] Univ Pittsburgh, Med Ctr, Magee Womens Res Inst, Pittsburgh, PA USA.
[Hendrix, Craig W.; Marzinke, Mark A.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
[Piper, Jeanna] NIAID, Div Aids, NIH, Bethesda, MD 20892 USA.
[Grossman, Cynthia] NIMH, NIH, Bethesda, MD 20892 USA.
[Watts, Heather] Eunice Shriver Kennedy Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
[Rooney, James] Gilead Sci Inc, Foster City, CA 94404 USA.
[Schwartz, Jill L.] CONRAD, Arlington, VA USA.
[Masse, Benoit] Univ Montreal, Ctr Hosp Univ St Justine, Montreal, PQ, Canada.
RP Marrazzo, JM (reprint author), Univ Washington, Harborview Med Ctr, Div Infect Dis, 325 9th Ave,Mailbox 359932, Seattle, WA 98104 USA.
EM jmm2@uw.edu
OI Masse, Benoit/0000-0002-4944-8098; Cranston, Ross/0000-0002-2687-6217;
Marrazzo, Jeanne/0000-0002-9277-7364
FU Gilead Sciences
FX Dr. Hendrix reports receiving grant support from Gilead Sciences, and
Dr. Rooney, being an employee of and holding stock options in Gilead
Sciences. Dr. Rooney also reports pending patents related to the use of
tenofovir for prevention of genital herpes simplex virus infection (US
13/700,710 and WO 2011/156416).
NR 19
TC 241
Z9 248
U1 4
U2 28
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
EI 1533-4406
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD FEB 5
PY 2015
VL 372
IS 6
BP 509
EP 518
DI 10.1056/NEJMoa1402269
PG 10
WC Medicine, General & Internal
SC General & Internal Medicine
GA CA8CH
UT WOS:000349143600005
PM 25651245
ER
PT J
AU Saver, JL
Starkman, S
Eckstein, M
Stratton, SJ
Pratt, FD
Hamilton, S
Conwit, R
Liebeskind, DS
Sung, G
Kramer, I
Moreau, G
Goldweber, R
Sanossian, N
AF Saver, Jeffrey L.
Starkman, Sidney
Eckstein, Marc
Stratton, Samuel J.
Pratt, Franklin D.
Hamilton, Scott
Conwit, Robin
Liebeskind, David S.
Sung, Gene
Kramer, Ian
Moreau, Gary
Goldweber, Robert
Sanossian, Nerses
CA FAST-MAG Investigators Coordinator
TI Prehospital Use of Magnesium Sulfate as Neuroprotection in Acute Stroke
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Article
ID ACUTE ISCHEMIC-STROKE; HEALTH-CARE PROFESSIONALS; TRIAL; THERAPY; FIELD;
ASSOCIATION; METHODOLOGY; GUIDELINES; MANAGEMENT
AB Background
Magnesium sulfate is neuroprotective in preclinical models of stroke and has shown signals of potential efficacy with an acceptable safety profile when delivered early after stroke onset in humans. Delayed initiation of neuroprotective agents has hindered earlier phase 3 trials of neuroprotective agents.
Methods
We randomly assigned patients with suspected stroke to receive either intravenous magnesium sulfate or placebo, beginning within 2 hours after symptom onset. A loading dose was initiated by paramedics before the patient arrived at the hospital, and a 24-hour maintenance infusion was started on the patient's arrival at the hospital. The primary outcome was the degree of disability at 90 days, as measured by scores on the modified Rankin scale (range, 0 to 6, with higher scores indicating greater disability).
Results
Among the 1700 enrolled patients (857 in the magnesium group and 843 in the placebo group), the mean (+/- SD) age was 69 +/- 13 years, 42.6% were women, and the mean pretreatment score on the Los Angeles Motor Scale of stroke severity (range, 0 to 10, with higher scores indicating greater motor deficits) was 3.7 +/- 1.3. The final diagnosis of the qualifying event was cerebral ischemia in 73.3% of patients, intracranial hemorrhage in 22.8%, and a stroke-mimicking condition in 3.9%. The median interval between the time the patient was last known to be free of stroke symptoms and the start of the study-drug infusion was 45 minutes (interquartile range, 35 to 62), and 74.3% of patients received the study-drug infusion within the first hour after symptom onset. There was no significant shift in the distribution of 90-day disability outcomes on the global modified Rankin scale between patients in the magnesium group and those in the placebo group (P = 0.28 by the Cochran-Mantel-Haenszel test); mean scores at 90 days did not differ between the magnesium group and the placebo group (2.7 in each group, P = 1.00). No significant between-group differences were noted with respect to mortality (15.4% in the magnesium group and 15.5% in the placebo group, P = 0.95) or all serious adverse events.
Conclusions
Prehospital initiation of magnesium sulfate therapy was safe and allowed the start of therapy within 2 hours after the onset of stroke symptoms, but it did not improve disability outcomes at 90 days.
C1 [Saver, Jeffrey L.; Starkman, Sidney; Liebeskind, David S.] Univ Calif Los Angeles, David Geffen Sch Med, Comprehens Stroke Ctr, Los Angeles, CA 90095 USA.
[Saver, Jeffrey L.; Starkman, Sidney; Liebeskind, David S.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA.
[Starkman, Sidney; Pratt, Franklin D.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Emergency Med, Los Angeles, CA 90095 USA.
[Eckstein, Marc] Univ So Calif, Keck Sch Med, Dept Emergency Med, Los Angeles, CA 90033 USA.
[Sung, Gene; Sanossian, Nerses] Univ So Calif, Keck Sch Med, Dept Neurol, Los Angeles, CA 90033 USA.
[Eckstein, Marc] Presbyterian Intercommun Hosp, Los Angeles Fire Dept, Los Angeles, CA USA.
[Pratt, Franklin D.] Presbyterian Intercommun Hosp, Los Angeles Cty Fire Dept, Los Angeles, CA USA.
[Kramer, Ian] Presbyterian Intercommun Hosp, Dept Emergency Med, Los Angeles, CA USA.
[Moreau, Gary] Huntington Mem Hosp, Long Beach Mem Med Ctr, Dept Emergency Med, Los Angeles, CA USA.
[Goldweber, Robert] Huntington Mem Hosp, Dept Emergency Med, Dept Emergency Med, Los Angeles, CA USA.
[Stratton, Samuel J.] Los Angeles Cty Emergency Med Serv EMS Agcy, Torrance, CA USA.
[Stratton, Samuel J.] Harbor UCLA Med Ctr, Dept Emergency Med, Torrance, CA 90509 USA.
[Hamilton, Scott] Stanford Univ, Palo Alto, CA 94304 USA.
[Conwit, Robin] Natl Inst Neurol Disorders & Stroke, Bethesda, MD USA.
RP Saver, JL (reprint author), Univ Calif Los Angeles, Comprehens Stroke Ctr, 710 Westwood Plaza, Los Angeles, CA 90095 USA.
EM jsaver@mednet.ucla.edu
OI Saver, Jeffrey/0000-0001-9141-2251
FU National Institute of Neurological Disorders and Stroke
FX Supported by the National Institute of Neurological Disorders and
Stroke.
NR 24
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U1 0
U2 14
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
EI 1533-4406
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD FEB 5
PY 2015
VL 372
IS 6
BP 528
EP 536
DI 10.1056/NEJMoa1408827
PG 9
WC Medicine, General & Internal
SC General & Internal Medicine
GA CA8CH
UT WOS:000349143600007
PM 25651247
ER
PT J
AU Sandino, CM
Kellman, P
Arai, AE
Hansen, MS
Xue, H
AF Sandino, Christopher M.
Kellman, Peter
Arai, Andrew E.
Hansen, Michael S.
Xue, Hui
TI Myocardial T2*mapping: influence of noise on accuracy and precision
SO JOURNAL OF CARDIOVASCULAR MAGNETIC RESONANCE
LA English
DT Article
DE T2*mapping; Iron overload; Mapping; Hemochromatosis; Thalassemia
ID T2-ASTERISK-CARDIOVASCULAR MAGNETIC-RESONANCE; SICKLE-CELL-DISEASE; IRON
OVERLOAD; WATER/FAT SEPARATION; IMAGE-RECONSTRUCTION; THALASSEMIA;
HEART; DIAGNOSIS
AB Background: Pixel-wise, parametric T2* mapping is emerging as a means of automatic measurement of iron content in tissues. It enables quick, intuitive interpretation and provides the potential benefit of spatial context between tissues. However, pixel-wise mapping uses much lower SNR data to estimate T2* when compared to region-based mapping thereby decreasing both its accuracy and precision. In this study, the effects that noise has on the precision and accuracy of pixel-wise T2* mapping were investigated and techniques to mitigate those effects are proposed.
Methods: To study precision across T2* mapping techniques, a pipeline to estimate the pixel-wise standard deviation (SD) of the T2* based on the fit residuals is proposed. For validation, a Monte-Carlo analysis was performed in which T2* phantoms were scanned N = 64 times, the true SD was measured and compared to the estimated SD. To improve accuracy and precision, the automatic truncation method for mitigating noise bias was extended to pixel-wise fitting by using an SNR scaled image reconstruction and truncating low SNR measurements. Finally, the precision and accuracy of non-linear regression with and without automatic truncation, were investigated using Monte-Carlo simulations.
Results: Measured and estimated SD's were >99.9% correlated for non-linear regression with and without truncation. Non-linear regression with automatic truncation was shown to be the best mapping technique for improving accuracy and precision in low T2* and low SNR measurements.
Conclusions: A method for applying an automatic truncation method to pixel-wise T2* mapping that reduces T2* overestimation due to noise bias was proposed. A formulation for estimating pixel-wise standard deviation (SD) maps for T2* that can serve as a quality map for interpreting images and for comparison of imaging protocols was also proposed and validated.
C1 [Sandino, Christopher M.; Kellman, Peter; Arai, Andrew E.; Hansen, Michael S.; Xue, Hui] NHLBI, NIH, DHHS, Bethesda, MD 20892 USA.
[Sandino, Christopher M.] Univ So Calif, Dept Elect Engn, Los Angeles, CA 90089 USA.
RP Xue, H (reprint author), NHLBI, NIH, DHHS, 10 Ctr Dr MSC 1061, Bethesda, MD 20892 USA.
EM hui.xue@nih.gov
RI Hansen, Michael/J-5391-2015
OI Hansen, Michael/0000-0002-8087-8731
FU National Heart, Lung and Blood Institute, National Institutes of Health
by the Division of Intramural Research, NHLBI, NIH, DHHS
[HL004607-14CPB]
FX Supported by the National Heart, Lung and Blood Institute, National
Institutes of Health by the Division of Intramural Research, NHLBI, NIH,
DHHS (HL004607-14CPB).
NR 25
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Z9 4
U1 0
U2 1
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 FEB 4
PY 2015
VL 17
AR 7
DI 10.1186/s12968-015-0115-3
PG 9
WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical
Imaging
SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine &
Medical Imaging
GA CB9IM
UT WOS:000349945200001
PM 25648167
ER
PT J
AU Kupferschmidt, DA
Cody, PA
Lovinger, DM
Davis, MI
AF Kupferschmidt, David A.
Cody, Patrick A.
Lovinger, David M.
Davis, Margaret I.
TI Brain BLAQ: Post-hoc thick-section histochemistry for localizing
optogenetic constructs in neurons and their distal terminals
SO FRONTIERS IN NEUROANATOMY
LA English
DT Article
DE histochemistry; optogenetic neuroimaging; striosome and matrix
compartments; tract-tracing; viral expression; Cre transgenic mouse
ID SODIUM-BOROHYDRIDE; NUCLEUS-ACCUMBENS; CATECHOL AMINES; MOUSE-BRAIN;
FLUORESCENCE; AUTOFLUORESCENCE; RECONSTRUCTION; RESOLUTION; REDUCTION;
SYSTEMS
AB Optogenetic constructs have revolutionized modern neuroscience, but the ability to accurately and efficiently assess their expression in the brain and associate it with prior functional measures remains a challenge. High-resolution imaging of thick, fixed brain sections would make such post-hoc assessment and association possible; however, thick sections often display autofluorescence that limits their compatibility with fluorescence microscopy. We describe and evaluate a method we call "Brain BLAQ" (Block Lipids and Aldehyde Quench) to rapidly reduce autofluorescence in thick brain sections, enabling efficient axon-level imaging of neurons and their processes in conventional tissue preparations using standard epifluorescence microscopy. Following viral-mediated transduction of optogenetic constructs and fluorescent proteins in mouse cortical pyramidal and dopaminergic neurons, we used BLAQ to assess innervation patterns in the striatum, a region in which autofluorescence often obscures the imaging of fine neural processes. After BLAQ treatment of 250350 mu m-thick brain sections, axons and puncta of labeled afferents were visible throughout the striatum using a standard epifluorescence stereomicroscope. BLAQ histochemistry confirmed that motor cortex (M1) projections preferentially innervated the matrix component of lateral striatum, whereas medial prefrontal cortex projections terminated largely in dorsal striosomes and distinct nucleus accumbens subregions. Ventral tegmental area dopaminergic projections terminated in a similarly heterogeneous pattern within nucleus accumbens and ventral striatum. Using a minimal number of easily manipulated and visualized sections, and microscopes available in most neuroscience laboratories, BLAQ enables simple, high-resolution assessment of virally transduced optogenetic construct expression, and post-hoc association of this expression with molecular markers, physiology and behavior.
C1 [Kupferschmidt, David A.; Cody, Patrick A.; Lovinger, David M.; Davis, Margaret I.] NIAAA, Sect Synapt Pharmacol & In Vivo Neural Funct, Lab Integrat Neurosci, NIH, Bethesda, MD 20892 USA.
RP Davis, MI (reprint author), NIAAA, Sect Synapt Pharmacol & In Vivo Neural Funct, Lab Integrat Neurosci, NIH, 5625 Fishers Lane,TS 20,MSC9411, Bethesda, MD 20892 USA.
EM midavis@mail.nih.gov
OI Davis, Margaret/0000-0002-0489-8351
FU National Institute of Alcohol Abuse and Alcoholism Division of
Intramural Clinical and Biological Research
FX The authors thank Dr. William Shain for excellent training, years of
useful discussions on thick-section imaging techniques, and comments
during the preparation of this manuscript. We also thank Dr. Shain and
Kristen Trett for testing the utility of BLAQ for high-resolution
automated confocal imaging, and Amber Luo for assistance with mice
genotyping. The Iba antibody was generously provided by Dr. Giorgi
Kharebava, Laboratory of Molecular Signaling, NIAAA. This work was
supported by the National Institute of Alcohol Abuse and Alcoholism
Division of Intramural Clinical and Biological Research and is subject
to the NIH Public Access Policy. The authors declare no competing
financial interests.
NR 33
TC 1
Z9 1
U1 0
U2 5
PU FRONTIERS RESEARCH FOUNDATION
PI LAUSANNE
PA PO BOX 110, LAUSANNE, 1015, SWITZERLAND
SN 1662-5129
J9 FRONT NEUROANAT
JI Front. Neuroanat.
PD FEB 4
PY 2015
VL 9
AR 6
DI 10.3389/fnana.2015.00006
PG 9
WC Anatomy & Morphology; Neurosciences
SC Anatomy & Morphology; Neurosciences & Neurology
GA CB6QL
UT WOS:000349751500001
PM 25698938
ER
PT J
AU Huang, Y
Karuna, ST
Janes, H
Frahm, N
Nason, M
Edlefsen, PT
Kublin, JG
Corey, L
McElrath, MJ
Gilbert, PB
AF Huang, Yunda
Karuna, Shelly T.
Janes, Holly
Frahm, Nicole
Nason, Martha
Edlefsen, Paul T.
Kublin, James G.
Corey, Lawrence
McElrath, M. Juliana
Gilbert, Peter B.
TI Use of placebos in Phase 1 preventive HIV vaccine clinical trials
SO VACCINE
LA English
DT Article
DE Randomization; Blinding; Sample sizes; Clinical trial; Vaccine safety;
Vaccine tolerability; Vaccine immunogenicity
ID SAFETY; PRIME
AB Phase 1 preventive HIV vaccine trials are often designed as randomized, double-blind studies with the inclusion of placebo recipients. Careful consideration is needed to determine when the inclusion of placebo recipients is highly advantageous and when it is optional for achieving the study objectives of assessing vaccine safety, tolerability and immunogenicity. The inclusion of placebo recipients is generally important to form a reference group that ensures fair evaluation and interpretation of subjective study endpoints, or endpoints whose levels may change due to exposures besides vaccination. In some settings, however, placebo recipients are less important because other data sources and tools are available to achieve the study objectives. (C) 2014 Elsevier Ltd. All rights reserved.
C1 [Huang, Yunda; Karuna, Shelly T.; Janes, Holly; Frahm, Nicole; Edlefsen, Paul T.; Kublin, James G.; Corey, Lawrence; McElrath, M. Juliana; Gilbert, Peter B.] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, Seattle, WA 98109 USA.
[Huang, Yunda; Janes, Holly; Edlefsen, Paul T.; Gilbert, Peter B.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA.
[Janes, Holly; Edlefsen, Paul T.; Gilbert, Peter B.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Frahm, Nicole; McElrath, M. Juliana] Univ Washington, Dept Global Hlth, Seattle, WA 98195 USA.
[Nason, Martha] NIAID, Div Clin Res, NIH, Bethesda, MD 20892 USA.
[Corey, Lawrence; McElrath, M. Juliana] Univ Washington, Dept Lab Med, Seattle, WA 98195 USA.
[Corey, Lawrence; McElrath, M. Juliana] Univ Washington, Dept Med, Seattle, WA USA.
RP Huang, Y (reprint author), Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Vaccine & Infect Dis Div, 1100 Fairview Ave North,M2-C202,POB 19024, Seattle, WA 98109 USA.
EM yunda@scharp.org
FU National Institute of Allergy and Infectious Diseases of the National
Institutes of Health [UM1AI068635, 2 UM1 AIO68614, UM1AI068618]
FX This work was supported by the National Institute of Allergy and
Infectious Diseases of the National Institutes of Health [UM1AI068635, 2
UM1 AIO68614 and UM1AI068618]. The content is solely the responsibility
of the authors and does not necessarily represent the official views of
the National Institutes of Health.
NR 13
TC 1
Z9 1
U1 0
U2 1
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 FEB 4
PY 2015
VL 33
IS 6
BP 749
EP 752
DI 10.1016/j.vaccine.2014.10.017
PG 4
WC Immunology; Medicine, Research & Experimental
SC Immunology; Research & Experimental Medicine
GA CB4CP
UT WOS:000349576100001
PM 25454855
ER
PT J
AU Mejias-Aponte, CA
Ye, CQ
Bonci, A
Kiyatkin, EA
Morales, M
AF Mejias-Aponte, Carlos A.
Ye, Changquan
Bonci, Antonello
Kiyatkin, Eugene A.
Morales, Marisela
TI A Subpopulation of Neurochemically-Identified Ventral Tegmental Area
Dopamine Neurons Is Excited by Intravenous Cocaine
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE cocaine; in-vivo electrophysiology; intravenous; juxtacellular; single
unit; ventral tegmental area
ID PREFRONTAL CORTEX; NUCLEUS-ACCUMBENS; IN-VIVO; GABA NEURONS; RATS;
REWARD; BURST; AMPHETAMINE; ACTIVATION; RECEPTORS
AB Systemic administration of cocaine is thought to decrease the firing rates of ventral tegmental area (VTA) dopamine (DA) neurons. However, this view is based on categorizations of recorded neurons as DA neurons using preselected electrophysiological characteristics lacking neurochemical confirmation. Without applying cellular preselection, we recorded the impulse activity of VTA neurons in response to cocaine administration in anesthetized adult rats. The phenotype of recorded neurons was determined by their juxtacellular labeling and immunohistochemical detection of tyrosine hydroxylase (TH), a DA marker. We found that intravenous cocaine altered firing rates in the majority of recorded VTA neurons. Within the cocaine-responsive neurons, half of the population was excited and the other half was inhibited. Both populations had similar discharge rates and firing regularities, and most neurons did not exhibit changes in burst firing. Inhibited neurons were more abundant in the posterior VTA, whereas excited neurons were distributed evenly throughout the VTA. Cocaine-excited neurons were more likely to be excited by footshock. Within the subpopulation of TH-positive neurons, 36% were excited by cocaine and 64% were inhibited. Within the subpopulation of TH-negative neurons, 44% were excited and 28% were inhibited. Contrary to the prevailing view that all DA neurons are inhibited by cocaine, we found a subset of confirmed VTA DA neurons that is excited by systemic administration of cocaine. We provide evidence indicating that DA neurons are heterogeneous in their response to cocaine and that VTA non-DA neurons play an active role in processing systemic cocaine.
C1 [Mejias-Aponte, Carlos A.; Ye, Changquan; Morales, Marisela] NIDA, Integrat Neurosci Res Branch, Neuronal Networks Sect, Baltimore, MD 21224 USA.
[Bonci, Antonello] NIDA, Cellular Neurobiol Res Branch, Synapt Physiol Sect, Baltimore, MD 21224 USA.
[Kiyatkin, Eugene A.] NIDA, Behav Neurosci Res Branch, Behav Neurosci Sect, Vivo Electrophysiol Unit,Intramural Res Program, Baltimore, MD 21224 USA.
[Bonci, Antonello] Johns Hopkins Univ, Sch Med, Solomon H Snyder Dept Neurosci, Baltimore, MD 21205 USA.
RP Morales, M (reprint author), NIDA, Integrat Neurosci Res Branch, Neuronal Networks Sect, Intramural Res Program,Biomed Res Ctr, Suite 200,251 Bayview Blvd, Baltimore, MD 21224 USA.
EM mmorales@nih.gov
FU National Institute on Drug Abuse Intramural Research Program
FX This work was supported by the National Institute on Drug Abuse
Intramural Research Program. We thank Robert Ator for his help in
surgeries, Jean Pieper for histology processing, and Drs. Lindsay De
Biase, Alexxai Kravitz, Jana Mejia-Tobier, Meriem Gaval Cruz, David
Barker, and David Root for their helpful comments on this manuscript.
NR 49
TC 8
Z9 8
U1 0
U2 3
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 FEB 4
PY 2015
VL 35
IS 5
BP 1965
EP 1978
DI 10.1523/JNEUROSCI.3422-13.2015
PG 14
WC Neurosciences
SC Neurosciences & Neurology
GA CB5MI
UT WOS:000349671100013
PM 25653355
ER
PT J
AU Francis, SP
Krey, JF
Krystofiak, ES
Cui, RJ
Nanda, S
Xu, WH
Kachar, B
Barr-Gillespie, PG
Shin, JB
AF Francis, Shimon P.
Krey, Jocelyn F.
Krystofiak, Evan S.
Cui, Runjia
Nanda, Sonali
Xu, Wenhao
Kachar, Bechara
Barr-Gillespie, Peter G.
Shin, Jung-Bum
TI A Short Splice Form of Xin-Actin Binding Repeat Containing 2 (XIRP2)
Lacking the Xin Repeats Is Required for Maintenance of Stereocilia
Morphology and Hearing Function
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE CRISPR; hair bundle; hair cell; hearing; stereocilia; XIRP2
ID HAIR-CELL STEREOCILIA; PROTEIN; MICE; CRISPR/CAS; DEAFNESS; BUNDLES;
RADIXIN; ALPHA; IDENTIFICATION; PROKARYOTES
AB Approximately one-third of known deafness genes encode proteins located in the hair bundle, the sensory hair cell's mechanoreceptive organelle. In previous studies, we used mass spectrometry to characterize the hair bundle's proteome, resulting in the discovery of novel bundle proteins. One such protein is Xin-actin binding repeat containing 2 (XIRP2), an actin-cross-linking protein previously reported to be specifically expressed in striated muscle. Because mutations in other actin-cross-linkers result in hearing loss, we investigated the role of XIRP2 in hearing function. In the inner ear, XIRP2 is specifically expressed in hair cells, colocalizing with actin-rich structures in bundles, the underlying cuticular plate, and the circumferential actin belt. Analysis using peptide mass spectrometry revealed that the bundle harbors a previously uncharacterized XIRP2 splice variant, suggesting XIRP2's role in the hair cell differs significantly from that reported in myocytes. To determine the role of XIRP2 in hearing, we applied clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9-mediated genome-editing technology to induce targeted mutations into the mouse Xirp2 gene, resulting in the elimination of XIRP2 protein expression in the inner ear. Functional analysis of hearing in the resulting Xirp2-null mice revealed high-frequency hearing loss, and ultrastructural scanning electron microscopy analyses of hair cells demonstrated stereocilia degeneration in these mice. We thus conclude that XIRP2 is required for long-term maintenance of hair cell stereocilia, and that its dysfunction causes hearing loss in the mouse.
C1 [Francis, Shimon P.; Nanda, Sonali; Shin, Jung-Bum] Univ Virginia, Dept Neurosci, Charlottesville, VA 22908 USA.
[Shin, Jung-Bum] Univ Virginia, Dept Brain, Charlottesville, VA 22908 USA.
[Shin, Jung-Bum] Univ Virginia, Dept Immunol, Charlottesville, VA 22908 USA.
[Shin, Jung-Bum] Univ Virginia, Glia Ctr, Charlottesville, VA 22908 USA.
[Xu, Wenhao] Univ Virginia, Gene Targeting & Transgen Facil, Charlottesville, VA 22908 USA.
[Krey, Jocelyn F.; Barr-Gillespie, Peter G.] Oregon Hlth & Sci Univ, Oregon Hearing Res Ctr, Portland, OR 97239 USA.
[Krey, Jocelyn F.; Barr-Gillespie, Peter G.] Oregon Hlth & Sci Univ, Vollum Inst, Portland, OR 97239 USA.
[Krystofiak, Evan S.; Cui, Runjia; Kachar, Bechara] NIDCD, NIH, Bethesda, MD 20892 USA.
RP Shin, JB (reprint author), Univ Virginia, Dept Neurosci, Charlottesville, VA 22908 USA.
EM js2ee@virginia.edu
FU National Institutes of Health-National Institute for Deafness and
Communication Disorders [R01 DC014254, K99/R00 DC009412, R01 DC002368,
R01 DC011034, P30 DC005983]
FX This study was funded by National Institutes of Health-National
Institute for Deafness and Communication Disorders grants R01 DC014254
and K99/R00 DC009412 to J.B.S. and R01 DC002368, R01 DC011034, and P30
DC005983 to P.G.B.-G. We thank James Pagana, Ben Thiede, and Jeff Corwin
for helping with the SEM preparations.
NR 56
TC 14
Z9 15
U1 1
U2 1
PU SOC NEUROSCIENCE
PI WASHINGTON
PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA
SN 0270-6474
J9 J NEUROSCI
JI J. Neurosci.
PD FEB 4
PY 2015
VL 35
IS 5
BP 1999
EP 2014
DI 10.1523/JNEUROSCI.3449-14.2015
PG 16
WC Neurosciences
SC Neurosciences & Neurology
GA CB5MI
UT WOS:000349671100016
PM 25653358
ER
PT J
AU Abitbol, R
Lebreton, M
Hollard, G
Richmond, BJ
Bouret, S
Pessiglione, M
AF Abitbol, Raphaelle
Lebreton, Mael
Hollard, Guillaume
Richmond, Barry J.
Bouret, Sebastien
Pessiglione, Mathias
TI Neural Mechanisms Underlying Contextual Dependency of Subjective Values:
Converging Evidence from Monkeys and Humans
SO JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE decision making; electrophysiology; fMRI; neuroeconomics; reward;
ventromedial prefrontal cortex
ID VENTROMEDIAL PREFRONTAL CORTEX; ORBITOFRONTAL CORTEX; ACTIVITY
FLUCTUATIONS; BRAIN ACTIVITY; REWARD VALUE; VALUATION SYSTEM; MACAQUE
MONKEY; FREE-ENERGY; VARIABILITY; CHOICE
AB A major challenge for decision theory is to account for the instability of expressed preferences across time and context. Such variability could arise from specific properties of the brain system used to assign subjective values. Growing evidence has identified the ventromedial prefrontal cortex (VMPFC) as a key node of the human brain valuation system. Here, we first replicate this observation with an fMRI study in humans showing that subjective values of painting pictures, as expressed in explicit pleasantness ratings, are specifically encoded in the VMPFC. We then establish a bridge with monkey electrophysiology, by comparing single-unit activity evoked by visual cues between theVMPFCand the orbitofrontal cortex. At the neural population level, expected reward magnitude was only encoded in the VMPFC, which also reflected subjective cue values, as expressed in Pavlovian appetitive responses. In addition, we demonstrate in both species that the additive effect of prestimulus activity on evoked activity has a significant impact on subjective values. In monkeys, the factor dominating prestimulus VMPFC activity was trial number, which likely indexed variations in internal dispositions related to fatigue or satiety. In humans, prestimulus VMPF Cactivity was externally manipulated through changes in the musical context, which induced a systematic bias in subjective values. Thus, the apparent stochasticity of preferences might relate to the VMPFC automatically aggregating the values of contextual features, which would bias subsequent valuation because of temporal autocorrelation in neural activity.
C1 [Abitbol, Raphaelle; Lebreton, Mael; Bouret, Sebastien; Pessiglione, Mathias] Grp Hosp Pitie Salpetriere, Inst Cerveau & Moelle Epiniere, Motivat Brain & Behav Lab, Ctr Neuroimagerie Rech, F-75013 Paris, France.
[Abitbol, Raphaelle; Hollard, Guillaume] Univ Paris 01, Ctr Econ Sorbonne, F-75013 Paris, France.
[Abitbol, Raphaelle; Lebreton, Mael; Bouret, Sebastien; Pessiglione, Mathias] UPMC P6, UMR S 1127, CNRS UMR 7225, INSERM U975, F-75651 Paris 13, France.
[Richmond, Barry J.; Bouret, Sebastien] NIMH, Lab Neuropsychol, NIH, US Dept HHS, Bethesda, MD 20892 USA.
RP Pessiglione, M (reprint author), Grp Hosp Pitie Salpetriere, Inst Cerveau & Moelle Epiniere, Brain Behav Team, F-75013 Paris, France.
EM mathias.pessiglione@gmail.com
RI Pessiglione, Mathias/E-2141-2017
FU European Research Council; National Institutes of Health Intra-Mural
Research Program; French Direction Generale de l'Armement and
Investissement d'avenir [ANR-10-IAIHU-06]
FX This work was supported by European Research Council Starting Grant
ERC-BioMotiv and National Institutes of Health Intra-Mural Research
Program. It has also benefited from the Federation pour la Recherche
Medicale. R.A. was supported by the French Direction Generale de
l'Armement and Investissement d'avenir ANR-10-IAIHU-06.
NR 44
TC 6
Z9 6
U1 0
U2 22
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 FEB 4
PY 2015
VL 35
IS 5
BP 2308
EP 2320
DI 10.1523/JNEUROSCI.1878-4.2015
PG 13
WC Neurosciences
SC Neurosciences & Neurology
GA CB5MI
UT WOS:000349671100042
PM 25653384
ER
PT J
AU Lee, JH
Li, F
Grishaev, A
Bax, A
AF Lee, Jung Ho
Li, Fang
Grishaev, Alexander
Bax, Ad
TI Quantitative Residue-Specific Protein Backbone Torsion Angle Dynamics
from Concerted Measurement of (3)J Couplings
SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
LA English
DT Article
ID NUCLEAR-MAGNETIC-RESONANCE; DIPOLAR COUPLINGS; NMR-SPECTROSCOPY;
UBIQUITIN; MOTION; RELAXATION; CONSTANTS
AB Three-bond (3)J(C'C') and (3)J(HNH alpha) couplings in peptides and proteins are functions of the intervening backbone torsion angle phi. In well-ordered regions, (3)J(HNH alpha) is tightly correlated with (3)J(C'C'), but the presence of large phi angle fluctuations differentially affects the two types of couplings. Assuming the phi angles follow a Gaussian distribution, the width of this distribution can be extracted from (3)J(C'C') and (3)J(HNH alpha), as demonstrated for the folded proteins ubiquitin and GB3. In intrinsically disordered proteins, slow transverse relaxation permits measurement of (3)J(C'C')' and (3)J(HNH) couplings at very high precision, and impact of factors other than the intervening torsion angle on (3)J will be minimal, making these couplings exceptionally valuable structural reporters. Analysis of alpha-synuclein yields rather homogeneous widths of 69 +/- 6 degrees for the phi angle distributions and (3)J(C'C') values that agree well with those of a recent maximum entropy analysis of chemical shifts, J couplings, and H-1-H-1 NOEs. Data are consistent with a modest (<= 30%) population of the polyproline II region.
C1 [Lee, Jung Ho; Li, Fang; Grishaev, Alexander; Bax, Ad] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
RP Bax, A (reprint author), NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
EM bax@nih.gov
FU Intramural Research Program of the National Institute of Diabetes and
Digestive and Kidney Diseases; Intramural Antiviral Target Program of
the Office of the Director, NIH; KVSTA Fellowship; China Scholarship
Council
FX We thank J. Ying, J. L. Baber, and A. Mantsyzov for technical support.
This work was supported by the Intramural Research Program of the
National Institute of Diabetes and Digestive and Kidney Diseases and by
the Intramural Antiviral Target Program of the Office of the Director,
NIH. J.H.L. is the recipient of the KVSTA Fellowship, and F.L.
acknowledges financial support from the China Scholarship Council.
NR 31
TC 9
Z9 9
U1 2
U2 26
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0002-7863
J9 J AM CHEM SOC
JI J. Am. Chem. Soc.
PD FEB 4
PY 2015
VL 137
IS 4
BP 1432
EP 1435
DI 10.1021/ja512593s
PG 4
WC Chemistry, Multidisciplinary
SC Chemistry
GA CA8AJ
UT WOS:000349138600013
PM 25590347
ER
PT J
AU Xu, BJM
Levy, S
Butman, J
Pham, D
Cohen, LG
Sandrini, M
AF Xu, Benjamin
Levy, Sarah
Butman, John
Pham, Dzung
Cohen, Leonardo G.
Sandrini, Marco
TI Effect of foreknowledge on neural activity of primary "go" responses
relates to response stopping and switching
SO FRONTIERS IN HUMAN NEUROSCIENCE
LA English
DT Article
DE response inhibition; foreknowledge; fMRI stop-signal; impulse
ID INHIBITORY MOTOR CONTROL; PREFRONTAL CORTEX; NEURONAL-ACTIVITY;
VISUAL-ATTENTION; SIGNAL PARADIGM; MECHANISMS; BRAIN; TASK; ACTIVATIONS;
STIMULATION
AB Being able to stop (or inhibit) an action rapidly as in a stop-signal task (SST) is an essential human ability. Previous studies showed that when a pie stimulus cue warned of the possible need to stop a response in an upcoming trial, participants' response time (RI) increased if the subsequent trial required a "go" response (i.e., "go" RI cost) relative to a trial where this uncertainty was not present. This increase of the "go" RI correlated with more efficient response stopping. However, it remains a question whether foreknowledge of upcoming inhibition trials given prior to the task is sufficient to modulate neural activity associated with the primary "go" responses irrespective of whether stopping an overt response is required. We presented three task conditions with identical primary (i.e., "go") response trials but without pre-stimulus cues. Participants were informed that Condition 1 had only "go" trials (All go condition), Condition 2 required a "stop" response for some trials (Stop condition), and Condition 3 required a response incongruent with the primary response (i.e., Switch response) for some trials (Switch condition). Participants performed the tasks during functional magnetic resonance imaging (fMRI) scans. Results showed a significant increase in the "go" RI (cost) in the Stop and Switch conditions relative to the All-go condition. The "go" RT cost was correlated with decreased inhibition time. fMRI activation in the frontal-basal-ganglia regions during the "go" responses in the Stop and Switch conditions was also correlated with the efficiency of Stop and Switch responses. These results suggest that foreknowledge prior to the task is sufficient to influence neural activity associated with the primary response and modulate inhibition efficiency, irrespective of whether stopping an overt response is required.
C1 [Xu, Benjamin; Levy, Sarah; Cohen, Leonardo G.; Sandrini, Marco] NINDS, Human Cort Physiol & Neurorehabil Sect, NIH, Bethesda, MD 20892 USA.
[Xu, Benjamin; Levy, Sarah; Pham, Dzung; Sandrini, Marco] Ctr Neurosci & Regenerat Med, Bethesda, MD USA.
[Butman, John] NIH, Ctr Clin, Dept Radiol, Bethesda, MD 20892 USA.
RP Xu, BJM (reprint author), NINDS, Human Cort Physiol & Neurorehabil Sect, NIH, 7D51 Bldg 10 Ctr Dr, Bethesda, MD 20892 USA.
EM benxu1@mail.nih.gov
RI Butman, John/J-2780-2013; Sandrini, Marco/J-2276-2014
OI Butman, John/0000-0002-1547-9195; Sandrini, Marco/0000-0002-1664-5722
FU Department of Defense through the Center for Neuroscience and
Regenerative Medicine (CNRM) [G189AN, G189BK]; Intramural Research
Program of the National Institute of Neurological Disorders and Stroke
at the National Institutes of Health
FX This research was supported, in part, by the grants (G189AN and G189BK)
from the Department of Defense through the Center for Neuroscience and
Regenerative Medicine (CNRM) and by the Intramural Research Program of
the National Institute of Neurological Disorders and Stroke at the
National Institutes of Health. We thank Leonora Wilkinson for helpful
comments.
NR 46
TC 3
Z9 3
U1 3
U2 6
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015,
SWITZERLAND
SN 1662-5161
J9 FRONT HUM NEUROSCI
JI Front. Hum. Neurosci.
PD FEB 4
PY 2015
VL 9
AR 34
DI 10.3389/fnhum.2015.00034
PG 12
WC Neurosciences; Psychology
SC Neurosciences & Neurology; Psychology
GA CA5AB
UT WOS:000348918100001
PM 25698959
ER
PT J
AU Basile, BM
AF Basile, Benjamin M.
TI Rats remind us what actually counts in episodic memory research
SO FRONTIERS IN PSYCHOLOGY
LA English
DT Editorial Material
DE episodic; semantic; source; context; rat
ID MONKEYS MACACA-MULATTA; RHESUS-MONKEYS; RECALL; HIPPOCAMPUS; METAMEMORY;
ANIMALS; BINDING; PIGEONS; EVENTS
C1 NIMH, Sect Neurobiol Learning & Memory, Lab Neuropsychol, NIH, Bethesda, MD 20892 USA.
RP Basile, BM (reprint author), NIMH, Sect Neurobiol Learning & Memory, Lab Neuropsychol, NIH, Bethesda, MD 20892 USA.
EM benjamin.basile@nih.gov
NR 29
TC 0
Z9 0
U1 2
U2 10
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015,
SWITZERLAND
SN 1664-1078
J9 FRONT PSYCHOL
JI Front. Psychol.
PD FEB 4
PY 2015
VL 6
AR 75
DI 10.3389/fpsyg.2015.00075
PG 2
WC Psychology, Multidisciplinary
SC Psychology
GA CA4BL
UT WOS:000348849100001
PM 25699000
ER
PT J
AU Hunsberger, JG
Chibane, FL
Elkahloun, AG
Henderson, R
Singh, R
Lawson, J
Cruceanu, C
Nagarajan, V
Turecki, G
Squassina, A
Medeiros, CD
Del Zompo, M
Rouleau, GA
Alda, M
Chuang, DM
AF Hunsberger, J. G.
Chibane, F. L.
Elkahloun, A. G.
Henderson, R.
Singh, R.
Lawson, J.
Cruceanu, C.
Nagarajan, V.
Turecki, G.
Squassina, A.
Medeiros, C. D.
Del Zompo, M.
Rouleau, G. A.
Alda, M.
Chuang, D-M
TI Novel integrative genomic tool for interrogating lithium response in
bipolar disorder
SO TRANSLATIONAL PSYCHIATRY
LA English
DT Article
ID MAPPING SUSCEPTIBILITY GENES; SPECTRUM DISORDER; MOOD STABILIZERS;
EXPRESSION; IDENTIFICATION; LYMPHOBLASTS; PREVALENCE; BIOMARKERS; CELLS
AB We developed a novel integrative genomic tool called GRANITE (Genetic Regulatory Analysis of Networks Investigational Tool Environment) that can effectively analyze large complex data sets to generate interactive networks. GRANITE is an open-source tool and invaluable resource for a variety of genomic fields. Although our analysis is confined to static expression data, GRANITE has the capability of evaluating time-course data and generating interactive networks that may shed light on acute versus chronic treatment, as well as evaluating dose response and providing insight into mechanisms that underlie therapeutic versus sub-therapeutic doses or toxic doses. As a proof-of-concept study, we investigated lithium (Li) response in bipolar disorder (BD). BD is a severe mood disorder marked by cycles of mania and depression. Li is one of the most commonly prescribed and decidedly effective treatments for many patients (responders), although its mode of action is not yet fully understood, nor is it effective in every patient (non-responders). In an in vitro study, we compared vehicle versus chronic Li treatment in patient-derived lymphoblastoid cells (LCLs) (derived from either responders or non-responders) using both microRNA (miRNA) and messenger RNA gene expression profiling. We present both Li responder and non-responder network visualizations created by our GRANITE analysis in BD. We identified by network visualization that the Let-7 family is consistently downregulated by Li in both groups where this miRNA family has been implicated in neurodegeneration, cell survival and synaptic development. We discuss the potential of this analysis for investigating treatment response and even providing clinicians with a tool for predicting treatment response in their patients, as well as for providing the industry with a tool for identifying network nodes as targets for novel drug discovery.
C1 [Hunsberger, J. G.; Chibane, F. L.; Chuang, D-M] NIMH, Mol Neurobiol Sect, NIH, Bethesda, MD 20892 USA.
[Elkahloun, A. G.] NHGRI, NIH, Bethesda, MD 20892 USA.
[Henderson, R.; Nagarajan, V.] NIAID, BCBB, OCICB, NIH, Bethesda, MD 20892 USA.
[Singh, R.] Lockheed Martin Corp, IS&GS, Bethesda, MD USA.
[Lawson, J.] KG Sci Associates LLC, San Diego, CA USA.
[Cruceanu, C.; Turecki, G.; Medeiros, C. D.] McGill Univ, Douglas Mental Hlth Inst, McGill Grp Suicide Studies, Montreal, PQ, Canada.
[Cruceanu, C.; Rouleau, G. A.] McGill Univ, Montreal Neurol Inst, Montreal, PQ, Canada.
[Squassina, A.; Del Zompo, M.] Univ Cagliari, Dept Biomed Sci, Sect Neurosci & Clin Pharmacol, Cagliari, Italy.
[Alda, M.] Dalhousie Univ, Dept Psychiat, Halifax, NS, Canada.
RP Hunsberger, JG (reprint author), NIMH, Mol Neurobiol Sect, NIH, 10 Ctr Dr MSC 1363, Bethesda, MD 20892 USA.
EM hunsbergerjg@gmail.com; chuang@mail.nih.gov
OI Squassina, Alessio/0000-0001-7415-7607
FU NIMH; Office of Cyber Infrastructure and Computational Biology of NIAID,
NIH
FX We would like to acknowledge the support of the Intramural Research
Program of the NIMH, and the Office of Cyber Infrastructure and
Computational Biology of NIAID, NIH. We would also like to acknowledge
the technical support kindly provided by Weiwei Wu for array processing,
and Peter Leeds for editorial suggestions.
NR 34
TC 4
Z9 4
U1 2
U2 2
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 2158-3188
J9 TRANSL PSYCHIAT
JI Transl. Psychiatr.
PD FEB 3
PY 2015
VL 5
AR e504
DI 10.1038/tp.2014.139
PG 8
WC Psychiatry
SC Psychiatry
GA DA2UF
UT WOS:000367651400004
PM 25646593
ER
PT J
AU Chen, X
Zhu, YQ
Li, FH
Zheng, ZY
Chang, EC
Ma, JW
Wong, STC
AF Chen, Xu
Zhu, Yanqiao
Li, Fuhai
Zheng, Ze-Yi
Chang, Eric C.
Ma, Jinwen
Wong, Stephen T. C.
TI Accurate segmentation of touching cells in multi-channel microscopy
images with geodesic distance based clustering
SO NEUROCOMPUTING
LA English
DT Article
DE Cell segmentation; Color information; Riemannian metric; Clustering
analysis; Quantitative evaluation
ID AUTOMATED MODEL SELECTION; PHASE IDENTIFICATION; GAUSSIAN MIXTURE;
CLASSIFICATION; TRACKING; CYCLE
AB Multi-channel microscopy images have been widely used for drug and target discovery in biomedical studies by investigating morphological changes of individual cells. However, it is still challenging to segment densely touching individual cells in such images accurately and automatically. Herein, we propose a geodesic distance based clustering approach to efficiently segmenting densely touching cells in multi-channel microscopy images. Specifically, an adaptive learning scheme is introduced to iteratively adjust the clustering centers which can significantly improve the segmentation accuracy of cell boundaries. Moreover, a novel seed selection procedure based on nuclei segmentation is suggested to determine the true number of cells in an image. To validate this proposed method, we applied it to segment the touching Madin-Darby Canine Kidney (MDCK) epithelial cells in multi-channel images for measuring the distinct N-Ras protein expression patterns inside individual cells. The experimental results demonstrated its advantages on accurately segmenting massive touching cells, as well as the robustness to the low signal-to-noise ratio and varying intensity contrasts in multi-channel microscopy images. Moreover, the quantitative comparison showed its superiority over the typical existing cell segmentation methods. (C) 2014 Elsevier B.V. All rights reserved.
C1 [Chen, Xu; Zhu, Yanqiao; Ma, Jinwen] Peking Univ, Dept Informat Sci, Sch Math Sci, Beijing 100871, Peoples R China.
[Chen, Xu; Zhu, Yanqiao; Ma, Jinwen] Peking Univ, LMAM, Beijing 100871, Peoples R China.
[Chen, Xu] PLA, Unit 91635, Beijing, Peoples R China.
[Li, Fuhai; Wong, Stephen T. C.] Cornell Univ, NCI Ctr Modeling Canc Dev, Dept Syst Med & Bioengn, Methodist Hosp Res Inst,Weill Cornell Med Coll, Houston, TX 77030 USA.
[Zheng, Ze-Yi; Chang, Eric C.] Baylor Coll Med, Dept Mol & Cellular Biol, Breast Ctr, Houston, TX 77030 USA.
RP Ma, JW (reprint author), Peking Univ, Dept Informat Sci, Sch Math Sci, Beijing 100871, Peoples R China.
EM jwma@math.pku.edu.cn
FU Natural Science Foundation of China [61171138]; NIH [U54 CA149196-01,
R01LM009161]; John S Dunn Research Foundation
FX This work was supported by the Natural Science Foundation of China for
Grants 61171138, NIH U54 CA149196-01, R01LM009161 and John S Dunn
Research Foundation.
NR 30
TC 2
Z9 2
U1 3
U2 5
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0925-2312
EI 1872-8286
J9 NEUROCOMPUTING
JI Neurocomputing
PD FEB 3
PY 2015
VL 149
BP 39
EP 47
DI 10.1016/j.neucom.2014.01.061
PN A
PG 9
WC Computer Science, Artificial Intelligence
SC Computer Science
GA CP6WL
UT WOS:000360028800006
ER
PT J
AU Qian, X
Brinton, LA
Schairer, C
Matthews, CE
AF Qian, X.
Brinton, L. A.
Schairer, C.
Matthews, C. E.
TI Sleep duration and breast cancer risk in the Breast Cancer Detection
Demonstration Project follow-up cohort
SO BRITISH JOURNAL OF CANCER
LA English
DT Article
DE sleep; breast cancer; hormone receptor-positive breast cancer; hormone
receptor-negative breast cancer
ID MELATONIN; WOMEN
AB Background: Short sleep has been hypothesised to increase the risk of breast cancer. However, little is known about the association between sleep and different subtypes of breast cancer defined by hormone receptor status.
Methods: Among 40013 women in the Breast Cancer Detection Demonstration Project, including 1846 incident breast cancer cases, we prospectively examined self-reported weekday and weekend sleep duration in relation to breast cancer risk. We used multivariate Cox proportional hazards regression models to estimate relative risks (RRs) and 95% confidence intervals (CIs).
Results: We found no association between sleep and overall breast cancer. However, we observed a decreased risk of ER+PR+ breast cancer (RR (<6) (vs) (8-9h) (95% CI): 0.54 (0.31, 0.93), P for trend, 0.003) with shorter sleep duration.
Conclusions: Our finding does not support an association between sleep duration and overall breast cancer risk. However, the effect of sleep on different subtypes of breast cancer deserves further investigation.
C1 [Qian, X.; Matthews, C. E.] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20892 USA.
[Brinton, L. A.] NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA.
[Schairer, C.] NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA.
RP Qian, X (reprint author), NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20892 USA.
EM qian.xiao@nih.gov
RI Brinton, Louise/G-7486-2015
OI Brinton, Louise/0000-0003-3853-8562
NR 18
TC 1
Z9 1
U1 0
U2 3
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 FEB 3
PY 2015
VL 112
IS 3
BP 567
EP 571
DI 10.1038/bjc.2014.600
PG 5
WC Oncology
SC Oncology
GA CB1QP
UT WOS:000349403200022
PM 25474248
ER
PT J
AU Cook, MB
Freedman, ND
Gamborg, M
Sorensen, TIA
Baker, JL
AF Cook, M. B.
Freedman, N. D.
Gamborg, M.
Sorensen, T. I. A.
Baker, J. L.
TI Childhood body mass index in relation to future risk of oesophageal
adenocarcinoma
SO BRITISH JOURNAL OF CANCER
LA English
DT Article
DE (MeSH): body height; body mass index; body weight; cohort studies;
oesophageal neoplasms
ID GASTROESOPHAGEAL-REFLUX DISEASE; INTERNATIONAL BEACON CONSORTIUM;
GASTRIC CARDIA; UNITED-STATES; FOLLOW-UP; BARRETTS-ESOPHAGUS; METABOLIC
SYNDROME; POOLED ANALYSIS; BIRTH COHORT; OBESITY
AB Background: Middle-aged obese adults are at substantially elevated risk of oesophageal adenocarcinoma. It is unclear whether this risk originates earlier in life.
Methods: We assessed associations between childhood body mass index (BMI) and height-measured annually between ages 7 and 13-with adult oesophageal adenocarcinoma in a cohort from the Copenhagen School Health Records Register. Analyses included 255053 children born during 1930-1971. Danish Cancer Registry linkage provided outcomes. We calculated hazard ratios (HRs) and 95% confidence intervals (CIs) using Cox proportional hazards regression.
Results: During 5.4 million person-years of follow-up, 254 (216 males) incident oesophageal adenocarcinomas occurred. At each examined age, cancer risk increased linearly per unit BMI z-score, although associations were only statistically significant for ages 9-13. The HR for the age of 13 years was 1.31 (95% CI: 1.13, 1.51) per unit BMI z-score. Associations were similar in men and women and across birth cohorts. Childhood height was not related to cancer risk in men but was in women, although these analyses included just 38 female cases. HRs per unit height z-score at the age of 13 years were 1.04 (0.90, 1.19) in males and 1.77 (1.27, 2.47) in females, with similar results observed at the other examined ages.
Conclusion: Individuals with higher childhood BMI were at elevated risk of oesophageal adenocarcinoma, even though these cancers occurred many decades later in life. Although the mechanisms require further investigation, our findings provide additional evidence for the long-term health risks of childhood obesity.
C1 [Cook, M. B.; Freedman, N. D.] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA.
[Gamborg, M.; Sorensen, T. I. A.; Baker, J. L.] Bispebjerg & Frederiksberg Hosp, Inst Prevent Med, Copenhagen, Denmark.
[Sorensen, T. I. A.; Baker, J. L.] Univ Copenhagen, Fac Hlth & Med Sci, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark.
RP Baker, JL (reprint author), Bispebjerg & Frederiksberg Hosp, Inst Prevent Med, Copenhagen, Denmark.
EM jennifer.lyn.baker@regionh.dk
RI Freedman, Neal/B-9741-2015; Cook, Michael/A-5641-2009; Baker,
Jennifer/F-1917-2010
OI Freedman, Neal/0000-0003-0074-1098; Cook, Michael/0000-0002-0533-7302;
Baker, Jennifer/0000-0002-9649-6615
FU Intramural Program of the National Cancer Institute, National Institutes
of Health, Department of Health and Human Services; European Research
Council-European Union's Seventh Framework Programme (FP)/ERC [281418]
FX This study was funded by the Intramural Program of the National Cancer
Institute, National Institutes of Health, Department of Health and Human
Services and by the European Research Council-European Union's Seventh
Framework Programme (FP/2007-2013)/ERC Grant Agreement no. 281418,
childgrowth2cancer to JLB.
NR 47
TC 8
Z9 8
U1 0
U2 2
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 FEB 3
PY 2015
VL 112
IS 3
BP 601
EP 607
DI 10.1038/bjc.2014.646
PG 7
WC Oncology
SC Oncology
GA CB1QP
UT WOS:000349403200026
PM 25562436
ER
PT J
AU Eddy, MT
Andreas, L
Teijido, O
Su, YC
Clark, L
Noskov, SY
Wagner, G
Rostovtseva, TK
Griffin, RG
AF Eddy, Matthew T.
Andreas, Loren
Teijido, Oscar
Su, Yongchao
Clark, Lindsay
Noskov, Sergei Y.
Wagner, Gerhard
Rostovtseva, Tatiana K.
Griffin, Robert G.
TI Magic Angle Spinning Nuclear Magnetic Resonance Characterization of
Voltage-Dependent Anion Channel Gating in Two-Dimensional Lipid
Crystalline Bilayers
SO BIOCHEMISTRY
LA English
DT Article
ID MITOCHONDRIAL OUTER-MEMBRANE; VDAC1 N-TERMINUS; SELECTIVE CHANNEL;
CROSS-POLARIZATION; ION SELECTIVITY; ALPHA-HEMOLYSIN; CELL-DEATH;
DYNAMICS; PROTEIN; NMR
AB The N-terminus of the voltage-dependent anion channel (VDAC) has been proposed to contain the mechanistically important gating helices that modulate channel opening and closing. In this study, we utilize magic angle spinning nuclear magnetic resonance (MAS NMR) to determine the location and structure of the N-terminus for functional channels in lipid bilayers by measuring long-range C-13-C-13 distances between residues in the N-terminus and other domains of VDAC reconstituted into DMPC lipid bilayers. Our structural studies show that the distance between A14 C-beta in the N-terminal helix and S193 C beta is similar to 4-6 angstrom. Furthermore, VDAC phosphorylation by a mitochondrial kinase at residue S193 has been claimed to delay mitochondrial cell death by causing a conformational change that closes the channel, and a VDAC-Ser193Glu mutant has been reported to show properties very similar to those of phosphorylated VDAC in a cellular context. We expressed VDAC-S193E and reconstituted it into DMPC lipid bilayers. Two-dimensional C-13-C-13 correlation experiments showed chemical shift perturbations for residues located in the N-terminus, indicating possible structural perturbations to that region. However, electrophysiological data recorded on VDAC-S193E showed that channel characteristics were identical to those of wild type samples, indicating that phosphorylation of S193 does not directly affect channel gating. The combination of NMR and electrophysiological results allows us to discuss the validity of proposed gating models.
C1 [Eddy, Matthew T.; Andreas, Loren; Su, Yongchao; Clark, Lindsay; Griffin, Robert G.] MIT, Dept Chem, Cambridge, MA 02139 USA.
[Eddy, Matthew T.; Andreas, Loren; Su, Yongchao; Clark, Lindsay; Griffin, Robert G.] MIT, Francis Bitter Magnet Lab, Cambridge, MA 02139 USA.
[Teijido, Oscar; Noskov, Sergei Y.; Rostovtseva, Tatiana K.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Phys Biol, NIH, Bethesda, MD 20892 USA.
[Noskov, Sergei Y.] Univ Calgary, Dept Biol Sci, Ctr Mol Simulat, Calgary, AB T2N 1N4, Canada.
[Wagner, Gerhard] Harvard Univ, Sch Med, Dept Mol Pharmacol & Biochem, Boston, MA 02115 USA.
RP Griffin, RG (reprint author), MIT, Dept Chem, Cambridge, MA 02139 USA.
EM rgg@mit.edu
RI Su, Yongchao/B-6749-2009
OI Su, Yongchao/0000-0001-5063-3218
FU National Institutes of Health (NIH) [EB001960, EB002026, GM075879];
National Sciences and Engineering Research Council of Canada (NSERC)
[RGPIN-315019]; Alberta Innovates Technology Futures (AITF) Strategic
Chair in BioMolecular Simulations (Centre for Molecular Simulation);
Eunice Kennedy Shriver National Institute of Child Health and Human
Development (NIH)
FX This research was supported by National Institutes of Health (NIH)
Grants EB001960, EB002026 (R.G.G.), and GM075879 (G.W.). S.Y.N. was
supported by the National Sciences and Engineering Research Council of
Canada (NSERC) (Discovery Grant RGPIN-315019) and the Alberta Innovates
Technology Futures (AITF) Strategic Chair in BioMolecular Simulations
(Centre for Molecular Simulation). The Intramural Research Program of
the Eunice Kennedy Shriver National Institute of Child Health and Human
Development (NIH) supported O.T. and T.K.R.
NR 56
TC 11
Z9 11
U1 1
U2 9
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0006-2960
J9 BIOCHEMISTRY-US
JI Biochemistry
PD FEB 3
PY 2015
VL 54
IS 4
BP 994
EP 1005
DI 10.1021/bi501260r
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA CA6WZ
UT WOS:000349059400005
PM 25545271
ER
PT J
AU Bergeron, JRC
Sgourakis, NG
AF Bergeron, Julien R. C.
Sgourakis, Nikolaos G.
TI Type IV Pilus: One Architectural Problem, Many Structural Solutions
SO STRUCTURE
LA English
DT Editorial Material
AB Type IV pili are long appendages found at the surface of many bacteria, composed of an oligomerized pilin protein and involved in processes such as adherence, motility and DNA transfer. In this issue of Structure, Piepenbrink and colleagues report the first structure a major pilin from a Gram-positive bacterium, revealing an unprecedented stabilization mechanism that may have implications for pilus evolution.
C1 [Bergeron, Julien R. C.] Univ British Columbia, Dept Biochem & Mol Biol, Vancouver, BC V6T 1Z3, Canada.
[Bergeron, Julien R. C.] Univ British Columbia, Ctr Blood Res, Vancouver, BC V6T 1Z3, Canada.
[Sgourakis, Nikolaos G.] NIDDK, NIH, Bethesda, MD 20892 USA.
RP Sgourakis, NG (reprint author), NIDDK, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM nikolaos.sgourakis@nih.gov
NR 9
TC 0
Z9 0
U1 1
U2 6
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0969-2126
EI 1878-4186
J9 STRUCTURE
JI Structure
PD FEB 3
PY 2015
VL 23
IS 2
BP 253
EP 255
DI 10.1016/j.str.2015.01.004
PG 3
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA CB1QJ
UT WOS:000349402500003
PM 25651057
ER
PT J
AU Tong, Q
Cui, GF
Botuyan, MV
Rothbart, SB
Hayashi, R
Musselman, CA
Singh, N
Appella, E
Strahl, BD
Mer, G
Kutateladze, TG
AF Tong, Qiong
Cui, Gaofeng
Botuyan, Maria Victoria
Rothbart, Scott B.
Hayashi, Ryo
Musselman, Catherine A.
Singh, Namit
Appella, Ettore
Strahl, Brian D.
Mer, Georges
Kutateladze, Tatiana G.
TI Structural Plasticity of Methyllysine Recognition by the Tandem Tudor
Domain of 53BP1
SO STRUCTURE
LA English
DT Article
ID LYSINE METHYLATION; DNA-REPAIR; TUMOR-SUPPRESSOR; CHEMICAL-SHIFT; P53
ACTIVITY; BINDING; PROTEIN; ACTIVATION; REPRESSION; CHROMATIN
AB p53 is dynamically regulated through various post-translational modifications (PTMs), which differentially modulate its function and stability. The dimethylated marks p53K370me2 and p53K382me2 are associated with p53 activation or stabilization and both are recognized by the tandem Tudor domain (TTD) of 53BP1, a p53 cofactor. Here we detail the molecular mechanisms for the recognition of p53K370me2 and p53K382me2 by 53BP1. The solution structures of TTD in complex with the p53K370me2 and p53K382me2 peptides show a remarkable plasticity of 53BP1 in accommodating these diverse dimethyllysine-containing sequences. We demonstrate that dimeric TTDs are capable of interacting with the two PTMs on a single p53K370me2K382me2 peptide, greatly strengthening the 53BP1-p53 interaction. Analysis of binding affinities of TTD toward methylated p53 and histones reveals strong preference of 53BP1 for p53K382me2, H4K20me2, and H3K36me2 and suggests a possible role of multivalent contacts of 53BP1 in p53 targeting to and accumulation at the sites of DNA damage.
C1 [Tong, Qiong; Musselman, Catherine A.; Kutateladze, Tatiana G.] Univ Colorado, Sch Med, Dept Pharmacol, Aurora, CO 80045 USA.
[Cui, Gaofeng; Botuyan, Maria Victoria; Singh, Namit; Mer, Georges] Mayo Clin, Dept Biochem & Mol Biol, Rochester, MN 55905 USA.
[Rothbart, Scott B.; Strahl, Brian D.] Univ N Carolina, Sch Med, Dept Biochem & Biophys, Chapel Hill, NC 27599 USA.
[Rothbart, Scott B.; Strahl, Brian D.] Univ N Carolina, Sch Med, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA.
[Hayashi, Ryo; Appella, Ettore] NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Mer, G (reprint author), Mayo Clin, Dept Biochem & Mol Biol, Rochester, MN 55905 USA.
EM mer.georges@mayo.edu; tatiana.kutateladze@ucdenver.edu
RI Strahl, Brian/C-7601-2012
OI Strahl, Brian/0000-0002-4947-6259
FU NIH [GM101664, CA132878, GM110058, CA181343]; Mayo Clinic SPORE NCI
grants [P50CA116201, P50CA108961]; Center for Cancer Research, National
Cancer Institute, NIH
FX This research is supported by grants from the NIH, GM101664 (T. G. K.),
CA132878 (G. M.), GM110058 (B. D. S.) and CA181343 (S. B. R.). G. M.
acknowledges partial support from the Mayo Clinic SPORE NCI grants
P50CA116201 and P50CA108961. This research is also supported in part by
the Intramural Research Program of the Center for Cancer Research,
National Cancer Institute, NIH (EA).
NR 50
TC 6
Z9 6
U1 1
U2 9
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0969-2126
EI 1878-4186
J9 STRUCTURE
JI Structure
PD FEB 3
PY 2015
VL 23
IS 2
BP 312
EP 321
DI 10.1016/j.str.2014.11.013
PG 10
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA CB1QJ
UT WOS:000349402500010
PM 25579814
ER
PT J
AU Tong, Q
Mazur, SJ
Rincon-Arano, H
Rothbart, SB
Kuznetsov, DM
Cui, GF
Liu, WH
Gete, Y
Klein, BJ
Jenkins, L
Mer, G
Kutateladze, AG
Strahl, BD
Groudine, M
Appella, E
Kutateladze, TG
AF Tong, Qiong
Mazur, Sharlyn J.
Rincon-Arano, Hector
Rothbart, Scott B.
Kuznetsov, Dmitry M.
Cui, Gaofeng
Liu, Wallace H.
Gete, Yantenew
Klein, Brianna J.
Jenkins, Lisa
Mer, Georges
Kutateladze, Andrei G.
Strahl, Brian D.
Groudine, Mark
Appella, Ettore
Kutateladze, Tatiana G.
TI An Acetyl-Methyl Switch Drives a Conformational Change in p53
SO STRUCTURE
LA English
DT Article
ID EMBRYONIC STEM-CELLS; DNA-DAMAGE; LYSINE METHYLATION; STRUCTURAL BASIS;
ACTIVATES P53; IN-VIVO; 53BP1; RECOGNITION; NEDDYLATION; MECHANISM
AB Individual posttranslational modifications (PTMs) of p53 mediate diverse p53-dependent responses; however, much less is known about the combinatorial action of adjacent modifications. Here, we describe crosstalk between the early DNA damage response mark p53K382me2 and the surrounding PTMs that modulate binding of p53 cofactors, including 53BP1 and p300. The 1.8 angstrom resolution crystal structure of the tandem Tudor domain (TTD) of 53BP1 in complex with p53 peptide acetylated at K381 and dimethylated at K382 (p53K381acK382me2) reveals that the dual PTM induces a conformational change in p53. The alpha-helical fold of p53K381acK382me2 positions the side chains of R379, K381ac, and K382me2 to interact with TTD concurrently, reinforcing a modular design of double PTM mimetics. Biochemical and nuclear magnetic resonance analyses show that other surrounding PTMs, including phosphorylation of serine/threonine residues of p53, affect association with TTD. Our findings suggest a novel PTM-driven conformation switch-like mechanism that may regulate p53 interactions with binding partners.
C1 [Tong, Qiong; Liu, Wallace H.; Klein, Brianna J.; Kutateladze, Tatiana G.] Univ Colorado, Sch Med, Dept Pharmacol, Aurora, CO 80045 USA.
[Mazur, Sharlyn J.; Gete, Yantenew; Jenkins, Lisa; Appella, Ettore] NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA.
[Rincon-Arano, Hector; Groudine, Mark] Fred Hutchinson Canc Res Ctr, Div Basic Sci, Seattle, WA 98109 USA.
[Rothbart, Scott B.; Strahl, Brian D.] Univ N Carolina, Dept Biochem & Biophys, Chapel Hill, NC 27599 USA.
[Rothbart, Scott B.; Strahl, Brian D.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA.
[Kuznetsov, Dmitry M.; Kutateladze, Andrei G.] Univ Denver, Dept Chem & Biochem, Denver, CO 80210 USA.
[Cui, Gaofeng; Mer, Georges] Mayo Clin, Coll Med, Dept Biochem & Mol Biol, Rochester, MN 55905 USA.
[Groudine, Mark] Univ Washington, Sch Med, Dept Radiat Oncol, Seattle, WA 98109 USA.
RP Kutateladze, TG (reprint author), Univ Colorado, Sch Med, Dept Pharmacol, Aurora, CO 80045 USA.
EM tatiana.kutateladze@ucdenver.edu
RI Strahl, Brian/C-7601-2012; Kuznetsov, Dmitry/K-7694-2013
OI Strahl, Brian/0000-0002-4947-6259; Kuznetsov, Dmitry/0000-0002-7956-1833
FU NIH [GM101664, HL65440, T32CA009657, GM110058, CA181343, CA132878,
GM093930]; Intramural Research Program of the National Cancer Institute,
NIH
FX We thank Siddhartha Roy and Catherine Musselman for help with
experiments and Jay Nix at beamline 4.2.2 of the ALS in Berkeley for
help with X-ray crystallographic data collection. We thank the ENCODE
Consortium and the ENCODE production laboratories (Ren Lab-LICR-SCSD)
that generated data sets used in this study. This research is supported
by grants from the NIH, GM101664 (T.G.K.), HL65440 (M.G.), T32CA009657
(H.R-A), GM110058 (B.D.S.), CA181343 (S.B.R.), CA132878 (G.M.), and
GM093930 (A.G.K.), and, in part, by the Intramural Research Program of
the National Cancer Institute, NIH (E.A.).
NR 36
TC 6
Z9 6
U1 1
U2 13
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0969-2126
EI 1878-4186
J9 STRUCTURE
JI Structure
PD FEB 3
PY 2015
VL 23
IS 2
BP 322
EP 331
DI 10.1016/j.str.2014.12.010
PG 10
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA CB1QJ
UT WOS:000349402500011
PM 25651062
ER
PT J
AU Lee, CT
Bendriem, RM
Kindberg, AA
Worden, LT
Williams, MP
Drgon, T
Mallon, BS
Harvey, BK
Richie, CT
Hamilton, RS
Chen, J
Errico, SL
Tsai, SYA
Uhl, GR
Freed, WJ
AF Lee, Chun-Ting
Bendriem, Raphael M.
Kindberg, Abigail A.
Worden, Lila T.
Williams, Melanie P.
Drgon, Tomas
Mallon, Barbara S.
Harvey, Brandon K.
Richie, Christopher T.
Hamilton, Rebecca S.
Chen, Jia
Errico, Stacie L.
Tsai, Shang-Yi A.
Uhl, George R.
Freed, William J.
TI Functional Consequences of 17q21.31/WNT3-WNT9B Amplification in hPSCs
with Respect to Neural Differentiation
SO CELL REPORTS
LA English
DT Article
ID PLURIPOTENT STEM-CELLS; COPY NUMBER VARIATION; DOPAMINERGIC-NEURONS;
PARKINSONS-DISEASE; IPS CELLS; HUMAN ES; PATHWAY; CULTURE; WNT-5A
AB Human pluripotent stem cell (hPSC) lines exhibit repeated patterns of genetic variation, which can alter in vitro properties as well as suitability for clinical use. We examined associations between copy-number variations (CNVs) on chromosome 17 and hPSC mesodiencephalic dopaminergic (mDA) differentiation. Among 24 hPSC lines, two karyotypically normal lines, BG03 and CT3, and BG01V2, with trisomy 17, exhibited amplification of the WNT3/WNT9B region and rapid mDA differentiation. In hPSC lines with amplified WNT3/WNT9B, basic fibroblast growth factor (bFGF) signaling through mitogen-activated protein kinase (MAPK)/ERK amplifies canonical WNT signaling by phosphorylating LRP6, resulting in enhanced undifferentiated proliferation. When bFGF is absent, noncanonical WNT signaling becomes dominant due to upregulation of SIAH2, enhancing JNK signaling and promoting loss of pluripotency. When bFGF is present during mDA differentiation, stabilization of canonical WNT signaling causes upregulation of LMX1A and mDA induction. Therefore, CNVs in 17q21.31, a "hot spot" for genetic variation, have multiple and complex effects on hPSC cellular phenotype.
C1 [Lee, Chun-Ting; Bendriem, Raphael M.; Kindberg, Abigail A.; Worden, Lila T.; Williams, Melanie P.; Drgon, Tomas; Harvey, Brandon K.; Richie, Christopher T.; Chen, Jia; Errico, Stacie L.; Tsai, Shang-Yi A.; Uhl, George R.; Freed, William J.] NIDA, Intramural Res Program, Dept Hlth & Human Serv, NIH, Baltimore, MD 21224 USA.
[Mallon, Barbara S.; Hamilton, Rebecca S.] NINDS, NIH Stem Cell Unit, Intramural Res Program, Dept Hlth & Human Serv,NIH, Bethesda, MD 20892 USA.
RP Lee, CT (reprint author), NIDA, Intramural Res Program, Dept Hlth & Human Serv, NIH, Baltimore, MD 21224 USA.
EM clee@mail.nih.gov
FU IRP of NIDA, NIH
FX This research was supported by the IRP of NIDA, NIH. We thank Teruo
Hayashi, Donna Walther, and Aaron Russell for assistance.
NR 27
TC 6
Z9 6
U1 0
U2 5
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 2211-1247
J9 CELL REP
JI Cell Reports
PD FEB 3
PY 2015
VL 10
IS 4
BP 616
EP 632
DI 10.1016/j.celrep.2014.12.050
PG 17
WC Cell Biology
SC Cell Biology
GA CB1QX
UT WOS:000349404100015
PM 25640183
ER
PT J
AU Millum, J
Sina, B
Glass, R
AF Millum, Joseph
Sina, Barbara
Glass, Roger
TI International Research Ethics Education
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Editorial Material
C1 [Millum, Joseph; Sina, Barbara; Glass, Roger] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Millum, Joseph] NIH, Dept Bioeth, Ctr Clin, Bethesda, MD 20892 USA.
RP Millum, J (reprint author), NIH, Clin Ctr Dept Bioeth, Fogarty Int Ctr, 10 Ctr Dr,10-1C118, Bethesda, MD 20892 USA.
EM millumj@cc.nih.gov
FU Intramural NIH HHS [Z99 CL999999]
NR 7
TC 2
Z9 2
U1 0
U2 2
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 FEB 3
PY 2015
VL 313
IS 5
BP 461
EP 462
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA CA7AV
UT WOS:000349070300006
PM 25647198
ER
PT J
AU Holcomb, JB
Tilley, BC
Baraniuk, S
Fox, EE
Wade, CE
Podbielski, JM
del Junco, DJ
Brasel, KJ
Bulger, EM
Callcut, RA
Cohen, MJ
Cotton, BA
Fabian, TC
Inaba, K
Kerby, JD
Muskat, P
O'Keeffe, T
Rizoli, S
Robinson, BRH
Scalea, TM
Schreiber, MA
Stein, DM
Weinberg, JA
Callum, JL
Hess, JR
Matijevic, N
Miller, CN
Pittet, JF
Hoyt, DB
Pearson, GD
Leroux, B
van Belle, G
AF Holcomb, John B.
Tilley, Barbara C.
Baraniuk, Sarah
Fox, Erin E.
Wade, Charles E.
Podbielski, Jeanette M.
del Junco, Deborah J.
Brasel, Karen J.
Bulger, Eileen M.
Callcut, Rachael A.
Cohen, Mitchell Jay
Cotton, Bryan A.
Fabian, Timothy C.
Inaba, Kenji
Kerby, Jeffrey D.
Muskat, Peter
O'Keeffe, Terence
Rizoli, Sandro
Robinson, Bryce R. H.
Scalea, Thomas M.
Schreiber, Martin A.
Stein, Deborah M.
Weinberg, Jordan A.
Callum, Jeannie L.
Hess, John R.
Matijevic, Nena
Miller, Christopher N.
Pittet, Jean-Francois
Hoyt, David B.
Pearson, Gail D.
Leroux, Brian
van Belle, Gerald
CA PROPPR Study Grp
TI Transfusion of Plasma, Platelets, and Red Blood Cells in a 1:1:1 vs a
1:1:2 Ratio and Mortality in Patients With Severe Trauma The PROPPR
Randomized Clinical Trial
SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
LA English
DT Article
ID DAMAGE CONTROL RESUSCITATION; MULTIPLE-ORGAN FAILURE;
RESPIRATORY-DISTRESS-SYNDROME; FRESH-FROZEN PLASMA; MASSIVE TRANSFUSION;
MAJOR TRAUMA; PRODUCTS; MULTICENTER; HEMORRHAGE; SURVIVAL
AB IMPORTANCE Severely injured patients experiencing hemorrhagic shock often require massive transfusion. Earlier transfusion with higher blood product ratios (plasma, platelets, and red blood cells), defined as damage control resuscitation, has been associated with improved outcomes; however, there have been no large multicenter clinical trials.
OBJECTIVE To determine the effectiveness and safety of transfusing patients with severe trauma and major bleeding using plasma, platelets, and red blood cells in a 1:1:1 ratio compared with a 1:1:2 ratio.
DESIGN, SETTING, AND PARTICIPANTS Pragmatic, phase 3, multisite, randomized clinical trial of 680 severely injured patients who arrived at 1 of 12 level I trauma centers in North America directly from the scene and were predicted to require massive transfusion between August 2012 and December 2013.
INTERVENTIONS Blood product ratios of 1:1:1 (338 patients) vs 1:1:2 (342 patients) during active resuscitation in addition to all local standard-of-care interventions (uncontrolled).
MAIN OUTCOMES AND MEASURES Primary outcomes were 24-hour and 30-day all-cause mortality. Prespecified ancillary outcomes included time to hemostasis, blood product volumes transfused, complications, incidence of surgical procedures, and functional status.
RESULTS No significant differences were detected in mortality at 24 hours (12.7% in 1:1:1 group vs 17.0% in 1:1:2 group; difference, -4.2%[95% CI, -9.6% to 1.1%]; P=.12) or at 30 days (22.4% vs 26.1%, respectively; difference, -3.7%[95% CI, -10.2% to 2.7%]; P=.26). Exsanguination, which was the predominant cause of death within the first 24 hours, was significantly decreased in the 1:1:1 group (9.2% vs 14.6% in 1:1:2 group; difference, -5.4%[95% CI, -10.4% to -0.5%]; P=.03). More patients in the 1:1:1 group achieved hemostasis than in the 1:1:2 group (86% vs 78%, respectively; P=.006). Despite the 1:1:1 group receiving more plasma (median of 7Uvs5U, P<.001) and platelets (12 U vs 6 U, P<.001) and similar amounts of red blood cells (9 U) over the first 24 hours, no differences between the 2 groups were found for the 23 prespecified complications, including acute respiratory distress syndrome, multiple organ failure, venous thromboembolism, sepsis, and transfusion-related complications.
CONCLUSIONS AND RELEVANCE Among patients with severe trauma and major bleeding, early administration of plasma, platelets, and red blood cells in a 1:1:1 ratio compared with a 1:1:2 ratio did not result in significant differences in mortality at 24 hours or at 30 days. However, more patients in the 1:1:1 group achieved hemostasis and fewer experienced death due to exsanguination by 24 hours. Even though there was an increased use of plasma and platelets transfused in the 1:1:1 group, no other safety differenceswere identified between the 2 groups.
C1 [Holcomb, John B.; Fox, Erin E.; Wade, Charles E.; Podbielski, Jeanette M.; del Junco, Deborah J.; Cotton, Bryan A.; Matijevic, Nena] Univ Texas Hlth Sci Ctr Houston, Ctr Translat Injury Res, Div Acute Care Surg, Sch Med,Dept Surg, Houston, TX 77030 USA.
[Tilley, Barbara C.; Baraniuk, Sarah] Univ Texas Hlth Sci Ctr Houston, Div Biostat, Sch Publ Hlth, Houston, TX 77030 USA.
[Brasel, Karen J.] Med Coll Wisconsin, Div Trauma & Crit Care, Dept Surg, Milwaukee, WI 53226 USA.
[Bulger, Eileen M.] Univ Washington, Sch Med, Dept Surg, Div Trauma & Crit Care, Seattle, WA 98195 USA.
[Callcut, Rachael A.; Cohen, Mitchell Jay] Univ Calif San Francisco, Sch Med, Dept Surg, Div Gen Surg, San Francisco, CA 94143 USA.
[Fabian, Timothy C.; Weinberg, Jordan A.] Univ Tennessee, Ctr Hlth Sci, Coll Med, Div Trauma & Surg Crit Care,Dept Surg, Memphis, TN 38163 USA.
[Inaba, Kenji] Univ So Calif, Div Trauma & Crit Care, Los Angeles, CA USA.
[Kerby, Jeffrey D.] Univ Alabama Birmingham, Sch Med, Dept Surg, Div Trauma Burns & Surg Crit Care, Birmingham, AL USA.
[Muskat, Peter; Robinson, Bryce R. H.] Univ Cincinnati, Coll Med, Dept Surg, Div Trauma Crit Care, Cincinnati, OH USA.
[O'Keeffe, Terence] Univ Arizona, Dept Surg, Div Trauma Crit Care & Emergency Surg, Tucson, AZ USA.
[Rizoli, Sandro] Univ Toronto, St Michaels Hosp, Toronto, ON, Canada.
[Scalea, Thomas M.; Stein, Deborah M.] Univ Maryland, Sch Med, Program Trauma, R Adams Cowley Shock Trauma Ctr, Baltimore, MD 21201 USA.
[Schreiber, Martin A.] Oregon Hlth & Sci Univ, Sch Med, Div Trauma Crit Care & Acute Care Surg, Portland, OR 97201 USA.
[Callum, Jeannie L.] Sunnybrook Hlth Sci Ctr, Sunnybrook Res Inst, Dept Clin Pathol, Toronto, ON M4N 3M5, Canada.
[Hess, John R.] Univ Washington, Sch Med, Dept Lab Med, Seattle, WA 98195 USA.
[Miller, Christopher N.] Univ Cincinnati, Coll Med, Dept Emergency Med, Cincinnati, OH USA.
[Pittet, Jean-Francois] Univ Alabama Birmingham, Sch Med, Dept Anesthesiol, Div Crit Care & Perioperat Med, Birmingham, AL USA.
[Hoyt, David B.] Amer Coll Surg, Chicago, IL USA.
[Pearson, Gail D.] NHLBI, Div Cardiovasc Sci, NIH, Bethesda, MD 20892 USA.
[Leroux, Brian; van Belle, Gerald] Univ Washington, Sch Publ Hlth, Dept Biostat, Seattle, WA 98195 USA.
[van Belle, Gerald] Univ Washington, Sch Publ Hlth, Dept Environm & Occupat Hlth Sci, Seattle, WA 98195 USA.
RP Holcomb, JB (reprint author), Univ Texas Hlth Sci Ctr Houston, Ctr Translat Injury Res, 6410 Fannin St, Houston, TX 77030 USA.
EM john.holcomb@uth.tmc.edu
RI Leroux, Brian/H-2254-2015
FU US National Heart, Lung, and Blood Institute [U01HL077863]; US
Department of Defense; Defence Research and Development Canada; Canadian
Institutes of Health Research-Institute of Circulatory and Respiratory
Health [CRR-120612]
FX This work was supported with grant U01HL077863 from the US National
Heart, Lung, and Blood Institute and funding from the US Department of
Defense, the Defence Research and Development Canada in partnership with
the Canadian Institutes of Health Research-Institute of Circulatory and
Respiratory Health (grant CRR-120612).
NR 60
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U1 3
U2 32
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 FEB 3
PY 2015
VL 313
IS 5
BP 471
EP 482
DI 10.1001/jama.2015.12
PG 12
WC Medicine, General & Internal
SC General & Internal Medicine
GA CA7AV
UT WOS:000349070300011
PM 25647203
ER
PT J
AU Tarasenko, TN
Rosas, OR
Singh, LN
Kristaponis, K
Vernon, H
McGuire, PJ
AF Tarasenko, Tatyana N.
Rosas, Odrick R.
Singh, Larry N.
Kristaponis, Kara
Vernon, Hilary
McGuire, Peter J.
TI A New Mouse Model of Mild Ornithine Transcarbamylase Deficiency (spf-j)
Displays Cerebral Amino Acid Perturbations at Baseline and upon Systemic
Immune Activation
SO PLOS ONE
LA English
DT Article
ID UREA CYCLE DISORDERS; AMMONIA METABOLISM; HYPERAMMONEMIA; MANAGEMENT;
MUTANT; EXPRESSION; ADULT
AB Ornithine transcarbamylase deficiency (OTCD, OMIM# 311250) is an inherited X-linked urea cycle disorder that is characterized by hyperammonemia and orotic aciduria. In this report, we describe a new animal model of OTCD caused by a spontaneous mutation in the mouse Otc gene (c.240T>A, p.K80N). This transversion in exon 3 of ornithine transcarbamylase leads to normal levels of mRNA with low levels of mature protein and is homologous to a mutation that has also been described in a single patient affected with late-onset OTCD. With higher residual enzyme activity, spf-J were found to have normal plasma ammonia and orotate. Baseline plasma amino acid profiles were consistent with mild OTCD: elevated glutamine, and lower citrulline and arginine. In contrast to WT, spf-J displayed baseline elevations in cerebral amino acids with depletion following immune challenge with polyinosinic: polycytidylic acid. Our results indicate that the mild spf-J mutation constitutes a new mouse model that is suitable for mechanistic studies of mild OTCD and the exploration of cerebral pathophysiology during acute decompensation that characterizes proximal urea cycle dysfunction in humans.
C1 [Tarasenko, Tatyana N.; Singh, Larry N.; McGuire, Peter J.] NHGRI, NIH, Bethesda, MD 20892 USA.
Univ Cent Caribe, Bayamon, PR USA.
[Kristaponis, Kara] Johns Hopkins Univ, Kennedy Krieger Inst, Dept Neurogenet, Baltimore, MD USA.
[Vernon, Hilary] Johns Hopkins Univ, Kennedy Krieger Inst, Baltimore, MD USA.
RP McGuire, PJ (reprint author), NHGRI, NIH, Bethesda, MD 20892 USA.
EM peter.mcguire@nih.gov
FU intramural research program of the National Institutes of Health;
Kennedy Kreiger Institute at Johns Hopkins University
FX Work performed by T.N.T., L.N.S., O.R.R., and P.J.M. was supported by
the intramural research program of the National Institutes of Health.
Work performed by H.V. and K.K. was supported by institutional funding
from the Kennedy Kreiger Institute at Johns Hopkins University. The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 31
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U1 0
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 FEB 3
PY 2015
VL 10
IS 2
AR e0116594
DI 10.1371/journal.pone.0116594
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CA3QZ
UT WOS:000348822600029
PM 25647322
ER
PT J
AU Remaley, AT
AF Remaley, Alan T.
TI HDL Cholesterol/HDL Particle Ratio A New Measure of HDL Function?
SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
LA English
DT Editorial Material
DE biomarkers; cardiovascular risk; cholesterol; HDL; NMR
ID DENSITY-LIPOPROTEIN CHOLESTEROL; MAGNETIC-RESONANCE-SPECTROSCOPY;
ATHEROSCLEROSIS; EVENTS; EFFLUX; TRANSPORT; NUMBER; RISK
C1 NIH, Bethesda, MD 20892 USA.
RP Remaley, AT (reprint author), NIH, Bldg 10,Room 2C-433,10 Ctr Dr, Bethesda, MD 20892 USA.
EM aremaley1@nhlbi.nih.gov
NR 19
TC 2
Z9 2
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 FEB 3
PY 2015
VL 65
IS 4
BP 364
EP 366
DI 10.1016/j.jacc.2014.11.018
PG 3
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA CA1IR
UT WOS:000348666800008
PM 25634835
ER
PT J
AU Ramphul, UN
Garver, LS
Molina-Cruz, A
Canepa, GE
Barillas-Mury, C
AF Ramphul, Urvashi N.
Garver, Lindsey S.
Molina-Cruz, Alvaro
Canepa, Gaspar E.
Barillas-Mury, Carolina
TI Plasmodium falciparum evades mosquito immunity by disrupting
JNK-mediated apoptosis of invaded midgut cells
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE malaria transmission; Plasmodium; JNK apoptosis; mosquito immunity;
immune evasion
ID NF-KAPPA-B; ANOPHELES-GAMBIAE; SIGNALING PATHWAYS; OOKINETE INVASION;
SCAFFOLD PROTEIN; FACTOR RELISH; DROSOPHILA; ACTIVATION; INHIBITOR;
NITRATION
AB The malaria parasite, Plasmodium, must survive and develop in the mosquito vector to be successfully transmitted to a new host. The Plasmodium falciparum Pfs47 gene is critical for malaria transmission. Parasites that express Pfs47 (NF54 WT) evade mosquito immunity and survive, whereas Pfs47 knockouts (KO) are efficiently eliminated by the complement-like system. Two alternative approaches were used to investigate the mechanism of action of Pfs47 on immune evasion. First, we examined whether Pfs47 affected signal transduction pathways mediating mosquito immune responses, and show that the Jun-N-terminal kinase (JNK) pathway is a key mediator of Anopheles gambiae antiplasmodial responses to P. falciparum infection and that Pfs47 disrupts JNK signaling. Second, we used microarrays to compare the global transcriptional responses of A. gambiae midguts to infection with WT and KO parasites. The presence of Pfs47 results in broad and profound changes in gene expression in response to infection that are already evident 12 h postfeeding, but become most prominent at 26 h postfeeding, the time when ookinetes invade the mosquito midgut. Silencing of 15 differentially expressed candidate genes identified caspase-S2 as a key effector of Plasmodium elimination in parasites lacking Pfs47. We provide experimental evidence that JNK pathway regulates activation of caspases in Plasmodium- invaded midgut cells, and that caspase activation is required to trigger midgut epithelial nitration. Pfs47 alters the cell death pathway of invaded midgut cells by disrupting JNK signaling and prevents the activation of several caspases, resulting in an ineffective nitration response that makes the parasite undetectable by the mosquito complement-like system.
C1 [Ramphul, Urvashi N.; Garver, Lindsey S.; Molina-Cruz, Alvaro; Canepa, Gaspar E.; Barillas-Mury, Carolina] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA.
RP Barillas-Mury, C (reprint author), NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA.
EM cbarillas@niaid.nih.gov
OI Garver, Lindsey/0000-0003-2893-0130
FU Intramural Research Program of the Division of Intramural Research;
National Institute of Allergy and Infectious Diseases; National
Institutes of Health
FX We thank Andre Laughinghouse and Kevin Lee for insectary support; Jose
Luis Ramirez, Nitin Kamath, Rebecca Greene, Alejandro Padron, Ashley
Haile, and Noelle Pavlovic for experimental assistance; and Timothy
Myers, Qin Su, and the National Institute of Allergy and Infectious
Diseases Genomic Technologies Section for microarray hybridization and
scanning. This work was supported by the Intramural Research Program of
the Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, National Institutes of Health.
NR 46
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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 FEB 3
PY 2015
VL 112
IS 5
BP 1273
EP 1280
DI 10.1073/pnas.1423586112
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CA7HF
UT WOS:000349087700029
PM 25552553
ER
PT J
AU Battle, C
Ott, CM
Burnette, DT
Lippincott-Schwartz, J
Schmidt, CF
AF Battle, Christopher
Ott, Carolyn M.
Burnette, Dylan T.
Lippincott-Schwartz, Jennifer
Schmidt, Christoph F.
TI Intracellular and extracellular forces drive primary cilia movement
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE primary cilium; mechanosensing; ciliary motility; flexural rigidity;
active fluctuations
ID POLYCYSTIC KIDNEY-DISEASE; FLEXURAL RIGIDITY; EPITHELIAL-CELLS; BASAL
BODIES; GROWING MICROTUBULES; THERMAL FLUCTUATIONS; SENSORY ORGANELLE;
SPERM FLAGELLA; MYOSIN-II; CALCIUM
AB Primary cilia are ubiquitous, microtubule-based organelles that play diverse roles in sensory transduction in many eukaryotic cells. They interrogate the cellular environment through chemosensing, osmosensing, and mechanosensing using receptors and ion channels in the ciliary membrane. Little is known about the mechanical and structural properties of the cilium and how these properties contribute to ciliary perception. We probed the mechanical responses of primary cilia from kidney epithelial cells [Madin-Darby canine kidney-II (MDCK-II)], which sense fluid flow in renal ducts. We found that, on manipulation with an optical trap, cilia deflect by bending along their length and pivoting around an effective hinge located below the basal body. The calculated bending rigidity indicates weak microtubule doublet coupling. Primary cilia of MDCK cells lack interdoublet dynein motors. Nevertheless, we found that the organelles display active motility. 3D tracking showed correlated fluctuations of the cilium and basal body. These angular movements seemed random but were dependent on ATP and cytoplasmic myosin-II in the cell cortex. We conclude that force generation by the actin cytoskeleton surrounding the basal body results in active ciliary movement. We speculate that actin-driven ciliary movement might tune and calibrate ciliary sensory functions.
C1 [Battle, Christopher; Schmidt, Christoph F.] Univ Gottingen, Drittes Phys Inst, D-37077 Gottingen, Germany.
[Ott, Carolyn M.; Lippincott-Schwartz, Jennifer] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA.
[Burnette, Dylan T.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hu, NIH, Bethesda, MD 20892 USA.
[Burnette, Dylan T.] Vanderbilt Univ Sch Med, Dept Cell & Dev Biol, Nashville, TN 37232 USA.
RP Lippincott-Schwartz, J (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA.
EM lippincj@mail.nih.gov; cfs@physik3.gwdg.de
RI Schmidt, Christoph/G-3787-2011
OI Schmidt, Christoph/0000-0003-2864-6973
FU Intramural Program of the National Institutes of Health, National
Institute of Child Health and Human Development; Deutsche
Forschungsgemeinschaft [Sonderforschungsbereich 803,
Sonderforschungsbereich 937]; Center for Nanoscale Microscopy and
Molecular Physiology of the Brain; European Research Council [PF7
ERC-2013-AdG, 340528]; Gottingen Graduate School for Neurosciences,
Biophysics, and Molecular Biosciences
FX We thank Hiroaki Ishikawa, Claus Heussinger, Giovanni Marelli, and
Andrej Vilfan for helpful discussion and Andreas Janshoff for providing
us with the Madin-Darby canine kidney-II cell line. We acknowledge
discussions at the Woods Hole Marine Biology Laboratory. We also thank
Monica Bettencourt-Dias, Tristan Ursell, and Kimberly Yasutis for help
with early experiments monitoring cilia movement. Rafael Vilasmil from
the National Eye Institute Flow Cytometry Core sorted cells for this
study. This research was supported by the Intramural Program of the
National Institutes of Health, National Institute of Child Health and
Human Development; the Deutsche Forschungsgemeinschaft through
Sonderforschungsbereich 803 Project A7 and 937 Project A2; the Center
for Nanoscale Microscopy and Molecular Physiology of the Brain; and
European Research Council Grant PF7 ERC-2013-AdG, Project 340528 (to
C.F.S.). Fellowship funding was provided by the Gottingen Graduate
School for Neurosciences, Biophysics, and Molecular Biosciences.
NR 52
TC 3
Z9 3
U1 5
U2 26
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 FEB 3
PY 2015
VL 112
IS 5
BP 1410
EP 1415
DI 10.1073/pnas.1421845112
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CA7HF
UT WOS:000349087700052
PM 25605896
ER
PT J
AU Poruchynsky, MS
Komlodi-Pasztor, E
Trostel, S
Wilkerson, J
Regairaz, M
Pommier, Y
Zhang, X
Maity, TK
Robey, R
Burotto, M
Sackett, D
Guha, U
Fojo, AT
AF Poruchynsky, Marianne S.
Komlodi-Pasztor, Edina
Trostel, Shana
Wilkerson, Julia
Regairaz, Marie
Pommier, Yves
Zhang, Xu
Maity, Tapan Kumar
Robey, Robert
Burotto, Mauricio
Sackett, Dan
Guha, Udayan
Fojo, Antonio Tito
TI Microtubule-targeting agents augment the toxicity of DNA-damaging agents
by disrupting intracellular trafficking of DNA repair proteins
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE microtubule targeting agents; DNA-damaging agents; combination
chemotherapy; targeted therapies; DNA repair protein trafficking
ID METASTATIC PROSTATE-CANCER; ANDROGEN RECEPTOR; NUCLEAR ACCUMULATION;
MITOTIC ARREST; INCREASED SURVIVAL; CELLS; CHEMOTHERAPY; MITOSIS;
TUBULIN; INHIBITORS
AB The paradigm that microtubule-targeting agents (MTAs) cause cell death via mitotic arrest applies to rapidly dividing cells but cannot explain MTA activity in slowly growing human cancers. Many preferred cancer regimens combine a MTA with a DNA-damaging agent (DDA). We hypothesized that MTAs synergize with DDAs by interfering with trafficking of DNA repair proteins on interphase microtubules. We investigated nine proteins involved in DNA repair: ATM, ATR, DNA-PK, Rad50, Mre11, p95/NBS1, p53, 53BP1, and p63. The proteins were sequestered in the cytoplasm by vincristine and paclitaxel but not by an aurora kinase inhibitor, colocalized with tubulin by confocal microscopy and coimmunoprecipitated with the microtubule motor dynein. Furthermore, adding MTAs to radiation, doxorubicin, or etoposide led to more sustained gamma-H2AX levels. We conclude DNA damage-repair proteins traffic on microtubules and addition of MTAs sequesters them in the cytoplasm, explaining why MTA/DDA combinations are common anticancer regimens.
C1 [Poruchynsky, Marianne S.; Komlodi-Pasztor, Edina; Trostel, Shana; Wilkerson, Julia; Zhang, Xu; Maity, Tapan Kumar; Burotto, Mauricio; Guha, Udayan; Fojo, Antonio Tito] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Regairaz, Marie; Pommier, Yves; Robey, Robert] NCI, Dev Therapeut Branch, NIH, Bethesda, MD 20892 USA.
[Sackett, Dan] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Phys Biol, NIH, Bethesda, MD 20892 USA.
RP Fojo, AT (reprint author), NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM fojot@mail.nih.gov
OI Wilkerson, Julia/0000-0002-6965-0867
FU Intramural Research Program of the Eunice Kennedy Shriver National
Institute of Child Health and Human Development
FX We thank Yvona Ward, PhD, Head, Microscopy Core Facility, Center for
Cancer Research, National Cancer Institute, Cancer Cell Biology Program,
Bethesda, MD, for expert technical advice and assistance for the
immunofluorescence and confocal microscopy imaging experiments. This
work was supported in part by the Intramural Research Program of the
Eunice Kennedy Shriver National Institute of Child Health and Human
Development.
NR 39
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U1 4
U2 23
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 FEB 3
PY 2015
VL 112
IS 5
BP 1571
EP 1576
DI 10.1073/pnas.1416418112
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CA7HF
UT WOS:000349087700079
PM 25605897
ER
PT J
AU Riolo, MA
Rohani, P
AF Riolo, Maria A.
Rohani, Pejman
TI Combating pertussis resurgence: One booster vaccination schedule does
not fit all
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE pertussis; booster schedule; immunization; genetic algorithm
ID BORDETELLA-PERTUSSIS; DISEASE BURDEN; HERD-IMMUNITY; VACCINES;
EPIDEMIOLOGY; IMMUNIZATION; IMPACT; TRANSMISSION; EVOLUTION; EXEMPTIONS
AB Pertussis has reemerged as a major public health concern in many countries where it was once considered well controlled. Although the mechanisms responsible for continued pertussis circulation and resurgence remain elusive and contentious, many countries have nevertheless recommended booster vaccinations, the timing and number of which vary widely. Here, using a stochastic, age-stratified transmission model, we searched for cost-effective booster vaccination strategies using a genetic algorithm. We did so assuming four hypothesized mechanisms underpinning contemporary pertussis epidemiology: (I) insufficient coverage, (II) frequent primary vaccine failure, (III) waning of vaccine-derived protection, and (IV) vaccine "leakiness." For scenarios I-IV, successful booster strategies were identified and varied considerably by mechanism. Especially notable is the inability of booster schedules to alleviate resurgence when vaccines are leaky. Critically, our findings argue that the ultimate effectiveness of vaccine booster schedules will likely depend on correctly pinpointing the causes of resurgence, with misdiagnosis of the problem epidemiologically ineffective and economically costly.
C1 [Riolo, Maria A.] Univ Michigan, Dept Math, Ann Arbor, MI 48109 USA.
[Rohani, Pejman] Univ Michigan, Dept Ecol & Evolutionary Biol, Ann Arbor, MI 48109 USA.
[Riolo, Maria A.; Rohani, Pejman] Univ Michigan, Ctr Study Complex Syst, Ann Arbor, MI 48109 USA.
[Rohani, Pejman] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Riolo, MA (reprint author), Univ Michigan, Dept Math, Ann Arbor, MI 48109 USA.
EM mariolo@umich.edu
FU Research and Policy in Infectious Disease Dynamics Program of the
Science and Technology Directorate, Department of Homeland Security;
Fogarty International Center, NIH; NIH [R01AI101155]; Models of
Infectious Disease Agent Study, National Institute of General Medical
Sciences [U54-GM111274]
FX We thank Aaron King, Micaela Martinez-Bakker, Matthieu Domenech de
Celles, and Felicia Magpantay for stimulating discussion. We also thank
Alison Galvani, Meagan Fitzpatrick, and an anonymous reviewer for their
insightful comments on this manuscript. This work was supported by the
Research and Policy in Infectious Disease Dynamics Program of the
Science and Technology Directorate, Department of Homeland Security, the
Fogarty International Center, NIH; by a research grant from the NIH
(Grant R01AI101155); and by the Models of Infectious Disease Agent
Study, National Institute of General Medical Sciences (Grant
U54-GM111274).
NR 60
TC 9
Z9 9
U1 0
U2 13
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD FEB 3
PY 2015
VL 112
IS 5
BP E472
EP E477
DI 10.1073/pnas.1415573112
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CA7HF
UT WOS:000349087700014
PM 25605878
ER
PT J
AU Walmacq, C
Wang, LF
Chong, J
Scibelli, K
Lubkowska, L
Gnatt, A
Brooks, PJ
Wang, D
Kashlev, M
AF Walmacq, Celine
Wang, Lanfeng
Chong, Jenny
Scibelli, Kathleen
Lubkowska, Lucyna
Gnatt, Averell
Brooks, Philip J.
Wang, Dong
Kashlev, Mikhail
TI Mechanism of RNA polymerase II bypass of oxidative cyclopurine DNA
lesions
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE RNA polymerase II; translesion transcription; oxidative DNA damage;
transcriptional mutagenesis; transcription factor TFIIF
ID NUCLEOTIDE EXCISION-REPAIR; TRANSCRIPTIONAL MUTAGENESIS; TRANSLESION
SYNTHESIS; STRUCTURAL BASIS; HUMAN-CELLS; ELONGATION COMPLEX;
ATOMIC-RESOLUTION; DAMAGED DNA; A-RULE; FIDELITY
AB In human cells, the oxidative DNA lesion 8,5 '-cyclo-2 '-deoxyadenosine (CydA) induces prolonged stalling of RNA polymerase II (Pol II) followed by transcriptional bypass, generating both error-free and mutant transcripts with AMP misincorporated immediately downstream from the lesion. Here, we present biochemical and crystallographic evidence for the mechanism of CydA recognition. Pol II stalling results from impaired loading of the template base (5 ') next to CydA into the active site, leading to preferential AMP misincorporation. Such predominant AMP insertion, which also occurs at an abasic site, is unaffected by the identity of the 5 '-templating base, indicating that it derives from nontemplated synthesis according to an A rule known for DNA polymerases and recently identified for Pol II bypass of pyrimidine dimers. Subsequent to AMP misincorporation, Pol II encounters a major translocation block that is slowly overcome. Thus, the translocation block combined with the poor extension of the dA.rA mispair reduce transcriptional mutagenesis. Moreover, increasing the active-site flexibility by mutation in the trigger loop, which increases the ability of Pol II to accommodate the bulky lesion, and addition of transacting factor TFIIF facilitate CydA bypass. Thus, blocking lesion entry to the active site, translesion A rule synthesis, and translocation block are common features of transcription across different bulky DNA lesions.
C1 [Walmacq, Celine; Scibelli, Kathleen; Lubkowska, Lucyna; Kashlev, Mikhail] NCI, Ctr Canc Res, Frederick, MD 21702 USA.
[Wang, Lanfeng; Chong, Jenny; Wang, Dong] Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, La Jolla, CA 92093 USA.
[Gnatt, Averell] Biopolcore Inc, Baltimore, MD 21208 USA.
[Brooks, Philip J.] NIAAA, Neurogenet Lab, Bethesda, MD 20892 USA.
[Brooks, Philip J.] NIAAA, Div Metab & Hlth Effects, Bethesda, MD 20892 USA.
[Brooks, Philip J.] NIH, Off Rare Dis Res, Natl Ctr Adv Translat Sci, Bethesda, MD 20892 USA.
RP Wang, D (reprint author), Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, La Jolla, CA 92093 USA.
EM dongwang@ucsd.edu; kashlevm@mail.nih.gov
FU National Institutes of Health (NIH) Research Grant [GM102362]; Kimmel
Scholar Award from the Sidney Kimmel Foundation for Cancer Research;
Skaggs School of Pharmacy and Pharmaceutical Sciences, University of
California, San Diego; Intramural Research Program of the NIH, NCI
FX We thank Z. Burton and Y. Nedialkov for providing the recombinant human
TFIIF. P.J.B. thanks Tsu-Fan Cheng and Jinping Jia for generating
preliminary data. K.S. was a participant in the National Cancer
Institute (NCI) Summer Internship Program. D.W. acknowledges National
Institutes of Health (NIH) Research Grant GM102362, the Kimmel Scholar
Award from the Sidney Kimmel Foundation for Cancer Research, and
start-up funds from the Skaggs School of Pharmacy and Pharmaceutical
Sciences, University of California, San Diego, for support of this work.
M.K. acknowledges the Intramural Research Program of the NIH, NCI, for
support of this work.
NR 45
TC 8
Z9 8
U1 1
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 FEB 3
PY 2015
VL 112
IS 5
BP E410
EP E419
DI 10.1073/pnas.1415186112
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CA7HF
UT WOS:000349087700007
PM 25605892
ER
PT J
AU Hladik, F
Burgener, A
Ballweber, L
Gottardo, R
Vojtech, L
Fourati, S
Dai, JY
Cameron, MJ
Strobl, J
Hughes, SM
Hoesley, C
Andrew, P
Johnson, S
Piper, J
Friend, DR
Ball, TB
Cranston, RD
Mayer, KH
McElrath, MJ
McGowan, I
AF Hladik, Florian
Burgener, Adam
Ballweber, Lamar
Gottardo, Raphael
Vojtech, Lucia
Fourati, Slim
Dai, James Y.
Cameron, Mark J.
Strobl, Johanna
Hughes, Sean M.
Hoesley, Craig
Andrew, Philip
Johnson, Sherri
Piper, Jeanna
Friend, David R.
Ball, T. Blake
Cranston, Ross D.
Mayer, Kenneth H.
McElrath, M. Juliana
McGowan, Ian
TI Mucosal effects of tenofovir 1% gel
SO ELIFE
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; FEMALE GENITAL-TRACT; DNA COPY NUMBER;
MICROARRAY DATA; ILLUMINA MICROARRAY; TGF-BETA; EXPRESSION; CELLS; GENE;
BIOINFORMATICS
AB Tenofovir gel is being evaluated for vaginal and rectal pre-exposure prophylaxis against HIV transmission. Because this is a new prevention strategy, we broadly assessed its effects on the mucosa. In MTN-007, a phase-1, randomized, double-blinded rectal microbicide trial, we used systems genomics/proteomics to determine the effect of tenofovir 1% gel, nonoxynol-9 2% gel, placebo gel or no treatment on rectal biopsies (15 subjects/arm). We also treated primary vaginal epithelial cells from four healthy women with tenofovir in vitro. After seven days of administration, tenofovir 1% gel had broad-ranging effects on the rectal mucosa, which were more pronounced than, but different from, those of the detergent nonoxynol-9. Tenofovir suppressed anti-inflammatory mediators, increased T cell densities, caused mitochondrial dysfunction, altered regulatory pathways of cell differentiation and survival, and stimulated epithelial cell proliferation. The breadth of mucosal changes induced by tenofovir indicates that its safety over longer-term topical use should be carefully monitored.
C1 [Hladik, Florian; Vojtech, Lucia; Hughes, Sean M.] Univ Washington, Dept Obstet & Gynecol, Seattle, WA 98195 USA.
[Hladik, Florian; McElrath, M. Juliana] Univ Washington, Dept Med, Seattle, WA 98195 USA.
[McElrath, M. Juliana] Univ Washington, Dept Global Hlth, Seattle, WA 98195 USA.
[Gottardo, Raphael; Dai, James Y.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Hladik, Florian; Burgener, Adam; Ballweber, Lamar; Gottardo, Raphael; Dai, James Y.; Strobl, Johanna; McElrath, M. Juliana] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, Seattle, WA 98104 USA.
[Gottardo, Raphael] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA.
[Fourati, Slim; Cameron, Mark J.] Vaccine & Gene Therapy Inst Florida, Port St Lucie, FL 34987 USA.
[Ball, T. Blake] Univ Manitoba, Dept Med Microbiol, Winnipeg, MB, Canada.
[Burgener, Adam; Ball, T. Blake] Publ Hlth Agcy Canada, Natl HIV & Retrovirol Labs, Winnipeg, MB, Canada.
[Hoesley, Craig] Univ Alabama Birmingham, Birmingham, AL USA.
[Cranston, Ross D.; McGowan, Ian] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA.
[Andrew, Philip; Johnson, Sherri] FHI 360, Durham, NC USA.
[Piper, Jeanna] NIAID, Div Aids, NIH, Bethesda, MD 20892 USA.
[Friend, David R.] Eastern Virginia Med Sch, CONRAD, Arlington, VA 22209 USA.
[Mayer, Kenneth H.] Beth Israel Deaconess Med Ctr, Fenway Hlth, Boston, MA USA.
[Mayer, Kenneth H.] Harvard Univ, Sch Med, Boston, MA USA.
[Cranston, Ross D.; McGowan, Ian] Magee Womens Res Inst, Microbicide Trials Network, Pittsburgh, PA USA.
RP Hladik, F (reprint author), Univ Washington, Dept Obstet & Gynecol, Seattle, WA 98195 USA.
EM fhladik@fhcrc.org; imcgowan@pitt.edu
OI Fourati, Slim/0000-0001-6609-7587; Hughes, Sean/0000-0002-9409-9405;
Hladik, Florian/0000-0002-0375-2764; Vojtech, Lucia/0000-0003-2343-0719;
Cranston, Ross/0000-0002-2687-6217
FU National Institute of Allergy and Infectious Diseases of the National
Institutes of Health [U01AI068633, U19AI082637, R01HD51455]
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 U01AI068633 ( to Sharon Hillier),
U19AI082637 (to I. M.) and R01HD51455 (to F.H.). The content is solely
the responsibility of the authors and does not necessarily represent the
official views of the National Institutes of Health or CONRAD. The
funders had no role in data collection and analysis, and decision to
publish. Jeanna Piper, employee of the National Institute of Allergy and
Infectious Diseases, participated in design of the clinical study and
preparation of the manuscript.
NR 54
TC 7
Z9 7
U1 0
U2 0
PU ELIFE SCIENCES PUBLICATIONS LTD
PI CAMBRIDGE
PA SHERATON HOUSE, CASTLE PARK, CAMBRIDGE, CB3 0AX, ENGLAND
SN 2050-084X
J9 ELIFE
JI eLife
PD FEB 3
PY 2015
VL 4
AR e04525
DI 10.7554/eLife.04525
PG 48
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA CA3CN
UT WOS:000348783800001
ER
PT J
AU VieBrock, L
Evans, SM
Beyer, AR
Larson, CL
Beare, PA
Ge, H
Singh, S
Rodino, KG
Heinzen, RA
Richards, AL
Carlyon, JA
AF VieBrock, Lauren
Evans, Sean M.
Beyer, Andrea R.
Larson, Charles L.
Beare, Paul A.
Ge, Hong
Singh, Smita
Rodino, Kyle G.
Heinzen, Robert A.
Richards, Allen L.
Carlyon, Jason A.
TI Orientia tsutsugamushi ankyrin repeat-containing protein family members
are Type 1 secretion system substrates that traffic to the host cell
endoplasrnic reticulum
SO FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
LA English
DT Article
DE Rickettsia; intracellular bacteria; bacterial effector; scrub typhus;
ankyrin repeat; bacterial secretion; ER-tropic effector; secretory
pathway
ID ANAPLASMA-PHAGOCYTOPHILUM ANKA; ESCHERICHIA-COLI HEMOLYSIN;
LEGIONELLA-PNEUMOPHILA; COXIELLA-BURNETII; TRANSPORT SIGNAL; EFFECTOR
PROTEIN; SCRUB TYPHUS; DOMAINS; IDENTIFICATION; PROLIFERATION
AB Scrub typhus is an understudied, potentially fatal infection that threatens one billion persons in the Asia-Pacific region. How the causative obligate intracellular bacterium, Orientia tsutsugamushi, facilitates its intracellular survival and pathogenesis is poorly understood. Many intracellular bacterial pathogens utilize the Type 1 (T1SS) or Type 4 secretion system (T4SS) to translocate ankyrin repeat-containing proteins (Anks) that traffic to distinct subcellular locations and modulate host cell processes. The O. tsutsugamushi genome encodes one of the largest known bacterial Ank repertoires plus T1SS and T4SS components. Whether these potential virulence factors are expressed during infection, how the Anks are potentially secreted, and to where they localize in the host cell are not known. We determined that O. tsutsugamushi transcriptionally expresses 20 unique ank genes as well as genes for both T1SS and T4SS during infection of mammalian host cells. Examination of the Anks' C-termini revealed that the majority of them resemble T1SS substrates. Escherichia colt expressing a functional T1SS was able to secrete chimeric hemolysin proteins bearing the C-termini of 19 of 20 O. tsutsugamushi Anks in an HlyBD-dependent manner. Thus, O. tsutsugamushi Anks C-termini are T1SS-compatible. Conversely, Coxiella burnetii could not secrete heterologously expressed Anks in a T4SS-dependent manner. Analysis of the subcellular distribution patterns of 20 ectopically expressed Anks revealed that, while 6 remained cytosolic or trafficked to the nucleus, 14 localized to, and in some cases, altered the morphology of the endoplasmic reticulum. This study identifies O. tsutsugamushi Anks as T1SS substrates and indicates that many display a tropism for the host cell secretory pathway.
C1 [VieBrock, Lauren; Evans, Sean M.; Beyer, Andrea R.; Singh, Smita; Rodino, Kyle G.; Carlyon, Jason A.] Virginia Commonwealth Univ, Dept Microbiol & Immunol, Sch Med, Richmond, VA 23298 USA.
[Larson, Charles L.; Beare, Paul A.; Heinzen, Robert A.] NIAID, Coxiella Pathogenesis Sect, Rocky Mt Labs, NIH, Hamilton, MT USA.
[Ge, Hong; Richards, Allen L.] Naval Med Res Ctr, Viral & Rickettsial Dis Dept, Silver Spring, MD USA.
RP Carlyon, JA (reprint author), Virginia Commonwealth Univ, Dept Microbiol & Immunol, Sch Med, POB 980678, Richmond, VA 23298 USA.
EM jacarlyon@vcu.edu
FU National Institutes of Health [R03 AI101666, R21 AI103606]; American
Heart Association (AHA) [13GRNT16810009]; AHA Predoctoral Fellowship
[13PRE16840032]; Military Infectious Diseases Research Program
[6000.RAD1.J.A0310]; Virginia Commonwealth University (VCU) Presidential
Research Quest Fund; VCU Institutional Research and Academic Career
Development Award [K12 GM093857]; NIH-NINDS Center core grant
[5P30NS047463]
FX We gratefully acknowledge Peter Sebo (Institute of Microbiology,
Institute of Biotechnology, Academy of Sciences of the Czech Republic,
Prague, Czech Republic) for providing plasmid pLG575, E. coli strain A0
34/86, and many helpful discussions. We thank Rodney Welch (University
of Wisconsin, Madison, WI) for providing the HlyA antibody G3, and Marci
Scidmore of Cornell University (Ithaca, NY) for providing the pEGFP-C1
vector. This work was supported by National Institutes of Health grants
R03 AI101666 and R21 AI103606 (to Jason A. Carlyon), American Heart
Association (AHA) Grant-in-Aid 13GRNT16810009 (to Jason A. Carlyon), AHA
Predoctoral Fellowship 13PRE16840032 (to Lauren VieBrock), Military
Infectious Diseases Research Program 6000.RAD1.J.A0310 (to Hong Ge and
Allen L. Richards), and the Virginia Commonwealth University (VCU)
Presidential Research Quest Fund (to Jason A. Carlyon). Andrea R. Beyer
is a fellowship recipient supported by VCU Institutional Research and
Academic Career Development Award grant K12 GM093857. LSCM was performed
at the VCU Department of Anatomy and Neurobiology Microscopy Facility,
which is supported in part by funding from NIH-NINDS Center core grant
5P30NS047463.
NR 70
TC 4
Z9 4
U1 0
U2 0
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015,
SWITZERLAND
SN 2235-2988
J9 FRONT CELL INFECT MI
JI Front. Cell. Infect. Microbiol.
PD FEB 3
PY 2015
VL 4
AR 186
DI 10.3389/fcimb.2014.00186
PG 20
WC Immunology; Microbiology
SC Immunology; Microbiology
GA CA8HQ
UT WOS:000349159300001
PM 25692099
ER
PT J
AU Papaneri, AB
Bernbaum, JG
Blaney, JE
Jahrling, PB
Schnell, MJ
Johnson, RF
AF Papaneri, Amy B.
Bernbaum, John G.
Blaney, Joseph E.
Jahrling, Peter B.
Schnell, Matthias J.
Johnson, Reed F.
TI Controlled viral glycoprotein expression as a safety feature in a
bivalent rabies-ebola vaccine
SO VIRUS RESEARCH
LA English
DT Article
DE Filovirus; Vaccine; Rabies virus; Ebola; RNA viruses; Biodefense
ID VIRUS GLYCOPROTEIN; ENTRY; PATHOGENICITY; IMMUNIZATION; REPLICATION;
PROTECTION; ANTIBODIES; SEQUENCE; VECTORS; PROTEIN
AB Using a recombinant rabies (RABV) vaccine platform, we have developed several safe and effective vaccines. Most recently, we have developed a RABV-based ebolavirus (EBOV) vaccine that is efficacious in nonhuman primates. One safety feature of this vaccine is the utilization of a live but replication-deficient RABV construct. In this construct, the RABV glycoprotein (G) has been deleted from the genome, requiring G trans complementation in order for new infectious viruses to be released from the initial infected cell. Here we analyze this safety feature of the bivalent RABV-based EBOV vaccine comprised of the G-deleted RABV backbone expressing EBOV glycoprotein (GP). We found that, while the level of RABV genome in infected cells is equivalent regardless of G supplementation, the production of infectious virus is indeed restricted by the lack of G, and most importantly, that the presence of EBOV GP does not substitute for G. These findings further support the safety profile of this replication-deficient RABV-EBOV bivalent vaccine. Published by Elsevier B.V.
C1 [Papaneri, Amy B.; Bernbaum, John G.; Blaney, Joseph E.; Jahrling, Peter B.; Schnell, Matthias J.; Johnson, Reed F.] NIAID, NIH, Ft Detrick, MD USA.
RP Johnson, RF (reprint author), NIAID, NIH, Ft Detrick, MD USA.
EM johnsonreed@mail.nih.gov
OI Papaneri, Amy/0000-0003-2144-2441
FU NIAID Division of Intramural Research; NIAID Division of Clinical
Research; Battelle Memorial Institute; US National Institute of Allergy
and Infectious Diseases (NIAID) Division of Clinical Research
[HHSN272200700016I]
FX This work was supported by the NIAID Division of Intramural Research and
in part by the NIAID Division of Clinical Research. The content of this
publication does not necessarily reflect the views or policies of the US
Department of Health and Human Services (DHHS) or of the institutions
and companies affiliated with the authors. This work was funded in part
through Battelle Memorial Institute's prime contract with the US
National Institute of Allergy and Infectious Diseases (NIAID) Division
of Clinical Research under Contract No. HHSN272200700016I. The
subcontractor to Battelle Memorial Institute who performed this work
was: J.G.B. an employee of Tunnell Government Services, Inc. We would
like to thank Dr. Owen Schwartz, NIAID/DIR/RTB/BIS, for technical
assistance with the Leica TCS SP5 Confocal microscope. We also thank
Jiro Wada, NIAID/DCR/OCSIRFF, for his technical assistance in preparing
the figures for publication.
NR 31
TC 1
Z9 1
U1 1
U2 10
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0168-1702
EI 1872-7492
J9 VIRUS RES
JI Virus Res.
PD FEB 2
PY 2015
VL 197
BP 54
EP 58
DI 10.1016/j.virusres.2014.11.028
PG 5
WC Virology
SC Virology
GA CC7AI
UT WOS:000350519700008
PM 25481284
ER
PT J
AU McMahon, GM
Hwang, SJ
Tanner, RM
Jacques, PF
Selhub, J
Muntner, P
Fox, CS
AF McMahon, Gearoid M.
Hwang, Shih-Jen
Tanner, Rikki M.
Jacques, Paul F.
Selhub, Jacob
Muntner, Paul
Fox, Caroline S.
TI The association between vitamin B12, albuminuria and reduced kidney
function: an observational cohort study
SO BMC NEPHROLOGY
LA English
DT Article
DE Homocysteine; Albuminuria; Vitamin B12; Reduced kidney function
ID RANDOMIZED CONTROLLED-TRIAL; FOLATE; DEFICIENCY; PATHOPHYSIOLOGY;
HEMODIALYSIS; METABOLISM; DISEASE; BLOOD
AB Background: Variants in CUBN, the gene encoding cubilin, a proximal tubular transport protein, have been associated with albuminuria and vitamin B12 (B12) deficiency. We hypothesized that low levels of B12 would be associated with albuminuria in a population-based cohort.
Methods: We analyzed participants from the Framingham Heart Study (n = 2965, mean age 58 years, 53% female) who provided samples for plasma B12. Logistic regression models adjusted for covariates including homocysteine were constructed to test the association between B12 and prevalent albuminuria (UACR >= 17 mg/g [ men] and >= 25 mg/g [women]) and reduced kidney function (defined as an eGFR < 60 ml/min/1.73 m(2), RKF). Because of a significant interaction between B12 and homocysteine in the prevalent RKF model (p = 0.005), the model was stratified by the median homocysteine levels. Logistic regression models were constructed to test the association between B12 and incident albuminuria and RKF. The results were replicated in 4445 participants from NHANES 2003-2004.
Results: Baseline B12 levels ranged from 50-1690 pg/ml. Elevated B12 was associated with prevalent albuminuria (OR 1.44 per 1 SD increase, 95% CI 1.10-1.87) and RKF (OR 1.83, 95% CI 1.30-2.60). However after stratifying by median homocysteine levels, this relationship remained only in the higher homocysteine stratum. There was no association between B12 and incident albuminuria (OR 1.17, 95% CI 0.79 - 1.73) or RKF (OR 1.45, 95% CI 0.97 - 1.88). In the NHANES cohort, elevated B12 was associated with RKF after full covariate adjustment (OR 3.06, 95% CI 2.30-4.08). There was no association with albuminuria.
Conclusion: In participants with high baseline homocysteine levels, increased plasma B12 was associated with RKF.
C1 [McMahon, Gearoid M.; Hwang, Shih-Jen; Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA.
[McMahon, Gearoid M.; Hwang, Shih-Jen; Fox, Caroline S.] Ctr Populat Studies, Framingham, MA 01702 USA.
[McMahon, Gearoid M.; Fox, Caroline S.] Brigham & Womens Hosp, Div Renal, Boston, MA 02115 USA.
[McMahon, Gearoid M.; Fox, Caroline S.] Harvard Univ, Sch Med, Boston, MA USA.
[Tanner, Rikki M.; Muntner, Paul] Univ Alabama Birmingham, Dept Epidemiol, Birmingham, AL USA.
[Jacques, Paul F.; Selhub, Jacob] Tufts Univ, USDA, Human Nutr Ctr Aging, Boston, MA 02111 USA.
[Fox, Caroline S.] Brigham & Womens Hosp, Div Endocrinol, Boston, MA 02115 USA.
RP Fox, CS (reprint author), NHLBI, Framingham Heart Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA.
EM foxca@nhlbi.nih.gov
OI McMahon, Gearoid/0000-0002-7723-2198
FU USDA [58-1950-0-014]; [N01-HC-25195]
FX The Framingham Heart Study of the National Heart, Lung and Blood
Institute is supported by contract N01-HC-25195. Drs. Selhub and Jacques
are supported by USDA agreement No. 58-1950-0-014. The funding bodies
played no role in the study design, analysis or interpretation of data,
writing the manuscript or the decision to submit for publication.
NR 25
TC 0
Z9 0
U1 0
U2 3
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2369
J9 BMC NEPHROL
JI BMC Nephrol.
PD FEB 2
PY 2015
VL 16
AR 16
DI 10.1186/1471-2369-16-7
PG 8
WC Urology & Nephrology
SC Urology & Nephrology
GA CC4ID
UT WOS:000350316000001
ER
PT J
AU Gounden, V
Sacks, DB
Zhao, Z
AF Gounden, Verena
Sacks, David B.
Zhao, Zhen
TI Interference of cerebrospinal fluid total protein measurement by
povidone-iodine contamination
SO CLINICA CHIMICA ACTA
LA English
DT Article
DE Cerebrospinal fluid; Total protein; Pre-analytical interference;
Povidone; Iodine
AB Background: A falsely high cerebrospinal fluid (CSF) total protein (TP) result measured by pyrogallol red (PGR) method was suspected to be caused by preparation of the collection site with povidone-iodine (PVP-iodine) solution.
Methods: CSF TP was evaluated for interference in samples with different final concentrations of PVP-iodine (up to 0.25% PVP and 0.025% iodine) or iodine alone (up to 0.025% iodine) using three methods: PGR, modified biuret and benzethonium chloride (BZTC). Interference exceeding +/- 20% of the baseline value is considered clinically significant according to the criterion defined by the College of American Pathologists.
Results: There were positive interference with the PGR method and negative inference for the BZTC method in CSF samples spiked with PVP-iodine. The PVP-iodine (up to 0.25% PVP and 0.025% iodine) did not cause a clinically significant interference with the modified biuret method. PVP alone without iodine caused a positive interference with the PGR method but did not interfere with the modified biuret or the BZTC method. When the samples were spiked with iodine alone, none of the three methods was affected (change <20%) by iodine concentration up to 0.025%.
Conclusions: Contamination of CSF specimens with PVP-iodine can lead to interference with CSF TP measurements using PGR or BZTC methods. Published by Elsevier B.V.
C1 [Gounden, Verena; Sacks, David B.; Zhao, Zhen] NIH, Ctr Clin, Dept Lab Med, Bethesda, MD 20892 USA.
RP Gounden, V (reprint author), NIH, Ctr Clin, Dept Lab Med, Bldg 10,Room 2C-306, Bethesda, MD 20892 USA.
EM zhen.zhao@nih.gov
OI Sacks, David/0000-0003-3100-0735
FU Intramural Research Program of the National Institutes of Health
FX This research was supported by the Intramural Research Program of the
National Institutes of Health.
NR 2
TC 0
Z9 0
U1 0
U2 4
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 FEB 2
PY 2015
VL 440
BP 3
EP 5
DI 10.1016/j.cca.2014.10.008
PG 3
WC Medical Laboratory Technology
SC Medical Laboratory Technology
GA CB4BT
UT WOS:000349573900002
PM 25446880
ER
PT J
AU Folco, HD
Campbell, CS
May, KM
Espinoza, CA
Oegema, K
Hardwick, KG
Grewal, SIS
Desai, A
AF Folco, H. Diego
Campbell, Christopher S.
May, Karen M.
Espinoza, Celso A.
Oegema, Karen
Hardwick, Kevin G.
Grewal, Shiv I. S.
Desai, Arshad
TI The CENP-A N-Tail Confers Epigenetic Stability to Centromeres via the
CENP-T Branch of the CCAN in Fission Yeast
SO CURRENT BIOLOGY
LA English
DT Article
ID HISTONE FOLD DOMAIN; CHROMOSOME SEGREGATION; OUTER KINETOCHORE;
CHROMATIN; HETEROCHROMATIN; RECRUITMENT; DISTINCT; PROTEIN; RECOGNITION;
REQUIREMENT
AB In most eukaryotes, centromeres are defined epigenetically by presence of the histone H3 variant CENP-A [1-3]. CENPA-containing chromatin recruits the constitutive centromere-associated network (CCAN) of proteins, which in turn directs assembly of the outer kinetochore to form microtubule attachments and ensure chromosome segregation fidelity [4-6]. Whereas the mechanisms that load CENP-A at centromeres are being elucidated, the functions of its divergent N-terminal tail remain enigmatic [7-12]. Here, we employ the well-studied fission yeast centromere [13-16] to investigate the function of the CENP-A (Cnp1) N-tail. We show that alteration of the N-tail does not affect Cnp1 loading at centromeres, outer kinetochore formation, or spindle checkpoint signaling but nevertheless elevates chromosome loss. N-tail mutants exhibited synthetic lethality with an altered centromeric DNA sequence, with rare survivors harboring chromosomal fusions in which the altered centromere was epigenetically inactivated. Elevated centromere inactivation was also observed for N-tail mutants with unaltered centromeric DNA sequences. N-tail mutants specifically reduced localization of the CCAN proteins Cnp20/CENP-T and Mis6/CENP-I, but not Cnp3/CENP-C. Overexpression of Cnp20/CENP-T suppressed defects in an N-tail mutant, suggesting a link between reduced CENP-T recruitment and the observed centromere inactivation phenotype. Thus, the Cnp1 N-tail promotes epigenetic stability of centromeres in fission yeast, at least in part via recruitment of the CENP-T branch of the CCAN.
C1 [Folco, H. Diego; Campbell, Christopher S.; Espinoza, Celso A.; Oegema, Karen; Desai, Arshad] Univ Calif San Diego, Ludwig Inst Canc Res, Dept Cellular & Mol Med, La Jolla, CA 92093 USA.
[May, Karen M.; Hardwick, Kevin G.] Univ Edinburgh, Sch Biol Sci, Inst Cell Biol, Wellcome Trust Ctr Cell Biol, Edinburgh EH9 3BF, Midlothian, Scotland.
[Folco, H. Diego; Grewal, Shiv I. S.] NCI, Lab Biochem & Mol Biol, NIH, Bethesda, MD 20892 USA.
RP Desai, A (reprint author), Univ Calif San Diego, Ludwig Inst Canc Res, Dept Cellular & Mol Med, La Jolla, CA 92093 USA.
EM abdesai@ucsd.edu
OI Hardwick, Kevin/0000-0002-6462-1047
FU NIH [GM074215]; NIH; Wellcome Trust [083610]; Wellcome Trust Centre for
Cell Biology [092076]; NIH/NCI [T32 CA009523-27S1]; Ludwig Institute for
Cancer Research
FX We thank Shigeaki Saitoh and Kohta Takahashi (Kurume University); Alison
Pidoux, Georgina Hamilton, and Robin Allshire (University of Edinburgh);
Takeshi Sakuno and Yoshinori Watanabe (University of Tokyo); Oliver
Limbo and Paul Russell (Scripps Institute); and the National BioResource
Project - Yeast (Japan) for their generosity in sharing strains,
plasmid, and expertise. We thank Bing Ren for supporting acquisition of
the ChIP-seq data sets and Peter Svensson and Karl Ekwall (Karolinska
Institute) and Ben Black and colleagues (University of Pennsylvania) for
communicating unpublished results. This work was supported by NIH grant
GM074215 to A.D. and the Intramural Research Program of the NIH to
S.I.S.G. K.G.H. and K.M.M. were supported by a Wellcome Trust Programme
Grant to K.G.H. (083610) and Wellcome Trust Centre for Cell Biology core
grant 092076. C.A.E. was supported by NIH/NCI training grant T32
CA009523-27S1. A.D. and K.O. receive salary and other support from the
Ludwig Institute for Cancer Research.
NR 38
TC 10
Z9 10
U1 0
U2 6
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 FEB 2
PY 2015
VL 25
IS 3
BP 348
EP 356
DI 10.1016/j.cub.2014.11.060
PG 9
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA CA5SB
UT WOS:000348967000023
PM 25619765
ER
PT J
AU Castilho, JL
Luz, PM
Shepherd, BE
Turner, M
Ribeiro, SR
Bebawy, SS
Netto, JS
McGowan, CC
Veloso, VG
Engels, EA
Sterling, TR
Grinsztejn, B
AF Castilho, Jessica L.
Luz, Paula M.
Shepherd, Bryan E.
Turner, Megan
Ribeiro, Sayonara R.
Bebawy, Sally S.
Netto, Juliana S.
McGowan, Catherine C.
Veloso, Valdilea G.
Engels, Eric A.
Sterling, Timothy R.
Grinsztejn, Beatriz
TI HIV and cancer: a comparative retrospective study of Brazilian and US
clinical cohorts
SO INFECTIOUS AGENTS AND CANCER
LA English
DT Review
DE HIV; Malignancy; Cancer; Brazil; Anal cancer; Kaposi sarcoma;
Non-Hodgkin lymphoma; Lung cancer; Age; Sex
ID HUMAN-IMMUNODEFICIENCY-VIRUS; AIDS-DEFINING MALIGNANCIES; ACTIVE
ANTIRETROVIRAL THERAPY; INFECTED PATIENTS; KAPOSIS-SARCOMA;
CERVICAL-CANCER; UNITED-STATES; HAART ERA; DEATH; RISK
AB Background: With successful antiretroviral therapy, non-communicable diseases, including malignancies, are increasingly contributing to morbidity and mortality among HIV-infected persons. The epidemiology of AIDS-defining cancers (ADCs) and non-AIDS-defining cancers (NADCs) in HIV-infected populations in Brazil has not been well described. It is not known if cancer trends in HIV-infected populations in Brazil are similar to those of other countries where antiretroviral therapy is also widely available.
Methods: We performed a retrospective analysis of clinical cohorts at Instituto Nacional de Infectologia Evandro Chagas (INI) in Rio de Janeiro and Vanderbilt Comprehensive Care Clinic (VCCC) in Nashville from 1998 to 2010. We used Poisson regression and standardized incidence ratios (SIRs) to examine incidence trends. Clinical and demographic predictors of ADCs and NADCs were examined using Cox proportional hazards models.
Results: This study included 2,925 patients at INI and 3,927 patients at VCCC. There were 57 ADCs at INI (65% Kaposi sarcoma), 47 at VCCC (40% Kaposi sarcoma), 45 NADCs at INI, and 82 at VCCC. From 1998 to 2004, incidence of ADCs remained statistically unchanged at both sites. From 2005 to 2010, ADC incidence decreased in both cohorts (INI incidence rate ratio per year = 0.74, p < 0.01; VCCC = 0.75, p < 0.01). Overall Kaposi sarcoma incidence was greater at INI than VCCC (3.0 vs. 1.2 cases per 1,000 person-years, p < 0.01). Incidence of NADCs remained constant throughout the study period (overall INI incidence 3.6 per 1,000 person-years and VCCC incidence 5.3 per 1,000 person-years). Compared to general populations, overall risk of NADCs was increased at both sites (INI SIR = 1.4 [95% CI 1.1-1.9] and VCCC SIR = 1.3 [ 1.0-1.7]). After non-melanoma skin cancers, the most frequent NADCs were anal cancer at INI (n = 7) and lung cancer at VCCC (n = 11). In multivariate models, risk of ADC was associated with male sex and immunosuppression. Risk of NADC was associated with increased age.
Conclusions: In both cohorts, ADCs have decreased over time, though incidence of KS was higher at INI than VCCC. Rates of NADCs remained constant over time at both sites.
C1 [Castilho, Jessica L.; Turner, Megan; Bebawy, Sally S.; McGowan, Catherine C.; Sterling, Timothy R.] Vanderbilt Univ, Sch Med, Div Infect Dis, Dept Med, Nashville, TN 37232 USA.
[Luz, Paula M.; Ribeiro, Sayonara R.; Netto, Juliana S.; Veloso, Valdilea G.; Grinsztejn, Beatriz] HIV AIDS Clin Res Ctr, Inst Nacl Infectol Evandro Chagas, Fundacao Oswaldo Cruz, BR-21040360 Rio De Janeiro, RJ, Brazil.
[Shepherd, Bryan E.] Vanderbilt Univ, Sch Med, Dept Biostat, Nashville, TN 37203 USA.
[Engels, Eric A.] Natl Canc Inst, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
RP Castilho, JL (reprint author), Vanderbilt Univ, Sch Med, Div Infect Dis, Dept Med, MCN A2200,1611 21st Ave South, Nashville, TN 37232 USA.
EM jessica.castilho@vanderbilt.edu
FU National Institutes of Health [T32 AI007474, K24 AI65298, UO1 AI069923];
National Council of Technological and Scientific Development; Research
Agency of the State of Rio de Janeiro; Intramural Research Program of
the National Cancer Institute
FX We are grateful to individuals at INI and VCCC who made this study
possible. We thank Dan Rasbach, and Sam Stinnette at Vanderbilt for
their work abstracting and validating the cancer diagnoses at VCCC. This
study was the result of an INI-Vanderbilt partnership developed through
the Caribbean, Central and South American network for HIV epidemiology
(CCASAnet) study, a multisite HIV cohort study in which INI participates
and Vanderbilt coordinates. We thank CCASAnet data manager Karu
Jayathilake for his statistical assistance in this project. This project
was funded by grants from the National Institutes of Health (T32
AI007474 [JLC], K24 AI65298 [TRS, SSB, MT], UO1 AI069923 [JLC, PML, BES,
CCM, VGV, BG]), the National Council of Technological and Scientific
Development (PML, BG), and the Research Agency of the State of Rio de
Janeiro (PML, BG). Eric Engels was supported by the Intramural Research
Program of the National Cancer Institute.
NR 36
TC 2
Z9 2
U1 0
U2 6
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1750-9378
J9 INFECT AGENTS CANCER
JI Infect. Agents Cancer
PD FEB 2
PY 2015
VL 10
AR 4
DI 10.1186/1750-9378-10-4
PG 10
WC Oncology; Immunology
SC Oncology; Immunology
GA CA8RN
UT WOS:000349188700001
PM 25685180
ER
PT J
AU Artym, VV
Swatkoski, S
Matsumoto, K
Campbell, CB
Petrie, RJ
Dimitriadis, EK
Li, X
Mueller, SC
Bugge, TH
Gucek, M
Yamada, KM
AF Artym, Vira V.
Swatkoski, Stephen
Matsumoto, Kazue
Campbell, Catherine B.
Petrie, Ryan J.
Dimitriadis, Emilios K.
Li, Xin
Mueller, Susette C.
Bugge, Thomas H.
Gucek, Marian
Yamada, Kenneth M.
TI Dense fibrillar collagen is a potent inducer of invadopodia via a
specific signaling network
SO JOURNAL OF CELL BIOLOGY
LA English
DT Article
ID BREAST-CARCINOMA CELLS; I COLLAGEN; EXTRACELLULAR-MATRIX;
PHOSPHORYLATION SITES; ACTIN POLYMERIZATION; CANCER PROGRESSION;
STATISTICAL-MODEL; BASEMENT-MEMBRANE; GENE-EXPRESSION; INTEGRIN
AB Cell interactions with the extracellular matrix (ECM) can regulate multiple cellular activities and the matrix itself in dynamic, bidirectional processes. One such process is local proteolytic modification of the ECM. Invadopodia of tumor cells are actin-rich proteolytic protrusions that locally degrade matrix molecules and mediate invasion. We report that a novel high-density fibrillar collagen (HDFC) matrix is a potent inducer of invadopodia, both in carcinoma cell lines and in primary human fibroblasts. In carcinoma cells, HDFC matrix induced formation of invadopodia via a specific integrin signaling pathway that did not require growth factors or even altered gene and protein expression. In contrast, phosphoproteomics identified major changes in a complex phosphosignaling network with kindlin2 serine phosphorylation as a key regulatory element. This kindlin2-dependent signal transduction network was required for efficient induction of invadopodia on dense fibrillar collagen and for local degradation of collagen. This novel phosphosignaling mechanism regulates cell surface invadopodia via kindlin2 for local proteolytic remodeling of the ECM.
C1 [Artym, Vira V.; Matsumoto, Kazue; Campbell, Catherine B.; Petrie, Ryan J.; Yamada, Kenneth M.] Natl Inst Dent & Craniofacial Res, Lab Cell & Dev Biol, NIH, Bethesda, MD 20892 USA.
[Swatkoski, Stephen; Gucek, Marian] NHLBI, Prote Core Facil, NIH, Bethesda, MD 20892 USA.
[Dimitriadis, Emilios K.] Natl Inst Biomol Imaging & Bioengn, Biomol Engn & Phys Sci Shared Resource Program, NIH, Bethesda, MD 20892 USA.
[Bugge, Thomas H.] Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA.
[Artym, Vira V.; Mueller, Susette C.] Georgetown Univ, Sch Med, Lombardi Comprehens Canc Ctr, Dept Oncol, Washington, DC 20057 USA.
[Li, Xin] Georgetown Univ, Dept Biostat Bioinformat & Biomath, Washington, DC 20057 USA.
RP Artym, VV (reprint author), Natl Inst Dent & Craniofacial Res, Lab Cell & Dev Biol, NIH, Bethesda, MD 20892 USA.
EM vartym@mail.nih.gov; kyamada@dir.nidcr.nih.gov
FU Pathway to Independence Award from National Cancer Institute
[K99CA129205]; American Recovery and Reinvestment Act of 2009 award;
National Institutes of Health/National Institute of Dental and
Craniofacial Research Intramural project [ZIA DE 000719]
FX This work was supported by Pathway to Independence Award K99CA129205
from National Cancer Institute with American Recovery and Reinvestment
Act of 2009 award to V.V. Artym and National Institutes of
Health/National Institute of Dental and Craniofacial Research Intramural
project ZIA DE 000719 to K.M. Yamada.
NR 93
TC 15
Z9 15
U1 3
U2 12
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 950 THIRD AVE, 2ND FLR, NEW YORK, NY 10022 USA
SN 0021-9525
EI 1540-8140
J9 J CELL BIOL
JI J. Cell Biol.
PD FEB 2
PY 2015
VL 208
IS 3
BP 331
EP 350
DI 10.1083/jcb.201405099
PG 20
WC Cell Biology
SC Cell Biology
GA CA5TZ
UT WOS:000348972000007
PM 25646088
ER
PT J
AU Chen, SL
Lee, SY
Chang, YH
Wang, TY
Chen, SH
Chu, CH
Chen, PS
Yang, YK
Hong, JS
Lu, RB
AF Chen, Shiou-Lan
Lee, Sheng-Yu
Chang, Yun-Hsuan
Wang, Tzu-Yun
Chen, Shih-Heng
Chu, Chun-Hsien
Chen, Po See
Yang, Yen Kuang
Hong, Jau-Shyong
Lu, Ru-Band
TI The BDNF Val66Met polymorphism and plasma brain-derived neurotrophic
factor levels in Han Chinese heroin-dependent patients
SO SCIENTIFIC REPORTS
LA English
DT Article
ID ALZHEIMERS-DISEASE; SERUM CONCENTRATIONS; RAT-BRAIN; NEURONS;
SCHIZOPHRENIA; METAANALYSIS; ADDICTION; RECEPTORS; PLATELETS; MEMORY
AB BDNF and its gene polymorphism may be important in synaptic plasticity and neuron survival, and may become a key target in the physiopathology of long-term heroin use. Thus, we investigated the relationships between brain-derived neurotrophic factor (BDNF) plasma concentrations and the BDNF Val66Met nucleotide polymorphism (SNP) in heroin-dependent patients. The pretreatment expression levels of plasma BDNF and the BDNF Val66Met SNP in 172 heroin-dependent patients and 102 healthy controls were checked. BDNF levels were significantly lower in patients (F = 52.28, p < 0.0001), but the distribution of the SNP was not significantly different. Nor were plasma BDNF levels significantly different between Met/Met, Met/Val, and Val/Val carriers in each group, which indicated that the BDNF Val66Met SNP did not affect plasma BDNF levels in our participants. In heroin-dependent patients, plasma BDNF levels were negatively correlated with the length of heroin dependency. Long-term (>15 years) users had significantly lower plasma BDNF levels than did short-term (<5 years) users. We conclude that plasma BDNF concentration in habitual heroin users are not affected by BDNF Val66Met gene variants, but by the length of the heroin dependency.
C1 [Chen, Shiou-Lan] Kaohsiung Med Univ, Sch Med, Dept Neurol, Kaohsiung, Taiwan.
[Lu, Ru-Band] Natl Cheng Kung Univ, Inst Behav Med, Tainan 70101, Taiwan.
[Chang, Yun-Hsuan; Wang, Tzu-Yun; Chen, Po See; Yang, Yen Kuang; Lu, Ru-Band] Natl Cheng Kung Univ, Dept Psychiat, Tainan 70101, Taiwan.
[Lu, Ru-Band] Natl Cheng Kung Univ, Coll Med, Inst Allied Hlth Sci, Tainan 70101, Taiwan.
[Lu, Ru-Band] Natl Cheng Kung Univ, Addict Res Ctr, Tainan 70101, Taiwan.
[Lu, Ru-Band] Natl Hlth Res Inst, Ctr Neuropsychiat Res, Tainan, Taiwan.
[Lee, Sheng-Yu] Kaohsiung Vet Gen Hosp, Dept Psychiat, Kaohsiung, Taiwan.
[Chen, Shih-Heng; Chu, Chun-Hsien; Hong, Jau-Shyong] NIEHS, Neuropharmacol Sect, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC USA.
RP Lu, RB (reprint author), Natl Cheng Kung Univ, Inst Behav Med, Tainan 70101, Taiwan.
EM rblu@mail.ncku.edu.tw
FU Taiwan National Science Council [NSC98-2314-B-006-022-MY3,
NSC101-2314-B-006-063-MY3]; National Cheng Kung University Project to
Promote Academic Excellence and Develop a World Class Research Center
FX This study was supported in part by grants NSC98-2314-B-006-022-MY3 (to
RBL) and NSC101-2314-B-006-063-MY3 (to RBL) from the Taiwan National
Science Council, and by a grant from the National Cheng Kung University
Project to Promote Academic Excellence and Develop a World Class
Research Center.
NR 37
TC 2
Z9 3
U1 1
U2 11
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD FEB 2
PY 2015
VL 5
AR 8148
DI 10.1038/srep08148
PG 6
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CA1JW
UT WOS:000348669900001
PM 25640280
ER
PT J
AU Wang, Z
Yu, DZ
Wang, MQ
Wang, QL
Kouznetsova, J
Yang, RZ
Qian, K
Wu, WJ
Shuldiner, A
Sztalryd, C
Zou, MH
Zheng, W
Gong, DW
AF Wang, Zhi
Yu, Daozhan
Wang, Mengqiao
Wang, Qilong
Kouznetsova, Jennifer
Yang, Rongze
Qian, Kun
Wu, Wenjun
Shuldiner, Alan
Sztalryd, Carole
Zou, Minghui
Zheng, Wei
Gong, Da-Wei
TI Elabela-Apelin Receptor Signaling Pathway is Functional in Mammalian
Systems
SO SCIENTIFIC REPORTS
LA English
DT Article
ID ENDOGENOUS LIGAND APELIN; NITRIC-OXIDE SYNTHASE; IN-VIVO; CARDIAC
CONTRACTILITY; FLUID HOMEOSTASIS; ORPHAN RECEPTOR; BLOOD-PRESSURE; APJ
RECEPTOR; KINASE; ACTIVATION
AB Elabela (ELA) or Toddler is a recently discovered hormone which is required for normal development of heart and vasculature through activation of apelin receptor (APJ), a G protein-coupled receptor (GPCR), in zebrafish. The present study explores whether the ELA-APJ signaling pathway is functional in the mammalian system. Using reverse-transcription PCR, we found that ELA is restrictedly expressed in human pluripotent stem cells and adult kidney whereas APJ is more widely expressed. We next studied ELA-APJ signaling pathway in reconstituted mammalian cell systems. Addition of ELA to HEK293 cells over-expressing GFP-AJP fusion protein resulted in rapid internalization of the fusion receptor. In Chinese hamster ovarian (CHO) cells over-expressing human APJ, ELA suppresses cAMP production with EC50 of 11.1 nM, stimulates ERK1/2 phosphorylation with EC50 of 14.3 nM and weakly induces intracellular calcium mobilization. Finally, we tested ELA biological function in human umbilical vascular endothelial cells and showed that ELA induces angiogenesis and relaxes mouse aortic blood vessel in a dose-dependent manner through a mechanism different from apelin. Collectively, we demonstrate that the ELA-AJP signaling pathways are functional in mammalian systems, indicating that ELA likely serves as a hormone regulating the circulation system in adulthood as well as in embryonic development.
C1 [Wang, Zhi; Yu, Daozhan; Yang, Rongze; Qian, Kun; Wu, Wenjun; Shuldiner, Alan; Sztalryd, Carole; Gong, Da-Wei] Univ Maryland, Sch Med, Dept Med, Div Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA.
[Wang, Zhi] Southeast Univ, Nanjing Chest Hosp, Dept Cardiol, Sch Med, Nanjing 210029, Jiangsu, Peoples R China.
[Wang, Mengqiao; Kouznetsova, Jennifer; Zheng, Wei] NIH, Natl Ctr Adv Translat Sci, Bethesda, MD 20892 USA.
[Wang, Qilong; Zou, Minghui] Univ Oklahoma, Hlth Sci Ctr, Dept Internal Med, Oklahoma City, OK 73104 USA.
RP Gong, DW (reprint author), Univ Maryland, Sch Med, Dept Med, Div Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA.
EM dgong@medicine.umaryland.edu
RI Zheng, Wei/J-8889-2014; wang, qilong/O-1962-2013
OI Zheng, Wei/0000-0003-1034-0757;
FU Maryland Stem Cell Research Fund; Mid-Atlantic Nutrition Obesity
Research Center [DK072488]; Baltimore Diabetes Research and Training
Center [P60-DK-079637]
FX This work was supported in part by grants from Maryland Stem Cell
Research Fund, the Mid-Atlantic Nutrition Obesity Research Center
(DK072488), and the Baltimore Diabetes Research and Training Center
(P60-DK-079637).
NR 39
TC 11
Z9 11
U1 1
U2 19
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2045-2322
J9 SCI REP-UK
JI Sci Rep
PD FEB 2
PY 2015
VL 5
AR 8170
DI 10.1038/srep08170
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CA1KB
UT WOS:000348670400004
PM 25639753
ER
PT J
AU Repunte-Canonigo, V
Shin, W
Vendruscolo, LF
Lefebvre, C
van der Stap, L
Kawamura, T
Schlosburg, JE
Alvarez, M
Koob, GF
Califano, A
Sanna, PP
AF Repunte-Canonigo, Vez
Shin, William
Vendruscolo, Leandro F.
Lefebvre, Celine
van der Stap, Lena
Kawamura, Tomoya
Schlosburg, Joel E.
Alvarez, Mariano
Koob, George F.
Califano, Andrea
Sanna, Pietro Paolo
TI Identifying candidate drivers of alcohol dependence-induced excessive
drinking by assembly and interrogation of brain-specific regulatory
networks
SO GENOME BIOLOGY
LA English
DT Article
AB Background: A systems biology approach based on the assembly and interrogation of gene regulatory networks, or interactomes, was used to study neuroadaptation processes associated with the transition to alcohol dependence at the molecular level.
Results: Using a rat model of dependent and non-dependent alcohol self-administration, we reverse engineered a global transcriptional regulatory network during protracted abstinence, a period when relapse rates are highest. We then interrogated the network to identify master regulator genes that mechanistically regulate brain region-specific signatures associated with dependent and non-dependent alcohol self-administration. Among these, the gene coding for the glucocorticoid receptor was independently identified as a master regulator in multiple brain regions, including the medial prefrontal cortex, nucleus accumbens, central nucleus of the amygdala, and ventral tegmental area, consistent with the view that brain reward and stress systems are dysregulated during protracted abstinence. Administration of the glucocorticoid antagonist mifepristone in either the nucleus accumbens or ventral tegmental area selectively decreased dependent, excessive, alcohol self-administration in rats but had no effect on non-dependent, moderate, alcohol self-administration.
Conclusions: Our study suggests that assembly and analysis of regulatory networks is an effective strategy for the identification of key regulators of long-term neuroplastic changes within specific brain regions that play a functional role in alcohol dependence. More specifically, our results support a key role for regulatory networks downstream of the glucocorticoid receptor in excessive alcohol drinking during protracted alcohol abstinence.
C1 [Repunte-Canonigo, Vez; van der Stap, Lena; Kawamura, Tomoya; Sanna, Pietro Paolo] Scripps Res Inst, Mol & Integrat Neurosci Dept, La Jolla, CA 92037 USA.
[Vendruscolo, Leandro F.; Schlosburg, Joel E.; Koob, George F.] Scripps Res Inst, Committee Neurobiol Addict Disorders, La Jolla, CA 92037 USA.
[Shin, William] Columbia Univ, Dept Biol Sci, New York, NY 10027 USA.
[Shin, William; Lefebvre, Celine; Alvarez, Mariano; Califano, Andrea] Columbia Univ, Dept Syst Biol, Herbert Irving Comprehens Canc Ctr, New York, NY 10032 USA.
[Califano, Andrea] Columbia Univ, Herbert Irving Comprehens Canc Ctr, Dept Biomed Informat, New York, NY 10032 USA.
[Califano, Andrea] Columbia Univ, Inst Canc Genet, Herbert Irving Comprehens Canc Ctr, New York, NY 10032 USA.
[Califano, Andrea] Columbia Univ, Dept Biochem & Mol Biophys, Hammer Hlth Sci Ctr, New York, NY 10032 USA.
[Califano, Andrea] Columbia Univ, Canc Regulatory Network Program, Herbert Irving Comprehens Canc Ctr, New York, NY 10032 USA.
[Lefebvre, Celine] INSERM, Unit U981, Inst Gustave Roussy, Villejuif, France.
[Vendruscolo, Leandro F.] NIDA, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
[Koob, George F.] NIAAA, Rockville, MD 20852 USA.
[Califano, Andrea] Scripps Res Inst, 10550 North Torrey Pines Rd, La Jolla, CA 92037 USA.
RP Sanna, PP (reprint author), Scripps Res Inst, Mol & Integrat Neurosci Dept, La Jolla, CA 92037 USA.; Califano, A (reprint author), Columbia Univ, Dept Syst Biol, Herbert Irving Comprehens Canc Ctr, New York, NY 10032 USA.; Califano, A (reprint author), Columbia Univ, Herbert Irving Comprehens Canc Ctr, Dept Biomed Informat, New York, NY 10032 USA.; Califano, A (reprint author), Columbia Univ, Inst Canc Genet, Herbert Irving Comprehens Canc Ctr, New York, NY 10032 USA.; Califano, A (reprint author), Columbia Univ, Dept Biochem & Mol Biophys, Hammer Hlth Sci Ctr, New York, NY 10032 USA.; Califano, A (reprint author), Columbia Univ, Canc Regulatory Network Program, Herbert Irving Comprehens Canc Ctr, New York, NY 10032 USA.; Califano, A (reprint author), Scripps Res Inst, 10550 North Torrey Pines Rd, La Jolla, CA 92037 USA.
EM califano@c2b2.columbia.edu; psanna@scripps.edu
RI Lefebvre, Celine/E-6290-2013; koob, george/P-8791-2016
FU NIH [AA017371, AA020960, DA013821, GM085659, AA021667, CA121852-09,
CA1968426, HL111566]
FX Supported by NIH grants AA017371, AA020960, DA013821, GM085659 (PPS);
AA021667 (PPS/AC); CA121852-09, CA1968426, HL111566 (AC). We are
grateful to Dr. Ronald A. Bush of NIH/NIDCD for the AAV expressing Psip1
and control AAV.
NR 50
TC 8
Z9 8
U1 2
U2 4
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1474-760X
J9 GENOME BIOL
JI Genome Biol.
PD FEB 2
PY 2015
VL 16
AR 68
DI 10.1186/s13059-015-0593-5
PG 13
WC Biotechnology & Applied Microbiology; Genetics & Heredity
SC Biotechnology & Applied Microbiology; Genetics & Heredity
GA V45YM
UT WOS:000209851900001
PM 25886852
ER
PT J
AU Muller, TA
Grundler, R
Istvanffy, R
Hennighausen, L
Illert, AL
Duyster, J
AF Mueller, T. A.
Grundler, R.
Istvanffy, R.
Hennighausen, L.
Illert, A. L.
Duyster, J.
TI The Role Of Stat5 in FLT3-Mediated Leukemogenesis
SO ANNALS OF HEMATOLOGY
LA English
DT Meeting Abstract
C1 [Mueller, T. A.; Illert, A. L.; Duyster, J.] Univ Hosp Freiburg, Dept Internal Med 1, Freiburg, Germany.
[Grundler, R.; Istvanffy, R.] Mission Res Inc, Dept Internal Med 3, Munich, Germany.
[Hennighausen, L.] NIDDK, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0939-5555
EI 1432-0584
J9 ANN HEMATOL
JI Ann. Hematol.
PD FEB
PY 2015
VL 94
SU 1
MA 21
BP S80
EP S81
PG 2
WC Hematology
SC Hematology
GA DA0HS
UT WOS:000367478800068
ER
PT J
AU Wertheimer, A
AF Wertheimer, Alan
TI The ethics of promulgating principles of research ethics: the problem of
diversion effects
SO JOURNAL OF LAW AND THE BIOSCIENCES
LA English
DT Article
DE Research ethics; regulation; promulgations; standard of care; incentives
ID CARE
AB There is an important distinction between ethical standards for the conduct of research with human subjects and the ethics of promulgating principles of research ethics. Those who promulgate ethical standards for the conduct of research have an ethical responsibility to consider the consequences to which those promulgations give rise. In particular, they must consider whether their promulgations will give researchers incentives not to conduct research or not to conduct research in locales in which participants would benefit from participation. I first show how such 'diversion effects' are possible and then examine four principles of research ethics in that light. I then consider several objections to the argument that those who promulgate principles of research ethics should consider diversion effects.
C1 [Wertheimer, Alan] Natl Inst Hlth, Ctr Clin, Dept Bioeth, Res Triangle Pk, NC 27709 USA.
RP Wertheimer, A (reprint author), Natl Inst Hlth, Ctr Clin, Dept Bioeth, Res Triangle Pk, NC 27709 USA.
EM wertheimera@cc.nih.gov
NR 38
TC 3
Z9 3
U1 1
U2 1
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 2053-9711
J9 J LAW BIOSCI
JI J. Law Biosci.
PD FEB
PY 2015
VL 2
IS 1
BP 2
EP 32
DI 10.1093/jlb/lsu039
PG 31
WC Law
SC Government & Law
GA CY6HW
UT WOS:000366510800002
ER
PT J
AU Buck, SM
Isaacs, E
Baldeweg, T
Polkey, CE
Mishkin, M
Vargha-Khadem, F
AF Buck, S. M.
Isaacs, E.
Baldeweg, T.
Polkey, C. E.
Mishkin, M.
Vargha-Khadem, F.
TI BETTER POST-OPERATIVE VERBAL LEARNING CAPACITY IN PATIENTS WITH EARLIER
ONSET OF EPILEPSY
SO EPILEPSIA
LA English
DT Meeting Abstract
CT 31st International Epilepsy Congress
CY SEP 05-09, 2015
CL Istanbul, TURKEY
C1 [Buck, S. M.; Baldeweg, T.; Vargha-Khadem, F.] UCL, Inst Child Hlth, Cognit Neurosci & Neuropsychiat, London, England.
[Isaacs, E.] UCL, Inst Child Hlth, MRC, Childhood Nutr Res Ctr, London, England.
[Polkey, C. E.] Kings Coll London, Inst Psychiat, Dept Clin Neurosci, London WC2R 2LS, England.
[Mishkin, M.] NIMH, Neuropsychol Lab, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0013-9580
EI 1528-1167
J9 EPILEPSIA
JI Epilepsia
PD FEB
PY 2015
VL 56
SU 1
SI SI
MA p0295
BP 79
EP 79
PG 1
WC Clinical Neurology
SC Neurosciences & Neurology
GA CX5QG
UT WOS:000365756500231
ER
PT J
AU Dehghani, A
Isaacs, E
Della Rocchetta, AI
Pitts, G
Polkey, CE
Mishkin, M
Vargha-Khadem, F
AF Dehghani, A.
Isaacs, E.
Della Rocchetta, A. I.
Pitts, G.
Polkey, C. E.
Mishkin, M.
Vargha-Khadem, F.
TI MEMORY & LEARNING AFTER TEMPORAL LOBE SURGERY: EFFECTS OF HEMISPHERIC
SIDE AND EXTENT OF SURGICAL REMOVAL
SO EPILEPSIA
LA English
DT Meeting Abstract
CT 31st International Epilepsy Congress
CY SEP 05-09, 2015
CL Istanbul, TURKEY
C1 [Dehghani, A.] BIHE, Biol, Tehran, Iran.
[Isaacs, E.] UCL, Inst Child Hlth, MRC, Childhood Nutr Res Ctr, London, England.
[Della Rocchetta, A. I.] Wellington Hosp, Neuropsychol, London, England.
[Pitts, G.; Vargha-Khadem, F.] UCL, Inst Child Hlth, Sect Cognit Neurosci & Neuropsychiat, London, England.
[Pitts, G.; Vargha-Khadem, F.] Great Ormond St Hosp Sick Children, London WC1N 3JH, England.
[Polkey, C. E.] Kings Coll London, London WC2R 2LS, England.
[Polkey, C. E.] Univ London, London, England.
[Polkey, C. E.] Maudsley Hosp & Inst Psychiat, London SE5 8AZ, England.
[Mishkin, M.] NIMH, Neuropsychol Lab, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0013-9580
EI 1528-1167
J9 EPILEPSIA
JI Epilepsia
PD FEB
PY 2015
VL 56
SU 1
SI SI
MA p0297
BP 80
EP 80
PG 1
WC Clinical Neurology
SC Neurosciences & Neurology
GA CX5QG
UT WOS:000365756500233
ER
PT J
AU Cooper, HA
Najafi, AH
Ghafourian, K
Paixao, ARM
Aljaabari, M
Iantorno, M
Canos, D
Asch, FM
Paza, JA
AF Cooper, Howard A.
Najafi, Amir H.
Ghafourian, Kambiz
Paixao, Andre R. M.
Aljaabari, Mohamed
Iantorno, Micaela
Canos, Daniel
Asch, Federico M.
Paza, Julio A.
TI Diagnosis of cardiogenic shock without the use of a pulmonary artery
catheter
SO EUROPEAN HEART JOURNAL-ACUTE CARDIOVASCULAR CARE
LA English
DT Article
DE Shock; diagnosis; echocardiography
ID RANDOMIZED CONTROLLED-TRIAL; RISK SURGICAL PATIENTS; VASCULAR-SURGERY;
OUTCOMES; MANAGEMENT
AB Background: Current diagnostic criteria for cardiogenic shock (CS) require the use of a pulmonary artery catheter (PAC), which is time-consuming and may cause complications. A set of simple yet accurate noninvasive diagnostic criteria would be of significant utility.
Methods: Candidate components for the Noninvasive Parameters for Assessment of Cardiogenic Shock (N-PACS) criteria were required to be objective, readily available, and noninvasive. Variables encompassing hypotension, hypoperfusion, predisposing conditions, and elevated intracardiac filling pressures were optimized versus a PAC-based standard in a retrospective developmental cohort of 122 patients with acute myocardial infarction (AMI). The finalized criteria were validated in a prospective cohort of coronary care unit patients in whom a PAC was placed for clinical indications.
Results: According to invasive criteria, CS was present in 32 of 217 consecutive patients undergoing PAC. Compared to the PAC-based standard, the N-PACS criteria had a sensitivity of 96.9% (95% confidence interval (CI) 82.0-99.8), specificity of 90.8% (95% CI 85.5-94.4), positive predictive value of 64.6% (95% CI 49.4-77.4), negative predictive value of 99.4% (95% CI 96.2-100), positive likelihood ratio of 10.5 (95% CI 6.7-16.7), negative likelihood ratio of 0.03 (95% CI 0.00-0.24), and diagnostic odds ratio of 306.4. Results were similar among patients with and without AMI.
Conclusion: A simple, echocardiography-based set of noninvasive diagnostic criteria can be used to accurately diagnose CS.
C1 [Cooper, Howard A.; Najafi, Amir H.; Ghafourian, Kambiz; Asch, Federico M.] Medstar Washington Hosp Ctr, MedStar Heart Inst, Washington, DC 20010 USA.
[Paixao, Andre R. M.] Univ Texas, Dept Med, Houston, TX USA.
[Aljaabari, Mohamed] Tufts Univ, Dept Internal Med, Medford, MA USA.
[Iantorno, Micaela] NIH, Dept Crit Care Med, Bethesda, MD USA.
[Canos, Daniel] US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA.
[Paza, Julio A.] New York Med Coll, Westchester Med Ctr, Valhalla, NY 10595 USA.
RP Cooper, HA (reprint author), Medstar Washington Hosp Ctr, 110 Irving St NW,Suite NA-1103, Washington, DC 20010 USA.
EM cooperh@verizon.net
NR 25
TC 1
Z9 1
U1 2
U2 2
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 2048-8726
EI 2048-8734
J9 EUR HEART J-ACUTE CA
JI Eur. Heart J.-Acute Cardiovasc. Care
PD FEB
PY 2015
VL 4
IS 1
BP 88
EP 95
DI 10.1177/2048872614534564
PG 8
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA CW6NW
UT WOS:000365115300013
PM 24833639
ER
PT J
AU Bandara, G
Beaven, MA
Olivera, A
Gilfillan, AM
Metcalfe, DD
AF Bandara, Geethani
Beaven, Michael A.
Olivera, Ana
Gilfillan, Alasdair M.
Metcalfe, Dean D.
TI Activated Mast Cells Produce Soluble ST2, a Decoy Receptor for IL-33
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology
(AAAAI)
CY FEB 20-24, 2015
CL Houston, TX
SP Amer Acad Allergy, Asthma & Immunol
C1 [Bandara, Geethani; Olivera, Ana; Gilfillan, Alasdair M.; Metcalfe, Dean D.] NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA.
[Beaven, Michael A.] NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 FEB
PY 2015
VL 135
IS 2
SU S
MA 206
BP AB64
EP AB64
PG 1
WC Allergy; Immunology
SC Allergy; Immunology
GA CR2BN
UT WOS:000361129600207
ER
PT J
AU Chiang, D
Burks, AW
Davidson, W
Dawson, P
Grishin, A
Henning, A
Jones, SM
Leung, DYM
Lindblad, RW
Liu, AH
Scurlock, AM
Sicherer, SH
Vickery, BP
Wood, RA
Sampson, HA
Berin, C
AF Chiang, David
Burks, A. Wesley
Davidson, Wendy
Dawson, Peter
Grishin, Alexander
Henning, Alice
Jones, Stacie M.
Leung, Donald Y. M.
Lindblad, Robert W.
Liu, Andrew H.
Scurlock, Amy M.
Sicherer, Scott H.
Vickery, Brian P.
Wood, Robert A.
Sampson, Hugh A.
Berin, Cecilia
TI Phenotypic Analysis of Peanut-Responsive T Cells at Baseline in Subjects
Enrolled in CoFAR6, a Randomized Placebo-Controlled Epicutaneous
Immunotherapy (EPIT) Trial for the Treatment of Peanut Allergy
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology
(AAAAI)
CY FEB 20-24, 2015
CL Houston, TX
SP Amer Acad Allergy, Asthma & Immunol
C1 [Chiang, David; Grishin, Alexander; Sicherer, Scott H.; Berin, Cecilia] Icahn Sch Med Mt Sinai, New York, NY 10029 USA.
[Burks, A. Wesley] Univ N Carolina, Chapel Hill, NC USA.
[Davidson, Wendy] NIH, Bethesda, MD 20892 USA.
[Dawson, Peter; Henning, Alice; Lindblad, Robert W.] EMMES Corp, Rockville, MD USA.
[Jones, Stacie M.] Univ Arkansas Med Sci, Little Rock, AR 72205 USA.
[Leung, Donald Y. M.; Liu, Andrew H.] Natl Jewish Hlth, Denver, CO USA.
[Scurlock, Amy M.] UAMS AR Childrens Hosp, Little Rock, AR USA.
[Vickery, Brian P.] Univ N Carolina, Dept Pediat, Chapel Hill, NC USA.
[Wood, Robert A.] Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21205 USA.
[Sampson, Hugh A.] Icahn Sch Med Mt Sinai, Dept Pediat, New York, NY 10029 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
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 FEB
PY 2015
VL 135
IS 2
SU S
MA 731
BP AB226
EP AB226
PG 1
WC Allergy; Immunology
SC Allergy; Immunology
GA CR2BN
UT WOS:000361129600730
ER
PT J
AU Clark, A
Metcalfe, DD
Cantave, D
Scott, LM
Carter, MC
AF Clark, Alicia
Metcalfe, Dean D.
Cantave, Daly
Scott, Linda M.
Carter, Melody C.
TI Adverse Vaccine Reactions in Children with Pediatric Mastocytosis
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology
(AAAAI)
CY FEB 20-24, 2015
CL Houston, TX
SP Amer Acad Allergy, Asthma & Immunol
C1 [Clark, Alicia] NIH, Bethesda, MD 20892 USA.
[Metcalfe, Dean D.; Scott, Linda M.; Carter, Melody C.] NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA.
[Cantave, Daly] NIH, Ctr Clin, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
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 FEB
PY 2015
VL 135
IS 2
SU S
MA 865
BP AB266
EP AB266
PG 1
WC Allergy; Immunology
SC Allergy; Immunology
GA CR2BN
UT WOS:000361129600864
ER
PT J
AU Cruse, G
Beaven, MA
Music, SC
Bradding, P
Metcalfe, DD
AF Cruse, Glenn
Beaven, Michael A.
Music, Stephen C.
Bradding, Peter
Metcalfe, Dean D.
TI The Fceri beta Homologue, MS4A4, Promotes Fc epsilon ri- Dependent Human
Mast Cell Degranulation By Facilitating PLC gamma 1 Signaling
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology
(AAAAI)
CY FEB 20-24, 2015
CL Houston, TX
SP Amer Acad Allergy, Asthma & Immunol
C1 [Cruse, Glenn; Music, Stephen C.; Metcalfe, Dean D.] NHLBI, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA.
[Beaven, Michael A.] NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA.
[Bradding, Peter] Univ Leicester, Leicester, Leics, England.
NR 0
TC 1
Z9 1
U1 1
U2 2
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 FEB
PY 2015
VL 135
IS 2
SU S
MA 775
BP AB240
EP AB240
PG 1
WC Allergy; Immunology
SC Allergy; Immunology
GA CR2BN
UT WOS:000361129600774
ER
PT J
AU Druey, KM
Balenga, N
Xie, ZH
Laviolette, M
Klichinsky, M
Panettieri, RA
Chan, EC
Jude, J
Zhao, M
AF Druey, Kirk M.
Balenga, Nariman
Xie, Zhihui
Laviolette, Michel
Klichinsky, Michael
Panettieri, Reynold A., Jr.
Chan, Eunice C.
Jude, Joseph
Zhao, Ming
TI A Fungal Protease Allergen Provokes Airway Hyperresponsiveness in Asthma
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology
(AAAAI)
CY FEB 20-24, 2015
CL Houston, TX
SP Amer Acad Allergy, Asthma & Immunol
C1 [Druey, Kirk M.] NIAID, NIH, LAD, Bethesda, MD 20892 USA.
[Balenga, Nariman; Xie, Zhihui; Chan, Eunice C.; Zhao, Ming] NIH, Bethesda, MD USA.
[Laviolette, Michel] Ctr Pheum Laval, Ste Foy, PQ, Canada.
[Klichinsky, Michael; Panettieri, Reynold A., Jr.; Jude, Joseph] Univ Penn, Philadelphia, PA 19104 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
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 FEB
PY 2015
VL 135
IS 2
SU S
MA L25
BP AB389
EP AB389
PG 1
WC Allergy; Immunology
SC Allergy; Immunology
GA CR2BN
UT WOS:000361129600944
ER
PT J
AU Gallagher, JL
Eckrich, M
Cohen, J
Patel, NC
AF Gallagher, Joel L.
Eckrich, Michael
Cohen, Jeffrey
Patel, Niraj C.
TI Tubular Interstitial Nephritis, an Unusual Manifestation of T
Cell-Associated Severe Chronic Active Epstein-Barr Virus Infection
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology
(AAAAI)
CY FEB 20-24, 2015
CL Houston, TX
SP Amer Acad Allergy, Asthma & Immunol
C1 [Gallagher, Joel L.] Med Coll Wisconsin, Milwaukee, WI 53226 USA.
[Eckrich, Michael] Levine Childrens Hosp, Charlotte, NC USA.
[Cohen, Jeffrey] NIH, Bethesda, MD 20892 USA.
[Patel, Niraj C.] Carolinas Med Ctr, Levine Childrens Hosp, Charlotte, NC 28203 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 FEB
PY 2015
VL 135
IS 2
SU S
MA 38
BP AB12
EP AB12
PG 1
WC Allergy; Immunology
SC Allergy; Immunology
GA CR2BN
UT WOS:000361129600039
ER
PT J
AU Gorelik, M
Narisety, S
Chichester, K
Guerrerio, A
Bieneman, AP
Keet, C
Hamilton, RG
Wood, RA
Schroeder, JT
Guerrerio, PF
AF Gorelik, Mark
Narisety, Satya
Chichester, Kristin
Guerrerio, Anthony
Bieneman, Anja P.
Keet, Corinne
Hamilton, Robert G.
Wood, Robert A.
Schroeder, John T.
Guerrerio, Pamela Frischmeyer
TI Impact of Sublingual and Oral Immunotherapy for Peanut Allergy on Blood
Dendritic Cells
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology
(AAAAI)
CY FEB 20-24, 2015
CL Houston, TX
SP Amer Acad Allergy, Asthma & Immunol
C1 [Gorelik, Mark] Johns Hopkins Med Inst, Baltimore, MD 21205 USA.
[Narisety, Satya; Chichester, Kristin; Guerrerio, Anthony; Keet, Corinne; Hamilton, Robert G.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
[Bieneman, Anja P.; Schroeder, John T.] Johns Hopkins Univ, Baltimore, MD USA.
[Wood, Robert A.] Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21205 USA.
[Guerrerio, Pamela Frischmeyer] NIAID, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 FEB
PY 2015
VL 135
IS 2
SU S
MA 203
BP AB63
EP AB63
PG 1
WC Allergy; Immunology
SC Allergy; Immunology
GA CR2BN
UT WOS:000361129600204
ER
PT J
AU Green, BJ
Nayak, AP
Croston, TL
Lemons, AR
Marshall, NB
Goldsmith, WT
Kashon, M
Law, BF
Wagner, LM
Long, CM
Germolec, DM
Beezhold, DH
AF Green, Brett J.
Nayak, Ajay P.
Croston, Tara L.
Lemons, Angela R.
Marshall, Nikki B.
Goldsmith, W. Travis
Kashon, Michael
Law, Brandon F.
Wagner, Lauren M.
Long, Carrie M.
Germolec, Dori M.
Beezhold, Donald H.
TI Fungal Viability Is Essential in Modulating of Adaptive Immune Responses
in Mice
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology
(AAAAI)
CY FEB 20-24, 2015
CL Houston, TX
SP Amer Acad Allergy, Asthma & Immunol
C1 [Green, Brett J.; Nayak, Ajay P.; Croston, Tara L.; Lemons, Angela R.; Marshall, Nikki B.; Law, Brandon F.; Wagner, Lauren M.; Long, Carrie M.; Beezhold, Donald H.] NIOSH, CDC, ACIB, Morgantown, WV USA.
[Goldsmith, W. Travis] NIOSH, CDC, PPRB, Morgantown, WV USA.
[Kashon, Michael] NIOSH, CDC, BEB, Morgantown, WV USA.
[Germolec, Dori M.] NIEHS, NTP, Res Triangle Pk, NC 27709 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
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 FEB
PY 2015
VL 135
IS 2
SU S
MA 56
BP AB18
EP AB18
PG 1
WC Allergy; Immunology
SC Allergy; Immunology
GA CR2BN
UT WOS:000361129600057
ER
PT J
AU Happel, CS
Stone, KD
Hickstein, DD
Freeman, AF
Su, HC
AF Happel, Corinne Savides
Stone, Kelly D.
Hickstein, Dennis D.
Freeman, Alexandra F.
Su, Helen C.
TI Persisting Food Allergen Sensitization after Allogeneic Hematopoietic
Stem Cell Transplantation for DOCK8 Deficiency
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology
(AAAAI)
CY FEB 20-24, 2015
CL Houston, TX
SP Amer Acad Allergy, Asthma & Immunol
C1 [Happel, Corinne Savides; Su, Helen C.] NIAID, NIH, Host Def Lab, Bethesda, MD 20892 USA.
[Stone, Kelly D.] NIAID, NIH, Lab Allerg Dis, Bethesda, MD 20892 USA.
[Hickstein, Dennis D.] NCI, NIH, Dept Expt Transplantat & Immunol, Bethesda, MD 20892 USA.
[Freeman, Alexandra F.] NIAID, NIH, Lab Clin Infect Dis, Bethesda, MD 20892 USA.
RI Su, Helen/H-9541-2015
OI Su, Helen/0000-0002-5582-9110
NR 0
TC 1
Z9 1
U1 0
U2 0
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 FEB
PY 2015
VL 135
IS 2
SU S
MA 832
BP AB256
EP AB256
PG 1
WC Allergy; Immunology
SC Allergy; Immunology
GA CR2BN
UT WOS:000361129600831
ER
PT J
AU Hillyer, P
Shepard, RE
Uehling, M
Sheik, F
Luongo, C
Buchholz, UJ
Collins, PL
Donnelly, RP
Rabin, RL
AF Hillyer, Philippa
Shepard, Rachel E.
Uehling, Megan
Sheik, Faruk
Luongo, Cindy
Buchholz, Ursula J.
Collins, Peter L.
Donnelly, Raymond P.
Rabin, Ronald L.
TI Respiratory Syncytial Virus-Induced Host IFN Signaling Differs Between
A549 and BEAS-2B Epithelial Cell Lines
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology
(AAAAI)
CY FEB 20-24, 2015
CL Houston, TX
SP Amer Acad Allergy, Asthma & Immunol
C1 [Hillyer, Philippa; Shepard, Rachel E.; Uehling, Megan; Rabin, Ronald L.] US FDA, CBER, Silver Spring, MD USA.
[Sheik, Faruk; Donnelly, Raymond P.] US FDA, CDER, Silver Spring, MD USA.
[Luongo, Cindy; Buchholz, Ursula J.; Collins, Peter L.] NIAID, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
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 FEB
PY 2015
VL 135
IS 2
SU S
MA 29
BP AB9
EP AB9
PG 1
WC Allergy; Immunology
SC Allergy; Immunology
GA CR2BN
UT WOS:000361129600030
ER
PT J
AU Khoury, P
Lee, CCR
Abiodun, AO
Klion, AD
AF Khoury, Paneez
Lee, Chyi-chia R.
Abiodun, Annalise O.
Klion, Amy D.
TI Skin Histopathology in Patients with Dermatologic Manifestations of
Hypereosinophilic Syndrome
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology
(AAAAI)
CY FEB 20-24, 2015
CL Houston, TX
SP Amer Acad Allergy, Asthma & Immunol
C1 [Khoury, Paneez; Lee, Chyi-chia R.; Abiodun, Annalise O.; Klion, Amy D.] NIH, Bethesda, MD 20892 USA.
[Abiodun, Annalise O.] Univ Utah, Sch Med, Salt Lake City, UT USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 FEB
PY 2015
VL 135
IS 2
SU S
MA 864
BP AB266
EP AB266
PG 1
WC Allergy; Immunology
SC Allergy; Immunology
GA CR2BN
UT WOS:000361129600863
ER
PT J
AU Kim, D
Beaven, MA
Cruse, G
Prussin, C
Komarow, H
Carter, MC
Metcalfe, DD
Olivera, A
AF Kim, Dokyun
Beaven, Michael A.
Cruse, Glenn
Prussin, Calman
Komarow, Hirsh
Carter, Melody C.
Metcalfe, Dean D.
Olivera, Ana
TI Constitutively Activated KIT in Mastocytosis Patients Is Associated with
Decreased Levels of the Scavenger Protein DJ1 and Reciprocal Increases
in Reactive Oxygen Species
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology
(AAAAI)
CY FEB 20-24, 2015
CL Houston, TX
SP Amer Acad Allergy, Asthma & Immunol
C1 [Kim, Dokyun; Cruse, Glenn; Prussin, Calman; Komarow, Hirsh; Carter, Melody C.; Metcalfe, Dean D.; Olivera, Ana] NIAID, Lab Allerg Dis, NIH, Bethesda, MD USA.
[Beaven, Michael A.] NHLBI, Lab Mol Immunol, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 2
U2 2
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 FEB
PY 2015
VL 135
IS 2
SU S
MA L27
BP AB389
EP AB389
PG 1
WC Allergy; Immunology
SC Allergy; Immunology
GA CR2BN
UT WOS:000361129600946
ER
PT J
AU Kirshenbaum, AS
Bandara, G
Desai, A
Fischer, E
Leerkes, M
Metcalfe, DD
Cruse, G
AF Kirshenbaum, Arnold S.
Bandara, Geethani
Desai, Avanti
Fischer, Elizabeth
Leerkes, Maarten
Metcalfe, Dean D.
Cruse, Glenn
TI Mast Cells Expressing the Germline HPS1 16-Bp Duplication
(c.1470_1486dup16, Hermansky-Pudlak Syndrome-1) Defect Produce
Extracellular Matrix Components
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology
(AAAAI)
CY FEB 20-24, 2015
CL Houston, TX
SP Amer Acad Allergy, Asthma & Immunol
C1 [Kirshenbaum, Arnold S.; Bandara, Geethani; Desai, Avanti; Fischer, Elizabeth; Metcalfe, Dean D.; Cruse, Glenn] NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA.
[Leerkes, Maarten] NIAID, Bioinformat & Computat Biosci Branch, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 FEB
PY 2015
VL 135
IS 2
SU S
MA 557
BP AB172
EP AB172
PG 1
WC Allergy; Immunology
SC Allergy; Immunology
GA CR2BN
UT WOS:000361129600556
ER
PT J
AU Knight, JM
Mak, G
Shaw, J
McDermott, C
Roberts, L
You, R
Yuan, XY
Millien, VO
Qian, YP
Song, LZ
Frazier, V
Kim, C
Kim, JJ
Bond, R
Luong, AU
Kheradmand, F
McMurray, J
Mandal, PK
Morlacchi, P
Milner, JD
Corry, DB
AF Knight, John M.
Mak, Garbo
Shaw, Joanne
McDermott, Catherine
Roberts, Luz
You, Ran
Yuan, Xiaoyi
Millien, Valentine O.
Qian, Yuping
Song, Li-Zhen
Frazier, Vincent
Kim, Choel
Kim, Jeong J.
Bond, Richard
Luong, Amber U.
Kheradmand, Farrah
McMurray, John
Mandal, Pijus K.
Morlacchi, Pietro
Milner, Joshua D.
Corry, David B.
TI Long-Acting Beta Agonists Enhance Allergic Airway Disease
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology
(AAAAI)
CY FEB 20-24, 2015
CL Houston, TX
SP Amer Acad Allergy, Asthma & Immunol
C1 [Knight, John M.; Mandal, Pijus K.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Knight, John M.; Mak, Garbo; McDermott, Catherine; Roberts, Luz; You, Ran; Yuan, Xiaoyi; Millien, Valentine O.; Song, Li-Zhen; Frazier, Vincent; Kim, Choel; Kim, Jeong J.] Baylor Coll Med, Houston, TX 77030 USA.
[Shaw, Joanne; Luong, Amber U.] Univ Texas Hlth Sci Ctr Houston, Houston, TX 77030 USA.
[Qian, Yuping; Kheradmand, Farrah; Corry, David B.] Baylor Coll Med, Houston, TX 77030 USA.
[Bond, Richard] Univ Houston, Houston, TX USA.
[McMurray, John; Morlacchi, Pietro] MD Anderson, Bethesda, MD USA.
[Milner, Joshua D.] NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 FEB
PY 2015
VL 135
IS 2
SU S
MA L2
BP AB381
EP AB381
PG 1
WC Allergy; Immunology
SC Allergy; Immunology
GA CR2BN
UT WOS:000361129600921
ER
PT J
AU Laffey, KG
Garnier, B
Hitchinson, B
Tarasova, N
Gaponenko, V
Ackerman, SJ
AF Laffey, Kimberly G.
Garnier, Boris
Hitchinson, Ben
Tarasova, Nadya
Gaponenko, Vadim
Ackerman, Steven J.
TI Development of a Novel Peptide Nanoparticle Inhibitor for Human
CCR3/Eotaxin-Mediated Eosinophil Migration
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology
(AAAAI)
CY FEB 20-24, 2015
CL Houston, TX
SP Amer Acad Allergy, Asthma & Immunol
C1 [Laffey, Kimberly G.; Garnier, Boris; Hitchinson, Ben; Gaponenko, Vadim; Ackerman, Steven J.] Univ Illinois, Chicago, IL USA.
[Tarasova, Nadya] NCI, Frederick, MD 21701 USA.
NR 0
TC 0
Z9 0
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 FEB
PY 2015
VL 135
IS 2
SU S
MA 523
BP AB160
EP AB160
PG 1
WC Allergy; Immunology
SC Allergy; Immunology
GA CR2BN
UT WOS:000361129600522
ER
PT J
AU Legrand, F
Alpaugh, A
Falahati, R
Makiya, M
Klion, AD
AF Legrand, Fanny
Alpaugh, Alexandra
Falahati, Rustom
Makiya, Michelle
Klion, Amy D.
TI A Novel Therapeutic Target for the Treatment of Eosinophilic Disorders
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology
(AAAAI)
CY FEB 20-24, 2015
CL Houston, TX
SP Amer Acad Allergy, Asthma & Immunol
C1 [Legrand, Fanny; Alpaugh, Alexandra; Makiya, Michelle; Klion, Amy D.] NIH, Bethesda, MD 20892 USA.
[Falahati, Rustom] Allakos Inc, San Carlos, CA USA.
RI Falahati, Rustom/Q-4098-2016
NR 0
TC 0
Z9 0
U1 0
U2 0
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 FEB
PY 2015
VL 135
IS 2
SU S
MA 716
BP AB221
EP AB221
PG 1
WC Allergy; Immunology
SC Allergy; Immunology
GA CR2BN
UT WOS:000361129600715
ER
PT J
AU Lyons, JJ
Yu, XM
Karpe, KA
Treadwell, SM
Ma, CA
O'Connell, MP
Sun, GP
Hughes, JD
Mehmet, H
McElwee, J
Holland, SM
Freeman, AF
Milner, JD
AF Lyons, Jonathan J.
Yu, Xiaomin
Karpe, Kendal A.
Treadwell, Shirin M.
Ma, Chi A.
O'Connell, Michael P.
Sun, Guangping
Hughes, Jason D.
Mehmet, Huseyin
McElwee, Joshua
Holland, Steven M.
Freeman, Alexandra F.
Milner, Joshua D.
TI Convergence of Clinical and Cellular Phenotypes Among Patients with
STAT3 and ERBB2IP Mutations
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology
(AAAAI)
CY FEB 20-24, 2015
CL Houston, TX
SP Amer Acad Allergy, Asthma & Immunol
C1 [Lyons, Jonathan J.; Yu, Xiaomin; Karpe, Kendal A.; Treadwell, Shirin M.; Ma, Chi A.; O'Connell, Michael P.; Sun, Guangping; Milner, Joshua D.] NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA.
[Hughes, Jason D.; Mehmet, Huseyin; McElwee, Joshua] Merck & Co Inc, Merck Res Labs, Boston, MA USA.
[Holland, Steven M.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
[Freeman, Alexandra F.] NIAID, NIH, Lab Clin Infect Dis, Bethesda, MD 20892 USA.
OI Lyons, Jonathan/0000-0002-2346-8189
NR 0
TC 0
Z9 0
U1 0
U2 2
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 FEB
PY 2015
VL 135
IS 2
SU S
MA 497
BP AB152
EP AB152
PG 1
WC Allergy; Immunology
SC Allergy; Immunology
GA CR2BN
UT WOS:000361129600496
ER
PT J
AU Moran, TP
Nakano, H
Nakano, K
Cook, D
AF Moran, Timothy P.
Nakano, Hideki
Nakano, Keiko
Cook, Donald
TI Inhalational Exposure to House Dust Conditions Pulmonary Conventional
Dendritic Cells to Induce T Helper 2 Responses Against Innocuous
Antigens
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology
(AAAAI)
CY FEB 20-24, 2015
CL Houston, TX
SP Amer Acad Allergy, Asthma & Immunol
C1 [Moran, Timothy P.] Univ N Carolina, Chapel Hill, NC USA.
[Nakano, Hideki; Nakano, Keiko; Cook, Donald] NIEHS, NIH, Res Triangle Pk, NC 27709 USA.
NR 0
TC 0
Z9 0
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 FEB
PY 2015
VL 135
IS 2
SU S
MA 898
BP AB276
EP AB276
PG 1
WC Allergy; Immunology
SC Allergy; Immunology
GA CR2BN
UT WOS:000361129600897
ER
PT J
AU Mueller, G
Pedersen, L
Glesner, J
Edwards, LL
Zakzuk, J
London, R
Arruda, LKP
Chapman, MD
Caraballo, L
Pomes, A
AF Mueller, Geoffrey
Pedersen, Lars
Glesner, Jill
Edwards, Lori L.
Zakzuk, Josefina
London, Robert
Arruda, Luisa Karla P.
Chapman, Martin D.
Caraballo, Luis
Pomes, Anna
TI Analysis of GST Allergen Cross-Reactivity in a North American Population
for Molecular Diagnosis
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology
(AAAAI)
CY FEB 20-24, 2015
CL Houston, TX
SP Amer Acad Allergy, Asthma & Immunol
C1 [Mueller, Geoffrey; Pedersen, Lars; Edwards, Lori L.; London, Robert] NIEHS, NIH, Res Triangle Pk, NC 27709 USA.
[Glesner, Jill; Chapman, Martin D.; Pomes, Anna] Indoor Biotechnol Inc, Charlottesville, VA USA.
[Zakzuk, Josefina; Caraballo, Luis] Univ Cartagena, Inst Immunol Res, Cartagena, Colombia.
[Arruda, Luisa Karla P.] Univ Sao Paulo, Ribeirao Preto Med Sch, BR-14049 Ribeirao Preto, Brazil.
RI Arruda, L. Karla /D-5845-2013
OI Arruda, L. Karla /0000-0002-7505-210X
NR 0
TC 0
Z9 0
U1 0
U2 2
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 FEB
PY 2015
VL 135
IS 2
SU S
MA 604
BP AB187
EP AB187
PG 1
WC Allergy; Immunology
SC Allergy; Immunology
GA CR2BN
UT WOS:000361129600603
ER
PT J
AU Nayak, AP
Green, BJ
Croston, TL
Lemons, AR
Marshall, NB
Goldsmith, WT
Kashon, M
Law, BF
Wagner, LM
Long, CM
Germolec, DM
Beezhold, DH
AF Nayak, Ajay P.
Green, Brett J.
Croston, Tara L.
Lemons, Angela R.
Marshall, Nikki B.
Goldsmith, W. Travis
Kashon, Michael
Law, Brandon F.
Wagner, Lauren M.
Long, Carrie M.
Germolec, Dori M.
Beezhold, Donald H.
TI Characterization of Antigen Presenting Cells in a Murine Subchronic
Fungal Exposure Model
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology
(AAAAI)
CY FEB 20-24, 2015
CL Houston, TX
SP Amer Acad Allergy, Asthma & Immunol
C1 [Nayak, Ajay P.; Green, Brett J.; Croston, Tara L.; Lemons, Angela R.; Marshall, Nikki B.; Law, Brandon F.; Wagner, Lauren M.; Long, Carrie M.; Beezhold, Donald H.] NIOSH, CDC, ACIB, Morgantown, WV USA.
[Goldsmith, W. Travis] NIOSH, CDC, PPRB, Morgantown, WV USA.
[Kashon, Michael] NIOSH, CDC, BEB, Morgantown, WV USA.
[Germolec, Dori M.] NIEHS, NTP, Res Triangle Pk, NC 27709 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
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 FEB
PY 2015
VL 135
IS 2
SU S
MA 59
BP AB19
EP AB19
PG 1
WC Allergy; Immunology
SC Allergy; Immunology
GA CR2BN
UT WOS:000361129600060
ER
PT J
AU O'Connell, MP
Hox, V
Nelson, C
DiMaggio, T
Jones, N
Sackstein, P
Freeman, AF
Olivera, A
Metcalfe, DD
Milner, JD
AF O'Connell, Michael P.
Hox, Valerie
Nelson, Celeste
DiMaggio, Thomas
Jones, Nina
Sackstein, Paul
Freeman, Alexandra F.
Olivera, Ana
Metcalfe, Dean D.
Milner, Joshua D.
TI Deficiencies in STAT3 Signaling Confers Resistance to Histamine/PAF
Induced Vascular Permeability in Autosomal Dominant-Hyper IgE Syndrome
(AD-HIES)
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology
(AAAAI)
CY FEB 20-24, 2015
CL Houston, TX
SP Amer Acad Allergy, Asthma & Immunol
C1 [O'Connell, Michael P.; Hox, Valerie; Nelson, Celeste; DiMaggio, Thomas; Sackstein, Paul; Olivera, Ana; Metcalfe, Dean D.; Milner, Joshua D.] NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA.
[Jones, Nina] Frederick Natl Lab Clin Res, Frederick, MD USA.
[Freeman, Alexandra F.] NIAID, NIH, Lab Clin Infect Dis, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
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 FEB
PY 2015
VL 135
IS 2
SU S
MA 648
BP AB200
EP AB200
PG 1
WC Allergy; Immunology
SC Allergy; Immunology
GA CR2BN
UT WOS:000361129600647
ER
PT J
AU Pomes, A
Glesner, J
Woodfolk, JA
Wright, P
Kepley, CL
Li, M
Himly, M
Gustchina, A
Wlodawer, A
Chapman, MD
AF Pomes, Anna
Glesner, Jill
Woodfolk, Judith A.
Wright, Paul
Kepley, Christopher L.
Li, Mi
Himly, Martin
Gustchina, Alla
Wlodawer, Alexander
Chapman, Martin D.
TI Bla g 2 Hypoallergens Retaining the Native Fold and Capacity to Modulate
T Cell Reactivity Provide Candidates for Cockroach Immunotherapy
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology
(AAAAI)
CY FEB 20-24, 2015
CL Houston, TX
SP Amer Acad Allergy, Asthma & Immunol
C1 [Pomes, Anna; Glesner, Jill; Chapman, Martin D.] Indoor Biotechnol Inc, Charlottesville, VA USA.
[Woodfolk, Judith A.] Univ Virginia Hlth Syst, Div Asthma Allergy & Immunol, Charlottesville, VA USA.
[Wright, Paul] Univ Virginia, Charlottesville, VA USA.
[Kepley, Christopher L.] Univ N Carolina, Joint Sch Nanosci & Nanoengn, Greensboro, NC 27412 USA.
[Li, Mi; Gustchina, Alla; Wlodawer, Alexander] NCI, Frederick, MD 21701 USA.
[Himly, Martin] Salzburg Univ, A-5020 Salzburg, Austria.
RI Himly, Martin/D-1568-2015
OI Himly, Martin/0000-0001-5416-085X
NR 0
TC 0
Z9 0
U1 0
U2 1
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 FEB
PY 2015
VL 135
IS 2
SU S
MA 536
BP AB165
EP AB165
PG 1
WC Allergy; Immunology
SC Allergy; Immunology
GA CR2BN
UT WOS:000361129600535
ER
PT J
AU Salo, PM
Jaramillo, R
Rose, KM
Calatroni, A
Mitchell, H
Zeldin, DC
AF Salo, Paivi M.
Jaramillo, Renee
Rose, Kathryn M.
Calatroni, Agustin
Mitchell, Herman
Zeldin, Darryl C.
TI Predictors of Bedroom Allergen Exposures in US Homes
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology
(AAAAI)
CY FEB 20-24, 2015
CL Houston, TX
SP Amer Acad Allergy, Asthma & Immunol
C1 [Salo, Paivi M.; Zeldin, Darryl C.] NIEHS, Environm Cardiopulm Dis Grp, Immun Inflammat & Dis Lab, Div Intramural Res,NIH, Res Triangle Pk, NC 27709 USA.
[Jaramillo, Renee; Rose, Kathryn M.] Social & Sci Syst Inc, Durham, NC USA.
[Calatroni, Agustin; Mitchell, Herman] Rho Inc, Chapel Hill, NC USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
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 FEB
PY 2015
VL 135
IS 2
SU S
MA 66
BP AB21
EP AB21
PG 1
WC Allergy; Immunology
SC Allergy; Immunology
GA CR2BN
UT WOS:000361129600067
ER
PT J
AU Spergel, AKR
Chen, CC
Beegle, CA
Littel, P
Garofalo, M
Anaya-O'Brien, S
Marquesen, M
Bagci, U
Mollura, DJ
Gallin, JI
Malech, HL
AF Spergel, Amanda K. Rudman
Chen, Clara C.
Beegle, Cheryl Ann
Littel, Patricia
Garofalo, Mary
Anaya-O'Brien, Sandra
Marquesen, Martha
Bagci, Ulas
Mollura, Daniel J.
Gallin, John I.
Malech, Harry L.
TI The Use of Radiolabelled 18-F-2-Deoxy-2-Fluro-Glucose (18-FDG) in
Combined Positron Emission Tomography-Computed Tomography (PET-CT) to
Evaluate Infection: Lessons Learned from a Case Series of 23 Patients
with Chronic Granulomatous Disease (CGD)
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology
(AAAAI)
CY FEB 20-24, 2015
CL Houston, TX
SP Amer Acad Allergy, Asthma & Immunol
C1 [Spergel, Amanda K. Rudman; Littel, Patricia; Garofalo, Mary; Anaya-O'Brien, Sandra; Marquesen, Martha; Gallin, John I.; Malech, Harry L.] NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA.
[Chen, Clara C.; Beegle, Cheryl Ann] NIH, Nucl Med Sect, Radiol & Imaging Sci, Ctr Clin, Bethesda, MD 20892 USA.
[Bagci, Ulas; Mollura, Daniel J.] NIH, Ctr Infect Dis Imaging Radiol & Imaging Sci, Ctr Clin, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
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 FEB
PY 2015
VL 135
IS 2
SU S
MA 316
BP AB98
EP AB98
PG 1
WC Allergy; Immunology
SC Allergy; Immunology
GA CR2BN
UT WOS:000361129600316
ER
PT J
AU Wessell, KMR
Holland, S
Lisco, A
Roifman, CM
Tcheurekdjian, H
Hostoffer, RW
AF Wessell, Kathryn Marie Ruda
Holland, Steven
Lisco, Andrea
Roifman, Chaim M.
Tcheurekdjian, Haig
Hostoffer, Robert W.
TI A Young Adult Male with Chronic Mucocutaneous Candidiasis (CMC) with
Signal Transduction and Activator of Transcription 1 (STAT 1) Mutation
and Progressive Multifocal Leukoencephalopathy (PML)
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology
(AAAAI)
CY FEB 20-24, 2015
CL Houston, TX
SP Amer Acad Allergy, Asthma & Immunol
C1 [Wessell, Kathryn Marie Ruda] Univ Hosp Reg Hosp Cleveland, South Euclid, OH USA.
[Holland, Steven] NIH, Bethesda, MD 20892 USA.
[Lisco, Andrea] Univ Hosp Case Med Ctr Cleveland Ohio, Cleveland, OH USA.
[Roifman, Chaim M.] Hosp Sick Children, Toronto, ON M5G 1X8, Canada.
[Tcheurekdjian, Haig; Hostoffer, Robert W.] Allergy Immunol Associates Inc, South Euclid, OH USA.
NR 0
TC 2
Z9 2
U1 0
U2 0
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 FEB
PY 2015
VL 135
IS 2
SU S
MA 601
BP AB186
EP AB186
PG 1
WC Allergy; Immunology
SC Allergy; Immunology
GA CR2BN
UT WOS:000361129600600
ER
PT J
AU Williams, KW
McGowan, K
Sowerwine, KJ
Davis, J
Holland, SM
Freeman, AF
AF Williams, Kelli W.
McGowan, Katherine
Sowerwine, Kathryn J.
Davis, Joie
Holland, Steven M.
Freeman, Alexandra F.
TI Prompt Diagnosis of Autosomal Dominant Hyper IgE Syndrome Leads to
Reduced Infection and Improved Clinical Phenotype
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology
(AAAAI)
CY FEB 20-24, 2015
CL Houston, TX
SP Amer Acad Allergy, Asthma & Immunol
C1 [Williams, Kelli W.; McGowan, Katherine; Davis, Joie; Holland, Steven M.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
[Sowerwine, Kathryn J.] Dermatol Specialists Virgnia, Reston, VA USA.
[Freeman, Alexandra F.] NIAID, NIH, Lab Clin Infect Dis, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 FEB
PY 2015
VL 135
IS 2
SU S
MA 590
BP AB183
EP AB183
PG 1
WC Allergy; Immunology
SC Allergy; Immunology
GA CR2BN
UT WOS:000361129600589
ER
PT J
AU Yang, I
Liu, AH
Pedersen, B
O'Connor, GT
Teach, SJ
Kattan, M
Misiak, RT
Gruchalla, RS
Steinbach, SF
Szefler, SJ
Gill, MA
Calatroni, A
David, GL
Hennessy, CE
Davidson, EJ
Zhang, WM
Gergen, PJ
Togias, A
Busse, WW
Schwartz, DA
AF Yang, Ivana
Liu, Andrew H.
Pedersen, Brent
O'Connor, George T.
Teach, Stephen J.
Kattan, Meyer
Misiak, Rana T.
Gruchalla, Rebecca S.
Steinbach, Suzanne F.
Szefler, Stanley J.
Gill, Michelle A.
Calatroni, Agustin
David, Gloria L.
Hennessy, Corinne E.
Davidson, Elizabeth J.
Zhang, Weiming
Gergen, Peter J.
Togias, Alkis
Busse, William W.
Schwartz, David A.
TI DNA Methylation and Childhood Asthma in the Inner-City
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology
(AAAAI)
CY FEB 20-24, 2015
CL Houston, TX
SP Amer Acad Allergy, Asthma & Immunol
C1 [Yang, Ivana] Univ Colorado Denver, Dept Med, Denver, CO USA.
[Liu, Andrew H.] Univ Colorado, Sch Med, Aurora, CO USA.
[Liu, Andrew H.] Natl Jewish Hlth, Denver, CO USA.
[Pedersen, Brent] Univ Colorado, Aurora, CO USA.
[O'Connor, George T.; Steinbach, Suzanne F.] Boston Univ, Sch Med, Boston, MA 02118 USA.
[Teach, Stephen J.] Childrens Natl Hlth Syst, Washington, DC USA.
[Kattan, Meyer] NewYork Presbyterian Columbia, New York, NY USA.
[Misiak, Rana T.] Henry Ford Hlth Syst, Northville, MI USA.
[Gruchalla, Rebecca S.; Gill, Michelle A.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA.
[Szefler, Stanley J.] Childrens Hosp Colorado, Breathing Inst, Aurora, CO USA.
[Calatroni, Agustin; David, Gloria L.] Rho Inc, Chapel Hill, NC USA.
[Hennessy, Corinne E.; Davidson, Elizabeth J.] Univ Colorado, Sch Med, Boulder, CO 80309 USA.
[Zhang, Weiming] Univ Colorado, Colorado Sch Publ Hlth, Boulder, CO 80309 USA.
[Gergen, Peter J.] NIH, AAIB, DAIT, Bethesda, MD 20892 USA.
[Togias, Alkis] NIAID, NIH, Bethesda, MD 20892 USA.
[Busse, William W.] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI USA.
[Schwartz, David A.] Univ Colorado Denver, Sch Med, Aurora, CO USA.
NR 0
TC 0
Z9 0
U1 1
U2 2
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 FEB
PY 2015
VL 135
IS 2
SU S
MA 530
BP AB163
EP AB163
PG 1
WC Allergy; Immunology
SC Allergy; Immunology
GA CR2BN
UT WOS:000361129600529
ER
PT J
AU Yang, Q
Ge, MQ
Kubala, S
Jiang, ZL
Redai, IG
Soni, M
Chen, B
Cohen, NA
Bhandoola, A
Haczku, A
AF Yang, Qi
Ge, Moyar Q.
Kubala, Stephanie
Jiang, Zhilong
Redai, Imre G.
Soni, Monica
Chen, Bei
Cohen, Noam A.
Bhandoola, Avinash
Haczku, Angela
TI Epithelial IL-33 and TSLP Elicit Innate Lymphoid Cell Responses to
Mediate Ozone-Induced Airway Inflammation and Hyperresponsiveness
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology
(AAAAI)
CY FEB 20-24, 2015
CL Houston, TX
SP Amer Acad Allergy, Asthma & Immunol
C1 [Yang, Qi; Ge, Moyar Q.; Kubala, Stephanie; Jiang, Zhilong; Redai, Imre G.; Soni, Monica; Chen, Bei] Univ Penn, Philadelphia, PA 19104 USA.
[Cohen, Noam A.] Dept Otorhinolaryngol Head & Neck, Philadelphia, PA USA.
[Bhandoola, Avinash] NCI, NIH, Bethesda, MD 20892 USA.
[Haczku, Angela] Univ Calif Davis, Davis, CA 95616 USA.
RI Ge, Qing/N-5855-2016
NR 0
TC 0
Z9 0
U1 0
U2 2
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 FEB
PY 2015
VL 135
IS 2
SU S
MA 263
BP AB82
EP AB82
PG 1
WC Allergy; Immunology
SC Allergy; Immunology
GA CR2BN
UT WOS:000361129600263
ER
PT J
AU Yin, YZ
Prussin, C
AF Yin, Yuzhi
Prussin, Calman
TI Rapamycin Preferentially Inhibits IL5+Th2 Cell Proliferation through the
mTORC1/S6 Kinase Pathway
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology
(AAAAI)
CY FEB 20-24, 2015
CL Houston, TX
SP Amer Acad Allergy, Asthma & Immunol
C1 [Yin, Yuzhi; Prussin, Calman] NIAID, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
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 FEB
PY 2015
VL 135
IS 2
SU S
MA 266
BP AB83
EP AB83
PG 1
WC Allergy; Immunology
SC Allergy; Immunology
GA CR2BN
UT WOS:000361129600266
ER
PT J
AU Cerbini, T
Luo, YQ
Rao, MS
Zou, JZ
AF Cerbini, Trevor
Luo, Yongquan
Rao, Mahendra S.
Zou, Jizhong
TI Transfection, Selection, and Colony-picking of Human Induced Pluripotent
Stem Cells TALEN-targeted with a GFP Gene into the AAVS1 Safe Harbor
SO JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
LA English
DT Article
DE Developmental Biology; Issue 96; induced pluripotent stem cell; gene
editing; AAVS1; TALEN; GFP
ID INTEGRATION; NUCLEASES; EXPRESSION; DISEASE
AB Targeted transgene addition can provide persistent gene expression while circumventing the gene silencing and insertional mutagenesis caused by viral vector mediated random integration. This protocol describes a universal and efficient transgene targeted addition platform in human iPSCs based on utilization of validated open-source TALENs and a gene-trap-like donor to deliver transgenes into a safe harbor locus. Importantly, effective gene editing is rate-limited by the delivery efficiency of gene editing vectors. Therefore, this protocol first focuses on preparation of iPSCs for transfection to achieve high nuclear delivery efficiency. When iPSCs are dissociated into single cells using a gentle-cell dissociation reagent and transfected using an optimized program,>50% cells can be induced to take up the large gene editing vectors. Because the AAVS1 locus is located in the intron of an active gene (PPP1R12C), a splicing acceptor (SA)-linked puromycin resistant gene (PAC) was used to select targeted iPSCs while excluding random integration-only and untransfected cells. This strategy greatly increases the chance of obtaining targeted clones, and can be used in other active gene targeting experiments as well. Two weeks after puromycin selection at the dose adjusted for the specific iPSC line, clones are ready to be picked by manual dissection of large, isolated colonies into smaller pieces that are transferred to fresh medium in a smaller well for further expansion and genetic and functional screening. One can follow this protocol to readily obtain multiple GFP reporter iPSC lines that are useful for in vivo and in vitro imaging and cell isolation.
C1 [Cerbini, Trevor; Luo, Yongquan; Zou, Jizhong] NIAMSD, NIH, Bethesda, MD 20892 USA.
RP Zou, JZ (reprint author), NIAMSD, NIH, Bethesda, MD 20892 USA.
EM jizhong.zou@nih.gov
FU NIH; Intramural Research Program of the National Institute of Arthritis,
Musculoskeletal, and Skin Diseases
FX This research was supported by the NIH Common Fund and Intramural
Research Program of the National Institute of Arthritis,
Musculoskeletal, and Skin Diseases.
NR 19
TC 1
Z9 1
U1 1
U2 8
PU JOURNAL OF VISUALIZED EXPERIMENTS
PI CAMBRIDGE
PA 1 ALEWIFE CENTER, STE 200, CAMBRIDGE, MA 02140 USA
SN 1940-087X
J9 JOVE-J VIS EXP
JI J. Vis. Exp.
PD FEB
PY 2015
IS 96
AR e52504
DI 10.3791/52504
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CR7MH
UT WOS:000361533700065
ER
PT J
AU House, CD
Hernandez, L
Annunziata, CM
AF House, Carrie D.
Hernandez, Lidia
Annunziata, Christina M.
TI In vitro Enrichment of Ovarian Cancer Tumor-initiating Cells
SO JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
LA English
DT Article
DE Medicine; Issue 96; Ovarian cancer; tumor-initiating cells; cancer stem
cell; tumorigenicity; spheroid; mouse; gynecological cancer
ID STEM-CELLS; FALLOPIAN-TUBE; EPITHELIAL-CELLS; CD133; DEFINES; NANOG;
POPULATION; RESISTANCE; CARCINOMA; IMPACT
AB Evidence suggests that small subpopulations of tumor cells maintain a unique self-renewing and differentiation capacity and may be responsible for tumor initiation and/or relapse. Clarifying the mechanisms by which these tumor-initiating cells (TICs) support tumor formation and progression could lead to the development of clinically favorable therapies. Ovarian cancer is a heterogeneous and highly recurrent disease. Recent studies suggest TICs may play an important role in disease biology. We have identified culture conditions that enrich for TICs from ovarian cancer cell lines. Growing either adherent cells or non-adherent 'floater' cells in a low attachment plate with serum free media in the presence of growth factors supports the propagation of ovarian cancer TICs with stem cell markers (CD133 and ALDH activity) and increased tumorigenicity without the need to physically separate the TICs from other cell types within the culture. Although the presence of floater cells is not common for all cell lines, this population of cells with innate low adherence may have high tumorigenic potential. Compared to adherent cells grown in the presence of serum, TICs readily form spheres, are significantly more tumorigenic in mice, and express putative stem cell markers. The conditions are easy to establish in a timely manner and can be used to study signaling pathways important for maintaining stem characteristics, and to identify drugs or combinations of drugs targeting TICs. The culture conditions described herein are applicable for a variety of ovarian cancer cells of epithelial origin and will be critical in providing new information about the role of TICs in tumor initiation, progression, and relapse.
C1 [House, Carrie D.; Hernandez, Lidia; Annunziata, Christina M.] NCI, Womens Malignancies Branch, Bethesda, MD 20892 USA.
RP Annunziata, CM (reprint author), NCI, Womens Malignancies Branch, Bethesda, MD 20892 USA.
EM annunzic@mail.nih.gov
RI Annunziata, Christina/L-3219-2016
OI Annunziata, Christina/0000-0003-2033-6532
FU National Institute for General Medical Sciences
FX We thank Dr. John Risinger and Memorial Health University Medical
Center, Inc. for generously providing the ACI-23 cell line. The authors
acknowledge financial support through the Postdoctoral Research Training
(PRAT) Award to C. House from The National Institute for General Medical
Sciences.
NR 35
TC 1
Z9 2
U1 2
U2 2
PU JOURNAL OF VISUALIZED EXPERIMENTS
PI CAMBRIDGE
PA 1 ALEWIFE CENTER, STE 200, CAMBRIDGE, MA 02140 USA
SN 1940-087X
J9 JOVE-J VIS EXP
JI J. Vis. Exp.
PD FEB
PY 2015
IS 96
AR e52446
DI 10.3791/52446
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CR7MH
UT WOS:000361533700052
ER
PT J
AU Aufforth, R
Boufraqech, M
Li-Chittenden, Y
Zhang, Y
Shen, M
Gaskins, K
Zhang, L
Kebebew, E
AF Aufforth, R.
Boufraqech, M.
Li-Chittenden, Y.
Zhang, Y.
Shen, M.
Gaskins, K.
Zhang, L.
Kebebew, E.
TI Quantitative High Throughput Screening Identifies Carfilzomib as an
Effective Anticancer Agent for Adrenocortical Carcinoma
SO ANNALS OF SURGICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 68th Annual Cancer Symposium of the Society-of-Surgical-Oncology
CY MAR 25-28, 2015
CL Houston, TX
SP Soc Surg Oncol
C1 [Aufforth, R.; Boufraqech, M.; Li-Chittenden, Y.; Gaskins, K.; Zhang, L.; Kebebew, E.] NCI, Endocrine Oncol, Washington, DC USA.
[Zhang, Y.; Shen, M.] Natl Ctr Adv Translat Sci, Bethesda, MD USA.
RI Boufraqech, Myriem/E-4823-2016
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1068-9265
EI 1534-4681
J9 ANN SURG ONCOL
JI Ann. Surg. Oncol.
PD FEB
PY 2015
VL 22
SU 1
MA 68
BP S29
EP S29
PG 1
WC Oncology; Surgery
SC Oncology; Surgery
GA CQ9MZ
UT WOS:000360940500068
ER
PT J
AU Beane, JD
Chen, I
Steinberg, S
Rudloff, U
AF Beane, J. D.
Chen, I.
Steinberg, S.
Rudloff, U.
TI Novel Genotype-phenotype Correlations in Patients with Hereditary
Diffuse Gastric Cancer
SO ANNALS OF SURGICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 68th Annual Cancer Symposium of the Society-of-Surgical-Oncology
CY MAR 25-28, 2015
CL Houston, TX
SP Soc Surg Oncol
C1 [Chen, I.; Rudloff, U.] NIH, Ctr Canc Res, GI & Thorac Oncol Branch, Bethesda, MD 20892 USA.
[Steinberg, S.] NCI, Ctr Canc Res, Biostat & Data Management Sect, Bethesda, MD 20892 USA.
[Beane, J. D.] Indiana Univ Sch Med, Dept Surg, Indianapolis, IN 46202 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1068-9265
EI 1534-4681
J9 ANN SURG ONCOL
JI Ann. Surg. Oncol.
PD FEB
PY 2015
VL 22
SU 1
MA P403
BP S177
EP S177
PG 1
WC Oncology; Surgery
SC Oncology; Surgery
GA CQ9MZ
UT WOS:000360940500494
ER
PT J
AU Hiroshima, Y
Maawy, A
Zhang, Y
Murakami, T
De Magalhaes, N
Garcia-Guzman, M
Heim, R
Makings, L
Luiken, G
Kobayashi, H
Hoffman, R
Bouvet, M
AF Hiroshima, Y.
Maawy, A.
Zhang, Y.
Murakami, T.
De Magalhaes, N.
Garcia-Guzman, M.
Heim, R.
Makings, L.
Luiken, G.
Kobayashi, H.
Hoffman, R.
Bouvet, M.
TI Efficacy of Photoimmunotherapy after Surgical Resection on a Pancreatic
Cancer Patient Derived Orthotopic Xenograft (PDOX) Nude Mouse Model
SO ANNALS OF SURGICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 68th Annual Cancer Symposium of the Society-of-Surgical-Oncology
CY MAR 25-28, 2015
CL Houston, TX
SP Soc Surg Oncol
C1 [Maawy, A.; De Magalhaes, N.; Bouvet, M.] Univ Calif San Diego, Surg, La Jolla, CA 92093 USA.
[Hiroshima, Y.; Zhang, Y.; Murakami, T.; Hoffman, R.] AntiCancer Inc, San Diego, CA USA.
[Garcia-Guzman, M.; Heim, R.; Makings, L.] Aspyrian Therapeut Inc, San Diego, CA USA.
[Luiken, G.] OncoFluor, San Diego, CA USA.
[Kobayashi, H.] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1068-9265
EI 1534-4681
J9 ANN SURG ONCOL
JI Ann. Surg. Oncol.
PD FEB
PY 2015
VL 22
SU 1
MA P393
BP S173
EP S174
PG 2
WC Oncology; Surgery
SC Oncology; Surgery
GA CQ9MZ
UT WOS:000360940500485
ER
PT J
AU Schaub, N
Bapiro, T
Pflicke, H
Chen, I
Avital, I
Schrump, D
Jodrell, D
Rudloff, U
AF Schaub, N.
Bapiro, T.
Pflicke, H.
Chen, I.
Avital, I.
Schrump, D.
Jodrell, D.
Rudloff, U.
TI Gemcitabine Cooperates with TGF beta Inhibition to Effectively Suppress
Tumor Growth in Genetically Engineered Mouse Models of Pancreas Cancer
SO ANNALS OF SURGICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 68th Annual Cancer Symposium of the Society-of-Surgical-Oncology
CY MAR 25-28, 2015
CL Houston, TX
SP Soc Surg Oncol
C1 [Schaub, N.; Pflicke, H.; Chen, I.; Schrump, D.; Rudloff, U.] NCI, Thorac & GI Oncol Branch, Surg Branch, NIH, Bethesda, MD 20892 USA.
[Bapiro, T.; Jodrell, D.] Cambridge Res Inst, Canc Res UK, Cambridge, England.
[Avital, I.] Bon Secours Canc Inst, Richmond, VA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1068-9265
EI 1534-4681
J9 ANN SURG ONCOL
JI Ann. Surg. Oncol.
PD FEB
PY 2015
VL 22
SU 1
MA P411
BP S178
EP S179
PG 2
WC Oncology; Surgery
SC Oncology; Surgery
GA CQ9MZ
UT WOS:000360940500501
ER
PT J
AU Schaub, N
Sorber, R
Janes, J
Lopez, H
Martin, G
Rudloff, U
AF Schaub, N.
Sorber, R.
Janes, J.
Lopez, H.
Martin, G.
Rudloff, U.
TI An Immunomodulating Peptide that Enhances Gemcitabine Inhibition of
Pancreatic Growth in the KRAS/p16 Mouse Model of Pancreatic Cancer
SO ANNALS OF SURGICAL ONCOLOGY
LA English
DT Meeting Abstract
CT 68th Annual Cancer Symposium of the Society-of-Surgical-Oncology (SSO)
CY MAR 25-28, 2015
CL Houston, TX
SP Soc Surg Oncol
C1 [Schaub, N.; Rudloff, U.] NCI, Thorac & GI Oncol Branch, Surg Branch, NIH, Bethesda, MD 20892 USA.
[Sorber, R.] Indiana Univ, Dept Surg, Indianapolis, IN 46204 USA.
[Janes, J.] Tuskegee Univ, Tuskegee, AL 36088 USA.
[Lopez, H.] Murigenics Inc, Vallejo, CA USA.
[Martin, G.] Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1068-9265
EI 1534-4681
J9 ANN SURG ONCOL
JI Ann. Surg. Oncol.
PD FEB
PY 2015
VL 22
SU 1
MA P407
BP S178
EP S178
PG 1
WC Oncology; Surgery
SC Oncology; Surgery
GA CQ9MZ
UT WOS:000360940500498
ER
PT J
AU Janes, K
Wahlman, C
Little, JW
Doyle, T
Tosh, DK
Jacobson, KA
Salvemini, D
AF Janes, Kali
Wahlman, Carrie
Little, Joshua W.
Doyle, Timothy
Tosh, Dillip K.
Jacobson, Kenneth A.
Salvemini, Daniela
TI Spinal neuroimmune activation is independent of T-cell infiltration and
attenuated by A(3) adenosine receptor agonists in a model of
oxaliplatin-induced peripheral neuropathy
SO BRAIN BEHAVIOR AND IMMUNITY
LA English
DT Article
DE Adenosine; A3 adenosine receptor; Neuroinflammation;
Chemotherapy-induced peripheral neuropathy; Neuropathic pain;
Oxaliplatin; Astrocytes; Spinal cord
ID DORSAL-ROOT GANGLIA; NF-KAPPA-B; RHEUMATOID-ARTHRITIS;
HEPATOCELLULAR-CARCINOMA; INTERNATIONAL UNION; CANCER-THERAPY;
UP-REGULATION; CHRONIC PAIN; TNF-ALPHA; PACLITAXEL
AB Many commonly used chemotherapeutics including oxaliplatin are associated with the development of a painful chemotherapy-induced peripheral neuropathy (CIPN). This dose-limiting complication can appear long after the completion of therapy causing a significant reduction in quality-of-life and impeding cancer treatment. We recently reported that activation of the G(i)/G(q)-coupled A(3) adenosine receptor (A(3)Ag) with selective A(3)AR agonists (i.e.. IB-MECA) blocked the development of chemotherapy induced-neuropathic pain in models evoked by distinct agents including oxaliplatin without interfering with their anticancer activities. The mechanism(s) of action underlying these beneficial effects has yet to be explored. Our results herein demonstrate that the development of oxaliplatin-induced mechano-hypersensitivity (allodynia and hyperalgesia) in rats is associated with the hyperactivation of astrocytes, but not microglial cells, increased production of pro-inflammatory and neuroexcitatory cytokines (TNF, IL-1 beta), and reductions in the levels of anti-inflammatory/neuroprotective cytokines (IL-10, IL-4) in the dorsal horn of the spinal cord. These events did not require lymphocytic mobilization since oxaliplatin did not induce CD45(+)/CD3(+) T-cell infiltration into the spinal cord. A(3)AR agonists blocked the development of neuropathic pain with beneficial effects strongly associated with the modulation of spinal neuroinflammatory processes: attenuation of astrocytic hyperactivation, inhibition of TNF and IL-1 beta production, and an increase in IL-10 and IL-4. These results suggest that inhibition of an astrocyte-associated neuroinflammatory response contributes to the protective actions of A(3)AR signaling and continues to support the pharmacological basis for selective A(3)AR agonists as adjuncts to chemotherapeutic agents for the management of chronic pain. (C) 2014 Elsevier Inc. All rights reserved.
C1 [Janes, Kali; Wahlman, Carrie; Little, Joshua W.; Doyle, Timothy; Salvemini, Daniela] St Louis Univ, Sch Med, Dept Pharmacol & Physiol Sci, St Louis, MO 63104 USA.
[Tosh, Dillip K.; Jacobson, Kenneth A.] NIDDK, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
RP Salvemini, D (reprint author), St Louis Univ, Sch Med, Dept Pharmacol & Physiol Sci, 1402 South Grand Blvd, St Louis, MO 63104 USA.
EM salvemd@slu.edu
RI Jacobson, Kenneth/A-1530-2009
OI Jacobson, Kenneth/0000-0001-8104-1493
FU National Cancer Institute [RO1CA169519]; Saint Louis Cancer Center;
NIDDK Intramural Research Program
FX We would like to thank Leesa Bryant for her technical assistance in
performing some of the animal experiments. This study was funded by
grants from the National Cancer Institute (RO1CA169519) with additional
support from the Saint Louis Cancer Center, and the NIDDK Intramural
Research Program.
NR 72
TC 17
Z9 18
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 0889-1591
EI 1090-2139
J9 BRAIN BEHAV IMMUN
JI Brain Behav. Immun.
PD FEB
PY 2015
VL 44
BP 91
EP 99
DI 10.1016/j.bbi.2014.08.010
PG 9
WC Immunology; Neurosciences
SC Immunology; Neurosciences & Neurology
GA CQ4RS
UT WOS:000360592900012
PM 25220279
ER
PT J
AU Lewis, SS
Hutchinson, MR
Frick, MM
Zhang, YN
Maier, SF
Sammakia, T
Rice, KC
Watkins, LR
AF Lewis, Susannah S.
Hutchinson, Mark R.
Frick, Morin M.
Zhang, Yingning
Maier, Steven F.
Sammakia, Tarek
Rice, Kenner C.
Watkins, Linda R.
TI Select steroid hormone glucuronide metabolites can cause toll-like
receptor 4 activation and enhanced pain
SO BRAIN BEHAVIOR AND IMMUNITY
LA English
DT Article
DE Corticosterone; Corticosterone-21-glucuronide; Estradiol;
Estradiol-17-glucuronide; Estradiol-3-glucuronide; TLR4; (+)-Naloxone
ID MENSTRUAL-CYCLE; LIPOPOLYSACCHARIDE; STRESS; HYPERALGESIA; RECOGNITION;
PREVALENCE; MECHANISMS; ALLODYNIA; ESTROGENS; MIGRAINE
AB We have recently shown that several classes of glucuronide metabolites, including the morphine metabolite morphine-3-glucuronide and the ethanol metabolite ethyl glucuronide, cause toll like receptor 4 (TLR4)-dependent signaling in vitro and enhanced pain in vivo. Steroid hormones, including estrogens and corticosterone, are also metabolized through glucuronidation. Here we demonstrate that in silico docking predicts that corticosterone, corticosterone-21-glucuronide, estradiol, estradiol-3-glucuronide and estradiol-17-glucuronide all dock with the MD-2 component of the TLR4 receptor complex. In addition to each docking with MD-2, the docking of each was altered by pre-docking with (+)-naloxone, a TLR4 signaling inhibitor. As agonist versus antagonist activity cannot be determined from these in silico interactions, an in vitro study was undertaken to clarify which of these compounds can act in an agonist fashion. Studies using a cell line transfected with TLR4, necessary co-signaling molecules, and a reporter gene revealed that only estradiol-3-glucuronide and estradiol-17-glucuronide increased reporter gene product, indicative of TLR4 agonism. Finally, in in vivo studies, each of the 5 drugs was injected intrathecally at equimolar doses. In keeping with the in vitro results, only estradiol-3-glucuronide and estradiol-17-glucuronide caused enhanced pain. For both compounds, pain enhancement was blocked by the TLR4 antagonist lipopolysaccharide from Rhodobacter sphaeroides, evidence for the involvement in TLR4 in the resultant pain enhancement. These findings have implications for several chronic pain conditions, including migraine and temporomandibular joint disorder, in which pain episodes are more likely in cycling females when estradiol is decreasing and estradiol metabolites are at their highest. (C) 2014 Elsevier Inc. All rights reserved.
C1 [Lewis, Susannah S.; Zhang, Yingning; Maier, Steven F.; Watkins, Linda R.] Univ Colorado, Dept Psychol & Neurosci, Boulder, CO 80309 USA.
[Frick, Morin M.; Sammakia, Tarek] Univ Colorado, Dept Chem & Biochem, Boulder, CO 80309 USA.
[Hutchinson, Mark R.] Univ Adelaide, Sch Med Sci, Discipline Physiol, Adelaide, SA, Australia.
[Rice, Kenner C.] NIDA, Chem Biol Res Branch, NIH, Rockville, MD USA.
[Rice, Kenner C.] NIAAA, NIH, Rockville, MD 20852 USA.
RP Lewis, SS (reprint author), Univ Colorado, Dept Psychol, Campus Box 345, Boulder, CO 80309 USA.
EM susannah.lewis@colorado.edu
OI Hutchinson, Mark/0000-0003-2154-5950
FU NIH [DA023132, DA024044, DE017782]; NIH of NIDA; NIH of National
Institute on Alcohol Abuse and Alcoholism; Colorado Bioscience Discovery
Evaluation Grant Program
FX This work was supported in part by NIH Grants DA023132, DA024044, and
DE017782. This work was also supported in part by the NIH Intramural
Research Programs of NIDA and National Institute on Alcohol Abuse and
Alcoholism and the Colorado Bioscience Discovery Evaluation Grant
Program. Mark R. Hutchinson is a NHMRC CJ Martin Fellow (ID 465423;
2007-2010) and an Australian Research Council Research Fellow
(DP110100297). We thank Dr. Kirk Johnson from Avigen for the gift of the
HEK-TLR4 cell line.
NR 42
TC 4
Z9 4
U1 0
U2 5
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0889-1591
EI 1090-2139
J9 BRAIN BEHAV IMMUN
JI Brain Behav. Immun.
PD FEB
PY 2015
VL 44
BP 128
EP 136
DI 10.1016/j.bbi.2014.09.004
PG 9
WC Immunology; Neurosciences
SC Immunology; Neurosciences & Neurology
GA CQ4RS
UT WOS:000360592900016
PM 25218902
ER
PT J
AU Kobayashi, H
AF Kobayashi, H.
TI Near infrared photoimmunotherapy: basis, applications, and beyond
SO JOURNAL OF NUCLEAR MEDICINE
LA English
DT Meeting Abstract
CT AACR/SNMMI Conference on State-of-the-Art Molecular Imaging in Cancer
Biology and Therapy
CY FEB 11-14, 2015
CL San Diego, CA
SP Amer Assoc Canc Res, Soc Nucl Med & Mol Imaging
C1 [Kobayashi, H.] NCI, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 2
PU SOC NUCLEAR MEDICINE INC
PI RESTON
PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA
SN 0161-5505
EI 1535-5667
J9 J NUCL MED
JI J. Nucl. Med.
PD FEB 1
PY 2015
VL 56
IS 2
SU 1
MA 34
BP 11
EP 12
PG 2
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA CP5PH
UT WOS:000359935300035
ER
PT J
AU Nguyen, V
Panyutin, IV
Neumann, RD
Panyutin, IG
AF Nguyen, V.
Panyutin, I. V.
Neumann, R. D.
Panyutin, I. G.
TI A genomic study of alteration events caused by ionizing radiation in
human embryonic stem cells via next-generation sequencing.
SO JOURNAL OF NUCLEAR MEDICINE
LA English
DT Meeting Abstract
CT AACR/SNMMI Conference on State-of-the-Art Molecular Imaging in Cancer
Biology and Therapy
CY FEB 11-14, 2015
CL San Diego, CA
SP Amer Assoc Canc Res, Soc Nucl Med & Mol Imaging
C1 [Nguyen, V.; Panyutin, I. V.; Neumann, R. D.; Panyutin, I. G.] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU SOC NUCLEAR MEDICINE INC
PI RESTON
PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA
SN 0161-5505
EI 1535-5667
J9 J NUCL MED
JI J. Nucl. Med.
PD FEB 1
PY 2015
VL 56
IS 2
SU 1
MA 42
BP 14
EP 14
PG 1
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA CP5PH
UT WOS:000359935300043
ER
PT J
AU Schnermann, MJ
Nani, RR
Gorka, AP
AF Schnermann, M. J.
Nani, R. R.
Gorka, A. P.
TI Near-IR uncaging chemistry: discovery and applications.
SO JOURNAL OF NUCLEAR MEDICINE
LA English
DT Meeting Abstract
CT AACR/SNMMI Conference on State-of-the-Art Molecular Imaging in Cancer
Biology and Therapy
CY FEB 11-14, 2015
CL San Diego, CA
SP Amer Assoc Canc Res, Soc Nucl Med & Mol Imaging
C1 [Schnermann, M. J.; Nani, R. R.; Gorka, A. P.] NCI, Frederick, MD 21701 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SOC NUCLEAR MEDICINE INC
PI RESTON
PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA
SN 0161-5505
EI 1535-5667
J9 J NUCL MED
JI J. Nucl. Med.
PD FEB 1
PY 2015
VL 56
IS 2
SU 1
MA 53
BP 17
EP 17
PG 1
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA CP5PH
UT WOS:000359935300054
ER
PT J
AU Swenson, R
Bhattacharyya, F
Blackman, B
Coble, V
Lane, K
Li, C
Opina, A
Sail, D
Shi, ZD
Vasalatiy, O
Wu, H
Xu, B
Zhang, X
Krishna, M
Mitchell, J
AF Swenson, R.
Bhattacharyya, F.
Blackman, B.
Coble, V.
Lane, K.
Li, C.
Opina, A.
Sail, D.
Shi, Z. -D.
Vasalatiy, O.
Wu, H.
Xu, B.
Zhang, X.
Krishna, M.
Mitchell, J.
TI The Imaging Probe Development Center makes all types of diagnostic
imaging agents.
SO JOURNAL OF NUCLEAR MEDICINE
LA English
DT Meeting Abstract
CT AACR/SNMMI Conference on State-of-the-Art Molecular Imaging in Cancer
Biology and Therapy
CY FEB 11-14, 2015
CL San Diego, CA
SP Amer Assoc Canc Res, Soc Nucl Med & Mol Imaging
C1 [Swenson, R.; Bhattacharyya, F.; Blackman, B.; Coble, V.; Lane, K.; Li, C.; Opina, A.; Sail, D.; Shi, Z. -D.; Vasalatiy, O.; Wu, H.; Xu, B.; Zhang, X.; Krishna, M.; Mitchell, J.] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SOC NUCLEAR MEDICINE INC
PI RESTON
PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA
SN 0161-5505
EI 1535-5667
J9 J NUCL MED
JI J. Nucl. Med.
PD FEB 1
PY 2015
VL 56
IS 2
SU 1
MA 57
BP 19
EP 19
PG 1
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA CP5PH
UT WOS:000359935300058
ER
PT J
AU Broker, J
Schindeldecker, B
Guzmann, R
Weissgerber, P
Schwarz, Y
Dietrich, A
Birnbaumer, L
Flockerzi, V
Mathar, I
Bruns, D
Freichel, M
AF Broeker, J.
Schindeldecker, B.
Guzmann, R.
Weissgerber, P.
Schwarz, Y.
Dietrich, A.
Birnbaumer, L.
Flockerzi, V.
Mathar, I.
Bruns, D.
Freichel, M.
TI Functional analysis of TRPC1/TRPC4/TRPC5 channel proteins in the
hippocampus
SO NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
LA English
DT Meeting Abstract
CT 81st Annual Meeting of the
Deutsche-Gesellschaft-fur-Experimentelle-und-Klinische-Pharmakologie-und
-Toxikologie-e-V
CY MAR 10-12, 2015
CL Kiel, GERMANY
SP Deutsch Gesell Experimentelle & Klinische Pharmakologie & Pharmakologie e V
C1 [Broeker, J.; Mathar, I.; Freichel, M.] Heidelberg Univ, Inst Pharmakol, D-69115 Heidelberg, Germany.
[Schindeldecker, B.; Guzmann, R.; Schwarz, Y.; Bruns, D.] Univ Saarland, Mol Neurophysiol, Homburg, Germany.
[Weissgerber, P.; Flockerzi, V.] Univ Saarland, Expt & Klin Pharmakol & Toxikol, Homburg, Germany.
[Dietrich, A.] Univ Munich, Walther Straub Inst Pharmakol & Toxikol, D-80539 Munich, Germany.
[Birnbaumer, L.] NIH, Neurobiol Lab, Transmembrane Signaling Grp, Res Triangle Pk, NC USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0028-1298
EI 1432-1912
J9 N-S ARCH PHARMACOL
JI Naunyn-Schmiedebergs Arch. Pharmacol.
PD FEB
PY 2015
VL 388
SU 1
MA 058
BP S16
EP S16
PG 1
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA CP0AV
UT WOS:000359539100059
ER
PT J
AU Londono, JEC
Tian, Q
Hammer, K
Londono, JC
Reil, J
Oberhofer, M
Mannebach, S
Mathar, I
Philipp, S
Tabellion, W
Schwede, F
Dietrich, A
Kastner, L
Laufs, U
Birnbaumer, L
Flockerzi, V
Lipp, P
Freichel, M
AF Londono, Camacho J. E.
Tian, Q.
Hammer, K.
Londono, Camacho J.
Reil, J.
Oberhofer, M.
Mannebach, S.
Mathar, I
Philipp, S.
Tabellion, W.
Schwede, F.
Dietrich, A.
Kaestner, L.
Laufs, U.
Birnbaumer, L.
Flockerzi, V
Lipp, P.
Freichel, M.
TI The development of cardiac hypertrophy is critically regulated by a
Background Ca2+ Entry (BGCE) pathway mediated by TRPC1/TRPC4
SO NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
LA English
DT Meeting Abstract
CT 81st Annual Meeting of the
Deutsche-Gesellschaft-fur-Experimentelle-und-Klinische-Pharmakologie-und
-Toxikologie-e-V
CY MAR 10-12, 2015
CL Kiel, GERMANY
SP Deutsch Gesell Experimentelle & Klinische Pharmakologie & Pharmakologie e V
C1 [Londono, Camacho J. E.; Mathar, I; Freichel, M.] Heidelberg Univ, Pharmakol Inst, D-69115 Heidelberg, Germany.
[Londono, Camacho J. E.; Freichel, M.] DZHK German Ctr Cardiovasc Res, Berlin, Germany.
[Tian, Q.; Hammer, K.; Oberhofer, M.; Tabellion, W.; Kaestner, L.; Lipp, P.] Univ Saarland, Inst Mol Zellbiol, Homburg, Germany.
[Londono, Camacho J.; Mannebach, S.; Philipp, S.; Flockerzi, V] Univ Saarland, Expt & Klin Pharmakol & Toxikol, Homburg, Germany.
[Reil, J.; Laufs, U.] Univ Saarland, Innere Med 3, Homburg, Germany.
[Schwede, F.] Univ Regensburg, Inst Physiol, D-93053 Regensburg, Germany.
[Dietrich, A.] Univ Munich, Walther Straub Inst Pharmakol & Toxikol, D-80539 Munich, Germany.
[Birnbaumer, L.] NIEHS, Transmembrane Signaling Grp, Res Triangle Pk, NC 27709 USA.
RI Kaestner, Lars/P-6988-2016
NR 0
TC 0
Z9 0
U1 0
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0028-1298
EI 1432-1912
J9 N-S ARCH PHARMACOL
JI Naunyn-Schmiedebergs Arch. Pharmacol.
PD FEB
PY 2015
VL 388
SU 1
MA 132
BP S33
EP S33
PG 1
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA CP0AV
UT WOS:000359539100133
ER
PT J
AU Hong, B
Le Gallo, M
Bell, DW
AF Hong, Bo
Le Gallo, Matthieu
Bell, Daphne W.
TI The mutational landscape of endometrial cancer
SO CURRENT OPINION IN GENETICS & DEVELOPMENT
LA English
DT Article
ID UTERINE SEROUS CARCINOMA; GERMLINE PTEN MUTATIONS; TUMOR TYPES;
MICROSATELLITE INSTABILITY; GENES; IDENTIFICATION; SIGNATURES; POLE
AB Globally, endometrial carcinoma causes about 74000 deaths annually. Endometrial carcinomas can be classified into several histological subtypes including endometrioid and serous histologies. Over the course of the past two years, a number of studies have decoded the exomes of endometrioid and serous endometrial carcinomas revealing novel somatically mutated genes that are likely to drive their development. Moreover, an integrated genomic analysis of these two histological subtypes by The Cancer Genome Atlas has led to their molecular reclassification into four discrete molecular subgroups. Collectively, these genomic advances set the stage for future biological and clinical studies to determine their relevance for patient care.
C1 [Hong, Bo; Le Gallo, Matthieu; Bell, Daphne W.] NHGRI, Canc Genet & Comparat Genom Branch, NIH, Bethesda, MD 20892 USA.
RP Bell, DW (reprint author), NHGRI, Canc Genet & Comparat Genom Branch, NIH, Bethesda, MD 20892 USA.
EM belldaph@mail.nih.gov
FU Intramural Research Program of the National Human Genome Research
Institute at NIH
FX All authors are funded by the Intramural Research Program of the
National Human Genome Research Institute at NIH.
NR 36
TC 11
Z9 11
U1 0
U2 3
PU CURRENT BIOLOGY LTD
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0959-437X
EI 1879-0380
J9 CURR OPIN GENET DEV
JI Curr. Opin. Genet. Dev.
PD FEB
PY 2015
VL 30
BP 25
EP 31
DI 10.1016/j.gde.2014.12.004
PG 7
WC Cell Biology; Genetics & Heredity
SC Cell Biology; Genetics & Heredity
GA CM1KL
UT WOS:000357439700004
PM 25622247
ER
PT J
AU Musci, RJ
Masyn, KE
Uhl, G
Maher, B
Kellam, SG
Ialongo, NS
AF Musci, Rashelle J.
Masyn, Katherine E.
Uhl, George
Maher, Brion
Kellam, Sheppard G.
Ialongo, Nicholas S.
TI Polygenic Score x Intervention Moderation: An application of
discrete-time survival analysis to modeling the timing of first tobacco
use among urban youth
SO DEVELOPMENT AND PSYCHOPATHOLOGY
LA English
DT Article
ID ANTISOCIAL PERSONALITY-DISORDER; RANDOMIZED CONTROLLED-TRIAL; SUBSTANCE
USE DISORDERS; DIFFERENTIAL SUSCEPTIBILITY; NICOTINE DEPENDENCE;
SMOKING-CESSATION; ELEMENTARY-SCHOOL; MARIJUANA USE; PREVENTIVE
INTERVENTIONS; ENVIRONMENTAL-INFLUENCES
AB The present study examines the interaction between a polygenic score and an elementary school-based universal preventive intervention trial. The polygenic score reflects the contribution of multiple genes and has been shown in prior research to be predictive of smoking cessation and tobacco use (Uhl et al., 2014). Using data from a longitudinal preventive intervention study, we examined age of first tobacco use from sixth grade to age 18. Genetic data were collected during emerging adulthood and were genotyped using the Affymetrix 6.0 microarray. The polygenic score was computed using these data. Discrete-time survival analysis was employed to test for intervention main and interaction effects with the polygenic score. We found a main effect of the intervention, with the intervention participants reporting their first cigarette smoked at an age significantly later than controls. We also found an Intervention x Polygenic Score interaction, with participants at the higher end of the polygenic score benefitting the most from the intervention in terms of delayed age of first use. These results are consistent with Belsky and colleagues' (e.g., Belsky, Bakermans-Kranenburg, & van IJzendoorn, 2007; Belsky & Pleuss, 2009, 2013; Ellis, Boyce, Belsky, Bakermans-Kranenburg, & van IJzendoorn, 2011) differential susceptibility hypothesis and the concept of for better or worse, wherein the expression of genetic variants are optimally realized in the context of an enriched environment, such as provided by a preventive intervention.
C1 [Musci, Rashelle J.; Maher, Brion; Kellam, Sheppard G.; Ialongo, Nicholas S.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA.
[Masyn, Katherine E.] Harvard Univ, Grad Sch Educ, Cambridge, MA 02138 USA.
[Uhl, George] NIDA, NIH, IRP, Mol Neurobiol Branch, Bethesda, MD 20892 USA.
RP Musci, RJ (reprint author), Johns Hopkins Univ, Dept Mental Hlth, Bloomberg Sch Publ Hlth, 624 North Broadway, Baltimore, MD 21205 USA.
EM rmusci@jhsph.edu
FU National Institute of Mental Health [MH57005, T32 MH18834]; National
Institute on Drug Abuse [NIDA R37 DA11796]
FX This research was supported by Grants MH57005 and T32 MH18834 from the
National Institute of Mental Health (to N.S.I.) and Grant NIDA R37
DA11796 from the National Institute on Drug Abuse (to N.S.I.).
NR 88
TC 2
Z9 3
U1 5
U2 10
PU CAMBRIDGE UNIV PRESS
PI NEW YORK
PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA
SN 0954-5794
EI 1469-2198
J9 DEV PSYCHOPATHOL
JI Dev. Psychopathol.
PD FEB
PY 2015
VL 27
IS 1
SI SI
BP 111
EP 122
DI 10.1017/S0954579414001333
PG 12
WC Psychology, Developmental
SC Psychology
GA CH5WL
UT WOS:000354106300009
PM 25640834
ER
PT J
AU Nussinov, R
Tsai, CJ
AF Nussinov, Ruth
Tsai, Chung-Jung
TI Allostery without a conformational change? Revisiting the paradigm
SO CURRENT OPINION IN STRUCTURAL BIOLOGY
LA English
DT Article
ID CATABOLITE ACTIVATOR PROTEIN; CAP-DNA COMPLEX; ENERGY LANDSCAPES;
COUPLED RECEPTOR; BINDING CASCADES; STRUCTURAL BASIS; PLAUSIBLE MODEL;
HEMOGLOBIN; MECHANISM; DYNAMICS
AB Classically, allostery induces a functional switch through a conformational change. However, lately an increasing number of studies concluded that the allostery they observe takes place through sheer dynamics. Here we explain that even if a structural comparison between the active and inactive states does not detect a conformational change, it does not mean that there is no conformational change. We list likely reasons for this lack of observation, including crystallization conditions and crystal effects; one of the states is disordered; the structural comparisons disregard the quaternary protein structure; overlooking synergy effects among allosteric effectors and graded incremental switches and too short molecular dynamics simulations. Specific functions are performed by distinct conformations; they emerge through specific interactions between conformationally selected states.
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 Sch Med, Dept Human Genet & Mol Med, Sackler Inst 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; National Institutes of Health
[HHSN261200800001E]; Intramural Research Program of the NIH, National
Cancer Institute, Center for Cancer Research
FX This project has been funded in whole or in part with Federal funds from
the National Cancer Institute, National Institutes of Health, under
contract 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 NIH, National Cancer Institute, Center for Cancer Research.
NR 65
TC 38
Z9 39
U1 6
U2 34
PU CURRENT BIOLOGY LTD
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0959-440X
EI 1879-033X
J9 CURR OPIN STRUC BIOL
JI Curr. Opin. Struct. Biol.
PD FEB
PY 2015
VL 30
BP 17
EP 24
DI 10.1016/j.sbi.2014.11.005
PG 8
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA CI2PF
UT WOS:000354588800005
PM 25500675
ER
PT J
AU Fang, XY
Stagno, JR
Bhandari, YR
Zuo, XB
Wang, YX
AF Fang, Xianyang
Stagno, Jason R.
Bhandari, Yuba R.
Zuo, Xiaobing
Wang, Yun-Xing
TI Small-angle X-ray scattering: a bridge between RNA secondary structures
and three-dimensional topological structures
SO CURRENT OPINION IN STRUCTURAL BIOLOGY
LA English
DT Article
ID REV-RESPONSE ELEMENT; TIME-RESOLVED SAXS; BIOLOGICAL MACROMOLECULES;
MOLECULAR-STRUCTURE; SHAPE DETERMINATION; RESOLUTION; PROTEIN; COMPLEX;
BINDING; HIV-1
AB Whereas the structures of small to medium-sized well folded RNA molecules often can be determined by either X-ray crystallography or NMR spectroscopy, obtaining structural information for large RNAs using experimental, computational, or combined approaches remains a major interest and challenge. RNA is very sensitive to small-angle X-ray scattering (SAXS) due to high electron density along phosphate-sugar backbones, whose scattering contribution dominates SAXS intensity. For this reason, SAXS is particularly useful in obtaining global RNA structural information that outlines backbone topologies and, therefore, molecular envelopes. Such information is extremely valuable in bridging the gap between the secondary structures and three-dimensional topological structures of RNA molecules, particularly those that have proven difficult to study using other structure-determination methods. Here we review published results of RNA topological structures derived from SAXS data or in combination with other experimental data, as well as details on RNA sample preparation for SAXS experiments.
C1 [Fang, Xianyang; Wang, Yun-Xing] Natl Canc Inst, NCI Small Angle Xray Scattering Core Facil, Struct Biophys Lab, NIH, Rockville, MD 20850 USA.
[Stagno, Jason R.; Bhandari, Yuba R.; Wang, Yun-Xing] Natl Canc Inst, Prot Nucle Acid Interact Sect, Struct Biophys Lab, NIH, Rockville, MD USA.
[Zuo, Xiaobing] Argonne Natl Lab, Adv Photon Source, Argonne, IL 60439 USA.
RP Wang, YX (reprint author), Natl Canc Inst, NCI Small Angle Xray Scattering Core Facil, Struct Biophys Lab, NIH, Rockville, MD 20850 USA.
EM wangyunx@mail.nih.gov
OI Zuo, Xiaobing/0000-0002-0134-4804
FU Intramural Research Program of the National Institutes of Health,
National Cancer Institute (NCI) Center for Cancer Research; U.S. DOE
[DE-AC02-06CH11357]; NCI [PUP-77]; Argonne National Laboratory [PUP-77]
FX We sincerely thank David Lilley, Samuel Butcher, Marc Jamin, Norman
Pace, Alexei Kazanstev, Ajaykumar Gopal and William Gelbart for
providing materials for figures. This work was supported by the
Intramural Research Program of the National Institutes of Health,
National Cancer Institute (NCI) Center for Cancer Research. Use of the
Advanced Photon Source, an Office of Science User Facility operated for
the U.S. Department of Energy (DOE) Office of Science by Argonne
National Laboratory, was supported by the U.S. DOE under contract no.
DE-AC02-06CH11357 and by NCI under the PUP-77 Agreement between NCI and
Argonne National Laboratory.
NR 94
TC 7
Z9 7
U1 1
U2 21
PU CURRENT BIOLOGY LTD
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0959-440X
EI 1879-033X
J9 CURR OPIN STRUC BIOL
JI Curr. Opin. Struct. Biol.
PD FEB
PY 2015
VL 30
BP 147
EP 160
DI 10.1016/j.sbi.2015.02.010
PG 14
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA CI2PF
UT WOS:000354588800019
PM 25765781
ER
PT J
AU Bolnick, AD
Bolnick, JM
Singh, M
Fritz, R
Kilburn, BA
Simmerman, N
Drewlo, S
Diamond, MP
Armant, DR
AF Bolnick, Alan D.
Bolnick, Jay M.
Singh, Manvinder
Fritz, Rani
Kilburn, Brian A.
Simmerman, Neil
Drewlo, Sascha
Diamond, Michael P.
Armant, D. Randall
TI Trophoblast Retrieval and Isolation from the Cervix (TRIC) for
Non-Invasive First Trimester Fetal Gender Determination in a Carrier of
Congenital Adrenal Hyperplasia
SO FERTILITY AND STERILITY
LA English
DT Meeting Abstract
CT 63rd Annual Meeting of the Pacific-Coast-Reproductive-Society (PCRS) on
Building Connections, Achieving Excellence
CY MAR 11-15, 2015
CL Rancho Mirage, CA
SP Pacific Coast Reprod Soc
C1 [Bolnick, Alan D.; Bolnick, Jay M.; Singh, Manvinder; Fritz, Rani; Kilburn, Brian A.; Simmerman, Neil; Drewlo, Sascha; Armant, D. Randall] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA.
[Armant, D. Randall] Wayne State Univ, Sch Med, Dept Anat & Cell Biol, Detroit, MI 48201 USA.
[Diamond, Michael P.] Georgia Regents Univ, Dept Obstet & Gynecol, Augusta, GA USA.
[Armant, D. Randall] NICHD, Program Reprod & Adult Endocrinol, NIH, DHHS, Bethesda, MD 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 0015-0282
EI 1556-5653
J9 FERTIL STERIL
JI Fertil. Steril.
PD FEB
PY 2015
VL 103
IS 2
SU S
MA P-10
BP E13
EP E13
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA CH2GJ
UT WOS:000353843400019
ER
PT J
AU Bolnick, AD
Bolnick, JM
Kilburn, BA
Barrak, C
Jain, C
Singhi, P
Diamond, MP
Armant, DR
AF Bolnick, Alan D.
Bolnick, Jay M.
Kilburn, Brian A.
Barrak, Charbel
Jain, Chandni
Singhi, Pooja
Diamond, Michael P.
Armant, D. Randall
TI Clarifying the Role of MAP Kinases in the Molecular Pathway That
Regulates HBEGF Mobilization for Trophoblast Survival at Low O-2 during
the First Trimester of Pregnancy
SO FERTILITY AND STERILITY
LA English
DT Meeting Abstract
CT 63rd Annual Meeting of the Pacific-Coast-Reproductive-Society (PCRS) on
Building Connections, Achieving Excellence
CY MAR 11-15, 2015
CL Rancho Mirage, CA
SP Pacific Coast Reprod Soc
C1 [Bolnick, Alan D.; Bolnick, Jay M.; Kilburn, Brian A.; Barrak, Charbel; Jain, Chandni; Singhi, Pooja; Armant, D. Randall] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA.
[Armant, D. Randall] Wayne State Univ, Sch Med, Dept Anat & Cell Biol, Detroit, MI 48201 USA.
[Diamond, Michael P.] Georgia Regents Univ, Dept Obstet & Gynecol, Augusta, GA USA.
[Armant, D. Randall] NICHD, Program Reprod & Adult Endocrinol, NIH, DHHS, Bethesda, MD 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 0015-0282
EI 1556-5653
J9 FERTIL STERIL
JI Fertil. Steril.
PD FEB
PY 2015
VL 103
IS 2
SU S
MA P-11
BP E13
EP E13
PG 1
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA CH2GJ
UT WOS:000353843400020
ER
PT J
AU Lim, JA
Li, LS
Kakhlon, O
Myerowitz, R
Raben, N
AF Lim, Jeong-A
Li, Lishu
Kakhlon, Or
Myerowitz, Rachel
Raben, Nina
TI Defects in calcium homeostasis and mitochondria can be reversed in Pompe
disease
SO AUTOPHAGY
LA English
DT Article
DE autophagy; calcium; lysosome; mitochondria; mitophagy; Pompe disease
ID LYSOSOMAL STORAGE DISEASE; APOPTOSIS-INDUCING FACTOR; ACID MALTASE
DEFICIENCY; KINASE KINASE-BETA; SKELETAL-MUSCLE; MOUSE MODEL;
AUTOPHAGOSOME FORMATION; DAMAGED MITOCHONDRIA; OXIDATIVE STRESS;
CLINICAL-TRIALS
AB Mitochondria-induced oxidative stress and flawed autophagy are common features of neurodegenerative and lysosomal storage diseases (LSDs). Although defective autophagy is particularly prominent in Pompe disease, mitochondrial function has escaped examination in this typical LSD. We have found multiple mitochondrial defects in mouse and human models of Pompe disease, a life-threatening cardiac and skeletal muscle myopathy: a profound dysregulation of Ca2+ homeostasis, mitochondrial Ca2+ overload, an increase in reactive oxygen species, a decrease in mitochondrial membrane potential, an increase in caspase-independent apoptosis, as well as a decreased oxygen consumption and ATP production of mitochondria. In addition, gene expression studies revealed a striking upregulation of the beta 1 subunit of L-type Ca2+ channel in Pompe muscle cells. This study provides strong evidence that disturbance of Ca2+ homeostasis and mitochondrial abnormalities in Pompe disease represent early changes in a complex pathogenetic cascade leading from a deficiency of a single lysosomal enzyme to severe and hard-to-treat autophagic myopathy. Remarkably, L-type Ca2+ channel blockers, commonly used to treat other maladies, reversed these defects, indicating that a similar approach can be beneficial to the plethora of lysosomal and neurodegenerative disorders.
C1 [Lim, Jeong-A; Li, Lishu; Myerowitz, Rachel; Raben, Nina] NIAMSD, Lab Muscle Stem Cells & Gene Regulat, NIH, Bethesda, MD 20892 USA.
[Kakhlon, Or] Hadassah Hebrew Univ, Med Ctr, Dept Neurol, Jerusalem, Israel.
[Myerowitz, Rachel] St Marys Coll Maryland, St Marys City, MD 20686 USA.
RP Raben, N (reprint author), NIAMSD, Lab Muscle Stem Cells & Gene Regulat, NIH, Bethesda, MD 20892 USA.
EM rabenn@mail.nih.gov
RI Li, Lishu /J-3191-2015
FU Intramural Research Program of the National Institute of Arthritis and
Musculoskeletal and Skin diseases of the National Institutes of Health;
CRADA; Acid Maltase Deficiency Association
FX This research was supported in part by the Intramural Research Program
of the National Institute of Arthritis and Musculoskeletal and Skin
diseases of the National Institutes of Health. Dr. Lim and Dr. Li are
supported in part by a CRADA between NIH and Genzyme Corporation and
from the Acid Maltase Deficiency Association.
NR 95
TC 8
Z9 8
U1 1
U2 5
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 1554-8627
EI 1554-8635
J9 AUTOPHAGY
JI Autophagy
PD FEB
PY 2015
VL 11
IS 2
BP 385
EP 402
DI 10.1080/15548627.2015.1009779
PG 18
WC Cell Biology
SC Cell Biology
GA CF8AX
UT WOS:000352778700016
PM 25758767
ER
PT J
AU Federoff, M
Schottlaender, LV
Houlden, H
Singleton, A
AF Federoff, Monica
Schottlaender, Lucia V.
Houlden, Henry
Singleton, Andrew
TI Multiple system atrophy: the application of genetics in understanding
etiology
SO CLINICAL AUTONOMIC RESEARCH
LA English
DT Review
DE Genome-wide association; Linkage analysis; Genetic risk; Mutation
ID PROGRESSIVE SUPRANUCLEAR PALSY; MYOTONIC-DYSTROPHY TYPE-2;
COPY-NUMBER-VARIATION; ALPHA-SYNUCLEIN GENE;
AMYOTROPHIC-LATERAL-SCLEROSIS; GLIAL CYTOPLASMIC INCLUSIONS; FAMILIAL
PARKINSONS-DISEASE; TRANSGENIC MOUSE MODEL; REVEALS NO ASSOCIATION;
MICROGLIAL ACTIVATION
AB Classically defined phenotypically by a triad of cerebellar ataxia, parkinsonism, and autonomic dysfunction in conjunction with pyramidal signs, multiple system atrophy (MSA) is a rare and progressive neurodegenerative disease affecting an estimated 3-4 per every 100,000 individuals among adults 50-99 years of age. With a pathological hallmark of alpha-synuclein-immunoreactive glial cytoplasmic inclusions (GCIs; Papp-Lantos inclusions), MSA patients exhibit marked neurodegenerative changes in the striatonigral and/or olivopontocerebellar structures of the brain. As a member of the alpha-synucleinopathy family, which is defined by its well-demarcated alpha-synuclein-immunoreactive inclusions and aggregation, MSA's clinical presentation exhibits several overlapping features with other members including Parkinson's disease (PD) and dementia with Lewy bodies (DLB). Given the extensive fund of knowledge regarding the genetic etiology of PD revealed within the past several years, a genetic investigation of MSA is warranted. While a current genome-wide association study is underway for MSA to further clarify the role of associated genetic loci and single-nucleotide polymorphisms, several cases have presented solid preliminary evidence of a genetic etiology. Naturally, genes and variants manifesting known associations with PD (and other phenotypically similar neurodegenerative disorders), including SNCA and MAPT, have been comprehensively investigated in MSA patient cohorts. More recently variants in COQ2 have been linked to MSA in the Japanese population although this finding awaits replication. Nonetheless, significant positive associations with subsequent independent replication studies have been scarce. With very limited information regarding genetic mutations or alterations in gene dosage as a cause of MSA, the search for novel risk genes, which may be in the form of common variants or rare variants, is the logical nexus for MSA research. We believe that the application of next generation genetic methods to MSA will provide valuable insight into the underlying causes of this disease, and will be central to the identification of etiologic-based therapies.
C1 [Federoff, Monica; Singleton, Andrew] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
[Federoff, Monica; Schottlaender, Lucia V.; Houlden, Henry] UCL Inst Neurol, Dept Mol Neurosci, London WC1N 3BG, England.
RP Singleton, A (reprint author), NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
EM h.houlden@ion.ucl.ac.uk; singleta@mail.nih.gov
RI Singleton, Andrew/C-3010-2009; Houlden, Henry/C-1532-2008
OI Houlden, Henry/0000-0002-2866-7777
FU National Institute on Aging, National Institutes of Health, Department
of Health and Human Services [ZO1 AG000958]
FX The authors work is supported in part by the Intramural Research Program
of the National Institute on Aging, National Institutes of Health,
Department of Health and Human Services; project ZO1 AG000958.
NR 150
TC 0
Z9 1
U1 1
U2 5
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 0959-9851
EI 1619-1560
J9 CLIN AUTON RES
JI Clin. Auton. Res.
PD FEB
PY 2015
VL 25
IS 1
SI SI
BP 19
EP 36
DI 10.1007/s10286-014-0267-5
PG 18
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA CG4VW
UT WOS:000353286500004
PM 25687905
ER
PT J
AU Goldstein, DS
Kopin, IJ
Sharabi, Y
Holmes, C
AF Goldstein, David S.
Kopin, Irwin J.
Sharabi, Yehonatan
Holmes, Courtney
TI Plasma biomarkers of decreased vesicular storage distinguish Parkinson
disease with orthostatic hypotension from the parkinsonian form of
multiple system atrophy
SO CLINICAL AUTONOMIC RESEARCH
LA English
DT Article
DE Parkinson disease; Biomarker; Multiple system atrophy; Orthostatic
hypotension; Autonomic; Sympathetic; Fluorodopamine
ID CARDIAC SYMPATHETIC INNERVATION; CATECHOLS; HUMANS
AB Parkinson disease with orthostatic hypotension (PD + OH) and the parkinsonian form of multiple system atrophy (MSA-P) can be difficult to distinguish clinically. Recent studies indicate that PD entails a vesicular storage defect in catecholaminergic neurons. Although cardiac sympathetic neuroimaging by F-18-dopamine positron emission tomography can identify decreased vesicular storage, this testing is not generally available. We assessed whether plasma biomarkers of a vesicular storage defect can separate PD + OH from MSA-P.
We conceptualized that after F-dopamine injection, augmented production of F-dihydroxyphenylacetic acid (F-DOPAC) indicates decreased vesicular storage, and we therefore predicted that arterial plasma F-DOPAC would be elevated in PD + OH but not in MSA-P. We measured arterial plasma F-DOPAC after F-18-dopamine administration (infused i.v. over 3 min) in patients with PD + OH (N = 12) or MSA-P (N = 21) and in healthy control subjects (N = 26). Peak F-DOPAC:dihydroxyphenylglycol (DHPG) was also calculated to adjust for effects of denervation on F-DOPAC production.
Plasma F-DOPAC accumulated rapidly after initiation of F-18-dopamine infusion. Peak F-DOPAC (5-10 min) in PD + OH averaged three times that in MSA-P (P < 0.0001). Among MSA-P patients, none had peak F-DOPAC > 300 nCi-kg/cc-mCi, in contrast with 7 of 12 PD + OH patients (chi (2) = 16.6, P < 0.0001). DHPG was lower in PD + OH (3.83 +/- A 0.36 nmol/L) than in MSA-P (5.20 +/- A 0.29 nmol/L, P = 0.007). All MSA-P patients had peak F-DOPAC:DHPG < 60, in contrast with 9 of 12 PD + OH patients (chi (2) = 17.5, P < 0.0001). Adjustment of peak F-DOPAC for DHPG increased test sensitivity from 58 to 81 % at similar high specificity.
After F-dopamine injection, plasma F-DOPAC and F-DOPAC:DHPG distinguish PD + OH from MSA-P.
C1 [Goldstein, David S.; Kopin, Irwin J.; Holmes, Courtney] NINDS, Clin Neurocardiol Sect, NIH, Bethesda, MD 20892 USA.
[Sharabi, Yehonatan] Tel Aviv Univ, Chaim Sheba Med Ctr, Tel Hashomer, Israel.
RP Goldstein, DS (reprint author), NINDS, Clin Neurocardiol Sect, NIH, 10 Ctr Dr MSC-1620,Bldg 10 Room 5N220, Bethesda, MD 20892 USA.
EM goldsteind@ninds.nih.gov
FU NIH, National Institute of Neurological Disorders and Stroke
FX Authors acknowledge the support of the intramural Research Program of
the NIH, National Institute of Neurological Disorders and Stroke.
NR 14
TC 1
Z9 1
U1 0
U2 0
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 0959-9851
EI 1619-1560
J9 CLIN AUTON RES
JI Clin. Auton. Res.
PD FEB
PY 2015
VL 25
IS 1
SI SI
BP 61
EP 67
DI 10.1007/s10286-015-0268-z
PG 7
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA CG4VW
UT WOS:000353286500008
PM 25638582
ER
PT J
AU Wen, L
Shi, YB
AF Wen, Luan
Shi, Yun-Bo
TI Unliganded Thyroid Hormone Receptor alpha Controls Developmental Timing
in Xenopus tropicalis
SO ENDOCRINOLOGY
LA English
DT Article
ID EFFECTOR NUCLEASES TALENS; RETINOIC ACID RECEPTORS; INTESTINAL
STEM-CELLS; IN-VIVO ANALYSIS; AMPHIBIAN METAMORPHOSIS; BETA GENE;
POSTEMBRYONIC DEVELOPMENT; MEDIATED TRANSCRIPTION; LAEVIS METAMORPHOSIS;
HISTONE ACETYLATION
AB Thyroid hormone (T-3) affects adult metabolism and postembryonic development in vertebrates. T-3 functions mainly via binding to its receptors (TRs) to regulate gene expression. There are 2 TR genes, TR alpha and TR beta, with TR alpha more ubiquitously expressed. During development, TR alpha expression appears earlier than T-3 synthesis and secretion into the plasma. This and the ability of TRs to regulate gene expression both in the presence and absence of T-3 have indicated a role for unliganded TR during vertebrate development. On the other hand, it has been difficult to study the role of unliganded TR during development in mammals because of the difficulty to manipulate the uterus-enclosed, late-stage embryos. Here we use amphibian development as a model to address this question. We have designed transcriptional activator-like effector nucleases (TALENs) to mutate the TR alpha gene in Xenopus tropicalis. We show that knockdown of TR alpha enhances tadpole growth in premetamorphic tadpoles, in part because of increased growth hormone gene expression. More importantly, the knockdown also accelerates animal development, with the knockdown animals initiating metamorphosis at a younger age and with a smaller body size. On the other hand, such tadpoles are resistant to exogenous T3 treatment and have delayed natural metamorphosis. Thus, our studies not only have directly demonstrated a critical role of endogenous TR alpha in mediating the metamorphic effect of T-3 but also revealed novel functions of unliganded TR alpha during postembryonic development, that is, regulating both tadpole growth rate and the timing of metamorphosis.
C1 [Wen, Luan; Shi, Yun-Bo] NICHHD, Sect Mol Morphogenesis, Program Cell Regulat & Metab, NIH, Bethesda, MD 20892 USA.
RP Shi, YB (reprint author), NICHHD, Sect Mol Morphogenesis, Program Cell Regulat & Metab, NIH, Bldg 18T,Room 106, Bethesda, MD 20892 USA.
EM shi@helix.nih.gov
FU Eunice Kennedy Shriver National Institute of Child Health; Eunice
Kennedy Shriver National Institute of Child Health and Human
Development, National Institutes of Health
FX This work was supported by the intramural Research Program of The Eunice
Kennedy Shriver National Institute of Child Health and Human
Development, National Institutes of Health.
NR 86
TC 15
Z9 15
U1 2
U2 8
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0013-7227
EI 1945-7170
J9 ENDOCRINOLOGY
JI Endocrinology
PD FEB
PY 2015
VL 156
IS 2
BP 721
EP 734
DI 10.1210/en.2014-1439
PG 14
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA CG2UV
UT WOS:000353131800030
PM 25456066
ER
PT J
AU Burotto, M
Tageja, N
Rosenberg, A
Mahalingam, S
Quezado, M
Velarde, M
Edgerly, M
Fojo, T
AF Burotto, Mauricio
Tageja, Nishant
Rosenberg, Avi
Mahalingam, Sowmya
Quezado, Martha
Velarde, Margarita
Edgerly, Maureen
Fojo, Tito
TI Brain Metastasis in Patients With Adrenocortical Carcinoma: A Clinical
Series
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID CANCER-PATIENTS; MANAGEMENT; RECURRENT; SURVIVAL; UPDATE; CHILD
AB Introduction: Adrenocortical carcinoma (ACC) is a heterogeneous and rare disease. At presentation or at the time of a recurrence, the disease commonly spreads to the liver, lungs, lymph nodes, and bones. The brain has only rarely been reported as a site of metastases.
Objective: The aims of this report were to describe the clinical characteristics of patients with ACC who developed brain metastasis and were evaluated at the National Cancer Institute.
Methods: We describe the history and clinical presentation of six patients with ACC and metastatic disease in the brain. Images of the six patients and pathology slides were reviewed when available.
Results: The median age at the time of the diagnosis of ACC was 42 years. The median time from the initial diagnosis until the presentation of brain metastasis was 43 months. As a group the patients had previously received multiples lines of chemotherapy (median of three), and they presented with one to three metastatic brain lesions. Four patients underwent metastasectomy, one had radiosurgery, and one had both modalities. Two patients are still alive, three died, between 2 and 14 months after the diagnosis of brain metastases, and one was lost to follow-up.
Conclusion: Patients with advanced ACC can rarely present with metastasis to the brain, most often long after the initial diagnosis. Timely diagnosis of brain metastasis with appropriate intervention after discussion in a multidisciplinary meeting can improve the prognosis in this particular scenario.
C1 [Burotto, Mauricio; Tageja, Nishant; Velarde, Margarita; Edgerly, Maureen; Fojo, Tito] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Rosenberg, Avi; Quezado, Martha] NCI, Natl Lab Pathol, NIH, Bethesda, MD 20892 USA.
[Mahalingam, Sowmya] George Washington Univ, Rockville, MD 20852 USA.
RP Burotto, M (reprint author), NCI, Ctr Canc Res, 10 Ctr Dr 12N226, Bethesda, MD 20892 USA.
EM mauricio.burottopichun@nih.gov
OI Rosenberg, Avi/0000-0003-2356-950X
NR 22
TC 1
Z9 1
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0021-972X
EI 1945-7197
J9 J CLIN ENDOCR METAB
JI J. Clin. Endocrinol. Metab.
PD FEB
PY 2015
VL 100
IS 2
BP 331
EP 336
DI 10.1210/jc.2014-2650
PG 6
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA CG5RF
UT WOS:000353350900032
PM 25412413
ER
PT J
AU Raff, H
Auchus, RJ
Findling, JW
Nieman, LK
AF Raff, Hershel
Auchus, Richard J.
Findling, James W.
Nieman, Lynnette K.
TI Urine Free Cortisol in the Diagnosis of Cushing's Syndrome: Is It Worth
Doing and, If So, How?
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Editorial Material
ID TANDEM MASS-SPECTROMETRY; NIGHT SALIVARY CORTISOL; DISCOVERY
C1 [Raff, Hershel] Med Coll Wisconsin, Dept Med, Dept Surg, Milwaukee, WI 53226 USA.
[Raff, Hershel] Med Coll Wisconsin, Dept Physiol, Milwaukee, WI 53226 USA.
[Raff, Hershel] Aurora St Lukes Med Ctr, Endocrine Res Lab, Milwaukee, WI 53215 USA.
[Auchus, Richard J.] Univ Michigan, Dept Internal Med, Div Metab Endocrinol & Diabet, Ann Arbor, MI 48109 USA.
[Findling, James W.] Med Coll Wisconsin, Endocrinol Ctr & Clin, Milwaukee, WI 53226 USA.
[Nieman, Lynnette K.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Program Reprod & Adult Endocrinol, Bethesda, MD 20892 USA.
RP Raff, H (reprint author), Aurora St Lukes Med Ctr, Endocrinol, 2801 West Kinnickinnic River Pkwy,Suite 245, Milwaukee, WI 53215 USA.
EM hraff@mcw.edu
FU Intramural NIH HHS; NIDDK NIH HHS [P30 DK020572]
NR 14
TC 15
Z9 15
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0021-972X
EI 1945-7197
J9 J CLIN ENDOCR METAB
JI J. Clin. Endocrinol. Metab.
PD FEB
PY 2015
VL 100
IS 2
BP 395
EP 397
DI 10.1210/jc.2014-3766
PG 3
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA CG5RF
UT WOS:000353350900039
PM 25423573
ER
PT J
AU Rao, JU
Engelke, UFH
Sweep, FCGJ
Pacak, K
Kusters, B
Goudswaard, AG
Hermus, ARMM
Mensenkamp, AR
Eisenhofer, G
Qin, N
Richter, S
Kunst, HPM
Timmers, HJLM
Wevers, RA
AF Rao, J. U.
Engelke, U. F. H.
Sweep, F. C. G. J.
Pacak, K.
Kusters, B.
Goudswaard, A. G.
Hermus, A. R. M. M.
Mensenkamp, A. R.
Eisenhofer, G.
Qin, N.
Richter, S.
Kunst, H. P. M.
Timmers, H. J. L. M.
Wevers, R. A.
TI Genotype-Specific Differences in the Tumor Metabolite Profile of
Pheochromocytoma and Paraganglioma Using Untargeted and Targeted
Metabolomics
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID PURINE METABOLISM; IN-VIVO; H-1-NMR
AB Context and Objective: Pheochromocytomas and paragangliomas (PGLs) are neuroendocrine tumors of sympathetic or parasympathetic paraganglia. Nearly 40% of PGLs are caused by germline mutations. The present study investigated the effect of genetic alterations on metabolic networks in PGLs.
Design: Homogenates of 32 sporadic PGLs and 48 PGLs from patients with mutations in SDHB, SDHD, SDHAF-2, VHL, RET, and NF-1 were subjected to proton (H-1) nuclear magnetic resonance (NMR) spectroscopy at 500 MHz for untargeted and HPLC tandem mass spectrometry for targeted metabolite profiling.
Results: 1H NMR spectroscopy identified 28 metabolites in PGLs of which 12 showed genotype-specific differences. Part of these results published earlier reported low complex II activity (P < .0001) and low ATP/ADP/AMP content (P < .001) in SDH-related PGLs compared with sporadics and PGLs of other genotypes. Extending these results, low levels of N-acetylaspartic acid (NAA; P < .05) in SDH tumors and creatine (P < .05) in VHL tumors were observed compared with sporadics and other genotypes. Positive correlation was observed between NAA and ATP/ADP/AMP content (P < .001) and NAA and complex II activity (P < .0001) of PGLs. Targeted purine analysis in PGLs showed low adenine in cluster 1 compared with cluster 2 tumors (SDH P < .0001; VHL P < .05) whereas lower levels (P < .05) of guanosine and hypoxanthine were observed in RET tumors compared with SDH tumors. Principal component analysis (PCA) of metabolites could distinguish PGLs of different genotypes.
Conclusions: The present study gives a comprehensive picture of alterations in energy metabolism in SDH- and VHL-related PGLs and establishes the interrelationship of energy metabolism and amino acid and purine metabolism in PGLs.
C1 [Rao, J. U.; Engelke, U. F. H.; Sweep, F. C. G. J.; Goudswaard, A. G.; Wevers, R. A.] Radboud Univ Nijmegen, Lab Genet Endocrine & Metab Dis, Dept Lab Med, Med Ctr, NL-6525 ED Nijmegen, Netherlands.
[Rao, J. U.; Hermus, A. R. M. M.; Timmers, H. J. L. M.] Radboud Univ Nijmegen, Endocrinol Sect, Dept Internal Med, Med Ctr, NL-6525 ED Nijmegen, Netherlands.
[Pacak, K.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA.
[Kusters, B.] Radboud Univ Nijmegen, Med Ctr, Dept Pathol, NL-6525 ED Nijmegen, Netherlands.
[Mensenkamp, A. R.] Radboud Univ Nijmegen, Med Ctr, Dept Genet, NL-6525 ED Nijmegen, Netherlands.
[Eisenhofer, G.; Qin, N.; Richter, S.] Univ Hosp Carl Gustav Carus, Dept Med, Dresden, Germany.
[Eisenhofer, G.; Qin, N.; Richter, S.] Univ Hosp Carl Gustav Carus, Inst Clin Chem & Lab Med, Dresden, Germany.
[Kunst, H. P. M.] Radboud Univ Nijmegen, Dept Otolaryngol, NL-6525 ED Nijmegen, Netherlands.
[Kusters, B.] Maastricht Univ, Med Ctr, Dept Pathol, NL-6200 MD Maastricht, Netherlands.
RP Wevers, RA (reprint author), Radboud Univ Med, Lab Genet Endocrine & Metab Dis, Dept Lab Med, Route 830,Ctr Geert Grootepl 10, NL-6525 GA Nijmegen, Netherlands.
EM ron.wevers@radboudumc.nl
RI Kunst, Henricus/J-6456-2012; Wevers, Ron/H-8116-2014; Hermus,
A.R.M.M./H-8043-2014; Engelke, U.F.H./L-4293-2015; Mensenkamp,
A.R./L-4520-2015; Sweep, C.G.J./H-8096-2014; Kusters, B./L-4465-2015
OI Wevers, Ron/0000-0003-2278-9746;
FU European Union Seventh Framework Programme (FP7) (ENSAT CANCER) [259735]
FX The work leading to these results has received funding from the European
Union Seventh Framework Programme (FP7/2007-2013) under Grant No. 259735
(ENSAT CANCER).
NR 19
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U1 0
U2 7
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0021-972X
EI 1945-7197
J9 J CLIN ENDOCR METAB
JI J. Clin. Endocrinol. Metab.
PD FEB
PY 2015
VL 100
IS 2
BP E214
EP E222
DI 10.1210/jc.2014-2138
PG 9
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA CG5RF
UT WOS:000353350900011
PM 25459911
ER
PT J
AU Reich, A
Bae, AS
Barnes, AM
Cabral, WA
Hinek, A
Stimec, J
Hill, SC
Chitayat, D
Marini, JC
AF Reich, Adi
Bae, Alison S.
Barnes, Aileen M.
Cabral, Wayne A.
Hinek, Aleksander
Stimec, Jennifer
Hill, Suvimol C.
Chitayat, David
Marini, Joan C.
TI Type V OI Primary Osteoblasts Display Increased Mineralization Despite
Decreased COL1A1 Expression
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID IMPERFECTA TYPE-V; OSTEOGENESIS-IMPERFECTA; PHENOTYPIC VARIABILITY;
HYPERPLASTIC CALLUS; IFITM5 MUTATION; I COLLAGEN; DEFICIENCY;
DEPOSITION; SERPINF1; 5'-UTR
AB Context: Patients with type V osteogenesis imperfecta (OI) are heterozygous for a dominant IFITM5c.-14C>T mutation, which adds five residues to the N terminus of bone-restricted inter-feron-induced transmembrane-like protein (BRIL), a transmembrane protein expressed in osteoblasts. Type VOI skeletal findings include hyperplastic callus formation, ossification of the forearm interosseous membrane, and dense metaphyseal bands.
Objective: The objective of this study was to examine the role of osteoblasts in the active mineralization traits of type V OI and the effect of the IFITM5 mutation on type I collagen.
Methods: We identified eight patients with the IFITM5c.-14C>T mutation. Cultured osteoblasts from type V OI patients were used to study osteoblast differentiation and mineralization.
Results: We verified the expression and stability of mutant IFITM5 transcripts. In differentiated type V OI primary osteoblasts in culture, the IFITM5 expression and BRIL level is comparable with control. Both early and late markers of osteoblast differentiation are increased in type V OI osteoblasts. Mineralization, assayed by alizarin red staining, was increased in type V OI osteoblasts compared with control. However, type V OI osteoblasts have significantly decreased COL1A1 transcripts in mid-to late differentiation. Type I collagen protein is concomitantly decreased, with decreased cross-linked collagen in matrix and altered appearance of fibrils deposited in culture.
Conclusions: This study demonstrates that type V OI mineralization has a gain-of-function mechanism at the osteoblast level, which likely underlies the overactive tissue mineralization seen in patients. Decreased type I collagen expression, secretion, and matrix incorporation establish type V OI as a collagen-related defect.
C1 [Reich, Adi; Bae, Alison S.; Barnes, Aileen M.; Cabral, Wayne A.; Marini, Joan C.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bone & Extracellular Matrix Branch, Bethesda, MD 20892 USA.
[Hill, Suvimol C.] NIH, Dept Diagnost Radiol, Ctr Clin, Bethesda, MD 20892 USA.
[Hinek, Aleksander] Univ Toronto, Hosp Sick Children, Ctr Heart, Expt Med Program, Toronto, ON M5S 3OA4, Canada.
[Stimec, Jennifer] Univ Toronto, Hosp Sick Children, Dept Pediat, Div Diagnost Imaging, Toronto, ON M5G 1X8, Canada.
[Chitayat, David] Univ Toronto, Hosp Sick Children, Dept Pediat, Div Clin & Metab Genet, Toronto, ON M5G 1X8, Canada.
[Chitayat, David] Univ Toronto, Mt Sinai Hosp, Dept Obstet & Gynecol, Prenatal Diag & Med Genet Program, Toronto, ON M5G 1Z5, Canada.
RP Marini, JC (reprint author), Bone & Extracellular Matrix Branch, Bldg 10,Room 10D39,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM oidoc@helix.nih.gov
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development
FX This work was supported by Eunice Kennedy Shriver National Institute of
Child Health and Human Development intramural funding (to J.C.M.).
NR 35
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U1 0
U2 2
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0021-972X
EI 1945-7197
J9 J CLIN ENDOCR METAB
JI J. Clin. Endocrinol. Metab.
PD FEB
PY 2015
VL 100
IS 2
BP E325
EP E332
DI 10.1210/jc.2014-3082
PG 8
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA CG5RF
UT WOS:000353350900026
PM 25387264
ER
PT J
AU Sklavos, MM
Stratton, P
Giri, N
Alter, BP
Savage, SA
Pinto, LA
AF Sklavos, Martha M.
Stratton, Pamela
Giri, Neelam
Alter, Blanche P.
Savage, Sharon A.
Pinto, Ligia A.
TI Reduced Serum Levels of Anti-Mullerian Hormone in Females With Inherited
Bone Marrow Failure Syndromes
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID DIAMOND-BLACKFAN ANEMIA; PRIMARY OVARIAN INSUFFICIENCY; ANTIMULLERIAN
HORMONE; DYSKERATOSIS-CONGENITA; MENSTRUAL-CYCLE; FANCONI-ANEMIA;
RESERVE; TRANSPLANTATION; CANCER; CHEMOTHERAPY
AB Context: Previously, reduced levels of anti-Mullerian hormone (AMH), a circulating marker of ovarian reserve, were found in females with Fanconi anemia (FA). FA, dyskeratosis congenita (DC), and Diamond-Blackfan anemia (DBA) are inherited bone marrow failure syndromes (IBMFS) associated with high risks of bone marrow failure, leukemia, and solid tumors.
Objective: The objective of the study was to assess AMH levels in females with DC or DBA.
Design and Setting: This observational study used the National Cancer Institute's inherited bone marrow failure syndrome cohort at the National Institutes of Health Clinical Center.
Participants: The study included females with DC, unaffected female relatives of patients with DC, females with DBA, unaffected female relatives of patients with DBA, and unrelated healthy female volunteers younger than 41 years of age.
Main Outcome measure: Serum AMH levels were measured.
Results: Females with DC had significantly lower levels of AMH(median 0.55 ng/mL) compared with unaffected relatives (median 2.28 ng/mL, P = .004) or unrelated healthy volunteers (median 2.69 ng/mL, P = .005). Females with DBA showed a nonsignificant trend for lower levels of AMH(median 0.89 ng/mL) compared with unaffected relatives (median 1.71 ng/mL, P = .21) or unrelated healthy volunteers (P = .11). Patients with DC and DBA had significantly higher levels of AMH (P = .013, P = .003) compared with FA (median 0.05 ng/mL).
Conclusions: Our findings suggest that women with IBMFS have lower levels of AMH than unaffected women. This AMH deficiency could be a primary ovarian defect or a consequence of the pathophysiology of the syndromes. Additional studies of AMH and ovarian function in women with IBMFS are warranted to better understand the underlying biology.
C1 [Sklavos, Martha M.; Pinto, Ligia A.] Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Human Papillomavirus Immunol Lab, Frederick, MD 21702 USA.
[Stratton, Pamela] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD 20892 USA.
[Giri, Neelam; Alter, Blanche P.; Savage, Sharon A.] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20852 USA.
RP Pinto, LA (reprint author), Leidos Biomed Res Inc, Human Papillomavirus Immunol Lab, Bldg 469,Room 111,1050 Boyles St, Frederick, MD 21702 USA.
EM pintol@mail.nih.gov
RI Savage, Sharon/B-9747-2015
OI Savage, Sharon/0000-0001-6006-0740
FU Fanconi Anemia Research Fund; Intramural Research Program of the
Division of Cancer Epidemiology and Genetics, National Cancer Institute
of the National Institutes of Health; National Institutes of Health
Clinical Center; Intramural Program of the Eunice Kennedy Shriver
National Institute of Child Health and Human Development; Westat, Inc.
[N02-CP-91026, N02-CP-11019, HHSN261200655001C]; National Cancer
Institute of the National Institutes of Health [HHSN261200800001E]
FX This work was supported in part by the Fanconi Anemia Research Fund
(fanconi.org) (to N.G.); in part by the Intramural Research Program of
the Division of Cancer Epidemiology and Genetics, National Cancer
Institute of the National Institutes of Health (to B.P.A. and N.G.), the
National Institutes of Health Clinical Center, and the Intramural
Program of the Eunice Kennedy Shriver National Institute of Child Health
and Human Development. The study was also supported by Contracts
N02-CP-91026, N02-CP-11019, and HHSN261200655001C from Westat, Inc. This
project also has been funded in whole or in part with federal funds from
the National Cancer Institute of the National Institutes of Health under
Contract HHSN261200800001E.
NR 36
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Z9 1
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0021-972X
EI 1945-7197
J9 J CLIN ENDOCR METAB
JI J. Clin. Endocrinol. Metab.
PD FEB
PY 2015
VL 100
IS 2
BP E197
EP E203
DI 10.1210/jc.2014-2838
PG 7
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA CG5RF
UT WOS:000353350900009
PM 25405500
ER
PT J
AU Marx, SJ
AF Marx, Stephen J.
TI Letter to the Editor: Distinguishing Typical Primary Hyperparathyroidism
From Familial Hypocalciuric Hypercalcemia by Using an Index of Urinary
Calcium
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Letter
ID 4TH INTERNATIONAL WORKSHOP
C1 NIDDK, Genet & Endocrinol Sect, NIH, Bethesda, MD 20892 USA.
RP Marx, SJ (reprint author), NIDDK, Genet & Endocrinol Sect, NIH, Bethesda, MD 20892 USA.
EM marxs@mail.nih.gov
FU Intramural NIH HHS
NR 9
TC 2
Z9 2
U1 0
U2 1
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0021-972X
EI 1945-7197
J9 J CLIN ENDOCR METAB
JI J. Clin. Endocrinol. Metab.
PD FEB
PY 2015
VL 100
IS 2
BP L29
EP U90
DI 10.1210/jc.2014-4221
PG 3
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA CG5RF
UT WOS:000353350900008
PM 25658165
ER
PT J
AU Modali, SD
Parekh, VI
Kebebew, E
Agarwal, SK
AF Modali, Sita D.
Parekh, Vaishali I.
Kebebew, Electron
Agarwal, Sunita K.
TI Epigenetic Regulation of the lncRNA MEG3 and Its Target c-MET in
Pancreatic Neuroendocrine Tumors
SO MOLECULAR ENDOCRINOLOGY
LA English
DT Article
ID ENDOCRINE NEOPLASIA TYPE-1; DIFFERENTIALLY METHYLATED REGION;
TRANSCRIPTION REPRESSOR DAXX; LONG NONCODING RNAS; INSULIN-SECRETION;
MEN1 GENE; CELL-PROLIFERATION; PITUITARY-TUMORS; DNA METHYLATION;
PROMOTER REGION
AB Biallelic inactivation of MEN1 encoding menin in pancreatic neuroendocrine tumors (PNETs) associated with the multiple endocrine neoplasia type 1 (MEN1) syndrome is well established, but how menin loss/inactivation initiates tumorigenesis is not well understood. We show that menin activates the long noncoding RNA maternally expressed gene 3 (Meg3) by histone-H3 lysine-4 trimethylation and CpG hypomethylation at the Meg3 promoter CRE site, to allow binding of the transcription factor cAMP response element-binding protein. We found that Meg3 has tumorsuppressor activity in PNET cells because the overexpression of Meg3 in MIN6 cells (insulin-secreting mouse PNET cell line) blocked cell proliferation and delayed cell cycle progression. Gene expression microarray analysis showed that Meg3 overexpression in MIN6 mouse insulinoma cells down-regulated the expression of the protooncogene c-Met (hepatocyte growth factor receptor), and these cells showed significantly reduced cell migration/invasion. Compared with normal islets, mouse or human MEN1-associated PNETs expressed less MEG3 and more c-MET. Therefore, a tumor-suppressor long noncoding RNA (MEG3) and suppressed protooncogene (c-MET) combination could elicit menin's tumor-suppressor activity. Interestingly, MEG3 and c-MET expression was also altered in human sporadic insulinomas (insulin secreting PNETs) with hypermethylation at the MEG3 promoter CRE-site coinciding with reduced MEG3 expression. These data provide insights into the beta-cell proliferation mechanisms that could retain their functional status. Furthermore, in MIN6 mouse insulinoma cells, DNA-demethylating drugs blocked cell proliferation and activated Meg3 expression. Our data suggest that the epigenetic activation of lncRNA MEG3 and/or inactivation of c-MET could be therapeutic for treating PNETs and insulinomas.
C1 [Modali, Sita D.; Parekh, Vaishali I.; Agarwal, Sunita K.] NCI, Metab Dis Branch, NIH, Bethesda, MD 20892 USA.
[Kebebew, Electron] NCI, NIDDK, NIH, Bethesda, MD 20892 USA.
[Kebebew, Electron] NCI, Endocrine Oncol Branch, NIH, Bethesda, MD 20892 USA.
RP Agarwal, SK (reprint author), NIH, Bldg 10,Room 8C-101, Bethesda, MD 20892 USA.
EM sunitaa@mail.nih.gov
RI Agarwal, Sunita/D-1428-2016
OI Agarwal, Sunita/0000-0002-7557-3191
FU Intramural Program of the National Institute of Diabetes and Digestive
and Kidney Diseases [1ZIADK07503503]; National Cancer Institute
[1ZIABC01127503]
FX This work was supported by the Intramural Program of the National
Institute of Diabetes and Digestive and Kidney Diseases (Project
1ZIADK07503503, to SK.A.) and the National Cancer Institute (Project
1ZIABC01127503, to E.K.).
NR 47
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U1 3
U2 5
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0888-8809
J9 MOL ENDOCRINOL
JI Mol. Endocrinol.
PD FEB
PY 2015
VL 29
IS 2
BP 224
EP 237
DI 10.1210/me.2014-1304
PG 14
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA CG4XD
UT WOS:000353291200007
PM 25565142
ER
PT J
AU Moody, TW
Mantey, SA
Moreno, P
Nakamura, T
Lacivita, E
Leopoldo, M
Jensen, RT
AF Moody, Terry W.
Mantey, Samuel A.
Moreno, Paola
Nakamura, Taichi
Lacivita, Enza
Leopoldo, Marcello
Jensen, Robert T.
TI ML-18 is a non-peptide bombesin receptor subtype-3 antagonist which
inhibits lung cancer growth
SO PEPTIDES
LA English
DT Article
DE Bombesin receptor subtype 3; Nonpeptide antagonist; Lung cancer;
Proliferation
ID GASTRIN-RELEASING-PEPTIDE; HUMAN ORPHAN RECEPTOR; HIGH-AFFINITY;
TYROSINE PHOSPHORYLATION; CARCINOMA CELLS; EXPRESSION; AGONISTS;
PHARMACOLOGY; CLONING; IDENTIFICATION
AB Bombesin receptor subtype (BRS)-3 is a G protein coupled receptor (GPCR) for the bombesin (BB)-family of peptides. BRS-3 is an orphan GPCR and little is known of its physiological role due to the lack of specific agonists and antagonists. PD168368 is a nonpeptide antagonist for the neuromedin B (NMB) receptor (R) whereas PD176252 is a nonpeptide antagonist for the gastrin releasing peptide (GRP) R and NMBR but not BRS-3. Here nonpeptide analogs of PD176252 e.g. the S-enantiomer ML-18, and the R-enantiomer, EMY-98, were investigated as BRS-3 antagonists using lung cancer cells. ML-18 and EMY-98 inhibited specific I-125-BA1 (DTyr-Gln-Trp-Ala-Val-beta Ala-His-Phe-Nle-NH2)BB6-14 binding to NCI-H1299 lung cancer cells stably transfected with BRS-3 with IC50 values of 4.8 and >100 mu M, respectively. In contrast, ML-18 bound with lower affinity to the GRPR and NMBR with IC50 values of 16 and >100 mu M, respectively. ML-18 (16 mu M), but not its enantiomer EMY-98, inhibited the ability of 10 nM BA1 to elevate cytosolic Ca2+ in a reversible manner using lung cancer cells loaded with FURA2-AM. ML-18 (16 mu M), but not EMY-98, inhibited the ability of 100 nM BA1 to cause tyrosine phosphorylation of the EGFR and ERK in lung cancer cells. ML-18 but not EMY-98 inhibited the proliferation of lung cancer cells. The results indicate that ML-18 is a nonpeptide BRS-3 antagonist that should serve as a template to improve potency and selectivity. Published by Elsevier Inc.
C1 [Moody, Terry W.] NCI, Dept Hlth & Human Serv, Ctr Canc Res, Off Director, Bethesda, MD 20892 USA.
[Mantey, Samuel A.; Moreno, Paola; Nakamura, Taichi; Jensen, Robert T.] Natl Inst Diabet Digest & Kidney Dis, Digest Dis Branch, Bethesda, MD 20892 USA.
[Lacivita, Enza; Leopoldo, Marcello] Univ Bari A Moro, Dipartimento Farm, Sci Farmaco, Bari, Italy.
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
OI Leopoldo, Marcello/0000-0001-8401-2815; Lacivita,
Enza/0000-0003-2443-1174
FU intramural program of NCI; intramural program of NIDDK of the NIH
FX The authors thank Dr. D. Coy (Tulane Univ.) for the BA1 and Drs. M.
Nicklaus and M. Peach NCI for helpful discussions. This research is
supported by the intramural programs of NCI and NIDDK of the NIH.
NR 41
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U1 2
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0196-9781
EI 1873-5169
J9 PEPTIDES
JI Peptides
PD FEB
PY 2015
VL 64
BP 55
EP 61
DI 10.1016/j.peptides.2014.12.005
PG 7
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism;
Pharmacology & Pharmacy
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism;
Pharmacology & Pharmacy
GA CF8KM
UT WOS:000352808100009
PM 25554218
ER
PT J
AU Heissler, SM
Sellers, JR
AF Heissler, Sarah M.
Sellers, James R.
TI Four Things to Know about Myosin Light Chains as Reporters for
Non-muscle Myosin-2 Dynamics in Live Cells
SO CYTOSKELETON
LA English
DT Editorial Material
DE regulatory light chain; myosin; GFP; cell motility; phosphomimetics
ID MOLECULAR MOTOR; MIGRATING CELLS; POINT MUTATION; IN-VIVO; II-C;
PHOSPHORYLATION; PROTEIN; CYTOKINESIS; BINDING; TRAFFICKING
AB The interplay between non-muscle myosins-2 and filamentous actin results in cytoplasmic contractility which is essential for eukaryotic life. Concomitantly, there is tremendous interest in elucidating the physiological function and temporal localization of non-muscle myosin-2 in cells. A commonly used method to study the function and localization of non-muscle myosin-2 is to overexpress a fluorescent protein (FP)-tagged version of the regulatory light chain (RLC) which binds to the myosin-2 heavy chain by mass action. Caveats about this approach include findings from recent studies indicating that the RLC does not bind exclusively to the non-muscle myosin-2 heavy chain. Rather, it can also associate with the myosin heavy chains of several other classes as well as other targets than myosin. In addition, the presence of the FP moiety may compromise myosin's enzymatic and mechanical performance. This and other factors to be discussed in this commentary raise questions about the possible complications in using FP-RLC as a marker for the dynamic localization and regulatory aspects of non-muscle myosin-2 motor functions in cell biological experiments. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.
C1 [Heissler, Sarah M.; Sellers, James R.] NHLBI, Lab Mol Physiol, NIH, Bethesda, MD 20892 USA.
RP Sellers, JR (reprint author), NHLBI, Lab Mol Physiol, NIH, Bethesda, MD 20892 USA.
EM sellersj@nhlbi.nih.gov
FU Intramural NIH HHS [Z01 HL001786-29]; NHLBI NIH HHS [Z01 HL001786]
NR 48
TC 3
Z9 3
U1 2
U2 6
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 FEB
PY 2015
VL 72
IS 2
BP 65
EP 70
DI 10.1002/cm.21212
PG 6
WC Cell Biology
SC Cell Biology
GA CG1PW
UT WOS:000353046500001
PM 25712372
ER
PT J
AU Pollack, AZ
Louis, GMB
Chen, Z
Sun, L
Trabert, B
Guo, Y
Kannan, K
AF Pollack, A. Z.
Louis, G. M. Buck
Chen, Z.
Sun, L.
Trabert, B.
Guo, Y.
Kannan, K.
TI Bisphenol A, benzophenone-type ultraviolet filters, and phthalates in
relation to uterine leiomyoma
SO ENVIRONMENTAL RESEARCH
LA English
DT Article
DE Benzophenone; Bisphenol A; Fibroid; Phthalate; Ultraviolet filter
ID HIGH PLASMA-CONCENTRATIONS; TANDEM MASS-SPECTROMETRY; PERSONAL CARE
PRODUCTS; HUMAN EXPOSURE; ESTROGENIC ACTIVITY; FEMALE RATS; UV-FILTERS;
IN-VITRO; DI-(2-ETHYLHEXYL) PHTHALATE; POLYCHLORINATED-BIPHENYLS
AB Bisphenol A, benzophenone-type UV filters, and phthalates are chemicals in high production and use including in a range of personal care products. Exposure of humans to these chemicals has been shown to affect endocrine function. Although short-lived, widespread exposure may lead to continual opportunity for these chemicals to elicit health effects in humans. The association of these chemicals with incident uterine leiomyoma, an estrogen sensitive disease, is not known. Urinary concentrations of bisphenol A (BPA), five benzophenone-type UV filters (2-hydroxy-4-methoxybenzophenone (2OH-4MeO-BP), 2,4-dihydroxybenzophenone (2,4'OH-BP), 2,2'-dihydroxybenzophenone (2,2'OH-4MeO-BP), 2,2'4,4'-tetrahydroxybenzophenone (2,2'4,4'OH-BP), and 4-hydroxybenzophenone (4OH-BP), and 14 phthalate monoesters were quantified in 495 women who later underwent laparoscopy/laparotomy at 14 clinical sites for the diagnosis of fibroids. Significantly higher geometric mean creatinine-corrected concentrations of BPA, 2,4OH-BP, and 2OH-4MeO-BP were observed in women with than without fibroids [BPA: 2.09 mu g/g vs. 1.46 mu g/g p=0.004; 2,4OH-BP:11.10 mu g/g vs. 6.71 mu g/g p=0.01; 2OH-4MeO-BP: 11.31 mu g/g vs. 6.10 mu g/p=0.01]. Mono-methyl phthalate levels were significantly lower in women with than without fibroids (1.78 mu g/g vs. 2.40 mu g/g). However, none of the exposures were associated with a significant odds ratio even when adjusting for relevant covariates. There was a lack of an association between select nonpersistent chemicals and the odds of a fibroid diagnosis. (C) 2014 Elsevier Inc. All rights reserved.
C1 [Pollack, A. Z.; Louis, G. M. Buck; Chen, Z.; Sun, L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, NIH, Rockville, MD 20852 USA.
[Trabert, B.] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Guo, Y.; Kannan, K.] SUNY Albany, Div Environm Hlth Sci, Wadsworth Ctr, New York State Dept Hlth, Albany, NY 12201 USA.
[Guo, Y.; Kannan, K.] SUNY Albany, Dept Environm Hlth Sci, Albany, NY 12201 USA.
RP Pollack, AZ (reprint author), George Mason Univ, Coll Hlth & Human Serv, Global & Community Hlth, 4400 Univ Dr MS5B7, Fairfax, VA 22030 USA.
EM apollac2@gmu.edu; louisg@mail.nih.gov; chenzhe@mail.nih.gov;
sunl3@mail.nih.gov; britton.trabert@nih.gov;
yxg03@notes.health.state.ny.us; kkannan@wadsworth.edu
RI Trabert, Britton/F-8051-2015;
OI Pollack, Anna/0000-0002-4313-3298; Buck Louis,
Germaine/0000-0002-1774-4490
FU Intramural Research Program; Eunice Kennedy Shriver National Institute
of Child Health and Human Development, National Institutes of Health
[NO1-DK-6-3428, NO1-DK-6-3427, 10001406-02]
FX This study was funded by the Intramural Research Program, Eunice Kennedy
Shriver National Institute of Child Health and Human Development,
National Institutes of Health (contracts NO1-DK-6-3428, NO1-DK-6-3427,
and 10001406-02).
NR 78
TC 11
Z9 11
U1 5
U2 22
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0013-9351
EI 1096-0953
J9 ENVIRON RES
JI Environ. Res.
PD FEB
PY 2015
VL 137
BP 101
EP 107
DI 10.1016/j.envres.2014.06.028
PG 7
WC Environmental Sciences; Public, Environmental & Occupational Health
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health
GA CF1TO
UT WOS:000352331000013
PM 25531814
ER
PT J
AU Espejo-Herrera, N
Cantor, KP
Malats, N
Silverman, DT
Tardon, A
Garcia-Closas, R
Serra, C
Kogevinas, M
Villanueva, CM
AF Espejo-Herrera, Nadia
Cantor, Kenneth P.
Malats, Nuria
Silverman, Debra T.
Tardon, Adonina
Garcia-Closas, Reina
Serra, Consol
Kogevinas, Manolis
Villanueva, Cristina M.
TI Nitrate in drinking water and bladder cancer risk in Spain
SO ENVIRONMENTAL RESEARCH
LA English
DT Article
DE Nitrate; Drinking water; Water contaminants; Bladder cancer;
Case-control study
ID N-NITROSO COMPOUNDS; GASTROINTESTINAL-TRACT; ENDOGENOUS FORMATION;
NETHERLANDS COHORT; ADULT GLIOMA; LOS-ANGELES; RED MEAT; HEALTH;
MUNICIPAL; HEME
AB Background: Nitrate is a widespread contaminant in drinking water and ingested nitrate under conditions resulting in endogenous nitrosation is suspected to be carcinogenic. However, the suggested association between nitrate in drinking water and bladder cancer remains inconsistent. We evaluated the long-term exposure to drinking water nitrate as a risk factor for bladder cancer, considering endogenous nitrosation modifiers and other covariables.
Methods: We conducted a hospital-based case-control study of bladder cancer in Spain (1998-2001). Residential histories and water consumption information were ascertained through personal interviews. Historical nitrate levels (1940-2000) were estimated in study municipalities based on monitoring records and water source. Residential histories of study subjects were linked with nitrate estimates by year and municipality to calculate individual exposure from age 18 to recruitment. We calculated odds ratios (OR) and 95% confidence intervals (CI) for bladder cancer among 531 cases and 556 controls with reliable interviews and nitrate exposure information covering at least 70% of years from age 18 to interview.
Results: Average residential levels ranged from 2.1 mg/L to 12.0 mg/L among regions. Adjusted OR (95% CI) for average residential levels relative to <= 5 mg/L were 1.2 (0.7-2.0) for > 5-10 mg/L and 1.1 (0.6-1.9) for > 10 mg/L. The OR for subjects with longest exposure duration (> 20 years) to highest levels (> 9.5 mg/L) was 1.4 (0.9-2.3). Stratification by intake of vitamin C, vitamin E, meat, and gastric ulcer diagnosis did not modify these results. A non-significant negative association was found with waterborne ingested nitrate with an OR of 0.7 (0.4-1.0) for > 8 vs. <= 4 mg/day. Adjustment for several covariables showed similar results to crude analyses.
Conclusion: Bladder cancer risk was inconsistently associated with chronic exposure to drinking water nitrate at levels below the current regulatory limit. Elevated risk is suggested only among subjects with longest exposure duration to the highest levels. No evidence of interaction with endogenous nitrosation modifiers was observed. (C) 2014 Elsevier Inc. All rights reserved.
C1 [Espejo-Herrera, Nadia; Kogevinas, Manolis; Villanueva, Cristina M.] Ctr Recerca Epidemiol Ambiental CREAL, Barcelona 08003, Spain.
[Espejo-Herrera, Nadia; Serra, Consol; Kogevinas, Manolis; Villanueva, Cristina M.] Univ Pompeu Fabra, Dept Ciencies Expt & Salut, Barcelona, Spain.
[Espejo-Herrera, Nadia; Kogevinas, Manolis; Villanueva, Cristina M.] CIBER Epidemiol & Salud Publ CIBERESP, Barcelona, Spain.
[Cantor, Kenneth P.; Silverman, Debra T.] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Malats, Nuria] Spanish Natl Canc Res Ctr CNIO, Genet & Mol Epidemiol Grp, Madrid, Spain.
[Tardon, Adonina] Univ Oviedo, Oviedo, Spain.
[Garcia-Closas, Reina] Hosp Univ Canarias, San Cristobal la Laguna, Spain.
[Serra, Consol] Consorci Hosp Parc Tauli, Sabadell, Spain.
[Kogevinas, Manolis; Villanueva, Cristina M.] Hosp del Mar, Med Res Inst, IMIM, Barcelona, Spain.
[Kogevinas, Manolis] Natl Sch Publ Hlth, Athens, Greece.
RP Villanueva, CM (reprint author), Ctr Recerca Epidemiol Ambiental CREAL, Doctor Aiguader 88, Barcelona 08003, Spain.
EM cvillanueva@creal.cat
RI Malats, Nuria/H-7041-2015; Villanueva, Cristina/N-1942-2014; Kogevinas,
Manolis/C-3918-2017
OI Malats, Nuria/0000-0003-2538-3784; Villanueva,
Cristina/0000-0002-0783-1259;
FU Intramural Research Program of the National Institute of Health,
National Cancer Institute, United States, Division of Cancer
Epidemiology and Genetics [NCI NO2-CP-11015]; Spanish Health Ministry
[FIS/Spain 00/0745, ISIII-G03/174, FIS PI11/00226]; European Union
[BMH4-98-3243]; Agencia de Gestio d'Ajuts Universitaris i de Recerca
(AGAUR FI-DGR) Generalitat de Cataluna, Spain
FX This study was supported by the Intramural Research Program of the
National Institute of Health, National Cancer Institute, United States,
Division of Cancer Epidemiology and Genetics (Contract NCI
NO2-CP-11015). The project also received funding from the Spanish Health
Ministry (FIS/Spain 00/0745, ISIII-G03/174, FIS PI11/00226), and the
European Union (BMH4-98-3243). N. Espejo-Herrera receives financial
support for the Ph.D. program from the Agencia de Gestio d'Ajuts
Universitaris i de Recerca (AGAUR FI-DGR 2013) Generalitat de Cataluna,
Spain.
NR 41
TC 6
Z9 6
U1 0
U2 19
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0013-9351
EI 1096-0953
J9 ENVIRON RES
JI Environ. Res.
PD FEB
PY 2015
VL 137
BP 299
EP 307
DI 10.1016/j.envres.2014.10.034
PG 9
WC Environmental Sciences; Public, Environmental & Occupational Health
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health
GA CF1TO
UT WOS:000352331000036
PM 25601732
ER
PT J
AU Robledo, CA
Mendola, P
Yeung, E
Mannisto, T
Sundaram, R
Liu, DP
Ying, Q
Sherman, S
Grantz, KL
AF Robledo, Candace A.
Mendola, Pauline
Yeung, Edwina
Maennistoe, Tuija
Sundaram, Rajeshwari
Liu, Danping
Ying, Qi
Sherman, Seth
Grantz, Katherine L.
TI Preconception and early pregnancy air pollution exposures and risk of
gestational diabetes mellitus
SO ENVIRONMENTAL RESEARCH
LA English
DT Article
DE Preconception; Pregnancy; Air pollution; Gestational diabetes
ID LONG-TERM EXPOSURE; C-REACTIVE PROTEIN; INSULIN-RESISTANCE; PARTICULATE
MATTER; LOS-ANGELES; INFLAMMATION; ASSOCIATION; COHORT; WOMEN; MODEL
AB Background: Air pollution has been linked to gestational diabetes mellitus (GDM) but no studies have evaluated impact of preconception and early pregnancy air pollution exposures on GDM risk.
Methods: Electronic medical records provided data on 219,952 singleton deliveries to mothers with (n=11,334) and without GDM (n=208,618). Average maternal exposures to particulate matter (PM) <= 2.5 mu m (PM2.5) and PM2.5 constituents, PM <= 10 mu m (PM10), nitrogen oxides (NOx), carbon monoxide, sulfur dioxide (SO2) and ozone (O-3) were estimated for the 3-month preconception window, first trimester, and gestational weeks 1-24 based on modified Community Multiscale Air Quality models for delivery hospital referral regions. Binary regression models with robust standard errors estimated relative risks (RR) for GDM per interquartile range (IQR) increase in pollutant concentrations adjusted for study site, maternal age and race/ethnicity.
Results: Preconception maternal exposure to NOX (RR=1.09, 95% CI: 1.04, 1.13) and SO2 (RR=1.05, 1.01, 1.09) were associated with increased risk of subsequent GDM and risk estimates remained elevated for first trimester exposure. Preconception O-3 was associated with lower risk of subsequent GDM (RR=0.93, 0.90, 0.96) but risks increased later in pregnancy.
Conclusion: Maternal exposures to NOx and SO2 preconception and during the first few weeks of pregnancy were associated with increased GDM risk. O-3 appeared to increase GDM risk in association with mid-pregnancy exposure but not in earlier time windows. These common exposures merit further investigation. Published by Elsevier Inc.
C1 [Robledo, Candace A.; Mendola, Pauline; Yeung, Edwina; Maennistoe, Tuija; Grantz, Katherine L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Div Intramural Populat Hlth Res, Epidemiol Branch, Rockville, MD 20852 USA.
[Sundaram, Rajeshwari; Liu, Danping] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Div Intramural Populat Hlth Res, Biostat & Bioinformat Branch, Rockville, MD 20852 USA.
[Ying, Qi] Texas A&M Univ, Zachary Dept Civil Engn, College Stn, TX 77845 USA.
[Sherman, Seth] EMMES Corp, Rockville, MD 20852 USA.
RP Mendola, P (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Intramural Populat Hlth Res, NIH, 6100 Execut Blvd,Room 7B13E, Rockville, MD 20852 USA.
EM pauline.mendola@mail.nih.gov
RI Yeung, Edwina/F-5992-2015;
OI Yeung, Edwina/0000-0002-3851-2613; Sherman, Seth/0000-0003-3667-9898;
Mannisto, Tuija/0000-0002-6382-9153; Mendola,
Pauline/0000-0001-5330-2844; Sundaram, Rajeshwari/0000-0002-6918-5002;
Grantz, Katherine/0000-0003-0276-8534
FU Eunice Kennedy Shriver National Institute of Child Health & Human
Development, National Institutes of Health [HHSN257200603425C,
HHSN275200800002I, HHSN27500008]
FX This work was supported by the Intramural Research Program of the Eunice
Kennedy Shriver National Institute of Child Health & Human Development,
National Institutes of Health through Contract no. HHSN257200603425C for
the Consortium on Safe Labor, and through Contract no.
HHSN275200800002I, Task no. HHSN27500008 for the Air Quality and
Reproductive Health Study.
NR 39
TC 14
Z9 15
U1 4
U2 16
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0013-9351
EI 1096-0953
J9 ENVIRON RES
JI Environ. Res.
PD FEB
PY 2015
VL 137
BP 316
EP 322
DI 10.1016/j.envres.2014.12.020
PG 7
WC Environmental Sciences; Public, Environmental & Occupational Health
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health
GA CF1TO
UT WOS:000352331000038
PM 25601734
ER
PT J
AU Bae, J
Kim, S
Kannan, K
Louis, GMB
AF Bae, Jisuk
Kim, Sungduk
Kannan, Kurunthachalam
Louis, Germaine M. Buck
TI Couples' urinary bisphenol A and phthalate metabolite concentrations and
the secondary sex ratio
SO ENVIRONMENTAL RESEARCH
LA English
DT Article
DE Bisphenol A; Endocrine disruptors; Fertility; Phthalates; Sex ratio
ID ENDOCRINE-DISRUPTING CHEMICALS; BUTYL BENZYL PHTHALATE; HUMAN EXPOSURE;
REPRODUCTIVE FUNCTION; DEVELOPMENTAL TOXICITY; PERINATAL EXPOSURE;
DIETARY EXPOSURE; UNITED-STATES; SEMEN QUALITY; NTP CENTER
AB With limited research focusing on non-persistent chemicals as exogenous factors affecting human sex selection, this study aimed to evaluate the association of urinary bisphenol A (BPA) and phthalate metabolite concentrations with the secondary sex ratio (SSR), defined as the ratio of male to female live births. The current analysis is limited to singleton live births (n=220, 43.9%) from the Longitudinal Investigation of Fertility and the Environment (LIFE) Study, in which couples discontinuing contraception with the intention of becoming pregnant were enrolled and followed while trying for pregnancy and through delivery for those achieving pregnancy. Using modified Poisson regression models accounting for potential confounders, we estimated the relative risks (RRs) of a male birth per standard deviation change in the log-transformed maternal, paternal, and couple urinary BPA and 14 phthalate metabolite concentrations (ng/mL) measured upon enrollment When maternal and paternal chemical concentrations were modeled jointly, paternal BPA (RR, 0.77; 95% confidence interval [CI], 0.62-0.95) and mono-isobutyl phthalate (RR, 0.82; 95% Cl, 0.67-1.00) were significantly associated with a female excess. Contrarily, maternal BPA (RR, 1.16; 95% Cl, 1.03-131), mono-isobutyl phthalate (RR, 1.28; 95% CI, 1.06-1.54), mono-benzyl phthalate (RR, 131; 95% Cl, 1.08-1.58), and mono-n-butyl phthalate (RR, 124; 95% CI, 1.01-1.51) were significantly associated with a male excess. These findings underscore varying patterns for the SSR in relation to parental exposures. Given the absence of previous investigation, these partner-specific associations of non-persistent chemicals with the SSR need future corroboration. (C) 2014 Elsevier Inc. All rights reserved.
C1 [Bae, Jisuk; Kim, Sungduk; Louis, Germaine M. Buck] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, NIH, Rockville, MD 20852 USA.
[Bae, Jisuk] Catholic Univ, Sch Med, Dept Prevent Med, Daegu 705718, South Korea.
[Kannan, Kurunthachalam] SUNY Albany, Sch Publ Hlth, Wadsworth Ctr, New York State Dept Hlth, Albany, NY 12201 USA.
[Kannan, Kurunthachalam] SUNY Albany, Sch Publ Hlth, Dept Environm Hlth Sci, Albany, NY 12201 USA.
RP Bae, J (reprint author), Catholic Univ, Sch Med, Dept Prevent Med, 33 Duryugongwon Ro 17 Gil, Daegu 705718, South Korea.
EM jisuk.bae@nih.gov; kims2@mail.nih.gov; kkannan@wadsworth.org;
louisg@mail.nih.gov
OI Buck Louis, Germaine/0000-0002-1774-4490
FU Kennedy Shriver National Institute of Child Health and Human Development
National Institutes of Health [N01-HD-3-3355, N01-HD-3-3356,
N01-HD-3-3358]; Korea-US Visiting Scientist Training Award (VSTA) of the
Eunice Kennedy Shriver National Institute of Child Health and Human
Development National Institutes of Health [VFTB057303]
FX This study was supported by the Intramural Research Program of the
Eunice Kennedy Shriver National Institute of Child Health and Human
Development National Institutes of Health (contracts #N01-HD-3-3355,
N01-HD-3-3356, N01-HD-3-3358). Dr. Bae was supported by the Korea-US
Visiting Scientist Training Award (VSTA) of the Eunice Kennedy Shriver
National Institute of Child Health and Human Development National
Institutes of Health (award #VFTB057303).
NR 77
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U1 0
U2 14
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0013-9351
EI 1096-0953
J9 ENVIRON RES
JI Environ. Res.
PD FEB
PY 2015
VL 137
BP 450
EP 457
DI 10.1016/j.envres.2014.11.011
PG 8
WC Environmental Sciences; Public, Environmental & Occupational Health
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health
GA CF1TO
UT WOS:000352331000054
PM 25677702
ER
PT J
AU Kemp, TJ
Matsui, K
Shelton, G
Safaeian, M
Pinto, LA
AF Kemp, Troy J.
Matsui, Ken
Shelton, Gloriana
Safaeian, Mahboobeh
Pinto, Ligia A.
TI A comparative study of two different assay kits for the detection of
secreted alkaline phosphatase in HPV antibody neutralization assays
SO HUMAN VACCINES & IMMUNOTHERAPEUTICS
LA English
DT Article
DE Cervarix (R); Gardasil (R); human papillomavirus; SEAP; vaccine; ZiVa
ID HUMAN-PAPILLOMAVIRUS TYPE-16; RICA VACCINE TRIAL; IN-VITRO;
CERVICAL-CANCER; PSEUDOVIRIONS; RESPONSES; L2; GENERATION; INFECTION;
INHIBITION
AB To assess immunogenicity and development of antibodies in the context of vaccination, it is critical to quantify titers of neutralizing antibodies. We have been employing the 293TT cell-based neutralization assay system to quantify anti-HPV neutralizing antibodies. In this system, human papillomavirus (HPV) pseudovirion (PsV) particles encapsidating secreted alkaline phosphatase (SEAP) gene are used to measure infection of 293TT cells in 72-hr cell-culture supernatants. SEAP has traditionally been measured by Great EscAPe (TM) SEAP Chemiluminescence Kit 2.0 (GE). To reduce the cost, and to potentially increase efficiency, we sought a cheaper kit with better detection capability. Performance characteristics of the newer chemiluminescence kit, ZiVa (R) Ultra SEAP Plus Assay (Ziva) and GE were compared using the 293TT system. Dose titration of HPV PsV 16 or 18 showed that signal-to-noise ratios at 48 and 72 hr post-infection were higher for ZiVa at nearly all doses. ZiVa was superior to GE as it was able to detect SEAP at 48 hr, as well as when lower numbers of 293TT cells were used. The ability of ZiVa to quantitate HPV-16 and -18 neutralizing antibody titers was tested using sera from Cervarix (R) immunized individuals. Spearman rank correlational analyses showed excellent correlations between the titers obtained with ZiVa and GE for anti-HPV16 (r = 0.9822, p < 0.0001) and anti-HPV18 (r = 0.9832, p < 0.0001) antibodies. We concluded that ZiVa is superior to GE in detecting SEAP, and the antibody titers in sera of vaccinated individuals were similar to those obtained with GE. Thus, Ziva is a suitable alternative to GE.
C1 [Kemp, Troy J.; Matsui, Ken; Shelton, Gloriana; Pinto, Ligia A.] Leidos Biomed Res Inc, Human Papillomavirus HPV Immunol Lab, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
[Safaeian, Mahboobeh] NCI, Bethesda, MD 20892 USA.
RP Pinto, LA (reprint author), Leidos Biomed Res Inc, Human Papillomavirus HPV Immunol Lab, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
EM pintol@mail.nih.gov
FU National Cancer Institute, National Institutes of Health
[HHSN261200800001E]
FX This project has been funded in whole or in part with federal funds from
the National Cancer Institute, National Institutes of Health, under
Contract No. HHSN261200800001E. The content of this publication does not
necessarily reflect the views or policies of the Department of Health
and Human Services, nor does mention of trade names, commercial
products, or organizations imply endorsement by the US. Government.
NR 40
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U1 2
U2 6
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 2164-5515
EI 2164-554X
J9 HUM VACC IMMUNOTHER
JI Human Vaccines Immunother.
PD FEB
PY 2015
VL 11
IS 2
BP 337
EP 346
DI 10.4161/21645515.2014.990851
PG 10
WC Biotechnology & Applied Microbiology; Immunology
SC Biotechnology & Applied Microbiology; Immunology
GA CF5RR
UT WOS:000352615200017
PM 25695397
ER
PT J
AU Gregory, S
Blair, RJ
Ffytche, D
Simmons, A
Kumari, V
Hodgins, S
Blackwood, N
AF Gregory, Sarah
Blair, R. James
Ffytche, Dominic
Simmons, Andrew
Kumari, Veena
Hodgins, Sheilagh
Blackwood, Nigel
TI Punishment and psychopathy: a case-control functional MRI investigation
of reinforcement learning in violent antisocial personality disordered
men
SO LANCET PSYCHIATRY
LA English
DT Article
ID VENTROMEDIAL PREFRONTAL CORTEX; DECISION-MAKING; RESPONSE REVERSAL;
GRAY-MATTER; INDIVIDUALS; OFFENDERS; DEFICITS; ACQUISITION; CHILDREN;
TRAITS
AB Background Men with antisocial personality disorder show lifelong abnormalities in adaptive decision making guided by the weighing up of reward and punishment information. Among men with antisocial personality disorder, modification of the behaviour of those with additional diagnoses of psychopathy seems particularly resistant to punishment.
Methods We did a case-control functional MRI (fMRI) study in 50 men, of whom 12 were violent off enders with antisocial personality disorder and psychopathy, 20 were violent off enders with antisocial personality disorder but not psychopathy, and 18 were healthy non-off enders. We used fMRI to measure brain activation associated with the representation of punishment or reward information during an event-related probabilistic response-reversal task, assessed with standard general linear-model-based analysis.
Findings Off enders with antisocial personality disorder and psychopathy displayed discrete regions of increased activation in the posterior cingulate cortex and anterior insula in response to punished errors during the task reversal phase, and decreased activation to all correct rewarded responses in the superior temporal cortex. This finding was in contrast to results for off enders without psychopathy and healthy non-off enders.
Interpretation Punishment prediction error signalling in off enders with antisocial personality disorder and psychopathy was highly atypical. This finding challenges the widely held view that such men are simply characterised by diminished neural sensitivity to punishment. Instead, this finding indicates altered organisation of the information-processing system responsible for reinforcement learning and appropriate decision making. This difference between violent off enders with antisocial personality disorder with and without psychopathy has implications for the causes of these disorders and for treatment approaches.
C1 [Gregory, Sarah; Blackwood, Nigel] Kings Coll London, Inst Psychiat, Dept Forens & Neurodev Sci, London SE5 8AF, England.
[Blair, R. James] NIMH, Mood & Anxiety Disorders Program, NIH, Bethesda, MD 20892 USA.
[Ffytche, Dominic] Kings Coll London, Inst Psychiat, Dept Old Age Psychiat, London SE5 8AF, England.
[Simmons, Andrew; Kumari, Veena] Kings Coll London, NIHR Biomed Res Ctr Mental Hlth South London, London SE5 8AF, England.
[Simmons, Andrew; Kumari, Veena] Kings Coll London, Maudsley NHS Fdn Trust, London SE5 8AF, England.
[Simmons, Andrew; Kumari, Veena] Kings Coll London, Inst Psychiat, London SE5 8AF, England.
[Hodgins, Sheilagh] Univ Montreal, Dept Psychiat, Montreal, PQ H3C 3J7, Canada.
RP Blackwood, N (reprint author), Kings Coll London, Inst Psychiat, Dept Forens & Neurodev Sci, POB 23,De Crespigny Pk, London SE5 8AF, England.
EM nigel.blackwood@kcl.ac.uk
RI Simmons, Andrew/B-8848-2008;
OI Simmons, Andrew/0000-0003-2306-5811; ffytche,
Dominic/0000-0002-4214-9642
FU National Forensic Mental Health Research and Development Programme; UK
Ministry of Justice; Psychiatry Research Trust; NIHR Biomedical Research
Centre
FX National Forensic Mental Health Research and Development Programme, UK
Ministry of Justice, Psychiatry Research Trust, NIHR Biomedical Research
Centre.
NR 38
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U1 5
U2 38
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 2215-0374
J9 LANCET PSYCHIAT
JI Lancet Psychiatry
PD FEB
PY 2015
VL 2
IS 2
BP 153
EP 160
PG 8
WC Psychiatry
SC Psychiatry
GA CF6ZP
UT WOS:000352705900020
PM 26359751
ER
PT J
AU Pacheco, J
Goh, JO
Kraut, MA
Ferrucci, L
Resnick, SM
AF Pacheco, Jennifer
Goh, Joshua O.
Kraut, Michael A.
Ferrucci, Luigi
Resnick, Susan M.
TI Greater cortical thinning in normal older adults predicts later
cognitive impairment
SO NEUROBIOLOGY OF AGING
LA English
DT Article
DE Alzheimer's disease; Cortical thinning; Early detection; Longitudinal;
Mild cognitive impairment
ID HUMAN CEREBRAL-CORTEX; ALZHEIMERS ASSOCIATION WORKGROUPS;
MAGNETIC-RESONANCE IMAGES; SURFACE-BASED ANALYSIS; MILD AD DEMENTIA;
GEOMETRICALLY ACCURATE; DIAGNOSTIC GUIDELINES; NATIONAL INSTITUTE;
COORDINATE SYSTEM; DISEASE
AB Cross-sectional studies have shown regional differences in cortical thickness between healthy older adults and patients with Alzheimer's disease (AD) or mild cognitive impairment (MCI). We now demonstrate that participants who subsequently develop cognitive impairment leading to a diagnosis of MCI or AD (n = 25) experience greater cortical thinning in specific neuroanatomic regions compared with control participants who remained cognitively normal (n = 96). Based on 8 years of annual magnetic resonance imaging scans beginning an average of 11 years before onset of cognitive impairment, participants who developed cognitive impairment subsequent to the scanning period had greater longitudinal cortical thinning in the temporal poles and left medial temporal lobe compared with controls. No significant regional cortical thickness differences were found at baseline between the 2 study groups indicating that we are capturing a critical time when brain changes occur before behavioral manifestations of impairment are detectable. Our findings suggest that early events of the pathway that leads to cognitive impairment may involve the temporal lobe and that this increased atrophy could be considered an early biomarker of neurodegeneration predictive of cognitive impairment years later. Published by Elsevier Inc.
C1 [Pacheco, Jennifer; Goh, Joshua O.; Ferrucci, Luigi; Resnick, Susan M.] NIA, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
[Goh, Joshua O.] Natl Taiwan Univ, Coll Med, Grad Inst Brain & Mind Sci, Taipei 10764, Taiwan.
[Kraut, Michael A.] Johns Hopkins Univ, Sch Med, Russell H Morgan Dept Radiol & Radiol Sci, Baltimore, MD USA.
RP Pacheco, J (reprint author), NIA, Intramural Res Program, NIH, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM jenni.pacheco@nih.gov
OI GOH, JOSHUA/0000-0001-7808-5452
FU Intramural Research Program of the National Institutes of Health,
National Institute on Aging; Research and Development Contract
[N01-AG-3-2124]
FX This research was supported in part by the Intramural Research Program
of the National Institutes of Health, National Institute on Aging, and
by Research and Development Contract N01-AG-3-2124. We are grateful to
the BLSA participants and staff for their dedication to these studies
and the staff of the Johns Hopkins MRI facility for their assistance.
NR 47
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U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0197-4580
EI 1558-1497
J9 NEUROBIOL AGING
JI Neurobiol. Aging
PD FEB
PY 2015
VL 36
IS 2
BP 903
EP 908
DI 10.1016/j.neurobiolaging.2014.08.031
PG 6
WC Geriatrics & Gerontology; Neurosciences
SC Geriatrics & Gerontology; Neurosciences & Neurology
GA CF3MZ
UT WOS:000352454400034
PM 25311277
ER
PT J
AU Bettcher, BM
Yaffe, K
Boudreau, RM
Neuhaus, J
Aizenstein, H
Ding, J
Kritchevsky, SB
Launer, LJ
Liu, Y
Satterfield, S
Rosano, C
AF Bettcher, Brianne Magouirk
Yaffe, Kristine
Boudreau, Robert M.
Neuhaus, John
Aizenstein, Howard
Ding, Jingzhong
Kritchevsky, Stephen B.
Launer, Lenore J.
Liu, Yongmei
Satterfield, Suzanne
Rosano, Caterina
CA Health ABC Study
TI Declines in inflammation predict greater white matter microstructure in
older adults
SO NEUROBIOLOGY OF AGING
LA English
DT Article
DE CRP; Pro-inflammatory; Diffusion tensor imaging; Longitudinal
ID C-REACTIVE PROTEIN; MILD COGNITIVE IMPAIRMENT; NECROSIS-FACTOR-ALPHA;
ALZHEIMERS-DISEASE; NEURODEGENERATIVE DISEASE; CARDIOVASCULAR-DISEASE;
VASCULAR DYSFUNCTION; DIFFUSION TENSOR; HEALTH ABC; TNF-ALPHA
AB Protracted systemic inflammation has been associated with adverse effects on cognition and brain structure and may accelerate neurodegenerative disease processes; however, it is less clear whether changes in inflammation are associated with brain structure. We studied 276 black and white older adults (mean age = 83 years at time of imaging) enrolled in a prospective study of aging. Inflammation (measured with c-reactive protein, CRP) was assessed repeatedly over 6 years (i.e., year 2, 4, 6, and 8). Brain magnetic resonance imaging (MRIs) were obtained at years 10-11 with diffusion tensor imaging; regions of interest included late-myelinating areas vulnerable to aging, including frontal-parietal (superior longitudinal fasciculus [SLF]-dorsal) and temporal (SLF-temporal; uncinate) white matter tracts. Mean CRP values significantly declined (t = -5.54, p < 0.0001) over 6 years, and subject-specific slopes (best linear unbiased predictors of slopes) all showed a decline (mean = -0.57, standard deviation = 0.53) for our participant sample. More than 50% of study participants were still in the moderate to high cardiovascular risk range based on CRP values at year 8. After controlling for demographics, vascular risk factors and MRI white matter hyperintensities, larger decreases in CRP values over time were significantly associated with higher fractional anisotropy in the SLF-dorsal (beta = -0.0052, standard error [SE] = 0.003; 95% confidence interval [CI] = -0.0103 to -0.0025, p = 0.04), SLF-temporal (beta = -0.0109, SE = 0.004; 95% CI = -0.0189 to -0.0029, p = 0.008), and uncinate (beta = -0.0067, SE = 0.003; 95% CI = -0.0132 to -0.0001, p = 0.05) fasciculi. Results suggest that in a prospective cohort of older individuals, faster declines in inflammation over time are related to indicators of white matter health, even after accounting for vascular risk factors. (C) 2015 Elsevier Inc. All rights reserved.
C1 [Bettcher, Brianne Magouirk; Neuhaus, John] Univ Calif San Francisco, Dept Neurol, Memory & Aging Ctr, San Francisco, CA 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] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
[Yaffe, Kristine] Univ Calif San Francisco, San Francisco VA Med Ctr, San Francisco, CA 94143 USA.
[Boudreau, Robert M.; Rosano, Caterina] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA.
[Aizenstein, Howard] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA.
[Ding, Jingzhong; Kritchevsky, Stephen B.; Liu, Yongmei] Wake Forest Sch Med, Sticht Ctr Aging, Winston Salem, NC USA.
[Launer, Lenore J.] NIA, Lab Epidemiol & Populat Sci, Bethesda, MD 20892 USA.
[Satterfield, Suzanne] Univ Tennessee, Ctr Hlth Sci, Dept Prevent Med, Memphis, TN 38163 USA.
RP Bettcher, BM (reprint author), Memory & Aging Ctr, Dept Neurol, 675 Nelson Rising Ln,Suite 190,MC 1207, San Francisco, CA 94158 USA.
EM bbettcher@memory.ucsf.edu
OI Rosano, Caterina/0000-0002-0909-1506; Rosano,
Caterina/0000-0002-4271-6010; Boudreau, Robert/0000-0003-0162-5187
FU National Institute on Aging (NIA) [N01-AG-6-2101, N01-AG-6-2103,
N01-AG-6-2106]; NIA [R01-AG028050, K23 AG042492-01, RO1-AG028288]; NINR
[R01-NR012459]; Intramural Research Program of the NIH, National
Institute on Aging; Alzheimer's Association [NIRP-12-259223]
FX This research was supported by National Institute on Aging (NIA)
Contracts N01-AG-6-2101; N01-AG-6-2103; N01-AG-6-2106; NIA grant
R01-AG028050, K23 AG042492-01 (Brianne Magouirk Bettcher), RO1-AG028288
(Yongmei Liu), and NINR grant R01-NR012459. This research was supported
in part by the Intramural Research Program of the NIH, National
Institute on Aging, as well as an Alzheimer's Association New
Investigator Grant (NIRP-12-259223; Brianne Magouirk Bettcher).
NR 56
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U1 1
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0197-4580
EI 1558-1497
J9 NEUROBIOL AGING
JI Neurobiol. Aging
PD FEB
PY 2015
VL 36
IS 2
BP 948
EP 954
DI 10.1016/j.neurobiolaging.2014.11.004
PG 7
WC Geriatrics & Gerontology; Neurosciences
SC Geriatrics & Gerontology; Neurosciences & Neurology
GA CF3MZ
UT WOS:000352454400040
PM 25554492
ER
PT J
AU Canugovi, C
Misiak, M
Scheibye-Knudsen, M
Croteau, DL
Mattson, MP
Bohr, VA
AF Canugovi, Chandrika
Misiak, Magdalena
Scheibye-Knudsen, Morten
Croteau, Deborah L.
Mattson, Mark P.
Bohr, Vilhelm A.
TI Loss of NEIL1 causes defects in olfactory function in mice
SO NEUROBIOLOGY OF AGING
LA English
DT Article
DE Aging, smell; Olfactory sense; DNA repair; Base excision repair;
Glycosylase; NEIL1; Oxidative stress; Oxidative DNA damage
ID BASE EXCISION-REPAIR; MILD COGNITIVE IMPAIRMENT; ALZHEIMERS-DISEASE;
PARKINSONS-DISEASE; DNA-REPAIR; NEURODEGENERATIVE DISEASES; BRAIN;
DYSFUNCTION; SYSTEM; RAT
AB Oxidative DNA damage accumulation has been implicated in neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. The base excision repair pathway is a primary responder to oxidative DNA damage. Effects of loss of base excision repair on normal brain function is a relatively nascent area of research that needs further exploration for better understanding of related brain diseases. Recently, we found that loss of a versatile DNA glycosylase endonuclease 8-like 1 (NEIL1) causes deficits in spatial memory retention using the Morris water maze test. Furthermore, we found that there is a significant loss of NEIL1 enzyme levels and its activity in postmortem Alzheimer's disease brains. Based on the Allen Brain Atlas in situ hybridization data, the expression levels of Neil1 messenger RNA are higher in the olfactory bulb compared with other areas of the brain. Olfaction in mice is a central brain function that involves many central nervous system pathways. Here, we studied the effect of complete loss of Neil1 gene on olfactory function. We explored olfactory function in mice with 3 different behavioral tests namely, olfactory sensitivity, performance, and buried food tests. Neil1(-/-) mice performed poorly compared with wild-type mice in all 3 tests. Our data indicate that loss of Neil1 causes olfactory function deficits supporting our previous findings and that normal brain function requires robust DNA repair. Published by Elsevier Inc.
C1 [Canugovi, Chandrika; Misiak, Magdalena; Scheibye-Knudsen, Morten; Croteau, Deborah L.; Bohr, Vilhelm A.] NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA.
[Misiak, Magdalena; Mattson, Mark P.] NIA, Neurosci Lab, NIH, Baltimore, MD 21224 USA.
RP Bohr, VA (reprint author), NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA.
EM vbohr@nih.gov
OI Scheibye-Knudsen, Morten/0000-0002-6637-1280
FU National Institute on Aging [AG000723-07]
FX Funding for this work is entirely provided by National Institute on
Aging, grant number AG000723-07. The authors thank Dr R. Stephen Lloyd
for the gift of NEIL1 knockout mice. They greatly appreciate Christopher
Morrell, NIA, for his help and advice with the statistical analysis of
our data. They thank Dr Baptiste Beverly and Dr Somnath Ghosh for
reading and revising the manuscript before submission.
NR 31
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U1 0
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0197-4580
EI 1558-1497
J9 NEUROBIOL AGING
JI Neurobiol. Aging
PD FEB
PY 2015
VL 36
IS 2
BP 1007
EP 1012
DI 10.1016/j.neurobiolaging.2014.09.026
PG 6
WC Geriatrics & Gerontology; Neurosciences
SC Geriatrics & Gerontology; Neurosciences & Neurology
GA CF3MZ
UT WOS:000352454400045
PM 25448603
ER
PT J
AU Scholz, SW
Majounie, E
Revesz, T
Holton, JL
Okun, MS
Houlden, H
Singleton, AB
AF Scholz, Sonja W.
Majounie, Elisa
Revesz, Tamas
Holton, Janice L.
Okun, Michael S.
Houlden, Henry
Singleton, Andrew B.
TI Multiple system atrophy is not caused by C9orf72 hexanucleotide repeat
expansions
SO NEUROBIOLOGY OF AGING
LA English
DT Article
DE Multiple system atrophy; C9orf72; Neurodegeneration; Amyotrophic lateral
sclerosis; Fronto-temporal dementia
AB Multiple system atrophy (MSA) is a fatal neurodegenerative disorder of unknown etiology that presents with variable combinations of progressive ataxia, parkinsonism, and autonomic instability. Pathologic expansion of a hexanucleotide repeat in the C9orf72 gene has been demonstrated to cause neuro-degeneration with diverse neurologic presentations. To test the hypothesis whether pathologic expansions in C9orf72 are a cause of MSA, we undertook genetic screening in 100 neuropathologically confirmed cases. No pathologic repeat expansions were detected suggesting that MSA is not a C9orf72-related neurodegenerative disease. Published by Elsevier Inc.
C1 [Scholz, Sonja W.] Johns Hopkins Univ Hosp, Dept Neurol, Baltimore, MD 20201 USA.
[Scholz, Sonja W.; Majounie, Elisa; Singleton, Andrew B.] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
[Revesz, Tamas; Holton, Janice L.; Houlden, Henry] UCL, Inst Neurol, Reta Lila Weston Labs, Dept Mol Neurosci, London, England.
[Okun, Michael S.] McKnight Brain Inst, UF Ctr Movement Disorders & Neurorestorat, Dept Neurol, Gainesville, FL USA.
RP Scholz, SW (reprint author), Johns Hopkins Univ Hosp, Dept Neurol, 1800 Orleans St, Baltimore, MD 20201 USA.
EM sscholz5@jhmi.edu
RI Houlden, Henry/C-1532-2008; Revesz, Tamas/A-8732-2010;
OI Houlden, Henry/0000-0002-2866-7777; Revesz, Tamas/0000-0003-2501-0259;
Okun, Michael/0000-0002-6247-9358; Scholz, Sonja/0000-0002-6623-0429
NR 0
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Z9 2
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0197-4580
EI 1558-1497
J9 NEUROBIOL AGING
JI Neurobiol. Aging
PD FEB
PY 2015
VL 36
IS 2
DI 10.1016/j.neurobiolaging.2014.08.033
PG 2
WC Geriatrics & Gerontology; Neurosciences
SC Geriatrics & Gerontology; Neurosciences & Neurology
GA CF3MZ
UT WOS:000352454400072
ER
PT J
AU Schottlaender, LV
Polke, JM
Ling, H
MacDoanld, ND
Tucci, A
Nanji, T
Pittman, A
de Silva, R
Holton, JL
Revesz, T
Sweeney, MG
Singleton, AB
Lees, AJ
Bhatia, KP
Houlden, H
AF Schottlaender, Lucia V.
Polke, James M.
Ling, Helen
MacDoanld, Nicola D.
Tucci, Arianna
Nanji, Tina
Pittman, Alan
de Silva, Rohan
Holton, Janice L.
Revesz, Tamas
Sweeney, Mary G.
Singleton, Andy B.
Lees, Andrew J.
Bhatia, Kailash P.
Houlden, Henry
TI The analysis of C9orf72 repeat expansions in a large series of
clinically and pathologically diagnosed cases with atypical parkinsonism
SO NEUROBIOLOGY OF AGING
LA English
DT Article
DE C9orf72; Parkinsonism; Multiple system atrophy (MSA); Progressive
supranuclear palsy (PSP); Corticobasal degeneration (CBD) and
corticobasal syndrome (CBS)
ID MULTIPLE-SYSTEM ATROPHY; PROGRESSIVE SUPRANUCLEAR PALSY;
AMYOTROPHIC-LATERAL-SCLEROSIS; FRONTOTEMPORAL LOBAR DEGENERATION;
HEXANUCLEOTIDE REPEAT; CORTICOBASAL DEGENERATION; PROGRANULIN MUTATION;
INCREASED RISK; SNCA VARIANTS; DISEASE
AB A GGGGCC repeat expansion in the C9orf72 gene was recently identified as a major cause of familial and sporadic amyotrophic lateral sclerosis and frontotemporal dementia. There is suggestion that these expansions may be a rare cause of parkinsonian disorders such as progressive supranuclear palsy (PSP), multiple system atrophy (MSA), and corticobasal degeneration (CBD). Screening the C9orf72 gene in 37 patients with features of corticobasal syndrome (CBS) detected an expansion in 3 patients, confirmed by Southern blotting. In a series of 22 patients with clinically diagnosed PSP, we found 1 patient with an intermediate repeat length. We also screened for the C9orf72 expansion in a large series of neuro-pathologically confirmed samples with MSA (n = 96), PSP (n = 177), and CBD (n = 18). Patients were found with no more than 22 GGGGCC repeats. Although these results still need to be confirmed in a larger cohort of CBS and/or CBD patients, these data suggest that in the presence of a family history and/or motor neuron disease features, patients with CBS or clinical PSP should be screened for the C9orf72 repeat expansion. In addition, we confirm that the C9orf72 expansions are not associated with pathologically confirmed MSA, PSP, or CBD in a large series of cases. (C) 2015 The Authors. Published by Elsevier Inc. All rights reserved.
C1 [Schottlaender, Lucia V.; Polke, James M.; Ling, Helen; Tucci, Arianna; Nanji, Tina; Pittman, Alan; de Silva, Rohan; Holton, Janice L.; Revesz, Tamas; Sweeney, Mary G.; Lees, Andrew J.; Houlden, Henry] Natl Hosp Neurol & Neurosurg, UCL Inst Neurol, Dept Mol Neurosci, London WC1N 3BG, England.
[Polke, James M.; Nanji, Tina; Sweeney, Mary G.; Houlden, Henry] Natl Hosp Neurol & Neurosurg, UCL Inst Neurol, Neurogenet Lab, London WC1N 3BG, England.
[Ling, Helen; Pittman, Alan; de Silva, Rohan; Holton, Janice L.; Revesz, Tamas; Lees, Andrew J.] Natl Hosp Neurol & Neurosurg, UCL Inst Neurol, Queen Sq Brain Bank, Reta Lila Weston Inst Neurol Studies, London WC1N 3BG, England.
[MacDoanld, Nicola D.; Houlden, Henry] Natl Hosp Neurol & Neurosurg, UCL Inst Neurol, MRC Ctr Neuromuscular Dis, London WC1N 3BG, England.
[Singleton, Andy B.] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
[Bhatia, Kailash P.] Natl Hosp Neurol & Neurosurg, UCL Inst Neurol, Sobell Dept Movement Disorders, London WC1N 3BG, England.
RP Houlden, H (reprint author), Natl Hosp Neurol & Neurosurg, UCL Inst Neurol, Dept Mol Neurosci, Queen Sq, London WC1N 3BG, England.
EM h.houlden@ucl.ac.uk
RI Pittman, Alan/D-6231-2012; Houlden, Henry/C-1532-2008
OI Houlden, Henry/0000-0002-2866-7777
FU Medical Research Council [G0802760]; Wellcome Trust/MRC Joint Call in
Neurodegeneration award [WT089698]; Brain Research Trust; National
Organization for Rare Disorders; MSA Trust; National Institutes of
Health (NIH) dystonia Coalition from ORDR in National Center for
Advancing Translational Sciences (NCATS) [NS065701]; National Institutes
of Neurological disorders and stroke (NINDS) as part of the NIH Rare
Diseases Clinical Research Network (RDCRN); Dystonia medical research
foundation (DMRF); National Institute for Health Research (NIHR)
University College London Hospitals (UCLH) Biomedical Research Centre
(BRC); Reta Lila Weston Trust for Medical Research
FX The authors thank the patients and their families for their help and
sample and brain donation. This study was supported by the Medical
Research Council (G0802760) and the Wellcome Trust/MRC Joint Call
(WT089698) in Neurodegeneration award (WT089698) as well as the Brain
Research Trust, National Organization for Rare Disorders, the MSA Trust,
the National Institutes of Health (NIH) dystonia Coalition funded by
NS065701 from ORDR in National Center for Advancing Translational
Sciences (NCATS) and National Institutes of Neurological disorders and
stroke (NINDS) as part of the NIH Rare Diseases Clinical Research
Network (RDCRN) and the Dystonia medical research foundation (DMRF). The
authors are grateful to the Queen Square Brain Bank, the Harvard Brain
Tissue Resource Centre, the Manchester Brain Bank, the The Eunice
Kennedy Shriver National Institute of Child Health and Human Development
(NICHD) Brain and Tissue Bank for Developmental Disorders, and the
Netherlands brain bank for provision of human tissue. This study was
also supported by the National Institute for Health Research (NIHR)
University College London Hospitals (UCLH) Biomedical Research Centre
(BRC), and the Reta Lila Weston Trust for Medical Research.
NR 51
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U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0197-4580
EI 1558-1497
J9 NEUROBIOL AGING
JI Neurobiol. Aging
PD FEB
PY 2015
VL 36
IS 2
DI 10.1016/j.neurobiolaging.2014.08.024
PG 6
WC Geriatrics & Gerontology; Neurosciences
SC Geriatrics & Gerontology; Neurosciences & Neurology
GA CF3MZ
UT WOS:000352454400067
ER
PT J
AU Simoncic, U
Zanotti-Fregonara, P
AF Simoncic, Urban
Zanotti-Fregonara, Paolo
TI Image-derived input function with factor analysis and a-priori
information
SO NUCLEAR MEDICINE COMMUNICATIONS
LA English
DT Article
DE [C-11](R)-rolipram; factor analysis; image-derived input function;
positron emission tomography
ID POSITRON-EMISSION-TOMOGRAPHY; MAJOR DEPRESSIVE DISORDER; BRAIN PET;
QUANTIFICATION; PHOSPHODIESTERASE-4; RADIOLIGAND; METHODOLOGY;
VALIDATION; RECEPTORS; ALGORITHM
AB Background Quantitative PET studies often require the cumbersome and invasive procedure of arterial cannulation to measure the input function. This study sought to minimize the number of necessary blood samples by developing a factor-analysis-based image-derived input function (IDIF) methodology for dynamic PET brain studies.
Materials and methods IDIF estimation was performed as follows: (a) carotid and background regions were segmented manually on an early PET time frame; (b) blood-weighted and tissue-weighted time-activity curves (TACs) were extracted with factor analysis; (c) factor analysis results were denoised and scaled using the voxels with the highest blood signal; (d) using population data and one blood sample at 40 min, whole-blood TAC was estimated from postprocessed factor analysis results; and (e) the parent concentration was finally estimated by correcting the whole-blood curve with measured radiometabolite concentrations. The methodology was tested using data from 10 healthy individuals imaged with [C-11](R)-rolipram. The accuracy of IDIFs was assessed against full arterial sampling by comparing the area under the curve of the input functions and by calculating the total distribution volume (V-T).
Results The shape of the image-derived whole-blood TAC matched the reference arterial curves well, and the whole-blood area under the curves were accurately estimated (mean error 1.0 +/- 4.3%). The relative Logan-V-T error was -4.1 +/- 6.4%. Compartmental modeling and spectral analysis gave less accurate V-T results compared with Logan.
Conclusion A factor-analysis-based IDIF for [C-11](R)-rolipram brain PET studies that relies on a single blood sample and population data can be used for accurate quantification of Logan-V-T values. Nucl Med Commun 36: 187-193 (C) 2015 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.
C1 [Simoncic, Urban] Jozef Stefan Inst, SI-1000 Ljubljana, Slovenia.
[Simoncic, Urban] Ctr Excellence Biosensors Instrumentat & Proc Con, Ajdovscina, Slovenia.
[Zanotti-Fregonara, Paolo] Univ Bordeaux, CNRS, INCIA, UMR 5287, Talence, France.
[Zanotti-Fregonara, Paolo] NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA.
RP Simoncic, U (reprint author), Jozef Stefan Inst, Jamova 39, SI-1000 Ljubljana, Slovenia.
EM urban.simoncic@gmail.com
OI Simoncic, Urban/0000-0002-5835-072X
FU Slovenian Research Agency (ARRS); Centre of Excellence for Biosensors,
Instrumentation, and Process Control; Intramural Research Program of the
National Institute of Mental Health, National Institutes of Health
(IRP-NIMH-NIH)
FX This work was supported by the Slovenian Research Agency (ARRS); the
Centre of Excellence for Biosensors, Instrumentation, and Process
Control and the Intramural Research Program of the National Institute of
Mental Health, National Institutes of Health (IRP-NIMH-NIH).
NR 29
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U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0143-3636
EI 1473-5628
J9 NUCL MED COMMUN
JI Nucl. Med. Commun.
PD FEB
PY 2015
VL 36
IS 2
BP 187
EP 193
DI 10.1097/MNM.0000000000000231
PG 7
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA CF7IV
UT WOS:000352730600013
PM 25321159
ER
PT J
AU Gonzalez, AR
Fee, E
AF Gonzalez, Ana Rita
Fee, Elizabeth
TI Anemia in Puerto Rico at the Turn of the Twentieth Century
SO AMERICAN JOURNAL OF PUBLIC HEALTH
LA English
DT Editorial Material
C1 [Gonzalez, Ana Rita] Policy Wisdom LLC, Miami, FL USA.
[Fee, Elizabeth] NIH, Natl Lib Med, Bethesda, MD 20892 USA.
RP Gonzalez, AR (reprint author), 9981 SW 143rd St, Miami, FL 33176 USA.
EM argonzalez@policywisdom.com; feee@mail.nlm.nih.gov
NR 5
TC 0
Z9 0
U1 0
U2 0
PU AMER PUBLIC HEALTH ASSOC INC
PI WASHINGTON
PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA
SN 0090-0036
EI 1541-0048
J9 AM J PUBLIC HEALTH
JI Am. J. Public Health
PD FEB
PY 2015
VL 105
IS 2
BP 272
EP 273
DI 10.2105/AJPH.2014.302225
PG 2
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA CE6CD
UT WOS:000351922500027
PM 25521874
ER
PT J
AU Garofalo, MF
Fee, E
AF Garofalo, Mary F.
Fee, Elizabeth
TI Lavinia Dock (1858-1956): Picketing, Parading, and Protesting
SO AMERICAN JOURNAL OF PUBLIC HEALTH
LA English
DT Editorial Material
C1 [Garofalo, Mary F.] NIH, Ctr Clin, Bethesda, MD 20892 USA.
[Fee, Elizabeth] NIH, Natl Lib Med, Bethesda, MD 20892 USA.
RP Fee, E (reprint author), Natl Lib Med, 8600 Rockville Pike,MSC 3819,Bldg 38,Room 1E21, Bethesda, MD 20894 USA.
EM feee@mail.nih.gov
NR 9
TC 0
Z9 0
U1 0
U2 1
PU AMER PUBLIC HEALTH ASSOC INC
PI WASHINGTON
PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA
SN 0090-0036
EI 1541-0048
J9 AM J PUBLIC HEALTH
JI Am. J. Public Health
PD FEB
PY 2015
VL 105
IS 2
BP 276
EP 277
DI 10.2105/AJPH.2014.302021
PG 2
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA CE6CD
UT WOS:000351922500029
PM 25521903
ER
PT J
AU Chawla, N
Breen, N
Liu, BM
Lee, R
Kagawa-Singer, M
AF Chawla, Neetu
Breen, Nancy
Liu, Benmei
Lee, Richard
Kagawa-Singer, Marjorie
TI Asian American Women in California: A Pooled Analysis of Predictors for
Breast and Cervical Cancer Screening
SO AMERICAN JOURNAL OF PUBLIC HEALTH
LA English
DT Article
ID PAP TEST USE; UNITED-STATES; VIETNAMESE-AMERICANS; PACIFIC ISLANDERS;
INCIDENCE TRENDS; CONTROLLED-TRIAL; HEALTH; CHINESE; DISPARITIES;
IMMIGRANTS
AB Objectives. We examined patterns of cervical and breast cancer screening among Asian American women in California and assessed their screening trends over time.
Methods. We pooled weighted data from 5 cycles of the California Health Interview Survey (2001, 2003, 2005, 2007, 2009) to examine breast and cervical cancer screening trends and predictors among 6 Asian nationalities. We calculated descriptive statistics, bivariate associations, multivariate logistic regressions, predictive margins, and 95% confidence intervals.
Results. Multivariate analyses indicated that Papanicolaou test rates did not significantly change over time (77.9% in 2001 vs 81.2% in 2007), but mammography receipt increased among Asian American women overall (75.6% in 2001 vs 81.8% in 2009). Length of time in the United States was associated with increased breast and cervical cancer screening among all nationalities. Socio-demographic and health care access factors had varied effects, with education and insurance coverage significantly predicting screening for certain groups. Overall, we observed striking variation by nationality.
Conclusions. Our results underscore the need for intervention and policy efforts that are targeted to specific Asian nationalities, recent immigrants, and individuals without health care access to increase screening rates among Asian women in California.
C1 [Chawla, Neetu] NCI, Outcomes Res Branch, Appl Res Program, Div Canc Control & Populat Sci, Rockville, MD 20850 USA.
[Breen, Nancy] NCI, Hlth Serv & Econ Branch, Appl Res Program, Div Canc Control & Populat Sci, Rockville, MD 20850 USA.
[Liu, Benmei] NCI, Stat Methodol & Applicat Branch, Surveillance Res Program, Div Canc Control & Populat Sci, Rockville, MD 20850 USA.
[Lee, Richard] Informat Management Serv Inc, Calverton, MD USA.
[Kagawa-Singer, Marjorie] Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA.
[Kagawa-Singer, Marjorie] Asian Amer Studies Dept, Los Angeles, CA USA.
RP Chawla, N (reprint author), NCI, Outcomes Res Branch, Appl Res Program, Div Canc Control & Populat Sci, 9609 Med Ctr Dr, Rockville, MD 20850 USA.
EM neetu.chawla@nih.gov
FU Cancer Prevention Fellowship Program
FX The authors would like to acknowledge the support of the Cancer
Prevention Fellowship Program for this research.
NR 64
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U1 3
U2 10
PU AMER PUBLIC HEALTH ASSOC INC
PI WASHINGTON
PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA
SN 0090-0036
EI 1541-0048
J9 AM J PUBLIC HEALTH
JI Am. J. Public Health
PD FEB
PY 2015
VL 105
IS 2
BP E98
EP E109
DI 10.2105/AJPH.2014.302250
PG 12
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA CE6CD
UT WOS:000351922500019
PM 25521898
ER
PT J
AU Kishi, S
Magalhaes, TA
George, RT
Dewey, M
Laham, RJ
Niinuma, H
Friedman, LA
Cox, C
Tanami, Y
Schuijf, JD
Vavere, AL
Kitagawa, K
Chen, MY
Nomura, CH
Brinker, JA
Rybicki, FJ
Di Carli, MF
Arbab-Zadeh, A
Lima, JAC
AF Kishi, Satoru
Magalhaes, Tiago A.
George, Richard T.
Dewey, Marc
Laham, Roger J.
Niinuma, Hiroyuki
Friedman, Lisa Aronson
Cox, Christopher
Tanami, Yutaka
Schuijf, Joanne D.
Vavere, Andrea L.
Kitagawa, Kakuya
Chen, Marcus Y.
Nomura, Cesar H.
Brinker, Jeffrey A.
Rybicki, Frank J.
Di Carli, Marcelo F.
Arbab-Zadeh, Armin
Lima, Joao A. C.
TI Relationship of left ventricular mass to coronary atherosclerosis and
myocardial ischaemia: the CORE320 multicenter study
SO EUROPEAN HEART JOURNAL-CARDIOVASCULAR IMAGING
LA English
DT Article
DE Coronary atherosclerosis; Left ventricular mass; Myocardial ischaemia;
Atheroma volume
ID ROW COMPUTED-TOMOGRAPHY; ARTERY-DISEASE; DIAGNOSTIC PERFORMANCE;
HYPERTENSIVE PATIENTS; MAGNETIC-RESONANCE; FLOW RESERVE; HYPERTROPHY;
ANGIOGRAPHY; PERFUSION; ECHOCARDIOGRAPHY
AB Aims The aim of this study was to investigate the association of left ventricular mass (LVM) with coronary atherosclerosis and myocardial infarction (MI).
Methods and results Patients (n = 338) underwent 320 x 0.5 mm detector row coronary computed tomography (CT) angiography, invasive coronary angiography (ICA), and single-photon emission CT (SPECT) myocardial perfusion imaging. Quantitative coronary atheroma volume was obtained from the CT images for the entire coronary tree (19-segment model) with an arterial contour detection algorithm. Normalized total atheroma volume (NormTAV) was analysed to reflect quantitative total atheroma volume. LVM was measured on myocardial CT images and indexed to height to the power of 2.7 (LVMi). Patients with obstructive coronary artery disease (CAD) were defined as those with >= 50% diameter stenosis by quantitative ICA. Abnormal perfusion defect was defined as = 1 abnormal myocardial segment by SPECT. The association of LVMi with coronary atherosclerosis and myocardial perfusion defect on SPECT at the patient level was determined with uni-and multivariable linear and logistic regression analyses. Obstructive CAD was present in 60.0% of enrolled patients. LVMi was independently associated with abnormal summed rest score [SRS; odds ratio (OR), 1.07; 95% confidence interval (CI), 1.03-1.09] and summed stress score (OR, 1.04; 95% CI, 1.01-1.07). An increase in LVMi was also independently associated with that in NormTAV (coefficient, 10.44; 95% CI, 1.50-19.39) and SRS = 1 (OR, 1.05; 95% CI, 1.01-1.10), even after adjusting for cardiovascular risk factors in patients without previous MI.
Conclusions LVM was independently associated with the presence of coronary artery atherosclerosis and MI.
C1 [Kishi, Satoru; Magalhaes, Tiago A.; George, Richard T.; Vavere, Andrea L.; Brinker, Jeffrey A.; Arbab-Zadeh, Armin; Lima, Joao A. C.] Johns Hopkins Univ, Div Cardiol, Dept Med, Sch Med, Baltimore, MD 21287 USA.
[Dewey, Marc] Humboldt Univ, Charite Med Sch, Dept Radiol, D-10099 Berlin, Germany.
[Dewey, Marc] Free Univ Berlin, Berlin, Germany.
[Laham, Roger J.] Beth Israel Deaconess Med Ctr, Div Cardiol, Boston, MA 02215 USA.
[Niinuma, Hiroyuki] St Lukes Int Hosp, Div Cardiol, Tokyo, Japan.
[Friedman, Lisa Aronson; Cox, Christopher] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Tanami, Yutaka] Keio Univ, Dept Radiol, Tokyo, Japan.
[Schuijf, Joanne D.] Toshiba Med Syst Europe BV, Zoetermeer, Netherlands.
[Kitagawa, Kakuya] Mie Univ Hosp, Dept Radiol, Tsu, Mie, Japan.
[Chen, Marcus Y.] NHLBI, Adv Cardiovasc Imaging Grp, NIH, Bethesda, MD 20892 USA.
[Nomura, Cesar H.] Hosp Israelita Albert Einstein, Radiol Sect, Sao Paulo, Brazil.
[Rybicki, Frank J.; Di Carli, Marcelo F.] Harvard Univ, Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA.
RP Lima, JAC (reprint author), Johns Hopkins Univ, Div Cardiol, Dept Med, Sch Med, Blalock 524,600 N Wolfe St, Baltimore, MD 21287 USA.
EM jlima@jhmi.edu
OI Dewey, Marc/0000-0002-4402-2733
FU CORE320 study, Toshiba Medical Systems Corporation
FX The sponsor of the CORE320 study, Toshiba Medical Systems Corporation,
was not involved during any stage of the planning, design, data
acquisition, data analysis, or manuscript preparation of this study.
NR 33
TC 1
Z9 2
U1 0
U2 3
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 FEB
PY 2015
VL 16
IS 2
BP 166
EP 176
DI 10.1093/ehjci/jeu217
PG 11
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA CE8GP
UT WOS:000352080200006
PM 25368207
ER
PT J
AU Warren, JL
Butler, EN
Stevens, J
Lathan, CS
Noone, AM
Ward, KC
Harlan, LC
AF Warren, Joan L.
Butler, Ebonee N.
Stevens, Jennifer
Lathan, Christopher S.
Noone, Anne-Michelle
Ward, Kevin C.
Harlan, Linda C.
TI Receipt of Chemotherapy Among Medicare Patients With Cancer by Type of
Supplemental Insurance
SO JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
ID UNITED-STATES; BENEFICIARIES; THERAPY; CARE; POPULATION; HOSPITALS;
TRENDS
AB Purpose
Medicare beneficiaries with cancer bear a greater portion of their health care costs, because cancer treatment costs have increased. Beneficiaries have supplemental insurance to reduce out-of-pocket costs; those without supplemental insurance may face barriers to care. This study examines the association between type of supplemental insurance coverage and receipt of chemotherapy among Medicare patients with cancer who, per National Comprehensive Cancer Network treatment guidelines, should generally receive chemotherapy.
Patients and Methods
This retrospective, observational study included 1,200 Medicare patients diagnosed with incident cancer of the breast (stage IIB to III), colon (stage III), rectum (stage II to III), lung (stage II to IV), or ovary (stage II to IV) from 2000 to 2005. Using the National Cancer Institute Patterns of Care Studies and linked SEER-Medicare data, we determined each Medicare patient's supplemental insurance status (private insurance, dual eligible [ie, Medicare with Medicaid], or no supplemental insurance), consultation with an oncologist, and receipt of chemotherapy. Using adjusted logistic regression, we evaluated the association of type of supplemental insurance with oncologist consultation and receipt of chemotherapy.
Results
Dual-eligible patients were significantly less likely to receive chemotherapy than were Medicare patients with private insurance. Patients with Medicare only who saw an oncologist had comparable rates of chemotherapy compared with Medicare patients with private insurance.
Conclusion
Dual-eligible Medicare beneficiaries received recommended cancer chemotherapy less frequently than other Medicare beneficiaries. With the increasing number of Medicaid patients under the Affordable Care Act, there will be a need for patient navigators and sufficient physician reimbursement so that low-income patients with cancer will have access to oncologists and needed treatment. (C) 2014 by American Society of Clinical Oncology
C1 [Warren, Joan L.; Noone, Anne-Michelle; Harlan, Linda C.] NCI, Bethesda, MD 20892 USA.
[Stevens, Jennifer] Informat Management Serv Inc, Beltsville, MD USA.
[Butler, Ebonee N.] Univ N Carolina, Chapel Hill, NC USA.
[Lathan, Christopher S.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Ward, Kevin C.] Emory Univ, Atlanta, GA 30322 USA.
RP Warren, JL (reprint author), NCI, Div Canc Control & Populat Sci, 9609 Med Ctr Dr,Room 3E428, Bethesda, MD 20892 USA.
EM joan_warren@nih.gov
FU NCI NIH HHS [P50 CA058223]
NR 23
TC 7
Z9 7
U1 0
U2 2
PU AMER SOC CLINICAL ONCOLOGY
PI ALEXANDRIA
PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA
SN 0732-183X
EI 1527-7755
J9 J CLIN ONCOL
JI J. Clin. Oncol.
PD FEB 1
PY 2015
VL 33
IS 4
BP 312
EP U191
DI 10.1200/JCO.2014.55.3107
PG 8
WC Oncology
SC Oncology
GA CF3BP
UT WOS:000352422900008
PM 25534387
ER
PT J
AU Bourne, PE
AF Bourne, Philip E.
TI Confronting the Ethical Challenges of Big Data in Public Health
SO PLOS COMPUTATIONAL BIOLOGY
LA English
DT Editorial Material
C1 NIH, Off Director, Bethesda, MD 20892 USA.
RP Bourne, PE (reprint author), NIH, Off Director, Bldg 10, Bethesda, MD 20892 USA.
EM philip.bourne@nih.gov
NR 4
TC 2
Z9 2
U1 4
U2 8
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-734X
EI 1553-7358
J9 PLOS COMPUT BIOL
JI PLoS Comput. Biol.
PD FEB
PY 2015
VL 11
IS 2
AR e1004073
DI 10.1371/journal.pcbi.1004073
PG 2
WC Biochemical Research Methods; Mathematical & Computational Biology
SC Biochemistry & Molecular Biology; Mathematical & Computational Biology
GA CE8GX
UT WOS:000352081000030
PM 25664660
ER
PT J
AU Edlefsen, PT
Rolland, M
Hertz, T
Tovanabutra, S
Gartland, AJ
Decamp, AC
Magaret, CA
Ahmed, H
Gottardo, R
Juraska, M
Mccoy, C
Larsen, BB
Sanders-Buell, E
Carrico, C
Menis, S
Bose, M
Arroyo, MA
O'Connell, RJ
Nitayaphan, S
Pitisuttithum, P
Kaewkungwal, J
Rerks-Ngarm, S
Robb, ML
Kirys, T
Georgiev, IS
Kwong, PD
Scheffler, K
Pond, SLK
Carlson, JM
Michael, NL
Schief, WR
Mullins, JI
Kim, JH
Gilbert, PB
AF Edlefsen, Paul T.
Rolland, Morgane
Hertz, Tomer
Tovanabutra, Sodsai
Gartland, Andrew J.
decamp, Allan C.
Magaret, Craig A.
Ahmed, Hasan
Gottardo, Raphael
Juraska, Michal
McCoy, Connor
Larsen, Brendan B.
Sanders-Buell, Eric
Carrico, Chris
Menis, Sergey
Bose, Meera
Arroyo, Miguel A.
O'Connell, Robert J.
Nitayaphan, Sorachai
Pitisuttithum, Punnee
Kaewkungwal, Jaranit
Rerks-Ngarm, Supachai
Robb, Merlin L.
Kirys, Tatsiana
Georgiev, Ivelin S.
Kwong, Peter D.
Scheffler, Konrad
Pond, Sergei L. Kosakovsky
Carlson, Jonathan M.
Michael, Nelson L.
Schief, William R.
Mullins, James I.
Kim, Jerome H.
Gilbert, Peter B.
CA RV144 Sequencing Team
TI Comprehensive Sieve Analysis of Breakthrough HIV-1 Sequences in the
RV144 Vaccine Efficacy Trial
SO PLOS COMPUTATIONAL BIOLOGY
LA English
DT Article
ID COMPETING RISKS; PEPTIDE BINDING; CELL RESPONSES; SUBTYPE-B; PROTEIN;
ENVELOPE; NEUTRALIZATION; EPITOPES; ESCAPE; GP120
AB The RV144 clinical trial showed the partial efficacy of a vaccine regimen with an estimated vaccine efficacy (VE) of 31% for protecting low-risk Thai volunteers against acquisition of HIV-1. The impact of vaccine-induced immune responses can be investigated through sieve analysis of HIV-1 breakthrough infections (infected vaccine and placebo recipients). A V1/V2-targeted comparison of the genomes of HIV-1 breakthrough viruses identified two V2 amino acid sites that differed between the vaccine and placebo groups. Here we extended the V1/V2 analysis to the entire HIV-1 genome using an array of methods based on individual sites, k-mers and genes/proteins. We identified 56 amino acid sites or "signatures" and 119 k-mers that differed between the vaccine and placebo groups. Of those, 19 sites and 38 k-mers were located in the regions comprising the RV144 vaccine (Env-gp120, Gag, and Pro). The nine signature sites in Env-gp120 were significantly enriched for known antibody-associated sites (p = 0.0021). In particular, site 317 in the third variable loop (V3) overlapped with a hotspot of antibody recognition, and sites 369 and 424 were linked to CD4 binding site neutralization. The identified signature sites significantly covaried with other sites across the genome (mean = 32.1) more than did non-signature sites (mean = 0.9) (p < 0.0001), suggesting functional and/or structural relevance of the signature sites. Since signature sites were not preferentially restricted to the vaccine immunogens and because most of the associations were insignificant following correction for multiple testing, we predict that few of the genetic differences are strongly linked to the RV144 vaccine-induced immune pressure. In addition to presenting results of the first complete-genome analysis of the breakthrough infections in the RV144 trial, this work describes a set of statistical methods and tools applicable to analysis of breakthrough infection genomes in general vaccine efficacy trials for diverse pathogens.
C1 [Edlefsen, Paul T.; Hertz, Tomer; Gartland, Andrew J.; decamp, Allan C.; Magaret, Craig A.; Ahmed, Hasan; Gottardo, Raphael; Juraska, Michal; McCoy, Connor; Gilbert, Peter B.] Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, Seattle, WA 98104 USA.
[Rolland, Morgane; Tovanabutra, Sodsai; Sanders-Buell, Eric; Bose, Meera; Robb, Merlin L.; Michael, Nelson L.; Kim, Jerome H.] US Mil HIV Res Program, Silver Spring, MD USA.
[Hertz, Tomer] Ben Gurion Univ Negev, Fac Hlth Sci, Shraga Segal Dept Microbiol Immunol & Genet, IL-84105 Beer Sheva, Israel.
[Hertz, Tomer] Ben Gurion Univ Negev, Natl Inst Biotechnol Negev, IL-84105 Beer Sheva, Israel.
[Larsen, Brendan B.; Mullins, James I.] Univ Washington, Dept Microbiol, Seattle, WA 98195 USA.
[Carrico, Chris; Menis, Sergey; Schief, William R.] Univ Washington, Dept Biochem, Seattle, WA 98195 USA.
[Carrico, Chris; Menis, Sergey; Schief, William R.] Scripps Res Inst, IAVI Neutralizing Antibody Ctr, La Jolla, CA 92037 USA.
[Carrico, Chris; Menis, Sergey; Schief, William R.] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA.
[Arroyo, Miguel A.; Nitayaphan, Sorachai; Kaewkungwal, Jaranit] AFRIMS, Royal Thai Army Component, Bangkok, Thailand.
[O'Connell, Robert J.] AFRIMS, US Army Component, Bangkok, Thailand.
[Pitisuttithum, Punnee] Mahidol Univ, Fac Trop Med, Bangkok, Thailand.
[Rerks-Ngarm, Supachai] Thai Minist Publ Hlth, CDC Dept, Nonthaburi, Thailand.
[Kirys, Tatsiana; Georgiev, Ivelin S.; Kwong, Peter D.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Scheffler, Konrad; Pond, Sergei L. Kosakovsky] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA.
[Carlson, Jonathan M.] Microsoft Res, eSience Res Grp, Redmond, WA USA.
[Schief, William R.] Ragon Inst MGH MIT & Harvard, Cambridge, MA 02139 USA.
RP Edlefsen, PT (reprint author), Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, 1124 Columbia St, Seattle, WA 98104 USA.
EM pedlefse@fredhutch.org
RI Hertz, Tomer/S-5744-2016
OI Hertz, Tomer/0000-0002-0561-1578
FU U.S. Army Medical Research and Material Command (USAMRMC)
[Y1-AI-2642-12]; National Institutes of Allergy and Infectious Diseases;
Department of Veterans Affairs, Veterans Health Administration, Office
of Research and development; Henry M. Jackson Foundation for the
Advancement of Military Medicine, Inc. [W81XWH-07-2-0067]; U.S.
Department of Defense (DOD) [W81XWH-07-2-0067]; Vaccine Research Center,
NIAID/NIH; NIH [2R37AI05465-11]
FX This study was supported in part by an Interagency Agreement
Y1-AI-2642-12 between U.S. Army Medical Research and Material Command
(USAMRMC), the National Institutes of Allergy and Infectious Diseases,
and by the Department of Veterans Affairs, Veterans Health
Administration, Office of Research and development. This work was also
supported by a cooperative agreement (W81XWH-07-2-0067) between the
Henry M. Jackson Foundation for the Advancement of Military Medicine,
Inc., and the U.S. Department of Defense (DOD). Additional support was
provided by Intramural funding of the Vaccine Research Center, NIAID/NIH
and to PBG through the NIH grant 2R37AI05465-11. The content is solely
the responsibility of the authors and does not necessarily represent the
official views of the U.S. Department of Health and Human Services,
National Institute for Allergy and Infectious Diseases, the Department
of the Army, the Department of Defense, or the Department of Veterans
Affairs. The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 57
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U1 1
U2 10
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-734X
EI 1553-7358
J9 PLOS COMPUT BIOL
JI PLoS Comput. Biol.
PD FEB
PY 2015
VL 11
IS 2
AR UNSP e1003973
DI 10.1371/journal.pcbi.1003973
PG 37
WC Biochemical Research Methods; Mathematical & Computational Biology
SC Biochemistry & Molecular Biology; Mathematical & Computational Biology
GA CE8GX
UT WOS:000352081000005
PM 25646817
ER
PT J
AU Erren, TC
Slanger, TE
Gross, JV
Bourne, PE
Cullen, P
AF Erren, Thomas C.
Slanger, Tracy E.
Gross, J. Valerie
Bourne, Philip E.
Cullen, Paul
TI Ten Simple Rules for Lifelong Learning, According to Hamming
SO PLOS COMPUTATIONAL BIOLOGY
LA English
DT Editorial Material
C1 [Erren, Thomas C.; Slanger, Tracy E.; Gross, J. Valerie] Univ Hosp Cologne, Inst & Policlin Occupat Med Environm Med & Preven, Cologne, Germany.
[Bourne, Philip E.] NIH, Off Director, Bethesda, MD 20892 USA.
[Cullen, Paul] Med Labor Munster, Munster, Germany.
RP Erren, TC (reprint author), Univ Hosp Cologne, Inst & Policlin Occupat Med Environm Med & Preven, Cologne, Germany.
EM tim.erren@uni-koeln.de
NR 16
TC 0
Z9 0
U1 12
U2 16
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-734X
EI 1553-7358
J9 PLOS COMPUT BIOL
JI PLoS Comput. Biol.
PD FEB
PY 2015
VL 11
IS 2
AR e1004020
DI 10.1371/journal.pcbi.1004020
PG 5
WC Biochemical Research Methods; Mathematical & Computational Biology
SC Biochemistry & Molecular Biology; Mathematical & Computational Biology
GA CE8GX
UT WOS:000352081000010
PM 25719205
ER
PT J
AU Lengauer, T
Nussinov, R
AF Lengauer, Thomas
Nussinov, Ruth
TI How to Write a Presubmission Inquiry
SO PLOS COMPUTATIONAL BIOLOGY
LA English
DT Editorial Material
C1 [Lengauer, Thomas] Max Planck Inst Informat, Dept Computat Biol & Appl Algorithm, D-66123 Saarbrucken, Germany.
[Nussinov, Ruth] NCI, Frederick Natl Lab Canc Res, Leidos Biomed Res Inc, Canc & Inflammat Program, Frederick, MD 21701 USA.
[Nussinov, Ruth] Tel Aviv Univ, Sackler Sch Med, Sackler Inst Mol Med, Dept Human Genet & Mol Med, IL-69978 Tel Aviv, Israel.
RP Lengauer, T (reprint author), Max Planck Inst Informat, Dept Computat Biol & Appl Algorithm, D-66123 Saarbrucken, Germany.
EM lengauer@mpi-inf.mpg.de
NR 0
TC 0
Z9 0
U1 0
U2 1
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-734X
EI 1553-7358
J9 PLOS COMPUT BIOL
JI PLoS Comput. Biol.
PD FEB
PY 2015
VL 11
IS 2
AR e1004098
DI 10.1371/journal.pcbi.1004098
PG 3
WC Biochemical Research Methods; Mathematical & Computational Biology
SC Biochemistry & Molecular Biology; Mathematical & Computational Biology
GA CE8GX
UT WOS:000352081000039
PM 25719491
ER
PT J
AU Meisel, C
Klaus, A
Kuehn, C
Plenz, D
AF Meisel, Christian
Klaus, Andreas
Kuehn, Christian
Plenz, Dietmar
TI Critical Slowing Down Governs the Transition to Neuron Spiking
SO PLOS COMPUTATIONAL BIOLOGY
LA English
DT Article
ID EARLY-WARNING SIGNALS; RAT SOMATOSENSORY CORTEX; PHASE RESETTING CURVES;
PYRAMIDAL NEURONS; CORTICAL-NEURONS; TIPPING POINT; IN-VIVO; DYNAMICS;
MODEL; EXCITABILITY
AB Many complex systems have been found to exhibit critical transitions, or so-called tipping points, which are sudden changes to a qualitatively different system state. These changes can profoundly impact the functioning of a system ranging from controlled state switching to a catastrophic break-down; signals that predict critical transitions are therefore highly desirable. To this end, research efforts have focused on utilizing qualitative changes in markers related to a system's tendency to recover more slowly from a perturbation the closer it gets to the transition-a phenomenon called critical slowing down. The recently studied scaling of critical slowing down offers a refined path to understand critical transitions: to identify the transition mechanism and improve transition prediction using scaling laws.
Here, we outline and apply this strategy for the first time in a real-world system by studying the transition to spiking in neurons of the mammalian cortex. The dynamical system approach has identified two robust mechanisms for the transition from subthreshold activity to spiking, saddle-node and Hopf bifurcation. Although theory provides precise predictions on signatures of critical slowing down near the bifurcation to spiking, quantitative experimental evidence has been lacking. Using whole-cell patch-clamp recordings from pyramidal neurons and fast-spiking interneurons, we show that 1) the transition to spiking dynamically corresponds to a critical transition exhibiting slowing down, 2) the scaling laws suggest a saddle-node bifurcation governing slowing down, and 3) these precise scaling laws can be used to predict the bifurcation point from a limited window of observation. To our knowledge this is the first report of scaling laws of critical slowing down in an experiment. They present a missing link for a broad class of neuroscience modeling and suggest improved estimation of tipping points by incorporating scaling laws of critical slowing down as a strategy applicable to other complex systems.
C1 [Meisel, Christian; Klaus, Andreas; Plenz, Dietmar] NIMH, Sect Crit Brain Dynam, Bethesda, MD 20892 USA.
[Meisel, Christian] Univ Clin Carl Gustav Carus, Dept Neurol, Dresden, Germany.
[Kuehn, Christian] Vienna Univ Technol, Inst Anal & Sci Comp, A-1040 Vienna, Austria.
RP Meisel, C (reprint author), NIMH, Sect Crit Brain Dynam, Bethesda, MD 20892 USA.
EM christian@meisel.de
RI Kuehn, Christian/H-3950-2014;
OI Kuehn, Christian/0000-0002-7063-6173; Klaus, Andreas/0000-0002-4133-351X
FU Intramural Research Program of the National Institute of Mental Health;
Austrian Academy of Sciences (OAW) via an APART fellowship; European
Commission (EC/REA)
FX This research was supported by the Intramural Research Program of the
National Institute of Mental Health. CK would like to thank the Austrian
Academy of Sciences (OAW) for support via an APART fellowship. CK also
acknowledges the European Commission (EC/REA) for support by a
Marie-Curie International Reintegration Grant. The funders had no role
in study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 63
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U1 3
U2 12
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-734X
EI 1553-7358
J9 PLOS COMPUT BIOL
JI PLoS Comput. Biol.
PD FEB
PY 2015
VL 11
IS 2
AR e1004097
DI 10.1371/journal.pcbi.1004097
PG 20
WC Biochemical Research Methods; Mathematical & Computational Biology
SC Biochemistry & Molecular Biology; Mathematical & Computational Biology
GA CE8GX
UT WOS:000352081000038
PM 25706912
ER
PT J
AU Che, J
Smith, S
Kim, YJ
Shim, EY
Myung, K
Lee, SE
AF Che, Jun
Smith, Stephanie
Kim, Yoo Jung
Shim, Eun Yong
Myung, Kyungjae
Lee, Sang Eun
TI Hyper-Acetylation of Histone H3K56 Limits Break-Induced Replication by
Inhibiting Extensive Repair Synthesis
SO PLOS GENETICS
LA English
DT Article
ID S-PHASE CHECKPOINT; DOUBLE-STRAND BREAKS; CONSERVATIVE DNA-SYNTHESIS;
CHROMATIN-ASSEMBLY FACTORS; H3 LYSINE-56 ACETYLATION;
SACCHAROMYCES-CEREVISIAE; CELL-CYCLE; CHROMOSOMAL REARRANGEMENTS;
HOMOLOGOUS RECOMBINATION; DAMAGE CHECKPOINT
AB Break-induced replication (BIR) has been implicated in restoring eroded telomeres and collapsed replication forks via single-ended invasion and extensive DNA synthesis on the recipient chromosome. Unlike other recombination subtypes, DNA synthesis in BIR likely relies heavily on mechanisms enabling efficient fork progression such as chromatin modification. Herein we report that deletion of HST3 and HST4, two redundant de-acetylases of histone H3 Lysine 56 (H3K56), inhibits BIR, sensitizes checkpoint deficient cells to deoxyribonucleotide triphosphate pool depletion, and elevates translocation-type gross chromosomal rearrangements (GCR). The basis for deficiency in BIR and gene conversion with long gap synthesis in hst3. hst4. cells can be traced to a defect in extensive DNA synthesis. Distinct from other cellular defects associated with deletion of HST3 and HST4 including thermo-sensitivity and elevated spontaneous mutagenesis, the BIR defect in hst3. hst4. cannot be offset by the deletion of RAD17 or MMS22, but rather by the loss of RTT109 or ASF1, or in combination with the H3K56R mutation, which also restores tolerance to replication stress in mrc1 mutants. Our studies suggest that acetylation of H3K56 limits extensive repair synthesis and interferes with efficient fork progression in BIR.
C1 [Che, Jun] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA.
[Che, Jun; Shim, Eun Yong; Lee, Sang Eun] Univ Texas Hlth Sci Ctr San Antonio, Dept Radiat Oncol, Program Radiat Biol, San Antonio, TX 78229 USA.
[Smith, Stephanie; Kim, Yoo Jung; Myung, Kyungjae] NHGRI, Genome Instabil Sect, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA.
[Shim, Eun Yong; Lee, Sang Eun] Univ Texas Hlth Sci Ctr San Antonio, Inst Biotechnol, Dept Mol Med, San Antonio, TX 78229 USA.
RP Che, J (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, San Antonio, TX 78229 USA.
EM lees4@uthscsa.edu
FU National Institute of Health [GM71011]; Cancer Prevention & Research
Institute of Texas [RP101491]; National Human Genome Research Institute
FX This work is supported by National Institute of Health research grant
GM71011 to SEL, Cancer Prevention & Research Institute of Texas Training
Grant RP101491 to JC, and the intramural Research Programs of the
National Human Genome Research Institute to KM. The funders had no role
in study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 70
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U1 2
U2 7
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7390
EI 1553-7404
J9 PLOS GENET
JI PLoS Genet.
PD FEB
PY 2015
VL 11
IS 2
AR e1004990
DI 10.1371/journal.pgen.1004990
PG 24
WC Genetics & Heredity
SC Genetics & Heredity
GA CE8HF
UT WOS:000352081800044
PM 25705897
ER
PT J
AU Didion, JP
Morgan, AP
Clayshulte, AMF
Mcmullan, RC
Yadgary, L
Petkov, PM
Bell, TA
Gatti, DM
Crowley, JJ
Hua, KJ
Aylor, DL
Bai, L
Calaway, M
Chesler, EJ
French, JE
Geiger, TR
Gooch, TJ
Garland, T
Harrill, AH
Hunter, K
McMillan, L
Holt, M
Miller, DR
O'Brien, DA
Paigen, K
Pan, WQ
Rowe, LB
Shaw, GD
Simecek, P
Sullivan, PF
Svenson, KL
Weinstock, GM
Threadgill, DW
Pomp, D
Churchill, GA
de Villena, FPM
AF Didion, John P.
Morgan, Andrew P.
Clayshulte, Amelia M. -F.
Mcmullan, Rachel C.
Yadgary, Liran
Petkov, Petko M.
Bell, Timothy A.
Gatti, Daniel M.
Crowley, James J.
Hua, Kunjie
Aylor, David L.
Bai, Ling
Calaway, Mark
Chesler, Elissa J.
French, John E.
Geiger, Thomas R.
Gooch, Terry J.
Garland, Theodore, Jr.
Harrill, Alison H.
Hunter, Kent
McMillan, Leonard
Holt, Matt
Miller, Darla R.
O'Brien, Deborah A.
Paigen, Kenneth
Pan, Wenqi
Rowe, Lucy B.
Shaw, Ginger D.
Simecek, Petr
Sullivan, Patrick F.
Svenson, Karen L.
Weinstock, George M.
Threadgill, David W.
Pomp, Daniel
Churchill, Gary A.
de Villena, Fernando Pardo-Manuel
TI A Multi-Megabase Copy Number Gain Causes Maternal Transmission Ratio
Distortion on Mouse Chromosome 2
SO PLOS GENETICS
LA English
DT Article
ID QUANTITATIVE TRAIT LOCI; MEIOTIC DRIVE; MUS-SPRETUS; HOUSE MOUSE;
CORRELATED RESPONSES; COLLABORATIVE CROSS; NATURAL-POPULATIONS;
LABORATORY MOUSE; GENETIC-CONTROL; MICE
AB Significant departures from expected Mendelian inheritance ratios (transmission ratio distortion, TRD) are frequently observed in both experimental crosses and natural populations. TRD on mouse Chromosome (Chr) 2 has been reported in multiple experimental crosses, including the Collaborative Cross (CC). Among the eight CC founder inbred strains, we found that Chr 2 TRD was exclusive to females that were heterozygous for the WSB/EiJ allele within a 9.3 Mb region (Chr 2 76.9 - 86.2 Mb). A copy number gain of a 127 kb-long DNA segment (designated as responder to drive, R2d) emerged as the strongest candidate for the causative allele. We mapped R2d sequences to two loci within the candidate interval. R2d1 is located near the proximal boundary, and contains a single copy of R2d in all strains tested. R2d2 maps to a 900 kb interval, and the number of R2d copies varies from zero in classical strains (including the mouse reference genome) to more than 30 in wild-derived strains. Using real-time PCR assays for the copy number, we identified a mutation (R2d2(WSBdel1)) that eliminates the majority of the R2d2(WSB) copies without apparent alterations of the surrounding WSB/EiJ haplotype. In a three-generation pedigree segregating for R2d2(WSBdel1), the mutation is transmitted to the progeny and Mendelian segregation is restored in females heterozygous for R2d2(WSBdel1), thus providing direct evidence that the copy number gain is causal for maternal TRD. We found that transmission ratios in R2d2(WSB) heterozygous females vary between Mendelian segregation and complete distortion depending on the genetic background, and that TRD is under genetic control of unlinked distorter loci. Although the R2d2(WSB) transmission ratio was inversely correlated with average litter size, several independent lines of evidence support the contention that female meiotic drive is the cause of the distortion. We discuss the implications and potential applications of this novel meiotic drive system.
C1 [Didion, John P.; Morgan, Andrew P.; Clayshulte, Amelia M. -F.; Mcmullan, Rachel C.; Yadgary, Liran; Bell, Timothy A.; Crowley, James J.; Hua, Kunjie; Calaway, Mark; Gooch, Terry J.; Miller, Darla R.; Shaw, Ginger D.; Sullivan, Patrick F.; Pomp, Daniel; de Villena, Fernando Pardo-Manuel] Univ N Carolina, Dept Genet, Chapel Hill, NC 27514 USA.
[Didion, John P.; Morgan, Andrew P.; Clayshulte, Amelia M. -F.; Mcmullan, Rachel C.; Bell, Timothy A.; Hua, Kunjie; Calaway, Mark; Gooch, Terry J.; Miller, Darla R.; O'Brien, Deborah A.; Pan, Wenqi; Shaw, Ginger D.; Pomp, Daniel; de Villena, Fernando Pardo-Manuel] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA.
[Didion, John P.; Morgan, Andrew P.; Clayshulte, Amelia M. -F.; Mcmullan, Rachel C.; Bell, Timothy A.; Hua, Kunjie; Calaway, Mark; Gooch, Terry J.; Miller, Darla R.; Shaw, Ginger D.; Pomp, Daniel; de Villena, Fernando Pardo-Manuel] Univ N Carolina, Carolina Ctr Genome Sci, Chapel Hill, NC USA.
[Petkov, Petko M.; Gatti, Daniel M.; Chesler, Elissa J.; Paigen, Kenneth; Rowe, Lucy B.; Simecek, Petr; Svenson, Karen L.; Churchill, Gary A.] Jackson Lab, Bar Harbor, ME 04609 USA.
[Hua, Kunjie; O'Brien, Deborah A.; Pan, Wenqi; Pomp, Daniel] Univ N Carolina, Dept Cell Biol & Physiol, Chapel Hill, NC USA.
[Aylor, David L.] N Carolina State Univ, Dept Biol Sci, Raleigh, NC 27695 USA.
[Bai, Ling; Geiger, Thomas R.; Hunter, Kent] NCI, Lab Canc Biol & Genet, NIH, Bethesda, MD 20892 USA.
[French, John E.] Natl Inst Environm Sci, Natl Toxicol Program, NIH, Res Triangle Pk, NC USA.
[Garland, Theodore, Jr.] Univ Calif Riverside, Dept Biol, Riverside, CA 92521 USA.
[Harrill, Alison H.] Univ Arkansas Med Sci, Dept Environm & Occupat Hlth, Little Rock, AR 72205 USA.
[McMillan, Leonard; Holt, Matt] Univ N Carolina, Dept Comp Sci, Chapel Hill, NC USA.
[Weinstock, George M.] Jackson Lab Genom Med, Farmington, CT USA.
[Threadgill, David W.] Texas A&M Univ, Dept Vet Pathobiol, College Stn, TX USA.
[Threadgill, David W.] Texas A&M Univ, Dept Mol & Cellular Med, College Stn, TX USA.
RP Didion, JP (reprint author), Univ N Carolina, Dept Genet, Chapel Hill, NC 27514 USA.
EM fernando@med.unc.edu
OI Crowley, James/0000-0001-9051-1557; Petkov, Petko/0000-0002-6694-9150;
Didion, John/0000-0002-8111-6261; McMullan, Rachel/0000-0003-0297-4549;
Morgan, Andrew Parker/0000-0003-1942-4543
FU National Institute of General Medical Sciences/National Institutes of
Health [GM076468, GM078452, 2P50GM076468-06]; National Institute of
Mental Health/National Institutes of Health [K01MH094406, 1R21
MH096261-01, 1F30 MH103925]; National Institute of Diabetes and
Digestive and Kidney Diseases/National Institutes of Health
[RC1DK087510, DK056350]; National Cancer Institute/National Institutes
of Health [ZIA BC011255, U01CA105417, R01CA079869, RC1 CA145504-02];
National Institute of Child Health and Human Development/National
Institutes of Health [R01HD065024]; NHGRI/National Institutes of Health
[R01 HG00941]; National Human Genome Research Institute/National
Institutes of Health [1U54 HG004968]; National Human Genome Research
Institute/National Institutes of Health - JAX interspecific backcross
panels; National Science Foundation [IOS-1121273]; Vaadia-BARD
Postdoctoral Fellowship Award from BARD, The United States - Israel
Binational Agricultural Research and Development Fund [FI-478-13]
FX We acknowledge grants National Institute of General Medical
Sciences/National Institutes of Health GM076468 and GM078452 (PMP);
National Institute of General Medical Sciences/National Institutes of
Health 2P50GM076468-06 (EJC, GAC); National Institute of Mental
Health/National Institutes of Health K01MH094406 (JJC); The National
Institute of Diabetes and Digestive and Kidney Diseases/National
Institutes of Health RC1DK087510 (DWT, AHH); National Cancer
Institute/National Institutes of Health ZIA BC011255 (KHun); National
Institute of Child Health and Human Development/National Institutes of
Health R01HD065024 (DAO, FPMdV); NHGRI/National Institutes of Health R01
HG00941 (LBR); National Cancer Institute/National Institutes of Health
U01CA105417 (DWT, DP); National Cancer Institute/National Institutes of
Health R01CA079869 (DWT); National Institute of Diabetes and Digestive
and Kidney Diseases/National Institutes of Health DK056350 (DP);
National Cancer Institute/National Institutes of Health RC1 CA145504-02
(GAC); National Institute of Mental Health/National Institutes of Health
1R21 MH096261-01 (FPMdV); National Institute of Mental Health/National
Institutes of Health 1F30 MH103925 (APM); National Human Genome Research
Institute/National Institutes of Health 1U54 HG004968 (GMW); National
Human Genome Research Institute/National Institutes of Health (funded
the JAX interspecific backcross panels); the National Science Foundation
IOS-1121273 (TG). This research was supported also by Vaadia-BARD
Postdoctoral Fellowship Award No. FI-478-13 from BARD, The United States
- Israel Binational Agricultural Research and Development Fund (LY). The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 81
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U2 9
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7404
J9 PLOS GENET
JI PLoS Genet.
PD FEB
PY 2015
VL 11
IS 2
AR e1004850
DI 10.1371/journal.pgen.1004850
PG 29
WC Genetics & Heredity
SC Genetics & Heredity
GA CE8HF
UT WOS:000352081800002
PM 25679959
ER
PT J
AU Kim, YJ
Igiesuorobo, O
Ramos, CI
Bao, H
Zhang, B
Serpe, M
AF Kim, Young-Jun
Igiesuorobo, Oghomwen
Ramos, Cathy I.
Bao, Hong
Zhang, Bing
Serpe, Mihaela
TI Prodomain Removal Enables Neto to Stabilize Glutamate Receptors at the
Drosophila Neuromuscular Junction
SO PLOS GENETICS
LA English
DT Article
ID PROCESSING PROTEASE PC2; SYNAPTIC DEVELOPMENT; PROPROTEIN CONVERTASES;
RETROGRADE SIGNAL; KAINATE RECEPTORS; SUBUNIT; PLASTICITY;
EMBRYOGENESIS; MELANOGASTER; SYNAPSES
AB Stabilization of neurotransmitter receptors at postsynaptic specializations is a key step in the assembly of functional synapses. Drosophila Neto (Neuropillin and Tolloid-like protein) is an essential auxiliary subunit of ionotropic glutamate receptor (iGluR) complexes required for the iGluRs clustering at the neuromuscular junction (NMJ). Here we show that optimal levels of Neto are crucial for stabilization of iGluRs at synaptic sites and proper NMJ development. Genetic manipulations of Neto levels shifted iGluRs distribution to extrajunctional locations. Perturbations in Neto levels also produced small NMJs with reduced synaptic transmission, but only Neto-depleted NMJs showed diminished postsynaptic components. Drosophila Neto contains an inhibitory prodomain that is processed by Furin1-mediated limited proteolysis. neto null mutants rescued with a Neto variant that cannot be processed have severely impaired NMJs and reduced iGluRs synaptic clusters. Unprocessed Neto retains the ability to engage iGluRs in vivo and to form complexes with normal synaptic transmission. However, Neto prodomain must be removed to enable iGluRs synaptic stabilization and proper postsynaptic differentiation.
C1 [Kim, Young-Jun; Igiesuorobo, Oghomwen; Ramos, Cathy I.; Serpe, Mihaela] NICHD, Program Cellular Regulat & Metab, NIH, Bethesda, MD 20892 USA.
[Bao, Hong; Zhang, Bing] Univ Missouri, Div Biol Sci, Columbia, MO 65211 USA.
RP Kim, YJ (reprint author), NICHD, Program Cellular Regulat & Metab, NIH, Bethesda, MD 20892 USA.
EM mihaela.serpe@nih.gov
FU National Institutes of Health, Eunice Kennedy Shriver National Institute
of Child Health & Human Development [ZIA-HD008869, ZIA-HD008914];
National Institutes of Health, National Institute of Neurological
Disorders and Stroke [RO1-NS060878]
FX The work performed in Serpe laboratory was funded by the Intramural
Research Program of the National Institutes of Health, Eunice Kennedy
Shriver National Institute of Child Health & Human Development (projects
ZIA-HD008869 and ZIA-HD008914, awarded to MS)
(https://www.nichd.nih.gov/about/org/dir/Pages/index.aspx). The work
performed in Zhang laboratory was funded by the National Institutes of
Health, National Institute of Neurological Disorders and Stroke (grant #
RO1-NS060878, awarded to BZ) (http://www.ninds.nih.gov/). The funders
had no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 77
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PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7390
EI 1553-7404
J9 PLOS GENET
JI PLoS Genet.
PD FEB
PY 2015
VL 11
IS 2
AR e1004988
DI 10.1371/journal.pgen.1004988
PG 26
WC Genetics & Heredity
SC Genetics & Heredity
GA CE8HF
UT WOS:000352081800042
PM 25723514
ER
PT J
AU Lageix, S
Zhang, JW
Rothenburg, S
Hinnebusch, AG
AF Lageix, Sebastien
Zhang, Jinwei
Rothenburg, Stefan
Hinnebusch, Alan G.
TI Interaction between the tRNA-Binding and C-Terminal Domains of Yeast
Gcn2 Regulates Kinase Activity In Vivo
SO PLOS GENETICS
LA English
DT Article
ID UNCHARGED TRANSFER-RNA; ACID-STARVED CELLS; PROTEIN-KINASE; AMINO-ACID;
TRANSLATION INITIATION; SACCHAROMYCES-CEREVISIAE; CRYSTAL-STRUCTURES;
ACTIVATION; SYNTHETASE; ASSOCIATION
AB The stress-activated protein kinase Gcn2 regulates protein synthesis by phosphorylation of translation initiation factor eIF2 alpha. Gcn2 is activated in amino acid-deprived cells by binding of uncharged tRNA to the regulatory domain related to histidyl-tRNA synthetase, but the molecular mechanism of activation is unclear. We used a genetic approach to identify a key regulatory surface in Gcn2 that is proximal to the predicted active site of the HisRS domain and likely remodeled by tRNA binding. Mutations leading to amino acid substitutions on this surface were identified that activate Gcn2 at low levels of tRNA binding (Gcd(-) phenotype), while other substitutions block kinase activation (Gcn(-) phenotype), in some cases without altering tRNA binding by Gcn2 in vitro. Remarkably, the Gcn(-) substitutions increase affinity of the HisRS domain for the C-terminal domain (CTD), previously implicated as a kinase autoinhibitory segment, in a manner dampened by HisRS domain Gcd(-) substitutions and by amino acid starvation in vivo. Moreover, tRNA specifically antagonizes HisRS/CTD association in vitro. These findings support a model wherein HisRS-CTD interaction facilitates the autoinhibitory function of the CTD in nonstarvation conditions, with tRNA binding eliciting kinase activation by weakening HisRS-CTD association with attendant disruption of the autoinhibitory KD-CTD interaction.
C1 [Lageix, Sebastien; Hinnebusch, Alan G.] Eunice K Shriver Natl Inst Child Hlth & Human Dev, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA.
[Zhang, Jinwei] NHLBI, NIH, Bethesda, MD 20892 USA.
[Rothenburg, Stefan] Kansas State Univ, Div Biol, Manhattan, KS 66506 USA.
RP Lageix, S (reprint author), Eunice K Shriver Natl Inst Child Hlth & Human Dev, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA.
EM ahinnebusch@nih.gov
FU National Institutes of Health
FX This research was supported by the Intramural Program of the National
Institutes of Health. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 52
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U1 0
U2 4
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PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7390
EI 1553-7404
J9 PLOS GENET
JI PLoS Genet.
PD FEB
PY 2015
VL 11
IS 2
AR e1004991
DI 10.1371/journal.pgen.1004991
PG 28
WC Genetics & Heredity
SC Genetics & Heredity
GA CE8HF
UT WOS:000352081800045
PM 25695491
ER
PT J
AU Schneider, A
Henegar, C
Day, K
Absher, D
Napolitano, C
Silveira, L
David, VA
O'Brien, SJ
Menotti-Raymond, M
Barsh, GS
Eizirik, E
AF Schneider, Alexsandra
Henegar, Corneliu
Day, Kenneth
Absher, Devin
Napolitano, Constanza
Silveira, Leandro
David, Victor A.
O'Brien, Stephen J.
Menotti-Raymond, Marilyn
Barsh, Gregory S.
Eizirik, Eduardo
TI Recurrent Evolution of Melanism in South American Felids
SO PLOS GENETICS
LA English
DT Article
ID HAPLOTYPE STRUCTURE; POSITIVE SELECTION; ONCIFELIS-GUIGNA; COAT COLOR;
GENOME; GENETICS; HISTORY; CAT; HYBRIDIZATION; PIGMENTATION
AB Morphological variation in natural populations is a genomic test bed for studying the interface between molecular evolution and population genetics, but some of the most interesting questions involve non-model organisms that lack well annotated reference genomes. Many felid species exhibit polymorphism for melanism but the relative roles played by genetic drift, natural selection, and interspecies hybridization remain uncertain. We identify mutations of Agouti signaling protein (ASIP) or the Melanocortin 1 receptor (MC1R) as independent causes of melanism in three closely related South American species: the pampas cat (Leopardus colocolo), the kodkod (Leopardus guigna), and Geoffroy's cat (Leopardus geoffroyi). To assess population level variation in the regions surrounding the causative mutations we apply genomic resources from the domestic cat to carry out clone-based capture and targeted resequencing of 299 kb and 251 kb segments that contain ASIP and MC1R, respectively, from 54 individuals (13-21 per species), achieving enrichment of similar to 500-2500-fold and similar to 150x coverage. Our analysis points to unique evolutionary histories for each of the three species, with a strong selective sweep in the pampas cat, a distinctive but short melanism-specific haplotype in the Geoffroy's cat, and reduced nucleotide diversity for both ancestral and melanism-bearing chromosomes in the kodkod. These results reveal an important role for natural selection in a trait of longstanding interest to ecologists, geneticists, and the lay community, and provide a platform for comparative studies of morphological variation in other natural populations.
C1 [Schneider, Alexsandra; Eizirik, Eduardo] Pontificia Univ Catolica Rio Grande Sul PUCRS, Fac Biociencias, Lab Biol Genom & Mol, Porto Alegre, RS, Brazil.
[Henegar, Corneliu; Day, Kenneth; Absher, Devin; Barsh, Gregory S.] HudsonAlpha Inst Biotechnol, Huntsville, AL USA.
[Napolitano, Constanza] Univ Chile, Lab Ecol Mol, Santiago, Chile.
[Napolitano, Constanza] Univ Chile, Fac Ciencias, Dept Ciencias Ecol, Inst Ecol & Biodiversidad, Santiago, Chile.
[Silveira, Leandro] Inst Onca Pintada, Jaguar Conservat Fund, Mineiros, Go, Brazil.
[David, Victor A.; Menotti-Raymond, Marilyn] NCI, Basic Res Lab, Frederick Natl Lab, Ctr Canc Res, Frederick, MD 21701 USA.
[O'Brien, Stephen J.] St Petersburg State Univ, Theodosius Dobzhansky Ctr Genome Informat, St Petersburg 199034, Russia.
[Eizirik, Eduardo] Inst Procarnivoros, Sao Paulo, Brazil.
RP Schneider, A (reprint author), Pontificia Univ Catolica Rio Grande Sul PUCRS, Fac Biociencias, Lab Biol Genom & Mol, Porto Alegre, RS, Brazil.
EM gbarsh@hudsonalpha.org; eduardo.eizirik@pucrs.br
RI Eizirik, Eduardo/K-8034-2012
OI Eizirik, Eduardo/0000-0002-9658-0999
FU Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq),
Brazil; Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior
(CAPES), Brazil; Intramural Research Program of the NIH; Frederick
National Laboratory; Center for Cancer Research; National Cancer
Institute; HudsonAlpha Institute for Biotechnology
FX This study was supported by Conselho Nacional de Desenvolvimento
Cientifico e Tecnologico (CNPq), Brazil, Coordenacao de Aperfeicoamento
de Pessoal de Nivel Superior (CAPES), Brazil, the Intramural Research
Program of the NIH, Frederick National Laboratory, Center for Cancer
Research, National Cancer Institute, and the HudsonAlpha Institute for
Biotechnology. The funders had no role in study design, data collection
and analysis, decision to publish, or preparation of the manuscript.
NR 48
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Z9 4
U1 4
U2 23
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7390
EI 1553-7404
J9 PLOS GENET
JI PLoS Genet.
PD FEB
PY 2015
VL 11
IS 2
AR e1004892
DI 10.1371/journal.pgen.1004892
PG 19
WC Genetics & Heredity
SC Genetics & Heredity
GA CE8HF
UT WOS:000352081800006
PM 25695801
ER
PT J
AU Radtke, AJ
Kastenmuller, W
Espinosa, DA
Gerner, MY
Tse, SW
Sinnis, P
Germain, RN
Zavala, FP
Cockburn, IA
AF Radtke, Andrea J.
Kastenmueller, Wolfgang
Espinosa, Diego A.
Gerner, Michael Y.
Tse, Sze-Wah
Sinnis, Photini
Germain, Ronald N.
Zavala, Fidel P.
Cockburn, Ian A.
TI Lymph-Node Resident CD8 alpha(+) Dendritic Cells Capture Antigens from
Migratory Malaria Sporozoites and Induce CD8(+) T Cell Responses
SO PLOS PATHOGENS
LA English
DT Article
ID PLASMODIUM-BERGHEI; IN-VIVO; CIRCUMSPOROZOITE PROTEIN; LIVER-STAGES;
LANGERHANS CELLS; IMMUNE-RESPONSE; IRRADIATED SPOROZOITES; PROTECTIVE
ANTIGEN; PRESENTING CELLS; DC SUBSETS
AB Malaria infection begins when a female Anopheles mosquito injects Plasmodium sporozoites into the skin of its host during blood feeding. Skin-deposited sporozoites may enter the bloodstream and infect the liver, reside and develop in the skin, or migrate to the draining lymph nodes (DLNs). Importantly, the DLN is where protective CD8(+) T cell responses against malaria liver stages are induced after a dermal route of infection. However, the significance of parasites in the skin and DLN to CD8(+) T cell activation is largely unknown. In this study, we used genetically modified parasites, as well as antibody-mediated immobilization of sporozoites, to determine that active sporozoite migration to the DLNs is required for robust CD8(+) T cell responses. Through dynamic in vivo and static imaging, we show the direct uptake of parasites by lymph-node resident DCs followed by CD8(+) T cell-DC cluster formation, a surrogate for antigen presentation, in the DLNs. A few hours after sporozoite arrival to the DLNs, CD8(+) T cells are primed by resident CD8 alpha(+) DCs with no apparent role for skin-derived DCs. Together, these results establish a critical role for lymph node resident CD8 alpha(+) DCs in CD8(+) T cell priming to sporozoite antigens while emphasizing a requirement for motile sporozoites in the induction of CD8(+) T cell-mediated immunity.
C1 [Radtke, Andrea J.; Espinosa, Diego A.; Tse, Sze-Wah; Sinnis, Photini; Zavala, Fidel P.; Cockburn, Ian A.] Johns Hopkins Malaria Res Inst, Baltimore, MD USA.
[Radtke, Andrea J.; Espinosa, Diego A.; Tse, Sze-Wah; Sinnis, Photini; Zavala, Fidel P.; Cockburn, Ian A.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD USA.
[Kastenmueller, Wolfgang; Gerner, Michael Y.; Germain, Ronald N.] NIAID, Lymphocyte Biol Sect, Lab Syst Biol, NIH, Bethesda, MD 20892 USA.
RP Radtke, AJ (reprint author), NIAID, Lymphocyte Biol Sect, Lab Syst Biol, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM fzavala@jhsph.edu; ian.cockburn@anu.edu.au
FU NIH [AI44375, AI056840]; Johns Hopkins Malaria Research Institute;
Bloomberg Family; NIAID, NIH
FX FPZ is supported by NIH grant AI44375. AJR was supported by a
pre-doctoral fellowship from the Johns Hopkins Malaria Research
Institute. PS is supported by NIH grant AI056840. The authors are
grateful for the support of the Bloomberg Family. This work was
supported in part by the Intramural Research Program of NIAID, NIH. The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 76
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U1 2
U2 11
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7366
EI 1553-7374
J9 PLOS PATHOG
JI PLoS Pathog.
PD FEB
PY 2015
VL 11
IS 2
AR e1004637
DI 10.1371/journal.ppat.1004637
PG 23
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA CE8HU
UT WOS:000352083400024
PM 25658939
ER
PT J
AU Wickner, RB
Edskes, HK
Bateman, DA
Gorkovskiy, A
Dayani, Y
Bezsonov, EE
Mukhamedova, M
AF Wickner, Reed B.
Edskes, Herman K.
Bateman, David A.
Gorkovskiy, Anton
Dayani, Yaron
Bezsonov, Evgeny E.
Mukhamedova, Maryam
TI Yeast Prions: Proteins Templating Conformation and an Anti-prion System
SO PLOS PATHOGENS
LA English
DT Article
ID SACCHAROMYCES-CEREVISIAE; URE3 PRION; STRAINS; MECHANISM; DISEASES; PSI+
C1 [Wickner, Reed B.; Edskes, Herman K.; Bateman, David A.; Gorkovskiy, Anton; Dayani, Yaron; Bezsonov, Evgeny E.; Mukhamedova, Maryam] Natl Inst Diabet & Digest & Kidney Dis, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA.
RP Wickner, RB (reprint author), Natl Inst Diabet & Digest & Kidney Dis, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA.
EM wickner@helix.nih.gov
RI Gorkovskiy, Anton/J-8930-2016
OI Gorkovskiy, Anton/0000-0003-4811-2282
FU National Institute of Diabetes and Digestive and Kidney Diseases of the
National Institutes of Health
FX This work was supported by the Intramural Program of the National
Institute of Diabetes and Digestive and Kidney Diseases of the National
Institutes of Health. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 27
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U1 2
U2 5
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7366
EI 1553-7374
J9 PLOS PATHOG
JI PLoS Pathog.
PD FEB
PY 2015
VL 11
IS 2
AR e1004584
DI 10.1371/journal.ppat.1004584
PG 5
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA CE8HU
UT WOS:000352083400005
PM 25654539
ER
PT J
AU McKinstry-Wu, AR
Bu, WM
Rai, G
Lea, WA
Weiser, BP
Liang, DF
Simeonov, A
Jadhav, A
Maloney, DJ
Eckenhoff, RG
AF McKinstry-Wu, Andrew R.
Bu, Weiming
Rai, Ganesha
Lea, Wendy A.
Weiser, Brian P.
Liang, David F.
Simeonov, Anton
Jadhav, Ajit
Maloney, David J.
Eckenhoff, Roderic G.
TI Discovery of a Novel General Anesthetic Chemotype Using High-throughput
Screening
SO ANESTHESIOLOGY
LA English
DT Article
ID GABA(A) RECEPTOR; TRANSMEMBRANE DOMAIN; BINDING-SITES; IDENTIFICATION;
AGONISTS
AB Background: The development of novel anesthetics has historically been a process of combined serendipity and empiricism, with most recent new anesthetics developed via modification of existing anesthetic structures.
Methods: Using a novel high-throughput screen employing the fluorescent anesthetic 1-aminoanthracene and apoferritin as a surrogate for on-pathway anesthetic protein target(s), we screened a 350,000 compound library for competition with 1-aminoanthracene-apoferritin binding. Hit compounds meeting structural criteria had their binding affinities for apoferritin quantified with isothermal titration calorimetry and were tested for.-aminobutyric acid type A receptor binding using a flunitrazepam binding assay. Chemotypes with a strong presence in the top 700 and exhibiting activity via isothermal titration calorimetry were selected for medicinal chemistry optimization including testing for anesthetic potency and toxicity in an in vivo Xenopus laevis tadpole assay. Compounds with low toxicity and high potency were tested for anesthetic potency in mice.
Results: From an initial chemical library of more than 350,000 compounds, we identified 2,600 compounds that potently inhibited 1-aminoanthracene binding to apoferritin. A subset of compounds chosen by structural criteria (700) was successfully reconfirmed using the initial assay. Based on a strong presence in both the initial and secondary screens the 6-phenylpyridazin-3(2H)-one chemotype was assessed for anesthetic activity in tadpoles. Medicinal chemistry efforts identified four compounds with high potency and low toxicity in tadpoles, two were found to be effective novel anesthetics in mice.
Conclusion: The authors demonstrate the first use of a high-throughput screen to successfully identify a novel anesthetic chemotype and show mammalian anesthetic activity for members of that chemotype.
C1 [McKinstry-Wu, Andrew R.; Bu, Weiming; Eckenhoff, Roderic G.] Univ Penn, Dept Anesthesiol & Crit Care, Philadelphia, PA 19104 USA.
[Weiser, Brian P.] Univ Penn, Dept Pharmacol, Philadelphia, PA 19104 USA.
[Rai, Ganesha; Lea, Wendy A.; Simeonov, Anton; Jadhav, Ajit; Maloney, David J.] NIH, Chem Genom Ctr, Natl Ctr Adv Translat Sci, Bethesda, MD 20892 USA.
[Liang, David F.] Univ Penn, Coll Arts & Sci, Philadelphia, PA 19104 USA.
RP Eckenhoff, RG (reprint author), Univ Penn, Dept Anesthesiol & Crit Care, 311A John Morgan Bldg,3620 Hamilton Walk, Philadelphia, PA 19104 USA.
EM roderic.eckenhoff@uphs.upenn.edu
FU National Institutes of Health (Bethesda, Maryland) through the Small
Grant Program [R03 MH 084836]; Program Project Grant [P01 GM 55876];
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, National
Institutes of Health, Bethesda, Maryland [U54MH084681]
FX Drs. McKinstry-Wu, Bu, Weiser, and Eckenhoff were supported by the
National Institutes of Health (Bethesda, Maryland) through the Small
Grant Program (R03 MH 084836) and a Program Project Grant (P01 GM
55876). Drs. Rai, Lea, Simenov, Jadhav, and Maloney 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,
National Institutes of Health, Bethesda, Maryland). The remaining
authors or their institutions have no intellectual property rights
regarding the compounds generated by this reported research.
NR 28
TC 3
Z9 4
U1 2
U2 8
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0003-3022
EI 1528-1175
J9 ANESTHESIOLOGY
JI Anesthesiology
PD FEB
PY 2015
VL 122
IS 2
BP 325
EP 333
DI 10.1097/ALN.0000000000000505
PG 9
WC Anesthesiology
SC Anesthesiology
GA CE3NZ
UT WOS:000351734900012
PM 25603205
ER
PT J
AU Zheng, CY
Chang, K
Suh, YH
Roche, KW
AF Zheng, Chan-Ying
Chang, Kai
Suh, Young Ho
Roche, Katherine W.
TI TARP gamma-8 glycosylation regulates the surface expression of AMPA
receptors
SO BIOCHEMICAL JOURNAL
LA English
DT Article
DE AMPA receptor; CNIH-2; N-linked glycosylation; TARP gamma-2; TARP
gamma-8; trafficking
ID AUXILIARY SUBUNITS; SYNAPTIC PLASTICITY; GLUTAMATE RECEPTORS; CORNICHON
PROTEINS; MUTANT MOUSE; HIPPOCAMPAL; TRAFFICKING; STARGAZIN; NEURONS;
SPINES
AB TARP [transmembrane AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptor regulatory protein] gamma-8 is an auxiliary subunit of AMPA receptors that is widely distributed in the hippocampus. It has been shown that TARP gamma-8 promotes surface expression of AMPA receptors; however, how TARP gamma-8 regulates the expression of AMPA receptors remains unclear. In the present study, we examined the effect of TARP glycosylation on AMPA receptor trafficking. We first showed that TARP gamma-8 is an N-glycosylated protein, which contains two glycosylation sites, Asn(53) and Asn(56), and compared this with the glycosylation of TARP gamma-2 and the AMPA receptor auxiliary protein CNIH-2 (cornichon homologue 2). We next examine the effect of TARP glycosylation on TARP trafficking and also on AMPA receptor surface expression. We find that TARP gamma-8 glycosylation is critical for surface expression of both TARP gamma-8 and GluA1 in heterologous cells and neurons. Specifically, knockdown of TARP gamma-8 causes a decrease in both total and surface AMPA receptors. We find that the expression of unglycosylated TARP gamma-8 in cultured neurons is unable to restore GluA1 expression fully. Furthermore, when the maturation of TARP gamma-8 is impaired, a large pool of immature GluA1 is retained intracellularly. Taken together, our data reveal an important role for the maturation of TARP gamma-8 in the trafficking and function of the AMPA receptor complex.
C1 [Zheng, Chan-Ying; Chang, Kai; Roche, Katherine W.] NINDS, Receptor Biol Sect, NIH, Bethesda, MD 20892 USA.
[Suh, Young Ho] Seoul Natl Univ, Coll Med, Dept Biomed Sci, Seoul 110799, South Korea.
RP Suh, YH (reprint author), Seoul Natl Univ, Coll Med, Dept Biomed Sci, Seoul 110799, South Korea.
EM suhyho@snu.ac.kr; rochek@ninds.nih.gov
FU National Institute of Neurological Disorders and Stroke Intramural
Research Program; Basic Science Research Program through the National
Research Foundation of Korea [NRF-2011-0011694]
FX This work was supported by the National Institute of Neurological
Disorders and Stroke Intramural Research Program. Y.H.S. was supported
by the Basic Science Research Program [grant number NRF-2011-0011694]
through the National Research Foundation of Korea.
NR 37
TC 3
Z9 3
U1 0
U2 1
PU PORTLAND PRESS LTD
PI LONDON
PA CHARLES DARWIN HOUSE, 12 ROGER STREET, LONDON WC1N 2JU, ENGLAND
SN 0264-6021
EI 1470-8728
J9 BIOCHEM J
JI Biochem. J.
PD FEB 1
PY 2015
VL 465
BP 471
EP 477
DI 10.1042/BJ20140806
PN 3
PG 7
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA CE2XV
UT WOS:000351686200011
PM 25495042
ER
PT J
AU Okoli, TC
Peer, CJ
Dunleavy, K
Figg, WD
AF Okoli, Tracy C.
Peer, Cody J.
Dunleavy, Kieron
Figg, William D.
TI Targeted PI3K delta inhibition by the small molecule idelalisib as a
novel therapy in indolent non-Hodgkin lymphoma
SO CANCER BIOLOGY & THERAPY
LA English
DT Article
DE B-cell chronic lymphocytic leukemia; follicular lymphoma; Furman etal;
Gopal etal; indolent Non-Hogkin Lymphoma; idelalisb; PI3K Inhibition;
rituximab; small lymphocytic lymphoma; targeted therapy
ID CHRONIC LYMPHOCYTIC-LEUKEMIA; RITUXIMAB; CLL
AB Indolent Non-Hodgkin Lymphomas (iNHL) are typically B-cell malignancies and are incurable with current standard approaches. Thus, there is a demand for novel agents specific for this group of disorders. In a phase II study published by Gopal etal. in the New England Journal of Medicine, idelalisib, a small molecule inhibitor of PI3K that was FDA approved in July of 2014, was shown to be effective when combined with rituximab in patients who cannot tolerate chemotherapy and as last line therapy in patients with iNHL refractory to 2 prior systemic therapies. Idelalisib demonstrated tolerable diarrhea, fatigue, nausea, pyrexia, and cough. While this novel agent is a clinically significant addition to the iNHL arsenal, further research is needed to determine its most appropriate place in iNHL therapy.
C1 [Okoli, Tracy C.; Peer, Cody J.; Figg, William D.] NCI, Clin Pharmacol Program, Ctr Canc Res, Bethesda, MD 20892 USA.
[Dunleavy, Kieron] NCI, Lymphoid Malignancies Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Figg, WD (reprint author), NCI, Clin Pharmacol Program, Ctr Canc Res, Bethesda, MD 20892 USA.
EM wf13e@nih.gov
RI Figg Sr, William/M-2411-2016
NR 14
TC 2
Z9 2
U1 0
U2 2
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 1538-4047
EI 1555-8576
J9 CANCER BIOL THER
JI Cancer Biol. Ther.
PD FEB
PY 2015
VL 16
IS 2
BP 204
EP 206
DI 10.1080/15384047.2014.1002369
PG 3
WC Oncology
SC Oncology
GA CE2FZ
UT WOS:000351631200005
PM 25756507
ER
PT J
AU Chao, CC
Karabanov, AN
Paine, R
de Campos, AC
Kukke, SN
Wu, TX
Wang, H
Hallett, M
AF Chao, Chi-Chao
Karabanov, Anke Ninija
Paine, Rainer
de Campos, Ana Carolina
Kukke, Sahana N.
Wu, Tianxia
Wang, Han
Hallett, Mark
TI Induction of Motor Associative Plasticity in the Posterior Parietal
Cortex-Primary Motor Network
SO CEREBRAL CORTEX
LA English
DT Article
DE associative plasticity; corticocortical paired-associative stimulation;
motor cortex; parietal motor connectivity; posterior parietal cortex
ID TRANSCRANIAL MAGNETIC STIMULATION; TIMING-DEPENDENT PLASTICITY;
THETA-BURST STIMULATION; EVENT-RELATED FMRI; CORTICOCORTICAL
CONNECTIONS; SOMATOSENSORY CORTEX; HIPPOCAMPAL-NEURONS;
PARKINSONS-DISEASE; DECISION-MAKING; HUMAN BRAIN
AB There is anatomical and functional connectivity between the primary motor cortex (M1) and posterior parietal cortex (PPC) that plays a role in sensorimotor integration. In this study, we applied corticocortical paired-associative stimuli to ipsilateral PPC and M1 (parietal ccPAS) in healthy right-handed subjects to test if this procedure could modulate M1 excitability and PPC-M1 connectivity. One hundred and eighty paired transcranial magnetic stimuli to the PPC and M1 at an interstimulus interval (ISI) of 8 ms were delivered at 0.2 Hz. We found that parietal ccPAS in the left hemisphere increased the excitability of conditioned left M1 assessed by motor evoked potentials (MEPs) and the input-output curve. Motor behavior assessed by the Purdue pegboard task was unchanged compared with controls. At baseline, conditioning stimuli over the left PPC potentiated MEPs from left M1 when ISI was 8 ms. This interaction significantly attenuated at 60 min after left parietal ccPAS. Additional experiments showed that parietal ccPAS induced plasticity was timing-dependent, was absent if ISI was 100 ms, and could also be seen in the right hemisphere. Our results suggest that parietal ccPAS can modulate M1 excitability and PPC-M1 connectivity and is a new approach to modify motor excitability and sensorimotor interaction.
C1 [Chao, Chi-Chao; Karabanov, Anke Ninija; Paine, Rainer; de Campos, Ana Carolina; Kukke, Sahana N.; Wang, Han; Hallett, Mark] NINDS, Human Motor Control Sect, Med Neurol Branch, NIH, Bethesda, MD 20892 USA.
[Wu, Tianxia] NIH, Ctr Informat Technol, Bethesda, MD 20892 USA.
[Chao, Chi-Chao] Natl Taiwan Univ Hosp, Dept Neurol, Taipei 100, Taiwan.
[Karabanov, Anke Ninija] Hvidovre Univ Hosp, Danish Res Ctr Magnet Resonance, DK-2650 Hvidovre, Denmark.
[Karabanov, Anke Ninija] Univ Copenhagen, Dept Exercise & Sport Sci, DK-2200 Copenhagen, Denmark.
[Wang, Han] Beijing Union Med Coll Hosp, Dept Neurol, Beijing, Peoples R China.
RP Hallett, M (reprint author), NINDS, Human Motor Control Sect, Med Neurol Branch, NIH, Bldg 10,Rm 7D37, Bethesda, MD 20892 USA.
EM hallettm@ninds.nih.gov
OI Karabanov, Anke Ninija/0000-0003-1874-393X
FU National Institute of Neurological Disorder and Stroke, National
Institutes of Health
FX This work was supported by (in part) by the Intramural Research Program
of the National Institute of Neurological Disorder and Stroke, National
Institutes of Health.
NR 71
TC 9
Z9 9
U1 1
U2 6
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 FEB
PY 2015
VL 25
IS 2
BP 365
EP 373
DI 10.1093/cercor/bht230
PG 9
WC Neurosciences
SC Neurosciences & Neurology
GA CE6GR
UT WOS:000351935300008
PM 23968834
ER
PT J
AU Faucz, FR
Horvath, AD
Azevedo, MF
Levy, I
Bak, B
Wang, Y
Xekouki, P
Szarek, E
Gourgari, E
Manning, AD
de Alexandre, RB
Saloustros, E
Trivellin, G
Lodish, M
Hofman, P
Anderson, YC
Holdaway, I
Oldfield, E
Chittiboina, P
Nesterova, M
Biermasz, NR
Wit, JM
Bernard, DJ
Stratakis, CA
AF Faucz, Fabio R.
Horvath, Anelia D.
Azevedo, Monalisa F.
Levy, Isaac
Bak, Beata
Wang, Ying
Xekouki, Paraskevi
Szarek, Eva
Gourgari, Evgenia
Manning, Allison D.
de Alexandre, Rodrigo Bertollo
Saloustros, Emmanouil
Trivellin, Giampaolo
Lodish, Maya
Hofman, Paul
Anderson, Yvonne C.
Holdaway, Ian
Oldfield, Edward
Chittiboina, Prashant
Nesterova, Maria
Biermasz, Nienke R.
Wit, Jan M.
Bernard, Daniel J.
Stratakis, Constantine A.
TI Is IGSF1 involved in human pituitary tumor formation?
SO ENDOCRINE-RELATED CANCER
LA English
DT Article
DE pituitary tumor; IGSF1; growth hormone; overgrowth; acromegaly;
gigantism
ID CONGENITAL CENTRAL HYPOTHYROIDISM; MUTATIONS; GIGANTISM; ADENOMAS
AB IGSF1 is a membrane glycoprotein highly expressed in the anterior pituitary. Pathogenic mutations in the IGSF1 gene (on Xq26.2) are associated with X-linked central hypothyroidism and testicular enlargement in males. In this study, we tested the hypothesis that IGSF1 is involved in the development of pituitary tumors, especially those that produce growth hormone (GH). IGSF1 was sequenced in 21 patients with gigantism or acromegaly and 92 healthy individuals. Expression studies with a candidate pathogenic IGSF1 variant were carried out in transfected cells and immunohistochemistry for IGSF1 was performed in the sections of GH-producing adenomas, familial somatomammotroph hyperplasia, and in normal pituitary. We identified the sequence variant p.N604T, which in silico analysis suggested could affect IGSF1 function, in two male patients and one female with somatomammotroph hyperplasia from the same family. Of 60 female controls, two carried the same variant and seven were heterozygous for other variants. Immunohistochemistry showed increased IGSF1 staining in the GH-producing tumor from the patient with the IGSF1 p. N604T variant compared with a GH-producing adenoma from a patient negative for any IGSF1 variants and with normal control pituitary tissue. The IGSF1 gene appears polymorphic in the general population. A potentially pathogenic variant identified in the germline of three patients with gigantism from the same family (segregating with the disease) was also detected in two healthy female controls. Variations in IGSF1 expression in pituitary tissue in patients with or without IGSF1 germline mutations point to the need for further studies of IGSF1 action in pituitary adenoma formation.
C1 [Faucz, Fabio R.; Horvath, Anelia D.; Azevedo, Monalisa F.; Levy, Isaac; Xekouki, Paraskevi; Szarek, Eva; Gourgari, Evgenia; Manning, Allison D.; de Alexandre, Rodrigo Bertollo; Saloustros, Emmanouil; Trivellin, Giampaolo; Lodish, Maya; Nesterova, Maria; Stratakis, Constantine A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrinol & Genet, Program Dev Endocrinol & Genet PDEGEN, NIH,Clin Res Ctr, Bethesda, MD 20892 USA.
[Faucz, Fabio R.; de Alexandre, Rodrigo Bertollo] Pontificia Univ Catolica Parana, Sch Med, Grp Adv Mol Invest, Grad Program Hlth Sci, BR-80215 Curitiba, Parana, Brazil.
[Bak, Beata; Wang, Ying; Bernard, Daniel J.] McGill Univ, Dept Pharmacol & Therapeut, Montreal, PQ H3G 1Y6, Canada.
[Gourgari, Evgenia; Stratakis, Constantine A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pediat Endocrinol Interinst Training Program, NIH, Bethesda, MD 20892 USA.
[Hofman, Paul; Anderson, Yvonne C.] Univ Auckland, Liggins Inst, Auckland 1023, New Zealand.
[Anderson, Yvonne C.] Taranaki Base Hosp, New Plymouth 4310, New Zealand.
[Holdaway, Ian] Auckland City Hosp, Auckland 1142, New Zealand.
[Holdaway, Ian] Greenlane Clin Ctr, Auckland 1142, New Zealand.
[Oldfield, Edward] Univ Virginia, Hlth Sci Ctr, Dept Neurosurg, Charlottesville, VA 22904 USA.
[Chittiboina, Prashant] NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA.
[Biermasz, Nienke R.] Leiden Univ, Med Ctr, Dept Endocrinol & Metab Disorders, NL-2333 Leiden, Netherlands.
[Wit, Jan M.] Leiden Univ, Med Ctr, Dept Pediat, NL-2333 Leiden, Netherlands.
RP Stratakis, CA (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrinol & Genet, Program Dev Endocrinol & Genet PDEGEN, NIH,Clin Res Ctr, 10 Ctr Dr,Bldg 10,Room 1-3330,MSC1103, Bethesda, MD 20892 USA.
EM stratakc@mail.nih.gov
RI de Alexandre, Rodrigo/H-9489-2013; Trivellin, Giampaolo/J-6583-2016;
OI de Alexandre, Rodrigo/0000-0002-1253-7716; Trivellin,
Giampaolo/0000-0003-2384-4153; Saloustros, Emmanouil
/0000-0002-0485-0120
FU Intramural Research Program, Eunice Kennedy Shriver National Institute
of Child Health & Human Development (NICHD), National Institutes of
Health (NIH); CNPq; University of Brasilia, Brazil; Conselho Nacional de
Desenvolvimento Cientifico e Tecnologico (CNPq) [Process: 311166/2011-3
- PQ-2]; Government of Canada-Canadian Institutes of Health Research
[CIHR MOP-133557]
FX This study was supported by the Intramural Research Program, Eunice
Kennedy Shriver National Institute of Child Health & Human Development
(NICHD), National Institutes of Health (NIH) (to C A Stratakis).
Additional support was provided from a post-doctoral fellowship grant
from CNPq and from the University of Brasilia, Brazil (to MF Azevedo;
mentor: Dr CA Stratakis), in part, by a grant from the Conselho Nacional
de Desenvolvimento Cientifico e Tecnologico (CNPq), Process:
311166/2011-3 - PQ-2 (to Fabio Rueda Faucz), and in part by a grant from
Government of Canada-Canadian Institutes of Health Research, grant
number CIHR MOP-133557 (to D J Bernard).
NR 15
TC 5
Z9 5
U1 0
U2 5
PU BIOSCIENTIFICA LTD
PI BRISTOL
PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT,
ENGLAND
SN 1351-0088
EI 1479-6821
J9 ENDOCR-RELAT CANCER
JI Endocr.-Relat. Cancer
PD FEB
PY 2015
VL 22
IS 1
BP 47
EP 54
DI 10.1530/ERC-14-0465
PG 8
WC Oncology; Endocrinology & Metabolism
SC Oncology; Endocrinology & Metabolism
GA CE7FD
UT WOS:000352002500013
PM 25527509
ER
PT J
AU Toledo, RA
Hatakana, R
Lourenco, DM
Lindsey, SC
Camacho, CP
Almeida, M
Lima, JV
Sekiya, T
Garralda, E
Naslavsky, MS
Yamamoto, GL
Lazar, M
Meirelles, O
Sobreira, TJP
Lebrao, ML
Duarte, YAO
Blangero, J
Zatz, M
Cerutti, JM
Maciel, RMB
Toledo, SPA
AF Toledo, Rodrigo A.
Hatakana, Roxanne
Lourenco, Delmar M., Jr.
Lindsey, Susan C.
Camacho, Cleber P.
Almeida, Marcio
Lima, Jose V., Jr.
Sekiya, Tomoko
Garralda, Elena
Naslavsky, Michel S.
Yamamoto, Guilherme L.
Lazar, Monize
Meirelles, Osorio
Sobreira, Tiago J. P.
Lebrao, Maria Lucia
Duarte, Yeda A. O.
Blangero, John
Zatz, Mayana
Cerutti, Janete M.
Maciel, Rui M. B.
Toledo, Sergio P. A.
TI Comprehensive assessment of the disputed RET Y791F variant shows no
association with medullary thyroid carcinoma susceptibility
SO ENDOCRINE-RELATED CANCER
LA English
DT Article
DE multiple endocrine neoplasias; RET oncogene; MEN2; medullary thyroid
carcinoma; genetics
ID ENDOCRINE NEOPLASIA TYPE-2; GENOTYPE-PHENOTYPE CORRELATION;
HIRSCHSPRUNG-DISEASE; PROTOONCOGENE MUTATIONS; GERMLINE MUTATIONS;
CANCER; SEQUENCE; FAMILIES; CODON-790/791; PENETRANCE
AB Accurate interpretation of germline mutations of the rearranged during transfection (RET) proto-oncogene is vital for the proper recommendation of preventive thyroidectomy in medullary thyroid carcinoma (MTC)-prone carriers. To gain information regarding the most disputed variant of RET, ATA-A Y791F, we sequenced blood DNA samples from a cohort of 2904 cancer-free elderly individuals (1261 via Sanger sequencing and 1643 via whole-exome/genome sequencing). We also accessed the exome sequences of an additional 8069 individuals from non-cancer-related laboratories and public databanks as well as genetic results from the Catalogue of Somatic Mutations in Cancer (COSMIC) project. The mean allelic frequency observed in the controls was 0.0031, with higher occurrences in Central European populations (0.006/0.008). The prevalence of RET Y791F in the control databases was extremely high compared with the 40 known RET pathogenic mutations (P=0.00003), while no somatic occurrence has been reported in tumours. In this study, we report new, unrelated Brazilian individuals with germline RET Y791F-only: two tumour-free elderly controls; two individuals with sporadic MTC whose Y791F-carrying relatives did not show any evidence of tumours; and a 74-year-old phaeochromocytoma patient without MTC. Furthermore, we showed that the co-occurrence of Y791F with the strong RET C634Y mutation explains the aggressive MTC phenotypes observed in a large affected family that was initially reported as Y791F-only. Our literature review revealed that limited analyses have led to the misclassification of RET Y791F as a probable pathogenic variant and, consequently, to the occurrence of unnecessary thyroidectomies. The current study will have a substantial clinical influence, as it reveals, in a comprehensive manner, that RET Y791F only shows no association with MTC susceptibility.
C1 [Toledo, Rodrigo A.; Hatakana, Roxanne; Lourenco, Delmar M., Jr.; Sekiya, Tomoko; Toledo, Sergio P. A.] Univ Sao Paulo, Sch Med, Hosp Clin, Endocrine Genet Unit,Lab Invest Med,LIM 25, BR-05403010 Sao Paulo, Brazil.
[Duarte, Yeda A. O.] Univ Sao Paulo, Sch Nursing, BR-05403010 Sao Paulo, Brazil.
[Lebrao, Maria Lucia] Univ Sao Paulo, Sch Publ Hlth, BR-05403010 Sao Paulo, Brazil.
[Naslavsky, Michel S.; Yamamoto, Guilherme L.; Lazar, Monize; Zatz, Mayana] Univ Sao Paulo, Human Genome Res Ctr, BR-05403010 Sao Paulo, Brazil.
[Cerutti, Janete M.] Univ Fed Sao Paulo, Dept Morphol & Genet, Div Genet, Genet Bases Thyroid Tumors Lab, Sao Paulo, Brazil.
[Lindsey, Susan C.; Camacho, Cleber P.; Maciel, Rui M. B.; Toledo, Sergio P. A.] Univ Fed Sao Paulo, Dept Med, Div Endocrinol, Lab Mol & Translat Endocrinol, Sao Paulo, Brazil.
[Sobreira, Tiago J. P.] Brazilian Natl Lab Biosci, Sao Paulo, Brazil.
[Garralda, Elena] Hosp Univ Sanchinarro, Ctr Integral Oncol Clara Campal, Madrid, Spain.
[Almeida, Marcio; Blangero, John] AT&T Genom Comp Ctr, Texas Biomed Res Inst, Dept Genet, San Antonio, TX USA.
[Lima, Jose V., Jr.] Santa Casa Hosp, Div Endocrinol, Sao Paulo, Brazil.
[Meirelles, Osorio] NIA, Lab Epidemiol & Populat Sci, Bethesda, MD 20892 USA.
RP Toledo, RA (reprint author), Univ Sao Paulo, Sch Med, Hosp Clin, Endocrine Genet Unit,Lab Invest Med,LIM 25, BR-05403010 Sao Paulo, Brazil.
EM toledorodrigo@usp.br
RI Lourenco , Delmar/B-8832-2012; Zatz, Mayana/M-5338-2015; Naslavsky,
Michel/L-1772-2015; Sobreira, Tiago/C-1276-2008; Lindsey,
Susan/N-2716-2014
OI Zatz, Mayana/0000-0003-3970-8025; Naslavsky, Michel/0000-0002-9068-1713;
Sobreira, Tiago/0000-0002-0217-0084;
FU Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)
[401.990/2010-9]; Fundacao de Amparo a Pesquisa do Estado de Sao Paulo
(FAPESP) [2013/01476-9, 2006/60402-1, 2010/51547-1]; Ciencias Sem
Fronteiras CNPq postdoctoral fellowship; FAPESP; Coordenadoria de
Aperfeicoamento de Pessoal de Nivel Superior (CAPES), Brazil [028/2013]
FX This study was supported by funds from the Conselho Nacional de
Desenvolvimento Cientifico e Tecnologico (CNPq), grant number
401.990/2010-9 and the Fundacao de Amparo a Pesquisa do Estado de Sao
Paulo (FAPESP) grants number 2013/01476-9 (to S P A Toledo) and
2006/60402-1 and 2010/51547-1 (to R M B Maciel). S P A Toledo, J M
Cerutti and R M B Maciel are investigators with the CNPq. R A Toledo has
received a Ciencias Sem Fronteiras CNPq postdoctoral fellowship and is
currently working at the Centro Nacional de Investigaciones Oncologicas
(CNIO) in Madrid. R Hatakana, T Sekiya, S C Lindsey, D M Lourenco Jr,
and R A Toledo received research fellowships from FAPESP. S P A Toledo
is a Senior Professor in the Division of Endocrinology, Department of
Medicine, Federal University of Sao Paulo, SP, Brazil, with a grant from
the Programa de Visitante Nacional Senior - Edital 028/2013 - from the
Coordenadoria de Aperfeicoamento de Pessoal de Nivel Superior (CAPES),
Brazil.
NR 42
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U1 1
U2 6
PU BIOSCIENTIFICA LTD
PI BRISTOL
PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT,
ENGLAND
SN 1351-0088
EI 1479-6821
J9 ENDOCR-RELAT CANCER
JI Endocr.-Relat. Cancer
PD FEB
PY 2015
VL 22
IS 1
BP 65
EP 76
DI 10.1530/ERC-14-0491
PG 12
WC Oncology; Endocrinology & Metabolism
SC Oncology; Endocrinology & Metabolism
GA CE7FD
UT WOS:000352002500015
PM 25425582
ER
PT J
AU Hoffman, K
Garantziotis, S
Birnbaum, LS
Stapleton, HM
AF Hoffman, Kate
Garantziotis, Stavros
Birnbaum, Linda S.
Stapleton, Heather M.
TI Monitoring Indoor Exposure to Organophosphate Flame Retardants: Hand
Wipes and House Dust
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Article
ID TRIS(1,3-DICHLORO-2-PROPYL) PHOSPHATE; URINARY METABOLITES; PHASE-OUT;
VARIABILITY; ZEBRAFISH; HANDWIPES; TDCPP; TRANSCRIPTIONS; ASSOCIATIONS;
DISPOSITION
AB BACKGROUND: Organophosphate flame retardants (PFRs) are becoming popular replacements for the phased-out polybrominated diphenyl ether (PBDE) mixtures, and they are now commonly detected in indoor environments. However, little is known about human exposure to PFRs because they cannot be easily measured in blood or serum.
OBJECTIVES: To investigate relationships between the home environment and internal exposure, we assessed associations between two PFRs, tris(1,3-dichloropropyl) phosphate (TDCIPP) and triphenyl phosphate (TPHP), in paired hand wipe and dust samples and concentrations of their metabolites in urine samples (n = 53). We also assessed short-term variation in urinary metabolite concentrations (n = 11 participants; n = 49 samples).
METHODS: Adult volunteers in North Carolina, USA, completed questionnaires and provided urine, hand wipe, and household dust samples. PFRs and PBDEs were measured in hand wipes and dust, and bis(1,3-dichloropropyl) phosphate (BDCIPP) and diphenyl phosphate (DPHP), metabolites of TDCIPP and TPHP, were measured in urine.
RESULTS: TDCIPP and TPHP were detected frequently in hand wipes and dust (> 86.8%), with geometric mean concentrations exceeding those of PBDEs. Unlike PBDEs, dust TDCIPP and TPHP levels were not associated with hand wipes. However, hand wipe levels were associated with urinary metabolites. Participants with the highest hand wipe TPHP mass, for instance, had DPHP levels 2.42 times those of participants with the lowest levels (95% CI: 1.23, 4.77). Women had higher levels of DPHP, but not BDCIPP. BDCIPP and DPHP concentrations were moderately to strongly reliable over 5 consecutive days (intra-class correlation coefficients of 0.81 and 0.51, respectively).
CONCLUSIONS: PFR exposures are widespread, and hand-to-mouth contact or dermal absorption may be important pathways of exposure.
C1 [Hoffman, Kate; Stapleton, Heather M.] Duke Univ, Nicholas Sch Environm, Durham, NC 27708 USA.
[Garantziotis, Stavros] NIEHS, NIH, DHHS, Res Triangle Pk, NC 27709 USA.
[Birnbaum, Linda S.] NCI, NIH, DHHS, Res Triangle Pk, NC USA.
RP Stapleton, HM (reprint author), Duke Univ, Nicholas Sch Environm, A220 LSRC Box 90328, Durham, NC 27708 USA.
EM heather.stapleton@duke.edu
RI Garantziotis, Stavros/A-6903-2009
OI Garantziotis, Stavros/0000-0003-4007-375X
FU National Institute of Environmental Health Sciences (NIEHS) [R01
ES016099]; intramural programs of the NIEHS; National Institutes of
Health; National Cancer Institute
FX This study was supported by a research grant to H.M.S. from the National
Institute of Environmental Health Sciences (NIEHS; R01 ES016099) and by
the intramural programs of the NIEHS, the National Institutes of Health,
and the National Cancer Institute. K.H. was supported through a donation
provided by Fred and Alice Stanback.
NR 37
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Z9 24
U1 16
U2 156
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 FEB
PY 2015
VL 123
IS 2
BP 160
EP 165
DI 10.1289/ehp.1408669
PG 6
WC Environmental Sciences; Public, Environmental & Occupational Health;
Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Toxicology
GA CE8GI
UT WOS:000352079400016
PM 25343780
ER
PT J
AU Rogalsky, DK
Mendola, P
Metts, TA
Martin, WJ
AF Rogalsky, Derek K.
Mendola, Pauline
Metts, Tricia A.
Martin, William J., II
TI Estimating the Number of Vulnerable People in the United States Exposed
to Residential Wood Smoke: Rogalsky et al. Respond
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Letter
C1 [Rogalsky, Derek K.] Georgetown Univ, Sch Med, Washington, DC 20057 USA.
[Mendola, Pauline; Martin, William J., II] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Dept Hlth & Human Serv, Bethesda, MD USA.
[Metts, Tricia A.] E Tennessee State Univ, Dept Environm Hlth, Johnson City, TN 37614 USA.
RP Rogalsky, DK (reprint author), Georgetown Univ, Sch Med, Washington, DC 20057 USA.
EM dkr24@georgetown.edu
OI Mendola, Pauline/0000-0001-5330-2844
NR 4
TC 0
Z9 0
U1 1
U2 1
PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE
PI RES TRIANGLE PK
PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233,
RES TRIANGLE PK, NC 27709-2233 USA
SN 0091-6765
EI 1552-9924
J9 ENVIRON HEALTH PERSP
JI Environ. Health Perspect.
PD FEB
PY 2015
VL 123
IS 2
BP A30
EP A31
DI 10.1289/ehp.1409136R
PG 2
WC Environmental Sciences; Public, Environmental & Occupational Health;
Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Toxicology
GA CE8GI
UT WOS:000352079400002
PM 25642727
ER
PT J
AU Krzak, JJ
Corcos, DM
Damiano, DL
Graf, A
Hedeker, D
Smith, PA
Harris, GF
AF Krzak, Joseph J.
Corcos, Daniel M.
Damiano, Diane L.
Graf, Adam
Hedeker, Donald
Smith, Peter A.
Harris, Gerald F.
TI Kinematic foot types in youth with equinovarus secondary to hemiplegia
SO GAIT & POSTURE
LA English
DT Article
DE Cerebral palsy; Equinovarus; Gait; Multi-segmental foot modeling
ID POSTERIOR TIBIAL TENDON; CEREBRAL-PALSY; GAIT PATTERNS; SPASTIC
HEMIPLEGIA; CHILDREN; DEFORMITY; ANTERIOR; SURGERY
AB Background: Elevated kinematic variability of the foot and ankle segments exists during gait among individuals with equinovarus secondary to hemiplegic cerebral palsy (CP). Clinicians have previously addressed such variability by developing classification schemes to identify subgroups of individuals based on their kinematics.
Objective: To identify kinematic subgroups among youth with equinovarus secondary to CP using 3-dimensional multi-segment foot and ankle kinematics during locomotion as inputs for principal component analysis (PCA), and K-means cluster analysis.
Methods: In a single assessment session, multi-segment foot and ankle kinematics using the Milwaukee Foot Model (MFM) were collected in 24 children/adolescents with equinovarus and 20 typically developing children/adolescents.
Results: PCA was used as a data reduction technique on 40 variables. K-means cluster analysis was performed on the first six principal components (PCs) which accounted for 92% of the variance of the dataset. The PCs described the location and plane of involvement in the foot and ankle. Five distinct kinematic subgroups were identified using K-means clustering. Participants with equinovarus presented with variable involvement ranging from primary hindfoot or forefoot deviations to deformtiy that included both segments in multiple planes.
Conclusion: This study provides further evidence of the variability in foot characteristics associated with equinovarus secondary to hemiplegic CP. These findings would not have been detected using a single segment foot model. The identification of multiple kinematic subgroups with unique foot and ankle characteristics has the potential to improve treatment since similar patients within a subgroup are likely to benefit from the same intervention(s). (C) 2014 Elsevier B.V. All rights reserved.
C1 [Krzak, Joseph J.] Midwestern Univ, Coll Hlth Sci, Phys Therapy Program, Downers Grove, IL 60515 USA.
[Krzak, Joseph J.; Graf, Adam; Smith, Peter A.; Harris, Gerald F.] Shriners Hosp Children Chicago, Chicago, IL USA.
[Corcos, Daniel M.] Northwestern Univ, Dept Phys Therapy & Human Movement Sci, Feinberg Sch Med, Chicago, IL 60611 USA.
[Damiano, Diane L.] NIH, Funct & Appl Biomech Sect, Bethesda, MD 20892 USA.
[Hedeker, Donald] Univ Chicago, Dept Publ Hlth Sci, Chicago, IL 60637 USA.
[Smith, Peter A.] Rush Univ, Med Ctr, Dept Orthopaed Surg, Coll Med, Chicago, IL 60612 USA.
[Harris, Gerald F.] Marquette Univ, Med Coll Wisconsin, Orthopaed & Rehabil Engn Ctr, Milwaukee, WI 53233 USA.
RP Krzak, JJ (reprint author), Midwestern Univ, Coll Hlth Sci, Phys Therapy Program, 555 31st St, Downers Grove, IL 60515 USA.
EM joekrzak@sbcglobal.net
RI Damiano, Diane/B-3338-2010
OI Damiano, Diane/0000-0002-2770-5356
FU Intramural Research Program of the NIH Clinical Center
FX The authors would like to thank Ms. Kathryn Reiners for her assistance
with data collection, as well as, the children and familes who gave
their time to participate in this project. This work was supported in
part by the Intramural Research Program of the NIH Clinical Center.
NR 33
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U1 0
U2 6
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0966-6362
EI 1879-2219
J9 GAIT POSTURE
JI Gait Posture
PD FEB
PY 2015
VL 41
IS 2
BP 402
EP 408
DI 10.1016/j.gaitpost.2014.10.027
PG 7
WC Neurosciences; Orthopedics; Sport Sciences
SC Neurosciences & Neurology; Orthopedics; Sport Sciences
GA CE6GC
UT WOS:000351933700009
PM 25467429
ER
PT J
AU Besharat, S
Poustchi, H
Mohamadkhani, A
Katoonizadeh, A
Moradi, A
Roshandel, G
Freedman, ND
Malekzadeh, R
AF Besharat, Sima
Poustchi, Hossein
Mohamadkhani, Ashraf
Katoonizadeh, Aezam
Moradi, Abdolvahab
Roshandel, Gholamreza
Freedman, Neal David
Malekzadeh, Reza
TI Association of Mutations in the Basal Core Promoter and Pre-core Regions
of the Hepatitis B Viral Genome and Longitudinal Changes in HBV Level in
HBeAg Negative Individuals: Results From a Cohort Study in Northern Iran
SO HEPATITIS MONTHLY
LA English
DT Article
DE Hepatitis B; Chronic; Mutation; Genome; Viral
ID HEPATOCELLULAR-CARCINOMA; SURFACE-ANTIGEN; ESOPHAGEAL CANCER; VIRUS
INFECTION; GENOTYPE; MUTANTS; REPLICATION; FREQUENCY; PROVINCE; THERAPY
AB Background: Although certain HBV mutations are known to affect the expression of Hepatitis e antigen, their association with HBV viral level or clinical outcomes is less clear.
Objectives: We evaluated associations between different mutations in the Basal Core promoter (BCP) and Pre-core (PC) regions of HBV genome and subsequent changes in HBV viral DNA level over seven years in a population of untreated HBeAg negative chronic hepatitis B (CHB) participants in Northeast of Iran.
Materials and Methods: Participants in the current study were drawn from the Golestan Hepatitis B Cohort Study (GHBCS), a cohort of approximately 2590 HBsAg positive subjects (living in Gonbad city) embedded in the Golestan Cohort Study (GCS). At baseline, HBsAg was measured in all participants and revealed 2590 HBsAg positive cases. We randomly selected 304 participants who their blood sample were taken at both baseline and seven years later in follow-up and had not been treated for HBV during this time. HBV viral load were assessed at baseline and at year 7. The BCP and PC regions of the HBV DNA, at baseline, were amplified via hemi-nested PCR and sequenced by cycle sequencing. At year 7, liver stiffness was assessed by fibroscan; also, other parameters of liver disease were assessed following standard clinical protocols. Associations were assessed via tabulation, chi-square, t-tests and logistic regression. P values < 0.05 were considered statistically significant and all tests were two-sided.
Results: Among 304 HBsAg positive participants, 99 had detectable HBV DNA at study baseline. Of these, 61.6% had PC mutations (48.5% A1896 and 25.2% G1899). In contrast to other mutations, A1896 was associated with a higher proportion of detectable HBV DNA at year 7 (39.6%) compared to patients with the wild type (13.7%) (OR: 4.36, CI95% = 1.63-11.70; P Value = 0.002). Although participants with the A1896 mutation had higher year-7 HBV viral load than participants with G1896 (2.30 +/- 1.66 IU/mL vs. 1.76 +/- 1 IU/mL among patients with detectable HBV; P value = 0.052), no association was observed with either serum level ALT or liver stiffness. Interestingly, mutations in the basal core promoter (BCP) region had no significant effect on virus DNA detection.
Conclusions: In this population with chronic HBeAg negative hepatitis B, an association was observed between the G1896A mutation in the Pre-core region of HBV and subsequent level of HBV DNA seven years later, which indicated that mutations in this region of HBV genome may contribute to disease progression in these patients and play an important role in HBV natural course of disease.
C1 [Besharat, Sima; Poustchi, Hossein; Mohamadkhani, Ashraf; Katoonizadeh, Aezam; Roshandel, Gholamreza; Malekzadeh, Reza] Univ Tehran Med Sci, Digest Dis Res Inst, Liver & Pancreatobiliary Dis Res Ctr, Tehran, Iran.
[Besharat, Sima; Moradi, Abdolvahab; Roshandel, Gholamreza] Golestan Univ Med Sci, Golestan Res Ctr Gastroentrol & Hepatol, Gorgan, Iran.
[Freedman, Neal David] NCI, Div Canc Epidemiol & Genet, NIH, US Dept HHS, Rockville, MD USA.
RP Poustchi, H (reprint author), Univ Tehran Med Sci, Digest Dis Res Inst, Liver & Pancreatobiliary Dis Res Ctr, Shariati Hosp, North Kargar Ave,POB 14117-13135, Tehran, Iran.
EM h.poustchi@gmail.com
RI Freedman, Neal/B-9741-2015; Besharat, Sima/L-7351-2016; Roshandel,
gholamreza/N-2260-2016; Moradi, Abdolvahab/C-1680-2017
OI Freedman, Neal/0000-0003-0074-1098; Besharat, Sima/0000-0002-0540-6056;
Roshandel, gholamreza/0000-0002-5494-0722; Moradi,
Abdolvahab/0000-0003-2877-4190
FU Tehran University of Medical Sciences (TUMS), Research Deputy
FX This paper is in partial fulfillment of a doctoral thesis in cellular
and molecular research. Authors give thanks for the financial support of
Tehran University of Medical Sciences (TUMS), Research Deputy. Special
thanks are given to the staff of Digestive Diseases Research Institute
(DDRI), laboratory division.
NR 31
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U1 3
U2 5
PU KOWSAR PUBL
PI HOENSBROEK
PA PATERSWEG 22,, HOENSBROEK, LIMBURG 6431 GC, NETHERLANDS
SN 1735-143X
EI 1735-3408
J9 HEPAT MON
JI Hepat. Mon.
PD FEB
PY 2015
VL 15
IS 2
AR e23875
DI 10.5812/hepatmon.23875
PG 6
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA CE3IG
UT WOS:000351719300004
PM 25788956
ER
PT J
AU Roukos, V
Pegoraro, G
Voss, TC
Misteli, T
AF Roukos, Vassilis
Pegoraro, Gianluca
Voss, Ty C.
Misteli, Tom
TI Cell cycle staging of individual cells by fluorescence microscopy
SO NATURE PROTOCOLS
LA English
DT Article
ID LASER-SCANNING CYTOMETRY; DNA-REPLICATION; LIVING CELLS; FLOW-CYTOMETRY;
DYNAMICS; CANCER; PROLIFERATION; CHROMATIN; ANTIBODY; MITOSIS
AB Progression through the cell cycle is one of the most fundamental features of cells. Studies of the cell cycle have traditionally relied on the analysis of populations, and they often require specific markers or the use of genetically modified systems, making it difficult to determine the cell cycle stage of individual, unperturbed cells. We describe a protocol, suitable for use in high-resolution imaging approaches, for determining cell cycle staging of individual cells by measuring their DNA content by fluorescence microscopy. The approach is based on the accurate quantification by image analysis of the integrated nuclear intensity of cells stained with a DNA dye, and it can be used in combination with several histochemical methods. We describe and provide the algorithms for two automated image analysis pipelines and the derivation of cell cycle profiles with both commercial and open-source software. This 1-2-d protocol is applicable to adherent cells, and it is adaptable for use with several DNA dyes.
C1 [Roukos, Vassilis; Pegoraro, Gianluca; Voss, Ty C.; Misteli, Tom] NCI, NIH, Bethesda, MD 20892 USA.
[Pegoraro, Gianluca] NCI, High Throughput Imaging Facil, NIH, Bethesda, MD 20892 USA.
[Voss, Ty C.] PerkinElmer Hlth Sci Inc, Waltham, MD USA.
RP Roukos, V (reprint author), NCI, NIH, Bethesda, MD 20892 USA.
EM roukosv@mail.nih.gov; mistelit@mail.nih.gov
OI Pegoraro, Gianluca/0000-0003-2843-9464
FU Intramural Research Program of the US National Institutes of Health
(NIH); Intramural Research Program of the US National Institutes of
Health (NIH), National Cancer Institute (NCI), Center for Cancer
Research
FX Work in the Misteli laboratory and in the High-Throughput Imaging
Facility is supported by the Intramural Research Program of the US
National Institutes of Health (NIH), National Cancer Institute (NCI),
Center for Cancer Research. We thank S. Burke for modeling the cell
cycle data, K. MacKinnon for help with flow cytometry and T. Karpova
(NCI Fluorescence Imaging Facility) for help with microscopy.
NR 51
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U1 2
U2 20
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1754-2189
EI 1750-2799
J9 NAT PROTOC
JI Nat. Protoc.
PD FEB
PY 2015
VL 10
IS 2
BP 334
EP 348
DI 10.1038/nprot.2015.016
PG 15
WC Biochemical Research Methods
SC Biochemistry & Molecular Biology
GA CE6ET
UT WOS:000351930100008
PM 25633629
ER
PT J
AU Alewine, C
Hassan, R
Pastan, I
AF Alewine, Christine
Hassan, Raffit
Pastan, Ira
TI Advances in Anticancer Immunotoxin Therapy
SO ONCOLOGIST
LA English
DT Article
DE Antibody conjugate; Recombinant immunotoxin; Vascular leak syndrome;
Antidrug antibody
ID VASCULAR LEAK SYNDROME; NON-HODGKINS-LYMPHOMA; T-CELL LYMPHOMA; PHASE-I
TRIAL; TRIPLE-NEGATIVE BREAST; MALIGNANT BRAIN-TUMORS; RECOMBINANT
IMMUNOTOXIN; ANTIBODY-RICIN; CHAIN IMMUNOCONJUGATE; DENILEUKIN DIFTITOX
AB Immunotoxins are a novel class of antibody-conjugated therapeutics currently in clinical development for a variety of malignancies. They consist of an antibody-based targeting domain fused to a bacterial toxin payload for cell killing. Immunotoxins kill cellsbyinhibiting protein synthesis, aunique mechanism of action that is toxic to both dividing and nondividing cells. Recent advances in the design and administration of immunotoxins are overcoming historical challenges in the field, leading torenewedinterest in these therapeutics.
C1 [Alewine, Christine; Pastan, Ira] NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
[Hassan, Raffit] NCI, Thorac & Gastrointestinal Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Pastan, I (reprint author), NCI, Mol Biol Lab, 37 Convent Dr,Room 5106, Bethesda, MD 20892 USA.
EM pastani@mail.nih.gov
FU Intramural Research Program of the NIH, National Cancer Institute, and
Center for Cancer Research
FX This research was supported by the Intramural Research Program of the
NIH, National Cancer Institute, and Center for Cancer Research.
NR 82
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U1 2
U2 8
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 FEB
PY 2015
VL 20
IS 2
BP 176
EP 185
DI 10.1634/theoncologist.2014-0358
PG 10
WC Oncology
SC Oncology
GA CE5ZR
UT WOS:000351915500014
PM 25561510
ER
PT J
AU Nass, SJ
Beaupin, LK
Demark-Wahnefried, W
Fasciano, K
Ganz, PA
Hayes-Lattin, B
Hudson, MM
Nevidjon, B
Oeffinger, KC
Rechis, R
Richardson, LC
Seibel, NL
Smith, AW
AF Nass, Sharyl J.
Beaupin, Lynda K.
Demark-Wahnefried, Wendy
Fasciano, Karen
Ganz, Patricia A.
Hayes-Lattin, Brandon
Hudson, Melissa M.
Nevidjon, Brenda
Oeffinger, Kevin C.
Rechis, Ruth
Richardson, Lisa C.
Seibel, Nita L.
Smith, Ashley W.
TI Identifying and Addressing theNeeds of Adolescents and Young Adults With
Cancer: Summary of an Institute of Medicine Workshop
SO ONCOLOGIST
LA English
DT Article
DE Adolescent; Young adult; Cancer survivorship; Psychosocial aspects;
Fertility preservation; Adverse effects
ID LONG-TERM SURVIVORS; ACUTE LYMPHOBLASTIC-LEUKEMIA; HEALTH-INSURANCE
COVERAGE; CAUSE-SPECIFIC MORTALITY; CHILDHOOD-CANCER; BREAST-CANCER;
FERTILITY PRESERVATION; HODGKIN LYMPHOMA; PALLIATIVE CARE;
PHYSICAL-ACTIVITY
AB Cancer is the leading disease-related cause of death in adolescents and young adults (AYAs). This population faces many short-and long-term health and psychosocial consequences of cancer diagnosis and treatment, but many programs for cancer treatment, survivorship care, and psychosocial support do not focus on the specific needs of AYA cancer patients. Recognizing this health care disparity, the National Cancer Policy Forum of the Institute of Medicine convened a public workshop to examine the needs of AYA patients with cancer. Workshop participants identified many gaps and challenges in the care of AYA cancer patients and discussed potential strategies to address these needs. Suggestions included ways to improve access to care for AYAs, to deliver cancer care that better meets the medical and psychosocial needs of AYAs, to develop educational programs for providers who care for AYA cancer survivors, and to enhance the evidence base for AYAs with cancer by facilitating participation in research.
C1 [Nass, Sharyl J.] Inst Med, Washington, DC 20001 USA.
[Beaupin, Lynda K.] Roswell Pk Canc Inst, Buffalo, NY 14263 USA.
[Demark-Wahnefried, Wendy] Univ Alabama Birmingham, Birmingham Comprehens Canc Ctr, Birmingham, AL USA.
[Fasciano, Karen] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
[Ganz, Patricia A.] Univ Calif Los Angeles, Sch Med & Publ Hlth, Los Angeles, CA USA.
[Hayes-Lattin, Brandon] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA.
[Hudson, Melissa M.] St Jude Childrens Res Hosp, Memphis, TN 38105 USA.
[Nevidjon, Brenda] Oncol Nursing Soc, Pittsburgh, PA USA.
[Oeffinger, Kevin C.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
[Rechis, Ruth] LIVESTRONG Fdn, Austin, TX USA.
[Richardson, Lisa C.] Ctr Dis Control & Prevent, Atlanta, GA USA.
[Seibel, Nita L.; Smith, Ashley W.] Natl Canc Inst, Bethesda, MD USA.
RP Nass, SJ (reprint author), Inst Med, Natl Canc Policy Forum, 500 Fifth St, Washington, DC 20001 USA.
EM snass@nas.edu
FU LIVESTRONG Foundation; Young Adult Cancer Alliance; IOM's National
Cancer Policy Forum
FX The responsibility for the content of this article rests with the
authors and does not necessarily represent the views of the Institute of
Medicine, its committees, its sponsors, or its convening activities and
does not represent the official position of the Centers for Disease
Control and Prevention or that of the National Cancer Institute. We
thank the LIVESTRONG Foundation for generously cosponsoring the IOM
workshop and Critical Mass: The Young Adult Cancer Alliance for
supporting the workshop. The activities of the IOM's National Cancer
Policy Forum are supported by its sponsoring members, which currently
include the Centers for Disease Control and Prevention, the National
Cancer Institute, the Association of American Cancer Institutes, the
American Association for Cancer Research, the American Cancer Society,
the American Society of Clinical Oncology, the American Society of
Hematology, the American Society for Radiation Oncology, AstraZeneca,
Bristol-Myers Squibb, C-Change, the Cancer Support Community, the CEO
Roundtable on Cancer, EMD Serono, Helsinn Group, the LIVESTRONG
Foundation, the National Comprehensive Cancer Network, Novartis
Oncology, the Oncology Nursing Society, and Sanofi Oncology. We thank
the speakers and participants for their contributions to the workshop.
We also thank Sarah Bender and Sara Tharakan for assistance with
manuscript preparation.
NR 89
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U2 10
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 FEB
PY 2015
VL 20
IS 2
BP 186
EP 195
DI 10.1634/theoncologist.2014-0265
PG 10
WC Oncology
SC Oncology
GA CE5ZR
UT WOS:000351915500015
PM 25568146
ER
PT J
AU Zheng, M
Zhang, HL
Dill, DL
Clark, JD
Tu, SS
Yablonovitch, AL
Tan, MH
Zhang, R
Rujescu, D
Wu, MH
Tessarollo, L
Vieira, W
Gottesman, MM
Deng, SH
Eberlin, LS
Zare, RN
Billard, JM
Gillet, JP
Li, JB
Peltz, G
AF Zheng, Ming
Zhang, Haili
Dill, David L.
Clark, J. David
Tu, Susan
Yablonovitch, Arielle L.
Tan, Meng How
Zhang, Rui
Rujescu, Dan
Wu, Manhong
Tessarollo, Lino
Vieira, Wilfred
Gottesman, Michael M.
Deng, Suhua
Eberlin, Livia S.
Zare, Richard N.
Billard, Jean-Martin
Gillet, Jean-Pierre
Li, Jin Billy
Peltz, Gary
TI The Role of Abcb5 Alleles in Susceptibility to Haloperidol-Induced
Toxicity in Mice and Humans
SO PLOS MEDICINE
LA English
DT Article
ID BLOOD-BRAIN-BARRIER; PYRIDINIUM METABOLITE; TARDIVE-DYSKINESIA;
NEUROTOXIN; PARKINSONISM; MITOCHONDRIA; ASSOCIATION; DISCOVERY;
TRANSPORT; PHARMACOGENOMICS
AB Background
We know very little about the genetic factors affecting susceptibility to drug-induced central nervous system (CNS) toxicities, and this has limited our ability to optimally utilize existing drugs or to develop new drugs for CNS disorders. For example, haloperidol is a potent dopamine antagonist that is used to treat psychotic disorders, but 50% of treated patients develop characteristic extrapyramidal symptoms caused by haloperidol-induced toxicity (HIT), which limits its clinical utility. We do not have any information about the genetic factors affecting this drug-induced toxicity. HIT in humans is directly mirrored in a murine genetic model, where inbred mouse strains are differentially susceptible to HIT. Therefore, we genetically analyzed this murine model and performed a translational human genetic association study.
Methods and Findings
A whole genome SNP database and computational genetic mapping were used to analyze the murine genetic model of HIT. Guided by the mouse genetic analysis, we demonstrate that genetic variation within an ABC-drug efflux transporter (Abcb5) affected susceptibility to HIT. In situ hybridization results reveal that Abcb5 is expressed in brain capillaries, and by cerebellar Purkinje cells. We also analyzed chromosome substitution strains, imaged haloperidol abundance in brain tissue sections and directly measured haloperidol (and its metabolite) levels in brain, and characterized Abcb5 knockout mice. Our results demonstrate that Abcb5 is part of the blood-brain barrier; it affects susceptibility to HIT by altering the brain concentration of haloperidol. Moreover, a genetic association study in a haloperidol-treated human cohort indicates that human ABCB5 alleles had a time-dependent effect on susceptibility to individual and combined measures of HIT. Abcb5 alleles are pharmacogenetic factors that affect susceptibility to HIT, but it is likely that additional pharmacogenetic susceptibility factors will be discovered.
Conclusions
ABCB5 alleles alter susceptibility to HIT in mouse and humans. This discovery leads to a new model that (at least in part) explains inter-individual differences in susceptibility to a drug-induced CNS toxicity.
C1 [Zheng, Ming; Zhang, Haili; Wu, Manhong; Peltz, Gary] Stanford Univ, Sch Med, Dept Anesthesia, Stanford, CA 94305 USA.
[Dill, David L.; Tu, Susan] Stanford Univ, Comp Sci, Stanford, CA 94305 USA.
[Clark, J. David] Vet Affairs Palo Alto Hlth Care Syst, Palo Alto, CA USA.
[Yablonovitch, Arielle L.; Tan, Meng How; Zhang, Rui; Li, Jin Billy] Stanford Univ, Sch Med, Dept Genet, Stanford, CA 94305 USA.
[Rujescu, Dan] Univ Halle, Dept Psychiat, Halle, Germany.
[Tessarollo, Lino] NCI, Ctr Canc Res, Frederick, MD 21701 USA.
[Vieira, Wilfred; Gottesman, Michael M.] NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA.
[Deng, Suhua] Stanford Univ, Sch Med, Dept Pathol, Stanford, CA 94305 USA.
[Eberlin, Livia S.; Zare, Richard N.] Stanford Univ, Dept Chem, Stanford, CA 94305 USA.
[Billard, Jean-Martin; Gillet, Jean-Pierre] Univ Namur, Lab Mol Canc Biol, Mol Physiol Res Unit URPhyM, Namur Res Inst Life Sci NARILIS, Namur, Belgium.
RP Zheng, M (reprint author), Stanford Univ, Sch Med, Dept Anesthesia, Stanford, CA 94305 USA.
EM jin.billy.li@stanford.edu; gpeltz@stanford.edu
RI Tan, Meng How/M-8605-2015
FU King Abdullah University of Science and Technology (KAUST) under KAUST
Stanford Academic Excellence Alliance program [1R01DK090992-01];
Stanford's CURIS program; Center for Molecular Analysis and Design
(CMAD)
FX GP and MZ were partially supported by funding from a transformative RO1
award (1R01DK090992-01) DLD was supported by a King Abdullah University
of Science and Technology (KAUST) research grant under the KAUST
Stanford Academic Excellence Alliance program. ST was supported by
Stanford's CURIS program for summer research interns. LSE was supported
by a postdoctoral fellowship from the Center for Molecular Analysis and
Design (CMAD). The funders had no role in study design, data collection
and analysis, decision to publish, or preparation of the manuscript.
NR 57
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PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1549-1676
J9 PLOS MED
JI PLos Med.
PD FEB
PY 2015
VL 12
IS 2
AR UNSP e1001782
DI 10.1371/journal.pmed.1001782
PG 29
WC Medicine, General & Internal
SC General & Internal Medicine
GA CE3GY
UT WOS:000351715900001
PM 25647612
ER
PT J
AU Sullivan, DC
Bresolin, L
Seto, B
Obuchowski, NA
Raunig, DL
Kessler, LG
AF Sullivan, Daniel C.
Bresolin, Linda
Seto, Belinda
Obuchowski, Nancy A.
Raunig, David L.
Kessler, Larry G.
TI Introduction to metrology series
SO STATISTICAL METHODS IN MEDICAL RESEARCH
LA English
DT Editorial Material
C1 [Sullivan, Daniel C.] Duke Univ, Med Ctr, Dept Radiol, Durham, NC 27710 USA.
[Bresolin, Linda] RSNA, Oak Brook, IL USA.
[Seto, Belinda] NEI, NIH, Bethesda, MD 20892 USA.
[Obuchowski, Nancy A.] Cleveland Clin, Quantitat Hlth Sci, Cleveland, OH 44106 USA.
[Raunig, David L.] ICON Med Imaging, Warrington, Cheshire, England.
[Kessler, Larry G.] Univ Washington, Dept Hlth Serv, Sch Publ Hlth, Seattle, WA 98195 USA.
RP Sullivan, DC (reprint author), Duke Univ, Med Ctr, Dept Radiol, Box 3302, Durham, NC 27710 USA.
EM daniel.sullivan@duke.edu
NR 5
TC 3
Z9 3
U1 1
U2 5
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 0962-2802
EI 1477-0334
J9 STAT METHODS MED RES
JI Stat. Methods Med. Res.
PD FEB
PY 2015
VL 24
IS 1
SI SI
BP 3
EP 8
DI 10.1177/0962280214537332
PG 6
WC Health Care Sciences & Services; Mathematical & Computational Biology;
Medical Informatics; Statistics & Probability
SC Health Care Sciences & Services; Mathematical & Computational Biology;
Medical Informatics; Mathematics
GA CE4ZZ
UT WOS:000351840700001
PM 25804285
ER
PT J
AU Raunig, DL
McShane, LM
Pennello, G
Gatsonis, C
Carson, PL
Voyvodic, JT
Wahl, RL
Kurland, BF
Schwarz, AJ
Gonen, M
Zahlmann, G
Kondratovich, MV
O'Donnell, K
Petrick, N
Cole, PE
Garra, B
Sullivan, DC
AF Raunig, David L.
McShane, Lisa M.
Pennello, Gene
Gatsonis, Constantine
Carson, Paul L.
Voyvodic, James T.
Wahl, Richard L.
Kurland, Brenda F.
Schwarz, Adam J.
Goenen, Mithat
Zahlmann, Gudrun
Kondratovich, Marina V.
O'Donnell, Kevin
Petrick, Nicholas
Cole, Patricia E.
Garra, Brian
Sullivan, Daniel C.
CA QIBA Tech Performance Working Grp
TI Quantitative imaging biomarkers: A review of statistical methods for
technical performance assessment
SO STATISTICAL METHODS IN MEDICAL RESEARCH
LA English
DT Article
DE quantitative imaging; imaging biomarkers; reliability; linearity; bias;
precision; repeatability; reproducibility; agreement
ID CONFIDENCE-INTERVALS; ASSESSING AGREEMENT; RELIABILITY; DEFINITIONS;
COEFFICIENT; MEDICINE; POINTS
AB Technological developments and greater rigor in the quantitative measurement of biological features in medical images have given rise to an increased interest in using quantitative imaging biomarkers to measure changes in these features. Critical to the performance of a quantitative imaging biomarker in preclinical or clinical settings are three primary metrology areas of interest: measurement linearity and bias, repeatability, and the ability to consistently reproduce equivalent results when conditions change, as would be expected in any clinical trial. Unfortunately, performance studies to date differ greatly in designs, analysis method, and metrics used to assess a quantitative imaging biomarker for clinical use. It is therefore difficult or not possible to integrate results from different studies or to use reported results to design studies. The Radiological Society of North America and the Quantitative Imaging Biomarker Alliance with technical, radiological, and statistical experts developed a set of technical performance analysis methods, metrics, and study designs that provide terminology, metrics, and methods consistent with widely accepted metrological standards. This document provides a consistent framework for the conduct and evaluation of quantitative imaging biomarker performance studies so that results from multiple studies can be compared, contrasted, or combined.
C1 [Raunig, David L.] ICON Med Imaging, Warrington, PA 18976 USA.
[McShane, Lisa M.] NCI, Bethesda, MD 20892 USA.
[Pennello, Gene; Kondratovich, Marina V.; Petrick, Nicholas; Garra, Brian] US FDA, CDRH, Silver Spring, MD USA.
[Gatsonis, Constantine] Brown Univ, Providence, RI 02912 USA.
[Carson, Paul L.] Univ Michigan Hlth Syst, Ann Arbor, MI USA.
[Voyvodic, James T.] Duke Univ BIAC, Durham, NC USA.
[Wahl, Richard L.] Johns Hopkins Med Inst, Baltimore, MD 21205 USA.
[Kurland, Brenda F.] Univ Pittsburgh, Pittsburgh, PA USA.
[Schwarz, Adam J.] Eli Lilly & Co, Indianapolis, IN 46285 USA.
[Goenen, Mithat] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
[Zahlmann, Gudrun] Hoffman La Roche Ltd, Basel, Switzerland.
[O'Donnell, Kevin] Toshiba Med Res Inst, Vernon Hills, IL USA.
[Cole, Patricia E.] Takaeda, Deerfield, IL USA.
[Sullivan, Daniel C.] Duke Univ, Sch Med, Durham, NC 27706 USA.
RP Raunig, DL (reprint author), ICON Med Imaging, 2800 Kelly Rd, Warrington, PA 18976 USA.
EM David.Raunig@iconplc.com
OI Kurland, Brenda/0000-0002-5669-0595
FU Radiological Society of North America; NIH/NIBIB [HHSN268201000050C]
FX The authors acknowledge and appreciate the Radiological Society of North
America and NIH/NIBIB contract #HHSN268201000050C for supporting two
workshops and numerous conference calls for the authors' Working Group.
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PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 0962-2802
EI 1477-0334
J9 STAT METHODS MED RES
JI Stat. Methods Med. Res.
PD FEB
PY 2015
VL 24
IS 1
SI SI
BP 27
EP 67
DI 10.1177/0962280214537344
PG 41
WC Health Care Sciences & Services; Mathematical & Computational Biology;
Medical Informatics; Statistics & Probability
SC Health Care Sciences & Services; Mathematical & Computational Biology;
Medical Informatics; Mathematics
GA CE4ZZ
UT WOS:000351840700003
PM 24919831
ER
PT J
AU Obuchowski, NA
Reeves, AP
Huang, EP
Wang, XF
Buckler, AJ
Kim, HJ
Barnhart, HX
Jackson, EF
Giger, ML
Pennello, G
Toledano, AY
Kalpathy-Cramer, J
Apanasovich, TV
Kinahan, PE
Myers, KJ
Goldgof, DB
Barboriak, DP
Gillies, RJ
Schwartz, LH
Sullivan, DC
AF Obuchowski, Nancy A.
Reeves, Anthony P.
Huang, Erich P.
Wang, Xiao-Feng
Buckler, Andrew J.
Kim, Hyun J. (Grace)
Barnhart, Huiman X.
Jackson, Edward F.
Giger, Maryellen L.
Pennello, Gene
Toledano, Alicia Y.
Kalpathy-Cramer, Jayashree
Apanasovich, Tatiyana V.
Kinahan, Paul E.
Myers, Kyle J.
Goldgof, Dmitry B.
Barboriak, Daniel P.
Gillies, Robert J.
Schwartz, Lawrence H.
Sullivan, Daniel C.
CA Algorithm Comparison Working Grp
TI Quantitative imaging biomarkers: A review of statistical methods for
computer algorithm comparisons
SO STATISTICAL METHODS IN MEDICAL RESEARCH
LA English
DT Article
DE quantitative imaging; imaging biomarkers; image metrics; bias;
precision; repeatability; reproducibility; agreement
ID ASSESSING AGREEMENT; GOLD STANDARD; LUNG-CANCER; EVALUATE
REPRODUCIBILITY; CONCORDANCE CORRELATION; REGRESSION PROCEDURES;
INDIVIDUAL AGREEMENT; MALIGNANT-TUMORS; EM ALGORITHM; FDG-PET
AB Quantitative biomarkers from medical images are becoming important tools for clinical diagnosis, staging, monitoring, treatment planning, and development of new therapies. While there is a rich history of the development of quantitative imaging biomarker (QIB) techniques, little attention has been paid to the validation and comparison of the computer algorithms that implement the QIB measurements. In this paper we provide a framework for QIB algorithm comparisons. We first review and compare various study designs, including designs with the true value (e.g. phantoms, digital reference images, and zero-change studies), designs with a reference standard (e.g. studies testing equivalence with a reference standard), and designs without a reference standard (e.g. agreement studies and studies of algorithm precision). The statistical methods for comparing QIB algorithms are then presented for various study types using both aggregate and disaggregate approaches. We propose a series of steps for establishing the performance of a QIB algorithm, identify limitations in the current statistical literature, and suggest future directions for research.
C1 [Obuchowski, Nancy A.; Wang, Xiao-Feng] Cleveland Clin Fdn, Cleveland, OH 44195 USA.
[Reeves, Anthony P.] Cornell Univ, Ithaca, NY USA.
[Huang, Erich P.] NIH, Rockville, MD USA.
[Buckler, Andrew J.] Elucid Bioimaging Inc, Wenham, MA USA.
[Kim, Hyun J. (Grace)] Univ Calif Los Angeles, Los Angeles, CA USA.
[Barnhart, Huiman X.; Barboriak, Daniel P.; Sullivan, Daniel C.] Duke Univ, Durham, NC USA.
[Jackson, Edward F.] Univ Wisconsin, Madison, WI USA.
[Giger, Maryellen L.] Univ Chicago, Chicago, IL 60637 USA.
[Pennello, Gene; Myers, Kyle J.] US FDA, CDRH, Silver Spring, MD USA.
[Toledano, Alicia Y.] Biostat Consulting LLC, Kensington, MD USA.
[Kalpathy-Cramer, Jayashree] Harvard Univ, Sch Med, MGH, Boston, MA USA.
[Apanasovich, Tatiyana V.] George Washington Univ, Washington, DC USA.
[Kinahan, Paul E.] Univ Washington, Seattle, WA 98195 USA.
[Goldgof, Dmitry B.] Univ S Florida, Tampa, FL USA.
[Gillies, Robert J.] H Moffitt Canc Ctr, Tampa, FL USA.
[Schwartz, Lawrence H.] Columbia Univ, New York, NY USA.
RP Obuchowski, NA (reprint author), Cleveland Clin Fdn, Quantitat Hlth Sci JJN 3, 9500 Euclid Ave, Cleveland, OH 44195 USA.
EM obuchon@ccf.org
OI Kalpathy-Cramer, Jayashree/0000-0001-8906-9618; Jackson,
Edward/0000-0002-5958-0076; Gillies, Robert/0000-0002-8888-7747;
Buckler, Andrew/0000-0002-0786-4835; Giger,
Maryellen/0000-0001-5482-9728
FU Radiologic Society of North America (RSNA); NIH/NIBIB
[HHSN268201000050C]
FX The Radiologic Society of North America (RSNA) and NIH/NIBIB contract #
HHSN268201000050C supported two workshops and numerous conference calls
for the authors' Working Group.
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PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 0962-2802
EI 1477-0334
J9 STAT METHODS MED RES
JI Stat. Methods Med. Res.
PD FEB
PY 2015
VL 24
IS 1
SI SI
BP 68
EP 106
DI 10.1177/0962280214537390
PG 39
WC Health Care Sciences & Services; Mathematical & Computational Biology;
Medical Informatics; Statistics & Probability
SC Health Care Sciences & Services; Mathematical & Computational Biology;
Medical Informatics; Mathematics
GA CE4ZZ
UT WOS:000351840700004
PM 24919829
ER
PT J
AU Huang, EP
Wang, XF
Choudhury, KR
McShane, LM
Gonen, M
Ye, JJ
Buckler, AJ
Kinahan, PE
Reeves, AP
Jackson, EF
Guimaraes, AR
Zahlmann, G
AF Huang, Erich P.
Wang, Xiao-Feng
Choudhury, Kingshuk Roy
McShane, Lisa M.
Goenen, Mithat
Ye, Jingjing
Buckler, Andrew J.
Kinahan, Paul E.
Reeves, Anthony P.
Jackson, Edward F.
Guimaraes, Alexander R.
Zahlmann, Gudrun
CA Meta-Anal Working Grp
TI Meta-analysis of the technical performance of an imaging procedure:
Guidelines and statistical methodology
SO STATISTICAL METHODS IN MEDICAL RESEARCH
LA English
DT Article
DE quantitative imaging; imaging biomarkers; technical performance;
repeatability; reproducibility; meta-analysis; meta-regression;
systematic review
ID SEMIAUTOMATED VOLUME MEASUREMENTS; INDIVIDUAL PATIENT DATA;
META-REGRESSION; SYSTEMATIC REVIEWS; ASSESSING AGREEMENT; LUNG-CANCER;
FDG-PET; PULMONARY NODULES; MALIGNANT-TUMORS; PRISMA STATEMENT
AB Medical imaging serves many roles in patient care and the drug approval process, including assessing treatment response and guiding treatment decisions. These roles often involve a quantitative imaging biomarker, an objectively measured characteristic of the underlying anatomic structure or biochemical process derived from medical images. Before a quantitative imaging biomarker is accepted for use in such roles, the imaging procedure to acquire it must undergo evaluation of its technical performance, which entails assessment of performance metrics such as repeatability and reproducibility of the quantitative imaging biomarker. Ideally, this evaluation will involve quantitative summaries of results from multiple studies to overcome limitations due to the typically small sample sizes of technical performance studies and/or to include a broader range of clinical settings and patient populations. This paper is a review of meta-analysis procedures for such an evaluation, including identification of suitable studies, statistical methodology to evaluate and summarize the performance metrics, and complete and transparent reporting of the results. This review addresses challenges typical of meta-analyses of technical performance, particularly small study sizes, which often causes violations of assumptions underlying standard meta-analysis techniques. Alternative approaches to address these difficulties are also presented; simulation studies indicate that they outperform standard techniques when some studies are small. The meta-analysis procedures presented are also applied to actual [18F]-fluorodeoxyglucose positron emission tomography (FDG-PET) test-retest repeatability data for illustrative purposes.
C1 [Huang, Erich P.; McShane, Lisa M.] NCI, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA.
[Wang, Xiao-Feng] Cleveland Clin Fdn, Dept Quantitat Hlth Sci, Cleveland, OH 44195 USA.
[Choudhury, Kingshuk Roy] Duke Univ, Dept Radiol, Sch Med, Dept Biostat & Bioinformat, Durham, NC 27710 USA.
[Goenen, Mithat] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA.
[Ye, Jingjing] US FDA, Div Biostat, Ctr Devices & Radiol Hlth, Silver Spring, MD USA.
[Buckler, Andrew J.] Elucid Biomed Imaging Inc, Wenham, MA USA.
[Kinahan, Paul E.] Univ Washington, Dept Radiol, Seattle, WA 98195 USA.
[Reeves, Anthony P.] Cornell Univ, Sch Elect & Comp Engn, Ithaca, NY USA.
[Jackson, Edward F.] Univ Wisconsin, Dept Med Phys, Madison, WI 53706 USA.
[Guimaraes, Alexander R.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Zahlmann, Gudrun] F Hoffmann La Roche Ltd, Basel, Switzerland.
RP Huang, EP (reprint author), NCI, Div Canc Treatment & Diag, NIH, 9609 Med Ctr Dr,MSC 9735, Bethesda, MD 20892 USA.
EM erich.huang@nih.gov
OI Jackson, Edward/0000-0002-5958-0076; Buckler, Andrew/0000-0002-0786-4835
FU Radiological Society of North America; NIH/NIBIB [HHSN268201000050C]
FX The authors acknowledge and appreciate the Radiological Society of North
America and NIH/NIBIB contract # HHSN268201000050C for supporting two
workshops and numerous conference calls for the authors' Working Group.
The authors would also like to thank Huiman Barnhart and Daniel Sullivan
from Duke University and Gene Pennello, Norberto Pantoja-Galicia, Robert
Ochs, Shing Chun Benny Lam, and Mary Pastel from the FDA for their
expert advice and comments on this manuscript.
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PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 0962-2802
EI 1477-0334
J9 STAT METHODS MED RES
JI Stat. Methods Med. Res.
PD FEB
PY 2015
VL 24
IS 1
SI SI
BP 141
EP 174
DI 10.1177/0962280214537394
PG 34
WC Health Care Sciences & Services; Mathematical & Computational Biology;
Medical Informatics; Statistics & Probability
SC Health Care Sciences & Services; Mathematical & Computational Biology;
Medical Informatics; Mathematics
GA CE4ZZ
UT WOS:000351840700006
PM 24872353
ER
PT J
AU Breitner, J
Baker, L
Drye, L
Evans, D
Lyketsos, C
Ryan, L
Zandi, P
Saucedo, HH
Anau, J
Cholerton, B
Kramer, K
Casper, AS
Meinert, C
Martin, B
Jenkins, G
McCaffrey, L
Meinert, J
Vaidya, V
Abuja, A
May, P
Ashe, K
Steinberg, M
Brandt, J
Pedroso, JJ
Bergey, A
Gogel, C
Smith, L
Kraus, J
Stern, RA
Green, RC
Gavett, B
Mwicigi, J
Baldwin, L
McGowan, T
Johnson, P
Qiu, W
Frederick, J
Raghavan, S
Rossi, C
Mandell, A
Dinizo, D
Roth, MT
Porsteinsson, A
Ismail, MS
Weber, M
Brand, C
Richard, J
Stear, K
Schepp, S
Cosman, K
Martin, K
Craft, S
Dahl, D
Garrett, G
Tidwell, J
Thielke, S
Smith, L
Arbuckle, M
Strong, W
Ladenberg, J
Callaghan, M
Watson, S
Skinner, J
Bowton, K
Sabbagh, M
Belden, C
Liebsack, C
Davis, K
Arnieri, L
Malek-Ahmadi, M
Nicholson, L
Jacobson, S
Schwartz, E
Mullan, M
Luis, C
Parrish, J
Faircloth, M
Ervin, T
Girard, J
Burke, D
Keegan, A
AF Breitner, John
Baker, Laura
Drye, Lea
Evans, Denis
Lyketsos, Constantine
Ryan, Laurie
Zandi, Peter
Saucedo, Hector Hernandez
Anau, Jane
Cholerton, Brenna
Kramer, Kirise
Casper, Anne Shanldin
Meinert, Curtis
Martin, Barbara
Jenkins, Gabrielle
McCaffrey, Lee
Meinert, Jill
Vaidya, Vijay
Abuja, Alka
May, Pat
Ashe, Karen
Steinberg, Martin
Brandt, Jason
Pedroso, Julia J.
Bergey, Alyssa
Gogel, Carol
Smith, Lynn
Kraus, Jennifer
Stern, Robert A.
Green, Robert C.
Gavett, Brandon
Mwicigi, Jane
Baldwin, Lorraine
McGowan, Theresa
Johnson, Patricia
Qiu, Wendy
Frederick, Jamie
Raghavan, Sumati
Rossi, Carol
Mandell, Alan
Dinizo, Daniella
Roth, Mary Tara
Porsteinsson, Anton
Ismail, M. Saleem
Weber, Miriam
Brand, Connie
Richard, Jennifer
Stear, Kelly
Schepp, Sue
Cosman, Kelly
Martin, Kimberly
Craft, Suzanne
Dahl, Deborah
Garrett, Grace
Tidwell, Jamie
Thielke, Stephen
Smith, Lauren
Arbuckle, Matthew
Strong, William
Ladenberg, Juliet
Callaghan, Maureen
Watson, Stennis
Skinner, Jeannine
Bowton, Kaysha
Sabbagh, Marwan
Belden, Christine
Liebsack, Carolyn
Davis, Kathryn
Arnieri, Lauren
Malek-Ahmadi, Michael
Nicholson, Lisa
Jacobson, Sandra
Schwartz, Elliot
Mullan, Michael
Luis, Cheryl
Parrish, Julia
Faircloth, Marlee
Ervin, Terry
Girard, Janette
Burke, Deborah
Keegan, Andrew
CA ADAPT-FS Res Grp
TI Follow-up evaluation of cognitive function in the randomized Alzheimer's
Disease Anti-inflammatory Prevention Trial and its Follow-up Study
SO ALZHEIMERS & DEMENTIA
LA English
DT Article
DE Prevention; Clinical trial; Alzheimer's disease; Cognitive function;
Nonsteroidal anti-inflammatory drug; Naproxen; Celecoxib
ID NSAID USE; DECLINE; DRUGS; CELECOXIB; NAPROXEN; ASSOCIATION; POPULATION;
VALIDATION; ASPIRIN; SCALE
AB Objective: The Alzheimer's Disease Anti-Inflammatory Prevention Trial (ADAPT) and Follow-up Study (ADAPT-FS) examined effects of naproxen and celecoxib on cognition in the elderly. We report here results describing trajectories of cognitive evaluation test scores.
Methods: A total of 2356 participants completed baseline and at least one follow-up cognitive evaluation between 2001 and 2004. Study treatments were discontinued in 2004, but participants were followed until 2007. A total of 1537 participants were reevaluated in 2010 to 2011. Outcomes include seven cognitive evaluations administered yearly in person in ADAPT and three of these evaluations that were administered by telephone near the end of ADAPT and again in ADAPT-FS.
Results: There were no important differences over time by treatment group on any ADAPT cognitive measure, a global composite, or the three cognitive measures reassessed in ADAPT-FS by telephone.
Conclusions: Treatment for 1 to 3 years with naproxen or celecoxib did not protect against cognitive decline in older adults with a family history of AD. (C) 2015 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.
C1 [Breitner, John] Douglas Mental Hlth Univ Inst, Ctr Studies Prevent Alzheimers Dis, Montreal, PQ, Canada.
[Breitner, John] McGill Univ, Montreal, PQ, Canada.
[Baker, Laura] Veteran Affairs Puget Sound Hlth Care Syst, Seattle, WA USA.
[Baker, Laura] Univ Washington, Sch Med, Seattle, WA USA.
[Drye, Lea; Zandi, Peter; Casper, Anne Shanldin; Meinert, Curtis; Martin, Barbara; Jenkins, Gabrielle; McCaffrey, Lee; Meinert, Jill; Vaidya, Vijay; Abuja, Alka; May, Pat] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Evans, Denis] Rush Univ, Med Ctr, Chicago, IL 60612 USA.
[Lyketsos, Constantine; Steinberg, Martin; Brandt, Jason; Pedroso, Julia J.; Bergey, Alyssa; Gogel, Carol; Smith, Lynn; Kraus, Jennifer] Johns Hopkins Sch Med, Baltimore, MD USA.
[Ryan, Laurie] NIA, Bethesda, MD 20892 USA.
[Ashe, Karen] N Bud Grossman Ctr Memory Res & Care, Minneapolis, MN USA.
[Stern, Robert A.; Green, Robert C.; Gavett, Brandon; Mwicigi, Jane; Baldwin, Lorraine; McGowan, Theresa; Johnson, Patricia; Qiu, Wendy; Frederick, Jamie; Raghavan, Sumati; Rossi, Carol; Mandell, Alan; Dinizo, Daniella; Roth, Mary Tara] Boston Univ, Sch Med, Boston, MA 02118 USA.
[Porsteinsson, Anton; Ismail, M. Saleem; Weber, Miriam; Brand, Connie; Richard, Jennifer; Stear, Kelly; Schepp, Sue; Cosman, Kelly; Martin, Kimberly] Univ Rochester, Sch Med, Rochester, NY 14627 USA.
[Sabbagh, Marwan; Belden, Christine; Liebsack, Carolyn; Davis, Kathryn; Arnieri, Lauren; Malek-Ahmadi, Michael; Nicholson, Lisa; Jacobson, Sandra; Schwartz, Elliot] Sun Hlth Res Inst, Sun City, AZ USA.
[Mullan, Michael; Luis, Cheryl; Parrish, Julia; Faircloth, Marlee; Ervin, Terry; Girard, Janette; Burke, Deborah; Keegan, Andrew] Roskamp Inst Memory Clin, Tampa, FL USA.
[Evans, Denis] Rush Presbyterian St Lukes Med Ctr, Chicago, IL USA.
RP Breitner, J (reprint author), Douglas Mental Hlth Univ Inst, Ctr Studies Prevent Alzheimers Dis, Montreal, PQ, Canada.
FU National Institute on Aging (NIA) [U01 AG15477, 2U01 AG015477-06A2]; N.
Bud Grossman Center for Memory Research and Care; Minnesota Medical
Foundation
FX This study was supported by National Institute on Aging (NIA) U01
AG15477, 2U01 AG015477-06A2; N. Bud Grossman Center for Memory Research
and Care, and Minnesota Medical Foundation.
NR 29
TC 5
Z9 5
U1 2
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1552-5260
EI 1552-5279
J9 ALZHEIMERS DEMENT
JI Alzheimers. Dement.
PD FEB
PY 2015
VL 11
IS 2
BP 216
EP 225
DI 10.1016/j.jalz.2014.03.009
PG 10
WC Clinical Neurology
SC Neurosciences & Neurology
GA CD7FB
UT WOS:000351255100011
ER
PT J
AU Reynolds, MR
Sweeney, KJ
Crilly, SM
Farrell, M
Jaffe, ES
Javadpour, M
AF Reynolds, Matthew R.
Sweeney, Kieron J.
Crilly, Shane M.
Farrell, Michael
Jaffe, Elaine S.
Javadpour, Mohsen
TI Rapid, de novo development of isolated intracranial rosai-dorfman
disease: A case report
SO BRITISH JOURNAL OF NEUROSURGERY
LA English
DT Article
DE de novo development; isolated; intracranial; rosai-dorfman disease;
sinus histiocytosis with massive lymphadenopathy
AB Isolated intracranial Rosai-Dorfman Disease is rare. Here, we describe a patient who developed an asymptomatic, right parietal RDD lesion over 18 months while being followed radiographically for another brain lesion. To our knowledge, rapid, de novo radiographic formation of isolated intracranial RDD has never been reported in an asymptomatic patient.
C1 [Reynolds, Matthew R.] Washington Univ, Dept Neurol Surg, St Louis, MO USA.
[Reynolds, Matthew R.; Sweeney, Kieron J.; Crilly, Shane M.; Javadpour, Mohsen] Beaumont Hosp, Natl Ctr Neurosurg, Dept Neurol Surg, Dublin 9, Ireland.
[Farrell, Michael] Beaumont Hosp, Natl Ctr Neurosurg, Dept Neuropathol, Dublin 9, Ireland.
[Jaffe, Elaine S.] NCI, Dept Pathol, NIH, Bethesda, MD 20892 USA.
RP Reynolds, MR (reprint author), Barnes Jewish Hosp, Dept Neurol Surg, Campus Box 8057,660 South Euclid Ave, St Louis, MO 63110 USA.
EM ReynoldsM@wudosis.wustl.edu
RI Jaffe, Elaine/G-8984-2014;
OI Jaffe, Elaine/0000-0003-4632-0301; Javadpour, Mohsen/0000-0001-9836-1741
NR 3
TC 0
Z9 0
U1 0
U2 0
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 0268-8697
EI 1360-046X
J9 BRIT J NEUROSURG
JI Br. J. Neurosurg.
PD FEB
PY 2015
VL 29
IS 1
BP 82
EP 84
DI 10.3109/02688697.2014.950634
PG 3
WC Clinical Neurology; Surgery
SC Neurosciences & Neurology; Surgery
GA CE2KQ
UT WOS:000351644900018
ER
PT J
AU Cruz, MC
Ruano, G
Wolf, M
Hecker, D
Vidaurre, EC
Schmittgens, R
Rajal, VB
AF Cecilia Cruz, Mercedes
Ruano, Gustavo
Wolf, Marcus
Hecker, Dominic
Castro Vidaurre, Elza
Schmittgens, Ralph
Beatriz Rajal, Veronica
TI Plasma deposition of silver nanoparticles on ultrafiltration membranes:
Antibacterial and anti-biofouling properties
SO CHEMICAL ENGINEERING RESEARCH & DESIGN
LA English
DT Article
DE Ultrafiltration; Biofouling; Silver nanoparticles; Plasma; Gas flow
sputtering; XPS
ID SURFACE MODIFICATION; POLYPROPYLENE MEMBRANE; STAPHYLOCOCCUS-AUREUS;
ESCHERICHIA-COLI; WASTE-WATER; POLYETHERSULFONE; NANOFILTRATION;
NANOMATERIALS; PERFORMANCE; POLYMERIZATION
AB A novel and versatile plasma reactor was used to modify polyethersulphone commercial membranes. The equipment was applied to: (i) functionalize the membranes with low-temperature plasmas, (ii) deposit a film of poly(methyl methacrylate) (PMMA) by Plasma Enhanced Chemical Vapor Deposition (PECVD) and, (iii) deposit silver nanoparticles (SNP) by gas flow sputtering. Each modification process was performed in the same reactor consecutively, without exposure of the membranes to atmospheric air. Scanning electron microscopy and transmission electron microscopy were used to characterize the particles and modified membranes. SNP are evenly distributed on the membrane surface. Particle fixation and transport inside membranes were assessed before- and after-washing assays by X-ray photoelectron spectroscopy depth profiling analysis. PMMA addition improved SNP fixation. Plasma-treated membranes showed higher hydrophilicity. Anti-biofouling activity was successfully achieved against Gram-positive (Enterococcus faecalis) and -negative (Salmonella) Typhimurium bacteria. Therefore, disinfection by ultrafiltration showed substantial resistance to biofouling. The post-synthesis functionalization process developed provides a more efficient fabrication route for anti-biofouling and anti-bacterial membranes used in the water treatment field. To the best of our knowledge, this is the first report of a gas phase condensation process combined with a PECVD procedure in order to deposit SNP on commercial membranes to inhibit biofouling formation. (C) 2014 The Institution of Chemical Engineers. Published by Elsevier B.V. All rights reserved.
C1 [Cecilia Cruz, Mercedes; Castro Vidaurre, Elza; Beatriz Rajal, Veronica] Univ Nacl Salta, Inst Invest Ind Quim, Consejo Nacl Invest Cient & Tecn, Salta Capital, Argentina.
[Cecilia Cruz, Mercedes; Castro Vidaurre, Elza; Beatriz Rajal, Veronica] Univ Nacl Salta, Fac Ingn, Salta Capital, Argentina.
[Ruano, Gustavo] CNEA, Ctr Atom Bariloche, RA-8400 San Carlos De Bariloche, Rio Negro, Argentina.
[Wolf, Marcus; Hecker, Dominic; Schmittgens, Ralph] Tech Univ Dresden, Inst Festkorperelekt, D-01062 Dresden, Germany.
[Hecker, Dominic] Fraunhofer Inst Elektronenstrahl & Plasmatech, D-01277 Dresden, Germany.
[Beatriz Rajal, Veronica] Univ Calif Davis, Fogarty Int Ctr, Davis, CA 95616 USA.
RP Rajal, VB (reprint author), Consejo Nacl Invest Cient & Tecn, INIQUI, A4402FDC, RA-177 Buenos Aires, Salta Capital, Argentina.
EM vbrajal@gmail.com
FU Secretaria de Ciencia, Tecnologia e Innovacion Productiva (SECyT,
Argentina) [DA0704]; German Academic Exchange Service (DAAD, Germany)
[DA0704]; NIH - Fogarty International Center [D43 TW005718]; National
Institute of Environmental Health Sciences (USA); CONICET
FX This project was supported by the Scientific and Technological
Cooperation Program between the Secretaria de Ciencia, Tecnologia e
Innovacion Productiva (SECyT, Argentina) and the German Academic
Exchange Service (DAAD, Germany) project code DA0704. It was also
partially supported by NIH Grant D43 TW005718 funded by the Fogarty
International Center and the National Institute of Environmental Health
Sciences (USA). Mercedes Cecilia Cruz and Gustavo Ruano were supported
by CONICET fellowships. The SEM micrographs were taken in the
Laboratorio de Microscopia Electronica de Barrido (LASEM) - ANPCyT UNSa
CONICET - Salta.
NR 46
TC 7
Z9 7
U1 8
U2 43
PU INST CHEMICAL ENGINEERS
PI RUGBY
PA 165-189 RAILWAY TERRACE, DAVIS BLDG, RUGBY CV21 3HQ, ENGLAND
SN 0263-8762
EI 1744-3563
J9 CHEM ENG RES DES
JI Chem. Eng. Res. Des.
PD FEB
PY 2015
VL 94
BP 524
EP 537
DI 10.1016/j.cherd.2014.09.014
PG 14
WC Engineering, Chemical
SC Engineering
GA CC2SI
UT WOS:000350194500050
PM 26166926
ER
PT J
AU Kouprina, N
Larionov, V
AF Kouprina, Natalay
Larionov, Vladimir
TI Recent advances in chromosome engineering
SO CHROMOSOME RESEARCH
LA English
DT Article
DE Artificial chromosome; CRISPR; Gene therapy; Kinetochore; Stem cell;
Synthetic biology; TALEN; Transgenic; ZFN
ID CELLS
C1 [Kouprina, Natalay; Larionov, Vladimir] NCI, Dev Therapeut Branch, Bethesda, MD 20892 USA.
RP Kouprina, N (reprint author), NCI, Dev Therapeut Branch, Bethesda, MD 20892 USA.
EM kouprinn@mail.nih.gov; larionov@mail.nih.gov
NR 7
TC 0
Z9 0
U1 0
U2 6
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0967-3849
EI 1573-6849
J9 CHROMOSOME RES
JI Chromosome Res.
PD FEB
PY 2015
VL 23
IS 1
SI SI
BP 1
EP 5
DI 10.1007/s10577-015-9469-5
PG 5
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA CE0YU
UT WOS:000351538300001
PM 25682170
ER
PT J
AU Ohzeki, J
Larionov, V
Earnshaw, WC
Masumoto, H
AF Ohzeki, Jun-ichirou
Larionov, Vladimir
Earnshaw, William C.
Masumoto, Hiroshi
TI Genetic and epigenetic regulation of centromeres: a look at HAC
formation
SO CHROMOSOME RESEARCH
LA English
DT Review
DE Centromere; CENP-A; HAC; Kinetochore; Heterochromatin; CENP-B; HAT
ID ALPHA-SATELLITE DNA; HUMAN ARTIFICIAL CHROMOSOME; CENP-A CHROMATIN;
FUNCTIONAL HUMAN CENTROMERE; FISSION YEAST CENTROMERE; B NULL MICE;
BUDDING YEAST; HUMAN-CELLS; KINETOCHORE; HETEROCHROMATIN
AB The centromere is a specialized chromosomal locus required for accurate chromosome segregation. A specific histone H3 variant, CENP-A, assembles at centromeres. CENP-A is required for kinetochore protein assembly and is an epigenetic marker for the maintenance of a functional centromere. Human CENP-A chromatin normally assembles on alpha-satellite DNA (alphoid DNA), a centromeric repetitive sequence. Using alphoid DNA arrays, human artificial chromosomes (HACs) have been constructed in human HT1080 cells and used to dissect the requirements for CENP-A assembly on DNA sequence. However, centromere formation is not a simple genetic event. In other commonly used human cell lines, such as HeLa and U2OS cells, no functional de novo centromere formation occurs efficiently with the same centromeric alphoid DNA sequences. Recent studies using protein tethering combined with the HAC system and/or genetic manipulation have revealed that epigenetic chromatin regulation mechanisms are also involved in the CENP-A chromatin assembly pathway and subsequent centromere/kinetochore formation. We summarize the DNA sequence requirements for CENP-A assembly and discuss the epigenetic regulation of human centromeres.
C1 [Ohzeki, Jun-ichirou; Masumoto, Hiroshi] Kazusa DNA Res Inst, Dept Frontier Res, Lab Cell Engn, Kisarazu, Chiba 2920818, Japan.
[Larionov, Vladimir] NCI, Dev Therapeut Branch, NIH, Bethesda, MD 20892 USA.
[Earnshaw, William C.] Univ Edinburgh, Wellcome Trust Ctr Cell Biol, Edinburgh, Midlothian, Scotland.
RP Masumoto, H (reprint author), Kazusa DNA Res Inst, Dept Frontier Res, Lab Cell Engn, 2-6-7 Kazusa Kamatari, Kisarazu, Chiba 2920818, Japan.
EM masumoto@kazusa.or.jp
FU Intramural NIH HHS; Wellcome Trust [073915]
NR 133
TC 6
Z9 6
U1 4
U2 11
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0967-3849
EI 1573-6849
J9 CHROMOSOME RES
JI Chromosome Res.
PD FEB
PY 2015
VL 23
IS 1
SI SI
BP 87
EP 103
DI 10.1007/s10577-015-9470-z
PG 17
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA CE0YU
UT WOS:000351538300009
PM 25682171
ER
PT J
AU Nsoesie, EO
Kluberg, SA
Mekaru, SR
Majumder, MS
Khan, K
Hay, SI
Brownstein, JS
AF Nsoesie, E. O.
Kluberg, S. A.
Mekaru, S. R.
Majumder, M. S.
Khan, K.
Hay, S. I.
Brownstein, J. S.
TI New digital technologies for the surveillance of infectious diseases at
mass gathering events
SO CLINICAL MICROBIOLOGY AND INFECTION
LA English
DT Review
DE Communicable diseases; Internet; mass gatherings; novel technologies;
wireless sensor networks
ID PUBLIC-HEALTH SURVEILLANCE; FIFA WORLD CUP; SYNDROMIC SURVEILLANCE;
GEOSENTINEL EXPERIENCE; HAJJ PILGRIMAGE; LARGE OUTBREAK; AUSTRALIA;
RISKS; PREVENTION; TRAVELERS
AB Outbreaks of infectious diseases at mass gatherings can strain the health system of the host region and pose a threat to local and global health. In addition to strengthening existing surveillance systems, most host nations also use novel technologies to assess disease risk and augment traditional surveillance approaches. We review novel approaches to disease surveillance using the Internet, mobile phone applications, and wireless sensor networks. These novel approaches to disease surveillance can result in prompt detection. (C) 2015 Clinical Microbiology and Infection published by Elsevier Ltd on behalf of European Society of Clinical Microbiology and Infectious Diseases.
C1 [Nsoesie, E. O.; Kluberg, S. A.; Mekaru, S. R.; Majumder, M. S.; Brownstein, J. S.] Boston Childrens Hosp, Childrens Hosp Informat Program, Boston, MA USA.
[Nsoesie, E. O.; Brownstein, J. S.] Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA.
[Majumder, M. S.] MIT, Engn Syst Div, Cambridge, MA 02139 USA.
[Brownstein, J. S.] McGill Univ, Dept Epidemiol Biostat & Occupat Hlth, Montreal, PQ, Canada.
[Khan, K.] St Michaels Hosp, Li Ka Shing Knowledge Inst, Toronto, ON M5B 1W8, Canada.
[Hay, S. I.] Univ Oxford, Dept Zool, Spatial Ecol & Epidemiol Grp, Oxford, England.
[Hay, S. I.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Nsoesie, EO (reprint author), HealthMap BCH3409, 300 Longwood Ave, Boston, MA 02115 USA.
EM onelaine@vt.edu
RI Hay, Simon/F-8967-2015;
OI Hay, Simon/0000-0002-0611-7272; Nsoesie, Elaine/0000-0001-9170-8714
FU NLM NIH HHS [R01 LM010812]; Wellcome Trust [095066]
NR 54
TC 5
Z9 6
U1 1
U2 9
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1198-743X
EI 1469-0691
J9 CLIN MICROBIOL INFEC
JI Clin. Microbiol. Infect.
PD FEB
PY 2015
VL 21
IS 2
BP 134
EP 140
DI 10.1016/j.cmi.2014.12.017
PG 7
WC Infectious Diseases; Microbiology
SC Infectious Diseases; Microbiology
GA CE2MB
UT WOS:000351648600005
PM 25636385
ER
PT J
AU Sugui, JA
Kwon-Chung, KJ
Juvvadi, PR
Latge, JP
Steinbach, WJ
AF Sugui, Janyce A.
Kwon-Chung, Kyung J.
Juvvadi, Praveen R.
Latge, Jean-Paul
Steinbach, William J.
TI Aspergillus fumigatus and Related Species
SO COLD SPRING HARBOR PERSPECTIVES IN MEDICINE
LA English
DT Article
ID INVASIVE FUNGAL-INFECTIONS; CHRONIC GRANULOMATOUS-DISEASE;
LINKED-IMMUNOSORBENT-ASSAY; ALLERGIC BRONCHOPULMONARY ASPERGILLOSIS;
NONRIBOSOMAL PEPTIDE SYNTHETASE; EPIDEMIOLOGIC CUTOFF VALUES; HOST-CELL
INTERACTIONS; METHOD M38-A2 DOCUMENT; PROTEIN-KINASE-A; PULMONARY
ASPERGILLOSIS
AB The genus Aspergillus contains etiologic agents of aspergillosis. The clinical manifestations of the disease range from allergic reaction to invasive pulmonary infection. Among the pathogenic aspergilli, Aspergillus fumigatus is most ubiquitous in the environment and is the major cause of the disease, followed by Aspergillus flavus, Aspergillus niger, Aspergillus terreus, Aspergillus nidulans, and several species in the section Fumigati that morphologically resemble A. fumigatus. Patients that are at risk for acquiring aspergillosis are those with an altered immune system. Early diagnosis, species identification, and adequate antifungal therapy are key elements for treatment of the disease, especially in cases of pulmonary invasive aspergillosis that often advance very rapidly. Incorporating knowledge of the basic biology of Aspergillus species to that of the diseases that they cause is fundamental for further progress in the field.
C1 [Sugui, Janyce A.; Kwon-Chung, Kyung J.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
[Juvvadi, Praveen R.; Steinbach, William J.] Duke Univ, Dept Pediat, Div Pediat Infect Dis, Durham, NC 27715 USA.
[Latge, Jean-Paul] Inst Pasteur, Unite Aspergillus, F-75724 Paris, France.
[Steinbach, William J.] Duke Univ, Dept Mol Genet & Microbiol, Durham, NC 27710 USA.
RP Steinbach, WJ (reprint author), Duke Univ, Dept Pediat, Div Pediat Infect Dis, Durham, NC 27715 USA.
EM bill.steinbach@duke.edu
FU National Institute of Allergy and Infectious Diseases, National
Institutes of Health, Bethesda, MD
FX J.A.S. and K.J.K.-C. are supported by the Intramural Research Program of
the National Institute of Allergy and Infectious Diseases, National
Institutes of Health, Bethesda, MD.
NR 151
TC 5
Z9 5
U1 2
U2 11
PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
PI COLD SPRING HARBOR
PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA
SN 2157-1422
J9 CSH PERSPECT MED
JI Cold Spring Harb. Perspect. Med.
PD FEB
PY 2015
VL 5
IS 2
AR a019786
DI 10.1101/cshperspect.a019786
PG 17
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA CD6YP
UT WOS:000351237300006
ER
PT J
AU AlGhatrif, M
Lakatta, EG
AF AlGhatrif, Majd
Lakatta, Edward G.
TI The Conundrum of Arterial Stiffness, Elevated Blood Pressure, and Aging
SO CURRENT HYPERTENSION REPORTS
LA English
DT Article
DE Aging; Hypertension; Pulse wave velocity; Aortic diameter; Aortic
remodeling
ID ISOLATED SYSTOLIC HYPERTENSION; NUTRITION EXAMINATION SURVEY; PULSE-WAVE
VELOCITY; AORTIC STIFFNESS; INCIDENT HYPERTENSION; NATIONAL-HEALTH;
PROGRESSION; DISEASE; HEART; AGE
AB Isolated systolic hypertension is a major health burden that is expanding with the aging of our population. There is evidence that central arterial stiffness contributes to the rise in systolic blood pressure (SBP); at the same time, central arterial stiffening is accelerated in patients with increased SBP. This bidirectional relationship created a controversy in the field on whether arterial stiffness leads to hypertension or vice versa. Given the profound interdependency of arterial stiffness and blood pressure, this question seems intrinsically challenging, or probably naive. The aorta's function of dampening the pulsatile flow generated by the left ventricle is optimal within a physiological range of distending pressure that secures the required distal flow, keeps the aorta in an optimal mechanical conformation, and minimizes cardiac work. This homeostasis is disturbed by age-associated, minute alterations in aortic hemodynamic and mechanical properties that induce short-and long-term alterations in each other. Hence, it is impossible to detect an "initial insult" at an epidemiological level. Earlier manifestations of these alterations are observed in young adulthood with a sharp decline in aortic strain and distensibility accompanied by an increase in diastolic blood pressure. Subsequently, aortic mechanical reserve is exhausted, and aortic remodeling with wall stiffening and dilatation ensue. These two phenomena affect pulse pressure in opposite directions and different magnitudes. With early remodeling, there is an increase in pulse pressure, due to the dominance of arterial wall stiffness, which in turn accelerates aortic wall stiffness and dilation. With advanced remodeling, which appears to be greater in men, the effect of diameter becomes more pronounced and partially offsets the effect of wall stiffness leading to plateauing in pulse pressure in men and slower increase in pulse pressure (PP) than that of wall stiffness in women. The complex nature of the hemodynamic changes with aging makes the "one-size-fits-all" approach suboptimal and urges for therapies that address the vascular profile that underlies a given blood pressure, rather than the blood pressure values themselves.
C1 [AlGhatrif, Majd; Lakatta, Edward G.] NIA, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA.
[AlGhatrif, Majd] Johns Hopkins Sch Med, Dept Med, Baltimore, MD USA.
RP AlGhatrif, M (reprint author), NIA, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA.
EM Majd.alghatrif@nih.gov; LakattaE@grc.nia.nih.gov
FU Intramural NIH HHS [ZIA AG000856-13]
NR 34
TC 3
Z9 3
U1 0
U2 4
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1522-6417
EI 1534-3111
J9 CURR HYPERTENS REP
JI Curr. Hypertens. Rep.
PD FEB
PY 2015
VL 17
IS 2
AR 12
DI 10.1007/s11906-014-0523-z
PG 9
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA CE1HW
UT WOS:000351563700010
PM 25687599
ER
PT J
AU Pagani, JH
Avram, SKW
Cui, Z
Song, J
Mezey, E
Senerth, JM
Baumann, MH
Young, WS
AF Pagani, J. H.
Avram, S. K. Williams
Cui, Z.
Song, J.
Mezey, E.
Senerth, J. M.
Baumann, M. H.
Young, W. S.
TI Raphe serotonin neuron-specific oxytocin receptor knockout reduces
aggression without affecting anxiety-like behavior in male mice only
SO GENES BRAIN AND BEHAVIOR
LA English
DT Article
DE Conditional knockout; maternal aggression; oxytocin; serotonin
ID MATERNAL AGGRESSION; POSTTRAUMATIC-STRESS; VASOPRESSIN 1A; RATS;
DISORDER; DOPAMINE; NUCLEUS; ATTACHMENT; DEFICIENT; PROFILES
AB Serotonin and oxytocin influence aggressive and anxiety-like behaviors, though it is unclear how the two may interact. That the oxytocin receptor is expressed in the serotonergic raphe nuclei suggests a mechanism by which the two neurotransmitters may cooperatively influence behavior. We hypothesized that oxytocin acts on raphe neurons to influence serotonergically mediated anxiety-like, aggressive and parental care behaviors. We eliminated expression of the oxytocin receptor in raphe neurons by crossing mice expressing Cre recombinase under control of the serotonin transporter promoter (Slc6a4) with our conditional oxytocin receptor knockout line. The knockout mice generated by this cross are normal across a range of behavioral measures: there are no effects for either sex on locomotion in an open-field, olfactory habituation/dishabituation or, surprisingly, anxiety-like behaviors in the elevated O and plus mazes. There was a profound deficit in male aggression: only one of 11 raphe oxytocin receptor knockouts showed any aggressive behavior, compared to 8 of 11 wildtypes. In contrast, female knockouts displayed no deficits in maternal behavior or aggression. Our results show that oxytocin, via its effects on raphe neurons, is a key regulator of resident-intruder aggression in males but not maternal aggression. Furthermore, this reduction in male aggression is quite different from the effects reported previously after forebrain or total elimination of oxytocin receptors. Finally, we conclude that when constitutively eliminated, oxytocin receptors expressed by serotonin cells do not contribute to baseline anxiety-like behaviors or maternal care.
C1 [Pagani, J. H.; Avram, S. K. Williams; Song, J.; Senerth, J. M.; Young, W. S.] NIMH, Sect Neural Gene Regulat, NIH, DHHS, Bethesda, MD 20892 USA.
[Cui, Z.] NIDDK, Mol Signaling Sect, NIH, DHHS, Bethesda, MD 20892 USA.
[Mezey, E.] Natl Inst Dent & Craniofacial Res, Adult Stem Cell Sect, NIH, DHHS, Bethesda, MD USA.
[Baumann, M. H.] NIDA, Med Chem Sect, NIH, DHHS, Baltimore, MD USA.
RP Young, WS (reprint author), 9000 Rockville Pike,Bldg 49,Room 5A56, Bethesda, MD 20892 USA.
EM wsy@mail.nih.gov
RI Young, W Scott/A-9333-2009
OI Young, W Scott/0000-0001-6614-5112
FU NIMH [Z01-MH-002498]
FX We greatly appreciate the technical assistance of Emily Shepard and
Raquel Collier and the animal care provided by the building 49 Animal
Research Facility. This research was supported by the NIMH
(Z01-MH-002498).
NR 58
TC 7
Z9 7
U1 4
U2 14
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1601-1848
EI 1601-183X
J9 GENES BRAIN BEHAV
JI Genes Brain Behav.
PD FEB
PY 2015
VL 14
IS 2
BP 167
EP 176
DI 10.1111/gbb.12202
PG 10
WC Behavioral Sciences; Neurosciences
SC Behavioral Sciences; Neurosciences & Neurology
GA CE2FF
UT WOS:000351629000004
PM 25677455
ER
PT J
AU Mayeur, C
Kolodziej, SA
Wang, A
Xu, X
Lee, A
Yu, PB
Shen, J
Bloch, KD
Bloch, DB
AF Mayeur, Claire
Kolodziej, Starsha A.
Wang, Amy
Xu, Xin
Lee, Arthur
Yu, Paul B.
Shen, John
Bloch, Kenneth D.
Bloch, Donald B.
TI Oral administration of a bone morphogenetic protein type I receptor
inhibitor prevents the development of anemia of inflammation
SO HAEMATOLOGICA
LA English
DT Letter
DE anemia of inflammation; BMP inhibitor; hepcidin
ID HEPCIDIN EXPRESSION; CHRONIC DISEASE; IRON; RATS
C1 [Mayeur, Claire; Kolodziej, Starsha A.; Bloch, Kenneth D.; Bloch, Donald B.] Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Anesthesia Ctr Crit Care Res, Boston, MA 02114 USA.
[Mayeur, Claire; Kolodziej, Starsha A.; Yu, Paul B.; Bloch, Kenneth D.; Bloch, Donald B.] Harvard Univ, Sch Med, Boston, MA USA.
[Wang, Amy; Xu, Xin; Lee, Arthur; Shen, John] NCATS, Therapeut Rare & Neglected Dis TRND Program, NIH, Rockville, MD USA.
[Yu, Paul B.] Brigham & Womens Hosp, Dept Med, Div Cardiovasc, Boston, MA 02115 USA.
[Bloch, Kenneth D.] Massachusetts Gen Hosp, Dept Med, Cardiovasc Res Ctr, Boston, MA 02114 USA.
[Bloch, Donald B.] Massachusetts Gen Hosp, Dept Med, Ctr Immunol & Inflammatory Dis, Div Rheumatol Allergy & Immunol, Boston, MA 02114 USA.
RP Mayeur, C (reprint author), Massachusetts Gen Hosp, Dept Anesthesia Crit Care & Pain Med, Anesthesia Ctr Crit Care Res, Boston, MA 02114 USA.
EM cmayeur@mgh.harvard.edu
OI Yu, Paul/0000-0003-2145-4944
FU NIAMS NIH HHS [R01 AR057374]; NIDDK NIH HHS [R01 DK082971, R01DK082971];
NINDS NIH HHS [1X01NS070702]
NR 15
TC 10
Z9 11
U1 0
U2 2
PU FERRATA STORTI FOUNDATION
PI PAVIA
PA VIA GIUSEPPE BELLI 4, 27100 PAVIA, ITALY
SN 0390-6078
J9 HAEMATOLOGICA
JI Haematologica
PD FEB
PY 2015
VL 100
IS 2
BP E68
EP E71
DI 10.3324/haematol.2014.111484
PG 4
WC Hematology
SC Hematology
GA CD7OB
UT WOS:000351278900008
PM 25326432
ER
PT J
AU Saxena, V
Johnson, CG
Negussie, AH
Sharma, KV
Dreher, MR
Wood, BJ
AF Saxena, Vishal
Johnson, Carmen Gacchina
Negussie, Ayele H.
Sharma, Karun V.
Dreher, Matthew R.
Wood, Bradford J.
TI Temperature-sensitive liposome-mediated delivery of thrombolytic agents
SO INTERNATIONAL JOURNAL OF HYPERTHERMIA
LA English
DT Article
DE Staphylokinase; temperature sensitive liposomes; thrombolysis; tissue
plasminogen activator
ID TISSUE-PLASMINOGEN ACTIVATOR; RECOMBINANT STAPHYLOKINASE VARIANTS; ACUTE
MYOCARDIAL-INFARCTION; LOADED ECHOGENIC LIPOSOMES; ACUTE
ISCHEMIC-STROKE; THERMOSENSITIVE LIPOSOMES; IN-VIVO; ALTERED
IMMUNOREACTIVITY; DRUG-RELEASE; ACCELERATED THROMBOLYSIS
AB Background: Clinical efficacy of thrombolytic drugs is limited by lack of specific delivery and requires large therapeutic doses which increase toxicity. Encapsulating these drugs in temperature-sensitive liposomes and applying hyperthermia to deliver thrombolytic agents locally to thrombus might theoretically favourably alter the therapeutic window. The objectives of this study were to formulate liposomes encapsulating thrombolytics and assess thrombolytic activity following hyperthermia. Methods: Three liposome formulations were investigated: temperature-sensitive liposome (TSL, DPPC: DSPE-PEG2000 (mol% 95:5)), low temperature-sensitive liposome (LTSL, DPPC: MSPC:DSPE-PEG2000(mol% 85.3:9.7:5)), and traditional temperature-sensitive liposome (TTSL, DPPC: HSPC: Chol: DSPE-PEG2000 (mol% 55: 25: 15: 5)). To characterise temperature-dependent release of high molecular weight cargo from each formulation, fluorescein-conjugated dextrans (70 kDa) were loaded and release was quantified via spectrophotometry. Staphylokinase (SAK), urokinase, and tissue-type plasminogen activator were also loaded individually into each liposome formulation. Leakage at 37 degrees C and release at 38-44 degrees C were quantified via chromogenic enzymatic activity assay. Clot lysis was evaluated by measuring mass of blood clots before and after thrombolytic liposome treatment. Results: The LTSL formulation had optimal release characteristics with maximum release at 41.3 degrees C. Release of dextrans from LTSLs was observed to be 11.5 +/- 1.5%, 79.7 +/- 1.6%, and 93.6 +/- 3.7% after 15 min in plasma at 37 degrees, 39 degrees, and 41.3 degrees C, respectively. The SAK LTSL had the highest release/leakage ratio and demonstrated greater clot lysis. Conclusions: The SAK LTSL achieves significant clot lysis in vitro. When combined with local hyperthermia, the SAK LTSL potentially produces sufficient thrombolysis while minimising systemic side effects.
C1 [Saxena, Vishal; Johnson, Carmen Gacchina; Negussie, Ayele H.; Sharma, Karun V.; Dreher, Matthew R.; Wood, Bradford J.] NCI, Ctr Intervent Oncol Radiol & Imaging Sci, Ctr Clin, NIH, Bethesda, MD 20892 USA.
[Saxena, Vishal] NIH, Howard Hughes Med Inst, Res Scholars Program, Bethesda, MD 20892 USA.
[Sharma, Karun V.] Childrens Natl Med Ctr, Washington, DC 20010 USA.
RP Wood, BJ (reprint author), NIH, Radiol & Imaging Sci, 10 Ctr Dr,MSC 1182, Bethesda, MD 20892 USA.
EM bwood@mail.nih.gov
FU Center for Interventional Oncology, the Intramural Research Program of
the National Institutes of Health (NIH); Howard Hughes Medical Institute
NIH Research Scholars Program; NIH Imaging Sciences Training Program
FX This research was supported by the Center for Interventional Oncology,
the Intramural Research Program of the National Institutes of Health
(NIH), the Howard Hughes Medical Institute NIH Research Scholars Program
(V.S.), and the NIH Imaging Sciences Training Program (C.G.J.). NIH and
Biocompatibles BTG have a cooperative research and development
agreement. None of the authors have any forms of conflicts of interest
and the mention of commercial products, their source, or their use in
connection with material reported herein is not to be construed as
either an actual or implied endorsement of such products by the National
Institutes of Health. The authors alone are responsible for the content
and writing of the paper.
NR 52
TC 5
Z9 5
U1 4
U2 28
PU INFORMA HEALTHCARE
PI NEW YORK
PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA
SN 0265-6736
EI 1464-5157
J9 INT J HYPERTHER
JI Int. J. Hyperthermia
PD FEB
PY 2015
VL 31
IS 1
BP 67
EP 73
DI 10.3109/02656736.2014.991428
PG 7
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA CE1LW
UT WOS:000351574200010
PM 25766387
ER
PT J
AU Aoude, LG
Pritchard, AL
Robles-Espinoza, CD
Wadt, K
Harland, M
Choi, J
Gartside, M
Quesada, V
Johansson, P
Palmer, JM
Ramsay, AJ
Zhang, XJ
Jones, K
Symmons, J
Holland, EA
Schmid, H
Bonazzi, V
Woods, S
Dutton-Regester, K
Stark, MS
Snowden, H
van Doom, R
Montgomery, GW
Martin, NG
Keane, TM
Lopez-Otin, C
Gerdes, AM
Olsson, H
Ingvar, C
Borg, A
Gruis, NA
Trent, JM
Jonsson, G
Bishop, DT
Mann, GJ
Newton-Bishop, JA
Brown, KM
Adams, DJ
Hayward, NK
AF Aoude, Lauren G.
Pritchard, Antonia L.
Robles-Espinoza, Carla Daniela
Wadt, Karin
Harland, Mark
Choi, Jiyeon
Gartside, Michael
Quesada, Victor
Johansson, Peter
Palmer, Jane M.
Ramsay, Andrew J.
Zhang, Xijun
Jones, Kristine
Symmons, Judith
Holland, Elizabeth A.
Schmid, Helen
Bonazzi, Vanessa
Woods, Susan
Dutton-Regester, Ken
Stark, Mitchell S.
Snowden, Helen
van Doom, Remco
Montgomery, Grant W.
Martin, Nicholas G.
Keane, Thomas M.
Lopez-Otin, Carlos
Gerdes, Anne-Marie
Olsson, Hakan
Ingvar, Christian
Borg, Ake
Gruis, Nelleke A.
Trent, Jeffrey M.
Jonsson, Goran
Bishop, D. Timothy
Mann, Graham J.
Newton-Bishop, Julia A.
Brown, Kevin M.
Adams, David J.
Hayward, Nicholas K.
TI Nonsense Mutations in the Shelterin Complex Genes ACD and TERF2IP in
Familial Melanoma
SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Article
ID TELOMERE LENGTH CONTROL; POT1; VARIANTS; PREDISPOSE; QUEENSLAND; SAMPLE;
PHENOTYPE; INTERACTS; DESIGN; TUMORS
AB Background: The shelterin complex protects chromosomal ends by regulating how the telomerase complex interacts with telomeres. Following the recent finding in familial melanoma of inactivating germline mutations in POT1, encoding a member of the shelterin complex, we searched for mutations in the other five components of the shelterin complex in melanoma families.
Methods: Next-generation sequencing techniques were used to screen 510 melanoma families (with unknown genetic etiology) and control cohorts for mutations in shelterin complex encoding genes: ACD, TERF2IP, TERF1, TERF2, and TINF2. Maximum likelihood and LOD [logarithm (base 10) of odds] analyses were used. Mutation clustering was assessed with chi(2) and Fisher's exact tests. P values under .05 were considered statistically significant (one-tailed with Yates' correction).
Results: Six families had mutations in ACD and four families carried TERF2IP variants, which included nonsense mutations in both genes (p.Q320X and p.R364X, respectively) and point mutations that cosegregated with melanoma. Of five distinct mutations in ACD, four clustered in the POT1 binding domain, including p.Q320X. This clustering of novel mutations in the POT1 binding domain of ACD was statistically higher (P = .005) in melanoma probands compared with population control individuals (n = 6785), as were all novel and rare variants in both ACD (P = .040) and TERF2IP (P = .022). Families carrying ACD and TERF2IP mutations were also enriched with other cancer types, suggesting that these variants also predispose to a broader spectrum of cancers than just melanoma. Novel mutations were also observed in TERF1, TERF2, and TINF2, but these were not convincingly associated with melanoma.
Conclusions: Our findings add to the growing support for telomere dysregulation as a key process associated with melanoma susceptibility.
C1 [Aoude, Lauren G.; Pritchard, Antonia L.; Gartside, Michael; Johansson, Peter; Palmer, Jane M.; Symmons, Judith; Bonazzi, Vanessa; Woods, Susan; Dutton-Regester, Ken; Stark, Mitchell S.; Montgomery, Grant W.; Martin, Nicholas G.; Hayward, Nicholas K.] QIMR Berghofer Med Res Inst, Brisbane, Qld 4006, Australia.
[Robles-Espinoza, Carla Daniela; Keane, Thomas M.; Adams, David J.] Wellcome Trust Sanger Inst, Cambridge, England.
[Wadt, Karin; Gerdes, Anne-Marie] Rigshosp, Dept Clin Genet, DK-2100 Copenhagen, Denmark.
[Harland, Mark; Snowden, Helen; Bishop, D. Timothy; Newton-Bishop, Julia A.] Univ Leeds, Leeds Inst Canc & Pathol, Leeds, W Yorkshire, England.
[Choi, Jiyeon; Brown, Kevin M.] NCI, Lab Translat Genom, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Quesada, Victor; Ramsay, Andrew J.; Lopez-Otin, Carlos] Univ Oviedo, IUOPA, Dept Bioquim & Biol Mol, Oviedo, Spain.
[Zhang, Xijun; Jones, Kristine] SAIC Frederick Inc, Canc Genom Res Lab, NCI Frederick, Frederick, MD USA.
[van Doom, Remco; Gruis, Nelleke A.] Leiden Univ, Med Ctr, Dept Dermatol, Leiden, Netherlands.
[Olsson, Hakan; Ingvar, Christian; Borg, Ake; Jonsson, Goran] Lund Univ, Dept Clin Sci Lund, Div Oncol & Pathol, Lund, Sweden.
[Trent, Jeffrey M.] Translat Genom Inst, Phoenix, AZ USA.
[Holland, Elizabeth A.; Schmid, Helen; Mann, Graham J.] Univ Sydney, Westmead Millennium Inst, Sydney, NSW 2006, Australia.
[Holland, Elizabeth A.; Schmid, Helen; Mann, Graham J.] Melanoma Inst Australia, Sydney, NSW, Australia.
RP Aoude, LG (reprint author), QIMR Berghofer Med Res Inst, 300 Herston Rd, Brisbane, Qld 4006, Australia.
EM Lauren.Aoude@qimrberghofer.edu.au
RI Pritchard, Antonia/F-4288-2010; Stark, Mitchell/E-3542-2010; Montgomery,
Grant/B-7148-2008; Johansson, Peter/K-1053-2014; hayward,
nicholas/C-1367-2015; Quesada, Victor/B-6557-2014; Lopez-Otin,
Carlos/C-6657-2013
OI Bonazzi, Vanessa/0000-0002-2574-0334; Bishop, Tim/0000-0002-8752-8785;
Newton Bishop, Julia/0000-0001-9147-6802; Keane,
Thomas/0000-0001-7532-6898; Pritchard, Antonia/0000-0001-5336-0454;
Gruis, Nelleke/0000-0002-5210-9150; Woods, Susan/0000-0002-8955-2017;
Robles Espinoza, Carla Daniela/0000-0003-3277-7466; Stark,
Mitchell/0000-0002-4510-2161; Montgomery, Grant/0000-0002-4140-8139;
Johansson, Peter/0000-0001-7015-5452; hayward,
nicholas/0000-0003-4760-1033; Quesada, Victor/0000-0002-8398-3457;
Lopez-Otin, Carlos/0000-0001-6964-1904
FU Australia and New Zealand Banking Group Limited Trustees and
Rigshospitalet, University Hospital of Copenhagen; Cure Cancer
Australia; National Health and Medical Research Council of Australia
(NHMRC); Cancer Research UK; Wellcome Trust; Consejo Nacional de Ciencia
y Tecnologia of Mexico; Dutch Cancer Society [UL 2012-5489]; Swedish
Research Council; Swedish Cancer Society; Nordic Cancer Union; European
Research Council; Division of Cancer Epidemiology and Genetics, National
Cancer Institute; Spanish Ministry of Economy and Competitiveness; Red
Tematica de Investigacion del Cancer (RTICC); Consolider-Ingenio RNAREG
Consortium; NHMRC; Cancer Institute NSW; Cancer Council Queensland;
Melanoma Research Alliance; Aase and Ejnar Danielsens fund
FX LGA and KW are supported by PhD scholarships from the Australia and New
Zealand Banking Group Limited Trustees and Rigshospitalet, University
Hospital of Copenhagen, respectively. ALP is supported by Cure Cancer
Australia. NKH and GWM are supported by fellowships from the National
Health and Medical Research Council of Australia (NHMRC). DJA, CDRE, and
TMK were supported by Cancer Research UK and the Wellcome Trust. CDRE
was also supported by Consejo Nacional de Ciencia y Tecnologia of
Mexico. MH, JANB, and DTB were supported by Cancer Research UK. NAG and
RvD were supported by a grant from the Dutch Cancer Society (UL
2012-5489). GJ, AB, HO, and CI were supported by the Swedish Research
Council, the Swedish Cancer Society and the Nordic Cancer Union. HO was
also supported by European Research Council. KMB and JC are supported by
the Division of Cancer Epidemiology and Genetics, National Cancer
Institute. CLO is an Investigator of the Botin Foundation, and work at
his laboratory is supported by grants from the Spanish Ministry of
Economy and Competitiveness and Red Tematica de Investigacion del Cancer
(RTICC). VQ is a Ramon y Cajal fellow supported by the
Consolider-Ingenio RNAREG Consortium. The work was funded in part by the
NHMRC, Cancer Institute NSW, Cancer Council Queensland, the Melanoma
Research Alliance, and the Aase and Ejnar Danielsens fund.
NR 26
TC 24
Z9 24
U1 3
U2 8
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 FEB
PY 2015
VL 107
IS 2
AR dju408
DI 10.1093/jnci/dju408
PG 7
WC Oncology
SC Oncology
GA CD7TN
UT WOS:000351295700006
ER
PT J
AU Baker, SG
AF Baker, Stuart G.
TI A Cancer Theory Kerfuffle Can Lead to New Lines of Research
SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Editorial Material
ID IDENTIFYING DRIVER MUTATIONS; SOMATIC MUTATION; IN-VIVO; INTRATESTICULAR
GRAFTS; TISSUE MORPHOGENESIS; TUMOR-SUPPRESSOR; PROGENITOR CELLS;
FOREIGN-BODIES; MAMMARY-GLAND; COLON-CANCER
AB The standard viewpoint that cancer is a genetic disease is often stated as a fact rather than a theory. By not acknowledging that it is a theory, namely the Somatic Mutation Theory (SMT), researchers are limiting their progress. An attractive alternative to SMT is the tissue organization field theory (TOFT), which is summarized as "development gone awry." To initiate a kerfuffle, I discuss the interpretation of various results under both TOFT and SMT, including recurrent mutations, hereditary cancers, induction of tumors in transgenic experiments, remission of tumors following the inhibition of enzymes activated by mutated genes, nongenotoxic carcinogens, denervation experiments, foreign-body carcinogenesis, transplantation experiments, and tumors with zero mutations. Thinking in terms of TOFT can spur new lines of research; examples are given related to the early detection of cancer.
C1 NCI, Bethesda, MD 20892 USA.
RP Baker, SG (reprint author), NCI, 9609 Med Ctr Dr, Bethesda, MD 20892 USA.
EM sb16i@nih.gov
NR 131
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 0027-8874
EI 1460-2105
J9 JNCI-J NATL CANCER I
JI JNCI-J. Natl. Cancer Inst.
PD FEB
PY 2015
VL 107
IS 2
AR dju405
DI 10.1093/jnci/dju405
PG 8
WC Oncology
SC Oncology
GA CD7TN
UT WOS:000351295700004
ER
PT J
AU Clarke, CA
Robbins, HA
Tatalovich, Z
Lynch, CF
Pawlish, KS
Finch, JL
Hernandez, BY
Fraumeni, JF
Madeleine, MM
Engels, EA
AF Clarke, Christina A.
Robbins, Hilary A.
Tatalovich, Zaria
Lynch, Charles F.
Pawlish, Karen S.
Finch, Jack L.
Hernandez, Brenda Y.
Fraumeni, Joseph F., Jr.
Madeleine, Margaret M.
Engels, Eric A.
TI Risk of Merkel Cell Carcinoma After Solid Organ Transplantation
SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Article
ID SKIN-CANCER; HIV-INFECTION; DNA-REPAIR; CYCLOSPORINE-A; RECIPIENTS;
IMMUNOSUPPRESSION; AZATHIOPRINE; MELANOMA; KIDNEY; DAMAGE
AB Background: Solid organ transplant recipients have elevated risks of virus-related cancers, in part because of long-term immunosuppression. Merkel cell carcinoma (MCC) is an aggressive skin cancer recently found to have a viral origin, but little is known regarding the occurrence of MCC after transplant.
Methods: We linked the US Scientific Registry of Transplant Recipients with data from 15 population-based cancer registries to ascertain MCC occurrence among 189 498 solid organ transplant recipients from 1987 to 2009. Risks for MCC following transplantation were compared with the general population using standardized incidence ratios, and Poisson regression was used to compare incidence rates according to key patient and transplant characteristics. All statistical tests were two-sided.
Results: After solid organ transplantation, overall risk of MCC was increased 23.8-fold (95% confidence interval = 19.6 to 28.7, n = 110). Adjusted risks were highest among older recipients, increased with time since transplantation, and varied by organ type (all P <=.007). Azathioprine, cyclosporine, and mTOR inhibitors given for maintenance immunosuppression increased risk, and non-Hispanic white recipients on cyclosporine and azathioprine experienced increasing MCC risk with lower latitude of residence (ie, higher ultraviolet radiation exposure, P = .012).
Conclusions: MCC risk is sharply elevated after solid organ transplant, likely resulting from long-term immunosuppression. Immunosuppressive medications may act synergistically with ultraviolet radiation to increase risk.
C1 [Clarke, Christina A.] Canc Prevent Inst Calif, Fremont, CA 94538 USA.
[Clarke, Christina A.] Stanford Univ, Sch Med, Dept Hlth Res & Policy, Palo Alto, CA 94304 USA.
[Clarke, Christina A.] Stanford Canc Inst, Palo Alto, CA USA.
[Robbins, Hilary A.; Tatalovich, Zaria; Fraumeni, Joseph F., Jr.; Engels, Eric A.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Lynch, Charles F.] Univ Iowa, Dept Epidemiol, Iowa City, IA USA.
[Pawlish, Karen S.] New Jersey Dept Hlth, New Jersey State Canc Registry, Trenton, NJ USA.
[Finch, Jack L.] Colorado Dept Publ Hlth & Environm, Colorado Cent Canc Registry, Denver, CO USA.
[Hernandez, Brenda Y.] Univ Hawaii, Ctr Canc, Honolulu, HI 96822 USA.
[Madeleine, Margaret M.] Fred Hutchinson Canc Res Ctr, Program Epidemiol, Seattle, WA 98104 USA.
[Madeleine, Margaret M.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
RP Clarke, CA (reprint author), Canc Prevent Inst Calif, 2201 Walnut Ave,Suite 300, Fremont, CA 94538 USA.
EM tina@cpic.org
FU Stanford Cancer Institute; National Cancer Institute of the National
Institutes of Health
FX This work was supported in part by the Stanford Cancer Institute and the
National Cancer Institute of the National Institutes of Health.
NR 30
TC 6
Z9 6
U1 1
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-J. Natl. Cancer Inst.
PD FEB
PY 2015
VL 107
IS 2
AR dju382
DI 10.1093/jnci/dju382
PG 9
WC Oncology
SC Oncology
GA CD7TN
UT WOS:000351295700001
ER
PT J
AU Loftfield, E
Freedman, ND
Graubard, BI
Hollenbeck, AR
Shebl, FM
Mayne, ST
Sinha, R
AF Loftfield, Erikka
Freedman, Neal D.
Graubard, Barry I.
Hollenbeck, Albert R.
Shebl, Fatma M.
Mayne, Susan T.
Sinha, Rashmi
TI Coffee Drinking and Cutaneous Melanoma Risk in the NIH-AARP Diet and
Health Study
SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Article
ID BASAL-CELL CARCINOMA; MALIGNANT-MELANOMA; SOCIOECONOMIC-STATUS; COX-2
EXPRESSION; CANCER INCIDENCE; NORWEGIAN MEN; UNITED-STATES; CAFFEIC
ACID; SKIN-CANCER; DNA-DAMAGE
AB Background: Cutaneous melanoma is the fifth most common cancer in the United States. Modifiable risk factors, with the exception of exposure to ultraviolet radiation (UVR), are poorly understood. Coffee contains numerous bioactive compounds and may be associated inversely with melanoma. However, previous epidemiological evidence is limited.
Methods: Coffee intake was assessed at baseline with a food frequency questionnaire in the National Institutes of Health-AARP prospective cohort study. Among 447 357 non-Hispanic whites who were cancer-free at baseline, 2904 incident cases of malignant melanoma were identified during 4 329 044 person-years of follow-up, with a median of 10.5 years of followup. Multivariable-adjusted Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for coffee intake and subsequent melanoma risk with non-coffee drinkers as the reference group. Statistical tests were two-sided, and P values less than .05 were interpreted as statistically significant.
Results: The highest category of coffee intake was inversely associated with malignant melanoma (>= 4 cups/day: HR = 0.80, 95% CI = 0.68 to 0.93, P-trend =.01). This association was statistically significant for caffeinated (>= 4 cups/day: HR = 0.75, 95% CI = 0.64 to 0.89, P-trend =.01) but not for decaffeinated coffee (P-trend =.55).
Conclusions: Higher coffee intake was associated with a modest decrease in risk of melanoma in this large US cohort study. Additional investigations of coffee intake and its constituents, particularly caffeine, with melanoma are warranted.
C1 [Loftfield, Erikka; Shebl, Fatma M.; Mayne, Susan T.] Yale Univ, Sch Publ Hlth, New Haven, CT USA.
[Loftfield, Erikka; Freedman, Neal D.; Graubard, Barry I.; Sinha, Rashmi] NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Rockville, MD 20850 USA.
[Hollenbeck, Albert R.] AARP, Washington, DC USA.
[Shebl, Fatma M.; Mayne, Susan T.] Yale Canc Ctr, New Haven, CT USA.
RP Loftfield, E (reprint author), NCI, Div Canc Epidemiol & Genet, 9609 Med Ctr Dr 6E332, Rockville, MD 20850 USA.
EM erikka.loftfield@nih.gov
RI Sinha, Rashmi/G-7446-2015; Freedman, Neal/B-9741-2015
OI Sinha, Rashmi/0000-0002-2466-7462; Freedman, Neal/0000-0003-0074-1098
FU Yale-National Cancer Institute (NCI) predoctoral training grant [T32
CA105666]; Intramural Research Program of the National Institutes of
Health, National Cancer Institute
FX This work was supported in part by the Yale-National Cancer Institute
(NCI) predoctoral training grant T32 CA105666 to STM and by the
Intramural Research Program of the National Institutes of Health,
National Cancer Institute.
NR 39
TC 8
Z9 8
U1 8
U2 39
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 FEB
PY 2015
VL 107
IS 2
AR dju421
DI 10.1093/jnci/dju421
PG 9
WC Oncology
SC Oncology
GA CD7TN
UT WOS:000351295700011
ER
PT J
AU Ying, TL
Li, HY
Lu, L
Dimitrov, DS
Jiang, SB
AF Ying, Tianlei
Li, Haoyang
Lu, Lu
Dimitrov, Dimiter S.
Jiang, Shibo
TI Development of human neutralizing monoclonal antibodies for prevention
and therapy of MERS-CoV infections
SO MICROBES AND INFECTION
LA English
DT Article
DE Coronavirus; MERS-CoV; mAbs; Receptor binding domain (RBD)
ID EAST RESPIRATORY SYNDROME; SYNDROME CORONAVIRUS INFECTION;
RECEPTOR-BINDING DOMAIN; MONOMERIC IGG1 FC; POTENT NEUTRALIZATION; SARS
CORONAVIRUS; SPIKE PROTEIN; SAUDI-ARABIA; BAT CORONAVIRUS; ORGAN
CULTURES
AB The recent Middle East respiratory syndrome coronavirus (MERS-CoV) outbreak poses a serious threat to public health. Here, we summarize recent advances in identifying human neutralizing monoclonal antibodies (mAbs) against MERS-CoV, describe their mechanisms of action, and analyze their potential for treatment of MERS-CoV infections. (C) 2014 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.
C1 [Ying, Tianlei; Li, Haoyang; Lu, Lu; Jiang, Shibo] Fudan Univ, Shanghai Med Coll, Key Lab Med Mol Virol MOE MOH, Shanghai 200032, Peoples R China.
[Dimitrov, Dimiter S.] NCI, Prot Interact Sect, Canc & Inflammat Program, Ctr Canc Res,NIH, Frederick, MD 21702 USA.
[Jiang, Shibo] New York Blood Ctr, Lindsley F Kimball Res Inst, New York, NY 10065 USA.
RP Ying, TL (reprint author), Bldg 13,Room 606,130 Dong An Rd, Shanghai 200032, Peoples R China.
EM tlying@fudan.edu.cn
RI Lu, Lu/K-7070-2014;
OI Lu, Lu/0000-0002-2255-0391
FU National Natural Science Foundation of China; Intramural Research
Program of the NIH, National Cancer Institute, Center for Cancer
Research
FX This work was supported by grants from the National Natural Science
Foundation of China and the Intramural Research Program of the NIH,
National Cancer Institute, Center for Cancer Research.
NR 67
TC 8
Z9 11
U1 0
U2 14
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1286-4579
EI 1769-714X
J9 MICROBES INFECT
JI Microbes Infect.
PD FEB
PY 2015
VL 17
IS 2
BP 142
EP 148
DI 10.1016/j.micinf.2014.11.008
PG 7
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA CD5CQ
UT WOS:000351105900008
PM 25456101
ER
PT J
AU Chio, A
Traynor, BJ
AF Chio, Adriano
Traynor, Bryan J.
TI Biomarkers for ALS-in search of the Promised Land
SO NATURE REVIEWS NEUROLOGY
LA English
DT Editorial Material
ID AMYOTROPHIC-LATERAL-SCLEROSIS; TRIAL
AB The past year has seen some extraordinary activity in clinical amyotrophic lateral sclerosis (ALS) research. Two trials were completed, with negative results, but the discovery of novel ALS-associated genes, and body fluid and imaging biomarkers warrants cautious optimism. Here, we provide a snapshot of some of the main findings in 2014.
C1 [Chio, Adriano] Univ Turin, Rita Levi Montalcini Dept Neurosci, I-10126 Turin, Italy.
[Traynor, Bryan J.] NIA, Neuromuscular Dis Res Unit, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
RP Chio, A (reprint author), Univ Turin, Rita Levi Montalcini Dept Neurosci, Via Cherasco 15, I-10126 Turin, Italy.
EM achio@usa.net
OI Chio, Adriano/0000-0001-9579-5341
FU Italian Health Ministry [RF-2010-2309849]; European Community [259867,
278611]; Joint Programme-Neurodegenerative Disease Research - Italian
Ministry of Health (Sophia Project); Joint Programme-Neurodegenerative
Disease Research - Italian Ministry of University and Research (ALS-CARE
Project); Joint Programme-Neurodegenerative Disease Research - Italian
Ministry of University and Research (Strength Project); intramural
Research Programs of the US National Institutes of Health (NIH),
National Institute on Aging [Z01-AG000949-02]; NINDS
FX A.C. is currently funded by Italian Health Ministry grant
RF-2010-2309849, European Community's Health Seventh Framework Programme
(FP7/2007-2013) under grant agreements 259867 and 278611, and the Joint
Programme-Neurodegenerative Disease Research granted by Italian Ministry
of Health (Sophia Project) and by Italian Ministry of University and
Research (ALS-CARE and Strength Projects). B.J.T. is currently funded by
intramural Research Programs of the US National Institutes of Health
(NIH), National Institute on Aging (Z01-AG000949-02) and NINDS.
NR 10
TC 6
Z9 6
U1 2
U2 4
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1759-4758
EI 1759-4766
J9 NAT REV NEUROL
JI Nat. Rev. Neurol.
PD FEB
PY 2015
VL 11
IS 2
DI 10.1038/nrneurol.2014.250
PG 2
WC Clinical Neurology
SC Neurosciences & Neurology
GA CE0SC
UT WOS:000351514800003
PM 25534912
ER
PT J
AU Henrich, CJ
Brooks, AD
Erickson, KL
Thomas, CL
Bokesch, HR
Tewary, P
Thompson, CR
Pompei, RJ
Gustafson, KR
McMahon, JB
Sayers, TJ
AF Henrich, C. J.
Brooks, A. D.
Erickson, K. L.
Thomas, C. L.
Bokesch, H. R.
Tewary, P.
Thompson, C. R.
Pompei, R. J.
Gustafson, K. R.
McMahon, J. B.
Sayers, T. J.
TI Withanolide E sensitizes renal carcinoma cells to TRAIL-induced
apoptosis by increasing cFLIP degradation
SO CELL DEATH & DISEASE
LA English
DT Article
ID HUMAN-MELANOMA CELLS; CANCER-CELLS; C-FLIP; DOWN-REGULATION; MEDIATED
APOPTOSIS; INHIBITOR PS-341; UP-REGULATION; WITHAFERIN-A; LIGAND TRAIL;
TUMOR-CELLS
AB Withanolide E, a steroidal lactone from Physalis peruviana, was found to be highly active for sensitizing renal carcinoma cells and a number of other human cancer cells to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-mediated apoptosis. Withanolide E, the most potent and least toxic of five TRAIL-sensitizing withanolides identified, enhanced death receptor-mediated apoptotic signaling by a rapid decline in the levels of cFLIP proteins. Other mechanisms by which TRAIL sensitizers have been reported to work: generation of reactive oxygen species (ROS), changes in pro-and antiapoptotic protein expression, death receptor upregulation, activation of intrinsic (mitochondrial) apoptotic pathways, ER stress, and proteasomal inhibition proved to be irrelevant to withanolide E activity. Loss of cFLIP proteins was not due to changes in expression, but rather destabilization and/or aggregation, suggesting impairment of chaperone proteins leading to degradation. Indeed, withanolide E treatment altered the stability of a number of HSP90 client proteins, but with greater apparent specificity than the well-known HSP90 inhibitor geldanamycin. As cFLIP has been reported to be an HSP90 client, this provides a potentially novel mechanism for sensitizing cells to TRAIL. Sensitization of human renal carcinoma cells to TRAIL-induced apoptosis by withanolide E and its lack of toxicity were confirmed in animal studies. Owing to its novel activity, withanolide E is a promising reagent for the analysis of mechanisms of TRAIL resistance, for understanding HSP90 function, and for further therapeutic development. In marked contrast to bortezomib, among the best currently available TRAIL sensitizers, withanolide E's more specific mechanism of action suggests minimal toxic side effects.
C1 [Henrich, C. J.; Erickson, K. L.; Thomas, C. L.; Bokesch, H. R.; Gustafson, K. R.; McMahon, J. B.] NCI, Mol Targets Lab, Frederick, MD 21702 USA.
[Henrich, C. J.; Brooks, A. D.; Bokesch, H. R.; Tewary, P.; Sayers, T. J.] Leidos Biomed Res Inc, Basic Res Program, Frederick Natl Lab Canc Res, Frederick, MD USA.
[Brooks, A. D.; Tewary, P.; Thompson, C. R.; Pompei, R. J.; Sayers, T. J.] NCI, Lab Expt Immunol, Frederick, MD 21702 USA.
[Brooks, A. D.; Tewary, P.; Thompson, C. R.; Pompei, R. J.; Sayers, T. J.] NCI, Canc Inflammat Program, Frederick, MD 21702 USA.
[Erickson, K. L.] Clark Univ, Dept Chem, Worcester, MA 01610 USA.
RP Henrich, CJ (reprint author), NCI, Basic Res Program, Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Bldg 538,Room 167, Frederick, MD 21702 USA.
EM henrichcj@mail.nih.gov
RI Sayers, Thomas/G-4859-2015
FU Federal funds from the Frederick; Laboratory for Cancer Research,
National Institutes of Health [HHSN261200800001E]; Intramural Research
Program of NIH, Frederick National Lab, Center for Cancer Research
FX This project has been funded in whole or in part with Federal funds from
the Frederick. Laboratory for Cancer Research, 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 US
Government. This research was supported (in part) by the Intramural
Research Program of NIH, Frederick National Lab, Center for Cancer
Research. NCI-Frederick is accredited by AAALAC International and
follows the Public Health Service Policy for the Care and Use of
Laboratory Animals. Animal care was provided in accordance with the
procedures outlined in the 'Guide for Care and Use of Laboratory
Animals' (National Research Council; 1996; National Academy Press;
Washington, DC). We thank Dr. Avi Ashkenazi (Genentech) for advice on
the administration of drozitumab for in vivo studies.
NR 58
TC 13
Z9 13
U1 3
U2 7
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-4889
J9 CELL DEATH DIS
JI Cell Death Dis.
PD FEB
PY 2015
VL 6
AR e1666
DI 10.1038/cddis.2015.38
PG 10
WC Cell Biology
SC Cell Biology
GA CC7VF
UT WOS:000350575800038
PM 25719250
ER
PT J
AU Love, CB
Arnesen, SJ
Phillips, SJ
AF Love, Cynthia B.
Arnesen, Stacey J.
Phillips, Steven J.
TI Ebola Outbreak Response: The Role of Information Resources and the
National Library of Medicine
SO DISASTER MEDICINE AND PUBLIC HEALTH PREPAREDNESS
LA English
DT Article
DE disease outbreaks; crowdsourcing; social media; mass media; Internet
AB The US National Library of Medicine (NLM) offers Internet-based, no-cost resources useful for responding to the 2014 West Africa Ebola outbreak. Resources for health professionals, planners, responders, and researchers include PubMed, Disaster Lit, the Web page Ebola Outbreak 2014: Information Resources, and the Virus Variation database of sequences for Ebolavirus. In cooperation with participating publishers, NLM offers free access to full-text articles from over 650 biomedical journals and 4000 online reference books through the Emergency Access Initiative. At the start of a prolonged disaster event or disease outbreak, the documents and information of most immediate use may not be in the peer-reviewed biomedical journal literature. To maintain current awareness may require using any of the following: news outlets; social media; preliminary online data, maps, and situation reports; and documents published by nongovernmental organizations, international associations, and government agencies. Similar to the pattern of interest shown in the news and social media, use of NLM Ebola-related resources is also increasing since the start of the outbreak was first reported in March 2014 (Disaster Med Public Health Preparedness. 2014;0:1-4)
C1 [Love, Cynthia B.; Arnesen, Stacey J.] Natl Lib Med, Disaster Informat Management Res Ctr, Specialized Informat Serv Div, Bethesda, MD USA.
[Phillips, Steven J.] Natl Lib Med, Specialized Informat Serv, Bethesda, MD USA.
RP Love, CB (reprint author), NIH, Disaster Informat Management Res Ctr, Specialized Informat Serv, Natl Lib Med,US Dept HHS, 6707 Democracy Blvd,Suite 510, Bethesda, MD 20892 USA.
EM cindy_love@nlm.nih.gov
FU American Academy of Pediatrics; American Association for the Advancement
of Science; American Chemical Society; American College of Physicians;
American Medical Association; American Society of Health-Systems
Pharmacists; American Society for Microbiology; B.C. Decker; BMJ;
EBSCOHost; Elsevier; FA Davis; Mary Ann Liebert; Massachusetts Medical
Society; McGraw-Hill; Merck Publishing; Oxford University Press;
People's Medical Publishing House; Springer; University of Chicago
Press; Wiley; Wolters Kluwer
FX The NLM thanks the numerous participating publishers for their generous
support of the EAI initiative: American Academy of Pediatrics, American
Association for the Advancement of Science, American Chemical Society,
American College of Physicians, American Medical Association, American
Society of Health-Systems Pharmacists, American Society for
Microbiology, B.C. Decker, BMJ, EBSCOHost, Elsevier, FA Davis, Mary Ann
Liebert, Massachusetts Medical Society, McGraw-Hill, Merck Publishing,
Oxford University Press, People's Medical Publishing House, Springer,
University of Chicago Press, Wiley, and Wolters Kluwer.
NR 6
TC 2
Z9 2
U1 5
U2 31
PU CAMBRIDGE UNIV PRESS
PI NEW YORK
PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA
SN 1935-7893
EI 1938-744X
J9 DISASTER MED PUBLIC
JI Dis. Med. Public Health Prep.
PD FEB
PY 2015
VL 9
IS 1
BP 82
EP 85
DI 10.1017/dmp.2014.108
PG 4
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA CC9DR
UT WOS:000350668600018
PM 25325189
ER
PT J
AU Horton, JK
Gassman, NR
Dunigan, BD
Stefanick, DF
Wilson, SH
AF Horton, Julie K.
Gassman, Natalie R.
Dunigan, Brittany D.
Stefanick, Donna F.
Wilson, Samuel H.
TI DNA polymerase beta-dependent cell survival independent of XRCC1
expression
SO DNA REPAIR
LA English
DT Article
DE DNA polymerase beta; XRCC1; Methyl methanesulfonate; PARP inhibitor;
Camptothecin
ID BASE-EXCISION-REPAIR; STRAND-BREAK REPAIR; PARP INHIBITION; DAMAGE;
HYPERSENSITIVITY; REQUIREMENT; INVOLVEMENT; DEFICIENCY; PROTEIN; LESIONS
AB Base excision repair (BER) is a primary mechanism for repair of base lesions in DNA such as those formed by exposure to the DNA methylating agent methyl methanesulfonate (MMS). Both DNA polymerase 13 (pol beta)- and XRCC1 -deficient mouse fibroblasts are hypersensitive to MMS. This is linked to a repair deficiency as measured by accumulation of strand breaks and poly(ADP-ribose) (PAR). The interaction between pol 13 and XRCC1 is important for recruitment of pol beta to sites of DNA damage. Endogenous DNA damage can substitute for MMS-induced damage such that BER deficiency as a result of either pol beta- or XRCC1 -deletion is associated with sensitivity to PARP inhibitors. Pol beta shRNA was used to knock down pol beta in Xrcc1(+/+) and Xrcc1(-/-) mouse fibroblasts. We determined whether pol beta-mediated cellular resistance to MMS and PARP inhibitors resulted entirely from coordination with XRCC1 within the same BER sub-pathway. We find evidence for pol beta-dependent cell survival independent of XRCC1 expression for both types of agents. The results suggest a role for pol beta-dependent, XRCC1-independent repair. PAR immunofluorescence data are consistent with the hypothesis of a decrease in repair in both pol beta knock down cell variants. Published by Elsevier B.V.
C1 [Horton, Julie K.; Gassman, Natalie R.; Dunigan, Brittany D.; Stefanick, Donna F.; Wilson, Samuel H.] NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA.
RP Wilson, SH (reprint author), NIEHS, Struct Biol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
EM wilson5@niehs.nih.gov
FU Intramural Research Program of the NIH, National Institute of
Environmental Health Sciences [Z01 ES050158, ES050159]
FX This work was supported by the Intramural Research Program of the NIH,
National Institute of Environmental Health Sciences (project numbers Z01
ES050158 and ES050159).
NR 28
TC 2
Z9 2
U1 0
U2 1
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1568-7864
EI 1568-7856
J9 DNA REPAIR
JI DNA Repair
PD FEB
PY 2015
VL 26
BP 23
EP 29
DI 10.1016/j.dnarep.2014.11.008
PG 7
WC Genetics & Heredity; Toxicology
SC Genetics & Heredity; Toxicology
GA CD2PS
UT WOS:000350922100003
PM 25541391
ER
PT J
AU Bogaerts, J
Sydes, MR
Keat, N
McConnell, A
Benson, A
Ho, A
Rotha, A
Fortpied, C
Eng, C
Peckitt, C
Coens, C
Pettaway, C
Arnold, D
Hall, E
Marshall, E
Sclafani, F
Hatcher, H
Earl, H
Ray-Coquard, I
Paul, J
Blay, JY
Whelan, J
Panageas, K
Wheatley, K
Harrington, K
Licitra, L
Billingham, L
Hensley, M
McCabe, M
Patel, PM
Carvajal, R
Wilson, R
Glynne-Jones, R
McWilliams, R
Leyvraz, S
Rao, S
Nicholson, S
Filiaci, V
Negrouk, A
Lacombe, D
Dupont, E
Pauporte, I
Welch, JJ
Law, K
Trimble, T
Seymour, M
AF Bogaerts, Jan
Sydes, Matthew R.
Keat, Nicola
McConnell, Andrea
Benson, Al
Ho, Alan
Rotha, Arnaud
Fortpied, Catherine
Eng, Cathy
Peckitt, Clare
Coens, Corneel
Pettaway, Curtis
Arnold, Dirk
Hall, Emma
Marshall, Ernie
Sclafani, Francesco
Hatcher, Helen
Earl, Helena
Ray-Coquard, Isabelle
Paul, James
Blay, Jean-Yves
Whelan, Jeremy
Panageas, Kathy
Wheatley, Keith
Harrington, Kevin
Licitra, Lisa
Billingham, Lucinda
Hensley, Martee
McCabe, Martin
Patel, Poulam M.
Carvajal, Richard
Wilson, Richard
Glynne-Jones, Rob
McWilliams, Rob
Leyvraz, Serge
Rao, Sheela
Nicholson, Steve
Filiaci, Virginia
Negrouk, Anastassia
Lacombe, Denis
Dupont, Elisabeth
Pauporte, Iris
Welch, John J.
Law, Kate
Trimble, Ted
Seymour, Matthew
TI Clinical trial designs for rare diseases: Studies developed and
discussed by the International Rare Cancers Initiative
SO EUROPEAN JOURNAL OF CANCER
LA English
DT Review
DE Rare cancers; Clinical trials; Randomised controlled trials;
Methodology; Frequentist; Bayesian; Multi-arm
ID RANDOMIZED CONTROLLED-TRIAL; UTERINE LEIOMYOSARCOMA; CHOROIDAL MELANOMA;
ADJUVANT THERAPY; UVEAL MELANOMA; SURVIVAL; CARCINOMA; EPIDEMIOLOGY;
STATISTICS; STAMPEDE
AB Background: The past three decades have seen rapid improvements in the diagnosis and treatment of most cancers and the most important contributor has been research. Progress in rare cancers has been slower, not least because of the challenges of undertaking research.
Settings: The International Rare Cancers Initiative (IRCI) is a partnership which aims to stimulate and facilitate the development of international clinical trials for patients with rare cancers. It is focused on interventional usually randomised clinical trials with the clear goal of improving outcomes for patients. The key challenges are organisational and methodological. A multi-disciplinary workshop to review the methods used in ICRI portfolio trials was held in Amsterdam in September 2013. Other as-yet unrealised methods were also discussed.
Results: The IRCI trials are each presented to exemplify possible approaches to designing credible trials in rare cancers. Researchers may consider :these for use in future trials and understand the choices made for each design.
Interpretation: Trials can be designed using a wide array of possibilities. There is no 'one size fits all' solution. In order to make progress in the rare diseases, decisions to change practice will have to be based on less direct evidence from clinical trials than in more common diseases. (C) 2014 The Authors. Published by Elsevier Ltd.
C1 [Bogaerts, Jan; Fortpied, Catherine; Coens, Corneel; Negrouk, Anastassia; Lacombe, Denis] EORTC, Brussels, Belgium.
[Sydes, Matthew R.] UCL, Med Res Council Clin Trial Unit, London WC1E 6BT, England.
[Keat, Nicola; McConnell, Andrea; Law, Kate] Canc Res UK, London, England.
[Ho, Alan; Panageas, Kathy; Hensley, Martee; Carvajal, Richard] Mem Sloan Kettering Canc Ctr, New York, NY USA.
[Eng, Cathy; Pettaway, Curtis] Univ Texas MD Anderson Canc Ctr, Houston, TX USA.
[Peckitt, Clare; Sclafani, Francesco; Rao, Sheela] Royal Marsden, London, England.
[Arnold, Dirk] Univ Canc Ctr Hamburg, Hubertus Wald Tumorzentrum, Hamburg, Germany.
[Hall, Emma; Harrington, Kevin] Inst Canc Res, London SW3 6JB, England.
[Marshall, Ernie] Univ Liverpool, Liverpool L69 3BX, Merseyside, England.
[Hatcher, Helen; Earl, Helena] Univ Cambridge, Dept Oncol, Cambridge CB2 1TN, England.
[Hatcher, Helen; Earl, Helena] NIHR Cambridge Biomed Res Ctr, Cambridge, England.
[Ray-Coquard, Isabelle; Blay, Jean-Yves] Leon Berard Canc Ctr, Lyon, France.
[Paul, James] Univ Glasgow, Inst Canc Sci, Canc Res UK Clin Trials Unit, Glasgow G12 8QQ, Lanark, Scotland.
[Whelan, Jeremy] Univ Coll London Hosp, Biomed Res Ctr, NIHR, London, England.
[Wheatley, Keith] Univ Birmingham, Birmingham B15 2TT, W Midlands, England.
[Licitra, Lisa] Ist Nazl Tumori, I-20133 Milan, Italy.
[Billingham, Lucinda] Univ Birmingham, Canc Res UK Clin Trials Unit, Birmingham B15 2TT, W Midlands, England.
[Billingham, Lucinda] Univ Birmingham, MRC Midland Hub Trials Methodol Res, Birmingham B15 2TT, W Midlands, England.
[Billingham, Lucinda] Univ Manchester, Manchester M13 9PL, Lancs, England.
[Wilson, Richard] Queens Univ Belfast, Belfast BT7 1NN, Antrim, North Ireland.
[McWilliams, Rob] Mayo Clin, Rochester, MN USA.
[Leyvraz, Serge] CHU Vaudois, Lausanne, Switzerland.
[Nicholson, Steve] Locum Consultant Med Oncol, London, England.
[Filiaci, Virginia] NRG Oncol, Gynecol Oncol Grp, Orange, CA USA.
[Dupont, Elisabeth; Welch, John J.; Trimble, Ted] US Natl Canc Inst, Ctr Global Hlth, Bethesda, MD USA.
[Pauporte, Iris] Natl Canc Inst, Boulogne, France.
[Benson, Al] Northwestern Univ, Robert H Lurie Comprehens Canc Ctr, Evanston, IL 60208 USA.
[Rotha, Arnaud] Univ Hosp Geneva, Med Oncol, Geneva, Switzerland.
[Patel, Poulam M.] Univ Nottingham, Nottingham NG7 2RD, England.
[Glynne-Jones, Rob] Mt Vernon Canc Ctr, Northwood, Middx, England.
RP Bogaerts, J (reprint author), EORTC, Brussels, Belgium.
RI McCabe, Martin/P-5896-2015; Blay, Jean-Yves/N-3966-2016; Licitra,
Lisa/C-6271-2017;
OI McCabe, Martin/0000-0002-5138-0707; Blay, Jean-Yves/0000-0001-7190-120X;
Licitra, Lisa/0000-0003-0623-4118; Hall, Emma/0000-0001-5999-5020; Earl,
Helena/0000-0003-1549-8094; Sydes, Matthew/0000-0002-9323-1371
FU Medical Research Council; NCI NIH HHS [U10 CA027469, U10 CA037517, U10
CA180822, P30 CA016672, U10 CA180868, UG1 CA189867]
NR 44
TC 22
Z9 22
U1 0
U2 8
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0959-8049
EI 1879-0852
J9 EUR J CANCER
JI Eur. J. Cancer
PD FEB
PY 2015
VL 51
IS 3
BP 271
EP 281
DI 10.1016/j.ejca.2014.10.027
PG 11
WC Oncology
SC Oncology
GA CD1KP
UT WOS:000350834100001
PM 25542058
ER
PT J
AU Espey, MG
AF Espey, Michael Graham
TI Redox physical oncology: intersections between redox and the physical
environment in cancer
SO FREE RADICAL BIOLOGY AND MEDICINE
LA English
DT Editorial Material
C1 NCI, Div Canc Biol, Rockville, MD 20850 USA.
RP Espey, MG (reprint author), NCI, Div Canc Biol, Rockville, MD 20850 USA.
EM sp@nih.gov
NR 10
TC 0
Z9 0
U1 2
U2 7
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0891-5849
EI 1873-4596
J9 FREE RADICAL BIO MED
JI Free Radic. Biol. Med.
PD FEB
PY 2015
VL 79
BP 251
EP 252
DI 10.1016/j.freeradbiomed.2014.11.023
PG 2
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA CC5IS
UT WOS:000350392900023
PM 25496800
ER
PT J
AU Huh, WK
Ault, KA
Chelmow, D
Davey, DD
Goulart, RA
Garcia, FAR
Kinney, WK
Massad, LS
Mayeaux, EJ
Saslow, D
Schiffman, M
Wentzensen, N
Lawson, HW
Einstein, MH
AF Huh, Warner K.
Ault, Kevin A.
Chelmow, David
Davey, Diane D.
Goulart, Robert A.
Garcia, Francisco A. R.
Kinney, Walter K.
Massad, L. Stewart
Mayeaux, Edward J.
Saslow, Debbie
Schiffman, Mark
Wentzensen, Nicolas
Lawson, Herschel W.
Einstein, Mark H.
TI Use of primary high-risk human papillomavirus testing for cervical
cancer screening: Interim clinical guidance
SO GYNECOLOGIC ONCOLOGY
LA English
DT Editorial Material
ID LIQUID-BASED CYTOLOGY; FOLLOW-UP; WOMEN; TRIAL; COLPOSCOPY; PREVENTION;
SERVICES; FINLAND
AB In 2011, the American Cancer Society, the American Society for Colposcopy and Cervical Pathology, and the American Society for Clinical Pathology updated screening guidelines for the early detection of cervical cancer and its precursors. Recommended screening strategies were cytology and cotesting (cytology in combination with hrHPV testing). These guidelines also addressed the use of hrHPV testing alone as a primary screening approach, which was not recommended for use at that time. There is now a growing body of evidence for screening with primary hrHPV testing, including a prospective US-based registration study. Thirteen experts including representatives from the Society of Gynecologic Oncology, American Society for Colposcopy and Cervical Pathology, American College of Obstetricians and Gynecologists, American Cancer Society, American Society of Cytopathology, College of American Pathologists, and the American Society for Clinical Pathology, convened to provide interim guidance for primary hrHPV screening. This guidance panel was specifically triggered by an application to the FDA for a currently marketed HPV test to be labeled for the additional indication of primary cervical cancer screening. Guidance was based on literature review and review of data from the FDA registration study, supplemented by expert opinion. This document aims to provide information for healthcare providers who are interested in primary hrHPV testing and an overview of the potential advantages and disadvantages of this strategy for screening as well as to highlight areas in need of further investigation. (C) 2014 the Society of Gynecologic Oncology and the American Society for Colposcopy and Cervical Pathology. Published by Elsevier Inc. All rights reserved.
C1 [Huh, Warner K.] Univ Alabama Birmingham, Birmingham, AL USA.
[Ault, Kevin A.] Univ Kansas, Med Ctr, Kansas City, KS 66103 USA.
[Chelmow, David] Virginia Commonwealth Univ, Med Ctr, Richmond, VA USA.
[Davey, Diane D.] Univ Cent Florida, Orlando, FL 32816 USA.
[Goulart, Robert A.] New England Pathol Associates, Springfield, MA USA.
[Garcia, Francisco A. R.] Pima Cty Hlth Dept, Tucson, AZ USA.
[Kinney, Walter K.] Kaiser Permanente, Sacramento, CA USA.
[Massad, L. Stewart] Washington Univ, Sch Med, St Louis, MO USA.
[Mayeaux, Edward J.] Univ S Carolina, Sch Med, Columbia, SC USA.
[Saslow, Debbie] Amer Canc Soc, Atlanta, GA 30329 USA.
[Schiffman, Mark; Wentzensen, Nicolas] NCI, Bethesda, MD 20892 USA.
[Lawson, Herschel W.] Amer Soc Colposcopy & Cerv Pathol, Frederick, MD USA.
[Einstein, Mark H.] Albert Einstein Coll Med, Bronx, NY 10467 USA.
RP Huh, WK (reprint author), Div Gynecol Oncol, 1700 6th Ave South,WIC Room 10250, Birmingham, AL 35233 USA.
EM whuh@uabmc.edu
RI Schiffman, Mark/B-9766-2015
NR 23
TC 63
Z9 74
U1 4
U2 10
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0090-8258
EI 1095-6859
J9 GYNECOL ONCOL
JI Gynecol. Oncol.
PD FEB
PY 2015
VL 136
IS 2
BP 178
EP 182
DI 10.1016/j.ygyno.2014.12.022
PG 5
WC Oncology; Obstetrics & Gynecology
SC Oncology; Obstetrics & Gynecology
GA CC7DI
UT WOS:000350527500002
PM 25579107
ER
PT J
AU Toporcov, TN
Znaor, A
Zhang, ZF
Yu, GP
Winn, DM
Wei, Q
Vilensky, M
Vaughan, T
Thomson, P
Talamini, R
Szeszenia-Dabrowska, N
Sturgis, EM
Smith, E
Shangina, O
Schwartz, SM
Schantz, S
Rudnai, P
Richiardi, L
Ramroth, H
Purdue, MP
Olshan, AF
Eluf-Neto, J
Muscat, J
Moyses, RA
Morgenstern, H
Menezes, A
McClean, M
Matsuo, K
Mates, D
Macfarlane, TV
Lissowska, J
Levi, F
Lazarus, P
La Vecchia, C
Lagiou, P
Koifman, S
Kjaerheim, K
Kelsey, K
Holcatova, I
Herrero, R
Healy, C
Hayes, RB
Franceschi, S
Fernandez, L
Fabianova, E
Daudt, AW
Curioni, OA
Dal Maso, L
Curado, MP
Conway, DI
Chen, C
Castellsague, X
Canova, C
Cadoni, G
Brennan, P
Boccia, S
Antunes, JLF
Ahrens, W
Agudo, A
Boffetta, P
Hashibe, M
Lee, YCA
Wuensch, V
AF Toporcov, Tatiana Natasha
Znaor, Ariana
Zhang, Zuo-Feng
Yu, Guo-Pei
Winn, Deborah M.
Wei, Qingyi
Vilensky, Marta
Vaughan, Thomas
Thomson, Peter
Talamini, Renato
Szeszenia-Dabrowska, Neonila
Sturgis, Erich M.
Smith, Elaine
Shangina, Oxana
Schwartz, Stephen M.
Schantz, Stimson
Rudnai, Peter
Richiardi, Lorenzo
Ramroth, Heribert
Purdue, Mark P.
Olshan, Andrew F.
Eluf-Neto, Jose
Muscat, Joshua
Moyses, Raquel Ajub
Morgenstern, Hal
Menezes, Ana
McClean, Michael
Matsuo, Keitaro
Mates, Dana
Macfarlane, Tatiana V.
Lissowska, Jolanta
Levi, Fabio
Lazarus, Philip
La Vecchia, Carlo
Lagiou, Pagona
Koifman, Sergio
Kjaerheim, Kristina
Kelsey, Karl
Holcatova, Ivana
Herrero, Rolando
Healy, Claire
Hayes, Richard B.
Franceschi, Silvia
Fernandez, Leticia
Fabianova, Eleonora
Daudt, Alexander W.
Curioni, Otavio Alberto
Dal Maso, Luigino
Curado, Maria Paula
Conway, David I.
Chen, Chu
Castellsague, Xavier
Canova, Cristina
Cadoni, Gabriella
Brennan, Paul
Boccia, Stefania
Antunes, Jose Leopoldo Ferreira
Ahrens, Wolfgang
Agudo, Antonio
Boffetta, Paolo
Hashibe, Mia
Lee, Yuan-Chin Amy
Wuensch Filho, Victor
TI Risk factors for head and neck cancer in young adults: a pooled analysis
in the INHANCE consortium
SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE Head and neck neoplasms; adult; smoking; alcohol drinking; diet
ID SQUAMOUS-CELL CARCINOMA; UPPER AERODIGESTIVE TRACT; AGED 45 YEARS;
ORAL-CANCER; PHARYNGEAL CANCER; TOBACCO USE; EPIDEMIOLOGY CONSORTIUM;
GENETIC SUSCEPTIBILITY; HUMAN-PAPILLOMAVIRUS; INTERNATIONAL HEAD
AB Background: Increasing incidence of head and neck cancer (HNC) in young adults has been reported. We aimed to compare the role of major risk factors and family history of cancer in HNC in young adults and older patients.
Methods: We pooled data from 25 case-control studies and conducted separate analyses for adults <= 45 years old ('young adults', 2010 cases and 4042 controls) and > 45 years old ('older adults', 17 700 cases and 22 704 controls). Using logistic regression with studies treated as random effects, we estimated adjusted odds ratios (ORs) and 95% confidence intervals (CIs).
Results: The young group of cases had a higher proportion of oral tongue cancer (16.0% in women; 11.0% in men) and unspecified oral cavity / oropharynx cancer (16.2%; 11.1%) and a lower proportion of larynx cancer (12.1%; 16.6%) than older adult cases. The proportions of never smokers or never drinkers among female cases were higher than among male cases in both age groups. Positive associations with HNC and duration or pack-years of smoking and drinking were similar across age groups. However, the attributable fractions (AFs) for smoking and drinking were lower in young when compared with older adults (AFs for smoking in young women, older women, young men and older men, respectively, =19.9% (95% CI = 9.8%, 27.9%), 48.9% (46.6%, 50.8%), 46.2% (38.5%, 52.5%), 64.3% (62.2%, 66.4%); AFs for drinking = 5.3% (-11.2%, 18.0%), 20.0% (14.5%, 25.0%), 21.5% (5.0%, 34.9%) and 50.4% (46.1%, 54.3%). A family history of early-onset cancer was associated with HNC risk in the young [OR = 2.27 (95% CI = 1.26, 4.10)], but not in the older adults [OR = 1.10 (0.91, 1.31)]. The attributable fraction for family history of early-onset cancer was 23.2% (8.60% to 31.4%) in young compared with 2.20% (-2 .41%, 5.80%) in older adults.
Conclusions: Differences in HNC aetiology according to age group may exist. The lower AF of cigarette smoking and alcohol drinking in young adults may be due to the reduced length of exposure due to the lower age. Other characteristics, such as those that are inherited, may play a more important role in HNC in young adults compared with older adults.
C1 [Toporcov, Tatiana Natasha; Antunes, Jose Leopoldo Ferreira; Wuensch Filho, Victor] Univ Sao Paulo, Fac Saude Publ, BR-01246904 Sao Paulo, SP, Brazil.
[Znaor, Ariana] Croatian Natl Canc Registry, Zagreb, Croatia.
[Zhang, Zuo-Feng] Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA.
[Yu, Guo-Pei] Peking Univ, Med Informat Ctr, Beijing 100871, Peoples R China.
[Yu, Guo-Pei] New York Med Coll, Valhalla, NY 10595 USA.
[Winn, Deborah M.; Purdue, Mark P.] NCI, Bethesda, MD 20892 USA.
[Wei, Qingyi; Sturgis, Erich M.] UT MD Anderson Canc Ctr, Houston, TX USA.
[Vilensky, Marta] Univ Buenos Aires, Inst Oncol Angel H Roffo, Buenos Aires, DF, Argentina.
[Vaughan, Thomas; Schwartz, Stephen M.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Thomson, Peter] Univ Newcastle, Sch Dent Sci, Newcastle Upon Tyne, Tyne & Wear, England.
[Talamini, Renato; Dal Maso, Luigino] Aviano Canc Ctr, I-33081 Aviano, Italy.
[Szeszenia-Dabrowska, Neonila] Inst Occupat Med, Lodz, Poland.
[Smith, Elaine] Univ Iowa, Coll Publ Hlth, Iowa City, IA USA.
[Shangina, Oxana] Russian Acad Med Sci, Canc Res Ctr, Moscow, Russia.
[Vaughan, Thomas; Schwartz, Stephen M.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Schantz, Stimson] New York Eye & Ear Infirm, New York, NY 10003 USA.
[Rudnai, Peter] Natl Inst Environm Hlth, Budapest, Hungary.
[Richiardi, Lorenzo] Univ Turin, Canc Epidemiol Unit, Dept Med Sci, Turin, Italy.
[Ramroth, Heribert] Heidelberg Univ, Inst Publ Hlth, Heidelberg, Germany.
[Olshan, Andrew F.] Univ N Carolina, Sch Publ Hlth, Chapel Hill, NC USA.
[Eluf-Neto, Jose] Univ Sao Paulo, Fac Med, Sao Paulo, Brazil.
[Muscat, Joshua] Penn State Coll Med, Hershey, PA USA.
[Moyses, Raquel Ajub] Univ Sao Paulo, Fac Med, Cirurgia Cabeca & Pescoco LIM 28, Sao Paulo, Brazil.
[Morgenstern, Hal] Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA.
[Morgenstern, Hal] Univ Michigan, Sch Publ Hlth, Dept Environm Hlth Sci, Ann Arbor, MI 48109 USA.
[Morgenstern, Hal] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA.
[Menezes, Ana] Univ Fed Pelotas, Pelotas, Brazil.
[McClean, Michael] Boston Univ, Sch Publ Hlth, Boston, MA USA.
[Matsuo, Keitaro] Aichi Canc Ctr, Res Inst, Nagoya, Aichi 464, Japan.
[Mates, Dana] Inst Publ Hlth, Bucharest, Romania.
[Macfarlane, Tatiana V.] Univ Aberdeen, Sch Dent, Aberdeen, Scotland.
[Lissowska, Jolanta] M Skasodowska Curie Mem Canc Ctr, Warsaw, Poland.
[Lissowska, Jolanta] Inst Oncol, Dept Canc Epidemiol & Prevent, Warsaw, Poland.
[Levi, Fabio] CHU Vaudois, IUMSP, CH-1011 Lausanne, Switzerland.
[Levi, Fabio] Univ Lausanne, Lausanne, Switzerland.
[Lazarus, Philip] Washington State Univ, Coll Pharm, Spokane, WA USA.
[La Vecchia, Carlo] Ist Ric Farmacol Mario Negri, IRCCS, Milan, Italy.
[La Vecchia, Carlo] Univ Milan, Dept Clin Sci & Community Hlth, Milan, Italy.
[Lagiou, Pagona] Univ Athens, Sch Med, GR-11527 Athens, Greece.
[Koifman, Sergio] Fundacao Osvvaldo Cruz, Escola Nacl Saude Publ, Rio De Janeiro, Brazil.
[Kjaerheim, Kristina] Canc Registry Norway, Oslo, Norway.
[Kelsey, Karl] Brown Univ, Dept Pathol & Lab Med, Providence, RI 02912 USA.
[Holcatova, Ivana] Charles Univ Prague, Fac Med 1, Prague, Czech Republic.
[Herrero, Rolando] WHO, Int Agcy Res Canc, Prevent & Implementat Grp, Lyon, France.
[Healy, Claire] Trinity Coll Sch Dent Sci, Dublin, Ireland.
[Hayes, Richard B.] NYU, Sch Med, Div Epidemiol, New York, NY USA.
[Franceschi, Silvia] Int Agcy Res Canc, F-69372 Lyon, France.
[Fernandez, Leticia] Inst Oncol & Radiobiol, Havana, Cuba.
[Fabianova, Eleonora] Reg Author Publ Hlth Banska Bystrica, Banska Bystrica, Slovakia.
[Daudt, Alexander W.; Brennan, Paul] Hosp Clin Porto Alegre, Porto Alegre, RS, Brazil.
[Curioni, Otavio Alberto] Secretaria Estado Saude Sao Paulo, Hosp Heliopolis, Sao Paulo, Brazil.
[Curado, Maria Paula] Int Prevent Res Inst, Lyon, France.
[Conway, David I.] Univ Glasgow, Sch Dent, Coll Med Vet & Life Sci, Glasgow, Lanark, Scotland.
[Castellsague, Xavier] CIBER ESP, IDIBELL, ICO, Barcelona, Spain.
[Canova, Cristina] Univ Padua, Padua, Italy.
[Cadoni, Gabriella] Univ Cattolica Sacro Cuore, Inst Otorhinolaryngol, Rome, Italy.
[Boccia, Stefania] Univ Cattolica Sacro Cuore, Inst Publ Hlth, Rome, Italy.
[Ahrens, Wolfgang] BIPS, Leibniz Inst Prevent Res & Epidemiol, Bremen, Germany.
[Ahrens, Wolfgang] Univ Bremen, Inst Stat, Fac Math & Comp Sci, D-28359 Bremen, Germany.
[Agudo, Antonio] IDIBELL, ICO, Barcelona, Spain.
[Boffetta, Paolo] Mt Sinai Sch Med, Tisch Canc Inst, New York, NY USA.
[Hashibe, Mia] Univ Utah, Sch Med, Huntsnnan Canc Inst, Salt Lake City, UT USA.
[Lee, Yuan-Chin Amy] Univ Utah, Sch Med, Dept Family & Prevent Med, Div Publ Hlth, Salt Lake City, UT 84112 USA.
RP Toporcov, TN (reprint author), Univ Sao Paulo, Fac Saude Publ, Dept Epidemiol, Av Dr Arnaldo 715, BR-01246904 Sao Paulo, SP, Brazil.
EM tati_toporcov@yahoo.com.br
RI Thomson, Peter/L-7719-2016; Antunes, Jose/F-6969-2010; McClean,
Michael/J-2934-2015; Castellsague Pique, Xavier/N-5795-2014;
Szeszenia-Dabrowska, Neonila/F-7190-2010; Moyses, Raquel/N-4376-2015;
Purdue, Mark/C-9228-2016; Eluf-Neto, Jose/B-2522-2009; Agudo,
Antonio/J-1805-2016; Toporcov, Tatiana /M-7729-2015; Menezes,
Ana/G-7266-2012; Curado, Maria Paula/M-6200-2013
OI Matsuo, Keitaro/0000-0003-1761-6314; Ahrens,
Wolfgang/0000-0003-3777-570X; mates, dana/0000-0002-6219-9807; dal maso,
luigino/0000-0001-6163-200X; Thomson, Peter/0000-0002-2007-7975;
Macfarlane, Tatiana/0000-0002-9392-0812; richiardi,
lorenzo/0000-0003-0316-9402; La Vecchia, Carlo/0000-0003-1441-897X;
Kjaerheim, Kristina/0000-0003-0691-3735; Hayes,
Richard/0000-0002-0918-661X; Healy, Claire M/0000-0001-7940-4611;
Antunes, Jose/0000-0003-3972-9723; Castellsague Pique,
Xavier/0000-0002-0802-3595; Purdue, Mark/0000-0003-1177-3108; Eluf-Neto,
Jose/0000-0001-7504-2115; Curado, Maria Paula/0000-0001-8172-2483
FU US National Institutes of Health; National Cancer Institute
[R03CA113157]; National Institute of Dental and Craniofacial Health
[R03DE016611]; Italian Association for Research on Cancer (AIRC);
Italian League Against Cancer; Italian Ministry of Research; Swiss
League against Cancer [KFS1069-09-2000]; Fribourg League against Cancer
[FOR381.88]; Swiss Cancer Research [AKT 617]; Gustave-Roussy Institute
[88D28]; Swiss League against Cancer; Swiss Research against
Cancer/Oncosuisse [KFS-700, OCS-1633]; World Cancer Research Fund;
European Commission INCO-COPERNICUS Program [IC15-CT98-0332]; National
Institutes of Health (NIH) US [P01CA068384 K07CA104231, R01CA078609,
R01CA100679]; NIH [R01CA048996, R01DE012609, NIDCR R01DE11979, NIDCR
R01DE13110, NIH FIRCA TW01500, R01CA61188, P01CA068384, K07CA104231,
R01DE13158, P50CA90388, R01DA11386, R03CA77954, T32CA09142, U01CA96134,
R21ES011667, R01ES11740, R01CA100264, R01CA51845, R01CA30022]; Veterans
Affairs Merit Review Funds; National Institute of Environmental Health
Sciences [P30ES010126]; Alper Research Program for Environmental
Genomics of the UCLA Jonsson Comprehensive Cancer Center; National
Institutes of Health (NCI) US; NIDCR intramural programmes; Fondo para
la Investigacion Cientifica y Tecnologica (FONCYT) Argentina; IMIM
(Barcelona); Fundacao de Amparo a Pesquisa no Estado de Sao Paulo
(FAPESP) [01/01768-2]; European Commission [IC18-CT97-0222]; IARC
multicentre study: Fondo de Investigaciones Sanitarias (FIS) of the
Spanish Government [FIS 97/0024, FIS 97/0662, BAE 01/5013];
International Union Against Cancer (UICC); Yamagiwa-Yoshida Memorial
International Cancer Study Grant; AIRC (Italian Agency for Research on
Cancer) [10068]; US multicentre study: the Intramural Program of the
NCI, NIH, United States; Sao Paulo study: Fundacao de Amparo a Pesquisa
no Estado de Sao Paulo (FAPESP) [04/12054-9, 10/51168-0]; European
Community [QLK1-CT-2001-00182]; German Ministry of Education and
Research [01GB9702/3]; Ministry of Education, Science, Sports, Culture
and Technology of Japan [17015052]; Ministry of Health, Labour and
Welfare of Japan [H20-002]
FX This work was supported by the US National Institutes of Health, the
National Cancer Institute [R03CA113157] and the National Institute of
Dental and Craniofacial Health [R03DE016611]. The individual studies
were funded by the following grants: Milan study: Italian Association
for Research on Cancer (AIRC); Aviano study: Italian Association for
Research on Cancer (AIRC), Italian League Against Cancer and Italian
Ministry of Research; France study: Swiss League against Cancer
[KFS1069-09-2000], Fribourg League against Cancer [FOR381.88], Swiss
Cancer Research [AKT 617] and Gustave-Roussy Institute [88D28]; Italy
multicentre study: Italian Association for Research on Cancer (AIRC),
Italian League against Cancer and Italian Ministry of Research; Swiss
study: Swiss League against Cancer and the Swiss Research against
Cancer/Oncosuisse [KFS-700, OCS-1633]; Central Europe study: World
Cancer Research Fund and the European Commission INCO-COPERNICUS Program
[Contract No. IC15-CT98-0332]; New York study: National Institutes of
Health (NIH) US [P01CA068384 K07CA104231]; Seattle study: NIH
[R01CA048996, R01DE012609]; Iowa study: NIH [NIDCR R01DE11979, NIDCR
R01DE13110, NIH FIRCA TW01500] and Veterans Affairs Merit Review Funds;
North Carolina study: NIH [R01CA61188] and in part by a grant from the
National Institute of Environmental Health Sciences [P30ES010126]; Tampa
study: NIH [P01CA068384, K07CA104231, R01DE13158]; Los Angeles study:
NIH [P50CA90388, R01DA11386, R03CA77954, T32CA09142, U01CA96134,
R21ES011667] and the Alper Research Program for Environmental Genomics
of the UCLA Jonsson Comprehensive Cancer Center; Houston study: NIH
[R01ES11740, R01CA100264]; Puerto Rico study: jointly funded by National
Institutes of Health (NCI) US and NIDCR intramural programmes; Latin
America study: Fondo para la Investigacion Cientifica y Tecnologica
(FONCYT) Argentina, IMIM (Barcelona), Fundacao de Amparo a Pesquisa no
Estado de Sao Paulo (FAPESP) [No 01/01768-2] and European Commission
[IC18-CT97-0222]; IARC multicentre study: Fondo de Investigaciones
Sanitarias (FIS) of the Spanish Government [FIS 97/0024, FIS 97/0662,
BAE 01/5013], International Union Against Cancer (UICC) and
Yamagiwa-Yoshida Memorial International Cancer Study Grant; Boston
study: National Institutes of Health (NIH) US [R01CA078609,
R01CA100679]; Rome study: AIRC (Italian Agency for Research on Cancer)
[10068]; US multicentre study: the Intramural Program of the NCI, NIH,
United States; Sao Paulo study: Fundacao de Amparo a Pesquisa no Estado
de Sao Paulo (FAPESP) [04/12054-9, 10/51168-0]; MSKCC study: NIH
[R01CA51845]; Seattle study: NIH [R01CA30022]; European study: European
Community (5th Framework Programme) [QLK1-CT-2001-00182];
Germany-Heidelberg study: German Ministry of Education and Research
[01GB9702/3]; Japan study: Scientific Research grant from the Ministry
of Education, Science, Sports, Culture and Technology of Japan
[17015052] and a grant for the Third-Term Comprehensive 10-Year Strategy
for Cancer Control from the Ministry of Health, Labour and Welfare of
Japan [H20-002].
NR 75
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PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0300-5771
EI 1464-3685
J9 INT J EPIDEMIOL
JI Int. J. Epidemiol.
PD FEB
PY 2015
VL 44
IS 1
BP 169
EP 185
DI 10.1093/ije/dyu255
PG 17
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA CD1WC
UT WOS:000350864200024
PM 25613428
ER
PT J
AU Geng, EH
Neilands, TB
Thiebaut, R
Bwana, MB
Nash, D
Moore, RD
Wood, R
Zannou, DM
Althoff, KN
Lim, PL
Nachega, JB
Easterbrook, PJ
Kambugu, A
Little, F
Nakigozi, G
Nakanjako, D
Kiggundu, V
Li, PCK
Bangsberg, DR
Fox, MP
Prozesky, HW
Hunt, PW
Davies, MA
Reynolds, SJ
Egger, M
Yiannoutsos, CT
Vittinghoff, EV
Deeks, SG
Martin, JN
AF Geng, Elvin H.
Neilands, Torsten B.
Thiebaut, Rodolphe
Bwana, Mwebesa Bosco
Nash, Denis
Moore, Richard D.
Wood, Robin
Zannou, Djimon Marcel
Althoff, Keri N.
Lim, Poh Lian
Nachega, Jean B.
Easterbrook, Philippa J.
Kambugu, Andrew
Little, Francesca
Nakigozi, Gertrude
Nakanjako, Damalie
Kiggundu, Valerian
Li, Patrick Chung Ki
Bangsberg, David R.
Fox, Matthew P.
Prozesky, Hans W.
Hunt, Peter W.
Davies, Mary-Ann
Reynolds, Steven J.
Egger, Matthias
Yiannoutsos, Constantin T.
Vittinghoff, Eric V.
Deeks, Steven G.
Martin, Jeffrey N.
TI CD4+T cell recovery during suppression of HIV replication: an
international comparison of the immunological efficacy of antiretroviral
therapy in North America, Asia and Africa
SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE HIV; Africa; antiretroviral therapy; CD4+T cell counts; immunological
activation
ID SUBTYPE-D; INFECTED INDIVIDUALS; VIRAL SUPPRESSION; GENETIC SUBTYPES;
COUNT RECOVERY; UGANDA; REDISTRIBUTION; RECOMBINANTS; ACTIVATION;
INITIATION
AB Background: Even among HIV-infected patients who fully suppress plasma HIV RNA replication on antiretroviral therapy, genetic (e.g. CCL3L1 copy number), viral (e.g. tropism) and environmental (e.g. chronic exposure to microbial antigens) factors influence CD4 recovery. These factors differ markedly around the world and therefore the expected CD4 recovery during HIV RNA suppression may differ globally.
Methods: We evaluated HIV-infected adults from North America, West Africa, East Africa, Southern Africa and Asia starting non-nucleoside reverse transcriptase inhibitor-based regimens containing efavirenz or nevirapine, who achieved at least one HIV RNA level <500/mu l in the first year of therapy and observed CD4 changes during HIV RNA suppression. We used a piecewise linear regression to estimate the influence of region of residence on CD4 recovery, adjusting for socio-demographic and clinical characteristics. We observed 28 217 patients from 105 cohorts over 37 825 person-years.
Results: After adjustment, patients from East Africa showed diminished CD4 recovery as compared with other regions. Three years after antiretroviral therapy initiation, the mean CD4 count for a prototypical patient with a pre-therapy CD4 count of 150 mu l was 529/mu l [95% confidence interval (Cl): 517-541] in North America, 494/mu l (95% Cl: 429-559) in West Africa, 5150 (95% Cl: 508-522) in Southern Africa, 503/mu l (95% Cl: 478-528) in Asia and 437/mu l (95% Cl: 425-449) in East Africa.
Conclusions: CD4 recovery during HIV RNA suppression is diminished in East Africa as compared with other regions of the world, and observed differences are large enough to potentially influence clinical outcomes. Epidemiological analyses on a global scale can identify macroscopic effects unobservable at the clinical, national or individual regional level.
C1 [Geng, Elvin H.; Neilands, Torsten B.; Hunt, Peter W.; Vittinghoff, Eric V.; Deeks, Steven G.; Martin, Jeffrey N.] Univ Calif San Francisco, San Francisco, CA 94110 USA.
[Thiebaut, Rodolphe] Bordeaux Univ, INSERM, U897, Bordeaux, France.
[Bwana, Mwebesa Bosco] Mbarara Univ Sci & Technol, Mbarara, Uganda.
[Nash, Denis] CUNY, New York, NY 10021 USA.
[Moore, Richard D.; Althoff, Keri N.; Reynolds, Steven J.] Johns Hopkins Univ, Baltimore, MD USA.
[Wood, Robin; Little, Francesca; Davies, Mary-Ann] Univ Cape Town, ZA-7925 Cape Town, South Africa.
[Zannou, Djimon Marcel] Ctr Natl Hosp Univ, Cotonou, Benin.
[Lim, Poh Lian] Tan Tock Seng Hosp, Inst Infect Dis, Singapore, Singapore.
[Nachega, Jean B.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Program Infect Dis, Pittsburgh, PA USA.
[Nachega, Jean B.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Nachega, Jean B.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Int Hlth, Baltimore, MD USA.
[Nachega, Jean B.] Univ Stellenbosch, Dept Med, Cape Town, South Africa.
[Nachega, Jean B.] Univ Stellenbosch, Ctr Infect Dis, Cape Town, South Africa.
[Easterbrook, Philippa J.; Kambugu, Andrew; Nakanjako, Damalie] Infect Dis Inst, Kampala, Uganda.
[Nakigozi, Gertrude; Kiggundu, Valerian; Reynolds, Steven J.] Rakai Hlth Sci Program, Kalisizo, Uganda.
[Li, Patrick Chung Ki] Queen Elizabeth Hosp, Hong Kong, Hong Kong, Peoples R China.
[Bangsberg, David R.] Harvard Univ, Massachusetts Gen Hosp, Ctr Global Hlth, Boston, MA 02115 USA.
[Fox, Matthew P.] Boston Univ, Ctr Global Hlth & Dev, Boston, MA 02215 USA.
[Fox, Matthew P.] Univ Witwatersrand, Fac Hlth Sci, Sch Clin Med, Hlth Econ & Epidemiol Res Off,Dept Internal Med, Johannesburg, South Africa.
[Prozesky, Hans W.] Univ Stellenbosch, Dept Med, Div Infect Dis, Cape Town, South Africa.
[Prozesky, Hans W.] Tygerberg Acad Hosp, Cape Town, South Africa.
[Reynolds, Steven J.] NIAID, Washington, DC USA.
[Egger, Matthias] Univ Bern, Bern, Switzerland.
[Yiannoutsos, Constantin T.] Indiana Univ, Indianapolis, IN 46204 USA.
RP Geng, EH (reprint author), Univ Calif San Francisco, San Francisco Gen Hosp, Div HIV AIDS, 995 Potrero Ave,Bldg 80,Box 0874, San Francisco, CA 94110 USA.
EM genge@php.ucsf.edu
OI Prozesky, Hans/0000-0001-9715-3449
FU National Institutes of Health [K23 AI084544, U01 AI069918, U01 AI069919,
U01 AI069924, U01 AI069911, U01 AI069907, R01 MH054907, P30 AI027763];
Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, National Institutes of Health
FX Funding has been provided by the National Institutes of Health [K23
AI084544, U01 AI069918, U01 AI069919, U01 AI069924, U01 AI069911, U01
AI069907, R01 MH054907 and P30 AI027763] and the Division of Intramural
Research, National Institute of Allergy and Infectious Diseases,
National Institutes of Health.
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U1 0
U2 4
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0300-5771
EI 1464-3685
J9 INT J EPIDEMIOL
JI Int. J. Epidemiol.
PD FEB
PY 2015
VL 44
IS 1
BP 251
EP 263
DI 10.1093/ije/dyu271
PG 13
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA CD1WC
UT WOS:000350864200033
PM 25859596
ER
PT J
AU Maeda, S
Zempo-Miyaki, A
Sasai, H
Tsujimoto, T
So, R
Tanaka, K
AF Maeda, Seiji
Zempo-Miyaki, Asako
Sasai, Hiroyuki
Tsujimoto, Takehiko
So, Rina
Tanaka, Kiyoji
TI Lifestyle Modification Decreases Arterial Stiffness in Overweight and
Obese Men: Dietary Modification vs. Exercise Training
SO INTERNATIONAL JOURNAL OF SPORT NUTRITION AND EXERCISE METABOLISM
LA English
DT Article
DE diet; exercise; obesity; endothelin-1; nitric oxide
ID PULSE-WAVE VELOCITY; NITRIC-OXIDE; POSTMENOPAUSAL WOMEN; ENDOTHELIAL
FUNCTION; AEROBIC EXERCISE; ADIPOSE-TISSUE; IN-VIVO; REGULAR EXERCISE;
BODY-WEIGHT; ADIPONECTIN
AB Obesity and increased arterial stiffness are independent risk factors for cardiovascular disease. Arterial stiffness is increased in obese individuals than in age-matched nonobese individuals. We demonstrated that dietary modification and exercise training are effective in reducing arterial stiffness in obese persons. However, the differences in the effect on arterial stiffness between dietary modification and exercise training are unknown. The purpose of the current study was to compare the effect of dietary modification and aerobic exercise training on arterial stiffness and endothelial function in overweight and obese persons. Forty-five overweight and obese men (48 +/- 1 year) completed either a dietary modification (well-balanced nutrient, 1680 kcal/day) or an exercise-training program (walking, 40-60 min/day, 3 days/week) for 12 weeks. Before and after the intervention, all participants underwent anthropometric measurements. Arterial stiffness was measured based on carotid arterial compliance, brachial-ankle pulse wave velocity (baPWV), and endothelial function was determined by circulating level of endothelin-1 (ET-1) and nitric oxide metabolite (nitrites/nitrate as metabolite: NOx). Body mass and waist circumference significantly decreased after both intervention programs. Weight loss was greater after dietary modification than after exercise training (-10.1 +/- 0.6 kg vs. -3.6 +/- 0.5 kg, p < .01). Although arterial stiffness and the plasma levels of ET-1 and NOx were improved after dietary modification or exercise training, there were no differences in those improvements between the 2 types of interventions. Exercise training improves arterial function in obese men without as much weight loss as after dietary modification.
C1 [Maeda, Seiji; Tsujimoto, Takehiko; So, Rina; Tanaka, Kiyoji] Univ Tsukuba, Fac Hlth & Sport Sci, Tsukuba, Ibaraki, Japan.
[Zempo-Miyaki, Asako] Univ Tsukuba, Fac Med, Tsukuba, Ibaraki, Japan.
[Sasai, Hiroyuki] NIH, Bethesda, MD 20892 USA.
RP Maeda, S (reprint author), Univ Tsukuba, Fac Hlth & Sport Sci, Tsukuba, Ibaraki, Japan.
EM maeda@taiiku.tsukuba.ac.jp
OI Sasai, Hiroyuki/0000-0001-8120-6163
FU Ministry of Education, Culture, Sports, Science and Technology of Japan
[18300215]
FX This work was supported by Grants-in-Aid for Scientific Research from
the Ministry of Education, Culture, Sports, Science and Technology of
Japan (18300215).
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PU HUMAN KINETICS PUBL INC
PI CHAMPAIGN
PA 1607 N MARKET ST, PO BOX 5076, CHAMPAIGN, IL 61820-2200 USA
SN 1526-484X
EI 1543-2742
J9 INT J SPORT NUTR EXE
JI Int. J. Sport Nutr. Exerc. Metab.
PD FEB
PY 2015
VL 25
IS 1
BP 69
EP 77
DI 10.1123/ijsnem.2013-0107
PG 9
WC Nutrition & Dietetics; Sport Sciences
SC Nutrition & Dietetics; Sport Sciences
GA CD0PS
UT WOS:000350777000009
PM 25029200
ER
PT J
AU Logan, JG
Engler, MB
Kim, H
AF Logan, Jeongok G.
Engler, Mary B.
Kim, Hyungsuk
TI Genetic Determinants of Arterial Stiffness
SO JOURNAL OF CARDIOVASCULAR TRANSLATIONAL RESEARCH
LA English
DT Article
DE Arterial stiffness; Arteriosclerosis; Atherosclerosis; Genotype;
Hypertension
ID PULSE-WAVE VELOCITY; II TYPE-1 RECEPTOR; ANGIOTENSIN-CONVERTING ENZYME;
SMOOTH-MUSCLE-CELLS; LAMIN A/C GENE; AORTIC STIFFNESS; HYPERTENSIVE
PATIENTS; BLOOD-PRESSURE; NITRIC-OXIDE; CARDIOVASCULAR-DISEASE
AB Stiffness of large arteries (called arteriosclerosis) is an independent predictor of cardiovascular morbidity and mortality. Although previous studies have shown that arterial stiffness is moderately heritable, genetic factors contributing to arterial stiffness are largely unknown. In this paper, we reviewed the available literature on genetic variants that are potentially related to arterial stiffness. Most variants have shown mixed depictions of their association with arterial stiffness across multiple studies. Various methods to measure arterial stiffness at different arterial sites can contribute to these inconsistent results. In addition, studies in patient populations with hypertension or atherosclerosis may overestimate the impact of genetic variants on arterial stiffness. Future studies are recommended to standardize current measures of arterial stiffness in different age groups. Studies conducted in normal healthy subjects may also provide better opportunities to find novel genetic variants of arterial stiffness.
C1 [Logan, Jeongok G.] Univ Virginia, Sch Nursing, Charlottesville, VA 22903 USA.
[Engler, Mary B.; Kim, Hyungsuk] NINR, NIH, Div Intramural Res, Bethesda, MD 20892 USA.
RP Logan, JG (reprint author), Univ Virginia, Sch Nursing, 225 Jeanette Lancaster Way, Charlottesville, VA 22903 USA.
EM jl3zj@virginia.edu; englermb@mail.nih.gov; kimhy@mail.nih.gov
NR 149
TC 0
Z9 0
U1 4
U2 7
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1937-5387
EI 1937-5395
J9 J CARDIOVASC TRANSL
JI J. Cardiovasc. Transl. Res.
PD FEB
PY 2015
VL 8
IS 1
BP 23
EP 43
DI 10.1007/s12265-014-9597-x
PG 21
WC Cardiac & Cardiovascular Systems; Medicine, Research & Experimental
SC Cardiovascular System & Cardiology; Research & Experimental Medicine
GA CD1AJ
UT WOS:000350805700003
PM 25472935
ER
PT J
AU Dhalla, F
Murray, S
Sadler, R
Chaigne-Delalande, B
Sadaoka, T
Soilleux, E
Uzel, G
Miller, J
Collins, GP
Hatton, CSR
Bhole, M
Ferry, B
Chapel, HM
Cohen, JI
Patel, SY
AF Dhalla, Fatima
Murray, Sarah
Sadler, Ross
Chaigne-Delalande, Benjamin
Sadaoka, Tomohiko
Soilleux, Elizabeth
Uzel, Gulbu
Miller, Joanne
Collins, Graham Peter
Hatton, Christian Simon Ross
Bhole, Malini
Ferry, Berne
Chapel, Helen M.
Cohen, Jeffrey I.
Patel, Smita Y.
TI Identification of a Novel Mutation in MAGT1 and Progressive Multifocal
Leucoencephalopathy in a 58-Year-Old Man with XMEN Disease
SO JOURNAL OF CLINICAL IMMUNOLOGY
LA English
DT Article
DE XMEN Disease; MAGT1; Epstein-Barr virus (EBV); progressive multifocal
leucoencephalopathy (PML)
ID CD4(+) T-LYMPHOCYTOPENIA; JC VIRUS; BONE-MARROW; CELLS; PATHOGENESIS;
INFECTION; PATIENT
AB XMEN disease (X-linked immunodeficiency with Magnesium defect, Epstein-Barr virus infection and Neoplasia) is a novel primary immune deficiency caused by mutations in MAGT1 and characterised by chronic infection with Epstein-Barr virus (EBV), EBV-driven lymphoma, CD4 T-cell lymphopenia, and dysgammaglobulinemia [1]. Functional studies have demonstrated roles for magnesium as a second messenger in T-cell receptor signalling [1], and for NKG2D expression and consequently NK- and CD8 T-cell cytotoxicity [2]. 7 patients have been described in the literature; the oldest died at 45 years and was diagnosed posthumously [1-3]. We present the case of a 58-year-old Caucasian gentleman with a novel mutation in MAGT1 with the aim of adding to the phenotype of this newly described disease by detailing his clinical course over more than 20 years.
C1 [Dhalla, Fatima; Miller, Joanne; Chapel, Helen M.; Patel, Smita Y.] Univ Oxford, Nuffield Dept Med, Oxford, England.
[Dhalla, Fatima; Murray, Sarah; Miller, Joanne; Chapel, Helen M.; Patel, Smita Y.] John Radcliffe Hosp, Dept Clin Immunol, Oxford OX3 9DU, England.
[Sadler, Ross; Ferry, Berne] Churchill Hosp, Dept Clin Lab Immunol, Oxford OX3 7LJ, England.
[Chaigne-Delalande, Benjamin] NIAID, Mol Dev Sect, Lymphocyte Mol Genet Unit, Lab Immunol,NIH, Bethesda, MD 20892 USA.
[Sadaoka, Tomohiko; Cohen, Jeffrey I.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
[Soilleux, Elizabeth] Univ Oxford, Nuffield Dept Clin Lab Sci, Oxford, England.
[Uzel, Gulbu] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
[Collins, Graham Peter; Hatton, Christian Simon Ross] Churchill Hosp, Dept Hematol, Oxford OX3 7LJ, England.
[Bhole, Malini] Russells Hall Hosp, Dept Clin Immunol, Dudley, W Midlands, England.
RP Dhalla, F (reprint author), John Radcliffe Hosp, Dept Clin Immunol, Oxford OX3 9DU, England.
EM fatima.dhalla@doctors.org.uk
OI sadaoka, tomohiko/0000-0001-7951-6904
FU Intramural NIH HHS
NR 14
TC 7
Z9 7
U1 0
U2 4
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0271-9142
EI 1573-2592
J9 J CLIN IMMUNOL
JI J. Clin. Immunol.
PD FEB
PY 2015
VL 35
IS 2
BP 112
EP 118
DI 10.1007/s10875-014-0116-2
PG 7
WC Immunology
SC Immunology
GA CD2EE
UT WOS:000350886300005
PM 25504528
ER
PT J
AU Buchbinder, D
Baker, R
Lee, YN
Ravell, J
Zhang, Y
McElwee, J
Nugent, D
Coonrod, EM
Durtschi, JD
Augustine, NH
Voelkerding, KV
Csomos, K
Rosen, L
Browne, S
Walter, JE
Notarangelo, LD
Hill, HR
Kumanovics, A
AF Buchbinder, David
Baker, Rebecca
Lee, Yu Nee
Ravell, Juan
Zhang, Yu
McElwee, Joshua
Nugent, Diane
Coonrod, Emily M.
Durtschi, Jacob D.
Augustine, Nancy H.
Voelkerding, Karl V.
Csomos, Krisztian
Rosen, Lindsey
Browne, Sarah
Walter, Jolan E.
Notarangelo, Luigi D.
Hill, Harry R.
Kumanovics, Attila
TI Identification of Patients with RAG Mutations Previously Diagnosed with
Common Variable Immunodeficiency Disorders
SO JOURNAL OF CLINICAL IMMUNOLOGY
LA English
DT Article
DE RAG1; RAG deficiency; primary immunodeficiency; severe combined immune
deficiency; common variable immunodeficiency disorder; exome sequencing;
gene panel
ID GRANULOMATOUS-DISEASE; AUTOIMMUNITY; DEFICIENCY; LYMPHOPENIA; CELLS
AB Combined immunodeficiency (CID) presents a unique challenge to clinicians. Two patients presented with the prior clinical diagnosis of common variable immunodeficiency (CVID) disorder marked by an early age of presentation, opportunistic infections, and persistent lymphopenia. Due to the presence of atypical clinical features, next generation sequencing was applied documenting RAG deficiency in both patients.
Two different genetic analysis techniques were applied in these patients including whole exome sequencing in one patient and the use of a gene panel designed to target genes known to cause primary immunodeficiency disorders (PIDD) in a second patient. Sanger dideoxy sequencing was used to confirm RAG1 mutations in both patients.
Two young adults with a history of recurrent bacterial sinopulmonary infections, viral infections, and autoimmune disease as well as progressive hypogammaglobulinemia, abnormal antibody responses, lymphopenia and a prior diagnosis of CVID disorder were evaluated. Compound heterozygous mutations in RAG1 (1) c256_257delAA, p86VfsX32 and (2) c1835A > G, pH612R were documented in one patient. Compound heterozygous mutations in RAG1 (1) c.1566G > T, p.W522C and (2) c.2689C > T, p. R897X) were documented in a second patient post-mortem following a fatal opportunistic infection.
Astute clinical judgment in the evaluation of patients with PIDD is necessary. Atypical clinical findings such as early onset, granulomatous disease, or opportunistic infections should support the consideration of atypical forms of late onset CID secondary to RAG deficiency. Next generation sequencing approaches provide powerful tools in the investigation of these patients and may expedite definitive treatments.
C1 [Buchbinder, David; Nugent, Diane] UC Irvine, CHOC Childrens Hosp, Pediat Hematol, Orange, CA USA.
[Baker, Rebecca; Ravell, Juan; Rosen, Lindsey; Browne, Sarah] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
[Lee, Yu Nee] Harvard Univ, Sch Med, Boston Childrens Hosp, Div Immunol, Boston, MA USA.
[Zhang, Yu] NIAID, Lab Host Defenses, NIH, Bethesda, MD 20892 USA.
[McElwee, Joshua] Merck & Co Inc, Merck Res Labs, Boston, MA USA.
[Walter, Jolan E.; Notarangelo, Luigi D.] Boston Childrens Hosp, Div Immunol, Boston, MA USA.
[Coonrod, Emily M.; Durtschi, Jacob D.; Augustine, Nancy H.; Voelkerding, Karl V.; Hill, Harry R.; Kumanovics, Attila] ARUP Inst Clin & Expt Pathol, Salt Lake City, UT USA.
[Augustine, Nancy H.; Voelkerding, Karl V.; Hill, Harry R.; Kumanovics, Attila] Univ Utah, Sch Med, Dept Pathol, Salt Lake City, UT USA.
[Hill, Harry R.] Univ Utah, Sch Med, Dept Internal Med, Salt Lake City, UT USA.
[Hill, Harry R.] Univ Utah, Sch Med, Dept Pediat, Salt Lake City, UT USA.
[Csomos, Krisztian; Walter, Jolan E.] Harvard Univ, Sch Med, Pediat Allergy & Immunol, Boston, MA USA.
[Csomos, Krisztian; Walter, Jolan E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Immunol & Inflammatory Dis, Boston, MA USA.
[Buchbinder, David] CHOC Childrens Hosp, Div Hematol, Orange, CA 92868 USA.
RP Buchbinder, D (reprint author), CHOC Childrens Hosp, Div Hematol, 1201 La Veta, Orange, CA 92868 USA.
EM dbuchbinder@choc.org
RI Notarangelo, Luigi/F-9718-2016
OI Notarangelo, Luigi/0000-0002-8335-0262
FU Intramural NIH HHS; NIAID NIH HHS [1K08AI103035-03, 5P01AI076210-04, K08
AI103035, P01 AI076210, U54 AI082973, U54AI082973]
NR 22
TC 15
Z9 15
U1 0
U2 4
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0271-9142
EI 1573-2592
J9 J CLIN IMMUNOL
JI J. Clin. Immunol.
PD FEB
PY 2015
VL 35
IS 2
BP 119
EP 124
DI 10.1007/s10875-014-0121-5
PG 6
WC Immunology
SC Immunology
GA CD2EE
UT WOS:000350886300006
PM 25516070
ER
PT J
AU Strollo, SE
Caserotti, P
Ward, RE
Glynn, NW
Goodpaster, BH
Strotmeyer, ES
AF Strollo, S. E.
Caserotti, P.
Ward, R. E.
Glynn, N. W.
Goodpaster, B. H.
Strotmeyer, E. S.
TI A review of the relationship between leg power and selected chronic
disease in older adults
SO JOURNAL OF NUTRITION HEALTH & AGING
LA English
DT Article
DE Leg power; older adults; chronic disease; aging; muscle power
ID NUTRITION EXAMINATION SURVEY; PERIPHERAL ARTERIAL-DISEASE; EXAMINATION
SURVEY NHANES; MUSCLE POWER; SKELETAL-MUSCLE; BODY-COMPOSITION;
HEART-FAILURE; GAIT SPEED; QUADRICEPS STRENGTH; KNEE OSTEOARTHRITIS
AB This review investigates the relationship between leg muscle power and the chronic conditions of osteoarthritis, diabetes mellitus, and cardiovascular disease among older adults. Current literature assessing the impact of chronic disease on leg power has not yet been comprehensively characterized. Importantly, individuals with these conditions have shown improved leg power with training.
A search was performed using PubMed to identify original studies published in English from January 1998 to August 2013. Leg power studies, among older adults a parts per thousand yen 50 years of age, which assessed associations with osteoarthritis, diabetes mellitus, and/or cardiovascular disease were selected. Studies concerning post-surgery rehabilitation, case studies, and articles that did not measure primary results were excluded.
Sixteen studies met inclusion criteria, addressing osteoarthritis (n=5), diabetes mellitus (n=5), and cardiovascular disease (n=6). Studies generally supported associations of lower leg power among older adults with chronic disease, although small sample sizes, cross-sectional data, homogenous populations, varied disease definitions, and inconsistent leg power methods limited conclusions.
Studies suggest that osteoarthritis, diabetes mellitus, and cardiovascular disease are associated with lower leg power compared to older adults without these conditions. These studies are limited, however, by the heterogeneity in study populations and a lack of standardized measurements of leg power. Future larger studies of more diverse older adults with well-defined chronic disease using standard measures of leg power and interventions to improve leg power in these older adults with chronic disease are needed.
C1 [Strollo, S. E.] NIAID, NIH, Bethesda, MD 20892 USA.
[Caserotti, P.] Univ Southern Denmark, Dept Sports Sci & Clin Biomech, Odense, Denmark.
[Ward, R. E.] Boston Univ, Hlth & Disabil Res Inst, Spaulding Rehabil Hosp, Boston, MA 02215 USA.
[Glynn, N. W.; Strotmeyer, E. S.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15213 USA.
[Goodpaster, B. H.] Sanford Burnham Med Res Inst, Orlando, FL USA.
RP Strotmeyer, ES (reprint author), Univ Pittsburgh, Dept Epidemiol, 130 North Bellefield Ave,Room 515, Pittsburgh, PA 15213 USA.
EM sara.strollo@nih.gov; pcaserotti@health.sdu.dk; rew27@bu.edu;
glynnn@edc.pitt.edu; bgoodpaster@sanfordburnham.org;
strotmeyere@edc.pitt.edu
OI Strotmeyer, Elsa/0000-0002-4093-6036; Glynn, Nancy/0000-0003-2265-0162
FU Pittsburgh Claude D. Pepper Older Americans Independence Center;
Research Registry, and Developmental Pilot Grant [NIH P30 AG024826, NIH
P30 AG024827]; National Institute on Aging Professional Services
[HHSN271201100605P]; NIA Aging Training Grant [T32 AG000181]; Intramural
Research Program of the National Institute on Aging
FX This work was supported by the Pittsburgh Claude D. Pepper Older
Americans Independence Center, Research Registry, and Developmental
Pilot Grant - NIH P30 AG024826 and NIH P30 AG024827; National Institute
on Aging Professional Services Contract HHSN271201100605P; NIA Aging
Training Grant T32 AG000181; and by the Intramural Research Program of
the National Institute on Aging.
NR 81
TC 2
Z9 2
U1 0
U2 2
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 FEB
PY 2015
VL 19
IS 2
BP 240
EP 248
DI 10.1007/s12603-014-0528-y
PG 9
WC Geriatrics & Gerontology; Nutrition & Dietetics
SC Geriatrics & Gerontology; Nutrition & Dietetics
GA CC4DH
UT WOS:000350300500018
PM 25651453
ER
PT J
AU Torchia, DA
AF Torchia, Dennis A.
TI NMR studies of dynamic biomolecular conformational ensembles
SO PROGRESS IN NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY
LA English
DT Review
DE Spin; Relaxation; Residual dipolar coupling; Order parameter; Dynamics
ID NUCLEAR-MAGNETIC-RESONANCE; SOLID-STATE NMR; RESIDUAL DIPOLAR COUPLINGS;
CHEMICAL-SHIFT ANISOTROPY; LIQUID-CRYSTALLINE PHASE; MODEL-FREE
APPROACH; PARAMAGNETIC RELAXATION ENHANCEMENT; PROTEIN-STRUCTURE
DETERMINATION; PANCREATIC TRYPSIN-INHIBITOR; NONRIGID ROTATIONAL MOTION
AB Multidimensional heteronuclear NMR approaches can provide nearly complete sequential signal assignments of isotopically enriched biomolecules. The availability of assignments together with measurements of spin relaxation rates, residual spin interactions, J-couplings and chemical shifts provides information at atomic resolution about internal dynamics on timescales ranging from ps to ms, both in solution and in the solid state. However, due to the complexity of biomolecules, it is not possible to extract a unique atomic-resolution description of biomolecular motions even from extensive NMR data when many conformations are sampled on multiple timescales. For this reason, powerful computational approaches are increasingly applied to large NMR data sets to elucidate conformational ensembles sampled by biomolecules. In the past decade, considerable attention has been directed at an important class of biomolecules that function by binding to a wide variety of target molecules. Questions of current interest are: "Does the free biomolecule sample a conformational ensemble that encompasses the conformations found when it binds to various targets; and if so, on what time scale is the ensemble sampled?" This article reviews recent efforts to answer these questions, with a focus on comparing ensembles obtained for the same biomolecules by different investigators. A detailed comparison of results obtained is provided for three biomolecules: ubiquitin, calmodulin and the HIV-1 trans-activation response RNA. Published by Elsevier B.V.
C1 NIH, Bethesda, MD 20892 USA.
RP Torchia, DA (reprint author), NIH, 5 Mem Dr, Bethesda, MD 20892 USA.
EM dtorchia@dir.nidcr.nih.gov
FU NIH Intramural Research Program of the NIDCR; NIH Intramural Research
Program of the NIDDK
FX I thank Ad Bax, Marius Clore, Attila Szabo, Rob Tycko and Jinfa Ying for
numerous helpful suggestions. This work was supported by the NIH
Intramural Research Programs of the NIDCR and NIDDK.
NR 173
TC 11
Z9 11
U1 12
U2 75
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0079-6565
J9 PROG NUCL MAG RES SP
JI Prog. Nucl. Magn. Reson. Spectrosc.
PD FEB
PY 2015
VL 84
BP 14
EP 32
DI 10.1016/j.pnmrs.2014.11.001
PG 19
WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical; Spectroscopy
SC Chemistry; Physics; Spectroscopy
GA CD8CJ
UT WOS:000351322500002
PM 25669739
ER
PT J
AU Yang, QC
Sun, X
Wang, YM
Wu, Q
Feng, J
Chen, BY
AF Yang, Qing-chan
Sun, Xin
Wang, Yong-mei
Wu, Qi
Feng, Jing
Chen, Bao-yuan
TI Systematic and Endothelial Inflammation and Endothelial Progenitor Cell
Levels in Emphysematous Rats Exposed to Intermittent Hypoxia
SO RESPIRATORY CARE
LA English
DT Article
DE intermittent hypoxia; emphysema; inflammation; endothelial dysfunction;
endothelial progenitor cell
ID OBSTRUCTIVE SLEEP-APNEA; INTIMA-MEDIA THICKNESS; PULMONARY-DISEASE;
OVERLAP SYNDROME; LUNG-DISEASE; ATHEROSCLEROSIS; HYPERTENSION;
MONOCYTES; ALPHA; COPD
AB BACKGROUND: This study aimed to develop an overlap syndrome rat model with intermittent hypoxia (IH) exposure as seen in obstructive sleep apnea, on a base of preexisting emphysema caused by 16 wk of smoke exposure to determine whether IH and emphysema existing simultaneously play overlapped roles on systematic/endothelial inflammation and endothelial damage. METHODS: Sixty male Wistar rats were divided into 4 groups of 15 each, labeled according to exposure conditions as control, IH, emphysema, and overlap groups. In these animals, electroencephalogram monitoring and preliminary experiments to obtain arterial blood gas values were performed. Serum concentrations of tumor necrosis factor (TNF)-alpha and interleukin (IL)-6, TNF-alpha and IL-6 concentrations in the culture medium, Ras homology A mRNA expression levels of endothelial cells from right common carotid artery, and ratio of carotid intima-media thickness of whole thickness of vascular wall expressed in percent (C-IMT) (%) values were evaluated. Subsequently, circulating endothelial progenitor cells (EPCs) within rat peripheral blood and bone marrow were measured with flow cytometry. RESULTS: The serum and endothelial concentrations of TNF-alpha and IL-6 and the levels of endothelial Ras homology A mRNA have statistically significant results described as overlap > emphysema > IH > control. The levels of EPCs in rat peripheral blood and bone marrow have statistically significant results described as overlap > IH > emphysema > control. C-IMT (%) values from right common carotid artery are the highest in the overlap group and the lowest in the control group. There is no statistical difference when comparing the IH and the emphysema groups. CONCLUSIONS: Regardless of whether IH and emphysema exposure are mechanistically synergistic, this overlap elicits a more severe systematic/endothelial inflammation and endothelial damage; meanwhile, a robust mobilization of EPCs is demonstrated, which is not to mean a robust adherent and repairing capability. (C) 2015 Daedalus Enterprises
C1 [Yang, Qing-chan; Sun, Xin; Wang, Yong-mei; Wu, Qi] Tianjin Haihe Hosp, Tianjin 300350, Peoples R China.
[Feng, Jing; Chen, Bao-yuan] Tianjin Med Univ, Gen Hosp, Resp Dept, Tianjin 300052, Peoples R China.
[Feng, Jing] NIEHS, Neuropharmacol Sect, Lab Toxicol & Pharmacol, NIH, Res Triangle Pk, NC 27709 USA.
RP Feng, J (reprint author), Tianjin Med Univ, Gen Hosp, Resp Dept, Tianjin 300052, Peoples R China.
EM tjshhyywym@126.com; zyyhxkfj@126.com
FU National Natural Science Foundation of China [81270144, 30800507,
81170071]; Natural Science Foundation of Tianjin City [13JCYBJC22400,
13JCYBJC40000]; Tianjin Municipal Science and Technology Commission
[09ZCZDSF04500]
FX This study was supported by grants 81270144, 30800507, and 81170071 from
the National Natural Science Foundation of China; by grants
13JCYBJC22400 and 13JCYBJC40000 from the Natural Science Foundation of
Tianjin City; and by grant 09ZCZDSF04500 from the Tianjin Municipal
Science and Technology Commission. The authors have disclosed no
conflicts of interest.
NR 40
TC 2
Z9 2
U1 10
U2 12
PU DAEDALUS ENTERPRISES INC
PI IRVING
PA 9425 N MAC ARTHUR BLVD, STE 100, IRVING, TX 75063-4706 USA
SN 0020-1324
EI 1943-3654
J9 RESP CARE
JI Respir. Care
PD FEB
PY 2015
VL 60
IS 2
BP 279
EP 289
DI 10.4187/respcare.03492
PG 11
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA CD2IC
UT WOS:000350898900018
PM 25587169
ER
PT J
AU Apolo, AB
Hoffman, V
Kaag, MG
Latini, DM
Lee, CT
Rosenberg, JE
Knowles, M
Theodorescu, D
Czerniak, BA
Efstathiou, JA
Albert, ML
Sridhar, SS
Margulis, V
Matin, SF
Galsky, MD
Hansel, D
Kamat, AM
Flaig, TW
Smith, AB
Messing, E
Quale, DZ
Lotan, Y
AF Apolo, Andrea B.
Hoffman, Vanessa
Kaag, Matthew G.
Latini, David M.
Lee, Cheryl T.
Rosenberg, Jonathan E.
Knowles, Margaret
Theodorescu, Dan
Czerniak, Bogdan A.
Efstathiou, Jason A.
Albert, Matthew L.
Sridhar, Srikala S.
Margulis, Vitaly
Matin, Surena F.
Galsky, Matthew D.
Hansel, Donna
Kamat, Ashish M.
Flaig, Thomas W.
Smith, Angela B.
Messing, Edward
Quale, Diane Zipursky
Lotan, Yair
TI Summary of the 8th Annual Bladder Cancer Think Tank: Collaborating to
move research forward
SO UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS
LA English
DT Review
DE Bladder cancer; BCAN; Think Tank; Targeted therapies; Sexual
dysfunction; Gender disparities; Working groups
ID TRACT UROTHELIAL CARCINOMA; UPPER URINARY-TRACT;
TRANSITIONAL-CELL-CARCINOMA; THERAPY-ONCOLOGY-GROUP; RADICAL CYSTECTOMY;
ANDROGEN RECEPTOR; ILEAL NEOBLADDER; SCREENING TRIAL; CLINICAL-TRIAL;
LYMPH-NODES
AB Objectives: The 8th Annual Bladder Cancer Think Tank (BCAN-TT) brought together a multidisciplinary group of clinicians, researchers, and patient advocates in an effort to advance bladder cancer research.
Methods and Materials: With the theme of "Collaborating to Move Research Forward," the meeting included three panel presentations and seven small working groups.
Results: The panel presentations and interactive discussions focused on three main areas: gender disparities, sexual dysfunction, and targeting novel pathways in bladder cancer. Small working groups also met to identify projects for the upcoming year, including: (1) improving enrollment and quality of clinical trials; (2) collecting data from multiple institutions for future research; (3) evaluating patterns of care for non-muscle-invasive bladder cancer; (4) improving delivery of care for muscle-invasive disease; (5) improving quality of life for survivors; (6) addressing upper tract disease; and (7) examining the impact of health policy changes on research and treatment of bladder cancer.
Conclusions: The goal of the BCAN-TT is to advance the care of patients with bladder cancer and to promote collaborative research throughout the year. The meeting provided ample opportunities for collaboration among clinicians from multiple disciplines, patients and patient advocates, and industry representatives. (C) 2014 Elsevier Inc. All rights reserved.
C1 [Apolo, Andrea B.] NCI, Genitourinary Malignancies Branch, Bethesda, MD 20892 USA.
[Hoffman, Vanessa; Quale, Diane Zipursky] Bladder Canc Advocacy Network, Bethesda, MD USA.
[Kaag, Matthew G.] Penn State Hershey Med Ctr, Dept Urol, Hershey, PA USA.
[Latini, David M.] Baylor Coll Med, Dept Urol, Houston, TX 77030 USA.
[Lee, Cheryl T.] Univ Michigan Hlth Syst, Dept Urol, Ann Arbor, MI USA.
[Rosenberg, Jonathan E.] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA.
[Knowles, Margaret] Univ Leeds, Leeds Inst Canc & Pathol, Leeds, W Yorkshire, England.
[Theodorescu, Dan] Univ Colorado, Ctr Canc, Denver, CO 80202 USA.
[Czerniak, Bogdan A.] Univ Texas Houston, MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA.
[Efstathiou, Jason A.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Boston, MA USA.
[Albert, Matthew L.] Inst Pasteur, Dept Immunol, F-75724 Paris, France.
[Sridhar, Srikala S.] Princess Margaret Canc Ctr, Dept Med Oncol & Hematol, Toronto, ON, Canada.
[Margulis, Vitaly; Lotan, Yair] Univ Texas SW Med Ctr Dallas, Dept Urol, Dallas, TX 75390 USA.
[Matin, Surena F.; Kamat, Ashish M.] Univ Texas Houston, MD Anderson Canc Ctr, Dept Urol, Houston, TX 77030 USA.
[Galsky, Matthew D.] Mt Sinai Hosp, Dept Med Oncol, New York, NY 10029 USA.
[Hansel, Donna] Univ Calif La Jolla, Dept Pathol, San Diego, CA USA.
[Smith, Angela B.] Univ N Carolina, Dept Urol, Chapel Hill, NC USA.
[Messing, Edward] Univ Rochester, Med Ctr, Dept Urol, Rochester, NY 14642 USA.
RP Lotan, Y (reprint author), Univ Texas SW Med Ctr Dallas, Dept Urol, Dallas, TX 75390 USA.
EM yair.lotan@utsouthwestern.edu
OI Latini, David/0000-0002-6161-4861; Rosenberg,
Jonathan/0000-0003-2637-4249
NR 66
TC 2
Z9 2
U1 1
U2 8
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1078-1439
EI 1873-2496
J9 UROL ONCOL-SEMIN ORI
JI Urol. Oncol.-Semin. Orig. Investig.
PD FEB
PY 2015
VL 33
IS 2
BP 53
EP 64
DI 10.1016/j.urolonc.2014.06.013
PG 12
WC Oncology; Urology & Nephrology
SC Oncology; Urology & Nephrology
GA CD0PV
UT WOS:000350777300001
PM 25065704
ER
PT J
AU Bernstein, SL
Stoney, CM
Rothman, RE
AF Bernstein, Steven L.
Stoney, Catherine M.
Rothman, Richard E.
TI Dissemination and Implementation Research in Emergency Medicine
SO ACADEMIC EMERGENCY MEDICINE
LA English
DT Article
ID RANDOMIZED-CONTROLLED-TRIAL; BASE-LINE DESIGN; KNOWLEDGE TRANSLATION;
PRIMARY-CARE; TIME; INTERVENTIONS; IMPROVEMENT; PROTOCOL; SCIENCE; MAP
AB Published medical research takes years to change clinical practice. The reasons for this evidence-to-practice gap are many. To address this gap, in recent years the field of dissemination and implementation (D&I) science has grown dramatically. D&I studies design and test strategies to accelerate the movement of new evidence-based diagnostic and therapeutic maneuvers into real-world clinical practice. This article summarizes the proceedings of sessions at the 2011 and 2012 annual meetings of the Society for Academic Emergency Medicine that discussed D&I studies in emergency medicine. Examples of current studies are provided, along with a review of D&I methods, funding opportunities, and suggestions for future research. (C) 2015 by the Society for Academic Emergency Medicine
C1 [Bernstein, Steven L.] Yale Univ, Sch Med, Dept Emergency Med, New Haven, CT 06520 USA.
[Stoney, Catherine M.] NHLBI, NIH, Bethesda, MD 20892 USA.
[Rothman, Richard E.] Johns Hopkins, Dept Emergency Med, Baltimore, MD USA.
RP Bernstein, SL (reprint author), Yale Univ, Sch Med, Dept Emergency Med, New Haven, CT 06520 USA.
EM Steven.bernstein@yale.edu
OI Rothman, Richard/0000-0002-1017-9505
FU National Heart, Lung and Blood Institute of the National Institutes of
Health [R18HL105208]
FX Supported in part by grant R18HL105208 from the National Heart, Lung and
Blood Institute of the National Institutes of Health. The authors have
no relevant financial information or potential conflicts to disclose.
NR 36
TC 2
Z9 2
U1 2
U2 10
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1069-6563
EI 1553-2712
J9 ACAD EMERG MED
JI Acad. Emerg. Med.
PD FEB
PY 2015
VL 22
IS 2
BP 229
EP 236
DI 10.1111/acem.12588
PG 8
WC Emergency Medicine
SC Emergency Medicine
GA CC1LI
UT WOS:000350101800016
PM 25640627
ER
PT J
AU Jennings, L
Rompalo, AM
Wang, J
Hughes, J
Adimora, AA
Hodder, S
Soto-Torres, LE
Frew, PM
Haley, DF
AF Jennings, Larissa
Rompalo, Anne M.
Wang, Jing
Hughes, James
Adimora, Adaora A.
Hodder, Sally
Soto-Torres, Lydia E.
Frew, Paula M.
Haley, Danielle F.
CA HIV Prevention Trials Network HPTN
TI Prevalence and Correlates of Knowledge of Male Partner HIV Testing and
Serostatus Among African-American Women Living in High Poverty, High HIV
Prevalence Communities (HPTN 064)
SO AIDS AND BEHAVIOR
LA English
DT Article
DE Knowledge; Male sexual partner; HIV; Serostatus; African-American women
ID UNPROTECTED ANAL INTERCOURSE; SEXUAL-BEHAVIOR; UNITED-STATES; CONDOM
USE; MEN; RISK; PREVENTION; TRANSMISSION; NOTIFICATION; DISCLOSURE
AB Knowledge of sexual partners' HIV infection can reduce risky sexual behaviors. Yet, there are no published studies to-date examining prevalence and characteristics associated with knowledge among African-American women living in high poverty communities disproportionately affected by HIV. Using the HIV Prevention Trial Network's (HPTN) 064 Study data, multivariable logistic regression was used to examine individual, partner, and partnership-level determinants of women's knowledge (n = 1,768 women). Results showed that women's demographic characteristics alone did not account for the variation in serostatus awareness. Rather, lower knowledge of partner serostatus was associated with having two or more sex partners (OR = 0.49, 95 % CI 0.37-0.65), food insecurity (OR = 0.68, 95 % CI 0.49-0.94), partner age > 35 years (OR = 0.68, 95 % CI 0.49-0.94), and partner concurrency (OR = 0.63, 95 % CI 0.49-0.83). Access to financial support (OR = 1.42, 95 % CI 1.05-1.92) and coresidence (OR = 1.43, 95 % CI 1.05-1.95) were associated with higher knowledge of partner serostatus. HIV prevention efforts addressing African-American women's vulnerabilities should employ integrated behavioral, economic, and empowerment approaches.
C1 [Jennings, Larissa] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Int Hlth, Social & Behav Intervent Program, Baltimore, MD 21205 USA.
[Rompalo, Anne M.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA.
[Wang, Jing; Hughes, James] Fred Hutchinson Canc Res Ctr, Stat Ctr HIV AIDS Res & Prevent SCHARP, Seattle, WA 98104 USA.
[Hughes, James] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Adimora, Adaora A.] Univ N Carolina, Dept Med, Chapel Hill, NC USA.
[Hodder, Sally] Rutgers New Jersey Med Sch, Newark, NJ USA.
[Soto-Torres, Lydia E.] NIAID, Prevent Sci Program, DAIDS, NIH, Bethesda, MD 20892 USA.
[Frew, Paula M.] Emory Univ, Sch Med, Dept Med, Div Infect Dis, Atlanta, GA USA.
[Haley, Danielle F.] Family Hlth Int FHI 360, Durham, NC USA.
[Haley, Danielle F.] Emory Univ, Rollins Sch Publ Hlth, Dept Behav Sci & Hlth Educ, Atlanta, GA 30322 USA.
RP Jennings, L (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Dept Int Hlth, Social & Behav Intervent Program, 615 N Wolfe St,Room E5038, Baltimore, MD 21205 USA.
EM ljenning@jhsph.edu
FU University of North Carolina Clinical Trials Research Center of the
Clinical and Translational Science Award [RR 025747]; 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 Clinical and Translational Science Award
[UL1 RR 25005]; HPTN Scholars Program - National Institute of Allergy
and Infectious Diseases; National Institute of Allergy and Infectious
Diseases, National Institute on Drug Abuse; National Institute of Mental
Health [UM1 AI068619, UM 1AI068617, UM1-AI068613]; Centers for
Innovative Research to Control AIDS, Mailman School of Public Health,
Columbia University [5U1Al069466]; University of North Carolina Clinical
Trials Unit [AI069423]; University of North Carolina Center for AIDS
Research [AI050410]; Emory University HIV/AIDS Clinical Trials Unit
[5UO1AI069418]; Center for AIDS Research and Clinical and Translational
Science Award [UL1 RR025008, P30 AI050409]; Johns Hopkins Adult AIDS
Clinical Trial Unit [AI069465]; National Institute of Allergy and
Infectious Diseases
FX The authors wish to thank the study participants, community
stakeholders, and staff from each study site. In particular, we
acknowledge Lynda Emel, Jonathan Lucas, Nirupama Sista, Kathy Hinson,
Elizabeth DiNenno, Ann O'Leary, Lisa Diane White, Waheedah Shabaaz-El,
Quarraisha Abdool-Karim, Carlos del Rio, Chris Root, Valarie Hunter,
Sten Vermund, Makisha Ruffin, Genda Dockery, Charlene Wylie, Adongo
Tia-Okwee, Darrell Wheeler, Peter Winch, Magdalena Nelson, and Sam
Griffith. By the National Institute of Allergy and Infectious Diseases,
National Institute on Drug Abuse, and National Institute of Mental
Health (cooperative agreement no. UM1 AI068619, UM 1AI068617, and
UM1-AI068613); Centers for Innovative Research to Control AIDS, Mailman
School of Public Health, Columbia University (5U1Al069466); 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). The primary author's work on this manuscript was
supported through the HPTN Scholars Program funded by the National
Institute of Allergy and Infectious Diseases.
NR 31
TC 3
Z9 3
U1 2
U2 4
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 FEB
PY 2015
VL 19
IS 2
BP 291
EP 301
DI 10.1007/s10461-014-0884-y
PG 11
WC Public, Environmental & Occupational Health; Social Sciences, Biomedical
SC Public, Environmental & Occupational Health; Biomedical Social Sciences
GA CC4UL
UT WOS:000350349300009
PM 25160901
ER
PT J
AU Mannisto, T
Mendola, P
Liu, DP
Leishear, K
Ying, Q
Sundaram, R
AF Maennistoe, Tuija
Mendola, Pauline
Liu, Danping
Leishear, Kira
Ying, Qi
Sundaram, Rajeshwari
TI Temporal variation in the acute effects of air pollution on blood
pressure measured at admission to labor/delivery
SO AIR QUALITY ATMOSPHERE AND HEALTH
LA English
DT Article
DE Epidemiology; Blood pressure; Pregnancy; Air pollution; Temporal
variation
ID AMERICAN-HEART-ASSOCIATION; CARDIOVASCULAR-DISEASE; PARTICULATE MATTER;
SYSTEMIC INFLAMMATION; NORMAL-PREGNANCY; PULSE PRESSURE; HYPERTENSION;
EXPOSURE; POPULATION; CONSTITUENTS
AB Same day or recent air pollution exposure increases blood pressure in pregnant women. Temporal blood pressure variation associated with hourly air pollution is unstudied. We randomly selected 500 women (249 normotensive, 191 with hypertensive disorders, and 60 with chronic hypertension) with singleton pregnancies and blood pressure measured at labor/delivery admission from a large cohort, the Consortium on Safe Labor. Community multiscale air quality models estimated hourly air pollutant exposures for the admission hour (lag 0) and for the 24 h preceding labor/delivery admission (lags 1-24). Linear regression estimated the effect of 10 % increase in pollutants on blood pressure at each time point, adjusting for maternal characteristics, labor type, and time of day. Women with chronic hypertension had higher systolic blood pressure with exposure to particulate matter < 10 mu m (by 1.0-1.3 mmHg at 0-4 h), sulfur dioxide (by 0.7-0.9 mmHg at 0-3, 16-20, and 22-23 h) and with some air toxics. Diastolic blood pressure was higher in normotensive women with ozone exposure (by 0.1-0.4 mmHg at 0-1 and 23-24 h). Similar effects for systolic blood pressure were seen among women with hypertensive disorders (by 0.6 mmHg at 19-20 h), but most pollutants were associated with lower blood pressure in these women. Substantial variation in the impact of hourly air pollutant measures on blood pressure was observed during the day prior to labor/delivery admission, both by mothers' hypertensive status and by the lag time prior to BP measurement. Effects were largest near admission (lags 0-4) and among women with chronic hypertension.
C1 [Maennistoe, Tuija; Mendola, Pauline] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, Epidemiol Branch, NIH, Rockville, MD 20852 USA.
[Liu, Danping; Sundaram, Rajeshwari] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, Biostat & Bioinformat Branch, NIH, Rockville, MD 20852 USA.
[Leishear, Kira] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, NIH, Rockville, MD 20852 USA.
[Ying, Qi] Texas A&M Univ, Zachry Dept Civil Engn, TAMU 3136, College Stn, TX 77843 USA.
RP Mendola, P (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, Epidemiol Branch, NIH, 6100 Executive Blvd,7B05, Rockville, MD 20852 USA.
EM pauline.mendola@nih.gov
OI Mannisto, Tuija/0000-0002-6382-9153; Mendola,
Pauline/0000-0001-5330-2844; Sundaram, Rajeshwari/0000-0002-6918-5002
FU Intramural Research Program of the Eunice Kennedy Shriver National
Institute of Child Health and Human Development, National Institutes of
Health; [HHSN267200603425C]; [HHSN275200800002I]; [HHSN27500008]
FX This work was supported by the Intramural Research Program of the Eunice
Kennedy Shriver National Institute of Child Health and Human
Development, National Institutes of Health. The data included in this
paper were obtained from the Consortium on Safe Labor and the Air
Quality and Reproductive Health study, which were supported by the
Intramural Research Program of the Eunice Kennedy Shriver National
Institute of Child Health and Human Development, National Institutes of
Health. The Consortium on Safe Labor was supported through Contract No.
HHSN267200603425C, and the Air Quality and Reproductive Health study was
supported through Contract No. HHSN275200800002I, Task Order No.
HHSN27500008. Institutions involved in the Consortium include, in
alphabetical order: Baystate Medical Center, Springfield, MA;
Cedars-Sinai Medical Center Burnes Allen Research Center, Los Angeles,
CA; Christiana Care Health System, Newark, DE; Georgetown University
Hospital, MedStar Health, Washington, DC; Indiana University Clarian
Health, Indianapolis, IN; Intermountain Healthcare and the University of
Utah, Salt Lake City, Utah; Maimonides Medical Center, Brooklyn, NY;
MetroHealth Medical Center, Cleveland, OH.; Summa Health System, Akron
City Hospital, Akron, OH; The EMMES Corporation, Rockville MD (data
coordinating center); University of Illinois at Chicago, Chicago, IL;
University of Miami, Miami, FL; and University of Texas Health Science
Center at Houston, Houston, Texas. The authors also want to acknowledge
the Texas A&M Supercomputing Facility (http://sc.tamu.edu) and the Texas
Advanced Computing Center (http://www.tacc.utexas.edu/) for providing
computing resources essential for completing the air quality simulations
used for exposure estimations described in this study.
NR 37
TC 0
Z9 0
U1 0
U2 6
PU SPRINGER INTERNATIONAL PUBLISHING AG
PI CHAM
PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND
SN 1873-9318
EI 1873-9326
J9 AIR QUAL ATMOS HLTH
JI Air Qual. Atmos. Health
PD FEB
PY 2015
VL 8
IS 1
BP 13
EP 28
DI 10.1007/s11869-014-0268-5
PG 16
WC Environmental Sciences
SC Environmental Sciences & Ecology
GA CC3FX
UT WOS:000350232900002
ER
PT J
AU McDonald, PG
O'Connell, M
Suls, J
AF McDonald, Paige Green
O'Connell, Mary
Suls, Jerry
TI Cancer Control Falls Squarely Within the Province of the Psychological
Sciences
SO AMERICAN PSYCHOLOGIST
LA English
DT Article
DE psychology; cancer prevention; cancer control; behavioral medicine
ID METASTATIC BREAST-CANCER; UNITED-STATES; DECISION-MAKING; PSYCHOSOCIAL
FACTORS; BEHAVIORAL-RESEARCH; PANCREATIC-CANCER; RANDOMIZED-TRIALS;
PRONE PERSONALITY; PHYSICAL-ACTIVITY; COGNITIVE CHANGES
AB Against the background of cancer as a contemporary public health challenge, this article presents a selective overview of psychological science contributions to cancer control research, practice, and policy. Initial contributions were circumscribed to awareness campaigns and the assessment of emotional responses to diagnosis and treatment. As evidence linking certain behaviors to cancer risk and outcomes accumulated, psychology emerged as a "hub science" in the Nation's cancer control program. Despite substantial accomplishments, new societal trends further challenge our ability to reduce risk, incidence, and deaths from cancer and enhance quality of life for cancer survivors. Evidence generated from psychological research conducted within each cell of Pasteur's quadrant continues to be relevant and necessary for effective 21st-century approaches to cancer prevention and control at the individual, clinical, and population levels.
C1 [McDonald, Paige Green; O'Connell, Mary; Suls, Jerry] NCI, Behav Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
RP McDonald, PG (reprint author), 9609 Med Ctr Dr,MSC 9761, Rockville, MD 20850 USA.
EM mcdonalp@mail.nih.gov
OI Green, Paige/0000-0001-7886-8924
NR 187
TC 2
Z9 2
U1 0
U2 9
PU AMER PSYCHOLOGICAL ASSOC
PI WASHINGTON
PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA
SN 0003-066X
EI 1935-990X
J9 AM PSYCHOL
JI Am. Psychol.
PD FEB-MAR
PY 2015
VL 70
IS 2
SI SI
BP 61
EP 74
DI 10.1037/a0038873
PG 14
WC Psychology, Multidisciplinary
SC Psychology
GA CC7OE
UT WOS:000350556800001
ER
PT J
AU McBride, CM
Birmingham, WC
Kinney, AY
AF McBride, Colleen M.
Birmingham, Wendy C.
Kinney, Anita Y.
TI Health Psychology and Translational Genomic Research Bringing Innovation
to Cancer-Related Behavioral Interventions
SO AMERICAN PSYCHOLOGIST
LA English
DT Article
DE genomics; translational research; health psychology; cancer; behavior
ID AT-RISK RELATIVES; NONPOLYPOSIS COLORECTAL-CANCER; RANDOMIZED
CONTROLLED-TRIAL; SOCIAL-SCIENCES RESEARCH; BREAST-CANCER; HEREDITARY
BREAST; OVARIAN-CANCER; GENETIC SUSCEPTIBILITY; FAMILY-HISTORY; LYNCH
SYNDROME
AB The past decade has witnessed rapid advances in human genome sequencing technology and in the understanding of the role of genetic and epigenetic alterations in cancer development. These advances have raised hopes that such knowledge could lead to improvements in behavioral risk reduction interventions, tailored screening recommendations, and treatment matching that together could accelerate the war on cancer. Despite this optimism, translation of genomic discovery for clinical and public health applications has moved relatively slowly. To date, health psychologists and the behavioral sciences generally have played a very limited role in translation research. In this report we discuss what we mean by genomic translational research and consider the social forces that have slowed translational research, including normative assumptions that translation research must occur downstream of basic science, thus relegating health psychology and other behavioral sciences to a distal role. We then outline two broad priority areas in cancer prevention, detection, and treatment where evidence will be needed to guide evaluation and implementation of personalized genomics: (a) effective communication, to broaden dissemination of genomic discovery, including patient-provider communication and familial communication, and (b) the need to improve the motivational impact of behavior change interventions, including those aimed at altering lifestyle choices and those focusing on decision making regarding targeted cancer treatments and chemopreventive adherence. We further discuss the role that health psychologists can play in interdisciplinary teams to shape translational research priorities and to evaluate the utility of emerging genomic discoveries for cancer prevention and control.
C1 [McBride, Colleen M.] NHGRI, Bethesda, MD 20892 USA.
[Birmingham, Wendy C.] Brigham Young Univ, Dept Psychol, Provo, UT 84602 USA.
[Kinney, Anita Y.] Univ New Mexico, Ctr Canc, Dept Internal Med, Div Epidemiol Biostat & Prevent Med, Albuquerque, NM 87131 USA.
RP McBride, CM (reprint author), NHGRI, Bldg 31,MSC 2073,31 Ctr Dr,Room B1B54, Bethesda, MD 20892 USA.
EM cmcbride@mail.nih.gov
NR 122
TC 4
Z9 4
U1 1
U2 22
PU AMER PSYCHOLOGICAL ASSOC
PI WASHINGTON
PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA
SN 0003-066X
EI 1935-990X
J9 AM PSYCHOL
JI Am. Psychol.
PD FEB-MAR
PY 2015
VL 70
IS 2
SI SI
BP 91
EP 104
DI 10.1037/a0036568
PG 14
WC Psychology, Multidisciplinary
SC Psychology
GA CC7OE
UT WOS:000350556800003
PM 25730717
ER
PT J
AU Reyna, VF
Nelson, WL
Han, PK
Pignone, MP
AF Reyna, Valerie F.
Nelson, Wendy L.
Han, Paul K.
Pignone, Michael P.
TI Decision Making and Cancer
SO AMERICAN PSYCHOLOGIST
LA English
DT Article
DE heuristics and biases; decision aids; medical decision making; informed
decision making; risk communication
ID FUZZY-TRACE THEORY; SERVICES TASK-FORCE; BREAST-CANCER; PROSTATE-CANCER;
RISK PERCEPTION; ACTIVE SURVEILLANCE; RECOMMENDATION STATEMENT;
FERTILITY PRESERVATION; PERCEIVED AMBIGUITY; RATIONAL CHOICE
AB We review decision making along the cancer continuum in the contemporary context of informed and shared decision making in which patients are encouraged to take a more active role in their health care. We discuss challenges to achieving informed and shared decision making, including cognitive limitations and emotional factors, but argue that understanding the mechanisms of decision making offers hope for improving decision support. Theoretical approaches to decision making that explain cognition, emotion, and their interaction are described, including classical psychophysical approaches, dual-process approaches that focus on conflicts between emotion versus cognition (or reason), and modern integrative approaches such as fuzzy-trace theory. In contrast to the earlier emphasis on rote use of numerical detail, modern approaches emphasize understanding the bottom-line gist of options (which encompasses emotion and other influences on meaning) and retrieving relevant social and moral values to apply to those gist representations. Finally, research on interventions to support better decision making in clinical settings is reviewed, drawing out implications for future research on decision making and cancer.
C1 [Reyna, Valerie F.] Cornell Univ, Human Neurosci Inst, Ithaca, NY 14853 USA.
[Reyna, Valerie F.] Cornell Univ, Ctr Behav Econ & Decis Res, Ithaca, NY 14853 USA.
[Nelson, Wendy L.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Han, Paul K.] Maine Med Ctr, Ctr Outcomes Res & Evaluat, Scarborough, ME USA.
[Pignone, Michael P.] Univ N Carolina, Div Gen Internal Med, Chapel Hill, NC USA.
RP Reyna, VF (reprint author), Cornell Univ, Human Neurosci Inst, G331,Martha Van Rensselaer Hall, Ithaca, NY 14853 USA.
EM vr53@cornell.edu
OI Han, Paul/0000-0003-0165-1940
FU National Cancer Institute of the National Institutes of Health
[R21CA149796]; National Institute of Nursing Research [RO1NR014368-01];
National Cancer Institute [K05 CA129166]
FX Preparation of this manuscript was supported in part by awards from the
National Cancer Institute of the National Institutes of Health
(R21CA149796) and the National Institute of Nursing Research
(RO1NR014368-01) to Valerie F. Reyna and by an Established Investigator
Award from the National Cancer Institute (K05 CA129166) to Michael P.
Pignone.
NR 128
TC 22
Z9 22
U1 11
U2 37
PU AMER PSYCHOLOGICAL ASSOC
PI WASHINGTON
PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA
SN 0003-066X
EI 1935-990X
J9 AM PSYCHOL
JI Am. Psychol.
PD FEB-MAR
PY 2015
VL 70
IS 2
SI SI
BP 105
EP 118
DI 10.1037/a0036834
PG 14
WC Psychology, Multidisciplinary
SC Psychology
GA CC7OE
UT WOS:000350556800004
PM 25730718
ER
PT J
AU Stanton, AL
Rowland, JH
Ganz, PA
AF Stanton, Annette L.
Rowland, Julia H.
Ganz, Patricia A.
TI Life After Diagnosis and Treatment of Cancer in Adulthood Contributions
From Psychosocial Oncology Research
SO AMERICAN PSYCHOLOGIST
LA English
DT Article
DE cancer; survivorship; psychosocial; quality of life; intervention
ID QUALITY-OF-LIFE; POSTTRAUMATIC-STRESS-DISORDER; STAGE BREAST-CANCER;
RANDOMIZED CONTROLLED-TRIAL; LOCALIZED PROSTATE-CANCER; PROBLEM-SOLVING
THERAPY; NON-HODGKIN-LYMPHOMA; LONG-TERM SURVIVORS; COLORECTAL-CANCER;
DEPRESSIVE SYMPTOMS
AB The number of individuals living with a history of cancer is estimated at 13.7 million in the United States and is expected to rise with the aging of the population. With expanding attention to the psychosocial and physical consequences of surviving illness, psychological science and evidence-based practice are making important contributions to addressing the pressing needs of cancer survivors. Research is demonstrating that adults diagnosed with cancer evidence generally positive psychosocial adjustment over time; however, a subset is at risk for compromised psychological and physical health stemming from long-term or late effects of cancer and its treatment. In this article, we characterize survivorship after medical treatment completion during the periods of reentry, early survivorship, and long-term survivorship. We describe the major psychosocial and physical sequelae facing adults during those periods, highlight promising posttreatment psychosocial and behavioral interventions, and offer recommendations for future research and evidence-based practice.
C1 [Stanton, Annette L.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90095 USA.
[Rowland, Julia H.] NCI, Bethesda, MD 20892 USA.
[Ganz, Patricia A.] Univ Calif Los Angeles, Fielding Sch Publ Hlth, Los Angeles, CA 90095 USA.
[Ganz, Patricia A.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
RP Stanton, AL (reprint author), Univ Calif Los Angeles, Dept Psychol, 1285 Franz Hall,Box 951563, Los Angeles, CA 90095 USA.
EM astanton@ucla.edu
NR 187
TC 12
Z9 13
U1 9
U2 26
PU AMER PSYCHOLOGICAL ASSOC
PI WASHINGTON
PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA
SN 0003-066X
EI 1935-990X
J9 AM PSYCHOL
JI Am. Psychol.
PD FEB-MAR
PY 2015
VL 70
IS 2
SI SI
BP 159
EP 174
DI 10.1037/a0037875
PG 16
WC Psychology, Multidisciplinary
SC Psychology
GA CC7OE
UT WOS:000350556800008
PM 25730722
ER
PT J
AU Hesse, BW
Beckjord, E
Rutten, LJF
Fagerlin, A
Cameron, LD
AF Hesse, Bradford W.
Beckjord, Ellen
Rutten, Lila J. Finney
Fagerlin, Angela
Cameron, Linda D.
TI Cancer Communication and Informatics Research Across the Cancer
Continuum
SO AMERICAN PSYCHOLOGIST
LA English
DT Article
DE health communication; informatics; psycho-oncology; cancer
ID DECISION-MAKING; SMOKING-CESSATION; MOBILE TECHNOLOGY; SOCIAL IMAGE;
HEALTH-CARE; INTERVENTIONS; PATIENT; BREAST; IMPACT; PERSPECTIVE
AB Over the past decade, dramatic changes brought about by a rapid diffusion of Internet technologies, cellular telephones, mobile devices, personal digital assistants, electronic health records, and data visualization have helped to create a revolution in health communication. To understand the implications of this communication revolution for cancer care, the National Cancer Institute launched an ambitious set of research priorities under its "extraordinary opportunities" program. We present an overview of some of the relevant behavioral research being conducted within the perspective of this extraordinary opportunity in cancer communication research. We begin by tracing the implications of this research for behavioral scientists across the continuum of cancer care from primary prevention (e.g., tobacco control, diet, exercise, sun protection, and immunization against human papilloma virus), to secondary prevention (e.g., screening for polyps, lesions, and early stage neoplasms), to diagnosis and treatment, post-treatment survivorship, and end of life. Along each point of the continuum, we describe a natural evolution of knowledge from studies on the traditional role of media to research on the changing role of new media and informatics, and we carefully highlight the role that psychological research has played in improving communication-and health-related outcomes along the way. We conclude with an appeal to psychologists of many different backgrounds to join with biomedical researchers, engineers, clinical practitioners, and others to accelerate progress against cancer.
C1 [Hesse, Bradford W.] NCI, Hlth Commun & Informat Res Branch, Bethesda, MD 20892 USA.
[Beckjord, Ellen] Univ Pittsburgh, Biobehav Med Oncol Program, Pittsburgh, PA 15260 USA.
[Rutten, Lila J. Finney] Mayo Clin, Dept Hlth Sci Res, Populat Hlth Sci Program, Rochester, MN USA.
[Fagerlin, Angela] Univ Michigan, Ctr Bioeth & Social Sci Med, Ann Arbor, MI 48109 USA.
[Fagerlin, Angela] VA Ctr Clin Management Res, Ann Arbor, MI USA.
[Cameron, Linda D.] Univ Calif, Hlth Commun & Intervent Lab, Merced, CA USA.
[Cameron, Linda D.] Univ Calif, Dept Psychol, Merced, CA USA.
RP Hesse, BW (reprint author), NCI, Hlth Commun & Informat Res Branch, 9609 Med Ctr Dr, Bethesda, MD 20892 USA.
EM bradford.hesse@nih.gov
OI Hesse, Bradford/0000-0003-1142-1161
NR 110
TC 4
Z9 4
U1 4
U2 16
PU AMER PSYCHOLOGICAL ASSOC
PI WASHINGTON
PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA
SN 0003-066X
EI 1935-990X
J9 AM PSYCHOL
JI Am. Psychol.
PD FEB-MAR
PY 2015
VL 70
IS 2
SI SI
BP 198
EP 210
DI 10.1037/a0036852
PG 13
WC Psychology, Multidisciplinary
SC Psychology
GA CC7OE
UT WOS:000350556800011
PM 25730725
ER
PT J
AU Rabin, B
Glasgow, RE
AF Rabin, Borsika
Glasgow, Russell E.
TI An Implementation Science Perspective on Psychological Science and
Cancer What Is Known and Opportunities for Research, Policy, and
Practice
SO AMERICAN PSYCHOLOGIST
LA English
DT Article
DE implementation; cancer; review; recommendations; psychological science
ID PUBLIC-HEALTH; QUALITY-IMPROVEMENT; PRECISION MEDICINE;
DIFFUSION-THEORY; TRANSLATION; CARE; DISSEMINATION; INTERVENTIONS;
KNOWLEDGE; FUTURE
AB We discuss the role of implementation science in cancer and summarize the need for this perspective. Following a summary of key implementation science principles and lessons learned, we review the literature on implementation of cancer prevention and control activities across the continuum from prevention to palliative care. We identified 10 unique relevant reviews, four of which were specific to cancer. Multicomponent implementation strategies were found to be superior to single-component interventions, but it was not possible to draw conclusions about specific strategies or the range of conditions across which strategies were effective. Particular gaps identified include the need for more studies of health policies and reports of cost, cost-effectiveness, and resources required. Following this review, we summarize the types of evidence needed to make research findings more actionable and discuss emerging implementation science opportunities for psychological research on cancer prevention and control. These include innovative study designs (i.e., rapid learning designs, simulation modeling, comparative effectiveness, pragmatic studies, mixed-methods research) and measurement science (i.e., development of context-relevant measures; practical, longitudinal measures to gauge improvement; cost-effectiveness data; and harmonized patient report data). We conclude by identifying a few grand challenges for psychologists that if successfully addressed would accelerate integration of evidence into cancer practice and policy more consistently and rapidly.
C1 [Rabin, Borsika] Kaiser Permanente Colorado, CRN Canc Commun Res Ctr, Inst Hlth Res, Denver, CO USA.
[Glasgow, Russell E.] NCI, Div Canc Control & Populat Sci, Rockville, MD USA.
[Glasgow, Russell E.] Univ Colorado, Sch Med, Dept Family Med, Aurora, CO 80045 USA.
RP Glasgow, RE (reprint author), Univ Colorado, Sch Med, Colorado Hlth Outcomes Program, 13199 East Montview Blvd,Suite 300,Mail Stop F443, Aurora, CO 80045 USA.
EM russell.glasgow@ucdenver.edu
FU National Cancer Institute Centers of Excellence in Cancer Communication
Research [P20CA137219]
FX Funding for the preparation of this manuscript was partially provided
through the National Cancer Institute Centers of Excellence in Cancer
Communication Research (Award P20CA137219). The opinions expressed in
this article are those of the authors and do not necessarily represent
those of the National Cancer Institute.
NR 71
TC 2
Z9 2
U1 0
U2 5
PU AMER PSYCHOLOGICAL ASSOC
PI WASHINGTON
PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA
SN 0003-066X
EI 1935-990X
J9 AM PSYCHOL
JI Am. Psychol.
PD FEB-MAR
PY 2015
VL 70
IS 2
SI SI
BP 211
EP 220
DI 10.1037/a0036107
PG 10
WC Psychology, Multidisciplinary
SC Psychology
GA CC7OE
UT WOS:000350556800012
PM 25730726
ER
PT J
AU Croyle, RT
AF Croyle, Robert T.
TI Risks and Opportunities for Psychology's Contribution to the War on
Cancer
SO AMERICAN PSYCHOLOGIST
LA English
DT Article
DE cancer
ID RECOMMENDATIONS
AB This special issue of American Psychologist reviews a broad, diverse, and growing research literature that has established the discipline as an essential source of evidence concerning cancer prevention and control. Nevertheless, the history of psychological science that is intended to inform cancer control suggests a number of risks going forward that could attenuate the impact of this work. Fortunately, the field also faces new opportunities to contribute more substantially, especially if psychologists engage the broader biomedical and public health communities through rigorous, relevant, multilevel research that is informed by current knowledge of the disease and its treatment, the skills required to participate in large-scale transdisciplinary team science, and an appreciation of the economic, organizational, and policy context of cancer control at the local and national levels.
C1 [Croyle, Robert T.] NCI, Bethesda, MD 20892 USA.
RP Croyle, RT (reprint author), NCI, Div Canc Control & Populat Sci, 9609 Med Ctr Dr, Bethesda, MD 20892 USA.
EM croyler@mail.nih.gov
NR 17
TC 2
Z9 2
U1 1
U2 2
PU AMER PSYCHOLOGICAL ASSOC
PI WASHINGTON
PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA
SN 0003-066X
EI 1935-990X
J9 AM PSYCHOL
JI Am. Psychol.
PD FEB-MAR
PY 2015
VL 70
IS 2
SI SI
BP 221
EP 224
DI 10.1037/a0038869
PG 4
WC Psychology, Multidisciplinary
SC Psychology
GA CC7OE
UT WOS:000350556800013
PM 25730727
ER
PT J
AU Ravenscroft, G
Laing, NG
Bonnemann, CG
AF Ravenscroft, Gianina
Laing, Nigel G.
Boennemann, Carsten G.
TI Pathophysiological concepts in the congenital myopathies: blurring the
boundaries, sharpening the focus
SO BRAIN
LA English
DT Review
DE congenital myopathy; pathophysiology; mitochondria; membrane
remodelling; force generation; atrophy; autophagy; triad;
excitation-contraction coupling
ID MYOSIN HEAVY-CHAIN; ENZYME REPLACEMENT THERAPY; DUCHENNE
MUSCULAR-DYSTROPHY; FIBER-TYPE DISPROPORTION; SKELETAL-MUSCLE ACTIN;
RECESSIVE NEMALINE MYOPATHY; CAUSE DISTAL ARTHROGRYPOSIS; LINKED
MYOTUBULAR MYOPATHY; BETA-TROPOMYOSIN MUTATION; DOMINANT ACTA1 DISEASE
AB The congenital myopathies are a diverse group of genetic skeletal muscle diseases, which typically present at birth or in early infancy. There are multiple modes of inheritance and degrees of severity (ranging from foetal akinesia, through lethality in the newborn period to milder early and later onset cases). Classically, the congenital myopathies are defined by skeletal muscle dysfunction and a non-dystrophic muscle biopsy with the presence of one or more characteristic histological features. However, mutations in multiple different genes can cause the same pathology and mutations in the same gene can cause multiple different pathologies. This is becoming ever more apparent now that, with the increasing use of next generation sequencing, a genetic diagnosis is achieved for a greater number of patients. Thus, considerable genetic and pathological overlap is emerging, blurring the classically established boundaries. At the same time, some of the pathophysiological concepts underlying the congenital myopathies are moving into sharper focus. Here we explore whether our emerging understanding of disease pathogenesis and underlying pathophysiological mechanisms, rather than a strictly gene-centric approach, will provide grounds for a different and perhaps complementary grouping of the congenital myopathies, that at the same time could help instil the development of shared potential therapeutic approaches. Stemming from recent advances in the congenital myopathy field, five key pathophysiology themes have emerged: defects in (i) sarcolemmal and intracellular membrane remodelling and excitation-contraction coupling; (ii) mitochondrial distribution and function; (iii) myofibrillar force generation; (iv) atrophy; and (v) autophagy. Based on numerous emerging lines of evidence from recent studies in cell lines and patient tissues, mouse models and zebrafish highlighting these unifying pathophysiological themes, here we review the congenital myopathies in relation to these emerging pathophysiological concepts, highlighting both areas of overlap between established entities, as well as areas of distinction within single gene disorders.
C1 [Ravenscroft, Gianina; Laing, Nigel G.] Univ Western Australia, Harry Perkins Inst Med Res, Med Res Ctr, Nedlands, WA 6009, Australia.
[Boennemann, Carsten G.] NINDS, NIH, Porter Neurosci Res Ctr, Bethesda, MD 20892 USA.
RP Bonnemann, CG (reprint author), NINDS, Neuromuscular & Neurogenet Disorders Childhood Se, Neurogenet Branch, NIH, 35 Convent Dr,Bldg 35,Room 2A-116, Bethesda, MD 20892 USA.
EM carsten.bonnemann@nih.gov
FU National Health and Medical Research Council of Australia (NHRMC) Early
Career Researcher Fellowship [APP1035955]; NHMRC Research Fellowship
[APP1002147]; NINDS/NIH
FX G.R. is supported by a National Health and Medical Research Council of
Australia (NHRMC) Early Career Researcher Fellowship (APP1035955) and
N.G.L. by a NHMRC Research Fellowship (APP1002147). C.G.B. is supported
by intramural funds of NINDS/NIH.
NR 212
TC 13
Z9 14
U1 0
U2 5
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 FEB 1
PY 2015
VL 138
BP 246
EP 268
DI 10.1093/brain/awu368
PN 2
PG 23
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA CC2YA
UT WOS:000350209900016
PM 25552303
ER
PT J
AU Zeuner, KE
Knutzen, A
Granert, O
Gotz, J
Wolff, S
Jansen, O
Dressler, D
Hefter, H
Hallett, M
Deuschl, G
van Eimeren, T
Witt, K
AF Zeuner, Kirsten E.
Knutzen, Arne
Granert, Oliver
Goetz, Julia
Wolff, Stephan
Jansen, Olav
Dressler, Dirk
Hefter, Harald
Hallett, Mark
Deuschl, Guenther
van Eimeren, Thilo
Witt, Karsten
TI Increased volume and impaired function: the role of the basal ganglia in
writer's cramp
SO BRAIN AND BEHAVIOR
LA English
DT Article
DE Focal hand dystonia; functional magnetic resonance imaging; motor
learning; voxel-based morphometry; writer's cramp
ID FOCAL HAND DYSTONIA; VOXEL-BASED MORPHOMETRY; PRIMARY MOTOR CORTEX;
GRAY-MATTER CHANGES; EVENT-RELATED FMRI; FINGER MOVEMENTS; CEREBELLAR
ACTIVATION; CERVICAL DYSTONIA; TASK COMPLEXITY; BRAIN
AB IntroductionThe pathophysiology of writer's cramp, a task-specific dystonia, remains unclear. The objective of this study was to investigate the basal ganglia circuit and the cerebellum during a complex motor sequence learning task carried out with the nonaffected hand in writer's cramp patients. MethodsWe applied structural and functional imaging in 22 writer's cramp patients and 28 matched controls using 3T MRI. With the asymptomatic left hand all participants learned a complex, sequential, five-element sequence-tapping task as accurately and quickly as possible. Functional imaging was measured during a repeated (15 times), fixed block design with tapping (30sec) and rest (30sec). Additionally, gray matter volume of the basal ganglia was analyzed using voxel-based morphometry (VBM). ResultsWhile behavior was comparable between groups, after small volume correction the anterior part of the right putamen and the left globus pallidus exhibited reduced blood oxygen level-dependent (BOLD) activity in patients during the sequential finger-tapping task. VBM analysis showed larger gray matter volume bilateral in the posterior part of the putamen and globus pallidus. There were no group differences in the cerebellum. ConclusionThe results indicate an impairment of anterior basal ganglia loops involved in producing complex sequential movements of the unaffected hand. These findings are in line with previous reports of reduced neuronal activity in the globus pallidus internus. Higher gray matter volume of the putamen and globus pallidus may stem from elevated activity of the direct pathway, which could reflect a compensatory phenomenon or a primary predisposition, that is, endophenotypic trait.
C1 [Zeuner, Kirsten E.; Knutzen, Arne; Granert, Oliver; Goetz, Julia; Deuschl, Guenther; van Eimeren, Thilo; Witt, Karsten] Univ Kiel, Dept Neurol, D-24105 Kiel, Germany.
[Wolff, Stephan; Jansen, Olav] Univ Kiel, Dept Neuroradiol, D-24105 Kiel, Germany.
[Dressler, Dirk] Hannover Med Sch, Dept Neurol, Movement Disorders Sect, Hannover, Germany.
[Hefter, Harald] Univ Dusseldorf, Dept Neurol, Dusseldorf, Germany.
[Hallett, Mark] NINDS, Human Motor Control Sect, Med Neurol Branch, NIH, Bethesda, MD 20892 USA.
RP Zeuner, KE (reprint author), Univ Kiel, Dept Neurol, Arnold Heller Str 3,Haus 41, D-24105 Kiel, Germany.
EM k.zeuner@neurologie.uni-kiel.de
RI Deuschl, Gunther/A-7986-2010
FU Christian Albrechts-University of Kiel
FX We are indebted to the patients and normal volunteers for participating
in this study. This study has been supported by an intramural grant from
the Christian Albrechts-University of Kiel.
NR 77
TC 3
Z9 3
U1 1
U2 6
PU JOHN WILEY & SONS INC
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN, NJ 07030 USA
SN 2162-3279
J9 BRAIN BEHAV
JI Brain Behav.
PD FEB
PY 2015
VL 5
IS 2
AR e00301
DI 10.1002/brb3.301
PG 14
WC Behavioral Sciences; Neurosciences
SC Behavioral Sciences; Neurosciences & Neurology
GA CC3OZ
UT WOS:000350260100003
PM 25642386
ER
PT J
AU Parameswaran, B
Chiang, HC
Lu, YZ
Coates, J
Deng, CX
Baer, R
Lin, HK
Li, R
Paull, TT
Hu, YF
AF Parameswaran, Balaji
Chiang, Huai-Chin
Lu, Yunzhe
Coates, Julia
Deng, Chu-Xia
Baer, Richard
Lin, Hui-Kuan
Li, Rong
Paull, Tanya T.
Hu, Yanfen
TI Damage-induced BRCA1 phosphorylation by Chk2 contributes to the timing
of end resection
SO CELL CYCLE
LA English
DT Article
DE BRCA1; cell cycle; DNA double-strand break repair; end-resection; SCF
ID STRAND-BREAK REPAIR; DNA-DAMAGE; CELL-CYCLE; HOMOLOGOUS RECOMBINATION;
DEPENDENT PHOSPHORYLATION; GENOMIC STABILITY; COMPLEX-FORMATION;
TUMOR-SUPPRESSOR; CTIP; CANCER
AB The BRCA1 tumor suppressor plays an important role in homologous recombination (HR)-mediated DNA double-strand-break (DSB) repair. BRCA1 is phosphorylated by Chk2 kinase upon gamma-irradiation, but the role of Chk2 phosphorylation is not understood. Here, we report that abrogation of Chk2 phosphorylation on BRCA1 delays end resection and the dispersion of BRCA1 from DSBs but does not affect the assembly of Mre11/Rad50/NBS1 (MRN) and CtIP at DSBs. Moreover, we show that BRCA1 is ubiquitinated by SCFSkp2 and that abrogation of Chk2 phosphorylation impairs its ubiquitination. Our study suggests that BRCA1 is more than a scaffold protein to assemble HR repair proteins at DSBs, but that Chk2 phosphorylation of BRCA1 also serves as a built-in clock for HR repair of DSBs. BRCA1 is known to inhibit Mre11 nuclease activity. SCFSkp2 activity appears at late G1 and peaks at S/G2, and is known to ubiquitinate phosphodegron motifs. The removal of BRCA1 from DSBs by SCFSkp2-mediated degradation terminates BRCA1-mediated inhibition of Mre11 nuclease activity, allowing for end resection and restricting the initiation of HR to the S/G2 phases of the cell cycle.
C1 [Parameswaran, Balaji; Chiang, Huai-Chin; Lu, Yunzhe; Li, Rong; Hu, Yanfen] Univ Texas Hlth Sci Ctr San Antonio, Dept Mol Med, San Antonio, TX 78229 USA.
[Coates, Julia] Wellcome Trust Res Labs, Cambridge, England.
[Coates, Julia] Canc Res UK Gurdon Inst, Cambridge, England.
[Coates, Julia] Univ Cambridge, Dept Zool, Cambridge, England.
[Deng, Chu-Xia] NIDDK, Genet Dev & Dis Branch, Bethesda, MD 20892 USA.
[Baer, Richard] Columbia Univ, Dept Pathol, Inst Canc Genet, New York, NY USA.
[Lin, Hui-Kuan] Univ Texas MD Anderson Canc Ctr, Dept Mol & Cellular Oncol, Houston, TX 77030 USA.
[Paull, Tanya T.] Univ Texas Austin, Dept Mol Genet & Microbiol, Austin, TX 78712 USA.
RP Hu, YF (reprint author), Univ Texas Hlth Sci Ctr San Antonio, Dept Mol Med, San Antonio, TX 78229 USA.
EM huy3@uthscsa.edu
RI deng, chuxia/N-6713-2016;
OI Parameswaran, Balaji/0000-0002-1665-4872
FU National Institutes of Health [R01CA118578]; cancer center support grant
[P30CA054174]
FX The study was supported by National Institutes of Health Grant (to YH)
R01CA118578 and the cancer center support grant P30CA054174.
NR 51
TC 4
Z9 6
U1 0
U2 3
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 1538-4101
EI 1551-4005
J9 CELL CYCLE
JI Cell Cycle
PD FEB 1
PY 2015
VL 14
IS 3
BP 437
EP 448
DI 10.4161/15384101.2014.972901
PG 12
WC Cell Biology
SC Cell Biology
GA CC1WW
UT WOS:000350137100022
PM 25659039
ER
PT J
AU Morozko, EL
Nishio, A
Ingham, NJ
Chandra, R
Fitzgerald, T
Martelletti, E
Borck, G
Wilson, E
Riordan, GP
Wangemann, P
Forge, A
Steel, KP
Liddle, RA
Friedman, TB
Belyantseva, IA
AF Morozko, Eva L.
Nishio, Ayako
Ingham, Neil J.
Chandra, Rashmi
Fitzgerald, Tracy
Martelletti, Elisa
Borck, Guntram
Wilson, Elizabeth
Riordan, Gavin P.
Wangemann, Philine
Forge, Andrew
Steel, Karen P.
Liddle, Rodger A.
Friedman, Thomas B.
Belyantseva, Inna A.
TI ILDR1 null mice, a model of human deafness DFNB42, show structural
aberrations of tricellular tight junctions and degeneration of auditory
hair cells
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID SYNDROME MOUSE MODEL; INDUCED HEARING-LOSS; STRIA VASCULARIS; KNOCKOUT
MICE; GUINEA-PIG; INTERCELLULAR-JUNCTIONS; FREEZE-FRACTURE; GENOME-WIDE;
PROTEIN; BARRIER
AB In the mammalian inner ear, bicellular and tricellular tight junctions (tTJs) seal the paracellular space between epithelial cells. Tricellulin and immunoglobulin-like (Ig-like) domain containing receptor 1 (ILDR1, also referred to as angulin-2) localize to tTJs of the sensory and non-sensory epithelia in the organ of Corti and vestibular end organs. Recessive mutations of TRIC (DFNB49) encoding tricellulin and ILDR1 (DFNB42) cause human non-syndromic deafness. However, the pathophysiology of DFNB42 deafness remains unknown. ILDR1 was recently reported to be a lipoprotein receptor mediating the secretion of the fat-stimulated cholecystokinin (CCK) hormone in the small intestine, while ILDR1 in EpH4 mouse mammary epithelial cells in vitro was shown to recruit tricellulin to tTJs. Here we show that two different mouse Ildr1 mutant alleles have early-onset severe deafness associated with a rapid degeneration of cochlear hair cells (HCs) but have a normal endocochlear potential. ILDR1 is not required for recruitment of tricellulinto tTJs in the cochlea in vivo; however, tricellulin becomes mislocalized in the inner ear sensory epithelia of ILDR1 null mice after the first postnatal week. As revealed by freeze-fracture electron microscopy, ILDR1 contributes to the ultrastructure of inner ear tTJs. Taken together, our data provide insight into the pathophysiology of human DFNB42 deafness and demonstrate that ILDR1 is crucial for normal hearing by maintaining the structural and functional integrity of tTJs, which are critical for the survival of auditory neurosensory HCs.
C1 [Morozko, Eva L.; Wilson, Elizabeth; Riordan, Gavin P.; Friedman, Thomas B.; Belyantseva, Inna A.] Natl Inst Deafness & Other Commun Disorders, Sect Human Genet, Mouse Auditory Testing Core Facil, NIH, Bethesda, MD 20892 USA.
[Nishio, Ayako] Natl Inst Deafness & Other Commun Disorders, Mol Biol & Genet Sect, Mouse Auditory Testing Core Facil, NIH, Bethesda, MD 20892 USA.
[Fitzgerald, Tracy] Natl Inst Deafness & Other Commun Disorders, Mouse Auditory Testing Core Facil, NIH, Bethesda, MD 20892 USA.
[Ingham, Neil J.; Martelletti, Elisa; Steel, Karen P.] Kings Coll London, Wolfson Ctr Age Related Dis, London SE1 1UL, England.
[Chandra, Rashmi; Liddle, Rodger A.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA.
[Borck, Guntram] Univ Ulm, Inst Human Genet, D-89081 Ulm, Germany.
[Wangemann, Philine] Kansas State Univ, Dept Anat & Physiol, Manhattan, KS 66506 USA.
[Forge, Andrew] UCL, Ctr Auditory Res, London WC1X 8EE, England.
RP Belyantseva, IA (reprint author), Natl Inst Deafness & Other Commun Disorders, NIH, John Edward Porter Neurosci Res Ctr, 35A Convent Dr,Room 1F 141, Bethesda, MD 20892 USA.
EM belyants@nidcd.nih.gov
RI Borck, Guntram/F-1868-2015
FU Wellcome Trust [WT100669MA]; Medical Research Council; Rosetrees Trust;
National Institutes of Health [DK098796, DK091946, NIH-R01-DC012151];
National Institute on Deafness and Other Communication Disorders
Intramural Research Program [DC000060-14, DC000039-18]; NIDCD/NIH
FX This work was supported in part by the Wellcome Trust (WT100669MA to
K.P.S.), the Medical Research Council (to K.P.S.) and the Rosetrees
Trust (A.F.). This work was supported by National Institutes of Health
(DK098796 and DK091946 to R.A.L., NIH-R01-DC012151 to P.W.) and the
National Institute on Deafness and Other Communication Disorders
Intramural Research Program (DC000060-14 to A.N. and DC000039-18 to
T.B.F.). Funding to pay the Open Access publication charges for this
article was provided by the NIDCD/NIH from T.B.F.'s budget.
NR 62
TC 6
Z9 6
U1 1
U2 2
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 FEB 1
PY 2015
VL 24
IS 3
BP 609
EP 624
DI 10.1093/hmg/ddu474
PG 16
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA CC1XE
UT WOS:000350137900002
PM 25217574
ER
PT J
AU Ilyushina, NA
Haynes, BC
Hoen, AG
Khalenkov, AM
Housman, ML
Brown, EP
Ackerman, ME
Treanor, JJ
Luke, CJ
Subbarao, K
Wright, PF
AF Ilyushina, Natalia A.
Haynes, Brenda C.
Hoen, Anne G.
Khalenkov, Alexey M.
Housman, Molly L.
Brown, Eric P.
Ackerman, Margaret E.
Treanor, John J.
Luke, Catherine J.
Subbarao, Kanta
Wright, Peter F.
TI Live Attenuated and Inactivated Influenza Vaccines in Children
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
DE influenza; vaccines; children
ID WILD-TYPE VIRUS; YOUNG-CHILDREN; RESPIRATORY-TRACT; RELATIVE EFFICACY;
TRIVALENT; COLD; ADULTS; RESISTANCE; CHALLENGE; INFECTION
AB Background. Live attenuated influenza vaccine (LAIV) and inactivated influenza vaccine (IIV) are available for children. Local and systemic immunity induced by LAIV followed a month later by LAIV and IIV followed by LAIV were investigated with virus recovery after LAIV doses as surrogates for protection against influenza on natural exposure.
Methods. Fifteen children received IIV followed by LAIV, 13 an initial dose of LAIV, and 11 a second dose of LAIV. The studies were done during autumn 2009 and autumn 2010 with the same seasonal vaccine (A/California/07/09 [H1N1], A/Perth/16/09 [H3N2], B/Brisbane/60/08).
Results. Twenty-eight of 39 possible influenza viral strains were recovered after the initial dose of LAIV. When LAIV followed IIV, 21 of 45 viral strains were identified. When compared to primary LAIV infection, the decreased frequency of shedding with the IIV-LAIV schedule was significant (P = .023). With LAIV-LAIV, the fewest viral strains were recovered (3/33)-numbers significantly lower (P < .001) than shedding after initial LAIV and after IIV-LAIV (P < .001). Serum hemagglutination inhibition antibody responses were more frequent after IIV than LAIV (P = .02). In contrast, more mucosal immunoglobulin A responses were seen with LAIV.
Conclusions. LAIV priming induces greater inhibition of virus recovery on LAIV challenge than IIV priming. The correlate(s) of protection are the subject of ongoing analysis.
C1 [Ilyushina, Natalia A.; Haynes, Brenda C.; Khalenkov, Alexey M.; Wright, Peter F.] Geisel Sch Med Dartmouth, Dept Pediat, Lebanon, NH 03756 USA.
[Hoen, Anne G.] Geisel Sch Med Dartmouth, Dept Commun & Family Med, Lebanon, NH 03756 USA.
[Housman, Molly L.] Geisel Sch Med Dartmouth, Dept Microbiol & Immunol, Lebanon, NH 03756 USA.
[Brown, Eric P.; Ackerman, Margaret E.] Thayer Sch Engn Dartmouth, Hanover, NH USA.
[Treanor, John J.] Univ Rochester, Dept Med, Med Ctr, New York, NY USA.
[Luke, Catherine J.; Subbarao, Kanta] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Wright, PF (reprint author), Geisel Sch Med Dartmouth, Dept Pediat, 1 Med Ctr Dr,Borwell 330 W, Lebanon, NH 03756 USA.
EM peter.f.wright@hitchcock.org
OI Brown, Eric/0000-0002-8438-6136
FU Division of Intramural Research of the NIAID, National Institutes of
Health [HHSN272200900026C]; American Recovery and Reinvestment Act; Bill
& Melinda Gates Foundation [OPP1032817]
FX This work was supported by the Division of Intramural Research of the
NIAID, National Institutes of Health (contract number
HHSN272200900026C); American Recovery and Reinvestment Act funding (to
P. F. W.); and the Bill & Melinda Gates Foundation (grant number
OPP1032817 to M. E. A.).
NR 21
TC 9
Z9 9
U1 0
U2 5
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 FEB 1
PY 2015
VL 211
IS 3
BP 352
EP 360
DI 10.1093/infdis/jiu458
PG 9
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA CC3CG
UT WOS:000350221500004
PM 25165161
ER
PT J
AU Brickley, EB
Wood, AM
Kabyemela, E
Morrison, R
Kurtis, JD
Fried, M
Duffy, PE
AF Brickley, Elizabeth B.
Wood, Angela M.
Kabyemela, Edward
Morrison, Robert
Kurtis, Jonathan D.
Fried, Michal
Duffy, Patrick E.
TI Fetal Origins of Malarial Disease: Cord Blood Cytokines as Risk Markers
for Pediatric Severe Malarial Anemia
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
DE malaria; anemia; cord blood; inflammation; cytokines; developmental
programming; risk marker
ID PLASMODIUM-FALCIPARUM MALARIA; SUSCEPTIBILITY; RESPONSES; CHILDREN;
INTERLEUKIN-10; ERYTHROCYTES; EPIDEMIOLOGY; METAANALYSIS; COINFECTION;
EXPRESSION
AB Background. Severe malarial anemia (SMA) remains a major cause of pediatric illness and mortality in Sub-Saharan Africa. Here we test the hypothesis that prenatal exposures, reflected by soluble inflammatory mediators in cord blood, can condition an individual's susceptibility to SMA.
Methods. In a Tanzanian birth cohort (n = 743), we measured cord blood concentrations of tumor necrosis factor (TNF), TNF receptors I and II (TNF-RI and TNF-RII), interleukin (IL)-1 beta, IL-4, IL-5, IL-6, IL-10, and interferon gamma (IFN-gamma). After adjusting for conventional covariates, we calculated the hazard ratios (HR) for time to first SMA event with log(e) cytokine concentrations dichotomized at the median, by quartile, and per standard deviation (SD) increase.
Results. Low levels of TNF, TNF-RI, IL-1 beta, and IL-5 and high levels of TNF-RII were associated statistically significantly and respectively with approximately 3-fold, 2-fold, 8-fold, 4-fold, and 3-fold increased risks of SMA (Hb < 50 g/L). TNF, TNF-RI, and IL-1 beta concentrations were inversely and log-linearly associated with SMA risk; the HR (95% confidence interval [CI]) per 1-SD increase were respectively 0.81 (.65, 1.02), 0.76 (.62, .92), and 0.50 (.40, .62).
Conclusions. These data suggest that proinflammatory cytokine levels at birth are inversely associated with SMA risk and support the hypothesis that pediatric malarial disease has fetal origins.
C1 [Brickley, Elizabeth B.; Morrison, Robert; Fried, Michal; Duffy, Patrick E.] NIAID, Lab Malaria Immunol & Vaccinol, NIH, Rockville, MD 20852 USA.
[Brickley, Elizabeth B.; Wood, Angela M.] Univ Cambridge, Strangeways Res Labs, Dept Publ Hlth & Primary Care, Cambridge CB2 1TN, England.
[Kabyemela, Edward; Morrison, Robert] Seattle Biomed Res Inst, MOMS Project, Washington, DC USA.
[Kabyemela, Edward] Muheza Designated Dist Hosp, Muheza, Tanzania.
[Kurtis, Jonathan D.] Brown Univ, Dept Pathol & Lab Med, Rhode Isl Hosp, Sch Med, Providence, RI 02912 USA.
RP Duffy, PE (reprint author), NIAID, Lab Malaria Immunol & Vaccinol, NIH, Twinbrook 1,Room 1111,5640 Fishers Ln, Rockville, MD 20852 USA.
EM patrick.duffy@nih.gov
FU Division of Intramural Research, National Institute of Allergy and
Infectious Diseases of the National Institutes of Health; Bill & Melinda
Gates Foundation [29202]; Foundation for NIH through the Grand
Challenges in Global Health Initiative [1364]; National Institutes of
Health Fogarty International Center [D43 TW005509]; National Institutes
of Health [R01 AI52059]
FX This work was supported by the Division of Intramural Research, National
Institute of Allergy and Infectious Diseases of the National Institutes
of Health, the Bill & Melinda Gates Foundation [grant number 29202], the
Foundation for the NIH through the Grand Challenges in Global Health
Initiative [grant 1364], the National Institutes of Health Fogarty
International Center [grant D43 TW005509], and the National Institutes
of Health [grant R01 AI52059], all grants to P. E. D.
NR 32
TC 2
Z9 2
U1 0
U2 5
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 FEB 1
PY 2015
VL 211
IS 3
BP 436
EP 444
DI 10.1093/infdis/jiu454
PG 9
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA CC3CG
UT WOS:000350221500013
PM 25139023
ER
PT J
AU Chen, Y
Yeh, AJ
Cheung, GYC
Villaruz, AE
Tan, VY
Joo, HS
Chatterjee, SS
Yu, YS
Otto, M
AF Chen, Yan
Yeh, Anthony J.
Cheung, Gordon Y. C.
Villaruz, Amer E.
Tan, Vee Y.
Joo, Hwang-Soo
Chatterjee, Som S.
Yu, Yunsong
Otto, Michael
TI Basis of Virulence in a Panton-Valentine Leukocidin-Negative
Community-Associated Methicillin-Resistant Staphylococcus aureus Strain
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
DE alpha-toxin; community-associated infection; methicillin-resistant
Staphylococcus aureus; Panton-Valentine leukocidin; phenol-soluble
modulins
ID PHENOL-SOLUBLE MODULINS; ALPHA-TOXIN; INFECTIONS; NEUTROPHILS; MRSA;
AGR; IDENTIFICATION; DETERMINANTS; PATHOGENESIS; EXPRESSION
AB Community-associated (CA) infections with methicillin-resistant Staphylococcus aureus (MRSA) are on a global rise. However, analysis of virulence characteristics has been limited almost exclusively to the US endemic strain USA300. CA-MRSA strains that do not produce Panton-Valentine leukocidin (PVL) have not been investigated on a molecular level. Therefore, we analyzed virulence determinants in a PVL-negative CA-MRSA strain, ST72, from Korea. Genome-wide analysis identified 3 loci that are unique to that strain, but did not affect virulence. In contrast, phenol-soluble modulins (PSMs) and the global virulence regulator Agr strongly affected lysis of neutrophils and erythrocytes, while alpha-toxin and Agr had a major impact on in vivo virulence. Our findings substantiate the general key roles these factors play in CA-MRSA virulence. However, our analyses also showed noticeable differences to strain USA300, inasmuch as alpha-toxin emerged as a much more important factor than PSMs in experimental skin infection caused by ST72.
C1 [Chen, Yan; Yeh, Anthony J.; Cheung, Gordon Y. C.; Villaruz, Amer E.; Tan, Vee Y.; Joo, Hwang-Soo; Chatterjee, Som S.; Otto, Michael] NIAID, Pathogen Mol Genet Sect, Lab Human Bacterial Pathogenesis, NIH, Bethesda, MD 20892 USA.
[Chen, Yan; Yu, Yunsong] Zhejiang Univ, Coll Med, Sir Run Run Shaw Hosp, Dept Infect Dis, Hangzhou 310003, Zhejiang, Peoples R China.
RP Otto, M (reprint author), NIAID, Lab Human Bacterial Pathogenesis, NIH, Bldg 33,1W10,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM motto@niaid.nih.gov
OI Chen, Yan/0000-0002-7679-1713; Otto, Michael/0000-0002-2222-4115; JOO,
HWANG-SOO/0000-0003-4668-3225
FU National Institute of Allergy and Infectious Diseases [ZIA AI000904-
12]; China Scholarship Council
FX This work was supported by the Intramural Research Program of the
National Institute of Allergy and Infectious Diseases (ZIA AI000904- 12
to M. O.) and the China Scholarship Council (to Y. C.). The authors
thank Yuanjun Zhu for help with neutrophil isolation.
NR 45
TC 6
Z9 6
U1 0
U2 7
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 FEB 1
PY 2015
VL 211
IS 3
BP 472
EP 480
DI 10.1093/infdis/jiu462
PG 9
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA CC3CG
UT WOS:000350221500017
PM 25139021
ER
PT J
AU Luna, B
Kubler, A
Larsson, C
Foster, B
Bagci, U
Mollura, DJ
Jain, SK
Bishai, WR
AF Luna, Brian
Kubler, Andre
Larsson, Christer
Foster, Brent
Bagci, Ulas
Mollura, Daniel J.
Jain, Sanjay K.
Bishai, William R.
TI In Vivo Prediction of Tuberculosis-Associated Cavity Formation in
Rabbits
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
DE CT; [F-18]-FDG; PET; tuberculosis
ID MYCOBACTERIUM-TUBERCULOSIS
AB The presence of cavitary lesions in patients with tuberculosis poses a significant clinical concern due to the risk of infectivity and the risk of antibiotic treatment failure. We describe 2 algorithms that use noninvasive positron emission tomography (PET) and computed tomography (CT) to predict the development of cavitary lesions in rabbits. Analysis of the PET region of interest predicted cavitary disease with 100% sensitivity and 76% specificity, and analysis of the CT region of interest predicted cavitary disease with 83.3% sensitivity and 76.9% specificity. Our results show that restricting our analysis to regions with high [F-18]-fluorodeoxyglucose uptake provided the best combination of sensitivity and specificity.
C1 [Luna, Brian; Kubler, Andre; Larsson, Christer; Jain, Sanjay K.; Bishai, William R.] Johns Hopkins Univ, Sch Med, Johns Hopkins Ctr TB Res, Baltimore, MD USA.
[Jain, Sanjay K.; Bishai, William R.] Johns Hopkins Univ, Sch Med, Ctr Infect & Inflammat Imaging Res, Baltimore, MD USA.
[Jain, Sanjay K.] Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21205 USA.
[Foster, Brent; Bagci, Ulas; Mollura, Daniel J.] NIH, Ctr Infect Dis Imaging, Dept Radiol & Imaging Sci, Bethesda, MD 20892 USA.
[Bishai, William R.] Howard Hughes Med Inst, Chevy Chase, MD USA.
[Kubler, Andre] Univ London Imperial Coll Sci Technol & Med, Dept Med, London SW7 2AZ, England.
RP Bishai, WR (reprint author), Johns Hopkins Sch Med, Johns Hopkins Ctr TB Res, 1550 Orleans,CRB2 St,Ste 103, Baltimore, MD 21231 USA.
EM wbishai@jhmi.edu
OI Larsson, Christer/0000-0002-5714-924X; Bagci, Ulas/0000-0001-7379-6829;
Luna, PhD, Brian/0000-0001-6718-4551
FU Swedish Research Council; Swedish Society for Medical Research; National
Institute of Allergy and Infectious Diseases [RO1AI079590]; National
Institutes of Health [RO1A1035272]; Howard Hughes Medical Institute
FX This work was supported by the Swedish Research Council, the Swedish
Society for Medical Research, the National Institute of Allergy and
Infectious Diseases (grant RO1AI079590), the National Institutes of
Health (grant RO1A1035272), and the Howard Hughes Medical Institute.
NR 15
TC 2
Z9 2
U1 0
U2 2
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0022-1899
EI 1537-6613
J9 J INFECT DIS
JI J. Infect. Dis.
PD FEB 1
PY 2015
VL 211
IS 3
BP 481
EP 485
DI 10.1093/infdis/jiu449
PG 5
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA CC3CG
UT WOS:000350221500018
PM 25117755
ER
PT J
AU Barnhill, A
Miller, FG
AF Barnhill, Anne
Miller, Franklin G.
TI Placebo and Deception: A Commentary
SO JOURNAL OF MEDICINE AND PHILOSOPHY
LA English
DT Article
DE deception; ethics; manipulation; placebo treatment
ID CLINICAL-PRACTICE; ETHICS
AB In a recent article in this Journal, Shlomo Cohen and Haim Shapiro (2013) introduce the concept of "comparable placebo treatments" (CPTs)-placebo treatments with biological effects similar to the drugs they replace-and argue that doctors are not being deceptive when they prescribe or administer CPTs without revealing that they are placebos. We critique two of Cohen and Shapiro's primary arguments. First, Cohen and Shapiro argue that offering undisclosed placebos is not lying to the patient, but rather is making a self-fulfilling prophecy-telling a "lie" that, ideally, will become true. We argue that offering undisclosed placebos is not a "lie" but is a straightforward case of deceptively misleading the patient. Second, Cohen and Shapiro argue that offering undisclosed CPTs is not equivocation. We argue that it typically is equivocation or deception of another sort. If justifiable, undisclosed placebo use will have to be justified as a practice that is deceptive in most instances.
C1 [Barnhill, Anne] Univ Penn, Philadelphia, PA 19104 USA.
[Miller, Franklin G.] NIH, Bethesda, MD 20892 USA.
RP Barnhill, A (reprint author), Univ Penn, Dept Med Eth & Hlth Policy, 3401 Market St,Suite 320, Philadelphia, PA 19104 USA.
EM anne.barnhill@gmail.com
NR 15
TC 4
Z9 4
U1 1
U2 2
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 FEB
PY 2015
VL 40
IS 1
BP 69
EP 82
DI 10.1093/jmp/jhu043
PG 14
WC Ethics; Social Sciences, Biomedical
SC Social Sciences - Other Topics; Biomedical Social Sciences
GA CC3FK
UT WOS:000350231500005
PM 25503605
ER
PT J
AU Zhang, F
Xu, LY
Xu, LX
Xu, Q
Li, DS
Yang, YZ
Karsenty, G
Chen, CD
AF Zhang, Feng
Xu, Longyong
Xu, Longxia
Xu, Qing
Li, Dangsheng
Yang, Yingzi
Karsenty, Gerard
Chen, Charlie Degui
TI JMJD3 promotes chondrocyte proliferation and hypertrophy during
endochondral bone formation in mice
SO JOURNAL OF MOLECULAR CELL BIOLOGY
LA English
DT Article
DE JMJD3; RUNX2; chondrocyte; endochondral bone formation
ID EMBRYONIC STEM-CELLS; HISTONE LYSINE METHYLATION; DEMETHYLASE JMJD3;
H3K27 DEMETHYLASE; GENE-EXPRESSION; METHYLTRANSFERASE ACTIVITY;
DEVELOPMENTAL REGULATORS; CBFA1-DEFICIENT MICE; INDIAN-HEDGEHOG; GROWTH
PLATES
AB JMJD3 (KDM6B) is an H3K27me3 demethylase and counteracts polycomb-mediated transcription repression. However, the function of JMJD3 in vivo is not well understood. Here we show that JMJD3 is highly expressed in cells of the chondrocyte lineage, especially in prehypertrophic and hypertrophic chondrocytes, during endochondral ossification. Homozygous deletion of Jmjd3 results in severely decreased proliferation and delayed hypertrophy of chondrocytes, and thereby marked retardation of endochondral ossification in mice. Genetically, JMJD3 associates with RUNX2 to promote proliferation and hypertrophy of chondrocytes. Biochemically, JMJD3 associates with and enhances RUNX2 activity by derepression of Runx2 and Ihh transcription through its H3K27me3 demethylase activity. These results demonstrate that JMJD3 is a key epigenetic regulator in the process of cartilage maturation during endochondral bone formation.
C1 [Zhang, Feng; Xu, Longyong; Xu, Longxia; Xu, Qing; Chen, Charlie Degui] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, State Key Lab Mol Biol,Shanghai Key Lab Mol Andro, Shanghai 200031, Peoples R China.
[Zhang, Feng] Fourth Mil Med Univ, Xijing Hosp, Dept Pathol, State Key Lab Canc Biol, Xian 710032, Shaanxi, Peoples R China.
[Li, Dangsheng] Chinese Acad Sci, Shanghai Inst Biol Sci, Shanghai Informat Ctr Life Sci, Shanghai 200031, Peoples R China.
[Yang, Yingzi] NHGRI, NIH, Bethesda, MD 20892 USA.
[Karsenty, Gerard] Columbia Univ, Coll Phys & Surg, Dept Genet & Dev, New York, NY 10032 USA.
RP Chen, CD (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, State Key Lab Mol Biol,Shanghai Key Lab Mol Andro, Shanghai 200031, Peoples R China.
EM cdchen@sibcb.ac.cn
FU National Natural Science Foundation of China [91219304]; National Basic
Research Program of China [2010CB529705, 2011CB510103, 2014CB943100];
Council of Shanghai Municipal Government for Science and Technology
FX This work was supported by the National Natural Science Foundation of
China (91219304), National Basic Research Program of China
(2010CB529705, 2011CB510103, 2014CB943100), and the Council of Shanghai
Municipal Government for Science and Technology.
NR 52
TC 10
Z9 12
U1 3
U2 11
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1674-2788
EI 1759-4685
J9 J MOL CELL BIOL
JI J. Mol. Cell Biol.
PD FEB
PY 2015
VL 7
IS 1
BP 23
EP 34
DI 10.1093/jmcb/mjv003
PG 12
WC Cell Biology
SC Cell Biology
GA CC3EO
UT WOS:000350228600004
PM 25587042
ER
PT J
AU Ma, J
Pawar, RS
Grundel, E
Mazzola, EP
Ridge, CD
Masaoka, T
Le Grice, SFJ
Wilson, J
Beutler, JA
Krynitsky, AJ
AF Ma, Jun
Pawar, Rahul S.
Grundel, Erich
Mazzola, Eugene P.
Ridge, Clark D.
Masaoka, Takashi
Le Grice, Stuart F. J.
Wilson, Jennifer
Beutler, John A.
Krynitsky, Alexander J.
TI Sesquiterpenoid Tropolone Glycosides from Liriosma ovata
SO JOURNAL OF NATURAL PRODUCTS
LA English
DT Article
ID RIBONUCLEASE-H ACTIVITY; DULACIA-GUIANENSIS; MANICOL; ASSAY
AB Two new sesquiterpenoid tropolone glycosides, liriosmasides A (1) and B (2), along with two known compounds, secoxyloganin and oplopanpheside C, were isolated from a methanol extract of the roots of Liriosma ovata. The structures of 1 and 2 were elucidated by spectroscopic methods including 1D and 2D NMR and by high-resolution mass spectrometry involving an ultra-high-performance liquid chromatography-quadrupole-orbital ion trap mass spectrometric (UHPLC-Q-Orbitrap MS) method. Compound 1 showed weak inhibitory activity against HIV RNase H.
C1 [Ma, Jun; Pawar, Rahul S.; Grundel, Erich; Mazzola, Eugene P.; Ridge, Clark D.; Krynitsky, Alexander J.] US FDA, Ctr Food Safety & Appl Nutr, Off Regulatory Sci, College Pk, MD 20740 USA.
[Masaoka, Takashi; Le Grice, Stuart F. J.] Natl Canc Inst, HIV Drug Resistance Program, RT Biochem Sect, Frederick, MD 21702 USA.
[Wilson, Jennifer; Beutler, John A.] Natl Canc Inst, Ctr Canc Res, Mol Targets Lab, Frederick, MD 21702 USA.
RP Ma, J (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Regulatory Sci, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA.
EM jun.ma@fda.hhs.gov
NR 17
TC 1
Z9 1
U1 1
U2 14
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0163-3864
EI 1520-6025
J9 J NAT PROD
JI J. Nat. Prod.
PD FEB
PY 2015
VL 78
IS 2
BP 315
EP 319
DI 10.1021/np5006696
PG 5
WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy
SC Plant Sciences; Pharmacology & Pharmacy
GA CC4MX
UT WOS:000350328600021
PM 25587934
ER
PT J
AU Wu, F
Ourmanov, I
Riddick, N
Matsuda, K
Whitted, S
Plishka, RJ
Buckler-White, A
Starost, MF
Hirsch, VM
AF Wu, Fan
Ourmanov, Ilnour
Riddick, Nadeene
Matsuda, Kenta
Whitted, Sonya
Plishka, Ronald J.
Buckler-White, Alicia
Starost, Matthew F.
Hirsch, Vanessa M.
TI TRIM5 alpha Restriction Affects Clinical Outcome and Disease Progression
in Simian Immunodeficiency Virus-Infected Rhesus Macaques
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID ZINC-FINGER NUCLEASES; HIV-1 INFECTION; ANTIRETROVIRAL THERAPY;
IN-VITRO; T-CELLS; RESISTANCE; TRIM5; GENE; NEUTRALIZATION;
POLYMORPHISMS
AB Tripartite motif-containing protein 5 alpha (TRIM5 alpha) is considered to be a potential target for cell-based gene modification therapy against human immunodeficiency virus type 1 (HIV-1) infection. In the present study, we used a relevant rhesus macaque model of infection with simian immunodeficiency virus from sooty mangabey (SIVsm) to evaluate the effect of TRIM5 alpha restriction on clinical outcome. For macaques expressing a restrictive TRIM5 genotype, the disease outcomes of those infected with the wildtype TRIM-sensitive SIVsm strain and those infected with a virus with escape mutations in the capsid were compared. We found that TRIM5 alpha restriction significantly delayed disease progression and improved the survival rate of SIV-infected macaques, supporting the feasibility of exploiting TRIM5 alpha as a target for gene therapy against HIV-1. Furthermore, we also found that preservation of memory CD4T cells was associated with protection by TRIM5 alpha restriction, suggesting memory CD4 T cells or their progenitor cells as an ideal target for gene modification. Despite the significant effect of TRIM5 alpha restriction on survival, SIV escape from TRIM5 alpha restriction was also observed; therefore, this may not be an effective stand-alone strategy and may require combination with other targets.
IMPORTANCE
Recent studies suggest that it may be feasible not only to suppress viral replication with antiviral drugs but also potentially to eliminate or "cure" human immunodeficiency virus (HIV) infection. One approach being explored is the use of gene therapy to introduce genes that can restrict HIV replication, including a restrictive version of the host factor TRIM5 alpha. TRIM5 was identified as a factor that restricts HIV replication in macaque cells. The rhesus gene is polymorphic, and some alleles are restrictive for primary SIVsm isolates, although escape mutations arise late in infection. Introduction of these escape mutations into the parental virus conferred resistance to TRIM5 on macaques. The present study evaluated these animals for long-term outcomes and found that TRIM5 alpha restriction significantly delayed disease progression and improved the survival rate of SIV-infected macaques, suggesting that this could be a valid gene therapy approach that could be adapted for HIV.
C1 [Wu, Fan; Ourmanov, Ilnour; Riddick, Nadeene; Matsuda, Kenta; Whitted, Sonya; Plishka, Ronald J.; Buckler-White, Alicia; Hirsch, Vanessa M.] NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA.
[Starost, Matthew F.] NIH, Div Vet Resources, OD, ORS, Bethesda, MD 20892 USA.
RP Hirsch, VM (reprint author), NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA.
EM vhirsch@niaid.nih.gov
FU federal funds from the intramural program of the National Institute of
Allergy and Infectious Diseases, National Institutes of Health
FX This work was supported with federal funds from the intramural program
of the National Institute of Allergy and Infectious Diseases, National
Institutes of Health.
NR 42
TC 5
Z9 5
U1 0
U2 8
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 FEB
PY 2015
VL 89
IS 4
BP 2233
EP 2240
DI 10.1128/JVI.02978-14
PG 8
WC Virology
SC Virology
GA AZ9UT
UT WOS:000348562800027
PM 25473059
ER
PT J
AU Carroll, JA
Striebel, JF
Race, B
Phillips, K
Chesebro, B
AF Carroll, James A.
Striebel, James F.
Race, Brent
Phillips, Katie
Chesebro, Bruce
TI Prion Infection of Mouse Brain Reveals Multiple New Upregulated Genes
Involved in Neuroinflammation or Signal Transduction
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID NF-KAPPA-B; NECROSIS-FACTOR-ALPHA; ACUTE-PHASE RESPONSE; INTERLEUKIN-1
RECEPTOR ANTAGONIST; CREUTZFELDT-JAKOB-DISEASE; INTERFERON-GAMMA;
NERVOUS-SYSTEM; CELL-DEATH; SPONGIFORM ENCEPHALOPATHIES; TRANSCRIPTIONAL
ACTIVATION
AB Gliosis is often a preclinical pathological finding in neurodegenerative diseases, including prion diseases, but the mechanisms facilitating gliosis and neuronal damage in these diseases are not understood. To expand our knowledge of the neuroinflammatory response in prion diseases, we assessed the expression of key genes and proteins involved in the inflammatory response and signal transduction in mouse brain at various times after scrapie infection. In brains of scrapie-infected mice at pre- and post-clinical stages, we identified 15 previously unreported differentially expressed genes related to inflammation or activation of the STAT signal transduction pathway. Levels for the majority of differentially expressed genes increased with time postinfection. In quantitative immunoblotting experiments of STAT proteins, STAT1 alpha, phosphorylated-STAT1 alpha (pSTAT1 alpha), and pSTAT3 were increased between 94 and 131 days postinfection (p.i.) in brains of mice infected with strain 22L. Furthermore, a select group of STAT-associated genes was increased preclinically during scrapie infection, suggesting early activation of the STAT signal transduction pathway. Comparison of inflammatory markers between mice infected with scrapie strains 22L and RML indicated that the inflammatory responses and gene expression profiles in the brains were strikingly similar, even though these scrapie strains infect different brain regions. The endogenous interleukin-1 receptor antagonist (IL-1Ra), an inflammatory marker, was newly identified as increasing preclinically in our model and therefore might influence scrapie pathogenesis in vivo. However, in IL-1Ra-deficient or overexpressor transgenic mice inoculated with scrapie, neither loss nor overexpression of IL-1Ra demonstrated any observable effect on gliosis, protease-resistant prion protein (PrPres) formation, disease tempo, pathology, or expression of the inflammatory genes analyzed.
IMPORTANCE
Prion infection leads to PrPres deposition, gliosis, and neuroinflammation in the central nervous system before signs of clinical illness. Using a scrapie mouse model of prion disease to assess various time points postinoculation, we identified 15 unreported genes that were increased in the brains of scrapie-infected mice and were associated with inflammation and/or JAK-STAT activation. Comparison of mice infected with two scrapie strains (22L and RML), which have dissimilar neuropathologies, indicated that the inflammatory responses and gene expression profiles in the brains were similar. Genes that increased prior to clinical signs might be involved in controlling scrapie infection or in facilitating damage to host tissues. We tested the possible role of the endogenous IL-1Ra, which was increased at 70 days p.i. In scrapie-infected mice deficient in or overexpressing IL-1Ra, there was no observable effect on gliosis, PrPres formation, disease tempo, pathology, or expression of inflammatory genes analyzed.
C1 [Carroll, James A.; Striebel, James F.; Race, Brent; Phillips, Katie; Chesebro, Bruce] NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA.
RP Carroll, JA (reprint author), NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA.
EM carrollja2@niaid.nih.gov
FU National Institute of Allergy and Infectious Diseases, Division of
Intramural Research
FX This work was supported by the National Institute of Allergy and
Infectious Diseases, Division of Intramural Research.
NR 95
TC 4
Z9 4
U1 0
U2 3
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
EI 1098-5514
J9 J VIROL
JI J. Virol.
PD FEB
PY 2015
VL 89
IS 4
BP 2388
EP 2404
DI 10.1128/JVI.02952-14
PG 17
WC Virology
SC Virology
GA AZ9UT
UT WOS:000348562800040
PM 25505076
ER
PT J
AU Evans, CM
Raclawska, DS
Ttofali, F
Liptzin, DR
Fletcher, AA
Harper, DN
McGing, MA
McElwee, MM
Williams, OW
Sanchez, E
Roy, MG
Kindrachuk, KN
Wynn, TA
Eltzschig, HK
Blackburn, MR
Tuvim, MJ
Janssen, WJ
Schwartz, DA
Dickey, BF
AF Evans, Christopher M.
Raclawska, Dorota S.
Ttofali, Fani
Liptzin, Deborah R.
Fletcher, Ashley A.
Harper, Daniel N.
McGing, Maggie A.
McElwee, Melissa M.
Williams, Olatunji W.
Sanchez, Elizabeth
Roy, Michelle G.
Kindrachuk, Kristen N.
Wynn, Thomas A.
Eltzschig, Holger K.
Blackburn, Michael R.
Tuvim, Michael J.
Janssen, William J.
Schwartz, David A.
Dickey, Burton F.
TI The polymeric mucin Muc5ac is required for allergic airway
hyperreactivity
SO NATURE COMMUNICATIONS
LA English
DT Article
ID GOBLET CELL HYPERPLASIA; GROWTH-FACTOR RECEPTOR; SMOOTH-MUSCLE;
N-ACETYLCYSTEINE; MUCOCILIARY CLEARANCE; MUCOUS METAPLASIA; MUCUS
PRODUCTION; CYSTIC-FIBROSIS; CHALLENGED MICE; ACUTE ASTHMA
AB In asthma, airflow obstruction is thought to result primarily from inflammation-triggered airway smooth muscle (ASM) contraction. However, anti-inflammatory and smooth muscle-relaxing treatments are often temporary or ineffective. Overproduction of the mucin MUC5AC is an additional disease feature that, while strongly associated pathologically, is poorly understood functionally. Here we show that Muc5ac is a central effector of allergic inflammation that is required for airway hyperreactivity (AHR) to methacholine (MCh). In mice bred on two well-characterized strain backgrounds (C57BL/6 and BALB/c) and exposed to two separate allergic stimuli (ovalbumin and Aspergillus extract), genetic removal of Muc5ac abolishes AHR. Residual MCh responses are identical to unchallenged controls, and although inflammation remains intact, heterogeneous mucous occlusion decreases by 74%. Thus, whereas inflammatory effects on ASM alone are insufficient for AHR, Muc5ac-mediated plugging is an essential mechanism. Inhibiting MUC5AC may be effective for treating asthma and other lung diseases where it is also overproduced.
C1 [Evans, Christopher M.; Raclawska, Dorota S.; Ttofali, Fani; Fletcher, Ashley A.; Harper, Daniel N.; McGing, Maggie A.; Janssen, William J.; Schwartz, David A.] Univ Colorado, Sch Med, Dept Med, Aurora, CO 80045 USA.
[Liptzin, Deborah R.] Univ Colorado, Sch Med, Dept Pediat, Aurora, CO 80045 USA.
[McElwee, Melissa M.; Sanchez, Elizabeth; Roy, Michelle G.; Tuvim, Michael J.; Dickey, Burton F.] Univ Texas MD Anderson Canc Ctr, Dept Pulm Med, Houston, TX 77030 USA.
[Williams, Olatunji W.] Peyton Manning Childrens Hosp, Pediat, Indianapolis, IN 46260 USA.
[Kindrachuk, Kristen N.; Wynn, Thomas A.] NIAID, Immunopathogenesis Sect, Program Barrier Immun & Repair, Bethesda, MD 20892 USA.
[Eltzschig, Holger K.] Univ Colorado, Sch Med, Dept Anesthesiol, Aurora, CO 80045 USA.
[Blackburn, Michael R.] Univ Texas Houston, Dept Biochem & Mol Biol, Houston, TX 77030 USA.
[Janssen, William J.] Natl Jewish Hlth, Dept Med, Denver, CO 80206 USA.
RP Evans, CM (reprint author), Univ Colorado, Sch Med, Dept Med, 12700 E 19th Ave,Mailstop 8611,Res Complex 2, Aurora, CO 80045 USA.
EM Christopher.Evans@ucdenver.edu
OI Liptzin, Deborah/0000-0002-3667-1856; Blackburn,
Michael/0000-0002-1394-9966
FU National Institutes of Health [R01HL080396, R21ES023384, R21HL120770,
UH2HL123442, R01HL097000, R01HL070952, R01DK097075, R01HL092188,
R01HL098294, R01HL119837, P01HL114457, R01HL109517]; American Heart
Association [14GRNT19990040]; Crohn's and Colitis Foundation of America;
intramural research program at the National Institute of Allergy and
Infectious Diseases/National Institutes of Health; National Institutes
of Health Cancer Center [P30CA016672]; University of Colorado
[P30CA046934]
FX We thank G. Francis, F. Benavides and J. Parker-Thornburg for their
assistance in generating mutant and congenic mice. Discussions with Dr
W. M. Foster of the Duke University Medical Center were helpful in the
design of our aerosol system. This work was supported by the National
Institutes of Health Grants R01HL080396 and R21ES023384 (C.M.E.);
R21HL120770 (D.A.S.); UH2HL123442 (C.M.E. and D.A.S.); R01HL097000
(B.F.D.); R01HL070952 (M.R.B.); R01DK097075, R01HL092188, R01HL098294
and R01HL119837 (H.K.E.); P01HL114457 (M.R.B. and H.K.E.); R01HL109517
(W.J.J.); and grants by the American Heart Association 14GRNT19990040
(C.M.E.) and the Crohn's and Colitis Foundation of America (H.K.E.).
T.A.W. was supported by the intramural research program at the National
Institute of Allergy and Infectious Diseases/National Institutes of
Health. Additional support was provided by National Institutes of Health
Cancer Center Support Grants P30CA016672 (M.D. Anderson Cancer Center,
including the Research Animal Support Facility-Smithville, Animal
Genetics Services) and P30CA046934 (University of Colorado).
NR 67
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U1 3
U2 8
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 FEB
PY 2015
VL 6
AR 6281
DI 10.1038/ncomms7281
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CC3ZH
UT WOS:000350289500012
PM 25687754
ER
PT J
AU Gao, YD
Yang, P
Shen, HM
Yu, H
Song, XM
Zhang, LY
Zhang, P
Cheng, HZ
Xie, ZJ
Hao, S
Dong, F
Ma, SH
Ji, Q
Bartlow, P
Ding, YH
Wang, LR
Liu, HB
Li, YX
Cheng, H
Miao, WM
Yuan, WP
Yuan, YZ
Cheng, T
Xie, XQ
AF Gao, Yingdai
Yang, Peng
Shen, Hongmei
Yu, Hui
Song, Xianmin
Zhang, Liyan
Zhang, Peng
Cheng, Haizi
Xie, Zhaojun
Hao, Sha
Dong, Fang
Ma, Shihui
Ji, Qing
Bartlow, Patrick
Ding, Yahui
Wang, Lirong
Liu, Haibin
Li, Yanxin
Cheng, Hui
Miao, Weimin
Yuan, Weiping
Yuan, Youzhong
Cheng, Tao
Xie, Xiang-Qun
TI Small-molecule inhibitors targeting INK4 protein p18(INK4C) enhance ex
vivo expansion of haematopoietic stem cells
SO NATURE COMMUNICATIONS
LA English
DT Article
ID SELF-RENEWAL; PROGENITOR CELLS; MAINTENANCE; RECEPTOR; DIFFERENTIATION;
RESPONSIVENESS; PROLIFERATION; REPOPULATION; QUIESCENCE; P27(KIP1)
AB Among cyclin-dependent kinase inhibitors that control the G1 phase in cell cycle, only p18 and p27 can negatively regulate haematopoietic stem cell (HSC) self-renewal. In this manuscript, we demonstrate that p18 protein is a more potent inhibitor of HSC self-renewal than p27 in mouse models and its deficiency promoted HSC expansion in long-term culture. Single-cell analysis indicated that deleting p18 gene favoured self-renewing division of HSC in vitro. Based on the structure of p18 protein and in-silico screening, we further identified novel small-molecule inhibitors that can specifically block the activity of p18 protein. Our selected lead compounds were able to expand functional HSCs in a short-term culture. Thus, these putative small-molecule inhibitors for p18 protein are valuable for further dissecting the signalling pathways of stem cell self-renewal and may help develop more effective chemical agents for therapeutic expansion of HSC.
C1 [Gao, Yingdai; Zhang, Liyan; Hao, Sha; Dong, Fang; Ma, Shihui; Ji, Qing; Ding, Yahui; Li, Yanxin; Cheng, Hui; Miao, Weimin; Yuan, Weiping; Yuan, Youzhong; Cheng, Tao] Chinese Acad Med Sci, Inst Hematol, State Key Lab Expt Hematol, Tianjin 300020, Peoples R China.
[Gao, Yingdai; Zhang, Liyan; Hao, Sha; Dong, Fang; Ma, Shihui; Ji, Qing; Ding, Yahui; Li, Yanxin; Cheng, Hui; Miao, Weimin; Yuan, Weiping; Yuan, Youzhong; Cheng, Tao] Chinese Acad Med Sci, Blood Dis Hosp, Ctr Stem Cell Med, Tianjin 300020, Peoples R China.
[Gao, Yingdai; Zhang, Liyan; Hao, Sha; Dong, Fang; Ma, Shihui; Ji, Qing; Ding, Yahui; Li, Yanxin; Cheng, Hui; Miao, Weimin; Yuan, Weiping; Yuan, Youzhong; Cheng, Tao] Peking Union Med Coll, Tianjin 300020, Peoples R China.
[Yang, Peng; Zhang, Peng; Cheng, Haizi; Xie, Zhaojun; Bartlow, Patrick; Wang, Lirong; Liu, Haibin; Xie, Xiang-Qun] Drug Discovery Inst, Dept Pharmaceut Sci, Computat Chem Genom Screening Ctr, Sch Pharm,Natl Ctr Excellence Drug Abuse Res,NIH, Pittsburgh, PA 15260 USA.
[Yang, Peng; Zhang, Peng; Cheng, Haizi; Xie, Zhaojun; Bartlow, Patrick; Wang, Lirong; Liu, Haibin; Xie, Xiang-Qun] Univ Pittsburgh, Dept Computat & Syst Biol, Pittsburgh, PA 15260 USA.
[Shen, Hongmei; Yu, Hui] Univ Pittsburgh, Sch Med, Dept Radiat Oncol, Pittsburgh, PA 15260 USA.
[Shen, Hongmei; Yu, Hui] Univ Pittsburgh, Inst Canc, Pittsburgh, PA 15260 USA.
[Song, Xianmin] Secondary Mil Med Univ, Changhai Hosp, Dept Hematol, Shanghai 200433, Peoples R China.
RP Cheng, T (reprint author), Chinese Acad Med Sci, Inst Hematol, State Key Lab Expt Hematol, Tianjin 300020, Peoples R China.
EM chengtao@ihcams.ac.cn; xix15@pitt.edu
OI Zhang, Peng/0000-0001-5574-0899
FU National Basic Research Program of China [2011CB964800, 2012CB966600];
National Natural Science Foundation of China (NSFC) [90913018, 81090410,
81421002, 30825017, 81170465]; key technologies R&D Program of Tianjin
[13RCGFSF19500]; NIH [R21HL1096541]
FX This work was funded by the National Basic Research Program of China
(NO. 2011CB964800, 2012CB966600), the National Natural Science
Foundation of China (NSFC 90913018, 81090410, 81421002, 30825017 and
81170465), the key technologies R&D Program of Tianjin (13RCGFSF19500)
and NIH R21HL1096541.
NR 37
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U1 5
U2 33
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 FEB
PY 2015
VL 6
AR 6328
DI 10.1038/ncomms7328
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CC3ZZ
UT WOS:000350291300004
PM 25692908
ER
PT J
AU Alexander, BM
Galanis, E
Yung, WKA
Ballman, KV
Boyett, JM
Cloughesy, TF
Degroot, JF
Huse, JT
Mann, B
Mason, W
Mellinghoff, IK
Mikkelsen, T
Mischel, PS
O'Neill, BP
Prados, MD
Sarkaria, JN
Tawab-Amiri, A
Trippa, L
Ye, XB
Ligon, KL
Berry, DA
Wen, PY
AF Alexander, Brian M.
Galanis, Evanthia
Yung, W. K. Alfred
Ballman, Karla V.
Boyett, James M.
Cloughesy, Timothy F.
Degroot, John F.
Huse, Jason T.
Mann, Bhupinder
Mason, Warren
Mellinghoff, Ingo K.
Mikkelsen, Tom
Mischel, Paul S.
O'Neill, Brian P.
Prados, Michael D.
Sarkaria, Jann N.
Tawab-Amiri, Abdul
Trippa, Lorenzo
Ye, Xiaobu
Ligon, Keith L.
Berry, Donald A.
Wen, Patrick Y.
TI Brain Malignancy Steering Committee clinical trials planning workshop:
Report from the Targeted Therapies Working Group
SO NEURO-ONCOLOGY
LA English
DT Article
DE adaptive randomization; biomarkers; clinical trials; glioblastoma
ID NEWLY-DIAGNOSED GLIOBLASTOMA; PROGRESSION-FREE SURVIVAL; INTEGRATED
GENOMIC ANALYSIS; RANDOMIZED PHASE-III; I-SPY 2; ISOCITRATE
DEHYDROGENASE; ADAPTIVE RANDOMIZATION; ADJUVANT TEMOZOLOMIDE; MUTATIONAL
ANALYSIS; TUMOR SAMPLES
AB Glioblastoma is the most common primary brain malignancy and is associated with poor prognosis despite aggressive local and systemic therapy, which is related to a paucity of viable treatment options in both the newly diagnosed and recurrent settings. Even so, the rapidly increasing number of targeted therapies being evaluated in oncology clinical trials offers hope for the future. Given the broad range of possibilities for future trials, the Brain Malignancy Steering Committee convened a clinical trials planning meeting that was held at the Udvar-Hazy Center in Chantilly, Virginia, on September 19 and 20, 2013. This manuscript reports the deliberations leading up to the event from the Targeted Therapies Working Group and the results of the meeting.
C1 [Alexander, Brian M.; Trippa, Lorenzo; Ligon, Keith L.; Wen, Patrick Y.] Dana Farber Brigham & Womens Canc Ctr, Boston, MA USA.
[Galanis, Evanthia; Ballman, Karla V.; O'Neill, Brian P.; Sarkaria, Jann N.] Mayo Clin, Rochester, MN USA.
[Yung, W. K. Alfred; Degroot, John F.; Berry, Donald A.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Boyett, James M.] St Jude Childrens Res Hosp, Memphis, TN 38105 USA.
[Cloughesy, Timothy F.] Univ Calif Los Angeles, Los Angeles, CA USA.
[Huse, Jason T.; Mellinghoff, Ingo K.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
[Mann, Bhupinder; Tawab-Amiri, Abdul] Natl Canc Inst, Bethesda, MD USA.
[Mason, Warren] Princess Margaret Canc Ctr, Toronto, ON, Canada.
[Mikkelsen, Tom] Henry Ford Hosp, Detroit, MI 48202 USA.
[Mischel, Paul S.] Univ Calif San Diego, San Diego, CA 92103 USA.
[Prados, Michael D.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Ye, Xiaobu] Johns Hopkins Univ, Baltimore, MD USA.
RP Alexander, BM (reprint author), Harvard Univ, Sch Med, Dana Farber Brigham & Womens Canc Ctr, Dept Radiat Oncol, 450 Brookline Ave, Boston, MA 02215 USA.
EM brian_alexander@dfci.harvard.edu
FU Pfizer; Novartis; Genentech; Basilea; Sanofi; Merck; EMD Serono
FX WM reports advisory role for Roche, Lilly and Merck. TM reports advisory
board role for Roche, Merck, and Celgene. MDP reports advisory board
role for Roche and Novartis and clinical and laboratory research support
from Pfizer and Novartis. JNS reports research funding from Genentech,
Basilea, Sanofi, and Merck. KLL reports consulting fee from EMD Serono.
DAB is co-owner of and statistical consultant with Berry Consultants,
LLC, a company that designs Bayesian adaptive clinical trials for
pharmaceutical and medical device companies and NIH cooperative groups.
NR 47
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U1 1
U2 3
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1522-8517
EI 1523-5866
J9 NEURO-ONCOLOGY
JI Neuro-Oncology
PD FEB
PY 2015
VL 17
IS 2
BP 180
EP 188
DI 10.1093/neuonc/nou154
PG 9
WC Oncology; Clinical Neurology
SC Oncology; Neurosciences & Neurology
GA CC1XK
UT WOS:000350138500003
PM 25165194
ER
PT J
AU Morikawa, A
Peereboom, DM
Thorsheim, HR
Samala, R
Balyan, R
Murphy, CG
Lockman, PR
Simmons, A
Weil, RJ
Tabar, V
Steeg, PS
Smith, QR
Seidman, AD
AF Morikawa, Aki
Peereboom, David M.
Thorsheim, Helen R.
Samala, Ramakrishna
Balyan, Rajiv
Murphy, Conleth G.
Lockman, Paul R.
Simmons, Ahkeem
Weil, Robert J.
Tabar, Viviane
Steeg, Patricia S.
Smith, Quentin R.
Seidman, Andrew D.
TI Capecitabine and lapatinib uptake in surgically resected brain
metastases from metastatic breast cancer patients: a prospective study
SO NEURO-ONCOLOGY
LA English
DT Article
DE blood-tumor barrier; brain metastases; breast cancer; capecitabine;
lapatinib
ID TYROSINE KINASE INHIBITOR; RESISTANCE PROTEIN ABCG2; P-GLYCOPROTEIN
ABCB1; CNS METASTASES; LUNG-CANCER; PHASE-II; IN-VITRO; TISSUE; BARRIER;
GROWTH
AB Background. Breast cancer brain metastases (BCBM) are challenging complications that respond poorly to systemic therapy. The role of the blood-tumor barrier in limiting BCBM drug delivery and efficacy has been debated. Herein, we determined tissue and serum levels of capecitabine, its prodrug metabolites, and lapatinib in women with BCBM resected via medically indicated craniotomy.
Methods. Study patients with BCBM requiring surgical resection received either single-dose capecitabine (1250 mg/m(2)) 2-3 h before surgery or 2-5 doses of lapatinib (1250 mg) daily, the last dose 2-3 h before surgery. Serum samples were collected serially on the day of surgery. Drug concentrations were determined in serum and BCBM using liquid chromatography tandem mass spectrometry.
Results. Twelve patients were enrolled: 8 for capecitabine and 4 for lapatinib. Measurable drug levels of capecitabine and metabolites, 5'-deoxy-5-fluorocytidine, 5'-deoxy-5-fluorouridine, and 5-fluorouracil, were detected in all BCBM. The ratio of BCBM to serum was higher for 5-fluorouracil than for capecitabine. As for lapatinib, the median BCBM concentrations ranged from 1.0 to 6.5 mM. A high variability (0.19-9.8) was noted for lapatinib BCBM-to-serum ratio.
Conclusions. This is the first study to demonstrate that capecitabine and lapatinib penetrate to a significant though variable degree in human BCBM. Drug delivery to BCBM is variable and in many cases appears partially limiting. Elucidating mechanisms that limit drug concentration and innovative approaches to overcome limited drug uptake will be important to improve clinical efficacy of these agents in the central nervous system. Trial registration ID: NCT00795678.
C1 [Morikawa, Aki; Murphy, Conleth G.; Simmons, Ahkeem; Tabar, Viviane; Seidman, Andrew D.] Mem Sloan Kettering Canc Ctr, New York, NY 10065 USA.
[Peereboom, David M.; Weil, Robert J.] Cleveland Clin, Cleveland, OH 44106 USA.
[Thorsheim, Helen R.; Samala, Ramakrishna; Balyan, Rajiv; Lockman, Paul R.; Smith, Quentin R.] Texas Tech Univ, Hlth Sci Ctr, Amarillo, TX USA.
[Steeg, Patricia S.] NCI, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Seidman, AD (reprint author), Mem Sloan Kettering Canc Ctr, Evelyn Lauder Breast Ctr, 300 East 66th St, New York, NY 10065 USA.
EM seidmana@mskcc.org
FU Department of Defense Center of Excellence Breast Cancer Research
Program Award [W81XWH-06-0033]; Judah Gubbay Memorial Fund
FX This work was supported by the Department of Defense Center of
Excellence Breast Cancer Research Program Award (W81XWH-06-0033) and the
Judah Gubbay Memorial Fund.
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U2 11
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 FEB
PY 2015
VL 17
IS 2
BP 289
EP 295
DI 10.1093/neuonc/nou141
PG 7
WC Oncology; Clinical Neurology
SC Oncology; Neurosciences & Neurology
GA CC1XK
UT WOS:000350138500013
PM 25015089
ER
PT J
AU Walton, KM
Abrams, DB
Bailey, WC
Clark, D
Connolly, GN
Djordjevic, MV
Eissenberg, TE
Fiore, MC
Goniewicz, ML
Haverkos, L
Hecht, SS
Henningfield, JE
Hughes, JR
Oncken, CA
Postow, L
Rose, JE
Wanke, KL
Yang, L
Hatsukami, DK
AF Walton, Kevin M.
Abrams, David B.
Bailey, William C.
Clark, David
Connolly, Gregory N.
Djordjevic, Mirjana V.
Eissenberg, Thomas E.
Fiore, Michael C.
Goniewicz, Maciej L.
Haverkos, Lynne
Hecht, Stephen S.
Henningfield, Jack E.
Hughes, John R.
Oncken, Cheryl A.
Postow, Lisa
Rose, Jed E.
Wanke, Kay L.
Yang, Lucie
Hatsukami, Dorothy K.
TI NIH Electronic Cigarette Workshop: Developing a Research Agenda
SO NICOTINE & TOBACCO RESEARCH
LA English
DT Review
ID ABUSE LIABILITY ASSESSMENT; NICOTINE DELIVERY-SYSTEMS; TOBACCO PRODUCTS;
CARBONYL-COMPOUNDS; SMOKING REDUCTION; PREGNANT SMOKERS; UNITED-STATES;
USERS; EXPOSURE; HEALTH
AB Background: Electronic cigarettes (e-cigarettes) represent an emerging public health issue. These devices deliver nicotine along with other constituents, including flavorants, via an inhalable aerosol. Their uptake is rapidly increasing in both adults and youths, primarily among current smokers. Public debate is increasing on how these devices should be regulated and used, yet only limited peer-reviewed research exists. To develop a informed policy for e-cigarettes, their effects on human behavior, physiology, and health need to be understood.
Purpose: This paper describes proceedings from a National Institutes of Health-sponsored workshop, which was held in November 2013, to identify research needs related to the effects of e-cigarettes. Discussion topics included e-cigarette risks and abuse potential; the potential role for e-cigarettes in harm reduction and smoking cessation; unintended consequences of e-cigarette use, such as becoming a gateway to conventional cigarettes; and dual use of both e-cigarettes and conventional cigarettes.
Results and Conclusions: The research needs identified by the workshop participants included the following: standards to measure the contents and emissions of e-cigarettes; biomarkers of exposure; physiological effects of e-cigarettes on tissues and organ systems, including pulmonary and cardiovascular; information on e-cigarette users, how the devices are used, and identification of the best tools to assess these measures; factors that drive use and influence patterns of use; and appropriate methods for evaluating a potential role for e-cigarettes in smoking or nicotine cessation. To understand fully the challenges and the opportunities that e-cigarettes represent, expertise will be needed in basic, behavioral, translational, and clinical sciences.
C1 [Walton, Kevin M.] NIDA, Div Pharmacotherapies & Med Consequences Drug Abu, NIH, Bethesda, MD 20892 USA.
[Abrams, David B.] Schroeder Inst Legacy, Washington, DC USA.
[Abrams, David B.] Johns Hopkins Sch Publ Hlth, Dept Hlth Behav & Soc, Baltimore, MD USA.
[Bailey, William C.] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA.
[Clark, David] Natl Inst Dent & Craniofacial Res, Behav & Social Sci Res Branch, NIH, Bethesda, MD USA.
[Connolly, Gregory N.] Northeastern Univ, Sch Law, Boston, MA 02115 USA.
[Connolly, Gregory N.] Northeastern Univ, Bouve Hlth Sci, Boston, MA 02115 USA.
[Djordjevic, Mirjana V.] NCI, Tobacco Control Res Branch, NIH, Bethesda, MD 20892 USA.
[Eissenberg, Thomas E.] Virginia Commonwealth Univ, Dept Psychol, Richmond, VA 23284 USA.
[Fiore, Michael C.] Univ Wisconsin, Ctr Tobacco Res & Intervent, Madison, WI USA.
[Goniewicz, Maciej L.] Roswell Pk Canc Inst, Dept Hlth Behav, Buffalo, NY 14263 USA.
[Haverkos, Lynne] NICHHD, Child Dev & Behav Branch, NIH, Bethesda, MD 20892 USA.
[Hecht, Stephen S.] Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA.
[Henningfield, Jack E.] Pinney Associates, Bethesda, MD USA.
[Henningfield, Jack E.] Johns Hopkins Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD USA.
[Hughes, John R.] Univ Vermont, Coll Med, Dept Psychol Sci, Burlington, VT USA.
[Oncken, Cheryl A.] Univ Connecticut, Ctr Hlth, Dept Med, Farmington, CT USA.
[Postow, Lisa] NHLBI, Airway Biol & Dis Branch, NIH, Bethesda, MD 20892 USA.
[Rose, Jed E.] Duke Univ, Med Ctr, Ctr Smoking Cessat, Durham, NC USA.
[Wanke, Kay L.] NIH, Off Dis Prevent, Bethesda, MD 20892 USA.
[Yang, Lucie] US FDA, Div Nonprescript Clin Evaluat, Ctr Drug Evaluat & Res, Silver Spring, MD USA.
[Hatsukami, Dorothy K.] Univ Minnesota, Dept Psychiat, Minneapolis, MN 55455 USA.
RP Walton, KM (reprint author), NIDA, Div Pharmacotherapies & Med Consequences Drug Abu, NIH, 6001 Execut Blvd, Bethesda, MD 20892 USA.
EM kevin.walton@nih.gov
OI Hecht, Stephen/0000-0001-7228-1356
FU National Institutes of Health [P50 DA027840]; US Food and Drug
Administration Center for Tobacco Products [U19 CA157345, P50 DA036105]
FX This work was supported by the National Institutes of Health (P50
DA027840 to JER) and by the National Institutes of Health and US Food
and Drug Administration Center for Tobacco Products (U19 CA157345 to DKH
and P50 DA036105 to TEE).
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U1 7
U2 37
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1462-2203
EI 1469-994X
J9 NICOTINE TOB RES
JI Nicotine Tob. Res.
PD FEB
PY 2015
VL 17
IS 2
SI SI
BP 259
EP 269
DI 10.1093/ntr/ntu214
PG 11
WC Substance Abuse; Public, Environmental & Occupational Health
SC Substance Abuse; Public, Environmental & Occupational Health
GA CC1YW
UT WOS:000350142300022
PM 25335949
ER
PT J
AU Buonfrate, D
Sequi, M
Mejia, R
Cimino, RO
Krolewiecki, AJ
Albonico, M
Degani, M
Tais, S
Angheben, A
Requena-Mendez, A
Munoz, J
Nutman, TB
Bisoffi, Z
AF Buonfrate, Dora
Sequi, Marco
Mejia, Rojelio
Cimino, Ruben O.
Krolewiecki, Alejandro J.
Albonico, Marco
Degani, Monica
Tais, Stefano
Angheben, Andrea
Requena-Mendez, Ana
Munoz, Jose
Nutman, Thomas B.
Bisoffi, Zeno
TI Accuracy of Five Serologic Tests for the Follow up of Strongyloides
stercoralis Infection
SO PLOS NEGLECTED TROPICAL DISEASES
LA English
DT Article
ID REAL-TIME PCR; EOSINOPHIL COUNT; DIAGNOSIS; ASSAY; IVERMECTIN;
MANAGEMENT; HOOKWORM; PATTERNS; TOOL
AB Background
Traditional faecal-based methods have poor sensitivity for the detection of S. stercoralis, therefore are inadequate for post-treatment evaluation of infected patients who should be carefully monitored to exclude the persistence of the infection. In a previous study, we demonstrated high accuracy of five serology tests for the screening and diagnosis of strongyloidiasis. Aim of this study is to evaluate the performance of the same five tests for the follow up of patients infected with S. stercoralis.
Methods
Retrospective study on anonymized, cryo-preserved samples available at the Centre for Tropical Diseases (Negrar, Verona, Italy). Samples were collected before and from 3 to 12 months after treatment. The samples were tested with two commercially-available ELISA tests (IVD, Bordier), two techniques based on a recombinant antigen (NIE-ELISA and NIE-LIPS) and one in-house IFAT. The results of each test were evaluated both in relation to the results of fecal examination and to those of a composite reference standard (classifying as positive a sample with positive stools and/or at least three positive serology tests). The associations between the independent variables age and time and the dependent variable value of serological test (for all five tests), were analyzed by linear mixed-effects regression model.
Results
A high proportion of samples demonstrated for each test a seroreversion or a relevant decline (optical density/relative light units halved or decrease of at least two titers for IFAT) at follow up, results confirmed by the linear mixed effects model that showed a trend to seroreversion over time for all tests. In particular, IVD-ELISA (almost 90% samples demonstrated relevant decline) and IFAT (almost 87%) had the best performance. Considering only samples with a complete negativization, NIE-ELISA showed the best performance (72.5% seroreversion).
Conclusions
Serology is useful for the follow up of patients infected with S. stercoralis and determining test of cure.
C1 [Buonfrate, Dora; Albonico, Marco; Degani, Monica; Tais, Stefano; Angheben, Andrea; Bisoffi, Zeno] Sacro Cuore Hosp, CTD, Verona, Italy.
[Buonfrate, Dora; Albonico, Marco; Angheben, Andrea; Requena-Mendez, Ana; Munoz, Jose; Bisoffi, Zeno] Commiss European Communities, Coordinating Resources Assess & Improve Hlth Stat, Hlth Cooperat Work Programme, FP7,GA 261495, Milan, Italy.
[Sequi, Marco] IRCCS Mario Negri Inst Pharmacol Res, Dept Publ Hlth, Milan, Italy.
[Mejia, Rojelio; Nutman, Thomas B.] NIAID, NIH, Bethesda, MD 20892 USA.
[Cimino, Ruben O.; Krolewiecki, Alejandro J.] Univ Nacl Salta, CONICET, Inst Invest Enfermedades Trop, Oran, Argentina.
[Requena-Mendez, Ana; Munoz, Jose] Univ Barcelona, Hosp Clin, Barcelona Ctr Int Hlth Res CRESIB, Barcelona, Spain.
RP Buonfrate, D (reprint author), Sacro Cuore Hosp, CTD, Verona, Italy.
EM dora.buonfrate@sacrocuore.it
OI Munoz Gutierrez, Jose/0000-0002-0945-1735; ALBONICO,
Marco/0000-0002-7805-2391
FU EC within the 7th Framework Programme under the COHEMI project
[FP7-GA-261495]; Division of Intramural Research of the National
Institute of Allergy and Infectious Diseases (NIAID)
FX This work has been partly supported by the EC within the 7th Framework
Programme under the COHEMI project - grant agreement n. FP7-GA-261495.
The work performed by RM, ROC, and TBN was funded in part by the
Division of Intramural Research of the National Institute of Allergy and
Infectious Diseases (NIAID). We thank Bordier Affinity Products SA for
donating the Bordier ELISA kits. The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 31
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U1 7
U2 8
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1935-2735
J9 PLOS NEGLECT TROP D
JI Plos Neglect. Trop. Dis.
PD FEB
PY 2015
VL 9
IS 2
AR UNSP e0003491
DI 10.1371/journal.pntd.0003491
PG 12
WC Infectious Diseases; Parasitology; Tropical Medicine
SC Infectious Diseases; Parasitology; Tropical Medicine
GA CD3PW
UT WOS:000350992500035
PM 25668740
ER
PT J
AU Mondragon-Shem, K
Al-Salem, WS
Kelly-Hope, L
Abdeladhim, M
Al-Zahrani, MH
Valenzuela, JG
Acosta-Serrano, A
AF Mondragon-Shem, Karina
Al-Salem, Waleed S.
Kelly-Hope, Louise
Abdeladhim, Maha
Al-Zahrani, Mohammed H.
Valenzuela, Jesus G.
Acosta-Serrano, Alvaro
TI Severity of Old World Cutaneous Leishmaniasis Is Influenced by Previous
Exposure to Sandfly Bites in Saudi Arabia
SO PLOS NEGLECTED TROPICAL DISEASES
LA English
DT Article
ID CANINE ANTIBODY-RESPONSE; PHLEBOTOMUS-PAPATASI; VISCERAL LEISHMANIASIS;
IMMUNE-RESPONSE; LUTZOMYIA-LONGIPALPIS; SALIVARY ANTIGEN; MICE BITTEN;
FLY SALIVA; VECTOR; INFECTION
AB Background
The sandfly Phlebotomus papatasi is the vector of Leishmania major, the main causative agent of Old World cutaneous leishmaniasis (CL) in Saudi Arabia. Sandflies inject saliva while feeding and the salivary protein PpSP32 was previously shown to be a biomarker for bite exposure. Here we used recombinant PpSP32 to evaluate human exposure to Ph. papatasi bites, and study the association between antibody response to saliva and CL in endemic areas in Saudi Arabia.
Methodology/Principal Findings
In this observational study, anti-PpSP32 antibodies, as indicators of exposure to sandfly bites, were measured in sera from healthy individuals and patients from endemic regions in Saudi Arabia with active and cured CL. Ph. papatasi was identified as the primary CL vector in the study area. Anti-PpSP32 antibody levels were significantly higher in CL patients presenting active infections from all geographical regions compared to CL cured and healthy individuals. Furthermore, higher anti-PpSP32 antibody levels correlated with the prevalence and type of CL lesions (nodular vs. papular) observed in patients, especially non-local construction workers.
Conclusions
Our findings suggest a possible correlation between the type of immunity generated by the exposure to sandfly bites and disease outcome.
C1 [Mondragon-Shem, Karina; Al-Salem, Waleed S.; Kelly-Hope, Louise; Acosta-Serrano, Alvaro] Univ Liverpool, Liverpool Sch Trop Med, Dept Parasitol, Liverpool L3 5QA, Merseyside, England.
[Al-Salem, Waleed S.; Al-Zahrani, Mohammed H.] Saudi Minist Hlth, Dept Vector Borne Dis, Riyadh, Saudi Arabia.
[Kelly-Hope, Louise] Univ Liverpool, Liverpool Sch Trop Med, Ctr Neglected Trop Dis, Liverpool L3 5QA, Merseyside, England.
[Abdeladhim, Maha; Valenzuela, Jesus G.] NIAID, Vector Mol Biol Sect, NIH, Bethesda, MD 20892 USA.
[Acosta-Serrano, Alvaro] Univ Liverpool, Liverpool Sch Trop Med, Dept Vector Biol, Liverpool L3 5QA, Merseyside, England.
RP Mondragon-Shem, K (reprint author), Univ Liverpool, Liverpool Sch Trop Med, Dept Parasitol, Liverpool L3 5QA, Merseyside, England.
EM alvaro.acosta-serrano@lstmed.ac.uk
RI Acosta-Serrano, Alvaro/L-5503-2015;
OI Acosta-Serrano, Alvaro/0000-0002-2576-7959; Mondragon-Shem,
Karina/0000-0002-0997-5600
FU Ministry of Health of the Kingdom of Saudi Arabia; Colombian Department
of Science, Technology and Innovation (Colciencias) through the
scholarship programme "Francisco Jose de Caldas"; Intramural Research
Program of the National Institutes of Health, National Institute of
Allergy and Infectious Diseases
FX This work was supported in part by a Ph.D. studentship from the Ministry
of Health of the Kingdom of Saudi Arabia (to WSAS); by the Colombian
Department of Science, Technology and Innovation (Colciencias) through
the scholarship programme "Francisco Jose de Caldas" (to KMS); and in
part by the Intramural Research Program of the National Institutes of
Health, National Institute of Allergy and Infectious Diseases (to MA and
JGV). The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 40
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Z9 8
U1 1
U2 11
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1935-2735
J9 PLOS NEGLECT TROP D
JI Plos Neglect. Trop. Dis.
PD FEB
PY 2015
VL 9
IS 2
AR e0003449
DI 10.1371/journal.pntd.0003449
PG 14
WC Infectious Diseases; Parasitology; Tropical Medicine
SC Infectious Diseases; Parasitology; Tropical Medicine
GA CD3PW
UT WOS:000350992500016
PM 25646796
ER
PT J
AU Nutting, CS
Eversole, RR
Blair, K
Specht, S
Nutman, TB
Klion, AD
Wanji, S
Boussinesq, M
Mackenzie, CD
AF Nutting, Chuck S.
Eversole, Rob R.
Blair, Kevin
Specht, Sabine
Nutman, Thomas B.
Klion, Amy D.
Wanji, Samuel
Boussinesq, Michel
Mackenzie, Charles D.
TI Analysis of Nematode Motion Using an Improved Light-Scatter Based System
SO PLOS NEGLECTED TROPICAL DISEASES
LA English
DT Article
ID DRUGS; ONCHOCERCIASIS; ELIMINATION; INFECTION; MOTILITY; FILARIAE
AB Background
The detailed assessment of nematode activity and viability still remains a relatively undeveloped area of biological and medical research. Computer-based approaches to assessing the motility of larger nematode stages have been developed, yet these lack the capability to detect and analyze the more subtle and important characteristics of the motion of nematodes. There is currently a need to improved methods of assessing the viability and health of parasitic worms.
Methods
We describe here a system that converts the motion of nematodes through a light-scattering system into an electrical waveform, and allows for reproducible, and wholly non-subjective, assessment of alterations in motion, as well as estimation of the number of nematode worms of different forms and sizes. Here we have used Brugia sp. microfilariae (L1), infective larvae (L3) and adults, together with the free-living nematode Caenorhabditis elegans.
Results
The motion of worms in a small (200ul) volume can be detected, with the presence of immotile worms not interfering with the readings at practical levels (up to at least 500 L1 /200ul). Alterations in the frequency of parasite movement following the application of the anti-parasitic drugs, (chloroquine and imatinib); the anti-filarial effect of the latter agent is the first demonstrated here for the first time. This system can also be used to estimate the number of parasites, and shortens the time required to estimate parasites numbers, and eliminates the need for microscopes and trained technicians to provide an estimate of microfilarial sample sizes up to 1000 parasites/ml. Alterations in the form of motion of the worms can also be depicted.
Conclusions
This new instrument, named a "WiggleTron", offers exciting opportunities to further study nematode biology and to aid drug discovery, as well as contributing to a rapid estimate of parasite numbers in various biological samples.
C1 [Nutting, Chuck S.; Eversole, Rob R.; Blair, Kevin; Mackenzie, Charles D.] Western Michigan Univ, Dept Biol Sci, Kalamazoo, MI 49008 USA.
[Blair, Kevin] Western Michigan Univ, Dept Chem, Kalamazoo, MI 49008 USA.
[Specht, Sabine] Univ Hosp Bonn, Inst Med Microbiol, Bonn, Germany.
[Nutman, Thomas B.; Klion, Amy D.] NIH, Parasit Dis Lab, Bethesda, MD 20892 USA.
[Wanji, Samuel] Inst Rech Dev, Montpellier, France.
[Boussinesq, Michel] Univ Buea, Res Fdn Trop Dis & Environm, Buea, Cameroon.
[Mackenzie, Charles D.] Michigan State Univ, Dept Pathobiol & Diagnost Invest, E Lansing, MI 48824 USA.
RP Nutting, CS (reprint author), Western Michigan Univ, Dept Biol Sci, Kalamazoo, MI 49008 USA.
EM mackenz8@msu.edu
RI Boussinesq, Michel/J-7256-2016;
OI Boussinesq, Michel/0000-0001-6312-0681; Klion, Amy/0000-0002-4986-5326
FU Bill and Melinda Gates Foundation
FX This work was supported The Bill and Melinda Gates Foundation. The
funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 21
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U1 0
U2 6
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1935-2735
J9 PLOS NEGLECT TROP D
JI Plos Neglect. Trop. Dis.
PD FEB
PY 2015
VL 9
IS 2
AR e0003523
DI 10.1371/journal.pntd.0003523
PG 15
WC Infectious Diseases; Parasitology; Tropical Medicine
SC Infectious Diseases; Parasitology; Tropical Medicine
GA CD3PW
UT WOS:000350992500049
PM 25695776
ER
PT J
AU Blackshear, PE
Pandiri, AR
Nagai, H
Bhusari, S
Hong, HH
Ton, TVT
Clayton, NP
Wyde, M
Shockley, KR
Peddada, SD
Gerrish, KE
Sills, RC
Hoenerhoff, MJ
AF Blackshear, Pamela E.
Pandiri, Arun R.
Nagai, Hiroaki
Bhusari, Sachin
Hong, Hue-Hua
Ton, Thai-Vu T.
Clayton, Natasha P.
Wyde, Michael
Shockley, Keith R.
Peddada, Shyamal D.
Gerrish, Kevin E.
Sills, Robert C.
Hoenerhoff, Mark J.
TI Gene Expression of Mesothelioma in Vinylidene Chloride-exposed F344/N
Rats Reveal Immune Dysfunction, Tissue Damage, and Inflammation Pathways
SO TOXICOLOGIC PATHOLOGY
LA English
DT Article
DE vinylidene chloride; mesothelioma; F344; N rat; National Toxicology
Program; microarray; gene expression; mesothelial cell; Fred-PE cells
ID MALIGNANT PLEURAL MESOTHELIOMA; NATURAL-KILLER-CELLS; PULMONARY
ADENOCARCINOMA; SIGNAL-TRANSDUCTION; MOLECULAR PATHWAYS; TUNICA
VAGINALIS; GAMMA-SYNUCLEIN; PROBE LEVEL; IN-VIVO; CANCER
AB A majority (approximate to 80%) of human malignant mesotheliomas are asbestos-related. However, non-asbestos risk factors (radiation, chemicals, and genetic factors) account for up to 30% of cases. A recent 2-year National Toxicology Program carcinogenicity bioassay showed that male F344/N rats exposed to the industrial toxicant vinylidene chloride (VDC) resulted in a marked increase in malignant mesothelioma. Global gene expression profiles of these tumors were compared to spontaneous mesotheliomas and the F344/N rat mesothelial cell line (Fred-PE) in order to characterize the molecular features and chemical-specific profiles of mesothelioma in VDC-exposed rats. As expected, mesotheliomas from control and VDC-exposed rats shared pathways associated with tumorigenesis, including cellular and tissue development, organismal injury, embryonic development, inflammatory response, cell cycle regulation, and cellular growth and proliferation, while mesotheliomas from VDC-exposed rats alone showed overrepresentation of pathways associated with pro-inflammatory pathways and immune dysfunction such as the nuclear factor kappa-light-chain-enhancer of activated B cells signaling pathway, interleukin (IL)-8 and IL-12 signaling, interleukin responses, Fc receptor signaling, and natural killer and dendritic cells signaling, as well as overrepresentation of DNA damage and repair. These data suggest that a chronic, pro-inflammatory environment associated with VDC exposure may exacerbate disturbances in oncogene, growth factor, and cell cycle regulation, resulting in an increased incidence of mesothelioma.
C1 [Blackshear, Pamela E.; Pandiri, Arun R.; Nagai, Hiroaki; Bhusari, Sachin; Hong, Hue-Hua; Ton, Thai-Vu T.; Clayton, Natasha P.; Sills, Robert C.; Hoenerhoff, Mark J.] NIEHS, Cellular & Mol Pathol Branch, Res Triangle Pk, NC 27709 USA.
[Blackshear, Pamela E.] Integrated Syst Lab Inc, Res Triangle Pk, NC USA.
[Pandiri, Arun R.] Expt Pathol Labs Inc, Res Triangle Pk, NC USA.
[Wyde, Michael] NIEHS, Expt Toxicol Grp, Div Natl Toxicol Program, Res Triangle Pk, NC 27709 USA.
[Shockley, Keith R.; Peddada, Shyamal D.] NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA.
[Gerrish, Kevin E.] NIEHS, Lab Toxicol & Pharmacol, Res Triangle Pk, NC 27709 USA.
RP Hoenerhoff, MJ (reprint author), Univ Michigan, Sch Med, Unit Lab Anim Med, North Campus Res Complex,2800 Plymouth Rd, Ann Arbor, MI 48103 USA.
EM hoenerho@med.umich.edu
FU Intramural NIH HHS [Z99 ES999999]
NR 62
TC 1
Z9 1
U1 0
U2 3
PU SAGE PUBLICATIONS INC
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 FEB
PY 2015
VL 43
IS 2
BP 171
EP 185
DI 10.1177/0192623314537885
PG 15
WC Pathology; Toxicology
SC Pathology; Toxicology
GA CC4RO
UT WOS:000350341100002
PM 24958746
ER
PT J
AU Kaess, BM
Harris, WS
Lacey, S
Larson, MG
Hamburg, NM
Vita, JA
Robins, SJ
Benjamin, EJ
Mitchell, GF
Vasan, RS
AF Kaess, Bernhard M.
Harris, William S.
Lacey, Sean
Larson, Martin G.
Hamburg, Naomi M.
Vita, Joseph A.
Robins, Sander J.
Benjamin, Emelia J.
Mitchell, Gary F.
Vasan, Ramachandran S.
TI The relation of red blood cell fatty acids with vascular stiffness,
cardiac structure and left ventricular function: The Framingham Heart
Study
SO VASCULAR MEDICINE
LA English
DT Article
DE aortic stiffness; fatty acids
ID LONG-CHAIN OMEGA-3-FATTY-ACIDS; INTIMA-MEDIA THICKNESS; GISSI-HF TRIAL;
CARDIOVASCULAR-DISEASE; ARTERIAL STIFFNESS; EICOSAPENTAENOIC ACID; FISH
CONSUMPTION; DOCOSAHEXAENOIC ACID; SECONDARY PREVENTION; AORTIC
STIFFNESS
AB Polyunsaturated fatty acids have been associated with beneficial influences on cardiovascular health. However, the underlying mechanisms are not clear, and data on the relations of polyunsaturated fatty acids to subclinical disease measures such as vascular stiffness and cardiac function are sparse and inconclusive. In a large community-based cohort, we examined the relations of omega-3 and other fatty acids to a comprehensive panel of vascular function measures (assessing microvascular function and large artery stiffness), cardiac structure and left ventricular function. Red blood cell (RBC) membrane fatty acid composition, a measure of long-term fatty acid intake, was assessed in participants of the Framingham Offspring Study and Omni cohorts and related to tonometry-derived measures of vascular stiffness and to a panel of echocardiographic traits using partial correlations. Up to n=3055 individuals (56% women, mean age 66 years) were available for analyses. In age- and sex-adjusted models, higher RBC omega-3 content was moderately associated (p0.002) with several measures of vascular stiffness and function in a protective direction. However, after multivariable adjustment, only an association of higher RBC omega-3 content with lower carotid-femoral pulse wave velocity (a measure of aortic stiffness) remained significant (r = -0.06, p=0.002). In secondary analyses, higher linoleic acid, the major nutritional omega-6 fatty acid, was associated with smaller left atrial size, even after multivariable adjustment (r = -0.064, p<0.001). In conclusion, in our cross-sectional community-based study, we found several associations consistent with the notion of protective effects of omega-3 and linoleic acid. The clinical significance of these modest associations remains to be elucidated.
C1 [Kaess, Bernhard M.; Larson, Martin G.; Robins, Sander J.; Benjamin, Emelia J.; Vasan, Ramachandran S.] NHLBI, Framingham, MA USA.
[Kaess, Bernhard M.; Larson, Martin G.; Robins, Sander J.; Benjamin, Emelia J.; Vasan, Ramachandran S.] Boston Univ, Framingham Heart Study, Framingham, MA USA.
[Kaess, Bernhard M.] Tech Univ Munich, Deutsch Herzzentrum, D-80290 Munich, Germany.
[Harris, William S.] Univ S Dakota, Sanford Sch Med, Dept Med, Sioux Falls, SD USA.
[Harris, William S.] Hlth Diagnost Lab Inc, Richmond, VA USA.
[Lacey, Sean; Larson, Martin G.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Larson, Martin G.; Benjamin, Emelia J.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA.
[Hamburg, Naomi M.; Vita, Joseph A.; Benjamin, Emelia J.; Vasan, Ramachandran S.] Boston Univ, Sch Med, Evans Dept Med, Boston, MA 02118 USA.
[Hamburg, Naomi M.; Vita, Joseph A.; Benjamin, Emelia J.; Vasan, Ramachandran S.] Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Boston, MA 02118 USA.
[Benjamin, Emelia J.; Vasan, Ramachandran S.] Boston Univ, Sch Med, Dept Med, Sect Prevent Med, Boston, MA 02118 USA.
[Benjamin, Emelia J.; Vasan, Ramachandran S.] Boston Univ, Sch Med, Dept Med, Cardiol Sect, Boston, MA 02118 USA.
[Mitchell, Gary F.] Cardiovasc Engn Inc, Norwood, MA USA.
RP Kaess, BM (reprint author), Deutsch Herzzentrum Munich, Lazarettstr 36, D-80636 Munich, Germany.
EM bernhard_kaess@gmx.de
OI Benjamin, Emelia/0000-0003-4076-2336; Ramachandran,
Vasan/0000-0001-7357-5970
FU National Heart, Lung, and Blood Institute (NHLBI) [R01 HL089590];
Framingham Heart Study (NHLBI) [N01-HC-25195]; Boston University School
of Medicine; [HL076784]; [G028321]; [HL070100]; [HL060040];
[HL080124]; [HL071039]; [HL077447]; [HL107385]; [2-K24-HL04334]
FX This work was supported by the National Heart, Lung, and Blood Institute
(NHLBI; R01 HL089590) and by contract N01-HC-25195, the Framingham Heart
Study (NHLBI) and Boston University School of Medicine, and by HL076784,
G028321, HL070100, HL060040, HL080124, HL071039, HL077447, HL107385, and
2-K24-HL04334.
NR 54
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Z9 4
U1 0
U2 9
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 1358-863X
EI 1477-0377
J9 VASC MED
JI Vasc. Med.
PD FEB
PY 2015
VL 20
IS 1
BP 5
EP 13
DI 10.1177/1358863X14560808
PG 9
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA CC6JY
UT WOS:000350472400002
PM 25520318
ER
PT J
AU Massimelli, MJ
Majerciak, V
Kang, JG
Liewehr, DJ
Steinberg, SM
Zheng, ZM
AF Massimelli, Maria Julia
Majerciak, Vladimir
Kang, Jeong-Gu
Liewehr, David J.
Steinberg, Seth M.
Zheng, Zhi-Ming
TI Multiple Regions of Kaposi's Sarcoma-Associated Herpesvirus ORF59 RNA
are Required for Its Expression Mediated by Viral ORF57 and Cellular
RBM15
SO VIRUSES-BASEL
LA English
DT Article
ID PROCESSIVITY FACTOR ORF59; PROTEIN INTERACTS; GENE-EXPRESSION;
DNA-REPLICATION; ELEMENT; RTA; TRANSACTIVATOR; POLYMERASE; REGULATOR;
INFECTION
AB KSHV ORF57 (MTA) promotes RNA stability of ORF59, a viral DNA polymerase processivity factor. Here, we show that the integrity of both ORF59 RNA ends is necessary for ORF57-mediated ORF59 expression and deletion of both 5' and 3' regions, or one end region with a central region, of ORF59 RNA prevents ORF57-mediated translation of ORF59. The ORF59 sequence between nt 96633 and 96559 resembles other known MTA-responsive elements (MREs). ORF57 specifically binds to a stem-loop region from nt 96596-96572 of the MRE, which also binds cellular RBM15. Internal deletion of the MRE from ORF59 led to poor export, but accumulation of nuclear ORF59 RNA in the presence of ORF57 or RBM15. Despite of being translatable in the presence of ORF57, this deletion mutant exhibits translational defect in the presence of RBM15. Together, our results provide novel insight into the roles of ORF57 and RBM15 in ORF59 RNA accumulation and protein translation.
C1 [Massimelli, Maria Julia; Majerciak, Vladimir; Kang, Jeong-Gu; Zheng, Zhi-Ming] NCI, Tumor Virus RNA Biol Sect, Gene Regulat & Chromosome Biol Lab, Ctr Canc Res,NIH, Frederick, MD 21702 USA.
[Liewehr, David J.; Steinberg, Seth M.] NCI, Biostat & Data Management Sect, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Zheng, ZM (reprint author), NCI, Tumor Virus RNA Biol Sect, Gene Regulat & Chromosome Biol Lab, Ctr Canc Res,NIH, 1050 Boyles St, Frederick, MD 21702 USA.
EM julia.massimelli@uci.edu; majerciv@mail.nih.gov; jkang@jkbiopharma.com;
liewehrd@mail.nih.gov; steinbes@mail.nih.gov; zhengt@exchange.nih.gov
FU Intramural Research Program of the National Cancer Institute, Center for
Cancer Research, NIH
FX This work was supported by the Intramural Research Program of the
National Cancer Institute, Center for Cancer Research, NIH. We thank
Barbara Felber at NCI for RBM15 plasmid and Jae Jung of the University
of Southern California for inducible TREx BCBL1-RTA and -vector cell
lines.
NR 30
TC 4
Z9 4
U1 0
U2 0
PU MDPI AG
PI BASEL
PA POSTFACH, CH-4005 BASEL, SWITZERLAND
SN 1999-4915
J9 VIRUSES-BASEL
JI Viruses-Basel
PD FEB
PY 2015
VL 7
IS 2
BP 496
EP 510
DI 10.3390/v7020496
PG 15
WC Virology
SC Virology
GA CC9EL
UT WOS:000350670800003
PM 25690794
ER
PT J
AU Judson, S
Prescott, J
Munster, V
AF Judson, Seth
Prescott, Joseph
Munster, Vincent
TI Understanding Ebola Virus Transmission
SO VIRUSES-BASEL
LA English
DT Review
ID HEMORRHAGIC-FEVER; RHESUS-MONKEYS; RISK-FACTORS; INFECTION; EXPOSURE;
AEROSOL; ZAIRE; PATHOLOGY; SURVIVAL; KIKWIT
AB An unprecedented number of Ebola virus infections among healthcare workers and patients have raised questions about our understanding of Ebola virus transmission. Here, we explore different routes of Ebola virus transmission between people, summarizing the known epidemiological and experimental data. From this data, we expose important gaps in Ebola virus research pertinent to outbreak situations. We further propose experiments and methods of data collection that will enable scientists to fill these voids in our knowledge about the transmission of Ebola virus.
C1 [Judson, Seth; Prescott, Joseph; Munster, Vincent] NIAID, Virol Lab, Div Intramural Res, NIH, Hamilton, MT 59840 USA.
RP Munster, V (reprint author), NIAID, Virol Lab, Div Intramural Res, NIH, Hamilton, MT 59840 USA.
EM sethdjudson@gmail.com; prescottjb@niaid.nih.gov; munstervj@niaid.nih.gov
OI Munster, Vincent/0000-0002-2288-3196
FU Intramural Research Program of the National Institute of Allergy and
Infectious Diseases, National Institutes of Health
FX We would like to thank Austin Athman, Ryan Kissinger and Anita Mora
(RTB, DIR, NIAID, NIH) for help creating the Figure. This work was
supported by the Intramural Research Program of the National Institute
of Allergy and Infectious Diseases, National Institutes of Health.
NR 24
TC 17
Z9 17
U1 2
U2 40
PU MDPI AG
PI BASEL
PA POSTFACH, CH-4005 BASEL, SWITZERLAND
SN 1999-4915
J9 VIRUSES-BASEL
JI Viruses-Basel
PD FEB
PY 2015
VL 7
IS 2
BP 511
EP 521
DI 10.3390/v7020511
PG 11
WC Virology
SC Virology
GA CC9EL
UT WOS:000350670800004
PM 25654239
ER
PT J
AU Majerciak, V
Zheng, ZM
AF Majerciak, Vladimir
Zheng, Zhi-Ming
TI KSHV ORF57, a Protein of Many Faces
SO VIRUSES-BASEL
LA English
DT Review
ID SARCOMA-ASSOCIATED HERPESVIRUS; MESSENGER-RNA EXPORT; SIMPLEX-VIRUS
ICP27; POLYADENYLATED NUCLEAR-RNA; KINASE CK2 PHOSPHORYLATION; LYTIC
GENE-EXPRESSION; EXON-JUNCTION COMPLEX; ARGININE-RICH MOTIFS; LONG
NONCODING RNA; REGULATORY PROTEIN
AB Kaposi's sarcoma-associated herpesvirus (KSHV) ORF57 protein (also known as mRNA transcript accumulation (Mta)) is a potent posttranscriptional regulator essential for the efficient expression of KSHV lytic genes and productive KSHV replication. ORF57 possesses numerous activities that promote the expression of viral genes, including the three major functions of enhancement of RNA stability, promotion of RNA splicing, and stimulation of protein translation. The multifunctional nature of ORF57 is driven by its ability to interact with an array of cellular cofactors. These interactions are required for the formation of ORF57-containing ribonucleoprotein complexes at specific binding sites in the target transcripts, referred as Mta-responsive elements (MREs). Understanding of the ORF57 protein conformation has led to the identification of two structurally-distinct domains within the ORF57 polypeptide: an unstructured intrinsically disordered N-terminal domain and a structured alpha-helix-rich C-terminal domain. The distinct structures of the domains serve as the foundation for their unique binding affinities: the N-terminal domain mediates ORF57 interactions with cellular cofactors and target RNAs, and the C-terminal domain mediates ORF57 homodimerization. In addition, each domain has been found to contribute to the stability of ORF57 protein in infected cells by counteracting caspase- and proteasome-mediated degradation pathways. Together, these new findings provide insight into the function and biological properties of ORF57 in the KSHV life cycle and pathogenesis.
C1 [Majerciak, Vladimir; Zheng, Zhi-Ming] NCI, Tumor Virus RNA Biol Sect, Gene Regulat & Chromosome Biol Lab, NIH, Frederick, MD 21702 USA.
RP Zheng, ZM (reprint author), NCI, Tumor Virus RNA Biol Sect, Gene Regulat & Chromosome Biol Lab, NIH, 1050 Boyles St, Frederick, MD 21702 USA.
EM Vladimir.Majerciak@nih.gov; zhengt@exchange.nih.gov
FU National Cancer Institute, Center for Cancer Research, NIH
FX This work was supported by the Intramural Research Program of the
National Cancer Institute, Center for Cancer Research, NIH.
NR 119
TC 4
Z9 4
U1 2
U2 6
PU MDPI AG
PI BASEL
PA POSTFACH, CH-4005 BASEL, SWITZERLAND
SN 1999-4915
J9 VIRUSES-BASEL
JI Viruses-Basel
PD FEB
PY 2015
VL 7
IS 2
BP 604
EP 633
DI 10.3390/v7020604
PG 30
WC Virology
SC Virology
GA CC9EL
UT WOS:000350670800009
PM 25674768
ER
PT J
AU Sun, XL
Cai, WB
Chen, XY
AF Sun, Xiaolian
Cai, Weibo
Chen, Xiaoyuan
TI Positron Emission Tomography Imaging Using Radio labeled Inorganic
Nanomaterials
SO ACCOUNTS OF CHEMICAL RESEARCH
LA English
DT Review
ID IRON-OXIDE NANOPARTICLES; IN-VIVO; THERANOSTIC NANOPARTICLES; TUMOR
VASCULATURE; CARBON NANOTUBES; QUANTUM DOTS; CANCER; PET; THERAPY;
RADIOPHARMACEUTICALS
AB Positron emission tomography (PET) is a radionuclide imaging technology that plays an important role in preclinical and clinical research. With administration of a small amount of radiotracer, PET imaging can provide a noninvasive, highly sensitive, and quantitative readout of its organ/tissue targeting efficiency and pharmacokinetics. Various radiotracers have been designed to target specific molecular events. Compared with antibodies, proteins, peptides, and other biologically relevant molecules, nanoparticles represent a new frontier in molecular imaging probe design, enabling the attachment of different imaging modalities, targeting ligands, and therapeutic payloads in a single vector.
We introduce the radiolabeled nanoparticle platforms that we and others have developed. Due to the fundamental differences in the various nanoparticles and radioisotopes, most radiolabeling methods are designed case-by-case. We focus on some general rules about selecting appropriate isotopes for given types of nanoparticles, as well as adjusting the labeling strategies according to specific applications. We classified these radiolabeling methods into four categories: (1) complexation reaction of radiometal ions with chelators via coordination chemistry; (2) direct bombardment of nanoparticles via hadronic projectiles; (3) synthesis of nanoparticles using a mixture of radioactive and nonradioactive precursors; (4) chelator-free postsynthetic radiolabeling. Method 1 is generally applicable to different nanomaterials as long as the surface chemistry is well-designed. However, the addition of chelators brings concerns of possible changes to the physicochemical properties of nanomaterials and detachment of the radiometal. Methods 2 and 3 have improved radiochemical stability. The applications are, however, limited by the possible damage to the nanocomponent caused by the proton beams (method 2) and harsh synthetic conditions (method 3). Method 4 is still in its infancy. Although being fast and specific, only a few combinations of isotopes and nanoparticles have been explored. Since the applications of radiolabeled nanoparticles are based on the premise that the radioisotopes are stably attached to the nanomaterials, stability (colloidal and radiochemical) assessment of radiolabeled nanoparticles is also highlighted.
Despite the fact that thousands of nanomaterials have been developed for clinical research, only very few have moved to humans. One major reason is the lack of understanding of the biological behavior of nanomaterials. We discuss specific examples of using PET imaging to monitor the in vivo fate of radiolabeled nanoparticles, emphasizing the importance of labeling strategies and caution in interpreting PET data. Design considerations for radiolabeled nanoplatforms for multimodal molecular imaging are also illustrated, with a focus on strategies to combine the strengths of different imaging modalities and to prolong the circulation time.
C1 [Sun, Xiaolian] Xiamen Univ, Sch Publ Hlth, State Key Lab Mol Vaccinol & Mol Diagnost, Ctr Mol Imaging & Translat Med, Xiamen 361102, Peoples R China.
[Sun, Xiaolian; Chen, Xiaoyuan] Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA.
[Cai, Weibo] Univ Wisconsin, Dept Radiol, Madison, WI 53706 USA.
[Cai, Weibo] Univ Wisconsin, Dept Phys Med, Madison, WI 53706 USA.
RP Sun, XL (reprint author), Xiamen Univ, Sch Publ Hlth, State Key Lab Mol Vaccinol & Mol Diagnost, Ctr Mol Imaging & Translat Med, Xiangan South Rd, Xiamen 361102, Peoples R China.
EM xiaolian.sun@nih.gov; WCai@uwhealth.org; shawn.chen@nih.gov
FU intramural research program of the National Institute of Biomedical
Imaging and Bioengineering (NIBIB); University of Wisconsin-Madison;
National Institutes of Health [NIBIB/NCI 1R01CA169365]; Department of
Defense [W81XWH-11-1-0644]; American Cancer Society
[125246-RSG-13-099-01-CCE]
FX We thank the intramural research program of the National Institute of
Biomedical Imaging and Bioengineering (NIBIB), the University of
Wisconsin-Madison, the National Institutes of Health (Grant NIBIB/NCI
1R01CA169365), the Department of Defense (Grant W81XWH-11-1-0644), and
the American Cancer Society (Grant 125246-RSG-13-099-01-CCE) for the
support of this work.
NR 56
TC 37
Z9 37
U1 17
U2 93
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0001-4842
EI 1520-4898
J9 ACCOUNTS CHEM RES
JI Accounts Chem. Res.
PD FEB
PY 2015
VL 48
IS 2
BP 286
EP 294
DI 10.1021/ar500362y
PG 9
WC Chemistry, Multidisciplinary
SC Chemistry
GA CB7KS
UT WOS:000349806300016
PM 25635467
ER
PT J
AU Breslow, RA
Dong, CH
White, A
AF Breslow, Rosalind A.
Dong, Chuanhui
White, Aaron
TI Prevalence of Alcohol-Interactive Prescription Medication Use Among
Current Drinkers: United States, 1999 to 2010
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Article
DE Alcohol Consumption; Drinking Patterns; Drinking Behavior; Drugs;
Medications; Prescription Medications; Cross-Sectional Survey; National
Health and Nutrition Examination Survey
AB BackgroundThe majority of Americans consume alcoholic beverages. Alcohol interacts negatively with numerous commonly prescribed medications. Yet, on a population level, little is known about use of alcohol-interactive (AI) prescription medications among drinkers. The purpose of our study was to determine the prevalence of AI prescription medication use among current drinkers in the U.S. population.
MethodsData were from the National Health and Nutrition Examination Survey (NHANES 1999 to 2010); 26,657 adults aged 20years had data on past year alcohol consumption and past month prescription medication use. Analyses were adjusted for covariates: age, race/ethnicity, education, marital status, and smoking. Statistical procedures accounted for survey stratification, clustering, and nonresponse. Analyses were weighted to be nationally representative.
ResultsThe unadjusted total prevalence of AI medication use was 42.8% (95% confidence interval [CI] 41.5 to 44.0). Among current drinkers, adjusted prevalence was 41.5% (CI 40.3 to 42.7). Among participants aged 65 total prevalence of AI medication use was 78.6% (CI 77.3 to 79.9) and adjusted prevalence among current drinkers was 77.8% (CI 75.7 to 79.7). The AI medications most commonly used by current drinkers were cardiovascular agents, central nervous system agents, and metabolic agents.
ConclusionsOur results suggest that there could be substantial simultaneous exposure to alcohol and AI prescription medications in the U.S. population. Given the adverse health risks of combining alcohol with AI prescription medications, future efforts are needed to collect data to determine actual simultaneous prevalence.
C1 [Breslow, Rosalind A.; White, Aaron] NIAAA, Div Epidemiol & Prevent Res, NIH, Rockville, MD 20892 USA.
[Dong, Chuanhui] CSR Inc, Arlington, VA USA.
RP Breslow, RA (reprint author), NIAAA, Div Epidemiol & Prevent Res, 5635 Fishers Lane,Room 2071, Rockville, MD 20892 USA.
EM rbreslow@mail.nih.gov
FU Intramural NIH HHS [Z99 AA999999]
NR 22
TC 9
Z9 9
U1 1
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0145-6008
EI 1530-0277
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD FEB
PY 2015
VL 39
IS 2
BP 371
EP 379
DI 10.1111/acer.12633
PG 9
WC Substance Abuse
SC Substance Abuse
GA CC1KZ
UT WOS:000350100900020
PM 25597432
ER
PT J
AU Ahrens, KA
Cole, SR
Westreich, D
Platt, RW
Schisterman, EF
AF Ahrens, K. A.
Cole, S. R.
Westreich, D.
Platt, R. W.
Schisterman, E. F.
TI A Cautionary Note About Estimating Effects of Secondary Exposures in
Cohort Studies
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE bias (epidemiology); cohort studies; directed acyclic graph;
epidemiologic methods; oversampling
ID CAUSAL DIAGRAMS; MODELS; EPIDEMIOLOGY; ADJUSTMENT; BIAS
AB Cohort studies are often enriched for a primary exposure of interest to improve cost-effectiveness, which presents analytical challenges not commonly discussed in epidemiology. In this paper, we use causal diagrams to represent exposure-enriched cohort studies, illustrate a scenario wherein the risk ratio for the effect of a secondary exposure on an outcome is biased, and propose an analytical method for correcting for such bias. In our motivating example, maternal smoking (Z) is a cause of fetal growth restriction (X), which subsequently affects preterm birth (Y) (i.e., Z -> X -> Y); strong positive associations exist between both Z, X and X, Y; and enrichment for X increases its prevalence from 10% to 50%. In the X-enriched cohort, unadjusted and X-adjusted analyses lead to bias in the risk ratio for the total effect of Z on Y. After application of inverse probability weights, the bias is corrected, with a small loss of efficiency in comparison with a same-sized study without X-enrichment. With increasing interest in conducting secondary analyses to reduce research costs, caution should be employed when analyzing studies that have already been enriched, intentionally or unintentionally, for a primary exposure of interest. Causal diagrams can help identify scenarios in which secondary analyses may be biased. Inverse probability weights can be used to remove the bias.
C1 [Ahrens, K. A.; Schisterman, E. F.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Intramural Populat Hlth Res, Bethesda, MD USA.
[Cole, S. R.; Westreich, D.] Univ N Carolina, Dept Epidemiol, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA.
[Platt, R. W.] McGill Univ, Fac Med, Dept Epidemiol Biostat & Occupat Hlth, Montreal, PQ, Canada.
RP Schisterman, EF (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Intramural Populat Hlth Res, 6100 Execut Blvd,Room 7B03, Rockville, MD 20852 USA.
EM schistee@mail.nih.gov
OI Platt, Robert/0000-0002-5981-8443; Schisterman,
Enrique/0000-0003-3757-641X
FU Intramural Research Program of the Eunice Kennedy Shriver National
Institute of Child Health and Human Development, US National Institutes
of Health; National Institute of Allergy and Infectious Diseases, US
National Institutes of Health [R01-AI 100654]; Chercheur National Award
from the Fonds de Recherche en Sante du Quebec; Fonds de Recherche en
Sante du Quebec
FX This work was supported by the Intramural Research Program of the Eunice
Kennedy Shriver National Institute of Child Health and Human
Development, US National Institutes of Health (E.F.S. and K.A.A.); the
National Institute of Allergy and Infectious Diseases, US National
Institutes of Health (grant R01-AI 100654 to S.R.C.); the Chercheur
National Award from the Fonds de Recherche en Sante du Quebec (R.W.P.);
and core support provided to the Montreal Children's Hospital Research
Institute from the Fonds de Recherche en Sante du Quebec (R.W.P.).
NR 26
TC 2
Z9 2
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 FEB 1
PY 2015
VL 181
IS 3
BP 198
EP 203
DI 10.1093/aje/kwu276
PG 6
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA CB4XK
UT WOS:000349631500004
PM 25589243
ER
PT J
AU Wilcox, AJ
Weinberg, CR
Basso, O
Harmon, QE
AF Wilcox, Allen J.
Weinberg, Clarice R.
Basso, Olga
Harmon, Quaker E.
TI RE: "ANALYZING RISKS OF ADVERSE PREGNANCY OUTCOMES"
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Letter
C1 [Wilcox, Allen J.; Harmon, Quaker E.] NIEHS, Epidemiol Branch, Durham, NC 27713 USA.
[Weinberg, Clarice R.] NIEHS, Biostat Branch, Durham, NC USA.
[Basso, Olga] McGill Univ, Royal Victoria Hosp, Dept Obstet & Gynecol, Ctr Hlth, Montreal, PQ H3A 1A1, Canada.
[Basso, Olga] McGill Univ, Fac Med, Dept Epidemiol Biostat & Occupat Hlth, Montreal, PQ, Canada.
RP Wilcox, AJ (reprint author), NIEHS, Epidemiol Branch, Durham, NC 27713 USA.
EM wilcox@niehs.nih.gov
OI Harmon, Quaker/0000-0002-5866-848X; Wilcox, Allen/0000-0002-3376-1311
FU Intramural NIH HHS
NR 4
TC 1
Z9 1
U1 2
U2 3
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 FEB 1
PY 2015
VL 181
IS 3
BP 218
EP 218
DI 10.1093/aje/kwu463
PG 1
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA CB4XK
UT WOS:000349631500007
PM 25612573
ER
PT J
AU Yu, YK
Capra, JA
Stojmirovic, A
Landsman, D
Altschul, SF
AF Yu, Yi-Kuo
Capra, John A.
Stojmirovic, Aleksandar
Landsman, David
Altschul, Stephen F.
TI Log-odds sequence logos
SO BIOINFORMATICS
LA English
DT Article
ID ACID SUBSTITUTION MATRICES; CONSENSUS SEQUENCES; INFORMATION-CONTENT;
DIRICHLET MIXTURES; BINDING-SITES; PSI-BLAST; DNA; PROTEINS;
VISUALIZATION; ALIGNMENTS
AB Motivation: DNA and protein patterns are usefully represented by sequence logos. However, the methods for logo generation in common use lack a proper statistical basis, and are non-optimal for recognizing functionally relevant alignment columns.
Results: We redefine the information at a logo position as a per-observation multiple alignment log-odds score. Such scores are positive or negative, depending on whether a column's observations are better explained as arising from relatedness or chance. Within this framework, we propose distinct normalized maximum likelihood and Bayesian measures of column information. We illustrate these measures on High Mobility Group B (HMGB) box proteins and a dataset of enzyme alignments. Particularly in the context of protein alignments, our measures improve the discrimination of biologically relevant positions.
C1 [Yu, Yi-Kuo; Stojmirovic, Aleksandar; Landsman, David; Altschul, Stephen F.] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA.
[Capra, John A.] Vanderbilt Univ, Ctr Human Genet Res, Nashville, TN 37232 USA.
[Capra, John A.] Vanderbilt Univ, Dept Biomed Informat, Nashville, TN 37232 USA.
RP Altschul, SF (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA.
EM altschul@ncbi.nlm.nih.gov
OI Landsman, David/0000-0002-9819-6675
FU Intramural Research Program of the National Library of Medicine of the
National Institutes of Health; Vanderbilt University
FX Y.K.Y., A.S., D.L. and S.F.A. were supported by the Intramural Research
Program of the National Library of Medicine of the National Institutes
of Health; J.A.C. was supported by institutional funds from Vanderbilt
University.
NR 40
TC 2
Z9 2
U1 1
U2 6
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 FEB 1
PY 2015
VL 31
IS 3
BP 324
EP 331
DI 10.1093/bioinformatics/btu634
PG 8
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Computer Science, Interdisciplinary Applications; Mathematical &
Computational Biology; Statistics & Probability
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Computer Science; Mathematical & Computational Biology; Mathematics
GA CC0WG
UT WOS:000350058800005
PM 25294922
ER
PT J
AU Nakamura, N
Inselman, AL
White, GA
Chang, CW
Trbojevich, RA
Sephr, E
Voris, KL
Patton, RE
Bryant, MS
Harrouk, W
McIntyre, BS
Foster, PMD
Hansen, DK
AF Nakamura, Noriko
Inselman, Amy L.
White, Gene A.
Chang, Ching-Wei
Trbojevich, Raul A.
Sephr, Estatira
Voris, Kristie L.
Patton, Ralph E.
Bryant, Matthew S.
Harrouk, Wafa
McIntyre, Barry S.
Foster, Paul M. D.
Hansen, Deborah K.
TI Effects of Maternal and Lactational Exposure to
2-Hydroxy-4-Methoxybenzone on Development and Reproductive Organs in
Male and Female Rat Offspring
SO BIRTH DEFECTS RESEARCH PART B-DEVELOPMENTAL AND REPRODUCTIVE TOXICOLOGY
LA English
DT Article
DE 2-hydroxy-4-methoxybenzophenone; body weight; rats; offspring; testes;
ovary; fetal exposure
ID ENDOCRINE-DISRUPTING CHEMICALS; TANDEM MASS-SPECTROMETRY; BODY TOPICAL
APPLICATION; UV FILTERS; CELL APOPTOSIS; LIQUID-CHROMATOGRAPHY;
ESTROGENIC ACTIVITY; SURFACE WATERS; SWISS LAKES; BENZOPHENONE-3
AB BACKGROUND2-Hydroxy-4-methoxybenzophenone (HMB) is an ultraviolet (UV) absorbing compound used in many cosmetic products as a UV-protecting agent and in plastics for preventing UV-induced photodecomposition. HMB has been detected in over 95% of randomly collected human urine samples from adults and from premature infants, and it may have estrogenic potential.
METHODSTo determine the effects of maternal and lactational exposure to HMB on development and reproductive organs of offspring, time-mated female Harlan Sprague-Dawley rats were dosed with 0, 1000, 3000, 10,000, 25,000, or 50,000 ppm HMB (seven to eight per group) added to chow from gestation day 6 until weaning on postnatal day (PND) 23.
RESULTS AND CONCLUSIONExposure to HMB was associated with reduced body and organ weights in female and male offspring. No significant differences were observed in the number of implantation sites/litter, mean resorptions/litter, % litters with resorptions, number and weights of live fetuses, or sex ratios between the control and HMB dose groups. Normalized anogenital distance in male pups at PND 23 was decreased in the highest dose group. Spermatocyte development was impaired in testes of male offspring in the highest dose group. In females, follicular development was delayed in the highest dose group. However, by evaluating levels of the compound in rat serum, the doses at which adverse events occurred are much higher than usual human exposure levels. Thus, exposure to less than 10,000 ppm HMB does not appear to be associated with adverse effects on the reproductive system in rats
C1 [Nakamura, Noriko; Inselman, Amy L.; White, Gene A.; Hansen, Deborah K.] US FDA, Div Syst Biol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
[Chang, Ching-Wei] US FDA, Div Bioinformat & Biostat, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
[Trbojevich, Raul A.; Sephr, Estatira; Bryant, Matthew S.] US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
[Voris, Kristie L.; Patton, Ralph E.] Toxicol Pathol Associates, Jefferson, AR USA.
[Harrouk, Wafa] US FDA, Ctr Drug Evaluat & Res, Jefferson, AR 72079 USA.
[McIntyre, Barry S.; Foster, Paul M. D.] NIEHS, Natl Toxicol Program, NIH, Res Triangle Pk, NC 27709 USA.
RP Nakamura, N (reprint author), US FDA, Div Syst Biol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
EM Noriko.Nakamura@fda.hhs.gov
FU NCTR [E0745502]; FDA/NCTR [FDA 224-12-0003]; NIEHS/NTP [NIH AES12013]
FX Grant sponsor: NCTR; Grant number: E0745502; Grant sponsor: FDA/NCTR;
Grant number: FDA 224-12-0003; Grant sponsor: NIEHS/NTP; Grant number:
NIH AES12013.
NR 51
TC 2
Z9 2
U1 1
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1542-9733
EI 1542-9741
J9 BIRTH DEFECTS RES B
JI Birth Defects Res. Part B-Dev. Reprod. Toxicol.
PD FEB
PY 2015
VL 104
IS 1
BP 35
EP 51
DI 10.1002/bdrb.21137
PG 17
WC Oncology; Genetics & Heredity; Toxicology
SC Oncology; Genetics & Heredity; Toxicology
GA CC1ZX
UT WOS:000350145200004
PM 25707689
ER
PT J
AU Kabisch, M
Bermejo, JL
Duennebier, T
Ying, SB
Michailidou, K
Bolla, MK
Wang, Q
Dennis, J
Shah, M
Perkins, BJ
Czene, K
Darabi, H
Eriksson, M
Bojesen, SE
Nordestgaard, BG
Nielsen, SF
Flyger, H
Lambrechts, D
Neven, P
Peeters, S
Weltens, C
Couch, FJ
Olson, JE
Wang, XS
Purrington, K
Chang-Claude, J
Rudolph, A
Seibold, P
Flesch-Janys, D
Peto, J
dos-Santos-Silva, I
Johnson, N
Fletcher, O
Nevanlinna, H
Muranen, TA
Aittomaki, K
Blomqvist, C
Schmidt, MK
Broeks, A
Cornelissen, S
Hogervorst, FBL
Li, JM
Brand, JS
Humphreys, K
Guenel, P
Truong, T
Menegaux, F
Sanchez, M
Burwinkel, B
Marme, F
Yang, RX
Bugert, P
Gonzalez-Neira, A
Benitez, J
Zamora, MP
Perez, JIA
Cox, A
Cross, SS
Reed, MWR
Andrulis, IL
Knight, JA
Glendon, G
Tchatchou, S
Sawyer, EJ
Tomlinson, I
Kerin, MJ
Miller, N
Haiman, CA
Schumacher, F
Henderson, BE
Le Marchand, L
Lindblom, A
Margolin, S
Hooning, MJ
Hollestelle, A
Kriege, M
Koppert, LB
Hopper, JL
Southey, MC
Tsimiklis, H
Apicella, C
Slettedahl, S
Toland, AE
Vachon, C
Yannoukakos, D
Giles, GG
Milne, RL
McLean, C
Fasching, PA
Ruebner, M
Ekici, AB
Beckmann, MW
Brenner, H
Dieffenbach, AK
Arndt, V
Stegmaier, C
Ashworth, A
Orr, N
Schoemaker, MJ
Swerdlow, A
Garcia-Closas, M
Figueroa, J
Chanock, SJ
Lissowska, J
Goldberg, MS
Labreche, F
Dumont, M
Winqvist, R
Pylkas, K
Jukkola-Vuorinen, A
Grip, M
Brauch, H
Bruning, T
Ko, YD
Radice, P
Peterlongo, P
Scuvera, G
Fortuzzi, S
Bogdanova, N
Dork, T
Mannermaa, A
Kataja, V
Kosma, VM
Hartikainen, JM
Devilee, P
Tollenaar, RAEM
Seynaeve, C
Van Asperen, CJ
Jakubowska, A
Lubinski, J
Jaworska-Bieniek, K
Durda, K
Zheng, W
Shrubsole, MJ
Cai, QY
Torres, D
Anton-Culver, H
Kristensen, V
Bacot, F
Tessier, DC
Vincent, D
Luccarini, C
Baynes, C
Ahmed, S
Maranian, M
Simard, J
Chenevix-Trench, G
Hall, P
Pharoah, PDP
Dunning, AM
Easton, DF
Hamann, U
AF Kabisch, Maria
Bermejo, Justo Lorenzo
Duennebier, Thomas
Ying, Shibo
Michailidou, Kyriaki
Bolla, Manjeet K.
Wang, Qin
Dennis, Joe
Shah, Mitul
Perkins, Barbara J.
Czene, Kamila
Darabi, Hatef
Eriksson, Mikael
Bojesen, Stig E.
Nordestgaard, Borge G.
Nielsen, Sune F.
Flyger, Henrik
Lambrechts, Diether
Neven, Patrick
Peeters, Stephanie
Weltens, Caroline
Couch, Fergus J.
Olson, Janet E.
Wang, Xianshu
Purrington, Kristen
Chang-Claude, Jenny
Rudolph, Anja
Seibold, Petra
Flesch-Janys, Dieter
Peto, Julian
dos-Santos-Silva, Isabel
Johnson, Nichola
Fletcher, Olivia
Nevanlinna, Heli
Muranen, Taru A.
Aittomaki, Kristiina
Blomqvist, Carl
Schmidt, Marjanka K.
Broeks, Annegien
Cornelissen, Sten
Hogervorst, Frans B. L.
Li, Jingmei
Brand, Judith S.
Humphreys, Keith
Guenel, Pascal
Truong, Therese
Menegaux, Florence
Sanchez, Marie
Burwinkel, Barbara
Marme, Frederik
Yang, Rongxi
Bugert, Peter
Gonzalez-Neira, Anna
Benitez, Javier
Pilar Zamora, M.
Arias Perez, Jose I.
Cox, Angela
Cross, Simon S.
Reed, Malcolm W. R.
Andrulis, Irene L.
Knight, Julia A.
Glendon, Gord
Tchatchou, Sandrine
Sawyer, Elinor J.
Tomlinson, Ian
Kerin, Michael J.
Miller, Nicola
Haiman, Christopher A.
Schumacher, Fredrick
Henderson, Brian E.
Le Marchand, Loic
Lindblom, Annika
Margolin, Sara
Hooning, Maartje J.
Hollestelle, Antoinette
Kriege, Mieke
Koppert, Linetta B.
Hopper, John L.
Southey, Melissa C.
Tsimiklis, Helen
Apicella, Carmel
Slettedahl, Seth
Toland, Amanda E.
Vachon, Celine
Yannoukakos, Drakoulis
Giles, Graham G.
Milne, Roger L.
McLean, Catriona
Fasching, Peter A.
Ruebner, Matthias
Ekici, Arif B.
Beckmann, Matthias W.
Brenner, Hermann
Dieffenbach, Aida K.
Arndt, Volker
Stegmaier, Christa
Ashworth, Alan
Orr, Nicholas
Schoemaker, Minouk J.
Swerdlow, Anthony
Garcia-Closas, Montserrat
Figueroa, Jonine
Chanock, Stephen J.
Lissowska, Jolanta
Goldberg, Mark S.
Labreche, France
Dumont, Martine
Winqvist, Robert
Pylkas, Katri
Jukkola-Vuorinen, Arja
Grip, Mervi
Brauch, Hiltrud
Bruening, Thomas
Ko, Yon-Dschun
Radice, Paolo
Peterlongo, Paolo
Scuvera, Giulietta
Fortuzzi, Stefano
Bogdanova, Natalia
Doerk, Thilo
Mannermaa, Arto
Kataja, Vesa
Kosma, Veli-Matti
Hartikainen, Jaana M.
Devilee, Peter
Tollenaar, Robert A. E. M.
Seynaeve, Caroline
Van Asperen, Christi J.
Jakubowska, Anna
Lubinski, Jan
Jaworska-Bieniek, Katarzyna
Durda, Katarzyna
Zheng, Wei
Shrubsole, Martha J.
Cai, Qiuyin
Torres, Diana
Anton-Culver, Hoda
Kristensen, Vessela
Bacot, Francois
Tessier, Daniel C.
Vincent, Daniel
Luccarini, Craig
Baynes, Caroline
Ahmed, Shahana
Maranian, Mel
Simard, Jacques
Chenevix-Trench, Georgia
Hall, Per
Pharoah, Paul D. P.
Dunning, Alison M.
Easton, Douglas F.
Hamann, Ute
CA kConFab Investigators
Australian Ovarian Canc Study Grp
GENICA Network
TI Inherited variants in the inner centromere protein (INCENP) gene of the
chromosomal passenger complex contribute to the susceptibility of
ER-negative breast cancer
SO CARCINOGENESIS
LA English
DT Article
ID AURORA-B; CLEAVAGE FURROW; SURVIVIN; KINASE; CYTOKINESIS; MAMMAGLOBIN;
SEGREGATION; METAPHASE; MITOSIS; MIDBODY
AB The chromosomal passenger complex (CPC) plays a pivotal role in the regulation of cell division. Therefore, inherited CPC variability could influence tumor development. The present candidate gene approach investigates the relationship between single nucleotide polymorphisms (SNPs) in genes encoding key CPC components and breast cancer risk. Fifteen SNPs in four CPC genes (INCENP, AURKB, BIRC5 and CDCA8) were genotyped in 88 911 European women from 39 case-control studies of the Breast Cancer Association Consortium. Possible associations were investigated in fixed-effects meta-analyses. The synonymous SNP rs1675126 in exon 7 of INCENP was associated with overall breast cancer risk [per A allele odds ratio (OR) 0.95, 95% confidence interval (CI) 0.92-0.98, P = 0.007] and particularly with estrogen receptor (ER)-negative breast tumors (per A allele OR 0.89, 95% CI 0.83-0.95, P = 0.0005). SNPs not directly genotyped were imputed based on 1000 Genomes. The SNPs rs1047739 in the 3E(1) untranslated region and rs144045115 downstream of INCENP showed the strongest association signals for overall (per T allele OR 1.03, 95% CI 1.00-1.06, P = 0.0009) and ER-negative breast cancer risk (per A allele OR 1.06, 95% CI 1.02-1.10, P = 0.0002). Two genotyped SNPs in BIRC5 were associated with familial breast cancer risk (top SNP rs2071214: per G allele OR 1.12, 95% CI 1.04-1.21, P = 0.002). The data suggest that INCENP in the CPC pathway contributes to ER-negative breast cancer susceptibility in the European population. In spite of a modest contribution of CPC-inherited variants to the total burden of sporadic and familial breast cancer, their potential as novel targets for breast cancer treatment should be further investigated.
C1 [Kabisch, Maria; Duennebier, Thomas; Ying, Shibo; Torres, Diana; Hamann, Ute] German Canc Res Ctr, Mol Genet Breast Canc, D-69120 Heidelberg, Germany.
[Bermejo, Justo Lorenzo] Univ Heidelberg Hosp, Inst Med Biometry & Informat, D-69120 Heidelberg, Germany.
[Michailidou, Kyriaki; Bolla, Manjeet K.; Wang, Qin; Dennis, Joe] Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Publ Hlth & Primary Care, Cambridge CB1 8RN, England.
[Shah, Mitul; Perkins, Barbara J.; Luccarini, Craig; Baynes, Caroline; Ahmed, Shahana; Maranian, Mel; Dunning, Alison M.] Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Oncol, Cambridge CB1 8RN, England.
[Czene, Kamila; Darabi, Hatef; Eriksson, Mikael; Brand, Judith S.; Humphreys, Keith; Hall, Per] Karolinska Inst, Dept Med Epidemiol & Biostat, SE-17177 Stockholm, Sweden.
[Bojesen, Stig E.; Nordestgaard, Borge G.; Nielsen, Sune F.] Copenhagen Univ Hosp, Copenhagen Gen Populat Study, Herlev Hosp, DK-2730 Herlev, Denmark.
[Bojesen, Stig E.; Nordestgaard, Borge G.; Nielsen, Sune F.] Copenhagen Univ Hosp, Dept Clin Biochem, Herlev Hosp, DK-2730 Herlev, Denmark.
[Flyger, Henrik] Copenhagen Univ Hosp, Dept Breast Surg, Herlev Hosp, DK-2730 Herlev, Denmark.
[Lambrechts, Diether] VIB, Vesalius Res Ctr, B-3000 Leuven, Belgium.
[Lambrechts, Diether] Univ Leuven, Lab Translat Genet, Dept Oncol, B-3000 Leuven, Belgium.
[Neven, Patrick; Peeters, Stephanie; Weltens, Caroline] Univ Leuven, KU Leuven, Dept Oncol, Multidisciplinary Breast Ctr,Univ Hosp Leuven, B-3000 Leuven, Belgium.
[Couch, Fergus J.; Wang, Xianshu] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN 55905 USA.
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[Purrington, Kristen] Karmanos Canc Inst, Detroit, MI 48201 USA.
[Chang-Claude, Jenny; Rudolph, Anja; Seibold, Petra] German Canc Res Ctr, Div Canc Epidemiol, D-69120 Heidelberg, Germany.
[Flesch-Janys, Dieter] Univ Clin Hamburg Eppendorf, Clin Canc Registry, Dept Canc Epidemiol, D-20246 Hamburg, Germany.
[Flesch-Janys, Dieter] Univ Clin Hamburg Eppendorf, Inst Med Biometr & Epidemiol, D-20246 Hamburg, Germany.
[Peto, Julian; dos-Santos-Silva, Isabel] Univ London London Sch Hyg & Trop Med, Dept Noncommunicable Dis Epidemiol, London WC1E 7HT, England.
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[Nevanlinna, Heli; Muranen, Taru A.] Univ Helsinki, Dept Obstet & Gynecol, FI-00029 Helsinki, Finland.
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[Cox, Angela; Reed, Malcolm W. R.] Univ Sheffield, Dept Oncol, Sheffield S10 2RX, S Yorkshire, England.
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[Tomlinson, Ian] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.
[Tomlinson, Ian] Univ Oxford, Oxford Biomed Res Ctr, Oxford OX3 7BN, England.
[Kerin, Michael J.; Miller, Nicola] Univ Hosp Galway, Clin Sci Inst, Galway, Ireland.
[kConFab Investigators] Peter MacCallum Canc Ctr, Melbourne, Vic 3002, Australia.
[Australian Ovarian Canc Study Grp] QIMR Berghofer Med Res Inst, Brisbane, Qld 4006, Australia.
[Haiman, Christopher A.; Schumacher, Fredrick; Henderson, Brian E.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA.
[Le Marchand, Loic] Univ Hawaii, Ctr Canc, Epidemiol Program, Honolulu, HI 96813 USA.
[Lindblom, Annika] Karolinska Inst, Dept Mol Med & Surg, SE-17177 Stockholm, Sweden.
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[Hooning, Maartje J.; Hollestelle, Antoinette; Kriege, Mieke; Seynaeve, Caroline] Erasmus MC Canc Inst, Dept Med Oncol, NL-3008 AE Rotterdam, Netherlands.
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[Hopper, John L.; Apicella, Carmel; Giles, Graham G.; Milne, Roger L.] Univ Melbourne, Melbourne Sch Populat & Global Hlth, Ctr Epidemiol & Biostat, Melbourne, Vic 3010, Australia.
[Southey, Melissa C.; Tsimiklis, Helen] Univ Melbourne, Dept Pathol, Melbourne, Vic 3010, Australia.
[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, IRRP, Mol Diagnost Lab, Aghia Paraskevi Attikis, Athens 15310, Greece.
[Giles, Graham G.; Milne, Roger L.] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic 3053, Australia.
[McLean, Catriona] Alfred Hosp, Anat Pathol, Melbourne, Vic 3004, Australia.
[Fasching, Peter A.; Ruebner, Matthias; Beckmann, Matthias W.] Univ Erlangen Nurnberg, Univ Hosp Erlangen, Univ Breast Ctr Franconia, Dept Gynecol & Obstet, D-91054 Erlangen, Germany.
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[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, Univ Hosp Erlangen, Inst Human Genet, D-91054 Erlangen, Germany.
[Brenner, Hermann; Dieffenbach, Aida K.; Arndt, Volker] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, D-69120 Heidelberg, Germany.
[Brenner, Hermann; Dieffenbach, Aida K.] German Canc Consortium DKTK, D-69120 Heidelberg, Germany.
[Stegmaier, Christa] Saarland Canc Registry, D-66119 Saarbrucken, Germany.
[Schoemaker, Minouk J.; Swerdlow, Anthony; Garcia-Closas, Montserrat] Inst Canc Res, Div Genet & Epidemiol, Sutton SM2 5NG, Surrey, England.
[Swerdlow, Anthony] Inst Canc Res, Div Breast Canc Res, Sutton SM2 5NG, Surrey, England.
[Figueroa, Jonine; Chanock, Stephen J.] NCI, Div Canc Epidemiol & Genet, Rockville, MD 20850 USA.
[Lissowska, Jolanta] M Sklodowska Curie Mem Canc Ctr, Dept Canc Epidemiol & Prevent, PL-02781 Warsaw, Poland.
[Lissowska, Jolanta] Inst Oncol, PL-02781 Warsaw, Poland.
[Goldberg, Mark S.] McGill Univ, Dept Med, Montreal, PQ H3G 2M1, Canada.
[Goldberg, Mark S.] Royal Victoria Hosp, McGill Univ Hlth Ctr, Div Clin Epidemiol, Montreal, PQ H3G 2M1, Canada.
[Labreche, France] Univ Montreal, Ecole Sante Publ, Dept Med Sociale & Prevent, Dept Sante Environm & Sante Travail, Montreal, PQ H3T 1A8, Canada.
[Dumont, Martine; Simard, Jacques] Ctr Hosp Univ Quebec, Res Ctr, Quebec City, PQ G1V 4G2, Canada.
[Dumont, Martine; Simard, Jacques] Univ Laval, Quebec City, PQ G1V 4G2, Canada.
[Winqvist, Robert; Pylkas, Katri] Univ Oulu, Lab Canc Genet & Tumor Biol, Oulu Univ Hosp, Dept Clin Chem,NordLab Oulu, FI-90220 Oulu, Finland.
[Winqvist, Robert; Pylkas, Katri] Univ Oulu, Lab Canc Genet & Tumor Biol, Oulu Univ Hosp, Bioctr Oulu,NordLab Oulu, FI-90220 Oulu, Finland.
[Jukkola-Vuorinen, Arja] Univ Oulu, Oulu Univ Hosp, Dept Oncol, FI-90220 Oulu, Finland.
[Grip, Mervi] Univ Oulu, Oulu Univ Hosp, Dept Surg, FI-90220 Oulu, Finland.
[Brauch, Hiltrud] Dr Margarete Fischer Bosch Inst Clin Pharmacol, D-70376 Stuttgart, Germany.
[Brauch, Hiltrud] Univ Tubingen, D-72074 Tubingen, Germany.
[Brauch, Hiltrud] German Canc Consortium DKTK, D-69120 Heidelberg, Germany.
[Brauch, Hiltrud] German Canc Res Ctr, D-69120 Heidelberg, Germany.
[Bruening, Thomas] Inst Ruhr Univ Bochum IPA, Inst Prevent & Occupat Med German Social Accident, D-44789 Bochum, Germany.
[Ko, Yon-Dschun] Evangel Kliniken Bonn gGmbH, Johanniter Krankenhaus, Dept Internal Med, D-53113 Bonn, Germany.
Univ Bonn, Fac Med, Inst Pathol, D-53127 Bonn, Germany.
[GENICA Network] Univ Med Ctr Hamburg Eppendorf, Inst Occupat Med & Maritime Med, D-20246 Hamburg, Germany.
[Radice, Paolo] Fdn IRCCS Ist Nazl Tumori INT, Dept Prevent & Predict Med, Unit Mol Bases Genet Risk & Genet Testing, I-20133 Milan, Italy.
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[Fortuzzi, Stefano] Cogentech Canc Genet Test Lab, I-20139 Milan, Italy.
[Bogdanova, Natalia] Hannover Med Sch, Dept Radiat Oncol, D-30625 Hannover, Germany.
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[Mannermaa, Arto; Kosma, Veli-Matti; Hartikainen, Jaana M.] Univ Eastern Finland, Inst Clin Med Pathol & Forens Med, Sch Med, FI-70211 Kuopio, Finland.
[Mannermaa, Arto; Kosma, Veli-Matti; Hartikainen, Jaana M.] Univ Eastern Finland, Canc Ctr Eastern Finland, FI-70211 Kuopio, Finland.
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[Kataja, Vesa] Kuopio Univ Hosp, Ctr Canc, FI-70210 Kuopio, Finland.
[Kataja, Vesa] Jyvaskyla Cent Hosp, FI-40620 Jyvaskyla, Finland.
[Devilee, Peter] Leiden Univ, Med Ctr, Dept Human Genet, NL-2333 ZC Leiden, Netherlands.
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[Jakubowska, Anna; Lubinski, Jan; Jaworska-Bieniek, Katarzyna; Durda, Katarzyna] Pomeranian Med Univ, Dept Genet & Pathol, PL-70115 Szczecin, Poland.
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[Bacot, Francois; Tessier, Daniel C.; Vincent, Daniel] McGill Univ, Montreal, PQ H3A 0G1, Canada.
[Bacot, Francois; Tessier, Daniel C.; Vincent, Daniel] McGill Univ, Montreal, PQ H3A 0G1, Canada.
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[Chenevix-Trench, Georgia] QIMR Berghofer Med Res Inst, Dept Genet, Brisbane, Qld 4006, Australia.
RP Hamann, U (reprint author), German Canc Res Ctr, Mol Genet Breast Canc B072, Neuenheimer Feld 580, D-69120 Heidelberg, Germany.
EM u.hamann@dkfz-heidelberg.de
RI Shrubsole, Martha/K-5052-2015; Dork, Thilo/J-8620-2012; Bowtell,
David/H-1007-2016; Bruning, Thomas/G-8120-2015; Andrulis,
Irene/E-7267-2013; Brenner, Hermann/B-4627-2017; Gonzalez-Neira,
Anna/C-5791-2015; Hartikainen, Jaana/E-6256-2015; Li,
Jingmei/I-2904-2012; Garcia-Closas, Montserrat /F-3871-2015; Knight,
Julia/A-6843-2012;
OI Shrubsole, Martha/0000-0002-5591-7575; Bowtell,
David/0000-0001-9089-7525; Bruning, Thomas/0000-0001-9560-5464; Brenner,
Hermann/0000-0002-6129-1572; Fortuzzi, Stefano/0000-0002-5662-3800;
Schoemaker, Minouk/0000-0001-8403-2234; Li, Jingmei/0000-0001-8587-7511;
Garcia-Closas, Montserrat /0000-0003-1033-2650; Czene,
Kamila/0000-0002-3233-5695; Cross, Simon/0000-0003-2044-1754; Dunning,
Alison Margaret/0000-0001-6651-7166; dos Santos Silva,
Isabel/0000-0002-6596-8798; Ying, Shibo/0000-0001-5275-9383; Cox,
Angela/0000-0002-5138-1099; Yannoukakos, Drakoulis/0000-0001-7509-3510;
Giles, Graham/0000-0003-4946-9099; Muranen, Taru/0000-0002-5895-1808
FU National Health and Medical Research Council; National Breast Cancer
Foundation; Cancer Australia; National Institute of Health (USA); Cancer
Research UK [C1287/A10118, C1287/A12014, C1287/A 10710, C12292/A11174,
C1281/A12014, C5047/A8384, C5047/A15007, C5047/A10692, C490/A10124];
European Community [223175, HEALTH-F2-2009-223175, 223175
(HEALTH-F2-2009-223175)]; National Institutes of Health [CA128978];
Post-Cancer GWAS initiative (GAME-ON 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; UK National
Institute for Health Research Biomedical Research Centre at the
University of Cambridge; Marit and Hans Rausings Initiative Against
Breast Cancer.; Chief Physician Johan Boserup and Lise Boserup Fund;
Danish Medical Research Council and Herlev Hospital; 'Stichting tegen
Kanker' [232-2008, 196-2010]; FWO; NIH [CA128978, CA116167, CA176785,
CA116201, CA63464, CA54281, CA098758, CA132839]; Deutsche Krebshilfe
e.V. [70-2892-BR I]; Hamburg Cancer Society; German Cancer Research
Center; Federal Ministry of Education and Research (BMBF) Germany
[01KH0402]; Cancer Research UK; Breakthrough Breast Cancer; NHS;
National Cancer Research Network (NCRN); Helsinki University Central
Hospital Research Fund; Academy of Finland [266528]; Finnish Cancer
Society; Nordic Cancer Union; Sigrid Juselius Foundation; Dutch Cancer
Society [NKI 2007-3839, 2009 4363]; Dutch government [NWO 184.021.007];
Dutch National Genomics Initiative; Asociacion Espanola Contra el
Cancer; Fondo de Investigacion Sanitario [PI11/00923, PI081120];
Instituto de Salud Carlos III; Oxford Biomedical Research Centre;
Stockholm County Council; Karolinska Institutet; Swedish Cancer Society;
Gustav V Jubilee foundation; Bert von Kantzows foundation; National
Cancer Institute (USA) [UM1 CA164920]; NHMRC of Australia; New South
Wales Cancer Council; Victorian Health Promotion Foundation (Australia);
Victorian Breast Cancer Research Consortium; CCSG Share Resource by
National Institutes of Health [P30 CA016056]; Hellenic Cooperative
Oncology Group [HR R_BG/04]; Australian NHMRC [209057, 251553, 504711];
German Cancer Aid (Deutsche Krebshilfe); Canadian Institutes of Health
Research [CRN-87521]; Ministry of Economic Development, Innovation and
Export Trade [PSR-SIIRI-701]; Finnish Cancer Foundation, the Academy of
Finland [250083, 122715]; Finnish Cancer Foundation, the Academy of
Finland (Center of Excellence) [251314]; Finnish Cancer Foundation;
Federal Ministry of Education and Research (BMBF) [01KW9975/5,
01KW9976/8, 01KW9977/0, 01KW0114]; Fondazione IRCCS Istituto Nazionale
Tumori; Government Funding (EVO) of Kuopio University Hospital; Cancer
Fund of North Savo; Finnish Cancer Organizations; University of Eastern
Finland; NIH grant [R01CA100374, R01 CA77398]; California Breast Cancer
Research Fund [97-10500]; California Department of Public Health
[103885]; Lon V Smith Foundation [LVS39420]; Norwegian Research council
[155218/V40, 175240/S10, FUGE-NFR 181600/V11]; Swizz Bridge Award;
[KULPFV/10/016-SymBioSysII]; [PBZ_KBN_122/P05/2004]; [P30 CA68485];
Associazione Italiana per la Ricerca sul Cancro
FX The results shown in this article are in part based upon data generated
by the TCGA Research Network: http://cancergenome.nih.gov; the ENCODE
Consortium and the ENCODE production laboratory(s):
http://genome.ucsc.edu/ENCODE; the Gene Expression Omnibus contributors:
http://www.ncbi.nlm.nih.gov/geo and the 1000 Genomes Project Consortium:
http://www.1000genomes.org/home.BCAC: We thank all the individuals who
took part in these studies and all the researchers, clinicians,
technicians and administrative staff who have enabled this work to be
carried out. COGS: This study would not have been possible without the
contributions of the following: PH (COGS); DFE, PP, KM, MKB, QW (BCAC),
Andrew Berchuck (OCAC), Rosalind A. Eeles, DFE, Ali Amin Al Olama,
Zsofia Kote-Jarai, Sara Benlloch (PRACTICAL), GCT, Antonis Antoniou,
Lesley McGuffog, FJC and Ken Offit (CIMBA), JD, AMD, Andrew Lee, and Ed
Dicks, CL and the staff of the Centre for Genetic Epidemiology
Laboratory, JB, AGN and the staff of the CNIO genotyping unit, JS and
DCT, FB, DV, Sylvie LaBoissiere and Frederic Robidoux and the staff of
the McGill University and Genome Quebec Innovation Centre, SEB, SFN,
BGN, and the staff of the Copenhagen DNA laboratory, and Julie M.
Cunningham, Sharon A. Windebank, Christopher A. Hilker, Jeffrey Meyer
and the staff of Mayo Clinic Genotyping Core Facility. SEARCH: The
SEARCH and EPIC teams. pKARMA: The Swedish Medical Research Counsel.
CGPS: Staff and participants of the Copenhagen General Population Study.
For the excellent technical assistance: Dorthe Uldall Andersen, Maria
Birna Arnadottir, Anne Bank, Dorthe Kjeldgard Hansen. The Danish Breast
Cancer Group (DBCG) is acknowledged for the tumor information. LMBC:
Gilian Peuteman, Dominiek Smeets, Thomas Van Brussel and Kathleen
Corthouts. MARIE: Judith Heinz, Nadia Obi, Alina Vrieling, Sabine
Behrens, Ursula Eilber, Muhabbet Celik, Til Olchers, Stefan Nickels.
BBCS: Eileen Williams, Elaine Ryder-Mills, Kara Sargus. HEBCS: Kirsimari
Aaltonen, Karl von Smitten, Sofia Khan, Tuomas Heikkinen, Irja Erkkila.
ABCS: Sten Cornelissen, Richard van Hien, Linde Braaf, FBLH, Senno
Verhoef, Laura van 't Veer, Emiel Rutgers, Ellen van der Schoot, Femke
Atsma. SASBAC: The Swedish Medical Research Counsel. BSUCH: Medical
Faculty Mannheim, Germany (PB). CNIO-BCS: Guillermo Pita, Charo Alonso,
Daniel Herrero, Nuria Alvarez, MPZ, Primitiva Menendez, the Human
Genotyping-CEGEN Unit (CNIO). SBCS: Sue Higham, Helen Cramp, Ian Brock,
Sabapathy Balasubramanian and Dan Connley. OFBCR: Teresa Selander,
Nayana Weerasooriya. BIGGS: Niall McInerney, Gabrielle Colleran, Andrew
Rowan, Angela Jones. kConFab/AOCS: We wish to thank Heather Thorne,
Eveline Niedermayr, all the kConFab research nurses and staff, the heads
and staff of the Family Cancer Clinics, and the Clinical Follow Up Study
(which has received funding from the National Health and Medical
Research Council, the National Breast Cancer Foundation, Cancer
Australia and the National Institute of Health (USA) for their
contributions to this resource, and the many families who contribute to
kConFab. RBCS: Petra Bos, Jannet Blom, Ellen Crepin, Anja Nieuwlaat,
Annette Heemskerk, the Erasmus MC Family Cancer Clinic. ABCFS: Maggie
Angelakos, Judi Maskiell, Gillian Dite. TNBCC: Robert Pilarski and
Charles Shapiro were instrumental in the formation of the OSU Breast
Cancer Tissue Bank. We thank the Human Genetics Sample Bank for
processing of samples and providing OSU Columbus area control samples.
BBCC: Silke Landrith, Alexander Hein, Sonja Oeser, Michael Schneider.;
ESTHER: Hartwig Ziegler, Sonja Wolf, Volker Hermann. UKBGS: We thank
Breakthrough Breast Cancer and the Institute of Cancer Research for
support and funding of the Breakthrough Generations Study, and the study
participants, study staff, and the doctors, nurses and other health care
providers and health information sources who have contributed to the
study. We acknowledge National Health Service (NHS) funding to the Royal
Marsden/ICR NIHR Biomedical Research Centre. PBCS: Louise Brinton, Mark
Sherman, Neonila Szeszenia-Dabrowska, Beata Peplonska, Witold Zatonski,
Pei Chao, Michael Stagner. MTLGEBCS: We would like to thank Martine
Tranchant (CHU de Quebec Research Center), Marie-France Valois, Annie
Turgeon and Lea Heguy (McGill University Health Centre, Royal Victoria
Hospital; McGill University) for DNA extraction, sample management and
skillful technical assistance. J.S. is Chairholder of the Canada
Research Chair in Oncogenetics. OBCS: Meeri Otsukka, Kari Mononen.
GENICA: The GENICA Network: Dr Margarete Fischer-Bosch-Institute of
Clinical Pharmacology, Stuttgart, and University of Tubingen, Germany;
(HBra, Wing-Yee Lo, Christina Justenhoven), Department of Internal
Medicine, Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus,
Bonn, Germany (YDK, Christian Baisch), Institute of Pathology,
University of Bonn, Germany (Hans-Peter Fischer), Molecular Genetics of
Breast Cancer, Deutsches Krebsforschungszentrum (DKFZ), Heidelberg,
Germany (UH) and Institute for Prevention and Occupational Medicine of
the German Social Accident Insurance, Institute of the Ruhr University
Bochum (IPA), Bochum, Germany (TB, Beate Pesch, Sylvia Rabstein, Anne
Lotz); Institute of Occupational Medicine and Maritime Medicine,
University Medical Center Hamburg-Eppendorf, Germany (Volker Harth).
MBCSG: Siranoush Manoukian, Bernard Peissel and Daniela Zaffaroni of the
Fondazione IRCCS Istituto Nazionale dei Tumori (INT); Bernardo Bonanni,
Monica Barile and Irene Feroce of the Istituto Europeo di Oncologia
(IEO) and Loris Bernard the personnel of the Cogentech Cancer Genetic
Test Laboratory. HMBCS: Peter Hillemanns, Hans Christiansen and Johann
H. Karstens. KBCP: Eija Myohanen, Helena Kemilainen. ORIGO: We thank E.
Krol-Warmerdam and J. Blom for patient accrual, administering
questionnaires and managing clinical information. The LUMC survival data
were retrieved from the Leiden hospital-based cancer registry system
(ONCDOC) with the help of Dr J. Molenaar. NBHS: We thank study
participants and research staff for their contributions and commitment
to this study. SKKDKFZS: We thank all study participants, clinicians,
family doctors, researchers and technicians for their contributions and
commitment to this study. CTS: The CTS Steering Committee includes
Leslie Bernstein, Susan Neuhausen, James Lacey, Sophia Wang, Huiyan Ma,
Yani Lu and Jessica Clague DeHart at the Beckman Research Institute of
City of Hope, Dennis Deapen, Rich Pinder, Eunjung Lee and Fred
Schumacher at the University of Southern California, Pam Horn-Ross,
Peggy Reynolds, Christina Clarke Dur and David Nelson at the Cancer
Prevention Institute of California, and HAC, Argyrios Ziogas, and Hannah
Park at the University of California Irvine. NBCS: NBCS includes the
following clinical collaborators: Prof. Per Eystein Lonning, MD (Section
of Oncology, Institute of Medicine, University of Bergen and Department
of Oncology, Haukeland University Hospital, Bergen, Norway), Prof. Em.
Sophie D.; Fossa, MD (National Resource Centre for Longterm Studies
after Cancer, Rikshospitalet-Radiumhospitalet Cancer Clinic Montebello,
Oslo, Norway), Head physician Tone Ikdahl, MD (Department of Oncology,
Oslo University Hospital, Oslo, Norway), Dr Lars Ottestad, MD
(Department of Genetics and Department of Oncology, Oslo University
Hospital Radiumhospitalet), Dr Marit Muri Holmen, MD (Department of
Radiology, Oslo University Hospital Radiumhospitalet, Oslo, Norway), Dr
Vilde Haakensen, MD (Department of Genetics and Department of Oncology,
Oslo University Hospital Radiumhospitalet and Institute for Clinical
Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway), Prof.
Bjorn Naume, MD (Division of Cancer Medicine and Radiotherapy,
Department of Oncology, Oslo University Hospital Radiumhospitalet, Oslo,
Norway), Associate Prof. Aslaug Helland, MD (Department of Genetics,
Institute for Cancer Research and Department of Oncology, Oslo
University Hospital Radiumhospitalet, Oslo, Norway and Institute of
Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo,
Norway), Prof. Inger Torhild Gram, MD (Department of Community Medicine,
Faculty of Health Sciences, University of Tromso and Norwegian Centre
for Integrated Care and Telemedicine, University Hospital of North
Norway, Tromso, Norway), Prof. Em. Rolf Karesen, MD (Department of
Breast and Endocrine Surgery, Institute for Clinical Medicine, Ullevaal
Hospital, Oslo University Hospital and Institute of Clinical Medicine,
Faculty of Medicine, University of Oslo, Oslo, Norway), Dr Ellen
Schlichting, MD (Department for Breast and Endocrine Surgery, Oslo
University Hospital Ullevaal, Oslo, Norway), Prof. Toril Sauer, MD
(Department of Pathology at Akershus University Hospital, Lorenskog,
Norway), Dr Olav Engebraten, MD (Institute for Clinical Medicine,
Faculty of Medicine, University of Oslo and Department of Oncology, Oslo
University Hospital, Oslo, Norway), Dr Margit Riis, MD (Department of
Surgery, Akershus University Hospital and Department of Clinical
Molecular Biology (EpiGen), Institute of Clinical Medicine, Akershus
University Hospital, University of Oslo, Lorenskog, Norway).; This work
was supported by the following: BCAC: Cancer Research UK [C1287/A10118,
C1287/A12014] and by the European Community's Seventh Framework
Programme under grant agreement number 223175 (grant number
HEALTH-F2-2009-223175) (COGS). iCOGS: the European Community's Seventh
Framework Programme under grant agreement no 223175
(HEALTH-F2-2009-223175) (COGS), Cancer Research UK (C1287/A10118,
C1287/A 10710, C12292/A11174, C1281/A12014, 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. SEARCH: Cancer Research UK [C490/A10124] and UK
National Institute for Health Research Biomedical Research Centre at the
University of Cambridge. pKARMA: Marit and Hans Rausings Initiative
Against Breast Cancer. CGPS: Chief Physician Johan Boserup and Lise
Boserup Fund, the Danish Medical Research Council and Herlev Hospital.
LMBC: 'Stichting tegen Kanker' (232-2008 and 196-2010). D.L. is
supported by the FWO and the KULPFV/10/016-SymBioSysII. MCBCS: NIH
grants CA128978, CA116167, CA176785 an NIH Specialized Program of
Research Excellence (SPORE) in Breast Cancer [CA116201], and 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. MARIE: 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]. BBCS: Cancer Research UK and Breakthrough
Breast Cancer and acknowledges NHS funding to the NIHR Biomedical
Research Centre, and the National Cancer Research Network (NCRN). HEBCS:
Helsinki University Central Hospital Research Fund, Academy of Finland
(266528), the Finnish Cancer Society, The Nordic Cancer Union and the
Sigrid Juselius Foundation. ABCS: Dutch Cancer Society [grants NKI
2007-3839 and 2009 4363]; BBMRI-NL, which is a Research Infrastructure
financed by the Dutch government (NWO 184.021.007); and the Dutch
National Genomics Initiative. SASBAC: Agency for Science, Technology and
Research of Singapore (A*STAR), the United States National Institute of
Health (NIH) and the Susan G. Komen Breast Cancer Foundation. CECILE:
Fondation de France, Institut National du Cancer (INCa), Ligue Nationale
contre le Cancer, Ligue contre le Cancer Grand Ouest, Agence Nationale
de Securite Sanitaire (ANSES), Agence Nationale de la Recherche (ANR).
BSUCH: Dietmar-Hopp Foundation, the Helmholtz Society and the German
Cancer Research Center (DKFZ). CNIO-BCS: Genome Spain Foundation, the
Red Tematica de Investigacion Cooperativa en Cancer and grants from the
Asociacion Espanola Contra el Cancer and the Fondo de Investigacion
Sanitario (PI11/00923 and PI081120). The Human Genotyping-CEGEN Unit
(CNIO) is supported by the Instituto de Salud Carlos III. SBCS:
Yorkshire Cancer Research S295, S299, S305PA and Sheffield Experimental
Cancer Medicine Centre. Ontario Familial Breast Cancer Registry (OFBCR):
UM1 CA164920 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 (BCFR), nor does mention of trade names,
commercial products or organizations imply endorsement by the USA
Government or the BCFR. BIGGS ES: NIHR Comprehensive Biomedical Research
Centre, Guy's and St. Thomas' NHS Foundation Trust in partnership with
King's College London, UK. I. T. is supported by the Oxford Biomedical
Research Centre. kConFab: National Breast Cancer Foundation, and
previously by the National Health and Medical Research Council (NHMRC),
the Queensland Cancer Fund, the Cancer Councils of New South Wales,
Victoria, Tasmania and South Australia, and the Cancer Foundation of
Western Australia. MEC: NIH grants CA63464, CA54281, CA098758 and
CA132839. Financial support for KARBAC was provided through the regional
agreement on medical training and clinical research (ALF) between
Stockholm County Council and Karolinska Institutet, the Swedish Cancer
Society, The Gustav V Jubilee foundation and Bert von Kantzows
foundation. RBCS: Dutch Cancer Society (DDHK 2004-3124, DDHK 2009-4318).
The Australian Breast Cancer Family Study (ABCFS) was supported by grant
UM1 CA164920 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 (BCFR), nor does mention of trade names,
commercial products or organizations imply endorsement by the USA
Government or the BCFR. The ABCFS was also supported by the NHMRC 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 NHMRC Australia Fellow and a Victorian
Breast Cancer Research Consortium Group Leader. M.C.S. is a NHMRC senior
research fellow and a Victorian Breast Cancer Research Consortium Group
Leader. TNBCC: Specialized Program of Research Excellence (SPORE) in
Breast Cancer (CA116201), a grant from the Breast Cancer Research
Foundation, a generous gift from the David F. and Margaret T. Grohne
Family Foundation and the Ting Tsung and Wei Fong Chao Foundation, the
Stefanie Spielman Breast Cancer fund and the OSU Comprehensive Cancer
Center, DBBR (a CCSG Share Resource by National Institutes of Health
Grant P30 CA016056), the Hellenic Cooperative Oncology Group research
grant (HR R_BG/04) and the Greek General Secretary for Research and
Technology (GSRT) Program, Research Excellence II, 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)-ARISTEIA. 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. BBCC:
ELAN-Fond of the University Hospital of Erlangen. ESTHER: Baden
Wurttemberg 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). UKBGS:
Breakthrough Breast Cancer and the Institute of Cancer Research (ICR),
London. ICR acknowledges NHS funding to the NIHR Biomedical Research
Centre. PBCS: Intramural Research Funds of the National Cancer
Institute, Department of Health and Human Services, USA.; MTLGEBCS:
Quebec Breast Cancer Foundation, the Canadian Institutes of Health
Research for the 'CIHR Team in Familial Risks of Breast Cancer'
program-grant # CRN-87521 and the Ministry of Economic Development,
Innovation and Export Trade-grant # PSR-SIIRI-701. OBCS: Finnish Cancer
Foundation, the Academy of Finland (grant number 250083, 122715 and
Center of Excellence grant number 251314), the Finnish Cancer
Foundation, the Sigrid Juselius Foundation, the University of Oulu, the
University of Oulu Support Foundation and the special Governmental EVO
funds for Oulu University Hospital-based research activities. GENICA:
Federal Ministry of Education and Research (BMBF) Germany grants
01KW9975/5, 01KW9976/8, 01KW9977/0 and 01KW0114, the Robert Bosch
Foundation, Stuttgart, Deutsches Krebsforschungszentrum (DKFZ),
Heidelberg, the Institute for Prevention and Occupational Medicine of
the German Social Accident Insurance, Institute of the Ruhr University
Bochum (IPA), Bochum, as well as the Department of Internal Medicine,
Evangelische Kliniken Bonn gGmbH, Johanniter Krankenhaus, Bonn, Germany.
MBCSG: Italian Association for Cancer Research (AIRC) and by funds from
the Italian citizens who allocated the 5/1000 share of their tax payment
in support of the Fondazione IRCCS Istituto Nazionale Tumori, according
to Italian laws (INT-Institutional strategic projects '5 x 1000').
HMBCS: Friends of Hannover Medical School and by the Rudolf Bartling
Foundation. KBCP: Government Funding (EVO) of Kuopio University Hospital
grants, Cancer Fund of North Savo, the Finnish Cancer Organizations and
by the strategic funding of the University of Eastern Finland. ORIGO:
Dutch Cancer Society (RUL 1997-1505) and the Biobanking and Biomolecular
Resources Research Infrastructure (BBMRI-NL CP16). The SZBCS was
supported by grant PBZ_KBN_122/P05/2004. NBHS: NIH grant R01CA100374.
Biological sample preparation was conducted the Survey and Biospecimen
Shared Resource, which is supported by P30 CA68485. SKKDKFZS: DKFZ. CTS:
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. HAC receives support
from the Lon V Smith Foundation (LVS39420). NBCS: Norwegian Research
council, 155218/V40, 175240/S10 to ALBD, FUGE-NFR 181600/V11 to VNK and
a Swizz Bridge Award to ALBD.
NR 51
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U1 2
U2 18
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0143-3334
EI 1460-2180
J9 CARCINOGENESIS
JI Carcinogenesis
PD FEB
PY 2015
VL 36
IS 2
BP 256
EP 271
DI 10.1093/carcin/bgu326
PG 16
WC Oncology
SC Oncology
GA CC2ZX
UT WOS:000350214900010
PM 25586992
ER
PT J
AU Musani, SK
Fox, ER
Kraja, A
Bidulescu, A
Lieb, W
Lin, HH
Beecham, A
Chen, MH
Felix, JF
Fox, CS
Kao, WHL
Kardia, SLR
Liu, CT
Nalls, MA
Rundek, T
Sacco, RL
Smith, J
Sun, YV
Wilson, G
Zhang, ZG
Mosley, TH
Taylor, HA
Vasan, RS
AF Musani, Solomon K.
Fox, Ervin R.
Kraja, Aldi
Bidulescu, Aurelian
Lieb, Wolfgang
Lin, Honghuang
Beecham, Ashley
Chen, Ming-Huei
Felix, Janine F.
Fox, Caroline S.
Kao, W. H. Linda
Kardia, Sharon L. R.
Liu, Ching-Ti
Nalls, Mike A.
Rundek, Tatjana
Sacco, Ralph L.
Smith, Jennifer
Sun, Yan V.
Wilson, Gregory
Zhang, Zhaogong
Mosley, Thomas H.
Taylor, Herman A.
Vasan, Ramachandran S.
TI Genome-Wide Association Analysis of Plasma B-Type Natriuretic Peptide in
Blacks The Jackson Heart Study
SO CIRCULATION-CARDIOVASCULAR GENETICS
LA English
DT Article
DE genetic association studies; genetics; genome-wide association study;
genotype
ID STAGE RENAL-DISEASE; BLOOD-PRESSURE; ESSENTIAL-HYPERTENSION; BNP LEVELS;
GENE; COMMON; POLYMORPHISM; VARIANTS; FAILURE; RISK
AB Background-Numerous experimental studies suggest that B-type natriuretic peptide (BNP) is cardioprotective; however, in clinical studies, higher plasma BNP concentrations have been associated with incident cardiovascular disease and higher left ventricular mass. Genetic association studies may allow us to determine the true causal directions without confounding by compensatory mechanisms.
Methods and Results-We performed a meta-analysis of 2 genome-wide association results from a total of 2790 blacks. We assumed an additive genetic model in an association analysis of imputed 2.5 million single-nucleotide polymorphism dosages with residuals generated from multivariable-adjusted logarithmically transformed BNP controlling for relevant covariates and population stratification. Two loci were genome-wide significant, a candidate gene locus NPPB (rs198389, P=1.18x10(-09)) and a novel missense variant in the KLKB1 locus (rs3733402, P=1.75x10(-11)) that explained 0.4% and 1.9% of variation in log BNP concentration, respectively. The observed increase in BNP concentration was proportional to the number of effect allele copies, and an average of 8.1 pg/mL increase was associated with 2 allele copies. In a companion study, single-nucleotide polymorphisms in this loci were cross-checked with genome-wide association results for the aldosterone/renin ratio in individuals of European ancestry, and rs3733402 was genome-wide significant (P<5.0x10(-8)), suggesting possible shared genetic architecture for these 2 pathways. Other statistically significant relations for these single-nucleotide polymorphisms included the following: rs198389 with systolic blood pressure in blacks (COGENT consortium) and rs198389 and rs3733402 with left ventricular mass in whites (EchoGEN consortium).
Conclusions-These findings improve our knowledge of the genetic basis of BNP variation in blacks, demonstrate a possible shared allelic architecture for BNP with aldosterone-renin ratio, and motivate further studies of underlying mechanisms.
C1 [Musani, Solomon K.; Mosley, Thomas H.] Univ Mississippi, Med Ctr, Dept Med, Jackson, MS 39213 USA.
[Fox, Ervin R.] Univ Mississippi, Med Ctr, Div Cardiol, Jackson, MS 39213 USA.
[Kraja, Aldi] Washington Univ, Sect Stat Genom, St Louis, MO 63130 USA.
[Bidulescu, Aurelian] Indiana Univ, Dept Epidemiol & Biostat, Bloomington, IN 47405 USA.
[Lieb, Wolfgang] Univ Kiel, Kiel, Germany.
[Lieb, Wolfgang; Felix, Janine F.; Fox, Caroline S.; Vasan, Ramachandran S.] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Lin, Honghuang] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA.
Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA.
[Vasan, Ramachandran S.] Boston Univ, Sch Med, Dept Med, Sect Prevent Med, Boston, MA 02118 USA.
[Vasan, Ramachandran S.] Boston Univ, Sch Med, Dept Med, Cardiol Sect, Boston, MA 02118 USA.
[Vasan, Ramachandran S.] Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Boston, MA 02118 USA.
[Sacco, Ralph L.] Univ Miami, Dept Neurol, Coral Gables, FL 33124 USA.
Univ Miami, John P Hussman Inst Human Genom, Miller Sch Med, Coral Gables, FL 33124 USA.
[Rundek, Tatjana] Univ Miami, Dept Publ Hlth Serv, Coral Gables, FL 33124 USA.
[Beecham, Ashley; Sacco, Ralph L.] Univ Miami, Coral Gables, FL 33124 USA.
[Felix, Janine F.] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.
[Felix, Janine F.] Netherlands Consortium Hlth Aging NGI NCHA, Genom Initiat, Leiden, Netherlands.
[Kao, W. H. Linda] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Kardia, Sharon L. R.; Smith, Jennifer] Univ Michigan, Dept Epidemiol, Ann Arbor, MI 48109 USA.
[Liu, Ching-Ti] Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA.
[Nalls, Mike A.] NIA, Mol Genet Sect, Bethesda, MD 20892 USA.
[Sun, Yan V.] Emory Univ, Dept Epidemiol, Atlanta, GA 30322 USA.
[Wilson, Gregory] Jackson State Univ, Coll Publ Serv, Jackson, MS USA.
[Zhang, Zhaogong] Case Western Reserve Univ, Sch Med, Dept Epidemiol & Biostat, Cleveland, OH 44106 USA.
Morehouse Sch Med, Cardiovasc Res Ctr, Atlanta, GA 30310 USA.
RP Musani, SK (reprint author), Univ Mississippi, Med Ctr, 350 W Woodrow Wilson Ave,Suite 701, Jackson, MS 39213 USA.
EM smusani@umc.edu
RI Lieb, Wolfgang/C-1990-2012;
OI Felix, Janine/0000-0002-9801-5774; Lin, Honghuang/0000-0003-3043-3942;
Ramachandran, Vasan/0000-0001-7357-5970; Smith,
Jennifer/0000-0002-3575-5468
FU National Heart, Lung, and Blood Institute on Minority Health and Health
Disparities [HSN268201300046C, HHSN268201300047C, HHSN268201300048C,
HHSN268201300049C, HHSN268201300050C]
FX The Jackson Heart Study is supported by contracts HSN268201300046C,
HHSN268201300047C, HHSN268201300048C, HHSN268201300049C, and
HHSN268201300050C from the National Heart, Lung, and Blood Institute on
Minority Health and Health Disparities.
NR 46
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U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1942-325X
EI 1942-3268
J9 CIRC-CARDIOVASC GENE
JI Circ.-Cardiovasc. Genet.
PD FEB
PY 2015
VL 8
IS 1
BP 122
EP 130
DI 10.1161/CIRCGENETICS.114.000900
PG 9
WC Cardiac & Cardiovascular Systems; Genetics & Heredity
SC Cardiovascular System & Cardiology; Genetics & Heredity
GA CB8IW
UT WOS:000349873200017
PM 25561047
ER
PT J
AU Gronholm, J
Lenardo, MJ
AF Groenholm, Juha
Lenardo, Michael J.
TI Novel diagnostic and therapeutic approaches for autoimmune diabetes - A
prime time to treat insulitis as a disease
SO CLINICAL IMMUNOLOGY
LA English
DT Review
DE Autoantibody; Insulitis; Type 1 diabetes; Tolerance
ID RANDOMIZED CONTROLLED-TRIAL; HEAT-SHOCK-PROTEIN; BETA-CELL FUNCTION;
ANTIBODY STANDARDIZATION PROGRAM; GLUTAMIC-ACID DECARBOXYLASE;
RECENT-ONSET; DOUBLE-BLIND; 1ST-DEGREE RELATIVES; GENERAL-POPULATION;
COXSACKIEVIRUS B1
AB Type 1 diabetes is a progressive autoimmune disease with no curative treatment, making prevention critical. At the time of diagnosis, a majority of the insulin secreting beta-cells have already been destroyed. Insulitis, lymphocytic infiltration to the pancreatic islets, is believed to begin months to years before the clinical symptoms of insulin deficiency appear. Insulitis should be treated as its own disease, for it is a known precursor to autoimmune diabetes. Because it is difficult to detect insulitic cellular infiltrates noninvasively, considerable interest has been focused on the levels of islet autoantibodies in blood as measurable diagnostic markers for islet autoimmunity. The traditional islet autoantibody detection assays have many limitations. New electrochemiluminescence-based autoantibody detection assays have the potential to overcome these challenges and they offer promising, cost-effective screening tools in identifying high-risk individuals for trials of preventive interventions. Here, we outline diagnostic and therapeutic strategies to overcome pancreatic beta-cell destroying insulitis. (C) 2014 Elsevier Inc. All rights reserved.
C1 [Groenholm, Juha; Lenardo, Michael J.] NIAID, Mol Dev Immune Syst Sect, Immunol Lab, Clin Genom Program,NIH, Bethesda, MD 20892 USA.
RP Lenardo, MJ (reprint author), NIAID, Mol Dev Immune Syst Sect, Immunol Lab, Clin Genom Program,NIH, Bldg 10,Room 11D14,Ctr Dr, Bethesda, MD 20892 USA.
EM juhapetrikristian.gronholm@nih.gov; lenardo@nih.gov
FU Division of Intramural Research, National Institute of Allergy and
Infectious Diseases; Clinical Center; National Human Genome Research
Institute, National Institutes of Health; Sigrid Juselius Foundation;
Emil Aaltonen Foundation
FX We thank Anthony Venida for the careful review of our manuscript as well
as Prof. David Harlan and Dr. Kimberly Shafer-Weaver on their valuable
comments on the manuscript. Dr. Samuli Rounioja is acknowledged for
providing us the IAA-RIA protocol. This research was supported by the
Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, Clinical Center, and National Human Genome Research
Institute, National Institutes of Health. J.G. was supported by a
fellowship grant from Sigrid Juselius Foundation and by Emil Aaltonen
Foundation. Wellstat Diagnostics LLC and Novo Nordisk are acknowledged
for their collaboration.
NR 87
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U1 1
U2 11
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1521-6616
EI 1521-7035
J9 CLIN IMMUNOL
JI Clin. Immunol.
PD FEB
PY 2015
VL 156
IS 2
BP 109
EP 118
DI 10.1016/j.clim.2014.11.007
PG 10
WC Immunology
SC Immunology
GA CC2QL
UT WOS:000350189600003
PM 25486604
ER
PT J
AU McCully, CML
Bacher, J
MacAllister, RP
Steffen-Smith, EA
Saleem, K
Thomas, ML
Cruz, R
Warren, KE
AF McCully, Cynthia M. Lester
Bacher, John
MacAllister, Rhonda P.
Steffen-Smith, Emilie A.
Saleem, Kadharbatcha
Thomas, Marvin L., III
Cruz, Rafael
Warren, Katherine E.
TI Development of a Cerebrospinal Fluid Lateral Reservoir Model in Rhesus
Monkeys (Macaca mulatta)
SO COMPARATIVE MEDICINE
LA English
DT Article
ID DRUGS
AB Rapid, serial, and humane collection of cerebrospinal fluid (CSF) in nonhuman primates (NHP) is an essential element of numerous research studies and is currently accomplished via two different models. The CSF reservoir model (FR) combines a catheter in the 4th ventricle with a flexible silastic reservoir to permit circulating CSF flow. The CSF lateral port model (LP) consists of a lateral ventricular catheter and an IV port that provides static access to CSF and volume restrictions on sample collection. The FR model is associated with an intensive, prolonged recovery and frequent postsurgical hydrocephalus and nonpatency, whereas the LP model is associated with an easier recovery. To maximize the advantages of both systems, we developed the CSF lateral reservoir model (LR), which combines the beneficial features of the 2 previous models but avoids their limitations by using a reservoir for circulating CSF flow combined with catheter placement in the lateral ventricle. Nine adult male rhesus monkeys were utilized in this study. Pre-surgical MRI was performed to determine the coordinates of the lateral ventricle and location of choroid plexus (CP). The coordinates were determined to avoid the CP and major blood vessels. The predetermined coordinates were 100% accurate, according to MRI validation. The LR system functioned successfully in 67% of cases for 221 d, and 44% remain functional at 426 to 510 d postoperatively. Compared with established models, our LR model markedly reduced postoperative complications and recovery time. Development of the LR model was successful in rhesus macaques and is a useful alternative to the FR and LP methods of CSF collection from nonhuman primates.
C1 [McCully, Cynthia M. Lester; MacAllister, Rhonda P.; Steffen-Smith, Emilie A.; Cruz, Rafael; Warren, Katherine E.] NCI, Bethesda, MD 20892 USA.
[Bacher, John; Thomas, Marvin L., III] Off Res Serv, Bethesda, MD USA.
[Saleem, Kadharbatcha] NIMH, Bethesda, MD 20892 USA.
RP McCully, CML (reprint author), NCI, Bethesda, MD 20892 USA.
EM mccullyc@mail.nih.gov
NR 6
TC 1
Z9 1
U1 1
U2 2
PU AMER ASSOC LABORATORY ANIMAL SCIENCE
PI MEMPHIS
PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA
SN 1532-0820
J9 COMPARATIVE MED
JI Comparative Med.
PD FEB
PY 2015
VL 65
IS 1
BP 77
EP 82
PG 6
WC Veterinary Sciences; Zoology
SC Veterinary Sciences; Zoology
GA CC0FD
UT WOS:000350010300010
ER
PT J
AU Ashish, N
Bamman, MM
Cerny, FJ
Cooper, DM
D'Hemecourt, P
Eisenmann, JC
Ericson, D
Fahey, J
Falk, B
Gabriel, D
Kahn, MG
Kemper, HCG
Leu, SY
Liem, RI
McMurray, R
Nixon, PA
Olin, JT
Pianosi, PT
Purucker, M
Radom-Aizik, S
Taylor, A
AF Ashish, Naveen
Bamman, Marcas M.
Cerny, Frank J.
Cooper, Dan M.
D'Hemecourt, Pierre
Eisenmann, Joey C.
Ericson, Dawn
Fahey, John
Falk, Bareket
Gabriel, Davera
Kahn, Michael G.
Kemper, Han C. G.
Leu, Szu-Yun
Liem, Robert I.
McMurray, Robert
Nixon, Patricia A.
Olin, J. Tod
Pianosi, Paolo T.
Purucker, Mary
Radom-Aizik, Shlomit
Taylor, Amy
TI The Clinical Translation Gap in Child Health Exercise Research: A Call
for Disruptive Innovation
SO CTS-CLINICAL AND TRANSLATIONAL SCIENCE
LA English
DT Article
DE exercise; clinical trials; pediatrics; data harmonization;
cardiopulmonary exercise testing
ID MAXIMAL OXYGEN-UPTAKE; PHYSICAL-ACTIVITY; AEROBIC FITNESS; ADOLESCENTS;
DISEASE; ASTHMA; OBESITY; YOUTH; VO2
AB In children, levels of play, physical activity, and fitness are key indicators of health and disease and closely tied to optimal growth and development. Cardiopulmonary exercise testing (CPET) provides clinicians with biomarkers of disease and effectiveness of therapy, and researchers with novel insights into fundamental biological mechanisms reflecting an integrated physiological response that is hidden when the child is at rest. Yet the growth of clinical trials utilizing CPET in pediatrics remains stunted despite the current emphasis on preventative medicine and the growing recognition that therapies used in children should be clinically tested in children. There exists a translational gap between basic discovery and clinical application in this essential component of child health. To address this gap, the NIH provided funding through the Clinical and Translational Science Award (CTSA) program to convene a panel of experts. This report summarizes our major findings and outlines next steps necessary to enhance child health exercise medicine translational research. We present specific plans to bolster data interoperability, improve child health CPET reference values, stimulate formal training in exercise medicine for child health care professionals, and outline innovative approaches through which exercise medicine can become more accessible and advance therapeutics across the broad spectrum of child health.
C1 [Ashish, Naveen] Univ So Calif, Dept Neurol, Los Angeles, CA 90089 USA.
[Bamman, Marcas M.] Univ Alabama Birmingham, Dept Cell Dev & Integrat Biol, Birmingham, AL USA.
[Cerny, Frank J.] SUNY Buffalo, Dept Pediat, Womens & Childrens Hosp Buffalo, Buffalo, NY USA.
[Cooper, Dan M.; Leu, Szu-Yun; Radom-Aizik, Shlomit] Univ Calif Irvine, Inst Clin & Translat Sci, Dept Pediat, Pediat Exercise & Genom Res Ctr, Irvine, CA 92697 USA.
[D'Hemecourt, Pierre] Boston Childrens Hosp, Div Sports Med, Boston, MA USA.
[Eisenmann, Joey C.] Michigan State Univ, Coll Osteopath Med, E Lansing, MI 48824 USA.
[Ericson, Dawn] Boston Childrens Hosp, Dept Pulm Med, Boston, MA USA.
[Fahey, John] Yale Univ, New Haven, CT USA.
[Falk, Bareket] Brock Univ, Dept Kinesiol, St Catharines, ON L2S, Canada.
[Gabriel, Davera] Univ Calif Davis, Ctr Hlth Technol, Davis, CA 95616 USA.
[Kahn, Michael G.] Univ Colorado, Dept Pediat, Aurora, CO USA.
[Kemper, Han C. G.] Vrije Univ Amsterdam Med Ctr, EMGO Inst, Amsterdam, Netherlands.
[Liem, Robert I.] Northwestern Univ Feinberg Sch Med, Div Pediat Hematol, Chicago, IL USA.
[McMurray, Robert] Univ N Carolina, Dept Exercise & Sport Sci, Chapel Hill, NC USA.
[Nixon, Patricia A.] Wake Forest Univ, Dept Hlth & Exercise Sci, Winston Salem, NC 27109 USA.
[Olin, J. Tod] Natl Jewish Hlth, Dept Pediat, Denver, CO USA.
[Pianosi, Paolo T.] Mayo Clin, Dept Pediat & Adolescent Med, Rochester, MN USA.
[Purucker, Mary] NIH, Natl Ctr Adv Translat Sci, Bethesda, MD 20892 USA.
[Taylor, Amy] Childrens Hosp Colorado, Childrens Clin Res Org & Pediat Cardiol, Aurora, CO USA.
RP Cooper, DM (reprint author), Univ Calif Irvine, Inst Clin & Translat Sci, Dept Pediat, Pediat Exercise & Genom Res Ctr, Irvine, CA 92697 USA.
EM dcooper@uci.edu
FU NIH through the Clinical and Translational Science Award (CTSA) at the
University of California, Irvine [3UL1RR031985]; Mechanisms of Health
Effects of Exercise in Children [P01HD-048721]
FX This effort was supported by NIH through the Clinical and Translational
Science Award (CTSA) at the University of California, Irvine (Grant
3UL1RR031985) and a program project grant, Mechanisms of Health Effects
of Exercise in Children (P01HD-048721). The contents of this paper are
solely the responsibility of the authors and do not necessarily
represent the official views of the National Center for Advancing
Translational Sciences or the National Institutes of Health.
NR 52
TC 4
Z9 5
U1 2
U2 21
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1752-8054
EI 1752-8062
J9 CTS-CLIN TRANSL SCI
JI CTS-Clin. Transl. Sci.
PD FEB
PY 2015
VL 8
IS 1
BP 67
EP 76
DI 10.1111/cts.12194
PG 10
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA CC0BT
UT WOS:000350000700015
PM 25109386
ER
PT J
AU Nash, TE
Mahanty, S
Loeb, JA
Theodore, WH
Friedman, A
Sander, JW
Singh, G
Cavalheiro, E
Del Brutto, OH
Takayanagui, OM
Fleury, A
Verastegui, M
Preux, PM
Montano, S
Pretell, EJ
White, AC
Gonzales, AE
Gilman, RH
Garcia, HH
AF Nash, Theodore E.
Mahanty, Siddhartha
Loeb, Jeffrey A.
Theodore, William H.
Friedman, Alon
Sander, Josemir W.
Singh, Gagandeep
Cavalheiro, Esper
Del Brutto, Oscar H.
Takayanagui, Osvaldo M.
Fleury, Agnes
Verastegui, Manuela
Preux, Pierre-Marie
Montano, Silvia
Pretell, E. Javier
White, A. Clinton
Gonzales, Armando E.
Gilman, Robert H.
Garcia, Hector H.
TI Neurocysticercosis: A natural human model of epileptogenesis
SO EPILEPSIA
LA English
DT Article
DE Epilepsy; Seizure; Taenia solium; Helminth
ID TEMPORAL-LOBE EPILEPSY; TERM-FOLLOW-UP; CALCIFIED NEUROCYSTICERCOSIS;
PERILESIONAL EDEMA; HIPPOCAMPAL SCLEROSIS; CALCIFICATIONS; ASSOCIATION
AB ObjectiveTo develop a better understanding of mechanisms of seizures and long-term epileptogenesis using neurocysticercosis.
MethodsA workshop was held bringing together experts in epilepsy and epileptogenesis and neurocysticercosis.
ResultsHuman neurocysticercosis and parallel animal models offer a unique opportunity to understand basic mechanisms of seizures. Inflammatory responses to degenerating forms and later-stage calcified parasite granulomas are associated with seizures and epilepsy. Other mechanisms may also be involved in epileptogenesis.
SignificanceNaturally occurring brain infections with neurocysticercosis offer a unique opportunity to develop treatments for one of the world's most common causes of epilepsy and for the development of more general antiepileptogenic treatments. Key advantages stem from the time course in which an acute seizure heralds a start of the epileptogenic process, and radiographic changes of calcification and perilesional edema provide biomarkers of a chronic epileptic state.
C1 [Nash, Theodore E.; Mahanty, Siddhartha] Natl Inst Allergy & Infect Dis, Natl Inst Hlth, Parasit Dis Lab, Bethesda, MD USA.
[Loeb, Jeffrey A.] Univ Illinois, Dept Neurol & Rehabil, Chicago, IL USA.
[Theodore, William H.] Natl Inst Neurol Disorders & Stroke, Natl Inst Hlth, Epilepsy Sect, Bethesda, MD USA.
[Friedman, Alon] Ben Gurion Univ Negev, Zlotowski Ctr Neuroscience, Negev, Beer Sheva, Israel.
[Friedman, Alon] Dalhousie Univ, Dept Med Neuroscience, Halifax, NS, Canada.
[Sander, Josemir W.] UCL Inst Neurol, NIHR UCL Hosp Biomed Res Ctr, Dept Clin Expt Epilepsy, London, United Kingdom.
[Sander, Josemir W.] Netherlands Fdn, Epilepsy Inst, Heemstede, Netherlands.
[Singh, Gagandeep] Dept Neurol, Dayan & Med Coll, Ludhiana, Punjab, India.
[Cavalheiro, Esper] Univ Fed Sao Paulo, Dept Neurol & Neurosurgery, Sao Paulo, Brazil.
[Del Brutto, Oscar H.] Univ Espiritu Santo, Sch Med, Guayaquil, Ecuador.
[Takayanagui, Osvaldo M.] RibeirAo Preto Med Sch Univ SAo Paulo, Dept Neurosciences & Behav, Ribeirao Preto, Brazil.
[Fleury, Agnes] Natl Autonomous Univ Mexico & Natl Inst Neurol &, Inst Biomed Res, Mexico City, DF, Mexico.
[Verastegui, Manuela] Univ Peruana Cayetano Heredia, Fac Sci & Philosophy, Dept Cellular & Mol Sci, Lima, Peru.
[Preux, Pierre-Marie] Univ Limoges, Inst Neuroepidemiol & Trop Neurol, INSERM, CHU Limoges, Limoges, France.
[Montano, Silvia] US Naval Med Res Unit 6, Callao, Peru.
[Pretell, E. Javier] Hosp Alberto Sabogal, Dept Neurol, Callao, Peru.
[White, A. Clinton] Univ Texas, Div Infect Dis, Dept Internal Med, Galveston, TX USA.
[Gonzales, Armando E.] Natl Univ San Marcos, Sch Vet Med, Dept Vet Publ Hlth, Lima, Peru.
[Gilman, Robert H.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Int Hlth, Baltimore, MD USA.
[Garcia, Hector H.] Inst Neurol Dis, Cysticercosis Unit, Lima, Peru.
[Garcia, Hector H.] Univ Peruana Cayetano Heredia, Univ Peruana Cayetano Heredia, Dept Microbiol, Ctr Global Hlth Tumbes, Lima, Peru.
RP Nash, TE (reprint author), 9000 Rockville Pike,Bldg 4, Bethesda, MD 20892 USA.
EM tnash@niaid.nih.gov
RI Sander, Josemir/C-1576-2008; PREUX, Pierre-Marie/B-8393-2014;
Takayanagui, Osvaldo/C-8159-2013;
OI Sander, Josemir/0000-0001-6041-9661; PREUX,
Pierre-Marie/0000-0002-2171-2977; Takayanagui,
Osvaldo/0000-0002-8190-0275; White, A Clinton/0000-0002-9668-4632;
Mahanty, Siddhartha/0000-0003-1068-0524
FU Intramural Research Program of the National Institute of Allergy and
Infectious Diseases from the National Institutes of Health; Office of
Rare Diseases Research from the National Institutes of Health; National
Center for Advancing Translational Sciences from the National Institutes
of Health; Fogarty International Center Training Grant from the National
Institutes of Health [D43 TW00114]; Wellcome Trust Senior International
Research Fellowship in Tropical Medicine and Public Health
FX Supported in part by the Intramural Research Program of the National
Institute of Allergy and Infectious Diseases, the Office of Rare
Diseases Research, the National Center for Advancing Translational
Sciences, and Fogarty International Center Training Grant D43 TW00114,
all from the National Institutes of Health. H.G. is supported by a
Wellcome Trust Senior International Research Fellowship in Tropical
Medicine and Public Health.
NR 29
TC 11
Z9 11
U1 2
U2 14
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0013-9580
EI 1528-1167
J9 EPILEPSIA
JI Epilepsia
PD FEB
PY 2015
VL 56
IS 2
BP 177
EP 183
DI 10.1111/epi.12849
PG 7
WC Clinical Neurology
SC Neurosciences & Neurology
GA CC2AH
UT WOS:000350146300013
PM 25534640
ER
PT J
AU Welch, RD
Nicholas, K
Durkalski-Mauldin, VL
Lowenstein, DH
Conwit, R
Mahajan, PV
Lewandowski, C
Silbergleit, R
AF Welch, Robert D.
Nicholas, Katherine
Durkalski-Mauldin, Valerie L.
Lowenstein, Daniel H.
Conwit, Robin
Mahajan, Prashant V.
Lewandowski, Christopher
Silbergleit, Robert
CA Neurological Emergencies Treatment
TI Intramuscular midazolam versus intravenous lorazepam for the prehospital
treatment of status epilepticus in the pediatric population
SO EPILEPSIA
LA English
DT Article
DE Status epilepticus; Prehospital treatment; Pediatrics
ID RANDOMIZED CLINICAL-TRIAL; DIAZEPAM; CHILDREN; RESUSCITATION;
MANAGEMENT; SEIZURES; ADULTS
AB ObjectiveTo examine the effectiveness of intramuscular (IM) midazolam versus intravenous (IV) lorazepam for the treatment of pediatric patients with status epilepticus (SE) in the prehospital care setting.
MethodsThis multicenter clinical trial randomized patients diagnosed with SE to receive either IM midazolam or IV lorazepam administered by paramedics in the prehospital care setting. Included in this secondary analysis were only patients younger than 18years of age. Evaluated were the associations of the treatment group (IM vs. IV) with the primary outcome, defined as seizure cessation prior to emergency department (ED) arrival, and with patient characteristics, time to important events, and adverse events. Descriptive statistics and 99% confidence intervals (CIs) were used for the analysis.
ResultsOf 893 primary study subjects, 120 met criteria for this study (60 in each treatment group). There were no differences in important baseline characteristics or seizure etiologies between groups. The primary outcome was met in 41 (68.3%) and 43 (71.7%) of subjects in the IM and IV groups, respectively (risk difference [RD] -3.3%, 99% CI -24.9% to 18.2%). Similar results were noted for those younger than 11years (RD -1.3%, 99% CI -25.7% to 23.1%). Time from initiating the treatment protocol was shorter for children who received IM midazolam, mainly due to the shorter time to administer the active treatment. Safety profiles were similar.
SignificanceIM midazolam can be rapidly administered and appears to be safe and effective for the management of children with SE treated in the prehospital setting. The results must be interpreted in the context of the secondary analysis design and sample size of the study.
C1 [Welch, Robert D.] Wayne State Univ Sch Med, Dept Emergency Med, Detroit, MI USA.
[Welch, Robert D.] Wayne State Univ Sch Med, Cardiovasc Res Inst, Detroit, MI USA.
[Nicholas, Katherine; Durkalski-Mauldin, Valerie L.] Med Univ S Carolina, Dept Publ Hlth Sci, Charleston, SC 29425 USA.
[Lowenstein, Daniel H.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA.
[Conwit, Robin] NINDS, NIH, Bethesda, MD 20892 USA.
[Mahajan, Prashant V.] Wayne State Univ Sch Med, Dept Pediat, Detroit, MI USA.
[Lewandowski, Christopher] Henry Ford Hlth Syst, Dept Emergency Med, Detroit, MI USA.
[Silbergleit, Robert] Univ Michigan, Dept Emergency Med, Ann Arbor, MI 48109 USA.
RP Welch, RD (reprint author), Wayne State Univ Sch Med, Detroit Receiving Hosp UHC 6G, Dept Emergency Med, 4201 St Antoine, Detroit, MI 48201 USA.
EM rwelch@med.wayne.edu
FU National Institute of Neurological Disorders and Stroke (NINDS)
[U01NS056975, U01NS059041]; National Institutes of Health Office of the
Director CounterACT Program
FX Grant Support: National Institute of Neurological Disorders and Stroke
(NINDS) (U01NS056975 and U01NS059041); National Institutes of Health
Office of the Director CounterACT Program; Biomedical Advanced Research
and Development Authority of the Assistant Secretary for Preparedness
and Response.
NR 15
TC 11
Z9 11
U1 0
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0013-9580
EI 1528-1167
J9 EPILEPSIA
JI Epilepsia
PD FEB
PY 2015
VL 56
IS 2
BP 254
EP 262
DI 10.1111/epi.12905
PG 9
WC Clinical Neurology
SC Neurosciences & Neurology
GA CC2AH
UT WOS:000350146300023
PM 25597369
ER
PT J
AU Yi, F
DeCan, E
Stoll, K
Marceau, E
Deisseroth, K
Lawrence, JJ
AF Yi, Feng
DeCan, Evan
Stoll, Kurt
Marceau, Eric
Deisseroth, Karl
Lawrence, J. Josh
TI Muscarinic excitation of parvalbumin-positive interneurons contributes
to the severity of pilocarpine-induced seizures
SO EPILEPSIA
LA English
DT Article
DE Pilocarpine; Muscarinic; Acetylcholine; Hippocampus; Seizures
ID TEMPORAL-LOBE EPILEPSY; PROTEIN-COUPLED RECEPTORS; GAMMA OSCILLATIONS;
CHOLINERGIC MODULATION; MOUSE HIPPOCAMPUS; PYRAMIDAL CELLS; M1 RECEPTOR;
IN-VITRO; MODEL; MICE
AB ObjectiveA common rodent model in epilepsy research employs the muscarinic acetylcholine receptor (mAChR) agonist pilocarpine, yet the mechanisms underlying the induction of pilocarpine-induced seizures (PISs) remain unclear. Global M-1 mAChR (M1R) knockout mice are resistant to PISs, implying that M1R activation disrupts excitation/inhibition balance. Parvalbumin-positive (PV) inhibitory neurons express M(1)Rs, participate in cholinergically induced oscillations, and can enter a state of depolarization block (DB) during epileptiform activity. Here, we test the hypothesis that pilocarpine activation of M(1)Rs expressed on PV cells contributes to PISs.
MethodsCA1 PV cells in PV-CRE mice were visualized with a floxed YFP or hM3Dq-mCherry adeno-associated virus, or by crossing PV-CRE mice with the RosaYFP reporter line. To eliminate M(1)Rs from PV cells, we generated PV-M(1)knockout (KO) mice by crossing PV-CRE and floxed M-1 mice. Action potential (AP) frequency was monitored during application of pilocarpine (200m). In behavioral experiments, locomotion and seizure symptoms were recorded in wild-type (WT) or PV-M1KO mice during PISs.
ResultsPilocarpine significantly increased AP frequency in CA1 PV cells into the gamma range. In the continued presence of pilocarpine, a subset (5/7) of PV cells progressed to DB, which was mimicked by hM3Dq activation of Gq-receptor signaling. Pilocarpine-induced depolarization, AP firing at gamma frequency, and progression to DB were prevented in CA1 PV cells of PV-M1KO mice. Finally, compared to WT mice, PV-M1KO mice were associated with reduced severity of PISs.
SignificancePilocarpine can directly depolarize PV+ cells via M1R activation, but a subset of these cells progress to DB. Our electrophysiologic and behavioral results suggest that this mechanism is active during PISs, contributing to a collapse of PV-mediated -aminobutyric acid (GABA)ergic inhibition, dysregulation of excitation/inhibition balance, and increased susceptibility to PISs.
C1 [Yi, Feng; DeCan, Evan; Stoll, Kurt; Marceau, Eric; Lawrence, J. Josh] Univ Montana, COBRE Ctr Struct & Funct Neurosci, Missoula, MT 59812 USA.
[Yi, Feng; DeCan, Evan; Stoll, Kurt; Marceau, Eric; Lawrence, J. Josh] Univ Montana, Dept Biomed & Pharmaceut Sci, Missoula, MT 59812 USA.
[DeCan, Evan] Univ Montana, Davidson Honors Coll, Missoula, MT 59812 USA.
[Deisseroth, Karl] Stanford Univ, Dept Bioengn, Stanford, CA 94305 USA.
RP Lawrence, JJ (reprint author), Univ Montana, Dept Biomed & Pharmaceut Sci, COBRE Ctr Struct & Funct Neurosci, 391 Skaggs Bldg,32 Campus Dr, Missoula, MT 59812 USA.
EM josh.lawrence@umontana.edu
FU National Institutes of Health (NIH) [R01 NS069689]; NCRR [P20RR015583];
Epilepsy Foundation; Davidson Honors College Undergraduate Research
Award; NSF National Science Foundation Experimental Program to Stimulate
Competitive Research (EPSCoR); University of Montana Small Grants
Program; Montana State University Mountains and Minds Research
Experiences for Undergraduates Program [NSF REU 1156855]; National
Center for Research Resources [P20RR015583, P20RR017670, P20GM10356]
FX We thank Drs. Susumu Tonegawa and David Gerber (MIT) for floxed
M1 mice, Ed Calloway (Salk Institute) and Silvia Arber
(University of Basel, Switzerland) for PV-CRE mice, Dr. Bryan Roth
(University of North Carolina-Chapel Hill) for hM3Dq-mCherry AAV, Miriam
Rose Baker for preliminary data on PIS experiments, Alison Hixon for
help with genotyping, and Drs. Laura Ewell, Debbie Smith, and Neil
Nathanson for critically reviewing the manuscript. Funding was from the
National Institutes of Health (NIH) R01 NS069689 (JJL), NCRR P20RR015583
(JJL), the Epilepsy Foundation (JJL), a Davidson Honors College
Undergraduate Research Award (ED), NSF National Science Foundation
Experimental Program to Stimulate Competitive Research (EPSCoR) (KES),
the University of Montana Small Grants Program (JJL and KES), and the
Montana State University Mountains and Minds Research Experiences for
Undergraduates Program (NSF REU 1156855; EM). ED was a Center for
Structural and Functional Neuroscience Summer Undergraduate Research
Fellow. National Center for Research Resources P20RR015583, P20RR017670,
and P20GM10356 grants supported core imaging and behavioral facilities.
NR 55
TC 8
Z9 8
U1 1
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0013-9580
EI 1528-1167
J9 EPILEPSIA
JI Epilepsia
PD FEB
PY 2015
VL 56
IS 2
BP 297
EP 309
DI 10.1111/epi.12883
PG 13
WC Clinical Neurology
SC Neurosciences & Neurology
GA CC2AH
UT WOS:000350146300028
PM 25495999
ER
PT J
AU Kirsch, M
Mitchell, SA
Dobbels, F
Stussi, G
Basch, E
Halter, JP
De Geest, S
AF Kirsch, Monika
Mitchell, Sandra A.
Dobbels, Fabienne
Stussi, Georg
Basch, Ethan
Halter, Jorg P.
De Geest, Sabina
TI Linguistic and content validation of a German-language PRO-CIVAE-based
patient-reported outcomes instrument to evaluate the late effect symptom
experience after allogeneic hematopoietic stem cell transplantation
SO EUROPEAN JOURNAL OF ONCOLOGY NURSING
LA English
DT Article
DE Patient-reported outcomes; Stem cell transplantation; PRO-CTCAE;
Survivorship; Late effects; Validity; Mixed methods; Symptom experience
ID QUALITY-OF-LIFE; VERSUS-HOST-DISEASE; TASK-FORCE REPORT; CONSENSUS
DEVELOPMENT PROJECT; BONE-MARROW-TRANSPLANTATION; WORKING GROUP-REPORT;
LONG-TERM SURVIVORS; CLINICAL-TRIALS; CANCER-PATIENTS; CARE
AB Purpose: The aim of this sequential mixed methods study was to develop a PRO-CTCAE (Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events)-based measure of the symptom experience of late effects in German speaking long-term survivors of allogeneic stem cell transplantation (SCT), and to examine its content validity.
Methods: The US National Cancer Institute's PRO-CTAE item library was translated into German and linguistically validated. PRO-CTCAE symptoms prevalent in >50% of survivors (n = 15) and recognized in its importance by SCT experts (n = 9) were identified. Additional concepts relevant to the symptom experience and its consequences were elicited. Content validity of the PROVIVO (Patient-Reported Outcomes of long-term survivors after allogeneic SCT) instrument was assessed through an additional round of cognitive debriefing in 15 patients, and item and scale content validity indices by 9 experts.
Results: PROVIVO is comprised of a total of 49 items capturing the experience of physical, emotional and cognitive symptoms. To improve the instrument's utility for clinical decision-making, questions soliciting limitations in activities of daily living, frequent infections, and overall well-being were added. Cognitive debriefings demonstrated that items were well understood and relevant to the SCT survivor experience. Scale Content Validity Index (CVI) (0.94) and item CVI (median = 1; range 0.75-1) were very high.
Conclusions: Qualitative and quantitative data provide preliminary evidence supporting the content validity of PROVIVO and identify a PRO-CTCAE item bundle for use in SCT survivors. A study to evaluate the measurement properties of PROVIVO and to examine its capacity to improve survivorship care planning is underway. (C) 2014 Elsevier Ltd. All rights reserved.
C1 [Kirsch, Monika; De Geest, Sabina] Univ Basel, Inst Nursing Sci, CH-4056 Basel, Switzerland.
[Kirsch, Monika; Halter, Jorg P.] Univ Basel Hosp, Dept Haematol, Basel, Switzerland.
[Mitchell, Sandra A.] NCI, Div Canc Control & Populat Sci, Outcomes Res Branch, Bethesda, MD 20892 USA.
[Dobbels, Fabienne; De Geest, Sabina] Katholieke Univ Leuven, Dept Publ Hlth & Primary Care, Hlth Serv & Nursing Res, Leuven, Belgium.
[Stussi, Georg] Oncol Inst Southern Switzerland, Dept Haematol, Bellinzona, Switzerland.
[Basch, Ethan] Univ N Carolina, Lineberger Comprehens Canc Ctr, Canc Outcomes Res Program, Chapel Hill, NC 27515 USA.
RP De Geest, S (reprint author), Univ Basel, Inst Nursing Sci, Bernoullistr 28, CH-4056 Basel, Switzerland.
EM sabina.degeest@unibas.ch
FU Foundation Cancer Research Switzerland [KFS 2705-08-2010]; Stiftung zur
Krebsbekampfung [2010/280]
FX This study was supported by grants from the Foundation Cancer Research
Switzerland (KFS 2705-08-2010) and the 'Stiftung zur Krebsbekampfung'
(2010/280).
NR 38
TC 4
Z9 4
U1 3
U2 6
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1462-3889
EI 1532-2122
J9 EUR J ONCOL NURS
JI Eur. J. Oncol. Nurs.
PD FEB
PY 2015
VL 19
IS 1
BP 66
EP 74
DI 10.1016/j.ejon.2014.07.007
PG 9
WC Oncology; Nursing
SC Oncology; Nursing
GA CC1AW
UT WOS:000350074400012
PM 25190633
ER
PT J
AU Gu, J
Lei, Y
Huang, YP
Zhao, YY
Li, J
Huang, T
Zhang, JJ
Wang, JP
Deng, XD
Chen, ZS
Korteweg, C
Deng, RS
Yan, ML
Xu, Q
Dong, SN
Cai, MH
Luo, LL
Huang, GW
Wang, Y
Li, Q
Lin, CM
Su, M
Yang, CZ
Zhuang, ZP
AF Gu, Jiang
Lei, Yu
Huang, Yuanping
Zhao, Yingying
Li, Jing
Huang, Tao
Zhang, Junjun
Wang, Juping
Deng, Xiaodong
Chen, Zhengshan
Korteweg, Christine
Deng, Ruishu
Yan, Meiling
Xu, Qian
Dong, Shengnan
Cai, Monghong
Luo, Lili
Huang, Guowei
Wang, Yun
Li, Qian
Lin, Changmei
Su, Meng
Yang, Chunzhang
Zhuang, Zhengping
TI Fab fragment glycosylated IgG may play a central role in placental
immune evasion
SO HUMAN REPRODUCTION
LA English
DT Article
DE asymmetric immunoglobulin G; placenta; immune evasion; leukocyte; fetus
ID IMMUNOGLOBULIN-G EXPRESSION; NEWLY SYNTHESIZED PROTEINS;
CANCER-CELL-LINES; ASYMMETRIC ANTIBODIES; CHORIONIC VILLI; FC-RECEPTORS;
PREGNANCY; TRANSMISSION; NEURONS; BINDING
AB STUDY QUESTION: How does the placenta protect the fetus from immune rejection by the mother?
SUMMARY ANSWER: The placenta can produce IgG that is glycosylated at one of its Fab arms (asymmetric IgG; aIgG) which can interact with other antibodies and certain leukocytes to affect local immune reactions at the junction between the two genetically distinct entities.
WHAT IS KNOWN ALREADY: The placenta can protect the semi-allogenic fetus from immune rejection by the immune potent mother. aIgG in serum is increased during pregnancy and returns to the normal range after giving birth. aIgG can react to antigens to form immune complexes which do not cause a subsequent immune effector reaction, including fixing complements, inducing cytotoxicity and phagocytosis, and therefore has been called 'blocking antibody'.
STUDY DESIGN, SIZE, DURATION: Eighty-eight human placentas, four trophoblast cell lines (TEV-1, JAR, JEG and BeWo), primary culture of human placental trophoblasts and a gene knock-out mouse model were investigated in this study.
PARTICIPANTS/MATERIALS, SETTING, METHODS: The general approach included the techniques of cell culture, immunohistochemistry, in situ hybridization, immuno-electron microscopy, western blot, quantitative PCR, protein isolation, glycosylation analysis, enzyme digestion, gene sequencing, mass spectrophotometry, laser-guided microdissection, enzyme-linked immunosorbent assay, pulse chase assay, double and multiple staining to analyze protein and DNA and RNA analysis at the cellular and molecular levels.
MAIN RESULTS AND THE ROLE OF CHANCE: Three major discoveries were made: (i) placental trophoblasts and endothelial cells are capable of producing IgG, a significant portion of which is aberrantly glycosylated at one of its Fab arms to form aIgG; (ii) the asymmetrically glycosylated IgG produced by trophoblasts and endothelial cells can react to immunoglobulin molecules of human, rat, mouse, goat and rabbit at the Fc portion; (iii) asymmetrically glycosylated IgG can react to certain leukocytes in the membrane and cytoplasm, while symmetric IgG from the placenta does not have this property.
LIMITATIONS, REASONS FOR CAUTION: Most of the experiments were performed in vitro. The proposed mechanism calls for verification in normal and abnormal pregnancy.
WIDER IMPLICATIONS OF THE FINDINGS: This study identified a number of new phenomena suggesting that aIgG produced by the placenta would be able to react to detrimental antibodies and leukocytes and interfere with their immune reactions against the placenta and the fetus. This opens a new dimension for further studies on pregnancy physiology and immunology. Should the mechanism proposed here be confirmed, it will have a direct impact on our understanding of the physiology and pathology of human reproduction and offer new possibilities for the treatment of many diseases including spontaneous abortion, infertility and pre-eclampsia. It also sheds light on the mechanism of immune evasion in general including that of cancer.
C1 [Gu, Jiang; Lei, Yu; Huang, Yuanping; Zhao, Yingying; Li, Jing; Huang, Tao; Zhang, Junjun; Wang, Juping; Deng, Xiaodong; Chen, Zhengshan; Korteweg, Christine; Deng, Ruishu; Yan, Meiling; Xu, Qian; Dong, Shengnan; Huang, Guowei; Wang, Yun; Li, Qian; Su, Meng] Shantou Univ Med Coll, Dept Pathol, Shantou 515041, Guangdong, Peoples R China.
[Gu, Jiang; Lei, Yu; Huang, Yuanping; Zhao, Yingying; Li, Jing; Huang, Tao; Zhang, Junjun; Wang, Juping; Deng, Xiaodong; Chen, Zhengshan; Korteweg, Christine; Deng, Ruishu; Yan, Meiling; Xu, Qian; Dong, Shengnan; Huang, Guowei; Wang, Yun; Li, Qian; Su, Meng] Shantou Univ Med Coll, Prov Key Lab Infect Dis & Immunopathol, Shantou 515041, Guangdong, Peoples R China.
[Gu, Jiang; Zhao, Yingying; Deng, Ruishu; Su, Meng] Beijing Univ Hlth Sci Ctr, Dept Pathol, Beijing 100083, Peoples R China.
[Gu, Jiang; Cai, Monghong] Shantou Univ Med Coll, Affiliated Hosp 2, Translat Med Ctr, Shantou, Peoples R China.
[Luo, Lili] Shantou Univ Med Coll, Affiliated Hosp 1, Dept Gynecol & Obstetrician, Shantou, Peoples R China.
[Lin, Changmei] Haidian Maternal & Child Hlth Hosp, Dept Fertil, Beijing 100080, Peoples R China.
[Yang, Chunzhang; Zhuang, Zhengping] NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA.
RP Gu, J (reprint author), Shantou Univ Med Coll, Dept Pathol & Pathophysiol, Shantou, Peoples R China.
EM 2523381625@qq.com
FU National Nature Science Foundation of China [30971150, 81030033]; Li
KaShing Foundation
FX This work was supported by grants from the National Nature Science
Foundation of China (No. 30971150 and 81030033 to J.G.) and The Li
KaShing Foundation.
NR 50
TC 6
Z9 6
U1 2
U2 15
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0268-1161
EI 1460-2350
J9 HUM REPROD
JI Hum. Reprod.
PD FEB
PY 2015
VL 30
IS 2
BP 380
EP 391
DI 10.1093/humrep/deu323
PG 12
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA CC2AK
UT WOS:000350146600016
PM 25505012
ER
PT J
AU Eisenberg, ML
Kim, S
Chen, Z
Sundaram, R
Schisterman, EF
Louis, GMB
AF Eisenberg, Michael L.
Kim, Sungduk
Chen, Zhen
Sundaram, Rajeshwari
Schisterman, Enrique F.
Louis, Germaine M. Buck
TI The relationship between male BMI and waist circumference on semen
quality: data from the LIFE study (vol 29, pg 193, 2014)
SO HUMAN REPRODUCTION
LA English
DT Correction
C1 [Eisenberg, Michael L.] Stanford Univ, Sch Med, Dept Urol, Stanford, CA 94305 USA.
[Eisenberg, Michael L.] Stanford Univ, Sch Med, Dept Obstet, Stanford, CA 94305 USA.
[Eisenberg, Michael L.] Stanford Univ, Sch Med, Dept Gynecol, Stanford, CA 94305 USA.
[Kim, Sungduk; Chen, Zhen; Sundaram, Rajeshwari; Schisterman, Enrique F.; Louis, Germaine M. Buck] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, Rockville, MD 20852 USA.
RP Eisenberg, ML (reprint author), Stanford Univ, Sch Med, Dept Urol, 300 Pasteur Dr, Stanford, CA 94305 USA.
EM eisenberg@stanford.edu
OI Eisenberg, Michael/0000-0001-5482-0141
NR 2
TC 0
Z9 3
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0268-1161
EI 1460-2350
J9 HUM REPROD
JI Hum. Reprod.
PD FEB
PY 2015
VL 30
IS 2
BP 493
EP 494
DI 10.1093/humrep/deu322
PG 2
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA CC2AK
UT WOS:000350146600031
PM 25516559
ER
PT J
AU Spieker, EA
Sbrocco, T
Theim, KR
Maurer, D
Johnson, D
Bryant, E
Bakalar, JL
Schvey, NA
Ress, R
Seehusen, D
Klein, DA
Stice, E
Yanovski, JA
Chan, L
Gentry, S
Ellsworth, C
Hill, JW
Tanofsky-Kraff, M
Stephens, MB
AF Spieker, Elena A.
Sbrocco, Tracy
Theim, Kelly R.
Maurer, Douglas
Johnson, Dawn
Bryant, Edny
Bakalar, Jennifer L.
Schvey, Natasha A.
Ress, Rachel
Seehusen, Dean
Klein, David A.
Stice, Eric
Yanovski, Jack A.
Chan, Linda
Gentry, Shari
Ellsworth, Carol
Hill, Joanne W.
Tanofsky-Kraff, Marian
Stephens, Mark B.
TI Preventing Obesity in the Military Community (POMC): The Development of
a Clinical Trials Research Network
SO INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH
LA English
DT Article
ID RANDOMIZED EFFICACY TRIAL; EATING-DISORDER; ADULT OBESITY; INTERPERSONAL
PSYCHOTHERAPY; DESERT-STORM; HIGH-RISK; METABOLIC SYNDROME; ADOLESCENT
GIRLS; WEIGHT-GAIN; BODY-WEIGHT
AB Obesity impacts the U.S. military by affecting the health and readiness of active duty service members and their families. Preventing Obesity in Military Communities (POMC) is a comprehensive research program within Patient Centered Medical Homes (PCMHs) in three Military Training Facilities. This paper describes three pilot randomized controlled trials that target critical high risk periods for unhealthy weight gain from birth to young adulthood: (1) pregnancy and early infancy (POMC-Mother-Baby), (2) adolescence (POMC-Adolescent), and (3) the first tour of duty after boot camp (POMC-Early Career). Each study employs a two-group randomized treatment or prevention program with follow up. POMC offers a unique opportunity to bring together research and clinical expertise in obesity prevention to develop state-of-the-art programs within PCMHs in Military Training Facilities. This research builds on existing infrastructure that is expected to have immediate clinical benefits to DoD and far-reaching potential for ongoing collaborative work. POMC may offer an economical approach for widespread obesity prevention, from conception to young adulthood, in the U.S. military as well as in civilian communities.
C1 [Spieker, Elena A.; Maurer, Douglas] Madigan Army Med Ctr, Dept Family Med, Tacoma, WA 98431 USA.
[Spieker, Elena A.; Sbrocco, Tracy; Theim, Kelly R.; Johnson, Dawn; Bryant, Edny; Bakalar, Jennifer L.; Schvey, Natasha A.; Ress, Rachel; Tanofsky-Kraff, Marian] Uniformed Serv Univ Hlth Sci, Dept Med & Clin Psychol, Bethesda, MD 20814 USA.
[Spieker, Elena A.; Theim, Kelly R.; Bakalar, Jennifer L.; Schvey, Natasha A.; Ress, Rachel] Henry M Jackson Fdn Adv Mil Med Inc, Bethesda, MD 20817 USA.
[Seehusen, Dean] Dept Family & Community Med, Ft Gordon, GA 30905 USA.
[Klein, David A.] Ft Belvoir Community Hosp, Dept Family Med, Ft Belvoir, VA 22060 USA.
[Stice, Eric] Oregon Res Inst, Eugene, OR 97403 USA.
[Yanovski, Jack A.; Tanofsky-Kraff, Marian] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Growth & Obes, Program Dev Endocrinol & Genet, NIH,DHHS, Bethesda, MD 20892 USA.
[Chan, Linda] Naval Hosp Camp Lejeune, Dept Obstet & Gynecol, Camp Lejeune, NC 28547 USA.
[Gentry, Shari; Ellsworth, Carol] Naval Hosp Camp Lejeune, Dept Family Med, Camp Lejeune, NC 28547 USA.
[Hill, Joanne W.] Naval Hosp Camp Lejeune, Dept Res, Camp Lejeune, NC 28547 USA.
[Stephens, Mark B.] Uniformed Serv Univ Hlth Sci, Dept Family Med, Bethesda, MD 20814 USA.
RP Sbrocco, T (reprint author), Uniformed Serv Univ Hlth Sci, Dept Med & Clin Psychol, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA.
EM elena.a.spieker.ctr@mail.mil; tracy.sbrocco@usuhs.edu;
kelly.theim.ctr@usuhs.edu; douglas.m.maurer.mil@mail.mil;
dawn.johnson@usuhs.edu; edny.joseph@usuhs.edu;
Jennifer.bakalar@usuhs.edu; natasha.schvey.ctr@usuhs.edu;
rachel.ress.ctr@usuhs.edu; Dean.A.Seehusen.mil@health.mil;
david.a.klein26.mil@mail.mil; estice@ori.org; yanovskj@mail.nih.gov;
Linda.Chan@med.navy.mil; shari.gentry@med.navy.mil;
carol.ellsworth@med.navy.mil; Joanne.Hill@med.navy.mil;
marian.tanofsky-kraff@usuhs.edu; mark.stephens@usuhs.edu
OI Yanovski, Jack/0000-0001-8542-1637
FU Uniformed Services University [USUHS72NC-01]; NICHD [Z1aHD00641];
[F172NC-02]
FX Research support provided by a grant from the Uniformed Services
University (USUHS72NC-01) to Tracy Sbrocco and intramural support from
NICHD (Z1aHD00641) to Jack A. Yanovski, a Commissioned Officer in the
United States Public Health Service. This manuscript was developed
within the scope of work for the Henry M. Jackson Foundation for the
Advancement of Military Medicine, Inc., by authors Elena A. Spieker,
Kelly R. Theim supported by grant F172NC-02.
NR 57
TC 3
Z9 3
U1 3
U2 6
PU MDPI AG
PI BASEL
PA POSTFACH, CH-4005 BASEL, SWITZERLAND
SN 1660-4601
J9 INT J ENV RES PUB HE
JI Int. J. Environ. Res. Public Health
PD FEB
PY 2015
VL 12
IS 2
BP 1174
EP 1195
DI 10.3390/ijerph120201174
PG 22
WC Environmental Sciences; Public, Environmental & Occupational Health
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health
GA CC2XZ
UT WOS:000350209800008
PM 25648176
ER
PT J
AU Phelan, S
Kanaya, AM
Ma, Y
Vittinghoff, E
Barrett-Connor, E
Wing, R
Kusek, JW
Orchard, TJ
Crandall, JP
Montez, MG
Brown, JS
AF Phelan, Suzanne
Kanaya, Alka M.
Ma, Yong
Vittinghoff, Eric
Barrett-Connor, Elizabeth
Wing, Rena
Kusek, John W.
Orchard, Trevor J.
Crandall, Jill P.
Montez, Maria G.
Brown, Jeanette S.
CA Diabet Prevention Program Res Grp
TI Long-term prevalence and predictors of urinary incontinence among women
in the Diabetes Prevention Program Outcomes Study
SO INTERNATIONAL JOURNAL OF UROLOGY
LA English
DT Article
DE Diabetes Prevention Program Outcomes Study; lifestyle intervention;
urinary incontinence; weight loss
ID LIFE-STYLE INTERVENTION; WEIGHT-LOSS; EPIDEMIOLOGIC SURVEY; EXERCISE;
RISK; CLASSIFICATION; POPULATION; REMISSION; MELLITUS; STRESS
AB ObjectivesTo examine the long-term prevalence and predictors of weekly urinary incontinence in the Diabetes Prevention Program Outcomes Study, a follow-up study of the Diabetes Prevention Program randomized clinical trial of overweight adults with impaired glucose tolerance.
MethodsThis analysis included 1778 female participants of the Diabetes Prevention Program Outcomes Study who had been randomly assigned during the Diabetes Prevention Program to intensive lifestyle intervention (n=582), metformin (n=589) or placebo (n=607). The study participants completed semi-annual assessments after the final Diabetes Prevention Program visit and for 6years until October 2008.
ResultsAt the study entry, the prevalence of weekly urinary incontinence was lower in the intensive lifestyle intervention group compared with the metformin and placebo groups (44.2% vs 51.8%, 48.0% urinary incontinence/week, P=0.04); during the 6-year follow-up period, these lower rates in intensive lifestyle intervention were maintained (46.7%, 53.1%, 49.9% urinary incontinence/week; P=0.03). Statistically adjusting for urinary incontinence prevalence at the end of the Diabetes Prevention Program, the treatment arm no longer had a significant impact on urinary incontinence during the Diabetes Prevention Program Outcomes Study. Independent predictors of lower urinary incontinence during the Diabetes Prevention Program Outcomes Study included lower body mass index (odds ratio 0.988, 95% confidence interval 0.982-0.994) and greater physical activity (odds ratio 0.999, 95% confidence interval 0.998-1.000) at the Diabetes Prevention Program Outcomes Study entry, and greater reductions in body mass index (odds ratio 0.75, 95% confidence interval 0.60-0.94) and waist circumference (odds ratio 0.998, 95% confidence interval 0.996-1.0) during the Diabetes Prevention Program Outcomes Study. Diabetes was not significantly related to urinary incontinence.
ConclusionsIntensive lifestyle intervention has a modest positive and enduring impact on urinary incontinence, and should be considered for the long-term prevention and treatment of urinary incontinence in overweight/obese women with glucose intolerance.
C1 [Phelan, Suzanne] Calif Polytech State Univ San Luis Obispo, Kinesiol Dept, San Luis Obispo, CA 93407 USA.
[Kanaya, Alka M.] Univ Calif San Francisco, Dept Gen Internal Med, San Francisco, CA 94143 USA.
[Ma, Yong] George Washington Univ, Biostat Ctr, Rockville, MD 20852 USA.
[Vittinghoff, Eric] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
[Barrett-Connor, Elizabeth] Univ Calif San Diego, Div Epidemiol, San Diego, CA 92103 USA.
[Wing, Rena] Brown Univ, Warren Alpert Med Sch, Dept Psychiat & Human Behav, Providence, RI 02912 USA.
[Wing, Rena] Miriam Hosp, Providence, RI 02906 USA.
[Kusek, John W.] NIDDK, Div Kidney Urol & Hematol Dis, Bethesda, MD 20892 USA.
[Orchard, Trevor J.] Univ Pittsburgh, Pittsburgh, PA USA.
[Crandall, Jill P.] Albert Einstein Coll Med, Bronx, NY 10467 USA.
[Montez, Maria G.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA.
[Brown, Jeanette S.] UCSF Womens Hlth Clin Res Ctr, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA USA.
[Brown, Jeanette S.] UCSF Womens Hlth Clin Res Ctr, Dept Urol, San Francisco, CA USA.
[Brown, Jeanette S.] UCSF Womens Hlth Clin Res Ctr, Dept Epidemiol, San Francisco, CA USA.
RP Phelan, S (reprint author), George Washington Univ, Biostat Ctr, 6110 Execut Blvd,Suite 750, Rockville, MD 20852 USA.
EM dppmail@biostat.bsc.gwu.edu
OI orchard, trevor/0000-0001-9552-3215
FU National Institute of Diabetes and Digestive and Kidney Diseases
(NIDDK); National Institute of Diabetes and Digestive and Kidney
Diseases of the National Institutes of Health; Southwestern American
Indian Centers; National Institute of Child Health and Human
Development; National Institute on Aging; National Eye Institute, the
National Heart Lung and Blood Institute; Office of Women's Health;
National Center for Minority Health and Human Disease; Centers for
Disease Control and Prevention; American Diabetes Association
FX This study was funded by the National Institute of Diabetes and
Digestive and Kidney Diseases (NIDDK) as a cooperative agreement. We
thank the participants of the Diabetes Prevention Program and Diabetes
Prevention Program Outcomes Study for their commitment and dedication;
the National Institute of Diabetes and Digestive and Kidney Diseases of
the National Institutes of Health for funding to the clinical and
coordinating centers that designed and undertook the study, and
collected, managed, analyzed and interpreted the data; and the General
Clinical Research Center Program and the National Center for Research
Resources for support of data collection at many of the clinical
centers. The Southwestern American Indian Centers were supported
directly by the National Institute of Diabetes and Digestive and Kidney
Diseases, including its Intramural Research Program, and by the Indian
Health Service. Funding was also provided by the National Institute of
Child Health and Human Development, the National Institute on Aging, the
National Eye Institute, the National Heart Lung and Blood Institute, the
Office of Women's Health, the National Center for Minority Health and
Human Disease, the Centers for Disease Control and Prevention, and the
American Diabetes Association. Lipha (Merck-Sante) provided medicines,
and LifeScan donated materials. The opinions expressed are those of the
investigators, and do not necessarily reflect the views of the funding
agencies. Comments by three anonymous reviewers are gratefully
acknowledged.
NR 37
TC 1
Z9 1
U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0919-8172
EI 1442-2042
J9 INT J UROL
JI Int. J. Urol.
PD FEB
PY 2015
VL 22
IS 2
BP 206
EP 212
DI 10.1111/iju.12654
PG 7
WC Urology & Nephrology
SC Urology & Nephrology
GA CB9TU
UT WOS:000349976800021
PM 25352018
ER
PT J
AU Takeshita, J
Wang, SW
Shin, DB
Mehta, NN
Kimmel, SE
Margolis, DJ
Troxel, AB
Gelfand, JM
AF Takeshita, Junko
Wang, Shuwei
Shin, Daniel B.
Mehta, Nehal N.
Kimmel, Stephen E.
Margolis, David J.
Troxel, Andrea B.
Gelfand, Joel M.
TI Effect of Psoriasis Severity on Hypertension Control A Population-Based
Study in the United Kingdom
SO JAMA DERMATOLOGY
LA English
DT Article
ID II-INDUCED HYPERTENSION; ANGIOTENSIN-II; CARDIOVASCULAR-DISEASE;
MYOCARDIAL-INFARCTION; RISK-FACTORS; VASCULAR DYSFUNCTION;
BLOOD-PRESSURE; METAANALYSIS; PREVALENCE; COMORBIDITIES
AB IMPORTANCE Hypertension is prevalent among patients with psoriasis. The effect of psoriasis and its severity on hypertension control is unknown.
OBJECTIVE To determine the association between uncontrolled blood pressure and psoriasis, both overall and according to objectively measured psoriasis severity, among patients with diagnosed hypertension.
DESIGN, SETTING, AND PARTICIPANTS Population-based cross-sectional study nested in a prospective cohort drawn from The Health Improvement Network (THIN), an electronic medical records database broadly representative of the general population in the United Kingdom. The study population included a random sample of patients with psoriasis (n = 1322) between the ages of 25 and 64 years in THIN who were included in the Incident Health Outcomes and Psoriasis Events prospective cohort and their age-and practice-matched controls without psoriasis (n = 11 977). All included patients had a diagnosis of hypertension; their psoriasis diagnosis was confirmed and disease severity was classified by their general practitioners.
MAIN OUTCOMES AND MEASURES Uncontrolled hypertensionwas defined as a systolic blood pressure of 140mmHg or higher or a diastolic blood pressure of 90mmHg or higher based on the blood pressure recorded closest in time to the assessment of psoriasis severity.
RESULTS There was a significant positive dose-response relationship between uncontrolled hypertension and psoriasis severity as objectively determined by the affected body surface area in both unadjusted and adjusted analyses that controlled for age, sex, body mass index, smoking and alcohol use status, presence of comorbid conditions, and current use of antihypertensive medications and nonsteroidal anti-inflammatory drugs (adjusted odds ratio [aOR], 0.97; 95% CI, 0.82-1.14 for mild psoriasis; aOR, 1.20; 95% CI, 0.99-1.45 for moderate psoriasis; and aOR, 1.48; 95% CI, 1.08-2.04 for severe psoriasis; P =.01 for trend). The likelihood of uncontrolled hypertension among psoriasis overall was also increased, although not statistically significantly so (aOR, 1.10; 95% CI, 0.98-1.24).
CONCLUSIONS AND RELEVANCE Among patients with hypertension, psoriasiswas associated with a greater likelihood of uncontrolled hypertension in a dose-dependent manner, with the greatest likelihood observed among those with moderate to severe psoriasis defined by 3% or more of the body surface area affected. Our data suggest a need for more effective
C1 [Takeshita, Junko; Shin, Daniel B.; Margolis, David J.; Gelfand, Joel M.] Univ Penn, Perelman Sch Med, Dept Dermatol, Philadelphia, PA 19104 USA.
[Takeshita, Junko; Shin, Daniel B.; Kimmel, Stephen E.; Margolis, David J.; Troxel, Andrea B.; Gelfand, Joel M.] Univ Penn, Perelman Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA USA.
[Wang, Shuwei] Thomas Jefferson Univ, Div Internal Med, Philadelphia, PA 19107 USA.
[Mehta, Nehal N.] NHLBI, Sect Inflammat & Cardiometab Dis, Bethesda, MD 20892 USA.
[Kimmel, Stephen E.] Univ Penn, Perelman Sch Med, Div Cardiol, Philadelphia, PA USA.
RP Takeshita, J (reprint author), Univ Penn, Perelman Sch Med, Dept Dermatol, 1463 Penn Tower,One Convent Ave, Philadelphia, PA 19104 USA.
EM junko.takeshita@uphs.upenn.edu
OI Troxel, Andrea/0000-0002-1393-3075
FU National Heart, Lung, and Blood Institute [RO1-HLO89744]; National
Institute of Arthritis and Musculoskeletal and Skin Diseases
[K24-ARO6431O]; Dermatology Foundation Career Development Award;
National Psoriasis Foundation Fellowship Award
FX This study was supported by grant RO1-HLO89744 from the National Heart,
Lung, and Blood Institute (Dr Gelfand), grant K24-ARO6431O from the
National Institute of Arthritis and Musculoskeletal and Skin Diseases
(Dr Gelfand), a Dermatology Foundation Career Development Award (Dr
Takeshita), and a National Psoriasis Foundation Fellowship Award (Dr
Takeshita).
NR 46
TC 11
Z9 11
U1 0
U2 1
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 2168-6068
EI 2168-6084
J9 JAMA DERMATOL
JI JAMA Dermatol.
PD FEB
PY 2015
VL 151
IS 2
BP 161
EP 169
DI 10.1001/jamadermatol.2014.2094
PG 9
WC Dermatology
SC Dermatology
GA CB6RL
UT WOS:000349754200010
PM 25322196
ER
PT J
AU Zuo, RC
Apolo, AB
DiGiovanna, JJ
Parnes, HL
Keen, CM
Nanda, S
Dahut, WL
Cowen, EW
AF Zuo, Rena C.
Apolo, Andrea B.
DiGiovanna, John J.
Parnes, Howard L.
Keen, Corrine M.
Nanda, Swati
Dahut, William L.
Cowen, Edward W.
TI Cutaneous Adverse Effects Associated With the Tyrosine-Kinase Inhibitor
Cabozantinib
SO JAMA DERMATOLOGY
LA English
DT Article
ID FOOT SKIN REACTION; PALMAR-PLANTAR ERYTHRODYSESTHESIA; MESYLATE CAUSES
HYPOPIGMENTATION; SUBUNGUAL SPLINTER HEMORRHAGES; MEDULLARY-THYROID
CANCER; RENAL-CELL CARCINOMA; PROSTATE-CANCER; VITAMIN-E; SUNITINIB;
SORAFENIB
AB IMPORTANCE Cabozantinib S-malate is a vascular endothelial growth factor receptor 2, c-MET, and RET multitargeted tyrosine kinase inhibitor that has antiangiogenic and antitumorigenic properties with potential efficacy for the treatment of several cancers. Cutaneous reactions, one of the most frequently observed adverse effects associated with tyrosine kinase inhibitors, can significantly affect patients' quality of life and drug adherence and represent a major therapeutic challenge to maximizing the efficacy of targeted cancer therapy.
OBJECTIVE To describe the frequency and spectrum of skin reactions in patients with urothelial carcinoma receiving cabozantinib as monotherapy.
DESIGN, SETTING, AND PARTICIPANTS A single-institution study at the Clinical Research Center at the National Institutes of Health included 41 consecutive adults with metastatic, progressive urothelial carcinoma enrolled in a National Cancer Institute open-label, nonrandomized, phase 2 clinical trial. Patients receiving cabozantinib were evaluated for the development of skin reactions at each treatment visit from October 2012 to June 2014 by the primary oncology team and referred for dermatologic evaluation as appropriate.
MAIN OUTCOMES AND MEASURES A detailed history, full-body physical examination, and clinical photographs of cutaneous lesions were obtained.
RESULTS Of 41 consecutive patients who received cabozantinib, 30 (73%) developed 1 or more cutaneous toxic effects. Adverse events included hand-foot skin reaction (22 [54%]), generalized pigment dilution and/or hair depigmentation (18 [44%]), xerosis (8 [20%]), scrotal erythema/ulceration (6 [15%]), and nail splinter hemorrhages (5 [12%]). Eighteen patients (44%) had 2 or more cutaneous adverse events. Reactions developed in 17 of 30 patients (57%) during the first month of cabozantinib treatment and in 24 of 30 (80%) by the second month. Of patients with skin toxic effects, dose reduction was required for symptom management in 9 of 30 patients (30%), and treatment discontinuation was required in 4 of 30 (13%).
CONCLUSIONS AND RELEVANCE Cabozantinib monotherapy is associated with 1 or more cutaneous adverse events in most patients. Early detection and prompt treatment may increase patients' adherence to tyrosine kinase inhibitor therapy.
C1 [Zuo, Rena C.; DiGiovanna, John J.; Cowen, Edward W.] NCI, Dermatol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Apolo, Andrea B.; Keen, Corrine M.; Nanda, Swati; Dahut, William L.] NCI, Genitourinary Malignancies Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Parnes, Howard L.] NCI, Prostate & Urol Canc Res Grp, Canc Prevent Div, NIH, Bethesda, MD 20892 USA.
RP Cowen, EW (reprint author), NCI, Dermatol Branch, Ctr Canc Res, NIH, 10 Ctr Dr,MSC 1908,Bldg 10,Room 12N238, Bethesda, MD 20892 USA.
EM cowene@mail.nih.gov
FU Intramural Research Program of the National Institutes of Health (NIH);
National Cancer Institute; Medical Research Scholars Program; NIH;
Pfizer Inc; Doris Duke Charitable Foundation; Alexandria Real Estate
Equities, Inc; Howard Hughes Medical Institute
FX This research was supported by the Intramural Research Program of the
National Institutes of Health (NIH), National Cancer Institute, and the
Medical Research Scholars Program, a public-private partnership
supported jointly by the NIH and contributions to the Foundation for the
National Institutes of Health from Pfizer Inc, the Doris Duke Charitable
Foundation, the Alexandria Real Estate Equities, Inc, Mr and Mrs Joel S.
Marcus, and the Howard Hughes Medical Institute, as well as other
private donors.
NR 53
TC 4
Z9 4
U1 2
U2 7
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 2168-6068
EI 2168-6084
J9 JAMA DERMATOL
JI JAMA Dermatol.
PD FEB
PY 2015
VL 151
IS 2
BP 170
EP 177
DI 10.1001/jamadermatol.2014.2734
PG 8
WC Dermatology
SC Dermatology
GA CB6RL
UT WOS:000349754200012
PM 25427282
ER
PT J
AU Moraitis, AG
Freeman, LA
Shamburek, RD
Wesley, R
Wilson, W
Grant, CM
Price, S
Demosky, S
Thacker, SG
Zarzour, A
Hornung, RL
Pucino, F
Csako, G
Yarboro, C
McInnes, IB
Kuroiwa, T
Boumpas, D
Rao, VK
Illei, GG
Remaley, AT
AF Moraitis, Andreas G.
Freeman, Lita A.
Shamburek, Robert D.
Wesley, Robert
Wilson, Wyndham
Grant, Cliona M.
Price, Susan
Demosky, Stephen
Thacker, Seth G.
Zarzour, Abdalrahman
Hornung, Ronald L.
Pucino, Frank
Csako, Gyorgy
Yarboro, Cheryl
McInnes, Iain B.
Kuroiwa, Takashi
Boumpas, Dimitrios
Rao, V. Koneti
Illei, Gabor G.
Remaley, Alan T.
TI Elevated interleukin-10: A new cause of dyslipidemia leading to severe
HDL deficiency
SO JOURNAL OF CLINICAL LIPIDOLOGY
LA English
DT Article
DE "Disappearing HDL syndrome"; Severe HDL deficiency;
Hypertriglyceridemia; Dyslipidemia; B-cell lymphoma; Intravascular large
B-cell lymphoma; ALPS; Psoriasis; IL-10; LCAT
ID AUTOIMMUNE LYMPHOPROLIFERATIVE SYNDROME; LECITHIN-CHOLESTEROL
ACYLTRANSFERASE; DENSITY-LIPOPROTEIN-DEFICIENCY; INTESTINAL
EPITHELIAL-CELLS; FAS GENE-MUTATIONS; INHIBITS ATHEROSCLEROSIS; VISCERAL
LEISHMANIASIS; DISEASE; INFLAMMATION; LYMPHOMA
AB BACKGROUND: Low high-density lipoprotein cholesterol (HDL-C) is a risk factor for coronary artery disease. Investigating mechanisms underlying acquired severe HDL deficiency in noncritically ill patients ("disappearing EIDL syndrome") could provide new insights into HDL metabolism. OBJECTIVE: To determine the cause of low HDL-C in patients with severe acquired HDL deficiency.
METHODS AND RESULTS: Patients with intravascular large B-cell lymphoma (n = 2), diffuse large B-cell lymphoma (n = 1), and autoimmune lymphoproliferative syndrome (n = 1) presenting with markedly decreased EIDL-C, low low-density lipoprotein cholesterol (LDL-C), and elevated triglycerides were identified. The abnormal lipoprotein profile returned to normal after therapy in all 4 patients. All patients were found to have markedly elevated serum interleukin-10 (IL-10) levels that also normalized after therapy. In a cohort of autoimmune lymphoproliferative syndrome patients (n = 93), IL-10 showed a strong inverse correlation with HDL-C (R-2 = 0.3720, P < .0001). A direct causal role for increased serum IL-10 in inducing the observed changes in lipoproteins was established in a randomized, placebo-controlled clinical trial of recombinant human IL-10 in psoriatic arthritis patients (n = 18). Within a week of initiating subcutaneous recombinant human IL-10 injections, HDL-C precipitously decreased to near-undetectable levels. LDL-C also decreased by more than 50% (P < .0001) and triglycerides increased by approximately 2-fold (P < .005). All values returned to baseline after discontinuing IL-10 therapy.
CONCLUSION: Increased IL-10 causes severe HDL-C deficiency, low LDL-C, and elevated triglycerides. IL-10 is thus a potent modulator of lipoprotein levels, a potential new biomarker for B-cell disorders, and a novel cause of disappearing HDL syndrome. Published by Elsevier Inc. on behalf of National Lipid Association.
C1 [Moraitis, Andreas G.] Univ Michigan, Endocrine Oncol Program, Ann Arbor, MI 48109 USA.
[Freeman, Lita A.; Shamburek, Robert D.; Demosky, Stephen; Thacker, Seth G.; Zarzour, Abdalrahman; Remaley, Alan T.] NHLBI, Cardiovasc & Pulm Branch, NIH, Bethesda, MD 20892 USA.
[Wesley, Robert] NIH, Hosp Epidemiol, Bethesda, MD 20892 USA.
[Wilson, Wyndham; Grant, Cliona M.] NCI, NIH, Bethesda, MD 20892 USA.
[Price, Susan; Rao, V. Koneti] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA.
[Hornung, Ronald L.] Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Clin Serv Program, Frederick, MD USA.
[Pucino, Frank; Yarboro, Cheryl; McInnes, Iain B.; Kuroiwa, Takashi; Boumpas, Dimitrios; Illei, Gabor G.] NIAMSD, NIH, Bethesda, MD 20892 USA.
[Csako, Gyorgy; Remaley, Alan T.] NIH, Dept Lab Med, Bethesda, MD 20892 USA.
[McInnes, Iain B.] Univ Glasgow, Coll Med, Vet Med & Life Sci, Glasgow, Lanark, Scotland.
[Boumpas, Dimitrios] Univ Athens, Sch Med, GR-10679 Athens, Greece.
RP Remaley, AT (reprint author), NIH, Bldg 10,Rm 2C-433, Bethesda, MD 20892 USA.
EM aremaley1@cc.nih.gov
OI McInnes, Iain/0000-0002-6462-4280
FU National Cancer Institute, National Institutes of Health
[HHSN261200800001 E]; National Heart, Lung, and Blood Institute;
National Cancer Institute; National Institute of Allergy and Infectious
Diseases; National Institute of Arthritis and Musculoskeletal and Skin
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. HHSN261200800001 E and from intramural research funds from
the National Heart, Lung, and Blood Institute, National Cancer
Institute, National Institute of Allergy and Infectious Diseases and the
National Institute of Arthritis and Musculoskeletal and Skin Diseases.
The content of this publication does not necessarily reflect the views
or policies of the Department of Health and Human Services, nor does
mention of trade names, commercial products, or organizations imply
endorsement by the US. Government.
NR 52
TC 10
Z9 10
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1933-2874
EI 1876-4789
J9 J CLIN LIPIDOL
JI J. Clin. Lipidol.
PD FEB
PY 2015
VL 9
IS 1
BP 81
EP 90
DI 10.1016/j.jacl.2014.09.014
PG 10
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA CC1IB
UT WOS:000350093300012
PM 25670364
ER
PT J
AU Abramson, K
Keefe, B
Chou, WYS
AF Abramson, Karley
Keefe, Brian
Chou, Wen-Ying Sylvia
TI Communicating About Cancer Through Facebook: A Qualitative Analysis of a
Breast Cancer Awareness Page
SO JOURNAL OF HEALTH COMMUNICATION
LA English
DT Article
AB Social media channels are increasingly being used for health communication and promotion. Social networking sites such as Facebook have become popular platforms for organizations to communicate health messages and encourage user participation around health topics. While the evaluation of social media's effectiveness in health promotion is beginning to emerge in the literature, few studies have examined actual interactions and user behaviors on Facebook Pages hosted by health organizations. The authors present a qualitative case study of a popular Facebook Page from a nonprofit organization devoted to raising awareness about breast cancer. With the goal of identifying the functions and uses of the Page, our study analyzes the content of Wall posts during Breast Cancer Awareness Month, October 2010. Common themes and characteristics are identified, including open mic communication, scarcity of health information, the commodification of breast cancer, unpredictable locations of conversation, and the use of gendered images and language. The findings have potential implications for health promotion efforts using social media platforms.
C1 [Abramson, Karley] Univ Michigan, Sch Law, Ann Arbor, MI 48109 USA.
[Keefe, Brian] ICF Int, Rockville, MD 20850 USA.
[Chou, Wen-Ying Sylvia] NCI, Behav Res Program, Rockville, MD USA.
RP Keefe, B (reprint author), ICF Int, 530 Gaither Rd, Rockville, MD 20850 USA.
EM brian.keefe@icfi.com
NR 24
TC 5
Z9 6
U1 5
U2 23
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 1081-0730
EI 1087-0415
J9 J HEALTH COMMUN
JI J. Health Commun.
PD FEB 1
PY 2015
VL 20
IS 2
BP 237
EP 243
DI 10.1080/10810730.2014.927034
PG 7
WC Communication; Information Science & Library Science
SC Communication; Information Science & Library Science
GA CC4QS
UT WOS:000350338700014
PM 25495200
ER
PT J
AU Dauer, LT
Miller, DL
Schueler, B
Silberzweig, J
Balter, S
Bartal, G
Chambers, C
Collins, JD
Damilakis, J
Dixon, RG
Marx, MV
Stocker, MS
Vano, E
Venkatesan, AM
Nikolic, B
AF Dauer, Lawrence T.
Miller, Donald L.
Schueler, Beth
Silberzweig, James
Balter, Stephen
Bartal, Gabriel
Chambers, Charles
Collins, Jeremy D.
Damilakis, John
Dixon, Robert G.
Marx, M. Victoria
Stocker, Michael S.
Vano, Eliseo
Venkatesan, Aradhana M.
Nikolic, Boris
CA Soc Interventional Radiology Safet
Cardiovasc & Interventional Radiol
TI Occupational Radiation Protection of Pregnant or Potentially Pregnant
Workers in IR: A Joint Guideline of the Society of Interventional
Radiology and the Cardiovascular and Interventional Radiological Society
of Europe
SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY
LA English
DT Article
ID CARDIAC-CATHETERIZATION PROCEDURES; DIAGNOSTIC-RADIOLOGY; PROGRAM
GUIDELINES; WOMEN-RADIOLOGISTS; SAFETY PROGRAM; HEALTH HAZARDS;
EXPOSURE; PATIENT; CARDIOLOGY; STAFF
C1 [Dauer, Lawrence T.] Mem Sloan Kettering Canc Ctr, Dept Med Phys, New York, NY 10021 USA.
[Dauer, Lawrence T.] Mem Sloan Kettering Canc Ctr, Dept Radiol, New York, NY 10021 USA.
[Silberzweig, James] Beth Israel Deaconess Med Ctr, Dept Radiol, New York, NY 10003 USA.
[Balter, Stephen] Columbia Univ, Med Ctr, Dept Radiol, New York, NY 10003 USA.
[Balter, Stephen] Columbia Univ, Med Ctr, Dept Med, New York, NY 10003 USA.
[Nikolic, Boris] Stratton Med Ctr, Dept Radiol, Albany, NY USA.
[Miller, Donald L.] Food & Drug Adm, Ctr Devices & Radiol Hlth, Silver Spring, MD USA.
[Venkatesan, Aradhana M.] Natl Inst Hlth Clin Ctr, Bethesda, MD USA.
[Schueler, Beth] Mayo Clin, Dept Radiol, Rochester, MN USA.
[Chambers, Charles] Penn State Hershey Med Ctr, Penn State Hershey Heart & Vasc Inst, Hershey, PA USA.
[Collins, Jeremy D.] Northwestern Univ, Dept Radiol, Chicago, IL 60611 USA.
[Dixon, Robert G.] Univ N Carolina, Dept Radiol, Chapel Hill, NC USA.
[Marx, M. Victoria] Los Angeles Cty & Univ So Calif, Med Ctr, Dept Radiol, Los Angeles, CA USA.
[Stocker, Michael S.] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA.
[Bartal, Gabriel] Meir Med Ctr, Dept Diagnost & Intervent Radiol, Kefar Sava, Israel.
[Damilakis, John] Univ Crete, Fac Med, Dept Med Phys, Iraklion, Greece.
[Vano, Eliseo] Univ Complutense, Dept Radiol, E-28040 Madrid, Spain.
RP Dauer, LT (reprint author), SIR, 3975 Fair Ridge Dr,Suite 400 N, Fairfax, VA 22033 USA.
EM dauerl@mskcc.org
OI Dauer, Lawrence/0000-0002-5629-8462
NR 99
TC 2
Z9 2
U1 0
U2 5
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 FEB
PY 2015
VL 26
IS 2
BP 171
EP 181
DI 10.1016/j.jvir.2014.11.026
PG 11
WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular
Disease
SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System &
Cardiology
GA CB6MZ
UT WOS:000349742400004
PM 25645407
ER
PT J
AU Abi-Jaoudeh, N
Venkatesan, AM
Van der Sterren, W
Radaelli, A
Carelsen, B
Wood, BJ
AF Abi-Jaoudeh, Nadine
Venkatesan, Aradhana M.
Van der Sterren, William
Radaelli, Alessandro
Carelsen, Bart
Wood, Bradford J.
TI Clinical Experience with Cone-Beam CT Navigation for Tumor Ablation
SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY
LA English
DT Article
ID HEPATOCELLULAR-CARCINOMA; RADIOFREQUENCY ABLATION; PERCUTANEOUS
ABLATION; SURGICAL RESECTION; GUIDANCE; ACCURACY; FUSION; BIOPSY;
FEASIBILITY; FLUOROSCOPY
AB Purpose: To describe clinical use and potential benefits of cone-beam -computed tomography (CT) navigation to perform image-guided percutaneous tumor.ablation.
Materials and Methods: All ablations performed between February 2011 and February 2013 using cone-bearn CT navigation Were included. There Were 16 Patients who uriderWent 20 ablations for 29 lesions. Cone-beam. CT ablation planning Cap a bilities include multimodality image fusion and tumor segmentation for visualization, depiction of the predicted ablation zones for intraprocedural planning, and segmentation of the ablated area for immediate verification after treatment Number and purpose of cone-beam CT scans were, examined. The, initial ablation plan, defined as number of probes and duration of energy delivery, was recorded for the 26 of the 29 lesions ablated. Technical success and local recurrenCes were recotded: Primary and secondary effectiVeness rates were calculated.
Results: Image fusion was Used. for 16 lesions, and inttaprocedural ultrasound was used for 4 lesions. Of the 20 ablations, where the ablation plans Were recorded, there was no deviation from the plan in 14 ablations. In the remaining 6 ablations, iterative planning was needed for Coinplete tumot coverage. An. average of 8:7 cone-beam CT scans +/- 3.2 were performed per procedure, including 1.3 +/- 0.5 for tumot segmentation and planning, 1.7 +/- 0.7 for probe position confirmation, and 3.9 +/- 2 to ensure complete coverage. Mean follow-up time was 18,6, months +/- 6.5. Ablations for 28, of 29 lesions were technically successful (96.5%). Of ablations performed with curative intent, technical effectiveness at 1 month was 25 of 26, lesions (96.1%) and 22 of 26 lesions (84.6%) at last follow up Local tumor progression was observed in 11.5% (3 of 26 lesions).
Conclusions: Cone-beam CT navigation may add information to assist and improve ablation guidance and monitoring.
C1 [Abi-Jaoudeh, Nadine; Venkatesan, Aradhana M.; Wood, Bradford J.] NIH, Dept Radiol & Imaging Sci, Bethesda, MD 20892 USA.
[Van der Sterren, William; Radaelli, Alessandro; Carelsen, Bart] Philips Healthcare, iXR Div, Best, Netherlands.
RP Abi-Jaoudeh, N (reprint author), NIH, Dept Radiol & Imaging Sci, Room 1C365 Bldg 10 MSC 1182,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM naj@mail.nih.gov
FU National Institutes of Health Center for Interventional Oncology;
Intramural Research Program of the National Institutes of Health [ZID BC
011242-06]; National Institutes of Health; Philips Healthcare
FX This work was supported by the National Institutes of Health Center for
Interventional Oncology and the Intramural Research Program of the
National Institutes of Health (grant no. ZID BC 011242-06) and by a
collaborative research and development agreement between the National
Institutes of Health and Philips Healthcare.
NR 20
TC 5
Z9 5
U1 0
U2 1
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 FEB
PY 2015
VL 26
IS 2
BP 214
EP 219
DI 10.1016/j.jvir.2014.10.049
PG 6
WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular
Disease
SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System &
Cardiology
GA CB6MZ
UT WOS:000349742400011
PM 25645409
ER
PT J
AU Fragala, MS
Dam, TTL
Barber, V
Judge, JO
Studenski, SA
Cawthon, PM
McLean, RR
Harris, TB
Ferrucci, L
Guralnik, JM
Kiel, DP
Kritchevsky, SB
Shardell, MD
Vassileva, MT
Kenny, AM
AF Fragala, Maren S.
Dam, Thuy-Tien L.
Barber, Vanessa
Judge, James O.
Studenski, Stephanie A.
Cawthon, Peggy M.
McLean, Robert R.
Harris, Tamara B.
Ferrucci, Luigi
Guralnik, Jack M.
Kiel, Douglas P.
Kritchevsky, Stephen B.
Shardell, Michelle D.
Vassileva, Maria T.
Kenny, Anne M.
TI Strength and Function Response to Clinical Interventions of Older Women
Categorized by Weakness and Low Lean Mass Using Classifications From the
Foundation for the National Institute of Health Sarcopenia Project
SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL
SCIENCES
LA English
DT Article
DE Strength; Function; Sarcopenia; Gait speed; Clinical trials
ID RANDOMIZED CONTROLLED-TRIAL; MUSCLE STRENGTH; PHYSICAL PERFORMANCE;
VITAMIN-D; BODY-COMPOSITION; RELEVANT WEAKNESS; RISK-FACTORS; FRAILTY;
ADULTS; SUPPLEMENTATION
AB Background. The Foundation for the National Institutes of Health Sarcopenia Project developed data-driven cutpoints for clinically meaningful weakness and low lean body mass. This analysis describes strength and function response to interventions based on these classifications.
Methods. In data from four intervention studies, 378 postmenopausal women with baseline and 6-month data were evaluated for change in grip strength, appendicular lean mass corrected for body mass index, leg strength and power, and short physical performance battery (SPPB). Clinical interventions included hormones, exercise, and nutritional supplementation. Differences in outcomes were evaluated between (i) those with and without weakness and (ii) those with weakness and low lean mass or with one but not the other. We stratified analyses by slowness (walking speed <= 0.8 m/s) and by treatment assignment.
Results. The women (72 +/- 7 years; body mass index of 26 +/- 5 kg/m(2)) were weak (33%), had low lean mass (14%), or both (6%). Those with weakness increased grip strength, lost less leg power, and gained SPPB score (p<.05) compared with nonweak participants. Stratified analyses were similar for grip strength and SPPB. With lean mass in the analysis, individuals with weakness had larger gains in grip strength and SPPB scores regardless of low lean mass (p<.01).
Conclusions. Older women with clinically meaningful muscle weakness increased grip strength and SPPB, regardless of the presence of low lean mass following treatment with interventions for frailty. Thus, results suggest that muscle weakness, as defined by the Foundation for the National Institutes of Health Sarcopenia Project, appears to be a treatable symptom.
C1 [Fragala, Maren S.] Univ Cent Florida, Orlando, FL 32816 USA.
[Dam, Thuy-Tien L.] Columbia Univ Coll Phys & Surg, New York, NY 10032 USA.
[Barber, Vanessa; Judge, James O.; Kenny, Anne M.] Univ Connecticut, Ctr Hlth, Farmington, CT 06030 USA.
[Studenski, Stephanie A.; Harris, Tamara B.; Ferrucci, Luigi] NIA, NIH, Bethesda, MD 20892 USA.
[Cawthon, Peggy M.] Calif Pacific Med Ctr, Res Inst, San Francisco, CA USA.
[McLean, Robert R.; Kiel, Douglas P.] Hebrew Senior Life Inst Aging Res, Boston, MA USA.
[McLean, Robert R.; Kiel, Douglas P.] Harvard Univ, Sch Med, Boston, MA USA.
[Guralnik, Jack M.; Shardell, Michelle D.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA.
[Kritchevsky, Stephen B.] Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA.
[Vassileva, Maria T.] Fdn Natl Inst Hlth, Bethesda, MD USA.
RP Kenny, AM (reprint author), Univ Connecticut, Ctr Hlth, Farmington, CT 06030 USA.
EM kenny@uchc.edu
OI Kiel, Douglas/0000-0001-8474-0310
FU National Institute on Aging [1U13AG041583, P30 AG024827]; Food and Drug
Administration; Foundation for the NIH; Abbott Nutrition; Amgen; Eli
Lilly; Merck; Novartis; Dairy Research Institute
FX Funding support for the conference and the work of the consortium was
provided by the National Institute on Aging (1U13AG041583 and P30
AG024827), the Food and Drug Administration, and through grants from the
Foundation for the NIH, made possible by funding from Abbott Nutrition,
Amgen, Eli Lilly, Merck, Novartis, and The Dairy Research Institute.
NR 49
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Z9 10
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 FEB
PY 2015
VL 70
IS 2
BP 202
EP 209
DI 10.1093/gerona/glu110
PG 8
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA CC1RR
UT WOS:000350121100008
PM 25135999
ER
PT J
AU Felisiak-Golabek, A
Wasag, B
Coates, T
Lasota, JP
Miettinen, M
AF Felisiak-Golabek, Anna
Wasag, Bartosz
Coates, Tiffany
Lasota, Jerzy P.
Miettinen, Markku
TI Frequency and Clinicopathologic Profile of PIK3CA Mutant GISTs
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 104th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 21-27, 2015
CL Boston, MA
SP US & Canadian Acad Pathol
C1 NCI, Bethesda, MD 20892 USA.
Med Univ, Gdansk, Poland.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
EI 1530-0285
J9 MODERN PATHOL
JI Mod. Pathol.
PD FEB
PY 2015
VL 28
SU 2
MA 54
BP 17A
EP 17A
PG 1
WC Pathology
SC Pathology
GA CB3BF
UT WOS:000349502200055
ER
PT J
AU Hsi, A
Brown, G
Lee, CC
Schaffer, A
AF Hsi, Andy
Brown, Gregory
Lee, Chyi-Chia
Schaffer, Andras
TI Expression of Master Regulators of Mature T-Cell Differentiation FOXP3,
T-Bet, and GATA-3 in Cutaneous Adult T-Cell Leukemia/Lymphoma By
Immunohistochemistry
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 104th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 21-27, 2015
CL Boston, MA
SP US & Canadian Acad Pathol
C1 Washington Univ, Sch Med, St Louis, MO USA.
NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
EI 1530-0285
J9 MODERN PATHOL
JI Mod. Pathol.
PD FEB
PY 2015
VL 28
SU 2
MA 471
BP 121A
EP 121A
PG 1
WC Pathology
SC Pathology
GA CB3BF
UT WOS:000349502200471
ER
PT J
AU Giubellino, A
Li, A
Lara-Otero, K
Linehan, M
Merino, M
AF Giubellino, Alessio
Li, Ang
Lara-Otero, Karlena
Linehan, Marston
Merino, Maria
TI MicroRNA Profiling of Morphologically Heterogeneous Clear Renal Cell
Carcinoma
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 104th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 21-27, 2015
CL Boston, MA
SP US & Canadian Acad Pathol
C1 [Giubellino, Alessio; Li, Ang; Lara-Otero, Karlena; Linehan, Marston; Merino, Maria] NCI, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
EI 1530-0285
J9 MODERN PATHOL
JI Mod. Pathol.
PD FEB
PY 2015
VL 28
SU 2
MA 886
BP 223A
EP 223A
PG 1
WC Pathology
SC Pathology
GA CB3BF
UT WOS:000349502201224
ER
PT J
AU Merino, M
Ghosh, A
Schmidt, L
Linehan, M
AF Merino, Maria
Ghosh, Arunima
Schmidt, Laura
Linehan, Marston
TI Clonal Analysis of Multi-Focal Tumors in Patients With Birt-Hogg-Dube
Syndrome
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 104th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 21-27, 2015
CL Boston, MA
SP US & Canadian Acad Pathol
C1 NCI, Bethesda, MD 20892 USA.
Frederick Natl Lab, Frederick, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
EI 1530-0285
J9 MODERN PATHOL
JI Mod. Pathol.
PD FEB
PY 2015
VL 28
SU 2
MA 975
BP 245A
EP 245A
PG 1
WC Pathology
SC Pathology
GA CB3BF
UT WOS:000349502201313
ER
PT J
AU Moreno, V
Metwali, A
Linehan, WM
Merino, M
AF Moreno, Vanessa
Metwali, Adam
Linehan, W. Marston
Merino, Maria
TI New and Old Testicular Lesions Associated With VHL Syndrome
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 104th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 21-27, 2015
CL Boston, MA
SP US & Canadian Acad Pathol
C1 [Moreno, Vanessa; Metwali, Adam; Linehan, W. Marston; Merino, Maria] NCI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
EI 1530-0285
J9 MODERN PATHOL
JI Mod. Pathol.
PD FEB
PY 2015
VL 28
SU 2
MA 979
BP 246A
EP 246A
PG 1
WC Pathology
SC Pathology
GA CB3BF
UT WOS:000349502201317
ER
PT J
AU Yan, WS
Young, D
Song, YJ
Chen, YM
Katta, S
Ravindranath, L
Lee, J
Srinivasan, A
Cullen, J
Kagan, J
Srivastava, S
Dobi, A
Rosner, I
McLeod, D
Sesterhenn, I
Srivastava, S
Petrovics, G
AF Yan, Wusheng
Young, Denise
Song, Yingjie
Chen, Yongmei
Katta, Shilpa
Ravindranath, Lakshmi
Lee, Jocelyn
Srinivasan, Alagarsamy
Cullen, Jennifer
Kagan, Jacob
Srivastava, Sudhir
Dobi, Albert
Rosner, Inger
McLeod, David
Sesterhenn, Isabell
Srivastava, Shiv
Petrovics, Gyorgy
TI Optimization of Nanostring Platform for Evaluation of Prostate Cancer
Biomarkers and Therapeutic Targes in FFPE Specimens
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 104th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 21-27, 2015
CL Boston, MA
SP US & Canadian Acad Pathol
C1 Uniformed Serv Univ Hlth Sci, Rockville, MD USA.
NCI, Rockville, MD USA.
Walter Reed Natl Mil Med Ctr, Bethesda, MD USA.
Joint Pathol Ctr, Silver Spring, MD USA.
NR 0
TC 0
Z9 0
U1 1
U2 3
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
EI 1530-0285
J9 MODERN PATHOL
JI Mod. Pathol.
PD FEB
PY 2015
VL 28
SU 2
MA 1070
BP 268A
EP 269A
PG 2
WC Pathology
SC Pathology
GA CB3BF
UT WOS:000349502201408
ER
PT J
AU Yang, ZM
Li, A
Pinto, P
Merino, M
AF Yang, Zhiming
Li, Ang
Pinto, Peter
Merino, Maria
TI microRNA Profiling of Prostate Cancer in Young and Older Man, One or Two
Diseases?
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 104th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 21-27, 2015
CL Boston, MA
SP US & Canadian Acad Pathol
C1 [Yang, Zhiming; Li, Ang; Pinto, Peter; Merino, Maria] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
EI 1530-0285
J9 MODERN PATHOL
JI Mod. Pathol.
PD FEB
PY 2015
VL 28
SU 2
MA 1072
BP 269A
EP 269A
PG 1
WC Pathology
SC Pathology
GA CB3BF
UT WOS:000349502201410
ER
PT J
AU Zheng, XY
Mao, Y
Huang, WH
Kamalakaran, S
Yang, YF
Linehan, WM
Merino, MJ
Zhong, MH
Dimitrova, N
Fallon, J
AF Zheng, Xiaoyong
Mao, Yong
Huang, Weihua
Kamalakaran, Sitharthan
Yang, Youfeng
Linehan, W. Marston
Merino, Maria J.
Zhong, Minghao
Dimitrova, Nevenka
Fallon, John
TI Detecting Additional Chromosomal Translocations in TFE3 Translocation
Renal Cell RCC By RNA-Seq
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 104th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 21-27, 2015
CL Boston, MA
SP US & Canadian Acad Pathol
C1 New York Med Coll, Westchester Cty Med Ctr, Valhalla, NY 10595 USA.
Philips Res North Amer, Briarcliff Manor, NY 20892 USA.
NCI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
EI 1530-0285
J9 MODERN PATHOL
JI Mod. Pathol.
PD FEB
PY 2015
VL 28
SU 2
MA 1080
BP 271A
EP 271A
PG 1
WC Pathology
SC Pathology
GA CB3BF
UT WOS:000349502201418
ER
PT J
AU Gong, SY
Dumitriu, B
Young, N
Maric, I
AF Gong, Shunyou
Dumitriu, Bogdan
Young, Neal
Maric, Irina
TI Evaluation of Phospho-STAT3 Immunohistochemical Stain in Diagnosis of
Marrow Involvement By Large Granular Lymphocytic Leukemia
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 104th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 21-27, 2015
CL Boston, MA
SP US & Canadian Acad Pathol
C1 NCI, Bethesda, MD 20892 USA.
NHLBI, Bethesda, MD 20892 USA.
NIH, Ctr Clin, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
EI 1530-0285
J9 MODERN PATHOL
JI Mod. Pathol.
PD FEB
PY 2015
VL 28
SU 2
MA 1385
BP 346A
EP 346A
PG 1
WC Pathology
SC Pathology
GA CB3BF
UT WOS:000349502202094
ER
PT J
AU Gong, SY
Townsley, D
Hsu, A
Arthur, D
Giri, N
Alter, B
Hickstein, D
Young, N
Braylan, R
Holland, S
Calvo, K
AF Gong, Shunyou
Townsley, Danielle
Hsu, Amy
Arthur, Diane
Giri, Neelam
Alter, Blanche
Hickstein, Dennis
Young, Neal
Braylan, Raul
Holland, Steven
Calvo, Katherine
TI Atypical Myelofibrosis in Patients Harboring Germline GATA2 Mutations
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 104th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 21-27, 2015
CL Boston, MA
SP US & Canadian Acad Pathol
C1 [Gong, Shunyou; Townsley, Danielle; Hsu, Amy; Arthur, Diane; Giri, Neelam; Alter, Blanche; Hickstein, Dennis; Young, Neal; Braylan, Raul; Holland, Steven; Calvo, Katherine] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
EI 1530-0285
J9 MODERN PATHOL
JI Mod. Pathol.
PD FEB
PY 2015
VL 28
SU 2
MA 1384
BP 346A
EP 346A
PG 1
WC Pathology
SC Pathology
GA CB3BF
UT WOS:000349502202093
ER
PT J
AU King, R
Dao, LD
McPhail, E
Jaffe, E
Said, J
Swerdlow, S
Sidhu, J
Hsi, E
Karikehalli, S
Jiang, LY
Gibson, S
Ondrejka, S
Nicolae, A
Macon, W
Castellar, EP
Feldman, AL
AF King, Rebecca
Dao, Linda
McPhail, Ellen
Jaffe, Elaine
Said, Jonathan
Swerdlow, Steven
Sidhu, Jagnzohan
Hsi, Eric
Karikehalli, Shridevi
Jiang, Liuyan
Gibson, Sarah
Ondrejka, Sarah
Nicolae, Alina
Macon, William
Castellar, Edgardo Parrilla
Feldman, Andrew L.
TI Morphology of ALK-Negative Anaplastic Large Cell Lymphomas With DUSP22
Rearrangements
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 104th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 21-27, 2015
CL Boston, MA
SP US & Canadian Acad Pathol
C1 Mayo Clin, Rochester, MN USA.
NCI, Bethesda, MD 20892 USA.
Univ Calif Los Angeles, Los Angeles, CA USA.
Univ Pittsburgh, Pittsburgh, PA USA.
United Hlth Serv Hopsitals, Binghamton, NY USA.
Cleveland Clin, Cleveland, OH 44106 USA.
Centrex Clin Labs, Utica, NY USA.
Univ Washington, Seattle, WA 98195 USA.
Mayo Clin, Jacksonville, FL 32224 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
EI 1530-0285
J9 MODERN PATHOL
JI Mod. Pathol.
PD FEB
PY 2015
VL 28
SU 2
MA 1416
BP 355A
EP 355A
PG 1
WC Pathology
SC Pathology
GA CB3BF
UT WOS:000349502202125
ER
PT J
AU Nicolae, A
Ganapathi, K
Pittaluga, S
Raffeld, M
Jaffe, E
AF Nicolae, Alina
Ganapathi, Karthik
Pittaluga, Stefania
Raffeld, Mark
Jaffe, Elaine
TI Aggressive NK-Cell Leukemia/Lymphoma, EBV-Negative - A Report of 5 Cases
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 104th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 21-27, 2015
CL Boston, MA
SP US & Canadian Acad Pathol
C1 NCI, Bethesda, MD 20892 USA.
Columbia Univ, New York, NY USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
EI 1530-0285
J9 MODERN PATHOL
JI Mod. Pathol.
PD FEB
PY 2015
VL 28
SU 2
MA 1465
BP 368A
EP 368A
PG 1
WC Pathology
SC Pathology
GA CB3BF
UT WOS:000349502202174
ER
PT J
AU Wang, HW
Pittaluga, S
Merino, M
Jaffe, E
AF Wang, Hao-Wei
Pittaluga, Stefania
Merino, Maria
Jaffe, Elaine
TI Primary Malignant Lymphomas of the Urinary Tract
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 104th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 21-27, 2015
CL Boston, MA
SP US & Canadian Acad Pathol
C1 [Wang, Hao-Wei; Pittaluga, Stefania; Merino, Maria; Jaffe, Elaine] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
EI 1530-0285
J9 MODERN PATHOL
JI Mod. Pathol.
PD FEB
PY 2015
VL 28
SU 2
MA 1526
BP 383A
EP 384A
PG 2
WC Pathology
SC Pathology
GA CB3BF
UT WOS:000349502202235
ER
PT J
AU Yousef, G
Butz, H
Szabo, P
Mozes, R
Rotondo, F
Kovacs, K
Patocs, A
AF Yousef, George
Butz, Henriett
Szabo, Peter
Mozes, Roy
Rotondo, Fabio
Kovacs, Kalman
Patocs, Attila
TI Integrative Bioinformatical Analysis of Clear Cell Renal Cell Carcinoma
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 104th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 21-27, 2015
CL Boston, MA
SP US & Canadian Acad Pathol
C1 St Michaels Hosp, Toronto, ON M5B 1W8, Canada.
NCI, NIH, Bethesda, MD 20892 USA.
Hungarian Acad Sci, Budapest, Hungary.
NR 0
TC 0
Z9 0
U1 1
U2 2
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
EI 1530-0285
J9 MODERN PATHOL
JI Mod. Pathol.
PD FEB
PY 2015
VL 28
SU 2
MA 1604
BP 403A
EP 403A
PG 1
WC Pathology
SC Pathology
GA CB3BF
UT WOS:000349502202313
ER
PT J
AU Rosenberg, A
Palmer, M
Merlino, L
Troost, J
Gasim, A
Bagnasco, SM
Avila-Casado, C
Johnstone, D
Hodgin, J
Conway, C
Kopp, J
Nast, C
Barisoni, L
Hewitt, S
AF Rosenberg, Avi
Palmer, Matthew
Merlino, Lino
Troost, Jonathan
Gasim, Adil
Bagnasco, Serena M.
Avila-Casado, Carmen
Johnstone, Duncan
Hodgin, Jeffrey
Conway, Catherine
Kopp, Jeffrey
Nast, Cynthia
Barisoni, Laura
Hewitt, Stephen
TI The NEPTUNE Digital Pathology Protocol Increases Accurate Glomerular
Number Assessment
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 104th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 21-27, 2015
CL Boston, MA
SP US & Canadian Acad Pathol
C1 Johns Hopkins Univ, Baltimore, MD USA.
Univ Penn, Philadelphia, PA 19104 USA.
Univ Miami, Miami, FL USA.
Univ Michigan, Ann Arbor, MI 48109 USA.
Univ N Carolina, Chapel Hill, NC USA.
Univ Hlth Network, Toronto, ON, Canada.
Temple Univ, Philadelphia, PA 19122 USA.
Leica, Vista, CA USA.
NIDDK, Bethesda, MD 20892 USA.
Cedars Sinai Med Ctr, West Hollywood, CA USA.
NCI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
EI 1530-0285
J9 MODERN PATHOL
JI Mod. Pathol.
PD FEB
PY 2015
VL 28
SU 2
MA 1639
BP 411A
EP 412A
PG 2
WC Pathology
SC Pathology
GA CB3BF
UT WOS:000349502202348
ER
PT J
AU Ballester, L
Wang, ZF
Miettinen, M
Rodriguez, F
Raabe, E
Nazarian, J
Eberhart, C
Warren, K
Quezado, M
AF Ballester, Leomar
Wang, Zengfeng
Miettinen, Markku
Rodriguez, Fausto
Raabe, Eric
Nazarian, Javad
Eberhart, Charles
Warren, Katherine
Quezado, Martha
TI Overexpression of the Chromatin Remodeling Proteins ARID1A, BRG1 and
SMARCD3 in Adult and Pediatric Gliomas
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 104th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 21-27, 2015
CL Boston, MA
SP US & Canadian Acad Pathol
C1 NCI, NIH, Bethesda, MD 20892 USA.
Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA.
Childrens Res Inst, Washington, DC USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
EI 1530-0285
J9 MODERN PATHOL
JI Mod. Pathol.
PD FEB
PY 2015
VL 28
SU 2
MA 1711
BP 428A
EP 429A
PG 2
WC Pathology
SC Pathology
GA CB3BF
UT WOS:000349502202419
ER
PT J
AU Ghosh, A
Li, A
Brown, G
Kebebew, E
Merino, M
AF Ghosh, Arunima
Li, Ang
Brown, Gregory
Kebebew, Electron
Merino, Maria
TI Multifocal Pancreatic Neuroendocrine Tumors: Clonality and miRNA
Profiling
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 104th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 21-27, 2015
CL Boston, MA
SP US & Canadian Acad Pathol
C1 [Ghosh, Arunima; Li, Ang; Brown, Gregory; Kebebew, Electron; Merino, Maria] NCI, Rockville, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
EI 1530-0285
J9 MODERN PATHOL
JI Mod. Pathol.
PD FEB
PY 2015
VL 28
SU 2
MA 1771
BP 442A
EP 442A
PG 1
WC Pathology
SC Pathology
GA CB3BF
UT WOS:000349502202479
ER
PT J
AU Rosenberg, A
Pflicke, H
Dreiling, J
Wang, ZF
Ylaya, K
Hewitt, S
Rudloff, U
Miettinen, M
AF Rosenberg, Avi
Pflicke, Holger
Dreiling, Jennifer
Wang, Zeng-Feng
Ylaya, Kris
Hewitt, Stephen
Rudloff, Udo
Miettinen, Markku
TI Elafin Expression in Gastrointestinal Neoplasia and Correlation With
Sensitivity To PI3K/mTOR Inhibitor
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 104th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 21-27, 2015
CL Boston, MA
SP US & Canadian Acad Pathol
C1 Johns Hopkins Univ, Baltimore, MD USA.
NCI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
EI 1530-0285
J9 MODERN PATHOL
JI Mod. Pathol.
PD FEB
PY 2015
VL 28
SU 2
MA 1791
BP 447A
EP 447A
PG 1
WC Pathology
SC Pathology
GA CB3BF
UT WOS:000349502202499
ER
PT J
AU Schlitter, A
Jang, KT
Saka, B
Choi, H
Offerhaus, G
Hruban, R
Zen, Y
Hong, SM
Konzikiewitz, B
Allgaeuer, M
Kloppel, G
Reid, M
Esposito, I
Adsay, V
Basturk, O
AF Schlitter, Anna
Jang, Kee-Taek
Saka, Burcu
Choi, Hyejeong
Offerhaus, G.
Hruban, R.
Zen, Yoh
Hong, Seung-Mo
Konzikiewitz, Bjorn
Allgaeuer, Michael
Kloppel, G.
Reid, M.
Esposito, Irene
Adsay, Volkan
Basturk, Olca
TI Intraductal Tubulopapillary Neoplasms of the Bile Ducts: Further
Immunohistochemical and Molecular Characterization
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 104th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 21-27, 2015
CL Boston, MA
SP US & Canadian Acad Pathol
C1 TUM, Munich, Germany.
SMC, Seoul, South Korea.
EU, Atlanta, GA USA.
Univ Med Ctr, Utrecht, Netherlands.
Johns Hopkins Univ, Baltimore, MD USA.
KCH, London, England.
Asan Med Ctr, Seoul, South Korea.
NCI, NIH, Bethesda, MD 20892 USA.
Wayne State Univ, Detroit, MI USA.
NR 0
TC 0
Z9 0
U1 1
U2 3
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
EI 1530-0285
J9 MODERN PATHOL
JI Mod. Pathol.
PD FEB
PY 2015
VL 28
SU 2
MA 1795
BP 448A
EP 448A
PG 1
WC Pathology
SC Pathology
GA CB3BF
UT WOS:000349502202503
ER
PT J
AU Jawale, R
Williams, K
Yang, H
Lee, M
Otis, C
Pentecost, B
Arcaro, K
AF Jawale, Rahul
Williams, Kristin
Yang, Howard
Lee, Maxwell
Otis, Christopher
Pentecost, Brian
Arcaro, Kathleen
TI DNA Methylation in Endocrine Therapy Resistant Breast Cancer
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 104th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 21-27, 2015
CL Boston, MA
SP US & Canadian Acad Pathol
C1 Baystate Med Ctr, Springfield, MA USA.
UMass Amherst, Amherst, MA USA.
Wadsworth Ctr, Albany, NY USA.
NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 2
U2 2
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
EI 1530-0285
J9 MODERN PATHOL
JI Mod. Pathol.
PD FEB
PY 2015
VL 28
SU 2
MA 1837
BP 458A
EP 459A
PG 2
WC Pathology
SC Pathology
GA CB3BF
UT WOS:000349502203034
ER
PT J
AU Killian, J
Noyes, N
Retnakumar, P
Helman, L
Killian, S
Davis, S
Bilke, S
Su, J
Smith, W
Meltzer, P
AF Killian, Jonathan
Noyes, Natalia
Retnakumar, Parvathy
Helman, Lee
Killian, Scott
Davis, Sean
Bilke, Sven
Su, Joseph
Smith, William
Meltzer, Paul
TI Cellular and Epiallelic Composition of Oral Fluid
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 104th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 21-27, 2015
CL Boston, MA
SP US & Canadian Acad Pathol
C1 NIH, Bethesda, MD 20892 USA.
Univ S Dakota, Vermillion, SD 57069 USA.
Suburban Hosp, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
EI 1530-0285
J9 MODERN PATHOL
JI Mod. Pathol.
PD FEB
PY 2015
VL 28
SU 2
MA 1839
BP 459A
EP 459A
PG 1
WC Pathology
SC Pathology
GA CB3BF
UT WOS:000349502203036
ER
PT J
AU Makhlouf, H
Lubensky, I
Altekruse, S
Mehaffey, M
Sachs, M
Camalier, C
Chuaqui, R
Cozen, W
Biswajit, D
Hernandez, B
Lih, CJ
Lynch, C
McGregor, P
McShane, L
Rohan, JP
Walsh, W
Williams, M
Gillanders, E
Mechanic, L
Schully, S
Carrick, D
AF Makhlouf, Hala
Lubensky, Irina
Altekruse, Sean
Mehaffey, Michele
Sachs, Michael
Camalier, Corinne
Chuaqui, Rodrigo
Cozen, Wendy
Biswajit, Das
Hernandez, Brenda
Lih, Chih-Jian
Lynch, Charles
McGregor, Paul
McShane, Lisa
Rohan, JoyAnn Philips
Walsh, William
Williams, Mickey
Gillanders, Elizabeth
Mechanic, Leah
Schully, Sheri
Carrick, Danielle
TI Effect of Storage Time of FFPE Ovarian Cancer Tissue on DNA Quality for
Next Generation Sequencing
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 104th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 21-27, 2015
CL Boston, MA
SP US & Canadian Acad Pathol
C1 NCI, Rockville, MD USA.
Leidos, Frederick, MD USA.
Univ So Calif, Los Angeles, CA USA.
Univ Hawaii, Ctr Canc, Honolulu, HI 96822 USA.
Univ Iowa, Iowa City, IA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
EI 1530-0285
J9 MODERN PATHOL
JI Mod. Pathol.
PD FEB
PY 2015
VL 28
SU 2
MA 2084
BP 519A
EP 519A
PG 1
WC Pathology
SC Pathology
GA CB3BF
UT WOS:000349502203280
ER
PT J
AU Miles, G
Zhao, YM
Levin, Y
Shetty, J
Tran, B
Mitchell, S
Oberholtzer, JC
Levens, D
AF Miles, George
Zhao, Yongmei
Levin, Yelena
Shetty, Jyoti
Tran, Bao
Mitchell, Stephen
Oberholtzer, J. Carl
Levens, David
TI Multiplex Tissue and Clinical Proteomics By Next-Generation Sequencing
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 104th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 21-27, 2015
CL Boston, MA
SP US & Canadian Acad Pathol
C1 NCI, Bethesda, MD 20892 USA.
Frederick Natl Lab, Frederick, MD USA.
Holy Cross Hosp, Silver Spring, MD USA.
RI Levens, David/C-9216-2009
OI Levens, David/0000-0002-7616-922X
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
EI 1530-0285
J9 MODERN PATHOL
JI Mod. Pathol.
PD FEB
PY 2015
VL 28
SU 2
MA 2089
BP 520A
EP 520A
PG 1
WC Pathology
SC Pathology
GA CB3BF
UT WOS:000349502203285
ER
PT J
AU Rosenberg, A
Armani, M
Fetsch, P
Xi, LQ
Pham, TT
Raffeld, M
Chen, Y
O'Flaherty, N
Stussman, R
Blackler, A
Du, Q
Hanson, J
Roth, M
Filie, A
Rah, M
Emmert-Buck, M
Hipp, J
Tangrea, M
AF Rosenberg, Avi
Armani Irm, Michael
Fetsch, Patricia
Xi, Liqiang
Tina Thu Pham
Raffeld, Mark
Chen, Yun
O'Flaherty, Neil
Stussman, Rebecca
Blackler, Adele
Du, Qiang
Hanson, Jeffrey
Roth, Mark
Filie, Armando
Rah, Michael
Emmert-Buck, Michael
Hipp, Jason
Tangrea, Michael
TI A Do-It-Yourself, High-Throughput Microdissection System for Improving
NGS Data
SO MODERN PATHOLOGY
LA English
DT Meeting Abstract
CT 104th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 21-27, 2015
CL Boston, MA
SP US & Canadian Acad Pathol
C1 Johns Hopkins Sch Med, Baltimore, MD USA.
NCI, Bethesda, MD 20892 USA.
Univ Michigan, Ann Arbor, MI 48109 USA.
Sinai Hosp, Baltimore, MD 21215 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
EI 1530-0285
J9 MODERN PATHOL
JI Mod. Pathol.
PD FEB
PY 2015
VL 28
SU 2
MA 2099
BP 523A
EP 523A
PG 1
WC Pathology
SC Pathology
GA CB3BF
UT WOS:000349502203295
ER
PT J
AU Davies, G
Armstrong, N
Bis, JC
Bressler, J
Chouraki, V
Giddaluru, S
Hofer, E
Ibrahim-Verbaas, CA
Kirin, M
Lahti, J
van der Lee, SJ
Le Hellard, S
Liu, T
Marioni, RE
Oldmeadow, C
Postmus, I
Smith, AV
Smith, JA
Thalamuthu, A
Thomson, R
Vitart, V
Wang, J
Yu, L
Zgaga, L
Zhao, W
Boxall, R
Harris, SE
Hill, WD
Liewald, DC
Luciano, M
Adams, H
Ames, D
Amin, N
Amouyel, P
Assareh, AA
Au, R
Becker, JT
Beiser, A
Berr, C
Bertram, L
Boerwinkle, E
Buckley, BM
Campbell, H
Corley, J
De Jager, PL
Dufouil, C
Eriksson, JG
Espeseth, T
Faul, JD
Ford, I
Gottesman, RF
Griswold, ME
Gudnason, V
Harris, TB
Heiss, G
Hofman, A
Holliday, EG
Huffman, J
Kardia, SLR
Kochan, N
Knopman, DS
Kwok, JB
Lambert, JC
Lee, T
Li, G
Li, SC
Loitfelder, M
Lopez, OL
Lundervold, AJ
Lundqvist, A
Mather, KA
Mirza, SS
Nyberg, L
Oostra, BA
Palotie, A
Papenberg, G
Pattie, A
Petrovic, K
Polasek, O
Psaty, BM
Redmond, P
Reppermund, S
Rotter, JI
Schmidt, H
Schuur, M
Schofield, PW
Scott, RJ
Steen, VM
Stott, DJ
Van Swieten, JC
Taylor, KD
Trollor, J
Trompet, S
Uitterlinden, AG
Weinstein, G
Widen, E
Windham, BG
Jukema, JW
Wright, AF
Wright, MJ
Yang, Q
Amieva, H
Attia, JR
Bennett, DA
Brodaty, H
de Craen, AJM
Hayward, C
Ikram, MA
Lindenberger, U
Nilsson, LG
Porteous, DJ
Raikkonen, K
Reinvang, I
Rudan, I
Sachdev, PS
Schmidt, R
Schofield, PR
Srikanth, V
Starr, JM
Turner, ST
Weir, DR
Wilson, JF
Van Duijn, C
Launer, L
Fitzpatrick, AL
Seshadri, S
Jr, THM
Deary, IJ
AF Davies, G.
Armstrong, N.
Bis, J. C.
Bressler, J.
Chouraki, V.
Giddaluru, S.
Hofer, E.
Ibrahim-Verbaas, C. A.
Kirin, M.
Lahti, J.
van der Lee, S. J.
Le Hellard, S.
Liu, T.
Marioni, R. E.
Oldmeadow, C.
Postmus, I.
Smith, A. V.
Smith, J. A.
Thalamuthu, A.
Thomson, R.
Vitart, V.
Wang, J.
Yu, L.
Zgaga, L.
Zhao, W.
Boxall, R.
Harris, S. E.
Hill, W. D.
Liewald, D. C.
Luciano, M.
Adams, H.
Ames, D.
Amin, N.
Amouyel, P.
Assareh, A. A.
Au, R.
Becker, J. T.
Beiser, A.
Berr, C.
Bertram, L.
Boerwinkle, E.
Buckley, B. M.
Campbell, H.
Corley, J.
De Jager, P. L.
Dufouil, C.
Eriksson, J. G.
Espeseth, T.
Faul, J. D.
Ford, I.
Gottesman, R. F.
Griswold, M. E.
Gudnason, V.
Harris, T. B.
Heiss, G.
Hofman, A.
Holliday, E. G.
Huffman, J.
Kardia, S. L. R.
Kochan, N.
Knopman, D. S.
Kwok, J. B.
Lambert, J-C
Lee, T.
Li, G.
Li, S-C
Loitfelder, M.
Lopez, O. L.
Lundervold, A. J.
Lundqvist, A.
Mather, K. A.
Mirza, S. S.
Nyberg, L.
Oostra, B. A.
Palotie, A.
Papenberg, G.
Pattie, A.
Petrovic, K.
Polasek, O.
Psaty, B. M.
Redmond, P.
Reppermund, S.
Rotter, J. I.
Schmidt, H.
Schuur, M.
Schofield, P. W.
Scott, R. J.
Steen, V. M.
Stott, D. J.
Van Swieten, J. C.
Taylor, K. D.
Trollor, J.
Trompet, S.
Uitterlinden, A. G.
Weinstein, G.
Widen, E.
Windham, B. G.
Jukema, J. W.
Wright, A. F.
Wright, M. J.
Yang, Q.
Amieva, H.
Attia, J. R.
Bennett, D. A.
Brodaty, H.
de Craen, A. J. M.
Hayward, C.
Ikram, M. A.
Lindenberger, U.
Nilsson, L-G
Porteous, D. J.
Raikkonen, K.
Reinvang, I.
Rudan, I.
Sachdev, P. S.
Schmidt, R.
Schofield, P. R.
Srikanth, V.
Starr, J. M.
Turner, S. T.
Weir, D. R.
Wilson, J. F.
Van Duijn, C.
Launer, L.
Fitzpatrick, A. L.
Seshadri, S.
Jr, T. H. Mosley
Deary, I. J.
CA Generation Scotland
TI Genetic contributions to variation in general cognitive function: a
meta-analysis of genome-wide association studies in the CHARGE
consortium (N=53 949)
SO MOLECULAR PSYCHIATRY
LA English
DT Article
ID CPG-BINDING PROTEIN-2; ALZHEIMERS-DISEASE; HUMAN INTELLIGENCE;
APOLIPOPROTEIN-E; OLD-AGE; SUSCEPTIBILITY LOCI; IDENTIFIES VARIANTS;
TEST BATTERIES; TYPE-4 ALLELE; HUMAN HEIGHT
AB General cognitive function is substantially heritable across the human life course from adolescence to old age. We investigated the genetic contribution to variation in this important, health-and well-being-related trait in middle-aged and older adults. We conducted a meta-analysis of genome-wide association studies of 31 cohorts (N = 53 949) in which the participants had undertaken multiple, diverse cognitive tests. A general cognitive function phenotype was tested for, and created in each cohort by principal component analysis. We report 13 genome-wide significant single-nucleotide polymorphism (SNP) associations in three genomic regions, 6q16.1, 14q12 and 19q13.32 (best SNP and closest gene, respectively: rs10457441, P = 3.93 x 10(-9), MIR2113; rs17522122, P = 2.55 x 10(-8), AKAP6; rs10119, P = 5.67 x 10(-9), APOE/TOMM40). We report one gene-based significant association with the HMGN1 gene located on chromosome 21 (P = 1x10(-6)). These genes have previously been associated with neuropsychiatric phenotypes. Meta-analysis results are consistent with a polygenic model of inheritance. To estimate SNP-based heritability, the genome-wide complex trait analysis procedure was applied to two large cohorts, the Atherosclerosis Risk in Communities Study (N = 6617) and the Health and Retirement Study (N = 5976). The proportion of phenotypic variation accounted for by all genotyped common SNPs was 29% (s.e. = 5%) and 28% (s.e. = 7%), respectively. Using polygenic prediction analysis, similar to 1.2% of the variance in general cognitive function was predicted in the Generation Scotland cohort (N = 5487; P = 1.5 x 10(-17)). In hypothesis-driven tests, there was significant association between general cognitive function and four genes previously associated with Alzheimer's disease: TOMM40, APOE, ABCG1 and MEF2C.
C1 [Davies, G.; Marioni, R. E.; Harris, S. E.; Liewald, D. C.; Luciano, M.; Porteous, D. J.; Starr, J. M.; Deary, I. J.] Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh EH8 9JZ, Midlothian, Scotland.
[Davies, G.; Hill, W. D.; Luciano, M.; Corley, J.; Pattie, A.; Redmond, P.; Deary, I. J.] Univ Edinburgh, Dept Psychol, Edinburgh EH8 9JZ, Midlothian, Scotland.
[Armstrong, N.] Univ Sydney, Sch Math & Stat, Sydney, NSW 2006, Australia.
[Bis, J. C.; Li, G.; Psaty, B. M.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA.
[Bressler, J.; Boerwinkle, E.] Univ Texas Hlth Sci Ctr Houston, Human Genet Ctr, Sch Publ Hlth, Houston, TX 77030 USA.
[Chouraki, V.; Amouyel, P.; Lambert, J-C] Inst Pasteur, Inserm UMR744, Unite Epidemiol & Sante Publ, F-59019 Lille, France.
[Chouraki, V.; Au, R.; Beiser, A.; Weinstein, G.; Seshadri, S.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA.
[Giddaluru, S.; Le Hellard, S.; Steen, V. M.] Univ Bergen, KG Jebsen Ctr Psychosis Res, Bergen, Norway.
[Giddaluru, S.; Le Hellard, S.; Steen, V. M.] Univ Bergen, Norwegian Ctr Mental Disorders Res NORMENT, Dept Clin Sci, Bergen, Norway.
[Giddaluru, S.; Le Hellard, S.; Steen, V. M.] Haukeland Hosp, Dr Einar Martens Res Grp Biol Psychiat, Ctr Med Genet & Mol Med, N-5021 Bergen, Norway.
[Hofer, E.; Loitfelder, M.; Petrovic, K.; Schmidt, H.; Schmidt, R.] Med Univ Graz, Dept Neurol, Graz, Austria.
[Hofer, E.] Med Univ Graz, Inst Med Informat Stat & Documentat, Graz, Austria.
[Ibrahim-Verbaas, C. A.; Schuur, M.; Van Swieten, J. C.; Ikram, M. A.] Erasmus Univ, Dept Neurol, Med Ctr, Rotterdam, Netherlands.
[Ibrahim-Verbaas, C. A.; van der Lee, S. J.; Amin, N.; Oostra, B. A.; Schuur, M.; Van Duijn, C.] Erasmus Univ, Genet Epidemiol Unit, Dept Epidemiol, Med Ctr, Rotterdam, Netherlands.
[Kirin, M.; Campbell, H.; Rudan, I.; Wilson, J. F.] Univ Edinburgh, Ctr Populat Hlth Sci, Edinburgh EH8 9JZ, Midlothian, Scotland.
[Lahti, J.; Raikkonen, K.] Univ Helsinki, Inst Behav Sci, Helsinki, Finland.
[Lahti, J.; Eriksson, J. G.] Folkhalsan Res Ctr, Helsinki, Finland.
[Liu, T.; Li, S-C; Papenberg, G.; Lindenberger, U.] Max Planck Inst Human Dev, Berlin, Germany.
[Liu, T.; Bertram, L.] Max Planck Inst Mol Genet, D-14195 Berlin, Germany.
[Marioni, R. E.; Boxall, R.; Harris, S. E.; Porteous, D. J.] Univ Edinburgh, Med Genet Sect, Ctr Genom & Expt Med, Inst Genet & Mol Med,Western Gen Hosp, Edinburgh EH8 9JZ, Midlothian, Scotland.
[Marioni, R. E.] Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia.
[Oldmeadow, C.; Holliday, E. G.; Scott, R. J.; Attia, J. R.] Univ Newcastle, Hunter Med Res Inst, Newcastle, NSW 2300, Australia.
[Oldmeadow, C.; Holliday, E. G.; Scott, R. J.; Attia, J. R.] Univ Newcastle, Fac Hlth, Newcastle, NSW 2300, Australia.
[Postmus, I.; Trompet, S.; de Craen, A. J. M.] Leiden Univ, Dept Gerontol & Geriatr, Med Ctr, Leiden, Netherlands.
[Postmus, I.; de Craen, A. J. M.] Netherlands Consortium Hlth Ageing, Leiden, Netherlands.
[Smith, A. V.; Gudnason, V.] Iceland Heart Assoc, Kopavogur, Iceland.
[Smith, A. V.; Gudnason, V.] Univ Iceland, Reykjavik, Iceland.
[Smith, J. A.; Zhao, W.; Kardia, S. L. R.] Univ Michigan, Dept Epidemiol, Ann Arbor, MI 48109 USA.
[Thalamuthu, A.; Assareh, A. A.; Kochan, N.; Lee, T.; Mather, K. A.; Reppermund, S.; Trollor, J.; Brodaty, H.; Sachdev, P. S.] Univ New S Wales, Sch Psychiat, Ctr Hlth Brain Ageing, Sydney, NSW, Australia.
[Thomson, R.; Srikanth, V.] Menzies Res Inst, Hobart, Tas, Australia.
[Vitart, V.; Huffman, J.; Wright, A. F.; Hayward, C.] Univ Edinburgh, MRC Human Genet Unit, Inst Genet & Mol Med, Edinburgh EH8 9JZ, Midlothian, Scotland.
[Wang, J.; Au, R.; Beiser, A.; Weinstein, G.; Yang, Q.; Seshadri, S.] Framingham Heart Dis Epidemiol Study, Framingham, MA USA.
[Wang, J.; Yang, Q.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Yu, L.; Bennett, D. A.] Rush Univ, Med Ctr, Rush Alzheimers Dis Ctr, Chicago, IL 60612 USA.
[Zgaga, L.] Univ Dublin Trinity Coll, Dept Publ Hlth & Primary Care, Dublin 2, Ireland.
[Zgaga, L.] Univ Zagreb, Sch Med, Andrija Stampar Sch Publ Hlth, Zagreb 41001, Croatia.
[Adams, H.; Hofman, A.; Mirza, S. S.; Uitterlinden, A. G.; Ikram, M. A.] Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands.
[Adams, H.; Amin, N.; Hofman, A.; Mirza, S. S.; Uitterlinden, A. G.; Ikram, M. A.; Van Duijn, C.] Netherlands Consortium Hlth Ageing, Leiden, Netherlands.
[Ames, D.] Royal Melbourne Hosp, Natl Ageing Res Inst, Melbourne, Vic, Australia.
[Ames, D.] Univ Melbourne, Acad Unit Psychiat Old Age, St Georges Hosp, Kew, Australia.
[Becker, J. T.; Lopez, O. L.] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15260 USA.
[Becker, J. T.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA.
[Becker, J. T.] Univ Pittsburgh, Dept Psychol, Pittsburgh, PA 15260 USA.
[Berr, C.] INSERM, U106, Montpellier, France.
[Berr, C.] Univ Montpellier I, Montpellier, France.
[Bertram, L.] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Fac Med, London, England.
[Boerwinkle, E.] Univ Texas Hlth Sci Ctr Houston, Brown Fdn Inst Mol Med Prevent Human Dis, Houston, TX 77030 USA.
[Boerwinkle, E.] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA.
[Buckley, B. M.] Natl Univ Ireland Univ Coll Cork, Dept Pharmacol & Therapeut, Cork, Ireland.
[De Jager, P. L.] Brigham & Womens Hosp, Program Translat NeuroPsychiat Genom, Dept Neurol, Boston, MA 02115 USA.
[De Jager, P. L.] Harvard Univ, Sch Med, Boston, MA USA.
[De Jager, P. L.] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.
[Dufouil, C.] INSERM, U708, Neuroepidemiol, Paris, France.
[Dufouil, C.; Amieva, H.] Univ Bordeaux Segalen, INSERM, U897, Bordeaux, France.
[Eriksson, J. G.] Natl Inst Hlth & Welf, Helsinki, Finland.
[Eriksson, J. G.] Univ Helsinki, Dept Gen Practice & Primary Hlth Care, Helsinki, Finland.
[Eriksson, J. G.] Univ Helsinki, Cent Hosp, Unit Gen Practice, Helsinki, Finland.
[Espeseth, T.] Oslo Univ Hosp, KG Jebsen Ctr Psychosis Res, Norwegian Ctr Mental Disorders Res NORMENT, Div Mental Hlth & Addict, Oslo, Norway.
[Espeseth, T.] Univ Oslo, Inst Clin Med, Oslo, Norway.
[Espeseth, T.; Reinvang, I.] Univ Oslo, Dept Psychol, Oslo, Norway.
[Faul, J. D.; Weir, D. R.] Univ Michigan, Inst Social Res, Survey Res Ctr, Ann Arbor, MI USA.
[Ford, I.] Robertson Ctr Biostat, Glasgow, Lanark, Scotland.
[Porteous, D. J.; Generation Scotland] Univ Edinburgh, Generat Scotland, Ctr Genom & Expt Med, Inst Genet & Mol Med,Western Gen Hosp, Edinburgh EH8 9JZ, Midlothian, Scotland.
[Gottesman, R. F.] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD USA.
[Griswold, M. E.] Univ Mississippi, Med Ctr, Ctr Biostat & Bioinformat, Jackson, MS 39216 USA.
[Harris, T. B.; Launer, L.] NIA, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
[Heiss, G.] Univ N Carolina, Dept Epidemiol, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA.
[Kochan, N.; Lee, T.; Sachdev, P. S.] Prince Wales Hosp, Neuropsychiat Inst, Sydney, NSW, Australia.
[Knopman, D. S.] Mayo Clin, Dept Neurol, Rochester, MN USA.
[Kwok, J. B.] Neurosci Res Australia, Randwick, NSW, Australia.
[Kwok, J. B.] Univ New S Wales, Sch Med Sci, Sydney, NSW, Australia.
[Li, S-C] Tech Univ Dresden, D-01062 Dresden, Germany.
[Lundervold, A. J.] Univ Bergen, Dept Biol & Med Psychol, Bergen, Norway.
[Lundervold, A. J.] Haraldsplass Deaconess Hosp, Kavli Res Ctr Aging & Dementia, Bergen, Norway.
[Lundervold, A. J.] Univ Bergen, KG Jebsen Ctr Res Neuropsychiat Disorders, Bergen, Norway.
[Lundqvist, A.; Nyberg, L.] Umea Univ, Umea Ctr Funct Brain Imaging UFBI, Umea, Sweden.
[Nyberg, L.] Umea Univ, Dept Radiat Sci, Umea, Sweden.
[Nyberg, L.] Umea Univ, Dept Integrat Med Biol, Umea, Sweden.
[Palotie, A.] Wellcome Trust Genome Campus, Wellcome Trust Sanger Inst, Cambridge, England.
[Palotie, A.; Widen, E.] Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki, Finland.
[Palotie, A.] Univ Helsinki, Dept Med Genet, Helsinki, Finland.
[Palotie, A.] Univ Cent Hosp, Helsinki, Finland.
[Papenberg, G.] Stockholm Univ, Aging Res Ctr, Karolinska Inst, S-10691 Stockholm, Sweden.
[Polasek, O.] Univ Split, Fac Med, Dept Publ Hlth, Split, Croatia.
[Psaty, B. M.; Fitzpatrick, A. L.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Psaty, B. M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA.
[Psaty, B. M.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Unit, Seattle, WA USA.
[Rotter, J. I.; Taylor, K. D.] Harbor UCLA Med Ctr, Inst Translat Genom, Los Angeles, CA USA.
[Rotter, J. I.; Taylor, K. D.] Harbor UCLA Med Ctr, Populat Sci Los Angeles BioMed Res Inst, Los Angeles, CA USA.
[Rotter, J. I.] Harbor UCLA Med Ctr, Div Genet Outcomes, Dept Pediat, Los Angeles, CA USA.
[Schmidt, H.] Med Univ Graz, Ctr Mol Med, Inst Mol Biol & Biochem, Graz, Austria.
[Schofield, P. W.] Univ Newcastle, Sch Med & Publ Hlth, Newcastle, NSW 2300, Australia.
[Stott, D. J.] Univ Glasgow, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland.
[Taylor, K. D.] Harbor UCLA Med Ctr, Dept Pediat, Los Angeles, CA USA.
[Trollor, J.] Univ New S Wales, Sch Psychiat, Dept Dev Disabil Neuropsychiat, Sydney, NSW, Australia.
[Trollor, J.] Leiden Univ, Dept Cardiol, Med Ctr, Leiden, Netherlands.
[Uitterlinden, A. G.] Erasmus Univ, Dept Internal Med, Med Ctr, Rotterdam, Netherlands.
[Windham, B. G.; Jr, T. H. Mosley] Univ Mississippi, Med Ctr, Dept Med, Div Geriatr, Jackson, MS 39216 USA.
[Jukema, J. W.] Durrer Ctr Cardiogenet Res, Amsterdam, Netherlands.
[Jukema, J. W.] Interuniv Cardiol Inst Netherlands, Utrecht, Netherlands.
[Wright, M. J.] QIMR Berghofer Med Res Inst, Neuroimaging Genet Grp, Brisbane, Qld, Australia.
[Brodaty, H.] Univ New S Wales, Dementia Collaborat Res Ctr, Sydney, NSW, Australia.
[Ikram, M. A.] Erasmus Univ, Med Ctr, Dept Radiol, Rotterdam, Netherlands.
[Nilsson, L-G] Karolinska Inst, ARC, Stockholm, Sweden.
[Nilsson, L-G] Umea Univ, UFBI, Umea, Sweden.
[Schofield, P. R.] Neurosci Res Australia, Sydney, NSW, Australia.
[Schofield, P. R.] Univ New S Wales, Fac Med, Sydney, NSW, Australia.
[Srikanth, V.] Monash Univ, Stroke & Ageing Res, Southern Clin Sch, Med, Melbourne, Vic 3004, Australia.
[Starr, J. M.] Univ Edinburgh, Alzheimer Scotland Dementia Res Ctr, Edinburgh EH8 9JZ, Midlothian, Scotland.
[Turner, S. T.] Mayo Clin, Dept Internal Med, Div Nephrol & Hypertens, Rochester, MN USA.
[Fitzpatrick, A. L.] Univ Washington, Dept Global Hlth, Seattle, WA 98195 USA.
RP Davies, G (reprint author), Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Dept Psychol, 7 George Sq, Edinburgh EH8 9JZ, Midlothian, Scotland.
EM i.deary@ed.ac.uk
RI Lambert, jean-charles/A-9553-2014; Smith, Albert/K-5150-2015; Nyberg,
Lars/C-2514-2009; lambert, jean-charles/F-8787-2013; Gudnason,
Vilmundur/K-6885-2015; Wilson, James F/A-5704-2009; Luciano,
Michelle/F-7277-2010; Thomson, Russell/H-5653-2012; Li,
Shu-Chen/K-7838-2012; Polasek, Ozren/B-6002-2011; Wright,
Margaret/A-4560-2016; Bertram, Lars/K-3889-2015
OI Seshadri, Sudha/0000-0001-6135-2622; Zgaga, Lina/0000-0003-4089-9703;
van Swieten, John /0000-0001-6278-6844; Sachdev,
Perminder/0000-0002-9595-3220; Beiser, Alexa/0000-0001-8551-7778; Smith,
Jennifer/0000-0002-3575-5468; Lahti, Jari/0000-0002-4310-5297; Lambert,
jean-charles/0000-0003-0829-7817; Smith, Albert/0000-0003-1942-5845;
Nyberg, Lars/0000-0002-3367-1746; Gudnason,
Vilmundur/0000-0001-5696-0084; Wilson, James F/0000-0001-5751-9178;
Luciano, Michelle/0000-0003-0935-7682; Thomson,
Russell/0000-0003-4949-4120; Li, Shu-Chen/0000-0002-5520-5789; Chouraki,
Vincent/0000-0002-4698-1794; Polasek, Ozren/0000-0002-5765-1862; Wright,
Margaret/0000-0001-7133-4970; Bertram, Lars/0000-0002-0108-124X
FU Zoll LifeCor
FX Bruce M Psaty serves on a DSMB for a clinical trial of a device funded
by the manufacturer (Zoll LifeCor). All other authors declare no
conflict of interest.
NR 84
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U1 6
U2 41
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 FEB
PY 2015
VL 20
IS 2
BP 183
EP 192
DI 10.1038/mp.2014.188
PG 10
WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry
SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry
GA CB9XE
UT WOS:000349986700007
PM 25644384
ER
PT J
AU Leng, Y
Wang, Z
Tsai, LK
Leeds, P
Fessler, EB
Wang, J
Chuang, DM
AF Leng, Y.
Wang, Z.
Tsai, L-K
Leeds, P.
Fessler, E. B.
Wang, J.
Chuang, D-M
TI FGF-21, a novel metabolic regulator, has a robust neuroprotective role
and is markedly elevated in neurons by mood stabilizers
SO MOLECULAR PSYCHIATRY
LA English
DT Article
DE FGF-21; GSK-3 inhibitor; HDAC inhibitor; lithium; neuroprotection;
valproic acid
ID C6 GLIOMA-CELLS; MEDIATED PHOSPHOINOSITIDE TURNOVER; INCREASES
ENERGY-EXPENDITURE; CEREBELLAR GRANULE CELLS; BIPOLAR DISORDER; INSULIN
SENSITIVITY; VALPROIC ACID; PHARMACOLOGICAL CHARACTERIZATION;
NERVOUS-SYSTEM; CALCIUM INFLUX
AB Fibroblast growth factor-21 (FGF-21) is a new member of the FGF super-family and an important endogenous regulator of glucose and lipid metabolism. It has been proposed as a therapeutic target for diabetes and obesity. Its function in the central nervous system (CNS) remains unknown. Previous studies from our laboratory demonstrated that aging primary neurons are more vulnerable to glutamate-induced excitotoxicity, and that co-treatment with the mood stabilizers lithium and valproic acid (VPA) induces synergistic neuroprotective effects. This study sought to identify molecule(s) involved in these synergistic effects. We found that FGF-21 mRNA was selectively and markedly elevated by co-treatment with lithium and VPA in primary rat brain neurons. FGF-21 protein levels were also robustly increased in neuronal lysates and culture medium following lithium-VPA co-treatment. Combining glycogen synthase kinase-3 (GSK-3) inhibitors with VPA or histone deacetylase (HDAC) inhibitors with lithium synergistically increased FGF-21 mRNA levels, supporting that synergistic effects of lithium and VPA are mediated via GSK-3 and HDAC inhibition, respectively. Exogenous FGF-21 protein completely protected aging neurons from glutamate challenge. This neuroprotection was associated with enhanced Akt-1 activation and GSK-3 inhibition. Lithium-VPA co-treatment markedly prolonged lithium-induced Akt-1 activation and augmented GSK-3 inhibition. Akt-1 knockdown markedly decreased FGF-21 mRNA levels and reduced the neuroprotection induced by FGF-21 or lithium-VPA co-treatment. In addition, FGF-21 knockdown reduced lithium-VPA co-treatment-induced Akt-1 activation and neuroprotection against excitotoxicity. Together, our novel results suggest that FGF-21 is a key mediator of the effects of these mood stabilizers and a potential new therapeutic target for CNS disorders.
C1 [Leng, Y.; Wang, Z.; Tsai, L-K; Leeds, P.; Fessler, E. B.; Wang, J.; Chuang, D-M] NIMH, Mol Neurobiol Sect, NIH, Bethesda, MD 20892 USA.
RP Chuang, DM (reprint author), NIMH, Mol Neurobiol Sect, NIH, 10 Ctr Dr,MSC 1363, Bethesda, MD 20892 USA.
EM chuang@mail.nih.gov
OI Tsai, Li-Kai/0000-0001-8420-6951
FU Intramural Research Program of the National Institute of Mental Health,
National Institutes of Health (IRP-NIMH-NIH)
FX This work was supported by the Intramural Research Program of the
National Institute of Mental Health, National Institutes of Health
(IRP-NIMH-NIH). We thank the members of the Molecular Neurobiology
Section, NIMH, NIH for their support, and Ioline Henter for critical
reading and editing of the manuscript.
NR 44
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U1 4
U2 10
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 FEB
PY 2015
VL 20
IS 2
BP 215
EP 223
DI 10.1038/mp.2013.192
PG 9
WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry
SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry
GA CB9XE
UT WOS:000349986700011
PM 24468826
ER
PT J
AU Shaw, P
Sharp, W
Sudre, G
Wharton, A
Greenstein, D
Raznahan, A
Evans, A
Chakravarty, MM
Lerch, JP
Rapoport, J
AF Shaw, P.
Sharp, W.
Sudre, G.
Wharton, A.
Greenstein, D.
Raznahan, A.
Evans, A.
Chakravarty, M. M.
Lerch, J. P.
Rapoport, J.
TI Subcortical and cortical morphological anomalies as an endophenotype in
obsessive-compulsive disorder
SO MOLECULAR PSYCHIATRY
LA English
DT Article
DE endophenotypes; genetics; neuroanatomy; obsessive-compulsive disorder;
orbitofrontal cortex; striatum
ID HUMAN CEREBRAL-CORTEX; DEFAULT-MODE NETWORK; UNAFFECTED RELATIVES;
FUNCTIONAL CONNECTIVITY; EXECUTIVE DYSFUNCTIONS; BRAIN ACTIVATION; SHAPE
DEFORMITY; VOLUME; THICKNESS; TWINS
AB Endophentoypes, quantifiable traits lying on the causal chain between a clinical phenotype and etiology, can be used to accelerate genomic discovery in obsessive-compulsive disorder (OCD). Here we identify the neuroanatomic changes that are shared by 22 OCD adult and adolescent patients and 25 of their unaffected siblings who are at genetic risk for the disorder. Comparisons were made against 47 age and sex matched healthy controls. We defined the surface morphology of the striatum, globus pallidus and thalamus, and thickness of the cerebral cortex. Patients with OCD show significant surface expansion compared with healthy controls, following adjustment for multiple comparisons, in interconnected regions of the caudate, thalamus and right orbitofrontal cortex. Their unaffected siblings show similar, significant expansion, most marked in the ventromedial caudate bilaterally, the right pulvinar thalamic nucleus and the right orbitofrontal cortex. These regions define a network that has been consistently implicated in OCD. In addition, both patients with OCD and unaffected siblings showed similar increased thickness of the right precuneus, which receives rich input from the thalamic pulvinar nuclei and the left medial temporal cortex. Anatomic change within the orbitofrontostriatal and posterior brain circuitry thus emerges as a promising endophenotype for OCD.
C1 [Shaw, P.; Sudre, G.; Wharton, A.] NHGRI, Sect Neurobehav Clin Res, Social & Behav Res Branch, Bethesda, MD 20892 USA.
[Shaw, P.; Sharp, W.; Greenstein, D.; Raznahan, A.; Rapoport, J.] NIMH, Intramural Program, Bethesda, MD 20892 USA.
[Evans, A.] McGill Univ, Neuroimaging Inst & Hosp, Brain Imaging Ctr, Montreal, PQ, Canada.
[Chakravarty, M. M.] Ctr Addict & Mental Hlth, Res Imaging Ctr, Kimel Family Imaging Genet Res Lab, Toronto, ON, Canada.
[Chakravarty, M. M.] Univ Toronto, Dept Psychiat, Toronto, ON, Canada.
[Chakravarty, M. M.] Univ Toronto, Inst Biomat & Biomed Engn, Toronto, ON, Canada.
[Lerch, J. P.] Hosp Sick Children, Program Neurosci & Mental Hlth, Toronto, ON M5G 1X8, Canada.
[Lerch, J. P.] Univ Toronto, Dept Med Biophys, Toronto, ON, Canada.
RP Shaw, P (reprint author), NHGRI, Sect Neurobehav Clin Res, Social & Behav Res Branch, Bldg 31,B1 B37, Bethesda, MD 20892 USA.
EM shawp@mail.nih.gov
FU Intramural Program of the National Human Genome Research Institute;
Intramural Program of the National Institute of Mental Health
FX The study was funded by the Intramural Programs of the National Human
Genome Research Institute and the National Institute of Mental Health.
NR 65
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U1 0
U2 19
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 FEB
PY 2015
VL 20
IS 2
BP 224
EP 231
DI 10.1038/mp.2014.3
PG 8
WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry
SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry
GA CB9XE
UT WOS:000349986700012
PM 24514568
ER
PT J
AU Xu, P
Stevens, ED
French, AD
Kovac, P
AF Xu, Peng
Stevens, Edwin D.
French, Alfred D.
Kovac, Pavol
TI Synthesis and Molecular Structure of the 5-Methoxycarbonylpentyl
alpha-Glycoside of the Upstream, Terminal Moiety of the O-Specific
Polysaccharide of Vibrio cholerae O1, Serotype Inaba
SO MOLECULES
LA English
DT Article
ID CRYSTAL-STRUCTURE; THERMODYNAMIC CONTROL; OGAWA; HEXASACCHARIDE;
ANTIGEN; UNIT; O-1; O/1
AB The trimethylsilyl trifluoromethanesulfonate (TMSOTf)-catalyzed reaction of methyl 6-hydroxyhexanoate with 3-O-benzyl-4-(2,4-di-O-acetyl-3-deoxy-l-glycero-tetronamido)-4,6-dideoxy-2-O-levulinoyl-alpha-d-mannopyranosyl trichloroacetimidate followed by a two-step deprotection (hydrogenolysis over Pd/C catalyst and Zemplen deacylation, to simultaneously remove the acetyl and levulinoyl groups) gave 5-(methoxycarbonyl)pentyl 4-(3-deoxy-l-glycero-tetronamido)-4,6-dideoxy-alpha-d-mannopyranoside. The structure of the latter, for which crystals were obtained in the analytically pure state for the first time, followed from its NMR and high-resolution mass spectra and was confirmed by X-ray crystallography. The molecule has two approximately linear components; a line through the aglycon intersects a line through the mannosyl and tetronylamido groups at 120 degrees. The crystal packing separates the aglycon groups from the tetronylamido and mannosyl groups, with only C-H horizontal ellipsis O hydrogen bonding among the aglycon groups and N-H horizontal ellipsis O, O-H horizontal ellipsis O and C-H horizontal ellipsis O links among the tetronylamido and mannosyl groups. A carbonyl oxygen atom accepts the strongest O-H horizontal ellipsis O hydrogen bond and two strong C-H horizontal ellipsis O hydrogen bonds. The geometric properties were compared with those of related molecules.
C1 [Xu, Peng; Kovac, Pavol] NIDDK, LBC, NIH, Bethesda, MD 20892 USA.
[Stevens, Edwin D.] Western Kentucky Univ, Dept Chem, Bowling Green, KY 42101 USA.
[French, Alfred D.] USDA, So Reg Res Ctr, New Orleans, LA 70124 USA.
RP Kovac, P (reprint author), NIDDK, LBC, NIH, Bethesda, MD 20892 USA.
EM xup3@mail.nih.gov; Edwin.Stevens@wku.edu; Al.French@ars.usda.gov;
kpn@helix.nih.gov
FU Intramural Research Program of the National Institutes of Health (NIH);
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
FX This research was supported by the Intramural Research Program of the
National Institutes of Health (NIH) and National Institute of Diabetes
and Digestive and Kidney Diseases (NIDDK). The crystallography was
carried out at the University of New Orleans.
NR 18
TC 0
Z9 0
U1 2
U2 3
PU MDPI AG
PI BASEL
PA POSTFACH, CH-4005 BASEL, SWITZERLAND
SN 1420-3049
J9 MOLECULES
JI Molecules
PD FEB
PY 2015
VL 20
IS 2
BP 2892
EP 2902
DI 10.3390/molecules20022892
PG 11
WC Chemistry, Organic
SC Chemistry
GA CD0GH
UT WOS:000350748200066
PM 25679049
ER
PT J
AU Kenny, HA
Lal-Nag, M
White, EA
Shen, M
Chiang, CY
Mitra, AK
Zhang, YL
Curtis, M
Schryver, EM
Bettis, S
Jadhav, A
Boxer, MB
Li, ZY
Ferrer, M
Lengyel, E
AF Kenny, Hilary A.
Lal-Nag, Madhu
White, Erin A.
Shen, Min
Chiang, Chun-Yi
Mitra, Anirban K.
Zhang, Yilin
Curtis, Marion
Schryver, Elizabeth M.
Bettis, Sam
Jadhav, Ajit
Boxer, Matthew B.
Li, Zhuyin
Ferrer, Marc
Lengyel, Ernst
TI Quantitative high throughput screening using a primary human
three-dimensional organotypic culture predicts in vivo efficacy
SO NATURE COMMUNICATIONS
LA English
DT Article
ID OVARIAN-CANCER METASTASIS; TUMOR MICROENVIRONMENT; MESOTHELIAL CELLS;
DRUG DISCOVERY; SPHEROID MODEL; VITRO; FIBRONECTIN; FIBROBLASTS;
PROGRESSION; INVASION
AB The tumour microenvironment contributes to cancer metastasis and drug resistance. However, most high throughput screening (HTS) assays for drug discovery use cancer cells grown in monolayers. Here we show that a multilayered culture containing primary human fibroblasts, mesothelial cells and extracellular matrix can be adapted into a reliable 384- and 1,536-multi-well HTS assay that reproduces the human ovarian cancer (OvCa) metastatic microenvironment. We validate the identified inhibitors in secondary in vitro and in vivo biological assays using three OvCa cell lines: HeyA8, SKOV3ip1 and Tyk-nu. The active compounds directly inhibit at least two of the three OvCa functions: adhesion, invasion and growth. In vivo, these compounds prevent OvCa adhesion, invasion and metastasis, and improve survival in mouse models. Collectively, these data indicate that a complex three-dimensional culture of the tumour microenvironment can be adapted for quantitative HTS and may improve the disease relevance of assays used for drug screening.
C1 [Kenny, Hilary A.; White, Erin A.; Chiang, Chun-Yi; Mitra, Anirban K.; Zhang, Yilin; Curtis, Marion; Schryver, Elizabeth M.; Lengyel, Ernst] Univ Chicago, Dept Obstet & Gynecol, Sect Gynecol Oncol, Chicago, IL 60637 USA.
[Lal-Nag, Madhu; Shen, Min; Jadhav, Ajit; Boxer, Matthew B.; Li, Zhuyin; Ferrer, Marc] NIH, Div Preclin Innovat, NCATS, Rockville, MD 20850 USA.
[Bettis, Sam] Univ Chicago, Inst Genom & Syst Biol, Chicago, IL 60637 USA.
[Li, Zhuyin] Bristol Myers Squibb Co, Lead Discovery & Optimizat, Wallingford, CT 06492 USA.
RP Kenny, HA (reprint author), Univ Chicago, Dept Obstet & Gynecol, Sect Gynecol Oncol, 5841 South Maryland Ave,MC2050, Chicago, IL 60637 USA.
EM hkenny@uchicago.edu; elengyel@uchicago.edu
FU charitable beneficiary of the Chicago Bears Football Club; National
Institute of Neurological Disorders and Stroke (NINDS) [R21 NS075702];
National Cancer Institute [R01 CA111882]; National Institutes of Health
(NIH) Common Fund Molecular Libraries and Imaging Program [U54
MH084681]; Bears Care
FX We thank Dr A.F. Haney (the University of Chicago, Department of
Obstetrics and Gynecology) for collecting all omental biopsies and G.
Isenberg (the University of Chicago) for carefully editing the
manuscript. We also thank the Cellular Screening Center core facility at
the University of Chicago as well as the automation and compound
management team at the National Center for Advancing Translational
Sciences (NCATS) for their expert technical support. Finally, we thank
all the patients, residents and attending physicians in the Department
of Obstetrics and Gynecology at the University of Chicago for their
commitment to collecting tissues for these experiments. This work was
supported by Bears Care, the charitable beneficiary of the Chicago Bears
Football Club, the National Institute of Neurological Disorders and
Stroke (NINDS) R21 NS075702, the National Cancer Institute grant R01
CA111882 to E.L. and by the National Institutes of Health (NIH) Common
Fund Molecular Libraries and Imaging Program Grant U54 MH084681 to
NCATS.
NR 35
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U1 3
U2 19
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 FEB
PY 2015
VL 6
AR 6220
DI 10.1038/ncomms7220
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CC2UW
UT WOS:000350201100029
PM 25653139
ER
PT J
AU Mishra, A
Brown, AL
Yao, XL
Yang, ST
Park, SJ
Liu, CY
Dagur, PK
McCoy, JP
Keeran, KJ
Nugent, GZ
Jeffries, KR
Qu, X
Yu, ZX
Levine, SJ
Chung, JH
AF Mishra, Amarjit
Brown, Alexandra L.
Yao, Xianglan
Yang, Shutong
Park, Sung-Jun
Liu, Chengyu
Dagur, Pradeep K.
McCoy, J. Philip
Keeran, Karen J.
Nugent, Gayle Z.
Jeffries, Kenneth R.
Qu, Xuan
Yu, Zu-Xi
Levine, Stewart J.
Chung, Jay H.
TI Dendritic cells induce Th2-mediated airway inflammatory responses to
house dust mite via DNA-dependent protein kinase
SO NATURE COMMUNICATIONS
LA English
DT Article
ID SEVERE COMBINED IMMUNODEFICIENCY; CATALYTIC SUBUNIT; T-CELLS; ANTIGEN
PRESENTATION; OXIDATIVE STRESS; V(D)J RECOMBINATION; INHIBITOR NU7441;
POTENTIAL ROLE; SCID MICE; IN-VIVO
AB DNA-dependent protein kinase (DNA-PK) mediates double-stranded DNA break repair, V(D)J recombination and immunoglobulin class switch recombination, as well as innate immune and pro-inflammatory responses. However, there is limited information regarding the role of DNA-PK in adaptive immunity mediated by dendritic cells (DCs), which are the primary antigen-presenting cells in allergic asthma. Here we show that house dust mite induces DNA-PK phosphorylation, which is a marker of DNA-PK activation, in DCs via the generation of intracellular reactive oxygen species. We also demonstrate that pharmacological inhibition of DNA-PK, as well as the specific deletion of DNA-PK in DCs, attenuates the induction of allergic sensitization and Th2 immunity via a mechanism that involves the impaired presentation of mite antigens. Furthermore, pharmacological inhibition of DNA-PK following antigen priming similarly reduces the manifestations of mite-induced airway disease. Collectively, these findings suggest that DNA-PK may be a potential target for treatment of allergic asthma.
C1 [Mishra, Amarjit; Yao, Xianglan; Levine, Stewart J.] NHLBI, Lab Asthma & Lung Inflammat, Div Intramural Res, NIH, Bethesda, MD 20892 USA.
[Brown, Alexandra L.; Yang, Shutong; Park, Sung-Jun; Chung, Jay H.] NHLBI, Lab Obes & Aging Res, Div Intramural Res, NIH, Bethesda, MD 20892 USA.
[Liu, Chengyu] NHLBI, Transgen Core Facil, Div Intramural Res, NIH, Bethesda, MD 20892 USA.
[Dagur, Pradeep K.; McCoy, J. Philip] NHLBI, Flow Cytometry Core Facil, Div Intramural Res, NIH, Bethesda, MD 20892 USA.
[Keeran, Karen J.; Nugent, Gayle Z.; Jeffries, Kenneth R.] NHLBI, Anim Surg & Resources Core Facil, Div Intramural Res, NIH, Bethesda, MD 20892 USA.
[Qu, Xuan; Yu, Zu-Xi] NHLBI, Pathol Core Facil, Div Intramural Res, NIH, Bethesda, MD 20892 USA.
RP Levine, SJ (reprint author), NHLBI, Lab Asthma & Lung Inflammat, Div Intramural Res, NIH, Bethesda, MD 20892 USA.
EM levines@nhlbi.nih.gov; chungj@nhlbi.nih.gov
RI MISHRA, AMARJIT/D-7504-2016
OI MISHRA, AMARJIT/0000-0002-3777-0338
FU Division of Intramural Research, National Heart, Lung, and Blood
Institute
FX We thank Dalton Saunders for his assistance with mouse management. We
also thank Dr Martha Vaughan and Dr Joel Moss for their helpful
discussions. This study was supported by the Division of Intramural
Research, National Heart, Lung, and Blood Institute.
NR 63
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U1 2
U2 15
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 FEB
PY 2015
VL 6
AR 6224
DI 10.1038/ncomms7224
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CC2UW
UT WOS:000350201100033
PM 25692509
ER
PT J
AU Mooshagian, E
Keisler, A
Zimmermann, T
Schweickert, JM
Wassermann, EM
AF Mooshagian, Eric
Keisler, Aysha
Zimmermann, Trelawny
Schweickert, Janell M.
Wassermann, Eric M.
TI Modulation of corticospinal excitability by reward depends on task
framing
SO NEUROPSYCHOLOGIA
LA English
DT Article
DE Uncertainty; Expectation; Reward probability; Transcranial magnetic
stimulation; Corticospinal excitability
ID PRIMARY MOTOR CORTEX; TRANSCRANIAL MAGNETIC STIMULATION; DOPAMINE
NEURONS; REACTION-TIME; MIDBRAIN DOPAMINE; IMPLICIT; UNCERTAINTY;
PLASTICITY; SIGNALS; INFORMATION
AB Findings from previous transcranial magnetic stimulation (TMS) experiments suggest that the primary motor cortex (M1) is sensitive to reward conditions in the environment. However, the nature of this influence on M1 activity is poorly understood. The dopamine neuron response to conditioned stimuli encodes reward probability and outcome uncertainty, or the extent to which the outcome of a situation is known. Reward uncertainty and probability are related: uncertainty is maximal when probability is 0.5 and minimal when probability is 0 or 1 (i.e., certain outcome). Previous TMS-reward studies did not examine these factors independently. Here, we used single-pulse TMS to measure corticospinal excitability in 40 individuals while they performed a simple computer task, making guesses to find or avoid a hidden target. The task stimuli implied three levels of reward probability and two levels of uncertainty. We found that reward probability level interacted with the trial search condition. That is, motor evoked potential (MEP) amplitude, a measure of corticospinal neuron excitability, increased with increasing reward probability when participants were instructed to "find" a target, but not when they were instructed to "avoid" a target. There was no effect of uncertainty on MEPs. Response times varied with the number of choices. A subset of participants also received paired-pulse stimulation to evaluate changes in short-intracortical inhibition (SICI). No effects of SICI were observed. Taken together, the results suggest that the reward-contingent modulation of M1 activity reflects reward probability or a related aspect of utility, not outcome uncertainty, and that this effect is sensitive to the conceptual framing of the task. Published by Elsevier Ltd.
C1 [Mooshagian, Eric; Keisler, Aysha; Zimmermann, Trelawny; Wassermann, Eric M.] NINDS, Behav Neurol Unit, NIH, Bethesda, MD 20892 USA.
[Mooshagian, Eric; Keisler, Aysha; Zimmermann, Trelawny] Uniformed Serv Univ Hlth Sci, Henry M Jackson Fdn, Ctr Neurosci & Regenerat Med, Rockville, MD 20852 USA.
[Schweickert, Janell M.] Wake Kendall Grp PLLC, Washington, DC 20015 USA.
RP Wassermann, EM (reprint author), NINDS, Behav Neurol Unit, NIH, 10 CTR DR,MSC 1440, Bethesda, MD 20892 USA.
EM wassermanne@ninds.nih.gov
FU Clinical Neuroscience Program of the National Institute of Neurological
Disorders and Stroke; Center for Neuroscience and Regenerative Medicine
via the Henry M. Jackson Foundation for the Advancement of Military
Medicine
FX Support for this work included intramural funding from the Clinical
Neuroscience Program of the National Institute of Neurological Disorders
and Stroke (EW) and funding from the Center for Neuroscience and
Regenerative Medicine (AK, EM, EW, and TZ), via the Henry M. Jackson
Foundation for the Advancement of Military Medicine. The authors have no
conflicts of interest to report. The authors would like to thank Mr.
Eric Emmons for his assistance with pilot data collection.
NR 41
TC 7
Z9 7
U1 0
U2 2
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0028-3932
EI 1873-3514
J9 NEUROPSYCHOLOGIA
JI Neuropsychologia
PD FEB
PY 2015
VL 68
BP 31
EP 37
DI 10.1016/j.neuropsychologia.2014.12.021
PG 7
WC Behavioral Sciences; Neurosciences; Psychology, Experimental
SC Behavioral Sciences; Neurosciences & Neurology; Psychology
GA CC1AS
UT WOS:000350074000004
PM 25543022
ER
PT J
AU Martin, S
Schmitt, SN
Wolters, PL
Abel, B
Toledo-Tamula, MA
Baldwin, A
Wicksell, RK
Merchant, M
Widemann, B
AF Martin, Staci
Schmitt, Shawn Nelson
Wolters, Pamela L.
Abel, Brittany
Toledo-Tamula, Mary Anne
Baldwin, Andrea
Wicksell, Rikard K.
Merchant, Melinda
Widemann, Brigitte
TI Development and Validation of the English Pain Interference Index and
Pain Interference Index-Parent Report
SO PAIN MEDICINE
LA English
DT Article
DE Pain Interference; Validation; NF1; Cancer; Children; Adolescents
ID QUALITY-OF-LIFE; RANDOMIZED CONTROLLED-TRIAL; PEDIATRIC PAIN; PLEXIFORM
NEUROFIBROMAS; CANCER PAIN; CHILDREN; AGREEMENT; DISEASE; ADOLESCENTS;
STRATEGIES
AB ObjectiveMeasurement of pain interference in children is challenged by a lack of validated measures with a parent proxy report. This study investigated the psychometric properties of the Pain Interference Index (PII), a six-item questionnaire originally developed in Swedish, in chronically ill youth.
MethodsWe adapted the PII for English-speaking participants and created a parallel parent proxy measure. Respondents indicate how much pain has interfered with the child's life in the past 2 weeks (0-6 scale); higher scores indicate more pain interference. Eligible participants included individuals 6-25 years with neurofibromatosis type 1 (NF1) and cancer. Internal consistency was assessed; validity was examined by correlating PII scores with existing measures of pain interference (Modified Brief Pain Inventory [MBPI]) and pain intensity (visual analogue scale [VAS]), and with measures of disease severity.
ResultsAmong 60 participants (mean age 14.7 years, range 6-24) and their parents, PII internal consistency was 0.84 and 0.96, respectively. PII scores correlated with MBPI (r=0.81, P<0.0001) and VAS (r=0.55, P<0.0001) scores and differentiated between patients with mild vs moderate/severe NF1 disease severity (P<0.05). The PII-Parent was significantly correlated with the mothers' and fathers' VAS rating of the child's pain intensity (Ps<0.01).
ConclusionsInternal consistency of the English PII is high; validity is supported by the PII's correlations with other measures of pain interference and pain intensity, and with disease severity in patients with NF1. Preliminary data indicate that the English PII is a reliable, valid, feasible pain interference measure for youth with NF1 and cancer.
C1 [Martin, Staci; Wolters, Pamela L.; Abel, Brittany; Baldwin, Andrea; Merchant, Melinda; Widemann, Brigitte] NCI, NIH, Bethesda, MD 20892 USA.
[Schmitt, Shawn Nelson] Uniformed Serv Univ Hlth Sci, Ettenhofer Lab Neurocognit Res, Bethesda, MD 20814 USA.
[Toledo-Tamula, Mary Anne] Leidos Biomed Labs, Natl Lab Canc Res, Frederick, MD USA.
[Wicksell, Rikard K.] Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden.
[Wicksell, Rikard K.] Karolinska Univ Hosp, Behav Med Pain Treatment Serv, Stockholm, Sweden.
RP Martin, S (reprint author), NCI, Hlth Psychol & Neurobehav Res Grp, 9030 Old Georgetown Rd,107, Bethesda, MD 20892 USA.
EM martins@mail.nih.gov
FU Intramural Research Program of the National Institutes of Health,
National Cancer Institute; National Cancer Institute, National
Institutes of Health [HHSN261200800001E]
FX The authors are grateful to the patients and families who participated
in this study. We also thank Amy Starosta, MA, Katherine Burns, PhD, and
Ethan Eisen, M.Phil, for their assistance with data collection. This
research was supported by the Intramural Research Program of the
National Institutes of Health, National Cancer Institute. In addition,
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.
NR 40
TC 7
Z9 7
U1 1
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1526-2375
EI 1526-4637
J9 PAIN MED
JI Pain Med.
PD FEB
PY 2015
VL 16
IS 2
BP 367
EP 373
DI 10.1111/pme.12620
PG 7
WC Medicine, General & Internal
SC General & Internal Medicine
GA CB9UU
UT WOS:000349979600021
PM 25377441
ER
PT J
AU Alvarez-Hernandez, G
Murillo-Benitez, C
Candia-Plata, MD
Moro, M
AF Alvarez-Hernandez, Gerardo
Murillo-Benitez, Coral
del Carmen Candia-Plata, Maria
Moro, Manuel
TI Clinical Profile and Predictors of Fatal Rocky Mountain Spotted Fever in
Children from Sonora, Mexico
SO PEDIATRIC INFECTIOUS DISEASE JOURNAL
LA English
DT Article
DE Rocky Mountain spotted fever; children; Mexico
ID ACUTE-RENAL-FAILURE; UNITED-STATES; RISK-FACTORS; SOUTHEASTERN BRAZIL;
SURVEILLANCE; MORTALITY; FEATURES
AB Background: Rocky Mountain spotted fever (RMSF) is an increasingly important cause of preventable mortality in children in Sonora, Mexico. Although early treatment with tetracycline has shown to prevent fatal outcome, the disease remains a life-threatening condition, particularly for children. This study describes the clinical factors associated with pediatric mortality due to RMSF in Sonora, in order to guide healthcare practices.
Methods: This is a retrospective analysis of 104 children consecutively hospitalized at the major pediatric hospital of Sonora, diagnosed with RMSF between January 2004 and December 2013. Descriptive statistics and multiple logistic regression were used to identify risk factors for fatal outcome.
Results: The case fatality ratio in this cohort was 20.2%. Children were hospitalized after a median of 6 days from onset of symptoms including fever (100%), rash involving palms and soles (88.5%) and headache (79.8%); 90.4% of fatal cases had low platelet counts (<50,000/mu L) and 33.3% showed serum creatinine concentrations above the normal value. Acute kidney injury increased mortality, odds ratio (ORadj) = 4.84, 95% confidence interval (CI): 1.2-16.2, as well as delay in treatment (>= 5th day from onset) with doxycycline, ORadj = 2.62, 95% CI: 1.24-5.52 and hemorrhage, ORadj = 6.11, 95% CI: 1.89-19.69.
Conclusions: RMSF is a public health problem in Sonora. Clinically, fatal cases differ from non-fatal cases in renal function and hemorrhagic manifestations, although these findings may occur too late for a timely intervention. First-line providers must be educated to harbor a timely suspicion of RMSF, and should provide empiric treatment with doxycycline when febrile patients first present for care.
C1 [Alvarez-Hernandez, Gerardo; del Carmen Candia-Plata, Maria] Univ Sonora, Dept Med & Hlth Sci, Hermosillo 83000, Sonora, Mexico.
[Murillo-Benitez, Coral] Inst Tecnol & Estudios Super Monterrey, Sch Med & Hlth Sci, Monterrey, Mexico.
[Moro, Manuel] NIH, Div Comparat Med, Off Res Infrastruct Programs, Bethesda, MD 20892 USA.
RP Alvarez-Hernandez, G (reprint author), Univ Sonora, Dept Med & Hlth Sci, Blvd Luis D Colosio SN, Hermosillo 83000, Sonora, Mexico.
EM galvarez@guayacan.uson.mx
FU Sonora State Children's Hospital of Mexico's Ministry of Public Health
FX The authors thank the support of the Sonora State Children's Hospital of
Mexico's Ministry of Public Health for the completion of this study. The
authors also thank Dr. Jennifer McQuiston for the valuable comments made
to this article.
NR 29
TC 6
Z9 6
U1 1
U2 9
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0891-3668
EI 1532-0987
J9 PEDIATR INFECT DIS J
JI Pediatr. Infect. Dis. J.
PD FEB
PY 2015
VL 34
IS 2
BP 125
EP 130
DI 10.1097/INF.0000000000000496
PG 6
WC Immunology; Infectious Diseases; Pediatrics
SC Immunology; Infectious Diseases; Pediatrics
GA CB8VE
UT WOS:000349908800005
PM 25126856
ER
PT J
AU Rutstein, RM
Samson, P
Fenton, T
Fletcher, CV
Kiser, JJ
Mofenson, LM
Smith, E
Graham, B
Mathew, M
Aldrovani, G
AF Rutstein, Richard M.
Samson, Pearl
Fenton, Terry
Fletcher, Courtney V.
Kiser, Jennifer J.
Mofenson, Lynne M.
Smith, Elizabeth
Graham, Bobbie
Mathew, Marina
Aldrovani, Grace
CA PACTG 1020A Study Team
TI Long-term Safety and Efficacy of Atazanavir-based Therapy in
HIV-infected Infants, Children and Adolescents The Pediatric AIDS
Clinical Trials Group Protocol 1020A
SO PEDIATRIC INFECTIOUS DISEASE JOURNAL
LA English
DT Article
DE atazanavir; pediatric HIV; antiretroviral treatment
ID ACTIVE ANTIRETROVIRAL THERAPY; TWICE-DAILY LOPINAVIR/RITONAVIR;
ONCE-DAILY ATAZANAVIR/RITONAVIR; INCLUDING PROTEASE INHIBITORS; MULTIPLE
VIROLOGICAL FAILURES; NAIVE HIV-1-INFECTED PATIENTS; MORTALITY-RATES;
YOUNG-ADULTS; RITONAVIR; PHARMACOKINETICS
AB Background: Atazanavir (ATV) is an attractive option for the treatment of Pediatric HIV infection, based on once-daily dosing and the availability of a formulation appropriate for younger children. Pediatric AIDS Clinical Trials Group 1020A was a phase I/II open label study of ATV (with/without ritonavir [RTV] boosting)-based treatment of HIV-infected children; here we report the long-term safety and virologic and immunologic responses.
Methods: Antiretroviral-naive and experienced children, ages 91 days to 21 years, with baseline plasma HIV RNA > 5000 copies/mL (cpm) were enrolled at sites in the United States and South Africa.
Results: Of 195 children enrolled, 142 (73%) subjects received ATV-based regimens at the final protocol recommended dose; 58% were treatment naive. Overall, at week 24, 84/139 subjects (60.4%) and at week 48, 83/142 (58.5%) had HIV RNA <= 400 cpm. At week 48, 69.5% of naive and 43.3% of experienced subjects had HIV RNA <= 400 cpm; median CD4 increase was 196.5 cells/mm(3). The primary adverse event (AE) was increased serum bilirubin; 9% of subjects had levels >= 5.1 times upper limit of normal (ULN) and 1.4% noted jaundice. Three percent of subjects experienced grade 2 or 3 prolongation in PR or QTc intervals. At week 48, there was a 15% increase in total cholesterol (TC), with TC > 199 mg/dL increasing from 1% at baseline to 5.7%.
Conclusions: Use of once-daily ATV, with/without RTV, was safe and well tolerated in children, with acceptable levels of viral suppression and CD4 count increase. The primary AE, as expected, was an increase in bilirubin levels.
C1 [Rutstein, Richard M.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
[Samson, Pearl; Fenton, Terry] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
[Fletcher, Courtney V.] Univ Nebraska Med Ctr, Omaha, NE USA.
[Kiser, Jennifer J.] Univ Colorado, Hlth Sci Ctr, Aurora, CO USA.
[Mofenson, Lynne M.] NIAID, Div Aids, NIH, Bethesda, MD 20892 USA.
[Smith, Elizabeth] NICHD, Maternal & Pediat Infect Dis Branch, NIH, Bethesda, MD USA.
[Graham, Bobbie] Frontier Sci Technol Res Fdn, Amherst, NY USA.
[Mathew, Marina] Bristol Myers Squibb Co, Wallingford, CT 06492 USA.
[Aldrovani, Grace] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA.
RP Rutstein, RM (reprint author), Childrens Hosp Philadelphia, Div Gen Pediat, Room 12NW60,Main Bldg,34th & Civ Ctr Blvd, Philadelphia, PA 19104 USA.
EM Rutstein@email.chop.edu
FU National Institute of Allergy and Infectious Diseases (NIAID) [U01
AI068632]; Eunice Kennedy Shriver National Institute of Child Health and
Human Development (NICHD); National Institute of Mental Health (NIMH)
[AI068632]; Statistical and Data Analysis Center at Harvard School of
Public Health, under the National Institute of Allergy and Infectious
Diseases [5 U01 AI41110]; Pediatric AIDS Clinical Trials Group (PACTG);
IMPAACT Group [1 U01 AI068616]; National Institute of Allergy and
Infectious Diseases (NIAID); NICHD International and Domestic Pediatric
and Maternal HIV Clinical Trials Network - NICHD
[N01-DK-9-001/HHSN267200800001C]
FX Overall support for the International Maternal Pediatric Adolescent AIDS
Clinical Trials Group (IMPAACT) was provided by the National Institute
of Allergy and Infectious Diseases (NIAID) [U01 AI068632], the Eunice
Kennedy Shriver National Institute of Child Health and Human Development
(NICHD), and the National Institute of Mental Health (NIMH) [AI068632].
The content is solely the responsibility of the authors and does not
necessarily represent the official views of the NIH. This work was
supported by the Statistical and Data Analysis Center at Harvard School
of Public Health, under the National Institute of Allergy and Infectious
Diseases cooperative agreement #5 U01 AI41110 with the Pediatric AIDS
Clinical Trials Group (PACTG) and #1 U01 AI068616 with the IMPAACT
Group. Support of the sites was provided by the National Institute of
Allergy and Infectious Diseases (NIAID) and the NICHD International and
Domestic Pediatric and Maternal HIV Clinical Trials Network funded by
NICHD (contract number N01-DK-9-001/HHSN267200800001C). Protocol support
also provided by Bristol-Myers Squibb. M Matthew is an employee of
Bristol-Myers Squibb. The authors have no other funding or conflicts of
interest to disclose.
NR 31
TC 5
Z9 5
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0891-3668
EI 1532-0987
J9 PEDIATR INFECT DIS J
JI Pediatr. Infect. Dis. J.
PD FEB
PY 2015
VL 34
IS 2
BP 162
EP 167
DI 10.1097/INF.0000000000000538
PG 6
WC Immunology; Infectious Diseases; Pediatrics
SC Immunology; Infectious Diseases; Pediatrics
GA CB8VE
UT WOS:000349908800012
PM 25232777
ER
PT J
AU Cournil, A
Van de Perre, P
Cames, C
de Vincenzi, I
Read, JS
Luchters, S
Meda, N
Naidu, K
Newell, ML
Bork, K
AF Cournil, Amandine
Van de Perre, Philippe
Cames, Cecile
de Vincenzi, Isabelle
Read, Jennifer S.
Luchters, Stanley
Meda, Nicolas
Naidu, Kevi
Newell, Marie-Louise
Bork, Kirsten
CA Kesho Bora Study Grp
TI Early Infant Feeding Patterns and HIV-free Survival Findings from the
Kesho-Bora Trial (Burkina Faso, Kenya, South Africa)
SO PEDIATRIC INFECTIOUS DISEASE JOURNAL
LA English
DT Article
DE infant; HIV-free survival; prevention of mother-to-child transmission;
breastfeeding; antiretroviral therapy; Africa
ID TO-CHILD TRANSMISSION; RANDOMIZED CONTROLLED-TRIAL; PROPENSITY SCORE
METHODS; INFECTED MOTHERS; ANTIRETROVIRAL THERAPY; UNINFECTED CHILDREN;
BREAST-MILK; ZIDOVUDINE PROPHYLAXIS; CLINICAL-TRIAL; CELL-FREE
AB Objective: To investigate the association between feeding patterns and HIV-free survival in children born to HIV-infected mothers and to clarify whether antiretroviral (ARV) prophylaxis modifies the association.
Methods: From June 2005 to August 2008, HIV-infected pregnant women were counseled regarding infant feeding options, and randomly assigned to triple-ARV prophylaxis (triple ARV) until breastfeeding cessation (BFC) before age 6 months or antenatal zidovudine with single-dose nevirapine (short-course ARV). Eighteen-month HIV-free survival of infants HIV-negative at 2 weeks of age was assessed by feeding patterns (replacement feeding from birth, BFC <3 months, BFC >= 3 months).
Results: Of the 753 infants alive and HIV-negative at 2 weeks, 28 acquired infection and 47 died by 18 months. Overall HIV-free survival at 18 months was 0.91 [95% confidence interval (CI): 0.88-0.93]. In the short-course ARV arm, HIV-free survival (0.88; CI: 0.84-0.91) did not differ by feeding patterns. In the triple ARV arm, overall HIV-free survival was 0.93 (CI: 0.90-0.95) and BFC <3 months was associated with lower HIV-free survival than BFC >= 3 months (adjusted hazard ratio: 0.36; CI: 0.15-0.83) and replacement feeding (adjusted hazard ratio: 0.20; CI: 0.04-0.94). In the triple ARV arm, 4 of 9 transmissions occurred after reported BFC (and 5 of 19 in the short-course arm), indicating that some women continued breastfeeding after interruption of ARV prophylaxis.
Conclusions: In resource-constrained settings, early weaning has previously been associated with higher infant mortality. We show that, even with maternal triple-ARV prophylaxis during breastfeeding, early weaning remains associated with lower HIV-free survival, driven in particular by increased mortality.
C1 [Cournil, Amandine; Cames, Cecile; Bork, Kirsten] UM1, IRD, UMI233, F-34394 Montpellier 5, France.
[Van de Perre, Philippe] INSERM, Dept Bacteriol Virol, U1058, Montpellier, France.
[Van de Perre, Philippe] Univ Montpellier, F-34059 Montpellier, France.
[Van de Perre, Philippe] CHRU Montpellier, Montpellier, France.
[de Vincenzi, Isabelle] WHO, Dept Reprod Hlth & Res, CH-1211 Geneva, Switzerland.
[Read, Jennifer S.] NIH, Bethesda, MD 20892 USA.
[Luchters, Stanley] ICRH, Mombasa, Kenya.
[Luchters, Stanley] Univ Ghent, Int Ctr Reprod Hlth, B-9000 Ghent, Belgium.
[Meda, Nicolas] Ctr Muraz, Bobo Dioulasso, Burkina Faso.
[Naidu, Kevi] Univ KwaZulu Natal, Durban, South Africa.
[Newell, Marie-Louise] Univ KwaZulu Natal, Africa Ctr Hlth & Populat Studies, Somkhele, South Africa.
RP Cournil, A (reprint author), UM1, IRD, UMI233, BP 64501, F-34394 Montpellier 5, France.
EM amandine.cournil@ird.fr
RI Van de Perre, Philippe/B-9692-2008;
OI Van de Perre, Philippe/0000-0002-3912-0427; Newell,
Marie-Louise/0000-0002-1074-7699; Bork, Kirsten/0000-0002-5909-7332;
Njagi, Ephantus/0000-0002-1484-0241
FU Agence Nationale de Recherche sur le SIDA et les hepatites virales
(ANRS); Department for International Development (DFID); European and
Developing Countries Clinical Trials Partnership (EDCTP); Thrasher
Research Fund; Belgian Directorate General for International
Cooperation; GlaxoSmithKline Foundation; Centers for Disease Control and
Prevention; Eunice Kennedy Shriver National Institute of Child Health
and Human Development; UNDP/UNFPA/UNICEF/World Bank/WHO Special
Programme of Research, Development and Research Training in Human
Reproduction; Victorian Operational Infrastructure Support Program
FX Financial support was provided by Agence Nationale de Recherche sur le
SIDA et les hepatites virales (ANRS), Department for International
Development (DFID), European and Developing Countries Clinical Trials
Partnership (EDCTP), Thrasher Research Fund, Belgian Directorate General
for International Cooperation, GlaxoSmithKline Foundation, Centers for
Disease Control and Prevention, Eunice Kennedy Shriver National
Institute of Child Health and Human Development, UNDP/UNFPA/UNICEF/World
Bank/WHO Special Programme of Research, Development and Research
Training in Human Reproduction and the Victorian Operational
Infrastructure Support Program. The authors have no other funding or
conflicts of interest to disclose.
NR 41
TC 3
Z9 4
U1 1
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0891-3668
EI 1532-0987
J9 PEDIATR INFECT DIS J
JI Pediatr. Infect. Dis. J.
PD FEB
PY 2015
VL 34
IS 2
BP 168
EP 174
DI 10.1097/INF.0000000000000512
PG 7
WC Immunology; Infectious Diseases; Pediatrics
SC Immunology; Infectious Diseases; Pediatrics
GA CB8VE
UT WOS:000349908800013
PM 25741969
ER
PT J
AU Duarte, JO
Cruz, FC
Leao, RM
Planeta, CS
Crestani, CC
AF Duarte, Josiane O.
Cruz, Fabio C.
Leao, Rodrigo M.
Planeta, Cleopatra S.
Crestani, Carlos C.
TI Stress Vulnerability During Adolescence: Comparison of Chronic Stressors
in Adolescent and Adult Rats
SO PSYCHOSOMATIC MEDICINE
LA English
DT Article
DE unpredictable stress; restraint; autonomic; baroreflex; vascular;
glucocorticoids
ID DIFFERENTIAL CARDIOVASCULAR-RESPONSES; CORTICOTROPIN-RELEASING FACTOR;
NITRIC-OXIDE; REPEATED RESTRAINT; VENTRICULAR-ARRHYTHMIAS;
ESSENTIAL-HYPERTENSION; VASCULAR REACTIVITY; BAROREFLEX FUNCTION;
BRAIN-DEVELOPMENT; VARIABLE STRESS
AB Objective This study investigated the physiological and somatic changes evoked by daily exposure to the same type of stressor (homotypic) or different aversive stressor stimuli (heterotypic) in adolescent and adult rats, with a focus on cardiovascular function. The long-term effects of stress exposure during adolescence were also investigated longitudinally.
Methods Male Wistar rats were exposed to repeated restraint stress (RRS, homotypic) or chronic variable stress (CVS, heterotypic).
Results Adrenal hypertrophy, thymus involution, and elevated plasma glucocorticoid were observed only in adolescent animals, whereas reduction in body weight was caused by both stress regimens in adults. CVS increased mean arterial pressure (adolescent: p = .001; adult: p = .005) and heart rate (HR; adolescent: p = .020; adult: p = .011) regardless of the age, whereas RRS increased blood pressure selectively in adults (p = .001). Rest tachycardia evoked by CVS was associated with increased cardiac sympathetic activity in adults, whereas a decreased cardiac parasympathetic activity was observed in adolescent animals. Changes in cardiovascular function and cardiac autonomic activity evoked by both CVS and RRS were followed by alterations in baroreflex activity and vascular reactivity to vasoconstrictor and vasodilator agents in adolescent adult animals. Except for the circulating glucocorticoid change, all alterations observed during adolescence were reversed in adulthood.
Conclusions These findings suggest a stress vulnerability of adolescents to somatic and neuroendocrine effects regardless of stress regimen. Our results indicated an age-stress type-specific influence in stress-evoked cardiovascular/autonomic changes. Data suggest minimal consequences in adulthood of stress during adolescence.
C1 [Duarte, Josiane O.; Planeta, Cleopatra S.; Crestani, Carlos C.] Univ Estadual Paulista UNESP, Pharmacol Lab, Sch Pharmaceut Sci, Araraquara, SP, Brazil.
[Duarte, Josiane O.; Planeta, Cleopatra S.; Crestani, Carlos C.] Joint UFSCar UNESP Grad Program Physiol Sci, Sao Carlos, SP, Brazil.
[Cruz, Fabio C.; Leao, Rodrigo M.] NIDA, Behav Neurosci Branch, Intramural Res Program, US Natl Inst Hlth,Dept Hlth & Human Serv, Baltimore, MD USA.
RP Crestani, CC (reprint author), Sao Paulo State Univ UNESP, Pharmacol Lab, Dept Nat Act Principles & Toxicol, Sch Pharmaceut Sci, Rodovia Araraquara Jau Km 01 Campus Univ, BR-14801902 Araraquara, SP, Brazil.
EM cccrestani@yahoo.com.br
RI Crestani, Carlos/E-4161-2012
FU FAPESP [2012/14376-0, 2012/50549-6]; PADC-FCF UNESP
FX This work was supported by FAPESP Grants 2012/14376-0 and 2012/50549-6
and PADC-FCF UNESP. C.S.P. is a CNPq research fellow. The authors
declare no conflicts of interest.
NR 60
TC 4
Z9 4
U1 0
U2 8
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0033-3174
EI 1534-7796
J9 PSYCHOSOM MED
JI Psychosom. Med.
PD FEB-MAR
PY 2015
VL 77
IS 2
BP 186
EP 199
DI 10.1097/PSY.0000000000000141
PG 14
WC Psychiatry; Psychology; Psychology, Multidisciplinary
SC Psychiatry; Psychology
GA CC0UC
UT WOS:000350051500009
PM 25659080
ER
PT J
AU Anthis, NJ
Clore, GM
AF Anthis, Nicholas J.
Clore, G. Marius
TI Visualizing transient dark states by NMR spectroscopy
SO QUARTERLY REVIEWS OF BIOPHYSICS
LA English
DT Review
ID PARAMAGNETIC RELAXATION ENHANCEMENT; NUCLEAR-MAGNETIC-RESONANCE;
SITE-DIRECTED SPIN; EXCITED PROTEIN STATES; LONG-RANGE STRUCTURE;
MOLECULAR-WEIGHT PROTEINS; NITROXIDE SIDE-CHAIN; MODEL-FREE APPROACH;
X-RAY-SCATTERING; DIHYDROFOLATE-REDUCTASE CATALYSIS
AB Myriad biological processes proceed through states that defy characterization by conventional atomic-resolution structural biological methods. The invisibility of these 'dark' states can arise from their transient nature, low equilibrium population, large molecular weight, and/or heterogeneity. Although they are invisible, these dark states underlie a range of processes, acting as encounter complexes between proteins and as intermediates in protein folding and aggregation. New methods have made these states accessible to high-resolution analysis by nuclear magnetic resonance (NMR) spectroscopy, as long as the dark state is in dynamic equilibrium with an NMR-visible species. These methods - paramagnetic NMR, relaxation dispersion, saturation transfer, lifetime line broadening, and hydrogen exchange - allow the exploration of otherwise invisible states in exchange with a visible species over a range of timescales, each taking advantage of some unique property of the dark state to amplify its effect on a particular NMR observable. In this review, we introduce these methods and explore two specific techniques - paramagnetic relaxation enhancement and dark state exchange saturation transfer - in greater detail.
C1 [Anthis, Nicholas J.; Clore, G. Marius] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
RP Clore, GM (reprint author), NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
EM mariusc@intra.niddk.nih.gov
FU Intramural Program of the NIH; NIDDK; Intramural AIDS Targeted Antiviral
Program of the Office of the Director of the NIH
FX We thank Nicolas Fawzi, Dennis Torchia, Vitali Tugarinov, Vincenzo
Venditti and Jinfa Ying for useful discussions and other assistance.
This work was supported by the Intramural Program of the NIH, NIDDK, and
the Intramural AIDS Targeted Antiviral Program of the Office of the
Director of the NIH (to G.M.C.).
NR 369
TC 23
Z9 23
U1 11
U2 66
PU CAMBRIDGE UNIV PRESS
PI NEW YORK
PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA
SN 0033-5835
EI 1469-8994
J9 Q REV BIOPHYS
JI Q. Rev. Biophys.
PD FEB
PY 2015
VL 48
IS 1
BP 35
EP 116
DI 10.1017/S0033583514000122
PG 82
WC Biophysics
SC Biophysics
GA CC4ES
UT WOS:000350304300002
PM 25710841
ER
PT J
AU Land, CE
Kwon, D
Hoffman, FO
Moroz, B
Drozdovitch, V
Bouville, A
Beck, H
Luckyanov, N
Weinstock, RM
Simon, SL
AF Land, Charles E.
Kwon, Deukwoo
Hoffman, F. Owen
Moroz, Brian
Drozdovitch, Vladimir
Bouville, Andre
Beck, Harold
Luckyanov, Nicholas
Weinstock, Robert M.
Simon, Steven L.
TI Accounting for Shared and Unshared Dosimetric Uncertainties in the Dose
Response for Ultrasound-Detected Thyroid Nodules after Exposure to
Radioactive Fallout
SO RADIATION RESEARCH
LA English
DT Article
ID NUCLEAR TEST-SITE; NEVADA TEST-SITE; WEAPONS TEST-SITE; LOCAL FALLOUT;
RADIATION-EXPOSURE; KAZAKSTAN; TESTS; CANCER; COHORT; METHODOLOGY
AB Dosimetic uncertainties, particularly those that are shared among subgroups of a study population, can bias, distort or reduce the slope or significance of a dose response. Exposure estimates in studies of health risks from environmental radiation exposures are generally highly uncertain and thus, susceptible to these methodological limitations. An analysis was published in 2008 concerning radiation-related thyroid nodule prevalence in a study population of 2,994 villagers under the age of 21 years old between August 1949 and September 1962 and who lived downwind from the Semipalatinsk Nuclear Test Site in Kazakhstan. This dose-response analysis identified a statistically significant association between thyroid nodule prevalence and reconstructed doses of fallout-related internal and external radiation to the thyroid gland; however, the effects of dosimetric uncertainty were not evaluated since the doses were simple point "best estimates''. In this work, we revised the 2008 study by a comprehensive treatment of dosimetric uncertainties. Our present analysis improves upon the previous study, specifically by accounting for shared and unshared uncertainties in dose estimation and risk analysis, and differs from the 2008 analysis in the following ways: 1. The study population size was reduced from 2,994 to 2,376 subjects, removing 618 persons with uncertain residence histories; 2. Simulation of multiple population dose sets (vectors) was performed using a two-dimensional Monte Carlo dose estimation method; and 3. A Bayesian model averaging approach was employed for evaluating the dose response, explicitly accounting for large and complex uncertainty in dose estimation. The results were compared against conventional regression techniques. The Bayesian approach utilizes 5,000 independent realizations of population dose vectors, each of which corresponds to a set of conditional individual median internal and external doses for the 2,376 subjects. These 5,000 population dose vectors reflect uncertainties in dosimetric parameters, partly shared and partly independent, among individual members of the study population. Risk estimates for thyroid nodules from internal irradiation were higher than those published in 2008, which results, to the best of our knowledge, from explicitly accounting for dose uncertainty. In contrast to earlier findings, the use of Bayesian methods led to the conclusion that the biological effectiveness for internal and external dose was similar. Estimates of excess relative risk per unit dose (ERR/Gy) for males (177 thyroid nodule cases) were almost 30 times those for females (571 cases) and were similar to those reported for thyroid cancers related to childhood exposures to external and internal sources in other studies. For confirmed cases of papillary thyroid cancers (3 in males, 18 in females), the ERR/Gy was also comparable to risk estimates from other studies, but not significantly different from zero. These findings represent the first reported dose response for a radiation epidemiologic study considering all known sources of shared and unshared errors in dose estimation and using a Bayesian model averaging (BMA) method for analysis of the dose response. (C) 2015 by Radiation Research Society
C1 [Land, Charles E.; Moroz, Brian; Drozdovitch, Vladimir; Bouville, Andre; Luckyanov, Nicholas; Simon, Steven L.] Natl Canc Inst, Bethesda, MD 20892 USA.
[Kwon, Deukwoo] Univ Miami, Sylvester Comprehens Canc Ctr, Miami, FL USA.
[Hoffman, F. Owen] Oak Ridge Ctr Risk Anal, Oak Ridge, TN USA.
RP Simon, SL (reprint author), NCI, Div Canc Epidemiol & Genet, 9609 Med Ctr Dr, Bethesda, MD 20892 USA.
EM ssimon@mail.nih.gov
FU National Cancer Institute Intramural Research Program; National
Institute of Allergy and Infectious Diseases [Y2-Al-5077]; National
Cancer Institute, NIAID [Y2-Al-5077]; NCI [Y3-CO-5117]
FX This work was supported by the National Cancer Institute Intramural
Research Program and by the Intra-Agency agreement between the National
Institute of Allergy and Infectious Diseases and the National Cancer
Institute, NIAID agreement Y2-Al-5077 and NCI agreement Y3-CO-5117. The
authors express appreciation to numerous colleagues who have, over the
years, participated in discussions, workshops and various analyses
related to dose estimation for radioactive fallout in Kazakhstan, in
particular, Drs. Konstantin Gordeev (deceased), Sergey Shinkarev, Lynn
Anspaugh, Boris Gusev, Zhanat Carr, Zhaxybay Zhumadilov, Masaharu Hoshi.
In addition, the authors gratefully acknowledge the efforts of those
whose work in risk analysis and uncertainty have preceded us and made
our work easier, including Drs. Ethel Gilbert, Eduard Hofer, Don Pierce,
Dale Preston, Dan Stram and Elisabeth Cardis.
NR 42
TC 4
Z9 4
U1 1
U2 11
PU RADIATION RESEARCH SOC
PI LAWRENCE
PA 810 E TENTH STREET, LAWRENCE, KS 66044 USA
SN 0033-7587
EI 1938-5404
J9 RADIAT RES
JI Radiat. Res.
PD FEB
PY 2015
VL 183
IS 2
BP 159
EP 173
DI 10.1667/RR13794.1
PG 15
WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging
SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology,
Nuclear Medicine & Medical Imaging
GA CC0KL
UT WOS:000350024200003
PM 25574587
ER
PT J
AU Groffen, DAI
Bosma, H
Koster, A
von Bonsdorff, MB
Aspelund, T
Eiriksdottir, G
Penninx, BWJH
Kempen, GIJM
Kirschbaum, C
Gudnason, V
Harris, TB
AF Groffen, Danielle A. I.
Bosma, Hans
Koster, Annemarie
von Bonsdorff, Mikaela B.
Aspelund, Thor
Eiriksdottir, Gudny
Penninx, Brenda W. J. H.
Kempen, Gertrudis I. J. M.
Kirschbaum, Clemens
Gudnason, Vilmundur
Harris, Tamara B.
TI A blunted diurnal cortisol response in the lower educated does not
explain educational differences in coronary heart disease: Findings from
the AGES-Reykjavik Study
SO SOCIAL SCIENCE & MEDICINE
LA English
DT Article
DE Iceland; Educational attainment; Salivary cortisol; Coronary heart
disease; Old age; Stress response
ID OF-THE-LITERATURE; SALIVARY CORTISOL; SOCIOECONOMIC-STATUS;
CARDIOVASCULAR-DISEASE; OLDER PERSONS; SOCIAL INEQUALITIES; ALLOSTATIC
LOAD; WHITEHALL-II; RISK-FACTORS; STRESS
AB Lower educational attainment generally is a strong predictor of coronary heart disease (CHD). The underlying mechanisms of this effect are, however, less clear. One hypothesis is that stress related to limitations imposed by lower socioeconomic status elicits changes in hypothalamic-pituitary-adrenal axis functioning, which, in turn, increases risk of CHD. In a large cohort study, we examined whether educational attainment was related to risk of fatal and non-fatal CHD and the extent to which salivary cortisol mediated this relation independent of potential confounders, including lifestyles. Data came from 3723 participants aged 66 through 96 from the Age, Gene/Environment Susceptibility (AGES) Reykjavik Study. Between 2002 and 2006, data were collected using questionnaires and examinations including morning and evening salivary samples. Hospital admission records and cause of death registries (ICD-9 and ICD-10 codes) were available until December 2009. Linear regression and Cox proportional hazards analyses were performed. Even after adjustment for potential confounders, including lifestyle, persons with lower educational attainment showed a blunted cortisol response and also greater risk of incident CHD. However, our data did not support the role of cortisol as a mediator in the association between education and CHD in an older sample (192). (C) 2014 Elsevier Ltd. All rights reserved.
C1 [Groffen, Danielle A. I.; Bosma, Hans; Koster, Annemarie] Maastricht Univ, CAPHRI Sch Publ Hlth & Primary Care, Dept Social Med, NL-6200 MD Maastricht, Netherlands.
[von Bonsdorff, Mikaela B.] Univ Jyvaskyla, Dept Hlth Sci, Gerontol Res Ctr, Jyvaskyla, Finland.
[Aspelund, Thor; Eiriksdottir, Gudny; Gudnason, Vilmundur] Iceland Heart Assoc, Kopavogur, Iceland.
[Aspelund, Thor] Univ Iceland, Fac Med, Reykjavik, Iceland.
[Penninx, Brenda W. J. H.] Vrije Univ Amsterdam Med Ctr, EMGO Inst Hlth & Care Res, Dept Psychiat, Amsterdam, Netherlands.
[Kempen, Gertrudis I. J. M.] Maastricht Univ, CAPHRI Sch Publ Hlth & Primary Care, Dept Hlth Serv Res, NL-6200 MD Maastricht, Netherlands.
[Kirschbaum, Clemens] Tech Univ Dresden, D-01062 Dresden, Germany.
[Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD 20892 USA.
RP Groffen, DAI (reprint author), Maastricht Univ, CAPHRI Sch Publ Hlth & Primary Care, Dept Social Med, POB 616, NL-6200 MD Maastricht, Netherlands.
EM D.Groffen@maastrichtuniversity.nl
RI Gudnason, Vilmundur/K-6885-2015; Aspelund, Thor/C-5983-2008; Kempen,
Gertrudis/H-5978-2016; Bosma, Hans/A-6184-2013; Koster,
Annemarie/E-7438-2010
OI Gudnason, Vilmundur/0000-0001-5696-0084; Aspelund,
Thor/0000-0002-7998-5433; Kempen, Gertrudis/0000-0002-7053-2198;
FU NIH [N01-AG-12100]; NIA Intramural Research Program, Hjartavernd (the
Icelandic Heart Association); Althingi (the Icelandic Parliament)
FX The Age, Gene/Environment Susceptibility Reykjavik Study is funded by
NIH contract N01-AG-12100, the NIA Intramural Research Program,
Hjartavernd (the Icelandic Heart Association), and The Althingi (the
Icelandic Parliament).
NR 48
TC 2
Z9 2
U1 0
U2 3
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0277-9536
J9 SOC SCI MED
JI Soc. Sci. Med.
PD FEB
PY 2015
VL 127
SI SI
BP 143
EP 149
DI 10.1016/j.socscimed.2014.09.050
PG 7
WC Public, Environmental & Occupational Health; Social Sciences, Biomedical
SC Public, Environmental & Occupational Health; Biomedical Social Sciences
GA CC1AZ
UT WOS:000350074800016
PM 25308232
ER
PT J
AU Spittel, ML
Riley, WT
Kaplan, RM
AF Spittel, Michael L.
Riley, William T.
Kaplan, Robert M.
TI Educational attainment and life expectancy: A perspective from the NIH
Office of Behavioral and Social Sciences Research
SO SOCIAL SCIENCE & MEDICINE
LA English
DT Article
DE NIH; BSSR; Education and health; Program
ID ADULT MORTALITY; UNITED-STATES; GRADIENT; HEALTH; RACE
AB The NIH Office of Behavioral and Social Sciences Research (OBSSR) furthers the mission of the NIH by stimulating behavioral and social sciences research throughout NIH and integrating these areas of research more fully into the NIH health research enterprise, thereby improving our understanding, treatment, and prevention of disease. OBSSR accomplishes this mission through several strategic priorities: (1) supporting the next generation of basic behavioral and social sciences research, (2) facilitating interdisciplinary research, (3) promoting a multi-level systems perspective of health and behavior, and (4) encouraging a problem-focused perspective on population health. Published by Elsevier Ltd.
C1 [Spittel, Michael L.; Riley, William T.] NIH, Off Behav & Social Sci Res, US Dept HHS, Bethesda, MD 20892 USA.
[Kaplan, Robert M.] US Dept HHS, Agcy Healthcare Res & Qual, Washington, DC USA.
RP Spittel, ML (reprint author), NIH, Off Behav & Social Sci Res, US Dept HHS, Bethesda, MD 20892 USA.
EM Michael.Spittel@nih.gov
NR 13
TC 1
Z9 1
U1 1
U2 5
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0277-9536
J9 SOC SCI MED
JI Soc. Sci. Med.
PD FEB
PY 2015
VL 127
SI SI
BP 203
EP 205
DI 10.1016/j.socscimed.2014.11.017
PG 3
WC Public, Environmental & Occupational Health; Social Sciences, Biomedical
SC Public, Environmental & Occupational Health; Biomedical Social Sciences
GA CC1AZ
UT WOS:000350074800024
PM 25511259
ER
PT J
AU Liu, R
Li, MY
Li, ZD
Hong, N
Xu, HY
Hong, YH
AF Liu, Rong
Li, Mingyou
Li, Zhendong
Hong, Ni
Xu, Hongyan
Hong, Yunhan
TI Medaka Oct4 is Essential for Pluripotency in Blastula Formation and ES
Cell Derivation
SO STEM CELL REVIEWS AND REPORTS
LA English
DT Article
DE ES cell; Germ cell; Oct4; Pou2; Pluripotency
ID EMBRYONIC STEM-CELLS; POU DOMAIN; TRANSCRIPTIONAL REGULATION;
ORYZIAS-LATIPES; ADULT GONADS; GERM-CELLS; EXPRESSION; ZEBRAFISH; FISH;
VERTEBRATE
AB The origin and evolution of molecular mechanisms underlying cellular pluripotency is a fundamental question in stem cell biology. The transcription factor Oct4 or Pou5f1 identified in mouse features pluripotency expression and activity in the inner cell mass and embryonic stem (ES) cells. Pou2 identified in zebrafish is the non-mammalian homolog prototype of mouse Oct4. The genes oct4 and pou2 have reportedly evolved by pou5 gene duplication in the common ancestor of vertebrates. Unlike mouse oct4, however, zebrafish pou2 lacks pluripotency expression and activity. Whether the presence of pluripotency expression and activity is specific for mammalian Oct4 or common to the ancestor of vertebrate Oct4 and Pou2 proteins has remained to be determined. Here we report that Oloct4, the medaka oct4/pou2, is essential for early embryogenesis and pluripotency maintenance. Oloct4 exists as a single copy gene and is orthologous to pou2 by sequence and chromosome synteny. Oloct4 expression occurs in early embryos, germ stem cells and ES cells like mouse oct4 but also in the brain and tail bud like zebrafish pou2. Importantly, OlOct4 depletion caused blastula lethality or blockage. We show that Oloct4 depletion abolishes ES cell derivation from midblastula embryos. Thus, Oloct4 has pluripotency expression and is essential for early embryogenesis and pluripotency maintenance. Our results demonstrate the conservation of pluripotency expression and activity in vertebrate Oct4 and Pou2 proteins. The finding that Oloct4 combines the features of mouse oct4 and zebrafish pou2 in expression and function suggests that Oloct4 might represent the ancestral prototype of vertebrate oct4 and pou2 genes.
C1 [Liu, Rong; Li, Mingyou; Li, Zhendong; Hong, Ni; Xu, Hongyan; Hong, Yunhan] Natl Univ Singapore, Dept Biol Sci, Singapore 117543, Singapore.
[Li, Mingyou; Hong, Yunhan] Shanghai Ocean Univ, Coll Fisheries & Life Sci, Shanghai 201306, Peoples R China.
[Hong, Ni] NIDDK, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA.
[Xu, Hongyan] Chinese Acad Fishery Sci, Key Lab Trop & Subtrop Fishery Resource Applicat, Minist Agr, Guangzhou 510380, Guangdong, Peoples R China.
RP Hong, YH (reprint author), Natl Univ Singapore, Dept Biol Sci, 14 Sci Dr 4, Singapore 117543, Singapore.
EM dbshyh@nus.edu.sg
FU National Research Foundation Singapore [NRF-CRP7-2010-03]
FX We thank J. Deng for fish breeding, Choy Mei Foong and Veronica Wong for
laboratory management. This work was supported by the National Research
Foundation Singapore (NRF-CRP7-2010-03).
NR 52
TC 12
Z9 12
U1 1
U2 11
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA
SN 1550-8943
EI 1558-6804
J9 STEM CELL REV REP
JI Stem Cell Rev. Rep.
PD FEB
PY 2015
VL 11
IS 1
BP 11
EP 23
DI 10.1007/s12015-014-9523-2
PG 13
WC Cell & Tissue Engineering; Cell Biology; Medicine, Research &
Experimental
SC Cell Biology; Research & Experimental Medicine
GA CB9NA
UT WOS:000349957200002
PM 25142379
ER
PT J
AU Jha, BS
Rao, M
Malik, N
AF Jha, Balendu Shekhar
Rao, Mahendra
Malik, Nasir
TI Motor Neuron Differentiation from Pluripotent Stem Cells and Other
Intermediate Proliferative Precursors that can be Discriminated by
Lineage Specific Reporters
SO STEM CELL REVIEWS AND REPORTS
LA English
DT Article
DE Motor neuron; Motoneuron; Neural Stem Cell; Motor neuron progenitor;
Stem cell differentiation; Neural differentiation; Neural induction;
Motor neuron differentiation
ID IN-VITRO DIFFERENTIATION; DIRECTED DIFFERENTIATION; SPINAL-CORD;
CONVERSION; EFFICIENT; MOTONEURONS; PROGENITORS; GENERATION; DERIVATION;
INDUCTION
AB We have used a four stage protocol to generate spinal motor neurons (MNs) from human embryonic stem cells (ESCs) and human induced pluripotent stem cells (iPSCs). These stages include the pluripotent stem cell (PSC) stage, neural stem cell (NSC) stage, OLIG2 expressing motor neuron precursor (MNP) stage, and HB9 expressing mature-MN stage. To optimize the differentiation protocol reporter lines marking the NSC and MNP stages were used. The NSC stage is a pro-proliferative precursor stage at which cells can be directed to differentiate to other neural types like cortical neurons also, in addition to MNs; thus, NSCs can be expanded and stored for future differentiation to different neural types thereby, shortening the differentiation interval as compared to the complete process of differentiation from ESCs or iPSCs. Additionally, we find that OLIG2 positive cells at the MNP stage can be cryopreserved and then recovered to continue the process of MN differentiation, thereby providing a highly stable and reproducible technique for bulk differentiation. MNPs were differentiated to MNs expressing the marker HB9 demonstrating that mature-MNs can be generated with this protocol.
C1 [Jha, Balendu Shekhar; Rao, Mahendra; Malik, Nasir] NIH, Lab Stem Cell Biol, Bethesda, MD 20892 USA.
RP Malik, N (reprint author), NIH, Lab Stem Cell Biol, Bldg 10, Bethesda, MD 20892 USA.
EM malikn@mail.nih.gov
OI Jha, Balendu Shekhar/0000-0002-6509-8171
FU NIH Common Fund, National Institutes of Health, Bethesda, USA
FX The work in this manuscript was funded by the NIH Common Fund, National
Institutes of Health, Bethesda, USA. The authors declare no potential
conflicts of interest.
NR 40
TC 4
Z9 4
U1 0
U2 5
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA
SN 1550-8943
EI 1558-6804
J9 STEM CELL REV REP
JI Stem Cell Rev. Rep.
PD FEB
PY 2015
VL 11
IS 1
BP 194
EP 204
DI 10.1007/s12015-014-9541-0
PG 11
WC Cell & Tissue Engineering; Cell Biology; Medicine, Research &
Experimental
SC Cell Biology; Research & Experimental Medicine
GA CB9NA
UT WOS:000349957200016
PM 25091426
ER
PT J
AU Knudsen, TB
Keller, DA
Sander, M
Carney, EW
Doerrer, NG
Eaton, DL
Fitzpatrick, SC
Hastings, KL
Mendrick, DL
Tice, RR
Watkins, PB
Whelan, M
AF Knudsen, Thomas B.
Keller, Douglas A.
Sander, Miriam
Carney, Edward W.
Doerrer, Nancy G.
Eaton, David L.
Fitzpatrick, Suzanne Compton
Hastings, Kenneth L.
Mendrick, Donna L.
Tice, Raymond R.
Watkins, Paul B.
Whelan, Maurice
TI FutureTox II: In vitro Data and In Silico Models for Predictive
Toxicology
SO TOXICOLOGICAL SCIENCES
LA English
DT Editorial Material
DE in vitro; in silico; modeling; predictive toxicology; risk assessment
ID CELL-DERIVED CARDIOMYOCYTES; ADVERSE OUTCOME PATHWAYS; RISK-ASSESSMENT;
ENVIRONMENTAL CHEMICALS; CONCEPTUAL-FRAMEWORK; 21(ST) CENTURY;
STEM-CELLS; 21ST-CENTURY; SYSTEMS; VISION
AB FutureTox II, a Society of Toxicology Contemporary Concepts in Toxicology workshop, was held in January, 2014. The meeting goals were to review and discuss the state of the science in toxicology in the context of implementing the NRC 21st century vision of predicting in vivo responses from in vitro and in silico data, and to define the goals for the future. Presentations and discussions were held on priority concerns such as predicting and modeling of metabolism, cell growth and differentiation, effects on sensitive subpopulations, and integrating data into risk assessment. Emerging trends in technologies such as stem cell-derived human cells, 3D organotypic culture models, mathematical modeling of cellular processes and morphogenesis, adverse outcome pathway development, and high-content imaging of in vivo systems were discussed. Although advances in moving towards an in vitro/in silico based risk assessment paradigm were apparent, knowledge gaps in these areas and limitations of technologies were identified. Specific recommendations were made for future directions and research needs in the areas of hepatotoxicity, cancer prediction, developmental toxicity, and regulatory toxicology.
C1 [Knudsen, Thomas B.] US EPA, Res Triangle Pk, NC 27711 USA.
[Keller, Douglas A.] Sanofi, Bridgewater, NJ 08807 USA.
[Sander, Miriam] Page One Editorial Serv, Boulder, CO 80304 USA.
[Carney, Edward W.] Dow Chem Co USA, Midland, MI 48674 USA.
[Doerrer, Nancy G.] Hlth & Environm Sci Inst, Washington, DC 20005 USA.
[Eaton, David L.] Univ Washington, Seattle, WA 98105 USA.
[Fitzpatrick, Suzanne Compton; Mendrick, Donna L.] US FDA, Silver Spring, MD 20993 USA.
[Hastings, Kenneth L.] Sanofi, Bethesda, MD 20814 USA.
[Tice, Raymond R.] NIEHS, Res Triangle Pk, NC 27709 USA.
[Watkins, Paul B.] Univ N Carolina, Chapel Hill, NC 27599 USA.
[Watkins, Paul B.] Hamner Inst, Res Triangle Pk, NC 27709 USA.
[Whelan, Maurice] European Commiss Joint Res Ctr, I-21027 Ispra, Italy.
RP Keller, DA (reprint author), Sanofi, 55C 420A,55 Corp Dr, Bridgewater, NJ 08807 USA.
EM douglas.keller@sanofi.com
OI Keller, Douglas/0000-0002-6186-2881
NR 50
TC 17
Z9 17
U1 3
U2 39
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1096-6080
EI 1096-0929
J9 TOXICOL SCI
JI Toxicol. Sci.
PD FEB
PY 2015
VL 143
IS 2
BP 256
EP 267
DI 10.1093/toxsci/kfu234
PG 12
WC Toxicology
SC Toxicology
GA CC1LK
UT WOS:000350102000004
PM 25628403
ER
PT J
AU Panch, SR
Yau, YY
Kang, EM
De Ravin, SS
Malech, HL
Leitman, SF
AF Panch, Sandhya R.
Yau, Yu Ying
Kang, Elizabeth M.
De Ravin, Suk See
Malech, Harry L.
Leitman, Susan F.
TI Mobilization characteristics and strategies to improve hematopoietic
progenitor cell mobilization and collection in patients with chronic
granulomatous disease and severe combined immunodeficiency
SO TRANSFUSION
LA English
DT Article
ID COLONY-STIMULATING FACTOR; BLOOD STEM-CELLS; TUMOR-NECROSIS-FACTOR;
GENE-THERAPY; INTERFERON-GAMMA; MARROW; CYCLOPHOSPHAMIDE; PREDICTORS;
MODULATION; EXPRESSION
AB BackgroundGranulocyte-colony-stimulating factor (G-CSF)-mobilized autologous hematopoietic progenitor cells (HPCs) may be collected by apheresis of patients with chronic granulomatous disease (CGD) and severe combined immunodeficiency (SCID) for use in gene therapy trials. CD34+ cell mobilization has not been well characterized in such patients.
Study Design and MethodsWe retrospectively evaluated CD34+ cell mobilization and collection in 73 consecutive CGD and SCID patients and in 99 age-, weight-, and G-CSF dose-matched healthy allogeneic controls.
ResultsIn subjects aged not more than 20 years, Day5 preapheresis circulating CD34+ counts were significantly lower in CGD and SCID patients than in controls; mean peak CD34+ cell counts were 58x10(6), 64x10(6), and 87x10(6)/L, respectively (p=0.01). The SCIDs had lower CD34+ collection efficiency than CGDs and controls; mean efficiencies were 40, 63, and 57%, respectively (p=0.003). In subjects aged more than 20 years, the CGDs had significantly lower CD34+ cell mobilization than controls; mean peak CD34+ cell counts were 41x10(6) and 113x10(6)/L, respectively (p<0.0001). In a multivariate analysis, lower erythrocyte sedimentation rate (ESR) at mobilization was significantly correlated with better CD34+ cell mobilization (p=0.007). In SCIDs, CD34 collection efficiency was positively correlated with higher red blood cell (RBC) indices (mean RBC volume, R-2=0.77; mean corpuscular hemoglobin [Hb], R-2=0.94; mean corpuscular Hb concentration, R-2=0.7; p<0.007) but not Hb.
ConclusionsCGD and SCID populations are characterized by significantly less robust CD34+ HPC mobilization than healthy controls. The presence of active inflammation or infection as suggested by an elevated ESR may negatively impact mobilization. Among SCIDs, markedly reduced CD34 collection efficiencies were related to iron deficiency, wherein decreased RBC size and density may impair apheresis cell separation mechanics.
C1 [Panch, Sandhya R.] NHLBI, NIH, Bethesda, MD 20892 USA.
[Yau, Yu Ying; Leitman, Susan F.] NIAID, Dept Transfus Med, Ctr Clin, NIH, Bethesda, MD 20892 USA.
[Kang, Elizabeth M.; De Ravin, Suk See; Malech, Harry L.] NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA.
RP Leitman, SF (reprint author), NIH, Blood Serv Sect, Dept Transfus Med, Bldg 10,Room 1C-711, Bethesda, MD 20854 USA.
EM sleitman@nih.gov
OI Malech, Harry/0000-0001-5874-5775
FU intramural research programs of the NIAID and the Clinical Center, NIH
FX This work was supported by the intramural research programs of the NIAID
and the Clinical Center, NIH. The authors are federal employees. There
were no nonfederal sources of support.
NR 33
TC 3
Z9 3
U1 2
U2 6
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 FEB
PY 2015
VL 55
IS 2
BP 265
EP 274
DI 10.1111/trf.12830
PG 10
WC Hematology
SC Hematology
GA CB7PX
UT WOS:000349820900008
PM 25143186
ER
PT J
AU Bacot, SM
Feldman, GM
Yamada, KM
Dhawan, S
AF Bacot, Silvia M.
Feldman, Gerald M.
Yamada, Kenneth M.
Dhawan, Subhash
TI Pathogenic prion protein fragment (PrP106-126) promotes human
immunodeficiency virus type-1 infection in peripheral blood
monocyte-derived macrophages
SO VIROLOGY
LA English
DT Article
DE Blood; HIV-1; Prion protein; Peripheral blood monocytes; Macrophages
ID CREUTZFELDT-JAKOB-DISEASE; NITRIC-OXIDE SYNTHASE; NF-KAPPA-B; HIV-1
INFECTION; VARIANT CJD; TRANSMISSION; TRANSFUSION; ACTIVATION;
LIPOCORTIN-1; EXPRESSION
AB Transfusion of blood and blood products contaminated with the pathogenic form of prion protein Prp(sc), thought to be the causative agent of variant a Creutzfeldt-Jakob disease (vCJD), may result in serious consequences in recipients with a compromised immune system, for example, as seen in HIV-1 infection. In the present study, we demonstrate that treatment of peripheral blood monocyte-derived macrophages (MDM) with PrP106-126, a synthetic domain of PrPSC that has intrinsic functional activities related to the full-length protein, markedly increased their susceptibility to HIV-1 infection, induced cytokine secretion, and enhanced their migratory behavior in response to N-formyl-L-methionyl-L-leucyl-L-phenylalanine (fMLP). Live-cell imaging of MDM cultured in the presence of PrP106-126 showed large cell clusters indicative of cellular activation. Tyrosine kinase inhibitor STI-571, protein kinase C inhibitor K252B, and cyclin-dependent kinase inhibitor olomoucine attenuated PrP106-126-induced altered MDM functions. These findings delineate a previously undefined functional role of PrP106-126-mediated host cell response in promoting HIV-1 pathogenesis. Published by Elsevier Inc.
C1 [Dhawan, Subhash] US FDA, Ctr Biol Evaluat & Res, Div Transfus Transmitted Dis, Bethesda, MD USA.
[Bacot, Silvia M.; Feldman, Gerald M.] US FDA, Ctr Drug Evaluat & Res, Div Monoclonal Antibodies, Bethesda, MD 20014 USA.
[Yamada, Kenneth M.] Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA.
RP Dhawan, S (reprint author), US FDA, Mol Virol Lab, Ctr Biol Evaluat & Res, Viral Immunol Sect, 10903 New Hampshire Ave,Bldg 52-72,Room 4306, Silver Spring, MD 20993 USA.
EM subhash.dhawan@fda.hhs.gov
FU FDA intramural research program; NIDCR intramural research program
FX We thank Dr. Viswanath Ragupathy, Dr. Xue Wang, Dr. David Asher, and Dr.
Pedro Piccardo for critical review of the manuscript. This work was
supported by FDA and NIDCR intramural research programs. The findings
and conclusions in this paper have not been formally disseminated by the
Food and Drug Administration and should not be construed to represent
any Agency determination or policy.
NR 25
TC 0
Z9 0
U1 1
U2 7
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 FEB
PY 2015
VL 476
BP 372
EP 376
DI 10.1016/j.virol.2014.11.032
PG 5
WC Virology
SC Virology
GA CB8MF
UT WOS:000349883000043
PM 25589240
ER
PT J
AU Roux, A
Muller, L
Jackson, SN
Baldwin, K
Womack, V
Pagiazitis, JG
O'Rourke, JR
Thanos, PK
Balaban, C
Schultz, JA
Volkow, ND
Woods, AS
AF Roux, Aurelie
Muller, Ludovic
Jackson, Shelley N.
Baldwin, Katherine
Womack, Virginia
Pagiazitis, John G.
O'Rourke, Joseph R.
Thanos, Panayotis K.
Balaban, Carey
Schultz, J. Albert
Volkow, Nora D.
Woods, Amina S.
TI Chronic Ethanol Consumption Profoundly Alters Regional Brain Ceramide
and Sphingomyelin Content in Rodents
SO ACS CHEMICAL NEUROSCIENCE
LA English
DT Article
DE Ceramide; sphingomyelin; lipids; alcohol; mass spectrometry imaging;
matrix-assisted laser desorption ionization; silver nanoparticles;
matrix implanted laser desorption ionization
ID NF-KAPPA-B; MASS-SPECTROMETRY; ALCOHOL-ABUSE; RAT-BRAIN; BIOLOGICAL
SAMPLES; TISSUE-SECTIONS; GRAY-MATTER; NEURODEGENERATION; INVOLVEMENT;
DRINKING
AB Ceramides (CER) are involved in alcohol-induced neuroinflammation. In a mouse model of chronic alcohol exposure, 16 CER and 18 sphingomyelin (SM) concentrations from whole brain lipid extracts were measured using electrospray mass spectrometry. All 18 CER concentrations in alcohol exposed adults increased significantly (range: 25-607%); in juveniles, 6 CER decreased (range: -9 to -37%). In contrast, only three SM decreased in adult and one increased significantly in juvenile. Next, regional identification at SO m spatial resolution from coronal sections was obtained with matrix implanted laser desorption/ionization mass spectrometry imaging (MILDI-MSI) by implanting silver nanoparticulate matrices followed by focused laser desorption. Most of the CER and SM quantified in whole brain extracts were detected in MILDI images. Coronal sections from three brain levels show qualitative regional changes in CER-SM ion intensities, as a function of group and brain region, in cortex, striatum, accumbens, habenula, and hippocampus. Highly correlated changes in certain white matter CER-SM pairs occur in regions across all groups, including the hippocampus and the lateral (but not medial) cerebellar cortex of adult mice. Our data provide the first microscale MS evidence of regional lipid intensity variations induced by alcohol.
C1 [Roux, Aurelie; Muller, Ludovic; Jackson, Shelley N.; Baldwin, Katherine; Womack, Virginia; Volkow, Nora D.; Woods, Amina S.] NIDA, Struct Biol Unit, IRP, NIH, Baltimore, MD 21224 USA.
[Muller, Ludovic; Womack, Virginia; Balaban, Carey] Univ Pittsburgh, Pittsburgh, PA 15260 USA.
[Schultz, J. Albert] Ionwerks Inc, Houston, TX 77002 USA.
[Pagiazitis, John G.; O'Rourke, Joseph R.; Thanos, Panayotis K.] SUNY Stony Brook, Dept Psychol, Behav Neuropharmacol & Neuroimaging Lab, Stony Brook, NY 11790 USA.
RP Woods, AS (reprint author), NIDA, IRP, NIH, 333 Cassell Dr, Baltimore, MD 21224 USA.
EM awoods@intra.nida.nih.gov
FU Intramural Research Program of the National Institute on Drug Abuse,
NIH; ARRA through NIDA phase II SBIR Grant [1RC3DA031431-01]
FX This research was supported by the Intramural Research Program of the
National Institute on Drug Abuse, NIH. lonwerks and the University of
Pittsburgh gratefully acknowledge ARRA support through NIDA phase II
SBIR Grant 1RC3DA031431-01.
NR 66
TC 6
Z9 6
U1 2
U2 3
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1948-7193
J9 ACS CHEM NEUROSCI
JI ACS Chem. Neurosci.
PD FEB
PY 2015
VL 6
IS 2
BP 247
EP 259
DI 10.1021/cn500174c
PG 13
WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Neurosciences
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Neurosciences
& Neurology
GA CB7NI
UT WOS:000349813700007
PM 25387107
ER
PT J
AU Ko, SU
Simonsick, EM
Ferrucci, L
AF Ko, Seung-uk
Simonsick, Eleanor M.
Ferrucci, Luigi
TI Gait energetic efficiency in older adults with and without knee pain:
results from the Baltimore Longitudinal Study of Aging
SO AGE
LA English
DT Article
DE Oxygen consumption; Knee pain; Energy efficiency in gait; Compensatory
effort
ID MECHANICAL WORK; WALKING; SPEED; COST
AB With aging, customary gait patterns change and energetic efficiency declines, but the relationship between these alterations is not well understood. If gait characteristics that develop with aging explain part of the decline in energetic efficiency that occur in most aging individuals, then efforts to modify these characteristics could delay or prevent mobility limitation. This study characterizes gait patterns in older persons with and without knee pain and tests the hypothesis that changes in gait characteristics due to knee pain are associated with increased energetic cost of walking in older adults. Study participants were 364 men and 170 women aged 60 to 96 years enrolled in the Baltimore Longitudinal Study of Aging (BLSA), of whom 86 had prevalent knee pain. Gait patterns were assessed at participant self-selected usual pace in the gait laboratory, and the energetic cost of walking was assessed by indirect calorimetry during self-selected usual pace walking over 2.5 min in a tiled corridor using a portable equipment. Participants with knee pain were less energetically efficient than those without pain (oxygen consumption 0.97 vs. 0.88 ml/(10 m . 100 kg); p=0.002) and had slower gait speed and smaller range of motion (ROM) at the hip and knee joints (p<0.05, for all). Slower gait speed and lower knee ROM in participants with knee pain and longer double support time and higher ankle ROM in participants without knee pain were associated with lower energetic efficiency (p<0.05, for all). Slower gait speed and lower knee ROM were correlates of knee pain and were found to mediate the association between age and oxygen consumption. Although knee pain is associated with a higher energetic cost of walking, gait characteristics associated with energetic efficiency differ by pain status which suggests that compensatory strategies both in the presence and absence of pain may impact gait efficiency.
C1 [Ko, Seung-uk] Chonnam Natl Univ, Dept Mech Engn, Yeosu 550749, South Korea.
[Simonsick, Eleanor M.; Ferrucci, Luigi] NIA, Translat Gerontol Branch, NIH, Baltimore, MD 21224 USA.
RP Ko, SU (reprint author), Chonnam Natl Univ, Dept Mech Engn, 50 Daehak Ro, Yeosu 550749, South Korea.
EM seunguk.ko@gmail.com
FU Intramural Research Program of the NIH; National Institute on Aging;
Chonnam National University
FX This research was supported entirely by the Intramural Research Program
of the NIH, National Institute on Aging, and Chonnam National
University. Data for these analyses were obtained from the Baltimore
Longitudinal Study of Aging, a study performed by the National Institute
on Aging.
NR 13
TC 0
Z9 0
U1 1
U2 4
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0161-9152
EI 1574-4647
J9 AGE
JI Age
PD FEB
PY 2015
VL 37
IS 1
AR 15
DI 10.1007/s11357-015-9754-4
PG 6
WC Geriatrics & Gerontology
SC Geriatrics & Gerontology
GA CB3JR
UT WOS:000349524600015
ER
PT J
AU Shimoyama, K
Kagawa, S
Ishida, M
Watanabe, S
Noma, K
Takehara, K
Tazawa, H
Hashimoto, Y
Tanabe, S
Matsuoka, J
Kobayashi, H
Fujiwara, T
AF Shimoyama, Kyoko
Kagawa, Shunsuke
Ishida, Michihiro
Watanabe, Shinichiro
Noma, Kazuhiro
Takehara, Kiyoto
Tazawa, Hiroshi
Hashimoto, Yuuri
Tanabe, Shunsuke
Matsuoka, Junji
Kobayashi, Hisataka
Fujiwara, Toshiyoshi
TI Viral transduction of the HER2-extracellular domain expands
trastuzumab-based photoimmunotherapy for HER2-negative breast cancer
cells
SO BREAST CANCER RESEARCH AND TREATMENT
LA English
DT Article
DE Photoimmunotherapy; HER2; Breast cancer; Adenovirus
ID PHOTOCHEMICAL INTERNALIZATION PCI; TUMOR NECROSIS FACTOR;
MONOCLONAL-ANTIBODY; GENE; TELOMERASE; RESISTANCE; THERAPY; HER2;
AMPLIFICATION; CHEMOTHERAPY
AB The prognosis of HER2-positive breast cancer has been improved by trastuzumab therapy, which features high specificity and limited side effects. However, trastuzumab-based therapy has shortcomings. Firstly, HER2-targeted therapy is only applicable to HER2-expressing tumors, which comprise only 20-25 % of primary breast cancers. Secondly, many patients who initially respond to trastuzumab ultimately develop disease progression. To overcome these problems, we employed virus-mediated HER2 transduction and photoimmunotherapy (PIT) which involves trastuzumab conjugated with a photosensitizer, trastuzumab-IR700, and irradiation of near-infrared light. We hypothesized that the gene transduction technique together with PIT would expand the range of tumor entities suitable for trastuzumab-based therapy and improve its antitumor activity. The HER2-extracellular domain (ECD) was transduced by the adenoviral vector, Ad-HER2-ECD, and PIT with trastuzumab-IR700 was applied in the HER2-negative cancer cells. Ad-HER2-ECD can efficiently transduce HER2-ECD into HER2-negative human cancer cells. PIT with trastuzumab-IR700 induced direct cell membrane destruction of Ad-HER2-ECD-transduced HER2-negative cancer cells. Novel combination of viral transduction of a target antigen and an antibody-based PIT would expand and potentiate molecular-targeted therapy even for target-negative or attenuated cancer cells.
C1 [Shimoyama, Kyoko; Kagawa, Shunsuke; Ishida, Michihiro; Watanabe, Shinichiro; Noma, Kazuhiro; Takehara, Kiyoto; Tazawa, Hiroshi; Hashimoto, Yuuri; Tanabe, Shunsuke; Fujiwara, Toshiyoshi] Okayama Univ, Grad Sch Med Dent & Pharmacol Sci, Dept Surg Gastroenterol, Kita Ku, Okayama 7008558, Japan.
[Tazawa, Hiroshi] Okayama Univ Hosp, Ctr Innovat Clin Med, Okayama, Japan.
[Matsuoka, Junji] Okayama Univ Hosp, Dept Palliat Care, Okayama, Japan.
[Kobayashi, Hisataka] NCI, Mol Imaging Program, Ctr Canc Res, US Natl Inst Hlth, Bethesda, MD 20892 USA.
RP Kagawa, S (reprint author), Okayama Univ, Grad Sch Med Dent & Pharmacol Sci, Dept Surg Gastroenterol, Kita Ku, 2-5-1 Shikata Cho, Okayama 7008558, Japan.
EM skagawa@md.okayama-u.ac.jp
RI TAZAWA, Hiroshi/B-2247-2011
OI TAZAWA, Hiroshi/0000-0003-4658-1050
FU Ministry of Education Culture, Sports, Science and Technology, Japan;
Ministry of Health, Labor and Welfare, Japan
FX We thank Tomoko Sueishi for her technical support. This study was
supported by grants-in-aid from the Ministry of Education Culture,
Sports, Science and Technology, Japan (Toshiyoshi Fujiwara, Hiroshi
Tazawa, Shunsuke Tanabe, and Shunsuke Kagawa) and grants from the
Ministry of Health, Labor and Welfare, Japan (Toshiyoshi Fujiwara).
NR 36
TC 4
Z9 4
U1 1
U2 11
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 FEB
PY 2015
VL 149
IS 3
BP 597
EP 605
DI 10.1007/s10549-015-3265-y
PG 9
WC Oncology
SC Oncology
GA CB6UC
UT WOS:000349761200004
PM 25616354
ER
PT J
AU Ryan, BM
Robles, AI
McClary, AC
Haznadar, M
Bowman, ED
Pine, SR
Brown, D
Khan, M
Shiraishi, K
Kohno, T
Okayama, H
Modali, R
Yokota, J
Harris, CC
AF Ryan, Brd M.
Robles, Ana I.
McClary, Andrew C.
Haznadar, Majda
Bowman, Elise D.
Pine, Sharon R.
Brown, Derek
Khan, Mohammed
Shiraishi, Kouya
Kohno, Takashi
Okayama, Hirokazu
Modali, Ramakrishna
Yokota, Jun
Harris, Curtis C.
TI Identification of a Functional SNP in the 3 ' UTR of CXCR2 That Is
Associated with Reduced Risk of Lung Cancer
SO CANCER RESEARCH
LA English
DT Article
ID MICRORNA BINDING-SITES; GENETIC-VARIATION; ALTERS SUSCEPTIBILITY;
UNTRANSLATED REGION; TARGET SITES; INTERLEUKIN-8; SENESCENCE;
POLYMORPHISMS; MECHANISM; PROMOTER
AB Global changes in gene expression accompany the development of cancer. Thus, inherited variants in miRNA-binding sites are likely candidates for conferring inherited susceptibility. Using an in silico approach, we compiled a comprehensive list of SNPs predicted to modulate miRNA binding in genes from several key lung cancer pathways. We then investigated whether these SNPs were associated with lung cancer risk in two independent populations. In general, SNPs in miRNA-binding sites are rare. However, some allelic variation was observed. We found that rs1126579 in CXCR2 was associated with a reduced risk of lung cancer in both European American [ORTT (vs). (CC) 0.56 (0.37-0.88); P = 0.008] and Japanese [ORTT (vs.) (CC)0.62 (0.38-1.00); P = 0.049] populations. Furthermore, we found that the SNP disrupted a novel binding site for miR-516a-3p, led to a moderate increase in CXCR2 mRNA and protein expression, and increased MAPK signaling. Moreover, analysis of rs1126579 with serum levels of IL8, its endogenous ligand, supported an interaction whereby rs1126579-T and high serum IL8 conferred synergistic protection from lung cancer. Our findings demonstrate a function for a 3 ' UTR SNP in modulating CXCR2 expression, signaling, and susceptibility to lung cancer. (C) 2014 AACR.
C1 [Ryan, Brd M.; Robles, Ana I.; McClary, Andrew C.; Haznadar, Majda; Bowman, Elise D.; Brown, Derek; Khan, Mohammed; Okayama, Hirokazu; Harris, Curtis C.] NCI, Human Carcinogenesis Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
[McClary, Andrew C.] Stanford Univ Hosp & Clin, Dept Pathol, Stanford, CA USA.
[Pine, Sharon R.] Rutgers State Univ, Rutgers Canc Inst New Jersey, New Brunswick, NJ 08903 USA.
[Shiraishi, Kouya; Kohno, Takashi; Okayama, Hirokazu; Yokota, Jun] Natl Canc Ctr, Res Inst, Div Genome Biol, Chuo Ku, Tokyo 104, Japan.
[Modali, Ramakrishna] BioServe Ltd, Beltsville, MD USA.
RP Harris, CC (reprint author), NCI, Human Carcinogenesis Lab, Bldg 37,Room 3068,37 Convent Dr,MSC 4258, Bethesda, MD 20892 USA.
EM Curtis_Harris@nih.gov
FU Intramural Program of the Centre for Cancer Research, NCI (Bethesda,
MD); Ministry of Health, Labor, and Welfare of Japan; National Cancer
Center Research and Development Fund [26-A-8]
FX This work was supported by the Intramural Program of the Centre for
Cancer Research, NCI (Bethesda, MD). This work was also supported in
part by Grants-in-Aid from the Ministry of Health, Labor, and Welfare of
Japan for the 3rd term Comprehensive 10-year Strategy for Cancer
Control, and by the National Cancer Center Research and Development Fund
(26-A-8).
NR 50
TC 13
Z9 14
U1 4
U2 14
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 FEB 1
PY 2015
VL 75
IS 3
BP 566
EP 575
DI 10.1158/0008-5472.CAN-14-2101
PG 10
WC Oncology
SC Oncology
GA CB7XE
UT WOS:000349841200010
PM 25480945
ER
PT J
AU Wohlfarth, A
Scheidweiler, KB
Castaneto, M
Gandhi, AS
Desrosiers, NA
Klette, KL
Martin, TM
Huestis, MA
AF Wohlfarth, Ariane
Scheidweiler, Karl B.
Castaneto, Marisol
Gandhi, Adarsh S.
Desrosiers, Nathalie A.
Klette, Kevin L.
Martin, Thomas M.
Huestis, Marilyn A.
TI Urinary prevalence, metabolite detection rates, temporal patterns and
evaluation of suitable LC-MS/MS targets to document synthetic
cannabinoid intake in US military urine specimens
SO CLINICAL CHEMISTRY AND LABORATORY MEDICINE
LA English
DT Article
DE liquid chromatography tandem mass spectrometry (LC-MS/MS); metabolites;
qualitative confirmation; synthetic cannabinoids; urine
ID RESOLUTION MASS-SPECTROMETRY; SIMULTANEOUS QUANTIFICATION; QUANTITATIVE
MEASUREMENT; SMOKING MIXTURES; ILLEGAL PRODUCTS; JWH-018;
IDENTIFICATION; DERIVATIVES; AM-2201; FUBINACA
AB Background: Identifying synthetic cannabinoid designer drug abuse challenges toxicologists and drug testing programs. The best analytical approach for reliably documenting intake of emerging synthetic cannabinoids is unknown. Primarily metabolites are found in urine, but optimal metabolite targets remain unknown, and definitive identification is complicated by converging metabolic pathways.
Methods: We screened 20,017 US military urine specimens collected from service members worldwide for synthetic cannabinoids between July 2011 and June 2012. We confirmed 1432 presumptive positive and 1069 presumptive negative specimens by qualitative liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis including 29 biomarkers for JWH-018, JWH-073, JWH-081, JWH-122, JWH-200, JWH-210, JWH-250, RCS-4, AM2201 and MAM2201. Specimen preparation included enzyme hydrolysis and acetonitrile precipitation prior to LC-MS/ MS analysis. We evaluated individual synthetic cannabinoid metabolite detection rates, prevalence, temporal patterns and suitable targets for analytical procedures.
Results: Prevalence was 1.4% with 290 confirmed positive specimens, 92% JWH-018, 54% AM2201 and 39% JWH-122 metabolites. JWH-073, JWH-210 and JWH-250 also were identified in 37%, 4% and 8% of specimens, respectively. The United States Army Criminal Investigation Command seizure pattern for synthetic cannabinoid compounds matched our urine specimen results over the time frame of the study. Apart from one exception (AM2201), no parent compounds were observed.
Conclusions: Hydroxyalkyl metabolites accounted for most confirmed positive tests, and in many cases, two metabolites were identified, increasing confidence in the results, and improving detection rates. These data also emphasize the need for new designer drug metabolism studies to provide relevant targets for synthetic cannabinoid identification.
C1 [Scheidweiler, Karl B.; Castaneto, Marisol; Gandhi, Adarsh S.; Desrosiers, Nathalie A.; Klette, Kevin L.; Huestis, Marilyn A.] NIDA, NIH, IRP, Baltimore, MD 21224 USA.
[Wohlfarth, Ariane; Scheidweiler, Karl B.; Castaneto, Marisol; Gandhi, Adarsh S.; Desrosiers, Nathalie A.] NIDA, Natl Inst Chem, Intramural Res Program, Baltimore, MD 21224 USA.
[Wohlfarth, Ariane; Scheidweiler, Karl B.; Castaneto, Marisol; Gandhi, Adarsh S.; Desrosiers, Nathalie A.] NIDA, Natl Inst Drug Metab, Intramural Res Program, Baltimore, MD 21224 USA.
[Castaneto, Marisol; Desrosiers, Nathalie A.] Univ Maryland, Toxicol Program, Baltimore, MD 21201 USA.
[Klette, Kevin L.; Martin, Thomas M.] Off Secretary Def Personnel & Readiness, Drug Testing & Program Policy, Washington, DC USA.
RP Huestis, MA (reprint author), NIDA, NIH, IRP, 251 Bayview Blvd Suite 200,Room 05A-721, Baltimore, MD 21224 USA.
EM mhuestis@intra.nida.nih.gov
FU Intramural Research Program of the National Institute on Drug Abuse
(NIDA-IRP); Department of Defense Counter Narcotics Program
[Y3-DA-1116-01]; NIDA-IRP [Y3-DA-1116-01]
FX This research was funded by the Intramural Research Program of the
National Institute on Drug Abuse (NIDA-IRP) and by an Interagency
Agreement (Y3-DA-1116-01) between Department of Defense Counter
Narcotics Program and NIDA-IRP.
NR 39
TC 8
Z9 9
U1 3
U2 20
PU WALTER DE GRUYTER GMBH
PI BERLIN
PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY
SN 1434-6621
EI 1437-4331
J9 CLIN CHEM LAB MED
JI Clin. Chem. Lab. Med.
PD FEB
PY 2015
VL 53
IS 3
BP 423
EP 434
DI 10.1515/cclm-2014-0612
PG 12
WC Medical Laboratory Technology
SC Medical Laboratory Technology
GA CB3VY
UT WOS:000349558500019
PM 25263309
ER
PT J
AU Drosten, C
Muth, D
Corman, VM
Hussain, R
Al Masri, M
HajOmar, W
Landt, O
Assiri, A
Eckerle, I
Al Shangiti, A
Al-Tawfig, JA
Albarrak, A
Zumla, A
Rambaut, A
Memish, ZA
AF Drosten, Christian
Muth, Doreen
Corman, Victor M.
Hussain, Raheela
Al Masri, Malaki
HajOmar, Waleed
Landt, Olfert
Assiri, Abdullah
Eckerle, Isabella
Al Shangiti, Ali
Al-Tawfig, Jaffar A.
Albarrak, Ali
Zumla, Alimuddin
Rambaut, Andrew
Memish, Ziad A.
TI An Observational, Laboratory-Based Study of Outbreaks of Middle East
Respiratory Syndrome Coronavirus in Jeddah and Riyadh, Kingdom of Saudi
Arabia, 2014
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Article
DE MERS-coronavirus; outbreak; nosocomial transmission; virus isolation;
transmission infection control
ID MERS-CORONAVIRUS; INFECTION; EPIDEMIOLOGY
AB Background. In spring 2014, a sudden rise in the number of notified Middle East respiratory syndrome coronavirus (MERS-CoV) infections occurred across Saudi Arabia with a focus in Jeddah. Hypotheses to explain the outbreak pattern include increased surveillance, increased zoonotic transmission, nosocomial transmission, and changes in viral transmissibility, as well as diagnostic laboratory artifacts.
Methods. Diagnostic results from Jeddah Regional Laboratory were analyzed. Viruses from the Jeddah outbreak and viruses occurring during the same time in Riyadh, Al-Kharj, and Madinah were fully or partially sequenced. A set of 4 single-nucleotide polymorphisms distinctive to the Jeddah outbreak were determined from additional viruses. Viruses from Riyadh and Jeddah were isolated and studied in cell culture.
Results. Up to 481 samples were received per day for reverse transcription polymerase chain reaction (RT-PCR) testing. A laboratory proficiency assessment suggested positive and negative results to be reliable. Forty-nine percent of 168 positive-testing samples during the Jeddah outbreak stemmed from King Fahd Hospital. All viruses from Jeddah were monophyletic and similar, whereas viruses from Riyadh were paraphyletic and diverse. A hospital-associated transmission cluster, to which cases in Indiana (United States) and the Netherlands belonged, was discovered in Riyadh. One Jeddah-type virus was found in Riyadh, with matching travel history to Jeddah. Virus isolates representing outbreaks in Jeddah and Riyadh were not different from MERS-CoV EMC/2012 in replication, escape of interferon response, or serum neutralization.
Conclusions. Virus shedding and virus functions did not change significantly during the outbreak in Jeddah. These results suggest the outbreaks to have been caused by biologically unchanged viruses in connection with nosocomial transmission.
C1 [Drosten, Christian; Muth, Doreen; Corman, Victor M.; Eckerle, Isabella] Univ Bonn, Med Ctr, Inst Virol, Hannover, Germany.
[Drosten, Christian; Corman, Victor M.] German Ctr Infect Res, Hannover, Germany.
[Hussain, Raheela] Minist Hlth, Jeddah Reg Lab, Riyadh, Saudi Arabia.
[Al Masri, Malaki; Assiri, Abdullah; Zumla, Alimuddin; Memish, Ziad A.] Minist Hlth, Global Ctr Mass Gatherings Med, Riyadh, Saudi Arabia.
[HajOmar, Waleed; Al Shangiti, Ali] Minist Hlth, Reg Lab, Riyadh, Saudi Arabia.
[Landt, Olfert] Tib Molbiol, Berlin, Germany.
[Al-Tawfig, Jaffar A.] Johns Hopkins Aramco Healthcare, Dhahran, Saudi Arabia.
[Al-Tawfig, Jaffar A.] Indiana Univ Sch Med, Indianapolis, IN 46202 USA.
[Albarrak, Ali] Prince Sultan Mil Med City, Riyadh, Saudi Arabia.
[Zumla, Alimuddin] UCL, Div Infect & Immun, London WC1E 6BT, England.
[Zumla, Alimuddin] Univ Coll London Hosp Natl Hlth Serv Fdn Trust, Natl Inst Hlth Res Biomed Res Ctr, London, England.
[Rambaut, Andrew] Univ Edinburgh, Inst Evolutionary Biol, Ctr Infect Immun & Evolut, Edinburgh EH8 9YL, Midlothian, Scotland.
[Rambaut, Andrew] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Memish, Ziad A.] Al Faisal Univ, Riyadh, Saudi Arabia.
RP Memish, ZA (reprint author), Al Faisal Univ, Altakhasusi Rd, Riyadh, Saudi Arabia.
EM zmemish@yahoo.com
OI Rambaut, Andrew/0000-0003-4337-3707; Zumla,
Alimuddin/0000-0002-5111-5735; Corman, Victor Max/0000-0002-3605-0136
FU European Commission [223498]; ANTIGONE [278976]; German Research Council
[01KIO701, DR 772/3-1]; European Commission; Ministry of Research
(Germany); University College London Hospitals National Health Service
Foundation Trust; National Institute of Health Research, Biomedical
Research Centre, University College London Hospitals; European &
Developing Countries Clinical Trials Partnership; European Commission
Project RiD-RTI; European Commission under the project PREDEMICS
[278433]
FX C. D. acknowledges support from the European Commission
(www.emperie.eu/emp/; contract number 223498) and ANTIGONE (contract
number 278976), infrastructural support from the German Centre for
Infection Research, the German Ministry for Research and Education, and
the German Research Council (grant number 01KIO701 and DR 772/3-1). I.
E., D. M., and V. M. C. acknowledge grant support from the European
Commission, Ministry of Research (Germany), and German Research Council.
A. Z. acknowledges support from the University College London Hospitals
National Health Service Foundation Trust, the National Institute of
Health Research, Biomedical Research Centre, University College London
Hospitals, the European & Developing Countries Clinical Trials
Partnership, and the European Commission Project RiD-RTI. A. R.
acknowledges support by the European Commission under the project
PREDEMICS (contract number 278433).
NR 19
TC 53
Z9 54
U1 2
U2 23
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 FEB 1
PY 2015
VL 60
IS 3
BP 369
EP 377
DI 10.1093/cid/ciu812
PG 9
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA CB6UG
UT WOS:000349761600015
PM 25323704
ER
PT J
AU Sun, KX
Gao, Z
Gui, P
Wang, R
Oguzman, I
Xu, XC
Vasanth, K
Zhou, QF
Shung, KK
AF Sun, Kexu
Gao, Zheng
Gui, Ping
Wang, Rui
Oguzman, Ismail
Xu, Xiaochen
Vasanth, Karthik
Zhou, Qifa
Shung, K. Kirk
TI A 180-V-pp Integrated Linear Amplifier for Ultrasonic Imaging
Applications in a High-Voltage CMOS SOI Technology
SO IEEE TRANSACTIONS ON CIRCUITS AND SYSTEMS II-EXPRESS BRIEFS
LA English
DT Article
DE High voltage (HV); linear amplifier; second-order harmonic distortion
(HD2); tissue harmonic imaging (THI); total harmonic distortion (THD);
ultrasonic imaging; voltage swing
AB This brief presents a monolithically integrated fully differential linear HV amplifier as the driver of an ultrasonic transducer. The linear amplifier is capable of transmitting HV arbitrary signals with a very low harmonic distortion, which is suitable for tissue harmonic imaging and other ultrasonic modes for enhanced imaging quality. The amplifier is designed and implemented using the 0.7-mu m CMOS silicon-on-insulator process with 120-V devices. The amplifier, when driving a load of 300 pF in parallel with 100 Omega, is capable of transmitting a sine-wave signal with a frequency of up to 4.4 MHz, a maximum signal swing of 180 V-pp, and a second-order harmonic distortion (HD2) of -56 dBc but only dissipating an average power of 62 mW with a 0.1% duty cycle.
C1 [Sun, Kexu; Gui, Ping; Wang, Rui] So Methodist Univ, Lyle Sch Engn, Dept Elect Engn, Dallas, TX 75205 USA.
[Gao, Zheng] So Methodist Univ, Dallas, TX 75205 USA.
[Oguzman, Ismail; Xu, Xiaochen; Vasanth, Karthik] Texas Instruments Inc, Dallas, TX 75243 USA.
[Zhou, Qifa; Shung, K. Kirk] Univ So Calif, NIH, Ultrasound Transducer Resource Ctr, Los Angeles, CA 90089 USA.
RP Sun, KX (reprint author), So Methodist Univ, Lyle Sch Engn, Dept Elect Engn, Dallas, TX 75205 USA.
EM pgui@smu.edu
FU Texas Instruments Incorporated; Semiconductor Research Corporation/Texas
Analog Center of Excellence (TxACE) [1836.043]
FX This work was supported in part by Texas Instruments Incorporated and in
part by the Semiconductor Research Corporation/Texas Analog Center of
Excellence (TxACE) under Project 1836.043. This brief was recommended by
Associate Editor R. Rieger.
NR 15
TC 1
Z9 1
U1 0
U2 6
PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC
PI PISCATAWAY
PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA
SN 1549-7747
EI 1558-3791
J9 IEEE T CIRCUITS-II
JI IEEE Trans. Circuits Syst. II-Express Briefs
PD FEB
PY 2015
VL 62
IS 2
SI SI
BP 149
EP 153
DI 10.1109/TCSII.2014.2387687
PG 5
WC Engineering, Electrical & Electronic
SC Engineering
GA CB5NR
UT WOS:000349675000011
PM 25914609
ER
PT J
AU Nath, A
AF Nath, Avindra
TI Neuroinfectious Diseases A Crisis in Neurology and a Call for Action
SO JAMA NEUROLOGY
LA English
DT Editorial Material
ID ENCEPHALITIS; PREDICTORS
C1 NINDS, Sect Infect Nervous Syst, NIH, Bethesda, MD 20892 USA.
RP Nath, A (reprint author), NINDS, Sect Infect Nervous Syst, NIH, Room 7C-103,Bldg 10,10 Ctr Dr, Bethesda, MD 20892 USA.
EM natha@ninds.nih.gov
FU Intramural NIH HHS [, ZIA NS003130-06]
NR 10
TC 2
Z9 2
U1 0
U2 3
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 2168-6149
EI 2168-6157
J9 JAMA NEUROL
JI JAMA Neurol.
PD FEB
PY 2015
VL 72
IS 2
BP 143
EP 144
DI 10.1001/jamaneurol.2014.3442
PG 2
WC Clinical Neurology
SC Neurosciences & Neurology
GA CB4SU
UT WOS:000349619200002
PM 25485794
ER
PT J
AU Nash, RA
Hutton, GJ
Racke, MK
Popat, U
Devine, SM
Griffith, LM
Muraro, PA
Openshaw, H
Sayre, PH
Stuve, O
Arnold, DL
Spychala, ME
McConville, KC
Harris, KM
Phippard, D
Georges, GE
Wundes, A
Kraft, GH
Bowen, JD
AF Nash, Richard A.
Hutton, George J.
Racke, Michael K.
Popat, Uday
Devine, Steven M.
Griffith, Linda M.
Muraro, Paolo A.
Openshaw, Harry
Sayre, Peter H.
Stueve, Olaf
Arnold, Douglas L.
Spychala, Meagan E.
McConville, Kaitlyn C.
Harris, Kristina M.
Phippard, Deborah
Georges, George E.
Wundes, Annette
Kraft, George H.
Bowen, James D.
TI High-Dose Immunosuppressive Therapy and Autologous Hematopoietic Cell
Transplantation for Relapsing-Remitting Multiple Sclerosis (HALT-MS) A
3-Year Interim Report
SO JAMA NEUROLOGY
LA English
DT Article
ID DISEASE-ACTIVITY; OUTCOME MEASURE; WORKING PARTY; BLOOD; TRIAL;
NATALIZUMAB; REPERTOIRE; GUIDELINES; EXPERIENCE
AB IMPORTANCE Most patients with relapsing-remitting (RR) multiple sclerosis (MS) who receive approved disease-modifying therapies experience breakthrough disease and accumulate neurologic disability. High-dose immunosuppressive therapy (HDIT) with autologous hematopoietic cell transplant (HCT) may, in contrast, induce sustained remissions in early MS.
OBJECTIVE To evaluate the safety, efficacy, and durability of MS disease stabilization through 3 years after HDIT/HCT.
DESIGN, SETTING, AND PARTICIPANTS Hematopoietic Cell Transplantation for Relapsing-Remitting Multiple Sclerosis (HALT-MS) is an ongoing, multicenter, single-arm, phase 2 clinical trial of HDIT/HCT for patients with RRMS who experienced relapses with loss of neurologic function while receiving disease-modifying therapies during the 18 months before enrolling. Participants are evaluated through 5 years after HCT. This report is a prespecified, 3-year interim analysis of the trial. Thirty-six patients with RRMS from referral centers were screened; 25 were enrolled.
INTERVENTIONS Autologous peripheral blood stem cell grafts were CD34(+) selected; the participants then received high-dose treatment with carmustine, etoposide, cytarabine, and melphalan as well as rabbit antithymocyte globulin before autologous HCT.
MAIN OUTCOMES AND MEASURES The primary end point of HALT-MS is event-free survival defined as survival without death or disease activity from any one of the following outcomes: (1) confirmed loss of neurologic function, (2) clinical relapse, or (3) new lesions observed on magnetic resonance imaging. Toxic effects are reported using National Cancer Institute Common Terminology Criteria for Adverse Events.
RESULTS Grafts were collected from 25 patients, and 24 of these individuals received HDIT/HCT. The median follow-up period was 186 weeks (interquartile range, 176-250) weeks). Overall event-free survival was 78.4%(90% CI, 60.1%-89.0%) at 3 years. Progression-free survival and clinical relapse-free survival were 90.9%(90% CI, 73.7%-97.1%) and 86.3%(90% CI, 68.1%-94.5%), respectively, at 3 years. Adverse events were consistent with expected toxic effects associated with HDIT/HCT, and no acute treatment-related neurologic adverse events were observed. Improvements were noted in neurologic disability, quality-of-life, and functional scores.
CONCLUSIONS AND RELEVANCE At 3 years, HDIT/HCT without maintenance therapy was effective for inducing sustained remission of active RRMS and was associated with improvements in neurologic function. Treatment was associated with few serious early complications or unexpected adverse events.
C1 [Nash, Richard A.] Colorado Blood Canc Inst, Denver, CO 80218 USA.
[Hutton, George J.] Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA.
[Racke, Michael K.] Ohio State Univ, Dept Neurol & Neurosci, Columbus, OH 43210 USA.
[Popat, Uday] Univ Texas MD Anderson Canc Ctr, Dept Stem Cell Transplantat, Div Canc Med, Houston, TX 77030 USA.
[Devine, Steven M.] Ohio State Univ, Med Ctr, Dept Internal Med, Blood & Marrow Transplant Program,Div Hematol, Columbus, OH 43210 USA.
[Griffith, Linda M.] NIAID, Div Allergy Immunol & Transplantat, NIH, Bethesda, MD 20892 USA.
[Muraro, Paolo A.] Univ London Imperial Coll Sci Technol & Med, Dept Med, Div Brain Sci, London, England.
[Openshaw, Harry] City Hope Natl Med Ctr, Dept Neurol, Duarte, CA 91010 USA.
[Sayre, Peter H.] Univ Calif San Francisco, Med Ctr, San Francisco, CA USA.
[Sayre, Peter H.] Immune Tolerance Network, Clin Trials Grp, San Francisco, CA USA.
[Stueve, Olaf] Univ Texas SW Med Ctr Dallas, Dept Neurol & Neurotherapeut, Dallas, TX 75390 USA.
[Stueve, Olaf] Vet Affairs North Texas Hlth Care Syst, Neurol Sect, Dallas, TX USA.
[Arnold, Douglas L.] McGill Univ, Montreal Neurol Inst & Hosp, Montreal, PQ, Canada.
[Arnold, Douglas L.] NeuroRx, Montreal, PQ, Canada.
[Spychala, Meagan E.; McConville, Kaitlyn C.] Rho Inc, Chapel Hill, NC USA.
[Harris, Kristina M.; Phippard, Deborah] Immune Tolerance Network, San Francisco, CA USA.
[Georges, George E.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA.
[Georges, George E.] Univ Washington, Med Ctr, Div Med Oncol, Seattle, WA 98195 USA.
[Wundes, Annette] Univ Washington, Med Ctr, Dept Neurol, Seattle, WA 98195 USA.
[Kraft, George H.] Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA.
[Bowen, James D.] Swedish Neurosci Inst, Seattle, WA USA.
RP Nash, RA (reprint author), Colorado Blood Canc Inst, 1721 E 19th Ave,Stes 200 & 300, Denver, CO 80218 USA.
EM richard.nash@healthonecares.com
FU Division of Allergy, Immunology and Transplantation, National Institute
of Allergy and Infectious Diseases (DAIT-NIAID), NIH; ITN [N01
AI015416]; DAIT-NIAID [HHSN272200800029C, HHSN272200900057C]
FX This work was sponsored by the Division of Allergy, Immunology and
Transplantation, National Institute of Allergy and Infectious Diseases
(DAIT-NIAID), NIH, and was conducted by the ITN (grant N01 AI015416),
and the DAIT-NIAID funded statistical and clinical coordinating centers
(contracts HHSN272200800029C and HHSN272200900057C). Baxter Healthcare
Corporation supplied the Isolex 300i Magnetic Cell Selection System
machines, Disposable Sets, and CD34 Reagent Kits used for the HALT-MS
clinical trial to DAIT, NIAID, without charge.
NR 34
TC 35
Z9 35
U1 5
U2 21
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 2168-6149
EI 2168-6157
J9 JAMA NEUROL
JI JAMA Neurol.
PD FEB
PY 2015
VL 72
IS 2
BP 159
EP 169
DI 10.1001/jamaneurol.2014.3780
PG 11
WC Clinical Neurology
SC Neurosciences & Neurology
GA CB4SU
UT WOS:000349619200007
PM 25546364
ER
PT J
AU Schleider, JL
Ginsburg, GS
Keeton, CP
Weisz, JR
Birmaher, B
Kendall, PC
Piacentini, J
Sherrill, J
Walkup, JT
AF Schleider, Jessica L.
Ginsburg, Golda S.
Keeton, Courtney P.
Weisz, John R.
Birmaher, Boris
Kendall, Phillip C.
Piacentini, John
Sherrill, Joel
Walkup, John T.
TI Parental Psychopathology and Treatment Outcome for Anxious Youth: Roles
of Family Functioning and Caregiver Strain
SO JOURNAL OF CONSULTING AND CLINICAL PSYCHOLOGY
LA English
DT Article
DE mediation; parental psychopathology; youth anxiety treatment; family
functioning
ID CHILDHOOD ANXIETY DISORDERS; ADOLESCENT PSYCHIATRIC-DISORDERS; MULTIPLE
MEDIATOR MODELS; TREATMENT RESPONSE; FOLLOW-UP; CHILDREN; BURDEN; SCALE;
PREDICTORS; CAMS
AB Objective: Research has examined the effects of parental psychopathology, family functioning, and caregiver strain on treatment response in anxious youths. Although these variables have shown individual links to youth treatment response, theoretical models for their combined effects remain unexplored. This study tested the hypothesis that improvements in family functioning and reductions in caregiver strain explained the effects of parental psychopathology on youth treatment outcome in an anxiety treatment trial. Method: A multiple mediation technique was used to test the proposed model across independent evaluator (IE), parent, and youth informants in 488 youths, aged 7-17 years (50% female; mean age = 10.7) meeting Diagnostic and Statistical Manual of Mental Disorders criteria for social phobia, separation anxiety, and/or generalized anxiety disorder. Youths were randomized to receive 12 weeks of cognitive-behavioral treatment (Coping Cat), medication (sertraline), their combination, or a pill placebo. At pre- and posttreatment, parents completed self-report measures of global psychopathology symptoms, family functioning, and caregiver strain; parents, youths, and IEs rated youths' anxiety symptom severity. Results: Changes in family functioning and caregiver strain jointly explained relations between parental psychopathology and reductions in youth anxiety. Specifically, across IE and parent informants, families with higher pretreatment parental psychopathology showed more improvement in family functioning and caregiver strain, which in turn predicted greater youth anxiety reductions. Further, higher pretreatment parental psychopathology predicted greater caregiver strain reductions and, in turn, greater youth anxiety reductions, based on youths' reports of their own anxiety. Conclusions: Findings suggest that improvements in family functioning and reductions in caregiver strain can influence treatment outcomes for anxious youths, especially among youths with more distressed parents.
C1 [Schleider, Jessica L.; Weisz, John R.] Harvard Univ, Cambridge, MA 02138 USA.
[Ginsburg, Golda S.; Keeton, Courtney P.] Johns Hopkins Univ, Sch Med, Baltimore, MD 21218 USA.
[Birmaher, Boris] Univ Pittsburgh, Pittsburgh, PA 15260 USA.
[Birmaher, Boris] Univ Pittsburgh, Med Ctr, Pittsburgh, PA 15260 USA.
[Kendall, Phillip C.] Temple Univ, Philadelphia, PA 19122 USA.
[Piacentini, John] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Los Angeles, CA 90024 USA.
[Sherrill, Joel] NIMH, Bethesda, MD 20892 USA.
[Walkup, John T.] Weill Cornell Med Coll, New York, NY USA.
[Walkup, John T.] New York Presbyterian Hosp, New York, NY USA.
RP Schleider, JL (reprint author), Harvard Univ, Dept Psychol, 33 Kirkland St, Cambridge, MA 02138 USA.
EM jschleider@fas.harvard.edu
FU National Institute of Mental Health (NIMH) [MH64089, MH64107, MH64003,
MH63747, MH064092, MH64088]; Pfizer Pharmaceuticals
FX This study was supported by National Institute of Mental Health (NIMH)
Grants MH64089, MH64107, MH64003, MH63747, MH064092, and MH64088. Views
expressed within this article represent those of the authors and are not
intended to represent the position of NIMH, the National Institutes of
Health, or the Department of Health and Human Services. Boris Birmaher
receives book royalties from Random House, Inc., UpToDate, and
Lippincott Williams & Wilkins. Phillip C. Kendall receives royalties for
the sale of books and anxiety treatment materials. John Piacentini
receives research support from Pfizer Pharmaceuticals.
NR 74
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Z9 6
U1 6
U2 31
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 FEB
PY 2015
VL 83
IS 1
BP 213
EP 224
DI 10.1037/a0037935
PG 12
WC Psychology, Clinical
SC Psychology
GA CB4PY
UT WOS:000349611500019
PM 25222799
ER
PT J
AU Zablotsky, B
Pringle, BA
Colpe, LJ
Kogan, MD
Rice, C
Blumberg, SJ
AF Zablotsky, Benjamin
Pringle, Beverly A.
Colpe, Lisa J.
Kogan, Michael D.
Rice, Catherine
Blumberg, Stephen J.
TI Service and Treatment Use Among Children Diagnosed With Autism Spectrum
Disorders
SO JOURNAL OF DEVELOPMENTAL AND BEHAVIORAL PEDIATRICS
LA English
DT Article
DE autism spectrum disorder; intellectual disability; national surveys
ID PSYCHOTROPIC MEDICATION USE; INTELLECTUAL DISABILITY; CARE NEEDS;
HEALTH; EXPENDITURES; PREVALENCE; ACCESS; EXPERIENCES; FAMILIES; SAMPLE
AB Objective: Children diagnosed with autism spectrum disorder (ASD) require substantial support to address not only core ASD symptoms but also a range of co-occurring conditions. This study explores treatment and service use among children with ASD with and without intellectual disability (ID) and parents' perception of unmet needs from these treatments. Methods: Data were retrieved from a probability-based national sample of 2077 children diagnosed with ASD, ID, or both (ASD and ID). Weighted multivariate logistic regressions examined differences between diagnostic groups for current medication and service utilization with a subanalysis exploring differences among those with co-occurring psychiatric conditions. Additional modeling examined parents' perception of unmet needs. Results: Children diagnosed with ASD and ID were significantly more likely to be receiving current medication and services when compared with children with ID only or ASD only. Children with a co-occurring psychiatric diagnosis, from all 3 diagnostic groups, were more likely to be receiving a current medication, but not more likely to be receiving a current service when compared with children without a co-occurring psychiatric diagnosis. Children with ASD and a co-occurring psychiatric diagnosis were significantly more likely to have parents who reported unmet needs when compared with parents of children with ASD without a co-occurring psychiatric diagnosis. Conclusions: Children diagnosed with ASD and ID, especially those with a comorbid psychiatric condition, represent a vulnerable population with substantial rates of current service (98%) and medication (67%) usage, but despite these high rates, approximately 30% of parents report that their child's developmental needs are still not being met by their current treatment and services.
C1 [Zablotsky, Benjamin; Blumberg, Stephen J.] Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Hyattsville, MD 20782 USA.
[Pringle, Beverly A.] NIMH, Off Res Dispar & Global Mental Hlth, Bethesda, MD 20892 USA.
[Colpe, Lisa J.] NIMH, Div Serv & Intervent Res, Bethesda, MD 20892 USA.
[Kogan, Michael D.] Maternal & Child Hlth Bur, Off Epidemiol & Res, Rockville, MD USA.
[Rice, Catherine] Ctr Dis Control & Prevent, Natl Ctr Birth Defects & Dev Disabil, Atlanta, GA USA.
RP Zablotsky, B (reprint author), Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, 3311 Toledo Rd,Room 2118, Hyattsville, MD 20782 USA.
EM bzablotsky@cdc.gov
RI Rice, Catherine/D-6305-2016
FU Intramural CDC HHS [CC999999]
NR 38
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U1 1
U2 20
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0196-206X
EI 1536-7312
J9 J DEV BEHAV PEDIATR
JI J. Dev. Behav. Pediatr.
PD FEB-MAR
PY 2015
VL 36
IS 2
BP 98
EP 105
PG 8
WC Behavioral Sciences; Psychology, Developmental; Pediatrics
SC Behavioral Sciences; Psychology; Pediatrics
GA CB2HO
UT WOS:000349448000074
PM 25650952
ER
PT J
AU Barrett, AJ
AF Barrett, Austin John
TI Editorial: A new checkpoint in the path to GVHD? How bedside-to-bench
stem cell transplant studies can inform human GVHD biology
SO JOURNAL OF LEUKOCYTE BIOLOGY
LA English
DT Editorial Material
ID VERSUS-HOST-DISEASE; RISK
C1 [Barrett, Austin John] NHLBI, Stem Cell Allotransplantat Sect, Hematol Branch, US Natl Inst Hlth, Bethesda, MD 20892 USA.
RP Barrett, AJ (reprint author), US NIH, Stem Cell Allotransplantat Sect, Hematol Branch, CRC, 3-5330,10 Ctr Dr, Bethesda, MD 20892 USA.
EM barrettj@nhlbi.nih.gov
FU Intramural NIH HHS
NR 3
TC 0
Z9 0
U1 0
U2 1
PU FEDERATION AMER SOC EXP BIOL
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0741-5400
EI 1938-3673
J9 J LEUKOCYTE BIOL
JI J. Leukoc. Biol.
PD FEB
PY 2015
VL 97
IS 2
BP 213
EP 216
DI 10.1189/jlb.5CE0814-385
PG 4
WC Cell Biology; Hematology; Immunology
SC Cell Biology; Hematology; Immunology
GA CB2GB
UT WOS:000349443900002
PM 25649789
ER
PT J
AU Tarasenko, TN
Gomez-Rodriguez, J
McGuire, PJ
AF Tarasenko, Tatyana N.
Gomez-Rodriguez, Julio
McGuire, Peter J.
TI Impaired T cell function in argininosuccinate synthetase deficiency
SO JOURNAL OF LEUKOCYTE BIOLOGY
LA English
DT Article
DE immunity; arginine; metabolism; differentiation
ID L-ARGININE; ADAPTIVE IMMUNITY; GENE-EXPRESSION; ZETA-CHAIN; AMINO-ACID;
LYMPHOCYTES; METABOLISM; PROLIFERATION; CITRULLINE; LEUKEMIA
AB ASS1 is a cytosolic enzyme that plays a role in the conversion of citrulline to arginine. In human and mouse tissues, ASS1 protein is found in several components of the immune system, including the thymus and T cells. However, the role of ASS1 in these tissues remains to be defined. Considerable attention has been focused recently on the role of metabolism in T cell differentiation and function. Based on the expression of ASS1 in the immune system, we hypothesized that ASS1 deficiency would result in T cell defects. To evaluate this question, we characterized immune function in hypomorphic fold/fold mice. Analysis of splenic T cells by flow cytometry showed a marked reduction in T cell numbers with normal expression of activation surface markers. Gene therapy correction of liver ASS1 to enhance survival resulted in a partial recovery of splenic T cells for characterization. In vitro and in vivo studies demonstrated the persistence of the ASS1 enzyme defect in T cells and abnormal T cell differentiation and function. Overall, our work suggests that ASS1 plays a role in T cell function, and deficiency produces primary immune dysfunction. In addition, these data suggest that patients with ASS1 deficiency (citrullinemia type I) may have T cell dysfunction.
C1 [Tarasenko, Tatyana N.; Gomez-Rodriguez, Julio; McGuire, Peter J.] NHGRI, NIH, Bethesda, MD 20892 USA.
RP McGuire, PJ (reprint author), NHGRI, NIH, 49 Convent Dr,4A62, Bethesda, MD 20892 USA.
EM Peter.mcguire@nih.gov
FU U.S. National Institutes of Health, National Human Genome Research
Institute (NHGRI); Physician Scientist Development Program at the NHGRI
FX The intramural research program of the U.S. National Institutes of
Health, National Human Genome Research Institute (NHGRI) supported all
of the work herein. The authors thank Dr. Les Biesecker for his support
and the support of the Physician Scientist Development Program at the
NHGRI. The authors also thank Dr. Pamela Schwartzberg for her editorial
insights during preparation of this manuscript.
NR 32
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U1 0
U2 3
PU FEDERATION AMER SOC EXP BIOL
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0741-5400
EI 1938-3673
J9 J LEUKOCYTE BIOL
JI J. Leukoc. Biol.
PD FEB
PY 2015
VL 97
IS 2
BP 273
EP 278
DI 10.1189/jlb.1AB0714-365R
PG 6
WC Cell Biology; Hematology; Immunology
SC Cell Biology; Hematology; Immunology
GA CB2GB
UT WOS:000349443900008
PM 25492936
ER
PT J
AU Basu, S
Hubbard, B
Shevach, EM
AF Basu, Samik
Hubbard, Britany
Shevach, Ethan M.
TI Foxp3-mediated inhibition of Akt inhibits Glut1 (glucose transporter 1)
expression in human T regulatory cells
SO JOURNAL OF LEUKOCYTE BIOLOGY
LA English
DT Article
DE signal transduction; metabolism; lymphocyte; autoimmunity
ID FOXP3 TARGET GENES; CUTTING EDGE; ACTIVATION; METABOLISM; PATHWAYS
AB CD4(+)CD25(+)Foxp3(+)T(regs) have a diminished capacity to activate the PI3K/Akt pathway. Although blunted Akt activity is necessary to maintain T-reg function, the consequences of this altered signaling are unclear. Glut1 is a cell-surface receptor responsible for facilitating glucose transport across plasma membranes, whose expression is tightly coupled to costimulatory signals and Akt phosphorylation. Freshly isolated human T-regs were unable to up-regulate Glut1 in response to TCR and costimulatory signals compared with T-conv. Consequently, the ability of T-regs to use glucose was also reduced. Introduction of Foxp3 into T-conv inhibited Akt activation and Glut1 expression, indicating that Foxp3 can regulate Glut1. Finally, pharmacologic activation of Akt in T-regs can induce Glut1, overcoming the effects of Foxp3. Together, these results illustrate the molecular basis behind differential glucose metabolism in T-regs.
C1 [Basu, Samik; Hubbard, Britany; Shevach, Ethan M.] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA.
RP Shevach, EM (reprint author), NIAID, Immunol Lab, NIH, Bldg 10,Room 11N315,10 Ctr Dr, Bethesda, MD 20892 USA.
EM eshevach@niaid.nih.gov
FU Intramural Program of National Institute of Allergy and Infectious
Diseases (NIAID), U.S. National Institutes of Health; Cooperative
Research and Development Agreement (CRADA); Boerhinger-Ingelheim
FX This research was supported by the Intramural Program of National
Institute of Allergy and Infectious Diseases (NIAID), U.S. National
Institutes of Health, and by a Cooperative Research and Development
Agreement (CRADA) with Boerhinger-Ingelheim. The authors thank the NIAID
Flow Cytometry Section, particularly Elina Stregvensky and Bishop Hague
for all of their help in sorting our cells. The authors also thank the
Department of Transfusion Medicine for providing the blood donors.
NR 23
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U1 0
U2 3
PU FEDERATION AMER SOC EXP BIOL
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0741-5400
EI 1938-3673
J9 J LEUKOCYTE BIOL
JI J. Leukoc. Biol.
PD FEB
PY 2015
VL 97
IS 2
BP 279
EP 283
DI 10.1189/jlb.2AB0514-273RR
PG 5
WC Cell Biology; Hematology; Immunology
SC Cell Biology; Hematology; Immunology
GA CB2GB
UT WOS:000349443900009
PM 25492937
ER
PT J
AU Bigert, C
Gustavsson, P
Straif, K
Pesch, B
Bruning, T
Kendzia, B
Schuz, J
Stucker, I
Guida, F
Bruske, I
Wichmann, HE
Pesatori, AC
Landi, MT
Caporaso, N
Tse, LA
Yu, ITS
Siemiatycki, J
Pintos, J
Merletti, F
Mirabelli, D
Simonato, L
Jockel, KH
Ahrens, W
Pohlabeln, H
Tardon, A
Zaridze, D
Field, J
't Mannetje, A
Pearce, N
McLaughlin, J
Demers, P
Szeszenia-Dabrowska, N
Lissowska, J
Rudnai, P
Fabianova, E
Dumitru, RS
Bencko, V
Foretova, L
Janout, V
Boffetta, P
Forastiere, F
Bueno-de-Mesquita, B
Peters, S
Vermeulen, R
Kromhout, H
Olsson, AC
AF Bigert, Carolina
Gustavsson, Per
Straif, Kurt
Pesch, Beate
Bruening, Thomas
Kendzia, Benjamin
Schuez, Joachim
Stuecker, Isabelle
Guida, Florence
Brueske, Irene
Wichmann, Heinz-Erich
Pesatori, Angela C.
Landi, Maria Teresa
Caporaso, Neil
Tse, Lap Ah
Yu, Ignatius Tak-sun
Siemiatycki, Jack
Pintos, Javier
Merletti, Franco
Mirabelli, Dario
Simonato, Lorenzo
Joeckel, Karl-Heinz
Ahrens, Wolfgang
Pohlabeln, Hermann
Tardon, Adonina
Zaridze, David
Field, John
't Mannetje, Andrea
Pearce, Neil
McLaughlin, John
Demers, Paul
Szeszenia-Dabrowska, Neonila
Lissowska, Jolanta
Rudnai, Peter
Fabianova, Eleonora
Dumitru, Rodica Stanescu
Bencko, Vladimir
Foretova, Lenka
Janout, Vladimir
Boffetta, Paolo
Forastiere, Francesco
Bueno-de-Mesquita, Bas
Peters, Susan
Vermeulen, Roel
Kromhout, Hans
Olsson, Ann C.
TI Lung Cancer Risk Among Cooks When Accounting for Tobacco Smoking A
Pooled Analysis of Case-Control Studies From Europe, Canada, New
Zealand, and China
SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE
LA English
DT Article
ID AROMATIC-HYDROCARBONS PAHS; DNA-REPAIR GENES; MUTAGENIC ALDEHYDES;
PARTICULATE MATTER; OCCUPATIONAL-EXPOSURE; NONSMOKING WOMEN;
CASE-REFERENT; POPULATION; MEN; MORTALITY
AB Objectives: To investigate the risk of lung cancer among cooks, while controlling for smoking habits. Methods: We used data from the SYNERGY project including pooled information on lifetime work histories and smoking habits from 16 case-control studies conducted in Europe, Canada, New Zealand, and China. Results: Before adjustment for smoking, we observed an increased risk of lung cancer in male cooks, but not in female cooks. After adjusting, there was no increased risk and no significant exposure-response relationship. Nevertheless, subgroup analyses highlighted some possible excess risks of squamous cell carcinoma and small cell carcinoma in female cooks. Conclusions: There is evidence that lung cancer risks among cooks may be confounded by smoking. After adjustment, cooks did not experience an increased risk of lung cancer overall. The subgroup analyses showing some excess risks among female cooks require cautious interpretation.
C1 [Bigert, Carolina; Gustavsson, Per] Karolinska Inst, Inst Environm Med, SE-11365 Stockholm, Sweden.
[Straif, Kurt; Schuez, Joachim; Olsson, Ann C.] Int Agcy Res Canc, F-69372 Lyon, France.
[Pesch, Beate; Bruening, Thomas; Kendzia, Benjamin] Ruhr Univ Bochum IPA, German Social Accid Insurance Inst, Inst Prevent & Occupat Med, Bochum, Germany.
[Stuecker, Isabelle; Guida, Florence] Ctr Res Epidemiol & Populat Hlth CESP, INSERM, U1018, Environm Epidemiol Canc Team, F-94807 Villejuif, France.
[Stuecker, Isabelle; Guida, Florence] Univ Paris 11, UMRS 1018, F-94807 Villejuif, France.
[Brueske, Irene; Wichmann, Heinz-Erich] Deutsch Forschungszentrum Gesundheit & Umwelt, Inst Epidemiol 1, Neuherberg, Germany.
[Pesatori, Angela C.] Univ Milan, Dept Clin Sci & Community Hlth, Milan, Italy.
[Landi, Maria Teresa; Caporaso, Neil] NCI, Bethesda, MD 20892 USA.
[Tse, Lap Ah; Yu, Ignatius Tak-sun] Chinese Univ Hong Kong, Div Occupat & Environm Hlth, Sch Publ Hlth & Primary Care, Hong Kong, Hong Kong, Peoples R China.
[Siemiatycki, Jack; Pintos, Javier] Univ Montreal, Res Ctr, Univ Montreal Hosp Ctr, Montreal, PQ H3C 3J7, Canada.
[Merletti, Franco; Mirabelli, Dario] Univ Turin, Dept Med Sci, Canc Epidemiol Unit, I-10124 Turin, Italy.
[Simonato, Lorenzo] Univ Padua, Dept Environm Med & Publ Hlth, I-35100 Padua, Italy.
[Joeckel, Karl-Heinz] Univ Duisburg Essen, Inst Med Informat, Essen, Germany.
[Ahrens, Wolfgang; Pohlabeln, Hermann] Bremen Inst Prevent Res & Social Med, Bremen, Germany.
[Tardon, Adonina] Univ Oviedo, CIBERESP, Oviedo, Spain.
[Zaridze, David] Russian Canc Res Ctr, Moscow, Russia.
[Field, John] Univ Liverpool, Roy Castle Lung Canc Res Programme, Canc Res Ctr, Liverpool L69 3BX, Merseyside, England.
['t Mannetje, Andrea; Pearce, Neil] Massey Univ, Ctr Publ Hlth Res, Wellington, New Zealand.
[McLaughlin, John; Demers, Paul] Occupat Canc Res Ctr, Toronto, ON, Canada.
[Szeszenia-Dabrowska, Neonila] Nofer Inst Occupat Med, Lodz, Poland.
[Lissowska, Jolanta] M Sklodowska Curie Canc Ctr, Warsaw, Poland.
[Lissowska, Jolanta] Inst Oncol, Warsaw, Poland.
[Rudnai, Peter] Natl Inst Environm Hlth, Budapest, Hungary.
[Fabianova, Eleonora] Reg Author Publ Hlth, Banska Bystrica, Slovakia.
[Dumitru, Rodica Stanescu] Inst Publ Hlth, Bucharest, Romania.
[Bencko, Vladimir] Charles Univ Prague, Inst Hyg & Epidemiol, Fac Med 1, Prague, Czech Republic.
[Foretova, Lenka] Masaryk Mem Canc Inst, Brno, Czech Republic.
[Janout, Vladimir] Palacky Univ, Fac Med, CR-77147 Olomouc, Czech Republic.
[Boffetta, Paolo] Icahn Sch Med Mt Sinai, Tisch Canc Inst, New York, NY 10029 USA.
[Boffetta, Paolo] Icahn Sch Med Mt Sinai, Inst Translat Epidemiol, New York, NY 10029 USA.
[Forastiere, Francesco] ASL RomaE, Dept Epidemiol, Rome, Italy.
[Bueno-de-Mesquita, Bas] Natl Inst Publ Hlth & Environm Protect RIVM, Bilthoven, Netherlands.
[Peters, Susan; Vermeulen, Roel; Kromhout, Hans] Inst Risk Assessment Sci, Utrecht, Netherlands.
[Peters, Susan] Univ Western Australia, Sch Populat Hlth, Perth, WA 6009, Australia.
RP Bigert, C (reprint author), Karolinska Inst, Inst Environm Med, Solnavagen 4 10th Floor, SE-11365 Stockholm, Sweden.
EM carolina.bigert@ki.se
RI Yu, Ignatius Tak Sun/A-9936-2008; Szeszenia-Dabrowska,
Neonila/F-7190-2010; Janout, Vladimir/M-5133-2014; Bruning,
Thomas/G-8120-2015; Forastiere, Francesco/J-9067-2016; Vermeulen,
Roel/F-8037-2011;
OI pesatori, angela/0000-0002-0261-3252; Ahrens,
Wolfgang/0000-0003-3777-570X; Bruning, Thomas/0000-0001-9560-5464;
Forastiere, Francesco/0000-0002-9162-5684; Vermeulen,
Roel/0000-0003-4082-8163; Field, John/0000-0003-3951-6365
FU AFA Insurance in Sweden; German Social Accident Insurance (DGUV);
Canadian Institutes for Health Research and Guzzo-SRC Chair in
Environment and Cancer; National Cancer Institute of Canada; Canadian
Cancer Society; Cancer Care Ontario; French agency of health security
(ANSES); Fondation de France; French National Research Agency (ANR);
National Institute of Cancer (INCA); Fondation for Medical Research
(FRM); French Institute for Public Health Surveillance (InVS); Health
Ministry (DGS); Organization for the Research on Cancer (ARC); French
Ministry; Federal Ministry of Education, Science, Research, and
Technology; Federal Ministry of Science; Ministry of Labour and Social
Affairs; European Commission's INCO-COPERNICUS program; Polish State
Committee for Scientific Research grant; Roy Castle Foundation as part
of the Liverpool Lung Project; Intramural Research Program of the
National Institutes of Health, National Cancer Institute, Division of
Cancer Epidemiology and Genetics, Bethesda, MD, USA; Environmental
Epidemiology Program of the Lombardy Region, Italy; Istituto Nazionale
per l'Assicurazione contro gli Infortuni sul Lavoro, Rome, Italy;
Italian Association for Cancer Research, Region Piedmont, Compagnia di
San Paolo; European Union Nuclear Fission Safety Program; Lazio Region;
Dutch Ministry of Health, Welfare Sports; National Institute of Public
Health & the Environment; Europe Against Cancer Program; Instituto
Universitario de Oncologia, Universidad de Oviedo, Asturias; Fondo de
Investigacion Sanitaria (FIS); Ciber de Epidemiologia y Salud Publica
(CIBERESP), Spain; Research Grants Council of the Hong Kong Special
Administrative Region, China; Health Research Council of New Zealand;
New Zealand Department of Labour, Lottery Health Research; Cancer
Society of New Zealand; Swedish Council for Work Life Research; Swedish
EPA
FX This study was funded by the AFA Insurance in Sweden. The AFA Insurance
is owned by Sweden's labor market parties: the Confederation of Swedish
Enterprise, the Swedish Trade Union Confederation, and the Council for
Negotiation and Co-operation. The SYNERGY project is funded by the
German Social Accident Insurance (DGUV). The original studies were
funded by a list of agencies including the Canadian Institutes for
Health Research and Guzzo-SRC Chair in Environment and Cancer, the
National Cancer Institute of Canada with funds provided by the Canadian
Cancer Society and Cancer Care Ontario; the French agency of health
security (ANSES), the Fondation de France, the French National Research
Agency (ANR), the National Institute of Cancer (INCA), the Fondation for
Medical Research (FRM), the French Institute for Public Health
Surveillance (InVS), the Health Ministry (DGS), the Organization for the
Research on Cancer (ARC), and the French Ministry of work, solidarity
and public function (DGT). In Germany, the studies were funded by the
Federal Ministry of Education, Science, Research, and Technology grant
no. and the Federal Ministry of Science and the Ministry of Labour and
Social Affairs. The INCO study was supported by a grant from the
European Commission's INCO-COPERNICUS program, a grant from the Polish
State Committee for Scientific Research grant and the Roy Castle
Foundation as part of the Liverpool Lung Project. The EAGLE study was
funded by the Intramural Research Program of the National Institutes of
Health, National Cancer Institute, Division of Cancer Epidemiology and
Genetics, Bethesda, MD, USA; the Environmental Epidemiology Program of
the Lombardy Region, Italy; and the Istituto Nazionale per
l'Assicurazione contro gli Infortuni sul Lavoro, Rome, Italy. The TURIN
study was supported by the Italian Association for Cancer Research,
Region Piedmont, Compagnia di San Paolo. The study in Rome was conducted
with a partial support from the European Union Nuclear Fission Safety
Program and from the Lazio Region. The MORGEN study was supported by the
Dutch Ministry of Health, Welfare & Sports, National Institute of Public
Health & the Environment, and the Europe Against Cancer Program. The
CAPUA study was supported by the Instituto Universitario de Oncologia,
Universidad de Oviedo, Asturias, the Fondo de Investigacion Sanitaria
(FIS), and the Ciber de Epidemiologia y Salud Publica (CIBERESP), Spain.
The Hong Kong study was supported by a grant from the Research Grants
Council of the Hong Kong Special Administrative Region, China. The OCANZ
study was funded by the Health Research Council of New Zealand, the New
Zealand Department of Labour, Lottery Health Research, and by the Cancer
Society of New Zealand. The Swedish study LUCAS was supported by the
Swedish Council for Work Life Research and the Swedish EPA.
NR 40
TC 1
Z9 1
U1 4
U2 14
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1076-2752
EI 1536-5948
J9 J OCCUP ENVIRON MED
JI J. Occup. Environ. Med.
PD FEB
PY 2015
VL 57
IS 2
BP 202
EP 209
DI 10.1097/JOM.0000000000000337
PG 8
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA CB2VO
UT WOS:000349486700017
PM 25654522
ER
PT J
AU Chandler, JC
Sutherland, MD
Harton, MR
Molins, CR
Anderson, RV
Heaslip, DG
Bosio, CM
Belisle, JT
AF Chandler, Jeffrey C.
Sutherland, Marjorie D.
Harton, Marisa R.
Molins, Claudia R.
Anderson, Rebecca V.
Heaslip, Darragh G.
Bosio, Catharine M.
Belisle, John T.
TI Francisella tularensis LVS Surface and Membrane Proteins as Targets of
Effective Post-Exposure Immunization for Tularemia
SO JOURNAL OF PROTEOME RESEARCH
LA English
DT Article
DE Francisella tularensis; surface proteome; membrane proteome; adaptive
immunity; antibodies
ID CULTURE FILTRATE PROTEINS; LIVE VACCINE STRAIN; VIRULENT TYPE-A;
PROTEOMIC ANALYSIS; ANTIBODY-RESPONSE; IMMUNOREACTIVE ANTIGENS;
RESPIRATORY CHALLENGE; STATISTICAL-MODEL; MASS-SPECTROMETRY; ENRICHED
FRACTION
AB Francisella tularensis causes disease (tularemia) in a large number of mammals, including man. We previously demonstrated enhanced efficacy of conventional antibiotic therapy for tularemia by postexposure passive transfer of immune sera developed against a F. tularensis LVS membrane protein fraction (MPF). However, the protein composition of this immunogenic fraction was not defined. Proteomic approaches were applied to define the protein composition and identify the immunogens of MPF. MPF consisted of at least 299 proteins and 2-D Western blot analyses using sera from MPF-immunized and F. tularensis LVS-vaccinated mice coupled to liquid chromatography-tandem mass spectrometry identified 24 immunoreactive protein spots containing 45 proteins. A reverse vaccinology approach that applied labeling of F. tularensis LVS surface proteins and bioinformatics was used to reduce the complexity of potential target immunogens. Bioinformatics analyses of the immunoreactive proteins reduced the number of immunogen targets to 32. Direct surface labeling of F. tularensis LVS resulted in the identification of 31 surface proteins. However, only 13 of these were reactive with MPF and/or F. tularensis LVS immune sera. Collectively, this use of orthogonal proteomic approaches reduced the complexity of potential immunogens in MPF by 96% and allowed for prioritization of target immunogens for antibody-based immunotherapies against tularemia.
C1 [Chandler, Jeffrey C.; Sutherland, Marjorie D.; Harton, Marisa R.; Heaslip, Darragh G.; Belisle, John T.] Colorado State Univ, Dept Microbiol Immunol & Pathol, Rocky Mt Reg Ctr Excellence Biodef & Emerging Inf, Ft Collins, CO 80523 USA.
[Molins, Claudia R.] Ctr Dis Control & Prevent, Div Vector Borne Dis, Ft Collins, CO 80521 USA.
[Anderson, Rebecca V.; Bosio, Catharine M.] NIAID, Rocky Mt Lab, NIH, Hamilton, MT 59840 USA.
RP Belisle, JT (reprint author), Colorado State Univ, Dept Microbiol Immunol & Pathol, Rocky Mt Reg Ctr Excellence Biodef & Emerging Inf, Campus Delivery 0922, Ft Collins, CO 80523 USA.
EM John.Belisle@colostate.edu
RI Bosio, Catharine/D-7456-2015; Belisle, John/B-8944-2017
OI Belisle, John/0000-0002-2539-2798
FU National Institutes of Health, National Institute of Allergy and
Infectious Diseases [U54 AI-065357]
FX This research was supported by National Institutes of Health, National
Institute of Allergy and Infectious Diseases grant: U54 AI-065357.
NR 52
TC 1
Z9 1
U1 0
U2 6
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1535-3893
EI 1535-3907
J9 J PROTEOME RES
JI J. Proteome Res.
PD FEB
PY 2015
VL 14
IS 2
BP 664
EP 675
DI 10.1021/pr500628k
PG 12
WC Biochemical Research Methods
SC Biochemistry & Molecular Biology
GA CA9WV
UT WOS:000349276400008
PM 25494920
ER
PT J
AU Luckenbaugh, DA
Ameli, R
Brutsche, NE
Zarate, CA
AF Luckenbaugh, David A.
Ameli, Rezvan
Brutsche, Nancy E.
Zarate, Carlos A., Jr.
TI Rating depression over brief time intervals with the Hamilton Depression
Rating Scale: Standard vs. abbreviated scales
SO JOURNAL OF PSYCHIATRIC RESEARCH
LA English
DT Article
DE Antidepressant; Bipolar disorder; Depression; HDRS; Ketamine; Ratings
ID D-ASPARTATE ANTAGONIST; ADD-ON TRIAL; BIPOLAR DEPRESSION; REMISSION;
ANTIDEPRESSANTS; SENSITIVITY; SUBSCALES; SEVERITY; PLACEBO; METAANALYSIS
AB Although antidepressant trials typically use weekly ratings to examine changes in symptoms over six to 12 weeks, antidepressant treatments may improve symptoms more quickly. Thus, rating scales must be adapted to capture changes over shorter intervals. We examined the use of the 17-item Hamilton Depression Rating Scale (HDRS) to evaluate more rapid changes. Data were examined from 58 patients with major depressive disorder or bipolar disorder enrolled in double-blind, placebo-controlled, crossover studies who received a single infusion of ketamine (0.5 mg/kg) or placebo over 40 min then crossed over to the other condition. HDRS subscales, a single HDRS Depressed mood item, and a visual analogue scale were used at baseline, after a brief interval (230 min), and one week post-infusion. Effect sizes for the ketamine-placebo difference were moderate (d > 0.50), but one and two-item HDRS subscales had the smallest effects. Response rates on active drug were lowest for the complete HDRS (43%); the remaining scales had higher response rates to active drug, but the shortest subscales had higher response rates to placebo. Correlations between the changes from baseline to 230 min post-ketamine across scores were similar for most subscales (r = 0.82-0.97), but correlations using the single items were lower (r < 0.74). Overall, effect sizes for drug-placebo differences and correlations between changes were lower for one- and two-item measures. Response rates were lower with the full HDRS scale. The data suggest that, to best identify rapid antidepressant effects, a scale should have more than two items, but fewer items than a full scale. Published by Elsevier Ltd.
C1 NIMH, Expt Therapeut & Pathophysiol Branch, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
Dept Hlth & Human Serv, Bethesda, MD USA.
RP Zarate, CA (reprint author), NIMH, NIH, Expt Therapeut & Pathophysiol Branch, Clin Res Ctr, Bldg 10,10 Ctr Dr,Room 7-5342, Bethesda, MD 20892 USA.
EM dave.luckenbaugh@nih.gov; rezvan.ameli@nih.gov; nancy.brutsche@nih.gov;
zaratec@mail.nih.gov
FU Intramural NIH HHS [ZIA MH002857-10, ZIA MH002927-05]
NR 32
TC 3
Z9 3
U1 1
U2 3
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0022-3956
EI 1879-1379
J9 J PSYCHIATR RES
JI J. Psychiatr. Res.
PD FEB
PY 2015
VL 61
BP 40
EP 45
DI 10.1016/j.jpsychires.2014.12.015
PG 6
WC Psychiatry
SC Psychiatry
GA CB6IP
UT WOS:000349731000006
PM 25592045
ER
PT J
AU Liao, KP
Playford, MP
Frits, M
Coblyn, JS
Iannaccone, C
Weinblatt, ME
Shadick, NS
Mehta, NN
AF Liao, Katherine P.
Playford, Martin P.
Frits, Michelle
Coblyn, Jonathan S.
Iannaccone, Christine
Weinblatt, Michael E.
Shadick, Nancy S.
Mehta, Nehal N.
TI The Association Between Reduction in Inflammation and Changes in
Lipoprotein Levels and HDL Cholesterol Efflux Capacity in Rheumatoid
Arthritis
SO JOURNAL OF THE AMERICAN HEART ASSOCIATION
LA English
DT Article
DE inflammation; lipids; rheumatoid arthritis
ID C-REACTIVE PROTEIN; INCIDENT CARDIOVASCULAR EVENTS; NECROSIS FACTOR
THERAPY; MYOCARDIAL-INFARCTION; RESPONSE CRITERIA; LDL-CHOLESTEROL;
EUROPEAN-LEAGUE; STATIN THERAPY; LIPID PROFILE; RISK-FACTORS
AB Background-Potent anti-inflammatory rheumatoid arthritis (RA) treatments are associated with reduced cardiovascular risk as well as increases in low-density lipoprotein (LDL) cholesterol. This apparent paradox may be explained by favorable changes in other lipid measurements. The objective of this study was to determine the longitudinal association between changes in inflammation with advanced lipoprotein measurements and high-density lipoprotein (HDL) cholesterol efflux capacity.
Methods and Results-We conducted this study in a longitudinal RA cohort from a large academic center, including subjects with high-sensitivity C-reactive protein (hs-CRP) reduction >= 10 mg/L at 2 time points 1 year apart. Subjects receiving statins during the study period or preceding 6 months were excluded. We compared total cholesterol, LDL cholesterol, HDL cholesterol, apolipoprotein B, and apolipoprotein A1 levels and HDL cholesterol efflux capacity at baseline and 1-year follow-up by using the paired t test. We also assessed the correlations between reductions in hs-CRP with percentage change in lipid parameters. We studied 90 RA subjects (mean age 57 years, 89% female), all of whom were receiving disease-modifying antirheumatic drugs. We observed a 7.2% increase in LDL cholesterol levels (P= 0.02) and improvement in efflux capacity by 5.7% (P= 0.002) between baseline and follow-up, with a median hs-CRP reduction of 23.5 mg/L. We observed significant correlations between reductions in hs-CRP with increases in apolipoprotein A1 (r= 0.27, P= 0.01) and HDL cholesterol efflux capacity (r= 0.24, P= 0.02).
Conclusion-Among RA subjects experiencing reductions in hs-CRP, we observed increased LDL cholesterol levels and concomitant improvements in HDL cholesterol efflux capacity. These findings provide further insight into lipid modulation and the beneficial effect of reduction in inflammation on lipids in vivo.
C1 [Liao, Katherine P.; Frits, Michelle; Coblyn, Jonathan S.; Iannaccone, Christine; Weinblatt, Michael E.; Shadick, Nancy S.] Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA.
[Playford, Martin P.; Mehta, Nehal N.] NIH, Heart Blood & Lung Inst, Bethesda, MD 20892 USA.
RP Liao, KP (reprint author), Brigham & Womens Hosp, Div Rheumatol Immunol & Allergy, 75 Francis St,PBB B3, Boston, MA 02115 USA.
EM kliao@partners.org
FU National Institutes of Health (NIH) [K08 AR060257]; Harold and Duval
Bowen Fund; Division of Intramural Research at the NIH [HL-Z-0000]
FX Dr Liao is supported by National Institutes of Health (NIH) grant K08
AR060257 and the Harold and Duval Bowen Fund. Dr Mehta is funded by
grant HL-Z-0000 from the Division of Intramural Research at the NIH.
NR 48
TC 10
Z9 10
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 2047-9980
J9 J AM HEART ASSOC
JI J. Am. Heart Assoc.
PD FEB
PY 2015
VL 4
IS 2
AR e001588
DI 10.1161/JAHA.114.001588
PG 7
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA CB5LG
UT WOS:000349668000017
ER
PT J
AU Hart, PC
Mao, M
de Abreu, ALP
Ansenberger-Fricano, K
Ekoue, DN
Ganini, D
Kajdacsy-Balla, A
Diamond, AM
Minshall, RD
Consolaro, MEL
Santos, JH
Bonini, MG
AF Hart, Peter C.
Mao, Mao
de Abreu, Andre Luelsdorf P.
Ansenberger-Fricano, Kristine
Ekoue, Dede N.
Ganini, Douglas
Kajdacsy-Balla, Andre
Diamond, Alan M.
Minshall, Richard D.
Consolaro, Marcia E. L.
Santos, Janine H.
Bonini, Marcelo G.
TI MnSOD upregulation sustains the Warburg effect via mitochondrial ROS and
AMPK-dependent signalling in cancer
SO NATURE COMMUNICATIONS
LA English
DT Article
ID MANGANESE SUPEROXIDE-DISMUTASE; ACTIVATED PROTEIN-KINASE;
HYPOXIA-INDUCIBLE FACTOR; CELL-CYCLE PROGRESSION; BREAST-CANCER;
EPITHELIAL-CELLS; PROSTATE-CANCER; INHIBIT APOPTOSIS; INITIATING CELLS;
OXIDATIVE STRESS
AB Manganese superoxide dismutase (MnSOD/SOD2) is a mitochondria-resident enzyme that governs the types of reactive oxygen species egressing from the organelle to affect cellular signalling. Here we demonstrate that MnSOD upregulation in cancer cells establishes a steady flow of H2O2 originating from mitochondria that sustains AMP-activated kinase (AMPK) activation and the metabolic shift to glycolysis. Restricting MnSOD expression or inhibiting AMPK suppresses the metabolic switch and dampens the viability of transformed cells indicating that the MnSOD/AMPK axis is critical to support cancer cell bioenergetics. Recapitulating in vitro findings, clinical and epidemiologic analyses of MnSOD expression and AMPK activation indicated that the MnSOD/AMPK pathway is most active in advanced stage and aggressive breast cancer subtypes. Taken together, our results indicate that MnSOD serves as a biomarker of cancer progression and acts as critical regulator of tumour cell metabolism.
C1 [Hart, Peter C.; Mao, Mao; de Abreu, Andre Luelsdorf P.; Ansenberger-Fricano, Kristine; Bonini, Marcelo G.] Univ Illinois, Dept Med, Chicago, IL 60612 USA.
[Hart, Peter C.; Ekoue, Dede N.; Kajdacsy-Balla, Andre; Diamond, Alan M.; Bonini, Marcelo G.] Univ Illinois, Dept Pathol, Chicago, IL 60612 USA.
[Mao, Mao; de Abreu, Andre Luelsdorf P.; Ansenberger-Fricano, Kristine; Minshall, Richard D.; Bonini, Marcelo G.] Univ Illinois, Dept Pharmacol, Chicago, IL 60612 USA.
[de Abreu, Andre Luelsdorf P.; Consolaro, Marcia E. L.] Univ Estadual Maringa, BR-87020900 Maringa, Parana, Brazil.
[Ganini, Douglas] NIEHS, Free Radical Metabolite Sect, Lab Toxicol & Pharmacol, NIH, Res Triangle Pk, NC 27709 USA.
[Minshall, Richard D.] Univ Illinois, Dept Anesthesiol, Chicago, IL 60612 USA.
[Santos, Janine H.] Univ Med & Dent New Jersey, Dept Physiol & Pharmacol, Newark, NJ 07103 USA.
RP Bonini, MG (reprint author), Univ Illinois, Dept Med, 909 South Wolcott Ave,COMRB 1131, Chicago, IL 60612 USA.
EM mbonini@uic.edu
RI Mao, Mao/E-3783-2013; Consolaro, Marcia/I-4932-2014;
OI Mao, Mao/0000-0003-1524-8853; Consolaro, Marcia/0000-0001-9102-4865;
Hart, Peter/0000-0003-1843-9102
FU US Department of Defense (ARO) [61758-LS]; NCRR/NIH [S10RR027848]; NIH
[HL072742, P01 HL60678]; CAPES-Coordenacao de Aperfeicoamento Pessoal,
Ministerio da Ciencia e Tecnologia/Brazil [RO1 CA101053, A109/2013];
[1R21CA182103-01]
FX We are indebted to Drs Larry W. Oberley (in memoriam) and Frederick
Domann (University of Iowa) for the generous gift of cell lines stably
overexpressing MnSOD, Dr Kevin P. Claffey (University of Connecticut)
for the generous gift of MCF-7-AMPKa1 -/- cells, Dr Kevin Struhl
(Harvard University) for the gift of the MCF10A lines expressing v-Src
under ER induction, Patricia Mavrogianis, Andrew Hall and Emily Ionetz
at the Research Histology Core at the University of Illinois at Chicago
for providing histology services, Dr Soumen Bera, Emmanuel Ansong, Paula
Green, Alyssa Master and M. Saqib Baig for technical assistance, and for
funding provided by the US Department of Defense (ARO no. 61758-LS) to
M.G.B, the NCRR/NIH (S10RR027848) to M.G.B., 1R21CA182103-01 to A.M.D.
and M.G.B. K.A.-F. and P.C.H. were supported by NIH T32 (HL072742). We
also acknowledge gifts from RO1 CA101053 to A.M.D., NIH P01 HL60678 to
R.D.M., CAPES-Coordenacao de Aperfeicoamento Pessoal, Ministerio da
Ciencia e Tecnologia/Brazil-A109/2013 to M.G.B. and M.E.L.C.
NR 70
TC 29
Z9 29
U1 4
U2 22
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 FEB
PY 2015
VL 6
AR 6053
DI 10.1038/ncomms7053
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CC0OO
UT WOS:000350035500001
PM 25651975
ER
PT J
AU Radke, AK
Zlebnik, NE
Carroll, ME
AF Radke, Anna K.
Zlebnik, Natalie E.
Carroll, Marilyn E.
TI Cocaine withdrawal in rats selectively bred for low (LoS) versus high
(HiS) saccharin intake
SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR
LA English
DT Article
DE Cocaine; Rat; Motivation; Sweet preference; Selective breeding;
Withdrawal
ID OPIATE WITHDRAWAL; NUCLEUS-ACCUMBENS; SUCROSE SOLUTION; TASTE;
ABSTINENCE; SCHEDULE; ESCALATION; PREFERENCE; ADDICTION; NICOTINE
AB Cocaine use results in anhedonia during withdrawal, but it is not clear how this emotional state interacts with an individual's vulnerability for addiction. Rats selectively bred for high (HiS) or low (LoS) saccharin intake are a well-established model of drug abuse vulnerability, with HiS rats being more likely to consume sweets and drugs of abuse such as cocaine and heroin (Carroll et al., 2002) than LoS rats. This study examined whether the motivational consequences of cocaine withdrawal are differentially expressed in HiS and LoS rats. HiS and LoS rats were trained to respond for a sucrose reward on a progressive ratio (PR) schedule of reinforcement and breakpoints were measured during and after chronic, continuous exposure to cocaine (30 mg/kg/day). Cocaine, but not saline, treatment resulted in lower breakpoints for sucrose during withdrawal in LoS rats only. These results suggest anhedonia during withdrawal is more pronounced in the less vulnerable LoS rats. Fewer motivational deficits during withdrawal may contribute to greater drug vulnerability in the HiS line. Published by Elsevier Inc.
C1 [Radke, Anna K.; Zlebnik, Natalie E.; Carroll, Marilyn E.] Univ Minnesota, Dept Psychiat, Minneapolis, MN 55455 USA.
RP Radke, AK (reprint author), NIAAA, NIH, 5625 Fishers Lane, Rockville, MD 20852 USA.
EM anna.radke@nih.gov
FU NIDA [K05 DA015267, R01 DA003240, P20 DA024196]
FX This work was funded by NIDA grants K05 DA015267, R01 DA003240, and P20
DA024196 (MEC).
NR 43
TC 3
Z9 3
U1 4
U2 5
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 FEB
PY 2015
VL 129
BP 51
EP 55
DI 10.1016/j.pbb.2014.11.022
PG 5
WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy
SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy
GA CB4HD
UT WOS:000349587900008
PM 25482327
ER
PT J
AU Patel, N
Grillon, C
Pavletic, N
Rosen, D
Pine, DS
Ernst, M
AF Patel, Nilam
Grillon, Christian
Pavletic, Nevia
Rosen, Dana
Pine, Daniel S.
Ernst, Monique
TI Oxytocin and vasopressin modulate risk-taking
SO PHYSIOLOGY & BEHAVIOR
LA English
DT Article
DE Neuropeptides; Motivated behavior; Social stress; Sex; Risk-valence
ID MEDIAL PREFRONTAL CORTEX; GENDER-DIFFERENCES; DECISION-MAKING; HUMANS;
BEHAVIOR; ANXIETY; STRESS; BRAIN; CIRCUITRY; WOMEN
AB The modulation of risk-taking is critical for adaptive and optimal behavior. This study examined how oxytocin (OT) and arginine vasopressin (AVP) influence risk-taking in function of three parameters: sex, risk-valence, and social context. Twenty-nine healthy adults (14 males) completed a risk-taking task, the Stunt task, both in a social-stress (evaluation by unfamiliar peers) and non-social context, in three separate drug treatment sessions. During each session, one of three drugs, OT, AVP, or placebo (PLC), was administered intra-nasally. OT and AVP relative to PLC reduced betting-rate (risk-averse effect). This risk-averse effect was further qualified: AVP reduced risk-taking in the positive risk-valence (high win-probability), and regardless of social context or sex. In contrast, OT reduced risk-taking in the negative risk-valence (low win-probability), and only in the social-stress context and men. The reduction in risk-taking might serve a role in defensive behavior. These findings extend the role of these neuromodulators to behaviors beyond the social realm. How the behavioral modulation of risk-taking maps onto the function of the neural targets of OT and AVP may be the next step in this line of research. Published by Elsevier Inc.
C1 [Patel, Nilam] Amer Univ, Dept Psychol, Washington, DC 20016 USA.
[Patel, Nilam; Grillon, Christian; Pavletic, Nevia; Rosen, Dana; Pine, Daniel S.; Ernst, Monique] NIMH, NIH, Bethesda, MD 20892 USA.
RP Ernst, M (reprint author), NIMH, NIH, 15K North Dr,MSC 2670, Bethesda, MD 20892 USA.
EM emstm@mail.nih.gov
FU National Institute of Mental Health [MH002798]
FX This study was funded by the Intramural Research Program of the National
Institute of Mental Health (Grant number MH002798). Dr. Pine has
received compensation for activities related to teaching, editing, and
clinical care that pose no conflicts of interest. The authors declare no
conflict of interest.
NR 35
TC 7
Z9 7
U1 1
U2 24
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0031-9384
J9 PHYSIOL BEHAV
JI Physiol. Behav.
PD FEB
PY 2015
VL 139
BP 254
EP 260
DI 10.1016/j.physbeh.2014.11.018
PG 7
WC Psychology, Biological; Behavioral Sciences
SC Psychology; Behavioral Sciences
GA CB4BY
UT WOS:000349574400035
PM 25446228
ER
PT J
AU Vega-Sanchez, R
Arenas-Hernandez, M
Vazquez-Perez, JA
Moreno-Valencia, Y
Gomez-Lopez, N
AF Vega-Sanchez, R.
Arenas-Hernandez, M.
Vazquez-Perez, J. A.
Moreno-Valencia, Y.
Gomez-Lopez, N.
TI Evaluation of reference genes for expression studies in leukocytes from
term human pregnancy
SO PLACENTA
LA English
DT Article
DE Pregnancy; Labor; Leukocytes; Housekeeping genes; Stability; geNorm
ID 18S RIBOSOMAL-RNA; REAL-TIME PCR; HOUSEKEEPING GENES; SELECTION;
VALIDATION; STABILITY; TISSUES; LABOR
AB Introduction: Human labor is considered an inflammatory process modulated by systemic and local leukocytes that infiltrate into the maternal fetal interface. The putative roles of these leukocytes are currently being studied with gene expression assays. Such assays are normalized by the expression of housekeeping genes. However, expression of housekeeping genes may vary depending on the cell type and/or the experimental conditions. The aim of this study was to analyze the expression stability of several housekeeping genes in leukocytes from term human pregnancies, considering both anatomical origin and presence of labor.
Methods: We analyzed the gene expression of ACTB, B2M, GAPDH, GUSB, PGK1, RN18S1, TBP and UBC in leukocytes from maternal peripheral blood, placental blood and choriodecidua in women delivering at term with or without the presence of labor through real-time qPCR. Then we used geNorm to evaluate expression stability and pairwise variation.
Results: The expression of all tested genes showed to be stable independent of the anatomical compartment and the absence or presence of labor. However, PGK1, GUSB and TBP showed to be the most stable and RN18S1 the least stable. Pairwise variation analyses showed that only two genes are needed for normalization yet the inclusion of a third improves its accuracy.
Discussion: PGK1, GUSB and TBP are the most adequate reference genes for gene expression normalization in leukocytes from term pregnancies, regardless of their anatomical origin (maternal peripheral blood, placental blood or choriodecidua) or the presence or absence of labor. Our study is the first report on housekeeping gene stability in leukocytes from healthy pregnant women. (C) 2014 Elsevier Ltd. All rights reserved.
C1 [Vega-Sanchez, R.] Inst Nacl Perinatol, Dept Nutr & Bioprogramming, Mexico City 11000, DF, Mexico.
[Arenas-Hernandez, M.; Gomez-Lopez, N.] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA.
[Arenas-Hernandez, M.] Inst Politecn Nacl, Natl Sch Biol Sci, Mexico City, DF, Mexico.
[Vazquez-Perez, J. A.; Moreno-Valencia, Y.] Inst Nacl Enfermedades Resp, Dept Virol & Mycol Res, Mexico City 14080, DF, Mexico.
[Gomez-Lopez, N.] Wayne State Univ, CS Mott Ctr Human Growth & Dev, Dept Obstet & Gynecol, Perinatol Res Branch,NICHD,NIH,Sch Med, Detroit, MI 48201 USA.
RP Vega-Sanchez, R (reprint author), Inst Nacl Perinatol, Dept Nutr & Bioprogramming, Montes Urales 800, Mexico City 11000, DF, Mexico.
EM r.vega@inper.mx; marenash@med.wayne.edu; joevazpe@gmail.com;
yazmin258@gmail.com; ngomezlo@med.wayne.edu
RI Gomez-Lopez, Nardhy/R-7664-2016
OI Gomez-Lopez, Nardhy/0000-0002-3406-5262
FU CONACYT, Mexico [SALUD-2010-01-141144]; Wayne State University Perinatal
Initiative in Maternal, Perinatal and Child Health, Eunice Kennedy
Shriver National Institute of Child Health and Human Development of the
National Institutes of Health (NICHD/NIH)
FX This study was supported by grant SALUD-2010-01-141144 from CONACYT,
Mexico. N.G-L is funded by Wayne State University Perinatal Initiative
in Maternal, Perinatal and Child Health, Eunice Kennedy Shriver National
Institute of Child Health and Human Development of the National
Institutes of Health (NICHD/NIH).
NR 20
TC 2
Z9 2
U1 0
U2 5
PU W B SAUNDERS CO LTD
PI LONDON
PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND
SN 0143-4004
EI 1532-3102
J9 PLACENTA
JI Placenta
PD FEB
PY 2015
VL 36
IS 2
BP 240
EP 245
DI 10.1016/j.placenta.2014.11.010
PG 6
WC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology
SC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology
GA CB4FH
UT WOS:000349583100020
PM 25484264
ER
PT J
AU Green, M
Covington, S
Taranto, S
Wolfe, C
Bell, W
Biggins, SW
Conti, D
DeStefano, GD
Dominguez, E
Ennis, D
Gross, T
Klassen-Fischer, M
Kotton, C
LaPointe-Rudow, D
Law, Y
Ludrosky, K
Menegus, M
Morris, MI
Nalesnik, MA
Pavlakis, M
Pruett, T
Sifri, C
Kaul, D
AF Green, Michael
Covington, Shandie
Taranto, Sarah
Wolfe, Cameron
Bell, Walter
Biggins, Scott W.
Conti, David
DeStefano, G. David
Dominguez, Edward
Ennis, Donna
Gross, Thomas
Klassen-Fischer, Mary
Kotton, Camille
LaPointe-Rudow, Dianne
Law, Yuk
Ludrosky, Kristen
Menegus, Marilyn
Morris, Michele I.
Nalesnik, Michael A.
Pavlakis, Martha
Pruett, Timothy
Sifri, Costi
Kaul, Daniel
TI Donor-Derived Transmission Events in 2013: A Report of the Organ
Procurement Transplant Network Ad Hoc Disease Transmission Advisory
Committee
SO TRANSPLANTATION
LA English
DT Article
AB Background. The Organ Procurement Transplant Network Disease Transmission Advisory Committee (DTAC), a multidisciplinary committee, evaluates potential donor-derived transmission events (PDDTE), including infections andmalignancies, to assess for donor transmitted events. Methods. Reports of unexpected PDDTE to Organ Procurement Transplant Network in 2013 were fully reviewed by DTAC. A standardized algorithm was used to assess each PDDTE from a given donor and to classify each individual recipient from that donor. Results. Of 443 total PDDTE submitted, 159 were triaged and not sent out to the full DTAC. Of 284 fully evaluated reports, 32 (11.3%) resulted in a proven/probable (P/P) transmission of infection, malignancy or other conditions to 42 recipients. Of 204 infection events, 24 were classified as P/P affecting 30 recipients, with four deaths. Bacteria were the most frequently reported type of infection, accounting for 99 reports but only 12 recipients from 11 donors experienced P/P transmission. There were 65 donors reported with potential malignancy events and 5 were classified as P/P transmissions with 8 affected recipients and 2 deaths. Additionally, there were 16 noninfection, nonmalignancy reports resulting in 3 P/P transmissions to 4 recipients and 1 death. Conclusions. There was a 43% increase in the number of PDDTE reported and reviewed in 2013 over 2012. However, the percent with P/P transmission remains low, affecting recipients from 32 donors especially when compared with the more than 14,000 donors recovered annually in the United States. The continued use of the new standard algorithm and triaging process will enhance the reproducibility of DTAC assessments and allow more robust analysis of our aggregate DTAC experience.
C1 [Green, Michael] Univ Pittsburgh, Med Ctr, Div Pediat Infect Dis, Pittsburgh, PA USA.
[Covington, Shandie; Taranto, Sarah] United Network Organ Sharing, Richmond, VA USA.
[Wolfe, Cameron] Duke Univ, Med Ctr, Div Transplant Infect Dis, Durham, NC USA.
[Bell, Walter] Univ Alabama Birmingham, Div Anat Pathol, Birmingham, AL USA.
[Biggins, Scott W.] Univ Colorado, Div Gastroenterol, Aurora, CO USA.
[Conti, David] Albany Med Coll, Dept Transplant Surg, Albany, NY 12208 USA.
[DeStefano, G. David] Lifesharing, San Diego, CA USA.
[Dominguez, Edward] Methodist Dallas Med Ctr, Div Infect Dis, Dallas, TX USA.
[Ennis, Donna] Indiana Univ Hosp, Indianapolis, IN 46202 USA.
[Gross, Thomas] NCI, Ctr Global Hlth, Rockville, MD USA.
[Klassen-Fischer, Mary] Joint Pathol Ctr, Silver Spring, MD USA.
[Kotton, Camille] Massachusetts Gen Hosp, Div Infect Dis, Boston, MA 02114 USA.
[LaPointe-Rudow, Dianne] Mt Sinai Med Ctr, New York, NY 10029 USA.
[Law, Yuk] Seattle Childrens Hosp, Div Cardiac Transplant, Seattle, WA USA.
[Ludrosky, Kristen] Cleveland Clin, Cleveland, OH 44106 USA.
[Menegus, Marilyn] Univ Rochester, Med Ctr, Dept Microbiol & Immunol, Rochester, NY 14642 USA.
[Morris, Michele I.] Univ Miami Hosp, Div Internal Med, Miami, FL USA.
[Nalesnik, Michael A.] Univ Pittsburgh, Med Ctr, Div Transplant Pathol, Pittsburgh, PA USA.
[Pavlakis, Martha] Beth Israel Deaconess Med Ctr, Div Nephrol, Boston, MA 02215 USA.
[Pruett, Timothy] Univ Minnesota, Med Ctr, Div Transplantat, Minneapolis, MN 55455 USA.
[Sifri, Costi] Univ Virginia Hlth Syst, Div Infect Dis, Charlottesville, VA USA.
[Kaul, Daniel] Univ Michigan, Med Ctr, Div Infect Dis, Ann Arbor, MI USA.
RP Green, M (reprint author), Univ Pittsburgh, Sch Med, Pittsburgh, PA 15260 USA.
EM Michael.green@chp.edu
FU Health Resources and Services Administration [234-2005-370011C]
FX This analysis of DTAC data was supported wholly or in part by Health
Resources and Services Administration contract 234-2005-370011C.
NR 2
TC 8
Z9 8
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0041-1337
EI 1534-6080
J9 TRANSPLANTATION
JI Transplantation
PD FEB
PY 2015
VL 99
IS 2
BP 282
EP 287
DI 10.1097/TP.0000000000000584
PG 6
WC Immunology; Surgery; Transplantation
SC Immunology; Surgery; Transplantation
GA CB2YH
UT WOS:000349493900016
PM 25594557
ER
PT J
AU Bai, P
Nagy, L
Fodor, T
Liaudet, L
Pacher, P
AF Bai, Peter
Nagy, Lille
Fodor, Tamas
Liaudet, Lucas
Pacher, Pal
TI Poly(ADP-ribose) polymerases as modulators of mitochondrial activity
SO TRENDS IN ENDOCRINOLOGY AND METABOLISM
LA English
DT Review
DE poly(ADP-ribose) polymerase; NAD(+); AMP activated kinase; Sirtuin;
hypoxia-inducible factor; nuclear respiratory factor
ID INDUCIBLE FACTOR-I; OXIDATIVE STRESS; SKELETAL-MUSCLE; NITRIC-OXIDE;
CELL-DEATH; GLYCOHYDROLASE PARG; PARP-1; ACTIVATION; INHIBITION; SIRT1
AB Mitochondria are essential in cellular stress responses. Mitochondrial output to environmental stress is a major factor in metabolic adaptation and is regulated by a complex network of energy and nutrient sensing proteins. Activation of poly(ADP-ribose) polymerases (PARPs) has been known to impair mitochondrial function; however, our view of PARP-mediated mitochondrial dysfunction and injury has only recently fundamentally evolved. In this review, we examine our current understanding of PARP-elicited mitochondria! damage, PARP-mediated signal transduction pathways, transcription factors that interact with PARPs and govern mitochondrial biogenesis, as well as mitochondrial diseases that are mediated by PARPs. With PARP activation emerging as a common underlying mechanism in numerous pathologies, a better understanding the role of various PARPs in mitochondrial regulation may help open new therapeutic avenues.
C1 [Bai, Peter] Univ Debrecen, Res Ctr Mol Med, H-4012 Debrecen, Hungary.
[Bai, Peter; Nagy, Lille; Fodor, Tamas] MTA DE Lendulet Lab, Cellular Metab Res Grp, Debrecen, Hungary.
[Bai, Peter; Nagy, Lille; Fodor, Tamas] Univ Debrecen, Dept Med Chem, H-4012 Debrecen, Hungary.
[Liaudet, Lucas] Univ Lausanne Hosp, Med Ctr, Dept Intens Care Med, Lausanne, Switzerland.
[Liaudet, Lucas] Univ Lausanne Hosp, Med Ctr, Burn Ctr, Lausanne, Switzerland.
[Pacher, Pal] NIAAA, Lab Physiol Studies, Sect Oxidat Stress & Tissue Injury, NIH,DICBR, Bethesda, MD USA.
RP Bai, P (reprint author), Univ Debrecen, Res Ctr Mol Med, H-4012 Debrecen, Hungary.
EM baip@med.unideb.hu
RI Pacher, Pal/B-6378-2008; Liaudet, Lucas/E-1322-2017
OI Pacher, Pal/0000-0001-7036-8108; Liaudet, Lucas/0000-0003-2670-4930
FU Bolyai; Momentum fellowship of the Hungarian Academy of Sciences; OTKA
[K108308, K105872, TAMOP-4.2.2.A-11/1/KONV-2012-0025]; Intramural
Research Program of NIH/NIAAA
FX We would like to apologize to all the authors whose relevant work was
not cited due to the space limitations of this review. This work was
supported by Bolyai and the Momentum fellowship of the Hungarian Academy
of Sciences, by grants from OTKA (K108308, K105872),
TAMOP-4.2.2.A-11/1/KONV-2012-0025 to P.B., and by the Intramural
Research Program of NIH/NIAAA to P.P.
NR 87
TC 23
Z9 23
U1 1
U2 15
PU ELSEVIER SCIENCE LONDON
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 1043-2760
J9 TRENDS ENDOCRIN MET
JI Trends Endocrinol. Metab.
PD FEB
PY 2015
VL 26
IS 2
BP 75
EP 83
DI 10.1016/j.tem.2014.11.003
PG 9
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA CB6HZ
UT WOS:000349729400003
PM 25497347
ER
PT J
AU Dineley, KT
Pandya, AA
Yakel, JL
AF Dineley, Kelly T.
Pandya, Anshul A.
Yakel, Jerrel L.
TI Nicotinic ACh receptors as therapeutic targets in CNS disorders
SO TRENDS IN PHARMACOLOGICAL SCIENCES
LA English
DT Review
DE alpha 7 receptor; alpha 4 beta 2 receptor; nAChR; cys-loop receptor
ID POSITIVE ALLOSTERIC MODULATOR; BETA-AMYLOID PEPTIDE; ALZHEIMERS
ASSOCIATION WORKGROUPS; AUTISM SPECTRUM DISORDERS; HIPPOCAMPAL SYNAPTIC
PLASTICITY; MILD COGNITIVE IMPAIRMENT; PLACEBO-CONTROLLED TRIAL; BASAL
FOREBRAIN NEURONS; CENTRAL-NERVOUS-SYSTEM; PROOF-OF-CONCEPT
AB The neurotransmitter acetylcholine (ACh) can regulate neuronal excitability by acting on the cys-loop cation-conducting ligand-gated nicotinic ACh receptor (nAChR) channels. These receptors are widely distributed throughout the central nervous system (CNS), being expressed on neurons and non-neuronal cells, where they participate in a variety of physiological responses such as anxiety, the central processing of pain, food intake, nicotine seeking behavior, and cognitive functions. In the mammalian brain, nine different subunits have been found thus far, which assemble into pentameric complexes with much subunit diversity; however, the alpha 7 and alpha 4 beta 2 subtypes predominate in the CNS. Neuronal nAChR dysfunction is involved in the pathophysiology of many neurological disorders. Here we will briefly discuss the functional makeup and expression of the nAChRs in mammalian brain, and their role as targets in neurodegenerative diseases (in particular Alzheimer's disease, AD), neurodevelopmental disorders (in particular autism and schizophrenia), and neuropathic pain.
C1 [Dineley, Kelly T.] Univ Texas Med Branch, Mitchell Ctr Neurodegenerat Dis, Dept Neurol, Galveston, TX 77555 USA.
[Pandya, Anshul A.] Univ Alaska Fairbanks, Coll Rural & Community Dev, Dept Biosci, Kotzebue, AK 99752 USA.
[Yakel, Jerrel L.] NIEHS, Neurobiol Lab, NIH, DHHS, Res Triangle Pk, NC 27709 USA.
RP Yakel, JL (reprint author), NIEHS, Neurobiol Lab, NIH, DHHS, F2-08,POB 12233,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA.
EM yakel@niehs.nih.gov
FU Intramural Research Program, NIEHS/NIH; Independent Investigator
Research Grant from the Alzheimer's Association
FX This work was supported by the Intramural Research Program, NIEHS/NIH to
J.L.Y. and A.A.P., a kind gift to K.T.D. from J&W Mohn, and an
Independent Investigator Research Grant from the Alzheimer's Association
to K.T.D.
NR 192
TC 64
Z9 64
U1 11
U2 55
PU ELSEVIER SCIENCE LONDON
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0165-6147
J9 TRENDS PHARMACOL SCI
JI Trends Pharmacol. Sci.
PD FEB
PY 2015
VL 36
IS 2
BP 96
EP 108
DI 10.1016/j.tips.2014.12.002
PG 13
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA CB6HT
UT WOS:000349728800005
PM 25639674
ER
PT J
AU Brunoni, AR
Baeken, C
Machado-Vieira, R
Gattaz, WF
Vanderhasselt, MA
AF Brunoni, Andre R.
Baeken, Chris
Machado-Vieira, Rodrigo
Gattaz, Wagner F.
Vanderhasselt, Marie-Anne
TI BDNF blood levels after non-invasive brain stimulation interventions in
major depressive disorder: A systematic review and meta-analysis
SO WORLD JOURNAL OF BIOLOGICAL PSYCHIATRY
LA English
DT Article
DE non-invasive brain stimulation; brain-derived neurotrophic factor;
meta-analysis; major depressive disorder; neurotrophic factors
ID TRANSCRANIAL MAGNETIC STIMULATION; TREATMENT-RESISTANT DEPRESSION;
NEUROTROPHIC FACTOR; ELECTROCONVULSIVE-THERAPY; SYNAPTIC PLASTICITY;
HEALTHY-VOLUNTEERS; PREFRONTAL CORTEX; SERUM-LEVELS; DOUBLE-BLIND; RTMS
AB Objectives. To evaluate whether the antidepressant effects of novel non-invasive brain stimulation (NIBS) therapies are associated with neurotrophic effects, indexed by peripheral brain-derived neurotrophic factor (BDNF) levels. Methods. Systematic review and meta-analysis. We included trials published in PubMed/Medline from the first date available to June 2014 measuring BDNF blood levels before and after repetitive transcranial magnetic stimulation or transcranial direct current stimulation in depression. Results. Eight datasets (n = 259) were included. These studies enrolled mostly treatment-resistant depression patients, who received daily stimulation sessions on the left dorsolateral prefrontal cortex. BDNF did not increase after NIBS (Hedges' g = 0.03, 95% CI = -0.21 to 0.27), even when examining each intervention separately. Meta-regressions did not identify the influence of any clinical and demographic predictors on the outcome. Finally, Begg's funnel plot did not suggest publication bias and results were robust according to sensitivity analysis. Conclusions. Peripheral BDNF levels do not increase after NIBS in depression. Such biomarker might, therefore, not be suitable to index NIBS antidepressant response. Further trials are needed, particularly exploring non-medicated populations, performing subsequent BDNF assessments in a larger timeframe and employing more intensive NIBS treatment protocols.
C1 [Brunoni, Andre R.; Machado-Vieira, Rodrigo; Gattaz, Wagner F.] Univ Sao Paulo, Dept & Inst Psychiat, Lab Neurosci LIM27, Sao Paulo, Brazil.
[Brunoni, Andre R.] Univ Sao Paulo, Univ Hosp, Interdisciplinary Ctr Appl Neuromodulat & Clin CI, Sao Paulo, Brazil.
[Brunoni, Andre R.] Univ Sao Paulo, Univ Hosp, Epidemiol Res Ctr, Sao Paulo, Brazil.
[Brunoni, Andre R.] Univ Sao Paulo, Fac Med, Dept & Inst Psychiat, SIN, Sao Paulo, Brazil.
[Baeken, Chris] Univ Ghent, Dept Psychiat & Med Psychol, B-9000 Ghent, Belgium.
[Baeken, Chris] Univ Hosp UZBrussel, Dept Psychiat, Brussels, Belgium.
[Machado-Vieira, Rodrigo] NIMH, NIH, Intramural Res Program, Expt Therapeut & Pathophysiol Branch, Bethesda, MD 20892 USA.
[Vanderhasselt, Marie-Anne] Univ Ghent, Dept Expt Clin & Hlth Psychol, B-9000 Ghent, Belgium.
RP Brunoni, AR (reprint author), Dept & Inst Psychiatry, R Dr Ovidio Pires Campos 785,2nd floor, Sao Paulo, Brazil.
EM Brunoni@usp.br
RI MACHADO-VIEIRA, RODRIGO/D-8293-2012;
OI MACHADO-VIEIRA, RODRIGO/0000-0002-4830-1190; Russowsky Brunoni,
Andre/0000-0002-6310-3571
FU Brain & Behavior Research Foundation (NARSAD) [YI 2013]; Sao Paulo
Research State Foundation [FAPESP 2012/20911-5]; National Council for
Scientific and Technological Development (CNPq) [455157/2013-8];
AssociacaoBeneficenteAlzira Denise Hertzog da Silva (ABADHS); Ghent
University Multidisciplinary Research Partnership "The integrative
neuroscience of behavioral control"
FX MAV (FWO08/PDO/168) is a postdoctoral research fellow of the Research
Foundation Flanders (FWO). ARB receives Young Investigator grants from
the Brain & Behavior Research Foundation (NARSAD, YI 2013), Sao Paulo
Research State Foundation (FAPESP 2012/20911-5) and the National Council
for Scientific and Technological Development (CNPq, 455157/2013-8). "The
Laboratory of Neurosciences receives financial support from the
AssociacaoBeneficenteAlzira Denise Hertzog da Silva (ABADHS)". This work
was also supported by the Ghent University Multidisciplinary Research
Partnership "The integrative neuroscience of behavioral control". The
authors have no conflicts of interest to disclose.
NR 41
TC 5
Z9 5
U1 2
U2 11
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 FEB
PY 2015
VL 16
IS 2
BP 114
EP 122
DI 10.3109/15622975.2014.958101
PG 9
WC Psychiatry
SC Psychiatry
GA CB5LZ
UT WOS:000349670200005
PM 25264290
ER
PT J
AU Lountos, GT
Cherry, S
Tropea, JE
Waugh, DS
AF Lountos, George T.
Cherry, Scott
Tropea, Joseph E.
Waugh, David S.
TI Structural analysis of human dual-specificity phosphatase 22 complexed
with a phosphotyrosine-like substrate
SO ACTA CRYSTALLOGRAPHICA SECTION F-STRUCTURAL BIOLOGY COMMUNICATIONS
LA English
DT Article
DE dual-specificity phosphatase 22; 4-nitrophenyl phosphate
ID PROTEIN-TYROSINE PHOSPHATASES; JSP-1 INHIBITORS; RHODANINE DERIVATIVES;
CRYSTAL-STRUCTURE; CATALYTIC ROLE; TARGETS; CRYSTALLOGRAPHY; VHR;
PROBABILITIES; RECOGNITION
AB 4-Nitrophenyl phosphate (p-nitrophenyl phosphate, pNPP) is widely used as a small molecule phosphotyrosine-like substrate in activity assays for protein tyrosine phosphatases. It is a colorless substrate that upon hydrolysis is converted to a yellow 4-nitrophenolate ion that can be monitored by absorbance at 405 nm. Therefore, the pNPP assay has been widely adopted as a quick and simple method to assess phosphatase activity and is also commonly used in assays to screen for inhibitors. Here, the first crystal structure is presented of a dual-specificity phosphatase, human dual-specificity phosphatase 22 (DUSP22), in complex with pNPP. The structure illuminates the molecular basis for substrate binding and may also facilitate the structure-assisted development of DUSP22 inhibitors.
C1 [Lountos, George T.] Leidos Biomedical Res Inc, Basic Sci Program, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
[Lountos, George T.; Cherry, Scott; Tropea, Joseph E.; Waugh, David S.] NCI, Macromol Crystallog Lab, Ctr Canc Res, Ft Detrick, MD 21702 USA.
RP Waugh, DS (reprint author), NCI, Macromol Crystallog Lab, Ctr Canc Res, Ft Detrick, MD 21702 USA.
EM waughd@mail.nih.gov
FU Frederick National Laboratory for Cancer Research, National Institutes
of Health [HHSN261200800001E]; NIH, National Cancer Institute, Center
for Cancer Research; US Department of Energy, Office of Science, Office
of Basic Energy Sciences [W-31-109-Eng-38]
FX This project has been funded in whole or in part with Federal funds from
the Frederick National Laboratory for Cancer Research, National
Institutes of Health under contract HHSN261200800001E and the Intramural
Research Program of the NIH, National Cancer Institute, Center for
Cancer Research. The content of this publication does not necessarily
reflect the views or policies of the Department of Health and Human
Services, nor does the mention of trade names, commercial products or
organizations imply endorsement by the US Government. We thank the
Biophysics Resource in the Structural Biophysics Laboratory, NCI at
Frederick for use of the LC/ESMS instrument. X-ray diffraction data were
collected on the Southeast Regional Collaborative Access Team (SER-CAT)
beamline 22-BM of the Advanced Photon Source, Argonne National
Laboratory. Supporting institutions may be found at
http://www.ser-cat.org/members.html. Use of the Advanced Photon Source
was supported by the US Department of Energy, Office of Science, Office
of Basic Energy Sciences under contract No. W-31-109-Eng-38.
NR 47
TC 1
Z9 1
U1 1
U2 8
PU INT UNION CRYSTALLOGRAPHY
PI CHESTER
PA 2 ABBEY SQ, CHESTER, CH1 2HU, ENGLAND
SN 2053-230X
J9 ACTA CRYSTALLOGR F
JI Acta Crystallogr. F-Struct. Biol. Commun.
PD FEB
PY 2015
VL 71
BP 199
EP 205
DI 10.1107/S2053230X15000217
PN 2
PG 7
WC Biochemical Research Methods; Biochemistry & Molecular Biology;
Biophysics; Crystallography
SC Biochemistry & Molecular Biology; Biophysics; Crystallography
GA CB0YN
UT WOS:000349353700015
PM 25664796
ER
PT J
AU Kuzmina, Z
Gounden, V
Curtis, L
Avila, D
Taylor, T
Baruffaldi, J
Cowen, EW
Naik, HB
Hasni, SA
Mays, JW
Mitchell, S
Baird, K
Steinberg, SM
Pavletic, SZ
AF Kuzmina, Zoya
Gounden, Verena
Curtis, Lauren
Avila, Daniele
Taylor, Tiffani
Baruffaldi, Judy
Cowen, Edward W.
Naik, Haley B.
Hasni, Sarfaraz A.
Mays, Jacqueline W.
Mitchell, Sandra
Baird, Kristin
Steinberg, Seth M.
Pavletic, Steven Z.
TI Clinical significance of autoantibodies in a large cohort of patients
with chronic graft-versus-host disease defined by NIH criteria
SO AMERICAN JOURNAL OF HEMATOLOGY
LA English
DT Article
ID STEM-CELL TRANSPLANTATION; MINOR HISTOCOMPATIBILITY ANTIGEN; BONE-MARROW
TRANSPLANTATION; REFRACTORY CHRONIC GVHD; B-CELL; RITUXIMAB; SEVERITY;
BAFF; MULTICENTER; CORRELATE
AB There is an unmet need for identifying new clinical biomarkers in chronic Graft-versus-Host-disease (cGVHD) suitable for diagnosis and disease monitoring. Circulating autoantibodies represent an ongoing immune response and suggest a pathogenic role for B cells in cGVHD. Autoantibodies could be useful markers of cGVHD disease activity, severity, or organ specificity; however, their clinical utility is not established. The focus of this study was to determine the incidence and associations of a broad array of clinical autoantibodies with cGVHD manifestations in a large patient cohort characterized by NIH criteria. A panel of 21 circulating antibodies commonly used in clinical medicine was tested in 280 cGVHD patients (70% severe) enrolled in a cross-sectional prospective natural history study. Median cGVHD duration was two years. Patients with circulating autoantibodies (62%) had significantly higher levels of IgM (P<0.0001), IgG (P<0.0001), and IgA (P=0.001), elevated uric acid (P=0.008) and total protein (P=0.0004), and higher numbers of CD3+ (P=0.002), CD4+ (P=0.001), CD8+ (P=0.023) T cells, and CD19+ B cells (P<0.0001). Multiple antibodies were detected in 35% of patients. Prior rituximab therapy (n=66) was associated with reduced presence of autoantibodies (48 vs. 66% P=0.01). Only oral cGVHD was significantly associated with presence of autoantibodies in this study (P=0.028). No significant associations were found between cGVHD activity and severity, and presence of autoantibodies. Circulating autoantibodies are common in patients with advanced cGVHD. Their presence is associated with better quantitative immunologic reconstitution but does not have utility as a clinical biomarker of cGVHD. Am. J. Hematol. 90:114-119, 2015. (c) 2014 Wiley Periodicals, Inc.
C1 [Kuzmina, Zoya; Curtis, Lauren; Avila, Daniele; Taylor, Tiffani; Baruffaldi, Judy; Pavletic, Steven Z.] NCI, Graft Versus Host & Autoimmun Unit, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA.
[Kuzmina, Zoya] Evangel Hosp, Dept Internal Med, Vienna, Austria.
[Gounden, Verena] NCI, Dept Lab Med, Ctr Clin, NIH, Bethesda, MD 20892 USA.
[Cowen, Edward W.; Naik, Haley B.] NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA.
[Hasni, Sarfaraz A.] NIAMSD, NCI, NIH, Bethesda, MD USA.
[Mays, Jacqueline W.] Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA.
[Mitchell, Sandra] NIH, Outcomes Res Branch, Div Canc Control & Populat Sci, Bethesda, MD USA.
[Baird, Kristin] NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Steinberg, Seth M.] NIH, Biostat & Data Management Sect, Ctr Canc Res, Bethesda, MD USA.
RP Kuzmina, Z (reprint author), NCI, Graft Versus Host & Autoimmun Unit, Expt Transplantat & Immunol Branch, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM Zoya.Kuzmina@gmail.com
NR 46
TC 3
Z9 5
U1 0
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0361-8609
EI 1096-8652
J9 AM J HEMATOL
JI Am. J. Hematol.
PD FEB
PY 2015
VL 90
IS 2
BP 114
EP 119
DI 10.1002/ajh.23885
PG 6
WC Hematology
SC Hematology
GA CA4AL
UT WOS:000348846600011
PM 25363867
ER
PT J
AU Keppler-Noreuil, KM
Rios, JJ
Parker, VER
Semple, RK
Lindhurst, MJ
Sapp, JC
Alomari, A
Ezaki, M
Dobyns, W
Biesecker, LG
AF Keppler-Noreuil, Kim M.
Rios, Jonathan J.
Parker, Victoria E. R.
Semple, Robert K.
Lindhurst, Marjorie J.
Sapp, Julie C.
Alomari, Ahmad
Ezaki, Marybeth
Dobyns, William
Biesecker, Leslie G.
TI PIK3CA-Related Overgrowth Spectrum (PROS): Diagnostic and Testing
Eligibility Criteria, Differential Diagnosis, and Evaluation
SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A
LA English
DT Article
DE somatic mosaicism; PIK3CA gene; fibroadipose overgrowth; segmental
overgrowth; macrodactyly; CLOVES syndrome; PIK3CA-Related Overgrowth
Spectrum (PROS)
ID ACTIVATING MUTATIONS; PROTEUS-SYNDROME; CLOVES SYNDROME; MEGALENCEPHALY
SYNDROMES; EPIDERMAL-NEVI; PIK3CA CAUSE; GENE; MALFORMATIONS; AKT3
AB Somatic activating mutations in the phosphatidylinositol-3-kinase/AKT/mTOR pathway underlie heterogeneous segmental overgrowth phenotypes. Because of the extreme differences among patients, we sought to characterize the phenotypic spectrum associated with different genotypes and mutation burdens, including a better understanding of associated complications and natural history. Historically, the clinical diagnoses in patients with PIK3CA activating mutations have included Fibroadipose hyperplasia or Overgrowth (FAO), Hemihyperplasia Multiple Lipomatosis (HHML), Congenital Lipomatous Overgrowth, Vascular Malformations, Epidermal Nevi, Scoliosis/Skeletal and Spinal (CLOVES) syndrome, macrodactyly, Fibroadipose Infiltrating Lipomatosis, and the related megalencephaly syndromes, Megalencephaly-Capillary Malformation (MCAP or M-CM) and Dysplastic Megalencephaly (DMEG). A workshop was convened at the National Institutes of Health (NIH) to discuss and develop a consensus document regarding diagnosis and treatment of patients with PIK3CA-associated somatic overgrowth disorders. Participants in the workshop included a group of researchers from several institutions who have been studying these disorders and have published their findings, as well as representatives from patient-advocacy and support groups. The umbrella term of PIK3CA-Related Overgrowth Spectrum (PROS) was agreed upon to encompass both the known and emerging clinical entities associated with somatic PIK3CA mutations including, macrodactyly, FAO, HHML, CLOVES, and related megalencephaly conditions. Key clinical diagnostic features and criteria for testing were proposed, and testing approaches summarized. Preliminary recommendations for a uniform approach to assessment of overgrowth and molecular diagnostic testing were determined. Future areas to address include the surgical management of overgrowth tissue and vascular anomalies, the optimal approach to thrombosis risk, and the testing of potential pharmacologic therapies. (c) 2014 Wiley Periodicals, Inc.
C1 [Keppler-Noreuil, Kim M.; Lindhurst, Marjorie J.; Sapp, Julie C.; Biesecker, Leslie G.] NHGRI, NIH, Bethesda, MD 20892 USA.
[Rios, Jonathan J.] Univ Texas SW Med Ctr Dallas, Sarah M & Charles E Seay Ctr Musculoskeletal Res, Eugene McDermott Ctr Human Growth & Dev, Texas Scottish Rite Hosp Children,Dept Pediat, Dallas, TX 75390 USA.
[Rios, Jonathan J.; Ezaki, Marybeth] Univ Texas SW Med Ctr Dallas, Dept Orthopaed Surg, Dallas, TX 75390 USA.
[Parker, Victoria E. R.; Semple, Robert K.] Univ Cambridge, Metab Res Labs, Inst Metab Sci, Cambridge, MA USA.
[Alomari, Ahmad] Boston Childrens Hosp, Div Vasc & Intervent Radiol, Boston, MA USA.
[Alomari, Ahmad] Harvard Univ, Sch Med, Boston, MA USA.
[Dobyns, William] Univ Washington, Seattle, WA 98195 USA.
RP Keppler-Noreuil, KM (reprint author), NHGRI, NIH, 49 Convent,4A83, Bethesda, MD 20892 USA.
EM kim.keppler-noreuil@nih.gov
OI Semple, Robert/0000-0001-6539-3069; Dobyns, William/0000-0002-7681-2844
FU National Human Genome Research Institute; UK: Wellcome Trust, Clinical
Research Training Fellowship, UK national Institute for Health Research
(NIHR) Cambridge Biomedical Research Centre
FX Grant sponsors: National Human Genome Research Institute; UK: Wellcome
Trust, Clinical Research Training Fellowship, UK national Institute for
Health Research (NIHR) Cambridge Biomedical Research Centre.
NR 35
TC 35
Z9 35
U1 2
U2 7
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 FEB
PY 2015
VL 167
IS 2
BP 287
EP 295
DI 10.1002/ajmg.a.36836
PG 9
WC Genetics & Heredity
SC Genetics & Heredity
GA CA3ZJ
UT WOS:000348843600006
PM 25557259
ER
PT J
AU Kuhn, JH
Durrwald, R
Bao, YM
Briese, T
Carbone, K
Clawson, AN
deRisi, JL
Garten, W
Jahrling, PB
Kolodziejek, J
Rubbenstroth, D
Schwemmle, M
Stenglein, M
Tomonaga, K
Weissenbock, H
Nowotny, N
AF Kuhn, Jens H.
Duerrwald, Ralf
Bao, Yiming
Briese, Thomas
Carbone, Kathryn
Clawson, Anna N.
deRisi, Joseph L.
Garten, Wolfgang
Jahrling, Peter B.
Kolodziejek, Jolanta
Rubbenstroth, Dennis
Schwemmle, Martin
Stenglein, Mark
Tomonaga, Keizo
Weissenboeck, Herbert
Nowotny, Norbert
TI Taxonomic reorganization of the family Bornaviridae
SO ARCHIVES OF VIROLOGY
LA English
DT Article
ID BORNA-DISEASE-VIRUS; PROVENTRICULAR DILATATION DISEASE; STRAND RNA
VIRUS; AVIAN BORNAVIRUS; STANDARDIZED NOMENCLATURE; PSITTACINE BIRDS;
SPECIES LEVEL; IDENTIFICATION; VARIANTS; GENOTYPE
AB Knowledge of bornaviruses has expanded considerably during the last decade. A possible reservoir of mammalian Borna disease virus has been identified, divergent bornaviruses have been detected in birds and reptiles, and endogenous bornavirus-like elements have been discovered in the genomes of vertebrates of several species. Previous sequence comparisons and alignments have indicated that the members of the current family Bornaviridae are phylogenetically diverse and are not adequately classified in the existing bornavirus taxonomy supported by the International Committee on Taxonomy of Viruses (ICTV). We provide an update of these analyses and describe their implications for taxonomy. We propose retaining the family name Bornaviridae and the genus Bornavirus but reorganizing species classification. PAirwise Sequence Comparison (PASC) of bornavirus genomes and Basic Local Alignment Search Tool (BLAST) comparison of genomic and protein sequences, in combination with other already published phylogenetic analyses and known biological characteristics of bornaviruses, indicate that this genus should include at least five species: Mammalian 1 bornavirus (classical Borna disease virus and divergent Borna disease virus isolate No/98), Psittaciform 1 bornavirus (avian/psittacine bornaviruses 1, 2, 3, 4, 7), Passeriform 1 bornavirus (avian/canary bornaviruses C1, C2, C3, LS), Passeriform 2 bornavirus (estrildid finch bornavirus EF), and Waterbird 1 bornavirus (avian bornavirus 062(CG)). This classification is also in line with biological characteristics of these viruses and their vertebrate hosts. A snake bornavirus, proposed to be named Loveridge's garter snake virus 1, should be classified as a member of an additional species (Elapid 1 bornavirus), unassigned to a genus, in the family Bornaviridae. Avian bornaviruses 5, 6, MALL, and another "reptile bornavirus" ("Gaboon viper virus") should stay unclassified until further information becomes available. Finally, we propose new virus names and abbreviations when necessary to achieve clear differentiation and unique identification.
C1 [Kuhn, Jens H.; Clawson, Anna N.; Jahrling, Peter B.] NIAID, Integrated Res Facil Ft Detrick IRF Frederick, DCR, NIH, Ft Detrick, MD 20884 USA.
[Duerrwald, Ralf] IDT Biol GmbH, Dessau Rosslau, Germany.
[Bao, Yiming] NIH, Informat Engn Branch, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA.
[Briese, Thomas] Columbia Univ, Mailman Sch Publ Hlth, Ctr Infect & Immun, New York, NY USA.
[Carbone, Kathryn] NIH, Bethesda, MD 20892 USA.
[deRisi, Joseph L.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA.
[deRisi, Joseph L.] Univ Calif San Francisco, Dept Biochem & Biophys, San Francisco, CA 94143 USA.
[deRisi, Joseph L.] Univ Calif San Francisco, Dept Microbiol, San Francisco, CA 94143 USA.
[Garten, Wolfgang] Univ Marburg, Inst Virol, D-35032 Marburg, Germany.
[Kolodziejek, Jolanta; Nowotny, Norbert] Univ Vet Med Vienna, Dept Pathobiol, Viral Zoonoses Emerging & Vector Borne Infect Grp, Inst Virol, A-1210 Vienna, Austria.
[Rubbenstroth, Dennis; Schwemmle, Martin] Univ Med Ctr Freiburg, Inst Virol, Freiburg, Germany.
[Stenglein, Mark] Colorado State Univ, Dept Microbiol Immunol & Pathol, Ft Collins, CO 80523 USA.
[Tomonaga, Keizo] Kyoto Univ, Inst Virus Res, Kyoto 606, Japan.
[Weissenboeck, Herbert] Univ Vet Med Vienna, Dept Pathobiol, Inst Pathol & Forens Vet Med, A-1210 Vienna, Austria.
[Nowotny, Norbert] Sultan Qaboos Univ, Dept Microbiol & Immunol, Coll Med & Hlth Sci, Muscat, Oman.
RP Kuhn, JH (reprint author), NIAID, Integrated Res Facil Ft Detrick IRF Frederick, DCR, NIH, B-8200 Res Plaza, Ft Detrick, MD 20884 USA.
EM kuhnjens@mail.nih.gov; Norbert.Nowotny@vetmeduni.ac.at
RI Stenglein, Mark/E-3541-2017;
OI Stenglein, Mark/0000-0002-0993-813X; Kuhn, Jens H./0000-0002-7800-6045
FU National Institutes of Health/National Institute of Allergy and
Infectious Diseases [HHSN272200700016I]; National Institutes of Health,
National Library of Medicine
FX We would like to thank Laura Bollinger and Jiro Wada of the
IRF-Frederick for critically editing the manuscript and creating/editing
figures. JHK performed this work as an employee of Tunnell Government
Services, Inc., and ANC, as the owner of Logos Consulting, Inc., both
subcontractors to Battelle Memorial Institute under its prime contract
with the National Institutes of Health/National Institute of Allergy and
Infectious Diseases, under Contract No. HHSN272200700016I. This research
was also supported in part by the Intramural Research Program of the
National Institutes of Health, National Library of Medicine (YB).
NR 65
TC 22
Z9 23
U1 2
U2 25
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 FEB
PY 2015
VL 160
IS 2
BP 621
EP 632
DI 10.1007/s00705-014-2276-z
PG 12
WC Virology
SC Virology
GA CB2CE
UT WOS:000349433500042
PM 25449305
ER
PT J
AU Maslak, E
Zabielski, P
Kochan, K
Kus, K
Jasztal, A
Sitek, B
Proniewski, B
Wojcik, T
Gula, K
Kij, A
Walczak, M
Baranska, M
Chabowski, A
Holland, RJ
Saavedra, JE
Keefer, LK
Chlopicki, S
AF Maslak, Edyta
Zabielski, Piotr
Kochan, Kamila
Kus, Kamil
Jasztal, Agnieszka
Sitek, Barbara
Proniewski, Bartosz
Wojcik, Tomasz
Gula, Katarzyna
Kij, Agnieszka
Walczak, Maria
Baranska, Malgorzata
Chabowski, Adrian
Holland, Ryan J.
Saavedra, Joseph E.
Keefer, Larry K.
Chlopicki, Stefan
TI The liver-selective NO donor, V-PYRRO/NO, protects against liver
steatosis and improves postprandial glucose tolerance in mice fed high
fat diet
SO BIOCHEMICAL PHARMACOLOGY
LA English
DT Article
DE Nitric oxide; Hepatoprotection; Liver steatosis; Glucose tolerance;
Fatty acid metabolism
ID NITRIC-OXIDE SYNTHASE; NECROSIS-FACTOR-ALPHA; CONTROLLED-TRIAL; IN-VIVO;
NONALCOHOLIC STEATOHEPATITIS; MITOCHONDRIAL BIOGENESIS; HEPATIC
MICROCIRCULATION; INDUCED HEPATOTOXICITY; INSULIN-RESISTANCE; L-ARGININE
AB Background and purpose: There is an unmet medical need for novel NAFLD treatments. Here we have examined the effects of liver-selective NO donor (V-PYRRO/NO) as compared with metformin on hepatic steatosis and glucose tolerance in mice fed high fat diet.
Material and methods: Effects of V-PYRRO/NO (5 mg kg(-1)) or metformin (616 mg kg(-1)) were examined in C57BL/6J mice fed high fat diet (HF, 60 kcal% fat). Quantitative determination of steatosis, liver fatty acid composition and western blot analysis of selected proteins involved in mitochondrial biogenesis, fatty acid de nova synthesis and oxidation, triacylglycerols and cholesterol transport from the liver were performed. Liver NO and nitrate concentration and blood biochemistry were also analyzed.
Results: V-PYRRO/NO and metformin reduced liver steatosis with simultaneous reduction of total liver triacylglycerols, diacylglycerols and ceramides fraction and reversed HF-induced decrease in UFA/SFA ratio. V-PYRRO/NO substantially improved postprandial glucose tolerance, while the effect of metformin was modest and more pronounced on HOMA IR index. The anti-steatotic mechanism of V-PYRRO/NO was dependent on NO release, differed from that of metformin and involved improved glucose tolerance and inhibition of de novo fatty acid synthesis by Akt activation and ACC phosphorylation. In turn, major mechanism of metformin action involved increased expression of proteins implicated in mitochondrial biogenesis and metabolism (PGC-1 alpha, PPAR alpha, COX IV, cytochrome c, HADHSC).
Conclusions: V-PYRRO/NO acts as a liver-specific NO donor prodrug affording pronounced anti-steatotic effects and may represent an efficient, mechanistically novel approach to prevent liver steatosis and insulin resistance. (C) 2015 Elsevier Inc. All rights reserved.
C1 [Maslak, Edyta; Kochan, Kamila; Kus, Kamil; Jasztal, Agnieszka; Sitek, Barbara; Proniewski, Bartosz; Wojcik, Tomasz; Gula, Katarzyna; Kij, Agnieszka; Walczak, Maria; Baranska, Malgorzata; Chlopicki, Stefan] Jagiellonian Univ, Jagiellonian Ctr Expt Therapeut, PL-30348 Krakow, Poland.
[Chlopicki, Stefan] Jagiellonian Univ, Coll Med, Chair Pharmacol, Dept Expt Pharmacol, PL-31531 Krakow, Poland.
[Zabielski, Piotr; Chabowski, Adrian] Med Univ Bialystok, Dept Physiol, PL-15222 Bialystok, Poland.
[Kus, Kamil; Walczak, Maria] Jagiellonian Univ, Coll Med, Dept Pharmacokinet & Phys Pharm, PL-30688 Krakow, Poland.
[Kochan, Kamila; Baranska, Malgorzata] Jagiellonian Univ, Fac Chem, PL-30060 Krakow, Poland.
[Holland, Ryan J.; Keefer, Larry K.] NCI, Biol Chem Lab, Frederick, MD 21702 USA.
[Saavedra, Joseph E.] Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
RP Chlopicki, S (reprint author), Jagiellonian Univ, Jagiellonian Ctr Expt Therapeut, Bobrzynskiego 14, PL-30348 Krakow, Poland.
EM edyta.maslak@jcet.eu; piotrz@umb.edu.pl; kochan@chemia.uj.edu.pl;
kamil.kus@jcet.eu; agnieszka.jasztal@jcet.eu; barbara.sitek@jcet.eu;
bartosz.proniewski@jcet.eu; tomasz.wojcik@jcet.eu;
katarzyna.gula@jcet.eu; agnieszka.kij@jcet.eu; maria.walczak@jcet.eu;
baranska@chemia.uj.edu.pl; adrian@umb.edu.pl; hollandrj@mail.nih.gov;
saavedjo@mail.nih.gov; keeferl@mail.nih.gov; stefan.chlopicki@jcet.eu
RI Keefer, Larry/N-3247-2014
OI Keefer, Larry/0000-0001-7489-9555
FU European Union [POIG.01.01.02-00-069/09]; National Cancer Institute,
National Institutes of Health [HHSN26120080001E]; Intramural Research
Program of the NIH, National Cancer Institute, Center for Cancer
Research
FX This study was supported by European Union from the resources of the
European Regional Development Fund under the Innovative Economy
Programme (grant coordinated by JCET-UJ, No. POIG.01.01.02-00-069/09),
and partially by federal funds from the National Cancer Institute,
National Institutes of Health, under Contract HHSN26120080001E and by
the Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research.
NR 57
TC 4
Z9 4
U1 2
U2 13
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0006-2952
EI 1873-2968
J9 BIOCHEM PHARMACOL
JI Biochem. Pharmacol.
PD FEB 1
PY 2015
VL 93
IS 3
BP 389
EP 400
DI 10.1016/j.bcp.2014.12.004
PG 12
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA CB2AP
UT WOS:000349429400014
PM 25534988
ER
PT J
AU Leijnse, JNAL
Hallett, M
Sonneveld, GJ
AF Leijnse, J. N. A. L.
Hallett, M.
Sonneveld, G. J.
TI A multifactorial conceptual model of peripheral neuromusculoskeletal
predisposing factors in task-specific focal hand dystonia in musicians:
etiologic and therapeutic implications
SO BIOLOGICAL CYBERNETICS
LA English
DT Article
DE Hand; Biomechanics; Control; Focal dystonia; Overuse; Musicians
ID FLEXOR DIGITORUM PROFUNDUS; MEASURING FORCE TRANSFERS; MULTI-FINGER
TASKS; WRITERS CRAMP; ANATOMICAL RESTRICTIONS; TRIGGERING FACTORS;
OVERUSE SYNDROME; MOTOR CORTEX; DEEP FLEXORS; BRAIN
AB A model is presented showing how peripheral factors may cause a process of movement adaptation that leads to task-specific focal hand dystonia in musicians (FHDM). To acquire a playing technique, the hand must find effective and physiologically sustainable movements within a complex set of functional demands and anatomic, ergonomic, and physiological constraints. In doing so, individually discriminating constraints may become effective, such as limited anatomic independence of finger muscles/tendons, limited joint ranges of motion, or (subclinical) neuromusculoskeletal defects. These factors may, depending on the instrument-specific playing requirements, compromise or exclude functional playing movements. The controller (i.e., the brain) then needs to develop alternative motions to execute the task, which is called compensation. We hypothesize that, if this compensation process does not converge to physiologically sustainable muscle activation patterns that satisfy all constraints, compensation could increase indefinitely under the pressure of practice. Dystonic symptoms would become manifest when overcompensation occurs, resulting in motor patterns that fail in proper task execution. The model presented in this paper only concerns the compensatory processes preceding such overcompensations and does not aim to explain the nature of the dystonic motions themselves. While the model considers normal learning processes in the development of compensations, neurological predispositions could facilitate developing overcompensations or further abnormal motor programs. The model predicts that if peripheral factors are involved, FHDM symptoms would be preceded by long-term gradual changes in playing movements, which could be validated by prospective studies. Furthermore, the model implies that treatment success might be enhanced by addressing the conflict between peripheral factors and playing tasks before decompensating/retraining the affected movements.
C1 [Leijnse, J. N. A. L.] Univ Libre Bruxelles, Fac Sci Appl, Dept Bio Electro & Mech Syst BEAMS, B-1050 Brussels, Belgium.
[Leijnse, J. N. A. L.] Univ Libre Bruxelles, Erasme Univ Hosp, Dept Orthoped & Traumatol, B-1050 Brussels, Belgium.
[Hallett, M.] NINDS, Human Motor Control Sect, Med Neurol Branch, NIH, Bethesda, MD 20892 USA.
[Sonneveld, G. J.] Bethesda Hosp, Hoogeveen, Netherlands.
RP Leijnse, JNAL (reprint author), Univ Libre Bruxelles, Fac Sci Appl, Dept Bio Electro & Mech Syst BEAMS, Av Fr Roosevelt 50, B-1050 Brussels, Belgium.
EM jleijn@yahoo.com
FU Dystonia Medical Research Foundation, Chicago, IL; University of
Louisville (IRIG-MRG grant), Louisville, KY, USA; Universite Libre de
Bruxelles, Brussels, Belgium; NINDS Intramural Program
FX The authors thank J. E. Bonte, MD, J. C. Van der Meulen, MD, PhD, J. M.
F. Landsmeer, MD, PhD, C. W. Spoor, PhD, J. C. Snijders, PhD, A. B. M.
Rietveld, MD, A. Gupta, MD, N. Campbell-Kyureghyan, PhD, P. M. Quesada,
PhD, W. P. Hnat, PhD, G. Prater, PhD, P. Mathys, PhD, A. Delchambre,
PhD, and F. Schuind, MD, PhD, for their support. This paper is part of
the study 'Anatomical variations predisposing to focal dystonia in the
musicians' hand', supported by the Dystonia Medical Research Foundation,
Chicago, IL (http://www.dystonia-foundation.org), the University of
Louisville (IRIG-MRG grant), Louisville, KY, USA, and the Universite
Libre de Bruxelles, Brussels, Belgium. Dr. Hallett is supported by the
NINDS Intramural Program.
NR 83
TC 4
Z9 4
U1 1
U2 10
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0340-1200
EI 1432-0770
J9 BIOL CYBERN
JI Biol. Cybern.
PD FEB
PY 2015
VL 109
IS 1
BP 109
EP 123
DI 10.1007/s00422-014-0631-5
PG 15
WC Computer Science, Cybernetics; Neurosciences
SC Computer Science; Neurosciences & Neurology
GA CB1RN
UT WOS:000349405800008
PM 25323627
ER
PT J
AU Ali, SA
Steinberg, SM
Mossoba, M
Rimando, J
Rowley, S
Donato, ML
Camphausen, K
Sigal, G
Hakim, F
Gress, R
Halverson, D
Fowler, D
AF Ali, Syed Abbas
Steinberg, Seth M.
Mossoba, Miriam
Rimando, Joseph
Rowley, Scott
Donato, Michele L.
Camphausen, Kevin
Sigal, George
Hakim, Fran
Gress, Ronald
Halverson, David
Fowler, Daniel
TI Plasma IL-7 and IL-15 Levels Vary Greatly after Low-Intensity
Conditioning and May be Associated with Clinical Outcome in Recipients
of High-Dose Sirolimus GVHD Prophylaxis
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Meeting Abstract
CT BMT Tandem Meetings
CY FEB 11-15, 2015
CL San Diego, CA
C1 [Ali, Syed Abbas] NCI, Expt Transplant & Immunol Branch, NIH, Bethesda, MD 20892 USA.
[Steinberg, Seth M.] NCI, Biostat & Data Management Sect, Ctr Canc Res, NIH, Rockville, MD USA.
[Mossoba, Miriam] NCI, ETIB, Bethesda, MD 20892 USA.
[Rimando, Joseph] NIH, Med Res Scholars Program, Bethesda, MD 20892 USA.
[Rowley, Scott] Hackensack Univ, Med Ctr, John Theurer Canc Ctr, Hackensack, NJ USA.
[Camphausen, Kevin] NCI, Radiat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Sigal, George] Meso Scale Diagnost, Gaithersburg, MD USA.
[Hakim, Fran; Fowler, Daniel] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA.
[Gress, Ronald] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA.
[Halverson, David] NCI, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1083-8791
EI 1523-6536
J9 BIOL BLOOD MARROW TR
JI Biol. Blood Marrow Transplant.
PD FEB
PY 2015
VL 21
IS 2
SU 1
MA 378
BP S266
EP S267
PG 2
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA CA0UZ
UT WOS:000348633000380
ER
PT J
AU Anandi, P
Duhavin, N
Jain, NA
Chokshi, PD
Anand, A
Le, RQ
Ito, S
Barrett, AJ
Battiwalla, M
AF Anandi, Prathima
Duhavin, Neil
Jain, Natasha A.
Chokshi, Puja D.
Anand, Ankit
Le, Robert Q.
Ito, Sawa
Barrett, A. John
Battiwalla, Minoo
TI Blood Stream Infection Is Frequent during Conditioning but Does Not
Impact Allogeneic Transplant Outcomes in the Modern Era
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Meeting Abstract
CT BMT Tandem Meetings
CY FEB 11-15, 2015
CL San Diego, CA
C1 [Anandi, Prathima; Duhavin, Neil; Jain, Natasha A.; Chokshi, Puja D.; Anand, Ankit; Le, Robert Q.; Ito, Sawa; Barrett, A. John; Battiwalla, Minoo] NHLBI, Hematol Branch, 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 1083-8791
EI 1523-6536
J9 BIOL BLOOD MARROW TR
JI Biol. Blood Marrow Transplant.
PD FEB
PY 2015
VL 21
IS 2
SU 1
MA 380
BP S268
EP S268
PG 1
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA CA0UZ
UT WOS:000348633000382
ER
PT J
AU Anandi, P
Jain, NA
Wu, C
Tian, X
Pophali, PA
Koklanaris, E
Dunavin, N
Ito, S
Le, RQ
Savani, BN
Barrett, AJ
Battiwalla, M
AF Anandi, Prathima
Jain, Natasha A.
Wu, Colin
Tian, Xin
Pophali, Priyanka A.
Koklanaris, Eleftheria
Dunavin, Neil
Ito, Sawa
Le, Robert Q.
Savani, Bipin N.
Barrett, A. John
Battiwalla, Minoo
TI Bone Mineral Density (BMD) Improves in Survivors in Their Second Decade
Post-Allogeneic Stem Cell Transplantation and Is Influenced By Body Mass
Index (BMI) and Age
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Meeting Abstract
CT BMT Tandem Meetings
CY FEB 11-15, 2015
CL San Diego, CA
C1 [Anandi, Prathima; Jain, Natasha A.; Pophali, Priyanka A.; Koklanaris, Eleftheria; Dunavin, Neil; Ito, Sawa; Le, Robert Q.; Barrett, A. John; Battiwalla, Minoo] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
[Wu, Colin; Tian, Xin] NHLBI, Off Biostat Res, NIH, Bethesda, MD 20892 USA.
[Savani, Bipin N.] Vanderbilt Univ, Med Ctr, Nashville, TN USA.
RI Pophali, Priyanka/P-8646-2016
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 1083-8791
EI 1523-6536
J9 BIOL BLOOD MARROW TR
JI Biol. Blood Marrow Transplant.
PD FEB
PY 2015
VL 21
IS 2
SU 1
MA 213
BP S171
EP S171
PG 1
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA CA0UZ
UT WOS:000348633000218
ER
PT J
AU Buxbaum, NP
Farthing, DE
Boehrer, AC
Kapoor, V
Castro, E
Bouladoux, NJ
Swan, G
Telford, W
Eckhaus, M
Belkaid, Y
Bosselut, R
Gress, R
AF Buxbaum, Nataliya Prokopenko
Farthing, Donald Eugene
Boehrer, Andrea Carpenter
Kapoor, Veena
Castro, Ehydel
Bouladoux, Nicolas Jean
Swan, Gregory
Telford, William
Eckhaus, Michael
Belkaid, Yasmine
Bosselut, Remy
Gress, Ronald
TI T Regulatory Cell Kinetics Are Altered in a Target Organ of Chronic
GVHD, Resulting in a Low T Regulatory to T Effector Memory Cell Ratio
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Meeting Abstract
CT BMT Tandem Meetings
CY FEB 11-15, 2015
CL San Diego, CA
C1 [Buxbaum, Nataliya Prokopenko; Farthing, Donald Eugene; Kapoor, Veena; Telford, William] NCI, ETIB, NIH, Bethesda, MD 20892 USA.
[Boehrer, Andrea Carpenter; Bosselut, Remy] NCI, Lab Immune Cell Biol, NIH, Bethesda, MD 20892 USA.
[Castro, Ehydel; Swan, Gregory] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA.
[Bouladoux, Nicolas Jean; Belkaid, Yasmine] NIAID, Mucosal Immunol Sect, NIH, Bethesda, MD 20892 USA.
[Eckhaus, Michael] NCI, Diagnost & Res Serv Branch, NIH, Bethesda, MD 20892 USA.
[Gress, Ronald] NCI, Co Senior Expt Transplantat & Immunol Branch, 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 1083-8791
EI 1523-6536
J9 BIOL BLOOD MARROW TR
JI Biol. Blood Marrow Transplant.
PD FEB
PY 2015
VL 21
IS 2
SU 1
MA 474
BP S327
EP S328
PG 2
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA CA0UZ
UT WOS:000348633000476
ER
PT J
AU Chakrabarty, JH
Nguyen, CT
Havlicek, JP
Vesely, SK
Lindenberg, L
Adler, S
Blacklock-Schuver, BAJ
Kurdziel, K
Lin, F
Avila, D
Selby, GB
Mann, J
Hsu, J
Chai, A
Epstein, RB
Duong, NQT
Li, SB
Krauss, T
Hopps, S
Pham, T
Bollard, CM
Choyke, P
Gress, R
Williams, KM
AF Chakrabarty, Jennifer Holter
Nguyen, Chuong T.
Havlicek, Joseph P.
Vesely, Sara K.
Lindenberg, Liza
Adler, Steve
Blacklock-Schuver, Bazetta A. J.
Kurdziel, Karen
Lin, Frank
Avila, Daniele
Selby, George B.
Mann, Jennifer
Hsu, Jennifer
Chai, Amy
Epstein, Robert B.
Duong, Ngoc Quyen T.
Li, Shibo
Krauss, Teresa
Hopps, Sarah
Pham, Tom
Bollard, Catherine M.
Choyke, Peter
Gress, Ronald
Williams, Kirsten M.
TI Novel Imaging Analysis of the Marrow Compartment after Myeloablative
HSCT Reveals the Kinetics and Degree of Myeloablation and Cell Recovery
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Meeting Abstract
CT BMT Tandem Meetings
CY FEB 11-15, 2015
CL San Diego, CA
C1 [Chakrabarty, Jennifer Holter] Univ Oklahoma, Peggy & Charles Stephenson Canc Ctr, Oklahoma City, OK USA.
[Nguyen, Chuong T.] Univ Oklahoma, Co First Sch Elect & Comp Engn, Norman, OK 73019 USA.
[Havlicek, Joseph P.] Univ Oklahoma, Sch Elect & Comp Engn, Norman, OK 73019 USA.
[Vesely, Sara K.] Univ Oklahoma, Hlth Sci Ctr, Stephenson Canc Ctr, Oklahoma City, OK USA.
[Lindenberg, Liza; Adler, Steve; Kurdziel, Karen; Choyke, Peter] NIH, Mol Imaging Branch, Bethesda, MD 20892 USA.
[Blacklock-Schuver, Bazetta A. J.; Avila, Daniele; Mann, Jennifer; Hsu, Jennifer; Chai, Amy] NCI, ETIB, NIH, Bethesda, MD 20892 USA.
[Lin, Frank] NCI, Canc Imaging Program, NIH, Bethesda, MD 20892 USA.
[Selby, George B.; Epstein, Robert B.; Duong, Ngoc Quyen T.; Li, Shibo; Krauss, Teresa; Pham, Tom] Univ Oklahoma, Hlth Sci Ctr, Stephenson Canc Ctr, Oklahoma City, OK USA.
[Hopps, Sarah] Univ Oklahoma, Oklahoma City, OK USA.
[Bollard, Catherine M.] Childrens Natl Med Ctr, Ctr Canc & Immunol Res, Washington, DC 20010 USA.
[Gress, Ronald] NCI, Co Senior Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA.
[Williams, Kirsten M.] NCI, CNMC, 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 1083-8791
EI 1523-6536
J9 BIOL BLOOD MARROW TR
JI Biol. Blood Marrow Transplant.
PD FEB
PY 2015
VL 21
IS 2
SU 1
MA 462
BP S319
EP S320
PG 2
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA CA0UZ
UT WOS:000348633000464
ER
PT J
AU Chang, K
Merideth, M
Stratton, P
AF Chang, Katherine
Merideth, Melissa
Stratton, Pamela
TI Women's Health and Hormonal Treatment Options for Therapeutic Amenorrhea
and Contraception during the Peri-Transplant Period
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Meeting Abstract
CT BMT Tandem Meetings
CY FEB 11-15, 2015
CL San Diego, CA
C1 [Chang, Katherine] Northwestern, Obstet & Gynecol, Chicago, IL USA.
[Merideth, Melissa] Natl Human Genome Inst, Bethesda, MD USA.
[Stratton, Pamela] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1083-8791
EI 1523-6536
J9 BIOL BLOOD MARROW TR
JI Biol. Blood Marrow Transplant.
PD FEB
PY 2015
VL 21
IS 2
SU 1
MA 236
BP S183
EP S183
PG 1
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA CA0UZ
UT WOS:000348633000240
ER
PT J
AU Chokshi, PD
Anandi, P
Jain, NA
Dunavin, N
Le, RQ
Ito, S
Barrett, AJ
Battiwalla, M
AF Chokshi, Puja D.
Anandi, Prathima
Jain, Natasha A.
Dunavin, Neil
Le, Robert Q.
Ito, Sawa
Barrett, A. John
Battiwalla, Minoo
TI Minor ABO Incompatibility Does Not Impact Non-Relapse Mortality in
T-Cell Depleted HLA-Matched Sibling Transplantation
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Meeting Abstract
CT BMT Tandem Meetings
CY FEB 11-15, 2015
CL San Diego, CA
C1 [Chokshi, Puja D.; Anandi, Prathima; Jain, Natasha A.; Dunavin, Neil; Le, Robert Q.; Ito, Sawa; Barrett, A. John; Battiwalla, Minoo] NHLBI, Hematol Branch, 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 1083-8791
EI 1523-6536
J9 BIOL BLOOD MARROW TR
JI Biol. Blood Marrow Transplant.
PD FEB
PY 2015
VL 21
IS 2
SU 1
MA 391
BP S276
EP S277
PG 2
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA CA0UZ
UT WOS:000348633000393
ER
PT J
AU Curtis, LM
Cantilena, C
Yau, YY
Chinn, T
Hsu, J
Pirsl, F
Baruffaldi, JL
Hakim, F
Fowler, D
Gress, R
Pavletic, SZ
AF Curtis, Lauren M.
Cantilena, Cathy
Yau, Yu Ying
Chinn, Tracey
Hsu, Jennifer
Pirsl, Filip
Baruffaldi, Judy L.
Hakim, Fran
Fowler, Daniel
Gress, Ronald
Pavletic, Steven Z.
TI Leukapheresis Safely and Effectively Yields Lymphocyte Populations
Sufficient for Chronic Gvhd Research
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Meeting Abstract
CT BMT Tandem Meetings
CY FEB 11-15, 2015
CL San Diego, CA
C1 [Curtis, Lauren M.] NCI, Med Oncol Serv, NIH, Bethesda, MD 20892 USA.
[Curtis, Lauren M.; Chinn, Tracey; Hsu, Jennifer; Pirsl, Filip; Baruffaldi, Judy L.; Hakim, Fran; Fowler, Daniel; Pavletic, Steven Z.] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA.
[Cantilena, Cathy; Yau, Yu Ying] NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA.
[Gress, Ronald] NCI, Co Senior Expt Transplantat & Immunol Branch, 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 1083-8791
EI 1523-6536
J9 BIOL BLOOD MARROW TR
JI Biol. Blood Marrow Transplant.
PD FEB
PY 2015
VL 21
IS 2
SU 1
MA 476
BP S328
EP S329
PG 2
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA CA0UZ
UT WOS:000348633000478
ER
PT J
AU Curtis, LM
Datiles, MB
Steinberg, SM
Bishop, RJ
Cowen, EW
Mays, J
Pirsl, F
Baruffaldi, JL
Hsu, J
Mitchell, SA
Pavletic, SZ
AF Curtis, Lauren M.
Datiles, Manuel B., III
Steinberg, Seth M.
Bishop, Rachel J.
Cowen, Edward W.
Mays, Jacqueline
Pirsl, Filip
Baruffaldi, Judy L.
Hsu, Jennifer
Mitchell, Sandra A.
Pavletic, Steven Z.
TI Predictive Models Using NIH Criteria and Clinical Characteristics Define
Diagnosis, Disease Activity and Risk Factors for Chronic Ocular
Graft-Versus Host Disease
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Meeting Abstract
CT BMT Tandem Meetings
CY FEB 11-15, 2015
CL San Diego, CA
C1 [Curtis, Lauren M.; Pirsl, Filip; Baruffaldi, Judy L.; Pavletic, Steven Z.] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA.
[Datiles, Manuel B., III; Bishop, Rachel J.] NEI, NIH, Bethesda, MD 20892 USA.
[Steinberg, Seth M.] NCI, Biostat & Data Management Sect, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Cowen, Edward W.] NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA.
[Mays, Jacqueline] Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA.
[Hsu, Jennifer] NCI, ETIB, NIH, Bethesda, MD 20892 USA.
[Mitchell, Sandra A.] NCI, Outcomes Res Branch, Div Canc Control & Populat Sci, NIH, Rockville, MD 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 1083-8791
EI 1523-6536
J9 BIOL BLOOD MARROW TR
JI Biol. Blood Marrow Transplant.
PD FEB
PY 2015
VL 21
IS 2
SU 1
MA 475
BP S328
EP S328
PG 1
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA CA0UZ
UT WOS:000348633000477
ER
PT J
AU Halverson, D
Mossoba, M
Hansen, B
Schuver, BB
Steinberg, SM
Hakim, F
Ali, SA
Kurlander, R
Gea-Banacloche, J
Hickstein, D
Pavletic, SZ
Khuu, H
Stroncek, DF
Bishop, MR
Gress, R
Fowler, D
AF Halverson, David
Mossoba, Miriam
Hansen, Brenna
Schuver, Bazetta Blacklock
Steinberg, Seth M.
Hakim, Fran
Ali, Syed Abbas
Kurlander, Roger
Gea-Banacloche, Juan
Hickstein, Dennis
Pavletic, Steven Z.
Khuu, Hanh
Stroncek, David F.
Bishop, Michael R.
Gress, Ronald
Fowler, Daniel
TI Pilot Clinical Trial of Lymphocyte-Selective Pentostatin Plus
Cyclophosphamide Conditioning, High Dose Sirolimus and Pre-Emptive DLI
with Rapamycin-Resistant Donor CD4+T Cells
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Meeting Abstract
CT BMT Tandem Meetings
CY FEB 11-15, 2015
CL San Diego, CA
C1 [Halverson, David; Hansen, Brenna; Schuver, Bazetta Blacklock; Gea-Banacloche, Juan; Hickstein, Dennis] NCI, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA.
[Mossoba, Miriam] NCI, ETIB, Bethesda, MD 20892 USA.
[Steinberg, Seth M.] NCI, Biostat & Data Management Sect, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Hakim, Fran; Pavletic, Steven Z.; Fowler, Daniel] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA.
[Ali, Syed Abbas] NCI, Expt Transplantat & Immunol Branch, NIH, Little Rock, AR USA.
[Kurlander, Roger] NIH, Ctr Clin, Bethesda, MD 20892 USA.
[Khuu, Hanh] NIH, Dept Transfus Med, Bethesda, MD 20892 USA.
[Stroncek, David F.] NIH, Dept Transfus Med, Bethesda, MD 20892 USA.
[Bishop, Michael R.] Univ Chicago, Chicago, IL 60637 USA.
[Gress, Ronald] NCI, Expt Transplantat & Immunol Branch, 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 1083-8791
EI 1523-6536
J9 BIOL BLOOD MARROW TR
JI Biol. Blood Marrow Transplant.
PD FEB
PY 2015
VL 21
IS 2
SU 1
MA 409
BP S286
EP S288
PG 3
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA CA0UZ
UT WOS:000348633000411
ER
PT J
AU Hanley, PJ
Melenhorst, J
Nikiforow, S
Scheinberg, P
Cruz, R
Krance, RA
Leung, K
Martinez, C
Heslop, HE
Rooney, CM
Barrett, AJ
Shpall, EJ
Bollard, CM
AF Hanley, Patrick J.
Melenhorst, Jan
Nikiforow, Sarah
Scheinberg, Phillip
Cruz, Russell
Krance, Robert A.
Leung, Kathryn
Martinez, Caridad
Heslop, Helen E.
Rooney, Cliona M.
Barrett, A. John
Shpall, Elizabeth J.
Bollard, Catherine M.
TI CMVpp65-Specific T Cells Generated from Naive T Cell Populations
Recognize Atypical but Not Canonical Epitopes and May Be Protective In
Vivo
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Meeting Abstract
CT BMT Tandem Meetings
CY FEB 11-15, 2015
CL San Diego, CA
C1 [Hanley, Patrick J.] Childrens Natl Med Ctr, CETI, Washington, DC 20010 USA.
[Melenhorst, Jan] NHLBI, NIH, Bethesda, MD 20892 USA.
[Nikiforow, Sarah] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
[Scheinberg, Phillip] Hosp Beneficencia Portuguesa Sao Paulo, Antonio Ermirio de Moraes Oncol Ctr, Sao Paulo, Brazil.
[Cruz, Russell] Childrens Natl Med Ctr, Sheikh Zayad Inst, Washington, DC 20010 USA.
[Krance, Robert A.] Houston Methodist Hosp, Baylor Coll Med, Ctr Cell & Gene Therapy, Houston, TX USA.
[Krance, Robert A.] Texas Childrens Hosp, Houston, TX 77030 USA.
[Leung, Kathryn; Martinez, Caridad] Texas Childrens Hosp, Baylor Coll Med, Ctr Cell & Gene Therapy, Houston, TX 77030 USA.
[Heslop, Helen E.; Rooney, Cliona M.] Houston Methodist Hosp, Texas Childrens Hosp, Baylor Coll Med, Ctr Cell & Gene Therapy, Houston, TX USA.
[Barrett, A. John] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Bollard, Catherine M.] Childrens Natl Med Ctr, Ctr Canc & Immunol Res, Washington, DC 20010 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 1083-8791
EI 1523-6536
J9 BIOL BLOOD MARROW TR
JI Biol. Blood Marrow Transplant.
PD FEB
PY 2015
VL 21
IS 2
SU 1
MA 33
BP S51
EP S52
PG 2
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA CA0UZ
UT WOS:000348633000038
ER
PT J
AU Heimall, J
Logan, BR
Cowan, MJ
Notarangelo, LD
Griffith, LM
Puck, J
Parikh, S
O'Reilly, RJ
Pai, SY
Hanson, IC
Martinez, C
Pulsipher, MA
Kapoor, N
Goldman, F
Kletzel, M
Filipovich, L
Cuvellier, G
Thakar, M
Burroughs, L
Knudsen, A
Connelly, JA
Quigg, TC
Smith, AR
Sullivan, K
Loechelt, BJ
Gillio, AP
Haddad, E
Kohn, DB
Fleisher, T
Shearer, W
Dvorak, CC
Buckley, RH
AF Heimall, Jennifer
Logan, Brent R.
Cowan, Morton J.
Notarangelo, Luigi D.
Griffith, Linda M.
Puck, Jennifer
Parikh, Suhag
O'Reilly, Richard J.
Pai, Sung-Yun
Hanson, Imelda C.
Martinez, Caridad
Pulsipher, Michael A.
Kapoor, Neena
Goldman, Frederick
Kletzel, Morris
Filipovich, Lisa
Cuvellier, Geoff
Thakar, Monica
Burroughs, Lauri
Knudsen, Alan
Connelly, James A.
Quigg, Troy C.
Smith, Angela R.
Sullivan, Kathleen
Loechelt, Brett J.
Gillio, Alfred P.
Haddad, Elie
Kohn, Donald B.
Fleisher, Thomas
Shearer, William
Dvorak, Christopher C.
Buckley, Rebecca H.
TI Early Hematopoietic Cell Transplant (HCT) Outcomes of Children with
Severe Combined Immunodeficiency Disease (SCID): The First Seventy Four
Patients of the Primary Immune Deficiency Treatment Consortium (PIDTC)
Prospective Study 6901
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Meeting Abstract
CT BMT Tandem Meetings
CY FEB 11-15, 2015
CL San Diego, CA
C1 [Heimall, Jennifer] Childrens Hosp Philadelphia, Div Allergy & Immunol, Philadelphia, PA 19104 USA.
[Logan, Brent R.] Med Coll Wisconsin, Div Biostat, Milwaukee, WI 53226 USA.
[Cowan, Morton J.; Puck, Jennifer] UCSF Benioff Childrens Hosp, Pediat Allergy Immunol & Blood & Marrow Transplan, San Francisco, CA USA.
[Notarangelo, Luigi D.] Harvard Univ, Sch Med, Childrens Hosp Boston, Program Primary Immunodeficiencies, Boston, MA USA.
[Griffith, Linda M.] NIAID, DAIT, NIH, Bethesda, MD 20892 USA.
[Parikh, Suhag] Duke Univ, Med Ctr, Pediat BMT Program, Durham, NC USA.
[O'Reilly, Richard J.] Mem Sloan Kettering Canc Ctr, New York, NY USA.
[Pai, Sung-Yun] Boston Childrens Hosp, Boston, MA USA.
[Hanson, Imelda C.; Shearer, William] Texas Childrens Hosp, Baylor Coll Med, Houston, TX 77030 USA.
[Martinez, Caridad] Texas Childrens Hosp, Baylor Coll Med, Ctr Cell & Gene Therapy, Houston, TX 77030 USA.
[Pulsipher, Michael A.] Univ Utah, Sch Med, Huntsman Canc Inst, Salt Lake City, UT USA.
[Kapoor, Neena] Childrens Hosp Los Angeles, Div Hematol Oncol & Blood & Marrow Transplantat, Los Angeles, CA 90027 USA.
[Goldman, Frederick] Univ Alabama Birmingham, Dept Pediat, Birmingham, AL USA.
[Kletzel, Morris] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA.
[Filipovich, Lisa] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA.
[Cuvellier, Geoff] CC Manitoba, Winnipeg, MB, Canada.
[Thakar, Monica] Med Coll Wisconsin, Milwaukee, WI 53226 USA.
[Burroughs, Lauri] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Knudsen, Alan] St Louis Univ, St Louis, MO 63103 USA.
[Connelly, James A.] Univ Michigan, Pediat Blood & Marrow Transplant Program, Ann Arbor, MI 48109 USA.
[Quigg, Troy C.] Texas Transplant Inst, San Antonio, TX USA.
[Smith, Angela R.] Univ Minnesota, Med Ctr, Minneapolis, MN 55455 USA.
[Sullivan, Kathleen] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
[Loechelt, Brett J.] Childrens Natl Med Ctr, Washington, DC 20010 USA.
[Gillio, Alfred P.] Hackensack Univ, Med Ctr, Inst Pediat Canc & Blood Disorders, Hackensack, NJ USA.
[Haddad, Elie] Ste Justine Hosp, Montreal, PQ, Canada.
[Kohn, Donald B.] Univ Calif Los Angeles, Div Hematol Oncol, Mattel Childrens Hosp, Los Angeles, CA USA.
[Fleisher, Thomas] NIH, Lab Host Def, Bethesda, MD 20892 USA.
[Dvorak, Christopher C.] Univ San Francisco, San Francisco, CA 94117 USA.
[Buckley, Rebecca H.] Duke Univ, Med Ctr, Durham, NC USA.
RI Notarangelo, Luigi/F-9718-2016
OI Notarangelo, Luigi/0000-0002-8335-0262
NR 0
TC 1
Z9 1
U1 1
U2 4
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 FEB
PY 2015
VL 21
IS 2
SU 1
MA 413
BP S289
EP S291
PG 3
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA CA0UZ
UT WOS:000348633000415
ER
PT J
AU Jain, NA
Chen, MY
Shanbhag, S
Anandi, P
Lu, K
Pophali, PA
Dunavin, N
Ito, S
Koklanaris, E
Hourigan, CS
Barrett, AJ
Battiwalla, M
AF Jain, Natasha A.
Chen, Marcus Y.
Shanbhag, Sujata
Anandi, Prathima
Lu, Kit
Pophali, Priyanka A.
Dunavin, Neil
Ito, Sawa
Koklanaris, Eleftheria
Hourigan, Christopher S.
Barrett, A. John
Battiwalla, Minoo
TI Cardiac CT Imaging Is a Feasible Screening Strategy for Coronary Artery
Disease (CAD) in Long Term Allogeneic Stem Cell Transplant (Allo-SCT)
Survivors
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Meeting Abstract
CT BMT Tandem Meetings
CY FEB 11-15, 2015
CL San Diego, CA
C1 [Jain, Natasha A.; Anandi, Prathima; Lu, Kit; Pophali, Priyanka A.; Dunavin, Neil; Ito, Sawa; Koklanaris, Eleftheria; Hourigan, Christopher S.; Barrett, A. John; Battiwalla, Minoo] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
[Chen, Marcus Y.; Shanbhag, Sujata] NHLBI, Cardiol Branch, NIH, Bethesda, MD 20892 USA.
RI Pophali, Priyanka/P-8646-2016
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1083-8791
EI 1523-6536
J9 BIOL BLOOD MARROW TR
JI Biol. Blood Marrow Transplant.
PD FEB
PY 2015
VL 21
IS 2
SU 1
MA 60
BP S73
EP S73
PG 1
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA CA0UZ
UT WOS:000348633000065
ER
PT J
AU Kekre, N
Mak, K
Stopsack, K
Ishii, K
Binder, M
Branvall, E
Cutler, CS
AF Kekre, Natasha
Mak, Kimberley
Stopsack, Konrad
Ishii, Kazusa
Binder, Moritz
Branvall, Elsa
Cutler, Corey S.
TI Impact of HLA-Mismatch in Unrelated Donor Hematopoietic Stem Cell
Transplantation: A Comprehensive Meta-Analysis
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Meeting Abstract
CT BMT Tandem Meetings
CY FEB 11-15, 2015
CL San Diego, CA
C1 [Kekre, Natasha; Cutler, Corey S.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Mak, Kimberley] Harvard Radiat Oncol Program, Boston, MA USA.
[Stopsack, Konrad; Binder, Moritz] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
[Ishii, Kazusa] NIH, Bethesda, MD 20892 USA.
[Branvall, Elsa] Karolinska Univ Hosp, Stockholm, Sweden.
RI Binder, Moritz/D-3279-2016
OI Binder, Moritz/0000-0001-9014-9658
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1083-8791
EI 1523-6536
J9 BIOL BLOOD MARROW TR
JI Biol. Blood Marrow Transplant.
PD FEB
PY 2015
VL 21
IS 2
SU 1
MA 52
BP S66
EP S67
PG 2
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA CA0UZ
UT WOS:000348633000057
ER
PT J
AU Kohn, DB
Shaw, KL
Sokolic, R
Carbonaro, DA
Davila, A
Barman, P
Garabedian, E
Silvin, C
De Oliveira, S
Shah, AJ
Moore, TB
Hershfield, M
Thrasher, A
Gaspar, HR
Candotti, F
AF Kohn, Donald B.
Shaw, Kit L.
Sokolic, Robert
Carbonaro, Denise A.
Davila, Alejandar
Barman, Provaboti
Garabedian, Elizabeth
Silvin, Christopher
De Oliveira, Satiro
Shah, Ami J.
Moore, Theodore B.
Hershfield, Michael
Thrasher, Adrian
Gaspar, H. Robert
Candotti, Fabio
TI Autologous Transplant/Gene Therapy for Adenosine Deaminase-Deficient
Severe Combined Immune Deficiency
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Meeting Abstract
CT BMT Tandem Meetings
CY FEB 11-15, 2015
CL San Diego, CA
C1 [Kohn, Donald B.; Shaw, Kit L.; Carbonaro, Denise A.; Davila, Alejandar; Barman, Provaboti; Shah, Ami J.] Univ Calif Los Angeles, Los Angeles, CA USA.
[Sokolic, Robert] NHGRI, Bethesda, MD 20892 USA.
[Garabedian, Elizabeth; Silvin, Christopher] Natl Genome Res Inst, NIH, Bethesda, MD USA.
[De Oliveira, Satiro; Moore, Theodore B.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
[Hershfield, Michael] Duke Univ, Sch Med, Durham, NC USA.
[Thrasher, Adrian; Gaspar, H. Robert] UCL, Inst Child Hlth, London, England.
[Candotti, Fabio] NHGRI, NIH, Bethesda, MD 20892 USA.
RI De Oliveira, Satiro/D-8860-2014
OI De Oliveira, Satiro/0000-0002-8181-7316
NR 0
TC 0
Z9 0
U1 1
U2 7
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 FEB
PY 2015
VL 21
IS 2
SU 1
MA 100
BP S102
EP S102
PG 1
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA CA0UZ
UT WOS:000348633000105
ER
PT J
AU Palmer, J
Chai, XY
Martin, PJ
Pidala, J
Lazaryan, A
Arora, M
Cutler, CS
Pavletic, SZ
Pusic, I
Jagasia, MH
Inamoto, Y
Flowers, MED
Vogelsang, G
Lee, SJ
AF Palmer, Jeanne
Chai, Xiaoyu
Martin, Paul J.
Pidala, Joseph
Lazaryan, Aleksandr
Arora, Mukta
Cutler, Corey S.
Pavletic, Steven Z.
Pusic, Iskra
Jagasia, Madan H.
Inamoto, Yoshihiro
Flowers, Mary E. D.
Vogelsang, Georgia
Lee, Stephanie J.
TI Physician-Reported CR+PR at 6 Months Predicts Subsequent Survival in
Patients with Chronic GVHD
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Meeting Abstract
CT BMT Tandem Meetings
CY FEB 11-15, 2015
CL San Diego, CA
C1 [Palmer, Jeanne] Mayo Clin, Div Hematol Oncol, Phoenix, AZ USA.
[Chai, Xiaoyu; Martin, Paul J.; Flowers, Mary E. D.; Lee, Stephanie J.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA.
[Pidala, Joseph] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA.
[Lazaryan, Aleksandr; Arora, Mukta] Univ Minnesota, Med Ctr, Minneapolis, MN 55455 USA.
[Cutler, Corey S.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
[Pavletic, Steven Z.] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA.
[Pusic, Iskra] Washington Univ, Med Ctr, St Louis, MO USA.
[Jagasia, Madan H.] Vanderbilt Univ, Med Ctr, Dept Med, Div Hematol Oncol, Nashville, TN USA.
[Inamoto, Yoshihiro] Natl Canc Ctr, Stem Cell Transplantat Div, Tokyo, Japan.
[Vogelsang, Georgia] Johns Hopkins Med Ctr, Lutherville Timonium, MD 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 1083-8791
EI 1523-6536
J9 BIOL BLOOD MARROW TR
JI Biol. Blood Marrow Transplant.
PD FEB
PY 2015
VL 21
IS 2
SU 1
MA 43
BP S59
EP S60
PG 2
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA CA0UZ
UT WOS:000348633000048
ER
PT J
AU Pirsl, F
Curtis, LM
Steinberg, SM
Katic, M
Dobbin, M
Hsu, J
Avila, D
Taylor, T
Baruffaldi, JL
Barsony, J
Pavletic, SZ
AF Pirsl, Filip
Curtis, Lauren M.
Steinberg, Seth M.
Katic, Masenjka
Dobbin, Marnie
Hsu, Jennifer
Avila, Daniele
Taylor, Tiffani
Baruffaldi, Judy L.
Barsony, Julianna
Pavletic, Steven Z.
TI High Incidence of Osteoporosis in a Natural History Cohort of Patients
with Moderate to Severe Chronic Graft-Versus-Host Disease and Risk
Factor Analysis
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Meeting Abstract
CT BMT Tandem Meetings
CY FEB 11-15, 2015
CL San Diego, CA
C1 [Pirsl, Filip; Curtis, Lauren M.; Katic, Masenjka; Taylor, Tiffani; Baruffaldi, Judy L.; Pavletic, Steven Z.] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA.
[Curtis, Lauren M.] NCI, Med Oncol Serv, NIH, Bethesda, MD 20892 USA.
[Steinberg, Seth M.] NCI, Biostat & Data Management Sect, NIH, Bethesda, MD 20892 USA.
[Dobbin, Marnie] NIH, Dept Clin Nutr, Ctr Clin, Bethesda, MD 20892 USA.
[Hsu, Jennifer; Avila, Daniele] NCI, ETIB, NIH, Bethesda, MD 20892 USA.
[Barsony, Julianna] Georgetown Univ, Div Endocrinol & Metab, Washington, DC 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 1083-8791
EI 1523-6536
J9 BIOL BLOOD MARROW TR
JI Biol. Blood Marrow Transplant.
PD FEB
PY 2015
VL 21
IS 2
SU 1
MA 67
BP S77
EP S77
PG 1
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA CA0UZ
UT WOS:000348633000072
ER
PT J
AU Pulsipher, MA
Logan, BR
Kiefer, DM
Chitphakdithai, P
Switzer, GE
Riches, ML
Rizzo, JD
Anderlini, P
Leitman, SF
Varni, JW
Kobusingye, H
Besser, RM
Miller, JP
Drexler, RJ
King, RJ
Horowitz, MM
Confer, DL
AF Pulsipher, Michael A.
Logan, Brent R.
Kiefer, Deidre M.
Chitphakdithai, Pintip
Switzer, Galen E.
Riches, Marcie L.
Rizzo, J. Douglas
Anderlini, Paolo
Leitman, Susan F.
Varni, James W.
Kobusingye, Hati
Besser, RaeAnne M.
Miller, John P.
Drexler, Rebecca J.
King, Roberta J.
Horowitz, Mary M.
Confer, Dennis L.
TI Related PBSC Donors Experience Higher Levels of Pain and
Donation-Related Symptoms and Less Complete Rates of Recovery Compared
to Unrelated Donors: Primary Analysis of the Related Donor Safety Study
(RDSafe)
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Meeting Abstract
CT BMT Tandem Meetings
CY FEB 11-15, 2015
CL San Diego, CA
C1 [Pulsipher, Michael A.] Univ Utah, Sch Med, Huntsman Canc Inst, Salt Lake City, UT USA.
[Logan, Brent R.] Med Coll Wisconsin, Div Biostat, Milwaukee, WI 53226 USA.
[Logan, Brent R.; Rizzo, J. Douglas; Horowitz, Mary M.] Med Coll Wisconsin, CIBMTR, Milwaukee, WI 53226 USA.
[Kiefer, Deidre M.; Chitphakdithai, Pintip; Kobusingye, Hati; Besser, RaeAnne M.; Drexler, Rebecca J.; Confer, Dennis L.] Ctr Int Blood & Marrow Transplant Res, Natl Marrow Donor Program, Minneapolis, MN USA.
[Switzer, Galen E.] Univ Pittsburgh, Pittsburgh, PA USA.
[Riches, Marcie L.] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA.
[Anderlini, Paolo] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Leitman, Susan F.] NHLBI, Dept Transfus Med, NIH, Bethesda, MD 20892 USA.
[Varni, James W.] Texas A&M Univ, College Stn, TX USA.
[Miller, John P.] Dept Donor Med Serv, Natl Marrow Donor Program, Minneapolis, MN USA.
[King, Roberta J.] CIBMTR, Natl Marrow Donor Program, Minneapolis, MN 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 1083-8791
EI 1523-6536
J9 BIOL BLOOD MARROW TR
JI Biol. Blood Marrow Transplant.
PD FEB
PY 2015
VL 21
IS 2
SU 1
MA 20
BP S41
EP S42
PG 2
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA CA0UZ
UT WOS:000348633000025
ER
PT J
AU Pulsipher, MA
Logan, BR
Kiefer, DM
Chitphakdithai, P
Pedersen, TL
Stroncek, DF
Williams, EP
O'Donnell, PV
Majhail, NS
Confer, DL
Shaw, BE
AF Pulsipher, Michael A.
Logan, Brent R.
Kiefer, Deidre M.
Chitphakdithai, Pintip
Pedersen, Tanya L.
Stroncek, David F.
Williams, Eric P.
O'Donnell, Paul V.
Majhail, Navneet S.
Confer, Dennis L.
Shaw, Bronwen E.
TI The Effect of Race, Socioeconomic Status, and Collection Center Size on
Bone Marrow (BM) and Peripheral Blood Stem Cell (PBSC) Donor Experiences
at National Marrow Donor Program (NMDP) Collection Centers
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Meeting Abstract
CT BMT Tandem Meetings
CY FEB 11-15, 2015
CL San Diego, CA
C1 [Pulsipher, Michael A.] Univ Utah, Sch Med, Huntsman Canc Inst, Salt Lake City, UT USA.
[Logan, Brent R.] Med Coll Wisconsin, Div Biostat, Milwaukee, WI 53226 USA.
[Logan, Brent R.; Shaw, Bronwen E.] Med Coll Wisconsin, CIBMTR, Milwaukee, WI 53226 USA.
[Kiefer, Deidre M.] Ctr Int Blood & Marrow Transplant Res, Natl Marrow Donor Program, Minneapolis, MN USA.
[Chitphakdithai, Pintip; Confer, Dennis L.] CIBMTR, Natl Marrow Donor Program, Minneapolis, MN USA.
[Pedersen, Tanya L.] Allina Hlth, Minneapolis, MN USA.
[Stroncek, David F.] NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA.
[Williams, Eric P.] Natl Marrow Donor Program, Dept Bioinformat Res, Minneapolis, MN USA.
[O'Donnell, Paul V.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA.
[Majhail, Navneet S.] Cleveland Clin, Blood & Marrow Transplant Program, Cleveland, OH 44106 USA.
NR 0
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 1083-8791
EI 1523-6536
J9 BIOL BLOOD MARROW TR
JI Biol. Blood Marrow Transplant.
PD FEB
PY 2015
VL 21
IS 2
SU 1
MA 19
BP S40
EP S41
PG 2
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA CA0UZ
UT WOS:000348633000024
ER
PT J
AU Purev, E
Gormley, N
Ramos, C
Reger, R
Tian, X
Cho, E
Reda, D
Chen, C
Suffredini, AF
Childs, RW
AF Purev, Enkhtsetseg
Gormley, Nicole
Ramos, Catalina
Reger, Robert
Tian, Xin
Cho, Elena
Reda, Debra
Chen, Clara
Suffredini, Anthony F.
Childs, Richard W.
TI Inhaled Cyclosporine Solution for the Treatment of Bronchiolitis
Obliterans Following Hematopoietic Stem Cell Transplantation (HSCT) or
Lung Transplantation
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Meeting Abstract
CT BMT Tandem Meetings
CY FEB 11-15, 2015
CL San Diego, CA
C1 [Purev, Enkhtsetseg; Gormley, Nicole; Ramos, Catalina; Reger, Robert; Cho, Elena; Childs, Richard W.] NHLBI, Hematol Branch, Bethesda, MD 20892 USA.
[Tian, Xin] NHLBI, Off Biostat Res, NIH, Bethesda, MD 20892 USA.
[Reda, Debra; Suffredini, Anthony F.] NIH, Dept Crit Care Med, Bethesda, MD 20892 USA.
[Chen, Clara] NIH, Dept Radiol & Imaging Sci, 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 1083-8791
EI 1523-6536
J9 BIOL BLOOD MARROW TR
JI Biol. Blood Marrow Transplant.
PD FEB
PY 2015
VL 21
IS 2
SU 1
MA 505
BP S347
EP S348
PG 2
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA CA0UZ
UT WOS:000348633000506
ER
PT J
AU Ritzau, N
Aker, D
AF Ritzau, Nicole
Aker, Diane
TI Eliminating Cross Contamination from Intravenous Cyclosporine and
Tacrolimus and Accurate Blood Sampling
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Meeting Abstract
CT BMT Tandem Meetings
CY FEB 11-15, 2015
CL San Diego, CA
C1 [Ritzau, Nicole; Aker, Diane] NIH, Ctr Clin, 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 1083-8791
EI 1523-6536
J9 BIOL BLOOD MARROW TR
JI Biol. Blood Marrow Transplant.
PD FEB
PY 2015
VL 21
IS 2
SU 1
MA 442
BP S306
EP S306
PG 1
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA CA0UZ
UT WOS:000348633000444
ER
PT J
AU Scrivani, C
Merideth, M
Pulanic, TK
Pavletic, SZ
Childs, RW
Hsieh, M
Stratton, P
AF Scrivani, Claire
Merideth, Melissa
Pulanic, Tajana Klepac
Pavletic, Steven Z.
Childs, Richard W.
Hsieh, Matthew
Stratton, Pamela
TI Early Diagnosis of Labial Fusion Enables Medical Treatment in an Office
Setting
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Meeting Abstract
CT BMT Tandem Meetings
CY FEB 11-15, 2015
CL San Diego, CA
C1 [Scrivani, Claire] NHLBI, NIH, Bethesda, MD 20892 USA.
[Merideth, Melissa] Natl Human Genome Inst, Bethesda, MD USA.
[Pulanic, Tajana Klepac] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, Bethesda, MD USA.
[Pavletic, Steven Z.] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA.
[Childs, Richard W.] NHLBI, Hematol Branch, Bethesda, MD 20892 USA.
[Hsieh, Matthew] NIH, Bethesda, MD 20892 USA.
[Stratton, Pamela] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1083-8791
EI 1523-6536
J9 BIOL BLOOD MARROW TR
JI Biol. Blood Marrow Transplant.
PD FEB
PY 2015
VL 21
IS 2
SU 1
MA 237
BP S184
EP S184
PG 1
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA CA0UZ
UT WOS:000348633000241
ER
PT J
AU Shah, NN
Yates, B
Delbrook, C
Lee, DW
Fleisher, T
Rampertaap, S
Lemberg, K
Sabatino, M
Stroncek, DE
Zhang, H
Fry, TJ
Mackall, CL
AF Shah, Nirali N.
Yates, Bonnie
Delbrook, Cindy
Lee, Daniel W.
Fleisher, Thomas
Rampertaap, Shakuntala
Lemberg, Kimberly
Sabatino, Marianna
Stroncek, David E.
Zhang, Hua
Fry, Terry J.
Mackall, Crystal L.
TI Ex Vivo T Cell Depleted HLA-Matched PBSCT with Post-Transplant Activated
Donor-Derived NK Cell Infusions for High-Risk Acute Lymphoblastic
Leukemia
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Meeting Abstract
CT BMT Tandem Meetings
CY FEB 11-15, 2015
CL San Diego, CA
C1 [Shah, Nirali N.; Yates, Bonnie; Delbrook, Cindy; Lee, Daniel W.; Zhang, Hua; Fry, Terry J.; Mackall, Crystal L.] NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Fleisher, Thomas; Rampertaap, Shakuntala; Lemberg, Kimberly] NCI, Dept Lab Med, NIH, Bethesda, MD 20892 USA.
[Sabatino, Marianna; Stroncek, David E.] NIH, Dept Transfus Med, 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 1083-8791
EI 1523-6536
J9 BIOL BLOOD MARROW TR
JI Biol. Blood Marrow Transplant.
PD FEB
PY 2015
VL 21
IS 2
SU 1
MA 446
BP S309
EP S309
PG 1
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA CA0UZ
UT WOS:000348633000448
ER
PT J
AU Hinkle, SN
Laughon, SK
Catov, JM
Olsen, J
Bech, BH
AF Hinkle, S. N.
Laughon, S. K.
Catov, J. M.
Olsen, J.
Bech, B. H.
TI First trimester coffee and tea intake and risk of gestational diabetes
mellitus: a study within a national birth cohort
SO BJOG-AN INTERNATIONAL JOURNAL OF OBSTETRICS AND GYNAECOLOGY
LA English
DT Article
DE Caffeine; coffee; gestational diabetes; pregnancy; tea
ID UTERINE ARTERY DOPPLER; INTRAUTERINE GROWTH RESTRICTION; EARLY-ONSET
PREECLAMPSIA; ANGIOGENIC FACTORS; NULLIPAROUS WOMEN; 1ST-TRIMESTER
PREDICTION; PRETERM PREECLAMPSIA; BIOCHEMICAL MARKERS; EARLY-PREGNANCY;
PREVENTION
AB Objective Coffee and tea consumption is associated with a decreased type 2 diabetes risk in non-pregnant adults. We examined the relation between first trimester coffee and tea consumption and gestational diabetes mellitus (GDM) risk.
Design Population-based cohort study.
Setting Denmark 1996-2002.
Population Non-diabetic women with singleton pregnancies in the Danish National Birth Cohort (n = 71 239).
Methods Estimated adjusted relative risks (RR) and 95% confidence intervals (95% CI) for the association between first trimester coffee and tea or estimated total caffeine and GDM.
Main outcome measures GDM ascertained from the National Hospital Discharge Register or maternal interview.
Results Coffee or tea intake was reported in 81.2% (n = 57 882) and 1.3% (n = 912) of pregnancies were complicated by GDM. Among non-consumers, 1.5% of pregnancies were complicated by GDM. Among coffee drinkers, GDM was highest among women who drank = 8 cups/day (1.8%) with no significant difference across intake levels (P = 0.10). Among tea drinkers, there was no difference in GDM across intake levels (1.2%; P = 0.98). After adjustment for age, socio-occupational status, parity, pre-pregnancy body mass index, smoking, and cola, there was suggestion of a protective, but non-significant association with increasing coffee (RR = 8 versus 0 cups/day = 0.89 [95% CI 0.64-1.25]) and tea (RR = 8 versus 0 cups/day = 0.77 [95% CI 0.55-1.08]). Results were similar by smoking status, except a non-significant 1.45-fold increased risk with = 8 coffee cups/day for non-smokers. There was a non-significant reduced GDM risk with increasing total caffeine.
Conclusions Our results suggest that moderate first trimester coffee and tea intake were not associated with GDM increased risk and possibly may have a protective effect.
C1 [Hinkle, S. N.; Laughon, S. K.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Intramural Populat Hlth Res, NIH, Bethesda, MD 20892 USA.
[Catov, J. M.] Univ Pittsburgh, Dept Obstet, Pittsburgh, PA USA.
[Catov, J. M.] Univ Pittsburgh, Dept Gynecol, Pittsburgh, PA USA.
[Catov, J. M.] Univ Pittsburgh, Dept Reprod Serv, Pittsburgh, PA USA.
[Catov, J. M.] Univ Pittsburgh, Magee Womens Res Inst, Pittsburgh, PA USA.
[Olsen, J.; Bech, B. H.] Aarhus Univ, Inst Publ Hlth, Dept Epidemiol, Aarhus, Denmark.
RP Laughon, SK (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, NIH, 6100 Execut Blvd Room 7B03, Bethesda, MD 20892 USA.
EM laughonsk@mail.nih.gov
RI Olsen, Jorn/F-8801-2015; Hinkle, Stefanie/F-8253-2013; Bech, Bodil
Hammer/B-9646-2016;
OI Olsen, Jorn/0000-0001-7462-5140; Hinkle, Stefanie/0000-0003-4312-708X;
Grantz, Katherine/0000-0003-0276-8534
FU Danish National Research Foundation; Pharmacy Foundation; Egmont
Foundation; March of Dimes Birth Defects Foundation; Augustinus
Foundation; Intramural Research Program of the Eunice Kennedy Shriver
National Institute of Child Health and Human Development
FX The Danish National Research Foundation has established the Danish
Epidemiology Science Centre that initiated and created the Danish
National Birth Cohort. The cohort is furthermore a result of a major
grant from this Foundation. Additional support for the Danish National
Birth Cohort is provided by the Pharmacy Foundation, the Egmont
Foundation, the March of Dimes Birth Defects Foundation and the
Augustinus Foundation. This research was supported in part by the
Intramural Research Program of the Eunice Kennedy Shriver National
Institute of Child Health and Human Development.
NR 40
TC 4
Z9 4
U1 2
U2 38
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1470-0328
EI 1471-0528
J9 BJOG-INT J OBSTET GY
JI BJOG
PD FEB
PY 2015
VL 122
IS 3
BP 420
EP 428
DI 10.1111/1471-0528.12930
PG 9
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA CA4HZ
UT WOS:000348866600033
PM 24947484
ER
PT J
AU Jain, NA
Ito, S
Tian, X
Kurlander, R
Battiwalla, M
Lu, K
Savani, BN
Malkovska, V
Rezvani, K
Le, Q
Shenoy, A
Hourigan, CS
Keyvanfar, K
Koklanaris, E
Superata, J
Muranski, P
Barrett, AJ
Yong, ASM
AF Jain, N. A.
Ito, S.
Tian, X.
Kurlander, R.
Battiwalla, M.
Lu, K.
Savani, B. N.
Malkovska, V.
Rezvani, K.
Le, Q.
Shenoy, A.
Hourigan, C. S.
Keyvanfar, K.
Koklanaris, E.
Superata, J.
Muranski, P.
Barrett, A. J.
Yong, A. S. M.
TI Clinical and biological predictors of outcome following relapse of CML
post-allo-SCT
SO BONE MARROW TRANSPLANTATION
LA English
DT Article
ID CHRONIC MYELOID-LEUKEMIA; STEM-CELL TRANSPLANTATION; CHRONIC MYELOGENOUS
LEUKEMIA; GRAFT-VERSUS-LEUKEMIA; BONE-MARROW-TRANSPLANTATION; RESIDUAL
DISEASE DETECTION; POLYMERASE-CHAIN-REACTION; BCR-ABL TRANSCRIPTS;
MOLECULAR REMISSION; ALLOGENEIC TRANSPLANTATION
AB Although there are now fewer allo-SCTs performed for CML, leukemic relapse post transplant remains a persistent problem. To better define clinical and biological parameters determining postrelapse outcome, we studied 59 patients with CML relapsing after HLA-identical sibling allo-SCT between 1993 and 2008. Eighteen (30.5%) were transplanted in advanced phase and 41 (69.5%) in chronic phase. With a median follow-up from relapse of 7.9 years, 5-year post relapse survival (PRS) was 62%. Multivariate analysis found disease status at transplant, time to diagnosis of relapse from transplant and pretransplant tyrosine kinase inhibitor (TKI) use as significant factors associated with PRS. Analysis of BCR-ABL transcript expression in the hematopoietic progenitor compartment was performed in 36 patients (22 relapsed, 8 non-relapsed and 6 TKI alone controls). Patients with BCR-ABL expression in their early hematopoietic stem cell compartment (Lineage CD34(+)CD38 CD90(+)) had worse survival irrespective of the disease status. We conclude that disease status remains the strongest clinical prognostic factor for PRS in CML following allo-SCT. The persistence of BCR-ABL expression in the progenitor cell compartment in some patients after SCT emphasizes the need to target CML-leukemia stem cells.
C1 [Jain, N. A.; Ito, S.; Battiwalla, M.; Lu, K.; Savani, B. N.; Rezvani, K.; Le, Q.; Shenoy, A.; Hourigan, C. S.; Keyvanfar, K.; Koklanaris, E.; Superata, J.; Muranski, P.; Barrett, A. J.; Yong, A. S. M.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
[Tian, X.] NHLBI, Off Biostat Res, NIH, Bethesda, MD 20892 USA.
[Kurlander, R.] NIH, Dept Lab Med, Clin Res Ctr, Bethesda, MD 20892 USA.
[Malkovska, V.] Medstar Washington Hosp Ctr, Washington Canc Inst, Washington, DC USA.
RP Ito, S (reprint author), NHLBI, Hematol Branch, NIH, 10 Ctr Dr 10 CRC 5-3581, Bethesda, MD 20892 USA.
EM itos2@nhlbi.nih.gov
RI Hourigan, Christopher/S-2476-2016
OI Hourigan, Christopher/0000-0002-6189-8067
FU Intramural Research Program of the National Institutes of Health at the
National Heart, Lung, and Blood Institute
FX This paper is dedicated to the memory of John Michael Goldman who
inspired us with his insightful observations on the definition and
nature of cure of CML. We thank N Hensel, S Miner, M Franco Colon and F
Chinian (Hematology Branch, NHLBI, NIH, USA) for their technical
support. We also thank all patients who participated in this study. This
research was supported by the Intramural Research Program of the
National Institutes of Health at the National Heart, Lung, and Blood
Institute.
NR 37
TC 1
Z9 1
U1 0
U2 0
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 FEB
PY 2015
VL 50
IS 2
BP 189
EP 196
DI 10.1038/bmt.2014.249
PG 8
WC Biophysics; Oncology; Hematology; Immunology; Transplantation
SC Biophysics; Oncology; Hematology; Immunology; Transplantation
GA CB1QM
UT WOS:000349402900006
PM 25387087
ER
PT J
AU Roberto, A
Castagna, L
Gandolfi, S
Zanon, V
Bramanti, S
Sarina, B
Crocchiolo, R
Todisco, E
Carlo-Stella, C
Tentorio, P
Timofeeva, I
Santoro, A
Della Bella, S
Roederer, M
Mavilio, D
Lugli, E
AF Roberto, A.
Castagna, L.
Gandolfi, S.
Zanon, V.
Bramanti, S.
Sarina, B.
Crocchiolo, R.
Todisco, E.
Carlo-Stella, C.
Tentorio, P.
Timofeeva, I.
Santoro, A.
Della Bella, S.
Roederer, M.
Mavilio, D.
Lugli, E.
TI B-cell reconstitution recapitulates B-cell lymphopoiesis following
haploidentical BM transplantation and post-transplant CY
SO BONE MARROW TRANSPLANTATION
LA English
DT Letter
ID IDENTIFICATION
C1 [Roberto, A.; Zanon, V.; Tentorio, P.; Della Bella, S.; Mavilio, D.; Lugli, E.] Humanitas Clin & Res Ctr, Unit Clin & Expt Immunol, Rozzano, Italy.
[Castagna, L.; Gandolfi, S.; Bramanti, S.; Sarina, B.; Crocchiolo, R.; Todisco, E.; Carlo-Stella, C.; Timofeeva, I.; Santoro, A.] Humanitas Clin & Res Ctr, Humanitas Canc Ctr, Hematol & Bone Marrow Transplant Unit, Rozzano, Italy.
[Della Bella, S.; Mavilio, D.] Univ Milan, Dept Med Biotechnol & Translat Med BioMeTra, Milan, Italy.
[Roederer, M.] NIAID, Vaccine Res Ctr, ImmunoTechnol Sect, NIH, Bethesda, MD 20892 USA.
RP Roberto, A (reprint author), Humanitas Clin & Res Ctr, Unit Clin & Expt Immunol, Rozzano, Italy.
EM domenico.mavilio@humanitas.it; enrico.lugli@humanitasresearch.it
OI Mavilio, Domenico/0000-0001-6147-0952; Castagna,
Luca/0000-0002-6239-7387; Della Bella, Silvia/0000-0003-0818-5049;
Roberto, Alessandra/0000-0001-6615-0026; Carlo-Stella,
Carmelo/0000-0003-3144-0124
FU Intramural NIH HHS
NR 9
TC 1
Z9 1
U1 0
U2 2
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0268-3369
EI 1476-5365
J9 BONE MARROW TRANSPL
JI Bone Marrow Transplant.
PD FEB
PY 2015
VL 50
IS 2
BP 317
EP 319
DI 10.1038/bmt.2014.266
PG 3
WC Biophysics; Oncology; Hematology; Immunology; Transplantation
SC Biophysics; Oncology; Hematology; Immunology; Transplantation
GA CB1QM
UT WOS:000349402900031
PM 25419693
ER
PT J
AU Cid, J
Lozano, M
Ziman, A
West, KA
O'Brien, KL
Murphy, MF
Wendel, S
Vazquez, A
Ortin, X
Hervig, TA
Delaney, M
Flegel, WA
Yazer, MH
AF Cid, Joan
Lozano, Miguel
Ziman, Alyssa
West, Kamille A.
O'Brien, Kerry L.
Murphy, Michael F.
Wendel, Silvano
Vazquez, Alejandro
Ortin, Xavier
Hervig, Tor A.
Delaney, Meghan
Flegel, Willy A.
Yazer, Mark H.
CA Biomedical Excellence Safer
TI Low frequency of anti-D alloimmunization following D plus platelet
transfusion: the Anti-D Alloimmunization after D-incompatible Platelet
Transfusions (ADAPT) study
SO BRITISH JOURNAL OF HAEMATOLOGY
LA English
DT Article
DE platelet transfusion; D compatibility; anti-D alloantibodies;
alloimmunization; RhIG
ID RED-BLOOD-CELLS; D-GAMMA-GLOBULIN; TRANSPLANT RECIPIENTS; HEMATOLOGIC
DISEASES; ONCOLOGY PATIENTS; RHD IMMUNIZATION; ABSENCE; DONORS;
ALLOANTIBODIES; PREVENTION
AB The reported frequency of D alloimmunization in D- recipients after transfusion of D+ platelets varies. This study was designed to determine the frequency of D alloimmunization, previously reported to be an average of 5 +/- 2%. A primary anti-D immune response was defined as the detection of anti-D28d following the first D+ platelet transfusion. Data were collected on 485 D- recipients of D+ platelets in 11 centres between 2010 and 2012. Their median age was 60 (range 2-100) years. Diagnoses included: haematological (203/485, 42%), oncological (64/485, 13%) and other diseases (218/485, 45%). Only 7/485 (144%; 95% CI 058-297%) recipients had a primary anti-D response after a median serological follow-up of 77d (range: 28-2111). There were no statistically significant differences between the primary anti-D formers and the other patients, in terms of gender, age, receipt of immunosuppressive therapy, proportion of patients with haematological/oncological diseases, transfusion of whole blood-derived or apheresis platelets or both, and total number of transfused platelet products. This is the largest study with the longest follow-up of D alloimmunization following D+ platelet transfusion. The low frequency of D alloimmunization should be considered when deciding whether to administer Rh Immune Globulin to D- males and D- females without childbearing potential after transfusion of D+ platelets.
C1 [Cid, Joan; Lozano, Miguel] UB, Hosp Clin, Dept Haemotherapy & Haemostasis, IDIBAPS, Barcelona, Spain.
[Cid, Joan; West, Kamille A.; Flegel, Willy A.] NIH, Ctr Clin, Dept Transfus Med, Bethesda, MD 20892 USA.
[Ziman, Alyssa] Univ Calif Los Angeles, David Geffen Sch Med, UCLA Div Transfus Med, Los Angeles, CA 90095 USA.
[O'Brien, Kerry L.] Beth Israel Deaconess Med Ctr, Dept Pathol, Boston, MA 02215 USA.
[Murphy, Michael F.] Oxford Univ Hosp & NHS Blood & Transplant, Oxford, England.
[Wendel, Silvano] Hosp Sirio Libanes Blood Bank, Sao Paulo, Brazil.
[Vazquez, Alejandro] Hosp Univ Puerta de Hierro, Dept Blood Transfus, Majadahonda, Spain.
[Ortin, Xavier] Hosp Verge de la Cinta, Dept Haematol, Tortosa, Spain.
[Hervig, Tor A.] Univ Bergen, Dept Clin Sci, Haukeland Univ Hosp, Bergen, Norway.
[Delaney, Meghan] Univ Washington, Dept Lab Med, Puget Sound Blood Ctr, Seattle, WA 98195 USA.
[Yazer, Mark H.] Univ Pittsburgh, Dept Pathol, Inst Transfus Med, Pittsburgh, PA USA.
RP Cid, J (reprint author), Hosp Clin Barcelona, Serv Hemoterapia & Hemostasia, C Villarroel 170, E-08036 Barcelona, Spain.
EM jcid@clinic.ub.es
RI Cid, Joan/F-7778-2016
OI Cid, Joan/0000-0001-5445-4508
FU Sociedad Espanola de Transfusion Sanguinea y Terapia Celular; NIH
Clinical Center
FX The authors would like to thank: Gloria Carbasse, from Department of
Haemotherapy and Haemostasis, Hospital Clinic, Barcelona, SPAIN; Kulvara
Anuruckparadorn, from UCLA Division of Transfusion Medicine, David
Geffen School of Medicine at UCLA, Los Angeles, CA; Sherry L Sheldon,
from Department of Transfusion Medicine, Clinical Center, National
Institutes of Health, Bethesda, MD; Julie Staves, from Oxford University
Hospitals and NHS Blood & Transplant, Oxford, UK; Arlete Lazar, from
Hospital Sirio Libanes Blood Bank, Sao Paulo, Brazil; Jose L. Bueno,
from Hospital Universitario Puerta de Hierro, Majadahonda, Spain; Jorunn
Vadheim, Department of Immunology and Transfusion Medicine, Haukeland
University Hospital, Norway; Megan Keane, from Department of Pathology,
University of Pittsburgh and the Institute for Transfusion Medicine,
Pittsburgh, PA. This research was supported in part by a sabbatical
leave and a research grant from the 'Sociedad Espanola de Transfusion
Sanguinea y Terapia Celular' for Joan Cid and by the Intramural Research
Program of the NIH Clinical Center.
NR 38
TC 9
Z9 9
U1 1
U2 4
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 FEB
PY 2015
VL 168
IS 4
BP 598
EP 603
DI 10.1111/bjh.13158
PG 6
WC Hematology
SC Hematology
GA CA8GZ
UT WOS:000349157200019
PM 25283094
ER
PT J
AU Zablotska, LB
Nadyrov, EA
Rozhko, AV
Gong, Z
Polyanskaya, ON
McConnell, RJ
O'Kane, P
Brenner, AV
Little, MP
Ostroumova, E
Bouville, A
Drozdovitch, V
Minenko, V
Demidchik, Y
Nerovnya, A
Yauseyenka, V
Savasteeva, I
Nikonovich, S
Mabuchi, K
Hatch, M
AF Zablotska, Lydia B.
Nadyrov, Eldar A.
Rozhko, Alexander V.
Gong, Zhihong
Polyanskaya, Olga N.
McConnell, Robert J.
O'Kane, Patrick
Brenner, Alina V.
Little, Mark P.
Ostroumova, Evgenia
Bouville, Andre
Drozdovitch, Vladimir
Minenko, Viktor
Demidchik, Yuri
Nerovnya, Alexander
Yauseyenka, Vassilina
Savasteeva, Irina
Nikonovich, Sergey
Mabuchi, Kiyohiko
Hatch, Maureen
TI Analysis of Thyroid Malignant Pathologic Findings Identified During 3
Rounds of Screening (1997-2008) of a Cohort of Children and Adolescents
from Belarus Exposed to Radioiodines After the Chernobyl Accident
SO CANCER
LA English
DT Article
DE thyroid cancer; pathology; morphology; thyroid neoplasms; Chernobyl
nuclear accident; papillary carcinoma; radiation; latency
ID CANCER RISK; RADIATION; CHILDHOOD; CARCINOMA; DISEASES; UKRAINE; I-131
AB BACKGROUND: Recent studies of children and adolescents who were exposed to radioactive iodine-131 (I-131) after the 1986 Chernobyl nuclear accident in Ukraine exhibited a significant dose-related increase in the risk of thyroid cancer, but the association of radiation doses with tumor histologic and morphologic features is not clear. METHODS: A cohort of 11,664 individuals in Belarus who were aged <= 18 years at the time of the accident underwent 3 cycles of thyroid screening during 1997 to 2008. I-131 thyroid doses were estimated from individual thyroid activity measurements taken within 2 months after the accident and from dosimetric questionnaire data. Demographic, clinical, and tumor pathologic characteristics of the patients with thyroid cancer were analyzed using 1-way analysis of variance, chi-square tests or Fisher exact tests, and logistic regression. RESULTS: In total, 158 thyroid cancers were identified as a result of screening. The majority of patients had T1a and T1b tumors (93.7%), with many positive regional lymph nodes (N1; 60.6%) but few distant metastases (M1; <1%). Higher I-131 doses were associated with higher frequency of solid and diffuse sclerosing variants of thyroid cancer (P<.01) and histologic features of cancer aggressiveness, such as lymphatic vessel invasion, intrathyroidal infiltration, and multifocality (all P<.03). Latency was not correlated with radiation dose. Fifty-two patients with self-reported thyroid cancers which were diagnosed before 1997 were younger at the time of the accident and had a higher percentage of solid variant cancers compared with patients who had screening-detected thyroid cancers (all P<.0001). CONCLUSIONS: I-131 thyroid radiation doses were associated with a significantly greater frequency of solid and diffuse sclerosing variants of thyroid cancer and various features of tumor aggressiveness. (C) 2014 American Cancer Society.
C1 [Zablotska, Lydia B.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
[Nadyrov, Eldar A.; Rozhko, Alexander V.; Polyanskaya, Olga N.; Yauseyenka, Vassilina; Savasteeva, Irina; Nikonovich, Sergey] Republican Res Ctr Radiat Med & Human Ecol, Gomel, Byelarus.
[Gong, Zhihong] Roswell Pk Canc Inst, Buffalo, NY 14263 USA.
[McConnell, Robert J.] Columbia Univ, Thyroid Ctr, New York, NY USA.
[O'Kane, Patrick] Thomas Jefferson Univ Hosp, Dept Radiol, Philadelphia, PA 19107 USA.
[Brenner, Alina V.; Little, Mark P.; Ostroumova, Evgenia; Bouville, Andre; Drozdovitch, Vladimir; Mabuchi, Kiyohiko; Hatch, Maureen] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Minenko, Viktor] Res Inst Nucl Problems, Minsk, Byelarus.
[Demidchik, Yuri; Nerovnya, Alexander] Belarusian Med Acad Postgrad Educ, Minsk, Byelarus.
RP Zablotska, LB (reprint author), 3333 Calif St,Suite 280, San Francisco, CA 94118 USA.
EM Lydia.Zablotska@ucsf.edu
OI Little, Mark/0000-0003-0980-7567
FU National Cancer Institute [CA132918, NO1-CP-21178]; National Cancer
Institute (Intramural Research Program, Division of Cancer Epidemiology
and Genetics)
FX Funding for this study was provided by the National Cancer Institute
(grant CA132918 to L.B.Z.; contract NO1-CP-21178 to L.B.Z., Z.G., R.J.M.
and P.O; and the Intramural Research Program, Division of Cancer
Epidemiology and Genetics to A.V.B., M.P.L., E.O., A.B., V.D., K.M., and
M.H.).
NR 35
TC 7
Z9 7
U1 1
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0008-543X
EI 1097-0142
J9 CANCER-AM CANCER SOC
JI Cancer
PD FEB 1
PY 2015
VL 121
IS 3
BP 457
EP 466
DI 10.1002/cncr.29073
PG 10
WC Oncology
SC Oncology
GA CB1NP
UT WOS:000349394900020
PM 25351557
ER
PT J
AU Chen, W
Wang, JB
Abnet, CC
Dawsey, SM
Fan, JH
Yin, LY
Yin, J
Taylor, PR
Qiao, YL
Freedman, ND
AF Chen, Wen
Wang, Jian-Bing
Abnet, Christian C.
Dawsey, Sanford M.
Fan, Jin-Hu
Yin, Liang-Yu
Yin, Jian
Taylor, Philip R.
Qiao, You-Lin
Freedman, Neal D.
TI Association between C-Reactive Protein, Incident Liver Cancer, and
Chronic Liver Disease Mortality in the Linxian Nutrition Intervention
Trials: A Nested Case-Control Study
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID HEPATOCELLULAR-CARCINOMA; COLORECTAL-CANCER; OVARIAN-CANCER; RISK;
INFLAMMATION; PROGNOSIS; CIRRHOSIS; SUPPLEMENTATION; MONOCYTES; CHINA
AB Background: C-reactive protein (CRP) is a marker of systemic inflammation that has been associated with the incidence and prognosis for a number of different cancers. Recent data suggest that CRP may be a prognostic factor for liver cancer and cirrhosis. However, few long-term studies are available.
Methods: We prospectively examined associations between serum CRP and subsequent risk of liver cancer incidence or chronic liver disease mortality in a nested case-control study performed in the Linxian Nutrition Intervention Trials cohort. Baseline serum CRP was measured for 220 incident liver cancer cases, 276 participants who died of chronic liver disease, and 1,018 age-, sex-, and trial-matched controls. Unconditional logistical regression models were used to estimate ORs and 95% confidence intervals (CI).
Results: Compared with the lowest quartile, subjects in the fourth quartile of serum CRP had a higher risk of liver cancer incidence (OR, 1.63; 95% CI, 1.06-2.51), with a significant P-trend across quartiles (P = 0.01). The association with liver cancer was only significant among men (Q4 vs. Q1; OR, 2.00; 1.10-3.62), but not among women (Q4 vs. Q1; OR, 1.15; 0.60-2.22). For chronic liver disease deaths, the corresponding risk estimate in men and women was 2.95 (1.90-4.57), with amonotonic trend (P < 0.001).
Conclusions: Higher serum CRP concentrations at baseline were associated with subsequent incidence of liver cancer and death from chronic liver disease.
Impact: Our findings suggest that levels of systemic inflammation may serve as a long-term marker of liver cancer and liver disease. (C) 2015 AACR.
C1 [Chen, Wen; Wang, Jian-Bing; Fan, Jin-Hu; Yin, Jian; Qiao, You-Lin] Chinese Acad Med Sci, Canc Inst Hosp, Dept Canc Epidemiol, Beijing 100730, Peoples R China.
[Chen, Wen; Wang, Jian-Bing; Fan, Jin-Hu; Yin, Jian; Qiao, You-Lin] Peking Union Med Coll, Beijing 100021, Peoples R China.
[Wang, Jian-Bing; Abnet, Christian C.; Dawsey, Sanford M.; Freedman, Neal D.] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD 20850 USA.
[Wang, Jian-Bing] Zhejiang Univ, Sch Publ Hlth, Dept Epidemiol & Hlth Stat, Hangzhou 310003, Zhejiang, Peoples R China.
[Yin, Liang-Yu] Chongqing Med Univ, Sch Publ Hlth, Dept Occupat & Environm Hlth, Chongqing, Peoples R China.
[Taylor, Philip R.] NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD 20850 USA.
RP Freedman, ND (reprint author), NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, 9609 Med Ctr Dr,MSC 9768, Rockville, MD 20850 USA.
EM qiaoy@cicams.ac.cn; freedmanne@mail.nih.gov
RI Freedman, Neal/B-9741-2015; Abnet, Christian/C-4111-2015; Qiao,
You-Lin/B-4139-2012
OI Freedman, Neal/0000-0003-0074-1098; Abnet,
Christian/0000-0002-3008-7843; Qiao, You-Lin/0000-0001-6380-0871
FU National Cancer Institute [N01-SC-91030, N01-RC-47701]; Intramural
Research Program of the Division of Cancer Epidemiology and Genetics;
National Cancer Institute; NIH; Cancer Institute, Chinese Academy of
Medical Sciences
FX This work was supported in part by National Cancer Institute contracts
(N01-SC-91030 and N01-RC-47701) to the Cancer Institute, Chinese Academy
of Medical Sciences; in part by the Intramural Research Program of the
Division of Cancer Epidemiology and Genetics, the National Cancer
Institute, the NIH; and in part by the Cancer Institute, Chinese Academy
of Medical Sciences.
NR 34
TC 2
Z9 2
U1 0
U2 5
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1055-9965
EI 1538-7755
J9 CANCER EPIDEM BIOMAR
JI Cancer Epidemiol. Biomarkers Prev.
PD FEB
PY 2015
VL 24
IS 2
BP 386
EP 392
DI 10.1158/1055-9965.EPI-14-1038
PG 7
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA CB1XY
UT WOS:000349422500009
PM 25613115
ER
PT J
AU Casbas-Hernandez, P
Sun, XZ
Roman-Perez, E
D'Arcy, M
Sandhu, R
Hishida, A
McNaughton, KK
Yang, XHR
Makowski, L
Sherman, ME
Figueroa, JD
Troester, MA
AF Casbas-Hernandez, Patricia
Sun, Xuezheng
Roman-Perez, Erick
D'Arcy, Monica
Sandhu, Rupninder
Hishida, Asahi
McNaughton, Kirk K.
Yang, Xiaohong R.
Makowski, Liza
Sherman, Mark E.
Figueroa, Jonine D.
Troester, Melissa A.
TI Tumor Intrinsic Subtype Is Reflected in Cancer-Adjacent Tissue
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID CARCINOMA-IN-SITU; ESTROGEN-RECEPTOR EXPRESSION; BREAST-CONSERVING
THERAPY; STROMAL-CELL-INTERACTIONS; 20-YEAR FOLLOW-UP; GENE-EXPRESSION;
MOLECULAR CHARACTERIZATION; LOCAL RECURRENCE; MAMMARY-GLAND;
RISK-FACTORS
AB Introduction: Overall survival of early-stage breast cancer patients is similar for those who undergo breast-conserving therapy (BCT) and mastectomy; however, 10% to 15% of women undergoing BCT suffer ipsilateral breast tumor recurrence. The risk of recurrence may vary with breast cancer subtype. Understanding the gene expression of the cancer-adjacent tissue and the stromal response to specific tumor subtypes is important for developing clinical strategies to reduce recurrence risk.
Methods: We utilized two independent datasets to study gene expression data in cancer-adjacent tissue from invasive breast cancer patients. Complementary in vitro cocultures were used to study cell-cell communication between fibroblasts and specific breast cancer subtypes.
Results: Our results suggest that intrinsic tumor subtypes are reflected in histologically normal cancer-adjacent tissue. Gene expression of cancer-adjacent tissues shows that triple-negative (Claudin-low or basal-like) tumors exhibit increased expression of genes involved in inflammation and immune response. Although such changes could reflect distinct immune populations present in the microenvironment, altered immune response gene expression was also observed in cocultures in the absence of immune cell infiltrates, emphasizing that these inflammatory mediators are secreted by breast-specific cells. In addition, although triple-negative breast cancers are associated with upregulated immune response genes, luminal breast cancers are more commonly associated with estrogen-response pathways in adjacent tissues.
Conclusions: Specific characteristics of breast cancers are reflected in the surrounding histologically normal tissue. This commonality between tumor and cancer-adjacent tissue may underlie second primaries and local recurrences.
Impact: Biomarkers derived from cancer-adjacent tissue may be helpful in defining personalized surgical strategies or in predicting recurrence risk. (C)2014 AACR.
C1 [Casbas-Hernandez, Patricia; Troester, Melissa A.] Univ N Carolina, Sch Med, Dept Pathol & Lab Med, Chapel Hill, NC 27599 USA.
[Sun, Xuezheng; Roman-Perez, Erick; D'Arcy, Monica; Troester, Melissa A.] Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Epidemiol, Chapel Hill, NC 27599 USA.
[Sandhu, Rupninder; Hishida, Asahi; Makowski, Liza; Troester, Melissa A.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA.
[McNaughton, Kirk K.] Univ N Carolina, Sch Med, Dept Physiol, Chapel Hill, NC 27599 USA.
[Yang, Xiaohong R.; Sherman, Mark E.; Figueroa, Jonine D.] NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA.
[Makowski, Liza] Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Nutr, Chapel Hill, NC 27599 USA.
RP Troester, MA (reprint author), Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC 27599 USA.
EM troester@unc.edu
RI Hishida, Asahi/C-4888-2016;
OI Hishida, Asahi/0000-0002-4867-0201; Makowski, Liza/0000-0002-5337-8037
FU Avon Foundation; University Cancer Research Fund; National Cancer
Institute [R01CA-138255]; NCI/National Institutes of Environmental
Health Sciences (NIEHS) Breast Cancer; Environment Research Program
(BCERP) [U01-ES-019472]; SPORE Grant [P50-CA-058223]; Howard Hughes
Medical Institute Fellowship; National Cancer Institute Intramural funds
FX X.R. Yang, M.E. Sherman, and J.D. Figueroa received NCI intramural
funds. M.A. Troester received funds from the Avon Foundation, the
University Cancer Research Fund, the National Cancer Institute
(R01CA-138255), the NCI/National Institutes of Environmental Health
Sciences (NIEHS) Breast Cancer and the Environment Research Program
(BCERP; U01-ES-019472), and a SPORE Grant (P50-CA-058223). P.
Casbas-Hernandez was supported by a Howard Hughes Medical Institute
Fellowship. The Polish Breast Cancer Study was supported by the National
Cancer Institute Intramural funds.
NR 49
TC 12
Z9 12
U1 0
U2 1
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1055-9965
EI 1538-7755
J9 CANCER EPIDEM BIOMAR
JI Cancer Epidemiol. Biomarkers Prev.
PD FEB
PY 2015
VL 24
IS 2
BP 406
EP 414
DI 10.1158/1055-9965.EPI-14-0934
PG 9
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA CB1XY
UT WOS:000349422500012
PM 25465802
ER
PT J
AU Marks, JR
Anderson, KS
Engstrom, P
Godwin, AK
Esserman, LJ
Longton, G
Iversen, ES
Mathew, A
Patriotis, C
Pepe, MS
AF Marks, Jeffrey R.
Anderson, Karen S.
Engstrom, Paul
Godwin, Andrew K.
Esserman, Laura J.
Longton, Gary
Iversen, Edwin S.
Mathew, Anu
Patriotis, Christos
Pepe, Margaret S.
TI Construction and Analysis of the NCI-EDRN Breast Cancer Reference Set
for Circulating Markers of Disease
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID ADHESION MOLECULES; BIOMARKERS; POPULATION; MORTALITY; HEALTHY; PROTEIN;
AGE
AB Background: Many circulating biomarkers have been reported for the diagnosis of breast cancer, but few, if any, have undergone rigorous credentialing using prospective cohorts and blinded evaluation.
Methods: The NCI Early Detection Research Network (EDRN) has created a prospective, multicenter collection of plasma and serum samples from 832 subjects designed to evaluate circulating biomarkers for the detection and diagnosis of breast cancer. These samples are available to investigators who wish to evaluate their biomarkers using a set of blinded samples. The breast cancer reference set is composed of blood samples collected using a standard operating procedure at four U.S. medical centers from 2008 to 2010 from women undergoing either tissue diagnosis for breast cancer or routine screening mammography. The reference set contains samples from women with incident invasive cancer (n = 190), carcinoma in situ (n = 55), benign pathology with atypia (n = 63), benign disease with no atypia (n = 231), and women with no evidence of breast disease by screening mammography (BIRADS 1 or 2, n = 276). Using a subset of plasma samples (n = 505) from the reference set, we analyzed 90 proteins by multiplexed immunoassays for their potential utility as diagnostic markers.
Results: We found that none of these markers is useful for distinguishing cancer from benign controls. However, elevated CA-125 does appear to be a candidate marker for estrogen receptor-negative cancers.
Conclusions: Markers that can distinguish benign breast conditions from invasive cancer have not yet been found.
Impact: Availability of prospectively collected samples should improve future validation efforts. (C)2014 AACR.
C1 [Marks, Jeffrey R.] Duke Univ, Dept Surg, Durham, NC 27710 USA.
[Anderson, Karen S.] Arizona State Univ, Biodesign Inst, Ctr Personalized Diagnost, Tempe, AZ USA.
[Engstrom, Paul] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA.
[Godwin, Andrew K.] Univ Kansas, Med Ctr, Dept Pathol & Lab Med, Kansas City, KS 66103 USA.
[Esserman, Laura J.] Univ Calif San Francisco, Dept Surg, San Francisco, CA USA.
[Longton, Gary; Pepe, Margaret S.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Iversen, Edwin S.] Duke Univ, Dept Stat Sci, Durham, NC USA.
[Mathew, Anu] Meso Scale Diagnost LLC, Rockville, MD USA.
[Patriotis, Christos] NCI, NIH, Bethesda, MD 20892 USA.
RP Marks, JR (reprint author), Duke Univ, Med Ctr, Box 3873, Durham, NC 27710 USA.
EM marks003@mc.duke.edu
FU NCI Early Detection Research Network [U01 CA117374, U01 CA113916, UO1
CA084955, UO1 CA111234, U24 CA086368]
FX This work was supported by the NCI Early Detection Research Network (U01
CA117374 to K.S. Anderson; U01 CA113916 to P. Engstrom and A.K. Godwin;
UO1 CA084955 to J.R. Marks; UO1 CA111234 to L.J. Esserman; and U24
CA086368 to M.S. Pepe).
NR 20
TC 1
Z9 1
U1 0
U2 2
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1055-9965
EI 1538-7755
J9 CANCER EPIDEM BIOMAR
JI Cancer Epidemiol. Biomarkers Prev.
PD FEB
PY 2015
VL 24
IS 2
BP 435
EP 441
DI 10.1158/1055-9965.EPI-14-1178
PG 7
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA CB1XY
UT WOS:000349422500015
PM 25471344
ER
PT J
AU Goldszmid, RS
Dzutsev, A
Viaud, S
Zitvogel, L
Restifo, NP
Trinchieri, G
AF Goldszmid, Romina S.
Dzutsev, Amiran
Viaud, Sophie
Zitvogel, Laurence
Restifo, Nicholas P.
Trinchieri, Giorgio
TI Microbiota Modulation of Myeloid Cells in Cancer Therapy
SO CANCER IMMUNOLOGY RESEARCH
LA English
DT Article
ID RECURRENT CLOSTRIDIUM-DIFFICILE; INFLAMMATORY BOWEL DISEASES; CD8(+)
T-CELLS; GUT MICROBIOTA; TUMOR MICROENVIRONMENT; INTESTINAL MICROBIOTA;
COMMENSAL MICROBIOTA; IMMUNITY; RESPONSES; INFECTION
AB Myeloid cells represent a major component of the tumor microenvironment, where they play divergent dual roles. They can induce antitumor immune responses, but mostly they promote immune evasion, tumor progression, and metastasis formation. Thus, strategies aiming at reprogramming the tumor microenvironment represent a promising immunotherapy approach. Myeloid cells respond to environmental factors including signals derived from commensal microbes. In this Cancer Immunology at the Crossroads overview, we discuss recent advances on the effects of the commensal microbiota on myeloid-cell functions and how they affect the response to cancer therapy. (C) 2015 AACR.
C1 [Goldszmid, Romina S.; Dzutsev, Amiran; Trinchieri, Giorgio] NCI, Canc & Inflammat Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Dzutsev, Amiran] Leidos Biomed Res Inc, Bethesda, MD USA.
[Viaud, Sophie; Zitvogel, Laurence] Inst Gustave Roussy, Inst Natl Sante & Rech Med, Villejuif, France.
[Viaud, Sophie; Zitvogel, Laurence] Univ Paris 11, Le Kremlin Bicetre, France.
[Restifo, Nicholas P.] NCI, Surg Branch, Canc Res Ctr, NIH, Bethesda, MD 20892 USA.
RP Trinchieri, G (reprint author), NCI, NIH, Bldg 37,Room 4146, Bethesda, MD 20892 USA.
EM rgoldszmid@mail.nih.gov; trinchig@mail.nih.gov
FU intramural research program of the NCI; Institut National du Cancer
(INCa); la Ligue contre le cancer (LIGUE labellisee); SIRIC Socrate;
LABEX; PACRI Onco-Immunology
FX The work of R.S. Goldszmid, A. Dzutsev, N.P. Restifo, and G. Trinchieri
was supported by the intramural research program of the NCI. The work of
S. Viaud and L. Zitvogel was supported by Institut National du Cancer
(INCa), la Ligue contre le cancer (LIGUE labellisee), SIRIC Socrate,
LABEX, and PACRI Onco-Immunology.
NR 72
TC 7
Z9 9
U1 4
U2 12
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 2326-6066
EI 2326-6074
J9 CANCER IMMUNOL RES
JI Cancer Immunol. Res.
PD FEB
PY 2015
VL 3
IS 2
BP 103
EP 109
DI 10.1158/2326-6066.CIR-14-0225
PG 7
WC Oncology; Immunology
SC Oncology; Immunology
GA CB1XZ
UT WOS:000349422600002
PM 25660553
ER
PT J
AU Yang, H
Cong, WN
Yoon, JS
Egan, JM
AF Yang, Hyekyung
Cong, Wei-na
Yoon, Jeong Seon
Egan, Josephine M.
TI Vismodegib, an antagonist of hedgehog signaling, directly alters taste
molecular signaling in taste buds
SO CANCER MEDICINE
LA English
DT Article
DE Basal-cell carcinoma; sonic hedgehog; taste buds; taste perception;
Vismodegib
ID BASAL-CELL CARCINOMA; SWEET TASTE; PAPILLA DEVELOPMENT; ALPHA-GUSTDUCIN;
DOSE-ESCALATION; NEVUS SYNDROME; UMAMI TASTE; III CELLS; PHASE-I;
PATHWAY
AB Vismodegib, a highly selective inhibitor of hedgehog (Hh) pathway, is an approved treatment for basal-cell carcinoma. Patients on treatment with vismodegib often report profound alterations in taste sensation. The cellular mechanisms underlying the alterations have not been studied. Sonic Hh (Shh) signaling is required for cell growth and differentiation. In taste buds, Shh is exclusively expressed in type IV taste cells, which are undifferentiated basal cells and the precursors of the three types of taste sensing cells. Thus, we investigated if vismodegib has an inhibitory effect on taste cell turnover because of its known effects on Hh signaling. We gavaged C57BL/6J male mice daily with either vehicle or 30mg/kg vismodegib for 15weeks. The gustatory behavior and immunohistochemical profile of taste cells were examined. Vismodegib-treated mice showed decreased growth rate and behavioral responsivity to sweet and bitter stimuli, compared to vehicle-treated mice. We found that vismodegib-treated mice had significant reductions in taste bud size and numbers of taste cells per taste bud. Additionally, vismodegib treatment resulted in decreased numbers of Ki67- and Shh-expressing cells in taste buds. The numbers of phospholipase C2- and -gustducin-expressing cells, which contain biochemical machinery for sweet and bitter sensing, were reduced in vismodegib-treated mice. Furthermore, vismodegib treatment resulted in reduction in numbers of T1R3, glucagon-like peptide-1, and glucagon-expressing cells, which are known to modulate sweet taste sensitivity. These results suggest that inhibition of Shh signaling by vismodegib treatment directly results in alteration of taste due to local effects in taste buds.
C1 [Yang, Hyekyung; Cong, Wei-na; Egan, Josephine M.] NIA, Lab Clin Invest, NIH, Baltimore, MD 21224 USA.
[Yoon, Jeong Seon] NIA, Neurosci Lab, NIH, Baltimore, MD 21224 USA.
RP Egan, JM (reprint author), NIA, Lab Clin Invest, NIH, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM eganj@grc.nia.nih.gov
FU Intramural Research Program of the National Institute on Aging, National
Institutes of Health
FX This research was supported by the Intramural Research Program of the
National Institute on Aging, National Institutes of Health.
NR 47
TC 9
Z9 9
U1 2
U2 11
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 2045-7634
J9 CANCER MED-US
JI Cancer Med.
PD FEB
PY 2015
VL 4
IS 2
BP 245
EP 252
DI 10.1002/cam4.350
PG 8
WC Oncology
SC Oncology
GA CB0IS
UT WOS:000349309800008
PM 25354792
ER
PT J
AU Kaplan, RM
Sun, QK
Ries, AL
AF Kaplan, Robert M.
Sun, Qiankun
Ries, Andrew L.
TI Quality of Well-being Outcomes in the National Emphysema Treatment Trial
SO CHEST
LA English
DT Article
ID VOLUME-REDUCTION SURGERY; OBSTRUCTIVE PULMONARY-DISEASE; OF-LIFE;
LUNG-VOLUME; COST-EFFECTIVENESS; MAJOR DEPRESSION; RANDOMIZED-TRIAL;
CYSTIC-FIBROSIS; SCALE; TRANSPLANTATION
AB BACKGROUND: Surgical and medical treatments for emphysema may affect both quality and quantity of life. The purpose of this article is to report outcomes from the National Emphysema Treatment Trial ( NETT) using an index that combines quality and quantity of life.
METHODS: This was a prospective randomized clinical trial. Following pulmonary rehabilitation, 1,218 patients with severe emphysema were randomly assigned to maximal medical therapy or to lung volume reduction surgery (LVRS). A generic quality-of-life measure, known as the Quality of Well-being Scale (QWB), was administered at baseline and again at 6, 12, 24, 36, 48, 60, and 72 months following treatment assignment.
RESULTS: At baseline, QWB scores were comparable for the Medical and LVRS groups. For both groups, scores significantly improved following the rehabilitation program. The QWB scores before death for patients in the LVRS group improved up to the year 2 visit, whereas scores for the Medical group dropped significantly following the baseline visit. Imputing zeros ( 0) for death, QWB scores decreased significantly for both groups. With or without scoring death as 0, the LVRS group achieved better outcomes, and the significant differences were maintained until the sixth year. Over 6 years of follow-up, LVRS produced an average of 0.30 quality-adjusted life years (QALYs), or the equivalent of about 3.6 months of well life.
CONCLUSIONS: Compared with maximal medical therapy alone, patients undergoing maximal medical therapy plus LVRS experienced improved health-related quality of life and gained more QALYs.
C1 [Kaplan, Robert M.; Sun, Qiankun] NIH, Bethesda, MD 20892 USA.
[Ries, Andrew L.] Univ Calif San Diego, Dept Med, San Diego, CA 92103 USA.
[Ries, Andrew L.] Univ Calif San Diego, Dept Family & Prevent Med, San Diego, CA 92103 USA.
RP Kaplan, RM (reprint author), Agcy Healthcare Res & Qual, 540 Gaither Rd, Rockville, MD 20850 USA.
EM robert.kaplan@ahrq.hhs.gov
FU National Heart, Lung, and Blood Institute [N01HR76101, N01HR76102,
N01HR76103, N01HR76104, N01HR76105, N01HR76106, N01HR76107, N01HR76108,
N01HR76109, N01HR76110, N01HR76111, N01HR76112, N01HR76113, N01HR76114,
N01HR76115, N01HR76116, N01HR76118, N01-HR76119]; Center for Medicare
and Medicaid Services; Agency for Healthcare Research and Quality
FX This study was supported by contracts with the National Heart, Lung, and
Blood Institute [Grants N01HR76101, N01HR76102, N01HR76103, N01HR76104,
N01HR76105, N01HR76106, N01HR76107, N01HR76108, N01HR76109, N01HR76110,
N01HR76111, N01HR76112, N01HR76113, N01HR76114, N01HR76115, N01HR76116,
N01HR76118, and N01-HR76119], the Center for Medicare and Medicaid
Services (formerly the Health Care Financing Administration), and the
Agency for Healthcare Research and Quality.
NR 30
TC 1
Z9 1
U1 0
U2 4
PU AMER COLL CHEST PHYSICIANS
PI GLENVIEW
PA 2595 PATRIOT BLVD, GLENVIEW, IL 60026 USA
SN 0012-3692
J9 CHEST
JI Chest
PD FEB
PY 2015
VL 147
IS 2
BP 377
EP 387
DI 10.1378/chest.14-0528
PG 11
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA CB1YF
UT WOS:000349423200018
PM 25340383
ER
PT J
AU Emoto, C
Fukuda, T
Mizuno, T
Schniedewind, B
Christians, U
Adams, DM
Widemann, BC
Fisher, MJ
Perentesis, J
Weiss, B
Vinks, AA
AF Emoto, C.
Fukuda, T.
Mizuno, T.
Schniedewind, B.
Christians, U.
Adams, D. M.
Widemann, B. C.
Fisher, M. J.
Perentesis, J.
Weiss, B.
Vinks, A. A.
TI AGE-DEPENDENT CHANGES IN CYP3A METABOLIC CAPACITY DETERMINE SIROLIMUS
CLEARANCE IN PEDIATRIC PATIENTS.
SO CLINICAL PHARMACOLOGY & THERAPEUTICS
LA English
DT Meeting Abstract
CT Annual Meeting of the
American-Society-for-Clinical-Pharmacology-and-Therapeutics (ASCPT)
CY MAR 03-07, 2015
CL New Orleans, LA
SP Amer Soc Clin Pharmacol & Therapeut
C1 [Emoto, C.; Fukuda, T.; Mizuno, T.; Vinks, A. A.] Cincinnati Childrens Hosp Med Ctr, Div Clin Pharmacol, Cincinnati, OH 45229 USA.
[Schniedewind, B.; Christians, U.] Univ Colorado, Aurora, CO USA.
[Adams, D. M.; Perentesis, J.; Weiss, B.] Cincinnati Childrens Hosp Med Ctr, Div Oncol, Can & Blood Dis Inst, Cincinnati, OH 45229 USA.
[Widemann, B. C.] NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA.
[Fisher, M. J.] Childrens Hosp Philadelphia, Div Oncol, Philadelphia, PA 19104 USA.
RI Mizuno, Tomoyuki/G-6101-2012
OI Mizuno, Tomoyuki/0000-0002-8471-9826
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0009-9236
EI 1532-6535
J9 CLIN PHARMACOL THER
JI Clin. Pharmacol. Ther.
PD FEB
PY 2015
VL 97
SU 1
MA PII-108
BP S92
EP S93
PG 2
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA CA2HW
UT WOS:000348730500286
ER
PT J
AU Goey, AK
Sissung, TM
Peer, CJ
Ehrlich, S
Balasubramaniam, S
Bryla, C
Bates, SE
Figg, WD
AF Goey, A. K.
Sissung, T. M.
Peer, C. J.
Ehrlich, S.
Balasubramaniam, S.
Bryla, C.
Bates, S. E.
Figg, W. D.
TI EFFECTS OF UGT1A1 GENETIC VARIANTS ON PHARMACOKINETICS AND TOXICITIES OF
BELINOSTAT ADMINSTERED BY CONTINUOUS INFUSION IN COMBINATION WITH
CISPLATIN AND ETOPOSIDE.
SO CLINICAL PHARMACOLOGY & THERAPEUTICS
LA English
DT Meeting Abstract
CT Annual Meeting of the
American-Society-for-Clinical-Pharmacology-and-Therapeutics (ASCPT)
CY MAR 03-07, 2015
CL New Orleans, LA
SP Amer Soc Clin Pharmacol & Therapeut
C1 [Goey, A. K.; Sissung, T. M.; Peer, C. J.; Ehrlich, S.; Balasubramaniam, S.; Bryla, C.; Bates, S. E.; Figg, W. D.] NCI, Bethesda, MD 20892 USA.
RI Figg Sr, William/M-2411-2016
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0009-9236
EI 1532-6535
J9 CLIN PHARMACOL THER
JI Clin. Pharmacol. Ther.
PD FEB
PY 2015
VL 97
SU 1
MA PI-021
BP S27
EP S27
PG 1
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA CA2HW
UT WOS:000348730500074
ER
PT J
AU McCann, DJ
AF McCann, D. J.
TI WHAT IS THE IMPACT OF "PROFESSIONAL SUBJECTS" ON MEDICATION EFFICACY
TRIALS?
SO CLINICAL PHARMACOLOGY & THERAPEUTICS
LA English
DT Meeting Abstract
CT Annual Meeting of the
American-Society-for-Clinical-Pharmacology-and-Therapeutics (ASCPT)
CY MAR 03-07, 2015
CL New Orleans, LA
SP Amer Soc Clin Pharmacol & Therapeut
C1 [McCann, D. J.] NIDA, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0009-9236
EI 1532-6535
J9 CLIN PHARMACOL THER
JI Clin. Pharmacol. Ther.
PD FEB
PY 2015
VL 97
SU 1
MA PI-008
BP S22
EP S23
PG 2
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA CA2HW
UT WOS:000348730500061
ER
PT J
AU Oni-Orisan, A
Edin, ML
Lee, J
Stouffer, GA
Zeldin, DC
Lee, CR
AF Oni-Orisan, A.
Edin, M. L.
Lee, J.
Stouffer, G. A.
Zeldin, D. C.
Lee, C. R.
TI CHARACTERIZATION OF THE RELATIONSHIP BETWEEN BIOMARKERS OF CYTOCHROME
P450-MEDIATED EICOSANOID METABOLISM AND CORONARY ARTERY DISEASE SEVERITY
IN HUMANS.
SO CLINICAL PHARMACOLOGY & THERAPEUTICS
LA English
DT Meeting Abstract
CT Annual Meeting of the
American-Society-for-Clinical-Pharmacology-and-Therapeutics (ASCPT)
CY MAR 03-07, 2015
CL New Orleans, LA
SP Amer Soc Clin Pharmacol & Therapeut
C1 [Oni-Orisan, A.; Lee, J.; Lee, C. R.] Univ N Carolina, Eshelman Sch Pharm, Chapel Hill, NC USA.
[Edin, M. L.; Zeldin, D. C.] NIEHS, Res Triangle Pk, NC 27709 USA.
[Stouffer, G. A.] UNC Sch Med, Chapel Hill, NC USA.
NR 0
TC 0
Z9 0
U1 0
U2 3
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 FEB
PY 2015
VL 97
SU 1
MA OIII-4
BP S103
EP S104
PG 2
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA CA2HW
UT WOS:000348730500315
ER
PT J
AU Oni-Orisan, A
Edin, ML
Lee, J
Stouffer, GA
Zeldin, DC
Lee, CR
AF Oni-Orisan, A.
Edin, M. L.
Lee, J.
Stouffer, G. A.
Zeldin, D. C.
Lee, C. R.
TI CHARACTERIZATION OF THE RELATIONSHIP BETWEEN BIOMARKERS OF CYTOCHROME
P450-MEDIATED EICOSANOID METABOLISM AND CORONARY ARTERY DISEASE SEVERITY
IN HUMANS.
SO CLINICAL PHARMACOLOGY & THERAPEUTICS
LA English
DT Meeting Abstract
CT Annual Meeting of the
American-Society-for-Clinical-Pharmacology-and-Therapeutics (ASCPT)
CY MAR 03-07, 2015
CL New Orleans, LA
SP Amer Soc Clin Pharmacol & Therapeut
C1 [Oni-Orisan, A.; Lee, J.; Lee, C. R.] UNC Eshelman Sch Pharm, Chapel Hill, NC USA.
[Edin, M. L.; Zeldin, D. C.] NIEHS, Res Triangle Pk, NC 27709 USA.
[Stouffer, G. A.] UNC Sch Med, Chapel Hill, NC USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0009-9236
EI 1532-6535
J9 CLIN PHARMACOL THER
JI Clin. Pharmacol. Ther.
PD FEB
PY 2015
VL 97
SU 1
MA PT-07
BP S13
EP S13
PG 1
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA CA2HW
UT WOS:000348730500034
ER
PT J
AU Peer, CJ
Goey, A
Sissung, TM
Ehrlich, S
Bryla, C
Bates, SE
Figg, WD
AF Peer, C. J.
Goey, A.
Sissung, T. M.
Ehrlich, S.
Bryla, C.
Bates, S. E.
Figg, W. D.
TI A POPULATION PHARMACOKINETIC MODEL FOR OPTIMIZED BELINOSTAT DOSING BY
CONTINUOUS INFUSION BASED ON UGT1A1 GENOTYPE.
SO CLINICAL PHARMACOLOGY & THERAPEUTICS
LA English
DT Meeting Abstract
CT Annual Meeting of the
American-Society-for-Clinical-Pharmacology-and-Therapeutics (ASCPT)
CY MAR 03-07, 2015
CL New Orleans, LA
SP Amer Soc Clin Pharmacol & Therapeut
C1 [Peer, C. J.; Goey, A.; Sissung, T. M.; Ehrlich, S.; Bryla, C.; Bates, S. E.; Figg, W. D.] NCI, Bethesda, MD 20892 USA.
RI Figg Sr, William/M-2411-2016
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0009-9236
EI 1532-6535
J9 CLIN PHARMACOL THER
JI Clin. Pharmacol. Ther.
PD FEB
PY 2015
VL 97
SU 1
MA PI-089
BP S47
EP S47
PG 1
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA CA2HW
UT WOS:000348730500142
ER
PT J
AU Sissung, TM
Peer, CJ
Schrump, DS
Figg, WD
AF Sissung, T. M.
Peer, C. J.
Schrump, D. S.
Figg, W. D.
TI PHARMACOGENOMICS OF MITHRAMYCIN-INDUCED HEPTATO-TOXICITY.
SO CLINICAL PHARMACOLOGY & THERAPEUTICS
LA English
DT Meeting Abstract
CT Annual Meeting of the
American-Society-for-Clinical-Pharmacology-and-Therapeutics (ASCPT)
CY MAR 03-07, 2015
CL New Orleans, LA
SP Amer Soc Clin Pharmacol & Therapeut
C1 [Sissung, T. M.; Peer, C. J.; Schrump, D. S.; Figg, W. D.] NCI, Bethesda, MD 20892 USA.
RI Figg Sr, William/M-2411-2016
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0009-9236
EI 1532-6535
J9 CLIN PHARMACOL THER
JI Clin. Pharmacol. Ther.
PD FEB
PY 2015
VL 97
SU 1
MA PII-019
BP S65
EP S65
PG 1
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA CA2HW
UT WOS:000348730500197
ER
PT J
AU Vatsalya, V
Gowin, JL
Schwandt, ML
Momenan, R
Heilig, M
Bardett, SE
Ramchandani, VA
AF Vatsalya, V.
Gowin, J. L.
Schwandt, M. L.
Momenan, R.
Heilig, M.
Bardett, S. E.
Ramchandani, V. A.
TI EFFECTS OF VARENICLINE IN HUMAN LABORATORY MODELS FOR SCREENING
OFPHARMACOTHERAPEUTICS FOR ALCOHOL USE DISORDER.
SO CLINICAL PHARMACOLOGY & THERAPEUTICS
LA English
DT Meeting Abstract
CT Annual Meeting of the
American-Society-for-Clinical-Pharmacology-and-Therapeutics (ASCPT)
CY MAR 03-07, 2015
CL New Orleans, LA
SP Amer Soc Clin Pharmacol & Therapeut
C1 [Vatsalya, V.; Gowin, J. L.; Schwandt, M. L.; Momenan, R.; Heilig, M.; Ramchandani, V. A.] NIAAA, Bethesda, MD USA.
[Bardett, S. E.] Queensland Univ Technol, Brisbane, Qld 4001, Australia.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0009-9236
EI 1532-6535
J9 CLIN PHARMACOL THER
JI Clin. Pharmacol. Ther.
PD FEB
PY 2015
VL 97
SU 1
MA PI-003
BP S21
EP S21
PG 1
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA CA2HW
UT WOS:000348730500056
ER
PT J
AU Yang, H
Ramalingam, S
Kummar, S
Harvey, R
Ivy, P
Beumer, J
AF Yang, H.
Ramalingam, S.
Kummar, S.
Harvey, R.
Ivy, P.
Beumer, J.
TI POPULATION PHARMACOKINETIC AND PHARMACODYNAMIC ANALYSIS OF VORINOSTAT IN
PATIENTS WITH ADVANCED SOLID TUMORS WITH VARYING DEGREES OF HEPATIC
FUNCTION.
SO CLINICAL PHARMACOLOGY & THERAPEUTICS
LA English
DT Meeting Abstract
CT Annual Meeting of the
American-Society-for-Clinical-Pharmacology-and-Therapeutics (ASCPT)
CY MAR 03-07, 2015
CL New Orleans, LA
SP Amer Soc Clin Pharmacol & Therapeut
C1 [Yang, H.; Beumer, J.] Univ Pittsburgh, Pittsburgh, PA USA.
[Ramalingam, S.; Harvey, R.] Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA.
[Kummar, S.] NIH, Clin Ctr Maryland, Bethesda, MD 20892 USA.
[Ivy, P.] NIH, Invest Drug Branch, Pittsburgh, PA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0009-9236
EI 1532-6535
J9 CLIN PHARMACOL THER
JI Clin. Pharmacol. Ther.
PD FEB
PY 2015
VL 97
SU 1
MA PII-029
BP S67
EP S68
PG 2
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA CA2HW
UT WOS:000348730500207
ER
PT J
AU Veleri, S
Lazar, CH
Chang, B
Sieving, PA
Banin, E
Swaroop, A
AF Veleri, Shobi
Lazar, Csilla H.
Chang, Bo
Sieving, Paul A.
Banin, Eyal
Swaroop, Anand
TI Biology and therapy of inherited retinal degenerative disease: insights
from mouse models
SO DISEASE MODELS & MECHANISMS
LA English
DT Review
DE Mouse mutants; Photoreceptor; Retinal development; Retinal disease
ID LEBER CONGENITAL AMAUROSIS; BARDET-BIEDL-SYNDROME; DOMINANT
RETINITIS-PIGMENTOSA; STATIONARY NIGHT BLINDNESS; CONE-ROD DYSTROPHY;
NUCLEAR RECEPTOR NR2E3; HEREDITARY OPTIC NEUROPATHY; LINKED JUVENILE
RETINOSCHISIS; NUCLEOTIDE-GATED CHANNEL; EMBRYONIC STEM-CELLS
AB Retinal neurodegeneration associated with the dysfunction or death of photoreceptors is a major cause of incurable vision loss. Tremendous progress has been made over the last two decades in discovering genes and genetic defects that lead to retinal diseases. The primary focus has now shifted to uncovering disease mechanisms and designing treatment strategies, especially inspired by the successful application of gene therapy in some forms of congenital blindness in humans. Both spontaneous and laboratory-generated mouse mutants have been valuable for providing fundamental insights into normal retinal development and for deciphering disease pathology. Here, we provide a review of mouse models of human retinal degeneration, with a primary focus on diseases affecting photoreceptor function. We also describe models associated with retinal pigment epithelium dysfunction or synaptic abnormalities. Furthermore, we highlight the crucial role of mouse models in elucidating retinal and photoreceptor biology in health and disease, and in the assessment of novel therapeutic modalities, including gene- and stem-cell-based therapies, for retinal degenerative diseases.
C1 [Veleri, Shobi; Lazar, Csilla H.; Banin, Eyal; Swaroop, Anand] NEI, Neurobiol Neurodegenerat & Repair Lab, NIH, Bethesda, MD 20892 USA.
[Lazar, Csilla H.] Univ Babes Bolyai, Mol Biol Ctr, Interdisciplinary Res Inst Bionano Sci, Cluj Napoca 400271, Romania.
[Chang, Bo] Jackson Lab, Bar Harbor, ME 04609 USA.
[Sieving, Paul A.] NEI, NIH, Bethesda, MD 20892 USA.
[Banin, Eyal] Hadassah Hebrew Univ Med Ctr, Dept Ophthalmol, Ctr Retinal & Macular Degenerat, IL-91120 Jerusalem, Israel.
RP Swaroop, A (reprint author), NEI, Neurobiol Neurodegenerat & Repair Lab, NIH, Bethesda, MD 20892 USA.
EM swaroopa@nei.nih.gov
OI Swaroop, Anand/0000-0002-1975-1141
FU National Eye Institute, National Institutes of Health
FX This work is supported by the intramural research program of the
National Eye Institute, National Institutes of Health.
NR 303
TC 27
Z9 27
U1 2
U2 23
PU COMPANY OF BIOLOGISTS LTD
PI CAMBRIDGE
PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL,
CAMBS, ENGLAND
SN 1754-8403
EI 1754-8411
J9 DIS MODEL MECH
JI Dis. Model. Mech.
PD FEB
PY 2015
VL 8
IS 2
BP 109
EP 129
DI 10.1242/dmm.017913
PG 21
WC Cell Biology; Pathology
SC Cell Biology; Pathology
GA CB0SL
UT WOS:000349337200002
PM 25650393
ER
PT J
AU Sue, M
Martucci, V
Frey, F
Lenders, JWM
Timmers, HJ
Peczkowska, M
Prejbisz, A
Swantje, B
Bornstein, SR
Arlt, W
Fassnacht, M
Beuschlein, F
Robledo, M
Pacak, K
Eisenhofer, G
AF Sue, Mariko
Martucci, Victoria
Frey, Florina
Lenders, Jacques W. M.
Timmers, Henri J.
Peczkowska, Mariola
Prejbisz, Aleksander
Swantje, Brede
Bornstein, Stefan R.
Arlt, Wiebke
Fassnacht, Martin
Beuschlein, Felix
Robledo, Mercedes
Pacak, Karel
Eisenhofer, Graeme
TI Lack of utility of SDHB mutation testing in adrenergic metastatic
phaeochromocytoma
SO EUROPEAN JOURNAL OF ENDOCRINOLOGY
LA English
DT Article
ID NON-SYNDROMIC PHEOCHROMOCYTOMA; GERMLINE MUTATIONS; NECK PARAGANGLIOMA;
CLINICAL-PRACTICE; GENE; HEAD
AB Objective: Testing for succinate dehydrogenase subunit B (SDHB) mutations is recommended in all patients with metastatic phaeochromocytomas and paragangliomas (PPGLs), but may not be required when metastatic disease is accompanied by adrenaline production. This retrospective cohort study aimed to establish the prevalence of SDHB mutations among patients with metastatic PPGLs, characterised by production of adrenaline compared with those without production of adrenaline, and to establish genotype-phenotype features of metastatic PPGLs according to underlying gene mutations. Design and methods: Presence of SDHB mutations or deletions was tested in 205 patients (114 males) aged 42 +/- 16 years (range 9-86 years) at diagnosis of metastatic PPGLs with and without adrenaline production.
Results: Twenty-three of the 205 patients (11%) with metastatic PPGLs had disease characterised by production of adrenaline, as defined by increased plasma concentrations of metanephrine larger than 5% of the combined increase in both normetanephrine and metanephrine. None of these 23 patients had SDHB mutations. Of the other 182 patients with no tumoural adrenaline production, 51% had SDHB mutations. Metastases in bone were 36-41% more prevalent among patients with SDHB mutations or extra-adrenal primary tumours than those without mutations or with adrenal primary tumours. Liver metastases were 81% more prevalent among patients with adrenal than extra-adrenal primary tumours. Conclusion: SDHB mutation testing has no utility among patients with adrenaline-producing metastatic PPGLs, but is indicated in other patients with metastatic disease. Our study also reveals novel associations of metastatic spread with primary tumour location and presence of SDHB mutations.
C1 [Sue, Mariko; Bornstein, Stefan R.; Eisenhofer, Graeme] Tech Univ Dresden, Fac Med, Dept Med 3, D-01307 Dresden, Germany.
[Martucci, Victoria; Pacak, Karel] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD 20892 USA.
[Frey, Florina; Eisenhofer, Graeme] Tech Univ Dresden, Fac Med, Inst Clin Chem & Lab Med, D-01307 Dresden, Germany.
[Lenders, Jacques W. M.; Timmers, Henri J.] Radboud Univ Nijmegen, Med Ctr, Dept Internal Med, NL-6525 GA Nijmegen, Netherlands.
[Peczkowska, Mariola; Prejbisz, Aleksander] Inst Cardiol, Dept Hypertens, PL-04628 Warsaw, Poland.
[Swantje, Brede] Univ Lubeck, Dept Neuroendocrinol, D-23562 Lubeck, Germany.
[Arlt, Wiebke] Univ Birmingham, Inst Biomed Res, Sch Clin & Expt Med, Ctr Endocrinol Diabet & Metab, Birmingham B15 2TT, W Midlands, England.
[Fassnacht, Martin] Univ Wurzburg, Univ Hosp, D-97080 Wurzburg, Germany.
[Fassnacht, Martin] Univ Wurzburg, Comprehens Canc Ctr Mainfranken, D-97080 Wurzburg, Germany.
[Beuschlein, Felix] Klinikum Univ Munchen, Med Klin & Poliklin 4, Endocrine Res Unit, D-80336 Munich, Germany.
[Robledo, Mercedes] Hereditary Endocrine Canc Grp, Spanish Natl Canc Res Ctr Med CNIO, Madrid 28029, Spain.
RP Sue, M (reprint author), Tech Univ Dresden, Fac Med, Dept Med 3, Fetscherstr 74, D-01307 Dresden, Germany.
EM Mariko.Sue@uniklinikum-dresden.de
RI Arlt, Wiebke/B-6310-2009; Lenders, J.W.M./L-4487-2015
OI Arlt, Wiebke/0000-0001-5106-9719;
FU Deutsche Forschungsgemeinschaft [EI855/1/1]; Polish Ministry of Science
and Higher Education [N N402 386038]; European Union Seventh Framework
Programme (FP7) [259735]
FX This study was supported by the Deutsche Forschungsgemeinschaft
(EI855/1/1), the Polish Ministry of Science and Higher Education (N N402
386038), and the European Union Seventh Framework Programme
(FP7/2007-2013) under grant agreement 259735 (ENS@T-Cancer).
NR 22
TC 0
Z9 0
U1 0
U2 0
PU BIOSCIENTIFICA LTD
PI BRISTOL
PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT,
ENGLAND
SN 0804-4643
EI 1479-683X
J9 EUR J ENDOCRINOL
JI Eur. J. Endocrinol.
PD FEB
PY 2015
VL 172
IS 2
DI 10.1530/EJE-14-0756
PG 7
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA CB2LD
UT WOS:000349458000005
ER
PT J
AU Li, Q
Wojciechowski, R
Simpson, CL
Hysi, PG
Verhoeven, VJM
Ikram, MK
Hohn, R
Vitart, V
Hewitt, AW
Oexle, K
Makela, KM
MacGregor, S
Pirastu, M
Fan, Q
Cheng, CY
St Pourcain, B
McMahon, G
Kemp, JP
Northstone, K
Rahi, JS
Cumberland, PM
Martin, NG
Sanfilippo, PG
Lu, Y
Wang, YX
Hayward, C
Polasek, O
Campbell, H
Bencic, G
Wright, AF
Wedenoja, J
Zeller, T
Schillert, A
Mirshahi, A
Lackner, K
Yip, SP
Yap, MKH
Ried, JS
Gieger, C
Murgia, F
Wilson, JF
Fleck, B
Yazar, S
Vingerling, JR
Hofman, A
Uitterlinden, A
Rivadeneira, F
Amin, N
Karssen, L
Oostra, BA
Zhou, X
Teo, YY
Tai, ES
Vithana, E
Barathi, V
Zheng, YF
Siantar, RG
Neelam, K
Shin, YC
Lam, J
Yonova-Doing, E
Venturini, C
Hosseini, SM
Wong, HS
Lehtimaki, T
Kahonen, M
Raitakari, O
Timpson, NJ
Evans, DM
Khor, CC
Aung, T
Young, TL
Mitchell, P
Klein, B
van Duijn, CM
Meitinger, T
Jonas, JB
Baird, PN
Mackey, DA
Wong, TY
Saw, SM
Parssinen, O
Stambolian, D
Hammond, CJ
Klaver, CCW
Williams, C
Paterson, AD
Bailey-Wilson, JE
Guggenheim, JA
AF Li, Qing
Wojciechowski, Robert
Simpson, Claire L.
Hysi, Pirro G.
Verhoeven, Virginie J. M.
Ikram, Mohammad Kamran
Hoehn, Rene
Vitart, Veronique
Hewitt, Alex W.
Oexle, Konrad
Makela, Kari-Matti
MacGregor, Stuart
Pirastu, Mario
Fan, Qiao
Cheng, Ching-Yu
St Pourcain, Beat
McMahon, George
Kemp, John P.
Northstone, Kate
Rahi, Jugnoo S.
Cumberland, Phillippa M.
Martin, Nicholas G.
Sanfilippo, Paul G.
Lu, Yi
Wang, Ya Xing
Hayward, Caroline
Polasek, Ozren
Campbell, Harry
Bencic, Goran
Wright, Alan F.
Wedenoja, Juho
Zeller, Tanja
Schillert, Arne
Mirshahi, Alireza
Lackner, Karl
Yip, Shea Ping
Yap, Maurice K. H.
Ried, Janina S.
Gieger, Christian
Murgia, Federico
Wilson, James F.
Fleck, Brian
Yazar, Seyhan
Vingerling, Johannes R.
Hofman, Albert
Uitterlinden, Andre
Rivadeneira, Fernando
Amin, Najaf
Karssen, Lennart
Oostra, Ben A.
Zhou, Xin
Teo, Yik-Ying
Tai, E. Shyong
Vithana, Eranga
Barathi, Veluchamy
Zheng, Yingfeng
Siantar, Rosalynn Grace
Neelam, Kumari
Shin, Youchan
Lam, Janice
Yonova-Doing, Ekaterina
Venturini, Cristina
Hosseini, S. Mohsen
Wong, Hoi-Suen
Lehtimaki, Terho
Kahonen, Mika
Raitakari, Olli
Timpson, Nicholas J.
Evans, David M.
Khor, Chiea-Chuen
Aung, Tin
Young, Terri L.
Mitchell, Paul
Klein, Barbara
van Duijn, Cornelia M.
Meitinger, Thomas
Jonas, Jost B.
Baird, Paul N.
Mackey, David A.
Wong, Tien Yin
Saw, Seang-Mei
Parssinen, Olavi
Stambolian, Dwight
Hammond, Christopher J.
Klaver, Caroline C. W.
Williams, Cathy
Paterson, Andrew D.
Bailey-Wilson, Joan E.
Guggenheim, Jeremy A.
CA CREAM Consortium
TI Genome-wide association study for refractive astigmatism reveals genetic
co-determination with spherical equivalent refractive error: the CREAM
consortium
SO HUMAN GENETICS
LA English
DT Article
ID EXPERIMENTALLY-INDUCED MYOPIA; OPEN-ANGLE GLAUCOMA; BLUE MOUNTAINS EYE;
CORNEAL ASTIGMATISM; SUSCEPTIBILITY LOCI; NONCODING RNAS; MAJOR LOCUS;
POPULATION; AGE; DISEASE
AB To identify genetic variants associated with refractive astigmatism in the general population, meta-analyses of genome-wide association studies were performed for: White Europeans aged at least 25 years (20 cohorts, N = 31,968); Asian subjects aged at least 25 years (7 cohorts, N = 9,295); White Europeans aged < 25 years (4 cohorts, N = 5,640); and all independent individuals from the above three samples combined with a sample of Chinese subjects aged < 25 years (N = 45,931). Participants were classified as cases with refractive astigmatism if the average cylinder power in their two eyes was at least 1.00 diopter and as controls otherwise. Genome-wide association analysis was carried out for each cohort separately using logistic regression. Meta-analysis was conducted using a fixed effects model. In the older European group the most strongly associated marker was downstream of the neurexin-1 (NRXN1) gene (rs1401327, P = 3.92E-8). No other region reached genome-wide significance, and association signals were lower for the younger European group and Asian group. In the meta-analysis of all cohorts, no marker reached genome-wide significance: The most strongly associated regions were, NRXN1 (rs1401327, P = 2.93E-07), TOX (rs7823467, P = 3.47E-07) and LINC00340 (rs12212674, P = 1.49E-06). For 34 markers identified in prior GWAS for spherical equivalent refractive error, the beta coefficients for genotype versus spherical equivalent, and genotype versus refractive astigmatism, were highly correlated (r = -0.59, P = 2.10E-04). This work revealed no consistent or strong genetic signals for refractive astigmatism; however, the TOX gene region previously identified in GWAS for spherical equivalent refractive error was the second most strongly associated region. Analysis of additional markers provided evidence supporting widespread genetic co-susceptibility for spherical and astigmatic refractive errors.
C1 [Li, Qing; Wojciechowski, Robert; Simpson, Claire L.; Bailey-Wilson, Joan E.] NHGRI, NIH, Baltimore, MD 21224 USA.
[Wojciechowski, Robert] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Wojciechowski, Robert] Johns Hopkins Med Inst, Wilmer Eye Inst, Baltimore, MD 21205 USA.
[Hysi, Pirro G.; Yonova-Doing, Ekaterina; Venturini, Cristina; Hammond, Christopher J.] Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England.
[Verhoeven, Virginie J. M.; Vingerling, Johannes R.; Klaver, Caroline C. W.] Erasmus MC, Dept Ophthalmol, Rotterdam, Netherlands.
[Verhoeven, Virginie J. M.; Hofman, Albert; Uitterlinden, Andre; Rivadeneira, Fernando; Amin, Najaf; Karssen, Lennart; van Duijn, Cornelia M.; Klaver, Caroline C. W.] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.
[Ikram, Mohammad Kamran; Cheng, Ching-Yu; Vithana, Eranga; Barathi, Veluchamy; Zheng, Yingfeng; Siantar, Rosalynn Grace; Neelam, Kumari; Shin, Youchan; Lam, Janice; Aung, Tin; Wong, Tien Yin; Saw, Seang-Mei] Singapore Eye Res Inst, Singapore, Singapore.
[Ikram, Mohammad Kamran; Cheng, Ching-Yu; Vithana, Eranga; Barathi, Veluchamy; Khor, Chiea-Chuen; Wong, Tien Yin; Saw, Seang-Mei] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Ophthalmol, Singapore 117595, Singapore.
[Ikram, Mohammad Kamran; Cheng, Ching-Yu; Wong, Tien Yin] Duke NUS Grad Med Sch, Off Clin Sci, Singapore, Singapore.
[Hoehn, Rene; Mirshahi, Alireza] Univ Med Ctr Mainz, Dept Ophthalmol, Mainz, Germany.
[Hoehn, Rene] Klin Pallas, Olten, Switzerland.
[Vitart, Veronique; Hayward, Caroline; Wright, Alan F.] Univ Edinburgh, Inst Genet & Mol Med, Med Res Council Human Genet Unit, Edinburgh EH4 2XU, Midlothian, Scotland.
[Hewitt, Alex W.; Baird, Paul N.; Mackey, David A.] Univ Melbourne, Royal Victorian Eye & Ear Hosp, Ctr Eye Res Australia, Melbourne, Vic, Australia.
[Hewitt, Alex W.; Sanfilippo, Paul G.; Yazar, Seyhan; Mackey, David A.] Univ Western Australia, Lions Eye Inst, Ctr Ophthalmol & Visual Sci, Perth, WA 6009, Australia.
[Oexle, Konrad; Meitinger, Thomas] Tech Univ Munich, Klinikum Rechts Isar, Inst Human Genet, D-80290 Munich, Germany.
[Makela, Kari-Matti; Lehtimaki, Terho] Tampere Univ Hosp, Dept Clin Chem, Tampere 33520, Finland.
[Makela, Kari-Matti; Lehtimaki, Terho] Univ Tampere, Sch Med, Tampere 33520, Finland.
[MacGregor, Stuart; Lu, Yi] Royal Brisbane Hosp, QIMR Berghofer Med Res Inst, Brisbane, Qld 4029, Australia.
[Pirastu, Mario; Murgia, Federico] CNR, Inst Populat Genet, I-07040 Sassari, Italy.
[Fan, Qiao; Zhou, Xin; Teo, Yik-Ying; Tai, E. Shyong; Saw, Seang-Mei] Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore 117548, Singapore.
[St Pourcain, Beat; McMahon, George; Kemp, John P.; Timpson, Nicholas J.; Evans, David M.] Univ Bristol, MRC Integrat Epidemiol Unit IEU, Bristol BS8 2BN, Avon, England.
[St Pourcain, Beat; McMahon, George; Kemp, John P.; Northstone, Kate; Timpson, Nicholas J.; Evans, David M.; Williams, Cathy] Univ Bristol, Sch Social & Community Med, Bristol BS8 2BN, Avon, England.
[Rahi, Jugnoo S.; Cumberland, Phillippa M.] UCL Inst Child Hlth, Ctr Epidemiol & Biostat, London, England.
[Rahi, Jugnoo S.; Venturini, Cristina] UCL, Inst Ophthalmol, London, England.
[Rahi, Jugnoo S.; Cumberland, Phillippa M.] UCL Inst Child Hlth, Ulverscroft Vis Res Grp, London, England.
[Martin, Nicholas G.] Royal Brisbane Hosp, QIMR Berghofer Med Res Inst, Brisbane, Qld 4029, Australia.
[Wang, Ya Xing] Capital Univ Med Sci, Beijing Tongren Hosp, Beijing Inst Ophthalmol, Beijing, Peoples R China.
[Polasek, Ozren] Univ Split, Fac Med, Split, Croatia.
[Campbell, Harry; Wilson, James F.] Univ Edinburgh, Ctr Populat Hlth Sci, Edinburgh EH8 9AG, Midlothian, Scotland.
[Bencic, Goran] Sisters Mercy Univ Hosp, Dept Ophthalmol, Zagreb, Croatia.
[Wedenoja, Juho] Univ Helsinki, Hjelt Inst, Dept Publ Hlth, Helsinki, Finland.
[Wedenoja, Juho] Univ Helsinki, Cent Hosp, Dept Ophthalmol, Helsinki, Finland.
[Zeller, Tanja] Univ Heart Ctr Hamburg, Clin Gen & Intervent Cardiol, Hamburg, Germany.
[Schillert, Arne] Med Univ Lubeck, Univ Hosp Schleswig Holstein, Inst Med Biometry & Stat, D-23538 Lubeck, Germany.
[Schillert, Arne] DZHK German Ctr Cardiovasc Res, Lubeck, Germany.
[Mirshahi, Alireza] Dardenne Eye Hosp, Bonn, Germany.
[Lackner, Karl] Univ Med Ctr Mainz, Inst Clin Chem & Lab Med, Mainz, Germany.
[Yip, Shea Ping] Hong Kong Polytech Univ, Dept Hlth Technol & Informat, Hong Kong, Hong Kong, Peoples R China.
[Yip, Shea Ping; Yap, Maurice K. H.; Guggenheim, Jeremy A.] Hong Kong Polytech Univ, Sch Optometry, Ctr Myopia Res, Kowloon, Hong Kong, Peoples R China.
[Ried, Janina S.; Gieger, Christian] Helmholtz Zentrum Munchen, Inst Genet Epidemiol, Neuherberg, Germany.
[Fleck, Brian] Princess Alexandra Eye Pavil, Edinburgh EH3 9HA, Midlothian, Scotland.
[Hofman, Albert; Uitterlinden, Andre; Rivadeneira, Fernando] Netherlands Genom Initiat, Netherlands Consortium Hlth Ageing, The Hague, Netherlands.
[Uitterlinden, Andre; Rivadeneira, Fernando] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands.
[Oostra, Ben A.] Erasmus MC, Dept Clin Genet, Rotterdam, Netherlands.
[Teo, Yik-Ying] Natl Univ Singapore, Dept Stat & Appl Probabil, Singapore 117548, Singapore.
[Tai, E. Shyong] Natl Univ Singapore, Dept Med, Singapore 117548, Singapore.
[Tai, E. Shyong] Natl Univ Hlth Syst, Singapore, Singapore.
[Tai, E. Shyong; Barathi, Veluchamy; Young, Terri L.; Saw, Seang-Mei] Duke Natl Univ Singapore Grad Med Sch, Singapore, Singapore.
[Vithana, Eranga] Duke NUS Grad Med Sch, NBD Program, Singapore, Singapore.
[Hosseini, S. Mohsen; Wong, Hoi-Suen; Paterson, Andrew D.] Hosp Sick Children Res Inst, Genet & Genome Biol Program, Toronto, ON M5G 0A4, Canada.
[Kahonen, Mika] Tampere Univ Hosp, Dept Clin Physiol, Tampere 33521, Finland.
[Kahonen, Mika] Univ Tampere, Sch Med, Tampere 33521, Finland.
[Raitakari, Olli] Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, Turku, Finland.
[Raitakari, Olli] Turku Univ Hosp, Dept Clin Physiol & Nucl Med, Turku 20041, Finland.
[Evans, David M.] Univ Queensland, Diamantina Inst, Translat Res Inst, Brisbane, Qld, Australia.
[Khor, Chiea-Chuen] Genome Inst Singapore, Div Human Genet, Singapore, Singapore.
[Young, Terri L.] Duke Univ, Sch Med, Duke Eye Ctr, Durham, NC USA.
[Mitchell, Paul] Univ Sydney, Sydney, NSW 2006, Australia.
[Mitchell, Paul] Western Sydney Local Hlth Network, Sydney, NSW, Australia.
[Mitchell, Paul] Westmead Millennium Inst, Westmead, NSW, Australia.
[Klein, Barbara] Univ Wisconsin Madison, Madison, WI 53726 USA.
[Jonas, Jost B.] Capital Med Univ, Beijing Ophthalmol & Visual Sci Key Lab, Beijing Tongren Hosp, Beijing Inst Ophthalmol,Beijing Tongren Eye Ctr, Beijing, Peoples R China.
[Jonas, Jost B.] Heidelberg Univ, Med Fac Mannheim, Dept Ophthalmol, Mannheim, Germany.
[Parssinen, Olavi] Univ Jyvaskyla, Dept Hlth Sci, Jyvaskyla, Finland.
[Parssinen, Olavi] Univ Jyvaskyla, Gerontol Res Ctr, Jyvaskyla, Finland.
[Parssinen, Olavi] Cent Hosp Cent Finland, Dept Ophthalmol, Jyvaskyla, Finland.
[Stambolian, Dwight] Univ Penn, Sch Med, Philadelphia, PA 19104 USA.
[Hammond, Christopher J.] Kings Coll London, Dept Ophthalmol, London, England.
[Paterson, Andrew D.] Univ Toronto, Dala Lanna Sch Publ Hlth, Toronto, ON, Canada.
RP Guggenheim, JA (reprint author), Hong Kong Polytech Univ, Sch Optometry, Ctr Myopia Res, Kowloon, Hong Kong, Peoples R China.
EM jeremy.guggenheim@polyu.edu.hk
RI wang, YA XING/K-9671-2016; Mackey, David/H-5340-2014; Northstone,
Kate/A-8165-2011; Paterson, Andrew/A-4088-2011; Hewitt,
Alex/D-1936-2013; Yap, Maurice/K-4927-2016; Delcourt,
Cecile/I-2627-2013; Macgregor, Stuart/C-6442-2009; DeAngelis,
e/J-7863-2015; Mitchell, Paul/P-1498-2014; Wilson, James F/A-5704-2009;
Polasek, Ozren/B-6002-2011; Meitinger, Thomas/O-1318-2015; Biino,
Ginevra/B-5334-2013; Rivadeneira, Fernando/O-5385-2015; Yip, Shea
Ping/A-1185-2016;
OI wang, YA XING/0000-0003-2749-7793; Mackey, David/0000-0001-7914-4709;
Northstone, Kate/0000-0002-0602-1983; Simpson,
Claire/0000-0003-2244-7690; Yazar, Seyhan/0000-0003-0994-6196;
Wojciechowski, Robert/0000-0002-9593-4652; Bailey-Wilson,
Joan/0000-0002-9153-2920; Baird, Paul/0000-0002-1305-3502; Hosseini,
Mohsen/0000-0003-3626-9928; Gieger, Christian/0000-0001-6986-9554;
Luben, Robert/0000-0002-5088-6343; Rantanen, Taina/0000-0002-1604-1945;
Gharahkhani, Puya/0000-0002-4203-5952; Hohn, Rene /0000-0003-2870-1469;
St Pourcain, Beate/0000-0002-4680-3517; Khor, Chiea
Chuen/0000-0002-1128-4729; Hammond, Christopher/0000-0002-3227-2620;
Paterson, Andrew/0000-0002-9169-118X; Hewitt, Alex/0000-0002-5123-5999;
Yap, Maurice/0000-0003-4687-4101; Delcourt, Cecile/0000-0002-2099-0481;
Macgregor, Stuart/0000-0001-6731-8142; Wilson, James
F/0000-0001-5751-9178; Polasek, Ozren/0000-0002-5765-1862; Biino,
Ginevra/0000-0002-9936-946X; Rivadeneira, Fernando/0000-0001-9435-9441;
Yip, Shea Ping/0000-0002-2170-8185; Kemp, John/0000-0002-9105-2249;
Ikram, Mohammad Kamran/0000-0003-0173-9571; Evans,
David/0000-0003-0663-4621; Tai, E Shyong/0000-0003-2929-8966; Karssen,
Lennart C./0000-0002-1959-342X
FU Chief Scientist Office [CZB/4/438, CZB/4/710]; Department of Health
[CDF-2009-02-35, SRF/01/010]; Intramural NIH HHS [Z99 EY999999]; Medical
Research Council [MC_PC_15018, MC_PC_U127561128, MC_UU_12013/3,
MC_UU_12013/4]; NEI NIH HHS [K08 EY022943, P30 EY001583, R01 EY014685,
R01 EY024233]; Wellcome Trust [102215]
NR 93
TC 3
Z9 3
U1 1
U2 13
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0340-6717
EI 1432-1203
J9 HUM GENET
JI Hum. Genet.
PD FEB
PY 2015
VL 134
IS 2
BP 131
EP 146
DI 10.1007/s00439-014-1500-y
PG 16
WC Genetics & Heredity
SC Genetics & Heredity
GA AZ3TM
UT WOS:000348149500001
PM 25367360
ER
PT J
AU Carvajal-Carmona, LG
O'Mara, TA
Painter, JN
Lose, FA
Dennis, J
Michailidou, K
Tyrer, JP
Ahmed, S
Ferguson, K
Healey, CS
Pooley, K
Beesley, J
Cheng, T
Jones, A
Howarth, K
Martin, L
Gorman, M
Hodgson, S
Wentzensen, N
Fasching, PA
Hein, A
Beckmann, MW
Renner, SP
Dork, T
Hillemanns, P
Durst, M
Runnebaum, I
Lambrechts, D
Coenegrachts, L
Schrauwen, S
Amant, F
Winterhoff, B
Dowdy, SC
Goode, EL
Teoman, A
Salvesen, HB
Trovik, J
Njolstad, TS
Werner, HMJ
Scott, RJ
Ashton, K
Proietto, T
Otton, G
Wersall, O
Mints, M
Tham, E
Hall, P
Czene, K
Liu, JJ
Li, JM
Hopper, JL
Southey, MC
Ekici, AB
Ruebner, M
Johnson, N
Peto, J
Burwinkel, B
Marme, F
Brenner, H
Dieffenbach, AK
Meindl, A
Brauch, H
Lindblom, A
Depreeuw, J
Moisse, M
Chang-Claude, J
Rudolph, A
Couch, FJ
Olson, JE
Giles, GG
Bruinsma, F
Cunningham, JM
Fridley, BL
Borresen-Dale, AL
Kristensen, VN
Cox, A
Swerdlow, AJ
Orr, N
Bolla, MK
Wang, Q
Weber, RP
Chen, ZH
Shah, M
Pharoah, PDP
Dunning, AM
Tomlinson, I
Easton, DF
Spurdle, AB
Thompson, DJ
AF Carvajal-Carmona, Luis G.
O'Mara, Tracy A.
Painter, Jodie N.
Lose, Felicity A.
Dennis, Joe
Michailidou, Kyriaki
Tyrer, Jonathan P.
Ahmed, Shahana
Ferguson, Kaltin
Healey, Catherine S.
Pooley, Karen
Beesley, Jonathan
Cheng, Timothy
Jones, Angela
Howarth, Kimberley
Martin, Lynn
Gorman, Maggie
Hodgson, Shirley
Wentzensen, Nicholas
Fasching, Peter A.
Hein, Alexander
Beckmann, Matthias W.
Renner, Stefan P.
Doerk, Thilo
Hillemanns, Peter
Duerst, Matthias
Runnebaum, Ingo
Lambrechts, Diether
Coenegrachts, Lieve
Schrauwen, Stefanie
Amant, Frederic
Winterhoff, Boris
Dowdy, Sean C.
Goode, Ellen L.
Teoman, Attila
Salvesen, Helga B.
Trovik, Jone
Njolstad, Tormund S.
Werner, Henrica M. J.
Scott, Rodney J.
Ashton, Katie
Proietto, Tony
Otton, Geoffrey
Wersaell, Ofra
Mints, Miriam
Tham, Emma
Hall, Per
Czene, Kamila
Liu, Jianjun
Li, Jingmei
Hopper, John L.
Southey, Melissa C.
Ekici, Arif B.
Ruebner, Matthias
Johnson, Nichola
Peto, Julian
Burwinkel, Barbara
Marme, Frederik
Brenner, Hermann
Dieffenbach, Aida K.
Meindl, Alfons
Brauch, Hiltrud
Lindblom, Annika
Depreeuw, Jeroen
Moisse, Matthieu
Chang-Claude, Jenny
Rudolph, Anja
Couch, Fergus J.
Olson, Janet E.
Giles, Graham G.
Bruinsma, Fiona
Cunningham, Julie M.
Fridley, Brooke L.
Borresen-Dale, Anne-Lise
Kristensen, Vessela N.
Cox, Angela
Swerdlow, Anthony J.
Orr, Nicholas
Bolla, Manjeet K.
Wang, Qin
Weber, Rachel Palmieri
Chen, Zhihua
Shah, Mitul
Pharoah, Paul D. P.
Dunning, Alison M.
Tomlinson, Ian
Easton, Douglas F.
Spurdle, Amanda B.
Thompson, Deborah J.
CA NSECG
ANECS
RENDOCAS
AOCS
GENICA Network
TI Candidate locus analysis of the TERT-CLPTM1L cancer risk region on
chromosome 5p15 identifies multiple independent variants associated with
endometrial cancer risk
SO HUMAN GENETICS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; SUSCEPTIBILITY LOCI; PROSTATE-CANCER;
BREAST-CANCER; OVARIAN-CANCER; FUNCTIONAL VARIATION; TELOMERE LENGTH;
COMMON VARIANT; EXPRESSION; GENE
AB Several studies have reported associations between multiple cancer types and single-nucleotide polymorphisms (SNPs) on chromosome 5p15, which harbours TERT and CLPTM1L, but no such association has been reported with endometrial cancer. To evaluate the role of genetic variants at the TERT-CLPTM1L region in endometrial cancer risk, we carried out comprehensive fine-mapping analyses of genotyped and imputed SNPs using a custom Illumina iSelect array which includes dense SNP coverage of this region. We examined 396 SNPs (113 genotyped, 283 imputed) in 4,401 endometrial cancer cases and 28,758 controls. Single-SNP and forward/backward logistic regression models suggested evidence for three variants independently associated with endometrial cancer risk (P = 4.9 x 10(-6) to P = 7.7 x 10(-5)). Only one falls into a haplotype previously associated with other cancer types (rs7705526, in TERT intron 1), and this SNP has been shown to alter TERT promoter activity. One of the novel associations (rs13174814) maps to a second region in the TERT promoter and the other (rs62329728) is in the promoter region of CLPTM1L; neither are correlated with previously reported cancer-associated SNPs. Using TCGA RNASeq data, we found significantly increased expression of both TERT and CLPTM1L in endometrial cancer tissue compared with normal tissue (TERT P = 1.5 x 10(-18), CLPTM1L P = 1.5 x 10(-19)). Our study thus reports a novel endometrial cancer risk locus and expands the spectrum of cancer types associated with genetic variation at 5p15, further highlighting the importance of this region for cancer susceptibility.
C1 [Carvajal-Carmona, Luis G.] Univ Calif Davis, Sch Med, Genome Ctr, Davis, CA 95616 USA.
[Carvajal-Carmona, Luis G.] Univ Calif Davis, Sch Med, Dept Biochem & Mol Med, Davis, CA 95616 USA.
[O'Mara, Tracy A.; Painter, Jodie N.; Lose, Felicity A.; Ferguson, Kaltin; Beesley, Jonathan; Spurdle, Amanda B.; ANECS] QIMR Berghofer Med Res Inst, Australian Ovarian Canc Study AOCS, Australian Natl Endometrial Canc Study Grp ANECS, Brisbane, Qld, Australia.
[Dennis, Joe; Michailidou, Kyriaki; Pooley, Karen; Bolla, Manjeet K.; Wang, Qin; Easton, Douglas F.; Thompson, Deborah J.] Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Publ Hlth & Primary Care, Cambridge, England.
[Tyrer, Jonathan P.; Ahmed, Shahana; Healey, Catherine S.; Shah, Mitul; Pharoah, Paul D. P.; Dunning, Alison M.; Easton, Douglas F.] Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Oncol, Cambridge, England.
[Cheng, Timothy; Jones, Angela; Howarth, Kimberley; Martin, Lynn; Gorman, Maggie; Tomlinson, Ian; NSECG] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.
[Hodgson, Shirley] St Georges Hosp Med Sch, Dept Clin Genet, London, England.
[Wentzensen, Nicholas] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Fasching, Peter A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Hematol Oncol, Los Angeles, CA 90095 USA.
[Fasching, Peter A.; Hein, Alexander; Beckmann, Matthias W.; Renner, Stefan P.; Ekici, Arif B.; Ruebner, Matthias] Univ Erlangen Nurnberg, Univ Hosp Erlangen, Dept Gynecol & Obstet, D-91054 Erlangen, Germany.
[Doerk, Thilo] Hannover Med Sch, Gynaecol Res Unit, Hannover, Germany.
[Hillemanns, Peter] Hannover Med Sch, Clin Gynaecol, Hannover, Germany.
[Hillemanns, Peter] Hannover Med Sch, Clin Obstet, Hannover, Germany.
[Duerst, Matthias; Runnebaum, Ingo] Univ Jena, Jena Univ Hosp, Dept Gynaecol, Jena, Germany.
[Lambrechts, Diether; Depreeuw, Jeroen; Moisse, Matthieu] VIB, Vesalius Res Ctr, Leuven, Belgium.
[Lambrechts, Diether; Depreeuw, Jeroen; Moisse, Matthieu] Katholieke Univ Leuven, Lab Translat Genet, Dept Oncol, Leuven, Belgium.
[Coenegrachts, Lieve; Schrauwen, Stefanie; Amant, Frederic] Katholieke Univ Leuven, Dept Oncol, Leuven, Belgium.
[Amant, Frederic] Univ Hosp Leuven, Div Gynaecol Oncol, Leuven, Belgium.
[Winterhoff, Boris; Dowdy, Sean C.; Teoman, Attila] Mayo Clin, Dept Obstet & Gynecol, Div Gynecol Oncol, Rochester, MN USA.
[Goode, Ellen L.; Olson, Janet E.] Mayo Clin, Dept Hlth Sci Res, Div Epidemiol, Rochester, MN USA.
[Salvesen, Helga B.; Trovik, Jone; Njolstad, Tormund S.; Werner, Henrica M. J.] Univ Bergen, Dept Clin Sci, Ctr Cancerbiomarkers, Bergen, Norway.
[Salvesen, Helga B.; Trovik, Jone; Njolstad, Tormund S.; Werner, Henrica M. J.] Haukeland Hosp, Dept Obstet & Gynecol, N-5021 Bergen, Norway.
[Scott, Rodney J.; Ashton, Katie] John Hunter Hosp, Hunter Med Res Inst, Newcastle, NSW, Australia.
[Scott, Rodney J.] John Hunter Hosp, Hunter Area Pathol Serv, Newcastle, NSW, Australia.
[Scott, Rodney J.; Ashton, Katie] Univ Newcastle, Sch Biomed Sci & Pharm, Ctr Informat Based Med, Newcastle, NSW 2300, Australia.
[Ashton, Katie] Univ Newcastle, Sch Biomed Sci & Pharm, Discipline Med Genet, Newcastle, NSW 2300, Australia.
[Proietto, Tony; Otton, Geoffrey] Univ Newcastle, Sch Med & Publ Hlth, Newcastle, NSW 2300, Australia.
[Wersaell, Ofra; Mints, Miriam] Karolinska Inst, Karolinska Univ Hosp, Dept Womens & Childrens Hlth, Stockholm, Sweden.
[Tham, Emma; Lindblom, Annika; RENDOCAS] Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.
[Hall, Per; Czene, Kamila] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
[Liu, Jianjun; Li, Jingmei] Genome Inst Singapore, Singapore, Singapore.
[Hopper, John L.; Giles, Graham G.] Univ Melbourne, Melbourne Sch Populat & Global Hlth, Ctr Epidemiol & Biostat, Melbourne, Vic, Australia.
[Southey, Melissa C.] Univ Melbourne, Genet Epidemiol Lab, Dept Pathol, Melbourne, Vic, Australia.
[AOCS] Peter MacCallum Canc Ctr, Melbourne, Vic, Australia.
[Johnson, Nichola] Inst Canc Res, Breakthrough Breast Canc Res Ctr, London SW3 6JB, England.
[Peto, Julian] London Sch Hyg & Trop Med, London WC1, England.
[Burwinkel, Barbara; Marme, Frederik] Heidelberg Univ, Dept Gynecol & Obstet, Heidelberg, Germany.
[Burwinkel, Barbara; Brenner, Hermann; Dieffenbach, Aida K.] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany.
[Marme, Frederik; Brenner, Hermann; Dieffenbach, Aida K.] German Canc Consortium DKTK, Heidelberg, Germany.
[Meindl, Alfons] Tech Univ Munich, Dept Obstet & Gynecol, Div Tumor Genet, D-80290 Munich, Germany.
[Brauch, Hiltrud] Univ Tubingen, Dr Margarete Fischer Bosch Inst Clin Pharmacol St, Tubingen, Germany.
Univ Med Ctr Hamburg Eppendorf, Inst Occupat Med & Maritime Med, Hamburg, Germany.
Johanniter Krankenhaus, Evangel Kliniken Bonn gGmbH, Dept Internal Med, Bonn, Germany.
Univ Bonn, Inst Pathol, Fac Med, Bonn, Germany.
Ruhr Univ Bochum IPA, German Social Accid Insurance, Inst Prevent & Occupat Med, Bochum, Germany.
[GENICA Network] Deutsch Krebsforschungszentrum DKFZ, Mol Genet Breast Canc, Heidelberg, Germany.
[Chang-Claude, Jenny] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany.
[Rudolph, Anja] Univ Clin Hamburg Eppendorf, Dept Canc Epidemiol, Clin Canc Registry, Hamburg, Germany.
[Rudolph, Anja] Univ Clin Hamburg Eppendorf, Inst Med Biometr & Epidemiol, Hamburg, Germany.
[Couch, Fergus J.; Cunningham, Julie M.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA.
[Couch, Fergus J.; Cunningham, Julie M.] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA.
[Giles, Graham G.; Bruinsma, Fiona] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic, Australia.
[Giles, Graham G.] Monash Univ, Dept Epidemiol & Prevent Med, Melbourne, Vic 3004, Australia.
[Fridley, Brooke L.] Univ Kansas, Med Ctr, Dept Biostat, Kansas City, KS 66103 USA.
[Borresen-Dale, Anne-Lise; Kristensen, Vessela N.] Norwegian Radium Hosp, Inst Canc Res, Dept Genet, Oslo, Norway.
[Borresen-Dale, Anne-Lise; Kristensen, Vessela N.] Univ Oslo, Inst Clin Med, KG Jebsen Ctr Breast Canc Res, Fac Med, Oslo, Norway.
[Kristensen, Vessela N.] Akershus Univ Hosp, Dept Clin Mol Oncol, Div Med, Ahus, Norway.
[Cox, Angela] Univ Sheffield, Sheffield Canc Res Ctr, Dept Oncol, Sheffield, S Yorkshire, England.
[Swerdlow, Anthony J.] Inst Canc Res, Div Genet & Epidemiol, London SW3 6JB, England.
[Swerdlow, Anthony J.; Orr, Nicholas] Inst Canc Res, Div Breast Canc Res, London SW3 6JB, England.
[Weber, Rachel Palmieri] Duke Univ, Sch Med, Dept Community & Family Med, Durham, NC USA.
[Chen, Zhihua] Univ S Florida, H Lee Moffitt Canc Ctr, Dept Canc Epidemiol, Div Populat Sci, Tampa, FL 33682 USA.
RP Hopper, JL (reprint author), Univ Calif Davis, Sch Med, Genome Ctr, Davis, CA 95616 USA.
EM lgcarvajal@ucdavis.edu; djt25@medschl.cam.ac.uk
RI Hein, Alexander/F-6999-2010; Fridley, Brooke/D-8315-2015; Li,
Jingmei/I-2904-2012; Dork, Thilo/J-8620-2012; Bowtell,
David/H-1007-2016; Brenner, Hermann/B-4627-2017; salvesen,
Helga/C-1187-2017; Cheng, Timothy/D-8747-2017; Spurdle,
Amanda/A-4978-2011; O'Mara, Tracy/M-7508-2016; Renner,
Stefan/F-1158-2014
OI Dunning, Alison Margaret/0000-0001-6651-7166; Cox,
Angela/0000-0002-5138-1099; Moisse, Matthieu/0000-0001-8880-9311;
Njolstad, Tormund/0000-0003-4024-3819; Giles,
Graham/0000-0003-4946-9099; Hein, Alexander/0000-0003-2601-3398;
Fridley, Brooke/0000-0001-7739-7956; Li, Jingmei/0000-0001-8587-7511;
Bowtell, David/0000-0001-9089-7525; Brenner,
Hermann/0000-0002-6129-1572; salvesen, Helga/0000-0002-4438-8831;
Spurdle, Amanda/0000-0003-1337-7897; Lose, Felicity/0000-0001-8337-3547;
Czene, Kamila/0000-0002-3233-5695; O'Mara, Tracy/0000-0002-5436-3232;
Renner, Stefan/0000-0003-2057-1268
FU NHMRC [1031333]; University of California Davis; V Foundation for Cancer
Research; National Institute On Aging [P30AG043097]; National Cancer
Institute of the National Institutes of Health [K12CA138464]; National
Health and Medical Research Council (NHMRC); Joseph Mitchell Trust;
Cancer Research UK; Oxford Comprehensive Biomedical Research Centre; Dr.
Mildred Scheel Stiftung of the Deutsche Krebshilfe (German Cancer Aid);
European Community [223175 (HEALTH-F2-2009-223175)]; Cancer Research UK
[C1287/A10118, C1287/A 10710, C12292/A11174, C1281/A12014, C5047/A8384,
C5047/A15007, C5047/A10692, C490/A10124, C1287/A12014]; 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); Komen
Foundation for the Cure; Breast Cancer Research Foundation; Ovarian
Cancer Research Fund; NCI [CA 15083]; National Health and Medical
Research Council of Australia [339435]; Cancer Council Queensland
[4196615]; Cancer Council Tasmania [403031, 457636]; National Health and
Medical Research Council [1031333]; Oxford Comprehensive Biomedical
Research Centre [075491/Z/04]; University of Erlangen; Verelst
Foundation for endometrial cancer; National Cancer Institute of United
States Public Health Service [R01 CA122443, P30 CA15083, P50 CA136393,
RO1 CA 092585, R01 CA90899, R01 CA64277]; GAME-ON the NCI Cancer
Post-GWAS Initiative [U19 CA148112]; Fred C and Katherine B Andersen
Foundation; Mayo Foundation; Smith family; Helse Vest Grant; University
of Bergen; Melzer Foundation; Norwegian Cancer Society (Harald Andersens
legat); Research Council of Norway; Haukeland University Hospital;
Stockholm County Council [20110222, 20110483, 20110141, DF 07015];
Karolinska Institutet [20110222, 20110483, 20110141, DF 07015]; Swedish
Labor Market Insurance [100069]; Swedish Cancer Society [11 0439];
Agency for Science, Technology and Research of Singapore (A*STAR); US
National Institute of Health (NIH); Susan G. Komen Breast Cancer
Foundation; Ovarian Cancer Research Fund [PPD/RPCI.07]; UK National
Institute for Health Research Biomedical Research Centres at the
University of Cambridge
FX The authors thank the many individuals who participated in this study
and the numerous institutions and their staff who have supported
recruitment, detailed in full in the Supplementary Notes. Fine-mapping
analysis was supported by NHMRC Project Grant (ID#1031333) to ABS, DFE
and AMD. LGC-C receives funding from the University of California Davis,
The V Foundation for Cancer Research, and The National Institute On
Aging (award number P30AG043097) and The National Cancer Institute
(award number K12CA138464) of the National Institutes of Health. The
content is solely the responsibility of the authors and does not
necessarily represent the official views of the National Institutes of
Health. ABS is supported by the National Health and Medical Research
Council (NHMRC) Fellowship scheme. D. F. E. is a Principal Research
Fellow of Cancer Research UK. A. M. D. is supported by the Joseph
Mitchell Trust. I. T. is supported by Cancer Research UK and the Oxford
Comprehensive Biomedical Research Centre. P. A. F. was partly funded by
the Dr. Mildred Scheel Stiftung of the Deutsche Krebshilfe (German
Cancer Aid). FA is senior clinical researcher for the Research Fund
Flanders (F.W.O.). Funding for the iCOGS infrastructure came from: the
European Community's Seventh Framework Programme under Grant agreement
no 223175 (HEALTH-F2-2009-223175) (COGS), Cancer Research UK
(C1287/A10118, C1287/A 10710, C12292/A11174, C1281/A12014, 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. NCI CA 15083 (Mayo Clinic CCSG) supported the
genotyping carried out by the Genotyping Core laboratory. ANECS
recruitment was supported by Project Grants from the National Health and
Medical Research Council of Australia (ID#339435), The Cancer Council
Queensland (ID#4196615) and Cancer Council Tasmania (ID#403031 and
ID#457636). SEARCH recruitment was funded by a programme Grant from
Cancer Research UK (C490/A10124). Case genotyping was supported by the
National Health and Medical Research Council (ID#1031333). NSECG was
supported principally by Cancer Research UK and by funds from the Oxford
Comprehensive Biomedical Research Centre, with core infrastructure
support to the Wellcome Trust Centre for Human Genetics, Oxford provided
by Grant 075491/Z/04. The Bavarian Endometrial Cancer Study (BECS) was
partly funded by the ELAN fund of the University of Erlangen. The Leuven
Endometrium Study (LES) was supported by the Verelst Foundation for
endometrial cancer. The Mayo Endometrial Cancer Study (MECS) and Mayo
controls (MAY) were supported by Grants from the National Cancer
Institute of United States Public Health Service (R01 CA122443, P30
CA15083, P50 CA136393, and GAME-ON the NCI Cancer Post-GWAS Initiative
U19 CA148112), the Fred C and Katherine B Andersen Foundation, the Mayo
Foundation, and the Ovarian Cancer Research Fund with support of the
Smith family, in memory of Kathryn Sladek Smith. MoMaTEC received
financial support from a Helse Vest Grant, the University of Bergen,
Melzer Foundation, The Norwegian Cancer Society (Harald Andersens
legat), The Research Council of Norway and Haukeland University
Hospital.; The Newcastle Endometrial Cancer Study (NECS) acknowledges
contributions from the University of Newcastle, The NBN Children's
Cancer Research Group, Ms Jennie Thomas and the Hunter Medical Research
Institute. RENDOCAS was supported through the regional agreement on
medical training and clinical research (ALF) between Stockholm County
Council and Karolinska Institutet (numbers: 20110222, 20110483, 20110141
and DF 07015), The Swedish Labor Market Insurance (number 100069) and
The Swedish Cancer Society (number 11 0439). The Cancer Hormone
Replacement Epidemiology in Sweden Study (CAHRES, formerly called The
Singapore and Swedish Breast/Endometrial Cancer Study; 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. The Shanghai
Endometrial Cancer Genetic Study (SECGS) was supported by Grants from
the National Cancer Institute of United States Public Health Service
(RO1 CA 092585 and R01 CA90899, R01 CA64277). The Breast Cancer
Association Consortium (BCAC) is funded by Cancer Research UK
(C1287/A10118, C1287/A12014). The Ovarian Cancer Association Consortium
(OCAC) is supported by a grant from the Ovarian Cancer Research Fund
thanks to donations by the family and friends of Kathryn Sladek Smith
(PPD/RPCI.07), and the UK National Institute for Health Research
Biomedical Research Centres at the University of Cambridge. Additional
funding for individual control groups is detailed in the Supplementary
Text.
NR 63
TC 11
Z9 11
U1 1
U2 10
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0340-6717
EI 1432-1203
J9 HUM GENET
JI Hum. Genet.
PD FEB
PY 2015
VL 134
IS 2
BP 231
EP 245
DI 10.1007/s00439-014-1515-4
PG 15
WC Genetics & Heredity
SC Genetics & Heredity
GA AZ3TM
UT WOS:000348149500010
PM 25487306
ER
PT J
AU Rivera, MM
Soza, A
Jazwinski, A
Mi, LJ
Kleiner, DE
Zhao, XC
Zuber, C
Brust, D
Hsu, E
Simpson, J
Hoofnagle, JH
Heller, T
AF Rivera, Maria M.
Soza, Alejandro
Jazwinski, Alison
Mi, Lijun
Kleiner, David E.
Zhao, Xiongce
Zuber, Charma
Brust, Douglas
Hsu, Emory
Simpson, Jennifer
Hoofnagle, Jay H.
Heller, Theo
TI HIV Through the Looking Glass: Insights Derived From Hepatitis B
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Article
DE co-infection; HBV; HIV; immune
ID VIRUS-INFECTION; HOMOSEXUAL-MEN; CORE ANTIGEN; MICROBIAL TRANSLOCATION;
MORTALITY; PROGRESSION; HEPATOCYTE; PREVALENCE; THERAPY; PATIENT
AB Background:Although higher levels of hepatitis B virus (HBV) replication in HIV-HBV co-infection may relate to liver disease progression, this has not been completely elucidated. We used expression of hepatitis B core antigen (HBcAg) in liver biopsies from HIV-HBV co-infected and HBV mono-infected patients as a marker for HBV replication, and related these findings to clinical and histological parameters.Methods:Data from 244 HBV patients were compared with 34 HIV-HBV patients. Liver biopsies were scored for inflammation, fibrosis, HBcAg, and hepatitis B surface antigen. Univariate and multivariate analyses were performed.Results:HBcAg, but not hepatitis B surface antigen, staining was stronger in HIV co-infected than in HBV mono-infected. Co-infected and HBV mono-infected had similar alanine aminotransferase, inflammatory and fibrosis scores, and hepatitis B e antigen status. HBcAg staining correlated with HIV after correcting for HBV DNA and hepatitis B e antigen. CD4 counts and HIV RNA level did not correlate with intensity of HBcAg staining. HBV DNA levels were higher in HIV co-infected and correlated with HBcAg staining.Conclusions:By looking at HBcAg as a reflection of HBV replication in HIV-HBV co-infected with controlled HIV, our findings suggest that these patients may have subtle immune function defects, which could lead to adverse liver disease outcomes.
C1 [Rivera, Maria M.; Jazwinski, Alison; Mi, Lijun; Zhao, Xiongce; Hsu, Emory; Simpson, Jennifer; Hoofnagle, Jay H.; Heller, Theo] NIDDK, Liver Dis Branch, NIH, Bethesda, MD 20892 USA.
[Soza, Alejandro] Pontificia Univ Catolica Chile, NIH, Bethesda, MD USA.
[Kleiner, David E.] NCI, NIH, Bethesda, MD 20892 USA.
[Zuber, Charma] NIH, Ctr Clin, Bethesda, MD 20892 USA.
[Brust, Douglas] NIAID, NIH, Bethesda, MD 20892 USA.
RP Heller, T (reprint author), NIDDK, Liver Dis Branch, NIH, 10 Ctr Dr MSC 1800,Bldg 10,Room 9B16, Bethesda, MD 20892 USA.
EM theoh@intra.niddk.nih.gov
FU National Institute of Diabetes and Digestive and Kidney Diseases [Z01
DK054514-02 LDB]; National Cancer Institute; Clinical Center, National
Institutes of Health, Bethesda, MD
FX Supported by the intramural research program of the National Institute
of Diabetes and Digestive and Kidney Diseases (Z01 DK054514-02 LDB),
National Cancer Institute, and the Clinical Center, National Institutes
of Health, Bethesda, MD.
NR 21
TC 0
Z9 0
U1 1
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1525-4135
EI 1077-9450
J9 JAIDS-J ACQ IMM DEF
JI JAIDS
PD FEB 1
PY 2015
VL 68
IS 2
BP 123
EP 127
DI 10.1097/QAI.0000000000000415
PG 5
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA AZ8IF
UT WOS:000348458200006
PM 25590267
ER
PT J
AU Kahana, SY
Fernandez, MI
Wilson, PA
Bauermeister, JA
Lee, S
Wilson, CM
Hightow-Weidman, LB
AF Kahana, Shoshana Y.
Fernandez, Maria Isabel
Wilson, Patrick A.
Bauermeister, Jose A.
Lee, Sonia
Wilson, Craig M.
Hightow-Weidman, Lisa B.
TI Rates and Correlates of Antiretroviral Therapy Use and Virologic
Suppression Among Perinatally and Behaviorally HIV-Infected Youth Linked
to Care in the United States
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Article
DE HIV; youth; antiretroviral therapy; viral suppression
ID SEXUALLY-TRANSMITTED INFECTIONS; YOUNG-ADULTS; ACQUIRED HIV; POSITIVE
ADOLESCENTS; DRUG-RESISTANCE; SCREENING-TEST; VIRAL LOAD; HEALTH;
DISPARITIES; ADHERENCE
AB Objective:To measure rates of antiretroviral therapy (ART) use and virologic suppression among perinatally HIV-infected youth (PIY) and behaviorally HIV-infected youth (BIY) linked to care in the United States and examine the effects of demographic, biomedical, and psychosocial factors on those rates.Methods:Between 2009 and 2012, 649 PIY and 1547 BIY in 20 Adolescent Medicine Trials Network for HIV/AIDS Interventions sites completed cross-sectional surveys through audio computer-assisted self-interviews. Viral load data were collected from chart abstraction or blood draw.Results:Overall 82.4% of PIY and 49.1% of BIY reported current ART use. Only 37.0% of PIY and 27.1% of BIY were virologically suppressed. Virologic suppression rates did not vary as a function of time since HIV diagnosis in either group. Consistent HIV care and no current substance abuse were significant correlates of ART use among PIY. These variables and non-African American race were some factors associated with virologic suppression for PIY [odds ratios (ORs) P < 0.05]. Among BIY, older age, heterosexuals, employment, and education were significantly related to ART use (ORs: P < 0.05); suppression was related to ART use 6 months, 90% ART adherence, and consistent HIV care (ORs: P < 0.05). Nearly 75% (n = 498) of nonsuppressed youth reported unprotected sex in the past 3 months.Conclusions:There are continued challenges with successfully treating youth even once diagnosed and linked to HIV care. Strategies targeting barriers to ART access, use, and virologic suppression are needed to optimize the impact of the Treatment as Prevention paradigm among PIY and BIY.
C1 [Kahana, Shoshana Y.] NIDA, Div Epidemiol, Serv & Prevent Res, NIH, Bethesda, MD 20892 USA.
[Fernandez, Maria Isabel] Nova SE Univ, Coll Osteopath Med, Dept Prevent Med, Ft Lauderdale, FL 33314 USA.
[Fernandez, Maria Isabel] Nova SE Univ, Coll Osteopath Med, Dept Publ Hlth Program, Ft Lauderdale, FL 33314 USA.
[Wilson, Patrick A.] Columbia Univ, Mailman Sch Publ Hlth, Dept Sociomed Sci, New York, NY USA.
[Bauermeister, Jose A.] Univ Michigan, Sch Publ Hlth, Dept Hlth Behav & Hlth Educ, Ann Arbor, MI 48109 USA.
[Lee, Sonia] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Maternal Pediat Infect Dis Branch, NIH, Bethesda, MD USA.
[Wilson, Craig M.] Univ Alabama Birmingham, Sch Publ Hlth, Dept Epidemiol, Birmingham, AL 35294 USA.
[Hightow-Weidman, Lisa B.] Univ N Carolina, Div Infect Dis, Dept Med, Chapel Hill, NC USA.
RP Kahana, SY (reprint author), NIDA, Div Epidemiol, Serv & Prevent Res, NIH, Bethesda, MD 20892 USA.
EM kahanas@mail.nih.gov
OI Bauermeister, Jose/0000-0002-9276-2306
FU Adolescent Medicine Trials Network for HIV/AIDS Interventions (ATN) from
the National Institutes of Health through the National Institute of
Child Health and Human Development [U01 HD 040533, U01 HD 040474];
National Institute on Drug Abuse; National Institute on Mental Health
FX Supported by The Adolescent Medicine Trials Network for HIV/AIDS
Interventions (ATN) from the National Institutes of Health [U01 HD
040533 and U01 HD 040474] through the National Institute of Child Health
and Human Development (B. Kapogiannis and S.L.), with supplemental
funding from the National Institutes on Drug Abuse (K. Davenny and
S.Y.K.) and Mental Health (P. Brouwers, S. Allison). S.Y.K. and S.L. are
NIDA and NICHD Program Scientists, respectively, with the ATN.
NR 51
TC 13
Z9 13
U1 2
U2 6
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1525-4135
EI 1077-9450
J9 JAIDS-J ACQ IMM DEF
JI JAIDS
PD FEB 1
PY 2015
VL 68
IS 2
BP 169
EP 177
DI 10.1097/QAI.0000000000000408
PG 9
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA AZ8IF
UT WOS:000348458200013
PM 25590270
ER
PT J
AU Olfson, M
King, M
Schoenbaum, M
AF Olfson, Mark
King, Marissa
Schoenbaum, Michael
TI Benzodiazepine Use in the United States
SO JAMA PSYCHIATRY
LA English
DT Article
ID INAPPROPRIATE MEDICATION USE; ELIMINATION HALF-LIFE; LONG-TERM USE;
OLDER-ADULTS; ANXIETY DISORDERS; PERSISTENT INSOMNIA;
BEHAVIORAL-THERAPY; GENERAL-POPULATION; CONSENSUS PANEL; NATIONAL-SURVEY
AB IMPORTANCE Although concern exists regarding the rate of benzodiazepine use, especially long-term use by older adults, little information is available concerning patterns of benzodiazepine use in the United States.
OBJECTIVE To describe benzodiazepine prescription patterns in the United States focusing on patient age and duration of use.
DESIGN, SETTING, AND PARTICIPANTS A retrospective descriptive analysis of benzodiazepine prescriptions was performed with the 2008 LifeLink LRx Longitudinal Prescription database (IMS Health Inc), which includes approximately 60% of all retail pharmacies in the United States. Denominators were adjusted to generalize estimates to the US population.
MAIN OUTCOMES AND MEASURES The percentage of adults filling 1 or more benzodiazepine prescriptions during the study year by sex and age group (18-35 years, 36-50 years, 51-64 years, and 65-80 years) and among individuals receiving benzodiazepines, the corresponding percentages with long-term (>= 120 days) benzodiazepine use, prescription of a long-acting benzodiazepine, and benzodiazepine prescriptions from a psychiatrist.
RESULTS In 2008, approximately 5.2% of US adults aged 18 to 80 years used benzodiazepines. The percentage who used benzodiazepines increased with age from 2.6% (18-35 years) to 5.4%(36-50 years) to 7.4%(51-64 years) to 8.7%(65-80 years). Benzodiazepine use was nearly twice as prevalent in women as men. The proportion of benzodiazepine use that was long term increased with age from 14.7%(18-35 years) to 31.4% (65-80 years), while the proportion that received a benzodiazepine prescription from a psychiatrist decreased with age from 15.0%(18-35 years) to 5.7%(65-80 years). In all age groups, roughly one-quarter of individuals receiving benzodiazepine involved long-acting benzodiazepine use.
CONCLUSIONS AND RELEVANCE Despite cautions concerning risks associated with long-term benzodiazepine use, especially in older patients, long-term benzodiazepine use remains common in this age group. More vigorous clinical interventions supporting judicious benzodiazepine use may be needed to decrease rates of long-term benzodiazepine use in older adults.
C1 [Olfson, Mark] Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY 10032 USA.
[Olfson, Mark] New York State Psychiat Inst & Hosp, New York, NY 10032 USA.
[King, Marissa] Yale Univ, Sch Management, New Haven, CT USA.
[Schoenbaum, Michael] NIMH, Off Director, NIH, Bethesda, MD 20892 USA.
RP Olfson, M (reprint author), Columbia Univ, Coll Phys & Surg, New York State Psychiat Inst, 1051 Riverside Dr, New York, NY 10032 USA.
EM mo49@.columbia.edu
FU National Institutes of Health; Agency for Healthcare Research and
Quality [U19HSO2112]; New York State Psychiatric Institute
FX This research was funded by contracts from the National Institutes of
Health to Yale University (King) and Columbia University (Olfson), grant
U19HSO2112 from the Agency for Healthcare Research and Quality (Olfson),
and the New York State Psychiatric Institute (Olfson).
NR 79
TC 67
Z9 67
U1 4
U2 25
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 2168-622X
EI 2168-6238
J9 JAMA PSYCHIAT
JI JAMA Psychiatry
PD FEB
PY 2015
VL 72
IS 2
BP 136
EP 142
DI 10.1001/jamapsychiatry.2014.1763
PG 7
WC Psychiatry
SC Psychiatry
GA CB2JH
UT WOS:000349452800009
PM 25517224
ER
PT J
AU Fernandez-Boyanapalli, RF
Frasch, SC
Thomas, SM
Malcolm, KC
Nicks, M
Harbeck, RJ
Jakubzick, CV
Nemenoff, R
Henson, PM
Holland, SM
Bratton, DL
AF Fernandez-Boyanapalli, Ruby F.
Frasch, S. Courtney
Thomas, Stacey M.
Malcolm, Kenneth C.
Nicks, Michael
Harbeck, Ronald J.
Jakubzick, Claudia V.
Nemenoff, Raphael
Henson, Peter M.
Holland, Steven M.
Bratton, Donna L.
TI Pioglitazone restores phagocyte mitochondrial oxidants and bactericidal
capacity in chronic granulomatous disease
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Article
DE Chronic granulomatous disease; phagocytes; mitochondria; oxidants;
thioglitazones
ID ACTIVATED-RECEPTOR-GAMMA; REACTIVE OXYGEN; PPAR-GAMMA; NADPH OXIDASE;
SUPEROXIDE-PRODUCTION; INSULIN-RESISTANCE; HUMAN NEUTROPHILS;
CELL-DEATH; INFLAMMATION; MACROPHAGES
AB Background: Deficient production of reactive oxygen species (ROS) by the phagocyte nicotinamide adenine dinucleotide (NADPH) oxidase in patients with chronic granulomatous disease (CGD) results in susceptibility to certain pathogens secondary to impaired oxidative killing and mobilization of other phagocyte defenses. Peroxisome proliferator-activated receptor (PPAR) gamma agonists, including pioglitazone, approved for type 2 diabetes therapy alter cellular metabolism and can heighten ROS production. It was hypothesized that pioglitazone treatment of gp91(phox-/-) mice, a murine model of human CGD, would enhance phagocyte oxidant production and killing of Staphylococcus aureus, a significant pathogen in patients with this disorder.
Objectives: We sought to determine whether pioglitazone treatment of gp91(phox-/-) mice enhanced phagocyte oxidant production and host defense.
Methods: Wild-type and gp91(phox-/-) mice were treated with the PPAR gamma agonist pioglitazone, and phagocyte ROS and killing of Staphylococcus aureus were investigated.
Results: As demonstrated by 3 different ROS-sensing probes, short-term treatment of gp91(phox-/-) mice with pioglitazone enhanced stimulated ROS production in neutrophils and monocytes from blood and neutrophils and inflammatory macrophages recruited to tissues. Mitochondria were identified as the source of ROS. Findings were replicated in human monocytes from patients with CGD after ex vivo pioglitazone treatment. Importantly, although mitochondrial (mt) ROS were deficient in gp91(phox-/-) phagocytes, their restoration with treatment significantly enabled killing of Staphylococcus aureus both ex vivo and in vivo.
Conclusions: Together, the data support the hypothesis that signaling from the NADPH oxidase under normal circumstances governs phagocyte mtROS production and that such signaling is lacking in the absence of a functioning phagocyte oxidase. PPAR gamma agonism appears to bypass the need for the NADPH oxidase for enhanced mtROS production and partially restores host defense in CGD.
C1 [Fernandez-Boyanapalli, Ruby F.; Frasch, S. Courtney; Thomas, Stacey M.; Nicks, Michael; Harbeck, Ronald J.; Jakubzick, Claudia V.; Henson, Peter M.; Bratton, Donna L.] Natl Jewish Med & Res Ctr, Dept Pediat, Denver, CO 80206 USA.
[Malcolm, Kenneth C.; Harbeck, Ronald J.; Henson, Peter M.] Natl Jewish Med & Res Ctr, Dept Med, Denver, CO USA.
[Harbeck, Ronald J.; Henson, Peter M.] Natl Jewish Med & Res Ctr, Dept Immunol, Denver, CO USA.
[Nemenoff, Raphael] Univ Denver, Dept Med, Div Renal Dis & Hypertens, Denver, CO 80208 USA.
[Holland, Steven M.] NIAID, Labs Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
RP Bratton, DL (reprint author), Natl Jewish Med & Res Ctr, Dept Pediat, Rm A540,1400 Jackson St, Denver, CO 80206 USA.
EM brattond@njhealth.org
OI Thomas, Stacey/0000-0002-5666-4311
FU National Institutes of Health [AI058228, AI110408, HL34303]; Chronic
Granulomatous Disorder Society (United Kingdom) [J4G/10/03]
FX This investigation was entirely funded by National Institutes of Health
grants AI058228, AI110408, and HL34303 and the Chronic Granulomatous
Disorder Society (United Kingdom, J4G/10/03).
NR 69
TC 5
Z9 5
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 FEB
PY 2015
VL 135
IS 2
BP 517
EP U323
DI 10.1016/j.jaci.2014.10.034
PG 23
WC Allergy; Immunology
SC Allergy; Immunology
GA CB1FL
UT WOS:000349372300026
PM 25498313
ER
PT J
AU Czifra, G
Szollosi, A
Nagy, Z
Boros, M
Juhasz, I
Kiss, A
Erdodi, F
Szabo, T
Kovacs, I
Torok, M
Kovacs, L
Blumberg, PM
Biro, T
AF Czifra, Gabriella
Szoellosi, Attila
Nagy, Zsuzsanna
Boros, Miklos
Juhasz, Istvan
Kiss, Andrea
Erdodi, Ferenc
Szabo, Tamas
Kovacs, Ilona
Toeroek, Miklos
Kovacs, Laszlo
Blumberg, Peter M.
Biro, Tamas
TI Protein kinase C delta promotes proliferation and induces malignant
transformation in skeletal muscle
SO JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
LA English
DT Article
DE Skeletal muscle; C2C12 myoblasts; rhabdomyosarcoma; protein kinase C;
nPKC delta; PKC isoenzymes; recombinant overexpression; proliferation;
differentiation; tumourigenesis
ID GROWTH-FACTOR; IGF-I; RHABDOMYOSARCOMA CELLS; GLUCOSE-TRANSPORT;
SATELLITE CELLS; NIH 3T3-CELLS; DIFFERENTIATION; EXPRESSION; MYOBLASTS;
ISOFORMS
AB In this paper, we investigated the isoform-specific roles of certain protein kinase C (PKC) isoforms in the regulation of skeletal muscle growth. Here, we provide the first intriguing functional evidence that nPKC (originally described as an inhibitor of proliferation in various cells types) is a key player in promoting both in vitro and in vivo skeletal muscle growth. Recombinant overexpression of a constitutively active nPKC in C2C12 myoblast increased proliferation and inhibited differentiation. Conversely, overexpression of kinase-negative mutant of nPKC (DN-nPKC) markedly inhibited cell growth. Moreover, overexpression of nPKC also stimulated in vivo tumour growth and induced malignant transformation in immunodeficient (SCID) mice whereas that of DN-nPKC suppressed tumour formation. The role of nPKC in the formation of rhabdomyosarcoma was also investigated where recombinant overexpression of nPKC in human rhabdomyosarcoma RD cells also increased cell proliferation and enhanced tumour formation in mouse xenografts. The other isoforms investigated (PKC, , epsilon) exerted only minor (mostly growth-inhibitory) effects in skeletal muscle cells. Collectively, our data introduce nPKC as a novel growth-promoting molecule in skeletal muscles and invite further trials to exploit its therapeutic potential in the treatment of skeletal muscle malignancies.
C1 [Czifra, Gabriella; Szoellosi, Attila; Nagy, Zsuzsanna; Boros, Miklos; Kovacs, Laszlo; Biro, Tamas] Univ Debrecen, Dept Physiol, DE MTA Lendulet Cellular Physiol Res Grp, Med Fac,Res Ctr Mol Med, H-4032 Debrecen, Hungary.
[Juhasz, Istvan] Univ Debrecen, Fac Med, Dept Dermatol, Res Ctr Mol Med, H-4012 Debrecen, Hungary.
[Kiss, Andrea; Erdodi, Ferenc] Univ Debrecen, Dept Med Chem, Fac Med, Res Ctr Mol Med, H-4032 Debrecen, Hungary.
[Szabo, Tamas] Univ Debrecen, Dept Pediat, Fac Med, Res Ctr Mol Med, H-4032 Debrecen, Hungary.
[Kovacs, Ilona; Toeroek, Miklos] Gyula Kenezy Hosp, Dept Pathol, Debrecen, Hungary.
[Blumberg, Peter M.] NCI, Lab Canc Biol & Genet, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Czifra, G (reprint author), Univ Debrecen, Dept Physiol, Nagyerdei Krt 98 POB 22, H-4032 Debrecen, Hungary.
EM czifrag@gmail.com
FU Hungarian research grants "Lendulet" [LP2011-003/2014,
TAMOP-4.2.2.A-11/1/KONV-2012-0025, TAMOP-4.2.2.A-11/1/KONV-2012-0045];
University of Debrecen [RH/885/2013]; [TAMOP-4.2.2./B-10/1-2010-0024]
FX This work was supported by Hungarian research grants "Lendulet"
LP2011-003/2014, TAMOP-4.2.2.A-11/1/KONV-2012-0025 and
TAMOP-4.2.2.A-11/1/KONV-2012-0045 as well as by the University of
Debrecen (RH/885/2013). ZN is a recipient of the
TAMOP-4.2.2./B-10/1-2010-0024 Predoctoral Research Scholarship. The
technical assistance of Ms. Ibolya Varga and Janos Vincze is gratefully
appreciated.
NR 51
TC 0
Z9 1
U1 0
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1582-4934
J9 J CELL MOL MED
JI J. Cell. Mol. Med.
PD FEB
PY 2015
VL 19
IS 2
BP 396
EP 407
DI 10.1111/jcmm.12452
PG 12
WC Cell Biology; Medicine, Research & Experimental
SC Cell Biology; Research & Experimental Medicine
GA CA7NQ
UT WOS:000349104500011
PM 25283340
ER
PT J
AU Chang, KK
Frankovich, J
Cooperstock, M
Cunningham, MW
Latimer, ME
Murphy, TK
Pasternack, M
Thienemann, M
Williams, K
Walter, J
Swedo, SE
AF Chang, Kiki
Frankovich, Jennifer
Cooperstock, Michael
Cunningham, Madeleine W.
Latimer, M. Elizabeth
Murphy, Tanya K.
Pasternack, Mark
Thienemann, Margo
Williams, Kyle
Walter, Jolan
Swedo, Susan E.
CA PANS Collaborative Consortium
TI Clinical Evaluation of Youth with Pediatric Acute-Onset Neuropsychiatric
Syndrome (PANS): Recommendations from the 2013 PANS Consensus Conference
SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY
LA English
DT Article
ID MYCOPLASMA-PNEUMONIAE INFECTION; OBSESSIVE-COMPULSIVE DISORDER;
STREPTOCOCCAL INFECTIONS; SYDENHAMS CHOREA; ANTINUCLEAR ANTIBODIES;
TOURETTES-SYNDROME; CHILDREN; DISEASE; PANDAS; PATHOGENESIS
AB On May 23 and 24, 2013, the First PANS Consensus Conference was convened at Stanford University, calling together a geographically diverse group of clinicians and researchers from complementary fields of pediatrics: General and developmental pediatrics, infectious diseases, immunology, rheumatology, neurology, and child psychiatry. Participants were academicians with clinical and research interests in pediatric autoimmune neuropsychiatric disorder associated with streptococcus (PANDAS) in youth, and the larger category of pediatric acute-onset neuropsychiatric syndrome (PANS). The goals were to clarify the diagnostic boundaries of PANS, to develop systematic strategies for evaluation of suspected PANS cases, and to set forth the most urgently needed studies in this field. Presented here is a consensus statement proposing recommendations for the diagnostic evaluation of youth presenting with PANS.
C1 [Chang, Kiki] Stanford Univ, Sch Med, Pediat Bipolar Disorders Program, Stanford, CA 94305 USA.
[Frankovich, Jennifer] Stanford Univ, Sch Med, Stanford, CA 94305 USA.
[Cooperstock, Michael] Univ Missouri, Sch Med, Div Infect Dis & Rheumatol, Columbia, MO USA.
[Cunningham, Madeleine W.] Univ Oklahoma, Coll Med, Norman, OK 73019 USA.
[Latimer, M. Elizabeth] Latimer Neurol Ctr, Bethesda, MD USA.
[Murphy, Tanya K.] Univ S Florida, St Petersburg, FL 33701 USA.
[Pasternack, Mark] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Thienemann, Margo] Stanford Univ, Sch Med, Adjunct Clin Fac, Stanford, CA 94305 USA.
[Williams, Kyle] Massachusetts Gen Hosp, Behav & Immunol Clin OCD, Boston, MA 02114 USA.
[Williams, Kyle] Massachusetts Gen Hosp, Related Disorders Program, Boston, MA 02114 USA.
[Walter, Jolan] Massachusetts Gen Hosp, Pediat Immunodeficiency Program, Boston, MA 02114 USA.
[Swedo, Susan E.] NIMH, Pediat & Dev Neurosci Branch, Rockville, MD 20857 USA.
RP Chang, KK (reprint author), Stanford Univ, Sch Med, Div Child & Adolescent Psychiat, 401 Quarry Rd, Stanford, CA 94305 USA.
EM kchang88@stanford.edu
RI Murphy, Tanya/J-7079-2013
FU GlaxoSmithKline; Merck
FX Dr. Chang is an unpaid consultant for GlaxoSmithKline, Lilly, and
Bristol-Myers Squibb. He is on the DSMB for Sunovion. In the past two
years he has received research support from GlaxoSmithKline and Merck.
Dr. Walter is on the Advisory Board of Baxter regarding IGHy, a new
formulation of subcutaneous immunoglobulin.
NR 48
TC 13
Z9 13
U1 6
U2 16
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1044-5463
EI 1557-8992
J9 J CHILD ADOL PSYCHOP
JI J. Child Adolesc. Psychopharmacol.
PD FEB 1
PY 2015
VL 25
IS 1
SI SI
BP 3
EP 13
DI 10.1089/cap.2014.0084
PG 11
WC Pediatrics; Pharmacology & Pharmacy; Psychiatry
SC Pediatrics; Pharmacology & Pharmacy; Psychiatry
GA CB4RF
UT WOS:000349614900002
PM 25325534
ER
PT J
AU Swedo, SE
Seidlitz, J
Kovacevic, M
Latimer, ME
Hommer, R
Lougee, L
Grant, P
AF Swedo, Susan E.
Seidlitz, Jakob
Kovacevic, Miro
Latimer, M. Elizabeth
Hommer, Rebecca
Lougee, Lorraine
Grant, Paul
TI Clinical Presentation of Pediatric Autoimmune Neuropsychiatric Disorders
Associated with Streptococcal infections in Research and Community
Settings
SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY
LA English
DT Article
ID OBSESSIVE-COMPULSIVE DISORDER; TOURETTES-SYNDROME; SYDENHAMS CHOREA;
PLASMA-EXCHANGE; CHILDHOOD; PANDAS; EXACERBATIONS; PROPHYLAXIS;
PENICILLIN; TICS
AB Background: The first cases of pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) were described>15 years ago. Since that time, the literature has been divided between studies that successfully demonstrate an etiologic relationship between Group A streptococcal (GAS) infections and childhood-onset obsessive-compulsive disorder (OCD), and those that fail to find an association. One possible explanation for the conflicting reports is that the diagnostic criteria proposed for PANDAS are not specific enough to describe a unique and homogeneous cohort of patients. To evaluate the validity of the PANDAS criteria, we compared clinical characteristics of PANDAS patients identified in two community practices with a sample of children meeting full research criteria for PANDAS.
Methods: A systematic review of clinical records was used to identify the presence or absence of selected symptoms in children evaluated for PANDAS by physicians in Hinsdale, Illinois (n=52) and Bethesda, Maryland (n=40). Results were compared against data from participants in National Institute of Mental Health (NIMH) research investigations of PANDAS (n=48).
Results: As described in the original PANDAS cohort, males outnumbered females (95:45) by similar to 2:1, and symptoms began in early childhood (7.3 +/- 2.7 years). Clinical presentations were remarkably similar across sites, with all children reporting acute onset of OCD symptoms and multiple comorbidities, including separation anxiety (86-92%), school issues (75-81%), sleep disruptions (71%), tics (60-65%), urinary symptoms (42-81%), and others. Twenty of the community cases (22%) failed to meet PANDAS criteria because of an absence of documentation of GAS infections.
Conclusions: The diagnostic criteria for PANDAS can be used by clinicians to accurately identify patients with common clinical features and shared etiology of symptoms. Although difficulties in documenting an association between GAS infection and symptom onset/exacerbations may preclude a diagnosis of PANDAS in some children with acute-onset OCD, they do appear to meet criteria for pediatric acute-onset neuropsychiatric syndrome (PANS).
C1 [Swedo, Susan E.; Seidlitz, Jakob; Hommer, Rebecca; Lougee, Lorraine; Grant, Paul] NIMH, Pediat & Dev Neurosci Branch, Bethesda, MD 20892 USA.
[Kovacevic, Miro] Loyola Univ, Sch Med, Dept Pediat, Hinsdale, IL USA.
[Latimer, M. Elizabeth] Georgetown Univ, Sch Med, Washington, DC USA.
RP Swedo, SE (reprint author), NIMH, Pediat & Dev Neurosci Branch, 10 Ctr Dr,MSC 1255, Bethesda, MD 20892 USA.
EM swedos@mail.nih.gov
FU Intramural Research Program of the NIMH [11-M-0058 (NCT01281969),
13-M-0028 (NCT01778504)]
FX Funding: The research was supported (in part) by the Intramural Research
Program of the NIMH, including protocols 11-M-0058 (NCT01281969) and
13-M-0028 (NCT01778504).
NR 20
TC 5
Z9 5
U1 5
U2 17
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1044-5463
EI 1557-8992
J9 J CHILD ADOL PSYCHOP
JI J. Child Adolesc. Psychopharmacol.
PD FEB 1
PY 2015
VL 25
IS 1
SI SI
BP 26
EP 30
DI 10.1089/cap.2014.0073
PG 5
WC Pediatrics; Pharmacology & Pharmacy; Psychiatry
SC Pediatrics; Pharmacology & Pharmacy; Psychiatry
GA CB4RF
UT WOS:000349614900004
PM 25695941
ER
PT J
AU Toufexis, MD
Hommer, R
Gerardi, DM
Grant, P
Rothschild, L
D'Souza, P
Williams, K
Leckman, J
Swedo, SE
Murphy, TK
AF Toufexis, Megan D.
Hommer, Rebecca
Gerardi, Diana M.
Grant, Paul
Rothschild, Leah
D'Souza, Precilla
Williams, Kyle
Leckman, James
Swedo, Susan E.
Murphy, Tanya K.
TI Disordered Eating and Food Restrictions in Children with PANDAS/PANS
SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY
LA English
DT Article
ID OBSESSIVE-COMPULSIVE DISORDER; MYCOPLASMA-PNEUMONIAE INFECTION;
ANOREXIA-NERVOSA; NEUROPSYCHIATRIC DISORDERS; STREPTOCOCCAL INFECTIONS;
CLINICAL DESCRIPTION; TOURETTES-SYNDROME; BULIMIA-NERVOSA; ADOLESCENTS;
CHILDHOOD
AB Objective: Sudden onset clinically significant eating restrictions are a defining feature of the clinical presentation of some of the cases of pediatric acute-onset neuropsychiatric syndrome (PANS). Restrictions in food intake are typically fueled by contamination fears; fears of choking, vomiting, or swallowing; and/or sensory issues, such as texture, taste, or olfactory concerns. However, body image distortions may also be present. We investigate the clinical presentation of PANS disordered eating and compare it with that of other eating disorders.
Methods: We describe 29 patients who met diagnostic criteria for PANS. Most also exhibited evidence that the symptoms might be sequelae of infections with Group A streptococcal bacteria (the pediatric autoimmune neuropsychiatric disorder associated with streptococcal infections [PANDAS] subgroup of PANS).
Results: The clinical presentations are remarkable for a male predominance (2:1 M:F), young age of the affected children (mean=9 years; range 5-12 years), acuity of symptom onset, and comorbid neuropsychiatric symptoms.
Conclusions: The food refusal associated with PANS is compared with symptoms listed for the new Diagnostic and Statistical Manual of Mental Disorders, 5th ed. (DSM-V) diagnosis of avoidant/restrictive food intake disorder (ARFID). Treatment implications are discussed, as well as directions for further research.
C1 [Toufexis, Megan D.; Gerardi, Diana M.; Murphy, Tanya K.] Univ S Florida, Dept Pediat, Rothman Ctr, Div Pediat Neuropsychiat, St Petersburg, FL 33701 USA.
[Hommer, Rebecca; Grant, Paul; Rothschild, Leah; D'Souza, Precilla; Swedo, Susan E.] NIMH, Pediat & Dev Neurosci Branch, Bethesda, MD 20892 USA.
[Williams, Kyle] Massachusetts Gen Hosp, Pediat Neuropsychiat & Immunol Clin, Boston, MA 02114 USA.
[Williams, Kyle] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA.
[Leckman, James] Yale Univ, Sch Med, Ctr Child Study, New Haven, CT 06510 USA.
[Murphy, Tanya K.] Univ S Florida, Dept Psychiat, Tampa, FL USA.
RP Toufexis, MD (reprint author), USF Dept Pediat, Rothman Ctr Pediat Neuropsychiat, 880 6th St South,Suite 460,Box 7523, St Petersburg, FL 33701 USA.
EM mtoufexi@health.usf.edu
RI Murphy, Tanya/J-7079-2013
FU Intramural Research Program of the NIMH [11-M-0058 (NCT01281969)]
FX This research was supported (in part) by the Intramural Research Program
of the NIMH, including protocol 11-M-0058 (NCT01281969).
NR 50
TC 3
Z9 3
U1 3
U2 13
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1044-5463
EI 1557-8992
J9 J CHILD ADOL PSYCHOP
JI J. Child Adolesc. Psychopharmacol.
PD FEB 1
PY 2015
VL 25
IS 1
SI SI
BP 48
EP 56
DI 10.1089/cap.2014.0063
PG 9
WC Pediatrics; Pharmacology & Pharmacy; Psychiatry
SC Pediatrics; Pharmacology & Pharmacy; Psychiatry
GA CB4RF
UT WOS:000349614900007
PM 25329522
ER
PT J
AU Kovacevic, M
Grant, P
Swedo, SE
AF Kovacevic, Miro
Grant, Paul
Swedo, Susan E.
TI Use of Intravenous Immunoglobulin in the Treatment of Twelve Youths with
Pediatric Autoimmune Neuropsychiatric Disorders Associated with
Streptococcal infections
SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY
LA English
DT Article
ID OBSESSIVE-COMPULSIVE DISORDER; PLASMA-EXCHANGE; SYDENHAM CHOREA;
CHILDHOOD; PANDAS
AB This is a case series describing 12 youths treated with intravenous immunoglobulin (IVIG) for pediatric autoimmune neuropsychiatric disorder associated with streptococcal infection (PANDAS). Although it is a clinically based series, the case reports provide new information about the short-term benefits of IVIG therapy, and are the first descriptions of long-term outcome for PANDAS patients.
C1 [Kovacevic, Miro] Loyola Univ, Sch Med, Maywood, IL 60153 USA.
[Grant, Paul; Swedo, Susan E.] NIMH, PDN Branch, Bethesda, MD 20892 USA.
RP Swedo, SE (reprint author), NIMH, PDN Branch, 10 Ctr Dr,MSC 1255, Bethesda, MD 20892 USA.
EM swedos@mail.nih.gov
NR 15
TC 4
Z9 4
U1 0
U2 2
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1044-5463
EI 1557-8992
J9 J CHILD ADOL PSYCHOP
JI J. Child Adolesc. Psychopharmacol.
PD FEB 1
PY 2015
VL 25
IS 1
SI SI
BP 65
EP 69
DI 10.1089/cap.2014.0067
PG 5
WC Pediatrics; Pharmacology & Pharmacy; Psychiatry
SC Pediatrics; Pharmacology & Pharmacy; Psychiatry
GA CB4RF
UT WOS:000349614900009
PM 25658609
ER
PT J
AU Latimer, ME
L'Etoile, N
Seidlitz, J
Swedo, SE
AF Latimer, M. Elizabeth
L'Etoile, Nathan
Seidlitz, Jakob
Swedo, Susan E.
TI Therapeutic Plasma Apheresis as a Treatment for 35 Severely Ill Children
and Adolescents with Pediatric Autoimmune Neuropsychiatric Disorders
Associated with Streptococcal Infections
SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY
LA English
DT Article
ID OBSESSIVE-COMPULSIVE DISORDER; SYDENHAMS CHOREA; INTRAVENOUS
IMMUNOGLOBULIN; CHILDHOOD; EXCHANGE; PANDAS; PLASMAPHERESIS; MODEL
AB Background: Because of its reported similarities to Sydenham chorea, therapeutic plasma apheresis (TPA) has been proposed as a potential treatment of pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS). To date, support for the use of TPA has been limited to a few anecdotal reports and a small placebo-controlled trial demonstrating dramatic symptom improvements at 1 month and 1 year follow-up. To evaluate the safety and efficacy of TPA further, we undertook a retrospective review of all PANDAS patients treated with TPA at Georgetown University Hospital between August 2009 and October 2013.
Methods: Forty patients were identified, and sufficient information was available from medical records and telephone interview for 35 cases (88%). All 35 (23 boys; 12 girls) met diagnostic criteria for PANDAS (Swedo et al. 1998) and had severe symptoms. The TPA procedures were performed at Georgetown University Hospital using a protocol that processes a total of 4.5 blood volumes over 3-5 days (three treatments of 1.5 volumes each). Overall symptom improvements at 6 months post-TPA and long-term follow-up were estimated by parents, who also rated changes in individual symptoms to provide information about patterns of improvement.
Results: All patients were reported to have received at least some benefit from TPA, with average improvement of 65% at 6 months post-TPA and 78% at longer-term follow-up. A decrease in the number of reported symptoms also occurred, with particular improvements in obsessive-compulsive disorder (OCD), anxiety, tics, and somatic symptoms, including dysgraphia, sleep difficulties, and urinary urgency or frequency. Contrary to expectations, preceding duration of illness was not correlated with degree of improvement following TPA, suggesting that acuity of illness is not a factor affecting response. Only two adverse events were reported: both involved reopening of the site where the central line had been placed and resolved immediately following application of pressure and re-dressing of the puncture site.
Conclusions: Therapeutic plasma apheresis is an invasive medical intervention that should be reserved for treatment of children and adolescents who are severely affected by PANDAS. In such patients, it appears to be a safe, well-tolerated, and beneficial treatment option.
C1 [Latimer, M. Elizabeth] Georgetown Univ, Sch Med, Washington, DC USA.
[Seidlitz, Jakob; Swedo, Susan E.] NIMH, Pediat & Dev Neurosci Branch, Bethesda, MD 20892 USA.
RP Swedo, SE (reprint author), NIMH, Pediat & Dev Neurosci Branch, 10 Ctr Dr,MSC 1255, Bethesda, MD 20892 USA.
EM swedos@mail.nih.gov
NR 23
TC 4
Z9 4
U1 1
U2 5
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1044-5463
EI 1557-8992
J9 J CHILD ADOL PSYCHOP
JI J. Child Adolesc. Psychopharmacol.
PD FEB 1
PY 2015
VL 25
IS 1
SI SI
BP 70
EP 75
DI 10.1089/cap.2014.0080
PG 6
WC Pediatrics; Pharmacology & Pharmacy; Psychiatry
SC Pediatrics; Pharmacology & Pharmacy; Psychiatry
GA CB4RF
UT WOS:000349614900010
PM 25658452
ER
PT J
AU Wiener, L
Viola, A
Wilfond, BS
Wendler, D
Grady, C
AF Wiener, Lori
Viola, Adrienne
Wilfond, Benjamin S.
Wendler, David
Grady, Christine
TI Contrasting Views of Risk Perception and Influence of Financial
Compensation Between Adolescent Research Participants and Their Parents
SO JOURNAL OF EMPIRICAL RESEARCH ON HUMAN RESEARCH ETHICS
LA English
DT Article
DE teens; payment; decision-making; health status; assent; medical;
psychiatric
ID MEDICAL DECISION-MAKING; BIOMEDICAL-RESEARCH; CLINICAL-TRIALS; CHILDREN;
CONSENT; PAYMENT; PERSPECTIVES; ATTITUDES; BENEFITS; ASSENT
AB U.S. regulations governing pediatric research do not specify the assent process. To identify best practices, it is important to examine parents' and adolescents' views. The present study focuses on parents' and adolescents' views regarding possible research risks and the influence of financial compensation on their willingness to accept research procedures. Interviews were conducted with 177 adolescents participating in clinical research for a medical or psychiatric illness, or as healthy volunteers, and a parent. Significant discordance was found between how bothered the teen would feel from research-related side effects and procedures compared with parental report. Most teens were willing to accept non-beneficial procedures without compensation. Payment had significantly greater influence on healthy volunteers and their parents compared with those with a medical or psychiatric illness. Discordance between adolescent and parental views about risks recommends obtaining direct input from adolescents during the assent process. Modest payments should not raise concerns of undue inducement, especially in teens with pre-existing conditions.
C1 [Wiener, Lori; Viola, Adrienne] NCI, Bethesda, MD 20892 USA.
[Viola, Adrienne] Yale Univ, New Haven, CT USA.
[Wilfond, Benjamin S.] Seattle Childrens Res Inst, Seattle, WA USA.
[Wendler, David; Grady, Christine] NIH, Unit Vulnerable Populat, Ctr Clin, Dept Bioeth, Bethesda, MD 20892 USA.
[Grady, Christine] NIH, Dept Bioeth, Ctr Clin, Bethesda, MD 20892 USA.
RP Grady, C (reprint author), NIH, Dept Bioeth, Ctr Clin, 10 Ctr Dr, Bethesda, MD 20892 USA.
EM cgrady@mail.nih.gov
FU Intramural Program of the National Cancer Institute, Center for Cancer
Research; National Institutes of Health (NIH) Clinical Center; NIH
Program Evaluation Funds
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 in part by the Intramural Program of the National Cancer
Institute, Center for Cancer Research, the National Institutes of Health
(NIH) Clinical Center, and the NIH Program Evaluation Funds. This
funding supported the design and conduct of the study; the collection,
management, analysis, and interpretation of the data; preparation,
review, and approval of the manuscript.
NR 35
TC 0
Z9 0
U1 2
U2 4
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1556-2646
EI 1556-2654
J9 J EMPIR RES HUM RES
JI J. Empir. Res. Hum. Res. Ethics
PD FEB
PY 2015
VL 10
IS 1
BP 49
EP 58
DI 10.1177/1556264614563249
PG 10
WC Ethics; Medical Ethics
SC Social Sciences - Other Topics; Medical Ethics
GA CB4TH
UT WOS:000349620600006
PM 25742666
ER
PT J
AU Narayan, V
Ravindra, KC
Liao, C
Kaushal, N
Carlson, BA
Prabhu, KS
AF Narayan, Vivek
Ravindra, Kodihalli C.
Liao, Chang
Kaushal, Naveen
Carlson, Bradley A.
Prabhu, K. Sandeep
TI Epigenetic regulation of inflammatory gene expression in macrophages by
selenium
SO JOURNAL OF NUTRITIONAL BIOCHEMISTRY
LA English
DT Article
DE Selenium; p300; Epigenetic regulation; Inflammatory gene expression;
Cyclopentenone prostaglandins; Selenoproteins
ID PROSTATE-CANCER CELLS; KETO ACID METABOLITES; FACTOR-KAPPA-B; HISTONE
ACETYLTRANSFERASE; TRANSCRIPTIONAL ACTIVITY; ORGANOSELENIUM COMPOUNDS;
UP-REGULATION; ACETYLATION; ACTIVATION; P300
AB Acetylation of histone and non-histone proteins by histone acetyltransferases plays a pivotal role in the expression of proinflammatory genes. Given the importance of dietary selenium in mitigating inflammation, we hypothesized that selenium supplementation may regulate inflammatory gene expression at the epigenetic level. The effect of selenium towards histone acetylation was examined in both in vitro and in vivo models of inflammation by chromatin immunoprecipitation assays and immunoblotting. Our results indicated that selenium supplementation, as selenite, decreased acetylation of histone H4 at K12 and K16 in COX-2 and TNF alpha promoters, and of the p65 subunit of the redox sensitive transcription factor NF kappa B in primary and immortalized macrophages. On the other hand, selenomethionine had a much weaker effect. Selenite treatment of HIV-1-infected human monocytes also significantly decreased the acetylation of H4 at K12 and K16 on the HIV-1 promoter, supporting the down-regulation of proviral expression by selenium. A similar decrease in histone acetylation was also seen in the colonic extracts of mice treated with dextran sodium sulfate that correlated well with the levels of selenium in the diet. Bone-marrow-derived macrophages from Trsp(fl/fl)Cre(LysM) mice that lack expression of selenoproteins in macrophages confirmed the important role of selenoproteins in the inhibition of histone H4 acetylation. Our studies suggest that the ability of selenoproteins to skew the metabolism of arachidonic acid contributes, in part, to their ability to inhibit histone acetylation. In summary, our studies suggest a new role for selenoproteins in the epigenetic modulation of proinflammatory genes. (C) 2015 Elsevier Inc. All rights reserved.
C1 [Narayan, Vivek; Ravindra, Kodihalli C.; Liao, Chang; Kaushal, Naveen; Prabhu, K. Sandeep] Penn State Univ, Ctr Mol Immunol & Infect Dis, Dept Vet & Biomed Sci, University Pk, PA 16802 USA.
[Carlson, Bradley A.] NCI, Mol Biol Selenium Sect, Mouse Canc Genet Program, NIH, Bethesda, MD 20892 USA.
RP Prabhu, KS (reprint author), Penn State Univ, Ctr Mol Toxicol & Carcinogenesis, Dept Vet & Biomed Sci, University Pk, PA 16802 USA.
EM ksprabhu@psu.edu
FU National Institutes of Health PHS grants [DK 077152, CA 162665]
FX National Institutes of Health PHS grants DK 077152 and CA 162665.
NR 37
TC 8
Z9 8
U1 1
U2 16
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0955-2863
EI 1873-4847
J9 J NUTR BIOCHEM
JI J. Nutr. Biochem.
PD FEB
PY 2015
VL 26
IS 2
BP 138
EP 145
DI 10.1016/j.jnutbio.2014.09.009
PG 8
WC Biochemistry & Molecular Biology; Nutrition & Dietetics
SC Biochemistry & Molecular Biology; Nutrition & Dietetics
GA CB4DL
UT WOS:000349578300005
PM 25458528
ER
PT J
AU Felisiak-Golabek, A
Wasag, B
Coates, T
Lasota, JP
Miettinen, M
AF Felisiak-Golabek, Anna
Wasag, Bartosz
Coates, Tiffany
Lasota, Jerzy P.
Miettinen, Markku
TI Frequency and Clinicopathologic Profile of PIK3CA Mutant GISTs
SO LABORATORY INVESTIGATION
LA English
DT Meeting Abstract
CT 104th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 21-27, 2015
CL Boston, MA
SP US & Canadian Acad Pathol
C1 NCI, Bethesda, MD 20892 USA.
Med Univ, Gdansk, Poland.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0023-6837
EI 1530-0307
J9 LAB INVEST
JI Lab. Invest.
PD FEB
PY 2015
VL 95
SU 1
MA 54
BP 17A
EP 17A
PG 1
WC Medicine, Research & Experimental; Pathology
SC Research & Experimental Medicine; Pathology
GA CA5KT
UT WOS:000348948000055
ER
PT J
AU Hsi, A
Brown, G
Lee, CC
Schaffer, A
AF Hsi, Andy
Brown, Gregory
Lee, Chyi-Chia
Schaffer, Andras
TI Expression of Master Regulators of Mature T-Cell Differentiation FOXP3,
T-Bet, and GATA-3 in Cutaneous Adult T-Cell Leukemia/Lymphoma By
Immunohistochemistry
SO LABORATORY INVESTIGATION
LA English
DT Meeting Abstract
CT 104th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 21-27, 2015
CL Boston, MA
SP US & Canadian Acad Pathol
C1 Washington Univ, Sch Med, St Louis, MO USA.
NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0023-6837
EI 1530-0307
J9 LAB INVEST
JI Lab. Invest.
PD FEB
PY 2015
VL 95
SU 1
MA 471
BP 121A
EP 121A
PG 1
WC Medicine, Research & Experimental; Pathology
SC Research & Experimental Medicine; Pathology
GA CA5KT
UT WOS:000348948000471
ER
PT J
AU Giubellino, A
Li, A
Lara-Otero, K
Linehan, M
Merino, M
AF Giubellino, Alessio
Li, Ang
Lara-Otero, Karlena
Linehan, Marston
Merino, Maria
TI MicroRNA Profiling of Morphologically Heterogeneous Clear Renal Cell
Carcinoma
SO LABORATORY INVESTIGATION
LA English
DT Meeting Abstract
CT 104th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 21-27, 2015
CL Boston, MA
SP US & Canadian Acad Pathol
C1 [Giubellino, Alessio; Li, Ang; Lara-Otero, Karlena; Linehan, Marston; Merino, Maria] NCI, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0023-6837
EI 1530-0307
J9 LAB INVEST
JI Lab. Invest.
PD FEB
PY 2015
VL 95
SU 1
MA 886
BP 223A
EP 223A
PG 1
WC Medicine, Research & Experimental; Pathology
SC Research & Experimental Medicine; Pathology
GA CA5KT
UT WOS:000348948001393
ER
PT J
AU Merino, M
Ghosh, A
Schmidt, L
Linehan, M
AF Merino, Maria
Ghosh, Arunima
Schmidt, Laura
Linehan, Marston
TI Clonal Analysis of Multi-Focal Tumors in Patients With Birt-Hogg-Dube
Syndrome
SO LABORATORY INVESTIGATION
LA English
DT Meeting Abstract
CT 104th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 21-27, 2015
CL Boston, MA
SP US & Canadian Acad Pathol
C1 NCI, Bethesda, MD 20892 USA.
Frederick Natl Lab, Frederick, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0023-6837
EI 1530-0307
J9 LAB INVEST
JI Lab. Invest.
PD FEB
PY 2015
VL 95
SU 1
MA 975
BP 245A
EP 245A
PG 1
WC Medicine, Research & Experimental; Pathology
SC Research & Experimental Medicine; Pathology
GA CA5KT
UT WOS:000348948001482
ER
PT J
AU Moreno, V
Metwali, A
Linehan, WM
Merino, M
AF Moreno, Vanessa
Metwali, Adam
Linehan, W. Marston
Merino, Maria
TI New and Old Testicular Lesions Associated With VHL Syndrome
SO LABORATORY INVESTIGATION
LA English
DT Meeting Abstract
CT 104th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 21-27, 2015
CL Boston, MA
SP US & Canadian Acad Pathol
C1 [Moreno, Vanessa; Metwali, Adam; Linehan, W. Marston; Merino, Maria] NCI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0023-6837
EI 1530-0307
J9 LAB INVEST
JI Lab. Invest.
PD FEB
PY 2015
VL 95
SU 1
MA 979
BP 246A
EP 246A
PG 1
WC Medicine, Research & Experimental; Pathology
SC Research & Experimental Medicine; Pathology
GA CA5KT
UT WOS:000348948001486
ER
PT J
AU Yan, WS
Young, D
Song, YJ
Chen, YM
Katta, S
Ravindranath, L
Lee, J
Srinivasan, A
Cullen, J
Kagan, J
Srivastava, S
Dobi, A
Rosner, I
McLeod, D
Sesterhenn, I
Srivastava, S
Petrovics, G
AF Yan, Wusheng
Young, Denise
Song, Yingjie
Chen, Yongmei
Katta, Shilpa
Ravindranath, Lakshmi
Lee, Jocelyn
Srinivasan, Alagarsamy
Cullen, Jennifer
Kagan, Jacob
Srivastava, Sudhir
Dobi, Albert
Rosner, Inger
McLeod, David
Sesterhenn, Isabell
Srivastava, Shiv
Petrovics, Gyotgy
TI Optimization of Nanostring Platform for Evaluation of Prostate Cancer
Biomarkers and Therapeutic Targes in FFPE Specimens
SO LABORATORY INVESTIGATION
LA English
DT Meeting Abstract
CT 104th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 21-27, 2015
CL Boston, MA
SP US & Canadian Acad Pathol
C1 Uniformed Serv Univ Hlth Sci, Rockville, MD USA.
NCI, Rockville, MD USA.
Walter Reed Natl Mil Med Ctr, Bethesda, MD USA.
Joint Pathol Ctr, Silver Spring, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0023-6837
EI 1530-0307
J9 LAB INVEST
JI Lab. Invest.
PD FEB
PY 2015
VL 95
SU 1
MA 1070
BP 268A
EP 269A
PG 2
WC Medicine, Research & Experimental; Pathology
SC Research & Experimental Medicine; Pathology
GA CA5KT
UT WOS:000348948002089
ER
PT J
AU Yang, ZM
Li, A
Pinto, P
Merino, M
AF Yang, Zhiming
Li, Ang
Pinto, Peter
Merino, Maria
TI microRNA Profiling of Prostate Cancer in Young and Older Man, One or Two
Diseases?
SO LABORATORY INVESTIGATION
LA English
DT Meeting Abstract
CT 104th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 21-27, 2015
CL Boston, MA
SP US & Canadian Acad Pathol
C1 [Yang, Zhiming; Li, Ang; Pinto, Peter; Merino, Maria] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0023-6837
EI 1530-0307
J9 LAB INVEST
JI Lab. Invest.
PD FEB
PY 2015
VL 95
SU 1
MA 1072
BP 269A
EP 269A
PG 1
WC Medicine, Research & Experimental; Pathology
SC Research & Experimental Medicine; Pathology
GA CA5KT
UT WOS:000348948002091
ER
PT J
AU Zheng, XY
Mao, Y
Huang, W
Kamalakaran, S
Yang, Y
Linehan, WM
Merino, MJ
Zhong, MH
Dimitrova, N
Fallon, J
AF Zheng, Xiaoyong
Mao, Yong
Huang, Weihua
Kamalakaran, Sitharthan
Yang, Youfeng
Linehan, W. Marston
Merino, Maria J.
Zhong, Minghao
Dimitrova, Nevenka
Fallon, John
TI Detecting Additional Chromosomal Translocations in TFE3 Translocation
Renal Cell RCC By RNA-Seq
SO LABORATORY INVESTIGATION
LA English
DT Meeting Abstract
CT 104th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 21-27, 2015
CL Boston, MA
SP US & Canadian Acad Pathol
C1 New York Med Coll, Westchester Med Ctr, Valhalla, NY 10595 USA.
Philips Res North Amer, Briarcliff Manor, NY USA.
NCI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0023-6837
EI 1530-0307
J9 LAB INVEST
JI Lab. Invest.
PD FEB
PY 2015
VL 95
SU 1
MA 1080
BP 271A
EP 271A
PG 1
WC Medicine, Research & Experimental; Pathology
SC Research & Experimental Medicine; Pathology
GA CA5KT
UT WOS:000348948002099
ER
PT J
AU Gong, SY
Townsley, D
Hsu, A
Arthur, D
Giri, N
Alter, B
Hickstein, D
Young, N
Braylan, R
Holland, S
Calvo, K
AF Gong, Shunyou
Townsley, Danielle
Hsu, Amy
Arthur, Diane
Giri, Neelam
Alter, Blanche
Hickstein, Dennis
Young, Neal
Braylan, Raul
Holland, Steven
Calvo, Katherine
TI Atypical Myelofibrosis in Patients Harboring Germline GATA2 Mutations
SO LABORATORY INVESTIGATION
LA English
DT Meeting Abstract
CT 104th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 21-27, 2015
CL Boston, MA
SP US & Canadian Acad Pathol
C1 [Gong, Shunyou; Townsley, Danielle; Hsu, Amy; Arthur, Diane; Giri, Neelam; Alter, Blanche; Hickstein, Dennis; Young, Neal; Braylan, Raul; Holland, Steven; Calvo, Katherine] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0023-6837
EI 1530-0307
J9 LAB INVEST
JI Lab. Invest.
PD FEB
PY 2015
VL 95
SU 1
MA 1384
BP 346A
EP 346A
PG 1
WC Medicine, Research & Experimental; Pathology
SC Research & Experimental Medicine; Pathology
GA CA5KT
UT WOS:000348948002402
ER
PT J
AU Gong, SY
Dumitriu, B
Young, N
Maric, I
AF Gong, Shunyou
Dumitriu, Bogdan
Young, Neal
Maric, Irina
TI Evaluation of Phospho-STAT3 Immunohistochemical Stain in Diagnosis of
Marrow Involvement By Large Granular Lymphocytic Leukemia
SO LABORATORY INVESTIGATION
LA English
DT Meeting Abstract
CT 104th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 21-27, 2015
CL Boston, MA
SP US & Canadian Acad Pathol
C1 NHLBI, Bethesda, MD 20892 USA.
NIH, Ctr Clin, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0023-6837
EI 1530-0307
J9 LAB INVEST
JI Lab. Invest.
PD FEB
PY 2015
VL 95
SU 1
MA 1385
BP 346A
EP 346A
PG 1
WC Medicine, Research & Experimental; Pathology
SC Research & Experimental Medicine; Pathology
GA CA5KT
UT WOS:000348948002403
ER
PT J
AU King, R
Dao, L
McPhail, E
Jaffe, E
Said, J
Swerdlow, S
Sidhu, J
Hsi, E
Karikehalli, S
Jiang, LY
Gibson, S
Ondrejka, S
Nicolae, A
Macon, W
Castellar, EP
Feldman, AL
AF King, Rebecca
Dao, Linda
McPhail, Ellen
Jaffe, Elaine
Said, Jonathan
Swerdlow, Steven
Sidhu, Jagmohan
Hsi, Eric
Karikehalli, Shrideyi
Jiang, Liuyan
Gibson, Sarah
Ondrejka, Sarah
Nicolae, Alina
Macon, William
Castellar, Edgardo Parrilla
Feldman, Andrew L.
TI Morphology of ALK-Negative Anaplastic Large Cell Lymphomas With DUSP22
Rearrangements
SO LABORATORY INVESTIGATION
LA English
DT Meeting Abstract
CT 104th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 21-27, 2015
CL Boston, MA
SP US & Canadian Acad Pathol
C1 Mayo Clin, Rochester, MN USA.
NCI, Bethesda, MD 20892 USA.
Univ Calif Los Angeles, Los Angeles, CA USA.
Univ Pittsburgh, Pittsburgh, PA USA.
United Hlth Serv Hopsitals, Binghamton, NY USA.
Cleveland Clin, Cleveland, OH 44106 USA.
Centrex Clin Labs, Utica, NY USA.
Univ Washington, Seattle, WA 98195 USA.
Mayo Clin, Jacksonville, FL 32224 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0023-6837
EI 1530-0307
J9 LAB INVEST
JI Lab. Invest.
PD FEB
PY 2015
VL 95
SU 1
MA 1416
BP 355A
EP 355A
PG 1
WC Medicine, Research & Experimental; Pathology
SC Research & Experimental Medicine; Pathology
GA CA5KT
UT WOS:000348948002434
ER
PT J
AU Nicolae, A
Ganapathi, K
Pittaluga, S
Raffeld, M
Jaffe, E
AF Nicolae, Alina
Ganapathi, Karthik
Pittaluga, Stefania
Raffeld, Mark
Jaffe, Elaine
TI Aggressive NK-Cell Leukemia/Lymphoma, EBV-Negative - A Report of 5 Cases
SO LABORATORY INVESTIGATION
LA English
DT Meeting Abstract
CT 104th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 21-27, 2015
CL Boston, MA
SP US & Canadian Acad Pathol
C1 NCI, Bethesda, MD 20892 USA.
Columbia Univ, New York, NY USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0023-6837
EI 1530-0307
J9 LAB INVEST
JI Lab. Invest.
PD FEB
PY 2015
VL 95
SU 1
MA 1465
BP 368A
EP 368A
PG 1
WC Medicine, Research & Experimental; Pathology
SC Research & Experimental Medicine; Pathology
GA CA5KT
UT WOS:000348948002483
ER
PT J
AU Wang, HW
Pittaluga, S
Merino, M
Jaffe, E
AF Wang, Hao-Wei
Pittaluga, Stefania
Merino, Maria
Jaffe, Elaine
TI Primary Malignant Lymphomas of the Urinary Tract
SO LABORATORY INVESTIGATION
LA English
DT Meeting Abstract
CT 104th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 21-27, 2015
CL Boston, MA
SP US & Canadian Acad Pathol
C1 [Wang, Hao-Wei; Pittaluga, Stefania; Merino, Maria; Jaffe, Elaine] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0023-6837
EI 1530-0307
J9 LAB INVEST
JI Lab. Invest.
PD FEB
PY 2015
VL 95
SU 1
MA 1526
BP 383A
EP 384A
PG 2
WC Medicine, Research & Experimental; Pathology
SC Research & Experimental Medicine; Pathology
GA CA5KT
UT WOS:000348948003027
ER
PT J
AU Yousef, G
Butz, H
Szabo, P
Mozes, R
Rotondo, F
Kovacs, K
Patocs, A
AF Yousef, George
Butz, Henriett
Szabo, Peter
Mozes, Roy
Rotondo, Fabio
Kovacs, Kalman
Patocs, Attila
TI Integrative Bioinformatical Analysis of Clear Cell Renal Cell Carcinoma
SO LABORATORY INVESTIGATION
LA English
DT Meeting Abstract
CT 104th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 21-27, 2015
CL Boston, MA
SP US & Canadian Acad Pathol
C1 St Michaels Hosp, Toronto, ON M5B 1W8, Canada.
NCI, NIH, Bethesda, MD 20892 USA.
Hungarian Acad Sci, Budapest, Hungary.
NR 0
TC 0
Z9 0
U1 1
U2 2
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0023-6837
EI 1530-0307
J9 LAB INVEST
JI Lab. Invest.
PD FEB
PY 2015
VL 95
SU 1
MA 1604
BP 403A
EP 403A
PG 1
WC Medicine, Research & Experimental; Pathology
SC Research & Experimental Medicine; Pathology
GA CA5KT
UT WOS:000348948003105
ER
PT J
AU Rosenberg, A
Palmer, M
Merlino, L
Troost, J
Gasim, A
Bagnasco, SM
Avila-Casado, C
Johnstone, D
Hodgin, J
Conway, C
Kopp, J
Nast, C
Barisoni, L
Hewitt, S
AF Rosenberg, Avi
Palmer, Matthew
Merlino, Lino
Troost, Jonathan
Gasim, Adil
Bagnasco, Serena M.
Avila-Casado, Carmen
Johnstone, Duncan
Hodgin, Jeffrey
Conway, Catherine
Kopp, Jeffrey
Nast, Cynthia
Barisoni, Laura
Hewitt, Stephen
TI The NEPTUNE Digital Pathology Protocol Increases Accurate Glomerular
Number Assessment
SO LABORATORY INVESTIGATION
LA English
DT Meeting Abstract
CT 104th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 21-27, 2015
CL Boston, MA
SP US & Canadian Acad Pathol
C1 Johns Hopkins Univ, Baltimore, MD USA.
Univ Penn, Philadelphia, PA 19104 USA.
Univ Miami, Miami, FL USA.
Univ Michigan, Ann Arbor, MI 48109 USA.
Univ N Carolina, Chapel Hill, NC USA.
Univ Hlth Network, Toronto, ON, Canada.
Temple Univ, Philadelphia, PA 19122 USA.
Leica, Vista, CA USA.
NIDDK, Bethesda, MD 20892 USA.
Cedars Sinai Med Ctr, West Hollywood, CA USA.
NCI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0023-6837
EI 1530-0307
J9 LAB INVEST
JI Lab. Invest.
PD FEB
PY 2015
VL 95
SU 1
MA 1639
BP 411A
EP 412A
PG 2
WC Medicine, Research & Experimental; Pathology
SC Research & Experimental Medicine; Pathology
GA CA5KT
UT WOS:000348948003140
ER
PT J
AU Ballester, L
Wang, Z
Miettinen, M
Rodriguez, F
Raabe, E
Nazarian, J
Eberhart, C
Warren, K
Quezado, M
AF Ballester, Leomar
Wang, Zengfeng
Miettinen, Markku
Rodriguez, Fausto
Raabe, Eric
Nazarian, Javad
Eberhart, Charles
Warren, Katherine
Quezado, Martha
TI Overexpression of the Chromatin Remodeling Proteins ARID1A, BRG1 and
SMARCD3 in Adult and Pediatric Gliomas
SO LABORATORY INVESTIGATION
LA English
DT Meeting Abstract
CT 104th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 21-27, 2015
CL Boston, MA
SP US & Canadian Acad Pathol
C1 NCI, NIH, Bethesda, MD 20892 USA.
Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA.
Childrens Res Inst, Washington, DC USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0023-6837
EI 1530-0307
J9 LAB INVEST
JI Lab. Invest.
PD FEB
PY 2015
VL 95
SU 1
MA 1711
BP 428A
EP 429A
PG 2
WC Medicine, Research & Experimental; Pathology
SC Research & Experimental Medicine; Pathology
GA CA5KT
UT WOS:000348948003211
ER
PT J
AU Ghosh, A
Li, A
Brown, G
Kebebew, E
Merino, M
AF Ghosh, Arunima
Li, Ang
Brown, Gregory
Kebebew, Electron
Merino, Maria
TI Multifocal Pancreatic Neuroendocrine Tumors: Clonality and miRNA
Profiling
SO LABORATORY INVESTIGATION
LA English
DT Meeting Abstract
CT 104th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 21-27, 2015
CL Boston, MA
SP US & Canadian Acad Pathol
C1 [Ghosh, Arunima; Li, Ang; Brown, Gregory; Kebebew, Electron; Merino, Maria] NCI, Rockville, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0023-6837
EI 1530-0307
J9 LAB INVEST
JI Lab. Invest.
PD FEB
PY 2015
VL 95
SU 1
MA 1771
BP 442A
EP 442A
PG 1
WC Medicine, Research & Experimental; Pathology
SC Research & Experimental Medicine; Pathology
GA CA5KT
UT WOS:000348948003271
ER
PT J
AU Rosenberg, A
Pflicke, H
Dreiling, J
Wang, ZF
Ylaya, K
Hewitt, S
Rudloff, U
Miettinen, M
AF Rosenberg, Avi
Pflicke, Holger
Dreiling, Jennifer
Wang, Zeng-Feng
Ylaya, Kris
Hewitt, Stephen
Rudloff, Udo
Miettinen, Markku
TI Elafin Expression in Gastrointestinal Neoplasia and Correlation With
Sensitivity To PI3K/mTOR Inhibitor
SO LABORATORY INVESTIGATION
LA English
DT Meeting Abstract
CT 104th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 21-27, 2015
CL Boston, MA
SP US & Canadian Acad Pathol
C1 Johns Hopkins Univ, Baltimore, MD USA.
NCI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0023-6837
EI 1530-0307
J9 LAB INVEST
JI Lab. Invest.
PD FEB
PY 2015
VL 95
SU 1
MA 1791
BP 447A
EP 447A
PG 1
WC Medicine, Research & Experimental; Pathology
SC Research & Experimental Medicine; Pathology
GA CA5KT
UT WOS:000348948003291
ER
PT J
AU Schlitter, A
Jang, KT
Saka, B
Choi, H
Offerhaus, G
Hruban, R
Zen, Y
Hong, SM
Konukiewitz, B
Allgaeuer, M
Kloppel, G
Reid, M
Esposito, I
Adsay, V
Basturk, O
AF Schlitter, Anna
Jang, Kee-Taek
Saka, Burcu
Choi, Hyejeong
Offerhaus, G.
Hruban, R.
Zen, Yoh
Hong, Seung-Mo
Konukiewitz, Bjorn
Allgaeuer, Michael
Kloppel, G.
Reid, M.
Esposito, Irene
Adsay, Volkan
Basturk, Olca
TI Intraductal Tubulopapillary Neoplasms of the Bile Ducts: Further
Immunohistochemical and Molecular Characterization
SO LABORATORY INVESTIGATION
LA English
DT Meeting Abstract
CT 104th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 21-27, 2015
CL Boston, MA
SP US & Canadian Acad Pathol
C1 TUM, Munich, Germany.
SMC, Seoul, South Korea.
EU, Atlanta, GA USA.
Univ Med Ctr, Utrecht, Netherlands.
Johns Hopkins Univ, Baltimore, MD USA.
KCH, London, England.
Asan Med Ctr, Seoul, South Korea.
NCI, NIH, Bethesda, MD 20892 USA.
Wayne State Univ, Detroit, MI USA.
NR 0
TC 0
Z9 0
U1 1
U2 2
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0023-6837
EI 1530-0307
J9 LAB INVEST
JI Lab. Invest.
PD FEB
PY 2015
VL 95
SU 1
MA 1795
BP 448A
EP 448A
PG 1
WC Medicine, Research & Experimental; Pathology
SC Research & Experimental Medicine; Pathology
GA CA5KT
UT WOS:000348948003295
ER
PT J
AU Jawale, R
Williams, K
Yang, H
Lee, M
Otis, C
Pentecost, B
Arcaro, K
AF Jawale, Rahul
Williams, Kristin
Yang, Howard
Lee, Maxwell
Otis, Christopher
Pentecost, Brian
Arcaro, Kathleen
TI DNA Methylation in Endocrine Therapy Resistant Breast Cancer
SO LABORATORY INVESTIGATION
LA English
DT Meeting Abstract
CT 104th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 21-27, 2015
CL Boston, MA
SP US & Canadian Acad Pathol
C1 Baystate Med Ctr, Springfield, MA USA.
UMass Amherst, Amherst, MA USA.
Wadsworth Ctr, Albany, NY USA.
NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0023-6837
EI 1530-0307
J9 LAB INVEST
JI Lab. Invest.
PD FEB
PY 2015
VL 95
SU 1
MA 1837
BP 458A
EP 459A
PG 2
WC Medicine, Research & Experimental; Pathology
SC Research & Experimental Medicine; Pathology
GA CA5KT
UT WOS:000348948003337
ER
PT J
AU Killian, J
Noyes, N
Retnakumar, P
Helman, L
Killian, S
Davis, S
Bilke, S
Su, J
Smith, W
Meltzer, P
AF Killian, Jonathan
Noyes, Natalia
Retnakumar, Parvathy
Helman, Lee
Killian, Scott
Davis, Sean
Bilke, Sven
Su, Joseph
Smith, William
Meltzer, Paul
TI Cellular and Epiallelic Composition of Oral Fluid
SO LABORATORY INVESTIGATION
LA English
DT Meeting Abstract
CT 104th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 21-27, 2015
CL Boston, MA
SP US & Canadian Acad Pathol
C1 NCI, Bethesda, MD 20892 USA.
Univ S Dakota, Vermillion, SD 57069 USA.
Suburban Hosp, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 2
U2 2
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0023-6837
EI 1530-0307
J9 LAB INVEST
JI Lab. Invest.
PD FEB
PY 2015
VL 95
SU 1
MA 1839
BP 459A
EP 459A
PG 1
WC Medicine, Research & Experimental; Pathology
SC Research & Experimental Medicine; Pathology
GA CA5KT
UT WOS:000348948003339
ER
PT J
AU Makhlouf, H
Lubensky, I
Altekruse, S
Mehaffey, M
Sachs, M
Camalier, C
Chuaqui, R
Cozen, W
Biswajit, D
Hernandez, B
Lih, CJ
Lynch, C
McGregor, P
McShane, L
Rohan, JP
Walsh, W
Williams, M
Gillanders, E
Mechanic, L
Schully, S
Carrick, D
AF Makhlouf, Hala
Lubensky, Irina
Altekruse, Sean
Mehaffey, Michele
Sachs, Michael
Camalier, Corinne
Chuaqui, Rodrigo
Cozen, Wendy
Biswajit, Das
Hernandez, Brenda
Lih, Chih-Jian
Lynch, Charles
McGregor, Paul
McShane, Lisa
Rohan, JoyAnn Philips
Walsh, William
Williams, Mickey
Gillanders, Elizabeth
Mechanic, Leah
Schully, Sheri
Carrick, Danielle
TI Effect of Storage Time of FFPE Ovarian Cancer Tissue on DNA Quality for
Next Generation Sequencing
SO LABORATORY INVESTIGATION
LA English
DT Meeting Abstract
CT 104th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 21-27, 2015
CL Boston, MA
SP US & Canadian Acad Pathol
C1 NCI, Rockville, MD USA.
Leidos, Frederick, MD USA.
Univ So Calif, Los Angeles, CA USA.
Univ Hawaii, Ctr Canc, Honolulu, HI 96822 USA.
Univ Iowa, Iowa City, IA USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0023-6837
EI 1530-0307
J9 LAB INVEST
JI Lab. Invest.
PD FEB
PY 2015
VL 95
SU 1
MA 2084
BP 519A
EP 519A
PG 1
WC Medicine, Research & Experimental; Pathology
SC Research & Experimental Medicine; Pathology
GA CA5KT
UT WOS:000348948003583
ER
PT J
AU Miles, G
Zhao, YM
Levin, Y
Shetty, J
Tran, B
Mitchell, S
Oberholtzer, JC
Levens, D
AF Miles, George
Zhao, Yongmei
Levin, Yelena
Shetty, Jyoti
Tran, Bao
Mitchell, Stephen
Oberholtzer, J. Carl
Levens, David
TI Multiplex Tissue and Clinical Proteomics By Next-Generation Sequencing
SO LABORATORY INVESTIGATION
LA English
DT Meeting Abstract
CT 104th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 21-27, 2015
CL Boston, MA
SP US & Canadian Acad Pathol
C1 NCI, Bethesda, MD 20892 USA.
Frederick Natl Lab, Frederick, MD USA.
Holy Cross Hosp, Silver Spring, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0023-6837
EI 1530-0307
J9 LAB INVEST
JI Lab. Invest.
PD FEB
PY 2015
VL 95
SU 1
MA 2089
BP 520A
EP 520A
PG 1
WC Medicine, Research & Experimental; Pathology
SC Research & Experimental Medicine; Pathology
GA CA5KT
UT WOS:000348948003588
ER
PT J
AU Rosenberg, A
Armani, M
Fetsch, P
Xi, LQ
Pham, TT
Raffeld, M
Chen, Y
O'Flaherty, N
Stussman, R
Blackler, A
Du, Q
Hanson, J
Roth, M
Filie, A
Roh, M
Emmert-Buck, M
Hipp, J
Tangrea, M
AF Rosenberg, Avi
ArmaniIrm, Michael M
Fetsch, Patricia
Xi, Liqiang
Tina Thu Pham
Raffeld, Mark
Chen, Yun
O'Flaherty, Neil
Stussman, Rebecca
Blackler, Adele
Du, Qiang
Hanson, Jeffrey
Roth, Mark
Filie, Armando
Roh, Michael
Emmert-Buck, Michael
Hipp, Jason
Tangrea, Michael
TI A Do-It-Yourself, High-Throughput Microdissection System for Improving
NGS Data
SO LABORATORY INVESTIGATION
LA English
DT Meeting Abstract
CT 104th Annual Meeting of the
United-States-and-Canadian-Academy-of-Pathology
CY MAR 21-27, 2015
CL Boston, MA
SP US & Canadian Acad Pathol
C1 Johns Hopkins Sch Med, Baltimore, MD USA.
NCI, Bethesda, MD 20892 USA.
Univ Michigan, Ann Arbor, MI 48109 USA.
Sinai Hosp, Baltimore, MD 21215 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0023-6837
EI 1530-0307
J9 LAB INVEST
JI Lab. Invest.
PD FEB
PY 2015
VL 95
SU 1
MA 2099
BP 523A
EP 523A
PG 1
WC Medicine, Research & Experimental; Pathology
SC Research & Experimental Medicine; Pathology
GA CA5KT
UT WOS:000348948003598
ER
PT J
AU Mani, R
Mao, Y
Frissora, FW
Chiang, CL
Wang, J
Zhao, Y
Wu, Y
Yu, B
Yan, R
Mo, X
Yu, L
Flynn, J
Jones, J
Andritsos, L
Baskar, S
Rader, C
Phelps, MA
Chen, CS
Lee, RJ
Byrd, JC
Lee, LJ
Muthusamy, N
AF Mani, R.
Mao, Y.
Frissora, F. W.
Chiang, C-L
Wang, J.
Zhao, Y.
Wu, Y.
Yu, B.
Yan, R.
Mo, X.
Yu, L.
Flynn, J.
Jones, J.
Andritsos, L.
Baskar, S.
Rader, C.
Phelps, M. A.
Chen, C-S
Lee, R. J.
Byrd, J. C.
Lee, L. J.
Muthusamy, N.
TI Tumor antigen ROR1 targeted drug delivery mediated selective leukemic
but not normal B-cell cytotoxicity in chronic lymphocytic leukemia
SO LEUKEMIA
LA English
DT Article
ID PROTEIN-TYROSINE-PHOSPHATASE; KINASE-C; HEPATOCELLULAR-CARCINOMA;
ABERRANT METHYLATION; MYELOGENOUS LEUKEMIA; PRECLINICAL ACTIVITY;
DOWN-REGULATION; LYMPHOMA-CELLS; SHP-1; FTY720
AB Selective cytotoxicity to cancer cells without compromising their normal counterparts pose a huge challenge for traditional drug design. Here we developed a tumor antigen-targeted delivery of immunonanoparticle carrying a novel non-immunosuppressive FTY720 derivative OSU-2S with potent cytotoxicity against leukemic B cells. OSU-2S induces activation of protein phosphatase 2A (PP2A), phosphorylation and nuclear translocation of SHP1(S591) and deregulation of multiple cellular processes in chronic lymphocytic leukemia (CLL) resulting in potent cytotoxicity. To preclude OSU-2S-mediated effects on these ubiquitous phosphatases in unintended cells and avoid potential adverse effects, we developed an OSU-2S-targeted delivery of immunonanoparticles (2A2-OSU-2S-ILP), that mediated selective cytotoxicity of CLL but not normal B cells through targeting receptor tyrosine kinase ROR1 expressed in leukemic but not normal B cells. Developing a novel spontaneous CLL mouse model expressing human ROR1 (hROR1) in all leukemic B cells, we demonstrate the therapeutic benefit of enhanced survival with 2A2-OSU-2S-ILP in vivo. The newly developed non-immunosuppressive OSU-2S, its delivery using human CLL directed immunonanoparticles and the novel transgenic (Tg) mouse model of CLL that expresses hROR1 exclusively in leukemic B cell surface are highly innovative and can be applied to CLL and other ROR1 + malignancies including mantle cell lymphoma and acute lymphoblastic leukemia.
C1 [Mani, R.; Frissora, F. W.; Chiang, C-L; Flynn, J.; Jones, J.; Andritsos, L.; Byrd, J. C.; Muthusamy, N.] Ohio State Univ, Coll Med, Dept Internal Med, Div Hematol, Columbus, OH 43210 USA.
[Mani, R.; Mao, Y.; Frissora, F. W.; Chiang, C-L; Wang, J.; Yu, B.; Phelps, M. A.; Chen, C-S; Lee, R. J.; Byrd, J. C.; Muthusamy, N.] Ohio State Univ, Comprehens Canc Ctr, Columbus, OH 43210 USA.
[Mani, R.; Chen, C-S; Byrd, J. C.; Muthusamy, N.] Ohio State Univ, Coll Vet Med, Dept Vet Biosci, Columbus, OH 43210 USA.
[Mao, Y.; Zhao, Y.; Phelps, M. A.; Lee, R. J.] Ohio State Univ, Coll Pharm, Div Pharmaceut, Columbus, OH 43210 USA.
[Mao, Y.; Wu, Y.; Yu, B.; Lee, R. J.; Lee, L. J.] Ohio State Univ, Ctr Affordable Nanoengn Polymer Biomed Devices, Columbus, OH 43210 USA.
[Yan, R.; Chen, C-S; Byrd, J. C.] Ohio State Univ, Coll Pharm, Div Med Chem, Columbus, OH 43210 USA.
[Mo, X.; Yu, L.] Ohio State Univ, Ctr Biostat, Columbus, OH 43210 USA.
[Baskar, S.] NCI, Pediat Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Rader, C.] Scripps Res Inst, Dept Canc Biol, Jupiter, FL USA.
[Rader, C.] Scripps Res Inst, Dept Mol Therapeut, Jupiter, FL USA.
[Lee, L. J.] Ohio State Univ, Dept Chem & Biomol Engn, Columbus, OH 43210 USA.
RP Muthusamy, N (reprint author), Ohio State Univ, Ctr Comprehens Canc, Dept Internal Med Mol Virol Immunol & Med Genet &, Div Hematol,OSUCCC, 455E,410,West 12th Ave, Columbus, OH 43210 USA.
EM raj.muthusamy@osumc.edu
RI Mani, Rajeswaran/Q-2762-2015; Jones, Jeffrey/E-3321-2011; Chiang,
Chi-Ling/O-3038-2016
OI Chiang, Chi-Ling/0000-0002-0275-9673
FU Leukemia & Lymphoma Society Specialized Center of Research (SCOR) in
leukemia [LLS 7004-11, NCI-P50-CA140158]; Harry Mangurian Foundation; D
Warren Brown Foundation; Robert J Anthony Fund; NSF [NSEC EEC-0914790]
FX We are thankful to the patients who supported this research by providing
their blood. This work was funded by Leukemia & Lymphoma Society
Specialized Center of Research (SCOR) in leukemia grant LLS 7004-11,
NCI-P50-CA140158, Harry Mangurian Foundation, D Warren Brown Foundation,
Robert J Anthony Fund and NSF grant NSEC EEC-0914790.
NR 52
TC 13
Z9 13
U1 1
U2 9
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 FEB
PY 2015
VL 29
IS 2
BP 346
EP 355
DI 10.1038/leu.2014.199
PG 10
WC Oncology; Hematology
SC Oncology; Hematology
GA CB2GL
UT WOS:000349445000011
PM 24947019
ER
PT J
AU Suryani, S
Bracken, LS
Harvey, RC
Sia, KCS
Carol, H
Chen, IM
Evans, K
Dietrich, PA
Roberts, KG
Kurmasheva, RT
Billups, CA
Mullighan, CG
Willman, CL
Loh, ML
Hunger, SP
Houghton, PJ
Smith, MA
Lock, RB
AF Suryani, Santi
Bracken, Lauryn S.
Harvey, Richard C.
Sia, Keith C. S.
Carol, Hernan
Chen, I-Ming
Evans, Kathryn
Dietrich, Philipp A.
Roberts, Kathryn G.
Kurmasheva, Raushan T.
Billups, Catherine A.
Mullighan, Charles G.
Willman, Cheryl L.
Loh, Mignon L.
Hunger, Stephen P.
Houghton, Peter J.
Smith, Malcolm A.
Lock, Richard B.
TI Evaluation of the In Vitro and In Vivo Efficacy of the JAK Inhibitor
AZD1480 against JAK-Mutated Acute Lymphoblastic Leukemia
SO MOLECULAR CANCER THERAPEUTICS
LA English
DT Article
ID PRECLINICAL TESTING PROGRAM; CELL-CYCLE PROGRESSION; B-PROGENITOR;
XENOGRAFT MODELS; BREAST-CANCER; SOLID TUMORS; PHASE-I; CRLF2; PATHWAY;
KINASE
AB Genome-wide studies have identified a high-risk subgroup of pediatric acute lymphoblastic leukemia (ALL) harboring mutations in the Janus kinases (JAK). The purpose of this study was to assess the preclinical efficacy of the JAK1/2 inhibitor AZD1480, both as a single agent and in combination with the MEK inhibitor selumetinib, against JAK-mutated patient-derived xenografts. Patient-derived xenografts were established in immunodeficient mice from bone marrow or peripheral blood biopsy specimens, and their gene expression profiles compared with the original patient biopsies by microarray analysis. JAK/STAT and MAPK signaling pathways, and the inhibitory effects of targeted drugs, were interrogated by immunoblotting of phosphoproteins. The antileukemic effects of AZD1480 and selumetinib, alone and in combination, were tested against JAK-mutated ALL xenografts both in vitro and in vivo. Xenografts accurately represented the primary disease as determined by gene expression profiling. Cellular phosphoprotein analysis demonstrated that JAK-mutated xenografts exhibited heightened activation status of JAK/STAT and MAPK signaling pathways compared with typical B-cell precursor ALL xenografts, which were inhibited by AZD1480 exposure. However, AZD1480 exhibited modest single-agent in vivo efficacy against JAK-mutated xenografts. Combining AZD1480 with selumetinib resulted in profound synergistic in vitro cell killing, although these results were not translated in vivo despite evidence of target inhibition. Despite validation of target inhibition and the demonstration of profound in vitro synergy between AZD1480 and selumetinib, it is likely that prolonged target inhibition is required to achieve in vivo therapeutic enhancement between JAK and MEK inhibitors in the treatment of JAKmutated ALL. (C) 2014 AACR.
C1 [Suryani, Santi; Bracken, Lauryn S.; Sia, Keith C. S.; Carol, Hernan; Evans, Kathryn; Dietrich, Philipp A.; Lock, Richard B.] Univ New S Wales, Lowy Canc Res Ctr, Childrens Canc Inst Australia Med Res, Sydney, NSW 2031, Australia.
[Harvey, Richard C.; Chen, I-Ming; Willman, Cheryl L.] Univ New Mexico, Ctr Canc, Albuquerque, NM 87131 USA.
[Evans, Kathryn; Mullighan, Charles G.] St Jude Childrens Res Hosp, Dept Pathol, Memphis, TN 38105 USA.
[Kurmasheva, Raushan T.; Houghton, Peter J.] Nationwide Childrens Hosp, Ctr Childhood Canc, Columbus, OH USA.
[Billups, Catherine A.] St Jude Childrens Res Hosp, Dept Biostat, Memphis, TN 38105 USA.
[Loh, Mignon L.] Univ Calif San Francisco, Dept Pediat, San Francisco, CA USA.
[Hunger, Stephen P.] Univ Colorado Denver, Sch Med, Aurora, CO USA.
[Hunger, Stephen P.] Univ Colorado Denver, Childrens Hosp Colorado, Aurora, CO USA.
[Smith, Malcolm A.] NCI, CTEP, Bethesda, MD 20892 USA.
RP Lock, RB (reprint author), Univ New S Wales, Lowy Canc Res Ctr, Childrens Canc Inst Australia Med Res, POB 81, Sydney, NSW 2031, Australia.
EM rlock@ccia.unsw.edu.au
RI Lock, Richard/G-4253-2013;
OI Harvey, Richard/0000-0002-4904-9767; Mullighan,
Charles/0000-0002-1871-1850
FU National Cancer Institute [NOI-CM-42216, NOI-CM-91001-03, CA98543,
CA98413, CA114766]; Leukaemia Foundation of Australia; Cure Cancer
Australia Foundation; Cancer Institute NSW; National Health and Medical
Research Council
FX This research was funded by grants from the National Cancer Institute
including NOI-CM-42216 and NOI-CM-91001-03 (to P. J. Houghton), CA98543
(COG Chair's grant), CA98413 (COG Statistical Center) and CA114766 (COG
Specimen Banking; to S. P. Hunger). S. Suryani is supported by
Postdoctoral Fellowships from the Leukaemia Foundation of Australia and
the Cure Cancer Australia Foundation, and an Early Career Fellowship
from the Cancer Institute NSW. S. P. Hunger is the Ergen Family Chair in
Pediatric Cancer. R. B. Lock is supported by a Fellowship from the
National Health and Medical Research Council.
NR 39
TC 7
Z9 7
U1 0
U2 7
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 FEB
PY 2015
VL 14
IS 2
BP 364
EP 374
DI 10.1158/1535-7163.MCT-14-0647
PG 11
WC Oncology
SC Oncology
GA CB3OV
UT WOS:000349538700005
PM 25504635
ER
PT J
AU Weiss, K
Gonzalez, AN
Lopez, G
Pedoeim, L
Groden, C
Sidransky, E
AF Weiss, Karin
Gonzalez, Ashley N.
Lopez, Grisel
Pedoeim, Leah
Groden, Catherine
Sidransky, Ellen
TI The clinical management of type 2 Gaucher disease
SO MOLECULAR GENETICS AND METABOLISM
LA English
DT Review
DE Gaucher disease; Acute neuronopathic; Lysosomal storage disorder;
Hydrops fetalis; Congenital ichthyosis; Palliative care
ID ENZYME REPLACEMENT THERAPY; STEM-CELL TRANSPLANTATION; DIAGNOSTIC
IMPLICATIONS; INTERMEDIATE PHENOTYPE; MUTANT ALLELES; FABRY DISEASE;
GLUCOCEREBROSIDASE; MUTATION; SEIZURES; GENOTYPE
AB Gaucher disease, the inherited deficiency of the enzyme glucocerebrosidase, is the most common of the lysosomal storage disorders. Type 2 Gaucher disease, the most severe and progressive form, manifests either prenatally or in the first months of life, followed by death within the first years of life. The rarity of the many lysosomal storage disorders makes their diagnosis a challenge, especially in the newborn period when the focus is often on more prevalent illnesses. Thus, a heightened awareness of the presentation of these rare diseases is necessary to ensure their timely consideration. This review, designed to serve as a guide to physicians treating newborns and infants with Gaucher disease, discusses the presenting manifestations of Type 2 Gaucher disease, the diagnostic work-up, associated genotypes and suggestions for management. We also address the ethical concerns that may arise with this progressive and lethal disorder, since currently available treatments may prolong life, but do not impact the neurological manifestations of the disease. Published by Elsevier Inc.
C1 [Weiss, Karin; Gonzalez, Ashley N.; Lopez, Grisel; Pedoeim, Leah; Groden, Catherine; Sidransky, Ellen] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA.
RP Sidransky, E (reprint author), NHGRI, Med Genet Branch, NIH, Room 1E623,35 Convent Dr, Bethesda, MD 20892 USA.
EM sidranse@mail.nih.gov
FU Intramural NIH HHS [ZIA MH*00002-08]
NR 85
TC 10
Z9 10
U1 0
U2 6
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1096-7192
EI 1096-7206
J9 MOL GENET METAB
JI Mol. Genet. Metab.
PD FEB
PY 2015
VL 114
IS 2
BP 110
EP 122
DI 10.1016/j.ymgme.2014.11.008
PG 13
WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research &
Experimental
SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental
Medicine
GA CA5UK
UT WOS:000348973100296
PM 25435509
ER
PT J
AU Borger, DK
Aflaki, E
Moaven, N
Lopez, G
Chae, JJ
Maniwang, E
Sidransky, E
AF Borger, Daniel K.
Aflaki, Elma
Moaven, Nima
Lopez, Grisel
Chae, Jae Jin
Maniwang, Emerson
Sidransky, Ellen
TI Impaired autophagy leads to inflammasome activation and a heightened
inflammatory profile of macrophages in Gaucher disease
SO MOLECULAR GENETICS AND METABOLISM
LA English
DT Meeting Abstract
CT 11th Annual WORLD Symposium of the Lysosomal-Disease-Network
CY FEB 09-13, 2015
CL Orlando, FL
SP Lysosomal Dis Network
C1 [Borger, Daniel K.; Aflaki, Elma; Moaven, Nima; Lopez, Grisel; Chae, Jae Jin; Maniwang, Emerson; Sidransky, Ellen] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1096-7192
EI 1096-7206
J9 MOL GENET METAB
JI Mol. Genet. Metab.
PD FEB
PY 2015
VL 114
IS 2
MA 33
BP S24
EP S24
DI 10.1016/j.ymgme.2014.12.035
PG 1
WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research &
Experimental
SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental
Medicine
GA CA5UK
UT WOS:000348973100033
ER
PT J
AU Choi, EY
Baker, E
Kaler, SG
AF Choi, Eun-Young
Baker, Eva
Kaler, Stephen G.
TI Choroid plexus-directed viral gene therapy for alpha-mannosidosis, a
prototypical lysosomal disease
SO MOLECULAR GENETICS AND METABOLISM
LA English
DT Meeting Abstract
CT 11th Annual WORLD Symposium of the Lysosomal-Disease-Network
CY FEB 09-13, 2015
CL Orlando, FL
SP Lysosomal Dis Network
C1 [Choi, Eun-Young; Kaler, Stephen G.] NICHD, NIH, Bethesda, MD USA.
[Baker, Eva] NIH, Ctr Clin, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 4
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1096-7192
EI 1096-7206
J9 MOL GENET METAB
JI Mol. Genet. Metab.
PD FEB
PY 2015
VL 114
IS 2
MA 50
BP S31
EP S31
DI 10.1016/j.ymgme.2014.12.052
PG 1
WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research &
Experimental
SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental
Medicine
GA CA5UK
UT WOS:000348973100050
ER
PT J
AU Dai, S
Dulcey, AE
Swaroop, M
Marugan, J
Mckew, J
Zheng, W
AF Dai, Sheng
Dulcey, Andres E.
Swaroop, Manju
Marugan, Juan
Mckew, John
Zheng, Wei
TI Rapid kinetics of beta-cyclodextrin entering and exiting cells:
Implication of its mechanism on reduction of cholesterol accumulation in
Niemann-Pick disease type C cells
SO MOLECULAR GENETICS AND METABOLISM
LA English
DT Meeting Abstract
CT 11th Annual WORLD Symposium of the Lysosomal-Disease-Network
CY FEB 09-13, 2015
CL Orlando, FL
SP Lysosomal Dis Network
C1 [Dai, Sheng; Dulcey, Andres E.; Swaroop, Manju; Marugan, Juan; Mckew, John; Zheng, Wei] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 2
U2 10
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1096-7192
EI 1096-7206
J9 MOL GENET METAB
JI Mol. Genet. Metab.
PD FEB
PY 2015
VL 114
IS 2
MA 59
BP S35
EP S35
DI 10.1016/j.ymgme.2014.12.061
PG 1
WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research &
Experimental
SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental
Medicine
GA CA5UK
UT WOS:000348973100059
ER
PT J
AU Gonzalez, AN
Trivedi, NS
Berhe, B
Tayebi, N
Sidransky, E
AF Gonzalez, Ashley N.
Trivedi, Niraj S.
Berhe, Bahafta
Tayebi, Nahid
Sidransky, Ellen
TI Modeling the association between Gaucher disease and Parkinson disease
using in vivo mouse models
SO MOLECULAR GENETICS AND METABOLISM
LA English
DT Meeting Abstract
CT 11th Annual WORLD Symposium of the Lysosomal-Disease-Network
CY FEB 09-13, 2015
CL Orlando, FL
SP Lysosomal Dis Network
C1 [Gonzalez, Ashley N.; Trivedi, Niraj S.; Berhe, Bahafta; Tayebi, Nahid; Sidransky, Ellen] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1096-7192
EI 1096-7206
J9 MOL GENET METAB
JI Mol. Genet. Metab.
PD FEB
PY 2015
VL 114
IS 2
MA 93
BP S48
EP S49
DI 10.1016/j.ymgme.2014.12.095
PG 2
WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research &
Experimental
SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental
Medicine
GA CA5UK
UT WOS:000348973100092
ER
PT J
AU Kim, J
Cintron, D
Groden, C
Wiggs, E
Davis, J
Mistry, P
Pastores, G
Zimran, A
Goker-Alpan, O
Sidransky, E
Lopez, G
AF Kim, Jenny
Cintron, Dahima
Groden, Catherine
Wiggs, Edythe
Davis, Joie
Mistry, Pramod
Pastores, Gregory
Zimran, Ari
Goker-Alpan, Ozlem
Sidransky, Ellen
Lopez, Grisel
TI Gaucher disease and Parldnsonism: Clinical course and prognosis
SO MOLECULAR GENETICS AND METABOLISM
LA English
DT Meeting Abstract
CT 11th Annual WORLD Symposium of the Lysosomal-Disease-Network
CY FEB 09-13, 2015
CL Orlando, FL
SP Lysosomal Dis Network
C1 [Kim, Jenny; Groden, Catherine; Wiggs, Edythe; Davis, Joie; Sidransky, Ellen; Lopez, Grisel] NIH, Bethesda, MD 20892 USA.
[Cintron, Dahima] Univ Puerto Rico, San Juan, PR 00936 USA.
[Mistry, Pramod] Yale Univ, Sch Med, New Haven, CT USA.
[Pastores, Gregory] Mater Misericordiae Univ Hosp, Natl Ctr Inherited Metab Disorders, Dublin, Ireland.
[Zimran, Ari] Shaare Zedek Med Ctr, Gaucher Clin, Jerusalem, Israel.
[Goker-Alpan, Ozlem] O&O Alpan LLC, Lysosomal Disorders Res & Treatment Unit, Fairfax, VA USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1096-7192
EI 1096-7206
J9 MOL GENET METAB
JI Mol. Genet. Metab.
PD FEB
PY 2015
VL 114
IS 2
MA 127
BP S62
EP S62
DI 10.1016/j.ymgme.2014.12.130
PG 1
WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research &
Experimental
SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental
Medicine
GA CA5UK
UT WOS:000348973100126
ER
PT J
AU Li, LS
Lim, JA
Raben, N
AF Li, Lishu
Lim, Jeong-A
Raben, Nina
TI Two masters of lysosomal and autophagosomal biogenesis, TFEB and TFE3,
and their potential therapeutic value in Pompe disease
SO MOLECULAR GENETICS AND METABOLISM
LA English
DT Meeting Abstract
CT 11th Annual WORLD Symposium of the Lysosomal-Disease-Network
CY FEB 09-13, 2015
CL Orlando, FL
SP Lysosomal Dis Network
C1 [Li, Lishu; Lim, Jeong-A; Raben, Nina] NIAMS, NIH, Bethesda, MD USA.
RI Li, Lishu /J-3191-2015
NR 0
TC 0
Z9 0
U1 0
U2 4
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1096-7192
EI 1096-7206
J9 MOL GENET METAB
JI Mol. Genet. Metab.
PD FEB
PY 2015
VL 114
IS 2
MA 152
BP S72
EP S72
DI 10.1016/j.ymgme.2014.12.155
PG 1
WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research &
Experimental
SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental
Medicine
GA CA5UK
UT WOS:000348973100151
ER
PT J
AU Long, Y
Xu, M
Shi, ZD
Swaroop, M
Xu, BY
Dai, S
Mckew, J
Zheng, W
AF Long, Yan
Xu, Miao
Shi, Zhen-Dan
Swaroop, Manju
Xu, Biying
Dai, Sheng
McKew, John
Zheng, Wei
TI Cellular distribution and mechanism of delta-tocopherol on reduction of
lysosomal cholesterol accumulation in cells with Niemann-Pick disease
type C
SO MOLECULAR GENETICS AND METABOLISM
LA English
DT Meeting Abstract
CT 11th Annual WORLD Symposium of the Lysosomal-Disease-Network
CY FEB 09-13, 2015
CL Orlando, FL
SP Lysosomal Dis Network
C1 [Long, Yan; Xu, Miao; Swaroop, Manju; Dai, Sheng; McKew, John; Zheng, Wei] NIH, Natl Ctr Adv Translat Sci, Rockville, MD USA.
[Shi, Zhen-Dan; Xu, Biying] NHLBI, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 3
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1096-7192
EI 1096-7206
J9 MOL GENET METAB
JI Mol. Genet. Metab.
PD FEB
PY 2015
VL 114
IS 2
MA 158
BP S75
EP S75
DI 10.1016/j.ymgme.2014.12.161
PG 1
WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research &
Experimental
SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental
Medicine
GA CA5UK
UT WOS:000348973100157
ER
PT J
AU Nguyen, M
Westbroek, W
Burnett, R
Fujiwara, H
Sidhu, R
Berhe, B
Tayebi, N
Aflaki, E
Ory, D
Sidransky, E
AF Nguyen, Matthew
Westbroek, Wendy
Burnett, Robert
Fujiwara, Hideji
Sidhu, Rohini
Berhe, Bahafta
Tayebi, Nahid
Aflaki, Elma
Ory, Daniel
Sidransky, Ellen
TI Development of a novel neuronal cell model for investigating the link
between glucocerebrosidase and Parkinson disease
SO MOLECULAR GENETICS AND METABOLISM
LA English
DT Meeting Abstract
CT 11th Annual WORLD Symposium of the Lysosomal-Disease-Network
CY FEB 09-13, 2015
CL Orlando, FL
SP Lysosomal Dis Network
C1 [Nguyen, Matthew; Westbroek, Wendy; Burnett, Robert; Berhe, Bahafta; Tayebi, Nahid; Aflaki, Elma; Sidransky, Ellen] NIH, Bethesda, MD 20892 USA.
[Fujiwara, Hideji; Sidhu, Rohini; Ory, Daniel] Washington Univ, St Louis, MO USA.
RI Sidhu, Rohini/G-3547-2012
NR 0
TC 0
Z9 0
U1 0
U2 3
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1096-7192
EI 1096-7206
J9 MOL GENET METAB
JI Mol. Genet. Metab.
PD FEB
PY 2015
VL 114
IS 2
MA 190
BP S87
EP S87
DI 10.1016/j.ymgme.2014.12.193
PG 1
WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research &
Experimental
SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental
Medicine
GA CA5UK
UT WOS:000348973100189
ER
PT J
AU Schiffmann, R
Swift, C
Wang, X
Brady, RO
Ries, M
AF Schiffmann, Raphael
Swift, Caren
Wang, Xuan
Brady, Roscoe O.
Ries, Markus
TI A prospective 10 year study of individualized, intensified enzyme
replacement therapy in advanced Fabry disease
SO MOLECULAR GENETICS AND METABOLISM
LA English
DT Meeting Abstract
CT 11th Annual WORLD Symposium of the Lysosomal-Disease-Network
CY FEB 09-13, 2015
CL Orlando, FL
SP Lysosomal Dis Network
C1 [Schiffmann, Raphael; Swift, Caren; Wang, Xuan] Baylor Res Inst, Dallas, TX USA.
[Brady, Roscoe O.] NINDS, Bethesda, MD 20892 USA.
[Ries, Markus] Univ Heidelberg Hosp, Heidelberg, Germany.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1096-7192
EI 1096-7206
J9 MOL GENET METAB
JI Mol. Genet. Metab.
PD FEB
PY 2015
VL 114
IS 2
MA 229
BP S103
EP S103
DI 10.1016/j.ymgme.2014.12.232
PG 1
WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research &
Experimental
SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental
Medicine
GA CA5UK
UT WOS:000348973100228
ER
PT J
AU Samuel, M
Rodriguez-Oroz, M
Antonini, A
Brotchie, JM
Chaudhuri, KR
Brown, RG
Galpern, WR
Nirenberg, MJ
Okun, MS
Lang, AE
AF Samuel, Michael
Rodriguez-Oroz, Maria
Antonini, Angelo
Brotchie, Jonathan M.
Chaudhuri, Kallol Ray
Brown, Richard G.
Galpern, Wendy R.
Nirenberg, Melissa J.
Okun, Michael S.
Lang, Anthony E.
TI Management of Impulse Control Disorders in Parkinson's Disease:
Controversies and Future Approaches
SO MOVEMENT DISORDERS
LA English
DT Review
DE Parkinson's; Impulse control; Management; Dopamine Agonist Withdrawal;
Deep Brain Stimulation; Clinical Trials
ID DEEP-BRAIN-STIMULATION; SUBTHALAMIC NUCLEUS STIMULATION; AGONIST
WITHDRAWAL SYNDROME; DOPAMINE DYSREGULATION SYNDROME;
1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE-LESIONED MACAQUE MODEL;
COGNITIVE-BEHAVIORAL THERAPY; REACTION-TIME-TASK; COMPULSIVE BEHAVIORS;
RECEPTOR ANTAGONIST; INDUCED DYSKINESIA
AB Impulse control disorders in Parkinson's disease are a group of impulsive behaviors most often associated with dopaminergic treatment. Presently, there is a lack of high quality evidence available to guide their management. This manuscript reviews current management strategies, before concentrating on the concept of dopamine agonist withdrawal syndrome and its implications for the management of impulse control disorders. Further, we focus on controversies, including the role of more recently available anti-parkinsonian drugs, and potential future approaches involving routes of drug delivery, nonpharmacological treatments (such as cognitive behavioral therapy and deep brain stimulation), and other as yet experimental strategies. (c) 2015 International Parkinson and Movement Disorder Society
C1 [Samuel, Michael; Chaudhuri, Kallol Ray] Kings Hlth Partners, Kings Coll Hosp, Natl Parkinson Fdn Int Ctr Excellence, Dept Neurol, London, England.
[Rodriguez-Oroz, Maria] Univ Hosp Donostia, Dept Neurol, San Sebastian, Spain.
[Rodriguez-Oroz, Maria] BioDonostia Res Inst, Neurosci Unit, San Sebastian, Spain.
[Rodriguez-Oroz, Maria] Ikerbasque, Basque Fdn Sci, E-48011 Bilbao, Spain.
[Rodriguez-Oroz, Maria] Ctr Invest Biomed Red Enfermedades Neurodegenerat, Barcelona, Spain.
[Antonini, Angelo] Fdn Osped San Camillo IRCCS, Parkinson Unit, Venice, Italy.
[Brotchie, Jonathan M.] Toronto Western Hosp, Toronto Western Res Inst, Toronto, ON M5T 2S8, Canada.
[Chaudhuri, Kallol Ray] Kings Coll London, Inst Psychiat, Dept Clin Neurosci, London SE5 8AF, England.
[Brown, Richard G.] Kings Coll London, Inst Psychiat, Dept Psychol PO77, London SE5 8AF, England.
[Galpern, Wendy R.] NINDS, NIH, Bethesda, MD 20892 USA.
[Nirenberg, Melissa J.] NYU, Dept Neurol, Sch Med, New York, NY 10016 USA.
[Okun, Michael S.] UF Ctr Movement Disorders & Neurorestorat, Gainesville, FL 32607 USA.
[Lang, Anthony E.] Toronto Western Hosp, Morton & Gloria Movement Disorders Clin, Toronto, ON M5T 2S8, Canada.
[Lang, Anthony E.] Toronto Western Hosp, Edmond J Safra Program Parkinsons Dis, Toronto, ON M5T 2S8, Canada.
RP Samuel, M (reprint author), Kings Hlth Partners, Kings Coll Hosp, Natl Parkinson Fdn Int Ctr Excellence, Dept Neurol, London, England.
EM m.samuel@nhs.net
RI Brown, Richard/A-9599-2010;
OI Brown, Richard/0000-0001-9021-0172; Ray Chaudhuri, K/0000-0003-2815-0505
FU Movement Disorders Society (USA); National Institute of Health (USA)
[U13NS080495]; Parkinson's Disease Foundation (USA); Parkinson's UK;
Parkinson's Disease Society (Canada); AbbVie Ltd; UCB; St Jude Medical
Limited
FX The ICD meeting in Boston October 25-26, 2012 was sponsored by the
Movement Disorders Society (USA), and received financial support from
the Movement Disorders Society (USA), National Institute of Health (USA,
U13NS080495), Parkinson's Disease Foundation (USA), Parkinson's UK,
Parkinson's Disease Society (Canada), AbbVie Ltd, UCB, and St Jude
Medical Limited.
NR 95
TC 16
Z9 17
U1 4
U2 15
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0885-3185
EI 1531-8257
J9 MOVEMENT DISORD
JI Mov. Disord.
PD FEB
PY 2015
VL 30
IS 2
BP 150
EP 159
DI 10.1002/mds.26099
PG 10
WC Clinical Neurology
SC Neurosciences & Neurology
GA CB0IZ
UT WOS:000349310600004
PM 25607799
ER
PT J
AU Hallett, M
Obeso, J
AF Hallett, Mark
Obeso, Jose
TI Where Does Chorea Come From? Cortical Excitability Findings Challenge
Classic Pathophysiological Concepts
SO MOVEMENT DISORDERS
LA English
DT Editorial Material
ID BASAL GANGLIA DISORDERS; PARKINSONS-DISEASE; HUNTINGTONS-DISEASE;
MOVEMENT-DISORDERS; PRIMATE MODELS; STIMULATION
C1 [Hallett, Mark] NINDS, Bethesda, MD 20892 USA.
[Obeso, Jose] Hosp Madrid, CINAC, Madrid, Spain.
[Obeso, Jose] CEU San Pablo Univ, Madrid, Spain.
RP Hallett, M (reprint author), NINDS, Human Motor Control Sect, NIH, Bldg 10,Room 7D37,10 Ctr Dr, Bethesda, MD 20892 USA.
EM hallettm@ninds.nih.gov
FU Intramural NIH HHS
NR 16
TC 2
Z9 2
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0885-3185
EI 1531-8257
J9 MOVEMENT DISORD
JI Mov. Disord.
PD FEB
PY 2015
VL 30
IS 2
BP 169
EP 170
DI 10.1002/mds.26109
PG 2
WC Clinical Neurology
SC Neurosciences & Neurology
GA CB0IZ
UT WOS:000349310600007
PM 25546440
ER
PT J
AU Singleton, A
AF Singleton, Andrew
TI X-Linked Parkinson's Disease
SO MOVEMENT DISORDERS
LA English
DT Editorial Material
C1 NIA, Bethesda, MD 20892 USA.
RP Singleton, A (reprint author), NIA, Bethesda, MD 20892 USA.
RI Singleton, Andrew/C-3010-2009
NR 1
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0885-3185
EI 1531-8257
J9 MOVEMENT DISORD
JI Mov. Disord.
PD FEB
PY 2015
VL 30
IS 2
BP 196
EP 196
DI 10.1002/mds.26131
PG 1
WC Clinical Neurology
SC Neurosciences & Neurology
GA CB0IZ
UT WOS:000349310600011
PM 25641059
ER
PT J
AU Johnson, JO
Stevanin, G
van de Leemput, J
Hernandez, DG
Arepalli, S
Forlani, S
Zonozi, R
Gibbs, JR
Brice, A
Durr, A
Singleton, AB
AF Johnson, Janel O.
Stevanin, Giovanni
van de Leemput, Joyce
Hernandez, Dena G.
Arepalli, Sampath
Forlani, Sylvie
Zonozi, Reza
Gibbs, J. Raphael
Brice, Alexis
Durr, Alexandra
Singleton, Andrew B.
TI A 7.5-Mb Duplication at Chromosome 11q21-11q22.3 Is Associated With a
Novel Spastic Ataxia Syndrome
SO MOVEMENT DISORDERS
LA English
DT Article
DE whole-genome genotyping; genomic duplications; spinocerebellar ataxia;
structural variation; SCA39
ID COPY NUMBER VARIATION; SPINOCEREBELLAR ATAXIA; DISEASE
AB BackgroundThe autosomal dominant spinocerebellar ataxias are most commonly caused by nucleotide repeat expansions followed by base-pair changes in functionally important genes. Structural variation has recently been shown to underlie spinocerebellar ataxia types 15 and 20.
MethodsWe applied single-nucleotide polymorphism (SNP) genotyping to determine whether structural variation causes spinocerebellar ataxia in a family from France.
ResultsWe identified an approximately 7.5-megabasepair duplication on chromosome 11q21-11q22.3 that segregates with disease. This duplication contains an estimated 44 genes. Duplications at this locus were not found in control individuals.
ConclusionsWe have identified a new spastic ataxia syndrome caused by a genomic duplication, which we have denoted as spinocerebellar ataxia type 39. Finding additional families with this phenotype will be important to identify the genetic lesion underlying disease. (c) 2014 International Parkinson and Movement Disorder Society
C1 [Johnson, Janel O.; van de Leemput, Joyce; Hernandez, Dena G.; Arepalli, Sampath; Zonozi, Reza; Gibbs, J. Raphael; Singleton, Andrew B.] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
[Johnson, Janel O.; van de Leemput, Joyce; Hernandez, Dena G.; Gibbs, J. Raphael] UCL, Inst Neurol, Dept Mol Neurosci, London, England.
[Johnson, Janel O.; van de Leemput, Joyce; Hernandez, Dena G.; Gibbs, J. Raphael] UCL, Inst Neurol, Reta Lila Weston Inst Neurol Studies, London, England.
[Stevanin, Giovanni; Forlani, Sylvie; Brice, Alexis; Durr, Alexandra] INSERM, U1127, Paris, France.
[Stevanin, Giovanni; Forlani, Sylvie; Brice, Alexis; Durr, Alexandra] Univ Paris 06, Sorbonne Univ, Inst Cerveau & Moelle Epiniere, UMR S1127, Paris, France.
[Stevanin, Giovanni; Forlani, Sylvie; Brice, Alexis; Durr, Alexandra] CNRS, UMR7225, Paris, France.
[Stevanin, Giovanni] Ecole Prat Hautes Etud, Paris, France.
RP Singleton, AB (reprint author), 9000 Rockville Pike Bldg 35 Rm1A1000, Bethesda, MD 20892 USA.
EM singleta@mail.nih.gov
RI Singleton, Andrew/C-3010-2009; Stevanin, Giovanni/E-5038-2016;
OI Stevanin, Giovanni/0000-0001-9368-8657
FU National Institute on Aging, National Institutes of Health, Department
of Health and Human Services; European Union; Verum foundation;
association Connaitre les Syndromes cerebelleux (France); Programme
Hospitalier de Recherche Clinique
FX This study was supported by the National Institute on Aging, National
Institutes of Health, Department of Health and Human Services, in part
by the European Union (to the The NEUROMICS Consortium Network), the
Verum foundation, the association Connaitre les Syndromes cerebelleux
(France) and the Programme Hospitalier de Recherche Clinique (to A.D.)
NR 15
TC 1
Z9 1
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0885-3185
EI 1531-8257
J9 MOVEMENT DISORD
JI Mov. Disord.
PD FEB
PY 2015
VL 30
IS 2
BP 262
EP 266
DI 10.1002/mds.26059
PG 5
WC Clinical Neurology
SC Neurosciences & Neurology
GA CB0IZ
UT WOS:000349310600022
PM 25545641
ER
PT J
AU Catalfamo, M
Mawle, A
Verthelyi, D
AF Catalfamo, Marta
Mawle, Alison
Verthelyi, Daniela
TI Immunology careers at the NIH, FDA and CDC: different paths that focus
on advancing public health
SO NATURE IMMUNOLOGY
LA English
DT Article
C1 [Catalfamo, Marta] NIAID, Immunoregulat Lab, US NIH, Bethesda, MD 20892 USA.
[Mawle, Alison] Ctr Dis Control & Prevent, Natl Ctr Immunizat & Resp Dis, Atlanta, GA USA.
[Verthelyi, Daniela] US FDA, Ctr Drug Evaluat & Res, Off Biotechnol Prod, Div Therapeut Prot, Silver Spring, MD USA.
RP Catalfamo, M (reprint author), NIAID, Immunoregulat Lab, US NIH, Bldg 10, Bethesda, MD 20892 USA.
EM catalfam@mail.nih.gov
NR 9
TC 1
Z9 1
U1 0
U2 3
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1529-2908
EI 1529-2916
J9 NAT IMMUNOL
JI Nat. Immunol.
PD FEB
PY 2015
VL 16
IS 2
BP 129
EP 132
PG 4
WC Immunology
SC Immunology
GA AZ3QZ
UT WOS:000348143100001
PM 25594454
ER
PT J
AU Huang, YF
Guo, LY
Qiu, J
Chen, X
Hu-Li, J
Siebenlist, U
Williamson, PR
Urban, JF
Paul, WE
AF Huang, Yuefeng
Guo, Liying
Qiu, Jin
Chen, Xi
Hu-Li, Jane
Siebenlist, Ulrich
Williamson, Peter R.
Urban, Joseph F.
Paul, William E.
TI IL-25-responsive, lineage-negative KLRG1(hi) cells are multipotential
'inflammatory' type 2 innate lymphoid cells
SO NATURE IMMUNOLOGY
LA English
DT Article
ID TRANSCRIPTION FACTOR GATA3; LUNG INFLAMMATION; IMMUNITY; T(H)2;
HOMEOSTASIS; POPULATION; INFECTION; ELICITS; IL-25; FATE
AB Innate lymphoid cells (ILCs) are lymphocyte-like cells that lack T cell or B cell antigen receptors and mediate protective and repair functions through cytokine secretion. Among these, type 2 ILCs (ILC2 cells) are able to produce type 2 cytokines. We report the existence of an inflammatory ILC2 (iILC2) population responsive to interleukin 25 (IL-25) that complemented IL-33-responsive natural ILC2 (nILC2) cells. iILC2 cells developed into nILC2-like cells in vitro and in vivo and contributed to the expulsion of Nippostrongylus brasiliensis. They also acquired IL-17-producing ability and provided partial protection against Candida albicans. We propose that iILC2 cells are transient progenitors of ILCs mobilized by inflammation and infection that develop into nILC2-like cells or ILC3-like cells and contribute to immunity to both helminths and fungi.
C1 [Huang, Yuefeng; Guo, Liying; Chen, Xi; Hu-Li, Jane; Paul, William E.] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA.
[Qiu, Jin; Williamson, Peter R.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
[Siebenlist, Ulrich] NIAID, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA.
[Urban, Joseph F.] ARS, Diet Genom & Immunol Lab, Beltsville Human Nutr Res Ctr, USDA, Beltsville, MD USA.
RP Paul, WE (reprint author), NIAID, Immunol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM wpaul@niaid.nih.gov
OI Urban, Joseph/0000-0002-1590-8869
FU NIAID Division of Intramural Research (US National Institutes of Health)
FX We thank J. Zhu for critical reading of the manuscript; J. Edwards for
assistance in the preparation of sorter-purified cells; L. Feigenbaum of
the SAIC Laboratory Animal Sciences Program for injection of the
recombinant bacterial artificial chromosome into oocytes, transfer into
pseudopregnant females and screening of pups; C. Dong (MD Anderson
Cancer Center) for IL-17F-RFP reporter mice; A. McKenzie (MRC Laboratory
of Molecular Biology, Cambridge) for Il1rl1-/- mice; and
members of Laboratory of Immunology at NIAID for discussions. Supported
by the NIAID Division of Intramural Research (US National Institutes of
Health).
NR 29
TC 64
Z9 65
U1 4
U2 17
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1529-2908
EI 1529-2916
J9 NAT IMMUNOL
JI Nat. Immunol.
PD FEB
PY 2015
VL 16
IS 2
BP 161
EP +
DI 10.1038/ni.3078
PG 10
WC Immunology
SC Immunology
GA AZ3QZ
UT WOS:000348143100008
PM 25531830
ER
PT J
AU Yu, F
Sharma, S
Edwards, J
Feigenbaum, L
Zhu, JF
AF Yu, Fang
Sharma, Suveena
Edwards, Julie
Feigenbaum, Lionel
Zhu, Jinfang
TI Dynamic expression of transcription factors T-bet and GATA-3 by
regulatory T cells maintains immunotolerance
SO NATURE IMMUNOLOGY
LA English
DT Article
ID ROR-GAMMA-T; FACTOR FOXP3; HELPER-CELLS; IN-VIVO; DIFFERENTIATION;
INFLAMMATION; ACTIVATION; RESPONSES; PROGRAM; SUPPRESSION
AB Regulatory T cells (T-reg cells) can express the transcription factors T-bet and GATA-3, but the function of this expression and whether such cells represent stable subsets is still unknown. By using various reporter tools, we found that the expression of T-bet and GATA-3 in T-reg cells was dynamically influenced by the cytokine environment. T-reg cell-specific deletion of the gene encoding either T-bet (Tbx21) or GATA-3 (Gata3) alone did not result in loss of T-reg cell function; however, mice with combined deficiency in both genes in T-reg cells developed severe autoimmune-like diseases. Loss of T-reg cell function correlated with upregulation of expression of the transcription factor ROR gamma t and reduced expression of the transcription factor Foxp3. Thus, in the steady state, activated T-reg cells transiently upregulated either T-bet or GATA-3 to maintain T cell homeostasis.
C1 [Yu, Fang; Sharma, Suveena; Edwards, Julie; Zhu, Jinfang] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA.
[Feigenbaum, Lionel] NCI, Lab Anim Sci Program, Frederick, MD 21701 USA.
RP Zhu, JF (reprint author), NIAID, Immunol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM jfzhu@niaid.nih.gov
RI Zhu, Jinfang/B-7574-2012
FU Division of Intramural Research of the NIAID (US National Institutes of
Health)
FX We thank J.D. Engel (University of Michigan) for GATA-3-GFP reporter
mice on the C57BL/6 background; S. Reiner (University of Columbia) for
Tbx21fl/fl mice; A. Rudensky (Memorial Sloan Kettering Cancer
Center) for Foxp3-IRES-YFP-Cre mice; D. Jankovic (National Institute of
Allergy and Infectious Diseases (NIAID)) for Stat1-/- mice;
E. Shevach, Y. Belkaid and W. Paul for critical reading of the
manuscript and discussions; A. Thornton for discussions; L. Guo for the
help with enzyme-linked immunosorbent assay experiments; N. Cereb and
S.Y. Yang (Histogenetics) and S. Reiner (Columbia University) for
constructing and providing Tbx21fl/fl mice; and the flow cytometry core
facility of the NIAID for cell sorting. Supported by the Division of
Intramural Research of the NIAID (US National Institutes of Health).
NR 46
TC 36
Z9 37
U1 5
U2 14
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1529-2908
EI 1529-2916
J9 NAT IMMUNOL
JI Nat. Immunol.
PD FEB
PY 2015
VL 16
IS 2
BP 197
EP +
DI 10.1038/ni.3053
PG 12
WC Immunology
SC Immunology
GA AZ3QZ
UT WOS:000348143100012
PM 25501630
ER
PT J
AU Dalton, HJ
Garcia-Filion, P
Holubkov, R
Moler, FW
Shanley, T
Heidemann, S
Meert, K
Berg, RA
Berger, J
Carcillo, J
Newth, C
Harrison, R
Doctor, A
Rycus, P
Dean, JM
Jenkins, T
Nicholson, C
AF Dalton, Heidi J.
Garcia-Filion, Pamela
Holubkov, Richard
Moler, Frank W.
Shanley, Thomas
Heidemann, Sabrina
Meert, Kathleen
Berg, Robert A.
Berger, John
Carcillo, Joseph
Newth, Christopher
Harrison, Richard
Doctor, Allan
Rycus, Peter
Dean, J. Michael
Jenkins, Tammara
Nicholson, Carol
CA Eunice Kennedy Shriver Natl Inst
TI Association of Bleeding and Thrombosis With Outcome in Extracorporeal
Life Support
SO PEDIATRIC CRITICAL CARE MEDICINE
LA English
DT Article
DE bleeding; cardiopulmonary bypass; complications; extracorporeal life
support; extracorporeal membrane oxygenation; thrombosis
ID CONGENITAL DIAPHRAGMATIC-HERNIA; MEMBRANE-OXYGENATION;
CARDIOPULMONARY-RESUSCITATION; ORGANIZATION REGISTRY; CARDIAC-ARREST;
ECMO; CHILDREN; SURVIVAL; FAILURE; ANTICOAGULATION
AB Objective: Changes in technology and increased reports of successful extracorporeal life support use in patient populations, such as influenza, cardiac arrest, and adults, are leading to expansion of extracorporeal life support. Major limitations to extracorporeal life support expansion remain bleeding and thrombosis. These complications are the most frequent causes of death and morbidity. As a pilot project to provide baseline data for a detailed evaluation of bleeding and thrombosis in the current era, extracorporeal life support patients were analyzed from eight centers in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Collaborative Pediatric Critical Care Research Network.
Study Design: Retrospective analysis of patients (< 19 yr) reported to the Extracorporeal Life Support Organization registry from eight Collaborative Pediatric Critical Care Research Network centers between 2005 and 2011.
Setting: Tertiary children's hospitals within the Collaborative Pediatric Critical Care Research Network.
Subjects: The study cohort consisted of 2,036 patients (13% with congenital diaphragmatic hernia).
Interventions: None.
Main Results: In the cohort of patients without congenital diaphragmatic hernia (n = 1,773), bleeding occurred in 38% of patients, whereas thrombosis was noted in 31%. Bleeding and thrombosis were associated with a decreased survival by 40% (relative risk, 0.59; 95% CI, 0.53-0.66) and 33% (odds ratio, 0.67; 95% CI, 0.60-0.74). Longer duration of extracorporeal life support and use of venoarterial cannulation were also associated with increased risk of bleeding and/or thrombotic complications and lower survival. The most common bleeding events included surgical site bleeding (17%; n = 306), cannulation site bleeding (14%; n = 256), and intracranial hemorrhage (11%; n = 192). Common thrombotic events were clots in the circuit (15%; n = 274) and the oxygenator (12%; n = 212) and hemolysis (plasma-free hemoglobin > 50 mg/dL) (10%; n = 177). Among patients with congenital diaphragmatic hernia, bleeding and thrombosis occurred in, respectively, 45% (n = 118) and 60% (n = 159), Bleeding events were associated with reduced survival (relative risk, 0.62; 95% CI, 0.46-0.86) although thrombotic events were not (relative risk, 0.92; 95% CI, 0.67-1.26).
Conclusions: Bleeding and thrombosis remain common complications in patients undergoing extracorporeal life support. Further research to reduce or eliminate bleeding and thrombosis is indicated to help improve patient outcome.
C1 [Dalton, Heidi J.] Phoenix Childrens Hosp, Dept Child Hlth, Phoenix, AZ 85006 USA.
[Dalton, Heidi J.] Univ Arizona, Coll Med Phoenix, Phoenix, AZ USA.
[Garcia-Filion, Pamela] Phoenix Childrens Hosp, Phoenix, AZ USA.
[Holubkov, Richard; Dean, J. Michael] Univ Utah, Sch Med, Dept Pediat, Salt Lake City, UT USA.
[Moler, Frank W.; Shanley, Thomas] Univ Michigan, Dept Pediat, Ann Arbor, MI 48109 USA.
[Heidemann, Sabrina; Meert, Kathleen] Childrens Hosp Michigan, Dept Pediat, Detroit, MI 48201 USA.
[Berg, Robert A.] Childrens Hosp Philadelphia, Dept Pediat, Philadelphia, PA 19104 USA.
[Berger, John] Childrens Natl Med Ctr, Dept Pediat, Washington, DC 20010 USA.
[Carcillo, Joseph] Childrens Hosp Pittsburgh, Dept Crit Care & Anesthesia, Pittsburgh, PA 15213 USA.
[Newth, Christopher] Childrens Hosp Los Angeles, Dept Anesthesiol & Crit Care Med, Los Angeles, CA 90027 USA.
[Harrison, Richard] Univ Calif Los Angeles, Dept Pediat, Los Angeles, CA 90024 USA.
[Doctor, Allan] Washington Univ, Sch Med, Dept Pediat, St Louis Childrens Hosp, St Louis, MO 63110 USA.
[Doctor, Allan] Washington Univ, Sch Med, Dept Biochem, St Louis Childrens Hosp, St Louis, MO 63110 USA.
[Rycus, Peter] Extracorporeal Life Support Org, Ann Arbor, MI USA.
[Jenkins, Tammara; Nicholson, Carol] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pediat Trauma & Crit Illness Branch, NIH, Bethesda, MD USA.
RP Dalton, HJ (reprint author), Phoenix Childrens Hosp, Dept Child Hlth, Phoenix, AZ 85006 USA.
EM heidi.dalton26@gmail.com
OI Doctor, Allan/0000-0002-6096-6400
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development, National Institutes of Health, Department of Health and
Human Services [U10HD050096, U10HD049981, U10HD049983, U10HD050012,
U10HD063108, U10HD063106, U10HD063114, U01HD049934]; National Institutes
of Health (NIH); Eunice Kennedy Shriver National Institute of Child
Health and Human Development, NIH, Department of Health and Human
Services [U10HD050096, U10HD049981, U10HD049983, U10HD050012,
U10HD063108, U10HD063106, U10HD063114, U01HD049934]; NICHD; NIH; NIH
CPCCRN; NICHD CPCCRN; NICHD/NIH; Collaborative Pediatric Critical Care
Research Network; CPCCRN
FX Supported, in part, by the following cooperative agreements from the
Eunice Kennedy Shriver National Institute of Child Health and Human
Development, National Institutes of Health, Department of Health and
Human Services: U10HD050096, U10HD049981, U10HD049983, U10HD050012,
U10HD063108, U10HD063106, U10HD063114, and U01HD049934.; Dr. Dalton
received royalties from the Rogers Textbook of Critical Care Medicine
and received support for article research from the National Institutes
of Health (NIH). Her institution received grant support: this work was
supported, in part, by the following cooperative agreements from the
Eunice Kennedy Shriver National Institute of Child Health and Human
Development, NIH, Department of Health and Human Services: U10HD050096,
U10HD049981, U10HD049983, U10HD050012, U10HD063108, U10HD063106,
U10HD063114, and U01HD049934 (centers who participated in this project
were those in the Collaborative Pediatric Critical Care Research
Network); consulted for rEVO Biologics; and lectured for rEVO Biologics.
Dr. Garcia-Filion's institution received grant support from the NICHD
(paid under the grant for the Collaborative Pediatric Critical Care
Research Network [CPCCRN]). Dr. Holubkov served as a board member for
Pfizer Inc. (Data Safety Monitoring Board), consulted for St. Jude
Medical Inc. (biostatistical consultation), and received support for
article research from the NIH. Dr. Holubkov and his institution received
grant support from the NIH CPCCRN (coordinating center funding for
CPCCRN). Dr. Moler received support for article research from the NIH.
Dr. Shanley consulted for Case Western Res University (EAB Member),
received royalties from Springer (Springer for text book editing),
received support for travel from SPR (secretary-treasurer for SPR), and
received support for article research from the NIH. His institution
received grant support from the NIH (CPCCRN funding and NIH grants) and
received support for travel from the NIH (CPCCRN Funding). Dr. Heidemann
received support for article research from the NIH. Her institution
received grant support and support for travel. Dr. Meert received
support for article research from the NIH. Her institution received
grant support from the NIH. Dr. Berg received support for article
research from the NIH. His institution received grant support (This
study was funded by the NICHD CPCCRN grant. Dr. Berg is a PI on the
grant) and received support for travel (travel to CPCCRN meetings to
discuss this study funded by NICHD CPCCRN grant). Dr. Berger received
support for article research from NIH. His institution received grant
support from the NICHD/NIH. Dr. Carcillo received support for article
research from the NIH. His institution received grant support and
support for travel. Dr. Newth received support for article research from
the NIH. His institution received grant support from the NICHD and the
Collaborative Pediatric Critical Care Research Network. Dr. Harrison
received support for article research from the NIH. His institution
received grant support and support for travel from the NIH and CPCCRN.
Dr. Dean received support for article research from the NIH. His
institution received grant support from the NIH. Dr. Jenkins received
support for article research from the NIH and disclosed government work.
Dr. Nicholson received support for article search from the NIH and
disclosed government work. Dr. Rycus disclosed that he does not have any
potential conflicts of interest.
NR 31
TC 10
Z9 10
U1 0
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1529-7535
EI 1947-3893
J9 PEDIATR CRIT CARE ME
JI Pediatr. Crit. Care Med.
PD FEB
PY 2015
VL 16
IS 2
BP 167
EP 174
DI 10.1097/PCC.0000000000000317
PG 8
WC Critical Care Medicine; Pediatrics
SC General & Internal Medicine; Pediatrics
GA CB1KZ
UT WOS:000349387600016
PM 25647124
ER
PT J
AU Remy, KE
Chertow, DS
AF Remy, Kenneth E.
Chertow, Daniel S.
TI A Place at the Table for Children in the Ebola Virus Disease Discussion
SO PEDIATRIC CRITICAL CARE MEDICINE
LA English
DT Editorial Material
DE Ebola virus; hypovolemic shock; pediatric critical care; sepsis
ID WEST-AFRICA; SURVIVAL
C1 [Remy, Kenneth E.; Chertow, Daniel S.] NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA.
RP Remy, KE (reprint author), NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA.
OI Remy, Kenneth/0000-0001-5222-9884
NR 17
TC 1
Z9 1
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1529-7535
EI 1947-3893
J9 PEDIATR CRIT CARE ME
JI Pediatr. Crit. Care Med.
PD FEB
PY 2015
VL 16
IS 2
BP 184
EP 185
DI 10.1097/PCC.0000000000000368
PG 2
WC Critical Care Medicine; Pediatrics
SC General & Internal Medicine; Pediatrics
GA CB1KZ
UT WOS:000349387600018
PM 25647125
ER
PT J
AU Kumar, A
Baycin-Hizal, D
Shiloach, J
Bowen, MA
Betenbaugh, MJ
AF Kumar, Amit
Baycin-Hizal, Deniz
Shiloach, Joseph
Bowen, Michael A.
Betenbaugh, Michael J.
TI Coupling enrichment methods with proteomics for understanding and
treating disease
SO PROTEOMICS CLINICAL APPLICATIONS
LA English
DT Review
DE Biomarker discovery; Drug target discovery; Exosomes; Membrane
proteomics; mAb discovery
ID N-LINKED GLYCOPROTEINS; TANDEM MASS-SPECTROMETRY; REVEAL DIFFERENTIAL
EXPRESSION; PLASMA-MEMBRANE PROTEOMICS; PROTEIN REFERENCE DATABASE;
COLORECTAL-CANCER CELLS; TUMOR-DERIVED EXOSOMES; QUANTITATIVE
PROTEOMICS; EXTRACELLULAR VESICLES; CEREBROSPINAL-FLUID
AB Owing to recent advances in proteomics analytical methods and bioinformatics capabilities there is a growing trend toward using these capabilities for the development of drugs to treat human disease, including target and drug evaluation, understanding mechanisms of drug action, and biomarker discovery. Currently, the genetic sequences of many major organisms are available, which have helped greatly in characterizing proteomes in model animal systems and humans. Through proteomics, global profiles of different disease states can be characterized (e.g. changes in types and relative levels as well as changes in PTMs such as glycosylation or phosphorylation). Although intracellular proteomics can provide a broad overview of physiology of cells and tissues, it has been difficult to quantify the low abundance proteins which can be important for understanding the diseased states and treatment progression. For this reason, there is increasing interest in coupling comparative proteomics methods with subcellular fractionation and enrichment techniques for membranes, nucleus, phosphoproteome, glycoproteome as well as low abundance serum proteins. In this review, we will provide examples of where the utilization of different proteomics-coupled enrichment techniques has aided target and biomarker discovery, understanding the drug targeting mechanism, and mAb discovery. Taken together, these improvements will help to provide a better understanding of the pathophysiology of various diseases including cancer, autoimmunity, inflammation, cardiovascular disease, and neurological conditions, and in the design and development of better medicines for treating these afflictions.
C1 [Kumar, Amit; Betenbaugh, Michael J.] Johns Hopkins Univ, Dept Chem & Biomol Engn, Baltimore, MD 21218 USA.
[Kumar, Amit; Baycin-Hizal, Deniz; Bowen, Michael A.] MedImmune LLC, Antibody Discovery & Prot Engn, Gaithersburg, MD USA.
[Kumar, Amit; Shiloach, Joseph] NIDDK, Biotechnol Core Lab, NIH, Bethesda, MD 20892 USA.
RP Betenbaugh, MJ (reprint author), Johns Hopkins Univ, Dept Chem & Biomol Engn, Baltimore, MD 21218 USA.
EM beten@jhu.edu
NR 169
TC 8
Z9 8
U1 6
U2 24
PU WILEY-V C H VERLAG GMBH
PI WEINHEIM
PA POSTFACH 101161, 69451 WEINHEIM, GERMANY
SN 1862-8346
EI 1862-8354
J9 PROTEOM CLIN APPL
JI Proteom. Clin. Appl.
PD FEB
PY 2015
VL 9
IS 1-2
SI SI
BP 33
EP 47
DI 10.1002/prca.201400097
PG 15
WC Biochemical Research Methods; Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA CB2DH
UT WOS:000349436400005
PM 25523641
ER
PT J
AU Fan, W
Lam, J
Moen, P
Kelly, E
King, R
McHale, S
AF Fan, Wen
Lam, Jack
Moen, Phyllis
Kelly, Erin
King, Rosalind
McHale, Susan
TI Constrained choices ? Linking employees' and spouses' work time to
health behaviors
SO SOCIAL SCIENCE & MEDICINE
LA English
DT Article
DE US; Fast food consumption; Exercise; Work hours; Gender; Couple; Spouse;
Constrained choices
ID PHYSICAL-ACTIVITY; GENDER-DIFFERENCES; COPING STRATEGIES;
FOOD-CONSUMPTION; POPULATION; EMPLOYMENT; EXERCISE; PERSPECTIVE;
SPILLOVER; HOUSEWORK
AB There are extensive literatures on work conditions and health and on family contexts and health, but less research asking how a spouse or partners' work conditions may affect health behaviors. Drawing on the constrained choices framework, we theorized health behaviors as a product of one's own time and spouses' work time as well as gender expectations. We examined fast food consumption and exercise behaviors using survey data from 429 employees in an Information Technology (IT) division of a U.S. Fortune 500 firm and from their spouses. We found fast food consumption is affected by men's work hours-both male employees' own work hours and the hours worked by husbands of women respondents-in a nonlinear way. The groups most likely to eat fast food are men working 50 h/week and women whose husbands work 45-50 h/week. Second, exercise is better explained if work time is conceptualized at the couple, rather than individual, level. In particular, neo-traditional arrangements (where husbands work longer than their wives) constrain women's ability to engage in exercise but increase odds of men exercising. Women in couples where both partners are working long hours have the highest odds of exercise. In addition, women working long hours with high schedule control are more apt to exercise and men working long hours whose wives have high schedule flexibility are as well. Our findings suggest different health behaviors may have distinct antecedents but gendered work-family expectations shape time allocations in ways that promote men's and constrain women's health behaviors. They also suggest the need to expand the constrained choices framework to recognize that long hours may encourage exercise if both partners are looking to sustain long work hours and that work resources, specifically schedule control, of one partner may expand the choices of the other. (C) 2014 Elsevier Ltd. All rights reserved.
C1 [Fan, Wen; Lam, Jack; Moen, Phyllis; Kelly, Erin] Univ Minnesota, Minneapolis, MN 55455 USA.
[King, Rosalind] NICHHD, Bethesda, MD USA.
[McHale, Susan] Penn State Univ, University Pk, PA 16802 USA.
RP Fan, W (reprint author), Univ Minnesota, Dept Sociol, 267 19th Ave S, Minneapolis, MN 55455 USA.
EM fanxx102@umn.edu
RI Lam, Jack/B-4976-2016
OI Lam, Jack/0000-0002-7169-4930
FU NICHD NIH HHS [U01 HD051276, U01 HD051256]
NR 52
TC 4
Z9 4
U1 2
U2 7
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0277-9536
J9 SOC SCI MED
JI Soc. Sci. Med.
PD FEB
PY 2015
VL 126
BP 99
EP 109
DI 10.1016/j.socscimed.2014.12.015
PG 11
WC Public, Environmental & Occupational Health; Social Sciences, Biomedical
SC Public, Environmental & Occupational Health; Biomedical Social Sciences
GA CB2AM
UT WOS:000349429100011
PM 25531550
ER
PT J
AU Lopez, LM
Hill, WD
Harris, SE
Hernandez, MV
Maniega, SM
Bastin, ME
Bailey, E
Smith, C
McBride, M
McClure, J
Graham, D
Dominiczak, A
Yang, Q
Fornage, M
Ikram, MA
Debette, S
Launer, L
Bis, JC
Schmidt, R
Seshadri, S
Porteous, DJ
Starr, J
Deary, IJ
Wardlaw, JM
AF Lopez, Lorna M.
Hill, W. David
Harris, Sarah E.
Hernandez, Maria Valdes
Maniega, Susana Munoz
Bastin, Mark E.
Bailey, Emma
Smith, Colin
McBride, Martin
McClure, John
Graham, Delyth
Dominiczak, Anna
Yang, Qiong
Fornage, Myriam
Ikram, M. Arfan
Debette, Stephanie
Launer, Lenore
Bis, Joshua C.
Schmidt, Reinhold
Seshadri, Sudha
Porteous, David J.
Starr, John
Deary, Ian J.
Wardlaw, Joanna M.
TI Genes From a Translational Analysis Support a Multifactorial Nature of
White Matter Hyperintensities
SO STROKE
LA English
DT Article
DE genetics; humans; leukoencephalopathies; magnetic resonance imaging
ID GENOME-WIDE ASSOCIATION; ISCHEMIC-STROKE; ATAXIA-TELANGIECTASIA; LACUNAR
STROKE; RISK-FACTORS; DISEASE; BRAIN; METAANALYSIS; EXPRESSION;
PHENOTYPES
AB Background and Purpose-White matter hyperintensities (WMH) of presumed vascular origin increase the risk of stroke and dementia. Despite strong WMH heritability, few gene associations have been identified. Relevant experimental models may be informative.
Methods-We tested the associations between genes that were differentially expressed in brains of young spontaneously hypertensive stroke-prone rats and human WMH (using volume and visual score) in 621 subjects from the Lothian Birth Cohort 1936 (LBC1936). We then attempted replication in 9361 subjects from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE). We also tested the subjects from LBC1936 for previous genome-wide WMH associations found in subjects from CHARGE.
Results-Of 126 spontaneously hypertensive stroke-prone rat genes, 10 were nominally associated with WMH volume or score in subjects from LBC1936, of which 5 (AFP, ALB, GNAI1, RBM8a, and MRPL18) were associated with both WMH volume and score (P<0.05); 2 of the 10 (XPNPEP1, P=6.7x10(-5); FARP1, P=0.024) plus another spontaneously hypertensive stroke-prone rat gene (USMG5, P=0.00014), on chromosomes 10, 13, and 10 respectively, were associated with WMH in subjects from CHARGE. Gene set enrichment showed significant associations for downregulated spontaneously hypertensive stroke-prone rat genes with WMH in humans. In subjects from LBC1936, we replicated CHARGE's genome-wide WMH associations on chromosomes 17 (TRIM65 and TRIM47) and, for the first time, 1 (PMF1).
Conclusions-Despite not passing multiple testing thresholds individually, these genes collectively are relevant to known WMH associations, proposed WMH mechanisms, or dementia: associations with Alzheimer's disease, late-life depression, ATP production, osmotic regulation, neurodevelopmental abnormalities, and cognitive impairment. If replicated further, they suggest a multifactorial nature for WMH and argue for more consideration of vascular contributions to dementia.
C1 [Lopez, Lorna M.; Hernandez, Maria Valdes; Maniega, Susana Munoz; Bastin, Mark E.; Starr, John; Deary, Ian J.; Wardlaw, Joanna M.] Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh EH4 2XU, Midlothian, Scotland.
[Hernandez, Maria Valdes; Maniega, Susana Munoz; Bastin, Mark E.; Wardlaw, Joanna M.] Univ Edinburgh, Brain Res Imaging Ctr, Div Neuroimaging Sci, Edinburgh EH4 2XU, Midlothian, Scotland.
[Smith, Colin] Univ Edinburgh, Ctr Clin Brain Sci, Edinburgh EH4 2XU, Midlothian, Scotland.
[Hill, W. David; Harris, Sarah E.; Porteous, David J.] Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Med Genet Sect, Ctr Genom & Expt Med, Edinburgh EH4 2XU, Midlothian, Scotland.
[Hill, W. David; Harris, Sarah E.; Porteous, David J.] Univ Edinburgh, MRC Inst Genet & Mol Med, Edinburgh EH4 2XU, Midlothian, Scotland.
[Bailey, Emma] Univ London Imperial Coll Sci Technol & Med, Dept Bioengn, London, England.
[McBride, Martin; McClure, John; Graham, Delyth; Dominiczak, Anna] Univ Glasgow, BHF Glasgow Cardiovasc Res Ctr, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland.
[Yang, Qiong] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA.
[Yang, Qiong; Seshadri, Sudha] Framingham Heart Dis Epidemiol Study, Boston, MA USA.
[Fornage, Myriam] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Houston, TX 77030 USA.
[Fornage, Myriam] Univ Texas Hlth Sci Ctr Houston, Inst Mol Med, Houston, TX 77030 USA.
[Ikram, M. Arfan] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.
[Ikram, M. Arfan] Erasmus MC, Dept Radiol, Rotterdam, Netherlands.
[Ikram, M. Arfan] Erasmus MC, Dept Neurol, Rotterdam, Netherlands.
[Ikram, M. Arfan] Netherlands Consortium Hlth Aging, Leiden, Netherlands.
[Debette, Stephanie] Univ Paris 07, INSERM U740 12, Bordeaux, France.
[Debette, Stephanie] Bordeaux Univ, U708, Bordeaux, France.
[Debette, Stephanie] Univ Paris 07, DHU Neurovasc Paris Sorbonne, Dept Neurol, Lariboisiere Hosp, Paris, France.
[Debette, Stephanie] Univ Versailles St Quentin En Yvelines, Versailles, France.
[Debette, Stephanie; Seshadri, Sudha] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02215 USA.
[Launer, Lenore] NIA, Lab Epidemiol & Populat Sci, Intramural Res Program, NIH, Bethesda, MD 20892 USA.
[Bis, Joshua C.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA.
[Schmidt, Reinhold] Med Univ Graz, Dept Neurol, Clin Div Neurogeriatr, Graz, Austria.
RP Wardlaw, JM (reprint author), Univ Edinburgh, Western Gen Hosp, Brain Res Imaging Ctr, Div Neuroimaging Sci, Bramwell Dott Bldg,Crewe Rd, Edinburgh EH4 2XU, Midlothian, Scotland.
EM joanna.wardlaw@ed.ac.uk
OI Seshadri, Sudha/0000-0001-6135-2622; Ikram, Mohammad
Arfan/0000-0003-0372-8585
FU Age UK's Disconnected Mind programme; Research Into Ageing [251, 258];
Biotechnology and Biological Sciences Research Council [BB/F019394/1];
Medical Research Council [G1001401, 8200]; Brain Research Imaging
Centre, The University of Edinburgh Centre for Cognitive Ageing and
Cognitive Epidemiology [G0700704/84698]; Medical Research Council;
British Neuropathological Society; Newby Fund; Scottish Funding Council
Scottish Imaging Network A Platform for Scientific Excellence
Collaboration; European Union Community [HEALTH-F4-2010-241504
EURATRANS]; National Institutes of Ageing (NIA) [N01-AG-12100]; National
Eye Institute; National Institute on Deafness and Other Communication
Disorders; National Heart, Lung, and Blood Institute (NHLBI); NIA
Intramural Research Program; Hjartavernd (the Icelandic Heart
Association); Althingi (the Icelandic Parliament); NHLBI
[HHSN268201100005C, HHSN268201100006C, HHSN268201100007C,
HHSN268201100008C, HHSN268201100009C, HHSN268201100010C,
HHSN268201100011C, HHSN268201100012C, N01-HC-85239]; National Human
Genome Research Institute [U01HG004402]; National Institutes of Health
(NIH) [HHSN268200625226C]; NIH [UL1RR025005]; NIH Roadmap for Medical
Research; Austrian Science Fond [P20545-P05, P13180]; National Institute
of Neurological Disorders and Stroke; NIA [AG-023629, AG-15928,
AG-20098, AG-027058]; National Center for Research Resources
[UL1RR033176]; National Center for Advancing Translational Sciences,
Clinical and Translational Science Institute [UL1TR000124]; National
Institute of Diabetes and Digestive and Kidney Disease [DK063491];
Affymetrix, Inc [N02-HL-6-4278]; Robert Dawson Evans Endowment of the
Department of Medicine at Boston University School of Medicine; Boston
Medical Center; National Institute of Neurological Disorders and Stroke
[R01 NS17950]; National Institute of Aging [R01s AG08122, AG16495,
AG033193]; Netherlands Organization of Scientific Research (NOW)
[175.010.2005.011]; Netherlands Genomics Initiative/NWO [050-060-810];
Erasmus Medical Center; Erasmus University, Rotterdam; NWO, the
Netherlands Organization for the Health Research and Development;
Research Institute for Diseases in the Elderly; Ministry of Education,
Culture and Science; Ministry for Health, Welfare and Sports; European
Commission; Municipality of Rotterdam; Nederlandse Hartstichting
[2009B102]; ZonMW Veni-grant [916.13.054]; NHLBI. [N01-HC-85079,
N01-HC-85086, N01-HC-35129, N01HC-15103, N01 HC-55222, N01-HC-75150,
N01-HC-45133, HHSN268200960009C, HHSN268201200036C, HL080295, HL087652,
HL105756, N01-HC-25195, U01 HL096917, R01 HL093029]; [R01HL087641];
[R01HL59367]; [R01HL086694]; [HL093029]
FX Lothian Birth Cohort 1936 was funded by Age UK's Disconnected Mind
programme (http://www.disconnectedmind.ed.ac.uk) and by Research Into
Ageing (references 251 and 285). Whole-genome association was funded by
Biotechnology and Biological Sciences Research Council (reference
BB/F019394/1), brain image analysis was funded by Medical Research
Council (G1001401 and 8200), and imaging was funded by Brain Research
Imaging Centre (http://www.bric.ed.ac.uk), The University of Edinburgh
Centre for Cognitive Ageing and Cognitive Epidemiology
(http://www.ccace.ed.ac.uk, G0700704/84698). The SHRSP analysis was
funded by Medical Research Council (Dr Bailey), British
Neuropathological Society, Newby Fund, Scottish Funding Council Scottish
Imaging Network A Platform for Scientific Excellence Collaboration
(http://www.sinapse.ac.uk), and European Union Community's
FP7/2007-2013, grant agreement HEALTH-F4-2010-241504 EURATRANS. The
Aging Gene-Environment Susceptibility-Reykjavik Study was funded by
National Institutes of Ageing (NIA), contract N01-AG-12100, National Eye
Institute, National Institute on Deafness and Other Communication
Disorders, National Heart, Lung, and Blood Institute (NHLBI), the NIA
Intramural Research Program, Hjartavernd (the Icelandic Heart
Association), and the Althingi (the Icelandic Parliament). The
Atherosclerosis Risk in Communities Study is a collaborative study
supported by NHLBI contracts (HHSN268201100005C, HHSN268201100006C,
HHSN268201100007C, HHSN268201100008C, HHSN268201100009C,
HHSN268201100010C, and HHSN268201100011C, HHSN268201100012C),
R01HL087641, R01HL59367 and R01HL086694; National Human Genome Research
Institute contract U01HG004402; and National Institutes of Health (NIH)
contract HHSN268200625226C; NIH grant number UL1RR025005, and NIH
Roadmap for Medical Research and grant number HL093029. The Austrian
Stroke Prevention Study was funded by the Austrian Science Fond grant
numbers P20545-P05 and P13180. The Medical University of Graz supports
the databank of the ASPS. The Cardiovascular Health Study was supported
by NHLBI contracts N01-HC-85239, N01-HC-85079 through N01-HC-85086,
N01-HC-35129, N01HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133,
HHSN268200960009C, and HHSN268201200036C and NHLBI grants HL080295,
HL087652, HL105756 with additional contribution from National Institute
of Neurological Disorders and Stroke, AG-023629, AG-15928, AG-20098, and
AG-027058 from the NIA (http://www.chs-nhlbi.org/pi.htm). DNA handling
and genotyping at Cedars-Sinai Medical Center was supported in part by
Cedars-Sinai Board of Governors' Chair in Medical Genetics (JIR), the
National Center for Research Resources, grant UL1RR033176, and is now at
the National Center for Advancing Translational Sciences, Clinical and
Translational Science Institute grant UL1TR000124; in addition to the
National Institute of Diabetes and Digestive and Kidney Disease grant
DK063491 to the Southern California Diabetes Endocrinology Research
Center. The Framingham Heart Study was supported by the NHLBI (Contract
no. N01-HC-25195) and its contract with Affymetrix, Inc for genotyping
services (Contract no.; N02-HL-6-4278); some of this research used the
Linux Cluster for Genetic Analysis (LinGA-II) funded by the Robert
Dawson Evans Endowment of the Department of Medicine at Boston
University School of Medicine and Boston Medical Center; and grants from
the National Institute of Neurological Disorders and Stroke (R01
NS17950), and the National Institute of Aging (R01s AG08122, AG16495,
and AG033193), and the NHLBI (U01 HL096917 and R01 HL093029). The
Rotterdam Study Genome-Wide Association database was funded by the
Netherlands Organization of Scientific Research (NOW; no.
175.010.2005.011); the study was further supported by the Netherlands
Genomics Initiative/NWO project no. 050-060-810; the Erasmus Medical
Center and Erasmus University, Rotterdam; NWO, the Netherlands
Organization for the Health Research and Development, the Research
Institute for Diseases in the Elderly, the Ministry of Education,
Culture and Science, the Ministry for Health, Welfare and Sports, the
European Commission (Dr Graham, XII), and the Municipality of Rotterdam
and Dr Ikram was supported by the Nederlandse Hartstichting grant
2009B102 and ZonMW Veni-grant 916.13.054.
NR 43
TC 6
Z9 6
U1 1
U2 6
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0039-2499
EI 1524-4628
J9 STROKE
JI Stroke
PD FEB
PY 2015
VL 46
IS 2
BP 341
EP 347
DI 10.1161/STROKEAHA.114.007649
PG 7
WC Clinical Neurology; Peripheral Vascular Disease
SC Neurosciences & Neurology; Cardiovascular System & Cardiology
GA AZ8AS
UT WOS:000348437800022
PM 25586835
ER
PT J
AU Qu, W
Waalkes, MP
AF Qu, Wei
Waalkes, Michael P.
TI Metallothionein blocks oxidative DNA damage induced by acute inorganic
arsenic exposure
SO TOXICOLOGY AND APPLIED PHARMACOLOGY
LA English
DT Article
DE Arsenic; Oxidative DNA damage; Metallothionein; Reactive oxygen species
ID GLUTATHIONE CONJUGATE; HUMAN-DISEASE; LIVER-CELLS; NULL MICE; IN-VITRO;
TOXICITY; STRESS; RESISTANCE; CARCINOGENESIS; TRANSCRIPTION
AB We studied how protein metallothionein (MT) impacts arsenic-induced oxidative DNA damage (ODD) using cells that poorly express MT (MT-I/II double knockout embryonic cells; called MT-null cells) and wild-type (WT) MT competent cells. Arsenic (as NaAsO2) was less cytolethal over 24 h in WT cells (LC50 = 11.0 +/- 1.3 mu M; mean +/- SEM) than in MT-null cells (LC50 = 5.6 +/- 1.2 mu M). ODD was measured by the immuno-spin trapping method. Arsenic (1 or 5 mu M; 24 h) induced much less ODD in WT cells (121% and 141% of control, respectively) than in MT-null cells (202% and 260%). In WT cells arsenic caused concentration-dependent increases in MT expression (transcript and protein), and in the metal-responsive transcription factor-1 (MTF-1), which is required to induce the MT gene. In contrast, basal MT levels were not detectable in MT-null cells and unaltered by arsenic exposure. Transfection of MT-I gene into the MT-null cells markedly reduced arsenic-induced ODD levels. The transport genes, Abcc1 and Abcc2 were increased by arsenic in WT cells but either showed no or very limited increases in MT-null cells. Arsenic caused increases in oxidant stress defense genes HO-1 and GST alpha 2 in both WT and MT-null cells, but to much higher levels in WT cells. WT cells appear more adept at activating metal transport systems and oxidant response genes, although the role of MT in these responses is unclear. Overall, MT protects against arsenic-induced ODD in MT competent cells by potential sequestration of scavenging oxidant radicals and/or arsenic. Published by Elsevier Inc.
C1 [Qu, Wei; Waalkes, Michael P.] NIEHS, Div Natl Toxicol Program, Natl Toxicol Program Lab, Res Triangle Pk, NC 27709 USA.
RP Qu, W (reprint author), NIEHS, Box 12233,Mail Drop E1-07,111 Alexander Dr, Res Triangle Pk, NC 27709 USA.
EM qu@niehs.nih.gov
FU NIH, NIEHS, DNTP [ES-102925]
FX The authors thank Drs. William M. Gwinn and Olive Ngalame for critical
review of this manuscript. The authors also thank Matthew W. Bell for
aid with the graphics. All funds for this research were supplied by the
NIH, NIEHS, DNTP (Project # ES-102925).
NR 51
TC 6
Z9 7
U1 0
U2 9
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0041-008X
EI 1096-0333
J9 TOXICOL APPL PHARM
JI Toxicol. Appl. Pharmacol.
PD FEB 1
PY 2015
VL 282
IS 3
BP 267
EP 274
DI 10.1016/j.taap.2014.11.014
PG 8
WC Pharmacology & Pharmacy; Toxicology
SC Pharmacology & Pharmacy; Toxicology
GA CB3EB
UT WOS:000349509900005
PM 25485709
ER
PT J
AU Zhou, LQ
Dean, J
AF Zhou, Li-quan
Dean, Jurrien
TI Reprogramming the genome to totipotency in mouse embryos
SO TRENDS IN CELL BIOLOGY
LA English
DT Review
DE reprogramming; totipotency; epigenetic modification; embryonic genome
activation; preimplantation development
ID HISTONE VARIANT H3.3; ZYGOTIC PATERNAL GENOME; PLURIPOTENT STEM-CELLS;
EARLY MAMMALIAN EMBRYO; PREIMPLANTATION EMBRYOS; DNA-METHYLATION;
GENE-EXPRESSION; SPERM CHROMATIN; TET PROTEINS; IN-VIVO
AB Despite investigative interest, the artificial derivation of pluripotent stem cells remains inefficient and incomplete reprogramming hinders its potential as a reliable tool in regenerative medicine. By contrast, fusion of terminally differentiated gametes at fertilization activates efficient epigenetic reprogramming to ensure totipotency of early embryos. Understanding the epigenetic mechanisms required for the transition from the fertilized egg to the embryo can improve efforts to reprogram differentiated cells to pluripotent/totipotent cells for therapeutic use. We review recent discoveries that are providing insight into the molecular mechanisms required for epigenetic reprogramming to totipotency in vivo.
C1 [Zhou, Li-quan; Dean, Jurrien] NIDDK, Lab Cellular & Dev Biol, NIH, Bethesda, MD 20892 USA.
RP Dean, J (reprint author), NIDDK, Lab Cellular & Dev Biol, NIH, Bethesda, MD 20892 USA.
EM jurriend@helix.nih.gov
FU Intramural Research Program of the National Institutes of Health, NIDDK
[ZIA-DK015603]
FX We thank Dr M.E. Torres-Padilla for her critical reading of the
manuscript and useful suggestions. We apologize to authors whose work
could not be cited because of space constraints. This research was
supported by the Intramural Research Program of the National Institutes
of Health, NIDDK (ZIA-DK015603).
NR 102
TC 9
Z9 10
U1 11
U2 39
PU ELSEVIER SCIENCE LONDON
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0962-8924
J9 TRENDS CELL BIOL
JI Trends Cell Biol.
PD FEB
PY 2015
VL 25
IS 2
BP 82
EP 91
DI 10.1016/j.tcb.2014.09.006
PG 10
WC Cell Biology
SC Cell Biology
GA CB4HT
UT WOS:000349589500005
PM 25448353
ER
PT J
AU Achee, NL
Youngblood, L
Bangs, MJ
Lavery, JV
James, S
AF Achee, Nicole L.
Youngblood, Laura
Bangs, Michael J.
Lavery, James V.
James, Stephanie
TI Considerations for the Use of Human Participants in Vector Biology
Research: A Tool for Investigators and Regulators
SO VECTOR-BORNE AND ZOONOTIC DISEASES
LA English
DT Review
DE Vector; Epidemiology; Risk assessment; Vector control; Entomology
ID HUMAN LANDING CATCHES; REED ARMY INSTITUTE; ANOPHELES-GAMBIAE;
COMPARATIVE SUSCEPTIBILITY; MALARIA TRANSMISSION; DIPTERA-CULICIDAE;
INFECTION; AFRICAN; MODEL; MOSQUITOS
AB A thorough search of the existing literature has revealed that there are currently no published recommendations or guidelines for the interpretation of US regulations on the use of human participants in vector biology research (VBR). An informal survey of vector biologists has indicated that issues related to human participation in vector research have been largely debated by academic, national, and local Institutional Review Boards (IRBs) in the countries where the research is being conducted, and that interpretations and subsequent requirements made by these IRBs have varied widely. This document is intended to provide investigators and corresponding scientific and ethical review committee members an introduction to VBR methods involving human participation and the legal and ethical framework in which such studies are conducted with a focus on US Federal Regulations. It is also intended to provide a common perspective for guiding researchers, IRB members, and other interested parties (i.e., public health officials conducting routine entomological surveillance) in the interpretation of human subjects regulations pertaining to VBR.
C1 [Achee, Nicole L.] Univ Notre Dame, Dept Biol Sci, Eck Inst Global Hlth, Notre Dame, IN 46556 USA.
[Youngblood, Laura] Ctr Dis Control & Prevent, Atlanta, GA USA.
[Bangs, Michael J.] Int SOS, Publ Hlth & Malaria Control, Papua, Indonesia.
[Lavery, James V.] St Michaels Hosp, Li Ka Shing Knowledge Inst, Ctr Eth Social & Cultural Risk, Toronto, ON M5B 1W8, Canada.
[Lavery, James V.] Univ Toronto, Dalla Lana Sch Publ Hlth, Toronto, ON M5S 1A1, Canada.
[Lavery, James V.] Univ Toronto, Joint Ctr Bioeth, Toronto, ON M5S 1A1, Canada.
[James, Stephanie] Fdn Natl Inst Hlth, Bethesda, MD USA.
RP Achee, NL (reprint author), Univ Notre Dame, Dept Biol Sci, Eck Inst Global Hlth, 239 Galvin Life Sci Ctr, Notre Dame, IN 46556 USA.
EM nachee@nd.edu
NR 75
TC 4
Z9 4
U1 1
U2 8
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1530-3667
EI 1557-7759
J9 VECTOR-BORNE ZOONOT
JI Vector-Borne Zoonotic Dis.
PD FEB 1
PY 2015
VL 15
IS 2
BP 89
EP 102
DI 10.1089/vbz.2014.1628
PG 14
WC Public, Environmental & Occupational Health; Infectious Diseases
SC Public, Environmental & Occupational Health; Infectious Diseases
GA CB5QL
UT WOS:000349682500002
PM 25700039
ER
PT J
AU Healy, JM
Reisen, WK
Kramer, VL
Fischer, M
Lindsey, NP
Nasci, RS
Macedo, PA
White, G
Takahashi, R
Khang, L
Barker, CM
AF Healy, Jessica M.
Reisen, William K.
Kramer, Vicki L.
Fischer, Marc
Lindsey, Nicole P.
Nasci, Roger S.
Macedo, Paula A.
White, Gregory
Takahashi, Richard
Khang, La
Barker, Christopher M.
TI Comparison of the Efficiency and Cost of West Nile Virus Surveillance
Methods in California
SO VECTOR-BORNE AND ZOONOTIC DISEASES
LA English
DT Article
DE West Nile virus; California; Surveillance methods; Birds; Cost
effectiveness
ID CULEX-TARSALIS DIPTERA; MOSQUITOS; TRANSMISSION; CULICIDAE; CHICKENS;
EPIDEMIOLOGY; INFECTIONS; PREVENTION; DYNAMICS; PATTERNS
AB Surveillance systems for West Nile virus (WNV) combine several methods to determine the location and timing of viral amplification. The value of each surveillance method must be measured against its efficiency and costs to optimize integrated vector management and suppress WNV transmission to the human population. Here we extend previous comparisons of WNV surveillance methods by equitably comparing the most common methods after standardization on the basis of spatial sampling density and costs, and by estimating optimal levels of sampling effort for mosquito traps and sentinel chicken flocks. In general, testing for evidence of viral RNA in mosquitoes and public-reported dead birds resulted in detection of WNV approximately 2-5 weeks earlier than serological monitoring of sentinel chickens at equal spatial sampling density. For a fixed cost, testing of dead birds reported by the public was found to be the most cost effective of the methods, yielding the highest number of positive results per $1000. Increased spatial density of mosquito trapping was associated with more precise estimates of WNV infection prevalence in mosquitoes. Our findings also suggested that the most common chicken flock size of 10 birds could be reduced to six to seven without substantial reductions in timeliness or sensitivity. We conclude that a surveillance system that uses the testing of dead birds reported by the public complemented by strategically timed mosquito and chicken sampling as agency resources allow would detect viral activity efficiently in terms of effort and costs, so long as susceptible bird species that experience a high mortality rate from infection with WNV, such as corvids, are present in the area.
C1 [Healy, Jessica M.; Reisen, William K.; Barker, Christopher M.] Univ Calif Davis, Ctr Vectorborne Dis, Dept Pathol Microbiol & Immunol, Davis, CA 95616 USA.
[Kramer, Vicki L.] Calif Dept Publ Hlth, Vector Borne Dis Sect, Sacramento, CA USA.
[Fischer, Marc; Lindsey, Nicole P.; Nasci, Roger S.] Ctr Dis Control & Prevent, Div Vector Borne Dis, Ft Collins, CO USA.
[Macedo, Paula A.] Sacramento Yolo Mosquito & Vector Control Dist, Elk Grove, CA USA.
[White, Gregory] Coachella Valley Mosquito & Vector Control Dist, Indio, CA USA.
[Takahashi, Richard; Khang, La] Kern Mosquito & Vector Control Dist, Bakersfield, CA USA.
[Barker, Christopher M.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Barker, CM (reprint author), Univ Calif Davis, Ctr Vector Borne Dis, Davis, CA 95616 USA.
EM cmbarker@ucdavis.edu
FU California Department of Public Health; US Centers for Disease Control
and Prevention; National Institute of Allergy and Infectious Diseases of
the National Institutes of Health [F31AII08189]; Research and Policy for
Infectious Disease Dynamics (RAPIDD) program of the Science & Technology
Directorate, Department of Homeland Security; Fogarty International
Center, National Institutes of Health
FX We thank the Sacramento-Yolo, Kern, and Coachella Valley Mosquito and
Vector Control Districts for their collection of the data used for this
research. In particular, we want to add an additional note of
appreciation to Richard Takahashi, who conducted enhanced surveillance
at Kern MVCD for two years of the study. We also thank Bborie Park for
data management, Kerry Padgett and Leslie Foss for their help with dead
bird data, and the California Department of Public Health and the US
Centers for Disease Control and Prevention for their support and
funding, as well as the National Institute of Allergy and Infectious
Diseases of the National Institutes of Health for their support of J.
Healy under award number F31AII08189. The content is solely the
responsibility of the authors and does not necessarily represent the
official views of the National Institutes of Health. C.M. Barker also
acknowledges support from the Research and Policy for Infectious Disease
Dynamics (RAPIDD) program of the Science & Technology Directorate,
Department of Homeland Security and Fogarty International Center,
National Institutes of Health.
NR 32
TC 4
Z9 4
U1 2
U2 14
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1530-3667
EI 1557-7759
J9 VECTOR-BORNE ZOONOT
JI Vector-Borne Zoonotic Dis.
PD FEB 1
PY 2015
VL 15
IS 2
BP 147
EP 155
DI 10.1089/vbz.2014.1689
PG 9
WC Public, Environmental & Occupational Health; Infectious Diseases
SC Public, Environmental & Occupational Health; Infectious Diseases
GA CB5QL
UT WOS:000349682500009
PM 25700046
ER
PT J
AU Soerensen, M
Nygaard, M
Dato, S
Stevnsner, T
Bohr, VA
Christensen, K
Christiansen, L
AF Soerensen, Mette
Nygaard, Marianne
Dato, Serena
Stevnsner, Tinna
Bohr, Vilhelm A.
Christensen, Kaare
Christiansen, Lene
TI Association study of FOXO3A SNPs and aging phenotypes in Danish
oldest-old individuals
SO AGING CELL
LA English
DT Article
DE aging phenotypes; association study; Forkhead box O3; oldest-old; SNPs
ID TRANSCRIPTION FACTOR FOXO3A; HUMAN LONGEVITY; SIGNALING PATHWAY; MICE;
EPIDEMIOLOGY; HOMEOSTASIS; ACTIVATION; FRACTURES; MORTALITY; AUTOPHAGY
AB FOXO3A variation has repeatedly been reported to associate with human longevity, yet only few studies have investigated whether FOXO3A variation also associates with aging-related traits. Here, we investigate the association of 15 FOXO3A tagging single nucleotide polymorphisms (SNPs) in 1088 oldest-old Danes (age 92-93) with 4 phenotypes known to predict their survival: cognitive function, hand grip strength, activity of daily living (ADL), and self-rated health. Based on previous studies in humans and foxo animal models, we also explore self-reported diabetes, cancer, cardiovascular disease, osteoporosis, and bone (femur/spine/hip/wrist) fracture. Gene-based testing revealed significant associations of FOXO3A variation with ADL (P=0.044) and bone fracture (P=0.006). The single-SNP statistics behind the gene-based analysis indicated increased ADL (decreased disability) and reduced bone fracture risk for carriers of the minor alleles of 8 and 10 SNPs, respectively. These positive directions of effects are in agreement with the positive effects on longevity previously reported for these SNPs. However, when correcting for the test of 9 phenotypes by Bonferroni correction, bone fracture showed borderline significance (P=0.054), while ADL did not (P=0.396). Although the single-SNP associations did not formally replicate in another study population of oldest-old Danes (n=1279, age 94-100), the estimates were of similar direction of effect as observed in the Discovery sample. A pooled analysis of both study populations displayed similar or decreased sized P-values for most associations, hereby supporting the initial findings. Nevertheless, confirmation in additional study populations is needed.
C1 [Soerensen, Mette; Nygaard, Marianne; Dato, Serena; Christensen, Kaare; Christiansen, Lene] Univ Southern Denmark, Inst Publ Hlth, Danish Aging Res Ctr, DK-5000 Odense C, Denmark.
[Soerensen, Mette; Nygaard, Marianne; Christensen, Kaare] Odense Univ Hosp, Dept Clin Genet, DK-5000 Odense C, Denmark.
[Dato, Serena] Univ Calabria, Dept Biol Ecol & Earth Sci, I-87036 Arcavacata Di Rende, Cs, Italy.
[Stevnsner, Tinna; Bohr, Vilhelm A.] Aarhus Univ, Dept Mol Biol & Genet, Danish Aging Res Ctr, DK-8000 Aarhus C, Denmark.
[Bohr, Vilhelm A.] NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA.
[Christensen, Kaare] Odense Univ Hosp, Dept Biochem & Pharmacol, DK-5000 Odense C, Denmark.
RP Soerensen, M (reprint author), Univ Southern Denmark, Inst Publ Hlth, Danish Aging Res Ctr, JB Winsloews Vej 9B, DK-5000 Odense C, Denmark.
EM msoerensen@health.sdu.dk
RI Christensen, Kaare/C-2360-2009; Soerensen, Mette/O-1817-2015;
OI Christensen, Kaare/0000-0002-5429-5292; Soerensen,
Mette/0000-0001-5268-3366; dato, serena/0000-0003-2589-7929
FU Max-Planck Institute for Demographic Research (Rostock, Germany);
European Union [259679]; INTERREG 4 A programme
Syddanmark-Schleswig-K.E.R.N. (by EU funds from the European Regional
Development Fund); National Institute on Aging [P01 AG08761]; Novo
Nordisk Foundation; Aase and Ejnar Danielsen Foundation; Brodrene
Hartmann Foundation; King Christian the 10th Foundation; Einer
Willumsens Mindelegat Foundation; VELUX Foundation; Danish Council for
Independent Research - Medical Sciences
FX The study was financially supported by the Max-Planck Institute for
Demographic Research (Rostock, Germany), the European Union's Seventh
Framework Programme (FP7/2007-2011) under grant agreement no 259679, the
INTERREG 4 A programme Syddanmark-Schleswig-K.E.R.N. (by EU funds from
the European Regional Development Fund), the National Institute on Aging
(P01 AG08761), the Novo Nordisk Foundation, the Aase and Ejnar Danielsen
Foundation, the Brodrene Hartmann Foundation, the King Christian the
10th Foundation, and the Einer Willumsens Mindelegat Foundation. The
Danish Aging Research Center is supported by a grant from the VELUX
Foundation, while Mette Soerensen is supported by an individual
postdoctoral grant from The Danish Council for Independent Research -
Medical Sciences.
NR 45
TC 8
Z9 8
U1 0
U2 8
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 FEB
PY 2015
VL 14
IS 1
BP 60
EP 66
DI 10.1111/acel.12295
PG 7
WC Cell Biology; Geriatrics & Gerontology
SC Cell Biology; Geriatrics & Gerontology
GA CA7KQ
UT WOS:000349096600007
PM 25470651
ER
PT J
AU Mielke, MM
Bandaru, VVR
Han, DF
An, Y
Resnick, SM
Ferrucci, L
Haughey, NJ
AF Mielke, Michelle M.
Bandaru, Veera Venkata Ratnam
Han, Dingfen
An, Yang
Resnick, Susan M.
Ferrucci, Luigi
Haughey, Norman J.
TI Factors affecting longitudinal trajectories of plasma sphingomyelins:
the Baltimore Longitudinal Study of Aging
SO AGING CELL
LA English
DT Article
DE aging; sphingomyelin; dihydrosphingomyelin; human; longitudinal; sex
differences
ID CORONARY-ARTERY-DISEASE; SPHINGOLIPID METABOLISM; CELL-MEMBRANES;
RISK-FACTOR; ATHEROSCLEROSIS; PERTURBATION; FIBROBLASTS; BIOMARKERS;
LONGEVITY; DEMENTIA
AB Sphingomyelin metabolism has been linked to several diseases and to longevity. However, few epidemiological studies have quantified individual plasma sphingomyelin species (identified by acyl-chain length and saturation) or their relationship between demographic factors and disease processes. In this study, we determined plasma concentrations of distinct sphingomyelin species in 992 individuals, aged 55 and older, enrolled in the Baltimore Longitudinal Study of Aging. Participants were followed, with serial measures, up to 6 visits and 38years (3972 total samples). Quantitative analyses were performed on a high-performance liquid chromatography-coupled electrospray ionization tandem mass spectrometer. Linear mixed models were used to assess variation in specific sphingomyelin species and associations with demographics, diseases, medications or lifestyle factors, and plasma cholesterol and triglyceride levels. We found that most sphingomyelin species increased with age. Women had higher plasma levels of all sphingomyelin species and showed steeper trajectories of age-related increases compared to men. African Americans also showed higher circulating sphingomyelin concentrations compared to Caucasians. Diabetes, smoking, and plasma triglycerides were associated with lower levels of many sphingomyelins and dihydrosphingomyelins. Notably, these associations showed specificity to sphingomyelin acyl-chain length and saturation. These results demonstrate that longitudinal changes in circulating sphingomyelin levels are influenced by age, sex, race, lifestyle factors, and diseases. It will be important to further establish the intra-individual age- and sex-specific changes in each sphingomyelin species in relation to disease onset and progression.
C1 [Mielke, Michelle M.] Mayo Clin, Dept Hlth Sci Res & Neurol, Rochester, MN 55905 USA.
[Bandaru, Veera Venkata Ratnam; Haughey, Norman J.] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA.
[Han, Dingfen; Haughey, Norman J.] Johns Hopkins Univ, Sch Med, Dept Psychiat, Baltimore, MD 21205 USA.
[An, Yang; Resnick, Susan M.; Ferrucci, Luigi] NIA, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
RP Mielke, MM (reprint author), Mayo Clin, Dept Hlth Sci Res, Div Epidemiol, 200 First St SW, Rochester, MN 55905 USA.
EM mielke.michelle@mayo.edu
FU National Institutes of Health/National Institute on Aging [U01 AG37526]
FX This work was supported by a grant from the National Institutes of
Health/National Institute on Aging (U01 AG37526) and by the Intramural
Research Program of the National Institutes of Health/National Institute
on Aging.
NR 36
TC 4
Z9 4
U1 2
U2 6
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 FEB
PY 2015
VL 14
IS 1
BP 112
EP 121
DI 10.1111/acel.12275
PG 10
WC Cell Biology; Geriatrics & Gerontology
SC Cell Biology; Geriatrics & Gerontology
GA CA7KQ
UT WOS:000349096600012
PM 25345489
ER
PT J
AU Balachova, TN
Batluk, JV
Bryant, KJ
Shaboltas, AV
AF Balachova, Tatiana N.
Batluk, Julia V.
Bryant, Kendall J.
Shaboltas, Alla V.
TI International Collaboration in HIV Prevention Research: Evidence from a
Research Seminar in Russia Abstracts
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Article
ID INJECTION-DRUG USERS; ST-PETERSBURG; ALCOHOL-CONSUMPTION; OPIOID
DEPENDENCE; SEXUAL PARTNERS; RISK BEHAVIORS; TRANSMISSION; WOMEN;
PREVALENCE; NALTREXONE
AB HIV transmission is a major health concern. Global efforts are necessary to control the spread of infection. International collaborative studies in countries with high rates of new infections are essential for increasing knowledge on the behavioral, social, and biomedical aspects of HIV/AIDS and HIV transmission. Statistics indicate a growing HIV epidemic in Russia. There are alarming proportions of new cases attributed to heterosexual contact, and HIV is increasingly affecting people in the general population who are not part of any traditional high-risk group. Despite recent advances in HIV prevention, data on effective behavioral prevention approaches are limited. There is minimal evidence to suggest which types of prevention will be effective in reducing the risk for HIV transmission among people at risk in the general population. This article presents a review and discussion of an international research seminar, HIV Prevention Research: Evidence-Based Behavioral Approaches. Local and international interdisciplinary researchers gathered for the purposes of exchanging research results and information about ongoing studies, identifying gaps in knowledge, and discussing promising prevention strategies. The overarching goal was to advance HIV prevention research through scientific integration. The seminar provided an excellent platform for building research capacity in interdisciplinary HIV research in Russia and integrating research efforts with the international research community to contribute to HIV prevention research throughout the world.
C1 [Balachova, Tatiana N.] Univ Oklahoma Hlth Sci Ctr, Oklahoma City, OK 73104 USA.
[Batluk, Julia V.; Shaboltas, Alla V.] St Petersburg State Univ, Dept Psychol, St Petersburg 199034, Russia.
[Bryant, Kendall J.] NIAAA, NIH, Rockville, MD 20852 USA.
RP Balachova, TN (reprint author), Univ Oklahoma Hlth Sci Ctr, Dept Pediat, 940NE 13th St,Nicholson Tower,Suite 4900, Oklahoma City, OK 73104 USA.
EM tatiana-balachova@ouhsc.edu
FU National Institute on Alcohol Abuse and Alcoholism [R01AA016234,
3R01AA016234-05S1]; Fogarty International Center (Brain Disorders in the
Developing World: Research Across the Lifespan), NIH; RFBR
FX The seminar was organized by the Preventing FAS/ARND in Russian
Children/Expansion to Interdisciplinary HIV Prevention in Women study
group of the U.S.-Russia Collaborative HIV/AIDS Research Initiative, the
National Institutes of Health (NIH), United States, and the Russian
Foundation for Basic Research (RFBR), Russia. The study was supported by
research grant R01AA016234 and an administrative supplement grant award
3R01AA016234-05S1 from the National Institute on Alcohol Abuse and
Alcoholism and the Fogarty International Center (Brain Disorders in the
Developing World: Research Across the Lifespan), NIH to T. Balachova at
OUHSC and a grant award from RFBR to A. Shaboltas at SPSU. The content
of this publication is solely the responsibility of the authors and does
not necessarily represent the official views of the NIH, NIAAA, and
RFBR.
NR 46
TC 1
Z9 1
U1 4
U2 7
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0889-2229
EI 1931-8405
J9 AIDS RES HUM RETROV
JI Aids Res. Hum. Retrovir.
PD FEB 1
PY 2015
VL 31
IS 2
BP 163
EP 172
DI 10.1089/aid.2014.0078
PG 10
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA CB0KP
UT WOS:000349315100002
PM 25430518
ER
PT J
AU Munger, AM
Chow, DC
Playford, MP
Parikh, NI
Gangcuangco, LMA
Nakamoto, BK
Kallianpur, KJ
Ndhlovu, LC
Shikuma, CM
Mehta, NN
AF Munger, Alana M.
Chow, Dominic C.
Playford, Martin P.
Parikh, Nisha I.
Gangcuangco, Louie Mar A.
Nakamoto, Beau K.
Kallianpur, Kalpana J.
Ndhlovu, Lishomwa C.
Shikuma, Cecilia M.
Mehta, Nehal N.
TI Characterization of Lipid Composition and High-Density Lipoprotein
Function in HIV-Infected Individuals on Stable Antiretroviral Regimens
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Article
ID CHOLESTEROL EFFLUX CAPACITY; NUCLEAR-MAGNETIC-RESONANCE;
CARDIOVASCULAR-DISEASE; MYOCARDIAL-INFARCTION; VITAMIN-D; THERAPY; HDL;
WOMEN; RISK; DYSLIPIDEMIA
AB There is an increase in the cardiovascular disease (CVD) morbidity in individuals infected with HIV that may be due to inflammatory lipid modulation not captured by traditional lipid measures. The objective of this study was to perform advanced lipoprotein phenotyping inclusive of the high-density lipoprotein (HDL) cholesterol efflux capacity and lipoprotein particle concentration and size in a well-phenotyped group of 118 patients infected with HIV. We used simple and multivariable analyses to determine the associations between advanced lipoprotein parameters and known cardiometabolic risk factors. Participants were on stable antiretroviral therapy (ART) and had benign traditional lipid panels [median total cholesterol, low-density lipoprotein (LDL)-C, HDL-C, and triglycerides of 178 mg/dl, 108 mg/dl, 44 mg/dl, and 122.5 mg/dl, respectively]. However, advanced lipoprotein phenotyping demonstrated an elevation of LDL particle number (median of 1,233 nmol/liter) and a decrease in LDL size (median of 20.4 nm), along with a decrease in protective, large HDL particles (median of 3.15 mu mol/liter) and reduced HDL cholesterol efflux capacity in comparison to controls of other studies. HDL cholesterol efflux capacity was associated with HDL levels (beta=0.395, p<0.001), small LDL particle concentration (beta=-0.198, p=0.031), insulin sensitivity by the Matsuda index (beta=0.218, p=0.029), and the Framingham Risk Score (beta=-0.184, p=0.046). We demonstrate an atherogenic lipoprotein profile by NMR spectroscopy and HDL efflux measurement in a group of HIV-infected patients on stable ART with normal lipid panels.
C1 [Munger, Alana M.; Chow, Dominic C.; Parikh, Nisha I.; Gangcuangco, Louie Mar A.; Nakamoto, Beau K.; Kallianpur, Kalpana J.; Ndhlovu, Lishomwa C.; Shikuma, Cecilia M.] Univ Hawaii, Hawaii Ctr AIDS, Honolulu, HI 96822 USA.
[Playford, Martin P.; Mehta, Nehal N.] NHLBI, NIH, Bethesda, MD 20892 USA.
[Nakamoto, Beau K.] Straub Clin & Hosp, Honolulu, HI USA.
[Ndhlovu, Lishomwa C.] Univ Hawaii, John A Burns Sch Med, Dept Trop Med, Honolulu, HI 96822 USA.
RP Mehta, NN (reprint author), NHLBI, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA.
EM nehal.mehta@nih.gov
FU Intramural Grant from the NIH; extramural NIH [R01HL095135, U54RR026136]
FX This study was supported by an Intramural Grant from the NIH (N.N.M.),
extramural NIH Grants R01HL095135 and U54RR026136 (C.M.S.). We thank our
study participants and community physicians for their roles in this
study.
NR 33
TC 5
Z9 5
U1 0
U2 1
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0889-2229
EI 1931-8405
J9 AIDS RES HUM RETROV
JI Aids Res. Hum. Retrovir.
PD FEB 1
PY 2015
VL 31
IS 2
BP 221
EP 228
DI 10.1089/aid.2014.0239
PG 8
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA CB0KP
UT WOS:000349315100011
PM 25416403
ER
PT J
AU Salmeron, BJ
AF Salmeron, Betty Jo
TI The Emotional Nature of Rescue Medicine Assessments
SO AMERICAN JOURNAL OF BIOETHICS
LA English
DT Editorial Material
C1 NIDA IRP, Neuroimaging Res Branch, Baltimore, MD 21224 USA.
RP Salmeron, BJ (reprint author), NIDA IRP, Neuroimaging Res Branch, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM bsalmeron@mail.nih.gov
RI Salmeron, Betty Jo/M-1793-2016
OI Salmeron, Betty Jo/0000-0003-1699-9333
FU Intramural NIH HHS [Z99 DA999999]
NR 10
TC 1
Z9 1
U1 0
U2 2
PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD
PI ABINGDON
PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND
SN 1526-5161
EI 1536-0075
J9 AM J BIOETHICS
JI Am. J. Bioeth.
PD FEB 1
PY 2015
VL 15
IS 2
BP 27
EP 29
DI 10.1080/15265161.2014.990762
PG 3
WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical
SC Social Sciences - Other Topics; Medical Ethics; Social Issues;
Biomedical Social Sciences
GA CB0RC
UT WOS:000349333300006
PM 25674954
ER
EF