FN Thomson Reuters Web of Science™
VR 1.0
PT J
AU Bousfiha, A
Jeddane, L
Al-Herz, W
Ailal, F
Casanova, JL
Chatila, T
Conley, ME
Cunningham-Rundles, C
Etzioni, A
Franco, JL
Gaspar, HB
Holland, SM
Klein, C
Nonoyama, S
Ochs, HD
Oksenhendler, E
Picard, C
Puck, JM
Sullivan, KE
Tang, MLK
AF Bousfiha, Aziz
Jeddane, Leila
Al-Herz, Waleed
Ailal, Fatima
Casanova, Jean-Laurent
Chatila, Talal
Conley, Mary Ellen
Cunningham-Rundles, Charlotte
Etzioni, Amos
Franco, Jose Luis
Gaspar, H. Bobby
Holland, Steven M.
Klein, Christoph
Nonoyama, Shigeaki
Ochs, Hans D.
Oksenhendler, Eric
Picard, Capucine
Puck, Jennifer M.
Sullivan, Kathleen E.
Tang, Mimi L. K.
TI The 2015 IUIS Phenotypic Classification for Primary Immunodeficiencies
SO JOURNAL OF CLINICAL IMMUNOLOGY
LA English
DT Article
DE Primary immunodeficiencies; classification; IUIS PID expert committee
ID DIAGNOSIS; DEFICIENCY; WORLDWIDE; DISEASES
AB There are now nearly 300 single-gene inborn errors of immunity underlying phenotypes as diverse as infection, malignancy, allergy, auto-immunity, and auto-inflammation. For each of these five categories, a growing variety of phenotypes are ascribed to Primary Immunodeficiency Diseases (PID), making PIDs a rapidly expanding field of medicine. The International Union of Immunological Societies (IUIS) PID expert committee (EC) has published every other year a classification of these disorders into tables, defined by shared pathogenesis and/or clinical consequences. In 2013, the IUIS committee also proposed a more user-friendly, phenotypic classification, based on the selection of key phenotypes at the bedside. We herein propose the revised figures, based on the accompanying 2015 IUIS PID EC classification.
C1 [Bousfiha, Aziz; Jeddane, Leila; Ailal, Fatima] King Hassan II Univ, Clin Immunol Unit, A Harouchi Hosp, Ibn Roshd Med Sch, Casablanca, Morocco.
[Al-Herz, Waleed] Kuwait Univ, Fac Med, Dept Pediat, Jabriya, Kuwait.
[Al-Herz, Waleed] Al Sabah Hosp, Allergy & Clin Immunol Unit, Dept Pediat, Kuwait, Kuwait.
[Casanova, Jean-Laurent; Conley, Mary Ellen] Rockefeller Univ, St Giles Lab Human Genet Infect Dis, Rockefeller Branch, New York, NY 10021 USA.
[Casanova, Jean-Laurent; Picard, Capucine] Howard Hughes Med Inst, New York, NY USA.
[Casanova, Jean-Laurent] Necker Hosp Sick Children, Lab Human Genet Infect Dis, Necker Branch, INSERM UMR1163, Paris, France.
[Casanova, Jean-Laurent] Univ Paris 05, Imagine Inst, Paris, France.
[Casanova, Jean-Laurent] Necker Hosp Sick Children, Pediat Hematol & Immunol Unit, Paris, France.
[Chatila, Talal] Childrens Hosp, Div Immunol, Boston, MA 02115 USA.
[Cunningham-Rundles, Charlotte] Mt Sinai Sch Med, Dept Med & Pediat, New York, NY USA.
[Etzioni, Amos] Technion Israel Inst Technol, Meyer Childrens Hospital, Haifa, Israel.
[Franco, Jose Luis] Univ Antioquia, Grp Primary Immunodeficiencies, Medellin, Colombia.
[Gaspar, H. Bobby] UCL Inst Child Hlth, London, England.
[Holland, Steven M.] NIAID, Lab Clin Infect Dis, Bethesda, MD 20892 USA.
[Klein, Christoph] Univ Munich, Dr von Hauner Childrens Hosp, Munich, Germany.
[Nonoyama, Shigeaki] Natl Def Med Coll, Dept Pediat, Saitama, Japan.
[Ochs, Hans D.] Univ Washington, Dept Pediat, Seattle, WA 98195 USA.
[Ochs, Hans D.] Seattle Childrens Res Inst, Seattle, WA USA.
[Oksenhendler, Eric] Hop St Louis, AP HP, Dept Clin Immunol, Paris, France.
[Oksenhendler, Eric] Univ Paris Diderot, Sorbonne Paris Cite, Paris, France.
[Picard, Capucine] Hop Necker Enfants Malad, AP HP, Ctr Etude Deficits Immunitaires, Paris, France.
[Puck, Jennifer M.] Univ Calif San Francisco, Dept Pediat, San Francisco, CA USA.
[Puck, Jennifer M.] UCSF Benioff Childrens Hosp, San Francisco, CA USA.
[Sullivan, Kathleen E.] Childrens Hosp Philadelphia, Dept Pediat, Div Allergy Immunol, Philadelphia, PA 19104 USA.
[Tang, Mimi L. K.] Murdoch Childrens Res Inst, Melbourne, Vic, Australia.
[Tang, Mimi L. K.] Univ Melbourne, Dept Paediat, Melbourne, Vic, Australia.
[Tang, Mimi L. K.] Royal Childrens Hosp, Dept Allergy & Immunol, Melbourne, Vic, Australia.
RP Bousfiha, A (reprint author), King Hassan II Univ, Clin Immunol Unit, A Harouchi Hosp, Ibn Roshd Med Sch, Casablanca, Morocco.
EM profbousfiha@gmail.com
FU NIAID NIH HHS [R18 AI048693]
NR 9
TC 33
Z9 34
U1 3
U2 5
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0271-9142
EI 1573-2592
J9 J CLIN IMMUNOL
JI J. Clin. Immunol.
PD NOV
PY 2015
VL 35
IS 8
BP 727
EP 738
DI 10.1007/s10875-015-0198-5
PG 12
WC Immunology
SC Immunology
GA CX7HN
UT WOS:000365872900004
PM 26445875
ER
PT J
AU Shallom, SJ
Moura, NS
Olivier, KN
Sampaio, EP
Holland, SM
Zelazny, AM
AF Shallom, Shamira J.
Moura, Natalia S.
Olivier, Kenneth N.
Sampaio, Elizabeth P.
Holland, Steven M.
Zelazny, Adrian M.
TI New Real-Time PCR Assays for Detection of Inducible and Acquired
Clarithromycin Resistance in the Mycobacterium abscessus Group
SO JOURNAL OF CLINICAL MICROBIOLOGY
LA English
DT Article
ID MACROLIDE RESISTANCE; CYSTIC-FIBROSIS; MASSILIENSE; SUSCEPTIBILITY;
CHELONAE; COHORT; GENE; IDENTIFICATION; INFECTIONS; DIAGNOSIS
AB Members of the Mycobacterium abscessus group (MAG) cause lung, soft tissue, and disseminated infections. The oral macrolides clarithromycin and azithromycin are commonly used for treatment. MAG can display clarithromycin resistance through the inducible erm (41) gene or via acquired mutations in the rrl (23S rRNA) gene. Strains harboring a truncation or a T28C substitution in erm (41) lose the inducible resistance trait. Phenotypic detection of clarithromycin resistance requires extended incubation (14 days), highlighting the need for faster methods to detect resistance. Two real-time PCR-based assays were developed to assess inducible and acquired clarithromycin resistance and tested on a total of 90 clinical and reference strains. A SYBR green assay was designed to distinguish between a full-length and truncated erm (41) gene by temperature shift in melting curve analysis. Single nucleotide polymorphism (SNP) allele discrimination assays were developed to distinguish T or C at position 28 of erm (41) and 23S rRNA rrl gene mutations at position 2058 and/or 2059. Truncated and full-size erm (41) genes were detected in 21/90 and 69/90 strains, respectively, with 64/69 displaying T at nucleotide position 28 and 5/69 containing C at that position. Fifteen isolates showed rrl mutations conferring clarithromycin resistance, including A2058G (11 isolates), A2058C (3 isolates), and A2059G (1 isolate). Targeted sequencing and phenotypic assessment of resistance concurred with molecular assay results. Interestingly, we also noted cooccurring strains harboring an active erm (41), inactive erm (41), and/or acquired mutational resistance, as well as slowly growing MAG strains and also strains displaying an inducible resistance phenotype within 5 days, long before the recommended 14-day extended incubation.
C1 [Shallom, Shamira J.; Moura, Natalia S.; Zelazny, Adrian M.] NIH, Microbiol Serv, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA.
[Olivier, Kenneth N.] NHLBI, Cardiovasc & Pulm Branch, NIH, Bethesda, MD 20892 USA.
[Sampaio, Elizabeth P.; Holland, Steven M.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
[Sampaio, Elizabeth P.] Fiocruz MS, Inst Oswaldo Cruz, Leprosy Lab, BR-21045900 Rio De Janeiro, Brazil.
RP Zelazny, AM (reprint author), NIH, Microbiol Serv, Dept Lab Med, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA.
EM azelazny@mail.nih.gov
FU Intramural Research Programs of the Clinical Center, NIAID; NHLBI; NIH
FX This research was supported in part by the Intramural Research Programs
of the Clinical Center, NIAID, and NHLBI, NIH.
NR 29
TC 4
Z9 4
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 NOV
PY 2015
VL 53
IS 11
BP 3430
EP 3437
DI 10.1128/JCM.01714-15
PG 8
WC Microbiology
SC Microbiology
GA CX3UY
UT WOS:000365626200009
PM 26269619
ER
PT J
AU Park, IK
Hsu, AP
Tettelin, H
Shallom, SJ
Drake, SK
Ding, L
Wu, UI
Adamo, N
Prevots, DR
Olivier, KN
Holland, SM
Sampaio, EP
Zelazny, AM
AF Park, In Kwon
Hsu, Amy P.
Tettelin, Herve
Shallom, Shamira J.
Drake, Steven K.
Ding, Li
Wu, Un-In
Adamo, Nick
Prevots, D. Rebecca
Olivier, Kenneth N.
Holland, Steven M.
Sampaio, Elizabeth P.
Zelazny, Adrian M.
TI Clonal Diversification and Changes in Lipid Traits and Colony Morphology
in Mycobacterium abscessus Clinical Isolates
SO JOURNAL OF CLINICAL MICROBIOLOGY
LA English
DT Article
ID NONTUBERCULOUS MYCOBACTERIA; CYSTIC-FIBROSIS; SP-NOV; BIOSYNTHESIS;
TUBERCULOSIS; MASSILIENSE; ROUGH; EPIDEMIOLOGY; PHAGOCYTOSIS; MEMBRANE
AB The smooth-to-rough colony morphology shift in Mycobacterium abscessus has been implicated in loss of glycopeptidolipid (GPL), increased pathogenicity, and clinical decline in cystic fibrosis (CF) patients. However, the evolutionary phenotypic and genetic changes remain obscure. Serial isolates from nine non-CF patients with persistent M. abscessus infection were characterized by colony morphology, lipid profile via thin-layer chromatography and matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS), sequencing of eight genes in the GPL locus, and expression level of fadD23, a key gene involved in the biosynthesis of complex lipids. All 50 isolates were typed as M. abscessus subspecies abscessus and were clonally related within each patient. Rough isolates, all lacking GPL, predominated at later disease stages, some showing variation within rough morphology. While most (77%) rough isolates harbored detrimental mutations in mps1 and mps2, 13% displayed previously unreported mutations in mmpL4a and mmpS4, the latter yielding a putative GPL precursor. Two isolates showed no deleterious mutations in any of the eight genes sequenced. Mixed populations harboring different GPL locus mutations were detected in 5 patients, demonstrating clonal diversification, which was likely overlooked by conventional acid-fast bacillus (AFB) culture methods. Our work highlights applications of MALDI-TOF MS beyond identification, focusing on mycobacterial lipids relevant in virulence and adaptation. Later isolates displayed accumulation of triacylglycerol and reduced expression of fadD23, sometimes preceding rough colony onset. Our results indicate that clonal diversification and a shift in lipid metabolism, including the loss of GPL, occur during chronic lung infection with M. abscessus. GPL loss alone may not account for all traits associated with rough morphology.
C1 [Park, In Kwon; Hsu, Amy P.; Ding, Li; Wu, Un-In; Adamo, Nick; Prevots, D. Rebecca; Holland, Steven M.; Sampaio, Elizabeth P.; Zelazny, Adrian M.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
[Tettelin, Herve] Univ Maryland, Sch Med, Inst Genome Sci, Baltimore, MD 21201 USA.
[Shallom, Shamira J.; Zelazny, Adrian M.] NIH, Microbiol Serv, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA.
[Drake, Steven K.] NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA.
[Olivier, Kenneth N.] NHLBI, Pulm Clin Med Sect, Cardiovasc & Pulm Branch, NIH, Bethesda, MD 20892 USA.
[Sampaio, Elizabeth P.] Fiocruz MS, Inst Oswaldo Cruz, Leprosy Lab, BR-21045900 Rio De Janeiro, Brazil.
RP Zelazny, AM (reprint author), NIAID, Lab Clin Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM azelazny@mail.nih.gov
OI WU, UN-IN/0000-0001-8182-6071
FU Divisions of Intramural Research of the National Institute of Allergy
and Infectious Diseases; National Heart, Lung and Blood Institute;
Clinical Center, National Institutes of Health
FX This work was supported by the Divisions of Intramural Research of the
National Institute of Allergy and Infectious Diseases, the National
Heart, Lung and Blood Institute, and the Clinical Center, National
Institutes of Health.
NR 35
TC 7
Z9 7
U1 2
U2 4
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 NOV
PY 2015
VL 53
IS 11
BP 3438
EP 3447
DI 10.1128/JCM.02015-15
PG 10
WC Microbiology
SC Microbiology
GA CX3UY
UT WOS:000365626200010
PM 26292297
ER
PT J
AU Liu, X
Schiffman, M
Hulbert, A
He, ZH
Shen, ZP
Koutsky, LA
Xi, LF
AF Liu, Xia
Schiffman, Mark
Hulbert, Ayaka
He, Zhonghu
Shen, Zhenping
Koutsky, Laura A.
Xi, Long Fu
TI Association of Human Papillomavirus 31 DNA Load with Risk of Cervical
Intraepithelial Neoplasia Grades 2 and 3
SO JOURNAL OF CLINICAL MICROBIOLOGY
LA English
DT Article
ID VIRAL LOAD; NATURAL-HISTORY; IN-SITU; CANCER; INFECTION; LESIONS; WOMEN;
CLEARANCE; DISEASE; INTEGRATION
AB The association between human papillomavirus 31 (HPV31) DNA loads and the risk of cervical intraepithelial neoplasia grades 2 and 3 (CIN2-3) was evaluated among women enrolled in the atypical squamous cells of undetermined significance (ASCUS) and low-grade squamous intraepithelial lesion (LSIL) triage study (ALTS), who were monitored semiannually over 2 years and who had HPV31 infections detected at >= 1 visit. HPV31 DNA loads in the first HPV31-positive samples and in a random set of the last positive samples from women with >= 2 HPV31-positive visits were measured by a real-time PCR assay. CIN2-3 was histologically confirmed at the same time as the first detection of HPV31 for 88 (16.6%) of 530 women. After adjustment for HPV31 lineages, coinfection with other oncogenic types, and the timing of the first positive detection, the odds ratio (OR) per 1-log-unit increase in viral loads for the risk of a concurrent diagnosis of CIN2-3 was 1.5 (95% confidence interval [CI], 1.2 to 1.9). Of 373 women without CIN2-3 at the first positive visit who had >= 1 later visit, 44 had subsequent diagnoses of CIN2-3. The initial viral loads were associated with CIN2-3 diagnosed within 6 months after the first positive visit (adjusted OR, 1.5 [95% CI, 1.0 to 2.4]) but were unrelated to CIN2-3 diagnosed later. For a random set of 49 women who were tested for viral loads at the first and last positive visits, changes in viral loads were upward and downward among women with and without follow-up CIN2-3 diagnoses, respectively, although the difference was not statistically significant. Results suggest that HPV31 DNA load levels at the first positive visit signal a short-term but not long-term risk of CIN2-3.
C1 [Liu, Xia; Hulbert, Ayaka; Shen, Zhenping; Xi, Long Fu] Univ Washington, Sch Med, Dept Pathol, Seattle, WA 98195 USA.
[Koutsky, Laura A.; Xi, Long Fu] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA.
[Schiffman, Mark] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Liu, Xia] China Med Univ, Shengjing Hosp, Dept Obstet & Gynecol, Liaoning, Peoples R China.
[He, Zhonghu] Peking Univ, Sch Oncol, Key Lab Carcinogenesis & Translat Res, Beijing 100871, Peoples R China.
RP Xi, LF (reprint author), Univ Washington, Sch Med, Dept Pathol, Seattle, WA 98195 USA.
EM longfu@u.washington.edu
FU National Cancer Institute, National Institutes of Health [CA133569];
Plan of Cultivating Future Talents award from Shengjing Hospital, China
Medical University
FX The research reported in this publication was supported by the National
Cancer Institute, National Institutes of Health (grant CA133569). X.L.
was financially supported by a Plan of Cultivating Future Talents award
from Shengjing Hospital, China Medical University.
NR 32
TC 0
Z9 0
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 NOV
PY 2015
VL 53
IS 11
BP 3451
EP 3457
DI 10.1128/JCM.01279-15
PG 7
WC Microbiology
SC Microbiology
GA CX3UY
UT WOS:000365626200012
PM 26292291
ER
PT J
AU Sarkar, S
Rivera, EM
Engle, RE
Nguyen, HT
Schechterly, CA
Alter, HJ
Liang, TJ
Purcell, RH
Hoofnagle, JH
Ghany, MG
AF Sarkar, Souvik
Rivera, Elenita M.
Engle, Ronald E.
Nguyen, Hanh T.
Schechterly, Cathy A.
Alter, Harvey J.
Liang, T. Jake
Purcell, Robert H.
Hoofnagle, Jay H.
Ghany, Marc G.
TI An Epidemiologic Investigation of a Case of Acute Hepatitis E
SO JOURNAL OF CLINICAL MICROBIOLOGY
LA English
DT Article
ID E VIRUS-INFECTION; ORGAN-TRANSPLANT RECIPIENTS; UNITED-STATES;
ENZYME-IMMUNOASSAY; NATIONAL-HEALTH; BLOOD-DONORS; ANTIBODIES; FRANCE;
SWINE; HEV
AB Hepatitis E virus (HEV) is considered a zoonotic infection in developed nations. A case of acute hepatitis E in a researcher following a scalpel injury while working on a pig prompted a seroepidemiologic study to identify potential modes of transmission and determine the seroprevalence of HEV among animal handlers at the institute. Sera from personnel (n = 64) in two animal facilities and age/sex-matched blood donors (n = 63) as controls were tested for IgG anti-HEV and, if positive, for IgM anti-HEV and HEV RNA. Sera and stool from pigs aged 6 to 12 weeks from the breeding farm and older pigs from animal facilities were tested similarly. The median age of personnel was 36 years, 74% were white, 56% were male, and 74% had direct exposure to pigs. The prevalence of anti-HEV was 3.1% among personnel compared to 3.2% among blood donors; none were positive for IgM anti-HEV or HEV RNA. IgG anti-HEV was detected in sera from 10% of pigs aged 6 to 8 weeks, 80% aged 10 weeks, 100% aged 12 weeks, and 76% aged >12 weeks. HEV RNA was detected in stool but not sera from three 12-week-old pigs. Sequencing revealed HEV genotype 3 with similar to 10% difference between the patient and pig sequences. Parenteral transmission is a potential mode of acute HEV infection. The low and similar seroprevalence of anti-HEV between the at-risk group and age-matched blood donors suggests low transmission risk with universal precautions among animal handlers.
C1 [Sarkar, Souvik; Rivera, Elenita M.; Liang, T. Jake; Ghany, Marc G.] NIDDK, Liver Dis Branch, NIH, Bethesda, MD 20892 USA.
[Engle, Ronald E.; Nguyen, Hanh T.; Purcell, Robert H.] NIAID, Hepatitis Viruses Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
[Schechterly, Cathy A.; Alter, Harvey J.] NIH, Transfus Transmitted Viruses Lab, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA.
[Hoofnagle, Jay H.] NIDDK, Liver Dis Res Branch, Div Digest Dis & Nutr, NIH, Bethesda, MD 20892 USA.
RP Ghany, MG (reprint author), NIDDK, Liver Dis Branch, NIH, Bethesda, MD 20892 USA.
EM marcg@intra.niddk.nih.gov
OI Sarkar, Souvik/0000-0002-9358-4257
FU Intramural Research Program of NIAID; Intramural Research Program of
NIDDK
FX This research was supported by the Intramural Research Programs of NIAID
and NIDDK.
NR 37
TC 0
Z9 1
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 NOV
PY 2015
VL 53
IS 11
BP 3547
EP 3552
DI 10.1128/JCM.01189-15
PG 6
WC Microbiology
SC Microbiology
GA CX3UY
UT WOS:000365626200026
PM 26338861
ER
PT J
AU Mikhail, AS
Partanen, A
Yarmolenko, P
Venkatesan, AM
Wood, BJ
AF Mikhail, Andrew S.
Partanen, Ari
Yarmolenko, Pavel
Venkatesan, Aradhana M.
Wood, Bradford J.
TI Magnetic Resonance-Guided Drug Delivery
SO MAGNETIC RESONANCE IMAGING CLINICS OF NORTH AMERICA
LA English
DT Article
DE MR imaging; Drug delivery; Tumor targeting; Nanomedicine; Cancer;
Thermosensitive liposome; High-intensity focused ultrasound; Imaging
guidance
ID INTENSITY FOCUSED ULTRASOUND; TEMPERATURE-SENSITIVE LIPOSOMES; HUMAN
TUMOR XENOGRAFT; NONINVASIVE FUNCTIONAL NEUROSURGERY; SOLID TUMORS;
THERMOSENSITIVE LIPOSOMES; CANCER-THERAPY; HIFU ABLATION; ANIMAL-MODELS;
VX2 TUMORS
AB The use of clinical imaging modalities for the guidance of targeted drug delivery systems, known as image-guided drug delivery (IGDD), has emerged as a promising strategy for enhancing antitumor efficacy. Magnetic resonance (MR) imaging is particularly well suited for IGDD applications because of its ability to acquire images and quantitative measurements with high spatiotemporal resolution. The goal of IGDD strategies is to improve treatment outcomes by facilitating planning, real-time guidance, and personalization of pharmacologic interventions. This article reviews basic principles of targeted drug delivery and highlights the current status, emerging applications, and future paradigms of MR-guided drug delivery.
C1 [Mikhail, Andrew S.; Partanen, Ari; Wood, Bradford J.] NIH, Ctr Intervent Oncol, Dept Radiol & Imaging Sci, Ctr Clin, Bethesda, MD 20892 USA.
[Partanen, Ari] Philips Healthcare, Andover, MA 01810 USA.
[Yarmolenko, Pavel] Childrens Natl Med Ctr, Sheikh Zayed Inst Pediat Surg Innovat, Washington, DC 20010 USA.
[Venkatesan, Aradhana M.] MD Anderson Canc Ctr, Dept Diagnost Radiol, Sect Abdominal Imaging, Houston, TX 77030 USA.
RP Wood, BJ (reprint author), NIH, Ctr Intervent Oncol, Dept Radiol & Imaging Sci, Ctr Clin, 10 Ctr Dr, Bethesda, MD 20892 USA.
EM bwood@nih.gov
OI Partanen, Ari/0000-0003-1985-149X; Mikhail, Andrew/0000-0001-9206-5765
FU Center for Interventional Oncology in the Intramural Research Program of
the National Institutes of Health (NIH); NIH [Z1A CL040015-06]
FX This work was supported by the Center for Interventional Oncology in the
Intramural Research Program of the National Institutes of Health (NIH).
NIH and Celsion Corp. have a Cooperative Research and Development
Agreement (CRADA). NIH and Philips Healthcare have a CRADA supported by
NIH Grant # Z1A CL040015-06. Dr A. Partanen is a paid employee of
Philips Healthcare. The content of this article does not necessarily
reflect the views or policies of the Department of Health and Human
Services, nor does mention of trade names, commercial products, or
organizations imply endorsement by the US Government.
NR 81
TC 2
Z9 2
U1 4
U2 19
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 1064-9689
EI 1557-9786
J9 MAGN RESON IMAGING C
JI Magn. Reson. Imaging Clin. N. Am.
PD NOV
PY 2015
VL 23
IS 4
BP 643
EP +
DI 10.1016/j.mric.2015.05.012
PG 15
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA CX0HN
UT WOS:000365377600014
PM 26499281
ER
PT J
AU Campbell-Washburn, AE
Faranesh, AZ
Lederman, RJ
Hansen, MS
AF Campbell-Washburn, Adrienne E.
Faranesh, Anthony Z.
Lederman, Robert J.
Hansen, Michael S.
TI Magnetic Resonance Sequences and Rapid Acquisition for MR-Guided
Interventions
SO MAGNETIC RESONANCE IMAGING CLINICS OF NORTH AMERICA
LA English
DT Article
DE Real-time MR imaging; MR image reconstruction; Parallel imaging;
Non-Cartesian imaging
ID STATE FREE PRECESSION; COMMODITY GRAPHICS HARDWARE; PASSIVE CATHETER
TRACKING; PLANAR IMAGING EPI; REAL-TIME MRI; PROJECTION RECONSTRUCTION;
TEMPORAL RESOLUTION; SPIRAL TRAJECTORIES; COIL SELECTION; GRAPPA
AB Interventional Magnetic resonance (MR) uses rapid imaging to guide diagnostic and therapeutic procedures. One of the attractions of MR-guidance is the abundance of inherent contrast mechanisms available. Dynamic procedural guidance with real-time imaging has pushed the limits of MR technology, demanding rapid acquisition and reconstruction paired with interactive control and device visualization. This article reviews the technical aspects of real-time MR sequences that enable MR-guided interventions.
C1 [Campbell-Washburn, Adrienne E.; Faranesh, Anthony Z.; Lederman, Robert J.; Hansen, Michael S.] NHLBI, Cardiovasc & Pulm Branch, Div Intramural Res, NIH, Bethesda, MD 20892 USA.
RP Campbell-Washburn, AE (reprint author), NHLBI, Cardiovasc & Pulm Branch, Div Intramural Res, NIH, 9000 Rockville Pike,Bldg 10,Room B1D416, Bethesda, MD 20892 USA.
EM adrienne.campbell@nih.gov
RI Hansen, Michael/J-5391-2015;
OI Hansen, Michael/0000-0002-8087-8731; lederman,
robert/0000-0003-1202-6673
FU National Heart, Lung, and Blood Institute Division of Intramural
Research [Z01-HL006039, Z01-HL005062]
FX The authors disclose that this work was supported by the National Heart,
Lung, and Blood Institute Division of Intramural Research (Z01-HL006039,
Z01-HL005062). The National Heart, Lung, and Blood Institute and Siemens
Medical Systems have a Cooperative Research and Development Agreement
(CRADA).
NR 85
TC 0
Z9 0
U1 1
U2 8
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 1064-9689
EI 1557-9786
J9 MAGN RESON IMAGING C
JI Magn. Reson. Imaging Clin. N. Am.
PD NOV
PY 2015
VL 23
IS 4
BP 669
EP +
DI 10.1016/j.mric.2015.05.006
PG 12
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA CX0HN
UT WOS:000365377600016
PM 26499283
ER
PT J
AU Desler, C
Frederiksen, JH
Angleys, M
Maynard, S
Keijzers, G
Fagerlund, B
Mortensen, EL
Osler, M
Lauritzen, M
Bohr, VA
Rasmussen, LJ
AF Desler, Claus
Frederiksen, Jane H.
Angleys, Maria
Maynard, Scott
Keijzers, Guido
Fagerlund, Birgitte
Mortensen, Erik Lykke
Osler, Merete
Lauritzen, Martin
Bohr, Vilhelm A.
Rasmussen, Lene Juel
TI Increased deoxythymidine triphosphate levels is a feature of relative
cognitive decline
SO MITOCHONDRION
LA English
DT Article
DE Alzheimer's disease; Cognitive decline; Mitochondrial bioenergetics;
Mitochondrial ROS; Deoxyribonucleotide levels
ID ALZHEIMERS-DISEASE; MITOCHONDRIAL DYSFUNCTION; DEMENTIA; POOLS; DNA
AB Mitochondrial bioenergetics, mitochondrial reactive oxygen species (ROS) and cellular levels of nucleotides have been hypothesized as early indicators of Alzheimer's disease (AD). Utilizing relative decline of cognitive ability as a predictor of AD risk, we evaluated the correlation between change of cognitive ability and mitochondrial bioenergetics, ROS and cellular levels of deoxyribonucleotides. Change of cognitive abilities, scored at ages of approximately 20 and 57 was determined for a cohort of 1985 male participants. Mitochondrial bioenergetics, mitochondrial ROS and whole-cell levels of deoxyribonucleotide triphosphates were measured in peripheral blood mononuclear cells (PBMCs) from a total of 103 selected participants displaying the most pronounced relative cognitive decline and relative cognitive improvement. We show that relative cognitive decline is associated with higher PBMC content of deoxythymidine-triphosphate (MP) (20%), but not mitochondrial bioenergetics parameters measured in this study or mitochondrial ROS. Levels of dTTP in PBMCs are indicators of relative cognitive change suggesting a role of deoxyribonucleotides in the etiology of AD. (C) 2015 The Authors. Elsevier B.V. and Mitochondria Research Society.
C1 [Desler, Claus; Frederiksen, Jane H.; Angleys, Maria; Maynard, Scott; Keijzers, Guido; Fagerlund, Birgitte; Mortensen, Erik Lykke; Lauritzen, Martin; Bohr, Vilhelm A.; Rasmussen, Lene Juel] Ctr Hlth Aging, Copenhagen, Denmark.
[Desler, Claus; Frederiksen, Jane H.; Angleys, Maria; Maynard, Scott; Keijzers, Guido; Rasmussen, Lene Juel] Univ Copenhagen, Dept Cellular & Mol Med, DK-1168 Copenhagen, Denmark.
[Fagerlund, Birgitte] Mental Hlth Ctr Glostrup, CNSR, Ctr Clin Intervent & Neuropsychiat Schizophrenia, Lundbeck Fdn, Glostrup, Denmark.
[Mortensen, Erik Lykke; Osler, Merete] Univ Copenhagen, Dept Publ Hlth, DK-1168 Copenhagen, Denmark.
[Osler, Merete] Glostrup Cty Hosp, Res Ctr Prevent & Hlth, Glostrup, Denmark.
[Lauritzen, Martin] Univ Copenhagen, Dept Neurosci & Pharmacol, Copenhagen N, Denmark.
[Lauritzen, Martin] Glostrup Cty Hosp, Dept Clin Neurophysiol, Glostrup, Denmark.
[Bohr, Vilhelm A.] NIA, Lab Mol Gerontol, NIH, Bethesda, MD 20892 USA.
RP Rasmussen, LJ (reprint author), Ctr Hlth Aging, Copenhagen, Denmark.
EM lenera@sund.ku.dk
OI desler, claus/0000-0002-0125-004X; Osler, Merete/0000-0002-6921-220X
FU Nordea-fonden; Danish Council for Independent Research-Natural Sciences
FX This work was supported by a grant from Nordea-fonden (LJR, VB, ELM, ML)
and the The Danish Council for Independent Research-Natural Sciences
(LJR, CD).
NR 16
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 1567-7249
EI 1872-8278
J9 MITOCHONDRION
JI Mitochondrion
PD NOV
PY 2015
VL 25
BP 34
EP 37
DI 10.1016/j.mito.2015.09.002
PG 4
WC Cell Biology; Genetics & Heredity
SC Cell Biology; Genetics & Heredity
GA CX8DW
UT WOS:000365933800005
PM 26408413
ER
PT J
AU Jagoda, EM
Bhattacharyya, S
Kalen, J
Riffle, L
Leeder, A
Histed, S
Williams, M
Wong, KJ
Xu, BY
Szajek, LP
Elbuluk, O
Cecchi, F
Raffensperger, K
Golla, M
Bottaro, DP
Choyke, P
AF Jagoda, Elaine M.
Bhattacharyya, Sibaprasad
Kalen, Joseph
Riffle, Lisa
Leeder, Avrum
Histed, Stephanie
Williams, Mark
Wong, Karen J.
Xu, Biying
Szajek, Lawrence P.
Elbuluk, Osama
Cecchi, Fabiola
Raffensperger, Kristen
Golla, Meghana
Bottaro, Donald P.
Choyke, Peter
TI Imaging the Met Receptor Tyrosine Kinase (Met) and Assessing Tumor
Responses to a Met Tyrosine Kinase Inhibitor in Human Xenograft Mouse
Models with a [Tc-99m] (AH-113018) or Cy 5(**) (AH-112543) Labeled
Peptide
SO MOLECULAR IMAGING
LA English
DT Article
ID CELL LUNG-CANCER; SMALL-MOLECULE INHIBITOR; GROWTH-FACTOR RECEPTOR; GENE
COPY NUMBER; SMALL-ANIMAL PET; SIGNALING PATHWAY; ANTIBODY ONARTUZUMAB;
SELF-DISPLACEMENT; DOWN-REGULATION; IN-VIVO
AB Developing an imaging agent targeting the hepatocyte growth factor receptor protein (Met) status of cancerous lesions would aid in the diagnosis and monitoring of Met-targeted tyrosine kinase inhibitors (TKIs). A peptide targeting Met labeled with [Tc-99m] had high affinity in vitro (K-d = 3.3 nM) and detected relative changes in Met in human cancer cell lines. In vivo [Tc-99m]-Met peptide (AH-113018) was retained in Met-expressing tumors, and high-expressing Met tumors (MKN-45) were easily visualized and quantitated using single-photon emission computed tomography or optical imaging. In further studies, MKN-45 mouse xenografts treated with PHA 665752 (Met TKI) or vehicle were monitored weekly for tumor responses by [Tc-99m]-Met peptide imaging and measurement of tumor volumes. Tumor uptake of [Tc-99m]-Met peptide was significantly decreased as early as 1 week after PHA 665752 treatment, corresponding to decreases in tumor volumes. These results were comparable to Cy5**-Met peptide (AH-112543) fluorescence imaging using the same treatment model. [Tc-99m] or Cy5**-Met peptide tumor uptake was further validated by histologic (necrosis, apoptosis) and immunoassay (total Met, p Met, and plasma shed Met) assessments in imaged and nonimaged cohorts. These data suggest that [Tc-99m] or Cy5**-Met peptide imaging may have clinical diagnostic, prognostic, and therapeutic monitoring applications.
C1 [Jagoda, Elaine M.] NCI, Mol Imaging Program, Bethesda, MD 20892 USA.
Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, ADRD, SAIC Frederick Inc, Frederick, MD USA.
Leidos Biomed Res Inc, Small Anim Imaging Program, NCI, SAIC Frederick Inc, Frederick, MD USA.
NHLBI, Imaging Probe Dev Ctr, NIH, Rockville, MD USA.
NIH, Ctr Clin, PET Dept, Bethesda, MD 20892 USA.
NCI, Urol Oncol Branch, Bethesda, MD 20892 USA.
RP Jagoda, EM (reprint author), NCI, Mol Imaging Program, 10 Ctr Dr,MSC 1088,BLG 10-RM B3B69, Bethesda, MD 20892 USA.
EM ejagoda@mail.nih.gov
FU National Cancer'Institute, National Institutes of Health
[HHSN261200800001E]
FX This project has been funded in whole or in part with federal funds from
the National Cancer'Institute, National Institutes of Health, under
Contract No. HHSN261200800001E. The content of this publication does not
necessarily reflect the views or policies of the Department of Health
and Human Services, nor does mention of trade names, commercial
products, or organizations imply endorsement by the U.S. Government.
NR 51
TC 0
Z9 0
U1 4
U2 9
PU B C DECKER INC
PI HAMILTON
PA 69 JOHN STREET SOUTH, STE 310, HAMILTON, ONTARIO L8N 2B9, CANADA
SN 1535-3508
EI 1536-0121
J9 MOL IMAGING
JI Mol. Imaging
PD NOV
PY 2015
VL 14
BP 499
EP 515
DI 10.2310/7290.2015.00023
PG 17
WC Biochemical Research Methods; Radiology, Nuclear Medicine & Medical
Imaging
SC Biochemistry & Molecular Biology; Radiology, Nuclear Medicine & Medical
Imaging
GA CX3KR
UT WOS:000365598200003
PM 26461980
ER
PT J
AU Statland, JM
Barohn, RJ
Dimachkie, MM
Floeter, MK
Mitsumoto, H
AF Statland, Jeffrey M.
Barohn, Richard J.
Dimachkie, Mazen M.
Floeter, Mary Kay
Mitsumoto, Hiroshi
TI Primary Lateral Sclerosis
SO NEUROLOGIC CLINICS
LA English
DT Article
DE Motor neuron disease; Upper motor neuron disease; Primary lateral
sclerosis; Spastic quadriparesis; Pseudobulbar affect; Neuroimaging
ID MOTOR-NEURON DISEASES; HEREDITARY SPASTIC PARAPLEGIA; CLINICAL-FEATURES;
INVOLVEMENT; DYSFUNCTION; BRAIN; ALS; DISTINGUISH; CORTEX; PLS
AB Primary lateral sclerosis is characterized by insidious onset of progressive upper motor neuron dysfunction in the absence of clinical signs'of lower motor neuron involvement. Patients experience stiffness; decreased balance and coordination; mild weakness; and, if the bulbar region is affected, difficulty speaking and swallowing, and emotional lability. The diagnosis is made based on clinical history, typical examination findings, and diagnostic testing negative for other causes of upper motor neuron dysfunction. Electromyogram is normal, or only shows mild neurogenic findings in a few muscles, not meeting El Escorial criteria. Treatment is largely supportive.
C1 [Statland, Jeffrey M.; Barohn, Richard J.; Dimachkie, Mazen M.] Univ Kansas, Med Ctr, Dept Neurol, Kansas City, KS 66160 USA.
[Floeter, Mary Kay] NINDS, Human Spinal Physiol Unit, Bethesda, MD 20892 USA.
[Mitsumoto, Hiroshi] Columbia Univ, Med Ctr, Dept Neurol, New York, NY 10032 USA.
RP Statland, JM (reprint author), Univ Kansas, Med Ctr, Dept Neurol, 3901 Rainbow Blvd,Mailstop 2012, Kansas City, KS 66160 USA.
EM jstatland@kumc.edu
FU Institutional Clinical and Translational Science Award, NIH/NCATS
[UL1TR000001]; CTSA grant from NCATS [KL2TR000119]; NIH, NINDS [Z01
NS002976]
FX This publication was supported by an Institutional Clinical and
Translational Science Award, NIH/NCATS Grant Number UL1TR000001. J.M.
Statland's work on this project was supported by a CTSA grant from NCATS
awarded to the University of Kansas Medical Center for Frontiers: The
Heartland Institute for Clinical and Translational Research
#KL2TR000119. M.K Floeter's work on this project was supported by the
intramural program of NIH, NINDS, grant # Z01 NS002976. Its contents are
solely the responsibility of the authors and do not necessarily
represent the official views of the NIH.
NR 48
TC 2
Z9 3
U1 2
U2 8
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0733-8619
EI 1557-9875
J9 NEUROL CLIN
JI Neurol. Clin.
PD NOV
PY 2015
VL 33
IS 4
BP 749
EP +
DI 10.1016/j.ncl.2015.07.007
PG 13
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA CX1PA
UT WOS:000365466900004
PM 26515619
ER
PT J
AU Grunseich, C
Fischbeck, KH
AF Grunseich, Christopher
Fischbeck, Kenneth H.
TI Spinal and Bulbar Muscular Atrophy
SO NEUROLOGIC CLINICS
LA English
DT Article
DE Spinal and bulbar muscular atrophy; Kennedy disease; Motor neuron
disease; Androgen receptor
ID TRANSGENIC MOUSE MODEL; AMYOTROPHIC-LATERAL-SCLEROSIS; ANDROGEN
RECEPTOR; KENNEDY-DISEASE; CLINICAL-FEATURES; MEIOTIC STABILITY; CAG
REPEAT; POLYGLUTAMINE; EXPRESSION; AUTOPHAGY
AB Spinal and bulbar muscular atrophy, or Kennedy disease, is a slowly progressive X-linked neuromuscular disease caused by a trinucleotide (CAG) repeat expansion in the androgen receptor gene. Affected males typically develop weakness in their mid-40s as well as evidence of androgen insensitivity with reduced fertility and gynecomastia. Diagnosis is often delayed because of decreased awareness of the disease, although genetic testing allows for direct diagnosis. Therapeutic strategies to block the toxicity of the mutant androgen receptor have been unsuccessful thus far, and evaluation of additional candidate therapies is underway.
C1 [Grunseich, Christopher; Fischbeck, Kenneth H.] Natl Inst Neurol Disorders & Stroke, NIH, Neurogenet Branch, Bethesda, MD 20892 USA.
RP Grunseich, C (reprint author), Natl Inst Neurol Disorders & Stroke, NIH, Neurogenet Branch, 35 Convent Dr, Bethesda, MD 20892 USA.
EM Christopher.grunseich@nih.gov
FU Intramural NIH HHS [Z99 NS999999]
NR 43
TC 0
Z9 0
U1 0
U2 4
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0733-8619
EI 1557-9875
J9 NEUROL CLIN
JI Neurol. Clin.
PD NOV
PY 2015
VL 33
IS 4
BP 847
EP +
DI 10.1016/j.ncl.2015.07.002
PG 9
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA CX1PA
UT WOS:000365466900010
PM 26515625
ER
PT J
AU Bailit, JL
Grobman, WA
McGee, P
Reddy, UM
Wapner, RJ
Varner, MW
Thorp, JM
Leveno, KJ
Iams, JD
Tita, ATN
Saade, G
Sorokin, Y
Rouse, DJ
Blackwell, SC
AF Bailit, Jennifer L.
Grobman, William A.
McGee, Paula
Reddy, Uma M.
Wapner, Ronald J.
Varner, Michael W.
Thorp, John M.
Leveno, Kenneth J.
Iams, Jay D.
Tita, Alan T. N.
Saade, George
Sorokin, Yoram
Rouse, Dwight J.
Blackwell, Sean C.
CA Eunice Kennedy Shriver Natl Inst C
TI Does the Presence of a Condition-Specific Obstetric Protocol Lead to
Detectable Improvements in Pregnancy Outcomes? EDITORIAL COMMENT
SO OBSTETRICAL & GYNECOLOGICAL SURVEY
LA English
DT Editorial Material
C1 [Bailit, Jennifer L.] Case Western Reserve Univ, MetroHlth Med Ctr, Dept Obstet & Gynecol, Cleveland, OH 44106 USA.
[Iams, Jay D.] Ohio State Univ, Dept Obstet & Gynecol, Columbus, OH 43210 USA.
[Grobman, William A.] Northwestern Univ, Prentice Womens Hosp, Chicago, IL 60611 USA.
[Wapner, Ronald J.] Columbia Univ, Coll Phys & Surg, New York, NY USA.
[Varner, Michael W.] Univ Utah, Hlth Sci Ctr, Salt Lake City, UT USA.
[Thorp, John M.] Univ N Carolina, Sch Med, Chapel Hill, NC USA.
[Leveno, Kenneth J.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA.
[Saade, George] Univ Texas Med Branch, Galveston, TX 77555 USA.
[Blackwell, Sean C.] Univ Texas Hlth Sci Ctr Houston, Childrens Mem Hermann Hosp, Houston, TX 77030 USA.
[Tita, Alan T. N.] Univ Alabama Birmingham, Sch Med, Birmingham, AL USA.
[Sorokin, Yoram] Wayne State Univ, Sch Med, Detroit, MI USA.
[Rouse, Dwight J.] Brown Univ, Alpert Med Sch, Providence, RI 02912 USA.
[McGee, Paula] George Washington Univ, Ctr Biostat, Washington, DC USA.
[Reddy, Uma M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
RP Bailit, JL (reprint author), Case Western Reserve Univ, MetroHlth Med Ctr, Dept Obstet & Gynecol, Cleveland, OH 44106 USA.
NR 4
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0029-7828
EI 1533-9866
J9 OBSTET GYNECOL SURV
JI Obstet. Gynecol. Surv.
PD NOV
PY 2015
VL 70
IS 11
BP 679
EP 680
DI 10.1097/01.ogx.0000473082.76430.62
PG 2
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA CW9AE
UT WOS:000365289900004
ER
PT J
AU Bayefsky, MJ
Saylor, KW
Berkman, BE
AF Bayefsky, Michele J.
Saylor, Katherine W.
Berkman, Benjamin E.
TI Parental Consent for the Use of Residual Newborn Screening Bloodspots:
Respecting Individual Liberty vs Ensuring Public Health EDITORIAL
COMMENT
SO OBSTETRICAL & GYNECOLOGICAL SURVEY
LA English
DT Editorial Material
C1 [Bayefsky, Michele J.; Berkman, Benjamin E.] NIH, Ctr Clin, Dept Bioeth, Bethesda, MD 20892 USA.
[Saylor, Katherine W.] NHGRI, Div Policy Commun & Educ, NIH, Bethesda, MD 20892 USA.
[Berkman, Benjamin E.] NHGRI, Bioeth Core, NIH, Bethesda, MD 20892 USA.
RP Bayefsky, MJ (reprint author), NIH, Ctr Clin, Dept Bioeth, Bethesda, MD 20892 USA.
NR 3
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0029-7828
EI 1533-9866
J9 OBSTET GYNECOL SURV
JI Obstet. Gynecol. Surv.
PD NOV
PY 2015
VL 70
IS 11
BP 686
EP 688
DI 10.1097/01.ogx.0000473446.49463.5b
PG 3
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA CW9AE
UT WOS:000365289900008
ER
PT J
AU Nussinov, R
Tsai, CJ
AF Nussinov, Ruth
Tsai, Chung-Jung
TI Tandem Domains with Tuned Interactions Are a Powerful Biological Design
Principle
SO PLOS BIOLOGY
LA English
DT Editorial Material
AB Allosteric effects of mutations, ligand binding, or post-translational modifications on protein function occur through changes to the protein's shape, or conformation. In a cell, there are many copies of the same protein, all experiencing these perturbations in a dynamic fashion and fluctuating through different conformations and activity states. According to the "conformational selection and population shift" theory, ligand binding selects a particular conformation. This perturbs the ensemble and induces a population shift. In a new PLOS Biology paper, Melacini and colleagues describe a novel model of protein regulation, the "Double-Conformational Selection Model", which demonstrates how two tandem ligand-binding domains interact to regulate protein function. Here we explain how tandem domains with tuned interactions but not single domains can provide a blueprint for sensitive activation sensors within a narrow window of ligand concentration, thereby promoting signaling control.
C1 [Nussinov, Ruth; Tsai, Chung-Jung] Leidos Biomed Res Inc, Canc & Inflammat Program, Frederick, MD 21702 USA.
[Nussinov, Ruth; Tsai, Chung-Jung] NCI, Frederick Natl Lab Canc Res, Frederick, MD 21701 USA.
[Nussinov, Ruth] Tel Aviv Univ, Sackler Sch Med, Dept Human Genet & Mol Med, Sackler Inst Mol Med, IL-69978 Tel Aviv, Israel.
RP Nussinov, R (reprint author), Leidos Biomed Res Inc, Canc & Inflammat Program, Frederick, MD 21702 USA.
EM NussinoR@helix.nih.gov
FU Intramural NIH HHS
NR 10
TC 1
Z9 1
U1 8
U2 10
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1545-7885
J9 PLOS BIOL
JI PLoS. Biol.
PD NOV
PY 2015
VL 13
IS 11
AR e1002306
DI 10.1371/journal.pbio.1002306
PG 6
WC Biochemistry & Molecular Biology; Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics
GA CX7RE
UT WOS:000365898900016
PM 26618518
ER
PT J
AU Holzemer, A
Thobakgale, CF
Cruz, CAJ
Garcia-Beltran, WF
Carlson, JM
van Teijlingen, NH
Mann, JK
Jaggernath, M
Kang, SG
Korner, C
Chung, AW
Schafer, JL
Evans, DT
Alter, G
Walker, BD
Goulder, PJ
Carrington, M
Hartmann, P
Pertel, T
Zhou, RH
Ndung'u, T
Altfeld, M
AF Hoelzemer, Angelique
Thobakgale, Christina F.
Cruz, Camilo A. Jimenez
Garcia-Beltran, Wilfredo F.
Carlson, Jonathan M.
van Teijlingen, Nienke H.
Mann, Jaclyn K.
Jaggernath, Manjeetha
Kang, Seung-gu
Koerner, Christian
Chung, Amy W.
Schafer, Jamie L.
Evans, David T.
Alter, Galit
Walker, Bruce D.
Goulder, Philip J.
Carrington, Mary
Hartmann, Pia
Pertel, Thomas
Zhou, Ruhong
Ndung'u, Thumbi
Altfeld, Marcus
TI Selection of an HLA-C*03:04-Restricted HIV-1 p24 Gag Sequence Variant Is
Associated with Viral Escape from KIR2DL3+Natural Killer Cells: Data
from an Observational Cohort in South Africa
SO PLOS MEDICINE
LA English
DT Article
ID IMMUNOGLOBULIN-LIKE RECEPTOR; VIRUS TYPE-1 INFECTION; HLA CLASS-I;
IMMUNE ESCAPE; NK CELLS; PHASE-1 TRIAL; FREE-ENERGY; KIR; RECOGNITION;
PROTEINS
AB Background Viruses can evade immune surveillance, but the underlying mechanisms are insufficiently understood. Here, we sought to understand the mechanisms by which natural killer (NK) cells recognize HIV-1-infected cells and how this virus can evade NK-cell-mediated immune pressure.
Methods and Findings
Two sequence mutations in p24 Gag associated with the presence of specific KIR/HLA combined genotypes were identified in HIV-1 clade C viruses from a large cohort of infected, untreated individuals in South Africa (n = 392), suggesting viral escape from KIR+NK cells through sequence variations within HLA class I-presented epitopes. One sequence polymorphism at position 303 of p24 Gag (TGag303V), selected for in infected individuals with both KIR2DL3 and HLA-C*03:04, enabled significantly better binding of the inhibitory KIR2DL3 receptor to HLA-C*03:04-expressing cells presenting this variant epitope compared to the wild-type epitope (wild-type mean 18.01 +/- 10.45 standard deviation [SD] and variant mean 44.67 +/- 14.42 SD, p = 0.002). Furthermore, activation of primary KIR2DL3+ NK cells from healthy donors in response to HLA-C*03:04+ target cells presenting the variant epitope was significantly reduced in comparison to cells presenting the wild-type sequence (wild-type mean 0.78 +/- .07 standard error of the mean [SEM] and variant mean 0.63 +/- 0.07 SEM, p = 0.012). Structural modeling and surface plasmon resonance of KIR/ peptide/HLA interactions in the context of the different viral sequence variants studied supported these results. Future studies will be needed to assess processing and antigen presentation of the investigated HIV-1 epitope in natural infection, and the consequences for viral control.
Conclusions
These data provide novel insights into how viruses can evade NK cell immunity through the selection of mutations in HLA-presented epitopes that enhance binding to inhibitory NK cell receptors. Better understanding of the mechanisms by which HIV-1 evades NK-cell-mediated immune pressure and the functional validation of a structural modeling approach will facilitate the development of novel targeted immune interventions to harness the antiviral activities of NK
C1 [Hoelzemer, Angelique; Thobakgale, Christina F.; Garcia-Beltran, Wilfredo F.; Koerner, Christian; Chung, Amy W.; Alter, Galit; Walker, Bruce D.; Carrington, Mary; Ndung'u, Thumbi; Altfeld, Marcus] MIT & Harvard, Ragon Inst MGH, Cambridge, MA 02139 USA.
[Hoelzemer, Angelique; Altfeld, Marcus] Heinrich Pette Inst, Leibniz Inst Expt Virol, Hamburg, Germany.
[Hoelzemer, Angelique] Univ Med Ctr Hamburg Eppendorf, Dept Internal Med 1, Hamburg, Germany.
[Thobakgale, Christina F.; Mann, Jaclyn K.; Jaggernath, Manjeetha; Ndung'u, Thumbi] Univ KwaZulu Natal, Nelson R Mandela Sch Med, KwaZulu Natal Res Inst TB & HIV, HIV Pathogenesis Programme,Doris Duke Med Res Ins, Durban, South Africa.
[Cruz, Camilo A. Jimenez; Kang, Seung-gu; Zhou, Ruhong] IBM Thomas J Watson Res Ctr, Computat Biol Ctr, Yorktown Hts, NY USA.
[Carlson, Jonathan M.] Microsoft Res, Los Angeles, CA USA.
[van Teijlingen, Nienke H.] Univ Amsterdam, Acad Med Ctr, Expt Immunol, NL-1105 AZ Amsterdam, Netherlands.
[Schafer, Jamie L.; Evans, David T.] Harvard Univ, Sch Med, Dept Microbiol & Immunobiol, Boston, MA USA.
[Schafer, Jamie L.; Evans, David T.] New England Primate Res Ctr, Div Microbiol, Southborough, MA USA.
[Evans, David T.] Univ Wisconsin, Dept Pathol & Lab Med, Madison, WI USA.
[Goulder, Philip J.] Univ Oxford, Dept Paediat, Oxford, England.
[Carrington, Mary] Frederick Natl Lab Canc Res, Leidos Biomed Res, Expt Immunol Lab, Canc & Inflammat Program, Frederick, MD USA.
[Hartmann, Pia] Univ Cologne, Div Infect Dis, Dept Internal Med 1, D-50931 Cologne, Germany.
[Hartmann, Pia; Ndung'u, Thumbi] Univ Cologne, Inst Med Microbiol Immunol & Hyg, D-50931 Cologne, Germany.
[Pertel, Thomas] Brigham & Womens Hosp, Ctr Neurol Dis, Boston, MA 02115 USA.
[Pertel, Thomas] Harvard Univ, Sch Med, Boston, MA USA.
[Ndung'u, Thumbi] Max Planck Inst Infect Biol, Berlin, Germany.
[Ndung'u, Thumbi] Univ KwaZulu Natal, KwaZulu Natal Res Inst TB & HIV, Nelson R Mandela Sch Med, Durban, South Africa.
RP Holzemer, A (reprint author), MIT & Harvard, Ragon Inst MGH, Cambridge, MA 02139 USA.
EM marcus.altfeld@hpi.uni-hamburg.de
OI Chung, Amy/0000-0003-0020-9704; Korner, Christian/0000-0002-3431-7319
FU Ragon Institute of MGH, MIT and Harvard; Heinrich Pette Institute -
Leibniz Institute for Experimental Virology; NIH [R01 AI066031, P30
AI060354, R01 AI095098, ROI-AI067073, NOI-AI-15422]; Frederick National
Laboratory for Cancer Research [HHSN261200800001E]; Intramural Research
Program of the NIH; Harvard University Center for AIDS Research (CFAR);
NIH Co-Funding and Participating Institutes and Centres: NIAID; NIH
Co-Funding and Participating Institutes and Centres: NCI; NIH Co-Funding
and Participating Institutes and Centres: NICHD; NIH Co-Funding and
Participating Institutes and Centres: NHLBI; NIH Co-Funding and
Participating Institutes and Centres: NIDA; NIH Co-Funding and
Participating Institutes and Centres: NIMH; NIH Co-Funding and
Participating Institutes and Centres: NIA; NIH Co-Funding and
Participating Institutes and Centres: NCCAM; NIH Co-Funding and
Participating Institutes and Centres: FIC; NIH Co-Funding and
Participating Institutes and Centres: OAR; German Academic Exchange
(DAAD); Koeln Fortune Program; Wellcome Trust [102468/Z/13/Z]; National
Research Foundation; Victor Daitz Foundation; Howard Hughes Medical
Institute; Federal Ministry of Education and Research [01KI1017]; DZIF
(German Center for Infection Research)
FX The work was supported by the Ragon Institute of MGH, MIT and Harvard
(http://www.ragoninstitute.org/index.html), The Heinrich Pette Institute
- Leibniz Institute for Experimental Virology
(http://www.hpi-hamburg.de/en/), and the NIH (http://www.nih.gov/) (R01
AI066031). This project has partly been funded with federal funds from
the Frederick National Laboratory for Cancer Research
(http://web.ncifcrf.gov/, contract No. HHSN261200800001E), the
Intramural Research Program of the NIH (Frederick National Lab, Center
for Cancer Research), and Harvard University Center for AIDS Research
(CFAR) (http://cfar.globalhealth.harvar-d.edu/icb/icb.do). CFAR is an
NIH-funded program (P30 AI060354), which is supported by the following
NIH Co-Funding and Participating Institutes and Centres: NIAID, NCI,
NICHD, NHLBI, NIDA, NIMH, NIA, NCCAM, FIC, and OAR. AH was supported by
a German Academic Exchange (DAAD) scholarship (www.daad.de) and the
Koeln Fortune Program
(http://www.medfak.uni-koeln.de/index.php?id=195&L=0). CT was supported
by the Wellcome Trust (102468/Z/13/Z). DTE was supported by NIH R01
AI095098. JM was supported by a scholarship from the National Research
Foundation. TN holds the South African Research Chair in Systems Biology
of HIV/AIDS and is further supported by the Victor Daitz Foundation and
an International Early Career Scientist award from the Howard Hughes
Medical Institute. The Sinikithemba cohort was funded by the NIH (Grant
ROI-AI067073 Contract NOI-AI-15422). PH is funded by the Federal
Ministry of Education and Research grant 01KI1017 and supported by DZIF
(German Center for Infection Research), www.dzif.de. JMC is an employee
of Microsoft Corp; the employer was not involved in the research. The
authors have no conflicting financial interests. The content of this
publication does not necessarily reflect the views or policies of the
Department of Health and Human Services, nor does mention of trade
names, commercial products, or organizations imply endorsement by the
U.S. Government. The funders had no role in study design, data
collection and analysis, decision to publish, or preparation of the
manuscript.
NR 68
TC 10
Z9 10
U1 0
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 NOV
PY 2015
VL 12
IS 11
AR e1001900
DI 10.1371/journal.pmed.1001900
PG 25
WC Medicine, General & Internal
SC General & Internal Medicine
GA CX7UZ
UT WOS:000365909700004
PM 26575988
ER
PT J
AU Dynlacht, JR
Zeman, EM
Held, KD
Deye, J
Vikram, B
Joiner, MC
AF Dynlacht, Joseph R.
Zeman, Elaine M.
Held, Kathryn D.
Deye, James
Vikram, Bhadrasain
Joiner, Michael C.
TI Education and Training Needs in the Radiation Sciences: Problems and
Potential Solutions
SO RADIATION RESEARCH
LA English
DT Article
ID FUKUSHIMA RADIOLOGICAL EMERGENCY; ONCOLOGY RESIDENTS; AMERICAN SOCIETY;
RADIOBIOLOGY; CONSENSUS; DOSIMETRY; FUTURE
AB This article provides a summary of presentations focused on critical education and training issues in radiation oncology, radiobiology and medical physics from a workshop conducted as part of the 60th Annual Meeting of the Radiation Research Society held in Las Vegas, NV (September 21-24, 2014). Also included in this synopsis are pertinent comments and concerns raised by audience members, as well as recommendations for addressing ongoing and future challenges. (C) 2015 by Radiation Research Society
C1 [Dynlacht, Joseph R.] Indiana Univ Sch Med, Dept Radiat Oncol, Indianapolis, IN 46202 USA.
[Zeman, Elaine M.] Univ N Carolina, Dept Radiat Oncol, Sch Med, Chapel Hill, NC 27599 USA.
[Held, Kathryn D.] Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA.
[Held, Kathryn D.] Harvard Univ, Sch Med, Boston, MA 02114 USA.
[Deye, James] NCI, Div Canc Treatment & Diag, Radiat Res Program, Bethesda, MD 20892 USA.
[Vikram, Bhadrasain] NCI, Clin Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Joiner, Michael C.] Wayne State Univ, Sch Med, Dept Oncol, Detroit, MI 48201 USA.
RP Dynlacht, JR (reprint author), Indiana Univ, Dept Radiat Oncol, Indiana Canc Pavil,RT041,535 Barnhill Dr, Indianapolis, IN 46202 USA.
EM jdynlach@iupui.edu
FU National Cancer Institute's Center for Cancer Training [R25CA171971]
FX Dr. Michael Joiner and the "Integrated course in Biology and Physics of
Radiation Oncology" were supported by a grant from the National Cancer
Institute's Center for Cancer Training (award no. R25CA171971).
NR 19
TC 4
Z9 4
U1 0
U2 1
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 NOV
PY 2015
VL 184
IS 5
BP 449
EP 455
DI 10.1667/RR14199.1
PG 7
WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging
SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology,
Nuclear Medicine & Medical Imaging
GA CX6HB
UT WOS:000365800700001
PM 26479274
ER
PT J
AU Thomason, ME
Marusak, HA
Tocco, MA
Vila, AM
McGarragle, O
Rosenberg, DR
AF Thomason, Moriah E.
Marusak, Hilary A.
Tocco, Maria A.
Vila, Angela M.
McGarragle, Olivia
Rosenberg, David R.
TI Altered amygdala connectivity in urban youth exposed to trauma
SO SOCIAL COGNITIVE AND AFFECTIVE NEUROSCIENCE
LA English
DT Article
DE adolescent; child; maltreatment; resting-state; urban
ID POSTTRAUMATIC-STRESS-DISORDER; GENERALIZED ANXIETY DISORDER; NATIONAL
COMORBIDITY SURVEY; INTRINSIC FUNCTIONAL CONNECTIVITY; ADVERSE CHILDHOOD
EXPERIENCES; EARLY-LIFE STRESS; MALTREATED CHILDREN; PREFRONTAL CORTEX;
INTERNALIZING SYMPTOMS; HOUSEHOLD DYSFUNCTION
AB Early life trauma exposure represents a potent risk factor for the development of mental illnesses such as anxiety, depression and post-traumatic stress disorder. Moreover, deleterious consequences of trauma are exacerbated in youth living in impoverished, urban environments. A priori probability maps were used to examine resting-state functional connectivity (FC) of the amygdala in 21 trauma-exposed, and 21 age-and sex-matched urban children and adolescents (youth) without histories of trauma. Intrinsic FC analyses focused on amygdala-medial prefrontal circuitry, a key emotion regulatory pathway in the brain. We discovered reduced negative amygdala-subgenual cingulate connectivity in trauma-exposed youth. Differences between groups were also identified in anterior insula and dorsal anterior cingulate to amygdala connectivity. Overall, results suggest a model in which urban-dwelling trauma-exposed youth lack negative prefrontal to amygdala connectivity that may be critical for regulation of emotional responses. Functional changes in amygdala circuitry might reflect the biological embedding of stress reactivity in early life and mediate enhanced vulnerability to stress-related psychopathology.
C1 [Thomason, Moriah E.; Marusak, Hilary A.; Vila, Angela M.] Wayne State Univ, Merrill Palmer Skillman Inst Child & Family Dev, Detroit, MI 48202 USA.
[Thomason, Moriah E.] Wayne State Univ, Dept Pediat, Sch Med, Detroit, MI 48202 USA.
[Thomason, Moriah E.] NICHD, Perinatol Res Branch, DHHS, NIH, Bethesda, MD USA.
[Marusak, Hilary A.; McGarragle, Olivia; Rosenberg, David R.] Wayne State Univ, Sch Med, Dept Psychiat & Behav Neurosci, Detroit, MI 48202 USA.
[Tocco, Maria A.] Wayne State Univ, Sch Med, Detroit, MI 48202 USA.
RP Thomason, ME (reprint author), Merrill Palmer Skillman Inst, 71 E Ferry St, Detroit, MI 48202 USA.
EM moriah@wayne.edu
FU Merrill Palmer Skillman Institute; Department of Pediatrics, WSU School
of Medicine; National Alliance for Research on Schizophrenia and
Depression (NARSAD); Lycaki-Young Funds; State of Michigan; Detroit
Wayne Mental Health Authority; [R01MH59299]; [R01HD075806]
FX This project was supported in part by the Merrill Palmer Skillman
Institute and the Department of Pediatrics, WSU School of Medicine and
by a National Alliance for Research on Schizophrenia and Depression
(NARSAD) Young Investigator Award (M.E.T.). Further support comes from
Lycaki-Young Funds, State of Michigan, Detroit Wayne Mental Health
Authority, and R01MH59299 (D.R.R.) and R01HD075806 (M.E.T). The authors
would like to thank Pavan K. Jella, for his assistance in neuroimaging
data acquisition; Rita Elias, Melissa Youmans, Mallory Gardner, Timothy
Lozon and Ali Daher for assistance in participant recruitment, scanning
and conducting structured behavioral interviews; Matthew Carroll for
consultation on statistical analyses and are grateful to those families
who volunteered their time to participate in this study.
NR 83
TC 8
Z9 8
U1 5
U2 17
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1749-5016
EI 1749-5024
J9 SOC COGN AFFECT NEUR
JI Soc. Cogn. Affect. Neurosci.
PD NOV
PY 2015
VL 10
IS 11
BP 1460
EP 1468
DI 10.1093/scan/nsv030
PG 9
WC Neurosciences; Psychology; Psychology, Experimental
SC Neurosciences & Neurology; Psychology
GA CX2RR
UT WOS:000365544900003
PM 25836993
ER
PT J
AU Young, KD
Bellgowan, PSF
Bodurka, J
Drevets, WC
AF Young, Kymberly D.
Bellgowan, Patrick S. F.
Bodurka, Jerzy
Drevets, Wayne C.
TI Autobiographical deficits correlate with gray matter volume in depressed
and high risk participants
SO SOCIAL COGNITIVE AND AFFECTIVE NEUROSCIENCE
LA English
DT Article
DE depression; gray matter volume; hippocampus; autobiographical memory;
familial risk; precuneus
ID BRAINS DEFAULT NETWORK; MEMORY SPECIFICITY; SEX-DIFFERENCES; RETRIEVAL;
DISORDER; METAANALYSIS; RELEVANCE; ANATOMY; RECALL; MOOD
AB Autobiographical memory (AM) overgenerality is a consistent neuropsychological feature of major depressive disorder (MDD) and is present in individuals at high-familial risk (HR) of developing MDD. Structural changes have been found in brain regions implicated in AM recall in MDDs and HRs. However, the relationship between selective regional gray matter volume (GMV) differences and AM recall deficits has not been examined. We examined this relationship in 27 HR, 43 unmedicated MDD and 47 low-risk healthy control participants as they completed an AM task during functional magnetic resonance imaging. FreeSurfer was used for automated anatomical image processing and volumetric quantification. Anatomical regions of interest for GMV analysis were selected based on regions most commonly activated in controls as they recall specific AMs according to a recent meta-analysis. Pearson correlations were calculated among volumetric and AM recall data. In HRs and MDDs, left hippocampal volume correlated positively with specific (HRs r = 0.42; MDDs r = 0.60) and inversely with categorical AM recall (HRs r = -0.51; MDDs r = -0.35). In MDDs, left precuneus volume also correlated positively with specific (r = 0.49) and inversely with categorical (r = -0.35) AM recall. Our results suggest selective GMV alterations within the AM network may contribute to AM impairments observed in both HR and MDD individuals.
C1 [Young, Kymberly D.; Bodurka, Jerzy; Drevets, Wayne C.] Laureate Inst Brain Res, Tulsa, OK 74136 USA.
[Bellgowan, Patrick S. F.] NINDS, NIH, Bethesda, MD 20892 USA.
[Bodurka, Jerzy] Univ Oklahoma, Norman, OK 73019 USA.
[Drevets, Wayne C.] Johnson & Johnson Inc, Janssen Pharmaceut, Titusville, NJ USA.
RP Young, KD (reprint author), Laureate Inst Brain Res, 6655 South Yale Ave, Tulsa, OK 74136 USA.
EM kyoung@laureateinstitute.org
OI Young, Kymberly/0000-0001-5133-2142
FU Laureate Institute for Brain Research; William K. Warren Foundation
FX This research was supported by the Laureate Institute for Brain Research
and The William K. Warren Foundation. The funders had no influence on
the design or conduct of the study, collection, management, analyses or
interpretation of the data, or in the preparation, review or approval of
the manuscript.
NR 37
TC 1
Z9 3
U1 1
U2 4
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1749-5016
EI 1749-5024
J9 SOC COGN AFFECT NEUR
JI Soc. Cogn. Affect. Neurosci.
PD NOV
PY 2015
VL 10
IS 11
BP 1588
EP 1595
DI 10.1093/scan/nsv047
PG 8
WC Neurosciences; Psychology; Psychology, Experimental
SC Neurosciences & Neurology; Psychology
GA CX2RR
UT WOS:000365544900016
PM 25925269
ER
PT J
AU Judson, RS
Magpantay, FM
Chickarmane, V
Haskell, C
Tania, N
Taylor, J
Xia, MH
Huang, RL
Rotroff, DM
Filer, DL
Houck, KA
Martin, MT
Sipes, N
Richard, AM
Mansouri, K
Setzer, RW
Knudsen, TB
Crofton, KM
Thomas, RS
AF Judson, Richard S.
Magpantay, Felicia Maria
Chickarmane, Vijay
Haskell, Cymra
Tania, Nessy
Taylor, Jean
Xia, Menghang
Huang, Ruili
Rotroff, Daniel M.
Filer, Dayne L.
Houck, Keith A.
Martin, Matthew T.
Sipes, Nisha
Richard, Ann M.
Mansouri, Kamel
Setzer, R. Woodrow
Knudsen, Thomas B.
Crofton, Kevin M.
Thomas, Russell S.
TI Integrated Model of Chemical Perturbations of a Biological Pathway Using
18 In Vitro High-Throughput Screening Assays for the Estrogen Receptor
SO TOXICOLOGICAL SCIENCES
LA English
DT Article
DE estrogen receptor; EDSP; high-throughput screening; In vitro;
prioritization; biological modeling
ID EPAS TOXCAST PROGRAM; ENVIRONMENTAL CHEMICALS; MOLECULAR-MECHANISMS;
SELECTIVE LIGANDS; BREAST-CANCER; TOXICITY; EXPOSURE; PRIORITIZATION;
IDENTIFICATION; TRANSCRIPTION
AB We demonstrate a computational network model that integrates 18 in vitro, high-throughput screening assays measuring estrogen receptor (ER) binding, dimerization, chromatin binding, transcriptional activation, and ER-dependent cell proliferation. The network model uses activity patterns across the in vitro assays to predict whether a chemical is an ER agonist or antagonist, or is otherwise influencing the assays through a manner dependent on the physics and chemistry of the technology platform ("assay interference"). The method is applied to a library of 1812 commercial and environmental chemicals, including 45 ER positive and negative reference chemicals. Among the reference chemicals, the network model correctly identified the agonists and antagonists with the exception of very weak compounds whose activity was outside the concentration range tested. The model agonist score also correlated with the expected potency class of the active reference chemicals. Of the 1812 chemicals evaluated, 111 (6.1%) were predicted to be strongly ER active in agonist or antagonist mode. This dataset and model were also used to begin a systematic investigation of assay interference. The most prominent cause of false-positive activity (activity in an assay that is likely not due to interaction of the chemical with ER) is cytotoxicity. The model provides the ability to prioritize a large set of important environmental chemicals with human exposure potential for additional in vivo endocrine testing. Finally, this model is generalizable to any molecular pathway for which there are multiple upstream and downstream assays available.
C1 [Judson, Richard S.; Houck, Keith A.; Martin, Matthew T.; Richard, Ann M.; Setzer, R. Woodrow; Knudsen, Thomas B.; Crofton, Kevin M.; Thomas, Russell S.] US EPA, Res Triangle Pk, NC 27711 USA.
[Magpantay, Felicia Maria] Univ Manitoba, Dept Math, Winnipeg, MB R3T 2N2, Canada.
[Chickarmane, Vijay] CALTECH, Div Biol, Pasadena, CA 91125 USA.
[Haskell, Cymra] Univ So Calif, Dept Math, Los Angeles, CA 90089 USA.
[Tania, Nessy] Smith Coll, Dept Math, Northampton, MA 01063 USA.
[Taylor, Jean] NYU, Courant Inst, New York, NY 10012 USA.
[Xia, Menghang; Huang, Ruili] NIH, Chem Genom Ctr, Natl Ctr Adv Translat Sci, Rockville, MD 20892 USA.
[Rotroff, Daniel M.] N Carolina State Univ, Dept Stat, Raleigh, NC 27607 USA.
[Rotroff, Daniel M.] N Carolina State Univ, Bioinformat Res Ctr, Raleigh, NC 27607 USA.
[Filer, Dayne L.; Mansouri, Kamel] US EPA, ORISE, Res Triangle Pk, NC 27711 USA.
[Sipes, Nisha] NIH, Natl Toxicol Program, Res Triangle Pk, NC 27711 USA.
RP Judson, RS (reprint author), US EPA, Res Triangle Pk, NC 27711 USA.
EM judson.richard@epa.gov
RI Crofton, Kevin/J-4798-2015;
OI Crofton, Kevin/0000-0003-1749-9971; Mansouri, Kamel/0000-0002-6426-8036
FU American Institute of Mathematics; National Science Foundation; U.S. EPA
FX The authors gratefully acknowledge the American Institute of Mathematics
and National Science Foundation for support of this research through the
"Modeling Problems Related to Our Environment" workshop held January
14-18, 2013 in Palo Alto, California. All other funding was provided by
the U.S. EPA.
NR 47
TC 24
Z9 24
U1 7
U2 24
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 NOV
PY 2015
VL 148
IS 1
BP 137
EP 154
DI 10.1093/toxsci/kfv168
PG 18
WC Toxicology
SC Toxicology
GA CX2SU
UT WOS:000365547900013
PM 26272952
ER
PT J
AU Bao, QY
Hipp, M
Hugo, A
Lei, J
Liu, Y
Kehl, T
Hechler, T
Lochelt, M
AF Bao, Qiuying
Hipp, Michaela
Hugo, Annette
Lei, Janet
Liu, Yang
Kehl, Timo
Hechler, Torsten
Loechelt, Martin
TI In Vitro Evolution of Bovine Foamy Virus Variants with Enhanced
Cell-Free Virus Titers and Transmission
SO VIRUSES-BASEL
LA English
DT Article
DE bovine foamy virus; retrovirus; particle release; virus budding; Gag
myristoylation; virus transmission
ID TERMINAL GAG DOMAIN; ENV LEADER PROTEIN; SYNCYTIAL VIRUS; SPREAD;
INFECTIVITY; RNA; MYRISTOYLATION; MORPHOGENESIS; REQUIREMENTS;
SPUMAVIRUS
AB Virus transmission is essential for spreading viral infections and is a highly coordinated process which occurs by cell-free transmission or cell-cell contact. The transmission of Bovine Foamy Virus (BFV) is highly cell-associated, with undetectable cell-free transmission. However, BFV particle budding can be induced by overexpression of wild-type (wt) BFV Gag and Env or artificial retargeting of Gag to the plasma membrane via myristoylation membrane targeting signals, closely resembling observations in other foamy viruses. Thus, the particle release machinery of wt BFV appears to be an excellent model system to study viral adaption to cell-free transmission by in vitro selection and evolution. Using selection for BFV variants with high cell-free infectivity in bovine and non-bovine cells, infectivity dramatically increased from almost no infectious units to about 10(5)-10(6) FFU (fluorescent focus forming units)/mL in both cell types. Importantly, the selected BFV variants with high titer (HT) cell-free infectivity could still transmit via cell-cell contacts and were neutralized by serum from naturally infected cows. These selected HT-BFV variants will shed light into virus transmission and potential routes of intervention in the spread of viral infections. It will also allow the improvement or development of new promising approaches for antiretroviral therapies.
C1 [Bao, Qiuying; Hipp, Michaela; Hugo, Annette; Lei, Janet; Liu, Yang; Kehl, Timo; Hechler, Torsten; Loechelt, Martin] German Canc Res Ctr, Deutsch Krebsforschungszentrum, DKFZ, Div Molecuar Diagnost Oncogen Infect Res Focus In, D-69120 Heidelberg, Germany.
[Lei, Janet] Univ Oxford, Dept Oncol, Oxford OX3 7DQ, England.
[Liu, Yang] NCI, Dept Viral Recombinat, HIV Dynam & Replicat Program, Ctr Canc Res, Frederick, MD 21702 USA.
[Hechler, Torsten] Heidelberg Pharma GmbH, D-68526 Heidelberg, Germany.
RP Lochelt, M (reprint author), German Canc Res Ctr, Deutsch Krebsforschungszentrum, DKFZ, Div Molecuar Diagnost Oncogen Infect Res Focus In, D-69120 Heidelberg, Germany.
EM q.bao@dkfz.de; m.hipp@dkfz.de; a.hugo@dkfz.de;
janet.lei@oncology.ox.ac.uk; liuy18@nih.gov; t.kehl@dkfz.de;
t.hechler@hdpharma.com; m.loechelt@dkfz.de
OI Lei, Janet/0000-0001-6486-9651
FU China Scholarship Council (CSC)
FX We thank Lutz Gissmann for continuous support, Birgit Hub for electron
microscopy and Juliane Hafermann for critically reading the manuscript
(all Deutsches Krebsforschungszentrum, Heidelberg, Germany), Roland
Riebe (Friedrich Loffler-Institut, Riems, Germany) for the BFV-Riems
isolate and many helpful suggestions and discussions, Magdalena
Materniak and Jacek Kuzmak (National Veterinary Research Institute,
PIWet, Pulawy, Poland) for bovine and hyper-immune sera and Wentao Qiao
(Nankai University, Tianjin, China) for providing the BICL cells. Q.B.
is supported by an international PhD stipend from the China Scholarship
Council (CSC).
NR 51
TC 1
Z9 1
U1 2
U2 2
PU MDPI AG
PI BASEL
PA POSTFACH, CH-4005 BASEL, SWITZERLAND
SN 1999-4915
J9 VIRUSES-BASEL
JI Viruses-Basel
PD NOV
PY 2015
VL 7
IS 11
BP 5855
EP 5874
DI 10.3390/v7112907
PG 20
WC Virology
SC Virology
GA CX4GB
UT WOS:000365656000015
PM 26569290
ER
PT J
AU Shchetinin, AM
Lvov, DK
Deriabin, PG
Botikov, AG
Gitelman, AK
Kuhn, JH
Alkhovsky, SV
AF Shchetinin, Alexey M.
Lvov, Dmitry K.
Deriabin, Petr G.
Botikov, Andrey G.
Gitelman, Asya K.
Kuhn, Jens H.
Alkhovsky, Sergey V.
TI Genetic and Phylogenetic Characterization of Tataguine and Witwatersrand
Viruses and Other Orthobunyaviruses of the Anopheles A, Capim, Guama,
Koongol, Mapputta, Tete, and Turlock Serogroups
SO VIRUSES-BASEL
LA English
DT Article
DE Anopheles A virus; bunyavirus; Capim virus; Guama virus; Koongol virus;
orthobunyavirus; Tataguine virus; Tete virus; Turlock virus;
Witwatersrand virus
ID COMPLEX GENUS PHLEBOVIRUS; TICK-BORNE PHLEBOVIRUSES; FAMILY
BUNYAVIRIDAE; ARBOVIRUS INFECTION; BUNYAMWERA-VIRUS; MOLECULAR
CHARACTERIZATION; ANTIGENIC RELATIONSHIPS; NUCLEOTIDE-SEQUENCE; NORTH
QUEENSLAND; TAXONOMIC STATUS
AB The family Bunyaviridae has more than 530 members that are distributed among five genera or remain to be classified. The genus Orthobunyavirus is the most diverse bunyaviral genus with more than 220 viruses that have been assigned to more than 18 serogroups based on serological cross-reactions and limited molecular-biological characterization. Sequence information for all three orthobunyaviral genome segments is only available for viruses belonging to the Bunyamwera, Bwamba/Pongola, California encephalitis, Gamboa, Group C, Mapputta, Nyando, and Simbu serogroups. Here we present coding-complete sequences for all three genome segments of 15 orthobunyaviruses belonging to the Anopheles A, Capim, Guama, Kongool, Tete, and Turlock serogroups, and of two unclassified bunyaviruses previously not known to be orthobunyaviruses (Tataguine and Witwatersrand viruses). Using those sequence data, we established the most comprehensive phylogeny of the Orthobunyavirus genus to date, now covering 15 serogroups. Our results emphasize the high genetic diversity of orthobunyaviruses and reveal that the presence of the small nonstructural protein (NSs)-encoding open reading frame is not as common in orthobunyavirus genomes as previously thought.
C1 [Shchetinin, Alexey M.; Lvov, Dmitry K.; Deriabin, Petr G.; Botikov, Andrey G.; Gitelman, Asya K.; Alkhovsky, Sergey V.] Minist Hlth Russian Federat, DI Ivanovskii Virol Inst, Gamaleya Fed Res Ctr Epidemiol & Microbiol, Moscow 123098, Russia.
[Kuhn, Jens H.] NIAID, Integrated Res Facil Ft Detrick, NIH, Ft Detrick, MD 21702 USA.
RP Alkhovsky, SV (reprint author), Minist Hlth Russian Federat, DI Ivanovskii Virol Inst, Gamaleya Fed Res Ctr Epidemiol & Microbiol, Moscow 123098, Russia.
EM shchetinin.alexey@yandex.ru; dk_lvov@mail.ru; pg_deryabin@mail.ru;
tessey@mail.ru; gitelman_ak@mail.ru; kuhnjens@mail.nih.gov;
salkh@yandex.ru
FU Russian Foundation for Basic Research (RFBR) [13-04-01749a]; Battelle
Memorial Institute's prime; US National Institute of Allergy and
Infectious Diseases (NIAID) [HHSN272200700016I]
FX The authors thank Laura Bollinger (IRF-Frederick) for critically editing
this paper. This work was funded by the Russian Foundation for Basic
Research (RFBR) according to research project 13-04-01749a. The content
of this publication does not necessarily reflect the views or policies
of the US Department of Health and Human Services, or the institutions
and companies affiliated with the authors. This work was supported in
part through Battelle Memorial Institute's prime contract with the US
National Institute of Allergy and Infectious Diseases (NIAID) under
Contract No. HHSN272200700016I. A subcontractor to Battelle Memorial
Institute who performed this work is: J.H.K., an employee of Tunnell
Government Services, Inc. (Bethesda, MD, USA).
NR 110
TC 4
Z9 4
U1 5
U2 7
PU MDPI AG
PI BASEL
PA ST ALBAN-ANLAGE 66, CH-4052 BASEL, SWITZERLAND
SN 1999-4915
J9 VIRUSES-BASEL
JI Viruses-Basel
PD NOV
PY 2015
VL 7
IS 11
BP 5987
EP 6008
DI 10.3390/v7112918
PG 22
WC Virology
SC Virology
GA CX4GB
UT WOS:000365656000023
PM 26610546
ER
PT J
AU Jha, A
Ahuja, M
Muallem, S
AF Jha, Archana
Ahuja, Malini
Muallem, Shmuel
TI Properties and function of the lysosomal channels TPCs and TRPML1
SO ACTA PHYSIOLOGICA
LA English
DT Meeting Abstract
C1 [Jha, Archana; Ahuja, Malini; Muallem, Shmuel] NIDCR, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1748-1708
EI 1748-1716
J9 ACTA PHYSIOL
JI Acta Physiol.
PD NOV
PY 2015
VL 215
SU 705
SI SI
MA S11-2
BP 43
EP 43
PG 1
WC Physiology
SC Physiology
GA CW1XX
UT WOS:000364786400093
ER
PT J
AU Hansen, M
Smith, MC
Crist, RM
Clogston, JD
McNeil, S
AF Hansen, Matthew
Smith, Mackensie C.
Crist, Rachael M.
Clogston, Jeffrey D.
McNeil, Scott E.
TI Analyzing the influence of PEG molecular weight on the separation of
PEGylated gold nanoparticles by asymmetric-flow field-flow fractionation
SO ANALYTICAL AND BIOANALYTICAL CHEMISTRY
LA English
DT Article
DE Polyethylene glycol; Surface characterization; Asymmetric-flow
field-flow fractionation; Gold nanoparticles; Separation
ID UV-VIS DETECTION; PROTEIN SURFACE INTERACTIONS;
CAPILLARY-ELECTROPHORESIS; POLYETHYLENE OXIDE; GEL-ELECTROPHORESIS;
NANOROD SEPARATION; AU NANOPARTICLES; SIZE; THERAPY; CHROMATOGRAPHY
AB Polyethylene glycol (PEG) is an important tool for increasing the biocompatibility of nanoparticle therapeutics. Understanding how these potential nanomedicines will react after they have been introduced into the bloodstream is a critical component of the preclinical evaluation process. Hence, it is paramount that better methods for separating, characterizing, and analyzing these complex and polydisperse formulations are developed. We present a method for separating nominal 30-nm gold nanoparticles coated with various molecular weight PEG moieties that uses only phosphate-buffered saline as the mobile phase, without the need for stabilizing surfactants. The optimized asymmetric-flow field-flow fractionation technique using in-line multiangle light scattering, dynamic light scattering, refractive index, and UV-vis detectors allowed successful separation and detection of a mixture of nanoparticles coated with 2-, 5-, 10-, and 20-kDa PEG. The particles coated with the larger PEG species (10 and 20 kDa) were eluted at times significantly earlier than predicted by field-flow fractionation theory. This was attributed to a lower-density PEG shell for the higher molecular weight PEGylated nanoparticles, which allows a more fluid PEG surface that can be greater influenced by external forces. Hence, the apparent particle hydrodynamic size may fluctuate significantly depending on the overall density of the stabilizing surface coating when an external force is applied. This has considerable implications for PEGylated nanoparticles intended for in vivo application, as nanoparticle size is important for determining circulation times, accumulation sites, and routes of excretion, and highlights the importance and value of the use of secondary size detectors when one is working with complex samples in asymmetric-flow field-flow fractionation.
C1 [Hansen, Matthew; Smith, Mackensie C.; Crist, Rachael M.; Clogston, Jeffrey D.; McNeil, Scott E.] Frederick Natl Lab Canc Res, Leidos Biomed Res Inc, Canc Res Technol Program, Nanotechnol Characterizat Lab, Frederick, MD 21702 USA.
RP Clogston, JD (reprint author), Frederick Natl Lab Canc Res, Leidos Biomed Res Inc, Canc Res Technol Program, Nanotechnol Characterizat Lab, Frederick, MD 21702 USA.
EM jeffrey.clogston@nih.gov
RI Nanotechnology Characterization Lab, NCL/K-8454-2012; Crist,
Rachael/K-7603-2012
FU National Cancer Institute, National Institutes of Health
[HHSN261200800001E]
FX This project has been funded in whole or in part with federal funds from
the National Cancer Institute, National Institutes of Health, under
contract no. HHSN261200800001E. The content of this publication does not
necessarily reflect the views or policies of the Department of Health
and Human Services, nor does mention of trade names, commercial
products, or organizations imply endorsement by the US Government.
NR 47
TC 3
Z9 3
U1 3
U2 23
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 1618-2642
EI 1618-2650
J9 ANAL BIOANAL CHEM
JI Anal. Bioanal. Chem.
PD NOV
PY 2015
VL 407
IS 29
BP 8661
EP 8672
DI 10.1007/s00216-015-9056-9
PG 12
WC Biochemical Research Methods; Chemistry, Analytical
SC Biochemistry & Molecular Biology; Chemistry
GA CW7HS
UT WOS:000365169500003
PM 26449845
ER
PT J
AU Thomas, A
Giaccone, G
AF Thomas, A.
Giaccone, G.
TI Why has active immunotherapy not worked in lung cancer?
SO ANNALS OF ONCOLOGY
LA English
DT Review
DE active immunotherapy; vaccines; nonsmall-cell lung cancer; immune
checkpoint; tumor-mediated immunosuppression
ID NONSMALL-CELL LUNG; BLP25 LIPOSOME VACCINE; MAJOR HISTOCOMPATIBILITY
COMPLEX; TRANSFORMING-GROWTH-FACTOR; REGULATORY T-CELLS; CLASS-I;
ANTIGEN PRESENTATION; IMMUNE-SYSTEM; PHASE-II; ANTITUMOR IMMUNITY
AB This paper reviews the phase III trial results of antigen-specific immunotherapeutic approaches in nonsmall-cell lung cancer and explores in-depth the potential reasons behind their failure and discuss strategies for the future.Vaccines that rely on active specific stimulation of the host immune system have the potential to trigger durable antitumor responses with minimal toxicity. However, in nonsmall-cell lung cancer (NSCLC), several large phase III trials of vaccines reported within the last year have yielded disappointing results. Compared with placebo, belagenpumatucel-L (an allogenic tumor cell vaccine), tecemotide (a peptide vaccine targeting MUC-1) and melanoma-associated antigen-A3 (a protein-based vaccine) did not improve outcomes in NSCLC. The lack of clinically significant outcomes, despite their ability to prime and expand tumor antigen-specific T cells could at least partly be attributed to the inability of vaccine-induced T-cell responses to overcome the tumoral mechanisms of immune escape which limit the clonal expansion of T cells following vaccination. A number of such mechanisms have been recognized including reduced antigen presentation, antigenic loss, cytokines, immunosuppressive cells and immune checkpoints. Strategies aimed at modulating the immune checkpoints have shown promise and are on the verge of revolutionizing the therapeutic landscape of metastatic NSCLC. Overcoming immune tolerance and improving the activation of antitumor T cells via combinatorial approaches may represent a new and more promising therapeutic application for active immunotherapies in NSCLC.
C1 [Thomas, A.] NCI, Thorac & GI Oncol Branch, Bethesda, MD 20892 USA.
[Giaccone, G.] Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC 20057 USA.
RP Giaccone, G (reprint author), Georgetown Univ, Lombardi Comprehens Canc Ctr, Res Bldg Room W503,3970 Reservoir Rd NW, Washington, DC 20057 USA.
EM gg496@georgetown.edu
RI Giaccone, Giuseppe/E-8297-2017
OI Giaccone, Giuseppe/0000-0002-5023-7562
FU Intramural program, National Cancer Institute, National Institutes of
Health
FX This work was supported by the Intramural program, National Cancer
Institute, National Institutes of Health. No grant numbers apply.
NR 64
TC 12
Z9 12
U1 4
U2 10
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 NOV
PY 2015
VL 26
IS 11
BP 2213
EP 2220
DI 10.1093/annonc/mdv323
PG 8
WC Oncology
SC Oncology
GA CW7DW
UT WOS:000365159200003
PM 26232492
ER
PT J
AU Genkinger, JM
Kitahara, CM
Bernstein, L
de Gonzalez, AB
Brotzman, M
Elena, JW
Giles, GG
Hartge, P
Singh, PN
Stolzenberg-Solomon, RZ
Weiderpass, E
Adami, HO
Anderson, KE
Beane-Freeman, LE
Buring, JE
Fraser, GE
Fuchs, CS
Gapstur, SM
Gaziano, JM
Helzlsouer, KJ
Lacey, JV
Linet, MS
Liu, JJ
Park, Y
Peters, U
Purdue, MP
Robien, K
Schairer, C
Sesso, HD
Visvanathan, K
White, E
Wolk, A
Wolpin, BM
Zeleniuch-Jacquotte, A
Jacobs, EJ
AF Genkinger, J. M.
Kitahara, C. M.
Bernstein, L.
de Gonzalez, A. Berrington
Brotzman, M.
Elena, J. W.
Giles, G. G.
Hartge, P.
Singh, P. N.
Stolzenberg-Solomon, R. Z.
Weiderpass, E.
Adami, H. -O.
Anderson, K. E.
Beane-Freeman, L. E.
Buring, J. E.
Fraser, G. E.
Fuchs, C. S.
Gapstur, S. M.
Gaziano, J. M.
Helzlsouer, K. J.
Lacey, J. V., Jr.
Linet, M. S.
Liu, J. J.
Park, Y.
Peters, U.
Purdue, M. P.
Robien, K.
Schairer, C.
Sesso, H. D.
Visvanathan, K.
White, E.
Wolk, A.
Wolpin, B. M.
Zeleniuch-Jacquotte, A.
Jacobs, E. J.
TI Central adiposity, obesity during early adulthood, and pancreatic cancer
mortality in a pooled analysis of cohort studies
SO ANNALS OF ONCOLOGY
LA English
DT Review
DE central adiposity; BMI; pancreatic cancer; pooled analysis
ID BODY-MASS INDEX; LONGITUDINAL FOLLOW-UP; WAIST CIRCUMFERENCE;
CARDIOVASCULAR-DISEASE; ABDOMINAL ADIPOSITY; INSULIN-RESISTANCE;
PHYSICAL-ACTIVITY; BREAST-CANCER; RISK-FACTORS; HEALTH
AB positively associated with pancreatic cancer. However, little evidence exists regarding the influence of central adiposity, a high BMI during early adulthood, and weight gain after early adulthood on pancreatic cancer risk. Design: We conducted a pooled analysis of individual-level data from 20 prospective cohort studies in the National Cancer Institute BMI and Mortality Cohort Consortium to examine the association of pancreatic cancer mortality with measures of central adiposity ( e. g. waist circumference; n = 647 478; 1947 pancreatic cancer deaths), BMI during early adulthood ( ages 18- 21 years) and BMI change between early adulthood and cohort enrollment, mostly in middle age or later ( n = 1 096 492; 3223 pancreatic cancer deaths). Multivariable hazard ratios ( HRs) and 95% confidence intervals ( CIs) were calculated using Cox proportional hazards regression models. Results: Higher waist-to-hip ratio ( HR = 1.09, 95% CI 1.02- 1.17 per 0.1 increment) and waist circumference ( HR = 1.07, 95% CI 1.00- 1.14 per 10 cm) were associated with increased risk of pancreatic cancer mortality, even when adjusted for BMI at baseline. BMI during early adulthood was associated with increased pancreatic cancer mortality ( HR = 1.18, 95% CI 1.11- 1.25 per 5 kg/ m2), with increased risk observed in both overweight and obese individuals ( compared with BMI of 21.0 to < 23 kg/ m(2), HR = 1.36, 95% CI 1.20- 1.55 for BMI 25.0 < 27.5 kg/ m2, HR = 1.48, 95% CI 1.20- 1.84 for BMI 27.5 to < 30 kg/ m2, HR = 1.43, 95% CI 1.11- 1.85 for BMI = 30 kg/ m2). BMI gain after early adulthood, adjusted for early adult BMI, was less strongly associated with pancreatic cancer mortality ( HR = 1.05, 95% CI 1.01- 1.10 per 5 kg/ m2). Conclusions: Our results support an association between pancreatic cancer mortality and central obesity, independent of BMI, and also suggest that being overweight or obese during early adulthood may be important in influencing pancreatic cancer mortality risk later in life.
C1 [Genkinger, J. M.] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY 10032 USA.
[Genkinger, J. M.] Columbia Univ, Med Ctr, Herbert Irving Comprehens Canc Ctr, New York, NY 10032 USA.
[Kitahara, C. M.; de Gonzalez, A. Berrington; Hartge, P.; Stolzenberg-Solomon, R. Z.; Beane-Freeman, L. E.; Linet, M. S.; Liu, J. J.; Park, Y.; Purdue, M. P.; Schairer, C.] Natl Canc Inst, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD USA.
[Bernstein, L.] City Hope Natl Med Ctr, Div Canc Etiol, Duarte, CA 91010 USA.
[Brotzman, M.] WESTAT Corp, Rockville, MD 20850 USA.
[Elena, J. W.] NCI, Div Canc Control & Populat Sci, NIH, DHHS, Bethesda, MD 20892 USA.
[Giles, G. G.] Univ Melbourne, Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic, Australia.
[Giles, G. G.] Univ Melbourne, Melbourne Sch Populat & Global Hlth, Ctr Biostat & Epidemiol, Melbourne, Vic, Australia.
[Singh, P. N.; Fraser, G. E.] Loma Linda Univ, Sch Med, Dept Epidemiol Biostat & Populat Med, Loma Linda, CA USA.
[Singh, P. N.; Fraser, G. E.] Loma Linda Univ, Ctr Hlth Res, Loma Linda, CA USA.
[Weiderpass, E.] Univ Tromso, Arctic Univ Norway, Fac Hlth Sci, Dept Community Med, Tromso, Norway.
[Weiderpass, E.] Canc Registry Norway, Dept Res, Oslo, Norway.
[Weiderpass, E.; Adami, H. -O.] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
[Weiderpass, E.] Folkhalsan Res Ctr, Genet Epidemiol Grp, Helsinki, Finland.
[Adami, H. -O.; Buring, J. E.; Sesso, H. D.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Anderson, K. E.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA.
[Anderson, K. E.] Univ Minnesota, Masonic Canc Ctr, Minneapolis, MN USA.
[Buring, J. E.; Sesso, H. D.] Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02115 USA.
[Buring, J. E.; Fuchs, C. S.; Sesso, H. D.; Wolpin, B. M.] Harvard Univ, Sch Med, Boston, MA USA.
[Fuchs, C. S.; Wolpin, B. M.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA.
[Fuchs, C. S.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Gapstur, S. M.; Jacobs, E. J.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA.
[Gaziano, J. M.; Sesso, H. D.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Aging, Boston, MA 02115 USA.
[Gaziano, J. M.] VA Boston Healthcare Syst, Massachusetts Vet Epidemiol Res & Informat Ctr, Ctr Geriatr Res Educ & Clin, Boston, MA USA.
[Helzlsouer, K. J.] St Johns Mercy Med Ctr, Prevent & Res Ctr, Baltimore, MD USA.
[Helzlsouer, K. J.; Visvanathan, K.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Park, Y.] Washington Univ, Div Publ Hlth Sci, Sch Med, St Louis, MO 63130 USA.
[Peters, U.; White, E.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Peters, U.; White, E.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Robien, K.] George Washington Univ, Milken Inst Sch Publ Hlth, Dept Exercise & Nutr Sci, Washington, DC USA.
[Visvanathan, K.] Johns Hopkins Sch Med, Sidney Kimmel Canc Ctr, Dept Med Oncol, Baltimore, MD USA.
[Wolk, A.] Karolinska Inst, Inst Environm Med, Div Nutr Epidemiol, S-10401 Stockholm, Sweden.
[Zeleniuch-Jacquotte, A.] NYU, Dept Populat Hlth, New York, NY USA.
[Zeleniuch-Jacquotte, A.] NYU, Perlmutter Canc Ctr, New York, NY USA.
RP Genkinger, JM (reprint author), Columbia Univ, Mailman Sch Publ Hlth, 722 W 168th St,Rm 803, New York, NY 10032 USA.
EM jg3081@columbia.edu
RI Purdue, Mark/C-9228-2016; Weiderpass, Elisabete/M-4029-2016; Beane
Freeman, Laura/C-4468-2015; Kitahara, Cari/R-8267-2016;
OI Purdue, Mark/0000-0003-1177-3108; Weiderpass,
Elisabete/0000-0003-2237-0128; Beane Freeman, Laura/0000-0003-1294-4124;
Robien, Kim/0000-0002-2120-2280; Giles, Graham/0000-0003-4946-9099;
Zeleniuch-Jacquotte, Anne/0000-0001-9350-1303
FU Intramural NIH HHS; NCI NIH HHS [CA105069, CA 016087, CA 34944, CA
40360, CA 77398, CA 97193, CA047988, K05 CA154337, P01 CA055075, P01
CA87969, P30 CA015704, R01 CA 098661, R01 CA105069, R01 CA124908, R01
CA39742, R01 CA49449, R01-CA14703, UM1 CA167552, UM1 CA182913, UM1
CA182934, UM1 CA186107, Z99CA999999]; NHLBI NIH HHS [HL 26490, HL 34595,
HL043851, HL080467, R01- HL26210]; NIA NIH HHS [5U01AG018033, U01
AG18033]; NIEHS NIH HHS [ES 000260, Z01 ES049030-11]; PHS HHS [Z01
P010119]
NR 62
TC 5
Z9 5
U1 1
U2 6
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 NOV
PY 2015
VL 26
IS 11
BP 2257
EP 2266
DI 10.1093/annonc/mdv355
PG 10
WC Oncology
SC Oncology
GA CW7DW
UT WOS:000365159200006
PM 26347100
ER
PT J
AU Cho, HY
Kleeberger, S
AF Cho, Hye-Youn
Kleeberger, Steven R.
TI Association of Nrf2 with airway pathogenesis: lessons learned from
genetic mouse models
SO ARCHIVES OF TOXICOLOGY
LA English
DT Review
DE Nfe2l2; Lung; Knockout mice; Oxidative stress; Antioxidant response
element
ID RESPIRATORY SYNCYTIAL VIRUS; ACUTE LUNG INJURY; TRANSCRIPTION FACTOR
NRF2; EXTRACELLULAR-SUPEROXIDE DISMUTASE; OBSTRUCTIVE PULMONARY-DISEASE;
ANTIOXIDANT RESPONSE ELEMENTS; ERYTHROID 2-RELATED FACTOR-2;
GLUTATHIONE-S-TRANSFERASE; DIESEL EXHAUST PARTICLES; SMOKE-INDUCED
EMPHYSEMA
AB Nrf2 is a key transcription factor for antioxidant response element (ARE)-bearing genes involved in diverse host defense functions including redox balance, cell cycle, immunity, mitochondrial biogenesis, energy metabolism, and carcinogenesis. Nrf2 in the airways is particularly essential as the respiratory system continuously interfaces with environmental stress. Since Nrf2 was determined to be a susceptibility gene for a model of acute lung injury, its protective capacity in the airways has been demonstrated in experimental models of human disorders using Nrf2 mutant mice which were susceptible to supplemental respiratory therapy (e.g., hyperoxia, mechanical ventilation), cigarette smoke, allergens, virus, environmental pollutants, and fibrotic agents compared to wild-type littermates. Recent studies also determined that Nrf2 is indispensable in developmental lung injury. While association studies with genetic NRF2 polymorphisms supported a protective role for murine Nrf2 in oxidative airway diseases, somatic NRF2 mutations enhanced NRF2-ARE responses, and were favorable for lung carcinogenesis and chemoresistance. Bioinformatic tools have elucidated direct Nrf2 targets as well as Nrf2-interacting networks. Moreover, potent Nrf2-ARE agonists protected oxidant-induced lung phenotypes in model systems, suggesting a therapeutic or preventive intervention. Further investigations on Nrf2 should yield greater understanding of its contribution to normal and pathophysiological function in the airways.
C1 [Cho, Hye-Youn; Kleeberger, Steven R.] NIEHS, Immun Inflammat & Dis Lab, NIH, Res Triangle Pk, NC 27709 USA.
RP Cho, HY (reprint author), NIEHS, Immun Inflammat & Dis Lab, NIH, 111 TW Alexander Dr,Bldg 101,MD D-201, Res Triangle Pk, NC 27709 USA.
EM cho2@niehs.nih.gov
FU NIH, National Institute of Environmental Health Sciences, Department of
Health and Human Services
FX This research was supported (in part) by the Intramural Research Program
of the NIH, National Institute of Environmental Health Sciences,
Department of Health and Human Services. The authors thank Drs. Donald
Cook and Michael Fessler for thoughtful comments on the manuscript.
NR 203
TC 4
Z9 4
U1 4
U2 10
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 0340-5761
EI 1432-0738
J9 ARCH TOXICOL
JI Arch. Toxicol.
PD NOV
PY 2015
VL 89
IS 11
BP 1931
EP 1957
DI 10.1007/s00204-015-1557-y
PG 27
WC Toxicology
SC Toxicology
GA CX0WK
UT WOS:000365417800003
PM 26194645
ER
PT J
AU Rother, KI
Sylvetsky, AC
Schiffman, SS
AF Rother, Kristina I.
Sylvetsky, Allison C.
Schiffman, S. S.
TI Non-nutritive sweeteners in breast milk: perspective on potential
implications of recent findings
SO ARCHIVES OF TOXICOLOGY
LA English
DT Letter
ID P-GLYCOPROTEIN; GUT MICROBIOTA; HEALTH; ONTOGENY; EXPRESSION; SUCRALOSE;
OBESITY
C1 [Rother, Kristina I.; Sylvetsky, Allison C.] NIDDK, Sect Pediat Diabet & Metab, NIH, Bethesda, MD 20892 USA.
[Sylvetsky, Allison C.] George Washington Univ, Milken Inst Sch Publ Hlth, Dept Exercise & Nutr Sci, Washington, DC USA.
[Schiffman, S. S.] N Carolina State Univ, Dept Elect & Comp Engn, Raleigh, NC 27695 USA.
RP Rother, KI (reprint author), NIDDK, Sect Pediat Diabet & Metab, NIH, 9000 Rockville Pike,Bldg 10,Room 8C-432A, Bethesda, MD 20892 USA.
EM kristina.rother@nih.gov
FU Intramural NIH HHS [ZIA DK075093-01, ZIA DK075093-02, ZIA DK075093-03]
NR 24
TC 3
Z9 3
U1 2
U2 13
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 0340-5761
EI 1432-0738
J9 ARCH TOXICOL
JI Arch. Toxicol.
PD NOV
PY 2015
VL 89
IS 11
BP 2169
EP 2171
DI 10.1007/s00204-015-1611-9
PG 3
WC Toxicology
SC Toxicology
GA CX0WK
UT WOS:000365417800023
PM 26462668
ER
PT J
AU Makarova, KS
Galperin, MY
Koonin, EV
AF Makarova, Kira S.
Galperin, Michael Y.
Koonin, Eugene V.
TI Comparative genomic analysis of evolutionarily conserved but
functionally uncharacterized membrane proteins in archaea: Prediction of
novel components of secretion, membrane remodeling and glycosylation
systems
SO BIOCHIMIE
LA English
DT Article
DE Archaeal genomes; arCOGs; Membrane proteins; Gene neighborhoods
ID HORIZONTAL GENE-TRANSFER; HALOFERAX-VOLCANII; BACILLUS-SUBTILIS;
N-GLYCOSYLATION; PHOSPHOLIPID BIOSYNTHESIS; STAPHYLOCOCCUS-AUREUS;
ORTHOLOGOUS GENES; CELL-SURFACE; TTT FAMILY; COMPLEX
AB A systematic comparative genomic analysis of all archaeal membrane proteins that have been projected to the last archaeal common ancestor gene set led to the identification of several novel components of predicted secretion, membrane remodeling, and protein glycosylation systems. Among other findings, most crenarchaea have been shown to encode highly diverged orthologs of the membrane insertase YidC, which is nearly universal in bacteria, eukaryotes, and euryarchaea. We also identified a vast family of archaeal proteins, including the C-terminal domain of N-glycosylation protein AglD, as membrane flippases homologous to the flippase domain of bacterial multipeptide resistance factor MprF, a bifunctional lysylphosphatidylglycerol synthase and flippase. Additionally, several proteins were predicted to function as membrane transporters. The results of this work, combined with our previous analyses, reveal an unexpected diversity of putative archaeal membrane-associated functional systems that remain to be functionally characterized. A more general conclusion from this work is that the currently available collection of archaeal (and bacterial) genomes could be sufficient to identify (almost) all widespread functional modules and develop experimentally testable predictions of their functions. (C) Published by Elsevier B.V.
C1 [Makarova, Kira S.; Galperin, Michael Y.; Koonin, Eugene V.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
RP Makarova, KS (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
EM makarova@ncbi.nlm.nih.gov
FU NIH Intramural Research Program at the National Library of Medicine, US
Department of Health and Human Services
FX We thank Yuri Wolf for providing Perl scripts for genomic neighborhood
analysis and other help. KSM, MYG and EVK are supported by the NIH
Intramural Research Program at the National Library of Medicine, US
Department of Health and Human Services.
NR 81
TC 0
Z9 0
U1 3
U2 10
PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
PI PARIS
PA 23 RUE LINOIS, 75724 PARIS, FRANCE
SN 0300-9084
EI 1638-6183
J9 BIOCHIMIE
JI Biochimie
PD NOV
PY 2015
VL 118
BP 302
EP 312
DI 10.1016/j.biochi.2015.01.004
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA CW5UN
UT WOS:000365062200035
PM 25583072
ER
PT J
AU Peng, L
Chen, XY
AF Peng, Li
Chen, Xiaoyuan
TI Antibody-Drug Conjugates
SO BIOCONJUGATE CHEMISTRY
LA English
DT Editorial Material
C1 [Peng, Li] Medlmmune LLC, Antibody Discovery & Prot Engn, Gaithersburg, MD 20878 USA.
[Chen, Xiaoyuan] NIBIB, Lab Mol Imaging & Nanomed LOMIN, NIH, Bethesda, MD 20892 USA.
RP Peng, L (reprint author), Medlmmune LLC, Antibody Discovery & Prot Engn, One MedImmune Way, Gaithersburg, MD 20878 USA.
EM pengl@medimmune.com; shawn.chen@nih.gov
FU Intramural NIH HHS [Z99 EB999999, ZIA EB000073-07]
NR 0
TC 1
Z9 1
U1 1
U2 13
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1043-1802
J9 BIOCONJUGATE CHEM
JI Bioconjugate Chem.
PD NOV
PY 2015
VL 26
IS 11
SI SI
BP 2169
EP 2169
DI 10.1021/acs.bioconjchem.5b00515
PG 1
WC Biochemical Research Methods; Biochemistry & Molecular Biology;
Chemistry, Multidisciplinary; Chemistry, Organic
SC Biochemistry & Molecular Biology; Chemistry
GA CW6ZX
UT WOS:000365148700001
PM 26577284
ER
PT J
AU Qasba, PK
AF Qasba, Pradman K.
TI Glycans of Antibodies as a Specific Site for Drug Conjugation Using
Glycosyltransferases
SO BIOCONJUGATE CHEMISTRY
LA English
DT Review
ID MUTANT GLYCOSYLTRANSFERASES; OLIGOSACCHARIDE MOIETIES; N-GLYCANS;
BIOCONJUGATION; BIOMOLECULES; CHEMISTRY; RESIDUES; IMMUNOGLOBULINS;
CYCLOADDITIONS; IDENTIFICATION
AB The therapeutic cargo molecules conjugated to a specific site on a monoclonal antibody (mAb), called antibody drug conjugates (ADCs), are becoming powerful tools in cancer treatment. Generally, the cargo molecules conjugate at the cysteine or lysine residue of the mAb, which generally results in a highly heterogeneous ADC. Therapeutic cargo molecules need to be conjugated in a site-specific manner to the mAb so that the bioefficacy of these molecules is not compromised. The mAb (IgG1) are N-glycosylated at the conserved residue Asn(297), which is present in each heavy chain of the IgG1, near the CH2 domain of the Fc fragment. The mutant or wild-type glycosyltransferases transfer sugars with a chemical handle to the glycan molecule of IgG1, making the site-specific linking of cargo molecules possible via the chemical handle, and thus making the process an invaluable technique for the production of homogeneous ADCs.
C1 [Qasba, Pradman K.] NCI, Ctr Canc Res, NIH, Frederick, MD 21702 USA.
RP Qasba, PK (reprint author), NCI, Ctr Canc Res, NIH, Frederick, MD 21702 USA.
EM qasbapr@helix.nih.gov
FU National Cancer Institute, National Institutes of Health [BRL OOTC PID
001.015.0002.0001]
FX The author thanks Ms. Ashley De Vine and Ms. Nancy Parish, Scientific
Publications, Graphics & Media department at NCI-Frederick for editing
the manuscript, which was funded in part with Federal funds from the
National Cancer Institute, National Institutes of Health, under contract
BRL OOTC PID 001.015.0002.0001. The author also thanks all the coworkers
who have contributed to this technology in particular Drs. Boopathy
Ramakrishnan, Elizabeth Boeggeman, Martha Pasek and Natalia Mercer.
NR 39
TC 5
Z9 5
U1 5
U2 14
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1043-1802
J9 BIOCONJUGATE CHEM
JI Bioconjugate Chem.
PD NOV
PY 2015
VL 26
IS 11
SI SI
BP 2170
EP 2175
DI 10.1021/acs.bioconjchem.5b00173
PG 6
WC Biochemical Research Methods; Biochemistry & Molecular Biology;
Chemistry, Multidisciplinary; Chemistry, Organic
SC Biochemistry & Molecular Biology; Chemistry
GA CW6ZX
UT WOS:000365148700002
PM 26065635
ER
PT J
AU Zhu, GZ
Niu, G
Chen, XY
AF Zhu, Guizhi
Niu, Gang
Chen, Xiaoyuan
TI Aptamer-Drug Conjugates
SO BIOCONJUGATE CHEMISTRY
LA English
DT Review
ID IN-VITRO SELECTION; PHOTODYNAMIC CANCER-THERAPY; NUCLEIC-ACID APTAMERS;
STRANDED-DNA APTAMER; NEAR-INFRARED LIGHT; NF-KAPPA-B; RNA APTAMER;
PHOTOTHERMAL THERAPY; TARGETED DELIVERY; LIVE CELLS
AB Western medicine often aims to specifically treat diseased tissues or organs. However, the majority of current therapeutics failed to do so owing to their limited selectivity and the consequent "off-target" side effects. Targeted therapy aims to enhance the selectivity of therapeutic effects and reduce adverse side effects. One approach toward this goal is to utilize disease-specific ligands to guide the delivery of less-specific therapeutics, such that the therapeutic effects can be guided specifically to diseased tissues or organs. Among these ligands, aptamers, also known as chemical antibodies, have emerged over the past decades as a novel class of targeting ligands that are capable of specific binding to disease biomarkers. Compared with other types of targeting ligands, aptamers have an array of unique advantageous features, which make them promising for developing aptamer drug conjugates (ApDCs) for targeted therapy. In this Review, we will discuss ApDCs for targeted drug delivery in chemotherapy, gene therapy, immunotherapy, photodynamic therapy, and photothermal therapy, primarily of cancer.
C1 [Zhu, Guizhi; Niu, Gang; Chen, Xiaoyuan] NIBIB, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA.
RP Chen, XY (reprint author), NIBIB, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD 20892 USA.
EM shawn.chen@nih.gov
FU Intramural NIH HHS [Z99 EB999999, ZIA EB000073-06]
NR 144
TC 17
Z9 17
U1 17
U2 72
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1043-1802
J9 BIOCONJUGATE CHEM
JI Bioconjugate Chem.
PD NOV
PY 2015
VL 26
IS 11
SI SI
BP 2186
EP 2197
DI 10.1021/acs.bioconjchem.5b00291
PG 12
WC Biochemical Research Methods; Biochemistry & Molecular Biology;
Chemistry, Multidisciplinary; Chemistry, Organic
SC Biochemistry & Molecular Biology; Chemistry
GA CW6ZX
UT WOS:000365148700004
PM 26083153
ER
PT J
AU Lawler, M
Siu, LL
Rehm, HL
Chanock, SJ
Alterovitz, G
Burn, J
Calvo, F
Lacombe, D
Teh, BT
North, KN
Sawyers, CL
AF Lawler, Mark
Siu, Lillian L.
Rehm, Heidi L.
Chanock, Stephen J.
Alterovitz, Gil
Burn, John
Calvo, Fabien
Lacombe, Denis
Teh, Bin Tean
North, Kathryn N.
Sawyers, Charles L.
CA Global Alliance Genomics Hlth GA4G
TI All the World's a Stage: Facilitating Discovery Science and Improved
Cancer Care through the Global Alliance for Genomics and Health
SO CANCER DISCOVERY
LA English
DT Editorial Material
AB The recent explosion of genetic and clinical data generated from tumor genome analysis presents an unparalleled opportunity to enhance our understanding of cancer, but this opportunity is compromised by the reluctance of many in the scientific community to share datasets and the lack of interoperability between different data platforms. The Global Alliance for Genomics and Health is addressing these barriers and challenges through a cooperative framework that encourages "team science" and responsible data sharing, complemented by the development of a series of application program interfaces that link different data platforms, thus breaking down traditional silos and liberating the data to enable new discoveries and ultimately benefit patients. (C)2015 AACR.
C1 [Lawler, Mark] Queens Univ Belfast, Ctr Canc Res & Cell Biol, Belfast BT9 7AE, Antrim, North Ireland.
[Siu, Lillian L.] Univ Hlth Network, Toronto, ON, Canada.
[Rehm, Heidi L.; Alterovitz, Gil] Harvard Univ, Sch Med, Boston, MA USA.
[Chanock, Stephen J.] NCI, Div Canc Epidemiol & Genet, Washington, DC USA.
[Burn, John] Newcastle Univ, Inst Med Genet, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England.
[Calvo, Fabien] Canc Core Europe, Villejuif, France.
[Calvo, Fabien] Inst Gustave Roussy, Villejuif, France.
[Lacombe, Denis] European Org Res Treatment Canc, Brussels, Belgium.
[Teh, Bin Tean] Natl Canc Ctr Singapore, Singapore, Singapore.
[North, Kathryn N.] Murdoch Childrens Res Inst, Melbourne, Vic, Australia.
[Sawyers, Charles L.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
RP Lawler, M (reprint author), Queens Univ Belfast, Ctr Canc Res & Cell Biol, CCRCB, Lisburn Rd 97, Belfast BT9 7AE, Antrim, North Ireland.
EM mark.lawler@qub.ac.uk
RI Sawyers, Charles/G-5327-2016; North, Kathryn/K-6476-2012;
OI North, Kathryn/0000-0003-0841-8009; Burn, John/0000-0002-9823-2322
NR 17
TC 7
Z9 7
U1 1
U2 2
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 NOV
PY 2015
VL 5
IS 11
BP 1133
EP 1136
DI 10.1158/2159-8290.CD-15-0821
PG 4
WC Oncology
SC Oncology
GA CX3KJ
UT WOS:000365597400021
PM 26526696
ER
PT J
AU Bluemke, DA
AF Bluemke, David A.
TI Progress in the Diagnosis of Arrhythmogenic Right Ventricular
Cardiomyopathy/Dysplasia by Cardiac Magnetic Resonance Imaging Using
Feature Tracking
SO CIRCULATION-CARDIOVASCULAR IMAGING
LA English
DT Editorial Material
DE Editorials; arrhythmogenic right ventricular cardiomyopathy; cardiac
arrhythmias; dilatation; echocardiography magnetic resonance imaging
C1 [Bluemke, David A.] Natl Inst Biomed Imaging & Bioengn, Radiol & Imaging Sci, NIH, Ctr Clin, Bethesda, MD 21287 USA.
RP Bluemke, DA (reprint author), Natl Inst Biomed Imaging & Bioengn, Radiol & Imaging Sci, NIH, Ctr Clin, 10 Ctr Dr, Bethesda, MD 21287 USA.
EM david.bluemke@nih.gov
OI Bluemke, David/0000-0002-8323-8086
FU Intramural NIH HHS [ZIA CL090019-06, ZIA EB000072-06]
NR 10
TC 0
Z9 1
U1 1
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1941-9651
EI 1942-0080
J9 CIRC-CARDIOVASC IMAG
JI Circ.-Cardiovasc. Imaging
PD NOV
PY 2015
VL 8
IS 11
AR e004167
DI 10.1161/CIRCIMAGING.115.004167
PG 2
WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical
Imaging
SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine &
Medical Imaging
GA CW6WU
UT WOS:000365139900001
PM 26534933
ER
PT J
AU Thomas, C
Avram, A
Pierpaoli, C
Baker, C
AF Thomas, Cibu
Avram, Alexandru
Pierpaoli, Carlo
Baker, Chris
TI Diffusion MRI properties of the human uncinate fasciculus correlate with
the ability to learn visual associations
SO CORTEX
LA English
DT Article
DE Uncinate fasciculus; Diffusion MRI; Tractography
ID INFERIOR TEMPORAL CORTEX; ORBITAL PREFRONTAL CORTEX; CEREBRAL
WHITE-MATTER; RHESUS-MONKEY; FRONTAL-CORTEX; LOBE EPILEPSY; NEURAL
FRAMEWORK; FIBER TRACKING; HUMAN BRAIN; TRACTOGRAPHY
AB The uncinate fasciculus (UF) is a cortico-cortico white matter pathway that links the anterior temporal and the orbitofrontal cortex (OFC). In the monkey, transection of the UP causes significant impairments in learning conditional visual visual associations, while object discrimination remains intact, suggesting an important role for the UP in mediating the learning of complex visual associations. Whether this functional role extends to the human UP has not been tested directly. Here, we used diffusion tensor magnetic resonance imaging (dMRI) and behavioral experiments to examine the relation between learning visual associations and the structural properties of the human UF. In a group of healthy adults, we segmented the UP and the inferior longitudinal fasciculus (ILF) and derived dMRI measures of the structural properties of the two pathways. We also used a behavioral experiment adapted from the monkey studies to characterize the ability of these individuals to learn to associate a person's face with a group of specific scenes (conditional visual visual association). We then tested whether the variability in the dMRI measures of the two pathways correlated with variability in the ability to rapidly learn the face place associations. Our study suggests that in the human, the left UF may be important for mediating the rapid learning of conditional visual visual associations whereas the right UP may play an important role in the immediate retrieval of visual-visual associations. These results provide preliminary evidence suggesting similarities and differences in the functional role of the UP in monkeys compared to humans. The findings presented here contribute to our understanding of the functional role of the UF in humans and the functional neuroanatomy of the brain networks involved in visual cognition. (C) 2015 Elsevier Ltd. All rights reserved.
C1 [Thomas, Cibu; Avram, Alexandru; Pierpaoli, Carlo] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Pediat Imaging & Tissue Sci, Bethesda, MD USA.
[Thomas, Cibu] Uniformed Serv Univ Hlth Sci, Ctr Neurosci & Regenerat Med, Bethesda, MD 20814 USA.
[Thomas, Cibu; Baker, Chris] NIMH, Sect Learning & Plast, Lab Brain & Cognit, Bethesda, MD 20892 USA.
RP Thomas, C (reprint author), NIH, Room 3W16,13 South Dr, Bethesda, MD 20814 USA.
EM thomascp@mail.nih.gov
OI Baker, Chris/0000-0001-6861-8964
FU Intramural Research Programs of NICHD; NIMH [MH002909-07]; Department of
Defense in the Center for Neuroscience and Regenerative Medicine
FX This work was supported by Intramural Research Programs of NICHD and
NIMH (Grant Number MH002909-07). Salary support for CT was provided by
funding from the Department of Defense in the Center for Neuroscience
and Regenerative Medicine. We thank Dr. Joelle Sarlls for assistance
with the diffusion MRI sequence design.
NR 82
TC 5
Z9 5
U1 1
U2 3
PU ELSEVIER MASSON
PI MILANO
PA VIA PALEOCAPA 7, 20121 MILANO, ITALY
SN 0010-9452
EI 1973-8102
J9 CORTEX
JI Cortex
PD NOV
PY 2015
VL 72
SI SI
BP 65
EP 78
DI 10.1016/j.cortex.2015.01.023
PG 14
WC Behavioral Sciences; Neurosciences
SC Behavioral Sciences; Neurosciences & Neurology
GA CW5SQ
UT WOS:000365057300007
PM 25742710
ER
PT J
AU Simanek, AM
Meier, HCS
AF Simanek, Amanda M.
Meier, Helen C. S.
TI Association Between Prenatal Exposure to Maternal Infection and
Offspring Mood Disorders: A Review of the Literature
SO CURRENT PROBLEMS IN PEDIATRIC AND ADOLESCENT HEALTH CARE
LA English
DT Article
ID TOXOPLASMA-GONDII INFECTION; HERPES-SIMPLEX-VIRUS; MAJOR
AFFECTIVE-DISORDER; COMORBIDITY SURVEY REPLICATION; DEPRESSION-RELATED
BEHAVIORS; GRAY-MATTER VOLUME; BIPOLAR DISORDER; UNITED-STATES; IMMUNE
ACTIVATION; NERVOUS-SYSTEM
AB The purpose of this article is to provide a systematic review of studies that have examined the association between prenatal exposure to maternal infection and development of mood disorders across the life course. Drawing from both human- and animal-based studies, we give an overview of hypothesized biological mechanisms by which exposure to maternal infection during critical periods of gestation may contribute to fetal programming of mood disorders in offspring. We discuss studies examining the association between prenatal exposure to maternal infection with pathogens including influenza as well as other respiratory viruses, herpesviruses, hepatitis viruses, and Toxoplasma gondii and mood disorders in human populations. Moreover, we outline strengths and limitations of the current body of evidence and make recommendations for future research. We also discuss findings in the context of well-documented gender and socioeconomic disparities in the prevalence and severity of mood disorders, particularly major depression, and the role that early exposure to infection may play in explaining the perpetuation of such disparities across generations. Overall, this review of the current knowledge on this topic has important implications for determining future research directions, designing interventions as well as prenatal care guidelines targeted at prevention or treatment of infection during pregnancy, and clinical practice for the identification of individuals that may be at increased risk for mood disorders beginning early in life. Importantly, such efforts may not only lower the overall burden of mood disorders but also serve to address social disparities in these adverse mental health conditions in the U.S.
C1 [Simanek, Amanda M.] Univ Wisconsin, Joseph J Zilber Sch Publ Hlth, Milwaukee, WI 53201 USA.
[Meier, Helen C. S.] NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA.
RP Simanek, AM (reprint author), Univ Wisconsin, Joseph J Zilber Sch Publ Hlth, Milwaukee, WI 53201 USA.
FU National Institutes of Health, United States; National Institute of
Environmental Health Sciences, United States
FX H.C.S.M was supported by the intramural research program of the National
Institutes of Health, United States and National Institute of
Environmental Health Sciences, United States.
NR 162
TC 6
Z9 6
U1 10
U2 16
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1538-5442
EI 1538-3199
J9 CURR PROB PEDIATR AD
JI Curr. Probl. Pediatr. Adolesc. Health Care
PD NOV
PY 2015
VL 45
IS 11
BP 325
EP 364
DI 10.1016/j.cppeds.2015.06.008
PG 40
WC Pediatrics
SC Pediatrics
GA CW4TU
UT WOS:000364985800002
PM 26476880
ER
PT J
AU Cung, W
Freedman, LA
Khan, NE
Romberg, E
Gardner, PJ
Bassim, CW
Baldwin, AM
Widemann, BC
Stewart, DR
AF Cung, Winnie
Freedman, Laura A.
Khan, Nicholas E.
Romberg, Elaine
Gardner, Pamela J.
Bassim, Carol W.
Baldwin, Andrea M.
Widemann, Brigitte C.
Stewart, Douglas R.
TI Cephalometry in adults and children with neurofibromatosis type 1:
Implications for the pathogenesis of sphenoid wing dysplasia and the
"NF1 facies"
SO EUROPEAN JOURNAL OF MEDICAL GENETICS
LA English
DT Article
DE Neurofibromatosis type 1; Cephalometery; Dysmorphology; Sphenoid wing
dysplasia
ID CRANIAL BASE; GROWTH; ABNORMALITIES
AB Background: Neurofibromatosis type 1 (NF1) is a common, autosomal dominant tumor-predisposition disorder that arises secondary to mutations in the tumor suppressor gene NF1. Cephalometry is an inexpensive, readily available and non-invasive technique that is under-utilized in studying the NF1 craniofacial phenotype. An analysis of NF1 cephalometry was first published by Heerva et al. in 2011. We expand here on that first investigation with a larger cohort of adult and pediatric patients affected with NF1 and sought objective insight into the NF1 facies, said to feature hypertelorism and a broad nasal base, from cephalometric analysis.
Methods: We obtained cephalograms from 101 patients with NF1 (78 adults and 23 children) from two NF1 protocols at the National Institutes of Health. Each subject had an age-, gender- and ethnicity-matched control. We used Dolphin software to make the cephalometric measurements. We assessed the normality of differences between paired samples using the Shapiro-Wilk test and evaluated the significance of mean differences using paired t-tests and adjusted for multiple testing. We explored the relationship between the cephalometric measurements and height, head circumference and interpupillary distance.
Results: In this dataset of American whites with NF1, we confirmed in a modestly larger sample many of the findings found by Heerva et al. in an NF1 Finnish cohort. We found a shorter maxilla, mandible, cranial base, (especially anteriorly, p = 0.0001) and diminished facial height in adults, but not children, with NF1. Only one adult exhibited hypertelorism.
Conclusions: The cephalometric differences in adults arise in part from cranial base shortening and thus result in a shorter face, mid-face hypoplasia, reduced facial projection, smaller jaw, and increased braincase globularity. In addition, we suggest that NF1 sphenoid bone shortening, a common event, is consistent with an intrinsic NF1 bone cell defect, which renders the bone more vulnerable to a random "second hit" in NF1, leading to sphenoid wing dysplasia, a rare event. Published by Elsevier Masson SAS.
C1 [Cung, Winnie; Freedman, Laura A.; Romberg, Elaine] Univ Maryland, Sch Dent, Baltimore, MD 21201 USA.
[Khan, Nicholas E.; Stewart, Douglas R.] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA.
[Gardner, Pamela J.; Bassim, Carol W.] Natl Inst Dent & Craniofacial Res, Dent Consult Serv, NIH, Bethesda, MD USA.
[Baldwin, Andrea M.; Widemann, Brigitte C.] NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA.
RP Stewart, DR (reprint author), 9609 Med Ctr Dr Rm 6E450, Bethesda, MD 20892 USA.
EM drstewart@mail.nih.gov
FU Division of Cancer Epidemiology and Genetics (DCEG); Center for Cancer
Research of the National Cancer Institute's Intramural Research Program
FX This work was supported by the Division of Cancer Epidemiology and
Genetics (DCEG) and the Center for Cancer Research of the National
Cancer Institute's Intramural Research Program. We thank Janice Lee DDS,
MD (NIDCR) for helpful discussions.
NR 24
TC 1
Z9 1
U1 0
U2 2
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1769-7212
EI 1878-0849
J9 EUR J MED GENET
JI Eur. J. Med. Genet.
PD NOV
PY 2015
VL 58
IS 11
BP 584
EP 590
DI 10.1016/j.ejmg.2015.09.001
PG 7
WC Genetics & Heredity
SC Genetics & Heredity
GA CW9WP
UT WOS:000365349200004
PM 26360873
ER
PT J
AU Elentner, A
Ortner, D
Clausen, BE
Gonzalez, FJ
Fernandez-Salguero, PM
Schmuth, M
Dubrac, S
AF Elentner, Andreas
Ortner, Daniela
Clausen, Bjoern E.
Gonzalez, Frank J.
Fernandez-Salguero, Pedro M.
Schmuth, Matthias
Dubrac, Sandrine
TI Skin response to a carcinogen involves the xenobiotic receptor pregnane
X receptor
SO EXPERIMENTAL DERMATOLOGY
LA English
DT Article
DE DNA damage; H2AX; Langerhans cells; pregnane X receptor; skin
ID POLYCYCLIC AROMATIC-HYDROCARBONS; SQUAMOUS-CELL CARCINOMA; IN-VITRO
ALTERNATIVES; LANGERHANS CELLS; CONTACT HYPERSENSITIVITY; METABOLISM
CAPACITIES; CHEMICAL CARCINOGENS; NUCLEAR RECEPTORS; HAIR FOLLICLE;
DNA-DAMAGE
AB Skin is in daily contact with potentially harmful molecules from the environment such as cigarette smoke, automobile emissions, industrial soot and groundwater. Pregnane X receptor (PXR) is a transcription factor expressed in liver and intestine that is activated by xenobiotic chemicals including drugs and environmental pollutants. Topical application of the tumor initiator 7,12-dimethylbenz(a)anthracene (DMBA) enhances Pxr, Cyp1a1, Cyp1b1 and Cyp3a11, but not Ahr expression in the skin. Surprisingly, DMBA-induced Pxr upregulation is largely impaired in Langerin(+) cell-depleted skin, suggesting that DMBA mainly triggers Pxr in Langerin(+) cells. Furthermore, PXR deficiency protects from DNA damage in epidermal cells but to a lesser extent than aryl hydrocarbon receptor (AHR) deficiency. Interestingly, skin exposure to low doses of DMBA induces migration of PXR-deficient but not of wild-type and AHR-deficient Langerhans cells (LCs). PXR-humanized mice show a marked increase in DNA damage to epidermal cells after topical application of DMBA, demonstrating relevance of these findings in human tissue. This is the first report suggesting that carcinogens might trigger PXR in epidermal cells, particularly in LCs, thus leading to DNA damage. Further studies are required to better delineate the role of PXR in cutaneous carcinogenesis.
C1 [Elentner, Andreas; Ortner, Daniela; Schmuth, Matthias; Dubrac, Sandrine] Med Univ Innsbruck, Dept Dermatol & Venereol, A-6020 Innsbruck, Austria.
[Clausen, Bjoern E.] Johannes Gutenberg Univ Mainz, Univ Med Ctr, Inst Mol Med, D-55122 Mainz, Germany.
[Gonzalez, Frank J.] NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Fernandez-Salguero, Pedro M.] Univ Extremadura, Fac Sci, Dept Biochem Mol Biol & Genet, Badajoz, Spain.
RP Dubrac, S (reprint author), Med Univ Innsbruck, Dept Dermatol & Venereol, A-6020 Innsbruck, Austria.
EM sandrine.dubrac@i-med.ac.at
RI CLAUSEN, Bjorn/A-8229-2010;
OI CLAUSEN, Bjorn/0000-0002-2484-7842; Fernandez-Salguero, Pedro
M./0000-0003-2839-5027
FU Austrian Science Fund [FWF P-21449]
FX This work was supported by a grant from the Austrian Science Fund to
S.D. (FWF P-21449). AE, DO and SD performed assays; BC, FJG and PMF
contributed essential mouse strains and participated in paper writing,
MS and SD designed the research study, analysed the data and wrote the
paper.
NR 47
TC 4
Z9 4
U1 1
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0906-6705
EI 1600-0625
J9 EXP DERMATOL
JI Exp. Dermatol.
PD NOV
PY 2015
VL 24
IS 11
BP 835
EP 840
DI 10.1111/exd.12766
PG 6
WC Dermatology
SC Dermatology
GA CX0RL
UT WOS:000365404300006
PM 26013842
ER
PT J
AU Almeida-Suhett, CP
Prager, EM
Pidoplichko, V
Figueiredo, TH
Marini, AM
Li, Z
Eiden, LE
Braga, MFM
AF Almeida-Suhett, Camila P.
Prager, Eric M.
Pidoplichko, Volodymyr
Figueiredo, Taiza H.
Marini, Ann M.
Li, Zheng
Eiden, Lee E.
Braga, Maria F. M.
TI GABAergic interneuronal loss and reduced inhibitory synaptic
transmission in the hippocampal CM region after mild traumatic brain
injury
SO EXPERIMENTAL NEUROLOGY
LA English
DT Article
DE Mild traumatic brain injury; CA1; Synaptic transmission; Controlled
cortical impact; Cognitive impairment
ID LONG-TERM POTENTIATION; CLOSED-HEAD-INJURY; PROFESSIONAL FOOTBALL
PLAYERS; CONTROLLED CORTICAL IMPACT; FLUID PERCUSSION INJURY; GABA(A)
RECEPTOR; COGNITIVE DEFICITS; RETROGRADE-AMNESIA; MEMORY IMPAIRMENT;
NMDA RECEPTOR
AB Patients that suffer mild traumatic brain injuries (mTBI) often develop cognitive impairments, including memory and learning deficits. The hippocampus shows a high susceptibility to mTBI-induced damage due to its anatomical localization and has been implicated in cognitive and neurological impairments after mTBI. However, it remains unknown whether mTBI cognitive impairments are a result of morphological and pathophysiological alterations occurring in the CA1 hippocampal region. We investigated whether mTBI induces morphological and pathophysiological alterations in the CA1 using the controlled cortical impact (CCI) model. Seven days after CCI, animals subjected to mTBI showed cognitive impairment in the passive avoidance test and deficits to long-term potentiation (LTP) of synaptic transmission. Deficiencies in inducing or maintaining LTP were likely due to an observed reduction in the activation of NMDA but not AMPA receptors. Significant reductions in the frequency and amplitude of spontaneous and miniature GABA(A)-receptor mediated inhibitory postsynaptic currents (IPSCs) were also observed 7 days after CCI. Design-based stereology revealed that although the total number of neurons was unaltered, the number of GABAergic interneurons is significantly reduced in the CA1 region 7 days after CCI. Additionally, the surface expression of alpha 1, beta 2/3, and gamma 2 subunits of the GABA(A) receptor were reduced, contributing to a reduced mIPSC frequency and amplitude, respectively. Together, these results suggest that mTBI causes a significant reduction in GABAergic inhibitory transmission and deficits to NMDA receptor mediated currents in the CA1, which may contribute to changes in hippocampal excitability and subsequent cognitive impairments after mTBI. Published by Elsevier Inc.
C1 [Almeida-Suhett, Camila P.; Prager, Eric M.; Marini, Ann M.; Braga, Maria F. M.] Uniformed Serv Univ Hlth Sci, F Edward Hebert Sch Med, Program Neurosci, Bethesda, MD 20814 USA.
[Pidoplichko, Volodymyr; Figueiredo, Taiza H.; Braga, Maria F. M.] Uniformed Serv Univ Hlth Sci, F Edward Hebert Sch Med, Dept Anat Physiol & Genet, Bethesda, MD 20814 USA.
[Marini, Ann M.] Uniformed Serv Univ Hlth Sci, F Edward Hebert Sch Med, Dept Neurol, Bethesda, MD 20814 USA.
[Braga, Maria F. M.] Uniformed Serv Univ Hlth Sci, F Edward Hebert Sch Med, Dept Psychiat, Bethesda, MD 20814 USA.
[Almeida-Suhett, Camila P.; Marini, Ann M.; Li, Zheng; Eiden, Lee E.; Braga, Maria F. M.] Uniformed Serv Univ Hlth Sci, F Edward Hebert Sch Med, Ctr Neurosci & Regenerat Med, Bethesda, MD 20814 USA.
[Li, Zheng] NIMH, Sect Clin Studies, Intramural Res Program, Bethesda, MD 20892 USA.
[Eiden, Lee E.] NIMH, Sect Mol Neurosci, Intramural Res Program, Bethesda, MD 20892 USA.
RP Braga, MFM (reprint author), Uniformed Serv Univ Hlth Sci, F Edward Hebert Sch Med, Dept Psychiat, Dept Anat Physiol & Genet, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA.
EM camila.almeida.ctr@usuhs.edu; eprager@wiley.com;
volodymyr.pidoplichko.ctr@usuhs.edu; taiza.figueiredo.ctr@usuhs.edu;
ann.marini@usuhs.edu; Lizheng2@mail.nih.gov; eidenl@mail.nih.gov;
maria.braga@usuhs.edu
FU Department of Defense in the Center for Neuroscience and Regenerative
Medicine [G1702Z]
FX The authors acknowledge the Department of Defense in the Center for
Neuroscience and Regenerative Medicine for financially supporting the
present work. Grant# G1702Z. URL of funder's website:
http://www.usuhs.mil/cnrm/. The funders had no role in study design,
data collection and analysis, decision to publish, or preparation of the
manuscript.
NR 135
TC 10
Z9 10
U1 2
U2 3
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0014-4886
EI 1090-2430
J9 EXP NEUROL
JI Exp. Neurol.
PD NOV
PY 2015
VL 273
BP 11
EP 23
DI 10.1016/j.expneurol.2015.07.028
PG 13
WC Neurosciences
SC Neurosciences & Neurology
GA CW7BB
UT WOS:000365151800002
PM 26238734
ER
PT J
AU Eitan, E
Hutchison, ER
Greig, NH
Tweedie, D
Celik, H
Ghosh, S
Fishbein, KW
Spencer, RG
Sasaki, CY
Ghosh, P
Das, S
Chigurapati, S
Raymick, J
Sarkar, S
Chigurupati, S
Seal, S
Mattson, MP
AF Eitan, Erez
Hutchison, Emmette R.
Greig, Nigel H.
Tweedie, David
Celik, Hasan
Ghosh, Soumita
Fishbein, Kenneth W.
Spencer, Richard G.
Sasaki, Carl Y.
Ghosh, Paritosh
Das, Soumen
Chigurapati, Susheela
Raymick, James
Sarkar, Sumit
Chigurupati, Srinivasulu
Seal, Sudipta
Mattson, Mark P.
TI Combination therapy with lenalidomide and nanoceria ameliorates CNS
autoimmunity
SO EXPERIMENTAL NEUROLOGY
LA English
DT Article
DE Cerebral ventricles; Cerium oxide nanoparticles; Demyelination; EAE;
Multiple sclerosis
ID CERIUM OXIDE NANOPARTICLES; PROGRESSIVE MULTIPLE-SCLEROSIS; GLATIRAMER
ACETATE; MOUSE MODEL; THALIDOMIDE; ENCEPHALOMYELITIS; MECHANISM;
DISEASE; NEURODEGENERATION; DEMYELINATION
AB Objective: Multiple sclerosis (MS) is a debilitating neurological disorder involving an autoimmune reaction to oligodendrocytes and degeneration of the axons they ensheath in the CNS. Because the damage to oligodendrocytes and axons involves local inflammation and associated oxidative stress, we tested the therapeutic efficacy of combined treatment with a potent anti-inflammatory thalidomide analog (lenalidomide) and novel synthetic anti-oxidant cerium oxide nanoparticles (nanoceria) in the experimental autoimmune encephalomyelitis (EAE) mouse model of MS.
Methods: C57BL/6 mice were randomly assigned to a control (no EAE) group, or one of the four myelin oligodendrocyte glycoprotein-induced EAE groups: vehicle, lenalidomide, nanoceria, or lenalidomide plus nanoceria. During a 23 day period, clinical EAE symptoms were evaluated daily, and MRI brain scans were performed at 11-13 days and 20-22 days. Histological and biochemical analyses of brain tissue samples were performed to quantify myelin loss and local inflammation.
Results: Lenalidomide treatment alone delayed symptom onset, while nanoceria treatment had no effect on symptom onset or severity, but did promote recovery; lenalidomide and nanoceria each significantly attenuated white matter pathology and associated inflammation. Combined treatment with lenalidomide and nanoceria resulted in a near elimination of EAE symptoms, and reduced white matter pathology and inflammatory cell responses to a much greater extent than either treatment alone.
Interpretation: By suppressing inflammation and oxidative stress, combined treatment with lenalidomide and nanoceria can reduce demyelination and associated neurological symptoms in EAE mice. Our preclinical data suggest a potential application of this combination therapy in MS. Published by Elsevier Inc.
C1 [Eitan, Erez; Hutchison, Emmette R.; Mattson, Mark P.] NIA, Lab Neurosci, Intramural Res Program, Baltimore, MD 21224 USA.
[Greig, Nigel H.; Tweedie, David] NIA, Translat Gerontol Branch, Intramural Res Program, Baltimore, MD 21224 USA.
[Celik, Hasan; Ghosh, Soumita; Fishbein, Kenneth W.; Spencer, Richard G.] NIA, Lab Clin Invest, Intramural Res Program, Baltimore, MD 21224 USA.
[Das, Soumen] Univ Cent Florida, Mat Sci & Engn Coll Med, Orlando, FL 32816 USA.
[Sasaki, Carl Y.; Ghosh, Paritosh] NIA, Immunol Lab, Intramural Res Program, Baltimore, MD 21224 USA.
[Chigurapati, Susheela] US FDA, Arkansas Reg Lab, Off Regulatory Affairs, Jefferson, AR 72079 USA.
[Raymick, James; Sarkar, Sumit; Chigurupati, Srinivasulu] US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA.
[Seal, Sudipta] Univ Cent Florida, Mech Mat Aerosp Engn, Nanosci Technol Ctr, Adv Mat Proc & Anal Ctr, Orlando, FL 32816 USA.
[Mattson, Mark P.] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA.
RP Mattson, MP (reprint author), NIA, Lab Neurosci, Intramural Res Program, Baltimore, MD 21224 USA.
EM mark.mattson@nih.gov
OI Fishbein, Kenneth/0000-0002-6353-4603
FU National Institute on Aging
FX This research was supported by the Intramural Research Program of the
National Institute on Aging.
NR 41
TC 4
Z9 4
U1 1
U2 6
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0014-4886
EI 1090-2430
J9 EXP NEUROL
JI Exp. Neurol.
PD NOV
PY 2015
VL 273
BP 151
EP 160
DI 10.1016/j.expneurol.2015.08.008
PG 10
WC Neurosciences
SC Neurosciences & Neurology
GA CW7BB
UT WOS:000365151800014
PM 26277686
ER
PT J
AU Azoury, SC
Aufforth, R
He, M
Yang, ZM
Nilubol, N
Kebebew, E
AF Azoury, Said C.
Aufforth, Rachel
He, Mei
Yang, Zhiming
Nilubol, Naris
Kebebew, Electron
TI Quantitative reverse transcription polymerase chain reaction-based
detection of thyroid-specific gene expression in fine-needle aspirate
for thyroid cancer recurrence evaluation: A case report and review of
the literature
SO HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND
NECK
LA English
DT Article
DE thyroid cancer; fine-needle aspirate; polymerase chain reaction (PCR);
recurrence; diagnosis
ID SODIUM-IODIDE SYMPORTER; CERVICAL LYMPH-NODES; MEDIAN FOLLOW-UP; SERUM
THYROGLOBULIN; NECK ULTRASONOGRAPHY; CARCINOMA; PAPILLARY; DIAGNOSIS;
MANAGEMENT; DISEASE
AB Background. Despite improved surveillance for patients after total thyroidectomy for cancer, there has yet to be a diagnostic method that detects recurrence with 100% accuracy.
Methods. A 60-year-old woman with a family history of papillary thyroid cancer (PTC) underwent total thyroidectomy and radioactive iodine ablation. On postoperative surveillance, ultrasound examination of the neck demonstrated a focus concerning for recurrence and a fine-needle aspirate (FNA) was performed. The cytology report was nondiagnostic and, hence, RNA was extracted from the specimen followed by reverse transcription (cDNA), and quantitative real-time polymerase chain reaction (qRT-PCR) to detect thyroid-specific gene expression (thyroglobulin = Tg; sodium-iodide symporter = NIS; thyroperoxidase = TPO).
Results. Expression of select thyroid-specific genes was demonstrated, and given the patient's remarkable cancer and family history, surgical resection was elected. Final pathology demonstrated follicular adenoma.
Conclusion. This case demonstrates a novel approach used in the evaluation for recurrent thyroid cancer as an adjunct to FNA cytology. (C) 2015 Wiley Periodicals, Inc.
C1 [Azoury, Said C.] NCI, Surg Branch, NIH, Bethesda, MD 20892 USA.
[Azoury, Said C.] Johns Hopkins Univ, Johns Hopkins Hosp, Sch Med, Dept Surg, Baltimore, MD 21287 USA.
[Aufforth, Rachel; He, Mei; Nilubol, Naris; Kebebew, Electron] NCI, Endocrine Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Yang, Zhiming] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Azoury, SC (reprint author), Johns Hopkins Univ, Johns Hopkins Hosp, Sch Med, Dept Surg, 600 N Wolfe St,Blalock 658, Baltimore, MD 21287 USA.
EM sazoury1@jhmi.edu
NR 38
TC 0
Z9 0
U1 0
U2 2
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 NOV
PY 2015
VL 37
IS 11
BP E165
EP E168
DI 10.1002/hed.24054
PG 4
WC Otorhinolaryngology; Surgery
SC Otorhinolaryngology; Surgery
GA CX0SD
UT WOS:000365406100008
PM 25784309
ER
PT J
AU Ferencik, M
Liu, T
Mayrhofer, T
Puchner, SB
Lu, MT
Maurovich-Horvat, P
Pope, JH
Truong, QA
Udelson, JE
Peacock, WF
White, CS
Woodard, PK
Fleg, JL
Nagurney, JT
Januzzi, JL
Hoffmann, U
AF Ferencik, Maros
Liu, Ting
Mayrhofer, Thomas
Puchner, Stefan B.
Lu, Michael T.
Maurovich-Horvat, Pal
Pope, J. Hector
Truong, Quynh A.
Udelson, James E.
Peacock, W. Frank
White, Charles S.
Woodard, Pamela K.
Fleg, Jerome L.
Nagurney, John T.
Januzzi, James L.
Hoffmann, Udo
TI hs-Troponin I Followed by CT Angiography Improves Acute Coronary
Syndrome Risk Stratification Accuracy and Work-Up in Acute Chest Pain
Patients Results From ROMICAT II Trial
SO JACC-CARDIOVASCULAR IMAGING
LA English
DT Article
DE acute coronary syndrome; coronary computed tomography angiography;
coronary plaque; emergency department; highly sensitive troponin; risk
stratification
ID SENSITIVITY CARDIAC TROPONIN; ACUTE MYOCARDIAL-INFARCTION;
COMPUTED-TOMOGRAPHY ANGIOGRAPHY; EARLY-DIAGNOSIS; EMERGENCY-DEPARTMENT;
SERIAL CHANGES; ASSAY; RULE; RECLASSIFICATION; ASSOCIATION
AB OBJECTIVES This study compared diagnostic accuracy of conventional troponin/traditional coronary artery disease (CAD) assessment and highly sensitive troponin (hsTn) I/advanced CAD assessment for acute coronary syndrome (ACS) during the index hospitalization.
BACKGROUND hsTnI and advanced assessment of CAD using coronary computed tomography angiography (CTA) are promising candidates to improve the accuracy of emergency department evaluation of patients with suspected ACS.
METHODS We performed an observational cohort study in patients with suspected ACS enrolled in the ROMICAT II (Rule Out Myocardial Infarction/Ischemia using Computer Assisted Tomography) trial and randomized to coronary CTA who also had hsTnI measurement at the time of the emergency department presentation. We assessed coronary CTA for traditional (no CAD, nonobstructive CAD, >= 50% stenosis) and advanced features of CAD (>= 50% stenosis, high-risk plaque features: positive remodeling, low <30-Hounsfield units plaque, napkin-ring sign, spotty calcium).
RESULTS Of 160 patients (mean age: 53 +/- 8 years, 40% women) 10.6% were diagnosed with ACS. The ACS rate in patients with hsTnI below the limit of detection (n = 9, 5.6%), intermediate (n = 139, 86.9%), and above the 99th percentile (n = 12, 7.5%) was 0%, 8.6%, and 58.3%, respectively. Absence of >= 50% stenosis and high-risk plaque ruled out ACS in patients with intermediate hsTnI (n = 87, 54.4%; ACS rate 0%), whereas patients with both >= 50% stenosis and high-risk plaque were at high risk (n = 13, 8.1%; ACS rate 69.2%) and patients with either >= 50% stenosis or high-risk plaque were at intermediate risk for ACS (n = 39, 24.4%; ACS rate 7.7%). hsTnI/advanced coronary CTA assessment significantly improved the diagnostic accuracy for ACS as compared to conventional troponin/traditional coronary CTA (area under the curve 0.84, 95% confidence interval [CI]: 0.80 to .88 vs. 0.74, 95% CI: 0.70 to 0.78; p < 0.001).
CONCLUSIONS hsTnI at the time of presentation followed by early advanced coronary CTA assessment improves the risk stratification and diagnostic accuracy for ACS as compared to conventional troponin and traditional coronary CTA assessment. (C) 2015 by the American College of Cardiology Foundation.
C1 [Ferencik, Maros] Oregon Hlth & Sci Univ, Knight Cardiovasc Inst, Portland, OR 97239 USA.
[Ferencik, Maros; Liu, Ting; Mayrhofer, Thomas; Puchner, Stefan B.; Lu, Michael T.; Truong, Quynh A.; Hoffmann, Udo] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Ferencik, Maros; Liu, Ting; Mayrhofer, Thomas; Puchner, Stefan B.; Lu, Michael T.; Truong, Quynh A.; Nagurney, John T.; Januzzi, James L.; Hoffmann, Udo] Harvard Univ, Sch Med, Boston, MA USA.
[Ferencik, Maros; Liu, Ting; Mayrhofer, Thomas; Puchner, Stefan B.; Lu, Michael T.; Truong, Quynh A.; Hoffmann, Udo] Massachusetts Gen Hosp, Cardiac MR PET CT Program, Boston, MA 02114 USA.
[Liu, Ting] China Med Univ, Dept Radiol, Affiliated Hosp 1, Shenyang 110001, Peoples R China.
[Puchner, Stefan B.] Med Univ Vienna, Dept Biomed Imaging & Image Guided Therapy, Vienna, Austria.
[Maurovich-Horvat, Pal] Semmelweis Univ, Heart & Vasc Ctr, TA SE Lendulet Cardiovasc Imaging Res Grp, H-1085 Budapest, Hungary.
[Pope, J. Hector] Baystate Med Ctr, Dept Emergency Med, Springfield, MA USA.
[Truong, Quynh A.] New York Presbyterian Hosp, Dalio Inst Cardiovasc Imaging, New York, NY USA.
[Truong, Quynh A.] Weill Cornell Med Coll, New York, NY USA.
[Udelson, James E.] Tufts Med Ctr, Div Cardiol, Boston, MA USA.
[Udelson, James E.] Tufts Med Ctr, Ctr Cardiovasc, Boston, MA USA.
[Peacock, W. Frank] Baylor Coll Med, Dept Emergency Med, Houston, TX 77030 USA.
[White, Charles S.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA.
[Woodard, Pamela K.] Washington Univ, Sch Med, Mallinckrodt Inst Radiol, St Louis, MO USA.
[Fleg, Jerome L.] NHLBI, Div Cardiovasc Sci, Bethesda, MD 20892 USA.
[Nagurney, John T.] Massachusetts Gen Hosp, Dept Emergency Med, Boston, MA 02114 USA.
[Januzzi, James L.; Hoffmann, Udo] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
RP Ferencik, M (reprint author), Oregon Hlth & Sci Univ, Knight Cardiovasc Inst, 3180 Sam Jackson Pk Rd,Mail Code UHN62, Portland, OR 97239 USA.
EM ferencik@ohsu.edu
FU National Institutes of Health, ACRIN [NIH U01HL092040, U01HL092022];
American Heart Association [13FTF16450001]; NIH/NHLBI [K23HL098370,
L30HL093896]; St. Jude Medical; American College of Radiology Imaging
Network; Duke Clinical Research; Abbott; Alere; Banyan; Cardiorentis;
Portola; Roche; Medicines Company; Siemens; Thermo Fisher; Singulex; NIH
[U01HL092022, U01HL092040]; Siemens Medical Solutions; Heart Flow Inc.;
Alere/Biosite; Brahms Ltd/Thermo-Fisher; Nanosphere
FX The ROMICAT II trial is supported by the National Institutes of Health
grant numbers NIH U01HL092040 and U01HL092022, ACRIN. The content of
this paper is solely the responsibility of the authors and does not
necessarily reflect the views of the National Institutes of Health or
the Department of Health and Human Services. Dr. Ferencik has received a
research grant from the American Heart Association Fellow to Faculty
Award 13FTF16450001. Dr. Truong has received research grants from
NIH/NHLBI K23HL098370 and L30HL093896, St. Jude Medical, American
College of Radiology Imaging Network, and Duke Clinical Research. Dr.
Peacock has received research grants from Abbott, Alere, Banyan,
Cardiorentis, Portola, Roche, and The Medicines Company; has ownership
of Comprehensive Research Associates LLC and Emergencies in Medicine
LLC; is a consultant with and on advisory boards for BG Medicine,
Beckman, Boehringer-Ingelheim, Instrument Labs, Prevencio, The Medicines
Company, ZS Pharma, Alere, Cardiorentis, and Janssen. Dr. Nagumey has
received research grants from Alere/Biosite, Brahms Ltd/Thermo-Fisher,
Nanosphere; is a consultant for and on advisory board at CardioDx. Dr.
Januzzi received research grants from Siemens, Thermo Fisher, and
Singulex; is a consultant with and on advisory board of Critical
Diagnostics, Sphingotec, and Roche. Dr. Hoffmann received research
grants from NIH U01HL092040, U01HL092022, Siemens Medical Solutions,
Heart Flow Inc.; and is a consultant for and on advisory board of Heart
Flow. All other authors have reported that they have no relationships
relevant to the contents of this paper to disclose. Drs. Ferencik and
Liu contributed equally to this work.
NR 26
TC 7
Z9 7
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1936-878X
EI 1876-7591
J9 JACC-CARDIOVASC IMAG
JI JACC-Cardiovasc. Imag.
PD NOV
PY 2015
VL 8
IS 11
BP 1272
EP 1281
DI 10.1016/j.jcmg.2015.06.016
PG 10
WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical
Imaging
SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine &
Medical Imaging
GA CW7AS
UT WOS:000365150900007
PM 26476506
ER
PT J
AU Guy, GP
Berkowitz, Z
Holman, DM
Hartman, AM
AF Guy, Gery P., Jr.
Berkowitz, Zahava
Holman, Dawn M.
Hartman, Anne M.
TI Recent Changes in the Prevalence of and Factors Associated With
Frequency of Indoor Tanning Among US Adults
SO JAMA DERMATOLOGY
LA English
DT Letter
C1 [Guy, Gery P., Jr.; Berkowitz, Zahava; Holman, Dawn M.] Ctr Dis Control & Prevent, Div Canc Prevent & Control, Atlanta, GA 30341 USA.
[Hartman, Anne M.] NCI, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA.
RP Guy, GP (reprint author), Ctr Dis Control & Prevent, Div Canc Prevent & Control, 4770 Buford Hwy NE,Mail Stop F76, Atlanta, GA 30341 USA.
EM irm2@cdc.gov
FU Intramural CDC HHS [CC999999]
NR 7
TC 12
Z9 12
U1 0
U2 1
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 2168-6068
EI 2168-6084
J9 JAMA DERMATOL
JI JAMA Dermatol.
PD NOV
PY 2015
VL 151
IS 11
BP 1256
EP 1259
DI 10.1001/jamadermatol.2015.1568
PG 5
WC Dermatology
SC Dermatology
GA CW9GD
UT WOS:000365305900024
PM 26131768
ER
PT J
AU Konc, J
Miller, BT
Stular, T
Lesnik, S
Woodcock, HL
Brooks, BR
Janezic, D
AF Konc, Janez
Miller, Benjamin T.
Stular, Tanja
Lesnik, Samo
Woodcock, H. Lee
Brooks, Bernard R.
Janezic, Dusanka
TI ProBiS-CHARMMing: Web Interface for Prediction and Optimization of
Ligands in Protein Binding Sites
SO JOURNAL OF CHEMICAL INFORMATION AND MODELING
LA English
DT Article
ID GENERAL FORCE-FIELD; LOCAL-STRUCTURE ALIGNMENT; REPLICA-EXCHANGE METHOD;
MOLECULAR-DYNAMICS; EXPLICIT SOLVENT; DOCKING SCREENS; USER-INTERFACE;
DRUG DESIGN; SIMULATION; ALGORITHM
AB Proteins often exist only as apo structures (unligated) in the Protein Data Bank, with their corresponding holo structures (with ligands) unavailable. However, apoproteins may not represent the amino-acid residue arrangement upon ligand binding well, which is especially problematic for molecular docking. We developed the ProBiS-CHARMMing web interface by connecting the ProBiS (http://probis.cmm.ki.si) and CHARMMing (http://www.charmining.org) web servers into one functional unit that enables prediction of protein-ligand complexes and allows for their geometry optimization and interaction energy calculation. The ProBiS web server predicts ligands (small compounds, proteins, nucleic acids, and single-atom ligands) that may bind to a query protein. This is achieved by comparing its surface structure against a nonredundant database of protein structures and finding those that have binding sites similar to that of the query protein. Existing ligands found in the similar binding sites are then transposed to the query according to predictions from ProBiS. The CHARMMing web server enables, among other things, minimization and potential energy calculation for a wide variety of biomolecular systems, and it is used here to optimize the geometry of the predicted protein ligand complex structures using the CHARMM force field and to calculate their interaction energies with the corresponding query proteins. We show how ProBiS-CHARMMing can be used to predict ligands and their poses for a particular binding site, and minimize the predicted protein ligand complexes to obtain representations of holoproteins. The ProBiS-CHA_RMMing web interface is freely available for academic users at http://probis. nih.gov.
C1 [Konc, Janez; Lesnik, Samo] Natl Inst Chem, Lab Mol Modeling, SI-1000 Ljubljana, Slovenia.
[Konc, Janez; Stular, Tanja; Janezic, Dusanka] Univ Primorska, Fac Math Nat Sci & Informat Technol, SI-6000 Koper, Slovenia.
[Miller, Benjamin T.; Brooks, Bernard R.] NHLBI, Lab Computat Biol, Biochem & Biophys Ctr, NIH, Bethesda, MD 20892 USA.
[Woodcock, H. Lee] Univ S Florida, Dept Chem, Tampa, FL 33620 USA.
RP Janezic, D (reprint author), Univ Primorska, Fac Math Nat Sci & Informat Technol, Glagoljaska 8, SI-6000 Koper, Slovenia.
EM dusanka.janezic@upr.si
FU Slovenian Research Agency [P1-0002, J1-6743]; DOE [DE-SC0011297]; NSF
[CHE-1464946]; National Heart, Lung, and Blood Institute, NIH
FX The financial support through Grant Nos. P1-0002 and J1-6743 of the
Slovenian Research Agency is acknowledged. J.K. acknowledges the
Fulbright Scholarship at the National Heart, Lung, and Blood Institute,
NIH. H.L.W. would like to acknowledge the DOE (No. DE-SC0011297) and NSF
(No. CHE-1464946) for Funding. Support by the Intramural Research
Program of the National Heart, Lung, and Blood Institute, NIH, is also
acknowledged.
NR 42
TC 6
Z9 6
U1 2
U2 7
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1549-9596
EI 1549-960X
J9 J CHEM INF MODEL
JI J. Chem Inf. Model.
PD NOV
PY 2015
VL 55
IS 11
BP 2308
EP 2314
DI 10.1021/acs.jcim.5b00534
PG 7
WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Computer Science,
Information Systems; Computer Science, Interdisciplinary Applications
SC Pharmacology & Pharmacy; Chemistry; Computer Science
GA CX1OL
UT WOS:000365465400002
PM 26509288
ER
PT J
AU Briggs-Gowan, MJ
Pollak, SD
Grasso, D
Voss, J
Mian, ND
Zobel, E
McCarthy, KJ
Wakschlag, LS
Pine, DS
AF Briggs-Gowan, Margaret J.
Pollak, Seth D.
Grasso, Damion
Voss, Joel
Mian, Nicholas D.
Zobel, Elvira
McCarthy, Kimberly J.
Wakschlag, Lauren S.
Pine, Daniel S.
TI Attention bias and anxiety in young children exposed to family violence
SO JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY
LA English
DT Article
DE Attention bias; violence; harsh parenting; early childhood; anxiety;
fear
ID DIAGNOSTIC-OBSERVATION-SCHEDULE; PRESCHOOL DISRUPTIVE BEHAVIOR;
CONFLICT-TACTICS-SCALES; MALTREATED CHILDREN; PSYCHOMETRIC DATA;
DISORDERS; SYMPTOMS; STRESS; THREAT; PSYCHOPATHOLOGY
AB Background: Attention bias toward threat is associated with anxiety in older youth and adults and has been linked with violence exposure. Attention bias may moderate the relationship between violence exposure and anxiety in young children. Capitalizing on measurement advances, this study examines these relationships at a younger age than previously possible. Methods: Young children (mean age 4.7, +/- 0.8) from a cross-sectional sample oversampled for violence exposure (N = 218) completed the dot-probe task to assess their attention biases. Observed fear/anxiety was characterized with a novel observational paradigm, the Anxiety Dimensional Observation Scale. Mother-reported symptoms were assessed with the Preschool Age Psychiatric Assessment and Trauma Symptom Checklist for Young Children. Violence exposure was characterized with dimensional scores reflecting probability of membership in two classes derived via latent class analysis from the Conflict Tactics Scales: Abuse and Harsh Parenting. Results: Family violence predicted greater child anxiety and trauma symptoms. Attention bias moderated the relationship between violence and anxiety. Conclusions: Attention bias toward threat may strengthen the effects of family violence on the development of anxiety, with potentially cascading effects across childhood. Such associations may be most readily detected when using observational measures of childhood anxiety.
C1 [Briggs-Gowan, Margaret J.; Grasso, Damion; McCarthy, Kimberly J.] Univ Connecticut, Sch Med, Dept Psychiat, Farmington, CT 06030 USA.
[Pollak, Seth D.] Univ Wisconsin, Dept Psychol, Madison, WI 53706 USA.
[Pollak, Seth D.] Univ Wisconsin, Waisman Ctr, Madison, WI 53705 USA.
[Voss, Joel; Zobel, Elvira; Wakschlag, Lauren S.] Northwestern Univ, Feinberg Sch Med, Dept Med Social Sci, Chicago, IL 60611 USA.
[Mian, Nicholas D.] Boston Univ, Dept Psychol, Ctr Anxiety & Related Disorders, Boston, MA 02215 USA.
[Wakschlag, Lauren S.] Northwestern Univ, Inst Policy Res, Chicago, IL 60611 USA.
[Pine, Daniel S.] NIMH, Div Intramural Res Programs, Bethesda, MD 20892 USA.
RP Briggs-Gowan, MJ (reprint author), Univ Connecticut, Ctr Hlth, Dept Psychiat, 263 Farmington Ave,MC-1410, Farmington, CT 06030 USA.
EM mbriggsgowan@uchc.edu
FU National Institute of Mental Health [U01MH090301, R01MH082830]
FX Financial support for the study was provided by grants from the National
Institute of Mental Health (U01MH090301; R01MH082830). The authors thank
Jackie Kestler and Kimberly McCarthy for their hard work and dedication
to supporting this study. The authors have declared that they have no
competing or potential conflicts of interest.
NR 37
TC 6
Z9 6
U1 10
U2 32
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 NOV
PY 2015
VL 56
IS 11
BP 1194
EP 1201
DI 10.1111/jcpp.12397
PG 8
WC Psychology, Developmental; Psychiatry; Psychology
SC Psychology; Psychiatry
GA CX0UA
UT WOS:000365411200007
PM 26716142
ER
PT J
AU Schwartz, AV
Chen, HY
Ambrosius, WT
Sood, A
Josse, RG
Bonds, DE
Schnall, AM
Vittinghoff, E
Bauer, DC
Banerji, MA
Cohen, RM
Hamilton, BP
Isakova, T
Sellmeyer, DE
Simmons, DL
Shibli-Rahhal, A
Williamson, JD
Margolis, KL
AF Schwartz, Ann V.
Chen, Haiying
Ambrosius, Walter T.
Sood, Ajay
Josse, Robert G.
Bonds, Denise E.
Schnall, Adrian M.
Vittinghoff, Eric
Bauer, Douglas C.
Banerji, Mary Ann
Cohen, Robert M.
Hamilton, Bruce P.
Isakova, Tamara
Sellmeyer, Deborah E.
Simmons, Debra L.
Shibli-Rahhal, Amal
Williamson, Jeff D.
Margolis, Karen L.
TI Effects of TZD Use and Discontinuation on Fracture Rates in ACCORD Bone
Study
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID RANDOMIZED CONTROLLED-TRIAL; IMPAIRED GLUCOSE-TOLERANCE; MINERAL
DENSITY; POSTMENOPAUSAL WOMEN; DIABETES-MELLITUS; ROSIGLITAZONE;
PIOGLITAZONE; RISK; THIAZOLIDINEDIONES; METAANALYSIS
AB Context: In trials, thiazolidinediones (TZDs) increase fracture risk in women, but the effects of discontinuation are unknown.
Objective: The objective was to investigate the effects of TZD use and discontinuation on fractures in women and men.
Design: This was a longitudinal observational cohort study using data from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial bone ancillary study. Duration of TZD use and discontinuation during ACCORD, assessed every 2-4 months at clinic visits, were modeled as timevarying covariates in proportional hazards models for occurrence of first non-spine fracture.
Participants: We studied a total of 6865 participants in ACCORD BONE.
Main Outcome Measures: Main outcome measures were centrally adjudicated non-spine fracture.
Results: Average age was 62.4 (SD, 6.6) years; average duration of diabetes was 11.1 (SD, 7.8) years. Rosiglitazone was used by 74% and pioglitazone by 13% of participants. During a mean follow-up of 4.8 (SD, 1.5) years, 262 men and 287 women experienced at least one non-spine fracture. The fracture rate was higher in women with 1-2 years of TZD use (hazard ratio [HR] = 2.32; 95% confidence interval [CI], 1.49, 3.62) or > 2 years of TZD use (HR = 2.01; 95% CI, 1.35, 2.98), compared with no use. The fracture rate was reduced in women who had discontinued TZD use for 1-2 years (HR = 0.57; 95% CI, 0.35, 0.92) or > 2 years (HR = 0.42; 95% CI, 0.24, 0.74) compared with current users. TZD use and discontinuation were not associated with non-spine fractures in men.
Conclusions: TZD use was associated with increased non-spine fractures in women, but not men, with type 2 diabetes. When women discontinued TZD use, the fracture effects were attenuated.
C1 [Schwartz, Ann V.; Vittinghoff, Eric; Bauer, Douglas C.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Chen, Haiying; Ambrosius, Walter T.; Williamson, Jeff D.] Wake Forest Sch Med, Winston Salem, NC 27157 USA.
[Sood, Ajay] Louis Stokes VA Med Ctr, Cleveland, OH 44106 USA.
[Sood, Ajay; Schnall, Adrian M.] Case Western Reserve Univ, Cleveland, OH 44106 USA.
[Josse, Robert G.] St Michaels Hosp, Toronto, ON M5B 1W8, Canada.
[Bonds, Denise E.] NHLBI, NIH, Bethesda, MD 20892 USA.
[Banerji, Mary Ann] Suny Downstate Med Ctr, Brooklyn, NY 11203 USA.
[Banerji, Mary Ann] Kings Cty Hosp, Brooklyn, NY 11203 USA.
[Cohen, Robert M.] Univ Cincinnati, Coll Med, Cincinnati, OH 45267 USA.
[Hamilton, Bruce P.] VA Med Ctr, Baltimore, MD 21201 USA.
[Hamilton, Bruce P.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA.
[Isakova, Tamara] Univ Miami, Miami, FL 33124 USA.
[Sellmeyer, Deborah E.] Johns Hopkins Sch Med, Div Endocrinol, Baltimore, MD 21205 USA.
[Simmons, Debra L.] Univ Utah, Salt Lake City, UT 84148 USA.
[Simmons, Debra L.] Salt Lake City Vet Hosp, Salt Lake City, UT 84148 USA.
[Shibli-Rahhal, Amal] Univ Iowa, Carver Coll Med, Iowa City, IA 52242 USA.
[Margolis, Karen L.] Hlth Partners Inst Educ & Res, Minneapolis, MN 55425 USA.
RP Schwartz, AV (reprint author), Univ Calif San Francisco, Mission Hall,550 16th St,Second Floor, San Francisco, CA 94158 USA.
EM aschwartz@psg.ucsf.edu
FU National Institute of Diabetes and Digestive and Kidney Diseases
[R01DK069514]; National Heart, Lung, and Blood Institute [N01-HC-95178,
N01-HC-95179, N01- HC-95180, N01-HC-95181, N01-HC-95182, N01-HC-95183,
N01- HC-95184, IAA-Y1-HC-9035, IAA-Y1-HC-1010]; National Institutes of
Health, National Institute of Diabetes and Digestive and Kidney
Diseases; National Institutes of Health, National Institute on Aging;
National Institutes of Health, National Eye Institute; Centers for
Disease Control and Prevention; General Clinical Research Centers
FX The ACCORD BONE ancillary study was funded by a grant (R01DK069514) from
the National Institute of Diabetes and Digestive and Kidney Diseases.
The ACCORD study was supported by grants (N01-HC-95178, N01-HC-95179,
N01- HC-95180, N01-HC-95181, N01-HC-95182, N01-HC-95183, N01- HC-95184,
IAA-Y1-HC-9035, and IAA-Y1-HC-1010) from the National Heart, Lung, and
Blood Institute; by other components of the National Institutes of
Health, including the National Institute of Diabetes and Digestive and
Kidney Diseases, the National Institute on Aging, and the National Eye
Institute; by the Centers for Disease Control and Prevention; and by
General Clinical Research Centers. The following companies provided
study medications, equipment, or supplies: Abbott Laboratories, Amylin
Pharmaceutical, AstraZeneca, Bayer HealthCare, Closer Healthcare,
GlaxoSmithKline, King Pharmaceuticals, Merck, Novartis, Novo Nordisk,
Omron Healthcare, Sanofi-Aventis, and Schering-Plough.
NR 27
TC 6
Z9 7
U1 0
U2 1
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0021-972X
EI 1945-7197
J9 J CLIN ENDOCR METAB
JI J. Clin. Endocrinol. Metab.
PD NOV
PY 2015
VL 100
IS 11
BP 4059
EP 4066
DI 10.1210/jc.2015-1215
PG 8
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA CW3XM
UT WOS:000364925700033
PM 26305617
ER
PT J
AU Zarek, SM
Mitchell, EM
Sjaarda, LA
Mumford, SL
Silver, RM
Stanford, JB
Galai, N
White, MV
Schliep, KC
DeCherney, AH
Schisterman, EF
AF Zarek, Shvetha M.
Mitchell, Emily M.
Sjaarda, Lindsey A.
Mumford, Sunni L.
Silver, Robert M.
Stanford, Joseph B.
Galai, Noya
White, Mark V.
Schliep, Karen C.
DeCherney, Alan H.
Schisterman, Enrique F.
TI Is Anti-Mullerian Hormone Associated With Fecundability? Findings From
the EAGeR Trial
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID POLYCYSTIC-OVARY-SYNDROME; REVISED 2003 CONSENSUS; ANTIMULLERIAN
HORMONE; DIAGNOSTIC-CRITERIA; EUMENORRHEIC WOMEN; OOCYTE QUALITY;
PREGNANCY; AGE; RESERVE; TIME
AB Objective: The objective of the study was to evaluate whether anti-Mullerian hormone (AMH) is associated with fecundability among women with proven fecundity and a history of pregnancy loss.
Design: This was a prospective cohort study within a multicenter, block-randomized, double-blind, placebo-controlled clinical trial (clinicaltrials.gov, number NCT00467363).
Setting: The study was conducted at four US medical centers (2006-2012).
Participants: Participating women were aged 18-40 years, with a history of one to two pregnancy losses who were actively attempting pregnancy.
Main Outcome Measures: Time to human chorionic gonadotropin detected and clinical pregnancy were assessed using Cox proportional hazard regression models to estimate fecundability odds ratios (fecundability odds ratios with 95% confidence interval [CI]) adjusted for age, race, body mass index, income, low-dose aspirin treatment, parity, number of previous losses, and time since most recent loss. Analyses examined by preconception AMH levels: low (<1.00 ng/mL, n = 124); normal (referent 1.00-3.5 ng/mL, n = 595); and high (>3.5 ng/mL, n = 483).
Results: Of the 1202 women with baseline AMH levels, 82 women with low AMH (66.1%) achieved an human chorionic gonadotropin detected pregnancy, compared with 383 with normal AMH (65.2%) and 315 with high AMH level (65.2%). Low or high AMH levels relative to normal AMH (referent) were not associated with fecundability (low AMH: fecundability odds ratios 1.13, 95% CI 0.85-1.49; high AMH: FOR 1.04, 95% CI 0.87-1.24).
Conclusions: Lower and higher AMH values were not associated with fecundability in unassisted conceptions in a cohort of fecund women with a history of one or two prior losses. Our data do not support routine AMH testing for preconception counseling in young, fecund women.
C1 [Zarek, Shvetha M.; Mitchell, Emily M.; Sjaarda, Lindsey A.; Mumford, Sunni L.; Schliep, Karen C.; Schisterman, Enrique F.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Intramural Populat Hlth Res, Rockville, MD 20854 USA.
[Zarek, Shvetha M.; DeCherney, Alan H.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, Bethesda, MD 20982 USA.
[Silver, Robert M.; Stanford, Joseph B.] Univ Utah, Dept Obstet & Gynecol, Salt Lake City, UT 84111 USA.
Intermt HealthCare, Salt Lake City, UT 84111 USA.
[Galai, Noya] Univ Haifa, Dept Stat, IL-3498838 Haifa, Israel.
[White, Mark V.] Commonwealth Med Coll, Dept Family Community & Rural Hlth, Scranton, PA 18509 USA.
RP Schisterman, EF (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Intramural Populat Hlth Res, 6100 Executive Blvd,7B03, Rockville, MD 20854 USA.
EM schistee@mail.nih.gov
OI Sjaarda, Lindsey/0000-0003-0539-8110; Schisterman,
Enrique/0000-0003-3757-641X
FU Intramural Research Program of the Eunice Kennedy Shriver National
Institute of Child Health and Human Development, National Institutes of
Health [HHSN267200603423, HHSN267200603424, HHSN267200603426]
FX This work was supported by the Intramural Research Program of the Eunice
Kennedy Shriver National Institute of Child Health and Human
Development, National Institutes of Health (Contracts HHSN267200603423,
HHSN267200603424, and HHSN267200603426).
NR 43
TC 4
Z9 4
U1 0
U2 2
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0021-972X
EI 1945-7197
J9 J CLIN ENDOCR METAB
JI J. Clin. Endocrinol. Metab.
PD NOV
PY 2015
VL 100
IS 11
BP 4215
EP 4221
DI 10.1210/jc.2015-2474
PG 7
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA CW3XM
UT WOS:000364925700052
PM 26406293
ER
PT J
AU Shen, J
Poole, JC
Topel, ML
Bidulescu, A
Morris, AA
Patel, RS
Binongo, JG
Dunbar, SB
Phillips, L
Vaccarino, V
Gibbons, GH
Quyyumi, AA
AF Shen, Jia
Poole, Joseph C.
Topel, Matthew L.
Bidulescu, Aurelian
Morris, Alanna A.
Patel, Riyaz S.
Binongo, Jose G.
Dunbar, Sandra B.
Phillips, Lawrence
Vaccarino, Viola
Gibbons, Gary H.
Quyyumi, Arshed A.
TI Subclinical Vascular Dysfunction Associated with Metabolic Syndrome in
African Americans and Whites
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID ALL-CAUSE MORTALITY; ARTERIAL STIFFNESS; NITRIC-OXIDE;
CARDIOVASCULAR-DISEASE; RISK-FACTORS; CORONARY ATHEROSCLEROSIS;
ENDOTHELIAL DYSFUNCTION; ESSENTIAL-HYPERTENSION; REACTIVE HYPEREMIA;
INSULIN-RESISTANCE
AB Context: The diagnosis of metabolic syndrome (MetS) identifies individuals at risk for developing diabetes and cardiovascular disease. African Americans (AAs) have high rates of cardiovascular disease and subclinical vascular disease including arterial stiffness and microvascular dysfunction but have relatively low rates of MetS.
Objective: The objective of the study was to evaluate the relationship between MetS and vascular function in a biracial cohort with the hypothesis that the diagnosis of MetS underestimates sub-clinical vascular disease in AAs.
Design: We measured components of MetS in a community-based cohort of 951 AAs and white subjects (aged 48.8 +/- 11 y, 47% AA, 55% female).
Main Outcome Measures: Using digital pulse amplitude tonometry, we estimated the reactive hyperemia index (RHI), a measure of microvascular endothelial function. Using applanation tonometry (Sphygmocor), central augmentation index (CAIx) and pulse wave velocity (PWV) were measured as indices of wave reflections and arterial stiffness, respectively.
Results: MetS was present in 24.0% of subjects and was associated with increased PWV (P < .001) and CAIx (P < .001) and a trend to lower RHI (P = .068) in both races. However, in subjects without MetS, AAs had lower RHI (P < .001) and higher PWV (P = .003) and CAIx (P = .002) compared with white subjects. Addition of an extra MetS criterion point for AAs with hypertension eliminated the racial differences in PWV and CAIx but not RHI.
Conclusion: Although MetS is associated with microvascular dysfunction and increased arterial stiffness in both racial groups, AAs without MetS have greater vascular dysfunction compared with whites. Additional weighting for hypertension in AAs attenuated the racial differences in sub-clinical disease associated with MetS.
C1 [Shen, Jia; Poole, Joseph C.; Morris, Alanna A.; Vaccarino, Viola; Quyyumi, Arshed A.] Emory Clin Cardiovasc Res Inst, Atlanta, GA 30322 USA.
[Topel, Matthew L.; Phillips, Lawrence] Emory Univ, Sch Med, Atlanta, GA 30322 USA.
[Binongo, Jose G.] Emory Rollins Sch Publ Hlth, Dept Biostat & Bioinformat, Atlanta, GA 30322 USA.
[Dunbar, Sandra B.] Emory Univ, Sch Nursing, Atlanta, GA 30322 USA.
[Bidulescu, Aurelian] Morehouse Sch Med, Cardiovasc Res Inst, Atlanta, GA 30310 USA.
[Patel, Riyaz S.] UCL, Inst Cardiovasc Sci, London WC1 6BT, England.
[Gibbons, Gary H.] NHLBI, NIH, Bethesda, MD 20824 USA.
RP Quyyumi, AA (reprint author), Div Cardiol, Med, 1462 Clifton Rd NE,Suite 510, Atlanta, GA 30322 USA.
EM aquyyum@emory.edu
FU National Institutes of Health/National Heart, Lung, and Blood Institute
Grant [1 U01 HL079156-01, 1 U01 HL79214-01]; National Institutes of
Health from the Clinical and Translational Science Award program for the
Emory Clinical Interaction Unit [UL1 RR025008]; National Institutes of
Health/National Center for Research Resources [5P20RR11104]; Woodruff
Fund
FX This work was supported by funding from National Institutes of
Health/National Heart, Lung, and Blood Institute Grant 1 U01 HL079156-01
(to A.A.Q.) and Grant 1 U01 HL79214-01 (to G.H.G.); in part by National
Institutes of Health Grant UL1 RR025008 from the Clinical and
Translational Science Award program for the Emory Clinical Interaction
Unit; National Institutes of Health/National Center for Research
Resources Grant 5P20RR11104 (to the Morehouse Clinical Research Center);
and the Woodruff Fund (to the Emory Predictive Health Initiative).
NR 45
TC 1
Z9 1
U1 0
U2 0
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0021-972X
EI 1945-7197
J9 J CLIN ENDOCR METAB
JI J. Clin. Endocrinol. Metab.
PD NOV
PY 2015
VL 100
IS 11
BP 4231
EP 4239
DI 10.1210/jc.2014-4344
PG 9
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA CW3XM
UT WOS:000364925700054
PM 26151335
ER
PT J
AU Gourgari, E
Lodish, M
Shamburek, R
Keil, M
Wesley, R
Walter, M
Sampson, M
Bernstein, S
Khurana, D
Lyssikatos, C
Ten, S
Dobs, A
Remaley, AT
Stratakis, CA
AF Gourgari, E.
Lodish, M.
Shamburek, R.
Keil, M.
Wesley, R.
Walter, M.
Sampson, M.
Bernstein, S.
Khurana, D.
Lyssikatos, C.
Ten, S.
Dobs, A.
Remaley, A. T.
Stratakis, C. A.
TI Lipoprotein Particles in Adolescents and Young Women With PCOS Provide
Insights Into Their Cardiovascular Risk
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID POLYCYSTIC-OVARY-SYNDROME; LOW-DENSITY-LIPOPROTEIN; C-REACTIVE PROTEIN;
INSULIN-RESISTANCE; CAROTID ATHEROSCLEROSIS; ADIPOSE-TISSUE; ATHEROGENIC
DYSLIPIDEMIA; METABOLIC SYNDROME; ADIPONECTIN LEVELS; OBESE ADOLESCENTS
AB Context: Adult women with polycystic ovarian syndrome (PCOS) have an increased risk for cardiovascular disease, but the evidence for this is controversial in adolescents and young women with PCOS. Measurement of low-density lipoprotein (LDL) particle number, measured by nuclear magnetic resonance spectroscopy is a novel technology to assess cardiovascular risk.
Objective: The objective of the study was to evaluate lipoprotein particle number and size in young women with PCOS and its relationship with insulin resistance and hyperandrogenism.
Design: This was a cross-sectional case control study.
Setting: The study was conducted at a clinical research center.
Participants: Women with PCOS (n = 35) and normal controls (n = 20) participated in the study.
Interventions: Blood samples and anthropometric measures were obtained.
Main Outcome Measures: LDL particle size and number were measured using nuclear magnetic resonance spectroscopy. A secondary outcome was to investigate the correlation of LDL particle number with high-sensitivity C-reactive protein, waist to hip ratio, hyperandrogenism, insulin resistance, and adiponectin.
Results: Women with PCOS had higher LDL particle number when compared with healthy controls (935 +/- 412 vs 735 +/- 264, P = .032); LDL particle number correlated strongly with high-sensitivity C-reactive protein (r = 0.37, P = .006) and waist-to-hip (r = 0.57, P = .0003). The higher LDL particle number was driven mainly due to differences in the small LDL particle number (sLDLp), with PCOS patients having more sLDLp (348 +/- 305 vs 178 +/- 195, P = .015). The sLDLp correlated with the Matsuda index (r = -0.51, P = .0001), homeostasis model assessment index of insulin resistance (r = 0.41, P = .002), and adiponectin (r = -0.46, P = .0004) but not with T.
Conclusion: Adolescent and young women with PCOS have an atherogenic lipoprotein profile suggestive of increased cardiovascular risk that appears to be driven by the degree of visceral adiposity and insulin resistance.
C1 [Gourgari, E.; Lodish, M.; Keil, M.; Bernstein, S.; Lyssikatos, C.; Stratakis, C. A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Dev Endocrinol & Genet, Sect Endocrinol & Genet, Bethesda, MD 20892 USA.
Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pediat Endocrinol Interinst Training Program, Bethesda, MD 20892 USA.
[Walter, M.] NIDDK, Sect Clin Lab Serv, Bethesda, MD 20892 USA.
[Gourgari, E.] Georgetown Univ, Med Ctr, Div Pediat Endocrinol, Washington, DC 20057 USA.
[Shamburek, R.; Sampson, M.; Remaley, A. T.] NHLBI, Sect Lipoprot Metab, Bethesda, MD 20824 USA.
[Wesley, R.] NIH, Biostat & Clin Epidemiol Serv, Ctr Clin, Bethesda, MD 20814 USA.
[Walter, M.] SUNY, Infants & Childrens Hosp Brooklyn Maimonides, Div Pediat Endocrinol, Brooklyn, NY 11219 USA.
SUNY, Children & Hosp Downstate, Brooklyn, NY 11219 USA.
[Khurana, D.; Ten, S.; Dobs, A.] Johns Hopkins Univ, Sch Med, Dept Endocrinol, Baltimore, MD 21205 USA.
RP Gourgari, E (reprint author), MedStar Georgetown Univ Hosp, Div Pediat Endocrinol, 4200 Wisconsin Ave NW,Fourth Floor, Washington, DC 20016 USA.
EM evgenia.gourgari@gunet.georgetown.edu
FU Eunice Kennedy Shriver National Institute of Child and Health and Human
Development, the National Institutes of Health Clinical Center;
Bench-to-Bedside Program of the National Institutes of Health; Office of
Research on Women's Health, Office of the Director, National Institutes
of Health
FX This work was supported by the Intramural Research Programs of the
Eunice Kennedy Shriver National Institute of Child and Health and Human
Development, the National Institutes of Health Clinical Center, the
Bench-to-Bedside Program of the National Institutes of Health, and the
Office of Research on Women's Health, Office of the Director, National
Institutes of Health.
NR 41
TC 2
Z9 3
U1 0
U2 3
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 NOV
PY 2015
VL 100
IS 11
BP 4291
EP 4298
DI 10.1210/jc.2015-2566
PG 8
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA CW3XM
UT WOS:000364925700061
PM 26371381
ER
PT J
AU Masur, H
Read, SW
AF Masur, Henry
Read, Sarah W.
TI Opportunistic Infections and Mortality: Still Room for Improvement
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Editorial Material
DE HIV; opportunistic infections; pneumocystis pneumonia; life expectancy;
mortality
ID COMBINATION ANTIRETROVIRAL THERAPY; UNITED-STATES; ERA; ASSOCIATION;
ILLNESSES; SURVIVAL; OUTCOMES; COHORT; CARE
C1 [Masur, Henry] NIAID, Dept Crit Care Med, Ctr Clin, NIH, Bethesda, MD 20892 USA.
[Read, Sarah W.] NIAID, Div Aids, NIH, Bethesda, MD 20892 USA.
RP Masur, H (reprint author), NIH, Dept Crit Care Med, Ctr Clin, 10 Ctr Dr,Rm 2C145, Bethesda, MD 20892 USA.
EM hmasur@nih.gov
NR 15
TC 3
Z9 3
U1 1
U2 1
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0022-1899
EI 1537-6613
J9 J INFECT DIS
JI J. Infect. Dis.
PD NOV 1
PY 2015
VL 212
IS 9
BP 1348
EP 1350
DI 10.1093/infdis/jiv236
PG 3
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA CW1QX
UT WOS:000364767500002
PM 26044290
ER
PT J
AU Pombo, C
Wherry, EJ
Gostick, E
Price, DA
Betts, MR
AF Pombo, Carolina
Wherry, E. John
Gostick, Emma
Price, David A.
Betts, Michael R.
TI Elevated Expression of CD160 and 2B4 Defines a Cytolytic HIV-Specific
CD8(+) T-Cell Population in Elite Controllers
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
DE HIV; elite controllers; T-cell exhaustion; PD-1; CD160; 2B4; CD8(+) T
cells
ID POLYCHROMATIC FLOW-CYTOMETRY; HERPESVIRUS ENTRY MEDIATOR; CHRONIC
VIRAL-INFECTION; INHIBITORY RECEPTORS; CYTOKINE PRODUCTION;
UP-REGULATION; EXHAUSTION; ACTIVATION; PD-1; NONPROGRESSORS
AB During chronic human immunodeficiency virus (HIV) infection, virus-specific CD8(+) T cells become functionally exhausted. Unlike most chronically infected individuals, elite controllers of HIV retain CD8(+) T-cell polyfunctionality and cytolytic capacity. It remains unclear whether elite controllers manifest T-cell exhaustion similar to subjects with chronic progression of HIV infection. Here we assessed coexpression of PD-1, Lag-3, CD160, and 2B4 as a measure of T-cell exhaustion in a cohort of elite controllers and in chronic progressors. We found that elite controllers have a high proportion of potentially exhausted (PD1(+)CD160(+)2B4(+)) HIV-specific CD8(+) T cells that is comparable to the proportion in chronic progressors. However, elite controllers also harbor a population of HIV-specific CD160(+)2B4(+) CD8(+) T cells that correlates with cytolytic capacity, as measured by perforin expression, a population not commonly present in chronic progressors. We therefore propose that coexpression of CD160 and 2B4 delineates a population of cytolytic CD8(+) T cells important for the control of HIV.
C1 [Pombo, Carolina; Wherry, E. John; Betts, Michael R.] Univ Penn, Dept Microbiol, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Wherry, E. John] Univ Penn, Inst Immunol, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Price, David A.] NIAID, Human Immunol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Gostick, Emma; Price, David A.] Cardiff Univ, Sch Med, Inst Infect & Immun, Cardiff CF10 3AX, S Glam, Wales.
RP Betts, MR (reprint author), Univ Penn, Microbiol, 522E Johnson Pavil,3610 Hamilton Walk, Philadelphia, PA 19104 USA.
EM betts@mail.med.upenn.edu
RI Price, David/C-7876-2013
OI Price, David/0000-0001-9416-2737
FU National Institutes of Health [R01 A1076066]; National Institutes of
Health (HIV training grant) [T32 AI 07632]; Wellcome Trust
FX This work was supported by the National Institutes of Health (grant R01
A1076066 to M. R. B. and C. P. and HIV training grant T32 AI 07632 to C.
P.) and the Wellcome Trust (to D. A. P.).
NR 50
TC 6
Z9 6
U1 1
U2 3
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0022-1899
EI 1537-6613
J9 J INFECT DIS
JI J. Infect. Dis.
PD NOV 1
PY 2015
VL 212
IS 9
BP 1376
EP 1386
DI 10.1093/infdis/jiv226
PG 11
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA CW1QX
UT WOS:000364767500006
PM 25883386
ER
PT J
AU Sciaranghella, G
Wang, CW
Hu, HH
Anastos, K
Merhi, Z
Nowicki, M
Stanczyk, FZ
Greenblatt, RM
Cohen, M
Golub, ET
Watts, DH
Alter, G
Young, MA
Tsibris, AMN
AF Sciaranghella, Gaia
Wang, Cuiwei
Hu, Haihong
Anastos, Kathryn
Merhi, Zaher
Nowicki, Marek
Stanczyk, Frank Z.
Greenblatt, Ruth M.
Cohen, Mardge
Golub, Elizabeth T.
Watts, D. Heather
Alter, Galit
Young, Mary A.
Tsibris, Athe M. N.
TI CCR5 Expression Levels in HIV-Uninfected Women Receiving Hormonal
Contraception
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
DE HIV-1; hormonal contraception; CCR5; medroxyprogesterone acetate;
levonorgestrel; oral contraceptive pills; peripheral blood mononuclear
cells; CD4; CXCR4
ID HUMAN-IMMUNODEFICIENCY-VIRUS; INTRAUTERINE SYSTEM; RISK;
RADIOIMMUNOASSAY; FITNESS; COHORT; ENTRY
AB Human immunodeficiency virus (HIV) infectivity increases as receptor/coreceptor expression levels increase. We determined peripheral CD4, CCR5, and CXCR4 expression levels in HIV-uninfected women who used depot medroxyprogesterone acetate (DMPA; n = 32), the levonorgestrel-releasing intrauterine device (LNG-IUD; n = 27), oral contraceptive pills (n = 32), or no hormonal contraception (n = 33). The use of LNG-IUD increased the proportion of CD4(+) and CD8(+) T cells that expressed CCR5; increases in the magnitude of T-cell subset CCR5 expression were observed with DMPA and LNG-IUD use (P < .01 for all comparisons). LNG-IUD and, to a lesser extent, DMPA use were associated with increased peripheral T-cell CCR5 expression.
C1 [Sciaranghella, Gaia; Alter, Galit] MIT, Ragon Inst MGH, Boston, MA USA.
[Sciaranghella, Gaia; Alter, Galit] Harvard Univ, Boston, MA 02115 USA.
[Tsibris, Athe M. N.] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Wang, Cuiwei; Hu, Haihong; Tsibris, Athe M. N.] Harvard Univ, Sch Med, Boston, MA USA.
[Wang, Cuiwei; Hu, Haihong; Young, Mary A.] Georgetown Univ, Med Ctr, Washington, DC 20007 USA.
[Anastos, Kathryn] Albert Einstein Coll Med, Dept Med, Bronx, NY 10467 USA.
[Anastos, Kathryn] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA.
[Merhi, Zaher] NYU, Sch Med, Dept Obstet & Gynecol, Div Reprod Biol, New York, NY 10016 USA.
[Nowicki, Marek] Univ So Calif, Keck Sch Med, Dept Med, Los Angeles, CA 90033 USA.
[Stanczyk, Frank Z.] Univ So Calif, Keck Sch Med, Dept Obstet & Gynecol, Los Angeles, CA 90033 USA.
[Stanczyk, Frank Z.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA.
[Greenblatt, Ruth M.] Univ Calif San Francisco, Dept Clin Pharm, San Francisco, CA 94143 USA.
[Greenblatt, Ruth M.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA.
[Greenblatt, Ruth M.] Univ Calif San Francisco, Dept Biostat, San Francisco, CA 94143 USA.
[Greenblatt, Ruth M.] Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94143 USA.
[Cohen, Mardge] Stroger Hosp, Dept Med, Chicago, IL USA.
[Cohen, Mardge] Rush Univ, Dept Med, Chicago, IL 60612 USA.
[Cohen, Mardge] CORE Ctr, Chicago, IL USA.
[Golub, Elizabeth T.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Watts, D. Heather] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
RP Tsibris, AMN (reprint author), Harvard Univ, Sch Med, Dept Med, Div Infect Dis,Brigham & Womens Hosp, 65 Landsdowne St,Rm 422, Cambridge, MA 02139 USA.
EM atsibris@partners.org
FU NIH; National Institute of Allergy and Infectious Diseases (NIAID) [U01
AI034994]; NIAID; Eunice Kennedy Shriver National Institute of Child
Health and Human Development; National Cancer Institute; National
Institute on Drug Abuse; National Institute on Mental Health; National
Institute of Dental and Craniofacial Research; National Institute on
Alcohol Abuse and Alcoholism; National Institute on Deafness and other
Communication Disorders; NIH Office of Research on Women's Health; NIH
Clinical and Translation Science Award [UL1-TR000004]
FX This work was supported by the NIH and the National Institute of Allergy
and Infectious Diseases (NIAID) (through a subcontract of U01 AI034994
[to A. M. N. T.]). The WIHS is funded primarily by the NIAID, with
additional cofunding from the Eunice Kennedy Shriver National Institute
of Child Health and Human Development, the National Cancer Institute,
the National Institute on Drug Abuse, and the National Institute on
Mental Health. Targeted supplemental funding for specific projects is
also provided by the National Institute of Dental and Craniofacial
Research, the National Institute on Alcohol Abuse and Alcoholism, the
National Institute on Deafness and other Communication Disorders, and
the NIH Office of Research on Women's Health. WIHS data collection is
also supported by the NIH Clinical and Translation Science Award
UL1-TR000004 to the University of California-San Francisco.
NR 15
TC 5
Z9 5
U1 1
U2 3
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0022-1899
EI 1537-6613
J9 J INFECT DIS
JI J. Infect. Dis.
PD NOV 1
PY 2015
VL 212
IS 9
BP 1397
EP 1401
DI 10.1093/infdis/jiv233
PG 5
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA CW1QX
UT WOS:000364767500008
PM 25895986
ER
PT J
AU Gilbert, PB
Gabriel, EE
Hudgens, MG
Miao, XP
Li, XM
Su, SC
Parrino, J
Chan, ISF
AF Gilbert, Peter B.
Gabriel, Erin E.
Hudgens, Michael G.
Miao, Xiaopeng
Li, Xiaoming
Su, Shu-Chih
Parrino, Janie
Chan, Ivan S. F.
TI Ifit1 Protects Against Lipopolysaccharide and D-galactosamine-Induced
Fatal Hepatitis by Inhibiting Activation of the JNK Pathway Reply
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Letter
ID VACCINE; TRIALS
C1 [Gilbert, Peter B.] Univ Washington, Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, Seattle, WA 98195 USA.
[Gilbert, Peter B.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Li, Xiaoming] Gilead Sci Inc, Biostat, Seattle, WA USA.
[Gabriel, Erin E.] NIAID, Biostat Res Branch, Bethesda, MD 20892 USA.
[Hudgens, Michael G.] Univ N Carolina, Dept Biostat, Chapel Hill, NC 27515 USA.
[Miao, Xiaopeng] Biogen Inc, Biostat, Cambridge, MA 02142 USA.
[Su, Shu-Chih; Parrino, Janie; Chan, Ivan S. F.] Merck & Co Inc, Whitehouse Stn, NJ USA.
RP Gilbert, PB (reprint author), Fred Hutchinson Canc Res Ctr, Vaccine & Infect Dis Div, 1100 Fairview Ave N,POB 19024, Seattle, WA 98109 USA.
EM pgilbert@scharp.org
FU NIAID NIH HHS [UM1 AI068635]
NR 5
TC 0
Z9 0
U1 0
U2 1
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0022-1899
EI 1537-6613
J9 J INFECT DIS
JI J. Infect. Dis.
PD NOV 1
PY 2015
VL 212
IS 9
BP 1521
EP 1523
DI 10.1093/infdis/jiv287
PG 3
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA CW1QX
UT WOS:000364767500021
PM 25985906
ER
PT J
AU Moore, E
Tycko, R
AF Moore, Eric
Tycko, Robert
TI Micron-scale magnetic resonance imaging of both liquids and solids
SO JOURNAL OF MAGNETIC RESONANCE
LA English
DT Article
DE MRI; Solid state NMR; Lee-Goldburg decoupling; Constant-time imaging;
Microcoil
ID DYNAMIC NUCLEAR-POLARIZATION; VACANCY SPIN SENSOR; NMR MICROSCOPY; STATE
NMR; PULSE SEQUENCES; SINGLE-CELL; RESOLUTION; FIELD; SENSITIVITY;
NUTATION
AB We describe and demonstrate a novel apparatus for magnetic resonance imaging (MRI), suitable for imaging of both liquid and solid samples with micron-scale isotropic resolution. The apparatus includes a solenoidal radio-frequency microcoil with 170 mu m inner diameter and a set of planar gradient coils, all wound by hand and supported on a series of stacked sapphire plates. The design ensures efficient heat dissipation during gradient pulses and also facilitates disassembly, sample changes, and reassembly. To demonstrate liquid state H-1 MRI, we present an image of polystyrene beads within CuSO4-doped water, contained within a capillary tube with 100 mu m inner diameter, with 5.0 mu m isotropic resolution. To demonstrate solid state H-1 MRI, we present an image of NH4Cl particles within the capillary tube, with 8.0 mu m isotropic resolution. High-resolution solid state MRI is enabled by frequency-switched Lee-Goldburg decoupling, with an effective rotating frame field amplitude of 289 kHz. At room temperature, pulsed gradients of 4 T/m (i.e., 170 Hz/mu m for H-1 MRI) are achievable in all three directions with currents of 10 A or less. The apparatus is contained within a variable-temperature liquid helium cryostat, which will allow future efforts to obtain MRI images at low temperatures with signal enhancement by dynamic nuclear polarization. Published by Elsevier Inc.
C1 [Moore, Eric; Tycko, Robert] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
RP Tycko, R (reprint author), NIH, Bldg 5,Room 112, Bethesda, MD 20892 USA.
EM robertty@mail.nih.gov
FU Intramural Research Program of the National Institute of Diabetes and
Digestive and Kidney Diseases, a component of the National Institutes of
Health
FX This work was supported by the Intramural Research Program of the
National Institute of Diabetes and Digestive and Kidney Diseases, a
component of the National Institutes of Health.
NR 55
TC 1
Z9 1
U1 6
U2 29
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1090-7807
EI 1096-0856
J9 J MAGN RESON
JI J. Magn. Reson.
PD NOV
PY 2015
VL 260
BP 1
EP 9
DI 10.1016/j.jmr.2015.09.001
PG 9
WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical;
Spectroscopy
SC Biochemistry & Molecular Biology; Physics; Spectroscopy
GA CW4SK
UT WOS:000364982200001
PM 26397215
ER
PT J
AU Basheer, WA
Harris, BS
Mentrup, HL
Abreha, M
Thames, EL
Lea, JB
Swing, DA
Copeland, NG
Jenkins, NA
Price, RL
Matesic, LE
AF Basheer, Wassim A.
Harris, Brett S.
Mentrup, Heather L.
Abreha, Measho
Thames, Elizabeth L.
Lea, Jessica B.
Swing, Deborah A.
Copeland, Neal G.
Jenkins, Nancy A.
Price, Robert L.
Matesic, Lydia E.
TI Cardiomyocyte-specific overexpression of the ubiquitin ligase Wwp1
contributes to reduction in Connexin 43 and arrhythmogenesis
SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
LA English
DT Article
DE Connexin; Gap junction; Wwp1; Ubiquitin; Arrhythmogenesis
ID GAP-JUNCTION PROTEIN; POTENTIAL MOLECULAR TARGET; E3 LIGASE; ADULT-RAT;
HEART; CANCER; GROWTH; GENE; CONDUCTION; EXPRESSION
AB Gap junctions (GJ) are intercellular channels composed of connexin subunits that play a critical role in a diverse number of cellular processes in all tissue types. In the heart, GJs mediate electrical coupling between cardiomyocytes and display mislocalization and/or downregulation in cardiac disease (a process known as GJ remodeling), producing an arrhythmogenic substrate. The main constituent of GJs in the ventricular myocardium is Connexin 43 (Cx43), an integral membrane protein that is rapidly turned over and shows decreased expression or function with age. We hypothesized that Wwp1, an ubiquitin ligase whose expression in known to increase in aging-related pathologies, may regulate Cx43 in vivo by targeting it for ubiquitylation and degradation and yield tissue-specific Cx43 loss of function phenotypes. When Wwp1 was globally overexpressed in mice under the control of a beta-actin promoter, the highest induction of Wwp1 expression was observed in the heart which was associated with a 90% reduction in cardiac Cx43 protein levels, left ventricular hypertrophy (LVH), and the development of lethal ventricular arrhythmias around 8 weeks of age. This phenotype was completely penetrant in two independent founder lines. Cardiomyocyte-specific overexpression of Wwp1 confirmed that this phenotype was cell autonomous and delineated Cx43-dependent and independent roles for Wwp1 in arrhythmogenesis and LVH, respectively. Using a cell-based system, it was determined that Wwp1 co-immunoprecipitates with and ubiquitylates Cx43, causing a decrease in the steady state levels of Cx43 protein. These findings offer new mechanistic insights into the regulation of Cx43 which may be exploitable in various gap junctionopathies. (C) 2015 Elsevier Ltd. All rights reserved.
C1 [Basheer, Wassim A.; Mentrup, Heather L.; Abreha, Measho; Thames, Elizabeth L.; Lea, Jessica B.; Matesic, Lydia E.] Univ S Carolina, Dept Biol Sci, Columbia, SC 29208 USA.
[Harris, Brett S.] Med Univ S Carolina, Dept Regenerat Med & Cell Biol, Charleston, SC 29425 USA.
[Swing, Deborah A.; Copeland, Neal G.; Jenkins, Nancy A.] NCI, Mouse Canc Genet Program, Frederick, MD 21702 USA.
[Price, Robert L.] Univ S Carolina, Sch Med, Dept Cell Biol & Anat, Columbia, SC 29209 USA.
RP Matesic, LE (reprint author), 715 Sumter St, Columbia, SC 29208 USA.
EM lmatesic@biol.sc.edu
FU National Institutes of Health [R01HL104030]; American Heart Association
[10SDG2650005]; intramural research program of the National Institutes
of Health, National Cancer Institute, Center for Cancer Research
FX This work was supported by the National Institutes of Health
[R01HL104030 to L.E.M.], the American Heart Association [10SDG2650005 to
L.E.M.], and the intramural research program of the National Institutes
of Health, National Cancer Institute, Center for Cancer Research [N.G.C.
and N.A.J.].
NR 53
TC 5
Z9 5
U1 2
U2 6
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0022-2828
EI 1095-8584
J9 J MOL CELL CARDIOL
JI J. Mol. Cell. Cardiol.
PD NOV
PY 2015
VL 88
BP 1
EP 13
DI 10.1016/j.yjmcc.2015.09.004
PG 13
WC Cardiac & Cardiovascular Systems; Cell Biology
SC Cardiovascular System & Cardiology; Cell Biology
GA CW5TK
UT WOS:000365059300001
PM 26386426
ER
PT J
AU Boylston, JA
Sun, JH
Chen, Y
Gucek, M
Sack, MN
Murphy, E
AF Boylston, Jennifer A.
Sun, Junhui
Chen, Yong
Gucek, Marjan
Sack, Michael N.
Murphy, Elizabeth
TI Characterization of the cardiac succinylome and its role in
ischemia-reperfusion injury
SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
LA English
DT Article
DE Sirt5; Ischemia-reperfusion; Cardiac; Succinylation; Succinate
ID LYSINE SUCCINYLATION; POSTTRANSLATIONAL MODIFICATION; PROTEIN;
ACETYLATION; SIRT5; DEGRADATION; CARDIOMYOCYTES; IDENTIFICATION;
PROTEASOME; TURNOVER
AB Succinylation refers to modification of lysine residues with succinyl groups donated by succinyl-CoA. Sirtuin5 (Sirt5) is a mitochondrial NAD(+)-dependent deacylase that catalyzes the removal of succinyl groups from proteins. Sirt5 and protein succinylation are conserved across species, suggesting functional importance of the modification. Sirt5 loss impacts liver metabolism but the role of succinylation in the heart has not been explored. We combined affinity enrichment with proteomics and mass spectrometry to analyze total succinylated lysine content of mitochondria isolated from WT and Sirt5(-/-) mouse hearts. We identified 887 succinylated lysine residues in 184 proteins. 44 peptides (5 proteins) occurred uniquely in WT samples, 289 (46 proteins) in Sirt5(-/-) samples, and 554 (133 proteins) were common to both groups. The 46 unique proteins in Sirt5(-/-) heart participate in metabolic processes such as fatty add beta-oxidation (Eci2) and branched chain amino acid catabolism, and include respiratory chain proteins (Ndufa7, 12, 13, Dhsa). We performed label-free analysis of the peptides common to WT and Sirt5(-/-) hearts. 16 peptides from 9 proteins were significantly increased in Sirt5(-/-) by at least 30%. The adenine nucleotide transporter 1 showed the highest increase in succinylation in Sirt5(-/-) (108.4 fold). The data indicate that succinylation is widespread in the heart and enriched in metabolic pathways. We examined whether the loss of Sirt5 would impact ischemia-reperfusion (I/R) injury and we found an increase in infarct size in Sirt5(-/-) hearts compared to WT littermates (68.5(+)/_ 1.1% Sirt5(-/-) vs 39.6(+)/(-) 6.8% WT) following 20 min of ischemia and 90-min reperfusion. We further demonstrate that I/R injury in Sirt5(-/-) heart is restored to WT levels by pretreatment with dimethyl malonate, a competitive inhibitor of succinate dehydrogenase (SDH), implicating alteration in SDEI activity as causative of the injury. Published by Elsevier Ltd.
C1 [Boylston, Jennifer A.; Sun, Junhui; Murphy, Elizabeth] NHLBI, Syst Biol Ctr, NIH, Bethesda, MD USA.
[Chen, Yong; Gucek, Marjan] NHLBI, Prote Core Facil, NIH, Bethesda, MD 20892 USA.
[Sack, Michael N.] NHLBI, Ctr Mol Med, NIH, Bethesda, MD 20892 USA.
RP Murphy, E (reprint author), NHLBI, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA.
EM murphy1@nhlbi.nih.gov
FU National Heart, Lung, and Blood Institute (NHLBI) [ZIA HL002066]
FX This work was funded by the National Heart, Lung, and Blood Institute
(NHLBI) Intramural Program (ZIA HL002066). We thank Dr. Christian Combs
and the NHLBI Light Microscopy Core for their assistance with the Mito
Sox measurements.
NR 30
TC 11
Z9 11
U1 3
U2 9
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0022-2828
EI 1095-8584
J9 J MOL CELL CARDIOL
JI J. Mol. Cell. Cardiol.
PD NOV
PY 2015
VL 88
BP 73
EP 81
DI 10.1016/j.yjmcc.2015.09.005
PG 9
WC Cardiac & Cardiovascular Systems; Cell Biology
SC Cardiovascular System & Cardiology; Cell Biology
GA CW5TK
UT WOS:000365059300007
PM 26388266
ER
PT J
AU Farber, A
Tan, TW
Hu, B
Dember, LM
Beck, GJ
Dixon, BS
Kusek, JW
Feldman, HI
AF Farber, Alik
Tan, Tze-Woei
Hu, Bo
Dember, Laura M.
Beck, Gerald J.
Dixon, Bradley S.
Kusek, John W.
Feldman, Harold I.
CA DAC Study Grp
TI The effect of location and configuration on forearm and upper arm
hemodialysis arteriovenous grafts
SO JOURNAL OF VASCULAR SURGERY
LA English
DT Article
ID TRANSPOSED BRACHIOBASILIC FISTULAS; VASCULAR ACCESS; BRACHIOCEPHALIC
FISTULAS; RANDOMIZED MULTICENTER; DIALYSIS-ACCESS; CLINICAL-TRIAL; LOOP;
PATENCY; POLYTETRAFLUOROETHYLENE; SURVIVAL
AB Objective: The arteriovenous graft (AVG) is most often used in hemodialysis patients when an autogenous fistula is not feasible. The optimal location (forearm or upper arm) and configuration (loop or straight) of AVGs are not known. To evaluate relationships of AVG location and configuration with patency, we conducted a secondary analysis using data from a randomized, placebo-controlled trial of dipyridamole plus aspirin for newly placed AVG.
Methods: Participants of the Dialysis Access Consortium (DAC) Graft Study with newly placed upper extremity prosthetic grafts involving the brachial artery were studied. Multivariable analyses adjusting for trial treatment group, center, gender, race, body mass index, diabetes, current treatment with chronic dialysis, and prior arteriovenous vascular access or central venous catheter were performed to compare outcomes of forearm (fAVG) and upper arm (uAVG) grafts, including loss of primary unassisted patency (LPUP) and cumulative primary graft failure (CGF). Subgroup analyses of graft configuration and outflow vein used were also conducted.
Results: A total of 508 of the 649 participants (78%) enrolled in the trial had an upper extremity brachial artery graft placed, 255 with fAVG and 253 with uAVG. Participants with fAVG were less often male (33% vs 43%; P=. 03), African American (62% vs 78%; P <.001), and receiving dialysis at the time of surgery (62% vs 80%; P <.001). Participants with fAVG had a higher mean body mass index (33 vs 29; P <.001). The LPUP (fAVG 70% vs uAVG 78%; P =. 07) and CGF (33% vs 36%; P =.91) were similar between fAVG and uAVG at 1-year follow-up. In multivariable analysis, AVG location (uAVG vs fAVG) was not associated with LPUP (hazard ratio, 1.21; 95% confidence interval, 0.90-1.63; P =.20) or CGF (hazard ratio, 1.36; 95% confidence interval, 0.94-1.97; P =.10). LPUP did not differ significantly between fAVG and uAVG among subgroups based on AVG configuration (P = 1.00) or outflow vein used (P =.16).
Conclusions: Patency was comparable between fAVG and uAVG despite the larger caliber veins often encountered in the upper arm in carefully selected patients. Our findings support the traditional view that, in order to preserve a maximal number of access sites, the forearm location should be considered first before resorting to an upper arm graft.
C1 [Farber, Alik] Boston Univ, Med Ctr, Div Vasc & Endovasc Surg, Boston, MA USA.
[Tan, Tze-Woei] Louisiana State Univ, Shreveport Hlth Sci Ctr, Div Vasc Surg, Shreveport, LA 71105 USA.
[Hu, Bo; Beck, Gerald J.] Cleveland Clin, Dept Quantitat Hlth Sci, Cleveland, OH 44106 USA.
[Dember, Laura M.; Feldman, Harold I.] Univ Penn, Perelman Sch Med, Renal Electrolyte & Hypertens Div, Philadelphia, PA 19104 USA.
[Feldman, Harold I.] Univ Penn, Perelman Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA.
[Dixon, Bradley S.] Univ Iowa, Nephrol Sect, Iowa City, IA USA.
[Kusek, John W.] NIDDK, NIH, Bethesda, MD 20892 USA.
RP Farber, A (reprint author), Boston Med Ctr, Div Vasc & Endovasc Surg, 88 E Newton St,Collamore 5,Ste D506, Boston, MA 02118 USA.
EM alik.farber@bmc.org
NR 43
TC 1
Z9 1
U1 0
U2 3
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0741-5214
J9 J VASC SURG
JI J. Vasc. Surg.
PD NOV
PY 2015
VL 62
IS 5
BP 1258
EP 1264
DI 10.1016/j.jvs.2015.06.132
PG 7
WC Surgery; Peripheral Vascular Disease
SC Surgery; Cardiovascular System & Cardiology
GA CW8IF
UT WOS:000365242000022
PM 26254823
ER
PT J
AU Fabbri, E
An, Y
Schrack, JA
Gonzalez-Freire, M
Zoli, M
Simonsick, EM
Guralnik, JM
Boyd, CM
Studenski, SA
Ferrucci, L
AF Fabbri, Elisa
An, Yang
Schrack, Jennifer A.
Gonzalez-Freire, Marta
Zoli, Marco
Simonsick, Eleanor M.
Guralnik, Jack M.
Boyd, Cynthia M.
Studenski, Stephanie A.
Ferrucci, Luigi
TI Energy Metabolism and the Burden of Multimorbidity in Older Adults:
Results From the Baltimore Longitudinal Study of Aging
SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL
SCIENCES
LA English
DT Article
DE Multimorbidity; Resting metabolic rate; Aging; Health status; Metabolism
ID X-RAY ABSORPTIOMETRY; BODY-COMPOSITION; INDIRECT CALORIMETRY; HEALTH;
EXPENDITURE; LIFE; POPULATION; LONGEVITY; CACHEXIA; WEIGHT
AB Excessively elevated resting metabolic rate ( RMR) for persons of a certain age, sex, and body composition is a mortality risk factor. Whether elevated RMR constitutes an early marker of health deterioration in older adult has not been fully investigated. Using data from the Baltimore Longitudinal Study of Aging, we hypothesized that higher RMR ( i) was cross-sectionally associated with higher multimorbidity and ( ii) predicted higher multimorbidity in subsequent follow-ups. The analysis included 695 Baltimore Longitudinal Study of Aging participants, aged 60 or older at baseline, of whom 248 had follow-up data available 2 years later and 109 four years later. Multimorbidity was assessed as number of chronic diseases. RMR was measured by indirect calorimetry and was tested in regression analyses adjusted for covariates age, sex, and dual-energy x-ray absorptiometrymeasured total body fat mass and lean mass. Baseline RMR and multimorbidity were positively associated, independent of covariates ( p =.002). Moreover, in a three-wave bivariate autoregressive cross-lagged model adjusted for covariates, higher prior RMR predicted greater future multimorbidity above and beyond the cross-sectional and autoregressive associations ( p = .034). RMR higher than expected, given age, sex, and body composition, predicts future higher multimorbidity in older adults and may be used as early biomarker of impending health deterioration. Replication and the development of normative data are required for clinical translation.
C1 [Fabbri, Elisa; An, Yang; Schrack, Jennifer A.; Gonzalez-Freire, Marta; Simonsick, Eleanor M.; Studenski, Stephanie A.; Ferrucci, Luigi] NIA, Intramural Res Branch, NIH, Baltimore, MD 21224 USA.
[Fabbri, Elisa; Zoli, Marco] Univ Bologna, Dept Med & Surg Sci, I-40126 Bologna, Italy.
[Schrack, Jennifer A.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Guralnik, Jack M.] Univ Maryland, Sch Med, Dept Epidemiol & Publ Hlth, Baltimore, MD 21201 USA.
[Boyd, Cynthia M.] Johns Hopkins Sch Med, Div Geriatr Med & Gerontol, Dept Med, Baltimore, MD USA.
RP Fabbri, E (reprint author), NIA, Intramural Res Branch, NIH, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM elisa.fabbri@nih.gov
FU Intramural Research Program of National Institutes of Health, National
Institute on Aging [03-AG-0325]; Paul Beeson Career Development Award
Program [NIA K23 AG032910]; Paul Beeson Career Development Award Program
(AFAR); Paul Beeson Career Development Award Program (John A. Hartford
Foundation); Paul Beeson Career Development Award Program (Atlantic
Philanthropies); Paul Beeson Career Development Award Program (Starr
Foundation)
FX This research was supported by the Intramural Research Program of
National Institutes of Health, National Institute on Aging (03-AG-0325).
Data for these analyses were obtained from the Baltimore Longitudinal
Study of Aging, a study performed by the National Institute on Aging.
Dr. C.M.B. was supported by the Paul Beeson Career Development Award
Program (NIA K23 AG032910, AFAR, The John A. Hartford Foundation, The
Atlantic Philanthropies, The Starr Foundation, and an anonymous donor).
NR 38
TC 12
Z9 12
U1 2
U2 5
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1079-5006
EI 1758-535X
J9 J GERONTOL A-BIOL
JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci.
PD NOV
PY 2015
VL 70
IS 11
BP 1297
EP 1303
DI 10.1093/gerona/glu209
PG 7
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA CW1QF
UT WOS:000364765700001
PM 25409892
ER
PT J
AU Kritchevsky, SB
de Cabo, R
AF Kritchevsky, Stephen B.
de Cabo, Rafael
TI Energy - A Hallmark of Physical Function
SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL
SCIENCES
LA English
DT Editorial Material
C1 [Kritchevsky, Stephen B.] Wake Forest Sch Med, Sticht Ctr Aging, Winston Salem, NC 27157 USA.
[de Cabo, Rafael] NIA, Expt Gerontol Sect, Baltimore, MD 21224 USA.
RP Kritchevsky, SB (reprint author), Wake Forest Sch Med, Sticht Ctr Aging, Med Ctr Blvd, Winston Salem, NC 27157 USA.
EM skritche@wakehealth.edu
RI de Cabo, Rafael/J-5230-2016;
OI de Cabo, Rafael/0000-0002-3354-2442; , rafael/0000-0003-2830-5693
NR 1
TC 1
Z9 1
U1 0
U2 2
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1079-5006
EI 1758-535X
J9 J GERONTOL A-BIOL
JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci.
PD NOV
PY 2015
VL 70
IS 11
BP 1333
EP 1333
DI 10.1093/gerona/glv131
PG 1
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA CW1QF
UT WOS:000364765700005
PM 26273026
ER
PT J
AU Gonzalez-Freire, M
de Cabo, R
Bernier, M
Sollott, SJ
Fabbri, E
Navas, P
Ferrucci, L
AF Gonzalez-Freire, Marta
de Cabo, Rafael
Bernier, Michel
Sollott, Steven J.
Fabbri, Elisa
Navas, Placido
Ferrucci, Luigi
TI Reconsidering the Role of Mitochondria in Aging
SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL
SCIENCES
LA English
DT Article
DE Mitochondria; Aging; Lifespan
ID FATTY-ACID UNSATURATION; SKELETAL-MUSCLE MITOCHONDRIA; OXIDATIVE STRESS;
ELECTRON-TRANSPORT; DELETION MUTATIONS; LON PROTEASE; LIFE-SPAN;
PERMEABILITY TRANSITION; ENDOPLASMIC-RETICULUM; AEROBIC CAPACITY
AB Background: Mitochondrial dysfunction has long been considered a major contributor to aging and age-related diseases. Harman's Mitochondrial Free Radical Theory of Aging postulated that somatic mitochondrial DNA mutations that accumulate over the life span cause excessive production of reactive oxygen species that damage macromolecules and impair cell and tissue function. Indeed, studies have shown that maximal oxidative capacity declines with age while reactive oxygen species production increases. Harman's hypothesis has been seriously challenged by recent studies showing that reactive oxygen species evoke metabolic health and longevity, perhaps through hormetic mechanisms that include autophagy. The purpose of this review is to scan the ever-growing literature on mitochondria from the perspective of aging research and try to identify priority questions that should be addressed in future research.Methods: A systematic search of peer-reviewed studies was performed using PubMed. Search terms included (i) mitochondria or mitochondrial; (ii) aging, ageing, older adults or elderly; and (iii) reactive oxygen species, mitochondria dynamics, mitochondrial proteostasis, cytosol, mitochondrial-associated membranes, redox homeostasis, electron transport chain, electron transport chain efficiency, epigenetic regulation, DNA heteroplasmy.Results: The importance of mitochondrial biology as a trait d'union between the basic biology of aging and the pathogenesis of age-related diseases is stronger than ever, although the emphasis has moved from reactive oxygen species production to other aspects of mitochondrial physiology, including mitochondrial biogenesis and turnover, energy sensing, apoptosis, senescence, and calcium dynamics. Conclusions: Mitochondria could play a key role in the pathophysiology of aging or in the earlier stages of some events that lead to the aging phenotype. Therefore, mitochondria will increasingly be targeted to prevent and treat chronic diseases and to promote healthy aging.
C1 [Gonzalez-Freire, Marta; de Cabo, Rafael; Bernier, Michel; Fabbri, Elisa; Ferrucci, Luigi] NIA, Translat Gerontol Branch, NIH, Baltimore, MD 21224 USA.
[Sollott, Steven J.] NIA, Lab Cardiovasc Sci, NIH, Baltimore, MD 21224 USA.
[Fabbri, Elisa] Univ Bologna, Dept Med & Surg Sci, I-40126 Bologna, Italy.
[Navas, Placido] Univ Pablo de Olavide, CSIC, Inst Salud Carlos 3, Ctr Andaluz Biol Desarrollo,CIBERER, Seville 41013, Spain.
RP Gonzalez-Freire, M (reprint author), NIA, NIH, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM marta.gonzalezfreire@nih.gov
RI de Cabo, Rafael/J-5230-2016;
OI de Cabo, Rafael/0000-0002-3354-2442; , rafael/0000-0003-2830-5693
FU Intramural Research Program of NIH, National Institute on Aging
FX This research was supported by the Intramural Research Program of NIH,
National Institute on Aging.
NR 101
TC 24
Z9 24
U1 18
U2 60
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1079-5006
EI 1758-535X
J9 J GERONTOL A-BIOL
JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci.
PD NOV
PY 2015
VL 70
IS 11
BP 1334
EP 1342
DI 10.1093/gerona/glv070
PG 9
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA CW1QF
UT WOS:000364765700006
PM 25995290
ER
PT J
AU Santanasto, AJ
Glynn, NW
Jubrias, SA
Conley, KE
Boudreau, RM
Amati, F
Mackey, DC
Simonsick, EM
Strotmeyer, ES
Coen, PM
Goodpaster, BH
Newman, AB
AF Santanasto, Adam J.
Glynn, Nancy W.
Jubrias, Sharon A.
Conley, Kevin E.
Boudreau, Robert M.
Amati, Francesca
Mackey, Dawn C.
Simonsick, Eleanor M.
Strotmeyer, Elsa S.
Coen, Paul M.
Goodpaster, Bret H.
Newman, Anne B.
TI Skeletal Muscle Mitochondrial Function and Fatigability in Older Adults
SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL
SCIENCES
LA English
DT Article
DE Mitochondrial function; Fatigability; Aerobic capacity; Skeletal muscle
ID OXIDATIVE CAPACITY; EXERCISE INTOLERANCE; AEROBIC CAPACITY; FATIGUE;
AGE; DECLINE; ASSOCIATION; PERFORMANCE; DISABILITY; ENERGETICS
AB Background. Fatigability increases while the capacity for mitochondrial energy production tends to decrease significantly with age. Thus, diminished mitochondrial function may contribute to higher levels of fatigability in older adults. Methods. The relationship between fatigability and skeletal muscle mitochondrial function was examined in 30 participants aged 78.5 +/- 5.0 years ( 47% female, 93% white), with a body mass index of 25.9 +/- 2.7 kg/ m(2) and usual gait-speed of 1.2 +/- 0.2 m/s. Fatigability was defined using rating of perceived exertion ( 6-20 point Borg scale) after a 5-minute treadmill walk at 0.72 m/s. Phosphocreatine recovery in the quadriceps was measured using P-31 magnetic resonance spectroscopy and images of the quadriceps were captured to calculate quadriceps volume. ATPmax ( mM ATP/s) and oxidative capacity of the quadriceps ( ATPmax center dot Quadriceps volume) were calculated. Peak aerobic capacity ( VO2 peak) was measured using a modified Balke protocol. Results. ATPmax center dot Quadriceps volume was associated with VO2 peak and was 162.61 mM ATP center dot mL/s lower ( p =.03) in those with high ( rating of perceived exertion >= 10) versus low ( rating of perceived exertion <= 9) fatigability. Participants with high fatigability required a significantly higher proportion of VO 2 peak to walk at 0.72 m/s compared with those with low fatigability ( 58.7 +/- 19.4% vs 44.9 +/- 13.2%, p <.05). After adjustment for age and sex, higher ATPmax was associated with lower odds of having high fatigability ( odds ratio: 0.34, 95% CI: 0.11- 1.01, p =.05).
C1 [Santanasto, Adam J.; Glynn, Nancy W.; Boudreau, Robert M.; Strotmeyer, Elsa S.; Newman, Anne B.] Univ Pittsburgh, Grad Sch Publ Hlth, Ctr Aging & Populat Hlth, Dept Epidemiol, Pittsburgh, PA 15260 USA.
[Amati, Francesca; Coen, Paul M.; Goodpaster, Bret H.] Univ Pittsburgh, Sch Med, Div Endocrinol & Metab, Pittsburgh, PA 15260 USA.
[Jubrias, Sharon A.; Conley, Kevin E.] Univ Washington, Translat Ctr Metab Imaging, Seattle, WA 98195 USA.
[Mackey, Dawn C.] Simon Fraser Univ, Dept Biomed Physiol & Kinesiol, Burnaby, BC V5A 1S6, Canada.
[Simonsick, Eleanor M.] NIA, Translat Gerontol Branch, Baltimore, MD 21224 USA.
[Coen, Paul M.] Univ Pittsburgh, Sch Educ, Dept Hlth & Phys Act, Pittsburgh, PA 15260 USA.
RP Glynn, NW (reprint author), 130 DeSoto St,A531 Crabtree Hall, Pittsburgh, PA 15261 USA.
EM glynnn@edc.pitt.edu
RI Newman, Anne/C-6408-2013;
OI Newman, Anne/0000-0002-0106-1150; Strotmeyer, Elsa/0000-0002-4093-6036;
Boudreau, Robert/0000-0003-0162-5187; Amati,
Francesca/0000-0002-1731-0262; Coen, Paul/0000-0002-2805-2115; Glynn,
Nancy/0000-0003-2265-0162
FU National Institute on Aging at the National Institutes of Health
[1RC2AG036594-01, 1RC2AG036606]
FX This work was supported by the National Institute on Aging at the
National Institutes of Health (1RC2AG036594-01 and 1RC2AG036606)
NR 39
TC 11
Z9 11
U1 1
U2 6
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1079-5006
EI 1758-535X
J9 J GERONTOL A-BIOL
JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci.
PD NOV
PY 2015
VL 70
IS 11
BP 1379
EP 1385
DI 10.1093/gerona/glu134
PG 7
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA CW1QF
UT WOS:000364765700011
PM 25167867
ER
PT J
AU Katzman, SM
Strotmeyer, ES
Nalls, MA
Zhao, YQ
Mooney, S
Schork, N
Newman, AB
Harris, TB
Yaffe, K
Cummings, SR
Liu, YM
Tranah, GJ
AF Katzman, Shana M.
Strotmeyer, Elsa S.
Nalls, Michael A.
Zhao, Yiqiang
Mooney, Sean
Schork, Nik
Newman, Anne B.
Harris, Tamara B.
Yaffe, Kristine
Cummings, Steven R.
Liu, Yongmei
Tranah, Gregory J.
CA Hlth Aging Body Composition Study
TI Mitochondrial DNA Sequence Variation Associated With Peripheral Nerve
Function in the Elderly
SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL
SCIENCES
LA English
DT Article
DE Sensory; Genetics; Epidemiology; Functional Performance
ID AMYLOID PRECURSOR PROTEIN; CYCLIC VOMITING SYNDROME; ALZHEIMERS-DISEASE;
BODY-COMPOSITION; CALORIE RESTRICTION; MUTATIONAL ANALYSIS;
ENERGY-EXPENDITURE; DIABETES-MELLITUS; POLG MUTATIONS; RETT-SYNDROME
AB Background. Mitochondrial dysfunction is a prominent hallmark of many sensory neuropathies. The purpose of this study was to assess the influence of mitochondrial DNA sequence variation on peripheral nerve function in the population-based Health, Aging, and Body Composition Study. Methods. We investigated the role of common mitochondrial DNA variation ( n = 1,580) and complete mitochondrial DNA sequences ( n = 138) on peroneal motor nerve conduction velocity and amplitude, average vibration detection threshold, and monofilament sensitivity. Results. Nominal associations among common mitochondrial DNA variants and haplogroups were identified but were not statistically significant after adjustment for multiple comparisons. Sequence-based approaches were used to identify aggregate variant associations across the 16S rRNA ( weighted- sum, p = 2E-05 and variable threshold, p = 9E-06) for nerve conduction velocity. Several of these rare 16S variants occurred at or near sites with earlier disease associations and are also in close proximity to the peptidyl transferase center, which is the catalytic center of the 16S rRNA Conclusions. These results suggest that sequence variation related to mitochondrial protein synthesis/ assembly is associated with peripheral nerve function and may provide insight into targets for intervention or new clinical strategies to preserve nerve function in late life.
C1 [Katzman, Shana M.] Univ Calif San Francisco, Dept Innovat Technol & Alliances, San Francisco, CA 94143 USA.
[Strotmeyer, Elsa S.; Newman, Anne B.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15260 USA.
[Nalls, Michael A.] NIA, Neurogenet Lab, Intramural Res Program, Bethesda, MD 20892 USA.
[Zhao, Yiqiang] China Agr Univ, State Key Lab Agrobiotechnol, Beijing 100094, Peoples R China.
[Mooney, Sean] Buck Inst Res Aging, Dept Bioinformat, Novato, CA USA.
[Schork, Nik] J Craig Venter Inst, Dept Human Biol, La Jolla, CA USA.
[Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
[Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA.
[Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA.
[Yaffe, Kristine] Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94143 USA.
[Yaffe, Kristine] San Francisco VA Med Ctr, Dept Geriatr Psychiat, San Francisco, CA USA.
[Cummings, Steven R.; Tranah, Gregory J.] Calif Pacific Med Ctr, Res Inst, San Francisco, CA USA.
[Liu, Yongmei] Wake Forest Sch Med, Div Publ Hlth Sci, Winston Salem, NC USA.
RP Tranah, GJ (reprint author), UCSF, San Francisco Coordinating Ctr, Calif Pacific Med Ctr, Res Inst, 185 Berry St,Lobby 5,Suite 5700, San Francisco, CA 94107 USA.
EM gtranah@sfcc-cpmc.edu
RI Newman, Anne/C-6408-2013;
OI Newman, Anne/0000-0002-0106-1150; Strotmeyer, Elsa/0000-0002-4093-6036
FU National Institute on Aging (NIA) [N01-AG-6-2101, N01-AG-6-2103,
N01-AG-6-2106]; NIA [R01-AG028050, R01-AG032098, R03-AG032498]; NINR
[R01-NR012459, Z01A6000932]; National Institutes of Health
[HHSN268200782096C]; NLM [LM009722]; NIH, National Institute on Aging
FX This research was supported by National Institute on Aging (NIA)
contracts N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106; NIA grants
R01-AG028050, R01-AG032098, and R03-AG032498; NINR grant R01-NR012459
and Z01A6000932. Genotyping services were provided by the Center for
Inherited Disease Research (CIDR). CIDR is fully funded through a
federal contract from the National Institutes of Health to The Johns
Hopkins University, contract number HHSN268200782096C. Y.Z. was
supported by NLM grant LM009722. This research was supported in part by
the Intramural Research Program of the NIH, National Institute on Aging.
NR 85
TC 1
Z9 1
U1 2
U2 4
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1079-5006
EI 1758-535X
J9 J GERONTOL A-BIOL
JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci.
PD NOV
PY 2015
VL 70
IS 11
BP 1400
EP 1408
DI 10.1093/gerona/glu175
PG 9
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA CW1QF
UT WOS:000364765700014
PM 25394619
ER
PT J
AU Burkle, A
Grune, T
Gonos, ES
Bohr, VA
AF Buerkle, Alexander
Grune, Tilman
Gonos, Efstathios S.
Bohr, Vilhelm A.
TI Special Issue Biomarkers of Human Ageing
SO MECHANISMS OF AGEING AND DEVELOPMENT
LA English
DT Editorial Material
C1 [Buerkle, Alexander] Univ Konstanz, Dept Biol, D-78457 Constance, Germany.
[Grune, Tilman] German Inst Nutr Potsdam Rehbruecke DIfE, D-14558 Nuthetal, Germany.
[Gonos, Efstathios S.] Natl Hellen Res Fdn, Inst Biol Med Chem & Biotechnol, Athens 11635, Greece.
[Bohr, Vilhelm A.] NIA, Dept Mol Gerontol, Baltimore, MD 21224 USA.
RP Burkle, A (reprint author), Univ Konstanz, Dept Biol, D-78457 Constance, Germany.
EM alexander.buerkle@uni-konstanz.de
FU Intramural NIH HHS [Z01 AG000726-15]
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0047-6374
J9 MECH AGEING DEV
JI Mech. Ageing Dev.
PD NOV
PY 2015
VL 151
SI SI
BP 1
EP 1
DI 10.1016/j.mad.2015.08.008
PG 1
WC Cell Biology; Geriatrics & Gerontology
SC Cell Biology; Geriatrics & Gerontology
GA CX0CH
UT WOS:000365364000001
PM 26348899
ER
PT J
AU Lynn, GM
Laga, R
Darrah, PA
Ishizuka, AS
Balaci, AJ
Dulcey, AE
Pechar, M
Pola, R
Gerner, MY
Yamamoto, A
Buechler, CR
Quinn, KM
Smelkinson, MG
Vanek, O
Cawood, R
Hills, T
Vasalatiy, O
Kastenmuller, K
Francica, JR
Stutts, L
Tom, JK
Ryu, KA
Esser-Kahn, AP
Etrych, T
Fisher, KD
Seymour, LW
Seder, RA
AF Lynn, Geoffrey M.
Laga, Richard
Darrah, Patricia A.
Ishizuka, Andrew S.
Balaci, Alexandra J.
Dulcey, Andres E.
Pechar, Michal
Pola, Robert
Gerner, Michael Y.
Yamamoto, Ayako
Buechler, Connor R.
Quinn, Kylie M.
Smelkinson, Margery G.
Vanek, Ondrej
Cawood, Ryan
Hills, Thomas
Vasalatiy, Olga
Kastenmueller, Kathrin
Francica, Joseph R.
Stutts, Lalisa
Tom, Janine K.
Ryu, Keun Ah
Esser-Kahn, Aaron P.
Etrych, Tomas
Fisher, Kerry D.
Seymour, Leonard W.
Seder, Robert A.
TI In vivo characterization of the physicochemical properties of
polymer-linked TLR agonists that enhance vaccine immunogenicity
SO NATURE BIOTECHNOLOGY
LA English
DT Article
ID T-CELL IMMUNITY; DENDRITIC CELLS; INNATE IMMUNITY; LYMPH-NODES;
ADJUVANT; RESPONSES; ANTIGEN; PROTECTION; ACTIVATION; COPOLYMERS
AB The efficacy of vaccine adjuvants such as Toll-like receptor agonists (TLRa) can be improved through formulation and delivery approaches. Here, we attached small molecule TLR-7/8a to polymer scaffolds (polymer-TLR-7/8a) and evaluated how different physicochemical properties of the TLR-7/8a and polymer carrier influenced the location, magnitude and duration of innate immune activation in vivo. Particle formation by polymer-TLR-7/8a was the most important factor for restricting adjuvant distribution and prolonging activity in draining lymph nodes. The improved pharmacokinetic profile by particulate polymer-TLR-7/8a was also associated with reduced morbidity and enhanced vaccine immunogenicity for inducing antibodies and T cell immunity. We extended these findings to the development of a modular approach in which protein antigens are site-specifically linked to temperature-responsive polymer-TLR-7/8a adjuvants that self-assemble into immunogenic particles at physiologic temperatures in vivo. Our findings provide a chemical and structural basis for optimizing adjuvant design to elicit broad-based antibody and T cell responses with protein antigens.
C1 [Lynn, Geoffrey M.; Darrah, Patricia A.; Ishizuka, Andrew S.; Balaci, Alexandra J.; Yamamoto, Ayako; Buechler, Connor R.; Quinn, Kylie M.; Kastenmueller, Kathrin; Francica, Joseph R.; Seder, Robert A.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Lynn, Geoffrey M.; Laga, Richard; Cawood, Ryan; Hills, Thomas; Fisher, Kerry D.; Seymour, Leonard W.] Univ Oxford, Dept Oncol, Oxford, England.
[Laga, Richard; Pechar, Michal; Pola, Robert; Etrych, Tomas] Acad Sci Czech Republic, Inst Macromol Chem, Prague, Czech Republic.
[Dulcey, Andres E.; Vasalatiy, Olga] NHLBI, Imaging Probe Dev Ctr, NIH, Rockville, MD USA.
[Gerner, Michael Y.] NIAID, Lymphocyte Biol Sect, Lab Syst Biol, NIH, Bethesda, MD 20892 USA.
[Smelkinson, Margery G.] NIAID, Biol Imaging Sect, Res Technol Branch, NIH, Bethesda, MD 20892 USA.
[Vanek, Ondrej] Charles Univ Prague, Fac Sci, Dept Biochem, Prague, Czech Republic.
[Stutts, Lalisa; Tom, Janine K.; Ryu, Keun Ah; Esser-Kahn, Aaron P.] Univ Calif Irvine, Dept Chem, Irvine, CA 92717 USA.
RP Seder, RA (reprint author), NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM rseder@mail.nih.gov
RI Pechar, Michal/G-6423-2014; Laga, Richard/G-3627-2014; Etrych,
Tomas/G-3420-2014; Pola, Robert/G-5723-2014; Vanek, Ondrej/I-7022-2016;
OI Etrych, Tomas/0000-0001-5908-5182; Vanek, Ondrej/0000-0003-1190-8535;
Ishizuka, Andrew/0000-0002-3024-7536
FU BIOPOL project (Ministry of Education, Youth and Sports of the Czech
Republic) [EE2.3.30.0029]; Czech Science Foundation [15-15181S]; Charles
University [UNCE 204025/2012]; Cancer Research UK [C552/A17720]; Office
of AIDS Research of the US National Institutes of Health; National
Institute of Allergy and Infectious Diseases of the US National
Institutes of Health
FX The authors wish to acknowledge M. Dillon, K. Wuddie and C. Chiedi at
the Vaccine Research Center and B. Klaunberg and V. Diaz at the Mouse
Imaging Facility (MIF) for their valuable support and assistance with
the animal studies. We would also like to thank K. Ulbrich, R. Swenson
and G. Griffiths for their support and helpful insights. This work was
supported in part by the BIOPOL project (Grant of the Ministry of
Education, Youth and Sports of the Czech Republic, no. EE2.3.30.0029);
by the Czech Science Foundation (15-15181S); by Charles University (UNCE
204025/2012); by a Cancer Research UK grant (C552/A17720); and by the
Office of AIDS Research and the National Institute of Allergy and
Infectious Diseases of the US National Institutes of Health.
NR 58
TC 25
Z9 26
U1 21
U2 63
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1087-0156
EI 1546-1696
J9 NAT BIOTECHNOL
JI Nat. Biotechnol.
PD NOV
PY 2015
VL 33
IS 11
BP 1201
EP +
DI 10.1038/nbt.3371
PG 13
WC Biotechnology & Applied Microbiology
SC Biotechnology & Applied Microbiology
GA CW3TY
UT WOS:000364916000028
PM 26501954
ER
PT J
AU Mankodi, A
Grunseich, C
Skov, M
Cook, L
Aue, G
Purev, E
Bakar, D
Lehky, T
Jurkat-Rott, K
Pedersen, TH
Childs, RW
AF Mankodi, Ami
Grunseich, Christopher
Skov, Martin
Cook, Lisa
Aue, Georg
Purev, Enkhtsetseg
Bakar, Dara
Lehky, Tanya
Jurkat-Rott, Karin
Pedersen, Thomas H.
Childs, Richard W.
TI Divalent cation-responsive myotonia and muscle paralysis in skeletal
muscle sodium channelopathy
SO NEUROMUSCULAR DISORDERS
LA English
DT Article
DE Myotonia; Paramyotonia congenita; Periodic paralysis; Muscle weakness;
Sodium channel; Magnesium
ID CALCIUM REDUCE MYOTONIA; EXTRACELLULAR MAGNESIUM;
PARAMYOTONIA-CONGENITA; PERIODIC PARALYSIS; MUTATION; GENOTYPE
AB We report a patient with paramyotonia congenita/hyperkalemic periodic paralysis due to Nav1.4 I693T mutation who had worsening of myotonia and muscle weakness in the setting of hypomagnesemia and hypocalcemia with marked recovery after magnesium administration. Computer simulations of the effects of the I693T mutation were introduced in the muscle fiber model by both hyperpolarizing shifts in the Nav1.4 channel activation and a faster recovery from slow channel inactivation. A further shift in the Nav1.4 channel activation in the hyperpolarizing direction as expected with low divalent cations resulted in myotonia that progressed to membrane inexcitability. Shifting the channel activation in the depolarizing direction as would be anticipated from magnesium supplementation abolished the myotonia. These observations provide clinical and biophysical evidence that the muscle symptoms in sodium channelopathy are sensitive to divalent cations. Exploration of the role of magnesium administration in therapy or prophylaxis is warranted with a randomized clinical trial. Published by Elsevier B.V.
C1 [Mankodi, Ami; Grunseich, Christopher; Bakar, Dara] NINDS, Neurogenet Branch, Bethesda, MD 20892 USA.
[Skov, Martin; Pedersen, Thomas H.] Univ Aarhus, Dept Biomed, DK-8000 Aarhus, Denmark.
[Cook, Lisa; Aue, Georg; Purev, Enkhtsetseg; Childs, Richard W.] NHLBI, Sect Transplantat Imnzunotherapy, Bethesda, MD 20892 USA.
[Lehky, Tanya] NINDS, Clin Neurophysiol Program, EMG Sect, Bethesda, MD 20892 USA.
[Jurkat-Rott, Karin] Univ Ulm, Div Nettrophysiol, D-89069 Ulm, Germany.
RP Mankodi, A (reprint author), NINDS, Neurogenet Branch, NIH, 35 Convent Dr,Bldg 35,Room 2A-1002, Bethesda, MD 20892 USA.
EM Ami.Mankodi@nih.gov
FU Intramural NIH HHS [Z99 NS999999]
NR 14
TC 0
Z9 0
U1 1
U2 3
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0960-8966
EI 1873-2364
J9 NEUROMUSCULAR DISORD
JI Neuromusc. Disord.
PD NOV
PY 2015
VL 25
IS 11
BP 908
EP 912
DI 10.1016/j.nmd.2015.08.007
PG 5
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA CX0BP
UT WOS:000365362200012
PM 26494408
ER
PT J
AU Grunho, M
Sonies, B
Frattali, CM
Litvan, I
AF Grunho, M.
Sonies, B.
Frattali, C. M.
Litvan, I.
TI Swallowing disturbances in the corticobasal syndrome
SO PARKINSONISM & RELATED DISORDERS
LA English
DT Article
DE Corticobasal syndrome; Swallowing; Dysphagia; Atypical parkinsonism
ID PROGRESSIVE SUPRANUCLEAR PALSY; PARKINSONS-DISEASE; DEGENERATION;
DYSPHAGIA; APRAXIA; DISORDERS; ABNORMALITIES; DYSARTHRIA; DIAGNOSIS;
FEATURES
AB Objectives: To determine the characteristics of swallowing and speech disturbances in patients with corticobasal syndrome (CBS) compared to healthy controls, and whether a subjective swallowing questionnaire, the NIH-Speech Pathology swallowing questionnaire (NIH-SQ), can predict swallowing impairment.
Methods: Twenty-four consecutive CBS patients underwent a swallowing assessment comprised of the NIH-SQ ultrasound swallow study (US) and modified barium swallow (MBS) study. Healthy controls (n = 28) completed the NIH-SQ and the US.
Results: Ninety-six percent of the patients with CBS reported at least one complaint in the NIH-SQ 59% had abnormal dry swallow duration and 10% abnormal wet swallow duration. Twenty-three patients with CBS had some abnormality on the MBS. The MBS category "piecemeal deglutition" (excessive lingual gestures causing multiple swallows required to clear a single bolus) was characteristic of CBS patients. No aspiration was detected. No NIH-SQ cutoff score or combination of subjective complaints predicted an abnormal MBS. Fifty-two percent of the patients had speech apraxia.
Conclusions: Swallowing and speech disturbances are common in patients with CBS and differ from those previously reported in patients with PSP syndrome. Piecemeal deglutition and speech apraxia are characteristic features of our CBS patients. Although the NIH-SQ cannot predict the results of the more objective MBS in this population, it characterizes the patients' major subjective swallowing complaints. Published by Elsevier Ltd.
C1 [Grunho, M.; Litvan, I.] Univ Calif San Diego, Dept Neurosci, Movement Disorders Ctr, La Jolla, CA 92037 USA.
[Sonies, B.; Frattali, C. M.] NIH, Dept Rehabil Med, Ctr Clin, Bethesda, MD 20892 USA.
RP Litvan, I (reprint author), Univ Calif San Diego, Dept Neurosci, Movement Disorders Ctr, Tasch Endowed Prof Parkinson Dis Res, 8950 Villa La Jolla Dr,Suite C112, La Jolla, CA 92037 USA.
EM ilitvan@ucsd.edu
OI Litvan, Irene/0000-0002-3485-3445
NR 30
TC 0
Z9 1
U1 1
U2 1
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1353-8020
EI 1873-5126
J9 PARKINSONISM RELAT D
JI Parkinsonism Relat. Disord.
PD NOV
PY 2015
VL 21
IS 11
BP 1342
EP 1348
DI 10.1016/j.parkreldis.2015.09.043
PG 7
WC Clinical Neurology
SC Neurosciences & Neurology
GA CW5RS
UT WOS:000365054900008
PM 26456115
ER
PT J
AU Su, XZ
Miller, LH
AF Su Xin-Zhuan
Miller, Louis H.
TI The discovery of artemisinin and the Nobel Prize in Physiology or
Medicine
SO SCIENCE CHINA-LIFE SCIENCES
LA English
DT Editorial Material
ID PLASMODIUM-FALCIPARUM MALARIA; RESISTANCE
C1 [Su Xin-Zhuan; Miller, Louis H.] NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA.
RP Su, XZ (reprint author), NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA.
EM xsu@niaid.nih.gov; lmiller@niaid.nih.gov
FU Intramural NIH HHS [Z99 AI999999]
NR 7
TC 8
Z9 9
U1 0
U2 7
PU SCIENCE PRESS
PI BEIJING
PA 16 DONGHUANGCHENGGEN NORTH ST, BEIJING 100717, PEOPLES R CHINA
SN 1674-7305
EI 1869-1889
J9 SCI CHINA LIFE SCI
JI Sci. China-Life Sci.
PD NOV
PY 2015
VL 58
IS 11
BP 1175
EP 1179
DI 10.1007/s11427-015-4948-7
PG 5
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA CW6TF
UT WOS:000365130000022
PM 26481135
ER
PT J
AU Clyne, B
Smith, SM
Hughes, CM
Boland, F
Bradley, MC
Cooper, JA
Fahey, T
AF Clyne, Barbara
Smith, Susan M.
Hughes, Carmel M.
Boland, Fiona
Bradley, Marie C.
Cooper, Janine A.
Fahey, Tom
CA OPTI-SCRIPT Study Team
TI Effectiveness of a Multifaceted Intervention for Potentially
Inappropriate Prescribing in Older Patients in Primary Care: A
Cluster-Randomized Controlled Trial (OPTI-SCRIPT Study)
SO ANNALS OF FAMILY MEDICINE
LA English
DT Article
DE randomized controlled trial; potentially inappropriate prescribing;
primary health care; prescription drugs; practice-based research
ID ELDERLY-PATIENTS; GENERAL-PRACTICE; NURSING-HOMES; PEOPLE; OUTCOMES;
RISK; BENZODIAZEPINES; QUESTIONNAIRE; POPULATION; MEDICATION
AB PURPOSE Potentially inappropriate prescribing (PIP) is common in older people and can result in increased morbidity, adverse drug events, and hospitalizations. The OPTI-SCRIPT study (Optimizing Prescribing for Older People in Primary Care, a cluster-randomized controlled trial) tested the effectiveness of a multifaceted intervention for reducing PIP in primary care.
METHODS We conducted a cluster-randomized controlled trial among 21 general practitioner practices and 196 patients with PIP. Intervention participants received a complex, multifaceted intervention incorporating academic detailing; review of medicines with web-based pharmaceutical treatment algorithms that provide recommended alternative-treatment options; and tailored patient information leaflets. Control practices delivered usual care and received simple, patient-level PIP feedback. Primary outcomes were the proportion of patients with PIP and the mean number of potentially inappropriate prescriptions. We performed intention-to-treat analysis using random-effects regression.
RESULTS All 21 practices and 190 patients were followed. At intervention completion, patients in the intervention group had significantly lower odds of having PIP than patients in the control group (adjusted odds ratio = 0.32; 95% CI, 0.15-0.70; P = .02). The mean number of PIP drugs in the intervention group was 0.70, compared with 1.18 in the control group (P = .02). The intervention group was almost one-third less likely than the control group to have PIP drugs at intervention completion, but this difference was not significant (incidence rate ratio = 0.71; 95% CI, 0.50-1.02; P = .49). The intervention was effective in reducing proton pump inhibitor prescribing (adjusted odds ratio = 0.30; 95% CI, 0.14-0.68; P = .04).
CONCLUSIONS The OPTI-SCRIPT intervention incorporating academic detailing with a pharmacist, and a review of medicines with web-based pharmaceutical treatment algorithms, was effective in reducing PIP, particularly in modifying prescribing of proton pump inhibitors, the most commonly occurring PIP drugs nationally.
C1 [Clyne, Barbara; Smith, Susan M.; Boland, Fiona; Cooper, Janine A.; Fahey, Tom] Royal Coll Surgeons Ireland, HRB Ctr Primary Care Res, Dept Gen Practice, Dublin 2, Ireland.
[Hughes, Carmel M.; Cooper, Janine A.] Queens Univ Belfast, Sch Pharm, Belfast, Antrim, North Ireland.
[Bradley, Marie C.] NCI, Rockville, MD USA.
RP Clyne, B (reprint author), Royal Coll Surgeons Ireland, HRB Ctr Primary Care Res, Dept Gen Practice, 123 St Stephens Green, Dublin 2, Ireland.
EM barbaraclyne@rcsi.ie
RI Fahey, Tom/C-9367-2012;
OI Fahey, Tom/0000-0002-5896-5783; smith, susan/0000-0001-6027-2727; Clyne,
Barbara/0000-0002-1186-9495
FU Health Research Board (HRB) PhD Scholars Programme in Health Services
Research [PHD/2007/16]; HRB Centre for Primary Care Research
[HRC/2007/1]
FX This study is independent research, funded by the Health Research Board
(HRB) PhD Scholars Programme in Health Services Research under grant
PHD/2007/16 and the HRB Centre for Primary Care Research under grant
HRC/2007/1.
NR 42
TC 11
Z9 11
U1 2
U2 11
PU ANNALS FAMILY MEDICINE
PI LEAWOOD
PA 11400 TOMAHAWK CREEK PARKWAY, LEAWOOD, KS 66211-2672 USA
SN 1544-1709
EI 1544-1717
J9 ANN FAM MED
JI Ann. Fam. Med.
PD NOV-DEC
PY 2015
VL 13
IS 6
BP 545
EP 553
DI 10.1370/afm.1838
PG 9
WC Primary Health Care; Medicine, General & Internal
SC General & Internal Medicine
GA CW2SN
UT WOS:000364843100008
PM 26553894
ER
PT J
AU Arkenau, HT
Kelly, K
Patel, MR
Neuteboom, B
Speit, I
Chin, K
Heery, CR
Gulley, JL
AF Arkenau, H. -T.
Kelly, K.
Patel, M. R.
Neuteboom, B.
Speit, I.
Chin, K.
Heery, C. R.
Gulley, J. L.
TI Phase I JAVELIN solid tumor trial of avelumab (MSB0010718C), an
anti-PD-L1 antibody: Safety and pharmacokinetics
SO ANNALS OF ONCOLOGY
LA English
DT Meeting Abstract
CT Meeting of the European-Society-for-Medical-Oncology (ESMO)
CY NOV 20-21, 2015
CL Lausanne, SWITZERLAND
SP European Soc Med Oncol, Bristol Myers Squibb, MSD, Merck, Pfizer, Roche, Celldex Therapeut
C1 [Arkenau, H. -T.] Sarah Cannon Res Inst, Drug Dev Unit, London, England.
[Kelly, K.] Univ Calif Davis, Ctr Comprehens Canc, Dept Hematol & Oncol, Sacramento, CA 95817 USA.
[Patel, M. R.] Florida Canc Specialists, Sarah Cannon Res Inst, Med Oncol, Sarasota, FL USA.
[Neuteboom, B.] EMD Serono Inc, Quantitat Pharmacol & Drug Disposit Dept, Billerica, MA USA.
[Speit, I.] Merck KGaA, Global Drug Safety, Darmstadt, Germany.
[Chin, K.] EMD Serono Inc, Inst Res & Dev, Billerica, MA USA.
[Heery, C. R.] NCI, Lab Tumor Immunol & Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Gulley, J. L.] NCI, Lab Tumor Immunol & Biol, Ctr Canc Res, Genitourinary Malignancies Branch,NIH, Bethesda, MD 20892 USA.
RI Gulley, James/K-4139-2016
OI Gulley, James/0000-0002-6569-2912
NR 0
TC 1
Z9 1
U1 2
U2 7
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 NOV
PY 2015
VL 26
SU 8
MA 8PD
BP 3
EP 3
PG 1
WC Oncology
SC Oncology
GA CW7EH
UT WOS:000365160300009
ER
PT J
AU Dueck, AC
Basch, E
Mitchell, SA
AF Dueck, Amylou C.
Basch, Ethan
Mitchell, Sandra A.
TI Development of the US NCI patient-reported outcomes version of the
common terminology criteria for adverse events
SO ANNALS OF ONCOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the Japanese-Society-of-Medical-Oncology (JSMO)
CY JUL 16-18, 2015
CL Sapporo, JAPAN
SP Japanese Soc Med Oncol
C1 [Dueck, Amylou C.] Mayo Clin, Div Hlth Sci Res, Rochester, MN USA.
[Basch, Ethan] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27515 USA.
[Mitchell, Sandra A.] Natl Canc Inst, Div Canc Control & Populat Sci, Rockville, MD USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
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 NOV
PY 2015
VL 26
SU 7
MA SY1-3
BP 26
EP 26
PG 1
WC Oncology
SC Oncology
GA CW7ED
UT WOS:000365159900066
ER
PT J
AU Pol, HH
Brouwer, R
Glahn, D
Hibar, D
Hua, X
Jahanshad, N
Abramovic, L
Franz, C
Hansell, N
Koenis, M
Mather, K
Panizzon, M
Strike, L
Swagerman, S
Wen, W
Boomsma, D
Gilmore, J
Gogtay, N
Kahn, RS
Kremen, W
Sachdev, P
Wright, M
Thompson, P
AF Pol, Hilleke Hulshoff
Brouwer, Rachel
Glahn, David
Hibar, Derrek
Hua, Xue
Jahanshad, Neda
Abramovic, Lucija
Franz, Carol
Hansell, Narelle
Koenis, Marinka
Mather, Karen
Panizzon, Matthew
Strike, Lachlan
Swagerman, Suzanne
Wen, Wei
Boomsma, Dorret
Gilmore, John
Gogtay, Nitin
Kahn, Rene S.
Kremen, William
Sachdev, Perminder
Wright, Margaret
Thompson, Paul
TI Genetic influences on longitudinal changes in subcortical volumes:
results of the ENIGMA Plasticity Working Group
SO BEHAVIOR GENETICS
LA English
DT Meeting Abstract
CT 45th Annual Meeting of the Behavior-Genetics-Association
CY JUN 20, 2015
CL San Diego, CA
SP Behav Genet Assoc
C1 [Pol, Hilleke Hulshoff; Brouwer, Rachel; Abramovic, Lucija; Koenis, Marinka] Univ Med Ctr Utrecht, Utrecht, Netherlands.
[Glahn, David] Yale Univ Med, Dept Psychiat, New Haven, CT USA.
[Hibar, Derrek; Hua, Xue; Jahanshad, Neda; Thompson, Paul] USC, Keck Sch Med, Imaging Genet Ctr, Los Angeles, CA USA.
[Franz, Carol; Panizzon, Matthew; Kremen, William] Univ Calif San Diego, La Jolla, CA 92093 USA.
[Hansell, Narelle; Wright, Margaret] Queensland Inst Med Res, Brisbane, Qld 4006, Australia.
[Mather, Karen; Wen, Wei] Univ New S Wales, Ctr Hlth Brain Ageing, Psychiat, Sydney, NSW, Australia.
[Strike, Lachlan] QIMR Berghofer Med Res Inst, Neuroimaging Genet, Brisbane, Qld, Australia.
[Swagerman, Suzanne] Vrije Univ Amsterdam, Amsterdam, Netherlands.
[Boomsma, Dorret] Vrije Univ Amsterdam, Amsterdam, Netherlands.
[Gilmore, John] Univ North Carolina Chapel Hill, Dept Psychiat, Chapel Hill, NC USA.
[Gogtay, Nitin] NIMH, NIH, Bethesda, MD USA.
[Kahn, Rene S.] Univ Med Ctr Utrecht, Rudolf Magnus Inst Neurosci, Dept Psychiat, Utrecht, Netherlands.
[Kremen, William] VA SD Ctr Excellence Stress & Mental Hlth, San Diego, CA USA.
[Sachdev, Perminder] Univ New S Wales, Sydney, NSW 2052, Australia.
RI Karen, Mather/O-9795-2016; Hansell, Narelle/A-4553-2016
OI Karen, Mather/0000-0003-4143-8941; Hansell, Narelle/0000-0002-8229-9741
NR 1
TC 0
Z9 0
U1 0
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0001-8244
EI 1573-3297
J9 BEHAV GENET
JI Behav. Genet.
PD NOV
PY 2015
VL 45
IS 6
SI SI
BP 662
EP 663
PG 2
WC Behavioral Sciences; Genetics & Heredity; Psychology, Multidisciplinary
SC Behavioral Sciences; Genetics & Heredity; Psychology
GA CW4RI
UT WOS:000364978800079
ER
PT J
AU Machiela, MJ
Chanock, SJ
AF Machiela, Mitchell J.
Chanock, Stephen J.
TI LDlink: a web-based application for exploring population-specific
haplotype structure and linking correlated alleles of possible
functional variants
SO BIOINFORMATICS
LA English
DT Article
ID ANNOTATION; GENOMES
AB A Summary: Assessing linkage disequilibrium (LD) across ancestral populations is a powerful approach for investigating population-specific genetic structure as well as functionally mapping regions of disease susceptibility. Here, we present LDlink, a web-based collection of bioinformatic modules that query single nucleotide polymorphisms (SNPs) in population groups of interest to generate haplotype tables and interactive plots. Modules are designed with an emphasis on ease of use, query flexibility, and interactive visualization of results. Phase 3 haplotype data from the 1000 Genomes Project are referenced for calculating pairwise metrics of LD, searching for proxies in high LD, and enumerating all observed haplotypes. LDlink is tailored for investigators interested in mapping common and uncommon disease susceptibility loci by focusing on output linking correlated alleles and highlighting putative functional variants.
C1 [Machiela, Mitchell J.; Chanock, Stephen J.] NCI, Div Canc Epidemiol & Genet, Rockville, MD 20892 USA.
RP Machiela, MJ (reprint author), NCI, Div Canc Epidemiol & Genet, Rockville, MD 20892 USA.
OI Machiela, Mitchell/0000-0001-6538-9705
FU National Cancer Institute's Intramural Research Program; Division of
Cancer Epidemiology and Genetics Informatics Tool Challenge
FX Support comes from the National Cancer Institute's Intramural Research
Program and the Division of Cancer Epidemiology and Genetics Informatics
Tool Challenge.
NR 7
TC 25
Z9 25
U1 1
U2 4
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1367-4803
EI 1460-2059
J9 BIOINFORMATICS
JI Bioinformatics
PD NOV 1
PY 2015
VL 31
IS 21
BP 3555
EP 3557
DI 10.1093/bioinformatics/btv402
PG 3
WC Biochemical Research Methods; Biotechnology & Applied Microbiology;
Computer Science, Interdisciplinary Applications; Mathematical &
Computational Biology; Statistics & Probability
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Computer Science; Mathematical & Computational Biology; Mathematics
GA CW6UT
UT WOS:000365134400024
PM 26139635
ER
PT J
AU Kerridge, BT
Saha, TD
Chou, SP
Zhang, HT
Jung, JS
Ruan, WJ
Smith, SM
Huang, BJ
Hasin, DS
AF Kerridge, Bradley T.
Saha, Tulshi D.
Chou, S. Patricia
Zhang, Haitao
Jung, Jeesun
Ruan, W. June
Smith, Sharon M.
Huang, Boji
Hasin, Deborah S.
TI Gender and nonmedical prescription opioid use and DSM-5 nonmedical
prescription opioid use disorder: Results from the National
Epidemiologic Survey on Alcohol and Related Conditions - III
SO DRUG AND ALCOHOL DEPENDENCE
LA English
DT Article
DE Opioid use disorder; Gender differences; Comorbidity; Disability;
Treatment
ID SUBSTANCE USE DISORDERS; GENERAL-POPULATION SAMPLE; CHRONIC NONCANCER
PAIN; DRUG-USE DISORDERS; CHRONIC BACK-PAIN; UNITED-STATES;
OLDER-ADULTS; PSYCHIATRIC-DISORDERS; PROCEDURAL VALIDITY; CLINICAL-TRIAL
AB Background: Little is known about sex-specific risk for nonmedical prescription opioid use (NMPOU) and DSM-5 nonmedical prescription opioid use disorder (NMPOUD). The objective of the present study was to present prevalence, correlates, psychiatric comorbidity, treatment and disability of NMPOU and DSM-5 NMPOUD among men and women.
Methods: Nationally representative sample of the U.S.
Results: Prevalences of 12-month and lifetime NMPOU were greater among men (4.4%, 13.0%) than women (3.9%, 9.8%), while corresponding rates of DSM-5 NMPOUD did not differ between men (0.9%, 2.2%) and women (0.9%, 1.9%). Regardless of time frame and sex, NMPOU and NMPOUD generally decreased with age and were lower among Blacks, Asians/Pacific Islanders and Hispanics, and respondents with lower socioeconomic status. Among men with NMPOU, rates were lower among respondents in the Northeast and South and among those previously married (lifetime). Across time frames and gender, NMPOU and NMPOUD were generally associated with other substance use disorders, posttraumatic stress and borderline, schizotypal and antisocial personality disorders, but associated with major depressive disorder, persistent depression and bipolar I disorder only among men. Disability increased with NMPOU frequency and NMPOUD severity. Only 7.6% and 8.2% of men and women with NMPOU ever received treatment, while 26.8% and 31.1% ever received treatment for NMPOUD.
Conclusions: NMPOU and NMPOUD are highly disabling, associated with a broad array of sex-specific and shared correlates and comorbidities and largely go untreated in the U.S. Valid assessment tools are needed that include gender as a stratification variable to identify NMPOU and NMPOUD. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
C1 [Kerridge, Bradley T.] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY 10032 USA.
[Saha, Tulshi D.; Chou, S. Patricia; Zhang, Haitao; Jung, Jeesun; Ruan, W. June; Smith, Sharon M.; Huang, Boji] NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH, Bethesda, MD 20892 USA.
[Hasin, Deborah S.] Columbia Univ, Dept Psychiat, Coll Phys & Surg, New York, NY 10032 USA.
[Hasin, Deborah S.] Columbia Univ, Mailman Sch Publ, Hlth, New York, NY 10032 USA.
[Hasin, Deborah S.] New York State Psychiat Inst & Hosp, New York, NY 10032 USA.
RP Kerridge, BT (reprint author), Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY 10032 USA.
EM BradleyKerridge@gmail.com
FU National Institute on Alcohol Abuse and Alcoholism
FX The NESARC-III was funded and sponsored by the National Institute on
Alcohol Abuse and Alcoholism, with supplemented support from the
National Institute on Drug Abuse. The sponsors had no involvement in the
study design, collection, analysis and interpretation of the data, in
the writing of the report and in the decision to submit the article for
publication.
NR 85
TC 4
Z9 4
U1 3
U2 6
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0376-8716
EI 1879-0046
J9 DRUG ALCOHOL DEPEN
JI Drug Alcohol Depend.
PD NOV 1
PY 2015
VL 156
BP 47
EP 56
DI 10.1016/j.drugalcdep.2015.08.026
PG 10
WC Substance Abuse; Psychiatry
SC Substance Abuse; Psychiatry
GA CW5SN
UT WOS:000365057000006
PM 26374990
ER
PT J
AU Wu, LT
Ghitza, UE
Batch, BC
Pencina, MJ
Rojas, LF
Goldstein, BA
Schibler, T
Dunham, AA
Rusincovitch, S
Brady, KT
AF Wu, Li-Tzy
Ghitza, Udi E.
Batch, Bryan C.
Pencina, Michael J.
Rojas, Leoncio Flavio
Goldstein, Benjamin A.
Schibler, Tony
Dunham, Ashley A.
Rusincovitch, Shelley
Brady, Kathleen T.
TI Substance use and mental diagnoses among adults with and without type 2
diabetes: Results from electronic health records data
SO DRUG AND ALCOHOL DEPENDENCE
LA English
DT Article
DE Anxiety disorder; Comorbidity; Diabetes mellitus; Electronic health
records; Mood disorder; Substance use disorder
ID PRIMARY-CARE; COLLABORATIVE CARE; GENERAL-PRACTICE; MEDICAL-RECORDS; USE
DISORDERS; DEPRESSION; METAANALYSIS; ANXIETY; ALCOHOL; ABUSE
AB Background: Comorbid diabetes and substance use diagnoses (SUD) represent a hazardous combination, both in terms of healthcare cost and morbidity. To date, there is limited information about the association of SUD and related mental disorders with type 2 diabetes mellitus (T2DM).
Methods: We examined the associations between T2DM and multiple psychiatric diagnosis categories, with a focus on SUD and related psychiatric comorbidities among adults with T2DM. We analyzed electronic health record (EHR) data on 170,853 unique adults aged >= 18 years from the EHR warehouse of a large academic healthcare system. Logistic regression analyses were conducted to estimate the strength of an association for comorbidities.
Results: Overall, 9% of adults (n = 16,243) had T2DM. Blacks, Hispanics, Asians, and Native Americans had greater odds of having T2DM than whites. All 10 psychiatric diagnosis categories were more prevalent among adults with T2DM than among those without T2DM. Prevalent diagnoses among adults with T2MD were mood (21.22%), SUD (17.02%: tobacco 13.25%, alcohol 4.00%, drugs 4.22%), and anxiety diagnoses (13.98%). Among adults with T2DM, SUD was positively associated with mood, anxiety, personality, somatic, and schizophrenia diagnoses.
Conclusions: We examined a large diverse sample of individuals and found clinical evidence of SUD and psychiatric comorbidities among adults with T2DM. These results highlight the need to identify feasible collaborative care models for adults with T2DM and SUD related psychiatric comorbidities, particularly in primary care settings, that will improve behavioral health and reduce health risk. (C) 2015 The Authors. Published by Elsevier Ireland Ltd.
C1 [Wu, Li-Tzy] Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC 27710 USA.
[Wu, Li-Tzy; Pencina, Michael J.; Rojas, Leoncio Flavio; Goldstein, Benjamin A.; Schibler, Tony] Duke Univ, Duke Clin Res Inst, Durham, NC 27710 USA.
[Ghitza, Udi E.] NIDA, Bethesda, MD 20892 USA.
[Batch, Bryan C.] Duke Univ, Med Ctr, Div Endocrinol, Durham, NC 27710 USA.
[Pencina, Michael J.; Goldstein, Benjamin A.] Duke Univ, Dept Biostat & Bioinformat, Durham, NC 27710 USA.
[Dunham, Ashley A.; Rusincovitch, Shelley] Duke Univ, Duke Translat Res Inst, Durham, NC 27710 USA.
[Brady, Kathleen T.] Med Univ S Carolina, South Carolina Clin & Translat Res Inst, Charleston, SC 29425 USA.
RP Wu, LT (reprint author), Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Sch Med, Box 3903, Durham, NC 27710 USA.
EM litzy.wu@duke.edu
FU U.S. National Institutes of Health [U10DA013727, R01MD007658,
UG1DA040317]; Centers for Medicare and Medicaid Services [1C1CMS331018];
Bristol-Myers Squibb Foundation
FX This work was made possible by research support from the U.S. National
Institutes of Health (U10DA013727; R01MD007658; UG1DA040317), the
Centers for Medicare and Medicaid Services (1C1CMS331018), and the
Bristol-Myers Squibb Foundation. The sponsoring agency had no further
role in the study design and analysis, the writing of the report, or the
decision to submit the paper for publication. The opinions expressed in
this paper are solely those of the authors and do not represent the
official position of the U.S. government and the Bristol-Myers Squibb
Foundation.
NR 62
TC 4
Z9 4
U1 0
U2 7
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0376-8716
EI 1879-0046
J9 DRUG ALCOHOL DEPEN
JI Drug Alcohol Depend.
PD NOV 1
PY 2015
VL 156
BP 162
EP 169
DI 10.1016/j.drugalcdep.2015.09.003
PG 8
WC Substance Abuse; Psychiatry
SC Substance Abuse; Psychiatry
GA CW5SN
UT WOS:000365057000022
PM 26392231
ER
PT J
AU Pilkonis, PA
Yu, L
Dodds, NE
Johnston, KL
Lawrence, SM
Hilton, TF
Daley, DC
Patkar, AA
McCarty, D
AF Pilkonis, Paul A.
Yu, Lan
Dodds, Nathan E.
Johnston, Kelly L.
Lawrence, Suzanne M.
Hilton, Thomas F.
Daley, Dennis C.
Patkar, Ashwin A.
McCarty, Dennis
TI Item banks for substance use from the Patient-Reported Outcomes
Measurement Information System (PROMIS (R)): Severity of use and
positive appeal of use
SO DRUG AND ALCOHOL DEPENDENCE
LA English
DT Article
DE Substance use; Drug use; Item response theory; Measurement
ID NATIONAL EPIDEMIOLOGIC SURVEY; RESPONSE THEORY ANALYSIS;
CLINICAL-TRIALS-NETWORK; SCREENING-TEST ASSIST; DRUG-ABUSE-TREATMENT;
USE DISORDERS; DSM-IV; ALCOHOL-USE; TREATMENT PROGRAMS; SHORT FORMS
AB Background: Two item banks for substance use were developed as part of the Patient-Reported Outcomes Measurement Information System (PROMIS (R)): severity of substance use and positive appeal of substance use.
Methods: Qualitative item analysis (including focus groups, cognitive interviewing, expert review, and item revision) reduced an initial pool of more than 5300 items for substance use to 119 items included in field testing. Items were written in a first-person, past-tense format, with 5 response options reflecting frequency or severity. Both 30-day and 3-month time frames were tested. The calibration sample of 1336 respondents included 875 individuals from the general population (ascertained through an internet panel) and 461 patients from addiction treatment centers participating in the National Drug Abuse Treatment Clinical Trials Network.
Results: Final banks of 37 and 18 items were calibrated for severity of substance use and positive appeal of substance use, respectively, using the two-parameter graded response model from item response theory (IRT). Initial calibrations were similar for the 30-day and 3-month time frames, and final calibrations used data combined across the time frames, making the items applicable with either interval. Seven-item static short forms were also developed from each item bank.
Conclusions: Test information curves showed that the PROMIS item banks provided substantial information in a broad range of severity, making them suitable for treatment, observational, and epidemiological research in both clinical and community settings. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
C1 [Pilkonis, Paul A.; Yu, Lan; Dodds, Nathan E.; Johnston, Kelly L.; Lawrence, Suzanne M.; Daley, Dennis C.] Univ Pittsburgh, Sch Med, Dept Psychiat, Pittsburgh, PA 15213 USA.
[Yu, Lan] Univ Pittsburgh, Sch Med, Dept Med, Pittsburgh, PA 15213 USA.
[Hilton, Thomas F.] NIDA, Indian Harbor Beach, FL 32937 USA.
[Patkar, Ashwin A.] Duke Univ, Sch Med, Dept Psychiat, Durham, NC 27705 USA.
[Patkar, Ashwin A.] Duke Univ, Sch Med, Dept Community & Family Med, Durham, NC 27705 USA.
[McCarty, Dennis] Oregon Hlth & Sci Univ, Publ Hlth & Prevent Med, Portland, OR 97239 USA.
RP Pilkonis, PA (reprint author), Western Psychiat Inst & Clin, 3811 OHara St, Pittsburgh, PA 15213 USA.
EM pilkonispa@upmc.edu
FU National Institutes of Health (NIH) Common Fund Initiative (Northwestern
University) [U54AR057951, U01AR052177]; Northwestern University
[U54AR057943]; American Institutes for Research [U54AR057926]; State
University of New York, Stony Brook [U01AR057948, U01AR052170];
University of Washington, Seattle [U01AR057954, U01AR052171]; University
of North Carolina, Chapel Hill [U01AR052181]; Children's Hospital of
Philadelphia [U01AR057956]; Stanford University [U01AR052158]; Boston
University [U01AR057929]; University of California, Los Angeles; MSHS
[U01AR057936]; University of Pittsburgh [U01AR052155]; Georgetown
University [U01AR057971]; Children's Hospital Medical Center, Cincinnati
[U01AR057940]; University of Maryland, Baltimore [U01AR057967]; Duke
University [U01AR052186]; National Institute on Drug Abuse [UG1
DA015815]
FX PROMIS (R) was funded with cooperative agreements from the National
Institutes of Health (NIH) Common Fund Initiative (Northwestern
University, PI: David Cella, PhD, U54AR057951, U01AR052177; Northwestern
University, PI: Richard C. Gershon, PhD, U54AR057943; American
Institutes for Research, PI: Susan (San) D. Keller, PhD, U54AR057926;
State University of New York, Stony Brook, PIs: Joan E. Broderick, PhD
and Arthur A. Stone, PhD, U01AR057948, U01AR052170; University of
Washington, Seattle, PIs: Heidi M. Crane, MD, MPH, Paul K. Crane, MD,
MPH, and Donald L. Patrick, PhD, U01AR057954; University of Washington,
Seattle, PI: Dagmar Amtmann, PhD, U01AR052171; University of North
Carolina, Chapel Hill, PI: Harry A. Guess, MD, PhD (deceased), Darren A.
DeWalt, MD, MPH, U01AR052181; Children's Hospital of Philadelphia, PI:
Christopher B. Forrest, MD, PhD, U01AR057956; Stanford University, PI:
James F. Fries, MD, U01AR052158; Boston University, PIs: Alan Jette, PT,
PhD, Stephen M. Haley, PhD (deceased), and David Scott Tulsky, PhD
(University of Michigan, Ann Arbor), U01AR057929; University of
California, Los Angeles, PIs: Dinesh Khanna, MD (University of Michigan,
Ann Arbor) and Brennan Spiegel, MD, MSHS, U01AR057936; University of
Pittsburgh, PI: Paul A. Pilkonis, PhD, U01AR052155; Georgetown
University, PIs: Carol. M. Moinpour, PhD (Fred Hutchinson Cancer
Research Center, Seattle) and Arnold L. Potosky, PhD, U01AR057971;
Children's Hospital Medical Center, Cincinnati, PI: Esi M. Morgan
DeWitt, MD, MSCE, U01AR057940; University of Maryland, Baltimore, PI:
Lisa M. Shulman, MD, U01AR057967; and Duke University, PI: Kevin P.
Weinfurt, PhD, U01AR052186). NIH Science Officers on this project have
included Deborah Ader, PhD, Vanessa Ameen, MD (deceased), Susan
Czajkowski, PhD, Basil Eldadah, MD, PhD, Lawrence Fine, MD, DrPH,
Lawrence Fox, MD, PhD, Lynne Haverkos, MD, MPH, Thomas Hilton, PhD,
Laura Lee Johnson, PhD, Michael Kozak, PhD, Peter Lyster, PhD, Donald
Mattison, MD, Claudia Moy, PhD, Louis Quatrano, PhD, Bryce Reeve, PhD,
William Riley, PhD, Peter Scheidt, MD, Ashley Wilder Smith, PhD, MPH,
Susana Serrate-Sztein, MD, William Phillip Tonkins, DrPH, Ellen Werner,
PhD, Tisha Wiley, PhD, and James Witter, MD, PhD. An award from the
National Institute on Drug Abuse (UG1 DA015815) provided additional
support for Dennis McCarty's participation. This article uses data
developed under PROMIS. These contents do not necessarily represent an
endorsement by the US Government or PROMIS. See www.nihpromis.org for
additional information on the PROMIS (R) initiative.
NR 48
TC 2
Z9 2
U1 4
U2 5
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0376-8716
EI 1879-0046
J9 DRUG ALCOHOL DEPEN
JI Drug Alcohol Depend.
PD NOV 1
PY 2015
VL 156
BP 184
EP 192
DI 10.1016/j.drugalcdep.2015.09.008
PG 9
WC Substance Abuse; Psychiatry
SC Substance Abuse; Psychiatry
GA CW5SN
UT WOS:000365057000025
PM 26423364
ER
PT J
AU Kleiner, DE
Bedossa, P
AF Kleiner, David E.
Bedossa, Pierre
TI Liver Histology and Clinical Trials for Nonalcoholic
Steatohepatitis-Perspectives From 2 Pathologists
SO GASTROENTEROLOGY
LA English
DT Editorial Material
ID FATTY LIVER; FOLLOW-UP; SCORING SYSTEM; DISEASE; PROGRESSION; FIBROSIS;
BIOPSIES; NAFLD; PIOGLITAZONE; MULTICENTER
C1 [Kleiner, David E.] NCI, Bethesda, MD 20892 USA.
[Bedossa, Pierre] Univ Paris Diderot, UFR Med, Paris, France.
RP Kleiner, DE (reprint author), NCI, Bethesda, MD 20892 USA.
FU Intramural NIH HHS
NR 26
TC 7
Z9 7
U1 0
U2 4
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0016-5085
EI 1528-0012
J9 GASTROENTEROLOGY
JI Gastroenterology
PD NOV
PY 2015
VL 149
IS 6
BP 1305
EP 1308
DI 10.1053/j.gastro.2015.09.015
PG 4
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA CW6GN
UT WOS:000365095800010
PM 26409177
ER
PT J
AU Schoen, RE
Razzak, A
Yu, KJ
Berndt, SI
Firl, K
Riley, TL
Pinsky, PF
AF Schoen, Robert E.
Razzak, Anthony
Yu, Kelly J.
Berndt, Sonja I.
Firl, Kevin
Riley, Thomas L.
Pinsky, Paul F.
TI Incidence and Mortality of Colorectal Cancer in Individuals With a
Family History of Colorectal Cancer
SO GASTROENTEROLOGY
LA English
DT Article
DE Adenomatous Polyps; Colon Cancer; Genetic Risk Factors; Screening
ID AMERICAN-COLLEGE; SURVEILLANCE COLONOSCOPY; RISK; GASTROENTEROLOGY;
METAANALYSIS; PREVENTION; ENDOSCOPY; GUIDELINE; DATABASE; SOCIETY
AB BACKGROUND & AIMS: Little is known about the change in risk conferred by family history of colorectal cancer (CRC) as a person ages. We evaluated the effect of family history on CRC incidence and mortality after 55 years of age, when the risk of early onset cancer had passed. METHODS: We collected data from participants in the randomized, controlled Prostate, Lung, Colorectal and Ovarian cancer screening trial of flexible sigmoidoscopy versus usual care (55-74 years old, no history of CRC), performed at 10 US centers from 1993 to 2001. A detailed family history of colorectal cancer was obtained at enrollment, and subjects were followed for CRC incidence and mortality for up to 13 years. RESULTS: Among 144,768 participants, 14,961 subjects (10.3%) reported a family of CRC. Of 2090 incident cases, 273 cases (13.1%) had a family history of CRC; among 538 deaths from CRC, 71 (13.2%) had a family history of CRC. Overall, family history of CRC was associated with an increased risk of CRC incidence (hazard ratio [HR], 1.30; 95% confidence interval [CI], 1.10-1.50; P<.0001) and increased mortality (HR, 1.31; 95% CI, 1.02-1.69; P=.03). Subjects with 1 first degree relative (FDR) with CRC (n = 238; HR, 1.23; 95% CI, 1.07-1.42) or >= 2 FDRs with CRC (n = 35; HR, 2.04; 95% CI, 1.44-2.86) were at increased risk for incident CRC. However, among individuals with 1 FDR with CRC, there were no differences in risk based on age at diagnosis in the FDR (for FDR <60 years of age: HR, 1.27; 95% CI, 0.97-1.63; for FDR 60-70 years of age: HR, 1.33; 95% CI, 1.06-1.62; for FDR >70 years of age: HR, 1.14; 95% CI, 0.93-1.45; P trend = .59). CONCLUSIONS: After 55 years of age, subjects with 1 FDR with CRC had only a modest increase in risk for CRC incidence and death; age of onset in the FDR was not significantly associated with risk. Individuals with >= 2 FDRs with CRC had continued increased risk in older age. Guidelines and clinical practice for subjects with a family history of CRC should be modified to align CRC testing to risk.
C1 [Schoen, Robert E.; Razzak, Anthony] Univ Pittsburgh, Div Gastroenterol Hepatol & Nutr, Pittsburgh, PA USA.
[Yu, Kelly J.; Pinsky, Paul F.] NCI, Canc Prevent Div, Bethesda, MD 20892 USA.
[Berndt, Sonja I.; Firl, Kevin] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Riley, Thomas L.] Informat Management Serv Inc, Rockville, MD USA.
RP Schoen, RE (reprint author), Div Gastroenterol Hepatol & Nutr, Mezzanine Level,C Wing,PUH 200 Lothrop St, Pittsburgh, PA 15213 USA.
EM rschoen@pitt.edu
OI Firl, Kevin/0000-0002-7598-0299
FU Division of Cancer Prevention, National Cancer Institute [N01-CN-25511]
FX This work was supported by the Division of Cancer Prevention, National
Cancer Institute contract N01-CN-25511 to the University of Pittsburgh
Cancer Institute.
NR 27
TC 8
Z9 8
U1 0
U2 1
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0016-5085
EI 1528-0012
J9 GASTROENTEROLOGY
JI Gastroenterology
PD NOV
PY 2015
VL 149
IS 6
BP 1438
EP +
DI 10.1053/j.gastro.2015.07.055
PG 9
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA CW6GN
UT WOS:000365095800032
PM 26255045
ER
PT J
AU Huang, CR
Haritunians, T
Okou, DT
Cutler, DJ
Zwick, ME
Taylor, KD
Datta, LW
Maranville, JC
Liu, ZQ
Ellis, S
Chopra, P
Alexander, JS
Baldassano, RN
Cross, RK
Dassopoulos, T
Dhere, TA
Duerr, RH
Hanson, JS
Hou, JK
Hussain, SZ
Isaacs, KL
Kachelries, KE
Kader, H
Kappelman, MD
Katz, J
Kellermayer, R
Kirschner, BS
Kuemmerle, JF
Kumar, A
Kwon, JH
Lazarev, M
Mannon, P
Moulton, DE
Osuntokun, BO
Patel, A
Rioux, JD
Rotter, JI
Saeed, S
Scherl, EJ
Silverberg, MS
Silverman, A
Targan, SR
Valentine, JF
Wang, MH
Simpson, CL
Bridges, SL
Kimberly, RP
Rich, SS
Cho, JH
Di Rienzo, A
Kao, LWH
McGovern, DPB
Brant, SR
Kugathasan, S
AF Huang, Chengrui
Haritunians, Talin
Okou, David T.
Cutler, David J.
Zwick, Michael E.
Taylor, Kent D.
Datta, Lisa W.
Maranville, Joseph C.
Liu, Zhenqiu
Ellis, Shannon
Chopra, Pankaj
Alexander, Jonathan S.
Baldassano, Robert N.
Cross, Raymond K.
Dassopoulos, Themistocles
Dhere, Tanvi A.
Duerr, Richard H.
Hanson, John S.
Hou, Jason K.
Hussain, Sunny Z.
Isaacs, Kim L.
Kachelries, Kelly E.
Kader, Howard
Kappelman, Michael D.
Katz, Jeffrey
Kellermayer, Richard
Kirschner, Barbara S.
Kuemmerle, John F.
Kumar, Archana
Kwon, John H.
Lazarev, Mark
Mannon, Peter
Moulton, Dedrick E.
Osuntokun, Bankole O.
Patel, Ashish
Rioux, John D.
Rotter, Jerome I.
Saeed, Shehzad
Scherl, Ellen J.
Silverberg, Mark S.
Silverman, Ann
Targan, Stephan R.
Valentine, John F.
Wang, Ming-Hsi
Simpson, Claire L.
Bridges, S. Louis
Kimberly, Robert P.
Rich, Stephen S.
Cho, Judy H.
Di Rienzo, Anna
Kao, Linda W. H.
McGovern, Dermot P. B.
Brant, Steven R.
Kugathasan, Subra
TI Characterization of Genetic Loci That Affect Susceptibility to
Inflammatory Bowel Diseases in African Americans
SO GASTROENTEROLOGY
LA English
DT Article
DE Race; Ethnicity; Genetic Variant; Intestinal Inflammation
ID GENOME-WIDE ASSOCIATION; CROHNS-DISEASE; JAPANESE POPULATION;
ULCERATIVE-COLITIS; RISK; CAUCASIANS; ADMIXTURE; PREVALENCE; PREDICTORS;
ANCESTRY
AB BACKGROUND & AIMS: Inflammatory bowel disease (IBD) has familial aggregation in African Americans (AAs), but little is known about the molecular genetic susceptibility. Mapping studies using the Immunochip genotyping array expand the number of susceptibility loci for IBD in Caucasians to 163, but the contribution of the 163 loci and European admixture to IBD risk in AAs is unclear. We performed a genetic mapping study using the Immunochip to determine whether IBD susceptibility loci in Caucasians also affect risk in AAs and identify new associated loci. METHODS: We recruited AAs with IBD and without IBD (controls) from 34 IBD centers in the United States; additional controls were collected from 4 other Immunochip studies. Association and admixture loci were mapped for 1088 patients with Crohn's disease, 361 with ulcerative colitis, 62 with IBD type unknown, and 1797 controls; 130,241 autosomal single-nucleotide polymorphisms (SNPs) were analyzed. RESULTS: The strongest associations were observed between ulcerative colitis and HLA rs9271366 (P = 7.5 x 10(-6)), Crohn's disease and 5p13.1 rs4286721 (P = 3.5 x 10(-6)), and IBD and KAT2A rs730086 (P = 2.3 x 10(-6)). Additional suggestive associations (P < 4.2 x 10(-5)) were observed between Crohn's disease and IBD and African-specific SNPs in STAT5A and STAT3; between IBD and SNPs in IL23R, IL12B, and C2orf43; and between ulcerative colitis and SNPs near HDAC11 and near LINC00994. The latter 3 loci have not been previously associated with IBD, but require replication. Established Caucasian associations were replicated in AAs (P < 3.1 x 10(-4)) at NOD2, IL23R, 5p15.3, and IKZF3. Significant admixture (P < 3.9 x 10(-4)) was observed for 17q12-17q21.31 (IZKF3 through STAT3), 10q11.23-10q21.2, 15q22.2-15q23, and 16p12.2-16p12.1. Network analyses showed significant enrichment (false discovery rate < 1 x 10(-5)) in genes that encode members of the JAK-STAT, cytokine, and chemokine signaling pathways, as well those involved in pathogenesis of measles. CONCLUSIONS: In a genetic analysis of 3308 AA IBD cases and controls, we found that many variants associated with IBD in Caucasians also showed association evidence with these diseases in AAs; we also found evidence for variants and loci not previously associated with IBD. The complex genetic factors that determine risk for or protection against IBD in different populations require further study.
C1 [Huang, Chengrui; Kao, Linda W. H.; Brant, Steven R.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21231 USA.
[Haritunians, Talin; Liu, Zhenqiu; McGovern, Dermot P. B.] Cedars Sinai Med Ctr, F Widjaja Fdn Inflammatory Bowel & Immunobiol Res, Los Angeles, CA 90048 USA.
[Okou, David T.; Kumar, Archana; Kugathasan, Subra] Emory Univ, Sch Med, Dept Pediat, Atlanta, GA USA.
[Taylor, Kent D.; Rotter, Jerome I.] Harbor UCLA Med Ctr, Inst Translat Genom & Populat Sci, Torrance, CA 90509 USA.
[Taylor, Kent D.; Rotter, Jerome I.] Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Dept Pediat, Div Genom Outcomes, Torrance, CA 90509 USA.
[Taylor, Kent D.; Rotter, Jerome I.] Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Dept Med, Torrance, CA 90509 USA.
[Cutler, David J.; Zwick, Michael E.; Chopra, Pankaj] Emory Univ, Sch Med, Dept Human Genet, Atlanta, GA USA.
[Datta, Lisa W.; Ellis, Shannon; Lazarev, Mark; Wang, Ming-Hsi; Brant, Steven R.] Johns Hopkins Univ, Sch Med, Meyerhoff Inflammatory Bowel Dis Ctr, Dept Med, Baltimore, MD 21231 USA.
[Maranville, Joseph C.; Di Rienzo, Anna] Univ Chicago, Comm Clin Pharmacol & Pharmacogen, Chicago, IL 60637 USA.
[Maranville, Joseph C.; Di Rienzo, Anna] Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA.
[Alexander, Jonathan S.] Louisiana State Univ, Hlth Sci Ctr, Dept Mol & Cellular Physiol, Shreveport, LA 71105 USA.
[Baldassano, Robert N.; Kachelries, Kelly E.] Childrens Hosp Philadelphia, Div Gastroenterol & Nutr, Philadelphia, PA 19104 USA.
[Cross, Raymond K.] Univ Maryland, Div Gastroenterol, Baltimore, MD 21201 USA.
[Dassopoulos, Themistocles] Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA.
[Dhere, Tanvi A.] Emory Univ, Sch Med, Dept Med, Atlanta, GA USA.
[Duerr, Richard H.] Univ Pittsburgh, Sch Med, Dept Med, Div Gastroenterol Hepatol & Nutr, Pittsburgh, PA 15213 USA.
[Duerr, Richard H.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Human Genet, Pittsburgh, PA 15261 USA.
[Hanson, John S.] PLLC, Charlotte Gastroenterol & Hepatol, Charlotte, NC USA.
[Hou, Jason K.] Baylor Coll Med, Dept Med, Houston, TX 77030 USA.
[Hou, Jason K.] Michael E DeBakey VA Med Ctr, VA HSR&D Ctr Innovat Qual Effectiveness & Safety, Houston, TX USA.
[Hussain, Sunny Z.] Willis Knighton Phys Network, Dept Pediat, Shreveport, LA USA.
[Isaacs, Kim L.] Univ N Carolina, Div Gastroenterol & Hepatol, Chapel Hill, NC USA.
[Kader, Howard] Univ Maryland, Sch Med, Dept Pediat, Baltimore, MD 21201 USA.
[Kappelman, Michael D.] Univ N Carolina, Dept Pediat, Chapel Hill, NC USA.
[Katz, Jeffrey] Case Western Reserve Univ, Div Gastroenterol, Cleveland, OH 44106 USA.
[Kellermayer, Richard] Baylor Coll Med, Sect Pediat Gastroenterol, Houston, TX 77030 USA.
[Kirschner, Barbara S.] Univ Chicago, Comer Childrens Hosp, Dept Pediat, Chicago, IL 60637 USA.
[Kuemmerle, John F.] Virginia Commonwealth Univ, Dept Med, Med Coll Virginia Campus, Richmond, VA 23298 USA.
[Kuemmerle, John F.] Virginia Commonwealth Univ, Med Coll Virginia Campus, Dept Physiol & Biophys, VCU Program Enter Neuromuscular Sci, Richmond, VA 23298 USA.
[Kwon, John H.] Univ Chicago, Dept Med, Gastroenterol Sect, Chicago, IL 60637 USA.
[Mannon, Peter] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA.
[Moulton, Dedrick E.] Vanderbilt Childrens Hosp, Div Gastroenterol, Nashville, TN USA.
[Osuntokun, Bankole O.] Cook Childrens Med Ctr, Dept Pediat, Ft Worth, TX USA.
[Patel, Ashish] Univ Texas SW Med Ctr Dallas, Dept Pediat, Dallas, TX 75390 USA.
[Rioux, John D.] Univ Montreal, Montreal, PQ, Canada.
[Rioux, John D.] Montreal Heart Inst, Res Ctr, Montreal, PQ H1T 1C8, Canada.
[Saeed, Shehzad] Cincinnati Childrens Hosp Med Ctr, Div Gastroenterol Hepatol & Nutr, Cincinnati, OH 45229 USA.
[Scherl, Ellen J.] Weill Cornell Med Coll, Dept Med, New York, NY USA.
[Silverberg, Mark S.] Univ Toronto, Samuel Lunenfeld Res Inst, Dept Med, Dept Surg,Dept Publ Hlth Sci,Dept Immunol, Toronto, ON, Canada.
[Silverberg, Mark S.] Univ Toronto, Samuel Lunenfeld Res Inst, Dept Mol & Med Genet, Toronto, ON, Canada.
[Silverberg, Mark S.] Toronto Gen Hosp, Mt Sinai Hosp, Res Inst, Toronto, ON, Canada.
[Silverman, Ann] Henry Ford Hlth Syst, Dept Gastroenterol, Detroit, MI USA.
[Valentine, John F.] Univ Utah, Div Gastroenterol Hepatol & Nutr, Salt Lake City, UT USA.
[Simpson, Claire L.] NHGRI, Stat Genet Sect, Inherited Dis Res Branch, NIH, Baltimore, MD USA.
[Bridges, S. Louis; Kimberly, Robert P.] Univ Alabama Birmingham, Div Clin Immunol & Rheumatol, Birmingham, AL 35294 USA.
[Rich, Stephen S.] Univ Virginia, Sch Med, Ctr Publ Hlth Genom, Charlottesville, VA 22908 USA.
[Cho, Judy H.] Icahn Sch Med Mt Sinai, Dept Med, New York, NY 10029 USA.
RP Brant, SR (reprint author), Johns Hopkins Univ, Sch Med, Meyerhoff Inflammatory Bowel Dis Ctr, 1501 E Jefferson St,B136, Baltimore, MD 21231 USA.
EM sbrant@jhmi.edu
RI Rioux, John/A-9599-2015; Silverberg, Mark/B-4183-2008;
OI Rioux, John/0000-0001-7560-8326; Ellis, Shannon/0000-0002-9231-0481;
Kimberly, Robert/0000-0002-5330-3086
FU National Institutes of Health (NIH) [DK062431, DK087694, DK062413,
DK046763-19, AI067068, U54DE023789-01, DK062429, DK062422, DK062420,
DK062432, DK062423]; Harvey M. and Lynn P. Meyerhoff Inflammatory Bowel
Disease Center; Morton Hyatt Family; Buford and Linda Lewis family;
Marcus foundation; Joshua L and Lisa Z Greer Endowed Chair; Agency for
Healthcare Research and Quality [HS021747]; European Union [305479];
Leona M. and Harry B. Helmsley Charitable Trust; Veterans Administration
HSR&D Center for Innovations in Quality, Effectiveness and Safety [CIN
13-413]; Michael E. DeBakey VA Medical Center; NIH/National Heart, Lung,
and Blood Institute [HL06957]; Consortium for the Longitudinal
Evaluation of African-Americans with Early Rheumatoid Arthritis (CLEAR);
NIH [N01-AR-02247, AR-62278, P01-AR49084, M01-RR-00032]; University of
Alabama General Clinical Research Center [M01-RR-00032]; PROFILE Study
group coordinated at the University of Alabama Birmingham; Type 1
Diabetes Genetics Consortium [U01 DK062418]; National Institute of
Diabetes and Digestive and Kidney Diseases; National Institute of
Allergy and Infectious Diseases; National Center for Human Genome
Research; Eunice Kennedy Shriver National Institute of Child Health and
Human Development; Juvenile Diabetes Research Foundation; Intramural
Research Program of the National Human Genome Research Institute,
National Institutes of Health
FX This work supported by National Institutes of Health (NIH) grants
DK062431 (S.R.B.), DK087694 (S.K.), DK062413 (D.P.B.M and K.T),
DK046763-19, AI067068, and U54DE023789-01 (D.P.B.M.), DK062429 and
DK062422 (J.H.C.), DK062420 (R.H.D.), DK062432 (J.D.R.), and DK062423
(M.S.S.). Additional support from Harvey M. and Lynn P. Meyerhoff
Inflammatory Bowel Disease Center, the Morton Hyatt Family, the Buford
and Linda Lewis family (S.R.B.); endowed professorship from Marcus
foundation (S.K.); The Joshua L and Lisa Z Greer Endowed Chair, HS021747
from the Agency for Healthcare Research and Quality, grant 305479 from
the European Union, and The Leona M. and Harry B. Helmsley Charitable
Trust (D.P.B.M.); from the Veterans Administration HSR&D Center for
Innovations in Quality, Effectiveness and Safety (#CIN 13-413) and the
Michael E. DeBakey VA Medical Center (J.K.H.). PARC control samples
supported by NIH/National Heart, Lung, and Blood Institute grant HL06957
(Ronald M. Krauss, principal investigator). Rheumatoid arthritis control
samples recruited and supported by the Consortium for the Longitudinal
Evaluation of African-Americans with Early Rheumatoid Arthritis (CLEAR),
NIH grants N01-AR-02247 and AR-62278 (S.L.B.) and the University of
Alabama General Clinical Research Center (M01-RR-00032); systemic lupus
erythematosus control samples recruited and supported by the PROFILE
Study group coordinated at the University of Alabama Birmingham and
supported by NIH grants P01-AR49084 (R.P.K.) and M01-RR-00032; type 1
diabetes control samples recruited and supported by the Type 1 Diabetes
Genetics Consortium U01 DK062418 (S.S.R.), and sponsored by the National
Institute of Diabetes and Digestive and Kidney Diseases, National
Institute of Allergy and Infectious Diseases, National Center for Human
Genome Research, Eunice Kennedy Shriver National Institute of Child
Health and Human Development, and the Juvenile Diabetes Research
Foundation. C.L.S. is supported by the Intramural Research Program of
the National Human Genome Research Institute, National Institutes of
Health.
NR 37
TC 13
Z9 13
U1 2
U2 9
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0016-5085
EI 1528-0012
J9 GASTROENTEROLOGY
JI Gastroenterology
PD NOV
PY 2015
VL 149
IS 6
BP 1575
EP 1586
DI 10.1053/j.gastro.2015.07.065
PG 12
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA CW6GN
UT WOS:000365095800046
PM 26278503
ER
PT J
AU Park, JE
Vanegas-Arroyave, N
Hallett, M
Lungu, C
AF Park, Jung E.
Vanegas-Arroyave, Nora
Hallett, Mark
Lungu, Codrin
TI A Woman With a Novel Mutation of THAP1 With a Prominent Response to Deep
Brain Stimulation of the Globus Pallidus Internus
SO JAMA NEUROLOGY
LA English
DT Editorial Material
ID DYSTONIA
C1 [Park, Jung E.; Vanegas-Arroyave, Nora; Hallett, Mark] NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA.
[Vanegas-Arroyave, Nora; Lungu, Codrin] NINDS, Off Clin Director, NIH, Bethesda, MD 20892 USA.
RP Park, JE (reprint author), NINDS, Human Motor Control Sect, NIH, 10 Ctr Dr,Bldg 10,Room 7D42, Bethesda, MD 20892 USA.
EM junge.park@nih.gov
FU Intramural NIH HHS
NR 4
TC 0
Z9 0
U1 1
U2 2
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 2168-6149
EI 2168-6157
J9 JAMA NEUROL
JI JAMA Neurol.
PD NOV
PY 2015
VL 72
IS 11
BP 1369
EP 1369
DI 10.1001/jamaneurol.2015.1954
PG 1
WC Clinical Neurology
SC Neurosciences & Neurology
GA CW1ZO
UT WOS:000364790900023
PM 26415042
ER
PT J
AU Freeman, WD
Brazis, PW
Biller, J
Masdeu, JC
Merrilees, GR
Olson, S
AF Freeman, William David
Brazis, Paul W.
Biller, Jose
Masdeu, Joseph C.
Merrilees, G. Robert
Olson, Sandra
TI In Memoriam: Frank A. Rubino, MD
SO JAMA NEUROLOGY
LA English
DT Biographical-Item
C1 [Freeman, William David; Brazis, Paul W.] Mayo Clin, Dept Neurol, Jacksonville, FL 32224 USA.
[Biller, Jose] Loyola Univ Chicago, Stritch Sch Med, Dept Neurol, Maywood, IL USA.
[Masdeu, Joseph C.] NIMH, Clin Brain Disorders Branch, Sect Integrat Neuroimaging, Intramural Res Program,Dept Neurol,NIH, Bethesda, MD 20892 USA.
[Merrilees, G. Robert] US Coast Guard, Natl Aeronaut & Space Adm, Merritt Isl, FL USA.
[Olson, Sandra] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA.
RP Freeman, WD (reprint author), Mayo Clin, Dept Neurol, 4500 San Pablo Rd, Jacksonville, FL 32224 USA.
EM freeman.william1@mayo.edu
NR 2
TC 0
Z9 0
U1 0
U2 0
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 2168-6149
EI 2168-6157
J9 JAMA NEUROL
JI JAMA Neurol.
PD NOV
PY 2015
VL 72
IS 11
BP 1384
EP 1385
PG 2
WC Clinical Neurology
SC Neurosciences & Neurology
GA CW1ZO
UT WOS:000364790900032
PM 26551966
ER
PT J
AU Takeuchi, M
Kastner, DL
Remmers, EF
AF Takeuchi, Masaki
Kastner, Daniel L.
Remmers, Elaine F.
TI The immunogenetics of Behcet's disease: A comprehensive review
SO JOURNAL OF AUTOIMMUNITY
LA English
DT Review
DE Behcet's disease; GWAS; HLA-B*51; ERAP1; Disease-associated genetic
variants
ID GENOME-WIDE ASSOCIATION; INFLAMMATORY-BOWEL-DISEASE; FAMILIAL
MEDITERRANEAN FEVER; HLA CLASS-I; PSORIASIS SUSCEPTIBILITY LOCI; MHC
CLASS-I; ANKYLOSING-SPONDYLITIS; GENETIC ASSOCIATION; JAPANESE PATIENTS;
CHINESE HAN
AB Behcet's disease is a chronic multisystem inflammatory disorder characterized mainly by recurrent oral ulcers, ocular involvement, genital ulcers, and skin lesions, presenting with remissions and exacerbations. It is thought that both environmental and genetic factors contribute to its onset and development. Although the etiology of Behget's disease remains unclear, recent immunogenetic findings are providing clues to its pathogenesis. In addition to the positive association of HLA-B*51, which was identified more than four decades ago, and which has since been confirmed in multiple populations, recent studies report additional independent associations in the major histocompatibility complex class I region. HLA-B*15, -B*27, -B*57, and -A*26 are independent risk factors for Behget's disease, while HLA-B*49 and -A*03 are independent class I alleles that are protective for Behcet's disease. Genome-wide association studies have identified associations with genome-wide significance (P < 5 x 10(-8)) in the IL23R-1L12RB2, STAT4, CCR1-CCR3, KLRC4, ERAP1, TNFAIP3, and FUT2 loci. In addition, targeted next-generation sequencing has revealed the involvement of rare nonsynonymous variants of IL23R, TLR4, NOD2, and MEW in Behcet's disease pathogenesis. Significant differences in gene function or mRNA expression associated with the risk alleles of the disease susceptibility loci suggest which genes in a disease-associated locus influence disease pathogenesis. These genes encompass both innate and adaptive immunity and confirm the importance of the predominant polarization towards helper T cell (Th) 1 versus Th2 cells, and the involvement of Th17 cells. In addition, epistasis observed between HLA-B*51 and the risk coding haplotype of the endoplasmic reticulum-associated protease, ERAPI, provides a clue that an HLA class I-peptide presentation-based mechanism contributes to this complex disease. Published by Elsevier Ltd.
C1 [Takeuchi, Masaki; Kastner, Daniel L.; Remmers, Elaine F.] NHGRI, Inflammatory Dis Sect, Metab Cardiovasc & Inflammatory Dis Genom Branch, NIH, Bethesda, MD 20892 USA.
[Takeuchi, Masaki] Yokohama City Univ, Grad Sch Med, Ophthalmol & Visual Sci, Kanazawa Ku, Yokohama, Kanagawa 2360004, Japan.
RP Remmers, EF (reprint author), NHGRI, Inflammatory Dis Sect, Metab Cardiovasc & Inflammatory Dis Genom Branch, NIH, Bethesda, MD 20892 USA.
EM elaine.remmers@nih.gov
FU Intramural NIH HHS [Z99 HG999999, Z01 AR041083-19]
NR 134
TC 18
Z9 19
U1 2
U2 11
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0896-8411
EI 1095-9157
J9 J AUTOIMMUN
JI J. Autoimmun.
PD NOV
PY 2015
VL 64
SI SI
BP 137
EP 148
DI 10.1016/j.jaut.2015.08.013
PG 12
WC Immunology
SC Immunology
GA CW3LT
UT WOS:000364894500013
PM 26347074
ER
PT J
AU Glaser, R
Dimitrakakis, C
AF Glaser, R.
Dimitrakakis, C.
TI Testosterone and breast cancer prevention
SO MATURITAS
LA English
DT Review
DE Testosterone; Breast cancer; Prevention; Aromatase; Anastrozole; Therapy
ID AROMATASE EXPRESSION; ANDROGEN RECEPTOR; HORMONE-THERAPY; WOMEN; TISSUE;
INFLAMMATION; ANASTROZOLE; INHIBITOR
AB Testosterone (T) is the most abundant biologically active hormone in women. Androgen receptors (AR) are located throughout the body including the breast where T decreases tissue proliferation. However, T can be aromatized to estradiol (E2), which increases proliferation and hence, breast cancer (BCA) risk. Increased aromatase expression and an imbalance in the ratio of stimulatory estrogens to protective androgens impacts breast homeostasis.
Recent clinical data supports a role for T in BCA prevention. Women with symptoms of hormone deficiency treated with pharmacological doses of T alone or in combination with anastrozole (A), delivered by subcutaneous implants, had a reduced incidence of BCA. In addition, T combined with A effectively treated symptoms of hormone deficiency in BCA survivors and was not associated with recurrent disease. Most notably, T+A implants placed in breast tissue surrounding malignant tumors significantly reduced BCA tumor size, further supporting T direct antiproliferative, protective and therapeutic effect. (C) 2015 The Authors. Published by Elsevier Ireland Ltd. All rights reserved.
C1 [Glaser, R.] Millennium Wellness Ctr, Dayton, OH 45458 USA.
[Glaser, R.] Wright State Univ, Boonshoft Sch Med, Dept Surg, Dayton, OH 45435 USA.
[Dimitrakakis, C.] Univ Athens, Sch Med, Dept Ob Gyn 1, Athens 11528, Greece.
[Dimitrakakis, C.] NICHD, NIH, Bethesda, MD 20892 USA.
RP Glaser, R (reprint author), Millennium Wellness Ctr, 228 E Spring Valley Rd, Dayton, OH 45458 USA.
EM rglaser@woh.rr.com; rglasermd@gmail.com
NR 30
TC 4
Z9 4
U1 1
U2 3
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0378-5122
EI 1873-4111
J9 MATURITAS
JI Maturitas
PD NOV
PY 2015
VL 82
IS 3
BP 291
EP 295
DI 10.1016/j.maturitas.2015.06.002
PG 5
WC Geriatrics & Gerontology; Obstetrics & Gynecology
SC Geriatrics & Gerontology; Obstetrics & Gynecology
GA CW3HQ
UT WOS:000364883000009
PM 26160683
ER
PT J
AU Blanchard, H
Chang, LS
Rezvani, AH
Rapoport, SI
Taha, AY
AF Blanchard, Helene
Chang, Lisa
Rezvani, Amir H.
Rapoport, Stanley I.
Taha, Ameer Y.
TI Brain Arachidonic Acid Incorporation and Turnover are not Altered in the
Flinders Sensitive Line Rat Model of Human Depression
SO NEUROCHEMICAL RESEARCH
LA English
DT Article
DE Depression model; Arachidonic acid; Turnover; Metabolism; Flinders
Sensitive Line rat; Fatty acids; Brain lipid concentrations; Kinetic
ID POSITRON-EMISSION-TOMOGRAPHY; CHRONIC ANTIDEPRESSANT TREATMENT;
THIN-LAYER CHROMATOGRAPHY; GENETIC ANIMAL-MODEL; PHOSPHOLIPASE A(2);
UNANESTHETIZED RATS; SEROTONIN TRANSPORTER; RECEPTOR-BINDING; REUPTAKE
TRANSPORTER; SIGNAL-TRANSDUCTION
AB Brain serotonergic signaling is coupled to arachidonic acid (AA)-releasing calcium-dependent phospholipase A(2). Increased brain serotonin concentrations and disturbed serotonergic neurotransmission have been reported in the Flinders Sensitive Line (FSL) rat model of depression, suggesting that brain AA metabolism may be elevated. To test this hypothesis, C-14-AA was intravenously infused to steady-state levels into control and FSL rats derived from the same Sprague-Dawley background strain, and labeled and unlabeled brain phospholipid and plasma fatty acid concentrations were measured to determine the rate of brain AA incorporation and turnover. Brain AA incorporation and turnover did not differ significantly between controls and FSL rats. Compared to controls, plasma unesterified docosahexaenoic acid was increased, and brain phosphatidylinositol AA and total lipid linoleic acid and n-3 and n-6 docosapentaenoic acid were significantly decreased in FSL rats. Several plasma esterified fatty acids differed significantly from controls. In summary, brain AA metabolism did not change in FSL rats despite reported increased levels of serotonin concentrations, suggesting possible post-synaptic dampening of serotonergic neurotransmission involving AA.
C1 [Blanchard, Helene; Chang, Lisa; Rapoport, Stanley I.] NIA, Brain Physiol & Metab Sect, Neurosci Lab, NIH, Bethesda, MD 20892 USA.
[Rezvani, Amir H.] Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC USA.
[Taha, Ameer Y.] Univ Calif Davis, Coll Agr & Environm Sci, Dept Food Sci & Technol, Davis, CA 95616 USA.
RP Taha, AY (reprint author), Univ Calif Davis, Coll Agr & Environm Sci, Dept Food Sci & Technol, RMI North,Room 3162, Davis, CA 95616 USA.
EM ataha@ucdavis.edu
FU National Institute on Aging
FX Research was supported by the Intramural Research Program of the
National Institute on Aging.
NR 50
TC 0
Z9 0
U1 2
U2 5
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0364-3190
EI 1573-6903
J9 NEUROCHEM RES
JI Neurochem. Res.
PD NOV
PY 2015
VL 40
IS 11
BP 2293
EP 2303
DI 10.1007/s11064-015-1719-6
PG 11
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA CW6CQ
UT WOS:000365085500014
PM 26404538
ER
PT J
AU Song, SB
Garrido, L
Nagy, Z
Mohammadi, S
Steel, A
Driver, J
Dolan, RJ
Duchaine, B
Furl, N
AF Song, Sunbin
Garrido, Lucia
Nagy, Zoltan
Mohammadi, Siawoosh
Steel, Adam
Driver, Jon
Dolan, Ray J.
Duchaine, Bradley
Furl, Nicholas
TI Local but not long-range microstructural differences of the ventral
temporal cortex in developmental prosopagnosia
SO NEUROPSYCHOLOGIA
LA English
DT Article
DE Diffusion-weighted imaging; Inferior longitudinal fasciculus; Inferior
fronto-occipital fasciculus; Prosopagnosia; Face perception; Individual
differences
ID DIFFUSION TENSOR TRACTOGRAPHY; FACE PROCESSING NETWORK; CONGENITAL
PROSOPAGNOSIA; DETAILED EXPLORATION; ALZHEIMERS-DISEASE; WEIGHTED MRI;
SPIN-ECHO; CONNECTIVITY; RECOGNITION; SUBJECT
AB Individuals with developmental prosopagnosia (DP) experience face recognition impairments despite normal intellect and low-level vision and no history of brain damage. Prior studies using diffusion tensor imaging in small samples of subjects with DP (n=6 or n=8) offer conflicting views on the neurobiological bases for DP, with one suggesting white matter differences in two major long-range tracts running through the temporal cortex, and another suggesting white matter differences confined to fibers local to ventral temporal face-specific functional regions of interest (fROIs) in the fusiform gyrus. Here, we address these inconsistent findings using a comprehensive set of analyzes in a sample of DP subjects larger than both prior studies combined (n=16). While we found no microstructural differences in long-range tracts between DP and age-matched control participants, we found differences local to face-specific fROIs, and relationships between these microstructural measures with face recognition ability. We conclude that subtle differences in local rather than long-range tracts in the ventral temporal lobe are more likely associated with developmental prosopagnosia. (C) 2015 The Authors. Published by Elsevier Ltd.
C1 [Song, Sunbin; Steel, Adam] NIH, Human Cort Physiol Sect, Natl Inst Neurol Disorders & Stroke, Bethesda, MD 20892 USA.
[Garrido, Lucia] Brunel Univ, Div Psychol, Dept Life Sci, Uxbridge UB8 3PH, Middx, England.
[Nagy, Zoltan] Univ Zurich, Lab Social & Neural Syst Res SNS Lab, CH-8091 Zurich, Switzerland.
[Nagy, Zoltan; Mohammadi, Siawoosh; Driver, Jon; Dolan, Ray J.] UCL, Wellcome Trust Ctr Neuroimaging, London WC1N 3BG, England.
[Mohammadi, Siawoosh] Univ Med Ctr Hamburg Eppendorf, Dept Syst Neurosci, Hamburg, Germany.
[Driver, Jon] UCL, Inst Cognit Neurosci, London WC1N 3AR, England.
[Duchaine, Bradley] Dartmouth Coll, Psychol & Brain Sci, Hanover, NH 03755 USA.
[Furl, Nicholas] Univ London, Royal Holloway & Bedford New Coll, Dept Psychol, Egham TW20 0EX, Surrey, England.
RP Song, SB (reprint author), NIH, Human Cort Physiol Sect, Natl Inst Neurol Disorders & Stroke, Bethesda, MD 20892 USA.
EM songss@mail.nih.gov
RI Mohammadi, Siawoosh/H-9539-2012;
OI Mohammadi, Siawoosh/0000-0003-1311-9636; furl,
nicholas/0000-0003-2488-1343; Steel, Adam/0000-0001-8876-933X; Nagy,
Zoltan/0000-0001-6611-6362
FU ESRC [RES-061-23-0040]; Deutsche Forschungsgemeinschaft (DFG) [MO
2397/1-1]; Fundacao para a Ciencia e a Tecnologia (FCT)
[SFRH/BD/22580/2005]; Wellcome Trust [079866/Z/06/Z]
FX We are grateful to our DP participants for their involvement in the
study. Funding was provided by ESRC (RES-061-23-0040) to B. D., by the
Deutsche Forschungsgemeinschaft (DFG, MO 2397/1-1) to S.M., and by the
Fundacao para a Ciencia e a Tecnologia (FCT) (SFRH/BD/22580/2005) to
L.G. The Wellcome Trust (079866/Z/06/Z) to Z.N., N.F., S.M. covered
scanning costs.
NR 60
TC 10
Z9 10
U1 0
U2 3
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 NOV
PY 2015
VL 78
BP 195
EP 206
DI 10.1016/j.neuropsychologia.2015.10.010
PG 12
WC Behavioral Sciences; Neurosciences; Psychology, Experimental
SC Behavioral Sciences; Neurosciences & Neurology; Psychology
GA CW5RH
UT WOS:000365053800020
PM 26456436
ER
PT J
AU Svetkey, LP
Batch, BC
Lin, PH
Intille, SS
Corsino, L
Tyson, CC
Bosworth, HB
Grambow, SC
Voils, C
Loria, C
Gallis, JA
Schwager, J
Bennett, GB
AF Svetkey, Laura P.
Batch, Bryan C.
Lin, Pao-Hwa
Intille, Stephen S.
Corsino, Leonor
Tyson, Crystal C.
Bosworth, Hayden B.
Grambow, Steven C.
Voils, Corrine
Loria, Catherine
Gallis, John A.
Schwager, Jenifer
Bennett, Gary B.
TI Cell phone intervention for you (CITY): A randomized, controlled trial
of behavioral weight loss intervention for young adults using mobile
technology
SO OBESITY
LA English
DT Article
ID BODY-MASS INDEX; CLINICAL-TRIALS; PHYSICAL-ACTIVITY; BLOOD-PRESSURE;
RISK; DIET; OVERWEIGHT; PREVENTION; STRATEGIES; SUCCESS
AB ObjectiveTo determine the effect on weight of two mobile technology-based (mHealth) behavioral weight loss interventions in young adults.
MethodsRandomized, controlled comparative effectiveness trial in 18- to 35-year-olds with BMI25 kg/m(2) (overweight/obese), with participants randomized to 24 months of mHealth intervention delivered by interactive smartphone application on a cell phone (CP); personal coaching enhanced by smartphone self-monitoring (PC); or Control.
ResultsThe 365 randomized participants had mean baseline BMI of 35 kg/m(2). Final weight was measured in 86% of participants. CP was not superior to Control at any measurement point. PC participants lost significantly more weight than Controls at 6 months (net effect -1.92 kg [CI -3.17, -0.67], P=0.003), but not at 12 and 24 months.
ConclusionsDespite high intervention engagement and study retention, the inclusion of behavioral principles and tools in both interventions, and weight loss in all treatment groups, CP did not lead to weight loss, and PC did not lead to sustained weight loss relative to Control. Although mHealth solutions offer broad dissemination and scalability, the CITY results sound a cautionary note concerning intervention delivery by mobile applications. Effective intervention may require the efficiency of mobile technology, the social support and human interaction of personal coaching, and an adaptive approach to intervention design.
C1 [Svetkey, Laura P.; Lin, Pao-Hwa; Tyson, Crystal C.; Schwager, Jenifer] Duke Univ, Med Ctr, Dept Med, Div Nephrol, Durham, NC 27710 USA.
[Svetkey, Laura P.; Lin, Pao-Hwa; Schwager, Jenifer] Duke Mol Physiol Inst, Sarah W Stedman Nutr & Metab Ctr, Durham, NC USA.
[Batch, Bryan C.; Corsino, Leonor] Duke Univ, Med Ctr, Dept Med, Div Endocrinol Metab & Nutr, Durham, NC 27710 USA.
[Intille, Stephen S.] Northeastern Univ, Coll Comp & Informat Sci, Boston, MA 02115 USA.
[Intille, Stephen S.] Northeastern Univ, Bouve Coll Hlth Sci, Boston, MA 02115 USA.
[Bosworth, Hayden B.; Voils, Corrine] Duke Univ, Med Ctr, Dept Med, Div Gen Internal Med, Durham, NC 27710 USA.
[Bosworth, Hayden B.] Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC 27710 USA.
[Bosworth, Hayden B.] Duke Univ, Med Ctr, Sch Nursing, Durham, NC 27710 USA.
[Bosworth, Hayden B.] Durham Vet Affairs Med Ctr, Ctr Hlth Serv Res Primary Care, Durham, NC USA.
[Grambow, Steven C.] Duke Univ, Med Ctr, Dept Biostat & Bioinformat, Durham, NC 27710 USA.
[Gallis, John A.] NHLBI, Div Cardiovasc Sci, NIH, Bethesda, MD 20892 USA.
[Bennett, Gary B.] Duke Univ, Dept Psychol & Neurosci, Durham, NC 27710 USA.
[Bennett, Gary B.] Duke Univ, Med Ctr, Duke Obes Prevent Program, Durham, NC 27710 USA.
RP Svetkey, LP (reprint author), Duke Univ, Med Ctr, Dept Med, Div Nephrol, Durham, NC 27710 USA.
EM svetk001@mc.duke.edu
RI Emchi, Karma/Q-1952-2016
FU National Heart, Lung, and Blood Institute, a component of the National
Institutes of Health (NIH) [U01HL096720]
FX The CITY study was sponsored by grant number U01HL096720 from the
National Heart, Lung, and Blood Institute, a component of the National
Institutes of Health (NIH).
NR 37
TC 9
Z9 9
U1 5
U2 26
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1930-7381
EI 1930-739X
J9 OBESITY
JI Obesity
PD NOV
PY 2015
VL 23
IS 11
BP 2133
EP 2141
DI 10.1002/oby.21226
PG 9
WC Endocrinology & Metabolism; Nutrition & Dietetics
SC Endocrinology & Metabolism; Nutrition & Dietetics
GA CV9SG
UT WOS:000364626300001
PM 26530929
ER
PT J
AU Gluck, ME
Alonso-Alonso, M
Piaggi, P
Weise, CM
Jumpertz-von Schwartzenberg, R
Reinhardt, M
Wassermann, EM
Venti, CA
Votruba, SB
Krakoff, J
AF Gluck, Marci E.
Alonso-Alonso, Miguel
Piaggi, Paolo
Weise, Christopher M.
Jumpertz-von Schwartzenberg, Reiner
Reinhardt, Martin
Wassermann, Eric M.
Venti, Colleen A.
Votruba, Susanne B.
Krakoff, Jonathan
TI Neuromodulation targeted to the prefrontal cortex induces changes in
energy intake and weight loss in obesity
SO OBESITY
LA English
DT Article
ID DIRECT-CURRENT STIMULATION; BRAIN POLARIZATION; FOOD-CONSUMPTION; LESS
ACTIVATION; SELF-CONTROL; LEAN WOMEN; HUMANS; MEAL; SATIATION; SYSTEM
AB ObjectiveObesity is associated with decreased activity in the prefrontal cortex. Transcranial direct current stimulation (tDCS) modifies cortical excitability and may facilitate improved control of eating. The energy intake (EI) and body weight in subjects who received cathodal versus sham (study 1) and subsequent anodal versus sham (study 2) tDCS aimed at the left dorsolateral prefrontal cortex (LDLPFC) were measured.
MethodsNine (3m, 6f) healthy volunteers with obesity (9415 kg [MSD]; 42 +/- 8 y) were admitted as inpatients for 9 days to participate in a double-blind, randomized, placebo-controlled crossover experiment. Study 1: following 5 days of a weight-maintaining diet, participants received cathodal or sham tDCS (2mA, 40min) on three consecutive mornings and then ate ad libitum from a computerized vending machine, which recorded EI. Weight was measured daily. Study 2: participants repeated the study, maintaining original assignment to active (this time anodal) and sham.
ResultsParticipants tended to consume fewer kilocalories per day (P=0.07), significantly fewer kilocalories from soda (P=0.02) and fat (P=0.03), and had a greater % weight loss (P=0.009) during anodal versus cathodal tDCS.
ConclusionsThe results indicated a role for the LDLPFC in obesity and food intake. This proof of concept study suggested, for the first time, the potential application of anodal tDCS to facilitate weight loss.
C1 [Gluck, Marci E.; Piaggi, Paolo; Weise, Christopher M.; Jumpertz-von Schwartzenberg, Reiner; Reinhardt, Martin; Venti, Colleen A.; Votruba, Susanne B.; Krakoff, Jonathan] NIDDK, Phoenix Epidemiol & Clin Res Branch, NIH, Phoenix, AZ USA.
[Alonso-Alonso, Miguel] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Lab Bariatr & Nutr Neurosci,Ctr Study Nutr Med, Boston, MA USA.
[Weise, Christopher M.] Univ Leipzig, Dept Neurol, D-04109 Leipzig, Germany.
[Wassermann, Eric M.] NINDS, Behav Neurol Unit, NIH, Bethesda, MD 20892 USA.
RP Gluck, ME (reprint author), NIDDK, Phoenix Epidemiol & Clin Res Branch, NIH, Phoenix, AZ USA.
EM gmarci@mail.nih.gov
FU National Institutes of Health (NIH); National Institute of Diabetes and
Digestive and Kidney Diseases (NIDDK); Boston Nutrition and Obesity
Research Center [P30 DK046200]; Nutrition Obesity Research Center at
Harvard [P30 DK040561]; Center for Nutritional Research Charitable Trust
FX This research was funded by the Intramural Research Program of the
National Institutes of Health (NIH) and the National Institute of
Diabetes and Digestive and Kidney Diseases (NIDDK). Dr. Alonso-Alonso is
a recipient of grants from the Boston Nutrition and Obesity Research
Center, P30 DK046200, the Nutrition Obesity Research Center at Harvard,
P30 DK040561, and the Center for Nutritional Research Charitable Trust.
The funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
NR 37
TC 9
Z9 9
U1 2
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1930-7381
EI 1930-739X
J9 OBESITY
JI Obesity
PD NOV
PY 2015
VL 23
IS 11
BP 2149
EP 2156
DI 10.1002/oby.21313
PG 8
WC Endocrinology & Metabolism; Nutrition & Dietetics
SC Endocrinology & Metabolism; Nutrition & Dietetics
GA CV9SG
UT WOS:000364626300003
PM 26530931
ER
PT J
AU Solomon, SB
Cortes-Puch, I
Sun, JF
Remy, KE
Wang, D
Feng, J
Khan, SS
Sinchar, D
Kim-Shapiro, DB
Klein, HG
Natanson, C
AF Solomon, Steven B.
Cortes-Puch, Irene
Sun, Junfeng
Remy, Kenneth E.
Wang, Dong
Feng, Jing
Khan, Sameena S.
Sinchar, Derek
Kim-Shapiro, Daniel B.
Klein, Harvey G.
Natanson, Charles
TI Transfused older stored red blood cells improve the clinical course and
outcome in a canine lethal hemorrhage and reperfusion model
SO TRANSFUSION
LA English
DT Article
ID INHALED NITRIC-OXIDE; STORAGE DURATION; CARDIAC-SURGERY; FREE
HEMOGLOBIN; SHOCK; IRON; RESUSCITATION; TRIAL; INFLAMMATION; INJURY
AB BACKGROUNDIn canine models, transfused older stored red blood cells (RBCs) hemolyze in vivo resulting in significantly increased intravascular cell-free hemoglobin (CFH) and non-transferrin-bound iron (NTBI). During canine bacterial pneumonia with septic shock, but not in controls, older stored RBCs were associated with significantly increased lung injury and mortality. It is unknown if in shock without infection transfusion of older RBCs will result in similar adverse effects.
STUDY DESIGN AND METHODSTwo-year-old purpose-bred beagles (n=12) were transfused similar quantities of either older (42-day) or fresher (7-day) stored universal donor canine RBCs 2.5 hours after undergoing controlled hemorrhage (55 mL/kg).
RESULTSWith older transfused RBCs, CFH (p<0.0001) and NTBI (p=0.004) levels increased, but lung injury (p=0.01) and C-reactive protein levels (p=0.002) declined and there was a trend toward lower mortality (18% vs. 50%). All three deaths after transfused fresher RBCs resulted from hepatic fractures. Lowered exogenous norepinephrine requirements (p<0.05) and cardiac outputs (p<0.05) after older transfused RBCs were associated with increased CFH levels that have known vasoconstrictive nitric oxide scavenging capability.
CONCLUSIONSIn hemorrhagic shock, older RBCs altered resuscitation physiology but did not worsen clinical outcomes. Elevated CFH may lower norepinephrine requirements and cardiac outputs ameliorating reperfusion injuries. With hemorrhagic shock, NTBI levels persist in contrast to the increased clearance, lung injury, and mortality in the previously reported infection model. These preclinical data suggest that whereas iron derived from older RBCs promotes bacterial growth, worsening septic shock mortality during infection, release of CFH and NTBI during hemorrhagic shock is not necessarily harmful.
C1 [Solomon, Steven B.; Cortes-Puch, Irene; Sun, Junfeng; Remy, Kenneth E.; Wang, Dong; Feng, Jing; Khan, Sameena S.; Natanson, Charles] NIH, Ctr Clin, Dept Crit Care Med, Bethesda, MD 20892 USA.
[Khan, Sameena S.] Univ Coll Dublin, Dublin 2, Ireland.
[Sinchar, Derek] Univ Pittsburgh, Vasc Med Inst, Pittsburgh, PA USA.
[Kim-Shapiro, Daniel B.] Wake Forest Univ, Dept Phys, Winston Salem, NC 27109 USA.
[Kim-Shapiro, Daniel B.] Wake Forest Univ, Translat Sci Ctr, Winston Salem, NC 27109 USA.
[Klein, Harvey G.] NIH, Ctr Clin, Dept Transfus Med, Bethesda, MD 20892 USA.
RP Solomon, SB (reprint author), NIH, Ctr Clin, Dept Crit Care Med, 10 Ctr Dr,Room 2C145, Bethesda, MD 20892 USA.
EM SSolomon@cc.nih.gov
FU US government; NIH [HL058091, HL098032]
FX The work by the authors was done as part of US government-funded
research; however, the opinions expressed are not necessarily those of
the National Institutes of Health.; Supported by intramural NIH funds.
NIH external grants HL058091 and HL098032 were used to support this
study.
NR 44
TC 3
Z9 3
U1 0
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0041-1132
EI 1537-2995
J9 TRANSFUSION
JI Transfusion
PD NOV
PY 2015
VL 55
IS 11
BP 2552
EP 2563
DI 10.1111/trf.13213
PG 12
WC Hematology
SC Hematology
GA CW3EZ
UT WOS:000364876100006
PM 26175134
ER
PT J
AU Cortes-Puch, I
Remy, KE
Solomon, SB
Sun, JF
Wang, D
Al-Hamad, M
Kelly, SM
Sinchar, D
Bellavia, L
Kanias, T
Popovsky, MA
Kim-Shapiro, DB
Klein, HG
Natanson, C
AF Cortes-Puch, Irene
Remy, Kenneth E.
Solomon, Steven B.
Sun, Junfeng
Wang, Dong
Al-Hamad, Mariam
Kelly, Seth M.
Sinchar, Derek
Bellavia, Landon
Kanias, Tamir
Popovsky, Mark A.
Kim-Shapiro, Daniel B.
Klein, Harvey G.
Natanson, Charles
TI In a canine pneumonia model of exchange transfusion, altering the age
but not the volume of older red blood cells markedly alters outcome
SO TRANSFUSION
LA English
DT Article
ID IN-HOSPITAL MORTALITY; STORED-BLOOD; STAPHYLOCOCCUS-AUREUS; STORAGE
DURATION; CARDIAC-SURGERY; FREE HEMOGLOBIN; NITRIC-OXIDE; IRON;
ASSOCIATION; FRESH
AB BACKGROUNDMassive exchange transfusion of 42-day-old red blood cells (RBCs) in a canine model of Staphylococcus aureus pneumonia resulted in in vivo hemolysis with increases in cell-free hemoglobin (CFH), transferrin-bound iron (TBI), non-transferrin-bound iron (NTBI), and mortality. We have previously shown that washing 42-day-old RBCs before transfusion significantly decreased NTBI levels and mortality, but washing 7-day-old RBCs increased mortality and CFH levels. We now report the results of altering volume, washing, and age of RBCs.
STUDY DESIGN AND METHODSTwo-year-old purpose-bred infected beagles were transfused with increasing volumes (5-10, 20-40, or 60-80 mL/kg) of either 42- or 7-day-old RBCs (n=36) or 80 mL/kg of either unwashed or washed RBCs with increasing storage age (14, 21, 28, or 35 days; n=40).
RESULTSAll volumes transfused (5-80 mL/kg) of 42-day-old RBCs resulted in alike (i.e., not significantly different) increases in TBI during transfusion as well as in CFH, lung injury, and mortality rates after transfusion. Transfusion of 80 mL/kg RBCs stored for 14, 21, 28, and 35 days resulted in increased CFH and NTBI in between levels found at 7 and 42 days of storage. However, washing RBCs of intermediate ages (14-35 days) does not alter NTBI and CFH levels or mortality rates.
CONCLUSIONSPreclinical data suggest that any volume of 42-day-old blood potentially increases risks during established infection. In contrast, even massive volumes of 7-day-old blood result in minimal CFH and NTBI levels and risks. In contrast to the extremes of storage, washing blood stored for intermediate ages does not alter risks of transfusion or NTBI and CFH clearance.
C1 [Cortes-Puch, Irene; Remy, Kenneth E.; Solomon, Steven B.; Sun, Junfeng; Wang, Dong; Al-Hamad, Mariam; Kelly, Seth M.; Natanson, Charles] NIH, Ctr Clin, Dept Crit Care Med, Bethesda, MD 20892 USA.
[Klein, Harvey G.] NIH, Ctr Clin, Dept Transfus Med, Bethesda, MD 20892 USA.
[Sinchar, Derek; Kanias, Tamir] Univ Pittsburgh, Vasc Med Inst, Pittsburgh, PA USA.
[Bellavia, Landon; Kim-Shapiro, Daniel B.] Wake Forest Univ, Dept Phys, Winston Salem, NC 27109 USA.
[Bellavia, Landon; Kim-Shapiro, Daniel B.] Wake Forest Univ, Translat Sci Ctr, Winston Salem, NC 27109 USA.
[Bellavia, Landon] Univ Findlay, Dept Phys, Findlay, OH USA.
[Popovsky, Mark A.] Haemonet Corp, Braintree, MA USA.
RP Cortes-Puch, I (reprint author), NIH, Ctr Clin, Dept Crit Care Med, 10 Ctr Dr,Room 2C145, Bethesda, MD 20892 USA.
EM irene.cortes-puch@nih.gov
RI Kanias, Tamir/K-2384-2016
OI Kanias, Tamir/0000-0001-6558-0913
FU Haemonetics (Braintree, MA)
FX Haemonetics (Braintree, MA) funded 10% of the study costs and provided
the ACP215 (automated cell processing system) as well as the disposable
kits (RBC deglycerol set 325 mL BMB Ref. 236) used throughout the
experiments.
NR 51
TC 7
Z9 7
U1 0
U2 5
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 NOV
PY 2015
VL 55
IS 11
BP 2564
EP 2575
DI 10.1111/trf.13275
PG 12
WC Hematology
SC Hematology
GA CW3EZ
UT WOS:000364876100007
PM 26469998
ER
PT J
AU Flegel, WA
Gottschall, JL
Denomme, GA
AF Flegel, Willy A.
Gottschall, Jerome L.
Denomme, Gregory A.
TI Implementing mass-scale red cell genotyping at a blood center
SO TRANSFUSION
LA English
DT Article
ID APPLYING MOLECULAR IMMUNOHEMATOLOGY; DONORS; TIME; STRATEGY; PLATFORM;
ALLELES
AB BACKGROUNDWhen problems with compatibility beyond ABO and D arise, currently transfusion services search their inventories and perform time-consuming serologic testing to locate antigen-negative blood. These clinically important blood group antigens can be detected reliably by red cell genotyping, which is a technology whereby DNA-based techniques are used to evaluate gene polymorphisms that determine the expression of blood group antigens. We introduced mass-scale genotyping and measured availability of genotyped blood.
STUDY DESIGN AND METHODSAll non-Caucasian donors qualified for genotyping along with donors who had a history of repeat donation. Mass-scale red cell genotyping, performed on an electronic interfaced open array platform, was implemented to screen blood donors for 32 single-nucleotide polymorphisms that predicted 42 blood group antigens. Genotype screening results were confirmed by phenotyping, when needed for antigen-negative transfusion, before release of the red blood cell (RBC) unit.
RESULTSApproximately 22,000 donors were red cell genotyped within 4 months and a total of 43,066 donors in 4 years. There were 463 discordances (0.52% of 89,596 genotypes with a phenotype). Among the 307 resolved discordances, approximate equal numbers represented historical serologic or genotyping discrepancies (n=151 and n=156, respectively). In the final year of the study, a mean of 29% of the daily inventory had a genotype.
CONCLUSIONSRed cell genotyping of blood donors using an electronic interface created a large and stable supply of RBC units with historical genotypes. The database served the needs of antigen-negative blood requests for a large regional blood center and allowed us to abandon screening by serology.
C1 [Flegel, Willy A.] NIH, Ctr Clin, Dept Transfus Med, Bethesda, MD 20892 USA.
[Gottschall, Jerome L.] Med Coll Wisconsin, Dept Pathol, Milwaukee, WI USA.
[Gottschall, Jerome L.; Denomme, Gregory A.] BloodCtr Wisconsin, Diagnost Labs, Milwaukee, WI 53201 USA.
RP Denomme, GA (reprint author), BloodCtr Wisconsin, Diagnost Labs, 638 N 18th St,POB 2178, Milwaukee, WI 53201 USA.
EM greg.denomme@bcw.edu
OI Denomme, Gregory/0000-0001-8727-1679
FU BloodCenter of Wisconsin Diagnostic Laboratories Strategic Initiative;
NIH Clinical Center
FX This work was supported by a BloodCenter of Wisconsin Diagnostic
Laboratories Strategic Initiative and the Intramural Research Program of
the NIH Clinical Center.
NR 27
TC 5
Z9 5
U1 1
U2 1
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 NOV
PY 2015
VL 55
IS 11
BP 2610
EP 2615
DI 10.1111/trf.13168
PG 6
WC Hematology
SC Hematology
GA CW3EZ
UT WOS:000364876100013
PM 26094790
ER
PT J
AU Peters, JM
Gonzalez, FJ
Muller, R
AF Peters, Jeffrey M.
Gonzalez, Frank J.
Mueller, Rolf
TI Establishing the Role of PPAR beta/delta in Carcinogenesis
SO TRENDS IN ENDOCRINOLOGY AND METABOLISM
LA English
DT Review
ID ACTIVATED-RECEPTOR-BETA/DELTA; ANGIOPOIETIN-LIKE 4; CANCER-CELL-LINES;
PROMOTES VENOUS INVASION; COLON-CANCER; VASCULAR-PERMEABILITY;
EXPRESSION PATTERNS; SIGNALING PATHWAY; MICROARRAY DATA; RETINOIC ACID
AB The role of the nuclear hormone receptor peroxisome proliferator-activated receptor beta/delta (PPAR beta/delta) in carcinogenesis is controversial because conflicting studies indicate that it both inhibits and promotes tumorigenesis. In this review, we focus on recent studies on PPAR beta/delta including the significance of increased or decreased PPAR beta/delta expression in cancers; a range of opposing mechanisms describing how PPAR beta/delta agonists, antagonists, and inverse agonists regulate tumorigenesis and/or whether there may be cell context-specific mechanisms; and whether activating or inhibiting PPAR beta/delta is feasible for cancer chemoprevention and/or therapy. Research questions that need to be addressed are highlighted to establish whether PPAR beta/delta can be effectively targeted for cancer chemoprevention.
C1 [Peters, Jeffrey M.] Penn State Univ, Dept Vet & Biomed Sci, University Pk, PA 16802 USA.
[Peters, Jeffrey M.] Penn State Univ, Ctr Mol Toxicol & Carcinogenesis, University Pk, PA 16802 USA.
[Gonzalez, Frank J.] NCI, Lab Metab, Bethesda, MD 20892 USA.
[Mueller, Rolf] Univ Marburg, Ctr Tumor Biol & Immunol, Inst Mol Biol & Tumor Res, D-35043 Marburg, Germany.
RP Peters, JM (reprint author), Penn State Univ, Dept Vet & Biomed Sci, University Pk, PA 16802 USA.
EM jmp21@psu.edu
RI Muller, Rolf/L-4997-2016
OI Muller, Rolf/0000-0003-3339-4248
FU National Cancer Institute [CA124533, CA141029]; Intramural Research
Program of the National Institutes of Health [1ZIAB0005561,
1ZIABC005562, 1ZIABC005708]; Deutsche Forschungsgemeinschaft [MU601/13]
FX The authors gratefully acknowledge Till Adhikary for constructive
comments, and apologize to all scientists whose relevant work was not
cited owing to the space limitations of this review. This work was
supported by the National Cancer Institute grants CA124533, CA141029 to
J.M.P., by the Intramural Research Program of the National Institutes of
Health (1ZIAB0005561, 1ZIABC005562, 1ZIABC005708) to F.J.G., and a grant
from the Deutsche Forschungsgemeinschaft (MU601/13) to R.M.
NR 87
TC 8
Z9 8
U1 3
U2 10
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 NOV
PY 2015
VL 26
IS 11
BP 595
EP 607
DI 10.1016/j.tem.2015.09.004
PG 13
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA CW3LR
UT WOS:000364894300005
PM 26490384
ER
PT J
AU Birger, RB
Kouyos, RD
Cohen, T
Griffiths, EC
Huijben, S
Mina, MJ
Volkova, V
Grenfell, B
Metcalf, CJE
AF Birger, Ruthie B.
Kouyos, Roger D.
Cohen, Ted
Griffiths, Emily C.
Huijben, Silvie
Mina, Michael J.
Volkova, Victoriya
Grenfell, Bryan
Metcalf, C. Jessica E.
TI The potential impact of coinfection on antimicrobial chemotherapy and
drug resistance (vol 23, pg 537, 2015)
SO TRENDS IN MICROBIOLOGY
LA English
DT Correction
C1 [Birger, Ruthie B.; Mina, Michael J.; Grenfell, Bryan; Metcalf, C. Jessica E.] Princeton Univ, Dept Ecol & Evolutionary Biol, Princeton, NJ 08544 USA.
[Kouyos, Roger D.] Univ Zurich, Univ Zurich Hosp, Div Infect Dis & Hosp Epidemiol, Zurich, Switzerland.
[Kouyos, Roger D.] Univ Zurich, Inst Med Virol, Zurich, Switzerland.
[Cohen, Ted] Yale Univ, Sch Publ Hlth, Dept Epidemiol Microbial Dis, New Haven, CT USA.
[Griffiths, Emily C.] N Carolina State Univ, Dept Entomol, Raleigh, NC 27695 USA.
[Huijben, Silvie] Univ Barcelona, Hosp Clin, Barcelona Ctr Int Hlth Res CRESIB, ISGlobal, Barcelona, Spain.
[Mina, Michael J.] Emory Univ, Sch Med, Med Scientist Training Program, Atlanta, GA USA.
[Volkova, Victoriya] Kansas State Univ, Coll Vet Med, Inst Computat Comparat Med, Dept Diagnost Med Pathobiol, Manhattan, KS 66506 USA.
[Grenfell, Bryan; Metcalf, C. Jessica E.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Birger, RB (reprint author), Princeton Univ, Dept Ecol & Evolutionary Biol, Princeton, NJ 08544 USA.
EM rbirger@princeton.edu
NR 1
TC 0
Z9 0
U1 1
U2 5
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0966-842X
EI 1878-4380
J9 TRENDS MICROBIOL
JI Trends Microbiol.
PD NOV
PY 2015
VL 23
IS 11
BP 742
EP 742
DI 10.1016/j.tim.2015.09.001
PG 1
WC Biochemistry & Molecular Biology; Microbiology
SC Biochemistry & Molecular Biology; Microbiology
GA CW3IA
UT WOS:000364884200009
ER
PT J
AU Brenner, P
Mayr, T
Guethoff, S
Buchholz, S
Poettinger, T
Lutzmann, I
Werner, F
Bauer, A
Klymiuk, N
Wolf, E
Reimann, K
Mohiuddin, M
Hermanns, W
Ayares, D
McGregor, C
Lambris, JD
Hagl, C
Reichart, B
Abicht, JM
AF Brenner, Paolo
Mayr, Tanja
Guethoff, Sonja
Buchholz, Stefan
Poettinger, Thomas
Lutzmann, Isabelle
Werner, Fabian
Bauer, Andreas
Klymiuk, Nikolai
Wolf, Eckhard
Reimann, Keith
Mohiuddin, Muhammad
Hermanns, Walter
Ayares, David
McGregor, Christopher
Lambris, John D.
Hagl, Christian
Reichart, Bruno
Abicht, Jan-Michael
TI CD40mAb costimulation blockade in (life-supporting) heterotopic and
orthotopic cardiac xenotransplantation models with GalT-KO/hCD46/hTM
transgenic donor pigs into the baboon
SO XENOTRANSPLANTATION
LA English
DT Meeting Abstract
CT IPITA/IXA/CTS Joint Congress
CY NOV 15-19, 2015
CL Melbourne, AUSTRALIA
SP IPITA, IXA, CTS
C1 [Brenner, Paolo; Mayr, Tanja; Guethoff, Sonja; Buchholz, Stefan; Poettinger, Thomas; Lutzmann, Isabelle; Werner, Fabian; Hagl, Christian] Univ Munich, Dept Cardiac Surg, Munich, Germany.
[Brenner, Paolo; Mayr, Tanja; Guethoff, Sonja; Poettinger, Thomas; Lutzmann, Isabelle; Werner, Fabian; Reichart, Bruno; Abicht, Jan-Michael] Univ Munich, Walter Brendel Ctr, Munich, Germany.
[Bauer, Andreas; Abicht, Jan-Michael] Univ Munich, Dept Anaesthesiol, Munich, Germany.
[Klymiuk, Nikolai; Wolf, Eckhard] Univ Munich, Dept Mol Anim Breeding & Biotechnol, Munich, Germany.
[Reimann, Keith] Univ Massachusetts, Sch Med, MassBiol, Boston, MA 02125 USA.
[Mohiuddin, Muhammad] NHLBI, Cardiothorac Surg Res Lab, NIH, Bethesda, WA USA.
[Hermanns, Walter] Univ Munich, Dept Vet Pathol, Munich, Germany.
[Ayares, David] Revivicor Inc, Blacksburg, VA USA.
[McGregor, Christopher] UCL, Dept Cardiothorac Surg, London, England.
[Lambris, John D.] Univ Penn, Pathol & Lab Med, Philadelphia, PA 19104 USA.
RI Mohiuddin, Muhammad/M-4642-2013
OI Mohiuddin, Muhammad/0000-0003-4654-783X
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0908-665X
EI 1399-3089
J9 XENOTRANSPLANTATION
JI Xenotransplantation
PD NOV
PY 2015
VL 22
SU 1
SI SI
MA 815
BP S146
EP S146
PG 1
WC Medicine, Research & Experimental; Transplantation
SC Research & Experimental Medicine; Transplantation
GA CV9FY
UT WOS:000364594100351
ER
PT J
AU Miller, J
Singh, A
Eckhaus, M
Corcoran, P
Thomas, M
Lewis, B
Reimann, K
Ayares, D
Horvath, K
Mohiuddin, M
AF Miller, Justin
Singh, Avneesh
Eckhaus, Michael
Corcoran, Philip
Thomas, Marvin
Lewis, Billeta
Reimann, Keith
Ayares, David
Horvath, Keith
Mohiuddin, Muhammad
TI Histological evidence of acute rejection after terminating anti CD40
antibody (2C10R4) treatment in GTKO.hCD46.htbm pig to baboon cardiac
xenografts surviving for over one year
SO XENOTRANSPLANTATION
LA English
DT Meeting Abstract
CT IPITA/IXA/CTS Joint Congress
CY NOV 15-19, 2015
CL Melbourne, AUSTRALIA
SP IPITA, IXA, CTS
C1 [Miller, Justin; Singh, Avneesh; Corcoran, Philip; Horvath, Keith; Mohiuddin, Muhammad] NHLBI, Cardiothorac Surg Res Program, NIH, Bethesda, MD 20892 USA.
[Eckhaus, Michael; Thomas, Marvin; Lewis, Billeta] NIH, Div Vet Resources ORS, Bethesda, MD 20892 USA.
[Reimann, Keith] Univ Massachusetts, Boston, MD USA.
[Ayares, David] Revivicor Inc, Blacksburg, VA USA.
RI Mohiuddin, Muhammad/M-4642-2013
OI Mohiuddin, Muhammad/0000-0003-4654-783X
NR 0
TC 1
Z9 1
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0908-665X
EI 1399-3089
J9 XENOTRANSPLANTATION
JI Xenotransplantation
PD NOV
PY 2015
VL 22
SU 1
SI SI
MA 811
BP S145
EP S145
PG 1
WC Medicine, Research & Experimental; Transplantation
SC Research & Experimental Medicine; Transplantation
GA CV9FY
UT WOS:000364594100347
ER
PT J
AU Mohiuddin, M
Singh, A
Corcoran, P
Thomas, M
Lewis, B
Clark, T
Eckhaus, M
Belli, A
Reimann, K
Klymuik, N
Wolf, E
Ayares, D
Horvath, K
AF Mohiuddin, Muhammad
Singh, Avneesh
Corcoran, Philip
Thomas, Marvin
Lewis, Billeta
Clark, Tannia
Eckhaus, Michael
Belli, Aaron
Reimann, Keith
Klymuik, Nikolai
Wolf, Eckhard
Ayares, David
Horvath, Keith
TI Critical need of continuous co-stimulation blockade with anti CD40
antibody (2C10.R4) for long-term maintenance of GTKO.HCD46.hTBM pig
cardiac xenograft survival in baboons
SO XENOTRANSPLANTATION
LA English
DT Meeting Abstract
CT IPITA/IXA/CTS Joint Congress
CY NOV 15-19, 2015
CL Melbourne, AUSTRALIA
SP IPITA, IXA, CTS
C1 [Mohiuddin, Muhammad; Singh, Avneesh; Corcoran, Philip; Horvath, Keith] NHLBI, Cardiothorac Surg Res Program, NIH, Bethesda, MD 20892 USA.
[Thomas, Marvin; Lewis, Billeta; Clark, Tannia; Eckhaus, Michael] NIH, DVR ORS, Bethesda, MD 20892 USA.
[Belli, Aaron; Reimann, Keith] Univ Massachusetts, Boston, MA 02125 USA.
[Klymuik, Nikolai; Wolf, Eckhard] LMU, Munich, Germany.
[Ayares, David] Revivicor Inc, Blacksburg, VA USA.
RI Mohiuddin, Muhammad/M-4642-2013
OI Mohiuddin, Muhammad/0000-0003-4654-783X
NR 0
TC 1
Z9 1
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0908-665X
EI 1399-3089
J9 XENOTRANSPLANTATION
JI Xenotransplantation
PD NOV
PY 2015
VL 22
SU 1
SI SI
MA 810
BP S144
EP S145
PG 2
WC Medicine, Research & Experimental; Transplantation
SC Research & Experimental Medicine; Transplantation
GA CV9FY
UT WOS:000364594100346
ER
PT J
AU Singh, A
Corcoran, P
Lewis, B
Thomas, M
Ayares, D
Horvath, K
Mohiuddin, M
AF Singh, Avneesh
Corcoran, Philip
Lewis, Billeta
Thomas, Marvin
Ayares, David
Horvath, Keith
Mohiuddin, Muhammad
TI Cardiac xenotransplantation: role of CD4+CD25hiFoxP3+T regulatory cells
in long-term cardiac xenograft survivors
SO XENOTRANSPLANTATION
LA English
DT Meeting Abstract
CT IPITA/IXA/CTS Joint Congress
CY NOV 15-19, 2015
CL Melbourne, AUSTRALIA
SP IPITA, IXA, CTS
C1 [Singh, Avneesh; Corcoran, Philip; Horvath, Keith; Mohiuddin, Muhammad] NHLBI, Cardiothorac Surg Res Program, NIH, Bethesda, MD 20892 USA.
[Lewis, Billeta; Thomas, Marvin] NIH, DVR, ORS, Bethesda, MD 20892 USA.
[Ayares, David] Revivicor Inc, Blacksburg, VA USA.
RI Mohiuddin, Muhammad/M-4642-2013
OI Mohiuddin, Muhammad/0000-0003-4654-783X
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0908-665X
EI 1399-3089
J9 XENOTRANSPLANTATION
JI Xenotransplantation
PD NOV
PY 2015
VL 22
SU 1
SI SI
MA 1058
BP S196
EP S196
PG 1
WC Medicine, Research & Experimental; Transplantation
SC Research & Experimental Medicine; Transplantation
GA CV9FY
UT WOS:000364594100481
ER
PT J
AU Singh, A
Corcoran, P
Lewis, B
Thomas, M
Ayares, D
Horvath, K
Mohiuddin, M
AF Singh, Avneesh
Corcoran, Philip
Lewis, Billeta
Thomas, Marvin
Ayares, David
Horvath, Keith
Mohiuddin, Muhammad
TI Cardiac xenotransplantation: Re-emerged b cells after transient
depletion by Rituxan treatment maintains their repertoire but have a
muted immune response
SO XENOTRANSPLANTATION
LA English
DT Meeting Abstract
CT IPITA/IXA/CTS Joint Congress
CY NOV 15-19, 2015
CL Melbourne, AUSTRALIA
SP IPITA, IXA, CTS
C1 [Singh, Avneesh; Corcoran, Philip; Horvath, Keith; Mohiuddin, Muhammad] NHLBI, Cardiothorac Surg Res Program, NIH, Bethesda, MD 20892 USA.
[Lewis, Billeta; Thomas, Marvin] NIH, DvR ORS, Bethesda, MD 20892 USA.
[Ayares, David] Revivicor Inc, Blacksburg, VA USA.
RI Mohiuddin, Muhammad/M-4642-2013
OI Mohiuddin, Muhammad/0000-0003-4654-783X
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0908-665X
EI 1399-3089
J9 XENOTRANSPLANTATION
JI Xenotransplantation
PD NOV
PY 2015
VL 22
SU 1
SI SI
MA 812
BP S145
EP S145
PG 1
WC Medicine, Research & Experimental; Transplantation
SC Research & Experimental Medicine; Transplantation
GA CV9FY
UT WOS:000364594100348
ER
PT J
AU Dauter, Z
Wlodawer, A
AF Dauter, Zbigniew
Wlodawer, Alexander
TI On the accuracy of unit-cell parameters in protein crystallography
SO ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY
LA English
DT Article
DE protein crystallography; unit-cell parameter accuracy; symmetry
ID CRYSTAL-STRUCTURE; DIFFRACTION DATA; RADIATION-DAMAGE; STRUCTURAL BASIS;
BINDING; INSIGHTS; DIMER; CRYOCRYSTALLOGRAPHY; REFINEMENT; PEPTIDE
AB The availability in the Protein Data Bank (PDB) of a number of structures that are presented in space group P1 but in reality possess higher symmetry allowed the accuracy and precision of the unit-cell parameters of the crystals of macromolecules to be evaluated. In addition, diffraction images from crystals of several proteins, previously collected as part of in-house projects, were processed independently with three popular software packages. An analysis of the results, augmented by published serial crystallography data, suggests that the apparent precision of the presentation of unit-cell parameters in the PDB to three decimal points is not justified, since these parameters are subject to errors of not less than 0.2%. It was also noticed that processing data including full crystallographic symmetry does not lead to deterioration of the refinement parameters; thus, it is not beneficial to treat the crystals as belonging to space group P1 when higher symmetry can be seen.
C1 [Dauter, Zbigniew] NCI, Synchrotron Radiat Res Sect, MCL, Argonne Natl Lab, Argonne, IL 60439 USA.
[Wlodawer, Alexander] NCI, Prot Struct Sect, MCL, Ft Detrick, MD 21702 USA.
RP Dauter, Z (reprint author), NCI, Synchrotron Radiat Res Sect, MCL, Argonne Natl Lab, Argonne, IL 60439 USA.
EM dauter@anl.gov; wlodawer@nih.gov
FU Intramural Research Program of National Cancer Institute, Center for
Cancer Research
FX This work was supported by the Intramural Research Program of the
National Cancer Institute, Center for Cancer Research.
NR 42
TC 0
Z9 0
U1 0
U2 6
PU INT UNION CRYSTALLOGRAPHY
PI CHESTER
PA 2 ABBEY SQ, CHESTER, CH1 2HU, ENGLAND
SN 2059-7983
J9 ACTA CRYSTALLOGR D
JI Acta Crystallogr. Sect. D-Struct. Biol.
PD NOV
PY 2015
VL 71
BP 2217
EP 2226
DI 10.1107/S1399004715015503
PN 11
PG 10
WC Biochemical Research Methods; Biochemistry & Molecular Biology;
Biophysics; Crystallography
SC Biochemistry & Molecular Biology; Biophysics; Crystallography
GA CV8QT
UT WOS:000364553500005
PM 26527139
ER
PT J
AU Jakob, M
Lubkowski, J
O'Keefe, BR
Wlodawer, A
AF Jakob, Michal
Lubkowski, Jacek
O'Keefe, Barry R.
Wlodawer, Alexander
TI Structure of a lectin from the sea mussel Crenomytilus grayanus (CGL)
SO ACTA CRYSTALLOGRAPHICA SECTION F-STRUCTURAL BIOLOGY COMMUNICATIONS
LA English
DT Article
DE lectin; molecular replacement; carbohydrate binding; structure
comparison; beta-trefoil
ID GALNAC/GAL-SPECIFIC LECTIN; AMINO-ACID-SEQUENCE; MOLECULAR REPLACEMENT;
PROTEIN-STRUCTURE; PREDICTION; CLONING; SUITE
AB CGL is a 150 amino-acid residue lectin that was originally isolated from the sea mussel Crenomytilus grayanus. It is specific for binding GalNAc/Gal-containing carbohydrate moieties and in general does not share sequence homology with other known galectins or lectins. Since CGL displays antibacterial, antifungal and antiviral activities, and interacts with high affinity with mucin-type receptors, which are abundant on some cancer cells, knowledge of its structure is of significant interest. Conditions have been established for the expression, purification and crystallization of a recombinant variant of CGL. The crystal structure of recombinant CGL was determined and refined at a resolution of 2.12 angstrom. The amino-acid sequence of CGL contains three homologous regions (73% similarity) and the folded protein has a beta-trefoil topology. Structural comparison of CGL with the closely related lectin MytiLec allowed description of the glycan-binding pockets.
C1 [Jakob, Michal; Lubkowski, Jacek; Wlodawer, Alexander] NCI, Macromol Crystallog Lab, Ctr Canc Res, Frederick, MD 21702 USA.
[Jakob, Michal; O'Keefe, Barry R.] NCI, Mol Targets Lab, Ctr Canc Res, Frederick, MD 21702 USA.
[O'Keefe, Barry R.] NCI, Nat Prod Branch, Dev Therapeut Program, Div Canc Treatment & Diag, Frederick, MD 21702 USA.
RP Wlodawer, A (reprint author), NCI, Macromol Crystallog Lab, Ctr Canc Res, Frederick, MD 21702 USA.
EM wlodawer@nih.gov
FU US Department of Energy, Office of Science, Office of Basic Energy
Sciences [W-31-109-Eng-38]; Intramural Research Program of the NIH,
National Cancer Institute, Center for Cancer Research; NIH Intramural
AIDS Targeted Antiviral Program
FX We would like to thank Mr Mi Li for assistance with X-ray data
collection. We acknowledge the use of beamline 22-ID of the Southeast
Regional Collaborative Access Team (SERCAT) located at the Advanced
Photon Source, Argonne National Laboratory. Use of the Advanced Photon
Source was supported by the US Department of Energy, Office of Science,
Office of Basic Energy Sciences under Contract No. W-31-109-Eng-38. This
work was supported in part by the Intramural Research Program of the
NIH, National Cancer Institute, Center for Cancer Research and in part
by funds from the NIH Intramural AIDS Targeted Antiviral Program (to AW,
BRO and MJ).
NR 28
TC 4
Z9 4
U1 1
U2 5
PU INT UNION CRYSTALLOGRAPHY
PI CHESTER
PA 2 ABBEY SQ, CHESTER, CH1 2HU, ENGLAND
SN 2053-230X
J9 ACTA CRYSTALLOGR F
JI Acta Crystallogr. F-Struct. Biol. Commun.
PD NOV
PY 2015
VL 71
BP 1429
EP 1436
DI 10.1107/S2053230X15019858
PN 11
PG 8
WC Biochemical Research Methods; Biochemistry & Molecular Biology;
Biophysics; Crystallography
SC Biochemistry & Molecular Biology; Biophysics; Crystallography
GA CV8SJ
UT WOS:000364557700011
PM 26527272
ER
PT J
AU Hiruy, H
Fuchs, EJ
Marzinke, MA
Bakshi, RP
Breakey, JC
Aung, WS
Manohar, M
Yue, C
Caffo, BS
Du, Y
Abebe, KZ
Spiegel, HML
Rohan, LC
McGowan, I
Hendrix, CW
AF Hiruy, Hiwot
Fuchs, Edward J.
Marzinke, Mark A.
Bakshi, Rahul P.
Breakey, Jennifer C.
Aung, Wutyi S.
Manohar, Madhuri
Yue, Chen
Caffo, Brian S.
Du, Yong
Abebe, Kaleab Z.
Spiegel, Hans M. L.
Rohan, Lisa C.
McGowan, Ian
Hendrix, Craig W.
TI A Phase 1 Randomized, Blinded Comparison of the Pharmacokinetics and
Colonic Distribution of Three Candidate Rectal Microbicide Formulations
of Tenofovir 1% Gel with Simulated Unprotected Sex (CHARM-02)
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Article
ID ANTIRETROVIRAL PROPHYLAXIS; HIV TRANSMISSION; ORAL TENOFOVIR; MEN;
PREVENTION; EPIDEMIC; ACCEPTABILITY; HYPEROSMOLAR; PREVALENCE;
SURROGATES
AB CHARM-02 is a crossover, double-blind, randomized trial to compare the safety and pharmacokinetics of three rectally applied tenofovir 1% gel candidate rectal microbicides of varying osmolalities: vaginal formulation (VF) (3111 mOsmol/kg), the reduced glycerin vaginal formulation (RGVF) (836 mOsmol/kg), and an isoosmolal rectal-specific formulation (RF) (479 mOsmol/kg). Participants (n = 9) received a single, 4 ml, radiolabeled dose of each gel twice, once with and once without simulated unprotected receptive anal intercourse (RAI). The safety, plasma tenofovir pharmacokinetics, colonic small molecule permeability, and SPECT/CT imaging of lower gastrointestinal distribution of drug and virus surrogate were assessed. There were no Grade 3 or 4 adverse events reported for any of the products. Overall, there were more Grade 2 adverse events in the VF group compared to RF (p = 0.006) and RGVF (p = 0.048). In the absence of simulated unprotected RAI, VF had up to 3.8-fold greater systemic tenofovir exposure, 26- to 234-fold higher colonic permeability of the drug surrogate, and 1.5- to 2-fold greater proximal migration in the colonic lumen, when compared to RF and RGVF. Similar trends were observed with simulated unprotected RAI, but most did not reach statistical significance. SPECT analysis showed 86% (standard deviation 19%) of the drug surrogate colocalized with the virus surrogate in the colonic lumen. There were no significant differences between the RGVF and RF formulation, with the exception of a higher plasma tenofovir concentration of RGVF in the absence of simulated unprotected RAI. VF had the most adverse events, highest plasma tenofovir concentrations, greater mucosal permeability of the drug surrogate, and most proximal colonic luminal migration compared to RF and RGVF formulations. There were no major differences between RF and RGVF formulations. Simultaneous assessment of toxicity, systemic and luminal pharmacokinetics, and colocalization of drug and viral surrogates substantially informs rectal microbicide product development.
C1 [Hiruy, Hiwot; Fuchs, Edward J.; Marzinke, Mark A.; Bakshi, Rahul P.; Breakey, Jennifer C.; Aung, Wutyi S.; Manohar, Madhuri; Yue, Chen; Hendrix, Craig W.] Johns Hopkins Univ, Dept Med Clin Pharmacol, Baltimore, MD 21287 USA.
[Yue, Chen; Caffo, Brian S.] Johns Hopkins Sch Publ Hlth, Dept Biostat, Baltimore, MD USA.
[Du, Yong] Johns Hopkins Sch Med, Dept Radiol, Baltimore, MD USA.
[Abebe, Kaleab Z.; Rohan, Lisa C.; McGowan, Ian] Univ Pittsburgh, Dept Med, Pittsburgh, PA USA.
[Spiegel, Hans M. L.] NIAID, HJF DAIDS, NIH, US Dept HHS, Bethesda, MD 20892 USA.
[Rohan, Lisa C.; McGowan, Ian] Magee Womens Res Inst, Pittsburgh, PA USA.
RP Hendrix, CW (reprint author), Johns Hopkins Univ, Sch Med, 600 North Wolfe St,Blalock 569, Baltimore, MD 21287 USA.
EM chendrix@jhmi.edu
RI Hendrix, Craig/G-4182-2014;
OI Hendrix, Craig/0000-0002-5696-8665; Abebe, Kaleab/0000-0002-3644-8419;
Bakshi, Rahul/0000-0003-1478-1031
FU U19 grant under the Integrated Preclinical-Clinical Program for HV
Topical Microbicides (IPCP-HTM), Division of AIDS, National Institute of
Allergy and Infectious Diseases, National Institutes of Health (NIH)
[AI082637]; National Institute of Allergies and Infectious Diseases,
National Institutes of Health, Department of Health and Human Services
[HHSN272200800014C]
FX The study was funded by a U19 grant under the Integrated
Preclinical-Clinical Program for HV Topical Microbicides (IPCP-HTM),
Division of AIDS, National Institute of Allergy and Infectious Diseases,
National Institutes of Health (NIH) (AI082637). This project has also
been funded in part with federal funds from the National Institute of
Allergies and Infectious Diseases, National Institutes of Health,
Department of Health and Human Services, under contract no.
HHSN272200800014C.
NR 36
TC 3
Z9 3
U1 0
U2 0
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0889-2229
EI 1931-8405
J9 AIDS RES HUM RETROV
JI Aids Res. Hum. Retrovir.
PD NOV 1
PY 2015
VL 31
IS 11
BP 1098
EP 1108
DI 10.1089/aid.2015.0098
PG 11
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA CV5SJ
UT WOS:000364331100006
PM 26227279
ER
PT J
AU Weinberg, A
Muresan, P
Richardson, K
Fenton, T
Dominguez, T
Bloom, A
Watts, DH
Abzug, MJ
Nachman, SA
Levin, MJ
AF Weinberg, Adriana
Muresan, Petronella
Richardson, Kelly
Fenton, Terence
Dominguez, Teresa
Bloom, Anthony
Watts, D. Heather
Abzug, Mark J.
Nachman, Sharon A.
Levin, Myron J.
CA P1086 Study Team
TI Heterogeneity of T Cell Responses to Pandemic pH1N1 Monovalent Vaccine
in HIV-Infected Pregnant Women
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Article
ID INACTIVATED INFLUENZA VACCINES; VIRUS-INFECTION; ANTIBODY-RESPONSES;
PROTECTION; SAFETY; CHILDREN; IMMUNOGENICITY; CORRELATE; ADULTS;
ASSOCIATION
AB We investigated the Th1 protective and regulatory T and B cell (Treg and Breg) responses to pH1N1 monovalent influenza vaccine (IIV1) in HIV-infected pregnant women on combination antiretroviral therapy (cART). Peripheral blood mononuclear cells (PBMCs) from 52 study participants were cryopreserved before and after vaccination and analyzed by flow cytometry. pH1N1-specific Th1, Treg, and Breg responses were measured in PBMCs after in vitro stimulation with pH1N1 and control antigen. The cohort analysis did not detect changes in pH1N1-Th1, Treg, or Breg subsets postvaccination. However, individual analyses distinguished subjects who mounted vigorous Th1 responses postvaccination from others who did not. Postvaccination, high pH1N1-Th1 correlated with high pH1N1-Treg and Breg responses, suggesting that low influenza effector responses did not result from excessive vaccine-induced immune regulation. High postvaccination pH1N1-Th1 responses correlated with baseline high PHA- and pH1N1-IFN-gamma ELISpot and circulating CD4(+)CD39(+)% and CD8(+)CD39(+)% Treg, with low CD8(+) cell numbers and CD19(+)FOXP3(+)% Breg, but not with CD4(+) cell numbers or HIV viral load. These data highlight the heterogeneity of T cell responses to vaccines in HIV-infected individuals on cART. Predictors of robust Th1 responses to IIV include CD8(+) cell numbers, T cell functionality, and circulating Breg and Treg.
C1 [Weinberg, Adriana; Richardson, Kelly; Dominguez, Teresa; Abzug, Mark J.; Levin, Myron J.] Univ Colorado Anschutz Med Campus, Aurora, CO USA.
[Muresan, Petronella; Fenton, Terence] Harvard Univ, Sch Publ Hlth, Stat & Data Anal Ctr, Ctr Biostat AIDS Res, Boston, MA 02115 USA.
[Bloom, Anthony] Frontier Sci & Technol Res Fdn Inc, Buffalo, NY USA.
[Watts, D. Heather] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Maternal & Pediat Infect Dis Branch, Bethesda, MD USA.
[Nachman, Sharon A.] SUNY Stony Brook, Hlth Sci Ctr Stony Brook, Stony Brook, NY 11794 USA.
RP Weinberg, A (reprint author), Mail Stop 8604,12700 East 19th Ave,Room 11126, Aurora, CO 80045 USA.
EM adriana.weinberg@ucdenver.edu
FU NIH/NCATS Colorado CTSI Grant [UL1 TR000154]; National Institute of
Allergy and Infectious Diseases (NIAID) [U01 AI068632]; Eunice Kennedy
Shriver National Institute of Child Health and Human Development
(NICHD); National Institute of Mental Health (NIMH) [AI068632]; National
Institute of Allergy and Infectious Diseases (NIAID); NICHD
International and Domestic Pediatric and Maternal HIV Clinical Trials
Network - NICHD [N01-DK-9-001/HHSN267200800001C]; [N01HD33162 (97-07)]
FX Participating sites and site personnel: University of Miami
Pediatric/Perinatal HIV/AIDS CRS (Amanda Cotter, MD; Gwendolyn B. Scott,
MD; Erika Lopez-Bertiery, MD; Safia Khan, MD); University of Puerto Rico
Pediatric HIV/AIDS Research Program CRS (Irma L. Febo, MD; Carmen D.
Zorrilla, MD; Vivian Tamayo-Agrait, MD; Ruth Santos, RN, MPH);
University of Southern California, LA NICHD CRS (Alice Stek, MD; Michael
Neely, MD; LaShonda Spencer, MD; Andrea Kovacs, MD); Washington Hospital
Center NICHD CRS (Sara Parker, MD; Patricia Tanjutco, MD; Vanessa
Emmanuel, BA; Liv Thulin); Texas Children's Hospital CRS (Shelly
Buschur, RN, CNM; Mary Paul, MD; Filiz Seeborg, MD; Kathy Pitts, PhD);
Chicago Children's CRS (Jessica Shore, RN; Sarah Sutton, MD); UCSD
Maternal, Child, and Adolescent HIV CRS (Stephen A. Spector, MD; Andrew
Hull, MD; Mary Caffery, RN, MSN; Jean Manning, RN, BSN); DUMC Pediatric
CRS (Margaret Donnelly, PA; Mary Jo Hassett, RN; Elizabeth Livingston,
MD; Julieta Giner, RN); Rush University Cook County Hospital, Chicago
NICHD CRS (Mariam Aziz, MD; Latania Logan, MD; Julie Schmidt, MD; Helen
Cejtin, MD); The Children's Hospital of Philadelphia IMPAACT CRS (Samuel
Parry, MD; Rita Leite, MD); University of South Florida, Tampa NICHD CRS
(Karen L. Bruder, MD; Gail Lewis, RN; Patricia Emmanuel, MD; Tampa
General Hospital); San Juan City Hospital PR NICHD CRS (Elvia Perez,
MPH, MA; Rodrigo Diaz, MD; Dalila Guzman, RPh; Midnela Acevedo-Flores,
MD); South Florida CDC, Ft. Lauderdale NICHD CRS; Johns Hopkins
University, Baltimore NCHD CRS (Allison Agwu, MD, ScM; Todd Noletto,
MPH; Jennifer Chang, BS; Andi Weiss, PharmD); Tulane University, New
Orleans NICHD CRS (Chi Dola, MD; Thomas Alchediak, MD; Yvette Luster,
RN; Sheila Bradford, RN); Bronx-Lebanon Hospital IMPAACT CRS (Jenny
Gutierrez, MD; Mahboobullah Mirza Baig, MD; Stefan Hagmann, MD; Murli
Purswani, MD); NJ Medical School CRS (Arlene D. Bardeguez, MD, MPH;
Charmane Calilap-Bernardo, RN; Linda Bettica, RN); Columbia IMPAACT CRS
(Andrea Jurgrau, CNP; Gina Silva, RN; Alice Higgins, RN; Marc Foca, MD);
Metropolitan Hospital NICHD CRS (Mahrukh Bamji, MD; Santa Paul, MD;
Siobhan Riley, MPH; Deepali Jain, MD); Children's Hospital of Boston
NICHD CRS (Sandra K. Burchett, MD, MS; Ruth Tuomala, MD; Arlene Buck,
RN; Catherine Kneut, RN, CPNP); University of Colorado, Denver NICHD CRS
(Jennifer Dunn, FNP-C; Paul Harding, MS; Kay Kinzie, FNP-C; Jenna
Wallace, MSW; Supported by NIH/NCATS Colorado CTSI Grant Number UL1
TR000154); St. Jude/UTHSC CRS (L. Jill Utech, RN, MSN, CCRP; Edwin
Thorpe, Jr., MD; Nina Sublette, RN, FNP, PhD; Pam Finnie, MSN); WNE
Maternal Pediatric Adolescent AIDS CRS; UCLA-Los Angeles/Brazil AIDS
Consortium (LABAC) CRS (Jaime G. Deville, MD; Karin Nielsen-Saines, MD;
Nicole Falgout, RN; Joseph Geffen); Boston Medical Center Pediatric HIV
Program NICHD CRS; Jacobi Medical Center Bronx NICHD CRS; Seattle
Children's Hospital CRS; SUNY Stony Brook NICHD CRS (Denise Ferraro,
FNP; Erin Infanzon; Michele Kelly, NP; Jennifer Griffin, CNM); Miller
Children's Hospital Long Beach, CA NICHD CRS (Audra Deveikis, MD;
Janielle Jackson-Alvarez, RN; Tempe K. Chen, MD; Jagmohan S. Batra, MD);
University of Florida College of Medicine, Jacksonville NICHD CRS
(Mobeen Rathore, MD; Ayesha Mirza, MD; Nizar Maraqa, MD; Kathleen Thoma,
MA, CCRP); University of California, San Francisco NICHD CRS Diane Wara,
MD; Nicole Tilton, PNP; Mica Muscat, PNP).; Overall support for the
International Maternal Pediatric Adolescent AIDS Clinical Trials Group
(IMPAACT) was provided by the National Institute of Allergy and
Infectious Diseases (NIAID) [U01 AI068632], the Eunice Kennedy Shriver
National Institute of Child Health and Human Development (NICHD), and
the National Institute of Mental Health (NIMH) [AI068632]. Support of
the sites was provided by the National Institute of Allergy and
Infectious Diseases (NIAID) and the NICHD International and Domestic
Pediatric and Maternal HIV Clinical Trials Network funded by NICHD
(contract number N01-DK-9-001/HHSN267200800001C). The laboratory work
was supported by N01HD33162 (97-07) and the statistical work by the
Statistical and Data Analysis Center at Harvard School of Public Health
under the National Institute of Allergy and Infectious Diseases
cooperative agreement #5 U01 AI41110 with the Pediatric AIDS Clinical
Trials Group (PACTG) and #1 U01 AI068616 with the IMPAACT Group. The
contents of this publication are solely the responsibility of the
authors and do not necessarily represent the official views of the NIH,
the United States Government, or the U.S. Department of State.
NR 31
TC 0
Z9 0
U1 0
U2 0
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0889-2229
EI 1931-8405
J9 AIDS RES HUM RETROV
JI Aids Res. Hum. Retrovir.
PD NOV 1
PY 2015
VL 31
IS 11
BP 1170
EP 1177
DI 10.1089/aid.2015.0151
PG 8
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA CV5SJ
UT WOS:000364331100014
PM 26322930
ER
PT J
AU Sarafin, K
Durazo-Arvizu, R
Tian, L
Phinney, KW
Tai, S
Camara, JE
Merkel, J
Green, E
Sempos, CT
Brooks, SPJ
AF Sarafin, Kurtis
Durazo-Arvizu, Ramon
Tian, Lu
Phinney, Karen W.
Tai, Susan
Camara, Johanna E.
Merkel, Joyce
Green, Evan
Sempos, Christopher T.
Brooks, Stephen P. J.
TI Standardizing 25-hydroxyvitamin D values from the Canadian Health
Measures Survey
SO AMERICAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Article
DE standardization; vitamin D; immunoassay; population survey; adequacy;
CHMS
ID TANDEM MASS-SPECTROMETRY; VITAMIN-D INSUFFICIENCY; D ASSAYS; CIRCULATING
25-HYDROXYVITAMIN-D; D METABOLITES; HUMAN SERUM; ACCURACY; D-3
AB Background: The Canadian Health Measures Survey (CHMS) is an ongoing cross-sectional national survey that includes a measure of 25-hydroxyvitamin D [25(OH)D] by immunoassay. For cycles 1 and 2, the collection period occurred approximately every 2 y, with a new sample of similar to 5600 individuals.
Objective: The goal was to standardize the original 25(OH)D CHMS values in cycles 1 and 2 to the internationally recognized reference measurement procedures (RMPs) developed by the US National Institute for Standards and Technology (NIST) and Ghent University, Belgium.
Design: Standardization was accomplished by using a 2-step procedure. First, serum samples corresponding to the original plasma samples were remeasured by using the currently available immunoassay method. Second, 50 serum samples with known 25(OH)D values assigned by the NIST and Ghent reference method laboratories were measured by using the currently available immunoassay method. The mathematical models for each step-i.e., 1) Y-Current = X-Original and 2) YNIST-Ghent = X-Current -were estimated by using Deming regression, and the 2 models were solved to obtain a single equation for converting the "original" values to NIST-Ghent RMP values.
Results: After standardization (cycles 1 and 2 combined), the percentage of Canadians with 25(OH)D values <40 nmol/L increased from 16.4% (original) to 19.4% (standardized), and values <50 nmol/L increased from 29.0% (original) to 36.8% (standardized). The 25(OH)D standardized distributions (cycles 1 and 2 analyzed separately) were similar across age and sex groups; slightly higher values were associated with cycle 2 in the young and old. This finding contrasts with the original data, which indicated that cycle 2 values were lower for all age groups.
Conclusion: The shifts in 25(OH)D distribution brought about by standardization indicate its importance in drawing correct conclusions about potential population deficiencies and insufficiencies and in permitting the comparison of distributions between national surveys.
C1 [Sarafin, Kurtis; Brooks, Stephen P. J.] Hlth Canada, Bur Nutr Sci, Ottawa, ON K1A 0L2, Canada.
[Durazo-Arvizu, Ramon] Loyola Univ, Stritch Sch Med, Dept Publ Hlth Sci, Chicago, IL 60611 USA.
[Tian, Lu] Stanford Univ, Sch Med, Dept Hlth Res & Policy, Palo Alto, CA 94304 USA.
[Phinney, Karen W.] Natl Inst Stand & Technol, Biomol Measurement Div, Gaithersburg, MD 20899 USA.
[Tai, Susan; Camara, Johanna E.] Natl Inst Stand & Technol, Div Chem Sci, Gaithersburg, MD 20899 USA.
[Merkel, Joyce; Sempos, Christopher T.] Off Dietary Supplements, NIH, Bethesda, MD USA.
[Green, Evan] STAT Canada, Ottawa, ON, Canada.
RP Brooks, SPJ (reprint author), Hlth Canada, Bur Nutr Sci, Ottawa, ON K1A 0L2, Canada.
EM steve.brooks@hc-sc.gc.ca
FU Health Canada; NIH; National Institute of Standards and Technology;
Statistics Canada
FX Supported by Health Canada (SPJB and KS), the NIH (JM and CTS), the
National Institute of Standards and Technology (KWP, ST, and JEC), and
Statistics Canada (EG).
NR 36
TC 4
Z9 4
U1 1
U2 4
PU AMER SOC NUTRITION-ASN
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0002-9165
EI 1938-3207
J9 AM J CLIN NUTR
JI Am. J. Clin. Nutr.
PD NOV
PY 2015
VL 102
IS 5
BP 1044
EP 1050
DI 10.3945/ajcn.114.103689
PG 7
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA CV4YV
UT WOS:000364273300012
PM 26423385
ER
PT J
AU Key, TJ
Appleby, PN
Travis, RC
Albanes, D
Alberg, AJ
Barricarte, A
Black, A
Boeing, H
Bueno-de-Mesquita, HB
Chan, JM
Chen, C
Cook, MB
Donovan, JL
Galan, P
Gilbert, R
Giles, GG
Giovannucci, E
Goodman, GE
Goodman, PJ
Gunter, MJ
Hamdy, FC
Heliovaara, M
Helzlsouer, KJ
Henderson, BE
Hercberg, S
Hoffman-Bolton, J
Hoover, RN
Johansson, M
Khaw, KT
King, IB
Knekt, P
Kolonel, LN
Le Marchand, L
Mannisto, S
Martin, RM
Meyer, HE
Mondul, AM
Moy, KA
Neal, DE
Neuhouser, ML
Palli, D
Platz, EA
Pouchieu, C
Rissanen, H
Schenk, JM
Severi, G
Stampfer, MJ
Tjonneland, A
Touvier, M
Trichopoulou, A
Weinstein, SJ
Ziegler, RG
Zhou, CK
Allen, NE
AF Key, Timothy J.
Appleby, Paul N.
Travis, Ruth C.
Albanes, Demetrius
Alberg, Anthony J.
Barricarte, Aurelio
Black, Amanda
Boeing, Heiner
Bueno-de-Mesquita, H. Bas
Chan, June M.
Chen, Chu
Cook, Michael B.
Donovan, Jenny L.
Galan, Pilar
Gilbert, Rebecca
Giles, Graham G.
Giovannucci, Edward
Goodman, Gary E.
Goodman, Phyllis J.
Gunter, Marc J.
Hamdy, Freddie C.
Heliovaara, Markku
Helzlsouer, Kathy J.
Henderson, Brian E.
Hercberg, Serge
Hoffman-Bolton, Judy
Hoover, Robert N.
Johansson, Mattias
Khaw, Kay-Tee
King, Irena B.
Knekt, Paul
Kolonel, Laurence N.
Le Marchand, Loic
Mannisto, Satu
Martin, Richard M.
Meyer, Haakon E.
Mondul, Alison M.
Moy, Kristin A.
Neal, David E.
Neuhouser, Marian L.
Palli, Domenico
Platz, Elizabeth A.
Pouchieu, Camille
Rissanen, Harri
Schenk, Jeannette M.
Severi, Gianluca
Stampfer, Meir J.
Tjonneland, Anne
Touvier, Mathilde
Trichopoulou, Antonia
Weinstein, Stephanie J.
Ziegler, Regina G.
Zhou, Cindy Ke
Allen, Naomi E.
CA Endogenous Hormones Nutr
TI Carotenoids, retinol, tocopherols, and prostate cancer risk: pooled
analysis of 15 studies
SO AMERICAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Article
DE prostate cancer; carotenoids; retinol; tocopherols; vitamin E; vitamin
A; pooled analysis; nested case-control study; biomarkers
ID RANDOMIZED CONTROLLED-TRIAL; PLACEBO-CONTROLLED TRIAL; SERUM VITAMIN-A;
BETA-CAROTENE; ALPHA-TOCOPHEROL; FOLLOW-UP; PREVENTION TRIAL; SCREENING
TRIAL; DISEASE RISK; PLASMA
AB Background: Individual studies have suggested that circulating carotenoids, retinol, or tocopherols may be associated with prostate cancer risk, but the studies have not been large enough to provide precise estimates of associations, particularly by stage and grade of disease.
Objective: The objective of this study was to conduct a pooled analysis of the associations of the concentrations of 7 carotenoids, retinol, alpha-tocopherol, and gamma-tocopherol with risk of prostate cancer and to describe whether any associations differ by stage or grade of the disease or other factors.
Design: Principal investigators of prospective studies provided individual participant data for prostate cancer cases and controls. Risk by study-specific fifths of each biomarker was estimated by using multivariable-adjusted conditional logistic regression in matched case-control sets.
Results: Data were available for up to 11,239 cases (including 1654 advanced stage and 1741 aggressive) and 18,541 controls from 15 studies. Lycopene was not associated with overall risk of prostate cancer, but there was statistically significant heterogeneity by stage of disease, and the OR for aggressive disease for the highest compared with the lowest fifth of lycopene was 0.65 (95% CI: 0.46, 0.91; P-trend = 0.032). No other carotenoid was significantly associated with overall risk of prostate cancer or with risk of advanced-stage or aggressive disease. For retinol, the OR for the highest compared with the lowest fifth was 1.13 (95% CI: 1.04, 1.22; P-trend = 0.015). For alpha-tocopherol, the OR for the highest compared with the lowest fifth was 0.86 (95% CI: 0.78, 0.94; P-trend < 0.001), with significant heterogeneity by stage of disease; the OR for aggressive prostate cancer was 0.74 (95% CI: 0.59, 0.92; P-trend = 0.001). gamma-Tocopherol was not associated with risk.
Conclusions: Overall prostate cancer risk was positively associated with retinol and inversely associated with alpha-tocopherol, and risk of aggressive prostate cancer was inversely associated with lycopene and alpha-tocopherol. Whether these associations reflect causal relations is unclear.
C1 [Key, Timothy J.; Appleby, Paul N.; Travis, Ruth C.] Univ Oxford, Canc Epidemiol Unit, Nuffield Dept Populat Hlth, Oxford, England.
[Hamdy, Freddie C.] Univ Oxford, Dept Surg, Oxford, England.
[Allen, Naomi E.] Univ Oxford, Clin Trial Serv Unit, Oxford, England.
[Allen, Naomi E.] Univ Oxford, Nuffield Dept Populat Hlth, Epidemiol Studies Unit, Oxford, England.
[Albanes, Demetrius; Black, Amanda; Cook, Michael B.; Hoover, Robert N.; Mondul, Alison M.; Moy, Kristin A.; Weinstein, Stephanie J.; Ziegler, Regina G.; Zhou, Cindy Ke] US Natl Canc Inst, Div Canc Epidemiol & Genet, Bethesda, MD USA.
[Alberg, Anthony J.; Platz, Elizabeth A.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Alberg, Anthony J.] Med Univ S Carolina, Hollings Canc Ctr, Charleston, SC 29425 USA.
[Barricarte, Aurelio] Navarre Publ Hlth Inst, Pamplona, Spain.
[Barricarte, Aurelio] Consortium Biomed Res Epidemiol & Publ Hlth CIBER, Barcelona, Spain.
[Boeing, Heiner] German Inst Human Nutr Potsdam Rehbrucke, Dept Epidemiol, Nuthetal, Germany.
[Bueno-de-Mesquita, H. Bas] Natl Inst Publ Hlth & Environm, RIVM, NL-3720 BA Bilthoven, Netherlands.
[Bueno-de-Mesquita, H. Bas] Univ Med Ctr, Dept Gastroenterol & Hepatol, Utrecht, Netherlands.
[Bueno-de-Mesquita, H. Bas; Gunter, Marc J.] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, London, England.
[Chan, June M.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
[Chan, June M.] Univ Calif San Francisco, Dept Urol, San Francisco, CA 94143 USA.
[Chen, Chu] Fred Hutchinson Canc Res Ctr, Program Epidemiol, Div Publ Hlth Sci, Seattle, WA 98104 USA.
[Goodman, Phyllis J.] Fred Hutchinson Canc Res Ctr, SWOG Stat Ctr, Seattle, WA 98104 USA.
[King, Irena B.] Fred Hutchinson Canc Res Ctr, Publ Hlth Sci Core Labs, Seattle, WA 98104 USA.
[Neuhouser, Marian L.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA.
[Schenk, Jeannette M.] Fred Hutchinson Canc Res Ctr, Canc Prevent Program, Seattle, WA 98104 USA.
[Donovan, Jenny L.; Gilbert, Rebecca; Martin, Richard M.] Univ Bristol, Sch Social & Community Med, Bristol, Avon, England.
[Galan, Pilar; Hercberg, Serge; Touvier, Mathilde] Univ Paris 07, INSERM,Epidemiol & Biostatist Res Ctr, Inra,Cnam,Univ Paris 13,Univ Paris 5,U1153,U1125, Nutr Epidemiol Res Team,Sorbonne Paris Cite, Bobigny, France.
[Giles, Graham G.; Pouchieu, Camille; Severi, Gianluca] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic, Australia.
[Giovannucci, Edward; Stampfer, Meir J.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Giovannucci, Edward; Stampfer, Meir J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Giovannucci, Edward; Stampfer, Meir J.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA.
[Giovannucci, Edward; Stampfer, Meir J.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Goodman, Gary E.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Goodman, Gary E.] Univ Washington, Dept Environm Hlth, Seattle, WA 98195 USA.
[Heliovaara, Markku; Knekt, Paul; Mannisto, Satu; Rissanen, Harri] Natl Inst Hlth & Welf, Helsinki, Finland.
[Helzlsouer, Kathy J.] St Johns Mercy Med Ctr, Prevent Res Ctr, Baltimore, MD USA.
[Henderson, Brian E.] Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA.
[Hoffman-Bolton, Judy] George W Comstock Ctr Publ Hlth Res & Prevent, Hagerstown, MD USA.
[Johansson, Mattias] Int Agcy Res Canc, F-69372 Lyon, France.
[Johansson, Mattias] Umea Univ, Dept Biobank Res, Umea, Sweden.
[Khaw, Kay-Tee] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England.
[Neal, David E.] Univ Cambridge, Dept Oncol, Cambridge, England.
[Kolonel, Laurence N.; Le Marchand, Loic] Univ Hawaii, Ctr Canc, Honolulu, HI 96822 USA.
[Martin, Richard M.] Univ Bristol, MRC, Integrat Epidemiol Unit, Bristol, Avon, England.
[Martin, Richard M.] Bristol Biomed Res Unit Nutr, Natl Inst Hlth Res, Bristol, Avon, England.
[Meyer, Haakon E.] Univ Oslo, Dept Community Med, Fac Med, Oslo, Norway.
[Meyer, Haakon E.] Norwegian Inst Publ Hlth, Div Epidemiol, Oslo, Norway.
[Palli, Domenico] Canc Res & Prevent Inst ISPO, Mol & Nutr Epidemiol Unit, Florence, Italy.
[Tjonneland, Anne] Danish Canc Soc, Inst Canc Epidemiol, Copenhagen, Denmark.
[Trichopoulou, Antonia] Acad Athens, Hellen Hlth Fdn & Bur Epidemiol Res, Athens, Greece.
[King, Irena B.] Univ New Mexico, Dept Internal Med, Albuquerque, NM 87131 USA.
RP Key, TJ (reprint author), Univ Oxford, Canc Epidemiol Unit, Nuffield Dept Populat Hlth, Oxford, England.
EM titn.key@ceu.ox.ac.uk
RI Cook, Michael/A-5641-2009; Zhou, Cindy /H-2165-2015;
OI Cook, Michael/0000-0002-0533-7302; Zhou, Cindy /0000-0003-4814-4305;
Johansson, Mattias/0000-0002-3116-5081; PALLI,
Domenico/0000-0002-5558-2437; Mondul, Alison/0000-0002-8843-1416;
Mannisto, Satu/0000-0002-8668-3046; Giles, Graham/0000-0003-4946-9099
FU Cancer Research UK [C8221/A19170, C570/A11691]; Intramural Research
Program of the NIH; US Public Health Service from the National Cancer
Institute, Department of Health and Human Services [N01-CN-45165,
N01-RC-45035, N01-RC-37004, HHSN261201000006C]; NIH, Department of
Health and Human Services [U01 CA63673, R01 CA96789, N01 PC35142];
National Cancer Institute, NIH [CA 94028]; Hellenic Health Foundation;
Dutch Ministry of Public Health, Welfare and Sports (VWS); Netherlands
Cancer Registry (NKR); LK Research Funds; Dutch Prevention Funds; Dutch
Zorg Onderzoek Nederland; World Cancer Research Fund; Statistics
Netherlands; National Cancer Institute [CA 55075, CA 72036, P01 CA
33619, R37 CA 54281, 1-UM1-CA164973]; NIH [CA37429, P01 CA108964];
Norwegian Cancer Society; Throne Hoist Foundation; VicHealth; Cancer
Council Victoria; Australian National Health and Medical Research
Council [209057, 251553, 504711]; United Kingdom National Institute for
Health Research Health Technology Assessment Programme [96/20/06,
96/20/99]; Medical Research Council; University of Bristol; National
Institute for Health Research
FX Supported by Cancer Research UK grants C8221/A19170 and C570/A11691,
Funding for the collaborating studies was as follows. Alpha-Tocopherol,
Beta-Carotene Cancer Prevention Study: Supported in part by the
Intramural Research Program of the NIH and the National Cancer
Institute; also, this research was supported by US Public Health Service
contracts N01-CN-45165, N01-RC-45035, N01-RC-37004, and
HHSN261201000006C from the National Cancer Institute, Department of
Health and Human Services. beta-Carotene and Retinol Efficacy Trial:
Supported by U01 CA63673, R01 CA96789, and N01 PC35142, all from the
NIH, Department of Health and Human Services. CLUE I and II: Supported
by CA 94028 from the National Cancer Institute, NIH. European
Prospective Investigation into Cancer and Nutrition Greece: Supported by
the Hellenic Health Foundation. European Prospective Investigation into
Cancer and Nutrition Netherlands: Supported by the Dutch Ministry of
Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry
(NKR), LK Research Funds, Dutch Prevention Funds, Dutch Zorg Onderzoek
Nederland, World Cancer Research Fund, Statistics Netherlands. Health
Professionals Follow-Up Study: Supported by CA 55075 and CA 72036 from
the National Cancer Institute and the NIH. Janus: The serum analysis of
vitamins was supported by a grant from the Norwegian Cancer Society and
the Throne Hoist Foundation. Melbourne Collaborative Cohort Study
(MCCS): Cohort recruitment was funded by VicHealth and Cancer Council
Victoria. The MCCS was further supported by Australian National Health
and Medical Research Council grants 209057, 251553, and 504711 and by
infrastructure provided by Cancer Council Victoria. Multiethnic Cohort:
Supported by National Cancer Institute grants P01 CA 33619, R37 CA
54281, and 1-UM1-CA164973. Prostate Cancer Prevention Trial: Supported
by National Cancer Institute and NIH, CA37429 and P01 CA108964. Prostate
testing for cancer and Treatment trial: Funded by the United Kingdom
National Institute for Health Research Health Technology Assessment
Programme (projects 96/20/06, 96/20/99, www.hta/1230); the views and
opinions expressed therein are those of the authors and do not
necessarily reflect those of the Department of Health. The University of
Bristol Integrated Epidemiology Unit is supported by the Medical
Research Council and the University of Bristol. The Bristol Nutrition
Biomedical Research Unit is funded by the National Institute for Health
Research and is a partnership between the University Hospitals Bristol
National Health Service Foundation Trust and the University of Bristol.
SU.VI.MAX, SUpplementation en VItamines et Mineraux Anti-oXydants trial:
Supported by the Direction Generale de la Sante (French Ministry of
Health) for laboratory assays.
NR 53
TC 11
Z9 11
U1 1
U2 15
PU AMER SOC NUTRITION-ASN
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0002-9165
EI 1938-3207
J9 AM J CLIN NUTR
JI Am. J. Clin. Nutr.
PD NOV
PY 2015
VL 102
IS 5
BP 1142
EP 1157
DI 10.3945/ajcn.115.114306
PG 16
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA CV4YV
UT WOS:000364273300023
PM 26447150
ER
PT J
AU Fretts, AM
Follis, JL
Nettleton, JA
Lemaitre, RN
Ngwa, JS
Wojczynski, MK
Kalafati, IP
Varga, TV
Frazier-Wood, AC
Houston, DK
Lahti, J
Ericson, U
van den Hooven, EH
Mikkila, V
Kiefte-de Jong, JC
Mozaffarian, D
Rice, K
Renstrom, F
North, KE
McKeown, NM
Feitosa, MF
Kanoni, S
Smith, CE
Garcia, ME
Tiainen, AM
Sonestedt, E
Manichaikul, A
Van Rooij, FJA
Dimitriou, M
Raitakari, O
Pankow, JS
Djousse, L
Province, MA
Hu, FB
Lai, CQ
Keller, MF
Perala, MM
Rotter, JI
Hofman, A
Graff, M
Kahonen, M
Mukamal, K
Johansson, I
Ordovas, JM
Liu, YM
Mannisto, S
Uitterlinden, AG
Deloukas, P
Seppala, I
Psaty, BM
Cupples, LA
Borecki, IB
Franks, PW
Arnett, DK
Nalls, MA
Eriksson, JG
Orho-Melander, M
Franco, OH
Lehtimaki, T
Dedoussis, GV
Meigs, JB
Siscovick, DS
AF Fretts, Amanda M.
Follis, Jack L.
Nettleton, Jennifer A.
Lemaitre, Rozenn N.
Ngwa, Julius S.
Wojczynski, Mary K.
Kalafati, Ioanna Panagiota
Varga, Tibor V.
Frazier-Wood, Alexis C.
Houston, Denise K.
Lahti, Jari
Ericson, Ulrika
van den Hooven, Edith H.
Mikkilae, Vera
Kiefte-de Jong, Jessica C.
Mozaffarian, Dariush
Rice, Kenneth
Renstroem, Frida
North, Kari E.
McKeown, Nicola M.
Feitosa, Mary F.
Kanoni, Stavroula
Smith, Caren E.
Garcia, Melissa E.
Tiainen, Anna-Maija
Sonestedt, Emily
Manichaikul, Ani
van Rooij, Frank J. A.
Dimitriou, Maria
Raitakari, Olli
Pankow, James S.
Djousse, Luc
Province, Michael A.
Hu, Frank B.
Lai, Chao-Qiang
Keller, Margaux F.
Peraelae, Mia-Maria
Rotter, Jerome I.
Hofman, Albert
Graff, Misa
Kaehoenen, Mika
Mukamal, Kenneth
Johansson, Ingegerd
Ordovas, Jose M.
Liu, Yongmei
Maennistoe, Satu
Uitterlinden, Andre G.
Deloukas, Panos
Seppaelae, Ilkka
Psaty, Bruce M.
Cupples, L. Adrienne
Borecki, Ingrid B.
Franks, Paul W.
Arnett, Donna K.
Nalls, Mike A.
Eriksson, Johan G.
Orho-Melander, Marju
Franco, Oscar H.
Lehtimaeki, Terho
Dedoussis, George V.
Meigs, James B.
Siscovick, David S.
TI Consumption of meat is associated with higher fasting glucose and
insulin concentrations regardless of glucose and insulin genetic risk
scores: a meta-analysis of 50,345 Caucasians
SO AMERICAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Article
DE gene-diet interaction; glucose; insulin; meat intake; diet;
meta-analysis
ID GENOME-WIDE ASSOCIATION; CORONARY-HEART-DISEASE; C-REACTIVE PROTEIN;
DIABETES-MELLITUS; SUSCEPTIBILITY LOCI; CHARGE CONSORTIUM; UNPROCESSED
RED; OLDER-ADULTS; TYPE-2; WOMEN
AB Background: Recent studies suggest that meat intake is associated with diabetes-related phenotypes. However, whether the associations of meat intake and glucose and insulin homeostasis are modified by genes related to glucose and insulin is unknown.
Objective: We investigated the associations of meat intake and the interaction of meat with genotype on fasting glucose and insulin concentrations in Caucasians free of diabetes mellitus.
Design: Fourteen studies that are part of the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium participated in the analysis. Data were provided for up to 50,345 participants. Using linear regression within studies and a fixed-effects meta-analysis across studies, we examined l) the associations of processed meat and unprocessed red meat intake with fasting glucose and insulin concentrations; and 2) the interactions of processed meat and unprocessed red meat with genetic risk score related to fasting glucose or insulin resistance on fasting glucose and insulin concentrations.
Results: Processed meat was associated with higher fasting glucose, and unprocessed red meat was associated with both higher fasting glucose and fasting insulin concentrations after adjustment for potential confounders [not including body mass index (BMI)]. For every additional 50-g serving of processed meat per day, fasting glucose was 0.021 mmol/L (95% CI: 0.011, 0.030 mmol/L) higher. Every additional 100-g serving of unprocessed red meat per day was associated with a 0.037-mmol/L (95% CI: 0.023, 0.051-mmol/L) higher fasting glucose concentration and a 0.049-1n-pmon (95% CI: 0.035, 0.063-1n-pmol/L) higher fasting insulin concentration. After additional adjustment for BMI, observed associations were attenuated and no longer statistically significant. The association of processed meat and fasting insulin did not reach statistical significance after correction for multiple comparisons. Observed associations were not modified by genetic loci known to influence fasting glucose or insulin resistance.
Conclusion: The association of higher fasting glucose and insulin concentrations with meat consumption was not modified by an index of glucose- and insulin-related single-nucleotide polymorphisms.
C1 [Fretts, Amanda M.; Psaty, Bruce M.; Siscovick, David S.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Lemaitre, Rozenn N.; Psaty, Bruce M.; Siscovick, David S.] Univ Washington, Dept Med, Seattle, WA 98195 USA.
[Rice, Kenneth] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA.
[Fretts, Amanda M.; Lemaitre, Rozenn N.; Siscovick, David S.] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.
[Frazier-Wood, Alexis C.] Baylor Coll Med, Dept Pediat, Childrens Nutr Res Ctr, USDA ARS, Houston, TX 77030 USA.
[Nettleton, Jennifer A.] Univ Texas Hlth Sci Ctr Houston, Div Epidemiol Human Genet & Environm Sci, Houston, TX USA.
[Follis, Jack L.] Univ St Thomas, Dept Math Comp Sci & Cooperat Engn, Houston, TX 77006 USA.
[Ngwa, Julius S.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA.
[Wojczynski, Mary K.; Feitosa, Mary F.; Province, Michael A.; Borecki, Ingrid B.] Washington Univ, Sch Med, Div Stat Gen, Dept Genet, St Louis, MO USA.
[Kalafati, Ioanna Panagiota; Dimitriou, Maria; Dedoussis, George V.] Harokopio Univ Athens, Dept Nutr & Dietet, Athens, Greece.
[Varga, Tibor V.; Renstroem, Frida; Franks, Paul W.] Lund Univ, Dept Clin Sci, Genet & Mol Epidemiol Unit, Malmo, Sweden.
[Ericson, Ulrika; Sonestedt, Emily; Orho-Melander, Marju] Lund Univ, Dept Clin Sci, Malmo, Sweden.
[Renstroem, Frida] Umea Univ, Dept Biobank Res, Umea, Sweden.
[Johansson, Ingegerd] Umea Univ, Dept Odontol, Umea, Sweden.
[Franks, Paul W.] Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden.
[Houston, Denise K.] Wake Forest Univ, Bowman Gray Sch Med, Dept Internal Med, Winston Salem, NC 27103 USA.
[Liu, Yongmei] Wake Forest Univ, Bowman Gray Sch Med, Dept Epidemiol & Prevent, Div Publ Hlth Sci, Winston Salem, NC 27103 USA.
[Lahti, Jari] Univ Helsinki, Inst Behav Sci, Helsinki, Finland.
[Mikkilae, Vera] Univ Helsinki, Dept Food & Environm Sci, Helsinki, Finland.
[Eriksson, Johan G.] Univ Helsinki, Dept Gen Practice & Primary Hlth Care, Helsinki, Finland.
[van den Hooven, Edith H.; Kiefte-de Jong, Jessica C.; van Rooij, Frank J. A.; Hofman, Albert; Uitterlinden, Andre G.; Franco, Oscar H.] Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands.
[Uitterlinden, Andre G.] Erasmus Univ, Med Ctr, Dept Internal Med, Rotterdam, Netherlands.
[Mikkilae, Vera; Raitakari, Olli] Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, Turku, Finland.
[Hu, Frank B.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Hu, Frank B.; Franks, Paul W.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Djousse, Luc] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
[Mozaffarian, Dariush] Tufts Univ, Friedman Sch Nutr Sci & Policy, Boston, MA 02111 USA.
[North, Kari E.; Graff, Misa] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA.
[North, Kari E.] Univ N Carolina, Carolina Ctr Genome Sci, Chapel Hill, NC USA.
[McKeown, Nicola M.] Tufts Univ, Nutr Epidemiol Program, Boston, MA 02111 USA.
[McKeown, Nicola M.; Lai, Chao-Qiang; Ordovas, Jose M.] Tufts Univ, Jean Mayer USDA, Human Nutr Res Ctr Aging, Boston, MA 02111 USA.
[Smith, Caren E.; Lai, Chao-Qiang; Ordovas, Jose M.] Tufts Univ, Nutr & Genom Lab, Boston, MA 02111 USA.
[Kanoni, Stavroula; Deloukas, Panos] Barts, William Harvey Res Inst, London, England.
[Kanoni, Stavroula] Queen Mary Univ London, London Sch Med & Dent, London, England.
[Garcia, Melissa E.] NIA, Lab Epidemiol & Populat Sci, Bethesda, MD 20892 USA.
[Keller, Margaux F.] NIA, Neurogenet Lab, Bethesda, MD 20892 USA.
[Tiainen, Anna-Maija; Peraelae, Mia-Maria; Maennistoe, Satu] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland.
[Manichaikul, Ani] Univ Virginia, Ctr Publ Hlth Genom, Dept Publ Hlth Sci, Div Biostat & Epidemiol, Charlottesville, VA USA.
[van Rooij, Frank J. A.] Netherlands Genom Initiat, Leiden, Netherlands.
[Raitakari, Olli] Turku Univ Hosp, Dept Clin Physiol & Nucl Med, FIN-20520 Turku, Finland.
[Pankow, James S.] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA.
[Rotter, Jerome I.] Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Inst Translat Genom & Populat Sci, Torrance, CA 90509 USA.
[Keller, Margaux F.] Univ Tampere, Dept Clin Physiol, FIN-33101 Tampere, Finland.
[Seppaelae, Ilkka; Lehtimaeki, Terho] Univ Tampere, Dept Clin Chem, FIN-33101 Tampere, Finland.
[Seppaelae, Ilkka; Lehtimaeki, Terho] Univ Tampere, Fimlab Labs, FIN-33101 Tampere, Finland.
[Kaehoenen, Mika; Seppaelae, Ilkka; Lehtimaeki, Terho] Univ Tampere, Sch Med, FIN-33101 Tampere, Finland.
[Kaehoenen, Mika] Univ Tampere, Tampere Univ Hosp, FIN-33101 Tampere, Finland.
[Mukamal, Kenneth] Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, Boston, MA 02215 USA.
[Ordovas, Jose M.] Cardiovasc Res Ctr, Dept Epidemiol & Populat Genet, Madrid, Spain.
[Ordovas, Jose M.] IMDEA Food Inst, Madrid, Spain.
[Deloukas, Panos] King Abdulaziz Univ, Princess Al Jawhara Al Brahim Ctr Excellence Res, Jeddah 21413, Saudi Arabia.
[Cupples, L. Adrienne] Framingham Heart Dis Epidemiol Study, Framingham, MA USA.
[Arnett, Donna K.] Univ Alabama Birmingham, Sch Publ Hlth, Dept Epidemiol, Birmingham, AL 35294 USA.
[Eriksson, Johan G.] Univ Helsinki, Cent Hosp, Gen Practice Unit, Helsinki, Finland.
[Eriksson, Johan G.] Folkhalsan Res Ctr, Helsinki, Finland.
[Meigs, James B.] Massachusetts Gen Hosp, Div Gen Med, Clin Epidemiol Unit, Boston, MA 02114 USA.
[Meigs, James B.] Massachusetts Gen Hosp, Div Gen Med, Diabet Res Unit, Boston, MA 02114 USA.
[Psaty, Bruce M.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA.
[Siscovick, David S.] New York Acad Med, New York, NY USA.
RP Fretts, AM (reprint author), Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
EM amfretts@uw.edu
RI Sonestedt, Emily/I-3814-2016; Deloukas, Panos/B-2922-2013; Feitosa,
Mary/K-8044-2012; Djousse, Luc/F-5033-2017;
OI Sonestedt, Emily/0000-0002-0747-4562; Deloukas,
Panos/0000-0001-9251-070X; Feitosa, Mary/0000-0002-0933-2410; Djousse,
Luc/0000-0002-9902-3047; Mannisto, Satu/0000-0002-8668-3046; Kiefte-de
Jong, Jessica/0000-0002-8136-0918; Lahti, Jari/0000-0002-4310-5297
FU National Heart, Lung, and Blood Institute (NHLBI) [R01HL105756];
Institute of Translational Health Sciences [5KL2TR000421-08]; NHLBI
[T32HL007902]
FX Infrastructure for the Cohorts for Heart and Aging Research in Genomic
Epidemiology Consortium is supported in part by National Heart, Lung,
and Blood Institute (NHLBI) grant R01HL105756. This meta-analysis was
supported by the Institute of Translational Health Sciences
(5KL2TR000421-08) and NHLBI (T32HL007902). Sources of support for the
participating cohorts are provided in Supplemental Table 12. Funders had
no role in the design, implementation, analysis, and interpretation of
the data for the studies.
NR 65
TC 6
Z9 6
U1 4
U2 23
PU AMER SOC NUTRITION-ASN
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0002-9165
EI 1938-3207
J9 AM J CLIN NUTR
JI Am. J. Clin. Nutr.
PD NOV
PY 2015
VL 102
IS 5
BP 1266
EP 1278
DI 10.3945/ajcn.114.101238
PG 13
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA CV4YV
UT WOS:000364273300036
PM 26354543
ER
PT J
AU Klauzinska, M
McCurdy, D
Rangel, MC
Vaidyanath, A
Castro, NP
Shen, MM
Gonzales, M
Bertolette, D
Bianco, C
Callahan, R
Salomon, DS
Raafat, A
AF Klauzinska, Malgorzata
McCurdy, David
Rangel, Maria Cristina
Vaidyanath, Arun
Castro, Nadia P.
Shen, Michael M.
Gonzales, Monica
Bertolette, Daniel
Bianco, Caterina
Callahan, Robert
Salomon, David S.
Raafat, Ahmed
TI Cripto-1 Ablation Disrupts Alveolar Development in the Mouse Mammary
Gland through a Progesterone Receptor-Mediated Pathway
SO AMERICAN JOURNAL OF PATHOLOGY
LA English
DT Article
ID EPITHELIAL-MESENCHYMAL TRANSITION; PLURIPOTENT STEM-CELLS; TRANSGENIC
MICE; BRANCHING MORPHOGENESIS; RETINOIC ACID; KNOCKOUT MICE; KEY STAGES;
LINE T-47D; KAPPA-B; EXPRESSION
AB Cripto-1, a member of the epidermal growth factor-Cripto-1/FRL-1/Cryptic family, is critical for early embryonic development. Together with its ligand Nodal, Cripto-1 has been found to be associated with the undifferentiated status of mouse and human embryonic stem cells. Several studies have clearly shown that Cripto-1 is involved in regulating branching morphogenesis and epithelialmesenchymal transition of the mammary gland both in vitro and in vivo and together with the cofactor GRP78 is critical for the maintenance of mammary stem cells ex vivo. Our previous studies showed that mammary-specific overexpression of human Cripto-1 exhibited dramatic morphological alterations in nulliparous mice mammary glands. The present study shows a novel mechanism for Cripto-1 regulation of mammary gland development through direct effects on progesterone receptor expression and pathways regulated by progesterone in the mammary gland. We demonstrate a strict temporal regulation of mouse Cripto-1 (mCripto-1) expression that occurs during mammary gland development and a stage-specific function of mCripto-1 signaling during mammary gland development. Our data suggest that Cripto-1, like the progesterone receptor, is not required for the initial ductal growth but is essential for subsequent side branching and alveologenesis during the initial stages of pregnancy. Dissection of the mechanism by which this occurs indicates that mCripto-1 activates receptor activator NF-kappa B/receptor activator NF-kappa B ligand, and NF-kappa B signaling pathways.
C1 [Klauzinska, Malgorzata; Rangel, Maria Cristina; Castro, Nadia P.; Gonzales, Monica; Bertolette, Daniel; Bianco, Caterina; Salomon, David S.] NCI, Mouse Canc Genet Program, Frederick, MD 21701 USA.
[McCurdy, David; Vaidyanath, Arun; Callahan, Robert; Raafat, Ahmed] NCI, Basic Res Lab, NIH, Bethesda, MD 20892 USA.
[Shen, Michael M.] Columbia Univ, Med Ctr, Dept Med Genet & Dev, New York, NY USA.
[Shen, Michael M.] Columbia Univ, Med Ctr, Dept Urol, New York, NY USA.
[Shen, Michael M.] Columbia Univ, Med Ctr, Dept Syst Biol, New York, NY USA.
RP Raafat, A (reprint author), NCI, Basic Res Lab, NIH, 37 Convent Dr,Bldg 37,Room 1118, Bethesda, MD 20892 USA.
EM raafata@mail.nih.gov
RI Shen, Michael/C-7546-2009
OI Shen, Michael/0000-0002-4042-1657
FU Intramural Research Program of the NIH, National Cancer Institute
(Bethesda, MD)
FX Supported by Intramural Research Program of the NIH, National Cancer
Institute (Bethesda, MD).
NR 78
TC 3
Z9 3
U1 0
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9440
EI 1525-2191
J9 AM J PATHOL
JI Am. J. Pathol.
PD NOV
PY 2015
VL 185
IS 11
BP 2907
EP 2922
DI 10.1016/j.ajpath.2015.07.023
PG 16
WC Pathology
SC Pathology
GA CV7FY
UT WOS:000364439000006
PM 26429739
ER
PT J
AU Jain, S
Chen, J
Nicolae, A
Wang, HS
Shin, DM
Adkins, EB
Sproule, TJ
Leeth, CM
Sakai, T
Kovalchuk, AL
Raffeld, M
Ward, JM
Rehg, JE
Waldmann, TA
Jaffe, ES
Roopenian, DC
Morse, HC
AF Jain, Shweta
Chen, Jing
Nicolae, Alina
Wang, Hongsheng
Shin, Dong-Mi
Adkins, Elisabeth B.
Sproule, Thomas J.
Leeth, Caroline M.
Sakai, Tomomi
Kovalchuk, Alexander L.
Raffeld, Mark
Ward, Jerrold M.
Rehg, Jerold E.
Waldmann, Thomas A.
Jaffe, Elaine S.
Roopenian, Derry C.
Morse, Herbert C., III
TI IL-21-Driven Neoplasms in SJL Mice Mimic Some Key Features of Human
Angioimmunoblastic T-Cell Lymphoma
SO AMERICAN JOURNAL OF PATHOLOGY
LA English
DT Article
ID FOLLICULAR-HELPER-CELLS; REVERSE IMMUNE SURVEILLANCE; MURINE LEUKEMIA
VIRUSES; GERMINAL CENTER; B-CELLS; GROWTH; SUPERANTIGEN; AUTOIMMUNITY;
EXPRESSION; EXPANSION
AB SJL/J mice exhibit a high incidence of mature B-cell lymphomas that require CD4(+) T cells for their development. We found that their spleens and lymph nodes contained increased numbers of germinal centers and T follicular helper (T-FH) cells. Microarray analyses revealed high levels of transcripts encoding IL-21 associated with high levels of serum IL-21. We developed IL-21 receptor (IL21R)-deficient Swiss Jim Lambart (SJL) mice to determine the role of IL-21 in disease. These mice had reduced numbers of T-FH cells, lower serum Levels of IL-21, and few germinal center B cells, and they did not develop B-cell tumors, suggesting IL-21-dependent B-cell lymphomagenesis. We also noted a series of features common to SJL disease and human angioimmunoblastic T-cell lymphoma (AITL), a malignancy of T-FH cells. Gene expression analyses of AITL showed that essentially all cases expressed elevated Levels of transcripts for IL21, IL21R, and a series of genes associated with T-FH cell development and function. These results identify a mouse model with features of AITL and suggest that patients with the disease might benefit from therapeutic interventions that interrupt IL-21 signaling.
C1 [Jain, Shweta; Wang, Hongsheng; Shin, Dong-Mi; Sakai, Tomomi; Kovalchuk, Alexander L.; Ward, Jerrold M.; Morse, Herbert C., III] NIAID, Virol & Cellular Immunol Sect, Immunogenet Lab, Rockville, MD 20852 USA.
[Chen, Jing; Waldmann, Thomas A.] NCI, Lymphoid Malignancies Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Nicolae, Alina; Raffeld, Mark; Jaffe, Elaine S.] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Shin, Dong-Mi] Seoul Natl Univ, Dept Food & Nutr, Seoul, South Korea.
[Adkins, Elisabeth B.; Sproule, Thomas J.; Roopenian, Derry C.] Jackson Lab, Bar Harbor, ME 04609 USA.
[Adkins, Elisabeth B.; Leeth, Caroline M.; Roopenian, Derry C.] Tufts Univ, Sackler Sch Grad Biomed Sci, Genet Program, Boston, MA 02111 USA.
[Leeth, Caroline M.] Virginia Polytech Inst & State Univ, Coll Agr & Life Sci, Dept Anim & Poultry Sci, Blacksburg, VA 24061 USA.
[Rehg, Jerold E.] St Jude Childrens Res Hosp, Dept Pathol, Memphis, TN 38105 USA.
RP Morse, HC (reprint author), NIAID, Virol & Cellular Immunol Sect, NIH, Room 1421,Twinbrook Bldg 1,MSC 8152, Rockville, MD 20852 USA.
EM hmorse@niaid.nih.gov
FU Intramural Research Program of the NIH; National Institute of Allergy
and Infectious Diseases; National Cancer Institute; Alliance for Lupus
Research; Lakeside Foundation; Seoul National University; NIH; Jackson
Laboratory's Education Program
FX Supported, in part, by the Intramural Research Program of the NIH, the
National Institute of Allergy and Infectious Diseases (H.C.M., H.W.,
A.L.K., S.J., T.S., D.-M.S., and J.M.W.), and the National Cancer
Institute (J.C., E.S.J., AN., and T.A.W.), in part by the Alliance for
Lupus Research (D.C.R.) and the Lakeside Foundation (D.C.R.), and in
part by Seoul National University (D.-M.S.). C.M.L. was supported in
part by an NIH training grant. E.B.A. was supported by The Jackson
Laboratory's Education Program.
NR 50
TC 3
Z9 3
U1 2
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9440
EI 1525-2191
J9 AM J PATHOL
JI Am. J. Pathol.
PD NOV
PY 2015
VL 185
IS 11
BP 3102
EP 3114
DI 10.1016/j.ajpath.2015.07.021
PG 13
WC Pathology
SC Pathology
GA CV7FY
UT WOS:000364439000021
PM 26363366
ER
PT J
AU Miller, AH
Vayttaden, SJ
Al-Khodor, S
Fraser, IDC
AF Miller, Alexandra H.
Vayttaden, Sharat J.
Al-Khodor, Souhaila
Fraser, Iain D. C.
TI Assay Development for Image-Based Quantification of Intracellular
Bacterial Replication and Analysis of the Innate Immune Response to
Infection
SO ASSAY AND DRUG DEVELOPMENT TECHNOLOGIES
LA English
DT Article; Proceedings Paper
CT 2nd Annual Conference of the
Society-for-Biomolecular-Imaging-and-Informatics
CY SEP 15-17, 2015
CL Harvard Med Sch, Boston, MA
SP Soc Biomolecular Imaging & Informat
HO Harvard Med Sch
ID BURKHOLDERIA-CEPACIA COMPLEX; CYSTIC-FIBROSIS; AUTOPHAGY; MACROPHAGES;
MECHANISMS; MITOPHAGY
AB Severe bacterial infection can lead to inflammation, host tissue damage, and ultimately disseminated septic shock. The mammalian innate immune system responds to microbial infection through the detection of invariant pathogen-associated molecular patterns (PAMPs) by a range of pattern recognition receptors (PRRs) expressed by the host cell. A successful immune response involves tightly coordinated signaling from these receptors, leading to a robust transcriptional response producing cytokines and antimicrobial effectors. While the PRR-expressing phagocytes of the host innate immune system function to contain and degrade internalized bacteria through pathways such as selective autophagy, pathogenic bacteria may subvert this process to replicate in the host cell. We describe the development of imaging assays to investigate these host-pathogen interactions through gene perturbation screens, which could lead to the identification of novel effectors of the host response to bacterial infection. We identify markers of coordinated initial signaling in macrophages challenged with ligands to PRRs of the toll-like receptor (TLR) family and compare this response to that induced by intact bacteria of the Burkholderia cenocepacia complex (Bcc), an opportunistic pathogen that causes life-threatening infections in patients with cystic fibrosis and chronic granulomatous disease. Bcc has been shown to escape the endocytic pathway, activate selective autophagy, and replicate within human macrophages. We demonstrate robust image-based quantification of multiple stages of Bcc infection of macrophages: ubiquitin tagging of cytosolic bacteria, recruitment of selective autophagy effector proteins, and intracellular bacterial replication, and we show perturbation of bacterial replication using drug treatment or siRNA-based gene knockdown. The described panel of imaging assays can be extended to other bacterial infections and pathogenic ligand combinations where high-content siRNA screening could provide significant new insight into regulation of the innate immune response to infection.
C1 [Miller, Alexandra H.; Vayttaden, Sharat J.; Fraser, Iain D. C.] NIAID, Signaling Syst Unit, Lab Syst Biol, NIH, Bethesda, MD 20892 USA.
[Al-Khodor, Souhaila] Sidra Med & Res Ctr, Div Translat Med, Infect Dis Unit, Doha, Qatar.
RP Fraser, IDC (reprint author), NIAID, Signaling Syst Unit, Lab Syst Biol, NIH, 9000 Rockville Pike,Bldg 4,Rm 109A,MSC 0421, Bethesda, MD 20892 USA.
EM fraseri@niaid.nih.gov
OI Al Khodor, Souhaila/0000-0003-4858-7130
FU Intramural Research Program of the National Institute of Allergy and
Infectious Diseases
FX This work was generously supported by the Intramural Research Program of
the National Institute of Allergy and Infectious Diseases (A.H.M.,
S.J.V., and I.D.C.F).
NR 22
TC 0
Z9 0
U1 0
U2 1
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1540-658X
EI 1557-8127
J9 ASSAY DRUG DEV TECHN
JI ASSAY DRUG DEV. TECHNOL.
PD NOV 1
PY 2015
VL 13
IS 9
SI SI
BP 515
EP 528
DI 10.1089/adt.2015.664
PG 14
WC Biochemical Research Methods; Pharmacology & Pharmacy
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy
GA CW2NZ
UT WOS:000364830500003
PM 26505731
ER
PT J
AU Ann, J
Jung, A
Kim, MY
Kim, HM
Ryu, H
Kim, S
Kang, DW
Hong, S
Cui, M
Choi, S
Blumberg, PM
Frank-Foltyn, R
Bahrenberg, G
Stockhausen, H
Christoph, T
Lee, J
AF Ann, Jihyae
Jung, Aeran
Kim, Mi-Yeon
Kim, Hyuk-Min
Ryu, HyungChul
Kim, Sunjoo
Kang, Dong Wook
Hong, Sunhye
Cui, Minghua
Choi, Sun
Blumberg, Peter M.
Frank-Foltyn, Robert
Bahrenberg, Gregor
Stockhausen, Hannelore
Christoph, Thomas
Lee, Jeewoo
TI Structure activity relationships of benzyl C-region analogs of
2-(3-fluoro-4-methylsulfonamidophenyl)propanamides as potent TRPV1
antagonists
SO BIOORGANIC & MEDICINAL CHEMISTRY
LA English
DT Article
DE Vanilloid receptor 1; TRPV1 antagonists; Analgesic
ID VANILLOID CAPSAICIN RECEPTORS; ANALGESIC AGENTS; AGONIST ACTIVITY;
2-(3-FLUORO-4-METHYLSULFONYLAMINOPHENYL)PROPANAMIDES
AB A series of 2-substituted 4-(trifluoromethyl)benzyl C-region analogs of 2-(3-fluoro-4-methylsulfonamidophenyl)propanamides were investigated for hTRPV1 antagonism. The analysis indicated that the phenyl C-region derivatives exhibited better antagonism than those of the corresponding pyridine surrogates for most of the series examined. Among the phenyl C-region derivatives, the two best compounds 43 and 445 antagonized capsaicin selectively relative to their antagonism of other activators and showed excellent potencies with K-i(CAP) = 0.3 nM. These two compounds blocked capsaicin-induced hypothermia, consistent with TRPV1 as their site of action, and they demonstrated promising analgesic activities in a neuropathic pain model without hyperthermia. The docking study of 445 in our hTRPV1 homology model indicated that its binding mode was similar with that of its pyridine surrogate in the A- and B-regions but displayed a flipped configuration in the C-region. (C) 2015 Elsevier Ltd. All rights reserved.
C1 [Ann, Jihyae; Jung, Aeran; Kim, Mi-Yeon; Kim, Hyuk-Min; Lee, Jeewoo] Seoul Natl Univ, Pharmaceut Sci Res Inst, Coll Pharm, Med Chem Lab, Seoul 151742, South Korea.
[Ryu, HyungChul; Kim, Sunjoo] J2H Biotech, Ansan, Gyeonggi Do, South Korea.
[Kang, Dong Wook] Catholic Univ Deagu, Dept Pharmaceut Sci & Technol, Coll Hlth & Med Sci, Gyongsan 712702, Gyeongsangbuk D, South Korea.
[Hong, Sunhye; Cui, Minghua; Choi, Sun] Ewha Womans Univ, Grad Sch Pharmaceut Sci, Coll Pharm, Natl Leading Res Lab Mol Modeling & Drug Design, Seoul 120750, South Korea.
[Hong, Sunhye; Cui, Minghua; Choi, Sun] Ewha Womans Univ, Global Top Res Program 5, Seoul 120750, South Korea.
[Blumberg, Peter M.] NCI, Lab Canc Biol & Genet, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Frank-Foltyn, Robert; Bahrenberg, Gregor; Stockhausen, Hannelore; Christoph, Thomas] Grunenthal GmbH, Grunenthal Innovat, D-52078 Aachen, Germany.
RP Lee, J (reprint author), Seoul Natl Univ, Pharmaceut Sci Res Inst, Coll Pharm, Med Chem Lab, Seoul 151742, South Korea.
EM jeewoo@snu.ac.kr
FU Grunenthal in Germany; Korea Science and Engineering Foundation (KOSEF)
[NRF-2007-0057057]; National Leading Research Lab (NLRL) program in
South Korea [2011-0028885]; NIH, Center for Cancer Research, NCI in the
USA [Z1A BC 005270]
FX This research was supported by research Grants from Grunenthal in
Germany, grants from the Korea Science and Engineering Foundation
(KOSEF) (NRF-2007-0057057) and the National Leading Research Lab (NLRL)
program (2011-0028885) in South Korea, and in part by the Intramural
Research Program of the NIH, Center for Cancer Research, NCI (Project
Z1A BC 005270) in the USA.
NR 25
TC 2
Z9 2
U1 2
U2 3
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0968-0896
EI 1464-3391
J9 BIOORGAN MED CHEM
JI Bioorg. Med. Chem.
PD NOV 1
PY 2015
VL 23
IS 21
BP 6844
EP 6854
DI 10.1016/j.bmc.2015.10.001
PG 11
WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry,
Organic
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry
GA CV7FI
UT WOS:000364437400007
PM 26474664
ER
PT J
AU Stone, EL
Citossi, F
Singh, R
Kaur, B
Gaskell, M
Farmer, PB
Monks, A
Hose, C
Stevens, MFG
Leong, CO
Stocks, M
Kellam, B
Marlow, M
Bradshaw, TD
AF Stone, Erica L.
Citossi, Francesca
Singh, Rajinder
Kaur, Balvinder
Gaskell, Margaret
Farmer, Peter B.
Monks, Anne
Hose, Curtis
Stevens, Malcolm F. G.
Leong, Chee-Onn
Stocks, Michael
Kellam, Barrie
Marlow, Maria
Bradshaw, Tracey D.
TI Antitumour benzothiazoles. Part 32: DNA adducts and double strand breaks
correlate with activity; synthesis of 5F203 hydrogels for local delivery
SO BIOORGANIC & MEDICINAL CHEMISTRY
LA English
DT Article
DE Antitumour benzothiazoles; GW 610; 5F 203; DNA adducts; DNA double
strand breaks; Low molecular weight gelators (LMWGs)
ID MOLECULAR-WEIGHT HYDROGELS; CYTOCHROME P450S 1A1; AMINO-ACID PRODRUGS;
CANCER CELL-LINES; IN-VITRO; DRUG-DELIVERY; COLORECTAL-CANCER;
BIOLOGICAL-PROPERTIES; TUMOR-CELLS; NSC 721648
AB Potent, selective antitumour AhR ligands 5F 203 and GW 610 are bioactivated by CYPs 1A1 and 2W1. Herein we reason that DNA adducts' generation resulting in lethal DNA double strand breaks (DSBs) underlies benzothiazoles' activity. Treatment of sensitive carcinoma cell lines with GW 610 generated co-eluting DNA adducts (R-2 > 0.7). Time-dependent appearance of gamma-H2AX foci revealed subsequent DNA double strand breaks. Propensity for systemic toxicity of benzothiazoles steered development of prodrugs' hydrogels for localised delivery. Clinical applications of targeted therapies include prevention or treatment of recurrent disease after surgical resection of solid tumours. In vitro evaluation of 5F 203 prodrugs' activity demonstrated nanomolar potency against MCF-7 breast and IGROV-1 ovarian carcinoma cell lines. (C) 2015 Elsevier Ltd. All rights reserved.
C1 [Stone, Erica L.; Citossi, Francesca; Stevens, Malcolm F. G.; Stocks, Michael; Kellam, Barrie; Marlow, Maria; Bradshaw, Tracey D.] Univ Nottingham, Sch Pharm, Nottingham NG7 2RD, England.
[Singh, Rajinder; Kaur, Balvinder; Gaskell, Margaret; Farmer, Peter B.] Univ Leicester, Bioctr, Leicester LE1 7RH, Leics, England.
[Monks, Anne; Hose, Curtis] NCI, Frederick, MD 21702 USA.
[Leong, Chee-Onn] Int Med Univ, Sch Pharm & Hlth Sci, Kuala Lumpur 57000, Malaysia.
RP Bradshaw, TD (reprint author), Univ Nottingham, Sch Pharm, Nottingham NG7 2RD, England.
OI Stocks, Michael/0000-0003-3046-137X; Marlow, Maria/0000-0002-0333-5290
FU University of Nottingham, UK
FX Authors thanks the University of Nottingham, UK for studentships (E.L.S.
and F.C.) funding, and are grateful to colleagues at NCI and the
University of Leicester for collaborations.
NR 44
TC 6
Z9 6
U1 4
U2 11
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0968-0896
EI 1464-3391
J9 BIOORGAN MED CHEM
JI Bioorg. Med. Chem.
PD NOV 1
PY 2015
VL 23
IS 21
BP 6891
EP 6899
DI 10.1016/j.bmc.2015.09.052
PG 9
WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry,
Organic
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry
GA CV7FI
UT WOS:000364437400012
PM 26474663
ER
PT J
AU Hamano, R
Wu, XQ
Wang, YT
Oppenheim, JJ
Chen, X
AF Hamano, Ryoko
Wu, Xueqiang
Wang, Yitao
Oppenheim, Joost J.
Chen, Xin
TI Characterization of MT-2 cells as a human regulatory T cell-like cell
line
SO CELLULAR & MOLECULAR IMMUNOLOGY
LA English
DT Editorial Material
C1 [Hamano, Ryoko; Wu, Xueqiang; Oppenheim, Joost J.; Chen, Xin] NCI, Mol Immunoregulat Lab, Canc Inflammat Program, Ctr Canc Res, Frederick, MD 21701 USA.
[Hamano, Ryoko] Kanazawa Univ, Div Rheumatol, Kanazawa, Ishikawa, Japan.
[Wang, Yitao; Chen, Xin] Univ Macau, State Key Lab Qual Res Chinese Med, Inst Chinese Med Sci, Macau, Peoples R China.
RP Chen, X (reprint author), Univ Macau, Rm 7039,Bldg N22,Ave Univ, Taipa, Macau, Peoples R China.
EM xchen@umac.mo
RI Chen, Xin/I-6601-2015; Wang, Yitao/O-5184-2016
OI Chen, Xin/0000-0002-2628-4027;
FU Intramural NIH HHS
NR 10
TC 4
Z9 4
U1 1
U2 3
PU CHIN SOCIETY IMMUNOLOGY
PI BEING
PA 5 DONGDAN SANTIAO, DONGCHEN DISTRICT, BEING, 100005, PEOPLES R CHINA
SN 1672-7681
EI 2042-0226
J9 CELL MOL IMMUNOL
JI Cell. Mol. Immunol.
PD NOV
PY 2015
VL 12
IS 6
BP 780
EP 782
DI 10.1038/cmi.2014.123
PG 3
WC Immunology
SC Immunology
GA CV8HO
UT WOS:000364523600015
PM 25544500
ER
PT J
AU Cooper, LB
Mentz, RJ
Sun, JL
Schulte, PJ
Fleg, JL
Cooper, LS
Pina, IL
Leifer, ES
Kraus, WE
Whellan, DJ
Keteyian, SJ
O'Connor, CM
AF Cooper, Lauren B.
Mentz, Robert J.
Sun, Jie-Lena
Schulte, Phillip J.
Fleg, Jerome L.
Cooper, Lawton S.
Pina, Ileana L.
Leifer, Eric S.
Kraus, William E.
Whellan, David J.
Keteyian, Steven J.
O'Connor, Christopher M.
TI Psychosocial Factors, Exercise Adherence, and Outcomes in Heart Failure
Patients Insights From Heart Failure: A Controlled Trial Investigating
Outcomes of Exercise Training (HF-ACTION)
SO CIRCULATION-HEART FAILURE
LA English
DT Article
DE exercise; exercise therapy; heart failure; patients; social support
ID RANDOMIZED CONTROLLED-TRIAL; PERCEIVED SOCIAL SUPPORT; DEPRESSIVE
SYMPTOMS; CLINICAL-OUTCOMES; HEALTH-STATUS; MYOCARDIAL-INFARCTION;
PHYSICAL-ACTIVITY; 1ST YEAR; MORTALITY; HOSPITALIZATION
AB Background-Psychosocial factors may influence adherence with exercise training for heart failure (HF) patients. We aimed to describe the association between social support and barriers to participation with exercise adherence and clinical outcomes.
Methods and Results-Of patients enrolled in Heart Failure: A Controlled Trial Investigating Outcomes of Exercise Training (HF-ACTION), 2279 (97.8%) completed surveys to assess social support and barriers to exercise, resulting in the perceived social support score (PSSS) and barriers to exercise score (BTES). Higher PSSS indicated higher levels of social support, whereas higher BTES indicated more barriers to exercise. Exercise time at 3 and 12 months correlated with PSSS (r= 0.09 and r= 0.13, respectively) and BTES (r=-0.11 and r=-0.12, respectively), with higher exercise time associated with higher PSSS and lower BTES (All P<0.005). For cardiovascular death or HF hospitalization, there was a significant interaction between the randomization group and BTES (P=0.035), which corresponded to a borderline association between increasing BTES and cardiovascular death or HF hospitalization in the exercise group (hazard ratio 1.25, 95% confidence interval 0.99, 1.59), but no association in the usual care group (hazard ratio 0.83, 95% confidence interval 0.66, 1.06).
Conclusions-Poor social support and high barriers to exercise were associated with lower exercise time. PSSS did not impact the effect of exercise training on outcomes. However, for cardiovascular death or HF hospitalization, exercise training had a greater impact on patients with lower BTES. Given that exercise training improves outcomes in HF patients, assessment of perceived barriers may facilitate individualized approaches to implement exercise training therapy in clinical practice.
C1 [Cooper, Lauren B.; Mentz, Robert J.; Sun, Jie-Lena; Schulte, Phillip J.; O'Connor, Christopher M.] Duke Univ, Sch Med, Duke Clin Res Inst, Durham, NC USA.
[Cooper, Lauren B.; Mentz, Robert J.; Kraus, William E.; O'Connor, Christopher M.] Duke Univ, Sch Med, Dept Med, Durham, NC 27706 USA.
[Fleg, Jerome L.; Cooper, Lawton S.; Leifer, Eric S.] NHLBI, Div Cardiovasc Sci, Bethesda, MD 20892 USA.
[Pina, Ileana L.] Albert Einstein Coll Med, Div Cardiol, Bronx, NY 10467 USA.
[Whellan, David J.] Thomas Jefferson Univ, Jefferson Med Coll, Div Cardiol, Philadelphia, PA 19107 USA.
[Keteyian, Steven J.] Henry Ford Hosp, Div Cardiovasc Med, Detroit, MI 48202 USA.
RP Cooper, LB (reprint author), Duke Clin Res Inst, POB 17969, Durham, NC 27715 USA.
EM lauren.b.cooper@duke.edu
FU National Institutes of Health; National Institute of Health
[T32HL069749-11A1]
FX HF-ACTION was funded by the National Institutes of Health. Dr Cooper is
supported by grant T32HL069749-11A1 from the National Institute of
Health.
NR 30
TC 4
Z9 4
U1 1
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1941-3289
EI 1941-3297
J9 CIRC-HEART FAIL
JI Circ.-Heart Fail.
PD NOV
PY 2015
VL 8
IS 6
BP 1044
EP 1051
DI 10.1161/CIRCHEARTFAILURE.115.002327
PG 8
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA CW1SQ
UT WOS:000364772000005
PM 26578668
ER
PT J
AU Shah, AM
Claggett, B
Sweitzer, NK
Shah, SJ
Deswal, A
Anand, IS
Fleg, JL
Pitt, B
Pfeffer, MA
Solomon, SD
AF Shah, Amil M.
Claggett, Brian
Sweitzer, Nancy K.
Shah, Sanjiv J.
Deswal, Anita
Anand, Inder S.
Fleg, Jerome L.
Pitt, Bertram
Pfeffer, Marc A.
Solomon, Scott D.
TI Prognostic Importance of Changes in Cardiac Structure and Function in
Heart Failure With Preserved Ejection Fraction and the Impact of
Spironolactone
SO CIRCULATION-HEART FAILURE
LA English
DT Article
DE clinical trial; echocardiography; heart failure with preserved ejection
fraction; spironolactone
ID RANDOMIZED CONTROLLED-TRIAL; ALDOSTERONE ANTAGONIST TRIAL;
PULMONARY-HYPERTENSION; EXERCISE CAPACITY; PHOSPHODIESTERASE-5
INHIBITION; EUROPEAN-ASSOCIATION; DIASTOLIC FUNCTION; AMERICAN-SOCIETY;
TOPCAT TRIAL; DYSFUNCTION
AB Background-Limited data exist regarding the impact of aldosterone antagonist therapy on cardiac structure and function in heart failure with preserved ejection fraction and on the prognostic relevance of changes in cardiac structure and function in heart failure with preserved ejection fraction.
Methods and Results-Cardiac structure and function were assessed by quantitative echocardiography at baseline and at 12- to 18-month follow-up in 239 patients with heart failure with preserved ejection fraction (left ventricular [LV] ejection fraction [LVEF] 45%) enrolled in the Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist (TOPCAT) trial. The impact of spironolactone therapy on measures of cardiac structure and function was assessed in the study population overall, and change in echocardiographic measures was associated with the subsequent occurrence of the primary composite outcome of cardiovascular death, heart failure hospitalization, or aborted cardiac arrest. Spironolactone was not associated with alterations in cardiac structure and function compared with placebo. Decrease in left atrial volume at follow-up was associated with a lower risk of subsequent occurrence of the primary outcome.
Conclusions-Twelve to 18 months of spironolactone therapy was not associated with alterations in cardiac structure or function in patients with heart failure with preserved ejection fraction. Reduction in left atrial volume at follow-up was associated with a lower risk of subsequent occurrence of the primary composite outcome.
C1 [Shah, Amil M.; Claggett, Brian; Pfeffer, Marc A.; Solomon, Scott D.] Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA.
[Sweitzer, Nancy K.] Univ Arizona, Coll Med, Div Cardiol, Sarver Heart Ctr, Tucson, AZ USA.
[Shah, Sanjiv J.] Northwestern Univ, Div Cardiol, Feinberg Sch Med, Chicago, IL 60611 USA.
[Deswal, Anita] Michael E DeBakey VA Med Ctr, Div Cardiol, Houston, TX USA.
[Deswal, Anita] Baylor Coll Med, Houston, TX 77030 USA.
[Anand, Inder S.] VA Med Ctr, Div Cardiovasc, Minneapolis, MN USA.
[Fleg, Jerome L.] NHLBI, Bethesda, MD 20892 USA.
[Pitt, Bertram] Univ Michigan, Sch Med, Div Cardiol, Ann Arbor, MI USA.
RP Shah, AM (reprint author), Brigham & Womens Hosp, Div Cardiovasc Med, 75 Francis St, Boson, MA 02445 USA.
EM ashah11@partners.org
FU National Heart, Lung, and Blood Institute (NHLBI), National Institutes
of Health (Bethesda, MD) [HHSN268200425207C]; NHLBI [1K08HL116792];
American Heart Association grant [14CRP20380422]
FX TOPCAT was funded by National Heart, Lung, and Blood Institute (NHLBI),
National Institutes of Health (Bethesda, MD), Contract Number
HHSN268200425207C. The content of this article does not necessarily
represent the views of the sponsor or of the Department of Health and
Human Services. The work for this article was also supported by NHLBI
grant 1K08HL116792 (A.M. Shah) and American Heart Association grant
14CRP20380422 (A.M. Shah).
NR 26
TC 8
Z9 9
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1941-3289
EI 1941-3297
J9 CIRC-HEART FAIL
JI Circ.-Heart Fail.
PD NOV
PY 2015
VL 8
IS 6
BP 1052
EP 1058
DI 10.1161/CIRCHEARTFAILURE.115.002249
PG 7
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA CW1SQ
UT WOS:000364772000006
PM 26475142
ER
PT J
AU Kennedy, DJ
Shrestha, K
Sheehey, B
Li, XS
Guggilam, A
Wu, YP
Finucan, M
Gabi, A
Medert, CM
Westfall, K
Borowski, A
Fedorova, O
Bagrov, AY
Tang, WHW
AF Kennedy, David J.
Shrestha, Kevin
Sheehey, Brendan
Li, Xinmin S.
Guggilam, Anuradha
Wu, Yuping
Finucan, Michael
Gabi, Alaa
Medert, Charles M.
Westfall, Kristen
Borowski, Allen
Fedorova, Olga
Bagrov, Alexei Y.
Tang, W. H. Wilson
TI Elevated Plasma Marinobufagenin, An Endogenous Cardiotonic Steroid, Is
Associated With Right Ventricular Dysfunction and Nitrative Stress in
Heart Failure
SO CIRCULATION-HEART FAILURE
LA English
DT Article
DE cardiac fibrosis; cardiotonic steroids; heart failure; nitrative stress;
outcome
ID ACUTE MYOCARDIAL-INFARCTION; EXPERIMENTAL UREMIC CARDIOMYOPATHY;
DIGOXIN-LIKE IMMUNOREACTIVITY; NACL-SENSITIVE HYPERTENSION; SODIUM-PUMP;
CARDIAC-HYPERTROPHY; ATPASE INHIBITION; RENAL-FAILURE; OUABAIN;
DIGITALIS
AB Background-Plasma levels of cardiotonic steroids are elevated in volume-expanded states, such as chronic kidney disease, but the role of these natriuretic hormones in subjects with heart failure (HF) is unclear. We sought to determine the prognostic role of the cardiotonic steroids marinobufagenin (MBG) in HF, particularly in relation to long-term outcomes.
Methods and Results-We first measured plasma MBG levels and performed comprehensive clinical, laboratory, and echocardiographic assessment in 245 patients with HF. All-cause mortality, cardiac transplantation, and HF hospitalization were tracked for 5 years. In our study cohort, median (interquartile range) MBG was 583 (383-812) pM. Higher MBG was associated with higher myeloperoxidase (r=0.42, P<0.0001), B-type natriuretic peptide (r=0.25, P=0.001), and asymmetrical dimethylarginine (r=0.32, P<0.001). Elevated levels of MBG were associated with measures of worse right ventricular function (RV s', r=-0.39, P<0.0001) and predicted increased risk of adverse clinical outcomes (MBG574 pmol/L: hazard ratio 1.58 [1.10-2.31], P=0.014) even after adjustment for age, sex, diabetes mellitus, and ischemic pathogenesis. In mice, a left anterior descending coronary artery ligation model of HF lead to increases in MBG, whereas infusion of MBG into mice for 4 weeks lead to significant increases in myeloperoxidase, asymmetrical dimethylarginine, and cardiac fibrosis.
Conclusions-In the setting of HF, elevated plasma levels of MBG are associated with right ventricular dysfunction and predict worse long-term clinical outcomes in multivariable models adjusting for established clinical and biochemical risk factors. Infusion of MBG seems to directly contribute to increased nitrative stress and cardiac fibrosis.
C1 [Kennedy, David J.; Shrestha, Kevin; Sheehey, Brendan; Li, Xinmin S.; Guggilam, Anuradha; Wu, Yuping; Finucan, Michael; Gabi, Alaa; Medert, Charles M.; Westfall, Kristen; Borowski, Allen; Tang, W. H. Wilson] Cleveland Clin, Dept Cellular & Mol Med, Cleveland, OH 44106 USA.
[Tang, W. H. Wilson] Cleveland Clin, Ctr Cardiovasc Diagnost & Prevent, Lerner Res Inst, Cleveland, OH 44106 USA.
[Kennedy, David J.] Cleveland Clin, Glickman Urol & Kidney Inst, Dept Hypertens & Nephrol, Cleveland, OH 44106 USA.
[Tang, W. H. Wilson] Cleveland Clin, Inst Heart & Vasc, Dept Cardiovasc Med, Cleveland, OH 44106 USA.
[Fedorova, Olga; Bagrov, Alexei Y.] NIA, Cardiovasc Sci Lab, Hypertens Unit, NIH, Baltimore, MD 21224 USA.
RP Tang, WHW (reprint author), 9500 Euclid Ave,Desk J3-4, Cleveland, OH 44195 USA.
EM tangw@ccf.org
FU National Institutes of Health (NIH) [R01HL103931]; NIH/Office of Dietary
Supplements [P20HL113452]; Cleveland Clinic Clinical Research Unit of
the Case Western Reserve University CTSA [UL1TR 000439]; American Heart
Association Scientist Development Grant [14SDG18650010]; Intramural
Research Program, National Institute on Aging, National Institutes of
Health
FX This research was supported by grants from the National Institutes of
Health (NIH, R01HL103931) and the NIH/Office of Dietary Supplements
(P20HL113452) and the Cleveland Clinic Clinical Research Unit of the
Case Western Reserve University CTSA (UL1TR 000439). Dr Kennedy was
supported by an American Heart Association Scientist Development Grant
14SDG18650010. Drs Fedorova and Bagrov are supported by Intramural
Research Program, National Institute on Aging, National Institutes of
Health. Mass spectrometry studies were performed on instruments housed
in a facility supported in part by a Center of Innovations Award by AB
SCIEX.
NR 49
TC 2
Z9 4
U1 1
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1941-3289
EI 1941-3297
J9 CIRC-HEART FAIL
JI Circ.-Heart Fail.
PD NOV
PY 2015
VL 8
IS 6
BP 1068
EP 1076
DI 10.1161/CIRCHEARTFAILURE.114.001976
PG 9
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA CW1SQ
UT WOS:000364772000008
PM 26276886
ER
PT J
AU Olanich, ME
Sun, W
Hewitt, SM
Abdullaev, Z
Pack, SD
Barr, FG
AF Olanich, Mary E.
Sun, Wenyue
Hewitt, Stephen M.
Abdullaev, Zied
Pack, Svetlana D.
Barr, Frederic G.
TI CDK4 Amplification Reduces Sensitivity to CDK4/6 Inhibition in
Fusion-Positive Rhabdomyosarcoma
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID ALVEOLAR RHABDOMYOSARCOMA; CELL-CYCLE; TARGET GENES; IN-VITRO; TUMOR;
CANCER; E2F; RESISTANCE; SENESCENCE; EXPRESSION
AB Purpose: Rhabdomyosarcoma (RMS) is the most common pediatric soft tissue sarcoma and includes a PAX3- or PAX7-FOXO1 fusion-positive subtype. Amplification of chromosomal region 12q13-q14, which contains the CDK4 proto-oncogene, was identified in an aggressive subset of fusion-positive RMS. CDK4/6 inhibitors have antiproliferative activity in CDK4-amplified liposarcoma and neuroblastoma, suggesting CDK4/6 inhibition as a potential therapeutic strategy in fusion-positive RMS.
Experimental Design: We examined the biologic consequences of CDK4 knockdown, CDK4 overexpression, and pharmacologic CDK4/6 inhibition by LEE011 in fusion-positive RMS cell lines and xenografts.
Results: Knockdown of CDK4 abrogated proliferation and transformation of 12q13-14-amplified and nonamplified fusion-positive-RMS cells viaG1-phase cell-cycle arrest. This arrest was mediated by reduced RB phosphorylation and E2F-responsive gene expression. Significant differences in E2F target expression, cell-cycle distribution, proliferation, or transformation were not observed in RMS cells over expressing CDK4. Treatment with LEE011 phenocopied CDK4 knockdown, decreasing viability, RB phosphorylation, and E2F-responsive gene expression and inducing G1-phase cell-cycle arrest. Although all fusion-positive cell lines showed sensitivity to CDK4/6 inhibition, there was diminished sensitivity associated with CDK4 amplification and overexpression. This variable responsiveness to LEE011 was recapitulated in xenograft models ofCDK4-amplified and nonamplified fusion-positive RMS.
Conclusions: Our data demonstrate that CDK4 is necessary but overexpression is not sufficient for RB-E2F-mediated G1-phase cell-cycle progression, proliferation, and transformation in fusion-positive RMS. Our studies indicate that LEE011 is active in the setting of fusion-positive RMS and suggest that low CDK4-expressing fusion-positive tumors may be particularly susceptible to CDK4/6 inhibition. (C) 2015 AACR.
C1 [Olanich, Mary E.; Sun, Wenyue; Barr, Frederic G.] NCI, Canc Mol Pathol Sect, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Hewitt, Stephen M.] NCI, Tissue Array Res Program, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Hewitt, Stephen M.] NCI, Appl Mol Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Abdullaev, Zied; Pack, Svetlana D.] NCI, Chromosome Pathol Unit, Pathol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
RP Barr, FG (reprint author), NCI, Pathol Lab, Ctr Canc Res, 10 Ctr Dr,Room 3B55, Bethesda, MD 20892 USA.
EM barrfg@mail.nih.gov
OI Hewitt, Stephen/0000-0001-8283-1788
FU Intramural Research Program of the National Cancer Institute; Joanna
McAfee Childhood Cancer Foundation
FX This research was supported by the Intramural Research Program of the
National Cancer Institute and by the Joanna McAfee Childhood Cancer
Foundation.
NR 50
TC 4
Z9 4
U1 0
U2 1
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
EI 1557-3265
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD NOV 1
PY 2015
VL 21
IS 21
BP 4947
EP 4959
DI 10.1158/1078-0432.CCR-14-2955
PG 13
WC Oncology
SC Oncology
GA CV7WW
UT WOS:000364488100023
PM 25810375
ER
PT J
AU Wang, BD
Ceniccola, K
Yang, Q
Andrawis, R
Patel, V
Ji, Y
Rhim, J
Olender, J
Popratiloff, A
Latham, P
Lai, Y
Patierno, SR
Lee, NH
AF Wang, Bi-Dar
Ceniccola, Kristin
Yang, Qi
Andrawis, Ramez
Patel, Vyomesh
Ji, Youngmi
Rhim, Johng
Olender, Jacqueline
Popratiloff, Anastas
Latham, Patricia
Lai, Yinglei
Patierno, Steven R.
Lee, Norman H.
TI Identification and Functional Validation of Reciprocal microRNA-mRNA
Pairings in African American Prostate Cancer Disparities
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID RENAL-CELL CARCINOMA; BREAST-CANCER; EXPRESSION; MIR-96; TARGETS;
GROWTH; LOCUS; DEREGULATION; ASSOCIATION; PATHWAYS
AB Purpose: African Americans (AA) exhibit higher rates of prostate cancer incidence and mortality compared with European American (EA) men. In addition to socioeconomic influences, biologic factors are believed to play a critical role in prostate cancer disparities. We investigated whether population-specific and -enriched miRNA-mRNA interactions might contribute to prostate cancer disparities.
Experimental Design: Integrative genomics was used, combining miRNA and mRNA profiling, miRNA target prediction, pathway analysis, and functional validation, to map miRNA-mRNA interactions associated with prostate cancer disparities.
Results: We identified 22 AA-specific and 18 EA-specific miRNAs in prostate cancer versus patient-matched normal prostate, and 10 "AA-enriched/-depleted" miRNAs in AA prostate cancer versus EA prostate cancer comparisons. Manyof these populationspecific/-enriched miRNAs could be paired with target mRNAs that exhibited an inverse pattern of differential expression. Pathway analysis revealed EGFR (or ERBB) signaling as a critical pathway significantly regulated by AA-specific/-enriched mRNAs and miRNA-mRNApairings. Novel miRNA-mRNApairings were validated by qRT-PCR, Western blot, and/or IHC analyses in prostate cancer specimens. Loss/gain of function assays performed in population-specific prostate cancer cell lines confirmed miR-133a/MCL1, miR-513c/STAT1, miR-96/FOXO3A, miR-145/ITPR2, and miR-34a/PPP2R2A as critical miRNA-mRNA pairings driving oncogenesis. Manipulating the balance of these pairings resulted in decreased proliferation and invasion, and enhanced sensitization to docetaxel-induced cytotoxicity in AA prostate cancer cells.
Conclusions: Our data suggest that AA-specific/-enriched miRNA-mRNA pairings may play a critical role in the activation of oncogenic pathways in AA prostate cancer. Our findings also suggest that miR-133a/MCL1, miR-513c/STAT1, and miR-96/FOXO3A may have clinical significance in the development of novel strategies for treating aggressive prostate cancer. (C) 2015 AACR.
C1 [Wang, Bi-Dar; Ceniccola, Kristin; Yang, Qi; Olender, Jacqueline; Lee, Norman H.] George Washington Univ, Sch Med & Hlth Sci, Dept Pharmacol & Physiol, Washington, DC 20037 USA.
[Andrawis, Ramez] George Washington Univ, Sch Med & Hlth Sci, Med Fac Associates, Washington, DC 20037 USA.
[Patel, Vyomesh] Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD USA.
[Ji, Youngmi] NIAMSD, Cartilage Biol & Orthoped Branch, NIH, Bethesda, MD 20892 USA.
[Rhim, Johng] Uniformed Serv Univ Hlth Sci, Dept Surg, Ctr Prostate Dis Res, Bethesda, MD 20814 USA.
[Popratiloff, Anastas] George Washington Univ, Sch Med & Hlth Sci, Dept Anat & Regenerat Biol, Washington, DC 20037 USA.
[Latham, Patricia] George Washington Univ, Sch Med & Hlth Sci, Dept Pathol, Washington, DC 20037 USA.
[Lai, Yinglei] George Washington Univ, Dept Stat, Washington, DC 20037 USA.
[Patierno, Steven R.] George Washington Univ, Med Ctr, GW Canc Inst, Washington, DC 20037 USA.
[Patierno, Steven R.] Duke Univ, Med Ctr, Duke Canc Inst, Durham, NC USA.
RP Lee, NH (reprint author), George Washington Univ, Sch Med & Hlth Sci, 2300 I St North West, Washington, DC 20037 USA.
EM nhlee@gwu.edu
FU NCI grant [R01 CA120316]; DOD grant [PC121975]; Affymetrix
Collaborations in Cancer Research Award; NCI supplement grant [U01
CA116937]; American Cancer Society grant [IRG-08-091-01]
FX This work was supported by NCI grant R01 CA120316 (to N.H. Lee), DOD
grant PC121975 (to N.H. Lee), Affymetrix Collaborations in Cancer
Research Award (to N.H. Lee), NCI supplement grant U01 CA116937 (to S.R.
Patierno), and American Cancer Society grant IRG-08-091-01 (to B.-D.
Wang).
NR 50
TC 5
Z9 5
U1 2
U2 7
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
EI 1557-3265
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD NOV 1
PY 2015
VL 21
IS 21
BP 4970
EP 4984
DI 10.1158/1078-0432.CCR-14-1566
PG 15
WC Oncology
SC Oncology
GA CV7WW
UT WOS:000364488100025
PM 26089375
ER
PT J
AU Schoenbaum, M
AF Schoenbaum, Michael
TI INCREASING SUPPLY OF AND DEMAND FOR EVIDENCE-BASED PSYCHOTHERAPY:
NEAR-TERM OPTIONS FOR PAYERS AND POLICYMAKERS
SO DEPRESSION AND ANXIETY
LA English
DT Editorial Material
C1 NIMH, Off Sci Policy Planning & Commun, Bethesda, MD 20892 USA.
RP Schoenbaum, M (reprint author), NIMH, Off Sci Policy Planning & Commun, 6001 Execut Blvd,MSC 9669, Bethesda, MD 20892 USA.
EM schoenbaumm@mail.nih.gov
NR 10
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1091-4269
EI 1520-6394
J9 DEPRESS ANXIETY
JI Depress. Anxiety
PD NOV
PY 2015
VL 32
IS 11
BP 809
EP 810
DI 10.1002/da.22442
PG 2
WC Psychology, Clinical; Psychiatry; Psychology
SC Psychology; Psychiatry
GA CV6PM
UT WOS:000364392300010
PM 26502366
ER
PT J
AU Thievessen, I
Fakhri, N
Steinwachs, J
Kraus, V
McIsaac, RS
Gao, L
Chen, BC
Baird, MA
Davidson, MW
Betzig, E
Oldenbourg, R
Waterman, CM
Fabry, B
AF Thievessen, Ingo
Fakhri, Nikta
Steinwachs, Julian
Kraus, Viola
McIsaac, R. Scott
Gao, Liang
Chen, Bi-Chang
Baird, Michelle A.
Davidson, Michael W.
Betzig, Eric
Oldenbourg, Rudolf
Waterman, Clare M.
Fabry, Ben
TI Vinculin is required for cell polarization, migration, and extracellular
matrix remodeling in 3D collagen
SO FASEB JOURNAL
LA English
DT Article
DE 3D cell migration; cell morphodynamics; traction force generation;
integrin
ID BIOPOLYMER NETWORKS; ADHESION; FORCE; TISSUE; MORPHOGENESIS;
FIBRONECTIN; TENSION; RECRUITMENT; MOVEMENT; DYNAMICS
AB Vinculin is filamentous (F)-actin-binding protein enriched in integrin-based adhesions to the extracellular matrix (ECM). Whereas studies in 2-dimensional (2D) tissue culture models have suggested that vinculin negatively regulates cell migration by promoting cytoskeleton-ECM coupling to strengthen and stabilize adhesions, its role in regulating cell migration in more physiologic, 3-dimensional (3D) environments is unclear. To address the role of vinculin in 3D cell migration, we analyzed the morphodynamics, migration, and ECM remodeling of primary murine embryonic fibroblasts (MEFs) with cre/loxP-mediated vinculin gene disruption in 3D collagen I cultures. We found that vinculin promoted 3D cell migration by increasing directional persistence. Vinculin was necessary for persistent cell protrusion, cell elongation, and stable cell orientation in 3D collagen, but was dispensable for lamellipodia formation, suggesting that vinculin-mediated cell adhesion to the ECM is needed to convert actin-based cell protrusion into persistent cell shape change and migration. Consistent with this finding, vinculin was necessary for efficient traction force generation in 3D collagen without affecting myosin II activity and promoted 3D collagen fiber alignment and macroscopical gel contraction. Our results suggest that vinculin promotes directionally persistent cell migration and tension-dependent ECM remodeling in complex 3D environments by increasing cell-ECM adhesion and traction force generation.
C1 [Thievessen, Ingo; Waterman, Clare M.] NHLBI, Lab Cell & Tissue Morphodynam, Cell Biol & Physiol Ctr, NIH, Bethesda, MD 20892 USA.
[Thievessen, Ingo; Steinwachs, Julian; Kraus, Viola; Fabry, Ben] Univ Erlangen Nurnberg, Biophys Grp, Dept Phys, D-91054 Erlangen, Germany.
[Thievessen, Ingo; Fakhri, Nikta; McIsaac, R. Scott; Gao, Liang; Chen, Bi-Chang; Baird, Michelle A.; Davidson, Michael W.; Betzig, Eric; Waterman, Clare M.] Marine Biol Lab, Physiol Course, Woods Hole, MA 02543 USA.
[Oldenbourg, Rudolf] Marine Biol Lab, Cellular Dynam Program, Woods Hole, MA 02543 USA.
[Fakhri, Nikta] Univ Gottingen, Phys Inst Biophys 3, D-37073 Gottingen, Germany.
[Fakhri, Nikta] MIT, Dept Phys, Phys Living Syst, Cambridge, MA 02139 USA.
[McIsaac, R. Scott] Princeton Univ, Lewis Sigler Inst Integrat Genom, Princeton, NJ 08544 USA.
[McIsaac, R. Scott] Calif Life Co, San Francisco, CA USA.
[Gao, Liang; Chen, Bi-Chang; Betzig, Eric] Howard Hughes Med Inst, Ashburn, VA USA.
[Gao, Liang] SUNY Stony Brook, Dept Chem, Stony Brook, NY 11794 USA.
[Chen, Bi-Chang] Acad Sinica, Res Ctr Appl Sci, Taipei 115, Taiwan.
[Baird, Michelle A.; Davidson, Michael W.] Florida State Univ, Dept Biol Sci, Natl High Magnet Field Lab, Tallahassee, FL 32306 USA.
RP Thievessen, I (reprint author), Univ Erlangen Nurnberg, Biophys Grp, Dept Phys, Henkestr 91, D-91054 Erlangen, Germany.
EM ithievessen@biomed.uni-erlangen.de
RI Chen , Bi-Chang /F-3480-2014; Fakhri, Nikta/B-4657-2008; Fabry,
Ben/C-5496-2013
OI Fakhri, Nikta/0000-0003-1261-7465; Fabry, Ben/0000-0003-1737-0465
FU NIH NHLBI Division of Intramural Research; Deutsche
Forschungsgemeinschaft; Human Frontier Science Program Fellowship; U.S.
National Science Foundation Graduate Research Fellowship Program
FX The authors thank the U.S. National Institutes of Health (NIH), National
Heart, Lung, and Blood Institute (NHLBI) Flow Cytometry Core Facility,
for fluorescence-activated cell sorting, Silvio Gutkind for adenovirus,
and Robert Fischer for helpful discussion. This work was supported by
the NIH NHLBI Division of Intramural Research (C.M.W. and I.T.),
Deutsche Forschungsgemeinschaft (B.F., I.T., and J.S.), the Human
Frontier Science Program Fellowship (N.F.), and the U.S. National
Science Foundation Graduate Research Fellowship Program (R.S.M.).
NR 41
TC 8
Z9 8
U1 3
U2 23
PU FEDERATION AMER SOC EXP BIOL
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0892-6638
EI 1530-6860
J9 FASEB J
JI Faseb J.
PD NOV
PY 2015
VL 29
IS 11
BP 4555
EP 4567
DI 10.1096/fj.14-268235
PG 13
WC Biochemistry & Molecular Biology; Biology; Cell Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics; Cell Biology
GA CV8EZ
UT WOS:000364514700015
PM 26195589
ER
PT J
AU Kirkby, NS
Reed, DM
Edin, ML
Rauzi, F
Mataragka, S
Vojnovic, I
Bishop-Bailey, D
Milne, GL
Longhurst, H
Zeldin, DC
Mitchell, JA
Warner, TD
AF Kirkby, Nicholas S.
Reed, Daniel M.
Edin, Matthew L.
Rauzi, Francesca
Mataragka, Stefania
Vojnovic, Ivana
Bishop-Bailey, David
Milne, Ginger L.
Longhurst, Hilary
Zeldin, Darryl C.
Mitchell, Jane A.
Warner, Timothy D.
TI Inherited human group IVA cytosolic phospholipase A(2) deficiency
abolishes platelet, endothelial, and leucocyte eicosanoid generation
SO FASEB JOURNAL
LA English
DT Article
DE cardiovascular; thromboxane A(2); prostacyclin; inflammation
ID 12-HYDROXYEICOSATETRAENOIC ACID; CARDIOVASCULAR-SYSTEM;
ARACHIDONIC-ACID; GLYCOPROTEIN-VI; BLOOD; 12-LIPOXYGENASE; BIOSYNTHESIS;
PROSTACYCLIN; ACTIVATION; RECEPTOR
AB Eicosanoids are important vascular regulators, but the phospholipase A(2) (PLA(2)) isoforms supporting their production within the cardiovascular system are not fully understood. To address this, we have studied platelets, endothelial cells, and leukocytes from 2 siblings with a homozygous loss-of-function mutation in group IVA cytosolic phospholipase A(2) (cPLA(2)alpha). Chromatography/mass spectrometry was used to determine levels of a broad range of eicosanoids produced by isolated vascular cells, and in plasma and urine. Eicosanoid release data were paired with studies of cellular function. Absence of cPLA(2)alpha almost abolished eicosanoid synthesis in platelets (e.g., thromboxane A(2), control 20.5 +/- 1.4 ng/ml vs. patient 0.1 ng/ml) and leukocytes [e.g., prostaglandin E-2 (PGE(2)), control 21.9 +/- 7.4 ng/ml vs. patient 1.9 ng/ml], and this was associated with impaired platelet activation and enhanced inflammatory responses. cPLA(2)alpha-deficient endothelial cells showed reduced, but not absent, formation of prostaglandin I-2 (prostacyclin; control 956 +/- 422 pg/ml vs. patient 196 pg/ml) and were primed for inflammation. In the urine, prostaglandin metabolites were selectively influenced by cPLA(2)alpha deficiency. For example, prostacyclin metabolites were strongly reduced (18.4% of control) in patients lacking cPLA(2)alpha, whereas PGE(2) metabolites (77.8% of control) were similar to healthy volunteer levels. These studies constitute a definitive account, demonstrating the fundamental role of cPLA(2)alpha to eicosanoid formation and cellular responses within the human circulation.
C1 [Kirkby, Nicholas S.; Reed, Daniel M.; Mataragka, Stefania; Mitchell, Jane A.] Univ London Imperial Coll Sci Technol & Med, Natl Heart & Lung Inst, London, England.
[Kirkby, Nicholas S.; Rauzi, Francesca; Vojnovic, Ivana; Warner, Timothy D.] Queen Mary Univ London, William Harvey Res Inst, London, England.
[Edin, Matthew L.; Zeldin, Darryl C.] NIEHS, NIH, Res Triangle Pk, NC 27709 USA.
[Bishop-Bailey, David] Univ London Royal Vet Coll, Dept Comparat Biomed Sci, London, England.
[Milne, Ginger L.] Vanderbilt Univ, Dept Pharmacol, Nashville, TN USA.
[Milne, Ginger L.] Vanderbilt Univ, Dept Med, Nashville, TN USA.
[Longhurst, Hilary] Barts Hlth, Immunol Dept, London, England.
[Longhurst, Hilary] London Natl Hlth Serv Trust, London, England.
RP Warner, TD (reprint author), Barts & London Queen Marys Sch Med & Dent, William Harvey Res Inst, Charterhouse Sq, London EC1M 6BQ, England.
EM t.d.warner@qmul.ac.uk
RI Warner, Timothy/A-1980-2009; Milne, Ginger/D-7648-2014;
OI Warner, Timothy/0000-0003-3988-4408; Milne, Ginger/0000-0003-3890-151X;
Edin, Matthew/0000-0002-7042-500X
FU Imperial College Junior Research Fellowship; Wellcome Trust program
grant [0852551Z108/Z]; British Heart Foundation Ph.D. studentship
[FS/10/033/28271]; British Heart Foundation project grant
[PG/11/39/28890]; Intramural Research Program of the U.S. National
Institutes of Health, National Institute of Environmental Health
Sciences [Z01 ES025034]
FX The authors acknowledge the cytosolic phospholipase A2-deficient
individuals who made these studies possible by volunteering to provide
blood samples. This research was supported by an Imperial College Junior
Research Fellowship (to N.S.K.), Wellcome Trust program grant
(0852551Z108/Z to J.A.M. and T.D.W.), British Heart Foundation Ph.D.
studentship (FS/10/033/28271 to F.R.), British Heart Foundation project
grant (PG/11/39/28890 to D.B.-B.), and by the Intramural Research
Program of the U.S. National Institutes of Health, National Institute of
Environmental Health Sciences (Z01 ES025034 to D.C.Z.).
NR 46
TC 3
Z9 3
U1 0
U2 3
PU FEDERATION AMER SOC EXP BIOL
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0892-6638
EI 1530-6860
J9 FASEB J
JI Faseb J.
PD NOV
PY 2015
VL 29
IS 11
BP 4568
EP 4578
DI 10.1096/fj.15-275065
PG 11
WC Biochemistry & Molecular Biology; Biology; Cell Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics; Cell Biology
GA CV8EZ
UT WOS:000364514700016
PM 26183771
ER
PT J
AU Cho, HY
Marzec, J
Kleeberger, SR
AF Cho, Hye-Youn
Marzec, Jacqui
Kleeberger, Steven R.
TI Functional polymorphisms in Nrf2: implications for human disease
SO FREE RADICAL BIOLOGY AND MEDICINE
LA English
DT Article
DE Somatic; Mutations; Complex disease; Genetic; Promoter; Antioxidant
response element; Mouse; Genome-wide association
ID NRF2-ENCODING NFE2L2 HAPLOTYPES; ANTIOXIDANT RESPONSE ELEMENTS;
SYSTEMIC-LUPUS-ERYTHEMATOSUS; GENE PROMOTER POLYMORPHISM; TRANSCRIPTION
FACTOR NRF2; SQUAMOUS-CELL CARCINOMAS; ACUTE LUNG INJURY; ANNUAL
DECLINE; BREAST-CANCER; E3 LIGASE
AB Nuclear factor (erythroid derived)-2 like 2 (NFE2L2), also known as nuclear factor erythroid 2 (NF-E2)-related factor 2 (Nrf2), is a ubiquitous transcription factor essential for protecting cells and tissues from oxidative stress-induced injury. Positional cloning and studies with Nrf2 knockout mice have identified important roles for this transcription factor in disease phenotypes for many organ systems. Studies have also characterized the means through which human Nrf2 is regulated and the mechanisms of interaction with antioxidant response elements (ARE) in promoters of effector genes. Moreover, single nucleotide polymorphisms (SNPs) in Nrf2 have been identified and evaluated for effects on gene expression and function, and translational investigations have sought to determine whether loss of function SNPs associate with disease progression. In this review, we present 1) an overview of the human Nrf2 gene and protein domain, 2) identification of genetic mutations in Nrf2 and associations of the mutations with multiple diseases, and 3) the role of somatic mutations in Nrf2 in diseases, primarily various cancers.
C1 [Cho, Hye-Youn; Marzec, Jacqui; Kleeberger, Steven R.] NIEHS, Inflammat Immun & Dis Lab, NIH, Res Triangle Pk, NC 27709 USA.
RP Kleeberger, SR (reprint author), NIEHS, Inflammat Immun & Dis Lab, NIH, 111 TW Alexander Dr,Bldg 101,MD D-201, Res Triangle Pk, NC 27709 USA.
EM kleeber1@niehs.nih.gov
FU Intramural Research Program of the National Institutes of Health,
National Institute of Environmental Health Sciences (NIEHS)
FX The research related to the manuscript was supported by the Intramural
Research Program of the National Institutes of Health, National
Institute of Environmental Health Sciences (NIEHS). Drs. Michael Fessler
and Donald Cook at the N1EHS provided excellent critical review of the
manuscript.
NR 80
TC 6
Z9 6
U1 2
U2 4
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 NOV
PY 2015
VL 88
BP 362
EP 372
DI 10.1016/j.freeradbiomed.2015.06.012
PN B
PG 11
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA CV0TN
UT WOS:000363966300024
PM 26117318
ER
PT J
AU Lacher, SE
Lee, JS
Wang, XT
Campbell, MR
Bell, DA
Slattery, M
AF Lacher, Sarah E.
Lee, Joslynn S.
Wang, Xuting
Campbell, Michelle R.
Bell, Douglas A.
Slattery, Matthew
TI Beyond antioxidant genes in the ancient Nrf2 regulatory network
SO FREE RADICAL BIOLOGY AND MEDICINE
LA English
DT Article
DE Nrf2; Keap1; ARE; Drosophila; Human; Genomics; Transcriptional
regulation; Enhancer; Free radicals
ID TRANSCRIPTION FACTOR NRF2; OXIDATIVE STRESS-ADAPTATION; HUMAN
NEUROBLASTOMA-CELLS; DIET-INDUCED OBESITY; DROSOPHILA-MELANOGASTER;
PYRUVATE-CARBOXYLASE; TERT-BUTYLHYDROQUINONE; ENRICHMENT ANALYSIS;
SIGNALING PATHWAY; FEEDBACK LOOP
AB Nrf2, a basic leucine zipper transcription factor encoded by the gene NFE2L2, is a master regulator of the transcriptional response to oxidative stress. Nrf2 is structurally and functionally conserved from insects to humans, and it heterodimerizes with the small MAF transcription factors to bind a consensus DNA sequence (the antioxidant response element, or ARE) and regulate gene expression. We have used genome-wide chromatin immunoprecipitation and gene expression data to identify direct Nrf2 target genes in Drosophila and humans. These data have allowed us to construct the deeply conserved ancient Nrf2 regulatory network target genes that are conserved from Drosophila to human. The ancient network consists of canonical antioxidant genes, as well as genes related to proteasomal pathways and metabolism and a number of less expected genes. We have also used enhancer reporter assays and electrophoretic mobility-shift assays to confirm Nrf2-mediated regulation of ARE activity at a number of these novel target genes. Interestingly, the ancient network also highlights a prominent negative feedback loop; this, combined with the finding that Nrf2-mediated regulatory output is tightly linked to the quality of the ARE it is targeting, suggests that precise regulation of nuclear Nrf2 concentration is necessary to achieve proper quantitative regulation of distinct gene sets. Together, these findings highlight the importance of balance in the Nrf2-ARE pathway and indicate that Nrf2-mediated regulation of xenobiotic metabolism, glucose metabolism, and proteostasis has been central to this pathway since its inception. (C) 2015 Published by Elsevier Inc.
C1 [Lacher, Sarah E.; Lee, Joslynn S.; Slattery, Matthew] Univ Minnesota, Sch Med, Dept Biomed Sci, Duluth, MN 55812 USA.
[Wang, Xuting; Campbell, Michelle R.; Bell, Douglas A.] NIEHS, Environm Genom Sect, Genome Integr & Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA.
[Slattery, Matthew] Univ Minnesota, Ctr Dev Biol, Minneapolis, MN 55455 USA.
RP Slattery, M (reprint author), Univ Minnesota, Sch Med, Dept Biomed Sci, Duluth, MN 55812 USA.
EM mslatter@umn.edu
OI Lee, Joslynn/0000-0001-9363-6013; Wang, Xuting/0000-0001-6781-8008
FU University of Minnesota Foundation; Intramural Research Program of the
National Institute of Environmental Health Sciences, National Institutes
of Health [Z01-ES-100475, ES065079]
FX The authors thank Evan Odean (University of Minnesota), Lijia Ma
(University of Chicago), Anshul Kundaje (Stanford), and Katherine Harris
(SwitchGear Genomics) for technical assistance. This work was supported
by funding from the University of Minnesota Foundation (M.S.) and the
Intramural Research Program of the National Institute of Environmental
Health Sciences, National Institutes of Health (Z01-ES-100475 and
ES065079 to D.A.B.).
NR 75
TC 5
Z9 7
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 NOV
PY 2015
VL 88
BP 452
EP 465
DI 10.1016/j.freeradbiomed.2015.06.044
PN B
PG 14
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA CV0TN
UT WOS:000363966300032
PM 26163000
ER
PT J
AU Shen, F
Mao, L
Zhu, W
Lawton, MT
Pechan, P
Colosi, P
Wu, Z
Scaria, A
Su, H
AF Shen, F.
Mao, L.
Zhu, W.
Lawton, M. T.
Pechan, P.
Colosi, P.
Wu, Z.
Scaria, A.
Su, H.
TI Inhibition of pathological brain angiogenesis through systemic delivery
of AAV vector expressing soluble FLT1
SO GENE THERAPY
LA English
DT Article
ID ENDOTHELIAL GROWTH-FACTOR; HEREDITARY HEMORRHAGIC TELANGIECTASIA;
ADULT-MOUSE BRAIN; ADENOASSOCIATED VIRUS; GENE-TRANSFER;
ARTERIOVENOUS-MALFORMATION; VASCULAR MALFORMATIONS; IMMUNE-RESPONSES;
VEGF; THERAPY
AB The soluble vascular endothelial growth factor (VEGF) receptor 1 (sFLT1) has been tested in both animals and humans for anti-angiogenic therapies, for example, age-related macular degeneration. We hypothesized that adeno-associated viral vector (AAV)mediated sFLT1 expression could be used to inhibit abnormal brain angiogenesis. We tested the anti-angiogenic effect of sFLT1 and the feasibility of using AAV serotype 9 to deliver sFLT1 through intravenous injection (IV) to the brain angiogenic region. AAVs were packaged in AAV serotypes 1 and 2 (stereotactic injection) and 9 (IV injection). Brain angiogenesis was induced in adult mice through stereotactic injection of AAV1-VEGF. AAV2-sFLT02 containing sFLT1 VEGF-binding domain (domain 2) was injected into the brain angiogenic region, and AAV9-sFLT1 was injected into the jugular vein at the time of or 4 weeks after AAV1-VEGF injection. We showed that AAV2-sFLT02 inhibited brain angiogenesis at both time points. IV injection of AAV9-sFLT1 inhibited angiogenesis only when the vector was injected 4 weeks after angiogenic induction. Neither lymphocyte infiltration nor neuron loss was observed in AAV9-sFLT1-treated mice. Our data show that systemically delivered AAV9-sFLT1 inhibits angiogenesis in the mouse brain, which could be utilized to treat brain angiogenic diseases such as brain arteriovenous malformation.
C1 [Shen, F.; Mao, L.; Zhu, W.; Su, H.] Univ Calif San Francisco, Dept Anesthesia & Perioperat Care, Ctr Cerebrovasc Res, San Francisco, CA 94110 USA.
[Shen, F.] Shanghai Jiao Tong Univ, Sch Med, Ruijin Hosp, Dept Neurol, Shanghai, Peoples R China.
[Lawton, M. T.] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA 94110 USA.
[Pechan, P.; Scaria, A.] Sanofi Genzyme R&D Ctr, Framingham, MA USA.
[Colosi, P.; Wu, Z.] NEI, Ocular Gene Therapy Core, NIH, Bethesda, MD 20892 USA.
RP Su, H (reprint author), Univ Calif San Francisco, Dept Anesthesia & Perioperat Care, 1001 Potrero Ave Box 1368, San Francisco, CA 94110 USA.
EM hua.su@ucsf.edu
FU National Institutes of Health [R01 NS027713, R01 HL122774, R21
NS070153]; Michael Ryan Zodda Foundation; UCSF Research Evaluation and
Allocation Committee (REAC); National Natural Science Foundation of
China [81471177]
FX We thank the members of the UCSF BAVM Study Project
(http://avm.ucsf.edu) for their support, and Voltaire Gungab for
assistance with manuscript preparation. This study was supported by
grants to H. Su from the National Institutes of Health (R01 NS027713,
R01 HL122774, and R21 NS070153) and from the Michael Ryan Zodda
Foundation and UCSF Research Evaluation and Allocation Committee (REAC),
and by a grant to F Shen from the National Natural Science Foundation of
China (No 81471177).
NR 60
TC 1
Z9 1
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0969-7128
EI 1476-5462
J9 GENE THER
JI Gene Ther.
PD NOV
PY 2015
VL 22
IS 11
BP 893
EP 900
DI 10.1038/gt.2015.57
PG 8
WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Genetics & Heredity; Medicine, Research & Experimental
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Genetics & Heredity; Research & Experimental Medicine
GA CV8YO
UT WOS:000364574500007
PM 26090874
ER
PT J
AU Singh, PK
Plumb, MR
Ferris, AL
Iben, JR
Wu, XL
Fadel, HJ
Luke, BT
Esnault, C
Poeschla, EM
Hughes, SH
Kvaratskhelia, M
Levin, HL
AF Singh, Parmit Kumar
Plumb, Matthew R.
Ferris, Andrea L.
Iben, James R.
Wu, Xiaolin
Fadel, Hind J.
Luke, Brian T.
Esnault, Caroline
Poeschla, Eric M.
Hughes, Stephen H.
Kvaratskhelia, Mamuka
Levin, Henry L.
TI LEDGF/p75 interacts with mRNA splicing factors and targets HIV-1
integration to highly spliced genes
SO GENES & DEVELOPMENT
LA English
DT Article
DE HIV-1; integration; mRNA splicing; LEDGF; p75; retrovirus
ID LEUKEMIA-VIRUS INTEGRATION; HUMAN-IMMUNODEFICIENCY-VIRUS; TRANSCRIPTION
START SITES; DNA INTEGRATION; HUMAN-CELLS; LENTIVIRAL INTEGRATION;
RETROVIRAL INTEGRATION; STRUCTURAL BASIS; MLV INTEGRATION; COACTIVATOR
P75
AB The host chromatin-binding factor LEDGF/p75 interacts with HIV-1 integrase and directs integration to active transcription units. To understand how LEDGF/p75 recognizes transcription units, we sequenced 1 million HIV-1 integration sites isolated from cultured HEK293T cells. Analysis of integration sites showed that cancer genes were preferentially targeted, raising concerns about using lentivirus vectors for gene therapy. Additional analysis led to the discovery that introns and alternative splicing contributed significantly to integration site selection. These correlations were independent of transcription levels, size of transcription units, and length of the introns. Multivariate analysis with five parameters previously found to predict integration sites showed that intron density is the strongest predictor of integration density in transcription units. Analysis of previously published HIV-1 integration site data showed that integration density in transcription units in mouse embryonic fibroblasts also correlated strongly with intron number, and this correlation was absent in cells lacking LEDGF. Affinity purification showed that LEDGF/p75 is associated with a number of splicing factors, and RNA sequencing (RNA-seq) analysis of HEK293T cells lacking LEDGF/p75 or the LEDGF/p75 integrase-binding domain (IBD) showed that LEDGF/p75 contributes to splicing patterns in half of the transcription units that have alternative isoforms. Thus, LEDGF/p75 interacts with splicing factors, contributes to exon choice, and directs HIV-1 integration to transcription units that are highly spliced.
C1 [Singh, Parmit Kumar; Esnault, Caroline; Levin, Henry L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Eukaryot Transposable Elements, Program Cellular Regulat & Metab, NIH, Bethesda, MD 20892 USA.
[Plumb, Matthew R.; Kvaratskhelia, Mamuka] Ohio State Univ, Coll Pharm, Ctr Retrovirus Res, Columbus, OH 43210 USA.
[Ferris, Andrea L.; Hughes, Stephen H.] NCI, HIV Drug Resistance Program, Frederick, MD 21702 USA.
[Iben, James R.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Genom Differentiat, NIH, Bethesda, MD 20892 USA.
[Wu, Xiaolin] Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
[Fadel, Hind J.] Mayo Clin, Coll Med, Dept Mol Med, Rochester, MN 55905 USA.
[Luke, Brian T.] Leidos Biomed Res Inc, Adv Biomed Comp Ctr, Frederick Natl Lab Canc Res, Frederick, MD USA.
[Poeschla, Eric M.] Univ Colorado, Div Infect Dis, Sch Med, Aurora, CO 80045 USA.
RP Levin, HL (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Eukaryot Transposable Elements, Program Cellular Regulat & Metab, NIH, Bethesda, MD 20892 USA.
EM henry_levin@nih.gov
FU Intramural Research Programs of the National Institutes of Health from
the Eunice Kennedy Shriver National Institute of Child Health and Human
Development; National Cancer Institute; National Institutes of Health
Intramural AIDS Targeted Antiviral Program; National Institutes of
Health [AI062520, AI77344]; National Cancer Institute
[HHSN261200800001E]
FX P.K.S. dedicates this article to his parents, Shri Dhurandhar Singh and
Smt. Sushila Devi. We thank Anthony Hickey for computational assistance.
We are grateful to Allen Kane for help in preparing the figures. This
research was supported by the Intramural Research Programs of the
National Institutes of Health from the Eunice Kennedy Shriver National
Institute of Child Health and Human Development (H.L.L.) and the
National Cancer Institute (S.H.H.). This research also received support
from the National Institutes of Health Intramural AIDS Targeted
Antiviral Program (H.L.L. and S.H.H.). The present study was also
supported by National Institutes of Health grants AI062520 (to M.K.) and
AI77344 (to E.M.P.). Funds from the National Cancer Institute under
contract number HHSN261200800001E to the Frederick National Laboratory
for Cancer Research (B.T.L.) were also used. P.K.S., M.R.P., A.L.F., and
H.J.F. designed and performed experiments and analyzed data. J.R.I.,
C.E., and X.W. provided computational expertise and analysis. E.M.P.,
S.H.H., M.K., and H.L.L. designed, supervised, and analyzed experiments.
B.T.L. and P.K.S. conducted the multivariate analyses. P.K.S. and H.L.L.
conceived the study and wrote the paper. All authors contributed to
editing of the paper.
NR 57
TC 10
Z9 10
U1 0
U2 2
PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
PI COLD SPRING HARBOR
PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA
SN 0890-9369
EI 1549-5477
J9 GENE DEV
JI Genes Dev.
PD NOV 1
PY 2015
VL 29
IS 21
BP 2287
EP 2297
DI 10.1101/gad.267609.115
PG 11
WC Cell Biology; Developmental Biology; Genetics & Heredity
SC Cell Biology; Developmental Biology; Genetics & Heredity
GA CW2WJ
UT WOS:000364853500007
PM 26545813
ER
PT J
AU Decker, B
Davis, BW
Rimbault, M
Long, AH
Karlins, E
Jagannathan, V
Reiman, R
Parker, HG
Drogemuller, C
Corneveaux, JJ
Chapman, ES
Trent, JM
Leeb, T
Huentelman, MJ
Wayne, RK
Karyadi, DM
Ostranderl, EA
AF Decker, Brennan
Davis, Brian W.
Rimbault, Maud
Long, Adrienne H.
Karlins, Eric
Jagannathan, Vidhya
Reiman, Rebecca
Parker, Heidi G.
Droegemueller, Cord
Corneveaux, Jason J.
Chapman, Erica S.
Trent, Jeffery M.
Leeb, Tosso
Huentelman, Matthew J.
Wayne, Robert K.
Karyadi, Danielle M.
Ostranderl, Elaine A.
TI Comparison against 186 canid whole-genome sequences reveals survival
strategies of an ancient clonally transmissible canine tumor
SO GENOME RESEARCH
LA English
DT Article
ID CLASS-I MOLECULES; ANTIGEN PRESENTATION; GRANZYME-B; IFN-GAMMA; CANCER;
ACTIVATION; APOPTOSIS; ORIGIN; AMINOPEPTIDASE; SUBSTITUTIONS
AB Canine transmissible venereal tumor (CTVT) is a parasitic cancer clone that has propagated for thousands of years via sexual transfer of malignant cells. Little is understood about the mechanisms that converted an ancient tumor into the world's oldest known continuously propagating somatic cell lineage. We created the largest existing catalog of canine genome-wide variation and compared it against two CTVT genome sequences, thereby separating alleles derived from the founder's genome from somatic mutations that must drive clonal transmissibility. We show that CTVT has undergone continuous adaptation to its transmissible allograft niche, with overlapping mutations at every step of immunosurveillance, particularly self-antigen presentation and apoptosis. We also identified chronologically early somatic mutations in oncogenesis- and immune-related genes that may represent key initiators of clonal transmissibility. Thus, we provide the first insights into the specific genomic aberrations that underlie CTVT's dogged perseverance in canids around the world.
C1 [Decker, Brennan; Davis, Brian W.; Rimbault, Maud; Karlins, Eric; Parker, Heidi G.; Chapman, Erica S.; Karyadi, Danielle M.; Ostranderl, Elaine A.] NHGRI, Canc Genet & Comparat Genom Branch, NIH, Bethesda, MD 20892 USA.
[Decker, Brennan] Univ Cambridge, Sch Clin Med, Dept Publ Hlth & Primary Care, Cambridge CB1 8RN, England.
[Long, Adrienne H.] NCI, Pediat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Jagannathan, Vidhya; Droegemueller, Cord; Leeb, Tosso] Univ Bern, Inst Genet, CH-3001 Bern, Switzerland.
[Reiman, Rebecca; Corneveaux, Jason J.; Trent, Jeffery M.; Huentelman, Matthew J.] Translat Genom Res Inst, Phoenix, AZ 85004 USA.
[Wayne, Robert K.] Univ Calif Los Angeles, Dept Ecol & Evolutionary Biol, Los Angeles, CA 90095 USA.
RP Ostranderl, EA (reprint author), NHGRI, Canc Genet & Comparat Genom Branch, NIH, Bethesda, MD 20892 USA.
EM eostrand@mail.nih.gov
OI Davis, Brian/0000-0002-6121-135X; Decker, Brennan/0000-0003-4516-7421;
Drogemuller, Cord/0000-0001-9773-522X; Ostrander,
Elaine/0000-0001-6075-9738
FU NSF; Biowulf Linux cluster at the National Institutes of Health;
Intramural Program of the National Human Genome Research Institute;
Intramural Program of the National Cancer Institute; National Institutes
of Health Cambridge Scholars Program; National Cancer Institute
[UC2CA148149]
FX We thank the dog owners for donating blood samples to research. We thank
Adam Boyko for additional information about published canid genomes. We
also thank the National Intramural Sequencing Program, the Next
Generation Sequencing Platform of the University of Bern, Wayne Pfeiffer
at the San Diego Supercomputer Center with support from NSF, and the
Biowulf Linux cluster at the National Institutes of Health. This work
was supported by the Intramural Program of the National Human Genome
Research Institute (E.A.O., B.D., B.W.D., M.R., E.K., D.M.K., H.G.P.,
E.S.C.), the Intramural Program of the National Cancer Institute
(A.H.L.), the National Institutes of Health Cambridge Scholars Program
(B.D.), and UC2CA148149 from the National Cancer Institute (M.J.H.,
J.M.T., R.R., J.J.C., awarded to J.M.T.). The funders had no role in
study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 47
TC 9
Z9 9
U1 1
U2 8
PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
PI COLD SPRING HARBOR
PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA
SN 1088-9051
EI 1549-5469
J9 GENOME RES
JI Genome Res.
PD NOV
PY 2015
VL 25
IS 11
BP 1646
EP 1655
DI 10.1101/gr.190314.115
PG 10
WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Genetics & Heredity
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Genetics & Heredity
GA CV6BL
UT WOS:000364355600006
PM 26232412
ER
PT J
AU Resnik, DB
AF Resnik, David B.
TI The Censor's Hand: The Misregulation of Human-Subject Research
SO HASTINGS CENTER REPORT
LA English
DT Book Review
AB Very few people who read Carl Schneider's The Censor's Hand: The Misregulation of Human-Subject Research (MIT Press, 2015) will have a neutral opinion of his book. Schneider defends the radical thesis that the system of regulating human subjects research is not just broken but deeply misguided and therefore needs to be abolished. While some researchers who are frustrated with the current regime will welcome Schneider's scathing critiques of institutional review boards and the regulations they enforce, those who view the status quo as a necessary, though perhaps flawed, means of protecting human subjects will recoil from his arguments and conclusions. Schneider rejects reform efforts, such as the proposed revisions to the Common Rule, as likely to be short-lived and ineffective. He argues that professional self-regulation and tort law can do a better job of protecting human subjects and advancing research than government regulation.
C1 [Resnik, David B.] Natl Inst Environm Hlth Sci, Inst Review Board, Res Triangle Pk, NC 27709 USA.
RP Resnik, DB (reprint author), Natl Inst Environm Hlth Sci, Inst Review Board, Res Triangle Pk, NC 27709 USA.
FU National Institute for Environmental Health Sciences at the National
Institutes of Health
FX This research was supported by the intramural program of the National
Institute for Environmental Health Sciences at the National Institutes
of Health. It does not represent the views of the NIEHS, NIH, or U.S.
government.
NR 1
TC 1
Z9 1
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0093-0334
EI 1552-146X
J9 HASTINGS CENT REP
JI Hastings Cent. Rep.
PD NOV-DEC
PY 2015
VL 45
IS 6
BP 49
EP 50
DI 10.1002/hast.517
PG 2
WC Ethics; Health Care Sciences & Services; Medical Ethics; Social
Sciences, Biomedical
SC Social Sciences - Other Topics; Health Care Sciences & Services; Medical
Ethics; Biomedical Social Sciences
GA CW1YD
UT WOS:000364787000015
PM 26556146
ER
PT J
AU Arem, H
Matthews, CE
Lee, IM
AF Arem, Hannah
Matthews, Charles E.
Lee, I-Min
TI Physical Activity and Successful Aging: Even a Little Is Good Reply
SO JAMA Internal Medicine
LA English
DT Letter
C1 [Arem, Hannah; Matthews, Charles E.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Lee, I-Min] Harvard Univ, Sch Med, Boston, MA USA.
RP Arem, H (reprint author), NCI, Div Canc Epidemiol & Genet, 9609 Med Ctr Dr,Rm 6E314,MSC 9768, Bethesda, MD 20892 USA.
EM Aremhe2@mail.nih.gov
NR 3
TC 1
Z9 1
U1 2
U2 4
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 NOV
PY 2015
VL 175
IS 11
BP 1863
EP 1863
DI 10.1001/jamainternmed.2015.4750
PG 1
WC Medicine, General & Internal
SC General & Internal Medicine
GA CV7BO
UT WOS:000364427200037
PM 26524743
ER
PT J
AU Hingson, R
Zha, WX
White, A
Simons-Morton, B
AF Hingson, Ralph
Zha, Wenxing
White, Aaron
Simons-Morton, Bruce
TI Screening and Brief Alcohol Counseling of College Students and Persons
Not in School
SO JAMA Pediatrics
LA English
DT Letter
ID INTERVENTIONS; ADOLESCENTS
C1 [Hingson, Ralph; Zha, Wenxing] NIAAA, Div Epidemiol & Prevent Res, Bethesda, MD 20892 USA.
[White, Aaron] NIAAA, Off Director, Bethesda, MD 20892 USA.
[Simons-Morton, Bruce] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, Rockville, MD USA.
RP Hingson, R (reprint author), NIAAA, Div Epidemiol & Prevent Res, 5635 Fishers Ln,Room 2074, Bethesda, MD 20892 USA.
EM rhingson@mail.nih.gov
OI Simons-Morton, Bruce/0000-0003-1099-6617
FU Intramural NIH HHS; NICHD NIH HHS [HHSN267200800009C,
HHSN275201200001I]; PHS HHS [HHSN267200800009C]
NR 6
TC 1
Z9 1
U1 1
U2 1
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 2168-6203
EI 2168-6211
J9 JAMA PEDIATR
JI JAMA Pediatr.
PD NOV
PY 2015
VL 169
IS 11
BP 1068
EP 1070
DI 10.1001/jamapediatrics.2015.2231
PG 4
WC Pediatrics
SC Pediatrics
GA CV7CM
UT WOS:000364430000021
PM 26414397
ER
PT J
AU Bonilla, FA
Khan, DA
Ballas, ZK
Chinen, J
Frank, MM
Hsu, JT
Keller, M
Kobrynski, LJ
Komarow, HD
Mazer, B
Nelson, RP
Orange, JS
Routes, JM
Shearer, WT
Sorensen, RU
Verbsky, JW
Bernstein, DI
Blessing-Moore, J
Lang, D
Nicklas, RA
Oppenheimer, J
Portnoy, JM
Randolph, CR
Schuller, D
Spector, SL
Tilles, S
Wallace, D
AF Bonilla, Francisco A.
Khan, David A.
Ballas, Zuhair K.
Chinen, Javier
Frank, Michael M.
Hsu, Joyce T.
Keller, Michael
Kobrynski, Lisa J.
Komarow, Hirsh D.
Mazer, Bruce
Nelson, Robert P., Jr.
Orange, Jordan S.
Routes, John M.
Shearer, William T.
Sorensen, Ricardo U.
Verbsky, James W.
Bernstein, David I.
Blessing-Moore, Joann
Lang, David
Nicklas, Richard A.
Oppenheimer, John
Portnoy, Jay M.
Randolph, Christopher R.
Schuller, Diane
Spector, Sheldon L.
Tilles, Stephen
Wallace, Dana
TI Practice parameter for the diagnosis and management of primary
immunodeficiency
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Editorial Material
AB The American Academy of Allergy, Asthma & Immunology (AAAAI) and the American College of Allergy, Asthma & Immunology (ACAAI) have jointly accepted responsibility for establishing the "Practice parameter for the diagnosis and management of primary immunodeficiency.'' This is a complete and comprehensive document at the current time. The medical environment is a changing environment, and not all recommendations will be appropriate for all patients. Because this document incorporated the efforts of many participants, no single individual, including those who served on the Joint Task Force, is authorized to provide an official AAAAI or ACAAI interpretation of these practice parameters. Any request for information about or an interpretation of these practice parameters by the AAAAI or ACAAI should be directed to the Executive Offices of the AAAAI, the ACAAI, and the Joint Council of Allergy, Asthma & Immunology. These parameters are not designed for use by pharmaceutical companies in drug promotion.
C1 [Bonilla, Francisco A.] Boston Childrens Hosp, Boston, MA 02115 USA.
[Bonilla, Francisco A.] Harvard Univ, Sch Med, Pediat, Boston, MA USA.
[Khan, David A.] Univ Texas SW Med Ctr Dallas, Internal Med, Dallas, TX 75390 USA.
[Bernstein, David I.] Univ Cincinnati, Coll Med, Div Immunol Allergy & Rheumatol, Clin Med & Environm Hlth, Cincinnati, OH USA.
[Blessing-Moore, Joann] Stanford Univ, Med Ctr, Dept Immunol, Med & Pediat, Palo Alto, CA 94304 USA.
[Lang, David] Cleveland Clin Fdn, Allergy Immunol Sect Resp Inst, Cleveland, OH 44195 USA.
[Lang, David] Cleveland Clin Fdn, Allergy & Immunol Fellowship Training Program, Cleveland, OH 44195 USA.
[Nicklas, Richard A.] George Washington Med Ctr, Med, Washington, DC USA.
[Oppenheimer, John] Univ Med & Dent New Jersey, Pulm & Allergy Associates, Dept Internal Med, Morristown, NJ USA.
[Portnoy, Jay M.] Childrens Mercy Hosp, Sect Allergy Asthma & Immunol, Kansas City, MO 64108 USA.
[Portnoy, Jay M.] Univ Missouri, Kansas City Sch Med, Pediat, Kansas City, MO 64110 USA.
[Randolph, Christopher R.] Yale Affiliated Hosp, Pediat Allergy Immunol, Ctr Allergy Asthma & Immunol, Waterbury, CT USA.
[Schuller, Diane] Penn State Univ, Milton S Hershey Med Coll, Pediat, Hershey, PA USA.
[Schuller, Diane] Penn State Univ, Milton S Hershey Med Coll, Allergy & Immunol, Hershey, PA USA.
[Spector, Sheldon L.] Univ Calif Los Angeles, Sch Med, Med, Los Angeles, CA USA.
[Tilles, Stephen] Univ Washington, Sch Med, Med, Redmond, WA USA.
[Wallace, Dana] Nova SE Univ, Coll Osteopath Med, Med, Davie, FL USA.
[Ballas, Zuhair K.] Univ Iowa, Dept Internal Med, Div Immunol, Iowa City, IA 52242 USA.
[Ballas, Zuhair K.] Iowa City Vet Adm Med Ctr, Iowa City, IA USA.
[Chinen, Javier] Lake Houston Allergy & Immunol, Allergy & Immunol, Humble, TX USA.
[Frank, Michael M.] Duke Univ, Med Ctr, Dept Pediat, Pediat,Childrens Hlth Ctr, Durham, NC 27710 USA.
[Frank, Michael M.] Duke Univ, Med Ctr, Dept Pediat, Immunol & Med,Childrens Hlth Ctr, Durham, NC 27710 USA.
[Hsu, Joyce T.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Rheumatol Allergy & Immunol, Boston, MA 02115 USA.
[Hsu, Joyce T.] Harvard Univ, Sch Med, Pediat, Boston, MA 02115 USA.
[Keller, Michael] Childrens Natl Med Ctr, Pediat, Washington, DC 20010 USA.
[Kobrynski, Lisa J.] Emory Univ, Sch Med, Pediat, Atlanta, GA USA.
[Komarow, Hirsh D.] NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA.
[Mazer, Bruce] McGill Univ, Montreal Childrens Hosp, Hlth Ctr, Allergy & Immunol, Montreal, PQ H3H 1P3, Canada.
[Mazer, Bruce] McGill Univ, Pediat, Montreal, PQ, Canada.
[Nelson, Robert P., Jr.] Indiana Univ Sch Med, Div Hematol & Oncol, Med & Pediat, Indianapolis, IN 46202 USA.
[Nelson, Robert P., Jr.] Indiana Univ Sch Med, Div Stem Cell Transplantat, Med & Pediat, Indianapolis, IN 46202 USA.
[Nelson, Robert P., Jr.] Indiana Univ Sch Med, Riley Hosp, Pediat Immunodeficiency Clin, Indianapolis, IN 46202 USA.
[Nelson, Robert P., Jr.] IU Melvin & Bren Simon Canc Ctr, Indianapolis, IN USA.
[Orange, Jordan S.] Texas Childrens Hosp, Immunol Allergy & Rheumatol, Houston, TX 77030 USA.
[Orange, Jordan S.] Texas Childrens Hosp, Ctr Human Immunobiol, Houston, TX 77030 USA.
[Orange, Jordan S.] Baylor Coll Med, Pathol & Immunol, Houston, TX 77030 USA.
[Orange, Jordan S.] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA.
[Routes, John M.] Med Coll Wisconsin, Allergy & Clin Immunol, Milwaukee, WI 53226 USA.
[Routes, John M.] Med Coll Wisconsin, Pediat & Med, Milwaukee, WI 53226 USA.
[Shearer, William T.] Texas Childrens Hosp, Allergy & Immunol Serv, Houston, TX 77030 USA.
[Shearer, William T.] Baylor Coll Med, Pediat & Immunol, Houston, TX 77030 USA.
[Sorensen, Ricardo U.] Louisiana State Univ, Hlth Sci Ctr, Dept Pediat, New Orleans, LA USA.
[Verbsky, James W.] Med Coll Wisconsin, Pediat & Microbiol & Med Genet, Milwaukee, WI 53226 USA.
RP Bonilla, FA (reprint author), Boston Childrens Hosp, Boston, MA 02115 USA.
EM francisco.bonilla@childrens.harvard.edu
FU Intramural NIH HHS
NR 1
TC 27
Z9 27
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 NOV
PY 2015
VL 136
IS 5
BP 1186
EP 1205
DI 10.1016/j.jaci.2015.04.049
PG 20
WC Allergy; Immunology
SC Allergy; Immunology
GA CW1YE
UT WOS:000364787200006
PM 26371839
ER
PT J
AU Holzinger, D
Fassl, SK
de Jager, W
Lohse, P
Rohrig, UF
Gattorno, M
Omenetti, A
Chiesa, S
Schena, F
Austermann, J
Vogl, T
Kuhns, DB
Holland, SM
Rodriguez-Gallego, C
Lopez-Almaraz, R
Arostegui, JI
Colino, E
Roldan, R
Fessatou, S
Isidor, B
Poignant, S
Ito, K
Epple, HJ
Bernstein, JA
Jeng, M
Frankovich, J
Lionetti, G
Church, JA
Ong, PY
LaPlant, M
Abinun, M
Skinner, R
Bigley, V
Sachs, UJ
Hinze, C
Hoppenreijs, E
Ehrchen, J
Foell, D
Chae, JJ
Ombrello, A
Aksentijevich, I
Sunderkoetter, C
Roth, J
AF Holzinger, Dirk
Fassl, Selina Kathleen
de Jager, Wilco
Lohse, Peter
Roehrig, Ute F.
Gattorno, Marco
Omenetti, Alessia
Chiesa, Sabrina
Schena, Francesca
Austermann, Judith
Vogl, Thomas
Kuhns, Douglas B.
Holland, Steven M.
Rodriguez-Gallego, Carlos
Lopez-Almaraz, Ricardo
Arostegui, Juan I.
Colino, Elena
Roldan, Rosa
Fessatou, Smaragdi
Isidor, Bertrand
Poignant, Sylvaine
Ito, Koichi
Epple, Hans-Joerg
Bernstein, Jonathan A.
Jeng, Michael
Frankovich, Jennifer
Lionetti, Geraldina
Church, Joseph A.
Ong, Peck Y.
LaPlant, Mona
Abinun, Mario
Skinner, Rod
Bigley, Venetia
Sachs, Ulrich J.
Hinze, Claas
Hoppenreijs, Esther
Ehrchen, Jan
Foell, Dirk
Chae, Jae Jin
Ombrello, Amanda
Aksentijevich, Ivona
Sunderkoetter, Cord
Roth, Johannes
TI Single amino acid charge switch defines clinically distinct
proline-serine-threonine phosphatase-interacting protein 1
(PSTPIP1)-associated inflammatory diseases
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Article
DE Hyperzincemia and hypercalprotectinemia; myeloid-related protein 8/14;
calprotectin; S100 proteins; zinc; proline-serine-threonine
phosphatase-interacting protein 1; pyogenic arthritis; pyoderma
gangrenosum, and acne syndrome; genotype; phenotype; autoinflammation
ID JUVENILE IDIOPATHIC ARTHRITIS; PAPA SYNDROME; PYODERMA-GANGRENOSUM;
ZINC-METABOLISM; RECEPTOR 4; PYOGENIC ARTHRITIS; INTERFERON-GAMMA;
GENE-EXPRESSION; IN-VITRO; T-CELLS
AB Background: Hyperzincemia and hypercalprotectinemia (Hz/Hc) is a distinct autoinflammatory entity involving extremely high serum concentrations of the proinflammatory alarmin myeloid-related protein (MRP) 8/14 (S100A8/S100A9 and calprotectin).
Objective: We sought to characterize the genetic cause and clinical spectrum of Hz/Hc.
Methods: Proline-serine-threonine phosphatase-interacting protein 1 (PSTPIP1) gene sequencing was performed in 14 patients with Hz/Hc, and their clinical phenotype was compared with that of 11 patients with pyogenic arthritis, pyoderma gangrenosum, and acne (PAPA) syndrome. PSTPIP1-pyrin interactions were analyzed by means of immunoprecipitation and Western blotting. A structural model of the PSTPIP1 dimer was generated. Cytokine profiles were analyzed by using the multiplex immunoassay, and MRP8/14 serum concentrations were analyzed by using an ELISA.
Results: Thirteen patients were heterozygous for a missense mutation in the PSTPIP1 gene, resulting in a p.E250K mutation, and 1 carried a mutation resulting in p. E257K. Both mutations substantially alter the electrostatic potential of the PSTPIP1 dimer model in a region critical for protein-protein interaction. Patients with Hz/Hc have extremely high MRP8/14 concentrations (2045 +/- 1300 mu g/mL) compared with those with PAPA syndrome (116 +/- 74 mu g/mL) and have a distinct clinical phenotype. A specific cytokine profile is associated with Hz/Hc. Hz/Hc mutations altered protein binding of PSTPIP1, increasing interaction with pyrin through phosphorylation of PSTPIP1.
Conclusion: Mutations resulting in charge reversal in the y-domain of PSTPIP1 (E -> K) and increased interaction with pyrin cause a distinct autoinflammatory disorder defined by clinical and biochemical features not found in patients with PAPA syndrome, indicating a unique genotype-phenotype correlation for mutations in the PSTPIP1 gene. This is the first inborn autoinflammatory syndrome in which inflammation is driven by uncontrolled release of members of the alarmin family.
C1 [Holzinger, Dirk; Fassl, Selina Kathleen; Austermann, Judith; Vogl, Thomas; Roth, Johannes] Univ Munster, Inst Immunol, D-48149 Munster, Germany.
[Holzinger, Dirk; Austermann, Judith; Vogl, Thomas; Hinze, Claas; Ehrchen, Jan; Foell, Dirk; Sunderkoetter, Cord; Roth, Johannes] Univ Munster, Univ Hosp Muenster, Interdisciplinary Ctr Clin Res IZKF, D-48149 Munster, Germany.
[Holzinger, Dirk; Foell, Dirk] Univ Munster, Univ Childrens Hosp Muenster, Dept Paediat Rheumatol & Immunol, D-48149 Munster, Germany.
[de Jager, Wilco; Hinze, Claas] Univ Med Ctr Utrecht, Dept Paediat Immunol, Lab Translat Immunol, Utrecht, Netherlands.
[Lohse, Peter] Univ Munich, Dept Clin Chem Grosshadern, D-81377 Munich, Germany.
[Roehrig, Ute F.] Swiss Inst Bioinformat, Mol Modeling Grp, Lausanne, Switzerland.
[Gattorno, Marco; Omenetti, Alessia; Chiesa, Sabrina; Schena, Francesca] G Gaslini Sci Inst, Div Pediat 2, Genoa, Italy.
[Kuhns, Douglas B.] Leidos Biomed Res, Frederick, MD USA.
[Holland, Steven M.] NIAID, NIH, Bethesda, MD USA.
[Rodriguez-Gallego, Carlos] Hosp Univ Son Espases, Dept Immunol, Palma De Mallorca, Spain.
[Lopez-Almaraz, Ricardo] Hosp Univ Canarias, Dept Pediat, San Cristobal la Laguna, Spain.
[Arostegui, Juan I.] Hosp Clin IDIBAPS, Dept Immunol CDB, Barcelona, Spain.
[Colino, Elena] Complejo Hosp Univ Insular Materno Infant, Dept Paediat, Las Palmas Gran Canaria, Spain.
[Roldan, Rosa] Hosp Univ Reina Sofia, Dept Pediat Rheumatol, Cordoba, Spain.
[Fessatou, Smaragdi] Univ Athens, Sch Med, ATTIKON Hosp, Dept Pediat 3, GR-10679 Athens, Greece.
[Isidor, Bertrand] Ctr Hosp Univ, Serv Genet Med, Nantes, France.
[Poignant, Sylvaine] CH Cholet, Serv Pediat, Cholet, France.
[Ito, Koichi] Nagoya City Univ, Grad Sch Med Sci, Dept Pediat & Neonatol, Nagoya, Aichi, Japan.
[Epple, Hans-Joerg] Charite, Dept Gastroenterol Infect Dis & Rheumatol, D-13353 Berlin, Germany.
[Bernstein, Jonathan A.; Jeng, Michael; Frankovich, Jennifer] Stanford Univ, Sch Med, Dept Pediat, Stanford, CA 94305 USA.
[Lionetti, Geraldina] Univ Calif San Francisco, Dept Pediat, San Francisco, CA USA.
[Church, Joseph A.; Ong, Peck Y.] Univ So Calif, Keck Sch Med, Div Clin Immunol & Allergy, Childrens Hosp Los Angeles, Los Angeles, CA 90033 USA.
[Church, Joseph A.; Ong, Peck Y.] Univ So Calif, Keck Sch Med, Dept Pediat, Los Angeles, CA 90033 USA.
[LaPlant, Mona] Childrens Hosp & Clin Minnesota, St Paul, MN USA.
[Abinun, Mario] Great North Childrens Hosp, Dept Paediat Immunol, Newcastle Upon Tyne, Tyne & Wear, England.
[Abinun, Mario] Great North Childrens Hosp, Childrens BMT Unit, Newcastle Upon Tyne, Tyne & Wear, England.
[Abinun, Mario] Newcastle Univ, Inst Clin Med, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England.
[Skinner, Rod] Royal Victoria Infirm, Great North Childrens Hosp, Dept Paediat & Adolescent Haematol & Oncol, Newcastle Upon Tyne NE1 4LP, Tyne & Wear, England.
[Skinner, Rod] Royal Victoria Infirm, Great North Childrens Hosp, Childrens BMT Unit, Newcastle Upon Tyne NE1 4LP, Tyne & Wear, England.
[Skinner, Rod] Newcastle Univ, Northern Inst Canc Res, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England.
[Bigley, Venetia] Newcastle Univ, Sch Med, Human Dendrit Cell Lab, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England.
[Sachs, Ulrich J.] Univ Giessen, Inst Clin Immunol & Transfus Med, Giessen, Germany.
[Hinze, Claas] Deutsch Zentrum Kinder & Jugendrheumatol, Garmisch Partenkirchen, Germany.
[Hoppenreijs, Esther] St Maartens Clin, Dept Paediat Paediat Rheumatol, Nijmegen, Netherlands.
[Hoppenreijs, Esther] Radboud Univ Nijmegen, Ctr Med, NL-6525 ED Nijmegen, Netherlands.
[Ehrchen, Jan; Sunderkoetter, Cord] Univ Hosp Muenster, Dept Dermatol, Munster, Germany.
[Chae, Jae Jin; Ombrello, Amanda; Aksentijevich, Ivona] NHGRI, NIH, Bethesda, MD 20892 USA.
[Ehrchen, Jan; Sunderkoetter, Cord] Univ Hosp Muenster, Dept Translat Dermatoinfectiol, Munster, Germany.
RP Roth, J (reprint author), Univ Munster, Inst Immunol, D-48149 Munster, Germany.
EM rothj@uni-muenster.de
RI Omenetti, Alessia/K-5975-2016;
OI Omenetti, Alessia/0000-0002-8220-0385; Fassl,
Selina/0000-0002-6356-5012; Arostegui, Juan Ignacio/0000-0003-4757-504X;
Hinze, Claas/0000-0001-9247-4729; Roehrig, Ute/0000-0002-4676-4087
FU Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, National Instituters of Health, Department of
Health and Haman Services; National Cancer Institute, National
Institutes of Health [HHSN261200800001E]; "Fondo de Investigaciones
Sanitarias,'' Ministerio de Economia y Competitividad [PI06/1031,
PI10/01718]; European Regional Development Fund European Social Fund
FEDER-FSE; Interdisciplinary Centre for Clinical Research University of
Munster; German Research Foundation [SFB1009]; Bundesministerium fur
Bildung und Forschung (AID-NET) [01GM08100]
FX Supported in part by the Division of Intramural Research, National
Institute of Allergy and Infectious Diseases, National Instituters of
Health, Department of Health and Haman Services (to S.M.H.) and in part
with federal funds from the National Cancer Institute, National
Institutes of Health, under contract no. HHSN261200800001E. The content
of this publication does not necessarily reflect the views or policies
of the Department of Health and Human Services, nor does mention of
trade names, commercial products, or organizations imply endorsement by
the US Government. Also supported by "Fondo de Investigaciones
Sanitarias,'' Ministerio de Economia y Competitividad (PI06/1031,
PI10/01718), with the funding of European Regional Development Fund
European Social Fund FEDER-FSE, the Interdisciplinary Centre for
Clinical Research University of Munster, the German Research Foundation
(SFB1009), and the Bundesministerium fur Bildung und Forschung (AID-NET,
project 01GM08100).
NR 54
TC 5
Z9 5
U1 1
U2 11
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 NOV
PY 2015
VL 136
IS 5
BP 1337
EP 1345
DI 10.1016/j.jaci.2015.04.016
PG 9
WC Allergy; Immunology
SC Allergy; Immunology
GA CW1YE
UT WOS:000364787200024
PM 26025129
ER
PT J
AU Mueller, GA
Pedersen, LC
Glesner, J
Edwards, LL
Zakzuk, J
London, RE
Arruda, LK
Chapman, MD
Caraballo, L
Pomes, A
AF Mueller, Geoffrey A.
Pedersen, Lars C.
Glesner, Jill
Edwards, Lori L.
Zakzuk, Josefina
London, Robert E.
Arruda, L. Karla
Chapman, Martin D.
Caraballo, Luis
Pomes, Anna
TI Analysis of glutathione S-transferase allergen cross-reactivity in a
North American population: Relevance for molecular diagnosis
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Article
DE Cockroach; house dust mite; helminth; glutathione S-transferases (GST);
cross-reactivity; diagnosis
ID HOUSE-DUST-MITE; IGE ANTIBODY-RESPONSES; GERMAN-COCKROACH;
DERMATOPHAGOIDES-PTERONYSSINUS; ASCARIS-LUMBRICOIDES; BLOMIA-TROPICALIS;
ASTHMA; IDENTIFICATION; SENSITIZATION; EXPOSURE
AB Background: It is not clear whether cross-reactivity or cosensitization to glutathione S-transferases (GSTs) occurs in tropical and subtropical environments. In the United States, Bla g 5 is the most important GST allergen and lack of coexposure to GSTs from certain species allows a better assessment of cross-reactivity.
Objectives: To examine the molecular structure of GST allergens from cockroach (Bla g 5), dust mites (Der p 8 and Blo t 8), and helminth (Asc s 13) for potential cross-reactive sites, and to assess the IgE cross-reactivity of sensitized patients from a temperate climate for these allergens for molecular diagnostic purposes.
Methods: Four crystal structures were determined. Sera from patients allergic to cockroach and mite were tested for IgE reactivity to these GSTs. A panel of 6 murine anti-Bla g 5 mAb was assessed for cross-reactivity with the other 3 GSTs using antibody binding assays.
Results: Comparisons of the allergen structures, formed by 2-domain monomers that dimerize, revealed few contiguous regions of similar exposed residues, rendering cross-reactivity unlikely. Accordingly, anti-Bla g 5 or anti-Der p 8 IgE from North American patients did not recognize Der p 8 or Bla g 5, respectively, and neither showed binding to Blo t 8 or Asc s 13. A weaker binding of anti-Bla g 5 IgE to Der p 8 versus Bla g 5 (similar to 100-fold) was observed by inhibition assays, similar to a weak recognition of Der p 8 by anti-Bla g 5 mAb. Patients from tropical Colombia had IgE to all 4 GSTs.
Conclusions: The lack of significant IgE cross-reactivity among the 4 GSTs is in agreement with the low shared amino acid identity at the molecular surface. Each GST is needed for accurate molecular diagnosis in different geographic areas.
C1 [Mueller, Geoffrey A.; Pedersen, Lars C.; Edwards, Lori L.; London, Robert E.] NIEHS, Genome Integr & Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA.
[Glesner, Jill; Chapman, Martin D.; Pomes, Anna] Indoor Biotechnol Inc, Charlottesville, VA 22903 USA.
[Zakzuk, Josefina; Caraballo, Luis] Univ Cartagena, Inst Immunol Res, Cartagena, Colombia.
[Zakzuk, Josefina; Caraballo, Luis] Fdn Dev Med & Biol Sci, Cartagena, Colombia.
[Arruda, L. Karla] Univ Sao Paulo, Ribeirao Preto Med Sch, Sao Paulo, Brazil.
RP Pomes, A (reprint author), Indoor Biotechnol Inc, 1216 Harris St, Charlottesville, VA 22903 USA.
EM apomes@inbio.com
RI Arruda, L. Karla /D-5845-2013;
OI Arruda, L. Karla /0000-0002-7505-210X; Pomes, Anna/0000-0002-8729-1829
FU National Institute of Environmental Health Sciences, National Institutes
of Health [Z01- ES102885-01, ZIA- ES102645]; National Institute of
Allergy and Infectious Diseases of the National Institutes of Health
[R01AI077653]; US Department of Energy, Office of Science, Office of
Basic Energy Sciences [W-31-109-Eng-38]; Administrative Department of
Science, Technology and Innovation (Colciencias) (Colombia) [406-2011,
201-2015]
FX This study was supported in part by the Intramural Research Program of
the National Institute of Environmental Health Sciences, National
Institutes of Health (Research Project nos. Z01- ES102885-01 to R.E.L.
and ZIA- ES102645 to L.C.P.), and in part by the National Institute of
Allergy and Infectious Diseases of the National Institutes of Health
(under Award no. R01AI077653 to A.P. and M.D.C.). Use of the Advance
Photon Source was supported by the US Department of Energy, Office of
Science, Office of Basic Energy Sciences (contract no. W-31-109-Eng-38).
The content is solely the responsibility of the authors and does not
necessarily represent the official views of the National Institutes of
Health. Research was also supported by the Administrative Department of
Science, Technology and Innovation (Colciencias) Contract 406-2011 and
201-2015 (Colombia).
NR 37
TC 5
Z9 5
U1 1
U2 4
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 NOV
PY 2015
VL 136
IS 5
BP 1369
EP 1377
DI 10.1016/j.jaci.2015.03.015
PG 9
WC Allergy; Immunology
SC Allergy; Immunology
GA CW1YE
UT WOS:000364787200027
PM 25930195
ER
PT J
AU Fernandez-Boyanapalli, RF
Falcone, EL
Zerbe, CS
Marciano, BE
Frasch, SC
Henson, PM
Holland, SM
Bratton, DL
AF Fernandez-Boyanapalli, Ruby F.
Falcone, Emilia Liana
Zerbe, Christa S.
Marciano, Beatriz E.
Frasch, S. Courtney
Henson, Peter M.
Holland, Steven M.
Bratton, Donna L.
TI Impaired efferocytosis in human chronic granulomatous disease is
reversed by pioglitazone treatment
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Letter
ID STERILE INFLAMMATION; MACROPHAGE; CGD
C1 [Fernandez-Boyanapalli, Ruby F.; Frasch, S. Courtney; Henson, Peter M.; Bratton, Donna L.] Natl Jewish Hlth, Dept Pediat, Denver, CO 80206 USA.
[Falcone, Emilia Liana; Zerbe, Christa S.; Marciano, Beatriz E.; Holland, Steven M.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
RP Fernandez-Boyanapalli, RF (reprint author), Natl Jewish Hlth, Dept Pediat, Denver, CO 80206 USA.
EM brattond@njhealth.org
FU Intramural NIH HHS; NHLBI NIH HHS [R01 HL114381, HL114381, P01
HL034303]; NIAID NIH HHS [AI058228, R01 AI110408, AI110408, R01
AI058228, R56 AI058228]
NR 10
TC 2
Z9 2
U1 0
U2 1
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
EI 1097-6825
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD NOV
PY 2015
VL 136
IS 5
BP 1399
EP 1401
DI 10.1016/j.jaci.2015.07.034
PG 4
WC Allergy; Immunology
SC Allergy; Immunology
GA CW1YE
UT WOS:000364787200031
PM 26386811
ER
PT J
AU Crestani, E
Volpi, S
Candotti, F
Giliani, S
Notarangelo, LD
Chu, J
Becerra, JCA
Buchbinder, D
Chou, J
Geha, RS
Kanariou, M
King, A
Mazza, C
Moratto, D
Sokolic, R
Garabedian, E
Porta, F
Putti, MC
Wakim, RH
Tsitsikov, E
Pai, SY
Notarangelo, LD
AF Crestani, Elena
Volpi, Stefano
Candotti, Fabio
Giliani, Silvia
Notarangelo, Lucia Dora
Chu, Julia
Becerra, Juan Carlos Aldave
Buchbinder, David
Chou, Janet
Geha, Raif S.
Kanariou, Maria
King, Alejandra
Mazza, Cinzia
Moratto, Daniele
Sokolic, Robert
Garabedian, Elizabeth
Porta, Fulvio
Putti, Maria Caterina
Wakim, Rima H.
Tsitsikov, Erdyni
Pai, Sung-Yun
Notarangelo, Luigi D.
TI Broad spectrum of autoantibodies in patients with Wiskott-Aldrich
syndrome and X-linked thrombocytopenia
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Letter
ID SYNDROME PROTEIN-DEFICIENCY; AUTOIMMUNITY; HUMANS; CELLS
C1 [Crestani, Elena; Volpi, Stefano; Chou, Janet; Geha, Raif S.; Notarangelo, Luigi D.] Boston Childrens Hosp, Div Immunol, Boston, MA 02115 USA.
[Chu, Julia; Pai, Sung-Yun] Boston Childrens Hosp, Div Hematol Oncol, Boston, MA USA.
[Tsitsikov, Erdyni] Boston Childrens Hosp, Dept Lab Med, Boston, MA USA.
[Volpi, Stefano] Univ Genoa, Dept Neurosci Rehabil Ophthalmol Genet Maternal &, Genoa, Italy.
[Candotti, Fabio; Sokolic, Robert; Garabedian, Elizabeth] NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA.
[Giliani, Silvia; Mazza, Cinzia; Moratto, Daniele] Univ Brescia, Angelo Nocivelli Inst Mol Med, Brescia, Italy.
[Notarangelo, Lucia Dora; Porta, Fulvio] Spedali Civil Brescia, Pediat Hematol Oncol Unit, I-25125 Brescia, Italy.
[Becerra, Juan Carlos Aldave] Rebagliati Martins Natl Hosp, Div Allergy & Clin Immunol, Lima, Peru.
[Buchbinder, David] Univ Calif Irvine, Childrens Hosp Orange Cty, Div Pediat Hematol, Irvine, CA USA.
[Kanariou, Maria] Aghia Sophia Childrens Hosp, Dept Immunol, Athens, Greece.
[King, Alejandra] Hosp Ninos Luis Calvo Mackenna, Div Pediat Immunol, Santiago, Chile.
[Putti, Maria Caterina] Univ Hosp, Dept Woman & Child Hlth, Clin Pediat Hematol Oncol, Padua, Italy.
[Wakim, Rima H.] Amer Univ Beirut, Dept Pediat & Adolescent Med, Beirut, Lebanon.
RP Crestani, E (reprint author), Boston Childrens Hosp, Div Immunol, Boston, MA 02115 USA.
EM luigi.notarangelo@childrens.harvard.edu
RI Notarangelo, Luigi/F-9718-2016;
OI Notarangelo, Luigi/0000-0002-8335-0262; Candotti,
Fabio/0000-0001-6399-6042
FU NHLBI NIH HHS [5P01HL059561-13, 5T32HL007574-33, P01 HL059561]; NIAID
NIH HHS [5T32AI007512, T32 AI007512]
NR 12
TC 3
Z9 4
U1 3
U2 7
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 NOV
PY 2015
VL 136
IS 5
BP 1401
EP 1404
DI 10.1016/j.jaci.2015.08.010
PG 8
WC Allergy; Immunology
SC Allergy; Immunology
GA CW1YE
UT WOS:000364787200032
PM 26409660
ER
PT J
AU Odio, CD
Milligan, KL
McGowan, K
Spergel, AKR
Bishop, R
Boris, L
Urban, A
Welch, P
Heller, T
Kleiner, D
Jackson, MA
Holland, SM
Freeman, AF
AF Odio, Camila D.
Milligan, Ki Lee
McGowan, Katherine
Spergel, Amanda K. Rudman
Bishop, Rachel
Boris, Lisa
Urban, Amanda
Welch, Pamela
Heller, Theo
Kleiner, David
Jackson, Mary Anne
Holland, Steven M.
Freeman, Alexandra F.
TI Endemic mycoses in patients with STAT3-mutated hyper-IgE (Job) syndrome
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Letter
ID INHALED CORTICOSTEROIDS; ASTHMA; ADHERENCE
C1 [Odio, Camila D.; Milligan, Ki Lee; McGowan, Katherine; Spergel, Amanda K. Rudman; Holland, Steven M.; Freeman, Alexandra F.] NIAID, NIH, Bethesda, MD 20892 USA.
[Bishop, Rachel] NEI, NIH, Bethesda, MD 20892 USA.
[Boris, Lisa; Urban, Amanda; Welch, Pamela] Leidos Biomed Res Inc, Clin Monitoring Res Program, Clin Res Directorate, Bethesda, MD USA.
[Heller, Theo] NIDDK, NIH, Bethesda, MD 20892 USA.
[Kleiner, David] NCI, NIH, Bethesda, MD 20892 USA.
[Jackson, Mary Anne] Childrens Mercy Hosp, Bethesda, MD USA.
RP Odio, CD (reprint author), NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM freemaal@mail.nih.gov
OI McGowan, Katherine/0000-0002-4128-5722; Kleiner,
David/0000-0003-3442-4453
FU CCR NIH HHS [HHSN261200800001C]; Howard Hughes Medical Institute;
Intramural NIH HHS [Z99 AI999999]; NCI NIH HHS [HHSN261200800001E]; PHS
HHS [HHSN261200800001E]
NR 13
TC 4
Z9 5
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 NOV
PY 2015
VL 136
IS 5
BP 1411
EP 1413
DI 10.1016/j.jaci.2015.07.003
PG 10
WC Allergy; Immunology
SC Allergy; Immunology
GA CW1YE
UT WOS:000364787200036
PM 26292779
ER
PT J
AU Hox, V
Metcalfe, DD
Olivera, A
AF Hox, Valerie
Metcalfe, Dean D.
Olivera, Ana
TI Impact of sex on anaphylaxis severity-data from the Anaphylaxis Registry
Reply
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Letter
ID MENOPAUSE
C1 [Hox, Valerie; Metcalfe, Dean D.; Olivera, Ana] NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA.
RP Hox, V (reprint author), NIAID, Lab Allerg Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM Ana.Olivera@nih.gov
FU Intramural NIH HHS
NR 7
TC 0
Z9 0
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
EI 1097-6825
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD NOV
PY 2015
VL 136
IS 5
BP 1426
EP 1426
DI 10.1016/j.jaci.2015.08.002
PG 1
WC Allergy; Immunology
SC Allergy; Immunology
GA CW1YE
UT WOS:000364787200043
PM 26392053
ER
PT J
AU Bonilla, FA
Khan, DA
Ballas, ZK
Chinen, J
Frank, MM
Hsu, JT
Keller, M
Kobrynski, LJ
Komarow, HD
Mazer, B
Nelson, RP
Orange, JS
Routes, JM
Shearer, WT
Sorensen, RU
Verbsky, JW
Bernstein, DI
Blessing-Moore, J
Lang, D
Nicklas, RA
Oppenheimer, J
Portnoy, JM
Randolph, CR
Schuller, D
Spector, SL
Tilles, S
Wallace, D
AF Bonilla, Francisco A.
Khan, David A.
Ballas, Zuhair K.
Chinen, Javier
Frank, Michael M.
Hsu, Joyce T.
Keller, Michael
Kobrynski, Lisa J.
Komarow, Hirsh D.
Mazer, Bruce
Nelson, Robert P., Jr.
Orange, Jordan S.
Routes, John M.
Shearer, William T.
Sorensen, Ricardo U.
Verbsky, James W.
Bernstein, David I.
Blessing-Moore, Joann
Lang, David
Nicklas, Richard A.
Oppenheimer, John
Portnoy, Jay M.
Randolph, Christopher R.
Schuller, Diane
Spector, Sheldon L.
Tilles, Stephen
Wallace, Dana
TI Practice parameter for the diagnosis and management of primary
immunodeficiency
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Editorial Material
ID COMMON-VARIABLE-IMMUNODEFICIENCY; CHRONIC GRANULOMATOUS-DISEASE;
STEM-CELL TRANSPLANTATION; HYPER-IGE SYNDROME; X-LINKED
AGAMMAGLOBULINEMIA; WISKOTT-ALDRICH-SYNDROME; PULMONARY ALVEOLAR
PROTEINOSIS; BONE-MARROW-TRANSPLANTATION; CHRONIC MUCOCUTANEOUS
CANDIDIASIS; HEMOLYTIC-UREMIC SYNDROME
AB The American Academy of Allergy, Asthma & Immunology (AAAAI) and the American College of Allergy, Asthma & Immunology (ACAAI) have jointly accepted responsibility for establishing the "Practice parameter for the diagnosis and management of primary immunodeficiency.'' This is a complete and comprehensive document at the current time. The medical environment is a changing environment, and not all recommendations will be appropriate for all patients. Because this document incorporated the efforts of many participants, no single individual, including those who served on the Joint Task Force, is authorized to provide an official AAAAI or ACAAI interpretation of these practice parameters. Any request for information about or an interpretation of these practice parameters by the AAAAI or ACAAI should be directed to the Executive Offices of the AAAAI, the ACAAI, and the Joint Council of Allergy, Asthma & Immunology. These parameters are not designed for use by pharmaceutical companies in drug promotion.
C1 [Bonilla, Francisco A.] Boston Childrens Hosp, Boston, MA 02115 USA.
[Bonilla, Francisco A.] Harvard Univ, Sch Med, Pediat, Boston, MA USA.
[Khan, David A.] Univ Texas SW Med Ctr Dallas, Internal Med, Dallas, TX 75390 USA.
[Bernstein, David I.] Univ Cincinnati, Coll Med, Div Immunol Allergy & Rheumatol, Clin Med & Environm Hlth, Cincinnati, OH USA.
[Blessing-Moore, Joann] Stanford Univ, Med Ctr, Dept Immunol, Med & Pediat, Palo Alto, CA 94304 USA.
[Lang, David] Cleveland Clin Fdn, Allergy Immunol Sect, Resp Inst, Cleveland, OH 44195 USA.
[Lang, David] Cleveland Clin Fdn, Allergy & Immunol Fellowship Training Program, Cleveland, OH 44195 USA.
[Nicklas, Richard A.] George Washington Med Ctr, Med, Washington, DC USA.
[Oppenheimer, John] Univ Med & Dent New Jersey, Pulm & Allergy Associates, Dept Internal Med, Morristown, NJ USA.
[Portnoy, Jay M.] Childrens Mercy Hosp, Sect Allergy Asthma & Immunol, Kansas City, MO 64108 USA.
[Portnoy, Jay M.] Univ Missouri, Kansas City Sch Med, Pediat, Kansas City, MO 64110 USA.
[Randolph, Christopher R.] Yale Affiliated Hosp, Pediat Allergy Immunol, Ctr Allergy Asthma & Immunol, Waterbury, CT USA.
[Schuller, Diane] Penn State Univ, Milton S Hershey Med Coll, Pediat, Hershey, PA USA.
[Schuller, Diane] Penn State Univ, Milton S Hershey Med Coll, Allergy & Immunol, Hershey, PA USA.
[Spector, Sheldon L.] Univ Calif Los Angeles, Sch Med, Med, Los Angeles, CA USA.
[Tilles, Stephen] Univ Washington, Sch Med, Med, Redmond, WA USA.
[Wallace, Dana] Nova SE Univ, Coll Osteopath Med, Med, Davie, FL USA.
[Ballas, Zuhair K.] Univ Iowa, Dept Internal Med, Div Immunol, Iowa City, IA 52242 USA.
[Ballas, Zuhair K.] Iowa City Vet Adm Med Ctr, Iowa City, IA USA.
[Chinen, Javier] Lake Houston Allergy & Immunol, Allergy & Immunol, Humble, TX USA.
[Frank, Michael M.] Duke Univ, Med Ctr, Pediat, Durham, NC USA.
[Frank, Michael M.] Duke Univ, Med Ctr, Dept Pediat, Immunol & Med, Durham, NC 27710 USA.
[Hsu, Joyce T.] Harvard Univ, Brigham & Womens Hosp, Div Rheumatol Allergy & Immunol, Sch Med, Boston, MA 02115 USA.
[Hsu, Joyce T.] Harvard Univ, Sch Med, Pediat, Boston, MA USA.
[Keller, Michael] Childrens Natl Med Ctr, Pediat, Washington, DC 20010 USA.
[Kobrynski, Lisa J.] Emory Univ, Sch Med, Atlanta, GA USA.
[Komarow, Hirsh D.] NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA.
[Mazer, Bruce] McGill Univ, Montreal Childrens Hosp, Hlth Ctr, Allergy & Immunol, Montreal, PQ H3H 1P3, Canada.
[Mazer, Bruce] McGill Univ, Pediat, Montreal, PQ, Canada.
[Nelson, Robert P., Jr.] Indiana Univ Sch Med, Div Hematol & Oncol, Med & Pediat, Indianapolis, IN 46202 USA.
[Nelson, Robert P., Jr.] Indiana Univ Sch Med, Div Stem Cell Transplantat, Med & Pediat, Indianapolis, IN 46202 USA.
[Nelson, Robert P., Jr.] Indiana Univ Sch Med, Riley Hosp, Pediat Immunodeficiency Clin, Indianapolis, IN 46202 USA.
[Nelson, Robert P., Jr.] IU Melvin & Bren Simon Canc Ctr, Indianapolis, IN USA.
[Orange, Jordan S.] Texas Childrens Hosp, Immunol Allergy & Rheumatol, Houston, TX 77030 USA.
[Orange, Jordan S.] Texas Childrens Hosp, Ctr Human Immunobiol, Houston, TX 77030 USA.
[Orange, Jordan S.] Baylor Coll Med, Pediat Pathol & Immunol, Houston, TX 77030 USA.
[Orange, Jordan S.] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA.
[Routes, John M.] Med Coll Wisconsin, Allergy & Clin Immunol, Milwaukee, WI 53226 USA.
[Routes, John M.] Med Coll Wisconsin, Pediat & Med, Milwaukee, WI 53226 USA.
[Shearer, William T.] Texas Childrens Hosp, Allergy & Immunol Serv, Houston, TX 77030 USA.
[Shearer, William T.] Baylor Coll Med, Pediat & Immunol, Houston, TX 77030 USA.
[Sorensen, Ricardo U.] Louisiana State Univ, Hlth Sci Ctr, Dept Pediat, New Orleans, LA USA.
[Verbsky, James W.] Med Coll Wisconsin, Pediat & Microbiol & Med Genet, Milwaukee, WI 53226 USA.
RP Bonilla, FA (reprint author), Boston Childrens Hosp, Boston, MA 02115 USA.
EM francisco.bonilla@childrens.harvard.edu
NR 770
TC 0
Z9 0
U1 1
U2 9
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
EI 1097-6825
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD NOV
PY 2015
VL 136
IS 5
PG 78
WC Allergy; Immunology
SC Allergy; Immunology
GA CW1YE
UT WOS:000364787200007
ER
PT J
AU Ekman, C
Elgzyri, T
Strom, K
Almgren, P
Parikh, H
Nitert, MD
Ronn, T
Koivula, FM
Ling, C
Tornberg, AB
Wollmer, P
Eriksson, KF
Groop, L
Hansson, O
AF Ekman, C.
Elgzyri, T.
Strom, K.
Almgren, P.
Parikh, H.
Nitert, Marloes Dekker
Ronn, T.
Koivula, Fiona Manderson
Ling, C.
Tornberg, A. B.
Wollmer, P.
Eriksson, K. F.
Groop, L.
Hansson, O.
TI Less pronounced response to exercise in healthy relatives to type 2
diabetic subjects compared with controls
SO JOURNAL OF APPLIED PHYSIOLOGY
LA English
DT Article
DE type 2 diabetes; exercise intervention; expression analysis; genetic
predisposition; muscle
ID HUMAN SKELETAL-MUSCLE; 1ST-DEGREE RELATIVES; PHYSICAL-ACTIVITY;
FOLLOW-UP; OXIDATIVE-PHOSPHORYLATION; INSULIN-RESISTANCE; AEROBIC
CAPACITY; FAMILY-HISTORY; LIPID-CONTENT; WEIGHT-LOSS
AB Healthy first-degree relatives with heredity of type 2 diabetes (FH+) are known to have metabolic inflexibility compared with subjects without heredity for diabetes (FH-). In this study, we aimed to test the hypothesis that FH+ individuals have an impaired response to exercise compared with FH-. Sixteen FH+ and 19 FH- insulin-sensitive men similar in age, peak oxygen consumption ((V) over dot(O2 peak)), and body mass index completed an exercise intervention with heart rate monitored during exercise for 7 mo. Before and after the exercise intervention, the participants underwent a physical examination and tests for glucose tolerance and exercise capacity, and muscle biopsies were taken for expression analysis. The participants attended, on average, 39 training sessions during the intervention and spent 18.8 MJ on exercise. (V) over dot(O2 peak)/kg increased by 14%, and the participants lost 1.2 kg of weight and 3 cm waist circumference. Given that the FH- group expended 61% more energy during the intervention, we used regression analysis to analyze the response in the FH+ and FH- groups separately. Exercise volume had a significant effect on (V) over dot(O2 peak), weight, and waist circumference in the FH- group, but not in the FH+ group. After exercise, expression of genes involved in metabolism, oxidative phosphorylation, and cellular respiration increased more in the FH- compared with the FH+ group. This suggests that healthy, insulin-sensitive FH+ and FH- participants with similar age, (V) over dot(O2 peak), and body mass index may respond differently to an exercise intervention. The FH+ background might limit muscle adaptation to exercise, which may contribute to the increased susceptibility to type 2 diabetes in FH+ individuals.
C1 [Ekman, C.; Elgzyri, T.; Strom, K.; Almgren, P.; Parikh, H.; Nitert, Marloes Dekker; Ronn, T.; Ling, C.; Eriksson, K. F.; Groop, L.; Hansson, O.] Lund Univ, Malmo Univ Hosp, Clin Res Ctr, Dept Clin Sci, Malmo, Sweden.
[Strom, K.] Mid Sweden Univ, Dept Hlth Sci, Swedish Winter Sports Res Ctr, Ostersund, Sweden.
[Parikh, H.] NCI, Lab Translat Gen, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Koivula, Fiona Manderson; Tornberg, A. B.; Wollmer, P.] Lund Univ, Div Physiotherapy, Dept Hlth Sci, Lund, Sweden.
[Tornberg, A. B.] Lund Univ, Genet Mol Epidemiol Unit, Ctr Diabet, Clin Res Ctr, Malmo, Sweden.
[Wollmer, P.] Lund Univ, Dept Clin Sci, Clin Physiol & Nucl Med Unit, Malmo, Sweden.
RP Hansson, O (reprint author), CRC, SUS, Diabet & Endocrinol, Entrance 72,Bldg 91,Level 12, S-20502 Malmo, Sweden.
EM Ola.Hansson@med.lu.se
RI Ling, Charlotte/Q-2432-2015; Hansson, Ola/F-1793-2011; Dekker Nitert,
Marloes/A-8822-2011
OI Ling, Charlotte/0000-0003-0587-7154; Hansson, Ola/0000-0002-7394-7639;
Dekker Nitert, Marloes/0000-0002-1909-8920
FU Swedish Research Council Linnaeus grant: Lund University Diabetes Centre
[Dnr 349-2006-237]; SFO Exodiab [Dnr 2009-1039]; European Research
Council Advanced Researcher Grant [GA 269045]; NuGo; ALF; Crafoord
Foundation; SV Skanes Diabetes Forening; Wallenberg Foundation; Novo
Nordisk Foundation; EXGENESIS; UMAS Fonder, Magn. Bergvalls Stiftelse;
Syskonen Svenssons Fond; Swedish Diabetes Research Foundation
[2009-060]; European Community
FX This study was supported by the Swedish Research Council Linnaeus grant:
Lund University Diabetes Centre (Dnr 349-2006-237) and SFO Exodiab (Dnr
2009-1039); European Research Council Advanced Researcher Grant (GA
269045); NuGo; ALF; the Crafoord Foundation; SV Skanes Diabetes
Forening; the Wallenberg Foundation; the Novo Nordisk Foundation;
EXGENESIS; UMAS Fonder, Magn. Bergvalls Stiftelse; Syskonen Svenssons
Fond; the Swedish Diabetes Research Foundation (2009-060); and the
European Community's Seventh Framework Programme (FP7/2007-2013).
NR 42
TC 2
Z9 2
U1 3
U2 7
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 8750-7587
EI 1522-1601
J9 J APPL PHYSIOL
JI J. Appl. Physiol.
PD NOV 1
PY 2015
VL 119
IS 9
BP 953
EP 960
DI 10.1152/japplphysiol.01067.2014
PG 8
WC Physiology; Sport Sciences
SC Physiology; Sport Sciences
GA CV7TO
UT WOS:000364478200001
PM 26338460
ER
PT J
AU Zheng, WW
Borgia, A
Borgia, MB
Schuler, B
Best, RB
AF Zheng, Wenwei
Borgia, Alessandro
Borgia, Madeleine B.
Schuler, Benjamin
Best, Robert B.
TI Empirical Optimization of Interactions between Proteins and Chemical
Denaturants in Molecular Simulations
SO JOURNAL OF CHEMICAL THEORY AND COMPUTATION
LA English
DT Article
ID POLARIZABLE FORCE-FIELD; AQUEOUS UREA SOLUTIONS; DER-WAALS INTERACTIONS;
HELIX-COIL TRANSITION; TRP-CAGE MINIPROTEIN; DISORDERED PROTEINS;
FREE-ENERGY; HYDROPHOBIC INTERACTIONS; DISPERSION INTERACTIONS;
GUANIDINIUM CHLORIDE
AB Chemical denaturants are the most commonly used perturbation applied to study protein stability and folding kinetics as well as the properties of unfolded polypeptides. We build on recent work balancing the interactions of proteins and water, and accurate models for the solution properties of urea and guanidinium chloride, to develop a combined force field that is able to capture the strength of interactions between proteins and denaturants. We use solubility data for a model tetraglycine peptide in each denaturant to tune the protein-denaturant interaction by a novel simulation methodology. We validate the results against data for more complex sequences: single-molecule Forster resonance energy transfer data for a 34-residue fragment of the globular protein CspTm and photoinduced electron transfer quenching data for the disordered peptides C(AGQ)(n)W in denaturant solution as well as the chemical denaturation of the mini-protein Trp cage. The combined force field model should aid our understanding of denaturation mechanisms and the interpretation of experiment.
C1 [Zheng, Wenwei; Best, Robert B.] NIH, Natl Inst Diabet & Digest & Kidney Dis, Lab Chem Phys, Bethesda, MD 20892 USA.
[Borgia, Alessandro; Borgia, Madeleine B.; Schuler, Benjamin] Univ Zurich, Dept Biochem, CH-8057 Zurich, Switzerland.
RP Best, RB (reprint author), NIH, Natl Inst Diabet & Digest & Kidney Dis, Lab Chem Phys, Bethesda, MD 20892 USA.
EM robertbe@helix.nih.gov
RI Best, Robert/H-7588-2016; Schuler, Benjamin/E-7342-2011
OI Best, Robert/0000-0002-7893-3543; Schuler, Benjamin/0000-0002-5970-4251
FU Intramural Research Program of National Institute of Diabetes and
Digestive and Kidney Diseases of National Institutes of Health; Swiss
National Science Foundation
FX This work was supported by the Intramural Research Program of the
National Institute of Diabetes and Digestive and Kidney Diseases of the
National Institutes of Health (W.Z. and R.B.B.) and by the Swiss
National Science Foundation (A.B., M.B.B., and B.S.).
NR 70
TC 3
Z9 3
U1 2
U2 4
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1549-9618
EI 1549-9626
J9 J CHEM THEORY COMPUT
JI J. Chem. Theory Comput.
PD NOV
PY 2015
VL 11
IS 11
BP 5543
EP 5553
DI 10.1021/acs.jctc.5b00778
PG 11
WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical
SC Chemistry; Physics
GA CV9NN
UT WOS:000364614000045
PM 26574341
ER
PT J
AU Wang, WX
Corrigan-Cummins, M
Barber, EA
Saleh, LM
Zingone, A
Ghafoor, A
Costello, R
Zhang, Y
Kurlander, RJ
Korde, N
Roccaro, AM
Ghobrial, IM
Landgren, O
Calvo, KR
AF Wang, Weixin
Corrigan-Cummins, Meghan
Barber, Emily A.
Saleh, Layla M.
Zingone, Adriana
Ghafoor, Azam
Costello, Rene
Zhang, Yong
Kurlander, Roger J.
Korde, Neha
Roccaro, Aldo M.
Ghobrial, Irene M.
Landgren, Ola
Calvo, Katherine R.
TI Aberrant Levels of miRNAs in Bone Marrow Microenvironment and Peripheral
Blood of Myeloma Patients and Disease Progression
SO JOURNAL OF MOLECULAR DIAGNOSTICS
LA English
DT Article
ID UNDETERMINED SIGNIFICANCE MGUS; SMOLDERING MULTIPLE-MYELOMA; MONOCLONAL
GAMMOPATHY; MICRORNA EXPRESSION; GENE-EXPRESSION; CIRCULATING MICRORNAS;
14Q32 TRANSLOCATIONS; DOWN-REGULATION; HUMAN LEUKEMIA; PLASMA-CELLS
AB The bone marrow (BM) microenvironment of multiple myeloma (MM) is reported to play a role in the biology of disease. In this study, we found that the extracellular BM microenvironment in MM contains a unique miRNA signature detectable by miRNA microarray and quantitative real-time PCR, which is partially represented in the peripheral blood. Eleven miRNAs were significantly decreased in both BM and serum of MM patients in comparison with controls. Evaluation of these miRNAs in plasma of a separate cohort of MM patients and controls confirmed significantly aberrant Levels of let-7a, let-7b, let-7i, miR-15b, miR-16, and miR-20a in both serum and plasma. We then studied the myeLoma precursor diseases and found that a subset of the MM miRNAs exhibited aberrant expression in monoclonal gammopathy of undetermined significance and smoldering myeLoma. miRNA analysis of enriched CD138(+) plasma cells from MM and monoclonal gammopathy of undetermined significance found that most of the validated MM BM signature miRNAs were significantly decreased in MM plasma cells. Gene expression profiling indicated that multiple targets of the decreased miRNAs found increased expression in MM plasma cells, including ATF2, HRAS, HDAC4, TGFB1, TGFBR1, and mitogen-activated protein kinases. The findings suggest that these miRNAs are detectable in aberrant levels in the peripheral blood of patients with plasma cell proliferation and may play a role in aberrant plasma cell proliferation and disease progression.
C1 [Wang, Weixin; Corrigan-Cummins, Meghan; Barber, Emily A.; Saleh, Layla M.; Ghafoor, Azam; Kurlander, Roger J.; Calvo, Katherine R.] NIH, Hematol Sect, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA.
[Zingone, Adriana; Costello, Rene; Zhang, Yong; Korde, Neha; Landgren, Ola] NCI, Multiple Myeloma Sect, Metab Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
[Roccaro, Aldo M.; Ghobrial, Irene M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA.
RP Calvo, KR (reprint author), NIH, Hematol Sect, Dept Lab Med, Ctr Clin, 10 Ctr Dr,Bldg 10-2C306, Bethesda, MD 20892 USA.
EM calvok@cc.nih.gov
OI Roccaro, Aldo/0000-0002-1872-5128
FU Intramural NIH HHS
NR 56
TC 3
Z9 4
U1 0
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1525-1578
EI 1943-7811
J9 J MOL DIAGN
JI J. Mol. Diagn.
PD NOV
PY 2015
VL 17
IS 6
BP 669
EP 678
DI 10.1016/j.jmoldx.2015.06.006
PG 10
WC Pathology
SC Pathology
GA CU8YM
UT WOS:000363830000006
PM 26433312
ER
PT J
AU Andersen, M
Cullen, M
Boland, J
Schiffman, M
Zhang, X
Wentzensen, N
Yang, Q
Chen, Z
Yu, K
Mitchell, J
Roberson, D
Bass, S
Burdette, L
Machado, M
Ravichandran, S
Luke, B
Machiele, M
Osentoski, M
AF Andersen, M.
Cullen, M.
Boland, J.
Schiffman, M.
Zhang, X.
Wentzensen, N.
Yang, Q.
Chen, Z.
Yu, K.
Mitchell, J.
Roberson, D.
Bass, S.
Burdette, L.
Machado, M.
Ravichandran, S.
Luke, B.
Machiele, M.
Osentoski, M.
TI A New High-Throughput Tool for Exploring the Carcinogenicity and Natural
History of HPV16 Infections in Research Samples
SO JOURNAL OF MOLECULAR DIAGNOSTICS
LA English
DT Meeting Abstract
CT Annual Meeting of the Association-for-Molecular-Pathology (AMP)
CY NOV 05-07, 2015
CL Austin, TX
SP Assoc Mol Pathol
C1 [Andersen, M.; Osentoski, M.] Thermo Fisher Sci, Carlsbad, CA USA.
[Cullen, M.; Boland, J.; Schiffman, M.; Zhang, X.; Wentzensen, N.; Yang, Q.; Yu, K.; Mitchell, J.; Roberson, D.; Bass, S.; Burdette, L.; Machiele, M.] NCI, Rockville, MD USA.
[Chen, Z.] Albert Einstein Coll Med, Bronx, NY 10467 USA.
[Machado, M.] Univ Fed Minas Gerais, Inst Ciencias Biol, Belo Horizonte, MG, Brazil.
[Ravichandran, S.; Luke, B.] Frederick Natl Lab Canc Res, Frederick, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1525-1578
EI 1943-7811
J9 J MOL DIAGN
JI J. Mol. Diagn.
PD NOV
PY 2015
VL 17
IS 6
MA ID07
BP 780
EP 780
PG 1
WC Pathology
SC Pathology
GA CU8YM
UT WOS:000363830000129
ER
PT J
AU Jour, G
Wang, L
Midha, S
Zehir, AA
Chen, W
Sadowska, J
Healey, J
Choi, LL
Agaram, N
Nafa, K
Hameed, M
AF Jour, G.
Wang, L.
Midha, S.
Zehir, A. Ahmet
Chen, W.
Sadowska, J.
Healey, J.
Choi, L. Lisa
Agaram, N.
Nafa, K.
Hameed, M.
TI The Molecular Landscape of Extraskeletal Osteosarcoma
SO JOURNAL OF MOLECULAR DIAGNOSTICS
LA English
DT Meeting Abstract
CT Annual Meeting of the Association-for-Molecular-Pathology (AMP)
CY NOV 05-07, 2015
CL Austin, TX
SP Assoc Mol Pathol
C1 [Jour, G.; Wang, L.; Midha, S.; Zehir, A. Ahmet; Sadowska, J.; Healey, J.; Choi, L. Lisa; Agaram, N.; Nafa, K.; Hameed, M.] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
[Chen, W.] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1525-1578
EI 1943-7811
J9 J MOL DIAGN
JI J. Mol. Diagn.
PD NOV
PY 2015
VL 17
IS 6
MA ST45
BP 823
EP 823
PG 1
WC Pathology
SC Pathology
GA CU8YM
UT WOS:000363830000305
ER
PT J
AU Huang, CE
Dickens, J
Konigshofer, Y
Vemula, R
Lih, J
Sims, D
Williams, M
Garlick, R
Anekella, B
AF Huang, C. E.
Dickens, J.
Konigshofer, Y.
Vemula, R.
Lih, J.
Sims, D.
Williams, M.
Garlick, R.
Anekella, B.
TI Development of Highly Multiplexed, Semi-Quantitative Reference Materials
for Somatic Tumor Mutation Profiling
SO JOURNAL OF MOLECULAR DIAGNOSTICS
LA English
DT Meeting Abstract
CT Annual Meeting of the Association-for-Molecular-Pathology (AMP)
CY NOV 05-07, 2015
CL Austin, TX
SP Assoc Mol Pathol
C1 [Huang, C. E.; Dickens, J.; Konigshofer, Y.; Vemula, R.; Anekella, B.] SeraCare Life Sci, Gaithersburg, MD USA.
[Lih, J.; Sims, D.; Williams, M.] NCI, Frederick Lab Canc Res, Frederick, MD 21701 USA.
[Garlick, R.] SeraCare Life Sci, Milford, MA USA.
RI Dickens, James/H-5993-2016
NR 0
TC 0
Z9 0
U1 1
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1525-1578
EI 1943-7811
J9 J MOL DIAGN
JI J. Mol. Diagn.
PD NOV
PY 2015
VL 17
IS 6
MA TT59
BP 857
EP 858
PG 2
WC Pathology
SC Pathology
GA CU8YM
UT WOS:000363830000447
ER
PT J
AU Barcus, M
Rao, A
Golubeva, Y
Ardlie, K
Branton, P
Roche, N
Sobin, L
Valentino, K
Warner, A
Moore, H
AF Barcus, M.
Rao, A.
Golubeva, Y.
Ardlie, K.
Branton, P.
Roche, N.
Sobin, L.
Valentino, K.
Warner, A.
Moore, H.
TI Laser Capture Microdissection (LCM) of PAXgene-Fixed Paraffin-Embedded
(PFPE) Specimens, a Genotype Tissue-Expression (GTEx) Pilot Project
SO JOURNAL OF MOLECULAR DIAGNOSTICS
LA English
DT Meeting Abstract
CT Annual Meeting of the Association-for-Molecular-Pathology (AMP)
CY NOV 05-07, 2015
CL Austin, TX
SP Assoc Mol Pathol
C1 [Barcus, M.; Golubeva, Y.; Roche, N.; Sobin, L.; Valentino, K.; Warner, A.] Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
[Rao, A.; Branton, P.; Moore, H.] NCI, Rockville, MD USA.
[Ardlie, K.] Broad Inst, Cambridge, MA USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1525-1578
EI 1943-7811
J9 J MOL DIAGN
JI J. Mol. Diagn.
PD NOV
PY 2015
VL 17
IS 6
MA TT61
BP 858
EP 858
PG 1
WC Pathology
SC Pathology
GA CU8YM
UT WOS:000363830000449
ER
PT J
AU Tam, J
Merino, D
AF Tam, Johnny
Merino, David
TI Stochastic optical reconstruction microscopy (STORM) in comparison with
stimulated emission depletion (STED) and other imaging methods
SO JOURNAL OF NEUROCHEMISTRY
LA English
DT Review
DE confocal; fluorescence microscopy; stimulated emission depletion;
stochastic optical reconstruction microscopy; super resolution; total
internal reflectance fluorescence
ID PHOTOACTIVATED LOCALIZATION MICROSCOPY; STRUCTURED-ILLUMINATION
MICROSCOPY; DIFFRACTION RESOLUTION BARRIER; FIELD FLUORESCENCE
MICROSCOPY; GROUND-STATE-DEPLETION; SUPERRESOLUTION MICROSCOPY;
NANOSCALE RESOLUTION; SUBDIFFRACTION-RESOLUTION; LATERAL RESOLUTION;
SCALE RESOLUTION
AB Stochastic optical reconstruction microscopy (STORM) and stimulated emission depletion (STED) microscopy are two super-resolution optical microscopy approaches that have rapidly gained popularity in recent years. Both modalities offer super-resolution imaging capabilities with the potential for imaging in multiple colors, three-dimensions, and the possibility to image in live cells. In this review, we focus on the specific advantages and disadvantages of each technique in the context of each other. STORM has been reported to achieve higher spatial resolution when compared to STED, but a lengthy acquisition may be required. STED utilizes relatively higher laser intensities, but is able to generate a super-resolution image immediately after acquisition without the need for any additional data processing. Ultimately, the choice between STORM and STED will depend not only on the specific application, but also on the users' ability to understand and optimize the various parameters ranging from sample preparation to image acquisition, which determine the quality of the final image.
C1 [Tam, Johnny] NEI, NIH, Bethesda, MD 20892 USA.
[Merino, David] ICFO Inst Ciencies Foton, Barcelona, Spain.
RP Tam, J (reprint author), NEI, NIH, Bethesda, MD 20892 USA.
EM johnny@nih.gov
RI Merino, David/G-5179-2015
OI Merino, David/0000-0002-0119-9459
NR 103
TC 5
Z9 6
U1 19
U2 85
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 NOV
PY 2015
VL 135
IS 4
BP 643
EP 658
DI 10.1111/jnc.13257
PG 16
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA CV9ZV
UT WOS:000364649300002
PM 26222552
ER
PT J
AU Jacobson, O
Weiss, ID
Wang, L
Wang, Z
Yang, XY
Dewhurst, A
Ma, Y
Zhu, GZ
Niu, G
Kiesewetter, DO
Vasdev, N
Liang, SH
Chen, XY
AF Jacobson, Orit
Weiss, Ido D.
Wang, Lu
Wang, Zhe
Yang, Xiangyu
Dewhurst, Andrew
Ma, Ying
Zhu, Guizhi
Niu, Gang
Kiesewetter, Dale O.
Vasdev, Neil
Liang, Steven H.
Chen, Xiaoyuan
TI F-18-Labeled Single-Stranded DNA Aptamer for PET Imaging of Protein
Tyrosine Kinase-7 Expression
SO JOURNAL OF NUCLEAR MEDICINE
LA English
DT Article
DE PTK7; PET imaging; F-18; click chemistry; ssDNA aptamer
ID CELL POLARITY; PTK7; CANCER; REGULATOR; CARCINOMA; LEUKEMIA; FAMILY;
PROBES; GENES; ROLES
AB Protein tyrosine kinase-7 (PTK7), a member of receptor tyrosine kinase superfamily initially identified as colon carcinoma kinase-4, is highly expressed in various human malignancies. Its expression was found to correlate with aggressive biologic behaviors such as increased cell proliferation, invasiveness, and migration. Despite the importance and unmet need of imaging PTK7 in vivo, there is currently no clinically relevant method to visualize tumoral PTK7 expression noninvasively such as PET or SPEC. This study aimed to develop a specific, selective, and high-affinity PET radioligand based on single-stranded DNA aptamer to address this challenge. Methods: Sgc8, a 41-oligonucleotide that targets to PTK7, was labeled with F-18 using a 2-step radiochemical synthesis, which featured a direct 1-step radio-fluorination on the distinctive spirocyclic hypervalent iodine(III) precursor to give F-18-fluorobenzyl azide followed by copper-mediated click conjugation with Sgc8-allcyne. F-18-Sgc8 was evaluated in vitro and in vivo in 2 cell lines, HCT116 and U87MG, which express high and low amounts of PTK7, respectively. Results: Sgc8 was labeled efficiently with F-18 in an isolated radiochemical yield of 62% 2%, non decay-corrected based on F-18-fluorobenzyl azide. F-18-Tr-Sgc8 was found to possess high-affinity binding to both cell lines, with binding affinity values of 2.7 +/- 0.6 nM for HCT116 and 16.9 +/- 2.1 nM for U87MG. In vivo PET imaging clearly visualized PTK7 expression in HCT116 xenografted mice, with tumor uptake of 0.76 +/- 0.09 percentage injected dose per gram (%ID/g) at 30 min after injection for the subcutaneous tumor model and greater than 1.5 %ID/g for the liver metastasis model. U87MG xenograft tumors had much lower tracer accumulation (0.13 +/- 0.06 %ID/g at 30 min after injection), which was consistent with the lower expression of PTK7 in this tumor model. The labeled aptamer was rapidly cleared from the blood through the kidneys and bladder to give high tumor-to-blood and tumor-to-muscle ratios of 7.29 +/- 1.51 and 10.25 +/- 2.08, respectively. Conclusion: The F-18-radiolabeling methodology shown here is a robust procedure for labeling aptamers and similar chemical moieties and can be applied to many different targets. Quantification of PTK7 using F-18-Tr-Sgc8 may be suitable for clinical translation and might help in the future to select and monitor appropriate therapies.
C1 [Jacobson, Orit; Wang, Zhe; Yang, Xiangyu; Dewhurst, Andrew; Ma, Ying; Zhu, Guizhi; Niu, Gang; Kiesewetter, Dale O.; Chen, Xiaoyuan] Natl Inst Biomed Imaging & Bioengn, Lab Mol Imaging & Nanomed, NIH, Bethesda, MD USA.
[Weiss, Ido D.] NIAID, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA.
[Wang, Lu; Vasdev, Neil; Liang, Steven H.] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Nucl Med & Mol Imaging, Boston, MA 02114 USA.
[Wang, Lu; Vasdev, Neil; Liang, Steven H.] Harvard Univ, Sch Med, Dept Radiol, Boston, MA 02114 USA.
RP Chen, XY (reprint author), NIH, 35A Convent Dr,GD937, Bethesda, MD 20892 USA.
EM Liang.Steven@mgh.harvard.edu; shawn.chen@nih.gov
FU National Institute of Biomedical Imaging and Bioengineering (NIBIB),
National Institutes of Health (NIH)
FX The costs of publication of this article were defrayed in part by the
payment of page charges. Therefore, and solely to indicate this fact,
this article is hereby marked "advertisement" in accordance with 18 USC
section 1734. This work was supported by the intramural research program
of the National Institute of Biomedical Imaging and Bioengineering
(NIBIB), National Institutes of Health (NIH). No other potential
conflict of interest relevant to this article was reported.
NR 26
TC 6
Z9 6
U1 16
U2 33
PU SOC NUCLEAR MEDICINE INC
PI RESTON
PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA
SN 0161-5505
EI 1535-5667
J9 J NUCL MED
JI J. Nucl. Med.
PD NOV
PY 2015
VL 56
IS 11
BP 1780
EP 1785
DI 10.2967/jnumed.115.160960
PG 6
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA CV6BQ
UT WOS:000364356100027
PM 26315836
ER
PT J
AU Koenig, J
Windham, BG
Ferrucci, L
Sonntag, D
Fischer, JE
Thayer, JF
Jarczok, MN
AF Koenig, J.
Windham, B. G.
Ferrucci, L.
Sonntag, D.
Fischer, J. E.
Thayer, J. F.
Jarczok, M. N.
TI Association strength of three adiposity measures with autonomic nervous
system function in apparently healthy employees
SO JOURNAL OF NUTRITION HEALTH & AGING
LA English
DT Article
DE Adiposity; autonomic nervous system; heart rate variability; body mass
index; waist circumference; waist-to-height ratio
ID HEART-RATE-VARIABILITY; BODY-MASS INDEX; RISK-FACTORS; OBESITY; DISEASE
AB To investigate the association of different measures of central (abdominal) and overall adiposity with autonomic nervous system (ANS) function, indexed by heart rate variability (HRV), in apparently healthy human adults.
Cross-sectional data of 8,538 participants (20% female, age: 41 +/- 11 years, body mass index (BMI): 24 +/- 4 kg/m2, waist circumference (WC): 91 +/- 12 cm, waist-to-height ratio (WHtR): 0.45 +/- 0.08) were available for analysis.
All measures of adiposity were inversely correlated with vagally-mediated HRV indexed by RMSSD (all p < 0.001). Strongest associations were found with WC and RMSSD (r = -0.29). Associations were stronger in males (WC r = -0.32) than in females (WC r = -0.23). Partial correlations revealed the same pattern for RMSSD (WC all pcc = -0.12 p < 0.001; WC male pcc = -0.14 p < 0.001; WC female pcc = -0.06 p < 0.05). Correlation strength of BMI and WHtR with RMSSD were similar and significantly weaker compared to WC (p <.001) in unadjusted analysis. Overall, nonparametric Kendall's tb led to the same conclusions.
The present data supports previous findings, that HRV is related to measures of adiposity in healthy individuals. In line with previous research, we found that WC is more strongly related to measures of HRV, indicating that WC best captures adiposity related risk.
C1 [Koenig, J.; Thayer, J. F.] Ohio State Univ, Dept Psychol, Columbus, OH 43210 USA.
[Windham, B. G.] Univ Mississippi, Med Ctr, Dept Med, Div Geriatr, Jackson, MS 39216 USA.
[Ferrucci, L.] NIA, Longitudinal Studies Sect, Clin Res Branch, Intramural Res Program,NIH, Baltimore, MD 21224 USA.
[Sonntag, D.; Fischer, J. E.; Jarczok, M. N.] Heidelberg Univ, Mannheim Med Fac, Mannheim Inst Publ Hlth Social & Prevent Med, Mannheim, Germany.
RP Koenig, J (reprint author), Ohio State Univ, Dept Psychol, Columbus, OH 43210 USA.
EM koenig.393@osu.edu
RI Jarczok, Marc/A-2383-2014;
OI Jarczok, Marc/0000-0002-6055-385X; Koenig, Julian/0000-0003-1009-9625
NR 21
TC 2
Z9 2
U1 2
U2 3
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 NOV
PY 2015
VL 19
IS 9
BP 879
EP 882
DI 10.1007/s12603-015-0508-x
PG 4
WC Geriatrics & Gerontology; Nutrition & Dietetics
SC Geriatrics & Gerontology; Nutrition & Dietetics
GA CV8ZP
UT WOS:000364577300002
PM 26482688
ER
PT J
AU Darbari, DS
Hampson, JP
Ichesco, E
Kadom, N
Vezina, G
Evangelou, I
Clauw, DJ
Taylor, JG
Harris, RE
AF Darbari, Deepika S.
Hampson, Johnson P.
Ichesco, Eric
Kadom, Nadja
Vezina, Gilbert
Evangelou, Iordanis
Clauw, Daniel J.
Taylor, James G.
Harris, Richard E.
TI Frequency of Hospitalizations for Pain and Association With Altered
Brain Network Connectivity in Sickle Cell Disease
SO JOURNAL OF PAIN
LA English
DT Article
DE Sickle cell disease; pain; brain network connectivity; functional
neuroimaging
ID INDEPENDENT COMPONENT ANALYSIS; RESTING-STATE CONNECTIVITY; HEALTH-CARE
UTILIZATION; HYDROXYUREA TREATMENT; FIBROMYALGIA; MECHANISMS; INSULA;
ANEMIA; ADULTS; MODULATION
AB Sickle cell disease (SCD) is a hemoglobinopathy that affects more than 100,000 individuals in the United States. The disease is characterized by the presence of sickle hemoglobin and recurrent episodes of pain. Some individuals with SCD experience frequent hospitalizations and a high burden of pain. The role of central mechanisms in SCD pain has not been explored. Twenty-five adolescents and young adults with SCD underwent functional magnetic resonance imaging. Participants were stratified into groups with high pain or low pain based on the number of hospitalizations for pain in the preceding 12 months. Resting state functional connectivity was analyzed using seed-based and dual regression independent component analysis. Intrinsic brain connectivity was compared between the high pain and low pain groups, and association with fetal hemoglobin, a known modifier of SCD, was explored. Patients in the high pain group displayed an excess of pronociceptive connectivity such as between anterior cingulate and default mode network structures, such as the precuneus, whereas patients in the low pain group showed more connectivity to antinociceptive structures such as the perigenual and subgenual cingulate. Although a similar proportion of patients in both groups reported that they were on hydroxyurea, the fetal hemoglobin levels were significantly higher in the low pain group and were associated with greater connectivity to antinociceptive structures. These findings support the role of central mechanisms in SCD pain. Intrinsic brain connectivity should be explored as a complementary and objective outcome measure in SCD pain research.
Perspective: Altered connectivity patterns associated with high pain experience in patients with sickle cell disease suggest a possible role of central mechanisms in sickle cell pain. Resting state brain connectivity studies should be explored as an effective methodology to investigate pain in SCD. (C) 2015 by the American Pain Society
C1 [Darbari, Deepika S.] Childrens Natl Hlth Syst, Ctr Canc & Blood Disorders, Div Hematol, Washington, DC USA.
[Vezina, Gilbert; Evangelou, Iordanis] Childrens Natl Hlth Syst, Dept Diagnost Imaging & Radiol, Washington, DC USA.
[Darbari, Deepika S.; Vezina, Gilbert] George Washington Univ, Sch Med & Hlth Sci, Dept Pediat, Washington, DC 20010 USA.
[Darbari, Deepika S.; Evangelou, Iordanis; Taylor, James G.] NHLBI, Genom Med Sect, Hematol Branch, NIH, Bethesda, MD 20892 USA.
[Hampson, Johnson P.; Ichesco, Eric; Clauw, Daniel J.; Harris, Richard E.] Univ Michigan, Dept Anesthesiol, Chron Pain & Fatigue Res Ctr, Ann Arbor, MI 48109 USA.
[Kadom, Nadja] Boston Univ, Med Ctr, Dept Radiol, Boston, MA 02118 USA.
RP Darbari, DS (reprint author), George Washington Univ, Sch Med & Hlth Sci, Childrens Natl Hlth Syst,Dept Pediat, Div Hematol,Ctr Canc & Blood Disorders, 111 Michigan Ave NW, Washington, DC 20010 USA.
EM ddarbari@childrensnational.org
OI Taylor, James/0000-0002-4421-1809
FU intramural research programs of National Heart, Lung and Blood Institute
[1 ZIA HL006012, 1 ZIA HL006160]
FX This work was supported by the intramural research programs of the
National Heart, Lung and Blood Institute; contract grant numbers: 1 ZIA
HL006012; 1 ZIA HL006160 (J.G.T.). The authors declare no competing
conflicts of interest.
NR 44
TC 4
Z9 4
U1 0
U2 6
PU CHURCHILL LIVINGSTONE
PI EDINBURGH
PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE,
LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND
SN 1526-5900
J9 J PAIN
JI J. Pain
PD NOV
PY 2015
VL 16
IS 11
BP 1077
EP 1086
DI 10.1016/j.jpain.2015.07.005
PG 10
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA CV9MX
UT WOS:000364612400002
PM 26291276
ER
PT J
AU Nahin, RL
Stussman, BJ
Herman, PM
AF Nahin, Richard L.
Stussman, Barbara J.
Herman, Patricia M.
TI Out-Of-Pocket Expenditures on Complementary Health Approaches Associated
With Painful Health Conditions in a Nationally Representative Adult
Sample
SO JOURNAL OF PAIN
LA English
DT Article
DE Complementary and alternative medicine; out-of-pocket costs;
expenditures; back pain; chronic pain
ID ALTERNATIVE MEDICINE PROVIDERS; UNITED-STATES; INTERVIEW SURVEY;
INSURANCE-COVERAGE; CARE EXPENDITURES; BACK-PAIN; COST DATA; PATTERNS;
OSTEOARTHRITIS; INDIVIDUALS
AB National surveys suggest that millions of adults in the United States use complementary health approaches such as acupuncture, chiropractic manipulation, and herbal medicines to manage painful conditions such as arthritis, back pain, and fibromyalgia. Yet, national and per person out-of-pocket (OOP) costs attributable to this condition-specific use are unknown. In the 2007 National Health Interview Survey, the use of complementary health approaches, the reasons for this use, and the associated OOP costs were captured in a nationally representative sample of 5,467 adults. Ordinary least square regression models that controlled for comorbid conditions were used to estimate aggregate and per person OOP costs associated with 14 painful health conditions. Individuals using complementary approaches spent a total of $14.9 billion (standard error [SE] = $.9 billion) on these approaches to manage these painful conditions. Total OOP expenditures by those using complementary approaches for their back pain ($8.7 billion, SE = $.8 billion) far outstripped OOP expenditures for any other condition; the majority of these costs ($4.7 billion, SE = $.4 billion) were for visits to complementary providers. Annual condition-specific per person OOP costs varied from a low of $568 (SE = $144) for regular headaches to a high of $895 (SE = $163) for fibromyalgia.
Perspective: Adults in the United States spent $14.9 billion on complementary health approaches (eg, acupuncture, chiropractic manipulation, and herbal medicines) to manage painful conditions including back pain ($8.7 billion). This back pain estimate is almost one-third of the total conventional health care expenditure for back pain ($30.4 billion) and two-thirds higher than conventional OOP expenditures ($5.1 billion). Published by Elsevier Inc. on behalf of the American Pain Society
C1 [Nahin, Richard L.; Stussman, Barbara J.] NIH, Natl Ctr Complementary & Integrat Hlth, Bethesda, MD 20892 USA.
[Herman, Patricia M.] RAND Corp, RAND Hlth, Santa Monica, CA USA.
RP Nahin, RL (reprint author), NIH, Natl Ctr Complementary & Integrat Hlth, 6707 Democracy Blvd,Suite 401, Bethesda, MD 20892 USA.
EM nahinr@mail.nih.gov
OI Nahin, Richard/0000-0002-3682-4816
FU Intramural NIH HHS [Z99 AT999999]
NR 47
TC 2
Z9 2
U1 2
U2 6
PU CHURCHILL LIVINGSTONE
PI EDINBURGH
PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE,
LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND
SN 1526-5900
J9 J PAIN
JI J. Pain
PD NOV
PY 2015
VL 16
IS 11
BP 1147
EP 1162
DI 10.1016/j.jpain.2015.07.013
PG 16
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA CV9MX
UT WOS:000364612400009
PM 26320946
ER
PT J
AU Hernandez-Andrade, E
Garcia, M
Ahn, H
Korzeniewski, SJ
Saker, H
Yeo, L
Chaiworapongsa, T
Hassan, SS
Romero, R
AF Hernandez-Andrade, Edgar
Garcia, Maynor
Ahn, Hyunyoung
Korzeniewski, Steven J.
Saker, Homam
Yeo, Lami
Chaiworapongsa, Tinnakorn
Hassan, Sonia S.
Romero, Roberto
TI Strain at the internal cervical os assessed with quasi-static
elastography is associated with the risk of spontaneous preterm delivery
at <= 34 weeks of gestation
SO JOURNAL OF PERINATAL MEDICINE
LA English
DT Article
DE Cervical elasticity; cervical stiffness; prematurity; preterm labor;
short cervix
ID HUMAN UTERINE CERVIX; SONOGRAPHIC SHORT CERVIX; EARLY TERM INFANTS;
SHEAR-WAVE SPEED; IN-VIVO; QUANTITATIVE ELASTOGRAPHY; BIOMECHANICAL
PROPERTIES; MECHANICAL-PROPERTIES; EXTRACELLULAR-MATRIX; ASYMPTOMATIC
WOMEN
AB Aim: To evaluate the association between cervical strain assessed with quasi-static elastography and spontaneous preterm delivery.
Methods: Quasi-static elastography was used to estimate cervical strain in 545 pregnant women with singleton pregnancies from 11 weeks to 28 weeks of gestation. Cervical strain was evaluated in one sagittal plane and in the cross-sectional planes of the internal cervical os and external cervical os. The distribution of strain values was categorized into quartiles for each studied region and their association with spontaneous preterm delivery at <= 34 weeks and at < 37 weeks of gestation was evaluated using logistic regression.
Results: The prevalence of spontaneous preterm delivery at < 37 weeks of gestation was 8.2% (n=45), and that at <= 34 weeks of gestation was 3.8% (n=21). Strain in the internal cervical os was the only elastography value associated with spontaneous preterm delivery. Women with strain values in the 3rd and 4th quartiles had a significantly higher risk of spontaneous preterm delivery at <= 34 weeks and at < 37 weeks of gestation when compared to women with strain values in the lowest quartile. When adjusting for a short cervix (< 25 mm) and gestational age at examination, women with strain values in the 3rd quartile maintained a significant association with spontaneous preterm delivery at <= 34 weeks (OR 9.0; 95% CI, 1.1-74.0; P=0.02), whereas women with strain values in the highest quartile were marginally more likely than women with lowest quartile strain values to deliver spontaneously at < 37 weeks of gestation (OR 95% CI: 2.8; [0.9-9.0]; P=0.08).
Conclusion: Increased strain in the internal cervical os is associated with higher risk of spontaneous preterm delivery both at <= 34 and < 37 weeks of gestation.
C1 [Romero, Roberto] Wayne State Univ, Hutzel Womens Hosp, Perinatol Res Branch, NICHD,NIH,DHHS, Detroit, MI 48201 USA.
[Korzeniewski, Steven J.; Romero, Roberto] Michigan State Univ, Dept Epidemiol & Biostat, E Lansing, MI 48824 USA.
[Romero, Roberto] Univ Michigan, Dept Obstet & Gynecol, Ann Arbor, MI 48109 USA.
[Hernandez-Andrade, Edgar; Garcia, Maynor; Ahn, Hyunyoung; Korzeniewski, Steven J.; Saker, Homam; Yeo, Lami; Chaiworapongsa, Tinnakorn; Hassan, Sonia S.] NICHD, Perinatol Res Branch, NIH, US Dept HHS, Detroit, MI USA.
[Hernandez-Andrade, Edgar; Garcia, Maynor; Ahn, Hyunyoung; Korzeniewski, Steven J.; Saker, Homam; Yeo, Lami; Chaiworapongsa, Tinnakorn; Hassan, Sonia S.] NICHD, Perinatol Res Branch, NIH, US Dept HHS, Bethesda, MD USA.
[Hernandez-Andrade, Edgar; Garcia, Maynor; Ahn, Hyunyoung; Korzeniewski, Steven J.; Saker, Homam; Yeo, Lami; Chaiworapongsa, Tinnakorn; Hassan, Sonia S.] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA.
RP Romero, R (reprint author), Wayne State Univ, Hutzel Womens Hosp, Perinatol Res Branch, NICHD,NIH,DHHS, 3990 John R,4 Brush, Detroit, MI 48201 USA.
EM ehernand@med.wayne.edu; romeror@mail.nih.gov
FU Federal funds from the NICHD/NIH/DHHS [HHSN275201300006C]; Perinatology
Research Branch, Division of Intramural Research, Eunice Kennedy Shriver
National Institute of Child Health and Human Development, National
Institutes of Health, Department of Health and Human Services
(NICHD/NIH/DHHS)
FX This research was supported, in part, by the Perinatology Research
Branch, Division of Intramural Research, Eunice Kennedy Shriver National
Institute of Child Health and Human Development, National Institutes of
Health, Department of Health and Human Services (NICHD/NIH/DHHS); and,
in part, with Federal funds from the NICHD/NIH/DHHS under Contract No.
HHSN275201300006C. The ultrasound experience and technical support of
senior Registered Diagnostic Medical Sonographers (RDMS) Catherine
Ducharme and Denise Haggerty are gratefully acknowledged.
NR 92
TC 1
Z9 2
U1 2
U2 3
PU WALTER DE GRUYTER GMBH
PI BERLIN
PA GENTHINER STRASSE 13, D-10785 BERLIN, GERMANY
SN 0300-5577
EI 1619-3997
J9 J PERINAT MED
JI J. Perinat. Med.
PD NOV
PY 2015
VL 43
IS 6
BP 657
EP 666
DI 10.1515/jpm-2014-0382
PG 10
WC Obstetrics & Gynecology; Pediatrics
SC Obstetrics & Gynecology; Pediatrics
GA CV9AM
UT WOS:000364579700003
PM 25781664
ER
PT J
AU Kumar, A
Baycin-Hizal, D
Wolozny, D
Pedersen, LE
Lewis, NE
Heffner, K
Chaerkady, R
Cole, RN
Shiloach, J
Zhang, H
Bowen, MA
Betenbaugh, MJ
AF Kumar, Amit
Baycin-Hizal, Deniz
Wolozny, Daniel
Pedersen, Lasse Ebdrup
Lewis, Nathan E.
Heffner, Kelley
Chaerkady, Raghothama
Cole, Robert N.
Shiloach, Joseph
Zhang, Hui
Bowen, Michael A.
Betenbaugh, Michael J.
TI Elucidation of the CHO Super-Ome (CHO-SO) by Proteoinformatics
SO JOURNAL OF PROTEOME RESEARCH
LA English
DT Article
DE proteomics; secretome; CHO; signal peptides; ontology; host cell
proteins; immunogenicity
ID HAMSTER OVARY CELLS; INTEGRIN-LINKED KINASE; SECRETED PROTEIN
PREDICTION; GROWTH-FACTOR-BETA; TIME-OF-FLIGHT; PROTEOMIC ANALYSIS;
INTRAVENOUS IMMUNOGLOBULINS; RAPID CHARACTERIZATION;
EXTRACELLULAR-MATRIX; REGULATED EXOCYTOSIS
AB Chinese hamster ovary (CHO) cells are the preferred host cell line for manufacturing a variety of complex biotherapeutic drugs including monoclonal antibodies. We performed a proteomics and bioinformatics analysis on the spent medium from adherent CHO cells. Supernatant from CHO-K1 culture was collected and subjected to in-solution digestion followed by LC/LC-MS/MS analysis, which allowed the identification of 3281 different host cell proteins (HCPs). To functionally categorize them, we applied multiple bioinformatics tools to the proteins identified in our study including SignalP, TargetP, SecretomeP, TMHMM, WoLF PSORT, and Phobius. This analysis provided information on the presence of signal peptides, transmembrane domains, and cellular localization and showed that both secreted and intracellular proteins were constituents of the supernatant. Identified proteins were shown to be localized to the secretory pathway including ones playing roles in cell growth, proliferation, and folding as well as those involved in protein degradation and removal. After combining proteins predicted to be secreted or having a signal peptide, we identified 1015 proteins, which we termed as CHO supernatant-ome (CHO-SO), or superome. As a part of this effort, we created a publically accessible web-based tool called GO-CHO to functionally categorize proteins found in CHO-SO and identify enriched molecular functions, biological processes, and cellular components. We also used a tool to evaluate the immunogenicity potential of high-abundance HCPs. Among enriched functions were catalytic activity and structural constituents of the cytoskeleton. Various transport related biological processes, such as vesicle mediated transport, were found to be highly enriched. Extracellular space and vesicular exosome associated proteins were found to be the most enriched cellular components. The superome also contained proteins secreted from both classical and nonclassical secretory pathways. The work and database described in our study will enable the CHO community to rapidly identify high-abundance HCPs in their cultures and therefore help assess process and purification methods used in the production of biologic drugs.
C1 [Kumar, Amit; Wolozny, Daniel; Heffner, Kelley; Betenbaugh, Michael J.] Johns Hopkins Univ, Dept Chem & Biomol Engn, Baltimore, MD 21218 USA.
[Kumar, Amit; Shiloach, Joseph] NIDDK, Biotechnol Core Lab, NIH, Bethesda, MD 20892 USA.
[Pedersen, Lasse Ebdrup] Tech Univ Denmark, Novo Nordisk Fdn Ctr Biosustainabil, DK-2970 Horsholm, Denmark.
[Lewis, Nathan E.] Brigham Young Univ, Dept Biol, Provo, UT 84602 USA.
[Lewis, Nathan E.] Univ Calif San Diego, Dept Pediat, La Jolla, CA 92093 USA.
[Chaerkady, Raghothama; Cole, Robert N.] Johns Hopkins Univ, Sch Med, Mass Spectrometry & Prote Facil, Inst Basic Biomed Sci, Baltimore, MD 21205 USA.
[Zhang, Hui] Johns Hopkins Sch Med, Dept Pathol, Baltimore, MD 21287 USA.
[Baycin-Hizal, Deniz; Bowen, Michael A.] MedImmune LLC, Antibody Discovery & Prot Engn, Gaithersburg, MD 20878 USA.
RP Betenbaugh, MJ (reprint author), Johns Hopkins Univ, Dept Chem & Biomol Engn, Baltimore, MD 21218 USA.
EM beten@jhu.edu
OI Pedersen, Lasse Ebdrup/0000-0002-6064-919X; Lewis,
Nathan/0000-0001-7700-3654
FU MedImmune LLC; Intramural program of the National Institute of Diabetes
and Digestive and Kidney Diseases, National Institutes of Health
FX Funding for the study was provided by MedImmune LLC and the Intramural
program of the National Institute of Diabetes and Digestive and Kidney
Diseases, National Institutes of Health. The funders had no role in
study design, data collection and analysis, or preparation of the
manuscript.
NR 121
TC 2
Z9 2
U1 5
U2 17
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1535-3893
EI 1535-3907
J9 J PROTEOME RES
JI J. Proteome Res.
PD NOV
PY 2015
VL 14
IS 11
BP 4687
EP 4703
DI 10.1021/acs.jproteome.5b00588
PG 17
WC Biochemical Research Methods
SC Biochemistry & Molecular Biology
GA CV7EL
UT WOS:000364435100022
PM 26418914
ER
PT J
AU Brooks-Russell, A
Conway, KP
Liu, DP
Xie, YL
Vullo, GC
Li, KG
Iannotti, RJ
Compton, W
Simons-Morton, B
AF Brooks-Russell, Ashley
Conway, Kevin P.
Liu, Danping
Xie, Yunlong
Vullo, Genevieve C.
Li, Kaigang
Iannotti, Ronald J.
Compton, Wilson
Simons-Morton, Bruce
TI Dynamic Patterns of Adolescent Substance Use: Results From a Nationally
Representative Sample of High School Students
SO JOURNAL OF STUDIES ON ALCOHOL AND DRUGS
LA English
DT Article
ID LATENT CLASS ANALYSIS; ALCOHOL-USE; PARENTING PRACTICES; PROTECTIVE
FACTORS; YOUNG ADULTHOOD; RISK BEHAVIORS; COOCCURRENCE; CONSEQUENCES;
TRAJECTORIES; PREVALENCE
AB Objective: Use of tobacco, alcohol, marijuana, and other drugs increases during the high school years, yet little is known about individual patterns over time, particularly patterns of contemporaneous multiple-substance use. This study examined trajectories of contemporaneous substance use and how individual and social factors differentially predict patterns of substance use. Method: Longitudinal trajectories of substance use were examined in a nationally representative sample of students (N = 2,512) over a 3-year period (10th through 12th grades) using latent class analysis. Individual, parental, and peer risk factors in 10th grade were examined in relation to membership in trajectory classes. Result: A five-class model was identified: nonusers (45.5%); tobacco, alcohol, and other drug users (9.2%); alcohol and other drug users (9.2%); increasing multiple-substance users (16.7%); and decreasing multiple-substance users (19.4%). Depressive symptoms at baseline were associated with a higher likelihood of membership in all classes except the increasing multiple-substance-user class, but the association becomes insignificant when social influence factors were adjusted. Parental-monitoring knowledge was associated with a lower likelihood of membership in all classes except increasing multiple-substance-user class, whereas perceived parental disapproval was associated with a lower likelihood of membership in the tobacco, alcohol, and other drug user class. Peer substance use was associated with a higher likelihood of membership in each of the substance use classes. Conclusions: The identified longitudinal profiles highlight the pervasiveness and dynamic patterns of contemporaneous multiple-substance use during 10th through 12th grades. Negative peer influence increased risk, whereas positive parenting behaviors decreased risk. The findings are consistent with the need to foster social influences and protective factors against adolescent substance use.
C1 [Brooks-Russell, Ashley] Univ Colorado, Colorado Sch Publ Hlth, Dept Community & Behav Hlth, Aurora, CO 80045 USA.
[Conway, Kevin P.; Vullo, Genevieve C.; Compton, Wilson] NIDA, Div Epidemiol Serv & Prevent Res, NIH, Bethesda, MD 20892 USA.
[Liu, Danping; Xie, Yunlong; Li, Kaigang; Simons-Morton, Bruce] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, NIH, Bethesda, MD USA.
[Xie, Yunlong] Glotech Inc, Bethesda, MD USA.
[Vullo, Genevieve C.] Kelly Govt Solut, Bethesda, MD USA.
[Iannotti, Ronald J.] Univ Massachusetts, Coll Nursing & Hlth Sci, Boston, MA 02125 USA.
RP Brooks-Russell, A (reprint author), Univ Colorado, Colorado Sch Publ Hlth, Dept Community & Behav Hlth, Anschutz Med Campus,13001 E 17th Pl B119,Bldg 500, Aurora, CO 80045 USA.
EM Ashley.brooks-russell@ucdenver.edu
OI Conway, Kevin/0000-0002-7638-339X; Simons-Morton,
Bruce/0000-0003-1099-6617
FU intramural research program of Eunice Kennedy Shriver National Institute
of Child Health and Human Development (NICHD) [HHSN267200800009C];
National Heart, Lung and Blood Institute (NHLBI); National Institute on
Alcohol Abuse and Alcoholism (NIAAA); Maternal and Child Health Bureau
(MCHB) of Health Resources and Services Administration (HRSA)
FX This research (contract number HHSN267200800009C) was supported in part
by the intramural research program of the Eunice Kennedy Shriver
National Institute of Child Health and Human Development (NICHD), and
the National Heart, Lung and Blood Institute (NHLBI), the National
Institute on Alcohol Abuse and Alcoholism (NIAAA), and the Maternal and
Child Health Bureau (MCHB) of the Health Resources and Services
Administration (HRSA), with supplemental support from the National
Institute on Drug Abuse (NIDA). The views and opinions expressed in this
article are those of the authors and do not necessarily represent the
views of NIDA, the NICHD, the National Institutes of Health, or any
other governmental agency.
NR 41
TC 1
Z9 1
U1 2
U2 6
PU ALCOHOL RES DOCUMENTATION INC CENT ALCOHOL STUD RUTGERS UNIV
PI PISCATAWAY
PA C/O DEIRDRE ENGLISH, 607 ALLISON RD, PISCATAWAY, NJ 08854-8001 USA
SN 1937-1888
EI 1938-4114
J9 J STUD ALCOHOL DRUGS
JI J. Stud. Alcohol Drugs
PD NOV
PY 2015
VL 76
IS 6
BP 962
EP 970
PG 9
WC Substance Abuse; Psychology
SC Substance Abuse; Psychology
GA CW2DQ
UT WOS:000364801700017
PM 26562606
ER
PT J
AU Baird, DD
Harmon, QE
Upson, K
Moore, KR
Barker-Cummings, C
Baker, S
Cooper, T
Wegienka, G
AF Baird, Donna D.
Harmon, Quaker E.
Upson, Kristen
Moore, Kristen R.
Barker-Cummings, Christie
Baker, Susan
Cooper, Tracy
Wegienka, Ganesa
TI A Prospective, Ultrasound-Based Study to Evaluate Risk Factors for
Uterine Fibroid Incidence and Growth: Methods and Results of Recruitment
SO JOURNAL OF WOMENS HEALTH
LA English
DT Article
ID UNITED-STATES; WOMENS HEALTH; WHITE WOMEN; VITAMIN-D; LEIOMYOMA; AGE;
PREVALENCE; EXPRESSION; QUESTIONNAIRE; HYPOTHESIS
AB Background: Uterine fibroids are common, benign, smooth-muscle tumors that can cause major morbidity for reproductive-age women, often requiring invasive treatment. Despite this personal and public health burden, no prior study has attempted to periodically screen fibroid-free women with ultrasound to detect incident disease and identify risk factors. Methods: We designed a study to prospectively investigate development of fibroids by enrolling women without a clinical diagnosis of fibroids and screening for fibroids with ultrasound at baseline. Enrollment procedures included extensive questionnaires and specimen collection (blood, urine, vaginal swabs). The cohort is followed at approximately 20-month intervals. At each follow-up there are updates to the questionnaire data, further specimen collection, and an ultrasound examination. We identify incident disease and measure tumor growth. The two exposures of primary interest are vitamin D insufficiency and reproductive tract infections. This manuscript provides a detailed description of the study methods, recruitment results, and participant characteristics. Results: The Study of Environment, Lifestyle and Fibroids enrolled 1,696 African American women aged 23-34 years. Family and friends was a leading recruitment source. More than 95% of participants contributed all the requested biological specimens at baseline. Study ultrasound examinations revealed undiagnosed fibroids in 378 women (22% of participants). The retention rate for the first follow-up was 87%. Conclusions: Study design aspects likely to be important for long-term studies in young African Americans include personalized recruitment, multiple steps to the enrollment process that rely on the initiative of the participant, and methods for tracing highly mobile study subjects.
C1 [Baird, Donna D.; Upson, Kristen; Moore, Kristen R.] NIEHS, Epidemiol Branch, NIH, Res Triangle Pk, NC 27709 USA.
[Harmon, Quaker E.; Barker-Cummings, Christie; Baker, Susan] Social & Sci Syst Inc, Durham, NC USA.
[Cooper, Tracy] Henry Ford Hlth Syst, Dept Radiol, Div Ultrasound, Detroit, MI USA.
[Wegienka, Ganesa] Henry Ford Hosp, Dept Publ Hlth Sci, Detroit, MI 48202 USA.
RP Baird, DD (reprint author), NIEHS, Epidemiol Branch, Bldg 101,Room A308,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA.
EM baird@niehs.nih.gov
RI Moore, Kristen/C-2303-2017; Upson, Kristen/D-4504-2017; Baird,
Donna/D-5214-2017;
OI Moore, Kristen/0000-0001-9993-3270; Upson, Kristen/0000-0001-9598-8776;
Baird, Donna/0000-0002-5544-2653; Harmon, Quaker/0000-0002-5866-848X
FU Intramural Research Program of the National Institutes of Health,
National Institute of Environmental Health Sciences; American Recovery
and Reinvestment Act
FX We thank the participants for sharing their valuable information and
taking time to complete the numerous study activities. Drs. Gordon Flake
and Anne Marie Jukic reviewed an earlier version of the manuscript. We
also thank the following study team members without whom the recruitment
and retention of study participants, day-to-day operations, and data and
specimen collection would not be possible: at Social and Scientific
Systems, Inc., Taylor Abernathy, Jackie Allison, Thomasina Austin, Ans
Bilhorn, Deborah Cousins, Carrissa Dixon, Suzie Dollar, Judith
Fontanelle, Elizabeth Ganze, Irina Khodush, Jason Langfahl, Christina
Makarushka, Carol Messler, Naomi Piserchia, Ellen Revak, Tina Richmond,
Diana Smith, Nick Verna, Terri Young (Westat), Fikri Yucel, and the
Telephone Research Center staff; and at HFHS, Kyra Jones, Karen
Bourgeois, Louise Brennan, Tangi Dargin, Vickie Gaines, Wanda Greene,
Yolanda Harris, Cynthia Hill, Melissa Houston, Darine Joumaa, LaSalle
McKenzie, Dojna Mototolea, Rita Norman, Debbie Williams, Evangeline
Griesemer, and LaToya Allen. This research was supported by the
Intramural Research Program of the National Institutes of Health,
National Institute of Environmental Health Sciences, and, in part, by
funds allocated for health research by the American Recovery and
Reinvestment Act.
NR 42
TC 9
Z9 9
U1 3
U2 7
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1540-9996
EI 1931-843X
J9 J WOMENS HEALTH
JI J. Womens Health
PD NOV 1
PY 2015
VL 24
IS 11
BP 907
EP 915
DI 10.1089/jwh.2015.5277
PG 9
WC Public, Environmental & Occupational Health; Medicine, General &
Internal; Obstetrics & Gynecology; Women's Studies
SC Public, Environmental & Occupational Health; General & Internal
Medicine; Obstetrics & Gynecology; Women's Studies
GA CV6SI
UT WOS:000364400300009
PM 26334691
ER
PT J
AU Kopp, JB
AF Kopp, Jeffrey B.
TI Replenishment of the podocyte compartment by parietal epithelial cells
SO KIDNEY INTERNATIONAL
LA English
DT Editorial Material
ID FOCAL SEGMENTAL GLOMERULOSCLEROSIS; RENAL PROGENITORS; DISEASE
AB While progressive podocytopenia is a characteristic feature of chronic glomerular disease, the visceral epithelial niche can be replenished from the parietal epithelium. Two new reports demonstrate this process in genetically engineered mice, using fate mapping, and in human renal biopsies manifesting segmental glomerulosclerosis in diverse settings, using cellular and extracellular matrix markers.
C1 [Kopp, Jeffrey B.] NIDDKD, Kidney Dis Branch, NIH, Bethesda, MD 20892 USA.
RP Kopp, JB (reprint author), NIDDKD, NIH, 10 Ctr Dr,3N116, Bethesda, MD 20892 USA.
EM jbkopp@nih.gov
FU Intramural NIH HHS
NR 9
TC 2
Z9 2
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0085-2538
EI 1523-1755
J9 KIDNEY INT
JI Kidney Int.
PD NOV
PY 2015
VL 88
IS 5
BP 934
EP 935
DI 10.1038/ki.2015.256
PG 2
WC Urology & Nephrology
SC Urology & Nephrology
GA CW2CR
UT WOS:000364799200002
PM 26579676
ER
PT J
AU Bouhrara, M
Spencer, RG
AF Bouhrara, Mustapha
Spencer, Richard G.
TI Incorporation of nonzero echo times in the SPGR and bSSFP signal models
used in mcDESPOT
SO MAGNETIC RESONANCE IN MEDICINE
LA English
DT Article
DE mcDESPOT; SPGR; bSSFP; quantitative MRI
ID MYELIN WATER FRACTION; WHITE-MATTER DEVELOPMENT; STOCHASTIC REGION
CONTRACTION; STATE FREE PRECESSION; STEADY-STATE; MAGNETIC-RESONANCE;
GRADIENT-ECHO; MULTICOMPONENT T-1; RELAXATION-TIME; RADIOFREQUENCY
AB PurposeTo analyze the effect of neglecting nonzero echo times (TEs) in the conventional model of multicomponent driven equilibrium single pulse observation of T-1 and T-2 (mcDESPOT).
Theory and MethodsFormulations of the two-component spoiled gradient recalled echo (SPGR) and balanced steady state free precession (bSSFP) models that incorporate nonzero TE effects are presented in the context of mcDESPOT and compared with the conventionally used SPGR and bSSFP models which ignore nonzero TEs. Relative errors in derived parameter estimates from conventional mcDESPOT, omitting TE effects, are assessed using simulations over a wide range of experimental and sample parameters.
ResultsThe neglect of nonzero TE leads to an overestimate of the SPGR signal and an underestimate of the bSSFP signal. These effects can introduce large errors in parameter estimates derived from conventional mcDESPOT under realistic imaging conditions.
ConclusionSPGR and bSSFP signal models accounting for nonzero TE effects should be incorporated into quantitative mcDESPOT analyses. Magn Reson Med 74:1227-1235, 2015. Published 2015. This article is a U.S. Government work and is in the public domain in the USA
C1 [Bouhrara, Mustapha; Spencer, Richard G.] NIA, Lab Clin Invest, NIH, Baltimore, MD 21224 USA.
RP Spencer, RG (reprint author), NIA, NIH, Intramural Res Program, BRC 04B-116,251 Bayview Blvd, Baltimore, MD 21224 USA.
EM spencer@helix.nih.gov
FU NIH, National Institute on Aging
FX We gratefully acknowledge the comments of an anonymous reviewer of a
previous publication, which led to this analysis. This work was
supported by the Intramural Research Program of the NIH, National
Institute on Aging.
NR 39
TC 4
Z9 4
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0740-3194
EI 1522-2594
J9 MAGN RESON MED
JI Magn. Reson. Med.
PD NOV
PY 2015
VL 74
IS 5
BP 1227
EP 1235
DI 10.1002/mrm.25984
PG 9
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA CV4DK
UT WOS:000364215900005
PM 26407635
ER
PT J
AU Ahmad, R
Xue, H
Giri, S
Ding, Y
Craft, J
Simonetti, OP
AF Ahmad, Rizwan
Xue, Hui
Giri, Shivraman
Ding, Yu
Craft, Jason
Simonetti, Orlando P.
TI Variable density incoherent spatiotemporal acquisition (VISTA) for
highly accelerated cardiac MRI
SO MAGNETIC RESONANCE IN MEDICINE
LA English
DT Article
DE Fekete points; Riesz energy; pseudo-random; cardiac; cine; MRI;
compressive sensing; sampling
ID T SPARSE-SENSE; CINE MRI; FEKETE POINTS; K-SPACE; RECONSTRUCTION;
RESOLUTION; RECOVERY; ERRORS
AB PurposeFor the application of compressive sensing to parallel MRI, Poisson disk sampling (PDS) has been shown to generate superior results compared with random sampling methods. However, due to its limited flexibility to incorporate additional constraints, PDS is not readily extendible to dynamic applications. Here, we propose and validate a pseudo-random sampling technique that allows incorporating constraints specific to dynamic imaging.
MethodsThe proposed sampling scheme, called variable density incoherent spatiotemporal acquisition (VISTA), is based on constrained minimization of Riesz energy on a spatiotemporal grid. Data from both a digital phantom and real-time cine were used to compare VISTA with uniform interleaved sampling (UIS) and variable density random sampling (VRS). The image quality was assessed qualitatively and quantitatively.
ResultsVISTA improved the trade-off between noise and sharpness. Also, VISTA produced diagnostic quality images at an acceleration rate of 15, whereas UIS and VRS images degraded below the diagnostic threshold at lower acceleration rates.
ConclusionsVISTA generates spatiotemporal sampling patterns with high levels of uniformity and incoherence, while maintaining a constant temporal resolution. Using a small pilot study, VISTA was shown to produce diagnostic quality images at acceleration rates up to 15. Magn Reson Med 74:1266-1278, 2015. (c) 2014 Wiley Periodicals, Inc.
C1 [Ahmad, Rizwan] Ohio State Univ, Dept Elect & Comp Engn, Columbus, OH 43210 USA.
[Xue, Hui] NIH, Bethesda, MD USA.
[Giri, Shivraman] Siemens Healthcare, Chicago, IL USA.
[Ding, Yu; Simonetti, Orlando P.] Ohio State Univ, Dorothy M Davis Heart & Lung Res Inst, Columbus, OH 43210 USA.
[Craft, Jason; Simonetti, Orlando P.] Ohio State Univ, Dept Internal Med, Div Cardiovasc Med, Columbus, OH 43210 USA.
[Simonetti, Orlando P.] Ohio State Univ, Dept Radiol, Columbus, OH 43210 USA.
RP Ahmad, R (reprint author), Ohio State Univ, 420 West 12th Ave,Room 126A, Columbus, OH 43210 USA.
EM ahmad.46@osumc.edu
FU National Heart, Lung, and Blood Institute [R01HL102450]
FX Grant sponsor: National Heart, Lung, and Blood Institute; Grant number:
R01HL102450.
NR 39
TC 3
Z9 3
U1 1
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0740-3194
EI 1522-2594
J9 MAGN RESON MED
JI Magn. Reson. Med.
PD NOV
PY 2015
VL 74
IS 5
BP 1266
EP 1278
DI 10.1002/mrm.25507
PG 13
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA CV4DK
UT WOS:000364215900009
PM 25385540
ER
PT J
AU van Gelderen, P
Mandelkow, H
de Zwart, JA
Duyn, JH
AF van Gelderen, Peter
Mandelkow, Hendrik
de Zwart, Jacco A.
Duyn, Jeff H.
TI A torque balance measurement of anisotropy of the magnetic
susceptibility in white matter
SO MAGNETIC RESONANCE IN MEDICINE
LA English
DT Article
DE white matter; magnetic susceptibility; magnetic anisotropy
ID NERVOUS-SYSTEM MYELIN; GRADIENT-ECHO MRI; HUMAN-BRAIN; MEMBRANE-LIPIDS;
DIAMAGNETIC ANISOTROPY; BIOPHYSICAL MECHANISMS; LECITHIN MEMBRANES;
ORIENTATION; CONTRAST; FIELD
AB PurposeRecent MRI studies have suggested that the magnetic susceptibility of white matter (WM) in the human brain is anisotropic, providing a new contrast mechanism for the visualization of fiber bundles and allowing the extraction of cellular compartment-specific information. This study provides an independent confirmation and quantification of this anisotropy.
MethodsAnisotropic magnetic susceptibility results in a torque exerted on WM when placed in a uniform magnetic field, tending to align the WM fibers with the field. To quantify the effect, excised spinal cord samples were placed in a torque balance inside the magnet of a 7 T MRI system and the magnetic torque was measured as function of orientation.
ResultsAll tissue samples (n=5) showed orienting effects, confirming the presence of anisotropic susceptibility. Analysis of the magnetic torque resulted in reproducible values for the WM volume anisotropy that ranged from 13.6 to 19.2 ppb.
ConclusionThe independently determined anisotropy values confirm estimates inferred from MRI experiments and validate the use of anisotropy to extract novel information about brain fiber structure and myelination. Magn Reson Med 74:1388-1396, 2015. (c) 2014 Wiley Periodicals, Inc.
C1 [van Gelderen, Peter; Mandelkow, Hendrik; de Zwart, Jacco A.; Duyn, Jeff H.] NINDS, Adv MRI Sect, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20892 USA.
RP van Gelderen, P (reprint author), NINDS, AMRI, LFMI, NIH, 10 Ctr Dr,Bldg 10,Room B1D-725, Bethesda, MD 20892 USA.
EM gelderen@nih.gov
FU National Institute of Neurological Disorders and Stroke
FX We acknowledge the Intramural Research Program of the National Institute
of Neurological Disorders and Stroke for support.
NR 38
TC 2
Z9 2
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0740-3194
EI 1522-2594
J9 MAGN RESON MED
JI Magn. Reson. Med.
PD NOV
PY 2015
VL 74
IS 5
BP 1388
EP 1396
DI 10.1002/mrm.25524
PG 9
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA CV4DK
UT WOS:000364215900020
PM 25399830
ER
PT J
AU Lang, M
Vocke, CD
Merino, MJ
Schmidt, LS
Linehan, WM
AF Lang, Martin
Vocke, Cathy D.
Merino, Maria J.
Schmidt, Laura S.
Linehan, W. Marston
TI Mitochondrial DNA mutations distinguish bilateral multifocal renal
oncocytomas from familial Birt-Hogg-Dube tumors
SO MODERN PATHOLOGY
LA English
DT Article
ID COMPLEX-I; CELL CARCINOMAS; METABOLISM; TUMORIGENESIS; DEFECTS; BIOPSY;
GENOME; CANCER; NEEDLE
AB Oncocytomas are mostly benign tumors characterized by accumulation of defective mitochondria, and in sporadic cases, are associated with disruptive mitochondrial DNA (mtDNA) mutations. However, the role mtDNA mutations have in renal tumors of Birt-Hogg-Dube (BHD) patients and other renal oncocytomas with an apparent genetic component has not been investigated to date. Here we characterize the mitochondrial genome in different renal tumors and investigate the possibility of employing mtDNA sequencing analyses of biopsy specimens to aid in the differential diagnosis of oncocytomas. The entire mitochondrial genome was sequenced in 25 samples of bilateral and multifocal (BMF) renal oncocytomas, 30 renal tumors from BHD patients and 36 non-oncocytic renal tumors of different histologies as well as in biopsy samples of kidney tumors. mtDNA sequencing in BMF oncocytomas revealed that all tumors carry disruptive mutations, which impair the assembly of the NADH-ubiquinone oxidoreductase. Multiple tumors from a given BMF oncocytoma patient mainly harbor the same somatic mutation and the kidneys of these patients display diffuse oncocytosis. In contrast, renal oncocytomas of patients with BHD syndrome and renal tumors with different histologies do not show disruptive mtDNA mutations. Moreover, we demonstrate that it is feasible to amplify and sequence the entire mtDNA in biopsy specimens, and that these sequences are representative of the tumor DNA. These results show that pathogenic mtDNA mutations affecting complex I of the respiratory chain are strongly correlated with the oncocytoma phenotype in non-BHD-related renal tumors and that mtDNA sequences from biopsies are predictive of the tumor genotype. This work supports a role for mtDNA mutations in respiratory chain complexes as diagnostic markers for renal oncocytomas.
C1 [Lang, Martin; Vocke, Cathy D.; Schmidt, Laura S.; Linehan, W. Marston] NCI, Urol Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Merino, Maria J.] NCI, Pathol Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
[Schmidt, Laura S.] Frederick Natl Lab Canc Res, Basic Sci Program, Leidos Biomed Res, Frederick, MD USA.
RP Linehan, WM (reprint author), NCI, Urol Oncol Branch, Ctr Canc Res, 9000 Rockville Pike CRC Room 1-5940W, Bethesda, MD 20892 USA.
EM WML@nih.gov
OI Lang, Martin/0000-0002-0242-6713
FU Fondazione Italiana Ricerca sul Cancro (FIRC) 'Fellowship; Intramural
Research Program of NIH, National Cancer Institute, Center for Cancer
Research; Frederick National Laboratory for Cancer Research, NTH
[HHSN261200800001E]; Associazione Italiana per la Ricerca sul Cancro
FX The present work was funded in part by Fondazione Italiana Ricerca sul
Cancro (FIRC) 'Fellowship for abroad-2011' to ML and was supported by
the Intramural Research Program of NIH, National Cancer Institute,
Center for Cancer Research. This project has been funded in part with
federal funds from the Frederick National Laboratory for Cancer
Research, NTH, under the contract HHSN261200800001E (LSS). The content
of this publication does not necessarily reflect the views or policies
of the Department of Health and Human Services, nor does mention of
trade names, commercial products or organizations imply endorsement by
the US Government. We thank Hisashi Hasumi, Yukiko Hasumi, Masaya Baba,
and Christopher Ricketts for helpful discussions and advice.
NR 43
TC 2
Z9 3
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0893-3952
EI 1530-0285
J9 MODERN PATHOL
JI Mod. Pathol.
PD NOV
PY 2015
VL 28
IS 11
BP 1458
EP 1469
DI 10.1038/modpathol.2015.101
PG 12
WC Pathology
SC Pathology
GA CV4YZ
UT WOS:000364273700006
PM 26428318
ER
PT J
AU Teicher, BA
Polley, E
Kunkel, M
Evans, D
Silvers, T
Delosh, R
Laudeman, J
Ogle, C
Reinhart, R
Selby, M
Connelly, J
Harris, E
Monks, A
Morris, J
AF Teicher, Beverly A.
Polley, Eric
Kunkel, Mark
Evans, David
Silvers, Thomas
Delosh, Rene
Laudeman, Julie
Ogle, Chad
Reinhart, Russell
Selby, Michael
Connelly, John
Harris, Erik
Monks, Anne
Morris, Joel
TI Sarcoma Cell Line Screen of Oncology Drugs and Investigational Agents
Identifies Patterns Associated with Gene and microRNA Expression
SO MOLECULAR CANCER THERAPEUTICS
LA English
DT Article
ID PRECLINICAL TESTING PROGRAM; SOFT-TISSUE SARCOMA; STAGE 1; KINASE
INHIBITOR; AURORA KINASES; EWINGS-SARCOMA; OVARIAN-CANCER; PART SARCOMA;
SENSITIVITY; APOPTOSIS
AB The diversity in sarcoma phenotype and genotype make treatment of this family of diseases exceptionally challenging. Sixty-three human adult and pediatric sarcoma lines were screened with 100 FDA-approved oncology agents and 345 investigational agents. The investigational agents' library enabled comparison of several compounds targeting the same molecular entity allowing comparison of target specificity and heterogeneity of cell line response. Gene expression was derived from exon array data and microRNA expression was derived from direct digital detection assays. The compounds were screened against each cell line at nine concentrations in triplicate with an exposure time of 96 hours using Alamar blue as the endpoint. Results are presented for inhibitors of the following targets: aurora kinase, IGF-1R, MEK, BET bromodomain, and PARP1. Chemical structures, IC50 heat maps, concentration response curves, gene expression, and miR expression heat maps are presented for selected examples. In addition, two cases of exceptional responders are presented. The drug and compound response, gene expression, and microRNA expression data are publicly available at http://sarcoma.cancer.gov. These data provide a unique resource to the cancer research community. (C) 2015 AACR.
C1 [Teicher, Beverly A.; Kunkel, Mark; Morris, Joel] NCI, Dev Therapeut Program, Div Canc Treatment & Diag, Rockville, MD USA.
[Polley, Eric] NCI, Biometr Res Branch, Div Canc Treatment & Diag, Rockville, MD USA.
[Evans, David; Silvers, Thomas; Delosh, Rene; Laudeman, Julie; Ogle, Chad; Reinhart, Russell; Selby, Michael; Connelly, John; Harris, Erik; Monks, Anne] Leidos Biomed Res Inc, Mol Pharmacol Grp, Frederick Natl Lab Canc Res, Frederick, MD USA.
RP Teicher, BA (reprint author), NCI, 9609 Med Ctr Dr, Bethesda, MD 20892 USA.
EM teicherba@mail.nih.gov
FU CCR NIH HHS [HHSN261200800001C]; Intramural NIH HHS [Z99 CA999999]; NCI
NIH HHS [HHSN261200800001E]; PHS HHS [HHSN261200800001E]
NR 69
TC 1
Z9 1
U1 2
U2 2
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1535-7163
EI 1538-8514
J9 MOL CANCER THER
JI Mol. Cancer Ther.
PD NOV
PY 2015
VL 14
IS 11
BP 2452
EP 2462
DI 10.1158/1535-7163.MCT-15-0074
PG 11
WC Oncology
SC Oncology
GA CV9FE
UT WOS:000364592000005
PM 26351324
ER
PT J
AU Seol, Y
Zhang, HL
Agama, K
Lorence, N
Pommier, Y
Neuman, KC
AF Seol, Yeonee
Zhang, Hongliang
Agama, Keli
Lorence, Nicholas
Pommier, Yves
Neuman, Keir C.
TI Single-Molecule Supercoil Relaxation Assay as a Screening Tool to
Determine the Mechanism and Efficacy of Human Topoisomerase IB
Inhibitors
SO MOLECULAR CANCER THERAPEUTICS
LA English
DT Article
ID DNA TOPOISOMERASES; ANTICANCER DRUGS; ANTITUMOR DRUGS; LAMELLARIN-D;
CAMPTOTHECIN; CLEAVAGE; COMPLEXES; TOPOLOGY; BINDING; SENSITIVITY
AB Human nuclear type IB topoisomerase (Top1) inhibitors are widely used and powerful anticancer agents. In this study, we introduce and validate a single-molecule supercoil relaxation assay as a molecular pharmacology tool for characterizing therapeutically relevant Top1 inhibitors. Using this assay, we determined the effects on Top1 supercoil relaxation activity of four Top1 inhibitors; three clinically relevant: camptothecin, LMP-400, LMP-776 (both indenoisoquinoline derivatives), and one natural product in preclinical development, lamellarin-D. Our results demonstrate that Top1 inhibitors have two distinct effects on Top1 activity: a decrease in supercoil relaxation rate and an increase in religation inhibition. The type and magnitude of the inhibition mode depend both on the specific inhibitor and on the topology of the DNA substrate. In general, the efficacy of inhibition is significantly higher with supercoiled than with relaxed DNA substrates. Comparing single-molecule inhibition with cell growth inhibition (IC50) measurements showed a correlation between the binding time of the Top1 inhibitors and their cytotoxic efficacy, independent of the mode of inhibition. This study demonstrates that the single-molecule supercoil relaxation assay is a sensitive method to elucidate the detailed mechanisms of Top1 inhibitors and is relevant for the cellular efficacy of Top1 inhibitors. (C) 2015 AACR.
C1 [Seol, Yeonee; Neuman, Keir C.] NHLBI, Lab Single Mol Biophys, NIH, Bethesda, MD 20892 USA.
[Zhang, Hongliang; Agama, Keli; Lorence, Nicholas; Pommier, Yves] NCI, Lab Mol Pharmacol, Dev Therapeut Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
RP Neuman, KC (reprint author), NIH, Room 3517,Bldg 50,50 South Dr, Bethesda, MD 20817 USA.
EM pommier@nih.gov; neumankc@mail.nih.gov
RI Neuman, Keir/F-7400-2011
OI Neuman, Keir/0000-0002-0863-5671
FU Intramural NIH HHS [Z01 BC006161-24, ZIA HL001056-03]; NCI NIH HHS [Z01
BC006161]; NHLBI NIH HHS [Z01 HL001056]
NR 42
TC 0
Z9 0
U1 1
U2 7
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1535-7163
EI 1538-8514
J9 MOL CANCER THER
JI Mol. Cancer Ther.
PD NOV
PY 2015
VL 14
IS 11
BP 2552
EP 2559
DI 10.1158/1535-7163.MCT-15-0454
PG 8
WC Oncology
SC Oncology
GA CV9FE
UT WOS:000364592000014
PM 26351326
ER
PT J
AU Adachi, T
Kobayashi, T
Sugihara, E
Yamada, T
Ikuta, K
Pittaluga, S
Saya, H
Amagai, M
Nagao, K
AF Adachi, Takeya
Kobayashi, Tetsuro
Sugihara, Eiji
Yamada, Taketo
Ikuta, Koichi
Pittaluga, Stefania
Saya, Hideyuki
Amagai, Masayuki
Nagao, Keisuke
TI Hair follicle-derived IL-7 and IL-15 mediate skin-resident memory T cell
homeostasis and lymphoma
SO NATURE MEDICINE
LA English
DT Article
ID MYCOSIS-FUNGOIDES; SEZARY-SYNDROME; STEM-CELLS; INFECTION; TISSUE;
TUMOR; EXPRESSION; IMMUNITY; SUBSETS; CD4(+)
AB The skin harbors a variety of resident leukocyte subsets that must be tightly regulated to maintain immune homeostasis. Hair follicles are unique structures in the skin that contribute to skin dendritic cell homeostasis through chemokine production. We demonstrate that CD4(+) and CD8(+) skin-resident memory T cells (T-RM cells), which are responsible for long-term skin immunity, reside predominantly within the hair follicle epithelium of the unperturbed epidermis. T-RM cell tropism for the epidermis and follicles is herein termed epidermotropism. Hair follicle expression of IL-15 was required for CD8(+) T-RM cells, and IL-7 for CD8(+) and CD4(+) T-RM cells, to exert epidermotropism. A lack of either cytokine in the skin led to impaired hapten-induced contact hypersensitivity responses. In a model of cutaneous T cell lymphoma, epidermotropic CD4(+) T-RM lymphoma cell localization depended on the presence of hair follicle-derived IL-7. These findings implicate hair follicle-derived cytokines as regulators of malignant and non-malignant T-RM cell tissue residence, and they suggest that the cytokines may be targeted therapeutically in inflammatory skin diseases and lymphoma.
C1 [Adachi, Takeya; Kobayashi, Tetsuro; Amagai, Masayuki; Nagao, Keisuke] Keio Univ, Sch Med, Dept Dermatol, Tokyo, Japan.
[Kobayashi, Tetsuro; Nagao, Keisuke] NCI, Dermatol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Sugihara, Eiji; Saya, Hideyuki] Keio Univ, Sch Med, Inst Adv Med Res, Div Gene Regulat, Tokyo, Japan.
[Yamada, Taketo] Keio Univ, Sch Med, Dept Pathol, Tokyo 160, Japan.
[Ikuta, Koichi] Kyoto Univ, Inst Virus Res, Dept Biol Responses, Lab Biol Protect, Kyoto 606, Japan.
[Pittaluga, Stefania] NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Nagao, K (reprint author), Keio Univ, Sch Med, Dept Dermatol, Tokyo, Japan.
EM keisuke.nagao@nih.gov
RI Amagai, Masayuki/K-5325-2013; Nagao, Keisuke/J-5116-2013
OI Amagai, Masayuki/0000-0003-3314-7052; Nagao, Keisuke/0000-0002-7005-3138
FU Japan Society for the Promotion of Science; Kanae Foundation for the
Promotion of Medical Science; Japanese Society for Investigative
Dermatology's (JSID's) Fellowship Shiseido Award; NIH NCI Intramural
Research Programs
FX We thank M. Ohyama for helpful discussion on human hair follicles; N.
Sakai, K. Eguchi and S. Sato (Keio University School of Medicine) for
their technical assistance; H. Kong (National Institutes of Health) for
their discussions on human CTCL; Y. Madokoro (Keio University School of
Medicine) for human CTCL immunohistochemical staining; T. Kitamura
(University of Tokyo) for providing the retroviral vector pMXs-IG and
Plat-E cells; J. Takeda (Osaka University) for providing K5-Cre mice;
D.H. Kaplan (University of Minnesota) for providing Langerin-DTA mice;
and B.E. Clausen (Johannes Gutenberg University of Mainz) for providing
Langerin-DTR mice. This work was supported by the Japan Society for the
Promotion of Science, The Kanae Foundation for the Promotion of Medical
Science, the Japanese Society for Investigative Dermatology's (JSID's)
Fellowship Shiseido Award and the NIH NCI Intramural Research Programs.
NR 33
TC 13
Z9 13
U1 1
U2 6
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1078-8956
EI 1546-170X
J9 NAT MED
JI Nat. Med.
PD NOV
PY 2015
VL 21
IS 11
BP 1272
EP 1279
DI 10.1038/nm.3962
PG 8
WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research &
Experimental
SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental
Medicine
GA CV9QH
UT WOS:000364621200011
PM 26479922
ER
PT J
AU Goedeke, L
Rotllan, N
Canfran-Duque, A
Aranda, JF
Ramirez, CM
Araldi, E
Lin, CS
Anderson, NN
Wagschal, A
de Cabo, R
Horton, JD
Lasuncion, MA
Naar, AM
Suarez, Y
Fernandez-Hernando, C
AF Goedeke, Leigh
Rotllan, Noemi
Canfran-Duque, Alberto
Aranda, Juan. F.
Ramirez, Cristina M.
Araldi, Elisa
Lin, Chin-Sheng
Anderson, Norma N.
Wagschal, Alexandre
de Cabo, Rafael
Horton, Jay D.
Lasuncion, Miguel A.
Naeaer, Anders M.
Suarez, Yajaira
Fernandez-Hernando, Carlos
TI MicroRNA-148a regulates LDL receptor and ABCA1 expression to control
circulating lipoprotein levels
SO NATURE MEDICINE
LA English
DT Article
ID LOW-DENSITY-LIPOPROTEIN; LEUCINE ZIPPER PROTEIN; CHOLESTEROL
HOMEOSTASIS; LIPID-METABOLISM; TRANSCRIPTION FACTOR; NONHUMAN-PRIMATES;
MESSENGER-RNAS; TARGET GENES; HUMAN GENOME; MICE
AB The hepatic low-density lipoprotein receptor (LDLR) pathway is essential for clearing circulating LDL cholesterol (LDL-C). Whereas the transcriptional regulation of LDLR is well characterized, the post-transcriptional mechanisms that govern LDLR expression are just beginning to emerge. Here we develop a high-throughput genome-wide screening assay to systematically identify microRNAs (miRNAs) that regulate LDLR activity in human hepatic cells. From this screen we identified and characterized miR-148a as a negative regulator of LDLR expression and activity and defined a sterol regulatory element binding protein 1 (SREBP1)-mediated pathway through which miR-148a regulates LDL-C uptake. In mice, inhibition of miR-148a increased hepatic LDLR expression and decreased plasma LDL-C. Moreover, we found that miR-148a regulates hepatic expression of ATP-binding cassette, subfamily A, member 1 (ABCA1) and circulating high-density lipoprotein cholesterol (HDL-C) levels in vivo. These studies uncover a role for miR-148a as a key regulator of hepatic LDL-C clearance through direct modulation of LDLR expression and demonstrate the therapeutic potential of inhibiting miR-148a to ameliorate an elevated LDL-C/HDL-C ratio, a prominent risk factor for cardiovascular disease.
C1 [Goedeke, Leigh; Rotllan, Noemi; Canfran-Duque, Alberto; Aranda, Juan. F.; Ramirez, Cristina M.; Araldi, Elisa; Suarez, Yajaira; Fernandez-Hernando, Carlos] Yale Univ, Sch Med, Vasc Biol & Therapeut Program, New Haven, CT 06520 USA.
[Goedeke, Leigh; Rotllan, Noemi; Canfran-Duque, Alberto; Aranda, Juan. F.; Ramirez, Cristina M.; Araldi, Elisa; Suarez, Yajaira; Fernandez-Hernando, Carlos] Yale Univ, Sch Med, Comparat Med Sect, Integrat Cell Signaling & Neurobiol Metab Program, New Haven, CT 06510 USA.
[Goedeke, Leigh; Aranda, Juan. F.; Araldi, Elisa; Lin, Chin-Sheng; Suarez, Yajaira; Fernandez-Hernando, Carlos] NYU, Sch Med, Dept Med, Leon H Charney Div Cardiol, New York, NY USA.
[Goedeke, Leigh; Araldi, Elisa; Lin, Chin-Sheng; Suarez, Yajaira; Fernandez-Hernando, Carlos] NYU, Sch Med, Dept Cell Biol, New York, NY 10016 USA.
[Anderson, Norma N.; Horton, Jay D.] Univ Texas SW Med Ctr Dallas, Dept Mol Genet, Dallas, TX 75390 USA.
[Anderson, Norma N.; Horton, Jay D.] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Dallas, TX 75390 USA.
[Wagschal, Alexandre; Naeaer, Anders M.] Massachusetts Gen Hosp, Ctr Canc, Charlestown, MA USA.
[Wagschal, Alexandre; Naeaer, Anders M.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA USA.
[de Cabo, Rafael] NIA, Translat Gerontol Branch, NIH, Baltimore, MD 21224 USA.
[Lasuncion, Miguel A.] Hosp Univ Ramon y Cajal, Serv Bioquim Invest, Inst Ramon y Cajal Invest Sanitaria, Madrid, Spain.
[Lasuncion, Miguel A.] Ctr Invest Biomed Red Fisiopatol Obesidad & Nutr, Madrid, Spain.
RP Fernandez-Hernando, C (reprint author), Yale Univ, Sch Med, Vasc Biol & Therapeut Program, New Haven, CT 06520 USA.
EM carlos.fernandez@yale.edu
RI Lasuncion, Miguel A./K-6167-2014; de Cabo, Rafael/J-5230-2016;
OI Lasuncion, Miguel A./0000-0003-0299-9391; de Cabo,
Rafael/0000-0002-3354-2442; Ramirez, Cristina M/0000-0003-2589-0786; ,
rafael/0000-0003-2830-5693
FU US National Institutes of Health (NIH) [R01HL107953, R01HL107953-04S1,
R01HL106063, R01HL105945, 1F31AG043318, P30KD034989]; American Heart
Association [15SDG23000025]; Howard Hughes Medical Institute
International Student Research Fellowship; Foundation Leducq
Transatlantic Network of Excellence in Cardiovascular Research;
Ministerio de Industria y Comercio, Spain [SAF2011-29951]; NIH, National
Institute of Aging; NIH [R01DK 094184, U24 DK059635]; Laura and Isaac
Perlmutter Cancer Center (NIH, National Cancer Institute grant)
[P30CA16087]; New York State Stem Cell Science (NYSTEM) [C026719]
FX We thank C. Yun, J. Recio, S. Katz and R. DasGupta at the New York
University (NYU) RNAi Core for their advice and assistance with the
miRNA screen, K. Harry and members of the Yale University Liver Center
for primary mouse hepatocyte isolation, members of the Iwakiri
laboratory for reagents and advice on primary hepatocyte culture, the
Yale University School of Medicine Mouse Metabolic Phenotyping Center
(MMPC) for liver toxicity measurements, P. Tontonoz (UCLA) for
generously providing the LDLR-GFP plasmid, the Nonhuman Primate Core of
the National Institute on Aging for providing liver samples and E.
Fisher (NYU School of Medicine) for kindly providing the human
hepatocellular carcinoma cell line (Huh7) and mouse hepatic cell line
(Hepal-6). This work was supported through grants by the US National
Institutes of Health (NIH; grants R01HL107953, R01HL107953-04S1 and
R01HL106063 (C.F.-H.); grant R01HL105945 (Y.S.); grant 1F31AG043318
(L.G.); grant P30KD034989 (Yale University Liver Center), the American
Heart Association (grant 15SDG23000025 (C.M.R.)), the Howard Hughes
Medical Institute International Student Research Fellowship (E.A.), the
Foundation Leducq Transatlantic Network of Excellence in Cardiovascular
Research (C.F.-H.) and the Ministerio de Industria y Comercio, Spain
(grant SAF2011-29951 (M.A.L.)). Centro de Investigacion Biomedica en Red
Fisiopatologia de Obesidad y Nutricion (CIBERobn) is an initiative of
Instituto de Salud Carlos III (ISCIII), Spain. R.d.C. is supported by
the Intramural Research Program of the NIH, National Institute of Aging.
A.M.N. and A.W. are supported by NIH grant R01DK 094184. The NYU RNAi
core is supported by the Laura and Isaac Perlmutter Cancer Center (NIH,
National Cancer Institute grant P30CA16087) and the New York State Stem
Cell Science (NYSTEM) contract C026719. The Yale University School of
Medicine MMPC is supported by NIH grant U24 DK059635.
NR 60
TC 25
Z9 25
U1 4
U2 13
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1078-8956
EI 1546-170X
J9 NAT MED
JI Nat. Med.
PD NOV
PY 2015
VL 21
IS 11
BP 1280
EP 1289
DI 10.1038/nm.3949
PG 10
WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research &
Experimental
SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental
Medicine
GA CV9QH
UT WOS:000364621200012
PM 26437365
ER
PT J
AU Wagschal, A
Najafi-Shoushtari, SH
Wang, L
Goedeke, L
Sinha, S
deLemos, AS
Black, JC
Ramirez, CM
Li, YX
Tewhey, R
Hatoum, I
Shah, N
Lu, Y
Kristo, F
Psychogios, N
Vrbanac, V
Lu, YC
Hla, T
de Cabo, R
Tsang, JS
Schadt, E
Sabeti, PC
Kathiresan, S
Cohen, DE
Whetstine, J
Chung, RT
Fernandez-Hernando, C
Kaplan, LM
Bernards, A
Gerszten, RE
Naar, AM
AF Wagschal, Alexandre
Najafi-Shoushtari, S. Hani
Wang, Lifeng
Goedeke, Leigh
Sinha, Sumita
deLemos, Andrew S.
Black, Josh C.
Ramirez, Cristina M.
Li, Yingxia
Tewhey, Ryan
Hatoum, Ida
Shah, Naisha
Lu, Yong
Kristo, Fjoralba
Psychogios, Nikolaos
Vrbanac, Vladimir
Lu, Yi-Chien
Hla, Timothy
de Cabo, Rafael
Tsang, John S.
Schadt, Eric
Sabeti, Pardis C.
Kathiresan, Sekar
Cohen, David E.
Whetstine, Johnathan
Chung, Raymond T.
Fernandez-Hernando, Carlos
Kaplan, Lee M.
Bernards, Andre
Gerszten, Robert E.
Naeaer, Anders M.
TI Genome-wide identification of microRNAs regulating cholesterol and
triglyceride homeostasis
SO NATURE MEDICINE
LA English
DT Article
ID CARDIOVASCULAR-DISEASE; ATHEROSCLEROSIS; HDL; MICE;
HYPERCHOLESTEROLEMIA; TRANSPORTERS; METABOLISM; MECHANISMS; RECEPTOR;
BINDING
AB Genome-wide association studies (GWASs) have linked genes to various pathological traits. However, the potential contribution of regulatory noncoding RNAs, such as microRNAs (miRNAs), to a genetic predisposition to pathological conditions has remained unclear. We leveraged GWAS meta-analysis data from >188,000 individuals to identify 69 miRNAs in physical proximity to single-nucleotide polymorphisms (SNPs) associated with abnormal levels of circulating lipids. Several of these miRNAs (miR-128-1, miR-148a, miR-130b, and miR-301b) control the expression of key proteins involved in cholesterol-lipoprotein trafficking, such as the low-density lipoprotein (LDL) receptor (LDLR) and the ATP-binding cassette A1 (ABCA1) cholesterol transporter. Consistent with human liver expression data and genetic links to abnormal blood lipid levels, overexpression and antisense targeting of miR-128-1 or miR-148a in high-fat diet-fed C57BL/6J and Apoe-null mice resulted in altered hepatic expression of proteins involved in lipid trafficking and metabolism, and in modulated levels of circulating lipoprotein-cholesterol and triglycerides. Taken together, these findings support the notion that altered expression of miRNAs may contribute to abnormal blood lipid levels, predisposing individuals to human cardiometabolic disorders.
C1 [Wagschal, Alexandre; Najafi-Shoushtari, S. Hani; Wang, Lifeng; Black, Josh C.; Kristo, Fjoralba; Whetstine, Johnathan; Bernards, Andre; Naeaer, Anders M.] Massachusetts Gen Hosp, Ctr Canc Res, Charlestown, MA 02129 USA.
[Wagschal, Alexandre; Najafi-Shoushtari, S. Hani; Wang, Lifeng; Naeaer, Anders M.] Harvard Univ, Sch Med, Dept Cell Biol, Boston, MA USA.
[Goedeke, Leigh; Ramirez, Cristina M.; Fernandez-Hernando, Carlos] Yale Univ, Sch Med, Dept Pathol, Comparat Med Sect, New Haven, CT 06510 USA.
[Sinha, Sumita; Psychogios, Nikolaos; Kathiresan, Sekar; Gerszten, Robert E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Res Ctr, Boston, MA USA.
[deLemos, Andrew S.; Chung, Raymond T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Liver, Boston, MA USA.
[deLemos, Andrew S.; Chung, Raymond T.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Div, Boston, MA USA.
[Black, Josh C.; Kathiresan, Sekar; Whetstine, Johnathan; Chung, Raymond T.; Kaplan, Lee M.; Bernards, Andre; Gerszten, Robert E.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Charlestown, MA USA.
[Li, Yingxia; Cohen, David E.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Div Gastroenterol, Boston, MA 02115 USA.
[Tewhey, Ryan; Sabeti, Pardis C.; Kathiresan, Sekar] MIT, Broad Inst, Cambridge, MA 02139 USA.
[Tewhey, Ryan; Sabeti, Pardis C.; Kathiresan, Sekar] Harvard, Cambridge, MA USA.
[Tewhey, Ryan; Sabeti, Pardis C.] Harvard Univ, Dept Organism & Evolutionary Biol, Cambridge, MA 02138 USA.
[Hatoum, Ida; Kaplan, Lee M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Obes Metab & Nutr Inst, Boston, MA USA.
[Hatoum, Ida; Kaplan, Lee M.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Gastrointestinal Unit, Boston, MA USA.
[Shah, Naisha; Lu, Yong; Tsang, John S.] NIAID, Syst Genom & Bioinformat Unit, Lab Syst Biol, NIH, Bethesda, MD 20892 USA.
[Vrbanac, Vladimir] Harvard Univ, Ctr AIDS Res, Cambridge, MA 02138 USA.
[Lu, Yi-Chien; Hla, Timothy] Cornell Univ, Weill Cornell Med Coll, Dept Pathol & Lab Med, Ctr Vasc Biol, New York, NY 10021 USA.
[de Cabo, Rafael] NIA, Expt Gerontol Sect, Translat Gerontol Branch, NIH, Baltimore, MD 21224 USA.
[Schadt, Eric] Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA.
[Kathiresan, Sekar; Bernards, Andre] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
RP Naar, AM (reprint author), Massachusetts Gen Hosp, Ctr Canc Res, Charlestown, MA 02129 USA.
EM naar@helix.mgh.harvard.edu
RI Black, Joshua/Q-2484-2015; de Cabo, Rafael/J-5230-2016; Hla,
Timothy/G-5873-2012;
OI de Cabo, Rafael/0000-0002-3354-2442; Kristo,
Fjoralba/0000-0002-8045-9756; Hla, Timothy/0000-0001-8355-4065; Ramirez,
Cristina M/0000-0003-2589-0786; , rafael/0000-0003-2830-5693
FU US National Institutes of Health (NIH) [R21DK084459, R01DK094184,
R37DK048873, R01DK056626, K24DK078772, R01HL107953, R01HL106063];
Massachusetts General Hospital (MGH); American Heart Association;
Fondation Leducq Transatlantic Network of Excellence in Cardiovascular
Research Award; NIH [R01HL49094]; US National Institute of Allergy and
Infectious Diseases; American Heart Association SDG Grant
[15SDG23000025]; MGH Executive Committee on Research; Neural Imaging
Center as part of a National Institutes on Neurological Disorders and
Stroke P30 Core Center grant [NS072030]; Harvard Digestive Diseases
Center [P30 DK034854]
FX This work was supported by the following grants: US National Institutes
of Health (NIH) grants R21DK084459 and R01DK094184 (A.M.N); R37DK048873
and R01DK056626 to D.E.C.; K24DK078772 to R.T.C.; and R01HL107953 and
R01HL106063 to C.F.-H. A.M.N. was supported by a scholar award from the
Massachusetts General Hospital (MGH). R.E.G. was supported by an
Established Investigator Award from the American Heart Association.
C.F.-H. was supported by a Fondation Leducq Transatlantic Network of
Excellence in Cardiovascular Research Award. T.H. acknowledges the
support of NIH grant R01HL49094 and a Fondation Leducq Transatlantic
Network of Excellence in Cardiovascular Research Award. N.S. and J.S.T.
were supported by the Intramural Research Program of the US National
Institute of Allergy and Infectious Diseases. C.M.R. was supported by
the American Heart Association SDG Grant 15SD G23000025. A.W. was
supported bye fellowship from the MGH Executive Committee on Research.
We thank C. Molony of Merck Research Laboratories for help with
genotyping data quality assessment. We thank the Harvard Medical School
Neurobiology Department and the Neurobiology Imaging Facility for
consultation and instrument availability that supported this work. This
facility is supported in part by the Neural Imaging Center as part of a
National Institutes on Neurological Disorders and Stroke P30 Core Center
grant no. NS072030, and by the Harvard Digestive Diseases Center (P30
DK034854).
NR 31
TC 30
Z9 30
U1 5
U2 22
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1078-8956
EI 1546-170X
J9 NAT MED
JI Nat. Med.
PD NOV
PY 2015
VL 21
IS 11
BP 1290
EP 1297
DI 10.1038/nm.3980
PG 8
WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research &
Experimental
SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental
Medicine
GA CV9QH
UT WOS:000364621200013
PM 26501192
ER
PT J
AU Bhiman, JN
Anthony, C
Doria-Rose, NA
Karimanzira, O
Schramm, CA
Khoza, T
Kitchin, D
Botha, G
Gorman, J
Garrett, NJ
Karim, SSA
Shapiro, L
Williamson, C
Kwong, PD
Mascola, JR
Morris, L
Moore, PL
AF Bhiman, Jinal N.
Anthony, Colin
Doria-Rose, Nicole A.
Karimanzira, Owen
Schramm, Chaim A.
Khoza, Thandeka
Kitchin, Dale
Botha, Gordon
Gorman, Jason
Garrett, Nigel J.
Karim, Salim S. Abdool
Shapiro, Lawrence
Williamson, Carolyn
Kwong, Peter D.
Mascola, John R.
Morris, Lynn
Moore, Penny L.
TI Viral variants that initiate and drive maturation of V1V2-directed HIV-1
broadly neutralizing antibodies
SO NATURE MEDICINE
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; B-CELL RECEPTORS; INFECTION; VACCINE;
PATHWAYS; ESCAPE; TARGET
AB The elicitation of broadly neutralizing antibodies (bNAbs) is likely to be essential for a preventative HIV-1 vaccine, but this has not yet been achieved by immunization. In contrast, some HIV-1-infected individuals naturally mount bNAb responses during chronic infection, suggesting that years of maturation may be required for neutralization breadth(1-6). Recent studies have shown that viral diversification precedes the emergence of bNAbs, but the significance of this observation is unknown(7,8). Here we delineate the key viral events that drove neutralization breadth within the CAP256-VRC26 family of 33 monoclonal antibodies (mAbs) isolated from a superinfected individual. First, we identified minority viral variants, termed bNAb-initiating envelopes, that were distinct from both of the transmitted/founder (T/F) viruses and that efficiently engaged the bNAb precursor. Second, deep sequencing revealed a pool of diverse epitope variants (immunotypes) that were preferentially neutralized by broader members of the antibody lineage. In contrast, a 'dead-end' antibody sublineage unable to neutralize these immunotypes showed limited evolution and failed to develop breadth. Thus, early viral escape at key antibody-virus contact sites selects for antibody sublineages 'that Can tolerate these changes, thereby providing a mechanism for the generation of neutralization breadth within a developing antibody lineage.
C1 [Bhiman, Jinal N.; Karimanzira, Owen; Khoza, Thandeka; Kitchin, Dale; Morris, Lynn; Moore, Penny L.] NICD, Ctr HIV & STIs, NHLS, Johannesburg, South Africa.
[Bhiman, Jinal N.; Morris, Lynn; Moore, Penny L.] Univ Witwatersrand, Fac Hlth Sci, Johannesburg, South Africa.
[Anthony, Colin; Botha, Gordon; Williamson, Carolyn] Univ Cape Town, Inst Infect Dis & Mol Med, ZA-7925 Cape Town, South Africa.
[Doria-Rose, Nicole A.; Gorman, Jason; Shapiro, Lawrence; Kwong, Peter D.; Mascola, John R.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Schramm, Chaim A.; Shapiro, Lawrence] Columbia Univ, Dept Biochem & Syst Biol, New York, NY USA.
[Garrett, Nigel J.; Karim, Salim S. Abdool; Williamson, Carolyn; Morris, Lynn; Moore, Penny L.] Univ KwaZulu Natal, Ctr AIDS Programme Res South Africa CAPRISA, Durban, South Africa.
[Williamson, Carolyn] Natl Hlth Lab Serv, Johannesburg, South Africa.
RP Moore, PL (reprint author), NICD, Ctr HIV & STIs, NHLS, Johannesburg, South Africa.
EM pennym@nicd.ac.za
OI Bhiman, Jinal/0000-0001-6354-4003; Moore, Penny/0000-0001-8719-4028; ,
Carolyn/0000-0003-0125-1226; , Lynn/0000-0003-3961-7828; Abdool Karim,
Salim/0000-0002-4986-2133
FU Centre for the AIDS Programme of Research (CAPRISA); South African
Medical Research Council (MRC) SHIP program; NIH [AI116086-01]; Vaccine
Research Center; National Institute of Allergy and Infectious Diseases
(NIAID); South African HIV/AIDS Research and Innovation Platform of the
South African Department of Science and Technology; US NIAID, NIH, US
Department of Health and Human Services grant [U19 AI51794]; Columbia
University-Southern African Fogarty AIDS International Training and
Research Program through the Fogarty International Center, NIH [5 D43
TW000231]; University of the Witwatersrand Postgraduate Merit Award;
Poliomyelitis Research Foundation PhD Bursary; National Research
Foundation of South Africa Innovation PhD Bursary; National Research
Foundation of South Africa; Wellcome Trust Intermediate Fellowship in
Public Health and Tropical Medicine [089933/Z/09/Z]
FX We thank the participants in the CAPRISA 002 cohort for their commitment
to attending the CAPRISA clinics in South Africa. Thanks to the CAPRISA
002 study team (including N. Naicker, V. Asari, N. Majola, T. Cekwane,
N. Samsunder, Z. Mchunu, D. Nkosi, H. Shozi, S. Ndlovu, P. Radebe, K.
Leask and M. Upfold) for managing the cohort and providing specimens. We
are grateful to C. K. Wibmer for useful discussions. We thank P.
Labuschagne, D. Matten and T. York for assistance with viral
next-generation sequence analysis, R. Bailer and M. Louder for the
CAP256-VRC26 UCA neutralization data against the large virus panel and
J. Mulllikin and the US National Institutes of Health (NIH) Intramural
Sequencing Center (NISC) Comparative Sequencing Program for antibody NGS
data at 34 weeks. We are grateful to J. Baalwa, D. Ellenberger, F. Gao,
B. Hahn, K. Hong, J. Kim, F. McCutchan, D. Montefiori, J. Overbaugh, E.
Sanders-Buell, G. Shaw, R. Swanstrom, M. Thomson, S. Tovanabutra and L.
Zhang for contributing the HIV-1 envelope plasmids used in our
neutralization panel. The JC53bl-13 (TZM-bl) and 293T cell lines were
obtained through the NIH AIDS Reagent Program, Division of AIDS, NIAID,
NIH from J.C. Kappes, X. Wu and Tranzyme, Inc., and A. Rice,
respectively. We acknowledge research funding from the Centre for the
AIDS Programme of Research (CAPRISA) (S.S.A.K.), the South African
Medical Research Council (MRC) SHIP program (P.L.M.), the NIH through a
U01 grant (AI116086-01) (P.L.M.), the intramural research programs of
the Vaccine Research Center and the National Institute of Allergy and
Infectious Diseases (NIAID) (J.R.M.). CAPRISA is funded by the South
African HIV/AIDS Research and Innovation Platform of the South African
Department of Science and Technology, and was initially supported by the
US NIAID, NIH, US Department of Health and Human Services grant U19
AI51794 (S.S.A.K.). Funding was received by J.N.B. and CA. from the
Columbia University-Southern African Fogarty AIDS International Training
and Research Program through the Fogarty International Center, NIH grant
5 D43 TW000231 (to Quarraisha Abdool Karim). Additional fellowships
included a University of the Witwatersrand Postgraduate Merit Award
(J.N.B.), a Poliomyelitis Research Foundation PhD Bursary (J.N.B.), a
National Research Foundation of South Africa Innovation PhD Bursary
(J.N.B.), a National Research Foundation of South Africa Postdoctoral
Fellowship (CA.), and a Wellcome Trust Intermediate Fellowship in Public
Health and Tropical Medicine, grant 089933/Z/09/Z (P.L.M.).
NR 26
TC 40
Z9 40
U1 0
U2 5
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1078-8956
EI 1546-170X
J9 NAT MED
JI Nat. Med.
PD NOV
PY 2015
VL 21
IS 11
BP 1332
EP 1336
DI 10.1038/nm.3963
PG 5
WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research &
Experimental
SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental
Medicine
GA CV9QH
UT WOS:000364621200018
PM 26457756
ER
PT J
AU Alam, MS
Gaida, MM
Bergmann, F
Lasitschka, F
Giese, T
Giese, NA
Hackert, T
Hinz, U
Hussain, SP
Kozlov, SV
Ashwell, JD
AF Alam, Muhammad S.
Gaida, Matthias M.
Bergmann, Frank
Lasitschka, Felix
Giese, Thomas
Giese, Nathalia A.
Hackert, Thilo
Hinz, Ulf
Hussain, S. Perwez
Kozlov, Serguei V.
Ashwell, Jonathan D.
TI Selective inhibition of the p38 alternative activation pathway in
infiltrating T cells inhibits pancreatic cancer progression
SO NATURE MEDICINE
LA English
DT Article
ID DUCTAL ADENOCARCINOMA; PROTEIN-KINASE; TUMOR-GROWTH; INFLAMMATION; MICE;
THERAPY; METASTASIS; PROGNOSIS; NEOPLASIA; CARCINOMA
AB Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive neoplasm characterized by a marked fibro-inflammatory microenvironment(1), the presence of which can promote both cancer induction and growth(2-4). Therefore, selective manipulation of local cytokines is an attractive, although unrealized, therapeutic approach. T cells possess a unique mechanism of p38 mitogen-activated protein kinase (MAPK) activation downstream of T cell receptor (TCR) engagement through the phosphorylation of Tyr323 (pY323). This alternative p38 activation pathway is required for pro-inflammatory cytokine production(5,6). Here we show in human PDAC that a high percentage of infiltrating pY323(+) T cells was associated with large numbers of tumor necrosis factor (TNF)-alpha- and interleukin (IL)-17-producing CD4(+) tumor-infiltrating lymphocytes (TILs) and aggressive disease. The growth of mouse pancreatic tumors was inhibited by genetic ablation of the alternative p38 pathway, and transfer of wild-type CD4(+) T cells, but not those lacking the alternative pathway, enhanced tumor growth in T cell-deficient mice. Notably, a plasma membrane-permeable peptide derived from GADD45-alpha, the naturally occurring inhibitor of p38 pY323(+) (ref. 7), reduced CD4(+) TIL production of INF-alpha, IL-17A, IL-10 and secondary cytokines, halted growth of implanted tumors and inhibited progression of spontaneous KRAS-driven adenocarcinoma in mice. Thus, TCR-mediated activation of CD4(+) TILs results in alternative p38 activation and production of protumorigenic factors and can be targeted for therapeutic benefit.
C1 [Alam, Muhammad S.; Gaida, Matthias M.; Ashwell, Jonathan D.] NCI, Lab Immune Cell Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Gaida, Matthias M.; Bergmann, Frank; Lasitschka, Felix] Univ Heidelberg Hosp, Inst Pathol, Heidelberg, Germany.
[Giese, Thomas] Heidelberg Univ, Inst Immunol, Heidelberg, Germany.
[Giese, Nathalia A.; Hackert, Thilo; Hinz, Ulf] Univ Heidelberg Hosp, Dept Surg, Heidelberg, Germany.
[Hussain, S. Perwez] NCI, Pancreat Canc Unit, Human Carcinogenesis Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
[Kozlov, Serguei V.] NCI, Canc & Dev Biol Lab, Ctr Canc Res, Frederick, MD 21701 USA.
RP Ashwell, JD (reprint author), NCI, Lab Immune Cell Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM jda@pop.nci.nih.gov
FU Intramural Research Program of the Center for Cancer Research, National
Cancer Institute, National Institutes of Health; German Research
Foundation (DFG) [Ga-1818/1-1]; German Research Foundation [SFB 938/TP
Z2]
FX We thank J. Scheuerer, M. Clauter, B. Walter and E. Castro for expert
technical assistance, J. Greiner for Panc02 cells, the Center for
Advanced Preclinical Research (CAPR) program at the Frederick National
Laboratory for Cancer Research for providing KPC mice for some studies,
T. Longerich and B. Lahrmann for technical advice in computer-based
tissue analysis and P. Schirmacher for critical review of the
manuscript. This work was supported by the Intramural Research Program
of the Center for Cancer Research, National Cancer Institute, National
Institutes of Health. M.M.G. was supported by a fellowship from the
German Research Foundation (DFG; Ga-1818/1-1). The work of F.L. was in
part funded by the German Research Foundation (grant no. SFB 938/TP Z2).
NR 34
TC 6
Z9 6
U1 2
U2 8
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1078-8956
EI 1546-170X
J9 NAT MED
JI Nat. Med.
PD NOV
PY 2015
VL 21
IS 11
BP 1337
EP 1343
DI 10.1038/nm.3957
PG 7
WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research &
Experimental
SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental
Medicine
GA CV9QH
UT WOS:000364621200019
PM 26479921
ER
PT J
AU Narayan, K
Subramaniam, S
AF Narayan, Kedar
Subramaniam, Sriram
TI Focused ion beams in biology
SO NATURE METHODS
LA English
DT Review
ID SCANNING-ELECTRON-MICROSCOPY; ATOM-PROBE TOMOGRAPHY; CRYOELECTRON
TOMOGRAPHY; CORRELATED LIGHT; IN-SITU; MAMMALIAN-CELLS; CELLULAR
ULTRASTRUCTURE; SPECIMEN PREPARATION; DENDRITIC CELLS; NEURAL CIRCUITS
AB A quiet revolution is under way in technologies used for nanoscale cellular imaging. Focused ion beams, previously restricted to the materials sciences and semiconductor fields, are rapidly becoming powerful tools for ultrastructural imaging of biological samples. Cell and tissue architecture, as preserved in plastic-embedded resin or in plunge-frozen form, can be investigated in three dimensions by scanning electron microscopy imaging of freshly created surfaces that result from the progressive removal of material using a focused ion beam. The focused ion beam can also be used as a sculpting tool to create specific specimen shapes such as lamellae or needles that can be analyzed further by transmission electron microscopy or by methods that probe chemical composition. Here we provide an in-depth primer to the application of focused ion beams in biology, including a guide to the practical aspects of using the technology, as well as selected examples of its contribution to the generation of new insights into subcellular architecture and mechanisms underlying host-pathogen interactions.
C1 [Narayan, Kedar; Subramaniam, Sriram] NCI, Ctr Mol Microscopy, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Narayan, Kedar] Frederick Natl Lab Canc Res, Canc Res Technol Program, Frederick, MD USA.
[Subramaniam, Sriram] NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Subramaniam, S (reprint author), NCI, Ctr Mol Microscopy, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM ss1@nih.gov
FU National Cancer Institute, US National Institutes of Health, Bethesda,
Maryland, USA
FX This work was supported by funds from the intramural program of the
National Cancer Institute, US National Institutes of Health, Bethesda,
Maryland, USA. The authors thank E. Tyler for artistic rendering of the
figures; E. He, A. Brust and D. Bliss for help creating Supplementary
Video 1 describing the FIB-SEM imaging process; and L. Earl and other
members of their laboratory for many fruitful discussions. The authors
apologize to those colleagues whose work has not been cited owing to
space constraints.
NR 109
TC 6
Z9 6
U1 10
U2 46
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1548-7091
EI 1548-7105
J9 NAT METHODS
JI Nat. Methods
PD NOV
PY 2015
VL 12
IS 11
BP 1021
EP 1031
DI 10.1038/NMETH.3623
PG 11
WC Biochemical Research Methods
SC Biochemistry & Molecular Biology
GA CV8BG
UT WOS:000364500900015
PM 26513553
ER
PT J
AU Makarova, KS
Wolf, YI
Alkhnbashi, OS
Costa, F
Shah, SA
Saunders, SJ
Barrangou, R
Brouns, SJJ
Charpentier, E
Haft, DH
Horvath, P
Moineau, S
Mojica, FJM
Terns, RM
Terns, MP
White, MF
Yakunin, AF
Garrett, RA
van der Oost, J
Backofen, R
Koonin, EV
AF Makarova, Kira S.
Wolf, Yuri I.
Alkhnbashi, Omer S.
Costa, Fabrizio
Shah, Shiraz A.
Saunders, Sita J.
Barrangou, Rodolphe
Brouns, Stan J. J.
Charpentier, Emmanuelle
Haft, Daniel H.
Horvath, Philippe
Moineau, Sylvain
Mojica, Francisco J. M.
Terns, Rebecca M.
Terns, Michael P.
White, Malcolm F.
Yakunin, Alexander F.
Garrett, Roger A.
van der Oost, John
Backofen, Rolf
Koonin, Eugene V.
TI An updated evolutionary classification of CRISPR-Cas systems
SO NATURE REVIEWS MICROBIOLOGY
LA English
DT Article
ID SHORT PALINDROMIC REPEATS; RNA-SILENCING COMPLEX; GUIDED SURVEILLANCE
COMPLEX; BACTERIAL IMMUNE-SYSTEM; DNA-REPAIR SYSTEM; ADAPTIVE IMMUNITY;
CRYSTAL-STRUCTURE; STREPTOCOCCUS-THERMOPHILUS; ESCHERICHIA-COLI; DEFENSE
SYSTEMS
AB The evolution of CRISPR-cas loci, which encode adaptive immune systems in archaea and bacteria, involves rapid changes, in particular numerous rearrangements of the locus architecture and horizontal transfer of complete loci or individual modules. These dynamics complicate straightforward phylogenetic classification, but here we present an approach combining the analysis of signature protein families and features of the architecture of cas loci that unambiguously partitions most CRISPR-cas loci into distinct classes, types and subtypes. The new classification retains the overall structure of the previous version but is expanded to now encompass two classes, five types and 16 subtypes. The relative stability of the classification suggests that the most prevalent variants of CRISPR-Cas systems are already known. However, the existence of rare, currently unclassifiable variants implies that additional types and subtypes remain to be characterized.
C1 [Makarova, Kira S.; Wolf, Yuri I.; Haft, Daniel H.; Koonin, Eugene V.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
[Alkhnbashi, Omer S.; Costa, Fabrizio; Saunders, Sita J.; Backofen, Rolf] Univ Freiburg, Bioinformat Grp, Dept Comp Sci, D-79110 Freiburg, Germany.
[Shah, Shiraz A.; Garrett, Roger A.] Univ Copenhagen, Archaea Ctr, Dept Biol, DK-2200 Copenhagen N, Denmark.
[Barrangou, Rodolphe] N Carolina State Univ, Dept Food Bioproc & Nutr Sci, Raleigh, NC 27606 USA.
[Brouns, Stan J. J.; van der Oost, John] Wageningen Univ, Microbiol Lab, NL-6703 HB Wageningen, Netherlands.
[Charpentier, Emmanuelle] Helmholtz Ctr Infect Res, Dept Regulat Infect Biol, D-38124 Braunschweig, Germany.
[Horvath, Philippe] DuPont Nutr & Hlth, F-86220 Dange St Romain, France.
[Moineau, Sylvain] Univ Laval, Dept Biochim Microbiol & Bioinformat, Felix Herelle Reference Ctr Bacterial Viruses, Fac Sci & Genie,Grp Rech Ecol Buccale,Fac Med Den, Quebec City, PQ, Canada.
[Mojica, Francisco J. M.] Univ Alicante, Dept Fisiol Genet & Microbiol, E-03080 Alicante, Spain.
[Terns, Rebecca M.; Terns, Michael P.] Univ Georgia, Biochem & Mol Biol, Genet & Microbiol, Athens, GA 30602 USA.
[White, Malcolm F.] Univ St Andrews, St Andrews KY16 9TZ, Fife, Scotland.
[Yakunin, Alexander F.] Univ Toronto, Dept Chem Engn & Appl Chem, Toronto, ON M5S 3E5, Canada.
[Backofen, Rolf] Univ Freiburg, BIOSS Ctr Biol Signaling Studies, Cluster Excellence, Freiburg, Germany.
RP Koonin, EV (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
EM koonin@ncbl.nlm.nih.gov
RI Barrangou, Rodolphe/I-2878-2014; Mojica, Francisco/K-2414-2014; Shah,
Shiraz/M-5132-2016; Terns, Michael/N-6435-2016; Garrett,
Roger/M-2450-2014; HORVATH, Philippe/K-5266-2015;
OI Barrangou, Rodolphe/0000-0002-0648-3504; Mojica,
Francisco/0000-0002-6660-4996; Shah, Shiraz/0000-0002-4665-577X;
HORVATH, Philippe/0000-0003-2015-8123; White,
Malcolm/0000-0003-1543-9342; Yakunin, Alexander/0000-0003-0813-6490;
Costa, Fabrizio/0000-0002-4900-995X
FU National Institutes of Health (NIH) Intramural Research Program at the
National Library of Medicine, US Department of Health and Human
Services; NIH [RO1 GM54682, RO1 GM99876]; SIAM Gravitation Grant from
the Netherlands Organization for Scientific Research [024.002.002]; NWO
Vidi grant [864.11.005]; European Research Council (ERC) Stg [639707];
Natural Sciences and Engineering Research Council (NSERC) Strategic
Network Grant IBN; NSERC Discovery grant; Natural Sciences and
Engineering Research Council of Canada (Discovery program); Ministerio
de Economia y Competitividad [B102014-53029]; Deutsche
Forschungsgemeinschaft (DFG) [BA 2168/5-2]; Danish Natural Science
Research Council
FX K.S.M., Y.I.W., D.H. and E.V.K. are supported by the National Institutes
of Health (NIH) Intramural Research Program at the National Library of
Medicine, US Department of Health and Human Services. R.M.T. and M.P.T.
are supported by NIH grants RO1 GM54682 and RO1 GM99876. J.v.d.O. was
partly supported by SIAM Gravitation Grant 024.002.002 from the
Netherlands Organization for Scientific Research (N.W.O.). S.J.J.B. was
financially supported by an NWO Vidi grant (864.11.005) and European
Research Council (ERC) Stg (639707). A.F.Y. is supported by the Natural
Sciences and Engineering Research Council (NSERC) Strategic Network
Grant IBN and NSERC Discovery grant. S.M. acknowledges funding from
Natural Sciences and Engineering Research Council of Canada (Discovery
program) and holds a Tier 1 Canada Research Chair in Bacteriophages.
F.J.M.M. is supported by the Ministerio de Economia y Competitividad
(B102014-53029). R.B. is supported by the Deutsche
Forschungsgemeinschaft (DFG) grant (BA 2168/5-2). S.A.S. and R.A.G. were
funded primarily by the Danish Natural Science Research Council. O.S.A.,
F C., S.J.S., R.B., S.A.S and R A.G. are grateful to all members of the
FOR1680 for helpful discussions.
NR 117
TC 190
Z9 195
U1 49
U2 155
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1740-1526
EI 1740-1534
J9 NAT REV MICROBIOL
JI Nat. Rev. Microbiol.
PD NOV
PY 2015
VL 13
IS 11
BP 722
EP 736
DI 10.1038/nrmicro3569
PG 15
WC Microbiology
SC Microbiology
GA CV9QE
UT WOS:000364620900009
PM 26411297
ER
PT J
AU Kiage, JN
Sampson, UKA
Lipworth, L
Fazio, S
Mensah, GA
Yu, Q
Munro, H
Akwo, EA
Dai, Q
Blot, WJ
Kabagambe, EK
AF Kiage, J. N.
Sampson, U. K. A.
Lipworth, L.
Fazio, S.
Mensah, G. A.
Yu, Q.
Munro, H.
Akwo, E. A.
Dai, Q.
Blot, W. J.
Kabagambe, E. K.
TI Intake of polyunsaturated fat in relation to mortality among statin
users and non-users in the Southern Community Cohort Study
SO NUTRITION METABOLISM AND CARDIOVASCULAR DISEASES
LA English
DT Article
DE PUFA; Fish; Hypertension; Mortality; Cardiovascular disease; Prospective
ID REDUCE BLOOD-PRESSURE; STROKE REGARDS COHORT; CARDIOVASCULAR-DISEASE;
MYOCARDIAL-INFARCTION; RACIAL-DIFFERENCES; RISK-FACTORS; TRANS FAT;
FISH-OIL; ACIDS; HYPERTENSION
AB Background and aims: Consumption of polyunsaturated fatty acids (PUFA), especially the n3-series, may protect against cardiovascular disease (CVD), but recent randomized studies have failed to demonstrate these benefits. One of the prevailing hypotheses is that PUFA intake may not confer benefits beyond those provided by statins, but studies comparing statin users to non-users with regard to effects of PUFA are lacking.
Methods and results: Black and white men and women (n = 69,559) in the Southern Community Cohort Study were studied. Cox regression models adjusting for age, sex, race, BMI, recruitment site, education, income, smoking, diabetes, and dietary variables were used.
Results: At baseline the mean +/- SD age was 52 +/- 9 years, 60% of participants were women, 54% had hypertension and 16% used statins. We observed modest inverse associations between n3-PUFA and n6-PUFA intake with mortality among non-statin users but not among statin users. In adjusted analyses, the HRs (95% CIs) for all-cause mortality (6,396 deaths over a median of 6.4 years) comparing the highest to the lowest quintile were 0.90 (0.82-1.00) for n3-PUFA and 0.80 (0.70-0.92) for n6-PUFA among non-statin users, whereas they were 1.06 (0.87-1.28) and 0.96 (0.78-1.19) for n3-PUFA and n6-PUFA, respectively, among statin users.
Conclusions: Our results suggest potential benefits of PUFA consumption on mortality which are only apparent in the absence of statin therapy. It seems prudent to consider the potential benefit of PUFA consumption in the primary prevention of CVD among patients who are not candidates for statin therapy but are at increased risk for CVD and mortality. (C) 2015 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.
C1 [Kiage, J. N.; Lipworth, L.; Akwo, E. A.; Dai, Q.; Blot, W. J.; Kabagambe, E. K.] Vanderbilt Univ, Div Epidemiol, Dept Med, Med Ctr, Nashville, TN 37203 USA.
[Sampson, U. K. A.; Mensah, G. A.] NHLBI, CTRIS, Bethesda, MD USA.
[Lipworth, L.; Akwo, E. A.; Kabagambe, E. K.] Vanderbilt Univ, Vanderbilt Ctr Translat & Clin Cardiovasc Res, Med Ctr, Nashville, TN 37203 USA.
[Fazio, S.] Oregon Hlth & Sci Univ, Knight Cardiovasc Inst, Ctr Prevent Cardiol, Portland, OR 97239 USA.
[Yu, Q.] Westat Corp, Rockville, MD 20850 USA.
[Munro, H.; Blot, W. J.] Int Epidemiol Inst, Rockville, MD 20850 USA.
RP Kabagambe, EK (reprint author), Vanderbilt Univ, Div Epidemiol, Dept Med, Nashville, TN 37203 USA.
EM kiagejn@gmail.com; uchechukwu.sampson@nih.gov; lipworth@vanderbilt.edu;
fazio@ohsu.edu; george.mensah@nih.gov; qiluyu@westat.com;
heather@iei.us; elvis.a.akwo@vanderbilt.edu; qi.dai@vanderbilt.edu;
william.j.blot@vanderbilt.edu; edmond.kabagambe@vanderbilt.edu
FU National Cancer Institute [R01 CA092447]; American Recovery and
Reinvestment Act [3R01 CA092447-08S1]; PepsiCo Global Research and
Development
FX This study was primarily supported by a grant from the National Cancer
Institute (R01 CA092447) and funds from the American Recovery and
Reinvestment Act (3R01 CA092447-08S1). Additional funding for this study
was provided by PepsiCo Global Research and Development.
NR 42
TC 3
Z9 3
U1 2
U2 8
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0939-4753
EI 1590-3729
J9 NUTR METAB CARDIOVAS
JI Nutr. Metab. Carbiovasc. Dis.
PD NOV
PY 2015
VL 25
IS 11
BP 1016
EP 1024
DI 10.1016/j.numecd.2015.07.006
PG 9
WC Cardiac & Cardiovascular Systems; Endocrinology & Metabolism; Nutrition
& Dietetics
SC Cardiovascular System & Cardiology; Endocrinology & Metabolism;
Nutrition & Dietetics
GA CV7EA
UT WOS:000364434000005
PM 26298428
ER
PT J
AU Reynolds, CP
Kang, MH
Maris, JM
Kolb, EA
Gorlick, R
Wu, JR
Kurmasheva, RT
Houghton, PJ
Smith, MA
AF Reynolds, C. Patrick
Kang, Min H.
Maris, John M.
Kolb, E. Anders
Gorlick, Richard
Wu, Jianrong
Kurmasheva, Raushan T.
Houghton, Peter J.
Smith, Malcolm A.
TI Initial Testing (Stage 1) of the Anti-Microtubule Agents Cabazitaxel and
Docetaxel, by the Pediatric Preclinical Testing Program
SO PEDIATRIC BLOOD & CANCER
LA English
DT Article
DE developmental therapeutics; preclinical testing; taxane derivatives
ID CHILDRENS-ONCOLOGY-GROUP; SOLID TUMORS; PHASE-II; PROSTATE-CANCER; BONE
SARCOMA; BRAIN-TUMORS; PACLITAXEL; TAXANES; MODELS; GEMCITABINE
AB Background. Although microtubule-destabilizing agents (principally vincristine) are in common use in pediatric oncology, the microtubule-stabilizing taxanes are uncommonly used to treat childhood cancers. Cabazitaxel has been reported to have activity superior to that of docetaxel in preclinical models of multidrug resistant adult cancers, and it was active in patients who had progressed on or after docetaxel. The PPTP conducted a comparison of these two agents against the PPTP in vitro panel and against a limited panel of solid tumor xenografts. Procedures. Cabazitaxel and docetaxel were tested against the PPTP in vitro cell line panel at concentrations from 0.01nM to 0.1 mu M and in vivo against a subset of the PPTP solid tumor xenograft models at a dose of 10 or 7.5 mg/kg on an every 4 days x 3 I. V. schedule. Results. In vitro, both cabazitaxel and docetaxel had similar potency (median rIC(50) 0.47nM and 0.88 nM, respectively) and a similar activity profile, with Ewing sarcoma cells being significantly more sensitive to both agents. In vitro sensitivity to docetaxel inversely correlated with mRNA expression for ABCB1, but the correlation with ABCB1 expression was weaker for cabazitaxel. In vivo cabazitaxel demonstrated significantly greater activity than docetaxel in five of 12 tumor models, inducing regressions in six models compared with three models for docetaxel. Conclusions. Cabazitaxel demonstrated superior activity compared to docetaxel. The lower cabazitaxel systemic exposure tolerated in humans compared to mice needs to be considered when extrapolating these results to the clinical setting. Pediatr Blood Cancer (C) 2015 Wiley Periodicals, Inc. 2015; 62:1897-1905. (C) 2015 Wiley Periodicals, Inc.
C1 [Reynolds, C. Patrick; Kang, Min H.] Texas Tech Univ, Hlth Sci Ctr, Lubbock, TX 79430 USA.
[Maris, John M.] Univ Penn, Childrens Hosp Philadelphia, Sch Med, Philadelphia, PA 19104 USA.
[Maris, John M.] Abramson Family Canc Res Inst, Philadelphia, PA USA.
[Kolb, E. Anders] Alfred I DuPont Hosp Children, Wilmington, DE USA.
[Gorlick, Richard] Childrens Hosp Montefiore, Bronx, NY USA.
[Wu, Jianrong] St Jude Childrens Res Hosp, Memphis, TN 38105 USA.
[Kurmasheva, Raushan T.; Houghton, Peter J.] Nationwide Childrens Hosp, Columbus, OH USA.
[Smith, Malcolm A.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
RP Reynolds, CP (reprint author), Texas Tech Univ, Hlth Sci Ctr, 3601 4th St STOP 9445, Lubbock, TX 79430 USA.
EM Patrick.Reynolds@TTUHSC.edu
OI Reynolds, C. Patrick/0000-0002-2827-8536
FU NCI NIH HHS [CA21765, N01-CM-42216, N01CM42216, P01 CA023099, P30
CA013330, P30 CA021765, P50 CA108786, CA108786]
NR 25
TC 4
Z9 4
U1 0
U2 1
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 NOV
PY 2015
VL 62
IS 11
BP 1897
EP 1905
DI 10.1002/pbc.25611
PG 9
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA CV9BA
UT WOS:000364581100006
PM 26154614
ER
PT J
AU Gu, QP
Dillon, CF
Eberhardt, MS
Wright, JD
Burt, VL
AF Gu, Qiuping
Dillon, Charles F.
Eberhardt, Mark S.
Wright, Jacqueline D.
Burt, Vicki L.
TI Preventive Aspirin and Other Antiplatelet Medication Use Among US Adults
Aged >= 40 Years: Data from the National Health and Nutrition
Examination Survey, 2011-2012
SO PUBLIC HEALTH REPORTS
LA English
DT Article
ID AMERICAN-HEART-ASSOCIATION; OF-CARDIOLOGY FOUNDATION; EXPERT CONSENSUS
DOCUMENT; LOW-DOSE ASPIRIN; CARDIOVASCULAR-DISEASE; TASK-FORCE;
MYOCARDIAL-INFARCTION; DIABETES-ASSOCIATION; SECONDARY PREVENTION;
SCIENTIFIC STATEMENT
AB Objective. We estimated the prevalence of preventive aspirin and/or other antiplatelet medication use and the dosage of aspirin use in the U.S. adult population.
Methods. We conducted cross-sectional analyses of a representative sample (n=3,599) of U.S. adults aged >= 40 years from the National Health and Nutrition Examination Survey, 2011-2012.
Results. In 2011-2012, one-third of U.S. adults aged >= 40 years reported taking preventive aspirin and/or other antiplatelet medications, 97% of whom indicated preventive aspirin use. Preventive aspirin use increased with age (from 11% of those aged 40-49 years to 54% of those >= 80 years of age, p<0.001). Non-Hispanic white (35%) and black (30%) adults were more likely to take preventive aspirin than non-Hispanic Asian (20%, p<0.001) and Hispanic (22%, p=0.013) adults. Adults with, compared with those without health insurance, and adults with >= 2 doctor visits in the past year, diagnosed diabetes, hypertension, or high cholesterol were twice as likely to take preventive aspirin. Among those with cardiovascular disease, 76% reported taking preventive aspirin and/or other antiplatelet medications, of whom 91% were taking preventive aspirin. Among adults without cardiovascular disease, 28% reported taking preventive aspirin. Adherence rates to medically recommended aspirin use were 82% overall, 91% for secondary prevention, and 79% for primary prevention. Among current preventive aspirin users, 70% were taking 81 milligrams (mg) of aspirin daily and 13% were taking 325 mg of aspirin daily.
Conclusion. The vast majority of antiplatelet therapy is preventive aspirin use. A health-care provider's recommendation to take preventive aspirin is an important determinant of current preventive aspirin use.
C1 [Gu, Qiuping; Dillon, Charles F.; Eberhardt, Mark S.; Burt, Vicki L.] Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Div Hlth & Nutr Examinat Surveys, Hyattsville, MD 20782 USA.
[Wright, Jacqueline D.] NHLBI, NIH, Bethesda, MD 20892 USA.
RP Gu, QP (reprint author), Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Div Hlth & Nutr Examinat Surveys, 3311 Toledo Rd, Hyattsville, MD 20782 USA.
EM qag3@cdc.gov
NR 39
TC 0
Z9 0
U1 2
U2 6
PU ASSOC SCHOOLS PUBLIC HEALTH
PI WASHINGTON
PA 1900 M ST NW, STE 710, WASHINGTON, DC 20036 USA
SN 0033-3549
J9 PUBLIC HEALTH REP
JI Public Health Rep.
PD NOV-DEC
PY 2015
VL 130
IS 6
BP 643
EP 654
PG 12
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA CV8CI
UT WOS:000364503700013
PM 26556936
ER
PT J
AU Culty, M
Liu, Y
Manku, G
Chan, WY
Papadopoulos, V
AF Culty, Martine
Liu, Ying
Manku, Gurpreet
Chan, Wai-Yee
Papadopoulos, Vassilios
TI Expression of steroidogenesis-related genes in murine male germ cells
SO STEROIDS
LA English
DT Article
DE Testis; Germ cells; Steroidogenesis; Spermatogenesis
ID 18 KDA TSPO; TRANSLOCATOR PROTEIN; LEYDIG-CELLS; SEMINIFEROUS
EPITHELIUM; ESTROGEN-RECEPTORS; STEROID-HORMONES; GROWTH-FACTOR; START
DOMAIN; RAT TESTIS; IN-VITRO
AB For decades, only few tissues and cell types were defined as steroidogenic, capable of de novo steroid synthesis from cholesterol. However, with the refinement of detection methods, several tissues have now been added to the list of steroidogenic tissues. Besides their critical role as long-range acting hormones, steroids are also playing more discreet roles as local mediators and signaling molecules within the tissues they are produced. In testis, steroidogenesis is carried out by the Leydig cells through a broad network of proteins, mediating cholesterol delivery to CYP11A1, the first cytochrome of the steroidogenic cascade, and the sequential action of enzymes insuring the production of active steroids, the main one being testosterone. The knowledge that male germ cells can be directly regulated by steroids and that they express several steroidogenesis-related proteins led us to hypothesize that germ cells could produce steroids, acting as autocrine, intracrine and juxtacrine modulators, as a way to insure synchronized progression within spermatogenic cycles, and preventing inappropriate cell behaviors between neighboring cells. Gene expression and protein analyses of mouse and rat germ cells from neonatal gonocytes to spermatozoa showed that most steroidogenesis-associated genes are expressed in germ cells, showing cell type-, spermatogenic cycle-, and age-specific expression profiles. Highly expressed genes included genes involved in steroidogenesis and other cell functions, such as Acbd1 and 3, Tspo and Vdac1-3, and genes involved in fatty acids metabolism or synthesis, including Hsb17b4 10 and 12, implying broader roles than steroid synthesis in germ cells. These results support the possibility of an additional level of regulation of spermatogenesis exerted between adjacent germ cells. (C) 2015 Elsevier Inc. All rights reserved.
C1 [Culty, Martine; Manku, Gurpreet; Papadopoulos, Vassilios] McGill Univ, Res Inst, Ctr Hlth, Montreal, PQ H4A 3J1, Canada.
[Culty, Martine; Manku, Gurpreet; Papadopoulos, Vassilios] McGill Univ, Dept Med, Montreal, PQ H4A 3J1, Canada.
[Culty, Martine; Manku, Gurpreet; Papadopoulos, Vassilios] McGill Univ, Dept Pharmacol & Therapeut, Montreal, PQ H4A 3J1, Canada.
[Liu, Ying] NHLBI, Sect Expt Atherosclerosis, Ctr Mol Med, NIH, Bethesda, MD 20892 USA.
[Chan, Wai-Yee] Chinese Univ Hong Kong, Fac Med, Sch Biomed Sci, Hong Kong, Hong Kong, Peoples R China.
RP Culty, M (reprint author), McGill Univ, Res Inst, Ctr Hlth, 1001 Decarie Blvd,Bloc E,Room EM1-3218, Montreal, PQ H4A 3J1, Canada.
EM martine.culty@mcgill.ca
OI Papadopoulos, Vassilios/0000-0002-1183-8568
FU Natural Sciences and Engineering Research Council of Canada (NSERC)
[386038-2013]; Canadian Institutes of Health Research (CIHR) Operating
Grant [MOP-102647]; Canada Research Chair; Division of Endocrinology and
Metabolism of the MUHC; Reseau Quebecois en Reproduction (RQR); Center
Grant from Le Fonds de la Recherche en Sante du Quebec (FRSQ)
FX We are thankful to Dr. Jaroslav Novak for his assistance with the
statistical analysis of the gene expression arrays. This work was
supported in part by a Discovery Grant from the Natural Sciences and
Engineering Research Council of Canada (NSERC) (No. 386038-2013) to
M.C.; a Canadian Institutes of Health Research (CIHR) Operating Grant
(No. MOP-102647) and a Canada Research Chair to V.P.; and scholarship
awards from the Division of Endocrinology and Metabolism of the MUHC and
the Reseau Quebecois en Reproduction (RQR) to G.M. The Research
Institute of the MUHC is supported in part by a Center Grant from Le
Fonds de la Recherche en Sante du Quebec (FRSQ).
NR 59
TC 2
Z9 2
U1 0
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0039-128X
EI 1878-5867
J9 STEROIDS
JI Steroids
PD NOV
PY 2015
VL 103
SI SI
BP 105
EP 114
DI 10.1016/j.steroids.2015.08.011
PG 10
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA CV9LB
UT WOS:000364607600011
PM 26302977
ER
PT J
AU Insel, T
AF Insel, Thomas
TI The Treatment Gap
SO TECHNOLOGY REVIEW
LA English
DT Editorial Material
C1 NIMH, Washington, DC 20892 USA.
RP Insel, T (reprint author), NIMH, Washington, DC 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU TECHNOL REV
PI CAMBRIDGE
PA 1 MAIN ST, 13 FLR, CAMBRIDGE, MA 02142 USA
SN 1099-274X
J9 TECHNOL REV
JI Technol. Rev.
PD NOV-DEC
PY 2015
VL 118
IS 6
BP 13
EP 13
PG 1
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CV9QL
UT WOS:000364621600015
ER
PT J
AU Taraska, JW
AF Taraska, Justin W.
TI SIMply Better Resolution in Live Cells
SO TRENDS IN CELL BIOLOGY
LA English
DT Editorial Material
ID STRUCTURED-ILLUMINATION MICROSCOPY; FLUORESCENCE MICROSCOPY; EXCITATION
MICROSCOPY; IMPROVEMENT
C1 NHLBI, Biochem & Biophys Ctr, NIH, Bethesda, MD 20824 USA.
RP Taraska, JW (reprint author), NHLBI, Biochem & Biophys Ctr, NIH, 50 South Dr,Bldg 50, Bethesda, MD 20824 USA.
EM justin.taraska@nih.gov
RI Taraska, Justin/H-8876-2016
OI Taraska, Justin/0000-0001-5355-9535
FU Intramural NIH HHS [ZIA HL006098-05, Z99 HL999999]
NR 10
TC 0
Z9 0
U1 0
U2 5
PU ELSEVIER SCIENCE LONDON
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0962-8924
J9 TRENDS CELL BIOL
JI Trends Cell Biol.
PD NOV
PY 2015
VL 25
IS 11
BP 636
EP 638
DI 10.1016/j.tcb.2015.09.007
PG 3
WC Cell Biology
SC Cell Biology
GA CV9LI
UT WOS:000364608300003
PM 26458328
ER
PT J
AU Petrie, RJ
Yamada, KM
AF Petrie, Ryan J.
Yamada, Kenneth M.
TI Fibroblasts Lead the Way: A Unified View of 3D Cell Motility
SO TRENDS IN CELL BIOLOGY
LA English
DT Review
ID INTERMEDIATE-FILAMENTS; MIGRATING CELLS; FORCE TRANSMISSION; ADHESION
DYNAMICS; STRESS FIBERS; LIVING CELLS; MYOSIN IIB; MATRIX;
CONTRACTILITY; ACTIVATION
AB Primary human fibroblasts are remarkably adaptable, able to migrate in differing types of physiological 3D tissue and on rigid 2D tissue culture surfaces. The crawling behavior of these and other vertebrate cells has been studied intensively, which has helped generate the concept of the cell motility cycle as a comprehensive model of 2D cell migration. However, this model fails to explain how cells force their large nuclei through the confines of a 3D matrix environment and why primary fibroblasts can use more than one mechanism to move in 3D. Recent work shows that the intracellular localization of myosin II activity is governed by cell-matrix interactions to both force the nucleus through the extracellular matrix (ECM) and dictate the type of protrusions used to migrate in 3D.
C1 [Petrie, Ryan J.; Yamada, Kenneth M.] Natl Inst Dent & Craniofacial Res, Lab Cell & Dev Biol, NIH, Bethesda, MD 20892 USA.
RP Petrie, RJ (reprint author), Natl Inst Dent & Craniofacial Res, Lab Cell & Dev Biol, NIH, Bethesda, MD 20892 USA.
EM petrier@mail.nih.gov; kyamada@mail.nlh.gov
FU Intramural Research Program of the National Institutes of Health,
National Institute of Dental and Craniofacial Research (NIH, NIDCR)
FX We thank C. Parent, A. Doyle, W. Daley, and M. Hague for their critical
comments and suggestions on the manuscript. Work in the authors'
laboratory is supported by the Intramural Research Program of the
National Institutes of Health, National Institute of Dental and
Craniofacial Research (NIH, NIDCR).
NR 69
TC 8
Z9 8
U1 5
U2 20
PU ELSEVIER SCIENCE LONDON
PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0962-8924
J9 TRENDS CELL BIOL
JI Trends Cell Biol.
PD NOV
PY 2015
VL 25
IS 11
BP 666
EP 674
DI 10.1016/j.tcb.2015.07.013
PG 9
WC Cell Biology
SC Cell Biology
GA CV9LI
UT WOS:000364608300006
PM 26437597
ER
PT J
AU Traslavina, RP
Reilly, CM
Vasireddy, R
Samitz, EM
Stepnik, CT
Outerbridge, C
Affolter, VK
Byrne, BA
Lowenstine, LJ
White, SD
Murphy, B
AF Traslavina, R. P.
Reilly, C. M.
Vasireddy, R.
Samitz, E. M.
Stepnik, C. T.
Outerbridge, C.
Affolter, V. K.
Byrne, B. A.
Lowenstine, L. J.
White, S. D.
Murphy, B.
TI Laser Capture Microdissection of Feline Streptomyces spp
Pyogranulomatous Dermatitis and Cellulitis
SO VETERINARY PATHOLOGY
LA English
DT Article
DE cats; Streptomyces; Actinomycetales; dermatitis; cellulitis; laser
capture microdissection; mycetoma
ID ACTINOMYCOTIC MYCETOMA
AB Suspected Streptomyces spp infections were identified in 4 cats at UC Davis Veterinary Medical Teaching Hospital between 1982 and 2011. Three had ulcerated, dark red mycetomas involving the dermis, subcutis, and fascia with fistulous tracts and/or regional lymphadenopathy. One cat had pyogranulomatous mesenteric lymphadenitis. Granulomatous inflammation in all cats contained colonies of Gram-positive, non-acid-fast organisms. All 4 cats failed to respond to aggressive medical and surgical treatment and were euthanized. Laser capture microdissection (LCM) was used to selectively harvest DNA from the affected formalin-fixed, paraffin-embedded (FFPE) tissues. Cloned amplicons from LCM-derived tissue confirmed the presence of Streptomyces spp in the dermatitis cases. Amplicons from the remaining cat with peritoneal involvement aligned with the 16S ribosomal RNA gene for Actinomycetales. Usually considered a contaminant, Streptomyces spp can be associated with refractory pyogranulomatous dermatitis and cellulitis in cats with outdoor access. LCM is useful in the diagnosis of bacterial diseases where contamination may be an issue.
C1 [Traslavina, R. P.; Reilly, C. M.; Samitz, E. M.; Stepnik, C. T.; Outerbridge, C.; Affolter, V. K.; Byrne, B. A.; Lowenstine, L. J.; White, S. D.; Murphy, B.] Univ Calif Davis, Sch Vet Med, Davis, CA 95616 USA.
[Traslavina, R. P.] NINDS, NIH, Sect Infect Nervous Syst, Bethesda, MD 20892 USA.
[Vasireddy, R.] Univ Texas Tyler, Hlth Sci Ctr, Tyler, TX 75799 USA.
RP Traslavina, RP (reprint author), NIH, 10 Ctr Dr,Bldg 10,Room 7C120, Bethesda, MD 20892 USA.
EM ryan.traslavina@nih.gov
NR 9
TC 1
Z9 1
U1 0
U2 0
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0300-9858
EI 1544-2217
J9 VET PATHOL
JI Vet. Pathol.
PD NOV
PY 2015
VL 52
IS 6
BP 1172
EP 1175
DI 10.1177/0300985814561094
PG 4
WC Pathology; Veterinary Sciences
SC Pathology; Veterinary Sciences
GA CW1FF
UT WOS:000364734300025
PM 25516065
ER
PT J
AU Zablotska, LB
Nadyrov, EA
Polyanskaya, ON
McConnell, RJ
O'Kane, P
Lubin, J
Hatch, M
Little, MP
Brenner, AV
Veyalkin, IV
Yauseyenka, VV
Bouville, A
Drozdovitch, VV
Minenko, VF
Demidchik, YE
Mabuchi, K
Rozhko, AV
AF Zablotska, Lydia B.
Nadyrov, Eldar A.
Polyanskaya, Olga N.
McConnell, Robert J.
O'Kane, Patrick
Lubin, Jay
Hatch, Maureen
Little, Mark P.
Brenner, Alina V.
Veyalkin, Ilya V.
Yauseyenka, Vasilina V.
Bouville, Andre
Drozdovitch, Vladimir V.
Minenko, Viktor F.
Demidchik, Yuri E.
Mabuchi, Kiyohiko
Rozhko, Alexander V.
TI Risk of Thyroid Follicular Adenoma Among Children and Adolescents in
Belarus Exposed to Iodine-131 After the Chornobyl Accident
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE adenoma; Chornobyl nuclear accident; dose-response relationship;
interaction; iodine deficiency; iodine radioisotopes; radiation; thyroid
neoplasms
ID DOSE-RESPONSE RELATIONSHIPS; POOLED ANALYSIS; CANCER; RADIATION;
CHILDHOOD; DISEASES; NODULES; COHORT; GUIDELINES; NEOPLASIA
AB Several studies reported an increased risk of thyroid cancer in children and adolescents exposed to radioactive iodines, chiefly iodine-131 (I-131), after the 1986 Chornobyl (Ukrainian spelling) nuclear power plant accident. The risk of benign thyroid tumors following such radiation exposure is much less well known. We have previously reported a novel finding of significantly increased risk of thyroid follicular adenoma in a screening study of children and adolescents exposed to the Chornobyl fallout in Ukraine. To verify this finding, we analyzed baseline screening data from a cohort of 11,613 individuals aged <= 18 years at the time of the accident in Belarus (mean age at screening = 21 years). All participants had individual I-131 doses estimated from thyroid radioactivity measurements and were screened according to a standardized protocol. We found a significant linear dose response for 38 pathologically confirmed follicular adenoma cases. The excess odds ratio per gray of 2.22 (95% confidence interval: 0.41, 13.1) was similar in males and females but decreased significantly with increasing age at exposure (P < 0.01), with the highest radiation risks estimated for those exposed at < 2 years of age. Follicular adenoma radiation risks were not significantly modified by most indicators of past and current iodine deficiency. The present study confirms the I-131-associated increases in risk of follicular adenoma in the Ukrainian population and adds new evidence on the risk increasing with decreasing age at exposure.
C1 [Zablotska, Lydia B.] Univ Calif San Francisco, Sch Med, Dept Epidemiol & Biostat, San Francisco, CA 94118 USA.
[Nadyrov, Eldar A.; Polyanskaya, Olga N.; Veyalkin, Ilya V.; Yauseyenka, Vasilina V.; Rozhko, Alexander V.] Republican Res Ctr Radiat Med & Human Ecol, Gomel, Byelarus.
[McConnell, Robert J.] Columbia Univ, Thyroid Ctr, New York, NY USA.
[O'Kane, Patrick] Thomas Jefferson Univ Hosp, Dept Radiol, Philadelphia, PA 19107 USA.
[Lubin, Jay; Hatch, Maureen; Little, Mark P.; Brenner, Alina V.; Bouville, Andre; Drozdovitch, Vladimir V.; Mabuchi, Kiyohiko] NCI, Radiat Oncol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Minenko, Viktor F.] Res Inst Nucl Problems, Minsk, Byelarus.
[Demidchik, Yuri E.] NN Alexandrov Natl Canc Ctr, Minsk, Byelarus.
RP Zablotska, LB (reprint author), Univ Calif San Francisco, Sch Med, Dept Epidemiol & Biostat, 3333 Calif St,Suite 280, San Francisco, CA 94118 USA.
EM Lydia.Zablotska@ucsf.edu
OI Little, Mark/0000-0003-0980-7567
FU National Cancer Institute [CA132918]; Intramural Research Program of the
Division of Cancer Epidemiology and Genetics; US Department of Energy;
Nuclear Regulatory Commission; [NO1-CP-21178]
FX Funding for this study was provided by the National Cancer Institute
(grant CA132918 to L.B.Z.; contract NO1-CP-21178 with L.B.Z., R.J.M.,
and P.O.; and funds from the Intramural Research Program of the Division
of Cancer Epidemiology and Genetics to J.L., M.H., M.P.L., A.V.B., A.B.,
V.V.D., and K.M.). The US Department of Energy provided funding at the
earlier stages of the study, and the Nuclear Regulatory Commission
provided the initial funds for purchase of equipment.
NR 38
TC 4
Z9 4
U1 0
U2 3
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0002-9262
EI 1476-6256
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD NOV 1
PY 2015
VL 182
IS 9
BP 781
EP 790
DI 10.1093/aje/kwv127
PG 10
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA CV0IX
UT WOS:000363935500010
PM 26443421
ER
PT J
AU Schinzari, F
Iantorno, M
Campia, U
Mores, N
Rovella, V
Tesauro, M
Di Daniele, N
Cardillo, C
AF Schinzari, Francesca
Iantorno, Micaela
Campia, Umberto
Mores, Nadia
Rovella, Valentina
Tesauro, Manfredi
Di Daniele, Nicola
Cardillo, Carmine
TI Vasodilator responses and endothelin-dependent vasoconstriction in
metabolically healthy obesity and the metabolic syndrome
SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
LA English
DT Article
DE obesity; endothelium; endothelin-1; metabolic syndrome; vasodilation
ID CARDIOVASCULAR-DISEASE; INSULIN-RESISTANCE; DIABETES-MELLITUS; SYSTEM
ACTIVITY; RISK; DYSFUNCTION; HYPERINSULINEMIA; ATHEROSCLEROSIS;
METAANALYSIS; OVERWEIGHT
AB Patients with metabolically healthy obesity (MHO) do not present the cluster of metabolic abnormalities that define the metabolic syndrome (MetS). Whether MHO is associated with lower impairment of vasoreactivity than the MetS is unknown. For this purpose, forearm blood flow (FBF) responses were measured by strain-gauge plethysmography during the intra-arterial infusion of acetylcholine (ACh), sodium nitroprusside (SNP), and/or the selective endothelin type A (ETA) receptor blocker BQ-123 in 119 obese individuals with MHO (n = 34) or with the MetS (n = 85) and in healthy lean controls (n = 56). ACh and SNP caused a significant vasodilation in both obese and lean participants (all P < 0.001). However, the response to both agents was significantly lower in the obese than in the control group (both P < 0.001). Among the obese participants, the reactivity to ACh was higher in MHO than in MetS patients, whereas the responsiveness to SNP was equally impaired in both groups (P = 0.45). Infusion of BQ-123 significantly increased FBF in obese patients (P < 0001), but not in the lean participants; hence, FBF following ETA receptor blockade was higher in both obese groups than in controls (both P < 0.001). FBF response to BQ-123 was significantly higher in patients with the MetS than in those with MHO (P = 0.007). In conclusion, patients with MHO have abnormal vascular reactivity, although their endothelial dysfunction is less pronounced than in patients with the MetS. These findings indicate that obesity is associated with vascular damage independent of those metabolic abnormalities underlying the MetS.
C1 [Schinzari, Francesca; Cardillo, Carmine] Univ Cattolica Sacro Cuore, Sch Med, Dept Internal Med, Rome, Italy.
[Iantorno, Micaela] NIH, Dept Crit Care Med, Bethesda, MD 20892 USA.
[Iantorno, Micaela] Johns Hopkins Univ Hosp, Dept Med, Baltimore, MD 21287 USA.
[Campia, Umberto] MedStar Cardiovasc Res Network, Washington, DC USA.
[Mores, Nadia] Univ Cattolica Sacro Cuore, Sch Med, Dept Pharmacol, Rome, Italy.
[Rovella, Valentina; Tesauro, Manfredi; Di Daniele, Nicola] Univ Roma Tor Vergata, Dept Internal Med, Rome, Italy.
RP Cardillo, C (reprint author), Univ Cattolica Sacro Cuore, Ist Patol Speciale Med & Semeiot Med, Largo Gemelli 8, I-00168 Rome, Italy.
EM carmine.cardillo@rm.unicatt.it
OI Cardillo, Carmine/0000-0001-5182-3005
FU Fondi d'Ateneo grants from Catholic University; Italian Ministry of
Health (Ministero della Salute) grant [RF-2010-2313809]
FX This work was partially supported by Fondi d'Ateneo grants from Catholic
University and from an Italian Ministry of Health (Ministero della
Salute) grant (RF-2010-2313809) to C. Cardillo.
NR 33
TC 7
Z9 7
U1 0
U2 3
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0193-1849
EI 1522-1555
J9 AM J PHYSIOL-ENDOC M
JI Am. J. Physiol.-Endocrinol. Metab.
PD NOV 1
PY 2015
VL 309
IS 9
BP E787
EP E792
DI 10.1152/ajpendo.00278.2015
PG 6
WC Endocrinology & Metabolism; Physiology
SC Endocrinology & Metabolism; Physiology
GA CV2CU
UT WOS:000364065300003
PM 26374766
ER
PT J
AU Varga, ZV
Ferdinandy, P
Liaudet, L
Pacher, P
AF Varga, Zoltan V.
Ferdinandy, Peter
Liaudet, Lucas
Pacher, Pal
TI Drug-induced mitochondrial dysfunction and cardiotoxicity
SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
LA English
DT Review
DE heart; heart failure; cardiomyopathy; toxicology; drug development;
reactive oxygen species
ID DOXORUBICIN-INDUCED CARDIOTOXICITY; INDUCED CARDIAC DYSFUNCTION;
MANGANESE SUPEROXIDE-DISMUTASE; MYOFIBRILLAR CREATINE-KINASE;
LEFT-VENTRICULAR DYSFUNCTION; PROTEIN-TYROSINE NITRATION; METASTATIC
BREAST-CANCER; HEART-FAILURE; OXIDATIVE STRESS; CELL-DEATH
AB Mitochondria has an essential role in myocardial tissue homeostasis; thus deterioration in mitochondrial function eventually leads to cardiomyocyte and endothelial cell death and consequent cardiovascular dysfunction. Several chemical compounds and drugs have been known to directly or indirectly modulate cardiac mitochondrial function, which can account both for the toxicological and pharmacological properties of these substances. In many cases, toxicity problems appear only in the presence of additional cardiovascular disease conditions or develop months/years following the exposure, making the diagnosis difficult. Cardiotoxic agents affecting mitochondria include several widely used anticancer drugs [anthracyclines (Doxorubicin/Adriamycin), cisplatin, trastuzumab (Herceptin), arsenic trioxide (Trisenox), mitoxantrone (Novantrone), imatinib (Gleevec), bevacizumab (Avastin), sunitinib (Sutent), and sorafenib (Nevaxar)], antiviral compound azidothymidine (AZT, Zidovudine) and several oral antidiabetics [e.g., rosiglitazone (Avandia)]. Illicit drugs such as alcohol, cocaine, methamphetamine, ecstasy, and synthetic cannabinoids (spice, K2) may also induce mitochondria-related cardiotoxicity. Mitochondrial toxicity develops due to various mechanisms involving interference with the mitochondrial respiratory chain (e.g., uncoupling) or inhibition of the important mitochondrial enzymes (oxidative phosphorylation, Szent-Gyorgyi-Krebs cycle, mitochondrial DNA replication, ADP/ATP translocator). The final phase of mitochondrial dysfunction induces loss of mitochondrial membrane potential and an increase in mitochondrial oxidative/nitrative stress, eventually culminating into cell death. This review aims to discuss the mechanisms of mitochondrion-mediated cardiotoxicity of commonly used drugs and some potential cardioprotective strategies to prevent these toxicities.
C1 [Varga, Zoltan V.; Pacher, Pal] NIAAA, Lab Cardiovasc Physiol & Tissue Injury, NIH, Bethesda, MD USA.
[Varga, Zoltan V.; Ferdinandy, Peter] Semmelweis Univ, Dept Pharmacol & Pharmacotherapy, Cardiometab Res Grp, H-1085 Budapest, Hungary.
[Ferdinandy, Peter] Pharmahungary Grp, Szeged, Hungary.
[Liaudet, Lucas] Univ Lausanne Hosp, Med Ctr, Dept Intens Care Med, Lausanne, Switzerland.
RP Pacher, P (reprint author), Lab Cardiovasc Physiol & Tissue Injury, 5625 Fishers Lane,Rm 2N-17, Bethesda, MD 20892 USA.
EM pacher@mail.nih.gov
RI Liaudet, Lucas/E-1322-2017
OI Liaudet, Lucas/0000-0003-2670-4930
FU Intramural Research Program of the of National Institutes of
Health/NIAAA; Rosztoczy Foundation
FX This study was supported by the Intramural Research Program of the of
National Institutes of Health/NIAAA (to P. Pacher). Z. V. Varga was
supported by the Rosztoczy Foundation.
NR 177
TC 24
Z9 26
U1 5
U2 42
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0363-6135
EI 1522-1539
J9 AM J PHYSIOL-HEART C
JI Am. J. Physiol.-Heart Circul. Physiol.
PD NOV 1
PY 2015
VL 309
IS 9
BP H1453
EP H1467
DI 10.1152/ajpheart.00554.2015
PG 15
WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular
Disease
SC Cardiovascular System & Cardiology; Physiology
GA CV2NH
UT WOS:000364092900007
PM 26386112
ER
PT J
AU Rauhauser, AA
Ren, CY
Lu, DM
Li, BH
Zhu, JL
McEnery, K
Vadnagara, K
Zepeda-Orozco, D
Zhou, XJ
Lin, FM
Jetten, AM
Attanasio, M
AF Rauhauser, Alysha A.
Ren, Chongyu
Lu, Dongmei
Li, Binghua
Zhu, Jili
McEnery, Kayla
Vadnagara, Komal
Zepeda-Orozco, Diana
Zhou, Xin J.
Lin, Fangming
Jetten, Anton M.
Attanasio, Massimo
TI Hedgehog signaling indirectly affects tubular cell survival after
obstructive kidney injury
SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
LA English
DT Article
DE hedgehog signaling; kidney injury; UUO
ID NG2 PROTEOGLYCAN; SONIC HEDGEHOG; GROWTH-FACTOR; FIBROSIS; MACROPHAGES;
ACTIVATION; REPAIR; PROLIFERATION; FIBROBLASTS; PERICYTES
AB Hedgehog (Hh) is an evolutionary conserved signaling pathway that has important functions in kidney morphogenesis and adult organ maintenance. Recent work has shown that Hh signaling is reactivated in the kidney after injury and is an important mediator of progressive fibrosis. Pericytes and fibroblasts have been proposed to be the principal cells that respond to Hh ligands, and pharmacological attenuation of Hh signaling has been considered as a possible treatment for fibrosis, but the effect of Hh inhibition on tubular epithelial cells after kidney injury has not been reported. Using genetically modified mice in which tubule-derived hedgehog signaling is increased and mice in which this pathway is conditionally suppressed in pericytes that express the proteoglycan neuron glial protein 2 (NG2), we found that suppression of Hh signaling is associated with decreased macrophage infiltration and tubular proliferation but also increased tubular apoptosis, an effect that correlated with the reduction of tubular beta-catenin activity. Collectively, our data suggest a complex function of hedgehog signaling after kidney injury in initiating both reparative and proproliferative, prosurvival processes.
C1 [Rauhauser, Alysha A.; Ren, Chongyu; Lu, Dongmei; Li, Binghua; Zhu, Jili; McEnery, Kayla; Vadnagara, Komal; Attanasio, Massimo] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Dallas, TX 75390 USA.
[Zhu, Jili] Wuhan Univ, Dept Nephrol, Wuhan 430072, Hubei, Peoples R China.
[Zepeda-Orozco, Diana] Univ Iowa, Dept Pediat, Iowa City, IA 52242 USA.
[Zhou, Xin J.] Baylor Univ, Med Ctr, Pathologist BioMed Labs, Renal Path Diagnost, Dallas, TX USA.
[Zhou, Xin J.] Baylor Univ, Med Ctr, Dept Pathol, Dallas, TX USA.
[Lin, Fangming] Columbia Univ, Dept Pediat Pathol & Cell Biol, New York, NY USA.
[Jetten, Anton M.] NIEHS, Cell Biol Sect, Div Intramural Res, NIH, Res Triangle Pk, NC 27709 USA.
[Attanasio, Massimo] Univ Texas SW Med Ctr Dallas, Eugene McDermott Ctr Growth & Dev, Dallas, TX 75390 USA.
RP Attanasio, M (reprint author), Univ Texas SW Med Ctr Dallas, 5323 Harry Hines Blvd, Dallas, TX 75390 USA.
EM massimo.attanasio@utsouthwestern.edu
OI Jetten, Anton/0000-0003-0954-4445
FU National Institute of Diabetes and Digestive and Kidney Diseases
[1R01DK090326-01A1]; Satellite Healthcare Norman Coplon Extramural
Research Award; American Society of Nephrology Norman Siegel Research
Scholar Grant
FX This work was supported by the National Institute of Diabetes and
Digestive and Kidney Diseases Grant 1R01DK090326-01A1, a Satellite
Healthcare Norman Coplon Extramural Research Award, and an American
Society of Nephrology Norman Siegel Research Scholar Grant.
NR 27
TC 4
Z9 4
U1 1
U2 1
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 1931-857X
EI 1522-1466
J9 AM J PHYSIOL-RENAL
JI Am. J. Physiol.-Renal Physiol.
PD NOV 1
PY 2015
VL 309
IS 9
BP F770
EP F778
DI 10.1152/ajprenal.00232.2015
PG 9
WC Physiology; Urology & Nephrology
SC Physiology; Urology & Nephrology
GA CV2QO
UT WOS:000364101600003
PM 26290370
ER
PT J
AU Stein, MB
Kessler, RC
Heeringa, SG
Jain, S
Campbell-Sills, L
Colpe, LJ
Fullerton, CS
Nock, MK
Sampson, NA
Schoenbaum, M
Sun, XY
Thomas, ML
Ursano, RJ
AF Stein, Murray B.
Kessler, Ronald C.
Heeringa, Steven G.
Jain, Sonia
Campbell-Sills, Laura
Colpe, Lisa J.
Fullerton, Carol S.
Nock, Matthew K.
Sampson, Nancy A.
Schoenbaum, Michael
Sun, Xiaoying
Thomas, Michael L.
Ursano, Robert J.
CA Army STARRS Collaborators
TI Prospective Longitudinal Evaluation of the Effect of Deployment-Acquired
Traumatic Brain Injury on Posttraumatic Stress and Related Disorders:
Results From the Army Study to Assess Risk and Resilience in
Servicemembers (Army STARRS)
SO AMERICAN JOURNAL OF PSYCHIATRY
LA English
DT Article
ID MILITARY PERSONNEL; CLINICAL PRESENTATION; MENTAL-HEALTH; SUICIDE RISK;
SYMPTOMS; PTSD; DEPRESSION; ASSOCIATION; IRAQ; TBI
AB Objective: Traumatic brain injury (TBI) is increasingly recognized as a risk factor for deleterious mental health and functional outcomes. The purpose of this study was to examine the strength and specificity of the association between deployment-acquired TBI and subsequent posttraumatic stress and related disorders among U.S. Army personnel.
Method: A prospective, longitudinal survey of soldiers in three Brigade CombatTeams was conducted 1-2 months prior to an average 10-month deployment to Afghanistan (T0), upon redeployment to the United States (T1), approximately 3 months later (T2), and approximately 9 months later (T3). Outcomes of interest were 30-day prevalence. postdeployment of posttraumatic stress disorder (PTSD), major depressive episode, generalized anxiety disorder, and suicidality, as well as presence and severity of postdeployment PTSD symptoms.
Results: Complete information was available for 4,645 soldiers. Approximately one in five soldiers reported exposure to mild (18.0%) or more-than-mild (1.2%) TBI(s) during the index deployment. Even after adjusting for other risk factors (e g., predeployment mental health status, severity of deployment stress, prior TBI history), deployment-acquired TBI was associated with elevated adjusted odds of PTSD and generalized anxiety disorder at T2 and T3 and of major depressive episode at T2. Suicidality risk at T2 appeared similarly elevated, but this association did not reach statistical significance.
Conclusions: The findings highlight the importance of surveillance efforts to identify soldiers who have sustained TBIs and are therefore at risk for an array of postdeployment adverse mental health outcomes, including but not limited to PTSD. The mechanism(s) accounting for these associations need to be elucidated to inform development of effective preventive and early intervention programs.
C1 [Stein, Murray B.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA.
Univ Calif San Diego, Dept Family Med & Publ Hlth, La Jolla, CA 92093 USA.
VA San Diego Healthcare Syst, San Diego, CA USA.
Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA.
Univ Michigan, Inst Social Res, Ann Arbor, MI USA.
NIMH, Bethesda, MD 20892 USA.
Uniformed Serv Univ Hlth Sci, Dept Psychiat, Ctr Study Traumat Stress, Bethesda, MD 20814 USA.
Harvard Univ, Dept Psychol, Cambridge, MA USA.
RP Stein, MB (reprint author), Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA.
EM mstein@ucsd.edu
FU Department of the Army [U01MH087981]; U S. Department of Health and
Human Services, National Institutes of Health, National Institute of
Mental Health (NIH/NIMH)
FX Army STARRS was sponsored by the Department of the Army and funded under
cooperative agreement number U01MH087981 with the U S. Department of
Health and Human Services, National Institutes of Health, National
Institute of Mental Health (NIH/NIMH).
NR 40
TC 10
Z9 10
U1 4
U2 10
PU AMER PSYCHIATRIC PUBLISHING, INC
PI ARLINGTON
PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA
SN 0002-953X
EI 1535-7228
J9 AM J PSYCHIAT
JI Am. J. Psychiat.
PD NOV
PY 2015
VL 172
IS 11
BP 1101
EP 1111
DI 10.1176/appi.ajp.2015.14121572
PG 11
WC Psychiatry
SC Psychiatry
GA CV0CJ
UT WOS:000363914700013
PM 26337036
ER
PT J
AU Kunii, Y
Zhang, WY
Xu, Q
Hyde, TM
McFadden, W
Shin, JH
Deep-Soboslay, A
Ye, TZ
Li, C
Kleinman, JE
Wang, KH
Lipska, BK
AF Kunii, Yasuto
Zhang, Wenyu
Xu, Qing
Hyde, Thomas M.
McFadden, Whitney
Shin, Joo Heon
Deep-Soboslay, Amy
Ye, Tianzhang
Li, Chao
Kleinman, Joel E.
Wang, Kuan Hong
Lipska, Barbara K.
TI CHRNA7 and CHRFAM7A mRNAs: Co-Localized and Their Expression Levels
Altered in the Postmortem Dorsolateral Prefrontal Cortex in Major
Psychiatric Disorders
SO AMERICAN JOURNAL OF PSYCHIATRY
LA English
DT Article
ID RECEPTOR SUBUNIT GENE; NICOTINIC ACETYLCHOLINE-RECEPTORS; BIPOLAR
DISORDER; BINDING-SITES; DEPRESSIVE DISORDER; PARTIAL DUPLICATION;
ALPHA-BUNGAROTOXIN; FRONTAL-CORTEX; MOUSE-BRAIN; RAT-BRAIN
AB Objective: CHRNA7, coding alpha-7 nicotinic acetylcholine receptor (alpha 7 nAChR), is involved in cognition through interneuron modulation of dopamine and glutamate signaling. CHRNA7 and its partially duplicated chimeric gene CHRFAM7A have been implicated in schizophrenia through linkage and association studies.
Method: Expression of CHRNA7 and CHRFAM7A mRNA was measured in the postmortem prefrontal cortex in more than 700 subjects, including patients with schizophrenia, bipolar disorder, major depression, and normal comparison subjects. The effects of antipsychotics and nicotine, as well as associations of CHRNA7 SNPs with gene expression, were explored. Fluorescent in-situ hybridization was used to examine coexpression of both transcripts in the human cortex.
Results: CHRFAM7A expression and CHRFAM7A/CHRNA7 ratios were higher in fetal compared with postnatal life, whereas CHRNA7 expression was relatively stable. CHRFAM7A expression was significantly elevated in all diagnostic groups, while CHRNA7 expression was reduced in the schizophrenia group and increased in the major depression group compared with the comparison group. CHRFAM7A/CHRNA7 ratios were significantly increased in the schizophrenia and bipolar disorder groups compared with the comparison group There was no effect of nicotine or antipsychotics and no association of SNPs in CHRNA7 with expression. CHRNA7 and CHRFAM7A mRNAs were expressed in the same neuronal nuclei of the human neocortex.
Conclusions: These data show preferential fetal CHRFAM7A expression in the human prefrontal cortex and suggest abnormalities in the CHRFAM7A/CHRNA7 ratios in schizophrenia and bipolar disorder, due mainly to overexpression of CHRFAM7A. Given that these transcripts are coexpressed in a subset of human cortical neurons and can interact to alter function of nAChRs, these results support the concept of aberrant function of nAChRs in mental illness.
C1 [Lipska, Barbara K.] NIMH, Human Brain Collect Core, Div Intramural Res Programs, NIH, Bethesda, MD 20892 USA.
Fukushima Med Univ, Sch Med, Dept Neuropsychiat, Fukushima, Fukushima, Japan.
NIMH, Unit Neural Circuits & Adapt Behav, NIH, Bethesda, MD 20892 USA.
Lieber Inst Brain Dev, Baltimore, MD USA.
Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD USA.
Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA.
RP Lipska, BK (reprint author), NIMH, Human Brain Collect Core, Div Intramural Res Programs, NIH, Bethesda, MD 20892 USA.
EM lipskab@mail.nih.gov
RI Wang, Kuan Hong/J-1150-2016; Lipska, Barbara/E-4569-2017
OI Wang, Kuan Hong/0000-0002-2249-5417;
FU Intramural Research Program of the National Institute of Mental Health
at the National Institutes of Health
FX Supported by the Intramural Research Program of the National Institute
of Mental Health at the National Institutes of Health.
NR 45
TC 3
Z9 3
U1 1
U2 6
PU AMER PSYCHIATRIC PUBLISHING, INC
PI ARLINGTON
PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA
SN 0002-953X
EI 1535-7228
J9 AM J PSYCHIAT
JI Am. J. Psychiat.
PD NOV
PY 2015
VL 172
IS 11
BP 1122
EP 1130
DI 10.1176/appi.ajp.2015.14080978
PG 9
WC Psychiatry
SC Psychiatry
GA CV0CJ
UT WOS:000363914700015
PM 26206074
ER
PT J
AU Schaffer, A
Isometsa, ET
Azorin, JM
Cassidy, F
Goldstein, T
Rihmer, Z
Sinyor, M
Tondo, L
Moreno, DH
Turecki, G
Reis, C
Kessing, LV
Ha, K
Weizman, A
Beautrais, A
Chou, YH
Diazgranados, N
Levitt, AJ
Zarate, CA
Yatham, L
AF Schaffer, Ayal
Isometsa, Erkki T.
Azorin, Jean-Michel
Cassidy, Frederick
Goldstein, Tina
Rihmer, Zoltan
Sinyor, Mark
Tondo, Leonardo
Moreno, Doris H.
Turecki, Gustavo
Reis, Catherine
Kessing, Lars Vedel
Ha, Kyooseob
Weizman, Abraham
Beautrais, Annette
Chou, Yuan-Hwa
Diazgranados, Nancy
Levitt, Anthony J.
Zarate, Carlos A., Jr.
Yatham, Lakshmi
TI A review of factors associated with greater likelihood of suicide
attempts and suicide deaths in bipolar disorder: Part II of a report of
the International Society for Bipolar Disorders Task Force on Suicide in
Bipolar Disorder
SO AUSTRALIAN AND NEW ZEALAND JOURNAL OF PSYCHIATRY
LA English
DT Review
DE Bipolar disorder; suicide; suicide attempts
ID MAJOR AFFECTIVE-DISORDER; NATIONAL EPIDEMIOLOGIC SURVEY; COMORBID
ANXIETY DISORDERS; SUBSTANCE USE DISORDERS; ALCOHOL-USE DISORDERS;
AGE-OF-ONSET; RISK-FACTORS; FAMILY-HISTORY; CLINICAL CHARACTERISTICS;
PREDOMINANT POLARITY
AB Objectives: Many factors influence the likelihood of suicide attempts or deaths in persons with bipolar disorder. One key aim of the International Society for Bipolar Disorders Task Force on Suicide was to summarize the available literature on the presence and magnitude of effect of these factors.
Methods: A systematic review of studies published from 1 January 1980 to 30 May 2014 identified using keywords bipolar disorder' and suicide attempts or suicide'. This specific paper examined all reports on factors putatively associated with suicide attempts or suicide deaths in bipolar disorder samples. Factors were subcategorized into: (1) sociodemographics, (2) clinical characteristics of bipolar disorder, (3) comorbidities, and (4) other clinical variables.
Results: We identified 141 studies that examined how 20 specific factors influenced the likelihood of suicide attempts or deaths. While the level of evidence and degree of confluence varied across factors, there was at least one study that found an effect for each of the following factors: sex, age, race, marital status, religious affiliation, age of illness onset, duration of illness, bipolar disorder subtype, polarity of first episode, polarity of current/recent episode, predominant polarity, mood episode characteristics, psychosis, psychiatric comorbidity, personality characteristics, sexual dysfunction, first-degree family history of suicide or mood disorders, past suicide attempts, early life trauma, and psychosocial precipitants.
Conclusion: There is a wealth of data on factors that influence the likelihood of suicide attempts and suicide deaths in people with bipolar disorder. Given the heterogeneity of study samples and designs, further research is needed to replicate and determine the magnitude of effect of most of these factors. This approach can ultimately lead to enhanced risk stratification for patients with bipolar disorder.
C1 [Schaffer, Ayal] ISBD, Task Force Suicide, Pittsburgh, PA USA.
[Schaffer, Ayal; Reis, Catherine] Sunnybrook Hlth Sci Ctr, Dept Psychiat, Mood & Anxiety Disorders Program, Toronto, ON M4N 3M5, Canada.
[Schaffer, Ayal; Sinyor, Mark; Levitt, Anthony J.] Univ Toronto, Dept Psychiat, Toronto, ON, Canada.
[Isometsa, Erkki T.] Univ Helsinki, Inst Clin Med, Dept Psychiat, Helsinki, Finland.
[Azorin, Jean-Michel] St Marguerite Hosp, Dept Adult Psychiat, Marseille, France.
[Azorin, Jean-Michel] Univ Aix Marseille 2, F-13284 Marseille 07, France.
[Cassidy, Frederick] Duke Univ, Dept Psychiat & Behav Sci, Div Brain Stimulat & Neurophysiol, Durham, NC USA.
[Goldstein, Tina] Univ Pittsburgh, Sch Med, Western Psychiat Inst & Clin, Dept Child & Adolescent Psychiat, Pittsburgh, PA USA.
[Rihmer, Zoltan] Semmelweis Univ, Dept Clin & Theoret Mental Hlth, Budapest, Hungary.
[Rihmer, Zoltan] Semmelweis Univ, Dept Psychiat & Psychotherapy, Budapest, Hungary.
[Sinyor, Mark; Levitt, Anthony J.] Sunnybrook Hlth Sci Ctr, Dept Psychiat, Toronto, ON M4N 3M5, Canada.
[Tondo, Leonardo] Lucio Bini Ctr, Cagliari, Italy.
[Tondo, Leonardo] Harvard Univ, Sch Med, Boston, MA USA.
[Tondo, Leonardo] McLean Hosp, Belmont, MA 02178 USA.
[Moreno, Doris H.] Univ Sao Paulo, Dept & Inst Psychiat, Sect Psychiat Epidemiol, Sao Paulo, Brazil.
[Moreno, Doris H.] Univ Sao Paulo, Dept & Inst Psychiat, Mood Disorders Unit, Sao Paulo, Brazil.
[Turecki, Gustavo] McGill Univ, Dept Psychiat, Res & Acad Affairs, Montreal, PQ, Canada.
[Turecki, Gustavo] McGill Grp Suicide Studies, Montreal, PQ, Canada.
[Turecki, Gustavo] Douglas Inst, Depress Disorders Program, Montreal, PQ, Canada.
[Turecki, Gustavo] McGill Univ, Dept Psychiat, Dept Human Genet, Montreal, PQ, Canada.
[Turecki, Gustavo] McGill Univ, Dept Neurol & Neurosurg, Montreal, PQ, Canada.
[Kessing, Lars Vedel] Univ Copenhagen, Fac Hlth Sci, Psychiat Ctr Copenhagen, Copenhagen, Denmark.
[Ha, Kyooseob] Seoul Natl Univ, Bundang Hosp, Mood Disorders Clin & Affect Neurosci Lab, Songnam, South Korea.
[Ha, Kyooseob] Korea Assoc Suicide Prevent, Seoul, South Korea.
[Weizman, Abraham] Felsenstein Med Res Ctr, Lab Biol Psychiat, Petah Tiqwa, Israel.
[Weizman, Abraham] Geha Mental Hlth Ctr, Res Unit, Petah Tiqwa, Israel.
[Weizman, Abraham] Tel Aviv Univ, Sackler Fac Med, Dept Psychiat, IL-69978 Tel Aviv, Israel.
[Beautrais, Annette] Yale Univ, Yale Sch Med, Dept Emergency Med, New Haven, CT USA.
[Chou, Yuan-Hwa] Natl Yang Ming Univ, Taipei Vet Gen Hosp, Dept Psychiat, Sect Psychosomat Med, Taipei 112, Taiwan.
[Diazgranados, Nancy] NIAAA, Lab Clin & Translat Studies, Bethesda, MD USA.
[Zarate, Carlos A., Jr.] NIMH, Expt Therapeut & Pathophysiol Branch, Div Intramural Res Programs, Bethesda, MD 20892 USA.
[Yatham, Lakshmi] Univ British Columbia, Dept Psychiat, Vancouver, BC V5Z 1M9, Canada.
RP Schaffer, A (reprint author), Sunnybrook Hlth Sci Ctr, Dept Psychiat, Mood & Anxiety Disorders Program, 2075 Bayview Ave,Room FG 52, Toronto, ON M4N 3M5, Canada.
EM ayal.schaffer@sunnybrook.ca
FU Brenda Smith Bipolar Disorder Research Fund, Sunnybrook Health Sciences
Centre, University of Toronto
FX Partial support for this project was provided by the Brenda Smith
Bipolar Disorder Research Fund, Sunnybrook Health Sciences Centre,
University of Toronto.
NR 156
TC 6
Z9 6
U1 7
U2 21
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 0004-8674
EI 1440-1614
J9 AUST NZ J PSYCHIAT
JI Aust. N. Z. J. Psych.
PD NOV
PY 2015
VL 49
IS 11
SI SI
BP 1006
EP 1020
DI 10.1177/0004867415594428
PG 15
WC Psychiatry
SC Psychiatry
GA CV0UV
UT WOS:000363970000010
PM 26175498
ER
PT J
AU Pfefferkorn, CM
Walker, RL
He, Y
Gruschus, JM
Lee, JC
AF Pfefferkorn, Candace M.
Walker, Robert L., III
He, Yi
Gruschus, James M.
Lee, Jennifer C.
TI Tryptophan probes reveal residue-specific phospholipid interactions of
apolipoprotein C-III
SO BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
LA English
DT Article
DE Fluorescence; Circular dichroism; Penetration depth; Protein-lipid
interaction
ID LIPOPROTEIN-LIPASE ACTIVITY; LIPID-PROTEIN INTERACTIONS; CARDIOVASCULAR
RISK-FACTOR; MEMBRANE-PROTEIN; PLASMA-LIPOPROTEINS; AMPHIPATHIC HELIX;
PARTICLE-SIZE; FLUORESCENCE; DEPTH; DISPLACEMENT
AB Apolipoproteins are essential human proteins for lipid metabolism. Together with phospholipids, they constitute lipoproteins, nm to pm sized particles responsible for transporting cholesterol and triglycerides throughout the body. To investigate specific protein-lipid interactions, we produced and characterized three single-Trp containing apolipoprotein (ApoCIII) variants (W42 (W54F/W65F), W54 (W42F/W65F), W65 (W42F/W54F)). Upon binding to phospholipid vesicles, wild-type ApoCIII adopts an a-helical conformation (50% helicity) as determined by circular dichroism spectroscopy with an approximate apparent partition constant of 3 x 10(4) M-1 Steady-state and time-resolved fluorescence measurements reveal distinct residue-specific behaviors with W54 experiencing the most hydrophobic environment followed by W42 and W65. Interestingly, time-resolved anisotropy measurements show a converse trend for relative Trp mobility with position 54 being the least immobile. To determine the relative insertion depths of W42, W54, and W65 in the bilayer, fluorescence quenching experiments were performed using three different brominated lipids. W65 had a clear preference for residing near the headgroup while W54 and W42 sample the range of depths similar to 8-11 angstrom from the bilayer center. On average, W54 is slightly more embedded than W42. Based on Trp spectral differences between ApoCIII binding to phospholipid vesicles and sodium dodecyl sulfate micelles, we suggest that ApoCIII adopts an alternate helical conformation on the bilayer which could have functional implications. Published by Elsevier B.V.
C1 [Pfefferkorn, Candace M.; Walker, Robert L., III; Gruschus, James M.; Lee, Jennifer C.] NHLBI, Lab Mol Biophys, NIH, Bethesda, MD 20892 USA.
[He, Yi] NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA.
RP Lee, JC (reprint author), NHLBI, Lab Mol Biophys, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM leej4@mail.nih.gov
RI Lee, Jennifer/E-9658-2015
OI Lee, Jennifer/0000-0003-0506-8349
FU Intramural Research Program at the National Institutes of Health,
National Heart, Lung, and Blood Institute (NHLBI)
FX This work is supported by the Intramural Research Program at the
National Institutes of Health, National Heart, Lung, and Blood Institute
(NHLBI). DLS and CD measurements were performed using instruments in the
NHLBI Biophysics Core Facility. We thank Duck-Yeon Lee (Biochemistry
Core Facility, NHLBI) for the technical assistance with mass
spectrometry.
NR 47
TC 1
Z9 1
U1 2
U2 6
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0005-2736
EI 0006-3002
J9 BBA-BIOMEMBRANES
JI Biochim. Biophys. Acta-Biomembr.
PD NOV
PY 2015
VL 1848
IS 11
BP 2821
EP 2828
DI 10.1016/j.bbamem.2015.08.018
PN A
PG 8
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA CV4XW
UT WOS:000364270800007
PM 26301570
ER
PT J
AU Joo, HS
Otto, M
AF Joo, Hwang-Soo
Otto, Michael
TI Mechanisms of resistance to antimicrobial peptides in staphylococci
SO BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
LA English
DT Review
DE Staphylococcus aureus; Staphylococcus epidermidis; Antimicrobial
peptides; Bacterial resistance
ID WALL TEICHOIC-ACID; GRAM-POSITIVE BACTERIA; PHENOL-SOLUBLE MODULINS;
POLYSACCHARIDE INTERCELLULAR ADHESIN; VANCOMYCIN-INTERMEDIATE
RESISTANCE; 2-COMPONENT REGULATORY SYSTEM; ALANYL-LIPOTEICHOIC ACID;
VRAFG ABC TRANSPORTER; PSEUDOMONAS-AERUGINOSA; BIOFILM FORMATION
AB Staphylococci are commensal bacteria living on the epithelial surfaces of humans and other mammals. Many staphylococci, including the dangerous pathogen Staphylococcus aureus, can cause severe disease when they breach the epithelial barrier. Both during their commensal life and during infection, staphylococci need to evade mechanisms of innate host defense, of which antimicrobial peptides (AMPs) play a key role in particular on the skin. Mechanisms that staphylococci have developed to evade the bactericidal activity of AMPs are manifold, comprising repulsion of AMPs via alteration of cell wall and membrane surface charges, proteolytic inactivation, sequestration, and secretion. Furthermore, many staphylococci form biofilms, which represents an additional way of protection from antimicrobial agents, including AMPs. Finally, staphylococci can sense the presence of AMPs by sensor/regulator systems that control many of those resistance mechanisms. This article is part of a Special Issue entitled: Bacterial Resistance to Antimicrobial Peptides. Published by Elsevier B.V.
C1 [Joo, Hwang-Soo; Otto, Michael] NIAID, Pathogen Mol Genet Sect, Lab Human Bacterial Pathogenesis, US Natl Inst Hlth,NIH, Bethesda, MD 20892 USA.
RP Otto, M (reprint author), 9000 Rockville Pike,Bldg 33 1W10A, Bethesda, MD 20892 USA.
EM motto@niaid.nih.gov
OI Otto, Michael/0000-0002-2222-4115; JOO, HWANG-SOO/0000-0003-4668-3225
FU Intramural Research Program of the National Institute of Allergy and
Infectious Diseases (NIAID), U.S. National Institutes of Health (NIH)
[ZIA AI000904-14]
FX This study was supported by the Intramural Research Program of the
National Institute of Allergy and Infectious Diseases (NIAID), U.S.
National Institutes of Health (NIH), grant ZIA AI000904-14.
NR 104
TC 10
Z9 10
U1 6
U2 36
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0005-2736
EI 0006-3002
J9 BBA-BIOMEMBRANES
JI Biochim. Biophys. Acta-Biomembr.
PD NOV
PY 2015
VL 1848
IS 11
SI SI
BP 3055
EP 3061
DI 10.1016/j.bbamem.2015.02.009
PN B
PG 7
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA CV4XX
UT WOS:000364270900006
PM 25701233
ER
PT J
AU Saunders, EFH
Reider, A
Singh, G
Gelenberg, AJ
Rapoport, SI
AF Saunders, Erika F. H.
Reider, Aubrey
Singh, Gagan
Gelenberg, Alan J.
Rapoport, Stanley I.
TI Low unesterified:esterified eicosapentaenoic acid (EPA) plasma
concentration ratio is associated with bipolar disorder episodes, and
omega-3 plasma concentrations are altered by treatment
SO BIPOLAR DISORDERS
LA English
DT Article
DE bipolar disorder; eicosapentaenoic acid; inflammation; omega-3
ID POLYUNSATURATED FATTY-ACIDS; PLACEBO-CONTROLLED TRIAL; TASK-FORCE
REPORT; OPEN-LABEL TRIAL; DOUBLE-BLIND; N-3 PUFA; DOCOSAHEXAENOIC ACID;
CLINICAL-TRIAL; INTERNATIONAL-SOCIETY; BRAIN PHOSPHOLIPIDS
AB ObjectivesOmega (n)-3 and n-6 polyunsaturated fatty acids (PUFAs) are molecular modulators of neurotransmission and inflammation. We hypothesized that plasma concentrations of n-3 PUFAs would be lower and those of n-6 PUFAs higher in subjects with bipolar disorder (BD) compared to healthy controls (HCs), and would correlate with symptom severity in subjects with BD, and that effective treatment would correlate with increased n-3 but lower n-6 PUFA levels. Additionally, we explored clinical correlations and group differences in plasma levels of saturated and monounsaturated fatty acids.
MethodsThis observational, parallel group study compared biomarkers between HCs (n=31) and symptomatic subjects with BD (n=27) when ill and after symptomatic recovery (follow-up). Plasma concentrations of five PUFAs [linoleic acid (LA), arachidonic acid (AA), alpha-linolenic acid (ALA), docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA)], two saturated fatty acids (palmitic acid and stearic acid) and two monounsaturated fatty acids (palmitoleic acid and oleic acid) were measured in esterified (E) and unesterified (UE) forms. Calculated ratios included UE:E for the five PUFAs, ratios of n-3 PUFAs (DHA:ALA, EPA:ALA and EPA:DHA), and the ratio of n-6:n-3 AA:EPA. Comparisons of plasma fatty acid levels and ratios between BD and HC groups were made with Student t-tests, and between the BD group at baseline and follow-up using paired t-tests. Comparison of categorical variables was performed using chi-square tests. Pearson's r was used for bivariate correlations with clinical variables, including depressive and manic symptoms, current panic attacks, and psychosis.
ResultsUE EPA was lower in subjects with BD than in HCs, with a large effect size (Cohen's d=0.86, p<0.002); however, it was not statistically significant after correction for multiple comparisons. No statistically significant difference was seen in any plasma PUFA concentration between the BD and HC groups after Bonferroni correction for 40 comparisons, at p<0.001. Neither depressive severity nor mania severity was correlated significantly with any PUFA concentration. Exploratory comparison showed lower UE:E EPA in the BD than the HC group (p<0.0001). At follow-up in the BD group, UE, E DHA:ALA, and UE EPA:ALA were decreased (p<0.002). Exploratory correlations of clinical variables revealed that mania severity and suicidality were positively correlated with UE:E EPA ratio, and that several plasma levels and ratios correlated with panic disorder and psychosis. Depressive severity was not correlated with any ratio. No plasma fatty acid level or ratio correlated with self-reported n-3 PUFA intake or use of medication by class.
ConclusionsA large effect size of reduced UE EPA, and a lower plasma UE:E concentration ratio of EPA in the symptomatic BD state may be important factors in vulnerability to a mood state. Altered n-3 PUFA ratios could indicate changes in PUFA metabolism concurrent with symptom improvement. Our findings are consistent with preclinical and postmortem data and suggest testing interventions that increase n-3 and decrease n-6 dietary PUFA intake.
C1 [Saunders, Erika F. H.; Reider, Aubrey; Singh, Gagan; Gelenberg, Alan J.] Penn State Coll Med, Penn State Milton S Hershey Med Ctr, Dept Psychiat, Hershey, PA 17033 USA.
[Saunders, Erika F. H.] Univ Michigan, Dept Psychiat, Ann Arbor, MI 48109 USA.
[Saunders, Erika F. H.] Univ Michigan, Depress Ctr, Ann Arbor, MI 48109 USA.
[Rapoport, Stanley I.] NIA, Brain Physiol & Metab Sect, Lab Neurosci, NIH, Bethesda, MD 20892 USA.
RP Saunders, EFH (reprint author), Penn State Coll Med, Penn State Milton S Hershey Med Ctr, Dept Psychiat, 500 Univ Dr,POB 850 Mail Code HO73, Hershey, PA 17033 USA.
EM esaunders@hmc.psu.edu
FU National Center for Research Resources [KL2 RR033180]; National Center
for Advancing Translational Sciences [KL2 TR000126]; Intramural Program
of the National Institute on Aging, NIH
FX The authors wish to acknowledge the participants in the study who
donated time and effort to research. The project described was supported
by the National Center for Research Resources, Grant KL2 RR033180
(EFHS), now the National Center for Advancing Translational Sciences,
Grant KL2 TR000126. We thank Mr. Kaizong Ma at the Brain Physiology and
Metabolism Section, Laboratory of Neurosciences, National Institute on
Aging, National Institutes of Health (NIH) for performing the plasma
fatty acid analyses. The contributions of Kaizong Ma and SIR were
supported entirely by the Intramural Program of the National Institute
on Aging, NIH. SIR has no conflict of interest with regard to this
paper. The content is solely the responsibility of the authors and does
not necessarily represent the official views of the NIH. The sponsors of
this research did not have direct influence over the collection,
analysis or interpretation of data.
NR 103
TC 6
Z9 6
U1 2
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1398-5647
EI 1399-5618
J9 BIPOLAR DISORD
JI Bipolar Disord.
PD NOV
PY 2015
VL 17
IS 7
BP 729
EP 742
DI 10.1111/bdi.12337
PG 14
WC Clinical Neurology; Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA CU9UD
UT WOS:000363890100004
PM 26424416
ER
PT J
AU Morken, NH
Skjaerven, R
Wilcox, AJ
AF Morken, N-H
Skjaerven, R.
Wilcox, A. J.
TI Ultrasound prediction of perinatal outcome: the unrecognised value of
sibling data
SO BJOG-AN INTERNATIONAL JOURNAL OF OBSTETRICS AND GYNAECOLOGY
LA English
DT Article
DE Fetal size; perinatal mortality; prediction; small for gestational age;
ultrasound
ID LAST MENSTRUAL PERIOD; LOW-BIRTH-WEIGHT; GESTATIONAL-AGE; BIPARIETAL
DIAMETER; EARLY-PREGNANCY; INCREASED RISK; NORWAY; DELIVERY; BIOMETRY;
GROWTH
AB ObjectiveTo identify high-risk fetuses at the first routinely performed ultrasound examination by making use of information from the mother's previous pregnancy.
DesignA population-based cohort study.
SettingNorway, 1999-2009.
PopulationAll singleton first live births and their second-born siblings registered in the Medical Birth Registry of Norway (166786 eligible sibling pairs).
MethodsOdds ratios were calculated by logistic regression.
Main outcome measuresVery small for gestational age (vSGA; birthweight -1.96 standard deviations) and perinatal death (stillbirth at 22weeks of gestation or death within 28days of life).
ResultsSmall fetal size at ultrasound (i.e. a fetus smaller than expected by last menstrual period, LMP) is only weakly predictive of vSGA or perinatal death; however, if the firstborn sibling was vSGA at birth, ultrasound measures in the next pregnancy become strongly informative of risk. The smaller the fetal size on ultrasound, the higher its risk of vSGA (3-18%; P-trend<0.0001) and perinatal death (4-19 per thousand, P-trend=0.012). In contrast, if the first baby was not vSGA, small fetal size on ultrasound is uninformative.
ConclusionsWhen the firstborn baby is vSGA, discrepancies between fetal size on ultrasound and LMP become highly predictive of risk of vSGA and perinatal mortality in the second-born infant. The value of combining these routinelycollected clinical data has not previously been recognised.
C1 [Morken, N-H; Skjaerven, R.] Univ Bergen, Dept Global Publ Hlth & Primary Care, N-5018 Bergen, Norway.
[Morken, N-H] Univ Bergen, Dept Clin Sci, N-5018 Bergen, Norway.
[Skjaerven, R.] Norwegian Inst Publ Hlth, Bergen, Norway.
[Wilcox, A. J.] NIEHS, Epidemiol Branch, NIH, Durham, NC USA.
RP Morken, NH (reprint author), Univ Bergen, Dept Global Publ Hlth & Primary Care, Kalfarveien 31, N-5018 Bergen, Norway.
EM nils-halvdan.morken@kk.uib.no
OI Wilcox, Allen/0000-0002-3376-1311
FU University of Bergen; Unger-Vetlesen Medical Foundation
FX NHM was funded with grants from the University of Bergen and the
Unger-Vetlesen Medical Foundation. The funding organisation had no
influence on planning or performing the project, interpretation of data,
or preparation of the article.
NR 23
TC 0
Z9 0
U1 2
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1470-0328
EI 1471-0528
J9 BJOG-INT J OBSTET GY
JI BJOG
PD NOV
PY 2015
VL 122
IS 12
BP 1674
EP 1681
DI 10.1111/1471-0528.13022
PG 8
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA CU7NY
UT WOS:000363729300048
PM 25135694
ER
PT J
AU Pillai, VC
Han, KL
Beigi, RH
Hankins, GD
Clark, S
Hebert, MF
Easterling, TR
Zajicek, A
Ren, ZX
Caritis, SN
Venkataramanan, R
AF Pillai, Venkateswaran C.
Han, Kelong
Beigi, Richard H.
Hankins, Gary D.
Clark, Shannon
Hebert, Mary F.
Easterling, Thomas R.
Zajicek, Anne
Ren, Zhaoxia
Caritis, Steve N.
Venkataramanan, Raman
TI Population pharmacokinetics of oseltamivir in non-pregnant and pregnant
women
SO BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
LA English
DT Article
DE oseltamivir; population pharmacokinetics; pregnancy
ID VIRUS-INFECTION; RO 64-0802; INFLUENZA; H1N1; INFANTS; DEATHS; DRUG
AB AimsPhysiological changes in pregnancy are expected to alter the pharmacokinetics of various drugs. The objective of this study was to evaluate systematically the pharmacokinetics of oseltamivir (OS), a drug used in the treatment of influenza during pregnancy.
MethodsA multicentre steady-state pharmacokinetic study of OS was performed in 35 non-pregnant and 29 pregnant women. Plasma concentration-time profiles were analyzed using both non-compartmental and population pharmacokinetic modelling (pop PK) and simulation approaches. A one compartment population pharmacokinetic model with first order absorption and elimination adequately described the pharmacokinetics of OS.
ResultsThe systemic exposure of oseltamivir carboxylate (OC, active metabolite of OS) was reduced approximately 30 (19-36)% (P<0.001) in pregnant women. Pregnancy significantly (P<0.001) influenced the clearance (CL/F) and volume of distribution (V/F) of OC. Both non-compartmental and population pharmacokinetic approaches documented approximately 45 (23-62)% increase in clearance (CL/F) of OC during pregnancy.
ConclusionBased on the decrease in exposure of the active metabolite, the currently recommended doses of OS may need to be increased modestly in pregnant women in order to achieve comparable exposure with that of non-pregnant women.
C1 [Pillai, Venkateswaran C.; Venkataramanan, Raman] Univ Pittsburgh, Sch Pharm, Dept Pharmaceut Sci, Pittsburgh, PA 15261 USA.
[Han, Kelong] Genentech Inc, Clin Pharmacol, San Francisco, CA USA.
[Beigi, Richard H.; Caritis, Steve N.] Univ Pittsburgh, Med Ctr, Magee Womens Hosp, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA 15260 USA.
[Hankins, Gary D.; Clark, Shannon] Univ Texas Med Branch, Dept Obstet & Gynecol, Austin, TX USA.
[Hebert, Mary F.; Easterling, Thomas R.] Univ Washington, Dept Pharm & Obstet & Gynecol, Seattle, WA 98195 USA.
[Zajicek, Anne; Ren, Zhaoxia] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Obstet & Pediat Pharmacol & Therapeut Branch, Bethesda, MD USA.
RP Venkataramanan, R (reprint author), Univ Pittsburgh, Sch Pharm, Dept Pharmaceut Sci, 718 Salk Hall,3501 Terrace St, Pittsburgh, PA 15261 USA.
EM rv@pitt.edu
FU Obstetric Pharmacology Research Unit Network, Eunice Kennedy Shriver
National Institute of Child Health and Human Development (NICHD) [5U10
HD 047905, U10 HD047892, 3U10 HD047891-05S2]
FX This work is funded by grants (5U10 HD 047905, U10 HD047892 and 3U10
HD047891-05S2) from Obstetric Pharmacology Research Unit Network, Eunice
Kennedy Shriver National Institute of Child Health and Human Development
(NICHD). We acknowledge the clinical staff (Donna Deangetlis and Dawn
Fisher from University of Pittsburgh Medical Center, Holly West from
University of Texas Medical Branch, Claudine Hernandez and Karen Hays
from University of Washington) who helped for study conduct/data
collection for this research. The study team also acknowledges Roche
Pharmaceuticals for the logistic support for bio-analysis of oseltamivir
and oseltamivir carboxylate.
NR 27
TC 1
Z9 1
U1 1
U2 8
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0306-5251
EI 1365-2125
J9 BRIT J CLIN PHARMACO
JI Br. J. Clin. Pharmacol.
PD NOV
PY 2015
VL 80
IS 5
BP 1042
EP 1050
DI 10.1111/bcp.12691
PG 9
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA CU9UF
UT WOS:000363890400013
PM 26040405
ER
PT J
AU Ayanwuyi, LO
Stopponi, S
Ubaldi, M
Cippitelli, A
Nasuti, C
Damadzic, R
Heilig, M
Schank, J
Cheng, KJ
Rice, KC
Ciccocioppo, R
AF Ayanwuyi, Lydia O.
Stopponi, Serena
Ubaldi, Massimo
Cippitelli, Andrea
Nasuti, Cinzia
Damadzic, Ruslan
Heilig, Markus
Schank, Jesse
Cheng, Kejun
Rice, Kenner C.
Ciccocioppo, Roberto
TI Neurokinin 1 receptor blockade in the medial amygdala attenuates alcohol
drinking in rats with innate anxiety but not in Wistar rats
SO BRITISH JOURNAL OF PHARMACOLOGY
LA English
DT Article
ID CORTICOTROPIN-RELEASING-FACTOR; CENTRAL-NERVOUS-SYSTEM; SUBSTANCE-P
RECEPTOR; PREFERRING MSP RATS; NORADRENERGIC MECHANISMS; VOLUNTARY
CONSUMPTION; SEEKING BEHAVIOR; ADDICTION FOCUS; NK-1 RECEPTOR; NK1
RECEPTOR
AB Background and PurposeSubstance P and its preferred neurokinin receptor NK1 have been implicated in stress and anxiety and have been proposed as possible therapeutic targets for the treatment of anxiety/depression. Attention is also being focused on the role this neuropeptide system may play in drug addiction, because stress-related mechanisms promote drug abuse.
Experimental ApproachThe effects of the rat-specific NK1 receptor antagonist, L822429, on alcohol intake and seeking behaviour was investigated in genetically selected Marchigian Sardinian alcohol preferring rats. These rats demonstrate an anxious phenotype and are highly sensitive to stress and stress-induced drinking.
Key ResultsSystemic administration of L822429 significantly reduced operant alcohol self-administration in Marchigian Sardinian alcohol preferring rats, but did not reduce alcohol self-administration in stock Wistar rats. NK1 receptor antagonism also attenuated yohimbine-induced reinstatement of alcohol seeking at all doses tested but had no effect on cue-induced reinstatement of alcohol seeking. L822429 reduced operant alcohol self-administration when injected into the lateral cerebroventricles or the medial amygdala. L822429 injected into the medial amygdala also significantly reduced anxiety-like behaviour in the elevated plus maze test. No effects on alcohol intake were observed following injection of L822429 into the dorsal or the ventral hippocampus. Conclusions and Implications Our results suggest that NK1 receptor antagonists may be useful for the treatment of alcohol addiction associated with stress or comorbid anxiety disorders. The medial amygdala appears to be an important brain site of action of NK1 receptor antagonism.
C1 [Ayanwuyi, Lydia O.; Stopponi, Serena; Ubaldi, Massimo; Cippitelli, Andrea; Nasuti, Cinzia; Ciccocioppo, Roberto] Univ Camerino, Sch Pharm, Pharmacol Unit, I-62032 Camerino, MC, Italy.
[Damadzic, Ruslan; Heilig, Markus] NIAAA, Lab Clin & Translat Studies, NIH, Bethesda, MD 20892 USA.
[Schank, Jesse] Univ Georgia, Coll Vet Med, Dept Physiol & Pharmacol, Athens, GA 30602 USA.
[Cheng, Kejun; Rice, Kenner C.] NIDA, Drug Design & Synth Sect, Chem Biol Res Branch, Bethesda, MD 20892 USA.
[Cheng, Kejun; Rice, Kenner C.] NIAAA, NIH, Bethesda, MD USA.
RP Ciccocioppo, R (reprint author), Univ Camerino, Sch Pharm, Pharmacol Unit, Via Madonna Carceri 9, I-62032 Camerino, MC, Italy.
EM roberto.ciccocioppo@unicam.it
RI nasuti, cinzia/F-5212-2011;
OI nasuti, cinzia/0000-0002-4470-7345; Ubaldi, Massimo/0000-0002-4089-2483
FU NIH [AA014351, AA017447]; NIH Intramural Research Programs of the
National Institute on Drug Abuse (NIDA); National Institute of Alcohol
Abuse and Alcoholism
FX This study was supported by NIH grants nos. AA014351 and AA017447. A
portion of this work was supported by the NIH Intramural Research
Programs of the National Institute on Drug Abuse (NIDA) and the National
Institute of Alcohol Abuse and Alcoholism. We are thankful to Alfredo
Fiorelli for technical support as well as Rina Righi and Mariangela
Fiorelli for animal care.
NR 62
TC 1
Z9 2
U1 1
U2 5
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 NOV
PY 2015
VL 172
IS 21
BP 5136
EP 5146
DI 10.1111/bph.13280
PG 11
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA CU9XS
UT WOS:000363900900009
PM 26275374
ER
PT J
AU Wei, GS
Coady, SA
Reis, JP
Carnethon, MR
Coresh, J
D'Agostino, RB
Goff, DC
Jacobs, DR
Selvin, E
Fox, CS
AF Wei, Gina S.
Coady, Sean A.
Reis, Jared P.
Carnethon, Mercedes R.
Coresh, Josef
D'Agostino, Ralph B., Sr.
Goff, David C., Jr.
Jacobs, David R., Jr.
Selvin, Elizabeth
Fox, Caroline S.
TI Duration and Degree of Weight Gain and Incident Diabetes in Younger
Versus Middle-Aged Black and White Adults: ARIC, CARDIA, and the
Framingham Heart Study
SO DIABETES CARE
LA English
DT Article
ID BODY-MASS INDEX; IMPAIRED GLUCOSE-TOLERANCE; ATHEROSCLEROSIS RISK;
UNITED-STATES; INSULIN-RESISTANCE; AFRICAN-AMERICANS; OBESITY; MELLITUS;
DISEASE; COMMUNITIES
AB OBJECTIVE
To determine whether duration and degree of weight gain are differentially associated with diabetes risk in younger versus middle-aged black and white adults.
RESEARCH DESIGN AND METHODS
We combined data from three cohort studies: Atherosclerosis Risk in Communities (ARIC), Coronary Artery Risk Development in Young Adults (CARDIA), and the Framingham Heart Study. A total of 17,404 participants (56% women; 21% black) were stratified by baseline age (younger: >= 30 and <45 years; middle-aged: >= 45 and <60 years) and examined for incident diabetes (median follow-up 9 years). Duration and degree of gain in BMI were calculated as "BMI-years" above one's baseline BMI.
RESULTS
Diabetes incidence per 1,000 person-years in the younger and middle-aged groups was 7.2 (95% CI 5.7, 8.7) and 24.4 (22.0, 26.8) in blacks, respectively, and 3.4 (2.8, 4.0) and 10.5 (9.9, 11.2) in whites, respectively. After adjusting for sex, baseline BM I and other cardiometabolic factors, and age and race interaction terms, gains in BMI-years were associated with higher risk of diabetes in the younger compared with middle-aged groups: hazard ratios for 1-unit increase in log BMI-years in younger versus middle-aged blacks were 1.18 (P = 0.02) and 1.02 (P = 0.39), respectively (P for interaction by age-group = 0.047), and in whites were 1.35 (P < 0.001) and 1.11 (P < 0.001), respectively (P for interaction by age-group = 0.008).
CONCLUSIONS
Although middle-aged adults have higher rates of diabetes, younger adults are at greater relative risk of developing diabetes for a given level of duration and degree of weight gain.
C1 [Wei, Gina S.; Coady, Sean A.; Reis, Jared P.] NHLBI, Div Cardiovasc Sci, NIH, Bethesda, MD 20892 USA.
[Carnethon, Mercedes R.] Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA.
[Coresh, Josef; Selvin, Elizabeth] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Coresh, Josef; Selvin, Elizabeth] Johns Hopkins Bloomberg Sch Publ Hlth, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD USA.
[Coresh, Josef; Selvin, Elizabeth] Johns Hopkins Univ, Dept Med, Div Gen Internal Med, Baltimore, MD USA.
[D'Agostino, Ralph B., Sr.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA.
[Goff, David C., Jr.] Colorado Sch Publ Hlth, Off Dean, Aurora, CO USA.
[Jacobs, David R., Jr.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA.
[Fox, Caroline S.] NHLBI, Framingham Heart Study, Ctr Populat Studies, Bethesda, MD 20892 USA.
RP Wei, GS (reprint author), NHLBI, Div Cardiovasc Sci, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM weig@nhlbi.nih.gov
FU National Heart, Lung, and Blood Institute (NHLBI) [HHSN268201100005C,
HHSN268201100006C, HHSN268201100007C, HHSN268201100008C,
HHSN268201100009C, HHSN268201100010C, HHSN268201100011C,
HHSN268201100012C]; NHLBI [HHSN268201300025C, HHSN268201300026C,
HHSN268201300027C, HHSN268201300028C, HHSN268201300029C,
HHSN268200900041C, AG0005]; Intramural Research Program of the National
Institute on Aging (NIA); NIA [AG0005]; Boston University [N01-HC-25195]
FX The ARIC study is carried out as a collaborative study supported by
National Heart, Lung, and Blood Institute (NHLBI) contracts
(HHSN268201100005C, HHSN268201100006C, HHSN268201100007C,
HHSN268201100008C, HHSN268201100009C, HHSN268201100010C,
HHSN268201100011C, and HHSN268201100012C). CARDIA is supported by NHLBI
contracts HHSN268201300025C, HHSN268201300026C, HHSN268201300027C,
HHSN268201300028C, HHSN268201300029C, and HHSN268200900041C; the
Intramural Research Program of the National Institute on Aging (NIA);
and an intra-agency agreement between the NIA and NHLBI (AG0005). The
Framingham Heart Study is conducted and supported by the NHLBI in
collaboration with Boston University (contract N01-HC-25195).
NR 34
TC 3
Z9 3
U1 0
U2 4
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0149-5992
EI 1935-5548
J9 DIABETES CARE
JI Diabetes Care
PD NOV
PY 2015
VL 38
IS 11
BP 2042
EP 2049
DI 10.2337/dc14-2770
PG 8
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA CV5WQ
UT WOS:000364342500022
PM 26358286
ER
PT J
AU Esparza-Romero, J
Valencia, ME
Urquidez-Romero, R
Chaudhari, LS
Hanson, RL
Knowler, WC
Ravussin, E
Bennett, PH
Schulz, LO
AF Esparza-Romero, Julian
Valencia, Mauro E.
Urquidez-Romero, Rene
Chaudhari, Lisa S.
Hanson, Robert L.
Knowler, William C.
Ravussin, Eric
Bennett, Peter H.
Schulz, Leslie O.
TI Environmentally Driven Increases in Type 2 Diabetes and Obesity in Pima
Indians and Non-Pimas in Mexico Over a 15-Year Period: The Maycoba
Project
SO DIABETES CARE
LA English
DT Article
ID RISK-FACTORS; PHYSICAL-ACTIVITY; PREVALENCE; GLUCOSE
AB OBJECTIVE
The global epidemics of type 2 diabetes and obesity have been attributed to the interaction between lifestyle changes and genetic predisposition to these diseases. We compared the prevalences of type 2 diabetes and obesity in Mexican Pima Indians, presumed to have a high genetic predisposition to these diseases, to those in their non-Pima neighbors, both of whom over a 15-year period experienced a transition from a traditional to a more modern lifestyle.
RESEARCH DESIGN AND METHODS
Prevalence of diabetes, impaired fasting glucose, impaired glucose tolerance, and obesity in Mexican Pimas (n = 359) and non-Pima Mexicans (n = 251) were determined in 2010 using methods identical to those used in 1995.
RESULTS
During this 15-year period, age-adjusted diabetes prevalence was unchanged in Pima men (5.8% in 1995 vs. 6.1% in 2010) yet increased in non-Pima men from 0.0 to 8.6% (P < 0.05). Diabetes prevalence tended to increase in both Pima women (9.4 vs. 13.4%) and non-Pima women (4.8 vs. 9.5%). Age-adjusted prevalence of obesity increased significantly in all groups (6.6 vs. 15.7% in Pima men; 8.5 vs. 20.5% in non-Pima men; 18.9. vs 36.3% in Pima women; 29.5 vs. 42.9% in non-Pima women).
CONCLUSIONS
Type 2 diabetes prevalence increased between 1995 and 2010 in non-Pima men, and to a lesser degree in women of both groups, but it did not increase in Pima men. Prevalence of obesity increased among Pimas and non-Pimas of both sexes. These changes occurred concomitantly with an environmental transition from a traditional to a more modernized lifestyle.
C1 [Esparza-Romero, Julian; Valencia, Mauro E.; Urquidez-Romero, Rene] Ctr Invest Alimentac & Desarrollo AC, Dept Nutr Publ & Salud, Coordinac Nutr, Hermosillo, Sonora, Mexico.
[Chaudhari, Lisa S.; Schulz, Leslie O.] No Arizona Univ, Coll Hlth & Human Serv, Flagstaff, AZ 86011 USA.
[Hanson, Robert L.; Knowler, William C.; Bennett, Peter H.] Natl Inst Diabet & Digest & Kidney Dis, Phoenix Epidemiol & Clin Res Branch, NIH, Phoenix, AZ USA.
[Ravussin, Eric] Pennington Biomed Res Ctr, Baton Rouge, LA 70808 USA.
RP Schulz, LO (reprint author), No Arizona Univ, Coll Hlth & Human Serv, Flagstaff, AZ 86011 USA.
EM rhanson@phx.niddk.nih.gov; leslie.schulz@nau.edu
FU U.S. National Institutes of Health [1R01DK082568-01A1]; U.S. National
Institute of Diabetes and Digestive and Kidney Diseases
FX The Maycoba Project was funded by the U.S. National Institutes of Health
(grant 1R01DK082568-01A1 to L.O.S.). The study was also supported in
part by the intramural research program of the U.S. National Institute
of Diabetes and Digestive and Kidney Diseases.
NR 21
TC 3
Z9 3
U1 2
U2 8
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0149-5992
EI 1935-5548
J9 DIABETES CARE
JI Diabetes Care
PD NOV
PY 2015
VL 38
IS 11
BP 2075
EP 2082
DI 10.2337/dc15-0089
PG 8
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA CV5WQ
UT WOS:000364342500026
PM 26246457
ER
PT J
AU Sharma, V
Khurana, S
Kubben, N
Abdelmohsen, K
Oberdoerffer, P
Gorospe, M
Misteli, T
AF Sharma, Vivek
Khurana, Simran
Kubben, Nard
Abdelmohsen, Kotb
Oberdoerffer, Philipp
Gorospe, Myriam
Misteli, Tom
TI A BRCA1-interacting lncRNA regulates homologous recombination
SO EMBO REPORTS
LA English
DT Article
DE BRCA1; hnRNPUL1; p53; RAP80; repair
ID DNA-DAMAGE RESPONSE; LONG NONCODING RNA; DOUBLE-STRAND BREAKS;
GENE-EXPRESSION; END RESECTION; CELL-CYCLE; REPAIR; P53; CHROMATIN;
COMPLEX
AB Long non-coding RNAs (lncRNAs) are important players in diverse biological processes. Upon DNA damage, cells activate a complex signaling cascade referred to as the DNA damage response (DDR). Using a microarray screen, we identify here a novel lncRNA, DDSR1 (DNA damage-sensitive RNA1), which is induced upon DNA damage. DDSR1 induction is triggered in an ATM-NF-B pathway-dependent manner by several DNA double-strand break (DSB) agents. Loss of DDSR1 impairs cell proliferation and DDR signaling and reduces DNA repair capacity by homologous recombination (HR). The HR defect in the absence of DDSR1 is marked by aberrant accumulation of BRCA1 and RAP80 at DSB sites. In line with a role in regulating HR, DDSR1 interacts with BRCA1 and hnRNPUL1, an RNA-binding protein involved in DNA end resection. Our results suggest a role for the lncRNA DDSR1 in modulating DNA repair by HR.
C1 [Sharma, Vivek; Khurana, Simran; Kubben, Nard; Oberdoerffer, Philipp; Misteli, Tom] Natl Canc Inst, NIH, Bethesda, MD 20892 USA.
[Abdelmohsen, Kotb; Gorospe, Myriam] NIA, NIH, Baltimore, MD 21224 USA.
RP Sharma, V (reprint author), Natl Canc Inst, NIH, Bethesda, MD 20892 USA.
EM viveksharmabt@gmail.com; mistelit@mail.nih.gov
FU Khorana Nirenberg Fellowship; Intramural Research Program of the
National Institutes of Health (NIH); NIA; NCI Center for Cancer Research
FX We thank David Sun, Xiaolin Wu, Li Jia, and Anand Merchant for
Microarray experiments and analysis; Katherine McKinnon for help with
FACS experiments; Tatiana Karpova (NCI Fluorescence Imaging Microscopy
Facility) for help with microscopy; Murali Palangat for FISH imaging;
Andy Tran for ssBrDU/cyclin A staining analysis; and Sudipto Das and
Thorkell Anderson for help with mass spectrometry experiments. The
authors would like to thank Misteli Lab members for helpful feedback and
discussions. This research was supported by the Intramural Research
Program of the National Institutes of Health (NIH), NIA, NCI Center for
Cancer Research, and by a Khorana Nirenberg Fellowship to VS.
NR 57
TC 7
Z9 8
U1 3
U2 11
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1469-221X
EI 1469-3178
J9 EMBO REP
JI EMBO Rep.
PD NOV
PY 2015
VL 16
IS 11
BP 1520
EP 1534
PG 15
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA CV5NX
UT WOS:000364318900016
PM 26412854
ER
PT J
AU Lhatoo, S
Noebels, J
Whittemore, V
AF Lhatoo, Samden
Noebels, Jeffrey
Whittemore, Vicky
CA NINDS Ctr SUDEP Res
TI Sudden unexpected death in epilepsy: Identifying risk and preventing
mortality
SO EPILEPSIA
LA English
DT Article
DE Cardiorespiratory; Autonomic dysfunction; Imaging; Genetics; Induced
pluripotent stem cell; Neuropathology
ID POSTICTAL EEG SUPPRESSION; TEMPORAL-LOBE EPILEPSY; UNEXPLAINED DEATH;
RESPIRATORY DYSFUNCTION; CONVULSIVE SEIZURES; SUDEP; MECHANISMS;
PATIENT; NEURONS; PATHWAY
AB Premature death among individuals with epilepsy is higher than in the general population, and sudden unexpected death is the most common cause of this mortality. A new multisite collaborative research consortium, the Center for sudden unexpected death in epilepsy (SUDEP) Research (CSR), has received major funding from the National Institutes of Health (NIH) to examine the possible biologic mechanisms underlying this potentially preventable comorbidity and develop predictive biomarkers for interventions that could lower SUDEP incidence. This inaugural report describes the structure of the CSR, its priorities for human and experimental research, and the strategic collaborations and advanced tools under development to reduce this catastrophic outcome of epilepsy. The CSR Partners Program will work closely with committed volunteer agencies, industry, and academic institutions to accelerate and communicate these advances to the professional and lay community.
C1 [Lhatoo, Samden] Case Western Reserve Univ, Neurol, Cleveland, OH 44106 USA.
[Noebels, Jeffrey] Baylor Coll Med, Neurol, Houston, TX 77030 USA.
[Whittemore, Vicky] NINDS, Epilepsy Channels, Synapses & Circuits, NIH, Rockville, MD USA.
RP Noebels, J (reprint author), Baylor Coll Med, Neurol, Houston, TX 77030 USA.
EM jnoebels@bcm.edu
OI Noebels, Jeffrey /0000-0002-2887-0839
FU NINDS [U01-NS090407, U01-NS090408, U01-NS090415, U01-NS090364,
U01-NS090340, U01-NS090406, U01-NS090362, U01-NS090414, U01-NS090405]
FX The Center for SUDEP Research is supported by NINDS grants U01-NS090407,
U01-NS090408, U01-NS090415, U01-NS090364, U01-NS090340, U01-NS090406,
U01-NS090362, U01-NS090414, and U01-NS090405.
NR 45
TC 7
Z9 7
U1 2
U2 9
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0013-9580
EI 1528-1167
J9 EPILEPSIA
JI Epilepsia
PD NOV
PY 2015
VL 56
IS 11
BP 1700
EP 1706
DI 10.1111/epi.13134
PG 7
WC Clinical Neurology
SC Neurosciences & Neurology
GA CU9RZ
UT WOS:000363884100011
PM 26494436
ER
PT J
AU Lemire, M
Qu, CH
Loo, LWM
Zaidi, SHE
Wang, H
Berndt, SI
Bezieau, S
Brenner, H
Campbell, PT
Chan, AT
Chang-Claude, J
Du, MM
Edlund, CK
Gallinger, S
Haile, RW
Harrison, TA
Hoffmeister, M
Hopper, JL
Hou, LF
Hsu, L
Jacobs, EJ
Jenkins, MA
Jeon, J
Kury, S
Li, L
Lindor, NM
Newcomb, PA
Potter, JD
Rennert, G
Rudolph, A
Schoen, RE
Schumacher, FR
Seminara, D
Severi, G
Slattery, ML
White, E
Woods, MO
Cotterchio, M
Le Marchand, L
Casey, G
Gruber, SB
Peters, U
Hudson, TJ
AF Lemire, Mathieu
Qu, Conghui
Loo, Lenora W. M.
Zaidi, Syed H. E.
Wang, Hansong
Berndt, Sonja I.
Bezieau, Stephane
Brenner, Hermann
Campbell, Peter T.
Chan, Andrew T.
Chang-Claude, Jenny
Du, Mengmeng
Edlund, Christopher K.
Gallinger, Steven
Haile, Robert W.
Harrison, Tabitha A.
Hoffmeister, Michael
Hopper, John L.
Hou, Lifang
Hsu, Li
Jacobs, Eric J.
Jenkins, Mark A.
Jeon, Jihyoun
Kuery, Sebastien
Li, Li
Lindor, Noralane M.
Newcomb, Polly A.
Potter, John D.
Rennert, Gad
Rudolph, Anja
Schoen, Robert E.
Schumacher, Fredrick R.
Seminara, Daniela
Severi, Gianluca
Slattery, Martha L.
White, Emily
Woods, Michael O.
Cotterchio, Michelle
Le Marchand, Loic
Casey, Graham
Gruber, Stephen B.
Peters, Ulrike
Hudson, Thomas J.
TI A genome-wide association study for colorectal cancer identifies a risk
locus in 14q23.1
SO HUMAN GENETICS
LA English
DT Article
ID SOCIETY-TASK-FORCE; SUSCEPTIBILITY LOCI; ER STRESS; METAANALYSIS;
TUMORS; CELLS; SCAN; SURVEILLANCE; VARIANTS; 8Q24
AB Over 50 loci associated with colorectal cancer (CRC) have been uncovered by genome-wide association studies (GWAS). Identifying additional loci has the potential to help elucidate aspects of the underlying biological processes leading to better understanding of the pathogenesis of the disease. We re-evaluated a GWAS by excluding controls that have family history of CRC or personal history of colorectal polyps, as we hypothesized that their inclusion reduces power to detect associations. This is supported empirically and through simulations. Two-phase GWAS analysis was performed in a total of 16,517 cases and 14,487 controls. We identified rs17094983, a SNP associated with risk of CRC [p = 2.5 x 10(-10); odds ratio estimated by re-including all controls (OR) = 0.87, 95 % confidence interval (CI) 0.83-0.91; minor allele frequency (MAF) = 13 %]. Results were replicated in samples of African descent (1894 cases and 4703 controls; p = 0.01; OR = 0.86, 95 % CI 0.77-0.97; MAF = 16 %). Gene expression data in 195 colon adenocarcinomas and 59 normal colon tissues from two different studies revealed that this locus has genotypes that are associated with RTN1 (Reticulon 1) expression (p = 0.001), a protein-coding gene involved in survival and proliferation of cancer cells which is highly expressed in normal colon tissues but has significantly reduced expression in tumor cells (p = 1.3 x 10(-8)).
C1 [Lemire, Mathieu; Zaidi, Syed H. E.; Hudson, Thomas J.] Ontario Inst Canc Res, MaRS Ctr, Toronto, ON M5G 0A3, Canada.
[Qu, Conghui; Harrison, Tabitha A.; Hsu, Li; Jeon, Jihyoun; Newcomb, Polly A.; Potter, John D.; White, Emily; Peters, Ulrike] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA.
[Loo, Lenora W. M.; Wang, Hansong; Le Marchand, Loic] Univ Hawaii, Ctr Canc, Program Epidemiol, Honolulu, HI 96822 USA.
[Berndt, Sonja I.] NCI, Occupat & Environm Epidemiol Branch, Bethesda, MD 20892 USA.
[Bezieau, Stephane; Kuery, Sebastien] CHU Nantes, Serv Genet Med, F-44035 Nantes 01, France.
[Bezieau, Stephane] Univ Nantes, Fac Med, EA 4273, Nantes, France.
[Brenner, Hermann; Hoffmeister, Michael] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany.
[Brenner, Hermann] German Canc Consortium DKTK, Heidelberg, Germany.
[Brenner, Hermann] German Canc Res Ctr, Div Prevent Oncol, Heidelberg, Germany.
[Campbell, Peter T.; Jacobs, Eric J.] Amer Canc Soc, Atlanta, GA 30329 USA.
[Chan, Andrew T.] Massachusetts Gen Hosp, Div Gastroenterol, Boston, MA 02114 USA.
[Chan, Andrew T.] Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA.
[Chang-Claude, Jenny] German Canc Res Ctr, Div Canc Epidemiol, Unit Genet Epidemiol, Heidelberg, Germany.
[Edlund, Christopher K.; Schumacher, Fredrick R.; Casey, Graham; Gruber, Stephen B.] Univ So Calif, Norris Comprehens Canc Ctr, Keck Sch Med, Dept Prevent Med, Los Angeles, CA USA.
[Gallinger, Steven] Samuel Lunenfeld Res Inst, Toronto, ON M5S 1X5, Canada.
[Gallinger, Steven] Toronto Gen Hosp, Div Gen Surg, Toronto, ON M5G 2C4, Canada.
Stanford Univ, Dept Med, Div Oncol, Stanford, CA 94305 USA.
Univ Melbourne, Ctr Biostat & Epidemiol, Sch Populat & Global Hlth, Melbourne, Vic, Australia.
[Hou, Lifang] Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Evanston, IL USA.
[Hou, Lifang] Northwestern Univ, Feinberg Sch Med, Robert H Lurie Comprehens Canc Ctr, Evanston, IL USA.
[Hsu, Li] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Li, Li] Case Western Reserve Univ, Case Comprehens Canc Ctr, Cleveland, OH 44106 USA.
[Li, Li] Case Western Reserve Univ, Swetland Ctr Environm Hlth, Cleveland, OH 44106 USA.
[Lindor, Noralane M.] Mayo Clin, Dept Hlth Sci Res, Scottsdale, AZ USA.
[Newcomb, Polly A.; Potter, John D.; White, Emily] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA.
[Potter, John D.] Massey Univ, Ctr Publ Hlth Res, Wellington, New Zealand.
[Rennert, Gad] Carmel Hosp, Dept Community Med & Epidemiol, Haifa, Israel.
[Rennert, Gad] Natl Canc Control Ctr, Clalit Hlth Serv, Haifa, Israel.
[Rennert, Gad] Technion Israel Inst Technol, Bruce Rappaport Fac Med, IL-31096 Haifa, Israel.
[Schoen, Robert E.] Univ Pittsburgh, Med Ctr, Div Gastroenterol Hepatol & Nutr, Pittsburgh, PA USA.
[Seminara, Daniela] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Severi, Gianluca] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic, Australia.
[Severi, Gianluca] Human Genet Fdn HuGeF, Turin, Italy.
[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 A1B 3V6, Canada.
[Cotterchio, Michelle] Univ Toronto, Canc Care Ontario, Toronto, ON, Canada.
[Gruber, Stephen B.] Univ So Calif, Norris Comprehens Canc Ctr, Keck Sch Med, Dept Med, Los Angeles, CA USA.
[Peters, Ulrike] Univ Washington, Sch Publ Hlth, Seattle, WA 98195 USA.
[Hudson, Thomas J.] Univ Toronto, Dept Med Biophys, Toronto, ON M5S 1A1, Canada.
[Hudson, Thomas J.] Univ Toronto, Dept Mol Genet, Toronto, ON M5S 1A1, Canada.
RP Lemire, M (reprint author), Ontario Inst Canc Res, MaRS Ctr, 661 Univ Ave,Suite 510, Toronto, ON M5G 0A3, Canada.
EM mathieu.lemire@oicr.on.ca; cqu@fredhutch.org; lloo@cc.hawaii.edu;
hassan.zaidi@oicr.on.ca; hwang@cc.hawaii.edu; berndts@mail.nih.gov;
stephane.bezieau@univ-nantes.fr; h.brenner@dkfz.de;
Peter.Campbell@cancer.org; achan@mgh.harvard.edu;
j.chang-claude@dkfz.de; mdu@fredhutch.org; cedlund@usc.edu;
Steven.Gallinger@uhn.on.ca; rhaile@stanford.edu; tharriso@fredhutch.org;
m.hoffmeister@dkfz.de; j.hopper@unimelb.edu.au; l-hou@northwestern.edu;
lih@fredhutch.org; Eric.Jacobs@cancer.org; m.jenkins@unimelb.edu.au;
jhjeon@fredhutch.org; sebastien.kury@chu-nantes.fr; lxl62@cwru.edu;
nlindor@mayo.edu; pnewcomb@fredhutch.org; jpotter@fredhutch.org;
rennert@tx.technion.ac.il; a.rudolph@dkfz.de; rschoen@pitt.edu;
fschumac@usc.edu; seminard@mail.nih.gov;
Gianluca.Severi@cancervic.org.au; marty.slattery@hsc.utah.edu;
ewhite@fredhutch.org; mwoods@mun.ca;
michelle.cotterchio@cancercare.on.ca; loic@cc.hawaii.edu;
gcasey@usc.edu; sgruber@usc.edu; upeters@fredhutch.org;
tom.hudson@oicr.on.ca
RI Jenkins, Mark/P-7803-2015; KURY, Sebastien/G-5971-2015; Gallinger,
Steven/E-4575-2013; Brenner, Hermann/B-4627-2017;
OI Jenkins, Mark/0000-0002-8964-6160; KURY, Sebastien/0000-0001-5497-0465;
Brenner, Hermann/0000-0002-6129-1572; Potter, John/0000-0001-5439-1500;
Hoffmeister, Michael/0000-0002-8307-3197
FU American Cancer Society (ACS); Centers for Disease Control and
Prevention National Program of Cancer Registries; National Cancer
Institute Surveillance Epidemiology and End Results program
FX CANCER PREVENTION STUDY II: CPS-II is supported by the American Cancer
Society (ACS). We would like to thank the CPS-II participants and the
CPS-II Study Management Group for their invaluable contributions to this
research. The authors would also like to acknowledge the contribution to
this study from central cancer registries supported through the Centers
for Disease Control and Prevention National Program of Cancer
Registries, and cancer registries supported by the National Cancer
Institute Surveillance Epidemiology and End Results program.
NR 37
TC 5
Z9 5
U1 1
U2 10
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0340-6717
EI 1432-1203
J9 HUM GENET
JI Hum. Genet.
PD NOV
PY 2015
VL 134
IS 11-12
BP 1249
EP 1262
DI 10.1007/s00439-015-1598-6
PG 14
WC Genetics & Heredity
SC Genetics & Heredity
GA CV0VZ
UT WOS:000363973000008
PM 26404086
ER
PT J
AU Lu, JH
Sun, PD
AF Lu, Jinghua
Sun, Peter D.
TI Structural mechanism of high affinity FcRI recognition of immunoglobulin
G
SO IMMUNOLOGICAL REVIEWS
LA English
DT Review
DE CD64; antibody recognition; high affinity Fc gamma receptor;
FcgammaRI-Fc complex structure; glycan recognition by Fc receptor
ID GAMMA RECEPTOR; HUMAN IGG1; CRYSTAL-STRUCTURE; THERAPEUTIC ANTIBODIES;
EFFECTOR FUNCTIONS; BINDING; COMPLEX; FRAGMENT; CANCER; FUCOSE
AB Antibody-based immunotherapies are becoming powerful means of modern medicine for treating cancers and autoimmune diseases. The increasing popularity of antibody-based treatment demands a better understanding of antibody functions and in particular, their interaction with Fc receptors as effectiveness of antibodies often depends on their ability to activate or avoid effector cell functions through Fc receptors. Until recently, our understanding of antibody recognition by Fc receptors is based on the structures of low affinity Fc receptor in complex with Fc. These structural studies provided significant insights to our understanding of how an IgG antibody generally docks on Fc receptor and the requirement of immune complex formation for effector cell activations. They are less informative, however, to the molecular forces underlying the vast different affinities between antibodies and their Fc receptors. Recently, the structure of the high affinity FcRI in complex with IgG-Fc has been determined. This review will focus on the knowledge learned from the high affinity complex structural work and a potential receptor-glycan interaction as an important contribution to the receptor affinity.
C1 [Lu, Jinghua; Sun, Peter D.] NIAID, Struct Immunol Sect, Immunogenet Lab, NIH, Rockville, MD 20852 USA.
RP Sun, PD (reprint author), NIAID, Struct Immunol Sect, Immunogenet Lab, NIH, 12441 Parklawn Dr, Rockville, MD 20852 USA.
EM psun@nih.gov
FU Intramural Research program of National Institute of Allergy and
Infectious Diseases, National Institutes of Health
FX The authors acknowledge no potential conflict of interest involved in
this review article. The work was supported by the Intramural Research
program of National Institute of Allergy and Infectious Diseases,
National Institutes of Health.
NR 41
TC 4
Z9 4
U1 1
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0105-2896
EI 1600-065X
J9 IMMUNOL REV
JI Immunol. Rev.
PD NOV
PY 2015
VL 268
IS 1
SI SI
BP 192
EP 200
DI 10.1111/imr.12346
PG 9
WC Immunology
SC Immunology
GA CU9TJ
UT WOS:000363887900013
PM 26497521
ER
PT J
AU Leung, JM
Olivier, KN
Prevots, DR
McDonnell, NB
AF Leung, Janice M.
Olivier, Kenneth N.
Prevots, D. Rebecca
McDonnell, Nazli B.
TI Beyond Marfan: the clinical impact of bronchiectasis and non-tuberculous
mycobacteria in connective tissue diseases
SO INTERNATIONAL JOURNAL OF TUBERCULOSIS AND LUNG DISEASE
LA English
DT Letter
C1 [Leung, Janice M.] Univ British Columbia, Ctr Heart Lung Innovat, Vancouver, BC, Canada.
[Olivier, Kenneth N.] NHLBI, Bethesda, MD 20892 USA.
[Prevots, D. Rebecca] NIAID, Bethesda, MD 20892 USA.
[McDonnell, Nazli B.] Eastern Colorado Hlth Syst, Vet Adm, Denver, CO 80220 USA.
RP McDonnell, NB (reprint author), Eastern Colorado Hlth Syst, Vet Adm, Denver, CO 80220 USA.
EM nazli.mcdonnell@va.gov
FU Intramural NIH HHS
NR 3
TC 1
Z9 1
U1 0
U2 0
PU INT UNION AGAINST TUBERCULOSIS LUNG DISEASE (I U A T L D)
PI PARIS
PA 68 BOULEVARD SAINT-MICHEL,, 75006 PARIS, FRANCE
SN 1027-3719
EI 1815-7920
J9 INT J TUBERC LUNG D
JI Int. J. Tuberc. Lung Dis.
PD NOV
PY 2015
VL 19
IS 11
BP 1409
EP 1409
DI 10.5588/ijtld.15.0597
PG 1
WC Infectious Diseases; Respiratory System
SC Infectious Diseases; Respiratory System
GA CV4XQ
UT WOS:000364270200025
PM 26467599
ER
PT J
AU Arango, CA
Arias, AA
Franco, JL
Orrego, JC
Rojas, JL
Lopez, JA
Patino, PJ
Moncada-Velez, M
Velez, GJ
Grimbacher, B
Woellner, C
Danielian, S
Rosenzweig, S
Walter, JE
Candotti, F
Picard, C
Bustamante, J
Casanova, JL
Germeshausen, M
Hershfield, M
Eraso, RM
Sanchez, IP
Trujillo-Vargas, CM
Builes, LN
Alvarez, JA
AF Andres Arango, Carlos
Augusto Arias, Andres
Luis Franco, Jose
Cesar Orrego, Julio
Lineth Rojas, Jessica
Alvaro Lopez, Juan
Javier Patino, Pablo
Moncada-Velez, Marcela
Jaime Velez, Gabriel
Grimbacher, Bodo
Woellner, Cristina
Danielian, Silvia
Rosenzweig, Sergio
Walter, Jolan E.
Candotti, Fabio
Picard, Capucine
Bustamante, Jacinta
Casanova, Jean Laurent
Germeshausen, Manuela
Hershfield, Michael
Maria Eraso, Ruth
Pilar Sanchez, Isaura
Milena Trujillo-Vargas, Claudia
Natalia Builes, Luz
Armando Alvarez, Jesus
TI Molecular Characterization of Genes Mutated in Patients with Primary
Immunodeficiency Diseases (PIDS) at the Group of Primary
Immunodeficiencies in Colombia 2015: An Update
SO JOURNAL OF CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT 4th Meeting of the Latin-American-Society-for-Immunodeficiencies (LASID)
CY NOV 18-21, 2015
CL Buenos Aires, ARGENTINA
SP Latin Amer Soc Immunodeficiencies
C1 [Andres Arango, Carlos; Augusto Arias, Andres; Luis Franco, Jose; Cesar Orrego, Julio; Lineth Rojas, Jessica; Alvaro Lopez, Juan; Javier Patino, Pablo; Moncada-Velez, Marcela; Jaime Velez, Gabriel; Pilar Sanchez, Isaura; Milena Trujillo-Vargas, Claudia; Armando Alvarez, Jesus] Univ Antioquia, Fac Med, Grp Inmunodeficiencias Primarias, Medellin, Colombia.
[Andres Arango, Carlos; Augusto Arias, Andres; Luis Franco, Jose; Cesar Orrego, Julio; Lineth Rojas, Jessica; Alvaro Lopez, Juan; Javier Patino, Pablo; Moncada-Velez, Marcela; Jaime Velez, Gabriel; Pilar Sanchez, Isaura; Milena Trujillo-Vargas, Claudia; Armando Alvarez, Jesus] Univ Antioquia, Fac Med, Jeffrey Modell Diagnost JMC & Res Ctr, Medellin, Colombia.
[Andres Arango, Carlos; Augusto Arias, Andres; Alvaro Lopez, Juan] Univ Antioquia, Escuela Microbiol, Grp Invest Microbiol Basica & Aplicada MICROBA, Medellin, Colombia.
[Grimbacher, Bodo; Woellner, Cristina] Univ Med Ctr, Ctr Chron Immunodeficiency, Freiburg, Germany.
[Danielian, Silvia] Hosp Pediat Pr Juan P Garrahan, Mol Biol Lab, Buenos Aires, DF, Argentina.
[Rosenzweig, Sergio] NIH, Serv Immunol, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA.
[Rosenzweig, Sergio] NIAID, Primary Immunodeficiency Clin, NIH, Bethesda, MD 20892 USA.
[Walter, Jolan E.] Harvard Univ, Sch Med, Boston Childrens Hosp, Div Immunol, Boston, MA 02115 USA.
[Walter, Jolan E.] Massachusetts Gen Hosp Children, Div Allergy, Pediat Immunodeficiency Program, Boston, MA 02114 USA.
[Candotti, Fabio] NHGRI, NIH, Bethesda, MD 20892 USA.
[Candotti, Fabio] Univ Lausanne Hosp, Div Immunol & Allergy, CH-1011 Lausanne, Switzerland.
[Picard, Capucine; Bustamante, Jacinta; Casanova, Jean Laurent] Rockefeller Univ, Rockefeller Branch, St Giles Lab Human Genet Infect Dis, New York, NY 10065 USA.
[Picard, Capucine; Bustamante, Jacinta; Casanova, Jean Laurent] Howard Hughes Med Inst, New York, NY 10065 USA.
[Picard, Capucine; Bustamante, Jacinta; Casanova, Jean Laurent] Necker Hosp Sick Children, Lab Human Genet Infect Dis, INSERM, Necker Branch,U980, F-75015 Paris, France.
[Picard, Capucine; Bustamante, Jacinta; Casanova, Jean Laurent] Paris Descartes Univ, Imagine Inst, F-75015 Paris, France.
[Germeshausen, Manuela] Hannover Med Sch, Dept Pediat Hematol & Oncol, Hannover, Germany.
[Hershfield, Michael] Duke Univ, Med Ctr, Dept Biochem, Durham, NC 27706 USA.
[Maria Eraso, Ruth] Hosp Pablo Tobon Uribe, Serv Reumatol Pediat, Medellin, Colombia.
[Natalia Builes, Luz] Hosp Pablo Tobon Uribe, Dept Pediat, Medellin, Colombia.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0271-9142
EI 1573-2592
J9 J CLIN IMMUNOL
JI J. Clin. Immunol.
PD NOV
PY 2015
VL 35
SU 1
MA PL052
BP S23
EP S23
PG 1
WC Immunology
SC Immunology
GA CV0XR
UT WOS:000363977700049
ER
PT J
AU Cabanillas, D
Ninomiya, M
Garcia, M
Sosa, F
Blanco, J
Perez, L
Marciano, BE
Rosenzweig, S
Regairaz, L
AF Cabanillas, Diana
Ninomiya, Mariel
Garcia, Mariel
Sosa, Fernanda
Blanco, Jorgelina
Perez, Laura
Marciano, Beatriz E.
Rosenzweig, Sergio
Regairaz, Lorena
TI Granulocytes Transfusions as Salvage Therapy in 2 Patients with
Congenital Defects of Phagocyte and Invasive Fungal Infection
SO JOURNAL OF CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT 4th Meeting of the Latin-American-Society-for-Immunodeficiencies (LASID)
CY NOV 18-21, 2015
CL Buenos Aires, ARGENTINA
SP Latin Amer Soc Immunodeficiencies
C1 [Cabanillas, Diana; Regairaz, Lorena] Hosp Ninos Sor Maria Ludovica, Unidad Inmunol, La Plata, Buenos Aires, Argentina.
[Ninomiya, Mariel] Hosp Ninos Sor Maria Ludovica, Serv Hemoterapia, La Plata, Buenos Aires, Argentina.
[Garcia, Mariel; Sosa, Fernanda] Hosp Ninos Sor Maria Ludovica, Serv Infectol, La Plata, Buenos Aires, Argentina.
[Blanco, Jorgelina] Hosp Ninos Sor Maria Ludovica, Serv Neumonol, La Plata, Buenos Aires, Argentina.
[Perez, Laura] Hosp Pediat Juan P Garrahan, Lab Inmunol Humoral, Buenos Aires, DF, Argentina.
[Marciano, Beatriz E.] NIAID, Lab Clin Infect Dis, NIH, College Pk, MD USA.
[Rosenzweig, Sergio] NIH, Serv Immunol, Ctr Clin, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0271-9142
EI 1573-2592
J9 J CLIN IMMUNOL
JI J. Clin. Immunol.
PD NOV
PY 2015
VL 35
SU 1
MA PL122
BP S54
EP S55
PG 2
WC Immunology
SC Immunology
GA CV0XR
UT WOS:000363977700116
ER
PT J
AU Nievas, E
Rosenzweig, S
Bernasconi, A
Mannino, L
Dominguez, N
Ranea, G
Fernandez, MM
Stoddard, J
Niemela, J
AF Nievas, Elma
Rosenzweig, Sergio
Bernasconi, Andrea
Mannino, Leonardo
Dominguez, Nancy
Ranea, Gabriela
Marta Fernandez, Maria
Stoddard, Jennifer
Niemela, Julie
TI Recurrent and Severe Herpes Simplex Virus (HSV) Infection as the Only
Manifestation in a Patient with Tyk2 Deficiency (Tyk2D)
SO JOURNAL OF CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT 4th Meeting of the Latin-American-Society-for-Immunodeficiencies (LASID)
CY NOV 18-21, 2015
CL Buenos Aires, ARGENTINA
SP Latin Amer Soc Immunodeficiencies
C1 [Nievas, Elma] Pediat Hosp A Fleming OSEP, Immunoligy Unit, Mendoza, Argentina.
[Rosenzweig, Sergio] NIAID, Primary Immunodeficiency Clin, NIH, Bethesda, MD 20892 USA.
[Bernasconi, Andrea] Garrahan Hosp, Immunol & Reumatol Serv, Buenos Aires, DF, Argentina.
[Mannino, Leonardo] Pediat Hosp A Fleming OSEP, Infectol Unit, Mendoza, Argentina.
[Dominguez, Nancy; Ranea, Gabriela; Marta Fernandez, Maria] Pediat Hosp A Fleming OSEP, Pediat Unit, Mendoza, Argentina.
[Stoddard, Jennifer; Niemela, Julie] NIH, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0271-9142
EI 1573-2592
J9 J CLIN IMMUNOL
JI J. Clin. Immunol.
PD NOV
PY 2015
VL 35
SU 1
MA PL037
BP S15
EP S16
PG 2
WC Immunology
SC Immunology
GA CV0XR
UT WOS:000363977700034
ER
PT J
AU Vargas-Hernandez, A
Mace, EM
Freemabn, AF
Rosenzweig, S
Chinn, IK
Holland, SM
Orange, JS
Forbes, LR
AF Vargas-Hernandez, Alexander
Mace, Emily M.
Freemabn, Alexandra F.
Rosenzweig, Sergio
Chinn, Ivan K.
Holland, Steve M.
Orange, Jordan S.
Forbes, Lisa R.
TI Immature NK Cells with Impaired IL-15 Response in Patients with
STAT1-GOF Mutations
SO JOURNAL OF CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT 4th Meeting of the Latin-American-Society-for-Immunodeficiencies (LASID)
CY NOV 18-21, 2015
CL Buenos Aires, ARGENTINA
SP Latin Amer Soc Immunodeficiencies
C1 [Vargas-Hernandez, Alexander; Mace, Emily M.; Chinn, Ivan K.; Orange, Jordan S.; Forbes, Lisa R.] Baylor Coll Med, Houston, TX 77030 USA.
[Vargas-Hernandez, Alexander; Mace, Emily M.; Chinn, Ivan K.; Orange, Jordan S.; Forbes, Lisa R.] Texas Childrens Hosp, Ctr Human Immunobiol, Dept Allergy Immunol & Rheumatol, Houston, TX 77030 USA.
[Freemabn, Alexandra F.] NIAID, NIH, Bethesda, MD 20892 USA.
[Rosenzweig, Sergio; Holland, Steve M.] NIH, Clin Ctr, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0271-9142
EI 1573-2592
J9 J CLIN IMMUNOL
JI J. Clin. Immunol.
PD NOV
PY 2015
VL 35
SU 1
MA PL038
BP S16
EP S16
PG 1
WC Immunology
SC Immunology
GA CV0XR
UT WOS:000363977700035
ER
PT J
AU Villa, M
Rossi, J
Bernasconi, A
Rosenzweig, S
Stoddard, J
Niemela, J
Galeano, A
Daniela, F
Merhar, C
Lampugnani, A
Oleastro, M
AF Villa, Mariana
Rossi, Jorge
Bernasconi, Andrea
Rosenzweig, Sergio
Stoddard, Jennifer
Niemela, Julie
Galeano, Adriana
Daniela, Fortunati
Merhar, Claudia
Lampugnani, Alejandra
Oleastro, Matias
TI Central Nervous System (CNS) HHV-6 Infection in an Unusual Severe
Combined Immunodeficiency (SCID): ZAP 70 Deficiency
SO JOURNAL OF CLINICAL IMMUNOLOGY
LA English
DT Meeting Abstract
CT 4th Meeting of the Latin-American-Society-for-Immunodeficiencies (LASID)
CY NOV 18-21, 2015
CL Buenos Aires, ARGENTINA
SP Latin Amer Soc Immunodeficiencies
C1 [Villa, Mariana; Rossi, Jorge; Bernasconi, Andrea; Daniela, Fortunati; Merhar, Claudia; Oleastro, Matias] Hosp Pediat Prof Dr Juan P Garrahan, Immunol & Rheumatol Unit, Bethesda, MD USA.
[Rosenzweig, Sergio] NIH Clin Ctr, Serv Immunol, Bethesda, MD USA.
[Stoddard, Jennifer; Niemela, Julie] NIH Clin Ctr, DNA Sequencing Lab, Dept Lab Med, Bethesda, MD USA.
[Galeano, Adriana] FUNDALEU, Buenos Aires, DF, Argentina.
[Lampugnani, Alejandra] Hosp Rawson, San Juan, Provincia De Sa, Argentina.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0271-9142
EI 1573-2592
J9 J CLIN IMMUNOL
JI J. Clin. Immunol.
PD NOV
PY 2015
VL 35
SU 1
MA PL099
BP S44
EP S45
PG 2
WC Immunology
SC Immunology
GA CV0XR
UT WOS:000363977700095
ER
PT J
AU Walter, JE
Rosen, LB
Csomos, K
Rosenberg, JM
Mathew, D
Keszei, M
Ujhazi, B
Chen, K
Lee, YN
Tirosh, I
Dobbs, K
Al-Herz, W
Cowan, MJ
Puck, J
Bleesing, JJ
Grimley, MS
Malech, H
De Ravin, SS
Gennery, AR
Abraham, RS
Joshi, AY
Boyce, TG
Butte, MJ
Nadeau, KC
Balboni, I
Sullivan, KE
Akhter, J
Adeli, M
El-Feky, RA
El-Ghoneimy, DH
Dbaibo, G
Wakim, R
Azzari, C
Palma, P
Cancrini, C
Capuder, K
Condino-Neto, A
Costa-Carvalho, BT
Oliveira, JB
Roifman, C
Buchbinder, D
Kumanovics, A
Franco, JL
Niehues, T
Schuetz, C
Kuijpers, T
Yee, C
Chou, J
Masaad, MJ
Geha, R
Uze, G
Gelman, R
Holland, SM
Recher, M
Utz, PJ
Browne, SK
Notarangelo, LD
AF Walter, Jolan E.
Rosen, Lindsey B.
Csomos, Krisztian
Rosenberg, Jacob M.
Mathew, Divij
Keszei, Marton
Ujhazi, Boglarka
Chen, Karin
Lee, Yu Nee
Tirosh, Irit
Dobbs, Kerry
Al-Herz, Waleed
Cowan, Morton J.
Puck, Jennifer
Bleesing, Jack J.
Grimley, Michael S.
Malech, Harry
De Ravin, Suk See
Gennery, Andrew R.
Abraham, Roshini S.
Joshi, Avni Y.
Boyce, Thomas G.
Butte, Manish J.
Nadeau, Kari C.
Balboni, Imelda
Sullivan, Kathleen E.
Akhter, Javeed
Adeli, Mehdi
El-Feky, Reem A.
El-Ghoneimy, Dalia H.
Dbaibo, Ghassan
Wakim, Rima
Azzari, Chiara
Palma, Paolo
Cancrini, Caterina
Capuder, Kelly
Condino-Neto, Antonio
Costa-Carvalho, Beatriz T.
Oliveira, Joao Bosco
Roifman, Chaim
Buchbinder, David
Kumanovics, Attila
Luis Franco, Jose
Niehues, Tim
Schuetz, Catharina
Kuijpers, Taco
Yee, Christina
Chou, Janet
Masaad, Michel J.
Geha, Raif
Uze, Gulbu
Gelman, Rebecca
Holland, Steven M.
Recher, Mike
Utz, Paul J.
Browne, Sarah K.
Notarangelo, Luigi D.
TI Broad-spectrum antibodies against self-antigens and cytokines in RAG
deficiency
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Article
ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; SEVERE COMBINED IMMUNODEFICIENCY; CHRONIC
MUCOCUTANEOUS CANDIDIASIS; IMMUNOGLOBULIN-SECRETING CELLS; ACTIVATING
GENE-1 DEFICIENCY; MYASTHENIA-GRAVIS PATIENTS; SYNDROME TYPE-I;
OMENN-SYNDROME; AUTOIMMUNE-DISEASE; GRANULOMATOUS-DISEASE
AB Patients with mutations of the recombination-activating genes (RAG) present with diverse clinical phenotypes, including severe combined immune deficiency (SCID), autoimmunity, and inflammation. However, the incidence and extent of immune dysregulation in RAG-dependent immunodeficiency have not been studied in detail. Here, we have demonstrated that patients with hypomorphic RAG mutations, especially those with delayed-onset combined immune deficiency and granulomatous/ autoimmune manifestations (CID-G/AI), produce a broad spectrum of autoantibodies. Neutralizing anti-IFN-alpha or anti-IFN-omega antibodies were present at detectable levels in patients with CID-G/AI who had a history of severe viral infections. As this autoantibody profile is not observed in a wide range of other primary immunodeficiencies, we hypothesized that recurrent or chronic viral infections may precipitate or aggravate immune dysregulation in RAG-deficient hosts. We repeatedly challenged Rag1(5723C/5723C) mice, Le which serve as a model of leaky SCID, with agonists of the virus-recognizing receptors TLR3/MDA5, TLR7/-8, and TLR9 and found that this treatment elicits autoantibody production. Altogether, our data demonstrate that immune dysregulation is an integral aspect of RAG-associated immunodeficiency and indicate that environmental triggers may modulate the phenotypic expression of autoimmune manifestations.
C1 [Walter, Jolan E.; Csomos, Krisztian; Ujhazi, Boglarka] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Allergy & Immunol, Boston, MA USA.
[Walter, Jolan E.; Csomos, Krisztian; Ujhazi, Boglarka] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Immunol & Inflammatory Dis, Boston, MA USA.
[Walter, Jolan E.; Lee, Yu Nee; Dobbs, Kerry; Capuder, Kelly; Yee, Christina; Chou, Janet; Masaad, Michel J.; Geha, Raif; Notarangelo, Luigi D.] Boston Childrens Hosp, Div Immunol, Boston, MA 02115 USA.
[Rosen, Lindsey B.; Uze, Gulbu; Holland, Steven M.; Browne, Sarah K.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
[Rosenberg, Jacob M.; Utz, Paul J.] Stanford Univ, Dept Med, Div Rheumatol & Immunol, Stanford, CA 94305 USA.
[Mathew, Divij] Univ Colorado, Integrated Dept Immunol, Natl Jewish Hlth, Denver, CO 80202 USA.
[Keszei, Marton] Karolinska Inst, Dept Microbiol Tumor & Cell Biol, Stockholm, Sweden.
[Ujhazi, Boglarka] Univ Debrecen, Dept Biochem & Mol Biol, Debrecen, Hungary.
[Chen, Karin] Univ Utah, Div Allergy Immunol & Rheumatol, Dept Pediat, Salt Lake City, UT USA.
[Tirosh, Irit] Boston Childrens Hosp, Pediat Rheumatol, Boston, MA 02115 USA.
[Al-Herz, Waleed] Kuwait Univ, Dept Pediat, Fac Med, Kuwait, Kuwait.
[Cowan, Morton J.; Puck, Jennifer] UCSF Benioff Childrens Hosp, Pediat Allergy Immunol & Blood & MarrowTransplant, San Francisco, CA USA.
[Bleesing, Jack J.; Grimley, Michael S.] Cincinnati Childrens Hosp Med Ctr, Div Bone Marrow Transplantat & Immunodeficiency, Cincinnati, OH 45229 USA.
[Malech, Harry; De Ravin, Suk See] NIAID, Lab Host Defenses, NIH, Bethesda, MD 20892 USA.
[Gennery, Andrew R.] Newcastle Upon Tyne Hosp, Dept Pediat Immunol, Newcastle Upon Tyne, Tyne & Wear, England.
[Gennery, Andrew R.] Newcastle Upon Tyne Hosp, Inst Cellular Med, Newcastle Upon Tyne, Tyne & Wear, England.
[Abraham, Roshini S.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA.
[Joshi, Avni Y.] Mayo Clin, Div Pediat Allergy Immunol, Dept Pediat & Adolescent Med, Rochester, MN USA.
[Boyce, Thomas G.] Mayo Clin, Div Pediat Infect Dis, Dept Pediat, Rochester, MN USA.
[Butte, Manish J.; Nadeau, Kari C.; Balboni, Imelda] Stanford Univ, Dept Pediat, Div Allergy, Immunol,Rheumatol, Stanford, CA 94305 USA.
[Sullivan, Kathleen E.] Childrens Hosp Philadelphia, Allergy & Immunol, Philadelphia, PA 19104 USA.
[Akhter, Javeed] Advocate Childrens Hosp, Jeffrey Modell Fdn Immunol Referral Ctr, Oak Lawn, IL USA.
[Adeli, Mehdi] Hamad Med Corp, Dept Pediat, Weill Cornell Med Coll, Doha, Qatar.
[El-Feky, Reem A.; El-Ghoneimy, Dalia H.] Ain Shams Univ, Dept Pediat Allergy & Immunol, Childrens Hosp, Fac Med, Cairo, Egypt.
[Dbaibo, Ghassan; Wakim, Rima] Amer Univ Beirut, Dept Pediat & Adolescent Med, Beirut, Lebanon.
[Azzari, Chiara] Anna Meyer Childrens Univ Hosp, Florence, Italy.
[Palma, Paolo; Cancrini, Caterina] IRCCS Bambino Gasu Childrens Hosp, Univ Dept Paediat, Rome, Italy.
[Condino-Neto, Antonio] Univ Sao Paulo, Dept Immunol, Inst Biomed Sci, Sao Paulo, Brazil.
[Costa-Carvalho, Beatriz T.] Univ Fed Sao Paulo, Sao Paulo, Brazil.
[Oliveira, Joao Bosco] Inst Med Integral, Recife, PE, Brazil.
[Roifman, Chaim] Univ Toronto, Hosp Sick Children, Toronto, ON M5G 1X8, Canada.
[Buchbinder, David] UC Irvine, Pediat Hematol, CHOC Childrens Hosp, Orange, CA USA.
[Kumanovics, Attila] Univ Utah, Dept Pathol, Salt Lake City, UT USA.
[Luis Franco, Jose] Univ Antioquia, Grp Primary Immunodeficiencies, Dept Microbiol & Parasitol, Sch Med, Medellin, Colombia.
[Niehues, Tim] Univ Dusseldorf, Ctr Child Hlth & Adolescence, Helios Klinikum Krefeld Acad Hosp, Dusseldorf, Germany.
[Schuetz, Catharina] Univ Hosp Ulm, Dept Pediat & Adolescent Med, Ulm, Germany.
[Kuijpers, Taco] Univ Amsterdam, Acad Med Ctr, Emma Childrens Hosp, NL-1105 AZ Amsterdam, Netherlands.
[Gelman, Rebecca] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA.
[Recher, Mike] Univ Basel Hosp, Immunodeficiency Clin, Med Outpatient Unit, CH-4031 Basel, Switzerland.
[Recher, Mike] Univ Basel Hosp, Immunodeficiency Lab, Dept Biomed, CH-4031 Basel, Switzerland.
[Utz, Paul J.] Stanford Univ, Inst Immun Transplantat & Infect, Stanford, CA 94305 USA.
[Notarangelo, Luigi D.] Harvard Univ, Harvard Stem Cell Inst, Boston, MA 02115 USA.
RP Notarangelo, LD (reprint author), Boston Childrens Hosp, Div Immunol, Karp Res Bldg,Room 10217,One Blackfan Circle, Boston, MA 02115 USA.
EM jewalter@mgh.harvard.edu; Luigi.Notarangelo@childrens.harvard.edu
RI Notarangelo, Luigi/F-9718-2016; Keszei, Marton/F-3295-2014;
OI Notarangelo, Luigi/0000-0002-8335-0262; Keszei,
Marton/0000-0002-1158-2179; Adeli, Mehdi/0000-0002-3051-3080; Malech,
Harry/0000-0001-5874-5775; Palma, Paolo/0000-0002-3066-4719; cancrini,
caterina/0000-0001-8410-9617; Butte, Manish/0000-0002-4490-5595
FU NIAID, NIH [5R01AI100887, U54AI082973, 5K08AI103035, T32GM007365];
Manton Foundation; Jeffrey Modell Foundation; Intramural Research
Program of the NIAID, NIH
FX This work was partly supported by grants from the NIAID, NIH
(5R01AI100887 and U54AI082973, to L.D. Notarangelo; 5K08AI103035, to
J.E. Walter; and T32GM007365, to P.J. Utz); the Manton Foundation (to
L.D. Notarangelo); and the Jeffrey Modell Foundation (to L.D.
Notarangelo). This research was also supported in part by the Intramural
Research Program of the NIAID, NIH (to L.B. Rosen, S.M. Holland, and
S.K. Browne). We acknowledge Quan-Zhen Li and Jinchun Zhou of the
Genomics and Microarray Core Facility at the University of Texas
Southwestern Medical Center for autoantibody profiling using autoantigen
microarrays.
NR 68
TC 16
Z9 16
U1 3
U2 6
PU AMER SOC CLINICAL INVESTIGATION INC
PI ANN ARBOR
PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA
SN 0021-9738
EI 1558-8238
J9 J CLIN INVEST
JI J. Clin. Invest.
PD NOV
PY 2015
VL 125
IS 11
BP 4135
EP 4148
DI 10.1172/JCI80477
PG 14
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA CV2TL
UT WOS:000364110000017
PM 26457731
ER
PT J
AU Gao, QQ
Wyatt, E
Goldstein, JA
LoPresti, P
Castillo, LM
Gazda, A
Petrossian, N
Earley, JU
Hadhazy, M
Barefield, DY
Demonbreun, AR
Bonnemann, C
Wolf, M
McNally, EM
AF Gao, Quan Q.
Wyatt, Eugene
Goldstein, Jeff A.
LoPresti, Peter
Castillo, Lisa M.
Gazda, Alec
Petrossian, Natalie
Earley, Judy U.
Hadhazy, Michele
Barefield, David Y.
Demonbreun, Alexis R.
Boennemann, Carsten
Wolf, Matthew
McNally, Elizabeth M.
TI Reengineering a transmembrane protein to treat muscular dystrophy using
exon skipping
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Article
ID MURINE SKELETAL-MUSCLE; SARCOGLYCAN COMPLEX; GAMMA-SARCOGLYCAN;
GLYCOPROTEIN COMPLEX; BETA-SARCOGLYCAN; DELTA-SARCOGLYCAN;
GENE-EXPRESSION; DROSOPHILA; MUTATIONS; HEART
AB Exon skipping uses antisense oligonucleotides as a treatment for genetic diseases. The antisense oligonucleotides used for exon skipping are designed to bypass premature stop codons in the target RNA and restore reading frame disruption. Exon skipping is currently being tested in humans with dystrophin gene mutations who have Duchenne muscular dystrophy. For Duchenne muscular dystrophy, the rationale for exon skipping derived from observations in patients with naturally occurring dystrophin gene mutations that generated internally deleted but partially functional dystrophin proteins. We have now expanded the potential for exon skipping by testing whether an internal, in-frame truncation of a transmembrane protein gamma-sarcoglycan is functional. We generated an internally truncated gamma-sarcoglycan protein that we have termed Mini-Gamma by deleting a large portion of the extracellular domain. Mini-Gamma provided functional and pathological benefits to correct the loss of gamma-sarcoglycan in a Drosophila model, in heterologous cell expression studies, and in transgenic mice lacking gamma-sarcoglycan. We generated a cellular model of human muscle disease and showed that multiple exon skipping could be induced in RNA that encodes a mutant human gamma-sarcoglycan. Since Mini-Gamma represents removal of 4 of the 7 coding exons in gamma-sarcoglycan, this approach provides a viable strategy to treat the majority of patients with gamma-sarcoglycan gene mutations.
C1 [Gao, Quan Q.] Univ Chicago, Comm Dev Regenerat & Stem Cell Biol, Chicago, IL 60637 USA.
[Wyatt, Eugene; Castillo, Lisa M.; Earley, Judy U.; Hadhazy, Michele; Barefield, David Y.; Demonbreun, Alexis R.; McNally, Elizabeth M.] Northwestern Univ, Ctr Genet Med, Evanston, IL USA.
[Goldstein, Jeff A.; LoPresti, Peter; Gazda, Alec; Petrossian, Natalie] Univ Chicago, Dept Pathol, Chicago, IL 60637 USA.
[Boennemann, Carsten] NINDS, NIH, Bethesda, MD 20892 USA.
[Wolf, Matthew] Duke Univ, Dept Med, Durham, NC USA.
RP McNally, EM (reprint author), Northwestern Univ, Ctr Genet Med, 303 E Super St, Chicago, IL 60302 USA.
EM elizabeth.mcnally@northwestern.edu
FU NIH [R01HL61322, U54AR052646, R01HL116581]
FX We thank the Kurt + Peter Foundation for facilitating these studies, and
the patient and families for participation. We thank Jeff Chamberlain
for providing the inducible MyoD construct. This work was supported by
NIH R01HL61322 and U54AR052646 (to E.M. McNally), and NIH R01HL116581
(to M.J. Wolf).
NR 57
TC 4
Z9 4
U1 0
U2 3
PU AMER SOC CLINICAL INVESTIGATION INC
PI ANN ARBOR
PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA
SN 0021-9738
EI 1558-8238
J9 J CLIN INVEST
JI J. Clin. Invest.
PD NOV
PY 2015
VL 125
IS 11
BP 4186
EP 4195
DI 10.1172/JCI82768
PG 10
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA CV2TL
UT WOS:000364110000021
PM 26457733
ER
PT J
AU Brehm, A
Liu, Y
Sheikh, A
Marrero, B
Omoyinmi, E
Zhou, Q
Montealegre, G
Biancotto, A
Reinhardt, A
de Jesus, AA
Pelletier, M
Tsai, WXL
Remmers, EF
Kardava, L
Hill, S
Kim, H
Lachmann, HJ
Megarbane, A
Chae, JJ
Brady, J
Castillo, RD
Brown, D
Casano, AV
Gao, L
Chapelle, D
Huang, Y
Stone, D
Chen, YQ
Sotzny, F
Lee, CCR
Kastner, DL
Torrelo, A
Zlotogorski, A
Moir, S
Gadina, M
McCoy, P
Wesley, R
Rother, K
Hildebrand, PW
Brogan, P
Kruger, E
Aksentijevich, I
Goldbach-Mansky, R
AF Brehm, Anja
Liu, Yin
Sheikh, Afzal
Marrero, Bernadette
Omoyinmi, Ebun
Zhou, Qing
Montealegre, Gina
Biancotto, Angelique
Reinhardt, Adam
de Jesus, Adriana Almeida
Pelletier, Martin
Tsai, Wanxia L.
Remmers, Elaine F.
Kardava, Lela
Hill, Suvimol
Kim, Hanna
Lachmann, Helen J.
Megarbane, Andre
Chae, Jae Jin
Brady, Jilian
Castillo, Rhina D.
Brown, Diane
Vera Casano, Angel
Gao, Ling
Chapelle, Dawn
Huang, Yan
Stone, Deborah
Chen, Yongqing
Sotzny, Franziska
Lee, Chyi-Chia Richard
Kastner, Daniel L.
Torrelo, Antonio
Zlotogorski, Abraham
Moir, Susan
Gadina, Massimo
McCoy, Phil
Wesley, Robert
Rother, Kristina
Hildebrand, Peter W.
Brogan, Paul
Krueger, Elke
Aksentijevich, Ivona
Goldbach-Mansky, Raphaela
TI Additive loss-of-function proteasome subunit mutations in CANDLE/PRAAS
patients promote type I IFN production
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Article
ID AUTOINFLAMMATORY DISEASES; DIGENIC INHERITANCE; IMMUNE-RESPONSES; 20S
PROTEASOME; LINKED LMP; GENE; IMMUNOPROTEASOMES; LIPODYSTROPHY; MHC;
EXPRESSION
AB Autosomal recessive mutations in proteasome subunit beta 8 (PSMB8), which encodes the inducible proteasome subunit beta Si, cause the immune-dysregulatory disease chronic atypical neutrophilic dermatosis with lipodystrophy and elevated temperature (CANDLE), which is classified as a proteasome-associated autoinflammatory syndrome (PRAAS). Here, we identified 8 mutations in 4 proteasome genes, PSMA3 (encodes alpha 7), PSMB4 (encodes beta 7) PSMB9 (encodes beta 1i), and proteasome maturation protein (POMP), that have not been previously associated with disease and 1 mutation in PSMB8 that has not been previously reported. One patient was compound heterozygous for PSMB4 mutations, 6 patients from 4 families were heterozygous for a missense mutation in 1 inducible proteasome subunit and a mutation in a constitutive proteasome subunit, and 1 patient was heterozygous for a POMP mutation, thus establishing a digenic and autosomal dominant inheritance pattern of PRAAS. Function evaluation revealed that these mutations variably affect transcription, protein expression, protein folding, proteasome assembly, and, ultimately, proteasome activity. Moreover, defects in proteasome formation and function were recapitulated by siRNA-mediated knockdown of the respective subunits in primary fibroblasts from healthy individuals. Patient-isolated hematopoietic and nonhematopoietic cells exhibited a strong IFN gene-expression signature, irrespective of genotype. Additionally, chemical proteasome inhibition or progressive depletion of proteasome subunit gene transcription with siRNA induced transcription of type I IFN genes in healthy control cells. Our results provide further insight into CANDLE genetics and link global proteasome dysfunction to increased type I IFN production.
C1 [Brehm, Anja; Sotzny, Franziska; Krueger, Elke] Charite, Inst Biochem, D-13353 Berlin, Germany.
[Liu, Yin; Sheikh, Afzal; Marrero, Bernadette; Montealegre, Gina; de Jesus, Adriana Almeida; Kim, Hanna; Chapelle, Dawn; Huang, Yan; Chen, Yongqing; Goldbach-Mansky, Raphaela] NIAMS, Translat Autoinflammatory Dis Sect, NIH, Bethesda, MD 20892 USA.
[Sheikh, Afzal; Zhou, Qing; Remmers, Elaine F.; Chae, Jae Jin; Brady, Jilian; Stone, Deborah; Kastner, Daniel L.; Aksentijevich, Ivona] NHGRI, Inflammatory Dis Sect, NIH, Bethesda, MD 20892 USA.
[Omoyinmi, Ebun; Brogan, Paul] UCL, Inst Child Hlth, London, England.
[Omoyinmi, Ebun; Brogan, Paul] NHS Fdn Trust, Great Ormond St Hosp, London, England.
[Biancotto, Angelique; McCoy, Phil] NHLBI, Ctr Human Immunol, NIH, Bethesda, MD 20892 USA.
[Reinhardt, Adam] Childrens Hosp & Med Ctr, Omaha, NE USA.
[Reinhardt, Adam] Univ Nebraska Med Ctr, Omaha, NE USA.
[Pelletier, Martin] NIAMS, Autoimmun Branch, Bethesda, MD USA.
[Tsai, Wanxia L.; Gadina, Massimo] NIAMS, Off Sci & Technol, Bethesda, MD USA.
[Kardava, Lela; Moir, Susan] NIAID, Immunoregulat Lab, Bethesda, MD 20892 USA.
[Hill, Suvimol] NIH, Ctr Clin, Bethesda, MD 20892 USA.
[Lachmann, Helen J.] UCL, Sch Med, Natl Amyloidosis Ctr, London W1N 8AA, England.
[Megarbane, Andre] St Joseph Univ, Med Genet Unit, Beirut, Lebanon.
[Megarbane, Andre] Inst Jerome Lejeune, Paris, France.
[Castillo, Rhina D.; Brown, Diane] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA.
[Castillo, Rhina D.; Brown, Diane] Univ So Calif, Los Angeles, CA USA.
[Vera Casano, Angel] Hosp Carlos Haya, Malaga, Andalusia, Spain.
[Gao, Ling] Univ Arkansas Med Sci, Coll Med, Little Rock, AR 72205 USA.
[Lee, Chyi-Chia Richard] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA.
[Torrelo, Antonio] Hosp Nino Jesus, Pediat Dermatol, Madrid, Spain.
[Zlotogorski, Abraham] Hadassah Hebrew Univ, Med Ctr, Jerusalem, Israel.
[Wesley, Robert] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Reprod Biol & Med Branch, Bethesda, MD USA.
[Rother, Kristina] NIDDK, Sect Pediat Diabet & Metab, NIH, Bethesda, MD 20892 USA.
[Hildebrand, Peter W.] Charite, Inst Med Phys & Biophys, D-10117 Berlin, Germany.
RP Goldbach-Mansky, R (reprint author), NIAMS, Translat Autoinflammatory Dis Sect, NIH, Bldg 10,Room 6D47B,10 Ctr Dr, Bethesda, MD 20892 USA.
EM elke.krueger@charite.de; goldbacr@mail.nih.gov
RI Yu, Xiaomin/I-6407-2016; Kruger, Elke/B-1462-2012;
OI Kruger, Elke/0000-0002-2551-242X; Kim, Hanna/0000-0002-0595-6533
FU Intramural Research Program of NIAMS at the NIH; Berlin Institute of
Health; Deutsche Forschungsgemeinschaft [SFB TR 43, SFB740]
FX The authors would like to thank the following colleagues for their help:
Christina Zaal and Evelyn Ralston for microscopy images, Hong-Wei Sun
and Stephen Brooks for gene-expression analysis, Nigel Klein for
proteolytic functional work on patients 4 and 5, Clarissa Pilkington for
clinical recruitment of patients 6 and 7, Mirna Hashem Medly, Elon Pras
for the Palestinian control samples, Nicole Plass and Michelle O'Brien
for patient care, and Daniela Ludwig for technical help on siRNA
experiments. This research was supported by the Intramural Research
Program of NIAMS at the NIH, by the Berlin Institute of Health, and by
the Deutsche Forschungsgemeinschaft (SFB TR 43 to E. Kruger, SFB740 to
E. Kruger and P.W. Hildebrand).
NR 46
TC 22
Z9 25
U1 3
U2 9
PU AMER SOC CLINICAL INVESTIGATION INC
PI ANN ARBOR
PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA
SN 0021-9738
EI 1558-8238
J9 J CLIN INVEST
JI J. Clin. Invest.
PD NOV
PY 2015
VL 125
IS 11
BP 4196
EP 4211
DI 10.1172/JCI81260
PG 16
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA CV2TL
UT WOS:000364110000022
PM 26524591
ER
PT J
AU Grady, PA
Gough, LL
AF Grady, Patricia A.
Gough, Lisa Lucio
TI Nursing Science: Claiming the Future
SO JOURNAL OF NURSING SCHOLARSHIP
LA English
DT Article
DE History/trends; other
ID SELF-MANAGEMENT INTERVENTION; IRRITABLE-BOWEL-SYNDROME; NATIONAL
INSTITUTE; AFRICAN-AMERICAN; EMERGING AREAS; LATINO PARENTS; IDEA
FESTIVAL; PROGRAM; PREVENTION; EDUCATION
AB PurposeThe National Institute of Nursing Research (NINR) is dedicated to improving health and health care through the funding of nursing science and research training. With a focus on guiding the nation's nursing science research agenda and improving quality of life, the NINR is ideally positioned to meet current healthcare challenges and anticipate future challenges and priorities. In this article, coinciding with the NINR's 30th anniversary, examples of NINR-supported research are described, along with its training activities designed to develop a strong cadre of 21st century nurse scientists. In addition, we discuss priorities and future directions for advancing cutting-edge nursing science to claim the future and improve the health of the nation over the next 30 years and beyond.
C1 [Grady, Patricia A.; Gough, Lisa Lucio] NINR, NIH, Bethesda, MD 20817 USA.
RP Gough, LL (reprint author), NINR, Div Sci Policy & Publ Liaison, Sci Implementat Branch, 6701 Democracy Blvd,Suite 710, Bethesda, MD 20817 USA.
EM goughll@mail.nih.gov
NR 49
TC 3
Z9 3
U1 1
U2 9
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1527-6546
EI 1547-5069
J9 J NURS SCHOLARSHIP
JI J. Nurs. Scholarsh.
PD NOV
PY 2015
VL 47
IS 6
BP 512
EP 521
DI 10.1111/jnu.12170
PG 10
WC Nursing
SC Nursing
GA CV0NY
UT WOS:000363948700005
PM 26448502
ER
PT J
AU Mumford, SL
Kim, S
Chen, Z
Barr, DB
Louis, GMB
AF Mumford, Sunni L.
Kim, Sungduk
Chen, Zhen
Barr, Dana Boyd
Louis, Germaine M. Buck
TI Urinary Phytoestrogens Are Associated with Subtle Indicators of Semen
Quality among Male Partners of Couples Desiring Pregnancy
SO JOURNAL OF NUTRITION
LA English
DT Article
DE isoflavones; lignans; phytoestrogens; semen quality; male fertility
ID SERUM ENTEROLACTONE CONCENTRATION; CHROMATIN STRUCTURE ASSAY; SPERM DNA
INTEGRITY; REPRODUCTIVE HEALTH; LIPID CONCENTRATIONS; MALE-INFERTILITY;
MALE RATS; SOY FOOD; MEN; EXPOSURE
AB Background: Phytoestrogens have been associated with subtle hormonal changes, although effects on male fecundity are largely unknown.
Objective: We evaluated associations between male urinary phytoestrogen (isoflavone and lignan) concentrations and semen quality.
Methods: This study was a prospective cohort study of 501 male partners of couples desiring pregnancy and discontinuing contraception. Each participant provided up to 2 semen samples that were analyzed for 35 semen quality endpoints the following day. Linear mixed-effects models were used to estimate associations between baseline urinary phytoestrogen concentrations and semen,quality parameters, adjusted for age, body mass index (BM!), research site, and serum lipid and cotinine concentrations.
Results: Most associations between urinary phytoestrogens and semen quality parameters were null. However, select individual phytoestrogens were associated with semen quality parameters, with associations dependent on the class of phytoestrogens and modified by BMI. Specifically, genistein and daidzein were associated with a lower percentage of normal sperm and increased abnormalities in semen morphology, with reduced associations observed as BMI increased (P < 0.05) [percentages (95% CIs) of normal morphology by WHO traditional criteria: genistein, main effect: -5.61% (-9.42%, -1.79%); interaction: 0.19% (0.06%, 0.31%) per log unit increase; daidzein, main effect: -5.35% (-9.36%, -1.34%); interaction: 0.18% (0.05%, 0.32%) per log unit increase]. Enterolactone was associated with fewer abnormalities in semen morphometry and morphology and decreased DNA fragmentation, with reduced associations observed as BMI increased (P < 0.05) [percentages (95% CIs) of abnormalities in the neck and midpiece: enterolactone, main effect: -3.35% (-6.51%, -0.19%); interaction: 0.11% (0.01%, 0.21%) per log unit increase].
Conclusions: These results suggest that male urinary phytoestrogen concentrations characteristic of the US population may be associated with subtle indicators of male fecundity and semen quality but were not associated with couple fecundity.
C1 [Mumford, Sunni L.; Kim, Sungduk; Chen, Zhen; Louis, Germaine M. Buck] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Barr, Dana Boyd] Emory Univ, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA.
RP Mumford, SL (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
EM mumfords@mail.nih.gov
OI Buck Louis, Germaine/0000-0002-1774-4490
FU NIH, Eunice Kennedy Shriver National Institute of Child Health and Human
Development [N01-HD-3-3355, N01-HD-3-3356, N01-HD-3-3358]
FX Supported by the Intramural Research Program of the NIH, Eunice Kennedy
Shriver National Institute of Child Health and Human Development
(contracts N01-HD-3-3355, N01-HD-3-3356, and N01-HD-3-3358).
NR 65
TC 3
Z9 3
U1 4
U2 11
PU AMER SOC NUTRITION-ASN
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-3166
EI 1541-6100
J9 J NUTR
JI J. Nutr.
PD NOV
PY 2015
VL 145
IS 11
BP 2535
EP 2541
DI 10.3945/jn.115.214973
PG 7
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA CV4VP
UT WOS:000364264900014
PM 26423741
ER
PT J
AU Littmann, T
Gottle, M
Reinartz, MT
Kalble, S
Wainer, IW
Ozawa, T
Seifert, R
AF Littmann, Timo
Goettle, Martin
Reinartz, Michael T.
Kaelble, Solveig
Wainer, Irving W.
Ozawa, Takeaki
Seifert, Roland
TI Recruitment of beta-Arrestin 1 and 2 to the beta(2)-Adrenoceptor:
Analysis of 65 Ligands
SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
LA English
DT Article
ID PROTEIN-COUPLED RECEPTORS; AIRWAY SMOOTH-MUSCLE; 7-TRANSMEMBRANE
RECEPTORS; FENOTEROL STEREOISOMERS; RACEMIC ALBUTEROL; CELLS;
ADRENOCEPTOR; MICE; DESENSITIZATION; ACTIVATION
AB Beyond canonical signaling via G(alpha)s and cAMP, the concept of functional selectivity at beta(2)-adrenoceptors (beta(2)ARs) describes the ability of adrenergic drugs to stabilize ligand-specific receptor conformations to initiate further signaling cascades comprising additional G-protein classes or beta-arrestins (beta arr). A set of 65 adrenergic ligands including 40 agonists and 25 antagonists in either racemic or enantiopure forms was used for barr recruitment experiments based on a split-luciferase assay in a cellular system expressing beta(2)AR. Many agonists showed only (weak) partial agonism regarding barr recruitment. Potencies and/or efficacies increased depending on the number of chirality centers in (R) configuration; no (S)-configured distomer was more effective at inducing beta arr recruitment other than the eutomer. beta arr2 was recruited more effectively than beta arr1. The analysis of antagonists revealed no significant effects on barr recruitment. Several agonists showed preference for activation of G(alpha)s GTPase relative to beta arr recruitment, and no beta arr-biased ligand was identified. In conclusion: 1) agonists show strong bias for G(alpha)s activation relative to barr recruitment; 2) agonists recruit beta arr1 and beta arr2 with subtle differences; and 3) there is no evidence for beta arr recruitment by antagonists.
C1 [Littmann, Timo; Goettle, Martin; Reinartz, Michael T.; Kaelble, Solveig; Seifert, Roland] Hannover Med Sch, Inst Pharmacol, D-30625 Hannover, Germany.
[Wainer, Irving W.] NIA, Lab Clin Invest, Baltimore, MD 21224 USA.
[Ozawa, Takeaki] Univ Tokyo, Dept Chem, Sch Sci, Tokyo 113, Japan.
RP Seifert, R (reprint author), Hannover Med Sch, Inst Pharmacol, Carl Neuberg Str 1, D-30625 Hannover, Germany.
EM seifert.roland@mh-hannover.de
FU internal funds of the Hannover Medical School
FX This work was supported by internal funds of the Hannover Medical
School. The authors declare no conflict of interest.
NR 53
TC 0
Z9 0
U1 0
U2 8
PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA
SN 0022-3565
EI 1521-0103
J9 J PHARMACOL EXP THER
JI J. Pharmacol. Exp. Ther.
PD NOV
PY 2015
VL 355
IS 2
BP 183
EP +
DI 10.1124/jpet.115.227959
PG 30
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA CV3MT
UT WOS:000364164000007
PM 26306764
ER
PT J
AU Lee, JW
Chou, CL
Knepper, MA
AF Lee, Jae Wook
Chou, Chung-Lin
Knepper, Mark A.
TI Deep Sequencing in Microdissected Renal Tubules Identifies Nephron
Segment-Specific Transcriptomes
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Article
ID COLLECTING DUCT CELLS; RNA-SEQ; GENE-EXPRESSION; MESSENGER-RNA;
SINGLE-CELL; RAT-KIDNEY; NA,K-ATPASE; SUSPENSION; PROTEIN; VIEW
AB The function of each renal tubule segment depends on the genes expressed therein. High-throughput methods used for global profiling of gene expression in unique cell types have shown low sensitivity and high false positivity, thereby limiting the usefulness of these methods in transcriptomic research. However, deep sequencing of RNA species (RNA-seq) achieves highly sensitive and quantitative transcriptomic profiling by sequencing RNAs in a massive, parallel manner. Here, we used RNA-seq coupled with classic renal tubule microdissection to comprehensively profile gene expression in each of 14 renal tubule segments from the proximal tubule through the inner medullary collecting duct of rat kidneys. Polyadenylated mRNAs were captured by oligo-dT primers and processed into adapter-ligated cDNA libraries that were sequenced using an Illumina platform. Transcriptomes were identified to a median depth of 8261 genes in microdissected renal tubule samples (105 replicates in total) and glomeruli (5 replicates). Manual nnicrodissection allowed a high degree of sample purity, which was evidenced by the observed distributions of well established cell specific markers. The main product of this work is an extensive database of gene expression along the nephron provided as a publicly accessible webpage (https://helixweb.nih.gov/ESBUDatabase/NephronRNAseq/index.html). The data also provide genome-wide maps of alternative exon usage and polyadenylation sites in the kidney. We illustrate the use of the data by profiling transcription factor expression along the renal tubule and mapping metabolic pathways.
C1 [Lee, Jae Wook; Chou, Chung-Lin; Knepper, Mark A.] NHLBI, Epithelial Syst Biol Lab, Syst Biol Ctr, NIH, Bethesda, MD 20892 USA.
RP Knepper, MA (reprint author), NIH, Bldg 10,Room 6N307,10 Ctr Dr,MSC-1603, Bethesda, MD 20892 USA.
EM knep@helix.nih.gov
FU Division of Intramural Research, NHLBI [ZIA-HL001285, ZIA-HL006129]
FX The work was funded by Division of Intramural Research, NHLBI Projects
ZIA-HL001285 and ZIA-HL006129 (to M.A.K.).
NR 41
TC 44
Z9 44
U1 2
U2 7
PU AMER SOC NEPHROLOGY
PI WASHINGTON
PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA
SN 1046-6673
EI 1533-3450
J9 J AM SOC NEPHROL
JI J. Am. Soc. Nephrol.
PD NOV
PY 2015
VL 26
IS 11
BP 2669
EP 2677
DI 10.1681/ASN.2014111067
PG 9
WC Urology & Nephrology
SC Urology & Nephrology
GA CV0CR
UT WOS:000363915500012
PM 25817355
ER
PT J
AU Kasembeli, AN
Duarte, R
Ramsay, M
Mosiane, P
Dickens, C
Dix-Peek, T
Limou, S
Sezgin, E
Nelson, GW
Fogo, AB
Goetsch, S
Kopp, JB
Winkler, CA
Naicker, S
AF Kasembeli, Alex N.
Duarte, Raquel
Ramsay, Michele
Mosiane, Pulane
Dickens, Caroline
Dix-Peek, Therese
Limou, Sophie
Sezgin, Efe
Nelson, George W.
Fogo, Agnes B.
Goetsch, Stewart
Kopp, Jeffrey B.
Winkler, Cheryl A.
Naicker, Saraladevi
TI APOL1 Risk Variants Are Strongly Associated with HIV-Associated
Nephropathy in Black South Africans
SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Article
ID FOCAL SEGMENTAL GLOMERULOSCLEROSIS; GENOME-WIDE ASSOCIATION; CHRONIC
KIDNEY-DISEASE; STAGE RENAL-DISEASE; POPULATION; AMERICANS; PROGRESSION;
INITIATION; INFECTION; SPECTRUM
AB APOL1 variants are associated with HIV-associated nephropathy and FSGS in African Americans. The prevalence of these variants in African populations with CKD in HIV-1 infection has not been investigated. We determined the role of APOL1 variants in 120 patients with HIV-associated nephropathy and CKD and 108 controls from a SouthAfrican black population. Patients with CKD were selected on the basis of histology. Genotypes were successfully determined for APOL1 G1 and G2 variants and 42 single nucleotide polynnorphisms, including 18 ancestry informative markers, for 116 patients with CKD (96.7%; 38 patients with HIV-associated nephropathy, 39 patients with HIV-positive CKD, and 39 patients with HIV-negative CKD), and 108 controls (100%). Overall, 79% of patients with HIV-associated nephropathy and 2% of population controls carried two risk alleles. In a recessive model, individuals carrying any combination of two APOL1 risk alleles had 89-fold higher odds (95% confidence interval, 18 to 912; P<0.001) of developing HIV-associated nephropathy compared with HIV-positive controls. Population allele frequencies were 7.3% for G1 and 11.1% for G2. APOL1 risk alleles were not significantly associated with other forms of CKD. These results indicate HIV-positive, antiretroviral therapy-naive South-African blacks with two APOL1 risk alleles are at very high risk for developing HIV-associated nephropathy. Further studies are required to determine the effect of APOL1 risk variants on kidney diseases in other regions of sub-Saharan Africa.
C1 [Kasembeli, Alex N.; Duarte, Raquel; Dickens, Caroline; Dix-Peek, Therese; Naicker, Saraladevi] Univ Witwatersrand, Fac Hlth Sci, Dept Internal Med, ZA-2193 Johannesburg, South Africa.
[Ramsay, Michele] Univ Witwatersrand, Sydney Brenner Inst Mol Biosci, Fac Hlth Sci, Div Human Genet,Natl Hlth Lab Serv,Sch Pathol, ZA-2193 Johannesburg, South Africa.
[Mosiane, Pulane] Univ Witwatersrand, Natl Hlth Lab Serv, Dept Anat Pathol, ZA-2193 Johannesburg, South Africa.
[Limou, Sophie; Sezgin, Efe; Nelson, George W.; Winkler, Cheryl A.] NCI, Basic Res Lab, Ctr Canc Res, Frederick Natl Lab,Leidos Biomed Inc, Frederick, MD 20878 USA.
[Sezgin, Efe] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Fogo, Agnes B.] Vanderbilt Univ, Med Ctr, Dept Pathol Microbiol & Immunol, Div Renal Pathol Electron Microscopy, Nashville, TN USA.
[Goetsch, Stewart] Lancet Pathol Lab, Johannesburg, South Africa.
[Kopp, Jeffrey B.] NIDDK, Kidney Dis Sect, NIH, Bethesda, MD 20892 USA.
[Naicker, Saraladevi] Univ Witwatersrand, Div Nephrol, ZA-2193 Johannesburg, South Africa.
RP Naicker, S (reprint author), Univ Witwatersrand, Fac Hlth Sci, Sch Clin Med, 7 York Rd,Room 4B41, ZA-2193 Johannesburg, South Africa.
EM winklerc@mail.nih.gov; Saraladevi.Naicker@wits.ac.za
RI Sezgin, Efe/B-8418-2012
OI Sezgin, Efe/0000-0002-8000-7485
FU National Institutes of Health (NIH) Fogarty International Center
[1D43TW008330-01A1]; National Institute of Diabetes and Digestive and
Kidney Diseases; Non-communicable Chronic Diseases Leadership Training
Program; Medical Research Council of South Africa; National Research
Foundation of South Africa; National Health Laboratory Service Research
Trust; Columbia University-South Africa Training Program for Research on
AIDS-Related Malignancies; NIH National Cancer Institute
[1D43CA153715-03, HHSN26120080001E]; Division of Nephrology of
University of the Witwatersrand; Faculty Research Committee individual
grant, University of the Witwatersrand; NIH National Cancer Institute
Center for Cancer Research
FX This project was funded by the National Institutes of Health (NIH)
Fogarty International Center (Grant 1D43TW008330-01A1 [July 1, 2010-
June 30, 2015] Millennium Promise Award), the National Institute of
Diabetes and Digestive and Kidney Diseases Intramural Research Programs,
the Non-communicable Chronic Diseases Leadership Training Program, the
Medical Research Council of South Africa, the National Research
Foundation of South Africa, the National Health Laboratory Service
Research Trust, the Columbia University-South Africa Training Program
for Research on AIDS-Related Malignancies, the NIH National Cancer
Institute (Grant 1D43CA153715-03), the Division of Nephrology of
University of the Witwatersrand and the Faculty Research Committee
individual grant, University of the Witwatersrand. This project was also
funded in part with federal funds from the NIH National Cancer Institute
(Contract HHSN26120080001E), and was supported in part by the Intramural
Research Program of the NIH National Cancer Institute Center for Cancer
Research.
NR 41
TC 24
Z9 25
U1 1
U2 5
PU AMER SOC NEPHROLOGY
PI WASHINGTON
PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA
SN 1046-6673
EI 1533-3450
J9 J AM SOC NEPHROL
JI J. Am. Soc. Nephrol.
PD NOV
PY 2015
VL 26
IS 11
BP 2882
EP 2890
DI 10.1681/ASN.2014050469
PG 9
WC Urology & Nephrology
SC Urology & Nephrology
GA CV0CR
UT WOS:000363915500031
PM 25788523
ER
PT J
AU Taylor, J
Hampshire, V
AF Taylor, Joni
Hampshire, Victoria
TI Basic research support for shared magnetic resonance imaging resources
SO LAB ANIMAL
LA English
DT Editorial Material
ID CARE
AB Procedures that enable the collection of longitudinal physiologic and anatomic information can contribute to the reduction and refinement of animal. use. Scientists are increasingly turning to noninvasive magnetic resonance imaging (MRI) to obtain such information from animal research subjects. As they make this important investment, research support veterinarians are often tasked with ensuring the proper care and use of laboratory animal research subjects. A basic understanding of MRI equipment, personnel practices, safety, and monitoring of animals and their recoveries is key to implementing a centralized animal MRI facility.
C1 [Taylor, Joni] NHLBI, Cardiac Energet Lab, NIH, Bethesda, MD 20892 USA.
[Hampshire, Victoria] Capital Preclin Sci Res Consultants LLC, Bethesda, MD 20817 USA.
RP Hampshire, V (reprint author), Capital Preclin Sci Res Consultants LLC, Bethesda, MD 20817 USA.
EM vahampshire@gmail.com
NR 8
TC 1
Z9 1
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0093-7355
EI 1548-4475
J9 LAB ANIMAL
JI Lab Anim.
PD NOV
PY 2015
VL 44
IS 11
BP 435
EP 437
PG 3
WC Veterinary Sciences
SC Veterinary Sciences
GA CV2UL
UT WOS:000364112600016
PM 26484818
ER
PT J
AU Reich, DS
White, R
Cortese, ICM
Vuolo, L
Shea, CD
Collins, TL
Petkau, J
AF Reich, Daniel S.
White, Richard
Cortese, Irene C. M.
Vuolo, Luisa
Shea, Colin D.
Collins, Tassie L.
Petkau, John
TI Sample-size calculations for short-term proof-of-concept studies of
tissue protection and repair in multiple sclerosis lesions via
conventional clinical imaging
SO MULTIPLE SCLEROSIS JOURNAL
LA English
DT Article
DE MRI; T2 lesions; clinical trial design; repair
ID MAGNETIZATION-TRANSFER RATIO; BLOOD-BRAIN-BARRIER; HIGH-FIELD MRI;
SPINAL-CORD; TRIALS; REMYELINATION; EVOLUTION; SERIAL; NEUROPROTECTION;
POSTMORTEM
AB Background: New multiple sclerosis (MS) lesion activity on magnetic resonance imaging (MRI) can test immunomodulatory therapies in proof-of-concept trials. Comparably powerful endpoints to assess tissue protection or repair are lacking.
Objective: The objective of this paper is to report sample-size calculations for assessment of new lesion recovery.
Methods: In two sets of six active MS cases, new lesions were observed by monthly MRI for approximately 12 months. Averages and quartiles of normalized (proton density/T1/T2 weighted) and quantitative (T1/T2 and mean diffusivity maps for dataset 1, T2 and magnetization transfer ratio maps for dataset 2) measures were used to compare the lesion area before lesion appearance to afterward. A linear mixed-effects model incorporating lesion- and participant-specific random effects estimated average levels and variance components for sample-size calculations.
Results: In both datasets, greatest statistical sensitivity was observed for the 25th percentile of normalized proton density-weighted signal. At 3T, using new lesions 15 mm(3), as few as nine participants/arm may be required for a six-month placebo-controlled add-on trial postulating a therapeutic effect size of 20% and statistical power of 90%.
Conclusion: Lesion recovery is a powerful outcome measure for proof-of-concept clinical trials of tissue protection and repair in MS. The trial design requires active cases and is therefore best implemented near disease onset.
C1 [Reich, Daniel S.; Cortese, Irene C. M.; Vuolo, Luisa; Shea, Colin D.] NINDS, Div Neuroimmunol & Neurovirol, NIH, Bethesda, MD 20892 USA.
[White, Richard; Petkau, John] Univ British Columbia, Dept Stat, Vancouver, BC V5Z 1M9, Canada.
[Collins, Tassie L.] Myelin Repair Fdn, Saratoga Springs, NY USA.
RP Reich, DS (reprint author), NINDS, Div Neuroimmunol & Neurovirol, NIH, 10 Ctr Dr MSC 1400,Bldg 10 Room 5C103, Bethesda, MD 20892 USA.
EM reichds@ninds.nih.gov
RI Reich, Daniel/E-5701-2010
OI Reich, Daniel/0000-0002-2628-4334
FU Intramural Research Program of the National Institute of Neurological
Disorders and Stroke; Myelin Repair Foundation
FX This work was supported by the Intramural Research Program of the
National Institute of Neurological Disorders and Stroke and the Myelin
Repair Foundation.
NR 34
TC 5
Z9 5
U1 2
U2 3
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 1352-4585
EI 1477-0970
J9 MULT SCLER J
JI Mult. Scler. J.
PD NOV
PY 2015
VL 21
IS 13
BP 1693
EP 1704
DI 10.1177/1352458515569098
PG 12
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA CV3LP
UT WOS:000364161000010
PM 25662351
ER
PT J
AU Kumari, D
Hayward, B
Nakamura, AJ
Bonner, WM
Usdin, K
AF Kumari, Daman
Hayward, Bruce
Nakamura, Asako J.
Bonner, William M.
Usdin, Karen
TI Evidence for chromosome fragility at the frataxin locus in Friedreich
ataxia
SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS
LA English
DT Article
DE Friedreich ataxia; FXN; Frataxin; Repeat expansion; GAA/TTC-triplet
repeat; Chromosome fragility
ID X-SYNDROME; REPEAT EXPANSION; SITE STABILITY; GENOME-WIDE; TRANSCRIPTION
ELONGATION; DELAYED REPLICATION; PARTIAL TETRASOMY-9; EPIGENETIC
CHANGES; CGG REPEATS; DNA
AB Friedreich ataxia (FRDA) is a member of the Repeat Expansion Diseases, a group of genetic conditions resulting from an increase/expansion in the size of a specific tandem array. FRDA results from expansion of a GAA/TTC-tract in the first intron of the frataxin gene (FXN). The disease-associated tandem repeats all form secondary structures that are thought to contribute to the propensity of the repeat to expand. The subset of these diseases that result from a CGG/CCG-repeat expansion, such as Fragile X syndrome, also express a folate-sensitive fragile site coincident with the repeat on the affected chromosome. This chromosome fragility involves the generation of chromosome/chromatid gaps or breaks, or the high frequency loss of one or both copies of the affected gene when cells are grown under folate stress or as we showed previously, in the presence of an inhibitor of the ATM checkpoint kinase. Whether Repeat Expansion Disease loci containing different repeats form similar fragile sites was not known. We show here that the region of chromosome 9 that contains the FXN locus is intrinsically prone to breakage in vivo even in control cells. However, like FXS alleles, FRDA alleles show significantly elevated levels of chromosome abnormalities in the presence of an ATM inhibitor, consistent with the formation of a fragile site. Published by Elsevier B.V.
C1 [Kumari, Daman; Hayward, Bruce; Usdin, Karen] NIDDK, Sect Gene Struct & Dis, Lab Cell & Mol Biol, NIH, Bethesda, MD 20892 USA.
[Nakamura, Asako J.; Bonner, William M.] NCI, Lab Mol Pharmacol, CCR, NIH, Bethesda, MD 20892 USA.
RP Usdin, K (reprint author), NIH, Bldg 8,Room 2A19,8 Ctr Dr MSC 0830, Bethesda, MD 20892 USA.
EM ku@helix.nih.gov
FU Intramural program of the National Institute of Diabetes, Digestive and
Kidney Diseases [DK057808 08]
FX This work was supported by a grant from the Intramural program of the
National Institute of Diabetes, Digestive and Kidney Diseases to KU
(DK057808 08).
NR 60
TC 1
Z9 1
U1 3
U2 7
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0027-5107
EI 1873-135X
J9 MUTAT RES-FUND MOL M
JI Mutat. Res.-Fundam. Mol. Mech. Mutagen.
PD NOV
PY 2015
VL 781
BP 14
EP 21
DI 10.1016/j.mrfmmm.2015.08.007
PG 8
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology
GA CV3LH
UT WOS:000364160200003
PM 26379101
ER
PT J
AU Danjou, F
Zoledziewska, M
Sidore, C
Steri, M
Busonero, F
Maschio, A
Mulas, A
Perseu, L
Barella, S
Porcu, E
Pistis, G
Pitzalis, M
Pala, M
Menzel, S
Metrustry, S
Spector, TD
Leoni, L
Angius, A
Uda, M
Moi, P
Thein, SL
Galanello, R
Abecasis, GR
Schlessinger, D
Sanna, S
Cucca, F
AF Danjou, Fabrice
Zoledziewska, Magdalena
Sidore, Carlo
Steri, Maristella
Busonero, Fabio
Maschio, Andrea
Mulas, Antonella
Perseu, Lucia
Barella, Susanna
Porcu, Eleonora
Pistis, Giorgio
Pitzalis, Maristella
Pala, Mauro
Menzel, Stephan
Metrustry, Sarah
Spector, Timothy D.
Leoni, Lidia
Angius, Andrea
Uda, Manuela
Moi, Paolo
Thein, Swee Lay
Galanello, Renzo
Abecasis, Gonaalo R.
Schlessinger, David
Sanna, Serena
Cucca, Francesco
TI Genome-wide association analyses based on whole-genome sequencing in
Sardinia provide insights into regulation of hemoglobin levels
SO NATURE GENETICS
LA English
DT Article
ID HUMAN GENE-EXPRESSION; RED-BLOOD-CELL; FETAL-HEMOGLOBIN; DEFINITIVE
ERYTHROPOIESIS; TRANSCRIPTION FACTOR; GENOTYPE IMPUTATION; HEMATOPOIETIC
STEM; BETA-THALASSEMIA; GLOBIN GENE; DNASE-II
AB We report genome-wide association study results for the levels of A1, A2 and fetal hemoglobins, analyzed for the first time concurrently. Integrating high-density array genotyping and whole-genome sequencing in a large general population cohort from Sardinia, we detected 23 associations at 10 loci. Five signals are due to variants at previously undetected loci: MPHOSPH9, PLTP-PCIF1, ZFPM1 (FOG1), NFIX and CCND3. Among the signals at known loci, ten are new lead variants and four are new independent signals. Half of all variants also showed pleiotropic associations with different hemoglobins, which further corroborated some of the detected associations and identified features of coordinated hemoglobin species production.
C1 [Danjou, Fabrice; Zoledziewska, Magdalena; Sidore, Carlo; Steri, Maristella; Busonero, Fabio; Maschio, Andrea; Mulas, Antonella; Perseu, Lucia; Porcu, Eleonora; Pistis, Giorgio; Pitzalis, Maristella; Pala, Mauro; Angius, Andrea; Uda, Manuela; Sanna, Serena; Cucca, Francesco] CNR, Isti Ric Genet & Biomed, Cagliari, Italy.
[Sidore, Carlo; Busonero, Fabio; Maschio, Andrea; Porcu, Eleonora; Pistis, Giorgio; Abecasis, Gonaalo R.] Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA.
[Sidore, Carlo; Mulas, Antonella; Porcu, Eleonora; Pistis, Giorgio; Cucca, Francesco] Univ Sassari, Dipartimento Sci Biomed, I-07100 Sassari, Italy.
[Busonero, Fabio; Maschio, Andrea] Univ Michigan, DNA Sequencing Core, Ann Arbor, MI 48109 USA.
[Barella, Susanna; Moi, Paolo; Galanello, Renzo] Osped Reg Microcitemie, ASL8, Cagliari, Italy.
[Menzel, Stephan; Thein, Swee Lay] Kings Coll London, Dept Mol Hematol, London, England.
[Metrustry, Sarah; Spector, Timothy D.] Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England.
[Leoni, Lidia; Angius, Andrea] Parco Sci & Tecnol Sardegna, Res & Dev Sardinia CRS4, Ctr Adv Studies, Pula, Italy.
[Moi, Paolo; Galanello, Renzo] Univ Cagliari, Dept Publ Hlth & Clin & Mol Med, Cagliari, Italy.
[Thein, Swee Lay] Kings Coll Hosp Natl Hlth Serv NHS Fdn Trust, Dept Hematol Med, London, England.
[Schlessinger, David] NIA, Genet Lab, NIH, Baltimore, MD 21224 USA.
RP Danjou, F (reprint author), CNR, Isti Ric Genet & Biomed, Cagliari, Italy.
EM fabrice.danjou@irgb.cnr.it; fcucca@uniss.it
RI Angius, Andrea/P-9549-2015; Danjou, Fabrice/D-1563-2014;
OI Angius, Andrea/0000-0003-2596-6461; Danjou, Fabrice/0000-0002-4976-2327;
Mulas, Antonella/0000-0002-6856-1483; MOI, Paolo/0000-0001-7879-8057;
sanna, serena/0000-0002-3768-1749; Pitzalis,
Maristella/0000-0003-4975-6987; Steri, Anna
Maristella/0000-0001-5869-3872
FU US National Institutes of Health (National Institute on Aging); National
Human Genome Research Institute [HG005581, HG005552, HG006513,
HG007022]; National Heart, Lung, and Blood Institute [HL117626]; US
National Institutes of Health, National Institute on Aging
[N01-AG-1-2109, HHSN271201100005C]; Sardinian Autonomous Region
[cRP3-154, 7/2009]; grant FaReBio "Farmaci e Reti Biotecnologiche di
Qualita"; PB05 InterOmics MIUR Flagship Project; Wellcome Trust;
European Community's Seventh Framework Programme (FP7); National
Institute for Health Research (NIHR)-funded BioResource, Clinical
Research Facility and Biomedical Research Centre at Guy's and St Thomas'
NHS Foundation Trust; Medical Research Council, UK [G0000111, ID51640];
British Society for Haematology; US National Institutes of Health
(National Heart, Lung, and Blood Institute); US National Institutes of
Health (National Human Genome Research Institute); King's College London
FX This work is dedicated to Antonio Cao, Renzo Galanello and Maurizio
Longinotti, who devoted their scientific lives to understanding,
preventing and treating hematological diseases in Sardinia. We are also
grateful to M.S. Ristaldi and M.G. Marini for knowledge and insight that
they freely shared with us. Finally, we thank all the volunteers who
generously participated in this study and made this research possible.
The SardiNIA study was funded in part by the US National Institutes of
Health (National Institute on Aging, National Heart, Lung, and Blood
Institute, and). This research was supported by National Human Genome
Research Institute grants HG005581, HG005552, HG006513 and HG007022; by
National Heart, Lung, and Blood Institute grant HL117626; by the
Intramural Research Program of the US National Institutes of Health,
National Institute on Aging, contracts N01-AG-1-2109 and
HHSN271201100005C; by Sardinian Autonomous Region (L.R. number 7/2009)
grant cRP3-154; by grant FaReBio2011 "Farmaci e Reti Biotecnologiche di
Qualita"; and by the PB05 InterOmics MIUR Flagship Project. The TwinsUK
study was funded by the Wellcome Trust; the European Community's Seventh
Framework Programme (FP7/2007-2013); and the National Institute for
Health Research (NIHR)-funded BioResource, Clinical Research Facility
and Biomedical Research Centre based at Guy's and St Thomas' NHS
Foundation Trust in partnership with King's College London. Genotyping
in the replication cohorts was performed by the Wellcome Trust Sanger
Institute and National Eye Institute via the US National Institutes of
Health/Center for Inherited Disease Research (CIDR). S.L.T. was
supported by the Medical Research Council, UK (grant G0000111, ID51640),
and S. Menzel received funding from the British Society for Haematology
(start-up grant).
NR 82
TC 8
Z9 8
U1 2
U2 16
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1061-4036
EI 1546-1718
J9 NAT GENET
JI Nature Genet.
PD NOV
PY 2015
VL 47
IS 11
BP 1264
EP +
DI 10.1038/ng.3307
PG 10
WC Genetics & Heredity
SC Genetics & Heredity
GA CV1BN
UT WOS:000363988200010
PM 26366553
ER
PT J
AU Sidore, C
Busonero, F
Maschio, A
Porcu, E
Naitza, S
Zoledziewska, M
Mulas, A
Pistis, G
Steri, M
Danjou, F
Kwong, A
del Vecchyo, VDO
Chiang, CWK
Bragg-Gresham, J
Pitzalis, M
Nagaraja, R
Tarrier, B
Brennan, C
Uzzau, S
Fuchsberger, C
Atzeni, R
Reinier, F
Berutti, R
Huang, J
Timpson, NJ
Toniolo, D
Gasparini, P
Malerba, G
Dedoussis, G
Zeggini, E
Soranzo, N
Jones, C
Lyons, R
Angius, A
Kang, HM
Novembre, J
Sanna, S
Schlessinger, D
Cucca, F
Abecasis, GR
AF Sidore, Carlo
Busonero, Fabio
Maschio, Andrea
Porcu, Eleonora
Naitza, Silvia
Zoledziewska, Magdalena
Mulas, Antonella
Pistis, Giorgio
Steri, Maristella
Danjou, Fabrice
Kwong, Alan
del Vecchyo, Vicente Diego Ortega
Chiang, Charleston W. K.
Bragg-Gresham, Jennifer
Pitzalis, Maristella
Nagaraja, Ramaiah
Tarrier, Brendan
Brennan, Christine
Uzzau, Sergio
Fuchsberger, Christian
Atzeni, Rossano
Reinier, Frederic
Berutti, Riccardo
Huang, Jie
Timpson, Nicholas J.
Toniolo, Daniela
Gasparini, Paolo
Malerba, Giovanni
Dedoussis, George
Zeggini, Eleftheria
Soranzo, Nicole
Jones, Chris
Lyons, Robert
Angius, Andrea
Kang, Hyun M.
Novembre, John
Sanna, Serena
Schlessinger, David
Cucca, Francesco
Abecasis, Goncalo R.
TI Genome sequencing elucidates Sardinian genetic architecture and augments
association analyses for lipid and blood inflammatory markers
SO NATURE GENETICS
LA English
DT Article
ID RARE VARIANT ASSOCIATION; MAPPING COMPLEX TRAITS; C-REACTIVE PROTEIN;
WIDE ASSOCIATION; GENOTYPE IMPUTATION; BETA-THALASSEMIA; DEMOGRAPHIC
HISTORY; MULTIPLE-SCLEROSIS; HEART-DISEASE; POPULATION
AB We report similar to 17.6 million genetic variants from whole-genome sequencing of 2,120 Sardinians; 22% are absent from previous sequencing-based compilations and are enriched for predicted functional consequences. Furthermore, similar to 76,000 variants common in our sample (frequency >5%) are rare elsewhere (<0.5% in the 1000 Genomes Project). We assessed the impact of these variants on circulating lipid levels and five inflammatory biomarkers. We observe 14 signals, including 2 major new loci, for lipid levels and 19 signals, including 2 new loci, for inflammatory markers. The new associations would have been missed in analyses based on 1000 Genomes Project data, underlining the advantages of large-scale sequencing in this founder population.
C1 [Sidore, Carlo; Busonero, Fabio; Maschio, Andrea; Porcu, Eleonora; Naitza, Silvia; Zoledziewska, Magdalena; Mulas, Antonella; Pistis, Giorgio; Steri, Maristella; Danjou, Fabrice; Pitzalis, Maristella; Angius, Andrea; Sanna, Serena; Cucca, Francesco] CNR, Ist Ric Genet & Biomed, Cagliari, Italy.
[Sidore, Carlo; Busonero, Fabio; Maschio, Andrea; Porcu, Eleonora; Pistis, Giorgio; Kwong, Alan; Bragg-Gresham, Jennifer; Fuchsberger, Christian; Kang, Hyun M.; Abecasis, Goncalo R.] Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA.
[Sidore, Carlo; Porcu, Eleonora; Mulas, Antonella; Pistis, Giorgio; Berutti, Riccardo; Cucca, Francesco] Univ Sassari, Dipartimento Sci Biomed, I-07100 Sassari, Italy.
[Busonero, Fabio; Maschio, Andrea; Tarrier, Brendan; Brennan, Christine; Lyons, Robert] Univ Michigan, DNA Sequencing Core, Ann Arbor, MI 48109 USA.
[del Vecchyo, Vicente Diego Ortega] Univ Calif Los Angeles, Interdept Program Bioinformat, Los Angeles, CA USA.
[Chiang, Charleston W. K.] Univ Calif Los Angeles, Dept Ecol & Evolutionary Biol, Los Angeles, CA USA.
[Nagaraja, Ramaiah; Schlessinger, David] NIA, Genet Lab, NIH, Baltimore, MD 21224 USA.
[Uzzau, Sergio] Porto Conte Ric, Tramariglio, Alghero, Italy.
[Atzeni, Rossano; Reinier, Frederic; Berutti, Riccardo; Jones, Chris; Angius, Andrea] Parco Sci & Tecnol Sardegna, Res & Dev Sardinia CRS4, Ctr Adv Studies, Pula, Italy.
[Huang, Jie; Zeggini, Eleftheria; Soranzo, Nicole] Wellcome Trust Sanger Inst, Human Genet, Hinxton, England.
[Timpson, Nicholas J.] Univ Bristol, Integrat Epidemiol Unit, MRC, Bristol, Avon, England.
[Toniolo, Daniela] Ist Sci San Raffaele, Div Genet & Cell Biol, I-20132 Milan, Italy.
[Gasparini, Paolo] Univ Trieste, Dipartimento Salute Mentale, Trieste, Italy.
[Gasparini, Paolo] Burlo Garofolo Children Hosp, Ist Ricovero & Cura Carattere Sci, Trieste, Italy.
[Gasparini, Paolo] Sidra, Expt Genet Div, Doha, Qatar.
[Malerba, Giovanni] Univ Verona, Dept Life & Reprod Sci, I-37100 Verona, Italy.
[Dedoussis, George] Harokopio Univ Athens, Dept Nutr & Dietet, Athens, Greece.
[Soranzo, Nicole] Univ Cambridge, Dept Haematol, Cambridge, England.
[Novembre, John] Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA.
RP Cucca, F (reprint author), CNR, Ist Ric Genet & Biomed, Cagliari, Italy.
EM fcucca@uniss.it; goncalo@umich.edu
RI Angius, Andrea/P-9549-2015; Fox, Laura /C-6249-2016; Danjou,
Fabrice/D-1563-2014; Naitza, Silvia/D-5620-2017;
OI Steri, Anna Maristella/0000-0001-5869-3872; Soranzo,
Nicole/0000-0003-1095-3852; Angius, Andrea/0000-0003-2596-6461; Danjou,
Fabrice/0000-0002-4976-2327; Fuchsberger, Christian/0000-0002-5918-8947;
Sidore, Carlo/0000-0001-7504-7477; Malerba,
Giovanni/0000-0001-8705-8560; sanna, serena/0000-0002-3768-1749; Mulas,
Antonella/0000-0002-6856-1483; Pitzalis, Maristella/0000-0003-4975-6987;
Chiang, Charleston/0000-0002-0668-7865; Timpson,
Nicholas/0000-0002-7141-9189
FU National Human Genome Research Institute [HG005581, HG005552, HG006513,
HG007022, HG007089]; National Heart, Lung, and Blood Institute
[HL117626]; US National Institutes of Health, National Institute on
Aging [N01-AG-1-2109, HHSN271201100005C]; Sardinian Autonomous Region
[cRP3-154]; InterOmics MIUR Flagship Project [PB05]; FaReBio 'Farmaci e
Reti Biotecnologiche di Qualita'; US National Institutes of Health
National Research Service Award (NRSA) [F32GM106656]; UC MEXUS/CONOCYT
fellowship; Wellcome Trust [WT091310, WT098051, 098051,
WT091310/C/10/Z]; European Union [257082, HEALTH-F5-2011-282510];
National Institute for Health Research (NIHR) British Research Council
(BRC); Ministero della Salute-Ricerca Finalizzata [PE-2011-02347500];
Fondazione Cariplo (Italy); Ministry of Health; Public Health Genomics
Project; European Research Council [ERC-2011-StG 280559-SEPI]; Ricerca
Finalizzata (Italy)
FX We thank all the volunteers who generously participated in this study
and made this research possible. This research was supported by National
Human Genome Research Institute grants HG005581, HG005552, HG006513,
HG007022 and HG007089; by National Heart, Lung, and Blood Institute
grant HL117626; by the Intramural Research Program of the US National
Institutes of Health, National Institute on Aging, contracts
N01-AG-1-2109 and HHSN271201100005C; by Sardinian Autonomous Region
(L.R. 7/2009) grant cRP3-154; by the PB05 InterOmics MIUR Flagship
Project; by grant FaReBio2011 'Farmaci e Reti Biotecnologiche di
Qualita'; by a US National Institutes of Health National Research
Service Award (NRSA) postdoctoral fellowship (F32GM106656) to C.W.K.C.;
and by the UC MEXUS/CONOCYT fellowship to V.D.O.d.V. The replication
cohorts acknowledge the use of data generated by the UK10K Consortium,
supported by Wellcome Trust award WT091310. The UK10K research was
specifically funded by a Wellcome Trust award, '10,000 UK Genome
Sequences: Accessing the Role of Rare Genetic Variants in Health and
Disease' (WT091310/C/10/Z). The research of N.S. is supported by the
Wellcome Trust (grants WT098051 and WT091310), the European Union's
Seventh Framework Programme (EPIGENESYS grant 257082 and BLUEPRINT grant
HEALTH-F5-2011-282510) and the National Institute for Health Research
(NIHR) British Research Council (BRC). The ING-FVG cohort was supported
by grant Ministero della Salute-Ricerca Finalizzata PE-2011-02347500 (to
P.G.); the ING-VB study thanks the inhabitants of Val Borbera for
participating in the study, M. Traglia, C. Sala and C. Masciullo for
data management, and the funding sources Fondazione Cariplo (Italy), the
Ministry of Health, Ricerca Finalizzata (Italy) 2008, 2011-2012, and the
Public Health Genomics Project 2010. The HELIC cohorts are thankful to
the residents of the Pomak villages and the Mylopotamos villages for
participating and to their funding sources, including the Wellcome Trust
(098051) and the European Research Council (ERC-2011-StG 280559-SEPI).
NR 76
TC 20
Z9 20
U1 2
U2 11
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1061-4036
EI 1546-1718
J9 NAT GENET
JI Nature Genet.
PD NOV
PY 2015
VL 47
IS 11
BP 1272
EP +
DI 10.1038/ng.3368
PG 13
WC Genetics & Heredity
SC Genetics & Heredity
GA CV1BN
UT WOS:000363988200011
PM 26366554
ER
PT J
AU Day, FR
Ruth, KS
Thompson, DJ
Lunetta, KL
Pervjakova, N
Chasman, DI
Stolk, L
Finucane, HK
Sulem, P
Bulik-Sullivan, B
Esko, T
Johnson, AD
Elks, CE
Franceschini, N
He, CY
Altmaier, E
Brody, JA
Franke, LL
Huffman, JE
Keller, MF
McArdle, PF
Nutile, T
Porcu, E
Robino, A
Rose, LM
Schick, UM
Smith, JA
Teumer, A
Traglia, M
Vuckovic, D
Yao, J
Zhao, W
Albrecht, E
Amin, N
Corre, T
Hottenga, JJ
Mangino, M
Smith, AV
Tanaka, T
Abecasis, GR
Andrulis, IL
Anton-Culver, H
Antoniou, AC
Arndt, V
Arnold, AM
Barbieri, C
Beckmann, MW
Beeghly-Fadiel, A
Benitez, J
Bernstein, L
Bielinski, SJ
Blomqvist, C
Boerwinkle, E
Bogdanova, NV
Bojesen, SE
Bolla, MK
Borresen-Dale, AL
Boutin, TS
Brauch, H
Brenner, H
Bruning, T
Burwinkel, B
Campbell, A
Campbell, H
Chanock, SJ
Chapman, JR
Chen, YDI
Chenevix-Trench, G
Couch, FJ
Coviello, AD
Cox, A
Czene, K
Darabi, H
De Vivo, I
Demerath, EW
Dennis, J
Devilee, P
Dork, T
Dos-Santos-Silva, I
Dunning, AM
Eicher, JD
Fasching, PA
Faul, JD
Figueroa, J
Flesch-Janys, D
Gandin, I
Garcia, ME
Garcia-Closas, M
Giles, GG
Girotto, GG
Goldberg, MS
Gonzalez-Neira, A
Goodarzi, MO
Grove, ML
Gudbjartsson, DF
Guenel, P
Guo, XQ
Haiman, CA
Hall, P
Hamann, U
Henderson, BE
Hocking, LJ
Hofman, A
Homuth, G
Hooning, MJ
Hopper, JL
Hu, FB
Huang, JY
Humphreys, K
Hunter, DJ
Jakubowska, A
Jones, SE
Kabisch, M
Karasik, D
Knight, JA
Kolcic, I
Kooperberg, C
Kosma, VM
Kriebel, J
Kristensen, V
Lambrechts, D
Langenberg, C
Li, JM
Li, X
Lindstrom, S
Liu, YM
Luan, JN
Lubinski, J
Magi, R
Mannermaa, A
Manz, J
Margolin, S
Marten, J
Martin, NG
Masciullo, C
Meindl, A
Michailidou, K
Mihailov, E
Milani, L
Milne, RL
Muller-Nurasyid, M
Nalls, M
Neale, BM
Nevanlinna, H
Neven, P
Newman, AB
Nordestgaard, BG
Olson, JE
Padmanabhan, S
Peterlongo, P
Peters, U
Petersmann, A
Peto, J
Pharoah, PDP
Pirastu, NN
Pirie, A
Pistis, G
Polasek, O
Porteous, D
Psaty, BM
Pylkas, K
Radice, P
Raffel, LJ
Rivadeneira, F
Rudan, I
Rudolph, A
Ruggiero, D
Sala, CF
Sanna, S
Sawyer, EJ
Schlessinger, D
Schmidt, MK
Schmidt, F
Schmutzler, RK
Schoemaker, MJ
Scott, RA
Seynaeve, CM
Simard, J
Sorice, R
Southey, MC
Stockl, D
Strauch, K
Swerdlow, A
Taylor, KD
Thorsteinsdottir, U
Toland, AE
Tomlinson, I
Truong, T
Tryggvadottir, L
Turner, ST
Vozzi, D
Wang, Q
Wellons, M
Willemsen, G
Wilson, JF
Winqvist, R
Wolffenbuttel, BBHR
Wright, AF
Yannoukakos, D
Zemunik, T
Zheng, W
Zygmunt, M
Bergmann, S
Boomsma, DI
Buring, JE
Ferrucci, L
Montgomery, GW
Gudnason, V
Spector, TD
van Duijn, CM
Alizadeh, BZ
Ciullo, M
Crisponi, L
Easton, DF
Gasparini, PP
Gieger, C
Harris, TB
Hayward, C
Kardia, SLR
Kraft, P
McKnight, B
Metspalu, A
Morrison, AC
Reiner, AP
Ridker, PM
Rotter, JI
Toniolo, D
Uitterlinden, AG
Ulivi, S
Volzke, H
Wareham, NJ
Weir, DR
Yerges-Armstrong, LM
Price, AL
Stefansson, K
Visser, JA
Ong, KK
Chang-Claude, J
Murabito, JM
Perry, JRB
Murray, A
AF Day, Felix R.
Ruth, Katherine S.
Thompson, Deborah J.
Lunetta, Kathryn L.
Pervjakova, Natalia
Chasman, Daniel I.
Stolk, Lisette
Finucane, Hilary K.
Sulem, Patrick
Bulik-Sullivan, Brendan
Esko, Tonu
Johnson, Andrew D.
Elks, Cathy E.
Franceschini, Nora
He, Chunyan
Altmaier, Elisabeth
Brody, Jennifer A.
Franke, Lude L.
Huffman, Jennifer E.
Keller, Margaux F.
McArdle, Patrick F.
Nutile, Teresa
Porcu, Eleonora
Robino, Antonietta
Rose, Lynda M.
Schick, Ursula M.
Smith, Jennifer A.
Teumer, Alexander
Traglia, Michela
Vuckovic, Dragana
Yao, Jie
Zhao, Wei
Albrecht, Eva
Amin, Najaf
Corre, Tanguy
Hottenga, Jouke-Jan
Mangino, Massimo
Smith, Albert V.
Tanaka, Toshiko
Abecasis, Goncalo R.
Andrulis, Irene L.
Anton-Culver, Hoda
Antoniou, Antonis C.
Arndt, Volker
Arnold, Alice M.
Barbieri, Caterina
Beckmann, Matthias W.
Beeghly-Fadiel, Alicia
Benitez, Javier
Bernstein, Leslie
Bielinski, Suzette J.
Blomqvist, Carl
Boerwinkle, Eric
Bogdanova, Natalia V.
Bojesen, Stig E.
Bolla, Manjeet K.
Borresen-Dale, Anne-Lise
Boutin, Thibaud S.
Brauch, Hiltrud
Brenner, Hermann
Bruening, Thomas
Burwinkel, Barbara
Campbell, Archie
Campbell, Harry
Chanock, Stephen J.
Chapman, J. Ross
Chen, Yii-Der Ida
Chenevix-Trench, Georgia
Couch, Fergus J.
Coviello, Andrea D.
Cox, Angela
Czene, Kamila
Darabi, Hatef
De Vivo, Immaculata
Demerath, Ellen W.
Dennis, Joe
Devilee, Peter
Doerk, Thilo
dos-Santos-Silva, Isabel
Dunning, Alison M.
Eicher, John D.
Fasching, Peter A.
Faul, Jessica D.
Figueroa, Jonine
Flesch-Janys, Dieter
Gandin, Ilaria
Garcia, Melissa E.
Garcia-Closas, Montserrat
Giles, Graham G.
Girotto, Giorgia G.
Goldberg, Mark S.
Gonzalez-Neira, Anna
Goodarzi, Mark O.
Grove, Megan L.
Gudbjartsson, Daniel F.
Guenel, Pascal
Guo, Xiuqing
Haiman, Christopher A.
Hall, Per
Hamann, Ute
Henderson, Brian E.
Hocking, Lynne J.
Hofman, Albert
Homuth, Georg
Hooning, Maartje J.
Hopper, John L.
Hu, Frank B.
Huang, Jinyan
Humphreys, Keith
Hunter, David J.
Jakubowska, Anna
Jones, Samuel E.
Kabisch, Maria
Karasik, David
Knight, Julia A.
Kolcic, Ivana
Kooperberg, Charles
Kosma, Veli-Matti
Kriebel, Jennifer
Kristensen, Vessela
Lambrechts, Diether
Langenberg, Claudia
Li, Jingmei
Li, Xin
Lindstroem, Sara
Liu, Yongmei
Luan, Jian'an
Lubinski, Jan
Maegi, Reedik
Mannermaa, Arto
Manz, Judith
Margolin, Sara
Marten, Jonathan
Martin, Nicholas G.
Masciullo, Corrado
Meindl, Alfons
Michailidou, Kyriaki
Mihailov, Evelin
Milani, Lili
Milne, Roger L.
Mueller-Nurasyid, Martina
Nalls, Michael
Neale, Benjamin M.
Nevanlinna, Heli
Neven, Patrick
Newman, Anne B.
Nordestgaard, Borge G.
Olson, Janet E.
Padmanabhan, Sandosh
Peterlongo, Paolo
Peters, Ulrike
Petersmann, Astrid
Peto, Julian
Pharoah, Paul D. P.
Pirastu, Nicola N.
Pirie, Ailith
Pistis, Giorgio
Polasek, Ozren
Porteous, David
Psaty, Bruce M.
Pylkas, Katri
Radice, Paolo
Raffel, Leslie J.
Rivadeneira, Fernando
Rudan, Igor
Rudolph, Anja
Ruggiero, Daniela
Sala, Cinzia F.
Sanna, Serena
Sawyer, Elinor J.
Schlessinger, David
Schmidt, Marjanka K.
Schmidt, Frank
Schmutzler, Rita K.
Schoemaker, Minouk J.
Scott, Robert A.
Seynaeve, Caroline M.
Simard, Jacques
Sorice, Rossella
Southey, Melissa C.
Stoeckl, Doris
Strauch, Konstantin
Swerdlow, Anthony
Taylor, Kent D.
Thorsteinsdottir, Unnur
Toland, Amanda E.
Tomlinson, Ian
Truong, Therese
Tryggvadottir, Laufey
Turner, Stephen T.
Vozzi, Diego
Wang, Qin
Wellons, Melissa
Willemsen, Gonneke
Wilson, James F.
Winqvist, Robert
Wolffenbuttel, Bruce B. H. R.
Wright, Alan F.
Yannoukakos, Drakoulis
Zemunik, Tatijana
Zheng, Wei
Zygmunt, Marek
Bergmann, Sven
Boomsma, Dorret I.
Buring, Julie E.
Ferrucci, Luigi
Montgomery, Grant W.
Gudnason, Vilmundur
Spector, Tim D.
van Duijn, Cornelia M.
Alizadeh, Behrooz Z.
Ciullo, Marina
Crisponi, Laura
Easton, Douglas F.
Gasparini, Paolo P.
Gieger, Christian
Harris, Tamara B.
Hayward, Caroline
Kardia, Sharon L. R.
Kraft, Peter
McKnight, Barbara
Metspalu, Andres
Morrison, Alanna C.
Reiner, Alex P.
Ridker, Paul M.
Rotter, Jerome I.
Toniolo, Daniela
Uitterlinden, Andre G.
Ulivi, Sheila
Voelzke, Henry
Wareham, Nicholas J.
Weir, David R.
Yerges-Armstrong, Laura M.
Price, Alkes L.
Stefansson, Kari
Visser, Jenny A.
Ong, Ken K.
Chang-Claude, Jenny
Murabito, Joanne M.
Perry, John R. B.
Murray, Anna
CA EPIC-InterAct Consortium
LifeLines Cohort Study
TI Large-scale genomic analyses link reproductive aging to hypothalamic
signaling, breast cancer susceptibility and BRCA1-mediated DNA repair
SO NATURE GENETICS
LA English
DT Article
ID PREMATURE OVARIAN FAILURE; BRCA2 MUTATION CARRIERS; BODY-MASS INDEX;
NATURAL MENOPAUSE; HOMOLOGOUS RECOMBINATION; CHROMOSOMAL INSTABILITY;
WIDE ASSOCIATION; BLOOD-PRESSURE; CELL-TYPES; LOCI
AB Menopause timing has a substantial impact on infertility and risk of disease, including breast cancer, but the underlying mechanisms are poorly understood. We report a dual strategy in similar to 70,000 women to identify common and low-frequency protein-coding variation associated with age at natural menopause (ANM). We identified 44 regions with common variants, including two regions harboring additional rare missense alleles of large effect. We found enrichment of signals in or near genes involved in delayed puberty, highlighting the first molecular links between the onset and end of reproductive lifespan. Pathway analyses identified major association with DNA damage response (DDR) genes, including the first common coding variant in BRCA1 associated with any complex trait. Mendelian randomization analyses supported a causal effect of later ANM on breast cancer risk (similar to 6% increase in risk per year; P = 3 x 10(-14)), likely mediated by prolonged sex hormone exposure rather than DDR mechanisms.
C1 [Day, Felix R.; Elks, Cathy E.; Langenberg, Claudia; Luan, Jian'an; Scott, Robert A.; Wareham, Nicholas J.; Ong, Ken K.; Perry, John R. B.] Univ Cambridge, MRC, Epidemiol Unit, Sch Clin Med,Inst Metab Sci, Cambridge, England.
[Ruth, Katherine S.; Jones, Samuel E.; Murray, Anna] Univ Exeter, Sch Med, Genet Complex Traits, Exeter, Devon, England.
[Thompson, Deborah J.; Antoniou, Antonis C.; Bolla, Manjeet K.; Dennis, Joe; Michailidou, Kyriaki; Pharoah, Paul D. P.; Pirie, Ailith; Wang, Qin; Easton, Douglas F.] Univ Cambridge, Dept Publ Hlth & Primary Care, Ctr Canc Genet Epidemiol, Cambridge, England.
[Lunetta, Kathryn L.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Lunetta, Kathryn L.; Johnson, Andrew D.; Huffman, Jennifer E.; Eicher, John D.; Murabito, Joanne M.] NHLBI, Framingham, MA USA.
[Lunetta, Kathryn L.; Johnson, Andrew D.; Huffman, Jennifer E.; Eicher, John D.; Murabito, Joanne M.] Boston Univ, Framingham Heart Study, Framingham, MA USA.
[Pervjakova, Natalia; Esko, Tonu; Maegi, Reedik; Mihailov, Evelin; Milani, Lili; Metspalu, Andres] Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia.
[Pervjakova, Natalia] Univ Tartu, Inst Mol & Cell Biol, EE-50090 Tartu, Estonia.
[Chasman, Daniel I.; Rose, Lynda M.; Buring, Julie E.; Ridker, Paul M.] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA.
[Chasman, Daniel I.; Karasik, David; Buring, Julie E.; Ridker, Paul M.] Harvard Univ, Sch Med, Boston, MA USA.
[Stolk, Lisette; Rivadeneira, Fernando; Uitterlinden, Andre G.; Visser, Jenny A.] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands.
[Stolk, Lisette; Rivadeneira, Fernando; Uitterlinden, Andre G.] Netherlands Consortium Hlth Aging, Leiden, Netherlands.
[Stolk, Lisette; Rivadeneira, Fernando; Uitterlinden, Andre G.] Natl Genom Initiat, Leiden, Netherlands.
[Finucane, Hilary K.; De Vivo, Immaculata; Hu, Frank B.; Hunter, David J.; Li, Xin; Lindstroem, Sara; Kraft, Peter; Price, Alkes L.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Finucane, Hilary K.] MIT, Dept Math, Cambridge, MA 02139 USA.
[Sulem, Patrick; Gudbjartsson, Daniel F.; Thorsteinsdottir, Unnur; Stefansson, Kari] deCODE Genet Amgen Inc, Reykjavik, Iceland.
[Bulik-Sullivan, Brendan; Neale, Benjamin M.] Broad Inst MIT & Harvard, Stanley Ctr Psychiat Res, Cambridge, MA 02139 USA.
[Bulik-Sullivan, Brendan; Neale, Benjamin M.] Massachusetts Gen Hosp, Dept Med, Analyt & Translat Genet Unit, Boston, MA 02114 USA.
[Bulik-Sullivan, Brendan; Neale, Benjamin M.] Broad Inst, Med & Populat Genet, Cambridge, MA USA.
[Esko, Tonu] Boston Childrens Hosp, Div Endocrinol, Boston, MA USA.
[Esko, Tonu] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA.
[Esko, Tonu; Hunter, David J.] Broad Inst MIT & Harvard, Cambridge, MA USA.
[Franceschini, Nora] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA.
[He, Chunyan] Indiana Univ, Richard M Fairbanks Sch Publ Hlth, Dept Epidemiol, Indianapolis, IN 46204 USA.
[He, Chunyan] Indiana Univ, Melvin & Bren Simon Canc Ctr, Indianapolis, IN 46204 USA.
[Altmaier, Elisabeth; Kriebel, Jennifer; Manz, Judith] Helmholtz Zentrum Munchen, German Res Ctr Environm Hlth, Res Unit Mol Epidemiol, Neuherberg, Germany.
[Altmaier, Elisabeth; Albrecht, Eva; Mueller-Nurasyid, Martina; Strauch, Konstantin] Helmholtz Zenntrum Munchen, German Res Ctr Environm Hlth, Inst Genet Epidemiol, Neuherberg, Germany.
[Brody, Jennifer A.; Psaty, Bruce M.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA.
[Franke, Lude L.] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, Groningen, Netherlands.
[Huffman, Jennifer E.; Boutin, Thibaud S.; Marten, Jonathan; Wilson, James F.; Wright, Alan F.; Hayward, Caroline] Univ Edinburgh, Human Genet Unit, MRC, Inst Genet & Mol Med, Edinburgh EH8 9YL, Midlothian, Scotland.
[Keller, Margaux F.] Merck Pharmaceut, Boston, MA USA.
[McArdle, Patrick F.; Yerges-Armstrong, Laura M.] Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, Program Personalized Med, Baltimore, MD 21201 USA.
[Nutile, Teresa; Ruggiero, Daniela; Sorice, Rossella; Ciullo, Marina] CNR, Inst Genet & Biophys, Naples, Italy.
[Porcu, Eleonora; Pistis, Giorgio; Sanna, Serena; Crisponi, Laura] CNR, Inst Genet & Biomed Res, Cagliari, Italy.
[Porcu, Eleonora; Pistis, Giorgio] Univ Sassari, Dept Biomed Sci, I-07100 Sassari, Italy.
[Porcu, Eleonora; Abecasis, Goncalo R.; Pistis, Giorgio] Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA.
[Robino, Antonietta; Vuckovic, Dragana; Barbieri, Caterina; Gandin, Ilaria; Pirastu, Nicola N.; Vozzi, Diego; Gasparini, Paolo P.; Ulivi, Sheila] Sci Inst Res Hospitalisat & Hlth Care Burlo Garof, Inst Maternal & Child Hlth, Trieste, Italy.
[Schick, Ursula M.; Kooperberg, Charles; Peters, Ulrike; Reiner, Alex P.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA.
[Smith, Jennifer A.; Zhao, Wei; Kardia, Sharon L. R.] Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA.
[Teumer, Alexander; Voelzke, Henry] Univ Med Greifswald, Inst Community Med, Greifswald, Germany.
[Traglia, Michela; Barbieri, Caterina; Masciullo, Corrado; Sala, Cinzia F.; Toniolo, Daniela] Ist Sci San Raffaele, Div Genet & Cell Biol, I-20132 Milan, Italy.
[Vuckovic, Dragana; Gandin, Ilaria; Girotto, Giorgia G.; Pirastu, Nicola N.; Gasparini, Paolo P.] Univ Trieste, Dept Clin Med Sci Surg & Hlth, Trieste, Italy.
[Yao, Jie; Chen, Yii-Der Ida; Guo, Xiuqing; Taylor, Kent D.; Rotter, Jerome I.] Harbor UCLA Med Ctr, Dept Pediat, Inst Translat Genom & Populat Sci, LABioMed, Torrance, CA 90509 USA.
[Amin, Najaf; Hofman, Albert; Rivadeneira, Fernando; van Duijn, Cornelia M.; Uitterlinden, Andre G.] Erasmus MC, Dept Epidemiol, Genet Epidemiol Unit, Rotterdam, Netherlands.
[Corre, Tanguy; Bergmann, Sven] Univ Lausanne, Dept Med Genet, Lausanne, Switzerland.
[Corre, Tanguy; Bergmann, Sven] Swiss Inst Bioinformat, Lausanne, Switzerland.
[Hottenga, Jouke-Jan; Willemsen, Gonneke; Boomsma, Dorret I.] Vrije Univ Amsterdam, Dept Biol Psychol, Amsterdam, Netherlands.
[Mangino, Massimo; Spector, Tim D.] Kings Coll London, Dept Twin Res & Genet Epidemiol, London WC2R 2LS, England.
[Mangino, Massimo] Guys & St Thomas Fdn Trust, Biomed Res Ctr, Natl Inst Hlth Res, London, England.
[Smith, Albert V.; Gudnason, Vilmundur] Icelandic Heart Assoc, Kopavogur, Iceland.
[Smith, Albert V.; Thorsteinsdottir, Unnur; Gudnason, Vilmundur; Stefansson, Kari] Univ Iceland, Fac Med, Reykjavik, Iceland.
[Tanaka, Toshiko; Ferrucci, Luigi] NIA, Longitudinal Studies Sect, Translat Gerontol Branch, Baltimore, MD 21224 USA.
[Andrulis, Irene L.] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Toronto, ON M5G 1X5, Canada.
[Andrulis, Irene L.] Univ Toronto, Dept Mol Genet, Toronto, ON, Canada.
[Anton-Culver, Hoda] Univ Calif Irvine, Dept Epidemiol, Irvine, CA USA.
[Arndt, Volker; Brenner, Hermann] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany.
[Arnold, Alice M.; McKnight, Barbara] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Beckmann, Matthias W.; Fasching, Peter A.] Univ Erlangen Nurnberg, Univ Hosp Erlangen, Dept Obstet & Gynaecol, D-91054 Erlangen, Germany.
[Beeghly-Fadiel, Alicia; Zheng, Wei] Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Div Epidemiol,Dept Med, Nashville, TN 37212 USA.
[Benitez, Javier; Gonzalez-Neira, Anna] Spanish Natl Canc Res Ctr CNIO, Human Canc Genet Program, Human Genet Grp, Madrid, Spain.
[Benitez, Javier] Ctr Invest Red Enfermedades Raras CIBERER, Valencia, Spain.
[Bernstein, Leslie] City Hope Natl Med Ctr, Beckman Res Inst, Duarte, CA USA.
[Bielinski, Suzette J.; Olson, Janet E.] Mayo Clin, Dept Hlth Sci Res, Div Epidemiol, Rochester, MN USA.
[Blomqvist, Carl] Univ Helsinki, Dept Oncol, Helsinki, Finland.
[Blomqvist, Carl; Nevanlinna, Heli] Univ Helsinki, Cent Hosp, Helsinki, Finland.
[Boerwinkle, Eric; Grove, Megan L.; Morrison, Alanna C.] Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Ctr Human Genet, Houston, TX 77030 USA.
[Boerwinkle, Eric] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA.
[Bogdanova, Natalia V.] Hannover Med Sch, Dept Radiat Oncol, Hannover, Germany.
[Bojesen, Stig E.; Nordestgaard, Borge G.] Univ Copenhagen, Fac Med & Hlth Sci, Copenhagen, Denmark.
[Bojesen, Stig E.; Nordestgaard, Borge G.] Univ Copenhagen, Copenhagen Univ Hosp, Herlev Hosp, Dept Clin Biochem, Copenhagen, Denmark.
[Borresen-Dale, Anne-Lise; Kristensen, Vessela] Oslo Univ Hosp, Radiumhosp, Inst Canc Res, Dept Genet, Oslo, Norway.
[Borresen-Dale, Anne-Lise; Kristensen, Vessela] Univ Oslo, Fac Med, Dept Clin Med, Oslo, Norway.
[Brauch, Hiltrud] Dr Margarete Fischer Bosch Inst Clin Pharmacol, Stuttgart, Germany.
[Brauch, Hiltrud] Univ Tubingen, Inst Clin Pharmacol, Tubingen, Germany.
[Brauch, Hiltrud; Brenner, Hermann] German Canc Res Ctr, German Canc Consortium DKTK, Heidelberg, Germany.
[Brenner, Hermann] German Canc Res Ctr, Div Prevent Oncol, Heidelberg, Germany.
[Bruening, Thomas] Univ Bochum IPA, Inst Ruhr, German Social Accid Insurance, Inst Prevent & Occupat Med, Bochum, Germany.
[Burwinkel, Barbara] German Canc Res Ctr, Div Mol Genet Epidemiol, Heidelberg, Germany.
[Burwinkel, Barbara] Heidelberg Univ, Dept Obstet & Gynecol, Mol Biol Breast Canc, Heidelberg, Germany.
[Campbell, Archie; Porteous, David] Univ Edinburgh, Inst Genet & Mol Med, Ctr Genom & Expt Med, Med Genet Sect, Edinburgh, Midlothian, Scotland.
[Campbell, Harry; Rudan, Igor; Wilson, James F.] Univ Edinburgh, Inst Populat Hlth Sci & Informat, Edinburgh, Midlothian, Scotland.
[Chanock, Stephen J.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Chapman, J. Ross; Tomlinson, Ian] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.
[Chenevix-Trench, Georgia] QIMR Berghofer Med Res Inst, Dept Genet, Brisbane, Qld, Australia.
[Couch, Fergus J.] Mayo Clin, Dept Lab Med & Pathol, Rochester, MI USA.
[Coviello, Andrea D.] Boston Univ, Sch Med, Dept Med, Sect Prevent Med, Boston, MA 02118 USA.
[Coviello, Andrea D.] Boston Univ, Sch Med, Dept Med, Endocrinol Sect, Boston, MA 02118 USA.
[Cox, Angela] Univ Sheffield, Dept Oncol, Sheffield Canc Res, Sheffield, S Yorkshire, England.
[Czene, Kamila; Darabi, Hatef; Hall, Per; Humphreys, Keith; Li, Jingmei] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
[De Vivo, Immaculata; Hu, Frank B.; Hunter, David J.] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA.
[De Vivo, Immaculata; Hu, Frank B.; Hunter, David J.] Harvard Univ, Sch Med, Boston, MA USA.
[Demerath, Ellen W.] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA.
[Devilee, Peter] Leiden Univ, Dept Human Genet, Med Ctr, NL-2300 RA Leiden, Netherlands.
[Devilee, Peter] Leiden Univ, Dept Pathol, Med Ctr, Leiden, Netherlands.
[Doerk, Thilo] Hannover Med Sch, Gynaecol Res Unit, Hannover, Germany.
[dos-Santos-Silva, Isabel; Peto, Julian] London Sch Hyg & Trop Med, Non Communicable Dis Epidemiol Dept, London WC1, England.
[Dunning, Alison M.; Pharoah, Paul D. P.; Easton, Douglas F.] Univ Cambridge, Dept Oncol, Ctr Canc Genet Epidemiol, Cambridge, England.
[Fasching, Peter A.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Div Hematol & Oncol, Los Angeles, CA 90095 USA.
[Faul, Jessica D.; Weir, David R.] Univ Michigan, Inst Social Res, Survey Res Ctr, Ann Arbor, MI USA.
[Figueroa, Jonine] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA.
[Flesch-Janys, Dieter] Univ Clin Hamburg Eppendorf, Clin Canc Registry, Dept Canc Epidemiol, Hamburg, Germany.
[Flesch-Janys, Dieter] Univ Clin Hamburg Eppendorf, Inst Med Biometr & Epidemiol, Hamburg, Germany.
[Garcia, Melissa E.; Harris, Tamara B.] NIA, Lab Epidemiol & Populat Sci, Bethesda, MD 20892 USA.
[Garcia-Closas, Montserrat; Schoemaker, Minouk J.; Swerdlow, Anthony] Inst Canc Res, Div Genet & Epidemiol, London SW3 6JB, England.
[Garcia-Closas, Montserrat] Inst Canc Res, Breakthrough Breast Canc Res Ctr, Div Canc Studies, London SW3 6JB, England.
[Giles, Graham G.; Hopper, John L.; Milne, Roger L.] Univ Melbourne, Melbourne Sch Populat & Global Hlth, Ctr Biostat & Epidemiol, Melbourne, Vic, Australia.
[Giles, Graham G.; Milne, Roger L.] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic, Australia.
[Goldberg, Mark S.] McGill Univ, Dept Med, Montreal, PQ, Canada.
[Goldberg, Mark S.] McGill Univ, Royal Victoria Hosp, Dept Clin Epidemiol, Montreal, PQ H3A 1A1, Canada.
[Goodarzi, Mark O.] Cedars Sinai Med Ctr, Div Endocrinol Diabet & Metab, Los Angeles, CA 90048 USA.
[Gudbjartsson, Daniel F.] Univ Iceland, Sch Engn & Nat Sci, Reykjavik, Iceland.
[Guenel, Pascal; Truong, Therese] INSERM, Ctr Res Epidemiol & Populat Hlth, Environm Epidemiol Canc, Villejuif, France.
[Guenel, Pascal; Truong, Therese] Univ Paris Sud, UMRS 1018, Villejuif, France.
[Haiman, Christopher A.; Henderson, Brian E.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA.
[Hamann, Ute; Kabisch, Maria] German Canc Res Ctr, Mol Genet Breast Canc, Heidelberg, Germany.
[Hocking, Lynne J.] Univ Aberdeen, Div Appl Med, Musculoskeletal Res Programme, Aberdeen, Scotland.
[Homuth, Georg; Schmidt, Frank] Univ Med Greifswald, Interfac Inst Genet & Funct Gen, Greifswald, Germany.
[Hooning, Maartje J.; Seynaeve, Caroline M.] Erasmus Univ, Med Ctr, Dept Med Oncol, Rotterdam, Netherlands.
[Hu, Frank B.; Hunter, David J.] Harvard Univ, Sch Med, Dept Nutr, Boston, MA USA.
[Huang, Jinyan] Shanghai Jiao Tong Univ, Sch Med, Rui Jin Hosp, State Key Lab Med Genom,Shanghai Inst Hematol, Shanghai 200030, Peoples R China.
[Jakubowska, Anna; Lubinski, Jan] Pomeranian Med Univ, Dept Genet & Pathol, Szczecin, Poland.
[Karasik, David] Hebrew SeniorLife Inst Aging Res, Boston, MA USA.
[Knight, Julia A.] Mt Sinai Hosp, Lunenfeld Tanenbaum Res Inst, Prosserman Ctr Hlth Res, Toronto, ON M5G 1X5, Canada.
[Knight, Julia A.] Univ Toronto, Dalla Lana Sch Publ Hlth, Div Epidemiol, Toronto, ON, Canada.
[Kolcic, Ivana; Polasek, Ozren; Zemunik, Tatijana] Univ Split, Fac Med, Split, Croatia.
[Kosma, Veli-Matti; Mannermaa, Arto] Kuopio Univ Hosp, Ctr Canc, SF-70210 Kuopio, Finland.
[Kosma, Veli-Matti; Mannermaa, Arto] Univ Eastern Finland, Pathol & Forens Med, Inst Clin Med, Sch Med, Kuopio, Finland.
[Kosma, Veli-Matti; Mannermaa, Arto] Kuopio Univ Hosp, Dept Clin Pathol, Imaging Ctr, SF-70210 Kuopio, Finland.
[Kriebel, Jennifer] German Ctr Diabet Res, Neuherberg, Germany.
[Kristensen, Vessela] Univ Oslo, Oslo Univ Hosp, Dept Clin Mol Biol, Oslo, Norway.
[Lambrechts, Diether] VIB, Vesalius Res Ctr, Leuven, Belgium.
[Lambrechts, Diether] Univ Leuven, Dept Oncol, Lab Translat Genet, Leuven, Belgium.
[Liu, Yongmei] Wake Forest Sch Med, Div Publ Hlth Sci, Ctr Human Genet, Winston Salem, NC USA.
[Margolin, Sara] Karolinska Inst, Dept Oncology Pathol, Stockholm, Sweden.
[Martin, Nicholas G.; Montgomery, Grant W.] QIMR Berghofer Med Res Inst, Brisbane, Qld, Australia.
[Meindl, Alfons] Tech Univ Munich, Div Obstet & Gynecol, D-80290 Munich, Germany.
[Mueller-Nurasyid, Martina] Univ Munich, Dept Med 1, Munich, Germany.
[Mueller-Nurasyid, Martina] German Ctr Cardiovasc Res DZHK, Partner Site Munich Heart Alliance, Munich, Germany.
[Nalls, Michael] NIA, Neurogenet Lab, Bethesda, MD 20892 USA.
[Nevanlinna, Heli] Univ Helsinki, Dept Obstet & Gynecol, Helsinki, Finland.
[Neven, Patrick] Univ Hosp Leuven, Dept Oncol, Leuven, Belgium.
[Newman, Anne B.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA.
[Newman, Anne B.] Univ Pittsburgh, Dept Med, Pittsburgh, PA USA.
[Newman, Anne B.] Univ Pittsburgh, Dept Clin & Translat Sci, Pittsburgh, PA USA.
[Padmanabhan, Sandosh] Univ Glasgow, British Heart Fdn, Glasgow Cardiovasc Res Ctr, Inst Cardiovasc & Med Sci,Coll Med Vet & Life Sci, Glasgow, Lanark, Scotland.
[Peterlongo, Paolo] Fdn Ist FIRC Oncol Mol IFOM, Milan, Italy.
[Petersmann, Astrid] Univ Med Greifswald, Inst Clin Chem & Lab Med, Greifswald, Germany.
[Psaty, Bruce M.; Reiner, Alex P.] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA.
[Psaty, Bruce M.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA.
[Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA.
[Pylkas, Katri; Winqvist, Robert] Univ Oulu, Dept Clin Chem, Lab Canc Genet & Tumor Biol, Oulu, Finland.
[Pylkas, Katri; Winqvist, Robert] Ctr NordLab, Northern Finland Lab, Lab Canc Genet & Tumor Biol, Oulu, Finland.
[Radice, Paolo] Fdn IRCCS, Ist Nazl Tumori, Dept Prevent & Predict Med, Unit Mol Bases Genet Risk & Genet Testing, Milan, Italy.
[Raffel, Leslie J.] Cedars Sinai Med Ctr, Med Genet Res Ctr, Los Angeles, CA 90048 USA.
[Raffel, Leslie J.] Univ Calif Los Angeles, Cedars Sinai Med Ctr, Clin & Translat Sci Inst, Los Angeles, CA 90048 USA.
[Rudolph, Anja; Chang-Claude, Jenny] German Canc Res Ctr, Div Canc Epidemiol, Heidelberg, Germany.
[Sawyer, Elinor J.] Kings Coll London, Guys Hosp, Res Oncol, London WC2R 2LS, England.
[Schlessinger, David] NIA, Intramural Res Program, Baltimore, MD 21224 USA.
[Schmidt, Marjanka K.] Antoni van Leeuwenhoek Hosp, Netherlands Canc Inst, Amsterdam, Netherlands.
[Schmutzler, Rita K.] Univ Hosp Cologne, Dept Gynecol & Obstet, Div Mol Gynecooncol, Cologne, Germany.
[Schmutzler, Rita K.] Univ Hosp Cologne, Ctr Familial Breast & Ovarian Canc, Cologne, Germany.
[Schmutzler, Rita K.] Univ Hosp Cologne, Ctr Integrated Oncol, Cologne, Germany.
[Simard, Jacques] Univ Laval, Ctr Hosp Univ Quebec, Res Ctr, Quebec City, PQ, Canada.
[Toland, Amanda E.] Univ Melbourne, Dept Pathol, Melbourne, Vic, Australia.
[Strauch, Konstantin] Univ Munich, Inst Med Informat Biometry & Epidemiol, Chair Genet Epidemiol, Munich, Germany.
[Swerdlow, Anthony] Inst Canc Res, Div Breast Canc Res, London SW3 6JB, England.
[Toland, Amanda E.] Ohio State Univ, Ctr Comprehens Canc, Dept Mol Virol Immunol & Med Genet, Columbus, OH 43210 USA.
[Tomlinson, Ian] Churchill Hosp, NIHR Oxford Biomed Res Ctr, Oxford OX3 7LJ, England.
[Tryggvadottir, Laufey] Icelandic Canc Registry, Reykjavik, Iceland.
[Turner, Stephen T.] Mayo Clin, Dept Internal Med, Div Nephrol & Hypertens, Rochester, MN USA.
[Wellons, Melissa] Vanderbilt Univ, Med Ctr, Dept Med, Nashville, TN USA.
[Wolffenbuttel, Bruce B. H. R.] Univ Groningen, Univ Med Ctr Groningen, Dept Endocrinol, Groningen, Netherlands.
[Wolffenbuttel, Bruce B. H. R.] Univ Groningen, Univ Med Ctr Groningen, LifeLines Cohort Study & Biobank, Groningen, Netherlands.
[Yannoukakos, Drakoulis] Natl Ctr Sci Res Demokritos, Inst Radioisotopes & Radiodiagnost Prod, Mol Diagnost Lab, Athens, Greece.
[Zygmunt, Marek] Univ Med Greifswald, Dept Gynecol & Obstet, Greifswald, Germany.
[Alizadeh, Behrooz Z.] Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Groningen, Netherlands.
[Kraft, Peter; Ong, Ken K.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Ong, Ken K.] Univ Cambridge, Dept Paediat, Cambridge, England.
[Murabito, Joanne M.] Boston Univ, Sch Med, Dept Med, Gen Internal Med Sect, Boston, MA 02118 USA.
RP Perry, JRB (reprint author), Univ Cambridge, MRC, Epidemiol Unit, Sch Clin Med,Inst Metab Sci, Cambridge Biomed Campus, Cambridge, England.
EM john.perry@mrc-epid.cam.ac.uk
RI Padmanabhan, Sandosh/S-3963-2016; Brenner, Hermann/B-4627-2017; Polasek,
Ozren/B-6002-2011; Kolcic, Ivana/E-2713-2017; Gudnason,
Vilmundur/K-6885-2015; Smith, Albert Vernon/K-5150-2015; ruggiero,
daniela/K-5638-2016; mangino, massimo/F-5134-2011; Dork,
Thilo/J-8620-2012; Johnson, Andrew/G-6520-2013; Franke,
Lude/P-7036-2016; Schmidt, Frank, ZIK FunGene/B-6075-2009; Knight,
Julia/A-6843-2012; Montgomery, Grant/B-7148-2008; Li,
Jingmei/I-2904-2012; Bielinski, Suzette/A-2238-2009; Bowtell,
David/H-1007-2016; Bruning, Thomas/G-8120-2015; Andrulis,
Irene/E-7267-2013
OI Smith, Jennifer/0000-0002-3575-5468; Ewing, Ailith/0000-0002-2272-1277;
Arndt, Volker/0000-0001-9320-8684; Bergmann, Sven/0000-0002-6785-9034;
Tryggvadottir, Laufey/0000-0001-8067-9030; NUTILE,
TERESA/0000-0001-7062-8352; Dunning, Alison
Margaret/0000-0001-6651-7166; Karasik, David/0000-0002-8826-0530;
Wolffenbuttel, Bruce H.R./0000-0001-9262-6921; dos Santos Silva,
Isabel/0000-0002-6596-8798; vozzi, diego/0000-0002-2902-8184; Cox,
Angela/0000-0002-5138-1099; Girotto, Giorgia/0000-0003-4507-6589;
Chapman, Ross/0000-0002-6477-4254; Yannoukakos,
Drakoulis/0000-0001-7509-3510; Brenner, Hermann/0000-0002-6129-1572;
Polasek, Ozren/0000-0002-5765-1862; Kolcic, Ivana/0000-0001-7918-6052;
Day, Felix/0000-0003-3789-7651; Vuckovic, Dragana/0000-0001-9343-6142;
Magi, Reedik/0000-0002-2964-6011; Schoemaker,
Minouk/0000-0001-8403-2234; Murray, Anna/0000-0002-2351-2522; Hocking,
Lynne J/0000-0002-2414-2826; Gudnason, Vilmundur/0000-0001-5696-0084;
Smith, Albert Vernon/0000-0003-1942-5845; ruggiero,
daniela/0000-0003-3898-7827; mangino, massimo/0000-0002-2167-7470;
Franke, Lude/0000-0002-5159-8802; Montgomery, Grant/0000-0002-4140-8139;
Li, Jingmei/0000-0001-8587-7511; Bielinski, Suzette/0000-0002-2905-5430;
Bowtell, David/0000-0001-9089-7525; Bruning, Thomas/0000-0001-9560-5464;
FU Cancer Research UK [C5047/A15007, 10124, 11174, C12292/A11174,
C1281/A12014, C1287/A 10710, C1287/A10118, C5047/A10692, C5047/A8384,
C8197/A16565]; Chief Scientist Office [CZD/16/6/4]; Medical Research
Council [MC_PC_U127561128, MC_U106179471, MC_U106179472, MC_UU_12015/1,
MC_UU_12015/2]; NCATS NIH HHS [UL1 TR000124, UL1 TR001108, UL1TR000124];
NCI NIH HHS [1U19 CA148065, 1U19 CA148112, 1U19 CA148537, CA128978,
CA164920, P30 CA015704, UM1 CA182910, UM1 CA182913]; NCRR NIH HHS
[UL1RR025005]; NHGRI NIH HHS [HG005552, HG005581, HG006513, HG007022,
HG007089, U01HG004402]; NHLBI NIH HHS [5RC2HL102419, HL043851, HL054457,
HL054464, HL054481, HL080295, HL080467, HL087652, HL087660, HL105756,
K01-HL116770, N01-HC-25195, N01-HC-95159, N01-HC-95160, N01-HC-95161,
N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083,
N01HC85086, N02-HL-6-4278, R01 HL087660, R01 HL119443, R01HL087641,
R01HL59367, U01-HL72515, U01-HL84756]; NIA NIH HHS [1R01AG032098-01A1,
AG009740, AG023629, N.1-AG-1-1, N.1-AG-1-2111, N01-AG-1-2109,
N01-AG-5-0002, N01AG62101, N01AG62103, N01AG62106, R01AG29451,
R21AG032598, RC2 AG036495, RC4 AG039029, U01AG009740]; NIDDK NIH HHS
[DK063491, P30 DK063491, P30 DK072488, P30-DK072488, R01DK075787]; PHS
HHS [HHSN268200625226C, HHSN268200782096C, HHSN268200800007C,
HHSN268200960009C, HHSN268201100001C, HHSN268201100002C,
HHSN268201100003C, HHSN268201100004C, HHSN268201100005C,
HHSN268201100006C, HHSN268201100007C, HHSN268201100008C,
HHSN268201100009C, HHSN268201100010C, HHSN268201100011C,
HHSN268201100012C, HHSN268201100046C, HHSN268201200036C,
HHSN271201100004C, HHSN271201100005C, R01-088119]; Wellcome Trust
[090532]
NR 60
TC 22
Z9 23
U1 4
U2 29
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1061-4036
EI 1546-1718
J9 NAT GENET
JI Nature Genet.
PD NOV
PY 2015
VL 47
IS 11
BP 1294
EP +
DI 10.1038/ng.3412
PG 12
WC Genetics & Heredity
SC Genetics & Heredity
GA CV1BN
UT WOS:000363988200013
PM 26414677
ER
PT J
AU Zoledziewska, M
Sidore, C
Chiang, CWK
Sanna, S
Mulas, A
Steri, M
Busonero, F
Marcus, JH
Marongiu, M
Maschio, A
Del Vecchyo, DO
Floris, M
Meloni, A
Delitala, A
Concas, MP
Murgia, F
Biino, G
Vaccargiu, S
Nagaraja, R
Lohmueller, KE
Timpson, NJ
Soranzo, N
Tachmazidou, I
Dedoussis, G
Zeggini, E
Uzzau, S
Jones, C
Lyons, R
Angius, A
Abecasis, GR
Novembre, J
Schlessinger, D
Cucca, F
AF Zoledziewska, Magdalena
Sidore, Carlo
Chiang, Charleston W. K.
Sanna, Serena
Mulas, Antonella
Steri, Maristella
Busonero, Fabio
Marcus, Joseph H.
Marongiu, Michele
Maschio, Andrea
Del Vecchyo, Diego Ortega
Floris, Matteo
Meloni, Antonella
Delitala, Alessandro
Concas, Maria Pina
Murgia, Federico
Biino, Ginevra
Vaccargiu, Simona
Nagaraja, Ramaiah
Lohmueller, Kirk E.
Timpson, Nicholas J.
Soranzo, Nicole
Tachmazidou, Ioanna
Dedoussis, George
Zeggini, Eleftheria
Uzzau, Sergio
Jones, Chris
Lyons, Robert
Angius, Andrea
Abecasis, Goncalo R.
Novembre, John
Schlessinger, David
Cucca, Francesco
CA UK10K Consortium
Understanding Soc Sci Grp
TI Height-reducing variants and selection for short stature in Sardinia
SO NATURE GENETICS
LA English
DT Article
ID HORMONE RECEPTOR DEFICIENCY; BECKWITH-WIEDEMANN-SYNDROME; LOCI;
ASSOCIATION; ECUADOR; EUROPE; WOMEN
AB We report sequencing-based whole-genome association analyses to evaluate the impact of rare and founder variants on stature in 6,307 individuals on the island of Sardinia. We identify two variants with large effects. One variant, which introduces a stop codon in the GHR gene, is relatively frequent in Sardinia (0.87% versus <0.01% elsewhere) and in the homozygous state causes Laron syndrome involving short stature. We find that this variant reduces height in heterozygotes by an average of 4.2 cm (-0.64 s.d.). The other variant, in the imprinted KCNQ1 gene (minor allele frequency (MAF) = 7.7% in Sardinia versus <1% elsewhere) reduces height by an average of 1.83 cm (-0.31 s.d.) when maternally inherited. Additionally, polygenic scores indicate that known height-decreasing alleles are at systematically higher frequencies in Sardinians than would be expected by genetic drift. The findings are consistent with selection for shorter stature in Sardinia and a suggestive human example of the proposed 'island effect' reducing the size of large mammals.
C1 [Zoledziewska, Magdalena; Sidore, Carlo; Sanna, Serena; Mulas, Antonella; Steri, Maristella; Busonero, Fabio; Marongiu, Michele; Maschio, Andrea; Floris, Matteo; Concas, Maria Pina; Murgia, Federico; Vaccargiu, Simona; Cucca, Francesco] CNR, Ist Ric Genet & Biomed, Cagliari, Italy.
[Sidore, Carlo; Maschio, Andrea; Abecasis, Goncalo R.] Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA.
[Chiang, Charleston W. K.; Lohmueller, Kirk E.] Univ Calif Los Angeles, Dept Ecol & Evolutionary Biol, Los Angeles, CA USA.
[Mulas, Antonella; Floris, Matteo; Uzzau, Sergio; Cucca, Francesco] Univ Sassari, Dipartimento Sci Biomed, I-07100 Sassari, Italy.
[Marcus, Joseph H.; Novembre, John] Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA.
[Maschio, Andrea; Lyons, Robert] Univ Michigan, DNA Sequencing Core, Ann Arbor, MI 48109 USA.
[Del Vecchyo, Diego Ortega] Univ Calif Los Angeles, Bioinformat Interdept Program, Los Angeles, CA USA.
[Floris, Matteo; Jones, Chris; Angius, Andrea] Parco Sci & Tecnol Sardegna, Adv Genom Comp Technol, Ctr Adv Studies Res & Dev Sardinia CRS4, Pula, Italy.
[Meloni, Antonella] Osped Microcitemico, Clin Pediat 2, Cagliari, Italy.
[Delitala, Alessandro] Azienda Osped Univ Sassari, Dept Clin & Expt Med, Sassari, Italy.
[Biino, Ginevra] CNR, Ist Genet Mol, I-27100 Pavia, Italy.
[Nagaraja, Ramaiah; Schlessinger, David] NIA, Genet Lab, NIH, Baltimore, MD 21224 USA.
[Timpson, Nicholas J.] Univ Bristol, MRC, Integrat Epidemiol Unit, Bristol, Avon, England.
[Soranzo, Nicole; Tachmazidou, Ioanna; Zeggini, Eleftheria] Wellcome Trust Sanger Inst, Human Genet, Hinxton, England.
[Soranzo, Nicole] Univ Cambridge, Dept Haematol, Cambridge, England.
[Dedoussis, George] Harokopio Univ, Dept Dietet Nutr, Athens, Greece.
[Uzzau, Sergio] Porto Conte Ric, Tramariglio, Alghero, Italy.
RP Zoledziewska, M (reprint author), CNR, Ist Ric Genet & Biomed, Cagliari, Italy.
EM magdalena.zoledziewska@irgb.cnr.it; schlessingerd@mail.nih.gov;
fcucca@uniss.it
RI Biino, Ginevra/B-5334-2013; Angius, Andrea/P-9549-2015; Fox, Laura
/C-6249-2016; Delitala, Alessandro/L-3194-2016;
OI Biino, Ginevra/0000-0002-9936-946X; Angius, Andrea/0000-0003-2596-6461;
Delitala, Alessandro/0000-0003-1729-8969; McKechanie,
Andrew/0000-0003-4273-9906; Timpson, Nicholas/0000-0002-7141-9189;
Mulas, Antonella/0000-0002-6856-1483; Marongiu,
Michele/0000-0002-7289-9815; Steri, Anna Maristella/0000-0001-5869-3872;
Soranzo, Nicole/0000-0003-1095-3852; Chiang,
Charleston/0000-0002-0668-7865
FU US National Institutes of Health (National Institute on Aging, National
Heart, Lung, and Blood Institute); US National Institutes of Health
(National Human Genome Research Institute); National Human Genome
Research Institute [HG005581, HG005552, HG006513, HG007089, HG007022];
National Heart, Lung, and Blood Institute [HL117626]; Intramural
Research Program of the US National Institutes of Health, National
Institute on Aging [N01-AG-1-2109, HHSN271201100005C]; Sardinian
Autonomous Region [cRP3-154, L.R.7/2009]; grant FaReBio 'Farmaci e Reti
Biotecnologiche di Qualita'; InterOmics MIUR Flagship Project [PB05]; US
National Institutes of Health National Research Service Award (NRSA)
[F32GM106656]; UC MEXUS-CONACYT [213627]; Italian Ministry of Education,
University and Research (MIUR) grant [5571/DSPAR/2002]; Wellcome Trust
[098051, WT091310]; European Research Council [ERC-2011-StG
280559-SEPI]; European Union (European Social Fund (ESF)); Greek
national funds through the Operational Programme 'Education and Lifelong
Learning' of the National Strategic Reference Framework (NSRF) research
funding programme Heracleitus II, Investing in Knowledge Society Through
the European Social Fund; Economic and Social Research Council; UK10K
FX We thank all the volunteers who generously participated in this study
and made this research possible. All participants provided informed
consent, and the studies were approved by local research ethic
committees: Comitato Etico di Azienda Sanitaria Locale 8, Lanusei
(2009/0016600) and Comitato Etico di Azienda Sanitaria Locale 1, Sassari
(2171/CE). This study was funded in part by the US National Institutes
of Health (National Institute on Aging, National Heart, Lung, and Blood
Institute, and National Human Genome Research Institute). This research
was supported by National Human Genome Research Institute grants
HG005581, HG005552, HG006513, HG007089, HG007022 and HG007089; by
National Heart, Lung, and Blood Institute grant HL117626; by the
Intramural Research Program of the US National Institutes of Health,
National Institute on Aging, contracts N01-AG-1-2109 and
HHSN271201100005C; by Sardinian Autonomous Region (L.R.7/2009) grant
cRP3-154; by grant FaReBio2011 'Farmaci e Reti Biotecnologiche di
Qualita'; by the PB05 InterOmics MIUR Flagship Project; by a US National
Institutes of Health National Research Service Award (NRSA) postdoctoral
fellowship (F32GM106656) to C.W.K.C.; by UC MEXUS-CONACYT doctoral
fellowship 213627 to D.O.D.V.; and by Italian Ministry of Education,
University and Research (MIUR) grant 5571/DSPAR/2002. The HELIC study
was funded by the Wellcome Trust (098051) and the European Research
Council (ERC-2011-StG 280559-SEPI). The TEENAGE study has been supported
by the Wellcome Trust (098051), European Union (European Social Fund
(ESF)) and Greek national funds through the Operational Programme
'Education and Lifelong Learning' of the National Strategic Reference
Framework (NSRF) research funding programme Heracleitus II, Investing in
Knowledge Society Through the European Social Fund. The UK Household
Longitudinal Study is led by the Institute for Social and Economic
Research at the University of Essex and funded by the Economic and
Social Research Council. Information on how to access the data can be
found on the Understanding Society website
(https://www.understandingsociety.ac.uk/). This study makes use of data
generated by the UK10K Consortium, derived from samples from
UK10K_COHORTS_TWINSUK (the TwinsUK cohort) and UK10K_COHORT_ALSPAC (the
Avon Longitudinal Study of Parents and Children cohort). A full list of
the investigators who contributed to the generation of the data is
available from http://www.UK10K.org/. Funding for UK10K was provided by
the Wellcome Trust under award WT091310. We thank J. Berg for scripts
and suggestions on the polygenic score analysis.
NR 35
TC 8
Z9 8
U1 1
U2 10
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1061-4036
EI 1546-1718
J9 NAT GENET
JI Nature Genet.
PD NOV
PY 2015
VL 47
IS 11
BP 1352
EP +
DI 10.1038/ng.3403
PG 7
WC Genetics & Heredity
SC Genetics & Heredity
GA CV1BN
UT WOS:000363988200020
PM 26366551
ER
PT J
AU Robinson, MR
Hemani, G
Medina-Gomez, C
Mezzavilla, M
Esko-, T
Shakhbazov, K
Powell, JE
Vinkhuyzen, A
Berndt, SI
Gustafsson, S
Justice, AE
Kahali, B
Locke, AE
Pers, TH
Vedantam, S
Wood, AR
van Rheenen, W
Andreassen, OA
Gasparini, P
Metspalu, A
van den Berg, LH
Veldink, JH
Rivadeneira, F
Werge, TM
Abecasis, GR
Boomsma, DI
Chasman, DI
de Geus, EJC
Frayling, TM
Hirschhorn, JN
Hottenga, JJ
Ingelsson, E
Loos, RJF
Magnusson, PKE
Martin, NG
Montgomery, GW
North, KE
Pedersen, NL
Spector, TD
Speliotes, EK
Goddard, ME
Yang, J
Visscher, PM
AF Robinson, Matthew R.
Hemani, Gibran
Medina-Gomez, Carolina
Mezzavilla, Massimo
Esko-, Tonu
Shakhbazov, Konstantin
Powell, Joseph E.
Vinkhuyzen, Anna
Berndt, Sonja I.
Gustafsson, Stefan
Justice, Anne E.
Kahali, Bratati
Locke, Adam E.
Pers, Tune H.
Vedantam, Sailaja
Wood, Andrew R.
van Rheenen, Wouter
Andreassen, Ole A.
Gasparini, Paolo
Metspalu, Andres
van den Berg, Leonard H.
Veldink, Jan H.
Rivadeneira, Fernando
Werge, Thomas M.
Abecasis, Goncalo R.
Boomsma, Dorret I.
Chasman, Daniel I.
de Geus, Eco J. C.
Frayling, Timothy M.
Hirschhorn, Joel N.
Hottenga, Jouke Jan
Ingelsson, Erik
Loos, Ruth J. F.
Magnusson, Patrik K. E.
Martin, Nicholas G.
Montgomery, Grant W.
North, Kari E.
Pedersen, Nancy L.
Spector, Timothy D.
Speliotes, Elizabeth K.
Goddard, Michael E.
Yang, Jian
Visscher, Peter M.
TI Population genetic differentiation of height and body mass index across
Europe
SO NATURE GENETICS
LA English
DT Article
ID ESTIMATING F-STATISTICS; NATURAL-SELECTION; NONCOMMUNICABLE DISEASES;
SYSTEMATIC ANALYSIS; GLOBAL VARIATION; COMPLEX TRAITS; HUMAN GENOME;
COMMON SNPS; BURDEN; MORTALITY
AB Across-nation differences in the mean values for complex traits are common(1-8), but the reasons for these differences are unknown. Here we find that many independent loci contribute to population genetic differences in height and body mass index (BMI) in 9,416 individuals across 14 European countries. Using discovery data on over 250,000 individuals and unbiased effect size estimates from 17,500 sibling pairs, we estimate that 24% (95% credible interval (CI) = 9%, 41%) and 8% (95% CI = 4%, 16%) of the captured additive genetic variance for height and BMI, respectively, reflect population genetic differences. Population genetic divergence differed significantly from that in a null model (height, P < 3.94 x 10(-8); BMI, P < 5.95 x 10(-4)), and we find an among-population genetic correlation for tall and slender individuals (r = -0.80, 95% CI = -0.95, -0.60), consistent with correlated selection for both phenotypes. Observed differences in height among populations reflected the predicted genetic means (r = 0.51; P < 0.001), but environmental differences across Europe masked genetic differentiation for BMI (P < 0.58).
C1 [Robinson, Matthew R.; Hemani, Gibran; Shakhbazov, Konstantin; Powell, Joseph E.; Vinkhuyzen, Anna; Yang, Jian; Visscher, Peter M.] Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia.
[Medina-Gomez, Carolina; Rivadeneira, Fernando] Erasmus Univ, Dept Internal Med, Med Ctr, Rotterdam, Netherlands.
[Mezzavilla, Massimo; Gasparini, Paolo] Ist Ricovero & Cura Carattere Sci IRCCS, Inst Maternal & Child Hlth, Trieste, Italy.
[Mezzavilla, Massimo] Wellcome Trust Sanger Inst, Hinxton, Cambs, England.
[Esko-, Tonu; Metspalu, Andres; Hirschhorn, Joel N.] Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia.
[Esko-, Tonu; Pers, Tune H.; Vedantam, Sailaja; Hirschhorn, Joel N.] Boston Childrens Hosp, Ctr Basic & Translat Obes Res, Boston, MA USA.
[Esko-, Tonu; Pers, Tune H.; Vedantam, Sailaja; Hirschhorn, Joel N.] Broad Inst MIT & Harvard, Cambridge, MA USA.
[Esko-, Tonu; Pers, Tune H.; Chasman, Daniel I.; Hirschhorn, Joel N.] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA.
[Powell, Joseph E.; Yang, Jian; Visscher, Peter M.] Univ Queensland, Translat Res Inst, Diamantina Inst, Brisbane, Qld, Australia.
[Berndt, Sonja I.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Gustafsson, Stefan] Uppsala Univ, Dept Med Sci, Mol Epidemiol & Sci Life Lab, Uppsala, Sweden.
[Justice, Anne E.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA.
[Kahali, Bratati; North, Kari E.] Univ Michigan, Dept Internal Med, Div Gastroenterol, Ann Arbor, MI 48109 USA.
[Kahali, Bratati; North, Kari E.] Univ Michigan, Dept Computat Med & Bioinformat, Ann Arbor, MI 48109 USA.
[Locke, Adam E.; Abecasis, Goncalo R.; Speliotes, Elizabeth K.] Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48109 USA.
[Pers, Tune H.] Tech Univ Denmark, Dept Syst Biol, Ctr Biol Sequence Anal, DK-2800 Lyngby, Denmark.
[Frayling, Timothy M.] Univ Exeter, Sch Med, Genet Complex Traits, Exeter, Devon, England.
[van Rheenen, Wouter; van den Berg, Leonard H.; Veldink, Jan H.] Univ Med Ctr Utrecht, Brain Ctr Rudolf Magnus, Dept Neurol & Neurosurg, Utrecht, Netherlands.
[Andreassen, Ole A.] Univ Oslo, Oslo Univ Hosp, Norwegian Ctr Mental Disorders Res NORMENT, KG Jebsen Ctr Psychosis Res,Div Mental Hlth & Add, Oslo, Norway.
[Andreassen, Ole A.] Univ Oslo, Inst Clin Med, Oslo, Norway.
[Werge, Thomas M.] Mental Hlth Devices Copenhagen, MHC Sct Hans, Inst Biol Psychiat, Roskilde, Denmark.
[Werge, Thomas M.] Univ Copenhagen, Dept Clin Med, Fac Hlth & Med Sci, Copenhagen, Denmark.
[Werge, Thomas M.] Lundbeck Fdn Initiat Integrat Psychiat Res iPSYCH, Aarhus, Denmark.
[Boomsma, Dorret I.; de Geus, Eco J. C.; Hottenga, Jouke Jan] Vrije Univ Amsterdam Med Ctr, Amsterdam, Netherlands.
[Boomsma, Dorret I.; de Geus, Eco J. C.; Hottenga, Jouke Jan] Vrije Univ Amsterdam Med Ctr, EMGO Inst Hlth & Care Res, Amsterdam, Netherlands.
[Boomsma, Dorret I.; de Geus, Eco J. C.; Hottenga, Jouke Jan] Vrije Univ Amsterdam, Dept Biol Psychol, Amsterdam, Netherlands.
[Chasman, Daniel I.] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA.
[Ingelsson, Erik] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.
[Loos, Ruth J. F.] Univ Cambridge, Addenbrookes Hosp, Inst Metab Sci, MRC,Epidemiol Unit, Cambridge CB2 2QQ, England.
[Loos, Ruth J. F.] Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY 10029 USA.
[Loos, Ruth J. F.] Icahn Sch Med Mt Sinai, Genet Obes & Related Metab Traits Program, New York, NY 10029 USA.
[Loos, Ruth J. F.] Icahn Sch Med Mt Sinai, Mindich Child Hlth & Dev Inst, New York, NY 10029 USA.
[Magnusson, Patrik K. E.; Pedersen, Nancy L.] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
[Martin, Nicholas G.; Montgomery, Grant W.] QIMR Berghofer Med Res Inst, Brisbane, Qld, Australia.
[North, Kari E.] Univ N Carolina, Carolina Ctr Genome Sci, Chapel Hill, NC USA.
[Spector, Timothy D.] Kings Coll London, St Thomas Hosp, Dept Twin Res & Genet Epidemiol, London WC2R 2LS, England.
[Goddard, Michael E.] Dept Primary Ind, Biosci Res Div, Melbourne, Vic, Australia.
[Goddard, Michael E.] Univ Melbourne, Dept Food & Agr Syst, Melbourne, Vic, Australia.
RP Robinson, MR (reprint author), Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia.
EM m.robinson11@uq.edu.au; peter.visscher@uq.edu.au
RI Montgomery, Grant/B-7148-2008; Yang, Jian/A-5852-2010; Magnusson,
Patrik/C-4458-2017;
OI Vinkhuyzen, Anna/0000-0003-3352-0603; Visscher,
Peter/0000-0002-2143-8760; de Geus, Eco/0000-0001-6022-2666; Montgomery,
Grant/0000-0002-4140-8139; Yang, Jian/0000-0003-2001-2474; Mezzavilla,
Massimo/0000-0002-9000-4595; Goddard, Michael/0000-0001-9917-7946;
Locke, Adam/0000-0001-6227-198X; Rivadeneira,
Fernando/0000-0001-9435-9441
FU Australian National Health and Medical Research Council (NHMRC)
[1078037, 1048853, 1050218]; Australian Research Council [DE130100691];
Charles and Sylvia Viertel Senior Medical Research Fellowship; NHMRC
[1052684]; Swedish Research Council [M-2005-1112]; GenomEUtwin
[EU/QLRT-2001-01254, QLG2-CT-2002-01254]; US National Institutes of
Health (NIH) [DK U01-066134]; Swedish Foundation for Strategic Research
(SSF); Heart and Lung Foundation [20070481]; Netherlands Organization
for Scientific Research (NWO; MagW/ZonMW) [904-61-090, 985-10-002,
904-61-193, 480-04-004, 400-05-717, Addiction-31160008,
Middelgroot-11-09-032, Spinozapremie 56-464-14192]; Center for Medical
Systems Biology (CSMB; NWO Genomics); NBIC/BioAssist/RK [2008.024];
Biobanking and Biomolecular Resources Research Infrastructure (BBMRI-NL)
[184.021.007]; VU University's Institute for Health and Care Research
(EMGO+); Neuroscience Campus Amsterdam (NCA); European Science
Foundation (ESF) [EU/QLRT-2001-01254]; European Community
[HEALTH-F4-2007-201413]; European Research Council (ERC) [230374];
Rutgers University Cell and DNA Repository (National Institute for
Mental Health (NIMH)) [U24-MH068457-06]; Avera Institute (Sioux Falls,
South Dakota, USA); US NIH [R01-D0042157-01A, 1RC2-MH089951-01,
1RC2-MH089995-01, AA07535, AA10248, AA014041, AA13320, AA13321, AA13326,
DA12854]; Genetic Association Information Network (GAIN) of the
Foundation for the National Institutes of Health; Wellcome Trust; UK
Department of Health via the National Institute for Health Research
(NIHR) comprehensive Biomedical Research Centre award; King's College
London; National Eye Institute via a US NIH/Center for Inherited Disease
Research (CIDR); National Heart, Lung, and Blood Institute (NHLBI);
Boston University [N01-HC-25195]; NHLBI [N02-HL-64278]; Illumina;
Australian NHMRC [241944, 389875, 389891, 389892, 389938, 442915,
442981, 496739, 496688, 552485]; Health Research Board, Ireland;
National Institute on Aging (NIA) [U01-AG09740]; ALS Foundation
Netherlands
FX We thank the reviewers for their very helpful and insightful comments
that greatly improved the manuscript. We also thank B. Hill and O.
Ovaskainen for useful discussions. The University of Queensland group is
supported by the Australian National Health and Medical Research Council
(NHMRC; grants 1078037, 1048853 and 1050218). J.E.P. is supported by
Australian Research Council grant DE130100691. J.Y. is supported by a
Charles and Sylvia Viertel Senior Medical Research Fellowship and by
NHMRC grant 1052684. We thank our colleagues at the Centre for
Neurogenetics and Statistical Genomics for comments and suggestions. We
are grateful to the twins and their families for their generous
participation in the full-sibling family data set, which includes data
from many cohorts and received support from many funding bodies.
TWINGENE was supported by the Swedish Research Council (M-2005-1112),
GenomEUtwin (EU/QLRT-2001-01254 and QLG2-CT-2002-01254), US National
Institutes of Health (NIH) grant DK U01-066134, the Swedish Foundation
for Strategic Research (SSF), and the Heart and Lung Foundation
(20070481). For the Netherlands Twin Register (NTR), funding was
obtained from the Netherlands Organization for Scientific Research (NWO;
MagW/ZonMW grants 904-61-090, 985-10-002, 904-61-193, 480-04-004,
400-05-717, Addiction-31160008, Middelgroot-11-09-032 and Spinozapremie
56-464-14192), the Center for Medical Systems Biology (CSMB; NWO
Genomics), NBIC/BioAssist/RK(2008.024), Biobanking and Biomolecular
Resources Research Infrastructure (BBMRI-NL; 184.021.007), the VU
University's Institute for Health and Care Research (EMGO+) and
Neuroscience Campus Amsterdam (NCA), the European Science Foundation
(ESF; EU/QLRT-2001-01254), the European Community's Seventh Framework
Programme (FP7/2007-2013) under the ENGAGE project grant agreement
(HEALTH-F4-2007-201413), the European Research Council (ERC Advanced;
230374), the Rutgers University Cell and DNA Repository (National
Institute for Mental Health (NIMH), U24-MH068457-06), the Avera
Institute (Sioux Falls, South Dakota, USA) and the US NIH
(R01-D0042157-01A, Grand Opportunity grants 1RC2-MH089951-01 and
1RC2-MH089995-01). Part of the genotyping and analyses were funded by
the Genetic Association Information Network (GAIN) of the Foundation for
the National Institutes of Health. The TwinsUK study was funded by the
Wellcome Trust and the European Community's Seventh Framework Programme
(FP7/2007-2013) under the ENGAGE project grant agreement
(HEALTH-F4-2007-201413). TwinsUK also receives support from the UK
Department of Health via the National Institute for Health Research
(NIHR) comprehensive Biomedical Research Centre award to Guy's and St
Thomas' National Health Service (NHS) Foundation Trust in partnership
with King's College London. T.D.S. is the holder of an ERC Advanced
Principal Investigator award. Genotyping for the TwinsUK study was
performed by the Wellcome Trust Sanger Institute, with the support of
the National Eye Institute via a US NIH/Center for Inherited Disease
Research (CIDR) genotyping project. The Framingham Heart Study is
conducted and supported by the National Heart, Lung, and Blood Institute
(NHLBI) in collaboration with Boston University (contract N01-HC-25195).
This manuscript was not prepared in collaboration with investigators of
the Framingham Heart Study and does not necessarily reflect the opinions
or views of the Framingham Heart Study, Boston University or NHLBI.
Funding for SHARe Affymetrix genotyping was provided by NHLBI contract
N02-HL-64278.; Funding for SHARe Illumina genotyping was provided under
an agreement between Illumina and Boston University. The QIMR
researchers acknowledge funding from the Australian NHMRC (grants
241944, 389875, 389891, 389892, 389938, 442915, 442981, 496739, 496688
and 552485) and the US NIH (grants AA07535, AA10248, AA014041, AA13320,
AA13321, AA13326 and DA12854). We are grateful to M. Gill (Trinity
College Dublin) and K. Nicodemus (University of Edinburgh) for access to
the ISC-Trinity College Dublin cohort, which was supported by the
Wellcome Trust and the Health Research Board, Ireland. Access to the
Bulgarian cohort data was kindly facilitated by G. Kirov and V.
Excott-Price. For the Danish cohort, the Danish Scientific Committees
and the Danish Data Protection Agency approved the study and all the
patients gave written informed consent before inclusion in the project.
The National Institute on Aging (NIA) provided funding for the Health
and Retirement Study (HRS; U01-AG09740). The HRS is performed at the
Institute for Social Research at the University of Michigan. This
manuscript was not prepared in collaboration with investigators of the
HRS and does not necessarily reflect the opinions or views of the HRS,
University of Michigan or NIA. The Netherlands genotype samples were
part of Project MinE, which was supported by the ALS Foundation
Netherlands. Research leading to these results has received funding from
the European Community's Seventh Framework Programme (FP7/2007-2013).
NR 58
TC 13
Z9 13
U1 8
U2 30
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1061-4036
EI 1546-1718
J9 NAT GENET
JI Nature Genet.
PD NOV
PY 2015
VL 47
IS 11
BP 1357
EP +
DI 10.1038/ng.3401
PG 8
WC Genetics & Heredity
SC Genetics & Heredity
GA CV1BN
UT WOS:000363988200021
PM 26366552
ER
PT J
AU Yang, W
Lee, YS
AF Yang, Wei
Lee, Young-Sam
TI A DNA-hairpin model for repeat-addition processivity in telomere
synthesis
SO NATURE STRUCTURAL & MOLECULAR BIOLOGY
LA English
DT Editorial Material
ID CATALYTIC SUBUNIT TERT; TETRAHYMENA TELOMERASE; REVERSE-TRANSCRIPTASE;
STRUCTURAL BASIS; RNA; TEMPLATE; FIDELITY; SEQUENCE; BINDING
AB We propose a DNA-hairpin model for the processivity of telomeric-repeat addition. Concomitantly with template-RNA translocation after each repeat synthesis, the complementary DNA repeat, for example, AGGGTT, loops out in a noncanonical base-paired hairpin, thus freeing the RNA template for the next round of repeat synthesis. The DNA hairpin is temporarily stabilized by telomerase and the incoming dGTP but becomes realigned for processive telomere synthesis.
C1 [Yang, Wei] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
[Lee, Young-Sam] Samsung Adv Inst Technol, Well Aging Res Ctr, Suwon, South Korea.
RP Yang, W (reprint author), NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
EM wei.yang@nih.gov
FU Intramural NIH HHS; NIDDK NIH HHS [DK036146-08]
NR 35
TC 2
Z9 2
U1 1
U2 6
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1545-9993
EI 1545-9985
J9 NAT STRUCT MOL BIOL
JI Nat. Struct. Mol. Biol.
PD NOV
PY 2015
VL 22
IS 11
BP 844
EP 847
PG 4
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA CV4ZA
UT WOS:000364273800005
PM 26581517
ER
PT J
AU Freudenthal, BD
Beard, WA
Cuneo, MJ
Dyrkheeva, NS
Wilson, SH
AF Freudenthal, Bret D.
Beard, William A.
Cuneo, Matthew J.
Dyrkheeva, Nadezhda S.
Wilson, Samuel H.
TI Capturing snapshots of APE1 processing DNA damage
SO NATURE STRUCTURAL & MOLECULAR BIOLOGY
LA English
DT Article
ID HUMAN APURINIC/APYRIMIDINIC ENDONUCLEASE; BASE EXCISION-REPAIR; HUMAN
ABASIC ENDONUCLEASE; DOUBLE-STRANDED DNA; METAL-BINDING SITE; INCISION
ACTIVITY; CATALYTIC MECHANISM; PHOSPHODIESTER-BOND; POLYMERASE-BETA; CPG
ISLANDS
AB DNA apurinic-apyrimidinic (AP) sites are prevalent noncoding threats to genomic stability and are processed by AP endonuclease 1 (APE1). APE1 incises the AP-site phosphodiester backbone, generating a DNA-repair intermediate that is potentially cytotoxic. The molecular events of the incision reaction remain elusive, owing in part to limited structural information. We report multiple high-resolution human APE1-DNA structures that divulge new features of the APE1 reaction, including the metal-binding site, the nucleophile and the arginine clamps that mediate product release. We also report APE1-DNA structures with a T-G mismatch 5' to the AP site, representing a clustered lesion occurring in methylated CpG dinucleotides. These structures reveal that APE1 molds the T-G mismatch into a unique Watson-Crick-like geometry that distorts the active site, thus reducing incision. These snapshots provide mechanistic clarity for APE1 while affording a rational framework to manipulate biological responses to DNA damage.
C1 [Freudenthal, Bret D.; Beard, William A.; Dyrkheeva, Nadezhda S.; Wilson, Samuel H.] NIEHS, Genome Integr & Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA.
[Cuneo, Matthew J.] Oak Ridge Natl Lab, Neutron Sci Directorate, Oak Ridge, TN 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
OI Cuneo, Matthew/0000-0002-1475-6656
FU US National Institutes of Health, National Institute of Environmental
Health Sciences [Z01-ES050158, Z01-ES050161]; United States Department
of Energy, Office of Basic Energy Sciences; Eli Lilly and Co.; United
States Department of State, as part of the United States-Russia
Collaboration in the Biomedical Sciences US National Institutes of
Health Visiting Fellows Program
FX We thank the Collaborative Crystallography group at NIEHS for help with
data collection and analysis. We thank L. Pedersen and L. Perera for
valuable discussions. This research was supported in part by the
Intramural Research Program of the US National Institutes of Health,
National Institute of Environmental Health Sciences (project numbers
Z01-ES050158 and Z01-ES050161 (S.H.W.)). A part of this research was
performed at Oak Ridge National Laboratory's Spallation Neutron Source
and the Joint Institute for Neutron Sciences Biophysical
Characterization Laboratory, sponsored by the United States Department
of Energy, Office of Basic Energy Sciences (M.J.C.). N.S.D is supported
in part by Eli Lilly and Co. and the United States Department of State,
as part of the United States-Russia Collaboration in the Biomedical
Sciences US National Institutes of Health Visiting Fellows Program.
NR 57
TC 12
Z9 13
U1 4
U2 13
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1545-9993
EI 1545-9985
J9 NAT STRUCT MOL BIOL
JI Nat. Struct. Mol. Biol.
PD NOV
PY 2015
VL 22
IS 11
BP 924
EP 931
DI 10.1038/nsmb.3105
PG 8
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA CV4ZA
UT WOS:000364273800017
PM 26458045
ER
PT J
AU Miyabe, I
Mizuno, K
Keszthelyi, A
Daigaku, Y
Skouteri, M
Mohebi, S
Kunkel, TA
Murray, JM
Carr, AM
AF Miyabe, Izumi
Mizuno, Ken'Ichi
Keszthelyi, Andrea
Daigaku, Yasukazu
Skouteri, Meliti
Mohebi, Saed
Kunkel, Thomas A.
Murray, Johanne M.
Carr, Antony M.
TI Polymerase delta replicates both strands after homologous
recombination-dependent fork restart
SO NATURE STRUCTURAL & MOLECULAR BIOLOGY
LA English
DT Article
ID BREAK-INDUCED REPLICATION; GROSS CHROMOSOMAL REARRANGEMENTS;
ONCOGENE-INDUCED SENESCENCE; CONSERVATIVE DNA-SYNTHESIS; GENOME
INSTABILITY; TEMPLATE EXCHANGE; INVERTED REPEATS; DAMAGE RESPONSE; CNV
FORMATION; HUMAN-CELLS
AB To maintain genetic stability, DNA must be replicated only once per cell cycle, and replication must be completed even when individual replication forks are inactivated. Because fork inactivation is common, passive convergence of an adjacent fork is insufficient to rescue all inactive forks. Thus, eukaryotic cells have evolved homologous recombination-dependent mechanisms to restart persistent inactive forks. Completing DNA synthesis via homologous recombination-restarted replication (HoRReR) ensures cell survival, but at a cost. One such cost is increased mutagenesis because HoRReR is more error prone than canonical replication. This increased error rate implies the HoRReR mechanism is distinct from that of a canonical fork. Here we demonstrate, in Schizosaccharomyces pombe, that a DNA sequence duplicated by HoRReR during S phase is replicated semiconservatively, but both the leading and lagging strands are synthesized by DNA polymerase delta.
C1 [Miyabe, Izumi; Mizuno, Ken'Ichi; Keszthelyi, Andrea; Skouteri, Meliti; Mohebi, Saed; Murray, Johanne M.; Carr, Antony M.] Univ Sussex, Genome Damage & Stabil Ctr, Brighton, E Sussex, England.
[Daigaku, Yasukazu] Tohoku Univ, Frontier Res Inst Interdisciplinary Sci, Sendai, Miyagi 980, Japan.
[Kunkel, Thomas A.] NIEHS, Genome Integr & Struct Biol Lab, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
RP Carr, AM (reprint author), Univ Sussex, Genome Damage & Stabil Ctr, Brighton, E Sussex, England.
EM a.m.carr@sussex.ac.uk
RI Mizuno, Ken'Ichi/P-7350-2015
OI Mizuno, Ken'Ichi/0000-0001-8115-7808
FU Division of Intramural Research of the US National Institutes of Health
[Z01 ES065070]; Medical Research Council (UK) [G0801078, G1100074];
European Research Council [268788-SMI-DDR]
FX This work was supported by Project Z01 ES065070 (T.A.K.) from the
Division of Intramural Research of the US National Institutes of Health,
by Medical Research Council (UK) grants G0801078 and G1100074 (A.M.C.)
and by European Research Council grant 268788-SMI-DDR (A.M.C.). We thank
H. Masukata (Osaka University) for the cdc20::hphMX6-Pnmtl-cdc2OCTD
strain.
NR 53
TC 7
Z9 7
U1 2
U2 11
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1545-9993
EI 1545-9985
J9 NAT STRUCT MOL BIOL
JI Nat. Struct. Mol. Biol.
PD NOV
PY 2015
VL 22
IS 11
BP 932
EP 938
DI 10.1038/nsmb.3100
PG 7
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA CV4ZA
UT WOS:000364273800018
PM 26436826
ER
PT J
AU Findling, RL
Robb, A
McNamara, NK
Pavuluri, MN
Kafantaris, V
Scheffer, R
Frazier, JA
Rynn, M
DelBello, M
Kowatch, RA
Rowles, BM
Lingler, J
Martz, K
Anand, R
Clemons, TE
Taylor-Zapata, P
AF Findling, Robert L.
Robb, Adelaide
McNamara, Nora K.
Pavuluri, Mani N.
Kafantaris, Vivian
Scheffer, Russell
Frazier, Jean A.
Rynn, Moira
DelBello, Melissa
Kowatch, Robert A.
Rowles, Brieana M.
Lingler, Jacqui
Martz, Karen
Anand, Ravinder
Clemons, Traci E.
Taylor-Zapata, Perdita
TI Lithium in the Acute Treatment of Bipolar I Disorder: A Double-Blind,
Placebo-Controlled Study
SO PEDIATRICS
LA English
DT Article
ID DEPRESSION RATING-SCALE; SUICIDE ATTEMPTS; CONTROLLED-TRIAL;
ADOLESCENTS; CHILDREN; MANIA; RELIABILITY; VALIDITY; YOUTH; METAANALYSIS
AB BACKGROUND: Lithium is a benchmark treatment for bipolar disorder in adults. Definitive studies of lithium in pediatric bipolar I disorder (BP-I) are lacking.
METHODS: This multicenter, randomized, double-blind, placebo-controlled study of pediatric participants (ages 7-17 years) with BP-I/manic or mixed episodes compared lithium (n = 53) versus placebo (n = 28) for up to 8 weeks. The a priori primary efficacy measure was change from baseline to the end of study (week 8/ET) in the Young Mania Rating Scale (YMRS) score, based on last-observation-carried-forward analysis.
RESULTS: The change in YMRS score was significantly larger in lithium-treated participants (5.51 [95% confidence interval: 0.51 to 10.50]) after adjustment for baseline YMRS score, age group, weight group, gender, and study site (P = .03). Overall Clinical Global Impression-Improvement scores favored lithium (n = 25; 47% very much/much improved) compared with placebo (n = 6; 21% very much/much improved) at week 8/ET (P = .03). A statistically significant increase in thyrotropin concentration was seen with lithium (3.0 +/- 3.1 mIU/L) compared with placebo (-0.1 +/- 0.9 mIU/L; P < .001). There was no statistically significant between-group difference with respect to weight gain.
CONCLUSIONS: Lithium was superior to placebo in reducing manic symptoms in pediatric patients treated for BP-I in this clinical trial. Lithium was generally well tolerated in this patient population and was not associated with weight gain, distinguishing it from other agents commonly used to treat youth with bipolar disorder.
C1 [Findling, Robert L.] Johns Hopkins Univ, Kennedy Krieger Inst, Baltimore, MD 21287 USA.
[Robb, Adelaide] George Washington Univ, Childrens Natl Med Ctr, Washington, DC USA.
[McNamara, Nora K.; Lingler, Jacqui] Case Western Reserve Univ, Dept Psychiat, Cleveland, OH 44106 USA.
[Pavuluri, Mani N.] Univ Illinois, Dept Psychiat, Chicago, IL 60612 USA.
[Kafantaris, Vivian] Zucker Hillside Hosp, Manhasset, NY USA.
[Kafantaris, Vivian] North Shore Long Isl Jewish Hlth Syst, Feinstein Inst Med Res, Manhasset, NY USA.
[Scheffer, Russell] Univ Kansas, Sch Med, Wichita, KS 67214 USA.
[Frazier, Jean A.] Univ Massachusetts, Sch Med, UMASS Mem Med Ctr, Dept Psychiat, Worcester, MA USA.
[Rynn, Moira] Columbia Univ, New York State Psychiat Inst, New York, NY USA.
[DelBello, Melissa] Univ Cincinnati, Coll Med, Cincinnati, OH USA.
[Kowatch, Robert A.] Ohio State Univ, Nationwide Childrens Hosp, Wexner Med Ctr, Columbus, OH 43210 USA.
[Rowles, Brieana M.] UPMC CancerCtr, Pittsburgh, PA USA.
[Martz, Karen; Anand, Ravinder; Clemons, Traci E.] EMMES Corp, Rockville, MD USA.
[Taylor-Zapata, Perdita] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
RP Findling, RL (reprint author), Johns Hopkins Univ, 1800 Orleans St,Suite 12344A, Baltimore, MD 21287 USA.
EM rfindli1@jhmi.edu
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development [HHSN275200503406C]; National Institutes of Health (NIH)
FX This work was sponsored by the Eunice Kennedy Shriver National Institute
of Child Health and Human Development, "Best Pharmaceuticals for
Children Act Pediatric Off-Patent Drug Study (PODS): Lithium in the
Treatment of Pediatric Mania" (contract HHSN275200503406C). Funded by
the National Institutes of Health (NIH).
NR 33
TC 7
Z9 7
U1 8
U2 13
PU AMER ACAD PEDIATRICS
PI ELK GROVE VILLAGE
PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA
SN 0031-4005
EI 1098-4275
J9 PEDIATRICS
JI Pediatrics
PD NOV
PY 2015
VL 136
IS 5
BP 885
EP 894
DI 10.1542/peds.2015-0743
PG 10
WC Pediatrics
SC Pediatrics
GA CV0US
UT WOS:000363969600053
PM 26459650
ER
PT J
AU Nesin, M
Sparer, O
AF Nesin, Mirjana
Sparer, Olivia
TI Vaccine monitoring systems: A potential model for medications in
pregnancy
SO SEMINARS IN PERINATOLOGY
LA English
DT Review
DE Vaccine safety monitoring; Maternal immunizations; Medications in
pregnancy
ID SAFETY; IMMUNIZATION; PROGRAM; MOTHERS
AB Multiple vaccine safety systems contribute to monitor and assess the safety of vaccines given to pregnant women and their offspring. This article presents a review of the strengths and limitations of several national vaccine safety systems. The review concludes that the present framework of vaccine safety systems offers lessons to be learned toward the design of a system for monitoring and assessing the safety of medications administered to pregnant women in clinical practice and research. Published by Elsevier Inc.
C1 [Nesin, Mirjana; Sparer, Olivia] NIAID, Div Microbiol & Infect Dis, NIH, Bethesda, MD 20892 USA.
RP Nesin, M (reprint author), NIAID, Div Microbiol & Infect Dis, NIH, 5601 Fishers Lane,MSC 9806, Bethesda, MD 20892 USA.
EM nesinm@niaid.nih.gov
NR 7
TC 0
Z9 0
U1 0
U2 0
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0146-0005
EI 1558-075X
J9 SEMIN PERINATOL
JI Semin. Perinatol.
PD NOV
PY 2015
VL 39
IS 7
BP 524
EP 529
DI 10.1053/j.semperi.2015.08.005
PG 6
WC Obstetrics & Gynecology; Pediatrics
SC Obstetrics & Gynecology; Pediatrics
GA CV4VY
UT WOS:000364265800005
PM 26433628
ER
PT J
AU Ren, ZX
Zajicek, A
AF Ren, Zhaoxia
Zajicek, Anne
TI Review of the Best Pharmaceuticals for Children Act and the Pediatric
Research Equity Act: What can the obstetric community learn from the
pediatric experience?
SO SEMINARS IN PERINATOLOGY
LA English
DT Review
DE Pediatrics; Medications; Pharmacology; Clinical trials; Obstetrics;
Labeling; FDA; Safety; Efficacy; Pharmacokinetics; Outcome measures
AB Children have been called therapeutic orphans as they have been excluded from drug research and new drug development resulting in the lack of proper labels for majority of the drugs for pediatric use. The Best Pharmaceuticals for Children Act (BPCA) and the Pediatric Research Equity Act (PREA) are two legislative mandates to improve pediatric drug labeling. The BPCA legislation authorizes the National Institutes of Health (NIH) to implement research programs through funding clinical trials to study off-patent drugs in pediatric population. Obstetric pharmacology research gaps are in many ways similar to those in pediatrics, including off-label use of common medications, and lack of knowledge of appropriate dosing, safety, and efficacy of drugs. Much research is needed to define mechanisms of disease and drug actions in pregnant women to fill the knowledge gaps. Published by Elsevier Inc.
C1 [Ren, Zhaoxia; Zajicek, Anne] NICHHD, Obstet & Pediat Pharmacol & Therapeut Branch, NIH, Bethesda, MD 20892 USA.
RP Zajicek, A (reprint author), NICHHD, Obstet & Pediat Pharmacol & Therapeut Branch, NIH, 6100 Execut Blvd,Suite 4A01,MSC 7510, Bethesda, MD 20892 USA.
EM zajiceka@mail.nih.gov
FU Intramural NIH HHS [Z99 HD999999]
NR 4
TC 2
Z9 2
U1 1
U2 5
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0146-0005
EI 1558-075X
J9 SEMIN PERINATOL
JI Semin. Perinatol.
PD NOV
PY 2015
VL 39
IS 7
BP 530
EP 531
DI 10.1053/j.semperi.2015.08.006
PG 2
WC Obstetrics & Gynecology; Pediatrics
SC Obstetrics & Gynecology; Pediatrics
GA CV4VY
UT WOS:000364265800006
PM 26455383
ER
PT J
AU White, A
AF White, Amina
TI Accelerating the paradigm shift toward inclusion of pregnant women in
drug research: Ethical and regulatory considerations
SO SEMINARS IN PERINATOLOGY
LA English
DT Review
ID CLINICAL-RESEARCH; TRIALS; RISK
AB Although there has been long-standing reluctance to include pregnant women as clinical trial participants, increasing recognition of profound gaps in research on the safety and efficacy of drugs often prescribed to pregnant women calls into question the practice of routinely excluding them. This article presents compelling reasons for including pregnant women in clinical research, highlights certain regulatory barriers to the inclusion of pregnant women, and proposes that professional societies with expertise in obstetrics and maternal-fetal medicine can be instrumental in hastening the paradigm shift from the systematic exclusion of pregnant women in research to a one of responsible and fair inclusion. Published by Elsevier Inc.
C1 NIH, Dept Bioeth, Ctr Clin, Bethesda, MD 20892 USA.
RP White, A (reprint author), NIH, Dept Bioeth, Ctr Clin, 10 Ctr Dr,1C118, Bethesda, MD 20892 USA.
EM Amina.white@nih.gov
NR 23
TC 0
Z9 0
U1 0
U2 0
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0146-0005
EI 1558-075X
J9 SEMIN PERINATOL
JI Semin. Perinatol.
PD NOV
PY 2015
VL 39
IS 7
BP 537
EP 540
DI 10.1053/j.semperi.2015.08.008
PG 4
WC Obstetrics & Gynecology; Pediatrics
SC Obstetrics & Gynecology; Pediatrics
GA CV4VY
UT WOS:000364265800008
PM 26385413
ER
PT J
AU Nguyen, NL
Powers, KA
Hughes, JP
MacPhail, CL
Piwowar-Manning, E
Patel, EU
Gomez-Olive, FX
Kahn, K
Pettifor, AE
AF Nguyen, Nadia L.
Powers, Kimberly A.
Hughes, James P.
MacPhail, Catherine L.
Piwowar-Manning, Estelle
Patel, Eshan U.
Gomez-Olive, F. Xavier
Kahn, Kathleen
Pettifor, Audrey E.
TI Sexual Partnership Patterns Among South African Adolescent Girls
Enrolled in STI Preventions Trial Network 068: Measurement Challenges
and Implications for HIV/STI Transmission
SO SEXUALLY TRANSMITTED DISEASES
LA English
DT Article
ID SUB-SAHARAN AFRICA; CONCURRENT PARTNERSHIPS; HIV EPIDEMICS; ROSENTHAL;
LURIE; GAPS; DYNAMICS; LENGTHS; DISEASE; HEALTH
AB Background Estimates of sexual partnership durations, gaps between partnerships, and overlaps across partnerships are important for understanding sexual partnership patterns and developing interventions to prevent transmission of HIV/sexually transmitted infections (STIs). However, a validated, optimal approach for estimating these parameters, particularly when partnerships are ongoing, has not been established.
Methods We assessed 4 approaches for estimating partnership parameters using cross-sectional reports on dates of first and most recent sex and partnership status (ongoing or not) from 654 adolescent girls in rural South Africa. The first, commonly used, approach assumes all partnerships have ended, resulting in underestimated durations for ongoing partnerships. The second approach treats reportedly ongoing partnerships as right-censored, resulting in bias if partnership status is reported with error. We propose 2 hybrid approaches, which assign partnership status to reportedly ongoing partnerships based on how recently girls last had sex with their partner. We estimate partnership duration, gap length, and overlap length under each approach using Kaplan-Meier methods with a robust variance estimator.
Results Median partnership duration and overlap length varied considerably across approaches (from 368 to 1024 days and 168 to 409 days, respectively), but gap length was stable. Lifetime prevalence of concurrency ranged from 28% to 33%, and at least half of gap lengths were shorter than 6 months, suggesting considerable potential for HIV/STI transmission.
Conclusions Estimates of partnership duration and overlap lengths are highly dependent on measurement approach. Understanding the effect of different approaches on estimates is critical for interpreting partnership data and using estimates to predict HIV/STI transmission rates.
C1 [Nguyen, Nadia L.; Powers, Kimberly A.; Pettifor, Audrey E.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA.
[Hughes, James P.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[MacPhail, Catherine L.] Univ New England, Armidale, NSW, Australia.
[Piwowar-Manning, Estelle] Johns Hopkins Univ, Dept Pathol, Baltimore, MD USA.
[Patel, Eshan U.] NIH, Bethesda, MD 20892 USA.
[Gomez-Olive, F. Xavier; Kahn, Kathleen] Agincourt, MRC Wits Rural Publ Hlth & Hlth Transit Res Unit, Johannesburg, South Africa.
RP Nguyen, NL (reprint author), 135 Dauer Dr,2101 McGavran Greenberg Hall, Chapel Hill, NC 27599 USA.
EM nadia.nguyen@unc.edu
OI Patel, Eshan/0000-0003-2174-5004
FU National Institutes of Health [T32 AI007001, KL2 TR001109]; National
Institute of Mental Health [R01 MH087118, UM1 AI068619, UM1 AI068617,
UM1 AI068613]; Division of Intramural Research, National Institute of
Allergy and Infectious Diseases; National Institute of Allergy and
Infectious Diseases; National Institute on Drug Abuse
FX Financial support: This work was supported by the National Institutes of
Health (T32 AI007001, KL2 TR001109), the National Institute of Mental
Health (R01 MH087118), and the Division of Intramural Research, the
National Institute of Allergy and Infectious Diseases. Additional
support was provided, in part, by the National Institute of Allergy and
Infectious Diseases, the National Institute on Drug Abuse, and the
National Institute of Mental Health through Cooperative Agreements (UM1
AI068619, UM1 AI068617, and UM1 AI068613).
NR 31
TC 1
Z9 1
U1 2
U2 7
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0148-5717
EI 1537-4521
J9 SEX TRANSM DIS
JI Sex. Transm. Dis.
PD NOV
PY 2015
VL 42
IS 11
BP 612
EP 618
DI 10.1097/OLQ.0000000000000357
PG 7
WC Infectious Diseases
SC Infectious Diseases
GA CV2LY
UT WOS:000364089400003
PM 26462185
ER
PT J
AU Hofer, E
Cavalieri, M
Bis, JC
DeCarli, C
Fornage, M
Sigurdsson, S
Srikanth, V
Trompet, S
Verhaaren, BFJ
Wolf, C
Yang, Q
Adams, HHH
Amouyel, P
Beiser, A
Buckley, BM
Callisaya, M
Chauhan, G
de Craen, AJM
Dufouil, C
van Duijn, CM
Ford, I
Freudenberger, P
Gottesman, RF
Gudnason, V
Heiss, G
Hofman, A
Lumley, T
Martinez, O
Mazoyer, B
Moran, C
Niessen, WJ
Phan, T
Psaty, BM
Satizabal, CL
Sattar, N
Schilling, S
Shibata, DK
Slagboom, PE
Smith, A
Stott, DJ
Taylor, KD
Thomson, R
Toglhofer, AM
Tzourio, C
van Buchem, M
Wang, J
Westendorp, RGJ
Windham, BG
Vernooij, MW
Zijdenbos, A
Beare, R
Debette, S
Ikram, MA
Jukema, JW
Launer, LJ
Longstreth, WT
Mosley, TH
Seshadri, S
Schmidt, H
Schmidt, R
AF Hofer, Edith
Cavalieri, Margherita
Bis, Joshua C.
DeCarli, Charles
Fornage, Myriam
Sigurdsson, Sigurdur
Srikanth, Velandai
Trompet, Stella
Verhaaren, Benjamin F. J.
Wolf, Christiane
Yang, Qiong
Adams, Hieab H. H.
Amouyel, Philippe
Beiser, Alexa
Buckley, Brendan M.
Callisaya, Michele
Chauhan, Ganesh
de Craen, Anton J. M.
Dufouil, Carole
van Duijn, Cornelia M.
Ford, Ian
Freudenberger, Paul
Gottesman, Rebecca F.
Gudnason, Vilmundur
Heiss, Gerardo
Hofman, Albert
Lumley, Thomas
Martinez, Oliver
Mazoyer, Bernard
Moran, Chris
Niessen, Wiro J.
Thanh Phan
Psaty, Bruce M.
Satizabal, Claudia L.
Sattar, Naveed
Schilling, Sabrina
Shibata, Dean K.
Slagboom, P. Eline
Smith, Albert
Stott, David J.
Taylor, Kent D.
Thomson, Russell
Toeglhofer, Anna M.
Tzourio, Christophe
van Buchem, Mark
Wang, Jing
Westendorp, Rudi G. J.
Windham, B. Gwen
Vernooij, Meike W.
Zijdenbos, Alex
Beare, Richard
Debette, Stephanie
Ikram, M. Arfan
Jukema, J. Wouter
Launer, Lenore J.
Longstreth, W. T., Jr.
Mosley, Thomas H.
Seshadri, Sudha
Schmidt, Helena
Schmidt, Reinhold
CA Cohorts Heart Aging Res Genomic Ep
TI White Matter Lesion Progression Genome-Wide Search for Genetic
Influences
SO STROKE
LA English
DT Article
ID SMALL-VESSEL DISEASE; RENIN-ANGIOTENSIN SYSTEM; CEREBROVASCULAR
RISK-FACTORS; AUSTRIAN STROKE PREVENTION; ANALYSIS IDENTIFIES 13;
ELDERLY MALE TWINS; BLOOD-PRESSURE; HYPERINTENSITY VOLUME; CAROTID
ATHEROSCLEROSIS; FUNCTIONAL ANNOTATION
C1 [Hofer, Edith; Schmidt, Helena] Med Univ Graz, Dept Neurol, A-8036 Graz, Austria.
[Hofer, Edith] Med Univ Graz, Inst Med Informat Stat & Documentat, A-8036 Graz, Austria.
[Bis, Joshua C.; Psaty, Bruce M.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA.
[Shibata, Dean K.] Univ Washington, Dept Radiol, Seattle, WA 98195 USA.
[Longstreth, W. T., Jr.] Univ Washington, Dept Neurol & Epidemiol, Seattle, WA 98195 USA.
[DeCarli, Charles; Martinez, Oliver] Univ Calif Davis, Dept Neurol, Sacramento, CA 95817 USA.
[DeCarli, Charles; Martinez, Oliver] Univ Calif Davis, Ctr Neurosci, Sacramento, CA 95817 USA.
[Fornage, Myriam] Univ Texas Hlth Sci Ctr Houston, Brown Fdn, Inst Mol Med, Houston, TX 77030 USA.
[Fornage, Myriam] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Houston, TX 77030 USA.
[Gudnason, Vilmundur; Smith, Albert] Iceland Heart Assoc, Kopavogur, Iceland.
[Srikanth, Velandai; Moran, Chris; Thanh Phan; Beare, Richard] Monash Univ, Southern Clin Sch, Dept Med, Stroke & Ageing Res Grp, Melbourne, Vic 3004, Australia.
[Trompet, Stella; Jukema, J. Wouter] Leiden Univ, Med Ctr, Dept Cardiol, Leiden, Netherlands.
[Trompet, Stella; de Craen, Anton J. M.; Westendorp, Rudi G. J.] Leiden Univ, Med Ctr, Dept Gerontol & Geriatr, Leiden, Netherlands.
[Slagboom, P. Eline] Leiden Univ, Med Ctr, Dept Mol Epidemiol, Leiden, Netherlands.
[van Buchem, Mark] Leiden Univ, Med Ctr, Dept Radiol, Leiden, Netherlands.
[Verhaaren, Benjamin F. J.; Adams, Hieab H. H.; van Duijn, Cornelia M.; Hofman, Albert; Vernooij, Meike W.; Ikram, M. Arfan] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.
[Verhaaren, Benjamin F. J.; Adams, Hieab H. H.; Vernooij, Meike W.; Ikram, M. Arfan] Erasmus MC, Dept Radiol, Rotterdam, Netherlands.
[Niessen, Wiro J.] Erasmus MC, Dept Med Informat, Rotterdam, Netherlands.
[Wolf, Christiane; Chauhan, Ganesh; Dufouil, Carole; Debette, Stephanie] Univ Bordeaux Segalen, INSERM U897, Bordeaux, France.
[Mazoyer, Bernard] Univ Bordeaux Segalen, CNRS CEA UMR5296, Bordeaux, France.
[Tzourio, Christophe] Univ Bordeaux Segalen, INSERM U708, Bordeaux, France.
[Wolf, Christiane] Max Planck Inst Psychiat, Dept Stat Genet, D-80804 Munich, Germany.
[Yang, Qiong; Beiser, Alexa; Wang, Jing] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA.
[Amouyel, Philippe] Inst Pasteur, INSERM U744, F-59019 Lille, France.
[Buckley, Brendan M.] Natl Univ Ireland Univ Coll Cork, Dept Pharmacol & Therapeut, Cork, Ireland.
[Chauhan, Ganesh; Debette, Stephanie] Univ Paris 07, INSERM U1161, Paris, France.
[Chauhan, Ganesh; Debette, Stephanie] Univ Paris 07, Lariboisiere Hosp, Paris, France.
[van Duijn, Cornelia M.] Ctr Med Syst Biol, Leiden, Netherlands.
[Ford, Ian] Univ Glasgow, Robertson Ctr Biostat, Glasgow, Lanark, Scotland.
[Freudenberger, Paul; Toeglhofer, Anna M.; Schmidt, Helena] Med Univ Graz, Ctr Mol Med, Inst Mol Biol & Biochem, Res Unit Genet Epidemiol, Graz, Austria.
[Gottesman, Rebecca F.] Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21218 USA.
[Gudnason, Vilmundur; Smith, Albert] Univ Iceland, Reykjavik, Iceland.
[Heiss, Gerardo] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA.
[Lumley, Thomas] Univ Auckland, Dept Stat, Auckland 1, New Zealand.
[Niessen, Wiro J.] Delft Univ Technol, Fac Sci Appl, Delft, Netherlands.
[Psaty, Bruce M.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA.
[Satizabal, Claudia L.; Debette, Stephanie] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02215 USA.
[Sattar, Naveed; Stott, David J.] Fac Med, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland.
[Taylor, Kent D.] Los Angeles Biomed Res Inst, Inst Translat Genom & Populat Sci, Los Angeles, CA USA.
[Taylor, Kent D.] Harbor UCLA Med Ctr, Dept Pediat, Torrance, CA 90509 USA.
[Thomson, Russell] Menzies Res Inst, Hobart, Tas, Australia.
[Westendorp, Rudi G. J.] Univ Copenhagen, Dept Publ Hlth, Copenhagen, Denmark.
[Windham, B. Gwen; Mosley, Thomas H.] Univ Mississippi, Dept Med, Jackson, MS 39216 USA.
[Zijdenbos, Alex] Biospective Inc, Montreal, PQ, Canada.
[Beare, Richard] Royal Childrens Hosp, Murdoch Childrens Res Inst, Dev Imaging, Parkville, Vic 3052, Australia.
[Jukema, J. Wouter] Durrer Ctr Cardiogenet Res, Amsterdam, Netherlands.
[Jukema, J. Wouter] Interuniv Cardiol Inst Netherlands, Utrecht, Netherlands.
[Launer, Lenore J.] NIA, Bethesda, MD 20892 USA.
RP Schmidt, R (reprint author), Med Univ Graz, Dept Neurol, Div Neurogeriatr, Auenbruggerpl 22, A-8036 Graz, Austria.
EM reinhold.schmidt@medunigraz.at
RI Vernooij, Meike/E-4061-2016; Tzourio, christophe/B-4015-2009; Callisaya,
Michele/I-2333-2013
OI Tzourio, christophe/0000-0002-6517-2984; Callisaya,
Michele/0000-0003-2122-1622
FU National Institute on Aging (NIA) [N01-AG-12100]; National Heart, Lung,
and Blood Institute (NHLBI); NIA Intramural Research Program,
Hjartavernd; Icelandic Heart Association; Althingi (the Icelandic
Parliament); NHLBI [HHSN268201100005C, HHSN268201100006C,
HHSN268201100007C, HHSN268201100008C, HHSN268201100009C,
HHSN268201100010C, HHSN268201100011C, HHSN268201100012C, R01HL087641,
R01HL59367, R01HL086694]; National Human Genome Research Institute
[U01HG004402]; National Institutes of Health (NIH) [HHSN268200625226C];
NIH; Austrian Science Fond (Fonds zur Forderung der wissenschaftlichen
Forschung) [P20545-P05, P13180]; Medical University of Graz; NIA
[R01AG023629]; National Center for Advancing Translational Sciences,
University of California Los Angeles Clinical and Translational Science
Institute [UL1TR000124]; National Institute of Diabetes and Digestive
and Kidney Disease Diabetes Research Center [DK063491]; NHLBI's FHS
[N01-HC-25195]; Affymetrix, Inc for genotyping services [N02-HL-6-4278];
Robert Dawson Evans Endowment of the Department of Medicine at Boston
University School of Medicine; Boston Medical Center; National Institute
of NINDS [R01 NS17950]; National Institute of Aging [R01s AG08122,
AG16495, AG033193, U0149505]; Bristol-Myers Squibb; Netherlands Heart
Foundation [2001 D 032]; European commission [223004]; Netherlands
Genomics Initiative (NGI; Netherlands Consortium for Healthy Aging
grant) [050-060-810]; Netherlands Organization of Scientific Research
(Nederlandse Organisatie voor Wetenschappelijk Onderzoek)
[175.010.2005.011]; NGI/Netherlands Organization for Scientific Research
(NWO) [050-060-810]; Erasmus Medical Center; Erasmus University,
Rotterdam; Netherlands Organization for Scientific Research (NWO);
Netherlands Organization for the Health Research and Development
(ZonMw); Research Institute for Diseases in the Elderly; Ministry of
Education, Culture, and Science; Ministry for Health, Welfare, and
Sports; European Commission; Municipality of Rotterdam; Netherlands
Organization of Scientific Research (NWO) [918-46-615, 904-61-096,
904-61-133, 948-00-010]; Dutch Heart Foundation (Nederlandse
Hartstichting) [2009B102]; Dutch Technology Foundation Stichting
Technische Wetenschappen Perspectief programme ImaGene; EU; National
Health and Medical Research Council (NHMRC) [403000, 491109, 606543];
Wicking Dementia Education and Research Centre; NHMRC/National Heart
Foundation; Heart Foundation; NHMRC; Fondation pour la Recherche
Medicale; Caisse Nationale Maladie des Travailleurs Salaries, Direction
Generale de la Sante, Mutuelle Generale de l'Education Nationale,
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 Disease and Related Disorders; Institut Pasteur de Lille;
Centre National de Genotypage; French National Research Agency;
Fondation Leducq; [UL1RR025005]; [HL093029]; [HHSN268201200036C];
[HHSN268200800007C]; [N01HC55222]; [N01HC85079]; [N01HC85080];
[N01HC85081]; [N01HC85082]; [N01HC85083]; [N01HC85086];
[N01HC15103]; [U01HL080295]; [R01HL087652]; [R01HL105756];
[R01HL103612]; [R01HL120393]; [U01 HL096917]; [R01 HL093029]
FX Aging Gene-Environment Susceptibility-Reykjavik Study: The research has
been funded by the National Institute on Aging (NIA) contract
N01-AG-12100 with contributions from the National Eye Institute, the
National Institute on Deafness and Other Communication Disorders and the
National Heart, Lung, and Blood Institute (NHLBI), the NIA Intramural
Research Program, Hjartavernd (the Icelandic Heart Association), and the
Althingi (the Icelandic Parliament). Atherosclerosis Risk in Communities
Study: The research 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; and National Institutes of Health (NIH)
contract HHSN268200625226C. Infrastructure was partly supported by Grant
Number UL1RR025005, a component of the NIH and NIH Roadmap for Medical
Research. Funds for this project were also supported by grant HL093029
to Dr Fornage. Austrian Stroke Prevention Study (ASPS): The research
reported in this article was funded by the Austrian Science Fond (Fonds
zur Forderung der wissenschaftlichen Forschung) grant number P20545-P05
and P13180. The Medical University of Graz supports the databank of the
ASPS. Cardiovascular Health Study (CHS): This research was supported by
NHLBI contracts HHSN268201200036C, HHSN268200800007C, N01HC55222,
N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086,
and N01HC15103; and NHLBI grants U01HL080295, R01HL087652, R01HL105756,
R01HL103612, and R01HL120393 with additional contribution from the
National Institute of Neurological Disorders and Stroke (NINDS).
Additional support was provided through R01AG023629 from the 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, University
of California Los Angeles Clinical and Translational Science Institute
grant UL1TR000124, and the National Institute of Diabetes and Digestive
and Kidney Disease Diabetes Research Center grant DK063491 to the
Southern California Diabetes Endocrinology Research Center. The content
is solely the responsibility of the authors and does not necessarily
represent the official views of the NIH. Framingham Heart Study (FHS):
From the FHS of the NHLBI of the NIH and Boston University School of
Medicine. This work was supported by the NHLBI's FHS (contract no.
N01-HC-25195) and its contract with Affymetrix, Inc for genotyping
services (contract no. N02-HL-6-4278). A portion of this research used
the Linux Cluster for Genetic Analysis (LinGA-II) funded by the Robert
Dawson Evans Endowment of the Department of Medicine at Boston
University School of Medicine and Boston Medical Center. This study was
also supported by grants from the National Institute of NINDS (R01
NS17950), the National Institute of Aging (R01s AG08122, AG16495,
AG033193, and U0149505) and the NHLBI (U01 HL096917 and R01 HL093029).
Prospective Study of Pravastatin in the Elderly at Risk: This study was
supported by an investigator initiated grant obtained from Bristol-Myers
Squibb. Dr. Jukema is an established clinical investigator of the
Netherlands Heart Foundation (grant 2001 D 032).; Support for genotyping
was provided by the seventh framework program of the European commission
(grant 223004) and by the Netherlands Genomics Initiative (NGI;
Netherlands Consortium for Healthy Aging grant 050-060-810). Rotterdam
Study (RS): The GWA database of the RS was funded through the
Netherlands Organization of Scientific Research (Nederlandse Organisatie
voor Wetenschappelijk Onderzoek; no. 175.010.2005.011). This study was
further supported by the NGI/Netherlands Organization for Scientific
Research (NWO) project no. 050-060-810. The RS is supported by the
Erasmus Medical Center and Erasmus University, Rotterdam; the
Netherlands Organization for Scientific Research (NWO), the Netherlands
Organization for the Health Research and Development (ZonMw), the
Research Institute for Diseases in the Elderly, the Ministry of
Education, Culture, and Science, the Ministry for Health, Welfare, and
Sports, the European Commission (DG XII), and the Municipality of
Rotterdam. The Rotterdam Scan Study was supported by the Netherlands
Organization of Scientific Research (NWO) project nos. 918-46-615,
904-61-096, 904-61-133, and 948-00-010. Dr Verhaaren was supported by
the Dutch Heart Foundation (Nederlandse Hartstichting), grant number
2009B102. Erasmus Medical Center was further supported by the Dutch
Technology Foundation Stichting Technische Wetenschappen Perspectief
programme ImaGene and the EU Seventh Framework Programme for Research
(FP7) grant VPH-Dare@IT (Virtual Physiological Human: DementiA Research
Enabled By IT). Tasmanian Study of Cognition and Gait: This study is
supported by Project Grants from the National Health and Medical
Research Council (NHMRC IDs 403000, 491109, and 606543), and a grant
from the Wicking Dementia Education and Research Centre, Hobart. Dr
Srikanth is supported by an NHMRC/National Heart Foundation Career
Development Fellowship and a Heart Foundation Future Fellowship. Dr
Thomson is supported by an NHMRC Project Grant. 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, 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 Disease
and Related Disorders, the Institut Pasteur de Lille and the Centre
National de Genotypage. Dr Debette is recipient of a Chair of Excellence
grant from the French National Research Agency. Drs Tzourio and Debette
are supported by a grant from the Fondation Leducq.
NR 67
TC 3
Z9 3
U1 0
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0039-2499
EI 1524-4628
J9 STROKE
JI Stroke
PD NOV
PY 2015
VL 46
IS 11
BP 3048
EP 3057
PG 10
WC Clinical Neurology; Peripheral Vascular Disease
SC Neurosciences & Neurology; Cardiovascular System & Cardiology
GA CV0WN
UT WOS:000363974500004
PM 26451028
ER
PT J
AU Lutsep, HL
Lynn, MJ
Cotsonis, GA
Derdeyn, CP
Turan, TN
Fiorella, D
Janis, LS
Lane, BF
Montgomery, J
Chimowitz, MI
AF Lutsep, Helmi L.
Lynn, Michael J.
Cotsonis, George A.
Derdeyn, Colin P.
Turan, Tanya N.
Fiorella, David
Janis, L. Scott
Lane, Bethany F.
Montgomery, Jean
Chimowitz, Marc I.
CA SAMMPRIS Investigators
TI Does the Stenting Versus Aggressive Medical Therapy Trial Support
Stenting for Subgroups With Intracranial Stenosis?
SO STROKE
LA English
DT Article
ID ARTERIAL-STENOSIS; SAMMPRIS; STROKE
C1 [Lutsep, Helmi L.] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97239 USA.
[Lynn, Michael J.; Cotsonis, George A.; Lane, Bethany F.; Montgomery, Jean] Emory Univ, Dept Biostat & Bioinformat, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA.
[Derdeyn, Colin P.] Washington Univ, Sch Med, Dept Radiol, St Louis, MO 63110 USA.
[Turan, Tanya N.; Chimowitz, Marc I.] Med Univ S Carolina, Dept Neurol, Charleston, SC USA.
[Fiorella, David] SUNY Coll Old Westbury, Dept Neurol Surg, Old Westbury, NY USA.
[Janis, L. Scott] NIH, Bethesda, MD 20892 USA.
RP Lutsep, HL (reprint author), Oregon Hlth & Sci Univ, Oregon Stroke Ctr, 3181 SW Sam Jackson Pk Rd,CR131, Portland, OR 97239 USA.
EM lutseph@ohsu.edu
OI Turan, Tanya/0000-0001-5399-8845; Derdeyn, Colin/0000-0002-5932-2683
FU National Institute of Neurological Disorders and Stroke (NINDS) [U01
NS058728]; Stryker Neurovascular
FX Stenting Versus Aggressive Medical Therapy for Intracranial Arterial
Stenosis (SAMMPRIS) is funded by the National Institute of Neurological
Disorders and Stroke (NINDS) U01 NS058728. Stryker Neurovascular
provided study devices and supplemental funding for third party device
distribution, site monitoring, and study auditing and AstraZeneca
donated rosuvastatin (Crestor) to study patients in the SAMMPRIS trial.
NR 5
TC 7
Z9 7
U1 1
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0039-2499
EI 1524-4628
J9 STROKE
JI Stroke
PD NOV
PY 2015
VL 46
IS 11
BP 3282
EP 3284
PG 3
WC Clinical Neurology; Peripheral Vascular Disease
SC Neurosciences & Neurology; Cardiovascular System & Cardiology
GA CV0WN
UT WOS:000363974500041
PM 26382173
ER
PT J
AU Iordanskiy, S
Van Duyne, R
Sampey, GC
Woodson, CM
Fry, K
Saifuddin, M
Guo, J
Wu, YT
Romerio, F
Kashanchi, F
AF Iordanskiy, Sergey
Van Duyne, Rachel
Sampey, Gavin C.
Woodson, Caitlin M.
Fry, Kelsi
Saifuddin, Mohammed
Guo, Jia
Wu, Yuntao
Romerio, Fabio
Kashanchi, Fatah
TI Therapeutic doses of irradiation activate viral transcription and induce
apoptosis in HIV-1 infected cells
SO VIROLOGY
LA English
DT Article
DE HIV-1 latency; CD4+T cells; Monocytes; X-ray; Irradiation;
Transcription; Apoptosis; HIV-1 reactivation; Humanized mice
ID HUMAN-IMMUNODEFICIENCY-VIRUS; CD4(+) T-CELLS; HUMANIZED MOUSE MODELS;
LONG TERMINAL REPEAT; NF-KAPPA-B; HISTONE DEACETYLASE INHIBITORS;
HEMATOPOIETIC STEM-CELLS; HIV-1 TAR ELEMENT; DNA-DAMAGE; LATENT HIV
AB The highly active antiretroviral therapy reduces HIV-1 RNA in plasma to undetectable levels. However, the virus continues to persist in the long-lived resting CD4(+) T cells, macrophages and astrocytes which form a viral reservoir in infected individuals. Reactivation of viral transcription is critical since the host immune response in combination with antiretroviral therapy may eradicate the virus. Using the chronically HIV-1 infected T lymphoblastoid and monocytic cell lines, primary quiescent CD4+ T cells and humanized mice infected with dual-tropic HIV-1 89.6, we examined the effect of various X-ray irradiation (IR) doses (used for HIV-related lymphoma treatment and lower doses) on HIV-1 transcription and viability of infected cells. Treatment of both T cells and monocytes with IR, a well-defined stress signal, led to increase of HIV-1 transcription, as evidenced by the presence of RNA polymerase II and reduction of HDAC1 and methyl transferase SUV39H1 on the HIV-1 promoter. This correlated with the increased GFP signal and elevated level of intracellular HIV-1 RNA in the IR-treated quiescent CD4+ T cells infected with GFP-encoding HIV-1. Exposition of latently HIV-1infected monocytes treated with PKC agonist bryostatin 1 to IR enhanced transcription activation effect of this latency-reversing agent. Increased HIV-1 replication after IR correlated with higher cell death: the level of phosphorylated Ser46 in p53, responsible for apoptosis induction, was markedly higher in the HIV-1 infected cells following IR treatment. Exposure of HIV-1 infected humanized mice with undetectable viral RNA level to IR resulted in a significant increase of HIV-1 RNA in plasma, lung and brain tissues. Collectively, these data point to the use of low to moderate dose of IR alone or in combination with HIV-1 transcription activators as a potential application for the "Shock and Kill" strategy for latently HIV-1 infected cells. (C) 2015 Elsevier Inc. All rights reserved.
C1 [Iordanskiy, Sergey; Van Duyne, Rachel; Sampey, Gavin C.; Woodson, Caitlin M.; Fry, Kelsi; Saifuddin, Mohammed; Guo, Jia; Wu, Yuntao; Kashanchi, Fatah] George Mason Univ, Mol Virol Lab, Sch Syst Biol, Manassas, VA 20110 USA.
[Van Duyne, Rachel] NCI, Ctr Canc Res, NIH, Frederick, MD 21702 USA.
[Romerio, Fabio] Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA.
RP Kashanchi, F (reprint author), George Mason Univ, Mol Virol Lab, Discovery Hall,Room 182,10900 Univ Blvd MS 1H8, Manassas, VA 20110 USA.
EM fkashanc@gmu.edu
FU NIH [AI043894, AI114490, AI113140]
FX The following reagents were obtained through the AIDS Research and
Reference Reagent Program, Division of AIDS, NIAID, NIH: U1 and ACH-2
cells from Dr. Thomas Folks; HIV-1 89.6 dual-tropic viral strain from
Dr. Ronald Collman; anti-HIV-1 p24 mouse monoclonal antibody from Dr.
Michael Malim. The antiretrovirals lamivudine/emtricitabine, tenofovir,
indinavir, raltegravir, and maraviroc as well as LRA bryostatin 1 were
also from AIDS Research and Reference Reagent Program. The HIV-1
proviral clone NL was kindly provided by Dr. Lee Ratner. Authors are
grateful to Dr. Shabana Shabbeer Meyering for reading of the manuscript
This work was supported by NIH grants AI043894, AI114490, and AI113140
to FK. The content is solely the responsibility of the authors and does
not necessarily represent the official views of the National Institutes
of Health.
NR 119
TC 8
Z9 8
U1 0
U2 9
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0042-6822
J9 VIROLOGY
JI Virology
PD NOV
PY 2015
VL 485
BP 1
EP 15
DI 10.1016/j.virol.2015.06.021
PG 15
WC Virology
SC Virology
GA CV1DH
UT WOS:000363993100001
PM 26184775
ER
PT J
AU Johnson, RF
Via, LE
Kumar, MR
Cornish, JP
Yellayi, S
Huzella, L
Postnikova, E
Oberlander, N
Bartos, C
Ork, BL
Mazur, S
Allan, C
Holbrook, MR
Solomon, J
Johnson, JC
Pickel, J
Hensley, LE
Jahrling, PB
AF Johnson, Reed F.
Via, Laura E.
Kumar, Mia R.
Cornish, Joseph P.
Yellayi, Srikanth
Huzella, Louis
Postnikova, Elena
Oberlander, Nicholas
Bartos, Christopher
Ork, Britini L.
Mazur, Steven
Allan, Cindy
Holbrook, Michael R.
Solomon, Jeffrey
Johnson, Joshua C.
Pickel, James
Hensley, Lisa E.
Jahrling, Peter B.
TI Intratracheal exposure of common marmosets to MERS-CoV Jordan-n3/2012 or
MERS-CoV EMC/2012 isolates does not result in lethal disease
SO VIROLOGY
LA English
DT Article
DE MERS; Middle East Respiratory Syndrome; MERS-CoV; Nonhuman primate;
Animal model; Coronavirus
ID RESPIRATORY SYNDROME CORONAVIRUS; RHESUS MACAQUES; COMPUTED-TOMOGRAPHY;
SAUDI-ARABIA; EMBL-EBI; INFECTION; QUANTIFICATION; PROGRESSION;
GENERATION; MODEL
AB Middle East Respiratory Syndrome Coronavirus (MERS-CoV) continues to be a threat to human health in the Middle East. Development of countermeasures is ongoing; however, an animal model that faithfully recapitulates human disease has yet to be defined. A recent study indicated that inoculation of common marmosets resulted in inconsistent lethality. Based on these data we sought to compare two isolates of MERS-CoV. We followed disease progression in common marmosets after intratracheal exposure with: MERS-C0V-EMC/2012, MERS-CoV-Jordan-n3/202, media, or inactivated virus. Our data suggest that common marmosets developed a mild to moderate non-lethal respiratory disease, which was quantifiable by computed tomography (CT), with limited other clinical signs. Based on CT data, clinical data, and virological data, MERS-CoV inoculation of common marmosets results in mild to moderate clinical signs of disease that are likely due to manipulations of the marmoset rather than as a result of robust viral replication. Published by Elsevier Inc.
C1 [Johnson, Reed F.; Kumar, Mia R.; Cornish, Joseph P.; Jahrling, Peter B.] NIAID, Emerging Viral Pathogens Sect, NIH, Frederick, MD 21702 USA.
[Via, Laura E.] NIAID, TB Res Sect, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
[Yellayi, Srikanth; Huzella, Louis; Postnikova, Elena; Oberlander, Nicholas; Bartos, Christopher; Ork, Britini L.; Mazur, Steven; Allan, Cindy; Holbrook, Michael R.; Johnson, Joshua C.; Hensley, Lisa E.; Jahrling, Peter B.] NIAID, Integrated Res Facil, NIH, Frederick, MD USA.
[Solomon, Jeffrey] NIH, Ctr Infect Dis Imaging Radiol & Imaging Sci, Ctr Clin, Bethesda, MD 20892 USA.
[Pickel, James] NIMH, Transgen Core Facil, NIH, Bethesda, MD 20892 USA.
RP Johnson, RF (reprint author), NIAID, Emerging Viral Pathogens Sect, NIH, Frederick, MD 21702 USA.
EM johnsonreed@mail.nih.gov
FU National Institute of Allergy and Infectious Disease, Division of
Intramural Research; US National Institute of Allergy and Infectious
Diseases (NIAID) [HHSN272200700016I]
FX This work was supported by the National Institute of Allergy and
Infectious Disease, Division of Intramural Research. We are grateful to
Marisa St. Claire, Russell Byrum, Dan Ragland, and the entire EVPS and
IRF team for their contributions to these studies. We thank Jiro Wada
for his contribution to the preparation of figures and Laura Bollinger
for providing technical writing services for preparation of this
manuscript. The content of this publication does not necessarily reflect
the views or policies of the US Department of Health and Human Services
(DHHS) or of the institutions and companies affiliated with the authors.
This work was funded in part through Battelle Memorial Institute's prime
contract with the US National Institute of Allergy and Infectious
Diseases (NIAID) under Contract no. HHSN272200700016I. B.L.O., M.R.H.,
J.C.J. performed this work as employees of Battelle Memorial Institute.
Subcontractors to Battelle Memorial Institute who performed this work
are E.P. an employee of Tunnell Government Services, Inc.; N. O., S.Y.
and L.H. are employees of Charles River Laboratories, S.M. an employee
of MRI Global, CB an employee of MedRelief.
NR 23
TC 14
Z9 14
U1 0
U2 5
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0042-6822
J9 VIROLOGY
JI Virology
PD NOV
PY 2015
VL 485
BP 422
EP 430
DI 10.1016/j.virol.2015.07.013
PG 9
WC Virology
SC Virology
GA CV1DH
UT WOS:000363993100044
PM 26342468
ER
PT J
AU Silberman, Y
Fetterly, TL
Awad, EK
Milano, EJ
Usdin, TB
Winder, DG
AF Silberman, Yuval
Fetterly, Tracy L.
Awad, Elias K.
Milano, Elana J.
Usdin, Ted B.
Winder, Danny G.
TI Ethanol Produces Corticotropin-Releasing Factor Receptor-Dependent
Enhancement of Spontaneous Glutamatergic Transmission in the Mouse
Central Amygdala
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Article
DE Central Nucleus of the Amygdala; CRF Reporter Mice; Whole-Cell
Patch-Clamp Electrophysiology; Diphtheria Toxin; Selective Deletion
ID ALCOHOL DEPENDENCE; EXPRESSION; DRINKING; MODULATION; BEHAVIOR; NUCLEUS;
PATHWAY; MEDIATE; RATS; MICE
AB BackgroundEthanol (EtOH) modulation of central amygdala (CeA) neurocircuitry plays a key role in the development of alcoholism via activation of the corticotropin-releasing factor (CRF) receptor (CRFR) system. Previous work has predominantly focused on EtOHxCRF interactions on the CeA GABA circuitry; however, our laboratory recently showed that CRF enhances CeA glutamatergic transmission. Therefore, this study sought to determine whether EtOH modulates CeA glutamate transmission via activation of CRF signaling.
MethodsThe effects of EtOH on spontaneous excitatory postsynaptic currents (sEPSCs) and basal resting membrane potentials were examined via standard electrophysiology methods in adult male C57BL/6J mice. Local ablation of CeA CRF neurons (CRFCeAhDTR) was achieved by targeting the human diphtheria toxin receptor (hDTR) to CeA CRF neurons with an adeno-associated virus. Ablation was quantified post hoc with confocal microscopy. Genetic targeting of the diphtheria toxin active subunit to CRF neurons (CRFDTA mice) ablated CRF neurons throughout the central nervous system, as assessed by quantitative reverse transcriptase polymerase chain reaction quantification of CRF mRNA.
ResultsAcute bath application of EtOH significantly increased sEPSC frequency in a concentration-dependent manner in CeA neurons, and this effect was blocked by pretreatment of co-applied CRFR1 and CRFR2 antagonists. In experiments utilizing a CRF-tomato reporter mouse, EtOH did not significantly alter the basal membrane potential of CeA CRF neurons. The ability of EtOH to enhance CeA sEPSC frequency was not altered in CRFCeAhDTR mice despite a similar to 78% reduction in CeA CRF cell counts. The ability of EtOH to enhance CeA sEPSC frequency was also not altered in the CRFDTA mice despite a 3-fold reduction in CRF mRNA levels.
ConclusionsThese findings demonstrate that EtOH enhances spontaneous glutamatergic transmission in the CeA via a CRFR-dependent mechanism. Surprisingly, our data suggest that this action may not require endogenous CRF.
C1 [Silberman, Yuval; Fetterly, Tracy L.; Awad, Elias K.; Milano, Elana J.; Winder, Danny G.] Vanderbilt Univ, Sch Med, Dept Mol Physiol & Biophys, Nashville, TN 37232 USA.
[Fetterly, Tracy L.; Winder, Danny G.] Vanderbilt Univ, Sch Med, Vanderbilt Brain Inst, Nashville, TN 37232 USA.
[Usdin, Ted B.] NIMH, Sect Fundamental Neurosci, NIH, Bethesda, MD 20892 USA.
RP Winder, DG (reprint author), Vanderbilt Univ, Sch Med, Dept Mol Physiol & Biophys, 750 Robinson Res Bldg,2200 Pierce Ave, Nashville, TN 37232 USA.
EM danny.winder@vanderbilt.edu
FU Intramural NIH HHS; NIAAA NIH HHS [AA 22937, AA 20140, AA 19455, F32
AA020140, R01 AA019455, K99 AA022937]; NIDA NIH HHS [DA 19112, R01
DA019112]; NIMH NIH HHS [ZIA-MH002685]
NR 27
TC 0
Z9 0
U1 2
U2 9
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0145-6008
EI 1530-0277
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD NOV
PY 2015
VL 39
IS 11
BP 2154
EP 2162
DI 10.1111/acer.12881
PG 9
WC Substance Abuse
SC Substance Abuse
GA CU6ZR
UT WOS:000363684700012
PM 26503065
ER
PT J
AU Kessler, J
Ruggles, K
Patel, A
Nucifora, K
Li, LF
Roberts, MS
Bryant, K
Braithwaite, RS
AF Kessler, Jason
Ruggles, Kelly
Patel, Anik
Nucifora, Kimberly
Li, Lifeng
Roberts, Mark S.
Bryant, Kendall
Braithwaite, R. Scott
TI Targeting an Alcohol Intervention Cost-Effectively to Persons Living
with HIV/AIDS in East Africa
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Article
DE HIV Prevention; Alcohol; Cost-Effectiveness; Mathematical Modeling
ID SUB-SAHARAN AFRICA; FEMALE SEX WORKERS; SEXUALLY-TRANSMITTED INFECTIONS;
ANTIRETROVIRAL THERAPY; HIV-1 INFECTION; COLLABORATIVE PROJECT; NORTHERN
TANZANIA; WESTERN KENYA; RISK-FACTORS; VIRAL LOAD
AB BackgroundIn the current report, we ask if targeting a cognitive behavioral therapy (CBT)-based intervention aimed at reducing hazardous alcohol consumption to HIV-infected persons in East Africa would have a favorable value at costs that are feasible for scale-up.
MethodsUsing a computer simulation to inform HIV prevention decisions in East Africa, we compared 4 different strategies for targeting a CBT intervention(i) all HIV-infected persons attending clinic; (ii) only those patients in the pre-antiretroviral therapy (ART) stages of care; (iii) only those patients receiving ART; and (iv) only those patients with detectable viral loads (VLs) regardless of disease stage. We define targeting as screening for hazardous alcohol consumption (e.g., using the Alcohol Use Disorders Identification Test and offering the CBT intervention to those who screen positive). We compared these targeting strategies to a null strategy (no intervention) or a hypothetical scenario where an alcohol intervention was delivered to all adults regardless of HIV status.
ResultsAn intervention targeted to HIV-infected patients could prevent 18,000 new infections, add 46,000 quality-adjusted life years (QALYs), and yield an incremental cost-effectiveness ratio of $600/QALY compared to the null scenario. Narrowing the prioritized population to only HIV-infected patients in pre-ART phases of care results in 15,000 infections averted, the addition of 21,000 QALYs and would be cost-saving, while prioritizing based on an unsuppressed HIV-1 VL test results in 8,300 new infections averted, adds 6,000 additional QALYs, and would be cost-saving as well.
ConclusionsOur results suggest that targeting a cognitive-based treatment aimed at reducing hazardous alcohol consumption to subgroups of HIV-infected patients provides favorable value in comparison with other beneficial strategies for HIV prevention and control in this region. It may even be cost-saving under certain circumstances.
C1 [Kessler, Jason; Ruggles, Kelly; Patel, Anik; Nucifora, Kimberly; Li, Lifeng; Braithwaite, R. Scott] NYU, Sch Med, Dept Populat Hlth, New York, NY USA.
[Patel, Anik] Univ British Columbia, Dept Med, Vancouver, BC, Canada.
[Roberts, Mark S.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Hlth Policy & Management, Pittsburgh, PA USA.
[Bryant, Kendall] NIAAA, NIH, Bethesda, MD USA.
RP Kessler, J (reprint author), 227 E 30th St,Room 650, New York, NY 10016 USA.
EM jason.kessler@nyumc.org
RI Erita, Dewi/N-4649-2016;
OI Ruggles, Kelly/0000-0002-0152-0863
FU NIAAA NIH HHS [R01 AA017385]
NR 56
TC 2
Z9 2
U1 2
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0145-6008
EI 1530-0277
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD NOV
PY 2015
VL 39
IS 11
BP 2179
EP 2188
DI 10.1111/acer.12890
PG 10
WC Substance Abuse
SC Substance Abuse
GA CU6ZR
UT WOS:000363684700015
PM 26463727
ER
PT J
AU Lee, IH
Miller, NR
Zan, E
Tavares, F
Blitz, AM
Sung, H
Yousem, DM
Boland, MV
AF Lee, In Ho
Miller, Neil R.
Zan, Elcin
Tavares, Fabiana
Blitz, Ari M.
Sung, Heejong
Yousem, David M.
Boland, Michael V.
TI Visual Defects in Patients With Pituitary Adenomas: The Myth of
Bitemporal Hemianopsia
SO AMERICAN JOURNAL OF ROENTGENOLOGY
LA English
DT Review
DE optic chiasm; pituitary adenoma; visual deficits
ID MANAGEMENT; PATTERN
AB OBJECTIVE. The objective of this study was to test the hypothesis that bitemporal hemianopsia (BHA) is the most common visual field (VF) defect in patients with pituitary macroadenoma and to assess the degree of optic pathway compression necessary to produce visual defects.
MATERIALS AND METHODS. We reviewed the MRI findings and medical records of 119 patients with pituitary macroadenoma who had undergone formal assessment of VFs. We then evaluated the degree of optic pathway displacement caused by the pituitary macroadenoma, as observed on MR images. The classifications of optic pathway displacement included no contact, abutment but no displacement, mild displacement (< 3 mm), and moderate displacement (>= 3 mm). Qualitative analysis classified VFs as normal or as having defects that were monocular, bitemporal, mixed (bitemporal with additional defects), homonymous, or nonspecific.
RESULTS. A total of 89 of 115 patients had an abnormal VF. Only one patient had true BHA. The most common defects were bitemporal or mixed defects (in 49 of 115 patients [42.6%]), likely because more than just the chiasm is often compressed by the pituitary macroadenoma. Classification of optic pathway displacement by the pituitary macroadenoma was as follows: 23 patients had no contact, eight had abutment but no displacement, 27 had mild displacement, and 57 had moderate displacement. In 78 of the 92 patients (84.8%) with pituitary macroadenoma that had contact with the optic pathway, contact was with the optic chiasm and the prechiasmal optic nerve. Of the 49 patients with bitemporal or mixed defects, 42 had moderate displacement of the optic pathway caused by their tumors.
CONCLUSION. BHA is exceedingly uncommon in patients with pituitary macroadenoma. However, although bitemporal and mixed defects are the most common abnormal VF findings, they were found in only 42.6% of patients. Such defects rarely occur if the tumor displaces the optic pathway less than 3 mm from baseline.
C1 [Lee, In Ho; Zan, Elcin; Tavares, Fabiana; Blitz, Ari M.; Yousem, David M.] Johns Hopkins Med Inst, Russell H Morgan Dept Radiol & Radiol Sci, Baltimore, MD 21287 USA.
[Lee, In Ho] Chungnam Natl Univ Hosp, Dept Radiol, Daejeon, South Korea.
[Miller, Neil R.; Boland, Michael V.] Johns Hopkins Med Inst, Wilmer Eye Inst, Baltimore, MD 21287 USA.
[Sung, Heejong] NHGRI, Genometr Sect, Computat & Stat Genom Branch, NIH, Baltimore, MD USA.
RP Yousem, DM (reprint author), Johns Hopkins Med Inst, Russell H Morgan Dept Radiol & Radiol Sci, 600 N Wolfe St,Phipps B100F, Baltimore, MD 21287 USA.
EM dyousem1@jhu.edu
NR 17
TC 1
Z9 1
U1 1
U2 3
PU AMER ROENTGEN RAY SOC
PI RESTON
PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA
SN 0361-803X
EI 1546-3141
J9 AM J ROENTGENOL
JI Am. J. Roentgenol.
PD NOV
PY 2015
VL 205
IS 5
BP W512
EP W518
DI 10.2214/AJR.15.14527
PG 7
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA CU8SV
UT WOS:000363814900007
PM 26496573
ER
PT J
AU Schinasi, LH
De Roos, AJ
Ray, RM
Edlefsen, KL
Parks, CG
Howard, BV
Meliker, JR
Bonner, MR
Wallace, RB
LaCroix, AZ
AF Schinasi, Leah H.
De Roos, Anneclaire J.
Ray, Roberta M.
Edlefsen, Kerstin L.
Parks, Christine G.
Howard, Barbara V.
Meliker, Jaymie R.
Bonner, Matthew R.
Wallace, Robert B.
LaCroix, Andrea Z.
TI Insecticide exposure and farm history in relation to risk of lymphomas
and leukemias in the Women's Health Initiative observational study
cohort
SO ANNALS OF EPIDEMIOLOGY
LA English
DT Article
DE Pesticides; Insecticides; Women; Lymphoma; Leukemia
ID NON-HODGKINS-LYMPHOMA; OCCUPATIONAL-EXPOSURE; PESTICIDE EXPOSURE;
MULTIPLE-MYELOMA; UNITED-STATES; CANCER; MEN; METAANALYSES; MINNESOTA;
NEOPLASMS
AB Purpose: Relationships of farm history and insecticide exposure at home or work with lymphohematopoietic (LH) neoplasm risk were investigated in a large prospective cohort of US women.
Methods: In questionnaires, women self-reported history living or working on a farm, personally mixing or applying insecticides, insecticide application in the home or workplace by a commercial service, and treating pets with insecticides. Relationships with non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), diffuse large B-cell lymphoma (DLIKL), follicular lymphoma, plasma cell neoplasms, and myeloid leukemia were investigated using Cox proportional hazard models. Age and farming history were explored as effect modifiers.
Results: The analysis included 76,493 women and 822 NHL cases. Women who ever lived or worked on a farm had 1.12 times the risk of NHL (95% confidence interval [Cl] = 0.95-1.32) compared to those who did not. Women who reported that a commercial service ever applied insecticides in their immediate surroundings had 65% higher risk of CLL/SLL (95% Cl = 1.15-2.38). Women aged less than 65 years who ever applied insecticides had 87% higher risk of DLBCL (95% Cl = 1.13-3.09).
Conclusions: Insecticide exposures may contribute to risk of CLL/SLL and DLBCL Future studies should examine relationships of LH subtypes with specific types of household insecticides. (C) 2015 Elsevier Inc. All rights reserved.
C1 [Schinasi, Leah H.; De Roos, Anneclaire J.] Drexel Univ, Dept Environm & Occupat Hlth, Sch Publ Hlth, Philadelphia, PA 19104 USA.
[Ray, Roberta M.; LaCroix, Andrea Z.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA.
[Edlefsen, Kerstin L.] Univ Washington, Dept Lab Med, Seattle, WA 98195 USA.
[Parks, Christine G.] NIEHS, Epidemiol Branch, NIH, Res Triangle Pk, NC 27709 USA.
[Howard, Barbara V.] MedStar Res Inst, Dept Field Studies, Hyattsville, MD USA.
[Howard, Barbara V.] Georgetown Howard Univ Ctr Clin & Translat Sci, Washington, DC USA.
[Meliker, Jaymie R.] SUNY Stony Brook, Dept Preventat Med, Stony Brook, NY 11794 USA.
[Meliker, Jaymie R.] SUNY Stony Brook, Grad Program Publ Hlth, Stony Brook, NY 11794 USA.
[Bonner, Matthew R.] SUNY Buffalo, Dept Epidemiol & Environm Hlth, Buffalo, NY 14260 USA.
[Wallace, Robert B.] Univ Iowa, Dept Epidemiol, Coll Publ Hlth, Iowa City, IA USA.
[LaCroix, Andrea Z.] Univ Calif San Diego, Sch Med, Div Epidemiol, San Diego, CA 92103 USA.
RP Schinasi, LH (reprint author), Drexel Univ, Dept Environm & Occupat Hlth, Sch Publ Hlth, Philadelphia, PA 19104 USA.
EM lhs36@drexel.edu
OI Parks, Christine/0000-0002-5734-3456
FU National Heart, Lung, and Blood Institute, National Institutes of
Health, U.S. Department of Health and Human Services [HHSN268201100046C,
HHSN268201100001C, HHSN268201100002C, HHSN268201100003C,
HHSN268201100004C, HHSN271201100004C]; NIH, National Institute of
Environmental Health Sciences
FX The WHI program is funded by the National Heart, Lung, and Blood
Institute, National Institutes of Health, U.S. Department of Health and
Human Services through contracts HHSN268201100046C, HHSN268201100001C,
HHSN268201100002C, HHSN268201100003C, HHSN268201100004C, and
HHSN271201100004C. The research was supported in part by the Intramural
Research Program of the NIH, National Institute of Environmental Health
Sciences.
NR 32
TC 2
Z9 2
U1 0
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1047-2797
EI 1873-2585
J9 ANN EPIDEMIOL
JI Ann. Epidemiol.
PD NOV
PY 2015
VL 25
IS 11
BP 803
EP 810
DI 10.1016/j.annepidem.2015.08.002
PG 8
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA CU5WI
UT WOS:000363602300001
PM 26365305
ER
PT J
AU Saidha, S
Al-Louzi, O
Ratchford, JN
Bhargava, P
Oh, J
Newsome, SD
Prince, JL
Pham, D
Roy, S
van Zijl, P
Balcer, LJ
Frohman, EM
Reich, DS
Crainiceanu, C
Calabresi, PA
AF Saidha, Shiv
Al-Louzi, Omar
Ratchford, John N.
Bhargava, Pavan
Oh, Jiwon
Newsome, Scott D.
Prince, Jerry L.
Pham, Dzung
Roy, Snehashis
van Zijl, Peter
Balcer, Laura J.
Frohman, Elliot M.
Reich, Daniel S.
Crainiceanu, Ciprian
Calabresi, Peter A.
TI Optical coherence tomography reflects brain atrophy in multiple
sclerosis: A four-year study
SO ANNALS OF NEUROLOGY
LA English
DT Article
ID NERVE-FIBER LAYER; MICROCYSTIC MACULAR EDEMA; INNER NUCLEAR LAYER;
PATHOLOGY; THICKNESS; NEURITIS; MS; SEGMENTATION; DEGENERATION;
METAANALYSIS
AB ObjectiveThe aim of this work was to determine whether atrophy of specific retinal layers and brain substructures are associated over time, in order to further validate the utility of optical coherence tomography (OCT) as an indicator of neuronal tissue damage in patients with multiple sclerosis (MS).
MethodsCirrus high-definition OCT (including automated macular segmentation) was performed in 107 MS patients biannually (median follow-up: 46 months). Three-Tesla magnetic resonance imaging brain scans (including brain-substructure volumetrics) were performed annually. Individual-specific rates of change in retinal and brain measures (estimated with linear regression) were correlated, adjusting for age, sex, disease duration, and optic neuritis (ON) history.
ResultsRates of ganglion cell+inner plexiform layer (GCIP) and whole-brain (r=0.45; p<0.001), gray matter (GM; r=0.37; p<0.001), white matter (WM; r=0.28; p=0.007), and thalamic (r=0.38; p<0.001) atrophy were associated. GCIP and whole-brain (as well as GM and WM) atrophy rates were more strongly associated in progressive MS (r=0.67; p<0.001) than relapsing-remitting MS (RRMS; r=0.33; p=0.007). However, correlation between rates of GCIP and whole-brain (and additionally GM and WM) atrophy in RRMS increased incrementally with step-wise refinement to exclude ON effects; excluding eyes and then patients (to account for a phenotype effect), the correlation increased to 0.45 and 0.60, respectively, consistent with effect modification. In RRMS, lesion accumulation rate was associated with GCIP (r=-0.30; p=0.02) and inner nuclear layer (r=-0.25; p=0.04) atrophy rates.
InterpretationOver time GCIP atrophy appears to mirror whole-brain, and particularly GM, atrophy, especially in progressive MS, thereby reflecting underlying disease progression. Our findings support OCT for clinical monitoring and as an outcome in investigative trials. Ann Neurol 2015;78:Ann Neurol 2015;78:679-696
C1 [Saidha, Shiv; Al-Louzi, Omar; Ratchford, John N.; Bhargava, Pavan; Oh, Jiwon; Newsome, Scott D.; Reich, Daniel S.; Calabresi, Peter A.] Johns Hopkins Univ, Dept Neurol, Baltimore, MD 21287 USA.
[Prince, Jerry L.; Pham, Dzung; Roy, Snehashis] Johns Hopkins Univ, Dept Elect & Comp Engn, Baltimore, MD 21287 USA.
[Prince, Jerry L.] Johns Hopkins Univ, Dept Comp Sci, Baltimore, MD 21287 USA.
[Prince, Jerry L.; Pham, Dzung; Roy, Snehashis; van Zijl, Peter; Reich, Daniel S.] Johns Hopkins Univ, Dept Radiol & Radiol Sci, Baltimore, MD 21287 USA.
[Pham, Dzung; Roy, Snehashis] Henry M Jackson Fdn Adv Mil Med, Ctr Neurosci & Regenerat Med, Bethesda, MD USA.
[Balcer, Laura J.] NYU, Dept Neurol, Langone Med Ctr, New York, NY 10016 USA.
[Frohman, Elliot M.] Univ Texas Southwestern, Dept Neurol & Ophthalmol, Dallas, TX USA.
[Reich, Daniel S.; Crainiceanu, Ciprian] Johns Hopkins Univ, Dept Biostat, Baltimore, MD 21287 USA.
[Reich, Daniel S.] NINDS, Translat Neuroradiol Unit, Bethesda, MD 20892 USA.
RP Saidha, S (reprint author), Johns Hopkins Univ, 600 North Wolfe St,Pathol 627, Baltimore, MD 21287 USA.
EM ssaidha2@jhmi.edu
RI Reich, Daniel/E-5701-2010;
OI Reich, Daniel/0000-0002-2628-4334; Roy, Snehashis/0000-0002-7997-3993
FU Race to Erase MS; National Institutes of Health [5R01NS082347-02,
R01NS070906]; National Multiple Sclerosis Society [TR 3760-A-3, RG
4212-A-4]; National Eye Institute [R01 EY 014993, R01 EY 019473];
Braxton Debbie Angela Dillon and Skip (DADS) Donor Advisor Fund;
Intramural Research Program of NINDS
FX This study was funded by the Race to Erase MS (to S.S.), National
Institutes of Health (5R01NS082347-02 [to P.A.C.] and R01NS070906 [to
D.P.]), National Multiple Sclerosis Society (TR 3760-A-3 [to P.A.C.] and
RG 4212-A-4 [to L.J.B. subcontracted to P.A.C.]), National Eye Institute
(R01 EY 014993 and R01 EY 019473 [to L.J.B. subcontracted to P.A.C.]),
Braxton Debbie Angela Dillon and Skip (DADS) Donor Advisor Fund (to
P.A.C., E.M.F., and L.J.B.), and the Intramural Research Program of
NINDS (to D.S.R.).
NR 53
TC 25
Z9 25
U1 0
U2 4
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 NOV
PY 2015
VL 78
IS 5
BP 801
EP 813
DI 10.1002/ana.24487
PG 13
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA CU7NP
UT WOS:000363727900014
PM 26190464
ER
PT J
AU Boufraqech, M
Kebebew, E
AF Boufraqech, Myriem
Kebebew, Electron
TI New genomic somatic amplifications and deletions in papillary thyroid
cancer
SO ENDOCRINE
LA English
DT Editorial Material
ID RISK
C1 [Boufraqech, Myriem; Kebebew, Electron] NCI, NIH, Bethesda, MD 20892 USA.
RP Kebebew, E (reprint author), NCI, NIH, Bethesda, MD 20892 USA.
EM kebebewe@mail.nih.gov
RI Boufraqech, Myriem/E-4823-2016
FU Intramural NIH HHS [ZIA BC011275-03]
NR 10
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1355-008X
EI 1559-0100
J9 ENDOCRINE
JI Endocrine
PD NOV
PY 2015
VL 50
IS 2
BP 270
EP 271
DI 10.1007/s12020-015-0704-9
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA CU4HP
UT WOS:000363488800003
PM 26224588
ER
PT J
AU Stratakis, CA
AF Stratakis, Constantine A.
TI A giant? Think of genetics: growth hormone-producing adenomas in the
young are almost always the result of genetic defects
SO ENDOCRINE
LA English
DT Editorial Material
ID MCCUNE-ALBRIGHT-SYNDROME; PITUITARY-ADENOMAS; MOLECULAR-GENETICS; CARNEY
COMPLEX; MUTATIONS; CDKN1B; AIP; TUMORS; MEN1
C1 Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Dev Endocrinol & Genet PDEGEN, Sect Endocrinol & Genet SEGEN, NIH,East Labs, Bethesda, MD 20892 USA.
RP Stratakis, CA (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Dev Endocrinol & Genet PDEGEN, Sect Endocrinol & Genet SEGEN, NIH,East Labs, CRC Rm 1-3330,Bldg 10-CRC,10 Ctr Dr, Bethesda, MD 20892 USA.
EM stratakc@mail.nih.gov
FU Intramural NIH HHS; NICHD NIH HHS [Z01 HD008920-04]
NR 17
TC 3
Z9 3
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1355-008X
EI 1559-0100
J9 ENDOCRINE
JI Endocrine
PD NOV
PY 2015
VL 50
IS 2
BP 272
EP 275
DI 10.1007/s12020-015-0645-3
PG 4
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA CU4HP
UT WOS:000363488800004
PM 26054904
ER
PT J
AU Gelinas, L
AF Gelinas, Luke
TI Frames, Choice-Reversal, and Consent
SO ETHICAL THEORY AND MORAL PRACTICE
LA English
DT Article
DE Consent; Framing effects; Autonomy; Rights
AB Recently Jason Hanna has argued that a particular type of susceptibility to framing effects-namely, the tendency to reverse one's choice between certain logically equivalent frames-invalidates actual tokens of consent. Here I argue that this claim is false: proneness to choice-reversal per se between the relevant types of frames does not invalidate consent.
C1 NIH, Dept Bioeth, Bethesda, MD 20892 USA.
RP Gelinas, L (reprint author), NIH, Dept Bioeth, 10 Ctr Dr,Bldg 10,Room 1C118, Bethesda, MD 20892 USA.
EM lukegelinas@gmail.com
NR 9
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 1386-2820
EI 1572-8447
J9 ETHICAL THEORY MORAL
JI Ethical Theory Moral Pract.
PD NOV
PY 2015
VL 18
IS 5
BP 1049
EP 1057
DI 10.1007/s10677-015-9581-9
PG 9
WC Philosophy
SC Philosophy
GA CU4GO
UT WOS:000363485800011
ER
PT J
AU Prasad, V
Bilal, U
AF Prasad, Vinay
Bilal, Usama
TI The role of censoring on progression free survival: Oncologist
discretion advised
SO EUROPEAN JOURNAL OF CANCER
LA English
DT Editorial Material
DE Censoring; Progression free survival; Informative censoring; BOLERO-2;
Randomised trial design; Surrogacy
ID TRIALS
AB Censoring is increasingly appreciated as a potential bias affecting estimates of progression free survival (PFS) in randomised trials. In this commentary, we explore the central assumption of censoring. Censored patients are considered no more or less likely to undergo the event of interest than those who remain in the analysis. Instead however, if one makes alternate assumptions, that censored patients are different than those who remain on the trial, estimates of PFS change. Using the example of the recent BOLERO-2 trial of exemestane and everolimus, we show that by altering the assumptions for censoring, the major conclusions of clinical trials may change. As such, the number of censored patients at each time interval should be routinely reported in randomised trials to better understand the implications of censoring. Published by Elsevier Ltd.
C1 [Prasad, Vinay] NCI, Med Oncol Serv, NIH, Bethesda, MD 20892 USA.
[Bilal, Usama] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA.
RP Prasad, V (reprint author), NCI, Med Oncol Serv, NIH, 10 Ctr Dr 10-12N226, Bethesda, MD 20892 USA.
EM vinayak.prasad@nih.gov
OI Bilal, Usama/0000-0002-9868-7773
NR 8
TC 2
Z9 2
U1 0
U2 1
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0959-8049
EI 1879-0852
J9 EUR J CANCER
JI Eur. J. Cancer
PD NOV
PY 2015
VL 51
IS 16
BP 2269
EP 2271
DI 10.1016/j.ejca.2015.07.005
PG 3
WC Oncology
SC Oncology
GA CU3ZY
UT WOS:000363466800001
PM 26259493
ER
PT J
AU Prasad, V
AF Prasad, Vinay
TI Non-invasive, serum DNA pregnancy testing leading to incidental
discovery of cancer: A good thing?
SO EUROPEAN JOURNAL OF CANCER
LA English
DT Editorial Material
DE Non-invasive pregnancy tests; Genetic testing; Unintended consequences;
Lead-time bias; Overdiagnosis
AB Cell-free DNA for perinatal screening is a growing industry. Non-invasive prenatal testing (NIPT) is based on the premise that foetal DNA is able to cross the placental barrier and enter the mother's circulation, where it can be examined for chromosomal abnormalities, such as trisomy 13, 18 or 21. Such tests are expected to be widely used by pregnant women, with the annual market expected to surpass $1 billion. Recently, a number of case reports have emerged in the haematology-oncology literature. The routine use of NIPT has led to the discovery of maternal neoplasms. Most writers have concluded that this is yet another benefit of the test; however, a closer examination of the cases reveals that this incidental detection may not improve patient outcomes. In some cases, early detection provides lead time bias, but does not change the ultimate clinical outcome, and in other cases, detection constitutes earlier knowledge of a cancer whose natural history cannot be altered. Here, we explore in detail cases where cancer was incidentally discovered among women undergoing routine non-invasive pregnancy testing, and investigate whether or not these women were benefitted by the discovery. Published by Elsevier Ltd.
C1 NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA.
RP Prasad, V (reprint author), NCI, Med Oncol Branch, NIH, 10 Ctr Dr 10-12N226, Bethesda, MD 20892 USA.
EM vinayak.prasad@nih.gov
NR 7
TC 1
Z9 1
U1 1
U2 13
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0959-8049
EI 1879-0852
J9 EUR J CANCER
JI Eur. J. Cancer
PD NOV
PY 2015
VL 51
IS 16
BP 2272
EP 2274
DI 10.1016/j.ejca.2015.07.029
PG 3
WC Oncology
SC Oncology
GA CU3ZY
UT WOS:000363466800002
PM 26278647
ER
PT J
AU Giaccone, G
Bazhenova, LA
Nemunaitis, J
Tan, M
Juhasz, E
Ramlau, R
van den Heuvel, MM
Lal, R
Kloecker, GH
Eaton, KD
Chu, Q
Dunlop, DJ
Jain, M
Garon, EB
Davis, CS
Carrier, E
Moses, SC
Shawler, DL
Fakhrai, H
AF Giaccone, G.
Bazhenova, L. A.
Nemunaitis, J.
Tan, M.
Juhasz, E.
Ramlau, R.
van den Heuvel, M. M.
Lal, R.
Kloecker, G. H.
Eaton, K. D.
Chu, Q.
Dunlop, D. J.
Jain, M.
Garon, E. B.
Davis, C. S.
Carrier, E.
Moses, S. C.
Shawler, D. L.
Fakhrai, H.
TI A phase III study of belagenpumatucel-L, an allogeneic tumour cell
vaccine, as maintenance therapy for non-small cell lung cancer
SO EUROPEAN JOURNAL OF CANCER
LA English
DT Article
DE Non-small cell lung cancer; Cancer vaccine; Cancer immunotherapy; Cancer
gene therapy; TGF-beta
ID CLINICAL-TRIAL; CHEMOTHERAPY; CISPLATIN; PEPTIDE; MULTICENTER;
VINORELBINE; INDUCTION; RESPONSES; DURATION; EFFICACY
AB Background: Treatment options after first-line chemotherapy are limited in non-small cell lung cancer (NSCLC). Belagenpumatucel-L is a therapeutic vaccine comprised of 4 transforming growth factor (TGF)-beta 2-antisense gene-modified, irradiated, allogeneic NSCLC cell lines that may be useful for maintenance after initial treatment.
Methods: Stage III/IV NSCLC patients who did not progress after platinum-based chemotherapy were randomised 1:1 to receive maintenance belagenpumatucel-L or placebo. Patients were eligible for randomisation between one and four months from the end of induction chemotherapy. The primary endpoint was overall survival.
Results: This phase III trial enrolled 270 patients in the belagenpumatucel-L arm and 262 in the control arm. Belagenpumatucel-L was well tolerated with no serious safety concerns. There was no difference in survival between the arms (median survival 20.3 versus 17.8 months with belagenpumatucel-L versus placebo, respectively; hazard ratio (HR) 0.94, p = 0.594). There were also no differences in progression-free survival (4.3 months versus 4.0 for belagenpumatucel-L vs placebo, respectively; HR 0.99, p = 0.947). A prespecified Cox regression analysis demonstrated that the time elapsed between randomisation and the end of induction chemotherapy had a significant impact on survival (p = 0.002) and that prior radiation was a positive prognostic factor (median survival 28.4 months with belagenpumatucel-L versus 16.0 months with placebo; HR 0.61, p = 0.032).
Conclusions: Although the overall trial did not meet its survival endpoint, improved survival for belagenpumatucel-L is suggested in patients who were randomised within 12 weeks of completion of chemotherapy and in those who had received prior radiation. Further studies of belagenpumatucel-L in NSCLC are warranted. (C) 2015 Published by Elsevier Ltd.
C1 [Giaccone, G.] NCI, Bethesda, MD 20892 USA.
[Bazhenova, L. A.] Univ Calif San Diego, Moores Canc Ctr, La Jolla, CA 92093 USA.
[Nemunaitis, J.] Mary Crowley Canc Res Ctr, Dallas, TX USA.
[Tan, M.] Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC 20007 USA.
[Juhasz, E.] Koranyi Natl Inst TB & Pulmonol, Budapest, Hungary.
[Ramlau, R.] Poznan Univ Med Sci, Wielkopolskie Ctr Pulmonol & Torakochirurg, Poznan, Poland.
[van den Heuvel, M. M.] Antoni van Leeuwenhoek Hosp, Netherlands Canc Inst, Thorac Oncol, Amsterdam, Netherlands.
[Lal, R.] Kings Hlth Partners, Guys Hosp, London, England.
[Kloecker, G. H.] Univ Louisville, James Graham Brown Canc, Louisville, KY 40292 USA.
[Eaton, K. D.] Univ Washington, Seattle Canc Care Alliance, Seattle, WA 98195 USA.
[Chu, Q.] Cross Canc Inst, Edmonton, AB T6G 1Z2, Canada.
[Dunlop, D. J.] Royal Infirm, Glasgow G31 2ER, Lanark, Scotland.
[Jain, M.] Noble Hosp, Pune, Maharashtra, India.
[Garon, E. B.] Univ Calif Los Angeles, Los Angeles, CA USA.
[Davis, C. S.] CSD Biostat, Tucson, AZ USA.
[Carrier, E.; Moses, S. C.; Shawler, D. L.; Fakhrai, H.] NovaRx Corp, San Diego, CA USA.
RP Giaccone, G (reprint author), Georgetown Univ, Lombardi Comprehens Canc Ctr, 3970 Reservoir Rd, Washington, DC 20007 USA.
EM gg496@georgetown.edu
RI Giaccone, Giuseppe/E-8297-2017
OI Giaccone, Giuseppe/0000-0002-5023-7562
FU NCI NIH HHS [R44 CA096025]
NR 38
TC 25
Z9 28
U1 0
U2 6
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0959-8049
EI 1879-0852
J9 EUR J CANCER
JI Eur. J. Cancer
PD NOV
PY 2015
VL 51
IS 16
BP 2321
EP 2329
DI 10.1016/j.ejca.2015.07.035
PG 9
WC Oncology
SC Oncology
GA CU3ZY
UT WOS:000363466800009
PM 26283035
ER
PT J
AU Jaskolski, M
Miller, M
Rao, JKM
Gustchina, A
Wlodawer, A
AF Jaskolski, Mariusz
Miller, Maria
Rao, J. K. Mohana
Gustchina, Alla
Wlodawer, Alexander
TI Elucidation of the structure of retroviral proteases: areminiscence
SO FEBS JOURNAL
LA English
DT Editorial Material
DE crystal structures; drug design; HIV; inhibitors; protease
ID HUMAN-IMMUNODEFICIENCY-VIRUS; SYNTHETIC HIV-1 PROTEASE; RESOLUTION
X-RAY; CRYSTAL-STRUCTURE; ASPARTIC PROTEINASES; DRUG DESIGN; INHIBITOR;
COMPLEX; AIDS; EVOLUTIONARY
AB Determinations of only a very few protein structures had consequences comparable to the impact exerted by the structure of the protease encoded by HIV-1, published just over 25years ago. The structure of this relatively small protein and its cousins from other retroviruses provided a clear target for a spectacularly successful structure-assisted drug design effort that offered new hope for controlling the then-escalating AIDS epidemic. This reminiscence is limited primarily to work conducted at the National Cancer Institute, and is not meant to be a comprehensive history of the field, but is rather an attempt to provide a very personal account of how the structures of this most thoroughly studied crystallographic target were determined.
C1 [Jaskolski, Mariusz] Polish Acad Sci, A Mickiewicz Univ & Ctr Biocrystallog Res, Fac Chem, Inst Bioorgan Chem,Dept Crystallog, PL-61704 Poznan, Poland.
[Miller, Maria; Rao, J. K. Mohana; Gustchina, Alla; Wlodawer, Alexander] NCI, Macromol Crystallog Lab, Frederick, MD 21701 USA.
RP Jaskolski, M (reprint author), Polish Acad Sci, A Mickiewicz Univ & Ctr Biocrystallog Res, Fac Chem, Inst Bioorgan Chem,Dept Crystallog, Ul Noskowskiego 12-14, PL-61704 Poznan, Poland.
EM mariuszj@amu.edu.pl; wlodawer@nih.gov
RI Miller, Maria/I-1636-2013
OI Miller, Maria/0000-0003-0252-5348
NR 36
TC 2
Z9 2
U1 0
U2 10
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1742-464X
EI 1742-4658
J9 FEBS J
JI FEBS J.
PD NOV
PY 2015
VL 282
IS 21
BP 4059
EP 4066
DI 10.1111/febs.13397
PG 8
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA CU5RG
UT WOS:000363589100001
PM 26258480
ER
PT J
AU El Haj, M
Antoine, P
Kapogiannis, D
AF El Haj, Mohamad
Antoine, Pascal
Kapogiannis, Dimitrios
TI Flexibility decline contributes to similarity of past and future
thinking in Alzheimer's disease
SO HIPPOCAMPUS
LA English
DT Article
DE Alzheimer's disease; binding; flexibility; future thinking; hippocampus
ID MEDIAL TEMPORAL-LOBE; MILD COGNITIVE IMPAIRMENT; MEMORY BINDING
DEFICITS; MENTAL TIME-TRAVEL; AUTOBIOGRAPHICAL MEMORY; EPISODIC MEMORY;
NEURODEGENERATIVE DISEASES; AUTONOETIC CONSCIOUSNESS; HIPPOCAMPAL
DYSFUNCTION; ASSOCIATIVE MEMORY
AB A striking similarity has been suggested between past and future thinking in Alzheimer's Disease (AD), a similarity attributable to abnormalities in common modular cognitive functions and neuroanatomical substrates. This study extends this literature by identifying specific executive function deficits underlying past and future thinking in AD. Twenty-four participants with a clinical diagnosis of probable (mild) AD and 26 older controls generated past and future events and underwent tests of binding and the executive functions of flexibility, inhibition, and updating. AD patients showed similar autobiographical performances in past and future event generation, and so did control participants. In each group, the similarity of past and future thinking was predicted by flexibility. Furthermore, AD patients with low flexibility showed higher similarity of past and future thinking than those with high flexibility. These findings are interpreted in terms of involvement of the hippocampus and frontal lobes in future thinking. Deficits in these brain regions in AD are likely to compromise the ability to recombine episodic information into novel and flexible configurations as scenarios for the future. (c) 2015 Wiley Periodicals, Inc.
C1 [El Haj, Mohamad; Antoine, Pascal] Univ Lille, Res Unit Cognit & Affect Sci, Lab SCALab CNRS UMR 9193, Dept Psychol, Lille, France.
[Kapogiannis, Dimitrios] NIA, Neurosci Lab, Dept Neurosci, Baltimore, MD 21224 USA.
RP El Haj, M (reprint author), Univ Lille 3, Dept Psychol, BP 60149, F-59653 Villeneuve Dascq, France.
EM mohamad.elhaj@univ-lille3.fr
OI el haj, mohamad/0000-0001-7635-7557
FU LABEX (excellence laboratory, program investment for the future) DISTALZ
(Development of Innovative Strategies for a Transdisciplinary approach
to Alzheimer disease); National Institute on Aging; National Institutes
of Health
FX Grant sponsors: LABEX (excellence laboratory, program investment for the
future) DISTALZ (Development of Innovative Strategies for a
Transdisciplinary approach to Alzheimer disease), and intramural Program
of the National Institute on Aging; National Institutes of Health.
NR 75
TC 11
Z9 11
U1 3
U2 8
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1050-9631
EI 1098-1063
J9 HIPPOCAMPUS
JI Hippocampus
PD NOV
PY 2015
VL 25
IS 11
BP 1447
EP 1455
DI 10.1002/hipo.22465
PG 9
WC Neurosciences
SC Neurosciences & Neurology
GA CU6YW
UT WOS:000363682300024
PM 25850800
ER
PT J
AU Chen, BA
Panther, L
Marzinke, MA
Hendrix, CW
Hoesley, CJ
van der Straten, A
Husnik, MJ
Soto-Torres, L
Nel, A
Johnson, S
Richardson-Harman, N
Rabe, LK
Dezzutti, CS
AF Chen, Beatrice A.
Panther, Lori
Marzinke, Mark A.
Hendrix, Craig W.
Hoesley, Craig J.
van der Straten, Ariane
Husnik, Marla J.
Soto-Torres, Lydia
Nel, Annalene
Johnson, Sherri
Richardson-Harman, Nicola
Rabe, Lorna K.
Dezzutti, Charlene S.
CA Microbicide Trials Network
TI Phase 1 Safety, Pharmacokinetics, and Pharmacodynamics of Dapivirine and
Maraviroc Vaginal Rings: A Double-Blind Randomized Trial
SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES
LA English
DT Article
DE microbicide; pre-exposure prophylaxis; dapivirine; maraviroc; vaginal
rings; ex vivo challenge assay
ID REVERSE-TRANSCRIPTASE INHIBITOR; FEMALE GENITAL-TRACT; HIV-NEGATIVE
WOMEN; PREEXPOSURE PROPHYLAXIS; MICROBICIDE GEL; MS/MS METHOD; HUMAN
PLASMA; INFECTION; PREVENTION; QUANTIFICATION
AB Background:Variable adherence limits effectiveness of daily oral and intravaginal tenofovir-containing pre-exposure prophylaxis. Monthly vaginal antiretroviral rings are one approach to improve adherence and drug delivery.Methods:MTN-013/IPM 026, a multisite, double-blind, randomized, placebo-controlled trial in 48 HIV-negative US women, evaluated vaginal rings containing dapivirine (DPV) (25 mg) and maraviroc (MVC) (100 mg), DPV only, MVC only, and placebo used continuously for 28 days. Safety was assessed by adverse events. Drug concentrations were quantified in plasma, cervicovaginal fluid (CVF), and cervical tissue. Cervical biopsy explants were challenged with HIV ex vivo to evaluate pharmacodynamics.Results:There was no difference in related genitourinary adverse events between treatment arms compared with placebo. DPV and MVC concentrations rose higher initially before falling more rapidly with the combination ring compared with relatively stable concentrations with the single-drug rings. DPV concentrations in CVF were 1 and 5 log(10) greater than cervical tissue and plasma for both rings. MVC was consistently detected only in CVF. DPV and MVC CVF and DPV tissue concentrations dropped rapidly after ring removal. Cervical tissue showed a significant inverse linear relationship between HIV replication and DPV levels.Conclusions:In this first study of a combination microbicide vaginal ring, all 4 rings were safe and well tolerated. Tissue DPV concentrations were 1000 times greater than plasma concentrations and single drug rings had more stable pharmacokinetics. DPV, but not MVC, demonstrated concentration-dependent inhibition of HIV-1 infection in cervical tissue. Because MVC concentrations were consistently detectable only in CVF and not in plasma, improved drug release of MVC rings is needed.
C1 [Chen, Beatrice A.; Dezzutti, Charlene S.] Univ Pittsburgh, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA USA.
[Chen, Beatrice A.; Rabe, Lorna K.; Dezzutti, Charlene S.] Magee Womens Res Inst, Pittsburgh, PA USA.
[Panther, Lori] Fenway Inst, Dept Med & Infect Dis, Boston, MA USA.
[Marzinke, Mark A.; Hendrix, Craig W.] Johns Hopkins Univ, Dept Pathol & Med, Baltimore, MD USA.
[Hoesley, Craig J.] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA.
[van der Straten, Ariane] Womens Global Hlth Imperat WGHI RTI Int, San Francisco, CA USA.
[van der Straten, Ariane] Univ Calif San Francisco, Ctr AIDS Prevent Studies, Dept Med, San Francisco, CA USA.
[Husnik, Marla J.] Fred Hutchinson Canc Res Ctr, Stat Ctr HIV AIDS Res & Prevent, Seattle, WA 98104 USA.
[Soto-Torres, Lydia] NIAID, DAIDS, Bethesda, MD 20892 USA.
[Nel, Annalene] Int Partnership Microbicides, Silver Spring, MD USA.
[Johnson, Sherri] FHI 360, Durham, NC USA.
[Richardson-Harman, Nicola] Alpha StatConsult, Damascus, MD USA.
RP Chen, BA (reprint author), Magee Womens Hosp, 300 Halket St, Pittsburgh, PA 15213 USA.
EM chenba@upmc.edu
RI Hendrix, Craig/G-4182-2014
OI Hendrix, Craig/0000-0002-5696-8665
FU National Institute of Allergy and Infectious Diseases of the U.S.
National Institutes of Health [UM1AI068633, UM1AI068615, UM1AI106707];
Eunice Kennedy Shriver National Institute of Child Health and Human
Development of the U.S. National Institutes of Health; National
Institute of Mental Health of the U.S. National Institutes of Health;
Gilead Sciences
FX The study was designed and implemented by the Microbicide Trials Network
(MTN). The MTN is funded by the National Institute of Allergy and
Infectious Diseases (UM1AI068633, UM1AI068615, UM1AI106707), with
co-funding from the Eunice Kennedy Shriver National Institute of Child
Health and Human Development and the National Institute of Mental
Health, all components of the U.S. National Institutes of Health. The
vaginal rings used in this study were supplied by the IND sponsor,
International Partnership for Microbicides (IPM).; N.R.-H. was a paid
consultant for the pharmacodynamic data analysis. C.W.H. has received
research support from Gilead Sciences managed through Johns Hopkins
University. The remaining authors have no conflicts of interest to
disclose.
NR 33
TC 23
Z9 23
U1 1
U2 7
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1525-4135
EI 1077-9450
J9 JAIDS-J ACQ IMM DEF
JI JAIDS
PD NOV 1
PY 2015
VL 70
IS 3
BP 242
EP 249
DI 10.1097/QAI.0000000000000702
PG 8
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA CU6ID
UT WOS:000363634600004
PM 26034880
ER
PT J
AU Onabajo, OO
Porter-Gill, P
Paquin, A
Rao, NN
Liu, LY
Tang, W
Brand, N
Prokunina-Olsson, L
AF Onabajo, Olusegun O.
Porter-Gill, Patricia
Paquin, Ashley
Rao, Nina
Liu, Luyang
Tang, Wei
Brand, Nathan
Prokunina-Olsson, Ludmila
TI Expression of Interferon Lambda 4 Is Associated with Reduced
Proliferation and Increased Cell Death in Human Hepatic Cells
SO JOURNAL OF INTERFERON AND CYTOKINE RESEARCH
LA English
DT Article
ID C VIRUS-INFECTION; SPONTANEOUS CLEARANCE; ANTIVIRAL ACTIVITY;
GENETIC-VARIATION; STIMULATED GENES; VIRAL CLEARANCE; HCV; GENOTYPE;
IL28B; IFN-LAMBDA-4
AB Interferon lambda 4 (IFN-4) is a novel type-III interferon that can be generated only in individuals carrying a G frame-shift allele of an exonic genetic variant (rs368234815-G/TT). The rs368234815-G allele is strongly associated with decreased clearance of hepatitis C virus (HCV) infection. Here, we further explored the biological function of IFN-4 expressed in human hepatic cellsa hepatoma cell line HepG2 and fresh primary human hepatocytes (PHHs). We performed live confocal imaging, cell death and proliferation assays, mRNA expression profiling, protein detection, and antibody blocking assays using transient and inducible stable in vitro systems. Not only did we observe significant intracellular retention of IFN-4 but also detected secreted IFN-4 in the culture media of expressing cells. Secreted IFN-4 induced strong activation of the interferon-stimulated genes (ISGs) in IFN-4-expressing and surrounding cells in transwell assays. Specifically, in PHHs, secreted IFN-4 induced expression of the CXCL10 transcript and a corresponding pro-inflammatory chemokine, IP-10. In IFN-4-expressing HepG2 cells, we also observed decreased proliferation and increased cell death. All IFN-4-induced phenotypesactivation of ISGs, decreased proliferation, and increased cell deathcould be inhibited by an anti-IFN-4-specific antibody. Our study offers new insights into biology of IFN-4 and its possible role in HCV clearance.
C1 [Onabajo, Olusegun O.; Porter-Gill, Patricia; Paquin, Ashley; Rao, Nina; Liu, Luyang; Tang, Wei; Brand, Nathan; Prokunina-Olsson, Ludmila] NCI, Lab Translat Genom, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
RP Prokunina-Olsson, L (reprint author), NCI, Lab Translat Genom, Div Canc Epidemiol & Genet, NIH, 8717 Grovemont Circle, Bethesda, MD 20892 USA.
EM prokuninal@mail.nih.gov
FU Intramural Research Program (IRP) of the Division of Cancer Epidemiology
and Genetics, National Cancer Institute, National Institutes of Health,
US; NCI Director's Innovation Award; NCI Director's Career Development
Award
FX The work has been supported by the Intramural Research Program (IRP) of
the Division of Cancer Epidemiology and Genetics, National Cancer
Institute, National Institutes of Health, US, by the NCI Director's
Innovation Award to L.P.-O., and the NCI Director's Career Development
Award to O.O.O. The authors thank Adeola Obajemu for technical help and
staff of the Protein Expression Laboratory and Protein Characterization
Laboratory, Frederick National Laboratory for Cancer Research for help
with development of stable inducible HepG2 cell lines.
NR 42
TC 7
Z9 8
U1 0
U2 4
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1079-9907
EI 1557-7465
J9 J INTERF CYTOK RES
JI J. Interferon Cytokine Res.
PD NOV 1
PY 2015
VL 35
IS 11
BP 888
EP 900
DI 10.1089/jir.2014.0161
PG 13
WC Biochemistry & Molecular Biology; Cell Biology; Immunology
SC Biochemistry & Molecular Biology; Cell Biology; Immunology
GA CU8BL
UT WOS:000363766000006
PM 26134097
ER
PT J
AU Robbins, HA
Clarke, CA
Arron, ST
Tatalovich, Z
Kahn, AR
Hernandez, BY
Paddock, L
Yanik, EL
Lynch, CF
Kasiske, BL
Snyder, J
Engels, EA
AF Robbins, Hilary A.
Clarke, Christina A.
Arron, Sarah T.
Tatalovich, Zaria
Kahn, Amy R.
Hernandez, Brenda Y.
Paddock, Lisa
Yanik, Elizabeth L.
Lynch, Charles F.
Kasiske, Bertram L.
Snyder, Jon
Engels, Eric A.
TI Melanoma Risk and Survival among Organ Transplant Recipients
SO JOURNAL OF INVESTIGATIVE DERMATOLOGY
LA English
DT Article
ID CHRONIC LYMPHOCYTIC-LEUKEMIA; CUTANEOUS MELANOMA; MALIGNANT-MELANOMA;
SKIN-CANCER; RENAL-TRANSPLANTATION; MELANOCYTIC NEVI; KIDNEY; EXPOSURE;
EXCESS; IMMUNOSUPPRESSION
AB Solid organ transplant recipients, who are medically immunosuppressed to prevent graft rejection, have increased melanoma risk, but risk factors and outcomes are incompletely documented. We evaluated melanoma incidence among 139,991 non-Hispanic white transplants using linked US transplant-cancer registry data (1987-2010). We used standardized incidence ratios (SIRs) to compare incidence with the general population and incidence rate ratios (IRRs) from multivariable Poisson models to assess risk factors. Separately, we compared post-melanoma survival among transplant recipients (n=182) and non-recipients (n=131,358) using multivariable Cox models. Among transplant recipients, risk of invasive melanoma (n=519) was elevated (SIR= 2.20, 95% Cl 2.01-2.39), especially for regional stage tumors (SIR= 4.11, 95% Cl 3.27-5.09). Risk of localized tumors was stable over time after transplantation but higher with azathioprine maintenance therapy (IRR= 1.35, 95% Cl 1.03-1.77). Risk of regional/distant stage tumors peaked within 4 years following transplantation and increased with polyclonal antibody induction therapy (IRR=1.65, 95% Cl 1.02-2.67). Melanoma-specific mortality was higher among transplant recipients than non-recipients (hazard ratio 2.98, 95% CI 2.26-3.93). Melanoma exhibits increased incidence and aggressive behavior under transplant-related immunosuppression. Some localized melanomas may result from azathioprine, which acts synergistically with UV radiation, whereas T-cell depleting induction therapies may promote late-stage tumors. Our findings support sun safety practices and skin screening for transplant recipients.
C1 [Robbins, Hilary A.; Yanik, Elizabeth L.; Engels, Eric A.] NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA.
[Clarke, Christina A.] Canc Prevent Inst Calif, Fremont, CA USA.
[Clarke, Christina A.] Stanford Univ, Sch Med, Dept Hlth Res & Policy, Palo Alto, CA 94304 USA.
[Clarke, Christina A.] Stanford Canc Inst, Palo Alto, CA USA.
[Arron, Sarah T.] Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA.
[Tatalovich, Zaria] NCI, Div Canc Control & Populat Sci, NIH, Rockville, MD USA.
[Kahn, Amy R.] New York State Canc Registry, Albany, NY USA.
[Hernandez, Brenda Y.] Univ Hawaii, Ctr Canc, Honolulu, HI 96822 USA.
[Paddock, Lisa] New Jersey State Canc Registry, Trenton, NJ USA.
[Paddock, Lisa] Rutgers Sch Publ Hlth, Piscataway, NJ USA.
[Lynch, Charles F.] Univ Iowa, Dept Epidemiol, Iowa City, IA USA.
[Kasiske, Bertram L.] Univ Minnesota, Hennepin Cty Med Ctr, Dept Med, Minneapolis, MN 55415 USA.
[Snyder, Jon] Minneapolis Med Res Fdn Inc, Sci Registry Transplant Recipients, Minneapolis, MN USA.
RP Robbins, HA (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, 9609 Med Ctr Dr,6-E228, Bethesda, MD 20892 USA.
EM hilary.robbins@jhmi.edu
OI Yanik, Elizabeth/0000-0002-5835-0201
FU National Cancer Institute; Minneapolis Medical Research Foundation,
Minneapolis, MN, USA [HHSH250201000018C]; Arbor Research Collaborative
for Health in Ann Arbor, MI, USA [HHSH234200537009C]; SEER Program of
the National Cancer Institute: California [HHSN261201000036C,
HHSN261201000035C, HHSN261201000-034C]; SEER Program of the National
Cancer Institute: Connecticut [HHSN261201000024C]; SEER Program of the
National Cancer Institute: Hawaii [HHSN261201-000037C, N01-PC-35137,
N01-PC-35139]; SEER Program of the National Cancer Institute: Iowa
[HSN261201000032C, N01-PC-35143]; SEER Program of the National Cancer
Institute: New Jersey [HHSN261201300021I, N01-PC-2013-00021]; SEER
Program of the National Cancer Institute: Seattle-Puget Sound
[N01-PC-35142]; SEER Program of the National Cancer Institute: Utah
[HHSN26120-13000171]; National Program of Cancer Registries of the
Centers for Disease Control and Prevention: California [1U58
DP000807-01]; National Program of Cancer Registries of the Centers for
Disease Control and Prevention: Colorado [U58 DP000848-04]; National
Program of Cancer Registries of the Centers for Disease Control and
Prevention: Georgia [5U58DP003875-01]; National Program of Cancer
Registries of the Centers for Disease Control and Prevention: Illinois
[5U58DP003883-03]; National Program of Cancer Registries of the Centers
for Disease Control and Prevention: Maryland [U58DP12-1205 3919-03];
National Program of Cancer Registries of the Centers for Disease Control
and Prevention: Michigan [5U58DP003921-03]; National Program of Cancer
Registries of the Centers for Disease Control and Prevention: New Jersey
[5U58/DP003931-02]; National Program of Cancer Registries of the Centers
for Disease Control and Prevention: New York [U58DP003879]; National
Program of Cancer Registries of the Centers for Disease Control and
Prevention: North Carolina [U58DP000832]; National Program of Cancer
Registries of the Centers for Disease Control and Prevention: Texas
[5U58DP000824-04]; state of California; state of Colorado; state of
Connecticut; state of Illinois; state of Iowa; state of Massachusetts
(Massachusetts Cancer Prevention and Control Cooperative Agreement)
[5458DP003920]; state of New Jersey; state of New York; state of Cancer
Surveillance Initiative; state of Texas; state of Utah; state of
Washington; state of University of Utah; state of Fred Hutchinson Cancer
Research Center in Seattle, WA, USA
FX This research was supported in part by the Intramural Research Program
of the National Cancer Institute. We gratefully acknowledge the support
and assistance provided by individuals at the Health Resources and
Services Administration (Monica Lin), the SRTR (Ajay Israni, Paul
Newkirk), and the following cancer registries: the states of California,
Colorado (Jack Finch), Connecticut (Lou Gonsalves), Georgia (Rana
Bayakly), Hawaii, Iowa, and Illinois (Lori Koch), Michigan (Glenn
Copeland), New Jersey (Xiaoling Niu), New York and North Carolina
(Chandrika Rao), Texas (Melanie Williams), and Utah (Janna Harrell), and
the Seattle-Puget Sound area of Washington (Margaret Madeleine). We also
thank analysts at Information Management Services for programming
support (David Castenson, Matthew Chaloux, Michael Curry, and Ruth
Parsons). The SRTR is currently operated under the contract number
HHSH250201000018C (Health Resources and Services Administration) by the
Minneapolis Medical Research Foundation, Minneapolis, MN, USA. During
the initial period when registry linkages were performed, the SRTR was
managed by Arbor Research Collaborative for Health in Ann Arbor, MI, USA
(contract number HHSH234200537009C). The following cancer registries
were supported by the SEER Program of the National Cancer Institute:
California (contract numbers HHSN261201000036C, HHSN261201000035C, and
HHSN261201000-034C), Connecticut (HHSN261201000024C), Hawaii
(HHSN261201-000037C, N01-PC-35137, and N01-PC-35139), Iowa
(HSN261201000032C and N01-PC-35143), New Jersey (HHSN261201300021I,
N01-PC-2013-00021), Seattle-Puget Sound (N01-PC-35142), and Utah
(HHSN26120-13000171). The following cancer registries were supported by
the National Program of Cancer Registries of the Centers for Disease
Control and Prevention: California (agreement 1U58 DP000807-01),
Colorado (U58 DP000848-04), Georgia (5U58DP003875-01), Illinois
(5U58DP003883-03), Maryland (U58DP12-1205 3919-03), Michigan
(5U58DP003921-03), New Jersey (5U58/DP003931-02), New York
(U58DP003879), North Carolina (U58DP000832), and Texas
(5U58DP000824-04). Additional support was provided by the states of
California, Colorado, Connecticut, Illinois, Iowa, Massachusetts
(Massachusetts Cancer Prevention and Control Cooperative Agreement
5458DP003920), New Jersey, New York (including the Cancer Surveillance
Initiative), Texas, Utah, and Washington, as well as the University of
Utah and Fred Hutchinson Cancer Research Center in Seattle, WA, USA.
NR 50
TC 11
Z9 11
U1 1
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-202X
EI 1523-1747
J9 J INVEST DERMATOL
JI J. Invest. Dermatol.
PD NOV
PY 2015
VL 135
IS 11
BP 2657
EP 2665
DI 10.1038/jid.2015.312
PG 9
WC Dermatology
SC Dermatology
GA CV1DM
UT WOS:000363993600017
PM 26270022
ER
PT J
AU Dao, L
Glancy, B
Lucotte, B
Chang, LC
Balaban, RS
Hsu, LY
AF Dao, Lam
Glancy, Brian
Lucotte, Bertrand
Chang, Lin-Ching
Balaban, Robert S.
Hsu, Li-Yueh
TI A Model-based approach for microvasculature structure distortion
correction in two-photon fluorescence microscopy images
SO JOURNAL OF MICROSCOPY
LA English
DT Article
DE Distortion Correction; image deconvolution and restoration; vascular
Imaging
ID POINT-SPREAD FUNCTIONS; IN-VIVO; CONFOCAL MICROSCOPY; BLIND
DECONVOLUTION; EXCITATION; RESTORATION; CAPILLARIES
AB This paper investigates a postprocessing approach to correct spatial distortion in two-photon fluorescence microscopy images for vascular network reconstruction. It is aimed at in vivo imaging of large field-of-view, deep-tissue studies of vascular structures. Based on simple geometric modelling of the object-of-interest, a distortion function is directly estimated from the image volume by deconvolution analysis. Such distortion function is then applied to subvolumes of the image stack to adaptively adjust for spatially varying distortion and reduce the image blurring through blind deconvolution. The proposed technique was first evaluated in phantom imaging of fluorescent microspheres that are comparable in size to the underlying capillary vascular structures. The effectiveness of restoring three-dimensional (3D) spherical geometry of the microspheres using the estimated distortion function was compared with empirically measured point-spread function. Next, the proposed approach was applied to in vivo vascular imaging of mouse skeletal muscle to reduce the image distortion of the capillary structures. We show that the proposed method effectively improve the image quality and reduce spatially varying distortion that occurs in large field-of-view deep-tissue vascular dataset. The proposed method will help in qualitative interpretation and quantitative analysis of vascular structures from fluorescence microscopy images.
Lay Description Image distortion in fluorescence microscopy affects qualitative interpretation and particularly quantitative comparison of biological structures. Conventional image deconvolution approaches using empirically measured point-spread function (PSF) from submicron beads have limitations in correcting for large structural distortion in in vivo deep-tissue scans that require spatially varying models of the PSF. In this paper, we present a model-based image restoration approach to reduce spatial distortion and image blurring of microvascular structures in two-photon fluorescence microscopy images. Our results showed significant improvement in quantitative geometry measurements of the microsphere phantom compared to conventional measured PSF approach. We also showed that the method improve the image quality of vessel structures in mouse skeletal muscle. This image restoration approach can assist in qualitative and quantitative analysis of large field-of-view deep-tissue two photon fluorescence microscopy images.
C1 [Dao, Lam; Glancy, Brian; Lucotte, Bertrand; Balaban, Robert S.; Hsu, Li-Yueh] NHLBI, Cardiac Energet Lab, NIH, Bethesda, MD 20892 USA.
[Dao, Lam; Chang, Lin-Ching] Catholic Univ Amer, Dept Elect Engn & Comp Sci, Washington, DC 20064 USA.
RP Hsu, LY (reprint author), NHLBI, NIH, Bldg 10,Rm B1D416,MSC 1061,10 Ctr Dr, Bethesda, MD 20892 USA.
EM lyhsu@mail.nih.gov
RI Glancy, Brian/P-3163-2016
OI Glancy, Brian/0000-0002-8571-244X
FU Intramural NIH HHS [Z99 HL999999]
NR 35
TC 0
Z9 0
U1 2
U2 9
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0022-2720
EI 1365-2818
J9 J MICROSC-OXFORD
JI J. Microsc..
PD NOV
PY 2015
VL 260
IS 2
BP 180
EP 193
DI 10.1111/jmi.12281
PG 14
WC Microscopy
SC Microscopy
GA CU4UH
UT WOS:000363525400008
PM 26224257
ER
PT J
AU Avenevoli, S
Blader, JC
Leibenluft, E
AF Avenevoli, Shelli
Blader, Joseph C.
Leibenluft, Ellen
TI Irritability in Youth: An Update
SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY
LA English
DT Editorial Material
C1 [Avenevoli, Shelli] NIMH, Dev Trajectories Mental Disorders Branch, Div Translat Res, Bethesda, MD 20892 USA.
[Blader, Joseph C.] Meadows Fdn, San Antonio, TX USA.
[Blader, Joseph C.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA.
[Leibenluft, Ellen] NIMH, Sect Bipolar Spectrum Disorders, Emot & Dev Branch, Intramural Res Program, Bethesda, MD 20892 USA.
RP Avenevoli, S (reprint author), 6001 Execut Blvd, Bethesda, MD USA.
FU National Institutes of Health; Texas State Health and Human Service
Commission
FX Dr. Blader has received research grant support from the National
Institutes of Health and has received research and service funding from
the Texas State Health and Human Service Commission. He is employed by
the State of Texas and is affiliated with the State University of New
York at Stony Brook and with the North Shore-LIJ Health System. Drs.
Avenevoli and Leibenluft report no biomedical financial interests or
potential conflicts of interest.
NR 6
TC 0
Z9 0
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0890-8567
EI 1527-5418
J9 J AM ACAD CHILD PSY
JI J. Am. Acad. Child Adolesc. Psychiatr.
PD NOV
PY 2015
VL 54
IS 11
BP 881
EP 883
DI 10.1016/j.jaac.2015.08.012
PG 3
WC Psychology, Developmental; Pediatrics; Psychiatry
SC Psychology; Pediatrics; Psychiatry
GA CU8ZA
UT WOS:000363831400002
PM 26506577
ER
PT J
AU Zou, MJ
Baitei, EY
Al-Rijjal, RA
Parhar, RS
Al-Mohanna, FA
Kimura, S
Pritchard, C
BinEssa, H
Alanazi, AA
Alzahrani, AS
Akhtar, M
Assiri, AM
Meyer, BF
Shi, YF
AF Zou, Minjing
Baitei, Essa Y.
Al-Rijjal, Roua A.
Parhar, Ranjit S.
Al-Mohanna, Futwan A.
Kimura, Shioko
Pritchard, Catrin
BinEssa, Huda
Alanazi, Azizah A.
Alzahrani, All S.
Akhtar, Mohammed
Assiri, Abdullah M.
Meyer, Brian F.
Shi, Yufei
TI KRAS(G12D)-mediated oncogenic transformation of thyroid follicular cells
requires long-term TSH stimulation and is regulated by SPRY1
SO LABORATORY INVESTIGATION
LA English
DT Article
ID MTS1 GENE OVEREXPRESSION; TRANSGENIC MICE; PHOSPHATIDYLINOSITOL
3-KINASE; THYROGLOBULIN PROMOTER; THYROTROPIN RECEPTOR; SIGNALING
PATHWAY; TUMOR INITIATION; RAS ONCOGENE; MOUSE MODEL; MAP KINASE
AB KRAS(G12D) can cause lung cancer rapidly, but is not sufficient to induce thyroid cancer. It is not clear whether long-term serum thyroid stimulating hormone (TSH) stimulation can promote KRAS(G12D)-mediated thyroid follicular cell transformation. In the present study, we investigated the effect of long-term TSH stimulation in KRAS(G12D) knock-in mice and the role of Sprouty1 (SPRY1) in KRAS(G12D)-mediated signaling. We used TPO-KRAS(G12D) mice for thyroid-specific expression of KRAS(G12D) under the endogenous KRAS promoter. Twenty TPO-KRAS(G12D) mice were given anti-thyroid drug propylthiouracil (PTU, 0.1% w/v) in drinking water to induce serum TSH and 20 mice were without PTU treatment. Equal number of wild-type littermates (TPO-KRAS(WT)) was given the same treatment. The expression of SPRY1, a negative regulator of receptor tyrosine kinase (RTK) signaling, was analyzed in both KRAS(G12D)-and BRAF(V600E)-induced thyroid cancers. Without PTU treatment, only mild thyroid enlargement and hyperplasia were observed in TPO-KRAS(G12D) mice. With PTU treatment, significant thyroid enlargement and hyperplasia occurred in both TPO-KRAS(G12D) and TPO-KRAS(WT) littermates. Thyroids from TPO-KRAS(G12D) mice were six times larger than TPO-KRAS(WT) littermates. Distinct thyroid histology was found between TPO-KRAS(G12D) and TPO-KRAS(WT) mice: thyroid from TPO-KRAS(G12D) mice showed hyperplasia with well-maintained follicular architecture whereas in TPO-KRAS(WT) mice this structure was replaced by papillary hyperplasia. Among 10 TPO-KRAS(G12D) mice monitored for 14 months, two developed follicular thyroid cancer (FTC), one with pulmonary metastasis. Differential SPRY1 expression was demonstrated: increased in FTC and reduced in papillary thyroid cancer (PTC). The increased SPRY1 expression in FTC promoted TSH-RAS signaling through PI3K/AKT pathway whereas downregulation of SPRY1 by BRAF(V600E) in PTC resulted in both MAPK and PI3K/AKT activation. We conclude that chronic TSH stimulation can enhance KRAS(G12D)-mediated oncogenesis, leading to FTC. SPRY1 may function as a molecular switch to control MAPK signaling and its downregulation by BRAF(V600E) favors PTC development.
C1 [Zou, Minjing; Baitei, Essa Y.; Al-Rijjal, Roua A.; BinEssa, Huda; Meyer, Brian F.; Shi, Yufei] King Faisal Specialist Hosp & Res Ctr, Dept Genet, Riyadh 11211, Saudi Arabia.
[Parhar, Ranjit S.] King Faisal Specialist Hosp & Res Ctr, Dept Cell Biol, Riyadh 11211, Saudi Arabia.
[Al-Mohanna, Futwan A.; Alanazi, Azizah A.; Alzahrani, All S.] King Faisal Specialist Hosp & Res Ctr, Dept Med, Riyadh 11211, Saudi Arabia.
[Kimura, Shioko] NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Pritchard, Catrin] Univ Leicester, Dept Biochem, Leicester LE1 7RH, Leics, England.
[Akhtar, Mohammed] King Faisal Specialist Hosp & Res Ctr, Dept Pathol, Riyadh 11211, Saudi Arabia.
[Assiri, Abdullah M.] King Faisal Specialist Hosp & Res Ctr, Dept Comparat Med, Riyadh 11211, Saudi Arabia.
RP Shi, YF (reprint author), King Faisal Specialist Hosp & Res Ctr, Dept Genet, POB 3354, Riyadh 11211, Saudi Arabia.
EM yufei@kfshrc.edu.sa
FU KACST grants [11-BIO1434-20, PL-10-0051]
FX The study is supported by KACST grants (11-BIO1434-20 and PL-10-0051).
We would like to thank Dr Mario Encinas for critical discussions.
NR 48
TC 0
Z9 0
U1 4
U2 5
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0023-6837
EI 1530-0307
J9 LAB INVEST
JI Lab. Invest.
PD NOV
PY 2015
VL 95
IS 11
BP 1269
EP 1277
DI 10.1038/labinvest.2015.90
PG 9
WC Medicine, Research & Experimental; Pathology
SC Research & Experimental Medicine; Pathology
GA CU8ZB
UT WOS:000363831500005
PM 26146959
ER
PT J
AU Li, MF
Toombes, GES
Silberberg, SD
Swartz, KJ
AF Li, Mufeng
Toombes, Gilman E. S.
Silberberg, Shai D.
Swartz, Kenton J.
TI Physical basis of apparent pore dilation of ATP-activated P2X receptor
channels
SO NATURE NEUROSCIENCE
LA English
DT Article
ID ION-CHANNEL; PERMEABILITY DYNAMICS; POTASSIUM CHANNEL; MEMBRANE PATCHES;
CYTOSOLIC DOMAIN; OPEN STATE; SELECTIVITY; CELLS; PERMEATION; MECHANISM
AB The selectivity of ion channels is fundamental for their roles in electrical and chemical signaling and in ion homeostasis. Although most ion channels exhibit stable ion selectivity, the prevailing view of purinergic P2X receptor channels, transient receptor potential V1 (TRPV1) channels and acid-sensing ion channels (ASICs) is that their ion conduction pores dilate upon prolonged activation. We investigated this mechanism in P2X receptors and found that the hallmark shift in equilibrium potential observed with prolonged channel activation does not result from pore dilation, but from time-dependent alterations in the concentration of intracellular ions. We derived a physical model to calculate ion concentration changes during patch-clamp recordings, which validated our experimental findings and provides a quantitative guideline for effectively controlling ion concentration. Our results have fundamental implications for understanding ion permeation and gating in P2X receptor channels, as well as more broadly for using patch-clamp techniques to study ion channels and neuronal excitability.
C1 [Li, Mufeng; Toombes, Gilman E. S.; Silberberg, Shai D.; Swartz, Kenton J.] NINDS, Mol Physiol & Biophys Sect, Porter Neurosci Res Ctr, NIH, Bethesda, MD 20892 USA.
RP Swartz, KJ (reprint author), NINDS, Mol Physiol & Biophys Sect, Porter Neurosci Res Ctr, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
EM kenton.swartz@nih.gov
OI Toombes, Gilman/0000-0001-8346-1790
FU Intramural Research Program of the National Institute of Neurological
Disorders and Stroke, US National Institutes of Health; K99 Pathway
[NS070954]
FX We thank M. Mayer, J. Minden, A. Jara-Osequera and members of the Swartz
lab for discussions. This work was supported by the Intramural Research
Program of the National Institute of Neurological Disorders and Stroke,
US National Institutes of Health (K.J.S.) and by K99 Pathway to
Independence award NS070954 (M.L.).
NR 50
TC 18
Z9 18
U1 2
U2 7
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1097-6256
EI 1546-1726
J9 NAT NEUROSCI
JI Nat. Neurosci.
PD NOV
PY 2015
VL 18
IS 11
BP 1577
EP 1583
DI 10.1038/nn.4120
PG 7
WC Neurosciences
SC Neurosciences & Neurology
GA CU8YT
UT WOS:000363830700015
PM 26389841
ER
PT J
AU Marquardt, JU
Andersen, JB
Thorgeirsson, SS
AF Marquardt, Jens U.
Andersen, Jesper B.
Thorgeirsson, Snorri S.
TI Functional and genetic deconstruction of the cellular origin in liver
cancer
SO NATURE REVIEWS CANCER
LA English
DT Review
ID GROWTH-FACTOR RECEPTOR; FACTOR-KAPPA-B; FIBROLAMELLAR
HEPATOCELLULAR-CARCINOMA; HEPATIC STELLATE CELLS; INTRAHEPATIC
CHOLANGIOCARCINOMA; STEM-CELLS; PROGENITOR-CELL; HEPATOCYTE
DIFFERENTIATION; HUMAN HEPATOCARCINOGENESIS; INACTIVATING MUTATIONS
AB During the past decade, research on primary liver cancers has particularly highlighted the uncommon plasticity of differentiated parenchymal liver cells (that is, hepatocytes and cholangiocytes (also known as biliary epithelial cells)), the role of liver progenitor cells in malignant transformation, the importance of the tumour microenvironment and the molecular complexity of liver tumours. Whereas other reviews have focused on the landscape of genetic alterations that promote development and progression of primary liver cancers and the role of the tumour microenvironment, the crucial importance of the cellular origin of liver cancer has been much less explored. Therefore, in this Review, we emphasize the importance and complexity of the cellular origin in tumour initiation and progression, and attempt to integrate this aspect with recent discoveries in tumour genomics and the contribution of the disrupted hepatic microenvironment to liver carcinogenesis.
C1 [Marquardt, Jens U.] Johannes Gutenberg Univ Mainz, Dept Med 1, D-55131 Mainz, Germany.
[Andersen, Jesper B.] Univ Copenhagen, BRIC, DK-2200 Copenhagen N, Denmark.
[Thorgeirsson, Snorri S.] NCI, Expt Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA.
RP Thorgeirsson, SS (reprint author), NCI, Expt Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA.
EM snorri_thorgeirsson@nih.gov
OI Andersen , Jesper B/0000-0003-1760-5244
FU Center for Cancer Research, National Cancer Institute, Bethesda,
Maryland, USA; German Research Foundation [MA 4443/2-1]; German Cancer
Aid [DKH 110989]; Volkswagen Foundation (Lichtenberg program); Danish
Cancer Society (Knaek cancer program); Novo Nordisk Foundation
(Hallas-Moller fellowship); Danish Medical Research Council (Sapere Aude
program); A.P. Moller Foundation
FX This project was supported by the Intramural Research Program of the
Center for Cancer Research, National Cancer Institute, Bethesda,
Maryland, USA (to S.S.T.). J.U.M. is supported by grants from the German
Research Foundation (MA 4443/2-1), German Cancer Aid (DKH 110989) and
the Volkswagen Foundation (Lichtenberg program). J.B.A. is supported by
grants from the Danish Cancer Society (Knaek cancer program), the Novo
Nordisk Foundation (Hallas-Moller fellowship), the Danish Medical
Research Council (Sapere Aude program) and the A.P. Moller Foundation.
NR 146
TC 29
Z9 29
U1 6
U2 30
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1474-175X
EI 1474-1768
J9 NAT REV CANCER
JI Nat. Rev. Cancer
PD NOV
PY 2015
VL 15
IS 11
BP 653
EP 667
DI 10.1038/nrc4017
PG 15
WC Oncology
SC Oncology
GA CU7BV
UT WOS:000363691100006
PM 26493646
ER
PT J
AU O'Shea, J
AF O'Shea, John
TI A FIRST LOOK AT T-H CELL TRANSCRIPTOMES
SO NATURE REVIEWS IMMUNOLOGY
LA English
DT News Item
C1 NIAMSD, NIH, Bethesda, MD 20892 USA.
RP O'Shea, J (reprint author), NIAMSD, NIH, Bethesda, MD 20892 USA.
EM John.Oshea@nih.gov
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 1474-1733
EI 1474-1741
J9 NAT REV IMMUNOL
JI Nat. Rev. Immunol.
PD NOV
PY 2015
VL 15
IS 11
BP 668
EP 668
DI 10.1038/nri3913
PG 1
WC Immunology
SC Immunology
GA CU7CG
UT WOS:000363692400005
PM 26403100
ER
PT J
AU Viani, RM
Alvero, C
Fenton, T
Acosta, EP
Hazra, R
Townley, E
Steimers, D
Min, S
Wiznia, A
AF Viani, Rolando M.
Alvero, Carmelita
Fenton, Terry
Acosta, Edward P.
Hazra, Rohan
Townley, Ellen
Steimers, Debra
Min, Sherene
Wiznia, Andrew
CA P1093 Study Team
TI Safety, Pharmacokinetics and Efficacy of Dolutegravir in
Treatment-experienced HIV-1 Infected Adolescents Forty-eight-week
Results from IMPAACT P1093
SO PEDIATRIC INFECTIOUS DISEASE JOURNAL
LA English
DT Article
DE antiretroviral agents; dolutegravir; HIV integrase inhibitors; pediatric
HIV; adolescent HIV
ID HIV-INFECTED CHILDREN; ACTIVE ANTIRETROVIRAL THERAPY; ONCE-DAILY
DOLUTEGRAVIR; NAIVE ADULTS; DOUBLE-BLIND; COMBINATION THERAPY;
RALTEGRAVIR; RESISTANCE; ELVITEGRAVIR; TRIAL
AB Objective: To assess the pharmacokinetics (PK), safety and efficacy of dolutegravir plus optimized background regimen in HIV-infected treatment-experienced adolescents.
Methods: Children older than 12 to younger than 18 years received dolutegravir weight-based fixed doses at approximately 1.0mg/kg once daily in a phase I/II multicenter open label 48-week study. Intensive PK evaluation was done at steady state after dolutegravir was added to a failing regimen or started at the end of a treatment interruption. Safety and HIV RNA and CD4 cell count assessments were performed through week 48.
Results: Twenty-three adolescents were enrolled and 22 (96%) completed the 48-week study visit. Median age and weight were 15 years and 52kg, respectively. Median [interquartile range (IQR)] baseline CD4+ cell count was 466 cells/L (297, 771). Median (IQR) baseline HIV-1 RNA log(10) was 4.3 log(10) copies/mL (3.9, 4.6). Dolutegravir geometric mean of the area under the plasma concentration-time curve from time of administration to 24 hours after dosing (AUC(0-24)) and 24 hour postdose concentration (C-24) were 46.0 g hours/mL and 0.90 g/mL, respectively, which were within the study targets based on adult PK ranges. Virologic success with an HIV RNA <400 copies/mL was achieved in 74% [95% confidence interval (CI): 52-90%] at week 48. Additionally, 61% (95% CI: 39-80%) had an HIV RNA <50 copies/mL at week 48. Median (IQR) gain in CD4 cell count at week 48 was 84 cells/L (-81, 238). Dolutegravir was well tolerated, with no grade 4 adverse events, serious adverse events or discontinuations because of serious adverse events.
Conclusions: Dolutegravir achieved target PK exposures in adolescents. Dolutegravir was safe and well tolerated, providing good virologic efficacy through week 48.
C1 [Viani, Rolando M.] Univ Calif San Diego, Dept Pediat, San Diego, CA 92103 USA.
[Viani, Rolando M.] Rady Childrens Hosp San Diego, La Jolla, CA USA.
[Alvero, Carmelita; Fenton, Terry] Harvard Univ, Sch Publ Hlth, Stat & Data Anal Ctr, Boston, MA 02115 USA.
[Acosta, Edward P.] Univ Alabama Birmingham, Birmingham, AL USA.
[Hazra, Rohan] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Maternal & Pediat Infect Dis Branch, NIH, Bethesda, MD USA.
[Townley, Ellen] NIAID, HJF DAIDS, Div Aids, Bethesda, MD 20892 USA.
[Steimers, Debra; Min, Sherene] GlaxoSmithKline, Res Triangle Pk, NC USA.
[Wiznia, Andrew] Albert Einstein Coll Med, Jacobi Med Ctr, Bronx, NY 10467 USA.
RP Viani, RM (reprint author), Univ Calif San Diego, Sch Med, Div Infect Dis, Dept Pediat, 9500 Gilman Dr,MC 0672, La Jolla, CA 92093 USA.
EM rolandoviani1@gmail.com
FU National Institute of Allergy and Infectious Diseases (NIAID) of the
National Institutes of Health (NIH) [UM1AI068632, UM1AI068616,
UM1AI106716]; Eunice Kennedy Shriver National Institute of Child Health
and Human Development (NICHD); National Institute of Mental Health
(NIMH); ViiV Healthcare
FX Overall support for the International Maternal Adolescent AIDS Clinical
Trials (IMPAACT) Group was provided by the National Institute of Allergy
and Infectious Diseases (NIAID) of the National Institutes of Health
(NIH) under Award Numbers UM1AI068632 (IMPAACT LOC), UM1AI068616
(IMPAACT SDMC) and UM1AI106716 (IMPAACT LC), with co-funding from the
Eunice Kennedy Shriver National Institute of Child Health and Human
Development (NICHD) and the National Institute of Mental Health (NIMH).
The content is solely the responsibility of the authors and does not
necessarily represent the official views of the NIH. Additional funding
support was provided by ViiV Healthcare. The authors have no conflict of
interest or funding to disclose, except for Debra Steimers and Sherene
Min who are GSK employees and own stock and/or stock options in the
company.
NR 31
TC 1
Z9 1
U1 2
U2 6
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0891-3668
EI 1532-0987
J9 PEDIATR INFECT DIS J
JI Pediatr. Infect. Dis. J.
PD NOV
PY 2015
VL 34
IS 11
BP 1207
EP 1213
DI 10.1097/INF.0000000000000848
PG 7
WC Immunology; Infectious Diseases; Pediatrics
SC Immunology; Infectious Diseases; Pediatrics
GA CU4WF
UT WOS:000363530500012
PM 26244832
ER
PT J
AU Vrentas, C
Ghirlando, R
Keefer, A
Hu, ZL
Tomczak, A
Gittis, AG
Murthi, A
Garboczi, DN
Gottesman, S
Leppla, SH
AF Vrentas, Catherine
Ghirlando, Rodolfo
Keefer, Andrea
Hu, Zonglin
Tomczak, Aurelie
Gittis, Apostolos G.
Murthi, Athulaprabha
Garboczi, David N.
Gottesman, Susan
Leppla, Stephen H.
TI Hfqs in Bacillus anthracis: Role of protein sequence variation in the
structure and function of proteins in the Hfq family
SO PROTEIN SCIENCE
LA English
DT Article
DE Hfq; small RNA; sRNA; Bacillus anthracis; anthrax; pXO1
ID RNA-BINDING PROPERTIES; ESCHERICHIA-COLI HFQ; SM-LIKE PROTEIN;
CLOSTRIDIUM-DIFFICILE; CHAPERONE HFQ; LSM PROTEINS; BACTERIA; HEXAMER;
IMPACT
AB Hfq proteins in Gram-negative bacteria play important roles in bacterial physiology and virulence, mediated by binding of the Hfq hexamer to small RNAs and/or mRNAs to post-transcriptionally regulate gene expression. However, the physiological role of Hfqs in Gram-positive bacteria is less clear. Bacillus anthracis, the causative agent of anthrax, uniquely expresses three distinct Hfq proteins, two from the chromosome (Hfq1, Hfq2) and one from its pXO1 virulence plasmid (Hfq3). The protein sequences of Hfq1 and 3 are evolutionarily distinct from those of Hfq2 and of Hfqs found in other Bacilli. Here, the quaternary structure of each B. anthracis Hfq protein, as produced heterologously in Escherichia coli, was characterized. While Hfq2 adopts the expected hexamer structure, Hfq1 does not form similarly stable hexamers in vitro. The impact on the monomer-hexamer equilibrium of varying Hfq C-terminal tail length and other sequence differences among the Hfqs was examined, and a sequence region of the Hfq proteins that was involved in hexamer formation was identified. It was found that, in addition to the distinct higher-order structures of the Hfq homologs, they give rise to different phenotypes. Hfq1 has a disruptive effect on the function of E. coli Hfq in vivo, while Hfq3 expression at high levels is toxic to E. coli but also partially complements Hfq function in E. coli. These results set the stage for future studies of the roles of these proteins in B. anthracis physiology and for the identification of sequence determinants of phenotypic complementation.
C1 [Vrentas, Catherine; Keefer, Andrea; Hu, Zonglin; Murthi, Athulaprabha; Leppla, Stephen H.] NIAID, NIH, Bethesda, MD 20892 USA.
[Ghirlando, Rodolfo] NIDDK, Bethesda, MD 20892 USA.
[Tomczak, Aurelie] NIAID, Bethesda, MD 20892 USA.
[Gittis, Apostolos G.; Garboczi, David N.] NIAID, Struct Biol Sect, Res Technol Branch, NIH, Rockville, MD USA.
[Gottesman, Susan] NCI, NIH, Bethesda, MD 20892 USA.
RP Leppla, SH (reprint author), NIAID, NIH, 33 North Dr, Bethesda, MD 20892 USA.
EM sleppla@niaid.nih.gov
FU National Institute of Allergy and Infectious Diseases; National
Institute of Diabetes and Digestive and Kidney Diseases; National Cancer
Institute, National Institutes of Health
FX Grant sponsor: Intramural research programs of the National Institute of
Allergy and Infectious Diseases, the National Institute of Diabetes and
Digestive and Kidney Diseases, and the National Cancer Institute,
National Institutes of Health.
NR 34
TC 5
Z9 5
U1 0
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0961-8368
EI 1469-896X
J9 PROTEIN SCI
JI Protein Sci.
PD NOV
PY 2015
VL 24
IS 11
BP 1808
EP 1819
DI 10.1002/pro.2773
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA CU7NK
UT WOS:000363727200011
PM 26271475
ER
PT J
AU Redd, AD
Newell, K
Patel, EU
Nalugoda, F
Ssebbowa, P
Kalibbala, S
Frank, MA
Tobian, AAR
Gray, RH
Quinn, TC
Serwadda, D
Reynolds, SJ
AF Redd, Andrew D.
Newell, Kevin
Patel, Eshan U.
Nalugoda, Fred
Ssebbowa, Paschal
Kalibbala, Sarah
Frank, Melanie A.
Tobian, Aaron A. R.
Gray, Ronald H.
Quinn, Thomas C.
Serwadda, David
Reynolds, Steven J.
TI Decreased monocyte activation with daily acyclovir use in HIV-1/HSV-2
coinfected women
SO SEXUALLY TRANSMITTED INFECTIONS
LA English
DT Article
ID SIMPLEX-VIRUS TYPE-2; PLACEBO-CONTROLLED TRIAL; DISEASE PROGRESSION;
CROSSOVER TRIAL; HIV-1; VALACYCLOVIR; TRANSMISSION; REPLICATION;
INFECTION; THERAPY
AB Objectives Several clinical trials have demonstrated that daily treatment of HIV-infected individuals with the antiherpes drug acyclovir slightly decreases HIV-1 viral load and slows disease progression. This study examines if this slowing in clinical progression is a direct cause of the decrease in viral load or an indirect effect of lower immune activation due to lower levels of herpetic reactivation.
Methods Women who participated in a randomised clinical trial of daily acyclovir use (n=301) were monitored every 6 months for changes in immune activation. Soluble CD14 (sCD14), a marker for monocyte activation, and C-reactive protein (CRP), a marker for general immune activation, were measured by ELISA.
Results Initial levels of sCD14 and CRP were not predictive of HIV disease progression when controlling for initial CD4+ cell count and HIV viral load. sCD14 levels, but not CRP, decreased in the acyclovir treatment arm at a significantly faster rate than the placebo group, which was independent of changes in HIV viral load and CD4+ cell count in a multivariant mixed-effects model (p=0.039). However, the magnitude of this decrease was relatively small with a total estimated decrease of sCD14 of 15% of initial levels.
Conclusions These data suggest that decreased monocyte activation may play a minor role in the ability of daily acyclovir use to slow HIV disease progression.
C1 [Redd, Andrew D.; Patel, Eshan U.; Frank, Melanie A.; Quinn, Thomas C.; Reynolds, Steven J.] NIAID, Div Intramural Res, NIH, Bethesda, MD 20892 USA.
[Redd, Andrew D.; Quinn, Thomas C.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA.
[Newell, Kevin] Leidos Biomed Res, Frederick Natl Lab Canc Res, Clin Res Directorate, Clin Monitoring Res Program, Frederick, MD USA.
[Nalugoda, Fred; Ssebbowa, Paschal; Kalibbala, Sarah; Serwadda, David] Rakai Hlth Sci Program, Entebbe, Uganda.
[Tobian, Aaron A. R.] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA.
[Gray, Ronald H.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Serwadda, David] Makerere Univ, Inst Publ Hlth, Kampala, Uganda.
RP Reynolds, SJ (reprint author), US Embassy, NIAID NIH ICER Program, POB 7007, Kampala, Uganda.
EM sjreynolds@niaid.nih.gov
OI Patel, Eshan/0000-0003-2174-5004
FU Intramural NIH HHS; NIAID NIH HHS [AI001040]
NR 14
TC 4
Z9 4
U1 0
U2 3
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 1368-4973
EI 1472-3263
J9 SEX TRANSM INFECT
JI Sex. Transm. Infect.
PD NOV
PY 2015
VL 91
IS 7
BP 485
EP 488
DI 10.1136/sextrans-2014-051867
PG 4
WC Infectious Diseases
SC Infectious Diseases
GA CU4CO
UT WOS:000363474100008
PM 25904747
ER
PT J
AU Abdelmohsen, K
Gorospe, M
AF Abdelmohsen, Kotb
Gorospe, Myriam
TI Noncoding RNA control of cellular senescence
SO WILEY INTERDISCIPLINARY REVIEWS-RNA
LA English
DT Review
ID ONCOGENE-INDUCED SENESCENCE; HUMAN-DIPLOID FIBROBLASTS; LUNG-CANCER
CELLS; REPLICATIVE SENESCENCE; TUMOR-GROWTH; CYCLE ARREST; STEM-CELLS;
MULTIPLE MICRORNAS; HUMAN TELOMERASE; PROSTATE-CANCER
AB Senescent cells accumulate in normal tissues with advancing age and arise by long-term culture of primary cells. Senescence develops following exposure to a range of stress-causing agents and broadly influences the physiology and pathology of tissues, organs, and systems in the body. While many proteins are known to control senescence, numerous noncoding (nc)RNAs are also found to promote or repress the senescent phenotype. Here, we review the regulatory ncRNAs (primarily microRNAs and lncRNAs) identified to-date as key modulators of senescence. We highlight the major senescent pathways (p53/p21 and pRB/p16), as well as the senescence-associated secretory phenotype (SASP) and other senescence-associated events governed by ncRNAs, and discuss the importance of understanding comprehensively the ncRNAs implicated in cell senescence. WIREs RNA 2015, 6:615-629. doi: 10.1002/wrna.1297 For further resources related to this article, please visit the .
C1 [Abdelmohsen, Kotb; Gorospe, Myriam] NIA, Genet Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
RP Abdelmohsen, K (reprint author), NIA, Genet Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
EM abdelmohsenk@mail.nih.gov; myriam-gor-ospe@nih.gov
FU NIA-IRP, NIH
FX This work was supported by the NIA-IRP, NIH.
NR 168
TC 8
Z9 8
U1 1
U2 11
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1757-7004
EI 1757-7012
J9 WIRES RNA
JI Wiley Interdiscip. Rev.-RNA
PD NOV-DEC
PY 2015
VL 6
IS 6
BP 615
EP 629
DI 10.1002/wrna.1297
PG 15
WC Cell Biology
SC Cell Biology
GA CU9NK
UT WOS:000363871000002
PM 26331977
ER
PT J
AU Huestis, MA
AF Huestis, Marilyn A.
TI Deterring driving under the influence of cannabis
SO ADDICTION
LA English
DT Editorial Material
DE Blood; cannabis; driving; driving under the influence; impairment;
marijuana; oral fluid
ID MARIJUANA; ALCOHOL; BLOOD; DRIVERS; CRASHES; DRUGS
C1 Natl Inst Drug Abuse, Natl Inst Hlth, Intramural Res Program, Chem & Drug Metab, Baltimore, MD 21235 USA.
RP Huestis, MA (reprint author), Natl Inst Drug Abuse, Natl Inst Hlth, Intramural Res Program, Chem & Drug Metab, Baltimore, MD 21235 USA.
EM mhuestis@intra.nida.nih.gov
NR 16
TC 2
Z9 2
U1 3
U2 14
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0965-2140
EI 1360-0443
J9 ADDICTION
JI Addiction
PD NOV
PY 2015
VL 110
IS 11
BP 1697
EP 1698
DI 10.1111/add.13041
PG 2
WC Substance Abuse; Psychiatry
SC Substance Abuse; Psychiatry
GA CU2CG
UT WOS:000363329100001
PM 26264558
ER
PT J
AU Cherpitel, CJ
Ye, Y
Bond, J
Borges, G
Monteiro, M
Chou, P
Hao, W
AF Cherpitel, Cheryl J.
Ye, Yu
Bond, Jason
Borges, Guilherme
Monteiro, Maristela
Chou, Patricia
Hao, Wei
TI Alcohol Attributable Fraction for Injury Morbidity from the
Dose-Response Relationship of Acute Alcohol Consumption: Emergency
Department Data from 18 Countries
SO ADDICTION
LA English
DT Article
DE Alcohol; alcohol attributable fraction; dose-response; emergency
department; gender; injury; motor vehicle; violence
ID CASE-CROSSOVER DESIGN; GENERAL-POPULATION; NONFATAL INJURIES;
RISK-FACTORS; RECALL BIAS; DRINKING; PATTERNS; DISEASE; BURDEN; ROOM
AB AimsTo calculate the alcohol-attributable fraction (AAF) of injury morbidity by volume of consumption prior to injury based on newly reported relative risk (RR) estimates.
DesignAAF estimates based on the dose-response RR estimates obtained from previous pair-matched case-crossover fractional polynomial analysis of mean volume in volume categories were calculated from the prevalence of drinking prior to injury in each volume category.
SettingThirty-seven emergency departments (EDs) across 18 countries.
ParticipantsProbability samples of patients, with equal representation of each shift for each day of the week, totaling 14,026 who arrived at the ED within six hours of injury from ED studies conducted between 2001 and 2011.
MeasurementsAAF was analyzed by gender, age (18-30; >30), cause of injury (traffic, assault, fall, other), and country detrimental drinking pattern (DDP).
FindingsFor the EDs analyzed, 16.4% of all injuries were estimated to be attributable to alcohol, and the AAF did not vary by age but was over twice as large for males (20.6%; 19.3-21.8) than for females (8.6%; 7.5-9.7%). While females were at greater risk of injury than males at higher volume levels, lower prevalence of women drinking at higher levels contributed to overall lower AAF for women. Assault-related injuries showed the largest AAF (44.1%; 37.6-42.6). AAF was slightly higher for injuries from falls (14.3%; 12.9-15.7) than motor vehicle crashes (11.1%; 9.3-12.9). AAF was higher in those countries with a DDP of 3 (18.6; 17.5-19.7) and 4 (19.4%; 17.3-21.6) than those with a DDP of 2 (12.0%; 10.5-13.5).
ConclusionsAlcohol-attributable injuries presenting in emergency departments are higher for males than females, for violence-related injuries compared with other types of injury, and for countries with more detrimental drinking patterns compared with those with less detrimental patterns.
C1 [Cherpitel, Cheryl J.; Ye, Yu; Bond, Jason] Alcohol Res Grp, Emeryville, CA 94608 USA.
[Borges, Guilherme] Univ Autonoma Metropolitana, Inst Nacl Psiquiatria, Mexico City, DF, Mexico.
[Monteiro, Maristela] Pan Amer Hlth Org, Washington, DC USA.
[Chou, Patricia] Natl Inst Alcohol Abuse & Alcoholism, Washington, DC USA.
[Hao, Wei] Hunan Med Univ, Changsha, Peoples R China.
RP Cherpitel, CJ (reprint author), Alcohol Res Grp, 6475 Christie Ave,Suite 400, Emeryville, CA 94608 USA.
EM ccherpitel@arg.org
OI Borges, Guilherme/0000-0002-3269-0507
FU World Health Organization; U.S. National Institute on Alcohol Abuse and
Alcoholism (NIAAA) [RO1 2 AA013750-04]
FX The paper is based, in part on data collected by the following
collaborators participating in the Emergency Room Collaborative Alcohol
Analysis Project (ERCAAP) (C. J. Cherpitel, P.I., USA): W. Cook (USA),
G. Gmel (Switzerland), A. Hope (Ireland); and collaborators
participating in the WHO Collaborative Study on Alcohol and Injuries,
sponsored by the World Health Organization and implemented by the WHO
Collaborative Study Group on Alcohol and Injuries under the direction of
V. Poznyak and M. Peden (WHO, Switzerland): V. Benegal (India); G.
Borges (Mexico); S. Casswell (New Zealand); M. Cremonte (Argentina); R.
Evsegneev (Belarus); N. Figlie and R. Larajeira (Brazil); N. Giesbrecht
and S. Macdonald (Canada); W. Hao (China); S. Larsson and M. Stafstrom
(Sweden); H. Sovinova (Czech Republic. A list of other staff
contributing to the project can be found in the Main Report of the
Collaborative Study on Alcohol and Injuries, WHO, Geneva.; Supported by
a grant from the U.S. National Institute on Alcohol Abuse and Alcoholism
(NIAAA) (RO1 2 AA013750-04)
NR 38
TC 9
Z9 9
U1 1
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0965-2140
EI 1360-0443
J9 ADDICTION
JI Addiction
PD NOV
PY 2015
VL 110
IS 11
BP 1724
EP 1732
DI 10.1111/add.13031
PG 9
WC Substance Abuse; Psychiatry
SC Substance Abuse; Psychiatry
GA CU2CG
UT WOS:000363329100009
PM 26119350
ER
PT J
AU Addissie, YA
Kotecha, U
Hart, RA
Martinez, AF
Kruszka, P
Muenke, M
AF Addissie, Yonit A.
Kotecha, Udhaya
Hart, Rachel A.
Martinez, Ariel F.
Kruszka, Paul
Muenke, Maximilian
TI Craniosynostosis and Noonan syndrome with KRAS mutations: Expanding the
phenotype with a case report and review of the literature
SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A
LA English
DT Article
DE Noonan syndrome; KRAS; craniosynostosis; RAS-MAPK; RASopathy
ID RAS/MAPK SIGNALING PATHWAY; FACIO-CUTANEOUS SYNDROME; LOOSE ANAGEN HAIR;
GERMLINE KRAS; HYPERTROPHIC CARDIOMYOPATHY; DEVELOPMENTAL DISORDERS;
COSTELLO-SYNDROME; BRAF MUTATIONS; GENE; PROTEIN
AB Noonan syndrome (NS) is a multiple congenital anomaly syndrome caused by germline mutations in genes coding for components of the Ras-mitogen-activated protein kinase (RAS-MAPK) pathway. Features include short stature, characteristic facies, congenital heart anomalies, and developmental delay. While there is considerable clinical heterogeneity in NS, craniosynostosis is not a common feature of the condition. Here, we report on a 2 month-old girl with Noonan syndrome associated with a de novo mutation in KRAS (p.P34Q) and premature closure of the sagittal suture. We provide a review of the literature of germline KRAS mutations and find that approximately 10% of published cases have craniosynostosis. Our findings expand on the NS phenotype and suggest that germline mutations in the KRAS gene are causally involved in craniosynostosis, supporting the role of the RAS-MAPK pathway as a mediator of aberrant bone growth in cranial sutures. The inclusion of craniosynostosis as a possible phenotype in KRAS-associated Noonan Syndrome has implications in the differential diagnosis and surgical management of individuals with craniosynostosis. (c) 2015 Wiley Periodicals, Inc.
C1 [Addissie, Yonit A.; Hart, Rachel A.; Martinez, Ariel F.; Kruszka, Paul; Muenke, Maximilian] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA.
[Kotecha, Udhaya] Sir Ganga Ram Hosp, Ctr Med Genet, New Delhi, India.
RP Kruszka, P (reprint author), NHGRI, Med Genet Branch, NIH, 35 Convent Dr, Bethesda, MD 20892 USA.
EM paul.kruszka@nih.gov
FU Division of Intramural Research of the National Human Genome Research
Institute
FX Grant sponsor: Division of Intramural Research of the National Human
Genome Research Institute.
NR 56
TC 5
Z9 5
U1 1
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1552-4825
EI 1552-4833
J9 AM J MED GENET A
JI Am. J. Med. Genet. A
PD NOV
PY 2015
VL 167
IS 11
BP 2657
EP 2663
DI 10.1002/ajmg.a.37259
PG 7
WC Genetics & Heredity
SC Genetics & Heredity
GA CU1LB
UT WOS:000363281900027
PM 26249544
ER
PT J
AU Weiss, K
Applegate, C
Wang, T
Batista, DAS
AF Weiss, Karin
Applegate, Carolyn
Wang, Tao
Batista, Denise A. S.
TI Familial TAB2 microdeletion and congenital heart defects including
unusual valve dysplasia and tetralogy of fallot
SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A
LA English
DT Article
DE cardiac outflow tract; congenital heart defect; deletion 6q; myxomatous
cardiac valves; TAB2
ID GROWTH FAILURE; DISEASE; DELETION
AB Haploinsufficiency of TAB2 was recently implicated as a cause for a variety of congenital heart defects. Reported cases have genomic deletions of 2-10Mbs including TAB2 at 6q24-25 are almost always de novo and show variable cardiac and extra cardiac phenotype. We report on an inherited, 281kb deletion in a three generation family. This is the smallest reported deletion involving TAB2 that segregates with congenital heart defects. Three affected individuals in this family present with myxomatous cardiac valves in addition to structural heart defects commonly associated with TAB2 deletions. Findings from this family support a key role of TAB2 haploinsufficiency in congenital heart defects and expand the phenotypic spectrum of TAB2-microdeletion syndrome. (c) 2015 Wiley Periodicals, Inc.
C1 [Weiss, Karin] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA.
[Applegate, Carolyn; Wang, Tao; Batista, Denise A. S.] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD 21287 USA.
[Wang, Tao] Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21287 USA.
[Batista, Denise A. S.] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21287 USA.
[Batista, Denise A. S.] Kennedy Krieger Inst, Cytogenet & Microarray Lab, Baltimore, MD USA.
RP Batista, DAS (reprint author), Johns Hopkins Univ, Cytogenet Lab, 600 N Wolfe St,Pk Bldg SB 202, Baltimore, MD 21287 USA.
EM dbatist1@jhmi.edu
NR 21
TC 2
Z9 2
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1552-4825
EI 1552-4833
J9 AM J MED GENET A
JI Am. J. Med. Genet. A
PD NOV
PY 2015
VL 167
IS 11
BP 2702
EP 2706
DI 10.1002/ajmg.a.37210
PG 5
WC Genetics & Heredity
SC Genetics & Heredity
GA CU1LB
UT WOS:000363281900034
PM 26139517
ER
PT J
AU Burgemeister, AL
Zirn, B
Oeffner, F
Kaler, SG
Lemm, G
Rossier, E
Buttel, HM
AF Burgemeister, Anna Lena
Zirn, Birgit
Oeffner, Frank
Kaler, Stephen G.
Lemm, Gunther
Rossier, Eva
Buettel, Hans-Martin
TI Menkes disease with discordant phenotype in female monozygotic twins
SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A
LA English
DT Article
DE Menkes disease; female monozygotic twins; discordant phenotype; ATP7A
ID MUSCULAR-DYSTROPHY; GROWTH
AB Menkes disease (MD) is a rare X-linked recessive disorder caused by mutations in the ATP7A gene. This neurodegenerative disorder typically affects males and is characterized by impaired copper distribution and the malfunction of several copper-dependent enzymes. We report clinically discordant female monozygotic twins (MZT) with a heterozygous ATP7A mutation. One twin girl is healthy at the current age of 4 years, whereas the other twin girl developed classical MD, showed disease stabilization under copper histidine treatment but died at the age of 3 years. Presumably, the affected girl developed MD due to skewed X inactivation, although this could not be demonstrated in two tissues (blood, buccal mucosa). This case is a rare example of an affected girl with MD and shows the possibility of a discordant phenotype in MZT girls. As speculated in other X-linked diseases, the process of monozygotic twinning may be associated with skewed X inactivation leading to a discordant phenotype. (c) 2015 Wiley Periodicals, Inc.
C1 [Burgemeister, Anna Lena; Zirn, Birgit; Oeffner, Frank; Rossier, Eva] Genetikum, Genet Counseling & Diagnost, D-70174 Stuttgart, Germany.
[Burgemeister, Anna Lena; Zirn, Birgit; Oeffner, Frank; Rossier, Eva] Genetikum, Genet Counseling & Diagnost, Neu Ulm, Germany.
[Zirn, Birgit] Univ Med, Dept Pediat & Neuropediat, Gottingen, Germany.
[Kaler, Stephen G.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Translat Neurosci, Program Mol Med, NIH, Bethesda, MD USA.
[Lemm, Gunther] SLK Klinikum, Dept Radiol, Heilbronn, Germany.
[Buettel, Hans-Martin] SLK Klinikum, Dept Pediat & Neuropediat, Heilbronn, Germany.
RP Burgemeister, AL (reprint author), Genetikum, Genet Counseling & Diagnost, Buchsenstr 20, D-70174 Stuttgart, Germany.
EM burgemeister@genetikum.de
NR 20
TC 0
Z9 1
U1 0
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1552-4825
EI 1552-4833
J9 AM J MED GENET A
JI Am. J. Med. Genet. A
PD NOV
PY 2015
VL 167
IS 11
BP 2826
EP 2829
DI 10.1002/ajmg.a.37276
PG 4
WC Genetics & Heredity
SC Genetics & Heredity
GA CU1LB
UT WOS:000363281900054
PM 26239182
ER
PT J
AU Taylor, CL
Thomas, PR
Aloia, JF
Millard, PS
Rosen, CJ
AF Taylor, Christine L.
Thomas, Paul R.
Aloia, John F.
Millard, Peter S.
Rosen, Clifford J.
TI Questions About Vitamin D for Primary Care Practice: Input From an NIH
Conference
SO AMERICAN JOURNAL OF MEDICINE
LA English
DT Review
DE 25-hydroxyvitamin D; 25(OH)D; Laboratory testing; Screening;
Supplementation; Vitamin D; Vitamin D status
ID CLINICAL-PRACTICE; D DEFICIENCY
AB There is considerable consumer and physician interest in vitamin D as a possible therapeutic agent for a range of clinical conditions and, despite mixed evidence, the interest does not appear to lessen. Some clinicians believe that consumption of vitaminD is inadequate and, in turn, advocate vitamin D supplementation to increase serum levels of the nutrient. However, evidence concerning the role of vitamin D in health and disease is conflicting, and primary care physicians have little time to sort through the data and may find it difficult to advise their patients. To better understand the challenges that primary care physicians face regarding vitamin D, and to help inform those who provide guidance for clinical decision-making, the Office of Dietary Supplements at the National Institutes of Health, with co-sponsorship from other federal health agencies, held a conference titled Vitamin D: Moving Toward Evidence-based Decision Making in Primary Care in December 2014. More than 20 invited presenters and panelists considered laboratory methods for measuring vitamin D status, discussed how clinical studies of vitamin D should be evaluated and used in developing recommendations, noted the role of values and preferences in clinical decision-making, debated the current science related to at-risk groups, and described emerging data about health risks of excessive intakes of vitamin D. Eight questions about vitamin D stem from the Conference presentations as well as other expert sources. Published by Elsevier Inc.
C1 [Taylor, Christine L.; Thomas, Paul R.] NIH, Off Dietary Supplements, Bethesda, MD 20892 USA.
[Aloia, John F.] Winthrop Univ Hosp, Bone Mineral Res Ctr, Mineola, NY 11501 USA.
[Millard, Peter S.] Seaport Community Hlth Ctr, Belfast, ME USA.
[Rosen, Clifford J.] Maine Med Ctr, Res Inst, Ctr Clin & Translat Res, Scarborough, ME USA.
RP Taylor, CL (reprint author), NIH, Off Dietary Supplements, 6100 Execut Blvd,Room 3B01,MSC 7517, Bethesda, MD 20892 USA.
EM TaylorCL3@od.nih.gov
FU National Center for Complementary and Integrative Health; NCCIH;
National Institute of Arthritis and Musculoskeletal and Skin Diseases
(NIAMS); National Institute of Diabetes and Digestive and Kidney
Diseases (NIDDK); National Institute on Aging (NIA); Agency for
Healthcare Research and Quality (AHRQ); Division for Heart Health and
Stroke Prevention of the Centers for Disease Control and Prevention
(CDC); National Institute of Standards and Technology (NIST); Office of
Disease Prevention and Health Promotion (ODPHP) at the Department of
Health and Human Services; US Food and Drug Administration
FX This review was prepared from a conference held at the National
Institutes of Health (NIH) on December 2-3, 2014 titled "Vitamin D:
Moving Toward Evidence-based Decision Making in Primary Care." At the
NIH, the primary sponsor was the Office of Dietary Supplements, with
co-sponsorship by the National Center for Complementary and Alternative
Medicine (now the National Center for Complementary and Integrative
Health; NCCIH), National Institute of Arthritis and Musculoskeletal and
Skin Diseases (NIAMS), National Institute of Diabetes and Digestive and
Kidney Diseases (NIDDK), and the National Institute on Aging (NIA).
Additional co-sponsorship was provided by the Agency for Healthcare
Research and Quality (AHRQ), Division for Heart Health and Stroke
Prevention of the Centers for Disease Control and Prevention (CDC),
National Institute of Standards and Technology (NIST), Office of Disease
Prevention and Health Promotion (ODPHP) at the Department of Health and
Human Services, and the US Food and Drug Administration.
NR 9
TC 0
Z9 0
U1 1
U2 10
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9343
EI 1555-7162
J9 AM J MED
JI Am. J. Med.
PD NOV
PY 2015
VL 128
IS 11
BP 1167
EP 1170
DI 10.1016/j.amjmed.2015.05.025
PG 4
WC Medicine, General & Internal
SC General & Internal Medicine
GA CU3VI
UT WOS:000363453500027
PM 26071820
ER
PT J
AU Dettmer, AM
Hambright, MK
Novak, MF
AF Dettmer, A. M.
Hambright, M. K.
Novak, M. F.
TI ASP EDUCATION COMMITTEE PRE-CONFERENCE EDUCATIONAL OUTREACH
SO AMERICAN JOURNAL OF PRIMATOLOGY
LA English
DT Meeting Abstract
CT 38th Annual Meeting of the American-Society-of-Primatologists
CY JUN 18-21, 2015
CL Bend, OR
SP Amer Soc Primatologists, Chimps Inc, Primate Conservat Inc, Purina LabDiet, Res Diets Inc, Carter 2 Syst Inc, S Karger Publishers Inc, Cambridge Univ Press, Unifab Corp, Van Hoang Dao
C1 [Dettmer, A. M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Lab Comparat Ethol, NIH, Poolesville, MD 20837 USA.
[Hambright, M. K.] Coll Coastal Georgia, Brunswick, GA USA.
[Novak, M. F.] Cent Oregon Community Coll, Bend, OR USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0275-2565
EI 1098-2345
J9 AM J PRIMATOL
JI Am. J. Primatol.
PD NOV
PY 2015
VL 77
SU 1
MA 3
BP 37
EP 37
PG 1
WC Zoology
SC Zoology
GA CU5GQ
UT WOS:000363560500003
ER
PT J
AU Dettmer, AM
Woodward, RA
Rosenberg, K
Suomi, SJ
Novak, MA
Meyer, JS
AF Dettmer, A. M.
Woodward, R. A.
Rosenberg, K.
Suomi, S. J.
Novak, M. A.
Meyer, J. S.
TI HAIR CORTISOL IS ASSOCIATED WITH CHANGES IN HAIR LOSS AND BODY CONDITION
ACROSS PUBERTY IN MALE RHESUS MONKEYS
SO AMERICAN JOURNAL OF PRIMATOLOGY
LA English
DT Meeting Abstract
CT 38th Annual Meeting of the American-Society-of-Primatologists
CY JUN 18-21, 2015
CL Bend, OR
SP Amer Soc Primatologists, Chimps Inc, Primate Conservat Inc, Purina LabDiet, Res Diets Inc, Carter 2 Syst Inc, S Karger Publishers Inc, Cambridge Univ Press, Unifab Corp, Van Hoang Dao
C1 [Dettmer, A. M.; Suomi, S. J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Lab Comparat Ethol, NIH, Poolesville, MD 20837 USA.
[Woodward, R. A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Res Anim Management Branch, Div Intramural Res, NIH, Poolesville, MD 20837 USA.
[Rosenberg, K.; Novak, M. A.; Meyer, J. S.] Univ Massachusetts, Dept Psychol, Amherst, MA 01003 USA.
NR 0
TC 0
Z9 0
U1 3
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0275-2565
EI 1098-2345
J9 AM J PRIMATOL
JI Am. J. Primatol.
PD NOV
PY 2015
VL 77
SU 1
MA 37
BP 46
EP 46
PG 1
WC Zoology
SC Zoology
GA CU5GQ
UT WOS:000363560500020
ER
PT J
AU Hamel, AF
Dettmer, AM
Miller, MM
Suomi, SJ
Meyer, JS
Novak, MA
AF Hamel, A. F.
Dettmer, A. M.
Miller, M. M.
Suomi, S. J.
Meyer, J. S.
Novak, M. A.
TI EARLY REARING EXPERIENCE MODULATES TEMPERAMENT AND ACTIVITY OF THE
OXYTOCIN SYSTEM AND HYPOTHALAMIC-PITUITARY-ADRENOCORTICAL (HPA) AXIS IN
INFANT RHESUS MONKEYS (MACACA MULATTA)
SO AMERICAN JOURNAL OF PRIMATOLOGY
LA English
DT Meeting Abstract
CT 38th Annual Meeting of the American-Society-of-Primatologists
CY JUN 18-21, 2015
CL Bend, OR
SP Amer Soc Primatologists, Chimps Inc, Primate Conservat Inc, Purina LabDiet, Res Diets Inc, Carter 2 Syst Inc, S Karger Publishers Inc, Cambridge Univ Press, Unifab Corp, Van Hoang Dao
C1 [Hamel, A. F.] Univ Massachusetts, Neurosci & Behav Grad Program, Amherst, MA 01003 USA.
[Dettmer, A. M.; Miller, M. M.; Suomi, S. J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Comparat Ethol Lab, NIH, Poolesville, MD USA.
[Meyer, J. S.; Novak, M. A.] Univ Massachusetts, Psychol & Brain Sci, Amherst, MA 01003 USA.
NR 0
TC 0
Z9 0
U1 2
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0275-2565
EI 1098-2345
J9 AM J PRIMATOL
JI Am. J. Primatol.
PD NOV
PY 2015
VL 77
SU 1
MA 53
BP 53
EP 54
PG 2
WC Zoology
SC Zoology
GA CU5GQ
UT WOS:000363560500035
ER
PT J
AU Aston, SA
O'Connell, PH
Schwandt, ML
Barr, CS
Lindell, SG
Suomi, SJ
Higley, JD
AF Aston, S. A.
O'Connell, P. H.
Schwandt, M. L.
Barr, C. S.
Lindell, S. G.
Suomi, S. J.
Higley, J. D.
TI A C-TO-T SNP IN THE PROMOTER REGION OF THE RHESUS MACAQUE (MACACA
MULATTA) CRH GENE INTERACTS WITH EARLY REARING EXPERIENCES INFLUENCING
ANXIOUS BEHAVIOR
SO AMERICAN JOURNAL OF PRIMATOLOGY
LA English
DT Meeting Abstract
CT 38th Annual Meeting of the American-Society-of-Primatologists
CY JUN 18-21, 2015
CL Bend, OR
SP Amer Soc Primatologists, Chimps Inc, Primate Conservat Inc, Purina LabDiet, Res Diets Inc, Carter 2 Syst Inc, S Karger Publishers Inc, Cambridge Univ Press, Unifab Corp, Van Hoang Dao
C1 [Aston, S. A.; O'Connell, P. H.; Higley, J. D.] Brigham Young Univ, Dept Psychol, SWKT 1042, Provo, UT 84602 USA.
[Schwandt, M. L.; Barr, C. S.; Lindell, S. G.; Suomi, S. J.] NIAAA, NIH, NICHD, New York, NY USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0275-2565
EI 1098-2345
J9 AM J PRIMATOL
JI Am. J. Primatol.
PD NOV
PY 2015
VL 77
SU 1
MA 66
BP 60
EP 60
PG 1
WC Zoology
SC Zoology
GA CU5GQ
UT WOS:000363560500048
ER
PT J
AU Peterson, EJ
Worlein, JM
Lee, GH
Dettmer, AM
Varner, EK
Novak, MA
AF Peterson, E. J.
Worlein, J. M.
Lee, G. H.
Dettmer, A. M.
Varner, E. K.
Novak, M. A.
TI LABORATORY HOUSED RHESUS MACAQUES (MACACA MULATTA) WITH SELF INJURIOUS
BEHAVIOR SHOW A BLUNTED BEHAVIORAL RESPONSE TO THE HUMAN INTRUDER TEST
SO AMERICAN JOURNAL OF PRIMATOLOGY
LA English
DT Meeting Abstract
CT 38th Annual Meeting of the American-Society-of-Primatologists
CY JUN 18-21, 2015
CL Bend, OR
SP Amer Soc Primatologists, Chimps Inc, Primate Conservat Inc, Purina LabDiet, Res Diets Inc, Carter 2 Syst Inc, S Karger Publishers Inc, Cambridge Univ Press, Unifab Corp, Van Hoang Dao
C1 [Peterson, E. J.] Univ Massachusetts, Neurosci & Behav Grad Program, Amherst, MA 01003 USA.
[Worlein, J. M.; Lee, G. H.] Washington Natl Primate Res Ctr, Seattle, WA USA.
[Varner, E. K.; Novak, M. A.] Univ Massachusetts, Psychol & Brain Sci, Amherst, MA 01003 USA.
[Dettmer, A. M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Lab Comparat Ethol, NIH, Poolesville, MD USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0275-2565
EI 1098-2345
J9 AM J PRIMATOL
JI Am. J. Primatol.
PD NOV
PY 2015
VL 77
SU 1
MA 92
BP 73
EP 74
PG 2
WC Zoology
SC Zoology
GA CU5GQ
UT WOS:000363560500074
ER
PT J
AU Paukner, A
Simpson, EA
Ferrari, PF
Suomi, SJ
AF Paukner, A.
Simpson, E. A.
Ferrari, P. F.
Suomi, S. J.
TI FACE-TO-FACE INTERACTIONS INCREASE SOCIAL VIEWING PREFERENCES IN INFANT
RHESUS MACAQUES (MACACA MULATTA)
SO AMERICAN JOURNAL OF PRIMATOLOGY
LA English
DT Meeting Abstract
CT 38th Annual Meeting of the American-Society-of-Primatologists
CY JUN 18-21, 2015
CL Bend, OR
SP Amer Soc Primatologists, Chimps Inc, Primate Conservat Inc, Purina LabDiet, Res Diets Inc, Carter 2 Syst Inc, S Karger Publishers Inc, Cambridge Univ Press, Unifab Corp, Van Hoang Dao
C1 [Paukner, A.; Simpson, E. A.; Suomi, S. J.] NIH, Lab Comparat Ethol, Anim Ctr, Poolesville, MD 20837 USA.
[Simpson, E. A.; Ferrari, P. F.] Univ Parma, I-43100 Parma, Italy.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0275-2565
EI 1098-2345
J9 AM J PRIMATOL
JI Am. J. Primatol.
PD NOV
PY 2015
VL 77
SU 1
MA 161
BP 104
EP 104
PG 1
WC Zoology
SC Zoology
GA CU5GQ
UT WOS:000363560500131
ER
PT J
AU Madrid, JE
Mandalaywala, TM
Coyne, SP
Garner, JP
Barr, CS
Maestripieri, D
Parker, KJ
AF Madrid, J. E.
Mandalaywala, T. M.
Coyne, S. P.
Garner, J. P.
Barr, C. S.
Maestripieri, D.
Parker, K. J.
TI SEROTONIN TRANSPORTER AND MATERNAL CARE: A SEX-SPECIFIC G X E EFFECT ON
JUVENILE SOCIAL PLAY IN FREE-RANGING RHESUS MACAQUES OF CAYO SANTIAGO
SO AMERICAN JOURNAL OF PRIMATOLOGY
LA English
DT Meeting Abstract
CT 38th Annual Meeting of the American-Society-of-Primatologists
CY JUN 18-21, 2015
CL Bend, OR
SP Amer Soc Primatologists, Chimps Inc, Primate Conservat Inc, Purina LabDiet, Res Diets Inc, Carter 2 Syst Inc, S Karger Publishers Inc, Cambridge Univ Press, Unifab Corp, Van Hoang Dao
C1 [Madrid, J. E.; Garner, J. P.; Parker, K. J.] Stanford Univ, MSLS, Stanford, CA 94305 USA.
[Mandalaywala, T. M.; Coyne, S. P.; Maestripieri, D.] Univ Chicago, Chicago, IL 60637 USA.
[Barr, C. S.] Natl Inst Hlth, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 4
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0275-2565
EI 1098-2345
J9 AM J PRIMATOL
JI Am. J. Primatol.
PD NOV
PY 2015
VL 77
SU 1
MA 169
BP 107
EP 108
PG 2
WC Zoology
SC Zoology
GA CU5GQ
UT WOS:000363560500138
ER
PT J
AU Hutchinson, EK
AF Hutchinson, E. K.
TI A REVIEW OF DRUG THERAPIES FOR SELF-INJURIOUS BEHAVIOR
SO AMERICAN JOURNAL OF PRIMATOLOGY
LA English
DT Meeting Abstract
CT 38th Annual Meeting of the American-Society-of-Primatologists
CY JUN 18-21, 2015
CL Bend, OR
SP Amer Soc Primatologists, Chimps Inc, Primate Conservat Inc, Purina LabDiet, Res Diets Inc, Carter 2 Syst Inc, S Karger Publishers Inc, Cambridge Univ Press, Unifab Corp, Van Hoang Dao
C1 [Hutchinson, E. K.] NIH, Div Vet Resources, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0275-2565
EI 1098-2345
J9 AM J PRIMATOL
JI Am. J. Primatol.
PD NOV
PY 2015
VL 77
SU 1
MA 170
BP 108
EP 108
PG 1
WC Zoology
SC Zoology
GA CU5GQ
UT WOS:000363560500139
ER
PT J
AU Giubellino, A
Lara, K
Martucci, V
Huynh, T
Agarwal, P
Pacak, K
Merino, MJ
AF Giubellino, Alessio
Lara, Karlena
Martucci, Victoria
Than Huynh
Agarwal, Piyush
Pacak, Karel
Merino, Maria J.
TI Urinary Bladder Paragangliomas How Immunohistochemistry Can Assist to
Identify Patients With SDHB Germline and Somatic Mutations
SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY
LA English
DT Article
DE bladder paraganglioma; SDHB; somatic mutation
ID PHEOCHROMOCYTOMA; SPECIMENS; NEOPLASMS
AB Urinary bladder paraganglioma (paraganglioma) is a rare tumor of chromaffin cells of the sympathetic system of the urinary bladder wall. We studied 14 cases of this entity and investigated the usefulness of SDHB protein staining by immunohistochemistry (IHC) as a diagnostic tool to identify patients with bladder paragangliomas that could be associated with SDHB gene mutations, as these patients have a more aggressive disease. Eleven tumors from these patients were stained by IHC. Six of 11 tumors were negative for SDHB staining by IHC with no cytoplasmic staining in tumor cells when compared with normal tissues. Five of these 6 negative cases were confirmed to be positive for germline SDHB mutations. One case showed negative staining and no germline SDHB mutation; however, further investigation of the tumor revealed a somatic SDHB gene deletion. The remaining 5 cases showed strong cytoplasmic staining, but they were negative for the presence of SDHB mutation. They were found to be either sporadic tumors or part of von Hippel-Lindau syndrome. Staining for SDHA was positive in all cases. Our study confirms that there is very good correlation between the presence of an SDHB mutation, whether germline or sporadic, and negative SDHB IHC staining in urinary bladder paragangliomas, and this is the first study to demonstrate that somatic mutations can be recognized by IHC staining.
C1 [Giubellino, Alessio; Lara, Karlena; Merino, Maria J.] NCI, Translat Surg Pathol Sect, Pathol Lab, Bethesda, MD 20892 USA.
[Martucci, Victoria; Than Huynh; Pacak, Karel] NICHHD, Bethesda, MD 20892 USA.
[Agarwal, Piyush] NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA.
RP Giubellino, A (reprint author), NCI, 10 Ctr Dr,Bldg 10,Room 2B38, Bethesda, MD 20892 USA.
EM giubella@mail.nih.gov
FU Intramural NIH HHS [Z99 CA999999]
NR 14
TC 3
Z9 3
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0147-5185
EI 1532-0979
J9 AM J SURG PATHOL
JI Am. J. Surg. Pathol.
PD NOV
PY 2015
VL 39
IS 11
BP 1488
EP 1492
DI 10.1097/PAS.0000000000000534
PG 5
WC Pathology; Surgery
SC Pathology; Surgery
GA CU2TH
UT WOS:000363375900005
PM 26457353
ER
PT J
AU Blau, JE
Abegg, MR
Flegel, WA
Zhao, X
Harlan, DM
Rother, KI
AF Blau, J. E.
Abegg, M. R.
Flegel, W. A.
Zhao, X.
Harlan, D. M.
Rother, K. I.
TI Long-Term Immunosuppression After Solitary Islet Transplantation Is
Associated With Preserved C-Peptide Secretion for More Than a Decade
SO AMERICAN JOURNAL OF TRANSPLANTATION
LA English
DT Article
ID INTENSIVE MEDICAL THERAPY; 5-YEAR FOLLOW-UP; QUALITY-OF-LIFE;
INSULIN-INDEPENDENCE; CELL TRANSPLANTATION; HLA ANTIBODIES; TYPE-1;
PROGRESSION; RECIPIENTS
AB We report on two patients with type 1 diabetes (T1D) after solitary islet transplantation in 2001. They received steroid-sparing immunosuppression (daclizumab, sirolimus, and tacrolimus according to the Edmonton protocol). Both patients became insulin independent for 2 years: Patient A, a 42-year-old female with a 12-year history of T1D, received two islet infusions; patient B, a 53-year-old female with a 40-year T1D history, received one islet infusion. Pretransplant, both had undetectable C-peptide concentrations and frequent and severe hypoglycemia. Pretransplant, hemoglobin A1c (HbA1c) was 7.8% and 8.8% and insulin requirements were 0.47 and 0.33units/kg/day, respectively. Posttransplant, C-peptide levels remained detectable while immunosuppression was continued, but decreased over time. Insulin was re-started 2 years posttransplant in both patients. Since patient A's glycemia and insulin requirements trended toward pretransplant levels, immunosuppression was discontinued after 13 years. This resulted in a sudden cessation of C-peptide secretion. Patient B continues on immunosuppression, has better HbA1c, and half the insulin requirement compared to pretransplant. Both patients no longer experience severe hypoglycemia. Herein, we document blood glucose concentrations over time (>30000 measurements per patient) and cell function based on C-peptide secretion. Despite renewed insulin dependence, both patients express satisfaction with having undergone the procedure.
C1 [Blau, J. E.; Abegg, M. R.; Zhao, X.; Rother, K. I.] NIDDK, Diabet Endocrinol & Obes Branch, NIH, Bethesda, MD 20892 USA.
[Flegel, W. A.] NIH, Dept Transfus Med, NIH Clin Ctr, Bethesda, MD 20892 USA.
[Harlan, D. M.] Univ Massachusetts, Sch Med, Dept Internal Med, Div Diabet Endocrinol & Nutr,Diabet Ctr Excellenc, North Worcester, MA USA.
RP Rother, KI (reprint author), NIDDK, Diabet Endocrinol & Obes Branch, NIH, Bethesda, MD 20892 USA.
EM kristina.rother@nih.gov
FU Intramural Research Program of the NIH Clinical Center
FX We would like to thank Sharon D. Adams, from the Department of
Transfusion Medicine, NIH Clinical Center, for HLA testing. This work
was supported by the Intramural Research Program of the NIH Clinical
Center.
NR 24
TC 2
Z9 2
U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1600-6135
EI 1600-6143
J9 AM J TRANSPLANT
JI Am. J. Transplant.
PD NOV
PY 2015
VL 15
IS 11
BP 2995
EP 3001
DI 10.1111/ajt.13383
PG 7
WC Surgery; Transplantation
SC Surgery; Transplantation
GA CU1FG
UT WOS:000363264800025
PM 26184712
ER
PT J
AU Marcum, ZA
Perera, S
Thorpe, JM
Switzer, GE
Gray, SL
Castle, NG
Strotmeyer, ES
Simonsick, EM
Bauer, DC
Shorr, RI
Studenski, SA
Hanlon, JT
AF Marcum, Zachary A.
Perera, Subashan
Thorpe, Joshua M.
Switzer, Galen E.
Gray, Shelly L.
Castle, Nicholas G.
Strotmeyer, Elsa S.
Simonsick, Eleanor M.
Bauer, Douglas C.
Shorr, Ronald I.
Studenski, Stephanie A.
Hanlon, Joseph T.
CA Hlth ABC Study USA
TI Anticholinergic Use and Recurrent Falls in Community-Dwelling Older
Adults: Findings From the Health ABC Study
SO ANNALS OF PHARMACOTHERAPY
LA English
DT Article
DE cholinergic antagonist; accidental falls; older adults;
pharmacoepidemiology
ID BODY-COMPOSITION; PEOPLE; COHORT; ASSOCIATIONS; MEDICATIONS; BURDEN;
ELDERS; RISK; CARE
AB Background: Although it is generally accepted that anticholinergic use may lead to a fall, results from studies assessing the association between anticholinergic use and falls are mixed. In addition, direct evidence of an association between use of anticholinergic medications and recurrent falls among community-dwelling elders is not available. Objective: To assess the association between anticholinergic use across multiple anticholinergic subclasses, including over-the-counter medications, and recurrent falls. Methods: This was a longitudinal analysis of 2948 participants, with data collected via interview at year 1 from the Health, Aging and Body Composition study and followed through year 7 (1997-2004). Self-reported use of anticholinergic medication was identified at years 1, 2, 3, 5, and 6 as defined by the list from the 2015 American Geriatrics Society Beers Criteria. Dosage and duration were also examined. The main outcome was recurrent falls (2) in an ensuing 12-month period from each medication data collection. Results: Using multivariable generalized estimating equation models, controlling for demographic, health status/behaviors, and access-to-care factors, a 34% increase in likelihood of recurrent falls in anticholinergic users (adjusted odds ratio = 1.34; 95% CI = 0.93-1.93) was observed, but the results were not statistically significant; similar results were found with higher doses and longer duration of use. Conclusion: Increased point estimates suggest an association of anticholinergic use with recurrent falls, but the associations did not reach statistical significance. Future studies are needed for more definitive evidence and to examine other measures of anticholinergic burden and associations with more intermediate adverse effects such as cognitive function.
C1 [Marcum, Zachary A.; Gray, Shelly L.] Univ Washington, Seattle, WA 98102 USA.
[Perera, Subashan; Thorpe, Joshua M.; Switzer, Galen E.; Castle, Nicholas G.; Strotmeyer, Elsa S.; Hanlon, Joseph T.] Univ Pittsburgh, Pittsburgh, PA USA.
[Thorpe, Joshua M.; Switzer, Galen E.; Hanlon, Joseph T.] VA Pittsburgh Healthcare Syst, Pittsburgh, PA USA.
[Simonsick, Eleanor M.; Studenski, Stephanie A.] NIA, Baltimore, MD 21224 USA.
[Bauer, Douglas C.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Shorr, Ronald I.] Vet Affairs Med Ctr, Gainesville, FL 32608 USA.
RP Marcum, ZA (reprint author), Univ Washington, Sch Pharm, Dept Pharm, 1959 NE Pacific St,H375G,Box 357630, Seattle, WA 98102 USA.
EM zmarcum@uw.edu
OI Strotmeyer, Elsa/0000-0002-4093-6036
FU National Institute on Aging (NIA) [P30AG024827, T32 AG021885,
K07AG033174, R01AG028050]; National Institutes of Health, NIA
[N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106]; National Institute of
Nursing research grant [R01NR012459]
FX The authors disclosed receipt of the following financial support for the
research, authorship, and/or publication of this article: This research
was primarily supported by National Institute on Aging (NIA) grants and
contracts (P30AG024827, T32 AG021885, K07AG033174, R01AG028050). This
research was also supported in part by the Intramural Research program
of the National Institutes of Health, NIA (N01-AG-6-2101, N01-AG-6-2103,
and N01-AG-6-2106), and a National Institute of Nursing research grant
(R01NR012459).
NR 29
TC 2
Z9 2
U1 2
U2 5
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1060-0280
EI 1542-6270
J9 ANN PHARMACOTHER
JI Ann. Pharmacother.
PD NOV
PY 2015
VL 49
IS 11
BP 1214
EP 1221
DI 10.1177/1060028015596998
PG 8
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA CU0OW
UT WOS:000363217800005
PM 26228936
ER
PT J
AU Laugsand, LE
Ix, JH
Bartz, TM
Djousse, L
Kizer, JR
Tracy, RP
Dehghan, A
Rexrode, K
Lopez, OL
Rimm, EB
Siscovick, DS
O'Donnell, CJ
Newman, A
Mukamal, KJ
Jensen, MK
AF Laugsand, Lars E.
Ix, Joachim H.
Bartz, Traci M.
Djousse, Luc
Kizer, Jorge R.
Tracy, Russell P.
Dehghan, Abbas
Rexrode, Kathryn
Lopez, Oscar L.
Rimm, Eric B.
Siscovick, David S.
O'Donnell, Christopher J.
Newman, Anne
Mukamal, Kenneth J.
Jensen, Majken K.
TI Fetuin-A and risk of coronary heart disease: A Mendelian randomization
analysis and a pooled analysis of AHSG genetic variants in 7 prospective
studies
SO ATHEROSCLEROSIS
LA English
DT Article
DE Fetuin-A; Single nucleotide polymorphisms; Coronary heart disease;
Mendelian randomization; Meta-analysis
ID ALPHA(2)-HEREMANS-SCHMID GLYCOPROTEIN/FETUIN-A; INCIDENT
DIABETES-MELLITUS; CARDIOVASCULAR HEALTH; OLDER-ADULTS;
INSULIN-RECEPTOR; TYROSINE KINASE; ASSOCIATION; ATHEROSCLEROSIS;
INHIBITOR; CALCIFICATION
AB Background and aims: Fetuin-A has a plausible role in the inhibition of arterial calcification, but its association with risk of coronary heart disease (CHD) in the general population is unclear. We used two common genetic variants in the fetuin-A gene (AHSG) that are strongly associated with circulating fetuin-A levels to investigate the associations with risk of CHD and subclinical cardiovascular measures (intima-media thickness, ankle-arm index, and coronary artery calcification).
Methods: Genetic variation and fetuin-A levels were assessed in 3299 community-living individuals (2733 Caucasians and 566 African Americans) 65 years of age or older, free of previous cardiovascular disease, who participated in the Cardiovascular Health Study (CHS) in 1992-1993.
Results: Among Caucasians, both rs2248690 and rs4917 were associated with 12% lower fetuin-A concentrations per minor allele (P < 0.0001). The hazard ratios (HRs) per minor allele for incident CHD were 1.12 (95% CI: 1.00-1.26) for rs2248690 and 1.02 (0.91-1.14) for rs4917. Using both genotypes as an instrumental variable for measured fetuin-A, the HRs for one standard deviation increase in genetically determined fetuin-A levels on CHD risk were 0.84 (95% CI: 0.70-1.00) for rs2248690 and 0.97 (95% CI: 0.82-1.14) for rs4917, respectively. However, in CHS neither of the genotypes were associated with subclinical cardiovascular measures and when CHS data were meta-analyzed with data from six other prospective studies (totaling 26,702 Caucasian participants and 3295 CHD cases), the meta-analyzed HRs for incident CHD were 1.12 (0.93-1.34) and 1.06 (0.93-1.20) for rs2248690 and rs4917, respectively (p heterogeneity 0.005 and 0.0048).
Conclusion: Common variants in the AHSG gene are strongly associated with fetuin-A levels, but their concurrent association with CHD risk in current prospective studies is inconsistent. Further investigation in studies with measured fetuin-A and AHSG variants is needed to clarify the potential causal association of fetuin-A with CHD risk. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
C1 [Laugsand, Lars E.] Norwegian Univ Sci & Technol, Fac Med, Dept Publ Hlth, N-7034 Trondheim, Norway.
[Laugsand, Lars E.; Rimm, Eric B.; Jensen, Majken K.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Ix, Joachim H.] Vet Affairs San Diego Healthcare Syst, Nephrol Sect, San Diego, CA USA.
[Ix, Joachim H.] Univ Calif San Diego, Div Nephrol, San Diego, CA 92103 USA.
[Ix, Joachim H.] Univ Calif San Diego, Div Prevent Med, San Diego, CA 92103 USA.
[Bartz, Traci M.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Djousse, Luc] Boston Vet Affairs Healthcare Syst, Boston, MA USA.
[Djousse, Luc; Rexrode, Kathryn] Brigham & Womens Hosp, Div Aging, Boston, MA 02115 USA.
[Kizer, Jorge R.] Albert Einstein Coll Med, Dept Med, New York, NY USA.
[Kizer, Jorge R.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, New York, NY USA.
[Tracy, Russell P.] Univ Vermont, Coll Med, Dept Pathol & Biochem, Burlington, VT 05405 USA.
[Dehghan, Abbas] Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands.
[Lopez, Oscar L.] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15260 USA.
[Kizer, Jorge R.; Rimm, Eric B.; Jensen, Majken K.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Div Network Med,Dept Med, Boston, MA 02115 USA.
[Siscovick, David S.] Univ Washington, Dept Med Epidemiol & Hlth Serv, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.
[Siscovick, David S.] Grp Hlth Res Inst, Grp Hlth Cooperat, Seattle, WA USA.
[O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, Framingham, MA USA.
[O'Donnell, Christopher J.] NHLBI, Div Intramural Res, Bethesda, MD 20892 USA.
[O'Donnell, Christopher J.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA.
[Newman, Anne] UPMC, Univ Pittsburgh, Sch Hlth Sci, Pittsburgh, PA USA.
[Mukamal, Kenneth J.] Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA.
RP Jensen, MK (reprint author), Harvard Univ, TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
RI Djousse, Luc/F-5033-2017; Newman, Anne B./C-6408-2013;
OI Djousse, Luc/0000-0002-9902-3047; Newman, Anne B./0000-0002-0106-1150;
Rexrode, Kathryn/0000-0003-3387-8429; Dehghan, Abbas/0000-0001-6403-016X
FU National Heart, Lung, and Blood Institute (NHLBI) [R01 HL094555]; NHLBI
CARe project (Broad Institute of Massachusetts Institute of Technology
and Harvard) [N01HC65226]; NHLBI [HL080295]; National Institute on Aging
(NIA) [R01AG023629]; Liaison Committee; National Institutes of Health,
Bethesda, MD [HL35464, CA55075, CA87969, HL34594]; NIH [N01-AG-12100];
NIA Intramural Research Program; Althingi (the Icelandic Parliament);
National Heart, Lung, and Blood Institute [HHSN268201100005C,
HHSN268201100006C, HHSN268201100007C, HHSN268201100008C,
HHSN268201100009C, HHSN268201100010C, HHSN268201100011C,
HHSN268201100012C, R01HL087641, R01HL59367, R01HL086694]; National Human
Genome Research Institute [U01HG004402]; National Institutes of Health
[HHSN268200625226C]; National Heart, Lung and Blood Institute's
Framingham Heart Study [N01-HC-25195]; Affymetrix, Inc [N02-HL-6-4278];
Netherlands Organization for Scientific Research (NWO) [916.12.154]; EUR
Fellowship; Erasmus University Rotterdam; Netherlands Organization for
Health Research and Development (ZonMw); Research Institute for Diseases
in the Elderly (RIDE); Netherlands Heart Foundation; Ministry of
Education, Culture and Science; Ministry of Health Welfare and Sports;
European Commission; Municipality of Rotterdam; Netherlands Genomics
Initiative (NGI)/Netherlands Consortium for Healthy Aging (NCHA)
[050-060-810]; National Institutes of Aging; NIA [N01AG62101,
N01AG62103, N01AG62106, 1R01AG032098-01A1]; Hjartavernd (the Icelandic
Heart Association); Erasmus Medical Center; [HHSN268201200036C];
[HHSN268200800007C]; [N01HC55222]; [N01HC85079]; [N01HC85080];
[N01HC85081]; [N01HC85082]; [N01HC85083]; [NO1HC85086]
FX The manuscript was supported by a grant from the National Heart, Lung,
and Blood Institute (NHLBI) (R01 HL094555 to LD, J.R.K.J.H.I, and K.J.M)
and genotyping was funded by the NHLBI CARe project (Broad Institute of
Massachusetts Institute of Technology and Harvard, N01HC65226). The
Cardiovascular Health Study was supported by contracts
HHSN268201200036C, HHSN268200800007C, N01HC55222, N01HC85079,
N01HC85080, N01HC85081, N01HC85082, N01HC85083, and NO1HC85086, and by
grant HL080295 from NHLBI, with additional contribution from the
National Institute of Neurological Disorders and Stroke (NINDS).
Additional support was provided by R01AG023629 from the National
Institute on Aging (NIA). A complete list of principal CHS investigators
and institutions can be found at http://www.chs-nhlbi.org/PI.htm. Lars
E. Laugsand received a research fellowship grant from the Liaison
Committee between the Central Norway Regional Health Authority and the
Norwegian University of Science and Technology.; Replication studies;
The HPFS CHD case-control study was supported by HL35464, and CA55075
from the National Institutes of Health, Bethesda, MD, with additional
support for genotyping from Merck/Rosetta Research Laboratories, North
Wales, PA. NHS: The NHS CHD case-control study was supported by CA87969
and HL34594 from the National Institutes of Health, Bethesda, MD, with
additional support for genotyping from Merck/Rosetta Research
Laboratories, North Wales, PA.; CHARGE cohorts: AGES study was funded by
NIH contract N01-AG-12100, the NIA Intramural Research Program,
Hjartavernd (the Icelandic Heart Association), and the Althingi (the
Icelandic Parliament). ARIC is supported by National Heart, Lung, and
Blood Institute contracts (HHSN268201100005C, HHSN268201100006C,
HHSN268201100007C, HHSN268201100008C, HHSN268201100009C,
HHSN268201100010C, HHSN268201100011C, and HHSN268201100012C),
R01HL087641, R01HL59367 and R01HL086694; National Human Genome Research
Institute contract U01HG004402; and National Institutes of Health
contract HHSN268200625226C. FHS was partially supported by the National
Heart, Lung and Blood Institute's Framingham Heart Study (N01-HC-25195)
and its contract with Affymetrix, Inc for genotyping services
(N02-HL-6-4278). Abbas Dehghan is supported by Netherlands Organization
for Scientific Research (NWO) grant (veni, 916.12.154) and the EUR
Fellowship. Rotterdam Study is supported by the Erasmus Medical Center
and Erasmus University Rotterdam; the Netherlands Organization for
Scientific Research (NWO); the Netherlands Organization for Health
Research and Development (ZonMw); the Research Institute for Diseases in
the Elderly (RIDE); the Netherlands Heart Foundation; the Ministry of
Education, Culture and Science; the Ministry of Health Welfare and
Sports; the European Commission; and the Municipality of Rotterdam.
Support for genotyping was provided by the Netherlands Organisation of
Scientific Research NWO Investments (nr. 175.010.2005.011, 911-03-012),
the Research Institute for Diseases in the Elderly (014-93-015; RIDE2),
the Netherlands Genomics Initiative (NGI)/Netherlands Consortium for
Healthy Aging (NCHA) project nr. 050-060-810. Health ABC was funded by
the National Institutes of Aging. This research was supported by NIA
contracts N01AG62101, N01AG62103, and N01AG62106. The genome-wide
association study was funded by NIA grant 1R01AG032098-01A1 to Wake
Forest University Health Sciences and genotyping services were provided
by the Center for Inherited Disease Research (CIDR).
NR 38
TC 2
Z9 2
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 NOV
PY 2015
VL 243
IS 1
BP 44
EP 52
DI 10.1016/j.atherosclerosis.2015.08.031
PG 9
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA CU1FQ
UT WOS:000363266000006
PM 26343871
ER
PT J
AU Lucero, D
Sviridov, D
Freeman, L
Lopez, GI
Fassio, E
Remaley, AT
Schreier, L
AF Lucero, Diego
Sviridov, Denis
Freeman, Lita
Lopez, Graciela I.
Fassio, Eduardo
Remaley, Alan T.
Schreier, Laura
TI Increased cholesterol efflux capacity in metabolic syndrome: Relation
with qualitative alterations in HDL and LCAT (vol 224, pg 236, 2015)
SO ATHEROSCLEROSIS
LA English
DT Correction
C1 [Lucero, Diego; Lopez, Graciela I.; Schreier, Laura] Univ Buenos Aires, Fac Pharm & Biochem, Dept Clin Biochem, Lab Lipids & Atherosclerosis,INFIBIOC, Buenos Aires, DF, Argentina.
[Lucero, Diego; Sviridov, Denis; Freeman, Lita; Remaley, Alan T.] NHLBI, Lipoprot Metab Sect, NIH, Bethesda, MD 20892 USA.
[Fassio, Eduardo] Natl Hosp Prof A Posadas, Dept Gastroenterol, Buenos Aires, DF, Argentina.
RP Lucero, D (reprint author), Univ Buenos Aires, Fac Pharm & Biochem, Dept Clin Biochem, Junin 956 C1113AAD, Buenos Aires, DF, Argentina.
EM dmlucero@ffyb.uba.ar
NR 1
TC 0
Z9 0
U1 0
U2 2
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 NOV
PY 2015
VL 243
IS 1
BP 59
EP 59
DI 10.1016/j.atherosclerosis.2015.08.041
PG 1
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA CU1FQ
UT WOS:000363266000008
ER
PT J
AU Im, A
Pavletic, SZ
AF Im, Annie
Pavletic, Steven Z.
TI Deciphering the Mystery: Extracorporeal Photopheresis in
Graft-versus-Host Disease
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Editorial Material
ID PEDIATRIC-PATIENTS; PHOTOCHEMOTHERAPY; TRANSPLANTATION
C1 [Im, Annie] Univ Pittsburgh, Med Ctr, Div Hematol Oncol, Pittsburgh, PA USA.
[Pavletic, Steven Z.] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Pavletic, SZ (reprint author), NCI, Graft Versus Host Dis & Autoimmun Unit, Expt Transplantat & Immunol Branch, Ctr Canc Res,NIH, 10 Ctr Dr,Bldg 10,Room CRC 4-3130, Bethesda, MD 20892 USA.
EM pavletis@mail.nih.gov
OI Im, Annie/0000-0002-0973-7100
NR 12
TC 0
Z9 0
U1 1
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1083-8791
EI 1523-6536
J9 BIOL BLOOD MARROW TR
JI Biol. Blood Marrow Transplant.
PD NOV
PY 2015
VL 21
IS 11
BP 1861
EP 1862
DI 10.1016/j.bbmt.2015.09.011
PG 2
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA CU2MI
UT WOS:000363357200002
PM 26386319
ER
PT J
AU Torres, HA
Chong, PP
De Lima, M
Friedman, MS
Giralt, S
Hammond, SP
Kiel, PJ
Masur, H
McDonald, GB
Wingard, JR
Gambarin-Gelwan, M
AF Torres, Harrys A.
Chong, Pearlie P.
De Lima, Marcos
Friedman, Mark S.
Giralt, Sergio
Hammond, Sarah P.
Kiel, Patrick J.
Masur, Henry
McDonald, George B.
Wingard, John R.
Gambarin-Gelwan, Maya
TI Hepatitis C Virus Infection among Hematopoietic Cell Transplant Donors
and Recipients: American Society for Blood and Marrow Transplantation
Task Force Recommendations
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Article
ID GENOTYPE 1 INFECTION; TREATMENT-NAIVE PATIENTS; LIVER-TRANSPLANTATION;
TRANSIENT ELASTOGRAPHY; PEGYLATED INTERFERON; ACUTE EXACERBATION;
LIVING-DONOR; FOLLOW-UP; B-VIRUS; HCV
C1 [Torres, Harrys A.] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Chong, Pearlie P.] Univ N Carolina, Chapel Hill, NC USA.
[De Lima, Marcos] Case Western Reserve Univ, Univ Hosp Case Med Ctr, Cleveland, OH 44106 USA.
[De Lima, Marcos] Case Western Reserve Univ, Univ Hosp Seidman Canc Ctr, Cleveland, OH 44106 USA.
[Friedman, Mark S.] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA.
[Giralt, Sergio; Gambarin-Gelwan, Maya] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
[Hammond, Sarah P.] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Hammond, Sarah P.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Kiel, Patrick J.] Indiana Univ, Simon Canc Ctr, Indianapolis, IN 46204 USA.
[Masur, Henry] NIH, Ctr Clin, Bethesda, MD 20892 USA.
[McDonald, George B.] Univ Washington, Seattle, WA 98195 USA.
[McDonald, George B.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Wingard, John R.] Univ Florida, Gainesville, FL USA.
RP Torres, HA (reprint author), Univ Texas MD Anderson Canc Ctr, Unit 1460, 1515 Holcombe Blvd, Houston, TX 77030 USA.
EM htorres@mdanderson.org
FU University of Texas MD Anderson Cancer Center; Gilead Sciences; Merck
Co., Inc.; Vertex Pharmaceuticals; Ansun Biopharma; Hoffman-La Roche;
Coley Pharmaceutical; GlaxoSmithKline; LabCorp Corporation; Conatus
Pharmaceuticals; Bristol-Myers Squibb
FX H.A.T. is a consultant for Janssen Pharmaceuticals, Inc., Gilead
Sciences, Merck & Co., Inc., Vertex Pharmaceuticals, Novartis,
Genentech, Astellas, Pfizer, and Theravance, Inc. and has received
research grants from The University of Texas MD Anderson Cancer Center,
Gilead Sciences, Merck & Co., Inc., and Vertex Pharmaceuticals. S.P.H.
has received research grants from Merck & Co., Inc. and Ansun Biopharma.
J.R.W. is a consultant for Ansun, Gilead Sciences, Merck & Co, and
Astellas; speaker for Pfizer; and has received royalties from UpToDate
Inc. M.G.G. is a consultant for Gilead Sciences, Bristol-Myers Squibb
and has received research grants from Hoffman-La Roche, Coley
Pharmaceutical, GlaxoSmithKline, LabCorp Corporation, Conatus
Pharmaceuticals, Bristol-Myers Squibb, and Gilead Sciences. The
remaining authors have no conflicts of interest to declare.
NR 69
TC 9
Z9 10
U1 2
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1083-8791
EI 1523-6536
J9 BIOL BLOOD MARROW TR
JI Biol. Blood Marrow Transplant.
PD NOV
PY 2015
VL 21
IS 11
BP 1870
EP 1882
DI 10.1016/j.bbmt.2015.07.033
PG 13
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA CU2MI
UT WOS:000363357200004
PM 26256943
ER
PT J
AU Kiselev, E
Balasubramanian, R
Uliassi, E
Brown, KA
Trujillo, K
Katritch, V
Hammes, E
Stevens, RC
Harden, TK
Jacobson, KA
AF Kiselev, Evgeny
Balasubramanian, Ramachandran
Uliassi, Elisa
Brown, Kyle A.
Trujillo, Kevin
Katritch, Vsevolod
Hammes, Eva
Stevens, Raymond C.
Harden, T. Kendall
Jacobson, Kenneth A.
TI Design, synthesis, pharmacological characterization of a fluorescent
agonist of the P2Y(14) receptor
SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
LA English
DT Article
DE G protein-coupled receptor; Nucleotides; Pyrimidines; Homology modeling;
Docking; P2Y receptor
ID HUMAN NEUTROPHILS; MOLECULAR PROBES; DERIVATIVES; ANTAGONISTS;
CHEMOTAXIS; TEMPLATE; POTENT; MICE
AB The P2Y(14)R is a G(i/o)-coupled receptor of the P2Y family of purinergic receptors that is activated by extracellular UDP and UDP-glucose (UDPG). In an earlier report we described a P2Y(14)R fluorescent probe, MRS4174, based on the potent and selective antagonist PPTN, a naphthoic acid derivative. Here, we report the design, preparation, and activity of an agonist-based fluorescent probe MRS4183 (11) and a shorter P2Y(14)R agonist congener, which contain a UDP-glucuronic acid pharmacophore and BODIPY fluorophores conjugated through diaminoalkyl linkers. The design relied on both docking in a P2Y(14)R homology model and established structure activity relationship (SAR) of nucleotide analogs. 11 retained P2Y(14)R potency with EC50 value of 0.96 nM (inhibition of adenylyl cyclase), compared to parent UDPG (EC50 47 nM) and served as a tracer for microscopy and flow cytometry, displaying minimal nonspecific binding. Binding saturation analysis gave an apparent binding constant for 11 in whole cells of 21.4 +/- 1.1 nM, with a t(1/2) of association at 50 nM 11 of 23.9 min. Known P2Y(14)R agonists and PPTN inhibited cell binding of 11 with the expected rank order of potency. The success in the identification of a new P2Y(14)R fluorescent agonist with low nonspecific binding illustrates the advantages of rational design based on recently determined GPCR X-ray structures. Such conjugates will be useful tools in expanding the SAR of this receptor, which still lacks chemical diversity in its collective ligands. Published by Elsevier Ltd.
C1 [Kiselev, Evgeny; Balasubramanian, Ramachandran; Uliassi, Elisa; Trujillo, Kevin; Hammes, Eva; Jacobson, Kenneth A.] NIDDK, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
[Brown, Kyle A.; Harden, T. Kendall] Univ N Carolina, Sch Med, Dept Pharmacol, Chapel Hill, NC 27599 USA.
[Katritch, Vsevolod; Stevens, Raymond C.] Univ So Calif, Bridge Inst, Dept Biol Sci, Dornsife Coll Letters Arts & Sci, Los Angeles, CA 90089 USA.
[Stevens, Raymond C.] Univ So Calif, Bridge Inst, Dept Chem, Dornsife Coll Letters Arts & Sci, Los Angeles, CA 90089 USA.
RP Jacobson, KA (reprint author), NIDDK, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
EM kajacobs@helix.nih.gov
RI Jacobson, Kenneth/A-1530-2009; Katritch, Vsevolod/Q-8357-2016
OI Jacobson, Kenneth/0000-0001-8104-1493;
FU National Institutes of Health (Intramural Research Program of the NIDDK)
[Z01 DK031116]; NIGMS Postdoctoral Research Associate (PRAT) Program
[GM38213, U54GM094618]
FX We thank Dr. John Lloyd and Dr. Noel Whittaker (NIDDK) for mass spectral
determinations. This research was supported by the National Institutes
of Health (Intramural Research Program of the NIDDK, Z01 DK031116),
NIGMS Postdoctoral Research Associate (PRAT) Program and Grant nos.
GM38213 to T.K.H. and U54GM094618 to V.K. and R.C.S.
NR 25
TC 4
Z9 4
U1 2
U2 14
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0960-894X
EI 1464-3405
J9 BIOORG MED CHEM LETT
JI Bioorg. Med. Chem. Lett.
PD NOV 1
PY 2015
VL 25
IS 21
BP 4733
EP 4739
DI 10.1016/j.bmcl.2015.08.021
PG 7
WC Chemistry, Medicinal; Chemistry, Organic
SC Pharmacology & Pharmacy; Chemistry
GA CU1IV
UT WOS:000363275400007
PM 26303895
ER
PT J
AU Gupta, P
Rastede, EE
Appella, DH
AF Gupta, Pankaj
Rastede, Elizabeth E.
Appella, Daniel H.
TI Multivalent K-L gamma-PNA oligomers bind to a human telomere DNA G-rich
sequence to form quadruplexes
SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
LA English
DT Article
DE Quadruplex; DNA; PNA
ID PEPTIDE NUCLEIC-ACIDS; COMPLEMENTARY; RNA; HYBRIDIZATION;
OLIGONUCLEOTIDES; RECOGNITION; TRANSLATION; SELECTIVITY; STABILITY;
PROMOTER
AB We report G-quadruplex formation between peptide nucleic acids (PNAs) composed of K-L gamma-PNA-G monomers and a known portion of human telomeric DNA that adopts three G3 tracts via intramolecular hydrogen bonding. The resulting complex is a bimolecular PNA-DNA heteroquadruplex. In this Letter, we show that introduction of a gamma-modification and addition of a peptide ligand does not disrupt the heteroquadruplex. Although the unmodified PNA1 forms a quadruplex with itself, the gamma-substituted PNAs (PNA2-PNA6) do not form G-quadruplexes on their own, at even high concentrations. The selectivity of these PNAs could influence the design of new quadruplex-targeting molecules or allow the quadruplex structure to be used as a scaffold for multivalent display of protein binding ligands. Published by Elsevier Ltd.
C1 [Gupta, Pankaj; Rastede, Elizabeth E.; Appella, Daniel H.] NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
RP Appella, DH (reprint author), NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
EM appellad@niddk.nih.gov
FU Intramural Research Program of NIDDK, NIH
FX This research was supported by the Intramural Research Program of NIDDK,
NIH.
NR 48
TC 0
Z9 0
U1 3
U2 17
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0960-894X
EI 1464-3405
J9 BIOORG MED CHEM LETT
JI Bioorg. Med. Chem. Lett.
PD NOV 1
PY 2015
VL 25
IS 21
BP 4757
EP 4760
DI 10.1016/j.bmcl.2015.07.075
PG 4
WC Chemistry, Medicinal; Chemistry, Organic
SC Pharmacology & Pharmacy; Chemistry
GA CU1IV
UT WOS:000363275400010
PM 26259805
ER
PT J
AU Stratton, CF
Newman, DJ
Tan, DS
AF Stratton, Christopher F.
Newman, David J.
Tan, Derek S.
TI Cheminformatic comparison of approved drugs from natural product versus
synthetic origins
SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
LA English
DT Article
DE Natural products; Synthetic drugs; Physicochemical properties;
Cheminformatics; Principal component analysis
ID DIVERSITY-ORIENTED SYNTHESIS; SMALL MOLECULES; CHEMICAL SPACE; ORAL
BIOAVAILABILITY; RING EXPANSION; DISCOVERY; LIBRARY; TARGETS;
DISTRIBUTIONS; PERMEABILITY
AB Despite the recent decline of natural product discovery programs in the pharmaceutical industry, approximately half of all new drug approvals still trace their structural origins to a natural product. Herein, we use principal component analysis to compare the structural and physicochemical features of drugs from natural product-based versus completely synthetic origins that were approved between 1981 and 2010. Drugs based on natural product structures display greater chemical diversity and occupy larger regions of chemical space than drugs from completely synthetic origins. Notably, synthetic drugs based on natural product pharmacophores also exhibit lower hydrophobicity and greater stereochemical content than drugs from completely synthetic origins. These results illustrate that structural features found in natural products can be successfully incorporated into synthetic drugs, thereby increasing the chemical diversity available for small-molecule drug discovery. (C) 2015 Elsevier Ltd. All rights reserved.
C1 [Stratton, Christopher F.; Tan, Derek S.] Mem Sloan Kettering Canc Ctr, Triinst PhD Program Chem Biol, New York, NY 10065 USA.
[Newman, David J.] NCI, Nat Prod Branch, Dev Therapeut Program, Div Canc Treatment & Diag, Ft Detrick, MD 21702 USA.
[Tan, Derek S.] Mem Sloan Kettering Canc Ctr, Chem Biol Program, New York, NY 10065 USA.
[Tan, Derek S.] Mem Sloan Kettering Canc Ctr, Triinst Res Program, New York, NY 10065 USA.
RP Tan, DS (reprint author), Mem Sloan Kettering Canc Ctr, Triinst PhD Program Chem Biol, 1275 York Ave,Box 422, New York, NY 10065 USA.
FU NIH [P41 GM076267]; Tri-Institutional Stem Cell Initiative; Commonwealth
Foundation for Cancer Research; MSKCC Experimental Therapeutics Center
FX This work is dedicated to the memory of our mentor and colleague,
Professor David Y. Gin (1967-2011). Instant JChem was generously
provided by ChemAxon. Financial support from the NIH (P41 GM076267 to
D.S.T.), Tri-Institutional Stem Cell Initiative, William H. Goodwin and
Alice Goodwin and the Commonwealth Foundation for Cancer Research, and
the MSKCC Experimental Therapeutics Center is gratefully acknowledged.
NR 48
TC 8
Z9 9
U1 7
U2 19
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0960-894X
EI 1464-3405
J9 BIOORG MED CHEM LETT
JI Bioorg. Med. Chem. Lett.
PD NOV 1
PY 2015
VL 25
IS 21
BP 4802
EP 4807
DI 10.1016/j.bmcl.2015.07.014
PG 6
WC Chemistry, Medicinal; Chemistry, Organic
SC Pharmacology & Pharmacy; Chemistry
GA CU1IV
UT WOS:000363275400020
PM 26254944
ER
PT J
AU Ghosh, AK
Takayama, J
Kassekert, LA
Ella-Menye, JR
Yashchuk, S
Agniswamy, J
Wang, YF
Aoki, M
Amano, M
Weber, IT
Mitsuya, H
AF Ghosh, Arun K.
Takayama, Jun
Kassekert, Luke A.
Ella-Menye, Jean-Rene
Yashchuk, Sofiya
Agniswamy, Johnson
Wang, Yuan-Fang
Aoki, Manabu
Amano, Masayuki
Weber, Irene T.
Mitsuya, Hiroaki
TI Structure-based design, synthesis, X-ray studies, and biological
evaluation of novel HIV-1 protease inhibitors containing
isophthalamide-derived P2-ligands
SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
LA English
DT Article
DE HIV-1 protease; Inhibitors; Design; Synthesis; Antiviral; Isophthalamide
ID ACTIVE ANTIRETROVIRAL THERAPY; RESOLUTION CRYSTAL-STRUCTURES;
BETA-SECRETASE INHIBITORS; COMBAT DRUG-RESISTANCE; LIGAND; INFECTION;
COMPLEXES; MUTANTS
AB We describe the design, synthesis and biological evaluation of a series of novel HIV-1 protease inhibitors bearing isophthalamide derivatives as the P2-P3 ligands. We have investigated a range of acyclic and heterocyclic amides as the extended P2-P3 ligands. These inhibitors displayed good to excellent HIV-1 protease inhibitory activity. Also, a number of inhibitors showed very good antiviral activity in MT cells. Compound 5n has shown an enzyme K-i of 0.17 nM and antiviral IC50 of 14 nM. An X-ray crystal structure of inhibitor 5o-bound to HIV-1 protease was determined at 1.11 angstrom resolution. This structure revealed important molecular insight into the inhibitor-HIV-1 protease interactions in the active site. (C) 2015 Elsevier Ltd. All rights reserved.
C1 [Ghosh, Arun K.; Takayama, Jun; Kassekert, Luke A.; Ella-Menye, Jean-Rene; Yashchuk, Sofiya] Purdue Univ, Dept Chem, W Lafayette, IN 47907 USA.
[Ghosh, Arun K.; Takayama, Jun; Kassekert, Luke A.; Ella-Menye, Jean-Rene; Yashchuk, Sofiya] Purdue Univ, Dept Med Chem, W Lafayette, IN 47907 USA.
[Agniswamy, Johnson; Wang, Yuan-Fang; Weber, Irene T.] Georgia State Univ, Dept Biol, Atlanta, GA 30303 USA.
[Agniswamy, Johnson; Wang, Yuan-Fang; Weber, Irene T.] Georgia State Univ, Dept Chem, Atlanta, GA 30303 USA.
[Aoki, Manabu; Amano, Masayuki; Mitsuya, Hiroaki] Kumamoto Univ Med, Dept Hematol, Kumamoto 8608556, Japan.
[Aoki, Manabu; Amano, Masayuki; Mitsuya, Hiroaki] Kumamoto Univ Med, Dept Infect Dis, Kumamoto 8608556, Japan.
[Mitsuya, Hiroaki] NCI, Expt Retrovirol Sect, HIV & AIDS Malignancy Branch, Bethesda, MD 20892 USA.
[Mitsuya, Hiroaki] Natl Ctr Global Hlth & Med, Ctr Clin Sci, Shinjuku Ku, Tokyo 1628655, Japan.
RP Ghosh, AK (reprint author), Purdue Univ, Dept Chem, W Lafayette, IN 47907 USA.
EM akghosh@purdue.edu
RI Amano, Masayuki/N-7407-2016
OI Amano, Masayuki/0000-0003-0516-9502
FU National Institutes of Health [GM53386, GM62920]; U.S. Department of
Energy, Basic Energy Sciences, Office of Science [W-31-109-Eng-38];
Intramural Research Program of the Center for Cancer Research, National
Cancer Institute, National Institutes of Health; Ministry of Education,
Culture, Sports, Science, and Technology of Japan (Monbu Kagakusho);
Ministry of Health, Welfare, and Labor of Japan; Cooperative Research
Project on Clinical and Epidemiological Studies of Emerging and
Reemerging Infectious Diseases (Renkei Jigyo) of Monbu-Kagakusho
FX This research was supported by the National Institutes of Health (Grant
GM53386, A.K.G. and Grant GM62920, I.T.W.). X-ray data were collected at
the Southeast Regional Collaborative Access Team (SER-CAT) beamline 22BM
at the Advanced Photon Source, Argonne National Laboratory. Use of the
Advanced Photon Source was supported by the U.S. Department of Energy,
Basic Energy Sciences, Office of Science, under Contract No.
W-31-109-Eng-38. This work was also supported by the Intramural Research
Program of the Center for Cancer Research, National Cancer Institute,
National Institutes of Health, and in part by a Grant-in-Aid for
Scientific Research (Priority Areas) from the Ministry of Education,
Culture, Sports, Science, and Technology of Japan (Monbu Kagakusho), a
Grant for Promotion of AIDS Research from the Ministry of Health,
Welfare, and Labor of Japan, and the Grant to the Cooperative Research
Project on Clinical and Epidemiological Studies of Emerging and
Reemerging Infectious Diseases (Renkei Jigyo) of Monbu-Kagakusho. The
authors would like to thank the Purdue University Center for Cancer
Research, which supports the shared NMR and mass spectrometry
facilities.
NR 34
TC 3
Z9 3
U1 2
U2 20
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0960-894X
EI 1464-3405
J9 BIOORG MED CHEM LETT
JI Bioorg. Med. Chem. Lett.
PD NOV 1
PY 2015
VL 25
IS 21
BP 4903
EP 4909
DI 10.1016/j.bmcl.2015.05.052
PG 7
WC Chemistry, Medicinal; Chemistry, Organic
SC Pharmacology & Pharmacy; Chemistry
GA CU1IV
UT WOS:000363275400041
PM 26096678
ER
PT J
AU Jensen, JD
Ratcliff, C
Weaver, J
Krakow, MM
Payton, W
Loewen, S
AF Jensen, Jakob D.
Ratcliff, Chelsea
Weaver, Jeremy
Krakow, Melinda M.
Payton, William
Loewen, Sherrie
TI Explicating perceived barriers to mammography for the USCREEN project:
concerns about breast implants, faith violations, and perceived
recommendations
SO BREAST CANCER RESEARCH AND TREATMENT
LA English
DT Article
DE Perceived barriers; Health belief model; Mammography; Breast implants;
Faith; News coverage
ID SERVICES TASK-FORCE; HEALTH BELIEF MODEL; AFRICAN-AMERICAN WOMEN; CHURCH
ATTENDANCE; SELF-EFFICACY; CANCER; PREDICTORS; VARIABLES; BENEFITS;
SCALE
AB In line with the health belief model, perceived barriers have proven to be a key determinant of intentions to screen for breast cancer. The standard measure of perceived barriers to breast cancer screening is an 11 item scale developed by Victoria Champion. However, perceived barriers emerge and change over time, and Champion's perceived barriers scale was last revised in 1999. Moreover, the original scale did not address barriers which may be more pronounced in particular populations, such as congruity of action with faith. As part of the Utah Screening Project, a sample of women 40-74 (N = 341, Mage = 51.19, SD = 8.11) were recruited from four Utah counties in 2014 to complete a survey. The results revealed that the four new perceived barrier items explained 6.4 % of intentions to screen, above and beyond other predictors. In addition to barriers identified in past research, the current study identified several novel barriers including (a) concerns about negative effects to breast implants, (b) perceived conflict with faith, and the (c) perception that mammography is no longer recommended. The new perceived barriers items are useful to researchers interested in exploring barriers not addressed by the original instrument. The barriers also suggest potential belief-based targets and channels (e.g., plastic surgery clinics, faith-based interventions) for delivering mammography interventions.
C1 [Jensen, Jakob D.; Ratcliff, Chelsea; Weaver, Jeremy; Payton, William; Loewen, Sherrie] Univ Utah, Dept Commun, Salt Lake City, UT 84112 USA.
[Jensen, Jakob D.] Huntsman Canc Inst, Salt Lake City, UT USA.
[Krakow, Melinda M.] NCI, Canc Prevent Div, Bethesda, MD 20892 USA.
RP Jensen, JD (reprint author), Univ Utah, Dept Commun, 2423 LNCO,255 S Cent Campus Dr, Salt Lake City, UT 84112 USA.
EM jakobdjensen@gmail.com
FU Utah Department of Health
FX Jakob D. Jensen is an Associate Professor in the Department of
Communication and the Huntsman Cancer Institute at the University of
Utah. Chelsea Ratcliff, Jeremy Weaver, William Payton, and Sherrie
Loewen are graduate students in the Department of Communication at the
University of Utah. Melinda Krakow is a post-doctoral fellow at the
National Cancer Institute. This research was funded by a grant from the
Utah Department of Health.
NR 30
TC 0
Z9 0
U1 2
U2 6
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0167-6806
EI 1573-7217
J9 BREAST CANCER RES TR
JI Breast Cancer Res. Treat.
PD NOV
PY 2015
VL 154
IS 1
BP 201
EP 207
DI 10.1007/s10549-015-3581-2
PG 7
WC Oncology
SC Oncology
GA CU4YP
UT WOS:000363538100023
PM 26424166
ER
PT J
AU Morgan, RJ
Synold, TW
Longmate, JA
Quinn, DI
Gandara, D
Lenz, HJ
Ruel, C
Xi, BX
Lewis, MD
Colevas, AD
Doroshow, J
Newman, EM
AF Morgan, Robert J.
Synold, Timothy W.
Longmate, Jeffrey A.
Quinn, David I.
Gandara, David
Lenz, Heinz-Josef
Ruel, Christopher
Xi, Bixin
Lewis, Michael D.
Colevas, A. Dimitrios
Doroshow, James
Newman, Edward M.
TI Pharmacodynamics (PD) and pharmacokinetics (PK) of E7389 (eribulin,
halichondrin B analog) during a phase I trial in patients with advanced
solid tumors: a California Cancer Consortium trial
SO CANCER CHEMOTHERAPY AND PHARMACOLOGY
LA English
DT Article
DE Pharmacodynamics; Pharmacokinetics; Eribulin; Halichondrin B analog;
Phase I trial
ID CELL LUNG-CANCER; MARINE NATURAL-PRODUCTS; MESYLATE E7389;
BREAST-CANCER; PACLITAXEL RESISTANCE; HOMOHALICHONDRIN-B; TUBULIN
MUTATIONS; VINCA DOMAIN; DRUGS; SENSITIVITY
AB The California Cancer Consortium completed a phase I trial of E7389 (eribulin mesylate), an analog of the marine natural product halichondrin B. This trial was to determine the pharmacodynamics, pharmacokinetics, and MTD of E7389 administered by bolus injection weekly for 3 weeks out of four.
This trial included a rapid titration design. Real-time pharmacokinetics were utilized to guide dose escalation. Initially, single-patient cohorts were enrolled with intra- and inter-patient dose doubling. The second phase was a standard 3 + 3 dose escalation schedule. At the MTD, a cohort of patients was enrolled for target validation studies (separate manuscript). The starting dose was 0.125 mg/m(2), and doses were doubled within and between patients in the first phase. Blood and urine sampling for E7389 pharmacokinetics was performed on doses 1 and 3 of cycle 1. Levels were determined using a LC/MS/MS assay.
Forty patients were entered. Thirty-eight were evaluable for toxicity and 35 for response. The rapid escalation ended with a grade 3 elevation of alkaline phosphatase at 0.5 mg/m(2)/week. The second phase ended at 2.0 mg/m(2)/week with dose-limiting toxicities of grades 3 and 4 febrile neutropenia. Other toxicities included hypoglycemia, hypophosphatemia, and fatigue. The MTD was 1.4 mg/m(2)/week. Responses included four partial responses (lung cancer [2], urothelial [1], and melanoma [1]).
E7389 was well tolerated in this trial with the major toxicity being myelosuppression. PD shows that E7389 induces significant morphologic changes (bundle formation) in the microtubules of peripheral blood mononuclear cells and tumor cells in vivo. The data suggest that lower intra-tumoral levels of beta-tubulin III or higher intra-tumoral levels of MAP4 may correlate with response to E7389, while lower intra-tumoral levels of stathmin may be associated with progression. PK data reveal that E7389 exhibits a tri-exponential elimination from the plasma of patients receiving a rapid i.v. infusion. At sub-toxic doses, plasma concentrations of E7389 are maintained well above the levels required for activity in vitro for > 72 h.
C1 [Morgan, Robert J.; Doroshow, James] City Hope Comprehens Canc Ctr, Dept Med Oncol & Therapeut Res, Duarte, CA 91010 USA.
[Synold, Timothy W.; Xi, Bixin; Newman, Edward M.] City Hope Comprehens Canc Ctr, Dept Canc Biol, Duarte, CA 91010 USA.
[Longmate, Jeffrey A.; Ruel, Christopher] City Hope Comprehens Canc Ctr, Dept Biostat, Duarte, CA 91010 USA.
[Quinn, David I.; Lenz, Heinz-Josef] Univ So Calif, Div Med Oncol, Kenneth Norris Jr Comprehens Canc Ctr, Los Angeles, CA 90033 USA.
[Gandara, David] Univ Calif Davis, Ctr Canc, Div Med Oncol, Sacramento, CA 95817 USA.
[Lewis, Michael D.] Eisai Res Inst, Andover, MA 01810 USA.
[Colevas, A. Dimitrios] NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA.
RP Morgan, RJ (reprint author), City Hope Comprehens Canc Ctr, Dept Med Oncol & Therapeut Res, 1500 E Duarte Rd, Duarte, CA 91010 USA.
EM rmorgan@coh.org
FU National Cancer Institute [P30CA033572, UM1CA186717, U01CA062505,
M01RR000043]
FX This study was supported in part by National Cancer Institute Grants
P30CA033572, UM1CA186717, U01CA062505, and M01RR000043.
NR 37
TC 3
Z9 3
U1 2
U2 10
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0344-5704
EI 1432-0843
J9 CANCER CHEMOTH PHARM
JI Cancer Chemother. Pharmacol.
PD NOV
PY 2015
VL 76
IS 5
BP 897
EP 907
DI 10.1007/s00280-015-2868-7
PG 11
WC Oncology; Pharmacology & Pharmacy
SC Oncology; Pharmacology & Pharmacy
GA CU0YR
UT WOS:000363245800002
PM 26362045
ER
PT J
AU Gulley, JL
Marte, J
Heery, CR
Madan, RA
Steinberg, SM
Leitman, SF
Tsang, KY
Schlom, J
AF Gulley, James L.
Marte, Jennifer
Heery, Christopher R.
Madan, Ravi A.
Steinberg, Seth M.
Leitman, Susan F.
Tsang, Kwong Y.
Schlom, Jeffrey
TI The impact of leukapheresis on immune-cell number and function in
patients with advanced cancer
SO CANCER IMMUNOLOGY IMMUNOTHERAPY
LA English
DT Article
DE Apheresis; Vaccine; Immunotherapy; Clinical trial
ID RESISTANT PROSTATE-CANCER; RE INTERDISCIPLINARY CRITIQUE;
COLONY-STIMULATING FACTOR; SIPULEUCEL-T; PHASE-I; METASTATIC CARCINOMA;
VACCINE; IMMUNOTHERAPY; ANTIGEN; CEA
AB Leukapheresis is often performed in cancer patients to harvest stem cells, manufacture therapeutic vaccines, or follow immunologic response to therapy. We have recently described the minimal impact of leukapheresis on normal donors. Here we provide additional immunologic data from patients with advanced cancer who underwent leukapheresis.
Using data from cancer patients on clinical trials who had leukapheresis (n = 64) or peripheral blood draws only (n = 90) as controls for immune analysis, we evaluated the impact of leukapheresis on number and function of lymphocytes.
In the leukapheresis group, median age was 63.5 (range 38-82); 87.5 % were male. Comparing pre- and post-leukapheresis values within the groups, with each patient as its own control, there was no significant difference in enzyme-linked immunosorbent spot (ELISPOT), antivector humoral response, absolute lymphocyte count (ALC), or T cell number. Twelve patients completed three leukaphereses with subsequent ELISPOT analysis; seven had increased responses to flu (1.1- to 2.3-fold) with an even distribution around no change. Nineteen patients had matched ALC values after completing three leukaphereses with no significant change from baseline.
These data provide evidence that leukapheresis has no detectable effects on a cancer patient's immune system in terms of number or function. These results contribute to a growing body of evidence refuting the hypothesis that a patient's immune competence is meaningfully affected by the procedure. Limitations include a restriction to 2-L leukapheresis procedure and small sample size.
C1 [Gulley, James L.; Marte, Jennifer; Madan, Ravi A.] NCI, Genitourinary Malignancies Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Gulley, James L.; Heery, Christopher R.; Tsang, Kwong Y.; Schlom, Jeffrey] NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Steinberg, Seth M.] NCI, Biostat & Data Management Sect, Off Clin Director, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
[Leitman, Susan F.] NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA.
RP Gulley, JL (reprint author), NCI, Genitourinary Malignancies Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM gulleyj@mail.nih.gov
RI Gulley, James/K-4139-2016
OI Gulley, James/0000-0002-6569-2912
FU National Institutes of Health (NIH), National Cancer Institute (NCI),
Center for Cancer Research; Center for Cancer Research, National Cancer
Institute, National Institutes of Health
FX The authors acknowledge the Intramural Research Program of the National
Institutes of Health (NIH), National Cancer Institute (NCI), Center for
Cancer Research for their support of this study. We also express
appreciation to the professionals at the NIH Clinical Center Department
of Transfusion Medicine for their part in performing apheresis
procedures in study patients and to the medical oncology fellows at the
NCI for their attention to patient care. Finally, we thank Bonnie L.
Casey and Debra Weingarten for their editorial assistance in the
preparation of this manuscript. This research was supported by the
Intramural Research Program of the Center for Cancer Research, National
Cancer Institute, National Institutes of Health.
NR 24
TC 1
Z9 1
U1 1
U2 5
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0340-7004
EI 1432-0851
J9 CANCER IMMUNOL IMMUN
JI Cancer Immunol. Immunother.
PD NOV
PY 2015
VL 64
IS 11
BP 1429
EP 1435
DI 10.1007/s00262-015-1738-9
PG 7
WC Oncology; Immunology
SC Oncology; Immunology
GA CU0ZE
UT WOS:000363247400007
PM 26243387
ER
PT J
AU Jones, GC
Kehrer, JD
Kahn, J
Koneru, BN
Narayan, R
Thomas, TO
Camphausen, K
Mehta, MP
Kaushal, A
AF Jones, Guy C.
Kehrer, Jason D.
Kahn, Jenna
Koneru, Bobby N.
Narayan, Ram
Thomas, Tarita O.
Camphausen, Kevin
Mehta, Minesh P.
Kaushal, Aradhana
TI Primary Treatment Options for High-Risk/Medically Inoperable Early Stage
NSCLC Patients
SO CLINICAL LUNG CANCER
LA English
DT Review
DE Intraoperative brachytherapy; Microwave ablation; Percutaneous
cryotherapy; Photodynamic therapy; Radiofrequency ablation; SBRT;
Stereotactic body radiotherapy
ID CELL LUNG-CANCER; BODY RADIATION-THERAPY; HIGH-RISK PATIENTS;
PERCUTANEOUS RADIOFREQUENCY ABLATION; PROSPECTIVE PHASE-II;
CLINICAL-PRACTICE GUIDELINES; PHOTODYNAMIC THERAPY; SUBLOBAR RESECTION;
LIMITED RESECTION; WEDGE RESECTION
AB Lung cancer is among the most common cancers worldwide and is the leading cause of cancer death in both men and women. For patients with early stage (American Joint Committee on Cancer T1-2, N0) non-small-cell lung cancer, the current standard of care is lobectomy with systematic lymph node evaluation. Unfortunately, patients with lung cancer often have medical comorbities, which may preclude the option of surgical resection. In such cases, a number of minimally invasive to noninvasive treatment options have gained popularity in the treatment of these high-risk patients. These modalities provide significant advantages, including patient convenience, treatment in an outpatient setting, and acceptable toxicities, including reduced impact on lung function and a modest risk of postprocedure chest wall pain. We provide a comprehensive review of the literature, including reported outcomes, complications, and limitations of sublobar resection with or without intraoperative brachytherapy, radiofrequency ablation, microwave ablation, percutaneous cryoablation, photodynamic therapy, and stereotactic body radiotherapy.
C1 [Jones, Guy C.; Kehrer, Jason D.; Kahn, Jenna; Koneru, Bobby N.; Narayan, Ram; Thomas, Tarita O.; Camphausen, Kevin; Mehta, Minesh P.; Kaushal, Aradhana] NCI, Bethesda, MD 20892 USA.
RP Jones, GC (reprint author), NCI, Radiat Oncol Branch, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM guy.jones@nih.gov
OI mehta, minesh/0000-0002-4812-5713
FU Intramural NIH HHS [Z99 CA999999]
NR 128
TC 3
Z9 4
U1 2
U2 7
PU CIG MEDIA GROUP, LP
PI DALLAS
PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA
SN 1525-7304
EI 1938-0690
J9 CLIN LUNG CANCER
JI Clin. Lung Cancer
PD NOV
PY 2015
VL 16
IS 6
BP 413
EP 430
DI 10.1016/j.cllc.2015.04.001
PG 18
WC Oncology
SC Oncology
GA CU1GD
UT WOS:000363267500019
PM 26027433
ER
PT J
AU Potter, WZ
AF Potter, W. Z.
TI Biomarkers of Brain Structure and Function for Neurodegenerative
Disorders: Are They Adequate for Go/No Go Decisions in Drug Development?
SO CLINICAL PHARMACOLOGY & THERAPEUTICS
LA English
DT Editorial Material
AB Given the high risk of developing drugs for neurodegenerative diseases if post-phase I decisions to go into efficacy studies were made with quantitative knowledge of an agent's action in brain, the risks should be diminished. Furthermore, if biomarkers were compelling, they could be utilized during a lengthy trial as an early measure of futility. What follows is one perspective on the adequacy of current and emerging measures to be applied to such decision making.
C1 NIMH, Bethesda, MD 20892 USA.
RP Potter, WZ (reprint author), NIMH, Bethesda, MD 20892 USA.
EM bill.potter@nih.gov
NR 9
TC 2
Z9 2
U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0009-9236
EI 1532-6535
J9 CLIN PHARMACOL THER
JI Clin. Pharmacol. Ther.
PD NOV
PY 2015
VL 98
IS 5
BP 472
EP 474
DI 10.1002/cpt.196
PG 3
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA CU3DU
UT WOS:000363405000011
PM 26418882
ER
PT J
AU Mahnke, YD
Beddall, MH
Roederer, M
AF Mahnke, Yolanda D.
Beddall, Margaret H.
Roederer, Mario
TI OMIP-029: Human NK-cell phenotypization
SO CYTOMETRY PART A
LA English
DT Article
DE NK cells; immunophenotyping; NK receptors; FcR receptors
ID NATURAL-KILLER-CELLS; RECEPTOR
C1 [Mahnke, Yolanda D.; Beddall, Margaret H.; Roederer, Mario] NIAID, ImmunoTechnol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
RP Mahnke, YD (reprint author), NIAID, ImmunoTechnol Sect, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM yolanda.mahnke@gmail.com
NR 10
TC 1
Z9 1
U1 0
U2 0
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 NOV
PY 2015
VL 87A
IS 11
BP 986
EP 988
DI 10.1002/cyto.a.22728
PG 3
WC Biochemical Research Methods; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA CU1FS
UT WOS:000363266200005
PM 26228006
ER
PT J
AU Bassig, BA
Cerhan, JR
Au, WY
Kim, HN
Sangrajrang, S
Hu, W
Tse, J
Berndt, S
Zheng, TZ
Zhang, HP
Pornsopone, P
Lee, JJ
Kim, HJ
Skibola, CF
Vijai, J
Burdette, L
Yeager, M
Brennan, P
Shin, MH
Liang, R
Chanock, S
Lan, Q
Rothman, N
AF Bassig, Bryan A.
Cerhan, James R.
Au, Wing-Yan
Kim, Hee Nam
Sangrajrang, Suleeporn
Hu, Wei
Tse, Jovic
Berndt, Sonja
Zheng, Tongzhang
Zhang, Heping
Pornsopone, Pattarapong
Lee, Je-Jung
Kim, Hyeoung-Joon
Skibola, Christine F.
Vijai, Joseph
Burdette, Laurie
Yeager, Meredith
Brennan, Paul
Shin, Min-Ho
Liang, Raymond
Chanock, Stephen
Lan, Qing
Rothman, Nathaniel
TI Genetic susceptibility to diffuse large B-cell lymphoma in a pooled
study of three Eastern Asian populations
SO EUROPEAN JOURNAL OF HAEMATOLOGY
LA English
DT Article
DE Diffuse large B-cell lymphoma; Eastern Asians; lymphoma; genetic
susceptibility to DLBCL
ID GENOME-WIDE ASSOCIATION; HEALTH-ORGANIZATION CLASSIFICATION;
NON-HODGKIN-LYMPHOMA; CHINESE POPULATION; NEOPLASMS; THAILAND; RISK;
LOCI
AB ObjectivesDiffuse large B-cell lymphoma (DLBCL) is an aggressive subtype of non-Hodgkin lymphoma (NHL) and is the most common NHL subtype diagnosed worldwide. The first large-scale genome-wide association study (GWAS) of DLBCL with over 4000 cases conducted among individuals of European ancestry recently identified five independent SNPs that achieved genome-wide significance, and two SNPs that showed a suggestive association with DLBCL risk.
MethodsTo evaluate whether Eastern Asians and individuals of European ancestry share similar genetic risk factors for this disease, we attempted to replicate these GWAS findings in a pooled series of 1124 DLBCL cases and 3596 controls from Hong Kong, South Korea, and Thailand.
ResultsThree of the five genome-wide significant SNPs from the DLBCL GWAS were significantly associated with DLBCL in our study population, including the top finding from the GWAS, EXOC2 rs116446171, which achieved genome-wide significance in our data (per allele OR=2.04, 95% CI=1.63-2.56; p(trend)=3.9x10(-10)). Additionally, we observed a significant association with PVT1 rs13255292 (per allele OR=1.34, 95% CI=1.19-1.52; p(trend)=2.1x10(-6)), which was the second strongest finding in the GWAS, and with HLA-B rs2523607 (per allele OR=3.05, 95% CI=1.32-7.05; p(trend)=0.009).
ConclusionsOur study, which provides the first evaluation in Eastern Asians of SNPs definitively associated with DLBCL risk in individuals of European ancestry, indicates that at least some of the genetic factors associated with risk of DLBCL are similar between these populations.
C1 [Bassig, Bryan A.; Hu, Wei; Berndt, Sonja; Burdette, Laurie; Yeager, Meredith; Chanock, Stephen; Lan, Qing; Rothman, Nathaniel] NCI, Div Canc Epidemiol & Genet, DHHS, NIH, Bethesda, MD 20892 USA.
[Cerhan, James R.] Mayo Clin, Div Epidemiol, Rochester, MN USA.
[Au, Wing-Yan; Tse, Jovic; Liang, Raymond] Univ Hong Kong, Queen Mary Hosp, Dept Med, Hong Kong, Hong Kong, Peoples R China.
[Kim, Hee Nam; Kim, Hyeoung-Joon] Chonnam Natl Univ, Hwasun Hosp, Genome Res Ctr Hematopoiet Dis, Hwasun, Jeollanam Do, South Korea.
[Kim, Hee Nam; Shin, Min-Ho] Chonnam Natl Univ, Ctr Creat Biomed Scientists, Gwangju, South Korea.
[Sangrajrang, Suleeporn] Natl Canc Inst, Div Res, Bangkok, Thailand.
[Zheng, Tongzhang; Zhang, Heping] Yale Univ, Sch Publ Hlth, New Haven, CT USA.
[Pornsopone, Pattarapong] Natl Canc Inst, Dept Med Oncol, Bangkok, Thailand.
[Lee, Je-Jung; Kim, Hyeoung-Joon] Chonnam Natl Univ, Sch Med, Res Inst Med Sci, Dept Hematol Oncol, Gwangju, South Korea.
[Skibola, Christine F.] Univ Alabama Birmingham, Sch Publ Hlth, Dept Epidemiol, Birmingham, AL 35294 USA.
[Vijai, Joseph] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA.
[Burdette, Laurie; Yeager, Meredith] NCI, Canc Genom Res Lab, DHHS, NIH, Gaithersburg, MD USA.
[Brennan, Paul] IARC, Genet Epidemiol Grp, Lyon, France.
[Shin, Min-Ho] Chonnam Natl Univ, Sch Med, Dept Prevent Med, Gwangju, South Korea.
RP Bassig, BA (reprint author), NCI, Div Canc Epidemiol & Genet, DHHS, NIH, 9609 Med Ctr Dr MSC 9776,Room 6E634, Bethesda, MD 20892 USA.
EM bryan.bassig@mail.nih.gov
OI Joseph, Vijai/0000-0002-7933-151X
FU Intramural Research Program of the NIH; NCI; National Project for
Personalized Genomic Medicine, Ministry for Health & Welfare, Republic
of Korea [A111218-11-GM06]; NCI (Thailand); Ministry of Public Health;
Hong Kong University Carol Chau Ting Tong Research Fund; Leading Foreign
Research Institute Recruitment Program through the National Research
Foundation of Korea (NRF) - Ministry of Education, Science and
Technology (MEST) [NRF-2011-0030034]
FX Supported in part by the Intramural Research Program of the NIH, NCI, a
grant from the National Project for Personalized Genomic Medicine,
Ministry for Health & Welfare, Republic of Korea (A111218-11-GM06), the
NCI (Thailand), Ministry of Public Health, and the Hong Kong University
Carol Chau Ting Tong Research Fund. This research was also supported by
the Leading Foreign Research Institute Recruitment Program through the
National Research Foundation of Korea (NRF), funded by the Ministry of
Education, Science and Technology (MEST) (NRF-2011-0030034). We would
like to thank all participants in these studies.
NR 15
TC 4
Z9 4
U1 2
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0902-4441
EI 1600-0609
J9 EUR J HAEMATOL
JI Eur. J. Haematol.
PD NOV
PY 2015
VL 95
IS 5
BP 442
EP 448
DI 10.1111/ejh.12513
PG 7
WC Hematology
SC Hematology
GA CU2CD
UT WOS:000363328800009
PM 25611436
ER
PT J
AU Shah, RV
Murthy, VL
Abbasi, SA
Eng, J
Wu, CL
Ouyang, P
Kwong, RY
Goldfine, A
Bluemke, DA
Lima, J
Jerosch-Herold, M
AF Shah, Ravi V.
Murthy, Venkatesh L.
Abbasi, Siddique A.
Eng, John
Wu, Colin
Ouyang, Pamela
Kwong, Raymond Y.
Goldfine, Allison
Bluemke, David A.
Lima, Joao
Jerosch-Herold, Michael
TI Weight loss and progressive left ventricular remodelling: The
Multi-Ethnic Study of Atherosclerosis (MESA)
SO EUROPEAN JOURNAL OF PREVENTIVE CARDIOLOGY
LA English
DT Article
DE Obesity; cardiac magnetic resonance; weight loss
ID INCIDENT CARDIOVASCULAR EVENTS; WHITE ADULT MEN; BARIATRIC SURGERY;
OBESITY CARDIOMYOPATHY; INSULIN-RESISTANCE; RISK-FACTORS; MASS;
GEOMETRY; DISEASE; IMPACT
AB Aims Impact of weight loss on cardiac structure has not been extensively investigated in large, multi-ethnic, community-based populations. We investigated the longitudinal impact of weight loss on cardiac structure by cardiac magnetic resonance (CMR).
Methods and results 2351 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) who underwent CMR at Exam 1 (2002) and Exam 5 (2011) were included. Primary outcomes were percentage change in LV mass (indexed to height) and LV mass-to-volume ratio (concentric LV remodelling). Multivariable linear regression was used to measure the association between outcomes and weight change. At median 9.4 years' follow-up, 639 individuals (27%) experienced >5% weight loss (median 6.9kg) and 511 (22%) had >5% weight gain (median 6.4kg). A >5% weight gain was associated with the greatest increase in LV mass (+5.4% median) and LV mass-to-volume ratio (+12.2% median). Adjusting for medications, hypertension/diabetes (and change in these risk factors), age, race and other risk factors, every 5% weight loss was associated with a 1.3% decrease in height-indexed LV mass and 1.3% decrease in LV mass-to-volume ratio (p<0.0001). There was no effect modification/confounding by age, race, gender or baseline BMI. Change in LV mass-to-volume ratio was roughly linear, specifically for modest degrees of weight loss (-10% to +10%). Change in LV mass was linear with weight loss, suggesting no threshold of weight loss is needed for LV mass regression.
Conclusions In a large multi-ethnic population, weight loss is associated with beneficial effects on cardiac structure, independent of age, race, gender, BMI and obesity-related cardiometabolic risk. There is no threshold of weight loss required to produce these effects.
C1 [Shah, Ravi V.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA.
[Murthy, Venkatesh L.] Univ Michigan, Dept Med, Div Cardiovasc Med, Ann Arbor, MI 48109 USA.
[Murthy, Venkatesh L.] Univ Michigan, Dept Radiol, Div Nucl Med, Ann Arbor, MI 48109 USA.
[Murthy, Venkatesh L.] Univ Michigan, Dept Radiol, Cardiothorac Imaging Div, Ann Arbor, MI 48109 USA.
[Abbasi, Siddique A.; Kwong, Raymond Y.; Jerosch-Herold, Michael] Brigham & Womens Hosp, Noninvas Cardiovasc Imaging, Boston, MA 02115 USA.
[Eng, John; Wu, Colin] NHLBI, Off Biostat Res, Bethesda, MD 20892 USA.
[Ouyang, Pamela] Johns Hopkins Bayview Med Ctr, Div Cardiol, Baltimore, MD USA.
[Goldfine, Allison] Joslin Diabet Ctr, Boston, MA 02215 USA.
[Bluemke, David A.] Natl Inst Biomed Imaging & Bioengn, Radiol & Imaging Sci, NIH, Ctr Clin, Bethesda, MD USA.
[Lima, Joao] Johns Hopkins Med Ctr, Dept Cardiol & Med, Baltimore, MD USA.
RP Jerosch-Herold, M (reprint author), Brigham & Womens Hosp, Dept Radiol, 75 Francis St,L1-RA050, Boston, MA 02115 USA.
EM mjerosch-herold@partners.org
RI Murthy, Venkatesh/B-3448-2013;
OI Murthy, Venkatesh/0000-0002-7901-1321; Bluemke,
David/0000-0002-8323-8086
FU National Heart, Lung, and Blood Institute [NO1-HC-95159, NO1-HC-95160,
NO1-HC-95161, NO1-HC-95162, NO1-HC-95163, NO1-HC-95164, NO1-HC-95165,
NO1-HC-95166, NO1-HC-95167, NO1-HC-95168, N01-HC-95169]; American Heart
Association Post-Doctoral Fellowship Award [11POST000002]; Heart Failure
National Institutes of Health Clinical Research Network [U01-HL084877];
[R01-HL-65580]
FX MESA is supported by contracts NO1-HC-95159 to N01-HC-95169 from the
National Heart, Lung, and Blood Institute. Dr Shah was supported by an
American Heart Association Post-Doctoral Fellowship Award (11POST000002)
and a training grant from the Heart Failure National Institutes of
Health Clinical Research Network (U01-HL084877). Dr Jerosch-Herold
receives support through R01-HL-65580. All other authors have no
financial disclosures relevant to the content of this manuscript.
NR 31
TC 2
Z9 2
U1 0
U2 2
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 2047-4873
EI 2047-4881
J9 EUR J PREV CARDIOL
JI Eur. J. Prev. Cardiol.
PD NOV
PY 2015
VL 22
IS 11
BP 1408
EP 1418
DI 10.1177/2047487314541731
PG 11
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA CT7LE
UT WOS:000362995400005
PM 25009171
ER
PT J
AU Bailey-Wilson, JE
Simpson, CL
Musolf, AM
Pinney, SM
De Andrade, M
Gaba, CR
Yang, P
You, M
Schwartz, AG
Mandal, D
Liu, YH
Spitz, MR
Kupert, EY
Amos, CI
Anderson, M
AF Bailey-Wilson, Joan E.
Simpson, Claire L.
Musolf, Anthony M.
Pinney, Susan M.
De Andrade, Mariza
Gaba, Colette R.
Yang, Ping
You, Ming
Schwartz, Ann G.
Mandal, Diptasri
Liu, Yanhong
Spitz, Margaret R.
Kupert, Elena Y.
Amos, Christopher I.
Anderson, MarshallW.
TI Linkage methods used to evaluate EYA4 as a candidate risk locus in GELCC
familial lung cancer families linked to 6q
SO GENETIC EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the International-Genetic-Epidemiology-Society (IGES)
CY OCT 04-06, 2015
CL Baltimore, MD
SP Int Genet Epidemiol Soc
C1 [Bailey-Wilson, Joan E.; Simpson, Claire L.; Musolf, Anthony M.] NHGRI, NIH, Baltimore, MD USA.
[Pinney, Susan M.] Univ Cincinnati, Coll Med, Cincinnati, OH USA.
[De Andrade, Mariza; Yang, Ping] Mayo Clin, Rochester, MN USA.
[Gaba, Colette R.] Univ Toledo, Dana Canc Ctr, Toledo, OH 43606 USA.
[You, Ming] Med Coll Wisconsin, Milwaukee, WI 53226 USA.
[Schwartz, Ann G.] Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA.
[Mandal, Diptasri] Louisiana State Univ, Hlth Sci Ctr, New Orleans, LA USA.
[Liu, Yanhong; Spitz, Margaret R.] Baylor Coll Med, Houston, TX 77030 USA.
[Kupert, Elena Y.; Anderson, MarshallW.] Med Coll Wisconsin, Milwaukee, WI 53226 USA.
[Amos, Christopher I.] Dartmouth Coll, Geisel Sch Med, Lebanon, NH 03756 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
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 NOV
PY 2015
VL 39
IS 7
MA 8
BP 531
EP 532
PG 2
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA CU2FZ
UT WOS:000363340500012
ER
PT J
AU Bureau, A
Sampson, J
Yanek, LR
Mathias, R
Ruczinski, I
AF Bureau, Alexandre
Sampson, Joshua
Yanek, Lisa R.
Mathias, Rasika
Ruczinski, Ingo
TI Extension of a rare variant sharing exact test to sharing patterns
involving a subset of affected relatives
SO GENETIC EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the International-Genetic-Epidemiology-Society (IGES)
CY OCT 04-06, 2015
CL Baltimore, MD
SP Int Genet Epidemiol Soc
C1 [Bureau, Alexandre] Univ Laval, Quebec City, PQ G1K 7P4, Canada.
[Sampson, Joshua] NCI, Bethesda, MD 20892 USA.
[Yanek, Lisa R.; Mathias, Rasika] Johns Hopkins Univ, Sch Med, Baltimore, MD 21218 USA.
[Ruczinski, Ingo] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0741-0395
EI 1098-2272
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD NOV
PY 2015
VL 39
IS 7
MA 19
BP 536
EP 536
PG 1
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA CU2FZ
UT WOS:000363340500023
ER
PT J
AU Chen, F
Szymanski, EP
Olivier, KN
Liu, XY
Tettelin, H
Holland, SM
Duggal, P
AF Chen, Fei
Szymanski, Eva P.
Olivier, Kenneth N.
Liu, Xinyue
Tettelin, Herve
Holland, Steven M.
Duggal, Priya
TI Whole exome sequencing and linkage analysis of patients with pulmonary
nontuberculous mycobacterial infection
SO GENETIC EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the International-Genetic-Epidemiology-Society (IGES)
CY OCT 04-06, 2015
CL Baltimore, MD
SP Int Genet Epidemiol Soc
C1 [Chen, Fei; Duggal, Priya] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Szymanski, Eva P.; Holland, Steven M.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
[Olivier, Kenneth N.] NHLBI, Cardiovasc & Pulm Branch, NIH, Bethesda, MD 20892 USA.
[Liu, Xinyue; Tettelin, Herve] Univ Maryland, Sch Med, Inst Genome Sci, Baltimore, MD 21201 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0741-0395
EI 1098-2272
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD NOV
PY 2015
VL 39
IS 7
MA 22
BP 537
EP 537
PG 1
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA CU2FZ
UT WOS:000363340500026
ER
PT J
AU Chen, H
Wang, CL
Conomos, MP
Stilp, AM
Li, ZL
Sofer, T
Szpiro, AA
Chen, W
Brehm, JM
Celedon, JC
Redline, SS
Papanicolaou, GJ
Thornton, TA
AF Chen, Han
Wang, Chaolong
Conomos, Matthew P.
Stilp, Adrienne M.
Li, Zilin
Sofer, Tamar
Szpiro, Adam A.
Chen, Wei
Brehm, John M.
Celedon, Juan C.
Redline, Susan S.
Papanicolaou, George J.
Thornton, Timothy A.
TI GMMAT: logistic mixed models to control for population stratification
and relatedness in genetic association studies with binary traits
SO GENETIC EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the International-Genetic-Epidemiology-Society (IGES)
CY OCT 04-06, 2015
CL Baltimore, MD
SP Int Genet Epidemiol Soc
C1 [Chen, Han; Li, Zilin] Harvard Univ, TH Chan Sch Publ Hlth, Cambridge, MA 02138 USA.
[Wang, Chaolong] Genome Inst Singapore, Singapore, Singapore.
[Conomos, Matthew P.; Stilp, Adrienne M.; Sofer, Tamar; Szpiro, Adam A.; Thornton, Timothy A.] Univ Washington, Seattle, WA 98195 USA.
[Chen, Wei; Brehm, John M.; Celedon, Juan C.] Childrens Hosp Pittsburgh, Pittsburgh, PA USA.
[Redline, Susan S.] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Papanicolaou, George J.] NHLBI, Bethesda, MD USA.
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 0741-0395
EI 1098-2272
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD NOV
PY 2015
VL 39
IS 7
MA 23
BP 537
EP 537
PG 1
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA CU2FZ
UT WOS:000363340500027
ER
PT J
AU Childs, EJ
Chaffee, KG
Gallinger, S
Syngal, S
Schwartz, AG
Cote, ML
Bondy, M
Goggins, MG
Hruban, RH
Chanock, S
Hoover, R
Fuchs, C
Rider, DN
Amundadottir, L
Stolzenberg-Solomon, R
Wolpin, B
Risch, HA
Petersen, GM
Klein, AP
AF Childs, Erica J.
Chaffee, Kari G.
Gallinger, Steven
Syngal, Sapna
Schwartz, Ann G.
Cote, Michele L.
Bondy, Melissa
Goggins, Michael G.
Hruban, Ralph H.
Chanock, Stephen
Hoover, Robert
Fuchs, Charles
Rider, David N.
Amundadottir, Laufey
Stolzenberg-Solomon, Rachael
Wolpin, Brian
Risch, Harvey A.
Petersen, Gloria M.
Klein, Alison P.
TI Examination of established cancer risk variants in putatively high-risk
pancreatic cancer patients: A PACGENE study
SO GENETIC EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the International-Genetic-Epidemiology-Society (IGES)
CY OCT 04-06, 2015
CL Baltimore, MD
SP Int Genet Epidemiol Soc
C1 [Childs, Erica J.] Johns Hopkins Sch Med, Kimmel Comprehens Canc Ctr, Dept Oncol, Baltimore, MD USA.
[Chaffee, Kari G.; Rider, David N.; Petersen, Gloria M.] Mayo Clin, Coll Med, Dept Hlth Sci Res, Rochester, MN USA.
[Gallinger, Steven] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada.
[Syngal, Sapna] Brigham & Womens Hosp, Dana Farber Canc Inst, Div Populat Sci, Boston, MA 02115 USA.
[Syngal, Sapna] Brigham & Womens Hosp, Div Gastroenterol, Boston, MA 02115 USA.
[Schwartz, Ann G.; Cote, Michele L.] Karmanos Canc Inst, Dept Oncol, Detroit, MI USA.
[Schwartz, Ann G.; Cote, Michele L.] Wayne State Univ, Detroit, MI USA.
[Bondy, Melissa] Baylor Coll Med, Dan L Duncan Canc Ctr, Houston, TX 77030 USA.
[Goggins, Michael G.; Hruban, Ralph H.] Johns Hopkins Sch Med, Sol Goldman Pancreat Canc Res Ctr, Dept Pathol, Baltimore, MD USA.
[Chanock, Stephen; Hoover, Robert; Amundadottir, Laufey] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Fuchs, Charles; Wolpin, Brian] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Fuchs, Charles] Brigham & Womens Hosp, Dept Med, Channing Div Network Med, Boston, MA 02115 USA.
[Fuchs, Charles; Wolpin, Brian] Harvard Univ, Sch Med, Boston, MA USA.
[Stolzenberg-Solomon, Rachael] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA.
[Wolpin, Brian] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA.
[Risch, Harvey A.] Yale Univ, Sch Publ Hlth, New Haven, CT USA.
[Klein, Alison P.] Johns Hopkins Sch Med, Sidney Kimmel Comprehens Canc Ctr, Dept Oncol, Baltimore, MD USA.
[Klein, Alison P.] Johns Hopkins Sch Med, Sol Goldman Pancreat Canc Res Ctr, Dept Pathol, Baltimore, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0741-0395
EI 1098-2272
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD NOV
PY 2015
VL 39
IS 7
MA 27
BP 538
EP 539
PG 2
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA CU2FZ
UT WOS:000363340500031
ER
PT J
AU Chiu, CY
Jung, J
Weeks, D
Wilson, AF
Bailey-Wilson, J
Amos, CI
Xiong, MM
Mills, J
Fan, RZ
AF Chiu, Chi-Yang
Jung, Jeesun
Weeks, Daniel
Wilson, Alexander F.
Bailey-Wilson, Joan
Amos, Christopher I.
Xiong, Momiao
Mills, James
Fan, Ruzong
TI A Comparison Study of Fixed and Mixed Effect Models for Gene Level
Association Studies of Complex Traits
SO GENETIC EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the International-Genetic-Epidemiology-Society (IGES)
CY OCT 04-06, 2015
CL Baltimore, MD
SP Int Genet Epidemiol Soc
C1 [Chiu, Chi-Yang; Mills, James; Fan, Ruzong] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
[Jung, Jeesun] NIAAA, NIH, Bethesda, MD USA.
[Weeks, Daniel] Univ Pittsburgh, Pittsburgh, PA 15260 USA.
[Wilson, Alexander F.; Bailey-Wilson, Joan] NHGRI, NIH, Bethesda, MD USA.
[Amos, Christopher I.] Dartmouth Coll, Geisel Sch Med, Hanover, NH 03755 USA.
[Xiong, Momiao] Univ Texas Houston, Houston, TX USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0741-0395
EI 1098-2272
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD NOV
PY 2015
VL 39
IS 7
MA 28
BP 539
EP 539
PG 1
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA CU2FZ
UT WOS:000363340500032
ER
PT J
AU Fan, RZ
Amos, CI
Wang, YF
Weeks, D
Li, Y
Ren, HB
Lobach, I
Xiong, MM
Moore, JH
Boehnke, M
AF Fan, Ruzong
Amos, Christopher I.
Wang, Yifan
Weeks, Daniel
Li, Yun
Ren, Haobo
Lobach, Iryna
Xiong, Momiao
Moore, Jason H.
Boehnke, Michael
TI Meta-analysis of Complex Diseases at Gene Level by Functional Regression
Models
SO GENETIC EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the International-Genetic-Epidemiology-Society (IGES)
CY OCT 04-06, 2015
CL Baltimore, MD
SP Int Genet Epidemiol Soc
C1 [Fan, Ruzong] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Rockville, MD USA.
[Amos, Christopher I.; Moore, Jason H.] Univ Dartmouth, Hanover, NH USA.
[Wang, Yifan] FDA, Silver Spring, MD USA.
[Weeks, Daniel] Univ Pittsburgh, Pittsburgh, PA 15260 USA.
[Li, Yun] Univ N Carolina, Chapel Hill, NC 27515 USA.
[Ren, Haobo] Regeneron Pharmaceut Inc, Tarrytown, NY USA.
[Lobach, Iryna] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Xiong, Momiao] Univ Texas Houston, Houston, TX USA.
[Boehnke, Michael] Univ Michigan, Ann Arbor, MI 48109 USA.
NR 0
TC 0
Z9 0
U1 2
U2 4
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 NOV
PY 2015
VL 39
IS 7
MA 49
BP 547
EP 548
PG 2
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA CU2FZ
UT WOS:000363340500053
ER
PT J
AU Goldin, LR
Rotunno, M
McMaster, ML
Yeager, M
Hicks, BD
Burdette, L
Goldstein, AM
Fontaine, L
Tucker, MA
Marti, GE
Chanock, SJ
Caporaso, NE
AF Goldin, Lynn R.
Rotunno, Melissa
McMaster, Mary L.
Yeager, Meredith
Hicks, Belynda D.
Burdette, Laurie
Goldstein, Alisa M.
Fontaine, Laura
Tucker, Margaret A.
Marti, Gerald E.
Chanock, Stephen J.
Caporaso, Neil E.
TI Whole exome sequencing in high-risk chronic lymphocytic leukemia
families: do rare germline variants in somatically altered genes or GWAS
genes contribute to susceptibility?
SO GENETIC EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the International-Genetic-Epidemiology-Society (IGES)
CY OCT 04-06, 2015
CL Baltimore, MD
SP Int Genet Epidemiol Soc
C1 [Goldin, Lynn R.; Rotunno, Melissa; McMaster, Mary L.; Goldstein, Alisa M.; Caporaso, Neil E.] NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Yeager, Meredith; Hicks, Belynda D.; Burdette, Laurie] NCI, Canc Genom Res Lab, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Fontaine, Laura] Westat Corp, Rockville, MD USA.
[Tucker, Margaret A.] NCI, Human Genet Program, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Marti, Gerald E.] NHLBI, NIH, Bethesda, MD 20892 USA.
[Chanock, Stephen J.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0741-0395
EI 1098-2272
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD NOV
PY 2015
VL 39
IS 7
MA 62
BP 553
EP 553
PG 1
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA CU2FZ
UT WOS:000363340500066
ER
PT J
AU Goldstein, AM
Fraser, MC
Yang, XHR
Tucker, MA
AF Goldstein, Alisa M.
Fraser, Mary C.
Yang, Xiaohong R.
Tucker, Margaret A.
TI Gene discovery obstacles in familial melanoma, a complex disease
SO GENETIC EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the International-Genetic-Epidemiology-Society (IGES)
CY OCT 04-06, 2015
CL Baltimore, MD
SP Int Genet Epidemiol Soc
C1 [Goldstein, Alisa M.; Fraser, Mary C.; Yang, Xiaohong R.; Tucker, Margaret A.] NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0741-0395
EI 1098-2272
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD NOV
PY 2015
VL 39
IS 7
MA 63
BP 553
EP 554
PG 2
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA CU2FZ
UT WOS:000363340500067
ER
PT J
AU Holzinger, ER
Malley, J
Li, Q
Bailey-Wilson, JE
AF Holzinger, Emily R.
Malley, James
Li, Qing
Bailey-Wilson, Joan E.
TI r2VIM: A variable selection method for identifying complex genetic
models associated with human traits
SO GENETIC EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the International-Genetic-Epidemiology-Society (IGES)
CY OCT 04-06, 2015
CL Baltimore, MD
SP Int Genet Epidemiol Soc
C1 [Holzinger, Emily R.; Li, Qing; Bailey-Wilson, Joan E.] NHGRI, NIH, Baltimore, MD USA.
[Malley, James] NIH, Ctr Informat Technol, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0741-0395
EI 1098-2272
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD NOV
PY 2015
VL 39
IS 7
MA 70
BP 556
EP 556
PG 1
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA CU2FZ
UT WOS:000363340500074
ER
PT J
AU Li, Q
Holzinger, E
Hetmanski, JB
Marazita, ML
Beaty, TH
Bailey-Wilson, JE
AF Li, Qing
Holzinger, Emily
Hetmanski, Jacqueline B.
Marazita, Mary L.
Beaty, Terri H.
Bailey-Wilson, Joan E.
TI Modified Random Forest Algorithm to Identify gene-gene Interaction in
Case-Parent Trios Studies of Oral Cleft
SO GENETIC EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the International-Genetic-Epidemiology-Society (IGES)
CY OCT 04-06, 2015
CL Baltimore, MD
SP Int Genet Epidemiol Soc
C1 [Li, Qing; Holzinger, Emily; Bailey-Wilson, Joan E.] NHGRI, Computat & Stat Genom Branch, NIH, Baltimore, MD USA.
[Hetmanski, Jacqueline B.; Marazita, Mary L.; Beaty, Terri H.] Johns Hopkins Univ, Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
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 NOV
PY 2015
VL 39
IS 7
MA 92
BP 563
EP 564
PG 2
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA CU2FZ
UT WOS:000363340500096
ER
PT J
AU Mechanic, LE
Lindstrom, S
Chen, HS
Daily, K
Feuer, EJ
Green, T
Hodgson, J
Kaefer, CM
Kern, A
McTigue, K
Norman, T
Sieberts, S
Wellons, A
Gillanders, EM
AF Mechanic, Leah E.
Lindstroem, Sara
Chen, Huann-Sheng
Daily, Kenneth
Feuer, Eric J.
Green, Tiffany
Hodgson, Jay
Kaefer, Christine M.
Kern, Anna
McTigue, Kevin
Norman, Thea
Sieberts, Solly
Wellons, Audrey
Gillanders, Elizabeth M.
TI Up For A Challenge (U4C) - Stimulating Innovation in Breast Cancer
Genetic Epidemiology
SO GENETIC EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the International-Genetic-Epidemiology-Society (IGES)
CY OCT 04-06, 2015
CL Baltimore, MD
SP Int Genet Epidemiol Soc
C1 [Mechanic, Leah E.; Chen, Huann-Sheng; Feuer, Eric J.; Green, Tiffany; Kaefer, Christine M.; Kern, Anna; McTigue, Kevin; Wellons, Audrey; Gillanders, Elizabeth M.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Lindstroem, Sara] Harvard Univ, TH Chan Sch Publ Hlth, Cambridge, MA 02138 USA.
[Daily, Kenneth; Hodgson, Jay; Norman, Thea; Sieberts, Solly] Sage Bionetworks, Seattle, WA USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0741-0395
EI 1098-2272
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD NOV
PY 2015
VL 39
IS 7
MA 106
BP 568
EP 569
PG 2
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA CU2FZ
UT WOS:000363340500110
ER
PT J
AU Musolf, A
Simpson, CL
Pinney, SM
de Andrade, M
Gaba, C
Yang, P
You, M
Schwartz, AG
Mandal, D
Kupert, EY
Amos, CI
Anderson, MW
Bailey-Wilson, JE
AF Musolf, Anthony
Simpson, Claire L.
Pinney, Susan M.
de Andrade, Mariza
Gaba, Collette
Yang, Ping
You, Ming
Schwartz, Ann G.
Mandal, Diptasri
Kupert, Elena Y.
Amos, Christopher I.
Anderson, Marshall W.
Bailey-Wilson, Joan E.
TI Reproducibility in MCMC-based Linkage Analyses using Dense Marker Maps
SO GENETIC EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the International-Genetic-Epidemiology-Society (IGES)
CY OCT 04-06, 2015
CL Baltimore, MD
SP Int Genet Epidemiol Soc
C1 [Musolf, Anthony; Simpson, Claire L.; Bailey-Wilson, Joan E.] NHGRI, NIH, Baltimore, MD USA.
[Pinney, Susan M.] Univ Cincinnati, Coll Med, Cincinnati, OH USA.
[de Andrade, Mariza; Yang, Ping] Mayo Clin, Rochester, MN USA.
[Gaba, Collette] Univ Toledo, Dana Canc Ctr, Toledo, OH 43606 USA.
[You, Ming; Kupert, Elena Y.; Anderson, Marshall W.] Med Coll Wisconsin, Milwaukee, WI 53226 USA.
[Schwartz, Ann G.] Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA.
[Mandal, Diptasri] Louisiana State Univ, Hlth Sci Ctr, New Orleans, LA USA.
[Amos, Christopher I.] Dartmouth Coll, Geisel Sch Med, Lebanon, NH 03756 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0741-0395
EI 1098-2272
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD NOV
PY 2015
VL 39
IS 7
MA 114
BP 571
EP 572
PG 2
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA CU2FZ
UT WOS:000363340500118
ER
PT J
AU Sabourin, JA
Sorant, AJM
Wilson, AF
AF Sabourin, Jeremy A.
Sorant, Alexa J. M.
Wilson, Alexander F.
TI Getting the most from your data: Comparing analyses using qualitative
traits and related quantitative traits
SO GENETIC EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the International-Genetic-Epidemiology-Society (IGES)
CY OCT 04-06, 2015
CL Baltimore, MD
SP Int Genet Epidemiol Soc
C1 [Sabourin, Jeremy A.; Sorant, Alexa J. M.; Wilson, Alexander F.] NHGRI, Genometr Sect, Computat & Stat Genom Branch, NIH, Baltimore, MD USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0741-0395
EI 1098-2272
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD NOV
PY 2015
VL 39
IS 7
MA 127
BP 577
EP 577
PG 1
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA CU2FZ
UT WOS:000363340500131
ER
PT J
AU Schwantes-An, TH
Sung, H
Justice, CM
Wilson, AF
AF Schwantes-An, Tae-Hwi
Sung, Heejong
Justice, Cristina M.
Wilson, Alexander F.
TI No such thing as a free lunch: Assessing consistency of genotype
imputation
SO GENETIC EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the International-Genetic-Epidemiology-Society (IGES)
CY OCT 04-06, 2015
CL Baltimore, MD
SP Int Genet Epidemiol Soc
C1 [Schwantes-An, Tae-Hwi; Sung, Heejong; Justice, Cristina M.; Wilson, Alexander F.] NHGRI, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0741-0395
EI 1098-2272
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD NOV
PY 2015
VL 39
IS 7
MA 131
BP 578
EP 578
PG 1
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA CU2FZ
UT WOS:000363340500135
ER
PT J
AU Schwender, H
Li, Q
Neumann, C
Taub, MA
Younkin, SG
Berger, P
Scharpf, RB
Beaty, TH
Ruczinski, I
AF Schwender, Holger
Li, Qing
Neumann, Christoph
Taub, Margaret A.
Younkin, Samuel G.
Berger, Philipp
Scharpf, Robert B.
Beaty, Terri H.
Ruczinski, Ingo
TI Analyzing case-parent trio data with the R package trio
SO GENETIC EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the International-Genetic-Epidemiology-Society (IGES)
CY OCT 04-06, 2015
CL Baltimore, MD
SP Int Genet Epidemiol Soc
C1 [Schwender, Holger; Berger, Philipp] Univ Dusseldorf, Math Inst, Dusseldorf, Germany.
[Li, Qing] NHGRI, Inherited Dis Res Branch, Baltimore, MD USA.
[Neumann, Christoph] TU Dortmund Univ, Fac Stat, Dortmund, Germany.
[Taub, Margaret A.; Ruczinski, Ingo] Johns Hopkins Univ, Dept Biostat, Baltimore, MD 21205 USA.
[Younkin, Samuel G.] Univ Wisconsin, Dept Biostat & Med Informat, Madison, WI USA.
[Scharpf, Robert B.] Johns Hopkins Univ, Dept Oncol, Baltimore, MD USA.
[Beaty, Terri H.] Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0741-0395
EI 1098-2272
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD NOV
PY 2015
VL 39
IS 7
MA 132
BP 578
EP 579
PG 2
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA CU2FZ
UT WOS:000363340500136
ER
PT J
AU Sheppard, B
Benke, KS
Daniels, J
Croen, LA
Schendel, D
Ladd-Acosta, C
Fallin, MD
AF Sheppard, Brooke
Benke, Kelly S.
Daniels, Julie
Croen, Lisa A.
Schendel, Diana
Ladd-Acosta, Christine
Fallin, M. Daniele
TI Polygene - by - Prenatal Environment Interaction in Autism Spectrum
Disorder using Copy Number Variant Burden
SO GENETIC EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the International-Genetic-Epidemiology-Society (IGES)
CY OCT 04-06, 2015
CL Baltimore, MD
SP Int Genet Epidemiol Soc
C1 [Sheppard, Brooke; Ladd-Acosta, Christine] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Sheppard, Brooke; Benke, Kelly S.; Ladd-Acosta, Christine; Fallin, M. Daniele] Johns Hopkins Bloomberg Sch Publ Hlth, Wendy Klag Ctr Autism & Dev Disabil, Baltimore, MD USA.
[Sheppard, Brooke] NIH, Genet Epidemiol Res Branch, Bethesda, MD USA.
[Benke, Kelly S.; Fallin, M. Daniele] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mental Hlth, Baltimore, MD USA.
[Daniels, Julie] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27515 USA.
[Croen, Lisa A.] Kaiser Permanente No Calif, Autism Res Program, Div Res, Harbor City, CA USA.
[Schendel, Diana] Aarhus Univ, Dept Publ Hlth, Epidemiol Sect, DK-8000 Aarhus C, Denmark.
[Schendel, Diana] Aarhus Univ, Natl Ctr Register Based Res, Dept Econ & Business, DK-8000 Aarhus C, Denmark.
[Schendel, Diana] iPSYCH, Lundbeck Fdn Initiat Integrat Psychiat Res, Marion, SA, Australia.
NR 0
TC 0
Z9 0
U1 1
U2 2
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 NOV
PY 2015
VL 39
IS 7
MA 134
BP 579
EP 580
PG 2
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA CU2FZ
UT WOS:000363340500138
ER
PT J
AU Shi, M
Umbach, DM
Weinberg, CR
AF Shi, Min
Umbach, David M.
Weinberg, Clarice R.
TI Using parental phenotypes in case-parent studies
SO GENETIC EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the International-Genetic-Epidemiology-Society (IGES)
CY OCT 04-06, 2015
CL Baltimore, MD
SP Int Genet Epidemiol Soc
C1 [Shi, Min; Umbach, David M.; Weinberg, Clarice R.] Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0741-0395
EI 1098-2272
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD NOV
PY 2015
VL 39
IS 7
MA 135
BP 580
EP 580
PG 1
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA CU2FZ
UT WOS:000363340500139
ER
PT J
AU Shriner, D
Bentley, AR
Doumatey, AP
Chen, GJ
Zhou, J
Adeyemo, A
Rotimi, CN
AF Shriner, Daniel
Bentley, Amy R.
Doumatey, Ayo P.
Chen, Guanjie
Zhou, Jie
Adeyemo, Adebowale
Rotimi, Charles N.
TI Phenotypic variance explained by ancestry in admixed African Americans
SO GENETIC EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the International-Genetic-Epidemiology-Society (IGES)
CY OCT 04-06, 2015
CL Baltimore, MD
SP Int Genet Epidemiol Soc
C1 [Shriner, Daniel; Bentley, Amy R.; Doumatey, Ayo P.; Chen, Guanjie; Zhou, Jie; Adeyemo, Adebowale; Rotimi, Charles N.] NHGRI, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0741-0395
EI 1098-2272
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD NOV
PY 2015
VL 39
IS 7
MA 137
BP 580
EP 580
PG 1
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA CU2FZ
UT WOS:000363340500141
ER
PT J
AU Simpson, CL
Musolf, A
Bailey-Wilson, JE
AF Simpson, Claire L.
Musolf, Anthony
Bailey-Wilson, Joan E.
TI The Renaissance of Linkage Analysis and Effects of Extreme High Density
Genotype Data on Linkage Algorithms
SO GENETIC EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the International-Genetic-Epidemiology-Society (IGES)
CY OCT 04-06, 2015
CL Baltimore, MD
SP Int Genet Epidemiol Soc
C1 [Simpson, Claire L.; Musolf, Anthony; Bailey-Wilson, Joan E.] NHGRI, Computat & Stat Genom Branch, NIH, Baltimore, MD 21224 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0741-0395
EI 1098-2272
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD NOV
PY 2015
VL 39
IS 7
MA 138
BP 580
EP 581
PG 2
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA CU2FZ
UT WOS:000363340500142
ER
PT J
AU Sung, H
Schwantes-An, TH
Sorant, AJM
Sabourin, JA
Justice, CM
Wilson, AF
AF Sung, Heejong
Schwantes-An, Tae-Hwi
Sorant, Alexa J. M.
Sabourin, Jeremy A.
Justice, Cristina M.
Wilson, Alexander F.
TI Correlation structure of the genome
SO GENETIC EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the International-Genetic-Epidemiology-Society (IGES)
CY OCT 04-06, 2015
CL Baltimore, MD
SP Int Genet Epidemiol Soc
C1 [Sung, Heejong; Schwantes-An, Tae-Hwi; Sorant, Alexa J. M.; Sabourin, Jeremy A.; Justice, Cristina M.; Wilson, Alexander F.] NHGRI, Genometr Sect, Computat & Stat Genom Branch, NIH, Baltimore, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
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 NOV
PY 2015
VL 39
IS 7
MA 146
BP 583
EP 584
PG 2
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA CU2FZ
UT WOS:000363340500150
ER
PT J
AU Weinberg, CR
Shi, M
Wise, A
Umbach, DM
Li, LP
AF Weinberg, Clarice R.
Shi, Min
Wise, Alison
Umbach, David M.
Li, Leping
TI A stochastic search algorithm for finding multi-SNP effects using
nuclear families
SO GENETIC EPIDEMIOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the International-Genetic-Epidemiology-Society (IGES)
CY OCT 04-06, 2015
CL Baltimore, MD
SP Int Genet Epidemiol Soc
C1 [Weinberg, Clarice R.; Shi, Min; Umbach, David M.; Li, Leping] NIEHS, Res Triangle Pk, NC USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0741-0395
EI 1098-2272
J9 GENET EPIDEMIOL
JI Genet. Epidemiol.
PD NOV
PY 2015
VL 39
IS 7
MA 170
BP 592
EP 592
PG 1
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA CU2FZ
UT WOS:000363340500174
ER
PT J
AU Khalili, M
Lombardero, M
Chung, RT
Terrault, NA
Ghany, MG
Kim, WR
Lau, D
Lisker-Melman, M
Sanyal, A
Lok, AS
AF Khalili, Mandana
Lombardero, Manuel
Chung, Raymond T.
Terrault, Norah A.
Ghany, Marc G.
Kim, W. Ray
Lau, Daryl
Lisker-Melman, Mauricio
Sanyal, Arun
Lok, Anna S.
CA HBRN
TI Diabetes and prediabetes in patients with hepatitis B residing in North
America
SO HEPATOLOGY
LA English
DT Article
ID METABOLIC SYNDROME INCREASES; IMPAIRED FASTING GLUCOSE;
COUNTRY-OF-ORIGIN; BODY-MASS INDEX; VIRUS INFECTION; UNITED-STATES;
HEPATOCELLULAR-CARCINOMA; INSULIN-RESISTANCE; VIRAL-HEPATITIS; LIVER
FIBROSIS
AB Diabetes is associated with liver disease progression and increased hepatocellular carcinoma risk, but factors associated with diabetes in patients with chronic hepatitis B virus (HBV) infection in North America are unknown. We aimed to determine factors predictive of diabetes and impaired fasting glucose (IFG) in a large HBV-infected multiethnic cohort. Adults with chronic HBV not receiving antiviral therapy were enrolled from 21 centers in North America. Diabetes was defined by history/medication use or fasting glucose 126 mg/dL and IFG as fasting glucose 100-125 mg/dL. Of 882 patients included, 47.2% were female, 71.3% Asian, 83.7% foreign born, median age was 44 years, and median body mass index BMI 24.3 kg/m(2). In this cohort, 26.0% were hepatitis B envelope antigen (HBeAg) positive, 43.9% had HBV DNA 20,000 IU/mL, and 26.7% alanine aminotransferase (ALT) 2x upper limit of normal (40 U/L women, 60 U/L men). Overall, 12.5% had diabetes and 7.8% IFG. The combined prevalence of diabetes or IFG was highest among blacks (36.7%) and those either born in the United States/Canada or foreign born with migration >20 years ago (25.5%). Obesity (odds ratio [OR]: 2.13), hyperlipidemia (OR, 4.13), hypertension (OR, 3.67), high ALT level (OR, 1.86), and family history of diabetes (OR, 3.43) were associated with diabetes. Factors associated with IFG were obesity (OR, 4.13) and hypertension (OR, 3.27), but also HBeAg positivity (OR, 0.39). Recent migration was negatively associated with diabetes among non-Asians (OR, 0.30). Conclusions: Diabetes is more prevalent in HBV-infected North American adults than the general population and is associated with known metabolic risk factors and liver damage, as determined by ALT levels. Among the foreign born, longer duration of North America residence predicted diabetes risk in non-Asians. These results highlight the opportunities for interventions to prevent diabetes especially among at-risk ethnic groups with HBV. (Hepatology 2015;62:1364-1374)
C1 [Khalili, Mandana; Terrault, Norah A.] Univ Calif San Francisco, San Francisco, CA 94110 USA.
[Lombardero, Manuel] Univ Pittsburgh, Pittsburgh, PA 15260 USA.
[Chung, Raymond T.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Ghany, Marc G.] NIH, Bethesda, MD USA.
[Kim, W. Ray] Stanford Univ, Stanford, CA 94305 USA.
[Lau, Daryl] Beth Israel Deaconess Med Ctr, Boston, MA USA.
[Lisker-Melman, Mauricio] Washington Univ, Sch Med, St Louis, MO 63130 USA.
[Sanyal, Arun] Virginia Commonwealth Univ, Richmond, VA 23284 USA.
[Lok, Anna S.] Univ Michigan, Ann Arbor, MI 48109 USA.
RP Khalili, M (reprint author), Univ Calif San Francisco, San Francisco Gen Hosp, 1001 Potrero Ave,NH-3D, San Francisco, CA 94110 USA.
EM Mandana.Khalili@ucsf.edu
OI Cloonan, Yona/0000-0003-3893-3693; Wahed, Abdus/0000-0001-6911-7221
FU National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
[DK 082843, DK082863, DK082864, DK082866, DK082867, DK082871U01,
DK082872, DK082874, DK082919, DK082923, DK082927, DK082943, U01
DK082944]; NIDDK [A-DK-3002-001]; NIDDK, National Institutes of Health
(NIH); Immunology Center (NIH/NIDDK Center of Molecular Studies in
Digestive and Liver Diseases) [P30DK50306]; Immunology Center (NIH
Public Health Service Research) [M01-RR00040, UL1TR000058]; CTSA
[UL1TR000004, UL1TR001111, UL1RR024986]; Gilead Sciences, Inc.
FX The HBRN was funded by a U01 grant from the National Institute of
Diabetes and Digestive and Kidney Diseases (NIDDK) to the following
investigators: Lewis R. Roberts, M.B., Ch.B., Ph.D. (DK 082843); Anna
Suk-Fong Lok, M.D. (DK082863); Steven H. Belle, Ph.D., MScHyg
(DK082864); Kyong-Mi Chang, M.D. (DK082866); Michael W. Fried, M.D.
(DK082867); Adrian M. Di Bisceglie, M.D. (DK082871); William M. Lee,
M.D. (U01 DK082872); Harry L.A. Janssen, M.D., Ph.D. (DK082874); Daryl
T.-Y. Lau, M.D., M.P.H. (DK082919); Richard K. Sterling, M.D., M.Sc.
(DK082923); Steven-Huy B. Han, M.D. (DK082927); Robert C. Carithers,
M.D. (DK082943); Norah A. Terrault, M.D., M.P.H. (U01 DK082944); an
interagency agreement with NIDDK: Lilia M. Ganova-Raeva, Ph.D.
(A-DK-3002-001) and support from the intramural program, NIDDK, National
Institutes of Health (NIH): Marc G. Ghany, M.D. Additional funding to
support this study was provided to Kyong-Mi Chang, M.D., the Immunology
Center (NIH/NIDDK Center of Molecular Studies in Digestive and Liver
Diseases P30DK50306, NIH Public Health Service Research Grant
M01-RR00040), Richard K. Sterling, M.D., M.Sc. (UL1TR000058, NCATS
[National Center for Advancing Translational Sciences], NIH), Norah A.
Terrault, M.D., M.P.H. (CTSA grant no: UL1TR000004), Michael W. Fried,
M.D. (CTSA grant no.: UL1TR001111), and Anna Suk-Fong Lok (CTSA grant
no.: UL1RR024986). Additional support was provided by Gilead Sciences,
Inc., and Roche Molecular Systems by a CRADA through the NIDDK.
NR 40
TC 8
Z9 8
U1 1
U2 9
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 NOV
PY 2015
VL 62
IS 5
BP 1364
EP 1374
DI 10.1002/hep.28110
PG 11
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA CU1EZ
UT WOS:000363264100008
PM 26390278
ER
PT J
AU Bloom, MS
Whitcomb, BW
Chen, Z
Ye, A
Kannan, K
Louis, GMB
AF Bloom, M. S.
Whitcomb, B. W.
Chen, Z.
Ye, A.
Kannan, K.
Louis, G. M. Buck
TI Associations between urinary phthalate concentrations and semen quality
parameters in a general population
SO HUMAN REPRODUCTION
LA English
DT Article
DE endocrine disrupting chemicals; phthalates; plasticizers; semen; sperm
ID ENDOCRINE-DISRUPTING CHEMICALS; FETAL TESTIS XENOGRAFTS;
SEXUAL-DIFFERENTIATION; OXIDATIVE METABOLITES; REPRODUCTIVE FUNCTION;
MULTIPLE COMPARISONS; SPERM MORPHOLOGY; SERUM COTININE; UNITED-STATES;
MALE-RAT
AB STUDY QUESTION: Are urinary phthalate concentrations associated with altered semen quality parameters among males recruited from the general population?
SUMMARY ANSWER: Urinary levels of metabolites of phthalate diesters are associated with lower total sperm counts, larger sperm head sizes, and higher percentages of morphologically abnormal sperm.
WHAT IS KNOWN ALREADY: High dose experiments in rats implicate phthalates as anti-androgens. Studies involving infertile men seeking care suggest that phthalates influence measures of semen quality raising concern about the implications for men in the general population.
STUDY DESIGN, SIZE, DURATION: This prospective cohort study comprised 501 male partners in couples discontinuing contraception to become pregnant, who were recruited from 16 US counties using population-based sampling frameworks from 2005 to 2009.
PARTICIPANTS/MATERIALS, SETTING, METHODS: Urine and semen samples were obtained at baseline from 473 (94%) men, of whom 378 (80%) men provided a second sample the following month. Urine was analyzed for 14 monoester metabolites of phthalate diesters by high-performance liquid chromatography coupled to tandem mass spectrometry. Semen samples were analyzed for 34 quality parameters categorized as general, motility, morphology, sperm head and sperm chromatin structure.
MAIN RESULTS AND THE ROLE OF CHANCE: Urinary mono-[2-(carboxymethyl) hexyl] phthalate (MCMHP), mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono-benzyl phthalate (MBzP), and mono-isononyl phthalate (MNP) were significantly associated with lower total sperm counts and concentrations, larger sperm head sizes, higher proportions of megalo head sperm morphology, and/or other morphological changes. Urinary mono-methyl phthalate (MMP) and mono-cyclohexyl phthalate (MCPP) were significantly associated with lower sperm motility, and urine mono-2-ethylhexyl phthalate (MEHP) was significantly associated with higher sperm motility.
LIMITATIONS, REASONS FOR CAUTION: While adverse associations were observed, the implications of the findings for couple fecundity and fertility remain to be established. Cautious interpretation is needed in light of reliance on a single measurement of phthalate measure and no correction for multiple comparisons.
C1 [Bloom, M. S.; Kannan, K.] SUNY Albany, Sch Publ Hlth, Dept Environm Hlth Sci, Albany, NY 12144 USA.
[Bloom, M. S.] SUNY Albany, Sch Publ Hlth, Dept Epidemiol & Biostat, Albany, NY 12144 USA.
[Whitcomb, B. W.] Univ Massachusetts, Sch Publ Hlth & Hlth Sci, Div Biostat & Epidemiol, Amherst, MA 01003 USA.
[Chen, Z.; Ye, A.; Louis, G. M. Buck] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Intramural Populat Hlth Res, Rockville, MD 20892 USA.
[Kannan, K.] New York State Dept Hlth, Wadsworth Ctr, Albany, NY 12201 USA.
RP Bloom, MS (reprint author), Sch Publ Hlth, Rm 157,One Univ Pl, Rensselaer, NY 12144 USA.
EM mbloom@albany.edu
OI Bloom, Michael/0000-0002-0028-5494; Buck Louis,
Germaine/0000-0002-1774-4490
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development [N01-HD-3-3355, N01-HD-3-3356, NOH-HD-3-3358]
FX This study was supported by the Intramural Research Program of the
Eunice Kennedy Shriver National Institute of Child Health and Human
Development (N01-HD-3-3355, N01-HD-3-3356 and NOH-HD-3-3358).
NR 70
TC 14
Z9 14
U1 9
U2 17
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 NOV
PY 2015
VL 30
IS 11
BP 2645
EP 2657
DI 10.1093/humrep/dev219
PG 13
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA CT8GQ
UT WOS:000363053400022
PM 26350610
ER
PT J
AU Ojukwu, M
Mbizo, J
Leyva, B
Olaku, O
Zia, F
AF Ojukwu, Mary
Mbizo, Justice
Leyva, Bryan
Olaku, Oluwadamilola
Zia, Farah
TI Complementary and Alternative Medicine Use Among Overweight and Obese
Cancer Survivors in the United States
SO INTEGRATIVE CANCER THERAPIES
LA English
DT Article
DE alternative; cancer; complementary; medicine; obese; overweight;
survivors
ID BREAST-CANCER; RADICAL PROSTATECTOMY; PHYSICAL-ACTIVITY;
CARDIOVASCULAR-DISEASE; NATIONAL-SURVEY; POOR-PROGNOSIS; WEIGHT CONTROL;
CAM USE; THERAPIES; DIAGNOSIS
AB Purpose. The purpose of the study was to determine the prevalence of complementary and alternative medicine (CAM) use among US cancer survivors; examine whether use varies by underweight/normal weight, overweight, and obese body mass index status; determine reasons for use; and document disclosure rates of CAM use to medical professionals. Methods. Data for 1785 cancer survivors were obtained from the 2007 National Health Interview Survey and CAM supplement. The prevalence and associations of CAM use in the previous 12 months were compared among underweight/normal weight, overweight, and obese adult cancer survivors. Results. Nearly 90% of cancer survivors used at least one type of CAM therapy in the 12 months preceding the survey. Those who were overweight, but not obese, were more likely to use a CAM modality compared to normal/underweight respondents. Over two thirds (71%) reported using CAM therapy for general health and wellness and 39.3% used CAM because a health care provider recommended it. Disclosure rates of CAM use to conventional medical professionals varied widely by CAM modality. Conclusions. An overwhelming majority of US cancer survivors use CAM for a variety of reasons. Overweight cancer survivors may be more likely to use CAM than those who are underweight, normal weight, or obese. Cancer survivors should be screened by medical providers for the use of CAM therapies; furthermore, prospective clinical research evaluating the efficacy and safety of biologically based CAM therapies, often used by cancer survivors, is important and necessary for the well-being of this population.
C1 [Ojukwu, Mary; Olaku, Oluwadamilola; Zia, Farah] NCI, Off Canc Complementary & Alternat Med, Bethesda, MD 20892 USA.
[Mbizo, Justice] Univ W Florida, Pensacola, FL 32514 USA.
[Leyva, Bryan] NCI, Proc Care Res Branch, Bethesda, MD 20892 USA.
[Olaku, Oluwadamilola] Kelly Serv Inc, Rockville, MD USA.
RP Olaku, O (reprint author), NCI, Off Canc Complementary & Alternat Med, 9609 Med Ctr Dr, Bethesda, MD 20892 USA.
EM Olakuo@mail.nih.gov
FU National Cancer Institute (NCI)
FX The author(s) disclosed receipt of the following financial support for
the research, authorship, and/or publication of this article: Funding
for this manuscript was provided by the National Cancer Institute (NCI).
The NCI did not participate in the design, analysis, interpretation of
data and writing of manuscript.
NR 71
TC 2
Z9 2
U1 3
U2 8
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 1534-7354
EI 1552-695X
J9 INTEGR CANCER THER
JI Integr. Cancer Ther.
PD NOV
PY 2015
VL 14
IS 6
BP 503
EP 514
DI 10.1177/1534735415589347
PG 12
WC Oncology; Integrative & Complementary Medicine
SC Oncology; Integrative & Complementary Medicine
GA CT8JW
UT WOS:000363063200002
PM 26044767
ER
PT J
AU Poniewierska-Baran, A
Suszynska, M
Sun, WY
Abdelbaset-Ismail, A
Schneider, G
Barr, FG
Ratajczak, MZ
AF Poniewierska-Baran, Agata
Suszynska, Malwina
Sun, Wenyue
Abdelbaset-Ismail, Ahmed
Schneider, Gabriela
Barr, Frederic G.
Ratajczak, Mariusz Z.
TI Human rhabdomyosarcoma cells express functional erythropoietin receptor:
Potential therapeutic implications
SO INTERNATIONAL JOURNAL OF ONCOLOGY
LA English
DT Article
DE rhabdomyosarcoma; erythropoietin; erythropoietin receptor; metastasis
ID TISSUE-LEVELS INCREASE; ALVEOLAR RHABDOMYOSARCOMA; PROMETASTATIC
FACTORS; METASTATIC BEHAVIOR; HUMAN NEUROBLASTOMA; INHIBITORY FACTOR;
BIOACTIVE LIPIDS; GENE-EXPRESSION; CANCER CELLS; GERMLINE
AB The erythropoietin receptor (EpoR) is expressed by cells from the erythroid lineage; however, evidence has accumulated that it is also expressed by some solid tumors. This is an important observation, because recombinant erythropoietin (EPO) is employed in cancer patients to treat anemia related to chemo/radiotherapy. In our studies we employed eight rhabdomyosarcoma (RMS) cell lines (three alveolar-type RMS cell lines and five embrional-type RMS cell lines), and mRNA samples obtained from positive, PAX7-FOXO1-positive, and fusion-negative RMS patient samples. Expression of EpoR was evaluated by RT-PCR, gene array and FACS. The functionality of EpoR in RMS cell lines was evaluated by chemotaxis, adhesion, and direct cell proliferation assays. In some of the experiments, RMS cells were exposed to vincristine (VCR) in the presence or absence of EPO to test whether EPO may impair the therapeutic effect of VCR. We report for a first time that functional EpoR is expressed in human RMS cell lines as well as by primary tumors from RMS patients. Furthermore, EpoR is detectably expressed in both embryonal and alveolar RMS subtypes. At the functional level, several human RMS cell lines responded to EPO stimulation by enhanced proliferation, chemotaxis, cell adhesion, and phosphorylation of MAPKp42/44 and AKT. Moreover, RMS cells became more resistant to VCR treatment in the presence of EPO. Our findings have important potential clinical implications, indicating that EPO supplementation in RMS patients may have the unwanted side effect of tumor progression.
C1 [Poniewierska-Baran, Agata; Suszynska, Malwina; Abdelbaset-Ismail, Ahmed; Schneider, Gabriela; Ratajczak, Mariusz Z.] Univ Louisville, James Graham Brown Canc Ctr, Stem Cell Inst, Louisville, KY 40202 USA.
[Poniewierska-Baran, Agata; Suszynska, Malwina] Pomeranian Med Univ, Dept Physiol, Szczecin, Poland.
[Sun, Wenyue; Ratajczak, Mariusz Z.] Med Univ Warsaw, Dept Regenerat Med, Warsaw, Poland.
[Barr, Frederic G.] NCI, Pathol Lab, Bethesda, MD 20892 USA.
RP Ratajczak, MZ (reprint author), Univ Louisville, James Graham Brown Canc Ctr, Stem Cell Inst, 500 S Floyd St,Room 107, Louisville, KY 40202 USA.
EM mzrata01@louisville.edu
OI Abdelbaset Ismail, Ahmed/0000-0002-2135-1753
FU NIH [2R01 DK074720, R01HL112788]; Stella and Henry Endowment; Maestro
grant [2011/02/A/NZ4/00035]; National Cancer Institute
FX The present study was supported by NIH grants (nos. 2R01 DK074720 and
R01HL112788), the Stella and Henry Endowment, and the Maestro grant
2011/02/A/NZ4/00035 awarded to M.-Z.R. Work by F.-G.B. and W.S. was
supported by the Intramural Research Program of the National Cancer
Institute.
NR 34
TC 2
Z9 2
U1 0
U2 3
PU SPANDIDOS PUBL LTD
PI ATHENS
PA POB 18179, ATHENS, 116 10, GREECE
SN 1019-6439
EI 1791-2423
J9 INT J ONCOL
JI Int. J. Oncol.
PD NOV
PY 2015
VL 47
IS 5
BP 1989
EP 1997
DI 10.3892/ijo.2015.3184
PG 9
WC Oncology
SC Oncology
GA CU2LV
UT WOS:000363355900040
PM 26412593
ER
PT J
AU Gafni, RI
Guthrie, LC
Kelly, MH
Brillante, BA
Christie, CM
Reynolds, JC
Yovetich, NA
James, R
Collins, MT
AF Gafni, Rachel I.
Guthrie, Lori C.
Kelly, Marilyn H.
Brillante, Beth A.
Christie, C. Michele
Reynolds, James C.
Yovetich, Nancy A.
James, Robert
Collins, Michael T.
TI Transient Increased Calcium and Calcitriol Requirements After
Discontinuation of Human Synthetic Parathyroid Hormone 1-34 (hPTH 1-34)
Replacement Therapy in Hypoparathyroidism
SO JOURNAL OF BONE AND MINERAL RESEARCH
LA English
DT Article
DE PARATHYROID-RELATED DISORDERS; PTH; BIOCHEMICAL MARKERS OF BONE
TURNOVER; DXA; HORMONE REPLACEMENT
ID BONE-MINERAL DENSITY; LONG-TERM TREATMENT; PRIMARY HYPERPARATHYROIDISM;
POSTMENOPAUSAL WOMEN; VITAMIN-D; OSTEOPOROSIS; TURNOVER; SKELETON;
DIFFERENTIATION; PTH(1-84)
AB Synthetic human PTH 1-34 (hPTH 1-34) replacement therapy in hypoparathyroidism maintains eucalcemia and converts quiescent bone to high-turnover bone. However, the skeletal and metabolic effects of drug discontinuation have not been reported. Nine subjects with hypoparathyroidism received subcutaneous injections of hPTH 1-34 two to three times daily for 19.8 to 61.3 months and then transitioned back to calcium and calcitriol. Biochemistries and bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA) were assessed at baseline, while on treatment, and at follow-up 3 to 12 months after drug discontinuation. Two subjects developed hypocalcemia when hPTH 1-34 was abruptly discontinued. Thus, to avoid hypocalcemia, subjects were slowly weaned from hPTH 1-34 over several weeks. When hPTH 1-34 was stopped, subjects were requiring two to three times pretreatment doses of calcitriol and calcium to maintain blood calcium levels. Doses were gradually reduced over many weeks until calcium levels were stable on doses similar to baseline. Bone-specific alkaline phosphatase (BSAP), N-telopeptide (NTX), and osteocalcin (OC) increased significantly with hPTH 1-34; at follow-up, BSAP and NTX had returned to baseline while OC was still slightly elevated. During treatment, BMD was unchanged at the hip and lateral spine but declined at the anterior-posterior (AP) spine, radius, and total body. During weaning, BMD increased, with the hip and lateral spine exceeding pre-hPTH 1-34 values and the whole body returning to baseline. AP spine was increased non-significantly compared to baseline at follow-up. hPTH 1-34 must be gradually weaned in hypoparathyroid patients with high doses of oral medications given to avoid hypocalcemia. The transient increased requirements accompanied by increased BMD after long-term hPTH 1-34 therapy suggest a reversal of the expanded remodeling space favoring bone formation as the skeleton returns to a low-turnover state, reminiscent of the hungry bone syndrome. Further study and close monitoring is required to ensure safe transition to conventional therapy and to elucidate the physiological mechanism of this phenomenon. (c) 2015 American Society for Bone and Mineral Research.
C1 [Gafni, Rachel I.; Guthrie, Lori C.; Kelly, Marilyn H.; Brillante, Beth A.; Collins, Michael T.] Natl Inst Dent & Craniofacial Res, Skeletal Clin Studies Unit, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD 20892 USA.
[Christie, C. Michele] Kaiser Permanente, Dept Pediat, Springfield, VA USA.
[Reynolds, James C.] NIH, Ctr Clin, Dept Nucl Med, Bethesda, MD 20892 USA.
[Yovetich, Nancy A.; James, Robert] Rho Inc, Chapel Hill, NC USA.
RP Gafni, RI (reprint author), NIDCR, NIH, Bldg 30,Room 228,30 Convent Dr MSC 4320, Bethesda, MD 20892 USA.
EM gafnir@mail.nih.gov
FU DIR, NIDCR, a part of the Intramural Research Program of the NIH, DHHS
FX This research was supported, in part, by the DIR, NIDCR, a part of the
Intramural Research Program of the NIH, DHHS.
NR 33
TC 4
Z9 4
U1 0
U2 0
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 NOV
PY 2015
VL 30
IS 11
BP 2112
EP 2118
DI 10.1002/jbmr.2555
PG 7
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA CU1MV
UT WOS:000363286900018
PM 25990370
ER
PT J
AU Whitehead, TR
Ward, MH
Colt, JS
Dahl, G
Ducore, J
Reinier, K
Gunier, RB
Hammond, SK
Rappaport, SM
Metayer, C
AF Whitehead, Todd P.
Ward, Mary H.
Colt, Joanne S.
Dahl, Gary
Ducore, Jonathan
Reinier, Kyndaron
Gunier, Robert B.
Hammond, S. Katharine
Rappaport, Stephen M.
Metayer, Catherine
TI Dust metal loadings and the risk of childhood acute lymphoblastic
leukemia
SO JOURNAL OF EXPOSURE SCIENCE AND ENVIRONMENTAL EPIDEMIOLOGY
LA English
DT Article
DE childhood acute lymphoblastic leukemia; dust; environmental exposure;
lead; metals
ID IN-HOUSE DUST; POLYCYCLIC AROMATIC-HYDROCARBONS; POLYBROMINATED DIPHENYL
ETHERS; PARENTAL OCCUPATIONAL-EXPOSURE; RESIDENTIAL DUST; TEMPORAL
VARIABILITY; DRINKING-WATER; LEAD LEVELS; CHILDREN; CANCER
AB We evaluated the relationship between the risk of childhood acute lymphoblastic leukemia (ALL) and the levels of metals in carpet dust A dust sample was collected from the homes of 142 ALL cases and 187 controls participating in the California Childhood Leukemia Study using a high volume small surface sampler (2001-2006). Samples were analyzed using microwave-assisted acid digestion in combination with inductively coupled plasma mass spectrometry for arsenic, cadmium, chromium, copper, lead, nickel, tin, tungsten, and zinc. Eight metals were detected in at least 85% of the case and control homes; tungsten was detected in <15% of homes. Relationships between dust metal loadings (mu g metal per m(2) carpet) and ALL risk were modeled using multivariable logistic regression, adjusting for the child's age, sex, and race/ethnicity and confounders, including household annual income. A doubling of dust metal loadings was not associated with significant changes in ALL risk (odds ratio (95% confidence interval): arsenic: 0.96 (0.86, 1.07), cadmium: 0.92 (0.81, 1.05), chromium: 1.01 (0.90, 1.14), copper: 0.97 (0.91, 1.03), lead: 1.01 (0.93, 1.10), nickel: 0.95 (0.82, 1.09), tin: 0.96 (0.86, 1.08), and zinc: 0.94 (0.84, 1.05)). Our findings do not support the hypothesis that metals in carpet dust are risk factors for childhood ALL.
C1 [Whitehead, Todd P.; Gunier, Robert B.; Hammond, S. Katharine; Rappaport, Stephen M.; Metayer, Catherine] Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94704 USA.
[Ward, Mary H.; Colt, Joanne S.] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, US Dept HHS,NIH, Bethesda, MD 20892 USA.
[Dahl, Gary] Stanford Univ, Dept Pediat, Lucile Salter Packard Childrens Hosp, Palo Alto, CA 94304 USA.
[Ducore, Jonathan] Univ Calif Davis, Sch Med, Dept Pediat, Sacramento, CA 95817 USA.
[Reinier, Kyndaron] Cedars Sinai Med Ctr, Cedars Sinai Heart Inst, Los Angeles, CA 90048 USA.
RP Whitehead, TR (reprint author), Univ Calif Berkeley, Sch Publ Hlth, 1995 Univ Ave,Suite 460, Berkeley, CA 94704 USA.
EM toddpwhitehead@berkeley.edu
FU National Institute of Environmental Health Sciences (NIEHS)
[R01ES009137, P42ES0470518]; Intramural Research Program of the National
Cancer Institute (NCI), National Institute of Health [7590-S-04,
7590-S-01]; NCI [N02-CP-11015]
FX This work was supported in part by the National Institute of
Environmental Health Sciences (NIEHS, grant numbers R01ES009137 and
P42ES0470518); by the Intramural Research Program of the National Cancer
Institute (NCI), National Institute of Health (Subcontracts
7590-S-04,7590-S-01); and by the NCI (Contract N02-CP-11015). We thank
the families for their participation. We also thank the clinical
investigators at the following collaborating hospitals for the help in
recruiting patients: University of California Davis Medical Center (Dr.
Jonathan Ducore), University of California San Francisco (Drs. Mignon
Loh and Katherine Matthay), Children's Hospital of Central California
(Dr. Vonda Crouse), Lucile Packard Children's Hospital (Dr. Gary Dahl),
Children's Hospital Oakland (Dr. James Feusner), Kaiser Permanente
Oakland (Drs. Daniel Kronish and Stacy Month), Kaiser Permanente
Roseville (Drs. Kent Jolly and Vincent Kiley), Kaiser Permanente Santa
Clara (Drs. Carolyn Russo, Denah Taggart, and Alan Wong), and Kaiser
Permanente San Francisco (Dr. Kenneth Leung). We thank Mr. Adam Abbgy of
the Battelle Memorial Institute for his contribution as an analytical
chemist. We acknowledge the late Dr. Patricia Buffler, the founding
principal investigator of the California Childhood Leukemia Study, and
her leadership of the study for nearly 20 years. Finally, we acknowledge
the study staff for their effort and dedication.
NR 56
TC 0
Z9 0
U1 3
U2 4
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1559-0631
EI 1559-064X
J9 J EXPO SCI ENV EPID
JI J. Expo. Sci. Environ. Epidemiol.
PD NOV-DEC
PY 2015
VL 25
IS 6
BP 593
EP 598
DI 10.1038/jes.2015.9
PG 6
WC Environmental Sciences; Public, Environmental & Occupational Health;
Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Toxicology
GA CU0QX
UT WOS:000363224900007
PM 25736162
ER
PT J
AU O'Brien, TR
Pfeiffer, RM
Paquin, A
Kuhs, KAL
Chen, S
Bonkovsky, HL
Edlin, BR
Howell, CD
Kirk, GD
Kuniholm, MH
Morgan, TR
Strickler, HD
Thomas, DL
Prokunina-Olsson, L
AF O'Brien, Thomas R.
Pfeiffer, Ruth M.
Paquin, Ashley
Kuhs, Krystle A. Lang
Chen, Sabrina
Bonkovsky, Herbert L.
Edlin, Brian R.
Howell, Charles D.
Kirk, Gregory D.
Kuniholm, Mark H.
Morgan, Timothy R.
Strickler, Howard D.
Thomas, David L.
Prokunina-Olsson, Ludmila
TI Comparison of functional variants in IFNL4 and IFNL3 for association
with HCV clearance
SO JOURNAL OF HEPATOLOGY
LA English
DT Article
DE Genetics; IL28B; IFNL3; IFNL4; Innate immunity; Interferon lambda;
Treatment; Viral clearance
ID HEPATITIS-C VIRUS; INTERFERON-LAMBDA FAMILY; GENOME-WIDE ASSOCIATION;
INJECTION-DRUG USERS; GENOTYPE 1 INFECTION; PEGYLATED INTERFERON;
GENETIC-VARIATION; RIBAVIRIN TREATMENT; VIRAL CLEARANCE; IL28B
AB Background & Aims: Genetic polymorphisms within the interferon lambda (IFN-lambda) region are strongly associated with hepatitis C virus (HCV) clearance; the IFNL4-Delta G/TT (rs368234815) polymorphism, which controls the generation of IFN-lambda 4 protein, is more strongly associated with HCV clearance than rs12979860 (the 'IL28B variant'). An IFNL3 3' untranslated region polymorphism (rs4803217) has been proposed as a causal variant that may affect HCV clearance by altering IFNL3 mRNA stability.
Methods: We compared IFNL4-Delta G/TT and rs4803217 for association with response to pegylated-IFN-alpha/ribavirin in the VIRAHEP-C and HALT-C trials, and spontaneous HCV clearance in the ALIVE, UHS and WIHS studies. Genotyping was performed with TaqMan assays. We compared differences in mean reduction in HCV RNA levels by genotype and haplotype. For HCV clearance, we calculated p-values comparing c-statistics for IFNL4-Delta G/TT and rs4803217 genotypes by a bootstrap approach.
Results: Among European Americans, linkage disequilibrium between IFNL4-Delta G/TT and rs4803217 was strong (r(2) = 0.89-0.99) and there were no significant differences between the variants. In African American (AA) individuals enrolled in VIRAHEP-C, HCV RNA at treatment day 28 was more strongly associated with IFNL4-Delta G/TT than rs4803217 (p = 0.003); the IFNL4-Delta G:rs48 03217-G haplotype, which includes the putatively favorable IFNL3 allele, was actually associated with the poorest day 28 response (p = 0.03, comparison to IFNL4-Delta G:rs4803217-T haplotype). Among AA participants, associations were stronger for IFNL4-Delta G/TT than rs4803217 for undetectable HCV RNA at week 24 in Virahep-C (p = 0.03) and week 20 in HALT-C (p = 0.03), as well as for spontaneous HCV clearance (p = 0.048).
Conclusion: IFNL4-Delta G/TT is the primary IFN-lambda region polymorphism for impaired HCV clearance. Published by Elsevier B.V. on behalf of the European Association for the Study of the Liver.
C1 [O'Brien, Thomas R.; Pfeiffer, Ruth M.; Kuhs, Krystle A. Lang] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Paquin, Ashley; Prokunina-Olsson, Ludmila] NCI, Lab Translat Genom, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Chen, Sabrina] Informat Management Serv Inc, Calverton, MD USA.
[Bonkovsky, Herbert L.] Carolinas HealthCare Syst, Dept Med, Charlotte, NC USA.
[Bonkovsky, Herbert L.] Carolinas HealthCare Syst, Liver Biliary Pancreat Ctr, Charlotte, NC USA.
[Edlin, Brian R.] Natl Dev & Res Inst, New York, NY USA.
[Edlin, Brian R.] Weill Cornell Med Coll, New York, NY USA.
[Howell, Charles D.] Howard Univ, Coll Med, Dept Med, Washington, DC USA.
[Kirk, Gregory D.; Thomas, David L.] Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA.
[Kuniholm, Mark H.; Strickler, Howard D.] Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA.
[Morgan, Timothy R.] VA Long Beach Healthcare Syst, Long Beach, CA USA.
RP O'Brien, TR (reprint author), NCI, Infect & Immunoepidemiol Branch, Div Canc Epidemiol & Genet, 9609 Med Ctr Dr,6E108,MSC 9767, Bethesda, MD 20892 USA.
EM obrient@mail.nih.gov
FU Intramural Research Program of the US National Institutes of Health
(National Cancer Institute, Division of Cancer Epidemiology and
Genetics) [DA R01 013324]; ALIVE cohort [U01-DA-036297, R01-DA-04334,
R01-DA-12568]; US National Institutes of Health [R15 HL117199, U01 DK
065201, U54 DK 083909, R01-DA09532, R01-DA12109, R01-DA13245,
R01-DA16159]; National Cancer Institute [N02-CP-91027, N01-CO-12400];
Substance Abuse and Mental Health Services Administration grant
[H79-TI12103]; National Institute of Diabetes and Digestive and Kidney
Diseases; National Institute of Allergy and Infectious Diseases
[U01-AI-35004, UO1-AI-31834, UO1-AI-34994, UO1-AI-34989, UO1-AI-34993,
UO1-AI-42590]; Eunice Kennedy Shriver National Institute of Child Health
and Human Development [UO1-HD-32632]; National Cancer Institute;
National Institute on Drug Abuse; National Institute on Deafness and
Other Communication Disorders; National Center for Research Resources
(UCSF-CTSI grant) [UL1 RR024131]
FX This research was supported by the Intramural Research Program of the US
National Institutes of Health (National Cancer Institute, Division of
Cancer Epidemiology and Genetics), as well as the following grants: DA
R01 013324 (D.L.T.); ALIVE cohort (G.D.K), U01-DA-036297, R01-DA-04334
and R01-DA-12568, and US National Institutes of Health grants R15
HL117199, U01 DK 065201, U54 DK 083909 (H.L.B.); R01-DA09532,
R01-DA12109, R01-DA13245, and R01-DA16159 (B.R.E.); National Cancer
Institute contracts N02-CP-91027 and N01-CO-12400 (B.R.E.); Substance
Abuse and Mental Health Services Administration grant H79-TI12103
(B.R.E.). The VIRAHEP-C and HALT-C studies were conducted, respectively,
by the VIRAHEP-C and HALT-C Investigators and supported by the National
Institute of Diabetes and Digestive and Kidney Diseases. The data and
samples from the VIRAHEP-C and HALT-C studies reported here were
supplied by the National Institute of Diabetes and Digestive and Kidney
Diseases Central Repositories. This manuscript was not prepared in
collaboration with the VIRAHEP-C study group or the HALT-C study group
and does not necessarily reflect the opinions or views of the VIRAHEP-C
Trial and HALT-C Trial, the National Institute of Diabetes and Digestive
and Kidney Diseases Central Repositories or the National Institute of
Diabetes and Digestive and Kidney Diseases. Data in this manuscript were
collected by the Women's Interagency HIV Study (WIHS) Collaborative
Study Group with centers (principal investigators) located at: New York
City/Bronx Consortium (Kathryn Anastos); Brooklyn, NY (Howard Minkoff);
Washington DC Metropolitan Consortium (Mary Young); The Connie Wofsy
Study Consortium of Northern California (Ruth Greenblatt); Los Angeles
County/Southern California Consortium (Alexandra Levine); Chicago
Consortium (Mardge Cohen); and Data Analysis Center (Stephen Gange). The
WIHS is funded by the National Institute of Allergy and Infectious
Diseases (U01-AI-35004, UO1-AI-31834, UO1-AI-34994, UO1-AI-34989,
UO1-AI-34993, and UO1-AI-42590) and by the Eunice Kennedy Shriver
National Institute of Child Health and Human Development (UO1-HD-32632).
The WIHS is co-funded by the National Cancer Institute, the National
Institute on Drug Abuse, and the National Institute on Deafness and
Other Communication Disorders. Funding is also provided by the National
Center for Research Resources (UCSF-CTSI grant UL1 RR024131). The
content of this publication does not necessarily reflect the views or
policies of the US Department of Health and Human Services nor does
mention of trade names, commercial products or organizations imply
endorsement by the US government.
NR 43
TC 14
Z9 14
U1 1
U2 5
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0168-8278
EI 1600-0641
J9 J HEPATOL
JI J. Hepatol.
PD NOV
PY 2015
VL 63
IS 5
BP 1103
EP 1110
DI 10.1016/j.jhep.2015.06
PG 8
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA CU1US
UT WOS:000363307600009
PM 26186989
ER
PT J
AU Subleski, JJ
Scarzello, AJ
Alvord, WG
Jiang, Q
Stauffer, JK
Kronfli, A
Saleh, B
Back, T
Weiss, JM
Wiltrout, RH
AF Subleski, Jeff J.
Scarzello, Anthony J.
Alvord, W. Gregory
Jiang, Qun
Stauffer, Jimmy K.
Kronfli, Anthony
Saleh, Bahara
Back, Timothy
Weiss, Jonathan M.
Wiltrout, Robert H.
TI Serum-based tracking of de novo initiated liver cancer progression
reveals early immunoregulation and response to therapy
SO JOURNAL OF HEPATOLOGY
LA English
DT Article
DE Sleeping Beauty Transposition; HCC; HCA; Gaussia Luciferase; Real-time
tracking; Treatment
ID CYTOTOXIC T-LYMPHOCYTES; HEPATOCELLULAR-CARCINOMA; SOMATIC MUTATIONS;
CELLS; ACTIVATION; SYSTEM; TUMORS; PD-1
AB Background & Aims: Liver inflammatory diseases associated with cancer promoting somatic oncogene mutations are increasing in frequency. Preclinical cancer models that allow for the study of early tumor progression are often protracted, which limits the experimental study parameters due to time and expense. Here we report a robust inexpensive approach using Sleeping Beauty transposition (SBT) delivery of oncogenes along with Gaussia Luciferase expression vector GLuc, to assess de novo liver tumor progression, as well as the detection of innate immune responses or responses induced by therapeutic intervention.
Methods: Tracking de novo liver tumor progression with GLuc was demonstrated in models of hepatocellular carcinoma (HCC) or adenoma (HCA) initiated by hydrodynamic delivery of SBT oncogenes.
Results: Rising serum luciferase levels correlated directly with increasing liver tumor burden and eventual morbidity. Early detection of hepatocyte apoptosis from mice with MET+CAT transfected hepatocytes was associated with a transient delay in HCC growth mediated by a CD8(+) T-cell response against transformed hepatocytes. Furthermore, mice that lack B cells or macrophages had an increase in TUNEL+ hepatocytes following liver MET transfection demonstrating that these cells provide protection from MET-induced hepatocyte apoptosis. Treatment with IL-18+IL-12 of mice displaying established HCC decreased tumor burden which was associated with decreased levels of serum luciferase.
Conclusions: Hydrodynamic delivery of the SBT vector GLuc to hepatocytes serves as a simple blood-based approach for real-time tracking of pathologically distinct types of liver cancer. This revealed tumor-induced immunologic responses and was beneficial in monitoring the efficacy of therapeutic interventions. Published by Elsevier B.V. on behalf of the European Association for the Study of the Liver.
C1 [Subleski, Jeff J.; Scarzello, Anthony J.; Jiang, Qun; Stauffer, Jimmy K.; Kronfli, Anthony; Saleh, Bahara; Back, Timothy; Weiss, Jonathan M.; Wiltrout, Robert H.] NCI, Canc & Inflammat Program, Ctr Canc Res, NIH, Frederick, MD 21702 USA.
[Alvord, W. Gregory] Data Management Serv Inc, Stat Consulting, Frederick Natl Lab Canc Res, Frederick, MD USA.
RP Wiltrout, RH (reprint author), NCI, Expt Therapeut Sect, Canc & Inflammat Program, Ctr Canc Res,NIH, Frederick, MD 21702 USA.
EM wiltrour@mail.nih.gov
FU Intramural Research Program of the National Cancer Institute at the
National Institutes of Health (NCI/NIH), United States
FX This work was supported by the Intramural Research Program of the
National Cancer Institute at the National Institutes of Health
(NCI/NIH), United States.
NR 32
TC 3
Z9 3
U1 2
U2 6
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0168-8278
EI 1600-0641
J9 J HEPATOL
JI J. Hepatol.
PD NOV
PY 2015
VL 63
IS 5
BP 1181
EP 1189
DI 10.1016/j.jhep.2015.06.021
PG 9
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA CU1US
UT WOS:000363307600019
PM 26143441
ER
PT J
AU Wigren, M
Nilsson, J
Kaplan, MJ
AF Wigren, M.
Nilsson, J.
Kaplan, M. J.
TI Pathogenic immunity in systemic lupus erythematosus and atherosclerosis:
common mechanisms and possible targets for intervention
SO JOURNAL OF INTERNAL MEDICINE
LA English
DT Review
DE CVD; immune mechanisms; immunotherapy; SLE
ID CORONARY-ARTERY-DISEASE; RECEPTOR-DEFICIENT MICE; REGULATORY T-CELLS;
MIGRATION INHIBITORY FACTOR; TRADITIONAL RISK-FACTORS;
CARDIOVASCULAR-DISEASE; DENSITY-LIPOPROTEIN; I INTERFERON; ACCELERATED
ATHEROSCLEROSIS; MYOCARDIAL-INFARCTION
AB Systemic lupus erythematosus (SLE) is an autoimmune disorder that primarily affects young women and is characterized by inflammation in several organs including kidneys, skin, joints, blood and nervous system. Abnormal immune cellular and humoral responses play important roles in the development of the disease process. Impaired clearance of apoptotic material is a key factor contributing to the activation of self-reactive immune cells. The incidence of atherosclerotic cardiovascular disease (CVD) is increased up to 50-fold in patients with SLE compared to age- and gender-matched controls, and this can only partly be explained by traditional risk factors for CVD. Currently, there is no effective treatment to prevent CVD complications in SLE. Traditional preventive CVD therapies have not been found to significantly lower the incidence of CVD in SLE; therefore, there is a need for novel treatment strategies and increased understanding of the mechanisms involved in the pathogenesis of CVD complications in SLE. The pathogenic immune responses in SLE and development of atherosclerotic plaques share some characteristics, such as impaired efferocytosis and skewed T-cell activation, suggesting the possibility of identifying novel targets for intervention. As novel immune-based therapies for CVD are being developed, it is possible that some of these may be effective for the prevention of CVD and for immunomodulation in SLE. However, further understanding of the mechanisms leading to an increased prevalence of cardiovascular events in SLE is critical for the development of such therapies.
C1 [Wigren, M.; Nilsson, J.] Lund Univ, Dept Clin Sci Malmo, S-20502 Malmo, Sweden.
[Kaplan, M. J.] NIAMSD, System Autoimmun Branch, NIH, Bethesda, MD 20892 USA.
RP Wigren, M (reprint author), Lund Univ, Dept Clin Sci, Jan Waldenstroms Gata 35, S-20502 Malmo, Sweden.
EM maria.wigren@med.lu.se
FU Intramural NIH HHS [ZIA AR041199-01]
NR 104
TC 2
Z9 2
U1 1
U2 9
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0954-6820
EI 1365-2796
J9 J INTERN MED
JI J. Intern. Med.
PD NOV
PY 2015
VL 278
IS 5
BP 494
EP 506
DI 10.1111/joim.12357
PG 13
WC Medicine, General & Internal
SC General & Internal Medicine
GA CU1JX
UT WOS:000363278500006
PM 25720452
ER
PT J
AU Cachia, D
Kamiya-Matsuoka, C
Mandel, JJ
Olar, A
Cykowski, MD
Armstrong, TS
Fuller, GN
Gilbert, MR
De Groot, JF
AF Cachia, David
Kamiya-Matsuoka, Carlos
Mandel, Jacob J.
Olar, Adriana
Cykowski, Matthew D.
Armstrong, Terri S.
Fuller, Gregory N.
Gilbert, Mark R.
De Groot, John F.
TI Primary and secondary gliosarcomas: clinical, molecular and survival
characteristics
SO JOURNAL OF NEURO-ONCOLOGY
LA English
DT Article
DE Gliosarcoma; Primary gliosarcoma; Secondary gliosarcoma; TP53 mutation;
IDH mutation
ID NEWLY-DIAGNOSED GLIOBLASTOMA; CEREBRAL GLIOSARCOMA; BRAIN-TUMORS;
FEATURES; TEMOZOLOMIDE; BEVACIZUMAB; MUTATIONS; IDH1; OSTEOSARCOMA;
METASTASES
AB Gliosarcoma is classified by the World Health Organization as a variant of glioblastoma. These tumors exhibit biphasic histologic and immunophenotypic features, reflecting both glial and mesenchymal differentiation. Gliosarcomas can be further classified into primary (de novo) tumors, and secondary gliosarcomas, which are diagnosed at recurrence after a diagnosis of glioblastoma. Using a retrospective review, patients seen at MD Anderson Cancer Center between 2004 and 2014 with a pathology-confirmed diagnosis of gliosarcoma were identified. 34 patients with a diagnosis of gliosarcoma seen at the time of initial diagnosis or at recurrence were identified (24 primary gliosarcomas (PGS), 10 secondary gliosarcomas (SGS)). Molecular analysis performed on fourteen patients revealed a high incidence of TP53 mutations and, rarely, EGFR and IDH mutations. Median overall survival (OS) for all patients was 17.5 months from the diagnosis of gliosarcoma, with a progression free survival (PFS) of 6.4 months. Comparing PGS with SGS, the median OS was 24.7 and 8.95 months, respectively (from the time of sarcomatous transformation in the case of SGS). The median OS in SGS patients from the initial diagnosis of GB was 25 months, with a PFS of 10.7 months. Molecular analysis revealed a higher than expected rate of TP53 mutations in GS patients and, typical of primary glioblastoma, IDH mutations were uncommon. Though our data shows improved outcomes for both PGS and SGS when compared to the literature, this is most likely a reflection of selection bias of patients treated on clinical trials at a quaternary center.
C1 [Cachia, David] Med Univ S Carolina, Dept Neurosurg, Charleston, SC 29425 USA.
[Kamiya-Matsuoka, Carlos; Armstrong, Terri S.; De Groot, John F.] Univ Texas MD Anderson Canc Ctr, Dept Neurooncol, Houston, TX 77030 USA.
[Mandel, Jacob J.] Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA.
[Olar, Adriana; Fuller, Gregory N.] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA.
[Cykowski, Matthew D.] Houston Methodist Hosp, Dept Pathol & Genom Med, Houston, TX 77030 USA.
[Armstrong, Terri S.] Univ Texas Houston, Dept Family Hlth, Hlth Sci Ctr, Sch Nursing, Houston, TX USA.
[Gilbert, Mark R.] NCI, Neurooncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Cachia, D (reprint author), Med Univ S Carolina, Dept Neurosurg, 96 Jonathan Lucas St, Charleston, SC 29425 USA.
EM cachia@musc.edu
RI Gilbert, Mark/J-7494-2016;
OI Gilbert, Mark/0000-0003-2556-9722; Fuller, Gregory/0000-0001-9447-2647
FU Sheikh Khalifa Al Nahyan Ben Zayed Institute for Personalized Cancer
Therapy; MD Anderson Cancer Center Support grant [P30 CA016672];
National Institutes of Health/National Cancer Institute [5T32CA163185];
Merck; Genentech; Glaxo Smith Kline; Sanofi-Aventis; AstraZeneca;
EMD-Serono; Eli Lilly; Novartis; Deciphera Pharmaceuticals
FX We thank Dr Funda Meric-Bernstam MD and Dr Kenna R Shaw PhD for their
invaluable support in preparation of this manuscript. This work was
supported in part by the Sheikh Khalifa Al Nahyan Ben Zayed Institute
for Personalized Cancer Therapy, and the MD Anderson Cancer Center
Support grant (P30 CA016672). A Olar was supported by the National
Institutes of Health/National Cancer Institute (Training Grant No.
5T32CA163185). T.S. Armstrong serves as consultant for Immuno-cellular
therapeutics; is on the advisory board for Roche; receives research
support from Merck and Genentech. M.R. Gilbert reports research support
from Genentech, Merck, Glaxo Smith Kline; receives honoraria from Merck,
Genentech, AbbVie; and serves on the advisory board for Genetech,
AbbVie, Heron Therapeutics. JF de Groot serves as a consultant for
Celldex and Deciphera Pharmaceuticals; serves on the advisory board for
Genentech, Novartis, Celldex, is on the Data and Safety Monitoring Board
for VBL Therapeutics and receives research support from Sanofi-Aventis,
AstraZeneca, EMD-Serono, Eli Lilly, Novartis, Deciphera Pharmaceuticals.
NR 50
TC 2
Z9 2
U1 1
U2 6
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0167-594X
EI 1573-7373
J9 J NEURO-ONCOL
JI J. Neuro-Oncol.
PD NOV
PY 2015
VL 125
IS 2
BP 401
EP 410
DI 10.1007/s11060-015-1930-y
PG 10
WC Oncology; Clinical Neurology
SC Oncology; Neurosciences & Neurology
GA CU0YN
UT WOS:000363245300020
PM 26354773
ER
PT J
AU Pujol, S
Wells, W
Pierpaoli, C
Brun, C
Gee, J
Cheng, G
Vemuri, B
Commowick, O
Prima, S
Stamm, A
Goubran, M
Khan, A
Peters, T
Neher, P
Maier-Hein, KH
Shi, Y
Tristan-Vega, A
Veni, G
Whitaker, R
Styner, M
Westin, CF
Gouttard, S
Norton, I
Chauvin, L
Mamata, H
Gerig, G
Nabavi, A
Golby, A
Kikinis, R
AF Pujol, Sonia
Wells, William
Pierpaoli, Carlo
Brun, Caroline
Gee, James
Cheng, Guang
Vemuri, Baba
Commowick, Olivier
Prima, Sylvain
Stamm, Aymeric
Goubran, Maged
Khan, Ali
Peters, Terry
Neher, Peter
Maier-Hein, Klaus H.
Shi, Yundi
Tristan-Vega, Antonio
Veni, Gopalkrishna
Whitaker, Ross
Styner, Martin
Westin, Carl-Fredrik
Gouttard, Sylvain
Norton, Isaiah
Chauvin, Laurent
Mamata, Hatsuho
Gerig, Guido
Nabavi, Arya
Golby, Alexandra
Kikinis, Ron
TI The DTI Challenge: Toward Standardized Evaluation of Diffusion Tensor
Imaging Tractography for Neurosurgery
SO JOURNAL OF NEUROIMAGING
LA English
DT Article
DE Diffusion MRI; diffusion tensor imaging (DTI); tractography; brain
gliomas; neurosurgery
ID BRAIN-TUMOR SURGERY; VISUALIZATION; TRACT; MRI
AB BACKGROUND AND PURPOSEDiffusion tensor imaging (DTI) tractography reconstruction of white matter pathways can help guide brain tumor resection. However, DTI tracts are complex mathematical objects and the validity of tractography-derived information in clinical settings has yet to be fully established. To address this issue, we initiated the DTI Challenge, an international working group of clinicians and scientists whose goal was to provide standardized evaluation of tractography methods for neurosurgery. The purpose of this empirical study was to evaluate different tractography techniques in the first DTI Challenge workshop.
METHODSEight international teams from leading institutions reconstructed the pyramidal tract in four neurosurgical cases presenting with a glioma near the motor cortex. Tractography methods included deterministic, probabilistic, filtered, and global approaches. Standardized evaluation of the tracts consisted in the qualitative review of the pyramidal pathways by a panel of neurosurgeons and DTI experts and the quantitative evaluation of the degree of agreement among methods.
RESULTSThe evaluation of tractography reconstructions showed a great interalgorithm variability. Although most methods found projections of the pyramidal tract from the medial portion of the motor strip, only a few algorithms could trace the lateral projections from the hand, face, and tongue area. In addition, the structure of disagreement among methods was similar across hemispheres despite the anatomical distortions caused by pathological tissues.
CONCLUSIONSThe DTI Challenge provides a benchmark for the standardized evaluation of tractography methods on neurosurgical data. This study suggests that there are still limitations to the clinical use of tractography for neurosurgical decision making.
C1 [Pujol, Sonia; Wells, William; Mamata, Hatsuho; Kikinis, Ron] Harvard Univ, Sch Med, Dept Radiol, Surg Planning Lab,Brigham & Womens Hosp, Boston, MA 02115 USA.
[Pierpaoli, Carlo] NICHHD, Program Pediat Imaging & Tissue Sci, NIH, Bethesda, MD 20892 USA.
[Brun, Caroline; Gee, James] Univ Penn, Penn Image Comp & Sci Lab, Dept Radiol, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Cheng, Guang; Vemuri, Baba] Univ Florida, Dept Comp & Informat Sci & Engn, Gainesville, FL USA.
[Commowick, Olivier; Prima, Sylvain; Stamm, Aymeric] Univ Rennes 1, VISAGES INSERM U746 CNRS UMR6074 INRIA, Rennes, France.
[Goubran, Maged; Khan, Ali; Peters, Terry] Western Univ, Robarts Res Inst, Imaging Labs, London, ON, Canada.
[Neher, Peter; Maier-Hein, Klaus H.] Jr Grp Med Image Comp, Div Med & Biol Informat, German Canc Res Ctr, Heidelberg, Germany.
[Shi, Yundi; Styner, Martin] Univ N Carolina, Dept Psychiat & Comp Sci, Chapel Hill, NC USA.
[Tristan-Vega, Antonio] Univ Valladolid, Dept Mech Engn, Valladolid, Spain.
[Veni, Gopalkrishna; Whitaker, Ross; Gouttard, Sylvain; Gerig, Guido] Univ Utah, Sci Comp & Imaging Inst, Salt Lake City, UT USA.
[Westin, Carl-Fredrik] Harvard Univ, Brigham & Womens Hosp, Lab Math Imaging, Sch Med, Boston, MA 02115 USA.
[Norton, Isaiah; Golby, Alexandra] Harvard Univ, Brigham & Womens Hosp, Dept Neurosurg, Sch Med, Boston, MA 02115 USA.
[Chauvin, Laurent] Harvard Univ, Brigham & Womens Hosp, Surg Nav & Robot Lab, Dept Radiol,Med Sch, Boston, MA 02115 USA.
[Nabavi, Arya] INI, Hannover, Germany.
RP Pujol, S (reprint author), Brigham & Womens Hosp, Surg Planning Lab, Radiol ASBI L1 050, 75 Francis St, Boston, MA 02115 USA.
EM spujol@bwh.harvard.edu
RI Tristan-Vega, Antonio/D-5609-2016; Maier-Hein, Klaus/M-6250-2016; Khan,
Ali/P-1353-2014;
OI Tristan-Vega, Antonio/0000-0002-4614-2501; Maier-Hein,
Klaus/0000-0002-6626-2463; Khan, Ali/0000-0002-0760-8647; Gerig,
Guido/0000-0002-9547-6233
FU National Alliance for Medical Image Computing (NIH) [U54EB005149];
Neuroimage Analysis Center (NIH) [P41RR013218]; National Center for
Image-Guided Therapy (NIH) [NCIGT P41EB015898]
FX This work was partially funded by the National Alliance for Medical
Image Computing (NIH Grant U54EB005149), the Neuroimage Analysis Center
(NIH Grant P41RR013218), and the National Center for Image-Guided
Therapy (NIH Grant NCIGT P41EB015898).
NR 20
TC 9
Z9 9
U1 2
U2 14
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1051-2284
EI 1552-6569
J9 J NEUROIMAGING
JI J. Neuroimaging
PD NOV-DEC
PY 2015
VL 25
IS 6
BP 875
EP 882
DI 10.1111/jon.12283
PG 8
WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA CU2DW
UT WOS:000363334100004
PM 26259925
ER
PT J
AU Gomez-Castillo, BJ
Hirsch, R
Groninger, H
Baker, K
Cheng, MJ
Phillips, J
Pollack, J
Berger, AM
AF Gomez-Castillo, Blanca J.
Hirsch, Rosemarie
Groninger, Hunter
Baker, Karen
Cheng, M. Jennifer
Phillips, Jayne
Pollack, John
Berger, Ann M.
TI Increasing the Number of Outpatients Receiving Spiritual Assessment: A
Pain and Palliative Care Service Quality Improvement Project
SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT
LA English
DT Article
DE Spirituality; spiritual assessment; quality improvement; palliative care
AB Background. Spirituality is a patient need that requires special attention from the Pain and Palliative Care Service team. This quality improvement project aimed to provide spiritual assessment for all new outpatients with serious life-altering illnesses.
Measures. Percentage of new outpatients receiving spiritual assessment (Faith, Importance/Influence, Community, Address/Action in care, psychosocial evaluation, chaplain consults) at baseline and postinterventions.
Intervention. Interventions included encouraging clinicians to incorporate adequate spiritual assessment into patient care and implementing chaplain covisits for all initial outpatient visits.
Outcomes. The quality improvement interventions increased spiritual assessment (baseline vs. postinterventions): chaplain covisits (25.5% vs. 50%), Faith, Importance/Influence, Community, Address/Action in care completion (49% vs. 72%), and psychosocial evaluation (89% vs. 94%).
Conclusions/Lessons Learned. Improved spiritual assessment in an outpatient palliative care clinic setting can occur with a multidisciplinary approach. This project also identifies data collection and documentation processes that can be targeted for improvement. Published by Elsevier Inc. on behalf of American Academy of Hospice and Palliative Medicine.
C1 [Gomez-Castillo, Blanca J.] Georgetown Univ, Med Ctr, Washington, DC 20007 USA.
[Gomez-Castillo, Blanca J.; Hirsch, Rosemarie; Groninger, Hunter; Baker, Karen; Cheng, M. Jennifer; Phillips, Jayne; Pollack, John; Berger, Ann M.] NIH, Pain & Palliat Care Serv, Ctr Clin, Bethesda, MD 20892 USA.
RP Berger, AM (reprint author), NIH, Pain & Palliat Care Serv, Ctr Clin, 10 Ctr Dr,Bldg 10,Room 2-1733, Bethesda, MD 20892 USA.
EM aberger@cc.nih.gov
FU Intramural NIH HHS [Z99 CL999999]
NR 9
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 0885-3924
EI 1873-6513
J9 J PAIN SYMPTOM MANAG
JI J. Pain Symptom Manage.
PD NOV
PY 2015
VL 50
IS 5
BP 724
EP 729
DI 10.1016/j.jpainsymman.2015.05.012
PG 6
WC Health Care Sciences & Services; Medicine, General & Internal; Clinical
Neurology
SC Health Care Sciences & Services; General & Internal Medicine;
Neurosciences & Neurology
GA CU3NX
UT WOS:000363433200018
PM 26166183
ER
PT J
AU Nathan, N
Wang, JA
Li, SW
Cowen, EW
Haughey, M
Moss, J
Darling, TN
AF Nathan, Neera
Wang, Ji-an
Li, Shaowei
Cowen, Edward W.
Haughey, Mary
Moss, Joel
Darling, Thomas N.
TI Improvement of tuberous sclerosis complex (TSC) skin tumors during
long-term treatment with oral sirolimus
SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY
LA English
DT Article
DE angiofibromas; lymphangioleiomyomatosis; mechanistic target of rapamycin
inhibitor; shagreen patch; sirolimus; tuberous sclerosis complex; ungual
fibroma
ID GIANT-CELL ASTROCYTOMA; SPORADIC LYMPHANGIOLEIOMYOMATOSIS; PHASE-3
TRIAL; EVEROLIMUS; ANGIOMYOLIPOMA; EFFICACY; EXIST-1; SAFETY;
ANGIOFIBROMAS; MULTICENTER
AB Background: Oral mechanistic target of rapamycin inhibitors have been shown to reduce visceral tumor volume in patients with tuberous sclerosis complex (TSC).
Objective: We sought to evaluate the cutaneous response to oral sirolimus in patients with TSC and an indication for systemic treatment, including long-term effects.
Methods: A retrospective analysis of 14 adult patients with TSC prescribed sirolimus to treat lymphangioleiomyomatosis was performed. Serial photographs of angiofibromas, shagreen patches, and ungual fibromas taken before, during, and after the treatment period were blinded, then assessed using the Physician Global Assessment of Clinical Condition (PGA). Microscopic and molecular studies were performed on skin tumors harvested before and during treatment.
Results: Sirolimus significantly improved angiofibromas (median treatment duration 12 months; median PGA score 4.5 [range 1.5-5]; Wilcoxon signed rank test, P = .018) and shagreen patches (median treatment duration 10 months; median PGA score 4.5 [range 3.5-5]; Wilcoxon signed rank test, P = .039), whereas ungual fibromas improved in some patients (median treatment duration 6.5 months; median PGA score 4.66 [range 2.75-5]; Wilcoxon signed rank test, P = .109). Clinical, immunohistochemical, or molecular evidence of resistance was not observed (range 5-64 months of treatment).
Limitations: This was a retrospective analysis limited to adult women with lymphangioleiomyomatosis.
Conclusion: Oral sirolimus is an effective long-term therapy for TSC skin tumors, particularly angiofibromas, in patients for whom systemic treatment is indicated.
C1 [Nathan, Neera; Wang, Ji-an; Li, Shaowei; Darling, Thomas N.] Uniformed Serv Univ Hlth Sci, Dept Dermatol, Bethesda, MD 20814 USA.
[Nathan, Neera; Haughey, Mary; Moss, Joel] NHLBI, Cardiovasc & Pulm Branch, NIH, Bethesda, MD 20892 USA.
[Cowen, Edward W.] NIH, Dermatol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Darling, TN (reprint author), Uniformed Serv Univ Hlth Sci, Dept Dermatol, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA.
EM thomas.darling@usuhs.edu
OI Darling, Thomas/0000-0002-5161-1974
FU Intramural NIH HHS [Z01 HL002541-12]; NIAMS NIH HHS [R01 AR062080,
R01AR062080]
NR 26
TC 7
Z9 8
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0190-9622
J9 J AM ACAD DERMATOL
JI J. Am. Acad. Dermatol.
PD NOV
PY 2015
VL 73
IS 5
BP 802
EP 808
DI 10.1016/j.jaad.2015.07.018
PG 7
WC Dermatology
SC Dermatology
GA CU1HL
UT WOS:000363271400022
PM 26365597
ER
PT J
AU Mahar, AL
Compton, C
McShane, LM
Halabi, S
Asamura, H
Rami-Porta, R
Groome, PA
AF Mahar, Alyson L.
Compton, Carolyn
McShane, Lisa M.
Halabi, Susan
Asamura, Hisao
Rami-Porta, Ramon
Groome, Patti A.
CA Amer Joint Comm Canc
TI Refining Prognosis in Lung Cancer A Report on the Quality and Relevance
of Clinical Prognostic Tools
SO JOURNAL OF THORACIC ONCOLOGY
LA English
DT Article
DE Lung cancer; Prognosis; Clinical prediction tools; Prediction models;
Prognostic model
ID MULTIVARIABLE PREDICTION MODEL; TNM CLASSIFICATION; STAGING PROJECT;
EXTERNAL VALIDATION; LABORATORY PARAMETERS; INDIVIDUAL PROGNOSIS;
SALVAGE TREATMENT; MALIGNANT-TUMORS; DIAGNOSIS TRIPOD; 7TH EDITION
AB Introduction: Accurate, individualized prognostication for lung cancer patients requires the integration of standard patient and pathologic factors, biological, genetic, and other molecular characteristics of the tumor. Clinical prognostic tools aim to aggregate information on an individual patient to predict disease outcomes such as overall survival, but little is known about their clinical utility and accuracy in lung cancer.
Methods: A systematic search of the scientific literature for clinical prognostic tools in lung cancer published from January 1, 1996 to January 27, 2015 was performed. In addition, web-based resources were searched. A priori criteria determined by the Molecular Modellers Working Group of the American Joint Committee on Cancer were used to investigate the quality and usefulness of tools. Criteria included clinical presentation, model development approaches, validation strategies, and performance metrics.
Results: Thirty-two prognostic tools were identified. Patients with metastases were the most frequently considered population in non-small-cell lung cancer. All tools for small-cell lung cancer covered that entire patient population. Included prognostic factors varied considerably across tools. Internal validity was not formally evaluated for most tools and only 11 were evaluated for external validity. Two key considerations were highlighted for tool development: identification of an explicit purpose related to a relevant clinical population and clear decision points and prioritized inclusion of established prognostic factors over emerging factors.
Conclusions: Prognostic tools will contribute more meaningfully to the practice of personalized medicine if better study design and analysis approaches are used in their development and validation.
C1 [Mahar, Alyson L.; Groome, Patti A.] Queens Univ, Div Canc Care & Epidemiol, Canc Res Inst, Kingston, ON K7L 3N6, Canada.
[Compton, Carolyn] Arizona State Univ, Phoenix, AZ USA.
[Compton, Carolyn] Mayo Clin, Sch Med, Lab Med & Pathol, Rochester, MN USA.
[McShane, Lisa M.] NCI, Biometr Res Branch, Div Canc Treatment & Diag, Bethesda, MD 20892 USA.
[Halabi, Susan] Duke Univ, Dept Biostat & Bioinformat, Durham, NC USA.
[Halabi, Susan] Alliance Stat & Data Ctr, Durham, NC USA.
[Asamura, Hisao] Natl Canc Ctr, Div Thorac Surg, Tokyo, Japan.
[Rami-Porta, Ramon] Hosp Univ Mutua Terrassa, Dept Thorac Surg, Barcelona, Spain.
RP Groome, PA (reprint author), Queens Canc Res Inst, Canc Res Inst, Div Canc Care & Epidemiol, Level 2,10 Stuart St, Kingston, ON K7L 3N6, Canada.
EM groomep@queensu.ca
FU Intramural NIH HHS [Z99 CA999999]
NR 71
TC 6
Z9 6
U1 1
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1556-0864
EI 1556-1380
J9 J THORAC ONCOL
JI J. Thorac. Oncol.
PD NOV
PY 2015
VL 10
IS 11
BP 1576
EP 1589
DI 10.1097/JTO.0000000000000652
PG 14
WC Oncology; Respiratory System
SC Oncology; Respiratory System
GA CU1WL
UT WOS:000363312700010
PM 26313682
ER
PT J
AU Sardo, L
Hatch, SC
Chen, JB
Nikolaitchik, O
Burdick, RC
De Chen
Westlake, CJ
Lockett, S
Pathak, VK
Hu, WS
AF Sardo, Luca
Hatch, Steven C.
Chen, Jianbo
Nikolaitchik, Olga
Burdick, Ryan C.
De Chen
Westlake, Christopher J.
Lockett, Stephen
Pathak, Vinay K.
Hu, Wei-Shau
TI Dynamics of HIV-1 RNA Near the Plasma Membrane during Virus Assembly
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID ESCRT PROTEIN RECRUITMENT; VIRAL PARTICLES; GAG; ENCAPSIDATION; GENOMES;
VIRION; IDENTIFICATION; VISUALIZATION; SPECIFICITY; SITE
AB To increase our understanding of the events that lead to HIV-1 genome packaging, we examined the dynamics of viral RNA and Gag-RNA interactions near the plasma membrane by using total internal reflection fluorescence microscopy. We labeled HIV-1 RNA with a photoconvertible Eos protein via an RNA-binding protein that recognizes stem-loop sequences engineered into the viral genome. Near-UV light exposure causes an irreversible structural change in Eos and alters its emitted fluorescence from green to red. We studied the dynamics of HIV-1 RNA by photoconverting Eos near the plasma membrane, and we monitored the population of photoconverted red-Eos-labeled RNA signals over time. We found that in the absence of Gag, most of the HIV-1 RNAs stayed near the plasma membrane transiently, for a few minutes. The presence of Gag significantly increased the time that RNAs stayed near the plasma membrane: most of the RNAs were still detected after 30 min. We then quantified the proportion of HIV-1 RNAs near the plasma membrane that were packaged into assembling viral complexes. By tagging Gag with blue fluorescent protein, we observed that only a portion, similar to 13 to 34%, of the HIV-1 RNAs that reached the membrane were recruited into assembling particles in an hour, and the frequency of HIV-1 RNA packaging varied with the Gag expression level. Our studies reveal the HIV-1 RNA dynamics on the plasma membrane and the efficiency of RNA recruitment and provide insights into the events leading to the generation of infectious HIV-1 virions.
IMPORTANCE
Nascent HIV-1 particles assemble on plasma membranes. During the assembly process, HIV-1 RNA genomes must be encapsidated into viral complexes to generate infectious particles. To gain insights into the RNA packaging and virus assembly mechanisms, we labeled and monitored the HIV-1 RNA signals near the plasma membrane. Our results showed that most of the HIV-1 RNAs stayed near the plasma membrane for only a few minutes in the absence of Gag, whereas most HIV-1 RNAs stayed at the plasma membrane for 15 to 60 min in the presence of Gag. Our results also demonstrated that only a small proportion of the HIV-1 RNAs, approximately 1/10 to 1/3 of the RNAs that reached the plasma membrane, was incorporated into viral protein complexes. These studies determined the dynamics of HIV-1 RNA on the plasma membrane and obtained temporal information on RNA-Gag interactions that lead to RNA encapsidation.
C1 [Sardo, Luca; Hatch, Steven C.; Chen, Jianbo; Nikolaitchik, Olga; Hu, Wei-Shau] NCI, Viral Recombinat Sect, Frederick, MD 21701 USA.
[Burdick, Ryan C.] NCI, Viral Mutat Sect, Frederick, MD 21701 USA.
[Westlake, Christopher J.] NCI, HIV Dynam & Replicat Program, Frederick, MD 21701 USA.
[Westlake, Christopher J.] NCI, Membrane Trafficking & Signaling Sect, Lab Cell & Dev Signaling, Frederick, MD 21701 USA.
[De Chen; Lockett, Stephen] Leidos Biomed Res Inc, Frederick Natl Lab Canc Res, Opt Microscopy & Image Anal Lab, Frederick, MD USA.
RP Hu, WS (reprint author), NCI, Viral Recombinat Sect, Frederick, MD 21701 USA.
EM Wei-Shau.Hu@nih.gov
FU Intramural Research Program of the NIH; NCI; CCR; Intramural AIDS
Targeted Antiviral Program; National Cancer Institute, National
Institutes of Health [HHSN261200800001E]
FX This research was supported by the Intramural Research Program of the
NIH, NCI, CCR, by Intramural AIDS Targeted Antiviral Program grant
funding to W.-S.H. and V.K.P., and, in part, by federal funds from the
National Cancer Institute, National Institutes of Health (contract
HHSN261200800001E).
NR 34
TC 9
Z9 9
U1 2
U2 14
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 NOV
PY 2015
VL 89
IS 21
BP 10832
EP 10840
DI 10.1128/JVI.01146-15
PG 9
WC Virology
SC Virology
GA CU3ZP
UT WOS:000363465900009
PM 26292321
ER
PT J
AU Gjessing, MC
Yutin, N
Tengs, T
Senkevich, T
Koonin, E
Ronning, HP
Alarcon, M
Ylving, S
Lie, KI
Saure, B
Tran, L
Moss, B
Dale, OB
AF Gjessing, Mona C.
Yutin, Natalya
Tengs, Torstein
Senkevich, Tania
Koonin, Eugene
Ronning, Hans Petter
Alarcon, Marta
Ylving, Sonja
Lie, Kai-Inge
Saure, Britt
Tran, Linh
Moss, Bernard
Dale, Ole Bendik
TI Erratum for Gjessing et al., Salmon Gill Poxvirus, the Deepest
Representative of the Chordopoxvirinae (vol 89, pg 9348, 2015)
SO JOURNAL OF VIROLOGY
LA English
DT Correction
C1 [Gjessing, Mona C.; Tengs, Torstein; Alarcon, Marta; Ylving, Sonja; Lie, Kai-Inge; Saure, Britt; Tran, Linh; Dale, Ole Bendik] Norwegian Vet Inst, Oslo, Norway.
[Yutin, Natalya; Koonin, Eugene] NIH, Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20892 USA.
[Senkevich, Tania; Moss, Bernard] NIH, NIAID, Viral Dis Lab, Bethesda, MD 20892 USA.
[Ronning, Hans Petter] Sisomar AS, Trollbukta, Straumen, Norway.
RP Gjessing, MC (reprint author), Norwegian Vet Inst, Oslo, Norway.
NR 1
TC 0
Z9 0
U1 1
U2 4
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
EI 1098-5514
J9 J VIROL
JI J. Virol.
PD NOV
PY 2015
VL 89
IS 21
BP 11174
EP 11174
DI 10.1128/JVI.02125-15
PG 1
WC Virology
SC Virology
GA CU3ZP
UT WOS:000363465900041
PM 26432522
ER
PT J
AU Huang, SW
Tai, CH
Fonville, JM
Lin, CH
Wang, SM
Liu, CC
Su, IJ
Smith, DJ
Wang, JR
AF Huang, Sheng-Wen
Tai, Ching-Hui
Fonville, Judith M.
Lin, Chin-Hui
Wang, Shih-Min
Liu, Ching-Chung
Su, Ih-Jen
Smith, Derek J.
Wang, Jen-Ren
TI Mapping Enterovirus A71 Antigenic Determinants from Viral Evolution
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID A H3N2 VIRUSES; SYNTHETIC PEPTIDES; GENETIC EVOLUTION; INFLUENZA-VIRUS;
CAPSID PROTEIN; STRAINS; IDENTIFICATION; ANTIBODIES; RECEPTOR; BINDING
AB Human enterovirus A71 (EV-A71) belongs to the Enterovirus A species in the Picornaviridae family. Several vaccines against EV-A71, a disease causing severe neurological complications or even death, are currently under development and being tested in clinical trials, and preventative vaccination programs are expected to start soon. To characterize the potential for antigenic change of EV-A71, we compared the sequences of two antigenically diverse genotype B4 and B5 strains of EV-A71 and identified substitutions at residues 98, 145, and 164 in the VP1 capsid protein as antigenic determinants. To examine the effects of these three substitutions on antigenicity, we constructed a series of recombinant viruses containing different mutation combinations at these three residues with a reverse genetics system and then investigated the molecular basis of antigenic changes with antigenic cartography. We found that a novel EV-A71 mutant, containing lysine, glutamine, and glutamic acid at the respective residues 98, 145, and 164 in the VP1 capsid protein, exhibited neutralization reduction against patients' antisera and substantially increased virus binding ability to human cells. These observations indicated that this low-neutralization-reactive EV-A71 VP1-98K/145Q/164E mutant potentially increases viral binding ability and that surveillance studies should look out for these mutants, which could compromise vaccine efficacy.
IMPORTANCE
Emerging and reemerging EV-A71 viruses can cause severe neurological etiology, primarily affecting children, especially around Asia-Pacific countries. We identified a set of mutations in EV-A71 that both reduced neutralization activity against humoral immunity in antisera of patients and healthy adults and greatly increased the viral binding ability to cells. These findings provide important insights for EV-A71 antigenic determinants and emphasize the importance of continuous surveillance, especially after EV-A71 vaccination programs begin.
C1 [Huang, Sheng-Wen; Wang, Shih-Min; Liu, Ching-Chung; Wang, Jen-Ren] Natl Cheng Kung Univ, Ctr Infect Dis & Signaling Res, Tainan 70101, Taiwan.
[Lin, Chin-Hui; Wang, Jen-Ren] Natl Cheng Kung Univ, Dept Med Lab Sci & Biotechnol, Tainan 70101, Taiwan.
[Wang, Shih-Min] Natl Cheng Kung Univ, Dept Emergency Med, Tainan 70101, Taiwan.
[Liu, Ching-Chung] Natl Cheng Kung Univ, Dept Pediat, Tainan 70101, Taiwan.
[Wang, Jen-Ren] Natl Hlth Res Inst, Natl Inst Infect Dis & Vaccinol, Tainan, Taiwan.
[Smith, Derek J.] Univ Cambridge, Cambridge, England.
[Smith, Derek J.] Erasmus MC, Rotterdam, Netherlands.
[Fonville, Judith M.] WHO, Collaborating Ctr Modeling Evolut & Control Emerg, Cambridge, England.
[Smith, Derek J.] NIH, Bethesda, MD 20892 USA.
RP Smith, DJ (reprint author), Natl Cheng Kung Univ, Ctr Infect Dis & Signaling Res, Tainan 70101, Taiwan.
EM dsmith@zoo.cam.ac.uk; jrwang@mail.ncku.edu.tw
RI Wang, Ren-Jen/F-5254-2011;
OI Wang, Jen-Ren/0000-0002-4127-4046
FU Center of Infectious Disease and Signaling Research, National Cheng Kung
University, Aim for the Top University Project, Ministry of Education;
Centers for Disease Control, Ministry of Health and Welfare; National
Health Research Institute grant; Ministry of Science and Technology,
Taiwan [101-2321-B-006-027-MY2, 103-2321-B-006-011, 104-2321-B-006-002];
Medical Research Council UK [MR/K021885/1]; Homerton College, Cambridge,
United Kingdom
FX This work was financially supported by the Center of Infectious Disease
and Signaling Research, National Cheng Kung University, Aim for the Top
University Project, Ministry of Education; by a Centers for Disease
Control, Ministry of Health and Welfare, grant; by a National Health
Research Institute grant; and by Ministry of Science and Technology,
Taiwan, grants 101-2321-B-006-027-MY2, 103-2321-B-006-011, and
104-2321-B-006-002. J.M.F. is supported by a Fellowship in Biomedical
Informatics from the Medical Research Council UK (MR/K021885/1) and a
Junior Research Fellowship from Homerton College, Cambridge, United
Kingdom.
NR 34
TC 4
Z9 4
U1 0
U2 1
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
EI 1098-5514
J9 J VIROL
JI J. Virol.
PD NOV
PY 2015
VL 89
IS 22
BP 11500
EP 11506
DI 10.1128/JVI.02035-15
PG 7
WC Virology
SC Virology
GA CU4AC
UT WOS:000363467200027
PM 26339057
ER
PT J
AU Zaritsky, LA
Bedsaul, JR
Zoon, KC
AF Zaritsky, Luna A.
Bedsaul, Jacquelyn R.
Zoon, Kathryn C.
TI Virus Multiplicity of Infection Affects Type I Interferon Subtype
Induction Profiles and Interferon-Stimulated Genes
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID POSITIVE FEEDBACK; EXPRESSION; ALPHA; CELLS; ACTIVATION; RESPONSES;
IRF-7; AMPLIFICATION; TRANSCRIPTION; RECOGNITION
AB Type I interferons (IFNs) are induced upon viral infection and important mediators of innate immunity. While there is 1 beta interferon (IFN-beta) protein, there are 12 different IFN-alpha subtypes. It has been reported extensively that different viruses induce distinct patterns of IFN subtypes, but it has not been previously shown how the viral multiplicity of infection (MOI) can affect IFN induction. In this study, we discovered the novel finding that human U937 cells infected with 2 different concentrations of Sendai virus (SeV) induce 2 distinct type I IFN subtype profiles. Cells infected at the lower MOI induced more subtypes than cells infected at the higher MOI. We found that this was due to the extent of signaling through the IFN receptor (IFNAR). The cells infected at the lower viral MOI induced the IFNAR2-dependent IFN-alpha subtypes 4, 6, 7, 10, and 17, which were not induced in cells infected at higher virus concentrations. IFN-beta and IFN-alpha 1, -2, and -8 were induced in an IFNAR-independent manner in cells infected at both virus concentrations. IFN-alpha 5, -14, -16, and -21 were induced in an IFNAR-dependent manner in cells infected at lower virus concentrations and in an IFNAR-independent manner in cells infected at higher virus concentrations. These differences in IFN subtype profiles in the 2 virus concentrations also resulted in distinct interferon-stimulated gene induction. These results present the novel finding that different viral MOIs differentially activate JAK/STAT signaling through the IFNAR, which greatly affects the profile of IFN subtypes that are induced.
IMPORTANCE
Type I IFNs are pleiotropic cytokines that are instrumental in combating viral diseases. Understanding how the individual subtypes are induced is important in developing strategies to block viral replication. Many studies have reported that different viruses induce distinct type I IFN subtype profiles due to differences in the way viruses are sensed in different cell types. However, we report in our study the novel finding that the amount of virus used to infect a system can also affect which type I IFN subtypes are induced due to the extent of activation of certain signaling pathways. These distinct IFN subtype profiles in cells infected at different MOIs are correlated with differences in interferon-stimulated gene induction, indicating that the same virus can induce distinct antiviral responses depending on the MOI. Because type I IFNs are used as therapeutic agents to treat viral diseases, understanding their antiviral mechanisms can enhance clinical treatments.
C1 [Zaritsky, Luna A.; Bedsaul, Jacquelyn R.; Zoon, Kathryn C.] NIAID, Cytokine Biol Sect, Div Intramural Res, NIH, Bethesda, MD 20892 USA.
RP Zoon, KC (reprint author), NIAID, Cytokine Biol Sect, Div Intramural Res, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM KZoon@niaid.nih.gov
FU Division of Intramural Research (DIR) at the National Institute of
Allergy and Infectious Diseases (NIAID), National Institutes of Health
(NIH); Intramural Research Training Program (IRTA)
FX This work was supported by the Intramural Research Training Program
(IRTA) and the Division of Intramural Research (DIR) at the National
Institute of Allergy and Infectious Diseases (NIAID), National
Institutes of Health (NIH).
NR 30
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 0022-538X
EI 1098-5514
J9 J VIROL
JI J. Virol.
PD NOV
PY 2015
VL 89
IS 22
BP 11534
EP 11548
DI 10.1128/JVI.01727-15
PG 15
WC Virology
SC Virology
GA CU4AC
UT WOS:000363467200030
PM 26355085
ER
PT J
AU Chien, WW
McDougald, DS
Roy, S
Fitzgerald, TS
Cunningham, LL
AF Chien, Wade W.
McDougald, Devin S.
Roy, Soumen
Fitzgerald, Tracy S.
Cunningham, Lisa L.
TI Cochlear gene transfer mediated by adeno-associated virus: Comparison of
two surgical approaches
SO LARYNGOSCOPE
LA English
DT Article
DE Gene therapy; adeno-associated virus; round window; cochleostomy;
hearing loss
ID GUINEA-PIG COCHLEA; IN-VIVO DELIVERY; HAIR-CELLS; TRANSGENE EXPRESSION;
MURINE COCHLEA; MOUSE; THERAPY; TRANSDUCTION; ADENOVIRUS; HEARING
AB Objectives/HypothesisGene therapy offers the possibility of delivering corrective genetic materials to the cochlea, potentially improving hearing. In animals, the most commonly used surgical methods for viral gene therapy delivery to the cochlea are the round window and the cochleostomy approaches. However, the patterns of viral infection and the effects on hearing have not been directly compared between these two approaches. In this study, we compare the patterns of cochlear infection and effects on hearing between these two surgical approaches using adeno-associated virus serotype 2/8 (AAV8) as the gene delivery vehicle.
Study DesignAnimal study and basic science research.
MethodsOne- to two-month-old CBA/J mice were used in this study. AAV8-green fluorescent protein (GFP) was delivered to the cochlea by either the round window or the cochleostomy approach (described below). Auditory brainstem response was used to examine hearing thresholds before and after surgery. Animals were examined at 1, 2, 3, and 4 weeks after surgery for the patterns of cochlear infection and hearing loss.
ResultsCochlear gene transfer was successful through both surgical approaches. In both approaches, AAV8-GFP mostly infected the inner hair cells. There was occasional low-level infection of the outer hair cells and supporting cells. The two surgical approaches resulted in comparable viral infection efficiencies. The round window approach resulted in less surgical trauma, as indicated by hearing loss, than the cochleostomy approach.
ConclusionsAdeno-associated virus-mediated gene transfer to the cochlea can be accomplished using either the round window or the cochleostomy surgical approach. The round window approach resulted in less hearing loss compared to the cochleostomy approach.
C1 [Chien, Wade W.; McDougald, Devin S.; Roy, Soumen; Fitzgerald, Tracy S.; Cunningham, Lisa L.] Natl Inst Deafness & Other Commun Disorders, NIH, Bethesda, MD USA.
[Chien, Wade W.] Johns Hopkins Sch Med, Dept Otolaryngol Head & Neck Surg, Baltimore, MD USA.
RP Chien, WW (reprint author), Johns Hopkins Hlth Care & Surg Ctr, 6420 Rockledge Dr,Suite 4920, Bethesda, MD 20817 USA.
EM wchien1@jhmi.edu
FU National Institute on Deafness and Other Communication Disorders
[Z01-DC-000079-03, Z01-DC-000082-02]
FX This study was supported by National Institute on Deafness and Other
Communication Disorders intramural research funds Z01-DC-000079-03
(L.L.C.) and Z01-DC-000082-02 (W.W.C)
NR 22
TC 2
Z9 2
U1 1
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0023-852X
EI 1531-4995
J9 LARYNGOSCOPE
JI Laryngoscope
PD NOV
PY 2015
VL 125
IS 11
BP 2557
EP 2564
DI 10.1002/lary.25317
PG 8
WC Medicine, Research & Experimental; Otorhinolaryngology
SC Research & Experimental Medicine; Otorhinolaryngology
GA CU2XO
UT WOS:000363387200033
PM 25891801
ER
PT J
AU Park, JW
Park, DM
Choi, BK
Kwon, BS
Seong, JK
Green, JE
Kim, DY
Kim, HK
AF Park, Jun Won
Park, Dong Min
Choi, Beom K.
Kwon, Byoung S.
Seong, Je Kyung
Green, Jeffrey E.
Kim, Dae-Yong
Kim, Hark Kyun
TI Establishment and characterization of metastatic gastric cancer cell
lines from murine gastric adenocarcinoma lacking Smad4, p53, and
E-cadherin
SO MOLECULAR CARCINOGENESIS
LA English
DT Article
DE cell line; EMT; gastric cancer; mouse; beta-catenin pathway
ID MOUSE MODEL; STOMACH
AB There is a strong need for murine gastric cancer cell line models recapitulating human gastric cancers. Here, we describe two murine gastric cancer cell lines designated as NCC-S1 and NCC-S3. They were generated from gastric adenocarcinomas that formed in a Villin-cre, Smad4(F/F), Trp53(F/F), Cdh1(F/wt) mouse and a Pdx1-cre, Trp53(F/F), Cdh1(F/F) mouse, respectively. Molecular profiles of both cell lines were very similar to human gastric cancer. NCC-S1M and NCC-S3M subpopulation clones were isolated from pulmonary metastasis of heterotopic allografts of NCC-S1 and NCC-S3 cells, respectively. NCC-S1M and NCC-S3M showed enhanced in vivo growth rates and metastatic potentials and exhibited epithelial-to-mesenchymal transition features. NCC-S1M cells developed orthotopic and heterotopic tumors in immunocompetent mice in predictable manner, and were useful for testing the efficacy of an immunotherapeutic agent, anti-4-1BB antibody. NCC-S1M and NCC-S3M cells demonstrated Wnt/-catenin pathway activation, and knockdown of Ctnnb1 reversed the metastatic phenotype of NCC-S1M. These results underscore the role of Wnt/-catenin pathway in metastatic phenotype of gastric cancer. Taken together, our novel metastatic gastric cancer cell lines are useful resources for drug development and metastasis research. (c) 2014 Wiley Periodicals, Inc.
C1 [Park, Jun Won; Park, Dong Min; Choi, Beom K.; Kwon, Byoung S.; Kim, Hark Kyun] Natl Canc Ctr, Goyang, Gyeonggi, South Korea.
[Park, Jun Won; Seong, Je Kyung; Kim, Dae-Yong] Seoul Natl Univ, Coll Vet Med, Seoul 151742, South Korea.
[Green, Jeffrey E.] NCI, Lab Canc Biol & Genet, Bethesda, MD 20892 USA.
RP Kim, DY (reprint author), Seoul Natl Univ, Dept Vet Pathol, Coll Vet Med, 599 Gwanank Ro, Seoul 151742, South Korea.
FU National Cancer Center [1210051, 1410850]; Proteogenomic Research
Program
FX Grant sponsor: National Cancer Center; Grant numbers: 1210051; 1410850;
Grant sponsor: Proteogenomic Research Program
NR 15
TC 2
Z9 2
U1 0
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0899-1987
EI 1098-2744
J9 MOL CARCINOGEN
JI Mol. Carcinog.
PD NOV
PY 2015
VL 54
IS 11
BP 1521
EP 1527
DI 10.1002/mc.22226
PG 7
WC Biochemistry & Molecular Biology; Oncology
SC Biochemistry & Molecular Biology; Oncology
GA CU0PX
UT WOS:000363220700027
PM 25307412
ER
PT J
AU Frederick, AL
Yano, H
Trifilieff, P
Vishwasrao, HD
Biezonski, D
Meszaros, J
Urizar, E
Sibley, DR
Kellendonk, C
Sonntag, KC
Graham, DL
Colbran, RJ
Stanwood, GD
Javitch, JA
AF Frederick, A. L.
Yano, H.
Trifilieff, P.
Vishwasrao, H. D.
Biezonski, D.
Meszaros, J.
Urizar, E.
Sibley, D. R.
Kellendonk, C.
Sonntag, K. C.
Graham, D. L.
Colbran, R. J.
Stanwood, G. D.
Javitch, J. A.
TI Evidence against dopamine D1/D2 receptor heteromers
SO MOLECULAR PSYCHIATRY
LA English
DT Article
ID MEDIUM SPINY NEURONS; BAC TRANSGENIC MICE; ADENYLATE-CYCLASE; BASAL
GANGLIA; RAT STRIATUM; PHOSPHOINOSITIDE HYDROLYSIS; COMPARTMENTAL
ORGANIZATION; NUCLEUS-ACCUMBENS; PHOSPHOLIPASE-C; GENE-EXPRESSION
AB Hetero-oligomers of G-protein-coupled receptors have become the subject of intense investigation, because their purported potential to manifest signaling and pharmacological properties that differ from the component receptors makes them highly attractive for the development of more selective pharmacological treatments. In particular, dopamine D1 and D2 receptors have been proposed to form hetero-oligomers that couple to G(alpha q) proteins, and SKF83959 has been proposed to act as a biased agonist that selectively engages these receptor complexes to activate G(alpha q) and thus phospholipase C. D1/D2 heteromers have been proposed as relevant to the pathophysiology and treatment of depression and schizophrenia. We used in vitro bioluminescence resonance energy transfer, ex vivo analyses of receptor localization and proximity in brain slices, and behavioral assays in mice to characterize signaling from these putative dimers/oligomers. We were unable to detect G(alpha q) or G(alpha 11) protein coupling to homomers or heteromers of D1 or D2 receptors using a variety of biosensors. SKF83959-induced locomotor and grooming behaviors were eliminated in D1 receptor knockout (KO) mice, verifying a key role for D1-like receptor activation. In contrast, SKF83959-induced motor responses were intact in D2 receptor and G(alpha q) KO mice, as well as in knock-in mice expressing a mutant Ala(286)-CaMKII alpha that cannot autophosphorylate to become active. Moreover, we found that, in the shell of the nucleus accumbens, even in neurons in which D1 and D2 receptor promoters are both active, the receptor proteins are segregated and do not form complexes. These data are not compatible with SKF83959 signaling through G(alpha q) or through a D1/D2 heteromer and challenge the existence of such a signaling complex in the adult animals that we used for our studies.
C1 [Frederick, A. L.] Vanderbilt Univ, Sch Med, Grad Program Neurosci, Nashville, TN 37232 USA.
[Yano, H.; Biezonski, D.; Meszaros, J.; Urizar, E.; Kellendonk, C.; Javitch, J. A.] Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY 10025 USA.
[Yano, H.; Biezonski, D.; Meszaros, J.; Urizar, E.; Kellendonk, C.; Javitch, J. A.] Columbia Univ, Coll Phys & Surg, Dept Pharmacol, New York, NY 10025 USA.
[Trifilieff, P.] Univ Bordeaux, INRA UMR 1286, Nutr & Integrat Neurobiol, Bordeaux, France.
[Trifilieff, P.; Vishwasrao, H. D.] Columbia Univ, Dept Neurosci, New York, NY USA.
[Sibley, D. R.] Natl Inst Neurol Disorders & Stroke, NIH, Mol Neuropharmacol Sect, Bethesda, MD USA.
[Kellendonk, C.; Javitch, J. A.] New York State Psychiat Inst & Hosp, Div Mol Therapeut, New York, NY 10032 USA.
[Sonntag, K. C.] Harvard Univ, Sch Med, McLean Hosp, Dept Psychiat, Belmont, MA 02178 USA.
[Graham, D. L.; Stanwood, G. D.] Vanderbilt Univ, Sch Med, Dept Pharmacol, Nashville, TN 37232 USA.
[Colbran, R. J.] Vanderbilt Univ, Sch Med, Dept Mol Physiol & Biophys, Nashville, TN 37212 USA.
[Colbran, R. J.; Stanwood, G. D.] Vanderbilt Univ, Sch Med, Vanderbilt Kennedy Ctr, Nashville, TN 37212 USA.
[Colbran, R. J.; Stanwood, G. D.] Vanderbilt Univ, Sch Med, Vanderbilt Brain Inst, Nashville, TN 37212 USA.
RP Stanwood, GD (reprint author), Vanderbilt Univ, Sch Med, Dept Pharmacol, 8405 MRBIV,2213 Garland Ave, Nashville, TN 37232 USA.
EM gregg.stanwood@vanderbilt.edu; jaj2@columbia.edu
FU NIH [RO1MH086629, F31DA029499, TL1 RR024158-04, K05DA022413, R01MH54137,
RO1MH093672, R01NS078291]; Research Foundation for Mental Hygiene;
Lieber Center for Schizophrenia Research and Treatment; [P30HD15052]
FX This work was supported by NIH grants RO1MH086629 (GDS), F31DA029499 (to
ALF), TL1 RR024158-04 (to HY), K05DA022413 and R01MH54137 (to JAJ),
RO1MH093672 (to CK), R01NS078291 (to RJC), a Research scientist award
from the Research Foundation for Mental Hygiene (to PT) and the Lieber
Center for Schizophrenia Research and Treatment. Behavioral work was
performed at the Vanderbilt Mouse Neurobehavioral Core, which is
supported in part by P30HD15052. We thank Dr Celine Gales (Institut
National de la Sante et de la Recherche Medicale, Toulouse, France) and
Dr Nevin Lambert (Georgia Health Sciences University, Augusta, Georgia)
for kindly sharing Rluc and Venus fusion G protein constructs, Dr Stefan
Offermanns (University of Heidelberg, Germany) for supplying the
Galpha q mutant line and Dr Nicole Calakos (Duke University)
for the Drd1a-tdTomato reporter line. We also thank Matt Buendia,
Heather Durai and Dr John Allison for excellent technical assistance.
NR 70
TC 19
Z9 19
U1 0
U2 9
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1359-4184
EI 1476-5578
J9 MOL PSYCHIATR
JI Mol. Psychiatr.
PD NOV
PY 2015
VL 20
IS 11
BP 1373
EP 1385
DI 10.1038/mp.2014.166
PG 13
WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry
SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry
GA CU3ZK
UT WOS:000363465300012
PM 25560761
ER
PT J
AU Yang, J
Wang, S
Yang, Z
Hodgkinson, CA
Iarikova, P
Ma, JZ
Payne, TJ
Goldman, D
Li, MD
AF Yang, J.
Wang, S.
Yang, Z.
Hodgkinson, C. A.
Iarikova, P.
Ma, J. Z.
Payne, T. J.
Goldman, D.
Li, M. D.
TI The contribution of rare and common variants in 30 genes to risk
nicotine dependence
SO MOLECULAR PSYCHIATRY
LA English
DT Article
ID AFRICAN-AMERICAN SMOKERS; RECEPTOR SUBUNIT NR3A; YOUNG-WOMEN SMOKE;
SIGNIFICANT ASSOCIATION; EUROPEAN-AMERICANS; NMDA-RECEPTOR; FUNCTIONAL
POLYMORPHISM; GLUTAMATE-RECEPTOR; PROTEIN FUNCTION; LOW-FREQUENCY
AB Genetic and functional studies have revealed that both common and rare variants of several nicotinic acetylcholine receptor subunits are associated with nicotine dependence (ND). In this study, we identified variants in 30 candidate genes including nicotinic receptors in 200 sib pairs selected from the Mid-South Tobacco Family population with equal numbers of African Americans (AAs) and European Americans (EAs). We selected 135 of the rare and common variants and genotyped them in the Mid-South Tobacco Case-Control (MSTCC) population, which consists of 3088 AAs and 1430 EAs. None of the genotyped common variants showed significant association with smoking status (smokers vs non-smokers), Fagerstrom Test for ND scores or indexed cigarettes per day after Bonferroni correction. Rare variants in NRXN1, CHRNA9, CHRNA2, NTRK2, GABBR2, GRIN3A, DNM1, NRXN2, NRXN3 and ARRB2 were significantly associated with smoking status in the MSTCC AA sample, with weighted sum statistic (WSS) P-values ranging from 2.42 x 10(-3) to 1.31 x 10(-4) after 106 phenotype rearrangements. We also observed a significant excess of rare nonsynonymous variants exclusive to EA smokers in NRXN1, CHRNA9, TAS2R38, GRIN3A, DBH, ANKK1/DRD2, NRXN3 and CDH13 with WSS P-values between 3.5 x 10(-5) and 1 x 10(-6). Variants rs142807401 (A432T) and rs139982841 (A452V) in CHRNA9 and variants V132L, V389L, rs34755188 (R480H) and rs75981117 (N549S) in GRIN3A are of particular interest because they are found in both the AA and EA samples. A significant aggregate contribution of rare and common coding variants in CHRNA9 to the risk for ND (SKAT-C: P = 0.0012) was detected by applying the combined sum test in MSTCC EAs. Together, our results indicate that rare variants alone or combined with common variants in a subset of 30 biological candidate genes contribute substantially to the risk of ND.
C1 [Yang, J.; Wang, S.; Yang, Z.; Li, M. D.] Univ Virginia, Dept Psychiat & Neurobehav Sci, Charlottesville, VA 22903 USA.
[Hodgkinson, C. A.; Iarikova, P.; Goldman, D.] NIAAA, Lab Neurogenet, NIH, Bethesda, MD USA.
[Ma, J. Z.] Univ Virginia, Dept Publ Hlth Sci, Charlottesville, VA USA.
[Payne, T. J.] Univ Mississippi, Med Ctr, Dept Otolaryngol & Communicat Sci, ACT Ctr Tobacco Treatment Educ & Res, Jackson, MS 39216 USA.
RP Li, MD (reprint author), Univ Virginia, Dept Psychiat & Neurobehav Sci, 450 Ray C Hunt Dr, Charlottesville, VA 22903 USA.
EM ml2km@virginia.edu
RI Goldman, David/F-9772-2010
OI Goldman, David/0000-0002-1724-5405
FU National Institutes of Health [R01 DA012844]
FX We acknowledge the invaluable contributions of personal information and
blood samples by all participants in the study. This project was
supported by National Institutes of Health grant R01 DA012844 to MDL.
NR 67
TC 9
Z9 9
U1 1
U2 11
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1359-4184
EI 1476-5578
J9 MOL PSYCHIATR
JI Mol. Psychiatr.
PD NOV
PY 2015
VL 20
IS 11
BP 1467
EP 1478
DI 10.1038/mp.2014.156
PG 12
WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry
SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry
GA CU3ZK
UT WOS:000363465300021
PM 25450229
ER
PT J
AU Arrowsmith, CH
Audia, JE
Austin, C
Baell, J
Bennett, J
Blagg, J
Bountra, C
Brennan, PE
Brown, PJ
Bunnage, ME
Buser-Doepner, C
Campbell, RM
Carter, AJ
Cohen, P
Copeland, RA
Cravatt, B
Dahlin, JL
Dhanak, D
Edwards, AM
Frederiksen, M
Frye, SV
Gray, N
Grimshaw, CE
Hepworth, D
Howe, T
Huber, KVM
Jin, J
Knapp, S
Kotz, JD
Kruger, RG
Lowe, D
Mader, MM
Marsden, B
Mueller-Fahrnow, A
Muller, S
O'Hagan, RC
Overington, JP
Owen, DR
Rosenberg, SH
Ross, R
Roth, B
Schapira, M
Schreiber, SL
Shoichet, B
Sundstrom, M
Superti-Furga, G
Taunton, J
Toledo-Sherman, L
Walpole, C
Walters, MA
Willson, TM
Workman, P
Young, RN
Zuercher, WJ
AF Arrowsmith, Cheryl H.
Audia, James E.
Austin, Christopher
Baell, Jonathan
Bennett, Jonathan
Blagg, Julian
Bountra, Chas
Brennan, Paul E.
Brown, Peter J.
Bunnage, Mark E.
Buser-Doepner, Carolyn
Campbell, Robert M.
Carter, Adrian J.
Cohen, Philip
Copeland, Robert A.
Cravatt, Ben
Dahlin, Jayme L.
Dhanak, Dashyant
Edwards, Aled M.
Frederiksen, Mathias
Frye, Stephen V.
Gray, Nathanael
Grimshaw, Charles E.
Hepworth, David
Howe, Trevor
Huber, Kilian V. M.
Jin, Jian
Knapp, Stefan
Kotz, Joanne D.
Kruger, Ryan G.
Lowe, Derek
Mader, Mary M.
Marsden, Brian
Mueller-Fahrnow, Anke
Mueller, Susanne
O'Hagan, Ronan C.
Overington, John P.
Owen, Dafydd R.
Rosenberg, Saul H.
Ross, Ruth
Roth, Bryan
Schapira, Matthieu
Schreiber, Stuart L.
Shoichet, Brian
Sundstroem, Michael
Superti-Furga, Giulio
Taunton, Jack
Toledo-Sherman, Leticia
Walpole, Chris
Walters, Michael A.
Willson, Timothy M.
Workman, Paul
Young, Robert N.
Zuercher, William J.
TI The promise and peril of chemical probes (vol 11, pg 536, 2015)
SO NATURE CHEMICAL BIOLOGY
LA English
DT Correction
C1 [Roth, Bryan] Univ N Carolina, Sch Med, Natl Inst Mental Hlth, Psychoact Act Drug Screening Program NIMH PDSP,De, Chapel Hill, NC USA.
[Roth, Bryan] Univ N Carolina, UNC Eshelman Sch Pharm, Div Chem Biol & Med Chem, Chapel Hill, NC USA.
[Frederiksen, Mathias] Novartis, Novartis Inst BioMed Res, Basel, Switzerland.
RI Baell, Jonathan/E-5844-2017
OI Baell, Jonathan/0000-0003-2114-8242
FU Cancer Research UK [11566]
NR 1
TC 3
Z9 3
U1 7
U2 18
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1552-4450
EI 1552-4469
J9 NAT CHEM BIOL
JI Nat. Chem. Biol.
PD NOV
PY 2015
VL 11
IS 11
BP 887
EP 887
DI 10.1038/nchembio.1931
PG 1
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA CU1HS
UT WOS:000363272100017
PM 26485080
ER
PT J
AU Beringer, DX
Kleijwegt, FS
Wiede, F
van der Slik, AR
Loh, KL
Petersen, J
Dudek, NL
Duinkerken, G
Laban, S
Joosten, A
Vivian, JP
Chen, ZJ
Uldrich, AP
Godfrey, DI
McCluskey, J
Price, DA
Radford, KJ
Purcell, AW
Nikolic, T
Reid, HH
Tiganis, T
Roep, BO
Rossjohn, J
AF Beringer, Dennis X.
Kleijwegt, Fleur S.
Wiede, Florian
van der Slik, Arno R.
Loh, Khai Lee
Petersen, Jan
Dudek, Nadine L.
Duinkerken, Gaby
Laban, Sandra
Joosten, Antoinette
Vivian, Julian P.
Chen, Zhenjun
Uldrich, Adam P.
Godfrey, Dale I.
McCluskey, James
Price, David A.
Radford, Kristen J.
Purcell, Anthony W.
Nikolic, Tatjana
Reid, Hugh H.
Tiganis, Tony
Roep, Bart O.
Rossjohn, Jamie
TI T cell receptor reversed polarity recognition of a self-antigen major
histocompatibility complex
SO NATURE IMMUNOLOGY
LA English
DT Article
ID HUMAN DENDRITIC CELLS; STRUCTURAL BASIS; THYMIC SELECTION; GERMLINE
BIAS; AMINO-ACIDS; CLASS-I; MHC; TCR; PEPTIDE; TOLERANCE
AB Central to adaptive immunity is the interaction between the alpha beta T cell receptor (TCR) and peptide presented by the major histocompatibility complex (MHC) molecule. Presumably reflecting TCR-MHC bias and T cell signaling constraints, the TCR universally adopts a canonical polarity atop the MHC. We report the structures of two TCRs, derived from human induced T regulatory (iT(reg)) cells, complexed to an MHC class II molecule presenting a proinsulin-derived peptide. The ternary complexes revealed a 1800 polarity reversal compared to all other TCR-peptide-MHC complex structures. Namely, the iT(reg) TCR alpha-chain and beta-chain are overlaid with the alpha-chain and beta-chain of MHC class II, respectively. Nevertheless, this TCR interaction elicited a peptide-reactive, MHC-restricted T cell signal. Thus TCRs are not 'hardwired' to interact with MHC molecules in a stereotypic manner to elicit a T cell signal, a finding that fundamentally challenges our understanding of TCR recognition.
C1 [Beringer, Dennis X.; Wiede, Florian; Loh, Khai Lee; Petersen, Jan; Dudek, Nadine L.; Vivian, Julian P.; Purcell, Anthony W.; Reid, Hugh H.; Tiganis, Tony; Rossjohn, Jamie] Monash Univ, Infect & Immun Program, Biomed Discovery Inst, Clayton, Vic, Australia.
[Beringer, Dennis X.; Wiede, Florian; Loh, Khai Lee; Petersen, Jan; Dudek, Nadine L.; Vivian, Julian P.; Purcell, Anthony W.; Reid, Hugh H.; Tiganis, Tony; Rossjohn, Jamie] Monash Univ, Dept Biochem & Mol Biol, Biomed Discovery Inst, Clayton, Vic, Australia.
[Kleijwegt, Fleur S.; van der Slik, Arno R.; Duinkerken, Gaby; Laban, Sandra; Joosten, Antoinette; Nikolic, Tatjana; Roep, Bart O.] Leiden Univ, Med Ctr, Dept Immunohematol & Blood Transfus, Leiden, Netherlands.
[Petersen, Jan; Vivian, Julian P.; Reid, Hugh H.; Rossjohn, Jamie] Monash Univ, Australian Res Council Ctr Excellence Adv Mol Ima, Clayton, Vic, Australia.
[Chen, Zhenjun; Uldrich, Adam P.; Godfrey, Dale I.; McCluskey, James] Univ Melbourne, Australian Res Council Ctr Excellence Adv Mol Ima, Parkville, Vic 3052, Australia.
[Uldrich, Adam P.; Godfrey, Dale I.] Univ Melbourne, Dept Microbiol & Immunol, Peter Doherty Inst Infect & Immun, Parkville, Vic 3052, Australia.
[Price, David A.; Rossjohn, Jamie] Cardiff Univ, Sch Med, Inst Infect & Immun, Cardiff CF10 3AX, S Glam, Wales.
[Price, David A.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Radford, Kristen J.] Univ Queensland, Mater Res Inst, Brisbane, Qld, Australia.
[Radford, Kristen J.] Univ Queensland, Sch Biomed Sci, Brisbane, Qld, Australia.
RP Reid, HH (reprint author), Monash Univ, Infect & Immun Program, Biomed Discovery Inst, Clayton, Vic, Australia.
EM tony.tiganis@monash.edu; B.O.Roep@lumc.nl; jamie.rossjohn@monash.edu
RI Price, David/C-7876-2013; McCluskey, James/A-1291-2007;
OI Price, David/0000-0001-9416-2737; McCluskey, James/0000-0002-8597-815X;
Purcell, Anthony/0000-0003-0532-8331; Rossjohn,
Jamie/0000-0002-2020-7522
FU Australian Research Council (ARC); National Health and Medical Research
Council of Australia (NHMRC); Netherlands Organization for Scientific
Research [VICI 918.86.611]; European Union [241447]; National Diabetes
Expert Center - Dutch Diabetes Research Foundation (DEN); Diabetes
Research Netherlands (DON) Foundation
FX We thank staff at the Australian synchrotron, the Leiden University
Medical Center, the Monash Macromolecular Crystallization Facility, T.
Beddoe, J. Teeler, C. van der Torren, S. Scally, M. Tran, S. Gras, K.
Ladell, G. Dolton, R. Ayala-Perez and R. Berry for assistance. This work
was supported by the Australian Research Council (ARC) and the National
Health and Medical Research Council of Australia (NHMRC). A.P.U. is an
ARC Future Fellow, D.I.G. is an NHMRC Senior Principal Research Fellow,
D.A.P. is a Wellcome Trust Senior Investigator, K.J.R. is an NHMRC
Career Development Fellow, A.W.P. is an NHMRC Senior Research Fellow,
T.T. is an NHMRC Principal Research Fellow and K.J.R. is an NHMRC
Australia Fellow. F.S.K., A.J. and B.O.R. are supported by the
Netherlands Organization for Scientific Research (VICI 918.86.611), T.N.
and S.L. are supported by the European Union 7th Framework Program
(FP7/2007-2013) under Grant No. 241447 (Novel Immunotherapies for Type I
Diabetes (NIAMIT)) and G.D. and A.R.v.d.S. are supported by the National
Diabetes Expert Center funded by the Dutch Diabetes Research Foundation
(DFN) and the Diabetes Research Netherlands (DON) Foundation.
NR 39
TC 21
Z9 23
U1 4
U2 24
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1529-2908
EI 1529-2916
J9 NAT IMMUNOL
JI Nat. Immunol.
PD NOV
PY 2015
VL 16
IS 11
BP 1153
EP 1161
DI 10.1038/ni.3271
PG 9
WC Immunology
SC Immunology
GA CT8VW
UT WOS:000363096000009
PM 26437244
ER
PT J
AU Heindel, JJ
Newbold, R
Schug, TT
AF Heindel, Jerrold J.
Newbold, Retha
Schug, Thaddeus T.
TI Endocrine disruptors and obesity
SO NATURE REVIEWS ENDOCRINOLOGY
LA English
DT Review
ID EPIGENETIC TRANSGENERATIONAL INHERITANCE; POLYBROMINATED DIPHENYL
ETHERS; EARLY-LIFE EXPOSURE; MESENCHYMAL STEM-CELLS; BISPHENOL-A
EXPOSURE; ORAL DOSE TOXICITY; IN-UTERO EXPOSURE; AIR-POLLUTION; PRENATAL
EXPOSURE; BODY-WEIGHT
AB The increasing incidence of obesity is a serious global public health challenge. Although the obesity epidemic is largely fueled by poor nutrition and lack of exercise, certain chemicals have been shown to potentially have a role in its aetiology. A substantial body of evidence suggests that a subclass of endocrine-disrupting chemicals (EDCs), which interfere with endocrine signalling, can disrupt hormonally regulated metabolic processes, especially if exposure occurs during early development. These chemicals, so-called 'obesogens' might predispose some individuals to gain weight despite their efforts to limit caloric intake and increase levels of physical activity. This Review discusses the role of EDCs in the obesity epidemic, the latest research on the obesogen concept, epidemiological and experimental findings on obesogens, and their modes of action. The research reviewed here provides knowledge that health scientists can use to inform their research and decision-making processes.
C1 [Heindel, Jerrold J.; Schug, Thaddeus T.] Natl Inst Environm Sci, Div Extramural Res & Training, Populat Hlth Branch, Res Triangle Pk, NC 27709 USA.
[Newbold, Retha] Natl Inst Environm Hlth Sci, Div Natl Toxicol Program, Natl Inst Hlth, Res Triangle Pk, NC 27709 USA.
RP Heindel, JJ (reprint author), Natl Inst Environm Sci, Div Extramural Res & Training, Populat Hlth Branch, POB 12233, Res Triangle Pk, NC 27709 USA.
EM J.J.H.heindelj@niehs.nih.gov
NR 139
TC 25
Z9 25
U1 17
U2 85
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1759-5029
EI 1759-5037
J9 NAT REV ENDOCRINOL
JI Nat. Rev. Endocrinol.
PD NOV
PY 2015
VL 11
IS 11
BP 653
EP 661
DI 10.1038/nrendo.2015.163
PG 9
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA CU4CQ
UT WOS:000363474400008
PM 26391979
ER
PT J
AU Metti, AL
Aizenstein, H
Yaffe, K
Boudreau, RM
Newman, A
Launer, L
Gianaros, PJ
Lopez, OL
Saxton, J
Ives, DG
Kritchevsky, S
Vallejo, AN
Rosano, C
AF Metti, Andrea L.
Aizenstein, Howard
Yaffe, Kristine
Boudreau, Robert M.
Newman, Anne
Launer, Lenore
Gianaros, Peter J.
Lopez, Oscar L.
Saxton, Judith
Ives, Diane G.
Kritchevsky, Stephen
Vallejo, Abbe N.
Rosano, Caterina
TI Trajectories of peripheral interleukin-6, structure of the hippocampus,
and cognitive impairment over 14 years in older adults
SO NEUROBIOLOGY OF AGING
LA English
DT Article
DE Cognitive impairment; Interleukin-6; Hippocampal morphology; Aging;
Epidemiology
ID C-REACTIVE PROTEIN; TUMOR-NECROSIS-FACTOR; CARDIOVASCULAR HEALTH;
ALZHEIMERS-DISEASE; INFLAMMATORY MARKERS; BRAIN; RISK; DECLINE; MEMORY;
IL-6
AB We aimed to investigate if trajectory components (baseline level, slope, and variability) of peripheral interleukin-6 (IL-6) over time were related to cognitive impairment and smaller hippocampal volume and if hippocampal volume explained the associations between IL-6 and cognitive impairment. Multivariable regression models were used to test the association between IL-6 trajectory components with change in neuroimaging measures of the hippocampus and with cognitive impairment among 135 older adults (70-79 years at baseline) from the Healthy Brain Project over 14 years. IL-6 variability was positively associated with cognitive impairment (odds ratio [OR] = 5.86, 95% confidence interval [CI]: 1.24, 27.61) and with greater decrease per year of gray matter volume of the hippocampus (beta = -0.008, standard error = 0.004, p = 0.03). After adjustment for hippocampal volume, the OR of cognitive impairment decreased for each unit of IL-6 variability and CIs widened (OR = 4.36, 95% CI: 0.67, 28.29). Neither baseline levels nor slopes of IL-6 were related to cognitive impairment or hippocampal volume. We believe this has potential clinical and public health implications by suggesting adults with stable levels of peripheral IL-6 may be better targets for intervention studies for slowing or preventing cognitive decline. (C) 2015 Elsevier Inc. All rights reserved.
C1 [Metti, Andrea L.] Metti Consulting Co, Pittsburgh, PA 15207 USA.
[Aizenstein, Howard] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA.
[Yaffe, Kristine] Univ Calif San Francisco, Dept Psychiat, San Francisco, CA USA.
[Yaffe, Kristine] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA.
[Yaffe, Kristine] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
[Boudreau, Robert M.; Newman, Anne; Ives, Diane G.; Rosano, Caterina] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA.
[Launer, Lenore] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
[Gianaros, Peter J.] Univ Pittsburgh, Dept Psychol, Pittsburgh, PA 15260 USA.
[Lopez, Oscar L.; Saxton, Judith] Univ Pittsburgh, Dept Neurol, Pittsburgh, PA 15260 USA.
[Kritchevsky, Stephen] Wake Forest Univ, Dept Internal Med, Winston Salem, NC 27109 USA.
[Vallejo, Abbe N.] Univ Pittsburgh, Sch Med, UPMC Childrens Hosp Pittsburgh, Div Pediat Rheumatol, Pittsburgh, PA USA.
[Vallejo, Abbe N.] Univ Pittsburgh, Sch Med, UPMC Childrens Hosp Pittsburgh, Dept Pediat & Immunol, Pittsburgh, PA USA.
RP Metti, AL (reprint author), Metti Consulting Co, 4216 Lydia St, Pittsburgh, PA 15207 USA.
EM andrealmetti@gmail.com
RI Newman, Anne/C-6408-2013;
OI Newman, Anne/0000-0002-0106-1150; Rosano, Caterina/0000-0002-0909-1506;
Rosano, Caterina/0000-0002-4271-6010; Boudreau,
Robert/0000-0003-0162-5187; Metti, Andrea/0000-0002-4467-5304
FU National Institute on Aging (NIA) [N01-AG-6-2101, N01-AG-6-2103,
N01-AG-6-2106, R01-AG028050, R01 AG028288]; National Institute of
Nursing Research (NINR) [R01-NR012459]; Intramural Research Program on
the National Institutes of Health (NIH), National Institute on Aging
FX This work was supported by National Institute on Aging (NIA) Contracts
N01-AG-6-2101; N01-AG-6-2103; N01-AG-6-2106; NIA grants R01-AG028050 and
R01 AG028288, and National Institute of Nursing Research (NINR) grant
R01-NR012459. This research was supported in part by the Intramural
Research Program on the National Institutes of Health (NIH), National
Institute on Aging.
NR 48
TC 2
Z9 2
U1 0
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0197-4580
EI 1558-1497
J9 NEUROBIOL AGING
JI Neurobiol. Aging
PD NOV
PY 2015
VL 36
IS 11
BP 3038
EP 3044
DI 10.1016/j.neurobiolaging.2015.07.025
PG 7
WC Geriatrics & Gerontology; Neurosciences
SC Geriatrics & Gerontology; Neurosciences & Neurology
GA CU1LA
UT WOS:000363281700014
PM 26279115
ER
PT J
AU Beydoun, MA
Beydoun, HA
Rostant, OS
Dore, GA
Fanelli-Kuczmarski, MT
Evans, MK
Zonderman, AB
AF Beydoun, May A.
Beydoun, Hind A.
Rostant, Ola S.
Dore, Greg A.
Fanelli-Kuczmarski, Marie T.
Evans, Michele K.
Zonderman, Alan B.
TI Thyroid hormones are associated with longitudinal cognitive change in an
urban adult population
SO NEUROBIOLOGY OF AGING
LA English
DT Article
DE Thyroid hormones; Cognitive function; Longitudinal studies; Aging
ID SUBCLINICAL HYPOTHYROIDISM; OLD-AGE; THYROXINE REPLACEMENT; STIMULATING
HORMONE; DEPRESSED MOOD; US ADULTS; HEALTHY; MEMORY; IMPAIRMENT;
DEMENTIA
AB Recent evidence indicates that thyroid hormones may be closely linked to cognition among adults. We investigated associations between thyroid hormones and longitudinal cognitive change, within and outside of reference ranges, stratifying by sex and race. This longitudinal study used data from the Healthy Aging in Neighborhoods of Diversity Across the Lifespan study, set in Baltimore City, MD, 2004-2013, on adults aged 30-64 years at baseline visit, with a length of follow-up between visits 1 and 2 ranging from < 1 to 8 years; mean +/- standard deviation: 4.64 +/- 0.93. The final analytic sample sizes ranged from 1486 to 1602 participants with 1.6-1.7 visits per participant (total visits: 2496-2757), depending on the cognitive test. Eleven cognitive test scores spanning domains of learning or memory, language or verbal, attention, visuospatial and/or visuoconstruction, psychomotor speed, executive function, and mental status were used. Mixed-effects regression models were conducted, interacting time of follow-up with several thyroid exposures. Whites performed better than African Americans, with only 4 cognitive test scores of 11 declining significantly over time. Importantly, above reference range thyroid stimulating hormone (vs. reference range, thyroid stimulating hormone, above reference range [TSHarr]) was linked to faster rates of decline on the digits span backwards test, reflecting working memory (TSHarr x time gamma +/- standard error: -0.14 +/- 0.05, p = 0.006) and clock-command, at test of visuospatial and/or visuoconstruction abilities (TSHarr x Time gamma +/- standard error: -0.10 +/- 0.04, p = 0.004). The latter finding was replicated when comparing normal thyroid function to " subclinical hypothyroidism". Within-reference ranges, a higher thyroid stimulating hormone was related to faster decline on the clock-command test scores in women. In sum, higher baseline thyroid stimulating hormone was associated with faster cognitive decline over-time among urban US adults, specifically in domains of working memory and visuospatial and/or visuoconstruction abilities. Published by Elsevier Inc.
C1 [Beydoun, May A.; Rostant, Ola S.; Dore, Greg A.; Evans, Michele K.; Zonderman, Alan B.] NIA, NIH, Biomed Res Ctr, IRP, Baltimore, MD 21224 USA.
[Beydoun, Hind A.] Eastern Virginia Med Sch, Grad Program Publ Hlth, Norfolk, VA 23501 USA.
[Fanelli-Kuczmarski, Marie T.] Univ Delaware, Dept Behav Hlth & Nutr, Newark, DE USA.
RP Beydoun, MA (reprint author), NIA, NIH, Biomed Res Ctr, IRP, 251 Bayview Blvd,Suite 100,Room 04B118, Baltimore, MD 21224 USA.
EM baydounm@mail.nih.gov
OI Zonderman, Alan B/0000-0002-6523-4778
FU National Institute on Aging, Intramural Research Program (NIA/NIH/IRP)
FX This study was entirely supported by the National Institute on Aging,
Intramural Research Program (NIA/NIH/IRP).
NR 47
TC 5
Z9 6
U1 2
U2 6
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0197-4580
EI 1558-1497
J9 NEUROBIOL AGING
JI Neurobiol. Aging
PD NOV
PY 2015
VL 36
IS 11
BP 3056
EP 3066
DI 10.1016/j.neurobiolaging.2015.08.002
PG 11
WC Geriatrics & Gerontology; Neurosciences
SC Geriatrics & Gerontology; Neurosciences & Neurology
GA CU1LA
UT WOS:000363281700016
PM 26329688
ER
PT J
AU Pereira, IT
Gallagher, M
Rapp, PR
AF Pereira, Ines Tomas
Gallagher, Michela
Rapp, Peter R.
TI Head west or left, east or right: interactions between memory systems in
neurocognitive aging
SO NEUROBIOLOGY OF AGING
LA English
DT Article
DE Prefrontal cortex; Hippocampus; Memory systems; Arc; Rat; Neuroadaptive
aging
ID SPATIAL-LEARNING IMPAIRMENT; MILD COGNITIVE IMPAIRMENT; EARLY GENE ARC;
CAUDATE-NUCLEUS; AGED RATS; NAVIGATION STRATEGIES; PREFRONTAL CORTEX;
WORKING-MEMORY; MESSENGER-RNA; ANIMAL-MODELS
AB Cognitive aging is accompanied by decline in multiple domains of memory. Here, we developed a T-maze task that required rats to learn competing hippocampal, and striatal navigation strategies in succession, across days. A final session increased demands on cognitive flexibility and required within-day switching between strategies, emphasizing capacities that engage the prefrontal cortex. Background characterization in young and aged rats used a water maze protocol optimized for individual differences in hippocampal integrity. Consistent with earlier work, young adults acquired place strategies in the T-maze faster than response, whereas the opposite was observed in aged rats with impaired spatial memory. The novel result was that aged animals with preserved spatial memory displayed a qualitatively distinct pattern, acquiring place and response strategies equally rapidly, without disruption when switching between them. Subsequent in situ hybridization for the plasticity-related immediate-early gene Arc revealed that while increasing demands on cognitive flexibility and within-day strategy switching potently engaged the prefrontal cortex in young adult and aged-impaired rats, Arc expression was insensitive in aged rats with normal spatial memory and superior switching abilities. Together, the results indicate that cognitive aging is an emergent property of the interactions between memory systems, and that successful cognitive outcomes reflect a distinct neuroadaptive process rather than a slower rate of aging. (C) 2015 Elsevier Inc. All rights reserved.
C1 [Pereira, Ines Tomas; Rapp, Peter R.] NIA, Neurocognit Aging Sect, Lab Behav Neurosci, NIH, Baltimore, MD 21224 USA.
[Gallagher, Michela] Johns Hopkins Univ, Dept Psychol & Brain Sci, Baltimore, MD USA.
RP Rapp, PR (reprint author), 251 Bayview Blvd,Suite 100,Room 9C224, Baltimore, MD 21224 USA.
EM rappp@mail.nih.gov
OI Tomas Pereira, Ines/0000-0003-2388-8164
FU NIH [AG09973]; NIA; Fundacao para a Ciencia e a Tecnologia
[SFRH/BD/27758/2006]
FX The authors would like to acknowledge Bonnie Fletcher, Pul Park, Rebecca
P. Haberman, Robert McMahan, and members of the Neurocognitive Aging
Section for helpful discussion and technical assistance. This research
was supported by NIH grant AG09973, the Intramural Research Program of
the NIA, and by grant SFRH/BD/27758/2006 from Fundacao para a Ciencia e
a Tecnologia.
NR 57
TC 2
Z9 2
U1 7
U2 11
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0197-4580
EI 1558-1497
J9 NEUROBIOL AGING
JI Neurobiol. Aging
PD NOV
PY 2015
VL 36
IS 11
BP 3067
EP 3078
DI 10.1016/j.neurobiolaging.2015.07.024
PG 12
WC Geriatrics & Gerontology; Neurosciences
SC Geriatrics & Gerontology; Neurosciences & Neurology
GA CU1LA
UT WOS:000363281700017
ER
PT J
AU Volkow, ND
Wang, GJ
Smith, L
Fowler, JS
Telang, F
Logan, J
Tomasi, D
AF Volkow, Nora D.
Wang, Gene-Jack
Smith, Lisa
Fowler, Joanna S.
Telang, Frank
Logan, Jean
Tomasi, Dardo
TI Recovery of dopamine transporters with methamphetamine detoxification is
not linked to changes in dopamine release
SO NEUROIMAGE
LA English
DT Article
DE Addiction; Neurotoxicity; Dopamine terminal; Parkinson's disease
ID POSITRON-EMISSION-TOMOGRAPHY; PLACEBO-CONTROLLED TRIAL;
PARKINSONS-DISEASE; DOWN-REGULATION; DOUBLE-BLIND; NEUROTOXICITY; BRAIN;
RAT; COCAINE; METHYLPHENIDATE
AB Methamphetamine's widepread abuse and concerns that it might increase Parkinson's disease led us to assess if the reported loss of dopamine transporters (DAT) in methamphetamine abusers (MA) reflected damage to dopamine neurons. Using PET with [C-11] cocaine to measure DAT, and with [C-11]raclopride to measure dopamine release (assessed as changes in specific binding of [C-11] raclopride between placebo and methylphenidate), which was used as a marker of dopamine neuronal function, we show that MA (n = 16), tested during early detoxification, had lower DAT (20-30%) but overall normal DA release in striatum(except for a small decrease in left putamen), when compared to controls (n = 15). In controls, DAT were positively correlated with DA release (higher DAT associated with larger DA increases), consistent with DAT serving as markers of DA terminals. In contrast, MA showed a trend for a negative correlation (p = 0.07) (higher DAT associated with lower DA increases), consistent with reduced DA re-uptake following DAT downregulation. MA who remained abstinent nine-months later (n = 9) showed significant increases in DAT (20%) but methylphenidate-induced dopamine increases did not change. In contrast, in controls, DAT did not change when retested 9 months later but methylphenidate-induced dopamine increases in ventral striatum were reduced (p = 0.05). Baseline D2/D3 receptors in caudate were lower in MA than in controls and did not change with detoxification, nor did they change in the controls upon retest. The loss of DAT in the MA, which was not associated with a concomitant reduction in dopamine release as would have been expected if DAT loss reflected DA terminal degneration; as well as the recovery of DAT after protracted detoxification, which was not associated with increased dopamine release as would have been expected if DAT increases reflected terminal regeneration, indicate that the loss of DAT in these MA does not reflect degeneration of dopamine terminals. Published by Elsevier Inc.
C1 [Volkow, Nora D.; Wang, Gene-Jack; Telang, Frank; Logan, Jean; Tomasi, Dardo] NIAAA, Lab Neuroimaging, Intramural Program, Bethesda, MD USA.
[Smith, Lisa] Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA USA.
[Fowler, Joanna S.] Brookhaven Natl Lab, Dept Med, Upton, NY 11973 USA.
[Volkow, Nora D.] NIDA, Off Director, Bethesda, MD 20892 USA.
RP Volkow, ND (reprint author), NIDA, NIH, 6001 Execut Blvd,Room 5274, Bethesda, MD 20892 USA.
EM nvolkow@nida.nih.gov
OI Logan, Jean/0000-0002-6993-9994
FU NIH intramural program (NIAAA); Brookhaven National Laboratory (BNL)
[DE-AC02-98CH10886]
FX This research was supported by the NIH intramural program (NIAAA) and
carried out at Brookhaven National Laboratory (BNL) under contract
DE-AC02-98CH10886. We thank C. Wong, C Shea, Y. Xu, D Alexoff, P. King,
Karen Apelskog and Ruben Baler.
NR 54
TC 9
Z9 9
U1 0
U2 9
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1053-8119
EI 1095-9572
J9 NEUROIMAGE
JI Neuroimage
PD NOV 1
PY 2015
VL 121
BP 20
EP 28
DI 10.1016/j.neuroimage.2015.07.035
PG 9
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA CT9FK
UT WOS:000363122000003
PM 26208874
ER
PT J
AU Paulsen, JL
Ozarslan, E
Komlosh, ME
Basser, PJ
Song, YQ
AF Paulsen, Jeffrey L.
Oezarslan, Evren
Komlosh, Michal E.
Basser, Peter J.
Song, Yi-Qiao
TI Detecting compartmental non-Gaussian diffusion with symmetrized
double-PFG MRI
SO NMR IN BIOMEDICINE
LA English
DT Article
DE non-Gaussian diffusion; Kurtosis; double wavevector; double diffusion
encoding; microscopic anisotropy; compartment shape anisotroy;
restricted diffusion; diffusion correlation
ID SPIN-ECHO; MAGNETIC-RESONANCE; GRADIENT; NMR; KURTOSIS; VECTOR; TENSOR;
ANISOTROPY
AB Diffusion in tissue and porous media is known to be non-Gaussian and has been used for clinical indications of stroke and other tissue pathologies. However, when conventional NMR techniques are applied to biological tissues and other heterogeneous materials, the presence of multiple compartments (pores) with different Gaussian diffusivities will also contribute to the measurement of non-Gaussian behavior. Here we present symmetrized double PFG (sd-PFG), which can separate these two contributions to non-Gaussian signal decay as having distinct angular modulation frequencies. In contrast to prior angular d-PFG methods, sd-PFG can unambiguously extract kurtosis as an oscillation from samples with isotropic or uniformly oriented anisotropic pores, and can generally extract a combination of compartmental anisotropy and kurtosis. The method further fixes its sensitivity with respect to the time dependence of the apparent diffusion coefficient. We experimentally demonstrate the measurement of the fourth cumulant (kurtosis) of diffusion and find it consistent with theoretical predictions. By enabling the unambiguous identification of contributions of compartmental kurtosis to the signal, sd-PFG has the potential to help identify the underlying micro-structural changes corresponding to current kurtosis based diagnostics, and act as a novel source of contrast to better resolve tissue micro-structure. Copyright (c) 2015 John Wiley & Sons, Ltd.
C1 [Paulsen, Jeffrey L.; Song, Yi-Qiao] Schlumberger Doll Res Ctr, Cambridge, MA 02139 USA.
[Oezarslan, Evren] Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiol, Boston, MA 02215 USA.
[Oezarslan, Evren; Komlosh, Michal E.; Basser, Peter J.] NICHD, Sect Tissue Biophys & Biomimet, PPITS, NIH, Bethesda, MD 20892 USA.
[Oezarslan, Evren; Komlosh, Michal E.] Uniformed Serv Univ Hlth Sci, Ctr Neurosci & Regenerat Med, Bethesda, MD 20814 USA.
[Oezarslan, Evren] Bogazici Univ, Dept Phys, TR-34342 Istanbul, Turkey.
RP Paulsen, JL (reprint author), Schlumberger Doll Res Ctr, Cambridge, MA 02139 USA.
EM JPaulsen2@slb.com
FU Department of Defense in the Center for Neuroscience and Regenerative
Medicine (CNRM); Henry M. Jackson Foundation (HJF); NIH [R01MH074794];
TUBITAK-EU Co-Funded Brain Circulation Scheme [114C015]; CNRM/HJF
[G189BH]; Intramural Research Program (IRP) of the Eunice Kennedy
Shriver National Institute of Child Health and Human Development (NICHD)
[HD000266]
FX Support for this work includes contributions from Schlumberger. Evren
Ozsarslan was supported by (i) the Department of Defense in the Center
for Neuroscience and Regenerative Medicine (CNRM) and the Henry M.
Jackson Foundation (HJF), (ii) NIH R01MH074794, and (iii) TUBITAK-EU
Co-Funded Brain Circulation Scheme, project 114C015. Michal Komlosh was
supported by a grant for "Clinical Double Pulsed Field Gradient (dPFG)
MRI for Mild TBI Assessment" under the auspices of the CNRM/HJF
(#G189BH). Peter Basser was supported by funds derived from the
Intramural Research Program (IRP) of the Eunice Kennedy Shriver National
Institute of Child Health and Human Development (NICHD) underHD000266
(2015) "Imaging Water Diffusion in the Brain and in Other Soft Tissues".
NR 29
TC 1
Z9 1
U1 3
U2 12
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 NOV
PY 2015
VL 28
IS 11
BP 1550
EP 1556
DI 10.1002/nbm.3363
PG 7
WC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy
SC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy
GA CU4AE
UT WOS:000363467400021
PM 26434812
ER
PT J
AU Chew, EY
Schachat, AP
AF Chew, Emily Y.
Schachat, Andrew P.
TI Should We Add Screening of Age-Related Macular Degeneration to Current
Screening Programs for Diabetic Retinopathy?
SO OPHTHALMOLOGY
LA English
DT Editorial Material
ID COST-EFFECTIVENESS; CLINICAL-TRIAL; EYE DISEASE; PREVALENCE; ZINC
C1 [Chew, Emily Y.] NEI, NIH, Bethesda, MD 20892 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
NR 16
TC 0
Z9 0
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0161-6420
EI 1549-4713
J9 OPHTHALMOLOGY
JI Ophthalmology
PD NOV
PY 2015
VL 122
IS 11
BP 2155
EP 2156
DI 10.1016/j.ophtha.2015.08.007
PG 2
WC Ophthalmology
SC Ophthalmology
GA CU4IQ
UT WOS:000363491800012
PM 26498078
ER
PT J
AU Kelly, KA
Hollingsworth, MA
Brand, RE
Liu, CH
Singh, VK
Srivastava, S
Wasan, AD
Yadav, D
Andersen, DK
AF Kelly, Kimberly A.
Hollingsworth, Michael A.
Brand, Randall E.
Liu, Christina H.
Singh, Vikesh K.
Srivastava, Sudhir
Wasan, Ajay D.
Yadav, Dhiraj
Andersen, Dana K.
TI Advances in Biomedical Imaging, Bioengineering, and Related Technologies
for the Development of Biomarkers of Pancreatic Disease Summary of a
National Institute of Diabetes and Digestive and Kidney Diseases and
National Institute of Biomedical Imaging and Bioengineering Workshop
SO PANCREAS
LA English
DT Article
DE biomarkers; chronic pancreatitis; pancreatic cancer; molecular imaging;
exosomes; circulating tumor cells
AB A workshop sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases and the National Institute of Biomedical Imaging and Bioengineering focused on research gaps and opportunities in the development of new biomarkers of pancreatic disease. The session was held on July 22, 2015, and structured into 6 sessions: 1) Introduction and Overview; 2) Keynote Address; 3) New Approaches to the Diagnosis of Chronic Pancreatitis; 4) Biomarkers of Pain and Inflammation; 5) New Approaches to the Detection of Pancreatic Cancer; and 6) Shed Exosomes, Shed Cells, and Shed Proteins. Recent advances in the fields of pancreatic imaging, functional markers of pancreatic disease, proteomics, molecular and cellular imaging, and detection of circulating cancer cells and exosomes were reviewed. Knowledge gaps and research needs were highlighted. The development of new methods for the noninvasive determination of pancreatic pathology; the use of cellular markers of pancreatic function, inflammation, pain, and malignancy; and the refinement of methods to identify cells and cellular constituents of pancreatic cancer were discussed. The further refinement of sophisticated technical methods and the need for clinical studies to validate these new approaches in large-scale studies of patients at risk for the development of pancreatic disease were repeatedly emphasized.
C1 [Kelly, Kimberly A.] Univ Virginia, Dept Biomed Engn, Charlottesville, VA USA.
[Hollingsworth, Michael A.] Univ Nebraska, Sch Med, Eppley Canc Inst, Omaha, NE 68198 USA.
[Brand, Randall E.; Wasan, Ajay D.; Yadav, Dhiraj] Univ Pittsburgh, Sch Med, Dept Med, Div Gastroenterol Hepatol & Nutr, Pittsburgh, PA 15213 USA.
[Brand, Randall E.; Wasan, Ajay D.; Yadav, Dhiraj] Univ Pittsburgh, Sch Med, Dept Anesthesiol & Psychiat, Pittsburgh, PA USA.
[Liu, Christina H.] NCI, Off Canc Nanotechnol Res, NIH, Bethesda, MD 20892 USA.
[Liu, Christina H.] NCI, Canc Prevent Div, NIH, Bethesda, MD 20892 USA.
[Singh, Vikesh K.] Johns Hopkins Univ, Sch Med, Dept Med, Div Gastroenterol, Baltimore, MD 21205 USA.
[Srivastava, Sudhir] NCI, Canc Biomarkers Res Grp, Canc Prevent Div, NIH, Bethesda, MD 20892 USA.
[Andersen, Dana K.] Natl Inst Diabet & Digest & Kidney Dis, Div Digest Dis & Nutr, NIH, Bethesda, MD USA.
RP Kelly, KA (reprint author), Univ Virginia, Dept Biomed Engn, Robert M Berne Cardiovasc Res Ctr, 415 Lane Rd,Bldg MR5,Rm 1214, Charlottesville, VA 22904 USA.
EM kak3x@virginia.edu
FU National Pancreas Foundation
FX The authors and sponsors are grateful for the additional support of the
National Pancreas Foundation and for the on-site assistance of Ms Patter
Birsic, Mr Matthew Alsante, Ms Jessica Kruse, and Mr Dan Spracklen of
the National Pancreas Foundation and for the assistance of Ms Joy Merusi
of the University of Pittsburgh.
NR 1
TC 4
Z9 4
U1 3
U2 7
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0885-3177
EI 1536-4828
J9 PANCREAS
JI Pancreas
PD NOV
PY 2015
VL 44
IS 8
BP 1185
EP 1194
DI 10.1097/MPA.0000000000000552
PG 10
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA CU2AQ
UT WOS:000363324000006
PM 26465948
ER
PT J
AU Lee, L
Ito, T
Igarashi, H
Kawabe, K
Oda, Y
Jensen, RT
AF Lee, L.
Ito, T.
Igarashi, H.
Kawabe, K.
Oda, Y.
Jensen, R. T.
TI Long-Term Outcomes and Prognostic Factors in 78 Japanese Patients With
Advanced Pancreatic Neuroendocrine Tumors: A Single-Center Retrospective
Study
SO PANCREAS
LA English
DT Meeting Abstract
C1 [Lee, L.; Ito, T.; Igarashi, H.; Kawabe, K.] Kyushu Univ, Grad Sch Med Sci, Dept Med & Bioregulatory Sci, Fukuoka 812, Japan.
[Oda, Y.] Kyushu Univ, Grad Sch Med Sci, Dept Anat Pathol, Fukuoka 812, Japan.
[Jensen, R. T.] Natl Inst Diabet Digest & Kidney Dis, Digest Dis Branch, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0885-3177
EI 1536-4828
J9 PANCREAS
JI Pancreas
PD NOV
PY 2015
VL 44
IS 8
BP 1391
EP 1391
PG 1
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA CU2AQ
UT WOS:000363324000162
ER
PT J
AU Yamaguchi, H
Dangol, G
Ghosh, B
Gutkind, JS
Maitra, A
AF Yamaguchi, H.
Dangol, G.
Ghosh, B.
Gutkind, J. S.
Maitra, A.
TI Induction of R201C Mutant Gas Facilitates Murine Pancreatic
Tumorigenesis in Cooperation With G12D Mutant Kras
SO PANCREAS
LA English
DT Meeting Abstract
C1 [Yamaguchi, H.; Dangol, G.; Ghosh, B.; Maitra, A.] Univ Texas MD Anderson Canc Ctr, Sheikh Ahmed Ctr Pancreat Canc Res, Houston, TX 77030 USA.
[Gutkind, J. S.] Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0885-3177
EI 1536-4828
J9 PANCREAS
JI Pancreas
PD NOV
PY 2015
VL 44
IS 8
BP 1427
EP 1427
PG 1
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA CU2AQ
UT WOS:000363324000309
ER
PT J
AU Gotea, V
Gartner, JJ
Qutob, N
Elnitski, L
Samuels, Y
AF Gotea, Valer
Gartner, Jared J.
Qutob, Nouar
Elnitski, Laura
Samuels, Yardena
TI The functional relevance of somatic synonymous mutations in melanoma and
other cancers
SO PIGMENT CELL & MELANOMA RESEARCH
LA English
DT Article
DE synonymous mutations; cancer; melanoma; gene splicing; miRNA regulation;
secondary structure; protein translation; protein folding
ID CONGENITAL MELANOCYTIC NEVI; CUTANEOUS MALIGNANT-MELANOMA; UV-RADIATION
EXPOSURE; BRAF MUTATION; SPITZ NEVI; BLUE NEVI; N-RAS; TUMOR
PROGRESSION; NRAS MUTATIONS; CONSTITUTIVE ACTIVATION
AB Recent technological advances in sequencing have flooded the field of cancer research with knowledge about somatic mutations for many different cancer types. Most cancer genomics studies focus on mutations that alter the amino acid sequence, ignoring the potential impact of synonymous mutations. However, accumulating experimental evidence has demonstrated clear consequences for gene function, leading to a widespread recognition of the functional role of synonymous mutations and their causal connection to various diseases. Here, we review the evidence supporting the direct impact of synonymous mutations on gene function via gene splicing; mRNA stability, folding, and translation; protein folding; and miRNA-based regulation of expression. These results highlight the functional contribution of synonymous mutations to oncogenesis and the need to further investigate their detection and prioritization for experimental assessment.
C1 [Gartner, Jared J.] NHGRI, Translat & Funct Genom Branch, NIH, Bethesda, MD 20892 USA.
[Gartner, Jared J.] NCI, Surg Branch, NIH, Bethesda, MD 20892 USA.
[Qutob, Nouar; Samuels, Yardena] Weizmann Inst Sci, Dept Mol Cell Biol, IL-76100 Rehovot, Israel.
RP Samuels, Y (reprint author), Weizmann Inst Sci, Dept Mol Cell Biol, IL-76100 Rehovot, Israel.
EM elnitski@mail.nih.gov; Yardena.samuels@weizmann.ac.il
OI Gotea, Valer/0000-0001-7857-3309
FU Intramural Research Programs of the National Human Genome Research
Institute; Israel Science Foundation [1604/13, 877/13]; ERC
[StG-335377]; Knell Family; Peter and Patricia Gruber Award; Gideon
Hamburger, Israel
FX We thank F. Supek and B. Lehner for providing relevant data from their
study (Supek et al., 2014). This work was supported by the Intramural
Research Programs of the National Human Genome Research Institute (VG,
LE). YS is supported by Israel Science Foundation grant numbers 1604/13
and 877/13 and by the ERC (StG-335377), the Knell Family, the Peter and
Patricia Gruber Award, and Gideon Hamburger, Israel.
NR 120
TC 4
Z9 4
U1 2
U2 10
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1755-1471
EI 1755-148X
J9 PIGM CELL MELANOMA R
JI Pigment Cell Melanoma Res.
PD NOV
PY 2015
VL 28
IS 6
BP 673
EP 684
DI 10.1111/pcmr.12413
PG 12
WC Oncology; Cell Biology; Dermatology
SC Oncology; Cell Biology; Dermatology
GA CU3DL
UT WOS:000363404000008
PM 26300548
ER
PT J
AU Markt, SC
Shui, IM
Unger, RH
Urun, Y
Berg, CD
Black, A
Brennan, P
Bueno-De-Mesquita, HB
Gapstur, SM
Giovannucci, E
Haiman, C
Henderson, B
Hoover, RN
Hunter, DJ
Key, TJ
Khaw, KT
Canzian, F
Larranga, N
Le Marchand, L
Ma, J
Naccarati, A
Siddiq, A
Stampfer, MJ
Stattin, P
Stevens, VL
Stram, DO
Tjonneland, A
Travis, RC
Trichopoulos, D
Ziegler, RG
Lindstrom, S
Kraft, P
Mucci, LA
Choueiri, TK
Wilson, KM
AF Markt, Sarah C.
Shui, Irene M.
Unger, Robert H.
Urun, Yuksel
Berg, Christine D.
Black, Amanda
Brennan, Paul
Bueno-de-Mesquita, H. Bas
Gapstur, Susan M.
Giovannucci, Edward
Haiman, Christopher
Henderson, Brian
Hoover, Robert N.
Hunter, David J.
Key, Timothy J.
Khaw, Kay-Tee
Canzian, Federico
Larranga, Nerea
Le Marchand, Loic
Ma, Jing
Naccarati, Alessio
Siddiq, Afshan
Stampfer, Meir J.
Stattin, Par
Stevens, Victoria L.
Stram, Daniel O.
Tjonneland, Anne
Travis, Ruth C.
Trichopoulos, Dimitrios
Ziegler, Regina G.
Lindstrom, Sara
Kraft, Peter
Mucci, Lorelei A.
Choueiri, Toni K.
Wilson, Kathryn M.
TI ABO Blood Group Alleles and Prostate Cancer Risk: Results from the
Breast and Prostate Cancer Cohort Consortium (BPC3)
SO PROSTATE
LA English
DT Article
DE ABO; blood type; prostate cancer; genetic epidemiology
ID ASSOCIATION
AB BACKGROUND. ABO blood group has been associated with risk of cancers of the pancreas, stomach, ovary, kidney, and skin, but has not been evaluated in relation to risk of aggressive prostate cancer.
METHODS. We used three single nucleotide polymorphisms (SNPs) (rs8176746, rs505922, and rs8176704) to determine ABO genotype in 2,774 aggressive prostate cancer cases and 4,443 controls from the Breast and Prostate Cancer Cohort Consortium (BPC3). Unconditional logistic regression was used to calculate age and study-adjusted odds ratios and 95% confidence intervals for the association between blood type, genotype, and risk of aggressive prostate cancer (Gleason score >= 8 or locally advanced/metastatic disease (stage T3/T4/N1/M1).
RESULTS. We found no association between ABO blood type and risk of aggressive prostate cancer (Type A: OR = 0.97, 95% CI = 0.87-1.08; Type B: OR = 0.92, 95% CI = n0.77-1.09; Type AB: OR = 1.25, 95% CI = 0.98-1.59, compared to Type O, respectively). Similarly, there was no association between "dose" of A or B alleles and aggressive prostate cancer risk.
CONCLUSIONS. ABO blood type was not associated with risk of aggressive prostate cancer. Prostate 75: 1677-1681, 2015. (C) 2015 Wiley Periodicals, Inc.
C1 [Markt, Sarah C.; Shui, Irene M.; Unger, Robert H.; Giovannucci, Edward; Hunter, David J.; Ma, Jing; Stampfer, Meir J.; Trichopoulos, Dimitrios; Lindstrom, Sara; Kraft, Peter; Mucci, Lorelei A.; Wilson, Kathryn M.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Shui, Irene M.; Hunter, David J.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA.
[Urun, Yuksel] Ankara Univ, Fac Med, Dept Med Oncol, TR-06100 Ankara, Turkey.
[Berg, Christine D.] Johns Hopkins Med, Dept Radiat Oncol, Baltimore, MD USA.
[Black, Amanda] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Brennan, Paul; Hoover, Robert N.; Ziegler, Regina G.] Int Agcy Res Canc, F-69372 Lyon, France.
[Bueno-de-Mesquita, H. Bas] Natl Inst Publ Hlth & Environm RIVM, Bilthoven, Netherlands.
[Bueno-de-Mesquita, H. Bas] Univ Med Ctr, Dept Gastroenterol, Utrecht, Netherlands.
[Bueno-de-Mesquita, H. Bas] Univ Med Ctr, Dept Hepatol, Utrecht, Netherlands.
[Bueno-de-Mesquita, H. Bas] Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol, London, England.
[Bueno-de-Mesquita, H. Bas] Univ London Imperial Coll Sci Technol & Med, Dept Biostat, London, England.
[Bueno-de-Mesquita, H. Bas] Univ Malaya, Fac Med, Dept Social, Kuala Lumpur, Malaysia.
[Bueno-de-Mesquita, H. Bas] Univ Malaya, Fac Med, Dept Prevent Med, Kuala Lumpur, Malaysia.
[Gapstur, Susan M.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA.
[Giovannucci, Edward; Stevens, Victoria L.] Harvard Univ, TH Chan Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Haiman, Christopher; Henderson, Brian; Stram, Daniel O.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA.
[Hunter, David J.; Lindstrom, Sara; Kraft, Peter] Harvard Univ, TH Chan Sch Publ Hlth, Program Genet Epidemiol & Stat Genet, Boston, MA 02115 USA.
[Key, Timothy J.; Travis, Ruth C.] Univ Oxford, Nuffield Dept Populat Hlth, Canc Epidemiol Unit, Oxford, England.
[Khaw, Kay-Tee] Univ Cambridge, Cambridge Inst Publ Hlth, Sch Clin Med, Cambridge, England.
[Canzian, Federico] German Canc Res Ctr, Genom Epidemiol Grp, Heidelberg, Germany.
[Larranga, Nerea] BIODonostia Res Inst, Basque Hlth Dept, Publ Hlth Div Gipuzkoa, San Sebastian, Spain.
[Larranga, Nerea] CIBER Epidemiol & Publ Hlth CIBERESP, Madrid, Spain.
[Le Marchand, Loic] Univ Hawaii, Ctr Canc, Epidemiol Program, Honolulu, HI 96822 USA.
[Ma, Jing; Stampfer, Meir J.; Mucci, Lorelei A.] Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA.
[Ma, Jing; Stampfer, Meir J.; Mucci, Lorelei A.] Harvard Univ, Sch Med, Boston, MA USA.
[Naccarati, Alessio] HuGeF Fdn, Mol & Genet Epidemiol Unit, Turin, Italy.
[Siddiq, Afshan] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Genom Common Dis, London, England.
[Stattin, Par] Umea Univ, Dept Surg & Perioperat Sci, Urol & Androl, S-90187 Umea, Sweden.
[Tjonneland, Anne] Danish Canc Soc Res Ctr, Copenhagen, Denmark.
[Trichopoulos, Dimitrios] Acad Athens, Bureau Epidemiol Res, Athens, Greece.
[Trichopoulos, Dimitrios] Hellenic Hlth Fdn, Athens, Greece.
[Choueiri, Toni K.] Dana Farber Canc Inst, Dept Genitourinary Oncol, Boston, MA 02115 USA.
RP Markt, SC (reprint author), Harvard Univ, TH Chan Sch Publ Hlth, Dept Epidemiol, 677 Huntington Ave Room 920A, Boston, MA 02115 USA.
EM sec110@mail.harvard.edu
FU US National Institutes of Health, National Cancer Institute
[U01-CA98233, U01-CA98710, U01-CA98216, U01-CA98758, R01 CA63464, P01
CA33619, R37 CA54281, UM1 CA164973]; Intramural Research Program of the
Division of Cancer Epidemiology and Cancer Prevention (PLCO); Intramural
Research Program of the Division of Cancer Epidemiology and Cancer
Prevention (ATBC); Division of Cancer Epidemiology and Genetics; Danish
Cancer (Danish study Diet, Cancer and Health); Cancer Research EPIC
study of vitamin D and prostate cancer and the EPIC-UK cohorts; Medical
Research Council (EPIC study of vitamin D and prostate cancer and the
EPIC-UK cohorts); (EPIC-Greece) Foundation; Health Research Fund
(EPIC-Spain); Regional Government of Andalucia [6236]; Regional
Government of Asturias [6236]; Regional Government of Basque Country
[6236]; Regional Government of Murcia [6236]; Navarra (EPIC-Spain);
ISCIII (EPIC-Spain) [RD06/0020]; Sicilian government, Aire-Onlus Ragusa
(Italy)(EPIC-Italy); European Commission (MORGEN-EPIC); International
Agency for Research on (MORGEN-EPIC); Dutch Ministry of Public
(MORGEN-EPIC); Welfare and Sports (MORGEN-EPIC); Statistics
(MORGEN-EPIC); National Cancer Institute at the National Institutes of
Health Training Grant; U.S. Army Department of Defense Prostate Cancer
Post-doctoral Fellowship; Prostate Cancer Foundation Young Investigators
FX Grant sponsor: US National Institutes of Health, National Cancer
Institute; Grant numbers: U01-CA98233 (PHS, HPFS); U01-CA98710 (CPS2);
U01-CA98216 (EPIC); U01-CA98758; R01 CA63464; P01 CA33619; R37 CA54281;
UM1 CA164973 (MEC); Grant sponsor: Intramural Research Program of the
Division of Cancer Epidemiology and Cancer Prevention (PLCO and ATBC);
Grant sponsor: Division of Cancer Epidemiology and Genetics; Grant
sponsor: Danish Cancer (Danish study Diet, Cancer and Health); Grant
sponsor: Cancer Research EPIC study of vitamin D and prostate cancer and
the EPIC-UK cohorts; Grant sponsor: Medical Research Council (EPIC study
of vitamin D and prostate cancer and the EPIC-UK cohorts); Grant
sponsor: (EPIC-Greece) Foundation; Grant sponsor: Health Research Fund
(EPIC-Spain); Grant sponsor: Regional Governments of Andalucia,
Asturias, Basque Country, Murcia (No. 6236) and Navarra (EPIC-Spain);
Grant sponsor: ISCIII (EPIC-Spain); Grant number: RD06/0020; Grant
sponsor: Sicilian government, Aire-Onlus Ragusa (Italy)(EPIC-Italy);
Grant sponsor: European Commission (MORGEN-EPIC); Grant sponsor:
International Agency for Research on (MORGEN-EPIC); Grant sponsor: Dutch
Ministry of Public (MORGEN-EPIC); Grant sponsor: Welfare and Sports
(MORGEN-EPIC); Grant sponsor: Statistics (MORGEN-EPIC); Grant sponsor:
National Cancer Institute at the National Institutes of Health Training
Grant; Grant number: (to SCM); Grant sponsor: U.S. Army Department of
Defense Prostate Cancer Post-doctoral Fellowship; Grant number: (to
IMS); Grant sponsor: Prostate Cancer Foundation Young Investigators;
Grant number: (to LAM and KMW).
NR 8
TC 0
Z9 0
U1 1
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0270-4137
EI 1097-0045
J9 PROSTATE
JI Prostate
PD NOV 1
PY 2015
VL 75
IS 15
BP 1677
EP 1681
DI 10.1002/pros.23035
PG 5
WC Endocrinology & Metabolism; Urology & Nephrology
SC Endocrinology & Metabolism; Urology & Nephrology
GA CU0PJ
UT WOS:000363219200001
PM 26268879
ER
PT J
AU Barry, KH
Moore, LE
Liao, LM
Huang, WY
Andreotti, G
Poulin, M
Berndt, SI
AF Barry, Kathryn Hughes
Moore, Lee E.
Liao, Linda M.
Huang, Wen-Yi
Andreotti, Gabriella
Poulin, Matthew
Berndt, Sonja I.
TI Prospective Study of DNA Methylation at LINE-1 and Alu in Peripheral
Blood and the Risk of Prostate Cancer
SO PROSTATE
LA English
DT Article
DE global DNA methylation; pre-diagnostic; prostate cancer; repetitive
element
ID BREAST-CANCER; LEUKOCYTE DNA; REPETITIVE ELEMENT; BLADDER-CANCER; CELL
CARCINOMA; HYPOMETHYLATION; ASSOCIATION; TUMOR; HYPERMETHYLATION;
POPULATION
AB BACKGROUND. Evidence suggests that global blood DNA methylation levels may be associated with the risk of various cancers, but no studies have evaluated this relationship for prostate cancer.
METHODS. We used pyrosequencing to quantify DNA methylation levels at the long interspersed nuclear element 1 (LINE-1) and Alu repetitive elements in pre-diagnostic blood samples from 694 prostate cancer cases and 703 controls from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. We evaluated prostate cancer risk associated with the mean methylation level for each element using logistic regression, adjusting for potential confounders.
RESULTS. We did not observe a significant association with prostate cancer for LINE-1 [ odds ratio (OR) for the highest compared to the lowest quartile = 1.01, 95% confidence interval (CI): 0.73-1.39, P-trend = 0.99] or Alu (OR = 0.94, 95% CI: 0.68-1.29, P-trend = 0.69) methylation levels overall. However, for Alu, we observed that higher DNA methylation levels were associated with a significant increased risk for those diagnosed 4 or more years after blood draw (OR = 2.26, 95% CI: 1.27-4.00, P-trend = 4.4 x 10(-3)). In contrast, there was no association for those diagnosed 2 (OR = 1.13, 95% CI: 0.67-1.90, P-trend = 0.64) or 3 years after draw (OR = 1.22, 95% CI: 0.71-2.07, P-trend = 0.32), and a decreased risk for those diagnosed less than 2 years after draw (OR = 0.40, 95% CI: 0.25-0.65, P-trend = 3.8 x 10(-5); P-heterogeneity = 5.3 x 10(-6)).
CONCLUSIONS. Although LINE-1 DNA methylation levels were not associated with prostate cancer, we observed an association for Alu that varied by time from blood draw to diagnosis. Our study suggests that elevated Alu blood DNA methylation levels several years before diagnosis may be associated with an increased prostate cancer risk. (C) 2015 Wiley Periodicals, Inc.
C1 [Barry, Kathryn Hughes; Moore, Lee E.; Huang, Wen-Yi; Andreotti, Gabriella; Berndt, Sonja I.] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Liao, Linda M.] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Poulin, Matthew] EpigenDx Inc, Hopkinton, MA USA.
RP Barry, KH (reprint author), NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, 9609 Med Ctr Dr,Rm 6E116 MSC 9771, Bethesda, MD 20892 USA.
EM barrykh@mail.nih.gov
OI Liao, Linda/0000-0002-1923-5294
FU Intramural Research Program of the National Cancer Institute, National
Institutes of Health
FX Grant sponsor: Intramural Research Program of the National Cancer
Institute, National Institutes of Health.
NR 26
TC 9
Z9 9
U1 0
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0270-4137
EI 1097-0045
J9 PROSTATE
JI Prostate
PD NOV 1
PY 2015
VL 75
IS 15
BP 1718
EP 1725
DI 10.1002/pros.23053
PG 8
WC Endocrinology & Metabolism; Urology & Nephrology
SC Endocrinology & Metabolism; Urology & Nephrology
GA CU0PJ
UT WOS:000363219200005
PM 26250474
ER
PT J
AU Fang, MZ
Ohman-Strickland, P
Kelly-McNeil, K
Kipen, H
Crabtree, BF
Lew, JP
Zarbl, H
AF Fang, Ming Zhu
Ohman-Strickland, Pamela
Kelly-McNeil, Kathie
Kipen, Howard
Crabtree, Benjamin F.
Lew, Jenny Pan
Zarbl, Helmut
TI Sleep interruption associated with house staff work schedules alters
circadian gene expression
SO SLEEP MEDICINE
LA English
DT Article
DE Circadian rhythm; Biomarker; Shift worker; PERIOD 2; Breast cancer
ID NIGHT-SHIFT WORK; CANCER PREVENTION TRIAL; BREAST-CANCER; VITAMIN-E;
URINARY MELATONIN; PROSTATE-CANCER; CLOCK; RISK; DISRUPTION; NURSES
AB Background: Epidemiological studies indicate that disruption of circadian rhythm by shift work increases the risk of breast and prostate cancer. Our studies demonstrated that carcinogens disrupt the circadian expression of circadian genes (CGs) and circadian-controlled genes (CCGs) during the early stages of rat mammary carcinogenesis. A chemopreventive regimen of methylselenocysteine (MSC) restored the circadian expression of CGs and CCGs, including PERIOD 2 (PER2) and estrogen receptor beta (ERS2), to normal. The present study evaluated whether changes in CG and CCG expression in whole blood can serve as indicators of circadian disruption in shift workers.
Methods: Fifteen shift workers were recruited to a crossover study. Blood samples were drawn before (6 PM) and after (8 AM) completing a night shift after at least seven days on floating night-shift rotation, and before (8 AM), during (1 PM), and after (6 PM) completing seven days on day shift. The plasma melatonin level and messenger RNA (mRNA) expression of PER2, nuclear receptor subfamily 1, group d, member 1 (NR1D1), and ERS2 were measured, and the changes in levels of melatonin and gene expression were evaluated with statistical analyses.
Results: The mRNA expression of PER2 was affected by shift (p = 0.0079); the levels were higher in the evening for the night shift, but higher in the morning for the day shift. Increased PER2 expression (p = 0.034) was observed in the evening on the night versus day shifts. The melatonin level was higher in the morning for both day shifts (p = 0.013) and night shifts (p < 0.0001).
Conclusion: Changes in the level of PER2 gene expression can serve as a biomarker of disrupted circadian rhythm in blood cells. Therefore, they can be a useful intermediate indicator of efficacy in future MSC-mediated chemoprevention studies. (C) 2015 Elsevier B.V. All rights reserved.
C1 [Fang, Ming Zhu; Kelly-McNeil, Kathie; Kipen, Howard; Zarbl, Helmut] Robert Wood Johnson Med Sch, Dept Environm & Occupat Med, Piscataway, NJ USA.
[Fang, Ming Zhu; Ohman-Strickland, Pamela; Kelly-McNeil, Kathie; Kipen, Howard; Zarbl, Helmut] NIEHS, Ctr Environm Exposures & Dis, Environm & Occupat Hlth Sci Inst, Piscataway, NJ USA.
[Fang, Ming Zhu; Crabtree, Benjamin F.; Zarbl, Helmut] Rutgers State Univ, Canc Inst New Jersey, Piscataway, NJ 08854 USA.
[Ohman-Strickland, Pamela] Sch Publ Hlth, Dept Biostat, Piscataway, NJ USA.
[Crabtree, Benjamin F.] Robert Wood Johnson Med Sch, Family Med, Piscataway, NJ USA.
[Lew, Jenny Pan] Childrens Natl Med Ctr, Washington, DC 20010 USA.
RP Zarbl, H (reprint author), Rutgers State Univ, Robert Wood Johnson Med Sch, Environm & Occupat Hlth Sci Inst, 170 Frelinghuysen Rd, Piscataway, NJ 08854 USA.
EM zarbl@eohsi.rutgers.edu
FU V Foundation for Cancer Research; National Institute of Environmental
Health Sciences (NIEHS) [P30ES005022]; Environmental and Occupational
Health Sciences Institute at Rutgers, The State University of New Jersey
FX These studies were supported by a Translational Research Grant from the
V Foundation for Cancer Research (H. Zarbl), an environmental health
sciences center grant (P30ES005022) from the National Institute of
Environmental Health Sciences (NIEHS) (H. Zarbl), and the Environmental
and Occupational Health Sciences Institute at Rutgers, The State
University of New Jersey (H. Zarbl). The authors thank the house staff
in the departments of family medicine and pediatrics at Robert Wood
Johnson University Hospital and the Clinical Research Center staff of
Robert Wood Johnson Medical School, at Rutgers University.
NR 37
TC 3
Z9 3
U1 2
U2 9
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1389-9457
EI 1878-5506
J9 SLEEP MED
JI Sleep Med.
PD NOV
PY 2015
VL 16
IS 11
BP 1388
EP 1394
DI 10.1016/j.sleep.2015.06.011
PG 7
WC Clinical Neurology
SC Neurosciences & Neurology
GA CU4CL
UT WOS:000363473700014
PM 26498241
ER
PT J
AU Hasin, DS
Grant, BF
AF Hasin, Deborah S.
Grant, Bridget F.
TI The National Epidemiologic Survey on Alcohol and Related Conditions
(NESARC) Waves 1 and 2: review and summary of findings
SO SOCIAL PSYCHIATRY AND PSYCHIATRIC EPIDEMIOLOGY
LA English
DT Review
DE Epidemiology; National survey; Alcohol and drugs; Mood disorders;
Comorbidity; Anxiety disorders; Personality disorders
ID SUBSTANCE-USE DISORDERS; DSM-IV ALCOHOL; DRUG-USE DISORDERS; MAJOR
DEPRESSIVE DISORDER; POSTTRAUMATIC-STRESS-DISORDER; GENERAL-POPULATION
SAMPLE; SOCIAL ANXIETY DISORDER; CANNABIS USE DISORDERS; BORDERLINE
PERSONALITY-DISORDER; ANTISOCIAL BEHAVIORAL SYNDROMES
AB The NESARC, a "third-generation" psychiatric epidemiologic survey that integrated detailed measures of alcohol and drug use and problems has been the data source for over > 850 publications. A comprehensive review of NESARC findings and their implications is lacking.
NESARC was a survey of 43,093 participants that covered alcohol, drug and psychiatric disorders, risk factors, and consequences. Wave 1 of the NESARC was conducted in 2001-2002. Three years later, Wave 2 follow-up re-interviews were conducted with 34,653 of the original participants. Scopus and Pubmed were used to search for NESARC papers, which were sorted into topic areas and summarized.
The most common disorders were alcohol and posttraumatic stress disorders, and major depression. Females had more internalizing disorders and males had more externalizing disorders, although the preponderance of males with alcohol disorders (the "gender gap") was less pronounced than it was in previous decades. A race/ethnic "paradox" (lower risk among disadvantaged minorities than whites) remains unexplained. Younger participants had higher risk for substance and personality disorders, but not unipolar depressive or anxiety disorders. Psychiatric comorbidity was extensive and often formed latent trans-diagnostic domains. Since 1991-1992, risk for marijuana and prescription drug disorders increased, while smoking decreased, although smoking decreases were less pronounced among those with comorbidity. A nexus of comorbidity, social support, and stress predicted transitions in diagnostic status between Waves 1 and 2. Childhood maltreatment predicted psychopathology. Alcohol and drug use disorders were seldom treated; attitudinal barriers (little perceived need, perceived alcoholism stigma, pessimism about efficacy) were more important in predicting non-treatment than financial barriers.
Understanding comorbidity and the effects of early stressors will require research incorporating biologic components, e.g., genetic variants and brain imaging. The lack of treatment for alcohol and drug disorders, predicted by attitudinal rather than financial variables, suggests an urgent need for public and professional education to reduce the stigma associated with these disorders and increase knowledge of treatment options.
C1 [Hasin, Deborah S.] Coll Phys & Surg, Dept Psychiat, New York, NY 10032 USA.
[Hasin, Deborah S.] Columbia Univ, Mailman Sch Publ Hlth, New York, NY 10032 USA.
[Hasin, Deborah S.] New York State Psychiat Inst & Hosp, New York, NY 10032 USA.
[Grant, Bridget F.] NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH, Rockville, MD 20852 USA.
RP Grant, BF (reprint author), NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH, 5635 Fishers Lane,Room 3077, Rockville, MD 20852 USA.
EM bgrant@mail.nih.gov
FU National Institute on Alcohol Abuse and Alcoholism (NIAAA); National
Institute on Drug Abuse; NIAAA [U01AA018111]; Columbia University; New
York State Psychiatric Institute; NIAAA, NIH
FX The NESARC-III was sponsored by the National Institute on Alcohol Abuse
and Alcoholism (NIAAA), with supplemental support from the National
Institute on Drug Abuse. Support is acknowledged from NIAAA U01AA018111,
Columbia University, and New York State Psychiatric Institute (Hasin).
Support is also acknowledged from the intramural program, NIAAA, NIH. To
obtain the NESARC datasets, contact Aaron White at NIAAA,
whitea4@mail.nih.gov.
NR 548
TC 25
Z9 25
U1 28
U2 61
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 0933-7954
EI 1433-9285
J9 SOC PSYCH PSYCH EPID
JI Soc. Psychiatry Psychiatr. Epidemiol.
PD NOV
PY 2015
VL 50
IS 11
BP 1609
EP 1640
DI 10.1007/s00127-015-1088-0
PG 32
WC Psychiatry
SC Psychiatry
GA CU0ZY
UT WOS:000363249700001
PM 26210739
ER
PT J
AU Holmberg, C
Whitehouse, K
Daly, M
McCaskill-Stevens, W
AF Holmberg, Christine
Whitehouse, Katie
Daly, Mary
McCaskill-Stevens, Worta
TI Gaining control over breast cancer risk: Transforming vulnerability,
uncertainty, and the future through clinical trial participation - a
qualitative study
SO SOCIOLOGY OF HEALTH & ILLNESS
LA English
DT Article
DE breast cancer; randomised controlled trials (RCT); narrative method
ID SURGICAL ADJUVANT BREAST; PREVENTION TRIAL; BOWEL PROJECT; TAMOXIFEN;
PHARMACEUTICALIZATION; RECRUITMENT; RALOXIFENE; EXPERIENCE; DISEASE;
HEALTH
AB Concepts of disease risk and its management are central to processes of medicalisation and pharmaceuticalisation. Through a narrative perspective, this paper aims to understand how such macro-level developments may (or may not) be experienced individually, and how an algorithm that is used for recruitment into a clinical trial may structure individual notions of being at risk' and in need of treatment'. We interviewed 31 women participating in the Study of Tamoxifen and Raloxifene (STAR), a chemoprevention trial conducted in the US between 1999 and 2006. Interviews were thematically analysed. Women in the study had experienced the threat of breast cancer and felt vulnerable to developing the disease prior to STAR participation. The diagnosis of being at risk' for cancer through an algorithm that determined risk-eligibility for STAR, opened up the possibility for the women to heal. The trial became a means to recognise and collectivise the women's experiences of vulnerability. Through medication intake, being cared for by study coordinators, and the sense of community with other STAR participants, trial participation worked to transform women's lives. Such transformative experiences may nevertheless have been temporary, enduring only as long as the close links to the medical institution through trial participation lasted.
C1 [Holmberg, Christine; Whitehouse, Katie] Charite Univ Med Berlin, Berlin Sch Publ Hlth, Berlin, Germany.
[Daly, Mary] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA.
[McCaskill-Stevens, Worta] Natl Canc Inst, Div Canc Prevent, Bethesda, MD USA.
RP Holmberg, C (reprint author), Dept Social Med Epidemiol & Hlth Econ, Luisenstr 57, D-10098 Berlin, Germany.
EM christine.holmberg@charite.de
FU Intramural NIH HHS [Z99 CA999999]
NR 49
TC 1
Z9 1
U1 2
U2 12
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0141-9889
EI 1467-9566
J9 SOCIOL HEALTH ILL
JI Sociol. Health Ill.
PD NOV
PY 2015
VL 37
IS 8
BP 1373
EP 1387
DI 10.1111/1467-9566.12307
PG 15
WC Public, Environmental & Occupational Health; Social Sciences,
Biomedical; Sociology
SC Public, Environmental & Occupational Health; Biomedical Social Sciences;
Sociology
GA CU1ZK
UT WOS:000363320700016
PM 26235092
ER
PT J
AU Huang, YY
Kaneko, KJ
Pan, HY
DePamphilis, ML
AF Huang, Yi-Yuan
Kaneko, Kotaro J.
Pan, Haiyan
DePamphilis, Melvin L.
TI Geminin is Essential to Prevent DNA Re-Replication-Dependent Apoptosis
in Pluripotent Cells, but not in Differentiated Cells
SO STEM CELLS
LA English
DT Article
DE Geminin; DNA re-replication; Apoptosis; Pluripotent; Embryonic stem
cells; Embryonic fibroblasts
ID EMBRYONIC STEM-CELLS; DAMAGE-INDUCED PHOSPHORYLATION; MESENCHYMAL
TRANSITION; MAMMALIAN DEVELOPMENT; CELLULAR SENESCENCE; G(2)/M
CHECKPOINT; FATE ACQUISITION; GENE-EXPRESSION; GERM LAYERS; IN-VIVO
AB Geminin is a dual-function protein unique to multicellular animals with roles in modulating gene expression and preventing DNA re-replication. Here, we show that geminin is essential at the beginning of mammalian development to prevent DNA re-replication in pluripotent cells, exemplified by embryonic stem cells, as they undergo self-renewal and differentiation. Embryonic stem cells, embryonic fibroblasts, and immortalized fibroblasts were characterized before and after geminin was depleted either by gene ablation or siRNA. Depletion of geminin under conditions that promote either self-renewal or differentiation rapidly induced DNA re-replication, followed by DNA damage, then a DNA damage response, and finally apoptosis. Once differentiation had occurred, geminin was no longer essential for viability, although it continued to contribute to preventing DNA re-replication induced DNA damage. No relationship was detected between expression of geminin and genes associated with either pluripotency or differentiation. Thus, the primary role of geminin at the beginning of mammalian development is to prevent DNA re-replication-dependent apoptosis, a role previously believed essential only in cancer cells. These results suggest that regulation of gene expression by geminin occurs only after pluripotent cells differentiate into cells in which geminin is not essential for viability.
C1 [Huang, Yi-Yuan; Kaneko, Kotaro J.; Pan, Haiyan; DePamphilis, Melvin L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA.
RP DePamphilis, ML (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bldg 6A,Room 3A15,MSC 2753,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM de-pamphm@mail.nih.gov
FU Eunice Shriver Kennedy National Institute of Child Health and Human
Development (NICHD)
FX We thank Dr. Alex Vassilev for help with Flow Cytometry and Xiaohong
Zhang for maintaining our mouse colony. This work was supported by
Eunice Shriver Kennedy National Institute of Child Health and Human
Development (NICHD) intramural research program. K.J.K. is currently
affiliated with the Division of Biotechnology and GRAS Notice Review,
Center for Food Safety and Applied Nutrition, Food and Drug
Administration, College Park, Maryland.
NR 64
TC 4
Z9 4
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1066-5099
EI 1549-4918
J9 STEM CELLS
JI Stem Cells
PD NOV
PY 2015
VL 33
IS 11
BP 3239
EP 3253
DI 10.1002/stem.2092
PG 15
WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology;
Oncology; Cell Biology; Hematology
SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology
GA CU1FP
UT WOS:000363265900009
PM 26140583
ER
PT J
AU Wu, TT
Liu, Y
Fan, ZP
Xu, JJ
Jin, LY
Gao, ZH
Wu, ZF
Hu, L
Wang, JS
Zhang, CM
Chen, WJ
Wang, SL
AF Wu, Tingting
Liu, Yi
Fan, Zhipeng
Xu, Junji
Jin, Luyuan
Gao, Zhenhua
Wu, Zhifang
Hu, Lei
Wang, Jinsong
Zhang, Chunmei
Chen, Wanjun
Wang, Songlin
TI miR-21 Modulates the Immunoregulatory Function of Bone Marrow
Mesenchymal Stem Cells Through the PTEN/Akt/TGF-beta 1 Pathway
SO STEM CELLS
LA English
DT Article
DE miR-21; Immunoregulation; Mesenchymal stem cells; Transforming growth
factor-beta 1; PTEN
ID REGULATORY T-CELLS; TGF-BETA; NITRIC-OXIDE; CANCER; DIFFERENTIATION;
PROLIFERATION; INDUCTION; MICRORNAS; MIR-146; GROWTH
AB microRNAs (miRNAs) act as regulatory signals for maintaining stemness, self-renewal, and differentiation of mesenchymal stem cells (MSCs), but whether miRNAs modulate the immunoregulatory function of MSCs remains largely unknown. Here, we show that miR-21 negatively regulates the activity of immunoregulatory cytokine transforming growth factor-beta 1 (TGF-beta 1) in MSCs. Consistently, bone marrow MSCs (BMMSCs) from miR-21(-/-) mice show enhanced immunosuppressive function by more TGF-beta 1 secretion and induce more CD4(+)Foxp3(+) regulatory T cells compared with wild-type BMMSCs in vitro, which anti-TGF-beta 1 antibody abrogates. Mechanistically, miR-21 inhibits TGF-beta 1 expression by targeting phosphatase and tensin homolog deleted on chromosome 10 (PTEN) in BMMSCs. Downstream of PTEN, miR-21 promotes activation of Akt, and consequently increases activation of NF-kappa B pathway. Importantly, adoptive transfer of miR-21(-/-) BMMSCs into mice with experimental colitis more effectively ameliorates colonic inflammation in a TGF-beta 1-dependent manner. Thus, these findings indicate a previously uncovered mechanism of miR-21 control immunoregulatory function of BMMSCs through TGF-beta 1 inhibition.
C1 [Wu, Tingting; Xu, Junji; Jin, Luyuan; Gao, Zhenhua; Wu, Zhifang; Hu, Lei; Wang, Jinsong; Zhang, Chunmei; Wang, Songlin] Capital Med Univ, Sch Stomatol, Mol Lab Gene Therapy & Tooth Regenerat, Beijing 100050, Peoples R China.
[Liu, Yi] Capital Med Univ, Sch Stomatol, Lab Tissue Regenerat & Immunol, Beijing 100050, Peoples R China.
[Liu, Yi] Capital Med Univ, Sch Stomatol, Dept Periodont, Beijing 100050, Peoples R China.
[Fan, Zhipeng] Capital Med Univ, Sch Stomatol, Lab Mol Signaling & Stem Cell Therapy, Beijing Key Lab Tooth Regenerat & Funct Reconstru, Beijing 100050, Peoples R China.
[Chen, Wanjun] Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA.
[Wang, Songlin] Capital Med Univ, Sch Basic Med Sci, Dept Biochem & Mol Biol, Beijing 100050, Peoples R China.
RP Wang, SL (reprint author), Capital Med Univ, Mol Lab Gene Therapy & Tooth Regenerat, Beijing Key Lab Tooth Regenerat & Funct Reconstru, Sch Stomatol, Beijing 100050, Peoples R China.
EM slwang@ccmu.edu.cn
FU Beijing Municipality Government [PXM2014_014226_000180,
PXM2014_014226_000048, PXM2014_014226_000013, PXM2014_014226_000053,
Z121100005212004, PXM 2013_014226_000021, PXM 2013_014226_07_000080,
TJSHG201310025005]; National Basic Research Program of China
[2010CB944801]; National Natural Science Foundation of China
[NSFC81222011, 81470751]; NIH, NIDCR
FX This work was supported by the Beijing Municipality Government Grants
(Beijing Scholar Program-PXM2014_014226_000180, PXM2014_014226_000048,
PXM2014_014226_000013, PXM2014_014226_000053, Z121100005212004, PXM
2013_014226_000021, PXM 2013_014226_07_000080, and TJSHG201310025005 [to
S.W.]), the National Basic Research Program of China (2010CB944801 [to
S.W.]), National Natural Science Foundation of China (NSFC81222011,
81470751 [to Y.L.]), and the Intramural Research Program of NIH, NIDCR
(to W.C.).
NR 37
TC 8
Z9 8
U1 3
U2 15
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1066-5099
EI 1549-4918
J9 STEM CELLS
JI Stem Cells
PD NOV
PY 2015
VL 33
IS 11
BP 3281
EP 3290
DI 10.1002/stem.2081
PG 10
WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology;
Oncology; Cell Biology; Hematology
SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology
GA CU1FP
UT WOS:000363265900012
PM 26086742
ER
PT J
AU Marcus, PM
Freedman, AN
Khoury, MJ
AF Marcus, Pamela M.
Freedman, Andrew N.
Khoury, Muin J.
TI Targeted Cancer Screening in Average-Risk Individuals
SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE
LA English
DT Article
ID SERVICES TASK-FORCE; COLORECTAL-CANCER; PROSTATE-CANCER; LUNG-CANCER;
RECOMMENDATION STATEMENT; NEGATIVE COLONOSCOPY; AMERICAN-COLLEGE;
GUIDELINES; SUSCEPTIBILITY; STRATEGIES
AB Targeted cancer screening refers to use of disease risk information to identify those most likely to benefit from screening. Researchers have begun to explore the possibility of refining screening regimens for average-risk individuals' using genetic and non-genetic risk factors and previous screening experience. Average-risk individuals are those not known to be at substantially elevated risk, including those without known inherited predisposition, without comorbidities known to increase cancer risk, and without previous diagnosis of cancer or pre-cancer. In this paper, we describe the goals of targeted cancer screening in average-risk individuals, present factors on which cancer screening has been targeted, discuss inclusion of targeting in screening guidelines issued by major U.S. professional organizations, and present evidence to support or question such inclusion. Screening guidelines for average-risk individuals currently target age; smoking (lung cancer only); and, in some instances, race; family history of cancer; and previous negative screening history (cervical cancer only). No guidelines include common genomic polymorphisms. RCTs suggest that targeting certain ages and smoking histories reduces disease-specific cancer mortality, although some guidelines extend ages and smoking histories based on statistical modeling. Guidelines that are based on modestly elevated disease risk typically have either no or little evidence of an ability to affect a mortality benefit. In time, targeted cancer screening is likely to include genetic factors and past screening experience as well as non-genetic factors other than age, smoking, and race, but it is of utmost importance that clinical implementation be evidence-based. Published by Elsevier Inc. on behalf of American Journal of Preventive Medicine
C1 [Marcus, Pamela M.; Freedman, Andrew N.; Khoury, Muin J.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
RP Marcus, PM (reprint author), NCI, Div Canc Control & Populat Sci, 9609 Med Ctr Dr,Room 4E608, Bethesda, MD 20892 USA.
EM marcusp@mail.nih.gov
FU Intramural NIH HHS [Z99 CA999999]
NR 37
TC 3
Z9 3
U1 1
U2 5
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0749-3797
EI 1873-2607
J9 AM J PREV MED
JI Am. J. Prev. Med.
PD NOV
PY 2015
VL 49
IS 5
BP 765
EP 771
DI 10.1016/j.amepre.2015.04.030
PG 7
WC Public, Environmental & Occupational Health; Medicine, General &
Internal
SC Public, Environmental & Occupational Health; General & Internal Medicine
GA CT7MK
UT WOS:000362998600014
PM 26165196
ER
PT J
AU Basile, BM
Moylan, EJ
Charles, DP
Murray, EA
AF Basile, Benjamin M.
Moylan, Emily J.
Charles, David P.
Murray, Elisabeth A.
TI Two-item same/different discrimination in rhesus monkeys (Macaca
mulatta)
SO ANIMAL COGNITION
LA English
DT Article
DE Categorization; Concept learning; Entropy; Perceptual variability
ID SAME-DIFFERENT DISCRIMINATION; VARIABILITY DISCRIMINATION; FINDING
DIFFERENCES; VISUAL-DISPLAYS; PIGEONS; AMYGDALA; LESIONS; BIRDS
AB Almost all nonhuman animals can recognize when one item is the same as another item. It is less clear whether nonhuman animals possess abstract concepts of "same" and "different" that can be divorced from perceptual similarity. Pigeons and monkeys show inconsistent performance, and often surprising difficulty, in laboratory tests of same/different learning that involve only two items. Previous results from tests using multi-item arrays suggest that nonhumans compute sameness along a continuous scale of perceptual variability, which would explain the difficulty of making two-item same/different judgments. Here, we provide evidence that rhesus monkeys can learn a two-item same/different discrimination similar to those on which monkeys and pigeons have previously failed. Monkeys' performance transferred to novel stimuli and was not affected by perceptual variations in stimulus size, rotation, view, or luminance. Success without the use of multi-item arrays, and the lack of effect of perceptual variability, suggests a computation of sameness that is more categorical, and perhaps more abstract, than previously thought.
C1 [Basile, Benjamin M.; Moylan, Emily J.; Charles, David P.; Murray, Elisabeth A.] NIMH, Sect Neurobiol Learning & Memory, Neuropsychol Lab, NIH, Bethesda, MD 20892 USA.
RP Basile, BM (reprint author), NIMH, Sect Neurobiol Learning & Memory, Neuropsychol Lab, NIH, Bldg 49,Room 1B80,49 Convent Dr MSC 4415, Bethesda, MD 20892 USA.
EM benjamin.basile@nih.gov
FU Intramural Research Program of the National Institute of Mental Health
FX David P. Charles passed away on October 17, 2006. We thank Luke Humphrey
for help testing monkeys. We thank an anonymous reviewer for suggesting
an additional analysis. This work was supported by the Intramural
Research Program of the National Institute of Mental Health. The authors
declare that they have no conflict of interest. All procedures were
reviewed and approved by the NIMH Animal Care and Use Committee and
complied with US law.
NR 31
TC 1
Z9 1
U1 6
U2 11
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 1435-9448
EI 1435-9456
J9 ANIM COGN
JI Anim. Cogn.
PD NOV
PY 2015
VL 18
IS 6
BP 1221
EP 1230
DI 10.1007/s10071-015-0891-z
PG 10
WC Behavioral Sciences; Zoology
SC Behavioral Sciences; Zoology
GA CT6YS
UT WOS:000362960200003
PM 26142053
ER
PT J
AU Krishnan, S
Dhillon, PK
Bhadelia, A
Schurmann, A
Basu, P
Bhatla, N
Birur, P
Colaco, R
Dey, S
Grover, S
Gupta, H
Gupta, R
Gupta, V
Lewis, MA
Mehrotra, R
McMikel, A
Mukherji, A
Naik, N
Nyblade, L
Pati, S
Pillai, MR
Rajaraman, P
Ramesh, C
Rath, GK
Reithinger, R
Sankaranarayanan, R
Selvam, J
Shanmugam, MS
Shridhar, K
Siddiqi, M
Squiers, L
Subramanian, S
Travasso, SM
Verma, Y
Vijayakumar, M
Weiner, BJ
Reddy, KS
Knaul, FM
AF Krishnan, Suneeta
Dhillon, Preet K.
Bhadelia, Afsan
Schurmann, Anna
Basu, Partha
Bhatla, Neerja
Birur, Praveen
Colaco, Rajeev
Dey, Subhojit
Grover, Surbhi
Gupta, Harmala
Gupta, Rakesh
Gupta, Vandana
Lewis, Megan A.
Mehrotra, Ravi
McMikel, Ann
Mukherji, Arnab
Naik, Navami
Nyblade, Laura
Pati, Sanghamitra
Pillai, M. Radhakrishna
Rajaraman, Preetha
Ramesh, Chalurvarayaswamy
Rath, G. K.
Reithinger, Richard
Sankaranarayanan, Rengaswamy
Selvam, Jerard
Shanmugam, M. S.
Shridhar, Krithiga
Siddiqi, Maqsood
Squiers, Linda
Subramanian, Sujha
Travasso, Sandra M.
Verma, Yogesh
Vijayakumar, M.
Weiner, Bryan J.
Reddy, K. Srinath
Knaul, Felicia M.
TI Report from a symposium on catalyzing primary and secondary prevention
of cancer in India
SO CANCER CAUSES & CONTROL
LA English
DT Article
DE Cancer; Prevention; Policy; Advocacy; India; Symposium
ID PRIMARY-HEALTH-CARE; CERVICAL-CANCER; HUMAN-PAPILLOMAVIRUS; RESOURCE
COUNTRIES; RANDOMIZED-TRIAL; INCOME COUNTRIES; ORAL-CANCER; BREAST;
BURDEN; MEXICO
AB Oral, breast, and cervical cancers are amenable to early detection and account for a third of India's cancer burden. We convened a symposium of diverse stakeholders to identify gaps in evidence, policy, and advocacy for the primary and secondary prevention of these cancers and recommendations to accelerate these efforts.
Indian and global experts from government, academia, private sector (health care, media), donor organizations, and civil society (including cancer survivors and patient advocates) presented and discussed challenges and solutions related to strategic communication and implementation of prevention, early detection, and treatment linkages.
Innovative approaches to implementing and scaling up primary and secondary prevention were discussed using examples from India and elsewhere in the world. Participants also reflected on existing global guidelines and national cancer prevention policies and experiences.
Symposium participants proposed implementation-focused research, advocacy, and policy/program priorities to strengthen primary and secondary prevention efforts in India to address the burden of oral, breast, and cervical cancers and improve survival.
C1 [Krishnan, Suneeta] Res Triangle Inst Global India Pvt Ltd, Paharpur Business Ctr, New Delhi 110019, India.
[Dhillon, Preet K.; Shridhar, Krithiga] Publ Hlth Fdn India, Ctr Chron Condit & Injuries, Sect 44, Gurgaon 122002, India.
[Bhadelia, Afsan; Knaul, Felicia M.] Harvard Univ, Harvard Global Equity Initiat, Boston, MA 02115 USA.
[Schurmann, Anna] Independent Publ Hlth Consultant, Bangalore 560025, Karnataka, India.
[Basu, Partha] Chittaranjan Natl Canc Inst, Kolkata 700026, India.
[Bhatla, Neerja] All India Inst Med Sci, Dept Obstet & Gynaecol, New Delhi 110029, India.
[Birur, Praveen] Biocon Fdn, Bangalore 560100, Karnataka, India.
[Colaco, Rajeev; Nyblade, Laura; Reithinger, Richard; Squiers, Linda] RTI Int, Washington, DC 20005 USA.
[Dey, Subhojit] Indian Inst Publ Hlth Delhi, Publ Hlth Fdn India, Gurgaon 122002, India.
[Grover, Surbhi] Univ Penn, Philadelphia, PA 19104 USA.
[Gupta, Harmala] KanakDurgaBastiVikasKendra, CanSupport, New Delhi 110022, India.
[Gupta, Rakesh] Rajasthan Canc Fdn, Jaipur 302018, Rajasthan, India.
[Gupta, Vandana] Near Tata Mem Hosp, V Care Fdn, Bombay 400012, Maharashtra, India.
[Lewis, Megan A.] RTI Int, Res Triangle Pk, NC 27709 USA.
[Mehrotra, Ravi] Inst Cytol & Prevent Oncol ICMR, Noida 201301, India.
[McMikel, Ann; Naik, Navami] Amer Canc Soc Inc, Atlanta, GA 30303 USA.
[Mukherji, Arnab] IIM Bangalore, Ctr Publ Policy, Bangalore 560076, Karnataka, India.
[Pati, Sanghamitra] Indian Inst Publ Hlth Bhubaneswar, Publ Hlth Fdn India, Bhubaneswar 751024, Orissa, India.
[Pillai, M. Radhakrishna] Govt India Minist Sci & Technol, Rajiv Gandhi Ctr Biotechnol, Thiruvananthapuram 695014, Kerala, India.
[Rajaraman, Preetha] NCI, Ctr Global Hlth, Rockville, MD 20892 USA.
[Ramesh, Chalurvarayaswamy; Vijayakumar, M.] Kidwai Mem Inst Oncol, Bangalore 560029, Karnataka, India.
[Rath, G. K.] All India Inst Med Sci, New Delhi 110029, India.
[Sankaranarayanan, Rengaswamy] WHO IARC, F-69372 Lyon 08, France.
[Selvam, Jerard; Shanmugam, M. S.] Tamil Nadu Hlth Syst Project, Madras 600006, Tamil Nadu, India.
[Siddiqi, Maqsood] Canc Fdn India, Kolkata 700031, India.
[Subramanian, Sujha] RTI Int, Waltham, MA 02451 USA.
[Travasso, Sandra M.] St Johns Res Inst, Bangalore 560034, Karnataka, India.
[Verma, Yogesh] STNM Hosp, Gangtok 737101, Sikkim, Sikkim.
[Weiner, Bryan J.] Univ N Carolina, Gillings Sch Global Publ Hlth, Chapel Hill, NC 27599 USA.
[Reddy, K. Srinath] Publ Hlth Fdn India, Gurgaon 122003, Haryana, India.
RP Krishnan, S (reprint author), Res Triangle Inst Global India Pvt Ltd, Paharpur Business Ctr, Suite 405,21 Nehru Pl, New Delhi 110019, India.
EM skrishnan@rti.org; preet.dhillon@phfi.org
FU RTI International; American Cancer Society
FX This symposium was funded by RTI International and the American Cancer
Society. Travel support was also provided by the Centre for Global
Health, United States National Cancer Institute.
NR 67
TC 1
Z9 1
U1 2
U2 5
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0957-5243
EI 1573-7225
J9 CANCER CAUSE CONTROL
JI Cancer Causes Control
PD NOV
PY 2015
VL 26
IS 11
BP 1671
EP 1684
DI 10.1007/s10552-015-0637-x
PG 14
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA CT3CV
UT WOS:000362685200013
PM 26335262
ER
PT J
AU Yang, YM
Jacoby, E
Fry, TJ
AF Yang, Yinmeng
Jacoby, Elad
Fry, Terry J.
TI Challenges and opportunities of allogeneic donor-derived CAR T cells
SO CURRENT OPINION IN HEMATOLOGY
LA English
DT Review
DE adoptive immunotherapy; allogeneic hematopoietic stem cell
transplantation; chimeric antigen receptors; donor derived;
graft-versus-host disease
ID CHIMERIC-ANTIGEN-RECEPTOR; ACUTE LYMPHOBLASTIC-LEUKEMIA;
VERSUS-HOST-DISEASE; BONE-MARROW-TRANSPLANTATION; ACUTE
MYELOID-LEUKEMIA; NATURAL-KILLER-CELLS; EPSTEIN-BARR-VIRUS;
HEMATOPOIETIC STEM; CANCER-IMMUNOTHERAPY; ADOPTIVE IMMUNOTHERAPY
AB Purpose of reviewAs T cells engineered with chimeric antigen receptors (CARs) are entering advanced phases of clinical trial testing with promising results, the potential implications of use in an allogeneic environment are emerging as an important consideration. This review discusses the use of allogeneic CAR therapy, the potential effects of T-cell receptor (TCR) signaling on CAR T-cell efficacy, and the potential for TCR elimination to generate an off-the-shelf product.Recent findingsThe majority of preclinical and clinical data regarding allogeneic T cells are focused on safety of their use given the potential for graft-versus-host disease (GVHD) mediated by the T-cell receptor expressed with the introduced CAR. Recent clinical trials using donor-derived CAR T cells are using either rigorous patient selection or T-cell selection (such as enrichment for virus-specific T cells). Although no GVHD has been reported, the efficacy of the allogeneic CAR treatment needs to be optimized. Several preclinical models limit allogeneic CAR-driven GVHD by utilizing memory T-cell selection, virus-specific T cells, gene-editing techniques, or suicide gene engineering.SummaryIn the allogeneic environment, the potential effects of TCR signaling on the efficacy of CAR could affect the clinical responses with the use of donor-derived CAR T cells. Better understanding of the functionality of donor-derived T cells for therapy is essential for the development of universal effector cells for CAR therapy.
C1 [Yang, Yinmeng; Jacoby, Elad; Fry, Terry J.] NCI, Pediat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Yang, Yinmeng] Georgetown Univ, Washington, DC 20057 USA.
RP Fry, TJ (reprint author), BG 10-CRC RM 1-3952,10 Ctr Dr, Bethesda, MD 20814 USA.
EM fryt@mail.nih.gov
FU NIH
FX This work was supported by the intramural research program at NIH. 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 U.S. Government.
NR 76
TC 4
Z9 4
U1 1
U2 39
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1065-6251
EI 1531-7048
J9 CURR OPIN HEMATOL
JI Curr. Opin. Hematol.
PD NOV
PY 2015
VL 22
IS 6
BP 509
EP 515
DI 10.1097/MOH.0000000000000181
PG 7
WC Hematology
SC Hematology
GA CT2OI
UT WOS:000362641700008
PM 26390167
ER
PT J
AU Nellan, A
Lee, DW
AF Nellan, Anandani
Lee, Daniel W.
TI Paving the road ahead for CD19 CAR T-cell therapy
SO CURRENT OPINION IN HEMATOLOGY
LA English
DT Review
DE acute lymphoblastic leukemia; CD19; central nervous system leukemia;
chimeric antigen receptor; cytokine release syndrome
ID ACUTE LYMPHOBLASTIC-LEUKEMIA; CHIMERIC ANTIGEN RECEPTORS; ADVERSE EVENT;
TRANSPLANTATION
AB Purpose of reviewModern immunotherapies, most notably in the form of anti-CD19 chimeric antigen receptor (CAR) T cells, have produced significant clinical responses in otherwise refractory pre-B-cell acute lymphoblastic leukemia patients. Several groups have simultaneously reported robust response rates in children and adults alike. These early studies indicate an impending shift in paradigm for the treatment of acute lymphoblastic leukemia. Incorporating CD19 CAR T-cell therapy into upfront or salvage regimens has its challenges and opportunities.Recent findingsMost CD19 CAR T-cell products in trial today are excellent at inducing minimal residual disease negative remissions, and most responding patients experience cytokine release syndrome and/or neurotoxicity. The challenges facing the CAR community involve how best to minimize the severity of cytokine release syndrome and neurotoxicity while maximizing antitumor efficacy, determining what role this therapy will play for the prophylaxis and treatment of central nervous system leukemia, and its implications on subsequent hematopoietic stem cell transplant given the emergence of CD19-negative relapses.SummaryCD19 CAR T-cell therapy is a powerful new tool in the oncologist's arsenal. How it is incorporated into standard practice and how it will shift survival curves are the exciting questions that are waiting to be answered.
C1 [Nellan, Anandani; Lee, Daniel W.] NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA.
RP Lee, DW (reprint author), NCI, Pediat Oncol Branch, 10 Ctr Dr Bldg 10,Room 1-3750,MSC 1104, Bethesda, MD 20892 USA.
EM leed3@mail.nih.gov
FU National Institutes of Health; St. Baldrick's Foundation; Hope From
Harper Fund
FX The authors receive funding from the National Institutes of Health.
D.W.L.'s work was supported in part by a St. Baldrick's Foundation
Scholar Award and with generous support from the Hope From Harper Fund.
NR 16
TC 2
Z9 2
U1 1
U2 31
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1065-6251
EI 1531-7048
J9 CURR OPIN HEMATOL
JI Curr. Opin. Hematol.
PD NOV
PY 2015
VL 22
IS 6
BP 516
EP 520
DI 10.1097/MOH.0000000000000182
PG 5
WC Hematology
SC Hematology
GA CT2OI
UT WOS:000362641700009
PM 26335422
ER
PT J
AU Luis, AD
O'Shea, TJ
Hayman, DTS
Wood, JLN
Cunningham, AA
Gilbert, AT
Mills, JN
Webb, CT
AF Luis, Angela D.
O'Shea, Thomas J.
Hayman, David T. S.
Wood, James L. N.
Cunningham, Andrew A.
Gilbert, Amy T.
Mills, James N.
Webb, Colleen T.
TI Network analysis of host-virus communities in bats and rodents reveals
determinants of cross-species transmission
SO ECOLOGY LETTERS
LA English
DT Article
DE Chiroptera; ecological networks; emerging infectious disease; Rodentia;
zoonoses
ID EMERGING INFECTIOUS-DISEASES; EVOLUTION; PARASITES; PHYLOGENY;
RESERVOIR; PATTERNS; MATRICES; ECOLOGY; PACKAGE
AB Bats are natural reservoirs of several important emerging viruses. Cross-species transmission appears to be quite common among bats, which may contribute to their unique reservoir potential. Therefore, understanding the importance of bats as reservoirs requires examining them in a community context rather than concentrating on individual species. Here, we use a network approach to identify ecological and biological correlates of cross-species virus transmission in bats and rodents, another important host group. We show that given our current knowledge the bat viral sharing network is more connected than the rodent network, suggesting viruses may pass more easily between bat species. We identify host traits associated with important reservoir species: gregarious bats are more likely to share more viruses and bats which migrate regionally are important for spreading viruses through the network. We identify multiple communities of viral sharing within bats and rodents and highlight potential species traits that can help guide studies of novel pathogen emergence.
C1 [Luis, Angela D.; Hayman, David T. S.; Webb, Colleen T.] Colorado State Univ, Dept Biol, Ft Collins, CO 80523 USA.
[Luis, Angela D.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Luis, Angela D.] Univ Montana, Dept Ecosyst & Conservat Sci, Wildlife Biol Program, Missoula, MT 59812 USA.
[O'Shea, Thomas J.] US Geol Survey, Ft Collins Sci Ctr, Ft Collins, CO 80526 USA.
[Hayman, David T. S.] Univ Florida, Dept Biol, Gainesville, FL 32611 USA.
[Hayman, David T. S.] Massey Univ, mEpiLab, Infect Dis Res Ctr IDReC, Hopkirk Res Inst,Inst Vet Anim & Biomed Sci, Palmerston North 4442, Manawatu, New Zealand.
[Wood, James L. N.] Univ Cambridge, Dis Dynam Unit, Dept Vet Med, Cambridge CB3 0ES, England.
[Cunningham, Andrew A.] Zool Soc London, Inst Zool, London NW1 4RY, England.
[Gilbert, Amy T.] USDA, Natl Wildlife Res Ctr, Ft Collins, CO 80521 USA.
[Mills, James N.] Emory Univ, Populat Biol Ecol & Evolut Program, Atlanta, GA 30322 USA.
RP Luis, AD (reprint author), Colorado State Univ, Dept Biol, Ft Collins, CO 80523 USA.
EM angela.luis@umontana.edu
RI Cunningham, Andrew/E-7536-2010; Wood, James/A-1626-2008
OI Wood, James/0000-0002-0258-3188
FU Research and Policy for Infectious Disease Dynamics (RAPIDD) program of
the Science and Technology Directorate (US Department of Homeland
Security); Fogarty International Center (National Institutes of Health);
David H. Smith post-doctoral fellowship; Royal Society Wolfson Research
Merit award; Alborada Trust
FX This work was supported by the Research and Policy for Infectious
Disease Dynamics (RAPIDD) program of the Science and Technology
Directorate (US Department of Homeland Security) and the Fogarty
International Center (National Institutes of Health). D.T.S.H.
acknowledges funding from a David H. Smith post-doctoral fellowship.
A.A.C. is partially funded by a Royal Society Wolfson Research Merit
award, and J.L.N.W. is supported by the Alborada Trust. Thanks to Paul
Cryan and Michael O'Donnell of the USGS Fort Collins Science Center for
help with species distribution analyses.
NR 47
TC 8
Z9 8
U1 14
U2 66
PU WILEY
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1461-023X
EI 1461-0248
J9 ECOL LETT
JI Ecol. Lett.
PD NOV
PY 2015
VL 18
IS 11
BP 1153
EP 1162
DI 10.1111/ele.12491
PG 10
WC Ecology
SC Environmental Sciences & Ecology
GA CT6IB
UT WOS:000362915600002
ER
PT J
AU Freedman, LS
Midthune, D
Carroll, RJ
Commins, JM
Arab, L
Baer, DJ
Moler, JE
Moshfegh, AJ
Neuhouser, ML
Prentice, RL
Rhodes, D
Spiegelman, D
Subar, AF
Tinker, LF
Willett, W
Kipnis, V
AF Freedman, Laurence S.
Midthune, Douglas
Carroll, Raymond J.
Commins, John M.
Arab, Lenore
Baer, David J.
Moler, James E.
Moshfegh, Alanna J.
Neuhouser, Marian L.
Prentice, Ross L.
Rhodes, Donna
Spiegelman, Donna
Subar, Amy F.
Tinker, Lesley F.
Willett, Walter
Kipnis, Victor
TI Application of a New Statistical Model for Measurement Error to the
Evaluation of Dietary Self-report Instruments
SO EPIDEMIOLOGY
LA English
DT Article
ID FOOD FREQUENCY QUESTIONNAIRE; WITHIN-PERSON VARIATION; RECOVERY
BIOMARKERS; NUTRITIONAL EPIDEMIOLOGY; ENERGY-EXPENDITURE; SODIUM-INTAKE;
POTASSIUM INTAKE; 2 VALIDATION; PROTEIN; RECALLS
AB Most statistical methods that adjust analyses for dietary measurement error treat an individual's usual intake as a fixed quantity. However, usual intake, if defined as average intake over a few months, varies over time. We describe a model that accounts for such variation and for the proximity of biomarker measurements to self-reports within the framework of a meta-analysis, and apply it to the analysis of data on energy, protein, potassium, and sodium from a set of five large validation studies of dietary self-report instruments using recovery biomarkers as reference instruments. We show that this time-varying usual intake model fits the data better than the fixed usual intake assumption. Using this model, we estimated attenuation factors and correlations with true longer-term usual intake for single and multiple 24-hour dietary recalls (24HRs) and food frequency questionnaires (FFQs) and compared them with those obtained under the fixed method. Compared with the fixed method, the estimates using the time-varying model showed slightly larger values of the attenuation factor and correlation coefficient for FFQs and smaller values for 24HRs. In some cases, the difference between the fixed method estimate and the new estimate for multiple 24HRs was substantial. With the new method, while four 24HRs had higher estimated correlations with truth than a single FFQ for absolute intakes of protein, potassium, and sodium, for densities the correlations were approximately equal. Accounting for the time element in dietary validation is potentially important, and points toward the need for longer-term validation studies.
C1 [Freedman, Laurence S.; Commins, John M.; Moler, James E.] Informat Management Serv Inc, Rockville, MD USA.
[Midthune, Douglas; Subar, Amy F.; Kipnis, Victor] NCI, Bethesda, MD 20892 USA.
[Carroll, Raymond J.] Texas A&M Univ, College Stn, TX USA.
[Arab, Lenore] Univ Calif Los Angeles, Los Angeles, CA USA.
[Baer, David J.; Moshfegh, Alanna J.; Rhodes, Donna] USDA, Beltsville, MD 20705 USA.
[Neuhouser, Marian L.; Prentice, Ross L.; Tinker, Lesley F.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Spiegelman, Donna; Willett, Walter] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
RP Freedman, LS (reprint author), Sheba Med Ctr, Gertner Inst Epidemiol, IL-52621 Tel Hashomer, Israel.
EM lsf@actcom.co.il
OI Moler, James/0000-0001-8738-6898
FU National Heart, Lung, and Blood Institute, National Institutes of
Health, US Department of Health and Human Services [HHSN268201100046C,
HHSN268201100001C, HHSN268201100002C, HHSN268201100003C,
HHSN268201100004C, HHSN271201100004C]
FX The Women's Health Initiative program is funded by the National Heart,
Lung, and Blood Institute, National Institutes of Health, US Department
of Health and Human Services through contracts HHSN268201100046C,
HHSN268201100001C, HHSN268201100002C, HHSN268201100003C,
HHSN268201100004C, and HHSN271201100004C.
NR 39
TC 3
Z9 3
U1 0
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1044-3983
EI 1531-5487
J9 EPIDEMIOLOGY
JI Epidemiology
PD NOV
PY 2015
VL 26
IS 6
BP 925
EP 933
DI 10.1097/EDE.0000000000000377
PG 9
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA CT1JF
UT WOS:000362553900020
PM 26360372
ER
PT J
AU Mariosa, D
Kamel, F
Bellocco, R
Ye, W
Fang, F
AF Mariosa, D.
Kamel, F.
Bellocco, R.
Ye, W.
Fang, F.
TI Association between diabetes and amyotrophic lateral sclerosis in Sweden
SO EUROPEAN JOURNAL OF NEUROLOGY
LA English
DT Article
DE amyotrophic lateral sclerosis; diabetes; epidemiology; insulin
dependence; metabolic and endocrine disorders; motor neuron disease;
neurological disorders; neuromuscular diseases; research methods
ID RISK; MELLITUS
AB Background and purposeEnergy metabolism is altered in patients with amyotrophic lateral sclerosis (ALS) but the role of diabetes is largely unknown.
MethodsA population-based case-control study was conducted of 5108 ALS cases and 25540 individually matched population controls during 1991-2010. Information on ALS and pre-existing diabetes was retrieved from the Swedish Patient Register to explore the association of ALS with diabetes overall and with insulin-dependent or non-insulin-dependent diabetes specifically. Variation of the association by diabetes duration and age was also studied.
ResultsIn total, 224 ALS cases (4.39%) and 1437 controls (5.63%) had diabetes before the index date, leading to an overall inverse association between diabetes and ALS risk [odds ratio (OR)0.79, 95% confidence interval (CI)0.68-0.91]. The association was strong for non-insulin-dependent diabetes (OR0.66, 95% CI0.53-0.81) but not for insulin-dependent diabetes (OR0.83, 95% CI0.60-1.15) and varied as a function of diabetes duration, with the strongest association observed around 6years after first ascertainment of diabetes. The association was age-specific; the inverse association was noted only amongst individuals aged 70 or older. In contrast, for younger individuals (<50years), pre-existing insulin-dependent diabetes was associated with a higher ALS risk (OR5.38, 95% CI1.87-15.51).
ConclusionsOur study suggests that there is an association between diabetes and ALS, and highlights the importance of taking into account age, insulin dependence and diabetes duration. Future studies should explore whether the association is independent of body mass index.
Click to view the accompanying paper in this issue.
C1 [Mariosa, D.; Bellocco, R.; Ye, W.; Fang, F.] Karolinska Inst, Dept Med Epidemiol & Biostat, S-17177 Stockholm, Sweden.
[Kamel, F.] Natl Inst Environm Hlth Sci, Epidemiol Branch, Res Triangle Pk, NC USA.
[Bellocco, R.] Univ Milano Bicocca, Dept Stat & Quantitat Methods, Milan, Italy.
RP Mariosa, D (reprint author), Karolinska Inst, Dept Med Epidemiol & Biostat, Box 281, S-17177 Stockholm, Sweden.
EM Daniela.mariosa@ki.se
OI Fang, Fang/0000-0002-3310-6456; Kamel, Freya/0000-0001-5052-6615
FU Swedish Research Council; Swedish Society for Medical Research; Swedish
Research Council for Health, Working Life and Welfare; Karolinska
Institutet Partial Finance for PhD Students; NIH [Z01 ES 049005]
FX This study was funded by the Swedish Research Council, the Swedish
Society for Medical Research, the Swedish Research Council for Health,
Working Life and Welfare, the Karolinska Institutet Partial Finance for
PhD Students, and the Intramural Research Program of the NIH (Z01 ES
049005).
NR 25
TC 10
Z9 11
U1 0
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1351-5101
EI 1468-1331
J9 EUR J NEUROL
JI Eur. J. Neurol.
PD NOV
PY 2015
VL 22
IS 11
BP 1436
EP 1442
DI 10.1111/ene.12632
PG 7
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA CT2YR
UT WOS:000362673300004
PM 25600257
ER
PT J
AU Bluher, A
Devan, WJ
Holliday, EG
Nalls, M
Parolo, S
Bione, S
Giese, AK
Boncoraglio, GB
Maguire, JM
Muller-Nurasyid, M
Gieger, C
Meschia, JF
Rosand, J
Rolfs, A
Kittner, SJ
Mitchell, BD
O'Connell, JR
Cheng, YC
AF Bluher, A.
Devan, W. J.
Holliday, E. G.
Nalls, M.
Parolo, S.
Bione, S.
Giese, A. -K.
Boncoraglio, G. B.
Maguire, J. M.
Mueller-Nurasyid, M.
Gieger, C.
Meschia, J. F.
Rosand, J.
Rolfs, A.
Kittner, S. J.
Mitchell, B. D.
O'Connell, J. R.
Cheng, Y. -C.
TI Heritability of young- and old-onset ischaemic stroke
SO EUROPEAN JOURNAL OF NEUROLOGY
LA English
DT Article
DE heritability; ischemic stroke; stroke
ID HISTORY; WOMEN; RISK
AB Background and purposeAlthough the genetic contribution to stroke risk is well known, it remains unclear if young-onset stroke has a stronger genetic contribution than old-onset stroke. This study aims to compare the heritability of ischaemic stroke risk between young and old, using common genetic variants from whole-genome array data in population-based samples.
MethodsThis analysis included 4050 ischaemic stroke cases and 5765 controls from six study populations of European ancestry; 47% of cases were young-onset stroke (age<55years). To quantify the heritability for stroke risk in these unrelated individuals, the pairwise genetic relatedness was estimated between individuals based on their whole-genome array data using a mixed linear model. Heritability was estimated separately for young-onset stroke and old-onset stroke (age55years).
ResultsHeritabilities for young-onset stroke and old-onset stroke were estimated at 42% (8%, P<0.001) and 34% (+/- 10%, P<0.001), respectively.
ConclusionsOur data suggest that the genetic contribution to the risk of stroke may be higher in young-onset ischaemic stroke, although the difference was not statistically significant.
C1 [Bluher, A.; Kittner, S. J.] Univ Maryland, Sch Med, Dept Neurol, Baltimore, MD 21201 USA.
[Devan, W. J.; Rosand, J.] Univ Maryland, Sch Med, Massachusetts Gen Hosp, Dept Neurol,Stroke Serv, Baltimore, MD 21201 USA.
[Devan, W. J.; Rosand, J.] Univ Maryland, Sch Med, Massachusetts Gen Hosp, Ctr Human Genet Res, Baltimore, MD 21201 USA.
[Holliday, E. G.] Hunter Med Res Inst, Publ Hlth Program, Newcastle, NSW, Australia.
[Holliday, E. G.] Univ Newcastle, Sch Med & Publ Hlth, Newcastle, NSW, Australia.
[Nalls, M.] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
[Parolo, S.; Bione, S.] CNR, Inst Mol Genet, Pavia, Italy.
[Giese, A. -K.; Rolfs, A.] Univ Rostock, Albrecht Kossel Inst Neuroregenerat, Rostock, Germany.
[Boncoraglio, G. B.] Ist Neurol Carlo Besta, Fdn IRCCS, Dept Cerebrovasc Dis, Milan, Italy.
[Maguire, J. M.] Univ Newcastle, Sch Nursing & Midwifery, Newcastle, NSW 2300, Australia.
[Mueller-Nurasyid, M.] Helmholtz Zentrum Munchen German Res Ctr Environm, Neuherberg, Germany.
[Mueller-Nurasyid, M.] Univ Munich, Dept Med 1, Munich, Germany.
[Mueller-Nurasyid, M.] Partner Site Munich Heart Alliance, DZHK German Ctr Cardiovas Res, Munich, Germany.
[Gieger, C.] Helmholtz Zentrum Munchen German Res Ctr Environm, Res Unit Mol Epidemiol, Neuherberg, Germany.
[Gieger, C.] Helmholtz Zentrum Munchen German Res Ctr Environm, Inst Epidemiol 2, Neuherberg, Germany.
[Meschia, J. F.] Mayo Clin, Dept Neurol, Jacksonville, FL USA.
[Kittner, S. J.] Vet Affairs Maryland Hlth Care Syst, Dept Neurol, Baltimore, MD USA.
[Mitchell, B. D.; O'Connell, J. R.; Cheng, Y. -C.] Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA.
[Mitchell, B. D.] Vet Affairs Maryland Hlth Care Syst, Geriatr Res & Educ Clin Ctr, Baltimore, MD USA.
[Cheng, Y. -C.] Vet Affairs Maryland Hlth Care Syst, Res & Dev Program, Baltimore, MD USA.
RP Mitchell, BD (reprint author), 685 W Baltimore St,MSTF 302, Baltimore, MD 21201 USA.
EM bmitchel@medicine.umaryland.edu
RI Boncoraglio, Giorgio/B-8647-2011;
OI Bione, Silvia/0000-0002-3924-4606; Parolo, Silvia/0000-0002-3671-5353;
Gieger, Christian/0000-0001-6986-9554; Mitchell,
Braxton/0000-0003-4920-4744
FU US Department of Veterans Affairs [1IK2BX001823]; US National Institute
of Health [U01 HG004436, U01 NS069208, P30 DK072488, 5U01NS069208]; US
National Institute of Health (NIA) [Z01 AG-000954-06]; Australian
National Health and Medical Research Council (NHMRC) [569257];
Australian National Heart Foundation (NHF) [G 04S 1623]; Cariplo
Foundation [2010/0253]; Italian Ministry of Health [RC 2007/LR6, RC
2008/LR6, RC 2009/LR8, RC 2010/LR8]; Australian Heart Foundation
[100071]; National Stroke Foundation; [FP6 LSHM-CT-2007-037273]
FX This work was supported in part by funding from the US Department of
Veterans Affairs (1IK2BX001823 to Y.C. and a Merit Review Award to
S.J.K), US National Institute of Health (grants U01 HG004436, U01
NS069208 and P30 DK072488, 5U01NS069208, NIA intramural project Z01
AG-000954-06), the Australian National Health and Medical Research
Council (NHMRC; project grant 569257), the Australian National Heart
Foundation (NHF; project grant G 04S 1623), the Cariplo Foundation
(grant no. 2010/0253) and the Italian Ministry of Health (grant no. RC
2007/LR6, RC 2008/LR6; RC 2009/LR8; RC 2010/LR8). The PROCARDIS control
samples were funded by FP6 LSHM-CT-2007-037273. E.G.H. is supported by a
fellowship (100071) from the Australian Heart Foundation and National
Stroke Foundation.
NR 10
TC 2
Z9 2
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1351-5101
EI 1468-1331
J9 EUR J NEUROL
JI Eur. J. Neurol.
PD NOV
PY 2015
VL 22
IS 11
BP 1488
EP 1491
DI 10.1111/ene.12827
PG 4
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA CT2YR
UT WOS:000362673300011
PM 26333310
ER
PT J
AU Nita-Lazar, A
Mann, JM
Laky, K
Fraser, IDC
Li, N
AF Nita-Lazar, Aleksandra
Mann, Jessica M.
Laky, Karen
Fraser, Iain D. C.
Li, Ning
TI Analysis of protein O-fucosyltransferase 1 regulation of Toll-like
receptor signaling in macrophages
SO GLYCOBIOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the Society-for-Glycobiology on Glycobiology -
Accelerating Impact across the Biomedical Sciences
CY DEC 01-04, 2015
CL San Francisco, CA
SP Soc Glycobiol
C1 [Nita-Lazar, Aleksandra; Mann, Jessica M.] NIAID, Cellular Networks Prote Unit, Lab Syst Biol, NIH, Bethesda, MD USA.
[Fraser, Iain D. C.; Li, Ning] NIAID, Signaling Syst Unit, Lab Syst Biol, NIH, Bethesda, MD USA.
[Laky, Karen] NIAID, Signaling Syst Unit, Lab Syst Biol, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0959-6658
EI 1460-2423
J9 GLYCOBIOLOGY
JI Glycobiology
PD NOV
PY 2015
VL 25
IS 11
MA 4
BP 1230
EP 1230
PG 1
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA CT7JR
UT WOS:000362991500011
ER
PT J
AU Lingwood, D
Villar, RF
Patel, J
Kanekiyo, M
Wheatley, AK
Nabel, GJ
Mascola, JR
Carr, SA
AF Lingwood, Daniel
Villar, Rina F.
Patel, Jinal
Kanekiyo, Masaru
Wheatley, Adam K.
Nabel, Gary J.
Mascola, John R.
Carr, Steven A.
TI Viral lectin initiates B cell Activation and Signaling
SO GLYCOBIOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the Society-for-Glycobiology on Glycobiology -
Accelerating Impact across the Biomedical Sciences
CY DEC 01-04, 2015
CL San Francisco, CA
SP Soc Glycobiol
C1 [Lingwood, Daniel; Villar, Rina F.] Ragon Inst MGH MIT & Harvard, Cambridge, MA USA.
[Kanekiyo, Masaru; Wheatley, Adam K.; Nabel, Gary J.; Mascola, John R.] NIH, Vaccine Res Ctr, Stapleton, NY USA.
[Patel, Jinal; Carr, Steven A.] Broad Inst MIT & Harvard, Cambridge, MA USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
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 NOV
PY 2015
VL 25
IS 11
MA 23
BP 1235
EP 1236
PG 2
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA CT7JR
UT WOS:000362991500026
ER
PT J
AU Gildersleeve, J
AF Gildersleeve, Jeffrey
TI Serum Anti-Glycan Antibodies as Immunotherapy Biomarkers
SO GLYCOBIOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the Society-for-Glycobiology on Glycobiology -
Accelerating Impact across the Biomedical Sciences
CY DEC 01-04, 2015
CL San Francisco, CA
SP Soc Glycobiol
C1 [Gildersleeve, Jeffrey] NCI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
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 NOV
PY 2015
VL 25
IS 11
MA 35
BP 1238
EP 1239
PG 2
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA CT7JR
UT WOS:000362991500034
ER
PT J
AU Tabak, LA
Beck, L
Patel, K
Ajinkya, M
Rojas, R
AF Tabak, Lawrence A.
Beck, Lauren
Patel, Kanishka
Ajinkya, Monica
Rojas, Raul
TI Growth factors do not mediate Golgi-to-ER relocation of GalNAc-Ts
SO GLYCOBIOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the Society-for-Glycobiology on Glycobiology -
Accelerating Impact across the Biomedical Sciences
CY DEC 01-04, 2015
CL San Francisco, CA
SP Soc Glycobiol
C1 [Tabak, Lawrence A.; Beck, Lauren; Patel, Kanishka; Ajinkya, Monica; Rojas, Raul] Natl Inst Dent & Craniofacial Res, Sect Biol Chem, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0959-6658
EI 1460-2423
J9 GLYCOBIOLOGY
JI Glycobiology
PD NOV
PY 2015
VL 25
IS 11
MA 120
BP 1269
EP 1269
PG 1
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA CT7JR
UT WOS:000362991500114
ER
PT J
AU Akan, I
Hanover, JA
AF Akan, Ilhan
Hanover, John A.
TI O-GlcNAcase is an epigenetic regulator of Drosophila development
SO GLYCOBIOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the Society-for-Glycobiology on Glycobiology -
Accelerating Impact across the Biomedical Sciences
CY DEC 01-04, 2015
CL San Francisco, CA
SP Soc Glycobiol
C1 [Akan, Ilhan; Hanover, John A.] NIDDK, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
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 NOV
PY 2015
VL 25
IS 11
MA 164
BP 1286
EP 1286
PG 1
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA CT7JR
UT WOS:000362991500158
ER
PT J
AU Hanover, JA
Cheng, CM
Love, DC
Bondy, C
Gharib, AM
AF Hanover, John A.
Cheng, Clara M.
Love, Dona C.
Bondy, Carolyn
Gharib, Ahmed M.
TI Deregulated O-GlcNAc Cycling in Turner Syndrome
SO GLYCOBIOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the Society-for-Glycobiology on Glycobiology -
Accelerating Impact across the Biomedical Sciences
CY DEC 01-04, 2015
CL San Francisco, CA
SP Soc Glycobiol
C1 [Hanover, John A.; Love, Dona C.; Gharib, Ahmed M.] NIDDK, NIH, Bethesda, MD 20892 USA.
[Cheng, Clara M.; Bondy, Carolyn] NICHD, NIH, Bethesda, MD USA.
RI Gharib, Ahmed/O-2629-2016
OI Gharib, Ahmed/0000-0002-2476-481X
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0959-6658
EI 1460-2423
J9 GLYCOBIOLOGY
JI Glycobiology
PD NOV
PY 2015
VL 25
IS 11
MA 166
BP 1286
EP 1287
PG 2
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA CT7JR
UT WOS:000362991500160
ER
PT J
AU Bond, MR
Hanover, JA
AF Bond, Michelle R.
Hanover, John A.
TI O-GlcNAc transferase is required for fidelity in C. elegans development
SO GLYCOBIOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the Society-for-Glycobiology on Glycobiology -
Accelerating Impact across the Biomedical Sciences
CY DEC 01-04, 2015
CL San Francisco, CA
SP Soc Glycobiol
C1 [Bond, Michelle R.; Hanover, John A.] Natl Inst Hlth, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
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 NOV
PY 2015
VL 25
IS 11
MA 167
BP 1287
EP 1287
PG 1
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA CT7JR
UT WOS:000362991500161
ER
PT J
AU Huizing, M
Okafor, O
Zerfas, PM
Bodine, S
Starost, MF
Gahl, WA
Kopp, JB
Malicdan, MCV
AF Huizing, Marjan
Okafor, Obiageri
Zerfas, Patricia M.
Bodine, Steven
Starost, Matthew F.
Gahl, William A.
Kopp, Jeffrey B.
Malicdan, May Christine V.
TI N-Acetylmannosamine Mitigates Neuraminidase-induced Podocyte Injury in
Mice
SO GLYCOBIOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the Society-for-Glycobiology on Glycobiology -
Accelerating Impact across the Biomedical Sciences
CY DEC 01-04, 2015
CL San Francisco, CA
SP Soc Glycobiol
C1 [Huizing, Marjan; Okafor, Obiageri; Bodine, Steven; Gahl, William A.; Malicdan, May Christine V.] NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA.
[Zerfas, Patricia M.; Starost, Matthew F.] NIH, Off Res Serv, OD, Bethesda, MD 20892 USA.
[Kopp, Jeffrey B.] NIDDK, Kidney Dis Sect, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
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 NOV
PY 2015
VL 25
IS 11
MA 212
BP 1303
EP 1304
PG 2
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA CT7JR
UT WOS:000362991500206
ER
PT J
AU Zhang, LP
ten Hagen, KG
AF Zhang, Liping
ten Hagen, Kelly G.
TI O-glycosylation is required for peritrophic membrane formation to
maintain gut homeostasis in Drosophila
SO GLYCOBIOLOGY
LA English
DT Meeting Abstract
CT Annual Meeting of the Society-for-Glycobiology on Glycobiology -
Accelerating Impact across the Biomedical Sciences
CY DEC 01-04, 2015
CL San Francisco, CA
SP Soc Glycobiol
C1 [Zhang, Liping; ten Hagen, Kelly G.] Natl Inst Dent & Craniofacial Res, Dev Glycobiol Sect, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0959-6658
EI 1460-2423
J9 GLYCOBIOLOGY
JI Glycobiology
PD NOV
PY 2015
VL 25
IS 11
MA 214
BP 1304
EP 1304
PG 1
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA CT7JR
UT WOS:000362991500208
ER
PT J
AU Liu, S
Saloustros, E
Mertz, EL
Tsang, K
Starost, MF
Salpea, P
Faucz, FR
Szarek, E
Nesterova, M
Leikin, S
Stratakis, CA
AF Liu, Sisi
Saloustros, Emmanouil
Mertz, Edward L.
Tsang, Kitman
Starost, Matthew F.
Salpea, Paraskevi
Faucz, Fabio R.
Szarek, Eva
Nesterova, Maria
Leikin, Sergey
Stratakis, Constantine A.
TI Haploinsufficiency for either one of the type-II regulatory subunits of
protein kinase A improves the bone phenotype of Prkar1a(+/-) mice
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID DENTIN MATRIX PROTEIN-1; DIFFERENTIATION IN-VITRO; MCCUNE-ALBRIGHT
SYNDROME; STIMULATORY G-PROTEIN; OSTEOBLAST DIFFERENTIATION; CARNEY
COMPLEX; GENE-TRANSCRIPTION; SKELETAL DEVELOPMENT; ALPHA-SUBUNIT;
STROMAL CELLS
AB Carney Complex (CNC), a human genetic syndrome predisposing to multiple neoplasias, is associated with bone lesions such as osteochondromyxomas (OMX). The most frequent cause for CNC is PRKAR1A deficiency; PRKAR1A codes for type-I regulatory subunit of protein kinase A (PKA). Prkar1a(+/-) mice developed OMX, fibrous dysplasia-like lesions (FDL) and other tumors. Tumor tissues in these animals had increased PKA activity due to an unregulated PKA catalytic subunit and increased PKA type II (PKAII) activity mediated by the PRKAR2A and PRKAR2B subunits. To better understand the effect of altered PKA activity on bone, we studied Prkar2a and Prkar2b knock out (KO) and heterozygous mice; none of these mice developed bone lesions. When Prkar2a(+/-) and Prkar2b(+/-) mice were used to generate Prkar1a(+/-) Prkar2a(+/-) and Prkar1a(+/-) Prkar2b(+/-) animals, bone lesions formed that looked like those of the Prkar1a(+/-) mice. However, better overall bone organization and mineralization and fewer FDL lesions were found in both double heterozygote groups, indicating a partial restoration of the immature bone structure observed in Prkar1a(+/-) mice. Further investigation indicated increased osteogenesis and higher new bone formation rates in both Prkar1a(+/-) Prkar2a(+/-) and Prkar1a(+/-) Prkar2b(+/-) mice with some minor differences between them. The observations were confirmed with a variety of markers and studies. PKA activity measurements showed the expected PKA-II decrease in both double heterozygote groups. Thus, haploinsufficiency for either of PKA-II regulatory subunits improved bone phenotype of mice haploinsufficient for Prkar1a, in support of the hypothesis that the PRKAR2A and PRKAR2B regulatory subunits were in part responsible for the bone phenotype of Prkar1a(+/-) mice.
C1 [Liu, Sisi; Saloustros, Emmanouil; Tsang, Kitman; Salpea, Paraskevi; Faucz, Fabio R.; Szarek, Eva; Nesterova, Maria; Stratakis, Constantine A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrinol & Genet SEGEN, Program Dev Endocrinol & Genet PDEGEN, Bethesda, MD 20892 USA.
[Mertz, Edward L.; Leikin, Sergey] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Phys Biochem, Off Sci Director, Bethesda, MD 20892 USA.
[Starost, Matthew F.] NIH, ORS, DVR, OD, Bethesda, MD 20892 USA.
RP Stratakis, CA (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrinol & Genet SEGEN, Program Dev Endocrinol & Genet PDEGEN, NIH, Bethesda, MD 20892 USA.
EM stratakc@mail.nih.gov
RI Leikin, Sergey/A-5518-2008
OI Leikin, Sergey/0000-0001-7095-0739
FU Intramural Research Program (IRP) of the Eunice Kennedy Shriver National
Institute of Child Health & Human Development (NICHD), National
Institutes of Health (NIH), Bethesda, MD, USA
FX This work was supported by the Intramural Research Program (IRP) of the
Eunice Kennedy Shriver National Institute of Child Health & Human
Development (NICHD), National Institutes of Health (NIH), Bethesda, MD
20892, USA.
NR 55
TC 2
Z9 2
U1 1
U2 3
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 NOV 1
PY 2015
VL 24
IS 21
BP 6080
EP 6092
DI 10.1093/hmg/ddv320
PG 13
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA CT7WA
UT WOS:000363024000011
PM 26246497
ER
PT J
AU Bianchi, L
Gagliardi, A
Maruelli, S
Besio, R
Landi, C
Gioia, R
Kozloff, KM
Khoury, BM
Coucke, PJ
Symoens, S
Marini, JC
Rossi, A
Bini, L
Forlino, A
AF Bianchi, Laura
Gagliardi, Assunta
Maruelli, Silvia
Besio, Roberta
Landi, Claudia
Gioia, Roberta
Kozloff, Kenneth M.
Khoury, Basma M.
Coucke, Paul J.
Symoens, Sofie
Marini, Joan C.
Rossi, Antonio
Bini, Luca
Forlino, Antonella
TI Altered cytoskeletal organization characterized lethal but not surviving
Brtl(+/-) mice: insight on phenotypic variability in osteogenesis
imperfecta
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID GROWTH-FACTOR-BETA; OSTEOBLAST DIFFERENTIATION; MURINE MODEL; MOUSE
MODEL; I COLLAGEN; INTERMEDIATE-FILAMENTS; INTEGRIN RECEPTORS; ACTIN
DYNAMICS; CELL-SHAPE; PROTEINS
AB Osteogenesis imperfecta (OI) is a heritable bone disease with dominant and recessive transmission. It is characterized by a wide spectrum of clinical outcomes ranging from very mild to lethal in the perinatal period. The intra- and inter-familiar OI phenotypic variability in the presence of an identical molecular defect is still puzzling to the research field. We used the OI murine model Brtl(+/-) to investigate the molecular basis of OI phenotypic variability. Brtl(+/-) resembles classical dominant OI and shows either a moderately severe or a lethal outcome associated with the same Gly349Cys substitution in the alpha 1 chain of type I collagen. A systems biology approach was used. We took advantage of proteomic pathway analysis to functionally link proteins differentially expressed in bone and skin of Brtl(+/-) mice with different outcomes to define possible phenotype modulators. The skin/bone and bone/skin hybrid networks highlighted three focal proteins: vimentin, stathmin and cofilin-1, belonging to or involved in cytoskeletal organization. Abnormal cytoskeleton was indeed demonstrated by immunohistochemistry to occur only in tissues from Brtl(+/-) lethal mice. The aberrant cytoskeleton affected osteoblast proliferation, collagen deposition, integrin and TGF-beta signaling with impairment of bone structural properties. Finally, aberrant cytoskeletal assembly was detected in fibroblasts obtained from lethal, but not from non-lethal, OI patients carrying an identical glycine substitution. Our data demonstrated that compromised cytoskeletal assembly impaired both cell signaling and cellular trafficking in mutant lethal mice, altering bone properties. These results point to the cytoskeleton as a phenotypic modulator and potential novel target for OI treatment.
C1 [Bianchi, Laura; Gagliardi, Assunta; Landi, Claudia; Bini, Luca] Univ Siena, Dept Life Sci, Funct Prote Lab, I-53100 Siena, Italy.
[Maruelli, Silvia; Besio, Roberta; Gioia, Roberta; Rossi, Antonio; Forlino, Antonella] Univ Pavia, Biochem Unit, Dept Mol Med, I-27100 Pavia, Italy.
[Kozloff, Kenneth M.; Khoury, Basma M.] Univ Michigan, Dept Orthopaed Surg, Orthopaed Res Labs, Ann Arbor, MI 48109 USA.
[Coucke, Paul J.; Symoens, Sofie] Univ Ghent, Ctr Med Genet, B-9000 Ghent, Belgium.
[Marini, Joan C.] NICHD, Bone & Extracellular Matrix Branch, NIH, Bethesda, MD USA.
RP Forlino, A (reprint author), Univ Pavia, Biochem Unit, Dept Mol Med, Via Taramelli 3-B, I-27100 Pavia, Italy.
EM aforlino@unipv.it
FU Fondazione Cariplo [2013-0612]; Telethon [GGP13098]; European Community
[602300]
FX The work was supported by Fondazione Cariplo (grant No. 2013-0612),
Telethon (grant No. GGP13098) and the European Community, FP7, 'Sybil'
project (grant No. 602300).
NR 53
TC 1
Z9 1
U1 0
U2 5
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 NOV 1
PY 2015
VL 24
IS 21
BP 6118
EP 6133
DI 10.1093/hmg/ddv328
PG 16
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA CT7WA
UT WOS:000363024000014
PM 26264579
ER
PT J
AU Geiger, SS
Fagundes, CT
Siegel, RM
AF Geiger, Sarah S.
Fagundes, Caio T.
Siegel, Richard M.
TI Chrono-immunology: progress and challenges in understanding links
between the circadian and immune systems
SO IMMUNOLOGY
LA English
DT Review
DE circadian; cytokines; immunity; metabolism; sleep
ID FOOD-ANTICIPATORY ACTIVITY; NECROSIS-FACTOR-ALPHA; HIGH-FAT DIET;
SUPRACHIASMATIC NUCLEUS; INFLAMMATORY CYTOKINES; RHEUMATOID-ARTHRITIS;
DIURNAL-VARIATION; CLOCK PROTEIN; T-CELL; SLEEP
AB Development of inflammatory diseases, such as metabolic syndrome and cancer, is prevalent in individuals that encounter continuous disruption of their internal clock. Further, daily oscillations in susceptibility to infection as well as a multitude of other immunological processes have been described. Much progress has been made and various mechanisms have been proposed to explain circadian variations in immunity; yet much is still unknown. Understanding the crosstalk between the circadian and the immune systems will allow us to manipulate clock outputs to prevent and treat inflammatory diseases in individuals at risk. This review briefly summarizes current knowledge about circadian rhythms and their role in the immune system and highlights progress and challenges in chrono-immunological research.
C1 [Geiger, Sarah S.; Siegel, Richard M.] NIAMS, Immunoregulat Sect, Autoimmun Branch, NIH, Bethesda, MD 20892 USA.
[Fagundes, Caio T.] Univ Fed Minas Gerais, Inst Ciencias Biol, Dept Microbiol, Microorganism Host Interact, Belo Horizonte, MG, Brazil.
RP Geiger, SS (reprint author), NIAMS, NIH, 9000 Rockville Pike,Bldg 10,Room 13C213, Bethesda, MD 20892 USA.
EM sarah.sofia.geiger@gmail.com
FU Wellcome Trust; National Institute of Arthritis and Musculoskeletal and
Skin Diseases of the U.S. National Institutes of Health
FX This work was supported by the Wellcome Trust and the intramural
research funding from the National Institute of Arthritis and
Musculoskeletal and Skin Diseases of the U.S. National Institutes of
Health. The authors thank the reviewer for helpful comments and Sahaana
B Arumugam, Anthony C Cruz, John R Ferdinand, Christian Geiger and
Arianne C Richard for critical reading of the manuscript.
NR 84
TC 8
Z9 8
U1 3
U2 26
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0019-2805
EI 1365-2567
J9 IMMUNOLOGY
JI Immunology
PD NOV
PY 2015
VL 146
IS 3
BP 349
EP 358
DI 10.1111/imm.12525
PG 10
WC Immunology
SC Immunology
GA CT6EX
UT WOS:000362906300001
PM 26301993
ER
PT J
AU Swindle, EJ
Brown, JM
Radinger, M
DeLeo, FR
Metcalfe, DD
AF Swindle, Emily J.
Brown, Jared M.
Radinger, Madeleine
DeLeo, Frank R.
Metcalfe, Dean D.
TI Interferon-gamma enhances both the anti-bacterial and the
pro-inflammatory response of human mast cells to Staphylococcus aureus
SO IMMUNOLOGY
LA English
DT Article
DE bacteria; innate immunity; beta(1) integrin; interferon-gamma; mast
cells
ID FC-EPSILON-RI; NECROSIS-FACTOR-ALPHA; ESCHERICHIA-COLI; IFN-GAMMA;
TNF-ALPHA; EPITHELIAL-CELLS; INNATE IMMUNITY; UP-REGULATION; IN-VITRO;
ACTIVATION
AB Human mast cells (huMCs) are involved in both innate and adaptive immune responses where they release mediators including amines, reactive oxygen species (ROS), eicosanoids and cytokines. We have reported that interferon- (IFN-gamma) enhances FcR-dependent ROS production. The aim of this study was to extend these observations by investigating the effect of IFN- on the biological responses of huMCs to Staphylococcus aureus. We found that exposure of huMCs to S.aureus generated intracellular and extracellular ROS, which were enhanced in the presence of IFN-gamma IFN-gamma also promoted bacteria killing, -hexosaminidase release and eicosanoid production. Interferon- similarly increased expression of mRNAs encoding CCL1 to CCL4, granulocyte-macrophage colony-stimulating factor (GM-CSF), tumour necrosis factor- and CXCL8 in S.aureus-stimulated huMCs. The ability of IFN- to increase CXCL8 and GM-CSF protein levels was confirmed by ELISA. Fibronectin or a beta(1) integrin blocking antibody completely abrogated IFN-gamma-dependent S.aureus binding and reduced S.aureus-dependent CXCL8 secretion. These data demonstrate that IFN-gamma primes huMCs for enhanced anti-bacterial and pro-inflammatory responses to S.aureus, partially mediated by beta(1) integrin.
C1 [Swindle, Emily J.] Univ Southampton, Southampton Univ Hosp, Fac Med, Acad Unit Clin & Expt Sci, Southampton SO16 6YD, Hants, England.
[Brown, Jared M.] Univ Colorado, Skaggs Sch Pharm & Pharmaceut Sci, Dept Pharmaceut Sci, Aurora, CO USA.
[Radinger, Madeleine] Univ Gothenburg, Krefting Res Ctr, Dept Internal Med & Clin Nutr, Gothenburg, Sweden.
[DeLeo, Frank R.] NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, Hamilton, MA USA.
[Metcalfe, Dean D.] NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA.
RP Swindle, EJ (reprint author), Univ Southampton, Southampton Univ Hosp, Fac Med, Acad Unit Clin & Expt Sci, Southampton SO16 6YD, Hants, England.
EM e.j.swindle@soton.ac.uk; dmetcalfe@niaid.nih.gov
FU Division of Intramural Research, NIAID/NIH
FX EJS designed and performed experiments, analysed data and composed the
manuscript. JB and MR provided some of the mast cell cultures and helped
with PCRs and ELISAs and edited the manuscript. FRD and DD critically
reviewed data and assisted in writing the manuscript. This work was
supported by the Division of Intramural Research, NIAID/NIH.
NR 41
TC 3
Z9 3
U1 0
U2 8
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0019-2805
EI 1365-2567
J9 IMMUNOLOGY
JI Immunology
PD NOV
PY 2015
VL 146
IS 3
BP 470
EP 485
DI 10.1111/imm.12524
PG 16
WC Immunology
SC Immunology
GA CT6EX
UT WOS:000362906300012
PM 26288256
ER
PT J
AU Jackson, JN
Haas, CJ
Fregly, BJ
AF Jackson, Jennifer N.
Haas, Chris J.
Fregly, Benjamin J.
TI Residual Elimination Algorithm Enhancements to Improve Foot Motion
Tracking During Forward Dynamic Simulations of Gait
SO JOURNAL OF BIOMECHANICAL ENGINEERING-TRANSACTIONS OF THE ASME
LA English
DT Article
DE gait; walking; residual elimination algorithm; optimization; forward
dynamic simulation; biomechanics
ID UNITED-STATES; HUMAN WALKING; ADULTS; REHABILITATION; OSTEOARTHRITIS;
POPULATION; PARAMETERS; FRAMEWORK; GRAVITY; IMPACT
AB Patient-specific gait optimizations capable of predicting post-treatment changes in joint motions and loads could improve treatment design for gait-related disorders. To maximize potential clinical utility, such optimizations should utilize full-body three-dimensional patient-specific musculoskeletal models, generate dynamically consistent gait motions that reproduce pretreatment marker measurements closely, and achieve accurate foot motion tracking to permit deformable foot-ground contact modeling. This study enhances an existing residual elimination algorithm (REA) Remy, C. D., and Thelen, D. G., 2009, "Optimal Estimation of Dynamically Consistent Kinematics and Kinetics for Forward Dynamic Simulation of Gait," ASME J. Biomech. Eng., 131(3), p. 031005) to achieve all three requirements within a single gait optimization framework. We investigated four primary enhancements to the original REA: (1) manual modification of tracked marker weights, (2) automatic modification of tracked joint acceleration curves, (3) automatic modification of algorithm feedback gains, and (4) automatic calibration of model joint and inertial parameter values. We evaluated the enhanced REA using a full-body three-dimensional dynamic skeletal model and movement data collected from a subject who performed four distinct gait patterns: walking, marching, running, and bounding. When all four enhancements were implemented together, the enhanced REA achieved dynamic consistency with lower marker tracking errors for all segments, especially the feet (mean root-mean-square (RMS) errors of 3.1 versus 18.4 mm), compared to the original REA. When the enhancements were implemented separately and in combinations, the most important one was automatic modification of tracked joint acceleration curves, while the least important enhancement was automatic modification of algorithm feedback gains. The enhanced REA provides a framework for future gait optimization studies that seek to predict subject-specific post-treatment gait patterns involving large changes in foot-ground contact patterns made possible through deformable foot-ground contact models.
C1 [Jackson, Jennifer N.; Fregly, Benjamin J.] Univ Florida, Dept Biomed Engn, Gainesville, FL 32611 USA.
[Jackson, Jennifer N.] NIH, Funct & Appl Biomech Sect, Dept Rehabil Med, Bethesda, MD 20892 USA.
[Haas, Chris J.] Univ Florida, Dept Appl Physiol & Kinesiol, Gainesville, FL 32611 USA.
[Fregly, Benjamin J.] Univ Florida, Dept Mech & Aerosp Engn, Gainesville, FL 32611 USA.
RP Fregly, BJ (reprint author), Univ Florida, Dept Mech & Aerosp Engn, Gainesville, FL 32611 USA.
EM fregly@ufl.edu
RI Fregly, Benjamin/O-6860-2016
OI Fregly, Benjamin/0000-0003-1166-4358
FU NSF [CBET 1052754, CBET 1159735]
FX This study was funded by NSF grant numbers CBET 1052754 and CBET
1159735.
NR 35
TC 0
Z9 0
U1 0
U2 2
PU ASME
PI NEW YORK
PA TWO PARK AVE, NEW YORK, NY 10016-5990 USA
SN 0148-0731
EI 1528-8951
J9 J BIOMECH ENG-T ASME
JI J. Biomech. Eng.-Trans. ASME
PD NOV
PY 2015
VL 137
IS 11
AR 111002
DI 10.1115/1.4031418
PG 8
WC Biophysics; Engineering, Biomedical
SC Biophysics; Engineering
GA CT5IT
UT WOS:000362842900002
PM 26299394
ER
PT J
AU Ladell, K
Hazenberg, MD
Fitch, M
Emson, C
Asgarian, BKMH
Mold, JE
Miller, C
Busch, R
Price, DA
Hellerstein, MK
McCune, JM
AF Ladell, Kristin
Hazenberg, Mette D.
Fitch, Mark
Emson, Claire
Asgarian, Bridget K. McEvoy-Hein
Mold, Jeff E.
Miller, Corey
Busch, Robert
Price, David A.
Hellerstein, Marc K.
McCune, Joseph M.
TI Continuous Antigenic Stimulation of DO11.10 TCR Transgenic Mice in the
Presence or Absence of IL-1 beta: Possible Implications for Mechanisms
of T Cell Depletion in HIV Disease
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID IMMUNE ACTIVATION; MICROBIAL TRANSLOCATION; ANTIRETROVIRAL THERAPY;
INFECTED PATIENTS; REGULATORY CELLS; IN-VIVO; CD4(+); IMMUNODEFICIENCY;
AIDS; PROLIFERATION
AB Untreated HIV disease is associated with chronic immune activation and CD4(+) T cell depletion. A variety of mechanisms have been invoked to account for CD4(+) T cell depletion in this setting, but the quantitative contributions of these proposed mechanisms over time remain unclear. We turned to the DO11.10 TCR transgenic mouse model, where OVA is recognized in the context of H-2(d), to explore the impact of chronic antigenic stimulation on CD4(+) T cell dynamics. To model dichotomous states of persistent Ag exposure in the presence or absence of proinflammatory stimulation, we administered OVA peptide to these mice on a continuous basis with or without the prototypic proinflammatory cytokine, IL-1 beta. In both cases, circulating Ag-specific CD4(+) T cells were depleted. However, in the absence of IL-1 beta, there was limited proliferation and effector/memory conversion of Ag-specific T cells, depletion of peripheral CD4(+) T cells in hematolymphoid organs, and systemic induction of regulatory Foxp3(+)CD4(+) T cells, as often observed in late-stage HIV disease. By contrast, when OVA peptide was administered in the presence of IL-1 beta, effector/memory phenotype T cells expanded and the typical symptoms of heightened immune activation were observed. Acknowledging the imperfect and incomplete relationship between Ag-stimulated DO11.10 TCR transgenic mice and HIV-infected humans, our data suggest that CD4(+) T cell depletion in the setting of HIV disease may reflect, at least in part, chronic Ag exposure in the absence of proinflammatory signals and/or appropriate APC functions.
C1 [Ladell, Kristin; Mold, Jeff E.; Miller, Corey; McCune, Joseph M.] Univ Calif San Francisco, Div Expt Med, San Francisco, CA 94110 USA.
[Hazenberg, Mette D.] Univ Med Ctr Utrecht, Dept Immunol, NL-3584 EA Utrecht, Netherlands.
[Fitch, Mark; Emson, Claire; Asgarian, Bridget K. McEvoy-Hein; Hellerstein, Marc K.] Univ Calif Berkeley, Dept Nutr Sci, Berkeley, CA 94720 USA.
[Emson, Claire; Hellerstein, Marc K.] KineMed Inc, Emeryville, CA 94608 USA.
[Busch, Robert] Univ Roehampton, Whitelands Coll, Dept Life Sci, London SW15 4JD, England.
[Price, David A.] Cardiff Univ, Sch Med, Inst Infect & Immun, Cardiff CF14 4XN, S Glam, Wales.
[Price, David A.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
RP McCune, JM (reprint author), Univ Calif San Francisco, Dept Med, Div Expt Med, 1001 Potrero Ave,Bldg 3,Room 601, San Francisco, CA 94110 USA.
EM ladellk@gmail.com; mike.mccune@ucsf.edu
RI Ladell, Kristin/C-8301-2013; Price, David/C-7876-2013
OI Ladell, Kristin/0000-0002-9856-2938; Price, David/0000-0001-9416-2737
FU National Institutes of Health [RO1 AI43866, U01 AI43641, R37 AI40312];
European Molecular Biology Organization [ALTF 254-2002]; Burroughs
Wellcome Fund Clinical Scientist Award in Translational Research;
National Institutes of Health Director's Pioneer Award, National
Institutes of Health Roadmap for Medical Research [DPI OD00329]; KineMed
Inc.; National Center for Research Resources, a component of the
National Institutes of Health [UL1 RR024131-01]; National Institutes of
Health Roadmap for Medical Research
FX This work was supported by National Institutes of Health Grant RO1
AI43866 (to M.K.H.); European Molecular Biology Organization Grant ALTF
254-2002 (to M.D.H.); National Institutes of Health Awards U01 AI43641
and R37 AI40312 (to J.M.M.); the Burroughs Wellcome Fund Clinical
Scientist Award in Translational Research (to J.M.M.); and the National
Institutes of Health Director's Pioneer Award (to J.M.M.), part of the
National Institutes of Health Roadmap for Medical Research, through
Grant DPI OD00329. Funding for the optimization of low-count techniques
by mass spectrometry was provided by KineMed Inc. D.A.P. is a Wellcome
Trust Senior Investigator. The Clinical and Translational Science
Institute Clinical Research Center at the University of California, San
Francisco was supported by Grant UL1 RR024131-01 from the National
Center for Research Resources, a component of the National Institutes of
Health, and the National Institutes of Health Roadmap for Medical
Research.
NR 39
TC 1
Z9 1
U1 0
U2 4
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
EI 1550-6606
J9 J IMMUNOL
JI J. Immunol.
PD NOV 1
PY 2015
VL 195
IS 9
BP 4096
EP 4105
DI 10.4049/jimmunol.1500799
PG 10
WC Immunology
SC Immunology
GA CT7BQ
UT WOS:000362968500007
PM 26416271
ER
PT J
AU Lu, Y
Cao, X
Zhang, XY
Kovalovsky, D
AF Lu, Ying
Cao, Xin
Zhang, Xianyu
Kovalovsky, Damian
TI PLZF Controls the Development of Fetal-Derived IL-17(+)V gamma 6(+)
gamma delta T Cells
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID TRANSCRIPTION FACTOR PLZF; ZINC-FINGER; CYCLE PROGRESSION; LINEAGE;
DIFFERENTIATION; INNATE; PROLIFERATION; PROGRAM; INTERLEUKIN-17;
INFLAMMATION
AB Expression of promyelocytic leukemia zinc finger (PLZF) protein directs the effector differentiation of invariant NKT (iNKT) cells and IL-4(+) gamma delta NKT cells. In this study, we show that PLZF is also required for the development and function of IL-17(+) gamma delta T cells. We observed that PLZF is expressed in fetal-derived invariant V gamma 5(+) and V gamma 6(+) gamma delta T cells, which secrete IFN-gamma and IL-17, respectively. PLZF deficiency specifically affected the effector differentiation of V gamma 6(+) cells, leading to reduced numbers of mature CD27(-)CD44(+) phenotype capable of secreting IL-17. Although PLZF was not required for V gamma 5(+) gamma delta T cells to develop, when these cells were reprogrammed into IL-17-secreting cells in Skint-1 mutant mice, they required PLZF for their effector maturation, similarly to V gamma 6(+) gamma delta T cells. The impaired effector differentiation of PLZF-deficient V gamma 6(+) gamma delta T cells was not due to increased apoptosis and it was related to reduced proliferation of immature CD27(+)CD44(-) V gamma 6(+) gamma delta T cells, which was required for their differentiation into mature CD27(-)CD44(+) IL-17-secreting cells. Thus, the present study identifies that PLZF function is not restricted to NKT or IL-4(+) T cells, but it also controls the development of IL-17(+) gamma delta T cells.
C1 [Lu, Ying; Cao, Xin; Zhang, Xianyu; Kovalovsky, Damian] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA.
RP Kovalovsky, D (reprint author), NCI, Expt Immunol Branch, NIH, 9000 Rockville Pike,Bldg 10-4B17, Bethesda, MD 20892 USA.
EM kovalovskyd@mail.nih.gov
FU National Institutes of Health intramural funds [1ZIABC011429]
FX This work was supported by National Institutes of Health intramural
funds (1ZIABC011429).
NR 40
TC 2
Z9 2
U1 1
U2 5
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
EI 1550-6606
J9 J IMMUNOL
JI J. Immunol.
PD NOV 1
PY 2015
VL 195
IS 9
BP 4273
EP 4281
DI 10.4049/jimmunol.1500939
PG 9
WC Immunology
SC Immunology
GA CT7BQ
UT WOS:000362968500025
PM 26408661
ER
PT J
AU Bardina, SV
Michlmayr, D
Hoffman, KW
Obara, CJ
Sum, J
Charo, IF
Lu, WY
Pletnev, AG
Lim, JK
AF Bardina, Susana V.
Michlmayr, Daniela
Hoffman, Kevin W.
Obara, Christopher J.
Sum, Janet
Charo, Israel F.
Lu, Wuyuan
Pletnev, Alexander G.
Lim, Jean K.
TI Differential Roles of Chemokines CCL2 and CCL7 in Monocytosis and
Leukocyte Migration during West Nile Virus Infection
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID CENTRAL-NERVOUS-SYSTEM; CD8(+) T-CELLS; NATIVE CHEMICAL LIGATION;
BONE-MARROW; MONONUCLEAR LEUKOCYTES; INFLAMMATORY MONOCYTES;
ALPHA/BETA-INTERFERON; UP-REGULATION; ENCEPHALITIS; RECEPTOR
AB West Nile virus (WNV) is a re-emerging pathogen and the leading cause of epidemic encephalitis in the United States. Inflammatory monocytes are a critical component of the cellular infiltrate found in the CNS duringWNVencephalitis, although the molecular cues involved in their migration are not fully understood. In mice, we previously showed that WNVinfection induces a CCR2-dependent monocytosis that precedes monocyte migration into the CNS. Currently, the relative contribution of the CCR2 ligands, chemokines CCL2 and CCL7, in directing monocyte mobilization and leukocyte migration into the CNS is unclear. In this study, we demonstrate that, although both CCL2 and CCL7 are required for efficient monocytosis and monocyte accumulation in the CNS, only CCL7 deficiency resulted in increased viral burden in the brain and enhanced mortality. The enhanced susceptibility in the absence of CCL7 was associated with the delayed migration of neutrophils and CD8(+) T cells into the CNS compared with WTor Ccl2(-/-) mice. To determine whether CCL7 reconstitution could therapeutically alter the survival outcome of WNV infection, we administered exogenous CCL7 i.v. to WNV-infected Ccl7(-/-) mice and observed a significant increase in monocytes and neutrophils, but not CD8(+) T cells, within the CNS, as well as an enhancement in survival compared with Ccl7(-/-) mice treated with a linear CCL7 control peptide. Our experiments suggest that CCL7 is an important protective signal involved in leukocyte trafficking during WNV infection, and it may have therapeutic potential for the treatment of acute viral infections of the CNS.
C1 [Bardina, Susana V.; Michlmayr, Daniela; Hoffman, Kevin W.; Sum, Janet; Lim, Jean K.] Icahn Sch Med Mt Sinai, Dept Microbiol, New York, NY 10029 USA.
[Obara, Christopher J.] NIAID, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA.
[Charo, Israel F.] Univ Calif San Francisco, Cardiovasc Res Inst, Dept Med, San Francisco, CA 94143 USA.
[Lu, Wuyuan] Univ Maryland, Sch Med, Inst Human Virol, Baltimore, MD 21201 USA.
[Lu, Wuyuan] Univ Maryland, Sch Med, Dept Biochem & Mol Biol, Baltimore, MD 21201 USA.
[Pletnev, Alexander G.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Lim, JK (reprint author), Icahn Sch Med Mt Sinai, Dept Microbiol, One Gustave L Levy Pl,Box 1124, New York, NY 10029 USA.
EM jean.lim@mssm.edu
RI Lu, Wuyuan/B-2268-2010
FU National Institute of Allergy and Infectious Diseases [R01AI108715,
F31AI110071]; Division of Intramural Research, National Institute of
Allergy and Infectious Diseases, National Institutes of Health; National
Institutes of Health Research Training Award [T32AI007647]
FX This work was supported by National Institute of Allergy and Infectious
Diseases Grant R01AI108715 and in part by the Division of Intramural
Research, National Institute of Allergy and Infectious Diseases,
National Institutes of Health. S.V.B. was supported in part by National
Institutes of Health Research Training Award T32AI007647 and National
Institute of Allergy and Infectious Diseases Grant F31AI110071.
NR 66
TC 8
Z9 8
U1 1
U2 9
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
EI 1550-6606
J9 J IMMUNOL
JI J. Immunol.
PD NOV 1
PY 2015
VL 195
IS 9
BP 4306
EP 4318
DI 10.4049/jimmunol.1500352
PG 13
WC Immunology
SC Immunology
GA CT7BQ
UT WOS:000362968500028
PM 26401006
ER
PT J
AU Hashimoto, M
Nasser, H
Bhuyan, F
Kuse, N
Satou, Y
Harada, S
Yoshimura, K
Sakuragi, J
Monde, K
Maeda, Y
Welbourn, S
Strebel, K
El-Wahab, EWA
Miyazaki, M
Hattori, S
Chutiwitoonchai, N
Hiyoshi, M
Oka, S
Takiguchi, M
Suzu, S
AF Hashimoto, Michihiro
Nasser, Hesham
Bhuyan, Farzana
Kuse, Nozomi
Satou, Yorifumi
Harada, Shigeyoshi
Yoshimura, Kazuhisa
Sakuragi, Jun-ichi
Monde, Kazuaki
Maeda, Yosuke
Welbourn, Sarah
Strebel, Klaus
El-Wahab, Ekram W. Abd
Miyazaki, Mitsue
Hattori, Shinichiro
Chutiwitoonchai, Nopporn
Hiyoshi, Masateru
Oka, Shinichi
Takiguchi, Masafumi
Suzu, Shinya
TI Fibrocytes Differ from Macrophages but Can Be Infected with HIV-1
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID CD4(+) T-CELLS; HEMATOPOIETIC PROGENITOR CELLS; ACTIVE ANTIRETROVIRAL
THERAPY; PERIPHERAL-BLOOD FIBROCYTES; VIRUS TYPE-1 VIREMIA; CIRCULATING
FIBROCYTES; BONE-MARROW; PULMONARY-FIBROSIS; CHEMOKINE RECEPTOR; VIRAL
RESERVOIRS
AB Fibrocytes (fibroblastic leukocytes) are recently identified as unique hematopoietic cells with features of both macrophages and fibroblasts. Fibrocytes are known to contribute to the remodeling or fibrosis of various injured tissues. However, their role in viral infection is not fully understood. In this study, we show that differentiated fibrocytes are phenotypically distinguishable from macrophages but can be infected with HIV-1. Importantly, fibrocytes exhibited persistently infected cell-like phenotypes, the degree of which was more apparent than macrophages. The infected fibrocytes produced replication-competent HIV-1, but expressed HIV-1 mRNA at low levels and strongly resisted HIV-1-induced cell death, which enabled them to support an extremely long-term HIV-1 production at low but steady levels. More importantly, our results suggested that fibrocytes were susceptible to HIV-1 regardless of their differentiation state, in contrast to the fact that monocytes become susceptible to HIV-1 after the differentiation into macrophages. Our findings indicate that fibrocytes are the previously unreported HIV-1 host cells, and they suggest the importance of considering fibrocytes as one of the long-lived persistently infected cells for curing HIV-1.
C1 [Hashimoto, Michihiro; Nasser, Hesham; Bhuyan, Farzana; Kuse, Nozomi; Satou, Yorifumi; El-Wahab, Ekram W. Abd; Miyazaki, Mitsue; Hattori, Shinichiro; Chutiwitoonchai, Nopporn; Hiyoshi, Masateru; Takiguchi, Masafumi; Suzu, Shinya] Kumamoto Univ, Ctr AIDS Res, Kumamoto 8600811, Japan.
[Hashimoto, Michihiro; Nasser, Hesham; Bhuyan, Farzana; Satou, Yorifumi; El-Wahab, Ekram W. Abd; Miyazaki, Mitsue; Takiguchi, Masafumi; Suzu, Shinya] Kumamoto Univ, Int Res Ctr Med Sci, Kumamoto 8600811, Japan.
[Harada, Shigeyoshi; Yoshimura, Kazuhisa] Natl Inst Infect Dis, AIDS Res Ctr, Tokyo 1628640, Japan.
[Sakuragi, Jun-ichi] Osaka Univ, Microbial Dis Res Inst, Suita, Osaka 5650871, Japan.
[Monde, Kazuaki; Maeda, Yosuke] Kumamoto Univ, Dept Med Virol, Kumamoto 8608556, Japan.
[Welbourn, Sarah; Strebel, Klaus] NIAID, NIH, Bethesda, MD 20892 USA.
[Oka, Shinichi] Natl Ctr Global Hlth & Med, AIDS Clin Ctr, Tokyo 1620052, Japan.
RP Suzu, S (reprint author), Kumamoto Univ, Int Res Ctr Med Sci, Ctr AIDS Res, Honjo 2-2-1, Kumamoto 8600811, Japan.
EM ssuzu06@kumamoto-u.ac.jp
RI Takiguchi, Masafumi/E-7468-2013;
OI Satou, Yorifumi/0000-0002-1495-7810
FU Takeda Science Foundation; Senshin Medical Research Foundation; Science
and Technology Development Fund, Egypt [6385]
FX This work was supported by the grants from the Takeda Science Foundation
and the Senshin Medical Research Foundation (to S.S.). E.W.A.E.-W. was
supported by Science and Technology Development Fund, Egypt Grant 6385.
NR 64
TC 1
Z9 1
U1 1
U2 4
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
EI 1550-6606
J9 J IMMUNOL
JI J. Immunol.
PD NOV 1
PY 2015
VL 195
IS 9
BP 4341
EP 4350
DI 10.4049/jimmunol.1500955
PG 10
WC Immunology
SC Immunology
GA CT7BQ
UT WOS:000362968500031
PM 26416279
ER
PT J
AU Singh, SP
Foley, JF
Zhang, HWH
Hurt, DE
Richards, JL
Smith, CS
Liao, F
Farber, JM
AF Singh, Satya P.
Foley, John F.
Zhang, Hongwei H.
Hurt, Darrell E.
Richards, Jennifer L.
Smith, Craig S.
Liao, Fang
Farber, Joshua M.
TI Selectivity in the Use of G(i/o) Proteins Is Determined by the DRF Motif
in CXCR6 and Is Cell-Type Specific
SO MOLECULAR PHARMACOLOGY
LA English
DT Article
ID BETA(2) ADRENERGIC-RECEPTOR; SITE-DIRECTED MUTAGENESIS; M1 MUSCARINIC
RECEPTOR; COUPLED RECEPTORS; CRYSTAL-STRUCTURE; T-CELLS;
BETA(2)-ADRENERGIC RECEPTOR; CONSTITUTIVE ACTIVATION; INTRACELLULAR
DOMAINS; CHEMOKINE RECEPTORS
AB CXCR6, the receptor for CXCL16, is expressed on multiple cell types and can be a coreceptor for human immunodeficiency virus 1. Except for CXCR6, all human chemokine receptors contain the (DRY3.51)-R-3.49-Y-3.50 sequence, and all but two contain A(3.53) at the cytoplasmic terminus of the third transmembrane helix (H3C), a region within class A G protein-coupled receptors that contacts G proteins. In CXCR6, H3C contains (DRFIV3.53)-R-3.49-F-3.50-I-3.51-V-3.52 at positions 126-130. We investigated the importance and interdependence of the canonical D126 and the noncanonical F128 and V130 in CXCR6 by mutating D126 to Y, F128 to Y, and V130 to A singly and in combination. For comparison, we mutated the analogous positions D142, Y144, and A146 to Y, F, and V, respectively, in CCR6, a related receptor containing the canonical sequences. Mutants were analyzed in both human embryonic kidney 293T and Jurkat E6-1 cells. Our data show that for CXCR6 and/or CCR6, mutations in H3C can affect both receptor signaling and chemokine binding; noncanonical H3C sequences are functionally linked, with dual changes mitigating the effects of single mutations; mutations in H3C that compromise receptor activity show selective defects in the use of individualG(i/o) proteins; and the effects of mutations in H3C on receptor function and selectivity in G(i/o) protein use can be cell-type specific. Our findings indicate that the ability of CXCR6 to make promiscuous use of the available G(i/o) proteins is exquisitely dependent on sequences within the H3C and suggest that the native sequence allows for preservation of this function across different cellular environments.
C1 [Singh, Satya P.; Foley, John F.; Zhang, Hongwei H.; Richards, Jennifer L.; Smith, Craig S.; Liao, Fang; Farber, Joshua M.] NIAID, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA.
[Hurt, Darrell E.] NIAID, Bioinformat & Sci IT Program, Off Technol Informat Syst, NIH, Bethesda, MD 20892 USA.
[Smith, Craig S.] NIH, Howard Hughes Med Inst, Res Scholars Program, Bethesda, MD 20892 USA.
RP Farber, JM (reprint author), NIAID, Lab Mol Immunol, NIH, Bldg 10,Rm 11N112,MSC 1886, Bethesda, MD 20892 USA.
EM jfarber@niaid.nih.gov
OI Foley, John/0000-0003-0395-5390
FU Intramural Research Program of the National Institute of Allergy and
Infectious Diseases, National Institutes of Health
FX This research was supported by the Intramural Research Program of the
National Institute of Allergy and Infectious Diseases, National
Institutes of Health.
NR 72
TC 1
Z9 1
U1 1
U2 3
PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA
SN 0026-895X
EI 1521-0111
J9 MOL PHARMACOL
JI Mol. Pharmacol.
PD NOV
PY 2015
VL 88
IS 5
BP 894
EP 910
DI 10.1124/mol.115.099960
PG 17
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA CT8AO
UT WOS:000363037400007
PM 26316539
ER
PT J
AU Capitanio, S
Nanni, C
Marini, C
Bonfiglioli, R
Martignani, C
Dib, B
Fuccio, C
Boriani, G
Picori, L
Boschi, S
Morbelli, S
Fanti, S
Sambuceti, G
AF Capitanio, Selene
Nanni, Cristina
Marini, Cecilia
Bonfiglioli, Rachele
Martignani, Cristian
Dib, Bassam
Fuccio, Chiara
Boriani, Giuseppe
Picori, Lorena
Boschi, Stefano
Morbelli, Silvia
Fanti, Stefano
Sambuceti, Gianmario
TI Heterogeneous response of cardiac sympathetic function to cardiac
resynchronization therapy in heart failure documented by
11[C]-hydroxy-ephedrine and PET/CT
SO NUCLEAR MEDICINE AND BIOLOGY
LA English
DT Article
DE Heart failure; Sympathetic innervation; Cardiac resynchronization
therapy; C-11-hydroxyephedrine; PET/CT
ID POSITRON-EMISSION-TOMOGRAPHY; DILATED CARDIOMYOPATHY; NERVOUS-SYSTEM;
NOREPINEPHRINE; CARVEDILOL; CARBON-11-META-HYDROXYEPHEDRINE;
HYPERTROPHY; INNERVATION; TRANSPORTER; RETENTION
AB Introduction: Cardiac resynchronization therapy (CRT) is an accepted treatment in patients with end-stage heart failure. PET permits the absolute quantification of global and regional homogeneity in cardiac sympathetic innervation. We evaluated the variation of cardiac adrenergic activity in patients with idiopathic heart failure (IHF) disease (NYHA III-IV) after CRT using C-11-hydroxyephedrine (HED) PET/CT.
Methods: Ten IHF patients (mean age = 68; range = 55-81; average left ventricular ejection fraction 26 +/- 4%) implanted with a resynchronization device underwent three HED PET/CT studies: PET 1 one week after inactive device implantation; PET 2, one week after PET 1 under stimulated rhythm; PET 3, at 3 months under active CRT. A dedicated software (PMOD 3.4 version) was used to estimate global and regional cardiac uptake of HED through 17 segment polar maps.
Results: At baseline, HED uptake was heterogeneously distributed throughout the left ventricle with a variation coefficient of 18 +/- 5%. This variable markedly decreased after three months CRT (12 +/- 5%, p < 0.01). Interestingly, subdividing the 170 myocardial segments (17 segments of each patient multiplied by the number of patients) into two groups, according to the median value of tracer uptake expressed as % of maximal myocardial uptake (76%), we observed a different behaviour depending on baseline innervation: HED uptake significantly increased only in segments with "impaired innervation" (SUV 2.61 +/- 0.92 at PET1 and 3.05 +/- 1.67 at three months, p<0.01).
Conclusion: As shown by HED PET/CT uptake and distribution, improvement in homogeneity of myocardial neuronal function reflected a selective improvement of tracer uptake in regions with more severe neuronal damage. Advances in Knowledge: These finding supported the presence of a myocardial regional variability in response of cardiac sympathetic system to CRT and a systemic response involving remote tissues with rich adrenergic innervation. Implication for patient care: This work might contribute to identify imaging parameters that could predict the response to CRT therapy. (C) 2015 Elsevier Inc. All rights reserved.
C1 [Capitanio, Selene; Dib, Bassam; Picori, Lorena; Morbelli, Silvia; Sambuceti, Gianmario] Univ Genoa, Dept Hlth Sci, IRCCS AOU San Martino IST, Nucl Med, I-16132 Genoa, Italy.
[Nanni, Cristina; Bonfiglioli, Rachele; Fuccio, Chiara; Boschi, Stefano; Fanti, Stefano] Univ Bologna, Azienda Osped Univ Bologna Policlin St Orsola Mal, Hematol Oncol & Lab Med Dept, Nucl Med, I-40126 Bologna, Italy.
[Marini, Cecilia] CNR, Inst Bioimages & Mol Physiol, Sect Genoa, I-20133 Milan, Italy.
[Martignani, Cristian; Boriani, Giuseppe] Univ Bologna, Azienda Osped Univ Bologna Policlin St Orsola Mal, Ist Cardiol, I-40126 Bologna, Italy.
RP Sambuceti, G (reprint author), Univ Genoa, IRCCS San Martino, Natl Canc Inst, Nucl Med, Lgo R Benzi 10, I-16132 Genoa, Italy.
EM Sambuceti@unige.it
RI Boriani, Giuseppe/A-4852-2015;
OI Boriani, Giuseppe/0000-0002-9820-4815; Sambuceti,
Gianmario/0000-0003-2979-6500
NR 35
TC 1
Z9 1
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0969-8051
EI 1872-9614
J9 NUCL MED BIOL
JI Nucl. Med. Biol.
PD NOV
PY 2015
VL 42
IS 11
BP 858
EP 863
DI 10.1016/j.nucmedbio.2015.07.002
PG 6
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA CT8NJ
UT WOS:000363073000007
PM 26239084
ER
PT J
AU Lee, JH
Kim, H
Yao, ZS
Lee, SJ
Szajek, LP
Grasso, L
Pastan, I
Paik, CH
AF Lee, Jae-Ho
Kim, Heejung
Yao, Zhengsheng
Lee, Sung-Jin
Szajek, Lawrence P.
Grasso, Luigi
Pastan, Ira
Paik, Chang H.
TI Tumor and organ uptake of Cu-64-labeled MORAb-009 (amatuximab), an
anti-mesothelin antibody, by PET imaging and biodistribution studies
SO NUCLEAR MEDICINE AND BIOLOGY
LA English
DT Article
DE Cu-64 labeling; NOTA; Mesothelin; Amatuximab; Antibody; Tumor targeting
ID IMMUNO-PET; MONOCLONAL-ANTIBODIES; EXPRESSING CANCERS; OVARIAN CANCERS;
RADIOIMMUNOTHERAPY
AB Objectives: To investigate the effect of the injection dose of MORAb-009 (amatuximab, an anti-mesothelin monoclonal antibody), the tumor size and the level of shed mesothelin on the uptake of the antibody in mesothelin-positive tumor and organs by biodistribution (BD) and positron emission tomography (PET) imaging studies.
Methods: 2-S-(4-Isothiocyanatobenzyl)-1,4,7-triazacydononane-1,4,7-triacetic acid (p-SCN-Bn-NOTA) was conjugated to amatuximab and labeled with (CuCl2)-Cu-64 in 0.25 M acetate buffer, pH 4.2. The resulting Cu-64-NOTA-amatuximab was purified with a PD 10 column. To investigate the dose effect or the effect of tumor size, the BD was performed in groups of nude mice (n = 5) with mesothelin-expressing A431/H9 tumors (range, 80-300 mm(3)) one day after iv injection of Cu-64-NOTA-amatuximab (10 mu Ci) containing a total amatuximab dose of 2, 30, or 60 mu g. The BD and PET imaging were also investigated 3, 24 and 48 h after injecting a total dose of 30 mu g (10 mu Ci for BD), and 2 or 60 mu g (300 mu Ci for PET), respectively.
Results: Comparing the results of the BDs from three different injection doses, the major difference was shown in the uptake (%ID/g) of the radiolabel in tumor, liver and blood. The tumor uptake and blood retention from 30 and 60 mu g doses were greater than those from 2 mu g dose, whereas the liver uptake was smaller. The BD studies also demonstrated a positive correlation between tumor size (or the level of shed mesothelin in blood) and liver uptake. However, there was a negative correlation between tumor size (or the shed mesothelin level) and tumor uptake and between tumor size and blood retention. These findings were confirmed by the PET imaging study, which clearly visualized the tumor uptake with the radiolabel concentrated in the tumor core and produced a tumor to liver ratio of 1.2 at 24 h post-injection with 60 mu g amatuximab, whereas the injection of 2 mu g amatuximab produced a tumor to liver ratio of 0.4 at 24 h post-injection.
Conclusion: Our studies using a nude mouse model of A431/H9 tumor demonstrated that the injection of a high amatuximab dose (30 to 60 mu g) could provide a beneficial effect in maximizing tumor uptake while maintaining minimum liver and spleen uptakes of the radiolabel, and in facilitating its penetration into the tumor core. Published by Elsevier Inc.
C1 [Lee, Jae-Ho; Kim, Heejung; Yao, Zhengsheng; Lee, Sung-Jin; Paik, Chang H.] NIH, Nucl Med, Radiol & Imaging Sci, Ctr Clin, Bethesda, MD 20892 USA.
[Szajek, Lawrence P.] NIH, Positron Emiss Tomog Dept, Ctr Clin, Bethesda, MD 20892 USA.
[Grasso, Luigi] Morphotek Inc, Exton, PA 19341 USA.
[Pastan, Ira] NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Lee, JH (reprint author), NIH, Nucl Med, Radiol & Imaging Sci, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA.
EM leejaeho@mail.nih.gov; cpaik@mail.nih.gov
FU intramural research program of Clinical Center, NIH
FX We thank Ms. Eden Dejene for her editorial assistance with this
manuscript. This research was supported by the intramural research
program of Clinical Center, NIH.
NR 28
TC 2
Z9 2
U1 2
U2 8
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0969-8051
EI 1872-9614
J9 NUCL MED BIOL
JI Nucl. Med. Biol.
PD NOV
PY 2015
VL 42
IS 11
BP 880
EP 886
DI 10.1016/j.nucmedbio.2015.07.008
PG 7
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA CT8NJ
UT WOS:000363073000010
PM 26307499
ER
PT J
AU Kitahara, CM
Linet, MS
Drozdovitch, V
Alexander, BH
Preston, DL
Simon, SL
Freedman, DM
Brill, AB
Miller, JS
Little, MP
Rajaraman, P
Doody, MM
AF Kitahara, Cari M.
Linet, Martha S.
Drozdovitch, Vladimir
Alexander, Bruce H.
Preston, Dale L.
Simon, Steven L.
Freedman, D. Michal
Brill, Aaron B.
Miller, Jeremy S.
Little, Mark P.
Rajaraman, Preetha
Doody, Michele M.
TI Cancer and circulatory disease risks in US radiologic technologists
associated with performing procedures involving radionuclides
SO OCCUPATIONAL AND ENVIRONMENTAL MEDICINE
LA English
DT Article
ID ATOMIC-BOMB SURVIVORS; IONIZING-RADIATION; NUCLEAR-MEDICINE;
UNITED-STATES; BRITISH RADIOLOGISTS; MORTALITY RISKS; EXPOSURE; WORKERS;
REGISTRY; HEALTH
AB Objectives The number of nuclear medicine procedures has increased substantially over the past several decades, with uncertain health risks to the medical workers who perform them. We estimated risks of incidence and mortality from cancer and circulatory disease associated with performing procedures involving the use of radionuclides.
Methods From a nationwide cohort of 90 955 US radiologic technologists who completed a mailed questionnaire during 1994-1998, 22 039 reported ever performing diagnostic radionuclide procedures, brachytherapy, radioactive iodine therapy, or other radionuclide therapy. We calculated multivariable-adjusted HRs and 95% CIs for incidence (through 2003-2005) and mortality (through 2008) associated with performing these procedures.
Results Ever (versus never) performing radionuclide procedures was not associated with risks for most end points examined. However, we observed increased risks for squamous cell carcinoma of the skin (HR=1.29, 95% CI 1.01 to 1.66) with ever performing diagnostic radionuclide procedures, for myocardial infarction incidence (HR=1.37, 95% CI 1.10 to 1.70), all-cause mortality (HR=1.10, 95% CI 1.00 to 1.20) and all-cancer mortality (HR=1.20, 95% CI 1.01 to 1.43) with ever performing brachytherapy, and for mortality from all causes (HR=1.14, 95% CI 1.01 to 1.30), breast cancer (HR=2.68, 95% CI 1.10 to 6.51), and myocardial infarction (HR=1.76, 95% CI 1.02 to 3.04) with ever performing other radionuclide therapy procedures (excluding brachytherapy and radioactive iodine); increasing risks were also observed with greater frequency of performing these procedures, particularly before 1980.
Conclusions The modest health risks among radiologic technologists performing procedures using radionuclides require further examination in studies with individual dose estimates, more detailed information regarding types of procedures performed and radionuclides used, and longer follow-up.
C1 [Kitahara, Cari M.; Linet, Martha S.; Drozdovitch, Vladimir; Simon, Steven L.; Freedman, D. Michal; Little, Mark P.; Rajaraman, Preetha; Doody, Michele M.] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Alexander, Bruce H.] Univ Minnesota, Sch Publ Hlth, Div Environm Hlth Sci, Minneapolis, MN USA.
[Preston, Dale L.] Hirosoft Int, Eureka, CA USA.
[Brill, Aaron B.] Vanderbilt Univ, Dept Radiol & Radiol Sci, Nashville, TN 37235 USA.
[Miller, Jeremy S.] Informat Management Syst Inc, Calverton, MD USA.
RP Kitahara, CM (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, 9609 Med Ctr Dr, Rockville, MD 20850 USA.
EM meinholdc@mail.nih.gov
RI Kitahara, Cari/R-8267-2016;
OI Little, Mark/0000-0003-0980-7567
FU Division of Cancer Epidemiology and Genetics, National Cancer Institute,
National Institutes of Health, Department of Health and Human Services,
USA
FX This research was funded by the intramural programme of the Division of
Cancer Epidemiology and Genetics, National Cancer Institute, National
Institutes of Health, Department of Health and Human Services, USA.
NR 33
TC 1
Z9 2
U1 4
U2 6
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 1351-0711
EI 1470-7926
J9 OCCUP ENVIRON MED
JI Occup. Environ. Med.
PD NOV
PY 2015
VL 72
IS 11
BP 770
EP 776
DI 10.1136/oemed-2015-102834
PG 7
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA CT6GA
UT WOS:000362909900004
PM 26220810
ER
PT J
AU Thoreson, CK
Chung, ST
Ricks, M
Reynolds, JC
Remaley, AT
Periwal, V
Li, Y
Sumner, AE
AF Thoreson, C. K.
Chung, S. T.
Ricks, M.
Reynolds, J. C.
Remaley, A. T.
Periwal, V.
Li, Y.
Sumner, A. E.
TI Biochemical and clinical deficiency is uncommon in African immigrants
despite a high prevalence of low vitamin D: the Africans in America
study
SO OSTEOPOROSIS INTERNATIONAL
LA English
DT Article
DE African immigrants; Bone mineral density; Parathyroid hormone; Vitamin D
ID BONE-MINERAL DENSITY; D-BINDING PROTEIN; 25-HYDROXYVITAMIN D; SECONDARY
HYPERPARATHYROIDISM; PARATHYROID-HORMONE; SEASONAL-VARIATION; D
INSUFFICIENCY; FRACTURE RISK; WHITE WOMEN; BLACK-WOMEN
AB African ancestry is associated with low vitamin D levels but high bone density. Fifty percent of African immigrants had low vitamin D levels, but < 10 % had evidence of deficiency. The value of providing vitamin D supplementation to African immigrants without evidence of deficiency needs to be determined.
Introduction The Endocrine Society and Institute of Medicine (IOM) have concluded from studies in largely white populations that 25(OH)D is necessary for bone health. However, their definition of vitamin D insufficiency differs. The Endocrine Society recommends a 25(OH)D threshold of < 30 ng/mL. The IOM uses a lower threshold of 25(OH)D of < 20 ng/mL. As African ancestry is associated with decreased 25(OH)D but increased bone mineral density (BMD), the applicability of these thresholds to Africans is unknown. Therefore, we examined in African immigrants the relationship of 25(OH)D to parathyroid hormone (PTH) and BMD.
Methods One hundred eighty-six African immigrants(69 % male, age 38 +/- 10 (mean +/- SD), range 20-64 years) living in metropolitan Washington, DC, were enrolled. BMD was determined from whole-body dual-energy X-ray absorptiometry (DXA) scans. Decreased BMD required T-scores a parts per thousand currency signa'1.0. The threshold for low 25(OH)D was the concentration of 25(OH)D at which PTH became suppressed. This is known as the inflection point. Biochemical deficiency required low 25(OH)D and PTH of > 65 pg/mL. Clinical deficiency required low 25(OH)D and T-scores a parts per thousand currency signa'1.0.
Results 25(OH)D < 30 and < 20 ng/mL occurred in 83 and 46 % of African immigrants, respectively. PTH inversely correlated with 25(OH)D (r = -0.31, P = 0.002). The inflection point occurred at a 25(OH)D concentration of 20 ng/mL. Biochemical and clinical deficiency occurred in only 8 and 3 % of immigrants, respectively.
Conclusion As PTH became suppressed at 25(OH)D of 20 ng/mL, the 25(OH)D < 20 ng/mL threshold for insufficiency may apply to African immigrants. However, similar to 50 % of African immigrants have 25(OH)D < 20 ng/mL, but only < 10 % had evidence of deficiency. The value of providing vitamin D supplementation to the large number of African immigrants with 25(OH)D < 20 ng/mL and no detectable evidence of deficiency needs to be determined.
C1 [Thoreson, C. K.; Chung, S. T.; Ricks, M.; Sumner, A. E.] NIDDK, Diabet Endocrinol & Obes Branch, NIH, Bethesda, MD 20892 USA.
[Reynolds, J. C.] NIH, Div Nucl Med, Radiol & Imaging Sci Dept, Ctr Clin, Bethesda, MD 20892 USA.
[Remaley, A. T.] NHLBI, Lipoprot Metab Sect, Cardiopulmonary Branch, NIH, Bethesda, MD 20892 USA.
[Periwal, V.; Li, Y.] NIDDK, Lab Biol Modeling, Computat Med Sect, NIH, Bethesda, MD 20892 USA.
RP Sumner, AE (reprint author), NIDDK, Diabet Endocrinol & Obes Branch, NIH, Bld 10-CRC,Rm 6-5940,MSC 1612,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM annes@intra.niddk.nih.gov
FU intramural program of National Institute of Diabetes and Digestive and
Kidney Diseases; Clinical Center; intramural program of National Heart,
Lung, and Blood Institute
FX Caroline K. Thoreson, Stephanie T. Chung, Madia Ricks, Vipul Periwal,
Yanjun Li, and Anne E. Sumner were supported by the intramural program
of National Institute of Diabetes and Digestive and Kidney Diseases.
James C. Reynolds was supported in the Clinical Center and Alan T.
Remaley was supported by the intramural program of National Heart, Lung,
and Blood Institute.
NR 39
TC 2
Z9 2
U1 1
U2 1
PU SPRINGER LONDON LTD
PI LONDON
PA 236 GRAYS INN RD, 6TH FLOOR, LONDON WC1X 8HL, ENGLAND
SN 0937-941X
EI 1433-2965
J9 OSTEOPOROSIS INT
JI Osteoporosis Int.
PD NOV
PY 2015
VL 26
IS 11
BP 2607
EP 2615
DI 10.1007/s00198-015-3169-z
PG 9
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA CT8CG
UT WOS:000363042000007
PM 26001560
ER
PT J
AU Kessler, RC
Stein, MB
Bliese, PD
Bromet, EJ
Chiu, WT
Cox, KL
Colpe, LJ
Fullerton, CS
Gilman, SE
Gruber, MJ
Heeringa, SG
Lewandowski-Romps, L
Millikan-Bell, A
Naifeh, JA
Nock, MK
Petukhova, MV
Rosellini, AJ
Sampson, NA
Schoenbaum, M
Zaslavsky, AM
Ursano, RJ
AF Kessler, R. C.
Stein, M. B.
Bliese, P. D.
Bromet, E. J.
Chiu, W. T.
Cox, K. L.
Colpe, L. J.
Fullerton, C. S.
Gilman, S. E.
Gruber, M. J.
Heeringa, S. G.
Lewandowski-Romps, L.
Millikan-Bell, A.
Naifeh, J. A.
Nock, M. K.
Petukhova, M. V.
Rosellini, A. J.
Sampson, N. A.
Schoenbaum, M.
Zaslavsky, A. M.
Ursano, R. J.
CA Army STARRS Collaborators
TI Occupational differences in US Army suicide rates
SO PSYCHOLOGICAL MEDICINE
LA English
DT Article
DE Army; Army STARRS; deployment; resiliency factors; suicide
ID HEALTH-CARE UTILIZATION; RISK-FACTORS; MENTAL-HEALTH; MILITARY
OCCUPATION; U.S. ARMY; RESILIENCE; DEPLOYMENT; SOLDIERS; WAR; STARRS
AB Background. Civilian suicide rates vary by occupation in ways related to occupational stress exposure. Comparable military research finds suicide rates elevated in combat arms occupations. However, no research has evaluated variation in this pattern by deployment history, the indicator of occupation stress widely considered responsible for the recent rise in the military suicide rate.
Method. The joint associations of Army occupation and deployment history in predicting suicides were analysed in an administrative dataset for the 729 337 male enlisted Regular Army soldiers in the US Army between 2004 and 2009.
Results. There were 496 suicides over the study period (22.4/100 000 person-years). Only two occupational categories, both in combat arms, had significantly elevated suicide rates: infantrymen (37.2/100 000 person-years) and combat engineers (38.2/100 000 person-years). However, the suicide rates in these two categories were significantly lower when currently deployed (30.6/100 000 person-years) than never deployed or previously deployed (41.2-39.1/100 000 person-years), whereas the suicide rate of other soldiers was significantly higher when currently deployed and previously deployed (20.2-22.4/100 000 person-years) than never deployed (14.5/100 000 person-years), resulting in the adjusted suicide rate of infantrymen and combat engineers being most elevated when never deployed [ odds ratio (OR) 2.9, 95% confidence interval (CI) 2.1-4.1], less so when previously deployed (OR 1.6, 95% CI 1.1-2.1), and not at all when currently deployed (OR 1.2, 95% CI 0.8-1.8). Adjustment for a differential 'healthy warrior effect' cannot explain this variation in the relative suicide rates of never-deployed infantrymen and combat engineers by deployment status.
Conclusions. Efforts are needed to elucidate the causal mechanisms underlying this interaction to guide preventive interventions for soldiers at high suicide risk.
C1 [Kessler, R. C.; Chiu, W. T.; Gruber, M. J.; Petukhova, M. V.; Rosellini, A. J.; Sampson, N. A.; Zaslavsky, A. M.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA.
[Stein, M. B.] Univ Calif San Diego, Dept Psychiat, La Jolla, CA 92093 USA.
[Stein, M. B.] Univ Calif San Diego, Dept Family & Prevent Med, La Jolla, CA 92093 USA.
[Stein, M. B.] VA San Diego Healthcare Syst, San Diego, CA USA.
[Bliese, P. D.] Univ S Carolina, Darla Moore Sch Business, Columbia, SC 29208 USA.
[Bromet, E. J.] SUNY Stony Brook, Dept Psychiat, Sch Med, Stony Brook, NY 11794 USA.
[Cox, K. L.; Millikan-Bell, A.] US Army Publ Hlth Command, Aberdeen Proving Ground, MD USA.
[Colpe, L. J.] NIMH, Div Serv & Intervent Res, Bethesda, MD 20892 USA.
[Fullerton, C. S.; Naifeh, J. A.; Ursano, R. J.] Uniformed Serv Univ Hlth Sci, Sch Med, Dept Psychiat, Ctr Study Traumat Stress, Bethesda, MD 20814 USA.
[Gilman, S. E.] Harvard Univ, Sch Publ Hlth, Dept Social & Behav Sci, Boston, MA 02115 USA.
[Gilman, S. E.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Heeringa, S. G.; Lewandowski-Romps, L.] Univ Michigan, Inst Social Res, Ann Arbor, MI USA.
[Nock, M. K.] Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA.
[Schoenbaum, M.] NIMH, Off Sci Policy Planning & Commun, Bethesda, MD 20892 USA.
RP Kessler, RC (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA.
EM kessler@hcp.med.harvard.edu
OI Gilman, Stephen/0000-0002-8331-6419
FU Department of the Army; US Department of Health and Human Services,
National Institutes of Health, National Institute of Mental Health
(NIH/NIMH) [U01MH 087981]; EPI-Q; Sanofi-Aventis Group; Walgreens Co.;
Janssen
FX Army STARRS was sponsored by the Department of the Army and funded under
cooperative agreement number U01MH 087981 with the US Department of
Health and Human Services, National Institutes of Health, National
Institute of Mental Health (NIH/NIMH). The contents are solely the
responsibility of the authors and do not necessarily represent the views
of the Department of Health and Human Services, the NIMH, the Department
of the Army or the DoD. As a cooperative agreement, scientists employed
by the NIMH (L. J. Colpe and M. Schoenbaum) and Army
liaisons/consultants [Col. Steven Cersovsky, M.D., M.P.H. (US Army
Public Health Command; USAPHC) and K. L. Cox, M.D., M.P.H. (USAPHC)]
collaborated to develop the study protocol and data collection
instruments, supervise data collection, interpret results and prepare
reports. Although a draft of this manuscript was submitted to the Army
and NIMH for review and comment prior to submission, this was with the
understanding that comments would be no more than advisory. R. C.
Kessler has been a consultant over the past 3 years for J & J Wellness &
Prevention, Inc., Lake Nona Institute, Ortho-McNeil Janssen Scientific
Affairs, Sanofi-Aventis Group, Shire US Inc. and Transcept
Pharmaceuticals Inc. and has had research support for his
epidemiological studies over this time period from EPI-Q, Sanofi-Aventis
Group, and Walgreens Co. R. C. Kessler owns stock in DataStat, Inc. M.
B. Stein has been a consultant for Healthcare Management Technologies
and had research support for pharmacological imaging studies from
Janssen. The remaining authors report nothing to disclose.
NR 48
TC 1
Z9 1
U1 3
U2 15
PU CAMBRIDGE UNIV PRESS
PI NEW YORK
PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA
SN 0033-2917
EI 1469-8978
J9 PSYCHOL MED
JI Psychol. Med.
PD NOV
PY 2015
VL 45
IS 15
BP 3293
EP 3304
DI 10.1017/S0033291715001294
PG 12
WC Psychology, Clinical; Psychiatry; Psychology
SC Psychology; Psychiatry
GA CT7HZ
UT WOS:000362986900015
PM 26190760
ER
PT J
AU Ballard, ED
Van Eck, K
Musci, RJ
Hart, SR
Storr, CL
Breslau, N
Wilcox, HC
AF Ballard, E. D.
Van Eck, K.
Musci, R. J.
Hart, S. R.
Storr, C. L.
Breslau, N.
Wilcox, H. C.
TI Latent classes of childhood trauma exposure predict the development of
behavioral health outcomes in adolescence and young adulthood
SO PSYCHOLOGICAL MEDICINE
LA English
DT Article
DE Childhood adverse experiences; latent class analysis; trauma; young
adulthood
ID POSTTRAUMATIC-STRESS-DISORDER; INTERNATIONAL DIAGNOSTIC INTERVIEW;
NATIONAL-COMORBIDITY-SURVEY; HOUSEHOLD DYSFUNCTION;
PSYCHIATRIC-DISORDERS; SUICIDE IDEATION; SUBSTANCE-ABUSE;
FAMILY-HISTORY; TOXIC STRESS; RISK-FACTORS
AB Background. To develop latent classes of exposure to traumatic experiences before the age of 13 years in an urban community sample and to use these latent classes to predict the development of negative behavioral outcomes in adolescence and young adulthood.
Method. A total of 1815 participants in an epidemiologically based, randomized field trial as children completed comprehensive psychiatric assessments as young adults. Reported experiences of nine traumatic experiences before age 13 years were used in a latent class analysis to create latent profiles of traumatic experiences. Latent classes were used to predict psychiatric outcomes at age 513 years, criminal convictions, physical health problems and traumatic experiences reported in young adulthood.
Results. Three latent classes of childhood traumatic experiences were supported by the data. One class (8% of sample), primarily female, was characterized by experiences of sexual assault and reported significantly higher rates of a range of psychiatric outcomes by young adulthood. Another class (8%), primarily male, was characterized by experiences of violence exposure and reported higher levels of antisocial personality disorder and post-traumatic stress. The final class (84%) reported low levels of childhood traumatic experiences. Parental psychopathology was related to membership in the sexual assault group.
Conclusions. Classes of childhood traumatic experiences predict specific psychiatric and behavioral outcomes in adolescence and young adulthood. The long-term adverse effects of childhood traumas are primarily concentrated in victims of sexual and non-sexual violence. Gender emerged as a key covariate in the classes of trauma exposure and outcomes.
C1 [Ballard, E. D.] NIMH, Expt & Pathophysiol Branch, Bethesda, MD 20892 USA.
[Van Eck, K.; Musci, R. J.; Storr, C. L.; Wilcox, H. C.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Mental Hlth, Baltimore, MD USA.
[Van Eck, K.] Johns Hopkins Univ, Sch Med, Div Pediat, Baltimore, MD USA.
[Hart, S. R.] Calif State Univ Chico, Dept Child Dev, Chico, CA 95929 USA.
[Storr, C. L.] Univ Maryland, Sch Nursing, Dept Family & Community Hlth, Baltimore, MD 21201 USA.
[Breslau, N.] Michigan State Univ, Dept Epidemiol & Biostat, E Lansing, MI 48824 USA.
[Wilcox, H. C.] Johns Hopkins Univ, Sch Med, Child & Adolescent Psychiat, Baltimore, MD USA.
RP Ballard, ED (reprint author), NIMH, Expt & Pathophysiol Branch, Bldg 10,CRC Room 7-3345,10 Ctr Dr,MSC 1282, Bethesda, MD 20892 USA.
EM Elizabeth.Ballard@nih.gov
FU National Institute of Health; National Institute of Mental Health
[MH090480, MH71395, MH 71395, MH 48802]; National Institute on Drug
Abuse [DA09897, DA04392, DA019805]
FX This work was supported by several National Institute of Health grants
over the span of the prospective study: National Institute of Mental
Health (MH090480, MH71395, MH 71395, MH 48802) and National Institute on
Drug Abuse (DA09897, DA04392, and DA019805).
NR 52
TC 4
Z9 4
U1 10
U2 30
PU CAMBRIDGE UNIV PRESS
PI NEW YORK
PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA
SN 0033-2917
EI 1469-8978
J9 PSYCHOL MED
JI Psychol. Med.
PD NOV
PY 2015
VL 45
IS 15
BP 3305
EP 3316
DI 10.1017/S0033291715001300
PG 12
WC Psychology, Clinical; Psychiatry; Psychology
SC Psychology; Psychiatry
GA CT7HZ
UT WOS:000362986900016
PM 26149665
ER
PT J
AU Dueck, AC
Mendoza, TR
Mitchell, SA
Reeve, BB
Castro, KM
Rogak, LJ
Atkinson, TM
Bennett, AV
Denicoff, AM
O'Mara, AM
Li, YL
Clauser, SB
Bryant, DM
Bearden, JD
Gillis, TA
Harness, JK
Siegel, RD
Paul, DB
Cleeland, CS
Schrag, D
Sloan, JA
Abernethy, AP
Bruner, DW
Minasian, LM
Basch, E
AF Dueck, Amylou C.
Mendoza, Tito R.
Mitchell, Sandra A.
Reeve, Bryce B.
Castro, Kathleen M.
Rogak, Lauren J.
Atkinson, Thomas M.
Bennett, Antonia V.
Denicoff, Andrea M.
O'Mara, Ann M.
Li, Yuelin
Clauser, Steven B.
Bryant, Donna M.
Bearden, James D., III
Gillis, Theresa A.
Harness, Jay K.
Siegel, Robert D.
Paul, Diane B.
Cleeland, Charles S.
Schrag, Deborah
Sloan, Jeff A.
Abernethy, Amy P.
Bruner, Deborah W.
Minasian, Lori M.
Basch, Ethan
CA Natl Canc Inst PRO-CTCAE Study Grp
TI Validity and Reliability of the US National Cancer Institute's
Patient-Reported Outcomes Version of the Common Terminology Criteria for
Adverse Events (PRO-CTCAE)
SO JAMA ONCOLOGY
LA English
DT Article
ID CLINICIAN; SYMPTOMS; CHEMOTHERAPY; INSTRUMENT; TOXICITIES; AGREEMENT;
ONCOLOGY; QLQ-C30; TRIALS
AB IMPORTANCE To integrate the patient perspective into adverse event reporting, the National Cancer Institute developed a patient-reported outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE).
OBJECTIVE To assess the construct validity, test-retest reliability, and responsiveness of PRO-CTCAE items.
DESIGN, SETTING, AND PARTICIPANTS A total of 975 adults with cancer undergoing outpatient chemotherapy and/or radiation therapy enrolled in this questionnaire-based study between January 2011 and February 2012. Eligible participants could read English and had no clinically significant cognitive impairment. They completed PRO-CTCAE items on tablet computers in clinic waiting rooms at 9 US cancer centers and community oncology practices at 2 visits 1 to 6 weeks apart. A subset completed PRO-CTCAE items during an additional visit 1 business day after the first visit.
MAIN OUTCOMES AND MEASURES Primary comparators were clinician-reported Eastern Cooperative Oncology Group Performance Status (ECOG PS) and the European Organisation for Research and Treatment of Cancer Core Quality of Life Questionnaire (QLQ-C30).
RESULTS A total of 940 of 975 (96.4%) and 852 of 940 (90.6%) participants completed PRO-CTCAE items at visits 1 and 2, respectively. At least 1 symptom was reported by 938 of 940 (99.8%) participants. Participants' median age was 59 years; 57.3% were female, 32.4% had a high school education or less, and 17.1% had an ECOG PS of 2 to 4. All PRO-CTCAE items had at least 1 correlation in the expected direction with a QLQ-C30 scale (111 of 124, P <.05 for all). Stronger correlations were seen between PRO-CTCAE items and conceptually related QLQ-C30 domains. Scores for 94 of 124 PRO-CTCAE items were higher in the ECOG PS 2 to 4 vs 0 to 1 group (58 of 124, P <.05 for all). Overall, 119 of 124 items met at least 1 construct validity criterion. Test-retest reliability was 0.7 or greater for 36 of 49 prespecified items (median [range] intraclass correlation coefficient, 0.76 [0.53-.96]). Correlations between PRO-CTCAE item changes and corresponding QLQ-C30 scale changes were statistically significant for 27 prespecified items (median [range] r = 0.43 [0.10-. 56]; all P <=.006).
CONCLUSIONS AND RELEVANCE Evidence demonstrates favorable validity, reliability, and responsiveness of PRO-CTCAE in a large, heterogeneous US sample of patients undergoing cancer treatment. Studies evaluating other measurement properties of PRO-CTCAE are under way to inform further development of PRO-CTCAE and its inclusion in cancer trials.
C1 [Dueck, Amylou C.] Mayo Clin, Dept Hlth Sci Res, Scottsdale, AZ USA.
[Mendoza, Tito R.; Cleeland, Charles S.] Univ Texas MD Anderson Canc Ctr, Dept Symptom Res, Houston, TX 77030 USA.
[Mitchell, Sandra A.; Castro, Kathleen M.; Clauser, Steven B.] NCI, Div Canc Control & Populat Sci, Rockville, MD USA.
[Reeve, Bryce B.; Bennett, Antonia V.; Basch, Ethan] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA.
[Rogak, Lauren J.; Basch, Ethan] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA.
[Atkinson, Thomas M.; Li, Yuelin] Mem Sloan Kettering Canc Ctr, Dept Psychiat & Behav Sci, 1275 York Ave, New York, NY 10021 USA.
[Denicoff, Andrea M.; Minasian, Lori M.] NCI, Div Canc Treatment & Diag, Rockville, MD USA.
[O'Mara, Ann M.] NCI, Canc Prevent Div, Rockville, MD USA.
[Bryant, Donna M.] Canc Program Our Lady Lake & Mary Bird Perkins, Dept Clin Res, Baton Rouge, LA USA.
[Bearden, James D., III] Gibbs Canc Ctr & Res Inst, Spartanburg, SC USA.
[Gillis, Theresa A.] Christiana Care Hlth Syst, Helen Graham Canc Ctr, Newark, DE USA.
[Gillis, Theresa A.] Christiana Care Hlth Syst, Res Inst, Newark, DE USA.
[Harness, Jay K.] St Joseph Hosp Orange, Ctr Canc Prevent & Treatment, Orange, CA USA.
[Siegel, Robert D.] Hartford Hosp, Helen & Harry Gray Canc Ctr, Hartford, CT 06115 USA.
[Schrag, Deborah] Dana Farber Canc Inst, Div Populat Sci, Boston, MA 02115 USA.
[Sloan, Jeff A.] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA.
[Abernethy, Amy P.] Duke Univ, Dept Med, Med Ctr, Durham, NC USA.
[Bruner, Deborah W.] Emory Univ, Nell Hodgson Woodruff Sch Nursing, Atlanta, GA 30322 USA.
RP Dueck, AC (reprint author), Mayo Clin, 13400 E Shea Blvd, Scottsdale, AZ 85259 USA.
EM dueck@mayo.edu
FU National Cancer Institute [HHSN261200800043C, HHSN261201000063C,
HHSN261200800001E]
FX This study was supported by contracts from the National Cancer
Institute: HHSN261200800043C, HHSN261201000063C, and HHSN261200800001E.
NR 31
TC 41
Z9 41
U1 0
U2 1
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 2374-2445
J9 JAMA ONCOL
JI JAMA Oncol.
PD NOV
PY 2015
VL 1
IS 8
BP 1051
EP 1059
DI 10.1001/jamaoncol.2015.2639
PG 10
WC Oncology
SC Oncology
GA DW5IO
UT WOS:000383677700008
PM 26270597
ER
PT J
AU Landgren, O
Shim, YK
Michalek, J
Costello, R
Burton, D
Ketchum, N
Calvo, KR
Caporaso, N
Raveche, E
Middleton, D
Marti, G
Vogt, RF
AF Landgren, Ola
Shim, Youn K.
Michalek, Joel
Costello, Rene
Burton, Debra
Ketchum, Norma
Calvo, Katherine R.
Caporaso, Neil
Raveche, Elizabeth
Middleton, Dan
Marti, Gerald
Vogt, Robert F., Jr.
TI Agent Orange Exposure and Monoclonal Gammopathy of Undetermined
Significance An Operation Ranch Hand Veteran Cohort Study
SO JAMA ONCOLOGY
LA English
DT Article
ID EARLY TREATMENT STRATEGIES; PRECEDES MULTIPLE-MYELOMA;
AGRICULTURAL-WORKERS; BIOLOGICAL INSIGHTS; PESTICIDE EXPOSURE;
SIGNIFICANCE MGUS; CANCER INCIDENCE; UNITED-STATES; LIGHT-CHAINS; IOWA
FARMERS
AB IMPORTANCE Multiple myeloma has been classified as exhibiting "limited or suggestive evidence" of an association with exposure to herbicides in Vietnam War veterans. Occupational studies have shown that other pesticides (ie, insecticides, herbicides, fungicides) are associated with excess risk of multiple myeloma and its precursor state, monoclonal gammopathy of undetermined significance (MGUS); however, to our knowledge, no studies have uncovered such an association in Vietnam War veterans.
OBJECTIVE To examine the relationship between MGUS and exposure to Agent Orange, including its contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), in Vietnam War veterans.
DESIGN, SETTING, AND PARTICIPANTS This was a prospective cohort study conducted in 2013 to 2014, testing for MGUS in serum specimens collected and stored in 2002 by the Air Force Health Study (AFHS). The relevant exposure data collected by the AFHS was also used. We tested all specimens in 2013 without knowledge of the exposure status. The AFHS included former US Air Force personnel who participated in Operation Ranch Hand (Ranch Hand veterans) and other US Air Force personnel who had similar duties in Southeast Asia during the same time period (1962 to 1971) but were not involved in herbicide spray missions (comparison veterans). Agent Orange was used by the US Air Force personnel who conducted aerial spray missions of herbicides (Operation Ranch Hand) in Vietnam from 1962 to 1971. We included 479 Ranch Hand veterans and 479 comparison veterans who participated in the 2002 follow-up examination of AFHS.
EXPOSURES Agent Orange and TCDD. Serum TCDD levels were measured in 1987, 1992, 1997, and 2002.
MAIN OUTCOMES AND MEASURES Risk of MGUS measured by prevalence, odds ratios (ORs), and 95% CIs.
RESULTS The 479 Ranch Hand veterans and 479 comparison veterans had similar demographic and lifestyle characteristics and medical histories. The crude prevalence of overall MGUS was 7.1%(34 of 479) in Ranch Hand veterans and 3.1% (15 of 479) in comparison veterans. This translated into a 2.4-fold increased risk for MGUS in Ranch Hand veterans than comparison veterans after adjusting for age, race, BMI in 2002, and the change in BMI between 2002 and the time of blood draw for TCDD measurement (adjusted OR, 2.37; 95% CI, 1.27-4.44; P =.007).
CONCLUSIONS AND RELEVANCE Operation Ranch Hand veterans have a significantly increased risk of MGUS, supporting an association between Agent Orange exposure and multiple myeloma.
C1 [Landgren, Ola; Costello, Rene; Burton, Debra; Caporaso, Neil] NCI, NIH, Bethesda, MD 20892 USA.
[Landgren, Ola] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
[Shim, Youn K.; Middleton, Dan] Agcy Tox Subst & Dis Registry, Atlanta, GA USA.
[Michalek, Joel; Ketchum, Norma] Univ Texas Hlth Sci Ctr San Antonio, Dept Epidemiol & Biostat, San Antonio, TX 78229 USA.
[Calvo, Katherine R.] NIH, Ctr Clin, Bethesda, MD 20892 USA.
[Raveche, Elizabeth] Rutgers New Jersey Med Sch, Dept Pathol & Lab Med, Newark, NJ USA.
[Marti, Gerald] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA.
[Vogt, Robert F., Jr.] Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Atlanta, GA USA.
RP Landgren, O (reprint author), Mem Sloan Kettering Canc Ctr, Myeloma Serv, 1275 York Ave, New York, NY 10065 USA.
EM landgrec@mskcc.org
FU Intramural Program at the Agency for Toxic Substances and Disease
Registry; Intramural Program at the National Cancer Institute; Air Force
Health Study (AFHS) Assets Research Program at the Institute of Medicine
FX This study was supported by the Intramural Program at the Agency for
Toxic Substances and Disease Registry, the Intramural Program at the
National Cancer Institute, and the Air Force Health Study (AFHS) Assets
Research Program at the Institute of Medicine through an award to the
Centers for Disease Control and Prevention (CDC) Foundation.
NR 50
TC 4
Z9 5
U1 0
U2 1
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 2374-2445
J9 JAMA ONCOL
JI JAMA Oncol.
PD NOV
PY 2015
VL 1
IS 8
BP 1061
EP 1068
DI 10.1001/jamaoncol.2015.2938
PG 8
WC Oncology
SC Oncology
GA DW5IO
UT WOS:000383677700010
PM 26335650
ER
PT J
AU Heery, CR
Ibrahim, NK
Arlen, PM
Mohebtash, M
Murray, JL
Koenig, K
Madan, RA
McMahon, S
Marte, JL
Steinberg, SM
Donahue, RN
Grenga, I
Jochems, C
Farsaci, B
Folio, LR
Schlom, J
Gulley, JL
AF Heery, Christopher R.
Ibrahim, Nuhad K.
Arlen, Philip M.
Mohebtash, Mahsa
Murray, James L.
Koenig, Kimberly
Madan, Ravi A.
McMahon, Sheri
Marte, Jennifer L.
Steinberg, Seth M.
Donahue, Renee N.
Grenga, Italia
Jochems, Caroline
Farsaci, Benedetto
Folio, Les R.
Schlom, Jeffrey
Gulley, James L.
TI Docetaxel Alone or in Combination With a Therapeutic Cancer Vaccine
(PANVAC) in Patients With Metastatic Breast Cancer A Randomized Clinical
Trial
SO JAMA ONCOLOGY
LA English
DT Article
ID RESISTANT PROSTATE-CANCER; COLONY-STIMULATING FACTOR; POXVIRAL-BASED
VACCINE; T-CELL RESPONSES; SIPULEUCEL-T; PHASE-II; IMMUNOTHERAPY; CEA;
CARCINOMA; CHEMOTHERAPY
AB IMPORTANCE Previous phase 1 and 2 trials of PANVAC, a poxviral-based cancer vaccine, have suggested clinical efficacy in some patients with breast, ovarian, and colorectal cancer and have shown evidence of immunologic activity. Preclinical data have shown that docetaxel can modify tumor phenotype, making tumor cells more amenable to T cell-mediated killing.
OBJECTIVE The goal of this study was to determine if the treatment combination of docetaxel and PANVAC improves clinical outcomes in patients with metastatic breast cancer compared with docetaxel treatment alone.
DESIGN, SETTING, AND PARTICIPANTS Between May 2006 and February 2012, this open-label, phase 2 randomized clinical trial enrolled 48 patients with metastatic breast cancer of all subtypes, without limitation on other lines of previous therapy, to receive treatment with either docetaxel with PANVAC (arm A) or docetaxel alone (arm B). Final clinical data were collected on September 16, 2013. All patients were treated at either the National Cancer Institute or the Department of Breast Medical Oncology, MD Anderson Cancer Center.
MAIN OUTCOMES AND MEASURES The primary end point was progression-free survival (PFS), using a phase 2.5 statistical design, with the intent of identifying a trend toward benefit (defined as 1-sided P <= .10) to guide a larger trial design. Secondary end points included safety and immunologic correlative studies.
RESULTS Forty-eight participants were enrolled: 25 were randomized to the combination treatment arm A, and 23 to arm B. No patient remained in the study at the time of the final analysis. Patient and tumor characteristics were well matched. Analysis of adverse events in both treatment arms demonstrated very little difference between the 2 groups. In the combination treatment arm (arm A), statistically significant increases were noted in the frequency of grades 1 and 2 edema (P = .02, likely related to greater median number of docetaxel cycles) and injection-site reactions (P < .001). In the final data analysis, median PFS was 7.9 months in arm A vs 3.9 months in arm B (hazard ratio, 0.65 [95% CI, 0.34-1.14]; P = .09).
CONCLUSIONS AND RELEVANCE The results suggest that the combination of PANVAC with docetaxel in metastatic breast cancer may provide a clinical benefit. This study was hypothesis generating and provides both rationale and statistical assumptions for a larger definitive randomized study.
C1 [Madan, Ravi A.; McMahon, Sheri; Marte, Jennifer L.; Gulley, James L.] NCI, Genitourinary Malignancies Branch, Ctr Canc Res, NIH, 10 Ctr Dr,Room 12N226, Bethesda, MD 20892 USA.
[Heery, Christopher R.; Arlen, Philip M.; Mohebtash, Mahsa; Donahue, Renee N.; Grenga, Italia; Jochems, Caroline; Farsaci, Benedetto; Schlom, Jeffrey] NCI, Lab Tumor Immunol & Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Ibrahim, Nuhad K.; Murray, James L.; Koenig, Kimberly] Univ Texas MD Anderson Canc Ctr, Dept Breast Med Oncol, Div Canc Med, Houston, TX 77030 USA.
[Steinberg, Seth M.] NCI, Biostat & Data Management Sect, Off Clin Director, Ctr Canc Res, Bethesda, MD 20892 USA.
[Folio, Les R.] NCI, Radiol & Imaging Serv, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Gulley, JL (reprint author), NCI, Genitourinary Malignancies Branch, Ctr Canc Res, NIH, 10 Ctr Dr,Room 12N226, Bethesda, MD 20892 USA.
EM gulleyj@mail.nih.gov
FU Intramural Research Program of the Center for Cancer Research, National
Cancer Institute, National Institutes of Health
FX This research was supported by the Intramural Research Program of the
Center for Cancer Research, National Cancer Institute, National
Institutes of Health.
NR 28
TC 12
Z9 12
U1 0
U2 4
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA
SN 2374-2445
J9 JAMA ONCOL
JI JAMA Oncol.
PD NOV
PY 2015
VL 1
IS 8
BP 1087
EP 1095
DI 10.1001/jamaoncol.2015.2736
PG 9
WC Oncology
SC Oncology
GA DW5IO
UT WOS:000383677700014
PM 26291768
ER
PT J
AU Keutgen, XM
Glanville, J
Kerkar, S
Kebebew, E
AF Keutgen, Xavier M.
Glanville, Joanne
Kerkar, Sid
Kebebew, Electron
TI Serous Cystadenoma of the Pancreas Causing Obstructive Jaundice in a
Patient with Von Hippel-Lindau Disease
SO JOURNAL OF THE PANCREAS
LA English
DT Article
DE von Hippel-Lindau Disease; Cystadenoma, Serous
ID COMMON BILE-DUCT; INVOLVEMENT; LESIONS
AB Context Cystic lesions of the pancreas are a common finding in patients with von Hippel-Lindau disease (vHL). However, only twelve cases of pancreatic cystic lesions causing obstructive jaundice have been reported in vHL patients. Case report Herein we report the rare case of a massive serous cystadenoma of the pancreatic head causing obstructive jaundice in a fifty-one-year-old female with vHL. Preoperative biliary decompression was achieved via ERCP and stent placement. Since the whole pancreas showed cystic degenerations, a total pancreatectomy was performed. Final histopathology showed diffuse compression of the distal intrapancreatic common bile duct but no evidence of malignancy. Conclusion To our knowledge this is only the second case report of a total pancreatectomy performed in a patient with vHL for biliary obstruction caused by a serous cystadenoma of the pancreas. Surgical intervention in this rare scenario should be recommended, because of the inability to rule out malignancy and the necessity to address the biliary obstruction.
C1 [Keutgen, Xavier M.; Glanville, Joanne; Kebebew, Electron] NCI, Endocrine Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Kerkar, Sid] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA.
RP Keutgen, XM (reprint author), NCI, EOB, NIH, 10 Ctr Dr,3W-5840, Bethesda, MD 20892 USA.
EM xavier.keutgen@nih.gov
NR 13
TC 0
Z9 0
U1 0
U2 0
PU E S BURIONI RICERCHE BIBLIOGRAFICHE
PI GENOVA
PA CORSO FIRENZE 41-2, GENOVA, 16136, ITALY
SN 1590-8577
J9 J PANCREAS
JI J. Pancreas
PD NOV
PY 2015
VL 16
IS 6
BP 616
EP 618
PG 3
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA DY6KS
UT WOS:000385225400017
ER
PT J
AU Mensch, BS
Gorbach, PM
Kelly, C
Kiepiela, P
Gomez, K
Ramjee, G
Ganesh, S
Morar, N
Soto-Torres, L
Parikh, UM
AF Mensch, Barbara S.
Gorbach, Pamina M.
Kelly, Cliff
Kiepiela, Photini
Gomez, Kailazarid
Ramjee, Gita
Ganesh, Shayhana
Morar, Neetha
Soto-Torres, Lydia
Parikh, Urvi M.
TI Characteristics Associated with HIV Drug Resistance Among Women
Screening for an HIV Prevention Trial in KwaZulu-Natal, South Africa
SO AIDS AND BEHAVIOR
LA English
DT Article
DE HIV drug resistance; KwaZulu-Natal; HIV-positive women screening for a
prevention trial
ID SUB-SAHARAN AFRICA; ANTIRETROVIRAL THERAPY; PREEXPOSURE PROPHYLAXIS;
SURVEILLANCE; TRANSMISSION; INFECTION
AB While the expansion of antiretroviral therapy (ART) in sub-Saharan Africa has reduced morbidity and mortality from HIV/AIDS, it has increased concern about drug resistance. The Microbicide Trials Network 009 study assessed the prevalence of drug-resistance mutations among women at clinical sites in Durban, South Africa who tested seropositive for HIV-1 at screening for the VOICE trial. The objective of this paper was to identify characteristics and behaviors associated with drug resistance. Factors found to be significantly associated with increased resistance were high perceived risk of getting HIV and prior participation in a microbicide trial, a likely proxy for familiarity with the health care system. Two factors were found to be significantly associated with reduced resistance: having a primary sex partner and testing negative for HIV in the past year. Other variables hypothesized to be important in identifying women with resistant virus, including partner or friend on ART who shared with the participant and being given antiretrovirals during pregnancy or labor, or the proxy variable-number of times given birth in a health facility-were not significantly associated. The small number of participants with resistant virus and the probable underreporting of sensitive behaviors likely affected our ability to construct a comprehensive profile of the type of HIV-positive women at greatest risk of developing resistance mutations.
C1 [Mensch, Barbara S.] Populat Council, New York, NY 10017 USA.
[Gorbach, Pamina M.] Univ Calif Los Angeles, Fielding Sch Publ Hlth, Dept Epidemiol, Los Angeles, CA USA.
[Kelly, Cliff] Fred Hutchinson Canc Res Ctr, Stat Ctr HIV AIDS Res & Prevent, Seattle, WA 98104 USA.
[Kiepiela, Photini; Ramjee, Gita; Ganesh, Shayhana; Morar, Neetha] South African Med Res Council, HIV Prevent Res Unit, Durban, South Africa.
[Gomez, Kailazarid] FHI 360, Durham, NC USA.
[Soto-Torres, Lydia] NIAID, Div Aids, NIH, Bethesda, MD 20892 USA.
[Parikh, Urvi M.] Univ Pittsburgh, Sch Med, Dept Med, Div Infect Dis, Pittsburgh, PA 15213 USA.
RP Mensch, BS (reprint author), Populat Council, One Dag Hammarskjold Plaza, New York, NY 10017 USA.
EM bmensch@popcouncil.org
FU National Institute of Allergy and Infectious Diseases [UM1AI068633,
UM1AI068615, UM1AI106707]; Eunice Kennedy Shriver National Institute of
Child Health and Human Development; National Institute of Mental Health
FX We gratefully acknowledge the study participants, the communities and
all the sites at which the study took place, health service providers,
the South African Medical Research Council Institutional Review Board,
and all of the MTN-009 Study Team including the clinical research site
leaders Sarita Naidoo, Zakir Gaffoor, Marwah Jenneker, Zola Msiska,
Arendevi Pather, Charlene Harichund, Sharika Gappoo, Jessica Philip,
Nicola Coumi, Samantha Sukhdeo, Yuki Sookrajh, Leith Kwaan, Vijayanand
Guddera and Brodie Daniels. We acknowledge the contributions of Benoit
Masse, Paul Edelfsen and Karen Patterson from the Statistical Center for
HIV/AIDS Research & Prevention (SCHARP). We also thank Stan Mierzwa and
the Population Council IT team that designed and implemented the ACASI
software, and Beth Galaska-Burzuk and Judy Jones from the MTN Core for
their support during protocol development. The Microbicide Trials
Network is funded by the National Institute of Allergy and Infectious
Diseases (UM1AI068633, UM1AI068615, UM1AI106707), with co-funding from
the Eunice Kennedy Shriver National Institute of Child Health and Human
Development and the National Institute of Mental Health, all components
of the U.S. National Institutes of Health.
NR 26
TC 0
Z9 0
U1 0
U2 2
PU SPRINGER/PLENUM PUBLISHERS
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1090-7165
EI 1573-3254
J9 AIDS BEHAV
JI AIDS Behav.
PD NOV
PY 2015
VL 19
IS 11
BP 2076
EP 2086
DI 10.1007/s10461-015-1056-4
PG 11
WC Public, Environmental & Occupational Health; Social Sciences, Biomedical
SC Public, Environmental & Occupational Health; Biomedical Social Sciences
GA CT2TQ
UT WOS:000362657300013
PM 25931240
ER
PT J
AU Marathe, S
Liu, S
Brai, E
Kaczarowski, M
Alberi, L
AF Marathe, S.
Liu, S.
Brai, E.
Kaczarowski, M.
Alberi, L.
TI Notch signaling in response to excitotoxicity induces neurodegeneration
via erroneous cell cycle reentry
SO CELL DEATH AND DIFFERENTIATION
LA English
DT Article
ID NEURAL STEM-CELLS; NEURONAL DEATH; ALZHEIMERS-DISEASE; ISCHEMIC-STROKE;
POSTMITOTIC NEURONS; NERVOUS-SYSTEM; GENE KNOCKOUT; ADULT BRAIN;
MOUSE-BRAIN; PATHWAY
AB Neurological disorders such as Alzheimer's disease, stroke and epilepsy are currently marred by the lack of effective treatments to prevent neuronal death. Erroneous cell cycle reentry (CCR) is hypothesized to have a causative role in neurodegeneration. We show that forcing S-phase reentry in cultured hippocampal neurons is sufficient to induce neurodegeneration. We found that kainic-acid treatment in vivo induces erroneous CCR and neuronal death through a Notch-dependent mechanism. Ablating Notch signaling in neurons provides neuroprotection against kainic acid-induced neuronal death. We further show that kainic-acid treatment activates Notch signaling, which increases the bioavailability of CyclinD1 through Akt/GSK3 beta pathway, leading to aberrant CCR via activation of CyclinD1-Rb-E2F1 axis. In addition, pharmacological blockade of this pathway at critical steps is sufficient to confer resistance to kainic acid-induced neurotoxicity in mice. Taken together, our results demonstrate that excitotoxicity leads to neuronal death in a Notch-dependent manner through erroneous CCR.
C1 [Marathe, S.; Brai, E.; Kaczarowski, M.; Alberi, L.] Univ Fribourg, Inst Anat, Dept Med, CH-1700 Fribourg, Switzerland.
[Liu, S.] NINDS, Receptor Biol Sect, NIH, Bethesda, MD 20892 USA.
RP Alberi, L (reprint author), Univ Fribourg, Inst Anat, Dept Med, Route Gockel 1, CH-1700 Fribourg, Switzerland.
EM lavinia.alberi@unifr.ch
FU Swiss National Foundation; Swiss Heart Association; Synapsis Foundation
FX This work was supported by funds from the Swiss National Foundation,
Swiss Heart Association and Synapsis Foundation. We would like to thank
Dr. Nicholas Gaiano for his continuous support to our lab. We thank T
Honjo for sharing the RBPJKfloxed/floxed mouse line. F
Calegari and B Artegiani for providing us the 4D construct. We are
thankful to Dr. Solinas for providing the p110 gamma antibody. We thank
P Clarke and J Puyal for their helpful scientific input on the study.
NR 54
TC 6
Z9 6
U1 3
U2 11
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1350-9047
EI 1476-5403
J9 CELL DEATH DIFFER
JI Cell Death Differ.
PD NOV
PY 2015
VL 22
IS 11
BP 1775
EP 1784
DI 10.1038/cdd.2015.23
PG 10
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA CS9US
UT WOS:000362438500005
PM 25822340
ER
PT J
AU Cohen, JS
Levy, HP
Sloan, J
Dariotis, J
Biesecker, BB
AF Cohen, J. S.
Levy, H. P.
Sloan, J.
Dariotis, J.
Biesecker, B. B.
TI Depression among adults with neurofibromatosis type 1: prevalence and
impact on quality of life
SO CLINICAL GENETICS
LA English
DT Article
DE depression; neurofibromatosis; psychosocial burden; quality of life
ID CHILDREN; ADOLESCENTS
AB Neurofibromatosis type 1 (NF1) carries a significant psychosocial burden for affected individuals. The objective of this study was to measure the prevalence of depressive symptoms among a large sample of adults with NF1 and to quantify the impact of depressive symptoms on quality of life (QoL). This cross-sectional study used an Internet-based questionnaire to collect data from 498 adults who self-reported as having NF1. Using the Center for Epidemiologic Studies Depression (CESD) scale, 55% of all participants (61% of females and 43% of males) scored above 16, indicating a high likelihood of clinical depression. In a multivariate regression model controlling for demographics and potential confounders, depressive symptoms accounted for 32% of the variance in QoL as measured by the Quality of Life Index. This study is the largest to date and found the highest prevalence of depression compared to prior studies. Our data provide more compelling evidence that individuals with NF1 are at increased risk for psychiatric morbidity and suggest that this population should be routinely screened for depression. Because depression was found to be strongly associated with QoL and accounted for nearly one-third of the variance in QoL, it is likely that effectively treating depression may significantly enhance QoL for individuals with NF1.
C1 [Cohen, J. S.] Kennedy Krieger Inst, Dept Neurol & Dev Med, Baltimore, MD 21205 USA.
[Levy, H. P.] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD USA.
[Levy, H. P.] Johns Hopkins Univ, Sch Med, Div Gen Internal Med, Baltimore, MD USA.
[Sloan, J.] NHGRI, NIH, Bethesda, MD 20892 USA.
[Dariotis, J.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Populat Family & Reprod Hlth, Baltimore, MD USA.
[Dariotis, J.] Univ Cincinnati, Coll Educ Criminal Justice & Human Serv, Cincinnati, OH USA.
[Biesecker, B. B.] NHGRI, Social & Behav Res Branch, NIH, Bethesda, MD 20892 USA.
RP Cohen, JS (reprint author), Kennedy Krieger Inst, Dept Neurol & Dev Med, 801 North Broadway,Room 564, Baltimore, MD 21205 USA.
EM cohenju@kennedykrieger.org
FU National Human Genome Research Institute
FX This research was supported by the Intramural Research Program of the
National Human Genome Research Institute. We thank the individuals with
NF1 who participated in the study and the NF1 support organizations,
Neurofibromatosis Inc and Children's Tumor Foundation, for assisting us
with study recruitment. This research was supported by the Intramural
Research Program of the National Human Genome Research Institute.
NR 26
TC 4
Z9 4
U1 0
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0009-9163
EI 1399-0004
J9 CLIN GENET
JI Clin. Genet.
PD NOV
PY 2015
VL 88
IS 5
BP 425
EP 430
DI 10.1111/cge.12551
PG 6
WC Genetics & Heredity
SC Genetics & Heredity
GA CT3BW
UT WOS:000362682200003
PM 25534182
ER
PT J
AU Vasu, S
Berg, M
Davidson-Moncada, J
Tian, X
Cullis, H
Childs, RW
AF Vasu, Sumithira
Berg, Maria
Davidson-Moncada, Jan
Tian, Xin
Cullis, Herb
Childs, Richard W.
TI A novel method to expand large numbers of CD56(+) natural killer cells
from a minute fraction of selectively accessed cryopreserved cord blood
for immunotherapy after transplantation
SO CYTOTHERAPY
LA English
DT Article
DE cryopreserved cord blood; expanded NK cells; ex vivo expansion; natural
killer cells; umbilical cord blood
ID HEMATOPOIETIC STEM-CELLS; ACUTE MYELOID-LEUKEMIA; ACTIVATING RECEPTORS;
BONE-MARROW; NK CELLS; T-CELLS; ALLOREACTIVITY; PROFILE; ADULTS; LIGAND
AB Background aims. Umbilical cord blood transplantation (UCBT) is increasingly used to treat acute leukemias. UCB units are thawed and infused in their entirety at transplant, precluding later use as immunotherapy to prevent or treat leukemia relapse. Methods. We developed a device that selectively thaws only 1 mL of the UCB unit, leaving the remaining UCB unit cryopreserved for subsequent transplantation. We also show that large numbers of CD56(+) natural killer (NK) cells can be expanded from these 1-mL fractions of selectively accessed UCB. Immunomagnetic depletion of CD3(+) cells of the 1-mL fraction was performed, and the cells were subsequently stimulated with irradiated Epstein-Barr virus transformed lymphoblastoid cell lines (EBV-LCLs) and set to culture in media containing interleukin (IL)-2. Results. When a 1:20 ratio of total nucleated cells to EBV-LCL feeder cells was used, day-21 and day-35 NK cell cultures initiated from 1 mL of UCB contained a median of 430 x 10(6) (range: 44-4321 x 10(6)) and 6092 x 10(6) (range: 165-20947 x 10(6)) CD3(-)CD56(+) NK cells. These cells expressed high levels of CD161, LFA-1, CD69, NKG2D, NKp30, NKp44, NKp80 and NKp46. UCB-derived NK cells were highly cytotoxic against K562 leukemia cells, although cytotoxicity was slightly lower than in expanded PBMC-derived NK cells. Conclusions. We have developed and optimized a strategy to selectively access a small fraction from cryopreserved UCB and show that large numbers of CD56(+) cells can be expanded from this selectively accessed fraction. This strategy presents a method to explore whether early adoptive transfer of NK cells expanded from the same UCB unit used for transplantation can prevent leukemic relapse and decrease graft-versus-host disease after UCBT.
C1 [Vasu, Sumithira] Ohio State Univ, Div Hematol, Columbus, OH 43210 USA.
[Berg, Maria; Childs, Richard W.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
[Davidson-Moncada, Jan] NCI, Med Oncol Branch, Bethesda, MD 20892 USA.
[Tian, Xin] NHLBI, Off Biostat Res, Bethesda, MD 20892 USA.
[Cullis, Herb] Amer Flouroseal Corp, Gaithersburg, MD USA.
RP Childs, RW (reprint author), NHLBI, NIH, Bldg 10,Room 3E-5330,10 Ctr Dr, Bethesda, MD 20892 USA.
EM childsr@nhlbi.nih.gov
OI Tian, Xin/0000-0003-1896-2462
FU Division of Intramural Research of the National Heart, Lung, and Blood
Institute, National Institutes of Health
FX This work was supported by the Division of Intramural Research of the
National Heart, Lung, and Blood Institute, National Institutes of
Health.
NR 49
TC 4
Z9 4
U1 0
U2 6
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1465-3249
EI 1477-2566
J9 CYTOTHERAPY
JI Cytotherapy
PD NOV
PY 2015
VL 17
IS 11
BP 1582
EP 1593
DI 10.1016/j.jcyt.2015.07.020
PG 12
WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell
Biology; Hematology; Medicine, Research & Experimental
SC Cell Biology; Biotechnology & Applied Microbiology; Hematology; Research
& Experimental Medicine
GA CT2DV
UT WOS:000362613100009
PM 26432560
ER
PT J
AU Hirschfeld, S
AF Hirschfeld, Steven
TI A child is a child is a child? Paediatric terminology in a health
context
SO DEVELOPMENTAL MEDICINE AND CHILD NEUROLOGY
LA English
DT Editorial Material
AB This commentary is on the systematic review by Clark et al. on pages 1011-1018 of this issue.
C1 Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD 20852 USA.
RP Hirschfeld, S (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD 20852 USA.
RI Hirschfeld, Steven/E-2987-2016
OI Hirschfeld, Steven/0000-0003-0627-7249
NR 1
TC 0
Z9 0
U1 0
U2 1
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 NOV
PY 2015
VL 57
IS 11
BP 985
EP 985
DI 10.1111/dmcn.12829
PG 1
WC Clinical Neurology; Pediatrics
SC Neurosciences & Neurology; Pediatrics
GA CT3YG
UT WOS:000362742200002
PM 26084814
ER
PT J
AU Morgun, A
Dzutsev, A
Dong, XX
Greer, RL
Sexton, DJ
Ravel, J
Schuster, M
Hsiao, W
Matzinger, P
Shulzhenko, N
AF Morgun, Andrey
Dzutsev, Amiran
Dong, Xiaoxi
Greer, Renee L.
Sexton, D. Joseph
Ravel, Jacques
Schuster, Martin
Hsiao, William
Matzinger, Polly
Shulzhenko, Natalia
TI Uncovering effects of antibiotics on the host and microbiota using
transkingdom gene networks
SO GUT
LA English
DT Article
ID PSEUDOMONAS-AERUGINOSA; INTESTINAL MICROBIOTA; COMMENSAL BACTERIA;
COEXPRESSION NETWORKS; IMMUNE-RESPONSES; GUT MICROBIOTA; PATHOGENESIS;
PROTEIN; CANCER; LIFE
AB Objective Despite widespread use of antibiotics for the treatment of life-threatening infections and for research on the role of commensal microbiota, our understanding of their effects on the host is still very limited.
Design Using a popular mouse model of microbiota depletion by a cocktail of antibiotics, we analysed the effects of antibiotics by combining intestinal transcriptome together with metagenomic analysis of the gut microbiota. In order to identify specific microbes and microbial genes that influence the host phenotype in antibiotic-treated mice, we developed and applied analysis of the transkingdom network.
Results We found that most antibiotic-induced alterations in the gut can be explained by three factors: depletion of the microbiota; direct effects of antibiotics on host tissues and the effects of remaining antibiotic-resistant microbes. Normal microbiota depletion mostly led to downregulation of different aspects of immunity. The two other factors (antibiotic direct effects on host tissues and antibiotic-resistant microbes) primarily inhibited mitochondrial gene expression and amounts of active mitochondria, increasing epithelial cell death. By reconstructing and analysing the transkingdom network, we discovered that these toxic effects were mediated by virulence/quorum sensing in antibiotic-resistant bacteria, a finding further validated using in vitro experiments.
Conclusions In addition to revealing mechanisms of antibiotic-induced alterations, this study also describes a new bioinformatics approach that predicts microbial components that regulate host functions and establishes a comprehensive resource on what, why and how antibiotics affect the gut in a widely used mouse model of microbiota depletion by antibiotics.
C1 [Morgun, Andrey; Dong, Xiaoxi] Oregon State Univ, Coll Pharm, Corvallis, OR 97331 USA.
[Dzutsev, Amiran] NCI, Canc & Inflammat Program, Leidos Biomed Res Inc, Frederick, MD 21701 USA.
[Greer, Renee L.; Shulzhenko, Natalia] Oregon State Univ, Coll Vet Med, Corvallis, OR 97331 USA.
[Sexton, D. Joseph; Schuster, Martin] Oregon State Univ, Dept Microbiol, Corvallis, OR 97331 USA.
[Ravel, Jacques] Univ Maryland, Sch Med, Inst Genome Sci, Baltimore, MD 21201 USA.
[Hsiao, William] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada.
[Morgun, Andrey; Matzinger, Polly; Shulzhenko, Natalia] NIAID, Ghost Lab, NIH, Bethesda, MD 20892 USA.
RP Shulzhenko, N (reprint author), Oregon State Univ, 105 Dryden, Corvallis, OR 97331 USA.
EM anemorgun@hotmail.com; natalia.shulzhenko@oregonstate.edu
OI Ravel, Jacques/0000-0002-0851-2233
FU Division of Intramural Research, National Institute of Allergy and
Infectious Diseases; Oregon State University Medical Research Foundation
of Oregon
FX Division of Intramural Research, National Institute of Allergy and
Infectious Diseases. Oregon State University Medical Research Foundation
of Oregon.
NR 64
TC 16
Z9 16
U1 2
U2 34
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0017-5749
EI 1468-3288
J9 GUT
JI Gut
PD NOV
PY 2015
VL 64
IS 11
BP 1732
EP 1743
DI 10.1136/gutjnl-2014-308820
PG 12
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA CT1WQ
UT WOS:000362593700010
PM 25614621
ER
PT J
AU Zoulim, F
Liang, TJ
Gerbes, AL
Aghemo, A
Deuffic-Burban, S
Dusheiko, G
Fried, MW
Pol, S
Rockstroh, JK
Terrault, NA
Wiktor, S
AF Zoulim, Fabien
Liang, T. Jake
Gerbes, Alexander L.
Aghemo, Alessio
Deuffic-Burban, Sylvie
Dusheiko, Geoffrey
Fried, Michael W.
Pol, Stanislas
Rockstroh, Juergen Kurt
Terrault, Norah A.
Wiktor, Stefan
TI Hepatitis C virus treatment in the real world: optimising treatment and
access to therapies
SO GUT
LA English
DT Article
ID SOFOSBUVIR PLUS RIBAVIRIN; GENOTYPE 1 INFECTION; SUSTAINED VIROLOGICAL
RESPONSE; TREATMENT-EXPERIENCED PATIENTS; DIRECT-ACTING ANTIVIRALS;
PROOF-OF-CONCEPT; PHASE 2A COHORT; OPEN-LABEL; LIVER-TRANSPLANTATION;
COST-EFFECTIVENESS
AB Chronic HCV infections represent a major worldwide public health problem and are responsible for a large proportion of liver related deaths, mostly because of HCV-associated hepatocellular carcinoma and cirrhosis. The treatment of HCV has undergone a rapid and spectacular revolution. In the past 5 years, the launch of direct acting antiviral drugs has seen sustained virological response rates reach 90% and above for many patient groups. The new treatments are effective, well tolerated, allow for shorter treatment regimens and offer new opportunities for previously excluded groups. This therapeutic revolution has changed the rules for treatment of HCV, moving the field towards an interferon-free era and raising the prospect of HCV eradication. This manuscript addresses the new challenges regarding treatment optimisation in the real world, improvement of antiviral efficacy in 'hard-to-treat' groups, the management of patients whose direct acting antiviral drug treatment was unsuccessful, and access to diagnosis and treatment in different parts of the world.
C1 [Zoulim, Fabien] Univ Lyon 1, Canc Res Ctr Lyon, Hosp Civils Lyon, INSERM,U1052, F-69003 Lyon, France.
[Liang, T. Jake] NIDDK, Liver Dis Branch, NIH, Bethesda, MD USA.
[Gerbes, Alexander L.] Univ Hosp Munich, Klinikum LMU Munchen Grosshadern, Liver Ctr Munich, Munich, Germany.
[Aghemo, Alessio] Fdn IRCCS Ca Granda Osped Maggiore Policlin, UO Gastroenterol & Epatol, Milan, Italy.
[Deuffic-Burban, Sylvie] INSERM, IAME, UMR 1137, Paris, France.
[Deuffic-Burban, Sylvie] Univ Paris Diderot, Sorbonne Paris Cite, Paris, France.
[Deuffic-Burban, Sylvie] INSERM, LIRIC UMR995, Lille, France.
[Deuffic-Burban, Sylvie] Univ Lille, Lille, France.
[Dusheiko, Geoffrey] Royal Free Hosp, UCL Inst Liver & Digest Hlth, London NW3 2QG, England.
[Fried, Michael W.] Univ N Carolina, UNC Liver Ctr, Chapel Hill, NC USA.
[Pol, Stanislas] Univ Paris 05, INSERM, Inst Pasteur, USM20, Paris, France.
[Pol, Stanislas] Univ Paris 05, Hop Cochin, AP HP, Dept Hepatol, Paris, France.
[Rockstroh, Juergen Kurt] Univ Hosp Bonn, Dept Med 1, Bonn, Germany.
[Terrault, Norah A.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Wiktor, Stefan] WHO, CH-1211 Geneva, Switzerland.
RP Zoulim, F (reprint author), Univ Lyon 1, Canc Res Ctr Lyon, Hosp Civils Lyon, INSERM,U1052, F-69003 Lyon, France.
EM fabien.zoulim@inserm.fr
FU Gilead Sciences; Janssen; Merck; AbbVie; BMS; MSD; Bristol-Myers Squibb;
Gilead; Glaxo; NIH; Roche; Boehringer Ingelheim; Vertex; Novartis;
Sanofi; Glaxo Smith Kline; Abbott laboratories; Cipla; ViiV; NEAT-ID;
Eisai; Biotest; Achillion; Gilead Sc
FX AA received consulting and lecture fees from Gilead Sciences, Janssen,
Merck, AbbVie, BMS, as well as grants and research support from Gilead
Sciences. SD-B reports receiving research grants from Janssen and MSD;
consultancy honoraria from AbbVie, Bristol-Myers Squibb, HEVA, Janssen,
MSD and Public Health Expertise; and lecture fees from Bristol-Myers
Squibb, Gilead and Janssen. GD acted as advisor to Gilead Sciences,
Merck, Bristol Myers Squibb, Janssen and AbbVie. MWF reports research
grant funding from AbbVie, Bristol-Myers Squibb, Gilead, Glaxo, Janssen,
Merck, NIH and consultant funding from AbbVie, Bristol-Myers Squibb,
Gilead, Glaxo, Janssen, Merck. ALG received grants from Gilead, MSD and
Roche and advisory board fees from Bristol-Myers Squibb. SP has received
consulting and lecturing fees from Bristol-Myers Squibb, Boehringer
Ingelheim, Janssen, Vertex, Gilead, Roche, MSD, Novartis, Abbvie, Sanofi
and Glaxo Smith Kline, and grants from Bristol-Myers Squibb, Gilead,
Roche and MSD. JKR has received consulting and lecturing fees from
Abbott laboratories, Abbvie, Bristol-Myers Squibb, Boehringer Ingelheim,
Cipla, Gilead, Janssen, MSD, ViiV, and grants from NEAT-ID and Gilead.
NAT received Grant support from Gilead, AbbVie, Eisai, Biotest, and
consulting/advisory board fees from Bristol-Myers Squibb, MSD,
Achillion, Janssen. FZ has received consulting and/or lecturing fees
from Abbvie, Bristol-Myers Squibb, Boehringer Ingelheim, Janssen, Gilead
Sc and MSD.
NR 88
TC 30
Z9 30
U1 3
U2 11
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0017-5749
EI 1468-3288
J9 GUT
JI Gut
PD NOV
PY 2015
VL 64
IS 11
BP 1824
EP 1833
DI 10.1136/gutjnl-2015-310421
PG 10
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA CT1WQ
UT WOS:000362593700022
PM 26449729
ER
PT J
AU Skinner, J
Huang, CY
Waisberg, M
Felgner, PL
Doumbo, OK
Ongoiba, A
Kayentao, K
Traore, B
Crompton, PD
Williamson, KC
AF Skinner, Jeff
Huang, Chiung-Yu
Waisberg, Michael
Felgner, Philip L.
Doumbo, Ogobara K.
Ongoiba, Aissata
Kayentao, Kassoum
Traore, Boubacar
Crompton, Peter D.
Williamson, Kim C.
TI Plasmodium falciparum Gametocyte-Specific Antibody Profiling Reveals
Boosting through Natural Infection and Identifies Potential Markers of
Gametocyte Exposure
SO INFECTION AND IMMUNITY
LA English
DT Article
ID TRANSMISSION-BLOCKING ANTIBODIES; SEXUAL STAGE ANTIGENS;
IMMUNE-RESPONSES; VACCINE CANDIDATE; SEASONAL TRANSMISSION; MALARIA
INFECTIONS; LIFE-CYCLE; PROTEIN; PFS230; EXPRESSION
AB Malaria elimination efforts would benefit from vaccines that block transmission of Plasmodium falciparum gametocytes from humans to mosquitoes. A clear understanding of gametocyte-specific antibody responses in exposed populations could help determine whether transmission-blocking vaccines (TBV) would be boosted by natural gametocyte exposure, and also inform the development of serologic tools to monitor gametocyte exposure in populations targeted for malaria elimination. To this end, plasma was collected from Malian children and adults before and after the 6-month malaria season and probed against a microarray containing 1,204 P. falciparum proteins. Using publicly available proteomic data, we classified 91 proteins as gametocyte specific and 69 as proteins not expressed by gametocytes. The overall breadth and magnitude of gametocyte-specific IgG responses increased during the malaria season, although they were consistently lower than IgG responses to nongametocyte antigens. Notably, IgG specific for the TBV candidates Pfs48/45 and Pfs230 increased during the malaria season. In addition, IgGs specific for the gametocyte proteins Pfmdv1, Pfs16, PF3D7_1346400, and PF3D7_1024800 were detected in nearly all subjects, suggesting that seroconversion to these proteins may be a sensitive indicator of gametocyte exposure, although further studies are needed to determine the specificity and kinetics of these potential serologic markers. These findings suggest that TBV-induced immunity would be boosted through natural gametocyte exposure, and that antibody responses to particular antigens may reliably indicate gametocyte exposure.
C1 [Skinner, Jeff; Waisberg, Michael; Crompton, Peter D.] NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA.
[Huang, Chiung-Yu] Johns Hopkins Univ, Div Biostat & Bioinformat, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA.
[Felgner, Philip L.; Ongoiba, Aissata; Kayentao, Kassoum] Univ Calif Irvine, Dept Med, Div Infect Dis, Irvine, CA 92717 USA.
[Felgner, Philip L.] Antigen Discovery Inc, Irvine, CA USA.
[Doumbo, Ogobara K.; Traore, Boubacar] Univ Sci Tech & Technol Bamako, Mali Int Ctr Excellence Res, Bamako, Mali.
[Williamson, Kim C.] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA.
[Williamson, Kim C.] Loyola Univ, Dept Biol, Chicago, IL 60626 USA.
RP Crompton, PD (reprint author), NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA.
EM pcrompton@niaid.nih.gov; kwilli4@luc.edu
RI Crompton, Peter/N-1130-2016;
OI Skinner, Jeff/0000-0001-5697-0442
FU Division of Intramural Research at the National Institute of Allergy and
Infectious Diseases, National Institutes of Health; Public Health
Service grants from the National Institute of Allergy and Infectious
Diseases, National Institutes of Health [AI069314, R43AI066791,
U54AI065359, R01AI095916]
FX This study was supported by the Division of Intramural Research at the
National Institute of Allergy and Infectious Diseases, National
Institutes of Health, and by Public Health Service grants AI069314
(K.C.W.), R43AI066791 (P.L.F.), U54AI065359 (P.L.F.), and R01AI095916
(P.L.F.) from the National Institute of Allergy and Infectious Diseases,
National Institutes of Health.
NR 50
TC 2
Z9 2
U1 3
U2 13
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0019-9567
EI 1098-5522
J9 INFECT IMMUN
JI Infect. Immun.
PD NOV
PY 2015
VL 83
IS 11
BP 4229
EP 4236
DI 10.1128/IAI.00644-15
PG 8
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA CT0NU
UT WOS:000362494000006
PM 26283330
ER
PT J
AU Greenberg, DE
Sturdevant, DE
Marshall-Batty, KR
Chu, J
Pettinato, AM
Virtaneva, K
Lane, J
Geller, BL
Porcella, SF
Gallin, JI
Holland, SM
Zarember, KA
AF Greenberg, David E.
Sturdevant, Daniel E.
Marshall-Batty, Kimberly R.
Chu, Jessica
Pettinato, Anthony M.
Virtaneva, Kimmo
Lane, John
Geller, Bruce L.
Porcella, Stephen F.
Gallin, John I.
Holland, Steven M.
Zarember, Kol A.
TI Simultaneous Host-Pathogen Transcriptome Analysis during Granulibacter
bethesdensis Infection of Neutrophils from Healthy Subjects and Patients
with Chronic Granulomatous Disease
SO INFECTION AND IMMUNITY
LA English
DT Article
ID GROUP-A STREPTOCOCCUS; GENE-EXPRESSION; POLYMORPHONUCLEAR LEUKOCYTES;
CONSTITUTIVE APOPTOSIS; FRANCISELLA-TULARENSIS; ASPERGILLUS-FUMIGATUS;
CYNOMOLGUS MACAQUES; BACTERIAL PATHOGENS; PERITONEAL-DIALYSIS;
SEQUENCE-ANALYSIS
AB Polymorphonuclear leukocytes (PMN) from patients with chronic granulomatous disease (CGD) fail to produce microbicidal concentrations of reactive oxygen species (ROS) due to mutations in NOX2. Patients with CGD suffer from severe, life-threatening infections and inflammatory complications. Granulibacter bethesdensis is an emerging Gram-negative pathogen in CGD that resists killing by PMN of CGD patients (CGD PMN) and inhibits PMN apoptosis through unknown mechanisms. Microarray analysis was used to study mRNA expression in PMN from healthy subjects (normal PMN) and CGD PMN during incubation with G. bethesdensis and, simultaneously, in G. bethesdensis with normal and CGD PMN. We detected upregulation of antiapoptotic genes (e.g., XIAP and GADD45B) and downregulation of proapoptotic genes (e.g., CASP8 and APAF1) in infected PMN. Transcript and protein levels of inflammation-and immunity-related genes were also altered. Upon interaction with PMN, G. bethesdensis altered the expression of ROS resistance genes in the presence of normal but not CGD PMN. Levels of bacterial stress response genes, including the ClpB gene, increased during phagocytosis by both normal and CGD PMN demonstrating responses to oxygen-independent PMN antimicrobial systems. Antisense knockdown demonstrated that ClpB is dispensable for extracellular growth but is essential for bacterial resistance to both normal and CGD PMN. Metabolic adaptation of Granulibacter growth in PMN included the upregulation of pyruvate dehydrogenase. Pharmacological inhibition of pyruvate dehydrogenase by triphenylbismuthdichloride was lethal to Granulibacter. This study expands knowledge of microbial pathogenesis of Granulibacter in cells from permissive (CGD) and nonpermissive (normal) hosts and identifies potentially druggable microbial factors, such as pyruvate dehydrogenase and ClpB, to help combat this antibiotic-resistant pathogen.
C1 [Greenberg, David E.; Marshall-Batty, Kimberly R.; Holland, Steven M.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
[Greenberg, David E.; Marshall-Batty, Kimberly R.] Univ Texas SW Med Ctr Dallas, Dept Med, Dallas, TX 75390 USA.
[Greenberg, David E.; Marshall-Batty, Kimberly R.] Univ Texas SW Med Ctr Dallas, Dept Microbiol, Dallas, TX 75390 USA.
[Sturdevant, Daniel E.; Virtaneva, Kimmo; Lane, John; Porcella, Stephen F.] NIAID, Genom Unit, Res Technol Branch, Rocky Mt Labs,NIH, Hamilton, MT USA.
[Chu, Jessica; Pettinato, Anthony M.; Gallin, John I.; Zarember, Kol A.] NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA.
[Geller, Bruce L.] Oregon State Univ, Dept Microbiol, Corvallis, OR 97331 USA.
RP Zarember, KA (reprint author), NIAID, Host Def Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM kzarember@niaid.nih.gov
OI Chu, Jessica/0000-0002-5763-873X
FU Intramural Research Program of the NIH, NIAID
FX This work was supported in part by the Intramural Research Program of
the NIH, NIAID.
NR 55
TC 1
Z9 1
U1 1
U2 5
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0019-9567
EI 1098-5522
J9 INFECT IMMUN
JI Infect. Immun.
PD NOV
PY 2015
VL 83
IS 11
BP 4277
EP 4292
DI 10.1128/IAI.00778-15
PG 16
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA CT0NU
UT WOS:000362494000011
PM 26283340
ER
PT J
AU Cash, DR
Noinaj, N
Buchanan, SK
Cornelissen, CN
AF Cash, Devin R.
Noinaj, Nicholas
Buchanan, Susan K.
Cornelissen, Cynthia Nau
TI Beyond the Crystal Structure: Insight into the Function and Vaccine
Potential of TbpA Expressed by Neisseria gonorrhoeae
SO INFECTION AND IMMUNITY
LA English
DT Article
ID BINDING PROTEIN-A; GONOCOCCAL TRANSFERRIN RECEPTOR; COMPLEMENT FACTOR-H;
ENHANCED IMMUNOGENICITY; PATHOGENIC NEISSERIA; LIGAND-BINDING; IRON
COMPOUNDS; GENITAL-TRACT; IDENTIFICATION; CEFTRIAXONE
AB Neisseria gonorrhoeae, the causative agent of the sexually transmitted infection gonorrhea, is not preventable by vaccination and is rapidly developing resistance to antibiotics. However, the transferrin (Tf) receptor system, composed of TbpA and TbpB, is an ideal target for novel therapeutics and vaccine development. Using a three-dimensional structure of gonococcal TbpA, we investigated two hypotheses, i.e., that loop-derived antibodies can interrupt ligand-receptor interactions in the native bacterium and that the loop 3 helix is a critical functional domain. Preliminary loop-derived antibodies, as well as optimized second-generation antibodies, demonstrated similar modest ligand-blocking effects on the gonococcal surface but different effects in Escherichia coli. Mutagenesis of loop 3 helix residues was employed, generating 11 mutants. We separately analyzed the mutants' abilities to (i) bind Tf and (ii) internalize Tf-bound iron in the absence of the coreceptor TbpB. Single residue mutations resulted in up to 60% reductions in ligand binding and up to 85% reductions in iron utilization. All strains were capable of growing on Tf as the sole iron source. Interestingly, in the presence of TbpB, only a 30% reduction in Tf-iron utilization was observed, indicating that the coreceptor can compensate for TbpA impairment. Complete deletion of the loop 3 helix of TbpA eliminated the abilities to bind Tf, internalize iron, and grow with Tf as the sole iron source. Our studies demonstrate that while the loop 3 helix is a key functional domain, its function does not exclusively rely on any single residue.
C1 [Cash, Devin R.; Cornelissen, Cynthia Nau] Virginia Commonwealth Univ, Dept Microbiol & Immunol, Richmond, VA 23298 USA.
[Noinaj, Nicholas; Buchanan, Susan K.] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Cornelissen, CN (reprint author), Virginia Commonwealth Univ, Dept Microbiol & Immunol, Richmond, VA 23298 USA.
EM cncornel@vcu.edu
FU Public Health Service grants from the National Institute of Allergy and
Infectious Diseases, National Institutes of Health [R01 AI065555, R01
AI084400, U19 AI31496]; National Institute of Allergy and Infectious
Diseases, National Institutes of Health [F30 AI112199]; intramural
research program of the NIH National Institute of Diabetes and Digestive
and Kidney Diseases
FX Funding for this work was provided to C.N.C. by Public Health Service
grants R01 AI065555, R01 AI084400, and U19 AI31496 from the National
Institute of Allergy and Infectious Diseases, National Institutes of
Health. D.R.C. was supported by fellowship grant F30 AI112199 from the
National Institute of Allergy and Infectious Diseases, National
Institutes of Health. N.N. and S.K.B. were supported by the intramural
research program of the NIH National Institute of Diabetes and Digestive
and Kidney Diseases.
NR 49
TC 1
Z9 1
U1 1
U2 4
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0019-9567
EI 1098-5522
J9 INFECT IMMUN
JI Infect. Immun.
PD NOV
PY 2015
VL 83
IS 11
BP 4438
EP 4449
DI 10.1128/IAI.00762-15
PG 12
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA CT0NU
UT WOS:000362494000025
PM 26351283
ER
PT J
AU DuPont, RL
Compton, WM
McLellan, AT
AF DuPont, Robert L.
Compton, Wilson M.
McLellan, A. Thomas
TI Five-Year Recovery: A New Standard for Assessing Effectiveness of
Substance Use Disorder Treatment
SO JOURNAL OF SUBSTANCE ABUSE TREATMENT
LA English
DT Editorial Material
ID HEALTH-PROGRAMS; OUTCOMES; PREDICTORS; DEPENDENCE
C1 [DuPont, Robert L.] Inst Behav & Hlth Inc, Rockville, MD 20852 USA.
[Compton, Wilson M.] NIDA, Rockville, MD 20852 USA.
[McLellan, A. Thomas] Treatment Res Inst, Philadelphia, PA 19106 USA.
RP Compton, WM (reprint author), NIDA, 6001 Execut Blvd, Rockville, MD 20852 USA.
EM bobdupont@aol.com; wcompton@nida.nih.gov; TMcLellan@tresearch.org
NR 21
TC 4
Z9 4
U1 0
U2 2
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0740-5472
J9 J SUBST ABUSE TREAT
JI J. Subst. Abus. Treat.
PD NOV
PY 2015
VL 58
BP 1
EP 5
DI 10.1016/j.jsat.2015.06.024
PG 5
WC Psychology, Clinical; Substance Abuse
SC Psychology; Substance Abuse
GA CS8BZ
UT WOS:000362312000001
PM 26277423
ER
PT J
AU Shih, JH
Albert, PS
Mendola, P
Grantz, KL
AF Shih, Joanna H.
Albert, Paul S.
Mendola, Pauline
Grantz, Katherine L.
TI Modelling the type and timing of consecutive events: application to
predicting preterm birth in repeated pregnancies
SO JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES C-APPLIED STATISTICS
LA English
DT Article
DE Adverse pregnancy outcome; Normal copula; Polychotomous random-effects
logistic model; Pre-eclampsia; Preterm birth; Repeated pregnancies
ID COMPETING RISK; OUTCOMES
AB Predicting the occurrence and timing of adverse pregnancy events such as preterm birth is an important analytical challenge in obstetrical practice. Developing statistical approaches that can be used to assess the risk and timing of these adverse events will provide clinicians with tools for individualized risk assessment that account for a woman's prior pregnancy history. Often adverse pregnancy outcomes are subject to competing events; for example, interest may focus on the occurrence of pre-eclampsia-related preterm birth, where preterm birth for other reasons may serve as a competing event. We propose modelling the type and timing of adverse outcomes in repeated pregnancies. We formulate a joint model, where types of adverse outcomes across repeated pregnancies are modelled by using a polychotomous logistic regression model with random effects, and gestational ages at delivery are modelled conditionally on the types of adverse outcome. The correlation between gestational ages conditional on the adverse pregnancies is modelled by the semiparametric normal copula function. We present a two-stage estimation method and develop the asymptotic theory for the estimators proposed. The model and estimation procedure proposed are applied to the National Institute of Child Health and Human Development consecutive pregnancies study data and evaluated by simulations.
C1 [Shih, Joanna H.] NCI, Bethesda, MD 20892 USA.
[Albert, Paul S.; Mendola, Pauline; Grantz, Katherine L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Rockville, MD USA.
RP Shih, JH (reprint author), NCI, Biometr Res Branch, Room 5W124,9609 Med Ctr Dr, Bethesda, MD 20892 USA.
EM jshih@mail.nih.gov
OI Mendola, Pauline/0000-0001-5330-2844; Grantz,
Katherine/0000-0003-0276-8534
FU NICHD NIH HHS [HHSN275200800002I]
NR 13
TC 0
Z9 0
U1 0
U2 5
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0035-9254
EI 1467-9876
J9 J R STAT SOC C-APPL
JI J. R. Stat. Soc. Ser. C-Appl. Stat.
PD NOV
PY 2015
VL 64
IS 5
BP 711
EP 730
DI 10.1111/rssc.12100
PG 20
WC Statistics & Probability
SC Mathematics
GA CT3FL
UT WOS:000362692500001
PM 27239073
ER
PT J
AU Tietbohl, CK
Rendle, KAS
Halley, MC
May, SG
Lin, GA
Frosch, DL
AF Tietbohl, Caroline K.
Rendle, Katharine A. S.
Halley, Meghan C.
May, Suepattra G.
Lin, Grace A.
Frosch, Dominick L.
TI Implementation of Patient Decision Support Interventions in Primary
Care: The Role of Relational Coordination
SO MEDICAL DECISION MAKING
LA English
DT Article
DE relational coordination; decision support interventions; patient
engagement; implementation; qualitative methodologies
ID CLINICAL-PRACTICE; AIDS
AB Background. The benefits of patient decision support interventions (DESIs) have been well documented. However, DESIs remain difficult to incorporate into clinical practice. Relational coordination (RC) has been shown to improve performance and quality of care in health care settings. This study aims to demonstrate how applying RC theory to DESI implementation could elucidate underlying issues limiting widespread uptake. Methods. Five primary care clinics in Northern California participated in a DESI implementation project. We used a deductive thematic approach guided by behaviors outlined in RC theory to analyze qualitative data collected from ethnographic field notes documenting the implementation process and focus groups with health care professionals. We then systematically compared the qualitative findings with quantitative DESI distribution data. Results. Based on DESI distribution rates, clinics were placed into 3 performance categories: high, middle, and low. Qualitative data illustrated how each clinic's performance related to RC behaviors. Consistent with RC theory, the high-performing clinic exhibited frequent, timely, and accurate communication and positive working relationships. The 3 middle-performing clinics exhibited high-quality communication within physician-staff teams but limited communication regarding DESI implementation across the clinic. The lowest-performing clinic was characterized by contentious relationships and inadequate communication. Limitations. Limitations of the study include nonrandom selection of clinics and limited geographic diversity. In addition, ethnographic data collected documented only DESI implementation practices and not larger staff interactions contributing to RC. Conclusions. These findings suggest that a high level of RC within clinical settings may be a key component and facilitator of successful DESI implementation. Future attempts to integrate DESIs into clinical practice should consider incorporating interventions designed to increase positive RC behaviors as a potential means to improve uptake.
C1 [Tietbohl, Caroline K.; Frosch, Dominick L.] Univ Calif Los Angeles, Los Angeles, CA 90095 USA.
[Tietbohl, Caroline K.; Rendle, Katharine A. S.; Halley, Meghan C.; May, Suepattra G.; Frosch, Dominick L.] Palo Alto Med Fdn, Res Inst, Palo Alto, CA 94301 USA.
[Rendle, Katharine A. S.] NCI, Canc Prevent Fellowship Program, Canc Prevent Div, Bethesda, MD 20892 USA.
[May, Suepattra G.] Precis Hlth Econ, Los Angeles, CA USA.
[Lin, Grace A.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Frosch, Dominick L.] Gordon & Betty Moore Fdn, Palo Alto, CA USA.
RP Tietbohl, CK (reprint author), Univ Calif Los Angeles, 405 Hilgard Ave, Los Angeles, CA 90095 USA.
EM ctietbohl@ucla.edu
FU Informed Medical Decisions Foundation
FX This study was funded by a grant from the Informed Medical Decisions
Foundation. The funders did not influence data collection,
interpretation, or publication. The authors also thank Harold S. Luft,
PhD, Laurel Trujillo, MD, and R. Adams Dudley, MD, MBA, for their
assistance in designing the project and Carla Arellano-Bravo for her
contributions to data collection.
NR 22
TC 1
Z9 1
U1 2
U2 5
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0272-989X
EI 1552-681X
J9 MED DECIS MAKING
JI Med. Decis. Mak.
PD NOV
PY 2015
VL 35
IS 8
BP 987
EP 998
DI 10.1177/0272989X15602886
PG 12
WC Health Care Sciences & Services; Medical Informatics
SC Health Care Sciences & Services; Medical Informatics
GA CS9YT
UT WOS:000362450800007
PM 26314727
ER
PT J
AU Holmberg, C
Waters, EA
Whitehouse, K
Daly, M
McCaskill-Stevens, W
AF Holmberg, Christine
Waters, Erika A.
Whitehouse, Katie
Daly, Mary
McCaskill-Stevens, Worta
TI My Lived Experiences Are More Important Than Your Probabilities: The
Role of Individualized Risk Estimates for Decision Making about
Participation in the Study of Tamoxifen and Raloxifene (STAR)
SO MEDICAL DECISION MAKING
LA English
DT Article
DE individualized risk information; lived experiences; narrative
interviews; decision making; chemoprevention; breast cancer risk
ID BREAST-CANCER CHEMOPREVENTION; SURGICAL ADJUVANT BREAST; BOWEL PROJECT;
PRIMARY-CARE; P-2 TRIAL; US WOMEN; PREVENTION; HEALTH; INFORMATION;
PERCEPTIONS
AB Background: Decision-making experts emphasize that understanding and using probabilistic information are important for making informed decisions about medical treatments involving complex risk-benefit tradeoffs. Yet empirical research demonstrates that individuals may not use probabilities when making decisions. Objectives: To explore decision making and the use of probabilities for decision making from the perspective of women who were risk-eligible to enroll in the Study of Tamoxifen and Raloxifene (STAR). Methods: We conducted narrative interviews with 20 women who agreed to participate in STAR and 20 women who declined. The project was based on a narrative approach. Analysis included the development of summaries of each narrative, and thematic analysis with developing a coding scheme inductively to code all transcripts to identify emerging themes. Results: Interviewees explained and embedded their STAR decisions within experiences encountered throughout their lives. Such lived experiences included but were not limited to breast cancer family history, a personal history of breast biopsies, and experiences or assumptions about taking tamoxifen or medicines more generally. Conclusions: Women's explanations of their decisions about participating in a breast cancer chemoprevention trial were more complex than decision strategies that rely solely on a quantitative risk-benefit analysis of probabilities derived from populations In addition to precise risk information, clinicians and risk communicators should recognize the importance and legitimacy of lived experience in individual decision making.
C1 [Holmberg, Christine; Whitehouse, Katie] Charite, Berlin Sch Publ Hlth, D-13347 Berlin, Germany.
[Waters, Erika A.] Washington Univ, Sch Med, Dept Surg, St Louis, MO 63110 USA.
[Daly, Mary] Fox Chase Canc Ctr, Philadelphia, PA 19111 USA.
[McCaskill-Stevens, Worta] NCI, Rockville, MD USA.
RP Holmberg, C (reprint author), Charite, Berlin Sch Publ Hlth, Seestr 73 Haus 10, D-13347 Berlin, Germany.
EM Christine.holmberg@charite.de
FU Public Health Service from the National Cancer Institute, Department of
Health and Human Services [UG1-189867]; Barnes-Jewish Hospital
Foundation
FX Supported by Public Health Service Grant UG1-189867 from the National
Cancer Institute, Department of Health and Human Services. This research
was conducted while Holmberg and Waters were cancer prevention fellows
at the National Cancer Institute. Waters was also supported by the
Barnes-Jewish Hospital Foundation. Revision accepted for publication 7
June 2015.
NR 50
TC 2
Z9 2
U1 4
U2 12
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0272-989X
EI 1552-681X
J9 MED DECIS MAKING
JI Med. Decis. Mak.
PD NOV
PY 2015
VL 35
IS 8
BP 1010
EP 1022
DI 10.1177/0272989X15594382
PG 13
WC Health Care Sciences & Services; Medical Informatics
SC Health Care Sciences & Services; Medical Informatics
GA CS9YT
UT WOS:000362450800009
PM 26183166
ER
PT J
AU Radin, RG
Rothman, KJ
Hatch, EE
Mikkelsen, EM
Sorensen, HT
Riis, AH
Fox, MP
Wise, LA
AF Radin, Rose G.
Rothman, Kenneth J.
Hatch, Elizabeth E.
Mikkelsen, Ellen M.
Sorensen, Henrik T.
Riis, Anders H.
Fox, Matthew P.
Wise, Lauren A.
TI Maternal Recall Error in Retrospectively Reported Time-to-Pregnancy: an
Assessment and Bias Analysis
SO PAEDIATRIC AND PERINATAL EPIDEMIOLOGY
LA English
DT Article
DE Bias (Epidemiology); Cohort Studies; Fertility Determinants
ID COHORT PROFILE; FECUNDABILITY; QUESTIONNAIRE; VALIDITY; FERTILITY
AB BackgroundEpidemiologic studies of fecundability often use retrospectively measured time-to-pregnancy (TTP), thereby introducing potential for recall error. Little is known about how recall error affects the bias and precision of the fecundability odds ratio (FOR) in such studies.
MethodsUsing data from the Danish Snart-Gravid Study (2007-12), we quantified error for TTP recalled in the first trimester of pregnancy relative to prospectively measured TTP among 421 women who enrolled at the start of their pregnancy attempt and became pregnant within 12 months. We defined recall error as retrospectively measured TTP minus prospectively measured TTP. Using linear regression, we assessed mean differences in recall error by maternal characteristics. We evaluated the resulting bias in the FOR and 95% confidence interval (CI) using simulation analyses that compared corrected and uncorrected retrospectively measured TTP values.
ResultsRecall error (mean=-0.11 months, 95% CI -0.25, 0.04) was not appreciably associated with maternal age, gravidity, or recent oral contraceptive use. Women with TTP>2 months were more likely to underestimate their TTP than women with TTP2 months (unadjusted mean difference in error: -0.40 months, 95% CI -0.71, -0.09). FORs of recent oral contraceptive use calculated from prospectively measured, retrospectively measured, and corrected TTPs were 0.82 (95% CI 0.67, 0.99), 0.74 (95% CI 0.61, 0.90), and 0.77 (95% CI 0.62, 0.96), respectively.
ConclusionsRecall error was small on average among pregnancy planners who became pregnant within 12 months. Recall error biased the FOR of recent oral contraceptive use away from the null by 10%. Quantitative bias analysis of the FOR can help researchers quantify the bias from recall error.
C1 [Radin, Rose G.; Rothman, Kenneth J.; Hatch, Elizabeth E.; Sorensen, Henrik T.; Fox, Matthew P.; Wise, Lauren A.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02118 USA.
[Fox, Matthew P.] Boston Univ, Ctr Global Hlth & Dev, Boston, MA 02118 USA.
[Wise, Lauren A.] Boston Univ, Slone Epidemiol Ctr, Boston, MA 02118 USA.
[Radin, Rose G.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Intramural Populat Hlth Res, North Bethesda, MD USA.
[Rothman, Kenneth J.] RTI Hlth Solut, Res Triangle Pk, NC USA.
[Mikkelsen, Ellen M.; Sorensen, Henrik T.; Riis, Anders H.] Aarhus Univ Hosp, Dept Clin Epidemiol, DK-8000 Aarhus, Denmark.
RP Radin, RG (reprint author), Boston Univ, Sch Publ Hlth, Dept Epidemiol, 715 Albany St, Boston, MA 02118 USA.
EM radin@bu.edu
OI Riis, Anders Hammerich/0000-0002-6684-4068
FU National Institutes of Health [R21-HD050264]; Danish Medical Research
Council [271-07-0338]; National Institutes of Health Intramural Research
Training Award; [T32-HD052458]
FX This study was supported by the National Institutes of Health
(R21-HD050264) and the Danish Medical Research Council (271-07-0338).
RGR was supported by training grant T32-HD052458 and by a National
Institutes of Health Intramural Research Training Award. The content of
this article is solely the responsibility of the authors and does not
represent the official views of the National Institutes of Health.
NR 20
TC 5
Z9 5
U1 1
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0269-5022
EI 1365-3016
J9 PAEDIATR PERINAT EP
JI Paediatr. Perinat. Epidemiol.
PD NOV
PY 2015
VL 29
IS 6
BP 576
EP 588
DI 10.1111/ppe.12245
PG 13
WC Public, Environmental & Occupational Health; Obstetrics & Gynecology;
Pediatrics
SC Public, Environmental & Occupational Health; Obstetrics & Gynecology;
Pediatrics
GA CT3RG
UT WOS:000362723900014
PM 26443987
ER
PT J
AU Compton, WM
Boyle, M
Wargo, E
AF Compton, Wilson M.
Boyle, Maureen
Wargo, Eric
TI Prescription opioid abuse: Problems and responses
SO PREVENTIVE MEDICINE
LA English
DT Editorial Material
DE Prescription opioid abuse; Addiction; Overdose
ID DRUG OVERDOSE DEATHS; UNITED-STATES; NALOXONE DISTRIBUTION; POLICE
OFFICERS; PAIN RELIEVERS; PREVENTION; EPIDEMIC; PROGRAMS; LEVEL;
MASSACHUSETTS
AB Prescription opioid abuse and addiction, along with consequences such as overdose death and increasing transition to heroin use, constitute a devastating public health problem in the United States. Increasingly it is clear that overprescription of these medications over the past two decades has been a major upstream driver of the opioid abuse epidemic. This commentary considers the factors that have led to overprescription of opioids by clinicians, discusses recent evidence casting doubt on the efficacy of opioids for treating chronic pain, and describes the ongoing efforts by federal and community stakeholders to address this epidemic-for example, supporting prescription drug monitoring programs and improved clinician training in pain management to help reduce the supply of opioids, increasing dissemination of evidence-based primary prevention programs to reduce demand for opioids, and expanding access to effective opioid agonist therapies and antagonist medications for both treatment and overdose prevention. Published by Elsevier Inc.
C1 [Compton, Wilson M.; Boyle, Maureen; Wargo, Eric] NIDA, NIH, US Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
RP Compton, WM (reprint author), NIDA, 6001 Executive Blvd,MSC 9581, Bethesda, MD 20892 USA.
EM wcompton@nida.nih.gov
NR 58
TC 14
Z9 14
U1 10
U2 42
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 NOV
PY 2015
VL 80
SI SI
BP 5
EP 9
DI 10.1016/j.ypmed.2015.04.003
PG 5
WC Public, Environmental & Occupational Health; Medicine, General &
Internal
SC Public, Environmental & Occupational Health; General & Internal Medicine
GA CT0DF
UT WOS:000362463400002
PM 25871819
ER
PT J
AU DuMond, JF
He, Y
Burg, MB
Ferraris, JD
AF DuMond, Jenna F.
He, Yi
Burg, Maurice B.
Ferraris, Joan D.
TI Expression, fermentation and purification of a predicted intrinsically
disordered region of the transcription factor, NFAT5
SO PROTEIN EXPRESSION AND PURIFICATION
LA English
DT Article
DE Intrinsically disordered proteins; Transcription factors; Hypertonicity;
Fermentation
ID ENHANCER-BINDING PROTEIN; TONICITY
AB Hypertonicity stimulates Nuclear Factor of Activated T-cells 5 (NFAT5) nuclear localization and transactivating activity. Many transcription factors are known to contain intrinsically disordered regions (IDRs) which become more structured with local environmental changes such as osmolality, temperature and tonicity. The transactivating domain of NFAT5 is predicted to be intrinsically disordered under normal tonicity, and under high NaCl, the activity of this domain is increased. To study the binding of coregulatory proteins at IDRs a cDNA construct expressing the NFAT5 TAD was created and transformed into Escherichia colt cells. Transformed E. coli cells were mass produced by fermentation and extracted by cell lysis to release the NFAT5 TAD. The NFAT5 TAD was subsequently purified using a His-tag column, cation exchange chromatography as well as hydrophobic interaction chromatography and then characterized by mass spectrometry (MS). Published by Elsevier Inc.
C1 [DuMond, Jenna F.; Burg, Maurice B.; Ferraris, Joan D.] NHLBI, NIH, Syst Biol Ctr, Bethesda, MD 20892 USA.
[He, Yi] NHLBI, NIH, Biochem & Biophys Ctr, Bethesda, MD 20892 USA.
RP DuMond, JF (reprint author), NHLBI, NIH, Syst Biol Ctr, Bethesda, MD 20892 USA.
EM jenna.dumond@nih.gov; hey4@nhlbi.nih.gov; burgm@mail.nih.gov;
ferraris@nhlbi.nih.gov
FU NIH NHLBI Biochemistry Core
FX We would like to thank the by the NIH NHLBI Biochemistry Core for their
support of this work acquiring the HPLC-MS data and analysis.
NR 14
TC 0
Z9 0
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 1046-5928
EI 1096-0279
J9 PROTEIN EXPRES PURIF
JI Protein Expr. Purif.
PD NOV
PY 2015
VL 115
BP 141
EP 145
DI 10.1016/j.pep.2015.08.003
PG 5
WC Biochemical Research Methods; Biochemistry & Molecular Biology;
Biotechnology & Applied Microbiology
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology
GA CT2HS
UT WOS:000362623200019
PM 26256058
ER
PT J
AU Barker, TV
Reeb-Sutherland, B
Degnan, KA
Walker, OL
Chronis-Tuscano, A
Henderson, HA
Pine, DS
Fox, NA
AF Barker, Tyson V.
Reeb-Sutherland, Bethany
Degnan, Kathryn A.
Walker, Olga L.
Chronis-Tuscano, Andrea
Henderson, Heather A.
Pine, Daniel S.
Fox, Nathan A.
TI Contextual startle responses moderate the relation between behavioral
inhibition and anxiety in middle childhood
SO PSYCHOPHYSIOLOGY
LA English
DT Article
DE Temperament; Risk factors; Startle; Behavioral inhibition; Anxiety
ID ADOLESCENT SOCIAL ANXIETY; TEMPERAMENT; DISORDERS; CHILDREN;
REPLICATION; MODULATION; REACTIVITY; RISK; FEAR; STABILITY
AB Behavioral inhibition (BI), a temperament characterized in early childhood by wariness and avoidance of novelty, is a risk factor for anxiety disorders. An enhanced startle response has been observed in adolescents characterized with BI in childhood, particularly when they also manifest concurrent symptoms of anxiety. However, no prior study has examined relations among BI, startle responsivity, and anxiety in a prospective manner. Data for the present study were from a longitudinal study of infant temperament. Maternal reports and observations of BI were assessed at ages 2 and 3. At age 7, participants completed a startle procedure, while electromyography was collected, where participants viewed different colors on a screen that were associated with either the delivery of an aversive stimulus (i.e., puff of air to the larynx; threat cue) or the absence of the aversive stimulus (i.e., safety cue). Parental reports of child anxiety were collected when children were 7 and 9 years of age. Results revealed that startle responses at age 7 moderated the relation between early BI and 9-year anxiety. These findings provide insight into one potential mechanism that may place behaviorally inhibited children at risk for anxiety.
C1 [Barker, Tyson V.; Degnan, Kathryn A.; Walker, Olga L.; Fox, Nathan A.] Univ Maryland, Dept Human Dev & Quantitat Methodol, College Pk, MD 20742 USA.
[Reeb-Sutherland, Bethany] Florida Int Univ, Dept Psychol, Miami, FL 33199 USA.
[Chronis-Tuscano, Andrea] Univ Maryland, Dept Psychol, College Pk, MD 20742 USA.
[Henderson, Heather A.] Univ Waterloo, Dept Psychol, Waterloo, ON N2L 3G1, Canada.
[Pine, Daniel S.] NIMH, Sect Dev & Affect Neurosci, Bethesda, MD 20892 USA.
RP Barker, TV (reprint author), Univ Maryland, Dept Human Dev & Quantitat Methodol, 3304 Benjamin Bldg, College Pk, MD 20742 USA.
EM tvbarker@umd.edu
FU Intramural NIH HHS; NICHD NIH HHS [5T32HD007542, T32 HD007542]; NIMH NIH
HHS [MH093349, R01 MH074454]
NR 43
TC 4
Z9 4
U1 2
U2 14
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0048-5772
EI 1469-8986
J9 PSYCHOPHYSIOLOGY
JI Psychophysiology
PD NOV
PY 2015
VL 52
IS 11
BP 1544
EP 1549
DI 10.1111/psyp.12517
PG 6
WC Psychology, Biological; Neurosciences; Physiology; Psychology;
Psychology, Experimental
SC Psychology; Neurosciences & Neurology; Physiology
GA CT0OW
UT WOS:000362497000013
PM 26332665
ER
PT J
AU Tarasenko, TN
Singh, LN
Chatterji-Len, M
Zerfas, PM
Cusmano-Ozog, K
McGuire, PJ
AF Tarasenko, Tatyana N.
Singh, Larry N.
Chatterji-Len, Milani
Zerfas, Patricia M.
Cusmano-Ozog, Kristina
McGuire, Peter J.
TI Kupffer cells modulate hepatic fatty acid oxidation during infection
with PR8 influenza
SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
LA English
DT Article
DE beta-oxidation; Fatty acids; Metabolism; Innate immune response;
Influenza
ID UREA CYCLE DISORDERS; ACUTE METABOLIC DECOMPENSATION;
TUMOR-NECROSIS-FACTOR; ISOLATED RAT HEPATOCYTES; NUTRITIONAL MANAGEMENT;
ADAPTIVE IMMUNITY; ENERGY-METABOLISM; NITRIC-OXIDE; FACTOR-ALPHA; LIVER
AB In response to infection, patients with inborn errors of metabolism may develop a functional deterioration termed metabolic decompensation. The biochemical hallmarks of this disruption of metabolic homeostasis are disease specific and may include acidosis, hyperammonemia or hypoglycemia. In a model system previously published by our group, we noted that during influenza infection, mice displayed a depression in hepatic mitochondrial enzymes involved in nitrogen metabolism. Based on these findings, we hypothesized that this normal adaptation may extend to other metabolic pathways, and as such, may impact various inborn errors of metabolism. Since the liver is a critical organ in inborn errors of metabolism, we carried out untargeted metabolomic profiling of livers using mass spectrometry in C57B1/6 mice infected with influenza to characterize metabolic adaptation. Pathway analysis of metabolomic data revealed reductions in CoA synthesis, and long chain fatty acyl CoA and camitine species. These metabolic adaptations coincided with a depression in hepatic long chain 3-oxidation mRNA and protein. To our surprise, the metabolic changes observed occurred in conjunction with a hepatic innate immune response, as demonstrated by transcriptional profiling and flow cytometry. By employing an immunomodulation strategy to deplete Kupffer cells, we were able to improve the expression of multiple genes involved in 3-oxidation. Based on these findings, we are the first to suggest that the role of the liver as an immunologic organ is central in the pathophysiology of hepatic metabolic decompensation in inborn errors of metabolism due to respiratory viral infection. (C) 2015 Published by Elsevier B.V.
C1 [Tarasenko, Tatyana N.; Chatterji-Len, Milani; McGuire, Peter J.] NHGRI, Metab Infect & Immun Unit, NIH, Bethesda, MD 20892 USA.
[Singh, Larry N.] Childrens Hosp Philadelphia, Dept Pathol, Ctr Mitochondrial & Epigen Med, Philadelphia, PA 19104 USA.
[Zerfas, Patricia M.] NIH, Off Res Serv, Div Vet Resources, Bethesda, MD 20892 USA.
[Cusmano-Ozog, Kristina] Childrens Natl Med Ctr, Biochem Genet & Metab Lab, Washington, DC 20010 USA.
RP McGuire, PJ (reprint author), NHGRI, NIH, 49 Convent Dr,Room 4A62, Bethesda, MD 20892 USA.
EM peter.mcguire@nih.gov
FU Intramural Research Program of the National Institutes of Health
[HG200381-03]
FX This work was supported by the Intramural Research Program of the
National Institutes of Health (HG200381-03).
NR 57
TC 0
Z9 0
U1 0
U2 7
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0925-4439
EI 0006-3002
J9 BBA-MOL BASIS DIS
JI Biochim. Biophys. Acta-Mol. Basis Dis.
PD NOV
PY 2015
VL 1852
IS 11
BP 2391
EP 2401
DI 10.1016/j.bbadis.2015.08.021
PG 11
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA CS5QJ
UT WOS:000362132700006
PM 26319418
ER
PT J
AU Blair, RJ
AF Blair, R. James
TI Reward Processing, Functional Connectivity, Psychopathy, and Research
Domain Criteria
SO BIOLOGICAL PSYCHIATRY
LA English
DT Editorial Material
ID DISRUPTIVE BEHAVIOR DISORDERS; EXPECTED VALUE
C1 NIMH, Sect Affect & Cognit Neurosci, NIH, Bethesda, MD 20892 USA.
RP Blair, RJ (reprint author), NIMH, Sect Affect & Cognit Neurosci, NIH, Bldg 15k,Room 300-E,MSC 2670,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM jamesblair@mail.nih.gov
FU Intramural NIH HHS [Z01 MH002860-03]
NR 10
TC 0
Z9 0
U1 4
U2 18
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0006-3223
EI 1873-2402
J9 BIOL PSYCHIAT
JI Biol. Psychiatry
PD NOV 1
PY 2015
VL 78
IS 9
BP 592
EP 593
DI 10.1016/j.biopsych.2015.08.014
PG 2
WC Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA CS7OB
UT WOS:000362271800001
PM 26434627
ER
PT J
AU Barrett, T
Turkbey, B
Choyke, PL
AF Barrett, T.
Turkbey, B.
Choyke, P. L.
TI PI-RADS version 2: what you need to know
SO CLINICAL RADIOLOGY
LA English
DT Review
ID CONTRAST-ENHANCED MRI; BENIGN PROSTATIC HYPERPLASIA; DIFFUSION-WEIGHTED
MRI; RADICAL PROSTATECTOMY; CANCER-DETECTION; EXTRACAPSULAR EXTENSION;
ACTIVE SURVEILLANCE; PERIPHERAL ZONE; INITIAL BIOPSY; FOCAL THERAPY
AB Prostate cancer is the second most prevalent cancer in men worldwide and its incidence is expected to double by 2030. Multi-parametric magnetic resonance imaging (MRI) incorporating anatomical and functional imaging has now been validated as a means of detecting and characterising prostate tumours and can aid in risk stratification and treatment selection. The European Society of Urogenital Radiology (ESUR) in 2012 established the Prostate Imaging-Reporting and Data System (PI-RADS) guidelines aimed at standardising the acquisition, interpretation and reporting of prostate MRI. Subsequent experience and technical developments have highlighted some limitations, and a joint steering committee formed by the American College of Radiology, ESUR, and the AdMeTech Foundation have recently announced an updated version of the proposals. We summarise the main proposals of PI-RADS version 2, explore the evidence behind the recommendations, and highlight key differences for the benefit of those already familiar with the original. (C) 2015 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
C1 [Barrett, T.] Addenbrookes Hosp, Dept Radiol, Cambridge CB2 0QQ, England.
[Barrett, T.] Univ Cambridge, Cambridge CB2 0QQ, England.
[Turkbey, B.; Choyke, P. L.] NCI, Mol Imaging Program, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Barrett, T (reprint author), Addenbrookes Hosp, Dept Radiol, Cambridge CB2 0QQ, England.
EM tristan.barrett@addenbrookes.nhs.uk
FU Cancer Research UK; Engineering and Physical Sciences Research Council
Imaging Centre in Cambridge; Engineering and Physical Sciences Research
Council Imaging Centre in Manchester; NIHR Biomedical Research Centre
FX Author TB is supported by the Cancer Research UK and Engineering and
Physical Sciences Research Council Imaging Centre in Cambridge and
Manchester and the NIHR Biomedical Research Centre.
NR 48
TC 25
Z9 26
U1 0
U2 4
PU W B SAUNDERS CO LTD
PI LONDON
PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND
SN 0009-9260
EI 1365-229X
J9 CLIN RADIOL
JI Clin. Radiol.
PD NOV
PY 2015
VL 70
IS 11
BP 1165
EP 1176
DI 10.1016/j.crad.2015.06.093
PG 12
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA CS2MF
UT WOS:000361904300003
PM 26231470
ER
PT J
AU Pandiyan, P
Zhu, JF
AF Pandiyan, Pushpa
Zhu, Jinfang
TI Origin and functions of pro-inflammatory cytokine producing Foxp3(+)
regulatory T cells
SO CYTOKINE
LA English
DT Review
DE T-reg; Th17; IL-17; Foxp3; Suppression; Inflammation; Cytokine;
Reprogramming
ID VERSUS-HOST-DISEASE; TRANSCRIPTION FACTOR FOXP3; TOLL-LIKE-RECEPTORS;
TREG-MEDIATED SUPPRESSION; ROR-GAMMA-T; TH17 CELLS; IN-VIVO;
CANDIDA-ALBICANS; CUTTING EDGE; TGF-BETA
AB CD4(+)CD25(+)Foxp3(+) regulatory cells (T-regs) are a special lineage of cells central in the maintenance of immune homeostasis, and are targeted for human immunotherapy. They are conventionally associated with the production of classical anti-inflammatory cytokines such as IL-10, TGF-beta and IL-35, consistent to their anti-inflammatory functions. However, emerging evidence show that they also express effector cytokines such as IFN-gamma and IL-17A under inflammatory conditions. While some studies reveal that these pro-inflammatory cytokine producing Foxp3(+) regulatory cells retain their suppressive ability, others believe that these cells are dys-regulated and are associated with perpetuation of immunopathology. Therefore the development of these cells may challenge the efficacy of human T-reg therapy. Mechanistically, toll-like receptor (TLR) ligands and the pro-inflammatory cytokine milieu have been shown to play important roles in the induction of effector cytokines in T-regs. Here we review the mechanisms of development and the possible functions of pro-inflammatory cytokine producing Foxp3+ T-regs. (C) 2015 Elsevier Ltd. All rights reserved.
C1 [Pandiyan, Pushpa] Case Western Reserve Univ, Sch Dent Med, Dept Biol Sci, Cleveland, OH 44106 USA.
[Zhu, Jinfang] NIAID, Mol & Cellular Immunoregulat Unit, Immunol Lab, NIH, Bethesda, MD 20892 USA.
RP Pandiyan, P (reprint author), Case Western Reserve Univ, Sch Dent Med, Dept Biol Sci, Cleveland, OH 44106 USA.
EM pxp226@case.edu
RI Zhu, Jinfang/B-7574-2012
FU Intramural NIH HHS [ZIA AI001169-03]; NIAMS NIH HHS [P30 AR039750,
P30AR39750]
NR 202
TC 11
Z9 15
U1 3
U2 24
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1043-4666
EI 1096-0023
J9 CYTOKINE
JI Cytokine
PD NOV
PY 2015
VL 76
IS 1
BP 13
EP 24
DI 10.1016/j.cyto.2015.07.005
PG 12
WC Biochemistry & Molecular Biology; Cell Biology; Immunology
SC Biochemistry & Molecular Biology; Cell Biology; Immunology
GA CS1XO
UT WOS:000361862400002
PM 26165923
ER
PT J
AU Abdi, K
Singh, NJ
AF Abdi, Kaveh
Singh, Nevil J.
TI Making many from few: IL-12p40 as a model for the combinatorial assembly
of heterodimeric cytokines
SO CYTOKINE
LA English
DT Review
DE IL-12; Dendritic cells; Innate activation; T cell differentiation;
Hypothesis; Immunological class; Tissue immunity
ID NITRIC-OXIDE SYNTHASE; P40 HOMODIMER; T-CELLS; ADAPTIVE IMMUNITY;
IFN-GAMMA; MYCOBACTERIAL INFECTION; INTERLEUKIN-12 P40;
HUMAN-LYMPHOCYTES; DENDRITIC CELLS; MICE
AB How dendritic cells (DCs) gather information from the local milieu at a site of infection or injury and communicate this to influence adaptive immunity is not well understood. We and others have reported that soon after microbial encounter, DCs secrete the p40 subunit of IL-12, by itself, in a monomeric form. Based on recent data that this p40 monomer subsequently associates with p35 released from other cells to generate functional IL-12, we proposed that p40 can function as a DC-derived probe which samples the composition of the local milieu by looking for other binding partners. In this opinion, we discuss how such a sampling function might generate an elaborate combinatorial "code" of heterodimeric cytokines, capable of conveying location-specific information to cells downstream of DC activation, including NK and T cells. (C) 2015 Elsevier Ltd. All rights reserved.
C1 [Abdi, Kaveh] NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA.
[Singh, Nevil J.] Univ Maryland, Sch Med, Dept Microbiol & Immunol, Baltimore, MD 21201 USA.
RP Singh, NJ (reprint author), Univ Maryland, Sch Med, Dept Microbiol & Immunol, 685 W Baltimore St,HSF1,Room 380, Baltimore, MD 21201 USA.
EM nsingh@som.umaryland.edu
FU NIAID NIH HHS [R01 AI110719, R01AI110719, R56 AI113313, R56AI113313]
NR 66
TC 3
Z9 3
U1 2
U2 7
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1043-4666
EI 1096-0023
J9 CYTOKINE
JI Cytokine
PD NOV
PY 2015
VL 76
IS 1
BP 53
EP 57
DI 10.1016/j.cyto.2015.07.026
PG 5
WC Biochemistry & Molecular Biology; Cell Biology; Immunology
SC Biochemistry & Molecular Biology; Cell Biology; Immunology
GA CS1XO
UT WOS:000361862400006
PM 26242928
ER
PT J
AU Goldbach-Mansky, R
AF Goldbach-Mansky, Raphaela
TI Genetically defined autoinflammatory diseases
SO CYTOKINE
LA English
DT Meeting Abstract
CT 3rd Annual Meeting of the International-Cytokine-and-Interferon-Society
(ICIS)
CY OCT 11-14, 2015
CL Bamberg, GERMANY
SP Int Cytokine & Interferon Soc
C1 [Goldbach-Mansky, Raphaela] NIAMS, Translat Autoinflammatory Dis Sect, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1043-4666
EI 1096-0023
J9 CYTOKINE
JI Cytokine
PD NOV
PY 2015
VL 76
IS 1
MA 6
BP 58
EP 58
DI 10.1016/j.cyto.2015.08.010
PG 1
WC Biochemistry & Molecular Biology; Cell Biology; Immunology
SC Biochemistry & Molecular Biology; Cell Biology; Immunology
GA CS1XO
UT WOS:000361862400009
ER
PT J
AU Sher, A
Antonelli, L
Feng, C
Costa, D
Andrade, B
O'Garra, A
Mayer-Marber, K
AF Sher, Alan
Antonelli, L.
Feng, C.
Costa, D.
Andrade, B.
O'Garra, A.
Mayer-Marber, K.
TI The probacterial activity of Type I interferons: a target for disease
intervention?
SO CYTOKINE
LA English
DT Meeting Abstract
CT 3rd Annual Meeting of the International-Cytokine-and-Interferon-Society
(ICIS)
CY OCT 11-14, 2015
CL Bamberg, GERMANY
SP Int Cytokine & Interferon Soc
C1 [Sher, Alan; Costa, D.; Mayer-Marber, K.] NIAID, NIH, Bethesda, MD 20892 USA.
[Antonelli, L.] Fiocruz MS, Belo Horizonte, MG, Brazil.
[Feng, C.] Univ Sydney, Sydney, NSW 2006, Australia.
[Andrade, B.] Fiocruz MS, Salvador, BA, Brazil.
[O'Garra, A.] Francis Crick Inst, London, England.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1043-4666
EI 1096-0023
J9 CYTOKINE
JI Cytokine
PD NOV
PY 2015
VL 76
IS 1
MA 15
BP 59
EP 60
DI 10.1016/j.cyto.2015.08.019
PG 2
WC Biochemistry & Molecular Biology; Cell Biology; Immunology
SC Biochemistry & Molecular Biology; Cell Biology; Immunology
GA CS1XO
UT WOS:000361862400018
ER
PT J
AU Mayer-Barber, K
AF Mayer-Barber, Katrin
TI Type I IFN modulation as host-directed therapy during non-viral
pulmonary infections
SO CYTOKINE
LA English
DT Meeting Abstract
CT 3rd Annual Meeting of the International-Cytokine-and-Interferon-Society
(ICIS)
CY OCT 11-14, 2015
CL Bamberg, GERMANY
SP Int Cytokine & Interferon Soc
C1 [Mayer-Barber, Katrin] NIAID, NIH, Lab Clin Infect Dis, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1043-4666
EI 1096-0023
J9 CYTOKINE
JI Cytokine
PD NOV
PY 2015
VL 76
IS 1
MA 149
BP 64
EP 64
DI 10.1016/j.cyto.2015.08.040
PG 1
WC Biochemistry & Molecular Biology; Cell Biology; Immunology
SC Biochemistry & Molecular Biology; Cell Biology; Immunology
GA CS1XO
UT WOS:000361862400038
ER
PT J
AU Yoo, KH
Shin, HY
Oh, SM
Hennighausen, L
AF Yoo, Kyung Hyun
Shin, Ha Youn
Oh, Sumin
Hennighausen, Lothar
TI Fences make good neighbors: staying out of your neighbor's genetic yard
SO CYTOKINE
LA English
DT Meeting Abstract
CT 3rd Annual Meeting of the International-Cytokine-and-Interferon-Society
(ICIS)
CY OCT 11-14, 2015
CL Bamberg, GERMANY
SP Int Cytokine & Interferon Soc
C1 [Yoo, Kyung Hyun; Shin, Ha Youn; Oh, Sumin; Hennighausen, Lothar] NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1043-4666
EI 1096-0023
J9 CYTOKINE
JI Cytokine
PD NOV
PY 2015
VL 76
IS 1
MA 251
BP 65
EP 65
DI 10.1016/j.cyto.2015.08.043
PG 1
WC Biochemistry & Molecular Biology; Cell Biology; Immunology
SC Biochemistry & Molecular Biology; Cell Biology; Immunology
GA CS1XO
UT WOS:000361862400041
ER
PT J
AU Bedsaul, J
Zaritsky, L
Zoon, K
AF Bedsaul, Jacquelyn
Zaritsky, Luna
Zoon, Kathryn
TI The diverse roles of type I interferon in response to EMCV and SeV
infections
SO CYTOKINE
LA English
DT Meeting Abstract
CT 3rd Annual Meeting of the International-Cytokine-and-Interferon-Society
(ICIS)
CY OCT 11-14, 2015
CL Bamberg, GERMANY
SP Int Cytokine & Interferon Soc
C1 [Bedsaul, Jacquelyn; Zaritsky, Luna; Zoon, Kathryn] NIAID, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1043-4666
EI 1096-0023
J9 CYTOKINE
JI Cytokine
PD NOV
PY 2015
VL 76
IS 1
MA 31
BP 69
EP 69
DI 10.1016/j.cyto.2015.08.061
PG 1
WC Biochemistry & Molecular Biology; Cell Biology; Immunology
SC Biochemistry & Molecular Biology; Cell Biology; Immunology
GA CS1XO
UT WOS:000361862400058
ER
PT J
AU Zaritsky, L
Bedsaul, J
Zoon, K
AF Zaritsky, Luna
Bedsaul, Jacquelyn
Zoon, Kathryn
TI Virus MOI affects type I IFN subtype induction profiles and ISGs
SO CYTOKINE
LA English
DT Meeting Abstract
CT 3rd Annual Meeting of the International-Cytokine-and-Interferon-Society
(ICIS)
CY OCT 11-14, 2015
CL Bamberg, GERMANY
SP Int Cytokine & Interferon Soc
C1 [Zaritsky, Luna; Bedsaul, Jacquelyn; Zoon, Kathryn] NIAID, NIH, Bethesda, MD USA.
NR 0
TC 1
Z9 1
U1 0
U2 2
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1043-4666
EI 1096-0023
J9 CYTOKINE
JI Cytokine
PD NOV
PY 2015
VL 76
IS 1
MA 30
BP 69
EP 69
DI 10.1016/j.cyto.2015.08.060
PG 1
WC Biochemistry & Molecular Biology; Cell Biology; Immunology
SC Biochemistry & Molecular Biology; Cell Biology; Immunology
GA CS1XO
UT WOS:000361862400057
ER
PT J
AU Gibbert, K
Lavender, K
Peterson, ME
Munch, J
Piehler, J
Santiago, ML
Verheyen, J
Hasenkrug, K
Dittmer, U
AF Gibbert, Kathrin
Lavender, Kerry.
Peterson, Mann E.
Muench, Jan
Piehler, Jacob
Santiago, Mario L.
Verheyen, Jens
Hasenkrug, Kim
Dittmer, Ulf
TI Treatment with interferon alpha subtype 14 potently suppresses HIV
infection in humanized mice
SO CYTOKINE
LA English
DT Meeting Abstract
CT 3rd Annual Meeting of the International-Cytokine-and-Interferon-Society
(ICIS)
CY OCT 11-14, 2015
CL Bamberg, GERMANY
SP Int Cytokine & Interferon Soc
C1 [Gibbert, Kathrin; Verheyen, Jens; Dittmer, Ulf] Univ Duisburg Essen, Essen, Germany.
[Lavender, Kerry.; Peterson, Mann E.; Hasenkrug, Kim] NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, NIH, Hamilton, MT USA.
[Muench, Jan] Univ Ulm, Med Ctr, Inst Mol Virol, D-89069 Ulm, Germany.
[Piehler, Jacob] Univ Osnabruck, D-49069 Osnabruck, Germany.
[Santiago, Mario L.] Univ Colorado, Denver, CO 80202 USA.
NR 0
TC 0
Z9 0
U1 0
U2 3
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1043-4666
EI 1096-0023
J9 CYTOKINE
JI Cytokine
PD NOV
PY 2015
VL 76
IS 1
MA 41
BP 71
EP 72
DI 10.1016/j.cyto.2015.08.071
PG 2
WC Biochemistry & Molecular Biology; Cell Biology; Immunology
SC Biochemistry & Molecular Biology; Cell Biology; Immunology
GA CS1XO
UT WOS:000361862400068
ER
PT J
AU Donnelly, RP
Sheikh, F
Dickensheets, H
Ramalingam, T
Helming, L
Gordon, S
AF Donnelly, Raymond P.
Sheikh, Faruk
Dickensheets, Harold
Ramalingam, Thirumalai
Helming, Laura
Gordon, Siamon
TI The IL-13 receptor-alpha 1 chain is essential for induction of the
alternative macrophage activation pathway by IL-13 but not IL-4
SO CYTOKINE
LA English
DT Meeting Abstract
CT 3rd Annual Meeting of the International-Cytokine-and-Interferon-Society
(ICIS)
CY OCT 11-14, 2015
CL Bamberg, GERMANY
SP Int Cytokine & Interferon Soc
C1 [Donnelly, Raymond P.; Sheikh, Faruk; Dickensheets, Harold] US FDA, Rockville, MD 20857 USA.
[Ramalingam, Thirumalai] NIAID, Bethesda, MD USA.
[Helming, Laura] Tech Univ Munich, Inst Med Microbiol Immunol & Hyg, D-80290 Munich, Germany.
[Gordon, Siamon] Univ Oxford, Oxford OX1 2JD, England.
NR 0
TC 0
Z9 0
U1 1
U2 2
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1043-4666
EI 1096-0023
J9 CYTOKINE
JI Cytokine
PD NOV
PY 2015
VL 76
IS 1
MA 43
BP 72
EP 72
DI 10.1016/j.cyto.2015.08.073
PG 1
WC Biochemistry & Molecular Biology; Cell Biology; Immunology
SC Biochemistry & Molecular Biology; Cell Biology; Immunology
GA CS1XO
UT WOS:000361862400070
ER
PT J
AU Schmeisser, H
Balinsky, C
Singh, K
Sreedhara, K
Dolan, M
Garboczi, D
Zoon, K
AF Schmeisser, Hana
Balinsky, Corey
Singh, Kavita
Sreedhara, Karthik
Dolan, Michael
Garboczi, David
Zoon, Kathryn
TI Characterization of the antiviral properties of IFIT3
SO CYTOKINE
LA English
DT Meeting Abstract
CT 3rd Annual Meeting of the International-Cytokine-and-Interferon-Society
(ICIS)
CY OCT 11-14, 2015
CL Bamberg, GERMANY
SP Int Cytokine & Interferon Soc
C1 [Schmeisser, Hana; Balinsky, Corey; Sreedhara, Karthik; Zoon, Kathryn] NIAID, NIH, Cytokine Biol Sect, Bethesda, MD 20892 USA.
[Singh, Kavita; Garboczi, David] NIAID, NIH, Struct Biol Unit, Rockville, MD 20852 USA.
[Dolan, Michael] NIAID, NIH, Bioinformat & Computat Biosci Branch, Bethesda, MD 20814 USA.
NR 0
TC 0
Z9 0
U1 1
U2 3
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1043-4666
EI 1096-0023
J9 CYTOKINE
JI Cytokine
PD NOV
PY 2015
VL 76
IS 1
MA 45
BP 72
EP 72
DI 10.1016/j.cyto.2015.08.075
PG 1
WC Biochemistry & Molecular Biology; Cell Biology; Immunology
SC Biochemistry & Molecular Biology; Cell Biology; Immunology
GA CS1XO
UT WOS:000361862400072
ER
PT J
AU Young, H
Valencia, J
Bae, H
Haines, D
Lockett, S
Karwan, M
Hanson, C
Barlow, A
AF Young, Howard
Valencia, Julio
Bae, Heekyong
Haines, Diana
Lockett, Stephen
Karwan, Megan
Hanson, Charlotte
Barlow, Alec
TI Moderate chronic levels of IFN-g induced an effective anti-melanoma
response with limited autoimmune effects
SO CYTOKINE
LA English
DT Meeting Abstract
CT 3rd Annual Meeting of the International-Cytokine-and-Interferon-Society
(ICIS)
CY OCT 11-14, 2015
CL Bamberg, GERMANY
SP Int Cytokine & Interferon Soc
C1 [Young, Howard; Valencia, Julio; Bae, Heekyong; Haines, Diana; Lockett, Stephen; Karwan, Megan; Hanson, Charlotte; Barlow, Alec] NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1043-4666
EI 1096-0023
J9 CYTOKINE
JI Cytokine
PD NOV
PY 2015
VL 76
IS 1
MA 56
BP 75
EP 75
DI 10.1016/j.cyto.2015.08.086
PG 1
WC Biochemistry & Molecular Biology; Cell Biology; Immunology
SC Biochemistry & Molecular Biology; Cell Biology; Immunology
GA CS1XO
UT WOS:000361862400083
ER
PT J
AU Bae, H
Valencia, JC
Hodge, DL
Sanford, ME
Hanson, CA
Back, T
Karwan, M
Feng, DC
Gao, B
Park, O
Tsuneyama, K
Leung, PS
Gershwin, ME
Young, HA
AF Bae, Heekyong
Valencia, Julio C.
Hodge, Deborah L.
Sanford, Michael E.
Hanson, Charlotte A.
Back, Tim
Karwan, Megan
Feng, Dechun
Gao, Bin
Park, Ogyi
Tsuneyama, Koichi
Leung, Patrick S.
Gershwin, M. Eric
Young, Howard A.
TI Deletion of the IFN-gamma 3 ' UTR AU-rich element results in autoimmune
cholangitis in female C57/BL6 mice
SO CYTOKINE
LA English
DT Meeting Abstract
CT 3rd Annual Meeting of the International-Cytokine-and-Interferon-Society
(ICIS)
CY OCT 11-14, 2015
CL Bamberg, GERMANY
SP Int Cytokine & Interferon Soc
C1 [Bae, Heekyong; Valencia, Julio C.; Hodge, Deborah L.; Sanford, Michael E.; Hanson, Charlotte A.; Back, Tim; Young, Howard A.] NCI, Expt Immunol Lab, Canc & Inflammat Program, Ctr Canc Res, Frederick, MD 21701 USA.
[Karwan, Megan] NCI, Lab Anim Sci, Frederick, MD 21701 USA.
[Feng, Dechun; Gao, Bin] NIAAA, Lab Liver Dis, Rockville, MD 20852 USA.
[Park, Ogyi] Johns Hopkins Univ, Sch Med, Russell H Morgan Dept Radiol & Radiol Sci, Baltimore, MD 21218 USA.
[Tsuneyama, Koichi] Univ Tokushima, Dept Mol & Environm Pathol, Grad Sch, Tokushima, Japan.
[Leung, Patrick S.; Gershwin, M. Eric] Univ Calif Davis, Div Rheumatol Allergy & Clin Immunol, Davis, CA 95616 USA.
NR 0
TC 0
Z9 0
U1 0
U2 5
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1043-4666
EI 1096-0023
J9 CYTOKINE
JI Cytokine
PD NOV
PY 2015
VL 76
IS 1
MA 62
BP 76
EP 76
DI 10.1016/j.cyto.2015.08.092
PG 1
WC Biochemistry & Molecular Biology; Cell Biology; Immunology
SC Biochemistry & Molecular Biology; Cell Biology; Immunology
GA CS1XO
UT WOS:000361862400089
ER
PT J
AU Durum, SK
Hixon, J
Senkevitch, E
Cramer, S
Barata, J
Walsh, S
Li, WQ
AF Durum, Scott Kenneth
Hixon, Julie
Senkevitch, Emilee
Cramer, Sarah
Barata, Joao
Walsh, Scott
Li, Wenqing
TI Targeting the IL-7R pathway in leukemia
SO CYTOKINE
LA English
DT Meeting Abstract
CT 3rd Annual Meeting of the International-Cytokine-and-Interferon-Society
(ICIS)
CY OCT 11-14, 2015
CL Bamberg, GERMANY
SP Int Cytokine & Interferon Soc
C1 [Durum, Scott Kenneth; Hixon, Julie; Senkevitch, Emilee; Cramer, Sarah; Li, Wenqing] NCI, NIH, Frederick, MD 21701 USA.
[Barata, Joao] Univ Lisbon, P-1699 Lisbon, Portugal.
[Walsh, Scott] Univ Maryland, College Pk, MD USA.
NR 0
TC 0
Z9 0
U1 1
U2 4
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1043-4666
EI 1096-0023
J9 CYTOKINE
JI Cytokine
PD NOV
PY 2015
VL 76
IS 1
MA 64
BP 76
EP 76
DI 10.1016/j.cyto.2015.08.094
PG 1
WC Biochemistry & Molecular Biology; Cell Biology; Immunology
SC Biochemistry & Molecular Biology; Cell Biology; Immunology
GA CS1XO
UT WOS:000361862400091
ER
PT J
AU Fish, EN
McCarthy, SDS
Hoenen, T
Branch, DR
AF Fish, Eleanor N.
McCarthy, Stephen D. S.
Hoenen, Thomas
Branch, Donald R.
TI IFN-beta treatment for Ebola virus disease: Bench to bedside
SO CYTOKINE
LA English
DT Meeting Abstract
CT 3rd Annual Meeting of the International-Cytokine-and-Interferon-Society
(ICIS)
CY OCT 11-14, 2015
CL Bamberg, GERMANY
SP Int Cytokine & Interferon Soc
C1 [Fish, Eleanor N.] Univ Hlth Network, Toronto, ON, Canada.
[Fish, Eleanor N.; McCarthy, Stephen D. S.; Branch, Donald R.] Univ Toronto, Toronto, ON M5S 1A1, Canada.
[Hoenen, Thomas] NIAID, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 2
U2 9
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1043-4666
EI 1096-0023
J9 CYTOKINE
JI Cytokine
PD NOV
PY 2015
VL 76
IS 1
MA 68
BP 77
EP 77
DI 10.1016/j.cyto.2015.08.098
PG 1
WC Biochemistry & Molecular Biology; Cell Biology; Immunology
SC Biochemistry & Molecular Biology; Cell Biology; Immunology
GA CS1XO
UT WOS:000361862400095
ER
PT J
AU Green, DS
Johnson, CL
Zoon, KC
AF Green, Daniel S.
Johnson, Chase L.
Zoon, Kathryn C.
TI A monocyte and interferon based cell therapy for the treatment of
ovarian cancer
SO CYTOKINE
LA English
DT Meeting Abstract
CT 3rd Annual Meeting of the International-Cytokine-and-Interferon-Society
(ICIS)
CY OCT 11-14, 2015
CL Bamberg, GERMANY
SP Int Cytokine & Interferon Soc
C1 [Green, Daniel S.; Johnson, Chase L.; Zoon, Kathryn C.] NIAID, Cytokine Biol Sect, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 3
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1043-4666
EI 1096-0023
J9 CYTOKINE
JI Cytokine
PD NOV
PY 2015
VL 76
IS 1
MA 69
BP 78
EP 78
DI 10.1016/j.cyto.2015.08.099
PG 1
WC Biochemistry & Molecular Biology; Cell Biology; Immunology
SC Biochemistry & Molecular Biology; Cell Biology; Immunology
GA CS1XO
UT WOS:000361862400096
ER
PT J
AU O'Brien, T
Pfeiffer, R
Paquin, A
Kuhs, KL
Chen, S
Howell, C
Prokunina-Olsson, L
AF O'Brien, Thomas
Pfeiffer, Ruth
Paquin, Ashley
Kuhs, Krystle Lang
Chen, Sabrina
Howell, Charles
Prokunina-Olsson, Ludmila
TI Comparison of IFNL4-Delta G/TT and IFNL3 rs4803217 for association with
hepatitis C virus clearance
SO CYTOKINE
LA English
DT Meeting Abstract
CT 3rd Annual Meeting of the International-Cytokine-and-Interferon-Society
(ICIS)
CY OCT 11-14, 2015
CL Bamberg, GERMANY
SP Int Cytokine & Interferon Soc
C1 [O'Brien, Thomas; Pfeiffer, Ruth; Paquin, Ashley; Kuhs, Krystle Lang; Prokunina-Olsson, Ludmila] NCI, Bethesda, MD 20892 USA.
[Chen, Sabrina] Informat Management Serv Inc, Calverton, MD USA.
[Howell, Charles] Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1043-4666
EI 1096-0023
J9 CYTOKINE
JI Cytokine
PD NOV
PY 2015
VL 76
IS 1
MA 89
BP 81
EP 81
DI 10.1016/j.cyto.2015.08.116
PG 1
WC Biochemistry & Molecular Biology; Cell Biology; Immunology
SC Biochemistry & Molecular Biology; Cell Biology; Immunology
GA CS1XO
UT WOS:000361862400113
ER
PT J
AU Onabajo, O
Prokunina-Olsson, L
AF Onabajo, Olusegun
Prokunina-Olsson, Ludmila
TI Anti-proliferative and cell death-inducing effects of interferon
lambda-4 (IFNL4) may contribute differentially to HCV pathogenesis and
cancer
SO CYTOKINE
LA English
DT Meeting Abstract
CT 3rd Annual Meeting of the International-Cytokine-and-Interferon-Society
(ICIS)
CY OCT 11-14, 2015
CL Bamberg, GERMANY
SP Int Cytokine & Interferon Soc
C1 [Onabajo, Olusegun; Prokunina-Olsson, Ludmila] NCI, Lab Translat Genom, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1043-4666
EI 1096-0023
J9 CYTOKINE
JI Cytokine
PD NOV
PY 2015
VL 76
IS 1
MA 87
BP 81
EP 81
DI 10.1016/j.cyto.2015.08.114
PG 1
WC Biochemistry & Molecular Biology; Cell Biology; Immunology
SC Biochemistry & Molecular Biology; Cell Biology; Immunology
GA CS1XO
UT WOS:000361862400111
ER
PT J
AU Pavlakis, GN
Bergamaschi, C
Ng, SM
Chen', S
Bear, J
Alicea, C
Nagy, B
Sowder, R
Chertova, E
Felber, BK
AF Pavlakis, George N.
Bergamaschi, Cristina
Ng, Sin-Man
Chen', Stephanie
Bear, Jenifer
Alicea, Candido
Nagy, Bethany
Sowder, Raymond
Chertova, Elena
Felber, Barbara K.
TI Identification, function and clinical development of the heterodimeric
IL-15 cytokine (hetIL-15)
SO CYTOKINE
LA English
DT Meeting Abstract
CT 3rd Annual Meeting of the International-Cytokine-and-Interferon-Society
(ICIS)
CY OCT 11-14, 2015
CL Bamberg, GERMANY
SP Int Cytokine & Interferon Soc
C1 [Pavlakis, George N.; Bergamaschi, Cristina; Ng, Sin-Man; Chen', Stephanie; Bear, Jenifer; Alicea, Candido; Nagy, Bethany; Felber, Barbara K.] NCI, Frederick, MD 21701 USA.
[Sowder, Raymond; Chertova, Elena] Leidos Biomed Res Inc, AIDS & Canc Virus Program, Frederick Natl Lab Canc Res, Frederick, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1043-4666
EI 1096-0023
J9 CYTOKINE
JI Cytokine
PD NOV
PY 2015
VL 76
IS 1
MA 99
BP 83
EP 84
DI 10.1016/j.cyto.2015.08.126
PG 2
WC Biochemistry & Molecular Biology; Cell Biology; Immunology
SC Biochemistry & Molecular Biology; Cell Biology; Immunology
GA CS1XO
UT WOS:000361862400123
ER
PT J
AU Balinsky, CA
Schmeisser, H
Ganesan, S
Jin, TC
Singh, K
Zoon, KC
AF Balinsky, Corey A.
Schmeisser, Hana
Ganesan, Sundar
Jin, Tengchuan
Singh, Kavita
Zoon, Kathryn C.
TI Characterization of a novel interferon stimulated gene with antiviral
activity against dengue virus
SO CYTOKINE
LA English
DT Meeting Abstract
CT 3rd Annual Meeting of the International-Cytokine-and-Interferon-Society
(ICIS)
CY OCT 11-14, 2015
CL Bamberg, GERMANY
SP Int Cytokine & Interferon Soc
C1 [Balinsky, Corey A.; Schmeisser, Hana; Zoon, Kathryn C.] NIAID, Cytokine Biol Sect, NIH, Bethesda, MD 20892 USA.
[Ganesan, Sundar] NIAID, Biol Imaging Sect, Res Technol Branch, NIH, Bethesda, MD 20892 USA.
[Jin, Tengchuan] NIAID, Struct Immunobiol Unit, NIH, Bethesda, MD 20892 USA.
[Singh, Kavita] NIAID, Struct Biol Unit, Res Technol Branch, NIH, Bethesda, MD 20892 USA.
NR 0
TC 1
Z9 1
U1 1
U2 8
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1043-4666
EI 1096-0023
J9 CYTOKINE
JI Cytokine
PD NOV
PY 2015
VL 76
IS 1
MA 112
BP 86
EP 86
DI 10.1016/j.cyto.2015.08.139
PG 1
WC Biochemistry & Molecular Biology; Cell Biology; Immunology
SC Biochemistry & Molecular Biology; Cell Biology; Immunology
GA CS1XO
UT WOS:000361862400136
ER
PT J
AU Ozato, K
Gupta, M
Sarai, N
Morse, H
Platanias, L
Xiong, HB
Bachu, M
AF Ozato, Keiko
Gupta, Monica
Sarai, Naoyuki
Morse, Herbert
Platanias, Leonidas
Xiong, Huabao
Bachu, Mahesh
TI Chromatin exchange in macrophages and IRF8 dependent autophagy
SO CYTOKINE
LA English
DT Meeting Abstract
CT 3rd Annual Meeting of the International-Cytokine-and-Interferon-Society
(ICIS)
CY OCT 11-14, 2015
CL Bamberg, GERMANY
SP Int Cytokine & Interferon Soc
C1 [Ozato, Keiko; Gupta, Monica; Sarai, Naoyuki; Morse, Herbert; Bachu, Mahesh] NIH, Bethesda, MD USA.
[Platanias, Leonidas] Northwestern Univ, Evanston, IL 60208 USA.
[Xiong, Huabao] Mt Sinai Sch Med, Evanston, IL 60208 USA.
NR 2
TC 0
Z9 0
U1 0
U2 1
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1043-4666
EI 1096-0023
J9 CYTOKINE
JI Cytokine
PD NOV
PY 2015
VL 76
IS 1
MA 211
BP 103
EP 103
DI 10.1016/j.cyto.2015.08.215
PG 1
WC Biochemistry & Molecular Biology; Cell Biology; Immunology
SC Biochemistry & Molecular Biology; Cell Biology; Immunology
GA CS1XO
UT WOS:000361862400212
ER
PT J
AU De Andrea, M
Lo Cigno, I
Albertini, S
Borgogna, C
Peretti, A
Johnson, K
Chandran, B
Landolfo, S
Gariglio, M
AF De Andrea, Marco
Lo Cigno, Irene
Albertini, Silvia
Borgogna, Cinzia
Peretti, Alberto
Johnson, Karen
Chandran, Bala
Landolfo, Santo
Gariglio, Marisa
TI The nuclear Interferon-inducible IFI16 protein and the innate sensing to
HPV18 replication
SO CYTOKINE
LA English
DT Meeting Abstract
CT 3rd Annual Meeting of the International-Cytokine-and-Interferon-Society
(ICIS)
CY OCT 11-14, 2015
CL Bamberg, GERMANY
SP Int Cytokine & Interferon Soc
C1 [De Andrea, Marco; Lo Cigno, Irene; Landolfo, Santo] Turin Med Sch, Viral Pathogenesis Unit, Turin, Italy.
[De Andrea, Marco; Albertini, Silvia; Borgogna, Cinzia; Gariglio, Marisa] Novara Med Sch, Virol Unit, Novara, Italy.
[Peretti, Alberto] NCI, Bethesda, MD 20892 USA.
[Johnson, Karen; Chandran, Bala] Rosalind Franklin Univ Med & Sci, Chicago Med Sch, N Chicago, IL USA.
NR 0
TC 1
Z9 1
U1 0
U2 1
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1043-4666
EI 1096-0023
J9 CYTOKINE
JI Cytokine
PD NOV
PY 2015
VL 76
IS 1
MA 216
BP 104
EP 104
DI 10.1016/j.cyto.2015.08.220
PG 1
WC Biochemistry & Molecular Biology; Cell Biology; Immunology
SC Biochemistry & Molecular Biology; Cell Biology; Immunology
GA CS1XO
UT WOS:000361862400217
ER
PT J
AU Waldmann, TA
AF Waldmann, Thomas A.
TI IL-15 markedly augmented the number of circulating NK cells and enhanced
ADCC mediated by tumor-directed monoclonal antibodies
SO CYTOKINE
LA English
DT Meeting Abstract
CT 3rd Annual Meeting of the International-Cytokine-and-Interferon-Society
(ICIS)
CY OCT 11-14, 2015
CL Bamberg, GERMANY
SP Int Cytokine & Interferon Soc
C1 [Waldmann, Thomas A.] NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1043-4666
EI 1096-0023
J9 CYTOKINE
JI Cytokine
PD NOV
PY 2015
VL 76
IS 1
MA 238
BP 108
EP 109
DI 10.1016/j.cyto.2015.08.241
PG 2
WC Biochemistry & Molecular Biology; Cell Biology; Immunology
SC Biochemistry & Molecular Biology; Cell Biology; Immunology
GA CS1XO
UT WOS:000361862400238
ER
PT J
AU Khouri, R
Decanine, D
Silva-Santos, G
Theys, K
Li, GD
Silva, AC
Farre, L
Bittencourt, A
Mangino, M
Roederer, M
Van Weyenbergh, J
AF Khouri, Ricardo
Decanine, Daniele
Silva-Santos, Gilvaneia
Theys, Kristof
Li, Guangdi
Silva, Aline Clara
Farre, Lourdes
Bittencourt, Achilea
Mangino, Massimo
Roederer, Mario
Van Weyenbergh, Johan
TI A functional FAS polymorphism links CD4 T stem cell memory levels and
IFN-induced apoptosis in both healthy controls and Adult T-cell Leukemia
patients
SO CYTOKINE
LA English
DT Meeting Abstract
CT 3rd Annual Meeting of the International-Cytokine-and-Interferon-Society
(ICIS)
CY OCT 11-14, 2015
CL Bamberg, GERMANY
SP Int Cytokine & Interferon Soc
C1 [Khouri, Ricardo; Theys, Kristof; Li, Guangdi; Van Weyenbergh, Johan] Katholieke Univ Leuven, Dept Microbiol & Immunol, Leuven, Belgium.
[Khouri, Ricardo; Decanine, Daniele; Silva-Santos, Gilvaneia; Silva, Aline Clara; Farre, Lourdes; Van Weyenbergh, Johan] CPqGM FIOCRUZ, Salvador, BA, Brazil.
[Bittencourt, Achilea] HUPES UFBA, Salvador, BA, Brazil.
[Mangino, Massimo] Kings Coll London, Dept Twin Res & Genet Epidemiol, London WC2R 2LS, England.
[Roederer, Mario] NIAID, ImmunoTechnol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
RI Van Weyenbergh, Johan/B-4187-2009; mangino, massimo/F-5134-2011
OI Van Weyenbergh, Johan/0000-0003-3234-8426; mangino,
massimo/0000-0002-2167-7470
NR 0
TC 0
Z9 0
U1 0
U2 3
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1043-4666
EI 1096-0023
J9 CYTOKINE
JI Cytokine
PD NOV
PY 2015
VL 76
IS 1
MA 239
BP 109
EP 109
DI 10.1016/j.cyto.2015.08.242
PG 1
WC Biochemistry & Molecular Biology; Cell Biology; Immunology
SC Biochemistry & Molecular Biology; Cell Biology; Immunology
GA CS1XO
UT WOS:000361862400239
ER
PT J
AU Sabanayagam, C
Lye, WK
Klein, R
Klein, BEK
Cotch, MF
Wang, JJ
Mitchell, P
Shaw, JE
Selvin, E
Sharrett, AR
Wong, TY
AF Sabanayagam, Charumathi
Lye, Weng Kit
Klein, Ronald
Klein, Barbara E. K.
Cotch, Mary Frances
Wang, Jie Jin
Mitchell, Paul
Shaw, Jonathan E.
Selvin, Elizabeth
Sharrett, A. Richey
Wong, Tien Y.
TI Retinal microvascular calibre and risk of diabetes mellitus: a
systematic review and participant-level meta-analysis
SO DIABETOLOGIA
LA English
DT Review
DE Cohort studies; Diabetes; Meta-analysis; Retinal vessels; Systematic
review
ID IMPAIRED FASTING GLUCOSE; LIFE-STYLE AUSDIAB; BEAVER DAM EYE; VASCULAR
CALIBER; INSULIN-RESISTANCE; ENDOTHELIAL DYSFUNCTION; ATHEROSCLEROSIS
RISK; VESSEL DIAMETERS; ARTERIOLAR; MUSCLE
AB Aims/hypothesis The calibre of the retinal vessels has been linked to diabetes mellitus but studies have not shown consistent results. We conducted a participant-level meta-analysis to evaluate the association between retinal arteriolar and venular calibre and diabetes.
Methods We performed a systematic review on MEDLINE and EMBASE for articles published up to December 2014. We identified five population-based prospective cohort studies that provided individual-level data on 18,771 diabetes-free participants. We used discrete time proportional hazards models to estimate pooled HRs of diabetes associated with 1 SD (20 mu m) change in retinal vascular calibre.
Results We identified 2,581 incident cases of diabetes over a median follow-up period of 10 years (interquartile interval of 3.4-15.8 years). After adjustment for demographic, lifestyle and clinical factors, retinal venular calibre was significantly associated with incident diabetes (pooled HR 1.09 [95% CI 1.02, 1.15] per SD increase in venular calibre). This association persisted in analyses excluding individuals with < 5 years of follow-up (1.07 [1.0, 1.12]) or those with impaired fasting glucose at baseline (1.10 [1.03, 1.17]); in subgroup analyses, the association was stronger in men than in women but was consistent across subgroups of race/ethnicity, smoking status, hypertension and BMI categories. Retinal arteriolar calibre was not associated with diabetes (0.95 [0.86, 1.06] per SD decrease in arteriolar calibre).
Conclusions/interpretation Wider retinal venules but not narrower retinal arterioles were associated with a modestly increased risk for diabetes. Knowledge of pathological mechanisms underlying wider retinal venule may provide further insights concerning microvascular alterations in diabetes.
C1 [Sabanayagam, Charumathi; Wong, Tien Y.] Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore 168751, Singapore.
[Sabanayagam, Charumathi; Wong, Tien Y.] Duke NUS Grad Med Sch, Ophthalmol & Visual Sci Acad Clin Program, Singapore, Singapore.
[Sabanayagam, Charumathi; Wong, Tien Y.] Natl Univ Singapore, Dept Ophthalmol, Singapore 117548, Singapore.
[Lye, Weng Kit] Duke NUS Grad Med Sch, Ctr Quantitat Med, Singapore, Singapore.
[Klein, Ronald; Klein, Barbara E. K.] Univ Wisconsin, Dept Ophthalmol & Visual Sci, Sch Med & Publ Hlth, Madison, WI USA.
[Cotch, Mary Frances] NEI, Div Epidemiol & Clin Applicat, NIH, Bethesda, MD 20892 USA.
[Wang, Jie Jin; Mitchell, Paul] Univ Sydney, Ctr Vis Res, Dept Ophthalmol, Sydney, NSW 2006, Australia.
[Wang, Jie Jin; Mitchell, Paul] Univ Sydney, Ctr Vis Res, Westmead Millennium Inst, Sydney, NSW 2006, Australia.
[Shaw, Jonathan E.] Baker IDI Heart & Diabet Inst, Melbourne, Vic, Australia.
[Selvin, Elizabeth; Sharrett, A. Richey] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
RP Wong, TY (reprint author), Singapore Natl Eye Ctr, Singapore Eye Res Inst, 11 Third Hosp Ave, Singapore 168751, Singapore.
EM ophwty@nus.edu.sg
OI Sabanayagam, Charumathi/0000-0002-4042-4719; Cotch, Mary
Frances/0000-0002-2046-4350
FU National Heart, Lung, and Blood Institute [HHSN268201100005C,
HHSN268201100006C, HHSN268201100007C, HHSN268201100008C,
HHSN268201100009C, HHSN268201100010C, HHSN268201100011C,
HHSN268201100012C, N01-HC-95159, N01-HC-95165]; NIH Intramural Research
award from the National Eye Institute, USA [ZIAEY000403]; National
Health and Medical Research Council [350448, 233200]; Sylvia and Charles
Viertel Charitable Foundation; National Eye Institute, National
Institutes of Health Grant [EY-06594]; Research to Prevent Blindness,
New York, NY, USA; Australian National Health & Medical Research
Council; National Medical Research Council, Singapore [STaR/0003/2008,
CG/SERI/2010]
FX We used restricted access datasets of the ARIC study and MESA. The 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). MESA was supported by contracts N01-HC-95159 through
N01-HC-95165 from the National Heart, Lung and Blood Institute and NIH
Intramural Research award ZIAEY000403 from the National Eye Institute,
USA. This article does not necessarily convey the opinions or views of
the ARIC study, MESA or the National Heart, Lung and Blood Institute.
The AusDiab study was supported by National Health and Medical Research
Council Grants 350448 and 233200, and a Sylvia and Charles Viertel
Charitable Foundation grant. BDES was supported by the National Eye
Institute, National Institutes of Health Grant EY-06594, and by Research
to Prevent Blindness, New York, NY, USA. The BMES was supported by the
Australian National Health & Medical Research Council. The study was
funded by grants from the National Medical Research Council, Singapore
(STaR/0003/2008 and CG/SERI/2010), which had no role in study design,
data analysis or interpretation of results.
NR 41
TC 2
Z9 2
U1 1
U2 9
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0012-186X
EI 1432-0428
J9 DIABETOLOGIA
JI Diabetologia
PD NOV
PY 2015
VL 58
IS 11
BP 2476
EP 2485
DI 10.1007/s00125-015-3717-2
PG 10
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA CS3RR
UT WOS:000361993000003
PM 26232097
ER
PT J
AU Li, GN
Huang, K
Nikolic, D
van Breemen, RB
AF Li, Guannan
Huang, Ke
Nikolic, Dejan
van Breemen, Richard B.
TI High-Throughput Cytochrome P450 Cocktail Inhibition Assay for Assessing
Drug-Drug and Drug-Botanical Interactions
SO DRUG METABOLISM AND DISPOSITION
LA English
DT Article
ID TANDEM MASS-SPECTROMETRY; HUMAN LIVER-MICROSOMES; IN-VITRO COCKTAIL;
ENZYMES; METABOLISM; ISOFORMS; P450S; GOLDENSEAL; RUN
AB Detection of drug-drug interactions is essential during the early stages of drug discovery and development, and the understanding of drug-botanical interactions is important for the safe use of botanical dietary supplements. Among the different forms of drug interactions that are known, inhibition of cytochrome P450 (P450) enzymes is the most common cause of drug-drug or drug-botanical interactions. Therefore, a rapid and comprehensive mass spectrometry-based in vitro high-throughput P450 cocktail inhibition assay was developed that uses 10 substrates simultaneously against nine CYP isoforms. Including probe substrates for CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and two probes targeting different binding sites of CYP3A4/5, this cocktail simultaneously assesses at least as many P450 enzymes as previous assays while remaining among the fastest due to short incubation times and rapid analysis using ultrahigh pressure liquid chromatography-tandem mass spectrometry. The method was validated using known inhibitors of each P450 enzyme and then shown to be useful not only for single-compound testing but also for the evaluation of potential drug-botanical interactions using the botanical dietary supplement licorice (Glycyrrhiza glabra) as an example.
C1 [Li, Guannan; Huang, Ke; Nikolic, Dejan; van Breemen, Richard B.] Univ Illinois, Coll Pharm, Dept Med Chem & Pharmacognosy, NIH,Ctr Bot Dietary Supplements Res, Chicago, IL 60612 USA.
RP van Breemen, RB (reprint author), Univ Illinois, Coll Pharm, Dept Med Chem & Pharmacognosy, 833 S Wood St, Chicago, IL 60612 USA.
EM breemen@uic.edu
OI Li, Guannan/0000-0002-9533-7524
FU National Institutes of Health Office of Dietary Supplements [P50
AT000155]; National Center for Complementary and Integrative Health [P50
AT000155, R01 AT007659]
FX This work was supported by the National Institutes of Health Office of
Dietary Supplements [Grant P50 AT000155] and the National Center for
Complementary and Integrative Health [Grants P50 AT000155 and R01
AT007659].
NR 41
TC 4
Z9 4
U1 1
U2 16
PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA
SN 0090-9556
EI 1521-009X
J9 DRUG METAB DISPOS
JI Drug Metab. Dispos.
PD NOV
PY 2015
VL 43
IS 11
BP 1670
EP 1678
DI 10.1124/dmd.115.065987
PG 9
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA CS5JC
UT WOS:000362113300004
PM 26285764
ER
PT J
AU Starling, AP
Engel, LS
Calafat, AM
Koutros, S
Satagopan, JM
Yang, G
Matthews, CE
Cai, QY
Buckley, JP
Ji, BT
Cai, H
Chow, WH
Zheng, W
Gao, YT
Rothman, N
Xiang, YB
Shu, XO
AF Starling, Anne P.
Engel, Lawrence S.
Calafat, Antonia M.
Koutros, Stella
Satagopan, Jaya M.
Yang, Gong
Matthews, Charles E.
Cai, Qiuyin
Buckley, Jessie P.
Ji, Bu-Tian
Cai, Hui
Chow, Wong-Ho
Zheng, Wei
Gao, Yu-Tang
Rothman, Nathaniel
Xiang, Yong-Bing
Shu, Xiao-Ou
TI Predictors and long-term reproducibility of urinary phthalate
metabolites in middle-aged men and women living in urban Shanghai
SO ENVIRONMENT INTERNATIONAL
LA English
DT Article
DE Phthalates; Reproducibility; Predictors; Food contaminants; Personal
care products
ID NUTRITION EXAMINATION SURVEY; HUMAN EXPOSURE; BISPHENOL-A; TEMPORAL
VARIABILITY; NATIONAL-HEALTH; US POPULATION; UNITED-STATES; CHINA;
ESTERS; MEDICATIONS
AB Phthalate esters are man-made chemicals commonly used as plasticizers and solvents, and humans may be exposed through ingestion, inhalation, and dermal absorption. Little is known about predictors of phthalate exposure, particularly in Asian countries. Because phthalates are rapidly metabolized and excreted from the body following exposure, it is important to evaluate whether phthalate metabolites measured at a single point in time can reliably rank exposures to phthalates over a period of time. We examined the concentrations and predictors of phthalate metabolite concentrations among 50 middle-aged women and 50 men from two Shanghai cohorts, enrolled in 1997-2000 and 2002-2006, respectively. We assessed the reproducibility of urinary concentrations of phthalate metabolites in three spot samples per participant taken several years apart (mean interval between first and third sample was 7.5 years [women] or 2.9 years [men]), using Spearman's rank correlation coefficients and intra-class correlation coefficients. We detected ten phthalate metabolites in at least 50% of individuals for two or more samples. Participant sex, age, menopausal status, education, income, body mass index, consumption of bottled water, recent intake of medication, and time of day of collection of the urine sample were associated with concentrations of certain phthalate metabolites. The reproducibility of an individual's urinary concentration of phthalate metabolites across several years was low, with all intra-class correlation coefficients and most Spearman rank correlation coefficients <= 03. Only mono(2-ethylhexyl) phthalate, a metabolite of di(2-ethylhexyl) phthalate, had a Spearman rank correlation coefficient >= 0.4 among men, suggesting moderate reproducibility. These findings suggest that a single spot urine sample is not sufficient to rank exposures to phthalates over several years in an adult urban Chinese population. Published by Elsevier Ltd.
C1 [Starling, Anne P.; Engel, Lawrence S.; Buckley, Jessie P.] Univ N Carolina, Dept Epidemiol, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA.
[Calafat, Antonia M.] Ctr Dis Control & Prevent, Div Sci Lab, Natl Ctr Environm Hlth, Atlanta, GA USA.
[Koutros, Stella; Matthews, Charles E.; Ji, Bu-Tian; Chow, Wong-Ho; Rothman, Nathaniel] NCI, Div Canc Epidemiol & Genet, NIH, US Dept HHS, Bethesda, MD 20892 USA.
[Satagopan, Jaya M.] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA.
[Yang, Gong; Cai, Qiuyin; Cai, Hui; Zheng, Wei; Shu, Xiao-Ou] Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Div Epidemiol,Dept Med,Vanderbilt Epidemiol Ctr, Nashville, TN 37212 USA.
[Gao, Yu-Tang] Shanghai Jiao Tong Univ, Shanghai Canc Inst, Dept Epidemiol, Shanghai 200030, Peoples R China.
[Xiang, Yong-Bing] Shanghai Jiao Tong Univ, Sch Med, Renji Hosp, Shanghai Canc Inst, Shanghai 200030, Peoples R China.
RP Starling, AP (reprint author), Univ Colorado, Dept Epidemiol, Colorado Sch Publ Hlth, Anschutz Med Campus,Campus Box F426,12474 E 19th, Aurora, CO 80045 USA.
EM Anne.Starling@ucdenver.edu
OI Satagopan, Jaya/0000-0001-7102-5633; Engel, Lawrence/0000-0001-9268-4830
FU National Institutes of Health; National Cancer Institute Division of
Cancer Epidemiology and Genetics; National Cancer Institute [R37
CA070867, UM1182910, UM1 CA173640, NO2-CP11010-66]; National Institutes
of Health from National Cancer Institute [R01CA137420]; Cancer Center
Core Grant from the National Cancer Institute [P30CA008748]; Clinical
and Translational Science Center at Weill Cornell Medical College, New
York, USA [UL1RR024996]
FX Funding sources: The study was funded in part by the Intramural Research
Program of the National Institutes of Health and the National Cancer
Institute Division of Cancer Epidemiology and Genetics. Support for the
Shanghai Women's Health Study (R37 CA070867, UM1182910, PI: Zheng), the
Shanghai Men's Health Study (UM1 CA173640, PI: Shu) and the physical
activity substudy (NO2-CP11010-66, PI: Shu) was provided by grants from
the National Cancer Institute. Dr. Satagopan was supported by the
following grants from the National Institutes of Health: R01CA137420,
Cancer Center Core Grant P30CA008748 from the National Cancer Institute,
and UL1RR024996 from the Clinical and Translational Science Center at
Weill Cornell Medical College, New York, USA
NR 46
TC 4
Z9 4
U1 5
U2 20
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0160-4120
EI 1873-6750
J9 ENVIRON INT
JI Environ. Int.
PD NOV
PY 2015
VL 84
BP 94
EP 106
DI 10.1016/j.envint.2015.07.003
PG 13
WC Environmental Sciences
SC Environmental Sciences & Ecology
GA CS5UK
UT WOS:000362143600011
PM 26255822
ER
PT J
AU Giesel, FL
Fiedler, H
Stefanova, M
Sterzing, F
Rius, M
Kopka, K
Moltz, JH
Afshar-Oromieh, A
Choyke, PL
Haberkorn, U
Kratochwil, C
AF Giesel, Frederik L.
Fiedler, H.
Stefanova, M.
Sterzing, F.
Rius, M.
Kopka, K.
Moltz, J. H.
Afshar-Oromieh, A.
Choyke, P. L.
Haberkorn, U.
Kratochwil, C.
TI PSMA PET/CT with Glu-urea-Lys-(Ahx)-[Ga-68(HBED-CC)] versus 3D CT
volumetric lymph node assessment in recurrent prostate cancer
SO EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING
LA English
DT Article
DE Ga-68-PSMA-11 PET/CT; Recurrent prostate cancer; Lymph node evaluation;
Lymph node metastasis
ID MEMBRANE ANTIGEN; COMPUTERIZED-TOMOGRAPHY; ANDROGEN RECEPTOR;
METASTASES; DISSECTION; DIAGNOSIS; THERAPY; LIGAND; MRI
AB Purpose PET/CT with the PSMA ligand is a powerful new method for the early detection of nodal metastases in patients with biochemical relapse. The purpose of this retrospective investigation was to evaluate the volume and dimensions of nodes identified by Glu-urea-Lys-(Ahx)-[Ga-68(HBED-CC)] (Ga-68-PSMA-11) in the setting of recurrent prostate cancer.
Methods All PET/CT images were acquired 60 +/- 10 min after intravenous injection of Ga-68-PSMA-11 (mean dose 176 MBq). In 21 patients with recurrent prostate cancer and rising PSA, 49 PSMA-positive lymph nodes were identified. Using semiautomated lymph node segmentation software, node volume and short-axis and long-axis dimensions were measured and compared with the maximum standardized uptake values (SUVmax). Round nodes greater than or equal to 8 mm were considered positive by morphological criteria alone. The percentage of nodes identified by elevated SUVmax but not by conventional morphological criteria was determined.
Results The mean volume of Ga-68-PSMA-11-positive nodes was 0.5 ml (range 0.2 - 2.3 ml), and the mean short-axis diameter was 5.8 mm (range 2.4 - 13.3 mm). In 7 patients (33.3 %) with 31 PSMA-positive nodes only 11 (36 %) were morphologically positive based on diameters > 8 mm on CT. In the remaining 14 patients (66.7 %), 18 (37 %) of PSMA positive lymph nodes had short-axis diameters < 8 mm with a mean short-axis diameter of 5.0 mm (range 2.4 - 7.9 mm). Thus, in this population, Ga-68-PSMA-11 PET/CT detected nodal recurrence in two-thirds of patients who would have been missed using conventional morphological criteria.
Conclusion Ga-68-PSMA-11 PET/CT is more sensitive than CT based 3D volumetric lymph node evaluation in determining the node status of patients with recurrent prostate cancer, and is a promising method of restaging prostate cancers in this setting.
C1 [Giesel, Frederik L.; Fiedler, H.; Stefanova, M.; Afshar-Oromieh, A.; Haberkorn, U.; Kratochwil, C.] Heidelberg Univ, Dept Nucl Med, Univ Heidelberg Hosp, INF 400, D-69120 Heidelberg, Germany.
[Sterzing, F.] Heidelberg Univ, Dept RadioOncol, D-69120 Heidelberg, Germany.
[Rius, M.] European Commiss, Inst Transuranium Elements ITU, Karlsruhe, Germany.
[Kopka, K.; Moltz, J. H.] German Canc Res Ctr, Radiopharmaceut Chem, Heidelberg, Germany.
[Choyke, P. L.] NCI, Mol Imaging Program, Bethesda, MD 20892 USA.
[Giesel, Frederik L.; Rius, M.; Haberkorn, U.] DKFZ, Cooperat Unit Nucl Med, Heidelberg, Germany.
RP Giesel, FL (reprint author), Heidelberg Univ, Dept Nucl Med, Univ Heidelberg Hosp, INF 400, D-69120 Heidelberg, Germany.
EM frederik@egiesel.com
FU Klaus-Tschira-Stiftung [00.198.2012]
FX This research was supported by the Klaus-Tschira-Stiftung (project no.
00.198.2012).
NR 26
TC 25
Z9 25
U1 2
U2 11
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1619-7070
EI 1619-7089
J9 EUR J NUCL MED MOL I
JI Eur. J. Nucl. Med. Mol. Imaging
PD NOV
PY 2015
VL 42
IS 12
BP 1794
EP 1800
DI 10.1007/s00259-015-3106-6
PG 7
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA CS3TJ
UT WOS:000361997600003
PM 26162799
ER
PT J
AU Saporito, RA
Norton, RA
Garraffo, MH
Spande, TF
AF Saporito, Ralph A.
Norton, Roy A.
Garraffo, Martin H.
Spande, Thomas F.
TI Taxonomic distribution of defensive alkaloids in Nearctic oribatid mites
(Acari, Oribatida)
SO EXPERIMENTAL AND APPLIED ACAROLOGY
LA English
DT Article
DE Chemical defense; Dendrobatids; Opisthonotal (oil) gland; Poison frogs;
Soil mites; Scheloribates; Protokalumma
ID POISON FROGS; CHEMICAL DEFENSE; SKIN ALKALOIDS; ANURA; DIET; MECHANISMS;
BUFONIDAE; EVOLUTION; TOXICITY
AB The opisthonotal (oil) glands of oribatid mites are the source of a wide diversity of taxon-specific defensive chemicals, and are likely the location for the more than 90 alkaloids recently identified in oribatids. Although originally recognized in temperate oribatid species, alkaloids have also been detected in related lineages of tropical oribatids. Many of these alkaloids are also present in a worldwide radiation of poison frogs, which are known to sequester these defensive chemicals from dietary arthropods, including oribatid mites. To date, most alkaloid records involve members of the superfamily Oripodoidea (Brachypylina), although few species have been examined and sampling of other taxonomic groups has been highly limited. Herein, we examined adults of more than 60 species of Nearctic oribatid mites, representing 46 genera and 33 families, for the presence of alkaloids. GC-MS analyses of whole body extracts led to the detection of 15 alkaloids, but collectively they occur only in members of the genera Scheloribates (Scheloribatidae) and Protokalumma (Parakalummidae). Most of these alkaloids have also been detected previously in the skin of poison frogs. All examined members of the oripodoid families Haplozetidae and Oribatulidae were alkaloid-free, and no mites outside the Oripodoidea contained alkaloids. Including previous studies, all sampled species of the cosmopolitan oripodoid families Scheloribatidae and Parakalummidae, and the related, mostly tropical families Mochlozetidae and Drymobatidae contain alkaloids. Our findings are consistent with a generalization that alkaloid presence is widespread, but not universal in Oripodoidea. Alkaloid presence in tropical, but not temperate members of some non-oripodoid taxa (in particular Galumnidae) deserves further study.
C1 [Saporito, Ralph A.] John Carroll Univ, Dept Biol, University Hts, OH 44118 USA.
[Norton, Roy A.] SUNY Coll Environm Sci & Forestry, Syracuse, NY 13210 USA.
[Garraffo, Martin H.] NIDDK, DHHS, Clin Mass Spectrometry Core, NIH, Bethesda, MD 20892 USA.
[Spande, Thomas F.] NIDA, DHHS, Med Chem Lab, NIH, Bethesda, MD 20892 USA.
RP Saporito, RA (reprint author), John Carroll Univ, Dept Biol, University Hts, OH 44118 USA.
EM rsaporito@jcu.edu
FU NIDDK; John Carroll University (JCU); Kresge Challenge Grant
FX This study was supported by intramural funds of NIDDK, John Carroll
University (JCU), and a Kresge Challenge Grant awarded to JCU. We thank
Dr. Michael A. Nichols for his assistance in maintaining the GC-MS, and
Dr. Valerie Behan-Pelletier for taxonomic advice on the identity of
Ceratozetes species.
NR 46
TC 4
Z9 4
U1 2
U2 8
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0168-8162
EI 1572-9702
J9 EXP APPL ACAROL
JI Exp. Appl. Acarol.
PD NOV
PY 2015
VL 67
IS 3
BP 317
EP 333
DI 10.1007/s10493-015-9962-8
PG 17
WC Entomology
SC Entomology
GA CS8FI
UT WOS:000362321000001
PM 26264156
ER
PT J
AU Gooskens, SL
Gadd, S
Auvil, JG
Gerhard, DS
Khan, J
Patidar, R
Meerzaman, D
Chen, QR
Hsu, CH
Yan, C
Nguyen, C
Hu, Y
Mullighan, CG
Ma, J
de Krijger, R
van den Heuvel-Eibrink, MM
Smith, MA
Ross, N
Gastier-Foster, JM
Perlman, EJ
AF Gooskens, S. L.
Gadd, S.
Auvil, J. Guidry
Gerhard, D. S.
Khan, J.
Patidar, R.
Meerzaman, D.
Chen, Q. R.
Hsu, C. H.
Yan, C.
Nguyen, C.
Hu, Y.
Mullighan, C. G.
Ma, J.
de Krijger, R.
van den Heuvel-Eibrink, M. M.
Smith, M. A.
Ross, N.
Gastier-Foster, J. M.
Perlman, E. J.
TI TCF21 IS HYPERMETHYLATED IN CLEAR CELL SARCOMA OF THE KIDNEY: A
GENOME-WIDE TARGET STUDY
SO PEDIATRIC BLOOD & CANCER
LA English
DT Meeting Abstract
C1 [Gooskens, S. L.] Erasmus MC Sophia Childrens Hosp, Dept Pediat Hematol & Oncol, Rotterdam, Netherlands.
[Gadd, S.; Perlman, E. J.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA.
[Gadd, S.; Perlman, E. J.] Robert H Lurie Canc Ctr, Dept Pathol, Chicago, IL USA.
[Auvil, J. Guidry; Gerhard, D. S.] NCI, Off Canc Genom, Bethesda, MD 20892 USA.
[Khan, J.; Patidar, R.] Oncogen Sect, Genet Branch, Bethesda, MD USA.
[Meerzaman, D.; Chen, Q. R.; Hsu, C. H.; Yan, C.; Nguyen, C.; Hu, Y.] NCI, NIH, Ctr Biomed Informat & Informat Technol, Bethesda, MD 20892 USA.
[Mullighan, C. G.; Ma, J.] St Jude Childrens Res Hosp, Dept Pathol, Memphis, TN 38105 USA.
[de Krijger, R.] Erasmus MC, Josephine Nefkens Inst, Dept Pathol, Rotterdam, Netherlands.
[van den Heuvel-Eibrink, M. M.] Princess Maxima Ctr Pediat Oncol, Dept Pediat Oncol, Utrecht, Netherlands.
[Smith, M. A.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
[Ross, N.; Gastier-Foster, J. M.] Ohio State Univ, Coll Med, Nationwide Childrens Hosp, Dept Pathol & Lab Med, Columbus, OH 43210 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1545-5009
EI 1545-5017
J9 PEDIATR BLOOD CANCER
JI Pediatr. Blood Cancer
PD NOV
PY 2015
VL 62
SU 4
MA O-117
BP S176
EP S176
PG 1
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA CR3QE
UT WOS:000361247200118
ER
PT J
AU Gupta, S
Aitken, J
Bartels, U
Brierley, J
Dolendo, M
Friedrich, P
Fuentes, S
Garcia, C
Gatta, G
Gospodarowicz, M
Gross, T
Howard, S
Molyneaux, E
Moreno, F
Pritchard-Jones, K
Pole, J
Ramirez, O
Ries, L
Rodriguez-Galindo, C
Shin, HY
Steliarova-Foucher, E
Sung, L
Supriyadi, E
Swaminathan, R
Torode, J
Vora, T
Kutluk, T
Frazier, AL
AF Gupta, S.
Aitken, J.
Bartels, U.
Brierley, J.
Dolendo, M.
Friedrich, P.
Fuentes, S.
Garcia, C.
Gatta, G.
Gospodarowicz, M.
Gross, T.
Howard, S.
Molyneaux, E.
Moreno, F.
Pritchard-Jones, K.
Pole, J.
Ramirez, O.
Ries, L.
Rodriguez-Galindo, C.
Shin, H. Y.
Steliarova-Foucher, E.
Sung, L.
Supriyadi, E.
Swaminathan, R.
Torode, J.
Vora, T.
Kutluk, T.
Frazier, A. L.
TI CONSENSUS-BASED PRINCIPLES AND CLASSIFICATION SYSTEMS FOR COLLECTING
PAEDIATRIC CANCER STAGE IN POPULATION-BASED CANCER REGISTRIES
SO PEDIATRIC BLOOD & CANCER
LA English
DT Meeting Abstract
C1 [Gupta, S.; Bartels, U.; Sung, L.] Hosp Sick Children, Div Haematol Oncol, Toronto, ON M5G 1X8, Canada.
[Aitken, J.] Canc Care Queensland, Dept Res, Brisbane, Qld, Australia.
[Brierley, J.; Gospodarowicz, M.] Princess Margaret Hosp, Div Radiat Oncol, Toronto, ON M4X 1K9, Canada.
[Dolendo, M.] Davao Med Ctr, Pediat Oncol, Davao, Philippines.
[Friedrich, P.; Rodriguez-Galindo, C.; Frazier, A. L.] Dana Farber Canc Inst, Pediat Hematol Oncol, Boston, MA 02115 USA.
[Fuentes, S.] Hostpital Nacl Ninos Benjamin Bloom, Oncol Serv, San Salvador, El Salvador.
[Garcia, C.] Unidad Nacl Oncol Pediat, Pediat Oncol, Guatemala City, Guatemala.
[Gatta, G.] Ist Nazl Studio & Cura Tumori, Epidemiol Unit, I-20133 Milan, Italy.
[Gross, T.] NCI, Ctr Global Hlth, Bethesda, MD 20892 USA.
[Howard, S.] Univ Tennessee, Coll Med, Memphis, TN USA.
[Molyneaux, E.] Queen Elizabeth Cent Hosp, Dept Pediat, Blantyre, Malawi.
[Moreno, F.] Natl Canc Inst, Paediat Canc Registry, Buenos Aires, DF, Argentina.
[Pritchard-Jones, K.] Kings Coll London, Inst Child Hlth, London WC2R 2LS, England.
[Pole, J.] Pediat Oncol Grp Ontario, POGO Res Unit, Toronto, ON, Canada.
[Ramirez, O.] Univ Valle, Registro Poblac Canc Cali, Cali, Colombia.
[Ries, L.] NCI, SEER Program, Bethesda, MD 20892 USA.
[Shin, H. Y.] Seoul Natl Univ, Childrens Hosp, Pediat Oncol, Seoul, South Korea.
[Steliarova-Foucher, E.] IARC, Canc Informat Sect, Lyon, France.
[Supriyadi, E.] Univ Gadjah Mada, Div Pediat Hematol Oncol, Yogyakarta, Indonesia.
[Swaminathan, R.] Canc Inst WIA, Canc Registry, Madras, Tamil Nadu, India.
[Torode, J.] UICC, Geneva, Switzerland.
[Vora, T.] Tata Mem Hosp, Pediat Med Oncol, Bombay, Maharashtra, India.
[Kutluk, T.] Hacettepe Univ, Sch Med, Pediat Oncol, Ankara, Turkey.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1545-5009
EI 1545-5017
J9 PEDIATR BLOOD CANCER
JI Pediatr. Blood Cancer
PD NOV
PY 2015
VL 62
SU 4
MA O-094
BP S169
EP S170
PG 2
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA CR3QE
UT WOS:000361247200095
ER
PT J
AU Jindal, B
Naredi, BK
Vuriti, M
Rijhwani, A
Chakkalakkoombil, SV
Badhe, BA
Han, JC
Reyes-Capo, D
AF Jindal, B.
Naredi, B. K.
Vuriti, M.
Rijhwani, A.
Chakkalakkoombil, S. V.
Badhe, B. A.
Han, J. C.
Reyes-Capo, D.
TI BILATERAL WILMS' TUMOR (WT) IN A HORSE SHOE KIDNEY WITH WAGR SYNDROME: A
RARE ASSOCIATION
SO PEDIATRIC BLOOD & CANCER
LA English
DT Meeting Abstract
C1 [Jindal, B.; Naredi, B. K.; Vuriti, M.; Rijhwani, A.] Jawaharlal Inst Postgrad Med Educ & Res, Dept Pediat Surg, Pondicherry, India.
[Chakkalakkoombil, S. V.] Jawaharlal Inst Postgrad Med Educ & Res, Dept Radiol, Pondicherry, India.
[Badhe, B. A.] Jawaharlal Inst Postgrad Med Educ & Res, Dept Pathol, Pondicherry, India.
[Han, J. C.; Reyes-Capo, D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Unit Metab & Neuroendocrinol, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1545-5009
EI 1545-5017
J9 PEDIATR BLOOD CANCER
JI Pediatr. Blood Cancer
PD NOV
PY 2015
VL 62
SU 4
MA P-658
BP S397
EP S397
PG 1
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA CR3QE
UT WOS:000361247201490
ER
PT J
AU Lock, R
Houghton, P
Smith, M
AF Lock, R.
Houghton, P.
Smith, M.
TI A REVIEW OF NEW AGENTS TESTED BY THE PEDIATRIC PRECLINICAL TESTING
PROGRAM AGAINST ACUTE LYMPHOBLASTIC LEUKEMIA XENOGRAFTS
SO PEDIATRIC BLOOD & CANCER
LA English
DT Meeting Abstract
C1 [Lock, R.] UNSW Australia, Childrens Canc Inst, Randwick, NSW, Australia.
[Houghton, P.] UT Hlth Sci Ctr, Greehey Childrens Canc Res Inst, San Antonio, TX USA.
[Smith, M.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1545-5009
EI 1545-5017
J9 PEDIATR BLOOD CANCER
JI Pediatr. Blood Cancer
PD NOV
PY 2015
VL 62
SU 4
MA PD-004
BP S211
EP S211
PG 1
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA CR3QE
UT WOS:000361247200258
ER
PT J
AU Raznahan, A
Lue, Y
Probst, F
Greenstein, D
Giedd, J
Wang, C
Lerch, J
Swerdloff, R
AF Raznahan, Armin
Lue, YanHe
Probst, Frank
Greenstein, Deanna
Giedd, Jay
Wang, Christina
Lerch, Jason
Swerdloff, Ronald
TI Triangulating the sexually dimorphic brain through high-resolution
neuroimaging of murine sex chromosome aneuploidies
SO BRAIN STRUCTURE & FUNCTION
LA English
DT Article
DE Brain anatomy; Sexual dimorphism; XO; XXY
ID ORIGIN ALLELIC EXPRESSION; KLINEFELTER-SYNDROME; PERIAQUEDUCTAL GRAY;
TURNER-SYNDROME; X-CHROMOSOME; MOUSE-BRAIN; NEUROPSYCHIATRIC DISORDERS;
STRIA TERMINALIS; SOCIAL-BEHAVIOR; XXY MICE
AB Murine sex chromosome aneuploidies (SCAs) provide powerful models for charting sex chromosome influences on mammalian brain development. Here, building on prior work in X-monosomic (XO) mice, we use spatially non-biased high-resolution imaging to compare and contrast neuroanatomical alterations in XXY and XO mice relative to their wild-type XX and XY littermates. First, we show that carriage of a supernumerary X chromosome in XXY males (1) does not prevent normative volumetric masculinization of the bed nucleus of the stria terminalis (BNST) and medial amygdala, but (2) causes distributed anatomical alterations relative to XY males, which show a statistically unexpected tendency to be co-localized with and reciprocal to XO-XX differences in anatomy. These overlaps identify the lateral septum, BNST, ventral group thalamic nuclei and periaqueductal gray matter as regions with replicable sensitivity to X chromosome dose across two SCAs. We then harness anatomical variation across all four karyotype groups in our study-XO, XX, XY and XXY-to create an agnostic data-driven segmentation of the mouse brain into five distributed clusters which (1) recover fundamental properties of brain organization with high spatial precision, (2) define two previously uncharacterized systems of relative volume excess in females vs. males ("forebrain cholinergic" and "cerebelo-pontine-thalamo-cortical"), and (3) adopt stereotyped spatial motifs which delineate ordered gradients of sex chromosome and gonadal influences on volumetric brain development. Taken together, these data provide a new framework for the study of sexually dimorphic influences on brain development in health and disrupted brain development in SCA.
C1 [Raznahan, Armin; Greenstein, Deanna; Giedd, Jay] NIMH, Child Psychiat Branch, NIH, Bethesda, MD 20815 USA.
[Lue, YanHe; Wang, Christina; Swerdloff, Ronald] Harbor UCLA Med Ctr, Los Angele Biomed Res Inst, Dept Med, Div Endocrinol, Torrance, CA USA.
[Probst, Frank] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA.
[Lerch, Jason] Hosp Sick Children Hosp, Mouse Imaging Ctr, Toronto, ON, Canada.
[Lerch, Jason] Hosp Sick Children Hosp, Program Neurosci & Mental, Toronto, ON, Canada.
RP Raznahan, A (reprint author), NIMH, Child Psychiat Branch, NIH, Rm 4C108,Bldg 20,10 Ctr Dr, Bethesda, MD 20815 USA.
EM raznahana@mail.nih.gov
RI Giedd, Jay/J-9644-2015
OI Giedd, Jay/0000-0003-2002-8978
FU Intramural NIH HHS [Z99 MH999999]
NR 66
TC 2
Z9 2
U1 0
U2 4
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 1863-2653
EI 1863-2661
J9 BRAIN STRUCT FUNCT
JI Brain Struct. Funct.
PD NOV
PY 2015
VL 220
IS 6
BP 3581
EP 3593
DI 10.1007/s00429-014-0875-9
PG 13
WC Anatomy & Morphology; Neurosciences
SC Anatomy & Morphology; Neurosciences & Neurology
GA CR7XS
UT WOS:000361566000031
PM 25146308
ER
PT J
AU Chetty, IJ
Martel, MK
Jaffray, DA
Benedict, SH
Hahn, SM
Berbeco, R
Deye, J
Jeraj, R
Kavanagh, B
Krishnan, S
Lee, N
Low, DA
Mankoff, D
Marks, LB
Ollendorf, D
Paganetti, H
Ross, B
Siochi, RAC
Timmerman, RD
Wong, JW
AF Chetty, Indrin J.
Martel, Mary K.
Jaffray, David A.
Benedict, Stanley H.
Hahn, Stephen M.
Berbeco, Ross
Deye, James
Jeraj, Robert
Kavanagh, Brian
Krishnan, Sunil
Lee, Nancy
Low, Daniel A.
Mankoff, David
Marks, Lawrence B.
Ollendorf, Daniel
Paganetti, Harald
Ross, Brian
Siochi, Ramon Alfredo C.
Timmerman, Robert D.
Wong, John W.
TI Technology for Innovation in Radiation Oncology
SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
LA English
DT Article
ID CELL LUNG-CANCER; FUTURE PERSPECTIVES; GOLD NANOPARTICLES; ION
RADIOTHERAPY; CLINICAL-TRIALS; PROTON-BEAM; THERAPY; RISK; MRI;
IRRADIATION
AB Radiation therapy is an effective, personalized cancer treatment that has benefited from technological advances associated with the growing ability to identify and target tumors with accuracy and precision. Given that these advances have played a central role in the success of radiation therapy as a major component of comprehensive cancer care, the American Society for Radiation Oncology (ASTRO), the American Association of Physicists in Medicine (AAPM), and the National Cancer Institute (NCI) sponsored a workshop entitled "Technology for Innovation in Radiation Oncology," which took place at the National Institutes of Health (NIH) in Bethesda, Maryland, on June 13 and 14, 2013. The purpose of this workshop was to discuss emerging technology for the field and to recognize areas for greater research investment. Expert clinicians and scientists discussed innovative technology in radiation oncology, in particular as to how these technologies are being developed and translated to clinical practice in the face of current and future challenges and opportunities. Technologies encompassed topics in functional imaging, treatment devices, nanotechnology, and information technology. The technical, quality, and safety performance of these technologies were also considered. A major theme of the workshop was the growing importance of innovation in the domain of process automation and oncology informatics. The technologically advanced nature of radiation therapy treatments predisposes radiation oncology research teams to take on informatics research initiatives. In addition, the discussion on technology development was balanced with a parallel conversation regarding the need for evidence of efficacy and effectiveness. The linkage between the need for evidence and the efforts in informatics research was clearly identified as synergistic. (C) 2015 Elsevier Inc. All rights reserved.
C1 [Chetty, Indrin J.] Henry Ford Hosp, Dept Radiat Oncol, Detroit, MI 48202 USA.
[Martel, Mary K.] Univ Texas MD Anderson Canc Ctr, Dept Radiat Phys, Houston, TX 77030 USA.
[Jaffray, David A.] Princess Margaret Hosp, Dept Radiat Oncol, Toronto, ON M4X 1K9, Canada.
[Jaffray, David A.] Princess Margaret Hosp, Dept Med Biophys, Toronto, ON M4X 1K9, Canada.
[Benedict, Stanley H.] Univ Calif Davis, Ctr Canc, Dept Radiat Oncol, Sacramento, CA 95817 USA.
[Hahn, Stephen M.; Krishnan, Sunil] Univ Texas MD Anderson Canc Ctr, Dept Radiat Oncol, Houston, TX 77030 USA.
[Berbeco, Ross] Brigham & Womens Hosp, Dept Radiat Oncol, Boston, MA 02115 USA.
[Deye, James] Natl Canc Inst, Radiat Res Programs, Bethesda, MD USA.
[Jeraj, Robert] Univ Wisconsin, Dept Med Phys, Madison, WI 53706 USA.
[Kavanagh, Brian] Univ Colorado, Dept Radiat Oncol, Aurora, CO USA.
[Lee, Nancy] Mem Sloan Kettering Canc Ctr, Dept Radiat Oncol, New York, NY 10021 USA.
[Low, Daniel A.] Univ Calif Los Angeles, Dept Radiat Oncol, Los Angeles, CA 90024 USA.
[Mankoff, David] Univ Washington, Sch Med, Dept Radiol, Seattle, WA USA.
[Marks, Lawrence B.] Univ North Carolina Hosp, Dept Radiat Oncol, Chapel Hill, NC USA.
[Ollendorf, Daniel] Inst Clin & Econ Review, Boston, MA USA.
[Paganetti, Harald] Proton Therapy Ctr, Dept Radiat Oncol, Massachusetts Gen Hosp, Boston, MA USA.
[Ross, Brian] Univ Michigan Hlth Syst, Dept Radiol, Ann Arbor, MI USA.
[Siochi, Ramon Alfredo C.] W Virginia Univ, Dept Radiat Oncol, Morgantown, WV 26506 USA.
[Timmerman, Robert D.] Univ Texas SW Med Ctr Dallas, Dept Radiat Oncol, Dallas, TX 75390 USA.
[Wong, John W.] Johns Hopkins Univ, Dept Radiat Oncol, Baltimore, MD USA.
RP Martel, MK (reprint author), Univ Texas MD Anderson Canc Ctr, Dept Radiat Phys, Houston, TX 77030 USA.
EM mmartel@mdanderson.org
FU American Society for Radiation Oncology; American Association of
Physicists in Medicine
FX The authors thank the National Cancer Institute for their support of the
meeting in providing resources and hosting the meeting at the National
Institutes of Health. They also thank the American Society for Radiation
Oncology and the American Association of Physicists in Medicine for
their financial assistance, without which this meeting would not have
been possible.
NR 54
TC 7
Z9 7
U1 3
U2 40
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0360-3016
EI 1879-355X
J9 INT J RADIAT ONCOL
JI Int. J. Radiat. Oncol. Biol. Phys.
PD NOV 1
PY 2015
VL 93
IS 3
BP 485
EP 492
DI 10.1016/j.ijrobp.2015.07.007
PG 8
WC Oncology; Radiology, Nuclear Medicine & Medical Imaging
SC Oncology; Radiology, Nuclear Medicine & Medical Imaging
GA CS2ED
UT WOS:000361879700003
PM 26460989
ER
PT J
AU Palmer, NRA
Weaver, KE
Hauser, SP
Lawrence, JA
Talton, J
Case, LD
Geiger, AM
AF Palmer, Nynikka R. A.
Weaver, Kathryn E.
Hauser, Sally P.
Lawrence, Julia A.
Talton, Jennifer
Case, L. Douglas
Geiger, Ann M.
TI Disparities in barriers to follow-up care between African American and
White breast cancer survivors
SO SUPPORTIVE CARE IN CANCER
LA English
DT Article
DE Barriers; Follow-up care; Health disparities; Cancer survivor; Breast
cancer
ID UNITED-STATES; NONCANCER CONTROLS; MEDICAL-CARE; PATIENT; SURVEILLANCE;
METAANALYSIS; DIAGNOSIS; SUPPORT; ACCESS; SYSTEM
AB Despite recommendations for breast cancer survivorship care, African American women are less likely to receive appropriate follow-up care, which is concerning due to their higher mortality rates. This study describes differences in barriers to follow-up care between African American and White breast cancer survivors.
We conducted a mailed survey of women treated for non-metastatic breast cancer in 2009-2011, 6-24 months post-treatment (N = 203). Survivors were asked about 14 potential barriers to follow-up care. We used logistic regression to explore associations between barriers and race, adjusting for covariates.
Our participants included 31 African American and 160 White survivors. At least one barrier to follow-up care was reported by 62 %. Compared to White survivors, African Americans were more likely to identify barriers related to out-of-pocket costs (28 vs. 51.6 %, p = 0.01), other health care costs (21.3 vs. 45.2 %, p = 0.01), anxiety/worry (29.4 vs. 51.6 %, p = 0.02), and transportation (4.4 vs. 16.1 %, p = 0.03). After adjustment for covariates, African Americans were three times as likely to report at least one barrier to care (odds ratio (OR) = 3.3, 95 % confidence interval (CI) = 1.1-10.1).
Barriers to care are common among breast cancer survivors, especially African American women. Financial barriers to care may prevent minority and underserved survivors from accessing follow-up care. Enhancing insurance coverage or addressing out-of-pocket costs may help address financial barriers to follow-up care among breast cancer survivors. Psychosocial care aimed at reducing fear of recurrence may also be important to improve access among African American breast cancer survivors.
C1 [Palmer, Nynikka R. A.] Univ Calif San Francisco, San Francisco Gen Hosp, Div Gen Internal Med, San Francisco, CA 94143 USA.
[Weaver, Kathryn E.] Wake Forest Sch Med, Div Publ Hlth Sci, Social Sci & Hlth Policy, Winston Salem, NC USA.
[Hauser, Sally P.; Lawrence, Julia A.] Wake Forest Comprehens Canc Ctr, Gen Surg, Winston Salem, NC USA.
[Talton, Jennifer; Case, L. Douglas] Wake Forest Sch Med, Div Publ Hlth Sci, Biostat Sci, Winston Salem, NC USA.
[Geiger, Ann M.] NCI, Hlth Serv & Econ Branch, Appl Res Program, Div Canc Control & Populat Sci, Rockville, MD USA.
RP Palmer, NRA (reprint author), Univ Calif San Francisco, San Francisco Gen Hosp, Div Gen Internal Med, San Francisco, CA 94143 USA.
EM palmern@medsfgh.ucsf.edu
OI Palmer, Nynikka/0000-0002-5311-447X
FU National Cancer Institute at the National Institutes of Health
[5R21CA155932-02, R25CA122061]
FX This work was supported by the National Cancer Institute at the National
Institutes of Health, grant numbers 5R21CA155932-02 (AM Geiger, PI) and
R25CA122061 (NE Avis, PI). We thank Kim Derzen for her contribution to
this study.
NR 42
TC 6
Z9 6
U1 2
U2 3
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0941-4355
EI 1433-7339
J9 SUPPORT CARE CANCER
JI Support. Care Cancer
PD NOV
PY 2015
VL 23
IS 11
BP 3201
EP 3209
DI 10.1007/s00520-015-2706-9
PG 9
WC Oncology; Health Care Sciences & Services; Rehabilitation
SC Oncology; Health Care Sciences & Services; Rehabilitation
GA CS1PC
UT WOS:000361838000010
PM 25821145
ER
PT J
AU Blood, JD
Wu, J
Chaplin, TM
Hommer, R
Vazquez, L
Rutherford, HJV
Mayes, LC
Crowley, MJ
AF Blood, Julia D.
Wu, Jia
Chaplin, Tara M.
Hommer, Rebecca
Vazquez, Lauren
Rutherford, Helena J. V.
Mayes, Linda C.
Crowley, Michael J.
TI The variable heart: High frequency and very low frequency correlates of
depressive symptoms in children and adolescents
SO JOURNAL OF AFFECTIVE DISORDERS
LA English
DT Article
DE Adolescence; depression; heart rate variability; time-frequency analysis
ID CARDIAC VAGAL TONE; RATE-VARIABILITY; MAJOR DEPRESSION; NEUROVISCERAL
INTEGRATION; AUTONOMIC FUNCTION; ANXIETY DISORDERS; STRESS-RESPONSE;
MODEL; ASSOCIATION; MECHANISMS
AB Background: Work examining the link between lower heart rate variability (HRV) and depression in children and adolescents is lacking, especially in light of the physiological changes that occur during pubertal development.
Method: We investigated the association between spectral measures of resting HRV and depressive symptoms among 127 children and adolescents, ages 10-17. Using spectral analysis, we evaluated (1) the association between relative high frequency (HF) HRV and depressive symptoms; (2) the predictive power of relative HF HRV for depressive symptoms in the context of relative low frequency (LF) and relative very low frequency (VLF) HRV; and (3) the relationship between relative HF, LF, and VLF band activity, age and pubertal maturation.
Results: Consistent with previous work, results revealed that relative HF HRV was negatively associated with self-reported depressive symptoms. As well, relative VLF HRV was positively associated with depressive symptoms. Regression analyses revealed that relative HF HRV and relative VLF HRV significantly predicted self-report depressive symptoms while controlling for age, sex and pubertal maturation, with relative VLF HRV emerging as the strongest indicator of depressive symptoms. Developmental findings also emerged. Age and pubertal maturation were negatively associated with relative HF HRV and positively correlated with relative VLF HRV.
Conclusions: Results provide support for the relationship between HRV and depression and suggest that both HF and VLF HRV are relevant to depression symptom severity. Findings also reinforce the importance of considering pubertal development when investigating HRV-depression associations in children and adolescents.
Limitations: Influences on cardiac control including physical activity levels and exercise patterns could be controlled in future work. Our data speak to a depressive symptom dimension and relative spectral power HRV. Thus, we cannot make strong claims about relative spectral power HRV and clinical depression. (C) 2015 Elsevier B.V. All rights reserved.
C1 [Blood, Julia D.] Univ Texas Hlth Sci Ctr San Antonio, Sch Med, San Antonio, TX 78229 USA.
[Wu, Jia; Vazquez, Lauren; Rutherford, Helena J. V.; Mayes, Linda C.; Crowley, Michael J.] Yale Univ, Sch Med, Yale Child Study Ctr, New Haven, CT USA.
[Chaplin, Tara M.] George Mason Univ, Dept Psychol, Fairfax, VA 22030 USA.
[Hommer, Rebecca] NIMH, Emot & Dev Branch, NIH, Bethesda, MD 20892 USA.
[Crowley, Michael J.] Yale Univ, Sch Med, Yale Child Study Ctr, Program Anxiety Disorders, New Haven, CT USA.
[Wu, Jia; Rutherford, Helena J. V.; Mayes, Linda C.; Crowley, Michael J.] Yale Univ, Sch Med, Yale Child Study Ctr, Dev Electrophysiol Lab, New Haven, CT USA.
[Crowley, Michael J.] Yale Univ, Sch Med, Yale Child Study Ctr, Ctr Translat Dev Neurosci, New Haven, CT USA.
RP Crowley, MJ (reprint author), Yale Child Study Ctr, 230 South Frontage Rd, New Haven, CT 06520 USA.
EM michael.crowley@yale.edu
FU NARSAD Young Investigator Award; Yale Interdisciplinary Research
Consortium on Stress, Self-Control and Addiction Pilot project funding
[1UL1RR024925-01]; NIDA [K01 DA034125, RO1-DA-06025, DA-017863, KO5];
Gustavus and Louise Pfeiffer Research Foundation; CTSA Grant from the
National Center for Research Resources (NCRR), a component of the
National Institutes of Health (NIH) [UL1 RR024139]; NIH Roadmap for
Medical Research
FX This research was supported by NARSAD Young Investigator Award (MJC),
Yale Interdisciplinary Research Consortium on Stress, Self-Control and
Addiction Pilot project funding (MJC) through 1UL1RR024925-01 (R.
Sinha); NIDA grants K01 DA034125 (MJC), RO1-DA-06025 (LCM), DA-017863
(LCM) and KO5 (LCM), and a grant from the Gustavus and Louise Pfeiffer
Research Foundation (LCM). This publication was also made possible by
CTSA Grant Number UL1 RR024139 from the National Center for Research
Resources (NCRR), a component of the National Institutes of Health
(NIH), and NIH Roadmap for Medical Research. Its contents are solely the
responsibility of the authors and do not necessarily represent the
official view of NCRR or NIH.
NR 73
TC 5
Z9 5
U1 3
U2 24
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0165-0327
EI 1573-2517
J9 J AFFECT DISORDERS
JI J. Affect. Disord.
PD NOV 1
PY 2015
VL 186
BP 119
EP 126
DI 10.1016/j.jad.2015.06.057
PG 8
WC Clinical Neurology; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA CQ9WR
UT WOS:000360966400018
PM 26233322
ER
PT J
AU Durham, B
Diamond, E
Yao, Z
Ma, J
Choi, J
Kim, E
Lee, S
Gao, YJ
Micol, JB
Campbell, P
Walsh, M
Nakitandwe, J
Estrada-Veras, J
Lacouture, M
Chung, YR
Rampal, R
Pichardo, J
Briggs, S
Hyman, D
Baselga
Janku, F
Taylor, B
Park, C
Emile, JF
Haroche, J
Rosen, N
Gruber, T
Abdel-Wahab, O
AF Durham, Benjamin
Diamond, Eli
Yao, Zhan
Ma, Jing
Choi, John
Kim, Eunhee
Lee, Stanley
Gao, Yijun
Micol, Jean-Baptiste
Campbell, Patrick
Walsh, Michael
Nakitandwe, Joy
Estrada-Veras, Juvianee
Lacouture, Mario
Chung, Young Rock
Rampal, Raajit
Pichardo, Janine
Briggs, Samuel
Hyman, David
Baselga
Janku, Filip
Taylor, Barry
Park, Christopher
Emile, Jean-Francois
Haroche, Julien
Rosen, Neal
Gruber, Tanja
Abdel-Wahab, Omar
TI DIVERSE KINASE MUTATIONS AND FUSIONS DRIVE NON-LANGERHANS CELL
HISTIOCYTOSES
SO PEDIATRIC BLOOD & CANCER
LA English
DT Meeting Abstract
C1 [Durham, Benjamin; Pichardo, Janine; Park, Christopher] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA.
[Diamond, Eli; Briggs, Samuel] Mem Sloan Kettering Canc Ctr, Dept Neurol, New York, NY 10021 USA.
[Yao, Zhan; Gao, Yijun; Rosen, Neal] Mem Sloan Kettering Canc Ctr, Mol Pharmacol & Chem Program, New York, NY 10021 USA.
[Ma, Jing; Choi, John; Nakitandwe, Joy; Gruber, Tanja] St Jude Childrens Res Hosp, Dept Pathol, Memphis, TN 38105 USA.
[Kim, Eunhee; Lee, Stanley; Micol, Jean-Baptiste; Chung, Young Rock; Taylor, Barry; Park, Christopher; Abdel-Wahab, Omar] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York, NY 10021 USA.
[Campbell, Patrick; Walsh, Michael; Gruber, Tanja] St Jude Childrens Res Hosp, Dept Oncol, Memphis, TN 38105 USA.
[Estrada-Veras, Juvianee] NHGRI, NIH, Bethesda, MD 20892 USA.
[Lacouture, Mario] Mem Sloan Kettering Canc Ctr, Dept Med, Serv Dermatol, New York, NY 10021 USA.
[Rampal, Raajit; Abdel-Wahab, Omar] Mem Sloan Kettering Canc Ctr, Dept Med, Leukemia Serv, New York, NY 10021 USA.
[Hyman, David; Baselga] Mem Sloan Kettering Canc Ctr, Dept Med, Dev Therapeut, New York, NY 10021 USA.
[Janku, Filip] Univ Texas Houston, MD Anderson Canc Ctr, Dept Med, Houston, TX 77030 USA.
[Emile, Jean-Francois] Hop Univ Ambroise Pare, Pathol Serv, Paris, France.
[Haroche, Julien] Hop La Pitie Salpetriere, Internal Med Serv, Paris, France.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1545-5009
EI 1545-5017
J9 PEDIATR BLOOD CANCER
JI Pediatr. Blood Cancer
PD NOV
PY 2015
VL 62
SU 3
BP S125
EP S126
PG 2
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA CR3JW
UT WOS:000361229700021
ER
PT J
AU Estrada-Veras, J
O'Brien, K
Gahl, W
AF Estrada-Veras, Juvianee
O'Brien, Kevin
Gahl, William
TI WHEN TWO CONDITIONS WITH SIMILAR FEATURES MEET: A CASE OF ERDHEIM
CHESTER DISEASE IN A PATIENT WITH A COMMON GENETIC DISORDER
SO PEDIATRIC BLOOD & CANCER
LA English
DT Meeting Abstract
C1 [Estrada-Veras, Juvianee; O'Brien, Kevin; Gahl, William] NHGRI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1545-5009
EI 1545-5017
J9 PEDIATR BLOOD CANCER
JI Pediatr. Blood Cancer
PD NOV
PY 2015
VL 62
SU 3
BP S127
EP S127
PG 1
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA CR3JW
UT WOS:000361229700026
ER
PT J
AU Estrada-Veras, J
O'Brien, K
Toro, C
Gahl, W
AF Estrada-Veras, Juvianee
O'Brien, Kevin
Toro, Camilo
Gahl, William
TI CEREBELLAR SYNDROME AND COGNITIVE DEFICITS IN ERDHEIM CHESTER DISEASE:
JUST ACCUMULATION OF HISTIOCYTES OR SECONDARY METABOLIC/ENDOCRINE
DEFICIT?
SO PEDIATRIC BLOOD & CANCER
LA English
DT Meeting Abstract
C1 [Estrada-Veras, Juvianee; O'Brien, Kevin; Toro, Camilo; Gahl, William] NHGRI, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1545-5009
EI 1545-5017
J9 PEDIATR BLOOD CANCER
JI Pediatr. Blood Cancer
PD NOV
PY 2015
VL 62
SU 3
BP S126
EP S126
PG 1
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA CR3JW
UT WOS:000361229700024
ER
PT J
AU Estrada-Veras, JI
Gardner, PJ
AF Estrada-Veras, Juvianee I.
Gardner, Pamela J.
TI ORAL MANIFESTATIONS OF ERDHEIM CHESTER DISEASE
SO PEDIATRIC BLOOD & CANCER
LA English
DT Meeting Abstract
C1 [Estrada-Veras, Juvianee I.] NHGRI, NIH, Med Genet Branch, Sect Human Biochem Genet, Bethesda, MD 20892 USA.
[Gardner, Pamela J.] Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1545-5009
EI 1545-5017
J9 PEDIATR BLOOD CANCER
JI Pediatr. Blood Cancer
PD NOV
PY 2015
VL 62
SU 3
BP S126
EP S126
PG 1
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA CR3JW
UT WOS:000361229700025
ER
PT J
AU Nichols, KE
Ruffo, E
Malacarne, V
Larsen, S
Das, R
Patrussi, L
Wulfing, C
Biskup, C
Schwartzberg, P
Baldari, C
Rubio, I
Snow, A
Baldanzi, G
Graziani, A
AF Nichols, Kim E.
Ruffo, Elisa
Malacarne, Valeria
Larsen, Sasha
Das, Rupali
Patrussi, Laura
Wuelfing, Christoph
Biskup, Christoph
Schwartzberg, Pamela
Baldari, Cosima
Rubio, Ignacio
Snow, Andrew
Baldanzi, Gianluca
Graziani, Andrea
TI INHIBITION OF DIACYLGLYCEROL KINASE ALPHA RESTORES SENSITIVITY TO
TCR-INDUCED CELL DEATH AND LESSENS IMMUNOPATHOLOGY IN A MURINE MODEL OF
XLP-ASSOCIATED HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS
SO PEDIATRIC BLOOD & CANCER
LA English
DT Meeting Abstract
C1 [Nichols, Kim E.] St Jude Childrens Res Hosp, Memphis, TN 38105 USA.
[Ruffo, Elisa; Malacarne, Valeria; Baldanzi, Gianluca; Graziani, Andrea] Univ Piemonte Orientale, Dept Translat Med, Novara, Italy.
[Ruffo, Elisa; Malacarne, Valeria; Baldanzi, Gianluca; Graziani, Andrea] Univ Piemonte Orientale, Inst Res & Cure Autoimmune Dis, Novara, Italy.
[Ruffo, Elisa; Malacarne, Valeria; Graziani, Andrea] Univ Vita & Salute San Raffaele, Sch Med, Milan, Italy.
[Larsen, Sasha; Snow, Andrew] Uniformed Serv Univ Hlth Sci, Dept Pharmacol, Bethesda, MD USA.
[Das, Rupali] Childrens Hosp Philadelphia, Div Oncol, Philadelphia, PA 19104 USA.
[Patrussi, Laura; Baldari, Cosima] Univ Siena, Dept Life Sci, I-53100 Siena, Italy.
[Wuelfing, Christoph] Univ Bristol, Sch Cellular & Mol Med, Bristol, Avon, England.
[Biskup, Christoph] Jena Univ Hosp, Biomol Photon Grp, Jena, Germany.
[Schwartzberg, Pamela] NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA.
[Rubio, Ignacio] Univ Jena, Ctr Sepsis Control & Care, Integrated Res & Treatment Ctr, Jena, Germany.
[Rubio, Ignacio] Univ Jena, Ctr Mol Biomed, Inst Mol Cell Biol, Jena, Germany.
NR 0
TC 0
Z9 0
U1 2
U2 2
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 NOV
PY 2015
VL 62
SU 3
BP S134
EP S134
PG 1
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA CR3JW
UT WOS:000361229700056
ER
PT J
AU Guselnikov, SV
Grayfer, L
Andino, FD
Rogozin, IB
Robert, J
Taranin, AV
AF Guselnikov, S. V.
Grayfer, L.
Andino, F. De Jesus
Rogozin, I. B.
Robert, J.
Taranin, A. V.
TI Retention of duplicated ITAM-containing transmembrane signaling subunits
in the tetraploid amphibian species Xenopus laevis
SO DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY
LA English
DT Article
DE Xenopus; Genome mining; Activating receptor complexes; TCR;
Tetraploidization; Protein dosage effect; Immunogenetics
ID LEUKOCYTE RECEPTOR COMPLEX; T-CELL DEVELOPMENT; ANTIGEN-RECEPTOR; GENE
DUPLICATION; FCR-GAMMA; IMMUNE-SYSTEM; EVOLUTION; FAMILY; TROPICALIS;
ALPHA
AB The ITAM-bearing transmembrane signaling subunits (TSS) are indispensable components of activating leukocyte receptor complexes. The TSS-encoding genes map to paralogous chromosomal regions, which are thought to arise from ancient genome tetraploidization(s). To assess a possible role of tetraploidization in the TSS evolution, we studied TSS and other functionally linked genes in the amphibian species Xenopus laevis whose genome was duplicated about 40 MYR ago. We found that X. laevis has retained a duplicated set of sixteen TSS genes, all except one being transcribed. Furthermore, duplicated TCR alpha loci and genes encoding TSS-coupling protein kinases have also been retained. No clear evidence for functional divergence of the TSS paralogs was obtained from gene expression and sequence analyses. We suggest that the main factor of maintenance of duplicated TSS genes in X. laevis was a protein dosage effect and that this effect might have facilitated the TSS set expansion in early vertebrates. Published by Elsevier Ltd.
C1 [Guselnikov, S. V.; Taranin, A. V.] Russian Acad Sci, Siberian Branch, Inst Mol & Cellular Biol, Novosibirsk 630090, Russia.
[Guselnikov, S. V.; Taranin, A. V.] Novosibirsk State Univ, Novosibirsk 630090, Russia.
[Grayfer, L.; Andino, F. De Jesus; Robert, J.] Univ Rochester, Med Ctr, MRBX, Rochester, NY 14642 USA.
[Rogozin, I. B.] NIH, Natl Ctr Biotechnol Informat NLM, Bethesda, MD 20892 USA.
RP Taranin, AV (reprint author), IMCB SB RAS, 8-2 Lavrentiev Ave, Novosibirsk 630090, Russia.
EM sguselnikov@mcb.nsc.ru; Leon_Grayfer@urmc.rochester.edu;
f_dejesus7@yahoo.com; rogozin@ncbi.nlm.nih.gov;
Jacques_Robert@urmc.rochester.edu; taranin@mcb.nsc.ru
RI Guselnikov, Sergey/N-2525-2015; Taranin, Alexander/N-5136-2015
OI Taranin, Alexander/0000-0002-9184-4238
FU Intramural Research Program of the National Library of Medicine at
National Institutes of Health (US Department Health and Human Services);
National Institutes of Health [R24-AI-059830]; National Sciences
Foundation [IOB-074271]; Howard Hughes Medical Institute; Russian Basic
Research Fund [11-04-01165-a]; Russian Academy of Sciences program
"Molecular and Cellular Biology" [6.23]
FX IBR was supported by the Intramural Research Program of the National
Library of Medicine at National Institutes of Health (US Department
Health and Human Services).; JR and FDA were supported by grants from
the National Institutes of Health (R24-AI-059830) and National Sciences
Foundation (IOB-074271).; LG was supported by a LSRF PDF from the Howard
Hughes Medical Institute.; AVT was supported by the Russian Basic
Research Fund program 11-04-01165-a and by the Russian Academy of
Sciences program "Molecular and Cellular Biology", grant number 6.23.
NR 57
TC 0
Z9 0
U1 2
U2 6
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0145-305X
EI 1879-0089
J9 DEV COMP IMMUNOL
JI Dev. Comp. Immunol.
PD NOV
PY 2015
VL 53
IS 1
BP 158
EP 168
DI 10.1016/j.dci.2015.07.002
PG 11
WC Immunology; Zoology
SC Immunology; Zoology
GA CQ7HF
UT WOS:000360772900018
PM 26170006
ER
PT J
AU Holmes, A
AF Holmes, Andrew
TI Neural mechanisms of glucocorticoid effects on the extinction of
traumatic memories
SO PSYCHONEUROENDOCRINOLOGY
LA English
DT Meeting Abstract
CT 45th Annual Meeting of the
International-Society-of-Psychoneuroendocrinology (ISPNE) on Stress and
the Brain - From Fertility to Senility
CY SEP 08-11, 2015
CL Edinburgh, SCOTLAND
SP Int Soc Psychoneuroendocrinol
C1 [Holmes, Andrew] NIAAA, NIH, Rockville, MD 20852 USA.
NR 0
TC 0
Z9 0
U1 0
U2 3
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0306-4530
J9 PSYCHONEUROENDOCRINO
JI Psychoneuroendocrinology
PD NOV
PY 2015
VL 61
MA PS4.3.3
BP 20
EP 20
DI 10.1016/j.psyneuen.2015.07.443
PG 1
WC Endocrinology & Metabolism; Neurosciences; Psychiatry
SC Endocrinology & Metabolism; Neurosciences & Neurology; Psychiatry
GA CP9XY
UT WOS:000360250400059
PM 26383331
ER
PT J
AU Meyer, J
Grant, K
Burbacher, T
Worlein, J
Kenney, C
Dettmer, A
Suomi, S
Hamell, A
Rosenberg, K
Novak, M
AF Meyer, Jerrold
Grant, Kimberly
Burbacher, Tom
Worlein, Julie
Kenney, Caroline
Dettmer, Amanda
Suomi, Stephen
Hamell, Amanda
Rosenberg, Kendra
Novak, Melinda
TI Relationship between prenatal cortisol exposure and behavioral
development in macaque monkeys
SO PSYCHONEUROENDOCRINOLOGY
LA English
DT Meeting Abstract
CT 45th Annual Meeting of the
International-Society-of-Psychoneuroendocrinology (ISPNE) on Stress and
the Brain - From Fertility to Senility
CY SEP 08-11, 2015
CL Edinburgh, SCOTLAND
SP Int Soc Psychoneuroendocrinol
C1 [Meyer, Jerrold; Hamell, Amanda; Rosenberg, Kendra; Novak, Melinda] Univ Massachusetts, Amherst, MA 01003 USA.
[Grant, Kimberly; Burbacher, Tom; Worlein, Julie; Kenney, Caroline] Washington Natl Primate Res Ctr, Seattle, WA USA.
[Hamell, Amanda; Rosenberg, Kendra] NIH, Comparat Ethol Lab, Poolesville, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 6
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0306-4530
J9 PSYCHONEUROENDOCRINO
JI Psychoneuroendocrinology
PD NOV
PY 2015
VL 61
MA PO25
BP 30
EP 31
DI 10.1016/j.psyneuen.2015.07.473
PG 2
WC Endocrinology & Metabolism; Neurosciences; Psychiatry
SC Endocrinology & Metabolism; Neurosciences & Neurology; Psychiatry
GA CP9XY
UT WOS:000360250400089
PM 26383357
ER
PT J
AU Hardy, T
McCarthy, D
Fourie, N
Henderson, W
AF Hardy, Theresa
McCarthy, Donnalee
Fourie, Nicolaas
Henderson, Wendy
TI The relationship of anti-Mullerian hormone levels and urine cortisol in
women with chronic abdominal pain
SO PSYCHONEUROENDOCRINOLOGY
LA English
DT Meeting Abstract
CT 45th Annual Meeting of the
International-Society-of-Psychoneuroendocrinology (ISPNE) on Stress and
the Brain - From Fertility to Senility
CY SEP 08-11, 2015
CL Edinburgh, SCOTLAND
SP Int Soc Psychoneuroendocrinol
C1 [Hardy, Theresa; McCarthy, Donnalee] Marquette Univ, Milwaukee, WI 53233 USA.
[Hardy, Theresa; Fourie, Nicolaas; Henderson, Wendy] NIH, Bethesda, MD 20892 USA.
OI Henderson, Wendy/0000-0003-3924-7118
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 0306-4530
J9 PSYCHONEUROENDOCRINO
JI Psychoneuroendocrinology
PD NOV
PY 2015
VL 61
MA PO136
BP 70
EP 70
DI 10.1016/j.psyneuen.2015.07.584
PG 1
WC Endocrinology & Metabolism; Neurosciences; Psychiatry
SC Endocrinology & Metabolism; Neurosciences & Neurology; Psychiatry
GA CP9XY
UT WOS:000360250400200
PM 26383470
ER
PT J
AU Mondul, AM
Moore, SC
Weinstein, SJ
Karoly, ED
Sampson, JN
Albanes, D
AF Mondul, Alison M.
Moore, Steven C.
Weinstein, Stephanie J.
Karoly, Edward D.
Sampson, Joshua N.
Albanes, Demetrius
TI Metabolomic analysis of prostate cancer risk in a prospective cohort:
The alpha-tocolpherol, beta-carotene cancer prevention (ATBC) study
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE metabolomics; prostate cancer; serology; energy metabolism; lipid
metabolism; biomarkers; thyroxine; TMAO; TCA cycle; Warburg
ID INTERMEDIARY METABOLISM; LIPID-METABOLISM; STATIN USE; CELLS;
REQUIREMENTS; EPIDEMIOLOGY; METAANALYSIS; OXIDATION; PATHWAYS; SYSTEMS
AB Despite decades of concerted epidemiological research, relatively little is known about the etiology of prostate cancer. As genome-wide association studies have identified numerous genetic variants, so metabolomic profiling of blood and other tissues represents an agnostic, broad-spectrum approach for examining potential metabolic biomarkers of prostate cancer risk. To this end, we conducted a prospective analysis of prostate cancer within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study cohort based on 200 cases (100 aggressive) and 200 controls (age- and blood collection date-matched) with fasting serum collected up to 20 years prior to case diagnoses. Ultrahigh performance liquid chromatography/mass spectroscopy and gas chromatography/mass spectroscopy identified 626 compounds detected in >95% of the men and the odds ratio per 1-standard deviation increase in log-metabolite levels and risk were estimated using conditional logistic regression. We observed strong inverse associations between energy and lipid metabolites and aggressive cancer (p=0.018 and p=0.041, respectively, for chemical class over-representation). Inositol-1-phosphate showed the strongest association (OR=0.56, 95% CI=0.39-0.81, p=0.002) and glycerophospholipids and fatty acids were heavily represented; e.g., oleoyl-linoleoyl-glycerophosphoinositol (OR=0.64, p=0.004), 1-stearoylglycerophosphoglycerol (OR=0.65, p=0.025), stearate (OR=0.65, p=0.010) and docosadienoate (OR=0.66, p=0.014). Both alpha-ketoglutarate and citrate were associated with aggressive disease risk (OR=0.69, 95% CI=0.51-0.94, p=0.02; OR=0.69, 95% CI=0.50-0.95, p=0.02), as were elevated thyroxine and trimethylamine oxide (OR=1.65, 95% CI=1.08-2.54, p=0.021; and OR=1.36, 95% CI=1.02-1.81, p=0.039). Serum PSA adjustment did not alter the findings. Our data reveal several metabolomic leads that may have pathophysiological relevance to prostate carcinogenesis and should be examined through additional research.
What's new?
Prostate cancer is the second most common cancer in men, yet few modifiable risk factors are known. A window to the study of modifiable risk factors is the metabolome, with prospective metabolomic serum profiling being a promising new investigative approach. In prostate cancer, use of this approach had resulted in the identification of numerous circulating lipids associated with risk of aggressive disease. Here, the authors report inverse associations between aggressive disease and energy and lipid metabolites, including alpha-ketoglutarate, citrate, inositol-1-phosphate and several glycerophospholipids and fatty acids. Some of the metabolites may be relevant to prostate cancer development and progression.
C1 [Mondul, Alison M.] Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA.
[Moore, Steven C.; Weinstein, Stephanie J.; Sampson, Joshua N.; Albanes, Demetrius] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA.
[Karoly, Edward D.] Metabolon, Morrisville, NC USA.
RP Albanes, D (reprint author), NCI, Div Canc Epidemiol & Genet, 9609 Med Ctr Dr 6E342, Bethesda, MD 20892 USA.
EM daa@nih.gov
RI Moore, Steven/D-8760-2016;
OI Moore, Steven/0000-0002-8169-1661; Mondul, Alison/0000-0002-8843-1416
FU Intramural Research Program of the Division of Cancer Epidemiology and
Genetics; DHHS; Intramural Research Program of the Division of Cancer
Epidemiology and Genetics, National Cancer Institute, NIH, DHHS
FX Grant sponsor: Intramural Research Program of the Division of Cancer
Epidemiology and Genetics, National Cancer Institute, NIH, DHHS
NR 42
TC 15
Z9 15
U1 6
U2 48
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0020-7136
EI 1097-0215
J9 INT J CANCER
JI Int. J. Cancer
PD NOV 1
PY 2015
VL 137
IS 9
BP 2124
EP 2132
DI 10.1002/ijc.29576
PG 9
WC Oncology
SC Oncology
GA CP3ME
UT WOS:000359782700010
PM 25904191
ER
PT J
AU Campa, D
Rizzato, C
Stolzenberg-Solomon, R
Pacetti, P
Vodicka, P
Cleary, SP
Capurso, G
Bueno-de-Mesquita, HB
Werner, J
Gazouli, M
Butterbach, K
Ivanauskas, A
Giese, N
Petersen, GM
Fogar, P
Wang, ZM
Bassi, C
Ryska, M
Theodoropoulos, GE
Kooperberg, C
Li, DH
Greenhalf, W
Pasquali, C
Hackert, T
Fuchs, CS
Mohelnikova-Duchonova, B
Sperti, C
Funel, N
Dieffenbach, AK
Wareham, NJ
Buring, J
Holcatova, I
Costello, E
Zambon, CF
Kupcinskas, J
Risch, HA
Kraft, P
Bracci, PM
Pezzilli, R
Olson, SH
Sesso, HD
Hartge, P
Strobel, O
Malecka-Panas, E
Visvanathan, K
Arslan, AA
Pedrazzoli, S
Soucek, P
Gioffreda, D
Key, TJ
Talar-Wojnarowska, R
Scarpa, A
Mambrini, A
Jacobs, EJ
Jamroziak, K
Klein, A
Tavano, F
Bambi, F
Landi, S
Austin, MA
Vodickova, L
Brenner, H
Chanock, SJ
Delle Fave, G
Piepoli, A
Cantore, M
Zheng, W
Wolpin, BM
Amundadottir, LT
Canzian, F
AF Campa, Daniele
Rizzato, Cosmeri
Stolzenberg-Solomon, Rachael
Pacetti, Paola
Vodicka, Pavel
Cleary, Sean P.
Capurso, Gabriele
Bueno-de-Mesquita, H. B(as)
Werner, Jens
Gazouli, Maria
Butterbach, Katja
Ivanauskas, Audrius
Giese, Nathalia
Petersen, Gloria M.
Fogar, Paola
Wang, Zhaoming
Bassi, Claudio
Ryska, Miroslav
Theodoropoulos, George E.
Kooperberg, Charles
Li, Donghui
Greenhalf, William
Pasquali, Claudio
Hackert, Thilo
Fuchs, Charles S.
Mohelnikova-Duchonova, Beatrice
Sperti, Cosimo
Funel, Niccola
Dieffenbach, Aida Karina
Wareham, Nicholas J.
Buring, Julie
Holcatova, Ivana
Costello, Eithne
Zambon, Carlo-Federico
Kupcinskas, Juozas
Risch, Harvey A.
Kraft, Peter
Bracci, Paige M.
Pezzilli, Raffaele
Olson, Sara H.
Sesso, Howard D.
Hartge, Patricia
Strobel, Oliver
Malecka-Panas, Ewa
Visvanathan, Kala
Arslan, Alan A.
Pedrazzoli, Sergio
Soucek, Pavel
Gioffreda, Domenica
Key, Timothy J.
Talar-Wojnarowska, Renata
Scarpa, Aldo
Mambrini, Andrea
Jacobs, Eric J.
Jamroziak, Krzysztof
Klein, Alison
Tavano, Francesca
Bambi, Franco
Landi, Stefano
Austin, Melissa A.
Vodickova, Ludmila
Brenner, Hermann
Chanock, Stephen J.
Delle Fave, Gianfranco
Piepoli, Ada
Cantore, Maurizio
Zheng, Wei
Wolpin, Brian M.
Amundadottir, Laufey T.
Canzian, Federico
TI TERT gene harbors multiple variants associated with pancreatic cancer
susceptibility
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE pancreatic cancer; polymorphisms; telomerase; susceptibility
ID GENOME-WIDE ASSOCIATION; TELOMERE LENGTH; RISK; LOCI; 5P15.33;
POLYMORPHISMS; METAANALYSIS; POPULATION; DISEASE; IDENTIFICATION
AB A small number of common susceptibility loci have been identified for pancreatic cancer, one of which is marked by rs401681 in the TERT-CLPTM1L gene region on chromosome 5p15.33. Because this region is characterized by low linkage disequilibrium, we sought to identify whether additional single nucleotide polymorphisms (SNPs) could be related to pancreatic cancer risk, independently of rs401681. We performed an in-depth analysis of genetic variability of the telomerase reverse transcriptase (TERT) and the telomerase RNA component (TERC) genes, in 5,550 subjects with pancreatic cancer and 7,585 controls from the PANcreatic Disease ReseArch (PANDoRA) and the PanScan consortia. We identified a significant association between a variant in TERT and pancreatic cancer risk (rs2853677, odds ratio = 0.85; 95% confidence interval = 0.80-0.90, p = 8.3 x 10(-8)). Additional analysis adjusting rs2853677 for rs401681 indicated that the two SNPs are independently associated with pancreatic cancer risk, as suggested by the low linkage disequilibrium between them (r(2) = 0.07, D = 0.28). Three additional SNPs in TERT reached statistical significance after correction for multiple testing: rs2736100 (p = 3.0 x 10(-5)), rs4583925 (p = 4.0 x 10(-5)) and rs2735948 (p = 5.0 x 10(-5)). In conclusion, we confirmed that the TERT locus is associated with pancreatic cancer risk, possibly through several independent variants.
What's new?
Most pancreatic cancer patients do not survive long after diagnosis, and, so far, there are not many genetic markers to help screen for the disease. In search of genetic predictors of pancreatic cancer, the authors zoomed in on a region linked to susceptibility to the disease. They measured the frequency of different variants of two genes, telomerase reverse transcriptase and telomerase RNA component, among thousands of pancreatic cancer patients and controls. They identified several variants of the TERT gene that indicate a boosted pancreatic cancer risk, and which may develop into useful prognostic tools.
C1 [Campa, Daniele] German Canc Res Ctr, Div Canc Epidemiol, D-69120 Heidelberg, Germany.
[Rizzato, Cosmeri; Canzian, Federico] German Canc Res Ctr, Genom Epidemiol Grp, D-69120 Heidelberg, Germany.
[Stolzenberg-Solomon, Rachael; Wang, Zhaoming; Hartge, Patricia; Chanock, Stephen J.; Amundadottir, Laufey T.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Pacetti, Paola; Mambrini, Andrea; Cantore, Maurizio] ASL1 Massa Carrara, Dept Oncol, Massa Carrara, Italy.
[Vodicka, Pavel; Vodickova, Ludmila] Acad Sci Czech Republic, Inst Expt Med, Dept Mol Biol Canc, Prague, Czech Republic.
[Cleary, Sean P.] Univ Toronto, Dept Surg, Univ Hlth Network, Toronto, ON, Canada.
[Capurso, Gabriele; Delle Fave, Gianfranco] Univ Roma La Sapienza, S Andrea Hosp, Digest & Liver Dis Unit, I-00185 Rome, Italy.
[Bueno-de-Mesquita, H. B(as)] Natl Inst Publ Hlth & Environm RIVM, Dept Determinants Chron Dis DCD, Bilthoven, Netherlands.
[Bueno-de-Mesquita, H. B(as)] Univ Med Ctr, Dept Gastroenterol & Hepatol, Utrecht, Netherlands.
[Bueno-de-Mesquita, H. B(as)] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England.
[Bueno-de-Mesquita, H. B(as)] Univ Malaya, Fac Med, Dept Social & Prevent Med, Kuala Lumpur, Malaysia.
[Werner, Jens; Giese, Nathalia; Hackert, Thilo; Strobel, Oliver] Univ Heidelberg Hosp, Dept Gen Surg, Heidelberg, Germany.
[Gazouli, Maria] Univ Athens, Sch Med, Dept Basic Med Sci, Biol Lab, GR-11527 Athens, Greece.
[Butterbach, Katja; Dieffenbach, Aida Karina; Brenner, Hermann] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, D-69120 Heidelberg, Germany.
[Ivanauskas, Audrius; Kupcinskas, Juozas] Lithuanian Univ Hlth Sci, Dept Gastroenterol, Kaunas, Lithuania.
[Petersen, Gloria M.] Mayo Clin, Coll Med, Dept Hlth Sci Res, Rochester, MN USA.
[Fogar, Paola] Univ Hosp Padua, Dept Lab Med, Padua, Italy.
[Bassi, Claudio] Univ & Hosp Trust Verona, Surg & Oncol Dept, Pancreas Inst, Verona, Italy.
[Ryska, Miroslav] Charles Univ Prague, Fac Med 2, Dept Surg, Prague, Czech Republic.
[Ryska, Miroslav] Cent Mil Hosp, Prague, Czech Republic.
[Theodoropoulos, George E.] Univ Athens, Sch Med, Dept Propaedeut Surg 1, GR-11527 Athens, Greece.
[Kooperberg, Charles] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA.
[Li, Donghui] Univ Texas MD Anderson Canc Ctr, Dept Gastrointestinal Med Oncol, Houston, TX 77030 USA.
[Greenhalf, William; Costello, Eithne] Univ Liverpool, Natl Inst Hlth Res, Liverpool Pancreas Biomed Res Unit, Liverpool L69 3BX, Merseyside, England.
[Pasquali, Claudio; Sperti, Cosimo] Univ Padua, Dept Surg Gastroenterol & Oncol DISCOG, Padua, Italy.
[Fuchs, Charles S.; Wolpin, Brian M.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
[Mohelnikova-Duchonova, Beatrice] Palacky Univ, Sch Med, Dept Oncol, CR-77147 Olomouc, Czech Republic.
[Mohelnikova-Duchonova, Beatrice] Teaching Hosp Olomouc, Olomouc, Czech Republic.
[Funel, Niccola] Univ Hosp Pisa, Dept Surg, Unit Expt Surg Pathol, Pisa, Italy.
[Dieffenbach, Aida Karina; Brenner, Hermann] German Canc Consortium DKTK, Heidelberg, Germany.
[Wareham, Nicholas J.] Univ Cambridge, MRC, Epidemiol Unit, Inst Metab Sci, Cambridge, England.
[Buring, Julie; Sesso, Howard D.] Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02115 USA.
[Buring, Julie; Sesso, Howard D.] Brigham & Womens Hosp, Dept Med, Div Aging, Boston, MA 02115 USA.
[Buring, Julie; Sesso, Howard D.] Harvard Univ, Sch Med, Boston, MA USA.
[Holcatova, Ivana] Charles Univ Prague, Fac Med 1, Inst Hyg & Epidemiol, Prague, Czech Republic.
[Zambon, Carlo-Federico] Univ Padua, Dept Med DIMED, Padua, Italy.
[Risch, Harvey A.] Yale Univ, Sch Publ Hlth, Dept Epidemiol & Publ Hlth, New Haven, CT USA.
[Kraft, Peter; Sesso, Howard D.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Bracci, Paige M.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
[Pezzilli, Raffaele] St Orsola Malpighi Hosp, Pancreas Unit, Dept Digest Dis & Internal Med, Bologna, Italy.
[Olson, Sara H.] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA.
[Malecka-Panas, Ewa; Talar-Wojnarowska, Renata] Med Univ Lodz, Dept Digest Tract Dis, Lodz, Poland.
[Visvanathan, Kala] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Arslan, Alan A.] NYU, Sch Med, Dept Obstet & Gynecol, Div Epidemiol, New York, NY USA.
[Arslan, Alan A.] NYU, Sch Med, Dept Environm Med, New York, NY USA.
[Arslan, Alan A.] NYU, Sch Med, Dept Populat Hlth, New York, NY USA.
[Pedrazzoli, Sergio] Univ Padua, Surg Clin 4, Padua, Italy.
[Soucek, Pavel] Natl Inst Publ Hlth, Dept Toxicogen, Prague, Czech Republic.
[Gioffreda, Domenica; Tavano, Francesca; Piepoli, Ada] IRCCS Sci Inst & Reg Gen Hosp Casa Sollievo Della, Div Gastroenterol, San Giovanni Rotondo, Italy.
[Gioffreda, Domenica; Tavano, Francesca; Piepoli, Ada] IRCCS Sci Inst & Reg Gen Hosp Casa Sollievo Della, Res Lab, San Giovanni Rotondo, Italy.
[Key, Timothy J.] Univ Oxford, Nuffield Dept Populat Hlth, Canc Epidemiol Unit, Oxford, England.
[Scarpa, Aldo] Univ & Hosp Trust Verona, ARC NET Ctr Appl Res Canc, Verona, Italy.
[Jacobs, Eric J.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA.
[Jamroziak, Krzysztof] Inst Hematol & Transfus Med, Dept Hematol, Warsaw, Poland.
[Klein, Alison] Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA.
[Bambi, Franco] Azienda Osped Univ Meyer, Blood Transfus Serv, Florence, Italy.
[Landi, Stefano] Univ Pisa, Dept Biol, Pisa, Italy.
[Austin, Melissa A.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Zheng, Wei] Vanderbilt Univ, Med Ctr, Dept Med, Nashville, TN USA.
[Zheng, Wei] Vanderbilt Univ, Med Ctr, Vanderbilt Ingram Canc Ctr, Nashville, TN USA.
RP Canzian, F (reprint author), German Canc Res Ctr, Genom Epidemiol Grp, Neuenheimer Feld 280, D-69120 Heidelberg, Germany.
EM f.canzian@dkfz.de
RI Zambon, Carlo Federico/J-8187-2016; Campa, Daniele/K-1617-2016; Tavano,
Francesca/K-2203-2016; Piepoli, Ada/K-9299-2016; scarpa,
aldo/K-6832-2016; Talar-Wojnarowska, Renata/T-1009-2016; Brenner,
Hermann/B-4627-2017;
OI Landi, Stefano/0000-0001-8364-6357; Zambon, Carlo
Federico/0000-0002-4244-879X; Campa, Daniele/0000-0003-3220-9944;
Tavano, Francesca/0000-0002-8831-7349; Piepoli, Ada/0000-0001-7487-8754;
scarpa, aldo/0000-0003-1678-739X; Brenner, Hermann/0000-0002-6129-1572;
Soucek, Pavel/0000-0002-4294-6799
FU Czech Science Foundation [P301/12/1734]; Internal Grant Agency of the
Czech Ministry of Health [IGA NT 13 263]; NIH [5R01 CA098870, R01
CA102765, R21 CA115878, R37 CA70867, P01 CA87969, P01 CA55075, U54
CA155626, P50 CA127003, R01 CA124908, R01 CA49449, 1UM1 CA167552, CA
97193, CA 34944, CA 40360, HL 26490, HL 34595, CA 047988, HL 043851, HL
080467]; Baden-Wurttemberg State Ministry of Research, Science and Arts;
Italian Ministry of Health [RC1203GA57, RC1303GA53, RC1303GA54,
RC1303GA50]; National Institute for Health Research Liverpool Pancreas
Biomedical Research Unit, UK
FX Grant sponsor: Czech Science Foundation; Grant number: P301/12/1734;
Grant sponsor: Internal Grant Agency of the Czech Ministry of Health;
Grant number: IGA NT 13 263 (to M.R.); Grant sponsor: NIH; Grant
numbers: 5R01 CA098870 (to H.A.R.), R01 CA102765 and R21 CA115878 (to
M.A.A.), R37 CA70867 (to the Shanghai Women's Health Study), P01
CA87969, P01 CA55075, U54 CA155626, P50 CA127003, R01 CA124908, R01
CA49449 and 1UM1 CA167552 (to the Nurses Health Study and the Health
Professionals Follow-Up Study), CA 97193, CA 34944, CA 40360, HL 26490
and HL 34595 (to the Physicians' Health Study), CA 047988, HL 043851 and
HL 080467 (to the Women's Health Study); Grant sponsor:
Baden-Wurttemberg State Ministry of Research, Science and Arts (to the
ESTHER study); Grant number: "5 x 1000" voluntary contribution; Grant
sponsor: Italian Ministry of Health; Grant numbers: RC1203GA57,
RC1303GA53, RC1303GA54 and RC1303GA50; Grant sponsor: National Institute
for Health Research Liverpool Pancreas Biomedical Research Unit, UK
NR 50
TC 8
Z9 8
U1 2
U2 34
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0020-7136
EI 1097-0215
J9 INT J CANCER
JI Int. J. Cancer
PD NOV 1
PY 2015
VL 137
IS 9
BP 2175
EP 2183
DI 10.1002/ijc.29590
PG 9
WC Oncology
SC Oncology
GA CP3ME
UT WOS:000359782700016
PM 25940397
ER
PT J
AU Linet, MS
Yin, SN
Gilbert, ES
Dores, GM
Hayes, RB
Vermeulen, R
Tian, HY
Lan, Q
Portengen, L
Ji, BT
Li, GL
Rothman, N
AF Linet, Martha S.
Yin, Song-Nian
Gilbert, Ethel S.
Dores, Graca M.
Hayes, Richard B.
Vermeulen, Roel
Tian, Hao-Yuan
Lan, Qing
Portengen, Lutzen
Ji, Bu-Tian
Li, Gui-Lan
Rothman, Nathaniel
CA Chinese Ctr Dis Control Prevention
US Natl Canc Inst
Benzene Study Grp
TI A retrospective cohort study of cause-specific mortality and incidence
of hematopoietic malignancies in Chinese benzene-exposed workers
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE benzene; leukemia; lymphoma; lung cancer; mortality
ID EPIDEMIOLOGIC RISK ASSESSMENT; ACUTE MYELOID-LEUKEMIA;
NON-HODGKIN-LYMPHOMA; MULTIPLE-MYELOMA; OCCUPATIONAL-EXPOSURE; PETROLEUM
WORKERS; CANCER-MORTALITY; APLASTIC-ANEMIA; METAANALYSIS; NEOPLASMS
AB Benzene exposure has been causally linked with acute myeloid leukemia (AML), but inconsistently associated with other hematopoietic, lymphoproliferative and related disorders (HLD) or solid tumors in humans. Many neoplasms have been described in experimental animals exposed to benzene. We used Poisson regression to estimate adjusted relative risks (RR) and the likelihood ratio statistic to derive confidence intervals for cause-specific mortality and HLD incidence in 73,789 benzene-exposed compared with 34,504 unexposed workers in a retrospective cohort study in 12 cities in China. Follow-up and outcome assessment was based on factory, medical and other records. Benzene-exposed workers experienced increased risks for all-cause mortality (RR = 1.1, 95% CI=1.1, 1.2) due to excesses of all neoplasms (RR = 1.3, 95% CI = 1.2, 1.4), respiratory diseases (RR = 1.7, 95% CI=1.2, 2.3) and diseases of blood forming organs (RR = infinity, 95% CI = 3.4, ). Lung cancer mortality was significantly elevated (RR = 1.5, 95% CI = 1.2, 1.9) with similar RRs for males and females, based on three-fold more cases than in our previous follow-up. Significantly elevated incidence of all myeloid disorders reflected excesses of myelodysplastic syndrome/acute myeloid leukemia (RR = 2.7, 95% CI = 1.2, 6.6) and chronic myeloid leukemia (RR = 2.5, 95% CI = 0.8, 11), and increases of all lymphoid disorders included excesses of non-Hodgkin lymphoma (RR = 3.9, 95% CI = 1.5, 13) and all lymphoid leukemia (RR = 5.4, 95% CI = 1.0, 99). The 28-year follow-up of Chinese benzene-exposed workers demonstrated increased risks of a broad range of myeloid and lymphoid neoplasms, lung cancer, and respiratory diseases and suggested possible associations with other malignant and non-malignant disorders.
What's new?
More than two million workers worldwide are exposed to benzene each year. In this long-term study of Chinese workers, the authors found that chronic benzene exposure was associated with a substantial increase in the risk of myeloid and lymphoid neoplasms, lung cancer, and respiratory diseases. The results also suggest possible associations with other malignant and non-malignant disorders.
C1 [Linet, Martha S.; Gilbert, Ethel S.; Dores, Graca M.] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Rockville, MD 20850 USA.
[Yin, Song-Nian; Tian, Hao-Yuan; Li, Gui-Lan] Chinese Ctr Dis Control & Prevent, Natl Inst Occupat Hlth & Poison Control, Beijing, Peoples R China.
[Hayes, Richard B.] NYU, Sch Med, Dept Populat Hlth, Div Epidemiol, New York, NY USA.
[Vermeulen, Roel] Univ Utrecht, Inst Risk Assessment Sci, Div Environm Epidemiol, Utrecht, Netherlands.
[Lan, Qing; Ji, Bu-Tian; Rothman, Nathaniel] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Rockville, MD 20850 USA.
[Portengen, Lutzen] Univ Utrecht, Inst Risk Assessment Sci, Utrecht, Netherlands.
RP Linet, MS (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, 9609 Med Ctr Dr, Rockville, MD 20850 USA.
EM linetm@mail.nih.gov
RI Vermeulen, Roel/F-8037-2011;
OI Vermeulen, Roel/0000-0003-4082-8163; Hayes, Richard/0000-0002-0918-661X
FU Intramural Research Program of the National Institutes of Health;
National Cancer Institute; US Public Health Service of the Department of
Health and Human Services
FX Grant sponsor: Intramural Research Program of the National Institutes of
Health; National Cancer Institute; US Public Health Service of the
Department of Health and Human Services
NR 59
TC 4
Z9 4
U1 2
U2 34
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0020-7136
EI 1097-0215
J9 INT J CANCER
JI Int. J. Cancer
PD NOV 1
PY 2015
VL 137
IS 9
BP 2184
EP 2197
DI 10.1002/ijc.29591
PG 14
WC Oncology
SC Oncology
GA CP3ME
UT WOS:000359782700017
PM 25944549
ER
PT J
AU Zhao, Q
Tran, H
Dimitrov, DS
Cheung, NKV
AF Zhao, Qi
Tran, Hoa
Dimitrov, Dimiter S.
Cheung, Nai-Kong V.
TI A dual-specific anti-IGF-1/IGF-2 human monoclonal antibody alone and in
combination with temsirolimus for therapy of neuroblastoma
SO INTERNATIONAL JOURNAL OF CANCER
LA English
DT Article
DE IGF-1; IGF-2; temsirolimus; chemotherapy; neuroblastoma
ID GROWTH-FACTOR-RECEPTOR; MTOR INHIBITOR TEMSIROLIMUS; BREAST-CANCER;
IN-VITRO; SIGNAL-TRANSDUCTION; PEDIATRIC-PATIENTS; INSULIN-RECEPTOR;
SOLID TUMORS; CELL-LINES; IGF SYSTEM
AB The insulin-like growth factors (IGFs), IGF-1 and IGF-2, have been implicated in the growth, survival and metastasis of a broad range of malignancies including pediatric tumors. They bind to the IGF receptor type 1 (IGF-1R) and the insulin receptor (IR) which are overexpressed in many types of solid malignancies. Activation of the IR by IGF-2 results in increased survival of tumor cells. We have previously identified a novel human monoclonal antibody, m708.5, which binds with high (pM) affinity to both human IGF-1 and IGF-2, and potently inhibits phosphorylation of the IGF-1R and the IR in tumor cells. m708.5 exhibited strong antitumor activity as a single agent against most cell lines derived from neuroblastoma, Ewing family of tumor, rhabdomyosarcoma and osteosarcoma. When tested in neuroblastoma cell lines, it showed strong synergy with temsirolimus and synergy with chemotherapeutic agents in vitro. In xenograft models, the combination of m708.5 and temsirolimus significantly inhibited neuroblastoma growth and prolonged mouse survival. Taken together, these results support the clinical development of m708.5 for pediatric solid tumors with potential for synergy with chemotherapy and mTOR inhibitors.
What's new? Insulin-like growth factors (IGF) 1 and 2 promote the biogenesis of neuroblastoma, a frequent neuroendocrine tumor in early childhood. Here the authors show that targeting IGF-1 and 2 with a specific antibody (m708.5) has anti-tumor activity in neuroblastoma cell lines as well as in cell culture models of the Ewing family of tumors, rhabdomyosarcoma, and osteosarcoma. Similarly, in xenograft mouse models of neuroblastoma, m798.5 together with an inhibitor of mammalian target of rapamycin (mTOR) suppressed tumor growth and increased survival, supporting a potential clinical application of antibodies targeting IGF-1/2 in children afflicted with solid tumors.
C1 [Zhao, Qi; Tran, Hoa; Cheung, Nai-Kong V.] Mem Sloan Kettering Canc Ctr, Dept Pediat, New York, NY 10021 USA.
[Zhao, Qi] Chinese Acad Sci, Shenzhen Inst Adv Technol, Lab Fully Human Antibody Engn, Beijing 100864, Guangdong, Peoples R China.
[Dimitrov, Dimiter S.] NCI, Prot Interact Sect, Expt Immunol Lab, Canc & Inflammat Program,Ctr Canc Res,NIH, Frederick, MD 21701 USA.
RP Cheung, NKV (reprint author), Mem Sloan Kettering Canc Ctr, Dept Pediat, 1275 York Ave, New York, NY 10021 USA.
EM cheungn@mskcc.org
FU Commonwealth Foundation for Cancer Research; Experimental Therapeutics
Center of MSK; Cookies for Kids' Cancer; Robert Steel Foundation;
Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research
FX Grant sponsors: Mr. William H. Goodwin and Mrs. Alice Goodwin and the
Commonwealth Foundation for Cancer Research and The Experimental
Therapeutics Center of MSK, Cookies for Kids' Cancer, the Robert Steel
Foundation and the Intramural Research Program of the NIH, National
Cancer Institute, Center for Cancer Research
NR 42
TC 2
Z9 2
U1 0
U2 27
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0020-7136
EI 1097-0215
J9 INT J CANCER
JI Int. J. Cancer
PD NOV 1
PY 2015
VL 137
IS 9
BP 2243
EP 2252
DI 10.1002/ijc.29588
PG 10
WC Oncology
SC Oncology
GA CP3ME
UT WOS:000359782700023
PM 25924852
ER
PT J
AU Moss, HB
Goldstein, RB
Chen, CM
Yi, HY
AF Moss, Howard B.
Goldstein, Rise B.
Chen, Chiung M.
Yi, Hsiao-Ye
TI Patterns of use of other drugs among those with alcohol dependence:
Associations with drinking behavior and psychopathology
SO ADDICTIVE BEHAVIORS
LA English
DT Article
DE Alcohol dependence; Polysubstance use; Drug use; Alcohol use;
Psychopathology
ID NATIONAL EPIDEMIOLOGIC SURVEY; GENERAL-POPULATION SAMPLE; PSYCHIATRIC
DIAGNOSTIC MODULES; INTERVIEW SCHEDULE AUDADIS; UNITED-STATES;
USE-DISORDER; REPRESENTATIVE SAMPLE; TERM OUTCOMES; POLYDRUG USE; IV
AB Introduction: Alcohol dependence (AD) presents with substantial clinical heterogeneity, induding concurrent use of non-alcohol drugs. Here, we examine specific patterns of concurrent non-alcohol substance use during the previous year among a nationally representative sample of adults with DSM-IV AD, and estimate their population prevalence in the U.S. We then evaluate alcohol use behavior and comorbid psychopathology among respondents with AD according to their patterns of concurrent non-alcohol substance use.
Methods: These analyses utilized data from Waves 1 and 2 of the National Epidemiologic Survey on Alcohol and Related Conditions. Latent class analyses classified respondents with AD into four clinically meaningful patterns of concurrent substance use: (1) use of alcohol only; (2) use of alcohol and tobacco only; (3) use of alcohol, tobacco and cannabis; and (4) use of alcohol, tobacco, cannabis, cocaine, and other illicit drug(s).
Results: Among AD respondents, the most prevalent pattern was the use of alcohol and tobacco only (weighted percentage, 32.4%), followed by the use of alcohol only (weighted percentage, 27.5%). AD respondents who used alcohol, tobacco, cannabis, cocaine, and other illicit drug(s) (weighted percentage, 253%) manifested the most severe pattern of alcohol consumption, and had significant overrepresentations of major depression, panic, and other anxiety disorders as well as paranoid, schizotypal, borderline, antisocial, and histrionic personality disorders compared with those who used alcohol alone.
Conclusions: Specific patterns of concurrent substance use convey important information regarding the clinical presentation and prognosis for AD. In particular, concurrent use of illicit drugs over the past year by AD individuals was associated with greater severity and comorbid psychopathology. These data suggest the need for pragmatic trials of AD interventions that take into account patterns of substance use behavior in addition to an AD diagnosis. Published by Elsevier Ltd.
C1 [Moss, Howard B.; Goldstein, Rise B.] NIAAA, Bethesda, MD 20892 USA.
[Chen, Chiung M.; Yi, Hsiao-Ye] CSR Inc, Alcohol Epidemiol Data Syst, Arlington, VA 22201 USA.
RP Moss, HB (reprint author), Medicat Assisted Therapy, 1150 Silverado St, La Jolla, CA 92037 USA.
OI Goldstein, Rise/0000-0002-9603-9473
FU National Institute on Alcohol Abuse and Alcoholism
FX Funding for this study was provided by National Institute on Alcohol
Abuse and Alcoholism using internal funds. At the institutional level,
NIAAA had no role in the study design, collection, analysis or
interpretation of the data, writing the manuscript, or the decision to
submit the paper for publication. However, the first author, Dr. Moss
was Associate Director of NIAAA at the time this work was conducted.
NR 47
TC 7
Z9 7
U1 1
U2 26
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0306-4603
EI 1873-6327
J9 ADDICT BEHAV
JI Addict. Behav.
PD NOV
PY 2015
VL 50
BP 192
EP 198
DI 10.1016/j.addbeh.2015.06.041
PG 7
WC Psychology, Clinical; Substance Abuse
SC Psychology; Substance Abuse
GA CO4YO
UT WOS:000359167000034
PM 26151585
ER
PT J
AU Liu, HW
Ren, W
Zhao, JY
Zhao, HF
Wu, XQ
Shi, P
Zhou, QF
Shung, KK
AF Liu, Hongwei
Ren, Wei
Zhao, Jinyan
Zhao, Huifeng
Wu, Xiaoqing
Shi, Peng
Zhou, Qifa
Shung, K. Kirk
TI Design and fabrication of high frequency BNT film based linear array
transducer
SO CERAMICS INTERNATIONAL
LA English
DT Article
DE Lead-free BNT film; Micro-machining technologies; High frequency
ultrasound array transducer
ID THICK-FILMS; ULTRASONIC TRANSDUCERS; ELECTRICAL-PROPERTIES; COMPOSITE;
ELEMENTS
AB Intravascular ultrasound (IVUS) has been used for diagnosis of coronary diseases. According to the outstanding transducer performance, Ba0.5Na0.5TiO3 (BNT)-based piezoelectric materials are good candidates for the IVUS applications. In this paper, lead-free BNT piezoelectric thick film has been used to fabricate a linear array transducer. The BNT based transducer array has a 2 x 16-element pattern. In the fabrication process of transducers, micro-machining technologies have been adopted. Wet etching was used to pattern the silicon substrate. The thin layers of Si3N4 and SiO2, are used as etching masks, and patterned by reactive etching and buffered oxide etch (BOE), respectively. After that, the part of Si not covered by the patterned masks is etched by 30% KOH solution. BNT slurry prepared by mixing BNT solution and BNT powder has been deposited on the substrate by spin coating and then thermally treated to obtain the thick film. The PiezoCAD software has been employed to analyze the performance of the array, and the simulation results show that the BNT film array has a center frequency of 82.84 MHz and a -6 dB bandwidth of 46.77%. (C) 2015 Elsevier Ltd and Techna Group S.r.l. All rights reserved.
C1 [Liu, Hongwei; Ren, Wei; Zhao, Jinyan; Zhao, Huifeng; Wu, Xiaoqing; Shi, Peng] Xi An Jiao Tong Univ, Minist Educ, Key Lab, Elect Mat Res Lab, Xian 710049, Peoples R China.
[Liu, Hongwei; Ren, Wei; Zhao, Jinyan; Zhao, Huifeng; Wu, Xiaoqing; Shi, Peng] Xi An Jiao Tong Univ, Int Ctr Dielect Res, Xian 710049, Peoples R China.
[Zhou, Qifa; Shung, K. Kirk] Univ So Calif, Dept Biomed Engn, NIH, Transducer Resource Ctr, Los Angeles, CA 90089 USA.
RP Ren, W (reprint author), Xi An Jiao Tong Univ, Minist Educ, Key Lab, Elect Mat Res Lab, Xian 710049, Peoples R China.
EM wren@mail.xjtu.edu.cn
RI shi, peng/C-8551-2011
OI shi, peng/0000-0003-2217-8486
FU National Natural Science Foundation of China [51332003, 51202184];
International Science & Technology Cooperation Program of China
[2010DFB13640, 2011DFA51880]
FX The authors would like to thank the National Natural Science Foundation
of China, under Grant nos. 51332003 and 51202184, and the International
Science & Technology Cooperation Program of China under Grant nos.
2010DFB13640 and 2011DFA51880 for their financial support.
NR 25
TC 0
Z9 0
U1 6
U2 34
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0272-8842
EI 1873-3956
J9 CERAM INT
JI Ceram. Int.
PD NOV
PY 2015
VL 41
SU 1
BP S631
EP S637
DI 10.1016/j.ceramint.2015.03.256
PG 7
WC Materials Science, Ceramics
SC Materials Science
GA CO2EF
UT WOS:000358968100111
ER
PT J
AU Sun, YY
Birnbaumer, L
Singh, BB
AF Sun, Yuyang
Birnbaumer, Lutz
Singh, Brij B.
TI TRPC1 regulates calcium-activated chloride channels in salivary gland
cells
SO JOURNAL OF CELLULAR PHYSIOLOGY
LA English
DT Article
ID FLUID SECRETION; ACINAR-CELLS; CL-CHANNELS; CA2+ INFLUX; TMEM16A;
PROTEIN; MODULATION; EXPRESSION; MICE
AB Calcium-activated chloride channel (CaCC) plays an important role in modulating epithelial secretion. It has been suggested that in salivary tissues, sustained fluid secretion is dependent on Ca2+ influx that activates ion channels such as CaCC to initiate Cl- efflux. However direct evidence as well as the molecular identity of the Ca2+ channel responsible for activating CaCC in salivary tissues is not yet identified. Here we provide evidence that in human salivary cells, an outward rectifying Cl- current was activated by increasing [Ca2+](i), which was inhibited by the addition of pharmacological agents niflumic acid (NFA), an antagonist of CaCC, or T16Ainh-A01, a specific TMEM16a inhibitor. Addition of thapsigargin (Tg), that induces store-depletion and activates TRPC1-mediated Ca2+ entry, potentiated the Cl- current, which was inhibited by the addition of a non-specific TRPC channel blocker SKF96365 or removal of external Ca2+. Stimulation with Tg also increased plasma membrane expression of TMEM16a protein, which was also dependent on Ca2+ entry. Importantly, in salivary cells, TRPC1 silencing, but not that of TRPC3, inhibited CaCC especially upon store depletion. Moreover, primary acinar cells isolated from submandibular gland also showed outward rectifying Cl- currents upon increasing [Ca2+](i). These Cl- currents were again potentiated with the addition of Tg, but inhibited in the presence of T16Ainh-A01. Finally, acinar cells isolated from the submandibular glands of TRPC1 knockout mice showed significant inhibition of the outward Cl- currents without decreasing TMEM16a expression. Together the data suggests that Ca2+ entry via the TRPC1 channels is essential for the activation of CaCC. J. Cell. Physiol. 9999: 2848-2856, 2015. (c) 2015 Wiley Periodicals, Inc.
C1 [Sun, Yuyang; Singh, Brij B.] Univ N Dakota, Sch Med & Hlth Sci, Dept Basic Sci, Grand Forks, ND 58201 USA.
[Birnbaumer, Lutz] NIHES, Lab Signal Transduct, NIH, Res Triangle Pk, NC USA.
RP Singh, BB (reprint author), Univ N Dakota, Sch Med & Hlth Sci, Dept Basic Sci, Grand Forks, ND 58201 USA.
EM brij.singh@med.und.edu
FU National Institutes of Health [DE017102]; Intramural Research Program of
the NIH [Z01-ES-101684]
FX Contract grant sponsor: National Institutes of Health;; Contract grant
number: DE017102.; Contract grant sponsor: Intramural Research Program
of the NIH;; Contract grant number: Z01-ES-101684.
NR 34
TC 4
Z9 4
U1 3
U2 11
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0021-9541
EI 1097-4652
J9 J CELL PHYSIOL
JI J. Cell. Physiol.
PD NOV
PY 2015
VL 230
IS 11
BP 2848
EP 2856
DI 10.1002/jcp.25017
PG 9
WC Cell Biology; Physiology
SC Cell Biology; Physiology
GA CN8LS
UT WOS:000358692700028
PM 25899321
ER
PT J
AU Naeem, MA
Gottsch, ADH
Ullah, I
Khan, SN
Husnain, T
Butt, NH
Qazi, ZA
Akram, J
Riazuddin, S
Ayyagari, R
Hejtmancik, JF
Riazuddin, SA
AF Naeem, Muhammad Asif
Gottsch, Alexander D. H.
Ullah, Inayat
Khan, Shaheen N.
Husnain, Tayyab
Butt, Nadeem H.
Qazi, Zaheeruddin A.
Akram, Javed
Riazuddin, Sheikh
Ayyagari, Radha
Hejtmancik, J. Fielding
Riazuddin, S. Amer
TI Mutations in GRM6 identified in consanguineous Pakistani families with
congenital stationary night blindness
SO MOLECULAR VISION
LA English
DT Article
ID MISSENSE MUTATION; COMPLETE FORM; GENE; RICH; ELECTRORETINOGRAM;
RESPONSES; SEQUENCE; PROTEIN; GPR179; NYX
AB Purpose: This study was undertaken to investigate the causal mutations responsible for autosomal recessive congenital stationary night blindness (CSNB) in consanguineous Pakistani families.
Methods: Two consanguineous families with multiple individuals manifesting symptoms of stationary night blindness were recruited. Affected individuals underwent a detailed ophthalmological examination, including fundus examination and electroretinography. Blood samples were collected and genomic DNA was extracted. Exclusion analyses were completed by genotyping closely spaced microsatellite markers, and two-point logarithm of odds (LOD) scores were calculated. All coding exons, along with the exon-intron boundaries of GRM6, were sequenced bidirectionally.
Results: According to the medical history available to us, affected individuals in both families had experienced night blindness from the early years of their lives. Fundus photographs of affected individuals in both the families appeared normal, with no signs of attenuated arteries or bone spicule pigmentation. The scotopic electroretinogram (ERG) response were absent in all of the affected individuals, while the photopic measurements show reduced b-waves. During exclusion analyses, both families localized to a region on chromosome 5q that harbors GRM6, a gene previously associated with autosomal recessive CSNB. Bidirectional sequencing of GRM6 identified homozygous single base pair changes, specifically c.1336C>T (p.R446X) and c.2267G>A (p.G756D) in families PKRP170 and PKRP172, respectively.
Conclusions: We identified a novel nonsense and a previously reported missense mutation in GRM6 that were responsible for autosomal recessive CSNB in patients of Pakistani decent.
C1 [Naeem, Muhammad Asif; Ullah, Inayat; Khan, Shaheen N.; Husnain, Tayyab; Riazuddin, Sheikh] Univ Punjab, Natl Ctr Excellence Mol Biol, Lahore, Pakistan.
[Gottsch, Alexander D. H.; Riazuddin, S. Amer] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, 600 N Wolfe St,Maumenee 840, Baltimore, MD 21287 USA.
[Butt, Nadeem H.; Akram, Javed; Riazuddin, Sheikh] Univ Hlth Sci, Allama Iqbal Med Coll, Lahore, Pakistan.
[Qazi, Zaheeruddin A.] Layton Rahmatulla Benevolent Trust Hosp, Lahore, Pakistan.
[Akram, Javed; Riazuddin, Sheikh] Shaheed Zulfiqar Ali Bhutto Med Univ, Natl Ctr Genet Dis, Islamabad, Pakistan.
[Ayyagari, Radha] Univ Calif San Diego, Shiley Eye Inst, La Jolla, CA 92093 USA.
[Hejtmancik, J. Fielding] NEI, NIH, Ophthalm Genet & Visual Funct Branch, Bethesda, MD 20892 USA.
RP Riazuddin, SA (reprint author), Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, 600 N Wolfe St,Maumenee 840, Baltimore, MD 21287 USA.
EM riazuddin@jhmi.edu
FU Higher Education Commission (HEC), Islamabad, Pakistan; Ministry of
Science and Technology, Islamabad, Pakistan; National Eye Institute
[R01EY021237]
FX We are thankful to all family members for their participation in this
study. We are also thankful to the staff of Layton Rehmatulla Benevolent
Trust (LRBT) hospital for clinical evaluation of affected individuals.
This study was supported in part by Higher Education Commission (HEC),
Islamabad, Pakistan, Ministry of Science and Technology, Islamabad,
Pakistan, and National Eye Institute Grant R01EY021237 (RA & SAR).
NR 30
TC 2
Z9 2
U1 0
U2 1
PU MOLECULAR VISION
PI ATLANTA
PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E,
ATLANTA, GA 30322 USA
SN 1090-0535
J9 MOL VIS
JI Mol. Vis.
PD OCT 31
PY 2015
VL 21
BP 1261
EP 1271
PG 11
WC Biochemistry & Molecular Biology; Ophthalmology
SC Biochemistry & Molecular Biology; Ophthalmology
GA DC4FC
UT WOS:000369174900001
PM 26628857
ER
PT J
AU Gara, SK
Wang, YH
Patel, D
Liu-Chittenden, Y
Jain, M
Boufraqech, M
Zhang, LS
Meltzer, PS
Kebebew, E
AF Gara, Sudheer Kumar
Wang, Yonghong
Patel, Dhaval
Liu-Chittenden, Yi
Jain, Meenu
Boufraqech, Myriem
Zhang, Lisa
Meltzer, Paul S.
Kebebew, Electron
TI Integrated genome-wide analysis of genomic changes and gene regulation
in human adrenocortical tissue samples
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID PANCREATIC DUCTAL ADENOCARCINOMA; TUMOR-SUPPRESSOR GENE; BREAST-CANCER
CELLS; P53 MUTATIONS; MOLECULAR CLASSIFICATION; BETA-CATENIN; ONCOSTATIN
M; CARCINOMA; EXPRESSION; TUMORIGENESIS
AB To gain insight into the pathogenesis of adrenocortical carcinoma (ACC) and whether there is progression from normal-to-adenoma-to-carcinoma, we performed genome-wide gene expression, gene methylation, microRNA expression and comparative genomic hybridization (CGH) analysis in human adrenocortical tissue (normal, adrenocortical adenomas and ACC) samples. A pairwise comparison of normal, adrenocortical adenomas and ACC gene expression profiles with more than four-fold expression differences and an adjusted P-value < 0.05 revealed no major differences in normal versus adrenocortical adenoma whereas there are 808 and 1085, respectively, dysregulated genes between ACC versus adrenocortical adenoma and ACC versus normal. The majority of the dysregulated genes in ACC were downregulated. By integrating the CGH, gene methylation and expression profiles of potential miRNAs with the gene expression of dysregulated genes, we found that there are higher alterations in ACC versus normal compared to ACC versus adrenocortical adenoma. Importantly, we identified several novel molecular pathways that are associated with dysregulated genes and further experimentally validated that oncostatin m signaling induces caspase 3 dependent apoptosis and suppresses cell proliferation. Finally, we propose that there is higher number of genomic changes from normal-to-adenoma-to-carcinoma and identified oncostatin m signaling as a plausible druggable pathway for therapeutics.
C1 [Gara, Sudheer Kumar; Patel, Dhaval; Liu-Chittenden, Yi; Jain, Meenu; Boufraqech, Myriem; Zhang, Lisa; Kebebew, Electron] NCI, Endocrine Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Wang, Yonghong; Meltzer, Paul S.] NCI, Genet Branch, NIH, Bethesda, MD 20892 USA.
RP Kebebew, E (reprint author), NCI, Endocrine Oncol Branch, NIH, Bethesda, MD 20892 USA.
EM kebebewe@mail.nih.gov
RI Gara, Sudheer Kumar/E-8084-2016; Boufraqech, Myriem/E-4823-2016;
OI Liu-Chittenden, Yi/0000-0001-6357-5360; Patel,
Dhaval/0000-0002-5744-568X
FU Center for Cancer Research; National Cancer Institute; National
Institutes of Health [1 ZIA BC011275 05]
FX Intramural research program of the Center for Cancer Research; National
Cancer Institute; National Institutes of Health [1 ZIA BC011275 05].
Funding for open access charge: Intramural research program of the
Center for Cancer Research; National Cancer Institute; National
Institutes of Health [1 ZIA BC011275 05].
NR 49
TC 4
Z9 4
U1 0
U2 2
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
EI 1362-4962
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD OCT 30
PY 2015
VL 43
IS 19
BP 9327
EP 9339
DI 10.1093/nar/gkv908
PG 13
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA CY4VA
UT WOS:000366405600024
PM 26446994
ER
PT J
AU Sambuughin, N
Goldfarb, LG
Sivtseva, TM
Davydova, TK
Vladimirtsev, VA
Osakovskiy, VL
Danilova, AP
Nikitina, RS
Ylakhova, AN
Diachkovskaya, MP
Sundborger, AC
Renwick, NM
Platonov, FA
Hinshaw, JE
Toro, C
AF Sambuughin, Nyamkhishig
Goldfarb, Lev G.
Sivtseva, Tatiana M.
Davydova, Tatiana K.
Vladimirtsev, Vsevolod A.
Osakovskiy, Vladimir L.
Danilova, Al'bina P.
Nikitina, Raisa S.
Ylakhova, Anastasia N.
Diachkovskaya, Margarita P.
Sundborger, Anna C.
Renwick, Neil M.
Platonov, Fyodor A.
Hinshaw, Jenny E.
Toro, Camilo
TI Adult-onset autosomal dominant spastic paraplegia linked to a
GTPase-effector domain mutation of dynamin 2
SO BMC NEUROLOGY
LA English
DT Article
DE Paraplegia; HSP; Dynamin; DNM2; Neuropathy; Exome sequencing;
Endocytosis
ID MARIE-TOOTH NEUROPATHY; CENTRONUCLEAR MYOPATHY; MUSCLE INVOLVEMENT;
I-TASSER; VARIANTS; PREDICTION; SPECTRUM; DISEASE; MODEL; SPG3A
AB Background: Hereditary Spastic Paraplegia (HSP) represents a large group of clinically and genetically heterogeneous disorders linked to over 70 different loci and more than 60 recognized disease-causing genes. A heightened vulnerability to disruption of various cellular processes inherent to the unique function and morphology of corticospinal neurons may account, at least in part, for the genetic heterogeneity.
Methods: Whole exome sequencing was utilized to identify candidate genetic variants in a four-generation Siberian kindred that includes nine individuals showing clinical features of HSP. Segregation of candidate variants within the family yielded a disease-associated mutation. Functional as well as in-silico structural analyses confirmed the selected candidate variant to be causative.
Results: Nine known patients had young-adult onset of bilateral slowly progressive lower-limb spasticity, weakness and hyperreflexia progressing over two-to-three decades to wheel-chair dependency. In the advanced stage of the disease, some patients also had distal wasting of lower leg muscles, pes cavus, mildly decreased vibratory sense in the ankles, and urinary urgency along with electrophysiological evidence of a mild distal motor/sensory axonopathy. Molecular analyses uncovered a missense c. 2155C > T, p. R719W mutation in the highly conserved GTP-effector domain of dynamin 2. The mutant DNM2 co-segregated with HSP and affected endocytosis when expressed in HeLa cells. In-silico modeling indicated that this HSP-associated dynamin 2 mutation is located in a highly conserved bundle-signaling element of the protein while dynamin 2 mutations associated with other disorders are located in the stalk and PH domains; p. R719W potentially disrupts dynamin 2 assembly.
Conclusion: This is the first report linking a mutation in dynamin 2 to a HSP phenotype. Dynamin 2 mutations have previously been associated with other phenotypes including two forms of Charcot-Marie-Tooth neuropathy and centronuclear myopathy. These strikingly different pathogenic effects may depend on structural relationships the mutations disrupt. Awareness of this distinct association between HSP and c. 2155C > T, p. R719W mutation will facilitate ascertainment of additional DNM2 HSP families and will direct future research toward better understanding of cell biological processes involved in these partly overlapping clinical syndromes.
C1 [Sambuughin, Nyamkhishig] Uniformed Serv Univ Hlth Sci, Consortium Hlth & Mil Performance, Bethesda, MD 20814 USA.
[Goldfarb, Lev G.] NINDS, NIH, Bethesda, MD 20892 USA.
[Sivtseva, Tatiana M.; Davydova, Tatiana K.; Vladimirtsev, Vsevolod A.; Osakovskiy, Vladimir L.; Danilova, Al'bina P.; Nikitina, Raisa S.; Ylakhova, Anastasia N.; Diachkovskaya, Margarita P.; Platonov, Fyodor A.] MK Ammosov North Eastern Fed Univ, Inst Hlth, Yakutsk 677010, Russia.
[Sundborger, Anna C.; Hinshaw, Jenny E.] NIDDK, NIH, Bethesda, MD 20892 USA.
[Renwick, Neil M.] Queens Univ, Kingston Gen Hosp, Dept Pathol & Mol Med, Kingston, ON K7L 3N6, Canada.
[Toro, Camilo] NHGRI, NIH, Bethesda, MD 20892 USA.
RP Goldfarb, LG (reprint author), NINDS, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
EM GoldfarbL@ninds.nih.gov
RI Sundborger, Anna/J-6590-2014
OI Sundborger, Anna/0000-0003-4696-7543
FU Ministry of Education and Science of the Russian Federation [3095];
Uniformed Services University (USU) [R080148613]; National Institute of
Neurological Disorders and Stroke, NIH; National Institute of Diabetes,
Digestive and Kidney Diseases, NIH; National Human Genome Research
Institute, NIH
FX We wish to thank Dr. C. Merrifield for providing the cloned wild-type
human DNM2 and Dr. W. Gall for helpful comments and suggestions. The
study was funded in part by the Ministry of Education and Science of the
Russian Federation (project No. 3095). Research was supported by the
Uniformed Services University (USU) R080148613 grant to N.S., Intramural
Research Programs of the National Institute of Neurological Disorders
and Stroke, the National Institute of Diabetes, Digestive and Kidney
Diseases, and the National Human Genome Research Institute, NIH.
Technical support was provided by the NIH Intramural Sequencing Center
(NISC), Bioinformatics core of the NIH Undiagnosed Diseases Program, and
the Biomedical Instrumentation Center of USU.
NR 43
TC 1
Z9 1
U1 2
U2 4
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2377
J9 BMC NEUROL
JI BMC Neurol.
PD OCT 30
PY 2015
VL 15
AR 223
DI 10.1186/s12883-015-0481-3
PG 12
WC Clinical Neurology
SC Neurosciences & Neurology
GA CW9CN
UT WOS:000365296100002
PM 26517984
ER
PT J
AU Appella, E
Jenkins, LMM
Guengerich, FP
AF Appella, Ettore
Jenkins, Lisa M. Miller
Guengerich, F. Peter
TI Introduction to Thematic Series: Protein Interactions, Structures, and
Networks
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Editorial Material
AB Protein interactions are fundamental to the proper functioning of cells, and aberrant formation or regulation of protein interactions is at the heart of many diseases, including cancer. The advancement of methods to study the identity, function, and regulation of protein complexes makes possible the understanding of how those complexes malfunction in human diseases. New methodologies in mass spectrometry, microscopy, and protein structural analysis are rapidly advancing the amount and quality of the data, as well as the level of detail that can be obtained from experiments. With this progress, the questions that can be addressed and the biological landscape are changing. This series of minireviews highlights methodological advances and how they have been applied in novel ways to explore the function and regulation of pathways and dynamic networks in cells.
C1 [Appella, Ettore; Jenkins, Lisa M. Miller] NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA.
[Guengerich, F. Peter] Vanderbilt Univ, Sch Med, Dept Biochem, Nashville, TN 37232 USA.
RP Appella, E (reprint author), NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA.
EM appellae@mail.nih.gov
NR 6
TC 0
Z9 0
U1 3
U2 5
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD OCT 30
PY 2015
VL 290
IS 44
BP 26393
EP 26394
DI 10.1074/jbc.R115.690370
PG 2
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA CW2AO
UT WOS:000364793600005
PM 26354433
ER
PT J
AU Balagopalan, L
Kortum, RL
Coussens, NP
Barr, VA
Samelson, LE
AF Balagopalan, Lakshmi
Kortum, Robert L.
Coussens, Nathan P.
Barr, Valarie A.
Samelson, Lawrence E.
TI The Linker for Activation of T Cells (LAT) Signaling Hub: From Signaling
Complexes to Microclusters
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Review
ID ANTIGEN RECEPTOR; MULTIPOINT BINDING; TYROSINE RESIDUES; PROTEIN
COMPLEXES; LIPID RAFTS; GRB2; DOMAINS; SLP-76; PLC-GAMMA-1; RECRUITMENT
AB Since the cloning of the critical adapter, LAT (linker for activation of T cells), more than 15 years ago, a combination of multiple scientific approaches and techniques continues to provide valuable insights into the formation, composition, regulation, dynamics, and function of LAT-based signaling complexes. In this review, we will summarize current views on the assembly of signaling complexes nucleated by LAT. LAT forms numerous interactions with other signaling molecules, leading to cooperativity in the system. Furthermore, oligomerization of LAT by adapter complexes enhances intracellular signaling and is physiologically relevant. These results will be related to data from super-resolution microscopy studies that have revealed the smallest LAT-based signaling units and nanostructure.
C1 [Balagopalan, Lakshmi] NCI, Cellular & Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Kortum, Robert L.] Uniformed Serv Univ Hlth Sci, Dept Pharmacol, Bethesda, MD 20814 USA.
[Coussens, Nathan P.] NIH, Div Preclin Innovat, Natl Ctr Adv Translat Sci, Rockville, MD 20850 USA.
EM samelsonl@helix.nih.gov
FU Intramural Research Program of the National Institutes of Health, NCI,
Center for Cancer Research (CCR)
FX This work was supported by the Intramural Research Program of the
National Institutes of Health, NCI, Center for Cancer Research (CCR).
This is the fourth article in the Thematic Minireview series "Protein
Interactions, Structures, and Networks." The authors declare that they
have no conflicts of interest with the contents of this article.
NR 64
TC 7
Z9 7
U1 1
U2 5
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD OCT 30
PY 2015
VL 290
IS 44
BP 26422
EP 26429
DI 10.1074/jbc.R115.665869
PG 8
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA CW2AO
UT WOS:000364793600009
PM 26354432
ER
PT J
AU Blasic, JR
Worcester, DL
Gawrisch, K
Gurnev, P
Mihailescu, M
AF Blasic, Joseph R.
Worcester, David L.
Gawrisch, Klaus
Gurnev, Philip
Mihailescu, Mihaela
TI Pore Hydration States of KcsA Potassium Channels in Membranes
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID BILAYER STRUCTURE DETERMINATION; NEUTRON-DIFFRACTION DATA; INFLUENZA-A
VIRUS; K+ CHANNEL; X-RAY; CRYSTAL-STRUCTURE; CYTOCHROME P450CAM; JOINT
REFINEMENT; VOLUME CHANGES; ION-CHANNEL
AB Water-filled hydrophobic cavities in channel proteins serve as gateways for transfer of ions across membranes, but their properties are largely unknown. We determined water distributions along the conduction pores in two tetrameric channels embedded in lipid bilayers using neutron diffraction: potassium channel KcsA and the transmembrane domain of M2 protein of influenza A virus. For the KcsA channel in the closed state, the distribution of water is peaked in the middle of the membrane, showing water in the central cavity adjacent to the selectivity filter. This water is displaced by the channel blocker tetrabutylammonium. The amount of water associated with the channel was quantified, using neutron diffraction and solid state NMR. In contrast, the M2 proton channel shows a V-shaped water profile across the membrane, with a narrow constriction at the center, like the hourglass shape of its internal surface. These two types of water distribution are therefore very different in their connectivity to the bulk water. The water and protein profiles determined here provide important evidence concerning conformation and hydration of channels in membranes and the potential role of pore hydration in channel gating.
C1 [Blasic, Joseph R.; Mihailescu, Mihaela] Univ Maryland, Inst Biosci & Biotechnol Res, Rockville, MD 20850 USA.
[Worcester, David L.] Univ Calif Irvine, Dept Physiol & Biophys, Irvine, CA 92697 USA.
[Worcester, David L.] NIST, Ctr Neutron Res, Gaithersburg, MD 20899 USA.
[Gawrisch, Klaus] NIAAA, Lab Membrane Biochem & Biophys, NIH, Bethesda, MD 20892 USA.
[Gurnev, Philip] Univ Massachusetts, Dept Phys, Amherst, MA 01003 USA.
[Gurnev, Philip] NICHHD, NIH, Bethesda, MD 20892 USA.
RP Mihailescu, M (reprint author), Univ Maryland, Inst Biosci & Biotechnol Res, 9600 Gudelsky Dr, Rockville, MD 20850 USA.
EM emihailescu@ibbr.umd.edu
FU National Research Council; NIST Biomanufacturing Initiative
FX We thank Crina Nimigean for providing the KcsA plasmid and Jun Wang and
William F. DeGrado for the M2 peptide. We also thank Kenton Swartz,
Dmitriy Krepkiy (NINDS, National Institutes of Health), and Stephen H.
White (University of California, Irvine) for helpful discussions. We
acknowledge the National Research Council for the postdoctoral
fellowship awarded to J. B. We acknowledge the National Institute of
Standards and Technology, U.S. Department of Commerce, in providing the
neutron research facilities and the support provided by NIST
Biomanufacturing Initiative. The identification of any commercial
product or trade name does not imply endorsement or recommendation by
the National Institute of Standards and Technology.
NR 43
TC 1
Z9 1
U1 4
U2 13
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD OCT 30
PY 2015
VL 290
IS 44
BP 26765
EP U472
DI 10.1074/jbc.M115.661819
PG 13
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA CW2AO
UT WOS:000364793600038
PM 26370089
ER
PT J
AU Sheldon, KL
Gurnev, PA
Bezrukov, SM
Sackett, DL
AF Sheldon, Kely L.
Gurnev, Philip A.
Bezrukov, Sergey M.
Sackett, Dan L.
TI Tubulin Tail Sequences and Post-translational Modifications Regulate
Closure of Mitochondrial Voltage-dependent Anion Channel (VDAC)
SO JOURNAL OF BIOLOGICAL CHEMISTRY
LA English
DT Article
ID ALPHA-HEMOLYSIN; MEMBRANE; POLYMERIZATION; TERMINI; CELLS; PORE
AB It was previously shown that tubulin dimer interaction with the mitochondrial outer membrane protein voltage-dependent anion channel (VDAC) blocks traffic through the channel and reduces oxidative metabolism and that this requires the unstructured anionic C-terminal tail peptides found on both alpha- and beta-tubulin subunits. It was unclear whether the alpha- and beta-tubulin tails contribute equally to VDAC blockade and what effects might be due to sequence variations in these tail peptides or to tubulin post-translational modifications, which mostly occur on the tails. The nature of the contribution of the tubulin body beyond acting as an anchor for the tails had not been clarified either. Here we present peptide-protein chimeras to address these questions. These constructs allow us to easily combine a tail peptide with different proteins or combine different tail peptides with a particular protein. The results show that a single tail grafted to an inert protein is sufficient to produce channel closure similar to that observed with tubulin. We show that the beta-tail is more than an order of magnitude more potent than the alpha-tail and that the lower alpha-tail activity is largely due to the presence of a terminal tyrosine. Detyrosination activates the alpha-tail, and activation is reversed by the removal of the glutamic acid penultimate to the tyrosine. Nitration of tyrosine reverses the tyrosine inhibition of binding and even induces prolonged VDAC closures. Our results demonstrate that small changes in sequence or post-translational modification of the unstructured tails of tubulin result in substantial changes in VDAC closure.
C1 [Sheldon, Kely L.; Gurnev, Philip A.; Bezrukov, Sergey M.; Sackett, Dan L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Phys Biol, NIH, Bethesda, MD 20892 USA.
RP Sheldon, KL (reprint author), Emory Univ, Div Cardiol, Dept Med, Sch Med, 307 Woodruff Mem Bldg,1639 Pierce Dr, Atlanta, GA 30322 USA.
EM ksheldo@emory.edu; sackettd@mail.nih.gov
FU Intramural Research Program of the Eunice Kennedy Shriver National
Institute of Child Health and Human Development, National Institutes of
Health, Bethesda, MD
FX This work was supported by the Intramural Research Program of the Eunice
Kennedy Shriver National Institute of Child Health and Human
Development, National Institutes of Health, Bethesda, MD. The authors
declare that they have no conflicts of interest with the contents of
this article.
NR 25
TC 2
Z9 2
U1 1
U2 2
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0021-9258
EI 1083-351X
J9 J BIOL CHEM
JI J. Biol. Chem.
PD OCT 30
PY 2015
VL 290
IS 44
BP 26784
EP 26789
DI 10.1074/jbc.M115.678854
PG 6
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA CW2AO
UT WOS:000364793600040
PM 26306046
ER
PT J
AU Oh, J
Chun, JW
Jo, HJ
Kim, E
Park, HJ
Lee, B
Kim, JJ
AF Oh, Jooyoung
Chun, Ji-Won
Jo, Hang Joon
Kim, Eunseong
Park, Hae-Jeong
Lee, Boreom
Kim, Jae-Jin
TI The neural basis of a deficit in abstract thinking in patients with
schizophrenia
SO PSYCHIATRY RESEARCH-NEUROIMAGING
LA English
DT Article
DE Abstract thinking; Theme identification; Schizophrenia; Frontopolar
cortex; Orbitofrontal cortex; FMRI
ID NEAR-INFRARED SPECTROSCOPY; REDUCED FRONTOPOLAR ACTIVATION; DORSOLATERAL
PREFRONTAL CORTEX; VERBAL FLUENCY TASK; WORKING-MEMORY;
NEURODEVELOPMENTAL HYPOTHESIS; PHYSIOLOGICAL DYSFUNCTION; COGNITIVE
CONTROL; SOCIAL COGNITION; CONCRETE
AB Abnormal abstract thinking is a major cause of social dysfunction in patients with schizophrenia, but little is known about its neural basis. In this study, we aimed to determine the characteristic abstract thinking-related brain responses in patients using a task reflecting social situations. We conducted functional magnetic resonance imaging while 16 patients with schizophrenia and 16 healthy controls performed a theme-identification task, in which various emotional pictures depicting social situations were presented. Compared with healthy controls, the patients showed significantly decreased activity in the left frontopolar and right orbitofrontal cortices during theme identification. Activity in these two regions correlated well in the controls, but not in patients. Instead, the patients exhibited a close correlation between activity in both sides of the frontopolar cortex, and a positive correlation between the right orbitofrontal cortex activity and degrees of theme identification. Reduced activity in the left frontopolar and right orbitofrontal cortices and the underlying aberrant connectivity may be implicated in the patients' deficits in abstract thinking. These newly identified features of the neural basis of abnormal abstract thinking are important as they have implications for the impaired social behavior of patients with schizophrenia during real-life situations. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
C1 [Oh, Jooyoung; Lee, Boreom] Gwangju Inst Sci & Technol, DMSE, Gwangju 500712, South Korea.
[Chun, Ji-Won; Kim, Eunseong; Kim, Jae-Jin] Yonsei Univ, Coll Med, Inst Behav Sci Med, Seoul, South Korea.
[Jo, Hang Joon] NIMH, Sect Funct Imaging Methods, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA.
[Park, Hae-Jeong] Yonsei Univ, Coll Med, Dept Nucl Med, Seoul, South Korea.
[Lee, Boreom] Gwangju Inst Sci & Technol, Sch Mechatron, Gwangju 500712, South Korea.
[Kim, Jae-Jin] Yonsei Univ, Coll Med, Dept Psychiat, Seoul, South Korea.
RP Lee, B (reprint author), Gwangju Inst Sci & Technol, DMSE, 123 Cheomdangwagi Ro, Gwangju 500712, South Korea.
EM leebr@gist.ac.kr; jaekim@yonsei.ac.kr
OI Jo, Hang Joon/0000-0002-9180-3831
FU Institute of Medical System Engineering (iMSE) in the GIST, Korea;
National Research Foundation of Korea (NRF) - Korea government (MEST)
[NRF-2013R1A2A2A03068342]
FX The research was supported by a grant from the Institute of Medical
System Engineering (iMSE) in the GIST, Korea, and was supported by the
National Research Foundation of Korea (NRF) grant funded by the Korea
government (MEST) (No. NRF-2013R1A2A2A03068342).
NR 57
TC 1
Z9 2
U1 4
U2 10
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0925-4927
EI 1872-7506
J9 PSYCHIAT RES-NEUROIM
JI Psychiatry Res. Neuroimaging
PD OCT 30
PY 2015
VL 234
IS 1
BP 66
EP 73
DI 10.1016/j.pscychresns.2015.08.007
PG 8
WC Clinical Neurology; Neuroimaging; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA CW8AT
UT WOS:000365221500009
PM 26329118
ER
PT J
AU Ruszkowski, M
Nocek, B
Forlani, G
Dauter, Z
AF Ruszkowski, Milosz
Nocek, Boguslaw
Forlani, Giuseppe
Dauter, Zbigniew
TI The structure of Medicago truncatula delta(1)-pyrroline-5-carboxylate
reductase provides new insights into regulation of proline biosynthesis
in plants
SO FRONTIERS IN PLANT SCIENCE
LA English
DT Article
DE protein structure; decamer; coenzyme preference; salt stress; abiotic
stress; P5C reductase; P5CR
ID OSMOTIC-STRESS; PYRROLINE-5-CARBOXYLATE REDUCTASE;
STREPTOCOCCUS-PYOGENES; ARABIDOPSIS-THALIANA; ENHANCED TOLERANCE;
CRYSTAL-STRUCTURES; SYNTHETASE GENE; P5C REDUCTASE; ROOT-NODULES;
ACCUMULATION
AB The two pathways for proline biosynthesis in higher plants share the last step, the conversion of delta(1)-pyrroline-5-carboxylate (P5C) to L-proline, which is catalyzed by P5C reductase (P5OR, EC 1.5.1.2) with the use of NAD(P)H as a coenzyme. There is increasing amount of evidence to suggest a complex regulation of P5CR activity at the post-translational level, yet the molecular basis of these mechanisms is unknown. Here we report the three-dimensional structure of the P5CR enzyme from the model legume Medicago truncatula (Mt). The crystal structures of unliganded MtP5CR decamer, and its complexes with the products NAD+, NADP, and L-proline were refined using x-ray diffraction data (at 1.7, 1.85, 1.95, and 2.1 angstrom resolution, respectively). Based on the presented structural data, the coenzyme preference for NADPH over NADH was explained, and NADPH is suggested to be the only coenzyme used by MtP5CR in vivo. Furthermore, the insensitivity of MtP5CR to feed-back inhibition by proline, revealed by enzymatic analysis, was correlated with structural features. Additionally, a mechanism for the modulation of enzyme activity by chloride anions is discussed, as well as the rationale for the possible development of effective enzyme inhibitors.
C1 [Ruszkowski, Milosz; Dauter, Zbigniew] NCI, Synchrotron Radiat Res Sect, Macromol Crystallog Lab, Argonne, IL 60439 USA.
[Nocek, Boguslaw] Argonne Natl Lab, Biosci Div, Struct Biol Ctr, Argonne, IL 60439 USA.
[Forlani, Giuseppe] Univ Ferrara, Dept Life Sci & Biotechnol, I-44100 Ferrara, Italy.
RP Ruszkowski, M (reprint author), NCI, Synchrotron Radiat Res Sect, Macromol Crystallog Lab, Argonne, IL 60439 USA.
EM mruszkowski@anl.gov
RI Forlani, Giuseppe/B-7869-2009
OI Forlani, Giuseppe/0000-0003-2598-5718
FU NCI, Center for Cancer Research; U.S. Department of Energy, Office of
Biological and Environmental Research [DE-AC02-06CH11357]
FX This project was supported in part by the Intramural Research Program of
the NCI, Center for Cancer Research. Structural results shown in this
report are derived from work performed at Argonne National Laboratory,
Structural Biology Center at the Advanced Photon Source. Argonne is
operated by UChicago Argonne, LLC, for the U.S. Department of Energy,
Office of Biological and Environmental Research under contract
DE-AC02-06CH11357.
NR 70
TC 3
Z9 3
U1 3
U2 15
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015,
SWITZERLAND
SN 1664-462X
J9 FRONT PLANT SCI
JI Front. Plant Sci.
PD OCT 30
PY 2015
VL 6
AR 869
DI 10.3389/fpls.2015.00869
PG 17
WC Plant Sciences
SC Plant Sciences
GA CV8ZD
UT WOS:000364576000001
PM 26579138
ER
PT J
AU Dasarathy, D
Ito, Y
AF Dasarathy, Dhweeja
Ito, Yoichiro
TI An improved design of spiral tube assembly for separation of proteins by
high-speed counter-current chromatography
SO JOURNAL OF CHROMATOGRAPHY A
LA English
DT Article
DE Spiral tube assembly; Flat-twisted tubing; High-speed countercurrent
chromatography; Protein separation; Polymer phase system
ID SUPPORT
AB A new spiral tube assembly was designed to improve the column capacity and partition efficiency for protein separation. This spiral tube assembly has greater column capacity than the original tubing because of an increase in radial grooves from 4 to 12 to accommodate more spiral layers and 12 narrow spots instead of 4 in each circular loop to interrupt the laminar flow that causes sample band broadening. Standard PTFE tubing (1.6 mm ID) and the modified flat-twisted tubing were used as the separation column. The performances of both assemblies were compared for separating three stable test proteins including cytochrome c, myoglobin, and lysozyme using a two phase aqueous aqueous solvent system composed of polyethylene glycol 1000 (12.5% w/w) and dibasic potassium phosphate (12.5% w/w). All samples were run at 1, 2, 3, and 5 mL/min at both 800 rpm and 1000 rpm. The separation of these three protein samples produced high stationary phase retentions at 1, 2, and 3 mL/min, yet separated efficiently at 5 mL/min in 40 min. After comparing the separation efficiency in terms of the peak resolutions, theoretical plate numbers, and separation times, it was determined that the flat-twisted tubing was more effective in separating these protein samples. In order to validate the efficacy of this novel assembly, a mixture of five protein samples (cytochrome c, myoglobin, ovalbumin, lysozyme, and hemoglobin) were separated, under the optimal conditions established with these three protein samples, at I mL/min with a revolution speed of 1000 rpm. There were high stationary phase retentions of around 60%, with effective separations, demonstrating the efficiency of the flat-twisted spiral tube assembly. The separation time of 6 h was a limitation but can potentially be shortened by improving the strength of the column that will permit an increase in revolution speed and flow rate. This novel spiral separation column will allow rapid and efficient separation of mixtures with high yield of the constituent components. Published by Elsevier B.V.
C1 [Dasarathy, Dhweeja; Ito, Yoichiro] NHLBI, Lab Bioseparat Technol, Biochem & Biophys Ctr, NIH, Bethesda, MD 20892 USA.
[Dasarathy, Dhweeja] Hawken Sch, Gates Mills, OH 44040 USA.
RP Ito, Y (reprint author), NHLBI, Lab Bioseparat Technol, Biochem & Biophys Ctr, NIH, 10 Ctr Dr,Bldg 10,Rm 8N230, Bethesda, MD 20892 USA.
EM itoy2@mail.nih.gov
FU NHLBI summer internship program
FX The authors thank Dr. Xiaofeng Ma for technical instruction and Dr.
Martha Knight of CCBiotech for preparation and use of the standard
spiral tube assembly. This study is supported by the NHLBI summer
internship program.
NR 17
TC 2
Z9 2
U1 4
U2 22
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0021-9673
EI 1873-3778
J9 J CHROMATOGR A
JI J. Chromatogr. A
PD OCT 30
PY 2015
VL 1418
BP 77
EP 82
DI 10.1016/j.chroma.2015.09.033
PG 6
WC Biochemical Research Methods; Chemistry, Analytical
SC Biochemistry & Molecular Biology; Chemistry
GA CV4WW
UT WOS:000364268200008
PM 26427324
ER
PT J
AU Bis, JC
Sitlani, C
Irvin, R
Avery, CL
Smith, AV
Sun, FG
Evans, DS
Musani, SK
Li, XH
Trompet, S
Krijthe, BP
Harris, TB
Quibrera, PM
Brody, JA
Demissie, S
Davis, BR
Wiggins, KL
Tranah, GJ
Lange, LA
Sotoodehnia, N
Stott, DJ
Franco, OH
Launer, LJ
Sturmer, T
Taylor, KD
Cupples, LA
Eckfeldt, JH
Smith, NL
Liu, YM
Wilson, JG
Heckbert, SR
Buckley, BM
Ikram, MA
Boerwinkle, E
Chen, YDI
de Craen, AJM
Uitterlinden, AG
Rotter, JI
Ford, I
Hofman, A
Sattar, N
Slagboom, PE
Westendorp, RGJ
Gudnason, V
Vasan, RS
Lumley, T
Cummings, SR
Taylor, HA
Post, W
Jukema, JW
Stricker, BH
Whitsel, EA
Psaty, BM
Arnett, D
AF Bis, Joshua C.
Sitlani, Colleen
Irvin, Ryan
Avery, Christy L.
Smith, Albert Vernon
Sun, Fangui
Evans, Daniel S.
Musani, Solomon K.
Li, Xiaohui
Trompet, Stella
Krijthe, Bouwe P.
Harris, Tamara B.
Quibrera, P. Miguel
Brody, Jennifer A.
Demissie, Serkalem
Davis, Barry R.
Wiggins, Kerri L.
Tranah, Gregory J.
Lange, Leslie A.
Sotoodehnia, Nona
Stott, David J.
Franco, Oscar H.
Launer, Lenore J.
Stuermer, Til
Taylor, Kent D.
Cupples, L. Adrienne
Eckfeldt, John H.
Smith, Nicholas L.
Liu, Yongmei
Wilson, James G.
Heckbert, Susan R.
Buckley, Brendan M.
Ikram, M. Arfan
Boerwinkle, Eric
Chen, Yii-Der Ida
de Craen, Anton J. M.
Uitterlinden, Andre G.
Rotter, Jerome I.
Ford, Ian
Hofman, Albert
Sattar, Naveed
Slagboom, P. Eline
Westendorp, Rudi G. J.
Gudnason, Vilmundur
Vasan, Ramachandran S.
Lumley, Thomas
Cummings, Steven R.
Taylor, Herman A., Jr.
Post, Wendy
Jukema, J. Wouter
Stricker, Bruno H.
Whitsel, Eric A.
Psaty, Bruce M.
Arnett, Donna
TI Drug-Gene Interactions of Antihypertensive Medications and Risk of
Incident Cardiovascular Disease: A Pharmacogenomics Study from the
CHARGE Consortium
SO PLOS ONE
LA English
DT Article
ID GENOMIC ASSOCIATION ANALYSIS; BLOOD-PRESSURE; ENVIRONMENT INTERACTION;
WIDE ASSOCIATION; HYPERTENSION; OUTCOMES; VARIANTS; HEART; LOCI
AB Background
Hypertension is a major risk factor for a spectrum of cardiovascular diseases (CVD), including myocardial infarction, sudden death, and stroke. In the US, over 65 million people have high blood pressure and a large proportion of these individuals are prescribed antihypertensive medications. Although large long-term clinical trials conducted in the last several decades have identified a number of effective antihypertensive treatments that reduce the risk of future clinical complications, responses to therapy and protection from cardiovascular events vary among individuals.
Methods
Using a genome-wide association study among 21,267 participants with pharmaceutically treated hypertension, we explored the hypothesis that genetic variants might influence or modify the effectiveness of common antihypertensive therapies on the risk of major cardiovascular outcomes. The classes of drug treatments included angiotensin-converting enzyme inhibitors, beta-blockers, calcium channel blockers, and diuretics. In the setting of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, each study performed array-based genome-wide genotyping, imputed to HapMap Phase II reference panels, and used additive genetic models in proportional hazards or logistic regressionmodels to evaluate drug-gene interactions for each of four therapeutic drug classes. We used meta-analysis to combine study-specific interaction estimates for approximately 2 million single nucleotide polymorphisms (SNPs) in a discovery analysis among 15,375 European Ancestry participants (3,527 CVD cases) with targeted follow-up in a case-only study of 1,751 European Ancestry GenHAT participants as well as among 4,141 African-Americans (1,267 CVD cases).
Results
Although drug-SNP interactions were biologically plausible, exposures and outcomes were well measured, and power was sufficient to detect modest interactions, we did not identify any statistically significant interactions from the four antihypertensive therapy meta-analyses (P-interaction > 5.0x10(-8)). Similarly, findings were null for meta-analyses restricted to 66 SNPs with significant main effects on coronary artery disease or blood pressure from large published genome-wide association studies (P-interaction >= 0.01). Our results suggest that there are no major pharmacogenetic influences of common SNPs on the relationship between blood pressure medications and the risk of incident CVD.
C1 [Bis, Joshua C.; Sitlani, Colleen; Brody, Jennifer A.; Wiggins, Kerri L.; Sotoodehnia, Nona; Heckbert, Susan R.; Psaty, Bruce M.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.
[Irvin, Ryan; Arnett, Donna] Univ Alabama Birmingham, Dept Epidemiol, Birmingham, AL USA.
[Avery, Christy L.; Stuermer, Til; Whitsel, Eric A.] Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Epidemiol, Chapel Hill, NC USA.
[Smith, Albert Vernon; Gudnason, Vilmundur] Iceland Heart Assoc, Kopavogur, Iceland.
[Smith, Albert Vernon; Gudnason, Vilmundur] Univ Iceland, Fac Med, Reykjavik, Iceland.
[Sun, Fangui; Demissie, Serkalem; Cupples, L. Adrienne] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Evans, Daniel S.; Tranah, Gregory J.; Cummings, Steven R.] Calif Pacific Med Ctr, Res Inst, San Francisco, CA USA.
[Musani, Solomon K.] Univ Mississippi, Med Ctr, Dept Med, Jackson, MS 39216 USA.
[Li, Xiaohui; Taylor, Kent D.; Chen, Yii-Der Ida; Rotter, Jerome I.] Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Inst Translat Genom & Populat Sci, Torrance, CA 90509 USA.
[Trompet, Stella; Jukema, J. Wouter] Leiden Univ, Med Ctr, Dept Cardiol, NL-2300 RA Leiden, Netherlands.
[Trompet, Stella; de Craen, Anton J. M.] Leiden Univ, Med Ctr, Dept Gerontol & Geriatr, NL-2300 RA Leiden, Netherlands.
[Krijthe, Bouwe P.; Franco, Oscar H.; Ikram, M. Arfan; Uitterlinden, Andre G.; Hofman, Albert; Stricker, Bruno H.] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.
[Harris, Tamara B.; Launer, Lenore J.] Natl Inst Aging, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD USA.
[Quibrera, P. Miguel] Univ N Carolina, Gillings Sch Global Publ Hlth, Collaborat Studies Coordinating Ctr, Chapel Hill, NC USA.
[Davis, Barry R.] Univ Texas Houston, Sch Publ Hlth, Dept Biostat, Houston, TX USA.
[Tranah, Gregory J.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
[Lange, Leslie A.] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA.
[Sotoodehnia, Nona] Univ Washington, Div Cardiol, Seattle, WA 98195 USA.
[Stott, David J.] Univ Glasgow, Fac Med, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland.
[Stuermer, Til] Univ N Carolina, GSK Ctr Excellence Pharmacoepidemiol, Chapel Hill, NC USA.
[Li, Xiaohui; Taylor, Kent D.; Chen, Yii-Der Ida; Rotter, Jerome I.] Harbor UCLA Med Ctr, Dept Pediat, Torrance, CA 90509 USA.
[Cupples, L. Adrienne; Vasan, Ramachandran S.] Framingham Heart Dis Epidemiol Study, Framingham, MA USA.
[Eckfeldt, John H.] Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA.
[Smith, Nicholas L.; Heckbert, Susan R.; Psaty, Bruce M.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Smith, Nicholas L.] Seattle Epidemiol Res & Informat Ctr, Dept Vet Affairs Off Res & Dev, Seattle, WA USA.
[Liu, Yongmei] Wake Forest Univ, Dept Epidemiol & Prevent, Div Publ Hlth Sci, Winston Salem, NC 27109 USA.
[Wilson, James G.] Univ Mississippi, Med Ctr, Dept Physiol & Biophys, Jackson, MS 39216 USA.
[Buckley, Brendan M.] Natl Univ Ireland Univ Coll Cork, Dept Pharmacol & Therapeut, Cork, Ireland.
[Boerwinkle, Eric] Univ Texas Houston, Hlth Sci Ctr, Inst Mol Med, Houston, TX USA.
[Uitterlinden, Andre G.] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands.
[Ford, Ian] Univ Glasgow, Robertson Ctr Biostat, Glasgow, Lanark, Scotland.
[Sattar, Naveed] BHF Glasgow Cardiovasc Res Ctr, Fac Med, Glasgow, Lanark, Scotland.
[Slagboom, P. Eline] Leiden Univ, Med Ctr, Dept Mol Epidemiol, Leiden, Netherlands.
[Westendorp, Rudi G. J.] Univ Copenhagen, Fac Hlth & Med Sci, Dept Publ Hlth, Copenhagen, Denmark.
[Vasan, Ramachandran S.] Boston Univ, Sch Med, Boston, MA 02118 USA.
[Vasan, Ramachandran S.] Boston Univ, Sch Publ Hlth, Boston, MA USA.
[Lumley, Thomas] Univ Auckland, Dept Stat, Auckland 1, New Zealand.
[Taylor, Herman A., Jr.] Morehouse Sch Med, Dept Med, Atlanta, GA 30310 USA.
[Post, Wendy] Johns Hopkins Univ, Dept Med, Div Cardiol, Baltimore, MD USA.
[Stricker, Bruno H.] Inspectorate Hlth Care, The Hague, Netherlands.
[Whitsel, Eric A.] Univ N Carolina, Sch Med, Dept Med, Chapel Hill, NC USA.
[Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA.
[Psaty, Bruce M.] Grp Hlth Res Inst, Grp Hlth, Seattle, WA USA.
RP Psaty, BM (reprint author), Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.
EM psaty@uw.edu
RI Slagboom, P. Eline/R-4790-2016; Smith, Albert Vernon/K-5150-2015;
OI Slagboom, P. Eline/0000-0002-2875-4723; Smith, Albert
Vernon/0000-0003-1942-5845; Ramachandran, Vasan/0000-0001-7357-5970;
Sattar, Naveed/0000-0002-1604-2593
FU National Institutes of Health (NIH) [N01-AG-1-2100]; National Institutes
on Aging (NIA) Intramural Research Program; Hjartavernd (the Icelandic
Heart Association); Althingi (the Icelandic Parliament); National Heart,
Lung, and Blood Institute [HHSN268201100005C, HHSN268201100006C,
HHSN268201100007C, HHSN268201100008C, HHSN268201100009C,
HHSN268201100010C, HHSN268201100011C, HHSN268201100012C, R01HL087641,
R01HL59367, R01HL086694]; National Human Genome Research Institute
[U01HG004402]; National Institutes of Health [HHSN268200625226C,
UL1RR025005, HHSN268200782096C]; NIH Roadmap for Medical Research; NHLBI
[HHSN268201200036C, HHSN268200800007C, N01HC55222, N01HC85079,
N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086, U01HL080295,
R01HL087652, R01HL105756, R01HL103612, R01HL120393,
N02-HL-6-4278HL085251, HL073410, HL085251, HL068986]; National Institute
of Neurological Disorders and Stroke (NINDS); National Institute on
Aging (NIA) [R01AG023629]; National Center for Advancing Translational
Sciences; CTSI [UL1TR000124]; National Institute of Diabetes and
Digestive and Kidney Disease Diabetes Research Center (DRC) [DK063491];
National Heart, Lung and Blood Institute [N01-HC-25195,
HHSN268201500001I]; Robert Dawson Evans Endowment of the Department of
Medicine at Boston University School of Medicine and Boston Medical
Center; NIH Heart, Lung and Blood Institute [5 R01 HL-63082]; NIA
[N01AG62101, N01AG62103, N01AG62106, 1R01AG032098-01A1]; Intramural
Research Program of the NIH, National Institute on Aging; National
Heart, Lung, and Blood Institute on Minority Health and Health
Disparities [HSN268201300046C, HHSN268201300047C, HHSN268201300048C,
HHSN268201300049C, HHSN268201300050C]; National Heart, Lung, and Blood
Institute (NHLBI) [N01 HC-95159, N01-HC-95160, N01-HC-95161,
N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166,
N01-HC-95167, N01-HC-95168, N01-HC-95169, RR-024156]; Bristol-Myers
Squibb; Netherlands Heart Foundation [2001 D 032]; European commission
[223004]; Netherlands Genomics Initiative (Netherlands Consortium for
Healthy Aging) [050-060-810]; Erasmus Medical Center; Erasmus University
Rotterdam; Netherlands Organization for Scientific Research; Netherlands
Organization for Health Research and Development (ZonMw); Research
Institute for Diseases; Netherlands Heart Foundation; Ministry of
Education, Culture and Science; Ministry of Health Welfare and Sports;
European Commission; Municipality of Rotterdam; Netherlands Organization
for Scientific Research (NWO) [175.010.2005.011, 911.03.012];
Netherlands Genomics Initiative (NGI)/Netherlands Organization for
Scientific Research (NWO) [050-060-810]
FX The funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript. AGES: This study
has been funded by National Institutes of Health (NIH) contract
N01-AG-1-2100, the National Institutes on Aging (NIA) Intramural
Research Program, Hjartavernd (the Icelandic Heart Association), and the
Althingi (the Icelandic Parliament). The study is approved by the
Icelandic National Bioethics Committee, VSN: 00-063. The researchers are
indebted to the participants for their willingness to participate in the
study. ARIC: 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),
R01HL087641, R01HL59367 and R01HL086694; National Human Genome Research
Institute contract U01HG004402; and National Institutes of Health
contract HHSN268200625226C. The authors thank the staff and participants
of the ARIC study for their important contributions. Infrastructure was
partly supported by Grant Number UL1RR025005, a component of the
National Institutes of Health and NIH Roadmap for Medical Research. CHS:
This CHS research was supported by NHLBI contracts HHSN268201200036C,
HHSN268200800007C, N01HC55222, N01HC85079, N01HC85080, N01HC85081,
N01HC85082, N01HC85083, N01HC85086; and NHLBI grants U01HL080295,
R01HL087652, R01HL105756, R01HL103612, and R01HL120393 with additional
contribution from the National Institute of Neurological Disorders and
Stroke (NINDS). Additional support was provided through R01AG023629 from
the National Institute on Aging (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. The content is solely the
responsibility of the authors and does not necessarily represent the
official views of the National Institutes of Health. FHS: This research
was conducted in part using data and resources from the Framingham Heart
Study of the National Heart Lung and Blood Institute of the National
Institutes of Health and Boston University School of Medicine. The
analyses reflect intellectual input and resource development from the
Framingham Heart Study investigators participating in the SNP Health
Association Resource (SHARe) project. This work was partially supported
by the National Heart, Lung and Blood Institute's Framingham Heart Study
(Contract No. N01-HC-25195 and HHSN268201500001I) and an NHLBI contract
with Affymetrix, Inc for genotyping services (Contract No.
N02-HL-6-4278). A portion of this research utilized the Linux Cluster
for Genetic Analysis (LinGA-II) funded by the Robert Dawson Evans
Endowment of the Department of Medicine at Boston University School of
Medicine and Boston Medical Center. Additional support for these
analyses was provided by R01HL103612 (PI Psaty, subcontract PI, Vasan).
GenHAT: This work was supported by NIH Heart, Lung and Blood Institute
grant 5 R01 HL-63082, Genetics of Hypertension Associated Treatment. The
ALLHAT study was supported by a contract with the National Heart, Lung
and Blood Institute.; Health ABC: The Health ABC study was supported by
NIA contracts N01AG62101, N01AG62103, and N01AG62106. The genome-wide
association study was funded by NIA grant 1R01AG032098-01A1 to Wake
Forest University Health Sciences and genotyping services were provided
by the Center for Inherited Disease Research (CIDR). CIDR is fully
funded through a federal contract from the National Institutes of Health
to The Johns Hopkins University, contract number HHSN268200782096C. This
research was supported in part by the Intramural Research Program of the
NIH, National Institute on Aging. HVH: The Heart and Vascular Health
Study research reported in this article were supported by National
Heart, Lung, and Blood Institute grants NHLBI grants, HL085251,
HL073410, HL085251, and HL068986. JHS: The authors thank the Jackson
Heart Study team (University of Mississippi Medical Center, Jackson
State University and Tougaloo College) and participants for their
long-term commitment that continues to improve our understanding of the
risk factors of cardiovascular diseases. The Jackson Heart Study is
supported by contracts HSN268201300046C, HHSN268201300047C,
HHSN268201300048C, HHSN268201300049C, HHSN268201300050C from the
National Heart, Lung, and Blood Institute on Minority Health and Health
Disparities. MESA: MESA and MESA SNP Health Association Resource (SHARe)
are conducted and supported by the National Heart, Lung, and Blood
Institute (NHLBI) in collaboration with MESA investigators. Support is
provided by grants and contracts N01 HC-95159, N01-HC-95160,
N01-HC-95161, N01-HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165,
N01-HC-95166, N01-HC-95167, N01-HC-95168, N01-HC-95169 and RR-024156.
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. The authors thank the other
investigators, the staff, and the participants of the MESA study for
their valuable contributions. A full list of participating MESA
investigators and institutions can be found at
http://www.mesa-nhlbi.org. PROSPER: The PROSPER study was supported by
an investigator initiated grant obtained from Bristol-Myers Squibb.
Prof. Dr. J. W. Jukema is an Established Clinical Investigator of the
Netherlands Heart Foundation (grant 2001 D 032). Support for genotyping
was provided by the seventh framework program of the European commission
(grant 223004) and by the Netherlands Genomics Initiative (Netherlands
Consortium for Healthy Aging grant 050-060-810). Rotterdam Study (RS):
The RS is supported by the Erasmus Medical Center and Erasmus University
Rotterdam; The Netherlands Organization for Scientific Research; The
Netherlands Organization for Health Research and Development (ZonMw);
the Research Institute for Diseases in the Elderly; The Netherlands
Heart Foundation; the Ministry of Education, Culture and Science; the
Ministry of Health Welfare and Sports; the European Commission; and the
Municipality of Rotterdam. Support for genotyping was provided by The
Netherlands Organization for Scientific Research (NWO)
(175.010.2005.011, 911.03.012) and Research Institute for Diseases in
the Elderly (RIDE). This study was supported by The Netherlands Genomics
Initiative (NGI)/Netherlands Organization for Scientific Research (NWO)
project nr. 050-060-810.
NR 31
TC 3
Z9 3
U1 0
U2 5
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD OCT 30
PY 2015
VL 10
IS 10
AR e0140496
DI 10.1371/journal.pone.0140496
PG 13
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CV0EH
UT WOS:000363920800007
PM 26516778
ER
PT J
AU McCormick, DL
Horn, TL
Johnson, WD
Peng, XJ
Lubet, RA
Steele, VE
AF McCormick, David L.
Horn, Thomas L.
Johnson, William D.
Peng, Xinjian
Lubet, Ronald A.
Steele, Vernon E.
TI Suppression of Rat Oral Carcinogenesis by Agonists of Peroxisome
Proliferator Activated Receptor gamma
SO PLOS ONE
LA English
DT Article
ID CANCER EPIDEMIOLOGY CONSORTIUM; PPAR-GAMMA; HUMAN-PAPILLOMAVIRUS;
INTERNATIONAL HEAD; POOLED ANALYSIS; RISK; ROSIGLITAZONE; EXPRESSION;
ALCOHOL; SMOKING
AB Peroxisome-proliferator-activated receptor. (PPAR.) is a ligand-activated transcription factor that regulates cell proliferation, differentiation, and apoptosis. In vivo studies were performed to evaluate the activities of two thiazolidinedione PPAR. agonists, rosiglitazone and pioglitazone, as inhibitors of oral carcinogenesis in rats. Oral squamous cell carcinomas (OSCC) were induced in male F344 rats by 4-nitroquinoline-1-oxide (NQO; 20 ppm in the drinking water for 10 weeks). In each study, groups of 30 NQO-treated rats were exposed to a PPAR. agonist beginning at week 10 (one day after completion of NQO administration) or at week 17 (7 weeks post-NQO); chemopreventive agent exposure was continued until study termination at week 22 (rosiglitazone study) or week 24 (pioglitazone study). Administration of rosiglitazone (800 mg/kg diet) beginning at week 10 increased survival, reduced oral cancer incidence, and reduced oral cancer invasion score in comparison to dietary controls; however, chemopreventive activity was largely lost when rosiglitazone administration was delayed until week 17. Administration of pioglitazone (500 mg/kg diet beginning at week 10 or 1000 mg/kg diet beginning at week 17) induced significant reductions in oral cancer incidence without significant effects on OSCC invasion scores. Transcript levels of PPAR. and its three transcriptional variants (PPAR.v1, PPAR.v2, and PPAR.v3) were not significantly different in OSCC versus age-and site-matched phenotypically normal oral tissues from rats treated with NQO. These data suggest that PPAR. provides a useful molecular target for oral cancer chemoprevention, and that overexpression of PPAR. at the transcriptional level in neoplastic lesions is not essential for chemopreventive efficacy.
C1 [McCormick, David L.; Horn, Thomas L.; Johnson, William D.; Peng, Xinjian] IIT Res Inst, Life Sci Grp, Chicago, IL 60616 USA.
[Lubet, Ronald A.; Steele, Vernon E.] NCI, Chemoprevent Agent Dev Res Grp, Canc Prevent Div, Bethesda, MD 20852 USA.
RP McCormick, DL (reprint author), IIT Res Inst, Life Sci Grp, Chicago, IL 60616 USA.
EM dmccormick@iitri.org
FU U.S. National Cancer Institute [N01-CN-85175, HHSN261200433003C
(N01-CN-43303)]
FX Grants N01-CN-85175 and HHSN261200433003C (N01-CN-43303) were awarded to
DLM by the U.S. National Cancer Institute (www.nci.nih.gov). National
Cancer Institute scientists (RAL and VES) participated in study design
and preparation of the manuscript.
NR 40
TC 2
Z9 2
U1 1
U2 2
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD OCT 30
PY 2015
VL 10
IS 10
AR e0141849
DI 10.1371/journal.pone.0141849
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CV0EH
UT WOS:000363920800087
PM 26516762
ER
PT J
AU Prince, TL
Kijima, T
Tatokoro, M
Lee, S
Tsutsumi, S
Yim, K
Rivas, C
Alarcon, S
Schwartz, H
Khamit-Kush, K
Scroggins, BT
Beebe, K
Trepel, JB
Neckers, L
AF Prince, Thomas L.
Kijima, Toshiki
Tatokoro, Manabu
Lee, Sunmin
Tsutsumi, Shinji
Yim, Kendrick
Rivas, Candy
Alarcon, Sylvia
Schwartz, Harvey
Khamit-Kush, Kofi
Scroggins, Bradley T.
Beebe, Kristin
Trepel, Jane B.
Neckers, Len
TI Client Proteins and Small Molecule Inhibitors Display Distinct Binding
Preferences for Constitutive and Stress-Induced HSP90 Isoforms and Their
Conformationally Restricted Mutants
SO PLOS ONE
LA English
DT Article
ID HEAT-SHOCK PROTEINS; IN-VIVO; ATP HYDROLYSIS; TRANSCRIPTION FACTOR;
CHAPERONE MACHINERY; COMPLEX; GELDANAMYCIN; CELLS; ACTIVATION; MECHANISM
AB The two cytosolic/nuclear isoforms of the molecular chaperone HSP90, stress-inducible HSP90 alpha and constitutively expressed HSP90 beta, fold, assemble and maintain the three-dimensional structure of numerous client proteins. Because many HSP90 clients are important in cancer, several HSP90 inhibitors have been evaluated in the clinic. However, little is known concerning possible unique isoform or conformational preferences of either individual HSP90 clients or inhibitors. In this report, we compare the relative interaction strength of both HSP90 alpha and HSP90 beta with the transcription factors HSF1 and HIF1 alpha, the kinases ERBB2 and MET, the E3-ubiquitin ligases KEAP1 and RHOBTB2, and the HSP90 inhibitors geldanamycin and ganetespib. We observed unexpected differences in relative client and drug preferences for the two HSP90 isoforms, with HSP90 alpha binding each client protein with greater apparent affinity compared to HSP90 beta, while HSP90 beta bound each inhibitor with greater relative interaction strength compared to HSP90 alpha. Stable HSP90 interaction was associated with reduced client activity. Using a defined set of HSP90 conformational mutants, we found that some clients interact strongly with a single, ATP-stabilized HSP90 conformation, only transiently populated during the dynamic HSP90 chaperone cycle, while other clients interact equally with multiple HSP90 conformations. These data suggest different functional requirements among HSP90 clientele that, for some clients, are likely to be ATP-independent. Lastly, the two inhibitors examined, although sharing the same binding site, were differentially able to access distinct HSP90 conformational states.
C1 [Prince, Thomas L.; Kijima, Toshiki; Tatokoro, Manabu; Tsutsumi, Shinji; Yim, Kendrick; Rivas, Candy; Schwartz, Harvey; Khamit-Kush, Kofi; Beebe, Kristin; Neckers, Len] NCI, Urol Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Lee, Sunmin; Alarcon, Sylvia; Trepel, Jane B.] NCI, Dev Therapeut Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Scroggins, Bradley T.] NCI, Radiat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Prince, TL (reprint author), NCI, Urol Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM thomas.prince@nih.gov; neckers@nih.gov
FU Intramural Research Program, NCI [Z01 BC011032-01, Z01 SC010074-12];
JSPS Research Fellowship for Japanese Biomedical and Behavioral
Researchers at NIH
FX This work was supported by funds to L.N. from the Intramural Research
Program, NCI (project #s Z01 BC011032-01 and Z01 SC010074-12).
Biotinylated ganetespib (STA-7346) was provided by Weiwen Ying (Synta
Pharmaceuticals, Lexington, MA). T.K. is supported by a JSPS Research
Fellowship for Japanese Biomedical and Behavioral Researchers at NIH.
NR 55
TC 4
Z9 4
U1 0
U2 2
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD OCT 30
PY 2015
VL 10
IS 10
AR e0141786
DI 10.1371/journal.pone.0141786
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CV0EH
UT WOS:000363920800077
PM 26517842
ER
PT J
AU Bodelon, C
Heaphy, CM
Meeker, AK
Geller, B
Vacek, PM
Weaver, DL
Chicoine, RE
Shepherd, JA
Mahmoudzadeh, AP
Patel, DA
Brinton, LA
Sherman, ME
Gierach, GL
AF Bodelon, Clara
Heaphy, Christopher M.
Meeker, Alan K.
Geller, Berta
Vacek, Pamela M.
Weaver, Donald L.
Chicoine, Rachael E.
Shepherd, John A.
Mahmoudzadeh, Amir Pasha
Patel, Deesha A.
Brinton, Louise A.
Sherman, Mark E.
Gierach, Gretchen L.
TI Leukocyte telomere length and its association with mammographic density
and proliferative diagnosis among women undergoing diagnostic
image-guided breast biopsy
SO BMC CANCER
LA English
DT Article
DE Telomere; Mammographic density; Breast pathology; Hyperplasia; Breast
diseases; Breast neoplasms
ID CANCER RISK; SHORTENING OCCURS; PATERNAL AGE; BLOOD-CELLS; METAANALYSIS;
HORMONES; HEALTH; EPITHELIUM; MENOPAUSE; OBESITY
AB Background: Elevated mammographic density (MD) is a strong breast cancer risk factor but the mechanisms underlying the association are poorly understood. High MD and breast cancer risk may reflect cumulative exposures to factors that promote epithelial cell division. One marker of cellular replicative history is telomere length, but its association with MD is unknown. We investigated the relation of telomere length, a marker of cellular replicative history, with MD and biopsy diagnosis.
Methods: One hundred and ninety-five women, ages 40-65, were clinically referred for image-guided breast biopsies at an academic facility in Vermont. Relative peripheral blood leukocyte telomere length (LTL) was measured using quantitative polymerase chain reaction. MD volume was quantified in cranio-caudal views of the breast contralateral to the primary diagnosis in digital mammograms using a breast density phantom, while MD area (cm(2)) was measured using thresholding software. Associations between log-transformed LTL and continuous MD measurements (volume and area) were evaluated using linear regression models adjusted for age and body mass index. Analyses were stratified by biopsy diagnosis: proliferative (hyperplasia, in-situ or invasive carcinoma) or non-proliferative (benign or other non-proliferative benign diagnoses).
Results: Mean relative LTL in women with proliferative disease (n = 141) was 1.6 (SD = 0.9) vs. 1.2 (SD = 0.6) in those with non-proliferative diagnoses (n = 54) (P = 0.002). Mean percent MD volume did not differ by diagnosis (P = 0.69). LTL was not associated with MD in women with proliferative (P = 0.89) or non-proliferative (P = 0.48) diagnoses. However, LTL was associated with a significant increased risk of proliferative diagnosis (adjusted OR = 2.46, 95 % CI: 1.47, 4.42).
Conclusions: Our analysis of LTL did not find an association with MD. However, our findings suggest that LTL may be a marker of risk for proliferative pathology among women referred for biopsy based on breast imaging.
C1 [Heaphy, Christopher M.; Meeker, Alan K.] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD USA.
[Meeker, Alan K.] Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD USA.
[Meeker, Alan K.] Johns Hopkins Univ, Sch Med, Dept Urol, Baltimore, MD USA.
[Geller, Berta] Univ Vermont, Coll Med, Dept Hlth Promot Res, Burlington, VT USA.
[Geller, Berta; Vacek, Pamela M.; Weaver, Donald L.; Chicoine, Rachael E.] Vermont Canc Ctr, Burlington, VT USA.
[Vacek, Pamela M.] Univ Vermont, Coll Med, Dept Biostat, Burlington, VT USA.
[Weaver, Donald L.] Univ Vermont, Coll Med, Dept Pathol, Burlington, VT USA.
[Chicoine, Rachael E.] Univ Vermont, Coll Med, Off Hlth Promot Res, Burlington, VT USA.
[Shepherd, John A.; Mahmoudzadeh, Amir Pasha] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94143 USA.
[Sherman, Mark E.] Natl Canc Inst, Breast & Gynecol Canc Res Grp, Canc Prevent Div, Rockville, MD USA.
[Bodelon, Clara] Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
EM clara.bodelon@nih.gov
RI Gierach, Gretchen/E-1817-2016
OI Gierach, Gretchen/0000-0002-0165-5522
FU National Center for Research Resources - blood processing at the
University of Vermont's General Clinical Research Center [M01 RR000109];
Intramural Research Program of the Division of Cancer Epidemiology and
Genetics of the National Cancer Institute; National Cancer Institute
federal funds [HHSN261200800001E]; National Cancer Institute
[U01CA70013, 1R21CA157254]
FX This study was supported by the Intramural Research Program of the
Division of Cancer Epidemiology and Genetics of the National Cancer
Institute and National Cancer Institute federal funds awarded under
Contract No. HHSN261200800001E to SAIC-Frederick, Inc. Breast Cancer
Research Stamp Funds and cooperative agreement U01CA70013 (B. Geller, P.
Vacek, D. Weaver, R. Chicoine) and 1R21CA157254 (J. Shepherd, A.
Mahmoudzadeh) from the National Cancer Institute funded some of the data
collection and image analysis for this study. Grant number M01 RR000109
from the National Center for Research Resources funded the blood
processing at the University of Vermont's General Clinical Research
Center. The content of this publication does not necessarily reflect the
views or policies of the Department of Health and Human Services, nor
does mention of trade names, commercial products, or organizations imply
endorsement by the U.S. Government. The authors are indebted to the
participants in the BREAST Stamp Project for their outstanding
cooperation and to the physicians, pathologists, nurses, technologists,
and interviewers for their efforts in the field. The authors thank Clair
Bove, Patricia Lutton, Ellen Young, Aileen Burke, Laura Linville, Daphne
Papathomas, and Jeff Wang for research assistance. We also thank Bo Fan
from the University of California at San Francisco for providing the
area measures of mammographic density, Bharathi Anekella from SeraCare
Life Sciences for assistance with DNA extraction, Sally Larson from the
Cancer Genomics Research Laboratory for assistance with DNA
quantitation, Janet Lawler-Heaver and Kerry Grace Morrissey from Westat
for study management support, and Franklin Demuth at Information
Management Services for data support and analysis.
NR 50
TC 1
Z9 1
U1 1
U2 7
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2407
J9 BMC CANCER
JI BMC Cancer
PD OCT 30
PY 2015
VL 15
AR 823
DI 10.1186/s12885-015-1860-2
PG 12
WC Oncology
SC Oncology
GA CU9BD
UT WOS:000363836900004
PM 26519084
ER
PT J
AU Xi, S
Inchauste, S
Guo, H
Shan, J
Xiao, Z
Xu, H
Miettenen, M
Zhang, MR
Hong, JA
Raiji, MT
Altorki, NK
Casson, AG
Beer, DG
Robles, AI
Bowman, ED
Harris, CC
Steinberg, SM
Schrump, DS
AF Xi, S.
Inchauste, S.
Guo, H.
Shan, J.
Xiao, Z.
Xu, H.
Miettenen, M.
Zhang, M. R.
Hong, J. A.
Raiji, M. T.
Altorki, N. K.
Casson, A. G.
Beer, D. G.
Robles, A. I.
Bowman, E. D.
Harris, C. C.
Steinberg, S. M.
Schrump, D. S.
TI Cigarette smoke mediates epigenetic repression of miR-217 during
esophageal adenocarcinogenesis
SO ONCOGENE
LA English
DT Article
ID PANCREATIC DUCTAL ADENOCARCINOMA; SQUAMOUS-CELL CARCINOMA; LINEAGE
PROGRESSION; MICRORNA EXPRESSION; BARRETTS-ESOPHAGUS; CANCER CELLS;
E-CADHERIN; CARCINOGENESIS; INVASION; OVEREXPRESSION
AB Although microRNAs (miRs) have been implicated in the pathogenesis of various human malignancies, limited information is available regarding mechanisms by which these noncoding RNAs contribute to initiation and progression of tobacco-induced esophageal cancers. In this study, array and quantitative reverse transcriptase-PCR techniques were used to examine miR expression in immortalized esophageal epithelia (IEE) and esophageal adenocarcinoma (EAC) cells cultured in normal media with or without cigarette smoke condensate (CSC). Under relevant exposure conditions, CSC significantly decreased miR-217 expression in these cells. Endogenous levels of miR-217 expression in cultured EAC cells (EACC)/primary EACs were significantly lower than those observed in IEE/paired normal esophageal tissues. RNA crosslink immunoprecipitation, quantitative reverse transcriptase-PCR (qRT-PCR) and immunoblot experiments demonstrated direct interaction of miR-217 with kallikrein 7 (KLK7), encoding a putative oncogene not previously implicated in EAC. Repression of miR-217 correlated with increased levels of KLK7 in primary EACs, particularly those from smokers. Chromatin and methylated DNA immunoprecipitation experiments demonstrated that CSC-mediated repression of miR-217 coincided with DNMT3b-dependent hypermethylation and decreased occupancy of nuclear factor 1 within the miR-217 genomic locus. Deoxyazacytidine induced miR-217 expression and downregulated KLK7 in EACC; deoxyazacytidine also attenuated CSC-mediated miR-217 repression and upregulation of KLK7 in IEE and EACC. Overexpression of miR-217 significantly decreased, whereas overexpression of KLK7 increased proliferation, invasion and tumorigenicity of EACC. Collectively, these data demonstrate that epigenetic repression of miR-217 contributes to the pathogenesis of EAC via upregulation of KLK7 and suggest that restoration of miR-217 expression may be a novel treatment strategy for these malignancies.
C1 [Xi, S.; Inchauste, S.; Zhang, M. R.; Hong, J. A.; Raiji, M. T.; Schrump, D. S.] NCI, Thorac Surg Sect, Thorac & GI Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Guo, H.] Shandong Tumor Hosp & Inst, Gastrointestinal Surg, Jinan, Shandong, Peoples R China.
[Shan, J.] NCI, Adv Biomed Comp Ctr, SAIC Frederick, Frederick, MD 21701 USA.
[Xiao, Z.] NCI, Canc & Inflammat Lab, Frederick, MD 21701 USA.
[Xu, H.] NCI, Lab Canc Prevent, Frederick, MD 21701 USA.
[Miettenen, M.] NCI, Pathol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Altorki, N. K.] Weill Cornell Univ, Med Ctr, Dept Thorac Surg, New York, NY USA.
[Casson, A. G.] Univ Saskatchewan, Dept Surg, Saskatoon, SK, Canada.
[Beer, D. G.] Univ Michigan, Sect Thorac Surg, Ann Arbor, MI 48109 USA.
[Robles, A. I.; Bowman, E. D.; Harris, C. C.] NCI, Lab Human Carcinogenesis, Ctr Canc Res, Bethesda, MD 20892 USA.
[Steinberg, S. M.] NCI, Biostat & Data Management Sect, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Schrump, DS (reprint author), NCI, Thorac Surg Sect, Thorac & GI Oncol Branch, Ctr Canc Res, Bldg 10,Room 4-3942,10 Ctr Dr, Bethesda, MD 20892 USA.
EM David_Schrump@nih.gov
FU NIH intramural funding; Stephen J. Solarz Memorial Fund
FX We thank Ms Jan Pappas for assistance with manuscript preparation. This
study was supported by NIH intramural funding and the Stephen J. Solarz
Memorial Fund.
NR 43
TC 4
Z9 4
U1 1
U2 5
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0950-9232
EI 1476-5594
J9 ONCOGENE
JI Oncogene
PD OCT 29
PY 2015
VL 34
IS 44
BP 5548
EP 5559
DI 10.1038/onc.2015.10
PG 12
WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics &
Heredity
GA CV9FX
UT WOS:000364594000004
PM 25703328
ER
PT J
AU Krupovic, M
Cvirkaite-Krupovic, V
Prangishvili, D
Koonin, EV
AF Krupovic, Mart
Cvirkaite-Krupovic, Virginija
Prangishvili, David
Koonin, Eugene V.
TI Evolution of an archaeal virus nucleocapsid protein from the
CRISPR-associated Cas4 nuclease
SO BIOLOGY DIRECT
LA English
DT Article
DE Virus evolution; Capsid proteins; Nucleocapsid; Virus origin; Archaea
viruses
ID STRANDED DNA VIRUSES; THERMOPROTEUS-TENAX; ADAPTIVE IMMUNITY; VIRAL
UNIVERSE; SYSTEMS; TTV1; CLASSIFICATION; TRANSPOSONS; UNIFICATION;
POLYMERASE
AB Many proteins of viruses infecting hyperthermophilic Crenarchaeota have no detectable homologs in current databases, hampering our understanding of viral evolution. We used sensitive database search methods and structural modeling to show that a nucleocapsid protein (TP1) of Thermoproteus tenax virus 1 (TTV1) is a derivative of the Cas4 nuclease, a component of the CRISPR-Cas adaptive immunity system that is encoded also by several archaeal viruses. In TTV1, the Cas4 gene was split into two, with the N-terminal portion becoming TP1, and lost some of the catalytic amino acid residues, apparently resulting in the inactivation of the nuclease. To our knowledge, this is the first described case of exaptation of an enzyme for a virus capsid protein function.
C1 [Krupovic, Mart; Cvirkaite-Krupovic, Virginija; Prangishvili, David] Inst Pasteur, Dept Microbiol, Unite Biol Mol Gene Chez Extremophiles, F-75015 Paris, France.
[Koonin, Eugene V.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
RP Krupovic, M (reprint author), Inst Pasteur, Dept Microbiol, Unite Biol Mol Gene Chez Extremophiles, F-75015 Paris, France.
EM krupovic@pasteur.fr
RI Krupovic, Mart/I-4209-2012
OI Krupovic, Mart/0000-0001-5486-0098
FU Agence nationale de la recherche (ANR) program BLANC, project EXAVIR; US
Department of Health and Human Services
FX This work was supported by the Agence nationale de la recherche (ANR)
program BLANC, project EXAVIR. EVK is supported by intramural funds of
the US Department of Health and Human Services (to the National Library
of Medicine).
NR 40
TC 3
Z9 3
U1 3
U2 16
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1745-6150
J9 BIOL DIRECT
JI Biol. Direct
PD OCT 29
PY 2015
VL 10
AR 65
DI 10.1186/s13062-015-0093-2
PG 6
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA CV1GQ
UT WOS:000364002100001
PM 26514828
ER
PT J
AU Kliment, CR
Araki, T
Doyle, TJ
Gao, W
Dupuis, J
Latourelle, JC
Zazueta, OE
Fernandez, IE
Nishino, M
Okajima, Y
Ross, JC
Estepar, RSJ
Diaz, AA
Lederer, DJ
Schwartz, DA
Silverman, EK
Rosas, IO
Washko, GR
O'Connor, GT
Hatabu, H
Hunninghake, GM
AF Kliment, Corrine R.
Araki, Tetsuro
Doyle, Tracy J.
Gao, Wei
Dupuis, Josee
Latourelle, Jeanne C.
Zazueta, Oscar E.
Fernandez, Isis E.
Nishino, Mizuki
Okajima, Yuka
Ross, James C.
Estepar, Raul San Jose
Diaz, Alejandro A.
Lederer, David J.
Schwartz, David A.
Silverman, Edwin K.
Rosas, Ivan O.
Washko, George R.
O'Connor, George T.
Hatabu, Hiroto
Hunninghake, Gary M.
TI A comparison of visual and quantitative methods to identify interstitial
lung abnormalities
SO BMC PULMONARY MEDICINE
LA English
DT Article
DE High attenuation areas; Idiopathic pulmonary fibrosis; Interstitial lung
disease; Interstitial lung abnormalities (ILA); MUC5B
ID IDIOPATHIC PULMONARY-FIBROSIS; MUC5B PROMOTER POLYMORPHISM; GENOME-WIDE
ASSOCIATION; AUTOMATED QUANTIFICATION; CT METRICS; DISEASE; EMPHYSEMA;
SYSTEM; SUSCEPTIBILITY; DIAGNOSIS
AB Background: Evidence suggests that individuals with interstitial lung abnormalities (ILA) on a chest computed tomogram (CT) may have an increased risk to develop a clinically significant interstitial lung disease (ILD). Although methods used to identify individuals with ILA on chest CT have included both automated quantitative and qualitative visual inspection methods, there has been not direct comparison between these two methods. To investigate this relationship, we created lung density metrics and compared these to visual assessments of ILA.
Methods: To provide a comparison between ILA detection methods based on visual assessment we generated measures of high attenuation areas (HAAs, defined by attenuation values between -600 and -250 Hounsfield Units) in >4500 participants from both the COPDGene and Framingham Heart studies (FHS). Linear and logistic regressions were used for analyses.
Results: Increased measures of HAAs (in >= 10 % of the lung) were significantly associated with ILA defined by visual inspection in both cohorts (P < 0.0001); however, the positive predictive values were not very high (19 % in COPDGene and 13 % in the FHS). In COPDGene, the association between HAAs and ILA defined by visual assessment were modified by the percentage of emphysema and body mass index. Although increased HAAs were associated with reductions in total lung capacity in both cohorts, there was no evidence for an association between measurement of HAAs and MUC5B promoter genotype in the FHS.
Conclusion: Our findings demonstrate that increased measures of lung density may be helpful in determining the severity of lung volume reduction, but alone, are not strongly predictive of ILA defined by visual assessment. Moreover, HAAs were not associated with MUC5B promoter genotype.
C1 [Kliment, Corrine R.; Doyle, Tracy J.; Zazueta, Oscar E.; Fernandez, Isis E.; Diaz, Alejandro A.; Silverman, Edwin K.; Rosas, Ivan O.; Washko, George R.; Hunninghake, Gary M.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Pulm & Crit Care Div, Boston, MA 02115 USA.
[Araki, Tetsuro; Nishino, Mizuki; Okajima, Yuka; Hatabu, Hiroto] Brigham & Womens Hosp, Dept Radiol, Boston, MA 02115 USA.
[Gao, Wei; Dupuis, Josee] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Dupuis, Josee; O'Connor, George T.] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Latourelle, Jeanne C.] Boston Univ, Dept Med, Boston, MA 02215 USA.
[Latourelle, Jeanne C.] Boston Univ, Dept Neurol, Boston, MA 02215 USA.
[Nishino, Mizuki; Estepar, Raul San Jose; Washko, George R.; Hatabu, Hiroto; Hunninghake, Gary M.] Brigham & Womens Hosp, Ctr Pulm Funct Imaging, Boston, MA 02115 USA.
[Ross, James C.; Silverman, Edwin K.] Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA.
[Ross, James C.; Estepar, Raul San Jose] Brigham & Womens Hosp, Dept Radiol, Surg Planning Lab, Boston, MA 02115 USA.
[Diaz, Alejandro A.] Pontificia Univ Catolica Chile, Dept Pulm Dis, Santiago, Chile.
[Lederer, David J.] Columbia Univ, Coll Phys & Surg, Div Pulm & Crit Care, New York, NY USA.
[Lederer, David J.] Columbia Univ, Dept Epidemiol, Mailman Sch Publ Hlth, New York, NY USA.
[Schwartz, David A.] Univ Colorado, Dept Med, Denver, CO USA.
[O'Connor, George T.] Boston Univ, Sch Med, Dept Med, Ctr Pulm, Boston, MA 02118 USA.
RP Hunninghake, GM (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Pulm & Crit Care Div, Boston, MA 02115 USA.
EM ghunninghake@partners.org
FU NIH [K23 CA157631, K25 HL104085, R01 HL116931, R01 HL116473, R01
HL103676, R01 HL114626, R01 HL089856, P01 HL105339, P01 HL114501, U01
HL105371, R01 HL107246, R01 HL111024]; National Heart, Lung and Blood
Institute [R01-HL095393, R01-HL097163, P01-HL092870, RC2-HL101715];
Veterans Administration [1I01BX001534]; NHLBI's Framingham Heart Study
[N01-HC-25195]; [R01 HL089897]
FX Dr. Nishino is supported by NIH Grant Number: K23 CA157631. Dr. San Jose
Estepar is supported by NIH Grant Numbers: K25 HL104085, R01 HL116931
and R01 HL116473. Dr. Lederer is supported by NIH Grant Numbers: R01
HL103676 and R01 HL114626. Dr. Schwartz is supported by the National
Heart, Lung and Blood Institute (R01-HL095393, R01-HL097163,
P01-HL092870, and RC2-HL101715) and the Veterans Administration
(1I01BX001534). Dr. Silverman is supported by NIH Grant Numbers: R01
HL089856, P01 HL105339, and P01 HL114501. Dr. Rosas is supported by NIH
Grant Number: U01 HL105371 and P01 HL114501. Dr. Washko is supported by
NIH Grant Number: R01 HL116473, R01 HL107246 and P01 HL114501. Dr.
Hunninghake is supported by NIH Grant Number: U01 HL105371, P01
HL114501, and R01 HL111024. This work was partially supported by the
NHLBI's Framingham Heart Study contract: N01-HC-25195 (FHS) and by R01
HL089897 and R01 HL089856 (COPDGene) and R01 HL111024. This paper is
subject to the NIH public access policy: http://publicaccess.nih.gov.
NR 35
TC 2
Z9 2
U1 2
U2 4
PU BIOMED CENTRAL LTD
PI LONDON
PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
SN 1471-2466
J9 BMC PULM MED
JI BMC Pulm. Med.
PD OCT 29
PY 2015
VL 15
AR 134
DI 10.1186/s12890-015-0124-x
PG 9
WC Respiratory System
SC Respiratory System
GA CU7RP
UT WOS:000363739400001
PM 26514822
ER
PT J
AU Polackwich, RJ
Koch, D
McAllister, R
Geller, HM
Urbach, JS
AF Polackwich, Robert J.
Koch, Daniel
McAllister, Ryan
Geller, Herbert M.
Urbach, Jeffrey S.
TI Traction force and tension fluctuations in growing axons
SO FRONTIERS IN CELLULAR NEUROSCIENCE
LA English
DT Article
DE growth cone; stress; mechanical; traction force; axon outgrowth; DRG
neurons
ID FOCAL ADHESIONS; MIGRATING CELLS; NEURONS; MICROSCOPY; GROWTH;
INHIBITION; MECHANICS; OUTGROWTH; DYNAMICS
AB Actively generated mechanical forces play a central role in axon growth and guidance, but the mechanisms that underly force generation and regulation in growing axons remain poorly understood. We report measurements of the dynamics of traction stresses from growth cones of actively advancing axons from postnatal rat DRG neurons. By tracking the movement of the growth cone and analyzing the traction stress field from a reference frame that moves with it, we are able to show that there is a clear and consistent average stress field that underlies the complex spatial stresses present at any one time. The average stress field has strong maxima on the sides of the growth cone, directed inward toward the growth cone neck. This pattern represents a contractile stress contained within the growth cone, and a net force that is balanced by the axon tension. Using high time-resolution measurements of the growth cone traction stresses, we show that the stress field is composed of fluctuating local stress peaks, with a large number peaks that live for a short time, a population of peaks whose lifetime distribution follows an exponential decay, and a small number of very long-lived peaks. We show that the high time-resolution data also reveal that the tension appears to vary randomly over short time scales, roughly consistent with the lifetime of the stress peaks, suggesting that the tension fluctuations originate from stochastic adhesion dynamics.
C1 [Polackwich, Robert J.; Koch, Daniel; McAllister, Ryan; Urbach, Jeffrey S.] Georgetown Univ, Dept Phys, Washington, DC 20057 USA.
[Polackwich, Robert J.; Koch, Daniel; McAllister, Ryan; Urbach, Jeffrey S.] Georgetown Univ, Inst Soft Matter Synth & Metrol, Washington, DC USA.
[Geller, Herbert M.] NHLBI, Dev Neurobiol Sect, Cell Biol & Physiol Ctr, NIH, Bethesda, MD 20892 USA.
RP Polackwich, RJ (reprint author), Georgetown Univ, Dept Phys, Washington, DC 20057 USA.
EM rjp73@georgetown.edu
OI Urbach, Jeffrey/0000-0002-1593-520X
FU National Institute of Neurological Disorders and Stroke
[1R01NS064250-01]; National Heart, Lung, and Blood Institute Intramural
Research Program
FX This work was supported by National Institute of Neurological Disorders
and Stroke grant 1R01NS064250-01 (JU) and the National Heart, Lung, and
Blood Institute Intramural Research Program (HG).
NR 29
TC 0
Z9 0
U1 5
U2 12
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015,
SWITZERLAND
SN 1662-5102
J9 FRONT CELL NEUROSCI
JI Front. Cell. Neurosci.
PD OCT 29
PY 2015
VL 9
AR 417
DI 10.3389/fncel.2015.00417
PG 9
WC Neurosciences
SC Neurosciences & Neurology
GA CU8PK
UT WOS:000363805000001
PM 26578882
ER
PT J
AU Peifer, M
Hertwig, F
Roels, F
Dreidax, D
Gartlgruber, M
Menon, R
Kramer, A
Roncaioli, JL
Sand, F
Heuckmann, JM
Ikram, F
Schmidt, R
Ackermann, S
Engesser, A
Kahlert, Y
Vogel, W
Altmuller, J
Nurnberg, P
Thierry-Mieg, J
Thierry-Mieg, D
Mariappan, A
Heynck, S
Mariotti, E
Henrich, KO
Gloeckner, C
Bosco, G
Leuschner, I
Schweiger, MR
Savelyeva, L
Watkins, SC
Shao, CX
Bell, E
Hofer, T
Achter, V
Lang, U
Theissen, J
Volland, R
Saadati, M
Eggert, A
de Wilde, B
Berthold, F
Peng, ZY
Zhao, C
Shi, LM
Ortmann, M
Buttner, R
Perner, S
Hero, B
Schramm, A
Schulte, JH
Herrmann, C
O'Sullivan, RJ
Westermann, F
Thomas, RK
Fischer, M
AF Peifer, Martin
Hertwig, Falk
Roels, Frederik
Dreidax, Daniel
Gartlgruber, Moritz
Menon, Roopika
Kraemer, Andrea
Roncaioli, Justin L.
Sand, Frederik
Heuckmann, Johannes M.
Ikram, Fakhera
Schmidt, Rene
Ackermann, Sandra
Engesser, Anne
Kahlert, Yvonne
Vogel, Wenzel
Altmueller, Janine
Nuernberg, Peter
Thierry-Mieg, Jean
Thierry-Mieg, Danielle
Mariappan, Aruljothi
Heynck, Stefanie
Mariotti, Erika
Henrich, Kai-Oliver
Gloeckner, Christian
Bosco, Graziella
Leuschner, Ivo
Schweiger, Michal R.
Savelyeva, Larissa
Watkins, Simon C.
Shao, Chunxuan
Bell, Emma
Hoefer, Thomas
Achter, Viktor
Lang, Ulrich
Theissen, Jessica
Volland, Ruth
Saadati, Maral
Eggert, Angelika
de Wilde, Bram
Berthold, Frank
Peng, Zhiyu
Zhao, Chen
Shi, Leming
Ortmann, Monika
Buettner, Reinhard
Perner, Sven
Hero, Barbara
Schramm, Alexander
Schulte, Johannes H.
Herrmann, Carl
O'Sullivan, Roderick J.
Westermann, Frank
Thomas, Roman K.
Fischer, Matthias
TI Telomerase activation by genomic rearrangements in high-risk
neuroblastoma
SO NATURE
LA English
DT Article
ID TERT PROMOTER MUTATIONS; GENE; LANDSCAPE; ENHANCERS; MELANOMA
AB Neuroblastoma is a malignant paediatric tumour of the sympathetic nervous system(1). Roughly half of these tumours regress spontaneously or are cured by limited therapy. By contrast, high-risk neuroblastomas have an unfavourable clinical course despite intensive multimodal treatment, and their molecular basis has remained largely elusive(2-4). Here we have performed whole-genome sequencing of 56 neuroblastomas (high-risk, n = 39; low-risk, n = 17) and discovered recurrent genomic rearrangements affecting a chromosomal region at 5p15.33 proximal of the telomerase reverse transcriptase gene (TERT). These rearrangements occurred only in high-risk neuroblastomas (12/39, 31%) in a mutually exclusive fashion with MYCN amplifications and ATRX mutations, which are known genetic events in this tumour type(1,2,5). In an extended case series (n = 217), TERT rearrangements defined a subgroup of high-risk tumours with particularly poor outcome. Despite a large structural diversity of these rearrangements, they all induced massive transcriptional upregulation of TERT. In the remaining high-risk tumours, TERT expression was also elevated in MYCN-amplified tumours, whereas alternative lengthening of telomeres was present in neuroblastomas without TERT or MYCN alterations, suggesting that telomere lengthening represents a central mechanism defining this subtype. The 5p15.33 rearrangements juxtapose the TERT coding sequence to strong enhancer elements, resulting in massive chromatin remodelling and DNA methylation of the affected region. Supporting a functional role of TERT, neuroblastoma cell lines bearing rearrangements or amplified MYCN exhibited both upregulated TERT expression and enzymatic telomerase activity. In summary, our findings show that remodelling of the genomic context abrogates transcriptional silencing of TERT in high-risk neuroblastoma and places telomerase activation in the centre of transformation in a large fraction of these tumours.
C1 [Peifer, Martin; Bosco, Graziella; Thomas, Roman K.] Univ Cologne, Ctr Integrated Oncol Cologne Bonn, Fac Med, Dept Translat Genom, D-50931 Cologne, Germany.
[Peifer, Martin; Hertwig, Falk; Roels, Frederik; Kraemer, Andrea; Sand, Frederik; Ikram, Fakhera; Ackermann, Sandra; Nuernberg, Peter; Mariappan, Aruljothi; Fischer, Matthias] Univ Cologne, Ctr Mol Med Cologne CMMC, D-50931 Cologne, Germany.
[Hertwig, Falk; Roels, Frederik; Kraemer, Andrea; Ikram, Fakhera; Ackermann, Sandra; Engesser, Anne; Kahlert, Yvonne; Theissen, Jessica; Volland, Ruth; Berthold, Frank; Hero, Barbara; Fischer, Matthias] Univ Cologne, Univ Childrens Hosp Cologne, Fac Med, Dept Pediat Oncol & Hematol, D-50937 Cologne, Germany.
[Dreidax, Daniel; Gartlgruber, Moritz; Henrich, Kai-Oliver; Savelyeva, Larissa; Bell, Emma; Westermann, Frank] German Canc Res Ctr, Div Neuroblastoma Genom B087, D-69120 Heidelberg, Germany.
[Menon, Roopika; Vogel, Wenzel; Perner, Sven] Univ Hosp Bonn, Ctr Integrated Oncol Cologne Bonn, Inst Pathol, Dept Prostate Canc Res, D-53127 Bonn, Germany.
[Menon, Roopika; Heuckmann, Johannes M.; Heynck, Stefanie; Mariotti, Erika; Gloeckner, Christian] NEO New Oncol AG, D-51105 Cologne, Germany.
[Roncaioli, Justin L.; O'Sullivan, Roderick J.] Univ Pittsburgh, Inst Canc, Hillman Canc Ctr, Dept Pharmacol & Chem Biol, Pittsburgh, PA 15213 USA.
[Ikram, Fakhera; Altmueller, Janine; Nuernberg, Peter] Univ Cologne, Cologne Ctr Genom, D-50931 Cologne, Germany.
[Schmidt, Rene] Univ Munster, Inst Biostat & Clin Res, D-48149 Munster, Germany.
[Nuernberg, Peter] Univ Cologne, Cologne Excellence Cluster Cellular Stress Respon, D-50931 Cologne, Germany.
[Thierry-Mieg, Jean; Thierry-Mieg, Danielle] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA.
[Leuschner, Ivo] Univ Kiel, Dept Pathol, D-24118 Kiel, Germany.
[Schweiger, Michal R.] Univ Cologne, Funct Epigen, D-50931 Cologne, Germany.
[Watkins, Simon C.] Univ Pittsburgh, Ctr Biol Imaging, Dept Cell Biol, Pittsburgh, PA 15261 USA.
[Shao, Chunxuan; Hoefer, Thomas] German Canc Res Ctr, Div Theoret Syst Biol, D-69120 Heidelberg, Germany.
[Achter, Viktor; Lang, Ulrich] Univ Cologne, Comp Ctr, D-50931 Cologne, Germany.
[Lang, Ulrich] Univ Cologne, Dept Informat, D-50931 Cologne, Germany.
[Saadati, Maral] German Canc Res Ctr, Div Biostat, D-69120 Heidelberg, Germany.
[Eggert, Angelika; Schulte, Johannes H.] Charite Univ Med Ctr Berlin, Dept Pediat Oncol & Hematol, D-10117 Berlin, Germany.
[de Wilde, Bram] Univ Ghent, Ctr Med Genet, B-9000 Ghent, Belgium.
[Peng, Zhiyu] BGI Shenzhen, Shenzhen 518083, Guangdong, Peoples R China.
[Zhao, Chen; Shi, Leming] Fudan Univ, Ctr Pharmacogen, State Key Lab Genet Engn, Shanghai 201203, Peoples R China.
[Zhao, Chen; Shi, Leming] Fudan Univ, Fudan Zhangjiang Ctr Clin Genom, State Key Lab Genet Engn, Shanghai 201203, Peoples R China.
[Zhao, Chen; Shi, Leming] Fudan Univ, Sch Pharm, MOE Key Lab Contemporary Anthropol, Shanghai 201203, Peoples R China.
[Zhao, Chen; Shi, Leming] Fudan Univ, Sch Life Sci, Shanghai 201203, Peoples R China.
[Ortmann, Monika; Buettner, Reinhard; Thomas, Roman K.] Univ Cologne, Dept Pathol, D-50937 Cologne, Germany.
[Schramm, Alexander] Univ Childrens Hosp, Dept Pediat Oncol & Hematol, D-45147 Essen, Germany.
[Schulte, Johannes H.] German Canc Consortium DKTK, D-10117 Berlin, Germany.
[Schulte, Johannes H.] German Canc Res Ctr, D-69120 Heidelberg, Germany.
[Herrmann, Carl] Heidelberg Univ, Inst Pharm & Mol Biotechnol, D-69120 Heidelberg, Germany.
[Herrmann, Carl] Heidelberg Univ, Bioquant Ctr, D-69120 Heidelberg, Germany.
[Herrmann, Carl] German Canc Res Ctr, Div Theoret Bioinformat, D-69120 Heidelberg, Germany.
[Fischer, Matthias] Max Planck Inst Metab Res, D-50931 Cologne, Germany.
RP Fischer, M (reprint author), Univ Cologne, Ctr Mol Med Cologne CMMC, D-50931 Cologne, Germany.
EM mpeifer@uni-koeln.de; frank.westermann@dkfz-heidelberg.de;
roman.thomas@uni-koeln.de; matthias.fischer@uk-koeln.de
RI Herrmann, Carl/H-5859-2011; Hofer, Thomas/G-5665-2013; Ikram,
Fakhera/E-3162-2017; THIERRY-MIEG, Jean/F-1975-2017;
OI Hofer, Thomas/0000-0003-3560-8780; THIERRY-MIEG,
Jean/0000-0002-0396-6789; Hertwig, Falk/0000-0003-4784-6516
FU German Cancer Aid [110122]; German Ministry of Science and Education
(BMBF) as part of the e:Med initiative [01ZX1303A, 01ZX1406, 01ZX1307D];
BMBF [0316076A]; European Union [259348]; Fordergesellschaft
Kinderkrebs-Neuroblastom-Forschung e.V.; German-Israeli Helmholtz
Research School in Cancer Biology; Volkswagenstiftung (Lichtenberg
Program); Center for Molecular Medicine Cologne
FX We are indebted to the patients and their parents for making available
the tumour specimens analysed in this study. We thank the German
Neuroblastoma Biobank for providing samples from patients. The
Institutional Review Board approved collection and use of all specimens
in this study. We also thank our colleagues N. Hemstedt, H. Duren, E.
Hess, J. Kreth, and J. Gopalakrishnan; and our collaboration partners I.
Amit and F. Paul at the Weizmann Institute of Science for technical
assistance. We further acknowledge the Center for Molecular Medicine
Cologne light microscope facility for helping us to obtain high-quality
data of FISH analyses, and S. Wolf and the Next Generation Sequencing
Unit at the German Cancer Research Center (DKFZ) for sequencing. This
work was supported by the German Cancer Aid (grant 110122) to M.F.,
F.W., J.H.S., A.S., and S.A.; the German Ministry of Science and
Education (BMBF) as part of the e:Med initiative (grant 01ZX1303A to
M.P., M.F.,J.H.S., R.B., U.L., and R.K.T., grant 01ZX1406 to M.P., and
grant01ZX1307D to M.F. and F.W.); the BMBF (grant 0316076A to F.W.); the
European Union (grant 259348 to F.W); the Fordergesellschaft
Kinderkrebs-Neuroblastom-Forschung e.V. (to M.F); the German-Israeli
Helmholtz Research School in Cancer Biology (to M.G. and F.W.); the
Volkswagenstiftung (Lichtenberg Program) (to M.R.S.); and the Center for
Molecular Medicine Cologne.
NR 24
TC 39
Z9 42
U1 8
U2 26
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0028-0836
EI 1476-4687
J9 NATURE
JI Nature
PD OCT 29
PY 2015
VL 526
IS 7575
BP 700
EP 704
DI 10.1038/nature14980
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CU8ZH
UT WOS:000363832100048
PM 26466568
ER
PT J
AU Pavletic, AJ
AF Pavletic, Adriana J.
TI An Integrated View of Potassium Homeostasis
SO NEW ENGLAND JOURNAL OF MEDICINE
LA English
DT Letter
ID HYPERKALEMIA
C1 NIMH, Bethesda, MD 20892 USA.
RP Pavletic, AJ (reprint author), NIMH, Bethesda, MD 20892 USA.
EM pavletia@mail.nih.gov
FU Intramural NIH HHS [Z99 MH999999]
NR 3
TC 0
Z9 0
U1 0
U2 2
PU MASSACHUSETTS MEDICAL SOC
PI WALTHAM
PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA
SN 0028-4793
EI 1533-4406
J9 NEW ENGL J MED
JI N. Engl. J. Med.
PD OCT 29
PY 2015
VL 373
IS 18
BP 1786
EP 1787
PG 3
WC Medicine, General & Internal
SC General & Internal Medicine
GA CU4QH
UT WOS:000363514100029
PM 26510041
ER
PT J
AU Berezhkovskii, AM
Dagdug, L
Bezrukov, SM
AF Berezhkovskii, Alexander M.
Dagdug, Leonardo
Bezrukov, Sergey M.
TI Range of applicability of modified Fick-Jacobs equation in two
dimensions
SO JOURNAL OF CHEMICAL PHYSICS
LA English
DT Article
ID DIFFUSION
AB Axial diffusion in a two-dimensional channel of smoothly varying geometry can be approximately described as one-dimensional diffusion in the entropy potential with position-dependent effective diffusivity by means of the modified Fick-Jacobs equation. In this paper, Brownian dynamics simulations are used to study the range of applicability of such a description, as well as the accuracy of the expressions for the effective diffusivity proposed by different researchers. (C) 2015 AIP Publishing LLC.
C1 [Berezhkovskii, Alexander M.; Dagdug, Leonardo; Bezrukov, Sergey M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Phys Biol, NIH, Bethesda, MD 20892 USA.
[Berezhkovskii, Alexander M.; Dagdug, Leonardo] NIH, Ctr Informat Technol, Div Computat Biosci, Math & Stat Comp Lab, Bethesda, MD 20892 USA.
[Dagdug, Leonardo] Univ Autonoma Metropolitana Iztapalapa, Dept Phys, Mexico City 09340, DF, Mexico.
RP Berezhkovskii, AM (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Phys Biol, NIH, Bethesda, MD 20892 USA.
OI Bezrukov, Sergey/0000-0002-8209-8050
FU Consejo Nacional de Ciencia y Tecnologia (CONACyT) [176452]; Division of
Basic Science and Engineering (CBI); Intramural Research Program of the
NIH; Center for Information Technology; Eunice Kennedy Shriver National
Institute of Child Health and Human Development
FX This study was supported by the Intramural Research Program of the NIH,
Center for Information Technology, and Eunice Kennedy Shriver National
Institute of Child Health and Human Development. L.D. thanks Consejo
Nacional de Ciencia y Tecnologia (CONACyT) (under Grant No. 176452) and
the Division of Basic Science and Engineering (CBI), for partial
support.
NR 19
TC 4
Z9 4
U1 2
U2 5
PU AMER INST PHYSICS
PI MELVILLE
PA 1305 WALT WHITMAN RD, STE 300, MELVILLE, NY 11747-4501 USA
SN 0021-9606
EI 1089-7690
J9 J CHEM PHYS
JI J. Chem. Phys.
PD OCT 28
PY 2015
VL 143
IS 16
AR 164102
DI 10.1063/1.4934223
PG 5
WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical
SC Chemistry; Physics
GA CV4KN
UT WOS:000364235800002
PM 26520493
ER
PT J
AU Abrams, LR
McBride, CM
Hooker, GW
Cappella, JN
Koehly, LM
AF Abrams, Leah R.
McBride, Colleen M.
Hooker, Gillian W.
Cappella, Joseph N.
Koehly, Laura M.
TI The Many Facets of Genetic Literacy: Assessing the Scalability of
Multiple Measures for Broad Use in Survey Research
SO PLOS ONE
LA English
DT Article
ID PUBLIC KNOWLEDGE; SCALE ANALYSIS; DECISION AID; HEALTH; FORMAT; IMPACT;
COMMUNICATION; PREFERENCES; INFORMATION; PERCEPTIONS
AB Objectives
To determine how three dimensions of genetic literacy (familiarity, skills, and factual knowledge) fit the hierarchy of knowledge outlined in E.M. Rogers' Diffusion of Innovations to better conceptualize lay understandings of genomics.
Methods
A consumer panel representing the US adult population (N = 1016) completed an electronic survey in November 2013. Adjusting for education, we used correlations, principle components analysis, Mokken Scale tests, and linear regressions to assess how scores on the three genetic literacy sub-dimensions fit an ordered scale.
Results
The three scores significantly loaded onto one factor, even when adjusting for education. Analyses revealed moderate strength in scaling (0.416, p<0.001) and a difficulty ordering that matched Rogers' hierarchy (knowledge more difficult than skills, followed by familiarity). Skills scores partially mediated the association between familiarity and knowledge with a significant indirect effect (0.241, p<0.001).
Conclusion
We established an ordering in genetic literacy sub-dimensions such that familiarity with terminology precedes skills using information, which in turn precedes factual knowledge. This ordering is important to contextualizing previous findings, guiding measurement in future research, and identifying gaps in the understanding of genomics relevant to the demands of differing applications.
C1 [Abrams, Leah R.; Koehly, Laura M.] NHGRI, Social & Behav Res Branch, Bethesda, MD 20892 USA.
[McBride, Colleen M.] Emory Univ, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA.
[Hooker, Gillian W.] NextGxDx, Franklin, TN USA.
[Cappella, Joseph N.] Univ Penn, Annenberg Sch Commun, Philadelphia, PA 19104 USA.
RP Koehly, LM (reprint author), NHGRI, Social & Behav Res Branch, Bethesda, MD 20892 USA.
EM koehlyl@mail.nih.gov
FU Intramural Research Program of the National Human Genome Research
Institute; NextGxDx
FX This work was funded by the Intramural Research Program of the National
Human Genome Research Institute. NextGxDx provided support in the form
of salaries for authors [GWH], but did not have any additional role in
the study design, data collection and analysis, decision to publish, or
preparation of the manuscript. The specific roles of this author are
articulated in the "author contributions" section.
NR 36
TC 1
Z9 1
U1 2
U2 4
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD OCT 28
PY 2015
VL 10
IS 10
AR e0141532
DI 10.1371/journal.pone.0141532
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CV0DL
UT WOS:000363918100099
PM 26510161
ER
PT J
AU Alonso, WJ
Rabaa, MA
Giglio, R
Miller, MA
Schuck-Paim, C
AF Alonso, Wladimir J.
Rabaa, Maia A.
Giglio, Ricardo
Miller, Mark A.
Schuck-Paim, Cynthia
TI Modeling the Impact of Alternative Immunization Strategies: Using
Matrices as Memory Lanes
SO PLOS ONE
LA English
DT Article
ID MEASLES EPIDEMICS; DYNAMICS; VACCINATION
AB Existing modeling approaches are divided between a focus on the constitutive (micro) elements of systems or on higher (macro) organization levels. Micro-level models enable consideration of individual histories and interactions, but can be unstable and subject to cumulative errors. Macro-level models focus on average population properties, but may hide relevant heterogeneity at the micro-scale. We present a framework that integrates both approaches through the use of temporally structured matrices that can take large numbers of variables into account. Matrices are composed of several bidimensional (timexage) grids, each representing a state (e.g. physiological, immunological, socio-demographic). Time and age are primary indices linking grids. These matrices preserve the entire history of all population strata and enable the use of historical events, parameters and states dynamically in the modeling process. This framework is applicable across fields, but particularly suitable to simulate the impact of alternative immunization policies. We demonstrate the framework by examining alternative strategies to accelerate measles elimination in 15 developing countries. The model recaptured long-endorsed policies in measles control, showing that where a single routine measles-containing vaccine is employed with low coverage, any improvement in coverage is more effective than a second dose. It also identified an opportunity to save thousands of lives in India at attractively low costs through the implementation of supplementary immunization campaigns. The flexibility of the approach presented enables estimating the effectiveness of different immunization policies in highly complex contexts involving multiple and historical influences from different hierarchical levels.
C1 [Alonso, Wladimir J.; Rabaa, Maia A.; Miller, Mark A.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Alonso, Wladimir J.; Schuck-Paim, Cynthia] Origem Sci Epidemiol & Modeling, Sao Paulo, SP, Brazil.
[Rabaa, Maia A.] Univ Oxford, Clin Res Unit, Ho Chi Minh City, Vietnam.
[Giglio, Ricardo] Univ Fed Santa Catarina, Dept Econ, Florianopolis, SC, Brazil.
RP Alonso, WJ (reprint author), NIH, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA.
EM Wladimir.Alonso@nih.gov
OI Rabaa, Maia/0000-0003-0529-2228
FU Fogarty International Center, National Institutes of Health; Origem
Scientifica (Sao Paulo, Brazil)
FX This work was supported by intramural funds from Fogarty International
Center, National Institutes of Health. CSP and WJA were also funded by
Origem Scientifica (Sao Paulo, Brazil), a company specializing in the
analyses of global health data. The funder provided support in the form
of salaries for authors [CSP, WJA], but did not have any additional role
in the study design, data collection and analysis, decision to publish,
or preparation of the manuscript.
NR 25
TC 0
Z9 0
U1 0
U2 0
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD OCT 28
PY 2015
VL 10
IS 10
AR e0141147
DI 10.1371/journal.pone.0141147
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CV0DL
UT WOS:000363918100057
PM 26509976
ER
PT J
AU Jaekl, P
Seidlitz, J
Harris, LR
Tadin, D
AF Jaekl, Philip
Seidlitz, Jakob
Harris, Laurence R.
Tadin, Duje
TI Audiovisual Delay as a Novel Cue to Visual Distance
SO PLOS ONE
LA English
DT Article
ID MULTISENSORY INTEGRATION; PERCEPTION; SOUND; MOTION; CAPTURE;
SIMULTANEITY; PERSPECTIVE; CONGRUENCY; ATTENTION; OCCLUSION
AB For audiovisual sensory events, sound arrives with a delay relative to light that increases with event distance. It is unknown, however, whether humans can use these ubiquitous sound delays as an information source for distance computation. Here, we tested the hypothesis that audiovisual delays can both bias and improve human perceptual distance discrimination, such that visual stimuli paired with auditory delays are perceived as more distant and are thereby an ordinal distance cue. In two experiments, participants judged the relative distance of two repetitively displayed three-dimensional dot clusters, both presented with sounds of varying delays. In the first experiment, dot clusters presented with a sound delay were judged to be more distant than dot clusters paired with equivalent sound leads. In the second experiment, we confirmed that the presence of a sound delay was sufficient to cause stimuli to appear as more distant. Additionally, we found that ecologically congruent pairing of more distant events with a sound delay resulted in an increase in the precision of distance judgments. A control experiment determined that the sound delay duration influencing these distance judgments was not detectable, thereby eliminating decision-level influence. In sum, we present evidence that audiovisual delays can be an ordinal cue to visual distance.
C1 [Jaekl, Philip; Seidlitz, Jakob; Tadin, Duje] Univ Rochester, Ctr Visual Sci, Rochester, NY 14627 USA.
[Jaekl, Philip; Seidlitz, Jakob; Tadin, Duje] Univ Rochester, Dept Brain & Cognit Sci, Rochester, NY USA.
[Seidlitz, Jakob] NIMH, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA.
[Harris, Laurence R.] York Univ, Ctr Vis Res, Toronto, ON M3J 2R7, Canada.
[Harris, Laurence R.] York Univ, Dept Psychol, Toronto, ON M3J 2R7, Canada.
[Harris, Laurence R.] York Univ, Dept Biol & Kinesiol, Toronto, ON M3J 2R7, Canada.
[Tadin, Duje] Univ Rochester, Sch Med, Dept Ophthalmol, Rochester, NY USA.
RP Jaekl, P (reprint author), Univ Rochester, Ctr Visual Sci, Rochester, NY 14627 USA.
EM pjaekl@cvs.rochester.edu
FU National Institutes of Health; Center for Visual Science (University of
Rochester) [NEI P30 EY001319]
FX Support was provided by the National Institutes of Health and the Center
for Visual Science (University of Rochester) core grant: NEI P30
EY001319. The funders had no role in study design, data collection and
analysis, decision to publish, or preparation of the manuscript.
NR 38
TC 1
Z9 1
U1 0
U2 4
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD OCT 28
PY 2015
VL 10
IS 10
AR e0141125
DI 10.1371/journal.pone.0141125
PG 12
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CV0DL
UT WOS:000363918100055
PM 26509795
ER
PT J
AU Xiong, LH
Cui, R
Zhang, ZL
Tu, JW
Shi, YB
Pang, DW
AF Xiong, Ling-Hong
Cui, Ran
Zhang, Zhi-Ling
Tu, Jia-Wei
Shi, Yun-Bo
Pang, Dai-Wen
TI Harnessing Intracellular Biochemical Pathways for In Vitro Synthesis of
Designer Tellurium Nanorods
SO SMALL
LA English
DT Article
DE designer nanomaterials; intracellular biochemical pathways; in vitro
synthesis; nanorods; Staphylococcus aureus
ID QUANTUM DOTS; SACCHAROMYCES-CEREVISIAE; CDSE NANOCRYSTALS; YEAST-CELLS;
NANOPARTICLES; GROWTH; GOLD
AB Synthesizing nanomaterials of desired properties is a big challenge, which requires extremely harsh conditions and/or use of toxic materials. More recently developed in vivo methods have brought a different set of problems such as separation and purification of nanomaterials made in vivo. Here, a novel approach that harnesses cellular pathways for in vitro synthesis of high-quality tellurium nanorods with tunable lengths and optical properties is reported. It is first demonstrated that in vivo biochemical pathways could be used to synthesize Te nanorods via the intracellular reduction of TeO3 (2-) in living Staphylococcus aureus cells. The pathways to set up a quasi-biological system for Te precursor formation are then utilized, which could further synthesize Te nanorods in vitro. This allows to successfully synthesize in vitro, under routine laboratory conditions, Te nanorods with uniform and tunable lengths, ranging from about 10 to 200 nm, and controllable optical properties with high molar extinction coefficients. The approach here should open new avenues for controllable, facile, and efficient synthesis of designer nanomaterials for diverse industrial and biomedical applications.
C1 [Xiong, Ling-Hong; Cui, Ran; Zhang, Zhi-Ling; Tu, Jia-Wei; Pang, Dai-Wen] Wuhan Univ, Inst Adv Studies, State Key Lab Virol,Coll Chem & Mol Sci, Key Lab Analyt Chem Biol & Med,Minist Educ, Wuhan 430072, Peoples R China.
[Xiong, Ling-Hong; Cui, Ran; Zhang, Zhi-Ling; Tu, Jia-Wei; Pang, Dai-Wen] Wuhan Univ, Wuhan Inst Biotechnol, Wuhan 430072, Peoples R China.
[Shi, Yun-Bo] NICHD, Sect Mol Morphogenesis, PCRM, NIH, Bethesda, MD 20892 USA.
RP Pang, DW (reprint author), Wuhan Univ, Inst Adv Studies, State Key Lab Virol,Coll Chem & Mol Sci, Key Lab Analyt Chem Biol & Med,Minist Educ, Wuhan 430072, Peoples R China.
EM dwpang@whu.edu.cn
RI Zhang, Zhi-Ling/B-3135-2010
OI Zhang, Zhi-Ling/0000-0001-7807-2264
FU National Basic Research Program of China (973 Program) [2011CB933600];
111 Project [111-2-10]; Collaborative Innovation Center for Chemistry
and Molecular Medicine; Intramural Research Program of NICHD, NIH, USA
FX This work was supported by the National Basic Research Program of China
(973 Program, No. 2011CB933600) and the 111 Project (111-2-10), and
Collaborative Innovation Center for Chemistry and Molecular Medicine.
Y.-B.S. was supported by the Intramural Research Program of NICHD, NIH,
USA.
NR 25
TC 2
Z9 3
U1 11
U2 35
PU WILEY-V C H VERLAG GMBH
PI WEINHEIM
PA POSTFACH 101161, 69451 WEINHEIM, GERMANY
SN 1613-6810
EI 1613-6829
J9 SMALL
JI Small
PD OCT 28
PY 2015
VL 11
IS 40
BP 5416
EP 5422
DI 10.1002/smll.201500816
PG 7
WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience &
Nanotechnology; Materials Science, Multidisciplinary; Physics, Applied;
Physics, Condensed Matter
SC Chemistry; Science & Technology - Other Topics; Materials Science;
Physics
GA CU4CP
UT WOS:000363474200010
PM 26313741
ER
PT J
AU Narayanan, SP
Singh, S
Gupta, A
Yadav, S
Singh, SR
Shukla, S
AF Narayanan, Sathiya Pandi
Singh, Smriti
Gupta, Amit
Yadav, Sandhya
Singh, Shree Ram
Shukla, Sanjeev
TI Integrated genomic analyses identify KDM1A's role in cell proliferation
via modulating E2F signaling activity and associate with poor clinical
outcome in oral cancer
SO CANCER LETTERS
LA English
DT Article
DE Oral cancer; Histone demethylase; KDM1A; E2F1 signaling; Cell
proliferation
ID PROTEIN LYSINE METHYLATION; EPITHELIAL OVARIAN-CANCER; BREAST-CANCER;
EPIGENETIC MODIFICATIONS; HISTONE DEMETHYLASES; GENE-EXPRESSION;
PROSTATE-CANCER; STEM-CELLS; LSD1; TRANSCRIPTION
AB The histone demethylase KDM1A specifically demethylates lysine residues and its deregulation has been implicated in the initiation and progression of various cancers. However, KDM1A's molecular role and its pathological consequences, and prognostic significance in oral cancer remain less understood. In the present study, we sought to investigate the expression of KDM1A and its downstream role in oral cancer pathogenesis. By comparing mRNA expression profiles, we identified an elevated KDM1A expression in oral tumors when compared to normal oral tissues. In silica pathway prediction identified the association between KDM1A and E2F1 signaling in oral cancer. Pathway scanning, functional annotation analysis and In vitro assays showed the KDM1A's involvement in oral cancer cell proliferation and the cell cycle. Moreover, real time PCR and luciferase assays confirmed KDM1A's role in regulation of E2F1 signaling activity in oral cancer. Elevated KDM1A expression is associated with poor clinical outcome in oral cancer. Our data indicate that deregulated KDM1A expression is positively associated with proliferative phenotype of oral cancer and confers poor clinical outcome. These cumulative data suggest that KDM1A might be a potential diagnostic and therapeutic target for oral cancer. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
C1 [Narayanan, Sathiya Pandi; Singh, Smriti; Gupta, Amit; Yadav, Sandhya; Shukla, Sanjeev] IISERB, ERPL, Bhopal, Madhya Pradesh, India.
[Singh, Shree Ram] NCI, Basic Res Lab, Ctr Canc Res, Frederick, MD 21702 USA.
RP Shukla, S (reprint author), IISERB, ERPL, Bhopal, Madhya Pradesh, India.
EM singhshr@mail.nih.gov; sanjeevs@iiserb.ac.in
RI Singh, Shree Ram/B-7614-2008;
OI Singh, Shree Ram/0000-0001-6545-583X; Shukla,
Sanjeev/0000-0003-3361-0588
FU IISER Bhopal; Ministry of Human Resource Development; Council of
Scientific & Industrial Research
FX We thank IISER Bhopal for Intramural research funds. We thank Ministry
of Human Resource Development for fellowships to Dr. Sathiya Pandi, Ms.
Smriti Singh and Mr. Amit Gupta. We thank Council of Scientific &
Industrial Research for fellowship to Ms. Sandhya Yadav.
NR 55
TC 1
Z9 1
U1 1
U2 14
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0304-3835
EI 1872-7980
J9 CANCER LETT
JI Cancer Lett.
PD OCT 28
PY 2015
VL 367
IS 2
BP 162
EP 172
DI 10.1016/j.canlet.2015.07.022
PG 11
WC Oncology
SC Oncology
GA CQ9QJ
UT WOS:000360949600011
PM 26225839
ER
PT J
AU Abraham, TM
Pedley, A
Massaro, JM
Hoffmann, U
Fox, CS
AF Abraham, Tobin M.
Pedley, Alison
Massaro, Joseph M.
Hoffmann, Udo
Fox, Caroline S.
TI Association Between Visceral and Subcutaneous Adipose Depots and
Incident Cardiovascular Disease Risk Factors
SO CIRCULATION
LA English
DT Article
DE adipose tissue; epidemiology; population; risk factors
ID INSULIN-RESISTANCE; JAPANESE-AMERICANS; TISSUE VOLUMES; HEART; FAT;
FRAMINGHAM; INFLAMMATION; OBESITY; HYPERTENSION; ADIPOKINES
AB Background-Visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) vary in volume and quality. We evaluated whether fat volume or attenuation (indirect measure of quality) predicts metabolic risk factor changes.
Methods and Results-Framingham Heart Study Multi-detector Computed Tomography Substudy participants (n=1730, 45% women) were followed up over a mean of 6.2 years. Baseline VAT and SAT volume (in cm(3)) and attenuation (in Hounsfield units) were assessed. Outcomes included blood pressure, lipids, and glucose. We constructed multivariable regression models predicting change from baseline to follow-up. Baseline VAT was associated with metabolic risk factors at follow-up. Per 500-cm(3) increase in baseline VAT, glucose was 2.34 mg/dL higher (95% confidence interval, 1.712.97) and high-density lipoprotein was 1.62 mg/dL lower (95% confidence interval, 0.97-2.28) in women (P<0.0001 for both). These findings remained significant after adjustment for body mass index. Results for SAT were similar although less striking. Lower (more negative) fat attenuation was associated with more adverse metabolic profiles at follow-up. For example, per 5-unit decrease in baseline VAT Hounsfield units, log triglycerides increased by 0.08 mg/dL (95% confidence interval, 0.05-0.12; P=0.005), which remained significant after adjustment for baseline VAT. Among men, VAT and SAT Hounsfield units were associated with changes in cardiovascular disease risk factors but were mostly attenuated after baseline volume adjustment.
Conclusions-VAT volume and SAT volume are associated with incident metabolic risk factors beyond overall adiposity. Decreases in fat attenuation are also associated with incident risk factors. These findings suggest that both volume and quality of VAT and SAT contribute to metabolic risk.
C1 [Abraham, Tobin M.; Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Abraham, Tobin M.; Fox, Caroline S.] NHLBI, Bethesda, MD USA.
[Abraham, Tobin M.; Pedley, Alison; Fox, Caroline S.] Brigham & Womens Hosp, Dept Endocrinol Hypertens & Diabet, Boston, MA USA.
[Abraham, Tobin M.; Pedley, Alison; Hoffmann, Udo; Fox, Caroline S.] Harvard Univ, Sch Med, Boston, MA USA.
[Massaro, Joseph M.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA.
[Hoffmann, Udo] Massachusetts Gen Hosp, Dept Radiol, Boston, MA USA.
RP Fox, CS (reprint author), Framingham Heart Dis Epidemiol Study, 73 Mt Wayte Ave,Ste 2, Framingham, MA 01702 USA.
EM foxca@nhlbi.nih.gov
FU National Institutes of Health; [N01-HC-25195]
FX The FHS of the National Heart, Lung, and Blood Institute is supported by
contract N01-HC-25195. Dr Abraham is supported by an National Institutes
of Health-sponsored T32 training grant.
NR 27
TC 16
Z9 16
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0009-7322
EI 1524-4539
J9 CIRCULATION
JI Circulation
PD OCT 27
PY 2015
VL 132
IS 17
BP 1639
EP 1647
DI 10.1161/CIRCULATIONAHA.114.015000
PG 9
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA DC5IU
UT WOS:000369255500013
PM 26294660
ER
PT J
AU Roth, GA
Huffman, MD
Moran, AE
Feigin, V
Mensah, GA
Naghavi, M
Murray, CJL
AF Roth, Gregory A.
Huffman, Mark D.
Moran, Andrew E.
Feigin, Valery
Mensah, George A.
Naghavi, Mohsen
Murray, Christopher J. L.
TI Global and Regional Patterns in Cardiovascular Mortality From 1990 to
2013
SO CIRCULATION
LA English
DT Article
DE cardiovascular diseases; epidemiology; global health; mortality
ID CORONARY-HEART-DISEASE; SUB-SAHARAN AFRICA; RISK-FACTORS; EPIDEMIOLOGIC
TRANSITION; MYOCARDIAL-INFARCTION; NONCOMMUNICABLE DISEASES;
INTERNATIONAL TRENDS; DEVELOPING-COUNTRIES; SYSTEMATIC ANALYSIS; INCOME
COUNTRIES
AB There is a global commitment to reduce premature cardiovascular diseases (CVDs) 25% by 2025. CVD mortality rates have declined dramatically over the past 2 decades, yet the number of life years lost to premature CVD deaths is increasing in low-and middle-income regions. Ischemic heart disease and stroke remain the leading causes of premature death in the world; however, there is wide regional variation in these patterns. Some regions, led by Central Asia, face particularly high rates of premature death from ischemic heart disease. Sub-Saharan Africa and Asia suffer disproportionately from death from stroke. The purpose of the present report is to (1) describe global trends and regional variation in premature mortality attributable to CVD, (2) review past and current approaches to the measurement of these trends, and (3) describe the limitations of existing models of epidemiological transitions for explaining the observed distribution and trends of CVD mortality. We describe extensive variation both between and within regions even while CVD remains a dominant cause of death. Policies and health interventions will need to be tailored and scaled for a broad range of local conditions to achieve global goals for the improvement of cardiovascular health.
C1 [Roth, Gregory A.; Naghavi, Mohsen; Murray, Christopher J. L.] Univ Washington, Seattle, WA 98121 USA.
[Huffman, Mark D.] Northwestern Univ, Chicago, IL 60611 USA.
[Moran, Andrew E.] Columbia Univ, Dept Med, Div Gen Med, New York, NY USA.
[Feigin, Valery] Auckland Univ Technol, Fac Hlth & Environm Sci, Natl Inst Stroke & Appl Neurosci, Auckland, New Zealand.
[Mensah, George A.] NHLBI, Ctr Translat Res & Implementat Sci, NIH, Bethesda, MD USA.
RP Roth, GA (reprint author), Univ Washington, Inst Hlth Metr & Evaluat, Div Cardiol, Dept Med, 2301 5th Ave,Suite 600, Seattle, WA 98121 USA.
EM rothg@uw.edu
OI Huffman, Mark/0000-0001-7412-2519
FU Bill and Melinda Gates Foundation; American Heart Association Western
States Postdoctoral Fellowship; National Heart, Lung, and Blood
Institute [4R00HL107749-03, K08 HL089675-01A1]; Columbia University
Irving Scholarship
FX This work was supported by the Bill and Melinda Gates Foundation, an
American Heart Association Western States Postdoctoral Fellowship (to Dr
Roth), the National Heart, Lung, and Blood Institute (4R00HL107749-03;
to Dr Huffman), a National Heart, Lung, and Blood Institute award (K08
HL089675-01A1) and a Columbia University Irving Scholarship (to Dr.
Moran).
NR 56
TC 32
Z9 33
U1 3
U2 14
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0009-7322
EI 1524-4539
J9 CIRCULATION
JI Circulation
PD OCT 27
PY 2015
VL 132
IS 17
BP 1667
EP 1678
DI 10.1161/CIRCULATIONAHA.114.008720
PG 12
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA DC5IU
UT WOS:000369255500015
PM 26503749
ER
PT J
AU Ziats, MN
Grosvenor, LP
Rennert, OM
AF Ziats, M. N.
Grosvenor, L. P.
Rennert, O. M.
TI Functional genomics of human brain development and implications for
autism spectrum disorders
SO TRANSLATIONAL PSYCHIATRY
LA English
DT Review
ID LONG NONCODING RNAS; LYMPHOBLASTOID CELL-LINES; GENE REGULATORY
NETWORKS; STEM-CELLS; OLIGODENDROCYTE DIFFERENTIATION; COEXPRESSION
NETWORKS; CORTICAL DEVELOPMENT; PREFRONTAL CORTEX; HUMAN TISSUES;
EXPRESSION
AB Transcription of the inherited DNA sequence into copies of messenger RNA is the most fundamental process by which the genome functions to guide development. Encoded sequence information, inherited epigenetic marks and environmental influences all converge at the level of mRNA gene expression to allow for cell-type-specific, tissue-specific, spatial and temporal patterns of expression. Thus, the transcriptome represents a complex interplay between inherited genomic structure, dynamic experiential demands and external signals. This property makes transcriptome studies uniquely positioned to provide insight into complex genetic-epigenetic-environmental processes such as human brain development, and disorders with non-Mendelian genetic etiologies such as autism spectrum disorders. In this review, we describe recent studies exploring the unique functional genomics profile of the human brain during neurodevelopment. We then highlight two emerging areas of research with great potential to increase our understanding of functional neurogenomics-non-coding RNA expression and gene interaction networks. Finally, we review previous functional genomics studies of autism spectrum disorder in this context, and discuss how investigations at the level of functional genomics are beginning to identify convergent molecular mechanisms underlying this genetically heterogeneous disorder.
C1 [Ziats, M. N.; Rennert, O. M.] NICHHD, Lab Clin & Dev Genom, NIH, Bethesda, MD 20814 USA.
[Ziats, M. N.] Univ Cambridge, Robinson Coll, Cambridge CB2 1TN, Cambs, England.
[Ziats, M. N.] Baylor Coll Med MSTP, Houston, TX USA.
[Grosvenor, L. P.] NIMH, Pediat & Dev Neurosci Branch, NIH, Bethesda, MD 20892 USA.
RP Ziats, MN (reprint author), NICHHD, Lab Clin & Dev Genom, NIH, 49 Convent Dr,Bldg 49,Room 2C08, Bethesda, MD 20814 USA.
EM ziats@bcm.edu
FU Intramural Research Program at the National Institute of Child Health
and Human Development; Baylor College of Medicine MSTP; NIH-University
of Cambridge Biomedical Scholars Program; National Institute of Mental
Health
FX The Intramural Research Program at the National Institute of Child
Health and Human Development supported this work. MNZ was also supported
by Baylor College of Medicine MSTP and the NIH-University of Cambridge
Biomedical Scholars Program. LPG was funded by the National Institute of
Mental Health. The funders had no role in study design, data collection
and analysis, decision to publish or preparation of the manuscript. We
apologize for unintentionally omitting other relevant work because of
space limitations. We would like to thank Jeremy Swan for help with
figure generation.
NR 123
TC 4
Z9 4
U1 3
U2 9
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 2158-3188
J9 TRANSL PSYCHIAT
JI Transl. Psychiatr.
PD OCT 27
PY 2015
VL 5
AR e665
DI 10.1038/tp.2015.153
PG 10
WC Psychiatry
SC Psychiatry
GA DA2ZF
UT WOS:000367665000002
PM 26506051
ER
PT J
AU Hausmann, C
Temme, A
Cordes, N
Eke, I
AF Hausmann, Christina
Temme, Achim
Cordes, Nils
Eke, Iris
TI ILKAP, ILK and PINCH1 control cell survival of p53-wildtype glioblastoma
cells after irradiation
SO ONCOTARGET
LA English
DT Article
DE ILKAP; DNA repair; radioresistance; ILK; PINCH1
ID INTEGRIN-LINKED KINASE; DOUBLE-STRAND BREAKS; IONIZING-RADIATION;
CARCINOMA-CELLS; PROTEIN PHOSPHATASE; DNA-PKCS; IN-VITRO;
DOWN-REGULATION; CANCER CELLS; P53
AB The prognosis is generally poor for patients suffering from glioblastoma multiforme (GBM) due to radiation and drug resistance. Prosurvival signaling originating from focal adhesion hubs essentially contributes to therapy resistance and tumor aggressiveness. As the underlying molecular mechanisms remain largely elusive, we addressed whether targeting of the focal adhesion proteins particularly interesting new cysteine-histidine-rich 1 (PINCH1), integrin-linked kinase (ILK) and ILK associated phosphatase (ILKAP) modulates GBM cell radioresistance. Intriguingly, PINCH1, ILK and ILKAP depletion sensitized p53-wildtype, but not p53-mutant, GBM cells to radiotherapy. Concomitantly, these cells showed inactivated Glycogen synthase kinase-3 beta (GSK3 beta) and reduced proliferation. For PINCH1 and ILKAP knockdown, elevated levels of radiation-induced gamma H2AX/53BP1-positive foci, as a marker for DNA double strand breaks, were observed. Mechanistically, we identified radiation-induced phosphorylation of DNA protein kinase (DNAPK), an important DNA repair protein, to be dependent on ILKAP. This interaction was fundamental to radiation survival of p53-wildtype GBM cells. Conclusively, our data suggest an essential role of PINCH1, ILK and ILKAP for the radioresistance of p53-wildtype GBM cells and provide evidence for DNAPK functioning as a central mediator of ILKAP signaling. Strategies for targeting focal adhesion proteins in combination with radiotherapy might be a promising approach for patients with GBM.
C1 [Hausmann, Christina; Cordes, Nils; Eke, Iris] Tech Univ Dresden, Med Fac Carl Gustav Carus, OncoRay Natl Ctr Radiat Res Oncol, D-01307 Dresden, Germany.
[Temme, Achim] Tech Univ Dresden, Univ Hosp Carl Gustav Carus, Dept Neurosurg, Sect Expt Neurosurg Tumor Immunol, D-01307 Dresden, Germany.
[Cordes, Nils] Tech Univ Dresden, Univ Hosp, Dept Radiat Oncol, D-01307 Dresden, Germany.
[Cordes, Nils] Tech Univ Dresden, Med Fac Carl Gustav Carus, D-01307 Dresden, Germany.
[Cordes, Nils] Helmholtz Zentrum Dresden Rossendorf, Inst Radiooncol, D-01328 Dresden, Germany.
[Cordes, Nils] German Canc Consortium DKTK, D-01307 Dresden, Germany.
[Cordes, Nils] German Canc Res Ctr, D-69120 Heidelberg, Germany.
[Eke, Iris] NCI, Radiat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Cordes, N (reprint author), Tech Univ Dresden, Med Fac Carl Gustav Carus, OncoRay Natl Ctr Radiat Res Oncol, D-01307 Dresden, Germany.
EM Nils.Cordes@OncoRay.de; Iris.Eke@nih.gov
OI Cordes, Nils/0000-0001-5684-629X
FU Bundesministerium fur Bildung und Forschung (BMBF) [03ZIK041,
BMBF-02NUK006B]; Deutsche Forschungsgemeinschaft [CO668/4-1]; Deutsche
Krebshilfe [108976]; EFRE Europaische Fonds fur regionale Entwicklung;
Europa fordert Sachsen [100066308]; NIH Intramural Research Program,
National Cancer Institute, Center for Cancer Research
FX The authors were in part supported by a grant from the Bundesministerium
fur Bildung und Forschung (BMBF Contracts 03ZIK041 and BMBF-02NUK006B to
N.C.), the Deutsche Forschungsgemeinschaft (CO668/4-1 to N.C.), the
Deutsche Krebshilfe (108976 to N.C.), the EFRE Europaische Fonds fur
regionale Entwicklung, Europa fordert Sachsen (100066308) and by the NIH
Intramural Research Program, National Cancer Institute, Center for
Cancer Research (to I.E.).
NR 64
TC 1
Z9 1
U1 0
U2 2
PU IMPACT JOURNALS LLC
PI ALBANY
PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA
SN 1949-2553
J9 ONCOTARGET
JI Oncotarget
PD OCT 27
PY 2015
VL 6
IS 33
BP 34592
EP 34605
DI 10.18632/oncotarget.5423
PG 14
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA CY0PE
UT WOS:000366107200055
PM 26460618
ER
PT J
AU Miquelajauregui, A
Sandoval-Schaefer, T
Martinez-Armenta, M
Perez-Martinez, L
Carabez, A
Zhao, YG
Heide, M
Alvarez-Bolado, G
Varela-Echavarria, A
AF Miquelajauregui, Amaya
Sandoval-Schaefer, Teresa
Martinez-Armenta, Miriam
Perez-Martinez, Leonor
Carabez, Alfonso
Zhao, Yangu
Heide, Michael
Alvarez-Bolado, Gonzalo
Varela-Echavarria, Alfredo
TI LIM homeobox protein 5 (Lhx5) is essential for mamillary body
development
SO FRONTIERS IN NEUROANATOMY
LA English
DT Article
DE transcription factor; diencephalon; hypothalamus; mouse; embryonic
development
ID MAMMILLARY BODY; SONIC-HEDGEHOG; SPINAL-CORD; HYPOTHALAMIC DEVELOPMENT;
NEURON SUBPOPULATIONS; BRAIN-STEM; GENE LHX5; MOUSE; EXPRESSION;
FOREBRAIN
AB The mamillary body (MM) is a group of hypothalamic nuclei related to memory and spatial navigation that interconnects hippocampal, thalamic, and tegmental regions. Here we demonstrate that Lhx5, a LIM-HD domain transcription factor expressed early in the developing posterior hypothalamus, is required for the generation of the MM and its derived tracts. The MM markers Foxb1, Sim2, and Lhx1 are absent in Lhx5 knock out mice from early embryonic stages, suggesting abnormal specification of this region. This was supported by the absence of Nkx2,1 and expansion of Shh in the prospective mamillary area. Interestingly, we also found an ectopic domain expressing Lhx2 and Lhx9 along the anterio-posterior hypothalamic axis. Our results suggest that Lhx5 controls early aspects of hypothalamic development by regulating gene expression and cellular specification in the prospective MM.
C1 [Miquelajauregui, Amaya; Sandoval-Schaefer, Teresa; Carabez, Alfonso; Varela-Echavarria, Alfredo] Univ Nacl Autonoma Mexico, Inst Neurobiol, Dept Neurobiol Desarrollo & Neurofisiol, Queretaro, Mexico.
[Martinez-Armenta, Miriam; Perez-Martinez, Leonor] Univ Nacl Autonoma Mexico, Inst Biotechnol, Dept Med Mol & Bioproc, Lab Neuroinmunobiol, Cuernavaca 62191, Morelos, Mexico.
[Zhao, Yangu] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Genom Differentiat, NIH, Bethesda, MD USA.
[Heide, Michael; Alvarez-Bolado, Gonzalo] Heidelberg Univ, Inst Anat & Cell Biol, Heidelberg, Germany.
RP Miquelajauregui, A (reprint author), Univ Calif Los Angeles, Semel Inst, Ctr Autism Res & Treatment, 760 Westwood Plaza,Room A7-461, Los Angeles, CA 90095 USA.
EM amayam@ucla.edu; avarela@unam.mx
FU NICHD/NIH; Consejo Nacional de Ciencia y Tecnologia [CONACYT-232722,
249744]; DGAPA-UNAM [IN203713]; DGAPA-UNAM
FX The work was supported by funds from the intramural research program of
NICHD/NIH, Consejo Nacional de Ciencia y Tecnologia (CONACYT-232722 and
249744), and DGAPA-UNAM IN203713. AM was supported by a postdoctoral
fellowship from DGAPA-UNAM. Technical support was provided by Anaid
Antaramian Salas, Adriana Gonzalez Gallant, Pilar Galarza, Martin Garcia
Servin, Nydia Hernandez, Alberto Lara, and Omar Gonzalez. We thank Prof.
Jacques Michaud for kindly providing probes and Dorothy Pless for
editing of the manuscript.
NR 57
TC 0
Z9 0
U1 1
U2 3
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015,
SWITZERLAND
SN 1662-5129
J9 FRONT NEUROANAT
JI Front. Neuroanat.
PD OCT 27
PY 2015
VL 9
AR 136
DI 10.3389/fnana.2015.00136
PG 10
WC Anatomy & Morphology; Neurosciences
SC Anatomy & Morphology; Neurosciences & Neurology
GA CX6XM
UT WOS:000365845000001
PM 26578897
ER
PT J
AU Wang, HC
Nair, VS
Holland, AA
Capolicchio, S
Jessen, HJ
Johnson, MK
Shears, SB
AF Wang, Huanchen
Nair, Vasudha S.
Holland, Ashley A.
Capolicchio, Sarnanta
Jessen, Henning J.
Johnson, Michael K.
Shears, Stephen B.
TI Asp1 from Schizosaccharomyces pombe Binds a [2Fe-2S](2+) Cluster Which
Inhibits Inositol Pyrophosphate 1-Phosphatase Activity
SO BIOCHEMISTRY
LA English
DT Article
ID IRON-SULFUR CLUSTER; CONSERVED CYSTEINE RESIDUES; SITE-DIRECTED
MUTAGENESIS; RESONANCE RAMAN; DIPHOSPHOINOSITOL POLYPHOSPHATES;
CLOSTRIDIAL FERREDOXIN; 2FE-2S CLUSTERS; PROTEIN; ENZYMES;
IDENTIFICATION
AB Iron-sulfur (Fe-S) clusters are widely distributed protein cofactors that are vital to cellular biochemistry and the maintenance of bioenergetic homeostasis, but to our knowledge, they have never been identified in any phosphatase. Here, we describe an iron-sulfur cluster in Asp1, a dual-function kinase/phosphatase that regulates cell morphogenesis in Schizosaccharomyces pombe. Full-length Asp1, and its phosphatase domain (Asp1(371-920)), were each heterologously expressed in Escherichia coli. The phosphatase activity is exquisitely specific: it hydrolyzes the 1-diphosphate from just two members of the inositol pyrophosphate (PP-InsP) signaling family, namely, 1-InsP(7) and 1,5-InsP(8). We demonstrate that Asp1 does not hydrolyze either InsP(6), 2-InsP(7), 3-InsP(7), 4-InsP(7), 5-InsP(7), 6-InsP(7), or 3,5-InsP(8). We also recorded 1-phosphatase activity in a human homologue of Asp1, hPPIP5K1, which was heterologously expressed in Drosophila S3 cells with a biotinylated N-terminal tag, and then isolated from cell lysates with avidin beads. Purified, recombinant Asp1(371-920) contained iron and acid-labile sulfide, but the stoichiometry (0.8 atoms of each per protein molecule) indicates incomplete iron sulfur cluster assembly. We reconstituted the Fe-S cluster in vitro under anaerobic conditions, which increased the stoichiometry to approximately 2 atoms of iron and acid-labile sulfide per Asp1 molecule. The presence of a [2Fe-2S](2+) cluster in Asp1(371-920). was demonstrated by UV-visible absorption, resonance Raman spectroscopy, and electron paramagnetic resonance spectroscopy. We determined that this [2Fe-2S](2+) cluster is unlikely to participate in redox chemistry, since it rapidly degraded upon reduction by dithionite. Biochemical and mutagenic studies demonstrated that the [2Fe-2S](2+) cluster substantially inhibits the phosphatase activity of Asp1, thereby increasing its net kinase activity.
C1 [Wang, Huanchen; Nair, Vasudha S.; Shears, Stephen B.] NIEHS, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA.
[Holland, Ashley A.; Johnson, Michael K.] Univ Georgia, Dept Chem, Athens, GA 30602 USA.
[Holland, Ashley A.; Johnson, Michael K.] Univ Georgia, Ctr Metalloenzyme Studies, Athens, GA 30602 USA.
[Capolicchio, Sarnanta; Jessen, Henning J.] Univ Zurich UZH, Dept Chem, CH-8057 Zurich, Switzerland.
RP Shears, SB (reprint author), NIEHS, Lab Signal Transduct, NIH, 101 TW Alexander Dr, Res Triangle Pk, NC 27709 USA.
EM shears@niehs.nih.gov
RI Jessen, Henning/F-5108-2014
OI Jessen, Henning/0000-0002-1025-9484
FU NIH/National Institute of Environmental Health Sciences; National
Institutes of Health [GM62524]
FX This research was supported by the Intramural Research Program of the
NIH/National Institute of Environmental Health Sciences, and by a grant
from the National Institutes of Health (GM62524 to M.K.J.).
NR 69
TC 3
Z9 3
U1 1
U2 7
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 0006-2960
J9 BIOCHEMISTRY-US
JI Biochemistry
PD OCT 27
PY 2015
VL 54
IS 42
BP 6462
EP 6474
DI 10.1021/acs.biochem.5b00532
PG 13
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA CV0CY
UT WOS:000363916200006
PM 26422458
ER
PT J
AU Le, KY
Otto, M
AF Le, Katherine Y.
Otto, Michael
TI Quorum-sensing regulation in staphylococci-an overview
SO FRONTIERS IN MICROBIOLOGY
LA English
DT Review
DE Staphylococcus aureus; Staphylococcus epidermidis; quorum-sensing;
toxins; biofilm; Agr; LuxS
ID PHENOL-SOLUBLE MODULINS; AUREUS ALPHA-HEMOLYSIN; TO-CELL COMMUNICATION;
PROTEIN-A; VIRULENCE FACTORS; AUTOINDUCING PEPTIDE; BIOFILM MATURATION;
IN-VIVO; INFLAMMATORY RESPONSES; TRANSMEMBRANE TOPOLOGY
AB Staphylococci are frequent human commensals and some species can cause disease. Staphylococcus aureus in particular is a dangerous human pathogen. In staphylococci, the ability to sense the bacterial cell density, or quorum, and to respond with genetic adaptations is due to one main system, which is called accessory gene regulator (Agr). The extracellular signal of Agr is a post-translationally modified peptide containing a thiolactone structure. Under conditions of high cell density, Agr is responsible for the increased expression of many toxins and degradative exoenzymes, and decreased expression of several colonization factors. This regulation is important for the timing of virulence factor expression during infection and the development of acute disease, while low activity of Agr is associated with chronic staphylococcal infections, such as those involving biofilm formation. Accordingly, drugs inhibiting Agr are being evaluated for their capacity to control acute forms of S. aureus infection.
C1 [Le, Katherine Y.; Otto, Michael] NIAID, Pathogen Mol Genet Sect, Lab Bactenol, NIH, Bethesda, MD 20892 USA.
[Le, Katherine Y.] Mayo Clin, Coll Med, Dept Med, Div Hosp Internal Med, Rochester, MN USA.
RP Otto, M (reprint author), NIAID, Pathogen Mol Genet Sect, Lab Bactenol, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM motto@niaid.nih.gov
OI Otto, Michael/0000-0002-2222-4115
FU Intramural Research Program of the National Institute of Allergy and
Infectious Diseases, U.S. National Institutes of health [ZIA
AI000904-14]
FX This work was supported by the Intramural Research Program of the
National Institute of Allergy and Infectious Diseases, U.S. National
Institutes of health (grant ZIA AI000904-14).
NR 100
TC 10
Z9 10
U1 13
U2 63
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015,
SWITZERLAND
SN 1664-302X
J9 FRONT MICROBIOL
JI Front. Microbiol.
PD OCT 27
PY 2015
VL 6
AR 1174
DI 10.3389/fmicb.2015.01174
PG 8
WC Microbiology
SC Microbiology
GA CV3OL
UT WOS:000364168400001
PM 26579084
ER
PT J
AU Parra, M
Liu, X
Derrick, SC
Yang, A
Molina-Cruz, A
Barillas-Mury, C
Zheng, H
Pham, PT
Sedegah, M
Belmonte, A
Litilit, DD
Waldmann, TA
Kumar, S
Morris, SL
Perera, LP
AF Parra, Marcela
Liu, Xia
Derrick, Steven C.
Yang, Amy
Molina-Cruz, Alvaro
Barillas-Mury, Carolina
Zheng, Hong
Phuong Thao Pham
Sedegah, Martha
Belmonte, Arnel
Litilit, Dianne D.
Waldmann, Thomas A.
Kumar, Sanjai
Morris, Sheldon L.
Perera, Liyanage P.
TI Co-expression of Interleukin-15 Enhances the Protective Immune Responses
Induced by Immunization with a Murine Malaria MVA-Based Vaccine Encoding
the Circumsporozoite Protein
SO PLOS ONE
LA English
DT Article
AB Malaria remains a major global public health problem with an estimated 200 million cases detected in 2012. Although the most advanced candidate malaria vaccine (RTS,S) has shown promise in clinical trials, its modest efficacy and durability have created uncertainty about the impact of RTS, S immunization (when used alone) on global malaria transmission. Here we describe the development and characterization of a novel modified vaccinia virus Ankara (MVA)-based malaria vaccine which co-expresses the Plasmodium yoelii circumsporozoite protein (CSP) and IL-15. Vaccination/challenge studies showed that C57BL/6 mice immunized with the MVA-CSP/IL15 vaccine were protected significantly better against a P. yoelii 17XNL sporozoite challenge than either mice immunized with an MVA vaccine expressing only CSP or naive controls. Importantly, the levels of total anti-CSP IgG were elevated about 100-fold for the MVA-CSP/IL15 immunized group compared to mice immunized with the MVA-CSP construct that does not express IL-15. Among the IgG subtypes, the IL-15 expressing MVA-CSP vaccine induced levels of IgG1 (8 fold) and IgG2b (80 fold) higher than the MVA-CSP construct. The significantly enhanced humoral responses and protection detected after immunization with the MVA-CSP/IL-15 vaccine suggest that this IL-15 expressing MVA construct could be considered in the development of future malaria immunization strategies.
C1 [Parra, Marcela; Liu, Xia; Derrick, Steven C.; Yang, Amy; Zheng, Hong; Kumar, Sanjai; Morris, Sheldon L.] US FDA, Ctr Biol Evaluat & Res, Silver Spring, MD 20993 USA.
[Molina-Cruz, Alvaro; Barillas-Mury, Carolina] NIAID, Lab Malaria & Vector Res, Rockville, MD 20852 USA.
[Phuong Thao Pham; Sedegah, Martha; Belmonte, Arnel; Litilit, Dianne D.] Naval Med Res Ctr, Silver Spring, MD 20910 USA.
[Waldmann, Thomas A.; Perera, Liyanage P.] NCI, Bethesda, MD 20892 USA.
RP Perera, LP (reprint author), NCI, Bethesda, MD 20892 USA.
EM pereral@mail.nih.gov
FU Intramural Research Programs of the National Cancer Institute, Center
for Cancer Research, NIH; Food and Drug Administration
FX Funding was provided by the Intramural Research Programs of the National
Cancer Institute, Center for Cancer Research, NIH (T.A.W and L.P.P) and
the Food and Drug Administration. The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 0
TC 0
Z9 0
U1 1
U2 1
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD OCT 27
PY 2015
VL 10
IS 10
AR e0141141
DI 10.1371/journal.pone.0141141
PG 14
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CU8PC
UT WOS:000363804200032
PM 26505634
ER
PT J
AU Ocampo, J
Clark, DJ
AF Ocampo, Josefina
Clark, David J.
TI A Positive Twist to the Centromeric Nucleosome
SO CELL REPORTS
LA English
DT Editorial Material
ID BUDDING YEAST; CHROMATIN; DNA; ORGANIZATION; SCM3
C1 [Ocampo, Josefina; Clark, David J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Genom Differentiat, NIH, Bethesda, MD 20892 USA.
RP Clark, DJ (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Genom Differentiat, NIH, Bethesda, MD 20892 USA.
EM clarkda@mail.nih.gov
NR 10
TC 0
Z9 0
U1 0
U2 0
PU CELL PRESS
PI CAMBRIDGE
PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA
SN 2211-1247
J9 CELL REP
JI Cell Reports
PD OCT 27
PY 2015
VL 13
IS 4
BP 645
EP 646
DI 10.1016/j.celrep.2015.10.007
PG 2
WC Cell Biology
SC Cell Biology
GA CU8GY
UT WOS:000363780900001
PM 26510160
ER
PT J
AU Bhattacharyya, S
Gesteland, PH
Korgenski, K
Bjornstad, ON
Adler, FR
AF Bhattacharyya, Samit
Gesteland, Per H.
Korgenski, Kent
Bjornstad, Ottar N.
Adler, Frederick R.
TI Cross-immunity between strains explains the dynamical pattern of
paramyxoviruses
SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF
AMERICA
LA English
DT Article
DE paramyxoviruses; respiratory syncytial viruses; human parainfluenza;
pathogen interactions; cross-immunity
ID RESPIRATORY SYNCYTIAL VIRUS; PARAINFLUENZA VIRUS; TRANSMISSION DYNAMICS;
HOSPITAL ADMISSIONS; INFECTIOUS-DISEASES; CHILDHOOD DISEASES;
VIRAL-INFECTIONS; YOUNG-CHILDREN; AIR-POLLUTION; RSV INFECTION
AB Viral respiratory tract diseases pose serious public health problems. Our ability to predict and thus, be able to prepare for outbreaks is strained by the complex factors driving the prevalence and severity of these diseases. The abundance of diseases and transmission dynamics of strains are not only affected by external factors, such as weather, but also driven by interactions among viruses mediated by human behavior and immunity. To untangle the complex out-of-phase annual and biennial pattern of three common paramyxoviruses, Respiratory Syncytial Virus (RSV), Human Parainfluenza Virus (HPIV), and Human Metapneumovirus (hMPV), we adopt a theoretical approach that integrates ecological and immunological mechanisms of disease interactions. By estimating parameters from multiyear time series of laboratory-confirmed cases from the intermountain west region of the United States and using statistical inference, we show that models of immune-mediated interactions better explain the data than those based on ecological competition by convalescence. The strength of cross-protective immunity among viruses is correlated with their genetic distance in the phylogenetic tree of the paramyxovirus family.
C1 [Bhattacharyya, Samit; Bjornstad, Ottar N.] Penn State Univ, Ctr Infect Dis Dynam, University Pk, PA 16802 USA.
[Bhattacharyya, Samit; Adler, Frederick R.] Univ Utah, Dept Biol, Salt Lake City, UT 84112 USA.
[Gesteland, Per H.; Korgenski, Kent] Univ Utah, Sch Med, Dept Pediat, Salt Lake City, UT 84112 USA.
[Gesteland, Per H.] Univ Utah, Dept Biomed Informat, Salt Lake City, UT 84112 USA.
[Korgenski, Kent] Intermt Healthcare, Pediat Clin Program, Salt Lake City, UT 84111 USA.
[Bjornstad, Ottar N.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Adler, Frederick R.] Univ Utah, Dept Math, Salt Lake City, UT 84112 USA.
RP Bhattacharyya, S (reprint author), Penn State Univ, Ctr Infect Dis Dynam, University Pk, PA 16802 USA.
EM szb16@psu.edu
FU University of Utah Funding Incentive SEED Grant; Agency for Healthcare
Research and Quality Grant [K08 HS018538]; Bill and Melinda Gates
Foundation; Research and Policy for Infectious Disease Dynamics (RAPIDD)
Program of the Science and Technology Directorate; Department of
Homeland Security; Fogarty International Center, National Institutes of
Health; James S. McDonnell Foundation 21st Century Science Initiative
Grant
FX We thank Pejman Rohani and Sourya Shrestha (University of Michigan) for
fruitful discussion about the work and two anonymous reviewers for
useful comments to improve the analysis in the paper. This work was
supported by a University of Utah Funding Incentive SEED Grant; Agency
for Healthcare Research and Quality Grant K08 HS018538 (to P.H.G.); the
Bill and Melinda Gates Foundation (O.N.B.); the Research and Policy for
Infectious Disease Dynamics (RAPIDD) Program of the Science and
Technology Directorate; the Department of Homeland Security; the Fogarty
International Center, National Institutes of Health (O.N.B.); and James
S. McDonnell Foundation 21st Century Science Initiative Grant (to
F.R.A.).
NR 56
TC 2
Z9 2
U1 0
U2 2
PU NATL ACAD SCIENCES
PI WASHINGTON
PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA
SN 0027-8424
J9 P NATL ACAD SCI USA
JI Proc. Natl. Acad. Sci. U. S. A.
PD OCT 27
PY 2015
VL 112
IS 43
BP 13396
EP 13400
DI 10.1073/pnas.1516698112
PG 5
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CU3WY
UT WOS:000363458100073
PM 26460003
ER
PT J
AU Doyle, JJ
Doyle, AJ
Wilson, NK
Habashi, JP
Bedja, D
Whitworth, RE
Lindsay, ME
Schoenhoff, F
Myers, L
Huso, N
Bachir, S
Squires, O
Rusholme, B
Ehsan, H
Huso, D
Thomas, CJ
Caulfield, MJ
Van Eyk, JE
Judge, DP
Dietz, HC
AF Doyle, Jefferson J.
Doyle, Alexander J.
Wilson, Nicole K.
Habashi, Jennifer P.
Bedja, Djahida
Whitworth, Ryan E.
Lindsay, Mark E.
Schoenhoff, Florian
Myers, Loretha
Huso, Nick
Bachir, Suha
Squires, Oliver
Rusholme, Benjamin
Ehsan, Hamid
Huso, David
Thomas, Craig J.
Caulfield, Mark J.
Van Eyk, Jennifer E.
Judge, Daniel P.
Dietz, Harry C.
CA GenTAC Registry Consortium
MIBAVA Leducq Consortium
TI A deleterious gene-by-environment interaction imposed by calcium channel
blockers in Marfan syndrome
SO ELIFE
LA English
DT Article
ID KINASE-C-DELTA; AORTIC-ANEURYSM PROGRESSION; ANGIOTENSIN-II; MOUSE
MODEL; BETA; GROWTH; ACTIVATION; BLOCKADE; PATHWAY; CELLS
AB Calcium channel blockers (CCBs) are prescribed to patients with Marfan syndrome for prophylaxis against aortic aneurysm progression, despite limited evidence for their efficacy and safety in the disorder. Unexpectedly, Marfan mice treated with CCBs show accelerated aneurysm expansion, rupture, and premature lethality. This effect is both extracellular signal-regulated kinase (ERK1/2) dependent and angiotensin-II type 1 receptor (AT1R) dependent. We have identified protein kinase C beta (PKC beta) as a critical mediator of this pathway and demonstrate that the PKC beta inhibitor enzastaurin, and the clinically available anti-hypertensive agent hydralazine, both normalize aortic growth in Marfan mice, in association with reduced PKC beta and ERK1/2 activation. Furthermore, patients with Marfan syndrome and other forms of inherited thoracic aortic aneurysm taking CCBs display increased risk of aortic dissection and need for aortic surgery, compared to patients on other antihypertensive agents.
C1 [Doyle, Jefferson J.; Doyle, Alexander J.; Wilson, Nicole K.; Habashi, Jennifer P.; Myers, Loretha; Huso, Nick; Bachir, Suha; Squires, Oliver; Rusholme, Benjamin; Dietz, Harry C.] Johns Hopkins Univ, Sch Med, Howard Hughes Med Inst, Baltimore, MD 21205 USA.
[Doyle, Jefferson J.; Doyle, Alexander J.; Wilson, Nicole K.; Habashi, Jennifer P.; Myers, Loretha; Huso, Nick; Bachir, Suha; Squires, Oliver; Rusholme, Benjamin; Dietz, Harry C.] Johns Hopkins Univ, Sch Med, Inst Med Genet, Baltimore, MD USA.
[Doyle, Jefferson J.; Ehsan, Hamid] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21205 USA.
[Doyle, Alexander J.; Caulfield, Mark J.] Queen Mary Univ London, William Harvey Res Inst, Barts & London Sch Med, London, England.
[Habashi, Jennifer P.; Dietz, Harry C.] Johns Hopkins Univ, Sch Med, Dept Pediat, Div Pediat Cardiol, Baltimore, MD 21205 USA.
[Bedja, Djahida] Johns Hopkins Univ, Sch Med, Dept Cardiol, Baltimore, MD USA.
[Bedja, Djahida] Macquarie Univ, Australian Sch Adv Med, Sydney, NSW, Australia.
[Whitworth, Ryan E.] Res Triangle Inst Int, Durham, NC USA.
[Lindsay, Mark E.] Harvard Med Sch, Thorac Aort Ctr, Massachusetts Gen Hosp, Dept Med, Boston, MA USA.
[Lindsay, Mark E.] Harvard Med Sch, Thorac Aort Ctr, Massachusetts Gen Hosp, Dept Pediat, Boston, MA USA.
[Schoenhoff, Florian] Inselspital Bern, Dept Cardiovasc Surg, Bern, Switzerland.
[Schoenhoff, Florian; Van Eyk, Jennifer E.] Johns Hopkins Univ, Sch Med, Prote Innovat Ctr Heart Failure, Baltimore, MD USA.
[Huso, David] Johns Hopkins Univ, Sch Med, Dept Mol & Comparat Pathobiol, Baltimore, MD USA.
[Thomas, Craig J.] Natl Ctr Adv Translat Sci, Div Preclin Innovat, Bethesda, MD USA.
[Judge, Daniel P.; Dietz, Harry C.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA.
RP Doyle, JJ (reprint author), Johns Hopkins Univ, Sch Med, Howard Hughes Med Inst, Baltimore, MD 21205 USA.
EM doyle@jhmi.edu; hdietz@jhmi.edu
FU National Institutes of Health [AR041135, AR049698]; Howard Hughes
Medical Institute; National Marfan Foundation Bloomberg Fund; National
Marfan Foundation Smilow Center for Marfan Syndrome Research; Fondation
Leducq MIBAVA Leducq Consortium; National Heart, Lung, and Blood
Institute GenTAC Consortium
FX National Institutes of Health AR041135 Jennifer P Habashi, Harry C
Dietz; Howard Hughes Medical Institute Alexander J Doyle, Harry C Dietz;
National Marfan Foundation Bloomberg Fund Jefferson J Doyle, Jennifer P
Habashi, Harry C Dietz; National Marfan Foundation Smilow Center for
Marfan Syndrome Research Harry C Dietz; Fondation Leducq MIBAVA Leducq
Consortium MIBAVA Members; National Heart, Lung, and Blood Institute
GenTAC Consortium GenTAC Members; National Institute of Health AR049698
Jennifer P Habashi, Harry C Dietz
NR 36
TC 0
Z9 0
U1 0
U2 0
PU ELIFE SCIENCES PUBLICATIONS LTD
PI CAMBRIDGE
PA SHERATON HOUSE, CASTLE PARK, CAMBRIDGE, CB3 0AX, ENGLAND
SN 2050-084X
J9 ELIFE
JI eLife
PD OCT 27
PY 2015
VL 4
AR e08648
DI 10.7554/eLife.08648
PG 18
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA EJ7RE
UT WOS:000393419100001
ER
PT J
AU Doyle, JJ
Doyle, AJ
Wilson, NK
Habashi, JP
Bedja, D
Whitworth, RE
Lindsay, ME
Schoenhoff, F
Myers, L
Huso, N
Bachir, S
Squires, O
Rusholme, B
Ehsan, H
Huso, D
Thomas, CJ
Caulfield, MJ
Van Eyk, JE
Judge, DP
Dietz, HC
AF Doyle, Jefferson J.
Doyle, Alexander J.
Wilson, Nicole K.
Habashi, Jennifer P.
Bedja, Djahida
Whitworth, Ryan E.
Lindsay, Mark E.
Schoenhoff, Florian
Myers, Loretha
Huso, Nick
Bachir, Suha
Squires, Oliver
Rusholme, Benjamin
Ehsan, Hamid
Huso, David
Thomas, Craig J.
Caulfield, Mark J.
Van Eyk, Jennifer E.
Judge, Daniel P.
Dietz, Harry C.
CA GenTAC Registry Consortium
MIBAVA Leducq Consortium
TI A deleterious gene-by-environment interaction imposed by calcium channel
blockers in Marfan syndrome
SO ELIFE
LA English
DT Article
ID KINASE-C-DELTA; AORTIC-ANEURYSM PROGRESSION; ANGIOTENSIN-II; MOUSE
MODEL; GROWTH; ACTIVATION; BLOCKADE; PATHWAY; CELLS; MICE
AB Calcium channel blockers (CCBs) are prescribed to patients with Marfan syndrome for prophylaxis against aortic aneurysm progression, despite limited evidence for their efficacy and safety in the disorder. Unexpectedly, Marfan mice treated with CCBs show accelerated aneurysm expansion, rupture, and premature lethality. This effect is both extracellular signal-regulated kinase (ERK1/2) dependent and angiotensin-II type 1 receptor (AT1R) dependent. We have identified protein kinase C beta (PKC beta) as a critical mediator of this pathway and demonstrate that the PKC beta inhibitor enzastaurin, and the clinically available anti-hypertensive agent hydralazine, both normalize aortic growth in Marfan mice, in association with reduced PKCa and ERK1/2 activation. Furthermore, patients with Marfan syndrome and other forms of inherited thoracic aortic aneurysm taking CCBs display increased risk of aortic dissection and need for aortic surgery, compared to patients on other antihypertensive agents.
C1 [Doyle, Jefferson J.; Doyle, Alexander J.; Wilson, Nicole K.; Habashi, Jennifer P.; Myers, Loretha; Huso, Nick; Bachir, Suha; Squires, Oliver; Rusholme, Benjamin; Dietz, Harry C.] Johns Hopkins Univ, Sch Med, Howard Hughes Med Inst, Baltimore, MD 21205 USA.
[Doyle, Jefferson J.; Doyle, Alexander J.; Wilson, Nicole K.; Habashi, Jennifer P.; Myers, Loretha; Huso, Nick; Bachir, Suha; Squires, Oliver; Rusholme, Benjamin; Dietz, Harry C.] Johns Hopkins Univ, Sch Med, Inst Med Genet, Baltimore, MD USA.
[Doyle, Jefferson J.; Ehsan, Hamid] Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21205 USA.
[Doyle, Alexander J.; Caulfield, Mark J.] Queen Mary Univ London, Barts & London Sch Med, William Harvey Res Inst, London, England.
[Habashi, Jennifer P.; Dietz, Harry C.] Johns Hopkins Univ, Sch Med, Dept Pediat, Div Pediat Cardiol, Baltimore, MD 21205 USA.
[Bedja, Djahida] Johns Hopkins Univ, Sch Med, Dept Cardiol, Baltimore, MD USA.
[Bedja, Djahida] Macquarie Univ, Australian Sch Adv Med, Sydney, NSW 2109, Australia.
[Whitworth, Ryan E.] Res Triangle Inst Int, Durham, NC USA.
[Lindsay, Mark E.] Harvard Univ, Sch Med, Dept Med, Thorac Aort Ctr,Massachusetts Gen Hosp, Boston, MA USA.
[Lindsay, Mark E.] Harvard Univ, Sch Med, Dept Pediat, Thorac Aort Ctr,Massachusetts Gen Hosp, Boston, MA 02115 USA.
[Schoenhoff, Florian] Univ Bern, Inselspital, Dept Cardiovasc Surg, CH-3010 Bern, Switzerland.
[Schoenhoff, Florian; Van Eyk, Jennifer E.] Johns Hopkins Univ, Sch Med, Prote Innovat Ctr Heart Failure, Baltimore, MD USA.
[Huso, David] Johns Hopkins Univ, Sch Med, Dept Mol & Comparat Pathobiol, Baltimore, MD USA.
[Thomas, Craig J.] Natl Ctr Adv Translat Sci, Div Preclin Innovat, Bethesda, MD USA.
[Judge, Daniel P.; Dietz, Harry C.] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA.
RP Doyle, JJ (reprint author), Johns Hopkins Univ, Sch Med, Howard Hughes Med Inst, Baltimore, MD 21205 USA.
EM jefferson.doyle@jhmi.edu; hdietz@jhmi.edu
FU National Institutes of Health [AR041135, AR049698]; Howard Hughes
Medical Institute; National Marfan Foundation; Fondation Leducq MIBAVA
Leducq Consortium; National Heart, Lung, and Blood Institute GenTAC
Consortium
FX National Institutes of Health AR041135 Jennifer P Habashi, Harry C
Dietz; Howard Hughes Medical Institute Alexander J Doyle, Harry C Dietz;
National Marfan Foundation Bloomberg Fund Jefferson J Doyle, Jennifer P
Habashi, Harry C Dietz; National Marfan Foundation Smilow Center for
Marfan Syndrome Research Harry C Dietz; Fondation Leducq MIBAVA Leducq
Consortium MIBAVA Members; National Heart, Lung, and Blood Institute
GenTAC Consortium GenTAC Members; National Institute of Health AR049698
Jennifer P Habashi, Harry C Dietz
NR 36
TC 10
Z9 10
U1 0
U2 3
PU ELIFE SCIENCES PUBLICATIONS LTD
PI CAMBRIDGE
PA SHERATON HOUSE, CASTLE PARK, CAMBRIDGE, CB3 0AX, ENGLAND
SN 2050-084X
J9 ELIFE
JI eLife
PD OCT 27
PY 2015
VL 4
AR e08648
DI 10.7554/eLife.08648
PG 18
WC Biology
SC Life Sciences & Biomedicine - Other Topics
GA CU8MS
UT WOS:000363797700001
ER
PT J
AU Chen, G
Saad, ZS
Adleman, NE
Leibenluft, E
Cox, RW
AF Chen, Gang
Saad, Ziad S.
Adleman, Nancy E.
Leibenluft, Ellen
Cox, Robert W.
TI Detecting the subtle shape differences in hemodynamic responses at the
group level
SO FRONTIERS IN NEUROSCIENCE
LA English
DT Article
DE hemodynamic response; basis function; multivariate general linear model;
linear mixed-effects model; FMRI group analysis; AFNI
ID GENERAL LINEAR-MODEL; FMRI GROUP-ANALYSIS; MULTI-SUBJECT FMRI;
EVENT-RELATED FMRI; STATISTICAL-ANALYSIS; BOLD SIGNAL; BRAIN;
ACTIVATION; INFERENCE; HIPPOCAMPAL
AB The nature of the hemodynamic response (HDR) is still not fully understood due to the multifaceted processes involved. Aside from the overall amplitude, the response may vary across cognitive states, tasks, brain regions, and subjects with respect to characteristics such as rise and fall speed, peak duration, undershoot shape, and overall duration. Here we demonstrate that the fixed-shape (FSM) or adjusted-shape (ASM) methods may fail to detect some shape subtleties (e.g., speed of rise or recovery, or undershoot). In contrast, the estimated-shape method (ESM) through multiple basis functions can provide the opportunity to identify some subtle shape differences and achieve higher statistical power at both individual and group levels. Previously, some dimension reduction approaches focused on the peak magnitude, or made inferences based on the area under the curve (AUC) or interaction, which can lead to potential misidentifications. By adopting a generic framework of multivariate modeling (MVM), we showcase a hybrid approach that is validated by simulations and real data. With the whole HDR shape integrity maintained as input at the group level, the approach allows the investigator to substantiate these more nuanced effects through the unique HDR shape features. Unlike the few analyses that were limited to main effect, two- or three-way interactions, we extend the modeling approach to an inclusive platform that is more adaptable than the conventional GLM. With multiple effect estimates from ESM for each condition, linear mixed-effects (LME) modeling should be used at the group level when there is only one group of subjects without any other explanatory variables. Under other situations, an approximate approach through dimension reduction within the MVM framework can be adopted to achieve a practical equipoise among representation, false positive control, statistical power, and modeling flexibility. The associated program 3 dMVM is publicly available as part of the AFNI suite.
C1 [Chen, Gang; Saad, Ziad S.; Cox, Robert W.] NIMH, Sci & Stat Comp Core, NIH, US Dept HHS, Bethesda, MD 20892 USA.
[Adleman, Nancy E.] Catholic Univ Amer, Dept Psychol, Washington, DC 20064 USA.
[Leibenluft, Ellen] NIMH, Sect Bipolar Spectrum Disorders, Emot & Dev Branch, NIH,US Dept HHS, Bethesda, MD 20892 USA.
RP Chen, G (reprint author), NIMH, Sci & Stat Comp Core, NIH, US Dept HHS, Bethesda, MD 20892 USA.
EM gangchen@mail.nih.gov
FU NIMH; NINDS intramural Research Programs of the NIH/HHS, USA
FX Our work benefited significantly from the statistical computational
language and environment R, its many packages, and the great support of
the R community. All the plots were created in R with the base graphics
library. Special thanks are due to Helios de Rosario for his help in
technical details of using the R package phia. The research and writing
of the paper were supported by the NIMH and NINDS intramural Research
Programs of the NIH/HHS, USA.
NR 63
TC 1
Z9 1
U1 4
U2 4
PU FRONTIERS MEDIA SA
PI LAUSANNE
PA PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015,
SWITZERLAND
SN 1662-453X
J9 FRONT NEUROSCI-SWITZ
JI Front. Neurosci.
PD OCT 26
PY 2015
VL 9
AR 375
DI 10.3389/fnins.2015.00375
PG 18
WC Neurosciences
SC Neurosciences & Neurology
GA CY9EV
UT WOS:000366711100001
PM 26578853
ER
PT J
AU Taraska, JW
AF Taraska, Justin W.
TI Cell biology of the future: Nanometer-scale cellular cartography
SO JOURNAL OF CELL BIOLOGY
LA English
DT Editorial Material
ID ELECTRON-MICROSCOPY; SUPERRESOLUTION FLUORESCENCE; LOCALIZATION;
ENDOCYTOSIS; TOMOGRAPHY; PROTEINS; DYNAMICS; YEAST
AB Understanding cellular structure is key to understanding cellular regulation. New developments in super-resolution fluorescence imaging, electron microscopy, and quantitative image analysis methods are now providing some of the first three-dimensional dynamic maps of biomolecules at the nanometer scale. These new maps-comprehensive nanometer-scale cellular cartographies-will reveal how the molecular organization of cells influences their diverse and changeable activities.
C1 NHLBI, Biochem & Biophys Ctr, NIH, Bethesda, MD 20892 USA.
RP Taraska, JW (reprint author), NHLBI, Biochem & Biophys Ctr, NIH, Bethesda, MD 20892 USA.
EM justin.taraska@nih.gov
RI Taraska, Justin/H-8876-2016
OI Taraska, Justin/0000-0001-5355-9535
FU Intramural NIH HHS
NR 24
TC 0
Z9 0
U1 1
U2 13
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 950 THIRD AVE, 2ND FLR, NEW YORK, NY 10022 USA
SN 0021-9525
EI 1540-8140
J9 J CELL BIOL
JI J. Cell Biol.
PD OCT 26
PY 2015
VL 211
IS 2
BP 211
EP 214
DI 10.1083/jcb.201508021
PG 4
WC Cell Biology
SC Cell Biology
GA CV4XN
UT WOS:000364269900003
PM 26483557
ER
PT J
AU Choudhary, V
Ojha, N
Golden, A
Prinz, WA
AF Choudhary, Vineet
Ojha, Namrata
Golden, Andy
Prinz, William A.
TI A conserved family of proteins facilitates nascent lipid droplet budding
from the ER
SO JOURNAL OF CELL BIOLOGY
LA English
DT Article
ID YEAST SACCHAROMYCES-CEREVISIAE; PRESSURE FROZEN SAMPLES;
ENDOPLASMIC-RETICULUM; FAT STORAGE; CAENORHABDITIS-ELEGANS;
TRANSMEMBRANE PROTEIN-2; ELECTRON-MICROSCOPY; BODY FORMATION;
BIOGENESIS; SEIPIN
AB Lipid droplets (LDs) are found in all cells and play critical roles in lipid metabolism. De novo LD biogenesis occurs in the endoplasmic reticulum (ER) but is not well understood. We imaged early stages of LD biogenesis using electron microscopy and found that nascent LDs form lens-like structures that are in the ER membrane, raising the question of how these nascent LDs bud from the ER as they grow. We found that a conserved family of proteins, fat storage-inducing transmembrane (FIT) proteins, is required for proper budding of LDs from the ER. Elimination or reduction of FIT proteins in yeast and higher eukaryotes causes LDs to remain in the ER membrane. Deletion of the single FIT protein in Caenorhabditis elegans is lethal, suggesting that LD budding is an essential process in this organism. Our findings indicated that FIT proteins are necessary to promote budding of nascent LDs from the ER.
C1 [Choudhary, Vineet; Ojha, Namrata; Prinz, William A.] NIDDK, Mol Cell Biol Lab, NIH, Bethesda, MD 20892 USA.
[Golden, Andy] NIDDK, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA.
RP Prinz, WA (reprint author), NIDDK, Mol Cell Biol Lab, NIH, Bethesda, MD 20892 USA.
EM prinzw@helix.nih.gov
FU Intramural Research Program of the National Institute of Diabetes and
Digestive and Kidney Diseases; Swiss National Science Foundation
[PA00P3_145358, P300P3_158454]
FX This work was supported by the Intramural Research Program of the
National Institute of Diabetes and Digestive and Kidney Diseases. V.
Choudhary is supported by fellowship from Swiss National Science
Foundation (grants PA00P3_145358 and P300P3_158454).
NR 67
TC 13
Z9 13
U1 7
U2 17
PU ROCKEFELLER UNIV PRESS
PI NEW YORK
PA 950 THIRD AVE, 2ND FLR, NEW YORK, NY 10022 USA
SN 0021-9525
EI 1540-8140
J9 J CELL BIOL
JI J. Cell Biol.
PD OCT 26
PY 2015
VL 211
IS 2
BP 261
EP 271
DI 10.1083/jcb.201505067
PG 11
WC Cell Biology
SC Cell Biology
GA CV4XN
UT WOS:000364269900009
PM 26504167
ER
PT J
AU Colineau, L
Rouers, A
Yamamoto, T
Xu, Y
Urrutia, A
Pham, HP
Cardinaud, S
Samri, A
Dorgham, K
Coulon, PG
Cheynier, R
Hosmalin, A
Oksenhendler, E
Six, A
Kelleher, AD
Zaunders, J
Koup, RA
Autran, B
Moris, A
Graff-Dubois, S
AF Colineau, Lucie
Rouers, Angeline
Yamamoto, Takuya
Xu, Yin
Urrutia, Alejandra
Hang-Phuong Pham
Cardinaud, Sylvain
Samri, Assia
Dorgham, Karim
Coulon, Pierre-Gregoire
Cheynier, Remi
Hosmalin, Anne
Oksenhendler, Eric
Six, Adrien
Kelleher, Anthony D.
Zaunders, John
Koup, Richard A.
Autran, Brigitte
Moris, Arnaud
Graff-Dubois, Stephanie
TI HIV-Infected Spleens Present Altered Follicular Helper T Cell (Tfh)
Subsets and Skewed B Cell Maturation
SO PLOS ONE
LA English
DT Article
ID GERMINAL CENTER REACTIONS; IMMUNE THROMBOCYTOPENIA; UP-REGULATION;
REGULATORY CELLS; DENDRITIC CELLS; CENTER RESPONSE; LYMPH-NODES; CD40
LIGAND; WHITE PULPS; IN-VIVO
AB Follicular helper T (Tfh) cells within secondary lymphoid organs control multiple steps of B cell maturation and antibody (Ab) production. HIV-1 infection is associated with an altered B cell differentiation and Tfh isolated from lymph nodes of HIV-infected (HIV+) individuals provide inadequate B cell help in vitro. However, the mechanisms underlying this impairment of Tfh function are not fully defined. Using a unique collection of splenocytes, we compared the frequency, phenotype and transcriptome of Tfh subsets in spleens from HIV negative (HIV-) and HIV+ subjects. We observed an increase of CXCR5(+)PD-1(high)CD57-Tfh and germinal center (GC) CD57+ Tfh in HIV+ spleens. Both subsets showed a reduced mRNA expression of the transcription factor STAT-3, co-stimulatory, regulatory and signal transduction molecules as compared to HIV-spleens. Similarly, Foxp3 expressing follicular regulatory T (Tfr) cells were increased, suggesting sustained GC reactions in chronically HIV+ spleens. As a consequence, GC B cell populations were expanded, however, complete maturation into memory B cells was reduced in HIV+ spleens where we evidenced a compromised production of B cell-activating cytokines such as IL-4 and IL-10. Collectively our data indicate that, although Tfh proliferation and GC reactions seem to be ongoing in HIV-infected spleens, Tfh "differentiation" and expression of costimulatory molecules is skewed with a profound effect on B cell maturation.
C1 [Colineau, Lucie; Rouers, Angeline; Urrutia, Alejandra; Cardinaud, Sylvain; Samri, Assia; Dorgham, Karim; Coulon, Pierre-Gregoire; Autran, Brigitte; Moris, Arnaud; Graff-Dubois, Stephanie] Univ Paris 06, Sorbonne Univ, Ctr Immunol & Microbial Infect CIMI Paris, Paris, France.
[Colineau, Lucie; Rouers, Angeline; Urrutia, Alejandra; Cardinaud, Sylvain; Samri, Assia; Dorgham, Karim; Coulon, Pierre-Gregoire; Autran, Brigitte; Moris, Arnaud; Graff-Dubois, Stephanie] INSERM, U1135, Ctr Immunol & Microbial Infect CIMI Paris, Paris, France.
[Colineau, Lucie; Rouers, Angeline; Urrutia, Alejandra; Cardinaud, Sylvain; Coulon, Pierre-Gregoire; Moris, Arnaud; Graff-Dubois, Stephanie] CNRS, ERL 8255, Ctr Immunol & Microbial Infect CIMI Paris, Paris, France.
[Yamamoto, Takuya; Koup, Richard A.] NIAID, Immunol Lab, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Xu, Yin; Kelleher, Anthony D.] Univ New S Wales, Kirby Inst Infect & Immun Soc, Sydney, NSW, Australia.
[Hang-Phuong Pham; Six, Adrien] Univ Paris 06, Sorbonne Univ, UMRS 959, Immunol Immunopathol Imunotherapy I3, Paris, France.
[Hang-Phuong Pham; Six, Adrien] INSERM, UMRS 959, Immunol Immunopathol Immunotherapy I3, Paris, France.
[Hang-Phuong Pham; Six, Adrien] CNRS, FRE3632, Immunol Immunopathol Immunotherapy I3, Paris, France.
[Cheynier, Remi; Hosmalin, Anne] Inst Cochin, INSERM, U1016, Paris, France.
[Cheynier, Remi; Hosmalin, Anne] CNRS, UMR8104, Paris, France.
[Cheynier, Remi; Hosmalin, Anne] Univ Paris 05, Sorbonne Paris Cite, Paris, France.
[Hosmalin, Anne] Hop Cochin, AP HP, F-75674 Paris, France.
[Oksenhendler, Eric] Univ Paris Diderot, Hop St Louis, AP HP, Dept Clin Immunol, Paris, France.
[Zaunders, John] St Vincents Hosp, St Vincents Ctr Appl Med Res, Sydney, NSW 2010, Australia.
[Samri, Assia; Dorgham, Karim; Autran, Brigitte; Moris, Arnaud] Hop La Pitie Salpetriere, AP HP, Dept Immunol, Paris, France.
RP Graff-Dubois, S (reprint author), Univ Paris 06, Sorbonne Univ, Ctr Immunol & Microbial Infect CIMI Paris, Paris, France.
EM stephanie.graff-dubois@upmc.fr
RI Cheynier, Remi/E-9921-2010;
OI Cheynier, Remi/0000-0003-1146-660X; dorgham, karim/0000-0001-9539-3203;
Moris, Arnaud/0000-0002-5052-1678; Yamamoto, Takuya/0000-0003-3753-1211
FU Agence Nationale de Recherche sur le SIDA et les hepatites virales
(ANRS); INSERMFrench government's [ANR-10-LABX-62-IBEID]; French
government; CutHIVac European consortium EU-FP7; LabEx Transimmunom
[ANR-11-IDEX-0004-02]; ANRS; Sidaction
FX This work was supported by the Agence Nationale de Recherche sur le SIDA
et les hepatites virales (ANRS) and INSERM, by the French government's
"Investissement d'Avenir" Program, Laboratoire d'excellence "Integrative
Biology of Emerging Infectious Diseases" (ANR-10-LABX-62-IBEID) and by
the CutHIVac European consortium EU-FP7. A. Six and HPP contribution was
partially sponsored by the LabEx Transimmunom (ANR-11-IDEX-0004-02). S.
Cardinaud was supported by ANRS and Sidaction. A. Urrutia was supported
by Sidaction. The funders had no role in study design, data collection
and analysis, decision to publish, or preparation of the manuscript.
NR 66
TC 7
Z9 7
U1 1
U2 6
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD OCT 26
PY 2015
VL 10
IS 10
AR e0140978
DI 10.1371/journal.pone.0140978
PG 19
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA CU8NN
UT WOS:000363799900019
PM 26501424
ER
EF