FN Thomson Reuters Web of Science™
VR 1.0
PT J
AU Green, KA
Zarek, SM
Catherino, WH
AF Green, Katherine A.
Zarek, Shvetha M.
Catherino, William H.
TI Gynecologic health and disease in relation to the microbiome of the
female reproductive tract
SO FERTILITY AND STERILITY
LA English
DT Review
DE Microbiome; lactobacilli; bacterial vaginosis; sexually transmitted
infection
ID IMMUNODEFICIENCY-VIRUS TYPE-1; PELVIC-INFLAMMATORY-DISEASE;
BACTERIAL-VAGINOSIS; VAGINAL MICROBIOME; GENITAL-TRACT; GRAM STAIN;
NONSPECIFIC VAGINITIS; MENSTRUAL-CYCLE; RISK-FACTORS;
LACTOBACILLUS-ACIDOPHILUS
AB It is well established that the vagina is colonized by bacteria that serve important roles in homeostasis. Imbalances in the proportion of bacteria may lead to a predisposition to infection or reproductive complications. Molecular-based approaches demonstrated a greater degree of microbial diversity both within and between women than previously recognized. The vaginal microbiome may fluctuate during various states of health, such as during the menstrual cycle or after menopause, and there may be differences in the vaginal microbiome between women of different ethnicities. Furthermore, the specific composition of the vaginal microbiome may influence the predisposition to dysbiosis and the transmission of sexually transmitted infections. An understanding of the diversity of the vaginal microbial environment during states of health is essential for the identification of risk factors for disease and the development of appropriate treatment. (C) 2015 by American Society for Reproductive Medicine.
C1 [Green, Katherine A.; Zarek, Shvetha M.; Catherino, William H.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA.
[Catherino, William H.] Uniformed Serv Univ Hlth Sci, Dept Obstet & Gynecol, Bldg A,Room 3078,4301 Jones Bridge Rd, Bethesda, MD 20814 USA.
RP Catherino, WH (reprint author), Uniformed Serv Univ Hlth Sci, Dept Obstet & Gynecol, Bldg A,Room 3078,4301 Jones Bridge Rd, Bethesda, MD 20814 USA.
EM william.catherino@usuhs.edu
FU American Society for Reproductive Medicine; Bayer Schering Pharma;
Abbvie Pharmaceuticals; American Board of Obstetrics and Gynecology;
Kantar Health; Intramural Research Program of the Eunice Kennedy Shriver
National Institute of Child Health and Human Development, National
Institutes of Health, Bethesda, Maryland
FX W.H.C. reports personal fees from American Society for Reproductive
Medicine, grants from Bayer Schering Pharma, personal fees from Abbvie
Pharmaceuticals, personal fees from American Board of Obstetrics and
Gynecology, personal fees from Kantar Health, personal fees from Grand
Rounds Speaker, multiple sites, outside the submitted work; and reports
that his wife is an employee of Recombine (genetic testing, not related
to leiomyomas or gonadal hormones). K.A.G. has nothing to disclose.
S.M.Z. has nothing to disclose.; This study was funded, in part, by the
Intramural Research Program of the Eunice Kennedy Shriver National
Institute of Child Health and Human Development, National Institutes of
Health, Bethesda, Maryland.
NR 89
TC 5
Z9 6
U1 7
U2 15
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0015-0282
EI 1556-5653
J9 FERTIL STERIL
JI Fertil. Steril.
PD DEC
PY 2015
VL 104
IS 6
BP 1351
EP 1357
DI 10.1016/j.fertnstert.2015.10.010
PG 7
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA DC4DC
UT WOS:000369169300004
PM 26597627
ER
PT J
AU Steiner, AZ
Diamond, MP
Legro, RS
Schlaff, WD
Barnhart, KT
Casson, PR
Christman, GM
Alvero, R
Hansen, KR
Geisler, WM
Thomas, T
Santoro, N
Zhang, HP
Eisenberg, E
AF Steiner, Anne Z.
Diamond, Michael P.
Legro, Richard S.
Schlaff, William D.
Barnhart, Kurt T.
Casson, Peter R.
Christman, Gregory M.
Alvero, Ruben
Hansen, Karl R.
Geisler, William M.
Thomas, Tracey
Santoro, Nanette
Zhang, Heping
Eisenberg, Esther
CA Reprod Med Network
TI Chlamydia trachomatis immunoglobulin G3 seropositivity is a predictor of
reproductive outcomes in infertile women with patent fallopian tubes
SO FERTILITY AND STERILITY
LA English
DT Article
DE Chlamydia trachomatis; infertility; pregnancy; ectopic pregnancy
ID SUBFERTILE WOMEN; TUBAL PATHOLOGY; ANTIBODIES; METAANALYSIS; INFECTION;
PREGNANCY; SEROLOGY; HISTORY; RATES; MODEL
AB Objective: To determine if Chlamydia trachomatis (C. trachomatis) seropositivity, as detected by the C. trachomatis elementary body (EB)-based enzyme-linked immunosorbent assay [EB ELISA] predicts pregnancy and pregnancy outcome among infertile women with documented tubal patency.
Design: Cohort study.
Setting: Outpatient clinics.
Patient(s): In all, 1,250 infertile women with documented tubal patency enrolled in 1 of 2 randomized controlled trials: Pregnancy in Polycystic Ovary Syndrome II; and the Assessment of Multiple Intrauterine Gestations From Ovarian Stimulation.
Intervention(s): Sera were analyzed for anti-C. trachomatis immunoglobulin G (IgG) 1 and IgG3 antibodies, using a research C. trachomatis EB ELISA. The optical density (OD)(405) readings of >= 0.35 and >= 0.1 were considered positive for IgG1 and IgG3, respectively.
Main Outcome Measure(s): Primary outcomes included pregnancy, live birth, and ectopic pregnancy. Log-linear regression was used to determine the relative risk after adjusting for age, race, treatment medication, smoking status, and current alcohol use.
Result(s): A total of 243 (19%) women were seropositive for anti-C. trachomatis IgG3. They tended to be nonwhite and smokers. AntiC. trachomatis IgG3 seropositive women were significantly less likely to conceive (risk ratio [RR] 0.65, 95% confidence interval [CI] 0.52-0.83) or to have a live birth (RR 0.59, 95% CI 0.43-0.80); these associations were weakened after adjusting for number of hysterosalpingography-documented patent tubes (RR 0.73, 95% CI 0.56-0.97) and (RR 0.73, 95% CI 0.50-1.04), respectively. AntiC. trachomatis IgG3 seropositive women who conceived had a x2.7 risk (95% CI 1.40-5.34) of ectopic pregnancy.
Conclusion(s): Even in the presence of tubal patency, anti-C. trachomatis IgG3 seropositivity is associated with a lower likelihood of pregnancy. Anti-C. trachomatis IgG3 seropositive women have as high as 3 times the risk of ectopic pregnancy. (C) 2015 by American Society for Reproductive Medicine.
C1 [Steiner, Anne Z.] Univ N Carolina, Dept Obstet & Gynecol, Chapel Hill, NC 27599 USA.
[Diamond, Michael P.] Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI USA.
[Diamond, Michael P.] Georgia Regents Univ, Dept Obstet & Gynecol, Augusta, GA USA.
[Legro, Richard S.] Penn State Univ, Dept Obstet & Gynecol, Hershey, PA USA.
[Schlaff, William D.; Alvero, Ruben; Santoro, Nanette] Univ Colorado, Dept Obstet & Gynecol, Aurora, CO USA.
[Barnhart, Kurt T.] Univ Penn, Dept Obstet & Gynecol, Philadelphia, PA 19104 USA.
[Casson, Peter R.] Univ Vermont, Dept Obstet & Gynecol, Burlington, VT USA.
[Christman, Gregory M.] Univ Michigan, Dept Obstet & Gynecol, Ann Arbor, MI 48109 USA.
[Hansen, Karl R.] Univ Oklahoma, Dept Obstet & Gynecol, Oklahoma City, OK USA.
[Geisler, William M.] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA.
[Thomas, Tracey; Zhang, Heping] Yale Univ, Dept Biostat, New Haven, CT USA.
[Eisenberg, Esther] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
RP Steiner, AZ (reprint author), Univ N Carolina, Sch Med, Dept Obstet & Gynecol, CB 7570,Old Clin Bldg, Chapel Hill, NC 27599 USA.
EM asteiner@med.unc.edu
OI Diamond, Michael/0000-0001-6353-4489
FU Ferring; Astra Zeneca; Euroscreen; Clarus Therapeutics; Takeda; AbbVie
Pharmaceuticals; Bayer Pharmaceuticals; Yale University/Reproductive
Medicine Network/NICHD; Ferring International Pharmascience Center US;
Roche Diagnostics; NICHD; NIH; National Institutes of Health
(NIH)/Eunice Kennedy Shriver National Institute of Child Health and
Human Development (NICHD) [U10HD077844, U10 HD39005, U10 HD38992, U10
HD27049, U10 HD38998, U10 HD055942, HD055944, U10 HD055936, U10HD055925,
U10 U54-HD29834]; NIH [UL1 TR000127]
FX A.Z.S. has nothing to disclose. M.P.D. has nothing to disclose. R.S.L.
reports a grant from Ferring; and personal fees from Ferring, Astra
Zeneca, Euroscreen, Clarus Therapeutics, and Takeda. W.D.S. reports
research support grants from AbbVie Pharmaceuticals. K.T.B. has nothing
to disclose. P.R.C. has nothing to disclose. G.M.C. is on the advisory
board of Bayer Pharmaceuticals; received grants from Bayer
Pharmaceuticals and Abbvie Pharmaceuticals; received honoraria from
Abbvie Pharmaceuticals. R.A. has nothing to disclose. K.R.H.
subcontracted with Yale University/Reproductive Medicine Network/NICHD
for salary support and patient care costs; and has received grants from
Ferring International Pharmascience Center US and Roche Diagnostics.
W.M.G. was contracted by Yale University (a research center of the
Reproductive Medicine Network) to perform the chlamydia serology for the
study; contract funds were research funds that went to University of
Alabama. T.T. reports an Reproductive Medicine Network grant from NICHD.
N.S. has nothing to disclose. H.Z. reports an NIH grant. E.E. has
nothing to disclose.; This work was supported by National Institutes of
Health (NIH)/Eunice Kennedy Shriver National Institute of Child Health
and Human Development (NICHD) grants U10HD077844 (to A.Z.S.), U10
HD39005 (to M.P.D.), U10 HD38992 (to R.S.L.), U10 HD27049 (to K.T.B.),
U10 HD38998 (to R.A. and W.D.S), U10 HD055942, HD055944 (to P.R.C.), U10
HD055936 (to G.M.C.), U10HD055925 (to H.Z.); U10 U54-HD29834 (to the
University of Virginia Center for Research in Reproduction Ligand Assay
and Analysis Core of the Specialized Cooperative Centers Program in
Reproduction and Infertility Research); and an NIH grant UL1 TR000127
(to Pennsylvania State University).
NR 21
TC 2
Z9 2
U1 1
U2 5
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0015-0282
EI 1556-5653
J9 FERTIL STERIL
JI Fertil. Steril.
PD DEC
PY 2015
VL 104
IS 6
BP 1522
EP 1526
DI 10.1016/j.fertnstert.2015.08.022
PG 5
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA DC4DC
UT WOS:000369169300031
PM 26413816
ER
PT J
AU Fagoonee, S
Singh, SR
Altruda, F
Pellicano, R
AF Fagoonee, S.
Singh, S. R.
Altruda, F.
Pellicano, R.
TI Surface markers of gastric cancer stem cells
SO MINERVA BIOTECNOLOGICA
LA English
DT Review
DE Stomach neoplasms; Neoplastic stem cells; Helicobacter; Bone marrow
cells
ID MARROW-DERIVED CELLS; HELICOBACTER-PYLORI INFECTION; LYMPH-NODE
METASTASIS; BONE-MARROW; EPITHELIAL-CELLS; PROGENITOR CELLS; MOUSE
STOMACH; SELF-RENEWAL; IN-VITRO; CD44
AB The integrity of the gastric epithelium is maintained by the gastric stem cells, which proliferate and self-renew, giving rise to transient amplifying cells that replace the constantly renewing epithelium. Since in rapidly renewing organs like the stomach, stem cells live long enough to accumulate the multiple genetic changes required for transformation, it is postulated that resident stem cells may, in a chronically inflamed environment, accumulate a series of genetic and epigenetic changes over time that lead to the emergence of gastric cancer stem cells. Alternatively, the setting of chronic inflammatory stress may lead to loss of the indigenous gastric stem cells from their niches, followed by recruitment and engraftment of bone marrow derived stem cells into the gastric epithelium, thus contributing to gastric cancer. Recently, gastric stem cell responses after Helicobacter pylori (H. pylori) infection and recruitment of bone marrow derived stem cells to the inflammatory site have been reported. Despite the tremendous efforts made to identify markers to isolate gastric cancer stem cells, hitherto, only two molecules have been shown to be promising as marker progenitors: villin and Lgr5. This review highlights the advances in the identification of surface markers of gastric cancer stem cells, with emphasis on the effect of H. pylori infection on the stem cell compartment.
C1 [Fagoonee, S.] Univ Turin, Ctr Mol Biotechnol, Inst Biostruct & Bioimages CNR, Turin, Italy.
[Singh, S. R.] Natl Canc Inst, Basic Res Lab, Frederick, MD USA.
[Altruda, F.] Univ Turin, Mol Biotechnol Ctr, Turin, Italy.
[Pellicano, R.] Molinette Mauriziano Hosp, Dept Gastroenterol & Hepatol, Turin, Italy.
RP Pellicano, R (reprint author), Molinette Hosp SGAS, Dept Gastroenterol & Hepatol, Via Cavour 31, I-10126 Turin, Italy.
EM rinaldo_pellican@hotmail.com
RI Singh, Shree Ram/B-7614-2008
OI Singh, Shree Ram/0000-0001-6545-583X
NR 75
TC 0
Z9 0
U1 3
U2 8
PU EDIZIONI MINERVA MEDICA
PI TURIN
PA CORSO BRAMANTE 83-85 INT JOURNALS DEPT., 10126 TURIN, ITALY
SN 1120-4826
EI 1827-160X
J9 MINERVA BIOTECNOL
JI Minerva Biotechnol.
PD DEC
PY 2015
VL 27
IS 4
BP 225
EP 233
PG 9
WC Biotechnology & Applied Microbiology
SC Biotechnology & Applied Microbiology
GA DC4SO
UT WOS:000369210800010
ER
PT J
AU Captur, G
Zemrak, F
Muthurangu, V
Petersen, SE
Li, CM
Bassett, P
Kawel-Boehm, N
McKenna, WJ
Elliott, PM
Lima, JAC
Bluemke, DA
Moon, JC
AF Captur, Gabriella
Zemrak, Filip
Muthurangu, Vivek
Petersen, Steffen E.
Li, Chunming
Bassett, Paul
Kawel-Boehm, Nadine
McKenna, William J.
Elliott, Perry M.
Lima, Joao A. C.
Bluemke, David A.
Moon, James C.
TI Fractal Analysis of Myocardial Trabeculations in 2547 Study
Participants: Multi-Ethnic Study of Atherosclerosis
SO RADIOLOGY
LA English
DT Article
ID LEFT-VENTRICULAR NONCOMPACTION; MAGNETIC-RESONANCE; NON-COMPACTION;
CARDIOMYOPATHY; DIAGNOSIS; MRI
AB Purpose: To quantitatively determine the population variation and relationship of left ventricular (LV) trabeculation to LV function, structure, and clinical variables.
Materials and Methods: This HIPAA-compliant multicenter study was approved by institutional review boards of participating centers. All participants provided written informed consent. Participants from the Multi-Ethnic Study of Atherosclerosis with cardiac magnetic resonance (MR) data were evaluated to quantify LV trabeculation as a fractal dimension (FD). Entire cohort participants free of cardiac disease, hypertrophy, hypertension, and diabetes were stratified by body mass index (BMI) into three reference groups (BMI <25 kg/m(2); BMI >= 25 kg/m(2) to <30 kg/m(2); and BMI >= 30 kg/m(2)) to explore maximal apical FD (FDMaxApical). Multivariable linear regression models determined the relationship between FD and other parameters.
Results: Included were 2547 participants (mean age, 68.7 years +/- 9.1 [standard deviation]; 1211 men). FDMaxApical are in arbitrary units. FDMaxApical reference ranges for BMI 30 kg/m(2) or greater (n = 163), 25 kg/m(2) or greater to less than 30 kg/m(2) (n = 206), and less than 25 kg/m(2) (n = 235) were 1.203 +/- 0.06 (95% confidence interval: 1.194, 1.212), 1.194 +/- 0.06 (95% confidence interval: 1.186, 1.202), and 1.169 +/- 0.05 (95% confidence interval: 1.162, 1.176), respectively. In the entire cohort, adjusted for anthropometrics, trabeculation was higher in African American participants (standardized beta [s beta] = 0.09; P <= .001) and Hispanic participants (s beta = 0.05; P = .013) compared with white participants and was also higher in African American participants compared with Chinese American participants (s beta = 0.08; P = .01), and this persisted after adjustment for hypertension and LV size. Hypertension (s beta = 0.07; P < .001), LV mass (s beta = 0.22; P < .001), and wall thickness (s beta = 0.27; P < .001) were positively associated with FDMaxApical even after adjustment. In the group with BMIs less than 25 kg/m(2), Chinese American participants had less trabeculation than white participants (s beta = 20.15; P = .032).
Conclusion: Fractal analysis of cardiac MR imaging data measures endocardial complexity, which helps to differentiate normal from abnormal trabecular patterns in healthy versus diseased hearts. Trabeculation is influenced by race and/or ethnicity and, more importantly, by cardiac loading conditions and comorbidities. Clinicians who interpret cine MR imaging data should expect slightly less endocardial complexity in Chinese American patients and more in African American patients, Hispanic patients, hypertensive patients, and those with hypertrophy. (C) RSNA, 2015
C1 [Captur, Gabriella; Bassett, Paul; McKenna, William J.; Elliott, Perry M.; Moon, James C.] Heart Hosp, Div Cardiovasc Imaging & Biostat, 16-18 Westmoreland St, London W1G 8PH, England.
[Captur, Gabriella; Muthurangu, Vivek; McKenna, William J.; Elliott, Perry M.; Moon, James C.] UCL, UCL Inst Cardiovasc Sci, London, England.
[Zemrak, Filip; Petersen, Steffen E.] Queen Mary Univ London, Barts & London Sch Med & Dent, Cardiovasc Biomed Res Unit, London, England.
[Zemrak, Filip; Petersen, Steffen E.] London Chest Hosp, Div Cardiovasc Imaging, London E2 9JX, England.
[Muthurangu, Vivek] UCL, Ctr Cardiovasc Imaging, London, England.
[Muthurangu, Vivek] Great Ormond St Hosp Sick Children, London, England.
[Li, Chunming] Univ Penn, Dept Radiol, Philadelphia, PA 19104 USA.
[Kawel-Boehm, Nadine] Hosp Graubuenden, Dept Radiol, Loestrasse, Switzerland.
[Lima, Joao A. C.; Bluemke, David A.] NIH, Dept Radiol & Imaging Sci, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA.
[Bluemke, David A.] Johns Hopkins Univ Hosp, Dept Cardiovasc Imaging, Baltimore, MD 21287 USA.
RP Moon, JC (reprint author), Heart Hosp, Div Cardiovasc Imaging & Biostat, 16-18 Westmoreland St, London W1G 8PH, England.; Moon, JC (reprint author), UCL, UCL Inst Cardiovasc Sci, London, England.
EM j.moon@ucl.ac.uk
RI Petersen, Steffen/A-8389-2011;
OI Petersen, Steffen/0000-0003-4622-5160; moon, james/0000-0001-8071-1491
FU National Institutes of Health [N01 HC 95159, N01 HC 95160, N01 HC 95161,
N01 HC 95162, N01 HC 95163, N01 HC 95164, N01 HC 95165, N01 HC 95166,
N01 HC 95168, CL090019, EB000072]
FX This research was supported by the National Institutes of Health (grants
N01 HC 95159, N01 HC 95160, N01 HC 95161, N01 HC 95162, N01 HC 95163,
N01 HC 95164, N01 HC 95165, N01 HC 95166, N01 HC 95168, CL090019, and
EB000072).
NR 22
TC 6
Z9 6
U1 1
U2 3
PU RADIOLOGICAL SOC NORTH AMERICA
PI OAK BROOK
PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA
SN 0033-8419
J9 RADIOLOGY
JI Radiology
PD DEC
PY 2015
VL 277
IS 3
BP 707
EP 715
DI 10.1148/radiol.2015142948
PG 9
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA DC9EY
UT WOS:000369525100010
PM 26069924
ER
PT J
AU Muller, BG
Shih, JH
Sankineni, S
Marko, J
Rais-Bahrami, S
George, AK
de la Rosette, JJMCH
Merino, MJ
Wood, BJ
Pinto, P
Choyke, PL
Turkbey, B
AF Muller, Berrend G.
Shih, Joanna H.
Sankineni, Sandeep
Marko, Jamie
Rais-Bahrami, Soroush
George, Arvin Koruthu
de la Rosette, Jean J. M. C. H.
Merino, Maria J.
Wood, Bradford J.
Pinto, Peter
Choyke, Peter L.
Turkbey, Baris
TI Prostate Cancer: Interobserver Agreement and Accuracy with the Revised
Prostate Imaging Reporting and Data System at Multiparametric MR Imaging
SO RADIOLOGY
LA English
DT Article
ID TRANSRECTAL ULTRASOUND BIOPSY; RADS SCORING SYSTEM; IN-BORE BIOPSY;
FUSION; VALIDATION; DIAGNOSIS
AB Purpose: To evaluate accuracy and interobserver variability with the use of the Prostate Imaging Reporting and Data System (PI-RADS) version 2.0 for detection of prostate cancer at multiparametric magnetic resonance (MR) imaging in a biopsy-naive patient population.
Materials and Methods: This retrospective HIPAA-compliant study was approved by the local ethics committee, and written informed consent was obtained from all patients for use of their imaging and histopathologic data in future research studies. In 101 biopsy-naive patients with elevated prostate-specific antigen levels who underwent multiparametric MR imaging of the prostate and subsequent transrectal ultrasonography (US)-MR imaging fusion-guided biopsy, suspicious lesions detected at multiparametric MR imaging were scored by five readers who were blinded to pathologic results by using to the newly revised PI-RADS and the scoring system developed in-house. Interobserver agreement was evaluated by using k statistics, and the correlation of pathologic results with each of the two scoring systems was evaluated by using the Kendall T correlation coefficient.
Results: Specimens of 162 lesions in 94 patients were sampled by means of transrectal US-MR imaging fusion biopsy. Results for 87 (54%) lesions were positive for prostate cancer. Kendall T values with the PI-RADS and the in-house-developed scoring system, respectively, at T2-weighted MR imaging in the peripheral zone were 0.51 and 0.17 and in the transitional zone, 0.45 and 20.11; at diffusion-weighted MR imaging, 0.42 and 0.28; at dynamic contrast material-enhanced MR imaging, 0.23 and 0.24, and overall suspicion scores were 0.42 and 0.49. Median k scores among all possible pairs of readers for PI-RADS and the in-house-developed scoring system, respectively, for T2-weighted MR images in the peripheral zone were 0.47 and 0.15; transitional zone, 0.37 and 0.07; diffusion-weighted MR imaging, 0.41 and 0.57; dynamic contrast-enhanced MR imaging, 0.48 and 0.41; and overall suspicion scores, 0.46 and 0.55.
Conclusion: Use of the revised PI-RADS provides moderately reproducible MR imaging scores for detection of clinically relevant disease. (C) RSNA, 2015
C1 [Muller, Berrend G.; Sankineni, Sandeep; Choyke, Peter L.; Turkbey, Baris] NCI, Mol Imaging Program, NIH, 10 Ctr Dr,MSC 1182,Bldg 10,Room B3B85, Bethesda, MD 20892 USA.
[Shih, Joanna H.] NCI, Biometr Res Branch, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA.
[Rais-Bahrami, Soroush; George, Arvin Koruthu; Pinto, Peter] NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Merino, Maria J.] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA.
[Wood, Bradford J.] NCI, Ctr Intervent Oncol, NIH, Bethesda, MD 20892 USA.
[Muller, Berrend G.; de la Rosette, Jean J. M. C. H.] AMC Univ Hosp, Dept Urol, Amsterdam, Netherlands.
[Marko, Jamie] Uniformed Serv Univ Hlth Sci, Dept Radiol & Radiol Sci, Edward Hebert Sch Med, Bethesda, MD 20814 USA.
RP Turkbey, B (reprint author), NCI, Mol Imaging Program, NIH, 10 Ctr Dr,MSC 1182,Bldg 10,Room B3B85, Bethesda, MD 20892 USA.
EM turkbeyi@mail.nih.gov
NR 29
TC 35
Z9 38
U1 2
U2 5
PU RADIOLOGICAL SOC NORTH AMERICA
PI OAK BROOK
PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA
SN 0033-8419
J9 RADIOLOGY
JI Radiology
PD DEC
PY 2015
VL 277
IS 3
BP 741
EP 750
DI 10.1148/radiol.2015142818
PG 10
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA DC9EY
UT WOS:000369525100014
PM 26098458
ER
PT J
AU Sullivan, DC
Obuchowski, NA
Kessler, LG
Raunig, DL
Gatsonis, C
Huang, EP
Kondratovich, M
McShane, LM
Reeves, AP
Barboriak, DP
Guimaraes, AR
Wahl, RL
AF Sullivan, Daniel C.
Obuchowski, Nancy A.
Kessler, Larry G.
Raunig, David L.
Gatsonis, Constantine
Huang, Erich P.
Kondratovich, Marina
McShane, Lisa M.
Reeves, Anthony P.
Barboriak, Daniel P.
Guimaraes, Alexander R.
Wahl, Richard L.
CA RSNA-QIBA Metrol Working Grp
TI Metrology Standards for Quantitative Imaging Biomarkers
SO RADIOLOGY
LA English
DT Article
ID STATISTICAL-METHODS; TECHNICAL PERFORMANCE; GOLD STANDARD; LUNG-CANCER;
REPRODUCIBILITY; AGREEMENT; PET; ISSUES
AB Although investigators in the imaging community have been active in developing and evaluating quantitative imaging biomarkers (QIBs), the development and implementation of QIBs have been hampered by the inconsistent or incorrect use of terminology or methods for technical performance and statistical concepts. Technical performance is an assessment of how a test performs in reference objects or subjects under controlled conditions. In this article, some of the relevant statistical concepts are reviewed, methods that can be used for evaluating and comparing QIBs are described, and some of the technical performance issues related to imaging biomarkers are discussed. More consistent and correct use of terminology and study design principles will improve clinical research, advance regulatory science, and foster better care for patients who undergo imaging studies. (C)RSNA, 2015
C1 [Sullivan, Daniel C.; Barboriak, Daniel P.] Duke Univ, Med Ctr, Dept Radiol, Box 2715, Durham, NC 27710 USA.
[Obuchowski, Nancy A.] Cleveland Clin Fdn, Dept Quantitat Hlth Sci, Cleveland, OH 44195 USA.
[Kessler, Larry G.] Univ Washington, Dept Publ Hlth, Seattle, WA 98195 USA.
[Raunig, David L.] ICON Med, Dept Informat, Washington, PA USA.
[Gatsonis, Constantine] Brown Univ, Ctr Stat Sci, Providence, RI 02912 USA.
[Huang, Erich P.; McShane, Lisa M.] NCI, Bethesda, MD 20892 USA.
[Kondratovich, Marina] US FDA, Ctr Devices & Radiol Hlth, White Oak, MD USA.
[Reeves, Anthony P.] Cornell Univ, Dept Elect & Comp Engn, Ithaca, NY USA.
[Guimaraes, Alexander R.] Oregon Hlth & Sci Univ, Dept Radiol, Portland, OR 97201 USA.
[Wahl, Richard L.] Washington Univ, Sch Med, Mallinckrodt Inst Radiol, St Louis, MO USA.
RP Sullivan, DC (reprint author), Duke Univ, Med Ctr, Dept Radiol, Box 2715, Durham, NC 27710 USA.
EM daniel.sullivan@duke.edu
FU National Institutes of Health [HHSN268201000050C]
FX This research was supported by the National Institutes of Health (grant
no. HHSN268201000050C).
NR 31
TC 19
Z9 19
U1 3
U2 8
PU RADIOLOGICAL SOC NORTH AMERICA
PI OAK BROOK
PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA
SN 0033-8419
J9 RADIOLOGY
JI Radiology
PD DEC
PY 2015
VL 277
IS 3
BP 813
EP 825
DI 10.1148/radiol.2015142202
PG 13
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA DC9EY
UT WOS:000369525100021
PM 26267831
ER
PT J
AU Lee, KS
Burke, TR
Park, JE
Bang, JK
Lee, E
AF Lee, Kyung S.
Burke, Terrence R., Jr.
Park, Jung-Eun
Bang, Jeong K.
Lee, Eunhye
TI Recent Advances and New Strategies in Targeting Plk1 for Anticancer
Therapy
SO TRENDS IN PHARMACOLOGICAL SCIENCES
LA English
DT Review
ID POLO-LIKE-KINASE; ACUTE MYELOID-LEUKEMIA; HUMAN CANCER-CELLS;
PROTEIN-PROTEIN INTERACTIONS; ACUTE MYELOGENOUS LEUKEMIA; SMALL-MOLECULE
INHIBITORS; BOX DOMAIN; ANTITUMOR-ACTIVITY; FLUORESCENCE POLARIZATION;
HEMATOLOGIC MALIGNANCIES
AB Polo-like kinase 1 (Plk1) plays key roles in regulating mitotic processes that are crucial for cellular proliferation. Overexpression of Plk1 is tightly associated with the development of particular cancers in humans, and a large body of evidence suggests that Plk1 is an attractive target for anticancer therapeutic development. Drugs targeting Plk1 can potentially be directed at two distinct sites: the N-terminal catalytic kinase domain (KD), which phosphorylates substrates, and the C-terminal polo-box domain (PBD) which is essential for protein-protein interactions. In this review we summarize recent advances and new challenges in the development of Plk1 inhibitors targeting these two domains. We also discuss novel strategies for designing and developing next-generation inhibitors to effectively treat Plk1-associated human disorders.
C1 [Lee, Kyung S.; Park, Jung-Eun; Lee, Eunhye] NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Burke, Terrence R., Jr.] Natl Canc Inst Frederick, Chem Biol Lab, Ctr Canc Res, Frederick, MD 21702 USA.
[Bang, Jeong K.] Korea Basic Sci Inst, Div Magnet Resonance, Chungbuk 363883, Cheongwon, South Korea.
RP Lee, KS (reprint author), NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM kyunglee@gmail.nih.gov
FU National Institutes of Health (NIH) National Cancer Institute (NCI);
Korea Basic Science Institute [T35418]; Korean Biomedical Scientist
Fellowship from the KRIBB Research Initiative Program, Korea Research
Institute of Bioscience and Biotechnology, Republic of Korea
FX We would like to thank Klaus Strebhardt for critical reading of the
manuscript and many colleagues for generously sharing their views and
insights. We apologize to all authors whose work could not be cited
owing to space limitations. This research was supported in part by the
Intramural Research Program of the National Institutes of Health (NIH)
National Cancer Institute (NCI) (K.S.L. and T.R.B), Korea Basic Science
Institute grant T35418 (J.K.B.), and a Korean Biomedical Scientist
Fellowship from the KRIBB Research Initiative Program, Korea Research
Institute of Bioscience and Biotechnology, Republic of Korea.
NR 153
TC 10
Z9 10
U1 7
U2 22
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 DEC
PY 2015
VL 36
IS 12
BP 858
EP 877
DI 10.1016/j.tips.2015.08.013
PG 20
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA DC6RV
UT WOS:000369348200005
PM 26478211
ER
PT J
AU Chandler, RK
Kahana, SY
Fletcher, B
Jones, D
Finger, MS
Aklin, WM
Hamill, K
Webb, C
AF Chandler, Redonna K.
Kahana, Shoshana Y.
Fletcher, Bennett
Jones, Dionne
Finger, Matthew S.
Aklin, Will M.
Hamill, Kathleen
Webb, Candace
TI Data Collection and Harmonization in HIV Research: The Seek, Test,
Treat, and Retain Initiative at the National Institute on Drug Abuse
SO AMERICAN JOURNAL OF PUBLIC HEALTH
LA English
DT Editorial Material
ID CHRONIC MENTAL-ILLNESS; ANTIRETROVIRAL THERAPY; PREVENTION; ADHERENCE;
PEOPLE; CARE; COVERAGE; DISORDERS; INFECTION; HIV/AIDS
AB Large-scale, multisite data sets offer the potential for exploring the public health benefits of biomedical interventions. Data harmonization is an emerging strategy to increase the comparability of research data collected across independent studies, enabling research questions to be addressed beyond the capacity of any individual study.
The National Institute on Drug Abuse recently implemented this novel strategy to prospectively collect and harmonize data across 22 independent research studies developing and empirically testing interventions to effectively deliver an HIV continuum of care to diverse drug-abusing populations.
We describe this data collection and harmonization effort, collectively known as the Seek, Test, Treat, and Retain Data Collection and Harmonization Initiative, which can serve as a model applicable to other research endeavors.
C1 [Chandler, Redonna K.; Kahana, Shoshana Y.; Fletcher, Bennett; Jones, Dionne; Finger, Matthew S.; Aklin, Will M.; Hamill, Kathleen] NIDA, NIH, Bethesda, MD 20892 USA.
[Webb, Candace] HIV AIDS Bur, Hlth Resources & Serv Adm, Rockville, MD USA.
RP Chandler, RK (reprint author), NIH, 6701 Democracy Blvd,Off 934, Bethesda, MD 20892 USA.
EM redonna.chandler@nih.gov
NR 28
TC 5
Z9 5
U1 0
U2 2
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 DEC
PY 2015
VL 105
IS 12
BP 2416
EP 2422
DI 10.2105/AJPH.2015.302788
PG 7
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA DC4BB
UT WOS:000369163600020
PM 26469642
ER
PT J
AU Dawber, TR
Moore, FE
Mann, GV
AF Dawber, Thomas R.
Moore, Felix E.
Mann, George V.
TI II. Coronary Heart Disease in the Framingham Study (Reprinted from AM J
Public Health, vol 47, pg 4-24, 1957)
SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY
LA English
DT Reprint
C1 [Dawber, Thomas R.; Moore, Felix E.; Mann, George V.] NIH, Natl Heart Inst, Publ Hlth Serv, Bldg 10, Bethesda, MD 20892 USA.
RP Dawber, TR (reprint author), NIH, Natl Heart Inst, Publ Hlth Serv, Bldg 10, Bethesda, MD 20892 USA.
NR 17
TC 1
Z9 1
U1 3
U2 7
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 DEC
PY 2015
VL 44
IS 6
BP 1767
EP 1780
DI 10.1093/ije/dyv346
PG 14
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA DC0NW
UT WOS:000368915400003
PM 26705414
ER
PT J
AU Hung, GCL
Hahn, J
Alamiri, B
Buka, SL
Goldstein, JM
Laird, N
Nelson, CA
Smoller, W
Gilman, SE
AF Hung, Galen Chin-Lun
Hahn, Jill
Alamiri, Bibi
Buka, Stephen L.
Goldstein, Jill M.
Laird, Nan
Nelson, Charles A.
Smoller, Jordan W.
Gilman, Stephen E.
TI Socioeconomic disadvantage and neural development from infancy through
early childhood
SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE Neural development; soft signs; neurological abnormality; socioeconomic
status
ID NEUROLOGICAL SOFT SIGNS; COLLABORATIVE PERINATAL PROJECT; 1ST-EPISODE
SCHIZOPHRENIA; BIPOLAR DISORDER; SEX-DIFFERENCES; BIRTH COHORT;
CHILDREN; STRESS; NEURODEVELOPMENT; OUTCOMES
AB Background: Early social experiences are believed to shape neurodevelopment, with potentially lifelong consequences. Yet minimal evidence exists regarding the role of the social environment on children's neural functioning, a core domain of neurodevelopment.
Methods: We analysed data from 36 443 participants in the United States Collaborative Perinatal Project, a socioeconomically diverse pregnancy cohort conducted between 1959 and 1974. Study outcomes included: physician (neurologist or paediatrician)-rated neurological abnormality neonatally and thereafter at 4 months and 1 and 7 years; indicators of neurological hard signs and soft signs; and indicators of autonomic nervous system function.
Results: Children born to socioeconomically disadvantaged parents were more likely to exhibit neurological abnormalities at 4 months [odds ratio (OR) = 1.20; 95% confidence interval (CI) = 1.06, 1.37], 1 year (OR = 1.35; CI = 1.17, 1.56), and 7 years (OR = 1.67; CI = 1.48, 1.89), and more likely to exhibit neurological hard signs (OR = 1.39; CI = 1.10, 1.76), soft signs (OR = 1.26; CI = 1.09, 1.45) and autonomic nervous system dysfunctions at 7 years. Pregnancy and delivery complications, themselves associated with socioeconomic disadvantage, did not account for the higher risks of neurological abnormalities among disadvantaged children.
Conclusions: Parental socioeconomic disadvantage was, independently from pregnancy and delivery complications, associated with abnormal child neural development during the first 7 years of life. These findings reinforce the importance of the early environment for neurodevelopment generally, and expand knowledge regarding the domains of neurodevelopment affected by environmental conditions. Further work is needed to determine the mechanisms linking socioeconomic disadvantage with children's neural functioning, the timing of such mechanisms and their potential reversibility.
C1 [Hung, Galen Chin-Lun] Taipei City Hosp, Taipei City Psychiat Ctr, Dept Gen Psychiat, Taipei, Taiwan.
[Hung, Galen Chin-Lun] Natl Yang Ming Univ, Sch Med, Dept Publ Hlth, Taipei 112, Taiwan.
[Hahn, Jill; Gilman, Stephen E.] Harvard Univ, Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA USA.
[Alamiri, Bibi] Lahey Hosp & Med Ctr, Sect Child & Adolescent Psychiat, Burlington, MA USA.
[Alamiri, Bibi; Gilman, Stephen E.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Buka, Stephen L.] Brown Univ, Sch Publ Hlth, Dept Epidemiol, Providence, RI 02912 USA.
[Goldstein, Jill M.] Brigham & Womens Hosp, Dept Psychiat, Boston, MA USA.
[Goldstein, Jill M.] Brigham & Womens Hosp, Dept Med, Boston, MA USA.
[Laird, Nan] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Nelson, Charles A.] Harvard Univ, Sch Med, Boston Childrens Hosp, Dept Pediat, Boston, MA USA.
[Smoller, Jordan W.] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Boston, MA 02114 USA.
[Smoller, Jordan W.; Gilman, Stephen E.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
[Smoller, Jordan W.] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Gilman, Stephen E.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, Rockville, MD USA.
RP Gilman, SE (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, 6100 Execut Blvd,Room 7B13M, Rockville, MD 20852 USA.
EM stephen.gilman@nih.gov
OI Gilman, Stephen/0000-0002-8331-6419
FU National Institutes of Health [RO1MH087544, P50MH082679]; Intramural
Research Program of the Eunice Kennedy Shriver National Institute of
Child Health and Human Development
FX This work was supported in part by grants from the National Institutes
of Health [RO1MH087544 to S.E.G. and P50MH082679 to J.M.G.] and the
Intramural Research Program of the Eunice Kennedy Shriver National
Institute of Child Health and Human Development.
NR 79
TC 5
Z9 5
U1 1
U2 9
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 DEC
PY 2015
VL 44
IS 6
BP 1889
EP 1899
DI 10.1093/ije/dyv303
PG 11
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA DC0NW
UT WOS:000368915400019
ER
PT J
AU Stirratt, MJ
Dunbar-Jacob, J
Crane, HM
Simoni, JM
Czajkowski, S
Hilliard, ME
Aikens, JE
Hunter, CM
Velligan, DI
Huntley, K
Ogedegbe, G
Rand, CS
Schron, E
Nilsen, WJ
AF Stirratt, Michael J.
Dunbar-Jacob, Jacqueline
Crane, Heidi M.
Simoni, Jane M.
Czajkowski, Susan
Hilliard, Marisa E.
Aikens, James E.
Hunter, Christine M.
Velligan, Dawn I.
Huntley, Kristen
Ogedegbe, Gbenga
Rand, Cynthia S.
Schron, Eleanor
Nilsen, Wendy J.
TI Self-report measures of medication adherence behavior: recommendations
on optimal use
SO TRANSLATIONAL BEHAVIORAL MEDICINE
LA English
DT Article
DE Adherence; Compliance; Self-management; Medication; Self-report
ID FACE-TO-FACE; COMBINATION ANTIRETROVIRAL THERAPY; VIROLOGICAL TREATMENT
RESPONSE; DIABETES TREATMENT ADHERENCE; RANDOMIZED CONTROLLED-TRIAL;
SEVERE MENTAL-ILLNESS; INJECTING DRUG-USERS; VISUAL ANALOG SCALE;
QUALITY-OF-LIFE; PSYCHOMETRIC PROPERTIES
AB Medication adherence plays an important role in optimizing the outcomes of many treatment and preventive regimens in chronic illness. Self-report is the most common method for assessing adherence behavior in research and clinical care, but there are questions about its validity and precision. The NIH Adherence Network assembled a panel of adherence research experts working across various chronic illnesses to review self-report medication adherence measures and research on their validity. Self-report medication adherence measures vary substantially in their question phrasing, recall periods, and response items. Self-reports tend to overestimate adherence behavior compared with other assessment methods and generally have high specificity but low sensitivity. Most evidence indicates that self-report adherence measures show moderate correspondence to other adherence measures and can significantly predict clinical outcomes. The quality of self-report adherence measures may be enhanced through efforts to use validated scales, assess the proper construct, improve estimation, facilitate recall, reduce social desirability bias, and employ technologic delivery. Self-report medication adherence measures can provide actionable information despite their limitations. They are preferred when speed, efficiency, and low-cost measures are required, as is often the case in clinical care.
C1 [Stirratt, Michael J.] NIMH, Div AIDS Res, NIH, Bethesda, MD 20892 USA.
[Dunbar-Jacob, Jacqueline] Univ Pittsburgh, Sch Nursing, Pittsburgh, PA 15261 USA.
[Crane, Heidi M.] Univ Washington, Div Infect Dis, Seattle, WA 98195 USA.
[Simoni, Jane M.] Univ Washington, Dept Psychol, Seattle, WA 98195 USA.
[Czajkowski, Susan] NHLBI, NIH, Bethesda, MD 20892 USA.
[Hilliard, Marisa E.] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA.
[Aikens, James E.] Univ Michigan, Dept Family Med, Ann Arbor, MI 48109 USA.
[Hunter, Christine M.] NIDDK, NIH, Bethesda, MD 20892 USA.
[Velligan, Dawn I.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA.
[Huntley, Kristen] NIDA, NIH, Bethesda, MD 20892 USA.
[Ogedegbe, Gbenga] NYU, Sch Med, New York, NY USA.
[Rand, Cynthia S.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
[Schron, Eleanor] NEI, NIH, Bethesda, MD 20892 USA.
[Nilsen, Wendy J.] Natl Sci Fdn, Arlington, VA 22230 USA.
RP Stirratt, MJ (reprint author), NIMH, Div AIDS Res, NIH, Bethesda, MD 20892 USA.
EM stirrattm@mail.nih.gov
OI Simoni, Jane/0000-0002-8711-1576
FU NIH Office of Behavioral and Social Sciences (OBSSR)
FX The paper is based in part on an NIH Adherence Network meeting on
"Advancing the Science of Adherence Assessment: A Working Meeting on
Self-Report Measures," sponsored by the NIH Office of Behavioral and
Social Sciences (OBSSR) and held 17 October 2011. We are grateful to
Shoshana Kahana for her contributions, to Janet de Moor, Martha Hare,
Donna McCloskey, and Anne Trontell for their paper feedback, and to all
members of the NIH Adherence Network for their support.
NR 135
TC 17
Z9 17
U1 8
U2 18
PU SPRINGER INTERNATIONAL PUBLISHING AG
PI CHAM
PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND
SN 1869-6716
EI 1613-9860
J9 TRANSL BEHAV MED
JI Transl. Behav. Med.
PD DEC
PY 2015
VL 5
IS 4
BP 470
EP 482
DI 10.1007/s13142-015-0315-2
PG 13
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA DC0LV
UT WOS:000368909700011
PM 26622919
ER
PT J
AU Riddle, M
AF Riddle, Melissa
CA Sci Behav Change Working Grp
TI News from the NIH: using an experimental medicine approach to facilitate
translational research
SO TRANSLATIONAL BEHAVIORAL MEDICINE
LA English
DT News Item
C1 [Riddle, Melissa; Sci Behav Change Working Grp] NIH, Bldg 10, Bethesda, MD 20892 USA.
RP Riddle, M (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA.
EM riddleme@mail.nih.gov
NR 4
TC 2
Z9 2
U1 3
U2 3
PU SPRINGER INTERNATIONAL PUBLISHING AG
PI CHAM
PA GEWERBESTRASSE 11, CHAM, CH-6330, SWITZERLAND
SN 1869-6716
EI 1613-9860
J9 TRANSL BEHAV MED
JI Transl. Behav. Med.
PD DEC
PY 2015
VL 5
IS 4
BP 486
EP 488
DI 10.1007/s13142-015-0333-0
PG 3
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA DC0LV
UT WOS:000368909700013
PM 26622921
ER
PT J
AU Tang, H
Fan, XQ
Xing, JY
Liu, ZY
Jiang, B
Dou, Y
Gorospe, M
Wang, WG
AF Tang, Hao
Fan, Xiuqin
Xing, Junyue
Liu, Zhenyun
Jiang, Bin
Dou, Yali
Gorospe, Myriam
Wang, Wengong
TI NSun2 delays replicative senescence by repressing p27 (KIP1) translation
and elevating CDK1 translation
SO AGING-US
LA English
DT Article
DE NSun2; p27KIP1; mRNA methylation; translational regulation; replicative
senescence
ID HUMAN-DIPLOID FIBROBLASTS; RIBOSOMAL-RNA METHYLATIONS; CYCLIN-DEPENDENT
KINASES; P27(KIP1) MESSENGER-RNA; CELL-CYCLE; ESCHERICHIA-COLI; REDUCED
EXPRESSION; CANCER; PROLIFERATION; INHIBITORS
AB A rise in the levels of the cyclin-dependent kinase (CDK) inhibitor p27(KIP1) is important for the growth arrest of senescent cells, but the mechanisms responsible for this increase are poorly understood. Here, we show that the tRNA methyltransferase NSun2 represses the expression of p27 in replicative senescence. NSun2 methylated the 5'-untranslated region (UTR) of p27 mRNA at cytosine C64 in vitro and in cells, thereby repressing the translation of p27. During replicative senescence, increased p27 protein levels were accompanied by decreased NSun2 protein levels. Knockdown of NSun2 in human diploid fibroblasts (HDFs) elevated p27 levels and reduced the expression of CDK1 (encoded by CDK1 mRNA, a previously reported target of NSun2), which in turn further repressed cell proliferation and accelerated replicative senescence, while overexpression of NSun2 exerted the opposite effect. Ectopic overexpression of the p27 5'UTR fragment rescued the effect of NSun2 overexpression in lowering p27, increasing CDK1, promoting cell proliferation, and delaying replicative senescence. Our findings indicate that NSun2-mediated mRNA methylation regulates p27 and CDK1 levels during replicative senescence.
C1 [Tang, Hao; Fan, Xiuqin; Xing, Junyue; Liu, Zhenyun; Jiang, Bin; Wang, Wengong] Peking Univ, Hlth Sci Ctr, Beijing Key Lab Prot Posttranslat Modificat & Cel, Dept Biochem & Mol Biol,Sch Basic Med Sci, Beijing 100191, Peoples R China.
[Dou, Yali] Univ Michigan, Dept Pathol & Biol Chem, MSI 5215A, Ann Arbor, MI 48105 USA.
[Gorospe, Myriam] NIA, Genet Lab, NIH, Baltimore, MD 21224 USA.
RP Wang, WG (reprint author), Peking Univ, Hlth Sci Ctr, Beijing Key Lab Prot Posttranslat Modificat & Cel, Dept Biochem & Mol Biol,Sch Basic Med Sci, Beijing 100191, Peoples R China.
EM wwg@bjmu.edu.cn
FU National Science Foundation of China [81230008, 81420108016, 91339114];
Ministry of Education of People's Republic of China [B07001]; NIA-IRP,
NIH
FX This work was supported by Grants 81230008, 81420108016, and 91339114
from the National Science Foundation of China; Grant B07001 (111
project) from the Ministry of Education of People's Republic of China.
M.G. was supported by the NIA-IRP, NIH.
NR 42
TC 5
Z9 5
U1 0
U2 0
PU IMPACT JOURNALS LLC
PI ALBANY
PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA
SN 1945-4589
J9 AGING-US
JI Aging-US
PD DEC
PY 2015
VL 7
IS 12
BP 1143
EP 1158
PG 16
WC Cell Biology
SC Cell Biology
GA DB5BU
UT WOS:000368528900013
PM 26687548
ER
PT J
AU Roman, TS
Marvelle, AF
Fogarty, MP
Vadlamudi, S
Gonzalez, AJ
Buchkovich, ML
Huyghe, JR
Fuchsberger, C
Jackson, AU
Wu, Y
Civelek, M
Lusis, AJ
Gaulton, KJ
Sethupathy, P
Kangas, AJ
Soininen, P
Ala-Korpela, M
Kuusisto, J
Collins, FS
Laakso, M
Boehnke, M
Mohlke, KL
AF Roman, Tamara S.
Marvelle, Amanda F.
Fogarty, Marie P.
Vadlamudi, Swarooparani
Gonzalez, Arlene J.
Buchkovich, Martin L.
Huyghe, Jeroen R.
Fuchsberger, Christian
Jackson, Anne U.
Wu, Ying
Civelek, Mete
Lusis, Aldons J.
Gaulton, Kyle J.
Sethupathy, Praveen
Kangas, Antti J.
Soininen, Pasi
Ala-Korpela, Mika
Kuusisto, Johanna
Collins, Francis S.
Laakso, Markku
Boehnke, Michael
Mohlke, Karen L.
TI Multiple Hepatic Regulatory Variants at the GALNT2 GWAS Locus Associated
with High-Density Lipoprotein Cholesterol
SO AMERICAN JOURNAL OF HUMAN GENETICS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; POLYPEPTIDE N-ACETYLGALACTOSAMINYLTRANSFERASE;
UPSTREAM STIMULATORY FACTOR; ALPHA-D-GALACTOSAMINE; C/EBP-BETA; LIPID
CONCENTRATIONS; ENDOTHELIAL LIPASE; O-GLYCOSYLATION; GENOTYPE DATA; CDNA
CLONING
AB Genome-wide association studies (GWASs) have identified more than 150 loci associated with blood lipid and cholesterol levels; however, the functional and molecular mechanisms for many associations are unknown. We examined the functional regulatory effects of candidate variants at the GALNT2 locus associated with high-density lipoprotein cholesterol (HDL-C). Fine-mapping and conditional analyses in the METSIM study identified a single locus harboring 25 noncoding variants (r(2) > 0.7 with the lead GWAS variants) strongly associated with total cholesterol in medium-sized HDL (e.g., rs17315646, p = 3.5 x 10(-12)). We used luciferase reporter assays in HepG2 cells to test all 25 variants for allelic differences in regulatory enhancer activity. rs2281721 showed allelic differences in transcriptional activity (75-fold [T] versus 27-fold [C] more than the empty-vector control), as did a separate 780-bp segment containing rs4846913, rs2144300, and rs6143660 (49-fold [AT(-) haplotype] versus 16-fold [CC+ haplotype] more). Using electrophoretic mobility shift assays, we observed differential CEBPB binding to rs4846913, and we confirmed this binding in a native chromatin context by performing chromatin-immunoprecipitation (ChIP) assays in HepG2 and Huh-7 cell lines of differing genotypes. Additionally, sequence reads in HepG2 DNase-I-hypersensitivity and CEBPB ChIP-seq signals spanning rs4846913 showed significant allelic imbalance. Allelic-expression-imbalance assays performed with RNA from primary human hepatocyte samples and expression-quantitative-trait-locus (eQTL) data in human subcutaneous adipose tissue samples confirmed that alleles associated with increased HDL-C are associated with a modest increase in GALNT2 expression. Together, these data suggest that at least rs4846913 and rs2281721 play key roles in influencing GALNT2 expression at this HDL-C locus.
C1 [Roman, Tamara S.; Marvelle, Amanda F.; Fogarty, Marie P.; Vadlamudi, Swarooparani; Gonzalez, Arlene J.; Buchkovich, Martin L.; Wu, Ying; Gaulton, Kyle J.; Sethupathy, Praveen; Mohlke, Karen L.] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA.
[Roman, Tamara S.] Univ N Carolina, Curriculum Genet & Mol Biol, Chapel Hill, NC 27599 USA.
[Huyghe, Jeroen R.; Fuchsberger, Christian; Jackson, Anne U.; Boehnke, Michael] Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48109 USA.
[Huyghe, Jeroen R.; Fuchsberger, Christian; Jackson, Anne U.; Boehnke, Michael] Univ Michigan, Sch Publ Hlth, Ctr Stat Genet, Ann Arbor, MI 48109 USA.
[Civelek, Mete; Lusis, Aldons J.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA.
[Civelek, Mete] Univ Virginia, Ctr Publ Hlth Genom, Dept Biomed Engn, Charlottesville, VA 22908 USA.
[Lusis, Aldons J.] Univ Calif Los Angeles, David Geffen Sch Med, Deparment Microbiol Immunol & Mol Genet, Los Angeles, CA 90095 USA.
[Lusis, Aldons J.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Human Genet, Los Angeles, CA 90095 USA.
[Gaulton, Kyle J.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England.
[Kangas, Antti J.; Soininen, Pasi; Ala-Korpela, Mika] Univ Oulu, Inst Hlth Sci, Computat Med, Oulu 90014, Finland.
[Soininen, Pasi; Ala-Korpela, Mika] Univ Eastern Finland, Sch Pharm, Nucl Magnet Resonance Metabol Lab, Kuopio 70211, Finland.
[Ala-Korpela, Mika] Oulu Univ Hosp, Oulu 90220, Finland.
[Ala-Korpela, Mika] Univ Bristol, Sch Social & Community Med, Computat Med, Bristol BS8 2BN, Avon, England.
[Ala-Korpela, Mika] Univ Bristol, MRC, Integrat Epidemiol Unit, Bristol BS8 2BN, Avon, England.
[Kuusisto, Johanna; Laakso, Markku] Univ Eastern Finland, Dept Med, Kuopio 70210, Finland.
[Kuusisto, Johanna; Laakso, Markku] Kuopio Univ Hosp, SF-70210 Kuopio, Finland.
[Collins, Francis S.] NHGRI, NIH, Bethesda, MD 20892 USA.
RP Mohlke, KL (reprint author), Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA.
EM mohlke@med.unc.edu
OI Fuchsberger, Christian/0000-0002-5918-8947; Civelek,
Mete/0000-0002-8141-0284
FU NIH [T32HL069768, T32GM007092, R01DK072193, R21DA027040, R01DK093757,
T32GM067553, R01DK062370, K99HL121172, P01HL28481]; National Human
Genome Research Institute Division of Intramural Research [Z01HG000024];
American Heart Association [13PRE16930025]; Academy of Finland [77299,
124243]; Finnish Heart Foundation; Finnish Diabetes Foundation; Finnish
Funding Agency for Technology and Innovation (TEKES) [1510/31/06];
Commission of the European Community [HEALTH-F2-2007-201681]; University
of Oulu; British Heart Foundation; Wellcome Trust; Medical Research
Council
FX This study was supported by NIH grants T32HL069768 (T.S.R.), T32GM007092
(T.S.R.), R01DK072193 (K.L.M.), R21DA027040 (K.L.M.), R01DK093757
(K.L.M.), T32GM067553 (M.L.B), R01DK062370 (M.B.), K99HL121172 (M.C.),
and P01HL28481 (A.J.L.) and National Human Genome Research Institute
Division of Intramural Research project number Z01HG000024 (F.S.C.);
American Heart Association Predoctoral Fellowship 13PRE16930025
(M.L.B.); Academy of Finland grants 77299 and 124243 (M.L.); the Finnish
Heart Foundation (M.L.); the Finnish Diabetes Foundation (M.L.); Finnish
Funding Agency for Technology and Innovation (TEKES) contract 1510/31/06
(M.L.); and Commission of the European Community HEALTH-F2-2007-201681
(M.L.). Applications and development of the quantitative-serum
nuclear-magnetic-resonance (NMR) metabolomics platform are supported by
the Academy of Finland, TEKES, Sigrid Juselius Foundation, Novo Nordisk
Foundation, and Finnish Diabetes Research Foundation. A.J.K., P.S., and
M.A.-K. are supported by the University of Oulu, British Heart
Foundation, Wellcome Trust, and Medical Research Council. Bristol Myers
Squibb supported the generation of METSIM microarray data. The authors
acknowledge the GoT2D Consortium for access to the reference panel used
for imputation; human organ donors whose liver samples were used in this
study; the ENCODE and NIH Roadmap Epigenomics Consortia, Data Analysis
and Coordination Centers, and production laboratories that generated the
chromatin, histone-modification, and chromatin-immunoprecipitation
(ChIP) sequencing data used for variant annotation. We thank Terry Furey
and Greg Crawford for interpretating ENCODE data, Jennifer Kulzer for
editing the manuscript, Yun Li and Qing Duan for providing 1000 Genomes
linkage-disequilibrium data, Scott Bultman and Dallas Donohoe for
providing advice on ChIP experiments, and Sumeet Khetarpal and Daniel
Rader for sharing unpublished results.
NR 64
TC 7
Z9 7
U1 0
U2 5
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 DEC
PY 2015
VL 97
IS 6
BP 801
EP 815
DI 10.1016/j.ajhg.2015.10.016
PG 15
WC Genetics & Heredity
SC Genetics & Heredity
GA DB3UM
UT WOS:000368437900003
PM 26637976
ER
PT J
AU O'Rawe, JA
Wu, YY
Dorfel, MJ
Rope, AF
Au, PYB
Parboosingh, JS
Moon, S
Kousi, M
Kosma, K
Smith, CS
Tzetis, M
Schuette, JL
Hufnagel, RB
Prada, CE
Martinez, F
Orellana, C
Crain, J
Caro-Llopis, A
Oltra, S
Monfort, S
Jimenez-Barron, LT
Swensen, J
Ellingwood, S
Smith, R
Fang, H
Ospina, S
Stegmann, S
Den Hollander, N
Mittelman, D
Highnam, G
Robison, R
Yang, E
Faivre, L
Roubertie, A
Riviere, JB
Monaghan, KG
Wang, K
Davis, EE
Katsanis, N
Kalscheuer, VM
Wang, EH
Metcalfe, K
Kleefstra, T
Innes, AM
Kitsiou-Tzeli, S
Rosello, M
Keegan, CE
Lyon, GJ
AF O'Rawe, Jason A.
Wu, Yiyang
Doerfel, Max J.
Rope, Alan F.
Au, P. Y. Billie
Parboosingh, Jillian S.
Moon, Sungjin
Kousi, Maria
Kosma, Konstantina
Smith, Christopher S.
Tzetis, Maria
Schuette, Jane L.
Hufnagel, Robert B.
Prada, Carlos E.
Martinez, Francisco
Orellana, Carmen
Crain, Jonathan
Caro-Llopis, Alfonso
Oltra, Silvestre
Monfort, Sandra
Jimenez-Barron, Laura T.
Swensen, Jeffrey
Ellingwood, Sara
Smith, Rosemarie
Fang, Han
Ospina, Sandra
Stegmann, Sander
Den Hollander, Nicolette
Mittelman, David
Highnam, Gareth
Robison, Reid
Yang, Edward
Faivre, Laurence
Roubertie, Agathe
Riviere, Jean-Baptiste
Monaghan, Kristin G.
Wang, Kai
Davis, Erica E.
Katsanis, Nicholas
Kalscheuer, Vera M.
Wang, Edith H.
Metcalfe, Kay
Kleefstra, Tjitske
Innes, A. Micheil
Kitsiou-Tzeli, Sophia
Rosello, Monica
Keegan, Catherine E.
Lyon, Gholson J.
TI TAF1 Variants Are Associated with Dysmorphic Features, Intellectual
Disability, and Neurological Manifestations
SO AMERICAN JOURNAL OF HUMAN GENETICS
LA English
DT Article
ID LINKED DYSTONIA-PARKINSONISM; DE-LANGE-SYNDROME; NEURON-SPECIFIC
ISOFORM; ACETYLTRANSFERASE ACTIVITY; TRANSCRIPTION; GENE; COMPLEX;
EXPRESSION; CORNELIA; DISEASE
AB We describe an X-linked genetic syndrome associated with mutations in TAF1 and manifesting with global developmental delay, intellectual disability (ID), characteristic facial dysmorphology, generalized hypotonia, and variable neurologic features, all in male individuals. Simultaneous studies using diverse strategies led to the identification of nine families with overlapping clinical presentations and affected by de novo or maternally inherited single-nucleotide changes. Two additional families harboring large duplications involving TAF1 were also found to share phenotypic overlap with the probands harboring single-nucleotide changes, but they also demonstrated a severe neurodegeneration phenotype. Functional analysis with RNA-seq for one of the families suggested that the phenotype is associated with downregulation of a set of genes notably enriched with genes regulated by E-box proteins. In addition, knockdown and mutant studies of this gene in zebrafish have shown a quantifiable, albeit small, effect on a neuronal phenotype. Our results suggest that mutations in TAF1 play a critical role in the development of this X-linked ID syndrome.
C1 [O'Rawe, Jason A.; Wu, Yiyang; Doerfel, Max J.; Crain, Jonathan; Jimenez-Barron, Laura T.; Fang, Han; Lyon, Gholson J.] Cold Spring Harbor Lab, Stanley Inst Cognit Genom, POB 100, Cold Spring Harbor, NY 11724 USA.
[O'Rawe, Jason A.; Wu, Yiyang; Lyon, Gholson J.] SUNY Stony Brook, Grad Program Genet, Stony Brook, NY 11794 USA.
[Rope, Alan F.] Northwest Kaiser Permanente, Dept Med Genet, Portland, OR 97227 USA.
[Au, P. Y. Billie; Parboosingh, Jillian S.; Smith, Christopher S.; Innes, A. Micheil] Univ Calgary, Dept Med Genet, Calgary, AB T3B 6A8, Canada.
[Au, P. Y. Billie; Parboosingh, Jillian S.; Smith, Christopher S.; Innes, A. Micheil] Univ Calgary, Alberta Childrens Hosp, Res Inst, Cumming Sch Med, Calgary, AB T3B 6A8, Canada.
[Moon, Sungjin; Kousi, Maria; Davis, Erica E.; Katsanis, Nicholas] Duke Univ, Ctr Human Dis Modeling, Durham, NC 27708 USA.
[Kosma, Konstantina; Tzetis, Maria; Kitsiou-Tzeli, Sophia] Univ Athens, Sch Med, Dept Med Genet, Athens 11527, Greece.
[Kosma, Konstantina; Tzetis, Maria] Childrens Hosp, Res Inst Study Genet & Malignant Disorders Childh, Aghia Sophia, Athens 11527, Greece.
[Schuette, Jane L.] Univ Michigan, Dept Pediat, Div Genet, Ann Arbor, MI 48109 USA.
[Schuette, Jane L.; Keegan, Catherine E.] Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA.
[Hufnagel, Robert B.; Prada, Carlos E.] Cincinnati Childrens Hosp, Div Human Genet, Cincinnati, OH 45229 USA.
[Hufnagel, Robert B.] NEI, Unit Pediat Dev & Genet Ophthalmol, Ophthalm Genet & Visual Funct Branch, NIH, Bethesda, MD 20892 USA.
[Prada, Carlos E.] Fdn Cardiovasc Colombia, Ctr Med Genom & Metab, Santander 681004, Colombia.
[Martinez, Francisco; Orellana, Carmen; Caro-Llopis, Alfonso; Oltra, Silvestre; Monfort, Sandra; Rosello, Monica] Hosp Univ & Politecn La Fe, Unidad Genet, Valencia 46026, Spain.
[Jimenez-Barron, Laura T.] Univ Nacl Autonoma Mexico, Ctr Ciencias Genom, Cuernavaca 62210, Morelos, Mexico.
[Swensen, Jeffrey] Caris Life Sci, Phoenix, AZ 85040 USA.
[Ellingwood, Sara] Maine Med Partners, Pediat Specialty Care, Div Genet, Portland, ME 04102 USA.
[Smith, Rosemarie] Barbara Bush Childrens Hosp, Maine Med Ctr, Dept Pediat, Div Genet, Portland, ME 04102 USA.
[Ospina, Sandra] Fdn Cardioinfantil, Bogota 681004, Colombia.
[Ospina, Sandra] Univ Rosario, Bogota 681004, Colombia.
[Stegmann, Sander] Dept Clin Genet, NL-6202 AZ Maastricht, Netherlands.
[Den Hollander, Nicolette] Leiden Univ, Med Ctr, Dept Clin Genet, NL-2300 RC Leiden, Netherlands.
[Mittelman, David; Highnam, Gareth] Gene Gene Ltd, Houston, TX 77008 USA.
[Robison, Reid; Lyon, Gholson J.] Utah Fdn Biomed Res, Salt Lake City, UT 84107 USA.
[Robison, Reid] Tute Genom, Provo, UT 84601 USA.
[Yang, Edward] Boston Childrens Hosp, Dept Radiol, Boston, MA 02115 USA.
[Faivre, Laurence; Riviere, Jean-Baptiste] Univ Bourgogne Franche Comte, Genet Anomalies Dev EA4271, F-21000 Dijon, France.
[Faivre, Laurence] CHU Dijon, Ctr Reference Malad Rares Anomalies Dev & Syndrom, Ctr Genet, F-21000 Dijon, France.
[Roubertie, Agathe] Univ Montpellier, Inst Neurosci Montpellier, F-34950 Montpellier 5, France.
[Roubertie, Agathe] CHU Gui de Chauliac, Serv Neuropediat, F-34000 Montpellier, France.
[Monaghan, Kristin G.] GeneDx, Gaithersburg, MD 20877 USA.
[Wang, Kai] Univ So Calif, Zilkha Neurogenet Inst, Dept Psychiat & Prevent Med, Los Angeles, CA 90089 USA.
[Kalscheuer, Vera M.] Max Planck Inst Mol Genet, Res Grp Dev & Dis, D-14195 Berlin, Germany.
[Wang, Edith H.] Univ Washington, Dept Pharmacol, Seattle, WA 98195 USA.
[Metcalfe, Kay] Cent Manchester Univ Hosp NHS Fdn Trust, St Marys Hosp, Manchester Ctr Genom Med, Clin Genet Serv, Manchester M13 9WL, Lancs, England.
[Kleefstra, Tjitske] Radboud Univ Nijmegen, Med Ctr, Dept Human Genet, NL-6500 HB Nijmegen, Netherlands.
RP Lyon, GJ (reprint author), Cold Spring Harbor Lab, Stanley Inst Cognit Genom, POB 100, Cold Spring Harbor, NY 11724 USA.
EM gholsonjlyon@gmail.com
RI Oltra, Silvestre/A-2697-2009; innes, allan micheil/A-9955-2017;
Martinez, Francisco/A-2543-2009
OI Oltra, Silvestre/0000-0001-6863-4382; Martinez,
Francisco/0000-0002-0589-2584
FU Stanley Institute for Cognitive Genomics at Cold Spring Harbor
Laboratory; NIH [HG006465]; Alberta Children's Hospital Foundation;
Instituto de Salud Carlos III Accion Estrategica en Salud [PI14/00350];
Netherlands Organization for Health Research and Development, ZonMw
[907-00-365]; Cincinnati Children's Hospital
FX G.J.L. is supported by funds from the Stanley Institute for Cognitive
Genomics at Cold Spring Harbor Laboratory. K.W. is supported by NIH
grant HG006465. The sequencing by Complete Genomics was provided by a
data-analysis grant to K.W. We would like to thank Megan Cho for
facilitating discovery of affected individuals through GeneDx. Margaret
Yoon and David Tegay assisted with Human Phenotype Ontology annotation.
A.M.I. and J.S.P. were supported by a grant from the Alberta Children's
Hospital Foundation and would like to thank Francois Bernier and Ryan
Lamont for helpful discussions and contributions. F.M., M.R., and
colleagues are supported by grant PI14/00350 (Instituto de Salud Carlos
III Accion Estrategica en Salud 2013-2016; Fondo Europeo de Desarrollo
Regional). This work was supported in part by funding from grants from
the Netherlands Organization for Health Research and Development, ZonMw
(grant 907-00-365 to T.K.), and an institutional award from Cincinnati
Children's Hospital (R.B.H.). N.K. is a distinguished George W. Brumley
Professor. The authors would like to thank the Exome Aggregation
Consortium and the groups that provided exome variant data for
comparison. A full list of contributing groups can be found at
http://exac.broadinstitute.org/about.
NR 56
TC 7
Z9 7
U1 1
U2 7
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 DEC
PY 2015
VL 97
IS 6
BP 922
EP 932
DI 10.1016/j.ajhg.2015.11.005
PG 11
WC Genetics & Heredity
SC Genetics & Heredity
GA DB3UM
UT WOS:000368437900015
PM 26637982
ER
PT J
AU Corren, J
Togias, A
AF Corren, Jonathan
Togias, Alkis
TI Remodeling in Allergic Rhinitis Adding New Data to an Old Debate
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Editorial Material
ID ASTHMA; AIRWAYS
C1 [Corren, Jonathan] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA.
[Togias, Alkis] NIAID, Div Allergy Immunol & Transplantat, Bethesda, MD 20892 USA.
RP Corren, J (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA.
NR 13
TC 0
Z9 0
U1 1
U2 1
PU AMER THORACIC SOC
PI NEW YORK
PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA
SN 1073-449X
EI 1535-4970
J9 AM J RESP CRIT CARE
JI Am. J. Respir. Crit. Care Med.
PD DEC
PY 2015
VL 192
IS 12
BP 1403
EP 1404
PG 2
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA DB3RT
UT WOS:000368429700002
PM 26669466
ER
PT J
AU Lam, S
Szabo, E
AF Lam, Stephen
Szabo, Eva
TI Preinvasive Endobronchial Lesions: Lung Cancer Precursors and Risk
Markers?
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Editorial Material
ID AUTOFLUORESCENCE BRONCHOSCOPY; BRONCHIAL EPITHELIUM; DYSPLASIA;
CARCINOMA; SMOKERS
C1 [Lam, Stephen] British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada.
Univ British Columbia, Vancouver, BC V5Z 1M9, Canada.
NCI, NIH, Rockville, MD USA.
RP Lam, S (reprint author), British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada.
NR 20
TC 3
Z9 3
U1 0
U2 0
PU AMER THORACIC SOC
PI NEW YORK
PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA
SN 1073-449X
EI 1535-4970
J9 AM J RESP CRIT CARE
JI Am. J. Respir. Crit. Care Med.
PD DEC
PY 2015
VL 192
IS 12
BP 1411
EP 1413
PG 4
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA DB3RT
UT WOS:000368429700007
PM 26669471
ER
PT J
AU Boyer, PL
Das, K
Arnold, E
Hughes, SH
AF Boyer, Paul L.
Das, Kalyan
Arnold, Eddy
Hughes, Stephen H.
TI Analysis of the Zidovudine Resistance Mutations T215Y, M41L, and L210W
in HIV-1 Reverse Transcriptase
SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; HIGH-LEVEL RESISTANCE; DRUG-RESISTANCE;
T-LYMPHOCYTES; MOLECULAR-MECHANISMS; SELECTIVE EXCISION; AZT RESISTANCE;
DE-NOVO; INHIBITORS; ASSOCIATION
AB Although anti-human immunodeficiency virus type 1 (HIV-1) therapies have become more sophisticated and more effective, drug resistance continues to be a major problem. Zidovudine (azidothymidine; AZT) was the first nucleoside reverse transcriptase (RT) inhibitor (NRTI) approved for the treatment of HIV-1 infections and is still being used, particularly in the developing world. This drug targets the conversion of single-stranded RNA to double-stranded DNA by HIV-1 RT. However, resistance to the drug quickly appeared both in viruses replicating in cells in culture and in patients undergoing AZT monotherapy. The primary resistance pathway selects for mutations of T215 that change the threonine to either a tyrosine or a phenylalanine (T215Y/F); this resistance pathway involves an ATP-dependent excision mechanism. The pseudo-sugar ring of AZT lacks a 3' OH; RT incorporates AZT monophosphate (AZTMP), which blocks the end of the viral DNA primer. AZT-resistant forms of HIV-1 RT use ATP in an excision reaction to unblock the 3' end of the primer strand, allowing its extension by RT. The T215Y AZT resistance mutation is often accompanied by two other mutations, M41L and L210W. In this study, the roles of these mutations, in combination with T215Y, were examined to determine whether they affect polymerization and excision by HIV-1 RT. The M41L mutation appears to help restore the DNA polymerization activity of RT containing the T215Y mutation and also enhances AZTMP excision. The L210W mutation plays a similar role, but it enhances excision by RTs that carry the T215Y mutation when ATP is present at a low concentration.
C1 [Boyer, Paul L.; Hughes, Stephen H.] NCI, HIV Dynam & Replicat Program, NIH, Frederick, MD 21701 USA.
[Das, Kalyan; Arnold, Eddy] Rutgers State Univ, Ctr Adv Biotechnol & Med, Piscataway, NJ 08854 USA.
[Das, Kalyan; Arnold, Eddy] Rutgers State Univ, Dept Chem & Chem Biol, Piscataway, NJ USA.
RP Hughes, SH (reprint author), NCI, HIV Dynam & Replicat Program, NIH, Frederick, MD 21701 USA.
EM hughesst@mail.nih.gov
FU Intramural Research Program of the NIH, NCI-Frederick; NIH [R37
AI027690]
FX This research was supported by the Intramural Research Program of the
NIH, NCI-Frederick. E.A. is grateful to NIH merit award R37 AI027690 for
support.
NR 34
TC 1
Z9 1
U1 0
U2 10
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0066-4804
EI 1098-6596
J9 ANTIMICROB AGENTS CH
JI Antimicrob. Agents Chemother.
PD DEC
PY 2015
VL 59
IS 12
BP 7184
EP 7196
DI 10.1128/AAC.05069-14
PG 13
WC Microbiology; Pharmacology & Pharmacy
SC Microbiology; Pharmacology & Pharmacy
GA DB2KO
UT WOS:000368337300004
PM 26324274
ER
PT J
AU Levendosky, K
Mizenina, O
Martinelli, E
Jean-Pierre, N
Kizima, L
Rodriguez, A
Kleinbeck, K
Bonnaire, T
Robbiani, M
Zydowsky, TM
O'Keefe, BR
Fernandez-Romero, JA
AF Levendosky, Keith
Mizenina, Olga
Martinelli, Elena
Jean-Pierre, Ninochka
Kizima, Larisa
Rodriguez, Aixa
Kleinbeck, Kyle
Bonnaire, Thierry
Robbiani, Melissa
Zydowsky, Thomas M.
O'Keefe, Barry R.
Fernandez-Romero, Jose A.
TI Griffithsin and Carrageenan Combination To Target Herpes Simplex Virus 2
and Human Papillomavirus
SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
LA English
DT Article
ID ENTRY INHIBITOR GRIFFITHSIN; TO-CELL SPREAD; GLYCOPROTEIN-D; IN-VITRO;
VAGINAL MICROBICIDE; SOUTH-AFRICA; INFECTION; RECEPTOR; VIVO;
IDENTIFICATION
AB Extensive preclinical evaluation of griffithsin (GRFT) has identified this lectin to be a promising broad-spectrum microbicide. We set out to explore the antiviral properties of a GRFT and carrageenan (CG) combination product against herpes simplex virus 2 (HSV-2) and human papillomavirus (HPV) as well as determine the mechanism of action (MOA) of GRFT against both viruses. We performed the experiments in different cell lines, using time-of-addition and temperature dependence experiments to differentiate inhibition of viral attachment from entry and viral receptor internalization. Surface plasmon resonance (SPR) was used to assess GRFT binding to viral glycoproteins, and immunoprecipitation and immunohistochemistry were used to identify the specific glycoprotein involved. We determined the antiviral activity of GRFT against HSV-2 to be a 50% effective concentration (EC50) of 230 nM and provide the first evidence that GRFT has moderate anti-HPV activity (EC50 = 0.429 to 1.39 mu M). GRFT blocks the entry of HSV-2 and HPV into target cells but not the adsorption of HSV-2 and HPV onto target cells. The results of the SPR, immunoprecipitation, and immunohistochemistry analyses of HSV-2 combined suggest that GRFT may block viral entry by binding to HSV-2 glycoprotein D. Cell-based assays suggest anti-HPV activity through alpha(6) integrin internalization. The GRFT-CG combination product but not GRFT or CG alone reduced HSV-2 vaginal infection in mice when given an hour before challenge (P = 0.0352). While GRFT significantly protected mice against vaginal HPV infection when dosed during and after HPV16 pseudovirus challenge (P < 0.026), greater CG-mediated protection was afforded by the GRFT-CG combination for up to 8 h (P < 0.0022). These findings support the development of the GRFT-CG combination as a broad-spectrum microbicide.
C1 [Levendosky, Keith; Mizenina, Olga; Martinelli, Elena; Jean-Pierre, Ninochka; Kizima, Larisa; Rodriguez, Aixa; Kleinbeck, Kyle; Bonnaire, Thierry; Robbiani, Melissa; Zydowsky, Thomas M.; Fernandez-Romero, Jose A.] Populat Council, Ctr Biomed Res, New York, NY 10021 USA.
[O'Keefe, Barry R.] NCI, Mol Targets Lab, Ctr Canc Res, Frederick, MD 21701 USA.
RP Fernandez-Romero, JA (reprint author), Populat Council, Ctr Biomed Res, 1230 York Ave, New York, NY 10021 USA.
EM jromero@popcouncil.org
FU U.S. Agency for International Development (USAID) [GPO A 00 04 00019
00]; NIH, National Cancer Institute, Center for Cancer Research
FX This research has been supported by the President's Emergency Plan for
AIDS Relief (PEPFAR) through the U.S. Agency for International
Development (USAID) under the terms of GPO A 00 04 00019 00. This
research was also supported by the Intramural Research Program of the
NIH, National Cancer Institute, Center for Cancer Research (to B.R.O.).
NR 46
TC 4
Z9 4
U1 3
U2 6
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0066-4804
EI 1098-6596
J9 ANTIMICROB AGENTS CH
JI Antimicrob. Agents Chemother.
PD DEC
PY 2015
VL 59
IS 12
BP 7290
EP 7298
DI 10.1128/AAC.01816-15
PG 9
WC Microbiology; Pharmacology & Pharmacy
SC Microbiology; Pharmacology & Pharmacy
GA DB2KO
UT WOS:000368337300016
PM 26369967
ER
PT J
AU Yaniv, Y
Lakatta, EG
AF Yaniv, Yael
Lakatta, Edward G.
TI The end effector of circadian heart rate variation: the sinoatrial node
pacemaker cell
SO BMB REPORTS
LA English
DT Review
DE Cardiac denervation; Coupled-clock pacemaker system; Fractal-like
behavior; Heart rate variability; Ultradian rhythm of the heart rate
ID CARDIOMYOCYTE MOLECULAR CLOCK; POWER-LAW BEHAVIOR; RATE-VARIABILITY;
SUPRACHIASMATIC NUCLEUS; ARRHYTHMIA SUSCEPTIBILITY;
CARDIOVASCULAR-DISEASE; BLOOD-PRESSURE; RHYTHMS; MODULATION; MECHANISMS
AB Cardiovascular function is regulated by the rhythmicity of circadian, infradian and ultradian clocks. Specific time scales of different cell types drive their functions: circadian gene regulation at hours scale, activation-inactivation cycles of ion channels at millisecond scales, the heart's beating rate at hundreds of millisecond scales, and low frequency autonomic signaling at cycles of tens of seconds. Heart rate and rhythm are modulated by a hierarchical clock system: autonomic signaling from the brain releases neurotransmitters from the vagus and sympathetic nerves to the heart's pacemaker cells and activate receptors on the cell. These receptors activating ultradian clock functions embedded within pacemaker cells include sarcoplasmic reticulum rhythmic spontaneous Ca2+ cycling, rhythmic ion channel current activation and inactivation, and rhythmic oscillatory mitochondria ATP production. Here we summarize the evidence that intrinsic pacemaker cell mechanisms are the end effector of the hierarchical brain-heart circadian clock system.
C1 [Yaniv, Yael] Technion Israel Inst Technol, Biomed Engn Fac, Haifa, Israel.
[Lakatta, Edward G.] NIA, Cardiovasc Sci Lab, Biomed Res Ctr, Intramural Res Program,NIH, Baltimore, MD 21224 USA.
RP Yaniv, Y (reprint author), Technion Israel Inst Technol, Biomed Engn Fac, 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-Krbling Biomedical Engineering Research Fund
FX This research was partially supported by the Intramural Research Program
of the NIH, National Institute on Aging and by Technion V.P.R
Fund-Krbling Biomedical Engineering Research Fund (Y.Y).
NR 69
TC 2
Z9 2
U1 7
U2 14
PU KOREAN SOCIETY BIOCHEMISTRY & MOLECULAR BIOLOGY
PI SEOUL
PA KOREA SCIENCE & TECHNOLOGY CENTER, # 801, 635-4 , YEOKSAM-DONG,
KANGNAM-KU, SEOUL, 135-703, SOUTH KOREA
SN 1976-6696
EI 1976-670X
J9 BMB REP
JI BMB Rep.
PD DEC
PY 2015
VL 48
IS 12
BP 677
EP 684
DI 10.5483/BMBRep.2015.48.12.061
PG 8
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA DB4VE
UT WOS:000368510900006
PM 25999176
ER
PT J
AU Fox, A
Jeffrey, B
Hasni, S
Nussenblatt, R
Sen, HN
AF Fox, Austin
Jeffrey, Brett
Hasni, Sarfaraz
Nussenblatt, Robert
Sen, H. Nida
TI Rituximab treatment for nonparaneoplastic autoimmune retinopathy
SO CANADIAN JOURNAL OF OPHTHALMOLOGY-JOURNAL CANADIEN D OPHTALMOLOGIE
LA English
DT Letter
ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; RETINAL VASCULITIS; EFFICACY; SAFETY
C1 [Fox, Austin; Jeffrey, Brett; Nussenblatt, Robert; Sen, H. Nida] NEI, NIH, Bethesda, MD 20892 USA.
[Hasni, Sarfaraz; Nussenblatt, Robert; Sen, H. Nida] NIAMSD, NIH, Bethesda, MD 20892 USA.
RP Sen, HN (reprint author), NEI, NIH, Bethesda, MD 20892 USA.
EM senh@nei.nih.gov
FU Howard Hughes Medical Institute; Intramural NIH HHS
NR 14
TC 1
Z9 1
U1 0
U2 0
PU CANADIAN OPHTHAL SOC
PI OTTAWA
PA 1525 CARLING AVE SUITE 610, OTTAWA, ONTARIO K1Z 8R9, CANADA
SN 0008-4182
EI 1715-3360
J9 CAN J OPHTHALMOL
JI Can. J. Opthalmol.-J. Can. Opthalmol.
PD DEC
PY 2015
VL 50
IS 6
BP E101
EP E104
DI 10.1016/j.jcjo.2015.08.009
PG 4
WC Ophthalmology
SC Ophthalmology
GA DB2RA
UT WOS:000368355500001
PM 26651312
ER
PT J
AU Sotillo, E
Barrett, DM
Black, KL
Bagashev, A
Oldridge, D
Wu, G
Sussman, R
Lanauze, C
Ruella, M
Gazzara, MR
Martinez, NM
Harrington, CT
Chung, EY
Perazzelli, J
Hofmann, TJ
Maude, SL
Raman, P
Barrera, A
Gill, S
Lacey, SF
Melenhorst, JJ
Allman, D
Jacoby, E
Fry, T
Mackall, C
Barash, Y
Lynch, KW
Maris, JM
Grupp, SA
Thomas-Tikhonenko, A
AF Sotillo, Elena
Barrett, David M.
Black, Kathryn L.
Bagashev, Asen
Oldridge, Derek
Wu, Glendon
Sussman, Robyn
Lanauze, Claudia
Ruella, Marco
Gazzara, Matthew R.
Martinez, Nicole M.
Harrington, Colleen T.
Chung, Elaine Y.
Perazzelli, Jessica
Hofmann, Ted J.
Maude, Shannon L.
Raman, Pichai
Barrera, Alejandro
Gill, Saar
Lacey, Simon F.
Melenhorst, Jan J.
Allman, David
Jacoby, Elad
Fry, Terry
Mackall, Crystal
Barash, Yoseph
Lynch, Kristen W.
Maris, John M.
Grupp, Stephan A.
Thomas-Tikhonenko, Andrei
TI Convergence of Acquired Mutations and Alternative Splicing of CD19
Enables Resistance to CART-19 Immunotherapy
SO CANCER DISCOVERY
LA English
DT Article
ID ACUTE LYMPHOBLASTIC-LEUKEMIA; B-CELL DEVELOPMENT; PRE-MESSENGER-RNA;
MODIFIED T-CELLS; MYC; CHROMATIN; PROTEINS; PATHWAY; BINDING; WEB
AB The CD19 antigen, expressed on most B-cell acute lymphoblastic leukemias (B-ALL), can be targeted with chimeric antigen receptor-armed T cells (CART-19), but relapses with epitope loss occur in 10% to 20% of pediatric responders. We detected hemizygous deletions spanning the CD19 locus and de novo frameshift and missense mutations in exon 2 of CD19 in some relapse samples. However, we also discovered alternatively spliced CD19 mRNA species, including one lacking exon 2. Pull-down/siRNA experiments identified SRSF3 as a splicing factor involved in exon 2 retention, and its levels were lower in relapsed B-ALL. Using genome editing, we demonstrated that exon 2 skipping bypasses exon 2 mutations in B-ALL cells and allows expression of the N-terminally truncated CD19 variant, which fails to trigger killing by CART-19 but partly rescues defects associated with CD19 loss. Thus, this mechanism of resistance is based on a combination of deleterious mutations and ensuing selection for alternatively spliced RNA isoforms.
SIGNIFICANCE: CART-19 yield 70% response rates in patients with B-ALL, but also produce escape variants. We discovered that the underlying mechanism is the selection for preexisting alternatively spliced CD19 isoforms with the compromised CART-19 epitope. This mechanism suggests a possibility of targeting alternative CD19 ectodomains, which could improve survival of patients with B-cell neoplasms. (C) 2015 AACR.
C1 [Sotillo, Elena; Black, Kathryn L.; Bagashev, Asen; Wu, Glendon; Lanauze, Claudia; Harrington, Colleen T.; Chung, Elaine Y.; Raman, Pichai; Thomas-Tikhonenko, Andrei] Childrens Hosp Philadelphia, Div Canc Pathobiol, Philadelphia, PA 19104 USA.
[Barrett, David M.; Oldridge, Derek; Sussman, Robyn; Perazzelli, Jessica; Hofmann, Ted J.; Maude, Shannon L.; Raman, Pichai; Maris, John M.; Grupp, Stephan A.] Childrens Hosp Philadelphia, Div Oncol, Philadelphia, PA 19104 USA.
[Wu, Glendon; Thomas-Tikhonenko, Andrei] Univ Penn, Perelman Sch Med, Immunol Grad Grp, Philadelphia, PA 19104 USA.
[Lanauze, Claudia; Harrington, Colleen T.; Thomas-Tikhonenko, Andrei] Univ Penn, Perelman Sch Med, Cell & Mol Biol Grad Grp, Philadelphia, PA 19104 USA.
[Ruella, Marco; Gill, Saar] Univ Penn, Perelman Sch Med, Ctr Cellular Immunotherapies, Philadelphia, PA 19104 USA.
[Gazzara, Matthew R.; Barrera, Alejandro; Barash, Yoseph] Univ Penn, Perelman Sch Med, Dept Genet, Philadelphia, PA 19104 USA.
[Gazzara, Matthew R.; Martinez, Nicole M.; Lynch, Kristen W.] Univ Penn, Perelman Sch Med, Dept Biochem & Biophys, Philadelphia, PA 19104 USA.
[Gill, Saar; Lacey, Simon F.; Melenhorst, Jan J.] Univ Penn, Perelman Sch Med, Dept Med, Philadelphia, PA 19104 USA.
[Allman, David; Thomas-Tikhonenko, Andrei] Univ Penn, Perelman Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA.
[Jacoby, Elad; Fry, Terry; Mackall, Crystal] NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA.
RP Thomas-Tikhonenko, A (reprint author), Univ Penn, Childrens Hosp Philadelphia, 4056 Colket Translat Res Bldg,3501 Civ Ctr Blvd, Philadelphia, PA 19104 USA.
EM andreit@mail.med.upenn.edu
RI Thomas-Tikhonenko, Andrei/E-5329-2011
OI Thomas-Tikhonenko, Andrei/0000-0002-2739-2206
FU V Foundation for Cancer Research; William Lawrence and Blanche Hughes
Foundation; Leukemia & Lymphoma Society; Alex's Lemonade Stand
Foundation; NIH [R01 CA102709, T32 GM007229, T32 HL007439]; Stand Up To
Cancer St. Baldrick's Pediatric Dream Team Translational Research Grant
[SU2C-AACR-DT1113]
FX This work was supported by the V Foundation for Cancer Research, the
William Lawrence and Blanche Hughes Foundation, the Leukemia & Lymphoma
Society, the Alex's Lemonade Stand Foundation, the NIH (grants R01
CA102709, T32 GM007229 "Training Program in Cell and Molecular Biology,"
and T32 HL007439 "Hematology Clinical Research Training Program"), and
Stand Up To Cancer St. Baldrick's Pediatric Dream Team Translational
Research Grant SU2C-AACR-DT1113. Stand Up To Cancer is a program of the
Entertainment Industry Foundation administered by the American
Association for Cancer Research.
NR 49
TC 45
Z9 46
U1 2
U2 15
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 2159-8274
EI 2159-8290
J9 CANCER DISCOV
JI Cancer Discov.
PD DEC
PY 2015
VL 5
IS 12
BP 1282
EP 1295
DI 10.1158/2159-8290.CD-15-1020
PG 14
WC Oncology
SC Oncology
GA DB5TW
UT WOS:000368577500024
PM 26516065
ER
PT J
AU Joe, AK
Schnoll-Sussman, F
Bresalier, RS
Abrams, JA
Hibshoosh, H
Cheung, K
Friedman, RA
Yang, CS
Milne, GL
Liu, DD
Lee, JJ
Abdul, K
Bigg, M
Foreman, J
Su, T
Wang, XM
Ahmed, A
Neugut, AI
Akpa, E
Lippman, SM
Perloff, M
Brown, PH
Lightdale, CJ
AF Joe, Andrew K.
Schnoll-Sussman, Felice
Bresalier, Robert S.
Abrams, Julian A.
Hibshoosh, Hanina
Cheung, Ken
Friedman, Richard A.
Yang, Chung S.
Milne, Ginger L.
Liu, Diane D.
Lee, J. Jack
Abdul, Kazeem
Bigg, Michelle
Foreman, Jessica
Su, Tao
Wang, Xiaomei
Ahmed, Aqeel
Neugut, Alfred I.
Akpa, Esther
Lippman, Scott M.
Perloff, Marjorie
Brown, Powel H.
Lightdale, Charles J.
TI Phase Ib Randomized, Double-Blinded, Placebo-Controlled, Dose Escalation
Study of Polyphenon E in Patients with Barrett's Esophagus
SO CANCER PREVENTION RESEARCH
LA English
DT Article
ID MAJOR URINARY METABOLITE; GREEN TEA EXTRACTS; INTRAEPITHELIAL NEOPLASIA;
CONTROLLED TRIAL; PROSTATE-CANCER; BREAST-CANCER; PGE-M; PROSTAGLANDIN;
PHARMACOKINETICS; CARCINOGENESIS
AB This study was conducted to determine the safety and efficacy of the green tea-derived Polyphenon E (Poly E) in patients with Barrett's Esophagus (BE). Subjects were randomized to a 6-month, twice daily (BID) oral treatment of placebo or Poly E (200, 400, or 600 mg). Endoscopic evaluation, including biopsies, was performed before and after treatment. The primary objective was to demonstrate safety; secondary objectives investigated catechin accumulation and effects in clinical specimens. Of the 44 enrolled subjects, 11 received placebo, and 33 received Poly E. No dose-limiting toxicities were encountered, and a maximum tolerated dose (MTD) was not reached. The recommended phase II dose was 600 mg twice daily. The most common treatment-related adverse events (AE) in Poly E-treated subjects were grade I and II nausea, grade I belching, and grade I lactate dehydrogenase (LDH) elevation. No treatment-related AEs were reported in placebo-treated subjects, aside from grade I laboratory abnormalities. Pill counts and subject diaries were not consistently collected, and compliance was difficult to determine. However, on the basis of an intention-to-treat analysis, there was a significant relationship between Poly E dose and esophageal EGCG level-mean changes (pmol/g) of 0.79 (placebo), 6.06 (200 mg), 35.67 (400 mg), and 34.95 (600 mg); P = 0.005. There was a possible relationship between Poly E dose and urine PGE-M concentration. In conclusion, Poly E was well-tolerated, and treatment with Poly E (400 and 600 mg) but not Poly E (200 mg) or placebo resulted in clinically relevant and detectable EGCG accumulation in the target organ, esophageal mucosa. (C) 2015 AACR.
C1 [Joe, Andrew K.; Abrams, Julian A.; Neugut, Alfred I.; Lightdale, Charles J.] Columbia Univ, Med Ctr, Dept Med, New York, NY 10032 USA.
[Schnoll-Sussman, Felice; Bigg, Michelle] Weill Cornell Med Ctr, Dept Med, New York, NY USA.
[Bresalier, Robert S.; Foreman, Jessica] Univ Texas MD Anderson Canc Ctr, Gastroenterol Hepatol & Nutr, Houston, TX 77030 USA.
[Hibshoosh, Hanina] Columbia Univ, Med Ctr, Dept Pathol & Cell Biol, New York, NY 10032 USA.
[Cheung, Ken; Friedman, Richard A.; Abdul, Kazeem; Su, Tao; Wang, Xiaomei; Ahmed, Aqeel] Columbia Univ, Med Ctr, Herbert Irving Comprehens Canc Ctr, New York, NY 10032 USA.
[Yang, Chung S.] Rutgers State Univ, Dept Chem Biol, Piscataway, NJ USA.
[Milne, Ginger L.] Vanderbilt Univ, Div Clin Pharmacol, Brentwood, TN USA.
[Liu, Diane D.; Lee, J. Jack] Univ Texas MD Anderson Canc Ctr, Dept Biostat, Houston, TX 77030 USA.
[Akpa, Esther; Brown, Powel H.] Univ Texas MD Anderson Canc Ctr, Dept Clin Canc Prevent, Houston, TX 77030 USA.
[Lippman, Scott M.] Univ Calif San Diego, Moores Canc Ctr, La Jolla, CA 92093 USA.
[Perloff, Marjorie] NCI, Canc Prevent Div, Rockville, MD USA.
RP Joe, AK (reprint author), Columbia Univ, Coll Phys & Surg, Dept Med, 177 Ft Washington Ave, New York, NY 10032 USA.
EM akj3@cumc.columbia.edu
RI Milne, Ginger/D-7648-2014
OI Milne, Ginger/0000-0003-3890-151X
FU National Cancer Institute Division of Cancer Prevention NCI, DCP
Contract [N01 CN 035159]
FX This trial was supported by the National Cancer Institute Division of
Cancer Prevention NCI, DCP Contract N01 CN 035159 to the UTMD Anderson
Early Phase Chemoprevention Consortium.
NR 27
TC 4
Z9 4
U1 1
U2 5
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1940-6207
EI 1940-6215
J9 CANCER PREV RES
JI Cancer Prev. Res.
PD DEC
PY 2015
VL 8
IS 12
BP 1131
EP 1137
DI 10.1158/1940-6207.CAPR-14-0274-T
PG 7
WC Oncology
SC Oncology
GA DB5BS
UT WOS:000368528700001
PM 26471236
ER
PT J
AU Fabian, CJ
Kimler, BF
Zalles, CM
Phillips, TA
Metheny, T
Petroff, BK
Havighurst, TC
Kim, K
Bailey, HH
Heckman-Stoddard, BM
AF Fabian, Carol J.
Kimler, Bruce F.
Zalles, Carola M.
Phillips, Teresa A.
Metheny, Trina
Petroff, Brian K.
Havighurst, Thomas C.
Kim, KyungMann
Bailey, Howard H.
Heckman-Stoddard, Brandy M.
TI Clinical Trial of Acolbifene in Premenopausal Women at High Risk for
Breast Cancer
SO CANCER PREVENTION RESEARCH
LA English
DT Article
ID ESTROGEN-RECEPTOR MODULATORS; FINE-NEEDLE-ASPIRATION; LOW-DOSE
TAMOXIFEN; QUALITY-OF-LIFE; POSTMENOPAUSAL WOMEN; MAMMARY-GLAND;
ANTIESTROGEN EM-800; OVARIAN CYSTS; TREATED WOMEN; PURE SERM
AB The purpose of this study was to assess the feasibility of using the selective estrogen receptor modulator (SERM) acolbifene as a breast cancer prevention agent in premenopausal women. To do so, we assessed change in proliferation in benign breast tissue sampled by randomperiareolar fine-needle aspiration (RPFNA) as a primary endpoint, along with changes in other risk biomarkers and objective and subjective side effects as secondary endpoints. Twenty-five women with cytologic hyperplasia +/- atypia and >= 2% of breast epithelial cells staining positive for Ki-67, received 20 mg acolbifene daily for 6-8months, and then had benign breast tissue and blood risk biomarkers reassessed. Ki-67 decreased from a median of 4.6% [ interquartile range (IQR), 3.1%-8.5%] at baseline to 1.4% (IQR, 0.6%-3.5%) after acolbifene (P < 0.001; Wilcoxon signed-rank test), despite increases in bioavailable estra-diol. There were also significant decreases in expression (RT-qPCR) of estrogen-inducible genes that code for pS2, ERa, and progesterone receptor (P <= 0.026). There was no significant change in serumIGF1, IGFBP3, IGF1: IGFBP3 ratio, ormammographic breast density. Subjective side effects were minimal with no significant increase in hot flashes, muscle cramps, arthralgias, or fatigue. Objective measures showed a clinically insignificant decrease in lumbar spinebone density (DEXA) and an increase in ovarian cysts but no change in endometrial thickness (sonography). In summary, acolbifene was associated with favorable changes in benign breast epithelial cell proliferation and estrogen-inducible gene expression but minimal side effects, suggesting a phase IIB placebo- controlled trial evaluating it further for breast cancer prevention. (C) 2015 AACR.
C1 [Fabian, Carol J.; Phillips, Teresa A.; Metheny, Trina; Petroff, Brian K.] Univ Kansas, Med Ctr, Dept Internal Med, Kansas City, KS 66160 USA.
[Kimler, Bruce F.] Univ Kansas, Med Ctr, Dept Radiat Oncol, Kansas City, KS 66160 USA.
[Zalles, Carola M.] Mercy Hosp, Miami, FL USA.
[Havighurst, Thomas C.; Kim, KyungMann] Univ Wisconsin, Dept Biostat & Med Informat, Madison, WI USA.
[Bailey, Howard H.] Univ Wisconsin, Carbone Canc Ctr, Madison, WI USA.
[Heckman-Stoddard, Brandy M.] NCI, Canc Prevent Div, Bethesda, MD 20892 USA.
RP Kimler, BF (reprint author), Univ Kansas, Med Ctr, 3901 Rainbow Blvd, Kansas City, KS 66160 USA.
EM bkimler@kumc.edu
FU University of Wisconsin Cancer Consortium for "Phase I and Phase II
Clinical Trials of Cancer Chemopreventive Agents" [938N232]; NCI, NIH
[NO1-CN-35153]
FX This study was supported by Subcontract 938N232 from the University of
Wisconsin Cancer Consortium for "Phase I and Phase II Clinical Trials of
Cancer Chemopreventive Agents" (PI: H.H. Bailey, MD) and NO1-CN-35153,
NCI, NIH.
NR 59
TC 0
Z9 0
U1 0
U2 1
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1940-6207
EI 1940-6215
J9 CANCER PREV RES
JI Cancer Prev. Res.
PD DEC
PY 2015
VL 8
IS 12
BP 1146
EP 1155
DI 10.1158/1940-6207.CAPR-15-0109
PG 10
WC Oncology
SC Oncology
GA DB5BS
UT WOS:000368528700003
PM 26391916
ER
PT J
AU Petrick, JL
Sahasrabuddhe, VV
Chan, AT
Alavanja, MC
Beane-Freeman, LE
Buring, JE
Chen, J
Chong, DQ
Freedman, ND
Fuchs, CS
Gaziano, JM
Giovannucci, E
Graubard, BI
Hollenbeck, AR
Hou, LF
Jacobs, EJ
King, LY
Koshiol, J
Lee, IM
Linet, MS
Palmer, JR
Purdue, MP
Rosenberg, L
Schairer, C
Sesso, HD
Sigurdson, AJ
Wactawski-Wende, J
Zeleniuch-Jacquotte, A
Campbell, PT
McGlynn, KA
AF Petrick, Jessica L.
Sahasrabuddhe, Vikrant V.
Chan, Andrew T.
Alavanja, Michael C.
Beane-Freeman, Laura E.
Buring, Julie E.
Chen, Jie
Chong, Dawn Q.
Freedman, Neal D.
Fuchs, Charles S.
Michael Gaziano, John
Giovannucci, Edward
Graubard, Barry I.
Hollenbeck, Albert R.
Hou, Lifang
Jacobs, Eric J.
King, Lindsay Y.
Koshiol, Jill
Lee, I-Min
Linet, Martha S.
Palmer, Julie R.
Purdue, Mark P.
Rosenberg, Lynn
Schairer, Catherine
Sesso, Howard D.
Sigurdson, Alice J.
Wactawski-Wende, Jean
Zeleniuch-Jacquotte, Anne
Campbell, Peter T.
McGlynn, Katherine A.
TI NSAID Use and Risk of Hepatocellular Carcinoma and Intrahepatic
Cholangiocarcinoma: The Liver Cancer Pooling Project
SO CANCER PREVENTION RESEARCH
LA English
DT Article
ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; COLORECTAL-CANCER; UNITED-STATES;
CELL-GROWTH; ASPIRIN; CYCLOOXYGENASE-2; INHIBITORS; PREVENTION;
APOPTOSIS; SURVIVAL
AB Chronic inflammation plays a pivotal role in the pathogenesis of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC), the two most common types of liver cancer. A number of prior experimental studies have suggested that nonsteroidal antiinflammatory drugs (NSAIDs), including aspirin and ibuprofen, may potentially protect against liver cancer. However, no observational study has examined the associationbetween aspirin duration and dose or other over-the-counter non-aspirin NSAIDs, such as ibuprofen, and liver cancer incidence. Furthermore, the association between NSAID use and risk of ICC is unclear. As part of the Liver Cancer Pooling Project, we harmonized data on 1,084,133 individuals (HCC = 679, ICC = 225) from 10 U.S.-based prospective cohort studies. Cox proportional hazards regression models were used to evaluate multivariable-adjusted HRs and 95% confidence intervals (CI). Current aspirin use, versus nonuse, was inversely associated with HCC (HR, 0.68; 95% CI, 0.57-0.81), which persisted when restricted to individuals not using non-aspirin NSAIDs and in a 5-and 10-year lag analysis. The association between aspirin use and HCC risk was stronger for users who reported daily use, longer duration use, and lower dosage. Ibuprofen use was not associated with HCC risk. Aspirin usewas associated with a reduced ICC risk in men (HR, 0.64; 95% CI, 0.42-0.98) but not women (HR, 1.34; 95% CI, 0.89-2.01; P-interaction = 0.01). The observed inverse association between aspirin use and liver cancer in our study, together with previous data, suggests the merit of future intervention studies of aspirin and other agents that affect chronic inflammatory pathways for HCC and possibly ICC. (C) 2015 AACR.
C1 [Petrick, Jessica L.; Sahasrabuddhe, Vikrant V.; Alavanja, Michael C.; Beane-Freeman, Laura E.; Chen, Jie; Freedman, Neal D.; Graubard, Barry I.; Koshiol, Jill; Linet, Martha S.; Purdue, Mark P.; Schairer, Catherine; Sigurdson, Alice J.; McGlynn, Katherine A.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Sahasrabuddhe, Vikrant V.] NCI, Canc Prevent Div, Bethesda, MD 20892 USA.
[Sahasrabuddhe, Vikrant V.] Vanderbilt Univ, Sch Med, Dept Med, Nashville, TN 37212 USA.
[Sahasrabuddhe, Vikrant V.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA.
[Chan, Andrew T.; Chong, Dawn Q.; King, Lindsay Y.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA.
[Chan, Andrew T.; Chong, Dawn Q.; Fuchs, Charles S.; King, Lindsay Y.] Harvard Univ, Sch Med, Boston, MA USA.
[Buring, Julie E.; Giovannucci, Edward; Lee, I-Min; Sesso, Howard D.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Chong, Dawn Q.] Natl Canc Ctr Singapore, Div Med Oncol, Singapore, Singapore.
[Fuchs, Charles S.] Dana Farber Canc Inst, Dept Med, Boston, MA 02115 USA.
[Michael Gaziano, John] VA Boston Healthcare Syst, Brockton, MA USA.
[Hollenbeck, Albert R.] AARP, Washington, DC USA.
[Hou, Lifang] Northwestern Univ, Dept Prevent Med, Chicago, IL 60611 USA.
[Jacobs, Eric J.; Campbell, Peter T.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA.
[Palmer, Julie R.; Rosenberg, Lynn] Boston Univ, Slone Epidemiol Ctr, Boston, MA 02215 USA.
[Wactawski-Wende, Jean] SUNY Buffalo, Dept Epidemiol & Environm Hlth, Buffalo, NY 14260 USA.
[Zeleniuch-Jacquotte, Anne] NYU, Sch Med, Dept Populat Hlth, New York, NY USA.
RP Petrick, JL (reprint author), NCI, 9609 Med Ctr Dr,7E-232, Bethesda, MD 20892 USA.
EM jessica.petrick@nih.gov
RI Purdue, Mark/C-9228-2016; Beane Freeman, Laura/C-4468-2015;
OI Purdue, Mark/0000-0003-1177-3108; Beane Freeman,
Laura/0000-0003-1294-4124; Zeleniuch-Jacquotte, Anne/0000-0001-9350-1303
FU NIH Intramural Research Program, National Cancer Institute; National
Cancer Institute [CA047988, HL043851, HL080467, HL099355, DK098311,
CA186107, CA87969, CA167552]
FX The study was supported by NIH Intramural Research Program, National
Cancer Institute (J.L. Petrick, V.V. Sahasrabuddhe, M.C. Alavanja, L.
Beane-Freeman, J. Chen, N.D. Freedman, B.I. Graubard, J. Koshiol, M.S.
Linet, C. Schairer, A.J. Sigurdson, K.A. McGlynn). National Cancer
Institute Grants CA047988 (I. Lee, J.E. Buring), HL043851 (I. Lee, J.E.
Buring), HL080467 (I. Lee, J.E. Buring), HL099355 (I. Lee, J. E.
Buring), DK098311 (A.T. Chan), CA186107 (A.T. Chan), CA87969 (A.T.
Chan), and CA167552 (A.T. Chan).
NR 46
TC 1
Z9 1
U1 1
U2 7
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1940-6207
EI 1940-6215
J9 CANCER PREV RES
JI Cancer Prev. Res.
PD DEC
PY 2015
VL 8
IS 12
BP 1156
EP 1162
DI 10.1158/1940-6207.CAPR-15-0126
PG 7
WC Oncology
SC Oncology
GA DB5BS
UT WOS:000368528700004
PM 26391917
ER
PT J
AU Pretzel, SM
Andrews, TS
Broski, K
Childs, JC
Gren, LH
Ogden, SL
Mabie, J
Thomas, B
Rozjabek, HM
Marcus, PM
AF Pretzel, Shannon M.
Andrews, Tara S.
Broski, Karen
Childs, Jeffery C.
Gren, Lisa H.
Ogden, Sheryl L.
Mabie, Jerome
Thomas, Brett
Rozjabek, Heather M.
Marcus, Pamela M.
TI Participants' Views of Retention Materials Used in the PLCO Cancer
Screening Trial
SO CLINICAL MEDICINE & RESEARCH
LA English
DT Article
DE Randomized controlled trial as subject; Mass screening; Patient
compliance; Cancer; USA; Internet usage
ID MORTALITY; PROSTATE; LUNG
AB Objective: To obtain information from participants in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial regarding their perception of the retention materials employed by the screening centers. Also, to determine the viability of using email or the internet as a data collection tool with an older population.
Design: Three of ten PLCO screening centers queried participants towards the end of the study (2010) as to their opinions of the various retention materials and whether they would have been willing to use electronic communication for study activities, had the option been available. Setting: The questionnaires were administered by mail, and responses were returned to the originating screening center.
Participants: The participants in this study consisted of all the active participants at three PLCO screening centers: the University of Colorado Anschutz Medical Campus, the University of Utah, and Henry Ford Health System.
Methods: A short, self-administered questionnaire was mailed to all active participants at three PLCO centers (n= 41,482). This was a one-time mailing with no follow-up, as the responses were designed to be anonymous in order to obtain the most honest responses. Results: The response rate was 62%. Of respondents, 97% reported their PLCO experience was good or excellent. Nearly 50% of respondents indicated that receipt of an annual newsletter made them more likely to participate; newsletter features they reported as most important were those that conveyed information on cancer, study findings, and how their data were being used.
Results did not support study coordinators' suppositions that receipt of a token gift or birthday card by participants was important for retention. Fewer than 30% of respondents indicated that they would have been unwilling to use a secure website to complete study forms.
Conclusion: These data indicate the importance of querying participants rather than relying on impressions of study staff, and also indicate that the internet will be a viable means of data collection in future prevention studies that include older Americans.
C1 [Pretzel, Shannon M.; Ogden, Sheryl L.] Univ Colorado, Ctr Canc, Anschutz Med Campus,13001 E 17th Pl,Mail Stop C31, Aurora, CO 80045 USA.
[Andrews, Tara S.; Broski, Karen] Henry Ford Hlth Syst, Dept Publ Hlth Sci, Detroit, MI USA.
[Childs, Jeffery C.] Univ Utah, Div Oncol, Salt Lake City, UT USA.
[Gren, Lisa H.] Univ Utah, Dept Family & Prevent Med, Salt Lake City, UT USA.
[Mabie, Jerome; Thomas, Brett] Informat Management Syst, Rockville, MD USA.
[Rozjabek, Heather M.; Marcus, Pamela M.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Rozjabek, Heather M.] Drexel Univ, Sch Publ Hlth, Philadelphia, PA 19104 USA.
RP Pretzel, SM (reprint author), Univ Colorado, Anschutz Med Campus,13001 E 17th Pl,Mail Stop C31, Aurora, CO 80045 USA.
EM Shannon.pretzel@ucdenver.edu
OI Broski, Karen/0000-0003-1503-8768
FU NCI NIH HHS [N01-CN-25524, N01 CN25514, N01-CN-25512, N01 CN25524, N01
CN25512, N01-CN-25514, N02-CN-35001-45, N01 CN25476, N01-CN-25476,
N02-CN-55023-76]
NR 9
TC 0
Z9 0
U1 0
U2 0
PU MARSHFIELD CLINIC
PI MARSHFIELD
PA 1000 N OAK AVE, MAILSTOP ML7, MARSHFIELD, WI 54449 USA
SN 1539-4182
EI 1554-6179
J9 CLIN MED RES
JI Clin. Med. Res.
PD DEC 1
PY 2015
VL 13
IS 3-4
BP 139
EP 146
DI 10.3121/cmr.2015.1274
PG 8
WC Medicine, General & Internal
SC General & Internal Medicine
GA DB5UW
UT WOS:000368580100004
PM 26387707
ER
PT J
AU Mayer-Barber, KD
Barber, DL
AF Mayer-Barber, Katrin D.
Barber, Daniel L.
TI Innate and Adaptive Cellular Immune Responses to Mycobacterium
tuberculosis Infection
SO COLD SPRING HARBOR PERSPECTIVES IN MEDICINE
LA English
DT Article
ID CD4(+) T-CELLS; IMMUNODEFICIENCY-VIRUS-INFECTION; RECONSTITUTION
INFLAMMATORY SYNDROME; NITRIC-OXIDE SYNTHASE;
PNEUMOCYSTIS-CARINII-PNEUMONIA; LUNG DENDRITIC CELLS; W-BEIJING STRAINS;
IN-VIVO DEPLETION; PULMONARY TUBERCULOSIS; INTERFERON-GAMMA
AB Host resistance to Mycobacterium tuberculosis (Mtb) infection requires the coordinated efforts of innate and adaptive immune cells. Diverse pulmonary myeloid cell populations respond to Mtb with unique contributions to both host-protective and potentially detrimental inflammation. Although multiple cell types of the adaptive immune system respond to Mtb infection, CD4 T cells are the principal antigen-specific cells responsible for containment of Mtb infection, but they can also be major contributors to disease during Mtb infection in several different settings. Here, we will discuss the role of different myeloid populations as well as the dual nature of CD4 T cells in Mtb infection with a primary focus on data generated using in vivo cellular immunological studies in experimental animal models and in humans when available.
C1 [Mayer-Barber, Katrin D.] NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
[Barber, Daniel L.] NIAID, Lymphocyte Biol Unit T, Parasit Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
RP Mayer-Barber, KD (reprint author), NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM barberd@niaid.nih.gov
NR 169
TC 0
Z9 0
U1 3
U2 5
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 DEC
PY 2015
VL 5
IS 12
AR a018424
DI 10.1101/cshperspect.a018424
PG 19
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA DB6CA
UT WOS:000368599500008
ER
PT J
AU Garfinkel, BP
Arad, S
Le, PT
Bustin, M
Rosen, CJ
Gabet, Y
Orly, J
AF Garfinkel, Benjamin P.
Arad, Shiri
Le, Phuong T.
Bustin, Michael
Rosen, Clifford J.
Gabet, Yankel
Orly, Joseph
TI Proportionate Dwarfism in Mice Lacking Heterochromatin Protein 1 Binding
Protein 3 (HP1BP3) Is Associated With Alterations in the Endocrine IGF-1
Pathway
SO ENDOCRINOLOGY
LA English
DT Article
ID GROWTH-FACTOR-I; BONE-MINERAL DENSITY; TRANSGENIC MICE;
POSTNATAL-GROWTH; HORMONE RECEPTOR; TARGETED DISRUPTION;
GENETIC-EVIDENCE; SKELETAL GROWTH; SERUM IGF-1; AGING MEN
AB Heterochromatin protein 1 binding protein 3 (HP1BP3) is a recently described histone H1-related protein with roles in chromatin structure and transcriptional regulation. To explore the potential physiological role of HP1BP3, we have previously described an Hp1bp3(-/-) mouse model with reduced postnatal viability and growth. We now find that these mice are proportionate dwarfs, with reduction in body weight, body length, and organ weight. In addition to their small size, microcomputed tomography analysis showed that Hp1bp3(-/-) mice present a dramatic impairment of their bone development and structure. By 3 weeks of age, mice of both sexes have severely impaired cortical and trabecular bone, and these defects persist into adulthood and beyond. Primary cultures of both osteoblasts and osteoclasts from Hp1bp3(-/-) bone marrow and splenocytes, respectively, showed normal differentiation and function, strongly suggesting that the impaired bone accrual is due to noncell autonomous systemic cues in vivo. One major endocrine pathway regulating both body growth and bone acquisition is the IGF regulatory system, composed of IGF-1, the IGF receptors, and the IGF-binding proteins (IGFBPs). At 3 weeks of age, Hp1bp3(-/-) mice exhibited a 60% reduction in circulating IGF-1 and a 4-fold increase in the levels of IGFBP-1 and IGFBP-2. These alterations were reflected in similar changes in the hepatic transcripts of the Igf1, Igfbp1, and Igfbp2 genes. Collectively, these results suggest that HP1BP3 plays a key role in normal growth and bone development by regulating transcription of endocrine IGF-1 components.
C1 [Garfinkel, Benjamin P.; Arad, Shiri; Orly, Joseph] Hebrew Univ Jerusalem, Alexander Silberman Inst Life Sci, Dept Biol Chem, IL-91904 Jerusalem, Israel.
[Le, Phuong T.; Rosen, Clifford J.] Maine Med Ctr Res Inst, Ctr Clin & Translat Res, Scarborough, ME 04074 USA.
[Bustin, Michael] NCI, Prot Sect, Lab Metab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
[Gabet, Yankel] Tel Aviv Univ, Sackler Fac Med, Dept Anat & Anthropol, IL-64239 Tel Aviv, Israel.
RP Orly, J (reprint author), Hebrew Univ Jerusalem, Alexander Silberman Inst Life Sci, Dept Biol Chem, IL-91904 Jerusalem, Israel.
EM benny.garfinkel@mail.huji.ac.il; orly@vms.huji.ac.il
RI Bustin, Michael/G-6155-2015
FU United States-Israel Binational Science Foundation Grants [2009326,
2013194]
FX This work was supported by The United States-Israel Binational Science
Foundation Grants 2009326 (to J.O. and M.B.) and 2013194 (to C.J.R. and
J.O.).
NR 57
TC 3
Z9 3
U1 0
U2 5
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 DEC
PY 2015
VL 156
IS 12
BP 4558
EP 4570
DI 10.1210/en.2015-1668
PG 13
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA DB3KT
UT WOS:000368410900017
PM 26402843
ER
PT J
AU Varki, A
Cummings, RD
Aebi, M
Packer, NH
Seeberger, PH
Esko, JD
Stanley, P
Hart, G
Darvill, A
Kinoshita, T
Prestegard, JJ
Schnaar, RL
Freeze, HH
Marth, JD
Bertozzi, CR
Etzler, ME
Frank, M
Vliegenthart, JFG
Lutteke, T
Perez, S
Bolton, E
Rudd, P
Paulson, J
Kanehisa, M
Toukach, P
Aoki-Kinoshita, KF
Dell, A
Narimatsu, H
York, W
Taniguchi, N
Kornfeld, S
AF Varki, Ajit
Cummings, Richard D.
Aebi, Markus
Packer, Nicole H.
Seeberger, Peter H.
Esko, Jeffrey D.
Stanley, Pamela
Hart, Gerald
Darvill, Alan
Kinoshita, Taroh
Prestegard, James J.
Schnaar, Ronald L.
Freeze, Hudson H.
Marth, Jamey D.
Bertozzi, Carolyn R.
Etzler, Marilynn E.
Frank, Martin
Vliegenthart, Johannes F. G.
Luetteke, Thomas
Perez, Serge
Bolton, Evan
Rudd, Pauline
Paulson, James
Kanehisa, Minoru
Toukach, Philip
Aoki-Kinoshita, Kiyoko F.
Dell, Anne
Narimatsu, Hisashi
York, William
Taniguchi, Naoyuki
Kornfeld, Stuart
TI Symbol Nomenclature for Graphical Representations of Glycans
SO GLYCOBIOLOGY
LA English
DT Editorial Material
C1 [Varki, Ajit; Esko, Jeffrey D.] Univ Calif San Diego, La Jolla, CA 92093 USA.
[Cummings, Richard D.] Consortium Funct Glycom, London, England.
[Cummings, Richard D.] Harvard Univ, Sch Med, Boston, MA USA.
[Aebi, Markus] ETH, Zurich, Switzerland.
[Packer, Nicole H.] Macquarie Univ, Sydney, NSW 2109, Australia.
[Seeberger, Peter H.] Max Planck Inst, Potsdam, Germany.
[Stanley, Pamela] Albert Einstein Coll Med, New York, NY USA.
[Hart, Gerald; Schnaar, Ronald L.] Johns Hopkins Univ, Baltimore, MD USA.
[Darvill, Alan; Prestegard, James J.; York, William] Univ Georgia, Athens, GA 30602 USA.
[Kinoshita, Taroh] Osaka Univ, Osaka, Japan.
[Freeze, Hudson H.] Sanford Burnham Prebys Med Discovery Inst, La Jolla, CA USA.
[Marth, Jamey D.] Univ Calif Santa Barbara, Santa Barbara, CA 93106 USA.
[Bertozzi, Carolyn R.] Stanford Univ, Stanford, CA 94305 USA.
[Etzler, Marilynn E.] Univ Calif Davis, Davis, CA 95616 USA.
[Frank, Martin; Vliegenthart, Johannes F. G.; Luetteke, Thomas] IUPAC Carbohydrate Nomenclature Comm, Gothenburg, Sweden.
[Frank, Martin] Biognos AB, Gothenburg, Sweden.
[Vliegenthart, Johannes F. G.] Univ Utrecht, Utrecht, Netherlands.
[Luetteke, Thomas] MonosaccharideDB, Giessen, Germany.
[Luetteke, Thomas] Univ Giessen, Giessen, Germany.
[Perez, Serge] Glycopedia, St Martin Dheres, France.
[Perez, Serge] Univ Grenoble Alpes, CNRS, St Martin Dheres, France.
[Bolton, Evan] Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA.
[Bolton, Evan] Natl Lib Med, Bethesda, MD USA.
[Rudd, Pauline] Oxford Glycobiol Inst, Dublin, Ireland.
[Rudd, Pauline] Natl Inst Bioproc Res & Training, Dublin, Ireland.
[Paulson, James] Consortium Funct Glyc, La Jolla, CA USA.
[Paulson, James] Scripps Res Inst, La Jolla, CA 92037 USA.
[Kanehisa, Minoru] KEGG Database, Kyoto, Japan.
[Kanehisa, Minoru] Kyoto Univ, Kyoto, Japan.
[Toukach, Philip] Carbohydrate Struct Database CSDB, Moscow, Russia.
[Toukach, Philip] Zelinsky Inst Organ Chem, Moscow, Russia.
[Aoki-Kinoshita, Kiyoko F.] GlyTouCan Database, Tokyo, Japan.
[Aoki-Kinoshita, Kiyoko F.] Soka Univ, Tokyo, Japan.
[Dell, Anne] Univ London Imperial Coll Sci Technol & Med, London, England.
[Narimatsu, Hisashi] Natl Inst Adv Ind Sci & Technol, Tsukuba, Ibaraki, Japan.
[Taniguchi, Naoyuki] RIKEN, Saitama, Japan.
[Kornfeld, Stuart] Washington Univ, Sch Med, St Louis, MO USA.
RP Varki, A (reprint author), Univ Calif San Diego, La Jolla, CA 92093 USA.
RI Aoki-Kinoshita, Kiyoko/I-2696-2016; Schnaar, Ronald/S-8967-2016;
OI Aoki-Kinoshita, Kiyoko/0000-0002-6662-8015; Schnaar,
Ronald/0000-0002-7701-5484; Freeze, Hudson/0000-0001-6316-0501; Lutteke,
Thomas/0000-0002-7140-9933; Toukach, Philip/0000-0001-9887-8919
FU NHLBI NIH HHS [P01 HL107151, R01 HL125352]; NIDDK NIH HHS [R01
DK099551]; NIGMS NIH HHS [R01 GM105399]
NR 8
TC 36
Z9 36
U1 8
U2 28
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0959-6658
EI 1460-2423
J9 GLYCOBIOLOGY
JI Glycobiology
PD DEC
PY 2015
VL 25
IS 12
BP 1323
EP 1324
DI 10.1093/glycob/cwv091
PG 2
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA DB3WL
UT WOS:000368443700002
PM 26543186
ER
PT J
AU Kun-Rodrigues, C
Ganos, C
Guerreiro, R
Schneider, SA
Schulte, C
Lesage, S
Darwent, L
Holmans, P
Singleton, A
Bhatia, K
Bras, J
AF Kun-Rodrigues, Celia
Ganos, Christos
Guerreiro, Rita
Schneider, Susanne A.
Schulte, Claudia
Lesage, Suzanne
Darwent, Lee
Holmans, Peter
Singleton, Andrew
Bhatia, Kailash
Bras, Jose
CA Int Parkinson's Dis Genomics
TI A systematic screening to identify de novo mutations causing sporadic
early-onset Parkinson's disease
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID AMYOTROPHIC-LATERAL-SCLEROSIS; AUTISM SPECTRUM DISORDERS; SYNUCLEIN GENE
DUPLICATION; PTEN TUMOR-SUPPRESSOR; PRESENILIN-1 GENE; VAPB; GERMLINE;
NEURONS; ALS; DELETION
AB Despite the many advances in our understanding of the genetic basis of Mendelian forms of Parkinson's disease (PD), a large number of early-onset cases still remain to be explained. Many of these cases, present with a form of disease that is identical to that underlined by genetic causes, but do not have mutations in any of the currently known disease-causing genes. Here, we hypothesized that de novo mutations may account for a proportion of these early-onset, sporadic cases. We performed exome sequencing in full parent-child trios where the proband presents with typical PD to unequivocally identify de novo mutations. This approach allows us to test all genes in the genome in an unbiased manner. We have identified and confirmed 20 coding de novo mutations in 21 trios. We have used publicly available population genetic data to compare variant frequencies and our independent in-house dataset of exome sequencing in PD (with over 1200 cases) to identify additional variants in the same genes. Of the genes identified to carry de novo mutations, PTEN, VAPB and ASNA1 are supported by various sources of data to be involved in PD. We show that these genes are reported to be within a protein-protein interaction network with PD genes and that they contain additional rare, case-specific, mutations in our independent cohort of PD cases. Our results support the involvement of these three genes in PD and suggest that testing for de novo mutations in sporadic disease may aid in the identification of novel disease-causing genes.
C1 [Kun-Rodrigues, Celia; Guerreiro, Rita; Darwent, Lee; Bras, Jose] UCL Inst Neurol, Dept Mol Neurosci, London WC1N 3AR, England.
[Ganos, Christos] Univ Med Ctr Hamburg Eppendorf UKE, Dept Neurol, D-20246 Hamburg, Germany.
[Ganos, Christos; Bhatia, Kailash] UCL, UCL Inst Neurol, Sobell Dept Motor Neurosci & Movement Disorders, London WC1N 3BG, England.
[Schneider, Susanne A.] Univ Hosp Schleswig Holstein, Dept Neurol, D-24105 Kiel, Germany.
[Schulte, Claudia] German Ctr Neurodegenerat Dis, Tubingen, Germany.
[Schulte, Claudia] Univ Tubingen, Hertie Inst Clin Brain Res, Dept Neurodegenerat Dis, D-72076 Tubingen, Germany.
[Lesage, Suzanne] Hop La Pitie Salpetriere, Brain & Spinal Cord Inst ICM, INSERM, U M27, F-75013 Paris, France.
[Holmans, Peter] Cardiff Univ, Inst Psychol Med & Clin Neurosci, Med Res Council, Ctr Neuropsychiat Genet & Gen, Cardiff CF24 4HQ, S Glam, Wales.
[Singleton, Andrew] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
RP Bras, J (reprint author), UCL, Inst Neurol, Dept Mol Neurosci, DRC, 8-11 Queen Sq,Box 16, London WC1N 3AR, England.
EM j.bras@ucl.ac.uk
RI Singleton, Andrew/C-3010-2009;
OI Bras, Jose/0000-0001-8186-0333; Holmans, Peter/0000-0003-0870-9412
FU Wellcome Trust; Medical Research Council
FX Funding to pay the Open Access publication charges for this article was
provided by the Wellcome Trust and the Medical Research Council.
NR 64
TC 3
Z9 3
U1 2
U2 11
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 DEC 1
PY 2015
VL 24
IS 23
BP 6711
EP 6720
DI 10.1093/hmg/ddv376
PG 10
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA DB2WP
UT WOS:000368371600013
PM 26362251
ER
PT J
AU Gharib, SA
Loth, DW
Artigas, MS
Birkland, TP
Wilk, JB
Wain, LV
Brody, JA
Obeidat, M
Hancock, DB
Tang, WB
Rawal, R
Boezen, HM
Imboden, M
Huffman, JE
Lahousse, L
Alves, AC
Manichaikul, A
Hui, J
Morrison, AC
Ramasamy, A
Smith, AV
Gudnason, V
Surakka, I
Vitart, V
Evans, DM
Strachan, DP
Deary, IJ
Hofman, A
Glaser, S
Wilson, JF
North, KE
Zhao, JH
Heckbert, SR
Jarvis, DL
Probst-Hensch, N
Schulz, H
Barr, RG
Jarvelin, MR
O'Connor, GT
Kahonen, M
Cassano, PA
Hysi, PG
Dupuis, J
Hayward, C
Psaty, BM
Hall, IP
Parks, WC
Tobin, MD
London, SJ
AF Gharib, Sina A.
Loth, Daan W.
Artigas, Maria Soler
Birkland, Timothy P.
Wilk, Jemma B.
Wain, Louise V.
Brody, Jennifer A.
Obeidat, Ma'en
Hancock, Dana B.
Tang, Wenbo
Rawal, Rajesh
Boezen, H. Marike
Imboden, Medea
Huffman, Jennifer E.
Lahousse, Lies
Alves, Alexessander C.
Manichaikul, Ani
Hui, Jennie
Morrison, Alanna C.
Ramasamy, Adaikalavan
Smith, Albert Vernon
Gudnason, Vilmundur
Surakka, Ida
Vitart, Veronique
Evans, David M.
Strachan, David P.
Deary, Ian J.
Hofman, Albert
Glaeser, Sven
Wilson, James F.
North, Kari E.
Zhao, Jing Hua
Heckbert, Susan R.
Jarvis, Deborah L.
Probst-Hensch, Nicole
Schulz, Holger
Barr, R. Graham
Jarvelin, Marjo-Riitta
O'Connor, George T.
Kahonen, Mika
Cassano, Patricia A.
Hysi, Pirro G.
Dupuis, Josee
Hayward, Caroline
Psaty, Bruce M.
Hall, Ian P.
Parks, William C.
Tobin, Martin D.
London, Stephanie J.
CA CHARGE Consortium
SpiroMeta Consortium
TI Integrative pathway genomics of lung function and airflow obstruction
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID SET ENRICHMENT ANALYSIS; WIDE ASSOCIATION; PULMONARY-DISEASE; MATRIX
METALLOPROTEINASES; GENOMEWIDE ASSOCIATION; EXPRESSION; RISK;
IDENTIFICATION; INFLAMMATION; METAANALYSIS
AB Chronic respiratory disorders are important contributors to the global burden of disease. Genome-wide association studies (GWASs) of lung function measures have identified several trait-associated loci, but explain only a modest portion of the phenotypic variability. We postulated that integrating pathway-based methods with GWASs of pulmonary function and airflow obstruction would identify a broader repertoire of genes and processes influencing these traits. We performed two independent GWASs of lung function and applied gene set enrichment analysis to one of the studies and validated the results using the second GWAS. We identified 131 significantly enriched gene sets associated with lung function and clustered them into larger biological modules involved in diverse processes including development, immunity, cell signaling, proliferation and arachidonic acid. We found that enrichment of gene sets was not driven by GWAS-significant variants or loci, but instead by those with less stringent association P-values. Next, we applied pathway enrichment analysis to a meta-analyzed GWAS of airflow obstruction. We identified several biologic modules that functionally overlapped with those associated with pulmonary function. However, differences were also noted, including enrichment of extracellular matrix (ECM) processes specifically in the airflow obstruction study. Network analysis of the ECM module implicated a candidate gene, matrix metalloproteinase 10 (MMP10), as a putative disease target. We used a knockout mouse model to functionally validate MMP10' s role in influencing lung's susceptibility to cigarette smoke-induced emphysema. By integrating pathway analysis with population-based genomics, we unraveled biologic processes underlying pulmonary function traits and identified a candidate gene for obstructive lung disease.
C1 [Gharib, Sina A.; Birkland, Timothy P.] Univ Washington, Ctr Lung Biol, Computat Med Core, Seattle, WA 98195 USA.
[Gharib, Sina A.; Psaty, Bruce M.] Univ Washington, Dept Med, Seattle, WA USA.
[Brody, Jennifer A.; Heckbert, Susan R.; Psaty, Bruce M.] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.
[Heckbert, Susan R.; Psaty, Bruce M.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA.
[Loth, Daan W.; Lahousse, Lies; Hofman, Albert] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.
[Artigas, Maria Soler; Wain, Louise V.; Tobin, Martin D.] Univ Leicester, Dept Hlth Sci, Genet Epidemiol Grp, Leicester, Leics, England.
[Artigas, Maria Soler; Wain, Louise V.; Tobin, Martin D.] Glenfield Hosp, Leicester Resp Biomed Res Unit, NIHR, Leicester, Leics, England.
[Wilk, Jemma B.] Pfizer Global Res & Dev, Human Genet & Computat Biomed, Cambridge, MA USA.
[Obeidat, Ma'en] Univ British Columbia, Ctr Heart Lung Innovat, Vancouver, BC V5Z 1M9, Canada.
[Hancock, Dana B.] Res Triangle Inst RTI Int, Behav Hlth & Criminal Justice Div, Behav & Urban Hlth Program, Res Triangle Pk, NC USA.
[Tang, Wenbo; Cassano, Patricia A.] Cornell Univ, Div Nutr Sci, Ithaca, NY 14853 USA.
[Rawal, Rajesh] German Res Ctr Environm Hlth, Inst Genet Epidemiol, Helmholtz Zentrum Munchen, Neuherberg, Germany.
[Schulz, Holger] German Res Ctr Environm Hlth, Inst Epidemiol 1, Helmholtz Zentrum Munchen, Neuherberg, Germany.
[Boezen, H. Marike] Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Groningen, Netherlands.
[Boezen, H. Marike] Univ Groningen, Univ Med Ctr Groningen, GRIAC Res Inst, Groningen, Netherlands.
[Imboden, Medea; Probst-Hensch, Nicole] Swiss Trop & Publ Hlth Inst, Basel, Switzerland.
[Imboden, Medea; Probst-Hensch, Nicole] Univ Basel, Basel, Switzerland.
[Huffman, Jennifer E.; Vitart, Veronique; Hayward, Caroline] Univ Edinburgh, MRC IGMM, MRC Human Genet Unit, Edinburgh, Midlothian, Scotland.
[Deary, Ian J.] Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh, Midlothian, Scotland.
[Wilson, James F.] Univ Edinburgh, Usher Inst Populat Hlth Sci & Informat, Edinburgh, Midlothian, Scotland.
[Lahousse, Lies] Ghent Univ Hosp, Dept Resp Med, Ghent, Belgium.
[Alves, Alexessander C.] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, London, England.
[Jarvis, Deborah L.] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, Resp Epidemiol & Publ Hlth Grp, London, England.
[Jarvelin, Marjo-Riitta] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Ctr Environm & Hlth, Dept Epidemiol & Biostat,MRC Hlth Protect Agcy HP, London, England.
[Manichaikul, Ani] Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA USA.
[Manichaikul, Ani] Univ Virginia, Dept Publ Hlth Sci, Div Biostat & Epidemiol, Charlottesville, VA USA.
[Hui, Jennie] PathWest Lab Med WA, Nedlands, WA, Australia.
[Hui, Jennie] Univ Western Australia, Sch Populat Hlth, Sch Pathol & Lab Med, Nedlands, WA 6009, Australia.
[Morrison, Alanna C.] Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Human Genet Ctr, Houston, TX 77030 USA.
[Ramasamy, Adaikalavan] Kings Coll London, Dept Med & Mol Genet, London WC2R 2LS, England.
[Hysi, Pirro G.] Kings Coll London, Dept Twins Res & Genet Epidemiol, London WC2R 2LS, England.
[Smith, Albert Vernon; Gudnason, Vilmundur] Iceland Heart Assoc, Kopavogur, Iceland.
[Smith, Albert Vernon; Gudnason, Vilmundur] Univ Iceland, Reykjavik, Iceland.
[Surakka, Ida] Natl Inst Hlth & Welf THL, Dept Chron Dis Prevent, Publ Hlth Genom Unit, Helsinki, Finland.
[Evans, David M.] Univ Queensland, Diamantina Inst, Translat Res Inst, Woolloongabba, Qld 4102, Australia.
[Evans, David M.] MRC Integrat Epidemiol Unit, Bristol BS8 2BN, Avon, England.
[Strachan, David P.] Univ London, Populat Hlth Res Inst, London, England.
[Hofman, Albert] NGI, Consortium Healthy Aging NCHA, Rotterdam, Netherlands.
[Glaeser, Sven] Univ Hosp Greifswald, Dept Internal Med Pneumol Cardiol Intens Care &, Greifswald, Germany.
[Zhao, Jing Hua] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA.
[Zhao, Jing Hua] Addenbrookes Hosp, Inst Metab Sci, MRC Epidemiol Unit, Cambridge, England.
[Heckbert, Susan R.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA.
[Barr, R. Graham] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY USA.
[Jarvelin, Marjo-Riitta] Univ Oulu, Inst Hlth Sci, Oulu, Finland.
[Jarvelin, Marjo-Riitta] Univ Oulu, Bioctr Oulu, Oulu, Finland.
[Jarvelin, Marjo-Riitta] Oulu Univ Hosp, Unit Primary Care, Oulu, Finland.
[Jarvelin, Marjo-Riitta] Natl Inst Hlth & Welfare, Dept Children & Young People & Families, Oulu, Finland.
[O'Connor, George T.] Boston Univ, Sch Med, Pulmonary Ctr, Boston, MA 02118 USA.
[O'Connor, George T.; Dupuis, Josee] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Kahonen, Mika] Univ Tampere, Dept Clin Physiol, FIN-33101 Tampere, Finland.
[Kahonen, Mika] Tampere Univ Hosp, Tampere, Finland.
[Cassano, Patricia A.] Weill Cornell Med Coll, Div Biostat & Epidemiol, Dept Healthcare Policy & Res, New York, NY USA.
[Dupuis, Josee] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Hall, Ian P.] Univ Nottingham Hosp, Div Resp Med, Nottingham NG7 2UH, England.
[Parks, William C.] Cedars Sinai Med Ctr, Dept Med, Los Angeles, CA 90048 USA.
[London, Stephanie J.] NIEHS, Epidemiol Branch, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
RP Gharib, SA (reprint author), 850 Republ St,POB 358052, Seattle, WA 98109 USA.
EM sagharib@u.washington.edu
RI Soler Artigas, Maria/L-6529-2013; Smith, Albert Vernon/K-5150-2015;
OI Soler Artigas, Maria/0000-0002-3213-1107; Smith, Albert
Vernon/0000-0003-1942-5845; Manichaikul, Ani/0000-0002-5998-795X; Evans,
David/0000-0003-0663-4621; Lahousse, Lies/0000-0002-3494-4363; London,
Stephanie/0000-0003-4911-5290; Wain, Louise/0000-0003-4951-1867
FU Biotechnology and Biological Sciences Research Council [BB/F019394/1];
Chief Scientist Office [CZB/4/505, ETM/55]; MRC [G0902313, G1000861,
G1001799, MC_PC_12010, MC_PC_U127561128, MC_UU_12013/4, MR/K026992/1,
MR/N01104X/1]
NR 62
TC 3
Z9 3
U1 0
U2 8
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 DEC 1
PY 2015
VL 24
IS 23
BP 6836
EP 6848
DI 10.1093/hmg/ddv378
PG 13
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA DB2WP
UT WOS:000368371600022
PM 26395457
ER
PT J
AU Hagg, S
Ganna, A
Van der Laan, SW
Esko, T
Pers, TH
Locke, AE
Berndt, SI
Justice, AE
Kahali, B
Siemelink, MA
Pasterkamp, G
Strachan, DP
Speliotes, EK
North, KE
Loos, RJF
Hirschhorn, JN
Pawitan, Y
Ingelsson, E
AF Hagg, Sara
Ganna, Andrea
Van der Laan, Sander W.
Esko, Tonu
Pers, Tune H.
Locke, Adam E.
Berndt, Sonja I.
Justice, Anne E.
Kahali, Bratati
Siemelink, Marten A.
Pasterkamp, Gerard
Strachan, David P.
Speliotes, Elizabeth K.
North, Kari E.
Loos, Ruth J. F.
Hirschhorn, Joel N.
Pawitan, Yudi
Ingelsson, Erik
CA GIANT Consortium
TI Gene-based meta-analysis of genome-wide association studies implicates
new loci involved in obesity
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID ACTIN-INTERACTING PROTEIN; BODY-MASS INDEX; MITOCHONDRIAL TRNA(ILE);
MISSING HERITABILITY; DATABASE; VARIANTS; TISSUE; CELLS; KRAP; MICE
AB To date, genome-wide association studies (GWASs) have identified > 100 loci with single variants associated with body mass index (BMI). This approach may miss loci with high allelic heterogeneity; therefore, the aim of the present study was to use gene-based meta-analysis to identify regions with high allelic heterogeneity to discover additional obesity susceptibility loci. We included GWAS data from 123 865 individuals of European descent from 46 cohorts in Stage 1 and Metabochip data from additional 103 046 individuals from 43 cohorts in Stage 2, all within the Genetic Investigation of AN thropometric Traits (GIANT) consortium. Each cohort was tested for association between similar to 2.4million (Stage 1) or similar to 200 000 (Stage 2) imputed or genotyped single variants and BMI, and summary statistics were subsequently meta-analyzed in 17 941 genes. We used the 'VErsatile Gene-based Association Study' (VEGAS) approach to assign variants to genes and to calculate gene-based P-values based on simulations. The VEGAS method was applied to each cohort separately before a gene-based meta-analysis was performed. In Stage 1, two known (FTO and TMEM18) and six novel (PEX2, MTFR2, SSFA2, IARS2, CEP295 and TXNDC12) loci were associated with BMI (P < 2.8x10(-6) for 17 941 gene tests). We confirmed all loci, and six of them were gene-wide significant in Stage 2 alone. We provide biological support for the loci by pathway, expression and methylation analyses. Our results indicate that gene-based meta-analysis of GWAS provides a useful strategy to find loci of interest that were not identified in standard single-marker analyses due to high allelic heterogeneity.
C1 [Hagg, Sara; Pawitan, Yudi] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
[Hagg, Sara; Ingelsson, Erik] Uppsala Univ, Dept Med Sci, Mol Epidemiol & Sci Life Lab, SE-75141 Uppsala, Sweden.
[Ganna, Andrea] Broad Inst MIT & Harvard, Program Med & Populat Genet, Cambridge, MA USA.
[Ganna, Andrea] Massachusetts Gen Hosp, Dept Med, Analyt & Translat Genet Unit, Boston, MA 02114 USA.
[Ganna, Andrea] Harvard Univ, Sch Med, Boston, MA USA.
[Van der Laan, Sander W.; Siemelink, Marten A.; Pasterkamp, Gerard] Univ Med Ctr Utrecht, Div Heart & Lungs, Lab Expt Cardiol, NL-3584 CX Utrecht, Netherlands.
[Esko, Tonu; Pers, Tune H.; Hirschhorn, Joel N.] Boston Childrens Hosp, Div Endocrinol & Genet, Boston, MA 02115 USA.
[Esko, Tonu; Pers, Tune H.; Hirschhorn, Joel N.] Boston Childrens Hosp, Ctr Basic & Translat Obes Res, Boston, MA 02115 USA.
[Esko, Tonu; Pers, Tune H.; Hirschhorn, Joel N.] Broad Inst Massachusetts Inst Technol & Harvard U, Cambridge, MA 02142 USA.
[Esko, Tonu; Pers, Tune H.; Hirschhorn, Joel N.] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA.
[Esko, Tonu] Univ Tartu, Estonian Genome Ctr, EE-51010 Tartu, Estonia.
[Pers, Tune H.] Statens Serum Inst, Dept Epidemiol Res, DK-2300 Copenhagen, Denmark.
[Pers, Tune H.] Univ Copenhagen, Novo Nordisk Fdn Ctr Basic Metab Res, Copenhagen, Denmark.
[Locke, Adam E.] Univ Michigan, Ctr Stat Genet, Dept Biostat, Ann Arbor, MI 48109 USA.
[Kahali, Bratati; Speliotes, Elizabeth K.] Univ Michigan, Dept Internal Med, Div Gastroenterol, Ann Arbor, MI 48109 USA.
[Kahali, Bratati; Speliotes, Elizabeth K.] Univ Michigan, Dept Computat Med & Bioinformat, Ann Arbor, MI 48109 USA.
[Berndt, Sonja I.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Justice, Anne E.; North, Kari E.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27599 USA.
[North, Kari E.] Univ N Carolina, Carolina Ctr Genome Sci, Chapel Hill, NC 27599 USA.
[Pasterkamp, Gerard] UMC Utrecht, Lab Clin Chem & Hematol, Div Labs & Pharm, Utrecht, Netherlands.
[Strachan, David P.] Univ London, London SW17 0RE, England.
[Loos, Ruth J. F.] Univ Cambridge, Addenbrookes Hosp, MRC Epidemiol Unit, Inst Metab Sci, Cambridge CB2 0QQ, England.
[Loos, Ruth J. F.] Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA.
[Loos, Ruth J. F.] Univ Oxford, Genet Obes & Related Metab Traits Program, Oxford, England.
[Loos, Ruth J. F.] Univ Oxford, Mindich Child Hlth & Dev Inst, Oxford, England.
[Ingelsson, Erik] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.
[Ingelsson, Erik] Stanford Univ, Sch Med, Div Cardiovasc Med, Dept Med, Stanford, CA 94305 USA.
RP Ingelsson, E (reprint author), Uppsala Univ, Dept Med Sci, Mol Epidemiol & Sci Life Lab, SE-75141 Uppsala, Sweden.
EM erik.ingelsson@medsci.uu.se
OI Locke, Adam/0000-0001-6227-198X; Ganna, Andrea/0000-0002-8147-240X
FU Foundation for Geriatric Diseases, Karolinska Institutet
FX The study was supported by the Foundation for Geriatric Diseases,
Karolinska Institutet.
NR 43
TC 6
Z9 6
U1 2
U2 10
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 DEC 1
PY 2015
VL 24
IS 23
BP 6849
EP 6860
DI 10.1093/hmg/ddv379
PG 12
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA DB2WP
UT WOS:000368371600023
PM 26376864
ER
PT J
AU Baird, DD
Saldana, TM
Shore, DL
Hill, MC
Schectman, JM
AF Baird, D. D.
Saldana, T. M.
Shore, D. L.
Hill, M. C.
Schectman, J. M.
TI A single baseline ultrasound assessment of fibroid presence and size is
strongly predictive of future uterine procedure: 8-year follow-up of
randomly sampled premenopausal women aged 35-49 years
SO HUMAN REPRODUCTION
LA English
DT Article
DE uterine leiomyoma; ultrasonography; disease progression; hysterectomy;
heath disparity
ID ULIPRISTAL ACETATE; NATURAL-HISTORY; WHITE WOMEN; LEIOMYOMATA;
HYSTERECTOMY; GROWTH; EPIDEMIOLOGY; MANAGEMENT; DIAGNOSIS
AB STUDY QUESTION: How well can a single baseline ultrasound assessment of fibroid burden (presence or absence of fibroids and size of largest, if present) predict future probability of having a major uterine procedure?
SUMMARY ANSWER: During an 8-year follow-up period, the risk of having a major uterine procedure was 2% for those without fibroids and increased with fibroid size for those with fibroids, reaching >= 7% for those with fibroids >= 4 cm in diameter at baseline.
WHAT IS KNOWN ALREADY: Uterine fibroids are a leading indication for hysterectomy. However, when fibroids are found, there are few available data to help clinicians advise patients about disease progression.
STUDY DESIGN, SIZE, DURATION: Women who were 35-49 years old were randomly selected from the membership of a large urban health plan; 80% of those determined to be eligible were enrolled and screened with ultrasound for fibroids >= 0.5 cm in diameter. African-American and white premenopausal participants who responded to at least one follow-up interview (N = 964, 85% of those eligible) constituted the study cohort. During follow-up (5822 person-years), participants self-reported any major uterine procedure (67% hysterectomies). Life-table analyses and Cox regression (with censoring for menopause) were used to estimate the risk of having a uterine procedure for women with no fibroids, small (<2 cm in diameter), medium (2-3.9 cm), and large fibroids (>= 4 cm). Differences between African-American and white women, importance of a clinical diagnosis of fibroids prior to study enrollment, and the impact of submucosal fibroids on risk were investigated.
PARTICIPANTS/MATERIALS, SETTING, METHODS: There was a greater loss to follow-up for African-Americans than whites (19 versus 11%). For those with follow-up data, 64% had fibroids at baseline, 33% of whom had had a prior diagnosis. Of those with fibroids, 27% had small fibroids (<2 cm in diameter), 46% had medium (largest fibroid 2-3.9 cm in diameter), and 27% had large fibroids (largest >= 4 cm in diameter). Twenty-one percent had at least one submucosal fibroid.
MAIN RESULTS AND THE ROLE OF CHANCE: Major uterine procedures were reported by 115 women during follow-up. The estimated risk of having a procedure in any given year of follow-up for those with fibroids compared with those without fibroids increased markedly with fibroid-size category (from 4-fold, confidence interval (CI) (1.4-11.1) for the small fibroids to 10-fold, CI (4.4-24.8) for the medium fibroids, to 27-fold, CI (11.5-65.2) for the large fibroids). This influence of fibroid size on risk did not differ between African-Americans and whites (P-value for interaction = 0.88). Once fibroid size at enrollment was accounted for, having a prior diagnosis at the time of ultrasound screening was not predictive of having a procedure. Exclusion of women with a submucosal fibroid had little influence on the results. The 8-year risk of a procedure based on lifetable analyses was 2% for women with no fibroids, 8, 23, and 47%, respectively, for women who had small, medium or large fibroids at enrollment. Given the strong association of fibroid size with subsequent risk of a procedure, these findings are unlikely to be due to chance.
LIMITATIONS, REASONS FOR CAUTION: Despite a large sample size, the number of women having procedures during follow-up was relatively small. Thus, covariates such as BMI, which were not important in our analyses, may have associations that were too small to detect with our sample size. Another limitation is that the medical procedures were self-reported. However, we attempted to retrieve medical records when participants agreed, and 77% of the total procedures reported were verified. Our findings are likely to be generalizable to other African-American and white premenopausal women in their late 30s and 40s, but other ethnic groups have not been studied.
WIDER IMPLICATIONS OF THE FINDINGS: Though further studies are needed to confirm and extend the results, our findings provide an initial estimate of disease progression that will be helpful to clinicians and their patients.
C1 [Baird, D. D.] NIEHS, Epidemiol Branch, POB 12233, Res Triangle Pk, NC 27709 USA.
[Saldana, T. M.] Social & Sci Syst Inc, Durham, NC 27703 USA.
[Shore, D. L.] Westat Corp, Durham, NC 27703 USA.
[Hill, M. C.] George Washington Univ, Med Ctr, Dept Radiol, Washington, DC 20037 USA.
[Schectman, J. M.] Univ Virginia Hlth Syst, Dept Med, Charlottesville, VA 22903 USA.
RP Baird, DD (reprint author), NIEHS, Epidemiol Branch, POB 12233, Res Triangle Pk, NC 27709 USA.
EM baird@niehs.nih.gov
RI Baird, Donna/D-5214-2017
OI Baird, Donna/0000-0002-5544-2653
FU National Institute of Environmental Health Sciences; Office of Research
on Minority Health, National Institutes of Health, Health and Human
Services (IRB) [OH95-E-N048]
FX Funding came from the Intramural Research Program of the National
Institute of Environmental Health Sciences and the Office of Research on
Minority Health, National Institutes of Health, Health and Human
Services (IRB #OH95-E-N048).
NR 32
TC 2
Z9 2
U1 0
U2 4
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 DEC
PY 2015
VL 30
IS 12
BP 2936
EP 2944
DI 10.1093/humrep/dev235
PG 9
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA DB3UI
UT WOS:000368437300027
PM 26409013
ER
PT J
AU Ringeisen, H
Aldworth, J
Colpe, LJ
Pringle, B
Simile, C
AF Ringeisen, Heather
Aldworth, Jeremy
Colpe, Lisa J.
Pringle, Beverly
Simile, Catherine
TI Estimating the prevalence of any impairing childhood mental disorder in
the national health interview survey
SO INTERNATIONAL JOURNAL OF METHODS IN PSYCHIATRIC RESEARCH
LA English
DT Article
DE children; adolescents; epidemiology; estimation; methods
ID PSYCHIATRIC-ASSESSMENT CAPA; TEST-RETEST RELIABILITY; DIFFICULTIES
QUESTIONNAIRE; PSYCHOMETRIC PROPERTIES; CALIBRATION; POPULATION;
DIAGNOSES; STRENGTHS; CHILDREN; VERSION
AB This study investigates whether the six-item Strengths and Difficulties Questionnaire SDQ (five symptoms and one impact item) included in the National Health Interview Survey (NHIS) can be used to construct models that accurately estimate the prevalence of any impairing mental disorder among children 4-17 years old as measured by a shortened Child/Adolescent or Preschool Age Psychiatric Assessment (CAPA or PAPA). A subsample of 217 NHIS respondents completed a follow-up CAPA or PAPA interview. Logistic regression models were developed to model presence of any child mental disorder with impairment (MDI) or with severe impairment (MDSI). Models containing only the SDQ impact item exhibited highly biased prevalence estimates. The best-performing model included information from both the five symptom SDQ items and the impact item, where absolute bias was reduced and sensitivity and concordance were increased. This study illustrates the importance of using all available information from the six-item SDQ to accurately estimate the prevalence of any impairing childhood mental disorder from the NHIS. Copyright (C) 2015 John Wiley & Sons, Ltd.
C1 [Ringeisen, Heather; Aldworth, Jeremy] RTI Int, Res Triangle Pk, NC USA.
[Colpe, Lisa J.; Pringle, Beverly] NIMH, Bethesda, MD 20892 USA.
[Simile, Catherine] Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Hyattsville, MD 20782 USA.
RP Ringeisen, H (reprint author), RTI Int, Survey Res Div, POB 12194, Res Triangle Pk, NC 27709 USA.
EM hringeisen@rti.org
FU National Institute of Mental Health [200-2009-F-32679]; NCHS within the
Centers for Disease Control and Prevention
FX The views expressed in this manuscript do not necessarily represent the
views of the National Institutes of Health, the National Center for
Health Statistics (NCHS) or the Federal Government. This research was
supported by National Institute of Mental Health through contract
200-2009-F-32679 with the NCHS within the Centers for Disease Control
and Prevention. The authors acknowledge reviews by Joe Gfroerer, Jonaki
Bose, and Sarra Hedden from the Substance Abuse and Mental Health
Services Administration and Patricia Pastor, Marcie Cynamon, Stephen
Blumberg, and Jennifer Madans from the National Center for Health
Statistics. At RTI International, Anne Gering and Judith Cannada
provided editorial assistance and report production. The statistical
expert was Jeremy Aldworth.
NR 21
TC 0
Z9 0
U1 2
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1049-8931
EI 1557-0657
J9 INT J METH PSYCH RES
JI Int. J. Methods Psychiatr. Res.
PD DEC
PY 2015
VL 24
IS 4
BP 266
EP 274
DI 10.1002/mpr.1471
PG 9
WC Psychiatry
SC Psychiatry
GA DB3NY
UT WOS:000368419600003
PM 26202997
ER
PT J
AU Coffman, MC
Trubanova, A
Richey, JA
White, SW
Kim-Spoon, J
Ollendick, TH
Pine, DS
AF Coffman, Marika C.
Trubanova, Andrea
Richey, J. Anthony
White, Susan W.
Kim-Spoon, Jungmeen
Ollendick, Thomas H.
Pine, Daniel S.
TI Validation of the NIMH-ChEFS adolescent face stimulus set in an
adolescent, parent, and health professional sample
SO INTERNATIONAL JOURNAL OF METHODS IN PSYCHIATRIC RESEARCH
LA English
DT Article
DE adolescent development; face processing; methodology; emotion
perception; face stimulus set
ID FACIAL EXPRESSIONS; PROCESSING BIASES; EMOTIONAL FACES; SOCIAL PHOBIA;
VISUAL-SEARCH; CHILDREN; ANXIETY; ADULTS; RECOGNITION; DEPRESSION
AB Attention to faces is a fundamental psychological process in humans, with atypical attention to faces noted across several clinical disorders. Although many clinical disorders onset in adolescence, there is a lack of well-validated stimulus sets containing adolescent faces available for experimental use. Further, the images comprising most available sets are not controlled for high-and low-level visual properties. Here, we present a cross-site validation of the National Institute of Mental Health Child Emotional Faces Picture Set (NIMH-ChEFS), comprised of 257 photographs of adolescent faces displaying angry, fearful, happy, sad, and neutral expressions. All of the direct facial images from the NIMH-ChEFS set were adjusted in terms of location of facial features and standardized for luminance, size, and smoothness. Although overall agreement between raters in this study and the original development-site raters was high (89.52%), this differed by group such that agreement was lower for adolescents relative to mental health professionals in the current study. These results suggest that future research using this face set or others of adolescent/child faces should base comparisons on similarly-aged validation data. Copyright (C) 2015 John Wiley & Sons, Ltd.
C1 [Coffman, Marika C.; Trubanova, Andrea; Richey, J. Anthony; White, Susan W.; Kim-Spoon, Jungmeen; Ollendick, Thomas H.] Virginia Polytech Inst & State Univ, Dept Psychol, Blacksburg, VA 24061 USA.
[Pine, Daniel S.] NIMH, Sect Dev & Affect Neurosci, Mood Program, Intramural Res Program, Bethesda, MD 20892 USA.
[Pine, Daniel S.] NIMH, Sect Dev & Affect Neurosci, Anxiety Program, Intramural Res Program, Bethesda, MD 20892 USA.
RP Coffman, MC (reprint author), Virginia Polytech Inst & State Univ, Dept Psychol, Blacksburg, VA 24061 USA.
EM marika@vt.edu
FU National Institute of Mental Health (NIMH) [R34 MH096915]; NIMH
FX This work was supported in part by the National Institute of Mental
Health (NIMH) Grant # R34 MH096915 awarded to Thomas H. Ollendick. The
authors gratefully acknowledge the NIMH for its support and the many
colleagues who assisted them with various aspects of the present
research, including Kathleen Driscoll who helped create the surveys.
Finally, the authors thank the parents, teenagers, and colleagues who
participated in the validation ratings.
NR 43
TC 3
Z9 3
U1 3
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1049-8931
EI 1557-0657
J9 INT J METH PSYCH RES
JI Int. J. Methods Psychiatr. Res.
PD DEC
PY 2015
VL 24
IS 4
BP 275
EP 286
DI 10.1002/mpr.1490
PG 12
WC Psychiatry
SC Psychiatry
GA DB3NY
UT WOS:000368419600004
PM 26359940
ER
PT J
AU Lee, L
Igarashi, H
Fujimori, N
Hijioka, M
Kawabe, K
Oda, Y
Jensen, RT
Ito, T
AF Lee, Lingaku
Igarashi, Hisato
Fujimori, Nao
Hijioka, Masayuki
Kawabe, Ken
Oda, Yoshinao
Jensen, Robert T.
Ito, Tetsuhide
TI Long-term outcomes and prognostic factors in 78 Japanese patients with
advanced pancreatic neuroendocrine neoplasms: a single-center
retrospective study
SO JAPANESE JOURNAL OF CLINICAL ONCOLOGY
LA English
DT Article
DE pancreatic neuroendocrine neoplasms; pancreatic neuroendocrine tumor;
pancreatic neuroendocrine carcinoma; Ki-67 index; prognostic factor
ID FACTORS INFLUENCING SURVIVAL; ZOLLINGER-ELLISON-SYNDROME; ISLET-CELL
CARCINOMA; ENDOCRINE TUMORS; MITOTIC COUNT; KI-67 INDEX; PHASE-II;
EPIDEMIOLOGY; METASTASES; SYSTEM
AB Objective: Despite an increase in the number of Japanese patients with pancreatic neuroendocrine neoplasms, long-term outcomes and prognostic factors, especially for those with advanced disease, remain unclear.
Methods: We retrospectively reviewed the medical records of 78 patients with unresectable pancreatic neuroendocrine neoplasms treated at our hospital from January 1987 to March 2015. Survival analyses were performed using Kaplan-Meier methods. Prognostic significance of several clinicopathological factors were analyzed by univariate and multivariate analyses using a Cox regression model.
Results: Median overall survivals of pancreatic neuroendocrine tumor (n = 64) and pancreatic neuroendocrine carcinoma (n = 14) were 83.7 and 9.1 months, respectively (hazard ratio: 0.02, 95% confidence interval: 0.01-0.08, P < 0.001). Although no significant differences were observed using a Ki-67 cut-off value of 2% (hazard ratio: 0.46, 95% confidence interval: 0.16-1.13, P = 0.0989), a Ki-67 cut-off of 10% was a significant predictor in patients with pancreatic neuroendocrine tumor (hazard ratio: 9.95, 95% confidence interval, 3.01-32.97, P < 0.001). Treatment after the advent of targeted therapy (hazard ratio: 0.07, 95% confidence interval: 0.03-0.19, P < 0.001) and the presence of bone metastases (hazard ratio: 4.38, 95% confidence interval: 1.42-11.29, P = 0.013) were significant prognostic factors in patients with pancreatic neuroendocrine tumor evaluated by univariate analysis. Multivariate analysis also revealed that a Ki-67 index = 10% (hazard ratio: 38.8, 95% confidence interval: 8.42-226.62, P < 0.001), approval of targeted therapy (hazard ratio: 0.02, 95% confidence interval: 0.00-0.11, P < 0.001) and bone metastases (hazard ratio: 5.56, 95% confidence interval: 1.10-24.00, P = 0.039) were independent prognostic factors.
Conclusions: We elucidated the long-term outcomes and prognostic factors in Japanese patients with advanced pancreatic neuroendocrine neoplasms.
C1 [Lee, Lingaku; Igarashi, Hisato; Fujimori, Nao; Hijioka, Masayuki; Kawabe, Ken; Ito, Tetsuhide] Kyushu Univ, Grad Sch Med Sci, Dept Med & Bioregulatory Sci, Fukuoka 8128582, Japan.
[Oda, Yoshinao] Kyushu Univ, Grad Sch Med Sci, Dept Anat Pathol, Fukuoka 8128582, Japan.
[Jensen, Robert T.] NIDDK, Digest Dis Branch, NIH, Bethesda, MD 20892 USA.
RP Ito, T (reprint author), Kyushu Univ, Grad Sch Med Sci, Dept Med & Bioregulatory Sci, Higashi Ku, 3-1-1 Maidashi, Fukuoka 8128582, Japan.
EM itopapa@intmed3.med.kyushu-u.ac.jp
RI U-ID, Kyushu/C-5291-2016
FU Research Committee of Intractable Pancreatic Disease by Ministry of
Health, Labour and Welfare of Japan
FX This study was supported in part by the Research Committee of
Intractable Pancreatic Disease (Principal Investigator: Yoshifumi
Takeyama) provided by the Ministry of Health, Labour and Welfare of
Japan.
NR 56
TC 3
Z9 3
U1 0
U2 3
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0368-2811
EI 1465-3621
J9 JPN J CLIN ONCOL
JI Jpn. J. Clin. Oncol.
PD DEC
PY 2015
VL 45
IS 12
BP 1131
EP 1138
DI 10.1093/jjco/hyv143
PG 8
WC Oncology
SC Oncology
GA DB3JB
UT WOS:000368405900006
PM 26378090
ER
PT J
AU Chon, B
Tokumasu, F
Lee, JY
Allen, DW
Rice, JP
Hwang, J
AF Chon, Bonghwan
Tokumasu, Fuyuki
Lee, Ji Youn
Allen, David W.
Rice, Joseph P.
Hwang, Jeeseong
TI Digital phantoms generated by spectral and spatial light modulators
SO JOURNAL OF BIOMEDICAL OPTICS
LA English
DT Article
DE hyperspectral imaging; optical imaging standard; digital phantom; single
cell molecular imaging; scatter imaging; spatial light modulator
ID PLASMODIUM-FALCIPARUM; MALARIA PIGMENT; HEMOZOIN; SYSTEM
AB A hyperspectral image projector (HIP) based on liquid crystal on silicon spatial light modulators is explained and demonstrated to generate data cubes. The HIP-constructed data cubes are three-dimensional images of the spatial distribution of spectrally resolved abundances of intracellular light-absorbing oxyhemoglobin molecules in single erythrocytes. Spectrally and spatially resolved image data indistinguishable from the real scene may be used as standard data cubes, so-called digital phantoms, to calibrate image sensors and validate image analysis algorithms for their measurement quality, performance consistency, and interlaboratory comparisons for quantitative biomedical imaging applications. (C) 2015 Society of Photo-Optical Instrumentation Engineers (SPIE)
C1 [Chon, Bonghwan; Lee, Ji Youn; Hwang, Jeeseong] NIST, Quantum Elect & Photon Div, Boulder, CO 80305 USA.
[Tokumasu, Fuyuki] NIH, Lab Malaria & Vector Res, Bethesda, MD 20892 USA.
[Allen, David W.; Rice, Joseph P.] NIST, Sensor Sci Div, Gaithersburg, MD 20899 USA.
RP Hwang, J (reprint author), NIST, Quantum Elect & Photon Div, 325 Broadway St, Boulder, CO 80305 USA.
EM jch@nist.gov
FU NIST Innovations in Measurement Science Program on Optical Medical
Imaging for Clinical Applications and the Intramural Research Program of
the NIAID, NIH; NIST and the Intramural Program of the National
Institute for Biomedical Imaging and Bioengineering of the NIH
FX Certain commercial equipments, instruments, or materials are identified
in this paper. Such identification does not imply recommendation or
endorsement by the National Institute of Standards and Technology, nor
does it imply that the materials or equipment identified are necessarily
the best available for the purpose. This research was supported by the
NIST Innovations in Measurement Science Program on Optical Medical
Imaging for Clinical Applications and the Intramural Research Program of
the NIAID, NIH. This research was performed while J.L. held a National
Research Council Research Associateship Award at NIH (NIBIB)/NIST.
Funding for this award was provided by the NIST and the Intramural
Program of the National Institute for Biomedical Imaging and
Bioengineering of the NIH. Authors would like to thank to Dr. Kimberly
Briggman, Dr. Maritoni Litorja, and Dr. Eric Shirley at NIST, Do-Hyun
Kim at USFDA, and Stephen Kanick at Dartmouth College for valuable
discussions.
NR 31
TC 0
Z9 0
U1 2
U2 2
PU SPIE-SOC PHOTO-OPTICAL INSTRUMENTATION ENGINEERS
PI BELLINGHAM
PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA
SN 1083-3668
EI 1560-2281
J9 J BIOMED OPT
JI J. Biomed. Opt.
PD DEC
PY 2015
VL 20
IS 12
AR 121309
DI 10.1117/1.JBO.20.12.121309
PG 8
WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine &
Medical Imaging
SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine &
Medical Imaging
GA DB3VG
UT WOS:000368440300012
PM 26502383
ER
PT J
AU Ghassemi, P
Wang, JT
Melchiorri, AJ
Ramella-Roman, JC
Mathews, SA
Coburn, JC
Sorg, BS
Chen, Y
Pfefer, TJ
AF Ghassemi, Pejhman
Wang, Jianting
Melchiorri, Anthony J.
Ramella-Roman, Jessica C.
Mathews, Scott A.
Coburn, James C.
Sorg, Brian S.
Chen, Yu
Pfefer, T. Joshua
TI Rapid prototyping of biomimetic vascular phantoms for hyperspectral
reflectance imaging
SO JOURNAL OF BIOMEDICAL OPTICS
LA English
DT Article
DE three-dimensional printing; tissue phantoms; hyperspectral reflectance
imaging; oximetry
ID TISSUE OPTICAL-PROPERTIES; TURBID MEDIA; IN-VITRO; SATURATION
AB The emerging technique of rapid prototyping with three-dimensional (3-D) printers provides a simple yet revolutionary method for fabricating objects with arbitrary geometry. The use of 3-D printing for generating morphologically biomimetic tissue phantoms based on medical images represents a potentially major advance over existing phantom approaches. Toward the goal of image-defined phantoms, we converted a segmented fundus image of the human retina into a matrix format and edited it to achieve a geometry suitable for printing. Phantoms with vessel-simulating channels were then printed using a photoreactive resin providing biologically relevant turbidity, as determined by spectrophotometry. The morphology of printed vessels was validated by x-ray microcomputed tomography. Channels were filled with hemoglobin (Hb) solutions undergoing desaturation, and phantoms were imaged with a near-infrared hyperspectral reflectance imaging system. Additionally, a phantom was printed incorporating two disjoint vascular networks at different depths, each filled with Hb solutions at different saturation levels. Light propagation effects noted during these measurements-including the influence of vessel density and depth on Hb concentration and saturation estimates, and the effect of wavelength on vessel visualization depth-were evaluated. Overall, our findings indicated that 3-D-printed biomimetic phantoms hold significant potential as realistic and practical tools for elucidating light-tissue interactions and characterizing biophotonic system performance. (C) The Authors. Published by SPIE under a Creative Commons Attribution 3.0 Unported License.
C1 [Ghassemi, Pejhman; Wang, Jianting; Coburn, James C.; Pfefer, T. Joshua] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA.
[Wang, Jianting; Melchiorri, Anthony J.; Chen, Yu] Univ Maryland, Fischell Dept Bioengn, College Pk, MD 20742 USA.
[Ramella-Roman, Jessica C.] Florida Int Univ, Dept Biomed Engn, Miami, FL 33174 USA.
[Ramella-Roman, Jessica C.] Florida Int Univ, Herbert Wertheim Coll Med, Miami, FL 33174 USA.
[Mathews, Scott A.] Catholic Univ Amer, Dept Elect Engn & Comp Sci, Washington, DC 20064 USA.
[Sorg, Brian S.] NCI, NIH, Rockville, MD 20852 USA.
RP Pfefer, TJ (reprint author), US FDA, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA.
EM Joshua.Pfefer@fda.hhs.gov
FU Food and Drug Administration (FDA) Critical Path Initiative; National
Science Foundation's FDA Scholar-in-Residence program (NSF)
[CBET-1238407]; University of Maryland's Center for Excellence in
Regulatory Science and Innovation
FX The authors would like to thank Dr. Srinidhi Nagaraja, Dr. Maureen
Dreher, and Dr. Maria Iacono for their help with mu-CT imaging and 3-D
visualization. The authors gratefully acknowledge funding support from
the Food and Drug Administration (FDA) Critical Path Initiative, the
National Science Foundation's FDA Scholar-in-Residence program (NSF,
CBET-1238407), and the University of Maryland's Center for Excellence in
Regulatory Science and Innovation.
NR 29
TC 2
Z9 2
U1 1
U2 5
PU SPIE-SOC PHOTO-OPTICAL INSTRUMENTATION ENGINEERS
PI BELLINGHAM
PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98225 USA
SN 1083-3668
EI 1560-2281
J9 J BIOMED OPT
JI J. Biomed. Opt.
PD DEC
PY 2015
VL 20
IS 12
AR 121312
DI 10.1117/1.JBO.20.12.121312
PG 10
WC Biochemical Research Methods; Optics; Radiology, Nuclear Medicine &
Medical Imaging
SC Biochemistry & Molecular Biology; Optics; Radiology, Nuclear Medicine &
Medical Imaging
GA DB3VG
UT WOS:000368440300015
PM 26662064
ER
PT J
AU Aufforth, RD
Ramakant, P
Sadowski, SM
Mehta, A
Trebska-McGowan, K
Nilubol, N
Pacak, K
Kebebew, E
AF Aufforth, Rachel D.
Ramakant, Pooja
Sadowski, Samira M.
Mehta, Amit
Trebska-McGowan, Katarzyna
Nilubol, Naris
Pacak, Karel
Kebebew, Electron
TI Pheochromocytoma Screening Initiation and Frequency in von Hippel-Lindau
Syndrome
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID DISEASE; NORMETANEPHRINE; METANEPHRINE
AB Context: Patients with von Hippel-Lindau (VHL) syndrome have a 25-30% chance of developing pheochromocytoma. Although practice guidelines recommend biochemical and radiological screening every 1-2 years for pheochromocytoma in patients with VHL, there are limited data on the optimal age and frequency for screening.
Objective: Our objective was to determine the earliest age of onset and frequency of contralateral and recurrent pheochromocytomas in patients with VHL syndrome.
Methods: This is a retrospective analysis of a prospective cohort of patients with VHL enrolled in a natural history study.
Results: A total of 273 patients diagnosed with VHL were enrolled in a natural history clinical study. Thirty-one percent (84) were diagnosed with pheochromocytoma. The mean age of diagnosis was 28.8 +/- 13.9 years. The earliest age at diagnosis was 5.5 years. Median follow-up for the cohort was 116.6 months (range, 0.1-613.2). Ninety-nine percent (83) of patients underwent adrenalectomy. Fifty-eight and 32% of patients had metanephrines and/or catecholamines elevated more than two times and more than four times the upper limit of normal, respectively. Twenty-five percent (21) of pheochromocytomas were diagnosed in pediatric patients younger than 19 years of age, and 86% and 57% of pediatric patients had an elevation more than two times and more than four times upper limit of normal, respectively. Eight patients had a total of nine recurrences. The median age at recurrence was 33.5 years (range, 8.8-51.9). Recurrences occurred as short as 0.5 years and as long as 39.7 years after the initial operation.
Conclusions: Our findings among VHL pediatric patients supports the need for biochemical screening starting at age 5 with annual lifelong screening.
C1 [Aufforth, Rachel D.; Sadowski, Samira M.; Nilubol, Naris; Kebebew, Electron] NCI, Endocrine Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Ramakant, Pooja] Christian Med Coll & Hosp, Dept Endocrine Surg, Vellore, Tamil Nadu, India.
[Mehta, Amit] Geisel Sch Med, Hanover, NH USA.
[Trebska-McGowan, Katarzyna] NCI, Thorac & Gastrointestinal Oncol Branch, Bethesda, MD 20892 USA.
[Pacak, Karel] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD 20892 USA.
RP Kebebew, E (reprint author), NCI, Endocrine Oncol Branch, Bethesda, MD 20892 USA.
EM kebebewe@mail.nih.gov
FU intramural research programs of the Center for Cancer Research, National
Cancer Institute, National Institutes of Health
FX This research was supported by the intramural research programs of the
Center for Cancer Research, National Cancer Institute, National
Institutes of Health.
NR 21
TC 2
Z9 2
U1 0
U2 4
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 DEC
PY 2015
VL 100
IS 12
BP 4498
EP 4504
DI 10.1210/jc.2015-3045
PG 7
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA DB3RI
UT WOS:000368428600030
PM 26451910
ER
PT J
AU Rampling, T
Ewer, K
Bowyer, G
Wright, D
Venkatraman, N
Payne, R
Nicosia, A
Sullivan, N
Graham, B
Pollard, A
Draper, S
Ballou, R
Lawrie, A
Gilbert, S
Hill, A
AF Rampling, Tommy
Ewer, Katie
Bowyer, Georgina
Wright, Danny
Venkatraman, Navin
Payne, Ruth
Nicosia, Alfredo
Sullivan, Nancy
Graham, Barney
Pollard, Andrew
Draper, Simon
Ballou, Ripley
Lawrie, Alison
Gilbert, Sarah
Hill, Adrian
TI SAFETY AND IMMUNOGENICITY OF THE HETEROLOGOUS PRIME-BOOST EBOLAVIRUS
VACCINE REGIMEN CHAD3-EBO Z AND MVA-BN (R) FILO IN HEALTHY UK ADULTS
SO JOURNAL OF INFECTION
LA English
DT Meeting Abstract
C1 [Rampling, Tommy; Ewer, Katie; Bowyer, Georgina; Wright, Danny; Venkatraman, Navin; Payne, Ruth; Pollard, Andrew; Draper, Simon; Lawrie, Alison; Gilbert, Sarah; Hill, Adrian] Univ Oxford, Oxford, England.
[Sullivan, Nancy; Graham, Barney] NIAID, Rockville, MD USA.
[Ballou, Ripley] GlaxoSmithkline, Rixensart, Belgium.
[Nicosia, Alfredo] ReiThera, Rome, Italy.
RI Ewer, Katie/B-4328-2011
OI Ewer, Katie/0000-0001-9827-9836
NR 0
TC 0
Z9 0
U1 0
U2 1
PU W B SAUNDERS CO LTD
PI LONDON
PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND
SN 0163-4453
EI 1532-2742
J9 J INFECTION
JI J. Infect.
PD DEC
PY 2015
VL 71
IS 6
BP 688
EP 688
DI 10.1016/j.jinf.2015.09.031
PG 1
WC Infectious Diseases
SC Infectious Diseases
GA DB4JZ
UT WOS:000368480600022
ER
PT J
AU Peng, YH
Shen, DG
Liao, S
Turkbey, B
Rais-Bahrami, S
Wood, B
Karademir, I
Antic, T
Yousef, A
Jiang, YL
Pinto, PA
Choyke, PL
Oto, A
AF Peng, Yahui
Shen, Dinggang
Liao, Shu
Turkbey, Baris
Rais-Bahrami, Soroush
Wood, Bradford
Karademir, Ibrahim
Antic, Tatjana
Yousef, Ambereen
Jiang, Yulei
Pinto, Peter A.
Choyke, Peter L.
Oto, Aytekin
TI MRI-Based Prostate Volume-Adjusted Prostate-Specific Antigen in the
Diagnosis of Prostate Cancer
SO JOURNAL OF MAGNETIC RESONANCE IMAGING
LA English
DT Article
ID TRANSITION ZONE VOLUME; RADICAL PROSTATECTOMY; TRANSRECTAL ULTRASOUND;
SPECIMEN VOLUMES; GLEASON SCORE; PSA DENSITY; HYPERPLASIA; MEN; TRIAL;
NG/ML
AB Purpose: To determine whether prostate-specific antigen (PSA) levels adjusted by prostate and zonal volumes estimated from magnetic resonance imaging (MRI) improve the diagnosis of prostate cancer (PCa) and differentiation between patients who harbor high-Gleason-sum PCa and those without PCa.
Materials and Methods: This retrospective study was Health Insurance Portability and Accountability Act (HIPAA)-compliant and approved by the Institutional Review Board of participating medical institutions. T-2-weighted MR images were acquired for 61 PCa patients and 100 patients with elevated PSA but without PCa. Computer methods were used to segment prostate and zonal structures and to estimate the total prostate and central-gland (CG) volumes, which were then used to calculate CG volume fraction, PSA density, and PSA density adjusted by CG volume. These quantities were used to differentiate patients with and without PCa. Area under the receiver operating characteristic curve (AUC) was used as the figure of merit.
Results: The total prostate and CG volumes, CG volume fraction, and PSA density adjusted by the total prostate and CG volumes were statistically significantly different between patients with PCa and patients without PCa (P <= 0.007). AUC values for the total prostate and CG volumes, and PSA density adjusted by CG volume, were 0.68 +/- 0.04, 0.68 +/- 0.04, and 0.66 +/- 0.04, respectively, and were significantly better than that of PSA (P< 0.02), for differentiation of PCa patients from patients without PCa.
Conclusion: The total prostate and CG volumes estimated from T-2-weighted MR images and PSA density adjusted by these volumes can improve the effectiveness of PSA for the diagnosis of PCa and differentiation of high-Gleason-sum PCa patients from patients without PCa.
C1 [Peng, Yahui] Beijing Jiaotong Univ, Sch Elect & Informat Engn, Beijing 100044, Peoples R China.
[Peng, Yahui; Karademir, Ibrahim; Yousef, Ambereen; Jiang, Yulei; Oto, Aytekin] Univ Chicago, Dept Radiol, Chicago, IL 60637 USA.
[Shen, Dinggang; Liao, Shu] Univ N Carolina, Dept Radiol, Chapel Hill, NC USA.
[Turkbey, Baris] Natl Canc Inst, NIH, Mol Imaging Program, Bethesda, MD USA.
[Rais-Bahrami, Soroush; Wood, Bradford; Pinto, Peter A.] Natl Canc Inst, NIH, Urol Oncol Branch, Bethesda, MD USA.
[Antic, Tatjana] Univ Chicago, Dept Pathol, Chicago, IL 60637 USA.
[Choyke, Peter L.] NIH, Dept Diagnost Radiol, Bethesda, MD 20892 USA.
RP Peng, YH (reprint author), Beijing Jiaotong Univ, Sch Elect & Informat Engn, 3 Shangyuancun, Beijing 100044, Peoples R China.
EM yhpeng@bjtu.edu.cn
OI Rais-Bahrami, Soroush/0000-0001-9466-9925
FU US Army Medical Research and Materiel Command Prostate Cancer Research
Program; Idea Development Award [PC093485]; Beijing Jiaotong University
Talent Fund [2014RC044]
FX Contract grant sponsor: US Army Medical Research and Materiel Command
Prostate Cancer Research Program; Contract grant number: Idea
Development Award PC093485; Contract grant sponsor: Beijing Jiaotong
University Talent Fund; Contract grant number: 2014RC044.
NR 41
TC 3
Z9 3
U1 2
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1053-1807
EI 1522-2586
J9 J MAGN RESON IMAGING
JI J. Magn. Reson. Imaging
PD DEC
PY 2015
VL 42
IS 6
BP 1733
EP 1739
DI 10.1002/jmri.24944
PG 7
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA DB1HD
UT WOS:000368258100030
PM 25946664
ER
PT J
AU Siglinsky, E
Krueger, D
Ward, RE
Caserotti, P
Strotmeyer, ES
Harris, TB
Binkley, N
Buehring, B
AF Siglinsky, E.
Krueger, D.
Ward, R. E.
Caserotti, P.
Strotmeyer, E. S.
Harris, T. B.
Binkley, N.
Buehring, B.
TI Effect of age and sex on jumping mechanography and other measures of
muscle mass and function
SO JOURNAL OF MUSCULOSKELETAL & NEURONAL INTERACTIONS
LA English
DT Article
DE Aging; Skeletal Muscle; Sarcopenia; Jumping Mechanography; Muscle
Function Tests
ID LOWER-EXTREMITY FUNCTION; PHYSICAL PERFORMANCE BATTERY; X-RAY
ABSORPTIOMETRY; OLDER-ADULTS; BODY-COMPOSITION; SUBSEQUENT DISABILITY;
WALKING SPEED; GAIT SPEED; SARCOPENIA; POWER
AB Objectives: Sarcopenia increases falls and fracture risk. Sarcopenia clinical trials require robust quantitative tools to evaluate muscle function; jumping mechanography (JM) is likely one such tool. However, US data comparing JM with traditional tests across the lifespan is limited. This study evaluated the effect of age and sex on JM compared with traditional function tests and lean mass. Methods: US adults (213 women/119 men; mean age 65.4 years, range 27-96) performed functional tests including JM, Short Physical Performance Battery (SPPB) and grip strength (GS). Appendicular lean mass (ALM) was measured using DXA. Results: Men had higher relative jump power [mean (SD) 28.5 (10.52) vs. 21.9 (7.11) W/kg], GS [35.5 (9.84) vs. 22.7 (6.98) kg] and ALM/ht(2) [8.25 (1.35) vs. 6.99 (1.38) kg/m(2)] (all p< 0.0001); no difference was observed for SPPB components. JM parameters were more strongly correlated with age than traditional tests (R-2= 0.38-0.61 vs. R-2= 0.01-0.28) and weakly with GS and chair rise time (R-2= 0.30-0.36). Conclusion: JM parameters are correlated with GS and chair rise time and demonstrate stronger correlations with age. JM shows promise as a valuable tool to evaluate and monitor interventions for sarcopenia as it could potentially detect change in muscle function more precisely than existing tools.
C1 [Siglinsky, E.; Krueger, D.; Binkley, N.; Buehring, B.] Univ Wisconsin, Osteoporosis Clin Res Program, Madison, WI 53705 USA.
[Ward, R. E.] Spaulding Rehabil Hosp, Cambridge, MA USA.
[Ward, R. E.] Boston Univ, Sch Publ Hlth, Boston, MA USA.
[Caserotti, P.] Univ Southern Denmark, Odense, Denmark.
[Strotmeyer, E. S.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Ctr Aging & Populat Hlth, Pittsburgh, PA USA.
[Harris, T. B.] NIA, Bethesda, MA USA.
[Buehring, B.] William S Middleton Mem Vet Adm Med Ctr, Madison, WI USA.
RP Buehring, B (reprint author), Univ Wisconsin, Osteoporosis Clin Res Program, 2870 Univ Ave,Suite 100, Madison, WI 53705 USA.
EM bbuehring@medicine.wisc.edu
RI Buehring, Bjoern/L-5581-2013;
OI Buehring, Bjoern/0000-0003-3841-624X; Strotmeyer,
Elsa/0000-0002-4093-6036
FU National Institute on Aging [P01-AG020166]; General Clinical Research
Centers Program; National Center for Advancing Translational Sciences
(NCATS), National Institutes of Health [UL1TR000427]; Merck Co., Inc.
FX The MIDUS research is supported by a grant from the National Institute
on Aging (P01-AG020166). The research was further supported by the
General Clinical Research Centers Program and UL1TR000427 (UW) from the
National Center for Advancing Translational Sciences (NCATS), National
Institutes of Health". Jump Validation and Vitamin D studies at the
University of Wisconsin sponsored by an investigator initiated research
grant from Merck & Co., Inc.
NR 43
TC 3
Z9 3
U1 2
U2 7
PU JMNI
PI NAFPLION
PA 7 SPILIADOU SQ, NAFPLION, 21 100, GREECE
SN 1108-7161
J9 J MUSCULOSKEL NEURON
JI J. Musculoskelet. Neuronal Interact.
PD DEC
PY 2015
VL 15
IS 4
BP 301
EP 308
PG 8
WC Neurosciences; Physiology
SC Neurosciences & Neurology; Physiology
GA DB1CF
UT WOS:000368244900001
PM 26636275
ER
PT J
AU Sorond, FA
Cruz-Almeida, Y
Clark, DJ
Viswanathan, A
Scherzer, CR
De Jager, P
Csiszar, A
Laurienti, PJ
Hausdorff, JM
Chen, WG
Ferrucci, L
Rosano, C
Studenski, SA
Black, SE
Lipsitz, LA
AF Sorond, Farzaneh A.
Cruz-Almeida, Yenisel
Clark, David J.
Viswanathan, Anand
Scherzer, Clemens R.
De Jager, Philip
Csiszar, Anna
Laurienti, Paul J.
Hausdorff, Jeffery M.
Chen, Wen G.
Ferrucci, Luiggi
Rosano, Caterina
Studenski, Stephanie A.
Black, Sandra E.
Lipsitz, Lewis A.
TI Aging, the Central Nervous System, and Mobility in Older Adults: Neural
Mechanisms of Mobility Impairment
SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL
SCIENCES
LA English
DT Article
DE CNS; Aging; Mobility; Imaging
ID SMALL VESSEL DISEASE; VASCULAR COGNITIVE IMPAIRMENT; WHITE-MATTER
LESIONS; CEREBROVASCULAR HEMODYNAMICS; ISCHEMIC-STROKE; GAIT SPEED;
CADASIL; ASSOCIATION; PLASTICITY; WALKING
AB Background. Mobility is crucial for successful aging and is impaired in many older adults. We know very little about the subtle, subclinical age-related changes in the central nervous system (CNS) that mediate mobility impairment.
Methods. A conference series focused on aging, the CNS, and mobility was launched. The second conference addressed major age-associated mechanisms of CNS-mediated mobility impairment. Speakers and conference attendees recommended key areas for future research, identified barriers to progress, and proposed strategies to overcome them.
Results. Priorities identified for future research include (a) studying interactions among different mechanisms; (b) examining effects of interventions targeting these mechanisms; (c) evaluating the effect of genetic polymorphisms on risks and course of age-related mobility impairment; and (d) examining the effect of age on CNS repair processes, neuroplasticity, and neuronal compensatory mechanisms. Key strategies to promote research include (a) establish standard measures of mobility across species; (b) evaluate the effect of aging in the absence of disease on CNS and mobility; and (c) use advanced computational methods to better evaluate the interactions between CNS and other systems involved in mobility.
Conclusions. CNS is a major player in the process, leading to mobility decline with aging. Future research in this area has the potential to prolong independence in older persons. Better interactions among disciplines and shared research paradigms are needed to make progress. Research priorities include the development of innovative approaches to integrate research on aging, cognition, and movement with attention to neurovascular function, neuroplasticity, and neurophysiological reserve.
C1 [Sorond, Farzaneh A.] Brigham & Womens Hosp, Stroke Div, Dept Neurol, Boston, MA 02115 USA.
[Cruz-Almeida, Yenisel] Univ Florida, Coll Med, Dept Aging & Geriatr Res, Inst Aging, Gainesville, FL USA.
[Clark, David J.] Univ Florida, Dept Aging & Geriatr Res, North Florida South Georgia Vet Hlth Syst, Brain Rehabil Res Ctr, Gainesville, FL USA.
[Viswanathan, Anand] Harvard Univ, Sch Med, Dept Neurol, Stroke Div,Massachusetts Gen Hosp, Boston, MA 02115 USA.
[Scherzer, Clemens R.; De Jager, Philip] Harvard Univ, Brigham & Womens Hosp, Dept Neurol, Sch Med, Boston, MA 02115 USA.
[Csiszar, Anna] Univ Oklahoma, Hlth Sci Center, Reynolds Oklahoma Ctr Aging, Dept Geriatr Med, Norman, OK 73019 USA.
[Laurienti, Paul J.] Wake Forest Sch Med, Dept Radiol, Winston Salem, NC USA.
[Hausdorff, Jeffery M.] Tel Aviv Univ, Tel Aviv Sourasky Med Ctr, Dept Med, IL-69978 Tel Aviv, Israel.
[Chen, Wen G.] NIA, Sensory & Motor Disorders Aging, Bethesda, MD 20892 USA.
[Ferrucci, Luiggi] NIA, Longitudinal Studies Sect, Bethesda, MD 20892 USA.
[Rosano, Caterina] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15260 USA.
[Studenski, Stephanie A.] Pittsburgh Healthcare Syst, Div Geriatr Med, Dept Med, Pittsburgh, PA USA.
[Black, Sandra E.] Univ Toronto, Sunnybrook Res Inst, Dept Neurol, Toronto, ON M5S 1A1, Canada.
[Lipsitz, Lewis A.] Harvard Univ, Sch Med, Hebrew Senior Life, Inst Aging Res,Res, Boston, MA USA.
RP Sorond, FA (reprint author), Brigham & Womens Hosp, Stroke Div, Dept Neurol, 75 Francis St, Boston, MA 02115 USA.
EM fsorond@partners.org
OI Rosano, Caterina/0000-0002-0909-1506; Rosano,
Caterina/0000-0002-4271-6010
FU National Institute on Aging [U13-AG-041613-01, T32-AG-000181];
University of Pittsburgh Claude D. Pepper Older Americans Independence
Center (National Institute on Aging) [P30-AG-024827]; [RO1-NS-085002]
FX This work was supported by a cooperative conference grant (National
Institute on Aging, U13-AG-041613-01), the University of Pittsburgh
Claude D. Pepper Older Americans Independence Center (National Institute
on Aging, P30-AG-024827), a postdoctoral training grant (National
Institute on Aging, T32-AG-000181), and RO1-NS-085002.
NR 45
TC 6
Z9 6
U1 2
U2 8
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 DEC
PY 2015
VL 70
IS 12
BP 1526
EP 1532
DI 10.1093/gerona/glv130
PG 7
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA DB2UB
UT WOS:000368364100009
PM 26386013
ER
PT J
AU Marcum, ZA
Perera, S
Newman, AB
Thorpe, JM
Switzer, GE
Gray, SL
Simonsick, EM
Shorr, RI
Bauer, DC
Castle, NG
Studenski, SA
Hanlon, JT
AF Marcum, Zachary A.
Perera, Subashan
Newman, Anne B.
Thorpe, Joshua M.
Switzer, Galen E.
Gray, Shelly L.
Simonsick, Eleanor M.
Shorr, Ronald I.
Bauer, Douglas C.
Castle, Nicholas G.
Studenski, Stephanie A.
Hanlon, Joseph T.
CA Hlth ABC Study
TI Antihypertensive Use and Recurrent Falls in Community-Dwelling Older
Adults: Findings From the Health ABC Study
SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL
SCIENCES
LA English
DT Article
DE Falls; Medication; Epidemiology; Drug related
ID BODY-COMPOSITION; DRUG-USE; HYPERTENSION; MEDICATIONS; RISK; PREDICTORS;
FRACTURES; PEOPLE; ELDERS; AGE
AB Background. Despite wide-spread use of antihypertensives in older adults, the literature is unclear about their association with incident recurrent falls over time.
Methods. Health, Aging and Body Composition study participants (n = 2,948) who were well functioning at baseline (1997) were followed to Year 7 (2004). The main outcome was recurrent falls (>= 2) in the ensuing 12 months. Antihypertensive use was examined as: (a) any versus none, (b) long-versus short-term (<= 2 vs <2 years), and by (c) summated standardized daily dose (SDD; 1 = maximum recommended daily dose for one antihypertensive), and (d) subclass.
Results. Controlling for potential demographic, health status/behavior and access to care confounders, we found no increase in risk of recurrent falls in antihypertensive users compared to nonusers (adjusted odds ratio [AOR] = 1.13; 95% CI = 0.88-1.46), or those taking higher SDDs or for longer durations. Only those using a loop diuretic were found to have a modest increased risk of recurrent falls (AOR = 1.50; 95% CI = 1.11-2.03).
Conclusions. Antihypertensive use overall was not statistically significantly associated with recurrent falls after adjusting for important confounders. Loop diuretic use may be associated with recurrent falls and needs further study.
C1 [Marcum, Zachary A.; Perera, Subashan; Newman, Anne B.; Hanlon, Joseph T.; Hlth ABC Study] Univ Pittsburgh, Dept Geriatr Med, Pittsburgh, PA 15260 USA.
[Perera, Subashan; Hanlon, Joseph T.] Univ Pittsburgh, Dept Biostat, Pittsburgh, PA 15260 USA.
[Newman, Anne B.; Hanlon, Joseph T.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15260 USA.
[Thorpe, Joshua M.; Hanlon, Joseph T.] Univ Pittsburgh, Dept Pharm & Therapeut, Pittsburgh, PA 15260 USA.
[Thorpe, Joshua M.; Switzer, Galen E.] Vet Affairs Pittsburgh Healthcare Syst, Ctr Hlth Equity Res, Pittsburgh, PA USA.
[Switzer, Galen E.] Univ Pittsburgh, Dept Med Gen Internal, Pittsburgh, PA 15260 USA.
[Switzer, Galen E.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 15260 USA.
[Gray, Shelly L.] Univ Washington, Sch Pharm, Seattle, WA 98195 USA.
[Simonsick, Eleanor M.] NIA, Intramural Res Program, Baltimore, MD 21224 USA.
[Shorr, Ronald I.] North Florida South Georgia Vet Hlth Syst GRECC, Gainesville, FL USA.
[Bauer, Douglas C.] Univ Calif San Francisco, Div Gen Internal Med, San Francisco, CA 94143 USA.
[Castle, Nicholas G.] Univ Pittsburgh, Dept Hlth Policy & Management, Pittsburgh, PA 15260 USA.
[Hanlon, Joseph T.] Vet Affairs Pittsburgh Healthcare Syst, GRECC, Pittsburgh, PA USA.
RP Marcum, ZA (reprint author), Univ Washington, Sch Pharm, Dept Pharm, 1959 NE Pacific St,Box 357630, Seattle, WA 98195 USA.
EM zmarcum@uw.edu
RI Newman, Anne B./C-6408-2013
OI Newman, Anne B./0000-0002-0106-1150
FU National Institute on Aging (NIA) [R01AG027017, P30AG024827,
T32AG021885, K07AG033174]; Intramural Research program of the National
Institutes of Health [N01AG62101, N01AG62103, N01AG62106, R01AG028050];
National Institute of Nursing Research grant [R01NR012459]
FX This work was supported by National Institute on Aging (NIA) grants
(R01AG027017, P30AG024827, T32AG021885, and K07AG033174). This work was
also supported in part by the Intramural Research program of the
National Institutes of Health (N01AG62101, N01AG62103, N01AG62106, and
R01AG028050) and a National Institute of Nursing Research grant
(R01NR012459).
NR 33
TC 0
Z9 0
U1 2
U2 3
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 DEC
PY 2015
VL 70
IS 12
BP 1562
EP 1568
DI 10.1093/gerona/glv095
PG 7
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA DB2UB
UT WOS:000368364100014
PM 26265732
ER
PT J
AU Patel, AV
Johansson, G
Colbert, MC
Dasgupta, B
Ratner, N
AF Patel, Ami V.
Johansson, Gunnar
Colbert, Melissa C.
Dasgupta, Biplab
Ratner, Nancy
TI Fatty acid synthase is a metabolic oncogene targetable in malignant
peripheral nerve sheath tumors
SO NEURO-ONCOLOGY
LA English
DT Article
DE C75; FASN; lipid droplet; MPNST; sarcoma
ID SCHWANN-CELL DEVELOPMENT; BREAST-CANCER CELLS; NEURAL CREST; THERAPEUTIC
TARGET; INHIBITION; NEUROFIBROMATOSIS; C75; DIFFERENTIATION;
MAINTENANCE; PROGRESSION
AB Background. Malignant peripheral nerve sheath tumors (MPNSTs) are soft tissue sarcomas with minimal therapeutic opportunities. We observed that lipid droplets (LDs) accumulate in human MPNST cell lines and in primary human tumor samples. The goal of this study was to investigate the relevance of lipid metabolism to MPNST survival and as a possible therapeutic target.
Methods. Based on preliminary findings that MPNSTs accumulate LDs, we hypothesized that a deregulated lipid metabolism supports MPNST cell survival/proliferation rate. To test this, we examined respiration, role of fatty acid oxidation (FAO), and the enzyme fatty acid synthase involved in de novo fatty acid synthesis in MPNSTs using both genetic and pharmacological tools.
Results. We demonstrate that LDs accumulate in MPNST cell lines, primary human and mouse MPNST tumors, and neural crest cells. LDs from MPNST cells disappear on lipid deprivation, indicating that LDs can be oxidized as a source of energy. Inhibition of FAO decreased oxygen consumption and reduced MPNST survival, indicating that MPNST cells likely metabolize LDs through active FAO. FAO inhibition reduced oxygen consumption and survival even in the absence of exogenous lipids, indicating that lipids synthesized de novo can also be oxidized. Consequently, inhibition of de novo fatty acid synthesis, which is overexpressed in human MPNST cell lines, effectively reduced MPNST survival and delayed induction of tumor growth in vivo.
Conclusion. Our results show that MPNSTs depend on lipid metabolic pathways and suggest that disrupting lipid metabolism could be a potential new strategy for the development of MPNST therapeutics.
C1 [Patel, Ami V.; Ratner, Nancy] Childrens Hosp Med Ctr, Div Expt Hematol & Canc Biol, 3333 Burnet Ave,MLC 7013, Cincinnati, OH 45229 USA.
[Dasgupta, Biplab] Cincinnati Childrens Hosp, Div Oncol, Cincinnati, OH USA.
[Johansson, Gunnar] Umea Univ, Dept Radiat Sci, Oncol, Umea, Sweden.
[Colbert, Melissa C.] Natl Inst Hlth, Compliance, Off Intramural Res, Bethesda, MD 20892 USA.
RP Ratner, N (reprint author), Childrens Hosp Med Ctr, Div Expt Hematol & Canc Biol, 3333 Burnet Ave,MLC 7013, Cincinnati, OH 45229 USA.
EM nancy.ratner@cchmc.org
FU Cancer Free Kids Grant [R01NS075291-01]; DAMD Program on
Neurofibromatosis Postdoctoral Fellowship [W81XWH1110144]; Pelotonia
Postdoctoral Award
FX This work was supported by a grant from Cancer Free Kids Grant for N.R.
R01NS075291-01 to B.D. A.V.P. received funding from the DAMD Program on
Neurofibromatosis Postdoctoral Fellowship W81XWH1110144 and a Pelotonia
Postdoctoral Award.
NR 40
TC 4
Z9 4
U1 0
U2 0
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 DEC
PY 2015
VL 17
IS 12
BP 1599
EP 1608
DI 10.1093/neuonc/nov076
PG 10
WC Oncology; Clinical Neurology
SC Oncology; Neurosciences & Neurology
GA DB3ZO
UT WOS:000368452700008
PM 26116612
ER
PT J
AU Sharpe, MJ
Wikenheiser, AM
Niv, Y
Schoenbaum, G
AF Sharpe, Melissa J.
Wikenheiser, Andrew M.
Niv, Yael
Schoenbaum, Geoffrey
TI The State of the Orbitofrontal Cortex
SO NEURON
LA English
DT Editorial Material
ID BEHAVIOR; RATS
AB State representation is fundamental to behavior. However, identifying the true state of the world is challenging when explicit cues are ambiguous. Here, Bradfield and colleagues show that the medial OFC is critical for using associative information to discriminate ambiguous states.
C1 [Sharpe, Melissa J.; Wikenheiser, Andrew M.; Schoenbaum, Geoffrey] NIDA, Baltimore, MD 21224 USA.
[Sharpe, Melissa J.; Niv, Yael] Princeton Univ, Princeton Neurosci Inst, Princeton, NJ 08544 USA.
[Niv, Yael] Princeton Univ, Dept Psychol, Princeton, NJ 08544 USA.
[Schoenbaum, Geoffrey] Univ Maryland, Sch Med, Dept Anat & Neurobiol, Baltimore, MD 21201 USA.
[Schoenbaum, Geoffrey] Johns Hopkins Univ, Solomon H Snyder Dept Neurosci, Baltimore, MD 21218 USA.
RP Sharpe, MJ (reprint author), NIDA, Baltimore, MD 21224 USA.
EM melissa.sharpe@nih.gov; geoffrey.schoenbaum@nih.gov
NR 14
TC 2
Z9 2
U1 3
U2 8
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 0896-6273
EI 1097-4199
J9 NEURON
JI Neuron
PD DEC
PY 2015
VL 88
IS 6
BP 1075
EP 1077
DI 10.1016/j.neuron.2015.12.004
PG 4
WC Neurosciences
SC Neurosciences & Neurology
GA DB3WM
UT WOS:000368443900004
PM 26687216
ER
PT J
AU Gearhart, PJ
Castiblanco, DP
Knode, LMR
AF Gearhart, Patricia J.
Castiblanco, Diana P.
Knode, Lisa M. Russell
TI Exceptional Antibodies Produced by Successive Immunizations
SO PLOS BIOLOGY
LA English
DT Article
ID BROADLY NEUTRALIZING ANTIBODIES; SOMATIC HYPERMUTATION;
MONOCLONAL-ANTIBODIES; VACCINE DEVELOPMENT; SEQUENCING REVEALS;
IMMUNOGEN DESIGN; SUPER-ENHANCERS; VARIABLE GENES; HIV-1 VACCINE;
B-CELLS
AB Antibodies stand between us and pathogens. Viruses mutate quickly to avoid detection, and antibodies mutate at similar rates to hunt them down. This death spiral is fueled by specialized proteins and error-prone polymerases that change DNA sequences. Here, we explore how B lymphocytes stay in the race by expressing activation-induced deaminase, which unleashes a tsunami of mutations in the immunoglobulin loci. This produces random DNA substitutions, followed by selection for the highest affinity antibodies. We may be able to manipulate the process to produce better antibodies by expanding the repertoire of specific B cells through successive vaccinations.
C1 [Gearhart, Patricia J.; Castiblanco, Diana P.; Knode, Lisa M. Russell] NIA, Lab Mol Biol & Immunol, NIH, Baltimore, MD 21224 USA.
RP Gearhart, PJ (reprint author), NIA, Lab Mol Biol & Immunol, NIH, Baltimore, MD 21224 USA.
EM gearhartp@mail.nih.gov
FU Intramural Research program of the NIH, National Institute on Aging
[AG000714]
FX This work was supported entirely by the Intramural Research program of
the NIH, National Institute on Aging, AG000714. The funders had no role
in study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 44
TC 0
Z9 0
U1 0
U2 5
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1545-7885
J9 PLOS BIOL
JI PLoS. Biol.
PD DEC
PY 2015
VL 13
IS 12
AR e1002321
DI 10.1371/journal.pbio.1002321
PG 7
WC Biochemistry & Molecular Biology; Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics
GA DB3WE
UT WOS:000368443000013
PM 26641938
ER
PT J
AU Hall, M
Woolhouse, M
Rambaut, A
AF Hall, Matthew
Woolhouse, Mark
Rambaut, Andrew
TI Epidemic Reconstruction in a Phylogenetics Framework: Transmission Trees
as Partitions of the Node Set
SO PLOS COMPUTATIONAL BIOLOGY
LA English
DT Article
ID PATHOGENIC AVIAN INFLUENZA; HEPATITIS-C VIRUS; RELAXED PHYLOGENETICS;
DISEASE TRANSMISSION; MITOCHONDRIAL-DNA; TIME-ESTIMATION; SEQUENCE DATA;
GENETIC DATA; INFERENCE; OUTBREAKS
AB The use of genetic data to reconstruct the transmission tree of infectious disease epidemics and outbreaks has been the subject of an increasing number of studies, but previous approaches have usually either made assumptions that are not fully compatible with phylogenetic inference, or, where they have based inference on a phylogeny, have employed a procedure that requires this tree to be fixed. At the same time, the coalescent-based models of the pathogen population that are employed in the methods usually used for time-resolved phylogeny reconstruction are a considerable simplification of epidemic process, as they assume that pathogen lineages mix freely. Here, we contribute a new method that is simultaneously a phylogeny reconstruction method for isolates taken from an epidemic, and a procedure for transmission tree reconstruction. We observe that, if one or more samples is taken from each host in an epidemic or outbreak and these are used to build a phylogeny, a transmission tree is equivalent to a partition of the set of nodes of this phylogeny, such that each partition element is a set of nodes that is connected in the full tree and contains all the tips corresponding to samples taken from one and only one host. We then implement a Monte Carlo Markov Chain (MCMC) procedure for simultaneous sampling from the spaces of both trees, utilising a newly-designed set of phylogenetic tree proposals that also respect node partitions. We calculate the posterior probability of these partitioned trees based on a model that acknowledges the population structure of an epidemic by employing an individual-based disease transmission model and a coalescent process taking place within each host. We demonstrate our method, first using simulated data, and then with sequences taken from the H7N7 avian influenza outbreak that occurred in the Netherlands in 2003. We show that it is superior to established coalescent methods for reconstructing the topology and node heights of the phylogeny and performs well for transmission tree reconstruction when the phylogeny is well-resolved by the genetic data, but caution that this will often not be the case in practice and that existing genetic and epidemiological data should be used to configure such analyses whenever possible. This method is available for use by the research community as part of BEAST, one of the most widely-used packages for reconstruction of dated phylogenies.
C1 [Hall, Matthew; Woolhouse, Mark; Rambaut, Andrew] Univ Edinburgh, Inst Evolutionary Biol, Edinburgh, Midlothian, Scotland.
[Hall, Matthew; Woolhouse, Mark; Rambaut, Andrew] Univ Edinburgh, Ctr Immun Infect & Evolut, Edinburgh, Midlothian, Scotland.
[Rambaut, Andrew] NIH, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA.
RP Hall, M (reprint author), Univ Edinburgh, Inst Evolutionary Biol, Edinburgh, Midlothian, Scotland.
EM m.d.hall@sms.ed.ac.uk
FU Scottish Government [EPIC II RA1651 544MWX]; European Research Council
under the European Community [278433-PREDEMICS]; ERC [260864]
FX MH was supported by a Ph.D. studentship from the Scottish
Government-funded EPIC (Epidemiology, Population Health and Infectious
Disease Control) program under grant number EPIC II RA1651 544MWX
(http://epicscotland.org/). AR has received funding from the European
Research Council under the European Community's Seventh Framework
Programme (FP7/2007-2013) under Grant Agreement no. 278433-PREDEMICS and
ERC Grant agreement no. 260864
(http://cordis.europa.eu/fp7/home_en.html). The funders had no role in
study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 54
TC 9
Z9 9
U1 1
U2 9
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 DEC
PY 2015
VL 11
IS 12
AR e1004613
DI 10.1371/journal.pcbi.1004613
PG 36
WC Biochemical Research Methods; Mathematical & Computational Biology
SC Biochemistry & Molecular Biology; Mathematical & Computational Biology
GA DB4ZJ
UT WOS:000368521900022
PM 26717515
ER
PT J
AU Arimbasseri, AG
Blewett, NH
Iben, JR
Lamichhane, TN
Cherkasova, V
Hafner, M
Maraia, RJ
AF Arimbasseri, Aneeshkumar G.
Blewett, Nathan H.
Iben, James R.
Lamichhane, Tek N.
Cherkasova, Vera
Hafner, Markus
Maraia, Richard J.
TI RNA Polymerase III Output Is Functionally Linked to tRNA Dimethyl-G26
Modification
SO PLOS GENETICS
LA English
DT Article
ID SACCHAROMYCES-CEREVISIAE; SCHIZOSACCHAROMYCES-POMBE; NONSENSE
SUPPRESSION; DIVERSE SIGNALS; GROWTH-CONTROL; FISSION YEAST; MAF1;
TRANSCRIPTION; PROTEIN; TRANSLATION
AB Control of the differential abundance or activity of tRNAs can be important determinants of gene regulation. RNA polymerase (RNAP) III synthesizes all tRNAs in eukaryotes and it derepression is associated with cancer. Maf1 is a conserved general repressor of RNAP III under the control of the target of rapamycin (TOR) that acts to integrate transcriptional output and protein synthetic demand toward metabolic economy. Studies in budding yeast have indicated that the global tRNA gene activation that occurs with derepression of RNAP III via maf1-deletion is accompanied by a paradoxical loss of tRNA-mediated nonsense suppressor activity, manifested as an antisuppression phenotype, by an unknown mechanism. We show that maf1-antisuppression also occurs in the fission yeast S. pombe amidst general activation of RNAP III. We used tRNA-HydroSeq to document that little changes occurred in the relative levels of different tRNAs in maf1 Delta cells. By contrast, the efficiency of N2, N2-dimethyl G26 (m(2)(2)G26) modification on certain tRNAs was decreased in response to maf1-deletion and associated with antisuppression, and was validated by other methods. Over-expression of Trm1, which produces m(2)(2)G26, reversed maf1-antisuppression. A model that emerges is that competition by increased tRNA levels in maf1 Delta cells leads to m(2)(2)G26 hypomodification due to limiting Trm1, reducing the activity of suppressor-tRNASerUCA and accounting for antisuppression. Consistent with this, we show that RNAP III mutations associated with hypomyelinating leukodystrophy decrease tRNA transcription, increase m(2)(2)G26 efficiency and reverse antisuppression. Extending this more broadly, we show that a decrease in tRNA synthesis by treatment with rapamycin leads to increased m(2)(2)G26 modification and that this response is conserved among highly divergent yeasts and human cells.
C1 [Arimbasseri, Aneeshkumar G.; Blewett, Nathan H.; Iben, James R.; Lamichhane, Tek N.; Cherkasova, Vera] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Intramural Res Program, NIH, Bethesda, MD USA.
[Hafner, Markus] NIAMSD, NIH, Bethesda, MD 20892 USA.
[Maraia, Richard J.] US PHS, Commissioned Corps, Washington, DC USA.
RP Arimbasseri, AG (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Intramural Res Program, NIH, Bethesda, MD USA.
EM maraiar@mail.nih.gov
OI Arimbasseri, Gopalakrishnan Aneeshkumar/0000-0001-5266-2688
FU Intramural Research Programs of the Eunice Kennedy Shriver National
Institute of Child Health and Human Development; National Institute of
Arthritis and Musculoskeletal and Skin Diseases, NIH [HD000412-28]
FX This work was supported by the Intramural Research Programs of the
Eunice Kennedy Shriver National Institute of Child Health and Human
Development and the National Institute of Arthritis and Musculoskeletal
and Skin Diseases, NIH. The Grant number is HD000412-28. The URL of
funders website is
http://data.nidb.nih.gov/reports/viewreports.taf?ipid=90327&ts=144061033
6. The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 61
TC 8
Z9 8
U1 1
U2 2
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 DEC
PY 2015
VL 11
IS 12
AR e1005671
DI 10.1371/journal.pgen.1005671
PG 22
WC Genetics & Heredity
SC Genetics & Heredity
GA DB4YB
UT WOS:000368518400014
PM 26720005
ER
PT J
AU Liu, Y
Singh, SR
Zeng, XK
Zhao, JS
Hou, SX
AF Liu, Ying
Singh, Shree Ram
Zeng, Xiankun
Zhao, Jiangsha
Hou, Steven X.
TI The Nuclear Matrix Protein Megator Regulates Stem Cell Asymmetric
Division through the Mitotic Checkpoint Complex in Drosophila Testes
SO PLOS GENETICS
LA English
DT Article
ID SPINDLE ASSEMBLY CHECKPOINT; SOMATIC SUPPORT CELLS; SELF-RENEWAL;
TRANSGENIC RNAI; PORE COMPLEX; GENE-EXPRESSION; GERM-CELLS; POLE BODY;
NICHE; TPR
AB In adult Drosophila testis, asymmetric division of germline stem cells (GSCs) is specified by an oriented spindle and cortically localized adenomatous coli tumor suppressor homolog 2 (Apc2). However, the molecular mechanism underlying these events remains unclear. Here we identified Megator (Mtor), a nuclear matrix protein, which regulates GSC maintenance and asymmetric division through the spindle assembly checkpoint (SAC) complex. Loss of Mtor function results in Apc2 mis-localization, incorrect centrosome orientation, defective mitotic spindle formation, and abnormal chromosome segregation that lead to the eventual GSC loss. Expression of mitotic arrest-deficient-2 (Mad2) and monopolar spindle 1 (Mps1) of the SAC complex effectively rescued the GSC loss phenotype associated with loss of Mtor function. Collectively our results define a new role of the nuclear matrix-SAC axis in regulating stem cell maintenance and asymmetric division.
C1 [Liu, Ying; Singh, Shree Ram; Zeng, Xiankun; Zhao, Jiangsha; Hou, Steven X.] NCI, Basic Res Lab, NIH, Frederick, MD 21701 USA.
RP Liu, Y (reprint author), NCI, Basic Res Lab, NIH, Frederick, MD 21701 USA.
EM hous@mail.nih.gov
RI Singh, Shree Ram/B-7614-2008; Liu, Ying /K-8883-2016
OI Singh, Shree Ram/0000-0001-6545-583X;
FU National Cancer Institute, National Institutes of Health
FX This research was supported by the Intramural Research Program of the
National Cancer Institute, National Institutes of Health. The funders
had no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 60
TC 1
Z9 1
U1 3
U2 4
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 DEC
PY 2015
VL 11
IS 12
AR e1005750
DI 10.1371/journal.pgen.1005750
PG 20
WC Genetics & Heredity
SC Genetics & Heredity
GA DB4YB
UT WOS:000368518400073
PM 26714316
ER
PT J
AU Pineda, S
Real, FX
Kogevinas, M
Carrato, A
Chanock, SJ
Malats, N
Van Steen, K
AF Pineda, Silvia
Real, Francisco X.
Kogevinas, Manolis
Carrato, Alfredo
Chanock, Stephen J.
Malats, Nuria
Van Steen, Kristel
TI Integration Analysis of Three Omics Data Using Penalized Regression
Methods: An Application to Bladder Cancer
SO PLOS GENETICS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; GENE-EXPRESSION; DNA METHYLATION; ELASTIC-NET;
LOCI; SELECTION; VARIANTS; PROTEINS; BIOLOGY; REVEAL
AB Omics data integration is becoming necessary to investigate the genomic mechanisms involved in complex diseases. During the integration process, many challenges arise such as data heterogeneity, the smaller number of individuals in comparison to the number of parameters, multicollinearity, and interpretation and validation of results due to their complexity and lack of knowledge about biological processes. To overcome some of these issues, innovative statistical approaches are being developed. In this work, we propose a permutation-based method to concomitantly assess significance and correct by multiple testing with the MaxT algorithm. This was applied with penalized regression methods (LASSO and ENET) when exploring relationships between common genetic variants, DNA methylation and gene expression measured in bladder tumor samples. The overall analysis flow consisted of three steps: (1) SNPs/CpGs were selected per each gene probe within 1Mb window upstream and downstream the gene; (2) LASSO and ENET were applied to assess the association between each expression probe and the selected SNPs/CpGs in three multivariable models (SNP, CPG, and Global models, the latter integrating SNPs and CPGs); and (3) the significance of each model was assessed using the permutation-based MaxT method. We identified 48 genes whose expression levels were significantly associated with both SNPs and CPGs. Importantly, 36 (75%) of them were replicated in an independent data set (TCGA) and the performance of the proposed method was checked with a simulation study. We further support our results with a biological interpretation based on an enrichment analysis. The approach we propose allows reducing computational time and is flexible and easy to implement when analyzing several types of omics data. Our results highlight the importance of integrating omics data by applying appropriate statistical strategies to discover new insights into the complex genetic mechanisms involved in disease conditions.
C1 [Pineda, Silvia; Malats, Nuria] Spanish Natl Canc Res Ctr CNIO, Genet & Mol Epidemiol Grp, Madrid, Spain.
[Pineda, Silvia; Van Steen, Kristel] Univ Liege, Inst Montefiore, Syst & Modeling Unit, BIO3, B-4000 Liege, Belgium.
[Real, Francisco X.] Spanish Natl Canc Res Ctr CNIO, Epithelial Carcinogenesis Grp, Madrid, Spain.
[Real, Francisco X.] Univ Pompeu Fabra, Dept Ciencies Expt & Salut, Barcelona, Spain.
[Kogevinas, Manolis] Ctr Res Environm Epidemiol CREAL, Barcelona, Spain.
[Carrato, Alfredo] Hosp Univ Ramon & Cajal, Serv Oncol, Madrid, Spain.
[Carrato, Alfredo] Hosp Univ Elche, Serv Oncol, Alicante, Spain.
[Chanock, Stephen J.] NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Van Steen, Kristel] GIGA R, Syst Biol & Chem Biol, Liege, Belgium.
RP Pineda, S (reprint author), Spanish Natl Canc Res Ctr CNIO, Genet & Mol Epidemiol Grp, Madrid, Spain.
EM nmalats@cnio.es; kristel.vansteen@ulg.ac.be
RI Kogevinas, Manolis/C-3918-2017; Real, Francisco X/H-5275-2015;
OI Real, Francisco X/0000-0001-9501-498X; Malats, Nuria/0000-0003-2538-3784
FU Fondo de Investigaciones Sanitarias (FIS), Instituto de Salud Carlos
III, Spain [PI06-1614, PI12-00815]; Red Tematica de Investigacion
Cooperativa en Cancer, Spain [RD12/0036/0034, RD12/0036/0050];
EU-FP7-HEALTH [F2-2008-201663-UROMOL, F2-2008-201333-DECanBio]; USA-NIH
[RO1-CA089715, NO2-CP-11015]; European Cooperation in Science and
Technology (COST Action) [BM1204: EU_Pancreas]; Obra Social Fundacion
"la Caixa"
FX The work was partially supported by Fondo de Investigaciones Sanitarias
(FIS), Instituto de Salud Carlos III, Spain (#PI06-1614 and
#PI12-00815); Red Tematica de Investigacion Cooperativa en Cancer, Spain
(#RD12/0036/0034 and #RD12/0036/0050); EU-FP7-HEALTH
(F2-2008-201663-UROMOL and F2-2008-201333-DECanBio); USA-NIH
(RO1-CA089715 and NO2-CP-11015); and European Cooperation in Science and
Technology (COST Action #BM1204: EU_Pancreas). SP was funded by a Obra
Social Fundacion "la Caixa". The funders had no role in study design,
data collection and analysis, decision to publish, or preparation of the
manuscript.
NR 47
TC 4
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U1 1
U2 9
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1553-7404
J9 PLOS GENET
JI PLoS Genet.
PD DEC
PY 2015
VL 11
IS 12
AR e1005689
DI 10.1371/journal.pgen.1005689
PG 22
WC Genetics & Heredity
SC Genetics & Heredity
GA DB4YB
UT WOS:000368518400024
PM 26646822
ER
PT J
AU Yuen, CM
Kurbatova, EV
Tupasi, T
Caoili, JC
Van der Walt, M
Kvasnovsky, C
Yagui, M
Bayona, J
Contreras, C
Leimane, V
Ershova, J
Via, LE
Kim, H
Akksilp, S
Kazennyy, BY
Volchenkov, GV
Jou, R
Kliiman, K
Demikhova, OV
Vasilyeva, IA
Dalton, T
Cegielski, JP
AF Yuen, Courtney M.
Kurbatova, Ekaterina V.
Tupasi, Thelma
Caoili, Janice Campos
Van der Walt, Martie
Kvasnovsky, Charlotte
Yagui, Martin
Bayona, Jaime
Contreras, Carmen
Leimane, Vaira
Ershova, Julia
Via, Laura E.
Kim, HeeJin
Akksilp, Somsak
Kazennyy, Boris Y.
Volchenkov, Grigory V.
Jou, Ruwen
Kliiman, Kai
Demikhova, Olga V.
Vasilyeva, Irina A.
Dalton, Tracy
Cegielski, J. Peter
TI Association between Regimen Composition and Treatment Response in
Patients with Multidrug-Resistant Tuberculosis: A Prospective Cohort
Study
SO PLOS MEDICINE
LA English
DT Article
ID SPUTUM CULTURE CONVERSION; AGGRESSIVE REGIMENS; DRUG-RESISTANCE;
2ND-LINE DRUGS; PREDICTORS; OUTCOMES; SUSCEPTIBILITY; PYRAZINAMIDE; 1ST
AB Background
For treating multidrug-resistant tuberculosis (MDR TB), the World Health Organization (WHO) recommends a regimen of at least four second-line drugs that are likely to be effective as well as pyrazinamide. WHO guidelines indicate only marginal benefit for regimens based directly on drug susceptibility testing (DST) results. Recent evidence from isolated cohorts suggests that regimens containing more drugs may be beneficial, and that DST results are predictive of regimen effectiveness. The objective of our study was to gain insight into how regimen design affects treatment response by analyzing the association between time to sputum culture conversion and both the number of potentially effective drugs included in a regimen and the DST results of the drugs in the regimen.
Methods and Findings
We analyzed data from the Preserving Effective Tuberculosis Treatment Study (PETTS), a prospective observational study of 1,659 adults treated for MDR TB during 2005-2010 in nine countries: Estonia, Latvia, Peru, Philippines, Russian Federation, South Africa, South Korea, Thailand, and Taiwan. For all patients, monthly sputum samples were collected, and DST was performed on baseline isolates at the US Centers for Disease Control and Prevention. We included 1,137 patients in our analysis based on their having known baseline DST results for at least fluoroquinolones and second-line injectable drugs, and not having extensively drug-resistant TB. These patients were followed for a median of 20 mo (interquartile range 16-23 mo) after MDR TB treatment initiation. The primary outcome of interest was initial sputum culture conversion. We used Cox proportional hazards regression, stratifying by country to control for setting-associated confounders, and adjusting for the number of drugs to which patients' baseline isolates were resistant, baseline resistance pattern, previous treatment history, sputum smear result, and extent of disease on chest radiograph.
In multivariable analysis, receiving an average of at least six potentially effective drugs (defined as drugs without a DST result indicating resistance) per day was associated with a 36% greater likelihood of sputum culture conversion than receiving an average of at least five but fewer than six potentially effective drugs per day (adjusted hazard ratio [aHR] 1.36, 95% CI 1.09-1.69). Inclusion of pyrazinamide (aHR 2.00, 95% CI 1.65-2.41) or more drugs to which baseline DST indicated susceptibility (aHR 1.65, 95% CI 1.48-1.84, per drug) in regimens was associated with greater increases in the likelihood of sputum culture conversion than including more drugs to which baseline DST indicated resistance (aHR 1.33, 95% CI 1.18-1.51, per drug). Including in the regimen more drugs for which DST was not performed was beneficial only if a minimum of three effective drugs was present in the regimen (aHR 1.39, 95% CI 1.09-1.76, per drug when three effective drugs present in regimen).
The main limitation of this analysis is that it is based on observational data, not a randomized trial, and drug regimens varied across sites. However, PETTS was a uniquely large and rigorous observational study in terms of both the number of patients enrolled and the standardization of laboratory testing. Other limitations include the assumption of equivalent efficacy across drugs in a category, incomplete data on adherence, and the fact that the analysis considers only initial sputum culture conversion, not reversion or long-term relapse.
Conclusions
MDR TB regimens including more potentially effective drugs than the minimum of five currently recommended by WHO may encourage improved response to treatment in patients with MDR TB. Rapid access to high-quality DST results could facilitate the design of more effective individualized regimens. Randomized controlled trials are necessary to confirm whether individualized regimens with more than five drugs can indeed achieve better cure rates than current recommended regimens.
C1 [Yuen, Courtney M.; Kurbatova, Ekaterina V.; Caoili, Janice Campos; Kvasnovsky, Charlotte; Ershova, Julia; Dalton, Tracy; Cegielski, J. Peter] Ctr Dis Control & Prevent, Atlanta, GA USA.
[Tupasi, Thelma; Caoili, Janice Campos] Trop Dis Fdn, Manila, Philippines.
[Van der Walt, Martie; Kvasnovsky, Charlotte] MRC, Pretoria, South Africa.
[Yagui, Martin] Natl Inst Hlth, Lima, Peru.
[Bayona, Jaime] Partners Hlth, Boston, MA USA.
[Contreras, Carmen] Socios Salud Sucursal, Lima, Peru.
[Leimane, Vaira] Riga East Univ Hosp Ctr TB & Lung Dis, Riga, Latvia.
[Via, Laura E.] NIAID, NIH, Bethesda, MD 20892 USA.
[Kim, HeeJin] Korean Inst TB, Seoul, South Korea.
[Akksilp, Somsak] Minist Publ Hlth, Dept Dis Control, Bangkok, Thailand.
[Kazennyy, Boris Y.] Orel Oblast TB Dispensary, Oryol, Russia.
[Volchenkov, Grigory V.] Vladimir Oblast TB Dispensary, Vladimir, Russia.
[Jou, Ruwen] Taiwan Ctr Dis Control, Taipei, Taiwan.
[Kliiman, Kai] Tartu Univ Hosp, Tartu, Estonia.
[Demikhova, Olga V.; Vasilyeva, Irina A.] Russian Acad Med Sci, Cent TB Res Inst, Moscow, Russia.
RP Yuen, CM (reprint author), Ctr Dis Control & Prevent, Atlanta, GA USA.
EM gzc2@cdc.gov
FU U.S. Agency for International Development; U.S. Centers for Disease
Control and Prevention (CDC); U.S. National Institutes of Health's
Division of Intramural Research of the National Institute for Allergy
and Infectious Diseases; Korean Ministry of Health and Welfare
FX This work was supported by the U.S. Agency for International
Development, U.S. Centers for Disease Control and Prevention (CDC), U.S.
National Institutes of Health's Division of Intramural Research of the
National Institute for Allergy and Infectious Diseases, and the Korean
Ministry of Health and Welfare. CDC Division of Tuberculosis Elimination
led the study design, training for data collection and monitoring, data
analysis, data interpretation, and writing of the report. Other sponsors
had no roles in these activities. The views and opinions expressed in
this article are those of the authors and do not necessarily represent
an official position of the U.S. Centers for Disease Control and
Prevention.
NR 21
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U1 4
U2 5
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 DEC
PY 2015
VL 12
IS 12
AR e1001932
DI 10.1371/journal.pmed.1001932
PG 18
WC Medicine, General & Internal
SC General & Internal Medicine
GA DB3YZ
UT WOS:000368451100020
PM 26714320
ER
PT J
AU Al-Hamdan, NA
Panackal, AA
Al Bassam, TH
Alrabea, A
Al Hazmi, M
Al Mazroa, Y
Al Jefri, M
Khan, AS
Ksiazek, TG
AF Al-Hamdan, Nasser A.
Panackal, Anil A.
Al Bassam, Tami H.
Alrabea, Abdullah
Al Hazmi, Mohammed
Al Mazroa, Yagoub
Al Jefri, Mohammed
Khan, Ali S.
Ksiazek, Thomas G.
TI The Risk of Nosocomial Transmission of Rift Valley Fever
SO PLOS NEGLECTED TROPICAL DISEASES
LA English
DT Article
ID SAUDI-ARABIA; EBOLA; EPIDEMIC; VIRUS; EGYPT
AB In 2000, we investigated the Rift Valley fever (RVF) outbreak on the Arabian Peninsulathe first outside Africa-and the risk of nosocomial transmission. In a cross-sectional design, during the peak of the epidemic at its epicenter, we found four (0.6%) of 703 healthcare workers (HCWs) IgM seropositive but all with only community-associated exposures. Standard precautions are sufficient for HCWs exposed to known RVF patients, in contrast to other viral hemorrhagic fevers (VHF) such as Ebola virus disease (EVD) in which the route of transmission differs. Suspected VHF in which the etiology is uncertain should be initially managed with the most cautious infection control measures.
C1 [Al-Hamdan, Nasser A.] King Saud bin Abdulaziz Univ Hlth Sci, Fac Med, King Fahad Med City, Riyadh, Saudi Arabia.
[Panackal, Anil A.] Ctr Dis Control & Prevent CDC, USPHS, Atlanta, GA USA.
[Al Bassam, Tami H.] Hafr Albatin Hlth Reg, Hafr Albatin, Saudi Arabia.
[Alrabea, Abdullah] Kahramanmaras Sutcu Imam Univ, Coll Med, Riyadh, Saudi Arabia.
[Al Hazmi, Mohammed] King Fahad Cent Hosp, Jazan, Saudi Arabia.
[Al Mazroa, Yagoub] Minist Hlth, Hlth Serv Council, Riyadh, Saudi Arabia.
[Al Jefri, Mohammed] Minist Hlth, Dept Prevent Med, Riyadh, Saudi Arabia.
[Khan, Ali S.] Univ Nebraska Med Ctr, Coll Publ Hlth, Omaha, NE USA.
[Ksiazek, Thomas G.] Univ Texas Med Branch, Dept Pathol, Galveston Natl Lab, Galveston, TX 77555 USA.
RP Al-Hamdan, NA (reprint author), NIAID, LCID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM nalhamdan@kfmc.med.sa
FU NIH, NIAID; King Saud bin Abdulaziz University for Health Sciences,
Riyadh, Kingdom of Saudi Arabia
FX This research was supported in part (decision to publish and preparation
of manuscript) by the Intramural Research Program of the NIH, NIAID and
King Saud bin Abdulaziz University for Health Sciences, Riyadh, Kingdom
of Saudi Arabia; the funders had no role in study design or data
collection and analysis.
NR 16
TC 0
Z9 1
U1 0
U2 2
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 DEC
PY 2015
VL 9
IS 12
AR e0004314
DI 10.1371/journal.pntd.0004314
PG 6
WC Infectious Diseases; Parasitology; Tropical Medicine
SC Infectious Diseases; Parasitology; Tropical Medicine
GA DB2NG
UT WOS:000368345100060
PM 26694834
ER
PT J
AU Cangalaya, C
Zimic, M
Marzal, M
Gonzalez, AE
Guerra-Giraldez, C
Mahanty, S
Nash, TE
Garcia, HH
AF Cangalaya, Carla
Zimic, Mirko
Marzal, Miguel
Gonzalez, Armando E.
Guerra-Giraldez, Cristina
Mahanty, Siddhartha
Nash, Theodore E.
Garcia, Hector H.
CA Cysticercosis Working Grp Peru
TI Inflammation Caused by Praziquantel Treatment Depends on the Location of
the Taenia solium Cysticercus in Porcine Neurocysticercosis
SO PLOS NEGLECTED TROPICAL DISEASES
LA English
DT Article
ID BLOOD-BRAIN-BARRIER; JUNCTIONAL COMPLEX PROTEINS; MURINE
NEUROCYSTICERCOSIS; SYMPTOMATIC NEUROCYSTICERCOSIS; DIFFERENTIAL
CHANGES; COMPUTED-TOMOGRAPHY; HISTOPATHOLOGY; DISEASE; CNS
AB Background
Neurocysticercosis (NCC), infection of the central nervous system by Taenia solium cysticerci, is a pleomorphic disease. Inflammation around cysticerci is the major cause of disease but is variably present. One factor modulating the inflammatory responses may be the location and characteristics of the brain tissue adjacent to cysticerci. We analyzed and compared the inflammatory responses to cysticerci located in the parenchyma to those in the meninges or cysticerci partially in contact with both the parenchyma and the meninges (corticomeningeal).
Methodology/Principal Findings
Histological specimens of brain cysticerci (n = 196) from 11 pigs naturally infected with Taenia solium cysticerci were used. Four pigs were sacrificed after 2 days and four after 5 days of a single dose of praziquantel; 3 pigs did not receive treatment. All pigs were intravenously injected with Evans Blue to assess disruption of the blood-brain barrier. The degree of inflammation was estimated by use of a histological score (ISC) based on the extent of the inflammation in the pericystic areas as assessed in an image composed of several photomicrographs taken at 40X amplification. Parenchymal cysticerci provoked a significantly greater level of pericystic inflammation (higher ISC) after antiparasitic treatment compared to meningeal and corticomeningeal cysticerci. ISC of meningeal cysticerci was not significantly affected by treatment. In corticomeningeal cysticerci, the increase in ISC score was correlated to the extent of the cysticercus adjacent to the brain parenchyma. Disruption of the blood-brain barrier was associated with treatment only in parenchymal tissue.
Significance
Inflammatory response to cysticerci located in the meninges was significantly decreased compared to parenchymal cysticerci. The suboptimal inflammatory response to cysticidal drugs may be the reason subarachnoid NCC is generally refractory to treatment compared to parenchymal NCC.
C1 [Cangalaya, Carla; Marzal, Miguel; Guerra-Giraldez, Cristina; Mahanty, Siddhartha; Nash, Theodore E.] Univ Peruana Cayetano Heredia, Fac Ciencias & Filosofia, Lab Inmunopatol Neurocisticercosis, Lima, Peru.
[Zimic, Mirko] Univ Peruana Cayetano Heredia, Fac Ciencias & Filosofia, Lab Bioinformat & Biol Mol, Lima, Peru.
[Zimic, Mirko; Guerra-Giraldez, Cristina; Garcia, Hector H.] Univ Peruana Cayetano Heredia, Fac Ciencias & Filosofia, Dept Ciencias Celulares & Mol, Lima, Peru.
[Gonzalez, Armando E.] Univ Nacl Mayor San Marcos, Fac Med Vet, Lima 14, Peru.
[Mahanty, Siddhartha; Nash, Theodore E.] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
[Garcia, Hector H.] Inst Nacl Ciencias Neurol, Unidad Cisticercosis, Lima, Peru.
RP Cangalaya, C (reprint author), Univ Peruana Cayetano Heredia, Fac Ciencias & Filosofia, Lab Inmunopatol Neurocisticercosis, Lima, Peru.
EM carla.cangalaya.l@upch.pe
OI Cangalaya, Carla/0000-0002-3525-8445; Guerra-Giraldez,
Cristina/0000-0002-9287-9838; Mahanty, Siddhartha/0000-0003-1068-0524
FU Fogarty International Center, National Institutes of health, USA [D43
TW001140, 2D43 TW007393]; Intramural Research Program of the National
Institute of Allergy and Infectious Diseases
FX This work was partially supported by grants D43 TW001140 and 2D43
TW007393 from the Fogarty International Center, National Institutes of
health, USA, and by the Intramural Research Program of the National
Institute of Allergy and Infectious Diseases. The funders had no role in
study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 32
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U1 1
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 DEC
PY 2015
VL 9
IS 12
AR e0004207
DI 10.1371/journal.pntd.0004207
PG 13
WC Infectious Diseases; Parasitology; Tropical Medicine
SC Infectious Diseases; Parasitology; Tropical Medicine
GA DB2NG
UT WOS:000368345100014
PM 26658257
ER
PT J
AU Hostetler, JB
Sharma, S
Bartholdson, SJ
Wright, GJ
Fairhurst, RM
Rayner, JC
AF Hostetler, Jessica B.
Sharma, Sumana
Bartholdson, S. Josefin
Wright, Gavin J.
Fairhurst, Rick M.
Rayner, Julian C.
TI A Library of Plasmodium vivax Recombinant Merozoite Proteins Reveals New
Vaccine Candidates and Protein-Protein Interactions
SO PLOS NEGLECTED TROPICAL DISEASES
LA English
DT Article
ID DUFFY BINDING-PROTEIN; APICAL MEMBRANE ANTIGEN-1; DETERGENT-RESISTANT
MICRODOMAINS; TRANSMISSION-BLOCKING VACCINE; NATURALLY ACQUIRED
ANTIBODIES; HUMORAL IMMUNE-RESPONSES; MONTANIDE ISA 51; SURFACE
PROTEIN-3; PROTECTIVE EFFICACY; MALARIA PARASITES
AB Background
A vaccine targeting Plasmodium vivax will be an essential component of any comprehensive malaria elimination program, but major gaps in our understanding of P. vivax biology, including the protein-protein interactions that mediate merozoite invasion of reticulocytes, hinder the search for candidate antigens. Only one ligand-receptor interaction has been identified, that between P. vivax Duffy Binding Protein (PvDBP) and the erythrocyte Duffy Antigen Receptor for Chemokines (DARC), and strain-specific immune responses to PvDBP make it a complex vaccine target. To broaden the repertoire of potential P. vivax merozoite-stage vaccine targets, we exploited a recent breakthrough in expressing fulllength ectodomains of Plasmodium proteins in a functionally-active form in mammalian cells and initiated a large-scale study of P. vivax merozoite proteins that are potentially involved in reticulocyte binding and invasion.
Methodology/Principal Findings
We selected 39 P. vivax proteins that are predicted to localize to the merozoite surface or invasive secretory organelles, some of which show homology to P. falciparum vaccine candidates. Of these, we were able to express 37 full-length protein ectodomains in a mammalian expression system, which has been previously used to express P. falciparum invasion ligands such as PfRH5. To establish whether the expressed proteins were correctly folded, we assessed whether they were recognized by antibodies from Cambodian patients with acute vivax malaria. IgG from these samples showed at least a two-fold change in reactivity over naive controls in 27 of 34 antigens tested, and the majority showed heat-labile IgG immunoreactivity, suggesting the presence of conformation-sensitive epitopes and native tertiary protein structures. Using a method specifically designed to detect low-affinity, extracellular protein-protein interactions, we confirmed a predicted interaction between P. vivax 6-cysteine proteins P12 and P41, further suggesting that the proteins are natively folded and functional. This screen also identified two novel protein-protein interactions, between P12 and PVX_110945, and between MSP3.10 and MSP7.1, the latter of which was confirmed by surface plasmon resonance.
Conclusions/Significance We produced a new library of recombinant full-length P. vivax ectodomains, established that the majority of them contain tertiary structure, and used them to identify predicted and novel protein-protein interactions. As well as identifying new interactions for further biological studies, this library will be useful in identifying P. vivax proteins with vaccine potential, and studying P. vivax malaria pathogenesis and immunity.
Trial Registration
ClinicalTrials.gov NCT00663546
C1 [Hostetler, Jessica B.; Fairhurst, Rick M.] NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA.
[Hostetler, Jessica B.; Sharma, Sumana; Bartholdson, S. Josefin; Wright, Gavin J.; Rayner, Julian C.] Wellcome Trust Sanger Inst, Malaria Programme, Cambridge, England.
[Sharma, Sumana; Bartholdson, S. Josefin; Wright, Gavin J.] Wellcome Trust Sanger Inst, Cell Surface Signalling Lab, Cambridge, England.
RP Hostetler, JB (reprint author), NIAID, Lab Malaria & Vector Res, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM rfairhurst@niaid.nih.gov; jr9@sanger.ac.uk
OI Rayner, Julian/0000-0002-9835-1014
FU National Institute of Allergy and Infectious Diseases, National
Institutes of Health; Wellcome Trust [090851]; UK Medical Research
Council [MR/J002283/1]
FX This work was funded by the Intramural Research Program of the National
Institute of Allergy and Infectious Diseases, National Institutes of
Health, the Wellcome Trust (grant number 090851), and the UK Medical
Research Council (grant number MR/J002283/1). The funders had no role in
study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 107
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U1 4
U2 12
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 DEC
PY 2015
VL 9
IS 12
AR e0004264
DI 10.1371/journal.pntd.0004264
PG 24
WC Infectious Diseases; Parasitology; Tropical Medicine
SC Infectious Diseases; Parasitology; Tropical Medicine
GA DB2NG
UT WOS:000368345100039
PM 26701602
ER
PT J
AU Lord, JS
Gurley, ES
Pulliam, JRC
AF Lord, Jennifer S.
Gurley, Emily S.
Pulliam, Juliet R. C.
TI Rethinking Japanese Encephalitis Virus Transmission: A Framework for
Implicating Host and Vector Species
SO PLOS NEGLECTED TROPICAL DISEASES
LA English
DT Article
ID WEST-NILE-VIRUS; CULEX-TRITAENIORHYNCHUS; INFECTION; CULICIDAE; DIPTERA;
INDIA; HETEROGENEITY; BANGLADESH; EMERGENCE; MOSQUITOS
C1 [Lord, Jennifer S.] Univ Liverpool, Liverpool Sch Trop Med, Vector Grp, Liverpool L3 5QA, Merseyside, England.
[Lord, Jennifer S.; Pulliam, Juliet R. C.] Univ Florida, Dept Biol, Gainesville, FL USA.
[Gurley, Emily S.] Icddr B, Ctr Communicable Dis, Dhaka, Bangladesh.
[Pulliam, Juliet R. C.] Univ Florida, Emerging Pathogens Inst, Gainesville, FL USA.
[Pulliam, Juliet R. C.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Lord, JS (reprint author), Univ Liverpool, Liverpool Sch Trop Med, Vector Grp, Liverpool L3 5QA, Merseyside, England.
EM jennifer.suzanne.lord@gmail.com
RI Pulliam, Juliet/A-6516-2008; Gurley, Emily/B-7903-2010
OI Pulliam, Juliet/0000-0003-3314-8223; Gurley, Emily/0000-0002-8648-9403
FU Emerging Pathogens Institute, University of Florida; Research and Policy
for Infectious Disease Dynamics (RAPIDD) program; Research and Policy on
Infectious Disease Dynamics (RAPIDD) Program of the Fogarty
International Center, National Institutes of Health and Science and
Technology Directorate, Department of Homeland Security
FX At the time of writing this manuscript JSL was a postdoctoral research
associate in the Pulliam Lab at the University of Florida. We would like
to acknowledge the Emerging Pathogens Institute, University of Florida
for funding fieldwork, which contributed to the ideas within this
manuscript. We would also like to acknowledge funding for a Japanese
encephalitis workshop held in October 2012 by the Research and Policy
for Infectious Disease Dynamics (RAPIDD) program. icddr,b is thankful to
the Governments of Australia, Bangladesh, Canada, Sweden and the UK for
providing core support. JRCP and ESG are supported by the Research and
Policy on Infectious Disease Dynamics (RAPIDD) Program of the Fogarty
International Center, National Institutes of Health and Science and
Technology Directorate, Department of Homeland Security. The funders had
no role in study design, data collection and analysis, decision to
publish, or preparation of the manuscript.
NR 41
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Z9 3
U1 0
U2 3
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 DEC
PY 2015
VL 9
IS 12
AR e0004074
DI 10.1371/journal.pntd.0004074
PG 7
WC Infectious Diseases; Parasitology; Tropical Medicine
SC Infectious Diseases; Parasitology; Tropical Medicine
GA DB2NG
UT WOS:000368345100003
PM 26657648
ER
PT J
AU Pajuelo, MJ
Eguiluz, M
Dahlstrom, E
Requena, D
Guzman, F
Ramirez, M
Sheen, P
Frace, M
Sammons, S
Cama, V
Anzick, S
Bruno, D
Mahanty, S
Wilkins, P
Nash, T
Gonzalez, A
Garcia, HH
Gilman, RH
Porcella, S
Zimic, M
AF Pajuelo, Monica J.
Eguiluz, Maria
Dahlstrom, Eric
Requena, David
Guzman, Frank
Ramirez, Manuel
Sheen, Patricia
Frace, Michael
Sammons, Scott
Cama, Vitaliano
Anzick, Sarah
Bruno, Dan
Mahanty, Siddhartha
Wilkins, Patricia
Nash, Theodore
Gonzalez, Armando
Garcia, Hector H.
Gilman, Robert H.
Porcella, Steve
Zimic, Mirko
CA Cysticercosis Working Grp Peru
TI Identification and Characterization of Microsatellite Markers Derived
from the Whole Genome Analysis of Taenia solium
SO PLOS NEGLECTED TROPICAL DISEASES
LA English
DT Article
ID SIMPLE SEQUENCE REPEATS; GENETIC-VARIATION; POLYMORPHIC MICROSATELLITES;
SCHISTOSOMA-JAPONICUM; EUKARYOTIC GENOMES; CODING DNA; INFECTIONS;
CYSTICERCI; DIVERSITY; FREQUENCY
AB Background
Infections with Taenia solium are the most common cause of adult acquired seizures worldwide, and are the leading cause of epilepsy in developing countries. A better understanding of the genetic diversity of T. solium will improve parasite diagnostics and transmission pathways in endemic areas thereby facilitating the design of future control measures and interventions. Microsatellite markers are useful genome features, which enable strain typing and identification in complex pathogen genomes. Here we describe microsatellite identification and characterization in T. solium, providing information that will assist in global efforts to control this important pathogen.
Methods
For genome sequencing, T. solium cysts and proglottids were collected from Huancayo and Puno in Peru, respectively. Using next generation sequencing (NGS) and de novo assembly, we assembled two draft genomes and one hybrid genome. Microsatellite sequences were identified and 36 of them were selected for further analysis. Twenty T. solium isolates were collected from Tumbes in the northern region, and twenty from Puno in the southern region of Peru. The size-polymorphism of the selected microsatellites was determined with multi-capillary electrophoresis. We analyzed the association between microsatellite polymorphism and the geographic origin of the samples.
Results
The predicted size of the hybrid (proglottid genome combined with cyst genome) T. solium genome was 111 MB with a GC content of 42.54%. A total of 7,979 contigs (>1,000 nt) were obtained. We identified 9,129 microsatellites in the Puno-proglottid genome and 9,936 in the Huancayo-cyst genome, with 5 or more repeats, ranging from mono-to hexa-nucleotide. Seven microsatellites were polymorphic and 29 were monomorphic within the analyzed isolates. T. solium tapeworms were classified into two genetic groups that correlated with the North/South geographic origin of the parasites.
Conclusions/Significance
The availability of draft genomes for T. solium represents a significant step towards the understanding the biology of the parasite. We report here a set of T. solium polymorphic microsatellite markers that appear promising for genetic epidemiology studies.
C1 [Pajuelo, Monica J.; Eguiluz, Maria; Requena, David; Guzman, Frank; Ramirez, Manuel; Sheen, Patricia; Zimic, Mirko] Univ Peruana Cayetano Heredia, Fac Ciencias & Filosofia, Lab Bioinformat & Biol Mol, Labs Invest & Desarrollo, Lima, Peru.
[Dahlstrom, Eric; Anzick, Sarah; Bruno, Dan; Mahanty, Siddhartha; Nash, Theodore; Porcella, Steve] NIAID, Genom Unit, Res Technol Sect, Rocky Mt Labs,NIH, Hamilton, MT USA.
[Frace, Michael; Sammons, Scott] Ctr Dis Control & Prevent, Biotechnol Core, Natl Ctr Emerging & Zoonot Infect Dis, Facil Branch, Atlanta, GA USA.
[Cama, Vitaliano; Wilkins, Patricia] Ctr Dis Control & Prevent, Div Parasit Dis & Malaria, Ctr Global Hlth, Atlanta, GA USA.
[Gonzalez, Armando] Univ Nacl Mayor San Marcos, Fac Med Vet, Lima 14, Peru.
[Garcia, Hector H.] Univ Peruana Cayetano Heredia, Fac Ciencias & Filosofia, Dept Microbiol, Lima, Peru.
[Garcia, Hector H.] Inst Nacl Ciencias Neurol, Lima, Peru.
[Gilman, Robert H.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Int Hlth, Baltimore, MD USA.
RP Pajuelo, MJ (reprint author), Univ Peruana Cayetano Heredia, Fac Ciencias & Filosofia, Lab Bioinformat & Biol Mol, Labs Invest & Desarrollo, Lima, Peru.
EM Mirko.zimic@upch.pe
RI Guzman, Frank /H-1271-2014;
OI Guzman, Frank /0000-0002-5048-4213; Mahanty,
Siddhartha/0000-0003-1068-0524
FU Fogarty International Center/NIH [D43TW006581, D43TW001140]; Wellcome
Trust Senior International Research Fellowship in Public Health and
Tropical Medicine
FX This work was partially supported by the Fogarty International
Center/NIH Training Grants D43TW001140 and D43TW006581. HHG. is
supported by a Wellcome Trust Senior International Research Fellowship
in Public Health and Tropical Medicine. The funders had no role in study
design, data collection and analysis or interpretaion; in writing the
report or in the decision to submit this manuscript for publication.
NR 43
TC 0
Z9 0
U1 1
U2 9
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 DEC
PY 2015
VL 9
IS 12
AR e0004316
DI 10.1371/journal.pntd.0004316
PG 15
WC Infectious Diseases; Parasitology; Tropical Medicine
SC Infectious Diseases; Parasitology; Tropical Medicine
GA DB2NG
UT WOS:000368345100061
PM 26697878
ER
PT J
AU Fritz, R
Kohan-Ghadr, HR
Sacher, A
Bolnick, AD
Kilburn, BA
Bolnick, JM
Diamond, MP
Drewlo, S
Armant, DR
AF Fritz, Rani
Kohan-Ghadr, Hamid Reza
Sacher, Alex
Bolnick, Alan D.
Kilburn, Brian A.
Bolnick, Jay M.
Diamond, Michael P.
Drewlo, Sascha
Armant, D. Randall
TI Trophoblast retrieval and isolation from the cervix (TRIC) is unaffected
by early gestational age or maternal obesity
SO PRENATAL DIAGNOSIS
LA English
DT Article
ID NONINVASIVE PRENATAL-DIAGNOSIS; CELL-FREE DNA; TRANSCERVICAL SAMPLES;
FETAL CELLS; PREECLAMPSIA; ANEUPLOIDIES; PREGNANCY; SEQUENCES; PLASMA;
MUCUS
AB Objective The objective of this study is to evaluate whether trophoblast yield obtained by trophoblast retrieval and isolation from the cervix (TRIC) is affected by pregnancy outcome, gestational age (GA) at retrieval, maternal body mass index (BMI), parity, or maternal age.
Methods TRIC was performed on 224 ongoing pregnancies between 5 and 20 weeks of GA. Trophoblast cells were isolated from cervical cells using anti-human leukocyte antigen-G antibody coupled to magnetic nanoparticles. Purity was assessed by the percentage of isolated cells that express beta-hCG. Patient records were monitored until delivery, and pregnancy outcomes were determined. Trophoblast yield was compared with GA at time of collection, maternal BMI, parity, maternal age, and outcome of pregnancy, using linear regression.
Results There was no effect of GA, maternal BMI, parity, and maternal age on trophoblast yield. Trophoblast yield decreased significantly with early pregnancy loss compared with uncomplicated pregnancies that delivered at term. Trophoblast yield with preeclampsia or intrauterine growth restriction was decreased compared with healthy term outcomes; however, they did not reach statistical significance.
Conclusions If TRIC becomes available as a method for non-invasive prenatal testing, our data demonstrate that it is unaffected by BMI and is useful as early as 5 weeks of GA. (C) 2015 John Wiley & Sons, Ltd.
C1 [Fritz, Rani; Kohan-Ghadr, Hamid Reza; Sacher, Alex; Bolnick, Alan D.; Kilburn, Brian A.; Bolnick, Jay M.; Drewlo, Sascha; Armant, D. Randall] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, 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.
RP Armant, DR (reprint author), Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA.
EM D.Armant@Wayne.edu
OI Diamond, Michael/0000-0001-6353-4489; Armant, D.
Randall/0000-0001-5904-9325
FU Intramural Research Program of the NICHD; NIH [HD071408, HL128628]; W.
K. Kellogg Foundation; March of Dimes Foundation; Perkin Elmer, Inc.
FX This research was supported in part by the Intramural Research Program
of the NICHD, grants from the NIH (HD071408 and HL128628), the W. K.
Kellogg Foundation, the March of Dimes Foundation, and Perkin Elmer,
Inc.
NR 31
TC 2
Z9 2
U1 3
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0197-3851
EI 1097-0223
J9 PRENATAL DIAG
JI Prenat. Diagn.
PD DEC
PY 2015
VL 35
IS 12
BP 1218
EP 1222
DI 10.1002/pd.4681
PG 5
WC Genetics & Heredity; Obstetrics & Gynecology
SC Genetics & Heredity; Obstetrics & Gynecology
GA DB3VV
UT WOS:000368442000010
PM 26288006
ER
PT J
AU Barile, JP
Mitchell, SA
Thompson, WW
Zack, MM
Reeve, BB
Cella, D
Smith, AW
AF Barile, John P.
Mitchell, Sandra A.
Thompson, William W.
Zack, Matthew M.
Reeve, Bryce B.
Cella, David
Smith, Ashley Wilder
TI Patterns of Chronic Conditions and Their Associations With Behaviors and
Quality of Life, 2010
SO PREVENTING CHRONIC DISEASE
LA English
DT Article
ID MULTIPLE CHRONIC CONDITIONS; MENTAL-ILLNESS; IMPROVING HEALTH;
MULTIMORBIDITY; ADULTS; OUTCOMES; OBESITY; SYSTEM; CARE
AB Introduction Co-occurring chronic health conditions elevate the risk of poor health outcomes such as death and disability, are associated with poor quality of life, and magnify the complexities of self-management, care coordination, and treatment planning. This study assessed patterns of both singular and multiple chronic conditions, behavioral risk factors, and quality of life in a population-based sample.
Methods In a national survey, adults (n = 4,184) answered questions about the presence of 27 chronic conditions. We used latent class analysis to identify patterns of chronic conditions and to explore associations of latent class membership with sociodemographic characteristics, behavioral risk factors, and health.
Results Latent class analyses indicated 4 morbidity profiles: a healthy class (class 1), a class with predominantly physical health conditions (class 2), a class with predominantly mental health conditions (class 3), and a class with both physical and mental health conditions (class 4). Class 4 respondents reported significantly worse physical health and well-being and more days of activity limitation than those in the other latent classes. Class 4 respondents were also more likely to be obese and sedentary, and those with predominantly mental health conditions were most likely to be current smokers.
Conclusions Subgroups with distinct patterns of chronic conditions can provide direction for screening and surveillance, guideline development, and the delivery of complex care services.
C1 [Barile, John P.] Univ Hawaii Manoa, Dept Psychol, Honolulu, HI 96822 USA.
[Mitchell, Sandra A.; Smith, Ashley Wilder] NCI, Rockville, MD USA.
[Thompson, William W.; Zack, Matthew M.] Ctr Dis Control & Prevent, Atlanta, GA USA.
[Reeve, Bryce B.] Univ N Carolina, Chapel Hill, NC USA.
[Cella, David] Northwestern Univ, Chicago, IL 60611 USA.
RP Barile, JP (reprint author), Univ Hawaii Manoa, Dept Psychol, 2530 Dole St,Sakamaki C400, Honolulu, HI 96822 USA.
EM Barile@hawaii.edu
RI Barile, John/F-9456-2015
OI Barile, John/0000-0003-4098-0640
NR 31
TC 1
Z9 1
U1 1
U2 3
PU CENTERS DISEASE CONTROL
PI ATLANTA
PA 1600 CLIFTON RD, ATLANTA, GA 30333 USA
SN 1545-1151
J9 PREV CHRONIC DIS
JI Prev. Chronic Dis.
PD DEC
PY 2015
VL 12
AR 150179
DI 10.5888/pcd12.150179
PG 11
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA DB7AC
UT WOS:000368665800012
ER
PT J
AU Kaufman, AR
Land, S
Parascandola, M
Augustson, E
Backinger, CL
AF Kaufman, Annette R.
Land, Stephanie
Parascandola, Mark
Augustson, Erik
Backinger, Cathy L.
TI Tobacco use transitions in the United States: The National Longitudinal
Study of Adolescent Health
SO PREVENTIVE MEDICINE
LA English
DT Article
DE Adolescent; Tobacco; Smoking; Smokeless; Tobacco; National Longitudinal
Study of Adolescent Health
ID HIGH-SCHOOL-STUDENTS; SMOKELESS TOBACCO; CIGARETTE-SMOKING; PRODUCT USE;
POLYTOBACCO USE; RISK-FACTOR; PANEL-DATA; ADULTS; PREVALENCE; PREDICTORS
AB Objectives. The purpose of this study is to evaluate and describe transitions in cigarette and smokeless tobacco (ST) use, including dual use, prospectively from adolescence into young adulthood. Methods. The current study utilizes four waves of the National Longitudinal Study of Adolescent Health (Add Health) to examine patterns of cigarette and ST use (within 30 days of survey) over time among a cohort in the United States beginning in 7th-12th grade (1995) into young adulthood (2008-2009). Transition probabilities were estimated using Markov modeling. Results. Among the cohort (N = 20,774), 48.7% reported using cigarettes, 12.8% reported using ST, and 7.2% reported dual use (cigarettes and ST in the same wave) in at least one wave. In general, the risk for transitioning between cigarettes and ST was higher for males and those who were older. Dual users exhibited a high probability (81%) of continuing dual use over time. Conclusions. Findings suggest that adolescents who use multiple tobacco products are likely to continue such use as they move into young adulthood. When addressing tobacco use among adolescents and young adults, multiple forms of tobacco use should be considered. Published by Elsevier Inc.
C1 [Kaufman, Annette R.; Land, Stephanie; Parascandola, Mark; Augustson, Erik] NCI, Tobacco Control Res Branch, Rockville, MD 20850 USA.
[Backinger, Cathy L.] US FDA, Ctr Tobacco Prod, Silver Spring, MD USA.
RP Kaufman, AR (reprint author), NCI, Tobacco Control Res Branch, Behav Res Program, Div Canc Control & Populat Sci,NIH, 9609 Med Ctr Dr,3-E-546, Rockville, MD 20850 USA.
EM kaufmana@mail.nih.gov
FU National Cancer Institute; Eunice Kennedy Shriver National Institute of
Child Health and Human Development [P01-HD31921]
FX This work was supported by the National Cancer Institute. This research
uses data from Add Health, a program project directed by Kathleen Mullan
Harris and designed by J. Richard Udry, Peter S. Bearman, and Kathleen
Mullan Harris at the University of North Carolina at Chapel Hill, and
funded by grant P01-HD31921 from the Eunice Kennedy Shriver National
Institute of Child Health and Human Development, with cooperative
funding from 23 other federal agencies and foundations. Special
acknowledgment is due Ronald R. Rindfuss and Barbara Entwisle for
assistance in the original design. Information on how to obtain the Add
Health data files is available on the Add Health website
(http://www.cpc.unc.edu/addhealth). No direct support was received from
grant P01-HD31921 for this analysis.
NR 45
TC 2
Z9 2
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 0091-7435
EI 1096-0260
J9 PREV MED
JI Prev. Med.
PD DEC
PY 2015
VL 81
BP 251
EP 257
DI 10.1016/j.ypmed.2015.08.026
PG 7
WC Public, Environmental & Occupational Health; Medicine, General &
Internal
SC Public, Environmental & Occupational Health; General & Internal Medicine
GA DB3OP
UT WOS:000368421300038
PM 26361752
ER
PT J
AU Bellatorre, A
Choi, K
Bernat, D
AF Bellatorre, Anna
Choi, Kelvin
Bernat, Debra
TI The influence of the social environment on youth smoking status
SO PREVENTIVE MEDICINE
LA English
DT Article
DE Tobacco; Adolescent health; Peer influence
ID ADOLESCENT CIGARETTE-SMOKING; PEER INFLUENCE; PREDICTORS; INITIATION;
IMPLICIT; BEHAVIOR; FRIENDS; ONSET
AB Objective. Youth smoking is complex with multilevel influences. While much is known about certain levels of influence on youth smoking, the lack of focus on institutional influences is notable. This study evaluated the effects of ambient smoking attitudes and behaviors in schools on individual youth smoking.
Method. Data from the 2012 Florida Youth Tobacco Survey (n=67,460) were analyzed. Multinomial logistic regression was used to investigate individual and aggregated school-level factors that were associated with a youth being classified as a "susceptible nonsmoker" (SN) or " current smoker" (CS) relative to a " non-susceptible nonsmoker" (NN).
Results. The aggregated percentage of regular smokers at a school, ambient school level positive smoking perceptions, and the standardized difference between individual and school-level positive smoking perceptions were statistically significant in the fully adjusted model. We also found an increased risk of being a SN relative to a NN for Hispanic youth. Moreover, our approach to modeling institutional-level factors raised the pseudo r-squared from 0.05 to 0.14.
Conclusion. These findings suggest the importance of ambient smoking attitudes and behaviors on youth smoking. Prevention efforts affecting ambient smoking attitudes may be beneficial. Published by Elsevier Inc.
C1 [Bellatorre, Anna; Choi, Kelvin] Natl Inst Minor Hlth & Hlth Dispar, Bethesda, MD 20892 USA.
[Bernat, Debra] Univ Maryland, College Pk, MD 20742 USA.
RP Choi, K (reprint author), Natl Inst Minor Hlth & Hlth Dispar, Bethesda, MD 20892 USA.
EM Kelvin.choi@nih.gov
FU Division of Intramural Research, National Institute on Minority Health
and Health Disparities, National Institutes of Health; National Cancer
Institute [R03 CA168411]
FX Dr. Bellatorre and Dr. Choi's effort on the study is funded by the
Division of Intramural Research, National Institute on Minority Health
and Health Disparities, National Institutes of Health. Dr. Bernat's
effort is supported with a grant from the National Cancer Institute (R03
CA168411; D. Bernat, Principal Investigator). The views presented in
this paper don't necessarily reflect the views of the Florida Department
of Health, the NIH, or the University of Maryland.
NR 31
TC 1
Z9 1
U1 1
U2 8
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0091-7435
EI 1096-0260
J9 PREV MED
JI Prev. Med.
PD DEC
PY 2015
VL 81
BP 309
EP 313
DI 10.1016/j.ypmed.2015.09.017
PG 5
WC Public, Environmental & Occupational Health; Medicine, General &
Internal
SC Public, Environmental & Occupational Health; General & Internal Medicine
GA DB3OP
UT WOS:000368421300048
PM 26449408
ER
PT J
AU Cherney, AR
Marin, JR
Brown, J
Anise, A
Krosnick, S
Henriksen, K
Lewis, RJ
Mills, AM
AF Cherney, Alan R.
Marin, Jennifer R.
Brown, Jeremy
Anise, Ayodola
Krosnick, Steven
Henriksen, Kerm
Lewis, Roger J.
Mills, Angela M.
TI Funding Research in Emergency Diagnostic Imaging: Summary of a Panel
Discussion at the 2015 Academic Emergency Medicine Consensus Conference
SO ACADEMIC EMERGENCY MEDICINE
LA English
DT Article; Proceedings Paper
CT Academic-Emergency-Medicine (AEM) Consensus Conference
CY MAY 12, 2015
CL San Diego, CA
SP Acad Emergency Med
ID HEALTH-CARE RESEARCH; AGENCY
AB As part of the 2015 Academic Emergency Medicine consensus conference "Diagnostic Imaging in the Emergency Department: A Research Agenda to Optimize Utilization," a panel of representatives from the National Institute of Health's Office of Emergency Care Research, the National Institute of Biomedical Imaging and Bioengineering, the Agency for Healthcare Research and Quality, and the Patient-Centered Outcomes Research Institute was assembled to discuss future opportunities for funding research in this particular area of interest. Representatives from these agencies and organizations discussed their missions and priorities and how they distribute funding. They also addressed questions on mechanisms for new and established researchers to secure future funding. (C) 2015 by the Society for Academic Emergency Medicine
C1 [Cherney, Alan R.] Lehigh Valley Hlth Network, Dept Emergency Med, Allentown, PA USA.
[Marin, Jennifer R.] Univ Pittsburgh, Sch Med, Dept Pediat, Pittsburgh, PA 15261 USA.
[Marin, Jennifer R.] Univ Pittsburgh, Sch Med, Dept Emergency Med, Pittsburgh, PA USA.
[Brown, Jeremy] Natl Inst Hlth Off Emergency Care Res, Bethesda, MD USA.
[Anise, Ayodola] Patient Ctr Outcomes Res Inst, Addressing Dispar Program, Washington, DC USA.
[Krosnick, Steven] Natl Inst Biomed Imaging & Bioengn, Bethesda, MD USA.
[Henriksen, Kerm] Agcy Healthcare Res & Qual, Ctr Qual Improvement & Patient Safety, Human Factors Advisor Patient Safety, Rockville, MD USA.
[Lewis, Roger J.] Harbor UCLA Med Ctr, Dept Emergency Med, Torrance, CA 90509 USA.
[Mills, Angela M.] Univ Penn, Dept Emergency Med, Perelman Sch Med, Philadelphia, PA 19104 USA.
RP Mills, AM (reprint author), Univ Penn, Dept Emergency Med, Perelman Sch Med, Philadelphia, PA 19104 USA.
EM millsa@uphs.upenn.edu
FU Agency for Healthcare Research and Quality [R13HS023498-01]; Agency for
Healthcare Research and Quality (AHRQ) [1R13HS023498-01]; National
Institute of Biomedical Imaging and Bioengineering [1 R13 EB 019813-01]
FX Dr. Marin was supported by the Agency for Healthcare Research and
Quality (R13HS023498-01); receives support as teaching faculty for 3rd
Rock Ultrasound, LLC; and has served as a consultant for Venaxis, Inc.;
Funding for this conference was made possible (in part) by grant number
1R13HS023498-01 from the Agency for Healthcare Research and Quality
(AHRQ) and grant number 1 R13 EB 019813-01 from the National Institute
of Biomedical Imaging and Bioengineering. The views expressed in written
conference materials or publications and by speakers and moderators do
not necessarily reflect the official policies of the Department of
Health and Human Services, nor does mention of trade names, commercial
practices, or organizations imply endorsement by the U.S. Government.
NR 12
TC 1
Z9 1
U1 0
U2 0
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 DEC
PY 2015
VL 22
IS 12
SI SI
BP 1400
EP 1405
DI 10.1111/acem.12825
PG 6
WC Emergency Medicine
SC Emergency Medicine
GA DA5FP
UT WOS:000367828900006
PM 26567519
ER
PT J
AU Yang, K
Lu, WJ
Jiang, Q
Yun, X
Zhao, MM
Jiang, HY
Wang, J
AF Yang, Kai
Lu, Wenju
Jiang, Qian
Yun, Xin
Zhao, Mingming
Jiang, Haiyang
Wang, Jian
TI Peroxisome Proliferator-Activated Receptor gamma-Mediated Inhibition on
Hypoxia-Triggered Store-Operated Calcium Entry A Caveolin-1-Dependent
Mechanism
SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
LA English
DT Article
DE pulmonary hypertension; peroxisome proliferator-activated receptor
gamma; caveolin-1; store-operated calcium entry; pulmonary arterial
smooth muscle cells
ID ARTERIAL SMOOTH-MUSCLE; INDUCED PULMONARY-HYPERTENSION; UP-REGULATES
CAVEOLIN-1; COLON-CANCER CELL; PPAR-GAMMA; ENDOTHELIAL-CELLS;
INDEPENDENT PATHWAYS; TRPC EXPRESSION; KNOCKOUT MICE; CA2+ CHANNELS
AB Our previous publication demonstrated that peroxisome proliferator-activated receptor gamma (PPAR gamma) inhibits the pathogenesis of chronic hypoxia (CH)-induced pulmonary hypertension by targeting store-operated calcium entry (SOCE) in rat distal pulmonary arterial smooth muscle cells (PASMCs). In this study, we aim to determine the role of a membrane scaffolding protein, caveolin-1, during the suppressive process ofPPAR gamma on SOCE. Adult (6-8 weeks) male Wistar rats (200-250 g) were exposed to CH (10% O-2) for 21 days to establish CH-induced pulmonary hypertension. Primary cultured rat distal PASMCs were applied for the molecular biological experiments. First, hypoxic exposure led to 2.5-fold and 1-fold increases of caveolin-1 protein expression in the distal pulmonary arteries and PASMCs, respectively. Second, effective knockdown of caveolin-1 significantly reduced hypoxia-induced SOCE for 58.2% and 41.5%, measured by Mn2+ quenching and extracellular Ca2+ restoration experiments, respectively. These results suggested that caveolin-1 acts as a crucial regulator of SOCE, and hypoxia-up-regulated caveolin-1 largely accounts for hypoxia-elevated SOCE in PASMCs. Then, by using a high-potency PPAR gamma agonist, GW1929, we detected that PPAR gamma activation inhibited SOCE and caveolin-1 protein for 62.5% and 59.8% under hypoxia, respectively, suggesting that caveolin-1 also acts as a key target during the suppressive process of PPAR gamma on SOCE in PASMCs. Moreover, by using effective small interfering RNAs against PPAR gamma and caveolin-1, and PPAR gamma antagonist, T0070907, we observed that PPAR gamma plays an inhibitory role on caveolin-1 protein by promoting its lysosomal degradation, without affecting the messenger RNA level. PPAR gamma inhibits SOCE, at least partially, by suppressing cellular caveolin-1 protein in PASMCs.
C1 [Yang, Kai; Lu, Wenju; Jiang, Qian; Yun, Xin; Wang, Jian] Guangzhou Med Univ, Affiliated Hosp 1, Guangzhou Inst Resp Dis, State Key Lab Resp Dis, Guangzhou, Guangdong, Peoples R China.
[Wang, Jian] Peoples Hosp Inner Mongolia, Div Pulm, Hohhot, Inner Mongolia, Peoples R China.
[Yang, Kai; Lu, Wenju; Jiang, Qian; Yun, Xin; Jiang, Haiyang; Wang, Jian] Johns Hopkins Univ, Sch Med, Div Pulm & Crit Care Med, Baltimore, MD 21224 USA.
[Zhao, Mingming] NIA, Lab Mol Biol & Immunol, Baltimore, MD 21224 USA.
RP Wang, J (reprint author), Johns Hopkins Univ, Sch Med, Div Pulm & Crit Care Med, 5501 Hopkins Bayview Circle,Room 4B30, Baltimore, MD 21224 USA.
EM jwang31@jhmi.edu
FU National Institutes of Health [R01-HL093020]; National Natural Science
Foundation of China [81173112, 81470246, 81170052, 81220108001];
Guangdong Natural Science Foundation [1035101200300000]; Guangzhou
Department of Education Yangcheng Scholarship grant [12A001S]; Guangzhou
Department of Natural Science grant [2014Y2-00167]; Guangdong Province
Universities and Colleges Pearl River Scholar Funded Scheme, China;
State Scholarship Fund; China Scholarship Council [201208440091]
FX This work was supported by National Institutes of Health grant
R01-HL093020, National Natural Science Foundation of China grants
81173112, 81470246, 81170052, and 81220108001, Guangdong Natural Science
Foundation team grant 1035101200300000, Guangzhou Department of
Education Yangcheng Scholarship grant 12A001S, Guangzhou Department of
Natural Science grant 2014Y2-00167, and Guangdong Province Universities
and Colleges Pearl River Scholar Funded Scheme 2014, China (W.L.). Also
supported by an award from the State Scholarship Fund and China
Scholarship Council grant 201208440091 (K.Y.).
NR 56
TC 6
Z9 6
U1 3
U2 7
PU AMER THORACIC SOC
PI NEW YORK
PA 25 BROADWAY, 18 FL, NEW YORK, NY 10004 USA
SN 1044-1549
EI 1535-4989
J9 AM J RESP CELL MOL
JI Am. J. Respir. Cell Mol. Biol.
PD DEC
PY 2015
VL 53
IS 6
BP 882
EP 892
DI 10.1165/rcmb.2015-0002OC
PG 11
WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System
SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System
GA DB3NW
UT WOS:000368419400014
PM 26020612
ER
PT J
AU Clement, TM
Inselman, AL
Goulding, EH
Willis, WD
Eddy, EM
AF Clement, Tracy M.
Inselman, Amy L.
Goulding, Eugenia H.
Willis, William D.
Eddy, Edward M.
TI Disrupting Cyclin Dependent Kinase 1 in Spermatocytes Causes Late
Meiotic Arrest and Infertility in Mice
SO BIOLOGY OF REPRODUCTION
LA English
DT Article
DE CDK1; cell cycle; chromosome condensation; male meiosis; meiotic arrest;
metaphase-promoting factor; okadaic acid; synaptonemal complex
ID MOUSE OOCYTE MEIOSIS; SYNAPTONEMAL COMPLEX; METAPHASE-I; GERM-CELL;
PACHYTENE SPERMATOCYTES; CROSSING-OVER; OKADAIC ACID; PROPHASE-I;
SPERMATOGENESIS; DYNAMICS
AB While cyclin dependent kinase 1 (CDK1) has a critical role in controlling resumption of meiosis in oocytes, its role has not been investigated directly in spermatocytes. Unique aspects of male meiosis led us to hypothesize that its role is different in male meiosis than in female meiosis. We generated a conditional knockout (cKO) of the Cdk1 gene in mouse spermatocytes to test this hypothesis. We found that CDK1-null spermatocytes undergo synapsis, chiasmata formation, and desynapsis as is seen in oocytes. Additionally, CDK1-null spermatocytes relocalize SYCP3 to centromeric foci, express H3pSer10, and initiate chromosome condensation. However, CDK1-null spermatocytes fail to form condensed bivalent chromosomes in prophase of meiosis I and instead are arrested at prometaphase. Thus, CDK1 has an essential role in male meiosis that is consistent with what is known about the role of CDK1 in female meiosis, where it is required for formation of condensed bivalent metaphase chromosomes and progression to the first meiotic division. We found that cKO spermatocytes formed fully condensed bivalent chromosomes in the presence of okadaic acid, suggesting that cKO chromosomes are competent to condense, although they do not do so in vivo. Additionally, arrested cKO spermatocytes exhibited irregular cell shape, irregular large nuclei, and large distinctive nucleoli. These cells persist in the seminiferous epithelium through the next seminiferous epithelial cycle with a lack of stage XII checkpoint-associated cell death. This indicates that CDK1 is required upstream of a checkpoint-associated cell death as well as meiotic metaphase progression in mouse spermatocytes.
C1 [Clement, Tracy M.; Inselman, Amy L.; Goulding, Eugenia H.; Willis, William D.; Eddy, Edward M.] NIEHS, Gamete Biol Grp, Reprod & Dev Biol Lab, NIH, Res Triangle Pk, NC 27709 USA.
RP Eddy, EM (reprint author), NIEHS, Gamete Biol Grp, Reprod & Dev Biol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
EM eddy@niehs.nih.gov
FU Intramural Research Program of the NIH, National Institute of
Environmental Health Sciences
FX This work was supported by the Intramural Research Program of the NIH,
National Institute of Environmental Health Sciences.
NR 77
TC 1
Z9 1
U1 0
U2 1
PU SOC STUDY REPRODUCTION
PI MADISON
PA 1691 MONROE ST,SUITE # 3, MADISON, WI 53711-2021 USA
SN 0006-3363
EI 1529-7268
J9 BIOL REPROD
JI Biol. Reprod.
PD DEC 1
PY 2015
VL 93
IS 6
AR 137
DI 10.1095/biolreprod.115.134940
PG 12
WC Reproductive Biology
SC Reproductive Biology
GA DA8UL
UT WOS:000368081800001
PM 26490841
ER
PT J
AU Sabourin, JA
Valdar, W
Nobel, AB
AF Sabourin, Jeremy A.
Valdar, William
Nobel, Andrew B.
TI A Permutation Approach for Selecting the Penalty Parameter in Penalized
Model Selection
SO BIOMETRICS
LA English
DT Article
DE LASSO; Penalized regression; Variable selection
ID REGRESSION SHRINKAGE; GENOME-WIDE; LASSO
AB We describe a simple, computationally efficient, permutation-based procedure for selecting the penalty parameter in LASSO-penalized regression. The procedure, permutation selection, is intended for applications where variable selection is the primary focus, and can be applied in a variety of structural settings, including that of generalized linear models. We briefly discuss connections between permutation selection and existing theory for the LASSO. In addition, we present a simulation study and an analysis of real biomedical data sets in which permutation selection is compared with selection based on the following: cross-validation (CV), the Bayesian information criterion (BIC), scaled sparse linear regression, and a selection method based on recently developed testing procedures for the LASSO.
C1 [Sabourin, Jeremy A.; Valdar, William] Univ N Carolina, Dept Genet, Chapel Hill, NC USA.
[Sabourin, Jeremy A.] NHGRI, Genometr Sect, Computat & Stat Genom Branch, NIH, Baltimore, MD USA.
[Nobel, Andrew B.] Univ N Carolina, Dept Stat & Operat Res, Chapel Hill, NC 27514 USA.
[Valdar, William; Nobel, Andrew B.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA.
[Nobel, Andrew B.] Univ N Carolina, Dept Biostat, Chapel Hill, NC USA.
RP Nobel, AB (reprint author), Univ N Carolina, Dept Stat & Operat Res, Chapel Hill, NC 27514 USA.
EM nobel@email.unc.edu
FU National Institute of General Medical Sciences of the National
Institutes of Health (NIH) [R01GM104125]; National Institute of Mental
Health of the NIH [R01MH101819]; National Science Foundation (NSF)
[DMS-1310002]; University of North Carolina Lineberger Comprehensive
Cancer Center; Division of Intramural Research at the National Human
Genome Research Institute, NIH
FX The authors would like to thank Kai Zhang and Alexandre Belloni for
helpful discussions concerning their work and the theoretical properties
of the permutation selection procedure. Research reported in this
manuscript was supported by the following: the National Institute of
General Medical Sciences of the National Institutes of Health (NIH)
under award number R01GM104125 (partial support for J. S. and W. V.);
the National Institute of Mental Health of the NIH under award number
R01MH101819 (A. N.); the National Science Foundation (NSF) under Grant
number DMS-1310002 (A. N.); the University of North Carolina Lineberger
Comprehensive Cancer Center (partial support for J. S. and W. V.); and
by the Division of Intramural Research at the National Human Genome
Research Institute, NIH (partial support for J. S.). The content is
solely the responsibility of the authors and does not necessarily
represent the official views of the NIH or NSF.
NR 22
TC 1
Z9 1
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0006-341X
EI 1541-0420
J9 BIOMETRICS
JI Biometrics
PD DEC
PY 2015
VL 71
IS 4
BP 1185
EP 1194
DI 10.1111/biom.12359
PG 10
WC Biology; Mathematical & Computational Biology; Statistics & Probability
SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational
Biology; Mathematics
GA DB0GT
UT WOS:000368187300035
PM 26243050
ER
PT J
AU Ribeiro-Gomes, FL
Romano, A
Lee, S
Roffe, E
Peters, NC
Debrabant, A
Sacks, D
AF Ribeiro-Gomes, F. L.
Romano, A.
Lee, S.
Roffe, E.
Peters, N. C.
Debrabant, A.
Sacks, D.
TI Apoptotic cell clearance of Leishmania major-infected neutrophils by
dendritic cells inhibits CD8(+) T-cell priming in vitro by Mer tyrosine
kinase-dependent signaling
SO CELL DEATH & DISEASE
LA English
DT Article
ID TOXOPLASMA-GONDII INFECTION; SAND FLIES; MACROPHAGES; ANTIGEN;
PHAGOCYTOSIS; TUBERCULOSIS; ACTIVATION; PROTEIN; DEATH; MICE
AB Neutrophils are the predominant recruited and infected cells during the early stages of Leishmania major infection in the skin, and depletion of neutrophils promotes immunity to infection transmitted by sand fly bite. In order to better understand how the acute neutrophilic response suppresses immunity, we assessed the consequences of the interaction between neutrophils recovered from the skin-inoculation site and bone marrow-derived dendritic cells (DCs) in vitro. The capture of infected, apoptotic neutrophils by the DCs completely inhibited their cross-presentation function that was dependent on engagement of the receptor tyrosine kinase Mer on the DCs. The capture of uninfected neutrophils, or neutrophils infected with Toxoplasma gondii, had only slight immunomodulatory effects. These studies define the clearance of infected, apoptotic neutrophils by DCs and Mer receptor signaling as central to the early immune evasion strategies of L. major, with relevance to other vector-borne pathogens delivered by bite to the skin.
C1 [Ribeiro-Gomes, F. L.; Romano, A.; Lee, S.; Peters, N. C.; Sacks, D.] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
[Roffe, E.] NIAID, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA.
[Debrabant, A.] US FDA, OBRR, CBER, Silver Spring, MD USA.
RP Sacks, D (reprint author), NIAID, Parasit Dis Lab, Bldg 4,Room B1-12,4 Ctr Dr,MSC 0425, Bethesda, MD 20892 USA.
EM dsacks@nih.gov
RI Roffe, Ester/H-4688-2012
FU Intramural Research Program of the National Institute of Allergy and
Infectious Diseases, National Institutes of Health
FX We thank M Grigg and V Pzsenny for provision of the T. gondii strain,
and C Rothlin and J Coligan for donation of the Mer-/- and
CD300f-/- mice, respectively. We thank Kim Beacht for
assistance with the animal studies. We thank T Moyer, C Henry, E
Stregevsky and B Hague for cell sorting and S Ganesan for technical
assistance with the confocal microscopy. This work was supported in part
by the Intramural Research Program of the National Institute of Allergy
and Infectious Diseases, National Institutes of Health.
NR 40
TC 7
Z9 7
U1 0
U2 2
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 DEC
PY 2015
VL 6
AR e2018
DI 10.1038/cddis.2015.351
PG 12
WC Cell Biology
SC Cell Biology
GA DB0BA
UT WOS:000368172400017
PM 26658192
ER
PT J
AU McShane, PJ
Glassroth, J
AF McShane, Pamela J.
Glassroth, Jeffrey
TI Pulmonary Disease Due to Nontuberculous Mycobacteria Current State and
New Insights
SO CHEST
LA English
DT Article
ID COMPLEX LUNG-DISEASE; AVIUM COMPLEX; CYSTIC-FIBROSIS; HYPERSENSITIVITY
PNEUMONITIS; CLINICAL-SIGNIFICANCE; RETROSPECTIVE COHORT;
ANTIBIOTIC-THERAPY; PROGNOSTIC-FACTORS; NEGATIVE PATIENTS; UNITED-STATES
AB Since pulmonary nontuberculous mycobacteria (PNTM) lung disease was last reviewed in CHEST in 2008, new information has emerged spanning multiple domains, including epidemiology, transmission and pathogenesis, clinical presentation, diagnosis, and treatment. The overall prevalence of PNTM is increasing, and in the United States, areas of highest prevalence are clustered in distinct geographic locations with common environmental and socioeconomic factors. Although the accepted paradigm for transmission continues to be inhalation from the environment, provocative reports suggest that person-to-person transmission may occur. A panoply of host factors have been investigated in an effort to elucidate why infection from this bacteria develops in ostensibly immunocompetent patients, and there has been clarification that immunocompetent patients exhibit different histopathology from immunocompromised patients with nontuberculous mycobacteria infection. It is now evident that Mycobacterium abscessus, an increasingly prevalent cause of PNTM lung disease, can be classified into three separate subspecies with differing genetic susceptibility or resistance to macrolides. Recent publications also raise the possibility of improved control of PNTM through enhanced adherence to current treatment guidelines as well as new approaches to treatment and even prevention. These and other recent developments and insights that may inform our approach to PNTM lung disease are reviewed and discussed.
C1 [McShane, Pamela J.] NHLBI, NIH, Bethesda, MD 20892 USA.
[Glassroth, Jeffrey] Univ Chicago, Div Biol Sci, Chicago, IL 60637 USA.
RP McShane, PJ (reprint author), NHLBI, NIH, Bldg 10,Room 6-3154, Bethesda, MD 20892 USA.
EM pamelamcshane@hotmail.com
NR 61
TC 7
Z9 7
U1 6
U2 11
PU AMER COLL CHEST PHYSICIANS
PI GLENVIEW
PA 2595 PATRIOT BLVD, GLENVIEW, IL 60026 USA
SN 0012-3692
J9 CHEST
JI Chest
PD DEC
PY 2015
VL 148
IS 6
BP 1517
EP 1527
DI 10.1378/chest.15-0458
PG 11
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA DB1NC
UT WOS:000368273900039
PM 26225805
ER
PT J
AU Xie, HH
Xie, T
Xu, JY
Shen, CS
Lai, ZJ
Xu, NS
Wang, SC
Shan, JJ
AF Xie Hui-Hui
Xie Tong
Xu Jian-Ya
Shen Cun-Si
Lai Zi-Juan
Xu Niu-Sheng
Wang Shou-Chuan
Shan Jin-Jun
TI Metabolomics Study of Aconitine and Benzoylaconine Induced Reproductive
Toxicity in BeWo Cell
SO CHINESE JOURNAL OF ANALYTICAL CHEMISTRY
LA English
DT Article
DE Aconitine; Benzoylaconine; Gas chromatography-mass spectrometry;
Metabolomics; BeWo cell; Fetal toxicity
ID METABONOMICS; METABOLISM; PLACENTA; RAT
AB An intracellular metabolomics method based on gas chromatography coupled with mass spectrometry (GC-MS) was established to explore the toxicity mechanism of aconitine and benzoylaconine. BeWo, a continuous cell lines originated from human placenta, was selected to establish in vitro placenta model. The intracellular metabolites were extracted after exposed to 5 mu g mL(-1) aconitine and benzoylaconine for 0, 6, 12, 24 and 36 h, respectively. The intracellular metabolic profiles were acquired by GC-MS. Orthogonal partial least squares discriminant analysis (OPLS-DA) score plot showed the time-dependent change of the metabolomic profiles between the control and intervention groups. After screening by variable influence on projection (VIP) value and one-way analysis of variance, and searching with NIST 2014 database, 11 metabolites were identified, including proline, glycine, threonine, glutamic acid, N-acetylglutamine, glutamine, lysine, histidine, succinic acid, glucose and galactose, which were mainly involved in the following pathways: (1) glutamine and glutamate metabolism; (2) glycine, serine and threonine metabolism; (3) alanine, aspartate and glutamate metabolism; (4) lysine degradation; (5) arginine and proline metabolism and (6) histidine metabolism. The results demonstrated that amino acid metabolism was the main metabolic pathway and responsible for the placental and fetal toxicity of aconitine and benzoylaconine.
C1 [Xie Hui-Hui; Xie Tong; Xu Jian-Ya; Shen Cun-Si; Wang Shou-Chuan; Shan Jin-Jun] Nanjing Univ Chinese Med, Inst Pediat Chinese Med, Jiangsu Key Lab Pediat Resp Dis, Nanjing 210023, Jiangsu, Peoples R China.
[Lai Zi-Juan] Univ Calif Davis, Genome Ctr, NIH, West Coast Metabol Ctr, Davis, CA 95616 USA.
[Xu Niu-Sheng] Thermo Fisher Sci, Shanghai 201206, Peoples R China.
RP Shan, JJ (reprint author), Nanjing Univ Chinese Med, Inst Pediat Chinese Med, Jiangsu Key Lab Pediat Resp Dis, Nanjing 210023, Jiangsu, Peoples R China.
EM jshan@njucm.edu.cn
FU Beijing Natural Science Foundation of China [81303299]
FX This work was supported by the Beijing Natural Science Foundation of
China (No. 81303299).
NR 18
TC 0
Z9 0
U1 6
U2 12
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0253-3820
EI 1872-2040
J9 CHINESE J ANAL CHEM
JI Chin. J. Anal. Chem.
PD DEC
PY 2015
VL 43
IS 12
BP 1808
EP 1812
DI 10.1016/S1872-2040(15)60881-7
PG 5
WC Chemistry, Analytical
SC Chemistry
GA DB0AZ
UT WOS:000368172300002
ER
PT J
AU Tuna, MM
Dogant, BA
Arduc, A
Imga, NN
Tutuncu, Y
Berker, D
Guler, S
AF Tuna, Mazhar M.
Dogant, Bercem A.
Arduc, Ayse
Imga, Narin Nasiroglu
Tutuncu, Yasemin
Berker, Dilek
Guler, Serdar
TI Impaired endothelial function in patients with mild primary
hyperparathyroidism improves after parathyroidectomy
SO CLINICAL ENDOCRINOLOGY
LA English
DT Article
ID FLOW-MEDIATED VASODILATION; BRACHIAL-ARTERY REACTIVITY; RISK-FACTORS;
CARDIOVASCULAR-DISEASE; PREDICTIVE-VALUE; AUDIT RESEARCH; HEART-DISEASE;
D DEFICIENCY; VITAMIN-D; HORMONE
AB Background Primary hyperparathyroidism (PHPT) is associated with cardiovascular morbidity; however, data on the reversibility of cardiovascular disease in mild primary hyperparathyroidism are conflicting. The aim of this study was to assess endothelial function in patients with mild PHPT before and after parathyroidectomy (Ptx).
Methods We prospectively evaluated 53 patients with mild PHPT (Group 1; 45 women, eight men; aged 52 +/- 3.1 years) and 46 healthy control subjects (Group 2; 38 women, eight men; aged 46 +/- 9.5 years). Endothelial function was measured as flow-mediated dilation (FMD) and carotid intima-media thickness (CIMT) using Doppler ultrasonography. Patients with diabetes mellitus, coronary heart disease, impaired renal function, hyperthyroidism, hypothyroidism and a history of smoking were excluded from the study. Patients were studied at baseline and 6-12 months after the first evaluation.
Results There were no differences with respect to age, gender and BMI between the two groups. Hypertension prevalence was three times higher in group 1 than in controls. % FMD was lower in group 1 than in group 2 (2.6 +/- 1.2 vs 14.8 +/- 9.6, P < 0.001). CIMT was higher in patients with PHPT than controls (0.69 +/- 0.18 vs 0.61 +/- 0.12, P = 0.045). This significance remained when hypertensive patients were excluded from the analysis. While FMD and CIMT improved significantly after Ptx, there were no differences in mild PHPT patients who followed without parathyroidectomy.
Conclusion FMD and CIMT are impaired in patients with mild PHPT compared to controls and improved significantly after a successful Ptx. Ptx improves endothelial function in patients with mild PHPT that may lead to decreased cardiovascular morbidity and mortality.
C1 [Tuna, Mazhar M.] Dicle Univ, Dept Metab, Med Fac Endocrinol, Diyarbakir, Turkey.
[Dogant, Bercem A.; Imga, Narin Nasiroglu; Berker, Dilek] Ankara Numune Training & Res Hosp, Dept Endocrinol & Metab, Ankara, Turkey.
[Arduc, Ayse] Natl Inst Hlth, Natl Inst Diabet & Digest & Kidney Dis, Diabet Endocrine & Obes Branch, Washington, DC USA.
[Tutuncu, Yasemin] Haydarpasa Numune Training & Res Hosp, Dept Endocrinol & Metab, Istanbul, Turkey.
[Guler, Serdar] Hitit Univ, Med Fac Endocrinol, Dept Metab, Corum, Turkey.
RP Tuna, MM (reprint author), Dicle Univ, Fac Med, Div Endocrinol & Metab, Diyarbakir, Turkey.
EM tunamazhar@gmail.com
NR 36
TC 3
Z9 3
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0300-0664
EI 1365-2265
J9 CLIN ENDOCRINOL
JI Clin. Endocrinol.
PD DEC
PY 2015
VL 83
IS 6
BP 951
EP 956
DI 10.1111/cen.12666
PG 6
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA DB1TX
UT WOS:000368293000028
PM 25393455
ER
PT J
AU Jee, YH
Celi, FS
Sampson, M
Sacks, DB
Remaley, AT
Kebebew, E
Baron, J
AF Jee, Youn Hee
Celi, Francesco S.
Sampson, Maureen
Sacks, David B.
Remaley, Alan T.
Kebebew, Electron
Baron, Jeffrey
TI Midkine concentrations in fine-needle aspiration of benign and malignant
thyroid nodules
SO CLINICAL ENDOCRINOLOGY
LA English
DT Article
ID ACID-RESPONSIVE GENE; MOUSE EMBRYOGENESIS; SERUM MIDKINE; EXPRESSION;
CARCINOMA; DIAGNOSIS; PLEIOTROPHIN; BIOPSY; MK; DIFFERENTIATION
AB Context The primary preoperative method for distinguishing malignant from benign thyroid nodules is fine-needle aspiration (FNA) cytology, but it is frequently inconclusive. Midkine (MDK) is a heparin-binding growth factor, which is overexpressed in papillary thyroid carcinoma (PTC).
Objective We measured MDK concentrations in FNA samples from benign and malignant thyroid nodules to explore the possibility that MDK measurement might aid in the evaluation of thyroid nodules.
Design 35 subjects underwent preoperative FNA of 45 thyroid nodules, followed by thyroidectomy, providing a histological diagnosis. FNA needle contents were first expressed for cytology, and then, the needle was washed with buffer for immunoassay. In 46 subjects without preoperative FNA samples, FNA was performed ex vivo on 62 nodules within surgically excised thyroid tissue.
Measurements MDK was measured using a high-sensitivity sandwich ELISA and normalized to thyroglobulin (Tg) concentration in the sample to adjust for tissue content in the aspirate.
Results The MDK/Tg ratio was higher in 18 PTCs than in 87 benign nodules (204 +/- 106 vs 1.2 +/- 0.3 ng/mg, mean +/- SEM, P < 0.001). Using a threshold of 10 ng/mg, the sensitivity and specificity of the MDK/Tg ratio for diagnosis of PTC were 67% and 99%, respectively. All follicular variant PTCs had a MDK/Tg ratio < 10 ng/mg.
Conclusions The findings indicate that, in FNA samples, the MDK/Tg ratio in PTC is greater than in benign thyroid nodules, raising the possibility that this approach might provide adjunctive diagnostic or prognostic information to complement existing approaches.
C1 [Jee, Youn Hee; Baron, Jeffrey] NIH, Sect Growth & Dev, Program Dev Endocrinol & Genet, Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD 20892 USA.
[Celi, Francesco S.] Virginia Commonwealth Univ, Div Endocrinol & Metab, Bethesda, MD USA.
[Sampson, Maureen; Sacks, David B.; Remaley, Alan T.] NIH, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA.
[Kebebew, Electron] NCI, Endocrine Oncol Branch, NIH, Bethesda, MD 20892 USA.
RP Baron, J (reprint author), NIH, Room 1-3330,10 Ctr Dr CRC,MSC 1103, Bethesda, MD 20892 USA.
EM jeffrey.baron@nih.gov
FU Intramural Research Programs of the Eunice Kennedy Shriver National
Institute of Child Health and Human Development (NICHD); National
Institute of Diabetes and Digestive and Kidney Diseases (NIDDK);
National Cancer Institute (NCI); Clinical Center of the National
Institutes of Health
FX This work was supported by the Intramural Research Programs of the
Eunice Kennedy Shriver National Institute of Child Health and Human
Development (NICHD), the National Institute of Diabetes and Digestive
and Kidney Diseases (NIDDK), the National Cancer Institute (NCI) and the
Clinical Center of the National Institutes of Health.
NR 31
TC 1
Z9 2
U1 1
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0300-0664
EI 1365-2265
J9 CLIN ENDOCRINOL
JI Clin. Endocrinol.
PD DEC
PY 2015
VL 83
IS 6
BP 977
EP 984
DI 10.1111/cen.12676
PG 8
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA DB1TX
UT WOS:000368293000032
PM 25411136
ER
PT J
AU Pathak, A
Stewart, DR
Faucz, FR
Xekouki, P
Bass, S
Vogt, A
Zhang, XJ
Boland, J
Yeager, M
Loud, JT
Nathanson, KL
McGlynn, KA
Stratakis, CA
Greene, MH
Mirabello, L
AF Pathak, Anand
Stewart, Douglas R.
Faucz, Fabio R.
Xekouki, Paraskevi
Bass, Sara
Vogt, Aurelie
Zhang, Xijun
Boland, Joseph
Yeager, Meredith
Loud, Jennifer T.
Nathanson, Katherine L.
McGlynn, Katherine A.
Stratakis, Constantine A.
Greene, Mark H.
Mirabello, Lisa
TI Rare inactivating PDE11A variants associated with testicular germ cell
tumors
SO ENDOCRINE-RELATED CANCER
LA English
DT Article
DE testicular cancer; PDE11A; rare variants; risk; cAMP
ID GENOME-WIDE ASSOCIATION; PHOSPHODIESTERASE 11A; SUSCEPTIBILITY LOCI;
CANCER; MUTATIONS; RISK; IDENTIFICATION; INDIVIDUALS; HYPERPLASIA;
POPULATION
AB Germline inactivating mutations of isoform 4 of phosphodiesterase (PDE) 11A (coded by the PDE11A gene) have been associated with familial adrenocortical tumors and familial testicular cancer. Testicular tissue is unique in expressing all four isoforms of PDE11A. In a prior candidate gene study of 94 familial testicular germ cell tumor (TGCT) subjects, we identified a significant association between the presence of functionally abnormal variants in PDE11A and familial TGCT risk. To validate this novel observation, we sequenced the PDE11A coding region in 259 additional TGCT patients (both familial and sporadic) and 363 controls. We identified 55 PDE11A variants: 20 missense, four splice-site, two nonsense, seven synonymous, and 22 intronic. Ten missense variants were novel; nine occurred in transcript variant 4 and one in transcript variant 3. Five rare mutations (p.F258Y, p.G291R, p.V820M, p.R545X, and p. K568R) were present only in cases and were significantly more common in cases vs controls (P=0.0037). The latter two novel variants were functionally characterized and shown to be functionally inactivating, resulting in reduced PDE activity and increased cAMP levels. In further analysis of this cohort, we focused on white participants only to minimize confounding due to population stratification. This study builds upon our prior reports implicating PDE11A variants in familial TGCT, provides the first independent validation of those findings, extends that work to sporadic testicular cancer, demonstrates that these variants are uncommonly but reproducibly associated with TGCT, and refines our understanding regarding which specific inactivating PDE11A variants are most likely to be associated with TGCT risk.
C1 [Pathak, Anand; Stewart, Douglas R.; Loud, Jennifer T.; Greene, Mark H.] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Faucz, Fabio R.; Xekouki, Paraskevi; Stratakis, Constantine A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Dev Endocrinol & Genet, Bethesda, MD USA.
[Bass, Sara; Vogt, Aurelie; Zhang, Xijun; Boland, Joseph; Yeager, Meredith] NCI, Canc Genom Res Lab, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA.
[Nathanson, Katherine L.] Univ Penn, Perelman Sch Med, Abramson Canc Ctr, Philadelphia, PA 19104 USA.
[Mirabello, Lisa] NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20850 USA.
[McGlynn, Katherine A.] NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20850 USA.
RP Mirabello, L (reprint author), NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, 9609 Med Ctr Dr,Room 6E422, Rockville, MD 20850 USA.
EM mirabellol@mail.nih.gov
FU National Cancer Institute, National Institutes of Health; Division of
Cancer Epidemiology and Genetics of the Intramural Research Program of
the National Cancer Institute
FX This project has been funded in part with funds from the National Cancer
Institute, National Institutes of Health. This work was supported by the
Division of Cancer Epidemiology and Genetics of the Intramural Research
Program of the National Cancer Institute (A Pathak, D R Stewart, S Bass,
AVogt, MYeager, J T Loud, K A McGlynn, MH Greene, and LMirabello) and
the Intramural Research Program of the Eunice Kennedy Shriver National
Institute of Child Health and Human Development of the National
Institute of Health (F R Faucz, P Xekouki, C A Stratakis).
NR 34
TC 1
Z9 1
U1 1
U2 4
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 DEC
PY 2015
VL 22
IS 6
BP 909
EP 917
DI 10.1530/ERC-15-0034
PG 9
WC Oncology; Endocrinology & Metabolism
SC Oncology; Endocrinology & Metabolism
GA DB0XB
UT WOS:000368230300016
PM 26459559
ER
PT J
AU Gharwan, H
Bunch, KP
Annunziata, CM
AF Gharwan, Helen
Bunch, Kristen P.
Annunziata, Christina M.
TI The role of reproductive hormones in epithelial ovarian carcinogenesis
SO ENDOCRINE-RELATED CANCER
LA English
DT Review
DE ovarian cancer; hormone action; reproductive; immune; endocrine
ID FOLLICLE-STIMULATING-HORMONE; NF-KAPPA-B; PROGESTERONE-RECEPTOR GENE;
MESSENGER-RIBONUCLEIC-ACID; GYNECOLOGIC-ONCOLOGY-GROUP;
EPIDERMAL-GROWTH-FACTOR; MULLERIAN-INHIBITING SUBSTANCE; BREAST-CANCER
CELLS; PHASE-II TRIAL; FRAGMENT-LENGTH-POLYMORPHISM
AB Epithelial ovarian cancer comprises similar to 85% of all ovarian cancer cases. Despite acceptance regarding the influence of reproductive hormones on ovarian cancer risk and considerable advances in the understanding of epithelial ovarian carcinogenesis on a molecular level, complete understanding of the biologic processes underlying malignant transformation of ovarian surface epithelium is lacking. Various hypotheses have been proposed over the past several decades to explain the etiology of the disease. The role of reproductive hormones in epithelial ovarian carcinogenesis remains a key topic of research. Primary questions in the field of ovarian cancer biology center on its developmental cell of origin, the positive and negative effects of each class of hormones on ovarian cancer initiation and progression, and the role of the immune system in the ovarian cancer microenvironment. The development of the female reproductive tract is dictated by the hormonal milieu during embryogenesis. Intensive research efforts have revealed that ovarian cancer is a heterogenous disease that may develop from multiple extra-ovarian tissues, including both Mullerian (fallopian tubes, endometrium) and non-Mullerian structures (gastrointestinal tissue), contributing to its heterogeneity and distinct histologic subtypes. The mechanism underlying ovarian localization, however, remains unclear. Here, we discuss the role of reproductive hormones in influencing the immune system and tipping the balance against or in favor of developing ovarian cancer. We comment on animal models that are critical for experimentally validating existing hypotheses in key areas of endocrine research and useful for preclinical drug development. Finally, we address emerging therapeutic trends directed against ovarian cancer.
C1 [Gharwan, Helen] NCI, NIH, Bethesda, MD 20892 USA.
[Bunch, Kristen P.; Annunziata, Christina M.] NCI, Womens Malignancies Branch, NIH, Ctr Canc Res, Bethesda, MD 20892 USA.
[Bunch, Kristen P.] Walter Reed Natl Mil Med Ctr, Dept Gynecol Oncol, Bethesda, MD USA.
RP Gharwan, H (reprint author), NCI, NIH, 10 Ctr Dr,Bldg 10, Bethesda, MD 20892 USA.
EM hgh7@hotmail.com
RI Annunziata, Christina/L-3219-2016
OI Annunziata, Christina/0000-0003-2033-6532
NR 305
TC 5
Z9 5
U1 3
U2 13
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 DEC
PY 2015
VL 22
IS 6
BP R339
EP R363
DI 10.1530/ERC-14-0550
PG 25
WC Oncology; Endocrinology & Metabolism
SC Oncology; Endocrinology & Metabolism
GA DB0XB
UT WOS:000368230300006
PM 26373571
ER
PT J
AU Gore, AC
Chappell, VA
Fenton, SE
Flaws, JA
Nadal, A
Prins, GS
Toppari, J
Zoeller, RT
AF Gore, A. C.
Chappell, V. A.
Fenton, S. E.
Flaws, J. A.
Nadal, A.
Prins, G. S.
Toppari, J.
Zoeller, R. T.
TI Executive Summary to EDC-2: The Endocrine Society's Second Scientific
Statement on Endocrine-Disrupting Chemicals
SO ENDOCRINE REVIEWS
LA English
DT Review
ID XENOESTROGENS
AB This Executive Summary to the Endocrine Society's second Scientific Statement on environmental endocrine-disrupting chemicals (EDCs) provides a synthesis of the key points of the complete statement. The full Scientific Statement represents a comprehensive review of the literature on seven topics for which there is strong mechanistic, experimental, animal, and epidemiological evidence for endocrine disruption, namely: obesity and diabetes, female reproduction, male reproduction, hormone-sensitive cancers in females, prostate cancer, thyroid, and neurodevelopment and neuroendocrine systems. EDCs such as bisphenol A, phthalates, pesticides, persistent organic pollutants such as polychlorinated biphenyls, polybrominated diethyl ethers, and dioxins were emphasized because these chemicals had the greatest depth and breadth of available information. The Statement also included thorough coverage of studies of developmental exposures to EDCs, especially in the fetus and infant, because these are critical life stages during which perturbations of hormones can increase the probability of a disease or dysfunction later in life. A conclusion of the Statement is that publications over the past 5 years have led to a much fuller understanding of the endocrine principles by which EDCs act, including nonmonotonic dose-responses, low-dose effects, and developmental vulnerability. These findings will prove useful to researchers, physicians, and other healthcare providers in translating the science of endocrine disruption to improved public health. (Endocrine Reviews 36: 593-602, 2015)
C1 [Gore, A. C.] Univ Texas Austin, Coll Pharm, Pharmacol & Toxicol, Austin, TX 78734 USA.
[Chappell, V. A.; Fenton, S. E.] NIEHS, Div Natl Toxicol Program, NIH, Res Triangle Pk, NC 27709 USA.
[Flaws, J. A.] Univ Illinois, Dept Comparat Biosci, Urbana, IL 61802 USA.
[Nadal, A.] Miguel Hernandez Univ Elche, Inst Bioengn, Alicante 03202, Spain.
[Nadal, A.] Miguel Hernandez Univ Elche, CIBERDEM, Alicante 03202, Spain.
[Prins, G. S.] Univ Illinois, Coll Med, Dept Urol, Chicago, IL 60612 USA.
[Prins, G. S.] Univ Illinois, Coll Med, Dept Pathol, Chicago, IL 60612 USA.
[Prins, G. S.] Univ Illinois, Coll Med, Dept Physiol & Biophys, Chicago, IL 60612 USA.
[Toppari, J.] Univ Turku, Dept Physiol, FIN-20520 Turku, Finland.
[Toppari, J.] Univ Turku, Dept Pediat, FIN-20520 Turku, Finland.
Turku Univ Hosp, FIN-20520 Turku, Finland.
[Zoeller, R. T.] Univ Massachusetts, Dept Biol, Amherst, MA 01003 USA.
RP Gore, AC (reprint author), Univ Texas Austin, 107 W Dean Keeton,C0875, Austin, TX 78712 USA.
EM andrea.gore@austin.utexas.edu
RI Nadal, Angel/G-6721-2014
OI Nadal, Angel/0000-0003-4178-2152
FU National Institutes of Health (NIH) [ES023254, ES020662]; NIH [ES019178,
ES02207, ES020886, CA172220, ES010026, ES020908]; Ministerio de Economia
y Competitividad [BFU2011-28358, SAF2014-58335-P]; Generalitat
Valenciana [PROMETEO/2011/080, PROMETEO/2015/016]; Academy of Finland;
EU FP7 Environment and Quality of Life; Sigrid Juselius Foundation;
Turku University Hospital Special Research Fund
FX Grant support to authors included: National Institutes of Health (NIH)
ES023254 and ES020662 (to A.C.G.); NIH ES019178 (to J.A.F.); Ministerio
de Economia y Competitividad BFU2011-28358 and SAF2014-58335-P,
Generalitat Valenciana PROMETEO/2011/080, and PROMETEO/2015/016 (to
A.N.); NIH ES02207, ES020886, and CA172220 (to G.S.P.); Academy of
Finland, EU FP7 Environment and Quality of Life, Sigrid Juselius
Foundation, and Turku University Hospital Special Research Fund (to
J.T.); and NIH ES010026, ES020908 (to R.T.Z.).
NR 7
TC 27
Z9 27
U1 2
U2 26
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD DEC
PY 2015
VL 36
IS 6
BP 593
EP 602
DI 10.1210/er.2015-1093
PG 10
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA DB1OL
UT WOS:000368277700002
PM 26414233
ER
PT J
AU Gore, AC
Chappell, VA
Fenton, SE
Flaws, JA
Nadal, A
Prins, GS
Toppari, J
Zoeller, RT
AF Gore, A. C.
Chappell, V. A.
Fenton, S. E.
Flaws, J. A.
Nadal, A.
Prins, G. S.
Toppari, J.
Zoeller, R. T.
TI EDC-2: The Endocrine Society's Second Scientific Statement on
Endocrine-Disrupting Chemicals
SO ENDOCRINE REVIEWS
LA English
DT Review
ID BISPHENOL-A EXPOSURE; IN-UTERO EXPOSURE; POLYBROMINATED DIPHENYL ETHERS;
ESTROGEN-RECEPTOR-ALPHA; ARYL-HYDROCARBON RECEPTOR; SPRAGUE-DAWLEY RATS;
PERSISTENT ORGANIC POLLUTANTS; MAMMARY-GLAND DEVELOPMENT; OVARIAN ANTRAL
FOLLICLES; EPIGENETIC TRANSGENERATIONAL INHERITANCE
AB The Endocrine Society's first Scientific Statement in 2009 provided a wake-up call to the scientific community about how environmental endocrine-disrupting chemicals (EDCs) affect health and disease. Five years later, a substantially larger body of literature has solidified our understanding of plausible mechanisms underlying EDC actions and how exposures in animals and humans-especially during development-may lay the foundations for disease later in life. At this point in history, we have much stronger knowledge about how EDCs alter gene-environment interactions via physiological, cellular, molecular, andepigenetic changes, thereby producing effects in exposed individuals as well as their descendants. Causal links between exposure and manifestation of disease are substantiated by experimental animal models and are consistent with correlative epidemiological data in humans. There are several caveats because differences in how experimental animal work is conducted can lead to difficulties in drawing broad conclusions, and we must continue to be cautious about inferring causality in humans. In this second Scientific Statement, we reviewed the literature on a subset of topics for which the translational evidence is strongest: 1) obesity and diabetes; 2) female reproduction; 3) male reproduction; 4) hormone-sensitive cancers in females; 5) prostate; 6) thyroid; and 7) neurodevelopment and neuroendocrine systems. Our inclusion criteria for studies were those conducted predominantly in the past 5 years deemed to be of high quality based on appropriate negative and positive control groups or populations, adequate sample size and experimental design, and mammalian animal studies with exposure levels in arange that was relevant to humans. We also focused on studies using the developmental origins of health and disease model. No report was excluded based on a positive or negative effect of the EDC exposure. The bulk of the results across the board strengthen the evidence for endocrine health-related actions of EDCs. Based on this much more complete understanding of the endocrine principles by which EDCs act, including nonmonotonic dose-responses, low-dose effects, and developmental vulnerability, these findings can be much better translated to human health. Armed with this information, researchers, physicians, and other healthcare providers can guide regulators and policymakers as they make responsible decisions. (Endocrine Reviews 36: E1-E150, 2015)
C1 [Gore, A. C.] Univ Texas Austin, Coll Pharm, Pharmacol & Toxicol, Austin, TX 78734 USA.
[Chappell, V. A.; Fenton, S. E.] NIEHS, Div Natl Toxicol Program, NIH, Res Triangle Pk, NC 27709 USA.
[Flaws, J. A.] Univ Illinois, Dept Comparat Biosci, Urbana, IL 61802 USA.
[Nadal, A.] Miguel Hernandez Univ Elche, Inst Bioengn, Alicante 03202, Spain.
[Nadal, A.] Miguel Hernandez Univ Elche, CIBERDEM, Alicante 03202, Spain.
[Prins, G. S.] Univ Illinois, Coll Med, Dept Urol, Chicago, IL 60612 USA.
[Prins, G. S.] Univ Illinois, Coll Med, Dept Pathol, Chicago, IL 60612 USA.
[Prins, G. S.] Univ Illinois, Coll Med, Dept Physiol & Biophys, Chicago, IL 60612 USA.
[Toppari, J.] Univ Turku, Dept Physiol, FIN-20520 Turku, Finland.
[Toppari, J.] Univ Turku, Dept Pediat, FIN-20520 Turku, Finland.
Turku Univ Hosp, FIN-20520 Turku, Finland.
[Zoeller, R. T.] Univ Massachusetts, Dept Biol, Amherst, MA 01003 USA.
RP Gore, AC (reprint author), Univ Texas Austin, 107 West Dean Keeton St,C0875, Austin, TX 78712 USA.
EM andrea.gore@austin.utexas.edu
RI Nadal, Angel/G-6721-2014
OI Nadal, Angel/0000-0003-4178-2152
FU National Institutes of Health (NIH) [ES023254, ES020662, ES019178];
Ministerio de Economia y Competitividad [BFU2011-28358,
SAF2014-58335-P]; Generalitat Valenciana [PROMETEO/2011/080,
PROMETEO/2015/016]; NIH [ES02207, ES020886, CA172220, ES010026,
ES020908]; Academy of Finland; EU FP7 Environment and Quality of Life;
Sigrid Juselius Foundation; Turku University Hospital Special Research
Fund
FX This work was supported by National Institutes of Health (NIH) Grants
ES023254 and ES020662 (to A.C.G.) and ES019178 (to J.A.F.); Ministerio
de Economia y Competitividad Grants BFU2011-28358 and SAF2014-58335-P
(to A.N.); Generalitat Valenciana Grants PROMETEO/2011/080 and
PROMETEO/2015/016 (to A.N.); NIH Grants ES02207, ES020886, and CA172220
(to G.S.P.); the Academy of Finland, EU FP7 Environment and Quality of
Life, the Sigrid Juselius Foundation, and Turku University Hospital
Special Research Fund (to J.T.); and NIH Grants ES010026 and ES020908
(to R.T.Z.).
NR 1290
TC 68
Z9 68
U1 31
U2 74
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0163-769X
EI 1945-7189
J9 ENDOCR REV
JI Endocr. Rev.
PD DEC
PY 2015
VL 36
IS 6
BP E1
EP E150
DI 10.1210/er.2015-1010
PG 150
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA DB1OL
UT WOS:000368277700001
PM 26544531
ER
PT J
AU Nicolaides, NC
Lamprokostopoulou, A
Polyzos, A
Kino, T
Katsantoni, E
Triantafyllou, P
Christophoridis, A
Katzos, G
Dracopoulou, M
Sertedaki, A
Chrousos, GP
Charmandari, E
AF Nicolaides, Nicolas C.
Lamprokostopoulou, Agaristi
Polyzos, Alexandros
Kino, Tomoshige
Katsantoni, Eleni
Triantafyllou, Panagiota
Christophoridis, Athanasios
Katzos, George
Dracopoulou, Maria
Sertedaki, Amalia
Chrousos, George P.
Charmandari, Evangelia
TI Transient generalized glucocorticoid hypersensitivity
SO EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Article
DE Glucocorticoid hypersensitivity; glucocorticoid receptor; glucocorticoid
signalling; glucocorticoids; transcriptomics
ID CORTISOL HYPERREACTIVE SYNDROME; GENE-EXPRESSION; RECEPTOR GENE;
RNA-SEQ; RESISTANCE; TRANSCRIPTS; DISORDERS; PATIENT; SYSTEMS
AB Background Transient generalized glucocorticoid hypersensitivity is a rare disorder characterized by increased tissue sensitivity to glucocorticoids and compensatory hypo-activation of the hypothalamic-pituitary-adrenal axis. The condition itself and the underlying molecular mechanisms have not been elucidated.
Objective To present the clinical manifestations, endocrinologic evaluation and transcriptomic profile in a patient with transient generalized glucocorticoid hypersensitivity.
Design and Results A 9-year-old girl presented with an 8-month history of clinical manifestations suggestive of Cushing syndrome. Endocrinologic evaluation revealed undetectable 08: 00 h ACTH (<1 pg/mL) and cortisol (0.025 mu g/dL) concentrations, which remained decreased throughout the 24-h period and did not respond to stimulation with ovine CRH. The disease gradually resolved spontaneously over the ensuing 3 months. Sequencing of the human glucocorticoid receptor gene revealed no mutations or polymorphisms. Western blot analysis in peripheral blood mononuclear cells revealed equal protein expression of hGR alpha of the patient in the disease and postresolution phases compared with a control subject. Transcriptomic analysis in peripheral blood mononuclear cells in the disease and postresolution phases identified 903 differentially expressed genes. Of these, 106 genes were up-regulated and 797 were down-regulated in the disease compared with the resolution phase. Bioinformatics analysis on the differentially expressed gene networks revealed Nuclear Factor-kappa B as the predominant transcription factor influencing the expression of the majority of differentially expressed genes.
Conclusions Our findings indicate that a transient postreceptor defect, or a virus-or bacterium-encoded molecule, may have enhanced glucocorticoid signal transduction, leading to transient generalized glucocorticoid hypersensitivity and hypo-activation of the HPA axis.
C1 [Nicolaides, Nicolas C.; Dracopoulou, Maria; Sertedaki, Amalia; Chrousos, George P.; Charmandari, Evangelia] Acad Athens, Aghia Sophia Childrens Hosp, Sch Med, Dept Pediat 1,Div Endocrinol Metab & Diabet, Athens 11527, Greece.
[Nicolaides, Nicolas C.; Lamprokostopoulou, Agaristi; Chrousos, George P.; Charmandari, Evangelia] Acad Athens, Biomed Res Fdn, Clin Res Ctr, Div Endocrinol & Metab, Athens 11527, Greece.
[Polyzos, Alexandros] Acad Athens, Biomed Res Fdn, Inst Mol Biol Genet & Biotechnol, Athens 11527, Greece.
[Kino, Tomoshige] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Unit Mol Hormone Act, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA.
[Katsantoni, Eleni] Acad Athens, Biomed Res Fdn, Clin Res Ctr, Div Hematol, Athens 11527, Greece.
[Triantafyllou, Panagiota; Christophoridis, Athanasios; Katzos, George] Aristotle Univ Thessaloniki, Sch Med, Dept Pediat 1, Thessaloniki, Greece.
[Chrousos, George P.] King Abdulaziz Univ, King Fahd Med Res Ctr, Saudi Diabet Study Res Grp, Jeddah 21413, Saudi Arabia.
RP Nicolaides, NC (reprint author), Acad Athens, Biomed Res Fdn, Clin Res Ctr, Div Endocrinol & Metab, 4 Soranou Efessiou St, Athens 11527, Greece.
EM nnicolaides@bioacademy.gr
RI Charmandari, Evangelia/B-6701-2011
FU European Union (European Social Fund - ESF); Greek national funds
through the Operational Program "Education and Lifelong Learning" of the
National Strategic Reference Framework (NSRF) - Research Funding
Program: THALIS -University of Athens (UOA), Athens, Greece
FX This work was supported by the European Union (European Social Fund -
ESF) and Greek national funds through the Operational Program "Education
and Lifelong Learning" of the National Strategic Reference Framework
(NSRF) - Research Funding Program: THALIS -University of Athens (UOA),
Athens, Greece.
NR 24
TC 0
Z9 0
U1 2
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0014-2972
EI 1365-2362
J9 EUR J CLIN INVEST
JI Eur. J. Clin. Invest.
PD DEC
PY 2015
VL 45
IS 12
BP 1306
EP 1315
DI 10.1111/eci.12554
PG 10
WC Medicine, General & Internal; Medicine, Research & Experimental
SC General & Internal Medicine; Research & Experimental Medicine
GA DA6QH
UT WOS:000367929600010
PM 26479047
ER
PT J
AU Hoa, NN
Akagawa, R
Yamasaki, T
Hirota, K
Sasa, K
Natsume, T
Kobayashi, J
Sakuma, T
Yamamoto, T
Komatsu, K
Kanemaki, MT
Pommier, Y
Takeda, S
Sasanuma, H
AF Nguyen Ngoc Hoa
Akagawa, Remi
Yamasaki, Tomomi
Hirota, Kouji
Sasa, Kentaro
Natsume, Toyoaki
Kobayashi, Junya
Sakuma, Tetsushi
Yamamoto, Takashi
Komatsu, Kenshi
Kanemaki, Masato T.
Pommier, Yves
Takeda, Shunichi
Sasanuma, Hiroyuki
TI Relative contribution of four nucleases, CtIP, Dna2, Exo1 and Mre11, to
the initial step of DNA double-strand break repair by homologous
recombination in both the chicken DT40 and human TK6 cell lines
SO GENES TO CELLS
LA English
DT Article
ID RECQ FAMILY HELICASES; END-RESECTION; SACCHAROMYCES-CEREVISIAE;
VERTEBRATE CELLS; ATM ACTIVATION; ENDONUCLEASE ACTIVITY; REPLICATION
STRESS; DAMAGE RESPONSE; PATHWAY CHOICE; MRX COMPLEX
AB Homologous recombination (HR) is initiated by double-strand break (DSB) resection, during which DSBs are processed by nucleases to generate 30 single-strand DNA. DSB resection is initiated by CtIP and Mre11 followed by long-range resection by Dna2 and Exo1 in Saccharomyces cerevisiae. To analyze the relative contribution of four nucleases, CtIP, Mre11, Dna2 and Exo1, to DSB resection, we disrupted genes encoding these nucleases in chicken DT40 cells. CtIP and Dna2 are required for DSB resection, whereas Exo1 is dispensable even in the absence of Dna2, which observation agrees with no developmental defect in Exo1-deficient mice. Despite the critical role of Mre11 in DSB resection in S. cerevisiae, loss of Mre11 only modestly impairs DSB resection in DT40 cells. To further test the role of CtIP and Mre11 in other species, we conditionally disrupted CtIP and MRE11 genes in the human TK6 B cell line. As with DT40 cells, CtIP contributes to DSB resection considerably more significantly than Mre11 in TK6 cells. Considering the critical role of Mre11 in HR, this study suggests that Mre11 is involved in a mechanism other than DSB resection. In summary, CtIP and Dna2 are sufficient for DSB resection to ensure efficient DSB repair by HR.
C1 [Nguyen Ngoc Hoa; Akagawa, Remi; Yamasaki, Tomomi; Hirota, Kouji; Sasa, Kentaro; Takeda, Shunichi; Sasanuma, Hiroyuki] Kyoto Univ, Grad Sch Med, Dept Radiat Genet, Sakyo Ku, Kyoto 6068501, Japan.
[Natsume, Toyoaki; Kanemaki, Masato T.] ROIS, Natl Inst Genet, Frontier Res Ctr, Mishima, Shizuoka 4118540, Japan.
[Kobayashi, Junya; Komatsu, Kenshi] Kyoto Univ, Ctr Radiat Biol, Dept Genome Repair Dynam, Sakyo Ku, Kyoto 6068501, Japan.
[Sakuma, Tetsushi; Yamamoto, Takashi] Hiroshima Univ, Grad Sch Sci, Dept Math & Life Sci, Higashihiroshima 7398526, Japan.
[Kanemaki, Masato T.] SOKENDAI, Dept Genet, Mishima, Shizuoka 4118540, Japan.
[Kanemaki, Masato T.] PREST, JST, Kawaguchi, Saitama 3320012, Japan.
[Pommier, Yves] NCI, Mol Pharmacol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Sasanuma, H (reprint author), Kyoto Univ, Grad Sch Med, Dept Radiat Genet, Sakyo Ku, Kyoto 6068501, Japan.
EM hiroysasa@rg.med.kyoto-u.ac.jp
RI Sakuma, Tetsushi/A-7615-2013
FU Ministry of Education, Science, Sport and Culture
FX We are grateful to P. Jeggo, J. Tainer, T. Paull and S. Gasser for his
constructive comments on the manuscript. We also thank A. Noguchi and A.
Kobayashi for their technical assistance and the laboratory members for
their stimulating discussion. FACS analysis and DNA sequencing were
carried out at the Medical Research Support Center, Graduate School of
Medicine, Kyoto University. This work was supported by a Grant-in-Aid
from the Ministry of Education, Science, Sport and Culture to J. K., K.
K., T. N., M. K., S. T. and H. S.
NR 67
TC 4
Z9 4
U1 2
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1356-9597
EI 1365-2443
J9 GENES CELLS
JI Genes Cells
PD DEC
PY 2015
VL 20
IS 12
BP 1059
EP 1076
DI 10.1111/gtc.12310
PG 18
WC Cell Biology; Genetics & Heredity
SC Cell Biology; Genetics & Heredity
GA DB1HH
UT WOS:000368258600009
PM 26525166
ER
PT J
AU Berl, MM
Walker, L
Modi, P
Irfanoglu, MO
Sarlls, JE
Nayak, A
Pierpaoli, C
AF Berl, Madison M.
Walker, Lindsay
Modi, Pooja
Irfanoglu, M. Okan
Sarlls, Joelle E.
Nayak, Amritha
Pierpaoli, Carlo
TI Investigation of Vibration-Induced Artifact in Clinical
Diffusion-Weighted Imaging of Pediatric Subjects
SO HUMAN BRAIN MAPPING
LA English
DT Article
DE diffusion tensor imaging; weight; position; quality; regrowth
ID MINIMALLY CONSCIOUS STATE; TRAUMATIC BRAIN-INJURY; ROBUST ESTIMATION;
QUALITY-CONTROL; LATE RECOVERY; TENSOR; MRI; RESTORE; TISSUES; IMPACT
AB It has been reported that mechanical vibrations of the magnetic resonance imaging scanner could produce spurious signal dropouts in diffusion-weighted images resulting in artifactual anisotropy in certain regions of the brain with red appearance in the Directionally Encoded Color maps. We performed a review of the frequency of this artifact across pediatric studies, noting differences by scanner manufacturer, acquisition protocol, as well as weight and position of the subject. We also evaluated the ability of automated and quantitative methods to detect this artifact. We found that the artifact may be present in over 50% of data in certain protocols and is not limited to one scanner manufacturer. While a specific scanner had the highest incidence, low body weight and positioning were also associated with appearance of the artifact for both scanner types evaluated, making children potentially more susceptible than adults. Visual inspection remains the best method for artifact identification. Software for automated detection showed very low sensitivity (10%). The artifact may present inconsistently in longitudinal studies. We discuss a published case report that has been widely cited and used as evidence to set policy about diagnostic criteria for determining vegetative state. That report attributed longitudinal changes in anisotropy to white matter plasticity without considering the possibility that the changes were caused by this artifact. Our study underscores the need to check for the presence of this artifact in clinical studies, analyzes circumstances for when it may be more likely to occur, and suggests simple strategies to identify and potentially avoid its effects. (C) 2015 Wiley Periodicals, Inc.
C1 [Berl, Madison M.] Div Pediat Neuropsychol, Washington, DC USA.
[Berl, Madison M.] Childrens Natl Hlth Syst, Childrens Res Inst, Washington, DC USA.
[Walker, Lindsay; Modi, Pooja; Irfanoglu, M. Okan; Nayak, Amritha; Pierpaoli, Carlo] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Pediat Imaging & Tissue Sci, Bethesda, MD USA.
[Irfanoglu, M. Okan; Nayak, Amritha] Henry Jackson Fdn, Bethesda, MD USA.
[Sarlls, Joelle E.] NINDS, NMRF, NIH, Bethesda, MD 20892 USA.
[Pierpaoli, Carlo] Uniformed Serv Univ Hlth Sci, Ctr Neurosci & Regenerat Med, Bethesda, MD 20814 USA.
RP Berl, MM (reprint author), Childrens Natl Hlth Syst, Div Neuropsychol, 111 Michigan Ave NW, Washington, DC 20010 USA.
EM mberl@childrensnational.org
FU National Institutes of Health; Neurological Disorders and Stroke
[K23NS065121- 01A2]; NICHD Intellectual and Developmental Disabilities
Research Center; Children's National Medical Center [P30HD040677];
Department of the Army [W81XWH-13-2-0019]
FX Contract grant sponsor: National Institutes of Health; Contract grant
sponsor: Neurological Disorders and Stroke; Contract grant number:
K23NS065121- 01A2 (to M.B.); Contract grant sponsor: NICHD Intellectual
and Developmental Disabilities Research Center and Children's National
Medical Center; Contract grant number: P30HD040677 (to M.B.); Contract
grant sponsor: Department of the Army; Contract grant number:
W81XWH-13-2-0019 (to A.N. and O.M.I.)
NR 41
TC 0
Z9 0
U1 2
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1065-9471
EI 1097-0193
J9 HUM BRAIN MAPP
JI Hum. Brain Mapp.
PD DEC
PY 2015
VL 36
IS 12
BP 4745
EP 4757
DI 10.1002/hbm.22846
PG 13
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA DB1QF
UT WOS:000368283100001
PM 26350492
ER
PT J
AU Zhu, X
Dutta, N
Helton, SG
Schwandt, M
Yan, J
Hodgkinson, CA
Cortes, CR
Kerich, M
Hall, S
Sun, H
Phillips, M
Momenan, R
Lohoff, FW
AF Zhu, Xi
Dutta, Nisha
Helton, Sarah G.
Schwandt, Melanie
Yan, Jia
Hodgkinson, Colin A.
Cortes, Carlos R.
Kerich, Mike
Hall, Samuel
Sun, Hui
Phillips, Monte
Momenan, Reza
Lohoff, Falk W.
TI Resting-State Functional Connectivity and Presynaptic Monoamine
Signaling in Alcohol Dependence
SO HUMAN BRAIN MAPPING
LA English
DT Article
DE genetics; monoamine transporter; presynaptic; resting-state; mPFC;
SLC18A1
ID INDEPENDENT COMPONENT ANALYSIS; EXECUTIVE CONTROL NETWORK;
CENTRAL-NERVOUS-SYSTEM; 1 GENE VMAT1/SLC18A1; HUMAN BRAIN; SUBSEQUENT
RELAPSE; CHROMOSOME 8P; ASSOCIATION; ROBUST; POLYMORPHISMS
AB Alcohol Dependence (AD) is a chronic relapsing disorder with high degrees of morbidity and mortality. While multiple neurotransmitter systems are involved in the complex symptomatology of AD, monoamine dysregulation and subsequent neuroadaptations have been long postulated to play an important role. Presynaptic monoamine transporters, such as the vesicular monoamine transporter 1 (VMAT1), are likely critical as they represent a key common entry point for monoamine regulation and may represent a shared pathway for susceptibility to AD. Excessive monoaminergic signaling as mediated by genetic variation in VMAT1 might affect functional brain connectivity in particular in alcoholics compared to controls. We conducted resting-state fMRI functional connectivity (FC) analysis using the independent component analysis (ICA) approach in 68 AD subjects and 72 controls. All subjects were genotyped for the Thr136Ile (rs1390938) variant in VMAT1. Functional connectivity analyses showed a significant increase of resting-state FC in 4 networks in alcoholics compared to controls (P<0.05, corrected). The FC was significantly positively correlated with Alcohol Dependence Scale (ADS). The hyperfunction allele 136Ile was associated with a significantly decreased FC in the Default Mode Network, Prefrontal Cortex Network, and Executive Control Network in alcohol dependent participants (P<0.05, corrected), but not in controls. Our data suggest that increased FC might represent a neuroadaptive mechanism relevant to AD that is furthermore mediated by genetic variation in VMAT1. The hyperfunction allele Thr136Ile might have a protective effect that is, in particular, relevant in AD by mechanism of increased monoamine transport into presynaptic storage vesicles. Published 2015.
C1 [Zhu, Xi; Cortes, Carlos R.; Kerich, Mike; Momenan, Reza] NIAAA, Sect Brain & Electrophysiol & Imaging, NIH, Bethesda, MD USA.
[Dutta, Nisha; Helton, Sarah G.; Schwandt, Melanie; Hall, Samuel; Sun, Hui; Phillips, Monte; Lohoff, Falk W.] NIAAA, Sect Clin Genom & Expt Therapeut, NIH, Bethesda, MD USA.
[Yan, Jia] NIAAA, Sect Human Psychopharmacol, NIH, Bethesda, MD USA.
[Hodgkinson, Colin A.] NIAAA, Neurogenet Lab, NIH, Bethesda, MD USA.
RP Lohoff, FW (reprint author), NIAAA, Sect Clin Genom & Expt Therapeut CGET, Lasker Clin Res Scholar, LCTS,NIH, 10 Ctr Dr,10CRC-22352, Bethesda, MD 20892 USA.
EM falk.lohoff@nih.gov
RI Schwandt, Melanie/L-9866-2016; Lohoff, Falk/M-7951-2016
FU National Institute on Alcohol Abuse and Alcoholism
FX Contract grant sponsor: National Institute on Alcohol Abuse and
Alcoholism.
NR 53
TC 5
Z9 5
U1 4
U2 9
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1065-9471
EI 1097-0193
J9 HUM BRAIN MAPP
JI Hum. Brain Mapp.
PD DEC
PY 2015
VL 36
IS 12
BP 4808
EP 4818
DI 10.1002/hbm.22951
PG 11
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA DB1QF
UT WOS:000368283100005
PM 26368063
ER
PT J
AU Ding, XY
Yang, YH
Stein, EA
Ross, TJ
AF Ding, Xiaoyu
Yang, Yihong
Stein, Elliot A.
Ross, Thomas J.
TI Multivariate Classification of Smokers and Nonsmokers Using SVM-RFE on
Structural MRI Images
SO HUMAN BRAIN MAPPING
LA English
DT Article
DE smoking addiction; structural MRI; voxel-based morphometry; support
vector machine; recursive feature elimination; multivariate
classification
ID SUPPORT VECTOR MACHINES; VOXEL-BASED MORPHOMETRY; STATE FUNCTIONAL
CONNECTIVITY; GRAY-MATTER VOLUMES; SMOKING-CESSATION;
SCHIZOPHRENIA-PATIENTS; ANATOMICAL NETWORKS; CIGARETTE-SMOKING; HEALTHY
CONTROLS; BRAIN
AB Voxel-based morphometry (VBM) studies have revealed gray matter alterations in smokers, but this type of analysis has poor predictive value for individual cases, which limits its applicability in clinical diagnoses and treatment. A predictive model would essentially embody a complex biomarker that could be used to evaluate treatment efficacy. In this study, we applied VBM along with a multivariate classification method consisting of a support vector machine with recursive feature elimination to discriminate smokers from nonsmokers using their structural MRI data. Mean gray matter volumes in 1,024 cerebral cortical regions of interest created using a subparcellated version of the Automated Anatomical Labeling template were calculated from 60 smokers and 60 nonsmokers, and served as input features to the classification procedure. The classifier achieved the highest accuracy of 69.6% when taking the 139 highest ranked features via 10-fold cross-validation. Critically, these features were later validated on an independent testing set that consisted of 28 smokers and 28 nonsmokers, yielding a 64.04% accuracy level (binomial P = 0.01). Following classification, exploratory post hoc regression analyses were performed, which revealed that gray matter volumes in the putamen, hippocampus, prefrontal cortex, cingulate cortex, caudate, thalamus, pre-/post-central gyrus, precuneus, and the parahippocampal gyrus, were inversely related to smoking behavioral characteristics. These results not only indicate that smoking related gray matter alterations can provide predictive power for group membership, but also suggest that machine learning techniques can reveal underlying smoking-related neurobiology.
C1 [Ding, Xiaoyu; Yang, Yihong; Stein, Elliot A.; Ross, Thomas J.] NIDA, Neuroimaging Res Branch, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
RP Ross, TJ (reprint author), NIDA, Neuroimaging Res Branch, Intramural Res Program, NIH, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM tross@mail.nih.gov
FU Intramural Research Program of the National Institute on Drug Abuse and
FDA [NDA13001-001-00000]
FX Contract grant sponsor: Intramural Research Program of the National
Institute on Drug Abuse and FDA (to E.A.S.); Contract grant number:
NDA13001-001-00000.
NR 61
TC 2
Z9 2
U1 3
U2 8
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1065-9471
EI 1097-0193
J9 HUM BRAIN MAPP
JI Hum. Brain Mapp.
PD DEC
PY 2015
VL 36
IS 12
BP 4869
EP 4879
DI 10.1002/hbm.22956
PG 11
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA DB1QF
UT WOS:000368283100010
PM 26497657
ER
PT J
AU Kooragayala, K
Gotoh, N
Cogliati, T
Nellissery, J
Kaden, TR
French, S
Balaban, R
Li, W
Covian, R
Swaroop, A
AF Kooragayala, Keshav
Gotoh, Norimoto
Cogliati, Tiziana
Nellissery, Jacob
Kaden, Talia R.
French, Stephanie
Balaban, Robert
Li, Wei
Covian, Raul
Swaroop, Anand
TI Quantification of Oxygen Consumption in Retina Ex Vivo Demonstrates
Limited Reserve Capacity of Photoreceptor Mitochondria
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE oxidative stress; neurodegeneration; photoreceptor homeostasis; retinal
disease; mitochondrial function
ID OXIDATIVE STRESS; MOUSE MODELS; CELL-DEATH; DEGENERATION; ROD;
PHOSPHORYLATION; DYSFUNCTION; OUTER; NRL; NEURODEGENERATION
AB PURPOSE. Cell death in neurodegeneration occurs at the convergence of diverse metabolic pathways. In the retina, a common underlying mechanism involves mitochondrial dysfunction since photoreceptor homeostasis and survival are highly susceptible to altered aerobic energy metabolism. We sought to develop an assay to directly measure oxygen consumption in intact retina with the goal of identifying alterations in respiration during photoreceptor dysfunction and degeneration.
METHODS. Circular punches of freshly isolated mouse retina, adjacent to the optic nerve head, were used in the microplate-based Seahorse Extracellular Flux Analyzer to measure oxygen consumption. Tissue integrity was evaluated by propidium iodide staining and live imaging. Different substrates were tested for mitochondrial respiration. Basal and maximal respiration were expressed as oxygen consumption rate (OCR) and respectively measured in Ames' medium before and after the addition of mitochondrial uncoupler, BAM15.
RESULTS. We show that glucose is an essential substrate for retinal mitochondria. At baseline, mitochondria respiration in the intact wild-type retina was close to maximal, with limited reserve capacity. Similar OCR and limited mitochondrial reserve capacity was also observed in cone-only Nrl(-/-) retina. However, the retina of Pde6brd1/rd1, Cep290rd16/rd16 and Rpgrip1(-/-) mice, all with dysfunctional or no photoreceptors, had reduced OCR and higher mitochondrial reserve capacity.
CONCLUSIONS. We have optimized a method to directly measure oxygen consumption in acutely isolated, ex vivo mouse retina and demonstrate that photoreceptors have low mitochondrial reserve capacity. Our data provide a plausible explanation for the high vulnerability of photoreceptors to altered energy homeostasis caused by mutations or metabolic challenges.
C1 [Kooragayala, Keshav; Gotoh, Norimoto; Cogliati, Tiziana; Nellissery, Jacob; Swaroop, Anand] NEI, Neurobiol Neurodegenerat & Repair Lab, NIH, Bethesda, MD 20892 USA.
[Kaden, Talia R.; Li, Wei] NEI, Retinal Neurobiol Sect, NIH, Bethesda, MD 20892 USA.
[French, Stephanie; Balaban, Robert; Covian, Raul] NHLBI, Lab Cardiac Energet, NIH, Bethesda, MD 20892 USA.
RP Swaroop, A (reprint author), Bldg 6,Rm 338 MSC0610,6 Ctr Dr, Bethesda, MD 20892 USA.
EM raul.coviangarcia@nih.gov; swaroopa@nei.nih.gov
OI Swaroop, Anand/0000-0002-1975-1141
FU National Eye Institute, National Institutes of Health [EY000473,
EY000474]
FX Supported by the Intramural Research Program of the National Eye
Institute, National Institutes of Health (EY000473, EY000474). The
authors alone are responsible for the content and writing of the paper.
NR 41
TC 3
Z9 3
U1 3
U2 4
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
EI 1552-5783
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD DEC
PY 2015
VL 56
IS 13
BP 8428
EP 8436
DI 10.1167/iovs.15-17901
PG 9
WC Ophthalmology
SC Ophthalmology
GA DB1BU
UT WOS:000368243800100
PM 26747773
ER
PT J
AU Babalonis, S
Hampson, AJ
Lofwall, MR
Nuzzo, PA
Walsh, SL
AF Babalonis, Shanna
Hampson, Aidan J.
Lofwall, Michelle R.
Nuzzo, Paul A.
Walsh, Sharon L.
TI Quinine as a Potential Tracer for Medication Adherence: A
Pharmacokinetic and Pharmacodynamic Assessment of Quinine Alone and in
Combination With Oxycodone in Humans
SO JOURNAL OF CLINICAL PHARMACOLOGY
LA English
DT Article
DE adherence; tracer; quinine; oxycodone; human; pharmacokinetic
ID TONIC WATER; DRUG; PHARMACOTHERAPY; HYDROCHLORIDE; RIBOFLAVIN;
DEPENDENCE; LIABILITY; TOXICITY; HEROIN; CYP3A4
AB Effective strategies to monitor pharmacotherapy adherence are necessary, and sensitive biological markers are lacking. This study examined a subtherapeutic dose of quinine as a potential adherence tracer. Primary aims included examination of the plasma and urinary pharmacokinetic profile of once-daily quinine; secondary aims assessed pharmacokinetic/pharmacodynamic interactions with oxycodone (a CYP3A and CYP2D substrate). Healthy, nondependent opioid users (n = 9) were enrolled in this within-subject, double-blind, placebo-controlled inpatient study. Participants received the following oral doses: day 1, oxycodone (30 mg); days 2-4, quinine (80 mg); day 5, quinine and oxycodone (2 hours postquinine). Blood and 24-hour urine samples were collected throughout the study, and pharmacodynamic outcomes were assessed during experimental sessions (days 1, 4, 5). Quinine displayed a plasma T-max similar to 2 hours and t(1/2) similar to 10 hours. Oxycodone and noroxycodone parameters (T-max, C-max, t(1/2)) were similar with or without quinine present, although drug exposure (AUC) was slightly greater when combined with quinine. No pharmacodynamic interactions were detected, and doses were safely tolerated. During washout, quinine urinary concentrations steadily declined (elimination t(1/2) similar to 16 hours), with a 94% decrease observed 72 hours postdose. Overall, low-dose quinine appears to be a good candidate for a medication additive to monitor adherence for detection of missed medication.
C1 [Babalonis, Shanna; Lofwall, Michelle R.; Walsh, Sharon L.] Univ Kentucky, Coll Med, Dept Behav Sci, Lexington, KY 40508 USA.
[Babalonis, Shanna; Lofwall, Michelle R.; Nuzzo, Paul A.; Walsh, Sharon L.] Univ Kentucky, Ctr Drug & Alcohol Res, Lexington, KY 40508 USA.
[Hampson, Aidan J.] NIDA, Div Pharmacotherapies & Med Consequences, Rockville, MD USA.
[Lofwall, Michelle R.; Walsh, Sharon L.] Univ Kentucky, Coll Med, Dept Psychiat, Lexington, KY 40508 USA.
[Walsh, Sharon L.] Univ Kentucky, Coll Pharm, Dept Pharmaceut Sci, Lexington, KY 40508 USA.
[Walsh, Sharon L.] Univ Kentucky, Coll Med, Dept Pharmacol, Lexington, KY 40508 USA.
RP Babalonis, S (reprint author), Univ Kentucky, Coll Med, Dept Behav Sci, Ctr Drug & Alcohol Res, 845 Angliana Ave, Lexington, KY 40508 USA.
EM babalonis@uky.edu
FU National Institute on Drug Abuse [R01DA016718-08S1]; National Center for
Research Resources; National Center for Advancing of Translational
Sciences (UK CTSA) [UL1TR000117-04]; National Center for Advancing of
Translational Sciences [KL2TR000116-04]
FX Grants from the National Institute on Drug Abuse (R01DA016718-08S1
[SLW]) and the National Center for Research Resources and National
Center for Advancing of Translational Sciences (UL1TR000117-04 [UK
CTSA]; KL2TR000116-04 [SB]) provided support for this research. We thank
the staff at the University of Kentucky (UK) Center on Drug and Alcohol
Research for research support: Stacy Conley, RN, Victoria Vessels, Tasia
York, and John Beninato; Leta Hommel, Ken Westberry of the UK Center for
Clinical and Translational Science (CCTS) Laboratory for assistance with
specimens; the UK Investigational Pharmacy for preparing study
medication, UK CCTS Inpatient Unit nursing staff for patient care,
especially Lisa Chamblin, RN, for exceptional phlebotomy; and Dr.
Samy-Claude Elayi (UK Department of Cardiology, Gill Heart Institute)
for patient support. We also thank staff at the University of California
San Francisco Drug Studies Unit for assay development and sample
analyses: Dr. Young Huang, Winnie Gee, Shirley Yee, and Karen Kuncze;
and Dr. Nora Chiang and Dr. Philip Krieter at the National Institute on
Drug Abuse, Division of Pharmacotherapies and Medical Consequences of
Drug Abuse, Chemistry and Pharmaceuticals Branch, for pharmacokinetic
expertise and support.
NR 40
TC 3
Z9 3
U1 0
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0091-2700
EI 1552-4604
J9 J CLIN PHARMACOL
JI J. Clin. Pharmacol.
PD DEC
PY 2015
VL 55
IS 12
BP 1332
EP 1343
DI 10.1002/jcph.557
PG 12
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA DA6ZH
UT WOS:000367953900002
PM 26032168
ER
PT J
AU Petruczynik, A
Ciesla, LM
AF Petruczynik, Anna
Ciesla, Lukasz M.
TI Thin-Layer Chromatography in the Analysis of Biologically Active Ionic
and Ionizable Compounds
SO JPC-JOURNAL OF PLANAR CHROMATOGRAPHY-MODERN TLC
LA English
DT Review
DE Review; Ionic compounds; Weak electrolytes; Alkaloids; Phenolic acids
ID INDICATING HPTLC METHOD; PHARMACEUTICAL DOSAGE FORM; TLC-DENSITOMETRIC
METHOD; MULTIDIMENSIONAL PLANAR CHROMATOGRAPHY; BONDED STATIONARY
PHASES; DIODE-ARRAY DETECTION; QUANTITATIVE-ANALYSIS; HUMAN SERUM; BULK
DRUG; BIOSYNTHETIC PRECURSORS
AB Ionic and ionizable solutes constitute a large group of compounds characterized with biological activity. Chromatographic analysis of these compounds is more difficult when compared to nonionic substances. This review focuses on different approaches used for the separation of basic and acidic substances by means of thin-layer chromatography. Biologically active basic compounds are more often used as prescribed drugs; therefore, chromatographic analysis of these substances was described in more detail when compared to acidic solutes.
Direct stimulus to write this review was the 65th anniversary of Prof. Monika Waksmundzka-Hajnos' birthday. Prof. Hajnos is known for her great contributions to chromatographic analysis of ionic solutes.
C1 [Petruczynik, Anna; Ciesla, Lukasz M.] Med Univ Lublin, Dept Inorgan Chem, PL-20093 Lublin, Poland.
[Ciesla, Lukasz M.] NIA, Lab Clin Invest, NIH, Baltimore, MD 21224 USA.
RP Petruczynik, A (reprint author), Med Univ Lublin, Dept Inorgan Chem, Chodzki 4a, PL-20093 Lublin, Poland.
EM anna.petruczynik@onet.pl; lukasz.ciesla@umlub.pl
NR 99
TC 1
Z9 1
U1 4
U2 12
PU AKADEMIAI KIADO RT
PI BUDAPEST
PA PRIELLE K U 19, PO BOX 245,, H-1117 BUDAPEST, HUNGARY
SN 0933-4173
EI 1789-0993
J9 JPC-J PLANAR CHROMAT
JI JPC-J. Planar Chromatogr.-Mod. TLC
PD DEC
PY 2015
VL 28
IS 6
BP 413
EP 425
DI 10.1556/1006.2015.28.6.1
PG 13
WC Chemistry, Analytical
SC Chemistry
GA DB0VU
UT WOS:000368226400001
ER
PT J
AU Miller, FG
Kim, SYH
AF Miller, Franklin G.
Kim, Scott Y. H.
TI Personal Care in Learning Health Care Systems
SO KENNEDY INSTITUTE OF ETHICS JOURNAL
LA English
DT Article
ID MAMMARY-ARTERY LIGATION; INFORMED-CONSENT; CONTROLLED-TRIALS;
DISTINCTION; ETHICS
AB The idea of a "learning health care system" one that systematically integrates clinical research with medical care has received considerable attention recently. Some commentators argue that under certain conditions pragmatic comparative effectiveness randomized trials can be conducted ethically within the context of a learning health care system without the informed consent of patients for research participation. In this article, we challenge this perspective and contend that conducting randomized trials of individual treatment options without consent is neither necessary nor desirable to promote and sustain learning health care systems. Our argument draws on the normative conception of personal care developed by Charles Fried in a landmark 1974 book on the ethics of randomized controlled trials.
C1 [Miller, Franklin G.] Weill Cornell Med Coll, Med Eth Med, New York, NY 10065 USA.
[Miller, Franklin G.] Hastings Ctr, New York, NY USA.
[Kim, Scott Y. H.] NIH, Dept Bioeth, Bethesda, MD USA.
[Kim, Scott Y. H.] Univ Michigan, Psychiat, Ann Arbor, MI 48109 USA.
[Kim, Scott Y. H.] Univ Michigan, Ctr Bioeth & Behav Sci Med, Ann Arbor, MI 48109 USA.
RP Miller, FG (reprint author), Weill Cornell Med Coll, Med Eth Med, New York, NY 10065 USA.
FU Intramural Research Program of the Clinical Center, NIH
FX This research was supported by the Intramural Research Program of the
Clinical Center, NIH.
NR 19
TC 0
Z9 0
U1 1
U2 2
PU JOHNS HOPKINS UNIV PRESS
PI BALTIMORE
PA JOURNALS PUBLISHING DIVISION, 2715 NORTH CHARLES ST, BALTIMORE, MD
21218-4363 USA
SN 1054-6863
EI 1086-3249
J9 KENNEDY INST ETHIC J
JI Kennedy Inst. Ethics J.
PD DEC
PY 2015
VL 25
IS 4
BP 419
EP 435
PG 17
WC Ethics; Philosophy; Social Issues
SC Social Sciences - Other Topics; Philosophy; Social Issues
GA DB2BV
UT WOS:000368314200005
PM 26775880
ER
PT J
AU Capala, J
Goetsch, SJ
Orton, CG
AF Capala, Jacek
Goetsch, Steven J.
Orton, Colin G.
TI Medical use of all high activity sources should be eliminated for
security concerns
SO MEDICAL PHYSICS
LA English
DT Editorial Material
C1 [Capala, Jacek] NCI, Div Canc Treatment & Diag, Bethesda, MD 20852 USA.
[Goetsch, Steven J.] San Diego Gamma Knife Ctr, La Jolla, CA 92037 USA.
RP Capala, J (reprint author), NCI, Div Canc Treatment & Diag, Bethesda, MD 20852 USA.
EM capalaj@mail.nih.gov; stevegoetsch@sdgkc.com
NR 18
TC 0
Z9 0
U1 0
U2 4
PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS
PI MELVILLE
PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA
SN 0094-2405
EI 2473-4209
J9 MED PHYS
JI Med. Phys.
PD DEC
PY 2015
VL 42
IS 12
BP 6773
EP 6775
DI 10.1118/1.4934823
PG 3
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA DB1BX
UT WOS:000368244100001
PM 26632034
ER
PT J
AU Forest, A
Amatulli, M
Ludwig, DL
Damoci, CB
Wang, Y
Burns, CA
Donoho, GP
Zanella, N
Fiebig, HH
Prewett, MC
Surguladze, D
DeLigio, JT
Houghton, PJ
Smith, MA
Novosiadly, R
AF Forest, Amelie
Amatulli, Michael
Ludwig, Dale L.
Damoci, Christopher B.
Wang, Ying
Burns, Colleen A.
Donoho, Gregory P.
Zanella, Nina
Fiebig, Heinz H.
Prewett, Marie C.
Surguladze, David
DeLigio, James T.
Houghton, Peter J.
Smith, Malcolm A.
Novosiadly, Ruslan
TI Intrinsic Resistance to Cixutumumab Is Conferred by Distinct Isoforms of
the Insulin Receptor
SO MOLECULAR CANCER RESEARCH
LA English
DT Article
ID GROWTH-FACTOR-I; ADVANCED SOLID TUMORS; MONOCLONAL-ANTIBODY; PHASE-2
TRIAL; KINASE INHIBITORS; COLORECTAL-CANCER; TARGETED THERAPY;
EWINGS-SARCOMA; LUNG-CANCER; OPEN-LABEL
AB Despite a recent shift away from anti-insulin-like growth factor I receptor (IGF-IR) therapy, this target has been identified as a key player in the resistance mechanisms to various conventional and targeted agents, emphasizing its value as a therapy, provided that it is used in the right patient population. Molecular markers predictive of antitumor activity of IGF-IR inhibitors remain largely unidentified. The aim of this study is to evaluate the impact of insulin receptor (IR) isoforms on the antitumor efficacy of cixutumumab, a humanized mAb against IGF-IR, and to correlate their expression with therapeutic outcome. The data demonstrate that expression of total IR rather than individual IR isoforms inversely correlates with single-agent cixutumumab efficacy in pediatric solid tumor models in vivo. Total IR, IR-A, and IR-B expression adversely affects the outcome of cixutumumab in combination with chemotherapy in patient-derived xenograft models of lung adenocarcinoma. IR-A overexpression in tumor cells confers complete resistance to cixutumumab in vitro and in vivo, whereas IR-B results in a partial resistance. Resistance in IR-B-overexpressing cells is fully reversed by anti-IGF-II antibodies, suggesting that IGF-II is a driver of cixutumumab resistance in this setting. The present study links IR isoforms, IGF-II, and cixutumumab efficacy mechanistically and identifies total IR as a biomarker predictive of intrinsic resistance to anti-IGF-IR antibody.
C1 [Forest, Amelie; Amatulli, Michael; Ludwig, Dale L.; Damoci, Christopher B.; Wang, Ying; Burns, Colleen A.; Prewett, Marie C.; Surguladze, David; DeLigio, James T.; Novosiadly, Ruslan] Eli Lilly & Co, New York, NY 10016 USA.
[Donoho, Gregory P.] Eli Lilly & Co, Indianapolis, IN 46285 USA.
[Zanella, Nina; Fiebig, Heinz H.] Oncotest, Freiburg, Germany.
[Houghton, Peter J.] Nationwide Childrens Hosp, Columbus, OH USA.
[Smith, Malcolm A.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
RP Novosiadly, R (reprint author), Eli Lilly & Co, 450 East 29th St,11th Floor, New York, NY 10016 USA.
EM ruslan.novosiadly@lilly.com
FU NCI [NO1-CM-42216, CA165995]
FX This work was funded in part by the NCI grants (NO1-CM-42216 and
CA165995).
NR 49
TC 1
Z9 1
U1 0
U2 1
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1541-7786
EI 1557-3125
J9 MOL CANCER RES
JI Mol. Cancer Res.
PD DEC
PY 2015
VL 13
IS 12
BP 1615
EP 1626
DI 10.1158/1541-7786.MCR-15-0279
PG 12
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA DB3UD
UT WOS:000368436500009
PM 26263910
ER
PT J
AU Drummond, RA
Collar, AL
Swamydas, M
Rodriguez, CA
Lim, JK
Mendez, LM
Fink, DL
Hsu, AP
Zhai, B
Karauzum, H
Mikelis, CM
Rose, SR
Ferre, EMN
Yockey, L
Lemberg, K
Kuehn, HS
Rosenzweig, SD
Lin, X
Chittiboina, P
Datta, SK
Belhorn, TH
Weimer, ET
Hernandez, ML
Hohl, TM
Kuhns, DB
Lionakis, MS
AF Drummond, Rebecca A.
Collar, Amanda L.
Swamydas, Muthulekha
Rodriguez, Carlos A.
Lim, Jean K.
Mendez, Laura M.
Fink, Danielle L.
Hsu, Amy P.
Zhai, Bing
Karauzum, Hatice
Mikelis, Constantinos M.
Rose, Stacey R.
Ferre, Elise M. N.
Yockey, Lynne
Lemberg, Kimberly
Kuehn, Hye Sun
Rosenzweig, Sergio D.
Lin, Xin
Chittiboina, Prashant
Datta, Sandip K.
Belhorn, Thomas H.
Weimer, Eric T.
Hernandez, Michelle L.
Hohl, Tobias M.
Kuhns, Douglas B.
Lionakis, Michail S.
TI CARD9-Dependent Neutrophil Recruitment Protects against Fungal Invasion
of the Central Nervous System
SO PLOS PATHOGENS
LA English
DT Article
ID INHERITED CARD9 DEFICIENCY; ANTIFUNGAL IMMUNITY; CEREBROSPINAL-FLUID;
CHEMOKINE RECEPTORS; MENINGITIS; MENINGOENCEPHALITIS; CANDIDIASIS;
INFECTIONS; MUTATIONS; CHILDREN
AB Candida is the most common human fungal pathogen and causes systemic infections that require neutrophils for effective host defense. Humans deficient in the C-type lectin pathway adaptor protein CARD9 develop spontaneous fungal disease that targets the central nervous system (CNS). However, how CARD9 promotes protective antifungal immunity in the CNS remains unclear. Here, we show that a patient with CARD9 deficiency had impaired neutrophil accumulation and induction of neutrophil-recruiting CXC chemokines in the cerebrospinal fluid despite uncontrolled CNS Candida infection. We phenocopied the human susceptibility in Card9(-/-) mice, which develop uncontrolled brain candidiasis with diminished neutrophil accumulation. The induction of neutrophil-recruiting CXC chemokines is significantly impaired in infected Card9(-/-) brains, from both myeloid and resident glial cellular sources, whereas cell-intrinsic neutrophil chemotaxis is Card9-independent. Taken together, our data highlight the critical role of CARD9-dependent neutrophil trafficking into the CNS and provide novel insight into the CNS fungal susceptibility of CARD9-deficient humans.
C1 [Drummond, Rebecca A.; Collar, Amanda L.; Swamydas, Muthulekha; Rose, Stacey R.; Ferre, Elise M. N.; Yockey, Lynne] NIAID, Fungal Pathogenesis Unit, LCID, NIH, Bethesda, MD 20892 USA.
[Rodriguez, Carlos A.; Lim, Jean K.] Icahn Sch Med Mt Sinai, Dept Microbiol, New York, NY 10029 USA.
[Mendez, Laura M.; Fink, Danielle L.; Kuhns, Douglas B.] Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Neutrophil Monitoring Lab, Applied Dev Res Directorate, Frederick, MD USA.
[Hsu, Amy P.] NIAID, Immunopathogenesis Sect, LCID, NIH, Bethesda, MD 20892 USA.
[Zhai, Bing; Hohl, Tobias M.] Mem Sloan Kettering Canc Ctr, Infect Dis Serv, Dept Med, New York, NY 10021 USA.
[Karauzum, Hatice; Datta, Sandip K.] NIAID, Bacterial Pathogenesis Unit, LCID, NIH, Bethesda, MD 20892 USA.
[Mikelis, Constantinos M.] Texas Tech Univ, Dept Biomed Sci, Sch Pharm, Hlth Sci Ctr, Amarillo, TX USA.
[Lemberg, Kimberly; Kuehn, Hye Sun; Rosenzweig, Sergio D.] NIH, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA.
[Lin, Xin] Univ Texas MD Anderson Canc Ctr, Dept Mol & Cellular Oncol, Div Basic Sci Res, Houston, TX 77030 USA.
[Chittiboina, Prashant] NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA.
[Belhorn, Thomas H.] Univ N Carolina, Dept Pediat, Chapel Hill, NC USA.
[Weimer, Eric T.] Univ N Carolina, Dept Pathol & Lab Med, Chapel Hill, NC USA.
[Hernandez, Michelle L.] Univ N Carolina, Ctr Environm Med Asthma & Lung Biol, Chapel Hill, NC USA.
RP Drummond, RA (reprint author), NIAID, Fungal Pathogenesis Unit, LCID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM lionakism@mail.nih.gov
OI Datta, Sandip/0000-0003-0243-7815; Drummond, Rebecca/0000-0001-5424-7074
FU Division of Intramural Research (DIR), NIAID, NIH; NIH [AI093808,
AI105617]; Burroughs Wellcome Fund; National Cancer Institute, NIH
[HHSN261200800001E]
FX This work was supported by the Division of Intramural Research (DIR),
NIAID, NIH. TMH was supported by NIH grants AI093808 and AI105617, and
by the Burroughs Wellcome Fund. LMM, DLF and DBK were funded by the
National Cancer Institute, NIH, under Contract No. HHSN261200800001E.
The funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 43
TC 5
Z9 5
U1 0
U2 3
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 DEC
PY 2015
VL 11
IS 12
AR e1005293
DI 10.1371/journal.ppat.1005293
PG 32
WC Microbiology; Parasitology; Virology
SC Microbiology; Parasitology; Virology
GA DB2IZ
UT WOS:000368332800021
PM 26679537
ER
PT J
AU Roche, J
Louis, JM
Bax, A
Best, RB
AF Roche, Julien
Louis, John M.
Bax, Ad
Best, Robert B.
TI Pressure-induced structural transition of mature HIV-1 protease from a
combined NMR/MD simulation approach
SO PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS
LA English
DT Article
DE protein folding and stability; high-pressure; packing defects;
conformational fluctuations; cavities; ubiquitin
ID RESIDUAL DIPOLAR COUPLINGS; MOLECULAR-DYNAMICS SIMULATIONS; HIGH
HYDROSTATIC-PRESSURE; CLINICAL INHIBITORS; PROTEINS; ALIGNMENT; WATER;
PERTURBATION; FLUCTUATIONS; RELAXATION
AB We investigate the pressure-induced structural changes in the mature human immunodeficiency virus type 1 protease dimer, using residual dipolar coupling (RDC) measurements in a weakly oriented solution. D-1(NH) RDCs were measured under high-pressure conditions for an inhibitor-free PR and an inhibitor-bound complex, as well as for an inhibitor-free multidrug resistant protease bearing 20 mutations (PR20). While PR20 and the inhibitor-bound PR were little affected by pressure, inhibitor-free PR showed significant differences in the RDCs measured at 600 bar compared with 1 bar. The structural basis of such changes was investigated by MD simulations using the experimental RDC restraints, revealing substantial conformational perturbations, specifically a partial opening of the flaps and the penetration of water molecules into the hydrophobic core of the subunits at high pressure. This study highlights the exquisite sensitivity of RDCs to pressure-induced conformational changes and illustrates how RDCs combined with MD simulations can be used to determine the structural properties of metastable intermediate states on the folding energy landscape.
C1 [Roche, Julien; Louis, John M.; Bax, Ad; Best, Robert B.] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
RP Best, RB (reprint author), NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
EM robertbe@helix.nih.gov
RI Best, Robert/H-7588-2016
OI Best, Robert/0000-0002-7893-3543
FU Intramural Research Program of the National Institute of Diabetes and
Digestive and Kidney Diseases of the National Institutes of Health;
Intramural AIDS Research Fellowship
FX Grant sponsor: Intramural Research Program of the National Institute of
Diabetes and Digestive and Kidney Diseases of the National Institutes of
Health; Grant sponsor: Intramural AIDS Research Fellowship.
NR 40
TC 3
Z9 3
U1 5
U2 17
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0887-3585
EI 1097-0134
J9 PROTEINS
JI Proteins
PD DEC
PY 2015
VL 83
IS 12
BP 2117
EP 2123
DI 10.1002/prot.24931
PG 7
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA DB2IE
UT WOS:000368330700001
PM 26385843
ER
PT J
AU Joo, K
Joung, I
Lee, J
Lee, J
Lee, W
Brooks, B
Lee, SJ
Lee, J
AF Joo, Keehyoung
Joung, Insuk
Lee, Jinhyuk
Lee, Jinwoo
Lee, Weontae
Brooks, Bernard
Lee, Sung Jong
Lee, Jooyoung
TI Protein structure determination by conformational space annealing using
NMR geometric restraints
SO PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS
LA English
DT Article
DE protein structure determination; NMR restraint; ambiguous distance
correction; global optimization
ID GLOBAL OPTIMIZATION; STRUCTURE PREDICTION; CASP7 PREDICTIONS; DYNAMICS;
CRYSTALLOGRAPHY; SPECTROSCOPY; MINIMIZATION; ALGORITHMS; FRAGMENT;
PACKAGE
AB We have carried out numerical experiments to investigate the applicability of the global optimization method of conformational space annealing (CSA) to the enhanced NMR protein structure determination over existing PDB structures. The NMR protein structure determination is driven by the optimization of collective multiple restraints arising from experimental data and the basic stereochemical properties of a protein-like molecule. By rigorous and straightforward application of CSA to the identical NMR experimental data used to generate existing PDB structures, we redetermined 56 recent PDB protein structures starting from fully randomized structures. The quality of CSA-generated structures and existing PDB structures were assessed by multi-objective functions in terms of their consistencies with experimental data and the requirements of protein-like stereochemistry. In 54 out of 56 cases, CSA-generated structures were better than existing PDB structures in the Pareto-dominant manner, while in the remaining two cases, it was a tie with mixed results. As a whole, all structural features tested improved in a statistically meaningful manner. The most improved feature was the Ramachandran favored portion of backbone torsion angles with about 8.6% improvement from 88.9% to 97.5% (P-value <10(-17)). We show that by straightforward application of CSA to the efficient global optimization of an energy function, NMR structures will be of better quality than existing PDB structures. (C) 2015 Wiley Periodicals, Inc.
C1 [Joo, Keehyoung; Joung, Insuk; Lee, Sung Jong; Lee, Jooyoung] Korea Inst Adv Study, Ctr Sil Prot Sci, Seoul 130722, South Korea.
[Joo, Keehyoung] Korea Inst Adv Study, Ctr Adv Computat, Seoul 130722, South Korea.
[Joung, Insuk; Lee, Jooyoung] Korea Inst Adv Study, Sch Computat Sci, Seoul 130722, South Korea.
[Lee, Jinhyuk] Korea Res Inst Biosci & Biotechnol, Korean Bioinformat Ctr KOBIC, Daejeon 305806, South Korea.
[Lee, Jinhyuk] Univ Sci & Technol, Dept Nanobiotechnol & Bioinformat, Daejeon 305350, South Korea.
[Lee, Jinwoo] Kwangwoon Univ, Dept Math, Seoul 139701, South Korea.
[Lee, Weontae] Yonsei Univ, Dept Biochem, Seoul 120749, South Korea.
[Brooks, Bernard] NHLBI, Lab Computat Biol, NIH, Bethesda, MD 20852 USA.
[Lee, Sung Jong] Univ Suwon, Dept Phys, Hwaseong Si 445743, Gyeonggi Do, South Korea.
RP Lee, J (reprint author), Korea Inst Adv Study, Ctr Sil Prot Sci, Seoul 130722, South Korea.
EM jlee@kias.re.kr
FU Korea government (MEST) [2008-0061987]; Korea Research Institute of
Bioscience and Biotechnology (KRIBB) Research Initiative Program;
Research Grant of Kwangwoon University; MEST [NRF-2013R1A2A2A01068963]
FX Grant sponsor: Korea government (MEST); Grant number: 2008-0061987;
Grant sponsors: Korea Research Institute of Bioscience and Biotechnology
(KRIBB) Research Initiative Program (to JHL); Research Grant of
Kwangwoon University (to JWL); and Mid-career Researcher Program (to
WL); Grant sponsor: MEST; Grant number: NRF-2013R1A2A2A01068963.
NR 42
TC 0
Z9 0
U1 2
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0887-3585
EI 1097-0134
J9 PROTEINS
JI Proteins
PD DEC
PY 2015
VL 83
IS 12
BP 2251
EP 2262
DI 10.1002/prot.24941
PG 12
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA DB2IE
UT WOS:000368330700012
PM 26454251
ER
PT J
AU Stepanov, I
Gupta, PC
Dhumal, G
Yershova, K
Toscano, W
Hatsukami, D
Parascandola, M
AF Stepanov, Irina
Gupta, Prakash C.
Dhumal, Gauri
Yershova, Katrina
Toscano, William
Hatsukami, Dorothy
Parascandola, Mark
TI High levels of tobacco-specific N-nitrosamines and nicotine in Chaini
Khaini, a product marketed as snus
SO TOBACCO CONTROL
LA English
DT Article
DE Carcinogens; Nicotine; Harm Reduction; Packaging and Labelling
ID SMOKELESS TOBACCO; MOIST SNUFF; PUBLIC-HEALTH; CANCER; INDIA;
EPIDEMIOLOGY; SMOKING; MOUTH; RISK; PH
AB Introduction Recently, a tobacco product, Chaini Khaini, identified as snus appeared in India. The product marketing emphasises its discreet nature and explicitly claims safety by referring to the existing evidence on Swedish snus. We analysed tobacco-specific nitrosamines and nicotine in 12 samples of Chaini Khaini purchased in 2013 at open markets in India.
Methods Samples were purchased twice: in March 2013 from Mumbai and in November 2013 from Mumbai and Ahmedabad. Chemical constituents were measured by our routine validated methods.
Results Levels of carcinogenic nitrosamines NNN, NNK and NNAL averaged 22.9 (4.9), 2.6 (+/- 1.0) and 3.1 (+/- 1.5)mu g/g tobacco (wet weight), respectively. The levels of NAB, which is normally present in trace levels in tobacco products, ranged from 3.9 to 12.9 mu g/g tobacco. Total nicotine levels in all samples averaged 10.0mg/g tobacco and unprotonated nicotine accounted for an average 95.4% of the total nicotine content.
Conclusions Chaini Khaini, which is labelled as snus and is marketed as a safe alternative to other tobacco products contains very high levels of carcinogenic nitrosamines and biologically available nicotine. Interventions are urgently needed to educate current and potential consumers of this product.
C1 [Stepanov, Irina; Yershova, Katrina; Hatsukami, Dorothy] Univ Minnesota, Masonic Canc Ctr, Minneapolis, MN 55455 USA.
[Stepanov, Irina; Toscano, William] Univ Minnesota, Div Environm Hlth Sci, Minneapolis, MN 55455 USA.
[Gupta, Prakash C.; Dhumal, Gauri] Healis Sekhsaria Inst Publ Hlth, Mumbai, Maharashtra, India.
[Parascandola, Mark] Natl Canc Inst, Tobacco Control Res Branch, Bethesda, MD USA.
RP Stepanov, I (reprint author), Univ Minnesota, Masonic Canc Ctr, Canc & Cardiovasc Res Bldg,2231 6th St SE, Minneapolis, MN 55455 USA.
EM stepa011@umn.edu
OI Stepanov, Irina/0000-0001-5140-8944
FU National Cancer Institute [HHSN261201200392P]; Masonic Cancer Center,
University of Minnesota via NCI [P30 CA077598]
FX This work was supported by the National Cancer Institute contract
HHSN261201200392P and by startup funds to IS from the Masonic Cancer
Center, University of Minnesota via NCI grant P30 CA077598.
NR 23
TC 3
Z9 3
U1 0
U2 2
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0964-4563
EI 1468-3318
J9 TOB CONTROL
JI Tob. Control
PD DEC
PY 2015
VL 24
IS E4
BP E271
EP E274
DI 10.1136/tobaccocontrol-2014-051744
PG 4
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA DA5HQ
UT WOS:000367834300008
PM 25217658
ER
PT J
AU Custer, B
Sheon, N
Siedle-Khan, B
Pollack, L
Spencer, B
Bialkowski, W
D'Andrea, P
Sullivan, M
Glynn, S
Williams, A
AF Custer, Brian
Sheon, Nicolas
Siedle-Khan, Bob
Pollack, Lance
Spencer, Bryan
Bialkowski, Walter
D'Andrea, Pam
Sullivan, Marian
Glynn, Simone
Williams, Alan
CA NHLBI Recipient Epidemiology Donor
TI Blood donor deferral for men who have sex with men: the Blood Donation
Rules Opinion Study (Blood DROPS)
SO TRANSFUSION
LA English
DT Article
ID TRANSFUSION-TRANSMITTED HIV; EVER HAD SEX; GAY MEN; RISK; POLICY;
IMPACT; DISCRIMINATION; EXCLUSION; ENGLAND; WALES
AB BACKGROUND: In the United States, any man who discloses having had sex with another man (MSM) even once since 1977 is currently deferred from donating blood. A study was conducted to assess noncompliance with the policy at four geographically dispersed blood centers.
STUDY DESIGN AND METHODS: Male donors 18+ years of age with e-mail addresses were randomly selected and invited to complete a confidential online survey between August and October 2013. No additional recruitment e-mails were sent. Survey content included demographics, sexual history, donation history, compliance with the policy, and opinions about current and modified policies.
RESULTS: Response rate was 11.5% but varied by center (6.3% to 21.7%). Of 3183 completed surveys, 2.6% of respondents (95% confidence interval, 2.1%-3.2%) reported donation after male-male sex. Noncompliance was not statistically different among the centers (p=0.1), but was related to age with 5.7, 4.6, 2.5, and 1.0% of donors 18 to 24, 25 to 34, 35 to 54, and 50+ years of age, respectively, reporting noncompliance (p<0.001). Of all respondents, 6.8% reported at least six female and 0.3% reported at least six male sex partners in the past 5 years. Opinions about the current MSM policy were mixed with noncomplying donors more supportive of change than complying donors. Approximatey half of noncompliers indicated they would adhere to a 1-year deferral.
CONCLUSION: Noncompliance with the MSM policy is evident and may be increasing compared to earlier data. Any change from the current policy will require close monitoring to determine whether it affects residual risk of HIV in the US blood supply.
C1 [Custer, Brian] UCSF, Blood Syst Res Inst, San Francisco, CA USA.
[Custer, Brian] Univ Calif San Francisco, Dept Lab Med, San Francisco, CA 94143 USA.
[Sheon, Nicolas; Siedle-Khan, Bob; Pollack, Lance] UCSF, Ctr AIDS Prevent Studies, San Francisco, CA USA.
[Spencer, Bryan] Amer Red Cross, Dedham, MA USA.
[Bialkowski, Walter] BloodCtr Wisconsin, Milwaukee, WI USA.
[D'Andrea, Pam] Inst Transfus Med, Pittsburgh, PA USA.
[Sullivan, Marian] RTI Int, Rockville, MD USA.
[Glynn, Simone] NHLBI, Bethesda, MD 20892 USA.
[Williams, Alan] US FDA, Silver Spring, MD USA.
RP Custer, B (reprint author), Blood Syst Res Inst, 270 Mason Ave, San Francisco, CA 94118 USA.
EM bcuster@bloodsystems.org
FU US FDA; NHLBI REDS-III program
FX This study was funded by the US FDA and the NHLBI REDS-III program.
NR 34
TC 9
Z9 9
U1 1
U2 4
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 DEC
PY 2015
VL 55
IS 12
BP 2826
EP 2834
DI 10.1111/trf.13247
PG 9
WC Hematology
SC Hematology
GA DA6YB
UT WOS:000367950600010
PM 26202349
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 Demographic and clinical variables affecting mid-to late-life
trajectories of plasma ceramide and dihydroceramide species
SO AGING CELL
LA English
DT Article
DE aging; ceramide; dihydroceramide; human; longitudinal; sex differences
ID INSULIN-RESISTANCE; SPHINGOLIPID METABOLISM; MASS-SPECTROMETRY; DISEASE;
SPAN; RISK; ALZHEIMERS; LIPIDOMICS; PROTEIN; STRESS
AB It has been increasingly recognized at the basic science level that perturbations in ceramide metabolism are associated with the development and progression of many age-related diseases. However, the translation of this work to the clinic has lagged behind. Understanding the factors longitudinally associated with plasma ceramides and dihydroceramides (DHCer) at the population level and how these lipid levels change with age, and by sex, is important for the clinical development of future therapeutics and biomarkers focused on ceramide metabolism. We, therefore, examined factors cross-sectionally and longitudinally associated with plasma concentrations of ceramides and DHCer among Baltimore Longitudinal Study of Aging participants (n = 992; 3960 total samples), aged 55 years and older, with plasma at a mean of 4.1 visits (range 2-6). Quantitative analyses were performed on a high-performance liquid chromatography-coupled electrospray ionization tandem mass spectrometer. Linear mixed models were used to assess the relationships between plasma ceramide and DHCer species and demographics, diseases, medications, and lifestyle factors. Women had higher plasma concentrations of most ceramide and DHCer species and showed steeper trajectories of age-related increases compared to men. Ceramides and DHCer were more associated with waist-hip ratio than body mass index. Plasma cholesterol and triglycerides, prediabetes, and diabetes were associated with ceramides and DHCer, but the relationship showed specificity to the acyl chain length and saturation. These results demonstrate the importance of examining the individual species of ceramides and DHCer, and of establishing whether intra-individual age- and sex-specific changes occur in synchrony to disease onset and progression.
C1 [Mielke, Michelle M.] Mayo Clin, Dept Hlth Sci Res, Rochester, MN 55905 USA.
[Mielke, Michelle M.] Mayo Clin, Dept Neurol, Rochester, MN 55905 USA.
[Bandaru, Veera Venkata Ratnam; Haughey, Norman J.] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21224 USA.
[Han, Dingfen; Haughey, Norman J.] Johns Hopkins Univ, Sch Med, Psychiat, Baltimore, MD 21224 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 45
TC 5
Z9 5
U1 0
U2 3
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 DEC
PY 2015
VL 14
IS 6
BP 1014
EP 1023
DI 10.1111/acel.12369
PG 10
WC Cell Biology; Geriatrics & Gerontology
SC Cell Biology; Geriatrics & Gerontology
GA DA2XT
UT WOS:000367661200010
PM 26193443
ER
PT J
AU Li, Q
Wang, SR
Milot, E
Bergeron, P
Ferrucci, L
Fried, LP
Cohen, AA
AF Li, Qing
Wang, Shengrui
Milot, Emmanuel
Bergeron, Patrick
Ferrucci, Luigi
Fried, Linda P.
Cohen, Alan A.
TI Homeostatic dysregulation proceeds in parallel in multiple physiological
systems
SO AGING CELL
LA English
DT Article
DE aging; biomarker; homeostasis; multi-system dysregulation; physiology;
statistical distance
ID ALLOSTATIC LOAD; LONGEVITY; AGE; FRAILTY; HEALTH; TRAJECTORIES;
POPULATION; MORTALITY; DECLINE
AB An increasing number of aging researchers believes that multisystem physiological dysregulation may be a key biological mechanism of aging, but evidence of this has been sparse. Here, we used biomarker data on nearly 33 000 individuals from four large datasets to test for the presence of multi-system dysregulation. We grouped 37 biomarkers into six a priori groupings representing physiological systems (lipids, immune, oxygen transport, liver function, vitamins, and electrolytes), then calculated dysregulation scores for each system in each individual using statistical distance. Correlations among dysregulation levels across systems were generally weak but significant. Comparison of these results to dysregulation in arbitrary 'systems' generated by random grouping of biomarkers showed that a priori knowledge effectively distinguished the true systems in which dysregulation proceeds most independently. In other words, correlations among dysregulation levels were higher using arbitrary systems, indicating that only a priori systems identified distinct dysregulation processes. Additionally, dysregulation of most systems increased with age and significantly predicted multiple health outcomes including mortality, frailty, diabetes, heart disease, and number of chronic diseases. The six systems differed in how well their dysregulation scores predicted health outcomes and age. These findings present the first unequivocal demonstration of integrated multi-system physiological dysregulation during aging, demonstrating that physiological dysregulation proceeds neither as a single global process nor as a completely independent process in different systems, but rather as a set of system-specific processes likely linked through weak feedback effects. These processes - probably many more than the six measured here - are implicated in aging.
C1 [Li, Qing; Milot, Emmanuel; Bergeron, Patrick; Cohen, Alan A.] Univ Sherbrooke, Dept Family Med, Grp Rech PRIMUS, Sherbrooke, PQ J1H 5N4, Canada.
[Wang, Shengrui] Univ Sherbrooke, Dept Comp Sci, Sherbrooke, PQ J1K 2R1, Canada.
[Ferrucci, Luigi] MedStar Harbor Hosp, Natl Inst Hlth, Natl Inst Aging, Translat Gerontol Branch,Longitudinal Studies Sec, Baltimore, MD 21225 USA.
[Fried, Linda P.] Columbia Univ, Mailman Sch Publ Hlth, New York, NY 10032 USA.
RP Cohen, AA (reprint author), Univ Sherbrooke, Dept Family Med, Grp Rech PRIMUS, 3001 12E Ave N, Sherbrooke, PQ J1H 5N4, Canada.
EM alan.cohen@usherbrooke.ca
FU FRQ-S; CIHR [110789, 120305, 119485]; NSERC [402079-2011]; National
Institute on Aging
FX AAC is a member of the FRQ-S-supported Centre de recherche sur le
vieillissement and Centre de recherche du CHUS, and is a funded Research
Scholar of the FRQ-S. This research was supported by CIHR grant #s
110789, 120305, 119485 and by NSERC Discovery Grant # 402079-2011, as
well as by the Intramural Research Program of the National Institute on
Aging.
NR 43
TC 5
Z9 5
U1 0
U2 5
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 DEC
PY 2015
VL 14
IS 6
BP 1103
EP 1112
DI 10.1111/acel.12402
PG 10
WC Cell Biology; Geriatrics & Gerontology
SC Cell Biology; Geriatrics & Gerontology
GA DA2XT
UT WOS:000367661200019
PM 26416593
ER
PT J
AU Hankins, JS
McCarville, MB
Rankine-Mullings, A
Reid, ME
Lobo, CLC
Moura, PG
Ali, S
Soares, DP
Aldred, K
Jay, DW
Aygun, B
Bennett, J
Kang, GL
Goldsmith, JC
Smeltzer, MP
Boyett, JM
Ware, RE
AF Hankins, Jane S.
McCarville, Mary Beth
Rankine-Mullings, Angela
Reid, Marvin E.
Lobo, Clarisse L. C.
Moura, Patricia G.
Ali, Susanna
Soares, Deanne P.
Aldred, Karen
Jay, Dennis W.
Aygun, Banu
Bennett, John
Kang, Guolian
Goldsmith, Jonathan C.
Smeltzer, Matthew P.
Boyett, James M.
Ware, Russell E.
TI Prevention of conversion to abnormal transcranial Doppler with
hydroxyurea in sickle cell anemia: A Phase III international randomized
clinical trial
SO AMERICAN JOURNAL OF HEMATOLOGY
LA English
DT Article
ID FLOW VELOCITIES; YOUNG-CHILDREN; BABY HUG; DISEASE; STROKE; THERAPY;
EVENTS; ULTRASONOGRAPHY; PERSPECTIVE; EXPERIENCE
AB Children with sickle cell anemia (SCA) and conditional transcranial Doppler (TCD) ultrasound velocities (170-199 cm/sec) may develop stroke. However, with limited available clinical data, the current standard of care for conditional TCD velocities is observation. The efficacy of hydroxyurea in preventing conversion from conditional to abnormal TCD (>= 200 cm/sec), which confers a higher stroke risk, has not been studied prospectively in a randomized trial. Sparing Conversion to Abnormal TCD Elevation (SCATE #NCT01531387) was a National Heart, Lung, and Blood Institute-funded Phase III multicenter international clinical trial comparing alternative therapy (hydroxyurea) to standard care (observation) to prevent conversion from conditional to abnormal TCD velocity in children with SCA. SCATE enrolled 38 children from the United States, Jamaica, and Brazil [HbSS (36), HbS beta(0)-thalassemia (1), and HbSD (1), median age=5.4 years (range, 2.7-9.8)]. Because of the slow patient accrual and administrative delays, SCATE was terminated early. In an intention-to-treat analysis, the cumulative incidence of abnormal conversion was 9% (95% CI=0-35%) in the hydroxyurea arm and 47% (95% CI=6-81%) in observation arm at 15 months (P=0.16). In post hoc analysis according to treatment received, significantly fewer children on hydroxyurea converted to abnormal TCD velocities when compared with observation (0% vs. 50%, P=0.02). After a mean of 10.1 months, a significant change in mean TCD velocity was observed with hydroxyurea treatment (-15.5 vs. +10.2 cm/sec, P=0.02). No stroke events occurred in either arm. Hydroxyurea reduces TCD velocities in children with SCA and conditional velocities. (C) 2015 Wiley Periodicals, Inc.
C1 [Hankins, Jane S.; McCarville, Mary Beth; Jay, Dennis W.; Kang, Guolian; Smeltzer, Matthew P.; Boyett, James M.] St Jude Childrens Res Hosp, Dept Hematol, Memphis, TN 38105 USA.
[Rankine-Mullings, Angela; Reid, Marvin E.; Ali, Susanna; Soares, Deanne P.; Aldred, Karen] Univ W Indies, Res Inst Trop Med, Sickle Cell Unit, Kingston 7, Jamaica.
[Lobo, Clarisse L. C.; Moura, Patricia G.] Inst De Hematol Arthur Siqueira Cavalcanti HEMORI, Rio De Janeiro, Brazil.
[Aygun, Banu] Cohen Childrens Med Ctr New York, Div Pediat Hematol Oncol & Stem Cell Transplantat, New Hyde Pk, NY USA.
[Bennett, John] Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA.
[Goldsmith, Jonathan C.] NHLBI, Bethesda, MD 20892 USA.
[Ware, Russell E.] Cincinnati Childrens Hosp Med Ctr, Div Hematol, Cincinnati, OH 45229 USA.
RP Hankins, JS (reprint author), St Jude Childrens Res Hosp, Dept Hematol, 262 Danny Thomas Pl,MS 800, Memphis, TN 38105 USA.
EM jane.hankins@stjude.org
OI Reid, Marvin/0000-0003-4005-9384
FU National Hearth Lung and Blood Institute [5R01HL098239]
FX Contract grant sponsor: National Hearth Lung and Blood Institute;
Contract grant number: 5R01HL098239.
NR 36
TC 5
Z9 5
U1 0
U2 1
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 DEC
PY 2015
VL 90
IS 12
BP 1099
EP 1105
DI 10.1002/ajh.24198
PG 7
WC Hematology
SC Hematology
GA DA2ZS
UT WOS:000367666300013
PM 26414435
ER
PT J
AU Donkervoort, S
Papadaki, M
de Winter, JM
Neu, MB
Kirschner, J
Bolduc, V
Yang, ML
Gibbons, MA
Hu, Y
Dastgir, J
Leach, ME
Rutkowski, A
Foley, AR
Kruger, M
Wartchow, EP
McNamara, E
Ong, R
Nowak, KJ
Laing, NG
Clarke, NF
Ottenheijm, CAC
Marston, SB
Bonnemann, CG
AF Donkervoort, Sandra
Papadaki, Maria
de Winter, Josine M.
Neu, Matthew B.
Kirschner, Janbernd
Bolduc, Veronique
Yang, Michele L.
Gibbons, Melissa A.
Hu, Ying
Dastgir, Jahannaz
Leach, Meganne E.
Rutkowski, Anne
Foley, A. Reghan
Krueger, Marcus
Wartchow, Eric P.
McNamara, Elyshia
Ong, Royston
Nowak, Kristen J.
Laing, Nigel G.
Clarke, Nigel F.
Ottenheijm, Coen A. C.
Marston, Steven B.
Boennemann, Carsten G.
TI TPM3 Deletions Cause a Hypercontractile Congenital Muscle Stiffness
Phenotype
SO ANNALS OF NEUROLOGY
LA English
DT Article
ID NEMALINE MYOPATHY PATIENTS; TROPONIN-I PHOSPHORYLATION;
ALPHA-TROPOMYOSIN; THIN FILAMENT; F-ACTIN; ENERGY LANDSCAPES;
HEART-FAILURE; CAUSE GAIN; MUTATIONS; SENSITIVITY
AB Objective: Mutations in TPM3, encoding Tpm3.12, cause a clinically and histopathologically diverse group of myopathies characterized by muscle weakness. We report two patients with novel de novo Tpm3.12 single glutamic acid deletions at positions Delta E218 and Delta E224, resulting in a significant hypercontractile phenotype with congenital muscle stiffness, rather than weakness, and respiratory failure in one patient.
Methods: The effect of the Tpm3.12 deletions on the contractile properties in dissected patient myofibers was measured. We used quantitative in vitro motility assay to measure Ca2+ sensitivity of thin filaments reconstituted with recombinant Tpm3.12 Delta E218 and Delta E224.
Results: Contractility studies on permeabilized myofibers demonstrated reduced maximal active tension from both patients with increased Ca2+ sensitivity and altered cross-bridge cycling kinetics in Delta DE224 fibers. In vitro motility studies showed a two-fold increase in Ca2+ sensitivity of the fraction of filaments motile and the filament sliding velocity concentrations for both mutations.
Interpretation: These data indicate that Tpm3.12 deletions Delta E218 and Delta E224 result in increased Ca2+ sensitivity of the troponin-tropomyosin complex, resulting in abnormally active interaction of the actin and myosin complex. Both mutations are located in the charged motifs of the actin-binding residues of tropomyosin 3, thus disrupting the electrostatic interactions that facilitate accurate tropomyosin binding with actin necessary to prevent the on-state. The mutations destabilize the off-state and result in excessively sensitized excitation-contraction coupling of the contract-ile apparatus. This work expands the phenotypic spectrum of TPM3-related disease and provides insights into the pathophysiological mechanisms of the actin-tropomyosin complex.
C1 [Donkervoort, Sandra; Neu, Matthew B.; Bolduc, Veronique; Hu, Ying; Dastgir, Jahannaz; Leach, Meganne E.; Foley, A. Reghan; Boennemann, Carsten G.] NIH, Neuromuscular & Neurogenet Disorders Childhood Se, Bethesda, MD 20892 USA.
[Papadaki, Maria; Marston, Steven B.] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, London, England.
[de Winter, Josine M.; Ottenheijm, Coen A. C.] Vrije Univ Amsterdam Med Ctr, Dept Physiol, Amsterdam, Netherlands.
[Kirschner, Janbernd] Univ Med Ctr Freiburg, Dept Neuropediat & Muscle Disorders, Freiburg, Germany.
[Yang, Michele L.] Univ Colorado, Sch Med, Sect Child Neurol, Dept Pediat & Neurol, Aurora, CO USA.
[Gibbons, Melissa A.] Univ Colorado, Denver Sch Med, Aurora, CO USA.
[Leach, Meganne E.] Childrens Natl Hlth Syst, Washington, DC USA.
[Rutkowski, Anne] Kaiser Southern Calif Permanente Med Grp, Cure CMD, Olathe, KS USA.
[Krueger, Marcus] Univ Med Ctr Freiburg, Dept Gen Pediat Adolescent Med & Neonatol, Freiburg, Germany.
[Wartchow, Eric P.] Childrens Hosp Colorado, Dept Pathol, Aurora, CO USA.
[McNamara, Elyshia; Ong, Royston; Nowak, Kristen J.; Laing, Nigel G.] Univ Western Australia, Neuromuscular Dis Lab, Med Res Ctr, Fac Med Dent & Hlth Sci, Crawley, WA, Australia.
[McNamara, Elyshia; Ong, Royston; Nowak, Kristen J.; Laing, Nigel G.] Queen Elizabeth II Med Ctr, Harry Perkins Inst Med Res, Perth, WA, Australia.
[Clarke, Nigel F.] Univ Sydney, Inst Neurosci & Muscle Res, Childrens Hosp Westmead, Sydney, NSW 2006, Australia.
RP Bonnemann, CG (reprint author), NIH, Porter Neurosci Res Ctr, 35 Convent Dr,Bldg 35,Room 2A-116, Bethesda, MD 20892 USA.
EM carsten.bonnemann@nih.gov
RI Kirschner, Janbernd/H-7418-2016
OI Kirschner, Janbernd/0000-0003-1618-7386
FU Australian National Health and Medical Research Council [APP1002147,
APP1022707]; Australian Research Council [FT100100734]; British Heart
Foundation [RG/11/20/29266, FS/12/24/29568]
FX This study was supported by an Australian National Health and Medical
Research Council fellowship (APP1002147, N.G.L.) and project grant
(APP1022707, E.M., R.O.); an Australian Research Council Future
Fellowship (FT100100734, K.J.N.); and grants from the British Heart
Foundation (RG/11/20/29266, FS/12/24/29568, S.B.M., M.K.).
NR 40
TC 3
Z9 3
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0364-5134
EI 1531-8249
J9 ANN NEUROL
JI Ann. Neurol.
PD DEC
PY 2015
VL 78
IS 6
BP 982
EP 994
DI 10.1002/ana.24535
PG 13
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA DA3DY
UT WOS:000367678100014
PM 26418456
ER
PT J
AU Hu, GW
McQuiston, T
Bernard, A
Park, YD
Qiu, J
Vural, A
Zhang, NN
Waterman, SR
Blewett, NH
Myers, TG
Maraia, RJ
Kehrl, JH
Uzel, G
Klionsky, DJ
Williamson, PR
AF Hu, Guowu
McQuiston, Travis
Bernard, Amelie
Park, Yoon-Dong
Qiu, Jin
Vural, Ali
Zhang, Nannan
Waterman, Scott R.
Blewett, Nathan H.
Myers, Timothy G.
Maraia, Richard J.
Kehrl, John H.
Uzel, Gulbu
Klionsky, Daniel J.
Williamson, Peter R.
TI TOR-dependent post-transcriptional regulation of autophagy
SO AUTOPHAGY
LA English
DT Editorial Material
DE autoimmunity; autophagy; phosphorylation; TOR; translation
AB Regulation of autophagy is required to maintain cellular equilibrium and prevent disease. While extensive study of post-translational mechanisms has yielded important insights into autophagy induction, less is known about post-transcriptional mechanisms that could potentiate homeostatic control. In our study, we showed that the RNA-binding protein, Dhh1 in Saccharomyces cerevisiae and Vad1 in the pathogenic yeast Cryptococcusneoformans is involved in recruitment and degradation of key autophagy mRNAs. In addition, phosphorylation of the decapping protein Dcp2 by the target of rapamycin (TOR), facilitates decapping and degradation of autophagy-related mRNAs, resulting in repression of autophagy under nutrient-replete conditions. The post-transcriptional regulatory process is conserved in both mouse and human cells and plays a role in autophagy-related modulation of the inflammasome product IL1B. These results were then applied to provide mechanistic insight into autoimmunity of a patient with a PIK3CD/p110 gain-of-function mutation. These results thus identify an important new post-transcriptional mechanism of autophagy regulation that is highly conserved between yeast and mammals.
C1 [Hu, Guowu; McQuiston, Travis; Park, Yoon-Dong; Qiu, Jin; Zhang, Nannan; Waterman, Scott R.; Uzel, Gulbu; Williamson, Peter R.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
[Bernard, Amelie; Klionsky, Daniel J.] Univ Michigan, Inst Life Sci, Ann Arbor, MI 48109 USA.
[Vural, Ali; Kehrl, John H.] NIAID, Lab Immunoregulat, NIH, Bethesda, MD 20892 USA.
[Blewett, Nathan H.; Maraia, Richard J.] NICHHD, Intramural Res Program Genom Differentiat, NIH, Bethesda, MD 20892 USA.
[Myers, Timothy G.] NIAID, Genom Technol Sect, Res Technol Branch, NIH, Bethesda, MD 20892 USA.
RP Williamson, PR (reprint author), NIAID, Lab Clin Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM williamsonpr@mail.nih.gov
FU NIGMS NIH HHS [R01 GM053396, GM053396]
NR 6
TC 1
Z9 1
U1 3
U2 7
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 DEC
PY 2015
VL 11
IS 12
BP 2390
EP 2392
DI 10.1080/15548627.2015.1091142
PG 3
WC Cell Biology
SC Cell Biology
GA DA4XO
UT WOS:000367806300029
PM 26569496
ER
PT J
AU Lewis, DEA
Adhya, S
AF Lewis, Dale E. A.
Adhya, Sankar
TI Molecular Mechanisms of Transcription Initiation at gal Promoters and
their Multi-Level Regulation by GalR, CRP and DNA Loop
SO BIOMOLECULES
LA English
DT Review
DE activation; repression; DNA looping; transcription; galactose operon
ID AMP RECEPTOR PROTEIN; COLI GALACTOSE OPERON; OPEN COMPLEX-FORMATION;
POLYMERASE ALPHA-SUBUNIT; CAP-DEPENDENT PROMOTERS; GENE ACTIVATOR
PROTEIN; HISTONE-LIKE PROTEINS; ESCHERICHIA-COLI; RNA-POLYMERASE;
CYCLIC-AMP
AB Studying the regulation of transcription of the gal operon that encodes the amphibolic pathway of d-galactose metabolism in Escherichia coli discerned a plethora of principles that operate in prokaryotic gene regulatory processes. In this chapter, we have reviewed some of the more recent findings in gal that continues to reveal unexpected but important mechanistic details. Since the operon is transcribed from two overlapping promoters, P1 and P2, regulated by common regulatory factors, each genetic or biochemical experiment allowed simultaneous discernment of two promoters. Recent studies range from genetic, biochemical through biophysical experiments providing explanations at physiological, mechanistic and single molecule levels. The salient observations highlighted here are: the axiom of determining transcription start points, discovery of a new promoter element different from the known ones that influences promoter strength, occurrence of an intrinsic DNA sequence element that overrides the transcription elongation pause created by a DNA-bound protein roadblock, first observation of a DNA loop and determination its trajectory, and piggybacking proteins and delivering to their DNA target.
C1 [Lewis, Dale E. A.; Adhya, Sankar] NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Lewis, DEA (reprint author), NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
EM lewisdal@mail.nih.gov; adhyas@mail.nih.gov
FU Intramural NIH HHS
NR 87
TC 1
Z9 1
U1 1
U2 3
PU MDPI AG
PI BASEL
PA POSTFACH, CH-4005 BASEL, SWITZERLAND
SN 2218-273X
J9 BIOMOLECULES
JI Biomolecules
PD DEC
PY 2015
VL 5
IS 4
BP 2782
EP 2807
DI 10.3390/biom5042782
PG 26
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA DA1DW
UT WOS:000367537500026
PM 26501343
ER
PT J
AU Gupta, S
Yui, JC
Xu, DH
Fitzhugh, CD
Clark, C
Siddiqui, S
Conrey, AK
Kato, GJ
Minniti, CP
AF Gupta, Sarthak
Yui, Jennifer C.
Xu, Dihua
Fitzhugh, Courtney D.
Clark, Caroline
Siddiqui, Salahuddin
Conrey, Anna K.
Kato, Gregory J.
Minniti, Caterina P.
TI Gout and sickle cell disease: not all pain is sickle cell pain
SO BRITISH JOURNAL OF HAEMATOLOGY
LA English
DT Letter
DE inflammation; red blood cell disorders; sickle cell disease; gout;
arthritis; pain
ID HYPERURICEMIA; ANEMIA
C1 [Gupta, Sarthak] NIAMSD, NIH, Bethesda, MD 20892 USA.
[Yui, Jennifer C.; Xu, Dihua; Fitzhugh, Courtney D.; Clark, Caroline; Siddiqui, Salahuddin; Conrey, Anna K.; Minniti, Caterina P.] NHLBI, NIH, Bethesda, MD 20892 USA.
[Kato, Gregory J.] Univ Pittsburg, Dept Med, Vasc Med Inst, Pittsburgh, PA USA.
RP Gupta, S (reprint author), NIAMSD, NIH, Bethesda, MD 20892 USA.
EM cminniti@montefiore.org
RI Kato, Gregory/I-7615-2014
OI Kato, Gregory/0000-0003-4465-3217
FU Intramural NIH HHS [Z99 HL999999]
NR 10
TC 2
Z9 2
U1 0
U2 1
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 DEC
PY 2015
VL 171
IS 5
BP 872
EP 875
DI 10.1111/bjh.13433
PG 4
WC Hematology
SC Hematology
GA DA4AB
UT WOS:000367741400021
PM 25892648
ER
PT J
AU Cantor, D
AF Cantor, David
TI A History of Lung Cancer: The Recalcitrant Disease
SO BULLETIN OF THE HISTORY OF MEDICINE
LA English
DT Book Review
C1 [Cantor, David] NIH, Off Hist, Bethesda, MD 20892 USA.
RP Cantor, D (reprint author), NIH, Off Hist, Bldg 10, Bethesda, MD 20892 USA.
NR 1
TC 0
Z9 0
U1 1
U2 1
PU JOHNS HOPKINS UNIV PRESS
PI BALTIMORE
PA JOURNALS PUBLISHING DIVISION, 2715 NORTH CHARLES ST, BALTIMORE, MD
21218-4363 USA
SN 0007-5140
EI 1086-3176
J9 B HIST MED
JI Bull. Hist. Med.
PD WIN
PY 2015
VL 89
IS 4
BP 836
EP 838
PG 3
WC Health Care Sciences & Services; History & Philosophy Of Science
SC Health Care Sciences & Services; History & Philosophy of Science
GA DA1LX
UT WOS:000367558400032
ER
PT J
AU Vedham, V
Verma, M
Mahabir, S
AF Vedham, Vidya
Verma, Mukesh
Mahabir, Somdat
TI Early-life exposures to infectious agents and later cancer development
SO CANCER MEDICINE
LA English
DT Review
DE Cancer; early life exposure; infectious agents; perinatal transmission
ID EPSTEIN-BARR-VIRUS; HEPATITIS-B VACCINATION; DNA-DAMAGE RESPONSE; HTLV-I
INFECTION; MOTHER-TO-CHILD; HEPATOCELLULAR-CARCINOMA;
HUMAN-PAPILLOMAVIRUS; NASOPHARYNGEAL CARCINOMA; BURKITTS-LYMPHOMA;
IMMUNE-RESPONSES
AB There is a growing understanding that several infectious agents are acquired in early life and this is the reason why available vaccines target the new born, infants, and adolescents. Infectious agents are associated with cancer development and it is estimated that about 20% of the world's cancer burden is attributed to infectious agents. There is a growing evidence that certain infectious agents acquired in early life can give rise to cancer development, but estimates of the cancer burden from this early-life acquisition is unknown. In this article, we have selected five cancers (cervical, liver, Burkitt's lymphoma-leukemia, nasopharyngeal carcinoma, and adult T-cell leukemia-lymphoma) and examine their links to infectious agents (HPV, HBV, HCV, EBV, and HTLV-1) acquired in early life. For these agents, the acquisition in early life is from mother-to-child transmission, perinatal contact (with genital tract secretions, amniotic fluids, blood, and breast milk), saliva, sexual intercourse, and blood transfusion. We also discuss prevention strategies, address future directions, and propose mechanisms of action after a long latency period from the time of acquisition of the infectious agent in early life to cancer development.
C1 [Vedham, Vidya; Verma, Mukesh] NCI, Methods & Technol Branch, NIH, Rockville, MD 20850 USA.
[Mahabir, Somdat] NCI, Environm Epidemiol Branch, Epidemiol & Genom Res Program, Div Canc Control & Populat Sci,NIH, Rockville, MD 20850 USA.
RP Mahabir, S (reprint author), NCI, Environm Epidemiol Branch, Epidemiol & Genom Res Program, Div Canc Control & Populat Sci,NIH, Room 4E112,9609 Med Ctr Dr, Rockville, MD 20850 USA.
EM mahabir@mail.nih.gov
NR 146
TC 3
Z9 4
U1 3
U2 13
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 DEC
PY 2015
VL 4
IS 12
BP 1908
EP 1922
DI 10.1002/cam4.538
PG 15
WC Oncology
SC Oncology
GA DA5MI
UT WOS:000367846800014
PM 26377256
ER
PT J
AU Selker, HP
Buse, JB
Califf, RM
Carter, R
Cooper, DM
Davis, J
Ford, DE
Galassetti, P
Guay-Woodford, L
Huggins, GS
Kasper, A
Kieburtz, K
Kirby, A
Klein, AK
Kline, J
Neill, RT
Rape, M
Reichgott, DJ
Rojevsky, S
Rosenthal, GE
Rubinstein, EP
Shepherd, A
Stacy, M
Terrin, N
Wallace, M
Welch, L
AF Selker, Harry P.
Buse, John B.
Califf, Robert M.
Carter, Robert
Cooper, Dan M.
Davis, Jonathan
Ford, Daniel E.
Galassetti, Pietro
Guay-Woodford, Lisa
Huggins, Gordon S.
Kasper, Amanda
Kieburtz, Karl
Kirby, Aaron
Klein, Andreas K.
Kline, Joel
O' Neill, Robert T.
Rape, Marie
Reichgott, Douglas J.
Rojevsky, Svetlana
Rosenthal, Gary E.
Rubinstein, Eric P.
Shepherd, Amy
Stacy, Mark
Terrin, Norma
Wallace, Mark
Welch, Lisa
TI CTSA Consortium Consensus Scientific Review Committee (SRC) Working
Group Report on the SRC Processes
SO CTS-CLINICAL AND TRANSLATIONAL SCIENCE
LA English
DT Article
DE translational research; clinical trials; outcomes research
AB Human research projects must have a scientifically valid study design, analytic plan, and be operationally feasible in order to be successfully completed and thus to have translational impact. To ensure this, institutions that conduct clinical research should have a scientific review process prior to submission to the Institutional Review Committee (IRB). This paper reports the Clinical and Translational Science Award (CTSA) Consortium Scientific Review Committee (SRC) Consensus Working Group's proposed framework for a SRC process. Recommendations are provided for institutional support and roles of CTSAs, multisite research, criteria for selection of protocols that should be reviewed, roles of committee members, application process, and committee process. Additionally, to support the SCR process effectively, and to ensure efficiency, the Working Group recommends information technology infrastructures and evaluation metrics to determine outcomes are provided.
C1 [Selker, Harry P.; Davis, Jonathan; Kirby, Aaron; Rojevsky, Svetlana; Shepherd, Amy; Terrin, Norma; Welch, Lisa] Tufts Med Ctr, Tufts Clin & Translat Sci Inst, Boston, MA 02111 USA.
[Buse, John B.; Rape, Marie] Univ N Carolina, Translat & Clin Sci Inst, Chapel Hill, NC USA.
[Califf, Robert M.; Stacy, Mark] Duke Univ, Duke Translat Med Inst, Durham, NC USA.
[Carter, Robert] NIH, Bethesda, MD 20892 USA.
[Cooper, Dan M.; Galassetti, Pietro] Univ Calif Irvine, Inst Clin & Translat Sci, Irvine, CA USA.
[Ford, Daniel E.] Johns Hopkins Univ, Inst Clin & Translat Res, Baltimore, MD USA.
[Guay-Woodford, Lisa; Kasper, Amanda] Clin & Translat Sci Inst Childrens Natl, Washington, DC USA.
[Huggins, Gordon S.; Klein, Andreas K.; Reichgott, Douglas J.] Tufts Med Ctr, Boston, MA USA.
[Kieburtz, Karl; Rubinstein, Eric P.] Univ Rochester, Med Ctr, Clin & Translat Sci Inst, Rochester, NY 14642 USA.
[Kline, Joel; Rosenthal, Gary E.] Univ Iowa, Inst Clin & Translat Sci, Iowa City, IA USA.
[O' Neill, Robert T.] US FDA, Silver Spring, MD USA.
[Wallace, Mark] Univ Calif San Diego, Clin & Translat Res Inst, San Diego, CA 92103 USA.
RP Selker, HP (reprint author), Tufts Med Ctr, Tufts Clin & Translat Sci Inst, Boston, MA 02111 USA.
EM HSelker@tuftsmedicalcenter.org
FU National Institutes of Health Clinical and Translational Science Awards
[UL1 TR001064]; University of North Carolina at Chapel Hill,
Translational & Clinical Sciences Institute [1UL1TR001111]; Duke
Translational Medicine Institute, Duke University, Institute for
Clinical and Translational Science [UL1TR001117]; University of
California, Irvine, Institute for Clinical and Translational Research
[UL1TR000153]; Johns Hopkins University, Institute for Clinical &
Translational Research [UL1TR001079]; Clinical and Translational Science
Institute at Children's National Center for Translational Science
[UL1TR000075]; University of Rochester Clinical and Translational
Science Institute [UL1TR000042]; Institute for Clinical and
Translational Science at the University of Iowa [U54TR001013]; Clinical
and Translational Research Institute, University of California, San
Diego [UL1TR000100]
FX This paper was supported by an administrative supplement award to the
Tufts CTSI from the National Institutes of Health Clinical and
Translational Science Awards (UL1 TR001064), with additional support
from the Working Group's affiliated CTSAs. The affiliated CTSAs include:
University of North Carolina at Chapel Hill, Translational & Clinical
Sciences Institute (1UL1TR001111), Duke Translational Medicine
Institute, Duke University, Institute for Clinical and Translational
Science (UL1TR001117), University of California, Irvine, Institute for
Clinical and Translational Research (UL1TR000153), Johns Hopkins
University, Institute for Clinical & Translational Research
(UL1TR001079), The Clinical and Translational Science Institute at
Children's National Center for Translational Science (UL1TR000075),
University of Rochester Clinical and Translational Science Institute
(UL1TR000042), Institute for Clinical and Translational Science at the
University of Iowa (U54TR001013), and Clinical and Translational
Research Institute, University of California, San Diego (UL1TR000100).
NR 0
TC 0
Z9 0
U1 1
U2 4
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 DEC
PY 2015
VL 8
IS 6
BP 623
EP 631
DI 10.1111/cts.12306
PG 9
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA DA3DL
UT WOS:000367676600007
PM 26184433
ER
PT J
AU Begg, MD
Bennett, LM
Cicutto, L
Gadlin, H
Moss, M
Tentler, J
Schoenbaum, E
AF Begg, Melissa D.
Bennett, L. Michelle
Cicutto, Lisa
Gadlin, Howard
Moss, Marc
Tentler, John
Schoenbaum, Ellie
TI Graduate Education for the Future: New Models and Methods for the
Clinical and Translational Workforce
SO CTS-CLINICAL AND TRANSLATIONAL SCIENCE
LA English
DT Article
DE clinical and translational research; education; pipeline; workforce;
career development
ID INTERDISCIPLINARY RESEARCH; TEAM SCIENCE; SCHOLARS; COLLABORATION;
FACULTY; MENTORS; SKILLS
AB This paper is the third in a five-part series on the clinical and translational science educational pipeline, and it focuses on strategies for enhancing graduate research education to improve skills for interdisciplinary team science. Although some of the most cutting edge science takes place at the borders between disciplines, it is widely perceived that advancements in clinical and translational science are hindered by the siloed efforts of researchers who are comfortable working in their separate domains, and reluctant to stray from their own discipline when conducting research. Without appropriate preparation for career success as members and leaders of interdisciplinary teams, talented scientists may choose to remain siloed or to leave careers in clinical and translational science all together, weakening the pipeline and depleting the future biomedical research workforce. To address this threat, it is critical to begin at what is perhaps the most formative moment for academics: graduate training. This paper focuses on designs for graduate education, and contrasts the methods and outcomes from traditional educational approaches with those skills perceived as essential for the workforce of the future, including the capacity for research collaboration that crosses disciplinary boundaries.
C1 [Begg, Melissa D.] Columbia Univ, Off Provost, New York, NY 10027 USA.
[Bennett, L. Michelle] NCI, Ctr Res Strategy, Bethesda, MD 20892 USA.
[Cicutto, Lisa] Univ Colorado, Clin Sci Program, Denver, CO 80202 USA.
[Gadlin, Howard] NIH, Off Ombudsman, Bethesda, MD 20892 USA.
[Moss, Marc] Univ Colorado, Colorado CTSI Educ Training & Career Dev Pillar, Aurora, CO USA.
[Tentler, John] Univ Colorado, Colorado CTSI Educ Training & Career Dev Pillar, Program TL1, Aurora, CO USA.
[Schoenbaum, Ellie] Albert Einstein Coll Med, Clin Res Training Program, Inst Clin & Translat Res, Bronx, NY 10467 USA.
RP Begg, MD (reprint author), Columbia Univ, Off Provost, New York, NY 10027 USA.
EM mdb3@columbia.edu
FU National Center for Advancing Translational Sciences, National
Institutes of Health [UL1 TR000040, UL1 TR001073, UL1 TR001082]
FX This publication was supported in part by the National Center for
Advancing Translational Sciences, National Institutes of Health, through
Grant Numbers UL1 TR000040, UL1 TR001073, and UL1 TR001082.
NR 27
TC 0
Z9 0
U1 2
U2 5
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 DEC
PY 2015
VL 8
IS 6
BP 787
EP 792
DI 10.1111/cts.12359
PG 6
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA DA3DL
UT WOS:000367676600032
PM 26643714
ER
PT J
AU Telford, WG
AF Telford, William G.
TI Near-Ultraviolet Laser Diodes for Brilliant Ultraviolet Fluorophore
Excitation
SO CYTOMETRY PART A
LA English
DT Article
DE flow cytometer; ultraviolet laser; near-ultraviolet laser diode; NUVLD;
brilliant ultraviolet dye
ID HOECHST SIDE POPULATION; FLOW-CYTOMETRY; EXCITED FLUOROCHROMES; VIOLET
AB Although multiple lasers are now standard equipment on most modern flow cytometers, ultraviolet (UV) lasers (325-365 nm) remain an uncommon excitation source for cytometry. Nd:YVO4 frequency-tripled diode pumped solid-state lasers emitting at 355 nm are now the primary means of providing UV excitation on multilaser flow cytometers. Although a number of UV excited fluorochromes are available for flow cytometry, the cost of solid-state UV lasers remains prohibitively high, limiting their use to all but the most sophisticated multilaser instruments. The recent introduction of the brilliant ultraviolet (BUV) series of fluorochromes for cell surface marker detection and their importance in increasing the number of simultaneous parameters for high-dimensional analysis has increased the urgency of including UV sources in cytometer designs; however, these lasers remain expensive. Near-UV laser diodes (NUVLDs), a direct diode laser source emitting in the 370-380 nm range, have been previously validated for flow cytometric analysis of most UV-excited probes, including quantum nanocrystals, the Hoechst dyes, and 4',6-diamidino-2-phenylindole. However, they remain a little-used laser source for cytometry, despite their significantly lower cost. In this study, the ability of NUVLDs to excite the BUV dyes was assessed, along with their compatibility with simultaneous brilliant violet (BV) labeling. A NUVLD emitting at 375 nm was found to excite most of the available BUV dyes at least as well as a UV 355 nm source. This slightly longer wavelength did produce some unwanted excitation of BV dyes, but at sufficiently low levels to require minimal additional compensation. NUVLDs are compact, relatively inexpensive lasers that have higher power levels than the newest generation of small 355 nm lasers. They can, therefore, make a useful, cost-effective substitute for traditional UV lasers in multicolor analysis involving the BUV and BV dyes. Published 2015 Wiley Periodicals, Inc.
C1 [Telford, William G.] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA.
RP Telford, WG (reprint author), NCI, Expt Transplantat & Immunol Branch, NIH, Bldg 10 CRC Room 3-3297 East,10 Ctr Dr, Bethesda, MD 20892 USA.
EM telfordw@mail.nih.gov
NR 16
TC 2
Z9 2
U1 1
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1552-4922
EI 1552-4930
J9 CYTOM PART A
JI Cytom. Part A
PD DEC
PY 2015
VL 87A
IS 12
BP 1127
EP 1137
DI 10.1002/cyto.a.22686
PG 11
WC Biochemical Research Methods; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA DA3BL
UT WOS:000367670800008
PM 25930008
ER
PT J
AU Smith-Trunova, S
Prithviraj, R
Spurrier, J
Kuzina, I
Gu, Q
Giniger, E
AF Smith-Trunova, Svetlana
Prithviraj, Ranjini
Spurrier, Joshua
Kuzina, Irina
Gu, Qun
Giniger, Edward
TI Cdk5 Regulates Developmental Remodeling of Mushroom Body Neurons in
Drosophila
SO DEVELOPMENTAL DYNAMICS
LA English
DT Article
DE axon; dendrite; pruning; microtubules; proteasome; neurodegeneration
ID CYCLIN-DEPENDENT KINASE-5; UBIQUITIN-PROTEASOME SYSTEM; AXON
DEGENERATION; WALLERIAN DEGENERATION; SYNAPTIC PLASTICITY; CENTRAL
BRAIN; IN-VIVO; MECHANISMS; P35; DISTINCT
AB Background: During metamorphosis, axons and dendrites of the mushroom body (MB) in the Drosophila central brain are remodeled extensively to support the transition from larval to adult behaviors. Results: We show here that the neuronal cyclin-dependent kinase, Cdk5, regulates the timing and rate of mushroom body remodeling: reduced Cdk5 activity causes a delay in pruning of MB neurites, while hyperactivation accelerates it. We further show that Cdk5 cooperates with the ubiquitin-proteasome system in this process. Finally, we show that Cdk5 modulates the first overt step in neurite disassembly, dissolution of the neuronal tubulin cytoskeleton, and provide evidence that it also acts at additional steps of MB pruning. Conclusions: These data show that Cdk5 regulates the onset and extent of remodeling of the Drosophila MB. Given the wide phylogenetic conservation of Cdk5, we suggest that it is likely to play a role in developmental remodeling in other systems, as well. Moreover, we speculate that the well-established role of Cdk5 in neurodegeneration may involve some of the same cellular mechanisms that it uses during developmental remodeling. Developmental Dynamics 244:1550-1563, 2015. Published 2015. This article is a U.S. Government work and is in the public domain in the USA
C1 [Smith-Trunova, Svetlana; Prithviraj, Ranjini; Spurrier, Joshua; Kuzina, Irina; Gu, Qun; Giniger, Edward] NINDS, NIH, Bethesda, MD 20892 USA.
[Spurrier, Joshua] Johns Hopkins Univ, NIH, Grad Partnership Program, Bethesda, MD USA.
RP Giniger, E (reprint author), NINDS, NIH, Bldg 35,Room 1C-1002,35 Convent Dr, Bethesda, MD 20892 USA.
EM ginigere@ninds.nih.gov
FU NIH/NINDS [Z01-NS003106]
FX Grant sponsor: NIH/NINDS; Grant number: Z01-NS003106
NR 45
TC 0
Z9 0
U1 2
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1058-8388
EI 1097-0177
J9 DEV DYNAM
JI Dev. Dyn.
PD DEC
PY 2015
VL 244
IS 12
BP 1550
EP 1563
DI 10.1002/DVDY.24350
PG 14
WC Anatomy & Morphology; Developmental Biology
SC Anatomy & Morphology; Developmental Biology
GA DA3FA
UT WOS:000367680900006
PM 26394609
ER
PT J
AU Damiano, D
AF Damiano, Diane
TI Muscle synergies: input or output variables for neural control?
SO DEVELOPMENTAL MEDICINE AND CHILD NEUROLOGY
LA English
DT Editorial Material
ID MOVEMENTS
C1 [Damiano, Diane] NIH, Dept Rehabil Med, Bethesda, MD 20892 USA.
RP Damiano, D (reprint author), NIH, Dept Rehabil Med, Bethesda, MD 20892 USA.
RI Damiano, Diane/B-3338-2010
OI Damiano, Diane/0000-0002-2770-5356
FU Intramural NIH HHS [Z99 CL999999]
NR 7
TC 1
Z9 1
U1 1
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0012-1622
EI 1469-8749
J9 DEV MED CHILD NEUROL
JI Dev. Med. Child Neurol.
PD DEC
PY 2015
VL 57
IS 12
BP 1091
EP 1092
DI 10.1111/dmcn.12843
PG 3
WC Clinical Neurology; Pediatrics
SC Neurosciences & Neurology; Pediatrics
GA DA3GG
UT WOS:000367684600008
PM 26195185
ER
PT J
AU Gadalla, SM
Andreotti, G
AF Gadalla, Shahinaz M.
Andreotti, Gabriella
TI Polychlorinated Biphenyls and Cancer: Are Telomeres to Blame?
SO EBIOMEDICINE
LA English
DT Editorial Material
ID LENGTH
C1 [Gadalla, Shahinaz M.] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Andreotti, Gabriella] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 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
NR 10
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 2352-3964
J9 EBIOMEDICINE
JI EBioMedicine
PD DEC
PY 2015
VL 2
IS 12
BP 1856
EP 1857
DI 10.1016/j.ebiom.2015.12.011
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA DA1EC
UT WOS:000367538100012
PM 26844258
ER
PT J
AU Buckley, AW
Scott, R
Tyler, A
Mahoney, JM
Thurm, A
Farmer, C
Swedo, S
Burroughs, SA
Holmes, GL
AF Buckley, Ashura W.
Scott, Rod
Tyler, Anna
Mahoney, J. Matthew
Thurm, Audrey
Farmer, Cristan
Swedo, Susan
Burroughs, Scott A.
Holmes, Gregory L.
TI State-Dependent Differences in Functional Connectivity in Young Children
With Autism Spectrum Disorder
SO EBIOMEDICINE
LA English
DT Article
DE Epilepsy; Power spectral analysis; Coherence; Pearson; Epileptiform; EEG
ID CORTICAL CONNECTIVITY; WORKING-MEMORY; EEG COHERENCE; BRAIN; SLEEP;
RISK; FMRI; UNDERCONNECTIVITY; ADOLESCENTS; EPILEPSY
AB Background: While there is increasing evidence of altered brain connectivity in autism, the degree and direction of these alterations in connectivity and their uniqueness to autism has not been established. The aim of the present study was to compare connectivity in children with autism to that of typically developing controls and children with developmental delay without autism.
Methods: We assessed EEG spectral power, coherence, phase lag, Pearson and partial correlations, and epileptiform activity during the awake, slow wave sleep, and REM sleep states in 137 children aged 2 to 6 years with autism (n=87), developmental delay without autism (n=21), or typical development (n=29).
Findings: We found that brain connectivity, as measured by coherence, phase lag, and Pearson and partial correlations distinguished children with autism from both neurotypical and developmentally delayed children. In general, children with autism had increased coherence which was most prominent during slow wave sleep.
Interpretation: Functional connectivity is distinctly different in children with autism compared to samples with typical development and developmental delay without autism. Differences in connectivity in autism are state and region related. In this study, children with autism were characterized by a dynamically evolving pattern of altered connectivity. Published by Elsevier B.V.
C1 [Buckley, Ashura W.; Thurm, Audrey; Farmer, Cristan; Swedo, Susan; Holmes, Gregory L.] NIMH, NIH, Bethesda, MD 20892 USA.
[Scott, Rod; Tyler, Anna; Mahoney, J. Matthew; Burroughs, Scott A.] Univ Vermont, Coll Med, Dept Neurol Sci, Burlington, VT 05405 USA.
RP Buckley, AW (reprint author), NIMH, 10 Ctr Dr,Room 1C250, Bethesda, MD 20892 USA.
EM shu.buckley@nih.gov
FU Intramural NIH HHS
NR 55
TC 3
Z9 3
U1 5
U2 8
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 2352-3964
J9 EBIOMEDICINE
JI EBioMedicine
PD DEC
PY 2015
VL 2
IS 12
BP 1905
EP 1915
DI 10.1016/j.ebiom.2015.11.004
PG 11
WC Medicine, General & Internal
SC General & Internal Medicine
GA DA1EC
UT WOS:000367538100023
PM 26844269
ER
PT J
AU Petrovics, G
Li, H
Stumpel, T
Tan, SH
Young, D
Katta, S
Li, QY
Ying, K
Klocke, B
Ravindranath, L
Kohaar, I
Chen, YM
Ribli, D
Grote, K
Zou, H
Cheng, J
Dalgard, CL
Zhang, SM
Csabai, I
Kagan, J
Takeda, D
Loda, M
Srivastava, S
Scherf, M
Seifert, M
Gaiser, T
McLeod, DG
Szallasi, Z
Ebner, R
Werner, T
Sesterhenn, IA
Freedman, M
Dobi, A
Srivastava, S
AF Petrovics, Gyorgy
Li, Hua
Stuempel, Tanja
Tan, Shyh-Han
Young, Denise
Katta, Shilpa
Li, Qiyuan
Ying, Kai
Klocke, Bernward
Ravindranath, Lakshmi
Kohaar, Indu
Chen, Yongmei
Ribli, Dezso
Grote, Korbinian
Zou, Hua
Cheng, Joseph
Dalgard, Clifton L.
Zhang, Shimin
Csabai, Istvan
Kagan, Jacob
Takeda, David
Loda, Massimo
Srivastava, Sudhir
Scherf, Matthias
Seifert, Martin
Gaiser, Timo
McLeod, David G.
Szallasi, Zoltan
Ebner, Reinhard
Werner, Thomas
Sesterhenn, Isabell A.
Freedman, Matthew
Dobi, Albert
Srivastava, Shiv
TI A novel genomic alteration of LSAMP associates with aggressive prostate
cancer in African American men
SO EBIOMEDICINE
LA English
DT Article
DE African American; Prostate cancer; Genome; LSAMP; ERG; PTEN
ID SOMATIC POINT MUTATIONS; ERG ONCOPROTEIN EXPRESSION; GENERATION
SEQUENCING DATA; MOLECULAR DIFFERENCES; WIDE ASSOCIATION; COPY NUMBER;
LANDSCAPE; CELLS; STRATIFICATION; CARCINOGENESIS
AB Evaluation of cancer genomes in global context is of great interest in light of changing ethnic distribution of the world population. We focused our study on men of African ancestry because of their disproportionately higher rate of prostate cancer (CaP) incidence and mortality. We present a systematic whole genome analyses, revealing alterations that differentiate African American (AA) and Caucasian American (CA) CaP genomes. We discovered a recurrent deletion on chromosome 3q13.31 centering on the LSAMP locus that was prevalent in tumors from AA men (cumulative analyses of 435 patients: whole genome sequence, 14; FISH evaluations, 101; and SNP array, 320 patients). Notably, carriers of this deletion experienced more rapid disease progression. In contrast, PTEN and ERG common driver alterations in CaP were significantly lower in AA prostate tumors compared to prostate tumors from CA. Moreover, the frequency of inter-chromosomal rearrangements was significantly higher in AA than CA tumors. These findings reveal differentially distributed somaticmutations in CaP across ancestral groups, which have implications for precision medicine strategies. (C) 2015 The Authors. Published by Elsevier B.V.
C1 [Petrovics, Gyorgy; Li, Hua; Tan, Shyh-Han; Young, Denise; Katta, Shilpa; Ying, Kai; Ravindranath, Lakshmi; Kohaar, Indu; Chen, Yongmei; McLeod, David G.; Dobi, Albert; Srivastava, Shiv] Uniformed Serv Univ Hlth Sci, Dept Surg, Ctr Prostate Dis Res, Bethesda, MD 20814 USA.
[Petrovics, Gyorgy; Li, Hua; Tan, Shyh-Han; Young, Denise; Katta, Shilpa; Ying, Kai; Ravindranath, Lakshmi; Kohaar, Indu; Chen, Yongmei; McLeod, David G.; Dobi, Albert; Srivastava, Shiv] Walter Reed Natl Mil Med Ctr, Bethesda, MD 20814 USA.
[Stuempel, Tanja; Klocke, Bernward; Grote, Korbinian; Scherf, Matthias; Seifert, Martin; Werner, Thomas] Genomatix Software GmbH, D-80335 Munchene, Germany.
[Li, Qiyuan] Xiamen Univ, Coll Med, Xiamen 361102, Peoples R China.
[Li, Qiyuan; Takeda, David; Loda, Massimo; Freedman, Matthew] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02215 USA.
[Ribli, Dezso; Csabai, Istvan] Eotvos Lorand Univ, Dept Phys Complex Syst, H-1117 Budapest, Hungary.
[Ribli, Dezso; Csabai, Istvan; Szallasi, Zoltan] Tech Univ Denmark, Dept Syst Biol, Ctr Biol Sequence Anal, DK-2800 Lyngby, Denmark.
[Zou, Hua; Cheng, Joseph; Ebner, Reinhard] CytoTest Inc, Rockville, MD 20850 USA.
[Dalgard, Clifton L.] Uniformed Serv Univ Hlth Sci, Collaborat Hlth Initiat Res Program, Dept Anat Physiol & Genet, Bethesda, MD 20814 USA.
[Zhang, Shimin; Sesterhenn, Isabell A.] Joint Pathol Ctr, Genitourinary Pathol, Silver Spring, MD 20910 USA.
[Kagan, Jacob; Srivastava, Sudhir] NCI, Canc Biomarkers Res Grp, Canc Prevent Div, Bethesda, MD 20892 USA.
[Takeda, David; Loda, Massimo; Freedman, Matthew] Eli & Edythe L Broad Inst, Cambridge, MA USA.
[Gaiser, Timo] Heidelberg Univ, Med Fak Mannheim, Univ Med Mannheim, Inst Pathol, D-68167 Mannheim, Germany.
[McLeod, David G.] Walter Reed Natl Mil Med Ctr, Urol Serv, Bethesda, MD 20814 USA.
[Szallasi, Zoltan] Harvard Univ, Sch Med, Harvard Mit Div Hlth Sci & Technol, Childrens Hosp Informat Program, Boston, MA 02115 USA.
[Szallasi, Zoltan] Semmelweis Univ, Dept Pathol 2, Hungarian Acad Sci, Brain Metastasis Res Grp,MTA SE NAP, H-1091 Budapest, Hungary.
[Werner, Thomas] Univ Michigan, Div Nephrol, Internal Med, Ann Arbor, MI 48109 USA.
[Werner, Thomas] Univ Michigan, Ctr Computat Med & Bioinformat, Ann Arbor, MI 48109 USA.
RP Freedman, M (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02215 USA.
EM freedman@broadinstitute.org; adobi@cpdr.org; ssrivastava@cpdr.org
OI Tan, Shyh-Han/0000-0001-8250-7005; Csabai, Istvan/0000-0001-9232-9898
FU NCI NIH HHS [R01 CA162383, R01 CA162383-05]
NR 57
TC 7
Z9 7
U1 1
U2 3
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 2352-3964
J9 EBIOMEDICINE
JI EBioMedicine
PD DEC
PY 2015
VL 2
IS 12
BP 1957
EP 1964
DI 10.1016/j.ebiom.2015.10.028
PG 8
WC Medicine, General & Internal
SC General & Internal Medicine
GA DA1EC
UT WOS:000367538100028
PM 26844274
ER
PT J
AU Mazet, JAK
Wei, Q
Zhao, GP
Cummings, DAT
Desmond, JS
Rosenthal, J
King, CH
Cao, WC
Chmura, AA
Hagan, EA
Zhang, SY
Xiao, XM
Xu, JG
Shi, ZL
Feng, F
Liu, XP
Pan, WQ
Zhu, GJ
Zuo, LY
Daszak, P
AF Mazet, Jonna A. K.
Wei, Qin
Zhao, Guoping
Cummings, Derek A. T.
Desmond, James Stephen
Rosenthal, Joshua
King, Charles H.
Cao, Wuchun
Chmura, Aleksei A.
Hagan, Emily A.
Zhang, Shuyi
Xiao, Xiangming
Xu, Jianguo
Shi, Zhengli
Feng, Feng
Liu, Xiuping
Pan, Weiqing
Zhu, Guangjian
Zuo, Liyao
Daszak, Peter
TI Joint China-US Call for Employing a Transdisciplinary Approach to
Emerging Infectious Diseases
SO ECOHEALTH
LA English
DT Editorial Material
ID LAND-USE CHANGE; CLIMATE-CHANGE; EMERGENCE; HEALTH; LANDSCAPES; ECOLOGY
C1 [Mazet, Jonna A. K.] Univ Calif Davis, Sch Vet Med, Hlth Inst 1, Davis, CA 95616 USA.
[Wei, Qin; Feng, Feng; Liu, Xiuping; Zuo, Liyao] Natl Nat Sci Fdn China, Beijing, Peoples R China.
[Zhao, Guoping] Shanghai Inst Biol Sci, Shanghai, Peoples R China.
[Cummings, Derek A. T.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Desmond, James Stephen; Chmura, Aleksei A.; Hagan, Emily A.; Zhu, Guangjian; Daszak, Peter] EcoHlth Alliance, New York, NY USA.
[Rosenthal, Joshua] NIH, Div Epidemiol & Populat Studies, Fogarty Int Ctr, New York, NY USA.
[King, Charles H.] Case Western Reserve Univ, Cleveland, OH 44106 USA.
[Cao, Wuchun] Acad Mil Med Sci, Beijing, Peoples R China.
[Zhang, Shuyi] E China Normal Univ, Shanghai 200062, Peoples R China.
[Xiao, Xiangming] Univ Oklahoma, Norman, OK 73019 USA.
[Xu, Jianguo] Natl Inst Communicable Dis Control & Prevent, Beijing, Peoples R China.
[Shi, Zhengli] Chinese Acad Sci, Wuhan Inst Virol, Wuhan, Peoples R China.
[Pan, Weiqing] Second Mil Med Univ, Shanghai, Peoples R China.
RP Mazet, JAK (reprint author), Univ Calif Davis, Sch Vet Med, Hlth Inst 1, Davis, CA 95616 USA.
EM jkmazet@ucdavis.edu
NR 21
TC 1
Z9 1
U1 0
U2 3
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1612-9202
EI 1612-9210
J9 ECOHEALTH
JI EcoHealth
PD DEC
PY 2015
VL 12
IS 4
BP 555
EP 559
DI 10.1007/s10393-015-1060-1
PG 5
WC Biodiversity Conservation; Ecology; Environmental Sciences
SC Biodiversity & Conservation; Environmental Sciences & Ecology
GA DA2LW
UT WOS:000367627300003
PM 26646835
ER
PT J
AU Schwarzman, MR
Ackerman, JM
Dairkee, SH
Fenton, SE
Johnson, D
Navarro, KM
Osborne, G
Rudel, RA
Solomon, GM
Zeise, L
Janssen, S
AF Schwarzman, Megan R.
Ackerman, Janet M.
Dairkee, Shanaz H.
Fenton, Suzanne E.
Johnson, Dale
Navarro, Kathleen M.
Osborne, Gwendolyn
Rudel, Ruthann A.
Solomon, Gina M.
Zeise, Lauren
Janssen, Sarah
TI Screening for Chemical Contributions to Breast Cancer Risk: A Case Study
for Chemical Safety Evaluation
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Review
ID MAMMARY-GLAND DEVELOPMENT; ESTROGEN-RECEPTOR-ALPHA; IN-UTERO;
PROGESTERONE-RECEPTOR; ENDOCRINE DISRUPTORS; BISPHENOL-A;
2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN TCDD; LACTATIONAL EXPOSURE; TOXCAST
CHEMICALS; GENE-EXPRESSION
AB BACKGROUND: Current approaches to chemical screening, prioritization, and assessment are being reenvisioned, driven by innovations in chemical safety testing, new chemical regulations, and demand for information on human and environmental impacts of chemicals. To conceptualize these changes through the lens of a prevalent disease, the Breast Cancer and Chemicals Policy project convened an interdisciplinary expert panel to investigate methods for identifying chemicals that may increase breast cancer risk.
METHODS: Based on a review of current evidence, the panel identified key biological processes whose perturbation may alter breast cancer risk. We identified corresponding assays to develop the Hazard Identification Approach for Breast Carcinogens (HIA-BC), a method for detecting chemicals that may raise breast cancer risk. Finally, we conducted a literature-based pilot test of the HIA-BC.
RESULTS: The HIA-BC identifies assays capable of detecting alterations to biological processes relevant to breast cancer, including cellular and molecular events, tissue changes, and factors that alter susceptibility. In the pilot test of the HIA-BC, chemicals associated with breast cancer all demonstrated genotoxic or endocrine activity, but not necessarily both. Significant data gaps persist.
CONCLUSIONS: This approach could inform the development of toxicity testing that targets mechanisms relevant to breast cancer, providing a basis for identifying safer chemicals. The study identified important end points not currently evaluated by federal testing programs, including altered mammary gland development, Her2 activation, progesterone receptor activity, prolactin effects, and aspects of estrogen receptor beta activity. This approach could be extended to identify the biological processes and screening methods relevant for other common diseases.
C1 [Schwarzman, Megan R.; Osborne, Gwendolyn] Univ Calif Berkeley, Sch Publ Hlth, Ctr Occupat & Environm Hlth, Berkeley, CA 94720 USA.
[Ackerman, Janet M.; Rudel, Ruthann A.] Silent Spring Inst, Newton, MA USA.
[Dairkee, Shanaz H.] Calif Pacific Med Ctr, Res Inst, San Francisco, CA USA.
[Fenton, Suzanne E.] NIEHS, Div Natl Toxicol Program, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
[Johnson, Dale] Univ Calif Berkeley, Dept Nutr Sci & Toxicol, Berkeley, CA 94720 USA.
[Navarro, Kathleen M.] Univ Calif Berkeley, Dept Environm Hlth, Berkeley, CA 94720 USA.
[Solomon, Gina M.] Calif Environm Protect Agcy, Sacramento, CA USA.
[Zeise, Lauren] Calif Environm Protect Agcy, Off Environm Hlth Hazard Assessment, Sacramento, CA USA.
[Janssen, Sarah] Univ Calif San Francisco, Div Occupat & Environm Med, San Francisco, CA 94143 USA.
[Janssen, Sarah] NRDC, San Francisco, CA USA.
RP Schwarzman, MR (reprint author), 50 Univ Hall,7360, Berkeley, CA 94720 USA.
EM mschwarzman@berkeley.edu
FU California Breast Cancer Research Program; University of California
Office of the President [15QB-8001]; Avon Foundation for Women
FX This work was funded by the California Breast Cancer Research Program,
University of California Office of the President (grant # 15QB-8001),
with partial support for J.M.A. and R.A.R. from a grant from Avon
Foundation for Women.
NR 101
TC 4
Z9 4
U1 6
U2 18
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 DEC
PY 2015
VL 123
IS 12
BP 1255
EP 1264
DI 10.1289/ehp.1408337
PG 10
WC Environmental Sciences; Public, Environmental & Occupational Health;
Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Toxicology
GA DA1WS
UT WOS:000367587000012
PM 26032647
ER
PT J
AU Verner, MA
Loccisano, AE
Morken, NH
Yoon, M
Wu, HL
McDougall, R
Maisonet, M
Marcus, M
Kishi, R
Miyashita, C
Chen, MH
Hsieh, WS
Andersen, ME
Clewell, HJ
Longnecker, MP
AF Verner, Marc-Andre
Loccisano, Anne E.
Morken, Nils-Halvdan
Yoon, Miyoung
Wu, Huali
McDougall, Robin
Maisonet, Mildred
Marcus, Michele
Kishi, Reiko
Miyashita, Chihiro
Chen, Mei-Huei
Hsieh, Wu-Shiun
Andersen, Melvin E.
Clewell, Harvey J., III
Longnecker, Matthew P.
TI Associations of Perfluoroalkyl Substances (PFAS) with Lower Birth
Weight: An Evaluation of Potential Confounding by Glomerular Filtration
Rate Using a Physiologically Based Pharmacokinetic Model (PBPK)
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Article
ID PERFLUOROOCTANOIC ACID EXPOSURE; EVIDENCE-BASED MEDICINE; FETAL-GROWTH;
PERFLUORINATED COMPOUNDS; RENAL HEMODYNAMICS; HUMAN-PREGNANCY; SERUM;
PFOA; CHEMICALS; HEALTH
AB BACKGROUND: Prenatal exposure to perfluoroalkyl substances (PFAS) has been associated with lower birth weight in epidemiologic studies. This association could be attributable to glomerular filtration rate (GFR), which is related to PFAS concentration and birth weight.
OBJECTIVES: We used a physiologically based pharmacokinetic (PBPK) model of pregnancy to assess how much of the PFAS-birth weight association observed in epidemiologic studies might be attributable to GFR.
METHODS: We modified a PBPK model to reflect the association of GFR with birth weight (estimated from three studies of GFR and birth weight) and used it to simulate PFAS concentrations in maternal and cord plasma. The model was run 250,000 times, with variation in parameters, to simulate a population. Simulated data were analyzed to evaluate the association between PFAS levels and birth weight due to GFR. We compared simulated estimates with those from a meta-analysis of epidemiologic data.
RESULTS: The reduction in birth weight for each 1-ng/mL increase in simulated cord plasma for perfluorooctane sulfonate (PFOS) was 2.72g (95% CI: -3.40, -2.04), and for perfluorooctanoic acid (PFOA) was 7.13 g (95% CI: -8.46, -5.80); results based on maternal plasma at term were similar. Results were sensitive to variations in PFAS level distributions and the strength of the GFR-birth weight association. In comparison, our meta-analysis of epidemiologic studies suggested that each 1-ng/mL increase in prenatal PFOS and PFOA levels was associated with 5.00 g (95% CI: -21.66, -7.78) and 14.72 g (95% CI: -8.92, -1.09) reductions in birth weight, respectively.
CONCLUSION: Results of our simulations suggest that a substantial proportion of the association between prenatal PFAS and birth weight may be attributable to confounding by GFR and that confounding by GFR may be more important in studies with sample collection later in pregnancy.
C1 [Verner, Marc-Andre] Harvard Univ, TH Chan Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA.
[Verner, Marc-Andre] Karolinska Inst, Inst Environm Med, S-10401 Stockholm, Sweden.
[Loccisano, Anne E.; Yoon, Miyoung; Wu, Huali; Andersen, Melvin E.; Clewell, Harvey J., III] Hamner Inst Hlth Sci, Ctr Human Hlth Assessment, Res Triangle Pk, NC USA.
[Morken, Nils-Halvdan] Univ Bergen, Dept Global Publ Hlth & Primary Care, Bergen, Norway.
[Morken, Nils-Halvdan] Haukeland Hosp, Dept Obstet & Gynecol, N-5021 Bergen, Norway.
[McDougall, Robin] Aegis Technol, Huntsville, AL USA.
[Maisonet, Mildred] E Tennessee State Univ, Coll Publ Hlth, Biostat & Epidemiol Dept, Johnson City, TN 37614 USA.
[Marcus, Michele] Emory Univ, Rollins Sch Publ Hlth, Dept Epidemiol, Atlanta, GA 30322 USA.
[Kishi, Reiko; Miyashita, Chihiro] Hokkaido Univ, Ctr Environm & Hlth Sci, Sapporo, Hokkaido, Japan.
[Chen, Mei-Huei; Hsieh, Wu-Shiun] Natl Taiwan Univ, Coll Med, Natl Taiwan Univ Hosp, Dept Pediat, Taipei 10764, Taiwan.
[Longnecker, Matthew P.] NIEHS, Epidemiol Branch, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
RP Verner, MA (reprint author), Univ Montreal, Sch Publ Hlth, Dept Occupat & Environm Hlth, 2375 Chemin Cote St Catherine,Suite 4105, Montreal, PQ H3T 1A8, Canada.
EM verner.marcandre@gmail.com
OI Maisonet, Mildred/0000-0003-3561-2632; Yoon,
Miyoung/0000-0002-3653-3488; Longnecker, Matthew/0000-0001-6073-5322
FU DuPont; 3M; Intramural Research Program of the National Institutes of
Environmental Health Sciences (NIEHS), the National Institutes of Health
(NIH)
FX This study was supported by grants from DuPont and 3M, and by the
Intramural Research Program of the National Institutes of Environmental
Health Sciences (NIEHS), the National Institutes of Health (NIH).
NR 47
TC 10
Z9 10
U1 8
U2 24
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 DEC
PY 2015
VL 123
IS 12
BP 1317
EP 1324
DI 10.1289/ehp.1408837
PG 8
WC Environmental Sciences; Public, Environmental & Occupational Health;
Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Toxicology
GA DA1WS
UT WOS:000367587000020
PM 26008903
ER
PT J
AU Neychev, V
Straughan, D
Pacak, K
Kebebew, E
AF Neychev, Vladimir
Straughan, David
Pacak, Karel
Kebebew, Electron
TI Multidisciplinary management of locally advanced and widely metastatic
paraganglioma in a patient with life-threatening compressive symptoms
SO HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND
NECK
LA English
DT Article
DE paraganglioma; succinate dehydrogenase gene (SDHB); metastatic disease;
compressive symptoms; management approach
ID NECK PARAGANGLIOMAS; PHEOCHROMOCYTOMA; HEAD; MUTATIONS; FEATURES; SDHB
AB Background. Patients presenting with locally advanced, metastatic paraganglioma with life-threatening compressive symptoms of critical anatomic structure pose a significant management challenge.
Methods. We present a case of a 15-year-old patient with enlarging right neck mass causing dysphagia and respiratory compromise from near complete obstruction of the oropharynx.
Results. Evaluation of the patient's family history led to the identification of a mutation in the succinate dehydrogenase subunit B (SDSD) gene (G725A). Laboratory and imaging workup revealed an 8.8 x 6.6 x 4.1 cm metabolically and biochemically active right neck mass, a tumor in the left para-aortic region, and multiple bony lesions consistent with widely metastatic disease. Multidisciplinary management included pre-operative clinical optimization, coil embolization, and palliative resection of the neck mass.
Conclusion. Although the currently available treatment options for patients with advanced metastatic paraganglioma render no survival benefit, a multidisciplinary management approach aimed at relief of tumor-related symptoms and catecholamine excess should be undertaken. (C) 2015 Wiley Periodicals, Inc.
C1 [Neychev, Vladimir; Kebebew, Electron] NCI, Endocrine Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Straughan, David] NCI, Thorac & Gastrointestinal Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Pacak, Karel] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrinol & Genet, NIH, Bethesda, MD USA.
RP Kebebew, E (reprint author), Endocrine Oncol Branch EOB, Bldg 10-CRC,Room 4-5952,10 Ctr Dr, Bethesda, MD 20892 USA.
EM kebebewe@mail.nih.gov
FU Intramural Research Program of Center for Cancer Research, National
Cancer Institute
FX Contract grant sponsor: This work was supported in part by the
Intramural Research Program of the Center for Cancer Research, National
Cancer Institute.
NR 12
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1043-3074
EI 1097-0347
J9 HEAD NECK-J SCI SPEC
JI Head Neck-J. Sci. Spec. Head Neck
PD DEC
PY 2015
VL 37
IS 12
BP E205
EP E208
DI 10.1002/hed.24069
PG 4
WC Otorhinolaryngology; Surgery
SC Otorhinolaryngology; Surgery
GA DA3CW
UT WOS:000367674600008
PM 25899001
ER
PT J
AU Lee, YS
Filie, A
Arthur, D
Fojo, AT
Jaffe, ES
AF Lee, Yi-Shan
Filie, Armando
Arthur, Diane
Fojo, Antonio T.
Jaffe, Elaine S.
TI Breast implant-associated anaplastic large cell lymphoma in a patient
with Li-Fraumeni syndrome
SO HISTOPATHOLOGY
LA English
DT Letter
C1 [Lee, Yi-Shan; Filie, Armando; Arthur, Diane; Jaffe, Elaine S.] NCI, Pathol Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
[Fojo, Antonio T.] NCI, Genitourinary Malignancies Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Lee, YS (reprint author), NCI, Pathol Lab, Ctr Canc Res, Bldg 10, Bethesda, MD 20892 USA.
FU Intramural NIH HHS [ZIA SC000550-34]
NR 10
TC 2
Z9 2
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0309-0167
EI 1365-2559
J9 HISTOPATHOLOGY
JI Histopathology
PD DEC
PY 2015
VL 67
IS 6
BP 925
EP 927
DI 10.1111/his.12737
PG 4
WC Cell Biology; Pathology
SC Cell Biology; Pathology
GA DA5CT
UT WOS:000367820500021
PM 25974645
ER
PT J
AU Elshal, MF
Aldahlawi, AM
Saadah, OI
McCoy, JP
AF Elshal, Mohamed F.
Aldahlawi, Alia M.
Saadah, Omar I.
McCoy, J. Philip
TI Reduced Dendritic Cells Expressing CD200R1 in Children with Inflammatory
Bowel Disease: Correlation with Th17 and Regulatory T Cells
SO INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
LA English
DT Article
DE inflammatory bowel disease; ulcerative colitis; Crohn's disease;
plasmacytoid dendritic cells; myeloid dendritic cells; CD200R1; CD200;
TH17 and regulatory T cells
ID ULCERATIVE-COLITIS; CROHNS-DISEASE; ORAL TOLERANCE; PATHOGENESIS;
ACTIVATION; AUTOIMMUNE; RECEPTOR; DIFFERENTIATION; MECHANISMS;
INHIBITION
AB Loss of tolerance of the adaptive immune system towards indigenous flora contributes to the development of inflammatory bowel diseases (IBD). Defects in dendritic cell (DC)-mediated innate and adoptive immune responses are conceivable. The aim of this study was to investigate the expression of the inhibitory molecules CD200R1 and their ligand CD200 on DCs, to clarify the role of the DCs in the pathogenesis of IBD. Thirty-seven pediatric IBD patients (23 with Crohn's disease (CD) and 14 with ulcerative colitis (UC)) with mean age 13.25 +/- 2.9 years were included. Fourteen age-matched healthy pediatric volunteers (five males and nine females) served as a control group (HC). The percentage of CD11c(+) myeloid dendritic cells (mDCs) and CD123(+) plasmacytoid DCs (pDCs) expressing CD200R1 and CD200 were evaluated in peripheral blood using flow cytometry and were correlated with routine biochemical, serological markers, serum levels of cytokines and with the percentages of circulating regulatory T cells (Treg) and CD4(+) producing IL-17 (Th17). IBD patients showed a significant decrease in the percentage of pDCs and mDCs expressing CD200R1 compared to that of HC. Patients with UC showed increased expressions of the CD200 molecule on pDCs as compared to HC. DCs expressing CD200R1 were found to be correlated positively with Treg and negatively with TH17 and erythrocyte sedimentation rate (ESR). Our findings suggest that IBD is associated with dysregulation in the CD200R1/CD200 axis and that the decrease in DCs expressing CD200R1 may contribute to the imbalance of Th17 and Treg cells and in the pathogenesis of IBD.
C1 [Elshal, Mohamed F.] King Abdulaziz Univ, Fac Sci, Dept Biochem, Jeddah 21589, Saudi Arabia.
[Elshal, Mohamed F.; Aldahlawi, Alia M.; Saadah, Omar I.; McCoy, J. Philip] King Abdulaziz Univ, Inflammatory Bowel Dis Res Grp, Jeddah 21589, Saudi Arabia.
[Elshal, Mohamed F.] Sadat City Univ, Dept Mol Biol, Genet Engn & Biotechnol Res Inst, Sadat City 32897, Egypt.
[Aldahlawi, Alia M.] King Abdulaziz Univ, Dept Biol Sci, Fac Sci, Jeddah 21589, Saudi Arabia.
[Aldahlawi, Alia M.] King Abdulaziz Univ, Immunol Unit, King Fahd Med Res Ctr, Jeddah 21589, Saudi Arabia.
[Saadah, Omar I.] King Abdulaziz Univ, Dept Pediat, Fac Med, Jeddah 21589, Saudi Arabia.
[McCoy, J. Philip] NHLBI, Flow Cytometry Core Facil, NIH, Bethesda, MD 20892 USA.
RP Elshal, MF (reprint author), King Abdulaziz Univ, Fac Sci, Dept Biochem, Jeddah 21589, Saudi Arabia.
EM melshal@kau.edu.sa; alia008@hotmail.com; osaadah@kau.edu.sa;
mccoyj@nhlbi.nih.gov
RI Genetic Engineering & Biotechnology, Research Institute /E-7221-2017;
Faculty of, Sciences, KAU/E-7305-2017; Fac Sci, KAU, Biol Sci
Dept/L-4228-2013
FU Deanship of Scientific Research at King Abdulaziz University, Jeddah,
Saudi Arabia [RG/32/02]
FX The authors would like to express their sincere appreciation to the
Deanship of Scientific Research at the King Abdulaziz University,
Jeddah, Saudi Arabia, for funding this Research Group Project No.
RG/32/02.
NR 51
TC 1
Z9 1
U1 0
U2 2
PU MDPI AG
PI BASEL
PA POSTFACH, CH-4005 BASEL, SWITZERLAND
SN 1422-0067
J9 INT J MOL SCI
JI Int. J. Mol. Sci.
PD DEC
PY 2015
VL 16
IS 12
BP 28998
EP 29010
DI 10.3390/ijms161226143
PG 13
WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary
SC Biochemistry & Molecular Biology; Chemistry
GA DA1DD
UT WOS:000367535600064
PM 26690123
ER
PT J
AU O'Donohoe, PK
Taylor, JG
AF O'Donohoe, P. K.
Taylor, J. G.
TI MICRO RNA EXPRESSION AND VASO-OCCLUSIVE PAIN CRISES IN SICKLE CELL
ANAEMIA
SO IRISH JOURNAL OF MEDICAL SCIENCE
LA English
DT Meeting Abstract
C1 [O'Donohoe, P. K.] Natl Univ Ireland Univ Coll Dublin, UCD Sch Med, Dublin 4, Ireland.
[Taylor, J. G.] NHLBI, Bethesda, MD 20892 USA.
NR 2
TC 0
Z9 0
U1 1
U2 1
PU SPRINGER LONDON LTD
PI LONDON
PA 236 GRAYS INN RD, 6TH FLOOR, LONDON WC1X 8HL, ENGLAND
SN 0021-1265
EI 1863-4362
J9 IRISH J MED SCI
JI Irish J. Med. Sci.
PD DEC
PY 2015
VL 184
SU 12
MA 10
BP 554
EP 555
PG 2
WC Medicine, General & Internal
SC General & Internal Medicine
GA DA5LA
UT WOS:000367843400011
ER
PT J
AU Hasin, DS
Saha, TD
Kerridge, BT
Goldstein, RB
Chou, SP
Zhang, HT
Jung, J
Pickering, RP
Ruan, WJ
Smith, SM
Huang, BJ
Grant, BF
AF Hasin, Deborah S.
Saha, Tulshi D.
Kerridge, Bradley T.
Goldstein, Rise B.
Chou, S. Patricia
Zhang, Haitao
Jung, Jeesun
Pickering, Roger P.
Ruan, W. June
Smith, Sharon M.
Huang, Boji
Grant, Bridget F.
TI Prevalence of Marijuana Use Disorders in the United States Between
2001-2002 and 2012-2013
SO JAMA PSYCHIATRY
LA English
DT Article
ID ALCOHOL-USE DISORDER; NATIONAL EPIDEMIOLOGIC SURVEY; INTERVIEW SCHEDULE
AUDADIS; GENERAL-POPULATION SAMPLE; SUBSTANCE USE DISORDERS; CANNABIS
CONTROL POLICY; SOCIAL STRESS MODEL; DRUG-USE DISORDERS;
QUALITY-OF-LIFE; DSM-IV ALCOHOL
AB IMPORTANCE Laws and attitudes toward marijuana in the United States are becoming more permissive but little is known about whether the prevalence rates of marijuana use and marijuana use disorders have changed in the 21st century.
OBJECTIVE To present nationally representative information on the past-year prevalence rates of marijuana use, marijuana use disorder, and marijuana use disorder among marijuana users in the US adult general population and whether this has changed between 2001-2002 and 2012-2013.
DESIGN, SETTING, AND PARTICIPANTS Face-to-face interviews conducted in surveys of 2 nationally representative samples of US adults: the National Epidemiologic Survey on Alcohol and Related Conditions (data collected April 2001-April 2002; N = 43 093) and the National Epidemiologic Survey on Alcohol and Related Conditions-III (data collected April 2012-June 2013; N = 36 309). Data were analyzed March through May 2015.
MAIN OUTCOMES AND MEASURES Past-year marijuana use and DSM-IV marijuana use disorder (abuse or dependence).
RESULTS The past-year prevalence of marijuana use was 4.1% (SE, 0.15) in 2001-2002 and 9.5% (SE, 0.27) in 2012-2013, a significant increase (P < .05). Significant increases were also found across demographic subgroups (sex, age, race/ethnicity, education, marital status, income, urban/rural, and region). The past-year prevalence of DSM-IV marijuana use disorder was 1.5% (0.08) in 2001-2002 and 2.9% (SE, 0.13) in 2012-2013 (P < .05). With few exceptions, increases in the prevalence of marijuana use disorder between 2001-2002 and 2012-2013 were also statistically significant (P < .05) across demographic subgroups. However, the prevalence of marijuana use disorder among marijuana users decreased significantly from 2001-2002 (35.6%; SE, 1.37) to 2012-2013 (30.6%; SE, 1.04).
CONCLUSIONS AND RELEVANCE The prevalence of marijuana use more than doubled between 2001-2002 and 2012-2013, and there was a large increase in marijuana use disorders during that time. While not all marijuana users experience problems, nearly 3 of 10 marijuana users manifested a marijuana use disorder in 2012-2013. Because the risk for marijuana use disorder did not increase among users, the increase in prevalence of marijuana use disorder is owing to an increase in prevalence of users in the US adult population. Given changing laws and attitudes toward marijuana, a balanced presentation of the likelihood of adverse consequences of marijuana use to policy makers, professionals, and the public is needed.
C1 [Hasin, Deborah S.] Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY USA.
[Hasin, Deborah S.] Columbia Univ, Mailman Sch Publ Hlth, New York, NY USA.
[Hasin, Deborah S.] New York State Psychiat Inst & Hosp, New York, NY 10032 USA.
[Saha, Tulshi D.; Goldstein, Rise B.; Chou, S. Patricia; Zhang, Haitao; Jung, Jeesun; Pickering, Roger P.; Ruan, W. June; Smith, Sharon M.; Huang, Boji; Grant, Bridget F.] NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH, Rockville, MD 20852 USA.
[Kerridge, Bradley T.] Columbia Univ, Dept Epidemiol, Mailman Sch Publ Hlth, New York, NY USA.
RP Grant, BF (reprint author), NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH, 5635 Fishers Ln,Room 3077, Rockville, MD 20852 USA.
EM bgrant@mail.nih.gov
OI Goldstein, Rise/0000-0002-9603-9473
FU National Institute on Alcohol Abuse and Alcoholism; National Institute
on Drug Abuse [R01DA034244-01, F32DA0364431]; New York State Psychiatric
Institute; intramural program, National Institute on Alcohol Abuse and
Alcoholism, National Institutes of Health
FX The National Epidemiologic Survey on Alcohol and Related Conditions-III
was sponsored by the National Institute on Alcohol Abuse and Alcoholism,
with supplemental support from the National Institute on Drug Abuse.
Support for this study was received from National Institute on Drug
Abuse grant R01DA034244-01 and New York State Psychiatric Institute (Dr
Hasin); National Institute on Drug Abuse grant F32DA0364431 (Dr
Kerridge); and the intramural program, National Institute on Alcohol
Abuse and Alcoholism, National Institutes of Health.
NR 88
TC 49
Z9 49
U1 8
U2 24
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 DEC
PY 2015
VL 72
IS 12
BP 1235
EP 1242
DI 10.1001/jamapsychiatry.2015.1858
PG 8
WC Psychiatry
SC Psychiatry
GA DA1UY
UT WOS:000367582200016
PM 26502112
ER
PT J
AU Jha, S
Wang, Z
Laucis, N
Bhattacharyya, T
AF Jha, Smita
Wang, Zhong
Laucis, Nicholas
Bhattacharyya, Timothy
TI Trends in Media Reports, Oral Bisphosphonate Prescriptions, and Hip
Fractures 1996-2012: An Ecological Analysis
SO JOURNAL OF BONE AND MINERAL RESEARCH
LA English
DT Article
DE OSTEOPOROSIS; FRACTURE PREVENTION; ANTIRESORPTIVES; GENERAL POPULATION
STUDIES; EPIDEMIOLOGY; BISPHOSPHONATE
ID FEMORAL-SHAFT FRACTURES; MINERAL-RESEARCH; UNITED-STATES; OSTEOPOROSIS;
RISK; BENEFITS; COVERAGE; CANADA; CANCER; RATES
AB Bisphosphonates are effective for the treatment of osteoporosis despite recent reports of safety concerns such as atypical femur fracture. We conducted an ecological analysis of relevant media reports, oral bisphosphonate use, and fracture outcomes in the United States. Trends in media reports and public interest of bisphosphonates were quantified using data from Google Trends. Data from the Medical Expenditure Panel Survey (MEPS) and the National Inpatient Sample (NIS) were used to estimate the trends in oral bisphosphonate use among patients aged 55 years and older and hospitalizations for intertrochanteric and subtrochanteric fractures, respectively. These trends in the prevalence of oral bisphosphonate use and the age-adjusted incidence rate of intertrochanteric and subtrochanteric fractures were examined from 1996 to 2012. A series of spikes in Internet search activity for alendronate (Fosamax) occurred between 2006 and 2010 immediately following media reports of safety concerns. Oral bisphosphonate use declined by greater than 50% between 2008 and 2012 (p < 0.001) after increasing use for more than a decade. The decline was more common in patients with lower education levels. Intertrochanteric hip fractures declined from 1996 through 2006 (p < 0.001) and continued to decline from 2008 to 2012 (p < 0.05). Subtrochanteric and diaphyseal fractures showed a steady and significant increase from 2002 to 2011 (p < 0.05). However, the incidence decreased from a peak of 30.5 per 100,000 in 2011 to 26.7 per 100,000 in 2012. The plateauing and subsequent decline in oral bisphosphonate use since 2006 coincided with reports of safety concerns of bisphosphonates, despite the fact that U.S. Food and Drug Administration (FDA) and American Society of Bone and Mineral Research (ASBMR) reports did not recommend any safety restrictions on their use. This decline in oral bisphosphonate use was followed by the decline in the incidence of subtrochanteric and diaphyseal fractures. (C) 2015 American Society for Bone and Mineral Research.
C1 [Jha, Smita] Natl Inst Child Hlth & Human Dev NICHD, NIH, Bethesda, MD USA.
[Wang, Zhong; Laucis, Nicholas] Natl Inst Arthrit & Musculoskeletal & Skin Dis NI, Clin & Investigat Orthoped Surg, Intramural Res Program, NIH, Bethesda, MD USA.
[Bhattacharyya, Timothy] Natl Inst Arthrit & Musculoskeletal & Skin Dis NI, NIH, Bethesda, MD USA.
RP Bhattacharyya, T (reprint author), NIAMS, NIH, 1 AMS Circle, Bethesda, MD 20892 USA.
EM timothy.bhattacharyya@nih.gov
FU National Institute of Arthritis and Musculoskeletal and Skin Diseases
(NIAMS) of the National Institutes of Health (NIH)
FX This research was supported by the Intramural Research Program of the
National Institute of Arthritis and Musculoskeletal and Skin Diseases
(NIAMS) of the National Institutes of Health (NIH).
NR 31
TC 15
Z9 15
U1 0
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0884-0431
EI 1523-4681
J9 J BONE MINER RES
JI J. Bone Miner. Res.
PD DEC
PY 2015
VL 30
IS 12
BP 2179
EP 2187
DI 10.1002/jbmr.2565
PG 9
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA DA3JD
UT WOS:000367692100006
PM 26018247
ER
PT J
AU Forcina, GC
Castro, A
Bokesch, HR
Spakowicz, DJ
Legaspi, ME
Kucera, K
Villota, S
Narvaez-Trujillo, A
McMahon, JB
Gustafson, KR
Strobelt, SA
AF Forcina, Giovanni C.
Castro, Amaya
Bokesch, Heidi R.
Spakowicz, Daniel J.
Legaspi, Michelle E.
Kucera, Kaury
Villota, Stephany
Narvaez-Trujillo, Alexandra
McMahon, James B.
Gustafson, Kirk R.
Strobelt, Scott A.
TI Stelliosphaerols A and B, Sesquiterpene-Polyol Conjugates from an
Ecuadorian Fungal Endophyte
SO JOURNAL OF NATURAL PRODUCTS
LA English
DT Article
ID NATURAL-PRODUCTS; DRUG DISCOVERY; LARGE PHYLOGENIES; MODELS; TOOL
AB Endophytic fungi are plant tissue-associated fungi that represent a rich resource of unexplored biological and chemical diversity. As part of an ongoing effort to characterize Amazon rainforest-derived endophytes, numerous fungi were isolated and cultured from plants collected in the Yasuni National Park in Ecuador. Of these samples, phylogenetic and morphological data revealed a previously undescribed fungus in the order Pleosporales that was cultured from the tropical tree Duroia hirsuta. Extracts from this fungal isolate displayed activity against Staphylococcus aureus and were thus subjected to detailed chemical studies. Two compounds with modest antibacterial activity were isolated, and their structures were elucidated using a combination of NMR spectroscopic analysis, LC-MS studies, and chemical degradation. These efforts led to the identification of stelliosphaerols A (1) and B (2), new sesquiterpene-polyol conjugates that are responsible, at least in part, for the S. aureus inhibitory activity of the fungal extract.
C1 [Forcina, Giovanni C.; Spakowicz, Daniel J.; Legaspi, Michelle E.; Kucera, Kaury; Strobelt, Scott A.] Yale Univ, Dept Mol Biophys & Biochem, New Haven, CT 06520 USA.
[Castro, Amaya; Bokesch, Heidi R.; McMahon, James B.; Gustafson, Kirk R.] Natl Canc Inst, Ctr Canc Res, Mol Targets Lab, Frederick, MD 21702 USA.
[Bokesch, Heidi R.] Leidos Biomed Res Inc, Frederick Natl Lab, Basic Sci Program, Frederick, MD 21702 USA.
[Villota, Stephany; Narvaez-Trujillo, Alexandra] Pontificia Univ Catolica Ecuador, Lab Biotecnol Vegetal, Quito 17012184, Ecuador.
RP Gustafson, KR (reprint author), Natl Canc Inst, Ctr Canc Res, Mol Targets Lab, Frederick, MD 21702 USA.
EM gustafki@mail.nih.gov; strobel@yale.edu
FU HHMI Professorship; NSF [OISE 853408]; Intramural Research Program of
the NIH, National Cancer Institute, Center for Cancer Research; Federal
funds from the National Cancer Institute, National Institutes of Health
[HHSN261200800001E]
FX We thank the Ministerio del Ambiente of Ecuador for a collecting and
research permit provided to S.A.S. We thank P. Vargus Nunez for help
with host plant identification, D. Spakowicz for guidance with
phylogenetic analysis, the Endophyte Collection Quito Catolica (CEQCA)
for cataloging the microbial isolates, and S. Tarasov and M. Dyba
(Biophysics Resource Core, Structural Biophysics Laboratory, CCR) for
assistance with high-resolution mass spectrometry. This research was
funded in part by an HHMI Professorship and NSF grant OISE 853408
awarded to S.A.S. It was also supported by the Intramural Research
Program of the NIH, National Cancer Institute, Center for Cancer
Research, and with Federal funds from the National Cancer Institute,
National Institutes of Health, under contract HHSN261200800001E. The
content of this publication does not necessarily reflect the views or
policies of the Department of Health and Human Services, nor does
mention of trade names, commercial products, or organizations imply
endorsement by the U.S. Government.
NR 20
TC 0
Z9 0
U1 6
U2 11
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 DEC
PY 2015
VL 78
IS 12
BP 3005
EP 3010
DI 10.1021/acs.jnatprod.5b00749
PG 6
WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy
SC Plant Sciences; Pharmacology & Pharmacy
GA DA1NN
UT WOS:000367562600017
PM 26651879
ER
PT J
AU Talegawkar, SA
Tanaka, T
Maras, JE
Ferrucci, L
Tucker, KL
AF Talegawkar, S. A.
Tanaka, T.
Maras, J. E.
Ferrucci, L.
Tucker, K. L.
TI Validation of nutrient intake estimates derived using a
semi-quantitative FFQ against 3 day diet records in the Baltimore
Longitudinal Study of Aging
SO JOURNAL OF NUTRITION HEALTH & AGING
LA English
DT Article
DE Food frequency questionnaire; diet records; validation; Baltimore
Longitudinal Study of Aging
ID FOOD FREQUENCY QUESTIONNAIRE; BODY-MASS INDEX; HISPANIC ADULTS;
OLDER-ADULTS; VALIDITY; WOMEN; REPRODUCIBILITY; PATTERNS; FAT; MEN
AB Objective: To examine the relative validity of a multicultural FFQ used to derive nutrient intake estimates in a community dwelling cohort of younger and older men and women compared with those derived from 3 day (3d) diet records during the same time-frame. Design: Cross-sectional analyses. Setting: The Baltimore Longitudinal Study of Aging (BLSA) conducted in the Baltimore, MD and District of Columbia areas. Participants: A subset (n=468, aged 26 to 95 years (y), 47% female, 65% non-Hispanic white) from the BLSA, with complete data for nutrient estimates from a FFQ and 3d diet records. Measurements: Pearson's correlation coefficients (energy adjusted and de-attenuated) for intakes of energy and 26 nutrients estimated from the FFQ and the mean of 3d diet records were calculated in a cross-sectional analysis. Rankings of individuals based on FFQ for various nutrient intakes were compared to corresponding rankings based on the average of the 3d diet records. Bland Altman plots were examined for a visual representation of agreement between both assessment methods. All analyses were stratified by sex and age (above and below 65 y). Results: Median nutrient intake estimates tended to be higher from the FFQ compared to average 3d diet records. Energy adjusted and de-attenuated correlations between FFQ intake estimates and records ranged from 0.23 (sodium intake in men) to 0.81 (alcohol intake in women). The FFQ classified more than 70 percent of participants in either the same or adjacent quartile categories for all nutrients examined. Bland Altman plots demonstrated good agreement between the assessment methods for most nutrients. Conclusions: This FFQ provides reasonably valid estimates of dietary intakes of younger and older participants of the BLSA.
C1 [Talegawkar, S. A.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA.
[Tanaka, T.; Ferrucci, L.] NIA, Baltimore, MD 21224 USA.
[Maras, J. E.] Northeastern Univ, Dept Hlth Sci, Boston, MA 02115 USA.
[Tucker, K. L.] Univ Massachusetts, Coll Hlth Sci, Dept Clin Lab & Nutr Sci, Lowell, MA USA.
RP Talegawkar, SA (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA.
EM sameera.talegawkar@alumni.tufts.edu
NR 42
TC 1
Z9 1
U1 3
U2 6
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 DEC
PY 2015
VL 19
IS 10
BP 994
EP 1002
DI 10.1007/s12603-015-0659-9
PG 9
WC Geriatrics & Gerontology; Nutrition & Dietetics
SC Geriatrics & Gerontology; Nutrition & Dietetics
GA DA3KU
UT WOS:000367696400005
PM 26624210
ER
PT J
AU Desai, CS
Ning, HY
Liu, K
Reis, JP
Gidding, SS
Armstrong, A
Lima, JAC
Lloyd-Jones, DM
AF Desai, Chintan S.
Ning, Hongyan
Liu, Kiang
Reis, Jared P.
Gidding, Samuel S.
Armstrong, Anderson
Lima, Joao A. C.
Lloyd-Jones, Donald M.
TI Cardiovascular Health in Young Adulthood and Association with Left
Ventricular Structure and Function Later in Life: The Coronary Artery
Risk Development in Young Adults Study
SO JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY
LA English
DT Article
DE Echocardiography; Cardiovascular health; Left ventricular mass
ID DIASTOLIC DYSFUNCTION; CARDIA; MASS; ECHOCARDIOGRAPHY; RECOMMENDATIONS;
HYPERTENSION; PREVALENCE; COMMUNITY; GEOMETRY; BEHAVIOR
AB Background: The aim of this study was to determine the association between cardiovascular health (CVH) in young adulthood and left ventricular (LV) structure and function later in life.
Methods: Participants from the Coronary Artery Risk Development in Young Adults study, which recruited black and white participants aged 18 to 30 years at baseline, were included; echocardiography was performed at year 25. CVH at year 0 was defined on the basis of blood pressure, total cholesterol, fasting glucose, body mass index, smoking status, diet, and physical activity. Two, 1, or 0 points were assigned to each component for ideal, intermediate, and poor levels of each component. Participants were stratified into CVH groups on the basis of point score: <= 8 (poor), 9 to 11 (intermediate), and 12 to 14 (ideal).
Results: The distribution of CVH at year 0 was as follows: poor, n = 264 (9%); intermediate, n = 1,315 (47%); and ideal, n = 1,224 (44%). Individuals with ideal and intermediate CVH at year 0 had significantly lower LV end-diastolic volume and lower LV mass index at year 25. In participants with ideal and intermediate CVH, the multivariate-adjusted odds ratios for diastolic dysfunction at year 25 was 0.52 (95% CI, 0.37-0.73) and 0.63 (95% CI, 0.46-0.83), respectively, compared with participants with poor CVH. Participants with ideal and intermediate CVH had significantly lower odds for LV hypertrophy; the LV mass index was 5.3 to 8.7 g/m(2.7) lower (P <.001 for both) than in participants with poor CVH.
Conclusion: Greater levels of CVH in young adulthood are associated with lower LV mass and lower risk for diastolic dysfunction 25 years later. (J Am Soc Echocardiogr 2015; 28: 1452-61.)
C1 [Desai, Chintan S.; Armstrong, Anderson; Lima, Joao A. C.] Johns Hopkins Univ Hosp, Div Cardiol, Baltimore, MD 21287 USA.
[Ning, Hongyan; Liu, Kiang; Lloyd-Jones, Donald M.] Northwestern Univ, Dept Prevent Med, Feinberg Sch Med, Chicago, IL 60611 USA.
[Reis, Jared P.] NHLBI, Bethesda, MD 20892 USA.
[Gidding, Samuel S.] Thomas Jefferson Med Ctr, Philadelphia, PA USA.
RP Lloyd-Jones, DM (reprint author), Northwestern Univ, Clin & Translat Sci Inst, Feinberg Sch Med, 680 N Lake Shore Dr,Suite 1400, Chicago, IL 60611 USA.
EM dlj@northwestern.edu
FU National Heart, Lung, and Blood Institute [N01-HC95095, N01-HC48047];
University of Minnesota [N01-HC48048]; Northwestern University
[N01-HC48049]; Kaiser Foundation Research Institute [N01-HC48050];
National Institutes of Health [T32 HL 69771-8]
FX The Coronary Artery Risk Development in Young Adults study was conducted
and supported by the National Heart, Lung, and Blood Institute in
collaboration with the University of Alabama at Birmingham (grants
N01-HC95095 and N01-HC48047), the University of Minnesota (grant
N01-HC48048), Northwestern University (grant N01-HC48049), and the
Kaiser Foundation Research Institute (grant N01-HC48050). Dr Desai was
supported by National Institutes of Health grant T32 HL 69771-8.
NR 27
TC 3
Z9 3
U1 1
U2 3
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0894-7317
J9 J AM SOC ECHOCARDIOG
JI J. Am. Soc. Echocardiogr.
PD DEC
PY 2015
VL 28
IS 12
BP 1452
EP 1461
DI 10.1016/j.echo.2015.07.026
PG 10
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA DA3DV
UT WOS:000367677700012
PM 26341123
ER
PT J
AU Okada, T
Linguraru, MG
Hori, M
Summers, RM
Tomiyama, N
Sato, Y
AF Okada, Toshiyuki
Linguraru, Marius George
Hori, Masatoshi
Summers, Ronald M.
Tomiyama, Noriyuki
Sato, Yoshinobu
TI Abdominal multi-organ segmentation from CT images using conditional
shape-location and unsupervised intensity priors
SO MEDICAL IMAGE ANALYSIS
LA English
DT Article
DE Subject-specific priors; Partial least squares regression; Computational
anatomy; Statistical shape model; Probabilistic atlas
ID AUTOMATIC LIVER SEGMENTATION; PROBABILISTIC ATLAS; COMPUTED-TOMOGRAPHY;
MODEL; REGRESSION; AORTA; CUT
AB This paper addresses the automated segmentation of multiple organs in upper abdominal computed tomography (CT) data. The aim of our study is to develop methods to effectively construct the conditional priors and use their prediction power for more accurate segmentation as well as easy adaptation to various imaging conditions in CT images, as observed in clinical practice. We propose a general framework of multi-organ segmentation which effectively incorporates interrelations among multiple organs and easily adapts to various imaging conditions without the need for supervised intensity information. The features of the framework are as follows: (1) A method for modeling conditional shape and location (shape-location) priors, which we call prediction-based priors, is developed to derive accurate priors specific to each subject, which enables the estimation of intensity priors without the need for supervised intensity information. (2) Organ correlation graph is introduced, which defines how the conditional priors are constructed and segmentation processes of multiple organs are executed. In our framework, predictor organs, whose segmentation is sufficiently accurate by using conventional single-organ segmentation methods, are pre-segmented, and the remaining organs are hierarchically segmented using conditional shape-location priors. The proposed framework was evaluated through the segmentation of eight abdominal organs (liver, spleen, left and right kidneys, pancreas, gallbladder, aorta, and inferior vena cava) from 134 CT data from 86 patients obtained under six imaging conditions at two hospitals. The experimental results show the effectiveness of the proposed prediction-based priors and the applicability to various imaging conditions without the need for supervised intensity information. Average Dice coefficients for the liver, spleen, and kidneys were more than 92%, and were around 73% and 67% for the pancreas and gallbladder, respectively. (C) 2015 Elsevier B.V. All rights reserved.
C1 [Okada, Toshiyuki] Univ Tsukuba, Fac Med, Dept Surg, Tsukuba, Ibaraki 3058575, Japan.
[Linguraru, Marius George] Childrens Natl Med Ctr, Sheikh Zayed Inst Pediat Surg Innovat, Washington, DC 20010 USA.
[Linguraru, Marius George] George Washington Univ, Sch Med & Hlth Sci, Dept Radiol, Washington, DC 20037 USA.
[Linguraru, Marius George] George Washington Univ, Sch Med & Hlth Sci, Dept Pediat, Washington, DC 20037 USA.
[Hori, Masatoshi; Tomiyama, Noriyuki] Osaka Univ, Grad Sch Med, Dept Radiol, Suita, Osaka 5650871, Japan.
[Summers, Ronald M.] NIH, Ctr Clin, Radiol & Imaging Sci, Bethesda, MD 20892 USA.
[Sato, Yoshinobu] Nara Inst Sci & Technol, Grad Sch Informat Sci, Ikoma, Nara 6300192, Japan.
RP Sato, Y (reprint author), Nara Inst Sci & Technol, Grad Sch Informat Sci, 8916-5 Takayama Cho, Ikoma, Nara 6300192, Japan.
EM yoshi@is.naist.jp
OI Hori, Masatoshi/0000-0002-2523-3789
FU MEXT/JSPS [21103003, 26108004]; Intramural Research Program of the
National Institutes of Health, Clinical Center
FX This work was partly supported by MEXT/JSPS Grand-in-Aid for Scientific
Research on Innovative Areas No. 21103003 and No. 26108004, and the
Intramural Research Program of the National Institutes of Health,
Clinical Center, and a philanthropic gift from the Government of Abu
Dhabi to Children's National Medical Center.
NR 59
TC 13
Z9 14
U1 4
U2 8
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1361-8415
EI 1361-8423
J9 MED IMAGE ANAL
JI Med. Image Anal.
PD DEC
PY 2015
VL 26
IS 1
BP 1
EP 18
DI 10.1016/j.media.2015.06.009
PG 18
WC Computer Science, Artificial Intelligence; Computer Science,
Interdisciplinary Applications; Engineering, Biomedical; Radiology,
Nuclear Medicine & Medical Imaging
SC Computer Science; Engineering; Radiology, Nuclear Medicine & Medical
Imaging
GA DA0MI
UT WOS:000367490800001
PM 26277022
ER
PT J
AU Albright, RA
Stabach, P
Cao, WX
Kavanagh, D
Mullen, I
Braddock, AA
Covo, MS
Tehan, M
Yang, GX
Cheng, ZL
Bouchard, K
Yu, ZX
Thorn, S
Wang, XN
Folta-Stogniew, EJ
Negrete, A
Sinusas, AJ
Shiloach, J
Zubal, G
Madri, JA
De La Cruz, EM
Braddock, DT
AF Albright, Ronald A.
Stabach, Paul
Cao, Wenxiang
Kavanagh, Dillon
Mullen, Isabelle
Braddock, Alexander A.
Covo, Mariel S.
Tehan, Martin
Yang, Guangxiao
Cheng, Zhiliang
Bouchard, Keith
Yu, Zhao-Xue
Thorn, Stephanie
Wang, Xiangning
Folta-Stogniew, Ewa J.
Negrete, Alejandro
Sinusas, Albert J.
Shiloach, Joseph
Zubal, George
Madri, Joseph A.
De La Cruz, Enrique M.
Braddock, Demetrios T.
TI ENPP1-Fc prevents mortality and vascular calcifications in rodent model
of generalized arterial calcification of infancy
SO NATURE COMMUNICATIONS
LA English
DT Article
ID PSEUDOXANTHOMA ELASTICUM; ECTOPIC MINERALIZATION; LIGHT-SCATTERING;
PYROPHOSPHATE; MUTATIONS; ABCC6; MICE; PRESENTATIONS; DEFICIENCY;
FAILURE
AB Diseases of ectopic calcification of the vascular wall range from lethal orphan diseases such as generalized arterial calcification of infancy (GACI), to common diseases such as hardening of the arteries associated with aging and calciphylaxis of chronic kidney disease (CKD). GACI is a lethal orphan disease in which infants calcify the internal elastic lamina of their medium and large arteries and expire of cardiac failure as neonates, while calciphylaxis of CKD is a ubiquitous vascular calcification in patients with renal failure. Both disorders are characterized by vascular Monckeburg's sclerosis accompanied by decreased concentrations of plasma inorganic pyrophosphate (PPi). Here we demonstrate that subcutaneous administration of an ENPP1-Fc fusion protein prevents the mortality, vascular calcifications and sequela of disease in animal models of GACI, and is accompanied by a complete clinical and biomarker response. Our findings have implications for the treatment of rare and common diseases of ectopic vascular calcification.
C1 [Albright, Ronald A.; Stabach, Paul; Kavanagh, Dillon; Mullen, Isabelle; Braddock, Alexander A.; Covo, Mariel S.; Tehan, Martin; Yang, Guangxiao; Madri, Joseph A.; Braddock, Demetrios T.] Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06510 USA.
[Cao, Wenxiang; De La Cruz, Enrique M.] Yale Univ, Dept Mol Biophys & Biochem, New Haven, CT 06520 USA.
[Cheng, Zhiliang; Bouchard, Keith; Yu, Zhao-Xue] Alexion, Cheshire, CT 06410 USA.
[Thorn, Stephanie; Wang, Xiangning; Sinusas, Albert J.] Yale Univ, Dept Med & Diagnost Radiol, Sch Med, New Haven, CT 06510 USA.
[Folta-Stogniew, Ewa J.] Yale Univ, WM Keck Biotechnol Res Lab, Sch Med, New Haven, CT 06511 USA.
[Negrete, Alejandro; Shiloach, Joseph] NIDDK, Biotechnol Core Lab, NIH, Rockville, MD 20852 USA.
[Zubal, George] Z Concepts LLC, East Haven, CT 06512 USA.
RP Braddock, DT (reprint author), Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06510 USA.
EM demetrios.braddock@yale.edu
FU Alexion Pharmaceuticals Inc.; Connecticut Bioscience Innovation Fund;
Yale University Department of Pathology; State of Connecticut under the
Connecticut Bioscience Innovations Fund
FX These studies were financially supported by research grants from Alexion
Pharmaceuticals Inc., The Connecticut Bioscience Innovation Fund, and
Yale University Department of Pathology. DTB acknowledges helpful
conversations with Michael Hodsdon (Eli Lily), Elias Lolis (Yale), and
John Louis (NIH/NIDDK/Laboratory of Chemical Physics), and Dr Jon Morrow
(Yale) for his enthusiastic support and encouragement throughout the
course of this study. This material is based on work supported in part
by the State of Connecticut under the Connecticut Bioscience Innovations
Fund. Its contents are solely the responsibility of the authors and do
not necessarily represent the official views of the State of Connecticut
or Connecticut Innovations, Incorporated.
NR 39
TC 7
Z9 8
U1 2
U2 5
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 DEC
PY 2015
VL 6
AR 10006
DI 10.1038/ncomms10006
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DA1PG
UT WOS:000367567100001
PM 26624227
ER
PT J
AU Alioto, TS
Buchhalter, I
Derdak, S
Hutter, B
Eldridge, MD
Hovig, E
Heisler, LE
Beck, TA
Simpson, JT
Tonon, L
Sertier, AS
Patch, AM
Jager, N
Ginsbach, P
Drews, R
Paramasivam, N
Kabbe, R
Chotewutmontri, S
Diessl, N
Previti, C
Schmidt, S
Brors, B
Feuerbach, L
Heinold, M
Grobner, S
Korshunov, A
Tarpey, PS
Butler, AP
Hinton, J
Jones, D
Menzies, A
Raine, K
Shepherd, R
Stebbings, L
Teague, JW
Ribeca, P
Giner, FC
Beltran, S
Raineri, E
Dabad, M
Heath, SC
Gut, M
Denroche, RE
Harding, NJ
Yamaguchi, TN
Fujimoto, A
Nakagawa, H
Quesada, C
Valdes-Mas, R
Nakken, S
Vodak, D
Bower, L
Lynch, AG
Anderson, CL
Waddell, N
Pearson, JV
Grimmond, SM
Peto, M
Spellman, P
He, MH
Kandoth, C
Lee, S
Zhang, J
Letourneau, L
Ma, S
Seth, S
Torrents, D
Xi, L
Wheeler, DA
Lopez-Otin, C
Campo, E
Campbell, PJ
Boutros, PC
Puente, XS
Gerhard, DS
Pfister, SM
McPherson, JD
Hudson, TJ
Schlesner, M
Lichter, P
Eils, R
Jones, DTW
Gut, IG
AF Alioto, Tyler S.
Buchhalter, Ivo
Derdak, Sophia
Hutter, Barbara
Eldridge, Matthew D.
Hovig, Eivind
Heisler, Lawrence E.
Beck, Timothy A.
Simpson, Jared T.
Tonon, Laurie
Sertier, Anne-Sophie
Patch, Ann-Marie
Jaeger, Natalie
Ginsbach, Philip
Drews, Ruben
Paramasivam, Nagarajan
Kabbe, Rolf
Chotewutmontri, Sasithorn
Diessl, Nicolle
Previti, Christopher
Schmidt, Sabine
Brors, Benedikt
Feuerbach, Lars
Heinold, Michael
Groebner, Susanne
Korshunov, Andrey
Tarpey, Patrick S.
Butler, Adam P.
Hinton, Jonathan
Jones, David
Menzies, Andrew
Raine, Keiran
Shepherd, Rebecca
Stebbings, Lucy
Teague, Jon W.
Ribeca, Paolo
Giner, Francesc Castro
Beltran, Sergi
Raineri, Emanuele
Dabad, Marc
Heath, Simon C.
Gut, Marta
Denroche, Robert E.
Harding, Nicholas J.
Yamaguchi, Takafumi N.
Fujimoto, Akihiro
Nakagawa, Hidewaki
Quesada, Ctor
Valdes-Mas, Rafael
Nakken, Sigve
Vodak, Daniel
Bower, Lawrence
Lynch, Andrew G.
Anderson, Charlotte L.
Waddell, Nicola
Pearson, John V.
Grimmond, Sean M.
Peto, Myron
Spellman, Paul
He, Minghui
Kandoth, Cyriac
Lee, Semin
Zhang, John
Letourneau, Louis
Ma, Singer
Seth, Sahil
Torrents, David
Xi, Liu
Wheeler, David A.
Lopez-Otin, Carlos
Campo, Elias
Campbell, Peter J.
Boutros, Paul C.
Puente, Xose S.
Gerhard, Daniela S.
Pfister, Stefan M.
McPherson, John D.
Hudson, Thomas J.
Schlesner, Matthias
Lichter, Peter
Eils, Roland
Jones, David T. W.
Gut, Ivo G.
TI A comprehensive assessment of somatic mutation detection in cancer using
whole-genome sequencing
SO NATURE COMMUNICATIONS
LA English
DT Article
ID ACUTE MYELOID-LEUKEMIA; VARIANT ANALYSIS; POINT MUTATIONS; EXOME;
ACCURATE; MEDULLOBLASTOMA; SIGNATURES; FRAMEWORK; CONSENSUS; ALIGNMENT
AB As whole-genome sequencing for cancer genome analysis becomes a clinical tool, a full understanding of the variables affecting sequencing analysis output is required. Here using tumour-normal sample pairs from two different types of cancer, chronic lymphocytic leukaemia and medulloblastoma, we conduct a benchmarking exercise within the context of the International Cancer Genome Consortium. We compare sequencing methods, analysis pipelines and validation methods. We show that using PCR-free methods and increasing sequencing depth to similar to 100 x shows benefits, as long as the tumour: control coverage ratio remains balanced. We observe widely varying mutation call rates and low concordance among analysis pipelines, reflecting the artefact-prone nature of the raw data and lack of standards for dealing with the artefacts. However, we show that, using the benchmark mutation set we have created, many issues are in fact easy to remedy and have an immediate positive impact on mutation detection accuracy.
C1 [Alioto, Tyler S.; Derdak, Sophia; Ribeca, Paolo; Giner, Francesc Castro; Beltran, Sergi; Raineri, Emanuele; Dabad, Marc; Heath, Simon C.; Gut, Marta; Gut, Ivo G.] BIST, Ctr Genom Regulat, CNAG CRG, Barcelona 08028, Spain.
[Alioto, Tyler S.; Derdak, Sophia; Ribeca, Paolo; Giner, Francesc Castro; Beltran, Sergi; Raineri, Emanuele; Dabad, Marc; Heath, Simon C.; Gut, Marta; Gut, Ivo G.] Univ Pompeu Fabra, Barcelona 08002, Spain.
[Buchhalter, Ivo; Jaeger, Natalie; Ginsbach, Philip; Drews, Ruben; Paramasivam, Nagarajan; Kabbe, Rolf; Schlesner, Matthias; Eils, Roland] German Canc Res Ctr, Div Theoret Bioinformat, D-69120 Heidelberg, Germany.
[Buchhalter, Ivo; Hutter, Barbara; Schmidt, Sabine; Brors, Benedikt; Feuerbach, Lars] German Canc Res Ctr, Div Appl Bioinformat, D-69120 Heidelberg, Germany.
[Eldridge, Matthew D.; Bower, Lawrence; Lynch, Andrew G.; Anderson, Charlotte L.] Univ Cambridge, Li Ka Shing Ctr, Canc Res, UK Cambridge Inst, Cambridge CB2 0RE, England.
[Hovig, Eivind; Nakken, Sigve; Vodak, Daniel] Oslo Univ Hosp, Inst Canc Res, Dept Tumor Biol, N-0424 Oslo, Norway.
[Hovig, Eivind] Univ Oslo, Dept Informat, N-0373 Oslo, Norway.
[Heisler, Lawrence E.; Beck, Timothy A.; Simpson, Jared T.; Denroche, Robert E.; Harding, Nicholas J.; Yamaguchi, Takafumi N.; McPherson, John D.; Hudson, Thomas J.] Ontario Inst Canc Res, Toronto, ON M5G 0A3, Canada.
[Tonon, Laurie; Sertier, Anne-Sophie; Boutros, Paul C.] Ctr Leon Berard, Synergie Lyon Canc Fdn, F-69373 Lyon, France.
[Patch, Ann-Marie; Waddell, Nicola; Pearson, John V.; Grimmond, Sean M.] Univ Queensland, Inst Mol Biosci, Queensland Ctr Med Gen, Brisbane, Qld 4072, Australia.
[Patch, Ann-Marie; Waddell, Nicola; Pearson, John V.] QIMR Berghofer Med Res Inst, Brisbane, Qld 4006, Australia.
[Jaeger, Natalie] Stanford Univ, Dept Genet, Stanford, CA 94305 USA.
[Chotewutmontri, Sasithorn; Diessl, Nicolle; Previti, Christopher] German Canc Res Ctr, Genome & Proteome Core Facil, D-69120 Heidelberg, Germany.
[Heinold, Michael; Pfister, Stefan M.] Univ Heidelberg Hosp, Dept Pediat Hematol & Oncol, D-69120 Heidelberg, Germany.
[Groebner, Susanne] Univ Heidelberg Hosp, Dept Neuropathol, D-69120 Heidelberg, Germany.
[Korshunov, Andrey; Tarpey, Patrick S.; Butler, Adam P.; Hinton, Jonathan; Jones, David; Menzies, Andrew; Raine, Keiran; Shepherd, Rebecca; Stebbings, Lucy; Teague, Jon W.; Campbell, Peter J.] Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England.
[Fujimoto, Akihiro; Nakagawa, Hidewaki] RIKEN, Ctr Integrat Med Sci, Minato Ku, Tokyo 1088639, Japan.
[Quesada, Ctor; Valdes-Mas, Rafael; Lopez-Otin, Carlos; Puente, Xose S.] Univ Oviedo IUOPA, Oviedo 33006, Spain.
[Vodak, Daniel] Oslo Univ Hosp, Inst Canc Genet & Informat, Bioinformat Core Facil, N-0310 Oslo, Norway.
[Anderson, Charlotte L.] Univ Melbourne, Victorian Life Sci Computat Initiat, Melbourne, Vic 3053, Australia.
[Grimmond, Sean M.] Univ Glasgow, Inst Canc Sci, WolfsonWohl Canc Res Ctr, Glasgow G61 1QH, Lanark, Scotland.
[Peto, Myron; Spellman, Paul] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97239 USA.
[He, Minghui] BGI Shenzhen, Shenzhen 518083, Peoples R China.
[Kandoth, Cyriac] Washington Univ, Genome Inst, St Louis, MO 63108 USA.
[Lee, Semin; Zhang, John] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Zhang, John; Seth, Sahil] MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Letourneau, Louis] McGill Univ, Montreal, PQ H3A 0G4, Canada.
[Ma, Singer] Univ Calif Santa Cruz, Ctr Biomol Sci & Engn, Santa Cruz, CA 95064 USA.
[Torrents, David] Barcelona Supercomputing Ctr, IRB BSC Joint Res Program Computat Biol, Barcelona 08034, Spain.
[Xi, Liu; Wheeler, David A.] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA.
[Campo, Elias] Univ Barcelona, Hosp Clin, Dept Pathol, Inst Invest Biomed August Pi & Sunyer,Hematopatho, Barcelona 08036, Spain.
[Boutros, Paul C.; McPherson, John D.; Hudson, Thomas J.] Univ Toronto, Dept Med Biophys, Toronto, ON M5G 1L7, Canada.
[Gerhard, Daniela S.] NCI, Off Canc Gen, Bethesda, MD 20892 USA.
[Pfister, Stefan M.] German Canc Res Ctr, Div Pediat Neurooncol, D-69120 Heidelberg, Germany.
[Hudson, Thomas J.] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 1A8, Canada.
[Lichter, Peter] German Canc Res Ctr, Div Mol Genet, D-69120 Heidelberg, Germany.
[Lichter, Peter; Eils, Roland] German Canc Res Ctr, Heidelberg Ctr Personalised Oncol DKFZ HIPO, Heidelberg, Germany.
[Eils, Roland] Heidelberg Univ, Inst Pharm & Mol Biotechnol, D-69120 Heidelberg, Germany.
[Eils, Roland] Heidelberg Univ, Bioquant Ctr, D-69120 Heidelberg, Germany.
[Jones, David T. W.] German Canc Res Ctr, Div Pediat Neurooncol, D-69120 Heidelberg, Germany.
RP Gut, IG (reprint author), DNAnexus, 1975W El Camino Real,Suite 101, Mountain View, CA 94040 USA.
EM ivo.gut@cnag.crg.eu
RI Eils, Roland/B-6121-2009; Alioto, Tyler/K-7267-2015; Torrents,
David/G-5785-2015; Dabad, Marc/M-9522-2015; Lee, Semin/S-2629-2016;
McPherson, John/D-2633-2017; Quesada, Victor/B-6557-2014; Hovig,
Eivind/H-2474-2011; Pfister, Stefan/F-6860-2013; Beltran,
Sergi/I-3408-2015; Waddell, Nic/H-4929-2015; Grimmond, Sean/J-5304-2016;
Lopez-Otin, Carlos/C-6657-2013; Brors, Benedikt/E-5620-2013; Pearson,
John/F-2249-2011; Campo, elias/O-7192-2016;
OI Eils, Roland/0000-0002-0034-4036; Alioto, Tyler/0000-0002-2960-5420;
Castro-Giner, Francesc/0000-0001-6111-0754; Torrents,
David/0000-0002-6086-9037; Vodak, Daniel/0000-0003-0015-6577;
Suarez-Puente, Xose/0000-0001-9525-1483; Hutter,
Barbara/0000-0002-9034-0329; Buchhalter, Ivo/0000-0003-0764-5832;
Yamaguchi, Takafumi/0000-0003-1082-3871; Dabad,
Marc/0000-0002-6094-747X; Lee, Semin/0000-0002-9015-6046; McPherson,
John/0000-0001-8049-9347; Quesada, Victor/0000-0002-8398-3457; Hovig,
Eivind/0000-0002-9103-1077; Pfister, Stefan/0000-0002-5447-5322;
Beltran, Sergi/0000-0002-2810-3445; Grimmond, Sean/0000-0002-8102-7998;
Lopez-Otin, Carlos/0000-0001-6964-1904; Brors,
Benedikt/0000-0001-5940-3101; Pearson, John/0000-0003-0904-4598; Campo,
elias/0000-0001-9850-9793; Drews, Ruben/0000-0001-7360-4970; Nakken,
Sigve/0000-0001-8468-2050
FU European Commission Framework Programme 7 [FP7 Health-F42008-201418,
262055, 261123]; ICGC-CLL through the Spanish Ministry of Science and
Innovation (MICINN); Instituto de Salud Carlos III (ISCIII); Generalitat
de Catalunya; PedBrain Tumor Project - German Cancer Aid [109252];
German Federal Ministry of Education and Research (BMBF) [01KU1201A,
0315416C, 01GS0883]; BMBF [01KU1001A, 01KU1002B, 031A537A, 031A537C];
Ontario Institute for Cancer Research; Government of Ontario, Ministry
of Research and Innovation; Canada Foundation for Innovation; Movember
Foundation; Terry Fox Research Institute New Investigator Award; CIHR
New Investigator Award; Genome Canada Large-Scale Applied Project
Contract; French National Institute of Cancer (INCa); ABS4NGS ANR
[ANR-11-BINF-0001-06]; RIKEN President's Fund; Cancer Research UK, the
University of Cambridge; Torres Quevedo subprogramme (MICINN)
[PTQ-12-05391]; Research Council of Norway [221580, 218241]; Norwegian
Cancer Society [71220-PR-20060433]; Genome Canada; Prostate Cancer
Canada; Hutchison-Whampoa Limited
FX We thank the DKFZ Genomics and Proteomics Core Facility and the OICR
Genome Technologies Platform for provision of sequencing services.
Financial support was provided by the consortium projects READNA under
grant agreement FP7 Health-F42008-201418, ESGI under grant agreement
262055, GEUVADIS under grant agreement 261123 of the European Commission
Framework Programme 7, ICGC-CLL through the Spanish Ministry of Science
and Innovation (MICINN), the Instituto de Salud Carlos III (ISCIII) and
the Generalitat de Catalunya. Additional financial support was provided
by the PedBrain Tumor Project contributing to the ICGC, funded by German
Cancer Aid (109252) and by the German Federal Ministry of Education and
Research (BMBF, grants #01KU1201A, MedSys #0315416C and NGFNplus
#01GS0883), the BMBF-funded ICGC projects on early-onset prostate cancer
and malignant lymphoma (#01KU1001A, #01KU1002B) and via the BMBF-funded
de. NBI HD-HuB network (#031A537A, #031A537C); the Ontario Institute for
Cancer Research to PCB and JDM through funding provided by the
Government of Ontario, Ministry of Research and Innovation; Genome
Canada; the Canada Foundation for Innovation and Prostate Cancer Canada
with funding from the Movember Foundation (PCB). P.C.B. was also
supported by a Terry Fox Research Institute New Investigator Award, a
CIHR New Investigator Award and a Genome Canada Large-Scale Applied
Project Contract. The Synergie Lyon Cancer platform has received support
from the French National Institute of Cancer (INCa) and from the ABS4NGS
ANR project (ANR-11-BINF-0001-06). The ICGC RIKEN study was supported
partially by RIKEN President's Fund 2011, and the supercomputing
resource for the RIKEN study was provided by the Human Genome Center,
University of Tokyo. M.D.E., L.B., A.G.L. and C.L.A. were supported by
Cancer Research UK, the University of Cambridge and Hutchison-Whampoa
Limited. S.D. is supported by the Torres Quevedo subprogramme (MICINN)
under grant agreement PTQ-12-05391. E.H. is supported by the Research
Council of Norway under grant agreements 221580 and 218241 and by the
Norwegian Cancer Society under grant agreement 71220-PR-20060433. We
specially thank Jennifer Jennings for administrating the activity of the
ICGC Verification Working Group and Anna Borrell for administrative
support.
NR 40
TC 19
Z9 19
U1 2
U2 25
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 DEC
PY 2015
VL 6
AR 10001
DI 10.1038/ncomms10001
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DA1TU
UT WOS:000367579200001
PM 26647970
ER
PT J
AU Dal Monte, O
Costa, VD
Noble, PL
Murray, EA
Averbeck, BB
AF Dal Monte, Olga
Costa, Vincent D.
Noble, Pamela L.
Murray, Elisabeth A.
Averbeck, Bruno B.
TI Amygdala lesions in rhesus macaques decrease attention to threat
SO NATURE COMMUNICATIONS
LA English
DT Article
ID FACIAL EXPRESSIONS; MONKEY AMYGDALA; NEURAL RESPONSES; CINGULATE CORTEX;
EYE CONTACT; EMOTION; DAMAGE; FACES; FEAR; RECOGNITION
AB Evidence from animal and human studies has suggested that the amygdala plays a role in detecting threat and in directing attention to the eyes. Nevertheless, there has been no systematic investigation of whether the amygdala specifically facilitates attention to the eyes or whether other features can also drive attention via amygdala processing. The goal of the present study was to examine the effects of amygdala lesions in rhesus monkeys on attentional capture by specific facial features, as well as gaze patterns and changes in pupil dilation during free viewing. Here we show reduced attentional capture by threat stimuli, specifically the mouth, and reduced exploration of the eyes in free viewing in monkeys with amygdala lesions. Our findings support a role for the amygdala in detecting threat signals and in directing attention to the eye region of faces when freely viewing different expressions.
C1 [Dal Monte, Olga; Costa, Vincent D.; Noble, Pamela L.; Murray, Elisabeth A.; Averbeck, Bruno B.] NIMH, Neuropsychol Lab, NIH, Bethesda, MD 20892 USA.
RP Averbeck, BB (reprint author), NIMH, Neuropsychol Lab, NIH, Bethesda, MD 20892 USA.
EM averbeckbb@mail.nih.gov
OI Murray, Elisabeth/0000-0003-1450-1642; Costa,
Vincent/0000-0002-5412-8945
FU National Institute of Mental Health Intramural Research Programme
FX We are grateful to the staff of the Veterinary Medicine and Resources
Branch at National Institute of Mental Health, NIH, for offering their
facilities and support during data collection. We thank Andrew Mitz,
David Ide, and George Dold for their technical support, and Daniel Reed
Lucas III for his help with animal training. This study was supported by
the National Institute of Mental Health Intramural Research Programme
(O.D.M., V.D.C., P.L.N., E.A.M. and B.B.A).
NR 49
TC 3
Z9 3
U1 3
U2 5
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 DEC
PY 2015
VL 6
AR 10161
DI 10.1038/ncomms10161
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DA1RQ
UT WOS:000367573600001
PM 26658670
ER
PT J
AU Perlman, EJ
Gadd, S
Arold, ST
Radhakrishnan, A
Gerhard, DS
Jennings, L
Huff, V
Auvil, JMG
Davidsen, TM
Dome, JS
Meerzaman, D
Hsu, CH
Nguyen, C
Anderson, J
Ma, Y
Mungall, AJ
Moore, RA
Marra, MA
Mullighan, CG
Ma, J
Wheeler, DA
Hampton, OA
Gastier-Foster, JM
Ross, N
Smith, MA
AF Perlman, Elizabeth J.
Gadd, Samantha
Arold, Stefan T.
Radhakrishnan, Anand
Gerhard, Daniela S.
Jennings, Lawrence
Huff, Vicki
Auvil, Jaime M. Guidry
Davidsen, Tanja M.
Dome, Jeffrey S.
Meerzaman, Daoud
Hsu, Chih Hao
Cu Nguyen
Anderson, James
Ma, Yussanne
Mungall, Andrew J.
Moore, Richard A.
Marra, Marco A.
Mullighan, Charles G.
Ma, Jing
Wheeler, David A.
Hampton, Oliver A.
Gastier-Foster, Julie M.
Ross, Nicole
Smith, Malcolm A.
TI MLLT1 YEATS domain mutations in clinically distinctive Favourable
Histology Wilms tumours
SO NATURE COMMUNICATIONS
LA English
DT Article
ID RNA-POLYMERASE-II; ELONGATION COMPLEX SEC; CHILDRENS ONCOLOGY GROUP;
MIXED-LINEAGE LEUKEMIA; TRANSCRIPTIONAL ELONGATION; CHROMATIN
MODIFICATION; H3K79 METHYLATION; GENETIC-VARIATION; CANCER; PROTEIN
AB Wilms tumour is an embryonal tumour of childhood that closely resembles the developing kidney. Genomic changes responsible for the development of the majority of Wilms tumours remain largely unknown. Here we identify recurrent mutations within Wilms tumours that involve the highly conserved YEATS domain of MLLT1 (ENL), a gene known to be involved in transcriptional elongation during early development. The mutant MLLT1 protein shows altered binding to acetylated histone tails. Moreover, MLLT1-mutant tumours show an increase in MYC gene expression and HOX dysregulation. Patients with MLLT1-mutant tumours present at a younger age and have a high prevalence of precursor intralobar nephrogenic rests. These data support a model whereby activating MLLT1 mutations early in renal development result in the development of Wilms tumour.
C1 [Perlman, Elizabeth J.; Gadd, Samantha; Jennings, Lawrence] Northwestern Univ, Ann & Robert H Lurie Childrens Hosp Chicago, Feinberg Sch Med, Dept Pathol, Chicago, IL 60611 USA.
[Arold, Stefan T.; Radhakrishnan, Anand] King Abdullah Univ Sci & Technol, Dept Biochem & Mol Biol, Div Biol & Environm Sci & Engn, Computat Biosci Res Ctr, Thuwal 23955, Saudi Arabia.
[Gerhard, Daniela S.; Auvil, Jaime M. Guidry; Davidsen, Tanja M.] NCI, Off Canc Gen, Bethesda, MD 20892 USA.
[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, Dept Pediat, Washington, DC 20010 USA.
[Meerzaman, Daoud; Hsu, Chih Hao; Cu Nguyen] NCI, NIH, Ctr Biomed Informat & Informat Technol, Bethesda, MD 20892 USA.
[Anderson, James] Frontier Sci & Technol Res Fdn Inc, Madison, WI 53719 USA.
[Ma, Yussanne; Mungall, Andrew J.; Moore, Richard A.; Marra, Marco A.] British Columbia Canc Agcy, Canadas Michael Smith Genome Sci Ctr, Vancouver, BC V5Z 4S6, Canada.
[Mullighan, Charles G.; Ma, Jing] St Jude Childrens Res Hosp, Dept Pathol, Memphis, TN 38105 USA.
[Wheeler, David A.; Hampton, Oliver A.] Ohio State Univ, Nationwide Childrens Hosp, Dept Pathol & Lab Med, Columbus, OH 43205 USA.
[Gastier-Foster, Julie M.; Ross, Nicole] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA.
[Gastier-Foster, Julie M.] Ohio State Univ, Coll Med, Dept Pathol, Columbus, OH 43205 USA.
[Gastier-Foster, Julie M.] Ohio State Univ, Coll Med, Dept Pediat, Columbus, OH 43205 USA.
[Smith, Malcolm A.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
RP Perlman, EJ (reprint author), Northwestern Univ, Ann & Robert H Lurie Childrens Hosp Chicago, Feinberg Sch Med, Dept Pathol, 225 E Chicago Ave, Chicago, IL 60611 USA.
EM Eperlman@luriechildrens.org
RI Marra, Marco/B-5987-2008
FU NCI [U10 CA98543]; National Cancer Institute, US National Institutes of
Health [HHSN261200800001E]; Data Coordinating Center; NIH [U10CA42326,
U10CA98543, U24 CA114766, UO1CA88131]; IDP Foundation; American and
Lebanese Syrian Associated Charities of St Jude; King Abdullah
University of Science and Technology
FX The TARGET initiative is supported by NCI Grant U10 CA98543. Work
performed under contracts from the National Cancer Institute, US
National Institutes of Health within HHSN261200800001E include specimen
processing (the Children's Oncology Group Biopathology Center (BPC),
whole genomic sequencing (Complete Genomics, Inc), whole exomic
sequencing (Baylor College of Medicine) and specific capture followed by
sequencing (British Columbia Cancer Agency Genome Sciences Centre). The
content of this publication does not necessarily reflect the views of
policies of the Department of Health and Human Services, nor does
mention of trade names, commercial products, or organizations imply
endorsement by the US Government. The authors thank Patee Gesuwan and
Leandro Hermida and the Data Coordinating Center for their support. We
thank Karen Carty and Franceline Huser and for help and assistance with
the recombinant protein production and DSF analysis. We thank the KAUST
bioscience core lab for access to the MicroCal ITC200 microcalorimeter.
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.
The authors are grateful for the project management expertize of Karen
Novik and Laura Monovich, and for the technical expertize of 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 disciplines both at the local institutions and
centrally within the Children's Oncology Group. They enable the
coordination and accurate annotation required for the therapeutic and
biology protocols that form the basis for the TARGET studies. Financial
Support: NCI U10 CA98543 (E.J.P., J.M.G.-F. and M.A.M.); NIH U10CA42326
(E.J.P.); U10CA98543 (J.S.D. and E.J.P.); U24 CA114766; UO1CA88131
(E.J.P.), the IDP Foundation (E.J.P.), the American and Lebanese Syrian
Associated Charities of St Jude (J.M. and C.M.) and the King Abdullah
University of Science and Technology (S.T.A. and A.R.).
NR 64
TC 3
Z9 3
U1 0
U2 4
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-1723
J9 NAT COMMUN
JI Nat. Commun.
PD DEC
PY 2015
VL 6
AR 10013
DI 10.1038/ncomms10013
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DA1PJ
UT WOS:000367567400001
PM 26635203
ER
PT J
AU Poldrack, RA
Laumann, TO
Koyejo, O
Gregory, B
Hover, A
Chen, MY
Gorgolewski, KJ
Luci, J
Joo, SJ
Boyd, RL
Hunicke-Smith, S
Simpson, ZB
Caven, T
Sochat, V
Shine, JM
Gordon, E
Snyder, AZ
Adeyemo, B
Petersen, SE
Glahn, DC
Mckay, DR
Curran, JE
Goring, HHH
Carless, MA
Blangero, J
Dougherty, R
Leemans, A
Handwerker, DA
Frick, L
Marcotte, EM
Mumford, JA
AF Poldrack, Russell A.
Laumann, Timothy O.
Koyejo, Oluwasanmi
Gregory, Brenda
Hover, Ashleigh
Chen, Mei-Yen
Gorgolewski, Krzysztof J.
Luci, Jeffrey
Joo, Sung Jun
Boyd, Ryan L.
Hunicke-Smith, Scott
Simpson, Zack Booth
Caven, Thomas
Sochat, Vanessa
Shine, James M.
Gordon, Evan
Snyder, Abraham Z.
Adeyemo, Babatunde
Petersen, Steven E.
Glahn, David C.
Mckay, D. Reese
Curran, Joanne E.
Goering, Harald H. H.
Carless, Melanie A.
Blangero, John
Dougherty, Robert
Leemans, Alexander
Handwerker, Daniel A.
Frick, Laurie
Marcotte, Edward M.
Mumford, Jeanette A.
TI Long-term neural and physiological phenotyping of a single human
SO NATURE COMMUNICATIONS
LA English
DT Article
ID HUMAN CONNECTOME PROJECT; SURFACE-BASED ANALYSIS; HUMAN BRAIN; NETWORK
ANALYSIS; CEREBRAL-CORTEX; MOOD DISORDERS; TIME-SERIES; FMRI; SYSTEM;
MRI
AB Psychiatric disorders are characterized by major fluctuations in psychological function over the course of weeks and months, but the dynamic characteristics of brain function over this timescale in healthy individuals are unknown. Here, as a proof of concept to address this question, we present the MyConnectome project. An intensive phenome-wide assessment of a single human was performed over a period of 18 months, including functional and structural brain connectivity using magnetic resonance imaging, psychological function and physical health, gene expression and metabolomics. A reproducible analysis workflow is provided, along with open access to the data and an online browser for results. We demonstrate dynamic changes in brain connectivity over the timescales of days to months, and relations between brain connectivity, gene expression and metabolites. This resource can serve as a testbed to study the joint dynamics of human brain and metabolic function over time, an approach that is critical for the development of precision medicine strategies for brain disorders.
C1 [Poldrack, Russell A.; Chen, Mei-Yen; Joo, Sung Jun; Boyd, Ryan L.; Mumford, Jeanette A.] Univ Texas Austin, Dept Psychol, Austin, TX 78712 USA.
[Poldrack, Russell A.; Luci, Jeffrey] Univ Texas Austin, Dept Neurosci, Austin, TX 78712 USA.
[Poldrack, Russell A.; Gregory, Brenda; Hover, Ashleigh; Luci, Jeffrey; Frick, Laurie] Univ Texas Austin, Imaging Res Ctr, Austin, TX 78712 USA.
[Poldrack, Russell A.; Koyejo, Oluwasanmi; Gorgolewski, Krzysztof J.; Shine, James M.] Stanford Univ, Dept Psychol, Stanford, CA 94305 USA.
[Laumann, Timothy O.; Gordon, Evan; Snyder, Abraham Z.; Adeyemo, Babatunde; Petersen, Steven E.] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA.
[Hunicke-Smith, Scott] Univ Texas Austin, Genome Sequencing & Anal Facil, Austin, TX 78712 USA.
[Simpson, Zack Booth; Marcotte, Edward M.] Univ Texas Austin, Ctr Syst & Synthet Biol, Austin, TX 78712 USA.
[Caven, Thomas] Univ Med Ctr Brackenridge, Austin, TX 78701 USA.
[Sochat, Vanessa] Stanford Univ, Biomed Informat Program, Stanford, CA 94305 USA.
[Glahn, David C.; Mckay, D. Reese] Inst Living, Olin Neuropsychiat Res Ctr, Hartford, CT 06114 USA.
[Glahn, David C.; Mckay, D. Reese] Yale Univ, Sch Med, Dept Psychiat, New Haven, CT 06511 USA.
[Curran, Joanne E.; Blangero, John] Univ Texas Rio Grande Valley, South Texas Diabet & Obes Inst, Sch Med, Brownsville, TX 78520 USA.
[Goering, Harald H. H.; Carless, Melanie A.] Texas Biomed Res Inst, San Antonio, TX 78227 USA.
[Dougherty, Robert] Stanford Univ, Ctr Neurobiol Imaging, Stanford, CA 94305 USA.
[Leemans, Alexander] Univ Med Ctr Utrecht, Image Sci Inst, NL-3584 CX Utrecht, Netherlands.
[Handwerker, Daniel A.] NIMH, Bethesda, MD 20892 USA.
[Marcotte, Edward M.] Univ Texas Austin, Dept Mol Biosci, Austin, TX 78712 USA.
RP Poldrack, RA (reprint author), Univ Texas Austin, Dept Psychol, Austin, TX 78712 USA.
EM poldrack@stanford.edu
RI Leemans, Alexander/A-1784-2011;
OI Gorgolewski, Krzysztof/0000-0003-3321-7583; Leemans,
Alexander/0000-0002-9306-6126; Gordon, Evan/0000-0002-2276-5237;
Poldrack, Russell/0000-0001-6755-0259
FU Texas Emerging Technology Fund; James S. McDonnell Foundation
Collaborative Activity award; National Institutes of Health [MH100872,
NS0046424, GM076536, OD009572, MH078143, MH078111, MH083824]; National
Science Foundation [1131441, 1237975]; Netherlands Organisation for
Scientific Research (VIDI Grant) [639.072.411]; Welch Foundation
[F1515]; Australian National Health and Medical Research Council
[GNT1072403]; William R. Hewlett Stanford Graduate Fellowship; Cancer
Prevention Research Institute of Texas; Population Research Center at UT
Austin [5R24HD042849]
FX This research was supported by the Texas Emerging Technology Fund (to
Daniel Johnston, PI), James S. McDonnell Foundation Collaborative
Activity award (to S.E.P.), National Institutes of Health (MH100872 to
T.L., NS0046424 to S.E.P., GM076536 and OD009572 to E.M.M., MH078143 to
D.G., MH078111 to J.B., MH083824 to D.G. and J.B.), National Science
Foundation (1131441 to R.A.P., 1237975 to E.M.M.), Netherlands
Organisation for Scientific Research (VIDI Grant 639.072.411 to A.L.),
Welch Foundation (F1515 to E.M.M.), Australian National Health and
Medical Research Council (GNT1072403 to J.M.S.), William R. Hewlett
Stanford Graduate Fellowship (to V.S.) and the Cancer Prevention
Research Institute of Texas (to E.M.M.). REDCap at UT is supported by
5R24HD042849 awarded to the Population Research Center at UT Austin. The
content is solely the responsibility of the authors and does not
necessarily represent the official views of the National Institutes of
Health. Thanks to Neeta Bakhta for assistance with blood draws and
laboratory analyses, Terry Heckman and Margaret Lutz for processing of
blood samples, Dhivya Arasappan for assistance with bioinformatics, Joan
Balash for assistance with audiometry, and Jacy Anthis, Ashley Armenita,
Adiel Carlo, Andrew Coulter, Jave Del Rosario, Dustin Fry, Kristie
Garza, Kelly Jameson, Seorin Kim, Christina Leuker, Lakshya Nagar, Jacob
Perez, Grace Shearrer and Sheila Zare for assistance with MRI scanning.
Thanks to Kalanit Grill-Spector, Anthony Stigliani and Evelina Federenko
for providing localizer task software. We also thank the following
individuals for helpful discussion and assistance at various points in
the project: Tim Behrens, Robert Bilder, Randy Buckner, Rui Chen, Eliza
Congdon, Maude David, George Georgiou, Matt Glasser, Steve Hanson, Alex
Huk, Saad Jbabdi, Michael Milham, Nolan Nichols, Tom Nichols, James
Pennebaker, Katie Pollard, Rajeev Raizada, Tom Schonberg, Michael
Snyder, Stamatios Sotiropoulos, Emily Tsang, David Van Essen, Gael
Varoquaux and Michael Waskom.
NR 74
TC 14
Z9 14
U1 4
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 DEC
PY 2015
VL 6
AR 8885
DI 10.1038/ncomms9885
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DA1TC
UT WOS:000367577400002
PM 26648521
ER
PT J
AU Tran, DT
Masedunskas, A
Weigert, R
Ten Hagen, KG
AF Tran, Duy T.
Masedunskas, Andrius
Weigert, Roberto
Ten Hagen, Kelly G.
TI Arp2/3-mediated F-actin formation controls regulated exocytosis in vivo
SO NATURE COMMUNICATIONS
LA English
DT Article
ID FUSED SECRETORY VESICLES; ARP2/3 COMPLEX; COMPENSATORY ENDOCYTOSIS;
CHROMAFFIN CELLS; MUC2 MUCIN; MYOSIN-II; INTRAVITAL MICROSCOPY;
SALIVARY-GLAND; DROSOPHILA; PROTEIN
AB The actin cytoskeleton plays crucial roles in many cellular processes, including regulated secretion. However, the mechanisms controlling F-actin dynamics in this process are largely unknown. Through 3D time-lapse imaging in a secreting organ, we show that F-actin is actively disassembled along the apical plasma membrane at the site of secretory vesicle fusion and re-assembled directionally on vesicle membranes. Moreover, we show that fusion pore formation and PIP2 redistribution precedes actin and myosin recruitment to secretory vesicle membranes. Finally, we show essential roles for the branched actin nucleators Arp2/3- and WASp in the process of secretory cargo expulsion and integration of vesicular membranes with the apical plasma membrane. Our results highlight previously unknown roles for branched actin in exocytosis and provide a genetically tractable system to image the temporal and spatial dynamics of polarized secretion in vivo.
C1 [Tran, Duy T.; Ten Hagen, Kelly G.] NIDCR, Dev Glycobiol Sect, NIH, Bethesda, MD 20892 USA.
[Masedunskas, Andrius; Weigert, Roberto] NIDCR, Intracellular Membrane Trafficking Sect, NIH, Bethesda, MD 20892 USA.
[Masedunskas, Andrius] Univ New S Wales, Sch Med Sci, Oncol Res Unit, Sydney, NSW 2052, Australia.
RP Ten Hagen, KG (reprint author), NIDCR, Dev Glycobiol Sect, NIH, Bldg 30,Room 426,30 Convent Dr,MSC 4370, Bethesda, MD 20892 USA.
EM Kelly.Tenhagen@nih.gov
FU Intramural Research Program of the NIDCR, National Institutes of Health
[Z01-DE-000713]
FX We thank our colleagues for many helpful discussions. We thank Jia Guo
for technical assistance. We also thank the Vienna Drosophila RNAi
Center, the Bloomington Stock Center and the Developmental Studies
Hybridoma Bank for fly stocks and other reagents. This work was
supported by the Intramural Research Program of the NIDCR, National
Institutes of Health (Z01-DE-000713 to K.G.T.H.).
NR 51
TC 6
Z9 6
U1 4
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 DEC
PY 2015
VL 6
AR 10098
DI 10.1038/ncomms10098
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DA1QG
UT WOS:000367569800004
PM 26639106
ER
PT J
AU Semba, RD
Lam, M
Sun, K
Zhang, PB
Schaumberg, DA
Ferrucci, L
Ping, PP
Van Eyk, JE
AF Semba, Richard D.
Lam, Maggie
Sun, Kai
Zhang, Pingbo
Schaumberg, Debra A.
Ferrucci, Luigi
Ping, Peipei
Van Eyk, Jennifer E.
TI Priorities and trends in the study of proteins in eye research,
1924-2014
SO PROTEOMICS CLINICAL APPLICATIONS
LA English
DT Article
DE Biological processes; Eye; Human proteome project; Mouse; MS; Proteomics
ID HOMEOBOX-CONTAINING GENE; RETINAL GANGLION-CELLS; COMPLEMENT FACTOR-H;
MACULAR DEGENERATION; MASS-SPECTROMETRY; STRUCTURAL BASIS; VEGF-A;
MUTATIONS; PEDF; MECHANISMS
AB Purpose: To identify the proteins that are relevant to eye research and develop assays for the study of a set of these proteins.
Experimental design: We conducted a bibliometric analysis by merging gene lists for human and mouse from the National Center for Biotechnology Information FTP site and combining them with PubMed references that were retrieved with the search terms "eye" [MeSH Terms] OR "eye" [All Fields] OR "eyes" [All Fields].
Results: For human and mouse eye studies, respectively, the total number of publications was 13 525 and 23 895 and the total number of proteins was 4050 and 4717. For proteins in human andmouse eye studies, respectively, 88.7 and 81.7% had five or fewer citations. The top 50 most intensively studied proteins for human and mouse eye studies were generally in the areas of photoreceptors and phototransduction, inflammation, and angiogenesis, neurodevelopment, lens transparency, and cell-cycle and cellular processes. We proposed selected reaction monitoring assays that were developed in silico for the top fifty most intensively studied proteins in human and mouse eye research.
Conclusions and clinical relevance: We conclude that scientists engaged in eye research tend to focus on the same proteins. Newer resources and tools in proteomics can expand the investigations to lesser-known proteins of the eye.
C1 [Semba, Richard D.; Sun, Kai; Zhang, Pingbo] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21287 USA.
[Lam, Maggie; Ping, Peipei] Univ Calif Los Angeles, David Geffen Sch Med, Dept Physiol, Cardiac Prote & Signaling Lab, Los Angeles, CA 90095 USA.
[Schaumberg, Debra A.] Univ Utah, Sch Med, Moran Eye Ctr, Ctr Translat Med, Salt Lake City, UT USA.
[Schaumberg, Debra A.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Ferrucci, Luigi] NIA, NIH, Baltimore, MD 21224 USA.
[Van Eyk, Jennifer E.] Cedars Sinai Med Ctr, Inst Heart, Adv Clin BioSyst Res Inst, Los Angeles, CA 90048 USA.
[Van Eyk, Jennifer E.] Cedars Sinai Med Ctr, Dept Med, Los Angeles, CA 90048 USA.
RP Semba, RD (reprint author), Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Smith Bldg M015,400 N Broadway, Baltimore, MD 21287 USA.
EM rdsemba@jhmi.edu
FU National Institutes of Health [R01 EY024596, R01 AG027012]; Joint King
Khaled Eye Specialist Hospital; Wilmer Eye Institute Research Grant
Program; Edward N. & Della L. Thome Memorial Foundation; Research to
Prevent Blindness
FX This work was supported by the National Institutes of Health grants R01
EY024596, R01 AG027012, the Joint King Khaled Eye Specialist Hospital
and Wilmer Eye Institute Research Grant Program, the Edward N. & Della
L. Thome Memorial Foundation, and Research to Prevent Blindness.
NR 66
TC 2
Z9 2
U1 0
U2 4
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 DEC
PY 2015
VL 9
IS 11-12
SI SI
BP 1105
EP 1122
DI 10.1002/prca.201500006
PG 18
WC Biochemical Research Methods; Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA DA3UD
UT WOS:000367723600014
PM 26123431
ER
PT J
AU Heindel, JJ
Newbold, RR
Bucher, JR
Camacho, L
Delclos, KB
Lewis, SM
Vanlandingham, M
Churchwell, MI
Twaddle, NC
McLellen, M
Chidambaram, M
Bryant, M
Woodling, K
da Costa, GG
Ferguson, SA
Flaws, J
Howard, PC
Walker, NJ
Zoeller, RT
Fostel, J
Favaro, C
Schug, TT
AF Heindel, Jerrold J.
Newbold, Retha R.
Bucher, John R.
Camacho, Luisa
Delclos, K. Barry
Lewis, Sherry M.
Vanlandingham, Michelle
Churchwell, Mona I.
Twaddle, Nathan C.
McLellen, Michelle
Chidambaram, Mani
Bryant, Matthew
Woodling, Kellie
da Costa, Goncalo Gamboa
Ferguson, Sherry A.
Flaws, Jodi
Howard, Paul C.
Walker, Nigel J.
Zoeller, R. Thomas
Fostel, Jennifer
Favaro, Carolyn
Schug, Thaddeus T.
TI NIEHS/FDA CLARITY-BPA research program update
SO REPRODUCTIVE TOXICOLOGY
LA English
DT Review
DE Bisphenol A; NIEHS; FDA; NTP; CLARITY-BPA; Consortium; Endocrine
disruptors
ID SPRAGUE-DAWLEY RATS; ESTROGEN-RECEPTOR EXPRESSION; BISPHENOL-A; ETHINYL
ESTRADIOL; THYROID-HORMONES; DNA METHYLATION; ORAL-EXPOSURE; CELL
BIOLOGY; FEMALE; TOXICITY
AB Bisphenol A (BPA) is a chemical used in the production of numerous consumer products resulting in potential daily human exposure to this chemical. The FDA previously evaluated the body of BPA toxicology data and determined that BPA is safe at current exposure levels. Although consistent with the assessment of some other regulatory agencies around the world, this determination of BPA safety continues to be debated in scientific and popular publications, resulting in conflicting messages to the public. Thus, the National Toxicology Program (NTP), National Institute of Environmental Health Sciences (NIEHS), and U.S. Food and Drug Administration (FDA) developed a consortium-based research program to link more effectively a variety of hypothesis-based research investigations and guideline-compliant safety testing with BPA. This collaboration is known as the Consortium Linking Academic and Regulatory Insights on BPA Toxicity (CLARITY-BPA). This paper provides a detailed description of the conduct of the study and a midterm update on progress of the CLARITY-BPA research program. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
C1 [Heindel, Jerrold J.; Schug, Thaddeus T.] NIEHS, NIH, Div Extramural Res & Training, Res Triangle Pk, NC 27709 USA.
[Newbold, Retha R.; Bucher, John R.; Walker, Nigel J.; Fostel, Jennifer] NIEHS, NIH, Div Natl Toxicol Program, Res Triangle Pk, NC 27709 USA.
[Camacho, Luisa; Delclos, K. Barry; Vanlandingham, Michelle; Churchwell, Mona I.; Twaddle, Nathan C.; McLellen, Michelle; Chidambaram, Mani; Bryant, Matthew; Woodling, Kellie; da Costa, Goncalo Gamboa] USDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
[Ferguson, Sherry A.] USDA, Div Neurotoxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
[Flaws, Jodi] Univ Illinois, Dept Comparat Biosci, Urbana, IL 61802 USA.
[Lewis, Sherry M.; Howard, Paul C.] USDA, Off Sci Coordinat, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
[Zoeller, R. Thomas] Univ Massachusetts, Dept Biol, Amherst, MA 01003 USA.
[Favaro, Carolyn] NIEHS, Team Vistronix, NTP Comp & User Support, NIH,Div Natl Toxicol Program, Res Triangle Pk, NC 27709 USA.
RP Heindel, JJ (reprint author), NIEHS, NIH, Div Extramural Res & Training, POB 12233, Res Triangle Pk, NC 27709 USA.
EM heindelj@niehs.nih.gov
RI Walker, Nigel/D-6583-2012
OI Walker, Nigel/0000-0002-9111-6855
FU National Toxicology Program; Food and Drug Administration; National
Institute of Environmental Health Sciences/National Institutes of Health
[FDA IAG: 224-12-0003, NIEHS IAG: AES12013]
FX The NCTR portion of the study was conducted under the auspices of the
National Toxicology Program and funded by an Interagency agreement (JAG)
between the Food and Drug Administration and the National Institute of
Environmental Health Sciences/National Institutes of Health (FDA IAG:
224-12-0003; NIEHS IAG: AES12013). We are grateful for the extraordinary
efforts of the NCTR Animal Care, Diet Preparation, Information
Technology, Microbiology, Pathology, Quality Assurance, and Veterinary
Services staffs, the NIP Statistical Support Team of the Division of
Bioinformatics and Biostatistics, as well as Ms. Kathy Carroll of the
Office of Scientific Coordination, in the planning and conduct of this
study. This manuscript was reviewed in accordance with USFDA and NIEHS
procedures prior to submission. The opinions expressed in this paper do
not necessarily reflect those of the USFDA.
NR 34
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U1 8
U2 23
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0890-6238
J9 REPROD TOXICOL
JI Reprod. Toxicol.
PD DEC
PY 2015
VL 58
BP 33
EP 44
DI 10.1016/j.reprotox.2015.07.075
PG 12
WC Reproductive Biology; Toxicology
SC Reproductive Biology; Toxicology
GA DA1MJ
UT WOS:000367559600005
PM 26232693
ER
PT J
AU Song, K
Huang, P
Yi, CL
Ning, B
Hu, S
Nie, LM
Chen, XY
Nie, ZH
AF Song, Kai
Huang, Peng
Yi, Chenglin
Ning, Bo
Hu, Song
Nie, Liming
Chen, Xiaoyuan
Nie, Zhihong
TI Photoacoustic and Colorimetric Visualization of Latent Fingerprints
SO ACS NANO
LA English
DT Article
DE latent fingerprints; colorimetric imaging; photoacoustic imaging; block
copolymer; gold nanoparticles
ID GOLD NANOPARTICLES; ELECTROCHEMILUMINESCENCE; IDENTIFICATION;
FINGERMARKS; METABOLITES; THERAPY
AB There is a high demand on a simple, rapid, accurate, user-friendly, cost-effective, and nondestructive universal method for latent fingerprint (LFP) detection. Herein, we describe a combination imaging strategy for LFP visualization with high resolution using poly(styrene-alt-maleic anhydride)-b-polystyrene (PSMA-b-PS) functionalized gold nanoparticles (GNPs). This general approach integrates the merits of both colorimetric imaging and photoacoustic imaging. In comparison with the previous methods, our strategy is single-step and does not require the signal amplification by silver staining. The PSMA-b-PS functionalized GNPs have good stability, tunable color, and high affinity for universal secretions (proteins/polypeptides/amino acids), which makes our approach general and flexible for visualizing LFPs on different substrates (presumably with different colors) and from different people. Moreover, the unique optical property of GNPs enables the photoacoustic imaging of GNPs-deposited LFPs with high resolution. This allows observation of level 3 hyperfine features of LFPs such as the pores and ridge contours by photoacoustic imaging. This technique can potentially be used to identify chemicals within LFP residues. We believe that this dual-modality-imaging of LFPs will find widespread use in forensic investigations and medical diagnostics.
C1 [Song, Kai] Changchun Normal Univ, Sch Life Sci, Changchun 130032, Peoples R China.
[Huang, Peng] Shenzhen Univ, Guangdong Key Lab Biomed Measurements & Ultrasoun, Dept Biomed Engn, Sch Med, Shenzhen 518060, Peoples R China.
[Song, Kai; Yi, Chenglin; Nie, Zhihong] Univ Maryland, Dept Chem & Biochem, College Pk, MD 20742 USA.
[Ning, Bo; Hu, Song] Univ Virginia, Dept Biomed Engn, Charlottesville, VA 22903 USA.
[Huang, Peng; Nie, Liming; Chen, Xiaoyuan] Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA.
RP Huang, P (reprint author), Shenzhen Univ, Guangdong Key Lab Biomed Measurements & Ultrasoun, Dept Biomed Engn, Sch Med, Shenzhen 518060, Peoples R China.
EM peng.huang@nih.gov; shawn.chen@nih.gov; znie@umd.edu
RI Nie, Zhihong/D-7495-2011; Huang, Peng/R-2480-2016;
OI Nie, Zhihong/0000-0001-9639-905X; Huang, Peng/0000-0003-3651-7813; Ning,
Bo/0000-0002-6006-5696
FU Shenzhen University; University of Maryland; National Natural Science
Foundation of China [81401465, 51573096, 11204021, 81272987]; National
Science Foundation [CHE-1505839]; Intramural Research Program (IRP) of
the NIBIB/NIH
FX This work was supported by the startup funds from the Shenzhen
University and University of Maryland, the National Natural Science
Foundation of China (81401465, 51573096, 11204021, 81272987), the
National Science Foundation (CHE-1505839) and the Intramural Research
Program (IRP) of the NIBIB/NIH.
NR 26
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U1 17
U2 78
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1936-0851
EI 1936-086X
J9 ACS NANO
JI ACS Nano
PD DEC
PY 2015
VL 9
IS 12
BP 12344
EP 12348
DI 10.1021/acsnano.5b05629
PG 5
WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience &
Nanotechnology; Materials Science, Multidisciplinary
SC Chemistry; Science & Technology - Other Topics; Materials Science
GA CZ7LE
UT WOS:000367280100085
PM 26528550
ER
PT J
AU Tian, Q
Resnick, SM
Ferrucci, L
Studenski, SA
AF Tian, Qu
Resnick, Susan M.
Ferrucci, Luigi
Studenski, Stephanie A.
TI Intra-individual lap time variation of the 400-m walk, an early mobility
indicator of executive function decline in high-functioning older
adults?
SO AGE
LA English
DT Article
DE Lap time variation; Executive function; Longitudinal study; Aging
ID MILD COGNITIVE IMPAIRMENT; GAIT SPEED; BODY-COMPOSITION; SLOWER GAIT;
HEALTH ABC; VARIABILITY; ASSOCIATION; PERFORMANCE; DISEASE; POPULATION
AB Higher intra-individual lap time variation (LTV) of the 400-m walk is cross-sectionally associated with poorer attention in older adults. Whether higher LTV predicts decline in executive function and whether the relationship is accounted for by slower walking remain unanswered. The main objective of this study was to examine the relationship between baseline LTV and longitudinal change in executive function. We used data from 347 participants aged 60 years and older (50.7 % female) from the Baltimore Longitudinal Study of Aging. Longitudinal assessments of executive function were conducted between 2007 and 2013, including attention (Trails A, Digit Span Forward Test), cognitive flexibility and set shifting (Trails B, Delta TMT: Trials B minus Trials A), visuoperceptual speed (Digit Symbol Substitution Test), and working memory (Digit Span Backward Test). LTV and mean lap time (MLT) were obtained from the 400-m walk test concurrent with the baseline executive function assessment. LTV was computed as variability of lap time across ten 40-m laps based on individual trajectories. A linear mixed-effects model was used to examine LTV in relation to changes in executive function, adjusted for age, sex, education, and MLT. Higher LTV was associated with greater decline in performance on Trails B (beta=4.322, p<0.001) and delta TMT (beta=4.230, p<0.001), independent of covariates. Findings remained largely unchanged after further adjustment for MLT. LTV was not associated with changes in other executive function measures (all p>0.05). In high-functioning older adults, higher LTV in the 400-m walk predicts executive function decline involving cognitive flexibility and set shifting over a long period of time. High LTV may be an early indicator of executive function decline independent of MLT.
C1 [Tian, Qu; Ferrucci, Luigi; Studenski, Stephanie A.] Natl Inst Aging, Translat Gerontol Branch, Longitudinal Studies Sect, Baltimore, MD 21224 USA.
[Resnick, Susan M.] Natl Inst Aging, Lab Behav Neurosci, Baltimore, MD 21224 USA.
RP Tian, Q (reprint author), 251 Bayview Blvd,Suite 100,Rm 04B316, Baltimore, MD 21224 USA.
EM qu.tian@nih.gov
RI Tian, Qu/E-5266-2015
OI Tian, Qu/0000-0003-2706-1439
FU Intramural Research Program of the National Institute on Aging
FX This research was supported by the Intramural Research Program of the
National Institute on Aging.
NR 47
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U1 3
U2 6
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0161-9152
EI 1574-4647
J9 AGE
JI Age
PD DEC
PY 2015
VL 37
IS 6
AR 115
DI 10.1007/s11357-015-9855-0
PG 9
WC Geriatrics & Gerontology
SC Geriatrics & Gerontology
GA CZ9ET
UT WOS:000367401300011
PM 26561401
ER
PT J
AU Talani, G
Lovinger, DM
AF Talani, Giuseppe
Lovinger, David M.
TI Interactions between ethanol and the endocannabinoid system at GABAergic
synapses on basolateral amygdala principal neurons
SO ALCOHOL
LA English
DT Article
DE Alcohol; CB1 receptor; Synapse; Inhibition; Arachidonoyl ethanolamide;
Cyclic AMP
ID CONDITIONED PLACE PREFERENCE; CANNABINOID CB1 RECEPTORS; NEURON/SYNAPTIC
BOUTON PREPARATION; ACID AMIDE HYDROLASE; ENDOGENOUS CANNABINOIDS;
SEEKING BEHAVIOR; SYNAPTIC-TRANSMISSION; GABA(B) RECEPTORS;
ADENYLATE-CYCLASE; MODULATE ANXIETY
AB The basolateral amygdala (BLA) plays crucial roles in stimulus value coding, as well as drug and alcohol dependence. Ethanol alters synaptic transmission in the BLA, while endocannabinoids (eCBs) produce presynaptic depression at BLA synapses. Recent studies suggest interactions between ethanol and eCBs that have important consequences for alcohol drinking behavior. To determine how ethanol and eCBs interact in the BLA, we examined the physiology and pharmacology of GABAergic synapses onto BLA pyramidal neurons in neurons from young rats. Application of ethanol at concentrations relevant to intoxication increased, in both young and adult animals, the frequency of spontaneous and miniature GABAergic inhibitory postsynaptic currents, indicating a presynaptic site of ethanol action. Ethanol did not potentiate sIPSCs during inhibition of adenylyl cyclase while still exerting its effect during inhibition of protein kinase A. Activation of type 1 cannabinoid receptors (CBI) in the BLA inhibited GABAergic transmission via an apparent presynaptic mechanism, and prevented ethanol potentiation. Surprisingly, ethanol potentiation was also prevented by CBI antagonists/inverse agonists. Brief depolarization of BLA pyramidal neurons suppressed GABAergic transmission (depolarization-induced suppression of inhibition [DSI]), an effect previously shown to be mediated by postsynaptic eCB release and presynaptic CBI activation. A CBI-mediated suppression of GABAergic transmission was also produced by combined afferent stimulation at 0.1 Hz (LFS), and postsynaptic loading with the eCB arachidonoyl ethanolamide (AEA). Both DSI and LFS-induced synaptic depression were prevented by ethanol. Our findings indicate antagonistic interactions between ethanol and eCB/CB1 modulation at GABAergic BLA synapses that may contribute to eCB roles in ethanol seeking and drinking. Published by Elsevier Inc.
C1 [Talani, Giuseppe; Lovinger, David M.] NIAAA, Sect Synapt Pharmacol, Lab Integrat Neurosci, NIH, Bethesda, MD 20892 USA.
[Talani, Giuseppe] CNR, Inst Neurosci, Cagliari, Italy.
RP Lovinger, DM (reprint author), NIAAA, Lab Integrat Neurosci, 5625 Fishers Lane,Room TS-11, Bethesda, MD 20892 USA.
EM lovindav@mail.nih.gov
FU Division of Intramural Clinical and Biological Research of the National
Institute on Alcohol Abuse and Alcoholism [ZIAAA000407]
FX We acknowledge members of the Section on Synaptic Pharmacology,
Laboratory for Integrative Neuroscience for helping us with the research
and preparation of this manuscript, with a special thanks to Dr. Anton
Sheinin for training in the vibrodissociation technique. This work was
supported by the Division of Intramural Clinical and Biological Research
of the National Institute on Alcohol Abuse and Alcoholism ZIAAA000407.
NR 94
TC 1
Z9 1
U1 0
U2 7
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0741-8329
EI 1873-6823
J9 ALCOHOL
JI Alcohol
PD DEC
PY 2015
VL 49
IS 8
BP 781
EP 794
DI 10.1016/j.alcohol.2015.08.006
PG 14
WC Substance Abuse; Pharmacology & Pharmacy; Toxicology
SC Substance Abuse; Pharmacology & Pharmacy; Toxicology
GA CZ9MJ
UT WOS:000367421400004
PM 26603632
ER
PT J
AU Edwards, S
Little, HJ
Richardson, HN
Vendruscolo, LF
AF Edwards, Scott
Little, Hilary J.
Richardson, Heather N.
Vendruscolo, Leandro F.
TI Divergent regulation of distinct glucocorticoid systems in alcohol
dependence
SO ALCOHOL
LA English
DT Article
DE Alcohol-use disorder; Amygdala; Cognition; Corticotropin-releasing
factor; Glucocorticoids; Prefrontal cortex
ID CORTICOTROPIN-RELEASING-FACTOR; PITUITARY-ADRENAL AXIS; STEROID-RECEPTOR
COACTIVATOR-1; POSTTRAUMATIC-STRESS-DISORDER; ANXIETY-LIKE BEHAVIOR;
ETHANOL WITHDRAWAL; ARGININE-VASOPRESSIN; PREFRONTAL CORTEX; CENTRAL
NUCLEUS; V1B RECEPTOR
AB Chronic alcohol consumption disrupts glucocorticoid signaling at multiple physiological levels to interact with several disease-related processes associated with neuroendocrine and psychiatric disorders. Excessive alcohol use produces stress-related neuroadaptations at the level of the hypothalamic-pituitary-adrenal (HPA) axis as well as within central (extra-hypothalamic) neural circuitry, including the central amygdala (CeA) and prefrontal cortex (PFC). Altered glucocorticoid receptor (GR) signaling in these areas following excessive alcohol exposure is postulated to mediate the transition from recreational drinking to dependence, as well as the manifestation of a host of cognitive and neurological deficits. Specifically, a bidirectional regulation of stress systems by glucocorticoids leads to the development of an HPA axis tolerance and a concomitant sensitization of cortical and subcortical circuitries. A greater understanding of how hypothalamic and extra-hypothalamic glucocorticoid systems interact to mediate excessive drinking and related pathologies will lead to more effective therapeutic strategies for alcohol use disorder (AUD) and closely related comorbidities. (C) 2015 Elsevier Inc. All rights reserved.
C1 [Edwards, Scott] Louisiana State Univ, Hlth Sci Ctr, Alcohol & Drug Abuse Ctr Excellence, Dept Physiol, New Orleans, LA 70112 USA.
[Little, Hilary J.] Kings Coll London, Inst Psychiat Psychol & Neurosci, London WC2R 2LS, England.
[Richardson, Heather N.] Univ Massachusetts, Dept Psychol & Brain Sci, Amherst, MA 01003 USA.
[Vendruscolo, Leandro F.] NIDA, NIH, Baltimore, MD USA.
RP Edwards, S (reprint author), Louisiana State Univ, Hlth Sci Ctr, Alcohol & Drug Abuse Ctr Excellence, Dept Physiol, 1901 Perdido St, New Orleans, LA 70112 USA.
EM sedwa5@lsuhsc.edu
FU National Institute on Alcohol Abuse and Alcoholism [AA020839]; National
Institute on Drug Abuse, Intramural Research Program; [AA017581]
FX Preparation of this review was supported by the National Institute on
Alcohol Abuse and Alcoholism (AA020839, SE) and the National Institute
on Drug Abuse, Intramural Research Program (LFV). We thank Dr. Marisa
Roberto and all of the individuals who allowed us to share our work at
the 2014 Alcoholism and Stress Conference in Volterra, Italy (supported
by AA017581).
NR 97
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U1 2
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0741-8329
EI 1873-6823
J9 ALCOHOL
JI Alcohol
PD DEC
PY 2015
VL 49
IS 8
BP 811
EP 816
DI 10.1016/j.alcohol.2015.04.004
PG 6
WC Substance Abuse; Pharmacology & Pharmacy; Toxicology
SC Substance Abuse; Pharmacology & Pharmacy; Toxicology
GA CZ9MJ
UT WOS:000367421400007
PM 26003866
ER
PT J
AU Hiroshima, Y
Maawy, A
Zhang, Y
Guzman, MG
Heim, R
Makings, L
Luiken, GA
Kobayashi, H
Tanaka, K
Endo, I
Hoffman, RM
Bouvet, M
AF Hiroshima, Yukihiko
Maawy, Ali
Zhang, Yong
Guzman, Miguel Garcia
Heim, Roger
Makings, Lew
Luiken, George A.
Kobayashi, Hisataka
Tanaka, Kuniya
Endo, Itaru
Hoffman, Robert M.
Bouvet, Michael
TI Photoimmunotherapy Inhibits Tumor Recurrence After Surgical Resection on
a Pancreatic Cancer Patient-Derived Orthotopic Xenograft (PDOX) Nude
Mouse Model
SO ANNALS OF SURGICAL ONCOLOGY
LA English
DT Article
ID MICE; CARCINOMA; SPECIMENS; TRANSPLANTATION; TISSUE; CEA
AB Background. Photoimmunotherapy (PIT) uses a target-specific photosensitizer based on a near-infrared (NIR) phthalocyanine dye, IR700, to induce tumor necrosis after irradiation with NIR light to kill cancer cells, such as those that remain after surgery. The purpose of the present study was to sterilize the surgical bed after pancreatic cancer resection with PIT in carcinoembryonic antigen (CEA)expressing, patient-derived, orthotopic xenograft (PDOX) nude mouse models.
Methods. After confirmation of tumor engraftment, mice were randomized to two groups: bright light surgery (BLS)-only and BLS + PIT. Each treatment arm consisted of seven tumor-bearing mice. BLS was performed under standard bright-field with an MVX10 long-working distance, high-magnification microscope on all mice. For BLS + PIT, anti-CEA antibody conjugated with IR700 (anti-CEA-IR700) (50 mu g) was injected intravenously in all mice 24 h before surgery. After the surgery, the resection bed was then irradiated with a red-light-emitting diode at 690 +/- 5 nm with a power density of 150 mW/cm(2).
Results. Anti-CEA-IR700 labelled and illuminated the pancreatic cancer PDOX. Minimal residual cancer of the PDOX was detected by fluorescence after BLS. The local recurrence rate was 85.7 % for BLS-only and 28.6 % for BLS + PIT-treated mice (p = 0.05). The average recurrent tumor weight was 1149.0 +/- 794.6 mg for BLS-only and 210.8 +/- 336.9 mg for BLS + PIT-treated mice (p = 0.015).
Conclusion. Anti-CEA-IR700 was able to label and illuminate a pancreatic cancer PDOX nude mouse model sufficiently for PIT. PIT reduced recurrence by eliminating remaining residual cancer cells after BLS.
C1 [Hiroshima, Yukihiko; Maawy, Ali; Hoffman, Robert M.; Bouvet, Michael] Univ Calif San Diego, Moores Canc Ctr, Dept Surg, San Diego, CA 92103 USA.
[Hiroshima, Yukihiko; Zhang, Yong; Hoffman, Robert M.] AntiCanc Inc, San Diego, CA USA.
[Hiroshima, Yukihiko; Tanaka, Kuniya; Endo, Itaru] Yokohama City Univ, Grad Sch Med, Yokohama, Kanagawa 232, Japan.
[Guzman, Miguel Garcia; Heim, Roger; Makings, Lew] Aspyrian Therapeut Inc, San Diego, CA USA.
[Luiken, George A.] OncoFluor Inc, San Diego, CA USA.
[Kobayashi, Hisataka] NIH, Bethesda, MD 20892 USA.
[Bouvet, Michael] VA San Diego Healthcare Syst, San Diego, CA USA.
RP Hiroshima, Y (reprint author), Univ Calif San Diego, Moores Canc Ctr, Dept Surg, San Diego, CA 92103 USA.
EM mbouvet@ucsd.edu
FU National Cancer Institute [CA132971, 142669]; JSPS KAKENHI [26830081,
26462070, 24592009]
FX This study was supported in part by National Cancer Institute grants
CA132971 and 142669 (to Michael Bouvet and AntiCancer, Inc.) and JSPS
KAKENHI Grant Numbers 26830081 to Yukihiko Hiroshima, 26462070 to Itaru
Endo and 24592009 to Kuniya Tanaka.
NR 17
TC 1
Z9 1
U1 3
U2 9
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 DEC
PY 2015
VL 22
SU 3
BP S1469
EP S1474
DI 10.1245/s10434-015-4553-9
PG 6
WC Oncology; Surgery
SC Oncology; Surgery
GA CZ7OG
UT WOS:000367288100150
PM 25893411
ER
PT J
AU Neychev, V
Steinberg, SM
Yang, LL
Mehta, A
Nilubol, N
Keil, MF
Nieman, L
Stratakis, CA
Kebebew, E
AF Neychev, Vladimir
Steinberg, Seth M.
Yang, Lily
Mehta, Amit
Nilubol, Naris
Keil, Margaret F.
Nieman, Lynnette
Stratakis, Constantine A.
Kebebew, Electron
TI Long-Term Outcome of Bilateral Laparoscopic Adrenalectomy Measured by
Disease-Specific Questionnaire in a Unique Group of Patients with
Cushing's Syndrome
SO ANNALS OF SURGICAL ONCOLOGY
LA English
DT Article
ID QUALITY-OF-LIFE; 100 CONSECUTIVE PROCEDURES; UNILATERAL ADRENALECTOMY;
FOLLOW-UP; CONSENSUS STATEMENT; 10-YEAR EXPERIENCE; HYPERPLASIA;
MANAGEMENT; DIAGNOSIS; TRANSPERITONEAL
AB Background. Laparoscopic bilateral adrenalectomy (LBA) is recommended for patients with bilateral adrenal disease and occult or unresectable ectopic Cushing's syndrome (CS). There are limited data on long-term outcomes after LBA, partly due to the lack of disease-specific tools for the measurement of impact on patients' health and quality of life.
Methods. We used a disease-specific questionnaire covering all major clinicopathologic characteristics of CS. We compared the outcome from LBA to a control group of 60 patients who had thyroidectomy (matched for age, gender, and time of surgery, 2: 1 control-to-CS).
Results. Twenty-eight patients (20 women and 8 men) underwent LBA for CS. Of them, 24 patients (86 %) provided responses to our questionnaire. Ninety-two percent of patients' responses indicated a significant improvement of general Cushing's physical features with complete resolution reported in 59 % of responses. Significant improvement of associated biochemical abnormalities and comorbidities was reported in 83 % of patients' responses including complete reversal in 58 %. Significant improvement in emotional-behavioral symptoms was reported in 84 % of patients' responses with complete recovery in 53 %. All patients expressed satisfaction with LBA and significant improvement in their general health and selfreported quality of life. All of the improvements after LBA were statistically significant compared with the control group.
Conclusions. Our disease-specific questionnaire enables a clearer understanding of the association between the clinical, metabolic, and emotional-behavioral features of CS, its treatment with LBA, and long-term impact on patient-reported quality of life. This disease-specific questionnaire may be useful for future studies in patients with CS.
C1 [Neychev, Vladimir; Yang, Lily; Mehta, Amit; Nilubol, Naris; Kebebew, Electron] NCI, Endocrine Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Steinberg, Seth M.] NCI, Biostat & Data Management Sect, NIH, Bethesda, MD 20892 USA.
[Keil, Margaret F.; Stratakis, Constantine A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrinol & Genet, NIH, Bethesda, MD USA.
[Nieman, Lynnette] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Reprod Endocrinol, NIH, Bethesda, MD USA.
RP Neychev, V (reprint author), NCI, Endocrine Oncol Branch, NIH, Bethesda, MD 20892 USA.
EM vladimir.neychev@nih.gov
FU NIH [NCT00005927, NCT01005654, NCT02001051]
FX The study was supported by the NIH clinical protocols NCT00005927,
NCT01005654, and NCT02001051.
NR 59
TC 2
Z9 2
U1 0
U2 5
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 DEC
PY 2015
VL 22
SU 3
BP S699
EP S706
DI 10.1245/s10434-015-4605-1
PG 8
WC Oncology; Surgery
SC Oncology; Surgery
GA CZ7OG
UT WOS:000367288100057
PM 25968622
ER
PT J
AU Sadowski, SM
Millo, C
Neychev, V
Aufforth, R
Keutgen, X
Glanville, J
Alimchandani, M
Nilubol, N
Herscovitch, P
Quezado, M
Kebebew, E
AF Sadowski, Samira M.
Millo, Corina
Neychev, Vladimir
Aufforth, Rachel
Keutgen, Xavier
Glanville, Joanne
Alimchandani, Meghna
Nilubol, Naris
Herscovitch, Peter
Quezado, Martha
Kebebew, Electron
TI Feasibility of Radio-Guided Surgery with (68)Gallium-DOTATATE in
Patients with Gastro-Entero-Pancreatic Neuroendocrine Tumors
SO ANNALS OF SURGICAL ONCOLOGY
LA English
DT Article
ID SOMATOSTATIN RECEPTOR SCINTIGRAPHY; RADIOGUIDED SURGERY; UNITED-STATES;
MANAGEMENT; GUIDELINES; SYSTEM; EPIDEMIOLOGY; DIAGNOSIS; ENETS; PET
AB Background. Surgery is the only definitive therapy for gastro-entero-pancreatic neuroendocrine tumors (GEP-NETs), and achieving complete tumor resection is an important prognostic factor. Radiopharmaceuticals such as 68 Ga-DOTA peptides have been developed that offer superior accuracy for localization of GEPNETs. The study aim was to determine the feasibility of radio-guided surgery (RGS) using Ga-68-DOTATATE in patients with primary and recurrent GEPNETs
. Methods. Fourteen patients with GEPNETs were enrolled onto a prospective study to determine the feasibility of RGS with Ga-68-DOTATATE. Findings from preoperative imaging, intraoperative exploration, RGS, and pathology were analyzed.
Results. The median decay corrected target count rate was 172.6 (range 28.15-2341) for tumors, with a tumor-to-background ratio (TBR) of 4.46 (range 1.6-43.56). The median lesion size was 1.55 (range 0.5-15) cm. There was no significant correlation between preoperative imaging maximum standardized uptake value (SUVmax) of the lesions and TBR (Spearman r = -0.01, p = 0.9), TBR and tumor size (Spearman r = 0.29, p = 0.14), and SUVmax and tumor size (Spearman r = 0.22, p = 0.28). The probe showed correct identification for gastric and small intestine neuroendocrine tumor (NET), including lymph node metastasis in 17 (81.0 %) of 21 cases, with a median TBR of 3.5 (1.6-40.2). For pancreatic NETs and lymph node metastasis, 16 (66.7 %) of 24 were correctly identified by RGS.
Conclusions. Our study shows that RGS with Ga-68-DOTATATE is feasible and correctly confirms bowel NETs and metastatic mesenteric lymph nodes. Further studies are needed to determine the benefit of RGS with Ga-68-DOTATATE.
C1 [Sadowski, Samira M.; Neychev, Vladimir; Aufforth, Rachel; Keutgen, Xavier; Glanville, Joanne; Nilubol, Naris; Kebebew, Electron] NCI, Endocrine Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Millo, Corina; Herscovitch, Peter] NIH, Positron Emiss Tomog Dept, Warren Grant Magnusson Clin Ctr, Bethesda, MD 20892 USA.
[Alimchandani, Meghna; Quezado, Martha] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA.
RP Sadowski, SM (reprint author), NCI, Endocrine Oncol Branch, NIH, Bethesda, MD 20892 USA.
EM kebebewe@mail.nih.gov
FU Center for Cancer Research, National Cancer Institute
FX We would like to thank Candice Cottle-Delisle, RN, and Roxanne Merkel,
RN, for their help coordinating the clinical protocol and study
subjects; Lily A. Yang for data management; Maureen George for technical
surgical support for the gamma probe; and the staff at the U.S. National
Institutes of Health PET department. This research was supported by the
intramural research programs of the Center for Cancer Research, National
Cancer Institute.
NR 29
TC 1
Z9 1
U1 0
U2 2
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 DEC
PY 2015
VL 22
SU 3
BP S676
EP S682
DI 10.1245/s10434-015-4857-9
PG 7
WC Oncology; Surgery
SC Oncology; Surgery
GA CZ7OG
UT WOS:000367288100054
PM 26350374
ER
PT J
AU Satoh, K
Patel, D
Dieckmann, W
Nilubol, N
Kebebew, E
AF Satoh, Kei
Patel, Dhaval
Dieckmann, William
Nilubol, Naris
Kebebew, Electron
TI Whole Body Metabolic Tumor Volume and Total Lesion Glycolysis Predict
Survival in Patients with Adrenocortical Carcinoma
SO ANNALS OF SURGICAL ONCOLOGY
LA English
DT Article
ID POSITRON-EMISSION-TOMOGRAPHY; ADRENAL INCIDENTALOMAS; PROGNOSTIC VALUE;
MANAGEMENT; PET/CT; DIAGNOSIS; RECURRENT; CANCER; PREVALENCE; MALIGNANCY
AB Background. Adrenocortical carcinoma (ACC) is a rare but lethal malignancy with few reliable prognostic markers. FDG-PET metabolic parameters have been shown to predict survival in several cancers. The objective was to determine if metabolic tumor volume (MTV), total lesion glycolysis (TLG), and maximum standardized uptake value (SUVmax) could serve as prognostic markers in patients with ACC.
Methods. A total of 30 patients with ACC prospectively underwent 18F-FDG PET/CT prior to treatment. Whole body MTV, TLG, and SUVmax were measured by a semiautomatic method. A median cutoff was used to determine an association with overall survival (OS) from the time of 18F-FDG PET/CT by the Kaplan-Meier method.
Results. Patients with high whole body MTV (>87.0 mL), TLG (>229.4 SUVlbm*mL), or SUVmax (>8.9 SUV) had a worse OS compared with those with low whole body MTV (median OS, 24 vs 45.1 months, p < .01), TLG (median OS, 24 vs 40.3 months, p < .005), or SUVmax (median OS, 23.7 vs 35.5 months, p < .02). In patients who had operable disease (n = 23), high whole body MTV (>87.0 mL) and TLG (>229.4 SUVlbm*mL) had a worse OS compared with those with low whole body MTV (median OS, 25.1 vs 45.1 months, p < .05) and TLG (median OS, 25.1 vs 40.3 months, p < .05), but a high SUVmax (>8.9 SUV) was not associated with worse OS (p = .11).
Conclusions. Patients with ACC and a high whole body MTV, TLG, and SUVmax have a worse prognosis and OS. Measurement of whole body MTV and TLG may be helpful for guiding therapy for patients with ACC.
C1 [Satoh, Kei; Patel, Dhaval; Nilubol, Naris; Kebebew, Electron] NCI, Endocrine Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Satoh, Kei] Icahn Sch Med Mt Sinai, New York, NY 10029 USA.
[Dieckmann, William] NIH, Ctr Clin, PET Dept, Bethesda, MD 20892 USA.
RP Satoh, K (reprint author), NCI, Endocrine Oncol Branch, NIH, Bethesda, MD 20892 USA.
EM divot999@gmail.com
OI Patel, Dhaval/0000-0002-5744-568X
FU Center for Cancer Research, National Cancer Institute, National
Institutes of Health; National Institutes of Health (NIH); NIH; Pfizer
Inc.; Doris Duke Charitable Foundation; Newport Foundation; American
Association for Dental Research; Howard Hughes Medical Institute;
Colgate-Palmolive Company
FX This research was supported by the intramural research program of the
Center for Cancer Research, National Cancer Institute, National
Institutes of Health and the National Institutes of Health (NIH) Medical
Research Scholars Program, a public-private partnership supported
jointly by the NIH and generous contributions to the Foundation for the
NIH from Pfizer Inc., The Doris Duke Charitable Foundation, The Newport
Foundation, The American Association for Dental Research, The Howard
Hughes Medical Institute, and the Colgate-Palmolive Company, as well as
other private donors. For a complete list, please visit the Foundation
website at:
http://fnih.org/work/education-training-0/medical-research-scholars-prog
ram.
NR 34
TC 1
Z9 1
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 DEC
PY 2015
VL 22
SU 3
BP S714
EP S720
DI 10.1245/s10434-015-4813-8
PG 7
WC Oncology; Surgery
SC Oncology; Surgery
GA CZ7OG
UT WOS:000367288100059
PM 26282908
ER
PT J
AU Dunleavy, K
AF Dunleavy, Kieron
TI Aggressive B cell Lymphoma: Optimal Therapy for MYC-positive,
Double-Hit, and Triple-Hit DLBCL
SO CURRENT TREATMENT OPTIONS IN ONCOLOGY
LA English
DT Review
DE Double-hit; MYC; BCL2; BCL6; Double-expresser; DA-EPOCH-R
ID RITUXIMAB PLUS CYCLOPHOSPHAMIDE; BURKITT-LYMPHOMA; GERMINAL CENTER;
GENE-EXPRESSION; PROGNOSTIC-SIGNIFICANCE; MOLECULAR SUBTYPES;
ANTITUMOR-ACTIVITY; PREDICTS SURVIVAL; POOR-PROGNOSIS; PHASE-II
AB Approximately 10 % of cases of diffuse large B cell lymphoma (DLBCL) harbor a MYC rearrangement and this has been associated with an inferior outcome following standard therapy across many different studies. Double-hit and triple-hit lymphomas harbor concurrent rearrangements of MYC and BCL2 and/or BCL6 and are also associated with a very aggressive course and poor clinical outcome. It is unclear and there is lack of consensus on how these diseases should be approached therapeutically. They are characterized typically by high tumor proliferation and likely require Burkitt lymphoma-type strategies and several retrospective studies suggest that more intensive approaches than rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) may be beneficial. One challenge in this respect is that most patients with these diseases are older than 60 years and generally have poor tolerability of regimens typically used in Burkitt lymphoma. Dose-adjusted EPOCH-R is an alternative effective immunochemotherapy platform for DLBCL and is effective in Burkitt lymphoma, and retrospective studies suggest that it is effective and feasible in patients with DLBCL that harbors a MYC rearrangement with or without a BCL-2 translocation (double-hit). A multicenter study of this approach in MYC-rearranged DLBCL is ongoing and preliminary results are very encouraging. There is a lack of consensus on the role of consolidation stem cell transplantation in patients who achieve a good response to initial therapy but at this point in time, no (retrospective) studies have demonstrated any benefit. These diseases are also associated with a high rate of CNS involvement and progression and checking for cerebrospinal fluid by cytology and flow cytometry at initial diagnosis should be considered. In summary, based on retrospective data and preliminary prospective data (as more mature data is awaited), while Burkitt-type regimens may be feasible in young patients, DA-EPOCH-R is a reasonable approach for patients with these diseases, particularly for those over the age of 60 years. CNS prophylaxis is a reasonable consideration (depending on clinical characteristics) given that the rate of CNS progression is high. Many exciting new small molecule inhibitors such as BCL-2 and MYC inhibitors are in development and are exciting for these diseases and attempts are underway to combine them with effective immunochemotherapy platforms.
C1 [Dunleavy, Kieron] NCI, Lymphoid Malignancies Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Dunleavy, K (reprint author), NCI, Lymphoid Malignancies Branch, Ctr Canc Res, Bldg 10,Room 4N-115,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM dunleavk@mail.nih.gov
FU National Cancer Institute
FX This work was supported by the intramural program of the National Cancer
Institute.
NR 56
TC 9
Z9 9
U1 3
U2 12
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1527-2729
EI 1534-6277
J9 CURR TREAT OPTION ON
JI Curr. Treat. Options Oncol.
PD DEC
PY 2015
VL 16
IS 12
AR 58
DI 10.1007/s11864-015-0374-0
PG 11
WC Oncology
SC Oncology
GA DA0VS
UT WOS:000367516300004
PM 26634708
ER
PT J
AU Caglayan, M
Wilson, SH
AF Caglayan, Melike
Wilson, Samuel H.
TI Reprint of "Oxidant and environmental toxicant-induced effects
compromise DNA ligation during base excision DNA repair"
SO DNA REPAIR
LA English
DT Article
DE Base excision repair (BER); DNA polymerase beta (pol beta); DNA ligase;
8-oxo-7,8-dihydro-2 '-deoxyguanosine (8-oxoG); Ligation failure;
Abortive ligation products
ID STRAND BREAK REPAIR; TEMPLATING 8-OXOGUANINE LESION; POLYMERASE
ACTIVE-SITE; ABASIC SITES; APURINIC/APYRIMIDINIC ENDONUCLEASE-1;
NEURODEGENERATIVE DISEASE; APRATAXIN DEFICIENCY; CATALYTIC MECHANISM; AP
ENDONUCLEASE-1; OXIDATIVE DAMAGE
AB DNA lesions arise from many endogenous and environmental agents, and such lesions can promote deleterious events leading to genomic instability and cell death. Base excision repair (BER) is the main DNA repair pathway responsible for repairing single strand breaks, base lesions and abasic sites in mammalian cells. During BER, DNA substrates and repair intermediates are channeled from one step to the next in a sequential fashion so that release of toxic repair intermediates is minimized. This includes handoff of the product of gap-filling DNA synthesis to the DNA ligation step. The conformational differences in DNA polymerase beta (pol beta) associated with incorrect or oxidized nucleotide (8-oxodGMP) insertion could impact channeling of the repair intermediate to the final step of BER, i.e., DNA ligation by DNA ligase I or the DNA Ligase III/XRCC1 complex. Thus, modified DNA ligase substrates produced by faulty pol beta gap-filling could impair coordination between pol beta and DNA ligase. Ligation failure is associated with 5'-AMP addition to the repair intermediate and accumulation of strand breaks that could be more toxic than the initial DNA lesions. Here, we provide an overview of the consequences of ligation failure in the last step of BER. We also discuss DNA-end processing mechanisms that could play roles in reversal of impaired BER. Published by Elsevier B.V.
C1 [Caglayan, Melike; Wilson, Samuel H.] NIEHS, Genome Integr & Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA.
RP Wilson, SH (reprint author), NIEHS, Genome Integr & 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, Z01-ES050159]
FX This research was supported by grants Z01-ES050158 and Z01-ES050159 from
the Intramural Research Program of the NIH, National Institute of
Environmental Health Sciences.
NR 73
TC 2
Z9 3
U1 0
U2 6
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 DEC
PY 2015
VL 36
SI SI
BP 86
EP 90
DI 10.1016/j.dnarep.2015.11.002
PG 5
WC Genetics & Heredity; Toxicology
SC Genetics & Heredity; Toxicology
GA DA0MT
UT WOS:000367491900014
PM 26596511
ER
PT J
AU Sun, X
Yang, HW
Sturgill, D
Oliver, B
Rabinow, L
Samson, ML
AF Sun, Xia
Yang, Haiwang
Sturgill, David
Oliver, Brian
Rabinow, Leonard
Samson, Marie-Laure
TI Sxl-Dependent, tra/tra2-Independent Alternative Splicing of the
Drosophila melanogaster X-Linked Gene found in neurons
SO G3-GENES GENOMES GENETICS
LA English
DT Article
DE Sex lethal; found in neurons; alternative splicing; sex-specific
regulation
ID RNA-SEQ DATA; DOSAGE COMPENSATION; SEXUAL-DIFFERENTIATION;
MESSENGER-RNA; BINDING PROTEIN; SOMATIC TISSUES; LETHAL; EXPRESSION;
SWITCH; TRANSCRIPTS
AB Somatic sexual determination and behavior in Drosophila melanogaster are under the control of a genetic cascade initiated by Sex lethal (Sxl). In the female soma, SXL RNA-binding protein regulates the splicing of transformer (tra) transcripts into a female-specific form. The RNA-binding protein TRA and its cofactor TRA2 function in concert in females, whereas SXL, TRA, and TRA2 are thought to not function in males. To better understand sex-specific regulation of gene expression, we analyzed male and female head transcriptome datasets for expression levels and splicing, quantifying sex-biased gene expression via RNA-Seq and qPCR. Our data uncouple the effects of Sxl and tra/tra2 in females in the-sex-biased alternative splicing of head transcripts from the X-linked locus found in neurons (fne), encoding a pan-neuronal RNA-binding protein of the ELAV family. We show that FNE protein levels are downregulated by Sxl in female heads, also independently of tra/tra2. We argue that this regulation may have important sexually dimorphic consequences for the regulation of nervous system development or function.
C1 [Sun, Xia; Rabinow, Leonard; Samson, Marie-Laure] Univ Paris 11, Ctr Neurosci Paris Sud, UMR 8195, F-91405 Orsay, France.
[Sun, Xia; Rabinow, Leonard; Samson, Marie-Laure] Univ Paris 11, CNRS UMR 8195, F-91405 Orsay, France.
[Yang, Haiwang; Sturgill, David; Oliver, Brian] NIDDK, NIH, Bethesda, MD 20892 USA.
[Sturgill, David] Univ Maryland, Program Computat Biol Bioinformat & Gen, College Pk, MD 20742 USA.
RP Samson, ML (reprint author), Univ Paris 11, Ctr Neurosci Paris Sud, CNRS, UMR 8195, Batiment 442 Bis, F-91405 Orsay, France.
EM Marie-Laure.Samson@u-psud.fr
FU Indo-French Center for the Promotion of Advanced Research (IFCPAR)
[4903A]; Universite Paris Sud; Centre National de la Recherche
Scientifique (CNRS); Intramural Research Program of the National
Institute of Diabetes and Digestive and Kidney Diseases at NIH (NIDDK);
China Scholarship Council
FX We thank Tom Cline for constructive criticisms of a prior version of the
manuscript and for kindly providing the Sxl mutant stocks. More stocks
were graciously provided by William Mattox, Bruce Baker, Trudy Mackay,
the Indiana University Drosophila stock center, and the Drosophila
Genetic Resource Center, Kyoto, Japan. We thank Karine Tuphile for
cloning and sequencing of fne cDNAs and Bernadette Wiszniowski for
assistance with stocks. We particularly thank S. Bate for providing the
InVivoStat software. Financial support was provided to M.-L. S. and L.R.
by the Indo-French Center for the Promotion of Advanced Research
(IFCPAR, award #4903A), the Universite Paris Sud, and the Centre
National de la Recherche Scientifique (CNRS). This work was supported in
part by the Intramural Research Program of the National Institute of
Diabetes and Digestive and Kidney Diseases at NIH (NIDDK, to B.O.). X.S.
was supported by a graduate fellowship from the China Scholarship
Council. This work was submitted as a partial requirement for completion
of a doctoral thesis (by X.S.).
NR 57
TC 1
Z9 1
U1 4
U2 6
PU GENETICS SOCIETY AMERICA
PI BETHESDA
PA 9650 ROCKVILLE AVE, BETHESDA, MD 20814 USA
SN 2160-1836
J9 G3-GENES GENOM GENET
JI G3-Genes Genomes Genet.
PD DEC
PY 2015
VL 5
IS 12
BP 2865
EP 2874
DI 10.1534/g3.115.023721
PG 10
WC Genetics & Heredity
SC Genetics & Heredity
GA CZ7CM
UT WOS:000367257500034
PM 26511498
ER
PT J
AU Lingala, S
Ghany, MG
AF Lingala, Shilpa
Ghany, Marc G.
TI Natural History of Hepatitis C
SO GASTROENTEROLOGY CLINICS OF NORTH AMERICA
LA English
DT Article
DE Natural history; Hepatitis C virus; Chronic hepatitis C; Fibrosis;
Cirrhosis; Decompensated liver disease
ID HUMAN-IMMUNODEFICIENCY-VIRUS; LONG-TERM TREATMENT; NUTRITION EXAMINATION
SURVEY; TYPE-2 DIABETES-MELLITUS; GENOME-WIDE ASSOCIATION; LIVER-RELATED
MORTALITY; UNITED-STATES COHORT; BODY-MASS INDEX;
HEPATOCELLULAR-CARCINOMA; FIBROSIS PROGRESSION
AB Hepatitis C infection is a common cause of cirrhosis and indication for liver transplantation in the United States. The incidence of chronic hepatitis C has been declining, but rates of cirrhosis and hepatocellular carcinoma are projected to increase. The outcome of chronic hepatitis C is variable. It is estimated that 20% to 25% will develop cirrhosis over a 25-year to 30-year period. The rate of disease progression is influenced by many host, viral, and environmental factors. Few can be modified.
C1 [Lingala, Shilpa; Ghany, Marc G.] NIDDKD, Liver Dis Branch, NIH, Bethesda, MD 20892 USA.
RP Ghany, MG (reprint author), NIDDKD, Liver Dis Branch, NIH, Bldg 10,Room 9B-16,10 Ctr Dr,MSC 1800, Bethesda, MD 20892 USA.
EM marcg@intra.niddk.nih.gov
FU National Institute of Diabetes and Digestive and Kidney Diseases,
National Institutes of Health [ZIA DK075009 09]
FX This work was supported by the Intramural Program of the National
Institute of Diabetes and Digestive and Kidney Diseases, National
Institutes of Health (ZIA DK075009 09).
NR 128
TC 9
Z9 9
U1 2
U2 5
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0889-8553
EI 1558-1942
J9 GASTROENTEROL CLIN N
JI Gastroenterol. Clin. North Am.
PD DEC
PY 2015
VL 44
IS 4
BP 717
EP +
DI 10.1016/j.gtc.2015.07.003
PG 19
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA CZ8PG
UT WOS:000367361000004
PM 26600216
ER
PT J
AU Maholmes, V
AF Maholmes, Valerie
TI Championing research on traumatised and injured children
SO INJURY PREVENTION
LA English
DT Editorial Material
C1 [Maholmes, Valerie] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD 20852 USA.
RP Maholmes, V (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD 20852 USA.
EM maholmev@mail.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 1
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 1353-8047
EI 1475-5785
J9 INJURY PREV
JI Inj. Prev.
PD DEC
PY 2015
VL 21
IS 6
BP 441
EP 441
DI 10.1136/injuryprev-2015-041881
PG 1
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA DA0GF
UT WOS:000367474900014
PM 26609060
ER
PT J
AU Lau, AF
Fahle, GA
Kemp, MA
Jassem, AN
Dekker, JP
Frank, KM
AF Lau, Anna F.
Fahle, Gary A.
Kemp, Margaret A.
Jassem, Agatha N.
Dekker, John P.
Frank, Karen M.
TI Clinical Performance of Check-Direct CPE, a Multiplex PCR for Direct
Detection of bla(KPC), bla(NDM) and/or bla(VIM), and bla(OXA-48) from
Perirectal Swabs
SO JOURNAL OF CLINICAL MICROBIOLOGY
LA English
DT Article
ID CARBAPENEMASE-PRODUCING ENTEROBACTERIACEAE; REAL-TIME PCR; GRAM-NEGATIVE
BACILLI; RESISTANT ENTEROBACTERIACEAE; RAPID DETECTION; RECTAL SWABS;
CHROMAGAR KPC; MEDIA; ASSAY; SURVEILLANCE
AB We evaluated the clinical performance of Check-Direct CPE for carbapenemase detection directly from 301 perirectal swabs (258 patients) in a nonoutbreak setting. Culture of a PCR-confirmed, carbapenemase-containing organism, or history of colonization with such organism within the previous 2 weeks, was used as the reference standard. Check-Direct CPE demonstrated a sensitivity value, specificity value, positive predictive value (PPV), and negative predictive value (NPV) of 100% (all bla(KPC)), 88%, 21%, and 100%, respectively. False positives accounted for 79% (n = 34) of samples for which a cycle threshold (C-T) value was reached. Simulated studies to evaluate specimen pooling as an approach to minimize costs showed no difference in C-T values for pooled groups of three or five that each contained a single specimen spiked with similar to 1,500 CFU bla(KPC) Klebsiella pneumoniae; however, the detection rate dropped to 60% at a seeded concentration of similar to 150 CFU. When data were pooled, C-T values for bla(KPC) were higher for heavy-feces-containing than for light-feces-containing liquid-suspended specimens. Furthermore, C-T values for liquid-suspended specimens were 4 to 5 C-T values lower (i.e., represented greater sensitivity) than those seen in direct swab analysis. Culture was equivalent to or better than Check-Direct CPE for 13/15 (87%) isolates tested in a limit-of-detection analysis. Detection of a carbapenemase gene at a C-T cutoff value of <= 35 was culture confirmed in 23/24 (96%) of cases; however, C-T values of >35 overlapped broadly between culture-positive (n = 21) and culture-negative (n = 36) specimens. Check-Direct CPE will likely prove most useful in high-prevalence areas or in outbreak settings where rapid carbapenemase detection is critical for infection control management.
C1 [Lau, Anna F.; Fahle, Gary A.; Kemp, Margaret A.; Jassem, Agatha N.; Dekker, John P.; Frank, Karen M.] NIH, Microbiol Serv, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA.
RP Lau, AF (reprint author), NIH, Microbiol Serv, Dept Lab Med, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA.
EM Anna.Lau@nih.gov
FU Intramural Research Program of the National Institutes of Health
FX This work was supported by the Intramural Research Program of the
National Institutes of Health. The content is solely our responsibility
and does not represent the official views of the National Institutes of
Health.
NR 33
TC 6
Z9 6
U1 0
U2 2
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0095-1137
EI 1098-660X
J9 J CLIN MICROBIOL
JI J. Clin. Microbiol.
PD DEC
PY 2015
VL 53
IS 12
BP 3729
EP 3737
DI 10.1128/JCM.01921-15
PG 9
WC Microbiology
SC Microbiology
GA DA1CB
UT WOS:000367532800006
PM 26338860
ER
PT J
AU Hussam, A
Hong, J
AF Hussam, Abul
Hong, Jinsoo
TI A novel field deployable filter paper based amperometric gas sensor for
the measurement of arsenic in water
SO JOURNAL OF ELECTROANALYTICAL CHEMISTRY
LA English
DT Article
DE Arsenic; Arsine; Groundwater; Amperometry; Electrochemical sensor
ID PHASE CHEMI-LUMINESCENCE; DRINKING-WATER; CHEMILUMINESCENCE;
SPECTROMETRY; GROUNDWATER; ANALYZER; SAMPLES; ARSINE; OZONE; GOLD
AB The presence of toxic levels of inorganic arsenic in drinking water is a worldwide problem. Measurement of millions of samples in the field for arsenic is an analytical challenge and the first step to solve the problem. Here, we developed a novel electrochemical arsine sensor and system based on the cell: C(s)/I3-I2, AsH3(g/aq)//I-3(-), I-2 AgI(s)/Ag(s), where I-3(-)/I-2 mediated AsH3(g/l) oxidation which occurred on the C(s) electrode. The sensor system requires 50 mu L of 10 mM iodine solution and a small piece of filter paper placed inside a novel electrochemical cell. The cell exhibited highly efficient arsine mass transport with a limit of detection of 15 mu g/L As(III) in water. A mathematical model of mass transfer of AsH3(g/aq) and following electrochemical reaction was developed and applied to explain the experimental data. Groundwater samples containing arsenic were measured to prove its utility in a field deployable instrument Published by Elsevier B.V.
C1 [Hussam, Abul; Hong, Jinsoo] George Mason Univ, Dept Chem & Biochem, Ctr Clean Water & Sustainable Technol, Fairfax, VA 22030 USA.
RP Hong, J (reprint author), NIMH, PET Radiochem, NIH, Bldg 10,Room B3C355, Bethesda, MD 20892 USA.
EM jinsoohong@mail.nih.gov
NR 20
TC 1
Z9 1
U1 5
U2 18
PU ELSEVIER SCIENCE SA
PI LAUSANNE
PA PO BOX 564, 1001 LAUSANNE, SWITZERLAND
SN 1572-6657
EI 1873-2569
J9 J ELECTROANAL CHEM
JI J. Electroanal. Chem.
PD DEC 1
PY 2015
VL 758
BP 156
EP 162
DI 10.1016/j.jelechem.2015.10.007
PG 7
WC Chemistry, Analytical; Electrochemistry
SC Chemistry; Electrochemistry
GA CZ7KN
UT WOS:000367278400021
ER
PT J
AU Miyake, S
Wakita, H
Bernstock, JD
Castri, P
Ruetzler, C
Miyake, J
Lee, YJ
Hallenbeck, JM
AF Miyake, Shin-ichi
Wakita, Hideaki
Bernstock, Joshua D.
Castri, Paola
Ruetzler, Christl
Miyake, Junko
Lee, Yang-ja
Hallenbeck, John M.
TI Hypophosphorylation of ribosomal protein S6 is a molecular mechanism
underlying ischemic tolerance induced by either hibernation or
preconditioning.
SO JOURNAL OF NEUROCHEMISTRY
LA English
DT Article
DE hibernation; ischemic tolerance; protein translation; ribosomal protein
S6; rpS6 kinase
ID MAMMALIAN TARGET; CEREBRAL-ISCHEMIA; GROUND-SQUIRRELS; INFARCT VOLUME;
RAPAMYCIN MTOR; P70S6 KINASE; PHOSPHORYLATION; TRANSLATION; BRAIN;
IDENTIFICATION
AB Thirteen-lined ground squirrels (Ictidomys tridecemlineatus) have an extraordinary capacity to withstand prolonged and profound reductions in blood flow and oxygen delivery to the brain without incurring any cellular damage. As such, the hibernation torpor of I. tridecemlineatus provides a valuable model of tolerance to ischemic stress. Herein, we report that during hibernation torpor, a marked reduction in the phosphorylation of the ribosomal protein S6 (rpS6) occurs within the brains of I. tridecemlineatus. Of note, rpS6 phosphorylation was shown to increase in the brains of rats that underwent an occlusion of the middle cerebral artery. However, such an increase was attenuated after the implementation of an ischemic preconditioning paradigm. In addition, cultured cortical neurons treated with the rpS6 kinase (S6K) inhibitors, nglucosamine or PF4708671, displayed a decrease in rpS6 phosphorylation and a subsequent increase in tolerance to oxygen/glucose deprivation, an in vitro model of ischemic stroke. Collectively, such evidence suggests that the downregulation of rpS6 signal transduction may account for a substantial part of the observed increase in cellular tolerance to brain ischemia that occurs during hibernation torpor and after ischemic preconditioning. Further identification and characterization of the mechanisms used by hibernating species to increase ischemic tolerance may eventually clarify how the loss of homeostatic control that occurs during and after cerebral ischemia in the clinic can ultimately be minimized and/or prevented.
C1 [Miyake, Shin-ichi; Wakita, Hideaki; Bernstock, Joshua D.; Castri, Paola; Ruetzler, Christl; Miyake, Junko; Lee, Yang-ja; Hallenbeck, John M.] NINDS, Stroke Branch, NIH, Bethesda, MD 20892 USA.
RP Hallenbeck, JM (reprint author), NINDS, Stroke Branch, NIH, Bldg10 Rm5B02,MSC 1401,10 Ctr Dr, Bethesda, MD 20892 USA.
EM hallenbj@ninds.nih.gov
FU Intramural Research Program of the NINDS/NIH
FX This work was supported by the Intramural Research Program of the
NINDS/NIH. The authors declare no competing financial interests.
NR 46
TC 2
Z9 2
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0022-3042
EI 1471-4159
J9 J NEUROCHEM
JI J. Neurochem.
PD DEC
PY 2015
VL 135
IS 5
BP 943
EP 957
DI 10.1111/jnc.13368
PG 15
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA CZ6DN
UT WOS:000367191500010
PM 26375300
ER
PT J
AU Zand, R
Male, S
Lynch, JK
AF Zand, Ramin
Male, Shailesh
Lynch, John K.
TI Diffuse Fluid-Attenuated Inversion Recovery Hyperintensity in
Subarachnoid Space Following Cerebral Angiography and Intravenous
Thrombolysis
SO JOURNAL OF STROKE & CEREBROVASCULAR DISEASES
LA English
DT Article
DE Cortical; blindness; angiography; magnetic resonance imaging
ID TRANSIENT CORTICAL BLINDNESS; BLOOD-BRAIN-BARRIER; CORONARY-ANGIOGRAPHY;
CONTRAST; MRI
AB Objective: Transient cortical blindness (TCB) is a relatively rare but well-recognized complication following cardiovascular and cerebral angiography. Methods: A 68-year-old male developed TCB following cerebral angiography along with punctate diffusion lesion evident on emergent magnetic resonance imaging (MRI). The patient received intravenous tissue plasminogen activator (IV-tPA) for suspected stroke. Results: Follow-up MRI revealed diffuse hyperintensities in subarachnoid space in fluid-attenuated inversion recovery (FLAIR) sequence mostly in bilateral occipital lobes. Conclusion: The finding on the FLAIR as described in this case is an indication of diffuse disruption of the blood-brain barrier perhaps secondary to cerebral angiography, high blood pressure, and IV-tPA. To the best of our knowledge, this is the first reported case of TCB with diffuse postcontrast FLAIR changes.
C1 [Zand, Ramin; Lynch, John K.] NINDS, Sect Stroke Diagnost & Therapeut, Bethesda, MD 20892 USA.
[Male, Shailesh] Univ Tennessee, Ctr Hlth Sci, Dept Neurol, Memphis, TN 38163 USA.
RP Zand, R (reprint author), NINDS, Stroke Branch, NIH, Stroke Program, 10 Ctr Dr,Room B1D-733, Bethesda, MD 20892 USA.
EM ramin.zand@gmail.com
OI Zand, Ramin/0000-0002-9477-0094
NR 10
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1052-3057
EI 1532-8511
J9 J STROKE CEREBROVASC
JI J. Stroke Cerebrovasc. Dis.
PD DEC
PY 2015
VL 24
IS 12
BP E1
EP E3
DI 10.1016/j.jstrokecerebrovasdis.2015.08.021
PG 3
WC Neurosciences; Peripheral Vascular Disease
SC Neurosciences & Neurology; Cardiovascular System & Cardiology
GA CZ8ZY
UT WOS:000367388800001
PM 26476586
ER
PT J
AU Shetty, V
Harrell, L
Murphy, DA
Vitero, S
Gutierrez, A
Belin, TR
Dye, BA
Spolsky, VW
AF Shetty, Vivek
Harrell, Lauren
Murphy, Debra A.
Vitero, Steven
Gutierrez, Alexis
Belin, Thomas R.
Dye, Bruce A.
Spolsky, Vladimir W.
TI Dental disease patterns in methamphetamine users Findings in a large
urban sample
SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION
LA English
DT Article
DE Dental disease; methamphetamine use; patterns; severity
ID EXAMINATION SURVEY NHANES; ORAL-HEALTH COMPONENT; QUALITY-ASSURANCE;
NATIONAL-HEALTH; METH-MOUTH; UNITED-STATES; ROOT CARIES; PREVALENCE;
PERIODONTITIS; POPULATION
AB Background. The authors used a large community sample of methamphetamine (MA) users to verify the patterns and severity of dental disease and establish a hierarchy of caries susceptibility by tooth type and tooth surface.
Methods. Using a stratified sampling approach, 571 MA users received comprehensive oral examinations and psychosocial assessments. Three calibrated dentists characterized dental and periodontal disease by using National Health and Nutrition Examination Survey protocols. The authors also collected data on substance use history and other attributes linked to dental disease.
Results. On all dental outcome measures, MA users evidenced high dental and periodontal disease, with older (>= 30 years) and moderate or heavy MA users disproportionately affected. Women had higher rates of tooth loss and caries, as well as a greater prevalence of anterior caries. Current cigarette smokers were more likely to manifest 5 or more anterior surfaces with untreated caries and 3 or more teeth with root caries. Nearly 3% were edentulous, and a significant percentage (40%) indicated embarrassment with their dental appearance.
Conclusions. MA users have high rates of dental and periodontal disease and manifest a dose-response relationship, with greater levels of MA use associated with higher rates of dental disease. Women and current cigarette smokers are affected disproportionately. The intraoral patterns and hierarchy of caries susceptibility in MA users are distinctive.
Practical Implications. The prevalence and patterns of dental and periodontal disease could be used to alert dentists to possible covert MA use and to plan treatment. Concerns about dental appearance have potential as triggers for behavioral interventions.
C1 [Shetty, Vivek] Univ Calif Los Angeles, Sch Dent, UCLA Ctr Hlth Sci 230009, Los Angeles, CA 90095 USA.
[Harrell, Lauren; Gutierrez, Alexis; Spolsky, Vladimir W.] Univ Calif Los Angeles, Sch Dent, Los Angeles, CA 90095 USA.
[Harrell, Lauren; Belin, Thomas R.] Univ Calif Los Angeles, Dept Biostat, Fielding Sch Publ Hlth, Los Angeles, CA 90095 USA.
[Murphy, Debra A.] Univ Calif Los Angeles, Integrated Subst Abuse Programs, Los Angeles, CA 90095 USA.
[Vitero, Steven] AIDS Project Los Angeles, Dent Serv, Los Angeles, CA USA.
[Dye, Bruce A.] Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA.
RP Shetty, V (reprint author), Univ Calif Los Angeles, Sch Dent, UCLA Ctr Hlth Sci 230009, 10833 Le Conte Ave, Los Angeles, CA 90095 USA.
EM vshetty@ucla.edu
FU National Institutes of Health, National Institute on Drug Abuse [R01
DA026014]; National Institutes of Health, University of California, Los
Angeles Clinical and Translational Science Institute grant [UL1TR000124]
FX This study was funded by the National Institutes of Health, National
Institute on Drug Abuse (R01 DA026014) (V.S.), which had no role in the
design of the study; in the collection, analysis, and interpretation of
data; or in the writing of the report. Additional support for Dr. Belin
was provided by a National Institutes of Health, University of
California, Los Angeles Clinical and Translational Science Institute
grant (UL1TR000124). The findings and conclusions in this report are
those of the authors and do not necessarily represent the views of the
National Institute on Drug Abuse or the National Institutes of Health.
NR 48
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U1 0
U2 4
PU AMER DENTAL ASSOC
PI CHICAGO
PA 211 E CHICAGO AVE, CHICAGO, IL 60611 USA
SN 0002-8177
EI 1943-4723
J9 J AM DENT ASSOC
JI J. Am. Dent. Assoc.
PD DEC
PY 2015
VL 146
IS 12
BP 875
EP 885
DI 10.1016/j.adaj.2015.09.012
PG 11
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA CZ8KB
UT WOS:000367347500021
PM 26610832
ER
PT J
AU Hall, KD
AF Hall, Kevin D.
TI Prescribing low-fat diets: useless for long-term weight loss?
SO LANCET DIABETES & ENDOCRINOLOGY
LA English
DT Editorial Material
ID ENERGY-INTAKE; ACCURATE
C1 [Hall, Kevin D.] NIDDK, Bethesda, MD 20892 USA.
RP Hall, KD (reprint author), NIDDK, Bethesda, MD 20892 USA.
EM kevinh@niddk.nih.gov
FU Intramural NIH HHS
NR 10
TC 0
Z9 0
U1 4
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 2213-8587
J9 LANCET DIABETES ENDO
JI Lancet Diabetes Endocrinol.
PD DEC
PY 2015
VL 3
IS 12
BP 920
EP 921
DI 10.1016/S2213-8587(15)00413-1
PG 3
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA CZ8ZM
UT WOS:000367387600007
PM 26527510
ER
PT J
AU Baird, NJ
Inglese, J
Ferre-D'Amare, AR
AF Baird, Nathan J.
Inglese, James
Ferre-D'Amare, Adrian R.
TI Rapid RNA-ligand interaction analysis through high-information content
conformational and stability landscapes
SO NATURE COMMUNICATIONS
LA English
DT Article
ID DI-GMP RIBOSWITCH; ANTIBACTERIAL DRUG TARGETS; 16S RIBOSOMAL-RNA;
PROTEIN INTERACTIONS; RESPONSE REGULATOR; SMALL MOLECULES; BINDING;
RIBOZYME; ANTIBIOTICS; RECOGNITION
AB The structure and biological properties of RNAs are a function of changing cellular conditions, but comprehensive, simultaneous investigation of the effect of multiple interacting environmental variables is not easily achieved. We have developed an efficient, high-throughput method to characterize RNA structure and thermodynamic stability as a function of multiplexed solution conditions using Forster resonance energy transfer (FRET). In a single FRET experiment using conventional quantitative PCR instrumentation, 19,400 conditions of MgCl2, ligand and temperature are analysed to generate detailed empirical conformational and stability landscapes of the cyclic diguanylate (c-di-GMP) riboswitch. The method allows rapid comparison of RNA structure modulation by cognate and non-cognate ligands. Landscape analysis reveals that kanamycin B stabilizes a non-native, idiosyncratic conformation of the riboswitch that inhibits c-di-GMP binding. This demonstrates that allosteric control of folding, rather than direct competition with cognate effectors, is a viable approach for pharmacologically targeting riboswitches and other structured RNA molecules.
C1 [Baird, Nathan J.; Ferre-D'Amare, Adrian R.] NHLBI, NIH, Bethesda, MD 20892 USA.
[Inglese, James] NIH, Natl Ctr Adv Translat Sci, Rockville, MD 20850 USA.
RP Baird, NJ (reprint author), Univ Sci, Dept Chem & Biochem, 600 South 43rd St, Philadelphia, PA 19104 USA.
EM n.baird@usciences.edu
FU National Heart, Lung and Blood Institute, NIH; National Center for
Advancing Translational Sciences, NIH; Director's Challenge Innovation
Award, NIH; K22 NHLBI Career Transition Award [K22-HL121113A]
FX We thank J. Hogg for use of the microplate fluorometer; T. Christopher
and R. Bonasio for use of qPCR instrumentation for single-fluorophore
control experiments; P. Berget for use of the microplate fluorometer for
single-fluorophore control experiments, G. Piszczek for support with ITC
and initial fluorescence experiments; R. Macarthur for discussions
aiding data analysis; Y.-X. Wang and X. Zuo for experimental SAXS beam
time and support, respectively; and J. Zhang, M. Lau, C. Jones and S.
Bachas for insightful comments. This work was supported by the
intramural programmes of the National Heart, Lung and Blood Institute,
NIH and the National Center for Advancing Translational Sciences, NIH
and a 2013 Director's Challenge Innovation Award, NIH. N.J.B. is a
recipient of a K22 NHLBI Career Transition Award (K22-HL121113A).
NR 55
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U1 5
U2 17
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 DEC
PY 2015
VL 6
AR 8898
DI 10.1038/ncomms9898
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DA1WO
UT WOS:000367586600001
PM 26638992
ER
PT J
AU Jiang, CT
Xie, C
Lv, Y
Li, J
Krausz, KW
Shi, JM
Brocker, CN
Desai, D
Amin, SG
Bisson, WH
Liu, YL
Gavrilova, O
Patterson, AD
Gonzalez, FJ
AF Jiang, Changtao
Xie, Cen
Lv, Ying
Li, Jing
Krausz, Kristopher W.
Shi, Jingmin
Brocker, Chad N.
Desai, Dhimant
Amin, Shantu G.
Bisson, William H.
Liu, Yulan
Gavrilova, Oksana
Patterson, Andrew D.
Gonzalez, Frank J.
TI Intestine-selective farnesoid X receptor inhibition improves
obesity-related metabolic dysfunction
SO NATURE COMMUNICATIONS
LA English
DT Article
ID BILE-ACID; BEIGE FAT; INSULIN-RESISTANCE; GLUCOSE-HOMEOSTASIS;
ENERGY-EXPENDITURE; ADIPOSE-TISSUE; BROWN ADIPOCYTES; MURICHOLIC ACID;
LIVER; MICE
AB The farnesoid X receptor (FXR) regulates bile acid, lipid and glucose metabolism. Here we show that treatment of mice with glycine-beta-muricholic acid (Gly-MCA) inhibits FXR signalling exclusively in intestine, and improves metabolic parameters in mouse models of obesity. Gly-MCA is a selective high-affinity FXR inhibitor that can be administered orally and prevents, or reverses, high-fat diet-induced and genetic obesity, insulin resistance and hepatic steatosis in mice. The high-affinity FXR agonist GW4064 blocks Gly-MCA action in the gut, and intestine-specific Fxr-null mice are unresponsive to the beneficial effects of Gly-MCA. Mechanistically, the metabolic improvements with Gly-MCA depend on reduced biosynthesis of intestinal-derived ceramides, which directly compromise beige fat thermogenic function. Consequently, ceramide treatment reverses the action of Gly-MCA in high-fat diet-induced obese mice. We further show that FXR signalling in ileum biopsies of humans positively correlates with body mass index. These data suggest that Gly-MCA may be a candidate for the treatment of metabolic disorders.
C1 [Jiang, Changtao; Xie, Cen; Krausz, Kristopher W.; Shi, Jingmin; Brocker, Chad N.; Gonzalez, Frank J.] NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Jiang, Changtao; Lv, Ying] Peking Univ, Sch Basic Med Sci, Dept Physiol & Pathophysiol, Beijing 100191, Peoples R China.
[Jiang, Changtao; Lv, Ying] Minist Educ, Key Lab Mol Cardiovasc Sci, Beijing 100191, Peoples R China.
[Li, Jing; Liu, Yulan] Peking Univ, Peoples Hosp, Dept Gastroenterol, Beijing 100044, Peoples R China.
[Desai, Dhimant; Amin, Shantu G.] Penn State Univ, Coll Med, Dept Pharmacol, Hershey, PA 17033 USA.
[Bisson, William H.] Oregon State Univ, Dept Environm & Mol Toxicol, Corvallis, OR 97331 USA.
[Gavrilova, Oksana] NIAID, Mouse Metab Core Lab, NIH, Bethesda, MD 20892 USA.
[Patterson, Andrew D.] Penn State Univ, Dept Vet & Biomed Sci, University Pk, PA 16802 USA.
[Patterson, Andrew D.] Penn State Univ, Ctr Mol Toxicol & Carcinogenesis, University Pk, PA 16802 USA.
RP Patterson, AD (reprint author), Penn State Univ, Dept Vet & Biomed Sci, University Pk, PA 16802 USA.
EM adp117@psu.edu; gonzalef@mail.nih.gov
RI Patterson, Andrew/G-3852-2012
OI Patterson, Andrew/0000-0003-2073-0070
FU Intramural Research Program, Center for Cancer Research, National Cancer
Institute, National Institutes of Health; National Institutes of
Environmental Health Sciences [ES022186]; National Natural Science
Foundation of China [31401011, 81200626]; Pennsylvania Department of
Health using Tobacco CURE Funds
FX We thank Linda G. Byrd and John Buckley for technical assistance with
the mouse studies. We thank Paul A. Dawson, Makoto Miyazaki and Kristina
Schoonjans for recombinant plasmids and Jerry T. Thompson for assistance
with the FXR reporter assays. This work was supported by the Intramural
Research Program, Center for Cancer Research, National Cancer Institute,
National Institutes of Health, and by the National Institutes of
Environmental Health Sciences (ES022186 (A.D.P.)). This project was
funded in part by grants from the National Natural Science Foundation of
China (31401011 to C.J. and 81200626 to J.L.) and in part by a grant
with the Pennsylvania Department of Health using Tobacco CURE Funds (to
A.D.P.). The Pennsylvania Department of Health specifically disclaims
responsibility for any analyses, interpretations or conclusions of this
work.
NR 57
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U1 14
U2 23
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 DEC
PY 2015
VL 6
AR 10166
DI 10.1038/ncomms10166
PG 18
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DA1RT
UT WOS:000367573900001
PM 26670557
ER
PT J
AU Macpherson, LJ
Zaharieva, EE
Kearney, PJ
Alpert, MH
Lin, TY
Turan, Z
Lee, CH
Gallio, M
AF Macpherson, Lindsey J.
Zaharieva, Emanuela E.
Kearney, Patrick J.
Alpert, Michael H.
Lin, Tzu-Yang
Turan, Zeynep
Lee, Chi-Hon
Gallio, Marco
TI Dynamic labelling of neural connections in multiple colours by
trans-synaptic fluorescence complementation
SO NATURE COMMUNICATIONS
LA English
DT Article
ID IN-VIVO; DROSOPHILA BRAIN; PROTEIN; CIRCUITS; SYSTEMS; PHOTORECEPTORS;
CONNECTOMICS; LOCALIZATION; TEMPERATURE; SYNAPSES
AB Determining the pattern of activity of individual connections within a neural circuit could provide insights into the computational processes that underlie brain function. Here, we develop new strategies to label active synapses by trans-synaptic fluorescence complementation in Drosophila. First, we demonstrate that a synaptobrevin-GRASP chimera functions as a powerful activity-dependent marker for synapses in vivo. Next, we create cyan and yellow variants, achieving activity-dependent, multi-colour fluorescence reconstitution across synapses (X-RASP). Our system allows for the first time retrospective labelling of synapses (rather than whole neurons) based on their activity, in multiple colours, in the same animal. As individual synapses often act as computational units in the brain, our method will promote the design of experiments that are not possible using existing techniques. Moreover, our strategies are easily adaptable to circuit mapping in any genetic system.
C1 [Macpherson, Lindsey J.; Turan, Zeynep] Columbia Univ, Howard Hughes Med Inst, New York, NY 10032 USA.
[Macpherson, Lindsey J.; Turan, Zeynep] Columbia Univ, Dept Biochem & Mol Biophys, New York, NY 10032 USA.
[Zaharieva, Emanuela E.; Kearney, Patrick J.; Alpert, Michael H.; Gallio, Marco] Northwestern Univ, Dept Neurobiol, Evanston, IL 60208 USA.
[Lin, Tzu-Yang; Lee, Chi-Hon] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Neuronal Connect, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA.
RP Gallio, M (reprint author), Northwestern Univ, Dept Neurobiol, Evanston, IL 60208 USA.
EM marco.gallio@northwestern.edu
OI Kearney, Patrick/0000-0002-7145-5964; Gallio, Marco/0000-0003-2132-0639
FU NIH [RC1NS069014, R01NS076774, R01NS086859]; Eunice Kennedy Shriver
National Institute of Child Health and Human Development [Z01-HD008776];
Intramural Research Programs of the NIH; [T32HL007909]
FX This work was initially conceived and carried out in the laboratory of
Charles Zuker, supported by NIH grants RC1NS069014 and R01NS076774. Work
in the Gallio Lab was supported by NIH grant R01NS086859 to M.G.
Additional support: the Intramural Research Programs of the NIH and the
Eunice Kennedy Shriver National Institute of Child Health and Human
Development (grant Z01-HD008776 to C.-H.L.). L.J.M. was a fellow of the
Jane Coffin Childs Foundation. M.H.A. is supported by training grant
T32HL007909. We thank Charles Zuker for experimental suggestions,
discussions and support. We thank A. Kuang, M. Schmidt and B. Dick, HHMI
EXROP students C. Washington and C. Gonzalez, summer intern M.
Morgenstern for technical help, I. de la Rosa for fly maintenance and R.
Barretto for insightful comments.
NR 38
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U1 5
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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 DEC
PY 2015
VL 6
AR 10024
DI 10.1038/ncomms10024
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DA1UQ
UT WOS:000367581400001
PM 26635273
ER
PT J
AU Sun, B
Pandey, M
Inman, JT
Yang, Y
Kashlev, M
Patel, SS
Wang, MD
AF Sun, Bo
Pandey, Manjula
Inman, James T.
Yang, Yi
Kashlev, Mikhail
Patel, Smita S.
Wang, Michelle D.
TI T7 replisome directly overcomes DNA damage
SO NATURE COMMUNICATIONS
LA English
DT Article
ID SINGLE-STRANDED-DNA; REPLICATION FORK; ESCHERICHIA-COLI; BACTERIOPHAGE
T7; HELICASE PROTEINS; RNA-POLYMERASE; CIS-SYN; MOLECULES;
PHOTOPRODUCTS; PROCESSIVITY
AB Cells and viruses possess several known 'restart' pathways to overcome lesions during DNA replication. However, these 'bypass' pathways leave a gap in replicated DNA or require recruitment of accessory proteins, resulting in significant delays to fork movement or even cell division arrest. Using single-molecule and ensemble methods, we demonstrate that the bacteriophage T7 replisome is able to directly replicate through a leading-strand cyclobutane pyrimidine dimer (CPD) lesion. We show that when a replisome encounters the lesion, a substantial fraction of DNA polymerase (DNAP) and helicase stay together at the lesion, the replisome does not dissociate and the helicase does not move forward on its own. The DNAP is able to directly replicate through the lesion by working in conjunction with helicase through specific helicase-DNAP interactions. These observations suggest that the T7 replisome is fundamentally permissive of DNA lesions via pathways that do not require fork adjustment or replisome reassembly.
C1 [Sun, Bo; Inman, James T.; Yang, Yi; Wang, Michelle D.] Cornell Univ, Dept Phys, Lab Atom & Solid State Phys, Ithaca, NY 14853 USA.
[Sun, Bo; Inman, James T.; Yang, Yi; Wang, Michelle D.] Cornell Univ, Howard Hughes Med Inst, Ithaca, NY 14853 USA.
[Sun, Bo] ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China.
[Pandey, Manjula; Patel, Smita S.] Rutgers Robert Wood Johnson Med Sch, Dept Biochem & Mol Biol, Piscataway, NJ 08854 USA.
[Kashlev, Mikhail] NCI Ctr Canc Res, Frederick, MD 21702 USA.
RP Wang, MD (reprint author), Cornell Univ, Dept Phys, Lab Atom & Solid State Phys, Ithaca, NY 14853 USA.
EM mwang@physics.cornell.edu
FU National Institutes of Health [GM059849, GM55310]; National Science
Foundation [MCB-0820293]
FX We thank members of the Wang laboratory for critical reading of the
manuscript. We wish to acknowledge support from the National Institutes
of Health grants (GM059849 to M.D.W. and GM55310 to S.S.P.) and the
National Science Foundation grant (MCB-0820293 to M.D.W.).
NR 50
TC 5
Z9 5
U1 0
U2 5
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 DEC
PY 2015
VL 6
AR 10260
DI 10.1038/ncomms10260
PG 8
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA DA1VN
UT WOS:000367583700001
PM 26675048
ER
PT J
AU Li, NZ
An, L
Shen, J
AF Li, Ningzhi
An, Li
Shen, Jun
TI Spectral fitting using basis set modified by measured B-0 field
distribution
SO NMR IN BIOMEDICINE
LA English
DT Article
DE metabolite quantification; non-linear fitting; field map; prefrontal
lobe; deep brain gray matter
ID MAGNETIC-RESONANCE-SPECTROSCOPY; ACETYL-ASPARTYL-GLUTAMATE; ECHO TIME
OPTIMIZATION; DISORDER PATIENTS; METABOLITE CONCENTRATIONS; PREFRONTAL
CORTEX; BIPOLAR DISORDER; HUMAN BRAIN; IN-VIVO; H-1 MRS
AB This study sought to demonstrate and evaluate a novel spectral fitting method to improve quantification accuracy in the presence of large magnetic field distortion, especially with high fields. MRS experiments were performed using a point-resolved spectroscopy (PRESS)-type sequence at 7 T. A double-echo gradient echo (GRE) sequence was used to acquire B-0 maps following MRS experiments. The basis set was modified based on the measured B-0 distribution within the MRS voxel. Quantification results were obtained after fitting the measured MRS data using the modified basis set. The proposed method was validated using numerical Monte Carlo simulations, phantom measurements, and comparison of occipital lobe MRS measurements under homogeneous and inhomogeneous magnetic field conditions. In vivo results acquired from voxels placed in thalamus and prefrontal cortex regions close to the frontal sinus agreed well with published values. Instead of noise-amplifying complex division, the proposed method treats field variations as part of the signal model, thereby avoiding inherent statistical bias associated with regularization. Simulations and experiments showed that the proposed approach reliably quantified results in the presence of relatively large magnetic field distortion. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.
C1 [Li, Ningzhi; An, Li; Shen, Jun] NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA.
RP Li, NZ (reprint author), NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA.
EM ymlnz2008@gmail.com
FU Intramural NIH HHS [Z99 MH999999, ZIA MH002803-12]
NR 26
TC 0
Z9 0
U1 0
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0952-3480
EI 1099-1492
J9 NMR BIOMED
JI NMR Biomed.
PD DEC
PY 2015
VL 28
IS 12
BP 1707
EP 1715
DI 10.1002/nbm.3430
PG 9
WC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy
SC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy
GA CZ7XX
UT WOS:000367315100011
PM 26503305
ER
PT J
AU Bai, RL
Klausc, A
Bellay, T
Stewart, C
Pajevic, S
Nevo, U
Merkle, H
Plenz, D
Basser, PJ
AF Bai, Ruiliang
Klausc, Andreas
Bellay, Tim
Stewart, Craig
Pajevic, Sinisa
Nevo, Uri
Merkle, Hellmut
Plenz, Dietmar
Basser, Peter J.
TI Simultaneous calcium fluorescence imaging and MR of ex vivo organotypic
cortical cultures: a new test bed for functional MRI
SO NMR IN BIOMEDICINE
LA English
DT Article
DE MRI; functional MRI; calcium; fluorescence; BOLD; organotypic culture;
brain; neuronal activity
ID MAGNETIC-RESONANCE MICROSCOPY; NEAR-INFRARED SPECTROSCOPY; HIPPOCAMPAL
SLICE MODEL; NEURONAL-ACTIVITY; HUMAN BRAIN; WATER DIFFUSION; IN-VITRO;
SENSORY STIMULATION; OXYGENATION CHANGES; RAT NEOCORTEX
AB Recently, several new functional (f)MRI contrast mechanisms including diffusion, phase imaging, proton density, etc. have been proposed to measure neuronal activity more directly and accurately than blood-oxygen-level dependent (BOLD) fMRI. However, these approaches have proved difficult to reproduce, mainly because of the dearth of reliable and robust test systems to vet and validate them. Here we describe the development and testing of such a test bed for non-BOLD fMRI. Organotypic cortical cultures were used as a stable and reproducible biological model of neuronal activity that shows spontaneous activity similar to that of in vivo brain cortex without any hemodynamic confounds. An open-access, single-sided magnetic resonance (MR) "profiler" consisting of four permanent magnets with magnetic field of 0.32 T was used in this study to perform MR acquisition. A fluorescence microscope with long working distance objective was mounted on the top of a custom-designed chamber that keeps the organotypic culture vital, and the MR system was mounted on the bottom of the chamber to achieve real-time simultaneous calcium fluorescence optical imaging and MR acquisition on the same specimen. In this study, the reliability and performance of the proposed test bed were demonstrated by a conventional CPMG MR sequence acquired simultaneously with calcium imaging, which is a well-characterized measurement of neuronal activity. This experimental design will make it possible to correlate directly the other candidate functional MR signals to the optical indicia of neuronal activity in the future. Copyright (C) 2015 John Wiley & Sons, Ltd.
C1 [Bai, Ruiliang; Basser, Peter J.] NICHD, Sect Tissue Biophys & Biomimet, PPITS, NIH, Bethesda, MD 20892 USA.
[Bai, Ruiliang] Univ Maryland, Inst Phys Sci & Technol, Biophys Program, College Pk, MD 20742 USA.
[Klausc, Andreas; Bellay, Tim; Stewart, Craig; Plenz, Dietmar] NIMH, Sect Crit Brain Dynam, LSN, NIH, Bethesda, MD 20892 USA.
[Pajevic, Sinisa] NIH, Math & Stat Comp Lab, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA.
[Nevo, Uri] Tel Aviv Univ, Dept Biomed Engn, IL-69978 Tel Aviv, Israel.
[Merkle, Hellmut] NINDS, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20892 USA.
RP Basser, PJ (reprint author), 13 South Dr,Bldg 13,Room 3W16, Bethesda, MD 20892 USA.
EM pjbasser@helix.nih.gov
OI Klaus, Andreas/0000-0002-4133-351X
FU Intramural Research Program (IRP) of the Eunice Kennedy Shriver National
Institute of Child Health and Human Development (NICHD), NIH; IRP of
NINDS
FX This work was supported by the Intramural Research Program (IRP) of the
Eunice Kennedy Shriver National Institute of Child Health and Human
Development (NICHD), NIH. Special thanks to Ms. Lynne A. Holtzclaw and
Dr. James T. Russell from the Microscopy and Imaging Core (MIC) Facility
at NICHD, NIH for assistance in immunohistochemistry and confocal
imaging and Ms. L. Salak for editing the manuscript. We are also
grateful to Dr. Alan P. Koretsky from the Laboratory of Functional and
Molecular Imaging at the National Institute of Neurological Disorders
and Stroke (NINDS) for useful discussion and the support from the IRP of
NINDS.
NR 80
TC 2
Z9 2
U1 0
U2 7
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0952-3480
EI 1099-1492
J9 NMR BIOMED
JI NMR Biomed.
PD DEC
PY 2015
VL 28
IS 12
BP 1726
EP 1738
DI 10.1002/nbm.3424
PG 13
WC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy
SC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy
GA CZ7XX
UT WOS:000367315100013
PM 26510537
ER
PT J
AU Kazak, AE
Abrams, AN
Banks, J
Christofferson, J
DiDonato, S
Grootenhuis, MA
Kabour, M
Madan-Swain, A
Patel, SK
Zadeh, S
Kupst, MJ
AF Kazak, Anne E.
Abrams, Annah N.
Banks, Jaime
Christofferson, Jennifer
DiDonato, Stephen
Grootenhuis, Martha A.
Kabour, Marianne
Madan-Swain, Avi
Patel, Sunita K.
Zadeh, Sima
Kupst, Mary Jo
TI Psychosocial Assessment as a Standard of Care in Pediatric Cancer
SO PEDIATRIC BLOOD & CANCER
LA English
DT Article
DE pediatric oncology; psychosocial assessment; screening; standards of
care
ID QUALITY-OF-LIFE; POSTTRAUMATIC STRESS SYMPTOMS;
BONE-MARROW-TRANSPLANTATION; ACUTE LYMPHOBLASTIC-LEUKEMIA; STEM-CELL
TRANSPLANTATION; CHRONIC HEALTH CONDITIONS; CHRONICALLY ILL CHILDREN;
ASSESSMENT-TOOL PAT2.0; YOUNG-ADULT SURVIVORS; LONG-TERM SURVIVORS
AB This paper presents the evidence for a standard of care for psychosocial assessment in pediatric cancer. An interdisciplinary group of investigators utilized EBSCO, PubMed, PsycINFO, Ovid, and Google Scholar search databases, focusing on five areas: youth/family psychosocial adjustment, family resources, family/social support, previous history/premorbid functioning, and family structure/function. Descriptive quantitative studies, systematic reviews, and meta-analyses (n = 149) were reviewed and evaluated using grading of recommendations, assessment development, and evaluation (GRADE) criteria. There is high quality evidence to support a strong recommendation for multifaceted, systematic assessments of psychosocial health care needs of youth with cancer and their families as a standard of care in pediatric oncology. (C) 2015 Wiley Periodicals, Inc.
C1 [Kazak, Anne E.; Christofferson, Jennifer; DiDonato, Stephen] Nemours Childrens Hlth Syst, Ctr Healthcare Delivery Sci, Wilmington, DE USA.
[Kazak, Anne E.; Christofferson, Jennifer; DiDonato, Stephen] Nemours Childrens Hlth Syst, Ctr Pediat Traumat Stress, Wilmington, DE USA.
[Kazak, Anne E.] Thomas Jefferson Univ, Sidney Kimmel Med Coll, Philadelphia, PA 19107 USA.
[Abrams, Annah N.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Abrams, Annah N.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
[Banks, Jaime] Parent Advocate, Bethesda, MD USA.
[Grootenhuis, Martha A.] Univ Amsterdam, Acad Med Ctr, Emma Childrens Hosp, NL-1105 AZ Amsterdam, Netherlands.
[Kabour, Marianne] Transit Profess Ctr, Portland, OR USA.
[Madan-Swain, Avi] Univ Alabama Birmingham, Childrens Alabama, Birmingham, AL USA.
[Patel, Sunita K.] City Hope Med Ctr, Duarte, CA USA.
[Patel, Sunita K.] City Hope Natl Med Ctr, Beckman Res Inst, Duarte, CA 91010 USA.
[Zadeh, Sima] NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA.
[Kupst, Mary Jo] Med Coll Wisconsin, Milwaukee, WI 53226 USA.
RP Kazak, AE (reprint author), AI Du Pont Hosp Children, Nemours Ctr Healthcare Delivery Sci, 1701 Rockland Rd,Suite 160, Wilmington, DE 19803 USA.
EM anne.kazak@nemours.org
FU Mattie Miracle Foundation; National Institutes of Health; Center for
Pediatric Traumatic Stress [U79SM061255]
FX Grant sponsor: Mattie Miracle Foundation; Grant sponsor: National
Institutes of Health and the Center for Pediatric Traumatic Stress;
Grant number: U79SM061255
NR 166
TC 2
Z9 2
U1 5
U2 10
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1545-5009
EI 1545-5017
J9 PEDIATR BLOOD CANCER
JI Pediatr. Blood Cancer
PD DEC
PY 2015
VL 62
SU 5
BP S426
EP +
DI 10.1002/pbc.25730
PG 34
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA CZ7OZ
UT WOS:000367290000003
PM 26700916
ER
PT J
AU Lichtenthal, WG
Sweeney, CR
Roberts, KE
Corner, GW
Donovan, LA
Prigerson, HG
Wiener, L
AF Lichtenthal, Wendy G.
Sweeney, Corinne R.
Roberts, Kailey E.
Corner, Geoffrey W.
Donovan, Leigh A.
Prigerson, Holly G.
Wiener, Lori
TI Bereavement Follow-Up After the Death of a Child as a Standard of Care
in Pediatric Oncology
SO PEDIATRIC BLOOD & CANCER
LA English
DT Article
DE bereaved parents; bereavement; cancer; death of a child; palliative
care; pediatric oncology
ID RANDOMIZED CONTROLLED-TRIAL; PROLONGED GRIEF DISORDER;
MENTAL-HEALTH-SERVICES; OF-LIFE CARE; PALLIATIVE CARE; PARENTAL GRIEF;
SOCIAL SUPPORT; FAMILY PERSPECTIVES; MOTHERS EXPERIENCE; COMPLICATED
GRIEF
AB After a child's death to cancer, families commonly want continued connection with the healthcare team that cared for their child, yet bereavement follow-up is often sporadic. A comprehensive literature search found that many bereaved parents experience poor psychological outcomes during bereavement and that parents want follow-up and benefit from continued connection with their child's healthcare providers. Evidence suggests that the standard of care should consist of at least one meaningful contact between the healthcare team and bereaved parents to identify those at risk for negative psychosocial sequelae and to provide resources for bereavement support. (C) 2015 Wiley Periodicals, Inc.
C1 [Lichtenthal, Wendy G.; Sweeney, Corinne R.; Roberts, Kailey E.; Corner, Geoffrey W.] Mem Sloan Kettering Canc Ctr, Dept Psychiat & Behav Sci, New York, NY 10022 USA.
[Sweeney, Corinne R.] Fairleigh Dickinson Univ, Dept Psychol, Teaneck, NJ USA.
[Corner, Geoffrey W.] Univ So Calif, Dept Psychol, Los Angeles, CA 90089 USA.
[Donovan, Leigh A.] Univ New S Wales, Sch Womens & Childrens Hlth, Sydney, NSW, Australia.
[Prigerson, Holly G.] Weill Cornell Med Coll, Dept Med, New York, NY USA.
[Wiener, Lori] NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA.
RP Lichtenthal, WG (reprint author), Mem Sloan Kettering Canc Ctr, Dept Psychiat & Behav Sci, 641 Lexington Ave,7th Floor, New York, NY 10022 USA.
EM lichtenw@mskcc.org
OI Lichtenthal, Wendy/0000-0003-3597-7826
FU National Cancer Institute (NCI) [K07 CA172216, T32 CA009461]
FX Grant sponsor: National Cancer Institute (NCI); Grant number: K07
CA172216 and T32 CA009461
NR 140
TC 6
Z9 6
U1 5
U2 10
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1545-5009
EI 1545-5017
J9 PEDIATR BLOOD CANCER
JI Pediatr. Blood Cancer
PD DEC
PY 2015
VL 62
SU 5
BP S834
EP +
DI 10.1002/pbc.25700
PG 36
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA CZ7OZ
UT WOS:000367290000016
PM 26700929
ER
PT J
AU Thompson, AL
Christiansen, HL
Elam, M
Hoag, J
Irwin, MK
Pao, M
Voll, M
Noll, RB
Kelly, KP
AF Thompson, Amanda L.
Christiansen, Heather L.
Elam, Megan
Hoag, Jennifer
Irwin, Mary Kay
Pao, Maryland
Voll, Megan
Noll, Robert B.
Kelly, Katherine Patterson
TI Academic Continuity and School Reentry Support as a Standard of Care in
Pediatric Oncology
SO PEDIATRIC BLOOD & CANCER
LA English
DT Article
DE childhood cancer; psychosocial; school reentry
ID CHRONIC HEALTH CONDITIONS; CHILDHOOD-CANCER; REINTEGRATION PROGRAM;
CHRONIC ILLNESS; BRAIN-TUMORS; CHILDREN; SURVIVORS; EDUCATION;
PERCEPTIONS; TEACHERS
AB Clinicians agree that return to school after diagnosis promotes the positive adjustment of children and adolescents with cancer; however, the school reentry process can present challenges. The aim of this review was to critically evaluate the literature on school reentry support for youth with cancer. Seventeen publications were identified. School reentry services were well-received by families and educators; increased teacher and peer knowledge about childhood cancer; influenced peer and educator attitudes toward the patient; and improved communication and collaboration between patients/families, school, and the healthcare team. Evidence supports a strong recommendation for school reentry support for youth with cancer. (C) 2015 Wiley Periodicals, Inc.
C1 [Thompson, Amanda L.] Childrens Natl Hlth Syst, Ctr Canc & Blood Disorders, Washington, DC 20010 USA.
[Christiansen, Heather L.] Blank Childrens Hosp, Canc & Blood Disorders Ctr, Des Moines, IA USA.
[Elam, Megan] Cincinnati Childrens Hosp Med Ctr, Canc & Blood Dis Inst, Cincinnati, OH 45229 USA.
[Hoag, Jennifer] Med Coll Wisconsin, Dept Pediat Hematol Oncol BMT, Milwaukee, WI 53226 USA.
[Irwin, Mary Kay] Nationwide Childrens Hosp, Sch Hlth Serv, Columbus, OH USA.
[Pao, Maryland] NIMH, Bethesda, MD 20892 USA.
[Voll, Megan; Noll, Robert B.] Univ Pittsburgh, Dept Pediat, Pittsburgh, PA 15260 USA.
[Kelly, Katherine Patterson] Childrens Natl Hlth Syst, Dept Nursing Res & Qual Outcomes, Washington, DC USA.
RP Kelly, KP (reprint author), Childrens Natl Hlth Syst, Washington, DC 20010 USA.
EM Kakelly@childrensnational.org
FU Intramural NIH HHS [ZIA MH002922-01]
NR 35
TC 2
Z9 2
U1 2
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1545-5009
EI 1545-5017
J9 PEDIATR BLOOD CANCER
JI Pediatr. Blood Cancer
PD DEC
PY 2015
VL 62
SU 5
BP S805
EP +
DI 10.1002/pbc.25760
PG 13
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA CZ7OZ
UT WOS:000367290000014
PM 26700927
ER
PT J
AU Weaver, MS
Heinze, KE
Kelly, KP
Wiener, L
Casey, RL
Bell, CJ
Wolfe, J
Garee, AM
Watson, A
Hinds, PS
AF Weaver, Meaghann S.
Heinze, Katherine E.
Kelly, Katherine P.
Wiener, Lori
Casey, Robert L.
Bell, Cynthia J.
Wolfe, Joanne
Garee, Amy M.
Watson, Anne
Hinds, Pamela S.
TI Palliative Care as a Standard of Care in Pediatric Oncology
SO PEDIATRIC BLOOD & CANCER
LA English
DT Article
DE communication; family-centered care; palliative care; psychosocial
support; quality of life
ID QUALITY-OF-LIFE; PATIENT-REPORTED OUTCOMES; YOUNG-ADULT ONCOLOGY;
ADVANCED CANCER; BRAIN-TUMORS; CHILDREN; END; DEATH; PARENTS;
PERSPECTIVES
AB The study team conducted a systematic review of pediatric and adolescent palliative cancer care literature from 1995 to 2015 using four databases to inform development of a palliative care psychosocial standard. A total of 209 papers were reviewed with inclusion of 73 papers for final synthesis. Revealed topics of urgent consideration include the following: symptom assessment and intervention, direct patient report, effective communication, and shared decision-making. Standardization of palliative care assessments and interventions in pediatric oncology has the potential to foster improved quality of care across the cancer trajectory for children and adolescents with cancer and their family members. (C) 2015 Wiley Periodicals, Inc.
C1 [Weaver, Meaghann S.] Childrens Natl Hlth Syst, Dept Oncol, Washington, DC USA.
[Weaver, Meaghann S.] St Jude Childrens Res Hosp, Dept Oncol, Memphis, TN 38105 USA.
[Heinze, Katherine E.] Johns Hopkins Univ, Sch Nursing, Baltimore, MD USA.
[Kelly, Katherine P.; Hinds, Pamela S.] Childrens Natl Hlth Syst, Dept Nursing Res & Qual Outcomes, Washington, DC USA.
[Wiener, Lori] NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Casey, Robert L.] Univ Colorado, Childrens Hosp Colorado, Ctr Canc & Blood Disorders, Denver, CO 80202 USA.
[Bell, Cynthia J.] Wayne State Univ, Coll Nursing, Detroit, MI 48202 USA.
[Bell, Cynthia J.] Hosp Michigan Inst, Detroit, MI USA.
[Wolfe, Joanne] Dana Farber Canc Inst, Dept Psychosocial Oncol & Palliat Care, Boston, MA 02115 USA.
[Garee, Amy M.] Nationwide Childrens Hosp, Dept Oncol, Columbus, OH USA.
[Watson, Anne] Childrens Natl Hlth Syst, Dept Crit Care Med, Washington, DC USA.
[Hinds, Pamela S.] George Washington Univ, Dept Pediat, Washington, DC 20052 USA.
RP Weaver, MS (reprint author), St Jude Childrens Res Hosp, 262 Danny Thomas Pl,MS 260, Memphis, TN 38105 USA.
EM Meaghann.Weaver@StJude.org
OI Bell, Cynthia/0000-0002-9026-0986
FU Intramural NIH HHS [Z99 CA999999]
NR 61
TC 4
Z9 4
U1 5
U2 13
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1545-5009
EI 1545-5017
J9 PEDIATR BLOOD CANCER
JI Pediatr. Blood Cancer
PD DEC
PY 2015
VL 62
SU 5
BP S829
EP S833
DI 10.1002/pbc.25695
PG 5
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA CZ7OZ
UT WOS:000367290000015
PM 26700928
ER
PT J
AU Wiener, L
Kazak, AE
Noll, RB
Patenaude, AF
Kupst, MJ
AF Wiener, Lori
Kazak, Anne E.
Noll, Robert B.
Patenaude, Andrea Farkas
Kupst, Mary Jo
TI Interdisciplinary Collaboration in Standards of Psychosocial Care
SO PEDIATRIC BLOOD & CANCER
LA English
DT Editorial Material
C1 [Wiener, Lori] NCI, Pediat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Kazak, Anne E.] Nemours Childrens Hlth Syst, Wilmington, DE USA.
[Kazak, Anne E.] Thomas Jefferson Univ, Sidney Kimmel Med Sch, Philadelphia, PA 19107 USA.
[Noll, Robert B.] Univ Pittsburgh, Dept Pediat, Pittsburgh, PA 15260 USA.
[Patenaude, Andrea Farkas] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
[Kupst, Mary Jo] Med Coll Wisconsin, Dept Pediat, Milwaukee, WI 53226 USA.
RP Wiener, L (reprint author), NCI, Pediat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM wienerl@mail.nih.gov
FU Intramural NIH HHS [Z99 CA999999]
NR 1
TC 1
Z9 1
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1545-5009
EI 1545-5017
J9 PEDIATR BLOOD CANCER
JI Pediatr. Blood Cancer
PD DEC
PY 2015
VL 62
SU 5
BP S425
EP S425
DI 10.1002/pbc.25718
PG 1
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA CZ7OZ
UT WOS:000367290000002
PM 26700915
ER
PT J
AU Wiener, L
Kazak, AE
Noll, RB
Patenaude, AF
Kupst, MJ
AF Wiener, Lori
Kazak, Anne E.
Noll, Robert B.
Patenaude, Andrea Farkas
Kupst, Mary Jo
TI Standards for the Psychosocial Care of Children With Cancer and Their
Families: An Introduction to the Special Issue
SO PEDIATRIC BLOOD & CANCER
LA English
DT Article
DE cancer; child; family; pediatric; psychosocial; standards
ID RECOMMENDATIONS; GUIDELINES; CONSENSUS; ONCOLOGY; GRADE
AB Pediatric oncology psychosocial professionals collaborated with an interdisciplinary group of experts and stakeholders and developed evidence-based standards for pediatric psychosocial care. Given the breadth of research evidence and traditions of clinical care, 15 standards were derived. Each standard is based on a systematic review of relevant literature and used the AGREE II process to evaluate the quality of the evidence. This article describes the methods used to develop the standards and introduces the 15 articles included in this special issue. Established standards help ensure that all children with cancer and their families receive essential psychosocial care. (C) 2015 Wiley Periodicals, Inc.
C1 [Wiener, Lori] NCI, Pediat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Kazak, Anne E.] Thomas Jefferson Univ, Sidney Kimmel Med Sch, Nemours Childrens Hlth Syst, Philadelphia, PA 19107 USA.
[Noll, Robert B.] Univ Pittsburgh, Pittsburgh, PA USA.
[Patenaude, Andrea Farkas] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
[Kupst, Mary Jo] Med Coll Wisconsin, Dept Pediat, Milwaukee, WI 53226 USA.
RP Wiener, L (reprint author), NCI, Pediat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM wienerl@mail.nih.gov
FU Mattie Miracle Cancer Foundation; National Cancer Institute; Center for
Pediatric Traumatic Stress [5U79SM061255-03]
FX Grant sponsor: Mattie Miracle Cancer Foundation; Grant sponsor: National
Cancer Institute; Grant sponsor: Center for Pediatric Traumatic Stress;
Grant number: 5U79SM061255-03
NR 25
TC 7
Z9 7
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1545-5009
EI 1545-5017
J9 PEDIATR BLOOD CANCER
JI Pediatr. Blood Cancer
PD DEC
PY 2015
VL 62
SU 5
BP S419
EP S424
DI 10.1002/pbc.25675
PG 6
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA CZ7OZ
UT WOS:000367290000001
PM 26397836
ER
PT J
AU Goldstein, RB
Smith, SM
Dawson, DA
Grant, BF
AF Goldstein, Rise B.
Smith, Sharon M.
Dawson, Deborah A.
Grant, Bridget F.
TI Sociodemographic and Psychiatric Diagnostic Predictors of 3-Year
Incidence of DSM-IV Substance Use Disorders Among Men and Women in the
National Epidemiologic Survey on Alcohol and Related Conditions
SO PSYCHOLOGY OF ADDICTIVE BEHAVIORS
LA English
DT Article
DE substance use disorders; incidence; predictors; epidemiology; gender
differences
ID GENERAL-POPULATION SAMPLE; AGE-OF-ONSET; UNITED-STATES; CANNABIS USE;
PERSONALITY-DISORDERS; HEALTH SURVEY; RISK-FACTORS; DRUG-USE;
AUDADIS-IV; DEPENDENCE
AB Incidence rates of alcohol and drug use disorders (AUDs and DUDs) are consistently higher in men than women, but information on whether sociodemographic and psychiatric diagnostic predictors of AUD and DUD incidence differ by sex is limited. Using data from Waves 1 and 2 of the National Epidemiologic Survey on Alcohol and Related Conditions, sex-specific 3-year incidence rates of AUDs and DUDs among United States adults were compared by sociodemographic variables and baseline psychiatric disorders. Sex-specific logistic regression models estimated odds ratios for prediction of incident AUDs and DUDs, adjusting for potentially confounding baseline sociodemographic and diagnostic variables. Few statistically significant sex differences in predictive relationships were identified and those observed were generally modest. Prospective research is needed to identify predictors of incident DSM-5 AUDs and DUDs and their underlying mechanisms, including whether there is sex specificity by developmental phase, in the role of additional comorbidity in etiology and course, and in outcomes of prevention and treatment.
C1 [Goldstein, Rise B.; Smith, Sharon M.; Dawson, Deborah A.; Grant, Bridget F.] NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH, Bethesda, MD 20892 USA.
[Dawson, Deborah A.] Kelly Govt Serv, Rockville, MD USA.
RP Goldstein, RB (reprint author), NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH, Room 3071,MS 9304,5635 Fishers Lane, Bethesda, MD 20892 USA.
EM goldster@mail.nih.gov
OI Goldstein, Rise/0000-0002-9603-9473
FU National Institute on Alcohol Abuse and Alcoholism (NIAAA); Intramural
Program of National Institutes of Health, NIAAA
FX The National Epidemiologic Survey on Alcohol and Related Conditions
(NESARC) is funded by the National Institute on Alcohol Abuse and
Alcoholism (NIAAA) with supplemental support from the National Institute
on Drug Abuse. This research was supported in part by the Intramural
Program of the National Institutes of Health, NIAAA. A preliminary
version of parts of this article was presented at the 167th Annual
Meeting of the American Psychiatric Association, May, 2014, New York,
NY. The authors extend their thanks to S. Patricia Chou, PhD, and Tulshi
D. Saha, PhD, for invaluable assistance with the revision of this
article. The views and opinions expressed in this report are those of
the authors and should not be construed to represent the views of
sponsoring organizations, agencies, or the U.S. government.
NR 55
TC 1
Z9 1
U1 3
U2 13
PU EDUCATIONAL PUBLISHING FOUNDATION-AMERICAN PSYCHOLOGICAL ASSOC
PI WASHINGTON
PA 750 FIRST ST, NE, WASHINGTON, DC 20002-4242 USA
SN 0893-164X
EI 1939-1501
J9 PSYCHOL ADDICT BEHAV
JI Psychol. Addict. Behav.
PD DEC
PY 2015
VL 29
IS 4
BP 924
EP 932
DI 10.1037/adb0000080
PG 9
WC Substance Abuse; Psychology, Multidisciplinary
SC Substance Abuse; Psychology
GA DA0BE
UT WOS:000367460900011
PM 26727008
ER
PT J
AU Jang, S
Yu, LR
Abdelmegeed, MA
Gao, Y
Banerjee, A
Song, BJ
AF Jang, Sehwan
Yu, Li-Rong
Abdelmegeed, Mohamed A.
Gao, Yuan
Banerjee, Atrayee
Song, Byoung-Joon
TI Critical role of c-jun N-terminal protein kinase in promoting
mitochondrial dysfunction and acute liver injury
SO REDOX BIOLOGY
LA English
DT Article
DE Acute liver injury; Carbon tetrachloride; JNK; Protein phosphorylation;
Mitochondria; Differential proteomics
ID CARBON-TETRACHLORIDE; RAT-LIVER; JNK INHIBITOR; ACETAMINOPHEN
HEPATOTOXICITY; APOPTOSIS; TOXICITY; TRANSLOCATION; ACTIVATION; ALCOHOL;
DAMAGE
AB The mechanism by which c-Jun N-terminal protein kinase (JNK) promotes tissue injury is poorly understood. Thus we aimed at studying the roles of JNK and its phospho-target proteins in mouse models of acute liver injury. Young male mice were exposed to a single dose of CCl4 (50 mg/kg, IP) and euthanized at different time points. Liver histology, blood alanine aminotransferase, and other enzyme activities were measured in CCl4-exposed mice without or with the highly-specific JNK inhibitors. Phosphoproteins were purified from control or CCl4-exposed mice and analyzed by differential mass-spectrometry followed by further characterizations of immunoprecipitation and activity measurements. JNK was activated within 1 h while liver damage was maximal at 24 h post-CCl4 injection. Markedly increased phosphorylation of many mitochondrial proteins was observed between 1 and 8 h following CCl4 exposure. Pretreatment with the selective JNK inhibitor SU3327 or the mitochondria-targeted antioxidant mito-TEMPO markedly reduced the levels of p-JNK, mitochondrial phosphoproteins and liver damage in CCl4-exposed mice. Differential proteomic analysis identified many phosphorylated mitochondrial proteins involved in anti-oxidant defense, electron transfer, energy supply, fatty acid oxidation, etc. Aldehyde dehydrogenase, NADH-ubiquinone oxidoreductase, and alpha-ketoglutarate dehydrogenase were phosphorylated in CCl4-exposed mice but dephosphorylated after SU3327 pretreatment. Consistently, the suppressed activities of these enzymes were restored by SU3327 pretreatment in CCl4-exposed mice. These data provide a novel mechanism by which JNK, rapidly activated by CCl4, promotes mitochondrial dysfunction and acute hepatotoxicity through robust phosphorylation of numerous mitochondrial proteins. Published by Elsevier B.V.
C1 [Jang, Sehwan; Abdelmegeed, Mohamed A.; Banerjee, Atrayee; Song, Byoung-Joon] NIAAA, Lab Membrane Biochem & Biophys, Bethesda, MD 20892 USA.
[Yu, Li-Rong; Gao, Yuan] US FDA, Biomarkers & Alternat Models Branch, Div Syst Biol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
RP Song, BJ (reprint author), NIAAA, Lab Membrane Biochem & Biophys, Bethesda, MD 20892 USA.
EM sehwan.jang@upr.edu; abdelmegeedm@mail.nih.gov; yuangao2000@gmail.com;
atrayee.liver@gmail.com; bj.song@nih.gov
FU Intramural Research Program of National Institute of Alcohol Abuse and
Alcoholism (NIAAA); Intramural Fund of National Center for Toxicological
Research, U.S. Food and Drug Administration (NCTR/FDA)
FX This study was supported by the Intramural Research Program of National
Institute of Alcohol Abuse and Alcoholism (NIAAA) and in part with funds
from the Intramural Fund of National Center for Toxicological Research,
U.S. Food and Drug Administration (NCTR/FDA). The views presented in
this article do not necessarily reflect those of the U.S. Food and Drug
Administration. The authors are also grateful to Drs. Youngshim Choi and
Klaus Gawrisch for the excellent technical help and support for this
study, respectively.
NR 59
TC 8
Z9 8
U1 0
U2 5
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 2213-2317
J9 REDOX BIOL
JI Redox Biol.
PD DEC
PY 2015
VL 6
BP 552
EP 564
DI 10.1016/j.redox.2015.09.040
PG 13
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA CZ8GR
UT WOS:000367338700054
PM 26491845
ER
PT J
AU Bergman, A
Becher, G
Blumberg, B
Bjerregaard, P
Bornman, R
Brandt, I
Casey, SC
Frouin, H
Giudice, LC
Heindel, JJ
Iguchi, T
Jobling, S
Kidd, KA
Kortenkamp, A
Lind, PM
Muir, D
Ochieng, R
Ropstad, E
Ross, PS
Skakkebaek, NE
Toppari, J
Vandenberg, LN
Woodruff, TJ
Zoeller, RT
AF Bergman, Ake
Becher, Georg
Blumberg, Bruce
Bjerregaard, Poul
Bornman, Riana
Brandt, Ingvar
Casey, Stephanie C.
Frouin, Heloise
Giudice, Linda C.
Heindel, Jerrold J.
Iguchi, Taisen
Jobling, Susan
Kidd, Karen A.
Kortenkamp, Andreas
Lind, P. Monica
Muir, Derek
Ochieng, Roseline
Ropstad, Erik
Ross, Peter S.
Skakkebaek, Niels Erik
Toppari, Jorma
Vandenberg, Laura N.
Woodruff, Tracey J.
Zoeller, R. Thomas
TI Manufacturing doubt about endocrine disrupter science - A rebuttal of
industry-sponsored critical comments on the UNEP/WHO report "State of
the Science of Endocrine Disrupting Chemicals 2012"
SO REGULATORY TOXICOLOGY AND PHARMACOLOGY
LA English
DT Editorial Material
DE Endocrine disruption; EDCs; Endocrine disruptors
ID EPIDEMIOLOGY; FRAMEWORK; CAUSATION; MODE
AB We present a detailed response to the critique of "State of the Science of Endocrine Disrupting Chemicals 2012" (UNEP/WHO, 2013) by financial stakeholders, authored by Lamb et al. (2014). Lamb et al.'s claim that UNEP/WHO (2013) does not provide a balanced perspective on endocrine disruption is based on incomplete and misleading quoting of the report through omission of qualifying statements and inaccurate description of study objectives, results and conclusions. Lamb et al. define extremely narrow standards for synthesizing evidence which are then used to dismiss the UNEP/WHO 2013 report as flawed. We show that Lamb et al. misuse conceptual frameworks for assessing causality, especially the Bradford Hill criteria, by ignoring the fundamental problems that exist with inferring causality from empirical observations. We conclude that Lamb et al.'s attempt of deconstructing the UNEP/WHO (2013) report is not particularly erudite and that their critique is not intended to be convincing to the scientific community, but to confuse the scientific data. Consequently, it promotes misinterpretation of the UNEP/WHO (2013) report by non-specialists, bureaucrats, politicians and other decision makers not intimately familiar with the topic of endocrine disruption and therefore susceptible to false generalizations of bias and subjectivity. (C) 2015 The Authors. Published by Elsevier Inc.
C1 [Bergman, Ake] Swedish Toxicol Sci Res Ctr Swetox, Sodertalje, Sweden.
[Becher, Georg] Norwegian Inst Publ Hlth, Oslo, Norway.
[Blumberg, Bruce; Casey, Stephanie C.] Univ Calif Irvine, Irvine, CA USA.
[Bjerregaard, Poul] Univ Southern Denmark, Odense, Denmark.
[Bornman, Riana] Univ Pretoria, Sch Hlth Syst & Publ Hlth, ZA-0002 Pretoria, South Africa.
[Brandt, Ingvar; Lind, P. Monica] Uppsala Univ, Uppsala, Sweden.
[Frouin, Heloise; Ross, Peter S.] Vancouver Aquarium Marine Sci Ctr, Vancouver, BC, Canada.
[Giudice, Linda C.; Woodruff, Tracey J.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Heindel, Jerrold J.] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA.
[Iguchi, Taisen] Natl Inst Basic Biol, Okazaki, Aichi 444, Japan.
[Jobling, Susan; Kortenkamp, Andreas] Brunel Univ London, Uxbridge, Middx, England.
[Kidd, Karen A.] Univ New Brunswick, New Brunswick, NJ USA.
[Muir, Derek] Environm Canada, Burlington, ON L7R 4A6, Canada.
[Ochieng, Roseline] Aga Khan Univ Hosp, Nairobi, Kenya.
[Ropstad, Erik] Norwegian Univ Life Sci, Oslo, Norway.
[Skakkebaek, Niels Erik] Univ Copenhagen, Copenhagen Univ Hosp, Copenhagen, Denmark.
[Toppari, Jorma] Univ Turku, Turku, Finland.
[Vandenberg, Laura N.; Zoeller, R. Thomas] Univ Massachusetts, Amherst, MA 01003 USA.
RP Bergman, A (reprint author), Swedish Toxicol Sci Res Ctr Swetox, Sodertalje, Sweden.
EM ake.bergman@swetox.se
RI jobling, susan/N-9316-2016;
OI Brandt, Ingvar/0000-0002-5386-2400; Bergman, Ake/0000-0003-3403-093X;
Kidd, Karen/0000-0002-5619-1358; Bjerregaard, Poul/0000-0002-2065-7232
NR 22
TC 8
Z9 8
U1 6
U2 18
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0273-2300
EI 1096-0295
J9 REGUL TOXICOL PHARM
JI Regul. Toxicol. Pharmacol.
PD DEC
PY 2015
VL 73
IS 3
BP 1007
EP 1017
DI 10.1016/j.yrtph.2015.07.026
PG 11
WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology
SC Legal Medicine; Pharmacology & Pharmacy; Toxicology
GA CZ7KX
UT WOS:000367279400042
PM 26239693
ER
PT J
AU Gao, J
Adams, RP
Swain, SM
AF Gao, J.
Adams, R. P.
Swain, S. M.
TI Does CDKN2A loss predict palbociclib benefit?
SO CURRENT ONCOLOGY
LA English
DT Article
DE Medical oncology; breast cancer
ID ADVANCED BREAST-CANCER; KINASE 4/6 INHIBITOR; CDK4; P16
AB Palbociclib, an oral small-molecule inhibitor of cyclin-dependent kinases 4 and 6, was recently approved by the U.S. Food and Drug Administration in combination with letrozole for postmenopausal women with advanced hormone receptor-positive, HER2-negative breast cancer. Patients with loss of CDKN2A (p16), an inherent negative regulator of cyclin-dependent kinases 4 and 6, were not separately studied because of the significant response of the patients selected based only on receptor status. Here, we report a patient with metastatic estrogen receptor-positive, HER2-negative breast cancer with CDKN2A loss who experienced a clinical response to palbociclib.
C1 [Gao, J.] NCI, NIH, Bethesda, MD 20892 USA.
[Adams, R. P.; Swain, S. M.] MedStar Washington Hosp Ctr, Washington Canc Inst, Washington, DC 20010 USA.
RP Swain, SM (reprint author), MedStar Washington Hosp Ctr, Washington Canc Inst, 110 Irving St NW, Washington, DC 20010 USA.
EM sandra.m.swain@medstar.net
OI Swain, Sandra/0000-0002-1320-3830
FU Pfizer; Incyte
FX We have read and understood Current Oncology's policy on disclosing
conflicts of interest, and we declare the following interests: SMS's
institution has received research funding from Pfizer and Incyte. SMS is
also a paid advisory board consultant for Pfizer. The other authors
declare that they have no conflicts of interest. All authors contributed
to the writing and revision of the report and approved the final
version.
NR 13
TC 2
Z9 2
U1 0
U2 2
PU MULTIMED INC
PI TORONTO
PA 66 MARTIN ST, TORONTO, ON L9T 2R2, CANADA
SN 1198-0052
J9 CURR ONCOL
JI Curr. Oncol.
PD DEC
PY 2015
VL 22
IS 6
BP E498
EP E501
DI 10.3747/co.22.2700
PG 4
WC Oncology
SC Oncology
GA CZ3DB
UT WOS:000366983500012
PM 26715889
ER
PT J
AU Natrajan, MS
Komori, M
Kosa, P
Johnson, KR
Wu, TX
Franklin, RJM
Bielekova, B
AF Natrajan, Muktha S.
Komori, Mika
Kosa, Peter
Johnson, Kory R.
Wu, Tianxia
Franklin, Robin J. M.
Bielekova, Bibiana
TI Pioglitazone regulates myelin phagocytosis and multiple sclerosis
monocytes
SO ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY
LA English
DT Article
ID CENTRAL-NERVOUS-SYSTEM; CEREBROSPINAL-FLUID; CNS REMYELINATION;
MACROPHAGE POLARIZATION; INFLAMMATORY RESPONSES; INDUCED DEMYELINATION;
SOLUBLE CD14; MRI ACTIVITY; CELLS; ACTIVATION
AB Objective: Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS). Myeloid phagocytes, including blood monocytes recruited to demyelinating lesions, may play a dual role in MS: on one hand, they might enhance CNS damage after differentiating toward a proinflammatory phenotype; on the other, they promote remyelination and repair through effective phagocytosis of myelin debris. We have previously determined that the retinoid X receptor (RXR) plays an important role in monocyte phagocytosis of myelin. Peroxisome proliferator-activated receptor gamma is an RXR binding partner that plays a key role in myeloid cell biology and is targeted by the thiazolidinedione group of antidiabetics such as pioglitazone. Consequently, the purpose of this study was to determine if monocyte functions and differentiation profiles differ in MS patients compared to healthy volunteers (HV) and whether pioglitazone can reverse these differences to promote CNS recovery. Methods: Monocytes were isolated from MS patients and HV (n >= 36/group), and their ability to phagocytose myelin and modulate inflammation in the presence/absence of 1 mu mol/L pioglitazone (the in vivo achievable concentration) was quantified by flow cytometry, transcriptional profiling, and proteomic assays. Results: MS monocytes display impaired phagocytosis of myelin debris and enhanced proinflammatory differentiation. Pioglitazone treatment causes partial normalization of identified monocyte abnormalities in MS and fully reverses the deficit in myelin phagocytosis. Interpretation: These findings suggest that by inhibiting proinflammatory differentiation of monocytes and enhancing their phagocytosis of myelin, pioglitazone may be a useful adjunct therapy to immunomodulatory agents that target dysregulated adaptive immunity in MS.
C1 [Natrajan, Muktha S.; Komori, Mika; Kosa, Peter; Bielekova, Bibiana] NINDS, Neuroimmunol Dis Unit, NIH, Bethesda, MD 20892 USA.
[Natrajan, Muktha S.; Franklin, Robin J. M.] Univ Cambridge, Wellcome Trust MRC Cambridge Stem Cell Inst, Cambridge CB2 0AH, England.
[Natrajan, Muktha S.; Franklin, Robin J. M.] Univ Cambridge, Dept Clin Neurosci, Cambridge CB2 0AH, England.
[Johnson, Kory R.; Wu, Tianxia] NINDS, NIH, Bethesda, MD 20892 USA.
RP Bielekova, B (reprint author), NINDS, Neuroimmunol Dis Unit, NIH, Bethesda, MD 20892 USA.
EM bibi.bielekova@nih.gov
NR 61
TC 1
Z9 1
U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 2328-9503
J9 ANN CLIN TRANSL NEUR
JI Ann. Clin. Transl. Neurol.
PD DEC
PY 2015
VL 2
IS 12
BP 1071
EP 1084
DI 10.1002/acn3.260
PG 14
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA CZ6WA
UT WOS:000367240500003
PM 26734659
ER
PT J
AU Peng, SY
Xu, JH
Pelkey, KA
Chandra, G
Zhang, ZJ
Bagh, MB
Yuan, XQ
Wu, LG
McBain, CJ
Mukherjee, AB
AF Peng, Shiyong
Xu, Jianhua
Pelkey, Kenneth A.
Chandra, Goutam
Zhang, Zhongjian
Bagh, Maria B.
Yuan, Xiaoqing
Wu, Ling-Gang
McBain, Chris J.
Mukherjee, Anil B.
TI Suppression of agrin-22 production and synaptic dysfunction in Cln1(-/-)
mice
SO ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY
LA English
DT Article
ID NEURONAL CEROID-LIPOFUSCINOSIS; PALMITOYL-PROTEIN THIOESTERASE;
LYSOSOMAL STORAGE DISORDERS; MENTAL-RETARDATION; OXIDATIVE STRESS; MOUSE
MODEL; NERVOUS-SYSTEM; KNOCKOUT MICE; NEUROTRYPSIN; NEUROPATHOLOGY
AB Objective: Oxidative stress in the brain is highly prevalent in many neurodegenerative disorders including lysosomal storage disorders, in which neurodegeneration is a devastating manifestation. Despite intense studies, a precise mechanism linking oxidative stress to neuropathology in specific neurodegenerative diseases remains largely unclear. Methods: Infantile neuronal ceroid lipofuscinosis (INCL) is a devastating neurodegenerative lysosomal storage disease caused by mutations in the ceroid lipofuscinosis neuronal-1 (CLN1) gene encoding palmitoyl-protein thioesterase-1. Previously, we reported that in the brain of Cln1(-/-) mice, which mimic INCL, and in postmortem brain tissues from INCL patients, increased oxidative stress is readily detectable. We used molecular, biochemical, immunohistological, and electrophysiological analyses of brain tissues of Cln1(-/-) mice to study the role(s) of oxidative stress in mediating neuropathology. Results: Our results show that in Cln1(-/-) mice oxidative stress in the brain via upregulation of the transcription factor, CCAAT/enhancer-binding protein-delta, stimulated expression of serpina1, which is an inhibitor of a serine protease, neurotrypsin. Moreover, in the Cln1(-/-) mice, suppression of neurotrypsin activity by serpina1 inhibited the cleavage of agrin (a large proteoglycan), which substantially reduced the production of agrin-22, essential for synaptic homeostasis. Direct whole-cell recordings at the nerve terminals of Cln1(-/-) mice showed inhibition of Ca2+ currents attesting to synaptic dysfunction. Treatment of these mice with a thioesterase-mimetic small molecule, N-tert (Butyl) hydroxylamine (NtBuHA), increased agrin-22 levels. Interpretation: Our findings provide insight into a novel pathway linking oxidative stress with synaptic pathology in Cln1(-/-) mice and suggest that NtBuHA, which increased agrin-22 levels, may ameliorate synaptic dysfunction in this devastating neurodegenerative disease.
C1 [Peng, Shiyong; Chandra, Goutam; Zhang, Zhongjian; Bagh, Maria B.; Mukherjee, Anil B.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Dev Genet, Program Dev Endocrinol & Genet, NIH, Bethesda, MD 20892 USA.
[Xu, Jianhua; Wu, Ling-Gang] NINDS, Synapt Transmiss Sect HNQ23 R, NIH, Bethesda, MD 20892 USA.
[Pelkey, Kenneth A.; Yuan, Xiaoqing; McBain, Chris J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Dev Neurosci, NIH, Bethesda, MD 20892 USA.
RP Mukherjee, AB (reprint author), NIH, Bldg 10,Room 9D42, Bethesda, MD 20892 USA.
EM mukherja@exchange.nih.gov
NR 52
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 2328-9503
J9 ANN CLIN TRANSL NEUR
JI Ann. Clin. Transl. Neurol.
PD DEC
PY 2015
VL 2
IS 12
BP 1085
EP 1104
DI 10.1002/acn3.261
PG 20
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA CZ6WA
UT WOS:000367240500004
PM 26734660
ER
PT J
AU Wang, X
Wang, H
Bi, C
Zhang, X
Huang, X
Zhang, X
Iqbal, J
Wright, GW
Staudt, LM
Chan, WC
McKeithan, TW
Wang, P
Zhang, H
Fu, K
AF Wang, X.
Wang, H.
Bi, C.
Zhang, X.
Huang, X.
Zhang, X.
Iqbal, J.
Wright, G. W.
Staudt, L. M.
Chan, W. C.
McKeithan, T. W.
Wang, P.
Zhang, H.
Fu, K.
TI miR-17 similar to 92 activates the canonical NF-kappa B signaling by
targeting TNFAIP3, CYLD and Rnf11 in ABC-DLBCL lymphoma
SO ANNALS OF ONCOLOGY
LA English
DT Meeting Abstract
CT Asia Congress of the European-Society-for-Medical-Oncology (ESMO)
CY DEC 18-21, 2015
CL Singapore, SINGAPORE
SP European Soc Med Oncol
C1 [Wang, X.; Wang, H.; Wang, P.; Zhang, H.] Tianjin Med Univ, Dept Lymphoma, Canc Inst & Hosp, Tianjin, Peoples R China.
[Bi, C.; Huang, X.; Zhang, X.; Iqbal, J.; Fu, K.] Univ Nebraska Med Ctr, Dept Pathol & Microbiol & Internal Med, Omaha, NE USA.
[Zhang, X.] Chinese Acad Med Sci, Inst Hematol, Dept Pediat, Tianjin, Peoples R China.
[Zhang, X.] Chinese Acad Med Sci, Blood Dis Hosp, Tianjin, Peoples R China.
[Zhang, X.] Peking Union Med Coll, Tianjin, Peoples R China.
[Wright, G. W.] NCI, Biometr Res Branch, Div Canc Treatment & Diag, NIH, Bethlehem, MD USA.
[Staudt, L. M.; Chan, W. C.] NCI, Lymphoid Malignancies Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[McKeithan, T. W.] City Hope Natl Med Ctr, Dept Pathol, Duarte, CA USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0923-7534
EI 1569-8041
J9 ANN ONCOL
JI Ann. Oncol.
PD DEC
PY 2015
VL 26
SU 9
MA 296P
BP 88
EP 88
PG 1
WC Oncology
SC Oncology
GA CZ5RC
UT WOS:000367158700295
ER
PT J
AU Viollet, C
Ragoussis, J
Yarchoan, R
Pezzella, F
AF Viollet, C.
Ragoussis, J.
Yarchoan, R.
Pezzella, F.
TI A whole genome approach to better understand the link between Kaposi's
sarcoma-associated herpesvirus and human cancers
SO ANNALS OF ONCOLOGY
LA English
DT Meeting Abstract
CT Asia Congress of the European-Society-for-Medical-Oncology (ESMO)
CY DEC 18-21, 2015
CL Singapore, SINGAPORE
SP European Soc Med Oncol
C1 [Viollet, C.; Yarchoan, R.] Natl Canc Inst, Ctr Canc Res, Bethesda, MD USA.
[Ragoussis, J.] McGill Univ, Genome Sci, Montreal, PQ, Canada.
[Pezzella, F.] Univ Oxford, John Radcliffe Hosp, RDM Clin Lab Sci, Oxford OX3 9DU, England.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0923-7534
EI 1569-8041
J9 ANN ONCOL
JI Ann. Oncol.
PD DEC
PY 2015
VL 26
SU 9
MA 359O
BP 108
EP 108
PG 1
WC Oncology
SC Oncology
GA CZ5RC
UT WOS:000367158700358
ER
PT J
AU Chen, JF
Xiao, YY
Gai, ZX
Li, R
Zhu, ZX
Bai, CL
Tanguay, RL
Xu, XJ
Huang, CJ
Dong, QX
AF Chen, Jiangfei
Xiao, Yanyan
Gai, Zengxin
Li, Rong
Zhu, Zixu
Bai, Chenglian
Tanguay, Robert L.
Xu, Xiaojiang
Huang, Changjiang
Dong, Qiaoxiang
TI Reproductive toxicity of low level bisphenol A exposures in a
two-generation zebrafish assay: Evidence of male-specific effects
SO AQUATIC TOXICOLOGY
LA English
DT Article
DE Zebrafish; Chronic exposure; BPA; Sperm; Mitochondrial biogenesis; Wnt
signaling
ID MEDAKA ORYZIAS-LATIPES; PIMEPHALES-PROMELAS; PERINATAL EXPOSURE; SEX
DETERMINATION; FATHEAD MINNOW; TERM EXPOSURE; MALE GOLDFISH; SPERM;
QUALITY; DIFFERENTIATION
AB Bisphenol A (BPA), a high-volume chemical used to make polycarbonate plastic and epoxy resins, is a ubiquitous contaminant in environment and human body. To investigate the reproductive effects of longterm exposure to low concentrations of BPA, a two-generation study was conducted using the aquatic model species of zebrafish. Our findings revealed that exposure to 1 nM (0.228 mu g/L) BPA for continuous two generations resulted in female-biased sex ratio in both F1 and F2 adult population, decreased sperm density, and decreased sperm quality as measured by motility, velocity, ATP content and lipid peroxidation in F1 and F2 males. Females were less sensitive to BPA exposures than males as no adverse effects were found in female gonads or gametes. Delayed hatching at 48 hpf and increased malformation and mortality were found in the offspring from BPA exposed F2, but not F1 parents. Most importantly, the adverse effect on larval development and survival from BPA exposed F2 parents was paternal-specific, resulting mainly from BPA exposed males. Subsequent transcription analysis of F2 male gonads revealed dysregulated mitochondrial biogenesis and significant activation of non-canonical Wnt/planar cell polarity and Wnt/Calcium signaling pathways. Gene expression analysis of larvae from BPA exposed F2 parents showed significant reduced expression of DNA methyltransferases such as dnmt1, dnmt3, and dnmt5. In conclusion, low level BPA exposures for continuous two generations not only affects sex ratio and sperm quantity/quality in F1 and F2 adults, reproductive success in offspring from F2 parents, but also perturbs various molecular pathways potentially contributing to these BPA induced male-specific reproductive defects. (C) 2015 Elsevier B.V. All rights reserved.
C1 [Chen, Jiangfei; Xiao, Yanyan; Gai, Zengxin; Li, Rong; Zhu, Zixu; Bai, Chenglian; Huang, Changjiang; Dong, Qiaoxiang] Wenzhou Med Univ, Sch Lab Med & Life Sci, Zhejiang Prov Key Lab Technol & Applicat Model Or, Wenzhou 325035, Peoples R China.
[Chen, Jiangfei; Xiao, Yanyan; Gai, Zengxin; Li, Rong; Zhu, Zixu; Bai, Chenglian; Huang, Changjiang; Dong, Qiaoxiang] Wenzhou Med Univ, Inst Environm Safety & Human Hlth, Wenzhou 325035, Peoples R China.
[Tanguay, Robert L.] Oregon State Univ, Sinnhuber Aquat Res Lab, Environm & Mol Toxicol, Corvallis, OR 97333 USA.
[Tanguay, Robert L.] Oregon State Univ, Environm Hlth Sci Ctr, Corvallis, OR 97333 USA.
[Xu, Xiaojiang] NIEHS, Integrated Bioinformat, Res Triangle Pk, NC 27709 USA.
RP Huang, CJ (reprint author), Wenzhou Med Univ, Sch Lab Med & Life Sci, Zhejiang Prov Key Lab Technol & Applicat Model Or, Wenzhou 325035, Peoples R China.
EM cjhuang5711@163.com; dqxdong@163.com
RI Huang, Changjiang/F-2644-2010; Dong, Qiaoxiang/F-1918-2010
FU National Natural Science Foundation of China [41271491]; National
Environmental Protection Public Welfare Science and Technology Research
Program of China [201309047]
FX This work was supported in part by funding from the National Natural
Science Foundation of China (No. 41271491) and the National
Environmental Protection Public Welfare Science and Technology Research
Program of China (No. 201309047).
NR 51
TC 6
Z9 7
U1 11
U2 49
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0166-445X
EI 1879-1514
J9 AQUAT TOXICOL
JI Aquat. Toxicol.
PD DEC
PY 2015
VL 169
BP 204
EP 214
DI 10.1016/j.aquatox.2015.10.020
PG 11
WC Marine & Freshwater Biology; Toxicology
SC Marine & Freshwater Biology; Toxicology
GA CZ3TV
UT WOS:000367027800021
PM 26562050
ER
PT J
AU Henderson, M
Simeon-Dubach, D
Albert, M
AF Henderson, Marianne
Simeon-Dubach, Daniel
Albert, Monique
TI Finding the Path to Biobank Sustainability Through Sound Business
Planning
SO BIOPRESERVATION AND BIOBANKING
LA English
DT Editorial Material
C1 [Henderson, Marianne] NCI, NIH, Bethesda, MD 20892 USA.
[Simeon-Dubach, Daniel] Medservice, Walchwil, Switzerland.
[Albert, Monique] Ontario Inst Canc Res, Toronto, ON, Canada.
RP Henderson, M (reprint author), NCI, NIH, Bethesda, MD 20892 USA.
EM hendersm@mail.nih.gov
NR 4
TC 6
Z9 6
U1 0
U2 0
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1947-5535
EI 1947-5543
J9 BIOPRESERV BIOBANK
JI Biopreserv. Biobank.
PD DEC 1
PY 2015
VL 13
IS 6
SI SI
BP 385
EP 386
DI 10.1089/bio.2015.29039.mh
PG 2
WC Cell Biology; Chemistry, Applied; Medical Laboratory Technology
SC Cell Biology; Chemistry; Medical Laboratory Technology
GA CZ3MU
UT WOS:000367009000001
PM 26697906
ER
PT J
AU Odeh, H
Miranda, L
Rao, A
Vaught, J
Greenman, H
McLean, J
Reed, D
Memon, S
Fombonne, B
Guan, P
Moore, HM
AF Odeh, Hana
Miranda, Lisa
Rao, Abhi
Vaught, Jim
Greenman, Howard
McLean, Jeffrey
Reed, Daniel
Memon, Sarfraz
Fombonne, Benjamin
Guan, Ping
Moore, Helen M.
TI The Biobank Economic Modeling Tool (BEMT): Online Financial Planning to
Facilitate Biobank Sustainability
SO BIOPRESERVATION AND BIOBANKING
LA English
DT Article
ID BUSINESS MODEL; USER FEES; BIOREPOSITORIES; CHALLENGES; GAP
AB Background: Biospecimens are essential resources for advancing basic and translational research. However, there are little data available regarding the costs associated with operating a biobank, and few resources to enable their long-term sustainability. To support the research community in this effort, the National Institutes of Health, National Cancer Institute's Biorepositories and Biospecimen Research Branch has developed the Biobank Economic Modeling Tool (BEMT). The tool is accessible at http://biospecimens.cancer.gov/resources/bemt.asp. Methods: To obtain market-based cost information and to inform the development of the tool, a survey was designed and sent to 423 biobank managers and directors across the world. The survey contained questions regarding infrastructure investments, salary costs, funding options, types of biospecimen resources and services offered, as well as biospecimen pricing and service-related costs. Results: A total of 106 responses were received. The data were anonymized, aggregated, and used to create a comprehensive database of cost and pricing information that was integrated into the web-based tool, the BEMT. The BEMT was built to allow the user to input cost and pricing data through a seven-step process to build a cost profile for their biobank, define direct and indirect costs, determine cost recovery fees, perform financial forecasting, and query the anonymized survey data from comparable biobanks. Conclusion: A survey was conducted to obtain a greater understanding of the costs involved in operating a biobank. The anonymized survey data was then used to develop the BEMT, a cost modeling tool for biobanks. Users of the tool will be able to create a cost profile for their biobanks' specimens, products and services, establish pricing, and allocate costs for biospecimens based on percent cost recovered, and perform project-specific cost analyses and financial forecasting.
C1 [Odeh, Hana; Rao, Abhi; Vaught, Jim; Memon, Sarfraz; Fombonne, Benjamin; Guan, Ping; Moore, Helen M.] NCI, Biorepositories & Biospecimen Res Branch, Bethesda, MD 20892 USA.
[Odeh, Hana; Fombonne, Benjamin] Kelly Govt Solut, Rockville, MD USA.
[Miranda, Lisa] Biobusiness Consulting Inc, Newburyport, MA USA.
[Vaught, Jim] Gray Sourcing, San Diego, CA USA.
[Greenman, Howard] Provia Labs LLC, Littleton, MA USA.
[McLean, Jeffrey] Leidos Biomed Res Inc, Rockville, MD USA.
[Reed, Daniel] Wrycan Inc, Cambridge, MA USA.
RP Moore, HM (reprint author), NCI, 9609 Med Ctr Dr,3W 428, Rockville, MD 20850 USA.
EM moorehe@mail.nih.gov
FU Biorepositories and Biospecimen Research Branch at the National Cancer
Institute, National Institutes of Health
FX Funding: This project has been funded in whole or in part with federal
funds from the American Recovery and Re-investment Act (ARRA) from the
Biorepositories and Biospecimen Research Branch at the National Cancer
Institute, National Institutes of Health.
NR 19
TC 4
Z9 4
U1 1
U2 4
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1947-5535
EI 1947-5543
J9 BIOPRESERV BIOBANK
JI Biopreserv. Biobank.
PD DEC 1
PY 2015
VL 13
IS 6
SI SI
BP 421
EP 429
DI 10.1089/bio.2015.0089
PG 9
WC Cell Biology; Chemistry, Applied; Medical Laboratory Technology
SC Cell Biology; Chemistry; Medical Laboratory Technology
GA CZ3MU
UT WOS:000367009000006
PM 26697911
ER
PT J
AU Lheureux, S
Oza, AM
Laurie, SA
Halford, R
Jonker, D
Chen, E
Keller, D
Bourade, V
Wang, L
Doyle, L
Siu, LL
Goel, R
AF Lheureux, S.
Oza, A. M.
Laurie, S. A.
Halford, R.
Jonker, D.
Chen, E.
Keller, D.
Bourade, V.
Wang, L.
Doyle, L.
Siu, L. L.
Goel, R.
TI A phase I combination dose-escalation study of eribulin mesylate and
gemcitabine in patients with advanced solid tumours: a study of the
Princess Margaret Consortium
SO BRITISH JOURNAL OF CANCER
LA English
DT Article
DE eribulin; gemcitabine; advanced cancer; phase I; solid tumours; safety;
gynaecological cancer
ID METASTATIC BREAST-CANCER; VIVO ANTICANCER ACTIVITIES; CELL LUNG-CANCER;
HALICHONDRIN-B; ANALOG; E7389; CISPLATIN; MONOTHERAPY; MECHANISMS; VITRO
AB Background: Eribulin mesylate is a synthetic microtubule inhibitor that showed cytotoxic synergy in combination with gemcitabine preclinically. This combination was assessed in a Phase I dose-finding trial in patients diagnosed with advanced solid tumours who had received up to two prior chemotherapy regimens for metastatic disease (CP cohort).
Methods: Dose escalation was performed in a 3+3 design to identify the recommended phase II dose (RP2D). Two additional expansion cohorts in women with gynaecologic cancers at the RP2D (G), and further dose escalation of metastatic chemotherapy-naive patients (CN), were evaluated.
Results: 45 patients were treated: 21 (CP), 10 (G) and 14 (CN). The initial combination of eribulin and gemcitabine was administered on days 1, 8, and 15 of a 28-day cycle; however, due to 2 out of 6 dose-limiting haematological toxicities at the first dose level, a reduced dose-intense schedule was assessed. The RP2D was defined at 1.0mgm(-2) eribulin and 1000mgm(-2) gemcitabine day 1 and 8 q3 weeks. No other significant toxicities were observed in the G expansion cohort. Neutropenia prevented further dose escalation in the CN cohort. Objective responses were seen in all three cohorts -2/21 (CP), 1/10 (G) and 2/14 (CN).
Conclusions: The combination of eribulin and gemcitabine was well tolerated at the RP2D.
C1 [Lheureux, S.; Oza, A. M.; Halford, R.; Chen, E.; Wang, L.; Siu, L. L.] Princess Margaret Canc Ctr, Dept Med Oncol, Toronto, ON M5G 2M9, Canada.
[Laurie, S. A.; Jonker, D.; Keller, D.; Bourade, V.; Goel, R.] Ottawa Hosp Canc Ctr, Dept Med Oncol, Ottawa, ON K1H 8M5, Canada.
[Doyle, L.] NCI, CTEP, Bethesda, MD 20892 USA.
RP Goel, R (reprint author), Ottawa Hosp Canc Ctr, Dept Med Oncol, Ottawa, ON K1H 8M5, Canada.
EM rgoel@toh.on.ca
FU NCI US grant [HHSN261201100032C]
FX We acknowledge the NCI US grant; Contract # HHSN261201100032C.
NR 28
TC 1
Z9 1
U1 1
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 DEC 1
PY 2015
VL 113
IS 11
BP 1534
EP 1540
DI 10.1038/bjc.2015.343
PG 7
WC Oncology
SC Oncology
GA CZ5UL
UT WOS:000367167400002
PM 26554651
ER
PT J
AU Bogdanova, TI
Zurnadzhy, LY
Nikiforov, YE
Leeman-Neill, RJ
Tronko, MD
Chanock, S
Mabuchi, K
Likhtarov, IA
Kovgan, LM
Drozdovitch, V
Little, MP
Hatch, M
Zablotska, LB
Shpak, VM
McConnell, RJ
Brenner, AV
AF Bogdanova, Tetiana I.
Zurnadzhy, Liudmyla Yu
Nikiforov, Yuri E.
Leeman-Neill, Rebecca J.
Tronko, Mykola D.
Chanock, Stephen
Mabuchi, Kiyohiko
Likhtarov, Ilya A.
Kovgan, Leonila M.
Drozdovitch, Vladimir
Little, Mark P.
Hatch, Maureen
Zablotska, Lydia B.
Shpak, Viktor M.
McConnell, Robert J.
Brenner, Alina V.
TI Histopathological features of papillary thyroid carcinomas detected
during four screening examinations of a Ukrainian-American cohort
SO BRITISH JOURNAL OF CANCER
LA English
DT Article
DE thyroid cancer; papillary thyroid carcinoma; radiation; iodine-131;
pathology; Chernobyl; Chornobyl
ID ATOMIC-BOMB SURVIVORS; CHERNOBYL ACCIDENT; CANCER; RADIATION; CHILDREN;
DISEASES; I-131; REARRANGEMENTS; MUTATION; RET/PTC
AB Background: There are limited data on the histopathology of papillary thyroid carcinomas (PTCs) diagnosed in irradiated populations. We evaluated the associations between iodine-131 dose and the histopathological characteristics of post-Chernobyl PTCs, the changes in these characteristics over time, and their associations with selected somatic mutations.
Methods: This study included 115 PTCs diagnosed in a Ukrainian-American cohort (n = 13 243) during prescreening and four successive thyroid screenings. Of these PTCs, 65 were subjected to somatic mutation profiling. All individuals were <18 years at the time of the Chernobyl accident and had direct thyroid radioactivity measurements. Statistical analyses included multivariate linear and logistic regression.
Results: We identified a borderline significant linear-quadratic association (P = 0.063) between iodine-131 dose and overall tumour invasiveness (presence of extrathyroidal extension, lymphatic/vascular invasion, and regional or distant metastases). Irrespective of dose, tumours with chromosomal rearrangements were more likely to have lymphatic/vascular invasion than tumours without chromosomal rearrangements (P = 0.020) or tumours with BRAF or RAS point mutations (P = 0.008). Controlling for age, there were significant time trends in decreasing tumour size (Po0.001), the extent of lymphatic/vascular invasion (P = 0.005), and overall invasiveness (P = 0.026).
Conclusions: We determined that the invasive properties of PTCs that develop in iodine-131-exposed children may be associated with radiation dose. In addition, based on a subset of cases, tumours with chromosomal rearrangements appear to have a more invasive phenotype. The increase in small, less invasive PTCs over time is a consequence of repeated screening examinations.
C1 [Bogdanova, Tetiana I.; Zurnadzhy, Liudmyla Yu] Ukraine Acad Med Sci, Lab Morphol Endocrine Syst, State Inst VP Komisarenko Inst Endocrinol & Metab, UA-254114 Kiev, Ukraine.
[Nikiforov, Yuri E.; Leeman-Neill, Rebecca J.] Univ Pittsburgh, Sch Med, Dept Pathol, Pittsburgh, PA 15213 USA.
[Tronko, Mykola D.] Ukraine Acad Med Sci, State Inst VP Komisarenko Inst Endocrinol & Metab, Dept Fundamental & Appl Problems Endocrinol, UA-254114 Kiev, Ukraine.
[Chanock, Stephen; Mabuchi, Kiyohiko; Drozdovitch, Vladimir; Little, Mark P.; Hatch, Maureen; Brenner, Alina V.] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Likhtarov, Ilya A.] Ukraine Acad Med Sci, State Inst Natl Res Ctr Radiat Med, Dept Dosimetry & Radiat Protect, UA-04050 Kiev, Ukraine.
[Kovgan, Leonila M.] Ukraine Acad Med Sci, State Inst Natl Res Ctr Radiat Med, Lab Radiat Protect, UA-04050 Kiev, Ukraine.
[Zablotska, Lydia B.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94118 USA.
[Shpak, Viktor M.] Ukraine Acad Med Sci, State Inst VP Komisarenko Inst Endocrinol & Metab, Dept Med Consequences Chernobyl Accid & Int Coope, UA-254114 Kiev, Ukraine.
[McConnell, Robert J.] Columbia Univ, Thyroid Ctr, New York, NY 10032 USA.
[McConnell, Robert J.] Columbia Univ, Coll Phys & Surg, Dept Med, New York, NY USA.
RP Brenner, AV (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, 9609 Med Ctr Dr,MSC 9778, Bethesda, MD 20892 USA.
EM brennera@mail.nih.gov
OI Little, Mark/0000-0003-0980-7567
FU NIH [R01 CA88041, NO1-CP-21178, CA132918]; Intramural Research Program
of the National Institutes of Health, National Cancer Institute;
Department of Energy; US Nuclear Regulatory Commission
FX We acknowledge the commitment of our Colleagues at the Institute of
Endocrinology and Metabolism (IEM) in Ukraine who performed all four
screening examinations, particularly the staff of the Laboratory of
Endocrine System Morphology who collected histopathological samples from
the Ukrainian-American cohort and staff of the Surgery Department who
operated on these patients. We also acknowledge our American colleagues,
Drs. J Robbins, E Greenebaum, and P O'Kane, who collaborated with us
over many years and participated in discussions of clinical and
histopathological data. We gratefully acknowledge the confirmation of
diagnoses provided by the International Pathology Panel of the Chernobyl
Tissue Bank: Professors A Abrosimov, T Bogdanova, G Fadda, J Hunt, M
Ito, V Livolsi, J Rosai, and ED Williams. This research was supported by
the Intramural Research Program of the National Institutes of Health,
National Cancer Institute, and the Department of Energy. The US Nuclear
Regulatory Commission provided the initial funds for equipment purchase.
The work of Drs. Nikiforov and Leeman-Neill was in part supported by NIH
grant R01 CA88041 to YEN; Drs. Zablotska and McConnell by contract
NO1-CP-21178 to LBZ and RJM and grant CA132918 to LBZ
NR 41
TC 2
Z9 5
U1 2
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 DEC 1
PY 2015
VL 113
IS 11
BP 1556
EP 1564
DI 10.1038/bjc.2015.372
PG 9
WC Oncology
SC Oncology
GA CZ5UL
UT WOS:000367167400005
PM 26625214
ER
PT J
AU Alexander, SPH
Kelly, E
Marrion, N
Peters, JA
Benson, HE
Faccenda, E
Pawson, AJ
Sharman, JL
Southan, C
Buneman, OP
Catterall, WA
Cidlowski, JA
Davenport, AP
Fabbro, D
Fan, G
McGrath, JC
Spedding, M
Davies, JA
Aldrich, R
Attali, B
Back, M
Barnes, NM
Bathgate, R
Beart, PM
Becirovic, E
Biel, M
Birdsall, NJ
Boison, D
Brauner-Osborne, H
Broer, S
Bryant, C
Burnstock, G
Burris, T
Cain, D
Calo, G
Chan, SL
Chandy, KG
Chiang, N
Christakos, S
Christopoulos, A
Chun, JJ
Chung, JJ
Clapham, DE
Connor, MA
Coons, L
Cox, HM
Dautzenberg, FM
Dent, G
Douglas, SD
Dubocovich, ML
Edwards, DP
Farndale, R
Fong, TM
Forrest, D
Fowler, CJ
Fuller, P
Gainetdinov, RR
Gershengorn, MA
Goldin, A
Goldstein, SAN
Grimm, SL
Grissmer, S
Gundlach, AL
Hagenbuch, B
Hammond, JR
Hancox, JC
Hartig, S
Hauger, RL
Hay, DL
Hebert, T
Hollenberg, AN
Holliday, ND
Hoyer, D
Ijzerman, AP
Inui, KI
Ishii, S
Jacobson, KA
Jan, LY
Jarvis, GE
Jensen, R
Jetten, A
Jockers, R
Kaczmarek, LK
Kanai, Y
Kang, HS
Karnik, S
Kerr, ID
Korach, KS
Lange, CA
Larhammar, D
Leeb-Lundberg, F
Leurs, R
Lolait, SJ
Macewan, D
Maguire, JJ
May, JM
Mazella, J
McArdle, CA
McDonnell, DP
Michel, MC
Miller, LJ
Mitolo, V
Monie, T
Monk, PN
Mouillac, B
Murphy, PM
Nahon, JL
Nerbonne, J
Nichols, CG
Norel, X
Oakley, R
Offermanns, S
Palmer, LG
Panaro, MA
Perez-Reyes, E
Pertwee, RG
Pike, JW
Pin, JP
Pintor, S
Plant, LD
Poyner, DR
Prossnitz, ER
Pyne, S
Ren, D
Richer, JK
Rondard, P
Ross, RA
Sackin, H
Safi, R
Sanguinetti, MC
Sartorius, CA
Segaloff, DL
Sladek, FM
Stewart, G
Stoddart, LA
Striessnig, J
Summers, RJ
Takeda, Y
Tetel, M
Toll, L
Trimmer, JS
Tsai, MJ
Tsai, SY
Tucker, S
Usdin, TB
Vilargada, JP
Vore, M
Ward, DT
Waxman, SG
Webb, P
Wei, AD
Weigel, N
Willars, GB
Winrow, C
Wong, SS
Wulff, H
Ye, RD
Young, M
Zajac, JM
AF Alexander, Stephen P. H.
Kelly, Eamonn
Marrion, Neil
Peters, John A.
Benson, Helen E.
Faccenda, Elena
Pawson, Adam J.
Sharman, Joanna L.
Southan, Christopher
Buneman, O. Peter
Catterall, William A.
Cidlowski, John A.
Davenport, Anthony P.
Fabbro, Doriano
Fan, Grace
McGrath, John C.
Spedding, Michael
Davies, Jamie A.
Aldrich, R.
Attali, B.
Back, M.
Barnes, N. M.
Bathgate, R.
Beart, P. M.
Becirovic, E.
Biel, M.
Birdsall, N. J.
Boison, D.
Brauner-Osborne, H.
Broeer, S.
Bryant, C.
Burnstock, G.
Burris, T.
Cain, D.
Calo, G.
Chan, S. L.
Chandy, K. G.
Chiang, N.
Christakos, S.
Christopoulos, A.
Chun, J. J.
Chung, J. -J.
Clapham, D. E.
Connor, M. A.
Coons, L.
Cox, H. M.
Dautzenberg, F. M.
Dent, G.
Douglas, S. D.
Dubocovich, M. L.
Edwards, D. P.
Farndale, R.
Fong, T. M.
Forrest, D.
Fowler, C. J.
Fuller, P.
Gainetdinov, R. R.
Gershengorn, M. A.
Goldin, A.
Goldstein, S. A. N.
Grimm, S. L.
Grissmer, S.
Gundlach, A. L.
Hagenbuch, B.
Hammond, J. R.
Hancox, J. C.
Hartig, S.
Hauger, R. L.
Hay, D. L.
Hebert, T.
Hollenberg, A. N.
Holliday, N. D.
Hoyer, D.
Ijzerman, A. P.
Inui, K. I.
Ishii, S.
Jacobson, K. A.
Jan, L. Y.
Jarvis, G. E.
Jensen, R.
Jetten, A.
Jockers, R.
Kaczmarek, L. K.
Kanai, Y.
Kang, H. S.
Karnik, S.
Kerr, I. D.
Korach, K. S.
Lange, C. A.
Larhammar, D.
Leeb-Lundberg, F.
Leurs, R.
Lolait, S. J.
Macewan, D.
Maguire, J. J.
May, J. M.
Mazella, J.
McArdle, C. A.
McDonnell, D. P.
Michel, M. C.
Miller, L. J.
Mitolo, V.
Monie, T.
Monk, P. N.
Mouillac, B.
Murphy, P. M.
Nahon, J. -L.
Nerbonne, J.
Nichols, C. G.
Norel, X.
Oakley, R.
Offermanns, S.
Palmer, L. G.
Panaro, M. A.
Perez-Reyes, E.
Pertwee, R. G.
Pike, J. W.
Pin, J. P.
Pintor, S.
Plant, L. D.
Poyner, D. R.
Prossnitz, E. R.
Pyne, S.
Ren, D.
Richer, J. K.
Rondard, P.
Ross, R. A.
Sackin, H.
Safi, R.
Sanguinetti, M. C.
Sartorius, C. A.
Segaloff, D. L.
Sladek, F. M.
Stewart, G.
Stoddart, L. A.
Striessnig, J.
Summers, R. J.
Takeda, Y.
Tetel, M.
Toll, L.
Trimmer, J. S.
Tsai, M. -J.
Tsai, S. Y.
Tucker, S.
Usdin, T. B.
Vilargada, J. -P.
Vore, M.
Ward, D. T.
Waxman, S. G.
Webb, P.
Wei, A. D.
Weigel, N.
Willars, G. B.
Winrow, C.
Wong, S. S.
Wulff, H.
Ye, R. D.
Young, M.
Zajac, J. -M.
CA CGTP Collaborators
TI THE CONCISE GUIDE TO PHARMACOLOGY 2015/16: Overview
SO BRITISH JOURNAL OF PHARMACOLOGY
LA English
DT Article
AB The Concise Guide to PHARMACOLOGY 2015/16 provides concise overviews of the key properties of over 1750 human drug targets with their pharmacology, plus links to an open access knowledgebase of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. The full contents can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.13347/full. This compilation of the major pharmacological targets is divided into eight areas of focus: G protein-coupled receptors, ligand-gated ion channels, voltage-gated ion channels, other ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The Concise Guide is published in landscape format in order to facilitate comparison of related targets. It is a condensed version of material contemporary to late 2015, which is presented in greater detail and constantly updated on the website www.guidetopharmacology.org, superseding data presented in the previous Guides to Receptors & Channels and the Concise Guide to PHARMACOLOGY 2013/14. It is produced in conjunction with NC-IUPHAR and provides the official IUPHAR classification and nomenclature for human drug targets, where appropriate. It consolidates information previously curated and displayed separately in IUPHAR-DB and GRAC and provides a permanent, citable, point-in-time record that will survive database updates.
C1 [Alexander, Stephen P. H.] Univ Nottingham, Sch Med, Sch Biomed Sci, Nottingham NG7 2UH, England.
[Kelly, Eamonn; Marrion, Neil] Univ Bristol, Sch Physiol & Pharmacol, Bristol BS8 1TD, Avon, England.
[Peters, John A.] Univ Dundee, Med Educ Inst, Ninewells Hosp & Med Sch, Neurosci Div, Dundee DD1 9SY, Scotland.
[Benson, Helen E.; Faccenda, Elena; Pawson, Adam J.; Sharman, Joanna L.; Southan, Christopher; Davies, Jamie A.] Univ Edinburgh, Ctr Integrat Physiol, Edinburgh EH8 9XD, Midlothian, Scotland.
[Buneman, O. Peter] Univ Edinburgh, Sch Informat, Lab Foundat Comp Sci, Edinburgh EH8 9LE, Midlothian, Scotland.
[Catterall, William A.] Univ Washington, Dept Pharmacol, Seattle, WA 98195 USA.
[Cidlowski, John A.] NIEHS, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
[Davenport, Anthony P.] Univ Cambridge, Clin Pharmacol Unit, Cambridge CB2 0QQ, England.
[Fabbro, Doriano] PIQUR Therapeut, CH-4057 Basel, Switzerland.
[Fan, Grace] Agnes Irwin Sch, Rosemont, PA USA.
[McGrath, John C.] Univ Glasgow, Sch Life Sci, Glasgow G12 8QQ, Lanark, Scotland.
[Spedding, Michael] Spedding Res Solut SARL, F-78110 Le Vesinet, France.
RP Alexander, SPH (reprint author), Univ Nottingham, Sch Med, Sch Biomed Sci, Nottingham NG7 2UH, England.
RI Alexander, Steve/B-8105-2009; Brauner-Osborne, Hans/D-7260-2011; Zajac,
jean-marie/E-5129-2010; Winrow, Christopher/K-1864-2014; Connor,
Mark/A-4197-2008; Monk, Peter/C-6155-2008; Ye, Richard/O-5223-2016;
Mazella, Jean/A-6767-2012; NAHON, Jean-Louis/O-7977-2016; Gainetdinov,
Raul/G-5875-2011; Jacobson, Kenneth/A-1530-2009; Pawson,
Adam/Q-5678-2016
OI Sharman, Joanna/0000-0002-5275-6446; Norel, Xavier/0000-0003-0734-3359;
McArdle, Craig/0000-0003-4836-5351; Gainetdinov,
Raul/0000-0003-2951-6038; Alexander, Steve/0000-0003-4417-497X;
Brauner-Osborne, Hans/0000-0001-9495-7388; Connor,
Mark/0000-0003-2538-2001; Monk, Peter/0000-0003-4637-3059; Ye,
Richard/0000-0002-2164-5620; Mazella, Jean/0000-0002-5627-0742; NAHON,
Jean-Louis/0000-0001-9572-7779; Jacobson, Kenneth/0000-0001-8104-1493;
Pawson, Adam/0000-0003-2280-845X
FU British Pharmacological Society; International Union of Basic and
Clinical Pharmacology; Wellcome Trust [099156/Z/12/Z]; University of
Edinburgh
FX We are extremely grateful for the financial contributions from the
British Pharmacological Society, the International Union of Basic and
Clinical Pharmacology, the Wellcome Trust (099156/Z/12/Z]), which
support the website and the University of Edinburgh, who host the
guidetopharmacology.org website. We are also tremendously grateful to
the long list of collaborators from NC-IUPHAR subcommittees and beyond,
who have assisted in the construction of the Concise Guide to
PHARMACOLOGY 2015/16 and the online database
www.GuideToPHARMACOLOGY.org.
NR 10
TC 49
Z9 49
U1 3
U2 12
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0007-1188
EI 1476-5381
J9 BRIT J PHARMACOL
JI Br. J. Pharmacol.
PD DEC
PY 2015
VL 172
IS 24
SI SI
BP 5729
EP 5743
DI 10.1111/bph.13347
PG 15
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA CY6HT
UT WOS:000366510500001
PM 26650438
ER
PT J
AU Alexander, SPH
Cidlowski, JA
Kelly, E
Marrion, N
Peters, JA
Benson, HE
Faccenda, E
Pawson, AJ
Sharman, JL
Southan, C
Davies, JA
Aldrich, R
Attali, B
Back, M
Barnes, NM
Bathgate, R
Beart, PM
Becirovic, E
Biel, M
Birdsall, NJ
Boison, D
Brauner-Osborne, H
Broer, S
Bryant, C
Burnstock, G
Burris, T
Cain, D
Calo, G
Chan, SL
Chandy, KG
Chiang, N
Christakos, S
Christopoulos, A
Chun, JJ
Chung, JJ
Clapham, DE
Connor, MA
Coons, L
Cox, HM
Dautzenberg, FM
Dent, G
Douglas, SD
Dubocovich, ML
Edwards, DP
Farndale, R
Fong, TM
Forrest, D
Fowler, CJ
Fuller, P
Gainetdinov, RR
Gershengorn, MA
Goldin, A
Goldstein, SAN
Grimm, SL
Grissmer, S
Gundlach, AL
Hagenbuch, B
Hammond, JR
Hancox, JC
Hartig, S
Hauger, RL
Hay, DL
Hebert, T
Hollenberg, AN
Holliday, ND
Hoyer, D
Ijzerman, AP
Inui, KI
Ishii, S
Jacobson, KA
Jan, LY
Jarvis, GE
Jensen, R
Jetten, A
Jockers, R
Kaczmarek, LK
Kanai, Y
Kang, HS
Karnik, S
Kerr, ID
Korach, KS
Lange, CA
Larhammar, D
Leeb-Lundberg, F
Leurs, R
Lolait, SJ
Macewan, D
Maguire, JJ
May, JM
Mazella, J
McArdle, CA
McDonnell, DP
Michel, MC
Miller, LJ
Mitolo, V
Monie, T
Monk, PN
Mouillac, B
Murphy, PM
Nahon, JL
Nerbonne, J
Nichols, CG
Norel, X
Oakley, R
Offermanns, S
Palmer, LG
Panaro, MA
Perez-Reyes, E
Pertwee, RG
Pike, JW
Pin, JP
Pintor, S
Plant, LD
Poyner, DR
Prossnitz, ER
Pyne, S
Ren, D
Richer, JK
Rondard, P
Ross, RA
Sackin, H
Safi, R
Sanguinetti, MC
Sartorius, CA
Segaloff, DL
Sladek, FM
Stewart, G
Stoddart, LA
Striessnig, J
Summers, RJ
Takeda, Y
Tetel, M
Toll, L
Trimmer, JS
Tsai, MJ
Tsai, SY
Tucker, S
Usdin, TB
J-P, V
Vore, M
Ward, DT
Waxman, SG
Webb, P
Wei, AD
Weigel, N
Willars, GB
Winrow, C
Wong, SS
Wulff, H
Ye, RD
Young, M
Zajac, JM
AF Alexander, Stephen P. H.
Cidlowski, John A.
Kelly, Eamonn
Marrion, Neil
Peters, John A.
Benson, Helen E.
Faccenda, Elena
Pawson, Adam J.
Sharman, Joanna L.
Southan, Christopher
Davies, Jamie A.
Aldrich, R.
Attali, B.
Back, M.
Barnes, N. M.
Bathgate, R.
Beart, P. M.
Becirovic, E.
Biel, M.
Birdsall, N. J.
Boison, D.
Brauner-Osborne, H.
Broeer, S.
Bryant, C.
Burnstock, G.
Burris, T.
Cain, D.
Calo, G.
Chan, S. L.
Chandy, K. G.
Chiang, N.
Christakos, S.
Christopoulos, A.
Chun, J. J.
Chung, J. -J.
Clapham, D. E.
Connor, M. A.
Coons, L.
Cox, H. M.
Dautzenberg, F. M.
Dent, G.
Douglas, S. D.
Dubocovich, M. L.
Edwards, D. P.
Farndale, R.
Fong, T. M.
Forrest, D.
Fowler, C. J.
Fuller, P.
Gainetdinov, R. R.
Gershengorn, M. A.
Goldin, A.
Goldstein, S. A. N.
Grimm, S. L.
Grissmer, S.
Gundlach, A. L.
Hagenbuch, B.
Hammond, J. R.
Hancox, J. C.
Hartig, S.
Hauger, R. L.
Hay, D. L.
Hebert, T.
Hollenberg, A. N.
Holliday, N. D.
Hoyer, D.
Ijzerman, A. P.
Inui, K. I.
Ishii, S.
Jacobson, K. A.
Jan, L. Y.
Jarvis, G. E.
Jensen, R.
Jetten, A.
Jockers, R.
Kaczmarek, L. K.
Kanai, Y.
Kang, H. S.
Karnik, S.
Kerr, I. D.
Korach, K. S.
Lange, C. A.
Larhammar, D.
Leeb-Lundberg, F.
Leurs, R.
Lolait, S. J.
Macewan, D.
Maguire, J. J.
May, J. M.
Mazella, J.
McArdle, C. A.
McDonnell, D. P.
Michel, M. C.
Miller, L. J.
Mitolo, V.
Monie, T.
Monk, P. N.
Mouillac, B.
Murphy, P. M.
Nahon, J. -L.
Nerbonne, J.
Nichols, C. G.
Norel, X.
Oakley, R.
Offermanns, S.
Palmer, L. G.
Panaro, M. A.
Perez-Reyes, E.
Pertwee, R. G.
Pike, J. W.
Pin, J. P.
Pintor, S.
Plant, L. D.
Poyner, D. R.
Prossnitz, E. R.
Pyne, S.
Ren, D.
Richer, J. K.
Rondard, P.
Ross, R. A.
Sackin, H.
Safi, R.
Sanguinetti, M. C.
Sartorius, C. A.
Segaloff, D. L.
Sladek, F. M.
Stewart, G.
Stoddart, L. A.
Striessnig, J.
Summers, R. J.
Takeda, Y.
Tetel, M.
Toll, L.
Trimmer, J. S.
Tsai, M. -J.
Tsai, S. Y.
Tucker, S.
Usdin, T. B.
Vilargada, J. -P.
Vore, M.
Ward, D. T.
Waxman, S. G.
Webb, P.
Wei, A. D.
Weigel, N.
Willars, G. B.
Winrow, C.
Wong, S. S.
Wulff, H.
Ye, R. D.
Young, M.
Zajac, J. -M.
CA CGTP Collaborators
TI THE CONCISE GUIDE TO PHARMACOLOGY 2015/16: Nuclear hormone receptors
SO BRITISH JOURNAL OF PHARMACOLOGY
LA English
DT Article
AB The Concise Guide to PHARMACOLOGY 2015/16 provides concise overviews of the key properties of over 1750 human drug targets with their pharmacology, plus links to an open access knowledgebase of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. The full contents can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.13352/full. Nuclear hormone receptors are one of the eight major pharmacological targets into which the Guide is divided, with the others being: G protein-coupled receptors, ligand-gated ion channels, voltage-gated ion channels, other ion channels, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The Concise Guide is published in landscape format in order to facilitate comparison of related targets. It is a condensed version of material contemporary to late 2015, which is presented in greater detail and constantly updated on the website www.guidetopharmacology.org, superseding data presented in the previous Guides to Receptors & Channels and the Concise Guide to PHARMACOLOGY 2013/14. It is produced in conjunction with NC-IUPHAR and provides the official IUPHAR classification and nomenclature for human drug targets, where appropriate. It consolidates information previously curated and displayed separately in IUPHAR-DB and GRAC and provides a permanent, citable, point-in-time record that will survive database updates.
C1 [Alexander, Stephen P. H.] Univ Nottingham, Sch Med, Sch Biomed Sci, Nottingham NG7 2UH, England.
[Cidlowski, John A.] NIEHS, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
[Kelly, Eamonn; Marrion, Neil] Univ Bristol, Sch Physiol & Pharmacol, Bristol BS8 1TD, Avon, England.
[Peters, John A.] Univ Dundee, Med Educ Inst, Ninewells Hosp & Med Sch, Neurosci Div, Dundee DD1 9SY, Scotland.
[Benson, Helen E.; Faccenda, Elena; Pawson, Adam J.; Sharman, Joanna L.; Southan, Christopher; Davies, Jamie A.] Univ Edinburgh, Ctr Integrat Physiol, Edinburgh EH8 9XD, Midlothian, Scotland.
RP Alexander, SPH (reprint author), Univ Nottingham, Sch Med, Sch Biomed Sci, Nottingham NG7 2UH, England.
RI Alexander, Steve/B-8105-2009; Connor, Mark/A-4197-2008; Ye,
Richard/O-5223-2016; Mazella, Jean/A-6767-2012; Gainetdinov,
Raul/G-5875-2011; Jacobson, Kenneth/A-1530-2009; Pawson,
Adam/Q-5678-2016; Safi, Rachid/A-5909-2010;
OI Alexander, Steve/0000-0003-4417-497X; Connor, Mark/0000-0003-2538-2001;
Ye, Richard/0000-0002-2164-5620; Mazella, Jean/0000-0002-5627-0742;
Jacobson, Kenneth/0000-0001-8104-1493; Pawson, Adam/0000-0003-2280-845X;
Sharman, Joanna/0000-0002-5275-6446; Southan,
Christopher/0000-0001-9580-0446
NR 0
TC 26
Z9 26
U1 0
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0007-1188
EI 1476-5381
J9 BRIT J PHARMACOL
JI Br. J. Pharmacol.
PD DEC
PY 2015
VL 172
IS 24
SI SI
BP 5956
EP 5978
DI 10.1111/bph.13352
PG 23
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA CY6HT
UT WOS:000366510500006
PM 26650443
ER
PT J
AU Klar, AJS
AF Klar, Amar J. S.
TI Selective chromatid segregation mechanism proposed for the human split
hand/foot malformation development by chromosome 2 translocations: A
perspective
SO DEVELOPMENTAL BIOLOGY
LA English
DT Article
DE Limb development; Split hand/split foot malformation; Monochromatid gene
expression; Selective strand/chromatid segregation mechanism; Asymmetric
cell division mechanism; Epigenetic developmental mechanism
ID LEFT-RIGHT ASYMMETRY; FISSION YEAST; DNA STRANDS; FOOT MALFORMATION;
EPIGENETIC STATES; CELL-DIVISION; INHERITANCE; LOCUS; MODEL;
SCHIZOPHRENIA
AB Three unrelated chromosome 2q14.1-14.2 region translocations caused the split hand/foot limb malformation development in humans by an unknown mechanism. Their etiology was described by the autosomal dominant inheritance with incomplete penetrance genetic model although authors stated, "the understanding of the genotype-to-phenotype relationship has been most challenging". The conundrums are that no mutation was found in known genes located at or near the translocation breakpoints, some limbs were malformed while others were not in the same patient and surprisingly breakpoints lie at relatively large distance of more than 2.5 million bases to have caused disorder-causing gene mutations in a single gene. To help understand translocations etiology for limb development, we invoke the selective DNA strand/chromatid-specific epigenetic imprinting and segregation mechanism employed by the two highly diverged fission yeasts to produce daughter cells of different cell types by mitosis. By this mechanism, an anterior- and posterior-limb-tissues-generating pair of daughter cells is produced by a single deterministic cell dividing in the anlagen of the limb bud. Accordingly, malformation develops simply because translocations hinder the proper distribution of chromatid-specific epialleles of a limb developmental gene during the deterministic cell's mitosis. It is tempting to speculate that such a mechanism might involve the HOXD-cluster genes situated centromere-distal to the translocation breakpoints many million bases away at the 2q31.1 region. Further genetic tests of the hypothesis are proposed for the human and mouse limb development. In sum, genetic analysis of translocations suggests that the sequence asymmetry of strands in the double-helical DNA structure of a developmental gene forms the physical basis of daughter cells' developmental asymmetry, thus opposing the morphogen-gradient research paradigm of limb development. Published by Elsevier Inc.
C1 [Klar, Amar J. S.] NCI, Gene Regulat & Chromosome Biol Lab, Ctr Canc Res, NIH, Frederick, MD 21702 USA.
RP Klar, AJS (reprint author), NCI, Gene Regulat & Chromosome Biol Lab, Ctr Canc Res, NIH, Bldg 539,Room 154, Frederick, MD 21702 USA.
EM klara@mail.nih.gov
FU Intramural Research Program of the National Cancer Institute, National
Institutes of Health
FX The Intramural Research Program of the National Cancer Institute,
National Institutes of Health, supports this research.
NR 46
TC 3
Z9 3
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 0012-1606
EI 1095-564X
J9 DEV BIOL
JI Dev. Biol.
PD DEC 1
PY 2015
VL 408
IS 1
BP 7
EP 13
DI 10.1016/j.ydbio.2015.10.013
PG 7
WC Developmental Biology
SC Developmental Biology
GA CZ2TE
UT WOS:000366956700004
PM 26477560
ER
PT J
AU Ajima, R
Bisson, JA
Helt, JC
Nakaya, MA
Habas, R
Tessarollo, L
He, X
Morrisey, EE
Yamaguchi, TP
Cohen, ED
AF Ajima, Rieko
Bisson, Joseph A.
Helt, Jay-Christian
Nakaya, Masa-Aki
Habas, Raymond
Tessarollo, Lino
He, Xi
Morrisey, Edward E.
Yamaguchi, Terry P.
Cohen, Ethan David
TI DAAM1 and DAAM2 are co-required for myocardial maturation and sarcomere
assembly
SO DEVELOPMENTAL BIOLOGY
LA English
DT Article
ID PLANAR CELL POLARITY; 2ND HEART FIELD; LEFT-VENTRICULAR NONCOMPACTION;
NON-COMPACTION CARDIOMYOPATHY; CARDIAC PROGENITOR CELLS; TYROSINE KINASE
ROR2; RICTOR-MTOR COMPLEX; SIGNALING PATHWAY; OUTFLOW TRACT; MAMMALIAN
CARDIOMYOCYTES
AB Wnt ligands regulate heart morphogenesis but the underlying mechanisms remain unclear. Two Formin-related proteins, DAAM1 and 2, were previously found to bind the Wnt effector Disheveled. Here, since DAAM1 and 2 nucleate actin and mediate Wnt-induced cytoskeletal changes, a foxed-allele of Daam1 was used to disrupt its function specifically in the myocardium and investigate Wnt-associated pathways. Homozygous Daam1 conditional knockout (CKO) mice were viable but had misshapen hearts and poor cardiac function. The defects in Daam1 CKO mice were observed by mid-gestation and were associated with a loss of protrusions from cardiomyocytes invading the outflow tract. Further, these mice exhibited noncompaction cardiomyopathy (NCM) and deranged cardiomyocyte polarity. Interestingly, Daam1 CKO mice that were also homozygous for an insertion disrupting Daam2 (DKO) had stronger NCM, severely reduced cardiac function, disrupted sarcomere structure, and increased myocardial proliferation, suggesting that DAAM1 and DAAM2 have redundant functions. While RhoA was unaffected in the hearts of Daam1/2 DM mice, AKT activity was lower than in controls, raising the issue of whether DAAM1/2 are only mediating Wnt signaling. Daam/-floxed mice were thus bred to Wnt5a null mice to identify genetic interactions. The hearts of Daam1 CKO mice that were also heterozygous for the null allele of Wnt5a had stronger NCM and more severe loss of cardiac function than Daam1 CKO mice, consistent with DAAM1 and Wnt5a acting in a common pathway. However, deleting Daam1 further disrupted Wnt5a homozygous-null hearts, suggesting that DAAM1 also has Wnt5a-independent roles in cardiac development. Published by Elsevier Inc.
C1 [Ajima, Rieko] Natl Inst Genet, Mammalian Dev Lab, Mishima, Shizuoka 4118540, Japan.
[Bisson, Joseph A.; Helt, Jay-Christian; Cohen, Ethan David] Univ Rochester, Sch Med & Dent, Dept Med, Rochester, NY 14642 USA.
[Nakaya, Masa-Aki; Yamaguchi, Terry P.] NCI, Canc & Dev Biol Lab, Ctr Canc Res, NIH, Frederick, MD 21702 USA.
[Habas, Raymond] Temple Univ, Coll Sci & Technol, Dept Biol, Philadelphia, PA 19122 USA.
[Tessarollo, Lino] NCI, Neural Dev Sect, Mouse Canc Genet Program, Ctr Canc Res, Frederick, MD 21702 USA.
[He, Xi] Harvard Univ, Boston Childrens Hosp, Sch Med, FM Kirby Neurobiol Ctr,Dept Neurol, Boston, MA 02115 USA.
[Morrisey, Edward E.] Univ Penn, Dept Med & Cell & Dev Biol, Philadelphia, PA 19104 USA.
RP Yamaguchi, TP (reprint author), NCI, Canc & Dev Biol Lab, NIH, POB B 1050,Boyles St Bldg 539,Rm 218, Frederick, MD 21702 USA.
EM yamagute@mail.nih.gov; ethan_cohen@urmc.rochester.edu
FU Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research; Progenitor Cell Biology Consortium Grant
[HL100405]; American Heart Association [10SDG2610019, 15GRNT23020024]
FX This research was supported by the Intramural Research Program of the
NIH, National Cancer Institute, Center for Cancer Research, as well as
the Progenitor Cell Biology Consortium Grant (HL100405) and American
Heart Association (10SDG2610019 and 15GRNT23020024).
NR 85
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 0012-1606
EI 1095-564X
J9 DEV BIOL
JI Dev. Biol.
PD DEC 1
PY 2015
VL 408
IS 1
BP 126
EP 139
DI 10.1016/j.ydbio.2015.10.003
PG 14
WC Developmental Biology
SC Developmental Biology
GA CZ2TE
UT WOS:000366956700014
PM 26526197
ER
PT J
AU Soeiro-de-Souza, MG
Henning, A
Machado-Vieira, R
Moreno, RA
Pastorello, BF
Leite, CD
Vallada, H
Otaduy, MCG
AF Soeiro-de-Souza, Marcio Gerhardt
Henning, Anke
Machado-Vieira, Rodrigo
Moreno, Ricardo A.
Pastorello, Bruno F.
Leite, Claudia da Costa
Vallada, Homero
Garcia Otaduy, Maria Concepcion
TI Anterior cingulate Glutamate-Glutamine cycle metabolites are altered in
euthymic bipolar I disorder
SO EUROPEAN NEUROPSYCHOPHARMACOLOGY
LA English
DT Article
DE GABA; Glutamine; Glutamate; Bipolar; Spectroscopy
ID MAGNETIC-RESONANCE-SPECTROSCOPY; AMINOBUTYRIC-ACID CONCENTRATIONS; MOOD
DISORDERS; BRAIN-METABOLITES; PRIOR-KNOWLEDGE; RATING-SCALE; PROTON MRS;
GABA; SCHIZOPHRENIA; NMR
AB Bipolar disorder (BD) has been consistently associated with abnormalities in the Glutamate/GABA-Glutamine cycle. Magnetic resonance spectroscopy (MRS) studies have reported increased brain Glutamate (Glu) and Glx (Glu+Glutamine) in subjects with BD. However, data on separate measures of GABA and Glutamine (Gln) in BD are sparse due to overlapping resonant signals. The development of new sequence methods in the quantification of these metabolites has allowed a better understanding of the Glu/GABA-Gln cycle but data on this field of research remains sparse in BD. Eighty-eight subjects (50 euthymic BD and 38 HC) underwent 3T proton magnetic resonance spectroscopy (1H MRS) in the anterior cingulate cortex (ACC; 2 x 2 x4.5 cm(3)) using a two-dimensional JPRESS sequence. GABA, Glutamine (Gln) and Glutamate (Glu) were quantified with the Pro Fit program. Using image segmentation and known creatine (Cre) concentrations for white and grey matter, metabolite concentrations were calculated for the excited MRS voxel. GABA levels did not differ between groups. Gin level was higher in euthymic BD patients than in healthy controls. The Glu level and Glu/Gln ratio were lower in BD patients than in controls. The use of anticonvulsants was associated with Gln increase but did not affect Glu or Glu/Gln. Neither lithium nor antipsychotic use influenced metabolite levels. The ACC MRS findings indicate that the glutamatergic function in euthymic medicated BD patients is altered relative to controls. Whether this feature is a metabolic signature of euthymic BD subjects should be the focus of future studies. (C) 2015 Elsevier B.V. and ECNR All rights reserved.
C1 [Soeiro-de-Souza, Marcio Gerhardt; Moreno, Ricardo A.] Univ Sao Paulo IPq FMUSP, Sch Med, Inst Psychiat, Mood Disorders Unit GRUDA, Sao Paulo, Brazil.
[Machado-Vieira, Rodrigo] NIMH, NIH, Bethesda, MD 20892 USA.
[Pastorello, Bruno F.; Leite, Claudia da Costa; Garcia Otaduy, Maria Concepcion] Univ Sao Paulo InRad FMUSP, Dept & Inst Radiol, Lab Magnet Resonance LIM44, Sao Paulo, Brazil.
[Soeiro-de-Souza, Marcio Gerhardt; Vallada, Homero] Univ Sao Paulo InRad FMUSP, Sch Med, Inst Psychiat, Genet & Pharmacogenet Unit PROGENE, Sao Paulo, Brazil.
[Henning, Anke] Inst Biomed Engn Univ, Zurich, Switzerland.
[Henning, Anke] Swiss Fed Inst Technol, Zurich, Switzerland.
[Henning, Anke] Max Planck Inst Biol Cybernet, D-72076 Tubingen, Germany.
RP Soeiro-de-Souza, MG (reprint author), Hosp Clin Sao Paulo, Inst Psiquiatria, Dr Ovidio Pires Campos S-N,Third Floor, BR-05403010 Sao Paulo, Brazil.
EM marciogss@gmail.com
RI Soeiro-de-Souza, Marcio/J-9430-2012; Vallada, Homero/D-1333-2014;
MACHADO-VIEIRA, RODRIGO/D-8293-2012;
OI Soeiro-de-Souza, Marcio/0000-0002-9293-3128; Vallada,
Homero/0000-0001-5123-8295; MACHADO-VIEIRA, RODRIGO/0000-0002-4830-1190;
Henning, Anke/0000-0002-2267-4861
NR 64
TC 6
Z9 6
U1 2
U2 11
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0924-977X
EI 1873-7862
J9 EUR NEUROPSYCHOPHARM
JI Eur. Neuropsychopharmacol.
PD DEC
PY 2015
VL 25
IS 12
BP 2221
EP 2229
DI 10.1016/j.euroneuro.2015.09.020
PG 9
WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA CZ2PO
UT WOS:000366947300004
PM 26476706
ER
PT J
AU Machado-Vieira, R
Gattaz, WF
Zanetti, MV
De Sousa, RT
Carvalho, AF
Soeiro-de-Souza, MG
Leite, CC
Otaduy, MC
AF Machado-Vieira, Rodrigo
Gattaz, Wagner F.
Zanetti, Marcus V.
De Sousa, Rafael T.
Carvalho, Andre F.
Soeiro-de-Souza, Marcio G.
Leite, Claudia C.
Otaduy, Maria C.
TI A Longitudinal (6-week) 3T H-1-MRS Study on the Effects of Lithium
Treatment on Anterior Cingulate Cortex Metabolites in Bipolar Depression
SO EUROPEAN NEUROPSYCHOPHARMACOLOGY
LA English
DT Article
DE Bipolar disorder; Depression; Magnetic resonance spectroscopy; Lithium;
Glutamate; Imaging
ID MAGNETIC-RESONANCE-SPECTROSCOPY; N-ACETYL-ASPARTATE; GRAY-MATTER VOLUME;
MOOD DISORDERS; UNIFYING HYPOTHESIS; CORTICAL GLUTAMATE; OXIDATIVE
STRESS; RATING-SCALE; NITRIC-OXIDE; HUMAN BRAIN
AB The anterior cingulate cortex (ACC) is a key area in mood regulation. To date, no Longitudinal study has specifically evaluated lithium's effects on ACC metabolites using H-1-MRS, as well as its association with clinical improvement in bipolar depression. This H-1-MRS (TE=35 ms) study evaluated 24 drug-free BD patients during depressive episodes and after lithium treatment at therapeutic levels. Brain metabolite levels (N-acetyl aspartate (NM), creatine (tCr), choline, myo-inositol, and glutamate levels) were measured in the ACC at baseline (week 0) and after lithium monotherapy (week 6). The present investigation showed that ACC glutamate (Glu/tCr) and glutamate +glutamine (Glx/tCr) significantly increased after six weeks of lithium therapy. Regarding the association with clinical improvement, remitters showed an increase in myoinositol levels (ml/tCr) after lithium treatment compared to non-remitters. The present findings reinforce a role for ACC glutamate-glutamine cycling and myoinositol pathway as key targets for lithium's therapeutic effects in BD. Published by Elsevier B.V.
C1 [Machado-Vieira, Rodrigo; Gattaz, Wagner F.; Zanetti, Marcus V.; De Sousa, Rafael T.] Univ Sao Paulo, Dept & Inst Psychiat, Lab Neurosci, LIM 27, BR-05508 Sao Paulo, Brazil.
[Machado-Vieira, Rodrigo; Gattaz, Wagner F.; Zanetti, Marcus V.; De Sousa, Rafael T.] Univ Sao Paulo, Ctr Interdisciplinary Res Appl Neurosci NAPNA, BR-05508 Sao Paulo, Brazil.
[Machado-Vieira, Rodrigo; De Sousa, Rafael T.] NIMH, Expt Therapeut & Pathophysiol Branch, NIH, Bethesda, MD 20892 USA.
[Carvalho, Andre F.] Univ Fed Ceara, Fac Med, Dept Clin Med, Fortaleza, Ceara, Brazil.
[Carvalho, Andre F.] Univ Fed Ceara, Fac Med, Translat Psychiat Res Grp, Fortaleza, Ceara, Brazil.
[Soeiro-de-Souza, Marcio G.] Univ Sao Paulo, Dept Psychiat, GRUDA, Mood Disorders Program, BR-05508 Sao Paulo, Brazil.
[Leite, Claudia C.; Otaduy, Maria C.] Univ Sao Paulo, Dept & Inst Psychiat, Lab Magnet Resonance Neuroradiol, LIM 44, BR-05508 Sao Paulo, Brazil.
RP Machado-Vieira, R (reprint author), Univ Sao Paulo, Dept & Inst Psychiat, Lab Neurosci LIM27, BR-05508 Sao Paulo, Brazil.
EM machadovieirar@mail.nih.gov
RI Soeiro-de-Souza, Marcio/J-9430-2012; Leite, Claudia/B-6036-2013;
MACHADO-VIEIRA, RODRIGO/D-8293-2012
OI Soeiro-de-Souza, Marcio/0000-0002-9293-3128; MACHADO-VIEIRA,
RODRIGO/0000-0002-4830-1190
NR 49
TC 4
Z9 4
U1 2
U2 13
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0924-977X
EI 1873-7862
J9 EUR NEUROPSYCHOPHARM
JI Eur. Neuropsychopharmacol.
PD DEC
PY 2015
VL 25
IS 12
BP 2311
EP 2317
DI 10.1016/j.euroneuro.2015.08.023
PG 7
WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA CZ2PO
UT WOS:000366947300013
PM 26428274
ER
PT J
AU Begley, DA
Sundberg, JP
Krupke, DM
Neuhauser, SB
Bult, CJ
Eppig, JT
Morse, HC
Ward, JM
AF Begley, Dale A.
Sundberg, John P.
Krupke, Debra M.
Neuhauser, Steven B.
Bult, Carol J.
Eppig, Janan T.
Morse, Herbert C., III
Ward, Jerrold M.
TI Finding mouse models of human lymphomas and leukemia's using the Jackson
laboratory mouse tumor biology database
SO EXPERIMENTAL AND MOLECULAR PATHOLOGY
LA English
DT Article
DE Lymphoma; Leukemia; Mice; Mouse tumor biology database; Digital slides;
Virtual slides
ID BETHESDA PROPOSALS; ANIMAL-MODELS; CANCER; MICE; NEOPLASMS; DISEASE;
CLASSIFICATION; PATHBASE; UTILITY; LESIONS
AB Many mouse models have been created to study hematopoietic cancer types. There are over thirty hematopoietic tumor types and subtypes, both human and mouse, with various origins, characteristics and clinical prognoses. Determining the specific type of hematopoietic lesion produced in a mouse model and identifying mouse models that correspond to the human subtypes of these lesions has been a continuing challenge for the scientific community. The Mouse Tumor Biology Database (MTB; http://tumor.informatics.jax.org) is designed to facilitate use of mouse models of human cancer by providing detailed histopathologic and molecular information on lymphoma subtypes, including expertly annotated, on line, whole slide scans, and providing a repository for storing information on and querying these data for specific lymphoma models. (C) 2015 Elsevier Inc. All rights reserved.
C1 [Begley, Dale A.; Sundberg, John P.; Krupke, Debra M.; Neuhauser, Steven B.; Bult, Carol J.; Eppig, Janan T.] Jackson Lab, Bar Harbor, ME 04609 USA.
[Morse, Herbert C., III] NIAID, Virol & Cellular Immunol Sect, Immunogenet Lab, NIH, Bethesda, MD 20892 USA.
[Ward, Jerrold M.] Global VetPathol, Montgomery Village, MD USA.
RP Begley, DA (reprint author), Jackson Lab, 600 Main St, Bar Harbor, ME 04609 USA.
EM dale.begley@jax.org
OI Krupke, Debra/0000-0002-3165-2891
FU National Institutes of Health [CA089713]; Intramural Research Program of
the NIH, NIAID; Basic Cancer Center Core Grant from the National Cancer
Institute [CA034196]
FX This work was supported by grants from the National Institutes of Health
(CA089713, for the Mouse Tumor Biology Database) and the Intramural
Research Program of the NIH, NIAID. The Jackson Laboratory Shared
Scientific Services were supported in part by a Basic Cancer Center Core
Grant from the National Cancer Institute (CA034196, to The Jackson
Laboratory).
NR 34
TC 1
Z9 1
U1 1
U2 5
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0014-4800
EI 1096-0945
J9 EXP MOL PATHOL
JI Exp. Mol. Pathol.
PD DEC
PY 2015
VL 99
IS 3
BP 533
EP 536
DI 10.1016/j.yexmp.2015.07.004
PG 4
WC Pathology
SC Pathology
GA CZ2SI
UT WOS:000366954500020
PM 26302176
ER
PT J
AU Neuman, MG
Malnick, S
Maor, Y
Nanau, RM
Melzer, E
Ferenci, P
Seitz, HK
Mueller, S
Mell, H
Samuel, D
Cohen, LB
Kharbanda, KK
Osna, NA
Ganesan, M
Thompson, KJ
McKillop, LH
Bautista, A
Bataller, R
French, SW
AF Neuman, Manuela G.
Malnick, Stephen
Maor, Yaakov
Nanau, Radu M.
Melzer, Ehud
Ferenci, Peter
Seitz, Helmut K.
Mueller, Sebastian
Mell, Haim
Samuel, Didier
Cohen, Lawrence B.
Kharbanda, Kusum K.
Osna, Natalia A.
Ganesan, Murali
Thompson, Kyle J.
McKillop, Lain H.
Bautista, Abraham
Bataller, Ramon
French, Samuel W.
TI Alcoholic liver disease: Clinical and translational research
SO EXPERIMENTAL AND MOLECULAR PATHOLOGY
LA English
DT Review
DE Alcoholic liver disease; Alcohol dehydrogenase; Betaine; CYP2E1;
Hepatocarcinogenesis; Liver fibrosis; Hepatitis B and C viral infection;
Human immunodeficiency virus; Liver transplant
ID HEPATITIS-C VIRUS; GENOTYPE 1 INFECTION; TREATMENT-NAIVE PATIENTS;
PEGYLATED INTERFERON-ALPHA; CACO-2 CELL MONOLAYER; CHRONIC HCV
INFECTION; ELEVATED S-ADENOSYLHOMOCYSTEINE; SUSTAINED VIROLOGICAL
RESPONSE; ACETALDEHYDE-INDUCED INCREASE; DACLATASVIR PLUS ASUNAPREVIR
AB The present review spans a broad spectrum of topics dealing with alcoholic liver disease (ALD), including clinical research, translational research, pathogenesis and therapies. A special accent is placed on alcohol misuse, as alcohol is a legally commercialized and taxable product. Drinking alcohol, particularly from a young age, is a major health problem. Alcoholism is known to contribute to morbidity and mortality. A systematic literature search was performed in order to obtain updated data (2008-2015). The review is focused on genetic polymorphisms of alcohol metabolizing enzymes and the role of cytochrome p450 2E1 and iron in ALD. Alcohol-mediated hepatocarcinogenesis is also discussed in the presence or absence of co-morbidities such as viral hepatitis C as well as therapeutic the role of innate immunity in ALD-HCV. Moreover, emphasis was placed on alcohol and drug interactions, as well as liver transplantation for end-stage ALD. Finally, the time came to eradicate alcohol-induced liver and intestinal damage by using betaine. (C) 2015 Elsevier Inc. All rights reserved.
C1 [Neuman, Manuela G.; Nanau, Radu M.] Vitro Drug Safety & Biotechnol, Toronto, ON, Canada.
[Neuman, Manuela G.] Univ Toronto, Fac Med, Dept Pharmacol & Toxicol, Toronto, ON, Canada.
[Malnick, Stephen; Maor, Yaakov; Melzer, Ehud] Hebrew Univ Jerusalem, Fac Med, Kaplan Hlth Sci Ctr, Dept Med,Div Gastroenterol, IL-76100 Rehovot, Israel.
[Ferenci, Peter] Med Univ Vienna, Vienna, Austria.
[Seitz, Helmut K.; Mueller, Sebastian] Heidelberg Univ, Heidelberg, Germany.
[Seitz, Helmut K.; Mueller, Sebastian] Salem Med Ctr, Alcohol Res Ctr, Dept Med Gastroenterol & Hepatol, Heidelberg, Germany.
[Mell, Haim] Israel Antidrug & Alcohol Author, Jerusalem, Israel.
[Samuel, Didier] Hop Paul Brousse, Ctr Hepatobiliaire, Res Inserm Paris Unit 785 11, Liver Transplant Unit, Paris, France.
[Cohen, Lawrence B.] Univ Toronto, Sunnybrook Hlth Sci Ctr, Div Gastroenterol, Toronto, ON, Canada.
[Cohen, Lawrence B.] Univ Toronto, Dept Internal Med, Toronto, ON, Canada.
[Kharbanda, Kusum K.; Osna, Natalia A.; Ganesan, Murali] Univ Nebraska Med Ctr, Vet Affairs Nebraska Western Iowa Hlth Care Syst, Res Serv, Omaha, NE USA.
[Thompson, Kyle J.; McKillop, Lain H.] Carolinas Med Ctr, Dept Surg, Charlotte, NC 28203 USA.
[Bautista, Abraham] NIAAA, Off Extramural Act, NIH, Rockville, MD 20852 USA.
[Bataller, Ramon] Univ N Carolina, Dept Med, Div Gastroenterol & Hepatol, Chapel Hill, NC USA.
[Bataller, Ramon] Univ N Carolina, Dept Nutr, Chapel Hill, NC USA.
[French, Samuel W.] Harbor UCLA Med Ctr, Torrance, CA 90509 USA.
RP Neuman, MG (reprint author), Banting & Best Inst, Dept Pharmacol & Toxicol Vitro Drug Safety & Biot, 100 Coll St,Lab 217, Toronto, ON M5G 0A3, Canada.
EM manuela.neuman@utoronto.ca
FU European Association for the Biological Research on Alcoholism (ESBRA);
In Vitro Drug Safety and Biotechnology; Mahaffy Innovative Grant,
Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada;
[5U01AA-021818-03]
FX The article is based upon the some of the presentations given at the
"7TH Charles Lieber Annual symposium: Alcohol and Chronic Diseases"
organized by M.G. Neuman, as a satellite symposium to the 38th Meeting
of the Research Society for Alcoholism, June 2015, San Antonio, Texas,
USA as well as International Symposium "Alcohol a New Challenge"
organized by M. G. Neuman, Y. Maor, E. Melzer and S. Malnick, January
2015, Kaplan Medical Center, Rehovot, Israel. We are grateful to the
European Association for the Biological Research on Alcoholism (ESBRA)
that sponsored two of our speakers for the Israeli Symposium and to
Debra Sharp, Director RSA for her ongoing support with Lieber's
satellite symposium. Dr. French thanks Adriana Flores for typing his
manuscript. Dr. French research on betaine was supported by
5U01AA-021818-03. The funding for the manuscript was provided by the In
Vitro Drug Safety and Biotechnology and Mahaffy Innovative Grant,
Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada.
NR 202
TC 6
Z9 6
U1 4
U2 17
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0014-4800
EI 1096-0945
J9 EXP MOL PATHOL
JI Exp. Mol. Pathol.
PD DEC
PY 2015
VL 99
IS 3
BP 596
EP 610
DI 10.1016/j.yexmp.2015.09.001
PG 15
WC Pathology
SC Pathology
GA CZ2SI
UT WOS:000366954500030
PM 26342547
ER
PT J
AU Schwimmer, JB
Lavine, JE
Neuschwander-Tetri, BA
Wilson, L
Xanthakos, SA
Barlow, SE
Vos, MB
Molleston, JP
Whitington, PF
Rosenthal, P
Jain, AK
Murray, KF
Brunt, EM
Kleiner, DE
Van Natta, ML
Clark, JM
Tonascia, J
Doo, E
AF Schwimmer, Jeffrey B.
Lavine, Joel E.
Neuschwander-Tetri, Brent A.
Wilson, Laura
Xanthakos, Stavra A.
Barlow, Sarah E.
Vos, Miriam B.
Molleston, Jean P.
Whitington, Peter F.
Rosenthal, Philip
Jain, Ajay K.
Murray, Karen F.
Brunt, Elizabeth M.
Kleiner, David E.
Van Natta, Mark L.
Clark, Jeanne M.
Tonascia, James
Doo, Edward
TI Cysteamine Bitartrate Delayed-Release (DR) for the Treatment of
Nonalcoholic Fatty Liver Disease (NAFLD) in Children (CyNCh) Trial
SO HEPATOLOGY
LA English
DT Meeting Abstract
C1 [Schwimmer, Jeffrey B.] Univ Calif San Diego, Pediat, San Diego, CA USA.
[Schwimmer, Jeffrey B.] Rady Childrens Hosp, Gastroenterol, San Diego, CA USA.
[Lavine, Joel E.] Columbia Univ, Pediat, New York, NY USA.
[Neuschwander-Tetri, Brent A.] St Louis Univ, Med, St Louis, MO 63103 USA.
[Wilson, Laura; Van Natta, Mark L.; Tonascia, James] Johns Hopkins, Sch Publ Hlth, Baltimore, MD USA.
[Xanthakos, Stavra A.] Cincinnati Childrens Hosp, Pediat, Cincinnati, OH USA.
[Barlow, Sarah E.] Texas Childrens Hosp, Pediat, Houston, TX 77030 USA.
[Molleston, Jean P.] James Whitcomb Riley Hosp Children, Pediat, Indianapolis, IN 46202 USA.
[Whitington, Peter F.] Ann & Robert H Lurie Childrens Hosp Chicago, Pediat, Chicago, IL 60611 USA.
[Rosenthal, Philip] UCSF, Pediat, San Francisco, CA USA.
[Jain, Ajay K.] St Louis Univ, Pediat, St Louis, MO 63103 USA.
[Murray, Karen F.] Seattle Childrens Hosp, Pediat, Seattle, WA USA.
[Brunt, Elizabeth M.] Washington Univ, Pathol, St Louis, MO USA.
[Kleiner, David E.] NCI, Pathol, Bethesda, MD 20892 USA.
[Clark, Jeanne M.] Johns Hopkins Univ, Med, Baltimore, MD USA.
[Doo, Edward] NIDDK, Liver Dis, Bethesda, MD 20892 USA.
[Vos, Miriam B.] Emory Univ, Pediat, Atlanta, GA 30322 USA.
NR 0
TC 1
Z9 1
U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0270-9139
EI 1527-3350
J9 HEPATOLOGY
JI Hepatology
PD DEC
PY 2015
VL 62
IS 6
MA LB-31
BP 1398A
EP 1399A
PG 2
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA CZ3OF
UT WOS:000367013200032
ER
PT J
AU Sehgal, R
Patra, S
David, P
Vyas, A
Khanam, A
Hissar, S
Gupta, E
Kumar, G
Kottilil, S
Maiwall, R
Sarin, SK
Trehanpati, N
AF Sehgal, Rashi
Patra, Sharda
David, Paul
Vyas, Ashish
Khanam, Arshi
Hissar, Syed
Gupta, Ekta
Kumar, Guresh
Kottilil, Shyam
Maiwall, Rakhi
Sarin, Shiv Kumar
Trehanpati, Nirupama
TI Impaired Monocyte-Macrophage Functions and Defective Toll-Like Receptor
Signaling in Hepatitis E Virus-Infected Pregnant Women With Acute Liver
Failure
SO HEPATOLOGY
LA English
DT Article
ID VIRAL-HEPATITIS; IFN-GAMMA; C VIRUS; INJURY; PATHOGENESIS; ACTIVATION;
MORTALITY; DISEASE; CELLS; INDIA
AB Acute viral hepatitis resulting due to hepatitis E viral infection (AVH-E) is often serious in pregnancy and could result in acute liver failure (ALF). The role of monocytes and macrophages (mono-macs) in the pathogenesis of AVH-E and development of ALF-E in pregnancy is unclear. We investigated the functions of mono-macs in pregnant (P), AVH-E (n = 44), ALF-E (n = 12), healthy controls (HC; n = 20) and compared with nonpregnant (NP) AVHE (n = 10), ALF-E (n = 5), and HC (n = 10). We also recruited non-hepatitis E virus-related pregnant (P), ALF-NE (n = 5) and non-pregnant (NP), ALF-NE (n = 12) patients with ALF. Mono-macs, dendritic cell (DC) phenotypes, and Toll-like receptor (TLR) expressions were studied by flow cytometry and reverse-transcriptase polymerase chain reaction. Mono-macs functionality was determined by analyzing their phagocytic activity and reactive oxygen species (ROS) generation by using flow cytometry. Frequency of mono-macs and DCs was increased during HEV infection compared to HC (P < 0.001). Macrophages were increased (P < 0.002) in ALF-E(P) compared to ALF-NE(P). The macrophage phagocytic activity and Escherichia coli-induced ROS production was significantly impaired in ALF-E(P) compared to AVH-E(P) (P < 0.001), ALF-E(NP), and ALF-NE(P) patients (P < 0.02). TLR3 and TLR9 expression and downstream MYD88 signalling molecules IRF3 and IRF7 were significantly down-regulated in ALF-E(P) (P < 0.00) compared to AVH-E(P) and ALF-NE(P). Conclusion: Functionality of mono-macs is impaired in pregnant ALF-E patients compared to AVH-E(P). Reduced TLR3 and TLR7 expression and TLR downstream-signaling molecules in pregnant ALF-E patients suggests inadequate triggers for the innate immune responses contributing to development and severity of ALF-E. Studies using TLR agonists to activate mono-macs may be of use and in vitro studies should be undertaken using patient samples.
C1 [Sehgal, Rashi; David, Paul; Vyas, Ashish; Khanam, Arshi; Hissar, Syed; Kumar, Guresh; Sarin, Shiv Kumar; Trehanpati, Nirupama] Inst Liver & Biliary Sci, Dept Res, New Delhi 110070, India.
[Gupta, Ekta] Inst Liver & Biliary Sci, Dept Virol, New Delhi 110070, India.
[Maiwall, Rakhi; Sarin, Shiv Kumar] Inst Liver & Biliary Sci, Dept Hepatol, New Delhi 110070, India.
[Patra, Sharda] Lady Harding Med Coll, Gynecol & Obstet, New Delhi, India.
[Kottilil, Shyam] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA.
RP Trehanpati, N (reprint author), Inst Liver & Biliary Sci, D-1, New Delhi 110070, India.
EM shivsarin@gmail.com; trehanpati@gmail.com
FU Indian Council of Medical Research, Government of India, New Delhi
[VIR/17/2009/ECD-1]; National Institute of Allergy and Infectious
Diseases, National Institutes of Health, Bethesda, MD
FX This study was funded by HEV grant no. VIR/17/2009/ECD-1 received from
the Indian Council of Medical Research, Government of India, New Delhi
and partially by the intramural program of the National Institute of
Allergy and Infectious Diseases, National Institutes of Health,
Bethesda, MD.
NR 40
TC 7
Z9 7
U1 0
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0270-9139
EI 1527-3350
J9 HEPATOLOGY
JI Hepatology
PD DEC
PY 2015
VL 62
IS 6
BP 1683
EP 1696
DI 10.1002/hep.28143
PG 14
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA CZ3OF
UT WOS:000367013200041
PM 26331854
ER
PT J
AU Kwan, R
Chen, L
Looi, K
Tao, GZ
Weerasinghe, SV
Snider, NT
Conti, MA
Adelstein, RS
Xie, Q
Omary, MB
AF Kwan, Raymond
Chen, Lu
Looi, Koksun
Tao, Guo-Zhong
Weerasinghe, Sujith V.
Snider, Natasha T.
Conti, Mary Anne
Adelstein, Robert S.
Xie, Qing
Omary, M. Bishr
TI PKC412 Normalizes Mutation-Related Keratin Filament Disruption and
Hepatic Injury in Mice by Promoting Keratin-Myosin Binding
SO HEPATOLOGY
LA English
DT Article
ID EPIDERMOLYSIS-BULLOSA SIMPLEX; SIMPLE EPITHELIAL KERATINS; ACUTE
MYELOID-LEUKEMIA; LAMIN A/C GENE; TRANSGENIC MICE;
INTERMEDIATE-FILAMENTS; DISEASE; INHIBITION; FRAGILITY; ACTIVATION
AB Keratins, among other cytoskeletal intermediate filament proteins, are mutated at a highly conserved arginine with consequent severe disease phenotypes due to disruption of keratin filament organization. We screened a kinase inhibitor library, using A549 cells that are transduced with a lentivirus keratin 18 (K18) construct, to identify compounds that normalize filament disruption due to K18 Arg90Cys mutation at the conserved arginine. High-throughput screening showed that PKC412, a multikinase inhibitor, ameliorated K18 Arg90Cys-mediated keratin filament disruption in cells and in the livers of previously described transgenic mice that overexpress K18 Arg90Cys. Furthermore, PKC412 protected cultured A549 cells that express mutant or wild-type K18 and mouse livers of the K18 Arg90Cys-overexpressing transgenic mice from Fas-induced apoptosis. Proteomic analysis of proteins that associated with keratins after exposure of K18-expressing A549 cells to PKC412 showed that nonmuscle myosin heavy chain-IIA (NMHC-IIA) partitions with the keratin fraction. The nonmuscle myosin-IIA (NM-IIA) association with keratins was confirmed by immune staining and by coimmunoprecipitation. The keratin-myosin association is myosin dephosphorylation-dependent; occurs with K8, the obligate K18 partner; is enhanced by PKC412 in cells and mouse liver; and is blocked by hyperphosphorylation conditions in cultured cells and mouse liver. Furthermore, NMHC-IIA knockdown inhibits PKC412-mediated normalization of K18 R90C filaments. Conclusion: The inhibitor PKC412 normalizes K18 Arg90Cys mutation-induced filament disruption and disorganization by enhancing keratin association with NM-IIA in a myosin dephosphorylation-regulated manner. Targeting of intermediate filament disorganization by compounds that alter keratin interaction with their associated proteins offers a potential novel therapeutic approach for keratin and possibly other intermediate filament protein-associated diseases.
C1 [Kwan, Raymond; Chen, Lu; Looi, Koksun; Weerasinghe, Sujith V.; Snider, Natasha T.; Omary, M. Bishr] Univ Michigan, Dept Mol & Integrat Physiol, Ann Arbor, MI 48109 USA.
[Kwan, Raymond; Chen, Lu; Looi, Koksun; Weerasinghe, Sujith V.; Snider, Natasha T.; Omary, M. Bishr] Univ Michigan, Dept Med, Ann Arbor, MI 48109 USA.
[Kwan, Raymond; Omary, M. Bishr] VA Ann Arbor Healthcare Syst, Ann Arbor, MI USA.
[Chen, Lu; Xie, Qing] Shanghai Jiao Tong Univ, Dept Infect Dis, Ruijin Hosp, Sch Med, Shanghai 200030, Peoples R China.
[Tao, Guo-Zhong] Stanford Univ, Dept Surg, Palo Alto, CA 94304 USA.
[Conti, Mary Anne; Adelstein, Robert S.] NHLBI, Mol Cardiol Lab, NIH, Bethesda, MD 20892 USA.
RP Omary, MB (reprint author), 1137 E Catherine St,7744 MSII, Ann Arbor, MI 48109 USA.
EM xieqingrjh@163.com; mbishr@med.umich.edu
OI Adelstein, Robert/0000-0002-8683-2144
FU National Institutes of Health [R01 DK47918, K01 DK093776]; Department of
Veterans Affairs; China Scholarship Council; institutional National
Institutes of Health grant [DK34933]
FX Supported by National Institutes of Health grants R01 DK47918 (to
M.B.O.) and K01 DK093776 (to N.T.S.), the Department of Veterans Affairs
(to M.B.O.), the China Scholarship Council (to L.C.), and institutional
National Institutes of Health grant DK34933 to the University of
Michigan.
NR 33
TC 2
Z9 2
U1 1
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0270-9139
EI 1527-3350
J9 HEPATOLOGY
JI Hepatology
PD DEC
PY 2015
VL 62
IS 6
BP 1858
EP 1869
DI 10.1002/hep.27965
PG 12
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA CZ3OF
UT WOS:000367013200056
PM 26126491
ER
PT J
AU Liang, TJ
Block, TM
McMahon, BJ
Ghany, MG
Urban, S
Guo, JT
Locarnini, S
Zoulim, F
Chang, KM
Lok, AS
AF Liang, T. Jake
Block, Timothy M.
McMahon, Brian J.
Ghany, Marc G.
Urban, Stephan
Guo, Ju-Tao
Locarnini, Stephen
Zoulim, Fabien
Chang, Kyong-Mi
Lok, Anna S.
TI Present and Future Therapies of Hepatitis B: From Discovery to Cure
SO HEPATOLOGY
LA English
DT Review
ID CLOSED CIRCULAR DNA; TENOFOVIR DISOPROXIL FUMARATE; TAUROCHOLATE
COTRANSPORTING POLYPEPTIDE; COMPLEX THERAPEUTIC VACCINE; CHIMERIC
ANTIGEN RECEPTOR; ANTIVIRAL IMMUNE-RESPONSE; LARGE SURFACE PROTEIN; D
VIRUS ENTRY; T-CELLS; IN-VIVO
AB Hepatitis B virus (HBV) is a significant global pathogen, infecting more than 240 million people worldwide. While treatment for HBV has improved, HBV patients often require lifelong therapies and cure is still a challenging goal. Recent advances in technologies and pharmaceutical sciences have heralded a new horizon of innovative therapeutic approaches that are bringing us closer to the possibility of a functional cure of chronic HBV infection. In this article, we review the current state of science in HBV therapy and highlight new and exciting therapeutic strategies spurred by recent scientific advances. Some of these therapies have already entered into clinical phase, and we will likely see more of them moving along the development pipeline. Conclusion: With growing interest in developing and efforts to develop more effective therapies for HBV, the challenging goal of a cure may be well within reach in the near future.
C1 [Liang, T. Jake; Ghany, Marc G.] NIDDK, LDB, NIH, Bethesda, MD 20892 USA.
[Block, Timothy M.] Baruch S Blumberg Inst, Doylestown, PA USA.
[McMahon, Brian J.] Ctr Dis Control & Prevent, Natl Ctr Emerging & Zoonot Infect Dis, Anchorage, AK USA.
[Urban, Stephan] Univ Heidelberg Hosp, Mol Virol, Dept Infect Dis, Heidelberg, Germany.
[Urban, Stephan] Univ Heidelberg Hosp, German Ctr Infect Dis, Heidelberg, Germany.
[Locarnini, Stephen] Lyon Univ, Hepatol Dept, Lyon, France.
[Locarnini, Stephen] Canc Res Ctr Lyon, INSERM, U1052, Lyon, France.
[Zoulim, Fabien] Doherty Inst, Victorian Infect Dis Reference Lab, Melbourne, Vic, Australia.
[Chang, Kyong-Mi] Philadelphia Vet Affairs Med Ctr, Dept Med, Philadelphia, PA USA.
[Chang, Kyong-Mi] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Lok, Anna S.] Univ Michigan, Div Gastroenterol & Hepatol, Ann Arbor, MI 48109 USA.
RP Liang, TJ (reprint author), NIDDK, LDB, NIH, Bldg 10-9B16,10 Ctr Dr, Bethesda, MD 20892 USA.
EM jliang@nih.gov
FU Janssen; Oncore-Tekmira; Gilead; Bristol-Myers Squibb; Roche; Novira;
Arrowhead
FX Dr. Guo received grants from Janssen. Dr. Block is on the Board of and
owns stock in Contravir. He received grants and holds intellectual
property rights with Oncore-Tekmira. Dr. Lok consults and received
grants from Gilead. She consults from GlaxoSmithKline, Merck, MYR, and
Tekmira. She received grants from Bristol-Myers Squibb. Dr. Chang
advises Genentech, Arbutus, and Alnylam. Dr. Zoulim consults and
received grants from Roche, Gilead, and Novira. He consults for Janssen.
Dr. Locarnini received royalties and holds intellectual property rights
with Melbourne Health. He consults and received fees from Arrowhead. He
consults for Gilead.
NR 154
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U1 6
U2 25
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0270-9139
EI 1527-3350
J9 HEPATOLOGY
JI Hepatology
PD DEC
PY 2015
VL 62
IS 6
BP 1893
EP 1908
DI 10.1002/hep.28025
PG 16
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA CZ3OF
UT WOS:000367013200059
PM 26239691
ER
PT J
AU Mezey, E
Nemeth, K
AF Mezey, Eva
Nemeth, Krisztian
TI Mesenchymal stem cells and infectious diseases: Smarter than drugs
SO IMMUNOLOGY LETTERS
LA English
DT Article
DE MSC; BMSC; Immune-regulatory effects of MSC; MSC and pathogen
interactions
ID TOLL-LIKE RECEPTORS; INDUCED ACUTE LUNG; STAPHYLOCOCCUS-AUREUS
INFECTION; STROMAL CELLS; IN-VITRO; EX-VIVO; EXPERIMENTAL COLITIS;
BACTERIAL CLEARANCE; IMMUNE-RESPONSES; HBV INFECTION
AB After bone marrow stromal cells (BMSCs also known as mesenchymal stem cells of bone marrow origin) were used successfully to treat graft versus host disease in a single human subject [1], many investigators studied the immune-suppressive properties of BMSCs and later adipose tissue derived MSCs (AMSC). The field has expanded significantly and there are many ongoing clinical trials that are trying to exploit the amazing abilities of MSCs from many tissues to regulate the immune system. In addition to "supervising" cells of the innate immune system, MSCs have also been shown to have anti-microbial properties. They appear to make molecules with direct effects on bacteria. Many questions about MSCs remain, however. We still need to determine how to isolate subpopulations of cells with specific immunomodulatory or antibacterial actions from the heterogeneous pool of cultured BMSCs. We need to find ways to prime cells to improve their immune regulatory activities, and while we have some ideas about mechanisms that underlie MSC/immune cell interactions, there is still much to discover before we can take full advantage of the regulatory abilities of MSCs to treat human diseases. (C) 2015 Published by Elsevier B.V.
C1 [Mezey, Eva; Nemeth, Krisztian] Natl Inst Dent & Craniofacial Res, Adult Stem Cell Sect, Craniofacial & Skeletal Dis Branch, NIH,Hlth & Human Serv, Bethesda, MD 20892 USA.
[Nemeth, Krisztian] Semmelweis Univ, Dept Dermatol, H-1085 Budapest, Hungary.
RP Mezey, E (reprint author), Natl Inst Dent & Craniofacial Res, Adult Stem Cell Sect, Craniofacial & Skeletal Dis Branch, NIH,Hlth & Human Serv, Bethesda, MD 20892 USA.
EM mezeye@mail.nih.gov; nemethk@mail.nih.gov
FU Division of Intramural Research program of NIDCR, Intramural Research
Program, NIH, DHHS [ZIA DE000714, ZIA DE000676]
FX Work in the authors' laboratory is supported by the Division of
Intramural Research program of NIDCR (ZIA DE000714 and ZIA DE000676), in
the Intramural Research Program, NIH, DHHS.
NR 89
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Z9 1
U1 3
U2 11
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0165-2478
EI 1879-0542
J9 IMMUNOL LETT
JI Immunol. Lett.
PD DEC
PY 2015
VL 168
IS 2
SI SI
BP 208
EP 214
DI 10.1016/j.imlet.2015.05.020
PG 7
WC Immunology
SC Immunology
GA CZ5BE
UT WOS:000367116300013
PM 26051681
ER
PT J
AU Jiang, MS
Yang, XY
Esposito, D
Nelson, E
Yuan, JH
Hopkins, RF
Broadt, T
Xiao, Z
Colantonio, S
Prieto, DA
Welch, AR
Creekmore, SP
Mitra, G
Zhu, JW
AF Jiang, Man-Shiow
Yang, Xiaoyi
Esposito, Dominic
Nelson, Earl
Yuan, Jinhui
Hopkins, Ralph F.
Broadt, Trevor
Xiao, Zhen
Colantonio, Simona
Prieto, DaRue A.
Welch, Anthony R.
Creekmore, Stephen P.
Mitra, George
Zhu, Jianwei
TI Mammalian cell transient expression, non-affinity purification, and
characterization of human recombinant IGFBP7, an IGF-1 targeting
therapeutic protein
SO INTERNATIONAL IMMUNOPHARMACOLOGY
LA English
DT Article
DE IGFBP7; Protein expression; Protein purification; Transient gene
expression
ID GENE-EXPRESSION; HEPATOCELLULAR-CARCINOMA; SECRETED PROTEIN; GROWTH;
TRANSFECTION; SENESCENCE; LEVEL
AB Targeted inhibiting insulin-like growth factor 1 is an effective approach for cancer therapy. Insulin-like growth factor binding protein 7 (IGFBP7) is considered as a potential therapeutic protein. However, producing high quality of such non-IgG proteins in mammalian cells is still a challenge in biopharmaceutical development Here, we report a rapid production process by using transient gene transfection in HEK 293E cells. A set of constructs combining several expression promoters, leader sequences, and 5' un-translated regions were generated and optimized, from which the best vector with expression level at similar to 50 mg/L was selected for production at 2 L cell culture scale. Comparison study in downstream purification methods led to development of a scalable, non-affinity chromatography strategy through Super Q Fast Flow Q and Heparin columns. The product was characterized in purity (99%), isoelectric point, molecule weight, glycosylation, and stability by using SEC-HPLC, SDS-PAGE, isoelectric focusing and mass spectrometry. The highly purified product shows IGF-1 binding activity and inhibits IGF-1-induced cell proliferation. This process not only provides a remarkable high expression at similar to 50 mg/L and pure glycosylated mammalian rhIGFBP7, also highlights that transient gene expression technology is practical to be used for production and early development of recombinant non-IgG therapeutic proteins. (C) 2015 Elsevier B.V. All rights reserved.
C1 [Jiang, Man-Shiow; Yang, Xiaoyi; Nelson, Earl; Yuan, Jinhui; Broadt, Trevor; Mitra, George; Zhu, Jianwei] Frederick Natl Lab Canc Res, Leidos Biomed Res Inc, Biopharmaceut Dev Program, Frederick, MD 21702 USA.
[Esposito, Dominic; Hopkins, Ralph F.] Frederick Natl Lab Canc Res, Leidos Biomed Res Inc, Prot Express Lab, Canc Res Technol Program, Frederick, MD 21702 USA.
[Xiao, Zhen; Colantonio, Simona; Prieto, DaRue A.] Frederick Natl Lab Canc Res, Leidos Biomed Res Inc, Prot Characterizat Lab, Canc Res Technol Program, Frederick, MD 21702 USA.
[Welch, Anthony R.; Creekmore, Stephen P.] Natl Canc Inst, Biol Resources Branch, Frederick, MD 21702 USA.
RP Zhu, JW (reprint author), Frederick Natl Lab Canc Res, Leidos Biomed Res Inc, Biopharmaceut Dev Program, Frederick, MD 21702 USA.
EM jianweiz@sjtu.edu.cn
FU National Cancer Institute, National Institutes of Health
[HHSN261200800001E]; Developmental Therapeutics Program in the Division
of Cancer Treatment and Diagnosis of the National Cancer Institute
[HHSN261200800001E]
FX The authors would like to express acknowledgment to Dr. M. Green for his
expression plasmid from where we amplified the IGFBP7 cDNA. This project
has been funded in whole or in part with federal funds from the National
Cancer Institute, National Institutes of Health, under Contract No.
HHSN261200800001E. The content of this publication does not necessarily
reflect the views or policies of the Department of Health and Human
Services, nor does mention of trade names, commercial products, or
organizations imply endorsement by the U.S. Government This research was
supported [in part] by the Developmental Therapeutics Program in the
Division of Cancer Treatment and Diagnosis of the National Cancer
Institute (Contract No. HHSN261200800001E).
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U1 0
U2 4
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1567-5769
EI 1878-1705
J9 INT IMMUNOPHARMACOL
JI Int. Immunopharmacol.
PD DEC
PY 2015
VL 29
IS 2
BP 476
EP 487
DI 10.1016/j.intimp.2015.10.008
PG 12
WC Immunology; Pharmacology & Pharmacy
SC Immunology; Pharmacology & Pharmacy
GA CY9ZL
UT WOS:000366764800031
PM 26474694
ER
PT J
AU Arai, AE
AF Arai, Andrew E.
TI Fuzzy or Sharp Borders of Acute Myocardial Ischemia and Infarction?
SO JACC-CARDIOVASCULAR IMAGING
LA English
DT Editorial Material
DE acute myocardial infarction; gadolinium; MRI; myocardial ischemia
ID BLOOD-FLOW; RISK; AREA; OCCLUSION; SIZE; DOGS
C1 [Arai, Andrew E.] NHLBI, Adv Cardiovasc Imaging, NIH, Bethesda, MD 20892 USA.
RP Arai, AE (reprint author), NHLBI, Adv Cardiovasc Imaging, NIH, Bldg 10,Room B1D416,MSC 1061,10 Ctr Dr, Bethesda, MD 20892 USA.
EM araia@nih.gov
FU Intramural NIH HHS; NHLBI NIH HHS [HL006136]
NR 9
TC 0
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U1 1
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1936-878X
EI 1876-7591
J9 JACC-CARDIOVASC IMAG
JI JACC-Cardiovasc. Imag.
PD DEC
PY 2015
VL 8
IS 12
BP 1390
EP 1392
DI 10.1016/j.jcmg.2015.10.003
PG 3
WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical
Imaging
SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine &
Medical Imaging
GA CZ6IS
UT WOS:000367205100006
PM 26699108
ER
PT J
AU Dunn, BK
Steele, VE
Fagerstrom, RM
Topp, CF
Ransohoff, D
Cunningham, C
Lubet, R
Ford, LG
Kramer, BS
AF Dunn, Barbara K.
Steele, Vernon E.
Fagerstrom, Richard M.
Topp, Carol F.
Ransohoff, David
Cunningham, Christopher
Lubet, Ron
Ford, Leslie G.
Kramer, Barnett S.
TI Predictive Value Tools as an Aid in Chemopreventive Agent Development
SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Article
ID DRUG DEVELOPMENT; RATES
AB Background: Over 25 years, the National Cancer Institute's Division of Cancer Prevention has entered some 800 agents into a chemopreventive agent testing program. Two critical steps involve: 1) in vitro/in vivo morphologic assays and 2) animal tumor assays (incidence/multiplicity reduction). We sought to determine how accurately the earlier-stage (morphologic) assays predict efficacy in the later-stage (animal tumor) assays.
Methods: Focusing on 210 agents tested in both morphologic and animal tumor assays, we carried out statistical modeling of how well the six most commonly used morphologic assays predicted drug efficacy in animal tumor assays. Using multimodel inference, three statistical models were generated to evaluate the ability of these six morphologic assays to predict tumor outcomes in three different sets of animal tumor assays: 1) all tumor types, 2) mammary cancer only, and 3) colon cancer only. Using this statistical modeling approach, each morphologic assay was assigned a value reflecting how strongly it predicted outcomes in each of the three different sets of animal tumor assays.
Results: We demonstrated differences in the predictive value of specific morphologic assays for positive animal tumor assay results. Some of the morphologic assays were strongly predictive of meaningful positive efficacy outcomes in animal tumor assays representing specific cancer types, particularly the aberrant crypt focus (ACF) assay for colon cancer. Moreover, less strongly predictive assays can be combined and sequenced, resulting in enhanced composite predictive ability.
Conclusions: Predictive models such as these could be used to guide selection of preventive agents as well as morphologic and animal tumor assays, thereby improving the efficiency of our approach to chemopreventive agent development.
C1 [Dunn, Barbara K.; Steele, Vernon E.; Fagerstrom, Richard M.; Lubet, Ron; Ford, Leslie G.; Kramer, Barnett S.] NCI, Canc Prevent Div, Bethesda, MD 20892 USA.
[Topp, Carol F.] CCS Associates Inc, Mclean, VA USA.
[Ransohoff, David] Univ N Carolina, Dept Med, Chapel Hill, NC USA.
[Cunningham, Christopher] Informat Management Serv Inc, Rockville, MD USA.
RP Dunn, BK (reprint author), NCI, Canc Prevent Div, 9609 Med Ctr Dr,Room 5E534, Bethesda, MD 20892 USA.
EM dunnb@mail.nih.gov
NR 8
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U1 0
U2 0
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 DEC
PY 2015
VL 107
IS 12
AR djv259
DI 10.1093/jnci/djv259
PG 8
WC Oncology
SC Oncology
GA CZ2YN
UT WOS:000366970900004
PM 26420882
ER
PT J
AU Sampson, JN
Wheeler, WA
Yeager, M
Panagiotou, O
Wang, Z
Berndt, SI
Lan, Q
Abnet, CC
Amundadottir, LT
Figueroa, JD
Landi, MT
Mirabello, L
Savage, SA
Taylor, PR
De Vivo, I
McGlynn, KA
Purdue, MP
Rajaraman, P
Adami, HO
Ahlbom, A
Albanes, D
Amary, MF
An, SJ
Andersson, U
Andriole, G
Andrulis, IL
Angelucci, E
Ansell, SM
Arici, C
Armstrong, BK
Arslan, AA
Austin, MA
Baris, D
Barkauskas, DA
Bassig, BA
Becker, N
Benavente, Y
Benhamou, S
Berg, C
Van Den Berg, D
Bernstein, L
Bertrand, KA
Birmann, BM
Black, A
Boeing, H
Boffetta, P
Boutron-Ruault, MC
Bracci, PM
Brinton, L
Brooks-Wilson, AR
Bueno-De-Mesquita, HB
Burdett, L
Buring, J
Butler, MA
Cai, QY
Cancel-Tassin, G
Canzian, F
Carrato, A
Carreon, T
Carta, A
Chan, JKC
Chang, ET
Chang, GC
Chang, IS
Chang, J
Chang-Claude, J
Chen, CJ
Chen, CY
Chen, C
Chen, CH
Chen, C
Chen, HY
Chen, KX
Chen, KY
Chen, KC
Chen, Y
Chen, YH
Chen, YS
Chen, YM
Chien, LH
Chirlaque, MD
Choi, JE
Choi, YY
Chow, WH
Chung, CC
Clavel, J
Clavel-Chapelon, F
Cocco, P
Colt, JS
Comperat, E
Conde, L
Connors, JM
Conti, D
Cortessis, VK
Cotterchio, M
Cozen, W
Crouch, S
Crous-Bou, M
Cussenot, O
Davis, FG
Ding, T
Diver, WR
Dorronsoro, M
Dossus, L
Duell, EJ
Ennas, MG
Erickson, RL
Feychting, M
Flanagan, AM
Foretova, L
Fraumeni, JF
Freedman, ND
Freeman, LEB
Fuchs, C
Gago-Dominguez, M
Gallinger, S
Gao, YT
Gapstur, SM
Garcia-Closas, M
Garcia-Closas, R
Gascoyne, RD
Gastier-Foster, J
Gaudet, MM
Gaziano, JM
Giffen, C
Giles, GG
Giovannucci, E
Glimelius, B
Goggins, M
Gokgoz, N
Goldstein, AM
Gorlick, R
Gross, M
Grubb, R
Gu, J
Guan, P
Gunter, M
Guo, H
Habermann, TM
Haiman, CA
Halai, D
Hallmans, G
Hassan, M
Hattinger, C
He, QC
He, XZ
Helzlsouer, K
Henderson, B
Henriksson, R
Hjalgrim, H
Hoffman-Bolton, J
Hohensee, C
Holford, TR
Holly, EA
Hong, YC
Hoover, RN
Horn-Ross, PL
Hosain, GMM
Hosgood, HD
Hsiao, CF
Hu, N
Hu, W
Hu, ZB
Huang, MS
Huerta, JM
Hung, JY
Hutchinson, A
Inskip, PD
Jackson, RD
Jacobs, EJ
Jenab, M
Jeon, HS
Ji, BT
Jin, GF
Jin, L
Johansen, C
Johnson, A
Jung, YJ
Kaaks, R
Kamineni, A
Kane, E
Kang, CH
Karagas, MR
Kelly, RS
Khaw, KT
Kim, C
Kim, HN
Kim, JH
Kim, JS
Kim, YH
Kim, YT
Kim, YC
Kitahara, CM
Klein, AP
Klein, RJ
Kogevinas, M
Kohno, T
Kolonel, LN
Kooperberg, C
Kricker, A
Krogh, V
Kunitoh, H
Kurtz, RC
Kweon, SS
LaCroix, A
Lawrence, C
Lecanda, F
Lee, VHF
Li, DH
Li, HX
Li, JH
Li, YJ
Li, YQ
Liao, LM
Liebow, M
Lightfoot, T
Lim, WY
Lin, CC
Lin, DX
Lindstrom, S
Linet, MS
Link, BK
Liu, CW
Liu, JJ
Liu, L
Ljungberg, B
Lloreta, J
Di Lollo, S
Lu, D
Lund, E
Malats, N
Mannisto, S
Le Marchand, L
Marina, N
Masala, G
Mastrangelo, G
Matsuo, K
Maynadie, M
Mckay, J
McKean-Cowdin, R
Melbye, M
Melin, BS
Michaud, DS
Mitsudomi, T
Monnereau, A
Montalvan, R
Moore, LE
Mortensen, LM
Nieters, A
North, KE
Novak, AJ
Oberg, AL
Offit, K
Oh, IJ
Olson, SH
Palli, D
Pao, W
Park, IK
Park, JY
Park, KH
Patino-Garcia, A
Pavanello, S
Peeters, PHM
Perng, RP
Peters, U
Petersen, GM
Picci, P
Pike, MC
Porru, S
Prescott, J
Prokunina-Olsson, L
Qian, B
Qiao, YL
Rais, M
Riboli, E
Riby, J
Risch, HA
Rizzato, C
Rodabough, R
Roman, E
Roupret, M
Ruder, AM
de Sanjose, S
Scelo, G
Schned, A
Schumacher, F
Schwartz, K
Schwenn, M
Scotlandi, K
Seow, A
Serra, C
Serra, M
Sesso, HD
Setiawan, VW
Severi, G
Severson, RK
Shanafelt, TD
Shen, HB
Shen, W
Shin, MH
Shiraishi, K
Shu, XO
Siddiq, A
Sierrasesumaga, L
Sihoe, ADL
Skibola, CF
Smith, A
Smith, MT
Southey, MC
Spinelli, JJ
Staines, A
Stampfer, M
Stern, MC
Stevens, VL
Stolzenberg-Solomon, RS
Su, J
Su, WC
Sund, M
Sung, JS
Sung, SW
Tan, W
Tang, W
Tardon, A
Thomas, D
Thompson, CA
Tinker, LF
Tirabosco, R
Tjonneland, A
Travis, RC
Trichopoulos, D
Tsai, FY
Tsai, YH
Tucker, M
Turner, J
Vajdic, CM
Vermeulen, RCH
Villano, DJ
Vineis, P
Virtamo, J
Visvanathan, K
Wactawski-Wende, J
Wang, CY
Wang, CL
Wang, JC
Wang, JW
Wei, FS
Weiderpass, E
Weiner, GJ
Weinstein, S
Wentzensen, N
White, E
Witzig, TE
Wolpin, BM
Wong, MP
Wu, C
Wu, GP
Wu, JJ
Wu, TC
Wu, W
Wu, XF
Wu, YL
Wunder, JS
Xiang, YB
Xu, J
Xu, P
Yang, PC
Yang, TY
Ye, YQ
Yin, ZH
Yokota, J
Yoon, HI
Yu, CJ
Yu, H
Yu, K
Yuan, JM
Zelenetz, A
Zeleniuch-Jacquotte, A
Zhang, XC
Zhang, YW
Zhao, XY
Zhao, ZH
Zheng, H
Zheng, TZ
Zheng, W
Zhou, BS
Zhu, M
Zucca, M
Boca, SM
Cerhan, JR
Ferri, GM
Hartge, P
Hsiung, CA
Magnani, C
Miligi, L
Morton, LM
Smedby, KE
Teras, LR
Vijai, J
Wang, SS
Brennan, P
Caporaso, NE
Hunter, DJ
Kraft, P
Rothman, N
Silverman, DT
Slager, SL
Chanock, SJ
Chatterjee, N
AF Sampson, Joshua N.
Wheeler, William A.
Yeager, Meredith
Panagiotou, Orestis
Wang, Zhaoming
Berndt, Sonja I.
Lan, Qing
Abnet, Christian C.
Amundadottir, Laufey T.
Figueroa, Jonine D.
Landi, Maria Teresa
Mirabello, Lisa
Savage, Sharon A.
Taylor, Philip R.
De Vivo, Immaculata
McGlynn, Katherine A.
Purdue, Mark P.
Rajaraman, Preetha
Adami, Hans-Olov
Ahlbom, Anders
Albanes, Demetrius
Amary, Maria Fernanda
An, She-Juan
Andersson, Ulrika
Andriole, Gerald, Jr.
Andrulis, Irene L.
Angelucci, Emanuele
Ansell, Stephen M.
Arici, Cecilia
Armstrong, Bruce K.
Arslan, Alan A.
Austin, Melissa A.
Baris, Dalsu
Barkauskas, Donald A.
Bassig, Bryan A.
Becker, Nikolaus
Benavente, Yolanda
Benhamou, Simone
Berg, Christine
Van Den Berg, David
Bernstein, Leslie
Bertrand, Kimberly A.
Birmann, Brenda M.
Black, Amanda
Boeing, Heiner
Boffetta, Paolo
Boutron-Ruault, Marie-Christine
Bracci, Paige M.
Brinton, Louise
Brooks-Wilson, Angela R.
Bueno-de-Mesquita, H. Bas
Burdett, Laurie
Buring, Julie
Butler, Mary Ann
Cai, Qiuyin
Cancel-Tassin, Geraldine
Canzian, Federico
Carrato, Alfredo
Carreon, Tania
Carta, Angela
Chan, John K. C.
Chang, Ellen T.
Chang, Gee-Chen
Chang, I-Shou
Chang, Jiang
Chang-Claude, Jenny
Chen, Chien-Jen
Chen, Chih-Yi
Chen, Chu
Chen, Chung-Hsing
Chen, Constance
Chen, Hongyan
Chen, Kexin
Chen, Kuan-Yu
Chen, Kun-Chieh
Chen, Ying
Chen, Ying-Hsiang
Chen, Yi-Song
Chen, Yuh-Min
Chien, Li-Hsin
Chirlaque, Maria-Dolores
Choi, Jin Eun
Choi, Yi Young
Chow, Wong-Ho
Chung, Charles C.
Clavel, Jacqueline
Clavel-Chapelon, Franoise
Cocco, Pierluigi
Colt, Joanne S.
Comperat, Eva
Conde, Lucia
Connors, Joseph M.
Conti, David
Cortessis, Victoria K.
Cotterchio, Michelle
Cozen, Wendy
Crouch, Simon
Crous-Bou, Marta
Cussenot, Olivier
Davis, Faith G.
Ding, Ti
Diver, W. Ryan
Dorronsoro, Miren
Dossus, Laure
Duell, Eric J.
Ennas, Maria Grazia
Erickson, Ralph L.
Feychting, Maria
Flanagan, Adrienne M.
Foretova, Lenka
Fraumeni, Joseph F., Jr.
Freedman, Neal D.
Freeman, Laura E. Beane
Fuchs, Charles
Gago-Dominguez, Manuela
Gallinger, Steven
Gao, Yu-Tang
Gapstur, Susan M.
Garcia-Closas, Montserrat
Garcia-Closas, Reina
Gascoyne, Randy D.
Gastier-Foster, Julie
Gaudet, Mia M.
Gaziano, J. Michael
Giffen, Carol
Giles, Graham G.
Giovannucci, Edward
Glimelius, Bengt
Goggins, Michael
Gokgoz, Nalan
Goldstein, Alisa M.
Gorlick, Richard
Gross, Myron
Grubb, Robert, III
Gu, Jian
Guan, Peng
Gunter, Marc
Guo, Huan
Habermann, Thomas M.
Haiman, Christopher A.
Halai, Dina
Hallmans, Goran
Hassan, Manal
Hattinger, Claudia
He, Qincheng
He, Xingzhou
Helzlsouer, Kathy
Henderson, Brian
Henriksson, Roger
Hjalgrim, Henrik
Hoffman-Bolton, Judith
Hohensee, Chancellor
Holford, Theodore R.
Holly, Elizabeth A.
Hong, Yun-Chul
Hoover, Robert N.
Horn-Ross, Pamela L.
Hosain, G. M. Monawar
Hosgood, H. Dean, III
Hsiao, Chin-Fu
Hu, Nan
Hu, Wei
Hu, Zhibin
Huang, Ming-Shyan
Huerta, Jose-Maria
Hung, Jen-Yu
Hutchinson, Amy
Inskip, Peter D.
Jackson, Rebecca D.
Jacobs, Eric J.
Jenab, Mazda
Jeon, Hyo-Sung
Ji, Bu-Tian
Jin, Guangfu
Jin, Li
Johansen, Christoffer
Johnson, Alison
Jung, Yoo Jin
Kaaks, Rudolph
Kamineni, Aruna
Kane, Eleanor
Kang, Chang Hyun
Karagas, Margaret R.
Kelly, Rachel S.
Khaw, Kay-Tee
Kim, Christopher
Kim, Hee Nam
Kim, Jin Hee
Kim, Jun Suk
Kim, Yeul Hong
Kim, Young Tae
Kim, Young-Chul
Kitahara, Cari M.
Klein, Alison P.
Klein, Robert J.
Kogevinas, Manolis
Kohno, Takashi
Kolonel, Laurence N.
Kooperberg, Charles
Kricker, Anne
Krogh, Vittorio
Kunitoh, Hideo
Kurtz, Robert C.
Kweon, Sun-Seog
LaCroix, Andrea
Lawrence, Charles
Lecanda, Fernando
Lee, Victor Ho Fun
Li, Donghui
Li, Haixin
Li, Jihua
Li, Yao-Jen
Li, Yuqing
Liao, Linda M.
Liebow, Mark
Lightfoot, Tracy
Lim, Wei-Yen
Lin, Chien-Chung
Lin, Dongxin
Lindstrom, Sara
Linet, Martha S.
Link, Brian K.
Liu, Chenwei
Liu, Jianjun
Liu, Li
Ljungberg, Boerje
Lloreta, Josep
Di Lollo, Simonetta
Lu, Daru
Lund, Eiluv
Malats, Nuria
Mannisto, Satu
Le Marchand, Loic
Marina, Neyssa
Masala, Giovanna
Mastrangelo, Giuseppe
Matsuo, Keitaro
Maynadie, Marc
Mckay, James
McKean-Cowdin, Roberta
Melbye, Mads
Melin, Beatrice S.
Michaud, Dominique S.
Mitsudomi, Tetsuya
Monnereau, Alain
Montalvan, Rebecca
Moore, Lee E.
Mortensen, Lotte Maxild
Nieters, Alexandra
North, Kari E.
Novak, Anne J.
Oberg, Ann L.
Offit, Kenneth
Oh, In-Jae
Olson, Sara H.
Palli, Domenico
Pao, William
Park, In Kyu
Park, Jae Yong
Park, Kyong Hwa
Patino-Garcia, Ana
Pavanello, Sofia
Peeters, Petra H. M.
Perng, Reury-Perng
Peters, Ulrike
Petersen, Gloria M.
Picci, Piero
Pike, Malcolm C.
Porru, Stefano
Prescott, Jennifer
Prokunina-Olsson, Ludmila
Qian, Biyun
Qiao, You-Lin
Rais, Marco
Riboli, Elio
Riby, Jacques
Risch, Harvey A.
Rizzato, Cosmeri
Rodabough, Rebecca
Roman, Eve
Roupret, Morgan
Ruder, Avima M.
de Sanjose, Silvia
Scelo, Ghislaine
Schned, Alan
Schumacher, Fredrick
Schwartz, Kendra
Schwenn, Molly
Scotlandi, Katia
Seow, Adeline
Serra, Consol
Serra, Massimo
Sesso, Howard D.
Setiawan, Veronica Wendy
Severi, Gianluca
Severson, Richard K.
Shanafelt, Tait D.
Shen, Hongbing
Shen, Wei
Shin, Min-Ho
Shiraishi, Kouya
Shu, Xiao-Ou
Siddiq, Afshan
Sierrasesumaga, Luis
Sihoe, Alan Dart Loon
Skibola, Christine F.
Smith, Alex
Smith, Martyn T.
Southey, Melissa C.
Spinelli, John J.
Staines, Anthony
Stampfer, Meir
Stern, Marianna C.
Stevens, Victoria L.
Stolzenberg-Solomon, Rachael S.
Su, Jian
Su, Wu-Chou
Sund, Malin
Sung, Jae Sook
Sung, Sook Whan
Tan, Wen
Tang, Wei
Tardon, Adonina
Thomas, David
Thompson, Carrie A.
Tinker, Lesley F.
Tirabosco, Roberto
Tjonneland, Anne
Travis, Ruth C.
Trichopoulos, Dimitrios
Tsai, Fang-Yu
Tsai, Ying-Huang
Tucker, Margaret
Turner, Jenny
Vajdic, Claire M.
Vermeulen, Roel C. H.
Villano, Danylo J.
Vineis, Paolo
Virtamo, Jarmo
Visvanathan, Kala
Wactawski-Wende, Jean
Wang, Chaoyu
Wang, Chih-Liang
Wang, Jiu-Cun
Wang, Junwen
Wei, Fusheng
Weiderpass, Elisabete
Weiner, George J.
Weinstein, Stephanie
Wentzensen, Nicolas
White, Emily
Witzig, Thomas E.
Wolpin, Brian M.
Wong, Maria Pik
Wu, Chen
Wu, Guoping
Wu, Junjie
Wu, Tangchun
Wu, Wei
Wu, Xifeng
Wu, Yi-Long
Wunder, Jay S.
Xiang, Yong-Bing
Xu, Jun
Xu, Ping
Yang, Pan-Chyr
Yang, Tsung-Ying
Ye, Yuanqing
Yin, Zhihua
Yokota, Jun
Yoon, Ho-Il
Yu, Chong-Jen
Yu, Herbert
Yu, Kai
Yuan, Jian-Min
Zelenetz, Andrew
Zeleniuch-Jacquotte, Anne
Zhang, Xu-Chao
Zhang, Yawei
Zhao, Xueying
Zhao, Zhenhong
Zheng, Hong
Zheng, Tongzhang
Zheng, Wei
Zhou, Baosen
Zhu, Meng
Zucca, Mariagrazia
Boca, Simina M.
Cerhan, James R.
Ferri, Giovanni M.
Hartge, Patricia
Hsiung, Chao Agnes
Magnani, Corrado
Miligi, Lucia
Morton, Lindsay M.
Smedby, Karin E.
Teras, Lauren R.
Vijai, Joseph
Wang, Sophia S.
Brennan, Paul
Caporaso, Neil E.
Hunter, David J.
Kraft, Peter
Rothman, Nathaniel
Silverman, Debra T.
Slager, Susan L.
Chanock, Stephen J.
Chatterjee, Nilanjan
TI Analysis of Heritability and Shared Heritability Based on Genome-Wide
Association Studies for 13 Cancer Types
SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Article
ID MULTIPLE SUSCEPTIBILITY LOCI; LUNG-CANCER; FAMILIAL RISK;
PANCREATIC-CANCER; SWEDEN; INDIVIDUALS; MUTATIONS; RELATIVES; LYMPHOMA;
DATABASE
AB Background: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites.
Methods: Between 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association studies (GWAS) for 49 492 cancer case patients and 34 131 control patients. We apply novel mixed model methodology (GCTA) to this GWAS data to estimate the heritability of individual cancers, as well as the proportion of heritability attributable to cigarette smoking in smoking-related cancers, and the genetic correlation between pairs of cancers.
Results: GWAS heritability was statistically significant at nearly all sites, with the estimates of array-based heritability, h(l)(2), on the liability threshold (LT) scale ranging from 0.05 to 0.38. Estimating the combined heritability of multiple smoking characteristics, we calculate that at least 24% (95% confidence interval [CI] = 14% to 37%) and 7% (95% CI = 4% to 11%) of the heritability for lung and bladder cancer, respectively, can be attributed to genetic determinants of smoking. Most pairs of cancers studied did not show evidence of strong genetic correlation. We found only four pairs of cancers with marginally statistically significant correlations, specifically kidney and testes (rho = 0.73, SE = 0.28), diffuse large B-cell lymphoma (DLBCL) and pediatric osteosarcoma (rho = 0.53, SE = 0.21), DLBCL and chronic lymphocytic leukemia (CLL) (rho = 0.51, SE = 0.18), and bladder and lung (rho = 0.35, SE = 0.14). Correlation analysis also indicates that the genetic architecture of lung cancer differs between a smoking population of European ancestry and a nonsmoking Asian population, allowing for the possibility that the genetic etiology for the same disease can vary by population and environmental exposures.
Conclusion: Our results provide important insights into the genetic architecture of cancers and suggest new avenues for investigation.
C1 [Sampson, Joshua N.; Panagiotou, Orestis; Berndt, Sonja I.; Lan, Qing; Abnet, Christian C.; Amundadottir, Laufey T.; Mirabello, Lisa; Savage, Sharon A.; Taylor, Philip R.; McGlynn, Katherine A.; Rajaraman, Preetha; Albanes, Demetrius; Bassig, Bryan A.; Black, Amanda; Brinton, Louise; Chow, Wong-Ho; Chung, Charles C.; Colt, Joanne S.; Fraumeni, Joseph F., Jr.; Freedman, Neal D.; Freeman, Laura E. Beane; Garcia-Closas, Montserrat; Goldstein, Alisa M.; Hoover, Robert N.; Hu, Nan; Hu, Wei; Inskip, Peter D.; Ji, Bu-Tian; Kitahara, Cari M.; Liao, Linda M.; Linet, Martha S.; Moore, Lee E.; Prokunina-Olsson, Ludmila; Stolzenberg-Solomon, Rachael S.; Tang, Wei; Tucker, Margaret; Wang, Chaoyu; Weinstein, Stephanie; Wentzensen, Nicolas; Yu, Kai; Hartge, Patricia; Caporaso, Neil E.; Rothman, Nathaniel; Silverman, Debra T.; Chanock, Stephen J.; Chatterjee, Nilanjan] NCI, Div Canc Epidemiol & Genet, Bethesda, MD USA.
[Wheeler, William A.; Giffen, Carol] Informat Management Serv Inc, Silver Spring, MD USA.
[Yeager, Meredith; Wang, Zhaoming; Burdett, Laurie; Hutchinson, Amy; Liu, Chenwei] Natl Canc Inst, Div Canc Epidemiol & Genet, Canc Genom Res Lab, Gaithersburg, MD USA.
[De Vivo, Immaculata; Bertrand, Kimberly A.; Birmann, Brenda M.; Chen, Constance; Crous-Bou, Marta; Fuchs, Charles; Giovannucci, Edward; Lindstrom, Sara; Prescott, Jennifer; Stampfer, Meir; Hunter, David J.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA.
[De Vivo, Immaculata; Bertrand, Kimberly A.; Birmann, Brenda M.; Chen, Constance; Crous-Bou, Marta; Fuchs, Charles; Giovannucci, Edward; Lindstrom, Sara; Prescott, Jennifer; Stampfer, Meir; Hunter, David J.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[De Vivo, Immaculata; Bertrand, Kimberly A.; Chen, Constance; Crous-Bou, Marta; Giovannucci, Edward; Kelly, Rachel S.; Lindstrom, Sara; Prescott, Jennifer; Sesso, Howard D.; Stampfer, Meir; Trichopoulos, Dimitrios; Hunter, David J.; Kraft, Peter] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Purdue, Mark P.] Ontario Hlth Study, Toronto, ON, Canada.
[Adami, Hans-Olov; Weiderpass, Elisabete] Karolinska Inst, Dept Med Epidemiol & Biostatist, Stockholm, Sweden.
[Ahlbom, Anders; Feychting, Maria] Karolinska Inst, Inst Environm Med, Dept Epidemiol, S-10401 Stockholm, Sweden.
[Amary, Maria Fernanda; Flanagan, Adrienne M.; Halai, Dina] UCL Canc Inst, London, England.
[Amary, Maria Fernanda; Flanagan, Adrienne M.; Halai, Dina; Tirabosco, Roberto] Royal Natl Orthopaed Hosp NHS Trust, Middlesbrough, Cleveland, England.
[An, She-Juan; Su, Jian; Wu, Yi-Long; Zhang, Xu-Chao] Guangdong Acad Med Sci, Guangdong Gen Hosp, Guangdong Prov Key Lab Translat Med Lung Canc, Guangdong Lung Canc Inst, Guangzhou, Guangdong, Peoples R China.
[Andersson, Ulrika; Henriksson, Roger; Melin, Beatrice S.] Umea Univ, Dept Radiat Sci Oncol, Umea, Sweden.
[Andriole, Gerald, Jr.; Grubb, Robert, III] Washington Univ, Sch Med, Div Urol Surg, St Louis, MO 63110 USA.
[Andrulis, Irene L.; Gokgoz, Nalan; Wunder, Jay S.] Univ Toronto, Litwin Ctr Canc Genet, Toronto, ON, Canada.
[Andrulis, Irene L.; Gallinger, Steven; Gokgoz, Nalan; Wunder, Jay S.] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Toronto, ON M5G 1X5, Canada.
[Angelucci, Emanuele] Osped Oncol Riferimento Regionale Businco, Hematol Unit, Cagliari, Italy.
[Ansell, Stephen M.; Habermann, Thomas M.; Liebow, Mark; Novak, Anne J.; Shanafelt, Tait D.; Thompson, Carrie A.; Witzig, Thomas E.] Mayo Clin, Dept Med, Rochester, MN USA.
[Arici, Cecilia; Carta, Angela; Porru, Stefano] Univ Brescia, Dept Med & Surg Specialties, Radiol Sci & Publ Hlth, Brescia, Italy.
[Armstrong, Bruce K.; Kricker, Anne] Univ Sydney, Sydney Sch Publ Hlth, Sydney, NSW 2006, Australia.
[Arslan, Alan A.] NYU, Sch Med, Dept Obstet & Gynecol, New York, NY USA.
[Arslan, Alan A.; Zelenetz, Andrew] NYU, Sch Med, Dept Environm Med, New York, NY USA.
[Arslan, Alan A.; Zelenetz, Andrew] NYU, Sch Med, Dept Populat Hlth, New York, NY USA.
[Arslan, Alan A.; Zelenetz, Andrew] NYU Langone, Med Ctr, Perlmutter Canc Ctr, New York, NY USA.
[Austin, Melissa A.; White, Emily] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Barkauskas, Donald A.; Van Den Berg, David; Conti, David; Cortessis, Victoria K.; Cozen, Wendy; Henderson, Brian; McKean-Cowdin, Roberta; Schumacher, Fredrick; Setiawan, Veronica Wendy] Univ So Calif, Dept Prevent Med, USC Keck Sch Med, Los Angeles, CA 90089 USA.
[Bassig, Bryan A.; Zhang, Yawei; Zheng, Tongzhang] Yale Sch Publ Hlth, Dept Environm Hlth Sci, New Haven, CT USA.
German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Baden Wurttembe, Germany.
[Benavente, Yolanda; de Sanjose, Silvia] Inst Catala Oncol, IDIBELL, Unit Infect & Canc UNIC, Canc Epidemiol Res Programme, Barcelona, Spain.
[Benavente, Yolanda; Chirlaque, Maria-Dolores; Dorronsoro, Miren; Lloreta, Josep; Tardon, Adonina] Ctr Invest Biomed Red Epidemiol Salud Publ CIBERE, Madrid, Spain.
[Benhamou, Simone] Fdn Jean Dausset Ctr Etude Polymorphisme Humain C, Inst Natl sante & Rech med, U946, Paris, France.
[Benhamou, Simone] Ctr Natl Receherche Sci, Inst Gustave Roussy, UMR8200, Villejuif, France.
[Berg, Christine] Natl Canc Inst, Canc Prevent Div, Early Detect Res Grp, Bethesda, MD USA.
[Van Den Berg, David; Conti, David; Cortessis, Victoria K.; Cozen, Wendy] Univ So Calif, Norris Comprehens Canc Ctr, USC Keck Sch Med, Los Angeles, CA USA.
[Bernstein, Leslie; Wang, Sophia S.] Beckman Res Inst City Hope, Dept Canc Etiol, Duarte, CA USA.
[Boeing, Heiner] German Inst Human Nutr, Dept Epidemiol, Potsdam, Germany.
[Boffetta, Paolo] Tisch Canc Inst, Icahn Sch Med Mt Sinai, New York, NY USA.
[Clavel-Chapelon, Franoise; Dossus, Laure] Ctr Res Epidemiol & Populat Hlth CESP, INSERM, Nutr,Hormones & Womens Hlth team, U1018, F-94805 Villejuif, France.
[Boutron-Ruault, Marie-Christine; Clavel, Jacqueline; Clavel-Chapelon, Franoise; Dossus, Laure; Monnereau, Alain] Univ Paris 11, F-94805 Villejuif, France.
[Boutron-Ruault, Marie-Christine; Clavel-Chapelon, Franoise; Dossus, Laure] Inst Gustave Roussy, F-94805 Villejuif, France.
[Bracci, Paige M.; Holly, Elizabeth A.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
[Brooks-Wilson, Angela R.] BC Canc Agcy, Genome Sci Ctr, Vancouver, BC, Canada.
[Brooks-Wilson, Angela R.] Simon Fraser Univ, Dept Biomed Physiol & Kinesiol, Burnaby, BC V5A 1S6, Canada.
[Bueno-de-Mesquita, H. Bas] Natl Inst Publ Hlth & Environm RIVM, Bilthoven, Netherlands.
[Bueno-de-Mesquita, H. Bas] Univ Med Ctr Utrecht, Dept Gastroenterol & Hepatol, Utrecht, Netherlands.
[Buring, Julie; Gaziano, J. Michael; Sesso, Howard D.] Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02115 USA.
[Buring, Julie; Gaziano, J. Michael; Sesso, Howard D.] Harvard Univ, Sch Med, Boston, MA USA.
[Buring, Julie; Gaziano, J. Michael; Sesso, Howard D.] Brigham & Womens Hosp, Dept Med, Div Aging, Boston, MD 02115 USA.
[Buring, Julie; Gaziano, J. Michael; Sesso, Howard D.] Harvard Univ, Sch Med, Boston, MD USA.
[Butler, Mary Ann; Carreon, Tania; Ruder, Avima M.] NIOSH, Ctr Dis Control & Prevent, Cincinnati, OH 45226 USA.
[Cai, Qiuyin; Shu, Xiao-Ou; Zheng, Wei] Vanderbilt Univ, Ctr Med, Dept Med, Nashville, TN 37232 USA.
[Cai, Qiuyin; Shu, Xiao-Ou; Zheng, Wei] Vanderbilt Univ, Med Ctr, Vanderbilt Ingram Canc Ctr, Nashville, TN USA.
[Cancel-Tassin, Geraldine; Comperat, Eva; Cussenot, Olivier; Roupret, Morgan] Ctr Rech Pathol Prostat, Paris, France.
[Cancel-Tassin, Geraldine; Comperat, Eva; Cussenot, Olivier; Roupret, Morgan] Univ Paris 06, ONCOTYPE URO, GRC 5, Paris, France.
[Canzian, Federico; Rizzato, Cosmeri] German Canc Res Ctr, Genom Epidemiol Grp, Heidelberg, Germany.
[Carrato, Alfredo] Ramon y Cajal Univ Hosp, Madrid, Spain.
[Chan, John K. C.] Queen Elizabeth Hosp, Dept Pathol, Hong Kong, Hong Kong, Peoples R China.
[Chang, Ellen T.] Stanford Univ, Sch Med, Div Epidemiol, Dept Hlth Res & Policy, Stanford, CA 94305 USA.
[Chang, Ellen T.] Exponent Inc, Ctr Epidemiol & Computat Biol, Hlth Sci, Menlo Pk, CA USA.
[Chang, Gee-Chen] Natl Yang Ming Univ, Sch Med, Dept Med, Taipei 112, Taiwan.
[Chang, Gee-Chen; Chen, Kun-Chieh; Yang, Tsung-Ying] Taichung Vet Gen Hosp, Div Chest Med, Dept Internal Med, Taichung, Taiwan.
[Chang, I-Shou; Chen, Chung-Hsing; Tsai, Fang-Yu] Natl Hlth Res Inst, Natl Inst Canc Res, Zhunan, Taiwan.
[Chang, Jiang; Lin, Dongxin; Tan, Wen; Wu, Chen] Chinese Acad Med Sci, Canc Inst & Hosp, Dept Etiol & Carcinogenesis, Beijing 100730, Peoples R China.
[Chang, Jiang; Lin, Dongxin; Tan, Wen; Wu, Chen] Peking Union Med Coll, Beijing 100021, Peoples R China.
[Chen, Chien-Jen; Li, Yao-Jen] Genom Res Ctr, Taipei, Taiwan.
[Chen, Chih-Yi] Chung Shan Med Univ, Chung Shan Med Univ Hosp, Dept Surg, Div Thorac Surg,Inst Med, Taichung, Taiwan.
[Chen, Chu; Hohensee, Chancellor] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA.
[Chen, Chu; Giovannucci, Edward; Stampfer, Meir; Hunter, David J.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Chen, Hongyan; Jin, Li; Lu, Daru; Wang, Jiu-Cun; Wu, Junjie; Zhao, Xueying; Zhao, Zhenhong] Fudan Univ, Sch Life Sci, Minist Educ, Key Lab Contemporary Anthropol, Shanghai 200433, Peoples R China.
[Chen, Kexin; Li, Haixin; Zheng, Hong] Med Univ, Canc Inst & Hosp, Natl Clin Res Ctr Canc, Key Lab Canc Prevent & Therapy,Dept Epidemiol & B, Tianjin, Peoples R China.
[Chen, Kuan-Yu; Yu, Chong-Jen] Natl Taiwan Univ Hosp, Dept Internal Med, Taipei 100, Taiwan.
[Chen, Ying; Lim, Wei-Yen; Seow, Adeline] Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore 117548, Singapore.
[Chen, Ying-Hsiang; Chen, Yi-Song; Chien, Li-Hsin; Hsiao, Chin-Fu] Natl Hlth Res Inst, Inst Populat Hlth Sci, Zhunan, Taiwan.
[Chen, Yuh-Min; Perng, Reury-Perng] Taipei Vet Gen Hosp, Dept Chest Med, Taipei, Taiwan.
[Chen, Yuh-Min] Taipei Med Univ, Taipei Canc Ctr, Taipei, Taiwan.
[Chirlaque, Maria-Dolores; Huerta, Jose-Maria] IMIB Arrixaca, Dept Epidemiol, Murcia Reg Hlth Author, Murcia, Spain.
[Choi, Jin Eun; Choi, Yi Young] Kyungpook Natl Univ, Med Ctr, Canc Res Ctr, Daegu, South Korea.
[Clavel, Jacqueline; Monnereau, Alain] INSERM, Ctr Res Epidemiol & Populat Hlth CESP, U1018, Environm Epidemiol Canc Grp, Villejuif, France.
[Cocco, Pierluigi; Rais, Marco] Univ Cagliari, Dept Publ Hlth Clin & Mol Med, Cagliari, Italy.
[Comperat, Eva; Roupret, Morgan] AP HP, Pitie Salpetriere, Dept Urol, Paris, France.
[Comperat, Eva] AP HP, Pitie Salpetriere, Dept Pathol, Paris, France.
[Conde, Lucia; Riby, Jacques; Skibola, Christine F.] Univ Alabama Birmingham, Sch Publ Hlth, Dept Epidemiol, Birmingham, AL 35294 USA.
[Conde, Lucia; Riby, Jacques; Skibola, Christine F.] Univ Alabama Birmingham, Ctr Comprehens Canc, Birmingham, AL 35294 USA.
[Conde, Lucia; Riby, Jacques; Skibola, Christine F.; Smith, Martyn T.] Univ Calif Berkeley, Sch Publ Hlth, Div Environm Hlth Sci, Berkeley, CA 94720 USA.
[Conde, Lucia; Riby, Jacques; Skibola, Christine F.; Smith, Martyn T.] BC Canc Agcy, Ctr Lymphoid Canc, Vancouver, BC, Canada.
[Connors, Joseph M.] Univ British Columbia, Dept Med, Vancouver, BC, Canada.
[Cortessis, Victoria K.] Univ So Calif, Dept Obstet & Gynecol, Los Angeles, CA 90089 USA.
[Cotterchio, Michelle] Canc Care Ontario, Toronto, ON, Canada.
[Cotterchio, Michelle] Univ Toronto, Dalla Lana Sch Publ Hlth, Toronto, ON, Canada.
[Crouch, Simon; Kane, Eleanor; Lightfoot, Tracy; Riboli, Elio; Smith, Alex] Univ York, Dept Hlth Sci, York YO10 5DD, N Yorkshire, England.
[Cussenot, Olivier] Hop Tenon, AP HP, Dept Urol, F-75970 Paris, France.
[Davis, Faith G.] Univ Alberta, Sch Publ Hlth, Edmonton, AB, Canada.
[Ding, Ti] Shanxi Canc Hosp, Taiyuan, Shanxi, Peoples R China.
[Diver, W. Ryan; Gapstur, Susan M.; Gaudet, Mia M.; Jacobs, Eric J.; Stevens, Victoria L.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA.
[Dorronsoro, Miren] BioDonostia Res Inst, Dept Hlth, Basque Region, Spain.
[Duell, Eric J.] Bellvitge Biomed Res Inst IDIBELL, Catalan Inst Oncol ICO, Canc Epidemiol Res Program, Unit Nutr Environm & Canc, Barcelona, Spain.
[Ennas, Maria Grazia] Univ Cagliari, Dept Biomed Sci, Cagliari, Italy.
[Erickson, Ralph L.] Walter Reed Army Inst Res, Silver Spring, MD USA.
[Foretova, Lenka] Masaryk Mem Canc Inst, Dept Canc Epidemiol & Genet, Brno, Czech Republic.
[Foretova, Lenka] MF MU, Brno, Czech Republic.
[Fuchs, Charles; Wolpin, Brian M.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Gago-Dominguez, Manuela] Inst Invest Sanitaria de Santiago, Serv Galego Saude SERGAS, Galician Fdn Genom Med, Genom Med Grp, Santiago De Compostela, Spain.
[Gao, Yu-Tang] Shanghai Canc Inst, Dept Epidemiol, Shanghai, Peoples R China.
[Garcia-Closas, Montserrat] Inst Canc Res, Div Genet & Epidemiol, London, England.
[Garcia-Closas, Reina] Hosp Univ Canarias, Unidad Invest, San Cristobal la Laguna, Spain.
[Gascoyne, Randy D.] Univ British Columbia, Dept Pathol, Vancouver, BC, Canada.
[Gastier-Foster, Julie] Nationwide Childrens Hosp, Columbus, OH USA.
[Gastier-Foster, Julie] Ohio State Univ, Dept Pathol & Pediat, Columbus, OH 43210 USA.
[Gaziano, J. Michael] Vet Affairs Boston Healthcare Syst, Geriatr Res Educ & Clin Ctr, Massachusetts Vet Epidemiol Res & Informat Ctr, Boston, MA USA.
[Giles, Graham G.; Severi, Gianluca] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic, Australia.
[Giles, Graham G.; Severi, Gianluca] Univ Melbourne, Melbourne Sch Populat & Global Hlth, Ctr Biostat & Epidemiol, Carlton, Vic 3053, Australia.
[Glimelius, Bengt] Karolinska Inst, Dept Pathol & Oncol, Stockholm, Sweden.
[Glimelius, Bengt] Uppsala Univ, Dept Radiol Oncol & Radiat Sci, Uppsala, Sweden.
[Goggins, Michael] Sidney Kimmel Canc Ctr, Dept Oncol, Baltimore, MD USA.
[Goggins, Michael] Johns Hopkins Univ, Baltimore, MD USA.
[Goggins, Michael] Sidney Kimmel Canc Ctr, Dept Pathol, Baltimore, MD USA.
[Goggins, Michael] Sidney Kimmel Canc Ctr, Dept Med, Baltimore, MD USA.
[Gorlick, Richard] Childrens Hosp Montefiore, Albert Einstein Coll Med, Bronx, NY USA.
[Gross, Myron] Univ Minnesota, Lab Med & Pathol, Minneapolis, MN USA.
[Gu, Jian; Wu, Xifeng; Ye, Yuanqing] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA.
[Guan, Peng; He, Qincheng; Wactawski-Wende, Jean; Yin, Zhihua; Zhou, Baosen] China Med Univ, Sch Publ Hlth, Dept Epidemiol, Shenyang 110001, Peoples R China.
[Gunter, Marc; Peeters, Petra H. M.] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England.
[Guo, Huan; Wu, Tangchun] Huazhong Univ Sci & Technol, Sch Publ Hlth, Inst Occupat Med, Wuhan 430074, Peoples R China.
[Guo, Huan; Wu, Tangchun] Huazhong Univ Sci & Technol, Sch Publ Hlth, Minist Educ, Key Lab Environm & Hlth, Wuhan 430074, Peoples R China.
[Hallmans, Goran] Umea Univ, Dept Publ Hlth & Clin Med, Nutr Res, Umea, Sweden.
[Hassan, Manal; Li, Donghui] Univ Texas MD Anderson Canc Ctr, Dept Gastrointestinal Med Oncol, Houston, TX USA.
[Picci, Piero; Schwartz, Kendra; Serra, Massimo] Orthopaed Rizzoli Inst, Expt Oncol Lab, Bologna, Italy.
[He, Xingzhou] Chinese Ctr Dis Control & Prevent, Beijing, Peoples R China.
[Helzlsouer, Kathy; Hoffman-Bolton, Judith; Klein, Alison P.; Visvanathan, Kala] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Hjalgrim, Henrik; Melbye, Mads] Statens Serum Inst, Dept Epidemiol Res, Div Hlth Surveillance & Res, DK-2300 Copenhagen, Denmark.
[Holford, Theodore R.] Yale Univ, Sch Publ Hlth, Dept Biostat, New Haven, CT USA.
[Hong, Yun-Chul] Seoul Natl Univ, Coll Med, Dept Prevent Med, Seoul, South Korea.
[Horn-Ross, Pamela L.] Canc Prevent Inst Calif, Fremont, CA USA.
[Hosain, G. M. Monawar] New Hampshire State Canc Registry, Concord, NH USA.
[Hosgood, H. Dean, III] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA.
[Hsiao, Chin-Fu] Natl Hlth Res Inst, Taiwan Lung Canc Tissue Specimen Informat Resourc, Zhunan, Taiwan.
[Hu, Zhibin; Jin, Guangfu; Shen, Hongbing; Shen, Wei] Nanjing Med Univ, Jiangsu Collaborat Innovat Ctr Canc Personalized, Nanjing, Jiangsu, Peoples R China.
[Hu, Zhibin; Jin, Guangfu; Shen, Hongbing; Shen, Wei] Nanjing Med Univ, Sch Publ Hlth, Ctr Canc, Jiangsu Key Lab Canc Biomarkers Prevent & Treatme, Nanjing, Jiangsu, Peoples R China.
[Huang, Ming-Shyan; Hung, Jen-Yu] Kaohsiung Med Univ, Sch Med, Kaohsiung Med Univ Hosp, Dept Internal Med, Kaohsiung, Taiwan.
[Jackson, Rebecca D.] Ohio State Univ, Div Endocrinol Diabet & Metab, Columbus, OH 43210 USA.
[Jenab, Mazda; Mckay, James; Scelo, Ghislaine; Brennan, Paul] Int Agcy Res Canc, F-69372 Lyon, France.
[Jeon, Hyo-Sung] Kyungpook Natl Univ, Mol Diagnost & Imaging Ctr, Daegu, South Korea.
[Johansen, Christoffer] Danish Canc Soc Res Ctr, Unit Survivorship, Copenhagen, Denmark.
[Johnson, Alison] Vermont Canc Registry, Burlington, VT USA.
[Jung, Yoo Jin; Kang, Chang Hyun; Kim, Young Tae; Park, In Kyu] Seoul Natl Univ, Coll Med, Canc Res Inst, Dept Thorac & Cardiovasc Surg, Seoul, South Korea.
[Kamineni, Aruna] Grp Hlth Res Inst, Seattle, WA USA.
[Karagas, Margaret R.; Schned, Alan] Dartmouth Coll, Geisel Sch Med, Hanover, NH 03755 USA.
[Kelly, Rachel S.; Vineis, Paolo] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, MRC PHE Ctr Environm & Hlth, London, England.
[Khaw, Kay-Tee] Univ Cambridge, Cambridge CB2 1TN, England.
[Kim, Hee Nam] Chonnam Natl Univ, Ctr Creat Biomed Scientists, Gwangju, South Korea.
[Kim, Jin Hee] Seoul Natl Univ, Grad Sch Publ Hlth, Dept Environm Hlth, Seoul, South Korea.
[Kim, Jun Suk] Korea Univ, Guro Hosp, Coll Med, Dept Internal Med,Div Med Oncol, Seoul, South Korea.
[Kim, Yeul Hong; Park, Kyong Hwa] Korea Univ, Coll Med, Anam Hosp, Div Hematol Oncol,Dept Internal Med, Seoul 136705, South Korea.
[Kim, Young-Chul; Oh, In-Jae] Chonnam Natl Univ, Hwasun Hosp, Lung & Esophageal Canc Clin, Hwasun Eup, South Korea.
[Kim, Young-Chul; Oh, In-Jae] Chonnam Natl Univ, Sch Med, Dept Internal Med, Gwangju, South Korea.
[Klein, Alison P.] Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA.
[Klein, Robert J.] Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, Icahn Inst Genom & Multiscale Biol, New York, NY 10029 USA.
[Kogevinas, Manolis] Ctr Res Environm Epidemiol CREAL, Barcelona, Spain.
[Kogevinas, Manolis] Hosp del Mar, Municipal Inst Med Res IMIM, Barcelona, Spain.
[Kogevinas, Manolis] Natl Sch Publ Hlth, Athens, Greece.
[Kohno, Takashi] Natl Canc Ctr, Res Inst, Div Genome Biol, Tokyo 104, Japan.
[Kolonel, Laurence N.] Canc Res Ctr Hawaii, Honolulu, HI USA.
[Krogh, Vittorio] Fdn IRCCS Ist Nazl Tumori, Epidemiol & Prevent Unit, Milan, Italy.
[Kunitoh, Hideo] Japanese Red Cross Med Ctr, Dept Med Oncol, Tokyo, Japan.
[Kurtz, Robert C.; Offit, Kenneth; Villano, Danylo J.; Virtamo, Jarmo; Zelenetz, Andrew] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA.
[Kweon, Sun-Seog] Chonnam Natl Univ, Hwasun Hosp, Jeonnam Reg Canc Ctr, Hwasun Eup, South Korea.
[Kweon, Sun-Seog; Shin, Min-Ho] Chonnam Natl Univ, Sch Med, Dept Prevent Med, Gwangju, South Korea.
[Lawrence, Charles; Montalvan, Rebecca] Westat Corp, Rockville, MD USA.
[Lecanda, Fernando; Patino-Garcia, Ana; Sierrasesumaga, Luis] Univ Navarra, Univ Navarra Clin, Dept Pediat, Pamplona, Spain.
[Lee, Victor Ho Fun] Univ Hong Kong, Dept Clin Oncol, Hong Kong, Hong Kong, Peoples R China.
[Liu, Jianjun] Qujing Ctr Dis Control & Prevent, Sanjiangdadao, Qujing, Peoples R China.
[Li, Yuqing] Canc Prevent Inst Calif, Fremont, CA USA.
[Lin, Chien-Chung] Natl Cheng Kung Univ, Cheng Kung Univ Med Coll & Hosp, Dept Internal Med, Tainan 701, Taiwan.
[Weiner, George J.] Univ Iowa, Carver Coll Med, Dept Internal Med, Iowa City, IA USA.
[Liu, Jianjun] Genome Inst Singapore, Human Genet, Singapore, Singapore.
[Liu, Li] Huazhong Univ Sci & Technol, Ctr Canc, Union Hosp, Wuhan 430074, Peoples R China.
Umea Univ, Dept Surg & Perioperat Sci Urol & Androl, Umea, Sweden.
Univ Florence, Dept Surg & Translat Med, Sect Anatomopathol, Florence, Italy.
[Lund, Eiluv; Weiderpass, Elisabete] Univ Tromso, Arctic Univ Norway, Fac Hlth Sci, Dept Community Med, Tromso, Norway.
Spanish Natl Canc Res Ctr CNIO, Genet & Mol Epidemiol Grp, Madrid, Spain.
[Mannisto, Satu; Virtamo, Jarmo] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland.
[Le Marchand, Loic; Yu, Herbert] Univ Hawaii, Ctr Canc, Canc Epidemiol Program, Honolulu, HI 96822 USA.
Stanford Univ, Lucile Packard Childrens Hosp, Palo Alto, CA 94304 USA.
[Masala, Giovanna; Palli, Domenico] Canc Res & Prevent Inst ISPO, Mol & Nutr Epidemiol Unit, Florence, Italy.
[Mastrangelo, Giuseppe; Pavanello, Sofia] Univ Padua, Dept Cardiac Thorac & Vasc Sci, Padua, Italy.
[Matsuo, Keitaro] Aichi Canc Res Inst, Div Mol Med, Nagoya, Aichi, Japan.
[Maynadie, Marc] Univ Burgundy, Registre Hemopathies Malignes Cote dOr, EA 4184, Dijon, France.
[Maynadie, Marc] Dijon Univ Hosp, Dijon, France.
[Melbye, Mads] Stanford Univ, Dept Med, Sch Med, Stanford, CA 94305 USA.
Brown Univ, Dept Epidemiol, Div Biol & Med, Providence, RI 02912 USA.
[Riboli, Elio; Siddiq, Afshan] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, London, England.
[Mitsudomi, Tetsuya] Kinki Univ, Sch Med, Div Thorac Surg, Sayama, Osaka 589, Japan.
[Monnereau, Alain] Inst Bergonie, Registre Hemopathies Malignes Gironde, Bordeaux, France.
Aarhus Univ, Epidemiol Sect, DK-8000 Aarhus C, Denmark.
Aalborg Univ Hosp, Dept Cardiol, Aalborg, Denmark.
[Nieters, Alexandra] Univ Med Ctr Freiburg, Ctr Chron Immunodeficiency, Freiburg, Baden Wurttembe, Germany.
[North, Kari E.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA.
[North, Kari E.] Univ N Carolina, Carolina Ctr Genome Sci, Chapel Hill, NC USA.
[Oberg, Ann L.] Mayo Clin, Dept Hlth Sci Res, Div Biomed Stat & Informat, Rochester, MN USA.
[Olson, Sara H.; Pike, Malcolm C.] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA.
[Pao, William] Vanderbilt Univ, Med Ctr, Div Hematol & Oncol, Nashville, TN 37235 USA.
[Park, Jae Yong] Kyungpook Natl Univ, Med Ctr, Lung Canc Ctr, Daegu, South Korea.
[Peeters, Petra H. M.; Vermeulen, Roel C. H.] Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care 194, Utrecht, Netherlands.
[Peeters, Petra H. M.] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Primary Care & Publ Hlth, London, England.
[Petersen, Gloria M.] Mayo Clin, Div Epidemiol, Dept Hlth Sci Res, Rochester, MN USA.
[Qian, Biyun] Acad Sinica, Genom Res Ctr, Taipei 115, Taiwan.
[Qiao, You-Lin] Chinese Acad Med Sci, Canc Inst & Hosp, Dept Epidemiol, Beijing 100730, Peoples R China.
[Risch, Harvey A.] Yale Univ, Sch Publ Hlth, Dept Chron Dis Epidemiol, New Haven, CT USA.
[Severson, Richard K.] Wayne State Univ, Dept Family Med & Publ Hlth Sci, Detroit, MI USA.
Karmanos Canc Inst, Detroit, MI USA.
[Schwenn, Molly] Maine Canc Registry, Augusta, ME USA.
[Serra, Consol] Univ Pompeu Fabra, Dept Ciencies Experimentals & Salut, Barcelona, Spain.
[Severi, Gianluca; Vineis, Paolo] Human Genet Fdn, Turin, Italy.
[Sihoe, Alan Dart Loon] Queen Mary Hosp, Div Cardiothorac Surg, Dept Surg, Hong Kong, Hong Kong, Peoples R China.
Univ Melbourne, Dept Pathol, Parkville, Vic 3052, Australia.
[Spinelli, John J.] BC Canc Agcy, Canc Control Res, Vancouver, BC, Canada.
[Spinelli, John J.] Univ British Columbia, Sch Populat & Publ Hlth, Vancouver, BC V5Z 1M9, Canada.
[Staines, Anthony] Dublin City Univ, Sch Nursing & Human Sci, Dublin 9, Ireland.
[Su, Wu-Chou] Natl Cheng Kung Univ, Med Coll & Hosp, Tainan 701, Taiwan.
[Sund, Malin] Umea Univ, Dept Surg & Perioperat Sci, Surg, Umea, Sweden.
[Sung, Jae Sook] Korea Univ, Canc Res Inst, Seoul, South Korea.
[Sung, Sook Whan] Seoul St Marys Hosp, Dept Thorac & Cardiovasc Surg, Seoul, South Korea.
[Tardon, Adonina] Univ Oviedo, Inst Univ Oncol, Oviedo, Spain.
[Thomas, David] St Vincents Hosp, Garvan Inst Med Res, Kinghorn Canc Ctr, Darlinghurst, NSW 2010, Australia.
[Tjonneland, Anne] Danish Canc Soc, Res Ctr, Copenhagen, Denmark.
[Travis, Ruth C.] Univ Oxford, Canc Epidemiol Unit, Oxford, England.
[Trichopoulos, Dimitrios] Acad Athens, Bur Epidemiol Res, Athens, Greece.
[Trichopoulos, Dimitrios] Hellen Hlth Fdn, Athens, Greece.
[Tsai, Ying-Huang] Chang Gung Mem Hosp, Dept Resp Thearpy, Chiayi, Taiwan.
[Turner, Jenny] Macquarie Univ, Australian Sch Adv Med, Sydney, NSW 2109, Australia.
[Turner, Jenny] Douglass Hanly Moir Pathol, Dept Histopathol, Macquarie Pk, NSW, Australia.
[Vajdic, Claire M.] Univ New S Wales, Prince Wales Clin Sch, Sydney, NSW, Australia.
[Vermeulen, Roel C. H.] Univ Utrecht, Inst Risk Assessment Sci, Utrecht, Netherlands.
[Wactawski-Wende, Jean] SUNY Buffalo, Dept Social & Prevent Med, Buffalo, NY 14260 USA.
[Wang, Chih-Liang] Chang Gung Mem Hosp, Dept Pulm & Crit Care, Taoyuan, Taiwan.
[Wang, Jiu-Cun] Fudan Univ, Sch Life Sci, State Key Lab Genet Engn, Shanghai, Peoples R China.
[Wang, Junwen] Univ Hong Kong, Li Ka Shing Fac Med, Ctr Genom Sci, Hong Kong, Peoples R China.
[Wang, Junwen] Univ Hong Kong, Li Ka Shing Fac Med, Dept Biochem, Hong Kong, Hong Kong, Peoples R China.
[Wei, Fusheng; Wu, Guoping] China Natl Environm Monitoring Ctr, Beijing, Peoples R China.
[Weiderpass, Elisabete] Canc Registry Norway, Oslo, Norway.
[Weiderpass, Elisabete] Folkhalsan Res Ctr, Dept Genet Epidemiol, Helsinki, Finland.
[Wolpin, Brian M.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
[Wolpin, Brian M.] Harvard Univ, Sch Med, Boston, MA USA.
[Wong, Maria Pik] Univ Hong Kong, Li Ka Shing Fac Med, Dept Pathol, Hong Kong, Hong Kong, Peoples R China.
[Wu, Chen] Chinese Acad Med Sci, Canc Inst & Hosp, State Key Lab Mol Oncol, Beijing 100730, Peoples R China.
[Wu, Chen] Peking Union Med Coll, Beijing 100021, Peoples R China.
[Xiang, Yong-Bing] Shanghai Jiao Tong Univ, Sch Med, Renji Hosp, Shanghai Canc Inst, Shanghai 200030, Peoples R China.
[Xu, Jun] Univ Hong Kong, Sch Publ Hlth, Hong Kong, Hong Kong, Peoples R China.
[Xu, Ping] Wuhan Iron & Steel Corp Staff Worker Hosp, Dept Oncol, Wuhan, Peoples R China.
[Yang, Pan-Chyr] Natl Taiwan Univ, Coll Med, Dept Internal Med, Taipei, Taiwan.
[Yokota, Jun] Inst Predict & Personalized Med Canc IMPPC, Barcelona, Spain.
[Yoon, Ho-Il] Seoul Natl Univ, Bundang Hosp, Dept Internal Med, Songnam, South Korea.
[Yuan, Jian-Min] Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA.
Georgetown Univ, Med Ctr, Innovat Ctr Biomed Informat, Washington, DC USA.
Georgetown Univ, Med Ctr, Dept Oncol, Washington, DC 20007 USA.
[Cerhan, James R.; Slager, Susan L.] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA.
[Ferri, Giovanni M.] Univ Bari, Interdisciplinary Dept Med, Bari, Italy.
[Magnani, Corrado] Univ Piemonte Orientale, Dept Translat Med, CPO Piemonte & Unit Med Stat & Epidemiol, Novara, Italy.
[Mirabello, Lisa] Canc Prevent & Res Inst ISPO, Environm & Occupat Epidemiol Unit, Florence, Italy.
[Smedby, Karin E.] Karolinska Univ Hosp, Karolinska Inst, Dept Med, Stockholm, Sweden.
[Hunter, David J.] Broad Inst Harvard, Cambridge, MA USA.
[Hunter, David J.] MIT, Cambridge, MA 02139 USA.
[Kraft, Peter] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
RP Sampson, JN (reprint author), NCI, Biostat Branch, Div Canc Epidemiol & Genet, 9609 Med Ctr Dr,7E594, Rockville, MD 20815 USA.
EM joshua.sampson@nih.gov; nilanjan.chatterjee@nih.gov
RI Wang, Junwen/D-3700-2011; Qiao, You-Lin/B-4139-2012; Clavel,
Jacqueline/Q-2750-2016; Hattinger, Claudia/Q-1212-2016; Beane Freeman,
Laura/C-4468-2015; Kitahara, Cari/R-8267-2016; Jung, Yoojin/G-2519-2015;
Kogevinas, Manolis/C-3918-2017; Brooks-Wilson, Angela/E-9399-2012;
Weiderpass, Elisabete/M-4029-2016; Abnet, Christian/C-4111-2015; Purdue,
Mark/C-9228-2016; Jin, Li/C-1468-2009; Savage, Sharon/B-9747-2015; de
Sanjose Llongueras, Silvia/H-6339-2014; Andrulis, Irene/E-7267-2013;
Gallinger, Steven/E-4575-2013; Benhamou, Simone/K-6554-2015; Krogh,
Vittorio/K-2628-2016
OI Wang, Junwen/0000-0002-4432-4707; Qiao, You-Lin/0000-0001-6380-0871;
Clavel, Jacqueline/0000-0002-3616-7676; Hattinger,
Claudia/0000-0002-9316-5095; Beane Freeman, Laura/0000-0003-1294-4124;
Joseph, Vijai/0000-0002-7933-151X; Brooks-Wilson,
Angela/0000-0003-1009-6408; Weiderpass, Elisabete/0000-0003-2237-0128;
Abnet, Christian/0000-0002-3008-7843; Purdue, Mark/0000-0003-1177-3108;
Jin, Li/0000-0002-4546-2415; Savage, Sharon/0000-0001-6006-0740; Krogh,
Vittorio/0000-0003-0122-8624
FU Intramural Research Program of the National Institutes of Health
FX This study was supported by the Intramural Research Program of the
National Institutes of Health.
NR 35
TC 14
Z9 14
U1 7
U2 63
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 DEC
PY 2015
VL 107
IS 12
AR djv279
DI 10.1093/jnci/djv279
PG 11
WC Oncology
SC Oncology
GA CZ2YN
UT WOS:000366970900015
PM 26464424
ER
PT J
AU Wentzensen, N
Fetterman, B
Castle, PE
Schiffman, M
Wood, SN
Stiemerling, E
Tokugawa, D
Bodelon, C
Poitras, N
Lorey, T
Kinney, W
AF Wentzensen, Nicolas
Fetterman, Barbara
Castle, Philip E.
Schiffman, Mark
Wood, Shannon N.
Stiemerling, Eric
Tokugawa, Diane
Bodelon, Clara
Poitras, Nancy
Lorey, Thomas
Kinney, Walter
TI p16/Ki-67 Dual Stain Cytology for Detection of Cervical Precancer in
HPV-Positive Women
SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Article
ID HUMAN-PAPILLOMAVIRUS DNA; RANDOMIZED CONTROLLED-TRIAL; CANCER
PRECURSORS; INTRAEPITHELIAL NEOPLASIA; PREDICTIVE VALUES;
SCREENING-TESTS; FOLLOW-UP; PERFORMANCE; COLPOSCOPY; PREVENTION
AB Background: Human papillomavirus (HPV)-based cervical cancer screening requires triage markers to decide who should be referred to colposcopy. p16/Ki-67 dual stain cytology has been proposed as a biomarker for cervical precancers. We evaluated the dual stain in a large population of HPV-positive women.
Methods: One thousand five hundred and nine HPV-positive women screened with HPV/cytology cotesting at Kaiser Permanente California were enrolled into a prospective observational study in 2012. Dual stain cytology was performed on residual Surepath material, and slides were evaluated for dual stain-positive cells. Disease endpoints were ascertained from the clinical database at KPNC. We evaluated the clinical performance of the assay among all HPV-positive women and among HPV-positive, cytology-negative women. We used internal benchmarks for clinical management to evaluate the clinical relevance of the dual stain assay. We evaluated sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the dual stain compared with Pap cytology. All statistical tests were two-sided.
Results: The dual stain had lower positivity (45.9%) compared with cytology at an ASC-US threshold (53.4%). For detection of CIN2+, the dual stain had similar sensitivity (83.4% vs 76.6%, P = .1), and statistically higher specificity (58.9% vs 49.6%, P < .001), PPV (21.0% vs 16.6%, P < .001), and NPV (96.4% vs 94.2%, P = .01) compared with cytology. Similar patterns were observed for CIN3+. Women with a positive test had high enough risk for referral to colposcopy, while the risk for women with negative tests was below a one-year return threshold based on current US management guidelines.
Conclusion: Dual stain cytology showed good risk stratification for all HPV-positive women and for HPV-positive women with normal cytology. Additional follow-up is needed to determine how long dual stain negative women remain at low risk of precancer.
C1 [Wentzensen, Nicolas; Schiffman, Mark; Wood, Shannon N.; Bodelon, Clara] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Fetterman, Barbara; Stiemerling, Eric; Tokugawa, Diane; Poitras, Nancy; Lorey, Thomas] Kaiser Permanente, TPMG Reg Lab, Berkeley, CA USA.
[Castle, Philip E.] Global Coalit Cerv Canc, Arlington, VA USA.
[Castle, Philip E.] Albert Einstein Coll Med, Bronx, NY 10467 USA.
[Kinney, Walter] Kaiser Permanente Med Care Program, Div Gynecol Oncol, Oakland, CA USA.
RP Wentzensen, N (reprint author), NCI, Div Canc Epidemiol & Genet, 9609 Med Ctr Dr,Room 7-E114, Bethesda, MD 20892 USA.
EM wentzenn@mail.nih.gov
NR 26
TC 6
Z9 8
U1 1
U2 5
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 DEC
PY 2015
VL 107
IS 12
AR djv257
DI 10.1093/jnci/djv257
PG 8
WC Oncology
SC Oncology
GA CZ2YN
UT WOS:000366970900002
PM 26376685
ER
PT J
AU Yamazaki, Y
Kodama, S
Kakizaki, S
Yamada, M
Negishi, M
AF Yamazaki, Y.
Kodama, S.
Kakizaki, S.
Yamada, M.
Negishi, M.
TI IGFBP1 mediates pregnane X receptor-induced morphological changes and
migration of hepatocellular carcinoma cells
SO JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY
LA English
DT Meeting Abstract
C1 [Yamazaki, Y.; Kodama, S.; Negishi, M.] NIEHS, Pharmacogenet Sect, Lab Reprod & Dev Toxicol, NIH, Res Triangle Pk, NC 27709 USA.
[Yamazaki, Y.; Kakizaki, S.; Yamada, M.] Gunma Univ, Grad Sch Med, Dept Med & Mol Sci, Maebashi, Gunma 371, Japan.
[Kodama, S.] Tohoku Univ, Grad Sch Pharmaceut Sci, Lab Pharmacotherapy Life Style Related Dis, Sendai, Miyagi 980, Japan.
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 0815-9319
EI 1440-1746
J9 J GASTROEN HEPATOL
JI J. Gastroenterol. Hepatol.
PD DEC
PY 2015
VL 30
SU 4
SI SI
MA 1010
BP 329
EP 329
PG 1
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA CX4NI
UT WOS:000365677202018
ER
PT J
AU Kirklin, JK
Naftel, DC
Pagani, FD
Kormos, RL
Stevenson, LW
Blume, ED
Myers, SL
Miller, MA
Baldwin, JT
Young, JB
AF Kirklin, James K.
Naftel, David C.
Pagani, Francis D.
Kormos, Robert L.
Stevenson, Lynne W.
Blume, Elizabeth D.
Myers, Susan L.
Miller, Marissa A.
Baldwin, J. Timothy
Young, James B.
TI Seventh INTERMACS annual report: 15,000 patients and counting
SO JOURNAL OF HEART AND LUNG TRANSPLANTATION
LA English
DT Article
DE advanced heart failure; destination therapy; INTERMACS; mechanical
support; ventricular assist device
ID VENTRICULAR ASSIST DEVICE; THROMBOSIS
AB The seventh annual report of the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) summarizes the first 9 years of patient enrollment. The Registry includes >15,000 patients from 158 participating hospitals. Trends in device strategy, patient profile at implant and survival are presented. Risk factors for mortality with continuous-flow pumps are updated, and the major causes/modes of death are presented. The adverse event burden is compared between eras, and health-related quality of life is reviewed. A detailed analysis of outcomes after mechanical circulatory support for ambulatory heart failure is presented. Recent summary data from PediMACS and MedaMACS is included. With the current continuous-flow devices, survival at 1 and 2 years is 80% and 70%, respectively. (C) 2015 International Society for Heart and Lung Transplantation. All rights reserved.
C1 [Kirklin, James K.; Naftel, David C.; Myers, Susan L.] Univ Alabama Birmingham, Dept Surg, Birmingham, AL 35294 USA.
[Pagani, Francis D.] Univ Michigan, Dept Surg, Ann Arbor, MI 48109 USA.
[Kormos, Robert L.] Univ Pittsburgh, Presbyterian Univ Hosp, Med Ctr, Dept Surg, Pittsburgh, PA USA.
[Stevenson, Lynne W.] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
[Blume, Elizabeth D.] Boston Childrens Hosp, Dept Pediat, Boston, MA USA.
[Miller, Marissa A.; Baldwin, J. Timothy] NHLBI, Div Cardiovasc Dis, Adv Technol & Surg Branch, Bethesda, MD 20892 USA.
[Young, James B.] Cleveland Clin Fdn, Lerner Coll Med, Dept Med, Cleveland, OH 44195 USA.
RP Kirklin, JK (reprint author), Univ Alabama Birmingham, Dept Surg, 1900 Univ Blvd, Birmingham, AL 35294 USA.
EM jkirklin@uab.edu
FU National Heart, Lung and Blood Institute [HHSN2682011000250]
FX D.C.N. is a consultant for HeartWare and F.D.P. participates in contract
research managed by the University of Michigan for HeartWare and
Thoratec. The remaining authors have no conflicts of interest to
disclose. This analysis and the INTERMACS device database are funded by
a contract grant (HHSN2682011000250) from the National Heart, Lung and
Blood Institute.
NR 4
TC 142
Z9 143
U1 10
U2 18
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1053-2498
EI 1557-3117
J9 J HEART LUNG TRANSPL
JI J. Heart Lung Transplant.
PD DEC
PY 2015
VL 34
IS 12
SI SI
BP 1495
EP 1504
DI 10.1016/j.healun.2015.10.003
PG 10
WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery;
Transplantation
SC Cardiovascular System & Cardiology; Respiratory System; Surgery;
Transplantation
GA CZ2SU
UT WOS:000366955700001
PM 26520247
ER
PT J
AU Jeffries, N
Miller, MA
Taddei-Peters, WC
Burke, C
Baldwin, JT
Young, JB
AF Jeffries, Neal
Miller, Marissa A.
Taddei-Peters, Wendy C.
Burke, Catherine
Baldwin, J. Timothy
Young, James B.
TI What is the truth behind pump thrombosis in the HeartMate II device? A
National Heart, Lung, and Blood Institute perspective based on data from
the Interagency Registry for Mechanically Assisted Circulatory Support
SO JOURNAL OF HEART AND LUNG TRANSPLANTATION
LA English
DT Editorial Material
C1 [Jeffries, Neal; Miller, Marissa A.; Taddei-Peters, Wendy C.; Burke, Catherine; Baldwin, J. Timothy] NHLBI, Bethesda, MD 20892 USA.
[Young, James B.] Cleveland Clin, Cleveland, OH 44106 USA.
RP Jeffries, N (reprint author), NHLBI, NIH, Room 9194,MSC 7913,6701 Rockledge Dr, Bethesda, MD 20892 USA.
EM nealjeff@nhIbi.nih.gov
FU PHS HHS [HHSN268201100025C]
NR 15
TC 5
Z9 5
U1 1
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1053-2498
EI 1557-3117
J9 J HEART LUNG TRANSPL
JI J. Heart Lung Transplant.
PD DEC
PY 2015
VL 34
IS 12
SI SI
BP 1505
EP 1510
DI 10.1016/j.healun.2015.10.036
PG 6
WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery;
Transplantation
SC Cardiovascular System & Cardiology; Respiratory System; Surgery;
Transplantation
GA CZ2SU
UT WOS:000366955700002
PM 26681119
ER
PT J
AU Malicdan, MCV
Vilboux, T
Stephen, J
Maglic, D
Mian, L
Konzman, D
Guo, J
Yildirimli, D
Bryant, J
Fischer, R
Zein, WM
Snow, J
Vemulapalli, M
Mullikin, JC
Toro, C
Solomon, BD
Niederhuber, JE
Gahl, WA
Gunay-Aygun, M
AF Malicdan, May Christine V.
Vilboux, Thierry
Stephen, Joshi
Maglic, Dino
Mian, Luhe
Konzman, Daniel
Guo, Jennifer
Yildirimli, Deniz
Bryant, Joy
Fischer, Roxanne
Zein, Wadih M.
Snow, Joseph
Vemulapalli, Meghana
Mullikin, James C.
Toro, Camilo
Solomon, Benjamin D.
Niederhuber, John E.
Gahl, William A.
Gunay-Aygun, Meral
CA NISC Comparative Sequencing Progra
TI Mutations in human homologue of chicken talpid3 gene (KIAA0586) cause a
hybrid ciliopathy with overlapping features of Jeune and Joubert
syndromes
SO JOURNAL OF MEDICAL GENETICS
LA English
DT Article
ID ASPHYXIATING THORACIC DYSTROPHY; CILIA; PROTEINS; ABNORMALITIES;
EXPRESSION; REVEALS; ENCODES; DISEASE; MUTANT; CEP120
AB Background In chicken, loss of TALPID3 results in non-functional cilia and short-rib polydactyly syndrome. This phenotype is caused by a frameshift mutation in the chicken ortholog of the human KIAA0586 gene, which encodes a novel coiled-coil domain protein essential for primary ciliogenesis, suggesting that KIAA0586 can be associated with ciliopathy in human beings.
Methods In our patients with ciliopathy (http://www.clinicaltrials.gov: NCT00068224), we have collected extensive clinical and neuroimaging data from affected individuals, and performed whole exome sequencing on DNA from affected individuals and their parents. We analysed gene expression on fibroblast cell line, and determined the effect of gene mutation on ciliogenesis in cells derived from patients.
Results We identified biallelic mutations in the human TALPID3 ortholog, KIAA0586, in six children with findings of overlapping Jeune and Joubert syndromes. Fibroblasts cultured from one of the patients with Jeune-Joubert syndrome exhibited more severe cilia defects than fibroblasts from patients with only Joubert syndrome; this difference was reflected in KIAA0586 RNA expression levels. Rescue of the cilia defect with full-length wild type KIAA0586 indicated a causal link between cilia formation and KIAA0586 function.
Conclusions Our results show that biallelic deleterious mutations in KIAA0586 lead to Joubert syndrome with or without Jeune asphyxiating thoracic dystrophy. Furthermore, our results confirm that KIAA0586/TALPID3 is essential in cilia formation in human beings, expand the KIAA0586 phenotype to include features of Jeune syndrome and provide a pathogenetic connection between Joubert and Jeune syndromes, based on aberrant ciliogenesis.
C1 [Malicdan, May Christine V.; Toro, Camilo; Gahl, William A.] NIH, Undiagnosed Dis Program, Common Fund, Off Director, Bethesda, MD 20892 USA.
[Malicdan, May Christine V.; Vilboux, Thierry; Stephen, Joshi; Maglic, Dino; Mian, Luhe; Konzman, Daniel; Guo, Jennifer; Yildirimli, Deniz; Bryant, Joy; Fischer, Roxanne; Gahl, William A.; Gunay-Aygun, Meral] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA.
[Vilboux, Thierry; Solomon, Benjamin D.] Inova Translat Med Inst, Div Med Genom, Falls Church, VA USA.
[Zein, Wadih M.] NEI, Ophthalm Genet & Visual Funct Branch, NIH, Bethesda, MD 20892 USA.
[Snow, Joseph] NIMH, Off Clin Director, NIH, Bethesda, MD 20892 USA.
[Vemulapalli, Meghana; Mullikin, James C.; NISC Comparative Sequencing Progra] NHGRI, NISC, NIH, Bethesda, MD 20892 USA.
[Gahl, William A.; Gunay-Aygun, Meral] NHGRI, Off Clin Director, NIH, Bethesda, MD 20892 USA.
[Niederhuber, John E.] Inova Translat Med Inst, Inova Hlth Syst, Falls Church, VA USA.
RP Gunay-Aygun, M (reprint author), NHGRI, NIH, 10 Ctr Dr,Bldg 10,Rm 10C103C, Bethesda, MD 20892 USA.
EM mgaygun@mail.nih.gov
FU Intramural Research Programs of National Human Genome Research
Institute; National Eye Institute; National Institute of Mental Health
of National Institutes of Health, Bethesda, Maryland, USA
FX This research was supported by the Intramural Research Programs of the
National Human Genome Research Institute, National Eye Institute and the
National Institute of Mental Health of the National Institutes of
Health, Bethesda, Maryland, USA. We also thank the patients and their
families for participating in this study.
NR 30
TC 6
Z9 6
U1 3
U2 6
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0022-2593
EI 1468-6244
J9 J MED GENET
JI J. Med. Genet.
PD DEC
PY 2015
VL 52
IS 12
BP 830
EP 839
DI 10.1136/jmedgenet-2015-103316
PG 10
WC Genetics & Heredity
SC Genetics & Heredity
GA CZ2YF
UT WOS:000366970000006
PM 26386044
ER
PT J
AU Hoque, MT
Shah, A
More, V
Miller, DS
Bendayan, R
AF Hoque, Md. Tozammel
Shah, Arpit
More, Vijay
Miller, David S.
Bendayan, Reina
TI In vivo and ex vivo regulation of breast cancer resistant protein (Bcrp)
by peroxisome proliferator-activated receptor alpha (Ppar alpha) at the
blood-brain barrier
SO JOURNAL OF NEUROCHEMISTRY
LA English
DT Article
DE Blood-brain barrier; brain capillaries; breast cancer resistant protein;
nuclear receptors; peroxisome proliferator-activated receptor alpha;
regulation of drug transport
ID XENOBIOTIC EFFLUX TRANSPORTERS; MICROVESSEL ENDOTHELIAL-CELLS;
ARYL-HYDROCARBON RECEPTOR; MEDIATED UP-REGULATION; P-GLYCOPROTEIN;
NUCLEAR RECEPTORS; ABC TRANSPORTERS; RODENT BRAIN; EXPRESSION;
LOCALIZATION
AB Breast cancer resistance protein (Bcrp/Abcg2) localized at the blood-brain barrier (BBB) limits permeability into the brain of many xenobiotics, including pharmacological agents. Peroxisome proliferator-activated receptor alpha (Ppar alpha), a ligand-activated transcription factor, primarily involved in lipid metabolism, has been shown to regulate the functional expression of Bcrp in human cerebral microvascular endothelial cells (hCMEC/D3). The aim of this study was to investigate ex vivo and in vivo, the regulation of Bcrp by Ppar alpha in an intact BBB. Ex vivo quantitative real-time PCR and immunoblot analyses showed significant up-regulation of Abcg2/Bcrp mRNA and protein levels in CD-1 mouse brain capillaries incubated with clofibrate, alpha Ppar alpha ligand. Fluorescence-based transport assays in CD-1 and C57BL/6 brain capillaries showed that exposure to clofibrate significantly increased Bcrp transport activity. This increase was not observed in capillaries isolated from Ppar alpha knockout mice. In vivo, we found: i) significant Bcrp protein up-regulation in clofibrate-dosed CD-1 and C57BL/6 capillary lysates, but no effect in Ppar alpha knockout capillary lysates, and ii) significantly increased Bcrp transport activity in capillaries isolated from clofibrate-treated mice. These results demonstrate an increase in Bcrp functional expression by Ppar alpha in brain capillaries, and suggest that Ppar alpha is another nuclear receptor that can contribute to the regulation of membrane efflux transporters and drug permeability at the BBB.
C1 [Hoque, Md. Tozammel; Shah, Arpit; Bendayan, Reina] Univ Toronto, Dept Pharmaceut Sci, Leslie Dan Fac Pharm, Toronto, ON, Canada.
[More, Vijay; Miller, David S.] NIEHS, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA.
RP Bendayan, R (reprint author), Univ Toronto, Dept Pharmaceut Sci, Leslie Dan Fac Pharm, Toronto, ON, Canada.
EM r.bendayan@utoronto.ca
FU Canadian Institutes of Health Research (CIHR) [MOP56976]; Ontario HIV
Treatment Network (OHTN) Career Scientist award; CIHR Strategic Training
Program in Biological Therapeutics; Intramural Research Program of the
National Institute of Environmental Health Sciences, National Institutes
of Health
FX This research is supported by a grant from the Canadian Institutes of
Health Research (CIHR, Grant No. MOP56976) awarded to Dr Reina Bendayan.
Dr Bendayan is the recipient of the Ontario HIV Treatment Network (OHTN)
Career Scientist award. Arpit Shah is the recipient of a graduate
scholarship from the CIHR Strategic Training Program in Biological
Therapeutics. Supported by the Intramural Research Program of the
National Institute of Environmental Health Sciences, National Institutes
of Health.
NR 47
TC 2
Z9 2
U1 3
U2 7
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0022-3042
EI 1471-4159
J9 J NEUROCHEM
JI J. Neurochem.
PD DEC
PY 2015
VL 135
IS 6
BP 1113
EP 1122
DI 10.1111/jnc.13389
PG 10
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA CZ6DT
UT WOS:000367192100006
PM 26465636
ER
PT J
AU Li, YZ
Bader, M
Tamargo, I
Rubovitch, V
Tweedie, D
Pick, CG
Greig, NH
AF Li, Yazhou
Bader, Miaad
Tamargo, Ian
Rubovitch, Vardit
Tweedie, David
Pick, Chaim G.
Greig, Nigel H.
TI Liraglutide is neurotrophic and neuroprotective in neuronal cultures and
mitigates mild traumatic brain injury in mice
SO JOURNAL OF NEUROCHEMISTRY
LA English
DT Article
DE apoptosis; cAMP-response element binding protein; glucagon-like
peptide-1; liraglutide; neuroprotection; traumatic brain injury
ID GLUCAGON-LIKE PEPTIDE-1; REVERSES BEHAVIORAL IMPAIRMENTS;
ALZHEIMERS-DISEASE; NEURODEGENERATIVE DISORDERS; PARKINSONS-DISEASE;
COGNITIVE DEFICITS; GENE-EXPRESSION; ANIMAL-MODEL; HEAD-INJURY;
BETA-CELLS
AB Traumatic brain injury (TBI), a brain dysfunction for which there is no present effective treatment, is often caused by a concussive impact to the head and affects an estimated 1.7 million Americans annually. Our laboratory previously demonstrated that exendin-4, a long-lasting glucagon-like peptide 1 receptor (GLP-1R) agonist, has neuroprotective effects in cellular and animal models of TBI. Here, we demonstrate neurotrophic and neuroprotective effects of a different GLP-1R agonist, liraglutide, in neuronal cultures and a mouse model of mild TBI (mTBI). Liraglutide promoted dose-dependent proliferation in SH-SY5Y cells and in a GLP-1R over-expressing cell line at reduced concentrations. Pre-treatment with liraglutide rescued neuronal cells from oxidative stress-and glutamate excitotoxicity-induced cell death. Liraglutide produced neurotrophic and neuroprotective effects similar to those of exendin-4 in vitro. The cAMP/PKA/pCREB pathway appears to play an important role in this neuroprotective activity of liraglutide. Furthermore, our findings in cell culture were well-translated in a weight drop mTBI mouse model. Post-treatment with a clinically relevant dose of liraglutide for 7 days in mice ameliorated memory impairments caused by mTBI when evaluated 7 and 30 days post trauma. These data cross-validate former studies of exendin-4 and suggest that liraglutide holds therapeutic potential for the treatment of mTBI.
C1 [Li, Yazhou; Tamargo, Ian; Tweedie, David; Greig, Nigel H.] NIA, Translat Gerontol Branch, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
[Bader, Miaad; Rubovitch, Vardit; Pick, Chaim G.] Tel Aviv Univ, Sackler Fac Med, Dept Anat & Anthropol, IL-69978 Tel Aviv, Israel.
[Pick, Chaim G.] Tel Aviv Univ, Sagol Sch Neurosci, IL-69978 Tel Aviv, Israel.
RP Li, YZ (reprint author), Biomed Res Ctr, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM liyaz@mail.nih.gov; greign@mail.nih.gov
FU Intramural Research Program of the National Institute on Aging, National
Institutes of Health; Ari and Regine Aprijaskis Fund at Tel-Aviv
University; Israel Science Foundation [108/09]
FX This research was supported in part by (i) the Intramural Research
Program of the National Institute on Aging, National Institutes of
Health, (ii) the Ari and Regine Aprijaskis Fund at Tel-Aviv University,
and (iii) a grant from the Israel Science Foundation, grant number
108/09. No competing financial interests exist.
NR 82
TC 13
Z9 13
U1 4
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0022-3042
EI 1471-4159
J9 J NEUROCHEM
JI J. Neurochem.
PD DEC
PY 2015
VL 135
IS 6
BP 1203
EP 1217
DI 10.1111/jnc.13169
PG 15
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA CZ6DT
UT WOS:000367192100014
PM 25982185
ER
PT J
AU Civiero, L
Cirnaru, MD
Beilina, A
Rodella, U
Russo, I
Belluzzi, E
Lobbestael, E
Reyniers, L
Hondhamuni, G
Lewis, PA
Van den Haute, C
Baekelandt, V
Bandopadhyay, R
Bubacco, L
Piccoli, G
Cookson, MR
Taymans, JM
Greggio, E
AF Civiero, Laura
Cirnaru, Maria Daniela
Beilina, Alexandra
Rodella, Umberto
Russo, Isabella
Belluzzi, Elisa
Lobbestael, Evy
Reyniers, Lauran
Hondhamuni, Geshanthi
Lewis, Patrick A.
Van den Haute, Chris
Baekelandt, Veerle
Bandopadhyay, Rina
Bubacco, Luigi
Piccoli, Giovanni
Cookson, Mark R.
Taymans, Jean-Marc
Greggio, Elisa
TI Leucine-rich repeat kinase 2 interacts with p21-activated kinase 6 to
control neurite complexity in mammalian brain
SO JOURNAL OF NEUROCHEMISTRY
LA English
DT Article
DE LRRK2; neurodegeneration; neuronal cytoskeleton; p21-activated kinases;
Parkinson's disease
ID PARKINSONS-DISEASE; CYTOPLASMIC LOCALIZATION; DOPAMINERGIC-NEURONS;
ACTIN CYTOSKELETON; 14-3-3 BINDING; LRRK2 CONTROLS; GTP-BINDING;
MOUSE-BRAIN; PHOSPHORYLATION; INHIBITION
AB Leucine-rich repeat kinase 2 (LRRK2) is a causative gene for Parkinson's disease, but the physiological function and the mechanism(s) by which the cellular activity of LRRK2 is regulated are poorly understood. Here, we identified p21-activated kinase 6 (PAK6) as a novel interactor of the GTPase/ROC domain of LRRK2. p21-activated kinases are serine-threonine kinases that serve as targets for the small GTP binding proteins Cdc42 and Rac1 and have been implicated in different morphogenetic processes through remodeling of the actin cytoskeleton such as synapse formation and neuritogenesis. Using an in vivo neuromorphology assay, we show that PAK6 is a positive regulator of neurite outgrowth and that LRRK2 is required for this function. Analyses of post-mortem brain tissue from idiopathic and LRRK2 G2019S carriers reveal an increase in PAK6 activation state, whereas knock-out LRRK2mice display reduced PAK6 activation and phosphorylation of PAK6 substrates. Taken together, these results support a critical role of LRRK2 GTPase domain in cytoskeletal dynamics in vivo through the novel interactor PAK6, and provide a valuable platform to unravel the mechanism underlying LRRK2-mediated pathophysiology.
C1 [Civiero, Laura; Rodella, Umberto; Russo, Isabella; Belluzzi, Elisa; Bubacco, Luigi; Greggio, Elisa] Univ Padua, Dept Biol, I-35131 Padua, Italy.
[Cirnaru, Maria Daniela; Piccoli, Giovanni] Univ Vita Salute San Raffaele, Milan, Italy.
[Beilina, Alexandra; Cookson, Mark R.] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
[Rodella, Umberto; Lobbestael, Evy; Reyniers, Lauran; Van den Haute, Chris; Baekelandt, Veerle; Taymans, Jean-Marc] Katholieke Univ Leuven, Lab Neurobiol & Gene Therapy, Leuven, Belgium.
[Hondhamuni, Geshanthi; Bandopadhyay, Rina] UCL, Dept Mol Neurosci, Reta Lila Weston Inst Neurol Studies, Inst Neurol, London, England.
[Lewis, Patrick A.] Univ Reading, Sch Pharm, Reading, Berks, England.
[Lewis, Patrick A.] UCL, Inst Neurol, Dept Mol Neurosci, London, England.
[Van den Haute, Chris] Katholieke Univ Leuven, Leuven Viral Vector Core, Leuven, Belgium.
RP Greggio, E (reprint author), Univ Padua, Dept Biol, I-35131 Padua, Italy.
EM cookson@mail.nih.gov; jean-marc.taymans@inserm.fr;
elisa.greggio@unipd.it
RI Bandopadhyay, Rina /C-7926-2009;
OI Russo, Isabella/0000-0002-6151-2451; Lewis, Patrick/0000-0003-4537-0489;
Belluzzi, Elisa/0000-0003-1129-2574; Bubacco, Luigi/0000-0001-7927-9208
FU Michael J Fox Foundation; Telethon - Italy [GGP12237]; CARIPLO
Foundation [2011-0540]; EMBO fellowship [MBO ASTF 526-2012];
FWO-Vlaanderen [G.0666.09, KAN2012 1.5.216.12]; IWT [SBO/80020,
SBO/100042]; Fund Druwe-Eerdekens; Intramural Research Program of the
NIH, National Institute on Aging; MRC [MR/L010933/1]; Parkinson's UK
[F1002]; Wellcome Trust/MRC Joint Call in Neurodegeneration award
[WT089698]; University of Sheffield; MRC Protein Phosphorylation Unit at
the University of Dundee
FX We are grateful to the Michael J Fox Foundation for supporting this
study. We also thank the financial support of Telethon - Italy (Grant
no. GGP12237) and the CARIPLO Foundation (grant 2011-0540). LC was
supported by a short-term EMBO fellowship (MBO ASTF 526-2012/Award). We
thank the FWO-Vlaanderen (FWO projects G.0666.09, KAN2012 1.5.216.12 and
fellowship to JMT), the IWT SBO/80020 and SBO/100042 projects and the
Fund Druwe-Eerdekens managed by the King Baudouin Foundation for their
support. This research was supported in part by the Intramural Research
Program of the NIH, National Institute on Aging. This project is
supported by an MRC grant to PAL (MR/L010933/1). PAL is a Parkinson's UK
research fellow (grant F1002). This work was supported in part by the
Wellcome Trust/MRC Joint Call in Neurodegeneration award (WT089698) to
the UK Parkinson's Disease Consortium (UKPDC) whose members are from the
UCL Institute of Neurology, the University of Sheffield and the MRC
Protein Phosphorylation Unit at the University of Dundee. We thank
Professor Johan Hofkens and Charlotte David (Molecular Imaging and
Photonics, KU Leuven) for the use of the confocal laser scanning
microscope. We also acknowledge the technical assistance of Fangye Gao
and Caroline Van Heijningen and the Leuven Viral Vector Core
(http://www.kuleuven.be/molmed/lvvc/vectorproduction.html) for the
production of LV and AAV vectors. We gratefully thank Dr. Heather
Melrose for providing LRRK2 knock-out mice. The authors have no conflict
of interest to declare.
NR 75
TC 5
Z9 5
U1 2
U2 9
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0022-3042
EI 1471-4159
J9 J NEUROCHEM
JI J. Neurochem.
PD DEC
PY 2015
VL 135
IS 6
BP 1242
EP 1256
DI 10.1111/jnc.13369
PG 15
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA CZ6DT
UT WOS:000367192100017
PM 26375402
ER
PT J
AU Tempero, M
AF Tempero, Margaret
TI Paying Less for High-Value Care-Are You Kidding Me?
SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK
LA English
DT Editorial Material
C1 [Tempero, Margaret] UCSF, Med, San Francisco, CA 94143 USA.
[Tempero, Margaret] UCSF, Pancreas Ctr, San Francisco, CA USA.
[Tempero, Margaret] NCI, Clin Oncol Study Sect, Bethesda, MD 20892 USA.
[Tempero, Margaret] Mayo Clin, Pancreas SPOREs, Rochester, MN USA.
[Tempero, Margaret] UAB Minnesota, Minneapolis, MN USA.
[Tempero, Margaret] Univ Arizona, GI SPORE, Tucson, AZ 85721 USA.
[Tempero, Margaret] Lustgarten Fdn, Bethpage, NY USA.
[Tempero, Margaret] V Fdn, Cary, NY USA.
[Tempero, Margaret] Alberta Canada Canc Board, Edmonton, AB, Canada.
[Tempero, Margaret] UNMC, Eppley Canc Ctr, Omaha, NE USA.
[Tempero, Margaret] UCSF, Div Med Oncol, San Francisco, CA USA.
[Tempero, Margaret] UCSF, Helen Diller Family Comprehens Canc Ctr, San Francisco, CA USA.
RP Tempero, M (reprint author), UCSF, Med, San Francisco, CA 94143 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU HARBORSIDE PRESS
PI COLD SPRING HARBOR
PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA
SN 1540-1405
EI 1540-1413
J9 J NATL COMPR CANC NE
JI J. Natl. Compr. Cancer Netw.
PD DEC
PY 2015
VL 13
IS 12
BP 1453
EP 1453
PG 1
WC Oncology
SC Oncology
GA CZ3RG
UT WOS:000367021100001
PM 26656513
ER
PT J
AU Hoa, M
Friedman, RA
Fisher, LM
Derebery, MJ
AF Hoa, Michael
Friedman, Rick A.
Fisher, Laurel M.
Derebery, M. Jennifer
TI Prognostic Implications of and Audiometric Evidence for Hearing
Fluctuation in Meniere's Disease
SO LARYNGOSCOPE
LA English
DT Article
DE Meniere's disease; hearing loss; hearing fluctuation; efficacy;
treatment; clinical trial
ID ENDOLYMPHATIC SAC DRAINAGE; TERM-FOLLOW-UP; HYDROPS; STEROIDS; ATTACKS;
THRESHOLDS; MANAGEMENT
AB Objectives/Hypothesis: 1) To establish criteria for significant hearing fluctuation by assessing the range and occurrence of hearing fluctuations over the course of Meniere's disease; 2) to determine if audiometric evidence exists to support the notion that Meniere's disease is a pathophysiologic process involving the whole cochlea; and 3) to suggest prognostic implications for initial hearing fluctuation in patients with Meniere's disease.
Study Design: Retrospective case series review.
Methods: A total of 488 patients diagnosed by 1995 American Academy of Otolaryngology-Head and Neck Surgery Meniere's disease criteria for whom audiometric data were prospectively collected (2 cohorts: 341 and 146 patients initially seen between April 2002 to July 2003 and between January to December 2010, respectively). Based on several definitions for significant hearing fluctuation, change in hearing was categorized as "same," "worse," or "better" between any two consecutive evaluations. The relationship of initial hearing fluctuation to future hearing fluctuation and future hearing loss was evaluated.
Results: Hearing fluctuation was evident in Meniere's disease patients with heterogeneous audiometric follow-up; and the characteristics of these hearing fluctuations, including the mean incidence, is described. Audiometric data suggests that there is a high congruence in Meniere's disease between changes in low-and high-frequency thresholds. Initial hearing fluctuation is associated with the occurrence of future and more frequent hearing fluctuations.
Conclusion: Understanding the range of hearing fluctuations establishes a basis for determining audiometric thresholds used in evaluating future therapeutic trials aimed at the prevention of hearing loss in Meniere's disease. This knowledge will also inform the counseling directed toward patients diagnosed with Meniere's disease.
C1 [Hoa, Michael] Georgetown Univ, Dept Otolaryngol Head & Neck Surg, Med Ctr, Washington, DC 20007 USA.
[Hoa, Michael] NIDCD, NIH, Otolaryngol Surgeon Sci Dev Program, Bethesda, MD USA.
[Friedman, Rick A.; Fisher, Laurel M.] Univ So Calif, Dept Otolaryngol, Keck Sch Med, Los Angeles, CA USA.
[Derebery, M. Jennifer] House Clin, Los Angeles, CA USA.
RP Hoa, M (reprint author), Georgetown Univ, Dept Otolaryngol Head & Neck Surg, Med Ctr, 3800 Reservoir Rd,NW,Gorman Bldg,1st Fl, Washington, DC 20007 USA.
EM michael.hoa@nih.gov
NR 24
TC 2
Z9 3
U1 0
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0023-852X
EI 1531-4995
J9 LARYNGOSCOPE
JI Laryngoscope
PD DEC
PY 2015
VL 125
SU 12
BP S1
EP S12
DI 10.1002/lary.25579
PG 12
WC Medicine, Research & Experimental; Otorhinolaryngology
SC Research & Experimental Medicine; Otorhinolaryngology
GA CZ6CK
UT WOS:000367188500001
PM 26343803
ER
PT J
AU Panda, D
Cherry, S
AF Panda, Debasis
Cherry, Sara
TI A genome-wide RNAi screening method to discover novel genes involved in
virus infection
SO METHODS
LA English
DT Article
DE siRNA screening protocol; Image-based screening; Virus-host
interactions; Arrayed screen; High-content screening
ID WEST-NILE-VIRUS; HOST FACTORS; FALSE DISCOVERY; HIT SELECTION; DENGUE
VIRUS; REPLICATION; REVEALS; ENTRY
AB Systematic and comprehensive analysis of host cell proteins involved in virus infection has been difficult in large part due to the lack of robust unbiased methods for their identification. Recent technological breakthroughs allowing development of cell-based genetic screens have greatly facilitated our understanding of virus-host interactions. These include instrumentation for processing in microtiter plates (e.g., 384 well), coupled with sensitive readers and off-the-shelf analysis and informatics pipelines. Because viruses are a significant threat to human health, a better understanding of the cellular factors that impact infection would pave the way for the development of new therapeutics. Here we describe the development and implementation of a genome-wide siRNA screen against a virus using human cells. (C) 2015 Elsevier Inc. All rights reserved.
C1 [Panda, Debasis] NIAID, NIH, Viral Dis Lab, Bethesda, MD 20892 USA.
[Cherry, Sara] Univ Penn, Dept Microbiol, Philadelphia, PA 19104 USA.
RP Panda, D (reprint author), Bldg 33,Room 1E13,33 North Dr, Bethesda, MD 20892 USA.
EM debasis.panda@nih.gov; cherrys@mail.med.upenn.edu
FU National Institute of Health [R01AI074951, U54AI057168, R21AI103441,
R01AI095500]; Burroughs Wellcome Investigators in the Pathogenesis of
Infectious Disease Award
FX This work was supported by National Institute of Health Grants
R01AI074951, U54AI057168, R21AI103441 and R01AI095500 to SC. SC is a
recipient of the Burroughs Wellcome Investigators in the Pathogenesis of
Infectious Disease Award.
NR 21
TC 2
Z9 2
U1 1
U2 4
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1046-2023
EI 1095-9130
J9 METHODS
JI Methods
PD DEC
PY 2015
VL 91
BP 75
EP 81
DI 10.1016/j.ymeth.2015.07.002
PG 7
WC Biochemical Research Methods; Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA CZ0GM
UT WOS:000366783100010
PM 26164699
ER
PT J
AU Taruscio, D
Groft, SC
Cederroth, H
Melegh, B
Lasko, P
Kosaki, K
Baynam, G
McCray, A
Gahl, WA
AF Taruscio, Domenica
Groft, Stephen C.
Cederroth, Helene
Melegh, Bela
Lasko, Paul
Kosaki, Kenjiro
Baynam, Gareth
McCray, Alexa
Gahl, William A.
TI Undiagnosed Diseases Network International (UDNI): White paper for
global actions to meet patient needs
SO MOLECULAR GENETICS AND METABOLISM
LA English
DT Editorial Material
DE Undiagnosed; Global health; Rare diseases; Omics; Ontology; Diagnosis
ID PROGRAM
AB In 2008, the National Institutes of Health's (NIH) Undiagnosed Disease Program (UDP) was initiated to provide diagnoses for individuals who had long sought one without success. As a result of two international conferences (Rome 2014 and Budapest 2015), the Undiagnosed Diseases Network International (UDNI) was established, modeled in part after the NIH UDP. Undiagnosed diseases are a global health issue, calling for an international scientific and healthcare effort. To meet this demand, the UDNI has built a consensus framework of principles, best practices and governance; the Board of Directors reflects its international character, as it includes experts from Australia, Canada, Hungary, Italy, Japan and the USA. The UDNI involves centers with internationally recognized expertise, and its scientific resources and know-how aim to fill the knowledge gaps that impede diagnosis. Consequently, the UDNI fosters the translation of research into medical practice. Active patient involvement is critical; the Patient Advisory Group is expected to play an increasing role in UDNI activities. All information for physicians and patients will be available at the UDNI website. (C) 2015 Published by Elsevier Inc.
C1 [Taruscio, Domenica] Ist Super Sanita, Natl Ctr Rare Dis, I-00161 Rome, Italy.
[Groft, Stephen C.] NIH, Natl Ctr Adv Translat Sci, Bethesda, MD USA.
[Cederroth, Helene] Wilhelm Fdn, Brottby, Sweden.
[Melegh, Bela] Univ Pecs, Dept Med Genet, Pecs, Hungary.
[Lasko, Paul] McGill Univ, Dept Biol, Montreal, PQ H3A 1B1, Canada.
[Kosaki, Kenjiro] Keio Univ, Sch Med, Ctr Med Genet, Tokyo, Japan.
[Baynam, Gareth] Princess Margaret Hosp, Perth, WA, Australia.
[Baynam, Gareth] King Edward Mem Hosp, Perth, WA, Australia.
[Baynam, Gareth] WA Dept Hlth, Publ Hlth Div, Off Populat Hlth, Melbourne, Vic, Australia.
[Baynam, Gareth] Telethon Kids Inst, Perth, WA, Australia.
[Baynam, Gareth] Western Australian Registry Dev Anomalies, Perth, WA, Australia.
[Baynam, Gareth] Univ Western Australia, Sch Paediat & Child Hlth, Perth, WA 6009, Australia.
[Baynam, Gareth] Murdoch Univ, Inst Immunol & Infect Dis, Perth, WA, Australia.
[McCray, Alexa] Harvard Univ, Sch Med, Dept Med, Ctr Biomed Informat, Boston, MA USA.
[Gahl, William A.] NHGRI, NIH Undiagnosed Dis Program, NIH, Bethesda, MD USA.
RP Taruscio, D (reprint author), Ist Super Sanita, Natl Ctr Rare Dis, Viale Regina Elena 299, I-00161 Rome, Italy.
EM domenica.taruscio@iss.it
NR 7
TC 10
Z9 10
U1 1
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 DEC
PY 2015
VL 116
IS 4
BP 223
EP 225
DI 10.1016/j.ymgme.2015.11.003
PG 3
WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research &
Experimental
SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental
Medicine
GA CZ7KH
UT WOS:000367277800001
PM 26596705
ER
PT J
AU Tekola-Ayele, F
Doumatey, AP
Shriner, D
Bentley, AR
Chen, GJ
Zhou, J
Fasanmade, O
Johnson, T
Oli, J
Okafor, G
Eghan, BA
Agyenim-Boateng, K
Adebamowo, C
Amoah, A
Acheampong, J
Adeyemo, A
Rotimi, CN
AF Tekola-Ayele, Fasil
Doumatey, Ayo P.
Shriner, Daniel
Bentley, Amy R.
Chen, Guanjie
Zhou, Jie
Fasanmade, Olufemi
Johnson, Thomas
Oli, Johnnie
Okafor, Godfrey
Eghan, Benjami A., Jr.
Agyenim-Boateng, Kofi
Adebamowo, Clement
Amoah, Albert
Acheampong, Joseph
Adeyemo, Adebowale
Rotimi, Charles N.
TI Genome-wide association study identifies African-ancestry specific
variants for metabolic syndrome
SO MOLECULAR GENETICS AND METABOLISM
LA English
DT Article
DE Metabolic syndrome; Pleiotropy; Genome-wide association study; African
ancestry
ID CARBONIC-ANHYDRASE INHIBITORS; ENDOPLASMIC-RETICULUM STRESS; ACTIVATED
RECEPTOR-GAMMA; ALPHA-T-CATENIN; TRANSCRIPTION FACTORS;
INSULIN-RESISTANCE; DIABETES-MELLITUS; ADIPOCYTE DIFFERENTIATION;
SUSCEPTIBILITY GENES; QUANTITATIVE TRAITS
AB The metabolic syndrome (MetS) is a constellation of metabolic disorders that increase the risk of developing several diseases including type 2 diabetes and cardiovascular diseases. Although genome-wide association studies (GWAS) have successfully identified variants associated with individual traits comprising MetS, the genetic basis and pathophysiological mechanisms underlying the clustering of these traits remain unclear. We conducted GWAS of MetS in 1427 Africans from Ghana and Nigeria followed by replication testing and meta-analysis in another continental African sample from Kenya. Further replication testing was performed in an African American sample from the Atherosclerosis Risk in Communities (ARIC) study. We found two African-ancestry specific variants that were significantly associated with MetS: SNP rs73989312[A] near CA10 that conferred increased risk (P = 3.86 x 10(-8), OR = 6.80) and SNP rs77244975[C] in CTNNA3 that conferred protection against MetS (P = 1.63 x 10(-8), OR = 0.15). Given the exclusive expression of CA10 in the brain, our CA10 finding strengthens previously reported link between brain function and MetS. We also identified two variants that are not African specific: rs76822696[A] near RALYL associated with increased MetS risk (P = 7.37 x 10(-9), OR = 1.59) and rs7964157[T] near KSR2 associated with reduced MetS risk (P = 4.52 x 10(-8), P-meta = 7.82 x 10(-9), OR = 0.53). The KSR2 locus displayed pleiotropic associations with triglyceride and measures of blood pressure. Rare KSR2 mutations have been reported to be associated with early onset obesity and insulin resistance. Finally, we replicated the LPL and CETP loci previously found to be associated with MetS in Europeans. These findings provide novel insights into the genetics of MetS in Africans and demonstrate the utility of conducting trans-ethnic disease gene mapping studies for testing the cosmopolitan significance of GWAS signals of cardio-metabolic traits. Published by Elsevier Inc.
C1 [Tekola-Ayele, Fasil; Doumatey, Ayo P.; Shriner, Daniel; Bentley, Amy R.; Chen, Guanjie; Zhou, Jie; Adeyemo, Adebowale; Rotimi, Charles N.] NHGRI, Ctr Res Genom & Global Hlth, NIH, Bethesda, MD 20892 USA.
[Fasanmade, Olufemi; Johnson, Thomas] Univ Lagos, Lagos, Nigeria.
[Oli, Johnnie; Okafor, Godfrey] Univ Nigeria, Teaching Hosp, Enugu, Nigeria.
[Eghan, Benjami A., Jr.; Agyenim-Boateng, Kofi; Acheampong, Joseph] Univ Sci & Technol, Dept Med, Kumasi, Ghana.
[Adebamowo, Clement] Univ Maryland, Sch Med, Dept Epidemiol & Publ Hlth, Baltimore, MD 21201 USA.
[Amoah, Albert] Univ Ghana, Sch Med, Dept Med, Accra, Ghana.
RP Tekola-Ayele, F (reprint author), NHGRI, Ctr Res Genom & Global Hlth, NIH, Bldg 12A,Room 4047,12 South Dr, Bethesda, MD 20892 USA.
EM ayeleft@mail.nih.gov; rotimic@mail.nih.gov
OI Adeyemo, Adebowale/0000-0002-3105-3231; Tekola-Ayele,
Fasil/0000-0003-4194-9370
FU Intramural Research Program of National Institutes of Health in Center
for Research on Genomics and Global Health (CRGGH); National Human
Genome Research Institute; National Institute of Diabetes and Digestive
and Kidney Diseases; Center for Information Technology; Office of the
Director at National Institutes of Health [1ZIAHG200362]; NIH from
Office of Research on Minority Health [3T37TW00041-03S2]; National
Center for Research Resources; National Heart, Lung, and Blood Institute
[HHSN268201100005C, HHSN268201100006C, HHSN268201100007C,
HHSN268201100008C, HHSN268201100009C, HHSN268201100010C,
HHSN268201100011C, HHSN268201100012C]; Human Genome Research Institute
grant [U01HG004402]
FX This work was supported in part by the Intramural Research Program of
the National Institutes of Health in the Center for Research on Genomics
and Global Health (CRGGH). The CRGGH is supported by the National Human
Genome Research Institute, the National Institute of Diabetes and
Digestive and Kidney Diseases, the Center for Information Technology,
and the Office of the Director at the National Institutes of Health
(1ZIAHG200362). Support for participant recruitment and initial genetic
studies of the AADM study was provided by NIH grant No. 3T37TW00041-03S2
from the Office of Research on Minority Health. The project was also
supported in part by the National Center for Research Resources. The
Atherosclerosis Risk in Communities (ARIC) Study is carried out as a
collaborative study supported by National Heart, Lung, and Blood
Institute contracts (HHSN268201100005C, HHSN268201100006C,
HHSN268201100007C, HHSN268201100008C, HHSN268201100009C,
HHSN268201100010C, HHSN268201100011C, and HHSN268201100012C). The
authors thank the staff and participants of the ARIC study for their
important contributions. Funding for ARIC Gene Environment Association
Studies (GENEVA) was provided by National Human Genome Research
Institute grant U01HG004402 (E. Boerwinkle).
NR 87
TC 2
Z9 2
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 DEC
PY 2015
VL 116
IS 4
BP 305
EP 313
DI 10.1016/j.ymgme.2015.10.008
PG 9
WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research &
Experimental
SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental
Medicine
GA CZ7KH
UT WOS:000367277800012
PM 26507551
ER
PT J
AU Rizvi, SM
Salam, N
Geng, J
Qi, Y
Bream, JH
Duggal, P
Hussain, SK
Martinson, J
Wolinsky, S
Carrington, M
Raghavan, M
AF Rizvi, Syed Monem
Salam, Nasir
Geng, Jie
Qi, Ying
Bream, Jay H.
Duggal, Priya
Hussain, Shehnaz K.
Martinson, Jeremy
Wolinsky, Steven
Carrington, Mary
Raghavan, Malini
TI Distinct assembly profiles of HLA-B molecules
SO MOLECULAR IMMUNOLOGY
LA English
DT Meeting Abstract
CT 8th International Workshop on Antigen Processing and Presentation
CY JUN 10-13, 2014
CL Philadelphia, PA
C1 [Rizvi, Syed Monem; Salam, Nasir; Geng, Jie; Raghavan, Malini] Univ Michigan, Sch Med, Dept Microbiol & Immunol, Ann Arbor, MI 48109 USA.
[Qi, Ying; Carrington, Mary] SAIC Frederick Inc, Canc & Inflammat Program, Expt Immunol Lab, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
[Qi, Ying; Carrington, Mary] Ragon Inst MGH MIT & Harvard, Cambridge, MA 02139 USA.
[Bream, Jay H.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD 21205 USA.
[Duggal, Priya] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA.
[Hussain, Shehnaz K.] Univ Calif Los Angeles, Fielding Sch Publ Hlth, Dept Epidemiol, Los Angeles, CA 90095 USA.
[Hussain, Shehnaz K.] Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA.
[Martinson, Jeremy] Univ Pittsburgh, Med Ctr, Sch Med, Dept Pathol, Pittsburgh, PA 15261 USA.
[Wolinsky, Steven] Northwestern Univ, Feinberg Sch Med, Div Infect Dis, Chicago, IL 60611 USA.
EM malinir@umich.edu
NR 0
TC 0
Z9 0
U1 0
U2 1
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0161-5890
J9 MOL IMMUNOL
JI Mol. Immunol.
PD DEC
PY 2015
VL 68
IS 2
BP 136
EP 136
PN A
PG 1
WC Biochemistry & Molecular Biology; Immunology
SC Biochemistry & Molecular Biology; Immunology
GA CZ0AO
UT WOS:000366767700028
ER
PT J
AU Wei, JJ
Gibbs, J
Bennink, JR
Yewdell, JW
AF Wei, Jiajie
Gibbs, James
Bennink, Jack R.
Yewdell, Jonathan W.
TI Illuminating DRiPs with GFP
SO MOLECULAR IMMUNOLOGY
LA English
DT Meeting Abstract
CT 8th International Workshop on Antigen Processing and Presentation
CY JUN 10-13, 2014
CL Philadelphia, PA
C1 [Wei, Jiajie; Gibbs, James; Bennink, Jack R.; Yewdell, Jonathan W.] Natl Inst Allergy & Infect, Bethesda, MD 20892 USA.
EM jyewdell@nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0161-5890
J9 MOL IMMUNOL
JI Mol. Immunol.
PD DEC
PY 2015
VL 68
IS 2
BP 142
EP 143
PN A
PG 2
WC Biochemistry & Molecular Biology; Immunology
SC Biochemistry & Molecular Biology; Immunology
GA CZ0AO
UT WOS:000366767700048
ER
PT J
AU Cho, KJ
Furuta, K
Walseng, E
Roche, PA
AF Cho, Kyung-Jin
Furuta, Kazuyuki
Walseng, Even
Roche, Paul A.
TI Ubiquitination by march-I prevents pMHC-II recycling
SO MOLECULAR IMMUNOLOGY
LA English
DT Meeting Abstract
CT 8th International Workshop on Antigen Processing and Presentation
CY JUN 10-13, 2014
CL Philadelphia, PA
C1 [Cho, Kyung-Jin; Furuta, Kazuyuki; Walseng, Even; Roche, Paul A.] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA.
EM paul.roche@nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0161-5890
J9 MOL IMMUNOL
JI Mol. Immunol.
PD DEC
PY 2015
VL 68
IS 2
BP 149
EP 150
PN A
PG 2
WC Biochemistry & Molecular Biology; Immunology
SC Biochemistry & Molecular Biology; Immunology
GA CZ0AO
UT WOS:000366767700069
ER
PT J
AU Morozov, GI
Zhao, HY
Mage, MG
Boyd, LF
Hildebrand, WH
McMurtrey, C
Schuck, P
Natarajan, K
Margulies, DH
AF Morozov, Giora I.
Zhao, Huayung
Mage, Michael G.
Boyd, Lisa F.
Hildebrand, William H.
McMurtrey, Curtis
Schuck, Peter
Natarajan, Kannan
Margulies, David H.
TI Tapasin-related protein TAPBP-R interacts directly with peptide-free
MHC-I/beta 2-microglobulin complexes and is released by high affinity
peptides
SO MOLECULAR IMMUNOLOGY
LA English
DT Meeting Abstract
CT 8th International Workshop on Antigen Processing and Presentation
CY JUN 10-13, 2014
CL Philadelphia, PA
C1 [Morozov, Giora I.; Mage, Michael G.; Boyd, Lisa F.; Natarajan, Kannan; Margulies, David H.] NIAID, Mol Biol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA.
[Zhao, Huayung; Schuck, Peter] NIBIB, Dynam Macromol Assembly Sect, Lab Cellular Imaging & Macromol Biophys, NIH, Bethesda, MD 20892 USA.
[Hildebrand, William H.; McMurtrey, Curtis] Univ Oklahoma, Hlth Sci Ctr, Dept Microbiol & Immunol, Oklahoma City, OK 73104 USA.
EM giora.morozov@nih.gov; zhaoh3@mail.nih.gov; mmage@niaid.nih.gov;
lboyd@niaid.nih.gov; William-Hildebrand@ouhsc.edu;
Curtis-McMurtrey@ouhsc.edu; schuckp@mail.nih.gov;
knatarajan@niaid.nih.gov; dhm@nih.gov
NR 0
TC 0
Z9 0
U1 1
U2 5
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0161-5890
J9 MOL IMMUNOL
JI Mol. Immunol.
PD DEC
PY 2015
VL 68
IS 2
BP 149
EP 149
PN A
PG 1
WC Biochemistry & Molecular Biology; Immunology
SC Biochemistry & Molecular Biology; Immunology
GA CZ0AO
UT WOS:000366767700068
ER
PT J
AU Jung, M
Dunbar, CE
Winkler, T
AF Jung, Moonjung
Dunbar, Cynthia E.
Winkler, Thomas
TI Modeling Human Bone Marrow Failure Syndromes Using Pluripotent Stem
Cells and Genome Engineering
SO MOLECULAR THERAPY
LA English
DT Review
ID DIAMOND-BLACKFAN ANEMIA; PAROXYSMAL-NOCTURNAL HEMOGLOBINURIA; FAMILIAL
PLATELET DISORDER; ACUTE MYELOGENOUS LEUKEMIA; FANCONI-ANEMIA;
DYSKERATOSIS-CONGENITA; HEMATOPOIETIC PROGENITORS; APLASTIC-ANEMIA;
MYELODYSPLASTIC SYNDROMES; IPS CELLS
AB The combination of epigenetic reprogramming with advanced genome editing technologies opened a new avenue to study disease mechanisms, particularly of disorders with depleted target tissue. Bone marrow failure syndromes (BMFS) typically present with a marked reduction of peripheral blood cells due to a destroyed or dysfunctional bone marrow compartment. Somatic and germline mutations have been etiologically linked to many cases of BMFS. However, without the ability to study primary patient material, the exact pathogenesis for many entities remained fragmentary. Capturing the pathological genotype in induced pluripotent stem cells (iPSCs) allows studying potential developmental defects leading to a particular phenotype. The lack of hematopoietic stem and progenitor cells in these patients can also be overcome by differentiating patientderived iPSCs into hematopoietic lineages. With fast growing genome editing techniques, such as CRISPR/Cas9, correction of disease-causing mutations in iPSCs or introduction of mutations in cells from healthy individuals enable comparative studies that may identify other genetic or epigenetic events contributing to a specific disease phenotype. In this review, we present recent progresses in disease modeling of inherited and acquired BMFS using reprogramming and genome editing techniques. We also discuss the challenges and potential shortcomings of iPSC-based models for hematological diseases.
C1 [Jung, Moonjung; Dunbar, Cynthia E.; Winkler, Thomas] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
RP Winkler, T (reprint author), NHLBI, Hematol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM winklert@nhlbi.nih.gov
FU Division of Intramural Research at the National Heart, Lung, and Blood
Institute
FX The authors were supported by the Division of Intramural Research at the
National Heart, Lung, and Blood Institute. The authors declare no
conflict of interest.
NR 118
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U1 4
U2 17
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
EI 1525-0024
J9 MOL THER
JI Mol. Ther.
PD DEC
PY 2015
VL 23
IS 12
BP 1832
EP 1842
DI 10.1038/mt.2015.180
PG 11
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA CZ3IH
UT WOS:000366997200007
PM 26435409
ER
PT J
AU Case, LK
Pineda, J
Ramachandran, VS
AF Case, Laura K.
Pineda, Jaime
Ramachandran, Vilayanur S.
TI Common coding and dynamic interactions between observed, imagined, and
experienced motor and somatosensory activity
SO NEUROPSYCHOLOGIA
LA English
DT Article
DE Simulation; Mirror neuron system; Sensory referral; Motor referral;
Somatosensation; Imagery
ID POSITRON-EMISSION-TOMOGRAPHY; MIRROR-TOUCH SYNAESTHESIA; PHANTOM LIMB
PAIN; TRANSCRANIAL MAGNETIC STIMULATION; MENTAL ROTATION; CORTICOSPINAL
EXCITABILITY; CORTICAL EXCITABILITY; SENSORIMOTOR CORTEX; EXECUTED
MOVEMENTS; FUNCTIONAL-ANATOMY
AB Motor imagery and perception - considered generally as forms of motor simulation - share overlapping neural representations with motor production. While much research has focused on the extent of this "common coding," less attention has been paid to how these overlapping representations interact. How do imagined, observed, or produced actions influence one another, and how do we maintain control over our perception and behavior? In the first part of this review we describe interactions between motor production and motor simulation, and explore apparent regulatory mechanisms that balance these processes. Next, we consider the somatosensory system. Numerous studies now support a "sensory mirror system" comprised of neural representations activated by either afferent sensation or vicarious sensation. In the second part of this review we summarize evidence for shared representations of sensation and sensory simulation (including imagery and observed sensation), and suggest that similar interactions and regulation of simulation occur in the somatosensory domain as in the motor domain. We suggest that both motor and somatosensory simulations are flexibly regulated to support simulations congruent with our sensorimotor experience and goals and suppress or separate the influence of those that are not. These regulatory mechanisms are frequently revealed by cases of brain injury but can also be employed to facilitate sensorimotor rehabilitation. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
C1 [Case, Laura K.; Ramachandran, Vilayanur S.] Univ Calif San Diego, Ctr Brain & Cognit, San Diego, CA 92103 USA.
[Case, Laura K.] NIH, Pain & Integrat Neurosci Branch, Natl Ctr Complementary & Integrat Hlth, Bethesda, MD 20892 USA.
[Pineda, Jaime] Univ Calif San Diego, Dept Cognit Sci, San Diego, CA 92103 USA.
RP Case, LK (reprint author), NIH, Natl Ctr Complementary & Integrat Hlth, Bldg 10, Bethesda, MD 20892 USA.
EM laura.case@nih.gov
FU University of California, San Diego; National Center for Complementary
and Integrative Health (NCCIH)
FX The authors thank Pat Church land, Piotr Winkielman, Claire Laubacher,
and M Catherine Bushnell for assistance and helpful conversations. The
first author thanks the University of California, San Diego and the
National Center for Complementary and Integrative Health (NCCIH) for
support during the preparation of the manuscript. The views presented in
this paper are solely those of the authors and do not necessarily
reflect views of NCCIH.
NR 201
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U2 15
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 DEC
PY 2015
VL 79
SI SI
BP 233
EP 245
DI 10.1016/j.neuropsychologia.2015.04.005
PN B
PG 13
WC Behavioral Sciences; Neurosciences; Psychology, Experimental
SC Behavioral Sciences; Neurosciences & Neurology; Psychology
GA CZ1QC
UT WOS:000366879400008
PM 25863237
ER
PT J
AU Kim, BC
Kim, MK
Han, K
Lee, SY
Lee, SH
Ko, SH
Kwon, HS
Merchant, AT
Yim, HW
Lee, WC
Park, YG
Park, YM
AF Kim, Byung Chul
Kim, Mee Kyoung
Han, Kyungdo
Lee, Sae-Young
Lee, Seung-Hwan
Ko, Seung-Hyun
Kwon, Hyuk-Sang
Merchant, Anwar T.
Yim, Hyeon Woo
Lee, Won-Chul
Park, Yong Gyu
Park, Yong-Moon
TI Low muscle mass is associated with metabolic syndrome only in nonobese
young adults: the Korea National Health and Nutrition Examination Survey
2008-2010
SO NUTRITION RESEARCH
LA English
DT Article
DE Low muscle mass; Sarcopenia; Metabolic syndrome; Obesity; Young adults;
Insulin resistance
ID CARDIOVASCULAR-DISEASE RISK; SKELETAL-MUSCLE; SARCOPENIC OBESITY;
INSULIN-RESISTANCE; POSTMENOPAUSAL WOMEN; BODY-COMPOSITION; MEN;
STRENGTH; GLUCOSE; TESTOSTERONE
AB Little is known about the relationship between body composition and metabolic risk factors in young adults. We hypothesized that low muscle mass (LMM) is associated with metabolic syndrome (MetS) and its components in young adults and that the associations vary by obesity. A cross-sectional analysis was conducted using the Korea National Health and Nutrition Examination Survey data. In total, 5300 young adults aged 19 to 39 years were evaluated. Low muscle mass was defined as an appendicular skeletal muscle mass/weight less than 1 SD below the mean for each participant's corresponding sex and age group. Obesity was defined as a body mass index greater than or equal to 25 kg/m(2). The prevalence of LMM was higher in obese than nonobese participants (37.6% vs 9.6%). In the nonobese participants, the prevalence of MetS, high waist circumference, high triglycerides, and high blood pressure was significantly greater in the LMM group than in the high muscle mass group. In the nonobese group, compared with high muscle mass participants, those with LMM had odds ratios for MetS of 3.6 (95% confidence interval, 1.48-8.76; P < .001) and 3.6 (95% confidence interval, 1.48-8.71; P < .001) in men and women, respectively, after adjusting for confounding factors. However, no significant association of LMM with MetS or its components was found in obese participants. In conclusion, our results suggest that young adults with LMM may have a high risk of MetS, especially when they are nonobese. Interventions aimed at increasing muscle mass at younger ages may have the potential to reduce MetS. Published by Elsevier Inc.
C1 [Kim, Byung Chul] Catholic Univ Korea, Sch Med, Seoul, South Korea.
[Kim, Byung Chul] Catholic Univ Korea, Dept Surg, Seoul, South Korea.
[Kim, Mee Kyoung; Lee, Seung-Hwan; Ko, Seung-Hyun; Kwon, Hyuk-Sang] Catholic Univ Korea, Dept Internal Med, Div Endocrinol & Metab, Seoul, South Korea.
[Han, Kyungdo; Park, Yong Gyu] Catholic Univ Korea, Dept Biostat, Seoul, South Korea.
[Lee, Sae-Young] Korea Ctr Dis Control & Prevent, Korea Natl Inst Hlth, Ctr Immunol & Pathol, Div Aids, Osong, Chungbuk, South Korea.
[Lee, Sae-Young; Yim, Hyeon Woo; Lee, Won-Chul; Park, Yong-Moon] Catholic Univ Korea, Dept Prevent Med, Seoul, South Korea.
[Merchant, Anwar T.; Park, Yong-Moon] Univ S Carolina, Arnold Sch Publ Hlth, Dept Epidemiol & Biostat, Columbia, SC 29208 USA.
[Park, Yong-Moon] NIEHS, NIH, Dept Hlth & Human Serv, Epidemiol Branch, Res Triangle Pk, NC 27709 USA.
RP Park, YM (reprint author), NIEHS, Epidemiol Branch, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA.
EM mark.park@nih.gov
OI Lee, Seung-Hwan/0000-0002-3964-3877; PARK, YONG-MOON/0000-0002-5879-6879
NR 36
TC 1
Z9 1
U1 0
U2 2
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0271-5317
J9 NUTR RES
JI Nutr. Res.
PD DEC
PY 2015
VL 35
IS 12
BP 1070
EP 1078
DI 10.1016/j.nutres.2015.09.020
PG 9
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA CZ1RQ
UT WOS:000366883400005
PM 26602833
ER
PT J
AU Risso, DS
Howard, L
VanWaes, C
Drayna, D
AF Risso, Davide S.
Howard, Louisa
VanWaes, Carter
Drayna, Dennis
TI A potential trigger for pine mouth: a case of a homozygous
phenylthiocarbamide taster
SO NUTRITION RESEARCH
LA English
DT Article
DE Dysgeusia; Pine nuts; PTC; TAS2R38; Taste disturbance
ID NUTS; SENSITIVITY; DYSGEUSIA; CONSUMERS; MARKERS
AB Pine mouth, also known as pine nut syndrome, is an uncommon dysgeusia that generally begins 12 to 48 hours after consuming pine nuts. It is characterized by a bitter metallic taste, usually amplified by the consumption of other foods, which lasts 2 to 4 weeks. Recent findings have correlated this disorder with the consumption of nuts of the species Pinus armandii, but no potential triggers or common underlying medical causes have been identified in individuals affected by this syndrome. We report a 23-year-old patient affected by pine mouth who also underwent a phenylthiocarbamide taste test and was found to be a taster for this compound. TAS2R38 genotyping demonstrated that this subject was a homozygous carrier of the proline-alanine-valine taster haplotype.
We, therefore, hypothesize that homozygous phenylthiocarbamide taster status may be a potential contributor for pine mouth events. Although based on a single observation, this research suggests a connection between genetically determined bitter taste perception and the occurrence of pine nut dysgeusia events. Published by Elsevier Inc.
C1 [Risso, Davide S.; Drayna, Dennis] Natl Inst Deafness & Other Commun Disorders, NIH, Bethesda, MD 20892 USA.
[Risso, Davide S.] Univ Bologna, Dept BiGeA, Lab Mol Anthropol, I-40126 Bologna, Italy.
[Risso, Davide S.] Univ Bologna, Ctr Genome Biol, I-40126 Bologna, Italy.
[Howard, Louisa] NIAID, NIH, Bethesda, MD 20892 USA.
[VanWaes, Carter] Natl Inst Deafness & Other Commun Disorders, NIH, Clin Genom Unit, Bethesda, MD 20892 USA.
[VanWaes, Carter] Natl Inst Deafness & Other Commun Disorders, NIH, Tumor Biol Sect, Head & Neck Surg Branch, Bethesda, MD 20892 USA.
RP Risso, DS (reprint author), Natl Inst Deafness & Other Commun Disorders, NIH, Bethesda, MD 20892 USA.
EM davide.risso@nih.gov
OI Risso, Davide/0000-0001-9848-8996
FU National Institute on Deafness and Other Communication Disorders
intramural grant [Z1A-000046-15, ZIA-DC-000075]
FX DR, CVW, and DD were supported by the National Institute on Deafness and
Other Communication Disorders intramural grant numbers Z1A-000046-15 and
ZIA-DC-000075.
NR 20
TC 2
Z9 2
U1 3
U2 12
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0271-5317
J9 NUTR RES
JI Nutr. Res.
PD DEC
PY 2015
VL 35
IS 12
BP 1122
EP 1125
DI 10.1016/j.nutres.2015.09.011
PG 4
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA CZ1RQ
UT WOS:000366883400011
PM 26463018
ER
PT J
AU Kumar, S
Tchounwou, PB
AF Kumar, Sanjay
Tchounwou, Paul B.
TI Molecular mechanisms of cisplatin cytotoxicity in acute promyelocytic
leukemia cells
SO ONCOTARGET
LA English
DT Article
DE cisplatin; APL cell line; cell cycle modulation; AP-1 and p53
ID ARSENIC TRIOXIDE; DNA-DAMAGE; MITOCHONDRIAL PATHWAY; INDUCED APOPTOSIS;
OXIDATIVE STRESS; RESISTANCE; CHEMOTHERAPY; HYPERTHERMIA; EXPRESSION;
THERAPY
AB Cis-diamminedichloroplatinum (II) (cisplatin) is a widely used anti-tumor drug for the treatment of a broad range of human malignancies with successful therapeutic outcomes for head and neck, ovarian, and testicular cancers. It has been found to inhibit cell cycle progression and to induce oxidative stress and apoptosis in acute promyelocytic leukemia (APL) cells. However, its molecular mechanisms of cytotoxic action are poorly understood. We hypothesized that cisplatin induces cytotoxicity through DNA adduct formation, oxidative stress, transcriptional factors (p53 and AP-1), cell cycle regulation, stress signaling and apoptosis in APL cells. We used the APL cell line as a model, and applied a variety of molecular tools to elucidate the cytotoxic mode of action of cisplatin. We found that cisplatin inhibited cell proliferation by a cytotoxicity, characterized by DNA damage and modulation of oxidative stress. Cisplatin also activated p53 and phosphorylated activator protein (AP-1) component, c-Jun at serine (63, 73) residue simultaneously leading to cell cycle arrest through stimulation of p21 and down regulation of cyclins and cyclin dependent kinases in APL cell lines. It strongly activated the intrinsic pathway of apoptosis through alteration of the mitochondrial membrane potential, release of cytochrome C, and up-regulation of caspase 3 activity. It also down regulated the p38MAPK pathway. Overall, this study highlights the molecular mechanisms that underline cisplatin toxicity to APL cells, and provides insights into selection of novel targets and/or design of therapeutic agents to treat APL.
C1 [Kumar, Sanjay; Tchounwou, Paul B.] Jackson State Univ, Coll Sci Engn & Technol, NIH NIMHD RCMI Ctr Environm Hlth, Cell & Toxicogen Res Lab, Jackson, MS 39217 USA.
RP Tchounwou, PB (reprint author), Jackson State Univ, Coll Sci Engn & Technol, NIH NIMHD RCMI Ctr Environm Hlth, Cell & Toxicogen Res Lab, Jackson, MS 39217 USA.
EM paul.b.tchounwou@jsums.edu
FU National Institutes of Health NIMHD through the RCMI-Center for
Environmental Health at Jackson State University [G12MD007581]
FX This research was financially supported by National Institutes of Health
NIMHD Grant No. G12MD007581, through the RCMI-Center for Environmental
Health at Jackson State University.
NR 32
TC 3
Z9 3
U1 1
U2 6
PU IMPACT JOURNALS LLC
PI ALBANY
PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA
SN 1949-2553
J9 ONCOTARGET
JI Oncotarget
PD DEC 1
PY 2015
VL 6
IS 38
BP 40734
EP 40746
PG 13
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA CY0SF
UT WOS:000366115500027
PM 26486083
ER
PT J
AU Al-Holou, SN
Tucker, WR
Agron, E
Clemons, TE
Cukras, C
Ferris, FL
Chew, EY
AF Al-Holou, Shaza N.
Tucker, William R.
Agron, Elvira
Clemons, Traci E.
Cukras, Catherine
Ferris, Frederick L., III
Chew, Emily Y.
CA Age-Related Eye Dis Study 2 Res
TI The Association of Statin Use with Age-Related Macular Degeneration
Progression The Age-Related Eye Disease Study 2 Report Number 9
SO OPHTHALMOLOGY
LA English
DT Article
ID COA REDUCTASE INHIBITORS; C-REACTIVE PROTEIN; CORONARY-HEART-DISEASE;
BRUCHS MEMBRANE; LOWERING DRUGS; MEDICATION USE; UNITED-STATES; EYE
DISEASE; RISK; MACULOPATHY
AB Purpose: To evaluate the association of statin use with progression of age-related macular degeneration (AMD).
Design: Preplanned, prospective cohort study within a controlled clinical trial of oral supplementation for age-related eye diseases.
Participants: Age-Related Eye Disease Study 2 (AREDS2) participants, aged 50 to 85 years.
Methods: Factors, including age, gender, smoking status, aspirin use, and history of diabetes, hypertension, heart disease, angina, and stroke-all known to be associated with statin use-were included in a logistic regression model to estimate propensity scores for each participant. Age-adjusted proportional hazards regression models, with and without propensity score matching, were performed to evaluate the association of statin use with progression to late AMD. Analyses adjusting for the competing risk of death were also performed.
Main Outcome Measures: Baseline and annual stereoscopic fundus photographs were assessed centrally by masked graders for the development of late AMD, either neovascular AMD or geographic atrophy (GA).
Results: Of the 3791 participants (2462 with bilateral large drusen and 1329 with unilateral late AMD at baseline), 1659 (43.8%) were statin users. The overall analysis, with no matching of propensity scores and no adjustment for death as a competing risk, showed that statin use was not associated with progression to late AMD (hazard ratio [HR], 1.08; 95% confidence interval [CI], 0.83-1.41; P = 0.56). When matched for propensity scores and adjusted for death as a competing risk, the result was not statistically significant (HR, 0.81; 95% CI, 0.55-1.20; P = 0.29). Furthermore, subgroup analyses of persons with or without late AMD at baseline and the various components of late AMD (neovascular AMD, central GA, or any GA) also showed no statistically significant association of statin use with progression to AMD.
Conclusions: Statin use was not statistically significantly associated with progression to late AMD in the AREDS2 participants, and these findings are consistent with findings in the majority of previous studies. Statins have been demonstrated to reduce the risk of cardiovascular disease, but our data do not provide evidence of a beneficial effect on slowing AMD progression. (C) 2015 Published by Elsevier on behalf of the American Academy of Ophthalmology.
C1 [Al-Holou, Shaza N.; Agron, Elvira; Cukras, Catherine; Ferris, Frederick L., III; Chew, Emily Y.] NEI, Clin Trials Branch, Div Epidemiol & Clin Applicat, NIH, Bethesda, MD 20892 USA.
[Tucker, William R.] NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA.
[Clemons, Traci E.] EMMES Corp, Rockville, MD USA.
RP Chew, EY (reprint author), NEI, NIH, Bldg 10,CRC Room 3-2531,10 Ctr Dr,MSC 1204, Bethesda, MD 20892 USA.
EM echew@nei.nih.gov
FU National Eye Institute/National Institutes of Health (NIH), Department
of Health and Human Services, Bethesda Maryland [HHS-N-260-2005-0007-C,
NO1-EY-5-0007]; NIH institute: Office of Dietary Supplements, National
Center for Complementary and Alternative Medicine; NIH institute:
National Institute on Aging; National Heart, Lung, and Blood Institute;
NIH institute: National Institute of Neurological Disorders and Stroke;
NIH; Pfizer Inc.; Doris Duke Charitable Foundation; Alexandria Real
Estate Equities, Inc.; Mr. and Mrs. Joel S. Marcus; Howard Hughes
Medical Institute
FX Supported by intramural program funds and contracts from the National
Eye Institute/National Institutes of Health (NIH), Department of Health
and Human Services, Bethesda Maryland (contract HHS-N-260-2005-0007-C;
ADB Contract NO1-EY-5-0007). Funds were generously contributed to these
contracts by the following NIH institutes: Office of Dietary
Supplements, National Center for Complementary and Alternative Medicine;
National Institute on Aging; National Heart, Lung, and Blood Institute;
and National Institute of Neurological Disorders and Stroke. The sponsor
and funding organization participated in the design and conduct of the
study; data collection, management, analysis, and interpretation; and
the preparation, review, and approval of the manuscript. This research
was made possible through the NIH Medical Research Scholars Program, a
public-private partnership supported jointly by the NIH and generous
contributions to the Foundation for the NIH 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. For a complete list, please see the
Foundation website at:
http://fnih.org/work/education-training-0/medical-research-scholars-prog
ram.
NR 46
TC 1
Z9 1
U1 3
U2 6
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0161-6420
EI 1549-4713
J9 OPHTHALMOLOGY
JI Ophthalmology
PD DEC
PY 2015
VL 122
IS 12
BP 2490
EP 2496
DI 10.1016/j.ophtha.2015.08.028
PG 7
WC Ophthalmology
SC Ophthalmology
GA CZ4EZ
UT WOS:000367057500028
PM 26435335
ER
PT J
AU Ying, GS
Maguire, MG
Daniel, E
Ferris, FL
Jaffe, GJ
Grunwald, JE
Toth, CA
Huang, JY
Martin, DF
AF Ying, Gui-shuang
Maguire, Maureen G.
Daniel, Ebenezer
Ferris, Frederick L.
Jaffe, Glenn J.
Grunwald, Juan E.
Toth, Cynthia A.
Huang, Jiayan
Martin, Daniel F.
CA Comparison Age-Related Macular
TI Association of Baseline Characteristics and Early Vision Response with
2-Year Vision Outcomes in the Comparison of AMD Treatments Trials (CATT)
SO OPHTHALMOLOGY
LA English
DT Article
ID DEGENERATION TREATMENTS TRIALS; VISUAL-ACUITY LOSS; MACULAR
DEGENERATION; RANIBIZUMAB; BEVACIZUMAB; AFLIBERCEPT; THERAPY
AB Purpose: To evaluate the association of baseline characteristics and early visual acuity (VA) response with visual outcomes at years 1 or 2 in the Comparison of Age-Related Macular Degeneration (AMD) Treatments Trials (CATT).
Design: Secondary analysis of CATT.
Participants: The 1185 CATT participants with baseline VA of 20/25 to 20/320. Methods: Participants were assigned to ranibizumab or bevacizumab and to 1 of 3 dosing regimens. Associations of baseline characteristics and early VA response (week 4 or 12) with VA response at years 1 or 2 were assessed by R-2 from linear regression analyses. Patients who had a poor initial response (VA 20/ 40 or worse with persistent fluid and without >= 1-line VA gain) were defined as candidates for changing treatment.
Main Outcome Measures: Visual acuity change from baseline.
Results: Statistically significant (P < 0.05) baseline predictors for less VA gain at year 2 were older age, VA of 20/40 or better, larger choroidal neovascularization area, presence of geographic atrophy, total foveal thickness <= 325 mu m or >= 425 mu m, and elevation of retinal pigment epithelium. Among 176 eyes gaining >= 3 lines at week 12, 78% had a >= 3-line gain at year 2, whereas among 113 eyes losing >= 1-line at week 12, 27% improved to a >= 1-line gain at year 2. Visual acuity response at week 12 was more predictive of VA response at year 2 (R-2 = 0.30) than VA response at week 4 (R-2 = 0.17) and baseline predictors (R-2 = 0.13; P < 0.0001). Among 126 candidates for changing treatment drug at week 12, mean VA improved by 2.8 letters (P = 0.050), mean total retinal thickness decreased 53 mu m (P < 0.0001), and fluid resolved in 33% (P < 0.0001) between week 12 and year 1 with continued use of the same drug and regimen. Similar improvements were observed among 83 candidates for changing drugs at week 24.
Conclusions: Visual acuity response at week 12 is more predictive of 2-year vision outcomes than either several baseline characteristics or week 4 response. Eyes with poor initial response may benefit from continued treatment without switching to another drug. Ophthalmology 2015; 122:2523-2531 (C) 2015 by the American Academy of Ophthalmology.
C1 [Ying, Gui-shuang; Maguire, Maureen G.; Daniel, Ebenezer; Grunwald, Juan E.; Huang, Jiayan] Univ Penn, Dept Ophthalmol, Philadelphia, PA 19104 USA.
[Ferris, Frederick L.] NEI, NIH, Bethesda, MD 20892 USA.
[Jaffe, Glenn J.; Toth, Cynthia A.] Duke Univ, Dept Ophthalmol, Durham, NC USA.
[Martin, Daniel F.] Cleveland Clin, Cole Eye Inst, Cleveland, OH 44106 USA.
RP Ying, GS (reprint author), Univ Penn, Dept Ophthalmol, 3535 Market St,Suite 700, Philadelphia, PA 19104 USA.
EM gsying@mail.med.upenn.edu
OI Grunwald, Juan/0000-0002-5973-6616; Maguire, Maureen/0000-0002-4249-2467
FU Bioptigen (Morrisville, NC); Genentech (San Francisco, CA); Physical
Sciences Inc (Andover, MA); Consultant - Alcon Laboratories (Fort Worth,
TX); Thrombogenics (Iselin, NJ); Consultant - Genentech (San Francisco,
CA); National Eye Institute, National Institutes of Health, Bethesda,
Maryland [U10 EY017823, U10 EY017825, U10 EY017826, U10 EY017828,
R21EY023689]
FX The author(s) have no proprietary or commercial interest in any
materials discussed in this article. G.-S. Y.: Consultant -Janssen
(Titusville, NJ) C.A.T.: Financial Support - Bioptigen (Morrisville,
NC), Genentech (San Francisco, CA), Physical Sciences Inc (Andover,
MA).; Consultant - Alcon Laboratories (Fort Worth, TX), Thrombogenics
(Iselin, NJ) M.G.M.: Consultant - Genentech (San Francisco, CA);
Supported by the National Eye Institute, National Institutes of Health,
Bethesda, Maryland (cooperative agreement nos.: U10 EY017823, U10
EY017825, U10 EY017826, U10 EY017828, and R21EY023689).
NR 25
TC 6
Z9 7
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0161-6420
EI 1549-4713
J9 OPHTHALMOLOGY
JI Ophthalmology
PD DEC
PY 2015
VL 122
IS 12
BP 2523
EP +
DI 10.1016/j.ophtha.2015.08.015
PG 10
WC Ophthalmology
SC Ophthalmology
GA CZ4EZ
UT WOS:000367057500032
PM 26383996
ER
PT J
AU Swineford, LB
Guthrie, W
Thurm, A
AF Swineford, Lauren B.
Guthrie, Whitney
Thurm, Audrey
TI Convergent and Divergent Validity of the Mullen Scales of Early Learning
in Young Children With and Without Autism Spectrum Disorder
SO PSYCHOLOGICAL ASSESSMENT
LA English
DT Article
DE factor structure; Mullen Scales of Early Learning; validity; autism
spectrum disorder
ID CONFIRMATORY FACTOR-ANALYSIS; OF-FIT INDEXES; MEASUREMENT INVARIANCE;
WISC-IV; INTELLIGENCE; BEHAVIOR; MODELS; SCORES; SAMPLE
AB The purpose of this study was to report on the construct, convergent, and divergent validity of the Mullen Scales of Early Learning (MSEL), a widely used test of development for young children. The sample consisted of 399 children with a mean age of 3.38 years (SD = 1.14) divided into a group of children with autism spectrum disorder (ASD) and a group of children not on the autism spectrum, with and without developmental delays. The study used the MSEL and several other measures assessing constructs relevant to the age range including developmental skills, autism symptoms, and psychopathology symptoms across multiple methods of assessment. Multiple group confirmatory factor analyses revealed good overall fit and equal form of the MSEL 1-factor model across the ASD and nonspectnnu 2roups, supporting the construct validity of the MSEL. However, neither full nor partial invariance of factor loadings was established because of the lower loadings in the, ASD group compared with the, nonspectrum 2roup. Exploratory structural equation modeling revealed that other measures of developmental skills loaded together with the MSEL domain scores on a Developmental Functioning factor, supporting convergent validity of the MSEL. Divergent validity- was supported by- the lack of loading of MSEL domain scores on Autism Symptoms or Emotion/Behavior Problems factors. Although factor structure, and loadings V a ri d across groups, Convergent and divergent V alidity findings were, similar in the ASD and nonspectrum samples. Together, these results demonstrate evidence for the construct, convergent, and divergent validity of the MSEL using powerful data analytic techniques.
C1 [Swineford, Lauren B.; Thurm, Audrey] NIMH, Pediat & Dev Neurosci Branch, Bethesda, MD 20892 USA.
[Guthrie, Whitney] Florida State Univ, Dept Psychol, Tallahassee, FL 32306 USA.
RP Swineford, LB (reprint author), NIMH, Pediat & Dev Neurosci Branch, 10 Ctr Dr MSC 1255,Bldg 10,Room 1C250, Bethesda, MD 20892 USA.
EM swinefordlb@mail.nih.gov
FU National Institute of Mental Health [NCT00271622, 06-M-0065]
FX This research was supported by the Intramural Program of the National
Institute of Mental Health, NCT00271622, 06-M-0065. Selected results
were presented at the Society for Research on Child Development in
Seattle, Washington, March 2013.
NR 56
TC 1
Z9 1
U1 2
U2 10
PU AMER PSYCHOLOGICAL ASSOC
PI WASHINGTON
PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA
SN 1040-3590
EI 1939-134X
J9 PSYCHOL ASSESSMENT
JI Psychol. Assess.
PD DEC
PY 2015
VL 27
IS 4
BP 1364
EP 1378
DI 10.1037/pas0000116
PG 15
WC Psychology, Clinical
SC Psychology
GA CZ0UG
UT WOS:000366820900022
PM 25894712
ER
PT J
AU Melo, DR
Brill, AB
Zanzonico, P
Vicini, P
Moroz, B
Kwon, D
Lamart, S
Brenner, A
Bouville, A
Simon, SL
AF Melo, Dunstana R.
Brill, Aaron B.
Zanzonico, Pat
Vicini, Paolo
Moroz, Brian
Kwon, Deukwoo
Lamart, Stephanie
Brenner, Alina
Bouville, Andre
Simon, Steven L.
TI Organ Dose Estimates for Hyperthyroid Patients Treated with I-131: An
Update of the Thyrotoxicosis Follow-Up Study
SO RADIATION RESEARCH
LA English
DT Article
ID THYROXINE DISTRIBUTION; RADIATION-DOSIMETRY; NUCLEAR-MEDICINE;
THYROID-CANCER; THERAPY; IODINE; EMPHASIS; SYSTEMS; FETUS
AB The Thyrotoxicosis Therapy Follow-up Study (TTFUS) is comprised of 35,593 hyperthyroid patients treated from the mid-1940s through the mid-1960s. One objective of the TTFUS was to evaluate the long-term effects of high-dose iodine-131 (I-131) treatment (1-4). In the TTFUS cohort, 23,020 patients were treated with I-131, including 21,536 patients with Graves disease (GD), 1,203 patients with toxic nodular goiter (TNG) and 281 patients with unknown disease. The study population constituted the largest group of hyperthyroid patients ever examined in a single health risk study. The average number (+/- 1 standard deviation) of I-131 treatments per patient was 1.7 +/- 1.4 for the GD patients and 2.1 +/- 2.1 for the TNG patients. The average total I-131 administered activity was 380 +/- 360 MBq for GD patients and 640 +/- 550 MBq for TNG patients. In this work, a biokinetic model for iodine was developed to derive organ residence times and to reconstruct the radiation-absorbed doses to the thyroid gland and to other organs resulting from administration of I-131 to hyperthyroid patients. Based on I-131 data for a small, kinetically well-characterized sub-cohort of patients, multivariate regression equations were developed to relate the numbers of disintegrations of I-131 in more than 50 organs and tissues to anatomical (thyroid mass) and clinical (percentage thyroid uptake and pulse rate) parameters. These equations were then applied to estimate the numbers of I-131 disintegrations in the organs and tissues of all other hyperthyroid patients in the TTFUS who were treated with I-131. The reference voxel phantoms adopted by the International Commission on Radiological Protection (ICRP) were then used to calculate the absorbed doses in more than 20 organs and tissues of the body. As expected, the absorbed doses were found to be highest in the thyroid (arithmetic means of 120 and 140 Gy for GD and TNG patients, respectively). Absorbed doses in organs other than the thyroid were much smaller, with arithmetic means of 1.6 Gy, 1.5 Gy and 0.65 Gy for esophagus, thymus and salivary glands, respectively. The arithmetic mean doses to all other organs and tissues were more than 100 times less than those to the thyroid gland. To our knowledge, this work represents the most comprehensive study to date of the doses received by persons treated with I-131 for hyperthyroidism. (C) 2015 by Radiation Research Society
C1 [Melo, Dunstana R.; Moroz, Brian; Lamart, Stephanie; Bouville, Andre; Simon, Steven L.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Brill, Aaron B.] Vanderbilt Univ, Nashville, TN 37232 USA.
[Zanzonico, Pat] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
[Vicini, Paolo] Univ Washington, Dept Bioengn, Seattle, WA 98195 USA.
[Kwon, Deukwoo; Brenner, Alina] Univ Miami, Sylvester Comprehens Canc Ctr, Miami, FL 33136 USA.
[Bouville, Andre] NCI, Bethesda, MD 20892 USA.
RP Melo, DR (reprint author), Lovelace Resp Res Inst, Ctr Countermeasures Radiat, 2425 Ridgecrest Dr SE, Albuquerque, NM 87108 USA.
EM dmelo@lrri.org
FU National Institute of Allergy and Infectious Diseases; National Cancer
Institute (NIAID) [Y2-A1-5077, Y3-CO-5117]; NCI Intramural Research
Program
FX This work was supported by the Intra-agency agreement between the
National Institute of Allergy and Infectious Diseases and the National
Cancer Institute (NIAID agreement no. Y2-A1-5077 and NCI agreement no.
Y3-CO-5117) and the NCI Intramural Research Program. The authors thank
Dr. Michael Stabin of Vanderbilt University for review of early versions
of the biokinetic model, Dr. Choonsik Lee of the National Cancer
Institute for assisting with calculation of S values and Dr. Elaine Ron
(deceased) for her vision and commitment to reanalyze the TTFUS
dosimetry and health risks, which ultimately resulted in this analysis.
NR 45
TC 1
Z9 1
U1 0
U2 2
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 DEC
PY 2015
VL 184
IS 6
BP 595
EP 610
DI 10.1667/RR14160.1
PG 16
WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging
SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology,
Nuclear Medicine & Medical Imaging
GA CZ5RW
UT WOS:000367160700006
PM 26579944
ER
PT J
AU Mansfield, AS
Tafur, AJ
Vulih, D
Smith, GL
Harris, PJ
Ivy, SP
AF Mansfield, A. S.
Tafur, A. J.
Vulih, D.
Smith, G. L.
Harris, P. J.
Ivy, S. P.
TI Severe hepatic dysfunction is associated with venous thromboembolic
events in phase 1 clinical trials
SO THROMBOSIS RESEARCH
LA English
DT Article
DE Clinical trials, phase 1; Liver diseases; Neoplasms; Pulmonary embolism;
Venous thrombosis
ID DEEP-VEIN THROMBOSIS; CANCER-PATIENTS; PULMONARY-EMBOLISM;
LIVER-DISEASES; RISK-FACTORS; CHEMOTHERAPY; SCORE; EPIDEMIOLOGY;
METAANALYSIS; MORTALITY
AB Introduction: Venous thromboembolic events (VTEs) are a significant cause of death in patients with cancer. The incidence of VTE is not well characterized in early phase clinical trials of novel antineoplastic agents, or in hepatic dysfunction studies designed for patients with varying degrees of liver test abnormalities. We compared the incidences of VTE in phase 1 clinical trials (P1CTs) and hepatic dysfunction trials (HDCTs) sponsored by the Cancer Therapy Evaluation Program of the National Cancer Institute (NCI) of the United States.
Materials & methods: We reviewed individual patient records of 1841 subjects for symptomatic VTE diagnosed while on study: 1328 subjects on 42 P1CTs, and 513 subjects on 9 HDCTs. The NCI's Organ Dysfunction Working Group definitions were used to categorize patients. The incidences of VTEs between patients were compared by the Chi square test. Confounders were evaluated with the Cochran-Mantel-Haenszel method.
Results & conclusions: There were 43 VTEs identified among all subjects (2.3%). There were significantly more VTE observed in the subjects on P1CTs (n = 38, 2.9%) than in the subjects on HDCTs (n = 5, 1.0%; RR 0.341, 95% 0.13-0.86, p = 0.015). For patients on HDCTs, those with severe dysfunction had a high incidence of VTE (RR 10.5 (1.12-93.6), p = 0.021) that remained significant in a multivariate model.
VTEs were observed less frequently in patients who were enrolled in HDCT than those who were enrolled in P1CT; however, patients with severe hepatic dysfunction were more likely to experience VTE. Severe liver test abnormalities may not be protective against VTE in patients with malignancies receiving chemotherapy. (C) 2015 Elsevier Ltd. All rights reserved.
C1 [Mansfield, A. S.] Mayo Clin, Div Med Oncol, Rochester, MN 55905 USA.
[Tafur, A. J.] Northshore Univ Hlth Syst, Vasc Med, Evanston, IL 60201 USA.
[Vulih, D.] Theradex, Princeton, NJ 08540 USA.
[Smith, G. L.] NCI, Clin Trials Monitoring Branch, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
[Harris, P. J.; Ivy, S. P.] NCI, Invest Drug Branch, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
RP Mansfield, AS (reprint author), Mayo Clin, Div Med Oncol, 200 First St SW, Rochester, MN 55905 USA.
EM mansfield.aaron@mayo.edu; atafur@northshore.org; DVulih@theradex.com;
SmithG@ctep.nci.nih.gov; harrispj@mail.nih.gov; ivyp@ctep.nci.nih.gov
OI Mansfield, Aaron/0000-0002-9483-6903
FU National Cancer Institutes of Health [K12CA090628]
FX This work was support in part by the National Cancer Institutes of
Health [K12CA090628 to A.S.M.].
NR 19
TC 0
Z9 0
U1 0
U2 2
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0049-3848
J9 THROMB RES
JI Thromb. Res.
PD DEC
PY 2015
VL 136
IS 6
BP 1169
EP 1173
DI 10.1016/j.thromres.2015.10.024
PG 5
WC Hematology; Peripheral Vascular Disease
SC Hematology; Cardiovascular System & Cardiology
GA CY9FM
UT WOS:000366712800024
PM 26493604
ER
PT J
AU Patel, D
Kitahara, CM
Park, Y
Liao, LM
Linet, M
Kebebew, E
Nilubol, N
AF Patel, Dhaval
Kitahara, Cari M.
Park, Yikyung
Liao, Linda M.
Linet, Martha
Kebebew, Electron
Nilubol, Naris
TI Thyroid Cancer and Nonsteroidal Anti-Inflammatory Drug Use: A Pooled
Analysis of Patients Older Than 40 Years of Age
SO THYROID
LA English
DT Article
ID CYCLOOXYGENASE-2 EXPRESSION; RADIOLOGIC TECHNOLOGISTS; PAPILLARY
CARCINOMA; UNITED-STATES; COX-2; METAANALYSIS; ASSOCIATION; HEALTH;
ASPIRIN; IMPACT
AB Background: Cyclooxygenase (COX-2) has been associated with tumor growth and metastasis in several cancers, including thyroid cancer. For this reason, several investigators have studied COX-2 inhibitors in preclinical models of thyroid cancer and found antineoplastic effects. Thus, the primary aim of this study was to assess if the use of nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with a reduced incidence of thyroid cancer. A second aim of the study was to determine additional risk or protective factors for thyroid cancer. Methods: Three large prospective population-based studies (the NIH-AARP Diet and Health Study; the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial; and the U.S. Radiologic Technologists Study) were pooled to investigate the association between self-reported frequency of aspirin and nonaspirin NSAID use one year prior to baseline (no use, 2/week, >2-6/week, and 7/week) and subsequent risk of thyroid cancer. A Cox regression proportional hazard model was used to estimate aggregated hazard ratios (HR) adjusted for cohort, sex, race/ethnicity, weight, smoking status, and alcohol intake. Results: There were 388,577 participants in the pooled cohort, with 481 cases of thyroid cancer. No significant risk reduction was observed with regular use of nonaspirin NSAIDs (HR=1.14 [confidence interval (CI) 0.84-1.55]), and/or regular use of aspirin (HR=1.06 [CI 0.82-1.39]). The multivariate regression analysis confirmed as previously reported in the literature that female sex, obesity class I (body mass index [BMI]=30-34.99kg/m(2)), and obesity class II (BMI=35-35.99kg/m(2)) were independently associated with an increased thyroid cancer risk. Current smoking status and moderate and excessive alcohol use were also confirmed as independent risk factors associated with a reduced thyroid cancer risk. Conclusions: Neither nonaspirin NSAIDs nor aspirin use is associated with a reduced risk of thyroid cancer. Women and obesity are associated with an increased risk of thyroid cancer, whereas smoking and alcohol use are associated with decreased risk of thyroid cancer.
C1 [Patel, Dhaval; Kebebew, Electron; Nilubol, Naris] NCI, Endocrine Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Kitahara, Cari M.] NCI, Div Canc Epidemiol & Genet, Radiat Epidemiol Branch, NIH, Bethesda, MD 20892 USA.
[Park, Yikyung; Liao, Linda M.; Linet, Martha] NCI, Div Canc Epidemiol & Genet, Nutr Epidemiol Branch, NIH, Bethesda, MD 20892 USA.
[Park, Yikyung] Washington Univ, Sch Med, Div Publ Hlth Sci, St Louis, MO USA.
RP Nilubol, N (reprint author), NCI, Endocrine Oncol Branch, NIH, Clin Res Ctr, Bldg 10-CRC,Room 3-5840, Bethesda, MD 20892 USA.
EM naris.nilubol@nih.gov
RI Kitahara, Cari/R-8267-2016;
OI Liao, Linda/0000-0002-1923-5294; Patel, Dhaval/0000-0002-5744-568X
FU Intramural Research Program of the NIH, National Cancer Institute
FX The authors would like to acknowledge the staff and data managers who
have worked to establish the PLCO, NIH-AARP, and USRT databases. The
authors would like to acknowledge David Venzon for his statistical
assistance. We are indebted to the participants in the NIH-AARP Diet and
Health Study for their outstanding cooperation. We also thank Sigurd
Hermansen and Kerry Grace Morrissey from Westat for study outcomes
ascertainment and management and Leslie Carroll at Information
Management Services for data support and analysis. This research was
supported in part by the Intramural Research Program of the NIH,
National Cancer Institute.
NR 32
TC 1
Z9 1
U1 1
U2 3
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1050-7256
EI 1557-9077
J9 THYROID
JI Thyroid
PD DEC 1
PY 2015
VL 25
IS 12
BP 1355
EP 1362
DI 10.1089/thy.2015.0198
PG 8
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA CY9CI
UT WOS:000366704600012
PM 26426828
ER
PT J
AU Webster, AF
Zumbo, P
Fostel, J
Gandara, J
Hester, SD
Recio, L
Williams, A
Wood, CE
Yauk, CL
Mason, CE
AF Webster, A. Francina
Zumbo, Paul
Fostel, Jennifer
Gandara, Jorge
Hester, Susan D.
Recio, Leslie
Williams, Andrew
Wood, Charles E.
Yauk, Carole L.
Mason, Christopher E.
TI Mining the Archives: A Cross-Platform Analysis of Gene Expression
Profiles in Archival Formalin-Fixed Paraffin-Embedded Tissues
SO TOXICOLOGICAL SCIENCES
LA English
DT Article
DE RNA-seq; microarray; toxicogenomics; FFPE; archival RNA; biorepositories
ID FEMALE B6C3F1 MICE; RNA-SEQ; RISK-ASSESSMENT; DIFFERENTIAL EXPRESSION;
SYSTEMATIC VARIATION; CELL-PROLIFERATION; CARCINOGEN FURAN; MICROARRAY
DATA; QUALITY-CONTROL; LINEAR-MODEL
AB Formalin-fixed paraffin-embedded (FFPE) tissue samples represent a potentially invaluable resource for transcriptomic research. However, use of FFPE samples in genomic studies has been limited by technical challenges resulting from nucleic acid degradation. Here we evaluated gene expression profiles derived from fresh-frozen (FRO) and FFPE mouse liver tissues preserved in formalin for different amounts of time using 2 DNA microarray protocols and 2 whole-transcriptome sequencing (RNA-seq) library preparation methodologies. The ribo-depletion protocol outperformed the other methods by having the highest correlations of differentially expressed genes (DEGs), and best overlap of pathways, between FRO and FFPE groups. The effect of sample time in formalin (18 h or 3 weeks) on gene expression profiles indicated that test article treatment, not preservation method, was the main driver of gene expression profiles. Meta- and pathway analyses indicated that biological responses were generally consistent for 18 h and 3 week FFPE samples compared with FRO samples. However, clear erosion of signal intensity with time in formalin was evident, and DEG numbers differed by platform and preservation method. Lastly, we investigated the effect of time in paraffin on genomic profiles. Ribo-depletion RNA-seq analysis of 8-, 19-, and 26-year-old control blocks resulted in comparable quality metrics, including expected distributions of mapped reads to exonic, untranslated region, intronic, and ribosomal fractions of the transcriptome. Overall, our results indicate that FFPE samples are appropriate for use in genomic studies in which frozen samples are not available, and that ribo-depletion RNA-seq is the preferred method for this type of analysis in archival and long-aged FFPE samples.
C1 [Webster, A. Francina; Williams, Andrew; Yauk, Carole L.] Hlth Canada, Environm Hlth Sci & Res Bur, Ottawa, ON K1A 0K9, Canada.
[Webster, A. Francina] Carleton Univ, Dept Biol, Ottawa, ON K1S 5B6, Canada.
[Zumbo, Paul; Gandara, Jorge; Mason, Christopher E.] Weill Cornell Med Coll, Dept Physiol & Biophys, New York, NY 10065 USA.
[Fostel, Jennifer] NIEHS, Res Triangle Pk, NC 27709 USA.
[Hester, Susan D.; Wood, Charles E.] US EPA, Off Res & Dev, Res Triangle Pk, NC 27709 USA.
[Recio, Leslie] ILS Inc, Res Triangle Pk, NC 27709 USA.
[Mason, Christopher E.] Feil Family Brain & Mind Res Inst BMRI, New York, NY 10021 USA.
[Mason, Christopher E.] HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsau, New York, NY 10065 USA.
RP Yauk, CL (reprint author), Hlth Canada, HECSB, ERHSD, Environm Hlth Sci & Res Bur, Bldg 8,P-L 0803A,50 Colombine Driveway, Ottawa, ON K1A 0K9, Canada.
EM Carole.Yauk@hc-sc.gc.ca; chm2042@med.cornell.edu
FU NTP [NO1-ES-55536]
FX We thank the ILS animal care group for performing the furan mouse
exposures and fixing these tissues, and the NTP contract NO1-ES-55536
for preparing the archival RNA. The authors greatly acknowledge Weill
Cornell Epigenomics Core contribution and technical support from
Jennifer A. Busuttil and Caroline Sheridan. We also thank the Bert L.
and N. Kuggie Vallee Foundation Young Investigator Award and the
WorldQuant Foundation. The authors also acknowledge Dr. Matt Meier and
Dr Ivy Moffat for helpful comments on the article.
NR 48
TC 4
Z9 4
U1 2
U2 8
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 DEC
PY 2015
VL 148
IS 2
BP 460
EP 472
DI 10.1093/toxsci/kfv195
PG 13
WC Toxicology
SC Toxicology
GA CZ6FB
UT WOS:000367195500011
PM 26361796
ER
PT J
AU Howdeshell, KL
Rider, CV
Wilson, VS
Furr, JR
Lambright, CR
Gray, LE
AF Howdeshell, Kembra L.
Rider, Cynthia V.
Wilson, Vickie S.
Furr, Johnathan R.
Lambright, Christy R.
Gray, L. Earl, Jr.
TI Dose Addition Models Based on Biologically Relevant Reductions in Fetal
Testosterone Accurately Predict Postnatal Reproductive Tract Alterations
by a Phthalate Mixture in Rats
SO TOXICOLOGICAL SCIENCES
LA English
DT Article
DE dose addition; phthalates; postnatal developmental toxicity; male
reproductive tract; endocrine disruptors; mixture models
ID N-BUTYL PHTHALATE; ALTERS SEXUAL-DIFFERENTIATION; CUMULATIVE
RISK-ASSESSMENT; SPRAGUE-DAWLEY RATS; IN-UTERO EXPOSURE; DI(N-BUTYL)
PHTHALATE; BENZYL PHTHALATE; GENE-EXPRESSION; DIETHYLHEXYL PHTHALATE;
DEVELOPMENTAL TOXICITY
AB Challenges in cumulative risk assessment of anti-androgenic phthalate mixtures include a lack of data on all the individual phthalates and difficulty determining the biological relevance of reduction in fetal testosterone (T) on postnatal development. The objectives of the current study were 2-fold: (1) to test whether a mixture model of dose addition based on the fetal T production data of individual phthalates would predict the effects of a 5 phthalate mixture on androgen-sensitive postnatal male reproductive tract development, and (2) to determine the biological relevance of the reductions in fetal T to induce abnormal postnatal reproductive tract development using data from the mixture study. We administered a dose range of the mixture (60, 40, 20, 10, and 5% of the top dose used in the previous fetal T production study consisting of 300 mg/kg per chemical of benzyl butyl (BBP), di(n)butyl (DBP), diethyl hexyl phthalate (DEHP), di-isobutyl phthalate (DiBP), and 100 mg dipentyl (DPP) phthalate/kg; the individual phthalates were present in equipotent doses based on their ability to reduce fetal T production) via gavage to Sprague Dawley rat dams on GD8-postnatal day 3. We compared observed mixture responses to predictions of dose addition based on the previously published potencies of the individual phthalates to reduce fetal T production relative to a reference chemical and published postnatal data for the reference chemical (called DA(ref)). In addition, we predicted DA (called DA(all)) and response addition (RA) based on logistic regression analysis of all 5 individual phthalates when complete data were available. DA (ref) and DA (all) accurately predicted the observed mixture effect for 11 of 14 endpoints. Furthermore, reproductive tract malformations were seen in 17-100% of F1 males when fetal T production was reduced by about 25-72%, respectively.
C1 [Howdeshell, Kembra L.; Rider, Cynthia V.] NIEHS, Div Natl Toxicol Program NTP, Res Triangle Pk, NC 27709 USA.
[Wilson, Vickie S.; Furr, Johnathan R.; Lambright, Christy R.; Gray, L. Earl, Jr.] US EPA, Off Res & Dev, Natl Hlth & Environm Effects Res Labs, Toxicol Assessment Div TAD,Reprod Toxicol Branch, Res Triangle Pk, NC 27711 USA.
RP Howdeshell, KL (reprint author), NIEHS, Div Natl Toxicol Program NTP, POB 12233, Res Triangle Pk, NC 27709 USA.
EM howdeshellkl@niehs.nih.gov
OI Wilson, Vickie/0000-0003-1661-8481
FU NIH, National Institute of Environmental Health Sciences
FX We wish to thank Dr Eve Mylchreest for providing us the original data
from her 1998 DBP study (Mylchreest et al., 1998). We thank Mary Cardon
and Dr Phillip Hartig for their help in fetal necropsies, Dr Dieldrich
Bermudez for his assistance with adult necropsies, and Dr Donald A.
Smith for his mathematical advice. This work was supported in part by
the NIH, National Institute of Environmental Health Sciences. This
research described in this article has been reviewed by the National
Health and Environmental Effects Research Laboratory, U.S. EPA, and has
been approved for publication. Approval does not necessarily reflect the
views and policies of the U.S. EPA nor does mention of trade names or
commercial products constitute endorsement or recommendation for use.
NR 50
TC 5
Z9 5
U1 7
U2 14
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 DEC
PY 2015
VL 148
IS 2
BP 488
EP 502
DI 10.1093/toxsci/kfv196
PG 15
WC Toxicology
SC Toxicology
GA CZ6FB
UT WOS:000367195500013
PM 26350170
ER
PT J
AU Suffredini, DA
Sampath-Kumar, H
Li, Y
Ohanjanian, L
Remy, KE
Cui, XZ
Eichacker, PQ
AF Suffredini, Dante A.
Sampath-Kumar, Hanish
Li, Yan
Ohanjanian, Lernik
Remy, Kenneth E.
Cui, Xizhong
Eichacker, Peter Q.
TI Does Bacillus anthracis Lethal Toxin Directly Depress Myocardial
Function? A Review of Clinical Cases and Preclinical Studies
SO TOXINS
LA English
DT Review
DE Bacillus anthracis; anthrax; lethal and edema toxins; cardiovascular
dysfunction; shock; treatment
ID FATAL INHALATIONAL ANTHRAX; EDEMA TOXINS; SEPTIC SHOCK; UNITED-STATES;
SEVERE SEPSIS; HEROIN USERS; DYSFUNCTION; BIOTERRORISM; PATHOLOGY; RATS
AB The US outbreak of B.anthracis infection in 2001 and subsequent cases in the US and Europe demonstrate that anthrax is a continuing risk for the developed world. While several bacterial components contribute to the pathogenesis of B. anthracis, production of lethal toxin (LT) is strongly associated with the development of hypotension and lethality. However, the mechanisms underlying the cardiovascular instability LT produces are unclear. Some evidence suggests that LT causes shock by impairing the peripheral vasculature, effects consistent with the substantial extravasation of fluid in patients dying with B. anthracis. Other data suggests that LT directly depresses myocardial function. However a clinical correlate for this latter possibility is less evident since functional studies and post-mortem examination in patients demonstrate absent or minimal cardiac changes. The purposes of this review were to first present clinical studies of cardiac functional and histologic pathology with B. anthracis infection and to then examine in vivo, in vitro, and ex vivo preclinical studies of LT's myocardial effects. Together, these data suggest that it is unclear whether that LT directly depresses cardiac function. This question is important for the clinical management and development of new therapies for anthrax and efforts should continue to be made to answer it.
C1 [Suffredini, Dante A.; Sampath-Kumar, Hanish; Li, Yan; Ohanjanian, Lernik; Cui, Xizhong; Eichacker, Peter Q.] NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA.
[Remy, Kenneth E.] Washington Univ, Sch Med, Dept Pediat, Div Crit Care Med, St Louis, MO 63110 USA.
RP Suffredini, DA (reprint author), NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA.
EM dante.suffredini@nih.gov; hanishsampathkumar@gmail.com; yli3@cc.nih.gov;
lernik.ohanjanian@nih.gov; Remy_K@kids.wustl.edu; CXizhong@cc.nih.gov;
PEichacker@cc.nih.gov
NR 61
TC 1
Z9 1
U1 1
U2 5
PU MDPI AG
PI BASEL
PA POSTFACH, CH-4005 BASEL, SWITZERLAND
SN 2072-6651
J9 TOXINS
JI Toxins
PD DEC
PY 2015
VL 7
IS 12
BP 5417
EP 5434
DI 10.3390/toxins7124891
PG 18
WC Toxicology
SC Toxicology
GA CZ3OI
UT WOS:000367013500040
PM 26703730
ER
PT J
AU Goldstein, I
Hager, GL
AF Goldstein, Ida
Hager, Gordon L.
TI Transcriptional and Chromatin Regulation during Fasting - The Genomic
Era
SO TRENDS IN ENDOCRINOLOGY AND METABOLISM
LA English
DT Review
ID GROWTH-FACTOR 21; THYROID-HORMONE RECEPTOR; FATTY-ACID OXIDATION;
HEPATIC GLUCONEOGENESIS; GLUCOCORTICOID-RECEPTOR; LIPID-METABOLISM;
PPAR-ALPHA; GLUCOSE-PRODUCTION; DIABETES-MELLITUS; NUCLEAR RECEPTORS
AB An elaborate metabolic response to fasting is orchestrated by the liver and is heavily reliant on transcriptional regulation. In response to hormones (glucagon, glucocorticoids) many transcription factors (TFs) are activated and regulate various genes involved in metabolic pathways aimed at restoring homeostasis: gluconeogenesis, fatty acid oxidation, ketogenesis, and amino acid shuttling. We summarize recent discoveries regarding fasting-related TFs with an emphasis on genome-wide binding patterns. Collectively, the findings we discuss reveal a large degree of cooperation between TFs during fasting that occurs at motif-rich DNA sites bound by a combination of TFs. These new findings implicate transcriptional and chromatin regulation as major determinants of the response to fasting and unravels the complex, multi-TF nature of this response.
C1 [Goldstein, Ida; Hager, Gordon L.] NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA.
RP Goldstein, I (reprint author), NCI, Lab Receptor Biol & Gene Express, NIH, Bethesda, MD 20892 USA.
EM goldstein.ido@gmail.com; hagerg@dce41.nci.nih.gov
OI Goldstein, Ido/0000-0003-0139-1499
FU Intramural NIH HHS [Z01 BC005450-24]
NR 96
TC 5
Z9 6
U1 0
U2 13
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 DEC
PY 2015
VL 26
IS 12
BP 699
EP 710
DI 10.1016/j.tem.2015.09.005
PG 12
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA CZ3TA
UT WOS:000367025700006
PM 26520657
ER
PT J
AU Germain, RN
Fowlkes, BJ
Samelson, LE
Leonard, WJ
AF Germain, Ronald N.
Fowlkes, B. J.
Samelson, Lawrence E.
Leonard, Warren J.
TI William E. Paul, MD (1936-2015) In Memoriam
SO TRENDS IN IMMUNOLOGY
LA English
DT Biographical-Item
C1 [Germain, Ronald N.] NIAID, Lab Syst Biol, NIH, Bethesda, MD 20892 USA.
[Fowlkes, B. J.] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA.
[Samelson, Lawrence E.] NCI, Cellular & Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
[Leonard, Warren J.] NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA.
[Leonard, Warren J.] NHLBI, Ctr Immunol, NIH, Bethesda, MD 20892 USA.
RP Germain, RN (reprint author), NIAID, Lab Syst Biol, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM rgermain@nlh.gov
NR 1
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1471-4906
EI 1471-4981
J9 TRENDS IMMUNOL
JI Trends Immunol.
PD DEC
PY 2015
VL 36
IS 12
BP 751
EP 753
DI 10.1016/j.it.2015.10.001
PG 3
WC Immunology
SC Immunology
GA CZ4ZD
UT WOS:000367110800001
PM 27064162
ER
PT J
AU Luciano, M
Marioni, RE
Hernandez, MV
Maniega, SM
Hamilton, IF
Royle, NA
Scotland, G
Chauhan, G
Bis, JC
Debette, S
DeCarli, C
Fornage, M
Schmidt, R
Ikram, MA
Launer, LJ
Seshadri, S
Bastin, ME
Porteous, DJ
Wardlaw, J
Deary, IJ
AF Luciano, Michelle
Marioni, Riccardo E.
Hernandez, Maria Valdes
Maniega, Susana Munoz
Hamilton, Iona F.
Royle, Natalie A.
Scotland, Generation
Chauhan, Ganesh
Bis, Joshua C.
Debette, Stephanie
DeCarli, Charles
Fornage, Myriam
Schmidt, Reinhold
Ikram, M. Arfan
Launer, Lenore J.
Seshadri, Sudha
Bastin, Mark E.
Porteous, David J.
Wardlaw, Joanna
Deary, Ian J.
CA CHARGE Consortium
TI Structural Brain MRI Trait Polygenic Score Prediction of Cognitive
Abilities
SO TWIN RESEARCH AND HUMAN GENETICS
LA English
DT Article
DE polygenic prediction; white matter hyperintensities; brain infarct;
intracranial volume; hippocampal volume; total brain volume; general
cognitive ability
ID GENOME-WIDE ASSOCIATION; INTRACRANIAL VOLUME; HIPPOCAMPAL VOLUME; HUMAN
INTELLIGENCE; COMMON VARIANTS; OLD-AGE; METAANALYSIS; INFARCTS;
INDIVIDUALS; DISEASE
AB Structural brain magnetic resonance imaging (MRI) traits share part of their genetic variance with cognitive traits. Here, we use genetic association results from large meta-analytic studies of genome-wide association (GWA) for brain infarcts (BI), white matter hyperintensities, intracranial, hippocampal, and total brain volumes to estimate polygenic scores for these traits in three Scottish samples: Generation Scotland: Scottish Family Health Study (GS:SFHS), and the Lothian Birth Cohorts of 1936 (LBC1936) and 1921 (LBC1921). These five brain MRI trait polygenic scores were then used to: (1) predict corresponding MRI traits in the LBC1936 (numbers ranged 573 to 630 across traits), and (2) predict cognitive traits in all three cohorts (in 8,115-8,250 persons). In the LBC1936, all MRI phenotypic traits were correlated with at least one cognitive measure, and polygenic prediction of MRI traits was observed for intracranial volume. Meta-analysis of the correlations between MRI polygenic scores and cognitive traits revealed a significant negative correlation (maximal r = 0.08) between the HV polygenic score and measures of global cognitive ability collected in childhood and in old age in the Lothian Birth Cohorts. The lack of association to a related general cognitive measure when including the GS:SFHS points to either type 1 error or the importance of using prediction samples that closely match the demographics of the GWA samples from which prediction is based. Ideally, these analyses should be repeated in larger samples with data on both MRI and cognition, and using MRI GWA results from even larger meta-analysis studies.
C1 [Luciano, Michelle; Marioni, Riccardo E.; Hernandez, Maria Valdes; Maniega, Susana Munoz; Hamilton, Iona F.; Royle, Natalie A.; Bastin, Mark E.; Porteous, David J.; Wardlaw, Joanna; Deary, Ian J.] Univ Edinburgh, Ctr Cognit Ageing & Cognit Epidemiol, Edinburgh EH8 9JZ, Midlothian, Scotland.
[Luciano, Michelle; Deary, Ian J.] Univ Edinburgh, Dept Psychol, Edinburgh EH8 9JZ, Midlothian, Scotland.
[Marioni, Riccardo E.; Scotland, Generation; Porteous, David J.] Univ Edinburgh, Inst Genet & Mol Med, Med Genet Sect, Ctr Genom & Expt Med, Edinburgh EH8 9JZ, Midlothian, Scotland.
[Marioni, Riccardo E.] Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia.
[Hernandez, Maria Valdes; Maniega, Susana Munoz; Hamilton, Iona F.; Royle, Natalie A.; Bastin, Mark E.; Wardlaw, Joanna] Univ Edinburgh, Brain Res Imaging Ctr, Edinburgh EH8 9JZ, Midlothian, Scotland.
[Hernandez, Maria Valdes; Hamilton, Iona F.; Royle, Natalie A.; Bastin, Mark E.; Wardlaw, Joanna] Univ Edinburgh, Ctr Clin Brain Sci, Edinburgh EH8 9JZ, Midlothian, Scotland.
[Hernandez, Maria Valdes; Maniega, Susana Munoz; Hamilton, Iona F.; Royle, Natalie A.; Bastin, Mark E.; Wardlaw, Joanna] Univ Edinburgh, Dept Neuroimaging Sci, SINAPSE, Edinburgh EH8 9JZ, Midlothian, Scotland.
[Chauhan, Ganesh; Debette, Stephanie] INSERM, Res Ctr Epidemiol & Biostat U897, Team Neuroepidemiol, Bordeaux, France.
[Chauhan, Ganesh; Debette, Stephanie] Univ Bordeaux, Bordeaux, France.
[Bis, Joshua C.] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.
[Bis, Joshua C.] Univ Washington, Dept Med, Seattle, WA USA.
[Debette, Stephanie; Seshadri, Sudha] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02215 USA.
[Debette, Stephanie] Bordeaux Univ Hosp, Dept Neurol, Bordeaux, France.
[DeCarli, Charles] Univ Calif Davis, Dept Neurol, Davis, CA 95616 USA.
[DeCarli, Charles] Univ Calif Davis, Ctr Neurosci, Davis, CA 95616 USA.
[Fornage, Myriam] Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Div Epidemiol, Brown Fdn Inst Mol Med, Houston, TX 77030 USA.
[Fornage, Myriam] Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Div Epidemiol, Ctr Human Genet, Houston, TX 77030 USA.
[Schmidt, Reinhold] Med Univ Graz, Dept Neurol, Graz, Austria.
[Ikram, M. Arfan] Eramus MC Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands.
[Ikram, M. Arfan] Eramus MC Univ, Med Ctr, Dept Radiol & Neurol, Rotterdam, Netherlands.
[Launer, Lenore J.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
[Seshadri, Sudha; CHARGE Consortium] Framingham Heart Dis Epidemiol Study, Framingham, MA USA.
RP Luciano, M (reprint author), Univ Edinburgh, Psychol, 7 George Sq, Edinburgh EH8 9JZ, Midlothian, Scotland.
EM michelle.luciano@ed.ac.uk
OI Seshadri, Sudha/0000-0001-6135-2622
FU Chief Scientist Office (CSO) of the Scottish Government Health
Directorates [CZD/16/6]; Scottish Funding Council [HR03006]; BBSRC; Age
UK's The Disconnected Mind project; UK's Biotechnology and Biological
Sciences Research Council (BBSRC); Medical Research Council; Scottish
Funding Council SINAPSE Collaboration; National Heart, Lung, and Blood
Institute (NHLBI) [HL105756]; National Institute on Ageing (NIA) [AG
033193]; ADCC [P30 010129]; NIA [N01-AG-12100, AG023629, R01AG15928,
R01AG20098, AG008122, AG033193]; NHLBI [HL105756, HHSN268201100005C,
HHSN268201100006C, HHSN268201100007C, HHSN268201100008C,
HHSN268201100009C, HHSN268201100010C, HHSN268201100011C,
HHSN268201100012C, R01HL087641, R01HL59367, R01HL086694, N01-HC-55015,
N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021,
N01-HC-55022, R01-HL087641, U01 HL096917, R01-HL093029,
HHSN268201200036C, HHSN268200800007C, N01HC55222, N01HC85079,
N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, HL080295,
HL087652, HL103612, HL068986, HL120393, HL093029, HL096917, NS087541];
National Human Genome Research Institute [U01HG004402]; NIH
[HHSN268200625226C]; National Institutes of Health [UL1RR025005]; ASPS:
The Austrian Science Fund (FWF) [P20545-P05, P13180]; National Center
for Advancing Translational Sciences, CTSI [UL1TR000124]; National
Institute of Diabetes and Digestive, and Kidney Disease Diabetes
Research Center (DRC) [DK063491]; NHLBI's Framingham Heart Study
[N01-HC-25195]; Affymetrix, Inc [N02-HL-6-4278]; NINDS [R01 NS17950];
Fondation pour la Recherche Medicale; Caisse Nationale Maladie des
Travailleurs Salaries; Direction Generale de la Sante; Mutuelle Generale
de l'Education Nationale (MGEN); Institut de la Longevite; Conseils
Regionaux of Aquitaine and Bourgogne; Fondation de France; Ministry of
Research-INSERM Programme 'Cohortes et collections de donnees
biologiques'; Eisai; National Foundation for Alzheimer's Disease and
Related Disorders; Institut Pasteur de Lille; Centre National de
Genotypage; Fondation Leducq; Erasmus Medical Center; Erasmus
University, Rotterdam; Netherlands Organization for the Health Research
and Development (ZonMw); Research Institute for Diseases in the Elderly
(RIDE); Ministry of Education, Culture and Science; Ministry for Health,
Welfare and Sports; European Commission; Municipality of Rotterdam; NIH
Roadmap for Medical Research
FX GS:SFHS has received core funding from the Chief Scientist Office (CSO)
of the Scottish Government Health Directorates CZD/16/6 and the Scottish
Funding Council HR03006. Phenotype collection in the LBC1921 was
supported by the BBSRC, The Royal Society, and the CSO of the Scottish
Government. LBC1936 phenotype collection was supported by Research Into
Ageing (now part of Age UK's The Disconnected Mind project). LBC
genotyping was supported by the UK's Biotechnology and Biological
Sciences Research Council (BBSRC). The work was undertaken by The
University of Edinburgh Centre for Cognitive Ageing and Cognitive
Epidemiology, part of the cross-council Life-long Health and Wellbeing
Initiative (MR/K026992/1), with funding from the BBSRC and Medical
Research Council. Imaging was performed in the Brain Research Imaging
Centre, Edinburgh, supported by the Scottish Funding Council SINAPSE
Collaboration.; Infrastructure for the CHARGE Consortium is supported in
part by the National Heart, Lung, and Blood Institute (NHLBI) grant
HL105756 and for the neurology working group of CHARGE (neuroCHARGE)
through a grant from the National Institute on Ageing (NIA), AG 033193.
CDC acknowledges support from ADCC grant P30 010129. AGES: Age, Gene,
Environment Susceptibility Reykjavik Study: This study has been funded
by NIA contract N01-AG-12100 with contributions from NEI, NIDCD, and
NHLBI, the NIA Intramural Research Program, Hjartavernd (the Icelandic
Heart Association), and the Althingi (the Icelandic Parliament). ARIC:
The Atherosclerosis Risk in Communities Study is carried out as a
collaborative study supported by NHLBI contracts (HHSN268201100005C,
HHSN268201100006C, HHSN268201100007C, HHSN268201100008C,
HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, and
HHSN268201100012C), R01HL087641, R01HL59367, and R01HL086694; National
Human Genome Research Institute contract U01HG004402; NIH contract
HHSN268200625226C, NHLBI contracts N01-HC-55015, N01-HC-55016,
N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021, N01-HC-55022,
and grants R01-HL087641, U01 HL096917, and R01-HL093029 (Fornage).
Infrastructure was partly supported by Grant Number UL1RR025005, a
component of the National Institutes of Health and NIH Roadmap for
Medical Research. ASPS: The Austrian Science Fund (FWF) grant number
P20545-P05 and P13180. The Medical University of Graz. CHS:
Cardiovascular Health Study: This CHS research was supported by NHLBI
contracts HHSN268201200036C, HHSN268200800007C, N01HC55222, N01HC85079,
N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086; and NHLBI
grants HL080295, HL087652, HL105756, HL103612, HL068986, and HL120393
with additional contribution from the National Institute of Neurological
Disorders and Stroke (NINDS). Additional support was provided through
AG023629, R01AG15928, and R01AG20098 from NIA. A full list of principal
CHS investigators and institutions can be found at CHS-NHLBI.org/. The
provision of genotyping data was supported in part by the National
Center for Advancing Translational Sciences, CTSI grant UL1TR000124, and
the National Institute of Diabetes and Digestive, and Kidney Disease
Diabetes Research Center (DRC) grant DK063491 to the Southern California
Diabetes Endocrinology Research Center. FHS: Framingham Heart Study:
This work was supported by the NHLBI's Framingham Heart Study (Contract
No. N01-HC-25195) and its contract with Affymetrix, Inc for genotyping
services (Contract No. N02-HL-6-4278). This study as also supported by
grants from the NIA: AG008122 and AG033193, the NINDS (R01 NS17950), and
the NHLBI (HL093029, HL096917, NS087541). Three City Study (3C): The 3C
Study is conducted under a partnership agreement between the Institut
National de la Sante et de la Recherche Medicale (INSERM), the Victor
Segalen-Bordeaux II University, and Sanofi-Aventis. The Fondation pour
la Recherche Medicale funded the preparation and initiation of the
study. The 3C Study is also supported by the Caisse Nationale Maladie
des Travailleurs Salaries, Direction Generale de la Sante, Mutuelle
Generale de l'Education Nationale (MGEN), Institut de la Longevite,
Conseils Regionaux of Aquitaine and Bourgogne, Fondation de France, and
Ministry of Research-INSERM Programme 'Cohortes et collections de
donnees biologiques'. Lille Genopole received an unconditional grant
from Eisai.; This work was supported by the National Foundation for
Alzheimer's Disease and Related Disorders, the Institut Pasteur de Lille
and the Centre National de Genotypage. Ganesh Chauhan is supported by a
grant from the Fondation Leducq. RS: The Rotterdam Study is funded by
Erasmus Medical Center and Erasmus University, Rotterdam, the
Netherlands Organization for the Health Research and Development
(ZonMw), the Research Institute for Diseases in the Elderly (RIDE), the
Ministry of Education, Culture and Science, the Ministry for Health,
Welfare and Sports, the European Commission (DG XII), and the
Municipality of Rotterdam.
NR 35
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PU CAMBRIDGE UNIV PRESS
PI NEW YORK
PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA
SN 1832-4274
EI 1839-2628
J9 TWIN RES HUM GENET
JI Twin Res. Hum. Genet.
PD DEC
PY 2015
VL 18
IS 6
BP 738
EP 745
DI 10.1017/thg.2015.71
PG 8
WC Genetics & Heredity; Obstetrics & Gynecology
SC Genetics & Heredity; Obstetrics & Gynecology
GA CZ5RF
UT WOS:000367159000013
PM 26427786
ER
PT J
AU Imbrogno, S
Mazza, R
Pugliese, C
Filice, M
Angelone, T
Loh, YP
Tota, B
Cerra, MC
AF Imbrogno, S.
Mazza, R.
Pugliese, C.
Filice, M.
Angelone, T.
Loh, Y. P.
Tota, B.
Cerra, M. C.
TI Myocardial actions of the chromogranin A-derived pyroglutaminated
serpinin in the goldfish (Carassius auratus) and in the frog (Rana
esculenta)
SO VASCULAR PHARMACOLOGY
LA English
DT Meeting Abstract
C1 [Imbrogno, S.; Mazza, R.; Pugliese, C.; Filice, M.; Angelone, T.; Tota, B.; Cerra, M. C.] Univ Calabria, Dept Biol Ecol & Earth Sci, I-87036 Arcavacata Di Rende, CS, Italy.
[Loh, Y. P.] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1537-1891
EI 1879-3649
J9 VASC PHARMACOL
JI Vasc. Pharmacol.
PD DEC
PY 2015
VL 75
BP 58
EP 59
DI 10.1016/j.vph.2015.11.080
PG 2
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA CZ3UH
UT WOS:000367029000052
ER
PT J
AU Rodenbach, KE
Schneider, MF
Furth, SL
Moxey-Mims, MM
Mitsnefes, MM
Weaver, DJ
Warady, BA
Schwartz, GJ
AF Rodenbach, Kyle E.
Schneider, Michael F.
Furth, Susan L.
Moxey-Mims, Marva M.
Mitsnefes, Mark M.
Weaver, Donald J.
Warady, Bradley A.
Schwartz, George J.
TI Hyperuricemia and Progression of CKD in Children and Adolescents: The
Chronic Kidney Disease in Children (CKiD) Cohort Study
SO AMERICAN JOURNAL OF KIDNEY DISEASES
LA English
DT Article
DE Uric acid; urate; hyperuricemia; risk factor; chronic kidney disease
(CKD); CKD progression; disease trajectory; pediatric kidney disease;
children; adolescents; CKiD (Chronic Kidney Disease in Children);
end-stage renal disease (ESRD); glomerular filtration rate (GFR); renal
replacement therapy (RRT); renal function decline
ID SERUM URIC-ACID; PEDIATRIC REFERENCE INTERVALS; BLOOD-PRESSURE;
ESSENTIAL-HYPERTENSION; BIOCHEMICAL ANALYTES; CARDIOVASCULAR RISK;
RENAL-DISEASE; FOLLOW-UP; ALLOPURINOL; HEALTHY
AB Background: Hyperuricemia is associated with essential hypertension in children. No previous studies have evaluated the effect of hyperuricemia on progression of chronic kidney disease (CKD) in children.
Study Design: Prospective observational cohort study.
Setting & Participants: Children and adolescents (n = 678 cross-sectional; n = 627 longitudinal) with a median age of 12.3 (IQR, 8.6-15.6) years enrolled at 52 North American sites of the CKiD (CKD in Children) Study.
Predictor: Serum uric acid level (<5.5, 5.5-7.5, and >7.5 mg/dL).
Outcomes: Composite end point of either >30% decline in glomerular filtration rate (GFR) or initiation of renal replacement therapy.
Measurements: Age, sex, race, blood pressure status, GFR, CKD cause, urine protein-creatinine ratio (<0.5, 0.5-<2.0, and >= 2.0 mg/mg), age- and sex-specific body mass index > 95th percentile, use of diuretics, and serum uric acid level.
Results: Older age, male sex, lower GFR, and body mass index. 95th percentile were associated with higher uric acid levels. 162, 294, and 171 participants had initial uric acid levels <5.5, 5.5 to >7.5, or.7.5 mg/dL, respectively. We observed 225 instances of the composite end point over 5 years. In a multivariable parametric time-to-event analysis, compared with participants with initial uric acid levels <5.5 mg/dL, those with uric acid levels of 5.5 to 7.5 or >7.5 mg/dL had 17% shorter (relative time, 0.83; 95% CI, 0.62-1.11) or 38% shorter (relative time, 0.62; 95% CI, 0.45-0.85) times to event, respectively. Hypertension, lower GFR, glomerular CKD cause, and elevated urine protein-creatinine ratio were also associated with faster times to the composite end point.
Limitations: The study lacked sufficient data to examine how use of specific medications might influence serum uric acid levels and CKD progression.
Conclusions: Hyperuricemia is a previously undescribed independent risk factor for faster progression of CKD in children and adolescents. It is possible that treatment of children and adolescents with CKD with urate-lowering therapy could slow disease progression. (C) 2015 by the National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.
C1 [Rodenbach, Kyle E.; Schwartz, George J.] Univ Rochester, Med Ctr, Rochester, NY 14642 USA.
[Schneider, Michael F.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Furth, Susan L.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
[Mitsnefes, Mark M.] NIDDK, Bethesda, MD 20892 USA.
[Mitsnefes, Mark M.] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45229 USA.
[Weaver, Donald J.] Levine Childrens Hosp, Charlotte, NC USA.
[Warady, Bradley A.] Childrens Mercy Hosp, Kansas City, MO 64108 USA.
RP Schwartz, GJ (reprint author), Univ Rochester, Box 777,Room 4-8105,601 Elmwood Ave, Rochester, NY 14642 USA.
EM george_schwartz@urmc.rochester.edu
FU NIDDK; National Institute of Neurological Disorders and Stroke; Eunice
Kennedy Shriver National Institute of Child Health and Human
Development; National Heart, Lung and Blood Institute [U01 DK82194,
U01-DK-66143, U01-DK-66174, U01-DK-66116]; Strong Children's Research
Center of the University of Rochester Department of Pediatrics
FX The CKiD Study is funded by the NIDDK, with additional funding from the
National Institute of Neurological Disorders and Stroke, the Eunice
Kennedy Shriver National Institute of Child Health and Human
Development, and the National Heart, Lung and Blood Institute (U01
DK82194, U01-DK-66143, U01-DK-66174, and U01-DK-66116). The NIDDK had a
role in the study design. Mr Rodenbach was also supported by the Strong
Children's Research Center of the University of Rochester Department of
Pediatrics for a summer fellowship in 2013, during which time he began
work on the uric acid project. GE Healthcare provided the Omnipaque
300T for the iohexol GFR studies, and Paula Maier performed
data entry.
NR 41
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U1 1
U2 4
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0272-6386
EI 1523-6838
J9 AM J KIDNEY DIS
JI Am. J. Kidney Dis.
PD DEC
PY 2015
VL 66
IS 6
BP 984
EP 992
DI 10.1053/j.ajkd.2015.06.015
PG 9
WC Urology & Nephrology
SC Urology & Nephrology
GA CZ0ZP
UT WOS:000366835700014
PM 26209544
ER
PT J
AU Paz-Soldan, VA
Morrison, AC
Lopez, JJC
Lenhart, A
Scott, TW
Elder, JP
Sihuincha, M
Kochel, TJ
Halsey, ES
Astete, H
McCall, PJ
AF Paz-Soldan, Valerie A.
Morrison, Amy C.
Cordova Lopez, Jhonny J.
Lenhart, Audrey
Scott, Thomas W.
Elder, John P.
Sihuincha, Moises
Kochel, Tadeusz J.
Halsey, Eric S.
Astete, Helvio
McCall, Philip J.
TI Dengue Knowledge and Preventive Practices in Iquitos, Peru
SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
LA English
DT Article
ID AEDES-AEGYPTI DIPTERA; CULICIDAE PRODUCTION; VIRUS TRANSMISSION;
CONTROLLED-TRIAL; CONTROL PROGRAM; VECTOR; URBAN; ACCEPTABILITY;
INTEREPIDEMIC; EPIDEMIOLOGY
AB As part of a cluster-randomized trial to evaluate insecticide-treated curtains for dengue prevention in Iquitos, Peru, we surveyed 1,333 study participants to examine knowledge and reported practices associated with dengue and its prevention. Entomological data from 1,133 of these households were linked to the survey. Most participants knew that dengue was transmitted by mosquito bite (85.6%), but only few (18.6%) knew that dengue vectors bite during daytime. Most commonly recognized dengue symptoms were fever (86.6%), headache (76.4%), and muscle/joint pain (67.9%). Most commonly reported correct practices for mosquito control were cleaning homes (61.6%), using insecticide sprays (23%), and avoiding having standing water at home (12.3%). Higher education was associated with higher knowledge about dengue, including transmission and vector control. Higher socioeconomic status was associated with increased reported use of preventive practices requiring money expenditure. We were less likely to find Aedes aegypti eggs, larvae, or pupae in households that had < 5-year-old children at home. Although dengue has been transmitted in Iquitos since the 1990s and the Regional Health Authority routinely fumigates households, treats domestic water containers with larvicide, and issues health education messages through mass media, knowledge of dengue transmission and household practices for prevention could be improved.
C1 [Paz-Soldan, Valerie A.] Tulane Univ, Sch Publ Hlth & Trop Med, Global Community Hlth & Behav Sci Dept, New Orleans, LA 70112 USA.
Univ Peruana Cayetano Heredia, Fac Salud Publ & Adm, Lima, Peru.
[Astete, Helvio] United States Naval Med Res Unit 6, Iquitos, Peru.
[Morrison, Amy C.; Scott, Thomas W.] Univ Calif Davis, Dept Entomol & Nematol, Davis, CA 95616 USA.
Univ Liverpool Liverpool Sch Trop Med, Iquitos, Peru.
[McCall, Philip J.] Univ Liverpool, Liverpool Sch Trop Med, Vector Biol Dept, Liverpool L3 5QA, Merseyside, England.
[Scott, Thomas W.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
San Diego State Univ, IBACH, San Diego, CA 92182 USA.
[Sihuincha, Moises] Hosp Apoyo, Dept Internal Med, Iquitos, Peru.
[Kochel, Tadeusz J.] Naval Med Res Ctr, Dept Virol, Silver Spring, MD USA.
Ctr Dis Control & Prevent, Malaria Branch, Atlanta, GA USA.
[Cordova Lopez, Jhonny J.] US Naval Med Res Ctr Detachment, Iquitos, Peru.
[Lenhart, Audrey] US Ctr Dis Control & Prevent, Entomol Branch, Div Parasit Dis & Malaria, Ctr Global Hlth, Atlanta, GA USA.
[Elder, John P.] San Diego State Univ, Sch Publ Hlth, San Diego, CA 92182 USA.
[Halsey, Eric S.] Ctr Dis Control & Prevent, Atlanta, GA USA.
RP Paz-Soldan, VA (reprint author), Tulane Univ, Sch Publ Hlth & Trop Med, Global Community Hlth & Behav Sci Dept, 1440 Canal St,Suite 2200, New Orleans, LA 70112 USA.
EM vpazsold@tulane.edu; amy.aegypti@gmail.com; jjcordova_2000@hotmail.com;
aj18@cdc.gov; twscott@ucdavis.edu; jelder@mail.sdsu.edu;
sihuincha@hotmail.com; Tadeusz.Kochel@nbacc.dhs.gov; ycw8@cdc.gov;
astetehelvio@gmail.com; philip.mccall@lstmed.ac.uk
FU Wellcome Trust [WT085714MA]; U.S. National Institutes of Health,
National Institute of Allergy and Infectious Diseases (NIH/MAID) [R01
AI069341-01]; NIH/NIAID [P01 AI098670]; Armed Forces Health Surveillance
Center Global Emerging Infections Systems Research Program
[847705.82000.25GB.B0016]; Military Infectious Disease Research Program
[S0263_10_LI, S0216_09_LI]; Fogarty International Center [K01
TW008414-01A1]; Research and Policy for Infectious Disease Dynamics
(RAPIDD) program of the Science and Technology Directorate, U.S.
Department of Homeland Security; Fogarty International Center, National
Institutes of Health
FX This research was supported by funding from the Wellcome Trust
(WT085714MA), the U.S. National Institutes of Health, National Institute
of Allergy and Infectious Diseases (NIH/MAID) award number R01
AI069341-01, the NIH/NIAID award number P01 AI098670, the Armed Forces
Health Surveillance Center Global Emerging Infections Systems Research
Program (847705.82000.25GB.B0016), and the Military Infectious Disease
Research Program (S0263_10_LI and S0216_09_LI). Valerie A. Paz-Soldan
received supported from the Fogarty International Center, award number
K01 TW008414-01A1. Thomas W. Scott received support from the Research
and Policy for Infectious Disease Dynamics (RAPIDD) program of the
Science and Technology Directorate, U.S. Department of Homeland
Security, and the Fogarty International Center, National Institutes of
Health.
NR 34
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U1 1
U2 9
PU AMER SOC TROP MED & HYGIENE
PI MCLEAN
PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA
SN 0002-9637
EI 1476-1645
J9 AM J TROP MED HYG
JI Am. J. Trop. Med. Hyg.
PD DEC
PY 2015
VL 93
IS 6
BP 1330
EP 1337
DI 10.4269/ajtmh.15-0096
PG 8
WC Public, Environmental & Occupational Health; Tropical Medicine
SC Public, Environmental & Occupational Health; Tropical Medicine
GA CY6TD
UT WOS:000366540800034
PM 26503276
ER
PT J
AU Goedeke, L
Rotllan, N
Ramirez, CM
Aranda, JF
Canfran-Duque, A
Araldi, E
Fernandez-Hernando, A
Langhi, C
de Cabo, R
Baldan, A
Suarez, Y
Fernandez-Hernando, C
AF Goedeke, Leigh
Rotllan, Noemi
Ramirez, Cristina M.
Aranda, Juan F.
Canfran-Duque, Alberto
Araldi, Elisa
Fernandez-Hernando, Ana
Langhi, Cedric
de Cabo, Rafael
Baldan, Angel
Suarez, Yajaira
Fernandez-Hernando, Carlos
TI miR-27b inhibits LDLR and ABCA1 expression but does not influence plasma
and hepatic lipid levels in mice
SO ATHEROSCLEROSIS
LA English
DT Article
DE miRNAs; miR-27b; LDLR; ABCA1; Lipid homeostasis; Atherosclerosis
ID CHOLESTEROL HOMEOSTASIS; FAMILIAL HYPERCHOLESTEROLEMIA; CELLULAR
CHOLESTEROL; MOUSE MODELS; METABOLISM; MICRORNAS; RECEPTOR;
ATHEROSCLEROSIS; PATHWAY; BINDING
AB Rationale: Recently, there has been significant interest in the therapeutic administration of miRNA mimics and inhibitors to treat cardiovascular disease. In particular, miR-27b has emerged as a regulatory hub in cholesterol and lipid metabolism and potential therapeutic target for treating atherosclerosis. Despite this, the impact of miR-27b on lipid levels in vivo remains to be determined. As such, here we set out to further characterize the role of miR-27b in regulating cholesterol metabolism in vitro and to determine the effect of miR-27b overexpression and inhibition on circulating and hepatic lipids in mice.
Methods and results: Our results identify miR-27b as an important regulator of LDLR activity in human and mouse hepatic cells through direct targeting of LDLR and LDLRAP1. In addition, we report that modulation of miR-27b expression affects ABCA1 protein levels and cellular cholesterol efflux to ApoA1 in human hepatic Huh7 cells. Overexpression of pre-miR-27b in the livers of wild-type mice using AAV8 vectors increased pre-miR-27b levels 50efold and reduced hepatic ABCA1 and LDLR expression by 50% and 20%, respectively, without changing circulating and hepatic cholesterol and triglycerides. To determine the effect of endogenous miR-27b on circulating lipids, wild-type mice were fed a Western diet for one month and injected with 5 mg/kg of LNA control or LNA anti-miR-27b oligonucleotides. Following two weeks of treatment, the expression of ABCA1 and LDLR were increased by 10-20% in the liver, demonstrating effective inhibition of miR-27b function. Intriguingly, no differences in circulating and hepatic lipids were observed between treatment groups.
Conclusions: The results presented here provide evidence that short-term modulation of miR-27b expression in wild-type mice regulates hepatic LDLR and ABCA1 expression but does not influence plasma and hepatic lipid levels. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
C1 [Goedeke, Leigh; Rotllan, Noemi; Ramirez, Cristina M.; Aranda, Juan F.; Canfran-Duque, Alberto; Araldi, Elisa; Fernandez-Hernando, Ana; Suarez, Yajaira; Fernandez-Hernando, Carlos] Yale Univ, Sch Med, Comparat Med Sect, Dept Pathol,Program Integrat Cell Signaling & Neu, New Haven, CT 06520 USA.
[Goedeke, Leigh; Rotllan, Noemi; Ramirez, Cristina M.; Aranda, Juan F.; Canfran-Duque, Alberto; Araldi, Elisa; Fernandez-Hernando, Ana; Suarez, Yajaira; Fernandez-Hernando, Carlos] Yale Univ, Sch Med, Vasc Biol & Therapeut Program, New Haven, CT 06520 USA.
[de Cabo, Rafael] NIA, Translat Gerontol Branch, NIH, Baltimore, MD 21224 USA.
[Langhi, Cedric; Baldan, Angel] St Louis Univ, Sch Med, Ctr Cardiovasc Res, Edward A Doisy Dept Biochem & Mol Biol, St Louis, MO USA.
RP Fernandez-Hernando, C (reprint author), 10 Amistad St,Room 320, New Haven, CT 06520 USA.
EM carlos.fernandez@yale.edu
RI de Cabo, Rafael/J-5230-2016;
OI de Cabo, Rafael/0000-0002-3354-2442; Ramirez, Cristina
M/0000-0003-2589-0786; , rafael/0000-0003-2830-5693
FU National Institutes of Health [R01HL107953, R01HL107953-04S1,
R01HL106063, R01HL105945, 1F31AG043318, R01HL107794]; American Heart
Association [15SDG23000025, GRNT20460189]; Howard Hughes Medical
Institute International Student Research Fellowship; Foundation Leducq
Transatlantic Network of Excellence in Cardiovascular Research
FX This work was supported by grants from the National Institutes of Health
(R01HL107953, R01HL107953-04S1, and R01HL106063 to CF-H; R01HL105945 to
YS; 1F31AG043318 to LG; and R01HL107794 to AB), the American Heart
Association (15SDG23000025 to CMR and GRNT20460189 to AB), the Howard
Hughes Medical Institute International Student Research Fellowship (to
EA), and the Foundation Leducq Transatlantic Network of Excellence in
Cardiovascular Research (to CFH).
NR 41
TC 9
Z9 9
U1 1
U2 3
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0021-9150
EI 1879-1484
J9 ATHEROSCLEROSIS
JI Atherosclerosis
PD DEC
PY 2015
VL 243
IS 2
BP 499
EP 509
DI 10.1016/j.atherosclerosis.2015.09.033
PG 11
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA CY6QO
UT WOS:000366534100022
PM 26520906
ER
PT J
AU Kreitman, RJ
Pastan, I
AF Kreitman, Robert J.
Pastan, Ira
TI Immunoconjugates in the management of hairy cell leukemia
SO BEST PRACTICE & RESEARCH CLINICAL HAEMATOLOGY
LA English
DT Article
DE Moxetumomab pasudotox; BL22; CD22; CD25; Recombinant immunotoxin;
Pseudomonas exotoxin
ID TERM-FOLLOW-UP; IMMUNOTOXIN RFB4(DSFV)-PE38 BL22; CHRONIC
LYMPHOCYTIC-LEUKEMIA; SINGLE-CHAIN IMMUNOTOXIN; PHASE-I TRIAL;
PSEUDOMONAS-EXOTOXIN; RECOMBINANT IMMUNOTOXIN; DIPHTHERIA-TOXIN;
CYTOTOXIC ACTIVITY; ANTI-TAC
AB Hairy cell leukemia (HCL) is an indolent B-cell malignancy effectively treated but not often cured by purine analog therapy; after multiple courses of purine analogs, patients can become purine analog resistant and in need of alternative therapies. Complete remission to single-agent purine analog is often accompanied by minimal residual disease (MRD), residual HCL cells detectable by immunologic methods, considered a risk factor for eventual relapse. Several different non-chemotherapy approaches are being used to target relapsed and refractory HCL, including inhibitors of BRAF, but so far only monoclonal antibody (MAb)-based approaches have been reported to eliminate MRD in a high percentage of patients. One of the MAb-based options for HCL currently under clinical investigation involves recombinant immunotoxins, containing a fragment of a MAb and a bacterial toxin. The bacterial toxin, a highly potent fragment from Pseudomonas exotoxin, catalytically ADP-ribosylates elongation factor 2 (EF2), resulting in protein synthesis inhibition and apoptotic cell death. Recombinant immunotoxins tested in HCL patients include LMB-2, targeting CD25, and BL22, targeting CD22. An affinity matured version of BL22, termed moxetumomab pasudotox (formerly HA22 or CAT-8015) achieved high CR rates in phase I, and is currently undergoing multicenter Phase 3 testing. Phase I testing was without dose-limiting toxicity, although 2 patients had grade 2 hemolytic uremic syndrome (HUS) with transient grade 1 abnormalities in platelets and creatinine. Preclinical work is underway to identify residues on moxetumomab pasudotox leading to immunogenicity. Moxetumomab pasudotox is undergoing pivotal testing for relapsed and refractory HCL. Published by Elsevier Ltd.
C1 [Kreitman, Robert J.; Pastan, Ira] NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Kreitman, RJ (reprint author), NCI, Mol Biol Lab, NIH, 37-5124B,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM kreitmar@mail.nih.gov
FU NIH; Hairy Cell Leukemia Foundation
FX Research in this review was supported in part by the intramural program
of the NIH and the Hairy Cell Leukemia Foundation.
NR 79
TC 6
Z9 6
U1 0
U2 0
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1521-6926
EI 1532-1924
J9 BEST PRACT RES CL HA
JI Best Pract. Res. Clin. Haematol.
PD DEC
PY 2015
VL 28
IS 4
BP 236
EP 245
DI 10.1016/j.beha.2015.09.003
PG 10
WC Hematology
SC Hematology
GA CZ0BU
UT WOS:000366770900010
PM 26614902
ER
PT J
AU Natrajan, MS
de la Fuente, AG
Crawford, AH
Linehan, E
Nunez, V
Johnson, KR
Wu, TX
Fitzgerald, DC
Ricote, M
Bielekova, B
Franklin, RJM
AF Natrajan, Muktha S.
de la Fuente, Alerie G.
Crawford, Abbe H.
Linehan, Eimear
Nunez, Vanessa
Johnson, Kory R.
Wu, Tianxia
Fitzgerald, Denise C.
Ricote, Mercedes
Bielekova, Bibiana
Franklin, Robin J. M.
TI Retinoid X receptor activation reverses age-related deficiencies in
myelin debris phagocytosis and remyelination
SO BRAIN
LA English
DT Article
DE remyelination; ageing; retinoid X receptor; myelin debris;
monocyte-derived macrophages
ID CENTRAL-NERVOUS-SYSTEM; OLIGODENDROCYTE PRECURSOR CELLS;
MULTIPLE-SCLEROSIS LESIONS; CNS REMYELINATION; ADULT CNS; ALTERNATIVE
ACTIVATION; LUPUS-ERYTHEMATOSUS; T-CELLS; MACROPHAGES; MICROGLIA
AB The efficiency of central nervous system remyelination declines with age. This is in part due to an age-associated decline in the phagocytic removal of myelin debris, which contains inhibitors of oligodendrocyte progenitor cell differentiation. In this study, we show that expression of genes involved in the retinoid X receptor pathway are decreased with ageing in both myelin-phagocytosing human monocytes and mouse macrophages using a combination of in vivo and in vitro approaches. Disruption of retinoid X receptor function in young macrophages, using the antagonist HX531, mimics ageing by reducing myelin debris uptake. Macrophage-specific RXR alpha (Rxra) knockout mice revealed that loss of function in young mice caused delayed myelin debris uptake and slowed remyelination after experimentally-induced demyelination. Alternatively, retinoid X receptor agonists partially restored myelin debris phagocytosis in aged macrophages. The agonist bexarotene, when used in concentrations achievable in human subjects, caused a reversion of the gene expression profile in multiple sclerosis patient monocytes to a more youthful profile and enhanced myelin debris phagocytosis by patient cells. These results reveal the retinoid X receptor pathway as a positive regulator of myelin debris clearance and a key player in the age-related decline in remyelination that may be targeted by available or newly-developed therapeutics.
C1 [Natrajan, Muktha S.; de la Fuente, Alerie G.; Crawford, Abbe H.; Franklin, Robin J. M.] Univ Cambridge, Wellcome Trust MRC Cambridge Stem Cell Inst, Cambridge CB2 0AH, England.
[Natrajan, Muktha S.; de la Fuente, Alerie G.; Crawford, Abbe H.; Franklin, Robin J. M.] Univ Cambridge, Dept Clin Neurosci, Cambridge CB2 0AH, England.
[Natrajan, Muktha S.; Johnson, Kory R.; Wu, Tianxia; Bielekova, Bibiana] NINDS, Neuroimmunol Dis Unit, NIH, Bethesda, MD 20892 USA.
[Linehan, Eimear; Fitzgerald, Denise C.] Queens Univ Belfast, Ctr Infect & Immun, Belfast BT7 1NN, Antrim, North Ireland.
[Nunez, Vanessa; Ricote, Mercedes] Ctr Nacl Invest Cardiovasc Carlos III CNIC, Dept Cardiovasc Dev & Repair, Madrid, Spain.
RP Franklin, RJM (reprint author), Univ Cambridge, Wellcome Trust MRC Cambridge Stem Cell Inst, Clifford Allbutt Bldg,Cambridge Biomed Campus, Cambridge CB2 0AH, England.
EM Bibi.Bielekova@nih.gov; rjf1000@cam.ac.uk
RI Ricote, Mercedes/L-4615-2014
OI Ricote, Mercedes/0000-0002-8090-8902
FU UK Multiple Sclerosis Society; Wellcome-Trust; NINDS/NIH Intramural
Research Program; Health Research Board Scholars Program;
Gates-Cambridge Scholarship; Spanish Ministry of Economy and
Competitiveness [SAF2012-31483]
FX This work was supported by grants from the UK Multiple Sclerosis
Society, Wellcome-Trust, NINDS/NIH Intramural Research Program, Health
Research Board Scholars Program, Gates-Cambridge Scholarship, and
Spanish Ministry of Economy and Competitiveness (SAF2012-31483).
NR 70
TC 8
Z9 8
U1 1
U2 10
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 DEC 1
PY 2015
VL 138
BP 3581
EP 3597
DI 10.1093/brain/awv289
PN 12
PG 17
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA CY4NK
UT WOS:000366384600020
PM 26463675
ER
PT J
AU Wang, TW
Vermeulen, RCH
Hu, W
Liu, G
Xiao, XH
Alekseyev, Y
Xu, J
Reiss, B
Steiling, K
Downward, GS
Silverman, DT
Wei, FS
Wu, GP
Li, JH
Lenburg, ME
Rothman, N
Spira, A
Lan, Q
AF Wang, Teresa W.
Vermeulen, Roel C. H.
Hu, Wei
Liu, Gang
Xiao, Xiaohui
Alekseyev, Yuriy
Xu, Jun
Reiss, Boris
Steiling, Katrina
Downward, George S.
Silverman, Debra T.
Wei, Fusheng
Wu, Guoping
Li, Jihua
Lenburg, Marc E.
Rothman, Nathaniel
Spira, Avrum
Lan, Qing
TI Gene-expression profiling of buccal epithelium among non-smoking women
exposed to household air pollution from smoky coal
SO CARCINOGENESIS
LA English
DT Article
ID LUNG-CANCER RISK; ENDOTHELIAL GROWTH-FACTOR; XUAN-WEI; CIGARETTE-SMOKE;
DIAGNOSTIC EVALUATION; COMBUSTION EMISSIONS; ENRICHMENT ANALYSIS;
BRONCHIAL AIRWAY; FUYUAN COUNTIES; HEALTH IMPACTS
AB In China's rural counties of Xuanwei and Fuyuan, lung cancer rates are among the highest in the world. While the elevated disease risk in this population has been linked to the usage of smoky (bituminous) coal as compared to smokeless (anthracite) coal, the underlying molecular changes associated with this exposure remains unclear. To understand the physiologic effects of smoky coal exposure, we analyzed the genome-wide gene-expression profiles in buccal epithelial cells collected from healthy, non-smoking female residents of Xuanwei and Fuyuan who burn smoky (n = 26) and smokeless (n = 9) coal. Gene-expression was profiled via microarrays, and changes associated with coal type were correlated to household levels of fine particulate matter (PM 2.5) and polycyclic aromatic hydrocarbons (PAHs). Expression levels of 282 genes were altered with smoky versus smokeless coal exposure (P < 0.005), including the 2-fold increase of proinflammatory IL8 and decrease of proapoptotic CASP3. This signature was more correlated with carcinogenic PAHs (e.g. Benzo[a] pyrene; r = 0.41) than with non-carcinogenic PAHs (e.g. Fluorene; r = 0.08) or PM 2.5 (r = 0.05). Genes altered with smoky coal exposure were concordantly enriched with tobacco exposure in previously profiled buccal biopsies of smokers and non-smokers (GSEA, q < 0.05). This is the first study to identify a signature of buccal epithelial gene-expression that is associated with smoky coal exposure, which in part is similar to the molecular response to tobacco smoke, thereby lending biologic plausibility to prior epidemiological studies that have linked this exposure to lung cancer risk.
C1 [Wang, Teresa W.; Liu, Gang; Xiao, Xiaohui; Steiling, Katrina; Lenburg, Marc E.; Spira, Avrum] Boston Univ, Sch Med, Div Computat Biomed, Boston, MA 02118 USA.
[Wang, Teresa W.; Steiling, Katrina; Lenburg, Marc E.; Spira, Avrum] Boston Univ, Bioinformat Program, Boston, MA 02215 USA.
[Vermeulen, Roel C. H.; Reiss, Boris; Downward, George S.] Univ Utrecht, Div Environm Epidemiol, Inst Risk Assessment Sci, Utrecht, Netherlands.
[Hu, Wei; Silverman, Debra T.; Rothman, Nathaniel; Lan, Qing] NCI, Div Canc Epidemiol & Genet, Rockville, MD 20850 USA.
[Alekseyev, Yuriy; Lenburg, Marc E.; Spira, Avrum] Boston Univ, Sch Med, Dept Pathol & Lab Med, Boston, MA 02118 USA.
[Xu, Jun] Univ Hong Kong, Sch Publ Hlth, Hong Kong, Hong Kong, Peoples R China.
[Reiss, Boris] Univ Washington, Sch Publ Hlth, Seattle, WA 98195 USA.
[Wei, Fusheng; Wu, Guoping] China Natl Environm Monitoring Ctr, Beijing, Peoples R China.
[Li, Jihua] Qujing Ctr Dis Control & Prevent, Qujing, Peoples R China.
RP Spira, A (reprint author), Boston Univ, Sch Med, Div Computat Biomed, Boston, MA 02118 USA.
EM aspira@bu.edu; qingl@mail.nih.gov
RI Lenburg, Marc/B-8027-2008; Vermeulen, Roel/F-8037-2011
OI Lenburg, Marc/0000-0002-5760-4708; Vermeulen, Roel/0000-0003-4082-8163
FU National Institutes of Health/National Institute of Environmental Health
Sciences [3U01ES16035-03S1]; Intramural Research Program of the US
National Cancer Institute
FX National Institutes of Health/National Institute of Environmental Health
Sciences (3U01ES16035-03S1); Intramural Research Program of the US
National Cancer Institute.
NR 50
TC 1
Z9 1
U1 6
U2 16
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 DEC
PY 2015
VL 36
IS 12
BP 1494
EP 1501
DI 10.1093/carcin/bgv150
PG 8
WC Oncology
SC Oncology
GA CY4ON
UT WOS:000366387600005
PM 26468118
ER
PT J
AU La Maestra, S
D'Agostini, F
Izzotti, A
Micale, RT
Mastracci, L
Camoirano, A
Balansky, R
Trosko, JE
Steele, VE
De Flora, S
AF La Maestra, Sebastiano
D'Agostini, Francesco
Izzotti, Alberto
Micale, Rosanna T.
Mastracci, Luca
Camoirano, Anna
Balansky, Roumen
Trosko, James E.
Steele, Vernon E.
De Flora, Silvio
TI Modulation by aspirin and naproxen of nucleotide alterations and tumors
in the lung of mice exposed to environmental cigarette smoke since birth
SO CARCINOGENESIS
LA English
DT Article
ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; STEM-CELL THEORY; TOBACCO-SMOKE;
CANCER-RISK; N-ACETYLCYSTEINE; URINARY-BLADDER; GENE-EXPRESSION; RODENT
MODELS; CARCINOGENESIS; INFLAMMATION
AB Chemoprevention provides an important strategy for cancer control in passive smokers. Due to the crucial role played by smoke-related chronic inflammation in lung carcinogenesis, of special interest are extensively used pharmacological agents, such as nonsteroidal anti-inflammatory drugs (NSAIDs). We evaluated the ability of aspirin and naproxen, inhibitors of both cyclooxygenase-1 and cyclooxygenase -2, to modulate environmental cigarette smoke (ECS)-induced lung carcinogenesis in A/J mice of both genders. Based on a subchronic toxicity study in 180 postweaning mice, we used 1600 mg/kg diet aspirin and 320 mg/kg diet naproxen. In the tumor chemoprevention study, using 320 mice, exposure to ECS started soon after birth and administration of NSAIDs started after weaning. At 10 weeks of life, the NSAIDs did not affect the presence of occult blood in feces. As assessed in a subset of 40 mice, bulky DNA adducts and 8-hydroxy-2'-deoxyguanosine levels were considerably increased in ECS-exposed mice and, irrespective of gender, both NSAIDs remarkably inhibited these nucleotide alterations. After exposure for 4 months followed by 5 months in filtered air, ECS induced a significant increase in the yield of surface lung tumors, the 43.7% of which were adenomas and the 56.3% were adenocarcinomas. Oct-4 (octamer-binding transcription factor 4), a marker of cell stemness, was detected in some adenocarcinoma cells. The NAIDs attenuated the yield of lung tumors, but prevention of ECS-induced lung adenomas was statistically significant only in female mice treated with aspirin, which supports a role for estrogens in ECS-related lung carcinogenesis and highlights the antiestrogenic properties of NSAIDs.
C1 [La Maestra, Sebastiano; D'Agostini, Francesco; Izzotti, Alberto; Micale, Rosanna T.; Camoirano, Anna; De Flora, Silvio] Univ Genoa, Dept Hlth Sci, I-16132 Genoa, Italy.
[Mastracci, Luca] Univ Genoa, Dept Surg & Diagnost Sci, I-16132 Genoa, Italy.
[Balansky, Roumen] Natl Oncol Ctr, Sofia 1756, Bulgaria.
[Trosko, James E.] Michigan State Univ, Dept Pediat & Human Dev, Natl Food Safety Toxicol Ctr, E Lansing, MI 48824 USA.
[Steele, Vernon E.] NCI, Canc Prevent Div, Chemoprevent Agent Dev Res Grp, Bethesda, MD 20892 USA.
RP De Flora, S (reprint author), Univ Genoa, Dept Hlth Sci, I-16132 Genoa, Italy.
EM sdf@unige.it
OI izzotti, alberto/0000-0002-8588-0347
FU United States National Cancer Institute [HHSN-261201200015I]
FX United States National Cancer Institute (Contract #HHSN-261201200015I).
NR 51
TC 3
Z9 3
U1 0
U2 0
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 DEC
PY 2015
VL 36
IS 12
BP 1531
EP 1538
DI 10.1093/carcin/bgv149
PG 8
WC Oncology
SC Oncology
GA CY4ON
UT WOS:000366387600009
PM 26464196
ER
PT J
AU Nicolaou, KC
Rhoades, D
Wang, YP
Totokotsopoulos, S
Bai, RL
Hamel, E
AF Nicolaou, K. C.
Rhoades, Derek
Wang, Yanping
Totokotsopoulos, Sotirios
Bai, Ruoli
Hamel, Ernest
TI Synthesis and Biological Evaluation of Novel EpothiloneB Side Chain
Analogues
SO CHEMMEDCHEM
LA English
DT Article
DE antibody-drug conjugates; anticancer agents; epothilones; organic
synthesis; tubulin binding agents
ID HIGHLY POTENT EPOTHILONE; STEREOSELECTIVE-SYNTHESIS; CHEMICAL-SYNTHESIS;
STANNOUS CHLORIDE; (-)-EPOTHILONE B; TUBULIN; CONFORMATION; REDUCTION;
CATALYSIS; STRATEGY
AB The design, synthesis, and biological evaluation of a series of epothilone analogues with novel side chains equipped with an amino group are described. Their design facilitates potential conjugation to selective drug delivery systems such as antibodies. Their synthesis proceeded efficiently via Stille coupling of a readily available vinyl iodide and heterocyclic stannanes. Cytotoxicity studies and tubulin binding assays revealed two of these analogues to be more potent than epothilonesA-D and the anticancer agent ixabepilone, currently in clinical use.
C1 [Nicolaou, K. C.; Rhoades, Derek; Wang, Yanping; Totokotsopoulos, Sotirios] Rice Univ, Dept Chem, Houston, TX 77005 USA.
[Rhoades, Derek] Univ Calif San Diego, Dept Chem & Biochem, La Jolla, CA 92093 USA.
[Totokotsopoulos, Sotirios] Scripps Res Inst, Dept Chem, La Jolla, CA 92037 USA.
[Bai, Ruoli; Hamel, Ernest] NCI, Screening Technol Branch, Dev Therapeut Program,NIH, Div Canc Treatment & Diag,Frederick Natl Lab Canc, Frederick, MD 21702 USA.
RP Nicolaou, KC (reprint author), Rice Univ, Dept Chem, 6100 Main St, Houston, TX 77005 USA.
EM kcn@rice.edu
FU Cancer Prevention & Research Institute of Texas (CPRIT); Welch
Foundation [C-1819]; Bristol-Myers Squibb
FX This work was partially carried out at The Scripps Research Institute
(TSRI). We thank Drs. D. H. Huang (TSRI), L. Pasternack (TSRI), L. B.
Alemany (Rice Univ.), and Q. Kleerekoper (Rice Univ.) for NMR
spectroscopic assistance, and Drs. G. Siuzdak (TSRI) and C. Pennington
(Rice Univ.) for assistance with mass spectrometry. This work was
supported by the Cancer Prevention & Research Institute of Texas
(CPRIT), the Welch Foundation (grant C-1819), and Bristol-Myers Squibb.
Disclaimer by the co-authors based at NCI (R.L. and E.H.): The content
of this article is the sole responsibility of the authors and does not
necessarily reflect the official views of the US National Institutes of
Health.
NR 52
TC 0
Z9 0
U1 6
U2 23
PU WILEY-V C H VERLAG GMBH
PI WEINHEIM
PA POSTFACH 101161, 69451 WEINHEIM, GERMANY
SN 1860-7179
EI 1860-7187
J9 CHEMMEDCHEM
JI ChemMedChem
PD DEC
PY 2015
VL 10
IS 12
BP 1974
EP 1979
DI 10.1002/cmdc.201500401
PG 6
WC Chemistry, Medicinal; Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA CY6HY
UT WOS:000366511000004
PM 26447977
ER
PT J
AU Tang, KS
Klempner, MS
Wormser, GP
Marques, AR
Alaedini, A
AF Tang, Kevin S.
Klempner, Mark S.
Wormser, Gary P.
Marques, Adriana R.
Alaedini, Armin
TI Association of Immune Response to Endothelial Cell Growth Factor With
Early Disseminated and Late Manifestations of Lyme Disease but Not
Posttreatment Lyme Disease Syndrome
SO CLINICAL INFECTIOUS DISEASES
LA English
DT Editorial Material
DE Lyme disease; posttreatment Lyme disease syndrome; endothelial cell
growth factor; antibody; Borrelia burgdorferi
ID SYMPTOMS
AB Endothelial cell growth factor has been recently proposed as a potential autoantigen in manifestations of Lyme disease that are thought to involve immune-mediated mechanisms. Our findings indicate that a humoral immune response to this protein is not associated with posttreatment Lyme disease syndrome.
C1 [Tang, Kevin S.; Alaedini, Armin] Columbia Univ, Med Ctr, Dept Med, New York, NY 10032 USA.
[Klempner, Mark S.] Univ Massachusetts, Sch Med, MassBiol, Boston, MA 02125 USA.
[Wormser, Gary P.] New York Med Coll, Dept Med, Div Infect Dis, Valhalla, NY 10595 USA.
[Marques, Adriana R.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
RP Alaedini, A (reprint author), Columbia Univ, Med Ctr, Dept Med, 1130 St Nicholas Ave,Rm 937, New York, NY 10032 USA.
EM aa819@columbia.edu
FU Intramural NIH HHS; NIAID NIH HHS [N01AI65308, R56AI093763, R56
AI093763]
NR 12
TC 2
Z9 2
U1 1
U2 2
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 DEC 1
PY 2015
VL 61
IS 11
BP 1703
EP 1706
DI 10.1093/cid/civ638
PG 4
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA CY5RF
UT WOS:000366464200011
PM 26219695
ER
PT J
AU Koo, PJ
Kwak, JJ
Pokharel, S
Choyke, PL
AF Koo, Phillip J.
Kwak, Jennifer J.
Pokharel, Sajal
Choyke, Peter L.
TI Novel Imaging of Prostate Cancer with MRI, MRI/US, and PET
SO CURRENT ONCOLOGY REPORTS
LA English
DT Review
DE Prostate cancer; MRI; MRI/US; Fusion; DWI; DKI; Hyperpolarized; PET;
PET/CT; PSMA; FACBC; Acetate; Bombesin; GRP; FDHT
ID GASTRIN-RELEASING-PEPTIDE; POSITRON-EMISSION-TOMOGRAPHY; ACID SYNTHASE
EXPRESSION; MEMBRANE ANTIGEN; ANDROGEN-RECEPTOR; RADICAL PROSTATECTOMY;
ANTI-1-AMINO-3-F-18-FLUOROCYCLOBUTANE-1-CARBOXYLIC ACID; TARGETED
BIOPSY; FUSION; CASTRATION
AB Imaging of prostate cancer presents many challenges to the imaging community. There has been much progress in this space in large part due to MRI and PET radiopharmaceuticals. Though MRI has been focused on the evaluation of local disease and PETon the detection of metastatic disease, these two areas do converge and will be complementary especially with the growth of new PET/MRI technologies. In this review article, we review novel MRI, MRI/US, and PET radiopharmaceuticals which will offer insight into the future direction of imaging in prostate cancer.
C1 [Koo, Phillip J.; Kwak, Jennifer J.] Univ Colorado, Sch Med, Dept Radiol, Div Nucl Med & Mol Imaging, Aurora, CO 80045 USA.
[Pokharel, Sajal] Univ Colorado, Sch Med, Dept Radiol, Div Abdominal Imaging, Aurora, CO 80045 USA.
[Choyke, Peter L.] NCI, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Koo, PJ (reprint author), Univ Colorado, Sch Med, Dept Radiol, Div Nucl Med & Mol Imaging, Mail Stop L954,12401 E 17th Ave,Room 1512, Aurora, CO 80045 USA.
EM phillip.koo@ucdenver.edu; jennifer.kwak@ucdenver.edu;
sajal.pokharel@ucdenver.edu; pchoyke@nih.gov
NR 85
TC 3
Z9 3
U1 2
U2 13
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1523-3790
EI 1534-6269
J9 CURR ONCOL REP
JI Curr. Oncol. Rep.
PD DEC
PY 2015
VL 17
IS 12
AR 56
DI 10.1007/s11912-015-0480-y
PG 10
WC Oncology
SC Oncology
GA CZ0PG
UT WOS:000366807600004
PM 26462919
ER
PT J
AU Lucas, CL
Lenardo, MJ
AF Lucas, Carrie L.
Lenardo, Michael J.
TI Identifying genetic-determinants of autoimmunity and immune
dysregulation
SO CURRENT OPINION IN IMMUNOLOGY
LA English
DT Review
ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; GENOME-WIDE ASSOCIATION; X-LINKED
SYNDROME; LYMPHOPROLIFERATIVE-SYNDROME; RHEUMATOID-ARTHRITIS; HUMAN
IMMUNODEFICIENCY; DEFECTIVE LYMPHOCYTE; AIRE GENE; MUTATIONS; DISEASE
AB Common autoimmune diseases are relatively heterogeneous with both genetic and environmental factors influencing disease susceptibility and progression. As the populations in developed countries age, these chronic diseases will become an increasing burden in human suffering and health care costs. By contrast, rare immune diseases that are severe and develop early in childhood are frequently monogenic and fully penetrant, often with a Mendelian inheritance pattern. Although these may be incompatible with survival or cured by hematopoietic stem cell transplantation, we will argue that they constitute a rich source of genetic insights into immunological diseases. Here, we discuss five examples of well-studied Mendelian disease-causing genes and their known or predicted roles in conferring susceptibility to common, polygenic diseases of autoimmunity. Mendelian disease mutations, as experiments of nature, reveal human loci that are indispensable for immune regulation and, therefore, most promising as therapeutic targets.
C1 [Lucas, Carrie L.; 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, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM lenardo@nih.gov
FU Intramural Research Program of NIH, NIAID; Postdoctoral Research
Associate (PRAT) Fellowship, NIGMS, NIH
FX This work was supported by the Intramural Research Program of NIH,
NIAID. C.L.L. was supported by the Postdoctoral Research Associate
(PRAT) Fellowship, NIGMS, NIH. The authors thank Drs. Helen Su and Yu
Zhang for critically reading the manuscript.
NR 52
TC 2
Z9 2
U1 2
U2 6
PU CURRENT BIOLOGY LTD
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0952-7915
EI 1879-0372
J9 CURR OPIN IMMUNOL
JI Curr. Opin. Immunol.
PD DEC
PY 2015
VL 37
BP 28
EP 33
DI 10.1016/j.coi.2015.09.001
PG 6
WC Immunology
SC Immunology
GA CZ0FK
UT WOS:000366780300006
PM 26433354
ER
PT J
AU Boyd, A
Killoran, K
Mitre, E
Nutman, TB
AF Boyd, Alexis
Killoran, Kristin
Mitre, Edward
Nutman, Thomas B.
TI Pleural cavity type 2 innate lymphoid cells precede Th2 expansion in
murine Litomosoides sigmodontis infection
SO EXPERIMENTAL PARASITOLOGY
LA English
DT Article
DE Lymphocytes; Filaria; Pleural cavity; Innate lymphoid cells; ILC2s
ID IMMUNITY; MICE; FILARIASIS; BASOPHILS; RESPONSES
AB Recently, a family of innate cells has been identified that respond to IL-25 and IL-33 in murine intestinal helminths. Termed Type 2 innate lymphoid cells (ILC2s) they facilitate the development of Th2 responses responsible for helminth clearance. We evaluated these cells in a tissue-invasive helminth model. Using Litomosides sigmodontis (a strong Th2 polarizing filarial infection) we observed a robust Th2 response in the pleural cavity, where adult worms reside, marked by increased levels of IL-5 and IL-13 in infected mice. In parallel, ILC2s were expanded in the pleural cavity early in the infection, peaking during the prepatent period. L sigmodontis also elicits a strong systemic Th2 response, which includes significantly increased levels of IgG1, IgE and IL-5 in the plasma of infected mice. Although ILC2s were expanded locally, they were not expanded in the spleen, blood, or mediastinal lymph nodes in response to L sigmodontis infection, suggesting that ILC2s function primarily at the site of infection. The increase in ILC2s in the pleural cavity and the expansion in Th2 responses indicates a probable role for these cells in initiating and maintaining the Th2 response and highlights the importance of these cells in helminth infections and their role in Th2 immunity. Published by Elsevier Ltd.
C1 [Boyd, Alexis; Nutman, Thomas B.] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
[Killoran, Kristin; Mitre, Edward] Uniformed Serv Univ Hlth Sci, Dept Microbiol & Immunol, F Edward Hebert Sch Med, Bethesda, MD 20892 USA.
RP Nutman, TB (reprint author), NIAID, Parasit Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM tnutman@niaid.nih.gov
FU Division of Intramural Research (DIR), NIAID
FX Alexis Boyd was a predoctoral student in the Microbiology and Immunology
program of the Institute for Biomedical Sciences at the George
Washington University. This work is from a dissertation that was
presented in partial fulfillment of the requirements for the Ph.D.
degree. The work was supported, in part, by the Division of Intramural
Research (DIR), NIAID.
NR 19
TC 0
Z9 0
U1 1
U2 2
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0014-4894
EI 1090-2449
J9 EXP PARASITOL
JI Exp. Parasitol.
PD DEC
PY 2015
VL 159
BP 118
EP 126
DI 10.1016/j.exppara.2015.09.006
PG 11
WC Parasitology
SC Parasitology
GA CY5JC
UT WOS:000366442900016
PM 26394284
ER
PT J
AU Ehrenshaft, M
Deterding, LJ
Mason, RP
AF Ehrenshaft, Marilyn
Deterding, Leesa J.
Mason, Ronald P.
TI Tripping up Trp: Modification of protein tryptophan residues by reactive
oxygen species, modes of detection, and biological consequences
SO FREE RADICAL BIOLOGY AND MEDICINE
LA English
DT Review
DE Tryptophan; Protein; Oxidation; Radical; Singlet oxygen; Ozone;
Kynurenine; N-formylkynurenine; Fluorescence; Mass spectrometry;
Anti-NFK; ESR; ESR spin trapping; Lysozyme; hSOD1; alpha-crystallin;
Apolipoprotein; Photosynthesis; MopE
ID LOW-DENSITY-LIPOPROTEIN; TORPEDO-CALIFORNICA ACETYLCHOLINESTERASE;
AMYOTROPHIC-LATERAL-SCLEROSIS; TANDEM MASS-SPECTROMETRY; PHOTOSENSITIZER
METHYLENE-BLUE; ZN-SUPEROXIDE-DISMUTASE; LENS ALPHA-CRYSTALLIN;
EGG-WHITE LYSOZYME; N-FORMYLKYNURENINE; SINGLET OXYGEN
AB Proteins comprise a majority of the dry weight of a cell, rendering them a major target for oxidative modification. Oxidation of proteins can result in significant alterations in protein molecular mass such as breakage of the polypeptide backbone and/or polymerization of monomers into dimers, multimers, and sometimes insoluble aggregates. Protein oxidation can also result in structural changes to amino acid residue side chains, conversions that have only a modest effect on protein size but can have widespread consequences for protein function. There are a wide range of rate constants for amino acid reactivity, with cysteine, methionine, tyrosine, phenylalanine, and tryptophan having the highest rate constants with commonly encountered biological oxidants. Free tryptophan and tryptophan protein residues react at a diffusion-limited rate with hydroxyl radical and also have high rate constants for reactions with singlet oxygen and ozone. Although oxidation of proteins in general and tryptophan residues specifically can have effects detrimental to the health of cells and organisms, some modifications are neutral, whereas others contribute to the function of the protein in question or may act as a signal that damaged proteins need to be replaced. This review provides a brief overview of the chemical mechanisms by which tryptophan residues become oxidized, presents both the strengths and the weaknesses of some of the techniques used to detect these oxidative interactions, and discusses selected examples of the biological consequences of tryptophan oxidation in proteins from animals, plants, and microbes. Published by Elsevier Inc.
C1 [Ehrenshaft, Marilyn; Mason, Ronald P.] Immun Inflammat & Dis Lab, Res Triangle Pk, NC 27709 USA.
[Ehrenshaft, Marilyn; Mason, Ronald P.] NIEHS, NIH, Res Triangle Pk, NC 27709 USA.
[Deterding, Leesa J.] NIEHS, Epigenet & Stem Cell Biol Lab, NIH, Res Triangle Pk, NC 27709 USA.
RP Ehrenshaft, M (reprint author), Immun Inflammat & Dis Lab, Res Triangle Pk, NC 27709 USA.
EM ehrensh1@niehs.nih.gov
FU Intramural Research Program of the NIEHS, NIH
FX We thank B. Jean Corbett, Dr. Ann Motten, and Mary J. Mason for valuable
help in the preparation of the manuscript. This work was supported by
the Intramural Research Program of the NIEHS, NIH.
NR 95
TC 4
Z9 4
U1 10
U2 40
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 DEC
PY 2015
VL 89
BP 220
EP 228
DI 10.1016/j.freeradbiomed.2015.08.003
PG 9
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA CY4CI
UT WOS:000366355800021
PM 26393422
ER
PT J
AU Delmastro-Greenwood, M
Hughan, KS
Vitturi, DA
Salvatore, SR
Grimes, G
Potti, G
Shiva, S
Schopfer, FJ
Gladwin, MT
Freeman, BA
Wendell, SG
AF Delmastro-Greenwood, Meghan
Hughan, Kara S.
Vitturi, Dario A.
Salvatore, Sonia R.
Grimes, George
Potti, Gopal
Shiva, Sruti
Schopfer, Francisco J.
Gladwin, Mark T.
Freeman, Bruce A.
Wendell, Stacy Gelhaus
TI Nitrite and nitrate-dependent generation of anti-inflammatory fatty acid
nitroalkenes
SO FREE RADICAL BIOLOGY AND MEDICINE
LA English
DT Article
DE Nitrogen metabolism; Diet; Redox signaling; Nitro-fatty acid; Conjugated
linoleic acid; Nitrate; Nitrite
ID CONJUGATED LINOLEIC-ACID; HEALTHY HUMANS; OLEIC ACID; INFLAMMATION;
CIS-9,TRANS-11; THERAPEUTICS; HYPERTENSION; MECHANISMS; LIPIDS
AB A gap in our understanding of the beneficial systemic responses to dietary constituents nitrate (NO3-), nitrite (NO2-) and conjugated linoleic acid (cLA) is the identification of the downstream metabolites that mediate their actions. To examine these reactions in a clinical context, investigational drug preparations of N-15-labeled NO3- and NO2- were orally administered to healthy humans with and without cLA. Mass spectrometry analysis of plasma and urine indicated that the nitrating species nitrogen dioxide was formed and reacted with the olefinic carbons of unsaturated fatty acids to yield the electrophilic fatty acid, nitro-cLA (NO2-cLA). These species mediate the post-translational modification (PTM) of proteins via reversible Michael addition with nucleophilic amino acids. The PTM of critical target proteins by electrophilic lipids has been described as a sensing mechanism that regulates adaptive cellular responses, but little is known about the endogenous generation of fatty acid nitroalkenes and their metabolites. We report that healthy humans consuming N-15-labeled NO3- or NO2-, with and without cLA supplementation, produce (NO2)-N-15-cLA and corresponding metabolites that are detected in plasma and urine. These data support that the dietary constituents NO3-, NO2- and cLA promote the further generation of secondary electrophilic lipid products that are absorbed into the circulation at concentrations sufficient to exert systemic effects before being catabolized or excreted. (C) 2015 Elsevier Inc. All rights reserved.
C1 [Delmastro-Greenwood, Meghan; Vitturi, Dario A.; Salvatore, Sonia R.; Shiva, Sruti; Schopfer, Francisco J.; Freeman, Bruce A.; Wendell, Stacy Gelhaus] Univ Pittsburgh, Dept Pharmacol & Chem Biol, Pittsburgh, PA 15261 USA.
[Hughan, Kara S.; Shiva, Sruti; Schopfer, Francisco J.; Gladwin, Mark T.; Freeman, Bruce A.; Wendell, Stacy Gelhaus] Univ Pittsburgh, Pittsburgh Heart Lung Blood & Vasc Med Inst, Pittsburgh, PA 15261 USA.
[Grimes, George; Potti, Gopal] NIH, Pharmaceut Dev Sect, Dept Pharm, Ctr Clin, Bethesda, MD 20892 USA.
RP Freeman, BA (reprint author), Univ Pittsburgh, Sch Med, Dept Pharmacol & Chem Biol, 200 Lothrop St,Biomed Sci Tower E1340, Pittsburgh, PA 15261 USA.
EM freerad@pitt.edu; gstacy@pitt.edu
OI Vitturi, Dario/0000-0003-0354-4567
FU NIH [R01-HL058115, R01-HL64937, P01-HL103455, AT00682, K12-HD052892];
Cochrane Weber Fund of Children's Hospital of Pittsburgh of UPMC;
Vascular Medicine Institute/CTSI Pilot Project Program in Hemostasis &
Vascular Biology
FX The authors thank Ram Agarwal, Deborah Sperling and Judith Starling for
formulating 15NOx, Nydia Chien and Suchitra Barge for their
IRB and regulatory assistance and Nicole Helbling and Alex Despines for
trial implementation. This work was supported by NIH grants
R01-HL058115, R01-HL64937 (BF), P01-HL103455 (MG, BF), AT00682 (FJS),
K12-HD052892 (KSH), the Cochrane Weber Fund of Children's Hospital of
Pittsburgh of UPMC and the Vascular Medicine Institute/CTSI Pilot
Project Program in Hemostasis & Vascular Biology. FJS and BAF
acknowledge interest in Complexa, Inc. MTG is co-inventor on a US
Government Patent for the use of nitrite salts for cardiovascular
indications (IND # 70,411) and has received royalties from the US
Government.
NR 42
TC 6
Z9 6
U1 1
U2 10
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 DEC
PY 2015
VL 89
BP 333
EP 341
DI 10.1016/j.freeradbiomed.2015.07.149
PG 9
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA CY4CI
UT WOS:000366355800031
PM 26385079
ER
PT J
AU Jiao, S
Peters, U
Berndt, S
Bezieau, S
Brenner, H
Campbell, PT
Chan, AT
Chang-Claude, J
Lemire, M
Newcomb, PA
Potter, JD
Slattery, ML
Woods, MO
Hsu, L
AF Jiao, Shuo
Peters, Ulrike
Berndt, Sonja
Bezieau, Stephane
Brenner, Hermann
Campbell, Peter T.
Chan, Andrew T.
Chang-Claude, Jenny
Lemire, Mathieu
Newcomb, Polly A.
Potter, John D.
Slattery, Martha L.
Woods, Michael O.
Hsu, Li
TI Powerful Set-Based Gene-Environment Interaction Testing Framework for
Complex Diseases
SO GENETIC EPIDEMIOLOGY
LA English
DT Article
DE G x E screening statistics; eSBERUA; rare variants; GWAS
ID GENOME-WIDE ASSOCIATION; RARE-VARIANT ASSOCIATION; COLORECTAL-CANCER;
COMMON VARIANTS; BLADDER-CANCER; MARKER-SET; SUSCEPTIBILITY;
INDEPENDENCE; TRAITS; MODELS
AB Identification of gene-environment interaction (G x E) is important in understanding the etiology of complex diseases. Based on our previously developed Set Based gene EnviRonment InterAction test (SBERIA), in this paper we propose a powerful framework for enhanced set-based G x E testing (eSBERIA). The major challenge of signal aggregation within a set is how to tell signals from noise. eSBERIA tackles this challenge by adaptively aggregating the interaction signals within a set weighted by the strength of the marginal and correlation screening signals. eSBERIA then combines the screening-informed aggregate test with a variance component test to account for the residual signals. Additionally, we develop a case-only extension for eSBERIA (coSBERIA) and an existing set-based method, which boosts the power not only by exploiting the G-E independence assumption but also by avoiding the need to specify main effects for a large number of variants in the set. Through extensive simulation, we show that coSBERIA and eSBERIA are considerably more powerful than existing methods within the case-only and the case-control method categories across a wide range of scenarios. We conduct a genome-wide G x E search by applying our methods to Illumina HumanExome Beadchip data of 10,446 colorectal cancer cases and 10,191 controls and identify two novel interactions between nonsteroidal anti-inflammatory drugs (NSAIDs) and MINK1 and PTCHD3. (C) 2015 Wiley Periodicals, Inc.
C1 [Jiao, Shuo; Peters, Ulrike; Newcomb, Polly A.; Potter, John D.; Hsu, Li] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA.
[Berndt, Sonja] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Bezieau, Stephane] CHU Nantes, Serv Genet Med, F-44035 Nantes 01, France.
[Brenner, Hermann] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany.
[Brenner, Hermann] German Canc Consortium DKTK, Heidelberg, Germany.
[Campbell, Peter T.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA.
[Chan, Andrew T.] Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA.
[Chan, Andrew T.] Harvard Univ, Sch Med, Boston, MA USA.
[Chang-Claude, Jenny] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany.
[Lemire, Mathieu] Ontario Inst Canc Res, Toronto, ON, Canada.
[Newcomb, Polly A.] Univ Washington, Sch Publ Hlth, Seattle, WA 98195 USA.
[Potter, John D.] Massey Univ, Ctr Publ Hlth Res, Wellington, New Zealand.
[Slattery, Martha L.] Univ Utah, Hlth Sci Ctr, Dept Internal Med, Salt Lake City, UT USA.
[Woods, Michael O.] Mem Univ Newfoundland, Discipline Genet, St John, NF, Canada.
RP Hsu, L (reprint author), Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, 1100 Fairview Ave N,Mailstop M2-B500, Seattle, WA 98109 USA.
EM lih@fredhutch.org
RI Brenner, Hermann/B-4627-2017;
OI Brenner, Hermann/0000-0002-6129-1572; Bezieau,
stephane/0000-0003-0095-1319; Potter, John/0000-0001-5439-1500
FU NCI NIH HHS [P01 CA053996, K05 CA152715, P30 CA015704, R01 CA059045, R21
CA191312, U01 CA137088, U01 CA164930]; NIA NIH HHS [R01 AG014358]; NIH
HHS [S10 OD020069]
NR 29
TC 1
Z9 1
U1 0
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0741-0395
EI 1098-2272
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD DEC
PY 2015
VL 39
IS 8
BP 609
EP 618
DI 10.1002/gepi.21908
PG 10
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA CY7RA
UT WOS:000366605200002
PM 26095235
ER
PT J
AU Asimit, JL
Panoutsopoulou, K
Wheeler, E
Berndt, SI
Cordell, HJ
Morris, AP
Zeggini, E
Barroso, I
AF Asimit, Jennifer L.
Panoutsopoulou, Kalliope
Wheeler, Eleanor
Berndt, Sonja I.
Cordell, Heather J.
Morris, Andrew P.
Zeggini, Eleftheria
Barroso, Ines
CA GIANT Consortium
ArcOGEN Consortium
TI A Bayesian Approach to the Overlap Analysis of Epidemiologically Linked
Traits
SO GENETIC EPIDEMIOLOGY
LA English
DT Article
DE Bayes' factor; P-value; obesity; osteoarthritis; overlap analysis;
threshold calibration
ID GENOME-WIDE ASSOCIATION; GENETIC ASSOCIATION; SUSCEPTIBILITY LOCI;
IDENTIFICATION; OSTEOARTHRITIS; IMPUTATION; VARIANTS; CANCER; TOOL
AB Diseases often cooccur in individuals more often than expected by chance, and may be explained by shared underlying genetic etiology. A common approach to genetic overlap analyses is to use summary genome-wide association study data to identify single-nucleotide polymorphisms (SNPs) that are associated with multiple traits at a selected P-value threshold. However, P-values do not account for differences in power, whereas Bayes' factors (BFs) do, and may be approximated using summary statistics. We use simulation studies to compare the power of frequentist and Bayesian approaches with overlap analyses, and to decide on appropriate thresholds for comparison between the two methods. It is empirically illustrated that BFs have the advantage over P-values of a decreasing type I error rate as study size increases for single-disease associations. Consequently, the overlap analysis of traits from different-sized studies encounters issues in fair P-value threshold selection, whereas BFs are adjusted automatically. Extensive simulations show that Bayesian overlap analyses tend to have higher power than those that assess association strength with P-values, particularly in low-power scenarios. Calibration tables between BFs and P-values are provided for a range of sample sizes, as well as an approximation approach for sample sizes that are not in the calibration table. Although P-values are sometimes thought more intuitive, these tables assist in removing the opaqueness of Bayesian thresholds and may also be used in the selection of a BF threshold to meet a certain type I error rate. An application of our methods is used to identify variants associated with both obesity and osteoarthritis. Published 2015 Wiley Periodicals, Inc.
C1 [Asimit, Jennifer L.; Panoutsopoulou, Kalliope; Wheeler, Eleanor; Zeggini, Eleftheria; Barroso, Ines] Wellcome Trust Sanger Inst, Cambridge CB10 1HH, England.
[Berndt, Sonja I.] NCI, Div Canc Epidemiol & Genet, US Natl Inst Hlth, Bethesda, MD 20892 USA.
[Cordell, Heather J.] Newcastle Univ, Inst Med Genet, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England.
[Morris, Andrew P.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.
[Morris, Andrew P.] Univ Liverpool, Dept Biostat, Liverpool L69 3BX, Merseyside, England.
RP Asimit, JL (reprint author), Wellcome Trust Sanger Inst, Morgan Bldg,Wellcome Trust Genome Campus, Cambridge CB10 1HH, England.
EM ja11@sanger.ac.uk
OI Zeggini, Eleftheria/0000-0003-4238-659X; Asimit,
Jennifer/0000-0002-4857-2249; Wheeler, Eleanor/0000-0002-8616-6444
FU Arthritis Research UK; Medical Research Council [MR/K021486/1]; Wellcome
Trust [087436, WT098051]
NR 27
TC 1
Z9 1
U1 1
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0741-0395
EI 1098-2272
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD DEC
PY 2015
VL 39
IS 8
BP 624
EP 634
DI 10.1002/gepi.21919
PG 11
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA CY7RA
UT WOS:000366605200004
PM 26411566
ER
PT J
AU Amankwah, EK
Lin, HY
Tyrer, JP
Lawrenson, K
Dennis, J
Chornokur, G
Aben, KKH
Anton-Culver, H
Antonenkova, N
Bruinsma, F
Bandera, EV
Bean, YT
Beckmann, MW
Bisogna, M
Bjorge, L
Bogdanova, N
Brinton, LA
Brooks-Wilson, A
Bunker, CH
Butzow, R
Campbell, IG
Carty, K
Chen, ZH
Chen, YA
Chang-Claude, J
Cook, LS
Cramer, DW
Cunningham, JM
Cybulski, C
Dansonka-Mieszkowska, A
Du Bois, A
Despierre, E
Dicks, E
Doherty, JA
Doerk, T
Duerst, M
Easton, DF
Eccles, DM
Edwards, RP
Ekici, AB
Fasching, PA
Fridley, BL
Gao, YT
Gentry-Maharaj, A
Giles, GG
Glasspool, R
Goodman, MT
Gronwald, J
Harrington, P
Harter, P
Hasmad, HN
Hein, A
Heitz, F
Hildebrandt, MAT
Hillemanns, P
Hogdall, CK
Hogdall, E
Hosono, S
Iversen, ES
Jakubowska, A
Jensen, A
Ji, BT
Karlan, BY
Jim, H
Kellar, M
Kiemeney, LA
Krakstad, C
Kjaer, SK
Kupryjanczyk, J
Lambrechts, D
Lambrechts, S
Le, ND
Lee, AW
Lele, S
Leminen, A
Lester, J
Levine, DA
Liang, D
Lim, BK
Lissowska, J
Lu, K
Lubinski, J
Lundvall, L
Massuger, LFAG
Matsuo, K
McGuire, V
McLaughlin, JR
McNeish, I
Menon, U
Milne, RL
Modugno, F
Moysich, KB
Ness, RB
Nevanlinna, H
Eilber, U
Odunsi, K
Olson, SH
Orlow, I
Orsulic, S
Weber, RP
Paul, J
Pearce, CL
Pejovic, T
Pelttari, LM
Permuth-Wey, J
Pike, MC
Poole, EM
Risch, HA
Rosen, B
Rossing, MA
Rothstein, JH
Rudolph, A
Runnebaum, IB
Rzepecka, IK
Salvesen, HB
Schernhammer, E
Schwaab, I
Shu, XO
Shvetsov, YB
Siddiqui, N
Sieh, W
Song, HL
Southey, MC
Spiewankiewicz, B
Sucheston-Campbell, L
Teo, SH
Terry, KL
Thompson, PJ
Thomsen, L
Tangen, IL
Tworoger, SS
Van Altena, AM
Vierkant, RA
Vergote, I
Walsh, CS
Wang-Gohrke, S
Wentzensen, N
Whittemore, AS
Wicklund, KG
Wilkens, LR
Wu, AH
Wu, XF
Woo, YL
Yang, H
Zheng, W
Ziogas, A
Kelemen, LE
Berchuck, A
Chenevix-Trench, G
Grp, AM
Schildkraut, JM
Ramus, SJ
Goode, EL
Monteiro, ANA
Gayther, SA
Narod, SA
Pharoah, PDP
Sellers, TA
Phelan, CM
AF Amankwah, Ernest K.
Lin, Hui-Yi
Tyrer, Jonathan P.
Lawrenson, Kate
Dennis, Joe
Chornokur, Ganna
Aben, Katja K. H.
Anton-Culver, Hoda
Antonenkova, Natalia
Bruinsma, Fiona
Bandera, Elisa V.
Bean, Yukie T.
Beckmann, Matthias W.
Bisogna, Maria
Bjorge, Line
Bogdanova, Natalia
Brinton, Louise A.
Brooks-Wilson, Angela
Bunker, Clareann H.
Butzow, Ralf
Campbell, Ian G.
Carty, Karen
Chen, Zhihua
Chen, Y. Ann
Chang-Claude, Jenny
Cook, Linda S.
Cramer, Daniel W.
Cunningham, Julie M.
Cybulski, Cezary
Dansonka-Mieszkowska, Agnieszka
Du Bois, Andreas
Despierre, Evelyn
Dicks, Ed
Doherty, Jennifer A.
Doerk, Thilo
Duerst, Matthias
Easton, Douglas F.
Eccles, Diana M.
Edwards, Robert P.
Ekici, Arif B.
Fasching, Peter A.
Fridley, Brooke L.
Gao, Yu-Tang
Gentry-Maharaj, Aleksandra
Giles, Graham G.
Glasspool, Rosalind
Goodman, Marc T.
Gronwald, Jacek
Harrington, Patricia
Harter, Philipp
Hasmad, Hanis N.
Hein, Alexander
Heitz, Florian
Hildebrandt, Michelle A. T.
Hillemanns, Peter
Hogdall, Claus K.
Hogdall, Estrid
Hosono, Satoyo
Iversen, Edwin S.
Jakubowska, Anna
Jensen, Allan
Ji, Bu-Tian
Karlan, Beth Y.
Jim, Heather
Kellar, Melissa
Kiemeney, Lambertus A.
Krakstad, Camilla
Kjaer, Susanne K.
Kupryjanczyk, Jolanta
Lambrechts, Diether
Lambrechts, Sandrina
Le, Nhu D.
Lee, Alice W.
Lele, Shashi
Leminen, Arto
Lester, Jenny
Levine, Douglas A.
Liang, Dong
Lim, Boon Kiong
Lissowska, Jolanta
Lu, Karen
Lubinski, Jan
Lundvall, Lene
Massuger, Leon F. A. G.
Matsuo, Keitaro
McGuire, Valerie
McLaughlin, John R.
McNeish, Ian
Menon, Usha
Milne, Roger L.
Modugno, Francesmary
Moysich, Kirsten B.
Ness, Roberta B.
Nevanlinna, Heli
Eilber, Ursula
Odunsi, Kunle
Olson, Sara H.
Orlow, Irene
Orsulic, Sandra
Weber, Rachel Palmieri
Paul, James
Pearce, Celeste L.
Pejovic, Tanja
Pelttari, Liisa M.
Permuth-Wey, Jennifer
Pike, Malcolm C.
Poole, Elizabeth M.
Risch, Harvey A.
Rosen, Barry
Rossing, Mary Anne
Rothstein, Joseph H.
Rudolph, Anja
Runnebaum, Ingo B.
Rzepecka, Iwona K.
Salvesen, Helga B.
Schernhammer, Eva
Schwaab, Ira
Shu, Xiao-Ou
Shvetsov, Yurii B.
Siddiqui, Nadeem
Sieh, Weiva
Song, Honglin
Southey, Melissa C.
Spiewankiewicz, Beata
Sucheston-Campbell, Lara
Teo, Soo-Hwang
Terry, Kathryn L.
Thompson, Pamela J.
Thomsen, Lotte
Tangen, Ingvild L.
Tworoger, Shelley S.
Van Altena, Anne M.
Vierkant, Robert A.
Vergote, Ignace
Walsh, Christine S.
Wang-Gohrke, Shan
Wentzensen, Nicolas
Whittemore, Alice S.
Wicklund, Kristine G.
Wilkens, Lynne R.
Wu, Anna H.
Wu, Xifeng
Woo, Yin-Ling
Yang, Hannah
Zheng, Wei
Ziogas, Argyrios
Kelemen, Linda E.
Berchuck, Andrew
Chenevix-Trench, Georgia
Grp, Aocs Management
Schildkraut, Joellen M.
Ramus, Susan J.
Goode, Ellen L.
Monteiro, Alvaro N. A.
Gayther, Simon A.
Narod, Steven A.
Pharoah, Paul D. P.
Sellers, Thomas A.
Phelan, Catherine M.
TI Epithelial-Mesenchymal Transition (EMT) Gene Variants and Epithelial
Ovarian Cancer (EOC) Risk
SO GENETIC EPIDEMIOLOGY
LA English
DT Article
DE ovarian cancer; epithelial-mesenchymal transition; single-nucleotide
polymorphisms
ID SINGLE-NUCLEOTIDE POLYMORPHISMS; LUNG-CANCER; NEVER SMOKERS;
SUSCEPTIBILITY; NEUROPILIN-1; SURVIVAL; DISEASE; METAANALYSIS;
GLYPICANS; ONCOGENES
AB Epithelial-mesenchymal transition (EMT) is a process whereby epithelial cells assume mesenchymal characteristics to facilitate cancer metastasis. However, EMT also contributes to the initiation and development of primary tumors. Prior studies that explored the hypothesis that EMT gene variants contribute to epithelial ovarian carcinoma (EOC) risk have been based on small sample sizes and none have sought replication in an independent population. We screened 15,816 single-nucleotide polymorphisms (SNPs) in 296 genes in a discovery phase using data from a genome-wide association study of EOC among women of European ancestry (1,947 cases and 2,009 controls) and identified 793 variants in 278 EMT-related genes that were nominally (P < 0.05) associated with invasive EOC. These SNPs were then genotyped in a larger study of 14,525 invasive-cancer patients and 23,447 controls. A P-value < 0.05 and a false discovery rate (FDR) < 0.2 were considered statistically significant. In the larger dataset, GPC6/GPC5 rs17702471 was associated with the endometrioid subtype among Caucasians (odds ratio (OR) = 1.16, 95% CI = 1.07-1.25, P = 0.0003, FDR = 0.19), whereas F8 rs7053448 (OR = 1.69, 95% CI = 1.27-2.24, P = 0.0003, FDR = 0.12), F8 rs7058826 (OR = 1.69, 95% CI = 1.27-2.24, P = 0.0003, FDR = 0.12), and CAPN13 rs1983383 (OR = 0.79, 95% CI = 0.69-0.90, P = 0.0005, FDR = 0.12) were associated with combined invasive EOC among Asians. In silico functional analyses revealed that GPC6/GPC5 rs17702471 coincided with DNA regulatory elements. These results suggest that EMT gene variants do not appear to play a significant role in the susceptibility to EOC. (C) 2015 Wiley Periodicals, Inc.
C1 [Amankwah, Ernest K.; Chornokur, Ganna; Permuth-Wey, Jennifer; Sellers, Thomas A.; Phelan, Catherine M.] H Lee Moffitt Canc Ctr & Res Inst, Dept Canc Epidemiol, Tampa, FL 33612 USA.
[Amankwah, Ernest K.] All Childrens Hosp Johns Hopkins Med, Clin & Translat Res Org, St Petersburg, FL USA.
[Lin, Hui-Yi; Chen, Zhihua; Chen, Y. Ann; Monteiro, Alvaro N. A.] H Lee Moffitt Canc Ctr & Res Inst, Dept Biostat & Bioinformat, Tampa, FL USA.
[Tyrer, Jonathan P.; Dennis, Joe] Univ Cambridge, Strangeways Res Lab, Dept Publ Hlth & Primary Care, Ctr Canc Epidemiol, Cambridge, England.
[Lawrenson, Kate; Lee, Alice W.; Pearce, Celeste L.; Pike, Malcolm C.; Wu, Anna H.; Ramus, Susan J.; Gayther, Simon A.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Norris Comprehens Canc Ctr, Los Angeles, CA 90033 USA.
[Aben, Katja K. H.; Kiemeney, Lambertus A.] Radboud Univ Nijmegen, Med Ctr, Radboud Inst Hlth Sci, Dept Hlth Evidence, NL-6525 ED Nijmegen, Netherlands.
[Aben, Katja K. H.] Comprehens Canc Ctr Netherlands, Nijmegen, Netherlands.
[Anton-Culver, Hoda; Ziogas, Argyrios] Univ Calif Irvine, Sch Med, Dept Epidemiol, UCI Ctr Canc Genet Res & Prevent,Genet Epidemiol, Irvine, CA 92717 USA.
[Antonenkova, Natalia] Byelorussian Inst Oncol & Med Radiol Aleksandrov, Minsk, Byelarus.
[Bruinsma, Fiona; Giles, Graham G.; Milne, Roger L.] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Australia.
[Bandera, Elisa V.] Rutgers Canc Inst New Jersey, Canc Prevent & Control, New Brunswick, NJ USA.
[Bean, Yukie T.; Kellar, Melissa; Pejovic, Tanja] Oregon Hlth & Sci Univ, Dept Obstet & Gynecol, Portland, OR 97201 USA.
[Bean, Yukie T.; Kellar, Melissa; Pejovic, Tanja] Oregon Hlth & Sci Univ, Knight Canc Inst, Portland, OR 97201 USA.
[Beckmann, Matthias W.; Fasching, Peter A.; Hein, Alexander] Univ Erlangen Nurnberg, Univ Hosp Erlangen, Dept Gynecol & Obstet, Erlangen Nuremberg Comprehens Canc Ctr, Erlangen Emn, Germany.
[Bisogna, Maria; Levine, Douglas A.] Mem Sloan Kettering Canc Ctr, Dept Surg, Gynecol Serv, New York, NY 10021 USA.
[Bjorge, Line; Krakstad, Camilla; Salvesen, Helga B.; Tangen, Ingvild L.] Haukeland Hosp, Dept Gynecol & Obstet, N-5021 Bergen, Norway.
[Bjorge, Line; Krakstad, Camilla; Salvesen, Helga B.; Tangen, Ingvild L.] Univ Bergen, Dept Clin Med, Ctr Canc Biomarkers, Bergen, Norway.
[Bogdanova, Natalia; Doerk, Thilo; Hillemanns, Peter] Hannover Med Sch, Radiat Oncol Res Unit, Hannover, Germany.
[Brinton, Louise A.; Ji, Bu-Tian; Wentzensen, Nicolas; Yang, Hannah] Natl Canc Inst, Div Canc Epidemiol & Genet, Bethesda, MD USA.
[Brooks-Wilson, Angela] BC Canc Agcy, Canadas Michael Smith Genome Sci Ctr, Vancouver, BC, Canada.
[Brooks-Wilson, Angela] Simon Fraser Univ, Dept Biomed Physiol & Kinesiol, Burnaby, BC V5A 1S6, Canada.
[Bunker, Clareann H.; Modugno, Francesmary] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA.
[Butzow, Ralf; Leminen, Arto; Nevanlinna, Heli; Pelttari, Liisa M.] Univ Helsinki, Cent Hosp, Dept Obstet & Gynecol, Helsinki, Hus, Finland.
[Butzow, Ralf] Univ Helsinki, Cent Hosp, Dept Pathol, Helsinki, Finland.
[Campbell, Ian G.] Peter MacCallum Canc Inst, Div Res, Canc Genet Lab, East Melbourne, Australia.
[Campbell, Ian G.; Southey, Melissa C.] Univ Melbourne, Dept Pathol, Parkville, Vic 3052, Australia.
[Campbell, Ian G.] Univ Melbourne, Sir Peter MacCallum Dept Oncol, Parkville, Vic 3052, Australia.
[Carty, Karen; Siddiqui, Nadeem] Glasgow Royal Infirm, Dept Gynaecol Oncol, Glasgow G4 0SF, Lanark, Scotland.
[Carty, Karen; Glasspool, Rosalind; McNeish, Ian; Paul, James] Beatson West Scotland Canc Ctr, CRUK Clin Trials Unit, Glasgow, Lanark, Scotland.
[Chang-Claude, Jenny; Eilber, Ursula; Rudolph, Anja; Wang-Gohrke, Shan] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany.
[Cook, Linda S.] Univ New Mexico, Dept Internal Med, Div Epidemiol & Biostat, Albuquerque, NM 87131 USA.
[Cramer, Daniel W.; Terry, Kathryn L.; Tworoger, Shelley S.] Brigham & Womens Hosp, Obstet & Gynecol Ctr, Boston, MA 02115 USA.
[Cramer, Daniel W.; Terry, Kathryn L.; Tworoger, Shelley S.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Cunningham, Julie M.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA.
[Cybulski, Cezary; Gronwald, Jacek; Jakubowska, Anna; Lubinski, Jan] Pomeranian Med Univ, Dept Genet & Pathol, Int Hereditary Canc Ctr, Szczecin, Poland.
[Dansonka-Mieszkowska, Agnieszka; Kupryjanczyk, Jolanta; Rzepecka, Iwona K.] Maria Sklodowska Curie Mem Canc Ctr, Dept Pathol, Warsaw, Poland.
[Dansonka-Mieszkowska, Agnieszka; Kupryjanczyk, Jolanta; Rzepecka, Iwona K.] Inst Oncol, Warsaw, Poland.
[Du Bois, Andreas; Harter, Philipp; Heitz, Florian] Knappschaft GmbH, Evang Huyssens Stiftung, Kliniken Essen Mitte, Dept Gynaecol & Gynaecol Oncol, Essen, Germany.
[Du Bois, Andreas; Harter, Philipp; Heitz, Florian] Dr Horst Schmidt Kliniken Wiesbaden, Dept Gynaecol & Gynaecol Oncol, Wiesbaden, Germany.
[Despierre, Evelyn; Lambrechts, Sandrina; Vergote, Ignace] Katholieke Univ Leuven, Univ Hosp Leuven, Leuven Canc Inst, Div Gynecol, Leuven, Belgium.
[Dicks, Ed; Harrington, Patricia; Song, Honglin] Univ Cambridge, Strangeways Res Lab, Dept Oncol, Ctr Canc Epidemiol, Cambridge, England.
[Doherty, Jennifer A.] Dartmouth Coll, Hitchcock Med Ctr, Dartmouth Med Sch, Sect Biostat & Epidemiol,Dept Community & Family, Hanover, NH 03756 USA.
[Doherty, Jennifer A.; Rossing, Mary Anne; Wicklund, Kristine G.] Univ Washington, Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Program Epidemiol, Seattle, WA 98195 USA.
[Duerst, Matthias; Runnebaum, Ingo B.] Univ Jena, Dept Gynecol, Jena, Germany.
[Easton, Douglas F.] Univ Cambridge, Dept Oncol, Ctr Canc Genet Epidemiol, Cambridge, England.
[Easton, Douglas F.] Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge, England.
[Eccles, Diana M.] Princess Anne Hosp, Wessex Clin Genet Serv, Southampton, Hants, England.
[Edwards, Robert P.] Univ Pittsburgh, Div Gynecol Oncol, Dept Obstet Gynecol RS, Ovarian Canc Ctr Excellence, Pittsburgh, PA USA.
[Ekici, Arif B.] Univ Erlangen Nurnberg, Univ Hosp Erlangen, Inst Human Genet, Erlangen, Germany.
[Fasching, Peter A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Hematol & Oncol, Los Angeles, CA 90095 USA.
[Fridley, Brooke L.] Univ Kansas, Med Ctr, Biostat & Informat Shared Resource, Kansas City, KS 66103 USA.
[Gao, Yu-Tang] Shanghai Canc Inst, Dept Epidemiol, Shanghai, Peoples R China.
[Gentry-Maharaj, Aleksandra; Menon, Usha] UCL EGA Inst Womens Hlth, Womens Canc, London, England.
[Giles, Graham G.; Milne, Roger L.] Univ Melbourne, Sch Populat & Global Hlth, Ctr Epidemiol & Biostat, Melbourne, Australia.
[Goodman, Marc T.; Thompson, Pamela J.] Cedars Sinai Med Ctr, Samuel Oschin Comprehens Canc Inst, Canc Prevent & Control, Los Angeles, CA 90048 USA.
[Goodman, Marc T.; Thompson, Pamela J.] Cedars Sinai Med Ctr, Dept Biomed Sci, Community & Populat Hlth Res Inst, Los Angeles, CA 90048 USA.
[Hasmad, Hanis N.; Teo, Soo-Hwang] Sime Darby Med Ctr, Canc Res Initiat Fdn, Subang Jaya, Malaysia.
[Hildebrandt, Michelle A. T.; Wu, Xifeng] Univ Texas MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA.
[Hogdall, Claus K.; Kjaer, Susanne K.; Lundvall, Lene] Univ Copenhagen, Rigshosp, Dept Gynaecol, DK-2100 Copenhagen, Denmark.
[Hogdall, Estrid; Jensen, Allan; Kjaer, Susanne K.] Danish Canc Soc Res Ctr, Dept Virus Lifestyle & Genes, Copenhagen, Denmark.
[Hogdall, Estrid] Univ Copenhagen, Herlev Hosp, Dept Pathol, Mol Unit, Copenhagen, Denmark.
[Hosono, Satoyo; Matsuo, Keitaro] Aichi Canc Ctr Res Inst, Div Epidemiol & Prevent, Nagoya, Aichi, Japan.
[Iversen, Edwin S.] Duke Univ, Dept Stat, Durham, NC USA.
[Karlan, Beth Y.; Lester, Jenny; Orsulic, Sandra; Walsh, Christine S.] Cedars Sinai Med Ctr, Inst Canc, Womens Canc Program Samuel Oschin Comprehens, Los Angeles, CA 90048 USA.
[Jim, Heather] H Lee Moffitt Canc Ctr & Res Inst, Dept Hlth Outcomes & Behav, Tampa, FL USA.
[Lambrechts, Diether] Univ Leuven, VIB, Vesalius Res Ctr, Leuven, Belgium.
[Lambrechts, Diether] Univ Leuven, Dept Oncol, Lab Translat Genet, Leuven, Belgium.
[Le, Nhu D.] BC Canc Agcy, Canc Control Res, Vancouver, BC, Canada.
[Lele, Shashi; Moysich, Kirsten B.; Sucheston-Campbell, Lara] Roswell Pk Canc Inst, Dept Canc Prevent & Control, Buffalo, NY 14263 USA.
[Liang, Dong] Texas So Univ, Coll Pharm & Hlth Sci, Houston, TX 77004 USA.
[Lim, Boon Kiong; Woo, Yin-Ling] Univ Malaya, Med Ctr, Dept Obstet & Gynaecol, Kuala Lumpur, Malaysia.
[Lissowska, Jolanta] M Sklodowska Curie Mem Canc Ctr, Dept Canc Epidemiol & Prevent, Warsaw, Poland.
[Lissowska, Jolanta] Inst Oncol, Warsaw, Poland.
[Lu, Karen] Univ Texas MD Anderson Canc Ctr, Dept Gynecol Oncol, Houston, TX 77030 USA.
[Massuger, Leon F. A. G.; Van Altena, Anne M.] Radboud Inst Mol Life Sci, Radboud Univ Med Ctr, Nijmegen, Netherlands.
[McGuire, Valerie; Rothstein, Joseph H.; Sieh, Weiva; Whittemore, Alice S.] Stanford Univ, Sch Med, Dept Hlth Res & Policy Epidemiol, Stanford, CA 94305 USA.
[McLaughlin, John R.] Publ Hlth Ontario, Toronto, ON, Canada.
[Modugno, Francesmary] Univ Pittsburgh, Inst Canc, Womens Canc Res Program, Magee Womens Res Inst, Pittsburgh, PA USA.
[Modugno, Francesmary] Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA.
[Modugno, Francesmary] Univ Pittsburgh, Sch Med, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA USA.
[Ness, Roberta B.] Univ Texas Houston, Sch Publ Hlth, Houston, TX USA.
[Odunsi, Kunle] Roswell Pk Canc Inst, Dept Gynecol Oncol, Buffalo, NY 14263 USA.
[Olson, Sara H.; Orlow, Irene; Pike, Malcolm C.] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA.
[Weber, Rachel Palmieri] Duke Univ, Med Ctr, Dept Community & Family Med, Durham, NC USA.
[Pearce, Celeste L.] Univ Michigan, Dept Epidemiol, Ann Arbor, MI 48109 USA.
[Poole, Elizabeth M.; Schernhammer, Eva] Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA.
[Poole, Elizabeth M.; Schernhammer, Eva] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Poole, Elizabeth M.; Schernhammer, Eva; Terry, Kathryn L.; Tworoger, Shelley S.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Risch, Harvey A.] Yale Univ, Sch Publ Hlth, Dept Chron Dis Epidemiol, New Haven, CT USA.
[Rosen, Barry] Princess Margaret Hosp, Dept Gynecology Oncol, Toronto, ON M4X 1K9, Canada.
[Rosen, Barry] Univ Toronto, Fac Med, Dept Obstet & Gynecol, Toronto, ON, Canada.
[Lele, Shashi; Moysich, Kirsten B.; Sucheston-Campbell, Lara] Inst Human Genet & Anthropol, Wiesbaden, Germany.
[Shu, Xiao-Ou] Vanderbilt Univ, Sch Med, Ingram Canc Ctr, Epidemiol Ctr & Vanderbilt, Nashville, TN 37235 USA.
[Shvetsov, Yurii B.; Wilkens, Lynne R.] Univ Hawaii, Canc Epidemiol Program, Honolulu, HI 96822 USA.
[Spiewankiewicz, Beata] Inst Oncol, Dept Gynecol Oncol, Warsaw, Poland.
[Teo, Soo-Hwang] Univ Malaya, Med Ctr, Kuala Lumpur, Malaysia.
[Thomsen, Lotte] Univ Copenhagen, Rigshosp, Dept Pathol, DK-2100 Copenhagen, Denmark.
[Vierkant, Robert A.] Mayo Clin, Div Biomed Stat & Informat, Dept Hlth Sci Res, Rochester, MN USA.
[Zheng, Wei] Vanderbilt Univ, Sch Med, Vanderbilt Epidemiol Ctr, Nashville, TN 37235 USA.
[Kelemen, Linda E.] Med Univ S Carolina, Dept Publ Hlth Sci, Charleston, SC 29425 USA.
[Berchuck, Andrew] Duke Univ, Med Ctr, Dept Obstet & Gynecol, Durham, NC USA.
[Chenevix-Trench, Georgia; Grp, Aocs Management] QIMR Berghofer Med Res Inst, Brisbane, Qld, Australia.
[Chenevix-Trench, Georgia; Grp, Aocs Management] Peter MacCallum Canc Ctr, East Melbourne, Australia.
[Schildkraut, Joellen M.] Duke Canc Inst, Canc Prevent Detect & Control Res Program, Durham, NC USA.
[Goode, Ellen L.] Mayo Clin, Div Epidemiol, Dept Hlth Sci Res, Rochester, MN USA.
[Narod, Steven A.] Univ Toronto, Womens Coll Res Inst, Toronto, ON, Canada.
RP Phelan, CM (reprint author), H Lee Moffitt Canc Ctr & Res Inst, Dept Canc Epidemiol, 12902 Magnolia Dr, Tampa, FL 33612 USA.
EM catherine.phelan@moffitt.org
RI van Altena, Anne/B-9824-2016; Brooks-Wilson, Angela/E-9399-2012; Teo,
Soo-hwang/H-2353-2014; Aben, Katja/G-9686-2016; Hein,
Alexander/F-6999-2010; Dork, Thilo/J-8620-2012; Gronwald,
Jacek/A-4576-2017; Bjorge, Line/C-1307-2017; salvesen,
Helga/C-1187-2017;
OI Matsuo, Keitaro/0000-0003-1761-6314; Giles, Graham/0000-0003-4946-9099;
Brooks-Wilson, Angela/0000-0003-1009-6408; Aben,
Katja/0000-0002-0214-2147; Hein, Alexander/0000-0003-2601-3398;
Gronwald, Jacek/0000-0002-3643-2871; Bjorge, Line/0000-0002-0240-2770;
salvesen, Helga/0000-0002-4438-8831; Glasspool,
Rosalind/0000-0002-5000-1680; Ramus, Susan/0000-0003-0005-7798;
Krakstad, Camilla/0000-0002-0174-8139
FU Canadian Institutes of Health Research [MOP-86727]; Cancer Research UK
[10124, C490/A10119, C490/A10124, C490/A6187]; NCI NIH HHS [K22
CA138563, 1K99CA184415-01, K07 CA092044, K07 CA095666, K07 CA143047, K99
CA184415, N01 CN025403, N01 PC035137, N01 PC067010, P01 CA017054, P01
CA087969, P30 CA008748, P30 CA014089, P30 CA015083, P30 CA016056, P30
CA072720, P50 CA105009, P50 CA136393, R01 CA-1491429, R01 CA049449, R01
CA050385, R01 CA054419, R01 CA058598, R01 CA058860, R01 CA063678, R01
CA063682, R01 CA067262, R01 CA074850, R01 CA076016, R01 CA080742, R01
CA083918, R01 CA087538, R01 CA087696, R01 CA112523, R01 CA114343, R01
CA122443, R01 CA126841, R01 CA136924, R01 CA149429, R01-CA076016, R03
CA113148, R03 CA115195, R25 CA147832, R25T CA147832, U01 CA049449, U01
CA058860, U01 CA067262, U01 CA069417, U19 CA148112]; NIEHS NIH HHS [T32
ES013678, T32ES013678]
NR 36
TC 2
Z9 2
U1 1
U2 8
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0741-0395
EI 1098-2272
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD DEC
PY 2015
VL 39
IS 8
BP 689
EP 697
DI 10.1002/gepi.21921
PG 9
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA CY7RA
UT WOS:000366605200009
PM 26399219
ER
PT J
AU Mastwal, S
Ye, YZ
Ren, M
Jimenez, D
Martinowich, K
Gerfen, CR
Wang, KH
AF Mastwal, Surjeet
Ye, Yizhou
Ren, Ming
Jimenez, Dennisse
Martinowich, Keri
Gerfen, Charles R.
Wang, Kuan Hong
TI Phasic dopamine neuron activity elicits unique mesofrontal plasticity in
adolescence
SO INTERNATIONAL JOURNAL OF DEVELOPMENTAL NEUROSCIENCE
LA English
DT Meeting Abstract
CT Joint Meeting of the 20th Biennial Meeting of the
International-Society-for-Developmental-Neuroscience / 5th Annual
NeuroDevNet Brain Development Conference
CY JUL 19-24, 2014
CL Montreal, CANADA
SP Int Soc Dev Neuroscience
C1 [Mastwal, Surjeet; Ye, Yizhou; Ren, Ming; Wang, Kuan Hong] NIMH, Unit Neural Circuits & Adapt Behav, Genes Cognit & Psychosis Program, NIH, Bethesda, MD 20892 USA.
[Jimenez, Dennisse; Martinowich, Keri] Johns Hopkins Univ, Sch Med, Lieber Inst Brain Dev, Baltimore, MD 21205 USA.
[Martinowich, Keri] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA.
[Martinowich, Keri] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA.
[Gerfen, Charles R.] NIMH, Lab Syst Neurosci, NIH, Bethesda, MD 20892 USA.
EM wkuan@mail.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 0
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0736-5748
EI 1873-474X
J9 INT J DEV NEUROSCI
JI Int. J. Dev. Neurosci.
PD DEC
PY 2015
VL 47
SI SI
BP 95
EP 95
DI 10.1016/j.ijdevneu.2015.04.259
PN A
PG 1
WC Developmental Biology; Neurosciences
SC Developmental Biology; Neurosciences & Neurology
GA CY6QT
UT WOS:000366534600249
PM 26531581
ER
PT J
AU Wu, DY
AF Wu, Da-Yu
TI New research priorities of the National Institute on Drug Abuse (NIDA):
Cannabis effects on brain development
SO INTERNATIONAL JOURNAL OF DEVELOPMENTAL NEUROSCIENCE
LA English
DT Meeting Abstract
CT Joint Meeting of the 20th Biennial Meeting of the
International-Society-for-Developmental-Neuroscience / 5th Annual
NeuroDevNet Brain Development Conference
CY JUL 19-24, 2014
CL Montreal, CANADA
SP Int Soc Dev Neuroscience
C1 [Wu, Da-Yu] NIDA, Div Basic Neurosci & Behav Res, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 1
U2 7
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0736-5748
EI 1873-474X
J9 INT J DEV NEUROSCI
JI Int. J. Dev. Neurosci.
PD DEC
PY 2015
VL 47
SI SI
BP 96
EP 96
DI 10.1016/j.ijdevneu.2015.04.263
PN A
PG 1
WC Developmental Biology; Neurosciences
SC Developmental Biology; Neurosciences & Neurology
GA CY6QT
UT WOS:000366534600253
PM 26531585
ER
PT J
AU Kim, C
Prasad, V
AF Kim, Chul
Prasad, Vinay
TI Cancer Drugs Approved on the Basis of a Surrogate End Point and
Subsequent Overall Survival: An Analysis of 5 Years of US Food and Drug
Administration Approvals
SO JAMA INTERNAL MEDICINE
LA English
DT Letter
C1 [Kim, Chul] NCI, Med Oncol Serv, NIH, Bethesda, MD 20892 USA.
[Prasad, Vinay] Oregon Hlth & Sci Univ, Knight Canc Ctr, Div Hematol & Med Oncol, Portland, OR 97239 USA.
RP Prasad, V (reprint author), Oregon Hlth & Sci Univ, Knight Canc Ctr, Div Hematol & Med Oncol, 3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA.
EM prasad@ohsu.edu
NR 4
TC 24
Z9 25
U1 1
U2 3
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 2168-6106
EI 2168-6114
J9 JAMA INTERN MED
JI JAMA Intern. Med.
PD DEC
PY 2015
VL 175
IS 12
BP 1992
EP 1994
DI 10.1001/jamainternmed.2015.5868
PG 4
WC Medicine, General & Internal
SC General & Internal Medicine
GA CY3TE
UT WOS:000366332000031
PM 26502403
ER
PT J
AU Teach, SJ
Gill, MA
Togias, A
Sorkness, CA
Arbes, SJ
Calatroni, A
Wildfire, JJ
Gergen, PJ
Cohen, RT
Pongracic, JA
Kercsmar, CM
Hershey, GKK
Gruchalla, RS
Liu, AH
Zoratti, EM
Kattan, M
Grindle, KA
Gern, JE
Busse, WW
Szefler, SJ
AF Teach, Stephen J.
Gill, Michelle A.
Togias, Alkis
Sorkness, Christine A.
Arbes, Samuel J., Jr.
Calatroni, Agustin
Wildfire, Jeremy J.
Gergen, Peter J.
Cohen, Robyn T.
Pongracic, Jacqueline A.
Kercsmar, Carolyn M.
Hershey, Gurjit K. Khurana
Gruchalla, Rebecca S.
Liu, Andrew H.
Zoratti, Edward M.
Kattan, Meyer
Grindle, Kristine A.
Gern, James E.
Busse, William W.
Szefler, Stanley J.
TI Preseasonal treatment with either omalizumab or an inhaled
corticosteroid boost to prevent fall asthma exacerbations
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Article
DE Asthma; fall season; omalizumab; inhaled corticosteroid; asthma
exacerbations; rhinovirus; IFN-alpha
ID INNER-CITY CHILDREN; ALLERGIC-ASTHMA; EOSINOPHILIC ASTHMA;
IMMUNE-RESPONSES; RANDOMIZED-TRIAL; RISK-FACTORS; RHINOVIRUS; IGE;
MEPOLIZUMAB; ADOLESCENTS
AB Background: Short-term targeted treatment can potentially prevent fall asthma exacerbations while limiting therapy exposure. Objective: We sought to compare (1) omalizumab with placebo and (2) omalizumab with an inhaled corticosteroid (ICS) boost with regard to fall exacerbation rates when initiated 4 to 6 weeks before return to school.
Methods: A 3-arm, randomized, double-blind, double placebo-controlled, multicenter clinical trial was conducted among inner-city asthmatic children aged 6 to 17 years with 1 or more recent exacerbations (clincaltrials.gov #NCT01430403). Guidelines-based therapy was continued over a 4- to 9-month run-in phase and a 4-month intervention phase. In a subset the effects of omalizumab on IFN-alpha responses to rhinovirus in PBMCs were examined.
Results: Before the falls of 2012 and 2013, 727 children were enrolled, 513 were randomized, and 478 were analyzed. The fall exacerbation rate was significantly lower in the omalizumab versus placebo arms (11.3% vs 21.0%; odds ratio [OR], 0.48; 95% CI, 0.25-0.92), but there was no significant difference between omalizumab and ICS boost (8.4% vs 11.1%; OR, 0.73; 95% CI, 0.33-1.64). In a prespecified subgroup analysis, among participants with an exacerbation during the run-in phase, omalizumab was significantly more efficacious than both placebo (6.4% vs 36.3%; OR, 0.12; 95% CI, 0.02-0.64) and ICS boost (2.0% vs 27.8%; OR, 0.05; 95% CI, 0.002-0.98). Omalizumab improved IFN-a responses to rhinovirus, and within the omalizumab group, greater IFN-a increases were associated with fewer exacerbations (OR, 0.14; 95% CI, 0.01-0.88). Adverse events were rare and similar among arms.
Conclusions: Adding omalizumab before return to school to ongoing guidelines-based care among inner-city youth reduces fall asthma exacerbations, particularly among those with a recent exacerbation.
C1 [Teach, Stephen J.] Childrens Natl Hlth Syst, Div Emergency Med, Washington, DC 20010 USA.
[Teach, Stephen J.] Childrens Natl Hlth Syst, Dept Pediat, Washington, DC 20010 USA.
[Gill, Michelle A.; Gruchalla, Rebecca S.] Univ Texas SW Med Ctr Dallas, Dept Pediat, Dallas, TX 75390 USA.
[Gill, Michelle A.] Univ Texas SW Med Ctr Dallas, Dept Immunol, Dallas, TX 75390 USA.
[Togias, Alkis; Gergen, Peter J.] NIAID, Bethesda, MD 20892 USA.
[Sorkness, Christine A.; Grindle, Kristine A.; Gern, James E.; Busse, William W.] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI USA.
[Arbes, Samuel J., Jr.; Calatroni, Agustin; Wildfire, Jeremy J.] Rho Inc, Fed Syst Div, Chapel Hill, NC USA.
[Cohen, Robyn T.] Boston Univ, Sch Med, Boston, MA 02215 USA.
[Pongracic, Jacqueline A.] Ann & Robert H Lurie Childrens Hosp Chicago, Chicago, IL 60611 USA.
[Kercsmar, Carolyn M.; Hershey, Gurjit K. Khurana] Cincinnati Childrens Hosp, Denver, CO USA.
[Liu, Andrew H.] Natl Jewish Hlth, Denver, CO USA.
[Zoratti, Edward M.] Henry Ford Hosp, Dept Internal Med, Div Allergy & Immunol, Detroit, MI 48202 USA.
[Kattan, Meyer] Columbia Univ, Coll Phys & Surg, New York, NY USA.
[Liu, Andrew H.; Szefler, Stanley J.] Childrens Hosp Colorado, Aurora, CO USA.
[Liu, Andrew H.; Szefler, Stanley J.] Univ Colorado, Sch Med, Aurora, CO USA.
RP Teach, SJ (reprint author), Childrens Natl Hlth Syst, 111 Michigan Ave NW, Washington, DC 20010 USA.
EM steach@childrensnational.org
OI Togias, Alkis/0000-0001-9009-5717; Khurana Hershey,
Gurjit/0000-0001-6663-977X; Cohen, Robyn/0000-0002-6902-3118
FU National Institute of Allergy and Infectious Diseases, National
Institutes of Health, Department of Health and Human Services
[HHSN272200900052C, HHSN272201000052I]; National Center for Research
Resources; National Center for Advancing Translational Sciences,
National Institutes of Health [NCRR/NIH UL1TR000451, 1UL1RR025780,
UL1TR000075, NCATS/NIH UL1 TR000154, UL1 TR000077-04, NCATS/NIH
UL1TR000040, UL1TR000150, UL1TR001105, NIH NIAID 5R01AI098077,
UM1AI109565]
FX This project has been funded in whole or in part with federal funds from
the National Institute of Allergy and Infectious Diseases, National
Institutes of Health, Department of Health and Human Services, under
contracts HHSN272200900052C and HHSN272201000052I. Additional support
was provided by the National Center for Research Resources and the
National Center for Advancing Translational Sciences, National
Institutes of Health, under grants NCRR/NIH UL1TR000451, 1UL1RR025780,
UL1TR000075 and NCATS/NIH UL1 TR000154, UL1 TR000077-04, NCATS/NIH
UL1TR000040, UL1TR000150, and UL1TR001105, NIH NIAID 5R01AI098077, and
UM1AI109565. The following were donated: omalizumab and matching placebo
by Novartis and fluticasone and matching placebo by GlaxoSmithKline
under a clinical trial agreement with the University of
Wisconsin-Madison; EpiPens by Mylan; and Ayr nasal rinse by B.F. Ascher
& Company.
NR 31
TC 34
Z9 36
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 DEC
PY 2015
VL 136
IS 6
BP 1476
EP 1485
DI 10.1016/j.jaci.2015.09.008
PG 10
WC Allergy; Immunology
SC Allergy; Immunology
GA CX9RZ
UT WOS:000366044300006
PM 26518090
ER
PT J
AU Carter, MC
Clayton, ST
Komarow, HD
Brittain, EH
Scott, LM
Cantave, D
Gaskins, DM
Maric, I
Metcalfe, DD
AF Carter, Melody C.
Clayton, Sarah T.
Komarow, Hirsh D.
Brittain, Erica H.
Scott, Linda M.
Cantave, Daly
Gaskins, Donna M.
Maric, Irina
Metcalfe, Dean D.
TI Assessment of clinical findings, tryptase levels, and bone marrow
histopathology in the management of pediatric mastocytosis
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Article
DE Mast cells; tryptase; urticaria pigmentosa; cutaneous mastocytosis;
diffuse cutaneous mastocytosis; mastocytosis; bone marrow examination
ID CUTANEOUS MASTOCYTOSIS; SYSTEMIC MASTOCYTOSIS; URTICARIA-PIGMENTOSA;
FOLLOW-UP; CHILDREN; ADULTS; ONSET; RECOMMENDATIONS; INVOLVEMENT;
DIAGNOSIS
AB Background: The management of children with pediatric mastocytosis poses a challenge. This is because there is limited information as to the application of clinical and laboratory findings and bone marrow histopathology as they relate to medical intervention and communication.
Objective: We sought to examine clinical aspects of pediatric mastocytosis in relationship to serum tryptase levels and bone marrow pathology to provide practical guidance for management.
Methods: Between 1986 and 2012, 105 children were evaluated at the National Institutes of Health. Organomegaly was confirmed by means of ultrasound. Baseline tryptase levels and at least 1 subsequent tryptase measurement was available in 84 and 37 of these children, respectively. Fifty-three children underwent a bone marrow examination. These data were used to examine relationships between clinical findings, tryptase levels, and marrow histopathology.
Results: In patients with high tryptase levels and severe mediator symptoms, all with organomegaly had systemic disease, and none without organomegaly had systemic disease. Serum tryptase levels differed significantly between patients with urticaria pigmentosa and those with diffuse cutaneous (P < .0001) and systemic mastocytosis (P < .0001) and in all 3 categories versus control subjects (P < .0001). Tryptase levels and symptoms decreased over time in most patients, and tryptase levels correlated with bone marrow mast cell burden in patients with systemic mastocytosis (P < .0001). There was a significant relationship between clinical resolution and the percentage decrease in tryptase levels (P = .0014).
Conclusions: The majority of children experienced major or complete disease resolution (57%), whereas the remainder exhibited partial improvement. Organomegaly was a strong indicator of systemic disease. Serum tryptase levels furthered classification and reflected clinicopathologic findings, while sequential tryptase measurements were useful in supplementing clinical judgment as to disease course.
C1 [Carter, Melody C.; Clayton, Sarah T.; Komarow, Hirsh D.; Scott, Linda M.; Gaskins, Donna M.; Metcalfe, Dean D.] NIAID, Lab Allerg Dis, Bethesda, MD 20892 USA.
[Brittain, Erica H.] NIAID, Biostat Res Branch, Bethesda, MD 20892 USA.
[Cantave, Daly] NIH, Dept Nursing, Clin Ctr, Bethesda, MD 20892 USA.
[Maric, Irina] NIH, Hematol Sect, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA.
RP Carter, MC (reprint author), Bldg 10-11C207,10 Ctr Dr,MSC 1881, Bethesda, MD 20892 USA.
EM mcarter@niaid.nih.gov
FU Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, National Institutes of Health
FX Supported by the Division of Intramural Research, National Institute of
Allergy and Infectious Diseases, National Institutes of Health.
NR 25
TC 3
Z9 3
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 DEC
PY 2015
VL 136
IS 6
BP 1673
EP U378
DI 10.1016/j.jaci.2015.04.024
PG 10
WC Allergy; Immunology
SC Allergy; Immunology
GA CX9RZ
UT WOS:000366044300030
PM 26044856
ER
PT J
AU Bernhardt, ML
Zhang, YP
Erxleben, CF
Padilla-Banks, E
McDonough, CE
Miao, YL
Armstrong, DL
Williams, CJ
AF Bernhardt, Miranda L.
Zhang, Yingpei
Erxleben, Christian F.
Padilla-Banks, Elizabeth
McDonough, Caitlin E.
Miao, Yi-Liang
Armstrong, David L.
Williams, Carmen J.
TI Ca(V)3.2 T-type channels mediate Ca2+ entry during oocyte maturation and
following fertilization
SO JOURNAL OF CELL SCIENCE
LA English
DT Article
DE Oocyte; Ca2+; T-type channel; Meiosis; Fertilization; Egg activation
ID MOUSE EGG ACTIVATION; REPETITIVE CALCIUM TRANSIENTS; MEIOTIC MATURATION;
EMBRYO DEVELOPMENT; HYPERPOLARIZING RESPONSES; INTRACELLULAR CALCIUM;
ENDOPLASMIC-RETICULUM; SPERMATOGENIC CELLS; COMPARATIVE BIOLOGY;
POLYSPERMY BLOCK
AB Initiation of mouse embryonic development depends upon a series of fertilization-induced rises in intracellular Ca2+. Complete egg activation requires influx of extracellular Ca2+; however, the channels that mediate this influx remain unknown. Here, we tested whether the alpha 1 subunit of the T-type channel Ca(V)3.2, encoded by Cacna1h, mediates Ca2+ entry into oocytes. We show that mouse eggs express a robust voltage-activated Ca2+ current that is completely absent in Cacna1h(-/-) eggs. Cacna1h(-/-) females have reduced litter sizes, and careful analysis of Ca2+ oscillation patterns in Cacna1h(-/-) eggs following in vitro fertilization (IVF) revealed reductions in first transient length and oscillation persistence. Total and endoplasmic reticulum (ER) Ca2+ stores were also reduced in Cacna1h(-/-) eggs. Pharmacological inhibition of Ca(V)3.2 in wild-type CF-1 strain eggs using mibefradil or pimozide reduced Ca2+ store accumulation during oocyte maturation and reduced Ca2+ oscillation persistence, frequency and number following IVF. Overall, these data show that Ca(V)3.2 T-type channels have prev8iously unrecognized roles in supporting the meiotic-maturation-associated increase in ER Ca2+ stores and mediating Ca2+ influx required for the activation of development.
C1 [Bernhardt, Miranda L.; Zhang, Yingpei; Padilla-Banks, Elizabeth; McDonough, Caitlin E.; Williams, Carmen J.] NIH, Reprod & Dev Biol Lab, Res Triangle Pk, NC 27709 USA.
[Erxleben, Christian F.; Armstrong, David L.] NIH, Neurobiol Lab, Res Triangle Pk, NC 27709 USA.
[Miao, Yi-Liang] Huazhong Agr Univ, Coll Anim Sci & Technol, Key Lab Anim Genet Breeding & Reprod, Minist Educ, Wuhan 430070, Peoples R China.
RP Williams, CJ (reprint author), NIH, Reprod & Dev Biol Lab, Res Triangle Pk, NC 27709 USA.
EM williamsc5@niehs.nih.gov
FU Intramural Research Program of the National Institutes of Health,
National Institutes of Environmental Health Sciences [1ZIAES102985]
FX This work was supported by the Intramural Research Program of the
National Institutes of Health, National Institutes of Environmental
Health Sciences [grant number 1ZIAES102985]. Deposited in PMC for
release after 12 months.
NR 67
TC 5
Z9 5
U1 3
U2 9
PU COMPANY OF BIOLOGISTS LTD
PI CAMBRIDGE
PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL,
CAMBS, ENGLAND
SN 0021-9533
EI 1477-9137
J9 J CELL SCI
JI J. Cell Sci.
PD DEC 1
PY 2015
VL 128
IS 23
BP 4442
EP 4452
DI 10.1242/jcs.180026
PG 11
WC Cell Biology
SC Cell Biology
GA CY3NL
UT WOS:000366316400020
PM 26483387
ER
PT J
AU Gold, AL
Jarcho, JM
Rosen, DK
Pine, DS
Ernst, M
AF Gold, Andrea L.
Jarcho, Johanna M.
Rosen, Dana K.
Pine, Daniel S.
Ernst, Monique
TI Emotional and Nonemotional Conflict Processing in Pediatric and Adult
Anxiety Disorders
SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY
LA English
DT Article
ID ERROR-RELATED NEGATIVITY; OBSESSIVE-COMPULSIVE DISORDER; GENERALIZED
ANXIETY; COGNITIVE CONTROL; BRAIN ACTIVITY; TRAIT ANXIETY;
BEHAVIORAL-INHIBITION; DEPRESSIVE-DISORDERS; IMPLICIT REGULATION;
ADAPTATION
AB Objective: Perturbations in emotional conflict adaptation, an implicit regulatory process, have been observed in adult anxiety disorders. However, findings remain inconsistent and restricted to adults. The current study compares conflict adaptation in youth and adults, with and without anxiety disorders. We predicted conflict adaptation would be present in the healthy but not the anxious groups. Methods: In a clinic setting, 111 participants (27 healthy youth, 22 anxious youth, 41 healthy adults, and 21 anxious adults) completed emotional and nonemotional conflict tasks. Groups did not differ (all p's >0.1) on intelligence quotient (IQ), gender, and socioeconomic status; age did not differ between healthy and anxious subjects in either age cohort. Separate four way mixed-design analyses of variance were conducted to test hypotheses regarding the influence of diagnosis, age group, and task type on accuracy (percent correct) and reaction time (RT) for conflict adaptation (incongruent trials preceded by incongruent vs. congruent trials) and conflict detection (incongruent vs. congruent trials). Results: Measures of conflict adaptation did not interact with diagnosis or age. There was a significant main effect of conflict adaptation across the overall sample in the expected direction for accuracy, but not RT. The well-replicated conflict detection effect also did emerge across tasks, with slower RT and lower accuracy for incongruent than for congruent trials. These effects were greater for the emotional than for nonemotional tasks. Finally, there were age differences in accuracy-based conflict detection specific to the emotional task, for which the size of the effect was larger for youth than for adults. Conclusions: The current study of youth and adults did not replicate prior behavioral findings of failure to engage conflict adaptation in anxiety disorders. Therefore, more work is needed before widely adopting conflict adaptation paradigms as a standard neurocognitive marker for anxiety disorders.
C1 [Gold, Andrea L.; Jarcho, Johanna M.; Rosen, Dana K.; Pine, Daniel S.; Ernst, Monique] NIMH, Sect Dev & Affect Neurosci, NIH, Bethesda, MD 20892 USA.
RP Gold, AL (reprint author), NIH, 9000 Rockville Pike MSC 2670,Bldg 15K, Bethesda, MD 20892 USA.
EM andrea.gold@nih.gov
OI Jarcho, Johanna/0000-0001-9075-6968; Gold, Andrea/0000-0003-4447-776X
FU Intramural NIH HHS
NR 50
TC 0
Z9 0
U1 3
U2 8
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 DEC 1
PY 2015
VL 25
IS 10
BP 754
EP 763
DI 10.1089/cap.2015.0066
PG 10
WC Pediatrics; Pharmacology & Pharmacy; Psychiatry
SC Pediatrics; Pharmacology & Pharmacy; Psychiatry
GA CY9JT
UT WOS:000366723900004
PM 26544668
ER
PT J
AU Matsudaira, T
Gow, RV
Kelly, J
Murphy, C
Potts, L
Sumich, A
Ghebremeskel, K
Crawford, MA
Taylor, E
AF Matsudaira, Toshiko
Gow, Rachel V.
Kelly, Joanna
Murphy, Caroline
Potts, Laura
Sumich, Alexander
Ghebremeskel, Kebreab
Crawford, Michael A.
Taylor, Eric
TI Biochemical and Psychological Effects of Omega-3/6 Supplements in Male
Adolescents with Attention-Deficit/Hyperactivity Disorder: A Randomized,
Placebo-Controlled, Clinical Trial
SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY
LA English
DT Article
ID DEFICIT HYPERACTIVITY DISORDER; POLYUNSATURATED FATTY-ACIDS; BRAIN
DOCOSAHEXAENOIC ACID; YOUNG-ADULT PRISONERS; DOUBLE-BLIND; LINOLENIC
ACID; CHILDREN; BEHAVIOR; ADHD; RATS
AB Background: An abnormality in long chain-polyunsaturated fatty acid (LC-PUFA) levels has been implicated in attention-deficit/hyperactivity disorder (ADHD). Studies evaluating LC-PUFA supplementation for therapeutic efficacy in ADHD have shown mixed and, therefore, inconclusive results. Methods: Seventy-six male adolescents (age 12-16 years, mean=13.7) with ADHD were assessed for the effects of 12 weeks omega-3 and omega-6 supplements on biochemical and psychological outcomes in a randomized, placebo-controlled, clinical trial. The primary outcome measure was change in the Conners' Teacher Rating Scales (CTRS) following 12 weeks of supplementation of LC-PUFA or placebo. At baseline, the placebo and treatment groups had comparable levels of LC-PUFA as measured by red blood cell phosphatidylcholine. In the treatment group, supplementation enhanced eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and total omega-3 fatty acid levels. Results: No superiority of LC-PUFAs to placebo was observed on the primary outcome. Further, there were no reliable treatment effects on aggression, impulsivity, depression, and anxiety. Conclusions: Future studies should use larger sample sizes and longer supplementation period to detect small-modest effects for clinical recommendations in ADHD.
C1 [Matsudaira, Toshiko; Taylor, Eric] Inst Psychiat Psychol & Neurosci, Dept Adolescent & Child Psychiat, London, England.
[Gow, Rachel V.] NIH, Sect Nutr Neurosci, Bethesda, MD 20892 USA.
[Kelly, Joanna; Murphy, Caroline; Potts, Laura] Inst Psychiat, Dept Biostat, Kings Clin Trials Unit, London, England.
[Sumich, Alexander] Nottingham Trent Univ, Sch Social Sci, Div Psychol, Nottingham, England.
[Ghebremeskel, Kebreab] London Metropolitan Univ, Lipid & Nutr Res Ctr, London, England.
[Crawford, Michael A.] Univ London Imperial Coll Sci Technol & Med, Fac Med, Reprod Physiol, London, England.
RP Matsudaira, T (reprint author), 1-15-9 Sekiguchi,Bunkyo Ku, Tokyo 1120014, Japan.
EM toshimatsudaira@yahoo.co.jp
NR 58
TC 2
Z9 2
U1 6
U2 20
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 DEC 1
PY 2015
VL 25
IS 10
BP 775
EP 782
DI 10.1089/cap.2015.0052
PG 8
WC Pediatrics; Pharmacology & Pharmacy; Psychiatry
SC Pediatrics; Pharmacology & Pharmacy; Psychiatry
GA CY9JT
UT WOS:000366723900006
PM 26682998
ER
PT J
AU Calkins, ME
Merikangas, KR
Moore, TM
Burstein, M
Behr, MA
Satterthwaite, TD
Ruparel, K
Wolf, DH
Roalf, DR
Mentch, FD
Qiu, HJ
Chiavacci, R
Connolly, JJ
Sleiman, PMA
Gur, RC
Hakonarson, H
Gur, RE
AF Calkins, Monica E.
Merikangas, Kathleen R.
Moore, Tyler M.
Burstein, Marcy
Behr, Meckenzie A.
Satterthwaite, Theodore D.
Ruparel, Kosha
Wolf, Daniel H.
Roalf, David R.
Mentch, Frank D.
Qiu, Haijun
Chiavacci, Rosetta
Connolly, John J.
Sleiman, Patrick M. A.
Gur, Ruben C.
Hakonarson, Hakon
Gur, Raquel E.
TI The Philadelphia Neurodevelopmental Cohort: constructing a deep
phenotyping collaborative
SO JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY
LA English
DT Article
DE Community cohort; children; adolescents; young adults; psychopathology;
mood; anxiety; behavior; psychosis; comorbidity; structure; genomics;
neuroimaging; neurocognition; public domain
ID SUPPLEMENT NCS-A; COMMON MENTAL-DISORDERS; COMMUNITY SAMPLE; PSYCHOSIS
SPECTRUM; SEX-DIFFERENCES; SUBSTANCE USE; RISK-FACTORS; FIT INDEXES;
REPLICATION; COMORBIDITY
AB Background: An integrative multidisciplinary approach is required to elucidate the multiple factors that shape neurodevelopmental trajectories of mental disorders. The Philadelphia Neurodevelopmental Cohort (PNC), funded by the National Institute of Mental Health Grand Opportunity (GO) mechanism of the American Recovery and Reinvestment Act, was designed to characterize clinical and neurobehavioral phenotypes of genotyped youths. Data generated, which are recently available through the NIMH Database of Genotypes and Phenotypes (dbGaP), have garnered considerable interest. We provide an overview of PNC recruitment and clinical assessment methods to allow informed use and interpretation of the PNC resource by the scientific community. We also evaluate the structure of the assessment tools and their criterion validity. Methods: Participants were recruited from a large pool of youths (n = 13,958) previously identified and genotyped at The Children's Hospital of Philadelphia. A comprehensive computerized tool for structured evaluation of psychopathology domains (GOASSESS) was constructed. We administered GOASSESS to all participants and used factor analysis to evaluate its structure. Results: A total of 9,498 youths (aged 8-21; mean age = 14.2; European American = 55.8%; African American = 32.9%; Other = 11.4%) were enrolled. Factor analysis revealed a strong general psychopathology factor, and specific 'anxious-misery', 'fear', and 'behavior' factors. The 'behavior' factor had a small negative correlation (-0.21) with overall accuracy of neurocognitive performance, particularly in tests of executive and complex reasoning. Being female had a high association with the 'anxious-misery' and low association with the 'behavior' factors. The psychosis spectrum was also best characterized by a general factor and three specific factors: ideas about 'special abilities/persecution,' 'unusual thoughts/perceptions', and 'negative/disorganized' symptoms. Conclusions: The PNC assessment mechanism yielded psychopathology data with strong factorial validity in a large diverse community cohort of genotyped youths. Factor scores should be useful for dimensional integration with other modalities (neuroimaging, genomics). Thus, PNC public domain resources can advance understanding of complex interrelationships among genes, cognition, brain, and behavior involved in neurodevelopment of common mental disorders.
C1 [Calkins, Monica E.; Moore, Tyler M.; Satterthwaite, Theodore D.; Ruparel, Kosha; Wolf, Daniel H.; Roalf, David R.; Gur, Ruben C.; Gur, Raquel E.] Univ Penn, Dept Psychiat, Neuropsychiat Sect, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Merikangas, Kathleen R.; Burstein, Marcy] NIMH, Genet Epidemiol Res Branch, Intramural Res Program, Bethesda, MD 20892 USA.
[Behr, Meckenzie A.; Mentch, Frank D.; Qiu, Haijun; Chiavacci, Rosetta; Connolly, John J.; Hakonarson, Hakon] Childrens Hosp Philadelphia, Ctr Appl Genom, Philadelphia, PA 19104 USA.
[Sleiman, Patrick M. A.] Univ Penn, Dept Pediat, Perelman Sch Med, Philadelphia, PA 19104 USA.
RP Calkins, ME (reprint author), Univ Penn, Dept Psychiat, Neuropsychiat Sect, Perelman Sch Med, 9 Maloney,3600 Spruce St, Philadelphia, PA 19104 USA.
EM mcalkins@upenn.edu
FU National Institute of Mental Health [MH089983, MH089924, K08MH079364,
K23MH098130]; Dowshen Program for Neuroscience; Marc Rapport Family
Investigator grant through Brain and Behavior Foundation
FX This work was supported by the National Institute of Mental Health
(R.E.G. and H.H, RC2 grant numbers MH089983 and MH089924), (M.E.C.,
grant number K08MH079364), and (T.D.S., grant number K23MH098130); the
Dowshen Program for Neuroscience; and the Marc Rapport Family
Investigator grant through the Brain and Behavior Foundation (T.D.S.).
The authors thank the participants of this study, and all the members of
the Recruitment, Assessment, and Data Teams whose individual
contributions collectively made this work possible. Also William G.
Iacono and Genevieve Ryczek (University of Minnesota Center for Twin and
Family Research; MCTFR) for their consultation while developing our
recruitment strategy, and Iacono for allowing use, modification, and
computerization of the MCFTR substance use measure. The authors have
declared that they have no competing or potential conflicts of interest.
NR 43
TC 10
Z9 10
U1 3
U2 8
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0021-9630
EI 1469-7610
J9 J CHILD PSYCHOL PSYC
JI J. Child Psychol. Psychiatry
PD DEC
PY 2015
VL 56
IS 12
BP 1356
EP 1369
DI 10.1111/jcpp.12416
PG 14
WC Psychology, Developmental; Psychiatry; Psychology
SC Psychology; Psychiatry
GA CY6IK
UT WOS:000366512300010
PM 25858255
ER
PT J
AU Lee, C
Kim, KP
Bolch, WE
Moroz, BE
Folio, L
AF Lee, Choonsik
Kim, Kwang Pyo
Bolch, Wesley E.
Moroz, Brian E.
Folio, Les
TI NCICT: a computational solution to estimate organ doses for pediatric
and adult patients undergoing CT scans
SO JOURNAL OF RADIOLOGICAL PROTECTION
LA English
DT Article
DE computed tomography; organ dose; computational phantoms; Monte Carlo
simulation
ID COMPUTED-TOMOGRAPHY; RADIATION-EXPOSURE; HYBRID PHANTOMS; HUMAN ANATOMY;
BRAIN-TUMORS; DOSIMETRY; MODELS; PROTECTION; LEUKEMIA; PROGRAM
AB We developed computational methods and tools to assess organ doses for pediatric and adult patients undergoing computed tomography (CT) examinations. We used the International Commission on Radiological Protection (ICRP) reference pediatric and adult phantoms combined with the Monte Carlo simulation of a reference CT scanner to establish comprehensive organ dose coefficients (DC), organ absorbed dose per unit volumetric CT Dose Index (CTDIvol) (mGy/mGy). We also developed methods to estimate organ doses with tube current modulation techniques and size specific dose estimates. A graphical user interface was designed to obtain user input of patient- and scan-specific parameters, and to calculate and display organ doses. A batch calculation routine was also integrated into the program to automatically calculate organ doses for a large number of patients. We entitled the computer program, National Cancer Institute dosimetry system for CT(NCICT). We compared our dose coefficients with those from CT-Expo, and evaluated the performance of our program using CT patient data. Our pediatric DCs show good agreements of organ dose estimation with those from CT-Expo except for thyroid. Our results support that the adult phantom in CT-Expo seems to represent a pediatric individual between 10 and 15 years rather than an adult. The comparison of CTDIvol values between NCICT and dose pages from 10 selected CT scans shows good agreements less than 12% except for two cases (up to 20%). The organ dose comparison between mean and modulated mAs shows that mean mAs-based calculation significantly overestimates dose (up to 2.4-fold) to the organs in close proximity to lungs in chest and chest-abdomen-pelvis scans. Our program provides more realistic anatomy based on the ICRP reference phantoms, higher age resolution, the most up-to-date bone marrow dosimetry, and several convenient features compared to previous tools. The NCICT will be available for research purpose in the near future.
C1 [Lee, Choonsik; Moroz, Brian E.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Kim, Kwang Pyo] Kyung Hee Univ, Dept Nucl Engn, Gyeonggi Do, South Korea.
[Bolch, Wesley E.] Univ Florida, Dept Biomed Engn, Gainesville, FL 32611 USA.
[Folio, Les] NIH, Radiol & Imaging Sci Clin Ctr, Bethesda, MD 20892 USA.
RP Lee, C (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20850 USA.
EM leechoonsik@mail.nih.gov
FU intramural research program of the National Institutes of Health,
National Cancer Institute, Division of Cancer Epidemiology and Genetics
FX This work was supported by the intramural research program of the
National Institutes of Health, National Cancer Institute, Division of
Cancer Epidemiology and Genetics. This study utilised the
high-performance computational capabilities of the Biowulf computing
system at the National Institutes of Health, Bethesda, MD.
(http://biowulf.nih.gov).
NR 42
TC 3
Z9 3
U1 2
U2 8
PU IOP PUBLISHING LTD
PI BRISTOL
PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND
SN 0952-4746
EI 1361-6498
J9 J RADIOL PROT
JI J. Radiol. Prot.
PD DEC
PY 2015
VL 35
IS 4
BP 891
EP 909
DI 10.1088/0952-4746/35/4/891
PG 19
WC Environmental Sciences; Public, Environmental & Occupational Health;
Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical
Imaging
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Nuclear Science & Technology; Radiology, Nuclear Medicine &
Medical Imaging
GA CY4OU
UT WOS:000366388500011
ER
PT J
AU Rahu, K
Rahu, M
Tekkel, M
Veidebaum, T
Hakulinen, T
Auvinen, A
Bigbee, WL
Hartshorne, MF
Inskip, PD
Boice, JD
AF Rahu, Kaja
Rahu, Mati
Tekkel, Mare
Veidebaum, Toomas
Hakulinen, Timo
Auvinen, Anssi
Bigbee, William L.
Hartshorne, Michael F.
Inskip, Peter D.
Boice, John D., Jr.
TI Chernobyl cleanup workers from Estonia: cohort description and related
epidemiological research
SO JOURNAL OF RADIOLOGICAL PROTECTION
LA English
DT Review
DE Chernobyl cleanup workers; cancer incidence; cohort; mortality;
radiation exposure; record linkage; suicide
ID MINISATELLITE MUTATION-RATE; CANCER INCIDENCE; THYROID-CANCER;
FOLLOW-UP; RISK; LIQUIDATORS; ACCIDENT; BIODOSIMETRY; MORTALITY;
CHILDREN
AB The Estonian study of Chernobyl cleanup workers was one of the first investigations to evaluate the possible health consequences of working in the Chernobyl area (the 30 km exclusion zone and/or adjacent territories) after the 1986 reactor accident. The cohort consists of 4831 men who were dispatched in 1986-1991 for tasks involving decontamination, construction of buildings, transport, radiation measurement, guard duty or other activities. By 31 December 2012, the follow-up of the cohort yielded 102 158 person-years of observation. Exposure and health data were collected by postal questionnaires, biodosimetry evaluations, thyroid screenings, and record-linkages with cancer, causes of death and health insurance reimbursement registers and databases. These data cover socio-demographic factors, employment history, aspects of health behaviour, medical history, work and living conditions in the Chernobyl area, biomarkers of exposure, cancer and non-cancer disease occurrence and causes of death. Cancer incidence data were obtained for 1986-2008, mortality data for 1986-2011 and non-cancer morbidity data for 2004-2012. Although the cohort is relatively small, it has been extensively examined and benefited from comprehensive nationwide population and health registers. The major finding was an increased risk of suicide. Thyroid examinations did not reveal an association with thyroid nodular disease and radiation dose, but did indicate the importance of accounting for screening when making comparisons with unscreened populations. No risk of leukaemia was observed and risks higher than 2.5-fold could be excluded with 95% confidence. Biodosimetry included GPA analyses and chromosomal translocation analyses and indicated that the Estonian cleanup workers experienced a relatively low mean exposure of the order of 0.1 Gy. One value of the Estonian study is in the methodologic processes brought to bear in addressing possible health effects from the Chernobyl accident. Twenty-five years of research are summarised and opportunities for the future listed.
C1 [Rahu, Kaja; Rahu, Mati; Tekkel, Mare] Natl Inst Hlth Dev, Dept Epidemiol & Biostat, Tallinn, Estonia.
[Veidebaum, Toomas] Natl Inst Hlth Dev, Tallinn, Estonia.
[Hakulinen, Timo] Finnish Canc Registry, FIN-00170 Helsinki, Finland.
[Auvinen, Anssi] Univ Tampere, Sch Hlth Sci, FIN-33101 Tampere, Finland.
[Auvinen, Anssi] STUK Radiat & Nucl Safety Author, Helsinki, Finland.
[Bigbee, William L.] Univ Pittsburgh, Sch Med, Dept Pathol, Pittsburgh, PA USA.
[Bigbee, William L.] Univ Pittsburgh, Hillman Canc Ctr, Inst Canc, Pittsburgh, PA USA.
[Hartshorne, Michael F.] Univ New Mexico, Dept Radiol, Albuquerque, NM 87131 USA.
[Inskip, Peter D.] NCI, Dept Hlth & Human Serv, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet,NIH, Bethesda, MD 20892 USA.
[Boice, John D., Jr.] Natl Council Radiat Protect & Measurements, Bethesda, MD USA.
[Boice, John D., Jr.] Vanderbilt Univ, Sch Med, Div Epidemiol, Nashville, TN 37212 USA.
RP Rahu, K (reprint author), Natl Inst Hlth Dev, Dept Epidemiol & Biostat, Tallinn, Estonia.
EM kaja.rahu@tai.ee
RI Rahu, Mati/A-9981-2008
FU Estonian Research Council [IUT5-1]; US National Cancer Institute
[N01-CP-85638-03]
FX This stage of the study was supported by the Estonian Research Council
(IUT5-1). The initial work was financed by US National Cancer Institute
Contract N01-CP-85638-03.
NR 31
TC 1
Z9 1
U1 1
U2 6
PU IOP PUBLISHING LTD
PI BRISTOL
PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND
SN 0952-4746
EI 1361-6498
J9 J RADIOL PROT
JI J. Radiol. Prot.
PD DEC
PY 2015
VL 35
IS 4
BP R35
EP R45
DI 10.1088/0952-4746/35/4/R35
PG 11
WC Environmental Sciences; Public, Environmental & Occupational Health;
Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical
Imaging
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Nuclear Science & Technology; Radiology, Nuclear Medicine &
Medical Imaging
GA CY4OU
UT WOS:000366388500003
PM 26512763
ER
PT J
AU Taylor, JK
Coleman, CM
Postel, S
Sisk, JM
Bernbaum, JG
Venkataraman, T
Sundberg, EJ
Frieman, MB
AF Taylor, Justin K.
Coleman, Christopher M.
Postel, Sandra
Sisk, Jeanne M.
Bernbaum, John G.
Venkataraman, Thiagarajan
Sundberg, Eric J.
Frieman, Matthew B.
TI Severe Acute Respiratory Syndrome Coronavirus ORF7a Inhibits Bone Marrow
Stromal Antigen 2 Virion Tethering through a Novel Mechanism of
Glycosylation Interference
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID PAPAIN-LIKE PROTEASE; SARS-CORONAVIRUS; CELL-SURFACE; MURINE
CORONAVIRUS; MOLECULAR-CLONING; AIRWAY EPITHELIA; HIV-1 RELEASE; VIRUS;
BST-2/TETHERIN; VPU
AB Severe acute respiratory syndrome (SARS) emerged in November 2002 as a case of atypical pneumonia in China, and the causative agent of SARS was identified to be a novel coronavirus, severe acute respiratory syndrome coronavirus (SARS-CoV). Bone marrow stromal antigen 2 (BST-2; also known as CD317 or tetherin) was initially identified to be a pre-B-cell growth promoter, but it also inhibits the release of virions of the retrovirus human immunodeficiency virus type 1 (HIV-1) by tethering budding virions to the host cell membrane. Further work has shown that BST-2 restricts the release of many other viruses, including the human coronavirus 229E (hCoV-229E), and the genomes of many of these viruses encode BST-2 antagonists to overcome BST-2 restriction. Given the previous studies on BST-2, we aimed to determine if BST-2 has the ability to restrict SARS-CoV and if the SARS-CoV genome encodes any proteins that modulate BST-2's antiviral function. Through an in vitro screen, we identified four potential BST-2 modulators encoded by the SARS-CoV genome: the papain-like protease (PLPro), nonstructural protein 1 (nsp1), ORF6, and ORF7a. As the function of ORF7a in SARS-CoV replication was previously unknown, we focused our study on ORF7a. We found that BST-2 does restrict SARS-CoV, but the loss of ORF7a leads to a much greater restriction, confirming the role of ORF7a as an inhibitor of BST-2. We further characterized the mechanism of BST-2 inhibition by ORF7a and found that ORF7a localization changes when BST-2 is overexpressed and ORF7a binds directly to BST-2. Finally, we also show that SARS-CoV ORF7a blocks the restriction activity of BST-2 by blocking the glycosylation of BST-2.
IMPORTANCE
The severe acute respiratory syndrome coronavirus (SARS-CoV) emerged from zoonotic sources in 2002 and caused over 8,000 infections and 800 deaths in 37 countries around the world. Identifying host factors that regulate SARS-CoV pathogenesis is critical to understanding how this lethal virus causes disease. We have found that BST-2 is capable of restricting SARS-CoV release from cells; however, we also identified a SARS-CoV protein that inhibits BST-2 function. We show that the SARS-CoV protein ORF7a inhibits BST-2 glycosylation, leading to a loss of BST-2's antiviral function.
C1 [Taylor, Justin K.; Coleman, Christopher M.; Sisk, Jeanne M.; Venkataraman, Thiagarajan; Sundberg, Eric J.; Frieman, Matthew B.] Univ Maryland, Dept Microbiol & Immunol, Baltimore, MD 21201 USA.
[Postel, Sandra; Sundberg, Eric J.] Univ Maryland, Sch Med, Inst Human Virol, Baltimore, MD 21201 USA.
[Bernbaum, John G.] NIH, Integrated Res Facil, Frederick, MD USA.
[Sundberg, Eric J.] Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA.
RP Frieman, MB (reprint author), Univ Maryland, Dept Microbiol & Immunol, Baltimore, MD 21201 USA.
EM mfrieman@som.umaryland.edu
OI Venkataraman, Thiagarajan/0000-0003-0921-6345
FU Division of Intramural Research of the National Institute of Allergy and
Infectious Diseases (NIAID) [RO1AI1095569]; NIAID [R01AI087452]
FX This work was supported by the Division of Intramural Research of the
National Institute of Allergy and Infectious Diseases (NIAID) with grant
RO1AI1095569 (to M.B.F.) and by NIAID grant R01AI087452 (to E.J.S.).
NR 54
TC 1
Z9 1
U1 1
U2 2
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 DEC
PY 2015
VL 89
IS 23
BP 11820
EP 11833
DI 10.1128/JVI.02274-15
PG 14
WC Virology
SC Virology
GA CZ1WM
UT WOS:000366896600008
PM 26378163
ER
PT J
AU Tekeste, SS
Wilkinson, TA
Weiner, EM
Xu, XW
Miller, JT
Le Grice, SFJ
Clubb, RT
Chow, SA
AF Tekeste, Shewit S.
Wilkinson, Thomas A.
Weiner, Ethan M.
Xu, Xiaowen
Miller, Jennifer T.
Le Grice, Stuart F. J.
Clubb, Robert T.
Chow, Samson A.
TI Interaction between Reverse Transcriptase and Integrase Is Required for
Reverse Transcription during HIV-1 Replication
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; DOUBLE-STRANDED DNA; TYPE-1 INTEGRASE;
RETROVIRAL INTEGRASE; NUCLEAR IMPORT; IN-VITRO; ANGSTROM RESOLUTION;
CONSERVED RESIDUES; VIRAL REPLICATION; GENETIC-ANALYSIS
AB Human immunodeficiency virus type 1 (HIV-1) replication requires reverse transcription of its RNA genome into a double-stranded cDNA copy, which is then integrated into the host cell chromosome. The essential steps of reverse transcription and integration are catalyzed by the viral enzymes reverse transcriptase (RT) and integrase (IN), respectively. In vitro, HIV-1 RT can bind with IN, and the C-terminal domain (CTD) of IN is necessary and sufficient for this binding. To better define the RT-IN interaction, we performed nuclear magnetic resonance (NMR) spectroscopy experiments to map a binding surface on the IN CTD in the presence of RT prebound to a duplex DNA construct that mimics the primer-binding site in the HIV-1 genome. To determine the biological significance of the RT-IN interaction during viral replication, we used the NMR chemical shift mapping information as a guide to introduce single amino acid substitutions of nine different residues on the putative RT-binding surface in the IN CTD. We found that six viral clones bearing such IN substitutions (R231E, W243E, G247E, A248E, V250E, and I251E) were noninfectious. Further analyses of the replication-defective IN mutants indicated that the block in replication took place specifically during early reverse transcription. The recombinant INs purified from these mutants, though retaining enzymatic activities, had diminished ability to bind RT in a cosedimentation assay. The results indicate that the RT-IN interaction is functionally relevant during the reverse transcription step of the HIV-1 life cycle.
IMPORTANCE
To establish a productive infection, human immunodeficiency virus type 1 (HIV-1) needs to reverse transcribe its RNA genome to create a double-stranded DNA copy and then integrate this viral DNA genome into the chromosome of the host cell. These two essential steps are catalyzed by the HIV-1 enzymes reverse transcriptase (RT) and integrase (IN), respectively. We have shown previously that IN physically interacts with RT, but the importance of this interaction during HIV-1 replication has not been fully characterized. In this study, we have established the biological significance of the HIV-1 RT-IN interaction during the viral life cycle by demonstrating that altering the RT-binding surface on IN disrupts both reverse transcription and viral replication. These findings contribute to our understanding of the RT-IN binding mechanism, as well as indicate that the RT-IN interaction can be exploited as a new antiviral drug target.
C1 [Tekeste, Shewit S.; Wilkinson, Thomas A.; Xu, Xiaowen; Chow, Samson A.] Univ Calif Los Angeles, Dept Mol & Med Pharmacol, Los Angeles, CA 90024 USA.
[Weiner, Ethan M.; Clubb, Robert T.] Univ Calif Los Angeles, Dept Chem & Biochem, Los Angeles, CA 90024 USA.
[Miller, Jennifer T.; Le Grice, Stuart F. J.] NCI, Basic Res Lab, Frederick, MD 21701 USA.
RP Chow, SA (reprint author), Univ Calif Los Angeles, Dept Mol & Med Pharmacol, Los Angeles, CA 90024 USA.
EM schow@mednet.ucla.edu
RI Xu, Xiaowen/C-2139-2016
FU UCLA CFAR [5P30 AI028697]; NIH [GM101416]; Science Technology Department
of Zhejiang Province, China [2012C24015]; Research Training in
Pharmacological Sciences [NIH T32GM008652]; UCLA AIDS Institute/CFAR
Fellowship Award; Intramural Research Program of the National Cancer
Institute, NIH, Department of Health and Human Services
FX The ELISA for p24 was carried out by the Center for AIDS Research (CFAR)
Virology Core Facility of the University of California, Los Angeles
(UCLA), which is supported by UCLA CFAR grant 5P30 AI028697 and the UCLA
AIDS Institute and by the UCLA Council of Bioscience Resources. This
work was partly supported by NIH grant GM101416 and an International
Collaborative grant (number 2012C24015) from the Science Technology
Department of Zhejiang Province, China, to S.A.C. S.S.T. was partly
supported by Research Training in Pharmacological Sciences (NIH
T32GM008652) and a UCLA AIDS Institute/CFAR Fellowship Award. J.T.M. and
S.F.J.L.G. are supported by the Intramural Research Program of the
National Cancer Institute, NIH, Department of Health and Human Services.
NR 79
TC 6
Z9 6
U1 3
U2 13
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 DEC
PY 2015
VL 89
IS 23
BP 12058
EP 12069
DI 10.1128/JVI.01471-15
PG 12
WC Virology
SC Virology
GA CZ1WM
UT WOS:000366896600028
PM 26401032
ER
PT J
AU Altan-Bonnet, N
Chen, YH
AF Altan-Bonnet, Nihal
Chen, Ying-Han
TI Intercellular Transmission of Viral Populations with Vesicles
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID CELLS; VIRUS; REPLICATION; RNA; ENTEROVIRUSES; PARTICLES; RELEASE;
PATHWAY; SPREAD
AB A common paradigm holds that during cell-to-cell transmission, viruses behave as lone soldiers. Recently, we discovered not only that enteroviruses are transmitted via vesicles as populations of viral particles but also that this type of transmission enhances their infection efficiency (Y. H. Chen et al., Cell 160:619-630, 2015). This mechanism could be advantageous for the overall fitness of the viral population, promoting genetic interplay by enabling viral quasispecies to collectively infect a susceptible host cell. Here, we discuss these findings in the context of viral pathogenesis and also propose that this novel type of vesicular transmission is widespread among different virus families and includes populations of both viral particles and naked viral genomes.
C1 [Altan-Bonnet, Nihal; Chen, Ying-Han] NHLBI, Lab Host Pathogen Dynam, NIH, Bethesda, MD 20892 USA.
RP Altan-Bonnet, N (reprint author), NHLBI, Lab Host Pathogen Dynam, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM nihal.altan-bonnet@nih.gov
NR 21
TC 5
Z9 5
U1 0
U2 6
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 DEC
PY 2015
VL 89
IS 24
BP 12242
EP 12244
DI 10.1128/JVI.01452-15
PG 3
WC Virology
SC Virology
GA CZ1WS
UT WOS:000366897200003
PM 26423944
ER
PT J
AU Lee, FH
Mason, R
Welles, H
Learn, GH
Keele, BF
Roederer, M
Bar, KJ
AF Lee, Fang-Hua
Mason, Rosemarie
Welles, Hugh
Learn, Gerald H.
Keele, Brandon F.
Roederer, Mario
Bar, Katharine J.
TI Breakthrough Virus Neutralization Resistance as a Correlate of
Protection in a Nonhuman Primate Heterologous Simian Immunodeficiency
Virus Vaccine Challenge Study
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID RECOMBINANT GLYCOPROTEIN-120 VACCINE; RHESUS MONOCLONAL-ANTIBODIES;
PREVENT HIV-1 INFECTION; EFFICACY TRIAL; SIEVE ANALYSIS; GP120 VACCINE;
SIV STRAIN; PHYLOGENIES; SIVSME660; RESPONSES
AB Comprehensive assessments of immune correlates of protection in human immunodeficiency virus (HIV) vaccine trials are essential to vaccine design. Neutralization sieve analysis compares the neutralization sensitivity of the breakthrough transmitted/founder (TF) viruses from vaccinated and control animals to infer the molecular mechanisms of vaccine protection. Here, we report a robust neutralization sieve effect in a nonhuman primate simian immunodeficiency virus (SIV) vaccine trial (DNA prime/recombinant adenovirus type 5 [rAd5] boost) (VRC-10-332) that demonstrated substantial protective efficacy and revealed a genetic signature of neutralization resistance in the C1 region of env. We found significant enrichment for neutralization resistance in the vaccine compared to control breakthrough TF viruses when tested with plasma from vaccinated study animals, plasma from chronically SIV-infected animals, and a panel of SIV-specific monoclonal antibodies targeting six discrete Env epitopes (P < 0.008 for all comparisons). Neutralization resistance was significantly associated with the previously identified genetic signature of resistance (P < 0.0001), and together, the results identify virus neutralization as a correlate of protection. These findings further demonstrate the in vivo relevance of our previous in vitro analyses of the SIVsmE660 challenge stock, which revealed a broad range of neutralization sensitivities of its component viruses. In sum, this report demonstrates proof-of-concept that phenotypic sieve analyses can elucidate mechanistic correlates of immune protection following vaccination and raises a cautionary note for SIV and SHIV (simian-human immunodeficiency virus) vaccine studies that employ challenge strains with envelope glycoproteins that fail to exhibit neutralization resistance profiles typical of TF viruses.
IMPORTANCE
With more than 2 million new infections annually, the development of an effective vaccine against HIV-1 is a global health priority. Understanding immunologic correlates of protection generated in vaccine trials is critical to advance vaccine development. Here, we assessed the role of vaccine-elicited neutralizing antibodies in a recent nonhuman primate study of a vaccine that showed significant protection against simian immunodeficiency virus (SIV) challenge and suggested a genetic signature of neutralization sensitivity. We found that breakthrough viruses able to establish infection in vaccinated animals were substantially more resistant to antibody-mediated neutralization than were viruses from controls. These findings suggest that vaccine-elicited neutralizing antibodies selectively blocked the transmission of more sensitive challenge viruses. Sieve analysis also corroborated a genetic signature of neutralization sensitivity and highlighted the impact of challenge swarm diversity. Our findings suggest an important role for neutralization sieve analyses as an informative component of comprehensive immune-correlates analyses.
C1 [Lee, Fang-Hua; Learn, Gerald H.; Bar, Katharine J.] Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Mason, Rosemarie; Welles, Hugh; Roederer, Mario] NIAID, Vaccine Res Ctr, Bethesda, MD 20892 USA.
[Keele, Brandon F.] Leidos Biomed Res Inc, AIDS & Canc Virus Program, Frederick Natl Lab Canc Res, Frederick, MD USA.
RP Bar, KJ (reprint author), Univ Penn, Perelman Sch Med, Philadelphia, PA 19104 USA.
EM bark@upenn.edu
OI Welles, Hugh/0000-0002-3336-1203
FU Penn Center for AIDS Research (CFAR), an NIH [P30 AI 045008]; University
of Pennsylvania; National Cancer Institute, National institutes of
Health [HHSN261200800001E]
FX This publication was made possible through statistical and sequencing
core services and support from the Penn Center for AIDS Research (CFAR),
an NIH-funded program (P30 AI 045008). We acknowledge funding from the
University of Pennsylvania and federal funds from the National Cancer
Institute, National institutes of Health, under contract no.
HHSN261200800001E.
NR 58
TC 6
Z9 6
U1 0
U2 5
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
EI 1098-5514
J9 J VIROL
JI J. Virol.
PD DEC
PY 2015
VL 89
IS 24
BP 12388
EP 12400
DI 10.1128/JVI.01531-15
PG 13
WC Virology
SC Virology
GA CZ1WS
UT WOS:000366897200016
PM 26423953
ER
PT J
AU Asokan, M
Rudicell, RS
Louder, M
McKee, K
O'Dell, S
Stewart-Jones, G
Wang, K
Xu, L
Chen, X
Choe, M
Chuang, G
Georgiev, IS
Joyce, MG
Kirys, T
Ko, S
Pegu, A
Shi, W
Todd, JP
Yang, Z
Bailer, RT
Rao, S
Kwong, PD
Nabel, GJ
Mascola, JR
AF Asokan, M.
Rudicell, R. S.
Louder, M.
McKee, K.
O'Dell, S.
Stewart-Jones, G.
Wang, K.
Xu, L.
Chen, X.
Choe, M.
Chuang, G.
Georgiev, I. S.
Joyce, M. G.
Kirys, T.
Ko, S.
Pegu, A.
Shi, W.
Todd, J. P.
Yang, Z.
Bailer, R. T.
Rao, S.
Kwong, P. D.
Nabel, G. J.
Mascola, J. R.
TI Bispecific Antibodies Targeting Different Epitopes on the HIV-1 Envelope
Exhibit Broad and Potent Neutralization
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID MONOCLONAL-ANTIBODIES; IGG ANTIBODIES; IMPROVES PROTECTION; RATIONAL
DESIGN; SHIV INFECTION; VACCINE; IMMUNIZATION; RECOGNITION; GENERATION;
MACAQUES
AB The potency and breadth of the recently isolated neutralizing human monoclonal antibodies to HIV-1 have stimulated interest in their use to prevent or to treat HIV-1 infection. Due to the antigenically diverse nature of the HIV-1 envelope (Env), no single antibody is highly active against all viral strains. While the physical combination of two broadly neutralizing antibodies (bNAbs) can improve coverage against the majority of viruses, the clinical-grade manufacturing and testing of two independent antibody products are time and resource intensive. In this study, we constructed bispecific immunoglobulins (IgGs) composed of independent antigen-binding fragments with a common Fc region. We developed four different bispecific IgG variants that included antibodies targeting four major sites of HIV-1 neutralization. We show that these bispecific IgGs display features of both antibody specificities and, in some cases, display improved coverage over the individual parental antibodies. All four bispecific IgGs neutralized 94% to 97% of antigenically diverse viruses in a panel of 206 HIV-1 strains. Among the bispecific IgGs tested, VRC07 X PG9-16 displayed the most favorable neutralization profile. It was superior in breadth to either of the individual antibodies, neutralizing 97% of viruses with a median 50% inhibitory concentration (IC50) of 0.055 mu g/ml. This bispecific IgG also demonstrated in vivo pharmacokinetic parameters comparable to those of the parental bNAbs when administered to rhesus macaques. These results suggest that IgG-based bispecific antibodies are promising candidates for the prevention and treatment of HIV-1 infection in humans.
IMPORTANCE
To prevent or treat HIV-1 infection, antibodies must potently neutralize nearly all strains of HIV-1. Thus, the physical combination of two or more antibodies may be needed to broaden neutralization coverage and diminish the possibility of viral resistance. A bispecific antibody that has two different antibody binding arms could potentially display neutralization characteristics better than those of any single parental antibody. Here we show that bispecific antibodies contain the binding specificities of the two parental antibodies and that a single bispecific antibody can neutralize 97% of viral strains with a high overall potency. These findings support the use of bispecific antibodies for the prevention or treatment of HIV-1 infection.
C1 [Asokan, M.; Rudicell, R. S.; Louder, M.; McKee, K.; O'Dell, S.; Stewart-Jones, G.; Wang, K.; Xu, L.; Chen, X.; Choe, M.; Chuang, G.; Georgiev, I. S.; Joyce, M. G.; Kirys, T.; Ko, S.; Pegu, A.; Shi, W.; Todd, J. P.; Yang, Z.; Bailer, R. T.; Rao, S.; Kwong, P. D.; Nabel, G. J.; Mascola, J. R.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
RP Mascola, JR (reprint author), NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM jmascola@nih.gov
FU intramural research program of the Vaccine Research Center, NIAID, NIH
FX This work was funded by the intramural research program of the Vaccine
Research Center, NIAID, NIH.
NR 41
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PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
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JI J. Virol.
PD DEC
PY 2015
VL 89
IS 24
BP 12501
EP 12512
DI 10.1128/JVI.02097-15
PG 12
WC Virology
SC Virology
GA CZ1WS
UT WOS:000366897200025
PM 26446600
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PT J
AU Ahn, K
Kao, C
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Mentch, Frank
Hakonarson, Hakon
Rapoport, Judith
TI Neurodevelopmental Copy Number Variants and Clinical Risk: A Pediatric
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LA English
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CT 54th Annual Meeting of the American-College-of-Neuropsychopharmacology
(ACNP)
CY DEC 06-10, 2015
CL Hollywood, FL
SP Amer Coll Neuropsychopharmacol
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C1 [Ahn, Kwangmi; Kao, Charlly; Mentch, Frank; Hakonarson, Hakon; Rapoport, Judith] NIMH, Bethesda, MD 20892 USA.
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PY 2015
VL 40
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PT J
AU Alvarez, V
AF Alvarez, Veronica
TI Strengthening Accumbal Indirect Pathway Promotes Resilience to
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LA English
DT Meeting Abstract
CT 54th Annual Meeting of the American-College-of-Neuropsychopharmacology
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CL Hollywood, FL
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JI Neuropsychopharmacology
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PY 2015
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UT WOS:000366597700095
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PT J
AU Aponte, Y
AF Aponte, Yeka
TI A Novel Microendoscopy System for Functional Imaging of Circuits that
Drive Feeding-Reward Behaviors
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LA English
DT Meeting Abstract
CT 54th Annual Meeting of the American-College-of-Neuropsychopharmacology
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CY DEC 06-10, 2015
CL Hollywood, FL
SP Amer Coll Neuropsychopharmacol
C1 [Aponte, Yeka] NIDA, Baltimore, MD USA.
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J9 NEUROPSYCHOPHARMACOL
JI Neuropsychopharmacology
PD DEC
PY 2015
VL 40
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GA CY7OI
UT WOS:000366597700018
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PT J
AU Arcurio, L
Schwandt, M
Zhu, X
Momenan, R
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Schwandt, Melanie
Zhu, Xi
Momenan, Reza
Leggio, Lorenzo
TI Characterization and Associated Risk-Factors of a Human Model of
Chronic-Heavy-Intermittent-Drinking
SO NEUROPSYCHOPHARMACOLOGY
LA English
DT Meeting Abstract
CT 54th Annual Meeting of the American-College-of-Neuropsychopharmacology
(ACNP)
CY DEC 06-10, 2015
CL Hollywood, FL
SP Amer Coll Neuropsychopharmacol
DE alcohol use disorder; drinking; at-risk; epidemiology
C1 [Arcurio, Lindsay; Schwandt, Melanie; Zhu, Xi; Momenan, Reza; Leggio, Lorenzo] NIAAA, Bethesda, MD USA.
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JI Neuropsychopharmacology
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GA CY7OI
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PT J
AU Ballard, E
Cui, LH
Machado-Vieira, R
Zarate, C
Merikangas, K
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Cui, Lihong
Machado-Vieira, Rodrigo
Zarate, Carlos
Merikangas, Kathleen
TI Anxiety Disorders Underlie the Familial Transmission of Suicide Attempts
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CY DEC 06-10, 2015
CL Hollywood, FL
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RI MACHADO-VIEIRA, RODRIGO/D-8293-2012
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PY 2015
VL 40
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PT J
AU Blanco, C
Wall, M
Olfson, M
AF Blanco, Carlos
Wall, Melanie
Olfson, Mark
TI The Relationship between Pain and Prescription Drug Use Disorders: A
National Prospective Study
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C1 [Blanco, Carlos; Wall, Melanie; Olfson, Mark] NIDA, Washington, DC USA.
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VL 40
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PT J
AU Bonci, A
AF Bonci, Antonello
TI From Optogenetics to rTMS: A Clinical Trials on Cocaine Craving
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CL Hollywood, FL
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JI Neuropsychopharmacology
PD DEC
PY 2015
VL 40
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MA 28.1
BP S47
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GA CY7OI
UT WOS:000366597700094
ER
PT J
AU Brotman, M
Tseng, WL
Wiggins, J
Kircanski, K
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Frank, H
Pine, D
Leibenluft, E
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Tseng, Wan-Ling
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White, Lauren
Frank, Heather
Pine, Daniel
Leibenluft, Ellen
TI Neural Correlates of Attention Bias in Irritability and Anxiety
SO NEUROPSYCHOPHARMACOLOGY
LA English
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CT 54th Annual Meeting of the American-College-of-Neuropsychopharmacology
(ACNP)
CY DEC 06-10, 2015
CL Hollywood, FL
SP Amer Coll Neuropsychopharmacol
DE attentional bias; irritability; Anxiety; fMRI
C1 [Brotman, Melissa; Tseng, Wan-Ling; Wiggins, Jillian; Kircanski, Katharina; White, Lauren; Frank, Heather; Pine, Daniel; Leibenluft, Ellen] NIMH, Bethesda, MD 20892 USA.
RI Brotman, Melissa/H-7409-2013
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UT WOS:000366597700528
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PT J
AU Callicott, J
Dickinson, D
Weinberger, D
Berman, K
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Dickinson, Dwight
Weinberger, Daniel
Berman, Karen
TI General Intelligence and Associated fMRI Networks in Schizophrenia
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CL Hollywood, FL
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C1 [Callicott, Joseph; Dickinson, Dwight; Weinberger, Daniel; Berman, Karen] NIMH, Bethesda, MD 20892 USA.
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UT WOS:000366597700889
ER
PT J
AU Cameron, H
AF Cameron, Heather
TI Stress, Unpredictability, and the Role of Adult Neurogenesis in Response
to Threat
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CT 54th Annual Meeting of the American-College-of-Neuropsychopharmacology
(ACNP)
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CL Hollywood, FL
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C1 [Cameron, Heather] NIMH, Bethesda, MD 20892 USA.
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GA CY7OI
UT WOS:000366597700033
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PT J
AU Chaarani, B
Mackey, S
Spechler, P
Higgins, S
Potter, A
Althoff, R
Stein, E
Garavan, H
AF Chaarani, Bader
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Spechler, Phil
Higgins, Stephen
Potter, Alexandra
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Garavan, Hugh
CA IMAGEN Consortium
TI Gene X Smoking Interactions in the Ventromedial PFC: Alpha 5 Nicotinic
Cholinergic Receptor Gene Variation and Smoking Effects on Adolescent
Grey Matter
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CT 54th Annual Meeting of the American-College-of-Neuropsychopharmacology
(ACNP)
CY DEC 06-10, 2015
CL Hollywood, FL
SP Amer Coll Neuropsychopharmacol
DE nicotine addiction; vmPFC; nicotinic acetylcholine receptors; alpha 5
C1 [Chaarani, Bader; Mackey, Scott; Spechler, Phil; Higgins, Stephen; Potter, Alexandra; Althoff, Robert; Stein, Elliot; Garavan, Hugh; IMAGEN Consortium] NIDA, Baltimore, MD USA.
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PT J
AU Cuthbert, B
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TI Data Sharing at NIMH
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PT J
AU Dickinson, D
Pratt, D
Orel, J
Giangrande, E
Weinberger, DR
Berman, K
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Pratt, Danielle
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Giangrande, Evan
Weinberger, Daniel R.
Berman, Karen
TI Resolving "Deficit'' and "Distress'' Schizophrenia Subgroups from
Positive and Negative Syndrome Scale Data
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PT J
AU Driscoll, C
Lindell, S
Yepes, M
Miller-Cruse, I
Stephens, C
McDonnell, S
Barr, C
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Lindell, Stephen
Yepes, Maelys
Miller-Cruse, Isaac
Stephens, Clay
McDonnell, Sue
Barr, Christina
TI Oxytocin Receptor Gene (OXTR) Variation, Fear and Reward Sensitivity in
Rhesus Macaque and Non-Traditional Model Animals
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CL Hollywood, FL
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PT J
AU Edwards, E
AF Edwards, Emmeline
TI Complementary and Integrative Health Approaches for Mental Health
Conditions
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CL Hollywood, FL
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C1 [Edwards, Emmeline] NIH, Natl Ctr Complementary & Integrat Hlth, Bethesda, MD 20892 USA.
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PT J
AU Eisenberg, D
Ianni, A
Hegarty, C
Kohn, P
Gregory, M
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Masdeu, J
Berman, K
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Hegarty, Catherine
Kohn, Philip
Gregory, Michael
Czarapata, Jasmin
Masdeu, Joseph
Berman, Karen
TI Multi-Tracer Pet Characterization of Pre- and Post -Synaptic
Dopaminergic Systems
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CY DEC 06-10, 2015
CL Hollywood, FL
SP Amer Coll Neuropsychopharmacol
DE Dopamine; striatum; PET
ID BRAIN
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PT J
AU Enoch, MA
Hodgkinson, C
Shen, PH
Yuan, QP
Goldman, D
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Hodgkinson, Colin
Shen, Pei-Hong
Yuan, Qiaoping
Goldman, David
TI Genetic Influences on Resting EEG Alpha Power in an American Indian
Tribe
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PT J
AU Ernst, M
Davis, A
Grillon, C
AF Ernst, Monique
Davis, Andrew
Grillon, Christian
TI Methylphenidate Decreases Anxiety-Induced Impairment of Working Memory
Performance in Healthy Subjects
SO NEUROPSYCHOPHARMACOLOGY
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CY DEC 06-10, 2015
CL Hollywood, FL
SP Amer Coll Neuropsychopharmacol
DE Threat of Shock; Working Memory Capacity; stimulant; anxiety state;
propanolol
C1 [Ernst, Monique; Davis, Andrew; Grillon, Christian] NIMH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 2
U2 5
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0893-133X
EI 1740-634X
J9 NEUROPSYCHOPHARMACOL
JI Neuropsychopharmacology
PD DEC
PY 2015
VL 40
SU 1
MA T9
BP S276
EP S277
PG 2
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA CY7OI
UT WOS:000366597700480
ER
PT J
AU Farokhnia, M
Schwandt, ML
Hodgkinson, CA
Leggio, L
AF Farokhnia, Mehdi
Schwandt, Melanie L.
Hodgkinson, Colin A.
Leggio, Lorenzo
TI Genetic Variation of the GABA(B) Receptor in Individuals with Alcohol
Use Disorder and Association with Smoking Measures
SO NEUROPSYCHOPHARMACOLOGY
LA English
DT Meeting Abstract
CT 54th Annual Meeting of the American-College-of-Neuropsychopharmacology
(ACNP)
CY DEC 06-10, 2015
CL Hollywood, FL
SP Amer Coll Neuropsychopharmacol
DE GABAB; Alcohol dependence; Smoking; genetics
C1 [Farokhnia, Mehdi; Schwandt, Melanie L.; Hodgkinson, Colin A.; Leggio, Lorenzo] NIAAA, NIDA, Bethesda, MD USA.
RI Leggio, Lorenzo/M-2972-2016
NR 0
TC 0
Z9 0
U1 0
U2 2
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0893-133X
EI 1740-634X
J9 NEUROPSYCHOPHARMACOL
JI Neuropsychopharmacology
PD DEC
PY 2015
VL 40
SU 1
MA M259
BP S269
EP S270
PG 2
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA CY7OI
UT WOS:000366597700467
ER
PT J
AU Ferre, S
AF Ferre, Sergi
TI Changing Classical Pharmacology by Exploring the Allosteric Mechanisms
of Caffeine Within the Adenosine A2A-Dopamine D2 Receptor Heterotetramer
SO NEUROPSYCHOPHARMACOLOGY
LA English
DT Meeting Abstract
CT 54th Annual Meeting of the American-College-of-Neuropsychopharmacology
(ACNP)
CY DEC 06-10, 2015
CL Hollywood, FL
SP Amer Coll Neuropsychopharmacol
C1 [Ferre, Sergi] NIDA, Baltimore, MD USA.
NR 0
TC 0
Z9 0
U1 5
U2 5
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0893-133X
EI 1740-634X
J9 NEUROPSYCHOPHARMACOL
JI Neuropsychopharmacology
PD DEC
PY 2015
VL 40
SU 1
MA 31.2
BP S54
EP S54
PG 1
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA CY7OI
UT WOS:000366597700107
ER
PT J
AU Goldman, D
Kwako, L
de Wit, H
Ramchandani, V
Schwandt, M
Mason, B
Voon, V
AF Goldman, David
Kwako, Laura
de Wit, Harriet
Ramchandani, Vijay
Schwandt, Melanie
Mason, Barbara
Voon, Valerie
TI Addictions Neuroclinical Assessment: The Search Continues
SO NEUROPSYCHOPHARMACOLOGY
LA English
DT Meeting Abstract
CT 54th Annual Meeting of the American-College-of-Neuropsychopharmacology
(ACNP)
CY DEC 06-10, 2015
CL Hollywood, FL
SP Amer Coll Neuropsychopharmacol
C1 [Goldman, David; Kwako, Laura; de Wit, Harriet; Ramchandani, Vijay; Schwandt, Melanie; Mason, Barbara; Voon, Valerie] NIAAA, Rockville, MD 20852 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0893-133X
EI 1740-634X
J9 NEUROPSYCHOPHARMACOL
JI Neuropsychopharmacology
PD DEC
PY 2015
VL 40
SU 1
MA 51
BP S89
EP S89
PG 1
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA CY7OI
UT WOS:000366597700178
ER
PT J
AU Goldman, D
Spagnolo, P
Bonci, A
Aston-Jones, G
Robbins, T
Creed, M
Denys, D
Green, A
Holtzheimer, P
Abulseoud, O
Rezai, A
Mayberg, H
AF Goldman, David
Spagnolo, Primavera
Bonci, Antonelle
Aston-Jones, Gary
Robbins, Trevor
Creed, Meaghan
Denys, DAmiaan
Green, Alan
Holtzheimer, Paul
Abulseoud, Osama
Rezai, Ali
Mayberg, Helen
TI Neurocircuit-based Interventions in Addictions: When and How?
SO NEUROPSYCHOPHARMACOLOGY
LA English
DT Meeting Abstract
CT 54th Annual Meeting of the American-College-of-Neuropsychopharmacology
(ACNP)
CY DEC 06-10, 2015
CL Hollywood, FL
SP Amer Coll Neuropsychopharmacol
C1 [Goldman, David; Spagnolo, Primavera; Bonci, Antonelle; Aston-Jones, Gary; Robbins, Trevor; Creed, Meaghan; Denys, DAmiaan; Green, Alan; Holtzheimer, Paul; Abulseoud, Osama; Rezai, Ali; Mayberg, Helen] NIAAA, Rockville, MD 20852 USA.
NR 0
TC 0
Z9 0
U1 2
U2 2
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0893-133X
EI 1740-634X
J9 NEUROPSYCHOPHARMACOL
JI Neuropsychopharmacology
PD DEC
PY 2015
VL 40
SU 1
MA 43
BP S75
EP S75
PG 1
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA CY7OI
UT WOS:000366597700149
ER
PT J
AU Gowin, J
Coe, M
Schwandt, M
Tapocik, J
Sun, H
Singley, E
Eskay, R
Umhau, J
Heilig, M
Ramchandani, V
AF Gowin, Joshua
Coe, Marion
Schwandt, Melanie
Tapocik, Jenica
Sun, Hui
Singley, Erick
Eskay, Robert
Umhau, John
Heilig, Markus
Ramchandani, Vijay
TI The Role of mu-Opioid Receptor (OPRM1) Gene A118G Polymorphism on
Cortisol and beta-Endorphin Response to Alcohol
SO NEUROPSYCHOPHARMACOLOGY
LA English
DT Meeting Abstract
CT 54th Annual Meeting of the American-College-of-Neuropsychopharmacology
(ACNP)
CY DEC 06-10, 2015
CL Hollywood, FL
SP Amer Coll Neuropsychopharmacol
DE OPRM1 A118G; HPA axis; Opioid system; Alcohol
C1 [Gowin, Joshua; Coe, Marion; Schwandt, Melanie; Tapocik, Jenica; Sun, Hui; Singley, Erick; Eskay, Robert; Umhau, John; Heilig, Markus; Ramchandani, Vijay] NIAAA, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0893-133X
EI 1740-634X
J9 NEUROPSYCHOPHARMACOL
JI Neuropsychopharmacology
PD DEC
PY 2015
VL 40
SU 1
MA T224
BP S417
EP S418
PG 2
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA CY7OI
UT WOS:000366597700691
ER
PT J
AU Grant, S
Pariyadath, V
Chiu, P
Childress, AR
Breiter, H
Evins, A
George, M
Mackey, S
Zubieta, JK
AF Grant, Steven
Pariyadath, Vani
Chiu, Pearl
Childress, Anna Rose
Breiter, Hans
Evins, Anne
George, Mark
Mackey, Sean
Zubieta, Jon-Kar
TI rt-fMRI Neurofeedback: Are We There Yet?
SO NEUROPSYCHOPHARMACOLOGY
LA English
DT Meeting Abstract
CT 54th Annual Meeting of the American-College-of-Neuropsychopharmacology
(ACNP)
CY DEC 06-10, 2015
CL Hollywood, FL
SP Amer Coll Neuropsychopharmacol
C1 [Grant, Steven; Pariyadath, Vani; Chiu, Pearl; Childress, Anna Rose; Breiter, Hans; Evins, Anne; George, Mark; Mackey, Sean; Zubieta, Jon-Kar] NIDA, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 2
U2 2
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0893-133X
EI 1740-634X
J9 NEUROPSYCHOPHARMACOL
JI Neuropsychopharmacology
PD DEC
PY 2015
VL 40
SU 1
MA 17
BP S28
EP S28
PG 1
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA CY7OI
UT WOS:000366597700058
ER
PT J
AU Gregory, MD
Kippenhan, JS
Nash, T
Prabhakaran, R
Eisenberg, D
Yankowitz, L
Insel, C
Roe, K
Sottile, M
Kohn, P
Mervis, C
Berman, K
AF Gregory, Michael D.
Kippenhan, J. Shane
Nash, Tiffany
Prabhakaran, Ranjani
Eisenberg, Daniel
Yankowitz, Lisa
Insel, Crystal
Roe, Katherine
Sottile, Melanie
Kohn, Philip
Mervis, Carolyn
Berman, Karen
TI Copy Number Variation of the 7q11.23 Williams Syndrome Chromosomal
Region Affects Brain Gyrification and Skull Shape
SO NEUROPSYCHOPHARMACOLOGY
LA English
DT Meeting Abstract
CT 54th Annual Meeting of the American-College-of-Neuropsychopharmacology
(ACNP)
CY DEC 06-10, 2015
CL Hollywood, FL
SP Amer Coll Neuropsychopharmacol
DE Dup7; gyrification; skull shape; williams syndrome; 7q11.23
C1 [Gregory, Michael D.; Kippenhan, J. Shane; Nash, Tiffany; Prabhakaran, Ranjani; Eisenberg, Daniel; Yankowitz, Lisa; Insel, Crystal; Roe, Katherine; Sottile, Melanie; Kohn, Philip; Mervis, Carolyn; Berman, Karen] NIMH, Bethesda, MD 20892 USA.
RI Eisenberg, Daniel/S-4342-2016
NR 10
TC 0
Z9 0
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0893-133X
EI 1740-634X
J9 NEUROPSYCHOPHARMACOL
JI Neuropsychopharmacology
PD DEC
PY 2015
VL 40
SU 1
MA W28
BP S460
EP S461
PG 2
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA CY7OI
UT WOS:000366597700756
ER
PT J
AU Heilig, M
AF Heilig, Markus
TI The Role of Epigenetic Mechanisms in the Medial Prefrontal Cortex in the
Transition to Alcohol Dependence
SO NEUROPSYCHOPHARMACOLOGY
LA English
DT Meeting Abstract
CT 54th Annual Meeting of the American-College-of-Neuropsychopharmacology
(ACNP)
CY DEC 06-10, 2015
CL Hollywood, FL
SP Amer Coll Neuropsychopharmacol
C1 [Heilig, Markus] NIAAA, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0893-133X
EI 1740-634X
J9 NEUROPSYCHOPHARMACOL
JI Neuropsychopharmacology
PD DEC
PY 2015
VL 40
SU 1
MA 11.1
BP S17
EP S18
PG 2
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA CY7OI
UT WOS:000366597700036
ER
PT J
AU Hickie, I
Scott, E
Merikangas, K
AF Hickie, Ian
Scott, Elizabeth
Merikangas, Kathleen
TI Use of Mobile Technologies to Monitor Activity, Sleep, and Mood States
to Identify Targets of Prevention of Mood Disorders
SO NEUROPSYCHOPHARMACOLOGY
LA English
DT Meeting Abstract
CT 54th Annual Meeting of the American-College-of-Neuropsychopharmacology
(ACNP)
CY DEC 06-10, 2015
CL Hollywood, FL
SP Amer Coll Neuropsychopharmacol
DE Mobile technology; accelerometry; mood disorders; big data; Actigraphy;
mood and anxiety disorders
C1 [Hickie, Ian; Scott, Elizabeth; Merikangas, Kathleen] NIMH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 4
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0893-133X
EI 1740-634X
J9 NEUROPSYCHOPHARMACOL
JI Neuropsychopharmacology
PD DEC
PY 2015
VL 40
SU 1
MA W105
BP S507
EP S508
PG 2
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA CY7OI
UT WOS:000366597700829
ER
PT J
AU Hodgkinson, C
Perez-Rodriguez, MM
Yuan, QP
Leung, M
Prat, M
Casas, M
Ferrer, M
Ribases, M
Andion, O
New, A
Siever, L
Goldman, D
AF Hodgkinson, Colin
Perez-Rodriguez, M. Mercedes
Yuan, Qiaoping
Leung, Ming
Prat, Monica
Casas, Miguel
Ferrer, Marc
Ribases, Marta
Andion, Oscar
New, Antonia
Siever, Larry
Goldman, David
TI Exome Sequencing of Borderline Personality Disorder Patients to Identify
Functional Rare Variants
SO NEUROPSYCHOPHARMACOLOGY
LA English
DT Meeting Abstract
CT 54th Annual Meeting of the American-College-of-Neuropsychopharmacology
(ACNP)
CY DEC 06-10, 2015
CL Hollywood, FL
SP Amer Coll Neuropsychopharmacol
DE exome; borderline personaility disorder; sequencing
C1 [Hodgkinson, Colin; Perez-Rodriguez, M. Mercedes; Yuan, Qiaoping; Leung, Ming; Prat, Monica; Casas, Miguel; Ferrer, Marc; Ribases, Marta; Andion, Oscar; New, Antonia; Siever, Larry; Goldman, David] NIAAA, Rockville, MD 20852 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0893-133X
EI 1740-634X
J9 NEUROPSYCHOPHARMACOL
JI Neuropsychopharmacology
PD DEC
PY 2015
VL 40
SU 1
MA W148
BP S536
EP S536
PG 1
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA CY7OI
UT WOS:000366597700872
ER
PT J
AU Hoffman, J
Dubey, N
Schuebel, K
Marietta, C
Yuan, QP
Martinez, P
Nieman, L
Rubinow, D
Schmidt, P
Goldman, D
AF Hoffman, Jessica
Dubey, Neelima
Schuebel, Kornel
Marietta, Cheryl
Yuan, Qiaoping
Martinez, Pedro
Nieman, Lynnette
Rubinow, David
Schmidt, Peter
Goldman, David
TI Lymphoblast Cell Lines from Women with Premenstrual Dysphoric Disorder
(PMDD) Differ in mRNA and Protein Expression Profiles of the ESC/E(Z)
Pathway Compared with Asymptomatic Controls
SO NEUROPSYCHOPHARMACOLOGY
LA English
DT Meeting Abstract
CT 54th Annual Meeting of the American-College-of-Neuropsychopharmacology
(ACNP)
CY DEC 06-10, 2015
CL Hollywood, FL
SP Amer Coll Neuropsychopharmacol
DE mood disorder; ovarian steroids; Whole exome sequencing; RNA Sequencing;
premenstrual dysphoric disorder
C1 [Hoffman, Jessica; Dubey, Neelima; Schuebel, Kornel; Marietta, Cheryl; Yuan, Qiaoping; Martinez, Pedro; Nieman, Lynnette; Rubinow, David; Schmidt, Peter; Goldman, David] NIMH, Rockville, MD 20857 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0893-133X
EI 1740-634X
J9 NEUROPSYCHOPHARMACOL
JI Neuropsychopharmacology
PD DEC
PY 2015
VL 40
SU 1
MA M116
BP S180
EP S181
PG 2
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA CY7OI
UT WOS:000366597700324
ER
PT J
AU Iadarola, M
Sapio, M
Mannes, A
AF Iadarola, Michael
Sapio, Matthew
Mannes, Andrew
TI Nociceptive Neural Transcriptional Plasticity in Rat Dorsal Horn in a
Persistent Pain Model
SO NEUROPSYCHOPHARMACOLOGY
LA English
DT Meeting Abstract
CT 54th Annual Meeting of the American-College-of-Neuropsychopharmacology
(ACNP)
CY DEC 06-10, 2015
CL Hollywood, FL
SP Amer Coll Neuropsychopharmacol
DE chronic pain; gene expression; Transcriptomics; transcription factors;
Synaptic Plasticity
C1 [Iadarola, Michael; Sapio, Matthew; Mannes, Andrew] NIH, Bethesda, MD 20892 USA.
RI Sapio, Matthew/J-5096-2016
OI Sapio, Matthew/0000-0002-8855-5419
NR 0
TC 0
Z9 0
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0893-133X
EI 1740-634X
J9 NEUROPSYCHOPHARMACOL
JI Neuropsychopharmacology
PD DEC
PY 2015
VL 40
SU 1
MA W143
BP S532
EP S533
PG 2
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA CY7OI
UT WOS:000366597700867
ER
PT J
AU Ianni, A
Eisenberg, D
Hegarty, C
Masdeu, J
Gregory, M
Kohn, P
Berman, K
AF Ianni, Angela
Eisenberg, Daniel
Hegarty, Catherine
Masdeu, Joseph
Gregory, Michael
Kohn, Philip
Berman, Karen
TI Dopamine Synthesis and Receptor Profile are Associated with Body Mass
Index in Humans
SO NEUROPSYCHOPHARMACOLOGY
LA English
DT Meeting Abstract
CT 54th Annual Meeting of the American-College-of-Neuropsychopharmacology
(ACNP)
CY DEC 06-10, 2015
CL Hollywood, FL
SP Amer Coll Neuropsychopharmacol
DE Dopamine; Obesity; Neuroreceptor imaging
C1 [Ianni, Angela; Eisenberg, Daniel; Hegarty, Catherine; Masdeu, Joseph; Gregory, Michael; Kohn, Philip; Berman, Karen] NIH, Bethesda, MD 20892 USA.
RI Eisenberg, Daniel/S-4342-2016
NR 0
TC 0
Z9 0
U1 2
U2 4
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0893-133X
EI 1740-634X
J9 NEUROPSYCHOPHARMACOL
JI Neuropsychopharmacology
PD DEC
PY 2015
VL 40
SU 1
MA W45
BP S472
EP S473
PG 2
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA CY7OI
UT WOS:000366597700773
ER
PT J
AU Ihne, J
Nugent, A
Furey, M
Szczepanik, J
Zarate, C
AF Ihne, Jessica
Nugent, Alli