FN Thomson Reuters Web of Science™
VR 1.0
PT J
AU Chen, HL
Burton, EA
Ross, GW
Huang, XM
Savica, R
Abbott, RD
Ascherio, A
Caviness, JN
Gao, X
Gray, KA
Hong, JS
Kamel, F
Jennings, D
Kirshner, A
Lawler, C
Liu, R
Miller, GW
Nussbaum, R
Peddada, SD
Rick, AC
Ritz, B
Siderowf, AD
Tanner, CM
Troster, AI
Zhang, J
AF Chen, Honglei
Burton, Edward A.
Ross, G. Webster
Huang, Xuemei
Savica, Rodolfo
Abbott, Robert D.
Ascherio, Alberto
Caviness, John N.
Gao, Xiang
Gray, Kimberly A.
Hong, Jau-Shyong
Kamel, Freya
Jennings, Danna
Kirshner, Annette
Lawler, Cindy
Liu, Rui
Miller, Gary W.
Nussbaum, Robert
Peddada, Shyamal D.
Rick, Amy Comstock
Ritz, Beate
Siderowf, Andrew D.
Tanner, Caroline M.
Troester, Alexander I.
Zhang, Jing
TI Research on the Premotor Symptoms of Parkinson's Disease: Clinical and
Etiological Implications
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Review
ID SLEEP BEHAVIOR DISORDER; HUMAN ALPHA-SYNUCLEIN; BOWEL MOVEMENT
FREQUENCY; INCIDENTAL LEWY BODIES; CENTRAL-NERVOUS-SYSTEM; LRRK2 G2019S
MUTATION; H5N1 INFLUENZA-VIRUS; OLFACTORY DYSFUNCTION; RISK-FACTORS;
MOUSE MODEL
AB BACKGROUND: The etiology and natural history of Parkinson's disease (PD) are not well understood. Some non-motor symptoms such as hyposmia, rapid eye movement sleep behavior disorder, and constipation may develop during the prodromal stage of PD and precede PD diagnosis by years.
OBJECTIVES: We examined the promise and pitfalls of research on premotor symptoms of PD and developed priorities and strategies to understand their clinical and etiological implications.
METHODS: This review was based on a workshop, Parkinson's Disease Premotor Symptom Symposium, held 7-8 June 2012 at the National Institute of Environmental Health Sciences in Research Triangle Park, North Carolina.
DISCUSSION: Research on premotor symptoms of PD may offer an excellent opportunity to characterize high-risk populations and to better understand PD etiology. Such research may lead to evaluation of novel etiological hypotheses such as the possibility that environmental toxicants or viruses may initiate PD pathogenesis in the gastrointestinal tract or olfactory bulb. At present, our understanding of premotor symptoms of PD is in its infancy and faces many obstacles. These symptoms are often not specific to PD and have low positive predictive value for early PD diagnosis. Further, the pathological bases and biological mechanisms of these premotor symptoms and their relevance to PD pathogenesis are poorly understood.
CONCLUSION: This is an emerging research area with important data gaps to be filled. Future research is needed to understand the prevalence of multiple premotor symptoms and their etiological relevance to PD. Animal experiments and mechanistic studies will further understanding of the biology of these premotor symptoms and test novel etiological hypothesis.
C1 [Chen, Honglei; Gray, Kimberly A.; Hong, Jau-Shyong; Kamel, Freya; Kirshner, Annette; Lawler, Cindy; Liu, Rui; Peddada, Shyamal D.] NIEHS, NIH, US Dept HHS, Res Triangle Pk, NC 27709 USA.
[Burton, Edward A.] Univ Pittsburgh, Pittsburgh Inst Neurodegenerat Dis, Pittsburgh, PA USA.
[Ross, G. Webster] Vet Affairs Pacific Isl Hlth Care Syst, Honolulu, HI USA.
[Huang, Xuemei] Penn State Univ, Milton S Hershey Med Ctr, Hershey, PA 17033 USA.
[Savica, Rodolfo] Mayo Clin, Rochester, MN USA.
[Abbott, Robert D.] Univ Virginia, Sch Med, Charlottesville, VA 22908 USA.
[Ascherio, Alberto; Gao, Xiang] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
[Caviness, John N.] Mayo Clin Arizona, Scottsdale, AZ USA.
[Jennings, Danna] Inst Neurodegenerat Disorders, New Haven, CT USA.
[Miller, Gary W.] Emory Univ, Atlanta, GA 30322 USA.
[Nussbaum, Robert] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA.
[Rick, Amy Comstock] Parkinsons Act Network, Washington, DC USA.
[Ritz, Beate] Univ Calif Los Angeles, Los Angeles, CA USA.
[Siderowf, Andrew D.] Avid Radiopharmaceut, Philadelphia, PA USA.
[Tanner, Caroline M.] Parkinson Inst, Sunnyvale, CA USA.
[Tanner, Caroline M.] Stanford Univ, Sch Med, Dept Hlth Res & Policy, Stanford, CA 94305 USA.
[Troester, Alexander I.] Barrow Neurol Inst, Phoenix, AZ 85013 USA.
[Zhang, Jing] Univ Washington, Seattle, WA 98195 USA.
RP Chen, HL (reprint author), NIEHS, Epidemiol Branch, 111 TW Alexander Dr,POB 12233,Mail Drop A3-05, Res Triangle Pk, NC 27709 USA.
EM chenh2@niehs.nih.gov
RI Gray, Kimberly/B-6989-2009; Ritz, Beate/E-3043-2015;
OI Kamel, Freya/0000-0001-5052-6615; Chen, Honglei/0000-0003-3446-7779
FU National Institute of Environmental Health Sciences; Complete Genomics
Inc.; Michael J. Fox Foundation; Brin Foundation; Parkinson's Institute
and Clinical Center; Parkinson's Disease Foundation; U.S. Army Medical
Research Acquisition Activity (the Telemedicine & Advanced Technology
Research Center-managed Neurotoxin Exposure Treatment Research Program);
National Institutes of Health, National Institute of Neurological
Disorders and Stroke
FX The Parkinson's Disease Premotor Symptom Symposium was jointly supported
by the intramural and extramural research programs of the National
Institute of Environmental Health Sciences. We thank M. Watson and K.
Gillig for their help in organizing the meeting and E. J. Zhao and E.
Hood for their help in preparing this manuscript.; X. G. has a
consultancy relationship with Teva; R.N. was a paid consultant for
Complete Genomics Inc.; A. C. R is an employee of the Parkinson Action
Network; and A. D. S. is an employee of Avid Radiopharmaceuticals Inc.
C. M. T. is an employee of the Parkinson's Institute. She serves on the
Scientific Advisory Boards of the Michael J. Fox Foundation and the
National Spasmodic Dystonia Association and has provided consulting
services to Impax Pharmaceuticals, Adamas Pharmaceuticals, and Abbvie
Pharmaceuticals. She also receives grant support from the Michael J. Fox
Foundation, the Brin Foundation, James and Sharron Clark, the
Parkinson's Institute and Clinical Center, the Parkinson's Disease
Foundation, the U.S. Army Medical Research Acquisition Activity (the
Telemedicine & Advanced Technology Research Center-managed Neurotoxin
Exposure Treatment Research Program), and the National Institutes of
Health, National Institute of Neurological Disorders and Stroke. A. I. T
is a consultant and/or speaker for Medtronic, St. Jude Medical, and
Boston Scientific. The other authors declare they have no actual or -
potential competing financial interests.
NR 99
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U1 0
U2 19
PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE
PI RES TRIANGLE PK
PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233,
RES TRIANGLE PK, NC 27709-2233 USA
SN 0091-6765
EI 1552-9924
J9 ENVIRON HEALTH PERSP
JI Environ. Health Perspect.
PD NOV-DEC
PY 2013
VL 121
IS 11-12
BP 1245
EP 1252
DI 10.1289/ehp.1306967
PG 8
WC Environmental Sciences; Public, Environmental & Occupational Health;
Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Toxicology
GA 266ZA
UT WOS:000328061900012
PM 23933572
ER
PT J
AU Lam, T
Williams, PL
Burns, JS
Sergeyev, O
Korrick, SA
Lee, MM
Birnbaum, LS
Revich, B
Altshul, LM
Patterson, DG
Turner, WE
Hauser, R
AF Lam, Thuy
Williams, Paige L.
Burns, Jane S.
Sergeyev, Oleg
Korrick, Susan A.
Lee, Mary M.
Birnbaum, Linda S.
Revich, Boris
Altshul, Larisa M.
Patterson, Donald G., Jr.
Turner, Wayman E.
Hauser, Russ
TI Predictors of Serum Chlorinated Pesticide Concentrations among
Prepubertal Russian Boys
SO ENVIRONMENTAL HEALTH PERSPECTIVES
LA English
DT Article
ID PERSISTENT ORGANIC POLLUTANTS; SCHOOL-AGED CHILDREN;
POLYCHLORINATED-BIPHENYLS; ORGANOCHLORINE PESTICIDES; DIOXIN EXPOSURE;
ADIPOSE-TISSUE; DIETARY-INTAKE; LIFE-STYLE; HEXACHLOROBENZENE;
HEXACHLOROCYCLOHEXANE
AB BACKGROUND: Few studies have evaluated predictors of childhood exposure to organochlorine pesticides (OCPs), a class of lipophilic persistent chemicals. Objectives: Our goal was to identify predictors of serum OCP concentrations-hexachlorobenzene (HCB), beta-hexachlorocyclohexane (beta-HCH), and p,p-dichlorodiphenyldichloroethylene (p,p'-DDE)-among boys in Chapaevsk, Russia.
METHODS: Between 2003 and 2005, 499 boys 8-9 years of age were recruited in a prospective cohort. The initial study visit included a physical examination; blood collection; health, lifestyle, and food-frequency questionnaires; and determination of residential distance from a local factory complex that produced HCB and beta-HCH. Fasting serum samples were analyzed for OCPs at the U.S. Centers for Disease Control and Prevention. General linear regression models were used to identify predictors of the boys' serum HCB, beta-HCH, and p,p'-DDE concentrations.
RESULTS: Among 355 boys with OCP measurements, median serum HCB, beta-HCH, and p,p'-DDE concentrations were 158, 167, and 284 ng/g lipid, respectively. Lower body mass index, longer breastfeeding duration, and local dairy consumption were associated with higher concentrations of OCPs. Boys who lived < 2 km from the factory complex had 64% (95% CI: 37, 96) and 57% (95% CI: 32, 87) higher mean HCB and beta-HCH concentrations, respectively, than boys who lived >= 5 km away. Living > 3 years in Chapaevsk predicted higher beta-HCH concentrations, and having parents who lacked a high school education predicted higher p,p'-DDE concentrations.
CONCLUSIONS: Among this cohort of prepubertal Russian boys, predictors of serum OCPs included consumption of local dairy products, longer local residence, and residential proximity to the local factory complex.
C1 [Lam, Thuy; Burns, Jane S.; Korrick, Susan A.; Hauser, Russ] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Environm & Occupat Med & Epidemiol Program, Boston, MA 02115 USA.
[Williams, Paige L.] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Sergeyev, Oleg] Samara State Med Univ, Dept Phys Educ & Hlth, Samara, Russia.
[Sergeyev, Oleg] Chapaevsk Med Assoc, Chapaevsk, Samara Region, Russia.
[Korrick, Susan A.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Div Network Med,Dept Med, Boston, MA 02115 USA.
[Lee, Mary M.] Univ Massachusetts, Sch Med, Dept Pediat & Cell Biol, Pediat Endocrine Div, Worcester, MA USA.
[Birnbaum, Linda S.] NCI, Res Triangle Pk, NC USA.
[Birnbaum, Linda S.] NIEHS, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
[Revich, Boris] Russian Acad Sci, Inst Forecasting, Moscow, Russia.
[Altshul, Larisa M.] Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Exposure Epidemiol & Risk Program, Boston, MA 02115 USA.
[Altshul, Larisa M.] Environm Hlth & Engn Inc, Needham, MA USA.
[Patterson, Donald G., Jr.] EnviroSolut Consulting Inc, Auburn, GA USA.
[Patterson, Donald G., Jr.] Axys Analyt Solut, Sidney, BC, Canada.
[Patterson, Donald G., Jr.] Exponent Inc, Maynard, MA USA.
[Turner, Wayman E.] Ctr Dis Control & Prevent, Atlanta, GA USA.
RP Lam, T (reprint author), Environm & Occupat Med & Epidemiol Program, 665 Huntington Ave,Bldg 1,Room 1406N, Boston, MA 02115 USA.
EM tlam@mail.harvard.edu; rhauser@hsph.harvard.edu
RI Sergeyev, Oleg/H-8854-2013
OI Sergeyev, Oleg/0000-0002-5745-3348
FU U.S. Environmental Protection Agency [R82943701]; National Institute of
Environmental Health Sciences [ES014370, ES000002, ES017117]; National
Institute for Occupational Safety and Health [T42-OH008416-04]
FX This work was funded by the U.S. Environmental Protection Agency
(R82943701) and the National Institute of Environmental Health Sciences
(ES014370, ES000002, and ES017117). T. L. is supported by National
Institute for Occupational Safety and Health training grant
T42-OH008416-04.
NR 45
TC 6
Z9 6
U1 3
U2 12
PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE
PI RES TRIANGLE PK
PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233,
RES TRIANGLE PK, NC 27709-2233 USA
SN 0091-6765
EI 1552-9924
J9 ENVIRON HEALTH PERSP
JI Environ. Health Perspect.
PD NOV-DEC
PY 2013
VL 121
IS 11-12
BP 1372
EP 1377
DI 10.1289/ehp.1306480
PG 6
WC Environmental Sciences; Public, Environmental & Occupational Health;
Toxicology
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Toxicology
GA 266ZA
UT WOS:000328061900028
PM 23955839
ER
PT J
AU Piao, YS
Wiesenfeld, P
Sprando, R
Arnold, JT
AF Piao, Yun-shang
Wiesenfeld, Paddy
Sprando, Robert
Arnold, Julia T.
TI TGF beta 1 alters androgenic metabolites and hydroxysteroid
dehydrogenase enzyme expression in human prostate reactive stromal
primary cells: Is steroid metabolism altered by prostate reactive
stromal microenvironment?
SO JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY
LA English
DT Article
DE TGF beta 1; Reactive prostate stroma; Androstenedione; Testosterone;
DHEA; Steroid metabolism
ID TRANSFORMING-GROWTH-FACTOR; 3-BETA-HYDROXYSTEROID DEHYDROGENASE; 5
17-BETA-HYDROXYSTEROID-DEHYDROGENASE; FACTOR-BETA; ESTROGEN METABOLISM;
EPITHELIAL-CELLS; CANCER; TYPE-2; DHEA; GROWTH-FACTOR-BETA-1
AB The inflammatory tissue microenvironment can be an active promoter in preneoplastic cancer lesions. Altered steroid hormone metabolism as induced by the inflammatory microenvironment may contribute to epithelial cancer progression. Dehydroepiandrosterone sulfate (DHEAS) is the most abundant endogenous steroid hormone present in human serum and can be metabolized to DHEA, androgens and/or estrogens in peripheral tissues. We have previously reported that TGF beta 1-induced reactive prostate stromal cells increase DHEA metabolism to active androgens and alter prostate cancer cell gene expression. While much of the focus on mechanisms of prostate cancer and steroid metabolism is in the epithelial cancer cells, this study focuses on TGF beta 1-induced effects on DHEA metabolic pathways and enzymes in human prostate stromal cells. In DHEA-treated primary prostate stromal cells, TGF beta 1 produced time-and dose-dependent increases in metabolism of DHEA to androstenedione and testosterone. Also TGF beta 1-treated prostate stromal cells exhibited changes in the gene expression of enzymes involved in steroid metabolism including up-regulation of 3 beta hydroxysteroid dehydrogenase (HSD), and down-regulation of 17 beta HSD5, and 17 beta HSD2. These studies suggest that reactive prostate stroma and the inflammatory microenvironment may contribute to altered steroid metabolism and increased intratumoral androgens. Published by Elsevier Ltd.
C1 [Piao, Yun-shang; Arnold, Julia T.] NIH, Div Intramural Res, Natl Ctr Complementary & Alternat Med, Bethesda, MD 20892 USA.
[Wiesenfeld, Paddy; Sprando, Robert] US FDA, Div Toxicol, Off Appl Res & Safety Assessment, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA.
RP Arnold, JT (reprint author), NCI, NIH, 9609 Med Ctr Dr,Rm 3W206, Rockville, MD 20850 USA.
EM jarnold@mail.nih.gov
FU National Center for Complementary and Alternative Medicine, National
Institutes of Health, Bethesda, MD [Z01 AT000006-09]
FX The authors thank Dr. Guenter Vollmer (Technical University, Dresden,
Germany) for constructive comments in reviewing this manuscript. This
work was supported by the Intramural Research Program, (Z01 AT000006-09)
National Center for Complementary and Alternative Medicine, National
Institutes of Health, Bethesda, MD.
NR 45
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U1 1
U2 2
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0960-0760
J9 J STEROID BIOCHEM
JI J. Steroid Biochem. Mol. Biol.
PD NOV
PY 2013
VL 138
BP 206
EP 213
DI 10.1016/j.jsbmb.2013.05.016
PG 8
WC Biochemistry & Molecular Biology; Endocrinology & Metabolism
SC Biochemistry & Molecular Biology; Endocrinology & Metabolism
GA 264UK
UT WOS:000327906300022
PM 23770322
ER
PT J
AU Abeliovich, H
Zarei, M
Rigbolt, KTG
Youle, RJ
Dengjel, J
AF Abeliovich, Hagai
Zarei, Mostafa
Rigbolt, Kristoffer T. G.
Youle, Richard J.
Dengjel, Joern
TI Involvement of mitochondrial dynamics in the segregation of
mitochondrial matrix proteins during stationary phase mitophagy
SO NATURE COMMUNICATIONS
LA English
DT Article
ID SACCHAROMYCES-CEREVISIAE; MONITORING AUTOPHAGY; OXIDATIVE STRESS; YEAST;
DEGRADATION; FISSION; GTPASE; FUSION; MUTANTS; COMPLEX
AB Mitophagy, the autophagic degradation of mitochondria, is an important housekeeping function in eukaryotic cells, and defects in mitophagy correlate with ageing phenomena and with several neurodegenerative disorders. A central mechanistic question regarding mitophagy is whether mitochondria are consumed en masse, or whether an active process segregates defective molecules from functional ones within the mitochondrial network, thus allowing a more efficient culling mechanism. Here we combine a proteomic study with a molecular genetics and cell biology approach to determine whether such a segregation process occurs in yeast mitochondria. We find that different mitochondrial matrix proteins undergo mitophagic degradation at distinctly different rates, supporting the active segregation hypothesis. These differential degradation rates depend on mitochondrial dynamics, suggesting a mechanism coupling weak physical segregation with mitochondrial dynamics to achieve a distillation-like effect. In agreement, the rates of mitophagic degradation strongly correlate with the degree of physical segregation of specific matrix proteins.
C1 [Abeliovich, Hagai] Hebrew Univ Jerusalem, Robert H Smith Fac Agr Food & Environm, Inst Biochem Food Sci & Nutr, IL-76100 Rehovot, Israel.
[Abeliovich, Hagai; Youle, Richard J.] Natl Inst Neurol Disorders & Stroke, Surg Neurol Branch, Porter Neurosci Res Ctr, Bethesda, MD 20892 USA.
[Zarei, Mostafa; Rigbolt, Kristoffer T. G.; Dengjel, Joern] Univ Freiburg, Ctr Biol Signaling Studies, FRIAS, D-79104 Freiburg, Germany.
[Zarei, Mostafa; Rigbolt, Kristoffer T. G.; Dengjel, Joern] Univ Freiburg, Ctr Biol Signaling Studies, BIOSS, D-79104 Freiburg, Germany.
[Zarei, Mostafa; Rigbolt, Kristoffer T. G.; Dengjel, Joern] Univ Freiburg, ZBSA Ctr Biol Syst Anal, D-79104 Freiburg, Germany.
[Zarei, Mostafa; Rigbolt, Kristoffer T. G.; Dengjel, Joern] Univ Freiburg, Dept Dermatol, Med Ctr, D-79104 Freiburg, Germany.
RP Abeliovich, H (reprint author), Hebrew Univ Jerusalem, Robert H Smith Fac Agr Food & Environm, Inst Biochem Food Sci & Nutr, POB 12, IL-76100 Rehovot, Israel.
EM hagai.abeliovich@mail.huji.ac.il
FU Israel Science Foundation [1016/07, 422/12]; intramural programme of
NINDS; Excellence Initiative of the German Federal and State Governments
through Freiburg Institute for Advanced Studies (FRIAS); School of Life
Sciences - LifeNet; Center for Biological Signaling Studies; German
Research Foundation, DFG [DE 1757/2-1]; German Ministry for Education
and Research, BMBF [NephAge (031 5896A)]; Danish Natural Sciences
Research Council
FX We thank Orian Shirihai, Leslie Kane, Ian Holt and J.-C. Martinou for
stimulating and fruitful discussions, members of the Youle lab for
support and encouragement, and Dikla Journo-Eckstien for technical
assistance. We also thank J.-C. Martinou and Zvulun Elazar for critical
reading of the manuscript. This work was funded by Israel Science
Foundation grants 1016/07 and 422/12 to H. A., by the intramural
programme of NINDS, and by the Excellence Initiative of the German
Federal and State Governments through Freiburg Institute for Advanced
Studies (FRIAS), School of Life Sciences - LifeNet (JD) and the Center
for Biological Signaling Studies (BIOSS, JD), by grants DE 1757/2-1 from
the German Research Foundation, DFG, and through GerontoSys II - NephAge
(031 5896A) from the German Ministry for Education and Research, BMBF
(JD), and by a grant from the Danish Natural Sciences Research Council
(KTGR).
NR 54
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U1 0
U2 19
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-1723
J9 NAT COMMUN
JI Nat. Commun.
PD NOV
PY 2013
VL 4
AR 2789
DI 10.1038/ncomms3789
PG 11
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 266LJ
UT WOS:000328025000004
PM 24240771
ER
PT J
AU Lencz, T
Guha, S
Liu, CY
Rosenfeld, J
Mukherjee, S
DeRosse, P
John, M
Cheng, LJ
Zhang, CL
Badner, JA
Ikeda, M
Iwata, N
Cichon, S
Rietschel, M
Nothen, MM
Cheng, ATA
Hodgkinson, C
Yuan, QP
Kane, JM
Lee, AT
Pisante, A
Gregersen, PK
Pe'er, I
Malhotra, AK
Goldman, D
Darvasi, A
AF Lencz, Todd
Guha, Saurav
Liu, Chunyu
Rosenfeld, Jeffrey
Mukherjee, Semanti
DeRosse, Pamela
John, Majnu
Cheng, Lijun
Zhang, Chunling
Badner, Judith A.
Ikeda, Masashi
Iwata, Nakao
Cichon, Sven
Rietschel, Marcella
Noethen, Markus M.
Cheng, A. T. A.
Hodgkinson, Colin
Yuan, Qiaoping
Kane, John M.
Lee, Annette T.
Pisante, Anne
Gregersen, Peter K.
Pe'er, Itsik
Malhotra, Anil K.
Goldman, David
Darvasi, Ariel
TI Genome-wide association study implicates NDST3 in schizophrenia and
bipolar disorder
SO NATURE COMMUNICATIONS
LA English
DT Article
ID TRADITIONAL DIAGNOSTIC BOUNDARIES; ASHKENAZI JEWISH POPULATION;
HEPARAN-SULFATE; LINKAGE DISEQUILIBRIUM; COMMON VARIANTS; GENE;
SUSCEPTIBILITY; RISK; EXPRESSION; DISEASE
AB Schizophrenia and bipolar disorder are major psychiatric disorders with high heritability and overlapping genetic variance. Here we perform a genome-wide association study in an ethnically homogeneous cohort of 904 schizophrenia cases and 1,640 controls drawn from the Ashkenazi Jewish population. We identify a novel genome-wide significant risk locus at chromosome 4q26, demonstrating the potential advantages of this founder population for gene discovery. The top single-nucleotide polymorphism (SNP; rs11098403) demonstrates consistent effects across 11 replication and extension cohorts, totalling 23, 191 samples across multiple ethnicities, regardless of diagnosis (schizophrenia or bipolar disorder), resulting in P-meta = 9.49 x 10(-12) (odds ratio (OR) = 1.13, 95% confidence interval (CI): 1.08-1.17) across both disorders and P-meta = 2.67 x 10(-8) (OR = 1.15, 95% CI: 1.08-1.21) for schizophrenia alone. In addition, this intergenic SNP significantly predicts postmortem cerebellar gene expression of NDST3, which encodes an enzyme critical to heparan sulphate metabolism. Heparan sulphate binding is critical to neurite outgrowth, axon formation and synaptic processes thought to be aberrant in these disorders.
C1 [Lencz, Todd; Guha, Saurav; Rosenfeld, Jeffrey; Mukherjee, Semanti; DeRosse, Pamela; John, Majnu; Kane, John M.; Malhotra, Anil K.] North Shore Long Isl Jewish Hlth Syst, Zucker Hillside Hosp Div, Dept Psychiat, Div Res, Glen Oaks, NY 11004 USA.
[Lencz, Todd; Kane, John M.; Malhotra, Anil K.] Feinstein Inst Med Res, Ctr Psychiat Neurosci, Manhasset, NY 11030 USA.
[Lencz, Todd; Kane, John M.; Malhotra, Anil K.] Yeshiva Univ Albert Einstein Coll Med, Dept Psychiat & Behav Sci, Bronx, NY 10461 USA.
[Lencz, Todd; Kane, John M.; Malhotra, Anil K.] Hofstra Univ, Sch Med, Dept Psychiat, Hempstead, NY 11550 USA.
[Lencz, Todd; Kane, John M.; Malhotra, Anil K.] Hofstra Univ, Sch Med, Dept Mol Med, Hempstead, NY 11550 USA.
[Liu, Chunyu] Univ Illinois, Dept Psychiat, Chicago, IL 60612 USA.
[Cheng, Lijun; Zhang, Chunling; Badner, Judith A.] Univ Chicago, Dept Psychiat & Behav Neurosci, Chicago, IL 60637 USA.
[Ikeda, Masashi; Iwata, Nakao] Fujita Hlth Univ, Sch Med, Dept Psychiat, Toyoake, Aichi 4701192, Japan.
[Cichon, Sven; Noethen, Markus M.] Univ Bonn, Inst Human Genet, D-53127 Bonn, Germany.
[Rietschel, Marcella] Univ Mannheim, Cent Inst Mental Hlth, Dept Genet Epidemiol Psychiat, D-68159 Mannheim, Germany.
[Cheng, A. T. A.] Acad Sinica, Inst Biomed Sci, Taipei 115, Taiwan.
[Hodgkinson, Colin; Yuan, Qiaoping; Goldman, David] NIAAA, Neurogenet Lab, Rockville, MD 20852 USA.
[Lee, Annette T.; Gregersen, Peter K.] Feinstein Inst Med Res, Robert S Boas Ctr Human Genet & Genom, Manhasset, NY 11030 USA.
[Pisante, Anne; Darvasi, Ariel] Hebrew Univ Jerusalem, Inst Life Sci, Dept Genet, IL-91904 Jerusalem, Israel.
[Gregersen, Peter K.] Hofstra Univ, Dept Med, Sch Med, Hempstead, NY 11550 USA.
[Pe'er, Itsik] Columbia Univ, Dept Comp Sci, New York, NY 10027 USA.
RP Lencz, T (reprint author), North Shore Long Isl Jewish Hlth Syst, Zucker Hillside Hosp Div, Dept Psychiat, Div Res, Glen Oaks, NY 11004 USA.
EM lencz@lij.edu; ariel@hebrew.edu
RI Cichon, Sven/H-8803-2013; Cichon, Sven/B-9618-2014; Goldman,
David/F-9772-2010; Lencz, Todd/J-3418-2014;
OI Cichon, Sven/0000-0002-9475-086X; Cichon, Sven/0000-0002-9475-086X;
Goldman, David/0000-0002-1724-5405; Lencz, Todd/0000-0001-8586-338X;
Guha, Saurav/0000-0002-0620-5408; Nothen, Markus/0000-0002-8770-2464
FU North Shore-LIJ Health System Foundation; National Institutes of Health
[RC2 MH089964, R01 MH095458, R01 MH084098, P50 MH080173, P30 MH090590,
R01 MH080425]
FX We thank Michael Ryan of the Feinstein Institute Biorepository for
assistance with sample handling and preparation. This work was supported
by the North Shore-LIJ Health System Foundation and the National
Institutes of Health (RC2 MH089964, R01 MH095458 and R01 MH084098 to T.
L.; P50 MH080173 to A. K. M.; P30 MH090590 to J.M.K.; and R01 MH080425
to C. L.). We thank David B. Goldstein for providing summary data from
the Aberdeen and Munich cohorts. We are extremely grateful to
investigators, including Pablo Gejman, John Kelsoe and Nick Craddock,
who have made their genotype data publicly available through dbGAP and
the Wellcome Trust Case-Control Consortium (WTCCC). A full list of the
investigators who contributed to the generation of these data sets is
available from www.wtccc.org.uk as well as the following studies within
dbGAP (http://www.ncbi.nlm.nih.gov/projects/gap):;
/cgi-bin/study.cgi?study_id = phs000167.v1.p1;;
/cgi-bin/study.cgi?study_id = phs000021.v2.p1;;
/cgi-bin/study.cgi?study_id = phs000017.v3.p1.
NR 48
TC 30
Z9 30
U1 3
U2 13
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-1723
J9 NAT COMMUN
JI Nat. Commun.
PD NOV
PY 2013
VL 4
AR 2739
DI 10.1038/ncomms3739
PG 10
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 266KQ
UT WOS:000328023000010
PM 24253340
ER
PT J
AU Singh, N
Ma, B
Leonardo, CC
Ahmad, AS
Narumiya, S
Dore, S
AF Singh, Nilendra
Ma, Bo
Leonardo, Christopher Charles
Ahmad, Abdullah Shafique
Narumiya, Shuh
Dore, Sylvain
TI Role of PGE(2) EP1 Receptor in Intracerebral Hemorrhage-Induced Brain
Injury
SO NEUROTOXICITY RESEARCH
LA English
DT Article
DE Collagenase; Hematoma; Microglia; Neurodegeneration; Prostaglandin
ID AMERICAN-HEART-ASSOCIATION; WIDE THERAPEUTIC WINDOW; FOCAL
CEREBRAL-ISCHEMIA; FUNCTIONAL RECOVERY; CELL-DEATH; MICE; INFLAMMATION;
RAT; EXPRESSION; STROKE
AB Prostaglandin E-2 (PGE(2)) has been described to exert beneficial and detrimental effects in various neurologic disorders. These conflicting roles of PGE(2) could be attributed to its diverse receptor subtypes, EP1-EP4. At present, the precise role of EP1 in intracerebral hemorrhage (ICH) is unknown. Therefore, to elucidate its possible role in ICH, intrastriatal injection of collagenase was given in randomized groups of adult male wildtype (WT) and EP1 receptor knockout (EP1(-/-)) C57BL/6 mice. Functional outcomes including neurologic deficits, rotarod performance, open field activity, and adhesive removal performance were evaluated at 24, 48, and 72 h post-ICH. Lesion volume, cell survival and death, were assessed using Cresyl Violet, and Fluoro-Jade staining, respectively. Microglial activation and phagocytosis were estimated using Iba1 immunoreactivity and fluorescently-labeled microspheres. Following 72 h post-ICH, EP1(-/-) mice showed deteriorated outcomes compared to the WT control mice. These outcomes were demonstrated by elevated neurological deficits, exacerbated lesion volume, and significantly worsened sensorimotor functions. Fluoro-Jade staining showed significantly increased numbers of degenerating neurons and reduced neuronal survival in EP1(-/-) compared to WT mice. To assess in vivo phagocytosis, the number of microspheres phagocytosed by Iba1-positive cells was 145.4 +/- 15.4 % greater in WT compared to EP1(-/-) mice. These data demonstrate that EP1 deletion exacerbates neuro-behavioral impairments following ICH, potentially by slowing down/impairing microglial phagocytosis. A better understanding of this EP1 mechanism could lead to improved intervention strategies for hemorrhagic stroke.
C1 [Singh, Nilendra; Leonardo, Christopher Charles; Ahmad, Abdullah Shafique; Dore, Sylvain] Univ Florida, Dept Anesthesiol, Ctr Translat Res Neurodegenerat Dis, Gainesville, FL 32610 USA.
[Ma, Bo] NIA, Div Neurogenet, Bethesda, MD 21225 USA.
[Narumiya, Shuh] Kyoto Univ, Dept Pharmacol, Kyoto 6068315, Japan.
[Dore, Sylvain] Univ Florida, Dept Neurosci, Gainesville, FL 32610 USA.
[Dore, Sylvain] Univ Florida, Dept Neurol, Gainesville, FL 32610 USA.
[Dore, Sylvain] Univ Florida, Dept Psychiat, Gainesville, FL 32610 USA.
RP Dore, S (reprint author), Univ Florida, Dept Neurosci, Gainesville, FL 32610 USA.
EM sdore@ufl.edu
RI MA, BO/L-6502-2015
OI MA, BO/0000-0001-5922-666X
FU National Institutes of Health [NS046400, AG022971]; American Heart
Association [09POST2080364]
FX We thank all Dore lab team members for their active participation.
National Institutes of Health (NS046400, AG022971) to SD, and the
American Heart Association (09POST2080364) to BM.
NR 62
TC 10
Z9 10
U1 0
U2 2
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1029-8428
EI 1476-3524
J9 NEUROTOX RES
JI Neurotox. Res.
PD NOV
PY 2013
VL 24
IS 4
BP 549
EP 559
DI 10.1007/s12640-013-9410-7
PG 11
WC Neurosciences
SC Neurosciences & Neurology
GA 268CJ
UT WOS:000328145300009
PM 23824501
ER
PT J
AU Apkarian, AV
Neugebauer, V
Koob, G
Edwards, S
Levine, JD
Ferrari, L
Egli, M
Regunathan, S
AF Apkarian, A. Vania
Neugebauer, Volker
Koob, George
Edwards, Scott
Levine, Jon D.
Ferrari, Luiz
Egli, Mark
Regunathan, Soundar
TI Neural mechanisms of pain and alcohol dependence
SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR
LA English
DT Article; Proceedings Paper
CT 42nd Annual Meeting of the Society-for-Neuroscience
CY OCT 13-17, 2012
CL New Orleans, LA
SP Soc Neuroscience
DE Chronic pain; Drug addiction; Alcohol; Reward; Emotion
ID CORTICOTROPIN-RELEASING-FACTOR; MEDIAL PREFRONTAL CORTEX; CHRONIC
BACK-PAIN; PROTEIN-KINASE-C; CENTRAL AMYGDALA NEURONS; SYNAPTIC
PLASTICITY; DECISION-MAKING; CONDITIONED FEAR; CENTRAL NUCLEUS;
ARTHRITIC PAIN
AB An association between chronic pain conditions and alcohol dependence has been revealed in numerous studies with episodes of alcohol abuse antedating chronic pain in some people and alcohol dependence emerging after the onset of chronic pain in others. Alcohol dependence and chronic pain share common neural circuits giving rise to the possibility that chronic pain states could significantly affect alcohol use patterns and that alcohol dependence could influence pain sensitivity. The reward and emotional pathways that regulate drug/alcohol addiction also mediate chronic pain. For example, pain-evoked activation of brain learning and brain reward circuitry may modulate cortical processing of pain and central sensitization mediated by mesocorticolimbic circuitry. Imbalance and reorganization of amygdala-mPFC interactions may not only be important for persistent pain, but also for disorders characterized by the abnormal persistence of emotional-affective states such as drug and alcohol addiction. Further studies are necessary to understand how these neural circuits are regulated in comorbid conditions of alcoholism and chronic pain. In addition, long term alcohol use could induce pain symptoms and may exacerbate chronic pain arising from other sources. While prior studies have established a role of neuroendocrine stress axis mediators in alcohol abuse and neurotoxic effects, these studies have not explored the distinction between the individual impact of alcohol and stress hormones. Future studies should explore the mechanisms mediating the contribution of alcohol and stress axis hormones on pain, an important question in our understanding of the neurobiology of alcohol abuse and chronic pain. Published by Elsevier Inc.
C1 [Apkarian, A. Vania] Northwestern Univ, Sch Med, Dept Neurosci, Chicago, IL USA.
[Neugebauer, Volker] Univ Texas Med Branch, Dept Neurosci & Cell Biol, Galveston, TX 77555 USA.
[Koob, George; Edwards, Scott] Scripps Res Inst, Comm Neurobiol Addict Disorders, La Jolla, CA 92037 USA.
[Levine, Jon D.; Ferrari, Luiz] Univ Calif San Francisco, Div Neurosci NIH Pain Ctr, San Francisco, CA 94143 USA.
[Egli, Mark; Regunathan, Soundar] NIAAA, Div Neurosci & Behav, NIH, Bethesda, MD 20892 USA.
RP Regunathan, S (reprint author), NIAAA, Div Neurosci & Behav, NIH, Bethesda, MD 20892 USA.
EM regunathans@mail.nih.gov
RI koob, george/P-8791-2016;
OI Apkarian, A. Vania/0000-0002-9788-7458
FU NINDS NIH HHS [R01 NS035115, R01 NS038261, R01 NS081121]
NR 120
TC 17
Z9 17
U1 1
U2 12
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0091-3057
J9 PHARMACOL BIOCHEM BE
JI Pharmacol. Biochem. Behav.
PD NOV 1
PY 2013
VL 112
BP 34
EP 41
DI 10.1016/j.pbb.2013.09.008
PG 8
WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy
SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy
GA 265AY
UT WOS:000327923300006
PM 24095683
ER
PT J
AU Mensah, GA
AF Mensah, George A.
TI Introduction: Progress in Cardiovascular Diseases and Diabetes in Africa
SO PROGRESS IN CARDIOVASCULAR DISEASES
LA English
DT Editorial Material
C1 NHLBI, NIH, Bethesda, MD 20892 USA.
RP Mensah, GA (reprint author), NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM george.mensah@nih.gov
NR 6
TC 0
Z9 0
U1 0
U2 3
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0033-0620
EI 1873-1740
J9 PROG CARDIOVASC DIS
JI Prog. Cardiovasc. Dis.
PD NOV-DEC
PY 2013
VL 56
IS 3
BP 232
EP 233
DI 10.1016/j.pcad.2013.10.013
PG 2
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 263TP
UT WOS:000327831200002
PM 24267429
ER
PT J
AU Moran, A
Forouzanfar, M
Sampson, U
Chugh, S
Feigin, V
Mensah, G
AF Moran, Andrew
Forouzanfar, Mohammad
Sampson, Uchechukwu
Chugh, Sumeet
Feigin, Valery
Mensah, George
TI The Epidemiology of Cardiovascular Diseases in Sub-Saharan Africa: The
Global Burden of Diseases, Injuries and Risk Factors 2010 Study
SO PROGRESS IN CARDIOVASCULAR DISEASES
LA English
DT Review
DE Cardiovascular disease; Sub-Saharan Africa; Mortality; Burden of
disease; Global health
ID ISCHEMIC-HEART-DISEASE; SYSTEMATIC ANALYSIS; POPULATION; FAILURE; COMMON
AB The epidemiology of cardiovascular diseases in sub-Saharan Africa is unique among world regions, with about half of cardiovascular diseases (CVDs) due to causes other than atherosclerosis. CVD epidemiology data are sparse and of uneven quality in sub-Saharan Africa. Using the available data, the Global Burden of Diseases, Risk Factors, and Injuries (GBD) 2010 Study estimated CVD mortality and burden of disease in sub-Saharan Africa in 1990 and 2010. The leading CVD cause of death and disability in 2010 in sub-Saharan Africa was stroke; the largest relative increases in CVD burden between 1990 and 2010 were in atrial fibrillation and peripheral arterial disease. CVD deaths constituted only 8.8% of all deaths and 3.5% of all disability-adjusted life years (DALYs) in sub-Sahara Africa, less than a quarter of the proportion of deaths and burden attributed to CVD in high income regions. However, CVD deaths in sub-Saharan Africa occur at younger ages on average than in the rest of the world. It remains uncertain if increased urbanization and life expectancy in some parts of sub-Saharan African nations will transition the region to higher CVD burden in future years. (C) 2013 Elsevier Inc. All rights reserved.
C1 [Moran, Andrew] Columbia Univ, Div Gen Med, Med Ctr, New York, NY 10032 USA.
[Forouzanfar, Mohammad] Univ Washington, Inst Hlth Metr & Evaluat, Seattle, WA 98195 USA.
[Sampson, Uchechukwu] Vanderbilt Univ, Div Cardiovasc Med, Nashville, TN 37235 USA.
[Chugh, Sumeet] Cedars Sinai Med Ctr, Div Cardiol, Los Angeles, CA 90048 USA.
[Feigin, Valery] Auckland Univ Technol, Auckland, New Zealand.
[Mensah, George] NHLBI, NIH, Bethesda, MD 20892 USA.
RP Moran, A (reprint author), Columbia Univ, Div Gen Med, Presbyterian Hosp, 9th Floor East Room 105,622 West 168th St, New York, NY 10032 USA.
EM aem35@columbia.edu
FU NHLBI NIH HHS [K08 HL089675]
NR 25
TC 32
Z9 32
U1 6
U2 16
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0033-0620
EI 1873-1740
J9 PROG CARDIOVASC DIS
JI Prog. Cardiovasc. Dis.
PD NOV-DEC
PY 2013
VL 56
IS 3
BP 234
EP 239
DI 10.1016/j.pcad.2013.09.019
PG 6
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 263TP
UT WOS:000327831200003
PM 24267430
ER
PT J
AU Mensah, GA
AF Mensah, George A.
TI Descriptive Epidemiology of Cardiovascular Risk Factors and Diabetes in
Sub-Saharan Africa
SO PROGRESS IN CARDIOVASCULAR DISEASES
LA English
DT Review
DE Cardiovascular diseases; Sub-Saharan Africa; Cardiovascular risk factors
ID SYSTEMATIC ANALYSIS; GLOBAL BURDEN; HEART-DISEASE;
MYOCARDIAL-INFARCTION; SOUTH-AFRICA; 21 REGIONS; URBANIZATION;
TRANSITION; POPULATION; INTERHEART
AB Reliable data on risk factor levels, exposure history, and population distribution can help inform policies and programs for disease prevention and control. With rare exception however, ideal local data on major risk factors and causes of death and disease burden have been scarce in sub-Saharan Africa (SSA). Basic community surveys in some countries and recent systematic analysis of disease burden attributable to 67 risk factors and risk factor clusters in 21 regions of the world provide an opportunity to examine and relate diabetes and cardiovascular risk factors to mortality and burden in SSA. Rising body mass index, especially in women in Southern Africa; and rising systolic blood pressure in East Africa for both sexes, and in West Africa for women are the major cardiometabolic risk factors. Harmful use of alcohol, especially in Southern SSA, tobacco use, and physical inactivity are also important. Improving vital registration and risk factor surveillance remain major challenges. Published by Elsevier Inc.
C1 [Mensah, George A.] NHLBI, Off Director, NIH, Bethesda, MD 20892 USA.
RP Mensah, GA (reprint author), NHLBI, NIH, IOD, 31 Ctr Dr MSC 2486, Bethesda, MD 20892 USA.
EM george.mensah@nih.gov
NR 45
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Z9 14
U1 3
U2 10
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0033-0620
EI 1873-1740
J9 PROG CARDIOVASC DIS
JI Prog. Cardiovasc. Dis.
PD NOV-DEC
PY 2013
VL 56
IS 3
BP 240
EP 250
DI 10.1016/j.pcad.2013.10.014
PG 11
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 263TP
UT WOS:000327831200004
PM 24267431
ER
PT J
AU Tekola-Ayele, F
Adeyemo, AA
Rotimi, CN
AF Tekola-Ayele, Fasil
Adeyemo, Adebowale A.
Rotimi, Charles N.
TI Genetic Epidemiology of Type 2 Diabetes and Cardiovascular Diseases in
Africa
SO PROGRESS IN CARDIOVASCULAR DISEASES
LA English
DT Review
DE Type 2 diabetes; Cardiovascular diseases; Genetics; Epidemiology; Africa
ID CORONARY-ARTERY-DISEASE; QUANTITATIVE TRAIT LOCI; NITRIC-OXIDE SYNTHASE;
GENOME-WIDE SEARCH; BLOOD-PRESSURE; WEST AFRICANS; SUSCEPTIBILITY GENES;
FAMILY-HISTORY; MELLITUS AADM; HEART-DISEASE
AB The burdens of type 2 diabetes (T2D) and cardiovascular diseases (CVD) are increasing in Africa. T2D and CVD are the result of the complex interaction between inherited characteristics, lifestyle, and environmental factors. The epidemic of obesity is largely behind the exploding global incidence of T2D. However, not all obese individuals develop diabetes and positive family history is a powerful risk factor for diabetes and CVD. Recent implementations of high throughput genotyping and sequencing approaches have advanced our understanding of the genetic basis of diabetes and CVD by identifying several genomic loci that were not previously linked to the pathobiology of these diseases. However, African populations have not been adequately represented in these global genomic efforts. Here, we summarize the state of knowledge of the genetic epidemiology of T2D and CVD in Africa and highlight new genomic initiatives that promise to inform disease etiology, public health and clinical medicine in Africa. Published by Elsevier Inc.
C1 [Tekola-Ayele, Fasil; Adeyemo, Adebowale A.; Rotimi, Charles N.] NHGRI, Ctr Res Genom & Global Hlth, NIH, Bethesda, MD 20892 USA.
RP Rotimi, CN (reprint author), Bldg 12A,Room 4047 12 South Dr,MSC 5635, Bethesda, MD 20892 USA.
EM rotimic@mail.nih.gov
OI Adeyemo, Adebowale/0000-0002-3105-3231; Tekola-Ayele,
Fasil/0000-0003-4194-9370
FU Intramural Research Program of the Center for Research on Genomics and
Global Health; National Human Genome Research Institute; National
Institute of Diabetes and Digestive and Kidney Diseases; Center for
Information Technology; Office of the Director at the National
Institutes of Health [1ZIAHG200362-02]
FX This work was supported by the Intramural Research Program of the Center
for Research on Genomics and Global Health. The Center for Research on
Genomics and Global Health is supported by the National Human Genome
Research Institute, the National Institute of Diabetes and Digestive and
Kidney Diseases, the Center for Information Technology, and the Office
of the Director at the National Institutes of Health (1ZIAHG200362-02).
NR 78
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U1 0
U2 13
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0033-0620
EI 1873-1740
J9 PROG CARDIOVASC DIS
JI Prog. Cardiovasc. Dis.
PD NOV-DEC
PY 2013
VL 56
IS 3
BP 251
EP 260
DI 10.1016/j.pcad.2013.09.013
PG 10
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 263TP
UT WOS:000327831200005
PM 24267432
ER
PT J
AU O'Connor, MY
Thoreson, CK
Ramsey, NLM
Ricks, M
Sumner, AE
AF O'Connor, Michelle Y.
Thoreson, Caroline K.
Ramsey, Natalie L. M.
Ricks, Madia
Sumner, Anne E.
TI The Uncertain Significance of Low Vitamin D Levels in African Descent
Populations: A Review of the Bone and Cardiometabolic Literature
SO PROGRESS IN CARDIOVASCULAR DISEASES
LA English
DT Review
DE Vitamin D; Melanin; Lactose Intolerance; Africans; African Diaspora;
African-Americans
ID SERUM 25-HYDROXYVITAMIN D; NUTRITION EXAMINATION SURVEY; RURAL GAMBIAN
WOMEN; 3RD NATIONAL-HEALTH; D SUPPLEMENTATION; BLOOD-PRESSURE;
LACTOSE-INTOLERANCE; MINERAL DENSITY; PARATHYROID-HORMONE;
RACIAL-DIFFERENCES
AB Vitamin D levels in people of African descent are often described as inadequate or deficient. Whether low vitamin D levels in people of African descent lead to compromised bone or cardiometabolic health is unknown. Clarity on this issue is essential because if clinically significant vitamin D deficiency is present, vitamin D supplementation is necessary. However, if vitamin D is metabolically sufficient, vitamin D supplementation could be wasteful of scarce resources and even harmful. In this review vitamin D physiology is described with a focus on issues specific to populations of African descent such as the influence of melanin on endogenous vitamin D production and lactose intolerance on the willingness of people to ingest vitamin D fortified foods. Then data on the relationship of vitamin D to bone and cardiometabolic health in people of African descent are evaluated. Published by Elsevier Inc.
C1 [O'Connor, Michelle Y.; Thoreson, Caroline K.; Ramsey, Natalie L. M.; Ricks, Madia; Sumner, Anne E.] NIDDK, Diabet Endocrinol & Obes Branch, NIH, Bethesda, MD 20892 USA.
RP Sumner, AE (reprint author), Bld 10-CRC,Rm 6-5940,MSC 1612,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM AnneS@intra.niddk.nih.gov
FU Intramural Research Program of NIDDK
FX All the authors were supported by the Intramural Research Program of
NIDDK.
NR 78
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U1 1
U2 6
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0033-0620
EI 1873-1740
J9 PROG CARDIOVASC DIS
JI Prog. Cardiovasc. Dis.
PD NOV-DEC
PY 2013
VL 56
IS 3
BP 261
EP 269
DI 10.1016/j.pcad.2013.10.015
PG 9
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 263TP
UT WOS:000327831200006
PM 24267433
ER
PT J
AU Sampson, UKA
Amuyunzu-Nyamongo, M
Mensah, GA
AF Sampson, Uchechukwu K. A.
Amuyunzu-Nyamongo, Mary
Mensah, George A.
TI Health Promotion and Cardiovascular Disease Prevention in Sub-Saharan
Africa
SO PROGRESS IN CARDIOVASCULAR DISEASES
LA English
DT Review
DE Cardiovascular disease; Sub-Saharan Africa; Non-communicable diseases;
Health promotion; Prevention
ID CORONARY RISK-FACTOR; SYSTEMATIC ANALYSIS; BLOOD-PRESSURE;
HEART-DISEASE; GLOBAL BURDEN; 21 REGIONS; LITERACY; MORTALITY;
COMMUNITY; OUTCOMES
AB Recent population studies demonstrate an increasing burden of cardiovascular disease (CVD) and related risk factors in sub-Saharan Africa (SSA). The mitigation or reversal of this trend calls for effective health promotion and preventive interventions. In this article, we review the core principles, challenges, and progress in promoting cardiovascular health with special emphasis on interventions to address physical inactivity, poor diet, tobacco use, and adverse cardiometabolic risk factor trends in SSA. We focus on the five essential strategies of the Ottawa Charter for Health Promotion. Successes highlighted include community-based interventions in Ghana, Nigeria, South Africa, and Mauritius and school-based programs in Kenya, Namibia, and Swaziland. We address the major challenge of developing integrated interventions, and showcase partnerships opportunities. We conclude by calling for intersectoral partnerships for effective and sustainable intervention strategies to advance cardiovascular health promotion and close the implementation gap in accordance with the 2009 Nairobi Call to Action on Health Promotion. Published by Elsevier Inc.
C1 [Sampson, Uchechukwu K. A.] Vanderbilt Univ, Med Ctr, Dept Med, Nashville, TN 37232 USA.
[Sampson, Uchechukwu K. A.] VUMC, Dept Pathol Microbiol & Immunol, Nashville, TN USA.
[Sampson, Uchechukwu K. A.] VUMC, Dept Radiol & Radiol Sci, Nashville, TN USA.
[Amuyunzu-Nyamongo, Mary] African Inst Hlth & Dev, Nairobi, Kenya.
[Amuyunzu-Nyamongo, Mary] Consortium NCD Prevent & Control Sub Saharan Afri, Nairobi, Kenya.
[Mensah, George A.] NHLBI, Off Director, NIH, Bethesda, MD 20892 USA.
RP Sampson, UKA (reprint author), Vanderbilt Univ, Med Ctr, Sect Cardiovasc Dis Prevent, 315 Preston Res Bldg,2220 Pierce Ave, Nashville, TN 37232 USA.
EM u.sampson@vanderbilt.edu
FU Robert Wood Johnson Foundation
FX The authors do not have any conflicts of interest to disclose. Dr.
Sampson's effort was supported in part by Harold Amos Medical Faculty
Award of the Robert Wood Johnson Foundation.
NR 58
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U1 4
U2 22
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0033-0620
EI 1873-1740
J9 PROG CARDIOVASC DIS
JI Prog. Cardiovasc. Dis.
PD NOV-DEC
PY 2013
VL 56
IS 3
BP 344
EP 355
DI 10.1016/j.pcad.2013.10.007
PG 12
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 263TP
UT WOS:000327831200015
PM 24267442
ER
PT J
AU Stover, AM
Reeve, BB
Piper, BF
Alfano, CM
Smith, AW
Mitchell, SA
Bernstein, L
Baumgartner, KB
McTiernan, A
Ballard-Barbash, R
AF Stover, Angela M.
Reeve, Bryce B.
Piper, Barbara F.
Alfano, Catherine M.
Smith, Ashley Wilder
Mitchell, Sandra A.
Bernstein, Leslie
Baumgartner, Kathy B.
McTiernan, Anne
Ballard-Barbash, Rachel
TI Deriving clinically meaningful cut-scores for fatigue in a cohort of
breast cancer survivors: a Health, Eating, Activity, and Lifestyle
(HEAL) Study
SO QUALITY OF LIFE RESEARCH
LA English
DT Article
DE Cancer-related fatigue; Breast cancer survivors; Measurement; Piper
Fatigue Scale; Health-related quality of life
ID QUALITY-OF-LIFE; PATIENT-REPORTED OUTCOMES; UNITED-STATES; WOMEN;
DIAGNOSIS; CHEMOTHERAPY; EXPLORATION; PREVALENCE; RECURRENCE; DEPRESSION
AB To empirically determine clinically meaningful cut-scores on the 0-10 response scale of the revised Piper Fatigue Scale (PFS-R) and its shorter version (PFS-12). Breast cancer survivors were classified (i.e., none, mild, moderate, or severe fatigue) based on the cut-scores, and relationships between these cut-scores and decrements in health-related quality of life (HRQOL) were examined.
A total of 857 breast cancer survivors, stages in situ-IIIa, from the Health, Eating, Activity, and Lifestyle (HEAL) Study were eligible. Survivors completed the PFS-R, SF-36, and a sexual health scale approximately 3 years after diagnosis. Multivariate analysis of covariance was used to examine five fatigue severity cut-score models, controlling for demographics, clinical characteristics, comorbidity, and antidepressant use. Multivariate regression was used to examine HRQOL decrements by cut-score category.
Analyses supported two similar fatigue severity cut-score models for the PFS-R and PFS-12: Model A.) none (0), mild (1-3), moderate (4-6), and severe (7-10); and Model D.) none (0), mild (1-2), moderate (3-5), and severe (6-10). For every threshold increase in fatigue severity, clinically meaningful decrements in physical, mental, and sexual health scores were observed, supporting construct validity of the fatigue cut-scores.
Standardized fatigue cut-scores may enhance interpretability and comparability across studies and populations and guide treating planning.
C1 [Stover, Angela M.] Univ N Carolina, Dept Hlth Behav, Chapel Hill, NC 27599 USA.
[Reeve, Bryce B.] Univ N Carolina, Chapel Hill, NC 27599 USA.
[Piper, Barbara F.] Natl Univ, San Diego, CA USA.
[Alfano, Catherine M.; Smith, Ashley Wilder; Mitchell, Sandra A.; Ballard-Barbash, Rachel] NCI, Frederick, MD 21701 USA.
[Bernstein, Leslie] City Hope Natl Med Ctr, Duarte, CA 91010 USA.
[Baumgartner, Kathy B.] Univ Louisville, Louisville, KY 40292 USA.
[McTiernan, Anne] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
RP Reeve, BB (reprint author), Univ N Carolina, 1101-D McGavran Greenberg Hall,Campus Box 7411, Chapel Hill, NC 27599 USA.
EM bbreeve@email.unc.edu
FU NCI [N01-CN-75036-20, N01-CN-05228, N01-PC-67010]; UNC Lineberger
Comprehensive Cancer Center Cancer Control and Education (CCEP)
Predoctoral Fellowship [5R25-CA057726]
FX The parent HEAL Study was supported by NCI contracts N01-CN-75036-20,
N01-CN-05228, and N01-PC-67010. The first author is supported by a UNC
Lineberger Comprehensive Cancer Center Cancer Control and Education
(CCEP) Predoctoral Fellowship (5R25-CA057726).
NR 60
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PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0962-9343
EI 1573-2649
J9 QUAL LIFE RES
JI Qual. Life Res.
PD NOV
PY 2013
VL 22
IS 9
BP 2279
EP 2292
DI 10.1007/s11136-013-0360-6
PG 14
WC Health Care Sciences & Services; Health Policy & Services; Public,
Environmental & Occupational Health
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health
GA 268ZB
UT WOS:000328208300003
PM 23420495
ER
PT J
AU Paz, SH
Slotkin, J
McKean-Cowdin, R
Lee, P
Owsley, C
Vitale, S
Varma, R
Gershon, R
Hays, RD
AF Paz, Sylvia H.
Slotkin, Jerry
McKean-Cowdin, Roberta
Lee, Paul
Owsley, Cynthia
Vitale, Susan
Varma, Rohit
Gershon, Richard
Hays, Ron D.
TI Development of a vision-targeted health-related quality of life item
measure
SO QUALITY OF LIFE RESEARCH
LA English
DT Article
DE Vision-related quality of life; NIH Toolbox; Instrument development;
Instrument psychometric evaluation and calibration
ID VISUAL FUNCTION QUESTIONNAIRE; GRAVES OPHTHALMOPATHY; GO-QOL;
PSYCHOMETRIC PROPERTIES; OUTCOMES MEASUREMENT; REFRACTIVE STATUS; RASCH
ANALYSIS; DRY EYE; VALIDITY; DISEASE
AB To develop a vision-targeted health-related quality of life (HRQOL) measure for the NIH Toolbox for the Assessment of Neurological and Behavioral Function.
We conducted a review of existing vision-targeted HRQOL surveys and identified color vision, low luminance vision, distance vision, general vision, near vision, ocular symptoms, psychosocial well-being, and role performance domains. Items in existing survey instruments were sorted into these domains. We selected non-redundant items and revised them to improve clarity and to limit the number of different response options. We conducted 10 cognitive interviews to evaluate the items. Finally, we revised the items and administered them to 819 individuals to calibrate the items and estimate the measure's reliability and validity.
The field test provided support for the 53-item vision-targeted HRQOL measure encompassing 6 domains: color vision, distance vision, near vision, ocular symptoms, psychosocial well-being, and role performance. The domain scores had high levels of reliability (coefficient alphas ranged from 0.848 to 0.940). Validity was supported by high correlations between National Eye Institute Visual Function Questionnaire scales and the new-vision-targeted scales (highest values were 0.771 between psychosocial well-being and mental health, and 0.729 between role performance and role difficulties), and by lower mean scores in those groups self-reporting eye disease (F statistic with p < 0.01 for all comparisons except cataract with ocular symptoms, psychosocial well-being, and role performance scales).
This vision-targeted HRQOL measure provides a basis for comprehensive assessment of the impact of eye diseases and treatments on daily functioning and well-being in adults.
C1 [Paz, Sylvia H.; Hays, Ron D.] Univ Calif Los Angeles, Sch Med, Dept Med, Div Gen Internal Med & Hlth Serv Res, Los Angeles, CA 90095 USA.
[Slotkin, Jerry; Gershon, Richard] Northwestern Univ Feinberg, Sch Med, Dept Med Social Sci, Chicago, IL 60611 USA.
[McKean-Cowdin, Roberta; Varma, Rohit] Univ So Calif, Keck Sch Med, Dept Ophthalmol, Doheny Eye Inst, Los Angeles, CA 90033 USA.
[Lee, Paul] Duke Univ, Dept Ophthalmol, Durham, NC 27710 USA.
[Owsley, Cynthia] Univ Alabama Birmingham, Dept Ophthalmol, Sch Med, Birmingham, AL 35294 USA.
[Vitale, Susan] NEI, Div Epidemiol & Clin Applicat, NIH, Bethesda, MD 20892 USA.
RP Paz, SH (reprint author), Univ Calif Los Angeles, Sch Med, Dept Med, Div Gen Internal Med & Hlth Serv Res, 911 Broxton Ave, Los Angeles, CA 90095 USA.
EM shpaz@ucla.edu
OI Lee, Paul/0000-0002-3338-136X
FU Blueprint for Neuroscience Research, National Institutes of Health
[HHS-N-260-2006-00007-C]; NIA [P30AG021684, P30-AG028748]; NCMHD
[P20MD000182]
FX This study was supported by the Blueprint for Neuroscience Research,
National Institutes of Health under Contract No. HHS-N-260-2006-00007-C.
Drs. Hays and Paz were also supported in part by NIA grant P30AG021684.
Dr. Hays was additionally supported in part by NIA grant P30-AG028748
and the NCMHD P20MD000182.
NR 36
TC 5
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U1 1
U2 8
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0962-9343
EI 1573-2649
J9 QUAL LIFE RES
JI Qual. Life Res.
PD NOV
PY 2013
VL 22
IS 9
BP 2477
EP 2487
DI 10.1007/s11136-013-0365-1
PG 11
WC Health Care Sciences & Services; Health Policy & Services; Public,
Environmental & Occupational Health
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health
GA 268ZB
UT WOS:000328208300022
PM 23475688
ER
PT J
AU Ren, JQ
Stroncek, DF
Zhao, YD
Jin, P
Castiello, L
Civini, S
Wang, H
Feng, J
Tran, K
Kuznetsov, SA
Robey, PG
Sabatino, M
AF Ren, Jiaqiang
Stroncek, David F.
Zhao, Yingdong
Jin, Ping
Castiello, Luciano
Civini, Sara
Wang, Huan
Feng, Ji
Tran, Katherine
Kuznetsov, Sergei A.
Robey, Pamela G.
Sabatino, Marianna
TI Intra-subject variability in human bone marrow stromal cell (BMSC)
replicative senescence: Molecular changes associated with BMSC
senescence
SO STEM CELL RESEARCH
LA English
DT Article
ID MESENCHYMAL STEM-CELLS; AMYOTROPHIC-LATERAL-SCLEROSIS; GENE; CULTURE;
DIFFERENTIATION; OSTEOGENESIS; TRANSPLANTATION; IDENTIFICATION;
PROLIFERATION; THERAPY
AB The outcomes of clinical trials using bone marrow stromal cell (BMSC) are variable; the degree of the expansion of BMSCs during clinical manufacturing may contribute to this variability since cell expansion is limited by senescence. Human BMSCs from aspirates of healthy subjects were subcultured serially until cell growth stopped. Phenotype and functional measurements of BMSCs from two subjects including senescence-associated beta-galactosidase staining and colony formation efficiency changed from an early to a senescence pattern at passage 6 or 7. Transcriptome analysis of 10 early and 15 late passage BMSC samples from 5 subjects revealed 2122 differentially expressed genes, which were associated with immune response, development, and cell proliferation pathways. Analysis of 57 serial BMSC samples from 7 donors revealed that the change from an early to senescent profile was variable among subjects and occurred prior to changes in phenotypes. BMSC age expressed as a percentage of maximum population doublings (PDs) was a good indicator for an early or senescence transcription signature but this measure of BMSC life span can only be calculated after expanding BMSCs to senescence. In order to find a more useful surrogate measure of BMSC age, we used a computational biology approach to identify a set of genes whose expression at each passage would predict elapsed age of BMSCs. A total of 155 genes were highly correlated with BMSC age. A least angle regression algorithm identified a set of 24 BMSC age-predictive genes. In conclusion, the onset of senescence-associated molecular changes was variable and preceded changes in other indicators of BMSC quality and senescence. The 24 BMSC age predictive genes will be useful in assessing the quality of clinical BMSC products. Published by Elsevier B.V.
C1 [Ren, Jiaqiang; Stroncek, David F.; Jin, Ping; Castiello, Luciano; Civini, Sara; Wang, Huan; Feng, Ji; Tran, Katherine; Sabatino, Marianna] NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA.
[Zhao, Yingdong] NCI, Biometr Res Branch, Div Canc Treatment & Diag, Rockville, MD 20852 USA.
[Kuznetsov, Sergei A.; Robey, Pamela G.] Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD 20892 USA.
RP Stroncek, DF (reprint author), NIH, Dept Transfus Med, Ctr Clin, Bldg 10,Room 1C711, Bethesda, MD 20892 USA.
EM renj@mail.nih.gov; DStroncek@cc.nih.gov; zhaoy@ctep.nci.nih.gov;
Pjin@cc.nih.gov; castiellol@cc.nih.gov; civinis@cc.nih.gov;
Heidi.wang@nih.gov; fenj2@cc.nih.gov; katherine.tran@nih.gov;
skuznetsov@dir.nidcr.nih.gov; probey@dir.nidcr.nih.gov;
sabatinom@cc.nih.gov
RI Robey, Pamela/H-1429-2011; Castiello, Luciano/K-8616-2016
OI Robey, Pamela/0000-0002-5316-5576; Castiello,
Luciano/0000-0001-7146-3158
FU NIH Bone Marrow Stromal Cell Transplantation Center (BMSCTC); Department
of Transfusion Medicine, Clinical Center NIH
FX The authors thank the staff of the Cell Processing Laboratory,
Department of Transfusion Medicine, Clinical Center, NIH for their
support of these studies. We also thank Dr. Francesco Marincola and Dr.
Ena Wang (Department of Transfusion Medicine, Clinical. Center; NIH) for
useful discussions and comments on the manuscript. This work was funded
by NIH Bone Marrow Stromal Cell Transplantation Center (BMSCTC) and the
Department of Transfusion Medicine, Clinical Center NIH. The authors
declared no conflict of interest.
NR 51
TC 19
Z9 20
U1 0
U2 4
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1873-5061
EI 1876-7753
J9 STEM CELL RES
JI Stem Cell Res.
PD NOV
PY 2013
VL 11
IS 3
BP 1060
EP 1073
DI 10.1016/j.scr.2013.07.005
PG 14
WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell
Biology
SC Cell Biology; Biotechnology & Applied Microbiology
GA 264UA
UT WOS:000327905300009
PM 23959330
ER
PT J
AU Tsang, WH
Wang, B
Wong, WK
Shi, S
Chen, X
He, XJ
Gu, S
Hu, JB
Wang, CD
Liu, PC
Lu, G
Chen, XF
Zhao, H
Poon, WS
Chan, WY
Feng, B
AF Tsang, Wan-Hong
Wang, Bin
Wong, Wing Ki
Shi, Shuo
Chen, Xiao
He, Xiangjun
Gu, Shen
Hu, Jiabiao
Wang, Chengdong
Liu, Pi-Chu
Lu, Gang
Chen, Xiongfong
Zhao, Hui
Poon, Wai-Sang
Chan, Wai-Yee
Feng, Bo
TI LIF-dependent primitive neural stem cells derived from mouse ES cells
represent a reversible stage of neural commitment
SO STEM CELL RESEARCH
LA English
DT Article
ID IN-VITRO; DEFAULT MECHANISM; SELF-RENEWAL; DIFFERENTIATION; INDUCTION;
PLURIPOTENCY; PRECURSORS; FATE; FGF; NEUROGENESIS
AB Primitive neural stem cells (NSCs) define an early stage of neural induction, thus provide a model to understand the mechanism that controls initial neural commitment. In this study, we investigated primitive NSCs derived from mouse embryonic stem cells (ESCs). By genome-wide transcriptional profiling, we revealed their unique signature and depicted the molecular changes underlying critical cell fate transitions during early neural induction at a global level. Together with qRT-PCR analysis, our data illustrated that primitive NSCs retained expression of key pluripotency genes Oct4 and Nanog, while exhibiting repression of other pluripotency-related genes Zscan4, Foxp1 and Dusp9 and up-regulation of neural markers Sox1 and Hes1. The early differentiation feature in primitive NSCs was also supported by their intermediate characters on cell cycle profiles. Moreover, re-plating primitive NSCs back to ESC culture condition could reverse them back to ESC stage, as shown by reversible regulation of marker genes, cell cycle profile changes and enhanced embryoid body formation. In addition, our microarray analysis also identified genes differentially expressed in primitive NSCs, and loss-of-function analysis demonstrated that Hes1 and Ccdc141 play important function at this stage, opening up an opportunity to further understand the regulation of early neural commitment. (C) 2013 Elsevier B.V. All rights reserved.
C1 [Tsang, Wan-Hong; Wang, Bin; Wong, Wing Ki; Shi, Shuo; Chen, Xiao; He, Xiangjun; Gu, Shen; Hu, Jiabiao; Wang, Chengdong; Lu, Gang; Zhao, Hui; Chan, Wai-Yee; Feng, Bo] Chinese Univ Hong Kong, Sch Biomed Sci, Fac Med, Key Lab Regenerat Med,Minist Educ, Shatin, Hong Kong, Peoples R China.
[Wang, Bin; Shi, Shuo; Lu, Gang; Zhao, Hui; Poon, Wai-Sang; Chan, Wai-Yee; Feng, Bo] CUHK Shenzhen Res Inst, Shenzhen, Peoples R China.
[Chen, Xiao] Zhejiang Univ, Sch Med, Ctr Stem Cell & Tissue Engn, Hangzhou 310003, Zhejiang, Peoples R China.
[Liu, Pi-Chu; Lu, Gang; Poon, Wai-Sang] Chinese Univ Hong Kong, Dept Surg, Shatin, Hong Kong, Peoples R China.
[Chen, Xiongfong] NCI, Adv Biomed Comp Ctr, NIH, Frederick, MD 21702 USA.
RP Chan, WY (reprint author), Chinese Univ Hong Kong, Sch Biomed Sci, Area 39, Room G03,Lo Kwee Seong Integrated Biomed Sci Bldg, Shatin, Hong Kong, Peoples R China.
EM chanwy@cuhk.edu.hk; fengbo@cuhk.edu.hk
RI Chen, Xiao/A-4384-2009; Poon, Wai Sang/F-1558-2011; Zhao,
Hui/B-8429-2016; Feng, Bo/D-7831-2014
OI Chen, Xiao/0000-0002-4438-5286;
FU Research Grants Council of Hong Kong [CUHK 464411, HKUST T13-607/12R];
National Natural Science Foundation of China [A.03.12.00601]
FX This work was supported by grants from the Research Grants Council of
Hong Kong (CUHK 464411 to B.F.) (HKUST T13-607/12R to Y.I. et al.); and
in part by funds from the National Natural Science Foundation of China
(A.03.12.00601 to B.F.). We are grateful to Huck-Hui Ng for ESC and
EpiSC lines. We thank Jianwei Ren and William K. F. Tse for their
critical comments on the manuscript.
NR 52
TC 3
Z9 3
U1 0
U2 7
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1873-5061
EI 1876-7753
J9 STEM CELL RES
JI Stem Cell Res.
PD NOV
PY 2013
VL 11
IS 3
BP 1091
EP 1102
DI 10.1016/j.scr.2013.07.007
PG 12
WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell
Biology
SC Cell Biology; Biotechnology & Applied Microbiology
GA 264UA
UT WOS:000327905300011
PM 23973799
ER
PT J
AU Abe, Y
Sakairi, T
Beeson, C
Kopp, JB
AF Abe, Yoshifusa
Sakairi, Toru
Beeson, Craig
Kopp, Jeffrey B.
TI TGF-beta 1 stimulates mitochondrial oxidative phosphorylation and
generation of reactive oxygen species in cultured mouse podocytes,
mediated in part by the mTOR pathway
SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
LA English
DT Article
DE podocyte; mitochondria; bioenergetics; TGF-beta 1; oxygen consumption
rate; extracellular acidification rate
ID GROWTH-FACTOR-BETA; MAMMALIAN TARGET; TGF-BETA; NAD(P)H OXIDASE;
GENE-EXPRESSION; TRANSGENIC MICE; RENAL-DISEASE; RAPAMYCIN; APOPTOSIS;
KIDNEY
AB TGF-beta 1 stimulates mitochondrial oxidative phosphorylation and generation of reactive oxygen species in cultured mouse podocytes, mediated in part by the mTOR pathway. Am J Physiol Renal Physiol 305: F1477-F1490, 2013. First published September 18, 2013; doi:10.1152/ajprenal.00182.2013.-Transforming growth factor (TGF)-beta has been associated with podocyte injury; we have examined its effect on podocyte bioenergetics. We studied transformed mouse podocytes, exposed to TGF-beta 1, using a label-free assay system, Seahorse XF24, which measures oxygen consumption rates (OCR) and extracellular acidification rates (ECAR). Both basal OCR and ATP generation-coupled OCR were significantly higher in podocytes exposed to 0.3-10 ng/ml of TGF-beta 1 for 24, 48, and 72 h. TGF-beta 1 (3 ng/ml) increased oxidative capacity 75%, and 96% relative to control after 48 and 72 h, respectively. ATP content was increased 19% and 30% relative to control after a 48- and 72-h exposure, respectively. Under conditions of maximal mitochondrial function, TGF-beta 1 increased palmitate-driven OCR by 49%. Thus, TGF-beta 1 increases mitochondrial oxygen consumption and ATP generation in the presence of diverse energy substrates. TGF-beta 1 did not increase cell number or mitochondrial DNA copy number but did increase mitochondrial membrane potential (MMP), which could explain the OCR increase. Reactive oxygen species (ROS) increased by 32% after TGF-beta 1 exposure for 48 h. TGF-beta activated the mammalian target of rapamycin (mTOR) pathway, and rapamycin reduced the TGF-beta 1-stimulated increases in OCR, ECAR, ATP generation, cellular metabolic activity, and protein generation. Our data suggest that TGF-beta 1, acting, in part, via mTOR, increases mitochondrial MMP and OCR, resulting in increased ROS generation and that this may contribute to podocyte injury.
C1 [Abe, Yoshifusa] Showa Univ Sch Med, Dept Pediat, Tokyo, Japan.
[Abe, Yoshifusa; Kopp, Jeffrey B.] Natl Inst Diabet & Digest & Kidney Dis, Kidney Dis Sect, NIH, Bethesda, MD USA.
[Sakairi, Toru] Gunma Univ Grad Sch Med, Dept Med & Clin Sci, Maebashi, Gumma, Japan.
[Beeson, Craig] Med Univ S Carolina, Dept Pharmaceut & Biomed Sci, Charleston, SC 29425 USA.
RP Kopp, JB (reprint author), NIH, 10 Ctr Dr, Bethesda, MD 20892 USA.
EM jbkopp@nih.gov
FU National Institute of Diabetes and Digestive and Kidney Diseases
Intramural Research Program [ZO1-DK043308]
FX This study was supported by the National Institute of Diabetes and
Digestive and Kidney Diseases Intramural Research Program, under project
ZO1-DK043308. We are grateful to Hideko Takahashi and Huiyan Lu for
technical assistance with animal care, Satoshi Watanabe for technical
assistance with electron microscopy, Dr. Hisashi Hasumi and Dr. Masaya
Baba for valuable advice, and Dr. Kevin Bittman and Dr. Min Wu, both of
Seahorse Bioscience, for valuable advice in the design and
interpretation of particular experiments. We wish to thank Dr. Tom Leto
for a critical review of the manuscript.
NR 40
TC 15
Z9 16
U1 1
U2 6
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
PY 2013
VL 305
IS 10
BP F1477
EP F1490
DI 10.1152/ajprenal.00182.2013
PG 14
WC Physiology; Urology & Nephrology
SC Physiology; Urology & Nephrology
GA 257YU
UT WOS:000327424600011
PM 24049142
ER
PT J
AU Murphy, SC
Shott, JP
Parikh, S
Etter, P
Prescott, WR
Stewart, VA
AF Murphy, Sean C.
Shott, Joseph P.
Parikh, Sunil
Etter, Paige
Prescott, William R.
Stewart, V. Ann
TI Review Article: Malaria Diagnostics in Clinical Trials
SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
LA English
DT Review
ID POLYMERASE-CHAIN-REACTION; REAL-TIME PCR; PLASMODIUM-FALCIPARUM MALARIA;
HISTIDINE-RICH PROTEIN-2; MEDIATED ISOTHERMAL AMPLIFICATION;
SEQUENCE-BASED AMPLIFICATION; REVERSE TRANSCRIPTION PCR; PREGNANT-WOMEN;
ENDEMIC AREA; OPERATIONAL ACCURACY
AB Malaria diagnostics are widely used in epidemiologic studies to investigate natural history of disease and in drug and vaccine clinical trials to exclude participants or evaluate efficacy. The Malaria Laboratory Network (MLN), managed by the Office of HIV/AIDS Network Coordination, is an international working group with mutual interests in malaria disease and diagnosis and in human immunodeficiency virus/acquired immunodeficiency syndrome clinical trials. The MLN considered and studied the wide array of available malaria diagnostic tests for their suitability for screening trial participants and/or obtaining study endpoints for malaria clinical trials, including studies of HIV/malaria co-infection and other malaria natural history studies. The MLN provides recommendations on microscopy, rapid diagnostic tests, serologic tests, and molecular assays to guide selection of the most appropriate test(s) for specific research objectives. In addition, this report provides recommendations regarding quality management to ensure reproducibility across sites in clinical trials. Performance evaluation, quality control, and external quality assessment are critical processes that must be implemented in all clinical trials using malaria tests.
C1 [Murphy, Sean C.] Univ Washington, Dept Lab Med, Med Ctr, Seattle, WA 98195 USA.
[Shott, Joseph P.] NIAID, Div Intramural Res, NIH, Bethesda, MD 20892 USA.
Yale Univ, Sch Publ Hlth, New Haven, CT USA.
[Etter, Paige] Fred Hutchinson Canc Res Ctr, Off HIV AIDS Network Coordinat, Seattle, WA 98104 USA.
[Prescott, William R.] Hydas World Hlth, Hershey, PA USA.
[Stewart, V. Ann] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA.
RP Murphy, SC (reprint author), Univ Washington, Dept Lab Med, Med Ctr, Seattle, WA 98195 USA.
EM murphysc@uw.edu; shottj@mail.nih.gov; sunil.parikh@yale.edu;
petter@fhcrc.org; william.prescott@hydasworldhealth.org;
astewart@usuhs.edu
FU Office of HIV/AIDS Network Coordination Malaria Laboratory Network
[U01A1068614]; Division of Intramural Research, NIAID, NIH;
[1K08AI097238]; [R01HD068174]; [NO1-AI-85355]
FX The Office of HIV/AIDS Network Coordination Malaria Laboratory Network
is supported by grant U01A1068614. The authors are also supported by
grants 1K08AI097238 (Sean C. Murphy), R01HD068174 (Sunil Parikh), and
NO1-AI-85355 (William R. Prescott). Joseph P. Shott is supported by the
Division of Intramural Research, NIAID, NIH.
NR 134
TC 10
Z9 10
U1 0
U2 16
PU AMER SOC TROP MED & HYGIENE
PI MCLEAN
PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA
SN 0002-9637
EI 1476-1645
J9 AM J TROP MED HYG
JI Am. J. Trop. Med. Hyg.
PD NOV
PY 2013
VL 89
IS 5
BP 824
EP 839
DI 10.4269/ajtmh.12-0675
PG 16
WC Public, Environmental & Occupational Health; Tropical Medicine
SC Public, Environmental & Occupational Health; Tropical Medicine
GA 251BZ
UT WOS:000326904100003
PM 24062484
ER
PT J
AU Mejia, R
Nash, TE
AF Mejia, Rojelio
Nash, Theodore E.
TI Corticosteroid Withdrawal Precipitates Perilesional Edema around
Calcified Taenia solium Cysts
SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
LA English
DT Article
ID NEUROCYSTICERCOSIS LESIONS; STATUS-EPILEPTICUS; MRI ABNORMALITIES;
EPILEPTOGENESIS; FREQUENCY
AB Calcified Taenia solium granulomas are the focus of repeated episodes of perilesional edema and seizures in 50% of persons with calcifications, history of seizures, and a positive serology for cysticercosis. The pathophysiology is unclear but recent studies suggest the edema is caused by inflammation. We report two new cases and four other published cases where cessation of corticosteroids appeared to result in recurrence or new appearance of perilesional edema around calcifications. This suggests that perilesional edema is an immune-mediated phenomenon.
C1 NIAID, Helminth Immunol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
[Mejia, Rojelio] Baylor Coll Med, Natl Sch Trop Med, Houston, TX 77030 USA.
[Nash, Theodore E.] NIAID, Gastrointestinal Parasites Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
[Mejia, Rojelio; Nash, Theodore E.] NIAID, Parasit Dis Lab, Bethesda, MD 20892 USA.
RP Nash, TE (reprint author), NIAID, Gastrointestinal Parasites Sect, Parasit Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM rojelio.mejia@bcm.edu; tnash@niaid.nih.gov
FU National Institute of Allergy and Infectious Diseases; U.S. National
Institutes of Health
FX This study was supported by the Intramural Research Program of the
National Institute of Allergy and Infectious Diseases; U.S. National
Institutes of Health.
NR 24
TC 8
Z9 8
U1 0
U2 2
PU AMER SOC TROP MED & HYGIENE
PI MCLEAN
PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA
SN 0002-9637
EI 1476-1645
J9 AM J TROP MED HYG
JI Am. J. Trop. Med. Hyg.
PD NOV
PY 2013
VL 89
IS 5
BP 919
EP 923
DI 10.4269/ajtmh.13-0350
PG 5
WC Public, Environmental & Occupational Health; Tropical Medicine
SC Public, Environmental & Occupational Health; Tropical Medicine
GA 251BZ
UT WOS:000326904100016
PM 24002482
ER
PT J
AU Duncan, K
Rosean, TR
Tompkins, VS
Olivier, A
Sompallae, R
Zhan, F
Tricot, G
Acevedo, MR
Ponto, LLB
Walsh, SA
Tygrett, LT
Berger, AJ
Waldschmidt, T
Morse, HC
Sunderland, JJ
Janz, S
AF Duncan, K.
Rosean, T. R.
Tompkins, V. S.
Olivier, A.
Sompallae, R.
Zhan, F.
Tricot, G.
Acevedo, M. R.
Ponto, L. L. B.
Walsh, S. A.
Tygrett, L. T.
Berger, A. J.
Waldschmidt, T.
Morse, H. C., III
Sunderland, J. J.
Janz, S.
TI F-18-FDG-PET/CT imaging in an IL-6-and MYC-driven mouse model of human
multiple myeloma affords objective evaluation of plasma cell tumor
progression and therapeutic response to the proteasome inhibitor
ixazomib
SO BLOOD CANCER JOURNAL
LA English
DT Article
DE GEMM (genetically engineered mouse model) of human cancer; preclinical
cancer drug testing; plasma cell neoplasia
ID POSITRON-EMISSION-TOMOGRAPHY; CONTRAST-ENHANCED MRI; B-CELL; C-MYC;
ANTITUMOR-ACTIVITY; TRANSGENIC MICE; BONE-DISEASE; FDG PET/CT;
MALIGNANCIES; EXPRESSION
AB F-18-fluorodeoxyglucose positron emission tomography (FDG-PET) and computed tomography (CT) are useful imaging modalities for evaluating tumor progression and treatment responses in genetically engineered mouse models of solid human cancers, but the potential of integrated FDG-PET/CT for assessing tumor development and new interventions in transgenic mouse models of human blood cancers such as multiple myeloma (MM) has not been demonstrated. Here we use BALB/c mice that contain the newly developed iMyc(Delta E mu) gene insertion and the widely expressed H2-L-d-IL6 transgene to demonstrate that FDG-PET/CT affords an excellent research tool for assessing interleukin-6- and MYC-driven plasma cell tumor (PCT) development in a serial, reproducible and stage-and lesion-specific manner. We also show that FDG-PET/CT permits determination of objective drug responses in PCT-bearing mice treated with the investigational proteasome inhibitor ixazomib (MLN2238), the biologically active form of ixazomib citrate (MLN9708), that is currently in phase 3 clinical trials in MM. Overall survival of 5 of 6 ixazomib-treated mice doubled compared with mice left untreated. One outlier mouse presented with primary refractory disease. Our findings demonstrate the utility of FDG-PET/CT for preclinical MM research and suggest that this method will play an important role in the design and testing of new approaches to treat myeloma.
C1 [Duncan, K.; Rosean, T. R.; Tompkins, V. S.; Olivier, A.; Sompallae, R.; Tygrett, L. T.; Waldschmidt, T.; Janz, S.] Univ Iowa, Roy J & Lucille A Carver Coll Med, Dept Pathol, Iowa City, IA 52242 USA.
[Rosean, T. R.] Univ Iowa, Roy J & Lucille A Carver Coll Med, Interdisciplinary Immunol Grad Program, Iowa City, IA 52242 USA.
[Sompallae, R.] Univ Iowa, Roy J & Lucille A Carver Coll Med, Bioinformat Core Facil, Iowa City, IA 52242 USA.
[Zhan, F.; Tricot, G.] Univ Iowa, Roy J & Lucille A Carver Coll Med, Dept Internal Med, Iowa City, IA 52242 USA.
[Acevedo, M. R.; Ponto, L. L. B.; Walsh, S. A.; Sunderland, J. J.] Univ Iowa, Roy J & Lucille A Carver Coll Med, Dept Radiol, Iowa City, IA 52242 USA.
[Berger, A. J.] Takeda Pharmaceut Co Ltd, Cambridge, MA USA.
[Morse, H. C., III] NIAID, Virol & Cellular Immunol Sect, Immunogenet Lab, NIH, Rockville, MD USA.
RP Sunderland, JJ (reprint author), Univ Iowa, Roy J & Lucille A Carver Coll Med, Dept Radiol, 3881 JPP, Iowa City, IA 52242 USA.
EM john-sunderland@uiowa.edu; siegfried-janz@uiowa.edu
OI Morse, Herbert/0000-0002-9331-3705; Tompkins, Van/0000-0003-1279-8075
FU Intramural Research Program of the NIAID; NCI core Grant of The
University of Iowa Holden Comprehensive Cancer Center (HCCC)
[P30CA086862]; Oberley Research Grant from HCCC; Multiple Myeloma
Research Foundation; International Waldenstrom's Macroglobulinemia
Foundation; NCI [R01CA151354]
FX This research was performed by KD in partial fulfillment of the
requirements for the Degree Master of Sciences in the Graduate Program
of the University of Iowa Department of Pathology. We thank Ling Hu for
expert mouse husbandry. This work was supported in part by the
Intramural Research Program of the NIAID (to HCM), by NCI core Grant
P30CA086862 in support of The University of Iowa Holden Comprehensive
Cancer Center (HCCC), by an Oberley Research Grant from HCCC (to JJS),
by research awards from the Multiple Myeloma Research and International
Waldenstrom's Macroglobulinemia Foundations (to SJ) and by R01CA151354
from the NCI (to SJ).
NR 52
TC 14
Z9 14
U1 0
U2 7
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2044-5385
J9 BLOOD CANCER J
JI Blood Cancer J.
PD NOV
PY 2013
VL 3
AR UNSP e165
DI 10.1038/bcj.2013.61
PG 12
WC Oncology
SC Oncology
GA 267BO
UT WOS:000328069400011
PM 24292417
ER
PT J
AU Makarova, KS
Koonin, EV
AF Makarova, Kira S.
Koonin, Eugene V.
TI Archaeology of Eukaryotic DNA Replication
SO COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY
LA English
DT Article
ID OKAZAKI FRAGMENT MATURATION; GINS COMPLEX; POLYMERASE-ALPHA; STRUCTURAL
BASIS; CELL-CYCLE; SULFOLOBUS-SOLFATARICUS; EVOLUTIONARY HISTORY;
FUNCTIONAL-ANALYSIS; CATALYTIC SUBUNIT; CONSERVED DOMAINS
AB Recent advances in the characterization of the archaeal DNA replication system together with comparative genomic analysis have led to the identification of several previously un-characterized archaeal proteins involved in replication and currently reveal a nearly complete correspondence between the components of the archaeal and eukaryotic replication machineries. It can be inferred that the archaeal ancestor of eukaryotes and even the last common ancestor of all extant archaea possessed replication machineries that were comparable in complexity to the eukaryotic replication system. The eukaryotic replication system encompasses multiple paralogs of ancestral components such that heteromeric complexes in eukaryotes replace archaeal homomeric complexes, apparently along with subfunctionalization of the eukaryotic complex subunits. In the archaea, parallel, lineage-specific duplications of many genes encoding replication machinery components are detectable as well; most of these archaeal paralogs remain to be functionally characterized. The archaeal replication system shows remarkable plasticity whereby even some essential components such as DNA polymerase and single-stranded DNA-binding protein are displaced by unrelated proteins with analogous activities in some lineages.
C1 [Makarova, Kira S.; Koonin, Eugene V.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
RP Koonin, EV (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
EM koonin@ncbi.nlm.nih.gov
FU U.S. Department of Health and Human Services
FX The authors' research is supported by the intramural funds of the U.S.
Department of Health and Human Services (to the National Library of
Medicine).
NR 116
TC 16
Z9 17
U1 1
U2 11
PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
PI COLD SPRING HARBOR
PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA
SN 1943-0264
J9 CSH PERSPECT BIOL
JI Cold Spring Harbor Perspect. Biol.
PD NOV
PY 2013
VL 5
IS 11
AR a012963
DI 10.1101/cshperspect.a012963
PG 25
WC Cell Biology
SC Cell Biology
GA 262NN
UT WOS:000327742400006
PM 23881942
ER
PT J
AU Traub, LM
Bonifacino, JS
AF Traub, Linton M.
Bonifacino, Juan S.
TI Cargo Recognition in Clathrin-Mediated Endocytosis
SO COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY
LA English
DT Article
ID DENSITY-LIPOPROTEIN RECEPTOR; AP-3 ADAPTER COMPLEX; VIRUS TYPE-1 NEF;
DI-LEUCINE MOTIF; PHOSPHOTYROSINE-BINDING DOMAIN; POLARIZED
EPITHELIAL-CELLS; SENSORY ORGAN PRECURSOR; ADP-RIBOSYLATION FACTOR;
GROWTH-FACTOR RECEPTOR; FATE DETERMINANT NUMB
AB The endosomal system is expansive and complex, characterized by swift morphological transitions, dynamic remodeling of membrane constituents, and intracellular positioning changes. To properly navigate this ever-altering membrane labyrinth, transmembrane protein cargoes typically require specific sorting signals that are decoded by components of protein coats. The best-characterized sorting process within the endosomal system is the rapid internalization of select transmembrane proteins within clathrin-coated vesicles. Endocytic signals consist of linear motifs, conformational determinants, or covalent modifications in the cytosolic domains of transmembrane cargo. These signals are interpreted by a diverse set of clathrin-associated sorting proteins (CLASPs) that translocate from the cytosol to the inner face of the plasma membrane. Signal recognition by CLASPs is highly cooperative, involving additional interactions with phospholipids, Arf GTPases, other CLASPs, and clathrin, and is regulated by large conformational changes and covalent modifications. Related sorting events occur at other endosomal sorting stations.
C1 [Traub, Linton M.] Univ Pittsburgh, Sch Med, Dept Cell Biol, Pittsburgh, PA 15261 USA.
[Bonifacino, Juan S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Metab Program, NIH, Bethesda, MD 20892 USA.
RP Traub, LM (reprint author), Univ Pittsburgh, Sch Med, Dept Cell Biol, Pittsburgh, PA 15261 USA.
EM traub@pitt.edu
OI Bonifacino, Juan S./0000-0002-5673-6370
FU National Institutes of Health (NIH) [R01 DK53249]; NICHD, NIH
FX L.M.T. is supported by the extramural program of National Institutes of
Health (NIH) (R01 DK53249). J.S.B. is supported by the intramural
program of NICHD, NIH. We are grateful to Bertram Canagarajah, John
Guatelli, Jim Hurley, David Owen, Xuefeng Ren, and Yong Xiong for
providing atomic coordinate files.
NR 196
TC 47
Z9 47
U1 3
U2 20
PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
PI COLD SPRING HARBOR
PA 1 BUNGTOWN RD, COLD SPRING HARBOR, NY 11724 USA
SN 1943-0264
J9 CSH PERSPECT BIOL
JI Cold Spring Harbor Perspect. Biol.
PD NOV
PY 2013
VL 5
IS 11
AR a016790
DI 10.1101/cshperspect.a016790
PG 23
WC Cell Biology
SC Cell Biology
GA 262NN
UT WOS:000327742400007
PM 24186068
ER
PT J
AU Chan, K
Resnick, MA
Gordenin, DA
AF Chan, Kin
Resnick, Michael A.
Gordenin, Dmitry A.
TI The choice of nucleotide inserted opposite abasic sites formed within
chromosomal DNA reveals the polymerase activities participating in
translesion DNA synthesis
SO DNA REPAIR
LA English
DT Article
DE Abasic site; Translesion DNA synthesis; APOBEC; Single-strand DNA;
Deoxycytidyltransferase
ID THYMINE-THYMINE DIMER; YEAST REV1 PROTEIN; SACCHAROMYCES-CEREVISIAE;
INDUCED MUTAGENESIS; POL-ETA; TRANSFERASE-ACTIVITY; ACCESSORY SUBUNITS;
ESCHERICHIA-COLI; DCMP TRANSFERASE; IN-VIVO
AB Abasic sites in genomic DNA can be a significant source of mutagenesis in biological systems, including human cancers. Such mutagenesis requires translesion DNA synthesis (TLS) bypass of the abasic site by specialized DNA polymerases. The abasic site bypass specificity of TLS proteins had been studied by multiple means in vivo and in vitro, although the generality of the conclusions reached have been uncertain. Here, we introduce a set of yeast reporter strains for investigating the in vivo specificity of abasic site bypass at numerous random positions within chromosomal DNA. When shifted to 37 degrees C, these strains underwent telomere uncapping and resection that exposed reporter genes within a long 3' ssDNA overhang. Human APOBEC3G cytosine deaminase was expressed to create uracils in ssDNA, which were excised by uracil-DNA N-glycosylase. During repair synthesis, error-prone TLS bypassed the resulting abasic sites. Because of APOBEC3G's strict motif specificity and the restriction of abasic site formation to only one DNA strand, this system provides complete information about the location of abasic sites that led to mutations. We recapitulated previous findings on the roles of REV1 and REV3. Further, we found that sequence context can strongly influence the relative frequency of A or C insertion. We also found that deletion of Pol32, a non-essential common subunit of Pols delta and zeta, resulted in residual low-frequency C insertion dependent on Rev1 catalysis. We summarize our results in a detailed model of the interplay between TLS components leading to error-prone bypass of abasic sites. Our results underscore the utility of this system for studying TLS bypass of many types of lesions within genomic DNA. Published by Elsevier B.V.
C1 [Chan, Kin; Resnick, Michael A.; Gordenin, Dmitry A.] NIEHS, Chromosome Stabil Sect, Mol Genet Lab, NIH, Res Triangle Pk, NC 27709 USA.
RP Gordenin, DA (reprint author), 111 TW Alexander Dr,POB 12233, Res Triangle Pk, NC 27709 USA.
EM chank2@niehs.nih.gov; resnick@niehs.nih.gov; gordenin@niehs.nih.gov
OI Gordenin, Dmitry/0000-0002-8399-1836
FU National Institute of Environmental Health Sciences (NIH, DHHS)
[E5065073]
FX We thank Drs. T.A. Kunkel, D.R. Menendez, T.T. Nguyen, and S.A. Roberts
for critical reading of the manuscript. This work was supported by the
Intramural Research Program of the National Institute of Environmental
Health Sciences (NIH, DHHS) project E5065073 to MAR.
NR 71
TC 20
Z9 20
U1 1
U2 7
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1568-7864
EI 1568-7856
J9 DNA REPAIR
JI DNA Repair
PD NOV
PY 2013
VL 12
IS 11
BP 878
EP 889
DI 10.1016/j.dnarep.2013.07.008
PG 12
WC Genetics & Heredity; Toxicology
SC Genetics & Heredity; Toxicology
GA 260FA
UT WOS:000327579200004
PM 23988736
ER
PT J
AU Kodama, S
Negishi, M
AF Kodama, Susumu
Negishi, Masahiko
TI Sulfotransferase genes: Regulation by nuclear receptors in response to
xeno/endo-biotics
SO DRUG METABOLISM REVIEWS
LA English
DT Review
DE Constitutive active/androstane receptor; gene regulation; pregnane X
receptor; sulfotransferase; xeno-sensing nuclear receptor
ID PREGNANE-X-RECEPTOR; CONSTITUTIVE-ANDROSTANE RECEPTOR; THYROID-HORMONE
METABOLISM; BILE-ACID METABOLISM; VITAMIN-D-RECEPTOR;
DEHYDROEPIANDROSTERONE SULFOTRANSFERASE; ESTROGEN SULFOTRANSFERASE;
CYTOSOLIC SULFOTRANSFERASES; STEROID SULFATASE; MOUSE-LIVER
AB Pregnane X receptor (PXR) and constitutive active/androstane receptor (CAR), members of the nuclear receptor superfamily, are two major xeno-sensing transcription factors. They can be activated by a broad range of lipophilic xenobiotics including therapeutics drugs. In addition to xenobiotics, endogenous compounds such as steroid hormones and bile acids can also activate PXR and/or CAR. These nuclear receptors regulate genes that encode enzymes and transporters that metabolize and excrete both xenobiotics and endobiotics. Sulfotransferases (SULTs) are a group of these enzymes and sulfate xenobiotics for detoxification. In general, inactivation by sulfation constitutes the mechanism to maintain homeostasis of endobiotics. Thus, deciphering the molecular mechanism by which PXR and CAR regulate SULT genes is critical for understanding the roles of SULTs in the alterations of physiological and pathophysiological processes caused by drug treatment or environmental exposures.
C1 [Kodama, Susumu] Tohoku Univ, Grad Sch Pharmaceut Sci, Div Drug Metab & Mol Toxicol, Sendai, Miyagi 980, Japan.
[Negishi, Masahiko] NIEHS, Pharmacogenet Sect, Lab Reprod & Dev Toxicol, NIH, Res Triangle Pk, NC 27709 USA.
RP Negishi, M (reprint author), NIEHS, Pharmacogenet Sect, Lab Reprod & Dev Toxicol, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
EM negishi@niehs.nih.gov
FU Japan Society for the Promotion of Science [24790142]; National
Institutes of Health, and National Institute of Environmental Health
Sciences [Z01ES1005-01]
FX This work was supported by Grant-in-Aid for Young Scientists from Japan
Society for the Promotion of Science: 24790142 (S.K.) and by the
Intramural Research Program of the National Institutes of Health, and
National Institute of Environmental Health Sciences: Z01ES1005-01
(M.N.).
NR 119
TC 5
Z9 5
U1 1
U2 6
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 0360-2532
EI 1097-9883
J9 DRUG METAB REV
JI Drug Metab. Rev.
PD NOV
PY 2013
VL 45
IS 4
BP 441
EP 449
DI 10.3109/03602532.2013.835630
PG 9
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 266FQ
UT WOS:000328009200007
PM 24025090
ER
PT J
AU Gage, JC
Joste, N
Ronnett, BM
Stoler, M
Hunt, WC
Schiffman, M
Wheeler, CM
AF Gage, Julia C.
Joste, Nancy
Ronnett, Brigette M.
Stoler, Mark
Hunt, William C.
Schiffman, Mark
Wheeler, Cosette M.
CA New Mexico HPV Pap Registry Steeri
TI A comparison of cervical histopathology variability using whole slide
digitized images versus glass slides: experience with a statewide
registry
SO HUMAN PATHOLOGY
LA English
DT Article
DE Cervical intraepithelial neoplasia; Whole slide imaging; Clinical
pathology; Reliability; Registries
ID INTEROBSERVER VARIATION; INTRAEPITHELIAL NEOPLASIA; SURGICAL PATHOLOGY;
VIRTUAL MICROSCOPY; BIOPSY SPECIMENS; DIAGNOSIS; DYSPLASIA; AGREEMENT
AB Whole slide imaging is increasingly used for primary and consultative diagnoses, teaching, telepathology, slide sharing, and archiving. We compared pathologist evaluations of glass slides and corresponding digitized images within the context of a statewide surveillance effort. Cervical specimens collected by the New Mexico HPV Pap Registry research program targeted cases diagnosed between 2006 and 2010. Two samples of 250 slides each were digitized with the ScanScope XT (Aperio, Vista, CA) microscope and reviewed with Aperio ImageScope reader. (1) A "random set" had a distribution of community diagnoses: 70% from cases of cervical intraepithelial neoplasia grade 2 or higher, 20% from cases of cervical intraepithelial neoplasia grade 1 and 10% from negative cases. (2) A "discrepant set" was represented by difficult cases where 2 study pathologists initially disagreed. Within the regular workflow of the New Mexico HPV Pap Registry, 3 pathologists read the slides 2 to 3 times each without knowledge of clinical history, previous readings or sampling scheme. Pathologists also read each corresponding image twice. For within- and between-reader comparisons we calculated unweighted kappa statistics and asymmetry chi(2) tests. Across all comparisons, slides and images yielded similar results. For the random set, almost all within-reader and between-reader Kappa values ranged between 0.7 and 0.8 and 0.6 and 0.7, respectively. For the discrepant set, most within- and between-reader kappa values were 0.4 to 0.6. As cervical intraepithelial neoplasia diagnostic terminology changes, pathologists may need to reread histopathology slides to compare disease trends over time, eg, before/after introduction of human papillomavirus vaccination. Diagnosis of cervical intraepithelial neoplasia differed little between slides and corresponding digitized images. (C) 2013 Elsevier Inc. All rights reserved.
C1 [Gage, Julia C.; Schiffman, Mark] NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20850 USA.
[Joste, Nancy; Hunt, William C.; Wheeler, Cosette M.] Univ New Mexico, Hlth Sci Ctr, Dept Pathol, Ctr HPV Prevent, Albuquerque, NM 87131 USA.
[Ronnett, Brigette M.] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA.
[Ronnett, Brigette M.] Johns Hopkins Univ, Sch Med, Dept Gynecol & Obstet, Baltimore, MD 21205 USA.
[Stoler, Mark] Univ Virginia, Dept Pathol, Charlottesville, VA 22908 USA.
RP Wheeler, CM (reprint author), Univ New Mexico, Hlth Sci Ctr, Dept Pathol, House Prevent Epidemiol HOPE, Albuquerque, NM 87131 USA.
EM cwheeler@salud.unm.edu
FU Merck and Co, Inc; Glaxo SmithKline
FX C.M.W. has received funding through the University of New Mexico from
(1) Merck and Co, Inc, and Glaxo SmithKline for HPV vaccine studies and
travel reimbursements related to publication activities and (2)
equipment and reagents from Roche Molecular Systems for HPV genotyping.
Dr Schiffman and Dr Gage report working with Qiagen, Inc, on an
independent evaluation of non-commercial uses of CareHPV (a low-cost HPV
test for low-resource regions) for which they have received research
reagents and technical aid from Qiagen at no cost. They have received
HPV testing for research at no cost from Roche. The other authors report
no conflicts of interest.
NR 24
TC 8
Z9 8
U1 0
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 0046-8177
EI 1532-8392
J9 HUM PATHOL
JI Hum. Pathol.
PD NOV
PY 2013
VL 44
IS 11
BP 2542
EP 2548
DI 10.1016/j.humpath.2013.06.015
PG 7
WC Pathology
SC Pathology
GA 261SB
UT WOS:000327683800021
PM 24075599
ER
PT J
AU Nugent, LF
Shi, GP
Vistica, BP
Ogbeifun, O
Hinshaw, SJH
Gery, I
AF Nugent, Lindsey F.
Shi, Guangpu
Vistica, Barbara P.
Ogbeifun, Osato
Hinshaw, Samuel J. H.
Gery, Igal
TI ITE, A Novel Endogenous Nontoxic Aryl Hydrocarbon Receptor Ligand,
Efficiently Suppresses EAU and T-Cell-Mediated Immunity
SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
LA English
DT Article
DE aryl hydrocarbon receptor ligand; experimental autoimmune uveitis;
T-cell mediated immunity
ID EXPERIMENTAL AUTOIMMUNE UVEORETINITIS; CYTOKINE GM-CSF; INFLAMMATION;
DIFFERENTIATION; ACTIVATION; MECHANISMS; UVEITIS
AB PURPOSE. Ligands for aryl hydrocarbon receptor (AHR), such as dioxins, are highly toxic. One such ligand, TCDD, was found to exert potent immunosuppressive capacities in mice developing pathogenic autoimmune processes, including EAU, but its toxicity makes it unusable for humans. A recently identified endogenous AHR ligand, ITE, is also immunosuppressive, but is nontoxic and could therefore be useful for therapy in humans. Here, we tested ITE for its capacity to inhibit EAU and related immune responses.
METHODS. EAU was induced in B10. A mice by immunization with interphotoreceptor retinoid-binding protein (IRBP; 40 mu g) in CFA. Treatment with ITE was by daily intraperitoneal injection of 0.2 mg. Disease severity was assessed by both fundoscopy and histological examination. Draining lymph node cells were tested for proliferation by thymidine uptake and for cytokine production and release by ELISA. In addition, the intracellular expression of cytokines and Foxp3 was determined by flow cytometry. Serum antibodies were measured by ELISA.
RESULTS. Treatment with ITE efficiently inhibited the development of EAU in mice, as well as the cellular immune responses against IRBP and PPD. ITE treatment inhibited the expansion of both Th1 and Th17 subpopulations, as well as their release of the signature cytokines, IFNgamma and IL-17. The treatment moderately increased, however, the proportion of Foxp3 expressing T-regulatory cells. Antibody production was not affected by the treatment.
CONCLUSIONS. ITE, an endogenous AHR ligand, efficiently inhibits EAU development and related cellular immune responses. Being nontoxic, ITE may be considered for treatment of pathogenic immunity in humans.
C1 [Nugent, Lindsey F.; Shi, Guangpu; Vistica, Barbara P.; Ogbeifun, Osato; Hinshaw, Samuel J. H.; Gery, Igal] NEI, Expt Immunol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA.
RP Gery, I (reprint author), NEI, Lab Immunol, NIH, Bldg 10,Room 10N208, Bethesda, MD 20892 USA.
EM geryi@nei.nih.gov
FU Intramural Research Program of the National Eye Institute, National
Institutes of Health
FX Supported by the Intramural Research Program of the National Eye
Institute, National Institutes of Health.
NR 25
TC 5
Z9 6
U1 0
U2 8
PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC
PI ROCKVILLE
PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA
SN 0146-0404
EI 1552-5783
J9 INVEST OPHTH VIS SCI
JI Invest. Ophthalmol. Vis. Sci.
PD NOV
PY 2013
VL 54
IS 12
BP 7463
EP 7469
DI 10.1167/iovs.12-11479
PG 7
WC Ophthalmology
SC Ophthalmology
GA 265KH
UT WOS:000327949700037
PM 24150760
ER
PT J
AU Sadowsky, CL
Hammond, ER
Strohl, AB
Commean, PK
Eby, SA
Damiano, DL
Wingert, JR
Bae, KT
McDonald, JW
AF Sadowsky, Cristina L.
Hammond, Edward R.
Strohl, Adam B.
Commean, Paul K.
Eby, Sarah A.
Damiano, Diane L.
Wingert, Jason R.
Bae, Kyongtae T.
McDonald, John W., III
TI Lower extremity functional electrical stimulation cycling promotes
physical and functional recovery in chronic spinal cord injury
SO JOURNAL OF SPINAL CORD MEDICINE
LA English
DT Article
DE Spinal cord injury; Activity-based restorative therapy; Functional
electrical stimulation; Rehabilitation; Cycle ergometry; Assistive
technology; Paraplegia; Tetraplegia; Rehabilitation; Physical muscle
strength; Spasticity; Quality of life
ID RESTORING FUNCTION; PROGENITOR CELLS; BODY-COMPOSITION; STEM-CELLS;
INDIVIDUALS; REGENERATION; THERAPY; REHABILITATION
AB Objective: To examine the effect of long-termlower extremity functional electrical stimulation (FES) cycling on the physical integrity and functional recovery in people with chronic spinal cord injury (SCI).
Design: Retrospective cohort, mean follow-up 29.1 months, and cross-sectional evaluation.
Setting: Washington University Spinal Cord Injury Neurorehabilitation Center, referral center.
Participants: Twenty-five people with chronic SCI who received FES during cycling were matched by age, gender, injury level, and severity, and duration of injury to 20 people with SCI who received range of motion and stretching.
Intervention: Lower extremity FES during cycling as part of an activity-based restorative treatment regimen.
Main outcome measure: Change in neurological function: motor, sensory, and combined motor-sensory scores (CMSS) assessed by the American Spinal Injury Association Impairment scale. Response was defined as >= 1 point improvement.
Results: FES was associated with an 80% CMSS responder rate compared to 40% in controls. An average 9.6 CMSS point loss among controls was offset by an average 20-point gain among FES subjects. Quadriceps muscle mass was on average 36% higher and intra/inter-muscular fat 44% lower, in the FES group. Hamstring and quadriceps muscle strength was 30 and 35% greater, respectively, in the FES group. Quality of life and daily function measures were significantly higher in FES group.
Conclusion: FES during cycling in chronic SCI may provide substantial physical integrity benefits, including enhanced neurological and functional performance, increased muscle size and force-generation potential, reduced spasticity, and improved quality of life.
C1 [Sadowsky, Cristina L.; Hammond, Edward R.; McDonald, John W., III] Int Ctr Spinal Cord Injury, Baltimore, MD USA.
[Sadowsky, Cristina L.; Hammond, Edward R.; McDonald, John W., III] Kennedy Krieger, Hugo W Moser Res Inst, Baltimore, MD USA.
[Sadowsky, Cristina L.] Dept Neurol JWM, Dept Phys Med & Rehabil, Baltimore, MD USA.
[Strohl, Adam B.] Mt Sinai Med Ctr, Div Plast & Reconstruct Surg, New York, NY USA.
[Commean, Paul K.] Washington Univ, Sch Med, Mallinckrodt Inst Radiol, St Louis, MO USA.
[Eby, Sarah A.] Sinai Hosp, Dept Phys Med & Rehabil, Baltimore, MD 21215 USA.
[Damiano, Diane L.] NIH, Bethesda, MD 20892 USA.
[Wingert, Jason R.] Univ N Carolina, Dept Hlth & Wellness, Asheville, NC 28804 USA.
[Bae, Kyongtae T.] Univ Pittsburgh, Sch Med, Dept Radiol, Pittsburgh, PA USA.
[McDonald, John W., III] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA.
RP McDonald, JW (reprint author), Kennedy Krieger Inst, Int Ctr Spinal Cord Injury, 716 North Broadway,4th Floor, Baltimore, MD 21205 USA.
EM mcdonaldj@kennedykrieger.org
RI Damiano, Diane/B-3338-2010
OI Damiano, Diane/0000-0002-2770-5356
FU Deans Fund at Washington University School of Medicine; Barnes-Jewish
Hospital Foundation; Barnes-Jewish Hospital Auxiliary Foundation;
Christopher Reeve Paralysis Foundation (C.S.); Nextsteps Foundation (St.
Louis, MO); Sam Schmidt Foundation (Las Vegas, NV; C.S.); Gateway to a
Cure Foundation (St. Louis, MO); Eric Westacott Foundation (St. Louis,
MO); Intramural Research Program at the NIH Clinical Center
FX This work was supported by funding from the Deans Fund at Washington
University School of Medicine (J.W.M.), Barnes-Jewish Hospital
Foundation (J.W.M.), the Barnes-Jewish Hospital Auxiliary Foundation
(J.W.M.), Christopher Reeve Paralysis Foundation (C.S., J.W.M.), the
Nextsteps Foundation (St. Louis, MO; J.W.M.), the Sam Schmidt Foundation
(Las Vegas, NV; C.S., J.W.M.), Gateway to a Cure Foundation (St. Louis,
MO; J.W.M.), and the Eric Westacott Foundation (St. Louis, MO; J.W.M.)
and, in part, by the Intramural Research Program at the NIH Clinical
Center. Our appreciation to Anna Schneider for technical assistance.
Author J.W.M. had full access to all the data in the study and takes
responsibility for the integrity of the data and the accuracy of the
data analysis.
NR 40
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U1 1
U2 24
PU MANEY PUBLISHING
PI LEEDS
PA STE 1C, JOSEPHS WELL, HANOVER WALK, LEEDS LS3 1AB, W YORKS, ENGLAND
SN 1079-0268
EI 2045-7723
J9 J SPINAL CORD MED
JI J. Spinal Cord. Med.
PD NOV
PY 2013
VL 36
IS 6
BP 623
EP 631
DI 10.1179/2045772313Y.0000000101
PG 9
WC Clinical Neurology
SC Neurosciences & Neurology
GA 264JC
UT WOS:000327871900007
PM 24094120
ER
PT J
AU Merino, JG
Luby, M
Benson, RT
Davis, LA
Hsia, AW
Latour, LL
Lynch, JK
Warach, S
AF Merino, Jose G.
Luby, Marie
Benson, Richard T.
Davis, Lisa A.
Hsia, Amie W.
Latour, Lawrence L.
Lynch, John K.
Warach, Steven
TI Predictors of Acute Stroke Mimics in 8187 Patients Referred to a Stroke
Service
SO JOURNAL OF STROKE & CEREBROVASCULAR DISEASES
LA English
DT Article
DE Acute stroke; emergency medicine; stroke mimics; diagnosis
ID EMERGENCY; CARE; OUTCOMES; TRIALS; SAFETY
AB Background: Some patients seen by a stroke team do not have cerebrovascular disease but a condition that mimics stroke. The purpose of this study was to determine the rate and predictors of stroke mimics in a large sample. Methods: This is an analysis of data from consecutive patients seen by the National Institutes of Health Stroke Program over 10 years. Data were collected prospectively as a quality improvement initiative. Patients with a cerebrovascular event or a stroke mimic were compared with the Student t or Pearson chi-square test as appropriate, and logistic regression was done to identify independent predictors. Results: The analysis included 8187 patients: 30% had a stroke mimic. Patients with a stroke mimic were younger, and the proportion of patients with a stroke mimic was higher among women, patients without any risk factors, those seen as a code stroke or who arrived to the emergency department via personal vehicle, and those who had the onset of symptoms while inpatients. The proportion of patients with a stroke mimic was marginally higher among African-Americans than Caucasians. Factors associated with the greatest odds of having a stroke mimic in the logistic regression were lack of a history of hypertension, atrial fibrillation or hyperlipidemia. Conclusions: One third of the patients seen by a stroke team over 10 years had a stroke mimic. Factors associated with a stroke mimic may be ascertained by an emergency physician before calling the stroke team.
C1 [Merino, Jose G.; Luby, Marie; Benson, Richard T.; Davis, Lisa A.; Hsia, Amie W.; Latour, Lawrence L.; Lynch, John K.; Warach, Steven] NINDS, Sect Stroke Diagnost & Therapeut, Bethesda, MD 20892 USA.
[Merino, Jose G.] Johns Hopkins Community Phys, Bethesda, MD 20814 USA.
[Merino, Jose G.] Suburban Hosp Stroke Ctr, Bethesda, MD USA.
[Benson, Richard T.; Hsia, Amie W.] Medstar Washington Hosp Ctr, Stroke Ctr, Washington, DC USA.
[Warach, Steven] Seton UT Southwestern Clin Res Inst, Austin, TX USA.
RP Merino, JG (reprint author), Johns Hopkins Community Phys, 7315 Wisconsin Ave,Suite 700, Bethesda, MD 20814 USA.
EM jmerino3@jhmi.edu
OI Merino, Jose/0000-0002-6676-0008
FU Division of Intramural Research of the National Institute of
Neurological Disorders and Stroke of the National Institutes of Health
FX The Division of Intramural Research of the National Institute of
Neurological Disorders and Stroke of the National Institutes of Health
supported this research.
NR 16
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U1 0
U2 1
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1052-3057
EI 1532-8511
J9 J STROKE CEREBROVASC
JI J. Stroke Cerebrovasc. Dis.
PD NOV
PY 2013
VL 22
IS 8
BP E397
EP E403
DI 10.1016/j.jstrokecerebrovasdis.2013.04.018
PG 7
WC Neurosciences; Peripheral Vascular Disease
SC Neurosciences & Neurology; Cardiovascular System & Cardiology
GA 262FF
UT WOS:000327719000021
PM 23680681
ER
PT J
AU Crooks, DR
Natarajan, TG
Chen, CM
Huang, HZ
Ghosh, MC
Tong, WH
Haller, RG
Wu, C
Rouault, TA
AF Crooks, Daniel R.
Natarajan, Thanemozhi G.
Chen, Chuming
Huang, Hongzhan
Ghosh, Manik C.
Tong, Wing-Hang
Haller, Ronald G.
Wu, Cathy
Rouault, Tracey A.
TI FGF-21 secretion and ketogenic enzyme expression are hallmarks of
chronic energy deficiency in human skeletal muscles depleted of iron
sulfur clusters
SO MITOCHONDRION
LA English
DT Meeting Abstract
C1 [Crooks, Daniel R.; Natarajan, Thanemozhi G.; Wu, Cathy] Georgetown Univ, Med Ctr, Dept Biochem Mol & Cellular Biol, Washington, DC 20057 USA.
[Crooks, Daniel R.; Ghosh, Manik C.; Tong, Wing-Hang; Rouault, Tracey A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Mol Med Program, Bethesda, MD 20892 USA.
[Chen, Chuming; Huang, Hongzhan; Wu, Cathy] Univ Delaware, Ctr Bioinformat & Computat Biol, Newark, DE 19711 USA.
[Haller, Ronald G.] Univ Texas SW Med Ctr Dallas, Dept Neurol, Dallas, TX 75231 USA.
[Haller, Ronald G.] VA North Texas Med Ctr, Dallas, TX 75231 USA.
[Haller, Ronald G.] Neuromuscular Ctr, Inst Exercise & Environm Med, Dallas, TX 75231 USA.
NR 0
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U1 0
U2 1
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1567-7249
EI 1872-8278
J9 MITOCHONDRION
JI Mitochondrion
PD NOV
PY 2013
VL 13
IS 6
MA 18
BP 904
EP 904
DI 10.1016/j.mito.2013.07.018
PG 1
WC Cell Biology; Genetics & Heredity
SC Cell Biology; Genetics & Heredity
GA 255ZY
UT WOS:000327280500058
ER
PT J
AU Young, MJ
Sun, KY
Humble, MM
Copeland, WC
AF Young, Matthew J.
Sun, Kathie Y.
Humble, Maggie M.
Copeland, William C.
TI The complexity of heterozygous POLG2 mutations associated with human
mitochondrial disease
SO MITOCHONDRION
LA English
DT Meeting Abstract
C1 [Young, Matthew J.; Humble, Maggie M.; Copeland, William C.] NIEHS, NIH, Res Triangle Pk, NC 27709 USA.
[Sun, Kathie Y.] NHGRI, NIH, Bethesda, MD 20892 USA.
NR 0
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U1 0
U2 0
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 2013
VL 13
IS 6
MA 91
BP 930
EP 930
DI 10.1016/j.mito.2013.07.084
PG 1
WC Cell Biology; Genetics & Heredity
SC Cell Biology; Genetics & Heredity
GA 255ZY
UT WOS:000327280500124
ER
PT J
AU Milena, P
Pickrell, AM
Youle, RJ
Moraes, CT
AF Milena, Pinto
Pickrell, Alicia M.
Youle, Richard J.
Moraes, Carlos T.
TI The role of Parkin in the clearance of defective mitochondria with
deleted mtDNA in the CNS
SO MITOCHONDRION
LA English
DT Meeting Abstract
C1 [Milena, Pinto; Moraes, Carlos T.] Univ Miami, Miller Sch Med, Dept Neurol, Miami, FL 33136 USA.
[Pickrell, Alicia M.; Youle, Richard J.] NINDS, Biochem Sect, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA.
[Moraes, Carlos T.] Univ Miami, Miller Sch Med, Neurosci Grad Program, Miami, FL 33136 USA.
NR 0
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Z9 0
U1 0
U2 3
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 2013
VL 13
IS 6
MA 103
BP 935
EP 935
DI 10.1016/j.mito.2013.07.095
PG 1
WC Cell Biology; Genetics & Heredity
SC Cell Biology; Genetics & Heredity
GA 255ZY
UT WOS:000327280500135
ER
PT J
AU Wolfe, LA
Regier, D
Saneto, R
Parikh, S
Goldstein, A
Boerkorl, N
AF Wolfe, Lynne A.
Regier, Debra
Saneto, Russell
Parikh, Sumit
Goldstein, Amy
Boerkorl, Neal
TI Failure to thrive in children with mitochondrial diseases
SO MITOCHONDRION
LA English
DT Meeting Abstract
C1 [Wolfe, Lynne A.; Regier, Debra; Boerkorl, Neal] NHGRI, Undiag Dis Program, Bethesda, MD 20892 USA.
[Regier, Debra] Childrens Natl Med Ctr, Washington, DC 20010 USA.
[Saneto, Russell] Neurol Seattle, Seattle, WA USA.
[Parikh, Sumit] Neurosci Cleveland Clin, Cleveland, OH USA.
[Goldstein, Amy] UPMC, Div Pediat Neurol, Dept Pediat, Childrens Hosp, Pittsburgh, PA USA.
NR 0
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U1 0
U2 0
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 2013
VL 13
IS 6
MA 102
BP 935
EP 935
DI 10.1016/j.mito.2013.07.094
PG 1
WC Cell Biology; Genetics & Heredity
SC Cell Biology; Genetics & Heredity
GA 255ZY
UT WOS:000327280500134
ER
PT J
AU Pickrell, AM
Huang, CH
Pinto, M
Moraes, CT
Youle, RJ
AF Pickrell, Alicia M.
Huang, Chiu-Hui
Pinto, Milena
Moraes, Carlos T.
Youle, Richard J.
TI Therapy for mitochondrial diseases: An investigation into the potential
to stimulate Parkin-mediated mitophagy
SO MITOCHONDRION
LA English
DT Meeting Abstract
C1 [Pickrell, Alicia M.; Huang, Chiu-Hui; Pinto, Milena; Moraes, Carlos T.; Youle, Richard J.] NINDS, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 3
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 2013
VL 13
IS 6
MA 123
BP 943
EP 943
DI 10.1016/j.mito.2013.07.111
PG 1
WC Cell Biology; Genetics & Heredity
SC Cell Biology; Genetics & Heredity
GA 255ZY
UT WOS:000327280500151
ER
PT J
AU Moraes, CT
Anderson, V
Mohan, C
AF Moraes, Carlos T.
Anderson, Vernon
Mohan, Charles
TI Translational research in primary mitochondrial diseases: Challenges and
opportunities
SO MITOCHONDRION
LA English
DT Article
DE Workshop; Mitochondrial diseases; Animal models; NIH
AB On March 8-9, 2012, the NIH intramural and extramural research communities as well as representatives from industries and foundations with a common interest in primary mitochondrial diseases met in Bethesda to identify the major barriers to the development of better treatment for mitochondrial diseases. Besides the importance to the patient population, it has become clear in the last decade that advances in understanding and treating primary mitochondrial diseases will impact research into a large number of degenerative conditions known to have a significant mitochondrial dysfunction component in their pathogenic mechanisms (secondary mitochondrial diseases) that affect millions of people, including Alzheimer's disease, Parkinson's disease, diabetes, ALS, autism spectrum disorders, and many others.
We would like to make this discussion available to the scientific community, as it provides a framework on how patient advocacy groups, individual academic units, pharmaceutical companies, and the NIH can interact to address problems related to mitochondrial diseases.
The main goals of this workshop were as follows: (1) to share information related to primary mitochondrial disease among the NIH Intramural and Extramural Research Program Investigators, (2) to develop and/or enhance systems to facilitate future collaboration and sharing of information, (3) to survey obstacles, needs and priorities of primary mitochondrial diseases research, and (4) to develop mechanisms to enhance translation of basic science discoveries to diagnostics and therapeutics.
C1 [Moraes, Carlos T.] Univ Miami, Miller Sch Med, Dept Neurol, Miami, FL 33136 USA.
[Anderson, Vernon] NIGMS, Div Pharmacol Physiol & Biol Chem, Bethesda, MD USA.
[Mohan, Charles] United Mitochondrial Dis Fdn, Pittsburgh, PA USA.
RP Moraes, CT (reprint author), Univ Miami, Miller Sch Med, Dept Neurol, Miami, FL 33136 USA.
EM cmoraes@med.miami.edu
FU UMDF/NIH
FX A UMDF/NIH sponsored workshop to identify barriers to treatments to
mitochondrial diseases.
NR 0
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U1 0
U2 7
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 2013
VL 13
IS 6
BP 945
EP 952
DI 10.1016/j.mito.2013.08.002
PG 8
WC Cell Biology; Genetics & Heredity
SC Cell Biology; Genetics & Heredity
GA 255ZY
UT WOS:000327280500155
PM 23962609
ER
PT J
AU Moody, AD
Batchelor, E
AF Moody, Amie D.
Batchelor, Eric
TI Promoter decoding of transcription factor dynamics
SO MOLECULAR SYSTEMS BIOLOGY
LA English
DT Editorial Material
ID GENE-EXPRESSION; SINGLE-CELL; NOISE; P53
C1 [Moody, Amie D.; Batchelor, Eric] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA.
RP Batchelor, E (reprint author), NCI, Pathol Lab, NIH, Bldg 10,Room B1B42,10 Ctr Dr, Bethesda, MD 20892 USA.
EM batchelore@mail.nih.gov
NR 10
TC 0
Z9 0
U1 0
U2 11
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1744-4292
J9 MOL SYST BIOL
JI Mol. Syst. Biol.
PD NOV
PY 2013
VL 9
AR 703
DI 10.1038/msb.2013.63
PG 2
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 267GK
UT WOS:000328084500001
PM 24189398
ER
PT J
AU Song, C
Chiasson, MA
Nursimulu, N
Hung, SS
Wasmuth, J
Grigg, ME
Parkinson, J
AF Song, Carl
Chiasson, Melissa A.
Nursimulu, Nirvana
Hung, Stacy S.
Wasmuth, James
Grigg, Michael E.
Parkinson, John
TI Metabolic reconstruction identifies strain-specific regulation of
virulence in Toxoplasma gondii
SO MOLECULAR SYSTEMS BIOLOGY
LA English
DT Article
DE flux balance analysis; metabolic reconstruction; strain differences;
Toxoplasma gondii
ID FLUX BALANCE ANALYSIS; PLASMODIUM-FALCIPARUM;
BIOCHEMICAL-CHARACTERIZATION; MYCOBACTERIUM-TUBERCULOSIS;
COPROPORPHYRINOGEN OXIDASE; ESCHERICHIA-COLI; BIOSYNTHESIS; EVOLUTION;
MODELS; HOST
AB Increasingly, metabolic potential is proving to be a critical determinant governing a pathogen's virulence as well as its capacity to expand its host range. To understand the potential contribution of metabolism to strain-specific infectivity differences, we present a constraint-based metabolic model of the opportunistic parasite, Toxoplasma gondii. Dominated by three clonal strains (Type I, II, and III demonstrating distinct virulence profiles), T. gondii exhibits a remarkably broad host range. Integrating functional genomic data, our model (which we term as iCS382) reveals that observed strain-specific differences in growth rates are driven by altered capacities for energy production. We further predict strain-specific differences in drug susceptibilities and validate one of these predictions in a drug-based assay, with a Type I strain demonstrating resistance to inhibitors that are effective against a Type II strain. We propose that these observed differences reflect an evolutionary strategy that allows the parasite to extend its host range, as well as result in a subsequent partitioning into discrete strains that display altered virulence profiles across different hosts, different organs, and even cell types.
C1 [Song, Carl; Nursimulu, Nirvana; Hung, Stacy S.; Wasmuth, James; Parkinson, John] Hosp Sick Children, Program Mol Struct & Funct, Toronto, ON M5G 0A4, Canada.
[Song, Carl; Hung, Stacy S.; Parkinson, John] Univ Toronto, Dept Mol Genet, Toronto, ON, Canada.
[Chiasson, Melissa A.; Grigg, Michael E.] NIAID, NIH, Parasit Dis Lab, Mol Parasitol Sect, Bethesda, MD 20892 USA.
[Nursimulu, Nirvana] Univ Toronto, Dept Comp Sci, Toronto, ON, Canada.
[Parkinson, John] Univ Toronto, Dept Biochem, Toronto, ON, Canada.
RP Parkinson, J (reprint author), Hosp Sick Children, Program Mol Struct & Funct, 21-9709 Peter Gilgan Ctr Res & Learning,686 Bay S, Toronto, ON M5G 0A4, Canada.
EM john.parkinson@utoronto.ca
RI Parkinson, John/A-4424-2008
OI Parkinson, John/0000-0001-9815-1189
FU Canadian Institutes for Health Research (CIHR-MOP) [84556]; Natural
Sciences and Engineering Research Council (NSERC) [188266-04]; Ontario
Ministry of Research and Innovation; Intramural Research Program of the
National Institutes of Health (NIH); National Institute of Allergy and
Infectious Diseases (NIAID)
FX This study was funded by the Canadian Institutes for Health Research
(CIHR-MOP #84556 to JP and MEG) and the Natural Sciences and Engineering
Research Council (NSERC #188266-04 to JP). JP also acknowledges support
from the Ontario Ministry of Research and Innovation. MEG and MAC also
acknowledge support from the Intramural Research Program of the National
Institutes of Health (NIH) and National Institute of Allergy and
Infectious Diseases (NIAID). JP is a member of the Center for the
analysis of genome evolution and function (CAGEF). MEG is a Scholar of
the Canadian Institute for Advanced Research (CIFAR) Program for
Integrated Microbial Biodiversity. Computing resources were provided by
the SciNet HPC Consortium.
NR 81
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U1 0
U2 8
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1744-4292
J9 MOL SYST BIOL
JI Mol. Syst. Biol.
PD NOV
PY 2013
VL 9
AR 708
DI 10.1038/msb.2013.62
PG 17
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 267GK
UT WOS:000328084500006
PM 24247825
ER
PT J
AU Wen, H
Gomella, AA
Patel, A
Lynch, SK
Morgan, NY
Anderson, SA
Bennett, EE
Xiao, XH
Liu, C
Wolfe, DE
AF Wen, Han
Gomella, Andrew A.
Patel, Ajay
Lynch, Susanna K.
Morgan, Nicole Y.
Anderson, Stasia A.
Bennett, Eric E.
Xiao, Xianghui
Liu, Chian
Wolfe, Douglas E.
TI Subnanoradian X-ray phase-contrast imaging using a far-field
interferometer of nanometric phase gratings
SO NATURE COMMUNICATIONS
LA English
DT Article
ID FOURIER-TRANSFORM METHOD; UNWRAPPING ALGORITHM; DIFFRACTION; TOMOGRAPHY;
RETRIEVAL; MICROTOMOGRAPHY; RADIOGRAPHY; MICROSCOPY; RADIATION; RATIO
AB Hard X-ray phase-contrast imaging characterizes the electron density distribution in an object without the need for radiation absorption. The power of phase contrast to resolve subtle changes, such as those in soft tissue structures, lies in its ability to detect minute refractive bending of X-rays. Here we report a far-field, two-arm interferometer based on the new nanometric phase gratings, which can detect X-ray refraction with subnanoradian sensitivity, and at the same time overcomes the fundamental limitation of ultra-narrow bandwidths (Delta lambda/lambda similar to 10(-4)) of the current, most sensitive methods based on crystal interferometers. On a 1.5% bandwidth synchrotron source, we demonstrate clear visualization of blood vessels in unstained mouse organs in simple projection views, with over an order-of-magnitude higher phase contrast than current near-field grating interferometers.
C1 [Wen, Han; Gomella, Andrew A.; Patel, Ajay; Lynch, Susanna K.; Morgan, Nicole Y.; Anderson, Stasia A.; Bennett, Eric E.] NIH, Bethesda, MD 20892 USA.
[Xiao, Xianghui; Liu, Chian] Argonne Natl Lab, Adv Photon Source, Lemont, IL 60439 USA.
[Wolfe, Douglas E.] Penn State Univ, State Coll, PA 16804 USA.
RP Wen, H (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA.
EM han.wen@nih.gov
FU US Department of Energy, Office of Science, Office of Basic Energy
Sciences [DE-AC02-06CH11357]
FX We thank the staff of the NanoFab facility of National Institute of
Standards and Technology, Gaithersburg, Maryland, for their assistance
with fabrication of the gratings; the Animal Surgery and Resources Core
and Dr. Alan Michelson of NHLBI, NIH, for their help with biological
specimens; Dr. Dumitru Mazilu for his help with mechanical design and
fabrication. Use of the Advanced Photon Source at Argonne National
Laboratory was supported by the US Department of Energy, Office of
Science, Office of Basic Energy Sciences, under contract no
DE-AC02-06CH11357.
NR 56
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U1 2
U2 19
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 2041-1723
J9 NAT COMMUN
JI Nat. Commun.
PD NOV
PY 2013
VL 4
AR 2659
DI 10.1038/ncomms3659
PG 9
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 266IU
UT WOS:000328018100001
PM 24189696
ER
PT J
AU Burotto, M
Fojo, AT
AF Burotto, Mauricio
Fojo, Antonio Tito
TI Acetyl-L-Carnitine and Prevention of Chemotherapy-Induced Peripheral
Neuropathy: Can Anything Work?
SO ONCOLOGIST
LA English
DT Editorial Material
C1 [Burotto, Mauricio; Fojo, Antonio Tito] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Fojo, AT (reprint author), NCI, Med Oncol Branch, Ctr Canc Res, NIH, Bldg 10,Room 12N226,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM tfojo@helix.nih.gov
NR 9
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U1 0
U2 0
PU ALPHAMED PRESS
PI DURHAM
PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA
SN 1083-7159
EI 1549-490X
J9 ONCOLOGIST
JI Oncologist
PD NOV
PY 2013
VL 18
IS 11
BP 1151
EP 1152
DI 10.1634/theoncologist.2013-0385
PG 2
WC Oncology
SC Oncology
GA 262ZN
UT WOS:000327776500001
PM 24217999
ER
PT J
AU Gerber, LH
Sikdar, S
Armstrong, K
Diao, GQ
Heimur, J
Kopecky, J
Turo, D
Otto, P
Gebreab, T
Shah, J
AF Gerber, Lynn H.
Sikdar, Siddhartha
Armstrong, Katee
Diao, Guoqing
Heimur, Juliana
Kopecky, John
Turo, Diego
Otto, Paul
Gebreab, Tadesse
Shah, Jay
TI A Systematic Comparison Between Subjects With No Pain and Pain
Associated With Active Myofascial Trigger Points
SO PM&R
LA English
DT Article
ID MUSCLE; NECK; PREVALENCE
AB Objective: To determine whether standard evaluations of pain distinguish subjects with no pain from those with myofascial pain syndromes (MPS) and active myofascial trigger points (MTrPs) and to assess whether self-reports of mood, function, and health-related quality of life differ between these groups.
Design: A prospective, descriptive study.
Setting: University.
Patients: Adults with and without neck pain.
Methods: We evaluated adults with MPS and active (painful) MTrPs and those without pain. Subjects in the "active" (A) group had at least one active MTrP with spontaneous pain that was persistent, lasted longer than 3 months, and had characteristic pain on palpation. Subjects in the "no pain" (NP) group had no spontaneous pain. However, some of these subjects had discomfort upon MTrP palpation (latent MTrP), whereas others in the NP group had no discomfort upon palpation of nodules or had no nodules.
Outcome Measures: Each participant underwent range of motion measurement, a 10-point manual muscle test, and manual and algometric palpation. The latter determined the pain/pressure threshold using an algometer of 4 predetermined anatomic sites along the upper trapezius. Participants rated pain using a verbal analog scale (0-10) and completed the Brief Pain Inventory and Oswestry Disability Scale (which included a sleep subscale), the Short -Form 36 Health Survey, and the Profile of Mood States.
Results: The A group included 24 subjects (mean age 36 years; 16 women), and the NP group included 26 subjects (mean age 26 years; 12 women). Group A subjects differed from NP subjects in the number of latent MTrPs (P = .0062), asymmetrical cervical range of motion (P = .01 for side bending and P = .002 for rotation), and in all pain reports (P < .0001), algometry (P < .03), Profile of Mood States (P < .038), Short Form 36 Health Survey (P < .01), and Oswestry Disability Scale (P < .0001).
Conclusion: A systematic musculoskeletal evaluation of people with MPS reliably distinguishes them from subjects with no pain. The 2 groups are significantly different in their physical findings and self-reports of pain, sleep disturbance, disability, health status, and mood. These findings support the view that a "local" pain syndrome has significant associations with mood, health-related quality of life, and function.
C1 [Gerber, Lynn H.; Armstrong, Katee] George Mason Univ, Coll Hlth & Human Serv, Ctr Study Chron Illness & Disabil, Fairfax, VA 22030 USA.
[Sikdar, Siddhartha; Otto, Paul] George Mason Univ, Volgenau Sch Engn, Dept Elect & Comp Engn, Fairfax, VA 22030 USA.
[Sikdar, Siddhartha; Turo, Diego; Otto, Paul] George Mason Univ, Volgenau Sch Engn, Dept Bioengn, Fairfax, VA 22030 USA.
[Diao, Guoqing] George Mason Univ, Volgenau Sch Engn, Dept Stat, Fairfax, VA 22030 USA.
[Heimur, Juliana; Gebreab, Tadesse; Shah, Jay] NIH, Dept Rehabil Med, Ctr Clin, Bethesda, MD 20892 USA.
[Kopecky, John] George Mason Univ, Coll Sci, Fairfax, VA 22030 USA.
RP Gerber, LH (reprint author), George Mason Univ, Coll Hlth & Human Serv, Ctr Study Chron Illness & Disabil, 4400 Univ Cr, Fairfax, VA 22030 USA.
EM nger-ber1@gmu.edu
OI Sikdar, Siddhartha/0000-0002-6426-2320
FU National Institutes of Health; NIH (NIAMS) [R01AR057348]; NSF; VHA
FX Disclosure related to this publication: grant, National Institutes of
Health; Disclosures related to this publication: grant, NIH (NIAMS grant
R01AR057348 provided funding for this study); support for travel to
meetings for the study or other purposes, AAPM&R, CAPMR, ISURA, GSPN
(travel support for invited talks and/or workshops); Disclosures outside
this publication: grants/grants pending, NIH, NSF, VHA
NR 29
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PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1934-1482
EI 1934-1563
J9 PM&R
JI PM&R
PD NOV
PY 2013
VL 5
IS 11
BP 931
EP 938
DI 10.1016/j.pmrj.2013.06.006
PG 8
WC Rehabilitation; Sport Sciences
SC Rehabilitation; Sport Sciences
GA 260FE
UT WOS:000327579600004
PM 23810811
ER
PT J
AU Ardeljan, D
Chan, CC
AF Ardeljan, Daniel
Chan, Chi-Chao
TI Aging is not a disease: Distinguishing age-related macular degeneration
from aging
SO PROGRESS IN RETINAL AND EYE RESEARCH
LA English
DT Article
DE Age-related macular degeneration; Aging; Homeostasis; Para-inflammation;
Oxidative stress; Retina
ID RETINAL-PIGMENT EPITHELIUM; GLYCATION END-PRODUCTS; COMPLEMENT FACTOR-H;
HUMAN BRUCHS MEMBRANE; ENDOPLASMIC-RETICULUM STRESS; MITOCHONDRIAL-DNA
DAMAGE; HUMAN RPE CELLS; SUBRETINAL DRUSENOID DEPOSITS; KAPPA-B
ACTIVATION; C-REACTIVE PROTEIN
AB Age-related macular degeneration (AMD) is a disease of the outer retina, characterized most significantly by atrophy of photoreceptors and retinal pigment epithelium accompanied with or without choroidal neovascularization. Development of AMD has been recognized as contingent on environmental and genetic risk factors, the strongest being advanced age. In this review, we highlight pathogenic changes that destabilize ocular homeostasis and promote AMD development. With normal aging, photoreceptors are steadily lost, Bruch's membrane thickens, the choroid thins, and hard drusen may form in the periphery. In AMD, many of these changes are exacerbated in addition to the development of disease-specific factors such as soft macular drusen. Para-inflammation, which can be thought of as an intermediate between basal and robust levels of inflammation, develops within the retina in an attempt to maintain ocular homeostasis, reflected by increased expression of the anti-inflammatory cytokine IL-10 coupled with shifts in macrophage plasticity from the pro-inflammatory M1 to the anti-inflammatory M2 polarization. In AMD, imbalances in the M1 and M2 populations together with activation of retinal microglia are observed and potentially contribute to tissue degeneration. Nonetheless, the retina persists in a state of chronic inflammation and increased expression of certain cytokines and inflammasomes is observed. Since not everyone develops AMD, the vital question to ask is how the body establishes a balance between normal age-related changes and the pathological phenotypes in AMD. Published by Elsevier Ltd.
C1 [Ardeljan, Daniel; Chan, Chi-Chao] NEI, Immunopathol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA.
[Ardeljan, Daniel] Johns Hopkins Univ, Sch Med, Baltimore, MD 21205 USA.
RP Chan, CC (reprint author), NEI, NIH, 10 Ctr Dr,10-10N103, Bethesda, MD 20892 USA.
EM dardelj1@jhu.edu; chanc@nei.nih.gov
OI Chan, Chi-Chao/0000-0001-9460-8049
FU NEI
FX The authors state no conflicts of interest. We appreciate Dr. Janet
Sparrow's critical review of the manuscript. This work was supported by
the NEI Intramural Fund.
NR 319
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PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 1350-9462
J9 PROG RETIN EYE RES
JI Prog. Retin. Eye Res.
PD NOV
PY 2013
VL 37
BP 68
EP 89
DI 10.1016/j.preteyeres.2013.07.003
PG 22
WC Ophthalmology
SC Ophthalmology
GA 264VI
UT WOS:000327908700004
PM 23933169
ER
PT J
AU Horowitz, LM
Snyder, DJ
Pao, M
Rosenstein, DL
AF Horowitz, Lisa M.
Snyder, Deborah J.
Pao, Maryland
Rosenstein, Donald L.
TI Response-Suicide Screening in General Hospitals
SO PSYCHOSOMATICS
LA English
DT Letter
C1 [Horowitz, Lisa M.; Snyder, Deborah J.; Pao, Maryland] NIMH, Off Clin Director, NIH, Bethesda, MD 20892 USA.
[Rosenstein, Donald L.] Univ N Carolina, Comprehens Canc Support Program, Chapel Hill, NC USA.
RP Horowitz, LM (reprint author), NIMH, Off Clin Director, NIH, Bethesda, MD 20892 USA.
NR 4
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U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0033-3182
J9 PSYCHOSOMATICS
JI Psychosomatics
PD NOV-DEC
PY 2013
VL 54
IS 6
BP 605
EP 606
PG 3
WC Psychiatry; Psychology
SC Psychiatry; Psychology
GA 258XM
UT WOS:000327492000016
PM 23932536
ER
PT J
AU Bluemke, DA
AF Bluemke, David A.
TI Invited Commentary
SO RADIOGRAPHICS
LA English
DT Editorial Material
C1 NIH, Ctr Clin, Bethesda, MD 20892 USA.
RP Bluemke, DA (reprint author), NIH, Ctr Clin, Bethesda, MD 20892 USA.
NR 1
TC 0
Z9 0
U1 0
U2 1
PU RADIOLOGICAL SOC NORTH AMERICA
PI OAK BROOK
PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA
SN 0271-5333
J9 RADIOGRAPHICS
JI Radiographics
PD NOV-DEC
PY 2013
VL 33
IS 7
AR 7
PG 2
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 262TG
UT WOS:000327759900014
ER
PT J
AU Thomas, RS
Philbert, MA
Auerbach, SS
Wetmore, BA
Devito, MJ
Cote, I
Rowlands, JC
Whelan, MP
Hays, SM
Andersen, ME
Meek, ME
Reiter, LW
Lambert, JC
Clewell, HJ
Stephens, ML
Zhao, QJ
Wesselkamper, SC
Flowers, L
Carney, EW
Pastoor, TP
Petersen, DD
Yauk, CL
Nong, A
AF Thomas, Russell S.
Philbert, Martin A.
Auerbach, Scott S.
Wetmore, Barbara A.
Devito, Michael J.
Cote, Ila
Rowlands, J. Craig
Whelan, Maurice P.
Hays, Sean M.
Andersen, Melvin E.
Meek, M. E. (Bette)
Reiter, Lawrence W.
Lambert, Jason C.
Clewell, Harvey J., III
Stephens, Martin L.
Zhao, Q. Jay
Wesselkamper, Scott C.
Flowers, Lynn
Carney, Edward W.
Pastoor, Timothy P.
Petersen, Dan D.
Yauk, Carole L.
Nong, Andy
TI Incorporating New Technologies Into Toxicity Testing and Risk
Assessment: Moving From 21st Century Vision to a Data-Driven Framework
SO TOXICOLOGICAL SCIENCES
LA English
DT Article
DE in vitro and altenatives; biotransformation and toxicokinetics;
predictive toxicology; risk assessment; safety evaluation; exposure
ID EPAS TOXCAST PROGRAM; ENVIRONMENTAL CHEMICALS; IN-VIVO; TISSUE
DISTRIBUTION; BIOMONITORING DATA; DRUG DISCOVERY; POOLED SAMPLES; IPCS
FRAMEWORK; EXPOSURE; DOSIMETRY
AB Based on existing data and previous work, a series of studies is proposed as a basis toward a pragmatic early step in transforming toxicity testing. These studies were assembled into a data-driven framework that invokes successive tiers of testing with margin of exposure (MOE) as the primary metric. The first tier of the framework integrates data from high-throughput in vitro assays, in vitro-to-in vivo extrapolation (IVIVE) pharmacokinetic modeling, and exposure modeling. The in vitro assays are used to separate chemicals based on their relative selectivity in interacting with biological targets and identify the concentration at which these interactions occur. The IVIVE modeling converts in vitro concentrations into external dose for calculation of the point of departure (POD) and comparisons to human exposure estimates to yield a MOE. The second tier involves short-term in vivo studies, expanded pharmacokinetic evaluations, and refined human exposure estimates. The results from the second tier studies provide more accurate estimates of the POD and the MOE. The third tier contains the traditional animal studies currently used to assess chemical safety. In each tier, the POD for selective chemicals is based primarily on endpoints associated with a proposed mode of action, whereas the POD for nonselective chemicals is based on potential biological perturbation. Based on the MOE, a significant percentage of chemicals evaluated in the first 2 tiers could be eliminated from further testing. The framework provides a risk-based and animal-sparing approach to evaluate chemical safety, drawing broadly from previous experience but incorporating technological advances to increase efficiency.
C1 [Thomas, Russell S.; Wetmore, Barbara A.; Andersen, Melvin E.; Clewell, Harvey J., III] Hamner Inst Hlth Sci, Res Triangle Pk, NC 27709 USA.
[Philbert, Martin A.] Univ Michigan, Sch Publ Hlth, Toxicol Program, Ann Arbor, MI 48019 USA.
[Auerbach, Scott S.; Devito, Michael J.] NIEHS, Div Natl Toxicol Program, NIH, Res Triangle Pk, NC 27709 USA.
[Cote, Ila; Flowers, Lynn] US EPA, Natl Ctr Environm Assessment, Arlington, VA 22202 USA.
[Rowlands, J. Craig; Carney, Edward W.] Dow Chem Co USA, Toxicol & Environm Res & Consulting, Midland, MI 48674 USA.
[Whelan, Maurice P.] European Commiss DG Joint Res Ctr, Inst Hlth & Consumer Protect, Syst Toxicol Unit, Ispra, Italy.
[Hays, Sean M.] Summit Toxicol LLP, Allenspark, CO 80510 USA.
[Meek, M. E. (Bette)] Univ Ottawa, McLaughlin Ctr Populat Hlth Risk Assessment, Ottawa, ON K1N 6N5, Canada.
[Reiter, Lawrence W.] US EPA, Raleigh, NC 27606 USA.
[Lambert, Jason C.; Zhao, Q. Jay; Wesselkamper, Scott C.; Petersen, Dan D.] US EPA, Natl Ctr Environm Assessment, Cincinnati, OH 45268 USA.
[Stephens, Martin L.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA.
[Pastoor, Timothy P.] Syngenta Crop Protect, Toxicol & Hlth Sci Dept, Greensboro, NC 27419 USA.
[Yauk, Carole L.; Nong, Andy] Hlth Canada, Hlth Environm & Consumer Safety Branch, Environm Hlth Sci & Res Bur, Ottawa, ON K1A 0K9, Canada.
RP Thomas, RS (reprint author), Hamner Inst Hlth Sci, 6 Davis Dr,POB 12137, Res Triangle Pk, NC 27709 USA.
EM rthomas@thehamner.org
OI Andersen, Melvin/0000-0002-3894-4811; Thomas,
Russell/0000-0002-2340-0301; Yauk, Carole/0000-0003-4919-876X
FU American Chemistry Council's Long-Range Research Initiative
FX The work by R.S.T., M.E.A., H.J.C. III, and B.A.W. on this manuscript
was supported by the American Chemistry Council's Long-Range Research
Initiative. The views expressed by authors affiliated with the U. S.
Environmental Protection Agency are those of the authors and do not
necessarily reflect the views or policies of the U. S. Environmental
Protection Agency. This article may be the work product of an employee
or group of employees of the National Institute of Environmental Health
Sciences (NIEHS), National Institutes of Health (NIH); however, the
statements, opinions, or conclusions contained therein do not
necessarily represent the statements, opinions, or conclusions of NIEHS,
NIH, or the U. S. government. The authors wish to thank Chad Blystone
and Alex Merrick for reviewing the manuscript.
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PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1096-6080
EI 1096-0929
J9 TOXICOL SCI
JI Toxicol. Sci.
PD NOV
PY 2013
VL 136
IS 1
BP 4
EP 18
DI 10.1093/toxsci/kft178
PG 15
WC Toxicology
SC Toxicology
GA 258KQ
UT WOS:000327458600002
PM 23958734
ER
PT J
AU Gribble, MO
Voruganti, VS
Cropp, CD
Francesconi, KA
Goessler, W
Umans, JG
Silbergeld, EK
Laston, SL
Haack, K
Kao, WHL
Fallin, MD
MacCluer, JW
Cole, SA
Navas-Acien, A
AF Gribble, Matthew O.
Voruganti, Venkata Saroja
Cropp, Cheryl D.
Francesconi, Kevin A.
Goessler, Walter
Umans, Jason G.
Silbergeld, Ellen K.
Laston, Sandra L.
Haack, Karin
Kao, Wen Hong Linda
Fallin, Margaret Daniele
MacCluer, Jean W.
Cole, Shelley A.
Navas-Acien, Ana
TI SLCO1B1 Variants and Urine Arsenic Metabolites in the Strong Heart
Family Study
SO TOXICOLOGICAL SCIENCES
LA English
DT Article
DE American Indians; arsenic metabolism; arsenic species; SLCO1B1; OATPC;
Strong Heart Study
ID METHYLTRANSFERASE AS3MT GENE; DRUG-DRUG INTERACTIONS;
CARDIOVASCULAR-DISEASE; INTESTINAL-ABSORPTION; SOUTHWESTERN TAIWAN;
AMERICAN-INDIANS; LINKAGE ANALYSIS; CANCER RISK; CELL-LINE; EXPOSURE
AB Arsenic species patterns in urine are associated with risk for cancer and cardiovascular diseases. The organic anion transporter coded by the gene SLCO1B1 may transport arsenic species, but its association with arsenic metabolites in human urine has not yet been studied. The objective of this study is to evaluate associations of urine arsenic metabolites with variants in the candidate gene SLCO1B1 in adults from the Strong Heart Family Study. We estimated associations between % arsenic species biomarker traits and 5 single-nucleotide polymorphisms (SNPs) in the SLCO1B1 gene in 157 participants, assuming additive genetics. Linear regression models for each SNP accounted for kinships and were adjusted for sex, body mass index, and study center. The minor allele of rs1564370 was associated with lower %MMA (p .0003) and higher %DMA (p .0002), accounting for 8% of the variance for %MMA and 9% for %DMA. The rs1564370 minor allele homozygote frequency was 17% and the heterozygote frequency was 43%. The minor allele of rs2291075 was associated with lower %MMA (p .0006) and higher %DMA (p .0014), accounting for 7% of the variance for %MMA and 5% for %DMA. The frequency of rs2291075 minor allele homozygotes was 1% and of heterozygotes was 15%. Common variants in SLCO1B1 were associated with differences in arsenic metabolites in a preliminary candidate gene study. Replication of this finding in other populations and analyses with respect to disease outcomes are needed to determine whether this novel candidate gene is important for arsenic-associated disease risks.
C1 [Gribble, Matthew O.; Kao, Wen Hong Linda; Fallin, Margaret Daniele; Navas-Acien, Ana] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA.
[Voruganti, Venkata Saroja; Laston, Sandra L.; Haack, Karin; MacCluer, Jean W.; Cole, Shelley A.] Texas Biomed Res Inst, Dept Genet, San Antonio, TX 78227 USA.
[Cropp, Cheryl D.] NHGRI, Inherited Dis Res Branch, NIH, Baltimore, MD 21224 USA.
[Goessler, Walter] Karl Franzens Univ Graz, Inst Chem Analyt Chem, Graz, Austria.
[Umans, Jason G.] MedStar Hlth Res Inst, Hyattsville, MD 20782 USA.
[Umans, Jason G.] Georgetown Howard Univ Ctr Clin & Translat Sci, Washington, DC 20007 USA.
[Silbergeld, Ellen K.; Navas-Acien, Ana] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Environm Hlth Sci, Baltimore, MD 21205 USA.
[Gribble, Matthew O.; Navas-Acien, Ana] Johns Hopkins Med Inst, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD 21205 USA.
RP Gribble, MO (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, 615 N Wolfe St Off W7513D, Baltimore, MD 21205 USA.
EM mgribble@jhsph.edu
OI Goessler, Walter/0000-0002-0142-9373; Gribble,
Matthew/0000-0002-1614-2981
FU National Heart Lung and Blood Institute [R01HL090863]; National Heart
Lung and Blood Institute (SHS) [HL41642, HL41652, HL41654, HL065520,
HL65521]; National Institute of Environmental Health Sciences
[R01ES021367, P30ES03819]; National Institute of Diabetes and Digestive
and Kidney Diseases [5T32DK062707-10]; National Center for Research
Resources [C06 RR13556, C06 RR017515]
FX National Heart Lung and Blood Institute (R01HL090863, SHS grants
HL41642, HL41652, HL41654, HL065520, HL65521); National Institute of
Environmental Health Sciences (R01ES021367, P30ES03819); National
Institute of Diabetes and Digestive and Kidney Diseases
(5T32DK062707-10); National Center for Research Resources (C06 RR13556,
C06 RR017515).
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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 2013
VL 136
IS 1
BP 19
EP 25
DI 10.1093/toxsci/kft181
PG 7
WC Toxicology
SC Toxicology
GA 258KQ
UT WOS:000327458600003
PM 23970802
ER
PT J
AU Nussinov, R
Tsai, CJ
Mattos, C
AF Nussinov, Ruth
Tsai, Chung-Jung
Mattos, Carla
TI 'Pathway drug cocktail': targeting Ras signaling based on structural
pathways
SO TRENDS IN MOLECULAR MEDICINE
LA English
DT Review
DE cancer; drug discovery; parallel pathways; classification; structures;
oncogenic mutations
ID ACQUIRED-RESISTANCE; MEK INHIBITORS; PROTEOME SCALE; MAPK-PATHWAY;
CANCER-CELLS; H-RAS; PROTEINS; SWITCH; BRAF; BINDING
AB Tumors bearing Ras mutations are notoriously difficult to treat. Drug combinations targeting the Ras protein or its pathway have also not met with success. 'Pathway drug cocktails', which are combinations aiming at parallel pathways, appear more promising; however, to be usefully exploited, a repertoire of classified pathway combinations is desirable. This challenge would be facilitated by the availability of the structural network of signaling pathways. When integrated with functional and systems level clinical data, they can be powerful in advancing novel therapeutic platforms. Based on structural knowledge, drug cocktails may tear into multiple cellular processes that drive tumorigenesis, and help in deciphering the interrelationship between Ras mutations and the rewired Ras network. The pathway drug cocktail paradigm can be applied to other signaling protein targets.
C1 [Nussinov, Ruth; Tsai, Chung-Jung] NCI, Basic Res Program, SAIC Frederick Inc, Canc & Inflammat Program,Ctr Canc Res, Ft Detrick, MD 21702 USA.
[Nussinov, Ruth] Tel Aviv Univ, Sackler Sch Med, Dept Human Genet, Sackler Inst Mol Med, IL-69978 Tel Aviv, Israel.
[Mattos, Carla] Northeastern Univ, Dept Chem & Chem Biol, Boston, MA 02115 USA.
RP Nussinov, R (reprint author), NCI, Basic Res Program, SAIC Frederick Inc, Canc & Inflammat Program,Ctr Canc Res, Ft Detrick, MD 21702 USA.
EM NussinoR@helix.nih.gov
FU National Cancer Institute, National Institutes of Health (NIH)
[HHSN261200800001E]; Intramural Research Program of the NIH, National
Cancer Institute, Center for Cancer Research; extramural program [R56
CA096867]
FX We would like to thank Christian W. Johnson for making Figures 3 and 4.
This project has been funded in whole or in part with Federal funds from
the National Cancer Institute, National Institutes of Health (NIH),
under contract number HHSN261200800001E. This research was supported (in
part) by the Intramural Research Program of the NIH, National Cancer
Institute, Center for Cancer Research (R.N.) and by the extramural
program under grant number R56 CA096867 (C.M.).
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PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1471-4914
EI 1471-499X
J9 TRENDS MOL MED
JI Trends Mol. Med
PD NOV
PY 2013
VL 19
IS 11
BP 695
EP 704
DI 10.1016/j.molmed.2013.07.009
PG 10
WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research &
Experimental
SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental
Medicine
GA 265BA
UT WOS:000327923500006
PM 23953481
ER
PT J
AU Molina-Cruz, A
Lehmann, T
Knockel, J
AF Molina-Cruz, Alvaro
Lehmann, Tovi
Knoeckel, Julia
TI Could culicine mosquitoes transmit human malaria?
SO TRENDS IN PARASITOLOGY
LA English
DT Review
DE malaria; transmission; mosquito; Culex; Anopheles
ID COMPLEMENT-LIKE PROTEIN; SUB-SAHARAN AFRICA; ANOPHELES-GAMBIAE;
CHIKUNGUNYA VIRUS; PLASMODIUM-FALCIPARUM; LOCAL ADAPTATION; XANTHURENIC
ACID; AEDES-AEGYPTI; ONYONG-NYONG; WEST-NILE
AB Human malaria is known to be transmitted strictly by anopheline mosquitoes. Culicine mosquitoes such as Aedes spp. and Culex spp. are important vectors of other human pathogens including viruses and filarial worms, but have never been observed to transmit mammalian malarias. Culicines do transmit avian malarias and, interestingly, allow partial development of mammalian-infectious Plasmodium parasites, implying that physiological barriers in the mosquitoes prevent parasite transmission. Although the mechanism(s) are not known, the mosquito immune system is probably involved in eliminating Plasmodium. However, Plasmodium has shown substantial capacity to adapt to new vectors, and current ecological changes caused by humans could promote adaptation of human-infectious Plasmodium parasites to culicines. Such an event could have widespread epidemiological implications and therefore merits attention.
C1 [Molina-Cruz, Alvaro; Lehmann, Tovi; Knoeckel, Julia] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD USA.
RP Knockel, J (reprint author), NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD USA.
EM julia.knoeckel@gmail.com
OI Knoeckel, Julia/0000-0001-6688-7714
FU National Institutes of Health Intramural Research Program
FX We would like to thank Louis H. Miller and Jose Ribeiro (Laboratory for
Malaria and Vector Research, National Institute of Allergy and
Infectious Diseases, National Institutes of Health), Scott Weaver
(University of Texas Medical Branch, Galveston, TX), Peter Armbruster
(Georgetown University, Washington DC), and Louis Lambrechts (Institut
Pasteur, Paris, France) for helpful suggestions and insightful comments
on the manuscript, and Jose Luis Ramirez for assistance in image
processing. This work was supported by the National Institutes of Health
Intramural Research Program.
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PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1471-4922
EI 1471-5007
J9 TRENDS PARASITOL
JI Trends Parasitol.
PD NOV
PY 2013
VL 29
IS 11
BP 530
EP 537
DI 10.1016/j.pt.2013.09.003
PG 8
WC Parasitology
SC Parasitology
GA 261UN
UT WOS:000327690200004
PM 24140295
ER
PT J
AU Gunduz-Cinar, O
Hill, MN
McEwen, BS
Holmes, A
AF Gunduz-Cinar, Ozge
Hill, Matthew N.
McEwen, Bruce S.
Holmes, Andrew
TI Amygdala FAAH and anandamide: mediating protection and recovery from
stress
SO TRENDS IN PHARMACOLOGICAL SCIENCES
LA English
DT Review
DE endocannabinoid; post-traumatic stress disorder; anxiety; fear;
depression; 2-AG
ID ACID AMIDE HYDROLASE; CB1 CANNABINOID RECEPTORS; RAT BASOLATERAL
AMYGDALA; CONTEXTUAL FEAR MEMORY; ENDOCANNABINOID SYSTEM; CONDITIONED
FEAR; MONOACYLGLYCEROL LIPASE; PREFRONTAL CORTEX; NERVOUS-SYSTEM;
FUNCTIONAL INTERACTIONS
AB A long-standing literature linking endocannabinoids (ECBs) to stress, fear, and anxiety has led to growing interest in developing novel anxiolytics targeting the ECB system. Following rapid on-demand biosynthesis and degradation upon neuronal activation, the ECB N-arachidonoylethanolamide (anandamide, AEA) is actively degraded by the serine hydrolase enzyme, fatty acid amide hydrolase (FAAH). Exposure to stress rapidly mobilizes FAAH to deplete the signaling pool of AEA and increase neuronal excitability in a key anxiety-mediating region the basolateral amygdala (BLA). Gene deletion or pharmacological inhibition of FAAH prevents stress-induced reductions in AEA and associated increases in BLA dendritic hypertrophy and anxiety-like behavior. Additionally, inhibition of FAAH facilitates long-term fear extinction and rescues deficient fear extinction in rodent models by enhancing AEA CBI (cannabinoid type 1) receptor signaling and synaptic plasticity in the BLA. These preclinical findings propose restoring deficient BLA AEA levels by pharmacologically inhibiting FAAH as a mechanism to therapeutically mitigate the effects of traumatic stress.
C1 [Gunduz-Cinar, Ozge; Holmes, Andrew] NIAAA, Lab Behav & Genom Neurosci, NIH, Bethesda, MD 20892 USA.
[Hill, Matthew N.] Univ Calgary, Hotchkiss Brain Inst, Dept Cell Biol, Calgary, AB, Canada.
[Hill, Matthew N.] Univ Calgary, Hotchkiss Brain Inst, Dept Psychiat & Anat, Calgary, AB, Canada.
[McEwen, Bruce S.] Rockefeller Univ, Neuroendocrinol Lab, New York, NY 10021 USA.
RP Gunduz-Cinar, O (reprint author), NIAAA, Lab Behav & Genom Neurosci, NIH, Bethesda, MD 20892 USA.
EM ozge.gunduzcinar@nih.gov; mnhill@ucalgary.ca
FU NIAAA Intramural Research Program; Department of Defense in the Center
for Neuroscience and Regenerative Medicine; Canadian Institutes of
Health Research; Tier II Canada Research Chair
FX O.G-C. and A.H. are supported by the NIAAA Intramural Research Program
and Department of Defense in the Center for Neuroscience and
Regenerative Medicine. M.N.H. is the recipient of a Tier II Canada
Research Chair and operating funds from the Canadian Institutes of
Health Research.
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PI LONDON
PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND
SN 0165-6147
J9 TRENDS PHARMACOL SCI
JI Trends Pharmacol. Sci.
PD NOV
PY 2013
VL 34
IS 11
BP 637
EP 644
DI 10.1016/j.tips.2013.08.008
PG 8
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 260FS
UT WOS:000327581000009
PM 24325918
ER
PT J
AU Bosserman, MA
Downey, T
Noinaj, N
Buchanan, SK
Rohr, J
AF Bosserman, Mary A.
Downey, Theresa
Noinaj, Nicholas
Buchanan, Susan K.
Rohr, Juergen
TI Molecular Insight into Substrate Recognition and Catalysis of
Baeyer-Villiger Monooxygenase MtmOIV, the Key Frame-Modifying Enzyme in
the Biosynthesis of Anticancer Agent Mithramycin
SO ACS CHEMICAL BIOLOGY
LA English
DT Article
ID ANTITUMOR ANTIBIOTIC MITHRAMYCIN; X-RAY-DIFFRACTION; PRODUCER
STREPTOMYCES-ARGILLACEUS; COMBINATORIAL BIOSYNTHESIS;
PSEUDOMONAS-PUTIDA; CRYSTAL-STRUCTURE; DIKETOCAMPHANE MONOOXYGENASE;
ENANTIOSELECTIVE OXIDATIONS; PAGETS-DISEASE; CANCER-CELLS
AB Baeyer-Villiger monooxygenases (BVMOs) have been shown to play key roles for the biosynthesis of important natural products. MtmOIV, a homodimeric FAD- and NADPH-dependent BVMO, catalyzes the key frame-modifying steps of the mithramycin biosynthetic pathway, including an oxidative C-C bond cleavage, by converting its natural substrate premithramycin B into mithramycin DK, the immediate precursor of mithramycin. The drastically improved protein structure of MtmOIV along with the high-resolution structure of MtmOIV in complex with its natural substrate premithramycin B are reported here, revealing previously undetected key residues that are important for substrate recognition and catalysis. Kinetic analyses of selected mutants allowed us to probe the substrate binding pocket of MtmOIV and also to discover the putative NADPH binding site. This is the first substrate-bound structure of MtmOIV providing new insights into substrate recognition and catalysis, which paves the way for the future design of a tailored enzyme for the chemo-enzymatic preparation of novel mithramycin analogues.
C1 [Bosserman, Mary A.; Downey, Theresa; Rohr, Juergen] Univ Kentucky, Coll Pharm, Dept Pharmaceut Sci, Lexington, KY 40536 USA.
[Bosserman, Mary A.; Noinaj, Nicholas; Buchanan, Susan K.] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Rohr, J (reprint author), Univ Kentucky, Coll Pharm, Dept Pharmaceut Sci, 789 South Limestone St, Lexington, KY 40536 USA.
EM jrohr2@email.uky.edu
RI Rohr, Jurgen/G-5375-2014
OI Rohr, Jurgen/0000-0001-6447-5951
FU NIH [CA 091901]; NIH, National Institute of Diabetes and Digestive and
Kidney Diseases; U.S. Department of Energy
FX This work was supported by NIH grant CA 091901 to J.R. 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. Data were
collected at Southeast Regional Collaborative Access Team (SER-CAT)
beamline 22-ID at the Advanced Photon Source, Argonne National
Laboratory. Use of the Advanced Photon Source was supported by the U.S.
Department of Energy. We also wish to acknowledge S. G. Van Lanen and J.
S. Thorson for sharing lab instrumentation with us.
NR 60
TC 8
Z9 8
U1 3
U2 21
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1554-8929
EI 1554-8937
J9 ACS CHEM BIOL
JI ACS Chem. Biol.
PD NOV
PY 2013
VL 8
IS 11
BP 2466
EP 2477
DI 10.1021/cb400399b
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 254OP
UT WOS:000327175300015
PM 23992662
ER
PT J
AU Bertola, A
Park, O
Gao, B
AF Bertola, A.
Park, O.
Gao, B.
TI Chronic plus binge ethanol feeding synergistically induces neutrophil
infiltration and liver injury: A critical role for E-selectin
SO ALCOHOL
LA English
DT Meeting Abstract
CT Alcohol-and-Immunology-Research-Interest-Group (AIRIG) Meeting on
Alcohol and Inflammatory Responses
CY NOV 22, 2013
CL Loyola Univ Chicago, Hlth Sci Campus, Dept Surg, Maywood, IL
SP Alcohol & Immunol Res Interest Grp
HO Loyola Univ Chicago, Hlth Sci Campus, Dept Surg
C1 [Bertola, A.; Park, O.; Gao, B.] NIAAA, Lab Liver Dis, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0741-8329
EI 1873-6823
J9 ALCOHOL
JI Alcohol
PD NOV
PY 2013
VL 47
IS 7
MA 3
BP 568
EP 568
PG 1
WC Substance Abuse; Pharmacology & Pharmacy; Toxicology
SC Substance Abuse; Pharmacology & Pharmacy; Toxicology
GA 260FX
UT WOS:000327581500012
ER
PT J
AU Mathews, SA
Feng, D
Gao, B
AF Mathews, S. A.
Feng, D.
Gao, B.
TI Natural killer T cells play an important role in chronic plus binge
ethanol-induced liver injury
SO ALCOHOL
LA English
DT Meeting Abstract
CT Alcohol-and-Immunology-Research-Interest-Group (AIRIG) Meeting on
Alcohol and Inflammatory Responses
CY NOV 22, 2013
CL Loyola Univ Chicago, Hlth Sci Campus, Dept Surg, Maywood, IL
SP Alcohol & Immunol Res Interest Grp
HO Loyola Univ Chicago, Hlth Sci Campus, Dept Surg
C1 [Mathews, S. A.; Feng, D.; Gao, B.] NIAAA, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0741-8329
EI 1873-6823
J9 ALCOHOL
JI Alcohol
PD NOV
PY 2013
VL 47
IS 7
BP 572
EP 572
PG 1
WC Substance Abuse; Pharmacology & Pharmacy; Toxicology
SC Substance Abuse; Pharmacology & Pharmacy; Toxicology
GA 260FX
UT WOS:000327581500028
ER
PT J
AU Scoffone, HM
Krajewski, M
Zorca, S
Bereal-Williams, C
Littel, P
Seamon, C
Mendelsohn, L
Footman, E
Abi-Jaoudeh, N
Sachdev, V
Machado, RF
Cuttica, M
Shamburek, R
Cannon, RO
Remaley, A
Minniti, CP
Kato, GJ
AF Scoffone, Heather M.
Krajewski, Megan
Zorca, Suzana
Bereal-Williams, Candice
Littel, Patricia
Seamon, Catherine
Mendelsohn, Laurel
Footman, Eleni
Abi-Jaoudeh, Nadine
Sachdev, Vandana
Machado, Roberto F.
Cuttica, Michael
Shamburek, Robert
Cannon, Richard O., III
Remaley, Alan
Minniti, Caterina P.
Kato, Gregory J.
TI Effect of Extended-Release Niacin on Serum Lipids and on Endothelial
Function in Adults With Sickle Cell Anemia and Low High-Density
Lipoprotein Cholesterol Levels
SO AMERICAN JOURNAL OF CARDIOLOGY
LA English
DT Article
ID VASCULAR REACTIVITY; METABOLIC SYNDROME; DISEASE; DYSFUNCTION;
ATHEROSCLEROSIS; HYPERTENSION; MECHANISM; MARKERS
AB Through bound apolipoprotein A-I (apoA-I), high-density lipoprotein cholesterol (HDL-C) activates endothelial nitric oxide synthase, inducing vasodilation. Because patients with sickle cell disease (SCD) have low apoA-I and endothelial dysfunction, we conducted a randomized, double-blinded, placebo-controlled trial to test whether extended-release niacin (niacin-ER) increases apoA-I-containing HDL-C and improves vascular function in SCD. Twenty-seven patients with SCD with levels of HDL-C <39 mg/dl or apoA-I <99 mg/dl were randomized to 12 weeks of niacin-ER, increased in 500-mg increments to a maximum of 1,500 mg/day, or placebo. The primary outcome was the absolute change in HDL-C level after 12 weeks, with endothelial function assessed before and at the end of treatment. Niacin-ER-treated patients trended to greater increase in HDL-C level compared with placebo treatment at 12 weeks (5.1 +/- 7.7 vs 0.9 +/- 3.8 mg/dl, 1-tailed p = 0.07), associated with significantly greater improvements in the ratios of low-density lipoprotein to HDL-C levels (1.24 vs 1.95, p = 0.003) and apolipoprotein B to apoA-I levels (0.46 vs 0.58, p = 0.03) compared with placebo-treated patients. No improvements were detected in 3 independent vascular physiology assays of endothelial function. Thus, the relatively small changes in HDL-C levels achieved by the dose of niacin-ER used in our study are not associated with improved vascular function in patients with SCD with initially low levels of apoA-I or HDL-C. Published by Elsevier Inc.
C1 [Scoffone, Heather M.] Case Western Reserve Univ, Cleveland Clin, Lerner Coll Med, Bethesda, MD USA.
[Scoffone, Heather M.; Krajewski, Megan; Zorca, Suzana; Bereal-Williams, Candice; Littel, Patricia; Seamon, Catherine; Mendelsohn, Laurel; Footman, Eleni; Machado, Roberto F.; Minniti, Caterina P.; Kato, Gregory J.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
[Sachdev, Vandana; Shamburek, Robert; Cannon, Richard O., III; Remaley, Alan] NHLBI, Cardiovasc & Pulm Branch, NIH, Bethesda, MD 20892 USA.
[Abi-Jaoudeh, Nadine] NIH, Dept Radiol, Ctr Clin, Bethesda, MD 20892 USA.
[Machado, Roberto F.; Cuttica, Michael] NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA.
RP Kato, GJ (reprint author), NHLBI, Hematol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM katogj@upmc.edu
RI Kato, Gregory/I-7615-2014
OI Kato, Gregory/0000-0003-4465-3217
FU NIH Clinical Research Training Program; Case Western Reserve University
Clinical Research Scholars Program
FX The authors are grateful to the patients with sickle cell disease who
enrolled on this study. They also thank additional clinical research
staff who assisted in the recruitment and follow-up of these patients,
including James Nichols, RN. The authors thank Mary K. Hall, CIP, and
Stephanie Housel, MS, for protocol management. Dr. Scoffone acknowledges
the support of the NIH Clinical Research Training Program and the Case
Western Reserve University Clinical Research Scholars Program.
NR 26
TC 4
Z9 4
U1 0
U2 1
PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC
PI BRIDGEWATER
PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA
SN 0002-9149
EI 1879-1913
J9 AM J CARDIOL
JI Am. J. Cardiol.
PD NOV 1
PY 2013
VL 112
IS 9
BP 1499
EP 1504
DI 10.1016/j.amjcard.2013.06.035
PG 6
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 253QJ
UT WOS:000327104100039
PM 24035168
ER
PT J
AU Klein, R
Li, XH
Kuo, JZ
Klein, BEK
Cotch, MF
Wong, TY
Taylor, KD
Rotter, JI
AF Klein, Ronald
Li, Xiaohui
Kuo, Jane Z.
Klein, Barbara E. K.
Cotch, Mary Frances
Wong, Tien Y.
Taylor, Kent D.
Rotter, Jerome I.
TI Associations of Candidate Genes to Age-Related Macular Degeneration
Among Racial/Ethnic Groups in the Multi-Ethnic Study of Atherosclerosis
SO AMERICAN JOURNAL OF OPHTHALMOLOGY
LA English
DT Article
ID COMPLEMENT-FACTOR-H; CARDIOVASCULAR-DISEASE; CHINESE POPULATION;
RACIAL-DIFFERENCES; UNITED-STATES; PREVALENCE; MACULOPATHY;
POLYMORPHISMS; EYE; LOC387715
AB PURPOSE: To describe the relationships of selected candidate genes to the prevalence of early age-related macular degeneration (AMD) in a cohort of whites, blacks, Hispanics, and Chinese Americans.
DESIGN: Cross-sectional study.
METHODS: SETTING: Multicenter study. STUDY POPULATION: A total of 2456 persons aged 45-84 years with genotype information and fundus photographs. PROCEDURES: Twelve of 2862 single nucleotide polymorphisms (SNPs) from 11 of 233 candidate genes for cardiovascular disease were selected for analysis based on screening with marginal unadjusted P value <.001 within 1 or more racial/ethnic groups. Logistic regression models tested for association in case-control samples. MAIN OUTCOME MEASURE: Prevalence of early AlVID.
RESULTS: Early AMD was present in 4.0% of the cohort and varied from 2.4% in blacks to 6.0% in whites. The odds ratio increased from 2.3 for 1 to 10.0 for 4 risk alleles in a joint effect analysis of Age-Related Maculopathy Susceptibility 2 rs10490924 and Complement Factor H Y402H (P for trend = 4.2x 10(-7)). Frequencies of each SNP varied among the racial/ethnic groups. Adjusting for age and other factors, few statistically significant associations of the 12 SNPs with AMD were consistent "across all groups. In a multivariate model, most candidate genes did not attenuate the comparatively higher odds of AMD in whites. The higher frequency of risk alleles for several SNPs in Chinese Americans may partially explain their AMD frequency's approaching that of whites.
CONCLUSIONS: The relationships of 11 candidate genes to early AMD varied among 4 racial/ethnic groups, and partially explained the observed variations in early AMD prevalence among them. ((C) 2013 by Elsevier Inc. All rights reserved.)
C1 [Klein, Ronald; Klein, Barbara E. K.] Univ Wisconsin, Dept Ophthalmol & Visual Sci, Sch Med & Publ Hlth, Madison, WI 53726 USA.
[Li, Xiaohui; Kuo, Jane Z.; Taylor, Kent D.; Rotter, Jerome I.] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA.
[Cotch, Mary Frances] NEI, Div Epidemiol & Clin Applicat, NIH, Bethesda, MD 20892 USA.
[Wong, Tien Y.] Natl Univ Singapore, Singapore Eye Res Inst, Singapore 117548, Singapore.
[Wong, Tien Y.] Univ Melbourne, Ctr Eye Res Australia, Melbourne, Vic 3010, Australia.
RP Klein, R (reprint author), Univ Wisconsin, Dept Ophthalmol & Visual Sci, 610 N Walnut St,4th Floor WARF, Madison, WI 53726 USA.
EM kleinr@epi.ophth.wisc.edu
OI Cotch, Mary Frances/0000-0002-2046-4350; Klein,
Ronald/0000-0002-4428-6237
FU National Heart, Lung, and Blood Institute [N01-HC-95159, N01-HC-95165,
N01-HC-95169]; MESA [R01-HL071051, R01-HL071205, R01-HL071250,
R01-HL071251, R01-HL071252, R01-HL071258, R01-HL071259]; NIH Intramural
Research Award [ZIAEY000403]; NIH [HL69979]
FX The authors have no proprietary or commercial interest in any materials
discussed in this article. The Multi-Ethnic Study of Atherosclerosis
(MESA) was supported by contracts N01-HC-95159 through N01-HC-95165 and
N01-HC-95169 from the National Heart, Lung, and Blood Institute, MESA
Family was conducted and supported in collaboration with MESA
investigators by grants and contracts R01-HL071051, R01-HL071205,
R01-HL071250, R01-HL071251, R01-HL071252, R01-HL071258, R01-HL071259,
and NIH Intramural Research Award ZIAEY000403. Additional support was
provided by NIH grant HL69979 (R.K. and.T.Y.W.) and in part by the
Cedars-Sinai Board of Governors' Chair in Medical Genetics (J.I.R.).
None of the above named sponsors or funding organizations had any role
in the design or conduct of this research. The content is solely the
responsibility of the authors and does not necessarily reflect the
official views of the National Heart, Lung, and Blood Institute; the
National Eye Institute; or the National Institutes of Health.
Contributions of authors: design of the study (R.K.); conduct of the
study (R.K.); collection of data (R.K., M.F.C., PR.); analysis of data
(X.L., J.Z.K., K.D.T.); interpretation of the data (J.I.R., X.L.,
J.Z.K., B.E.K.K., R.K.); manuscript preparation (R.K., B.E.K.K.,
J:I.R.); manuscript review (XL., J.Z.K., B.E.K.K., M.F.C., T.Y.W.,
K.D.T., J.I.R.); and manuscript approval (XL., J.Z.K., B.E.K.K., M.F.C.,
T.Y.W., K.D.T., J.I.R.).
NR 49
TC 8
Z9 8
U1 0
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9394
EI 1879-1891
J9 AM J OPHTHALMOL
JI Am. J. Ophthalmol.
PD NOV
PY 2013
VL 156
IS 5
BP 1010
EP 1020
DI 10.1016/j.ajo.2013.06.004
PG 11
WC Ophthalmology
SC Ophthalmology
GA 250NJ
UT WOS:000326859200021
PM 23938121
ER
PT J
AU Jin, SM
Youle, RJ
AF Jin, Seok Min
Youle, Richard J.
TI The accumulation of misfolded proteins in the mitochondrial matrix is
sensed by PINK1 to induce PARK2/Parkin-mediated mitophagy of polarized
mitochondria
SO AUTOPHAGY
LA English
DT Article
DE unfolded protein response; mitochondria; PINK1; PARK2; Parkin;
mitophagy; LONP
ID MAMMALIAN-CELLS; PARKIN; IMPORT; ACTIVATION; MUTATIONS; PROTEASE;
TRANSLOCATION; REQUIREMENT; RECRUITMENT; CHAPERONES
AB Defective mitochondria exert deleterious effects on host cells. To manage this risk, mitochondria display several lines of quality control mechanisms: mitochondria-specific chaperones and proteases protect against misfolded proteins at the molecular level, and fission/fusion and mitophagy segregate and eliminate damage at the organelle level. An increase in unfolded proteins in mitochondria activates a mitochondrial unfolded protein response (UPRmt) to increase chaperone production, while the mitochondrial kinase PINK1 and the E3 ubiquitin ligase PARK2/Parkin, whose mutations cause familial Parkinson disease, remove depolarized mitochondria through mitophagy. It is unclear, however, if there is a connection between those different levels of quality control (QC). Here, we show that the expression of unfolded proteins in the matrix causes the accumulation of PINK1 on energetically healthy mitochondria, resulting in mitochondrial translocation of PARK2, mitophagy and subsequent reduction of unfolded protein load. Also, PINK1 accumulation is greatly enhanced by the knockdown of the LONP1 protease. We suggest that the accumulation of unfolded proteins in mitochondria is a physiological trigger of mitophagy.
C1 [Jin, Seok Min; Youle, Richard J.] NINDS, Biochem Sect, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA.
RP Youle, RJ (reprint author), NINDS, Biochem Sect, Surg Neurol Branch, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
EM youler@ninds.nih.gov
FU National Institute of Neurological Disorders and Stroke
FX We thank Dr Nick J Hoogenraad for kindly providing the OTC constructs.
This work is supported by the National Institute of Neurological
Disorders and Stroke intramural program.
NR 32
TC 80
Z9 83
U1 0
U2 13
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 1554-8627
EI 1554-8635
J9 AUTOPHAGY
JI Autophagy
PD NOV 1
PY 2013
VL 9
IS 11
BP 1750
EP 1757
DI 10.4161/auto.26122
PG 8
WC Cell Biology
SC Cell Biology
GA 257XM
UT WOS:000327421100011
PM 24149988
ER
PT J
AU Yamano, K
Youle, RJ
AF Yamano, Koji
Youle, Richard J.
TI PINK1 is degraded through the N-end rule pathway
SO AUTOPHAGY
LA English
DT Article
DE mitochondrial import; PARKIN; ubiquitin; PARL; mitophagy
ID UBIQUITIN LIGASE; MITOCHONDRIAL-MEMBRANE; PARKINSONS-DISEASE; PROTEASE
PARL; IMPORT; LOCALIZATION; CLEAVAGE; MUTANTS; KINASE; DROSOPHILA-PINK1
AB PINK1, a mitochondrial serine/threonine kinase, is the product of a gene mutated in an autosomal recessive form of Parkinson disease. PINK1 is constitutively degraded by an unknown mechanism and stabilized selectively on damaged mitochondria where it can recruit the E3 ligase PARK2/PARKIN to induce mitophagy. Here, we show that, under steady-state conditions, endogenous PINK1 is constitutively and rapidly degraded by E3 ubiquitin ligases UBR1, UBR2 and UBR4 through the N-end rule pathway. Following precursor import into mitochondria, PINK1 is cleaved in the transmembrane segment by a mitochondrial intramembrane protease PARL generating an N-terminal destabilizing amino acid and then retrotranslocates from mitochondria to the cytosol for N-end recognition and proteasomal degradation. Thus, sequential actions of mitochondrial import, PARL-processing, retrotranslocation and recognition by N-end rule E3 enzymes for the ubiquitin proteosomal degradation defines the rapid PINK1 turnover. PINK1 steady-state elimination by the N-end rule identifies a novel organelle to cytoplasm turnover pathway that yields a mechanism to flag damaged mitochondria for autophagic elimination.
C1 [Yamano, Koji; Youle, Richard J.] NINDS, Biochem Sect, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA.
RP Youle, RJ (reprint author), NINDS, Biochem Sect, Surg Neurol Branch, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA.
EM youler@ninds.nih.gov
FU Japan Society for the Promotion of Science; National Institute of
Neurological Disorders and Stroke
FX We thank C Wang for construction of the pink1 KO HeLa cell line, DP
Sideris and the other members of the Youle laboratory for valuable
discussions and comments, Y Li for help with mass spectrometry, YT Kwon
for the kind gift of
ubr1-/-ubr2-/-LucRNAi and
ubr1-/-ubr2-/-Ubr4RNAi MEF cells and of
anti-UBR1 and anti-UBR2 antibodies, B De Strooper for parl-/-
MEFs and Z Zang for pink1-/- MEFs. This research is supported
by Japan Society for the Promotion of Science Postdoctoral Fellowships
for Research Abroad (to KY) and by the National Institute of
Neurological Disorders and Stroke intramural program.
NR 39
TC 101
Z9 104
U1 0
U2 15
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 1554-8627
EI 1554-8635
J9 AUTOPHAGY
JI Autophagy
PD NOV 1
PY 2013
VL 9
IS 11
BP 1758
EP 1769
DI 10.4161/auto.24633
PG 12
WC Cell Biology
SC Cell Biology
GA 257XM
UT WOS:000327421100012
PM 24121706
ER
PT J
AU Lu, Y
You, M
Ghazoui, Z
Liu, PY
Vedell, PT
Wen, WD
Bode, AM
Grubbs, CJ
Lubet, RA
AF Lu, Yan
You, Ming
Ghazoui, Zara
Liu, Pengyuan
Vedell, Peter T.
Wen, Weidong
Bode, Ann M.
Grubbs, Clinton J.
Lubet, Ronald A.
TI Concordant Effects of Aromatase Inhibitors on Gene Expression in ER+ Rat
and Human Mammary Cancers and Modulation of the Proteins Coded by These
Genes
SO CANCER PREVENTION RESEARCH
LA English
DT Article
ID HUMAN BREAST-CANCER; SPRAGUE-DAWLEY RATS; POSTMENOPAUSAL WOMEN;
CELL-PROLIFERATION; VOROZOLE; TAMOXIFEN; LETROZOLE; THERAPY; TUMORS;
MODEL
AB Aromatase inhibitors are effective in therapy/prevention of estrogen receptor-positive (ER+) breast cancers. Rats bearing methylnitrosourea (MNU)-induced ER+ mammary cancers were treated with the aromatase inhibitor vorozole (1.25 mg/kg BW/day) for five days. RNA expression showed 162 down-regulated and 180 upregulated (P < 0.05 and fold change >1.5) genes. Genes modulated by vorozole were compared with published data from four clinical neoadjuvant trials using aromatase inhibitors (anastrozole or letrozole). More than 30 genes and multiple pathways exhibited synchronous changes in animal and human datasets. Cell-cycle genes related to chromosome condensation in prometaphase [anaphase-prometaphase complex (APC) pathway, including Aurora-A kinase, BUBR1B, TOP2, cyclin A, cyclin B CDC2, and TPX-2)] were downregulated in animal and human studies reflecting the strong antiproliferative effects of aromatase inhibitors. Comparisons of rat arrays with a cell culture study where estrogen was removed from MCF-7 cells showed decreased expression of E2F1-modulated genes as a major altered pathway. Alterations of the cell cycle and E2F-related genes were confirmed in a large independent set of human samples (81 pairs baseline and two weeks anastrozole treatment). Decreases in proliferation-related genes were confirmed at the protein level for cyclin A2, BuRB1, cdc2, Pttg, and TPX-2. Interestingly, the proteins downregulated in tumors were similarly downregulated in vorozole-treated normal rat mammary epithelium. Finally, decreased expression of known estrogen-responsive genes (including TFF, 1,3, progesterone receptor, etc.) were decreased in the animal model. These studies demonstrate that gene expression changes (pathways and individual genes) are similar in humans and the rat model.
C1 [Lu, Yan; You, Ming; Liu, Pengyuan; Vedell, Peter T.] Med Coll Wisconsin, Dept Physiol, Milwaukee, WI 53226 USA.
[Lu, Yan; You, Ming; Liu, Pengyuan; Vedell, Peter T.] Med Coll Wisconsin, Dept Pharmacol, Milwaukee, WI 53226 USA.
[Lu, Yan; You, Ming; Liu, Pengyuan; Vedell, Peter T.] Med Coll Wisconsin, Ctr Canc, Milwaukee, WI 53226 USA.
[Ghazoui, Zara] Inst Canc Res, Breakthrough Breast Canc Res, London SW3 6JB, England.
[Wen, Weidong] Washington Univ, Sch Med, Dept Surg, St Louis, MO 63110 USA.
[Bode, Ann M.] Hormel Inst, Austin, MN USA.
[Grubbs, Clinton J.] Univ Alabama Birmingham, Dept Surg, Birmingham, AL 35294 USA.
[Lubet, Ronald A.] NCI, Chemoprevent Agent Dev Res Grp, Rockville, MD USA.
RP Grubbs, CJ (reprint author), Univ Alabama Birmingham, 1670 Univ Blvd,Volker Hall G-78-D Box 800, Birmingham, AL 35294 USA.
EM clintongrubbs@uabmc.edu
FU National Cancer Institute [HHSN261200433001C, HHSN261200433008C]
FX This study was supported by National Cancer Institute, contract number
HHSN261200433001C and HHSN261200433008C.
NR 33
TC 5
Z9 5
U1 0
U2 1
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1940-6207
EI 1940-6215
J9 CANCER PREV RES
JI Cancer Prev. Res.
PD NOV
PY 2013
VL 6
IS 11
BP 1151
EP 1161
DI 10.1158/1940-6207.CAPR-13-0126
PG 11
WC Oncology
SC Oncology
GA 259IB
UT WOS:000327519500001
PM 24067424
ER
PT J
AU Safaeian, M
Porras, C
Pan, YJ
Kreimer, A
Schiller, JT
Gonzalez, P
Lowy, DR
Wacholder, S
Schiffman, M
Rodriguez, AC
Herrero, R
Kemp, T
Shelton, G
Quint, W
van Doorn, LJ
Hildesheim, A
Pinto, LA
AF Safaeian, Mahboobeh
Porras, Carolina
Pan, Yuanji
Kreimer, Aimee
Schiller, John T.
Gonzalez, Paula
Lowy, Douglas R.
Wacholder, Sholom
Schiffman, Mark
Rodriguez, Ana C.
Herrero, Rolando
Kemp, Troy
Shelton, Gloriana
Quint, Wim
van Doorn, Leen-Jan
Hildesheim, Allan
Pinto, Ligia A.
CA CVT Grp
TI Durable Antibody Responses Following One Dose of the Bivalent Human
Papillomavirus L1 Virus-Like Particle Vaccine in the Costa Rica Vaccine
Trial
SO CANCER PREVENTION RESEARCH
LA English
DT Article
ID HUMORAL IMMUNITY; IMMUNOGENICITY; SAFETY; HUMAN-PAPILLOMAVIRUS-16;
PROTECTION; DURATION; AVIDITY; CELLS; ASSAY; PCR
AB The Costa Rica HPV16/18 Vaccine Trial (CVT) showed that four-year vaccine efficacy against 12-month HPV16/18 persistent infection was similarly high among women who received one, two, or the recommended three doses of the bivalent HPV16/18 L1 virus-like particle (VLP) vaccine. Live-attenuated viral vaccines, but not simple-subunit vaccines, usually induce durable lifelong antibody responses after a single dose. It is unclear whether noninfectious VLP vaccines behave more like live-virus or simple-subunit vaccines in this regard. To explore the likelihood that efficacy will persist longer term, we investigated the magnitude and durability of antibodies to this vaccine by measuring HPV16- and HPV18-specific antibodies by VLP-ELISA using serum from enrollment, vaccination, and annual visits through four years in four vaccinated groups; one-dose (n = 78), two-doses separated by one month (n = 140), two doses separated by six months (n = 52), and three scheduled doses (n = 120, randomly selected). We also tested enrollment sera from n 113 HPV16- or HPV18 L1-seropositive women prevaccination, presumably from natural infection. At four years, 100% of women in all groups remained HPV16/18 seropositive; both HPV16/18 geometric mean titers (GMT) among the extended two-dose group were non-inferior to the three-dose group, and ELISA titers were highly correlated with neutralization titers in all groups. Compared with the natural infection group, HPV16/18 GMTs were, respectively, at least 24 and 14 times higher among the two-dose and 9 and 5 times higher among one-dose vaccinees. Antibody levels following one-dose remained stable from month 6 through month 48. Results raise the possibility that even a single dose of HPVVLPs will induce long-term protection.
C1 [Safaeian, Mahboobeh; Pan, Yuanji; Kreimer, Aimee; Schiller, John T.; Lowy, Douglas R.; Wacholder, Sholom; Schiffman, Mark; Kemp, Troy; Shelton, Gloriana; Hildesheim, Allan; Pinto, Ligia A.] NCI, NIH, Bethesda, MD 20892 USA.
[Quint, Wim; van Doorn, Leen-Jan] DDL Diagnost Lab, Voorburg, Netherlands.
[Gonzalez, Paula; Herrero, Rolando] Int Agcy Res Canc, Prevent & Implementat Grp, F-69372 Lyon, France.
RP Safaeian, M (reprint author), NCI, Div Canc Epidemiol & Genet, Infect & Immunoepidemiol Branch, 9609 Med Ctr Dr,Rm 6-E224,MSC 9767, Bethesda, MD 20892 USA.
EM safaeianm@mail.nih.gov
RI Katki, Hormuzd/B-4003-2015; Hildesheim, Allan/B-9760-2015
OI Hildesheim, Allan/0000-0003-0257-2363
FU NCI [N01-CP-11005]; National Institutes of Health Office of Research on
Women's Health; Ministry of Health of Costa Rica
FX The trial is sponsored and funded by the NCI (contract N01-CP-11005),
with funding support from the National Institutes of Health Office of
Research on Women's Health, and done with the support from the Ministry
of Health of Costa Rica. Vaccine was provided for our trial by
GlaxoSmithKline Biologicals, under a Clinical Trials Agreement with the
NCI. GlaxoSmithKline also provided support for aspects of the trial
associated with regulatory submission needs of the company under U.S.
Food and Drug Administration BB-IND 7920.
NR 30
TC 87
Z9 88
U1 0
U2 9
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1940-6207
EI 1940-6215
J9 CANCER PREV RES
JI Cancer Prev. Res.
PD NOV
PY 2013
VL 6
IS 11
BP 1242
EP 1250
DI 10.1158/1940-6207.CAPR-13-0203
PG 9
WC Oncology
SC Oncology
GA 259IB
UT WOS:000327519500009
PM 24189371
ER
PT J
AU Ambudkar, IS
AF Ambudkar, Indu S.
TI TRPC1: Getting physical in space
SO CELL CYCLE
LA English
DT Editorial Material
ID SKELETAL-MUSCLE; CELL-CYCLE; MICROGRAVITY
C1 Natl Inst Dent & Craniofacial Res, Secretory Physiol Sect, Mol Physiol & Therapeut Branch, NIH, Bethesda, MD USA.
RP Ambudkar, IS (reprint author), Natl Inst Dent & Craniofacial Res, Secretory Physiol Sect, Mol Physiol & Therapeut Branch, NIH, Bethesda, MD USA.
EM indu.ambudkar@nih.gov
NR 8
TC 0
Z9 0
U1 0
U2 4
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 1538-4101
EI 1551-4005
J9 CELL CYCLE
JI Cell Cycle
PD NOV 1
PY 2013
VL 12
IS 21
BP 3355
EP 3356
DI 10.4161/cc.26637
PG 2
WC Cell Biology
SC Cell Biology
GA 257JZ
UT WOS:000327381000006
PM 24091530
ER
PT J
AU Templeton, JP
Wang, XD
Freeman, NE
Ma, ZW
Lu, A
Hejtmancik, F
Geisert, EE
AF Templeton, Justin P.
Wang, XiangDi
Freeman, Natalie E.
Ma, Zhiwei
Lu, Anna
Hejtmancik, Fielding
Geisert, Eldon E.
TI A crystallin gene network in the mouse retina
SO EXPERIMENTAL EYE RESEARCH
LA English
DT Article
DE crystallin; BXD strains; promoter analysis; quantitative trait loci;
transcription factor
ID BZIP TRANSCRIPTION FACTOR; ALPHA-B-CRYSTALLIN; LENS DEVELOPMENT; L-MAF;
MICROARRAY ANALYSIS; OXIDATIVE STRESS; DELTA-CRYSTALLIN; A-CRYSTALLIN;
RAT RETINA; EXPRESSION
AB The present study was designed to examine the regulation of crystallin genes and protein in the mouse retina using the BXD recombinant inbred (RI) strains. Illumina Sentrix BeadChip Arrays (MouseWG-6v2) were used to analyze mRNA levels in 75 BXD RI strains along with the parental strains (C57Bl/6J and DBA/2J), and the reciprocal crosses in the Hamilton Eye Institute (HEI) Retina Dataset (www.genenetwork.org). Protein levels were investigated using immunoblots to quantify levels of proteins and indirect immunohistochemistry to define the distribution of protein. Algorithms in the Genomatix program were used to identify transcription factor binding sites common to the regulatory sequences in the 5' regions of co-regulated set of crystallin and other genes as compared to a set of control genes. As subset of genes, including many encoding lens crystallins is part of a tightly co-regulated network that is active in the retina. Expression of this crystallin network appears to be binary in nature, being expressed either at relatively low levels or being highly upregulated. Relative to a control set of genes, the 5' regulatory sequences of the crystallin network genes show an increased frequency of a set of common transcription factor-binding sites, the most common being those of the Maf family. Chromatin immunoprecipitation of human lens epithelial cells (HLEC) and rat retinal ganglion cells (RGC) confirmed the functionality of these sites, showing that MafA binds the predicted sites of CRYGA and CRYGD in HLE and CRYAB, CRYGA, CRYBA1, and CRYBB3 in RGC cells. In the retina there is a highly correlated group of genes containing many members of the alpha- beta- and gamma-crystallin families. These genes can be dramatically upregulated in the retina. One transcription factor that appears to be involved in this coordinated expression is the MAF family transcription of factors associated with both lens and extralenticular expression of crystallin genes. (C) 2013 Published by Elsevier Ltd.
C1 [Templeton, Justin P.; Wang, XiangDi; Freeman, Natalie E.; Geisert, Eldon E.] Univ Tennessee, Dept Ophthalmol, Hlth Sci Ctr, Memphis, TN 38163 USA.
[Ma, Zhiwei; Lu, Anna; Hejtmancik, Fielding] NEI, Ophthalm Genet & Visual Funct Branch, NIH, Bethesda, MD 20892 USA.
RP Geisert, EE (reprint author), Univ Tennessee, Dept Ophthalmol, Hlth Sci Ctr, 930 Madison Av,Suite 731, Memphis, TN 38163 USA.
EM egeisert@uthsc.edu
FU NEI [RO1017841]; Research to Prevent Blindness (UTHSC)
FX This work is supported by NEI grant RO1017841 and an Unrestricted Grant
from Research to Prevent Blindness (UTHSC).
NR 43
TC 12
Z9 12
U1 0
U2 3
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0014-4835
EI 1096-0007
J9 EXP EYE RES
JI Exp. Eye Res.
PD NOV
PY 2013
VL 116
BP 129
EP 140
DI 10.1016/j.exer.2013.08.001
PG 12
WC Ophthalmology
SC Ophthalmology
GA 259YP
UT WOS:000327562500015
PM 23978599
ER
PT J
AU Crown, KN
Savytskyy, OP
Malik, SB
Logsdon, J
Williams, RS
Tainer, JA
Zolan, ME
AF Crown, K. Nicole
Savytskyy, Oleksandr P.
Malik, Shehre-Banoo
Logsdon, John
Williams, R. Scott
Tainer, John A.
Zolan, Miriam E.
TI A Mutation in the FHA Domain of Coprinus cinereus Nbs1 Leads to
Spo11-Independent Meiotic Recombination and Chromosome Segregation
SO G3-GENES GENOMES GENETICS
LA English
DT Article
DE MRN complex; Coprinus cinereus; recombination; DNA replication; meiosis
ID DOUBLE-STRAND BREAKS; DNA-DAMAGE RESPONSE; MULTIPLE SEQUENCE ALIGNMENT;
HOLLIDAY JUNCTIONS; MRE11 COMPLEX; HOMOLOGOUS RECOMBINATION;
SACCHAROMYCES-CEREVISIAE; FISSION YEAST; CROSSING-OVER; MRE11/RAD50/NBS1
COMPLEX
AB Nbs1, a core component of the Mre11-Rad50-Nbs1 complex, plays an essential role in the cellular response to DNA double-strand breaks (DSBs) and poorly understood roles in meiosis. We used the basidiomycete Coprinus cinereus to examine the meiotic roles of Nbs1. We identified the C. cinereus nbs1 gene and demonstrated that it corresponds to a complementation group previously known as rad3. One allele, nbs1-2, harbors a point mutation in the Nbs1 FHA domain and has a mild spore viability defect, increased frequency of meiosis I nondisjunction, and an altered crossover distribution. The nbs1-2 strain enters meiosis with increased levels of phosphorylated H2AX, which we hypothesize represent unrepaired DSBs formed during premeiotic replication. In nbs1-2, there is no apparent induction of Spo11-dependent DSBs during prophase. We propose that replication-dependent DSBs, resulting from defective replication fork protection and processing by the Mre11-Rad50-Nbs1 complex, are competent to form meiotic crossovers in C. cinereus, and that these crossovers lead to high levels of faithful chromosome segregation. In addition, although crossover distribution is altered in nbs1-2, the majority of crossovers were found in subtelomeric regions, as in wild-type. Therefore, the location of crossovers in C. cinereus is maintained when DSBs are induced via a Spo11-independent mechanism.
C1 [Crown, K. Nicole; Savytskyy, Oleksandr P.; Zolan, Miriam E.] Indiana Univ, Dept Biol, Bloomington, IN 47405 USA.
[Malik, Shehre-Banoo; Logsdon, John] Univ Iowa, Dept Biol, Iowa City, IA 52242 USA.
[Williams, R. Scott] NIEHS, Res Triangle Pk, NC 27709 USA.
[Tainer, John A.] Scripps Res Inst, La Jolla, CA 92037 USA.
RP Zolan, ME (reprint author), Indiana Univ, Dept Biol, 1001 East 3rd St, Bloomington, IN 47405 USA.
EM mzolan@indiana.edu
RI Williams, Robert/A-6059-2015
FU National Institutes of Health (NIH); NIH [GM43930]; Indiana MetaCyt
Initiative of Indiana University; Lilly Endowment, Inc.; NSF
[MCB-0216702]; Canadian Institute for Advanced Research Integrated
Microbial Biodiversity Program; National Cancer Institute [CA117638,
CA92584]; United States NIH, National Institute of Environmental Health
Sciences (NIEHS) [1Z01ES102765-01]
FX We thank Pat Pukkila, Soni Lacefield, and Claire Burns for critical
reading of the manuscript, and Elizabeth Housworth for help and advice
early in the course of these experiments. K.N.C. was supported in part
by the National Institutes of Health (NIH) Genetics Training Grant to
Indiana University. M.Z. provided laboratory support with NIH grant
GM43930 and the Indiana MetaCyt Initiative of Indiana University, which
is funded in part by a major grant from the Lilly Endowment, Inc. J.M.L.
and S. B. M. were supported by the NSF grant MCB-0216702 (to J.M.L.). S.
B. M. was supported by a Junior Fellowship from the Canadian Institute
for Advanced Research Integrated Microbial Biodiversity Program. J.A.T.
was supported by National Cancer Institute grants CA117638 and CA92584.
This research was supported in part by the intramural research program
of the United States NIH, National Institute of Environmental Health
Sciences (NIEHS) (1Z01ES102765-01 to R.S.W.).
NR 104
TC 5
Z9 5
U1 2
U2 11
PU GENETICS SOC AM
PI BETHESDA
PA 9650 ROCKVILLE AVE, BETHESDA, MD 20814 USA
SN 2160-1836
J9 G3-GENES GENOM GENET
JI G3-Genes Genomes Genet.
PD NOV
PY 2013
VL 3
IS 11
BP 1927
EP 1943
DI 10.1534/g3.113.007906
PG 17
WC Genetics & Heredity
SC Genetics & Heredity
GA 255LY
UT WOS:000327241900004
PM 24062528
ER
PT J
AU Hong, FX
Simon, R
AF Hong, Fangxin
Simon, Richard
TI Run-In Phase III Trial Design With Pharmacodynamics Predictive
Biomarkers
SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Article
ID RANDOMIZED CLINICAL-TRIALS; DISCONTINUATION DESIGN; PHYSICIANS HEALTH;
CARCINOMA CELLS; DENDRITIC CELLS; EFFICIENCY; PLACEBO; FUSIONS; BREAST
AB Developments in biotechnology have stimulated the use of predictive biomarkers to identify patients who are likely to benefit from a targeted therapy. Several randomized phase III designs have been introduced for development of a targeted therapy using a diagnostic test. Most such designs require biomarkers measured before treatment. In many cases, it has been very difficult to identify such biomarkers. Promising candidate biomarkers can sometimes be effectively measured after a short run-in period on the new treatment.
We introduce a new design for phase III trials with a candidate predictive pharmacodynamic biomarker measured after a short run-in period. Depending on the therapy and the biomarker performance, the trial would either randomize all patients but perform a separate analysis on the biomarker-positive patients or only randomize marker-positive patients after the run-in period. We evaluate the proposed design compared with the conventional phase III design and discuss how to design a run-in trial based on phase II studies.
The proposed design achieves a major sample size reduction compared with the conventional randomized phase III design in many cases when the biomarker has good sensitivity (0.7) and specificity (0.7). This requires that the biomarker be measured accurately and be indicative of drug activity. However, the proposed design loses some of its advantage when the proportion of potential responders is large (> 50%) or the effect on survival from run-in period is substantial.
Incorporating a pharmacodynamic biomarker requires careful consideration but can expand the capacity of clinical trials to personalize treatment decisions and enhance therapeutics development.
C1 [Hong, Fangxin] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA.
[Hong, Fangxin] Harvard Univ, Sch Publ Hlth, Dana Farber Canc Inst, Dept Computat Biol, Boston, MA 02115 USA.
[Simon, Richard] NCI, Biometr Res Branch, Bethesda, MD 20892 USA.
RP Simon, R (reprint author), NCI, Biometr Res Branch, Bethesda, MD 20892 USA.
EM rsimon@mail.nih.gov
FU Department of Biostatistics and Computational Biology Research Scientist
Fund
FX This work was supported by the Department of Biostatistics and
Computational Biology Research Scientist Fund (to FH).
NR 20
TC 2
Z9 2
U1 0
U2 1
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0027-8874
EI 1460-2105
J9 JNCI-J NATL CANCER I
JI JNCI-. Natl. Cancer Inst.
PD NOV
PY 2013
VL 105
IS 21
BP 1628
EP 1633
DI 10.1093/jnci/djt265
PG 6
WC Oncology
SC Oncology
GA 251ZL
UT WOS:000326973900009
PM 24096624
ER
PT J
AU Polley, MYC
Freidlin, B
Korn, EL
Conley, BA
Abrams, JS
McShane, LM
AF Polley, Mei-Yin C.
Freidlin, Boris
Korn, Edward L.
Conley, Barbara A.
Abrams, Jeffrey S.
McShane, Lisa M.
TI Statistical and Practical Considerations for Clinical Evaluation of
Predictive Biomarkers
SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Editorial Material
ID CELL LUNG-CANCER; RANDOMIZED PHASE-III; ADJUVANT TEMOZOLOMIDE;
MAINTENANCE THERAPY; BREAST-CANCER; GLIOBLASTOMA; DESIGN; CETUXIMAB;
EGFR; CHEMOTHERAPY
AB Predictive biomarkers to guide therapy for cancer patients are a cornerstone of precision medicine. Discussed herein are considerations regarding the design and interpretation of such predictive biomarker studies. These considerations are important for both planning and interpreting prospective studies and for using specimens collected from completed randomized clinical trials. Specific issues addressed are differentiation between qualitative and quantitative predictive effects, challenges due to sample size requirements for predictive biomarker assessment, and consideration of additional factors relevant to clinical utility assessment, such as toxicity and cost of new therapies as well as costs and potential morbidities associated with routine use of biomarker-based tests.
C1 [Polley, Mei-Yin C.; Freidlin, Boris; Korn, Edward L.; McShane, Lisa M.] NCI, Biometr Res Branch, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA.
[Conley, Barbara A.] NCI, Canc Diag Program, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA.
[Abrams, Jeffrey S.] NCI, Canc Treatment & Evaluat Program, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA.
RP Polley, MYC (reprint author), NCI, Biometr Res Branch, NIH, 9609 Med Ctr Dr,Rm 5W638,MSC 9735, Bethesda, MD 20892 USA.
EM polleymc@mail.nih.gov
NR 28
TC 29
Z9 29
U1 0
U2 6
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0027-8874
EI 1460-2105
J9 JNCI-J NATL CANCER I
JI JNCI-. Natl. Cancer Inst.
PD NOV
PY 2013
VL 105
IS 22
BP 1677
EP 1683
DI 10.1093/jnci/djt282
PG 7
WC Oncology
SC Oncology
GA 259PO
UT WOS:000327539000004
PM 24136891
ER
PT J
AU Zhu, CS
Pinsky, PF
Kramer, BS
Prorok, PC
Purdue, MP
Berg, CD
Gohagan, JK
AF Zhu, Claire S.
Pinsky, Paul F.
Kramer, Barnett S.
Prorok, Philip C.
Purdue, Mark P.
Berg, Christine D.
Gohagan, John K.
TI The Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial and
Its Associated Research Resource
SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE
LA English
DT Review
ID FORCE RECOMMENDATION STATEMENT; NURSES HEALTH; MORTALITY; COSTS
AB The Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial is a large-scale research effort conducted by the National Cancer Institute. PLCO offers an example of coordinated research by both the extramural and intramural communities of the National Institutes of Health. The purpose of this article is to describe the PLCO research resource and how it is managed and to assess the productivity and the costs associated with this resource. Such an in-depth analysis of a single large-scale project can shed light on questions such as how large-scale projects should be managed, what metrics should be used to assess productivity, and how costs can be compared with productivity metrics. A comprehensive publication analysis identified 335 primary research publications resulting from research using PLCO data and biospecimens from 2000 to 2012. By the end of 2012, a total of 9679 citations (excluding self-citations) have resulted from this body of research publications, with an average of 29.7 citations per article, and an h index of 45, which is comparable with other large-scale studies, such as the Nurses Health Study. In terms of impact on public health, PLCO trial results have been used by the US Preventive Services Task Force in making recommendations concerning prostate and ovarian cancer screening. The overall cost of PLCO was $454 million over 20 years, adjusted to 2011 dollars, with approximately $37 million for the collection, processing, and storage of biospecimens, including blood samples, buccal cells, and pathology tissues.
C1 [Zhu, Claire S.; Pinsky, Paul F.; Kramer, Barnett S.; Prorok, Philip C.; Berg, Christine D.] NCI, Early Detect Res Grp, Canc Prevent Div, Bethesda, MD 20892 USA.
[Purdue, Mark P.] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Gohagan, John K.] NIH, Off Dis Prevent, Bethesda, MD 20892 USA.
RP Pinsky, PF (reprint author), NCI, Early Detect Res Grp, Canc Prevent Div, NIH, Bethesda, MD 20892 USA.
EM pinskyp@mail.nih.gov
RI Berg , Christine/K-1047-2014; Purdue, Mark/C-9228-2016
OI Purdue, Mark/0000-0003-1177-3108
NR 18
TC 8
Z9 8
U1 0
U2 8
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0027-8874
EI 1460-2105
J9 JNCI-J NATL CANCER I
JI JNCI-. Natl. Cancer Inst.
PD NOV
PY 2013
VL 105
IS 22
BP 1684
EP 1693
DI 10.1093/jnci/djt281
PG 10
WC Oncology
SC Oncology
GA 259PO
UT WOS:000327539000005
PM 24115361
ER
PT J
AU Tarasova, VD
Trepp-Carrasco, AG
Thompson, R
Recker, RR
Chong, WH
Collins, MT
Armas, LAG
AF Tarasova, Valentina D.
Trepp-Carrasco, Alejandro G.
Thompson, Robert
Recker, Robert R.
Chong, William H.
Collins, Michael T.
Armas, Laura A. G.
TI Successful Treatment of Tumor-Induced Osteomalacia due to an
Intracranial Tumor by Fractionated Stereotactic Radiotherapy
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID PHOSPHATURIC MESENCHYMAL TUMORS; ONCOGENIC OSTEOMALACIA; LOCALIZATION;
VARIANT
AB Context: Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome, characterized by tumor secretion of fibroblast growth factor-23 (FGF23) causing hypophosphatemia due to renal phosphate wasting. TIO is usually caused by small, benign, difficult-to-localize, mesenchymal tumors. Although surgery with wide excision of tumor borders is considered the "gold standard" for definitive therapy, it can be associated with considerable morbidity depending on the location. To date, radiation therapy has not been considered as an effective treatment modality in TIO.
Objective: A 67-year-old female presented with multiple nontraumatic fractures, progressive bone pain, and muscle weakness for 4 years. She was found to have biochemical evidence of urinary phosphate wasting with low serum phosphorus, low-normal serum calcium, normal 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D, and high serum FGF23 levels. TIO was diagnosed. Selective venous sampling for FGF23 confirmed that a 1.7-cm left frontal mass, radiographically similar to a meningioma, was the causative tumor. She declined surgery due to fear of complications and instead underwent fractionated stereotactic radiotherapy for 6 weeks.
Results: In less than 4 years after radiation therapy, she was successfully weaned off phosphorus and calcitriol, starting from 2 g of oral phosphorus daily and 1 mu g of calcitriol daily. Her symptoms have resolved, and she has not had any new fractures.
Conclusions: Stereotactic radiotherapy was an effective treatment modality for TIO in our patient. Fractionated stereotactic radiation therapy represents an alternative to surgery for patients with TIO who are not surgical candidates or who decline surgery.
C1 [Tarasova, Valentina D.; Trepp-Carrasco, Alejandro G.; Recker, Robert R.; Armas, Laura A. G.] Creighton Univ, Omaha, NE 68131 USA.
[Thompson, Robert] Univ Nebraska Med Ctr, Omaha, NE 68198 USA.
[Chong, William H.; Collins, Michael T.] NIH, Bethesda, MD 20892 USA.
RP Tarasova, VD (reprint author), Creighton Univ, 601 North 30th St,Suite 5766, Omaha, NE 68131 USA.
EM tarasova.md@gmail.com; larmas@creighton.edu
FU Intramural NIH HHS [ZIA DE000649-19]
NR 16
TC 3
Z9 3
U1 0
U2 3
PU ENDOCRINE SOC
PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0021-972X
EI 1945-7197
J9 J CLIN ENDOCR METAB
JI J. Clin. Endocrinol. Metab.
PD NOV
PY 2013
VL 98
IS 11
BP 4267
EP 4272
DI 10.1210/jc.2013-2528
PG 6
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 254QP
UT WOS:000327180700032
PM 24014621
ER
PT J
AU Brown, RJ
Cochran, E
Gorden, P
AF Brown, Rebecca J.
Cochran, Elaine
Gorden, Phillip
TI Metreleptin Improves Blood Glucose in Patients With Insulin Receptor
Mutations
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID RABSON-MENDENHALL-SYNDROME; DEPENDENT DIABETES-MELLITUS;
LEPTIN-REPLACEMENT THERAPY; CALORIC RESTRICTION; HEPATIC STEATOSIS;
WEIGHT-LOSS; RESISTANCE; LIPODYSTROPHY; DYSFUNCTION; MECHANISMS
AB Context: Rabson-Mendenhall syndrome (RMS) is caused by mutations of the insulin receptor and results in extreme insulin resistance and dysglycemia. Hyperglycemia in RMS is very difficult to treat, and patients are at risk for early morbidity and mortality from complications of diabetes.
Objective: Our objective was to study 1-year effects of recombinant human methionyl leptin (metreleptin) in 5 patients with RMS and 10-year effects in 2 of these patients.
Design and Setting: We conducted an open-label nonrandomized study at the National Institutes of Health.
Patients: Patients were adolescents with RMS and poorly controlled diabetes.
Intervention: Two patients were treated with escalating doses (0.02 up to 0.22 mg/kg/d) of metreleptin for 10 years, including 3 cycles of metreleptin withdrawal and reinitiation. In all 5 patients, 1-year effects of metreleptin (0.22 mg/kg/d) were studied.
Outcome Measures: Hemoglobin A1c (HbA1c) and body mass index (BMI) z-scores were evaluated every 6 months.
Results: HbA1c decreased from 11.4% +/- 1.1% at baseline to 9.3% +/- 1.9% after 6 months and 9.7% +/- 1.6% after 12 months of metreleptin (P = .007). In patients treated for 10 years, HbA1c declined with each cycle of metreleptin and rose with each withdrawal. BMI z-scores declined from -1.4 +/- 1.8 at baseline, to -2.6 +/- 1.6 after 12 months of metreleptin (P = .0006). Changes in BMI z-score correlated with changes in HbA1c (P < .0001).
Conclusions: Metreleptin treatment for 12 months was associated with a 1.7% reduction in HbA1c; part of this improvement was likely mediated via decreased BMI. Metreleptin is a promising treatment option for RMS, but additional therapies are needed to achieve HbA1c targets.
C1 [Brown, Rebecca J.; Cochran, Elaine; Gorden, Phillip] NIDDK, Diabet Endocrinol & Obes Branch, NIH, Bethesda, MD 20892 USA.
RP Brown, RJ (reprint author), Bldg 10 CRC,Room 6-5942,10 Ctr Dr, Bethesda, MD 20892 USA.
EM brownrebecca@mail.nih.gov
FU intramural research program of the National Institute of Diabetes and
Digestive and Kidney Diseases
FX This work was supported by the intramural research program of the
National Institute of Diabetes and Digestive and Kidney Diseases.
NR 40
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Z9 7
U1 2
U2 2
PU ENDOCRINE SOC
PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0021-972X
EI 1945-7197
J9 J CLIN ENDOCR METAB
JI J. Clin. Endocrinol. Metab.
PD NOV
PY 2013
VL 98
IS 11
BP E1749
EP E1756
DI 10.1210/jc.2013-2317
PG 8
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 254QP
UT WOS:000327180700007
PM 23969187
ER
PT J
AU Muniyappa, R
Warren, MA
Zhao, XC
Aney, SC
Courville, AB
Chen, KY
Brychta, RJ
Germain-Lee, EL
Weinstein, LS
Skarulis, MC
AF Muniyappa, Ranganath
Warren, Mary A.
Zhao, Xiongce
Aney, Sara C.
Courville, Amber B.
Chen, Kong Y.
Brychta, Robert J.
Germain-Lee, Emily L.
Weinstein, Lee S.
Skarulis, Monica C.
TI Reduced Insulin Sensitivity in Adults With Pseudohypoparathyroidism Type
1a
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID RESISTANCE; DEFICIENCY; ALPHA; G(S)ALPHA; OBESITY; GENE; MASS
AB Context: Disruption of theGs beta maternal allele leads to severe obesityandinsulin resistance in miceand early-onset obesity in patients with pseudohypoparathyroidism (PHP) type 1a. However, insulin resistance and glucose metabolism have not been systematically characterized in patients with PHP1a.
Objective, Design, and Setting: In a cross-sectional, case-control study, we examined insulin sensitivity, beta-cell function, energy expenditure (EE), and sympathetic nervous system activity in adults with PHP1a.
Study Participants: PHP1a patients (n = 8) and healthy control subjects (n = 24) matched for age (41 +/- 7 vs 41 +/- 7 years [mean +/- SD]), gender, and percent body fat.
Methods: Insulin sensitivity (SI), acute insulin response to glucose, and disposition index were assessed during a frequently sampled iv glucose tolerance test. Oral glucose insulin sensitivity (OGIS) was measured during a mixed meal. EE was measured using whole-room indirect calorimetry. Body composition was assessed via dual-energy x-ray absorptiometry and sympathetic nervous system activity by measuring 24-hour urinary catecholamine concentrations.
Results: PHP1a patients were less insulin-sensitive than their matched controls based uon SI and OGIS. Nondiabetic PHP1a patients tended to have a lower SI (P=.09) and reduced OGIS (P =.03). Disposition index, a composite measure of beta-cell function, also tended to be lower in patients (P =.07). Total caloric intake, resting EE, total EE, meal-induced thermogenesis, and 24-hour urinary catecholamine concentrations were not significantly different between the groups.
Conclusions: Adults with PHP-1a have reduced insulin sensitivity compared with their matched controls that may contribute to the pathogenesis of glucose intolerance and diabetes in these patients.
C1 [Muniyappa, Ranganath; Warren, Mary A.; Zhao, Xiongce; Aney, Sara C.; Chen, Kong Y.; Brychta, Robert J.; Skarulis, Monica C.] NIDDK, Diabet Endocrinol & Obes Branch, NIH, Bethesda, MD 20892 USA.
[Weinstein, Lee S.] NIDDK, Metab Dis Branch, NIH, Bethesda, MD 20892 USA.
[Courville, Amber B.] NIH, Ctr Clin, Bethesda, MD 20892 USA.
[Germain-Lee, Emily L.] Johns Hopkins Univ, Sch Med, Albright Clin, Kennedy Krieger Inst, Baltimore, MD 21205 USA.
Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21205 USA.
RP Skarulis, MC (reprint author), NIDDK, Clin Endocrine Sect, Diabet Endocrinol & Obes Branch, NIH,CRC, 10 Ctr Dr MSC 1613,Bldg 10,Room 6-3940, Bethesda, MD 20892 USA.
EM monicas@intra.niddk.nih.gov
OI Chen, Kong/0000-0002-0306-1904
FU Intramural Research Programs of the National Institute of Diabetes and
Digestive and Kidney Diseases; National Institutes of Health; U.S. Food
and Drug Administration Orphan Products Development [R01 FD-R-002568]
FX This work was supported by the Intramural Research Programs of the
National Institute of Diabetes and Digestive and Kidney Diseases,
National Institutes of Health, and U. S. Food and Drug Administration
Orphan Products Development Grant R01 FD-R-002568 (to E. L. G.-L.).
NR 19
TC 10
Z9 10
U1 0
U2 7
PU ENDOCRINE SOC
PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0021-972X
EI 1945-7197
J9 J CLIN ENDOCR METAB
JI J. Clin. Endocrinol. Metab.
PD NOV
PY 2013
VL 98
IS 11
BP E1796
EP E1801
DI 10.1210/jc.2013-1594
PG 6
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 254QP
UT WOS:000327180700014
PM 24030943
ER
PT J
AU Joiner, WM
Cavanaugh, J
FitzGibbon, EJ
Wurtz, RH
AF Joiner, Wilsaan M.
Cavanaugh, James
FitzGibbon, Edmond J.
Wurtz, Robert H.
TI Corollary discharge contributes to perceived eye location in monkeys
SO JOURNAL OF NEUROPHYSIOLOGY
LA English
DT Article
DE saccade; vision; stability; monkey
ID BRAIN-STEM TELLS; VISUAL-STABILITY; FRONTAL-CORTEX; SUPERIOR COLLICULUS;
PARIETAL CORTEX; SIGNALS SENT; MOVEMENTS; FIELD; REPRESENTATION;
POSITION
AB Despite saccades changing the image on the retina several times per second, we still perceive a stable visual world. A possible mechanism underlying this stability is that an internal retinotopic map is updated with each saccade, with the location of objects being compared before and after the saccade. Psychophysical experiments have shown that humans derive such location information from a corollary discharge (CD) accompanying saccades. Such a CD has been identified in the monkey brain in a circuit extending from superior colliculus to frontal cortex. There is a missing piece, however. Perceptual localization is established only in humans and the CD circuit only in monkeys. We therefore extended measurement of perceptual localization to the monkey by adapting the target displacement detection task developed in humans. During saccades to targets, the target disappeared and then reappeared, sometimes at a different location. The monkeys reported the displacement direction. Detections of displacement were similar in monkeys and humans, but enhanced detection of displacement from blanking the target at the end of the saccade was observed only in humans, not in monkeys. Saccade amplitude varied across trials, but the monkey's estimates of target location did not follow that variation, indicating that eye location depended on an internal CD rather than external visual information. We conclude that monkeys use a CD to determine their new eye location after each saccade, just as humans do.
C1 [Joiner, Wilsaan M.; Cavanaugh, James; FitzGibbon, Edmond J.; Wurtz, Robert H.] NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA.
[Joiner, Wilsaan M.] George Mason Univ, Dept Bioengn, Fairfax, VA 22030 USA.
RP Joiner, WM (reprint author), George Mason Univ, Dept Bioengn, Nguyen Engn Bldg,1G5,4400 Univ Dr,Rm 3800, Fairfax, VA 22030 USA.
EM wjoiner2@gmu.edu
FU National Eye Institute Intramural Research Program at the National
Institutes of Health
FX This work was supported by the National Eye Institute Intramural
Research Program at the National Institutes of Health.
NR 25
TC 8
Z9 8
U1 0
U2 6
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-3077
EI 1522-1598
J9 J NEUROPHYSIOL
JI J. Neurophysiol.
PD NOV
PY 2013
VL 110
IS 10
BP 2402
EP 2413
DI 10.1152/jn.00362.2013
PG 12
WC Neurosciences; Physiology
SC Neurosciences & Neurology; Physiology
GA 257YL
UT WOS:000327423600014
PM 23986562
ER
PT J
AU Van Ryzin, C
AF Van Ryzin, Carol
TI Adrenal Insufficiency: Causes and Prevention of Adrenal Crisis
SO JOURNAL OF PEDIATRIC NURSING-NURSING CARE OF CHILDREN & FAMILIES
LA English
DT Editorial Material
C1 NHGRI, NIH, Bethesda, MD 20892 USA.
RP Van Ryzin, C (reprint author), NHGRI, NIH, Bethesda, MD 20892 USA.
EM Carol.Vanryzin@nih.gov
NR 9
TC 1
Z9 1
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0882-5963
J9 J PEDIATR NURS
JI J. Pediatr. Nurs.
PD NOV-DEC
PY 2013
VL 28
IS 6
BP 620
EP 621
DI 10.1016/j.pedn.2013.08.003
PG 2
WC Nursing; Pediatrics
SC Nursing; Pediatrics
GA 251NX
UT WOS:000326937600027
PM 23994548
ER
PT J
AU Hocking, WG
Tammemagi, MC
Commins, J
Oken, MM
Kvale, PA
Hu, P
Ragard, LR
Riley, TL
Pinsky, P
Beck, TM
Prorok, PC
AF Hocking, William G.
Tammemagi, Martin C.
Commins, John
Oken, Martin M.
Kvale, Paul A.
Hu, Ping
Ragard, Lawrence R.
Riley, Tom L.
Pinsky, Paul
Beck, Thomas M.
Prorok, Philip C.
TI Diagnostic evaluation following a positive lung screening chest
radiograph in the Prostate, Lung, Colorectal, Ovarian (PLCO) Cancer
Screening Trial
SO LUNG CANCER
LA English
DT Article
DE Lung neoplasms; Mortality; Radiography; Screening; Methods; Risk factors
ID SOLITARY PULMONARY NODULES; CLINICAL-PREDICTION MODEL; RANDOMIZED-TRIAL;
PROGNOSIS; MORTALITY; DELAY
AB Lung cancer is the major cause of cancer mortality. One of the aims of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) was to determine if annual screening chest radiographs reduce lung cancer mortality. We enrolled 154,900 individuals, aged 55-74 years; 77,445 were randomized to the intervention arm and received an annual chest radiograph for 3 or 4 years. Participants with a positive screen underwent diagnostic evaluation under guidance of their primary physician. Methods of diagnosis or exclusion of cancer, interval from screen to diagnosis, and factors predicting diagnostic testing were evaluated. One or more positive screens occurred in 17% of participants. Positive screens resulted in biopsy in 3%, with 54% positive for cancer. Biopsy likelihood was associated with a mass, smoking, age, and family history of lung cancer. Diagnostic testing stopped after a chest radiograph or computed tomography/magnetic resonance imaging in over half. After a second or subsequent positive screen, evaluation stopped after comparison to prior radiographs in over half. Of 308 screen-detected cancers, the diagnosis was established by thoracotomy/thoracoscopy in 47.7%, needle biopsy in 27.6%, bronchoscopy in 20.1% and mediastinoscopy in 2.9%. Eighty-four percent of screen-detected lung cancers were diagnosed within 6 months. Diagnostic evaluations following a positive screen were conducted in a timely fashion. Lung cancer was diagnosed by tissue biopsy or cytology in all cases. Lung cancer was excluded during evaluation of positive screening examinations by clinical or radiographic evaluation in all but 1.4% who required a tissue biopsy. (C) 2013 Elsevier Ireland Ltd. All rights reserved.
C1 [Hocking, William G.] Marshfield Clin Fdn Med Res & Educ, Dept Hematol Oncol, Marshfield, WI USA.
[Tammemagi, Martin C.] Brock Univ, Dept Community Hlth Sci, St Catharines, ON L2S 3A1, Canada.
[Commins, John; Riley, Tom L.] Informat Management Serv Inc, Rockville, MD USA.
[Oken, Martin M.] Univ Minnesota, Virginia Piper Canc Inst, Minneapolis, MN USA.
[Kvale, Paul A.] Henry Ford Hlth Syst, Dept Pulm Dis, Detroit, MI USA.
[Hu, Ping; Pinsky, Paul] NCI, Canc Prevent Div, Bethesda, MD 20892 USA.
[Ragard, Lawrence R.] Westat Corp, Rockville, MD USA.
[Beck, Thomas M.] St Lukes Reg Med Ctr, Mt States Tumor Inst, Boise, ID USA.
[Prorok, Philip C.] NCI, Biometry Res Grp, Bethesda, MD 20892 USA.
RP Hocking, WG (reprint author), Dept Oncol Hematol, 1000N Oak Ave, Marshfield, WI 54449 USA.
EM hocking.william@marshfieldclinic.org
OI Hocking, William/0000-0002-0690-3759
FU Division of Cancer Prevention, National Cancer Institute; NIH; DHHS
[NO1-CN-25518]
FX This research was supported by contracts from the Division of Cancer
Prevention, National Cancer Institute, NIH, and DHHS, Contract
#NO1-CN-25518. The NCI participated in trial design and provided
oversight during conduct of the study. Trial Registration:
clinicaltrials.gov identifier: NCT00002540.
NR 24
TC 0
Z9 0
U1 0
U2 4
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0169-5002
EI 1872-8332
J9 LUNG CANCER
JI Lung Cancer
PD NOV
PY 2013
VL 82
IS 2
BP 238
EP 244
DI 10.1016/j.lungcan.2013.07.017
PG 7
WC Oncology; Respiratory System
SC Oncology; Respiratory System
GA 257ED
UT WOS:000327365500008
PM 23993734
ER
PT J
AU Xu, ZY
Bagci, U
Kubler, A
Luna, B
Jain, S
Bishai, WR
Mollura, DJ
AF Xu, Ziyue
Bagci, Ulas
Kubler, Andre
Luna, Brian
Jain, Sanjay
Bishai, William R.
Mollura, Daniel J.
TI Computer-aided detection and quantification of cavitary tuberculosis
from CT scans
SO MEDICAL PHYSICS
LA English
DT Article
DE cavitary tuberculosis; airway tree; computer aided detection;
segmentation; fuzzy connectedness
ID PULMONARY TUBERCULOSIS; ANTITUBERCULOUS THERAPY; LUNG; SEGMENTATION;
DISEASE; IMAGES; TOMOGRAPHY; DEFINITION; DIAGNOSIS; TREE
AB Purpose: To present a computer-aided detection tool for identifying, quantifying, and evaluating tuberculosis (TB) cavities in the infected lungs from computed tomography (CT) scans.
Methods: The authors' proposed method is based on a novel shape-based automated detection algorithm on CT scans followed by a fuzzy connectedness (PC) delineation procedure. In order to assess interaction between cavities and airways, the authors first roughly identified air-filled structures (airway, cavities, esophagus, etc.) by thresholding over Hounsfield unit of CT image. Then, airway and cavity structure detection was conducted within the support vector machine classification algorithm. Once airway and cavities were detected automatically, the authors extracted airway tree using a hybrid multiscale approach based on novel affinity relations within the FC framework and segmented cavities using intensity-based FC algorithm. At final step, the authors refined airway structures within the local regions of PC with finer control. Cavity segmentation results were compared to the reference truths provided by expert radiologists and cavity formation was tracked longitudinally from serial CT scans through shape and volume information automatically determined through the authors' proposed system. Morphological evolution of the cavitary TB were analyzed accordingly with this process. Finally, the authors computed the minimum distance between cavity surface and nearby airway structures by using the linear time distance transform algorithm to explore potential role of airways in cavity formation and morphological evolution.
Results: The proposed methodology was qualitatively and quantitatively evaluated on pulmonary CT images of rabbits experimentally infected with TB, and multiple markers such as cavity volume, cavity surface area, minimum distance from cavity surface to the nearest bronchial-tree, and longitudinal change of these markers (namely, morphological evolution of cavities) were determined precisely. While accuracy of the authors' cavity detection algorithm was 94.61%, airway detection part of the proposed methodology showed even higher performance by 99.8%. Dice similarity coefficients for cavitary segmentation experiments were found to be approximately 99.0% with respect to the reference truths provided by two expert radiologists (blinded to their evaluations). Moreover, the authors noted that volume derived from the authors' segmentation method was highly correlated with those provided by the expert radiologists (R-2 = 0.99757 and R-2 = 0.99496, p <0.001, with respect to the observer 1 and observer 2) with an interobserver agreement of 98%. The authors quantitatively confirmed that cavity formation was positioned by the nearby bronchial-tree after exploring the respective spatial positions based on the minimum distance measurement. In terms of efficiency, the core algorithms take less than 2 min on a linux machine with 3.47 GHz CPU and 24 GB memory.
Conclusion: The authors presented a fully automatic method for cavitary TB detection, quantification, and evaluation. The performance of every step of the algorithm was qualitatively and quantitatively assessed. With the proposed method, airways and cavities were automatically detected and subsequently delineated in high accuracy with heightened efficiency. Furthermore, not only morphological information of cavities were obtained through the authors' proposed framework, but their spatial relation to airways, and longitudinal analysis was also provided to get further insight on cavity formation in tuberculosis disease. To the authors' best of knowledge, this is the first study in computerized analysis of cavitary tuberculosis from CT scans. (C) 2013 American Association of Physicists in Medicine.
C1 [Xu, Ziyue; Bagci, Ulas; Mollura, Daniel J.] NIH, Ctr Infect Dis Imaging CIDI Radiol & Imaging Sci, Bethesda, MD 20892 USA.
[Kubler, Andre; Luna, Brian; Jain, Sanjay; Bishai, William R.] Johns Hopkins Univ, Ctr TB Res, Baltimore, MD 21287 USA.
[Kubler, Andre] Univ London Imperial Coll Sci Technol & Med, Dept Med, London W12 0HS, England.
[Jain, Sanjay] Johns Hopkins Univ, Ctr Infect & Inflammat Imaging Res, Baltimore, MD 21287 USA.
[Bishai, William R.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA.
RP Xu, ZY (reprint author), NIH, Ctr Infect Dis Imaging CIDI Radiol & Imaging Sci, Bldg 10, Bethesda, MD 20892 USA.
EM ziyue.xu@nih.gov
RI Xy, Ziyue/K-9438-2014;
OI Xy, Ziyue/0000-0002-5728-6869; Bagci, Ulas/0000-0001-7379-6829; Luna,
PhD, Brian/0000-0001-6718-4551
FU CIDI, the intramural research program of the National Institute of
Allergy and Infectious Diseases (NIAID); National Institute of
Biomedical Imaging and Bioengineering (NIBIB)
FX This research is supported by CIDI, the intramural research program of
the National Institute of Allergy and Infectious Diseases (NIAID) and
the National Institute of Biomedical Imaging and Bioengineering (NIBIB).
W. R. Bishai acknowledges R01 Al 079590 and the support of Howard Hughes
Medical Institute (HHMI). S. JaM acknowledges the Grant No. DP2
0D006492-01. A. Kubler is funded by internal grant from Imperial College
London, and acknowledges Dr. J. S. Friedland and Dr. P. T. G. Elkington.
NR 39
TC 8
Z9 8
U1 2
U2 7
PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS
PI MELVILLE
PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA
SN 0094-2405
J9 MED PHYS
JI Med. Phys.
PD NOV
PY 2013
VL 40
IS 11
AR 113701
DI 10.1118/1.4824979
PG 14
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 252FZ
UT WOS:000326991800069
PM 24320475
ER
PT J
AU Sobek, S
Dalla Rosa, I
Pommier, Y
Bornholz, B
Kalfalah, F
Zhang, HL
Wiesner, RJ
von Kleist-Retzow, JC
Hillebrand, F
Schaal, H
Mielke, C
Christensen, MO
Boege, F
AF Sobek, Stefan
Dalla Rosa, Ilaria
Pommier, Yves
Bornholz, Beatrice
Kalfalah, Faiza
Zhang, Hongliang
Wiesner, Rudolf J.
von Kleist-Retzow, Juergen-Christoph
Hillebrand, Frank
Schaal, Heiner
Mielke, Christian
Christensen, Morten O.
Boege, Fritz
TI Negative regulation of mitochondrial transcription by mitochondrial
topoisomerase I
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID N-TERMINAL DOMAIN; RNA-POLYMERASE-II; MAMMALIAN MITOCHONDRIA; DNA
NUCLEOIDS; MTDNA; CELLS; ACTIVATION; NUCLEAR; TFAM; REPLICATION
AB Mitochondrial topoisomerase I is a genetically distinct mitochondria-dedicated enzyme with a crucial but so far unknown role in the homeostasis of mitochondrial DNA metabolism. Here, we present data suggesting a negative regulatory function in mitochondrial transcription or transcript stability. Deficiency or depletion of mitochondrial topoisomerase I increased mitochondrial transcripts, whereas overexpression lowered mitochondrial transcripts, depleted respiratory complexes I, III and IV, decreased cell respiration and raised superoxide levels. Acute depletion of mitochondrial topoisomerase I triggered neither a nuclear mito-biogenic stress response nor compensatory topoisomerase II beta upregulation, suggesting the concomitant increase in mitochondrial transcripts was due to release of a local inhibitory effect. Mitochondrial topoisomerase I was co-immunoprecipitated with mitochondrial RNA polymerase. It selectively accumulated and rapidly exchanged at a subset of nucleoids distinguished by the presence of newly synthesized RNA and/or mitochondrial RNA polymerase. The inactive Y559F-mutant behaved similarly without affecting mitochondrial transcripts. In conclusion, mitochondrial topoisomerase I dampens mitochondrial transcription and thereby alters respiratory capacity. The mechanism involves selective association of the active enzyme with transcriptionally active nucleoids and a direct interaction with mitochondrial RNA polymerase. The inhibitory role of topoisomerase I in mitochondrial transcription is strikingly different from the stimulatory role of topoisomerase I in nuclear transcription.
C1 [Sobek, Stefan; Bornholz, Beatrice; Kalfalah, Faiza; Mielke, Christian; Christensen, Morten O.; Boege, Fritz] Univ Dusseldorf, Fac Med, Inst Clin Chem, D-40225 Dusseldorf, Germany.
[Sobek, Stefan; Bornholz, Beatrice; Kalfalah, Faiza; Mielke, Christian; Christensen, Morten O.; Boege, Fritz] Univ Dusseldorf, Fac Med, Diagnost Lab, D-40225 Dusseldorf, Germany.
[Dalla Rosa, Ilaria; Pommier, Yves; Zhang, Hongliang] NCI, Natl Inst Hlth, Ctr Canc Res, Mol Pharmacol Lab, Bethesda, MD 20892 USA.
[Wiesner, Rudolf J.] Univ Cologne, Ctr Physiol & Pathophysiol, Inst Vegetat Physiol, D-50931 Cologne, Germany.
[Wiesner, Rudolf J.; von Kleist-Retzow, Juergen-Christoph] Univ Cologne, Ctr Mol Med Cologne, D-50931 Cologne, Germany.
[Wiesner, Rudolf J.] Univ Cologne, Cologne Excellence Cluster Cellular Stress Respon, D-50931 Cologne, Germany.
[von Kleist-Retzow, Juergen-Christoph] Univ Cologne, Fac Med, Dept Pediat, D-50931 Cologne, Germany.
[Hillebrand, Frank; Schaal, Heiner] Univ Dusseldorf, Fac Med, Ctr Microbiol & Virol, Inst Virol, D-40225 Dusseldorf, Germany.
RP Boege, F (reprint author), Univ Dusseldorf, Fac Med, Inst Clin Chem, D-40225 Dusseldorf, Germany.
EM boege@med.uni-duesseldorf.de
FU Deutsche Forschungsgemeinschaft [SFB 728, GRK 1033, DFG Wi 889/6-2];
National Institutes of Health, National Cancer Institute, Center for
Cancer Research
FX Deutsche Forschungsgemeinschaft [SFB 728 and GRK 1033 to F. B., DFG Wi
889/6-2 to R.J.W.] and the National Institutes of Health, National
Cancer Institute, Center for Cancer Research [Intramural Research
Program to Y.P.]. Funding for open access charge: Research budget of the
Institute of Clin. Chemistry and Lab. Diagnostics, Univ. Dusseldorf, of
which the corresponding author is the director.
NR 44
TC 11
Z9 11
U1 2
U2 16
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 NOV
PY 2013
VL 41
IS 21
BP 9848
EP 9857
DI 10.1093/nar/gkt768
PG 10
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 259QQ
UT WOS:000327541800027
PM 23982517
ER
PT J
AU Sugiman-Marangos, SN
Peel, JK
Weiss, YM
Ghirlando, R
Junop, MS
AF Sugiman-Marangos, Seiji N.
Peel, John K.
Weiss, Yoni M.
Ghirlando, Rodolfo
Junop, Murray S.
TI Crystal structure of the DdrB/ssDNA complex from Deinococcus radiodurans
reveals a DNA binding surface involving higher-order oligomeric states
SO NUCLEIC ACIDS RESEARCH
LA English
DT Article
ID ANALYTICAL ULTRACENTRIFUGATION; SEDIMENTATION-VELOCITY;
IONIZING-RADIATION; DDRB PROTEIN; REPAIR; RADIORESISTANCE; RESISTANCE;
DOMAIN; FORM
AB The ability of Deinococcus radiodurans to recover from extensive DNA damage is due in part to its ability to efficiently repair its genome, even following severe fragmentation by hundreds of double-strand breaks. The single-strand annealing pathway plays an important role early during the recovery process, making use of a protein, DdrB, shown to greatly stimulate ssDNA annealing. Here, we report the structure of DdrB bound to ssDNA to 2.3 A. Pentameric DdrB was found to assemble into higher-order structures that coat ssDNA. To gain further mechanistic insight into the protein's function, a number of point mutants were generated altering both DNA binding and higher order oligomerization. This work not only identifies higher-order DdrB associations but also suggests the presence of an extended DNA binding surface running along the 'top' surface of a DdrB pentamer and continuing down between two individual subunits of the ring structure. Together this work sheds new insight into possible mechanisms for DdrB function in which higher-order assemblies of DdrB pentamers assist in the pairing of complementary ssDNA using an extended DNA binding surface.
C1 [Sugiman-Marangos, Seiji N.; Peel, John K.; Weiss, Yoni M.; Junop, Murray S.] McMaster Univ, Dept Biochem & Biomed Sci, Hamilton, ON L8N 3Z5, Canada.
[Sugiman-Marangos, Seiji N.; Peel, John K.; Weiss, Yoni M.; Junop, Murray S.] McMaster Univ, MG DeGroote Inst Infect Dis Res, Hamilton, ON L8N 3Z5, Canada.
[Ghirlando, Rodolfo] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Junop, MS (reprint author), McMaster Univ, Dept Biochem & Biomed Sci, 1200 Main St W, Hamilton, ON L8N 3Z5, Canada.
EM junopm@mcmaster.ca
RI Junop, Murray/E-4160-2015
OI Junop, Murray/0000-0001-6676-5717
FU Natural Sciences and Engineering Research Council of Canada
[2008R00075]; Offices of Biological and Environmental Research and Basic
Energy Sciences of the US Department of Energy; National Center for
Research Resources [P41RR012408]; National Institute of General Medical
Sciences of the National Institutes of Health; Intramural Research
Program of the National Institutes Health [P41GM103473]; National
Institute of Diabetes and Digestive and Kidney Diseases, NIDDK; National
Science and Engineering Research Council of Canada
FX Natural Sciences and Engineering Research Council of Canada through
grant [2008R00075 to M.S.J.] and studentship (to S.N.S.M. and Y.M.W.);
Offices of Biological and Environmental Research and Basic Energy
Sciences of the US Department of Energy; National Center for Research
Resources [P41RR012408] and National Institute of General Medical
Sciences [P41GM103473] of the National Institutes of Health; Intramural
Research Program of the National Institutes Health, the National
Institute of Diabetes and Digestive and Kidney Diseases, NIDDK (in part)
(to R.G.). Funding for open access charge: National Science and
Engineering Research Council of Canada.
NR 32
TC 6
Z9 8
U1 0
U2 3
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0305-1048
EI 1362-4962
J9 NUCLEIC ACIDS RES
JI Nucleic Acids Res.
PD NOV
PY 2013
VL 41
IS 21
BP 9934
EP 9944
DI 10.1093/nar/gkt759
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 259QQ
UT WOS:000327541800035
PM 23975200
ER
PT J
AU Marcum, ZA
Zheng, Y
Perera, S
Strotmeyer, E
Newman, AB
Simonsick, EM
Shorr, RI
Bauer, DC
Donohue, JM
Hanlon, JT
AF Marcum, Zachary A.
Zheng, Yan
Perera, Subashan
Strotmeyer, Elsa
Newman, Anne B.
Simonsick, Eleanor M.
Shorr, Ronald I.
Bauer, Douglas C.
Donohue, Julie M.
Hanlon, Joseph T.
CA Hlth ABC Study
TI Prevalence and correlates of self-reported medication non-adherence
among older adults with coronary heart disease, diabetes mellitus,
and/or hypertension
SO RESEARCH IN SOCIAL & ADMINISTRATIVE PHARMACY
LA English
DT Article
DE Medication adherence; Chronic disease; Aged
ID CONCEPTUALLY BASED APPROACH; COST-RELATED NONADHERENCE;
BODY-COMPOSITION; RACIAL-DIFFERENCES; LOGISTIC-REGRESSION;
BLOOD-PRESSURE; HEALTH-CARE; PART-D; ADHERENCE; OUTCOMES
AB Background: Information about the prevalence and correlates of self-reported medication nonadherence using multiple measures in older adults with chronic cardiovascular conditions is needed.
Objective: To examine the prevalence and correlates of self-reported medication nonadherence among community-dwelling elders with chronic cardiovascular conditions.
Methods: Participants (n = 897) included members from the Health, Aging and Body Composition Study with coronary heart disease, diabetes mellitus, and/or hypertension at Year 10. Self-reported nonadherence was measured by the 4-item Morisky Medication Adherence Scale (MMAS-4) and 2-item cost-related nonadherence (CRN-2) scale at Year 11. Factors (demographic, health status, and access to care) were examined for association with the MMAS-4 and then for association with the CRN-2 scale.
Results: Nonadherence per the MMAS-4 and CRN-2 scale was reported by 40.7% and 7.7% of participants, respectively, with little overlap (3.7%). Multivariable logistic regression analyses found that black race was significantly associated with nonadherence per the MMAS-4 (P = 0.002) and the CRN-2 scale (P = 0.005). Other correlates of nonadherence per the MMAS-4 (with independent associations) included having cancer (P = 0.04), a history of falls (P = 0.02), sleep disturbances (P = 0.04) and having a hospitalization in the previous 6 months (P = 0.005). Conversely, being unmarried (P = 0.049), having worse self-reported health (P = 0.04) and needs being poorly met by income (P = 0.02) showed significant independent associations with nonadherence per the CRN-2 scale.
Conclusions: Self-reported medication nonadherence was common in older adults with chronic cardiovascular conditions and only one factor - race - was associated with both types. The research implication of this finding is that it highlights the need to measure both types of self-reported nonadherence in older adults. Moreover, the administration of these quick measures in the clinical setting should help identify specific actions such as patient education or greater use of generic medications or pill boxes that may address barriers to medication nonadherence. (C) 2013 Elsevier Inc. All rights reserved.
C1 [Marcum, Zachary A.; Zheng, Yan; Perera, Subashan; Newman, Anne B.; Hanlon, Joseph T.] Univ Pittsburgh, Sch Med, Dept Geriatr Med, Pittsburgh, PA 15213 USA.
[Perera, Subashan; Strotmeyer, Elsa; Newman, Anne B.; Hanlon, Joseph T.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA.
[Simonsick, Eleanor M.] NIA, Intramural Res Program, Baltimore, MD 21224 USA.
[Shorr, Ronald I.] Vet Affairs Med Ctr, Geriatr Res Educ & Clin Ctr, Gainesville, FL 32608 USA.
[Bauer, Douglas C.] Univ Calif San Francisco, Dept Med Gen Internal Med, San Francisco, CA 94143 USA.
[Donohue, Julie M.] Univ Pittsburgh, Dept Hlth Policy & Management, Pittsburgh, PA USA.
RP Marcum, ZA (reprint author), Univ Pittsburgh, Sch Med, Dept Geriatr Med, Pittsburgh, PA 15213 USA.
EM zam12@pitt.edu
RI Perera, Subashan/D-7603-2014; Strotmeyer, Elsa/F-3015-2014; Newman,
Anne/C-6408-2013;
OI Strotmeyer, Elsa/0000-0002-4093-6036; Newman, Anne/0000-0002-0106-1150;
Donohue, Julie/0000-0003-2418-6017
FU AHRQ HHS [K12 HS019461, R01 HS017695, R01 HS018721, R01HS018721]; NCATS
NIH HHS [KL2 TR000146, UL1 TR000005]; NIA NIH HHS [N01-AG-6-2101, K07
AG033174, K07-AG-033174, N01 AG062101, N01-AG-6-2103, N01-AG-6-2106, P30
AG024827, P30-AG-024827, R01 AG027017, R01 AG028050, R01 AG034056,
R01-AG-28050, R01AG034056, R56 AG027017, R56AG 027017]; NINR NIH HHS
[R01 NR010135, R01 NR012459, R01-NR12459]
NR 48
TC 21
Z9 21
U1 3
U2 18
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1551-7411
EI 1934-8150
J9 RES SOC ADMIN PHARM
JI Res. Soc. Adm. Pharm.
PD NOV-DEC
PY 2013
VL 9
IS 6
BP 817
EP 827
DI 10.1016/j.sapharm.2012.12.002
PG 11
WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy
SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy
GA 255PN
UT WOS:000327252400016
PM 23291338
ER
PT J
AU Magill, SS
Klompas, M
Balk, R
Burns, SM
Deutschman, CS
Diekema, D
Friclkin, S
Greene, L
Guh, A
Gutterman, D
Hammer, B
Henderson, D
Hess, DR
Hill, NS
Horan, T
Kollef, M
Levy, M
Septimus, E
Van Antwerpen, C
Wright, D
Lipsett, P
AF Magill, Shelley S.
Klompas, Michael
Balk, Robert
Burns, Suzanne M.
Deutschman, Clifford S.
Diekema, Daniel
Friclkin, Scott
Greene, Linda
Guh, Alice
Gutterman, David
Hammer, Beth
Henderson, David
Hess, Dean R.
Hill, Nicholas S.
Horan, Teresa
Kollef, Marin
Levy, Mitchell
Septimus, Edward
Van Antwerpen, Carole
Wright, Don
Lipsett, Pamela
TI Developing a New, National Approach to Surveillance for
Ventilator-Associated Events: Executive Summary
SO RESPIRATORY CARE
LA English
DT Article
DE ventilator-associated pneumonia; ICU; epidemiology; public health;
critical care; mechanicalventilation
C1 [Magill, Shelley S.; Friclkin, Scott; Guh, Alice; Horan, Teresa] Ctr Dis Control & Prevent, Div Healthcare Qual Promot, Atlanta, GA 30329 USA.
[Klompas, Michael] Harvard Univ, Sch Med, Dept Populat Med, Boston, MA USA.
[Klompas, Michael] Harvard Pilgrim Hlth Care Inst, Boston, MA USA.
[Klompas, Michael] Brigham & Womens Hosp, Infect Control Dept, Boston, MA 02115 USA.
[Klompas, Michael] Soc Healthcare Epidemiol Amer, Arlington, VA USA.
[Balk, Robert] Rush Univ, Sch Med, Div Pulm & Crit Care Med, Chicago, IL 60612 USA.
[Burns, Suzanne M.] Univ Virginia, Sch Nursing Crit & Acute Care, Charlottesville, VA USA.
[Deutschman, Clifford S.] Univ Penn, Perelman Sch Med, Dept Anesthesiol & Crit Care, Philadelphia, PA 19104 USA.
[Diekema, Daniel] Univ Iowa, Carver Coll Med, Div Infect Dis, Iowa City, IA USA.
[Diekema, Daniel] Healthcare Infect Control Practices Advisory Comm, Atlanta, GA USA.
[Greene, Linda] Rochester Gen Hlth Syst, Infect Prevent & Control Dept, Rochester, NY USA.
[Greene, Linda] Assoc Profess Infect Control & Epidemiol, Washington, DC USA.
[Gutterman, David] Med Coll Wisconsin, Dept Med, Milwaukee, WI 53226 USA.
[Hammer, Beth] Zablocki VA Med Ctr, Dept Cardiol, Milwaukee, WI USA.
[Henderson, David] NIH, Hosp Epidemiol & Qual Improvement, Ctr Clin, Bethesda, MD 20892 USA.
[Hess, Dean R.] Massachusetts Gen Hosp, Dept Resp Care, Boston, MA 02114 USA.
[Hess, Dean R.] Harvard Univ, Sch Med, Dept Anesthesia, Boston, MA 02115 USA.
[Hess, Dean R.] Amer Assoc Resp Care, Irving, TX USA.
[Hill, Nicholas S.] Tufts Med Ctr, Div Pulm & Crit Care Med, Boston, MA USA.
[Kollef, Marin] Washington Univ, Div Pulm & Crit Care Med, St Louis, MO USA.
[Levy, Mitchell] Brown Univ, Rhode Isl Hosp, Div Pulm Crit Care & Sleep, Warren Alpert Med Sch, Providence, RI 02903 USA.
[Septimus, Edward] Texas A&M Hlth Sci Ctr, Dept Internal Med, College Stn, TX USA.
[Septimus, Edward] Infect Dis Soc Amer, Arlington, VA USA.
[Van Antwerpen, Carole] New York State Dept Hlth, Dept Hlth, Bur Healthcare Associated Infect, Albany, NY USA.
[Van Antwerpen, Carole] Council State & Terr Epidemiologists, Atlanta, GA USA.
[Wright, Don] US Dept HHS, Off Dis Prevent & Hlth Promot, Washington, DC 20201 USA.
[Lipsett, Pamela] Johns Hopkins Univ, Sch Med, Dept Surg Anesthesiol & Crit Care Med, Baltimore, MD USA.
RP Magill, SS (reprint author), Ctr Dis Control & Prevent, Div Healthcare Qual Promot, 1600 Clifton Rd,MS A-24, Atlanta, GA 30329 USA.
EM smagill@cdc.gov
FU Centers for Disease Control and Prevention (CDC)
FX The work described herein was supported by the Centers for Disease
Control and Prevention (CDC).
NR 2
TC 2
Z9 2
U1 0
U2 2
PU DAEDALUS ENTERPRISES INC
PI IRVING
PA 9425 N MAC ARTHUR BLVD, STE 100, IRVING, TX 75063-4706 USA
SN 0020-1324
EI 1943-3654
J9 RESP CARE
JI Respir. Care
PD NOV
PY 2013
VL 58
IS 11
BP 1985
EP 1989
DI 10.4187/respcare.02759
PG 5
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA 252JZ
UT WOS:000327002300021
ER
PT J
AU Sanchez, GAM
de Jesus, AA
Goldbach-Mansky, R
AF Sanchez, Gina A. Montealegre
de Jesus, Adriana Almeida
Goldbach-Mansky, Raphaela
TI Monogenic Autoinflammatory Diseases: Disorders of Amplified Danger
Sensing and Cytokine Dysregulation
SO RHEUMATIC DISEASE CLINICS OF NORTH AMERICA
LA English
DT Article
DE Cryopyrin-associated periodic syndrome (CAPS); Neonatal-onset
multisystem inflammatory disease (NOMID); Proteasome-associated
autoinflammatory syndrome (PRAAS); Chronic atypical neutrophilic
dermatosis with lipodystrophy and elevated temperature (CANDLE);
Deficiency of the IL-1 receptor antagonist (DIRA); Inflammasome;
Autoinflammatory diseases; Intracellular pattern recognition receptors
(PRR)
ID FAMILIAL MEDITERRANEAN FEVER; MEVALONATE KINASE-DEFICIENCY;
MUCKLE-WELLS-SYNDROME; CONGENITAL DYSERYTHROPOIETIC ANEMIA; RECURRENT
MULTIFOCAL OSTEOMYELITIS; PEDIATRIC GRANULOMATOUS ARTHRITIS; GENERALIZED
PUSTULAR PSORIASIS; RILONACEPT INTERLEUKIN-1 TRAP;
INFLAMMATORY-BOWEL-DISEASE; PERIODIC SYNDROME TRAPS
AB The pathogenesis of monogenic autoinflammatory diseases converges on the presence of exaggerated immune responses that are triggered through activation of altered pattern recognition receptor (PRR) pathways and result in cytokine/chemokine amplification loops and the inflammatory clinical phenotype seen in autoinflammatory patients. The PAR response can be triggered by accumulation of metabolites, by mutations in sensors leading to their constitutive overactivation, or by mutations in mediator cytokine pathways that lead to amplification and/or inability to downregulate an inflammatory response in hematopoietic and/or nonhematopoietic cells. The study of the pathogenesis of sterile inflammation in patients with autoinflammatory syndromes continues to uncover novel inflammatory pathways.
C1 [Sanchez, Gina A. Montealegre; de Jesus, Adriana Almeida; Goldbach-Mansky, Raphaela] Natl Inst Arthrit & Musculoskeletal & Skin Dis NI, Translat Autoinflammatory Dis Sect, NIH, Bethesda, MD 20892 USA.
RP Goldbach-Mansky, R (reprint author), Natl Inst Arthrit & Musculoskeletal & Skin Dis NI, Translat Autoinflammatory Dis Sect, NIH, Bldg 10,Room 6D47-B,10 Ctr Dr, Bethesda, MD 20892 USA.
EM goldbacr@mail.nih.gov
FU Intramural NIH HHS [ZIA AR041138-07, Z01 AR041138-05, Z01 AR041138-06,
Z99 AR999999, ZIA AR041138-08, ZIA AR041138-09, ZIA AR041138-10]
NR 129
TC 15
Z9 16
U1 1
U2 7
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0889-857X
EI 1558-3163
J9 RHEUM DIS CLIN N AM
JI Rheum. Dis. Clin. North Am.
PD NOV
PY 2013
VL 39
IS 4
BP 701
EP +
DI 10.1016/j.rdc.2013.08.001
PG 35
WC Rheumatology
SC Rheumatology
GA 260BT
UT WOS:000327570700004
PM 24182851
ER
PT J
AU Ramanathan, A
Srinivasalu, H
Colbert, RA
AF Ramanathan, Anusha
Srinivasalu, Hemalatha
Colbert, Robert A.
TI Update on Juvenile Spondyloarthritis
SO RHEUMATIC DISEASE CLINICS OF NORTH AMERICA
LA English
DT Article
DE Juvenile spondyloarthritis; Enthesitis-related arthritis; Juvenile
psoriatic arthritis; HLA-B27; Axial spondyloarthritis
ID ENTHESITIS-RELATED ARTHRITIS; ACTIVE ANKYLOSING-SPONDYLITIS; DISTAL
INTERPHALANGEAL JOINT; ANTITUMOR NECROSIS FACTOR; SOCIETY CLASSIFICATION
CRITERIA; UNFOLDED PROTEIN RESPONSE; MAJOR CLINICAL-RESPONSE; IDIOPATHIC
ARTHRITIS; PSORIATIC-ARTHRITIS; RADIOGRAPHIC PROGRESSION
AB Spondyloarthritis (SpA) encompasses a group of disorders linked by overlapping clinical manifestations and genetic predisposition. Newer classification systems developed for adults with SpA focus on identifying individuals with axial or predominantly peripheral involvement. All forms of SpA can begin during childhood, and can be considered on a continuum with adult disease. Nevertheless, there are important differences in presentation and outcome that depend on age at onset. This article highlights these differences, what has been learned about genetics and pathogenesis of SpA, and important unmet needs for future studies.
C1 [Ramanathan, Anusha] Childrens Hosp Los Angeles, Keck Sch Med USC, Div Rheumatol, Los Angeles, CA 90027 USA.
[Srinivasalu, Hemalatha] George Washington Univ, Childrens Natl Med Ctr, Div Rheumatol, Washington, DC 20010 USA.
[Colbert, Robert A.] Natl Inst Arthrit Musculoskeletal & Skin Dis NIAM, Pediat Translat Res Branch, NIH, Bethesda, MD 20892 USA.
RP Colbert, RA (reprint author), Natl Inst Arthrit Musculoskeletal & Skin Dis NIAM, Pediat Translat Res Branch, NIH, Bldg 10 CRC Rm 1-5142,10 Ctr Dr, Bethesda, MD 20892 USA.
EM colbertr@mail.nih.gov
FU NIAMS Intramural Research Program [Z01 AR041184]
FX R.A. Colbert was supported by the NIAMS Intramural Research Program, Z01
AR041184.
NR 103
TC 6
Z9 7
U1 1
U2 3
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0889-857X
EI 1558-3163
J9 RHEUM DIS CLIN N AM
JI Rheum. Dis. Clin. North Am.
PD NOV
PY 2013
VL 39
IS 4
BP 767
EP +
DI 10.1016/j.rdc.2013.06.002
PG 23
WC Rheumatology
SC Rheumatology
GA 260BT
UT WOS:000327570700007
PM 24182854
ER
PT J
AU Rider, LG
Katz, JD
Jones, OY
AF Rider, Lisa G.
Katz, James D.
Jones, Olcay Y.
TI Developments in the Classification and Treatment of the Juvenile
Idiopathic Inflammatory Myopathies
SO RHEUMATIC DISEASE CLINICS OF NORTH AMERICA
LA English
DT Article
DE Juvenile myositis; Juvenile dermatomyositis; Juvenile polymyositis;
Overlap myositis; Myositis-specific autoantibodies; Treatment; Biologic
therapies
ID CLINICALLY AMYOPATHIC DERMATOMYOSITIS; INCLUSION-BODY MYOSITIS; ALLIANCE
CONSENSUS CONFERENCE; CONNECTIVE-TISSUE DISEASES; INTERSTITIAL
LUNG-DISEASE; NECROSIS-FACTOR-ALPHA; GENE 5 ANTIBODY; MACROPHAGIC
MYOFASCIITIS; ORBITAL MYOSITIS; INTRAVENOUS CYCLOPHOSPHAMIDE
AB This review updates recent trends in the classification of the juvenile idiopathic inflammatory myopathies (JIIM) and the emerging standard of treatment of the most common form of JIIM, juvenile dermatomyositis. The JIIM are rare, heterogeneous autoimmune diseases that share chronic muscle inflammation and weakness. A growing spectrum of clinicopathologic groups and serologic phenotypes defined by the presence of myositis autoantibodies are now recognized, each with differing demographics, clinical manifestations, laboratory findings, and prognoses. Although daily oral corticosteroids remain the backbone of treatment, disease-modifying anti-rheumatic drugs are almost always used adjunctively and biologic therapies may benefit patients with recalcitrant disease.
C1 [Rider, Lisa G.] Natl Inst Environm Hlth Sci, Environm Autoimmun Grp, Program Clin Res, NIH, Bethesda, MD 20892 USA.
[Rider, Lisa G.; Katz, James D.; Jones, Olcay Y.] George Washington Univ, Dept Med, Myositis Ctr, Div Rheumatol, Washington, DC 20037 USA.
[Jones, Olcay Y.] Walter Reed Natl Mil Med Ctr, Div Pediat Rheumatol, Dept Pediat, Bethesda, MD 20889 USA.
RP Rider, LG (reprint author), Natl Inst Environm Hlth Sci, Environm Autoimmun Grp, Program Clin Res, NIH, CRC 4-2352,MSC 1301,10 Ctr Dr, Bethesda, MD 20892 USA.
EM riderl@mail.nih.gov
RI hui, li/L-5008-2013;
OI Rider, Lisa/0000-0002-6912-2458
FU Intramural Research Program of the NIH, National Institute of
Environmental Health
FX This research was supported in part by the Intramural Research Program
of the NIH, National Institute of Environmental Health. The authors have
no conflicts of interest.
NR 138
TC 18
Z9 19
U1 2
U2 10
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0889-857X
EI 1558-3163
J9 RHEUM DIS CLIN N AM
JI Rheum. Dis. Clin. North Am.
PD NOV
PY 2013
VL 39
IS 4
BP 877
EP +
DI 10.1016/j.rdc.2013.06.001
PG 29
WC Rheumatology
SC Rheumatology
GA 260BT
UT WOS:000327570700012
PM 24182859
ER
PT J
AU Burks, SR
Ziadloo, A
Kim, SJ
Nguyen, BA
Frank, JA
AF Burks, Scott R.
Ziadloo, Ali
Kim, Saejeong J.
Nguyen, Ben A.
Frank, Joseph A.
TI Noninvasive Pulsed Focused Ultrasound Allows Spatiotemporal Control of
Targeted Homing for Multiple Stem Cell Types in Murine Skeletal Muscle
and the Magnitude of Cell Homing Can Be Increased Through Repeated
Applications
SO STEM CELLS
LA English
DT Article
DE Pulsed focused ultrasound; High intensity focused ultrasound; Stem
cells; Mesenchymal stem cells; Endothelial precursor cells; Targeted
delivery
ID MARROW STROMAL CELLS; BONE-MARROW; CEREBRAL-ISCHEMIA; IN-VIVO;
MICROBUBBLE DESTRUCTION; MYOCARDIAL-INFARCTION; PROGENITOR CELLS;
SATELLITE CELLS; ADIPOSE-TISSUE; SOLID TUMORS
AB Stem cells are promising therapeutics for cardiovascular diseases, and i.v. injection is the most desirable route of administration clinically. Subsequent homing of exogenous stem cells to pathological loci is frequently required for therapeutic efficacy and is mediated by chemoattractants (cell adhesion molecules, cytokines, and growth factors). Homing processes are inefficient and depend on short-lived pathological inflammation that limits the window of opportunity for cell injections. Noninvasive pulsed focused ultrasound (pFUS), which emphasizes mechanical ultrasound-tissue interactions, can be precisely targeted in the body and is a promising approach to target and maximize stem cell delivery by stimulating chemoattractant expression in pFUS-treated tissue prior to cell infusions. We demonstrate that pFUS is nondestructive to murine skeletal muscle tissue (no necrosis, hemorrhage, or muscle stem cell activation) and initiates a largely M2-type macrophage response. We also demonstrate that local upregulation of chemoattractants in pFUS-treated skeletal muscle leads to enhance homing, permeability, and retention of human mesenchymal stem cells (MSC) and human endothelial precursor cells (EPC). Furthermore, the magnitude of MSC or EPC homing was increased when pFUS treatments and cell infusions were repeated daily. This study demonstrates that pFUS defines transient molecular zip codes of elevated chemoattractants in targeted muscle tissue, which effectively provides spatiotemporal control and tunability of the homing process for multiple stem cell types. pFUS is a clinically translatable modality that may ultimately improve homing efficiency and flexibility of cell therapies for cardiovascular diseases. Stem Cells2013;31:2551-2560
C1 [Burks, Scott R.; Ziadloo, Ali; Kim, Saejeong J.; Nguyen, Ben A.; Frank, Joseph A.] NIH, Frank Lab, Ctr Clin, Bethesda, MD 20892 USA.
[Burks, Scott R.] NIH, Imaging Sci Training Program, Ctr Clin, Bethesda, MD 20892 USA.
Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD USA.
[Frank, Joseph A.] Natl Inst Biomed Imaging & Bioengn, Intramural Res Program, Bethesda, MD USA.
RP Burks, SR (reprint author), 10 Ctr Dr,Room B1N256, Bethesda, MD 20892 USA.
EM scott.burks@nih.gov
FU Intramural Research Program of the NIH Clinical Center; National
Institute of Biomedical Imaging and Bioengineering
FX This research was funded by the Intramural Research Program of the NIH
Clinical Center and National Institute of Biomedical Imaging and
Bioengineering.
NR 49
TC 10
Z9 11
U1 0
U2 9
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 2013
VL 31
IS 11
BP 2551
EP 2560
DI 10.1002/stem.1495
PG 10
WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology;
Oncology; Cell Biology; Hematology
SC Cell Biology; Biotechnology & Applied Microbiology; Oncology; Hematology
GA 252QY
UT WOS:000327025600024
PM 23922277
ER
PT J
AU Albanese, E
Taylor, C
Siervo, M
Stewart, R
Prince, MJ
Acosta, D
AF Albanese, Emiliano
Taylor, Clare
Siervo, Mario
Stewart, Robert
Prince, Martin J.
Acosta, Daisy
TI Dementia severity and weight loss: A comparison across eight cohorts.
The 10/66 study
SO ALZHEIMERS & DEMENTIA
LA English
DT Article
DE Dementia; Dementia severity; Weight loss; Developing countries;
Epidemiology; Observational study; Older adults; Population-based
sample; Cross-cohort; Meta-analysis; Aging
ID BODY-MASS INDEX; CROSS-SECTIONAL SURVEYS; ALZHEIMERS-DISEASE; INCIDENT
DEMENTIA; LATIN-AMERICA; MORTALITY; ASSOCIATION; COMMUNITY;
METAANALYSIS; PREVALENCE
AB Background: We aimed to investigate the association between dementia severity and weight loss in countries with low and middle incomes, where most prevalent cases reside.
Methods: Cross-sectional catchment area surveys were performed in Cuba, Mexico, Venezuela, Peru, Dominican Republic, Puerto Rico, China, and India. In 16,538 older adults (>= 65 years of age), significant weight loss was self-reported and confirmed by an informant. We conducted neuropsychological testing and clinical and neurological assessments. Dementia severity was determined by applying a validated algorithm and was quantified by the Clinical Dementia Rating Scale.
Results: The characteristics of those who reported weight loss varied across countries. In Poisson models, after controlling for relevant covariates and for waist and arm circumferences, dementia severity was associated with reported weight loss (pooled prevalence ratios [95% confidence intervals {CI]] 2.19 [1.98, 2.41]; 3.81 [3.35,4.33]; and 5.18 [4.41, 6.10] for CDR 0.5, 1, and 2/3, respectively, compared with CDR 0). The association increased linearly through stages of dementia severity in all countries (P for trend < .001), and between-country heterogeneity was minimal.
Conclusions: We found a strong gradient effect in the direct association between dementia severity and reported weight loss, homogeneous across sites from eight countries, consistent with mechanistic data on the role of neurodegenerative processes on energy balance and with dietary changes due to disease severity. Considering the well-recognized effect of weight loss on morbidity and mortality and the large number affected by dementia in less resourced countries, amelioration of weight loss in dementia patients should be considered with priority in these settings. (C) 2013 The Alzheimer's Association. All rights reserved.
C1 [Albanese, Emiliano] NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD 20892 USA.
[Taylor, Clare; Stewart, Robert; Prince, Martin J.] Kings Coll London, Inst Psychiat, London WC2R 2LS, England.
[Siervo, Mario] Newcastle Univ, Inst Ageing & Hlth, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England.
[Acosta, Daisy] Univ Nacl Pedro Henriquez Urena, Dept Internal Med, Santo Domingo, Dominican Rep.
RP Albanese, E (reprint author), NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD 20892 USA.
EM emiliano.albanese@gmail.com
RI Prince, Martin/A-9170-2010;
OI Prince, Martin/0000-0003-1379-7146; Stewart, Robert/0000-0002-4435-6397
FU Wellcome Trust (UK) [GR066133]; World Health Organization; U.S.
Alzheimer's Association [IIRG-04-1286]; FondoNacional de Ciencia Y
Tecnologia, Consejo de DesarolloCientifico Y Humanistic, Universidad
Central de Venezuela (Venezuela); GlaxoSmithKline; Novartis; Lundbeck;
Pfizer; Eisai; National Institute on Aging; National Institutes of
Health; National Institute for Health Research (NIHR) Biomedical
Research Centre; Dementia Biomedical Research Unit at South London;
Maudsley NHS Foundation Trust; King's College London
FX The 10/66 Dementia Research Group population-based surveys were funded
by the Wellcome Trust (UK) (GR066133); the World Health Organization;
the U.S. Alzheimer's Association (IIRG-04-1286); and the FondoNacional
de Ciencia Y Tecnologia, Consejo de DesarolloCientifico Y Humanistic,
Universidad Central de Venezuela (Venezuela). The Rockefeller Foundation
supported a dissemination meeting in their Bellagio Centre. Alzheimer's
Disease International (ADI) has provided support for networking and
infrastructure. The 10/66 Dementia Research Group works closely with
ADI, which is a nonprofit federation of 77 Alzheimer associations around
the world. ADI is committed to strengthening Alzheimer associations
worldwide, raising awareness regarding dementia and Alzheimer's disease,
and advocating for more and better services for people with dementia and
their caregivers. ADI is supported in part by grants from
GlaxoSmithKline, Novartis, Lundbeck, Pfizer, and Eisai. Emiliano
Albanese is supported by the Intramural Research Program of the National
Institute on Aging and the National Institutes of Health. Robert Stewart
is partly funded by the National Institute for Health Research (NIHR)
Biomedical Research Centre, the Dementia Biomedical Research Unit at
South London, the Maudsley NHS Foundation Trust, and King's College
London. None of the funders had any role in the design, data collection,
manuscript writing, or decision to submit for publication.
NR 40
TC 16
Z9 16
U1 1
U2 10
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1552-5260
EI 1552-5279
J9 ALZHEIMERS DEMENT
JI Alzheimers. Dement.
PD NOV
PY 2013
VL 9
IS 6
BP 649
EP 656
DI 10.1016/j.jalz.2012.11.014
PG 8
WC Clinical Neurology
SC Neurosciences & Neurology
GA 254NP
UT WOS:000327172700005
PM 23474042
ER
PT J
AU Breitner, J
Baker, L
Drye, L
Evans, D
Lyketsos, C
Ryan, L
Zandi, P
Baker, L
Breitner, J
Saucedo, HH
Anau, J
Cholerton, B
Kramer, K
Zandi, P
Drye, L
Casper, AS
Meinert, C
Martin, B
Jenkins, G
McCaffrey, L
Meinert, J
Vaidya, V
Ahuja, A
May, P
Ryan, L
Lyketsos, CG
Steinberg, M
Brandt, J
Pedroso, JJ
Bergey, A
Gogel, C
Smith, L
Kraus, J
Stern, RA
Green, RC
Gavett, B
Mwicigi, J
Baldwin, L
McGowan, T
Johnson, P
Qiu, W
Frederick, J
Raghavan, S
Rossi, C
Mandell, A
Dinizo, D
Roth, MT
Porsteinsson, A
Ismail, MS
Weber, M
Brand, C
Richard, J
Stear, K
Schepp, S
Cosman, K
Martin, K
Craft, S
Baker, L
Dahl, D
Garrett, G
Tidwell, J
Thielke, S
Smith, L
Arbuckle, M
Strong, W
Ladenberg, J
Callaghan, M
Watson, S
Skinner, J
Bowton, K
Sabbagh, M
Belden, C
Liebsack, C
Davis, K
Arnieri, L
Malek-Ahmadi, M
Nicholson, L
Jacobson, S
Schwartz, E
Mullan, M
Luis, C
Parrish, J
Faircloth, M
Ervin, T
Girard, J
Burke, D
Keegan, A
Evans, D
AF Breitner, John
Baker, Laura
Drye, Lea
Evans, Denis
Lyketsos, Constantine
Ryan, Laurie
Zandi, Peter
Baker, Laura
Breitner, John
Saucedo, Hector Hernandez
Anau, Jane
Cholerton, Brenna
Kramer, Kirise
Zandi, Peter
Drye, Lea
Casper, Anne Shanklin
Meinert, Curtis
Martin, Barbara
Jenkins, Gabrielle
McCaffrey, Lee
Meinert, Jill
Vaidya, Vijay
Ahuja, Alka
May, Pat
Ryan, Laurie
Lyketsos, Constantine G.
Steinberg, Martin
Brandt, Jason
Pedroso, Julia J.
Bergey, Alyssa
Gogel, Carol
Smith, Lynn
Kraus, Jennifer
Stern, Robert A.
Green, Robert C.
Gavett, Brandon
Mwicigi, Jane
Baldwin, Lorraine
McGowan, Theresa
Johnson, Patricia
Qiu, Wendy
Frederick, Jamie
Raghavan, Sumati
Rossi, Carol
Mandell, Alan
Dinizo, Daniella
Roth, Mary Tara
Porsteinsson, Anton
Ismail, M. Saleem
Weber, Miriam
Brand, Connie
Richard, Jennifer
Stear, Kelly
Schepp, Sue
Cosman, Kelly
Martin, Kimberly
Craft, Suzanne
Baker, Laura
Dahl, Deborah
Garrett, Grace
Tidwell, Jamie
Thielke, Stephen
Smith, Lauren
Arbuckle, Matthew
Strong, William
Ladenberg, Juliet
Callaghan, Maureen
Watson, Stennis
Skinner, Jeannine
Bowton, Kaysha
Sabbagh, Marwan
Belden, Christine
Liebsack, Carolyn
Davis, Kathryn
Arnieri, Lauren
Malek-Ahmadi, Michael
Nicholson, Lisa
Jacobson, Sandra
Schwartz, Elliot
Mullan, Michael
Luis, Cheryl
Parrish, Julia
Faircloth, Marlee
Ervin, Terry
Girard, Janette
Burke, Deborah
Keegan, Andrew
Evans, Denis
CA Alzheimer's Dis Antiinflammatory
TI Results of a follow-up study to the randomized Alzheimer's Disease
Anti-inflammatory Prevention Trial (ADAPT) The Alzheimer's Disease
Anti-inflammatory Prevention Trial Research Group
SO ALZHEIMERS & DEMENTIA
LA English
DT Article
DE Prevention; Clinical trial; Alzheimer's disease; Nonsteroidal
anti-inflammatory drug; Naproxen; Celecoxib
ID DOUBLE-BLIND; DRUGS; ROFECOXIB; NAPROXEN; PLACEBO; INHIBITION;
CELECOXIB; ASPIRIN; DESIGN; NSAIDS
AB Objectives: The Alzheimer's Disease Anti-inflammatory Prevention Trial Follow-up Study (ADAPT-FS) was designed to evaluate the efficacy of naproxen and celecoxib for the primary prevention of Alzheimer's disease (AD) several years after cessation of treatment in ADAPT.
Methods: ADAPT was a randomized, double-masked, multicenter clinical trial of naproxen or celecoxib vs placebo (1:1:1.5 assignment ratio) at six U.S.-based clinics. The trial enrolled 2528 people between 2001 and 2004. Treatments were discontinued in December 2004 and participants were monitored regularly until 2007. In 2010 and 2011, ADAPT-FS screened 1537 participants by telephone and, if indicated, examined them in person using standardized clinical assessments. The primary outcome was time to diagnosis of AD. Death index searches were performed for participants not located.
Results: Eighty-nine additional AD events were identified (24 celecoxib, 25 naproxen, and 40 placebo) yielding a total of 161 events (48 [6.6% of randomized participants] celecoxib, 43 [6.0%] naproxen, and 70 [6.5%] placebo) across ADAPT and ADAPT-FS. Adjusted hazard ratios (HRs) comparing each treatment with placebo showed no overall reduction in risk of AD: HR celecoxib vs placebo, 1.03 (95% confidence interval [CI], 0.72-1.50; P = .86); HR naproxen vs placebo, 0.92 (95% CI, 0.62-1.35; P = .66). There were 349 deaths (110 [15.2%] celecoxib, 96 [13.4%] naproxen, and 143 [13.2%] placebo). Risk of death was similar for the naproxen- and placebo-assigned groups (HR, 0.99; 95% CI, 0.76-1.28; P = .93) and slightly higher for celecoxib compared with the placebo-assigned group (HR, 1.15; 95% CI, 0.90-1.48; P = .27).
Conclusions: These results acquired during a follow-up of approximately 7 years (which included a median of less than 1.5 years of treatment) do not support the hypothesis that celecoxib or naproxen prevent AD in adults with a family history of dementia. 2013 The Alzheimer's Association. All rights reserved.
C1 [Breitner, John; Baker, Laura; Breitner, John] Douglas Mental Hlth Univ Inst, Ctr Studies Prevent Alzheimers Dis, Montreal, PQ, Canada.
[Breitner, John; Baker, Laura; Breitner, John] McGill Univ, Montreal, PQ, Canada.
[Baker, Laura; Porsteinsson, Anton; Ismail, M. Saleem; Weber, Miriam; Brand, Connie; Richard, Jennifer; Stear, Kelly; Schepp, Sue; Cosman, Kelly; Martin, Kimberly] Veteran Affairs Puget Sound Hlth Care Syst, Seattle, WA USA.
[Baker, Laura; Zandi, Peter; Porsteinsson, Anton; Ismail, M. Saleem; Weber, Miriam; Brand, Connie; Richard, Jennifer; Stear, Kelly; Schepp, Sue; Cosman, Kelly; Martin, Kimberly] Univ Washington, Sch Med, Seattle, WA USA.
[Drye, Lea; Zandi, Peter; Saucedo, Hector Hernandez; Anau, Jane; Cholerton, Brenna; Kramer, Kirise] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Evans, Denis; Mullan, Michael; Luis, Cheryl; Parrish, Julia; Faircloth, Marlee; Ervin, Terry; Girard, Janette; Burke, Deborah; Keegan, Andrew; Evans, Denis] Rush Presbyterian St Lukes Med Ctr, Chicago, IL 60612 USA.
[Lyketsos, Constantine; Ryan, Laurie] Johns Hopkins Sch Med, Baltimore, MD 60612 USA.
[Ryan, Laurie] NIA, Bethesda, MD 20892 USA.
[Zandi, Peter] Vet Affairs Puget Sound Hlth Care Syst, Res Grp Resource Ctr Chairmans Off, Seattle, WA USA.
[Zandi, Peter; Drye, Lea; Casper, Anne Shanklin; Meinert, Curtis; Martin, Barbara; Jenkins, Gabrielle; McCaffrey, Lee; Meinert, Jill; Vaidya, Vijay; Ahuja, Alka; May, Pat] NIA, Project Off, Bethesda, MD 20892 USA.
[Lyketsos, Constantine G.; Steinberg, Martin; Brandt, Jason; Pedroso, Julia J.; Bergey, Alyssa; Gogel, Carol; Smith, Lynn; Kraus, Jennifer] Boston Univ, Sch Med, Boston, MA 02118 USA.
[Stern, Robert A.; Green, Robert C.; Gavett, Brandon; Mwicigi, Jane; Baldwin, Lorraine; McGowan, Theresa; Johnson, Patricia; Qiu, Wendy; Frederick, Jamie; Raghavan, Sumati; Rossi, Carol; Mandell, Alan; Dinizo, Daniella; Roth, Mary Tara] Univ Rochester, Sch Med, Rochester, NY USA.
[Craft, Suzanne; Baker, Laura; Dahl, Deborah; Garrett, Grace; Tidwell, Jamie; Thielke, Stephen; Smith, Lauren; Arbuckle, Matthew; Strong, William; Ladenberg, Juliet; Callaghan, Maureen; Watson, Stennis; Skinner, Jeannine; Bowton, Kaysha] Sun Hlth Res Inst, Sun City, AZ USA.
[Sabbagh, Marwan; Belden, Christine; Liebsack, Carolyn; Davis, Kathryn; Arnieri, Lauren; Malek-Ahmadi, Michael; Nicholson, Lisa; Jacobson, Sandra; Schwartz, Elliot] Roskamp Inst Memory Clin, Tampa, FL USA.
RP Breitner, J (reprint author), Douglas Mental Hlth Univ Inst, Ctr Studies Prevent Alzheimers Dis, Montreal, PQ, Canada.
EM ldrye@jhsph.edu
FU National Institute on Aging (NIA) [U01 AG15477, 2U01 AG015477-06A2]; N.
Bud Grossman Center for Memory Research and Care; Minnesota Medical
Foundation
FX Funding for this study was provided by the National Institute on Aging
(NIA) U01 AG15477 and 2U01 AG015477-06A2, the N. Bud Grossman Center for
Memory Research and Care, and the Minnesota Medical Foundation.
NR 28
TC 25
Z9 25
U1 1
U2 16
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1552-5260
EI 1552-5279
J9 ALZHEIMERS DEMENT
JI Alzheimers. Dement.
PD NOV
PY 2013
VL 9
IS 6
BP 714
EP 723
DI 10.1016/j.jalz.2012.11.012
PG 10
WC Clinical Neurology
SC Neurosciences & Neurology
GA 254NP
UT WOS:000327172700012
ER
PT J
AU McHugh, MJ
Demers, CH
Braud, J
Briggs, R
Adinoff, B
Stein, EA
AF McHugh, Meredith J.
Demers, Catherine H.
Braud, Jacquelyn
Briggs, Richard
Adinoff, Bryon
Stein, Elliot A.
TI Striatal-insula circuits in cocaine addiction: implications for
impulsivity and relapse risk
SO AMERICAN JOURNAL OF DRUG AND ALCOHOL ABUSE
LA English
DT Article
DE Addiction; cocaine; connectivity; impulsivity; insula; neuroimaging;
relapse; striatum
ID MEDIAL PREFRONTAL CORTEX; FUNCTIONAL CONNECTIVITY; NEURAL SYSTEMS;
DECISION-MAKING; DRUG-ADDICTION; DEPENDENT INDIVIDUALS; INDUCED
REINSTATEMENT; OUTCOME PREDICTORS; DOPAMINE-RECEPTORS; TRAIT IMPULSIVITY
AB Background: Dysregulated striatal functioning coupled with executive control deficits arising from abnormal frontal cortical function are considered key mechanisms in the development and maintenance of cocaine addiction. The same features are thought to underlie high trait impulsivity observed in cocaine-addicted populations. Objectives: Employing resting state functional connectivity, the current study sought to identify cortico-striatal circuit alterations in cocaine addiction and examine the degree to which circuit connectivity contributes to relapse risk and impulsivity among cocaine-addicted individuals. Methods: Whole-brain resting-state functional magnetic resonance imaging connectivity was assessed in 45 cocaine-addicted individuals relative to 22 healthy controls using seed volumes in the left and right caudate, putamen and nucleus accumbens. Cocaine-addicted individuals completed scans in the final week of a 2-4 weeks residential treatment episode. Relapse by day 30 post-discharge served to separate cocaine-addicted individuals into relapse and non-relapse groups. All participants completed the Barratt Impulsivity Scale (BIS-11a). Results: Cocaine-addicted individuals exhibited reduced positive connectivity between the bilateral putamen and posterior insula and right postcentral gyrus. Group differences were primarily driven by reduced connectivity in relapse individuals relative to controls. No relapse versus non-relapse differences emerged. Impulsivity (BIS-11a) was higher in cocaine-addicted participants, an effect that was partially mediated by reduced putamen-posterior insula connectivity in this group. Conclusion: Cocaine addiction, relapse risk and impulsivity were associated with reduced connectivity in putamen-posterior insula/postcentral gyrus circuits implicated in temporal discounting and habitual responding. Findings provide new insight into the neurobiological mechanisms underlying impulsivity and relapse in cocaine addiction.
C1 [McHugh, Meredith J.; Demers, Catherine H.; Stein, Elliot A.] NIDA, Neuroimaging Res Branch, Intramural Res Program, Baltimore, MD 21224 USA.
[Braud, Jacquelyn; Adinoff, Bryon] UT Southwestern Med Ctr, Dept Psychiat, Dallas, TX USA.
[Briggs, Richard] UT Southwestern Med Ctr, Dept Radiol, Dallas, TX USA.
[Adinoff, Bryon] VA North Texas Hlth Care Syst, Dallas, TX USA.
RP McHugh, MJ (reprint author), NIDA, Neuroimaging Res Branch, NIH, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM meredith.mchugh@nih.gov; EStein@intra.nida.nih.gov
FU Intramural NIH HHS; NIDA NIH HHS [DA023203]
NR 79
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Z9 30
U1 2
U2 21
PU TAYLOR & FRANCIS INC
PI PHILADELPHIA
PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA
SN 0095-2990
EI 1097-9891
J9 AM J DRUG ALCOHOL AB
JI Am. J. Drug Alcohol Abuse
PD NOV
PY 2013
VL 39
IS 6
SI SI
BP 424
EP 432
DI 10.3109/00952990.2013.847446
PG 9
WC Psychology, Clinical; Substance Abuse
SC Psychology; Substance Abuse
GA 251YE
UT WOS:000326969600011
PM 24200212
ER
PT J
AU Malekzadeh, MM
Khademi, H
Pourshams, A
Etemadi, A
Poustchi, H
Bagheri, M
Khoshnia, M
Sohrabpour, AA
Aliasgari, A
Jafari, E
Islami, F
Semnani, S
Abnet, CC
Pharoah, PDP
Brennan, P
Boffetta, P
Dawsey, SM
Malekzadeh, R
Kamangar, F
AF Malekzadeh, Masoud M.
Khademi, Hooman
Pourshams, Akram
Etemadi, Arash
Poustchi, Hossein
Bagheri, Mohammad
Khoshnia, Masoud
Sohrabpour, Amir Ali
Aliasgari, Ali
Jafari, Elham
Islami, Farhad
Semnani, Shahryar
Abnet, Christian C.
Pharoah, Paul D. P.
Brennan, Paul
Boffetta, Paolo
Dawsey, Sanford M.
Malekzadeh, Reza
Kamangar, Farin
TI Opium Use and Risk of Mortality from Digestive Diseases: A Prospective
Cohort Study
SO AMERICAN JOURNAL OF GASTROENTEROLOGY
LA English
DT Article
ID CORONARY-ARTERY-DISEASE; FATTY LIVER-DISEASE; ESOPHAGEAL CANCER;
GOLESTAN COHORT; BLADDER-CANCER; IRAN; ADDICTION; MORPHINE; OPIOIDS;
METABOLISM
AB OBJECTIVES: Opium use, particularly in low doses, is a common practice among adults in northeastern Iran. We aimed to investigate the association between opium use and subsequent mortality from disorders of the digestive tract.
METHODS: We used data from the Golestan Cohort Study, a prospective cohort study in northeastern Iran, with detailed, validated data on opium use and several other exposures. A total of 50,045 adults were enrolled during a 4-year period (2004-2008) and followed annually until December 2012, with a follow-up success rate of 99%. We used Cox proportional hazard regression models to evaluate the association between opium use and outcomes of interest.
RESULTS: In all, 8,487 (17%) participants reported opium use, with a mean duration of 12.7 years. During the follow-up period 474 deaths from digestive diseases were reported (387 due to gastrointestinal cancers and 87 due to nonmalignant etiologies). Opium use was associated with an increased risk of death from any digestive disease (adjusted hazard ratio (HR)=1.55, 95% confidence interval (CI)=1.24-1.93). The association was dose dependent, with a HR of 2.21 (1.57-3.31) for the highest quintile of cumulative opium use vs. no use (P-trend=0.037). The HRs (95% CI) for the associations between opium use and malignant and nonmalignant causes of digestive mortality were 1.38 (1.07-1.76) and 2.60 (1.57-4.31), respectively. Increased risks were seen both for smoking opium and for ingestion of opium.
CONCLUSIONS: Long-term opium use, even in low doses, is associated with increased risk of death from both malignant and nonmalignant digestive diseases.
C1 [Malekzadeh, Masoud M.; Khademi, Hooman; Pourshams, Akram; Etemadi, Arash; Poustchi, Hossein; Bagheri, Mohammad; Sohrabpour, Amir Ali; Aliasgari, Ali; Jafari, Elham; Islami, Farhad; Malekzadeh, Reza; Kamangar, Farin] Univ Tehran Med Sci, Shariati Hosp, Digest Dis Res Ctr, Tehran, Iran.
[Khademi, Hooman; Brennan, Paul] Int Agcy Res Canc, F-69372 Lyon, France.
[Etemadi, Arash; Abnet, Christian C.; Dawsey, Sanford M.; Kamangar, Farin] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Khoshnia, Masoud; Semnani, Shahryar] Golestan Univ Med Sci, GRCGH, Gorgan, Iran.
[Islami, Farhad] Mt Sinai Sch Med, Tisch Canc Inst, New York, NY USA.
[Islami, Farhad] Inst Translat Epidemiol, New York, NY USA.
[Pharoah, Paul D. P.; Boffetta, Paolo] Univ Cambridge, Dept Oncol, Cambridge, England.
[Pharoah, Paul D. P.; Boffetta, Paolo] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England.
[Boffetta, Paolo] Int Prevent Res Inst, Lyon, France.
[Kamangar, Farin] Morgan State Univ, Dept Publ Hlth Anal, Sch Community Hlth & Policy, Baltimore, MD 21251 USA.
RP Kamangar, F (reprint author), Morgan State Univ, Dept Publ Hlth Anal, Sch Community Hlth & Policy, Portage Ave Campus,Room 302, Baltimore, MD 21251 USA.
EM farin.kamangar@morgan.edu
RI Abnet, Christian/C-4111-2015; Etemadi, Arash/C-1386-2016; Semnani,
Shahryar/N-2270-2016; Khoshnia, Masoud/P-5665-2016;
OI Abnet, Christian/0000-0002-3008-7843; Etemadi,
Arash/0000-0002-3458-1072; Semnani, Shahryar/0000-0002-8768-6142;
Khoshnia, Masoud/0000-0001-7352-8058; Malekzadeh,
Reza/0000-0003-1043-3814
FU Tehran University of Medical Sciences [81/15]; Cancer Research UK
[C20/A5860]; Intramural Research Program of the National Cancer
Institute, National Institutes of Health; International Agency for
Research on Cancer
FX Financial support : The Golestan Cohort Study was funded by Tehran
University of Medical Sciences (grant No: 81/15) for equipment, staff
transport, and staff salary; by Cancer Research UK (grant No: C20/A5860)
for staff salary; and by the Intramural Research Program of the National
Cancer Institute, National Institutes of Health for equipment, and
through various collaborative research agreements with the International
Agency for Research on Cancer. The study has also received special
support from the Social Security Organization of Iran Golestan Branch.
NR 64
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Z9 11
U1 2
U2 11
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0002-9270
EI 1572-0241
J9 AM J GASTROENTEROL
JI Am. J. Gastroenterol.
PD NOV
PY 2013
VL 108
IS 11
BP 1757
EP 1765
DI 10.1038/ajg.2013.336
PG 9
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 251IQ
UT WOS:000326921800011
PM 24145676
ER
PT J
AU Geraghty, P
Hardigan, AA
Wallace, AM
Mirochnitchenko, O
Thankachen, J
Arellanos, L
Thompson, V
D'Armiento, JM
Foronjy, RF
AF Geraghty, Patrick
Hardigan, Andrew A.
Wallace, Alison M.
Mirochnitchenko, Oleg
Thankachen, Jincy
Arellanos, Leo
Thompson, Victor
D'Armiento, Jeanine M.
Foronjy, Robert F.
TI The Glutathione Peroxidase 1-Protein Tyrosine Phosphatase 1B-Protein
Phosphatase 2A Axis A Key Determinant of Airway Inflammation and
Alveolar Destruction
SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
LA English
DT Article
DE phosphorylation; inflammation; oxidation; kinase
ID OBSTRUCTIVE PULMONARY-DISEASE; CIGARETTE-SMOKE; PROTEIN PHOSPHATASE;
LUNG INFLAMMATION; INNATE IMMUNE; PHOSPHORYLATION; MICE; EXPRESSION;
EMPHYSEMA; CERAMIDE
AB Protein phosphatase-2A (PP2A) is a primary serine-threonine phosphatase that modulates inflammatory responses in asthma and chronic obstructive pulmonary disease (COPD). Despite its importance, the mechanisms that regulate lung PP2A activity remain to be determined. The redox-sensitive enzyme protein tyrosine phosphatase-1B (PTP1B) activates PP2A by dephosphorylating the catalytic subunit of the protein at tyrosine 307. This study aimed to identify how the interaction between the intracellular antioxidant glutathione peroxidase-1 (GPx-1) and PTP1B affected lung PP2A activity and airway inflammation. Experiments using gene silencing techniques in mouse lung or human small airway epithelial cells determined that knocking down PTP1B expression blocked GPx-1's activation of PP2A and negated the anti-inflammatory effects of GPx-1 protein in the lung. Similarly, the expression of human GPx-1 in transgenic mice significantly increased PP2A and PTP1B activities and prevented chronic cigarette smoke-induced airway inflammation and alveolar destruction. GPx-1 knockout mice, however, exhibited an exaggerated emphysema phenotype, correlating with a nonresponsive PP2A pathway. Importantly, GPx-1-PTP1B-PP2A signaling becomes inactivated in advanced lung disease. Indeed, PTP1B protein was oxidized in the lungs of subjects with advanced emphysema, and cigarette smoke did not increase GPx-1 or PTP1B activity within epithelial cells isolated from subjects with COPD, unlike samples of healthy lung epithelial cells. In conclusion, these findings establish that the GPx-1-PTP1B-PP2A axis plays a critical role in countering the inflammatory and proteolytic responses that result in lung-tissue destruction in response to cigarette smoke exposure.
C1 [Geraghty, Patrick; Hardigan, Andrew A.; Foronjy, Robert F.] St Lukes Roosevelt Hosp, New York, NY USA.
[Wallace, Alison M.; Thankachen, Jincy; Arellanos, Leo; Thompson, Victor; D'Armiento, Jeanine M.] Columbia Univ, New York, NY USA.
[Mirochnitchenko, Oleg] NIH, Bethesda, MD 20892 USA.
RP Foronjy, RF (reprint author), St Lukes Hlth Sci Ctr, Dept Med, Antenucci Bldg,432 West 58th St, New York, NY 10019 USA.
EM rforonjy@chpnet.org
FU Flight Attendant Medical Research Institute [YCSA 113380, 24,039,
074,047]; National Institutes of Health [5R01HL098528-04,
5R01HL086936-04]
FX This work was supported by Flight Attendant Medical Research Institute
grant YCSA 113380 and 24,039, Clinical Innovator Award grant 074,047,
and National Institutes of Health grant 5R01HL098528-04 (R. F. F.), and
by National Institutes of Health grant 5R01HL086936-04 (J.M.D.).
NR 44
TC 18
Z9 18
U1 1
U2 7
PU AMER THORACIC SOC
PI NEW YORK
PA 61 BROADWAY, FL 4, NEW YORK, NY 10006 USA
SN 1044-1549
EI 1535-4989
J9 AM J RESP CELL MOL
JI Am. J. Respir. Cell Mol. Biol.
PD NOV
PY 2013
VL 49
IS 5
BP 721
EP 730
DI 10.1165/rcmb.2013-0026OC
PG 10
WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System
SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System
GA 251WV
UT WOS:000326964800005
PM 23590304
ER
PT J
AU Concheiro, M
Anizan, S
Ellefsen, K
Huestis, MA
AF Concheiro, Marta
Anizan, Sebastien
Ellefsen, Kayla
Huestis, Marilyn A.
TI Simultaneous quantification of 28 synthetic cathinones and metabolites
in urine by liquid chromatography-high resolution mass spectrometry
SO ANALYTICAL AND BIOANALYTICAL CHEMISTRY
LA English
DT Article
DE Synthetic cathinones; Urine; LC-HRMS; Stability
ID ENCOUNTERED DESIGNER DRUG; IN-VITRO METABOLISM; RAT URINE; GC-MS;
MEPHEDRONE; 3,4-METHYLENEDIOXYPYROVALERONE; 4-METHYLMETHCATHINONE;
DETECTABILITY; TOXICOLOGY; STABILITY
AB Synthetic cathinones are novel stimulants derived from cathinone, with amphetamines or cocaine-like effects, often labeled "not for human consumption" and considered "legal highs". Emergence of these new designer drugs complicate interpretation of forensic and clinical cases, with introduction of many new analogs designed to circumvent legislation and vary effects and potencies. We developed a method for the simultaneous quantification of 28 synthetic cathinones, including four metabolites, in urine by liquid chromatography coupled to high resolution mass spectrometry (LC-HRMS). These cathinones include cathinone, methcathinone, and synthetic cathinones position-3'-substituted, N-alkyl-substituted, ring-substituted, methylenedioxy-substituted, and pyrrolidinyl-substituted. One mL phosphate buffer pH 6 and 25 mu L IStd solution were combined with 0.25 mL urine, and subjected to solid phase cation exchange extraction (SOLA SCX). The chromatographic reverse-phase separation was achieved with a gradient mobile phase of 0.1 % formic acid in water and in acetonitrile in 20 min. We employed a Q Exactive high resolution mass spectrometer, with compounds identified and quantified by target-MSMS experiments. The assay was linear from 0.5-1 to 100 mu g/L, with limits of detection of 0.25-1 mu g/L. Imprecision (n = 20) was < 15.9 % and accuracy (n = 20) 85.2-118.1 %. Extraction efficiency was 78.9-116.7 % (CV 1.4-16.7 %, n = 5), process efficiency 57.7-104.9 %, and matrix effects from -29.5 % to 1.5 % (CV 1.9-13.1 %, n = 10). Most synthetic cathinones were stable at 4 A degrees C for 72 h (n = 27) and after 3 freeze-thaw cycles (n = 26), but many (n = 19) were not stable at room temperature for 24 h (losses up to -67.6 %). The method was applied to authentic urine specimens from synthetic cathinone users. This method provides a comprehensive confirmation method for 28 synthetic cathinones in urine, with good selectivity and specificity.
C1 [Concheiro, Marta; Anizan, Sebastien; Ellefsen, Kayla; Huestis, Marilyn A.] NIDA, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
RP Huestis, MA (reprint author), NIDA, Intramural Res Program, NIH, 251 Bayview Blvd,Suite 200,Room 05A721, Baltimore, MD 21224 USA.
EM mhuestis@intra.nida.nih.gov
FU Intramural Research Program of the National Institute on Drug Abuse
(NIDA), National Institutes of Health (NIH)
FX This research was supported by the Intramural Research Program of the
National Institute on Drug Abuse (NIDA), National Institutes of Health
(NIH).
NR 32
TC 32
Z9 33
U1 9
U2 71
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 2013
VL 405
IS 29
BP 9437
EP 9448
DI 10.1007/s00216-013-7386-z
PG 12
WC Biochemical Research Methods; Chemistry, Analytical
SC Biochemistry & Molecular Biology; Chemistry
GA 254YN
UT WOS:000327206100014
PM 24196122
ER
PT J
AU Hays, RD
Spritzer, KL
Amtmann, D
Lai, JS
DeWitt, EM
Rothrock, N
DeWalt, DA
Riley, WT
Fries, JF
Krishnan, E
AF Hays, Ron D.
Spritzer, Karen L.
Amtmann, Dagmar
Lai, Jin-Shei
DeWitt, Esi Morgan
Rothrock, Nan
DeWalt, Darren A.
Riley, William T.
Fries, James F.
Krishnan, Eswar
TI Upper-Extremity and Mobility Subdomains From the Patient-Reported
Outcomes Measurement Information System (PROMIS) Adult Physical
Functioning Item Bank
SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION
LA English
DT Article
DE Lower extremity; Psychometrics; Rehabilitation; Upper extremity
ID RESPONSE THEORY
AB Objective: To create upper-extremity and mobility subdomain scores from the Patient-Reported Outcomes Measurement Information System (PROM'S) physical functioning adult item bank.
Design: Expert reviews were used to identify upper-extremity and mobility items from the PROM'S item bank. Psychometric analyses were conducted to assess empirical support for scoring upper-extremity and mobility subdomains.
Setting: Data were collected from the U.S. general population and multiple disease groups via self-administered surveys.
Participants: The sample (N=21,773) included 21,133 English-speaking adults who participated in the PROMIS wave 1 data collection and 640 Spanish-speaking Latino adults recruited separately.
Interventions: Not applicable.
Main Outcome Measures: We used English- and Spanish-language data and, existing PROM'S item parameters for the physical functioning item bank to estimate upper-extremity and mobility scores. In addition, we fit graded response models to calibrate the upper-extremity items and mobility items separately, compare separate to combined calibrations, and produce subdomain scores.
Results: After eliminating items because of local dependency, 16 items remained to assess upper extremity and 17 items to assess mobility. The estimated correlation between upper extremity and mobility was .59 using existing PROMIS physical functioning item parameters (r=.60 using parameters calibrated separately for upper-extremity and mobility items).
Conclusions: Upper-extremity and mobility subdomains shared about 35% of the variance in common, and produced comparable scores whether calibrated separately or together. The identification of the subset of items tapping these 2 aspects of physical functioning and scored using the existing PROMIS parameters provides the option of scoring these subdomains in addition to the overall physical functioning score. (C) 2013 by the American Congress of Rehabilitation Medicine
C1 [Hays, Ron D.; Spritzer, Karen L.] Univ Calif Los Angeles, Div Gen Internal Med & Hlth Serv Res, Dept Med, Los Angeles, CA 90095 USA.
[Hays, Ron D.] RAND Corp, Santa Monica, CA USA.
[Amtmann, Dagmar] Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA.
[Lai, Jin-Shei; Rothrock, Nan] Northwestern Univ, Feinberg Sch Med, Dept Med Social Sci, Chicago, IL 60611 USA.
[DeWitt, Esi Morgan] Cincinnati Childrens Hosp Med Ctr, Dept Pediat, Cincinnati, OH 45229 USA.
[DeWalt, Darren A.] Univ N Carolina, Cecil G Sheps Ctr Hlth Serv Res, Div Gen Med & Clin Epidemiol, Chapel Hill, NC USA.
[Riley, William T.] NCI, Sci Res & Technol Branch, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Fries, James F.; Krishnan, Eswar] Stanford Univ, Dept Med, Sch Med, Stanford, CA 94305 USA.
RP Hays, RD (reprint author), Univ Calif Los Angeles, Div Gen Internal Med & Hlth Serv Res, Dept Med, 911 Broxton Ave, Los Angeles, CA 90095 USA.
EM drhays@ucla.edu
RI AOCID, AO Foundation/R-6455-2016;
OI DeWalt, Darren/0000-0003-2270-751X
FU Statistical Center (Northwestern University) [1U54AR057951]; Technology
Center (Northwestern University) [1U54AR057943]; Network Center
(American Institutes for Research) [1U54AR057926]; University of
Washington, Seattle [1U01AR057954, 1U01AR052171]; University of North
Carolina, Chapel Hill [2U01AR052181]; Children's Hospital of
Philadelphia [1U01AR057956]; Stanford University [2U01AR052158]; Boston
University [1U01AR057929]; University of California, Los Angeles
[1U01AR057936]; University of Pittsburgh [2U01AR052155]; Georgetown
University [U01AR057971]; Children's Hospital Medical Center, Cincinnati
[1U01AR057940]; University of Maryland, Baltimore [1U01AR057967]; Duke
University [2U01AR052186]; UCLA/DREW Project EXPORT, NIMHD
[2P20MD000182]; AO Foundation; [1U01AR057948]
FX PROM'S II was funded by cooperative agreements with a Statistical Center
(Northwestern University, PI: David Cella, PhD, 1U54AR057951), a
Technology Center (Northwestern University, PI: Richard C. Gershon, PhD,
1U54AR057943), a Network Center (American Institutes for Research, PI:
Susan [San] D. Keller, PhD, 1U54AR057926), and 13 primary research sites
that may include more than 1 institution (State University of New York,
Stony Brook, PIs: Joan E. Broderick, PhD, and Arthur A. Stone, PhD,
1U01AR057948; University of Washington, Seattle, PIs: Heidi M. Crane,
MD, MPH, Paul K. Crane, MD, MPH, and Donald L. Patrick, PhD,
1U01AR057954; University of Washington, Seattle, PIs: Dagmar Amtmann,
PhD, and Karon Cook, PhD, 1U01AR052171; University of North Carolina,
Chapel Hill, PI: Darren A. DeWalt, MD, MPH, 2U01AR052181; Children's
Hospital of Philadelphia, PI: Christopher B. Format, MD, PhD,
1U01AR057956; Stanford University, PI: James F. Fries, MD, 2U01AR052158;
Boston University, PIs: Stephen M. Haley, PhD, and David Scott Tulsky,
PhD [University of Michigan, Ann Arbor], 1U01AR057929, University of
California, Los Angeles, Pis: Dinesh Khanna, MD, and Brennan Spiegel,
MD, MSHS, 1U01AR057936; University of Pittsburgh, PI: Paul A. Pilkonis,
PhD, 2U01AR052155; 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, 1U01AR057940; University
of Maryland, Baltimore, PI: Lisa M. Shuiman, MD, 1U01AR057967; and Duke
University, PI: Kevin P. Weinfurt, PhD, 2U01AR052186). The study was
also supported by UCLA/DREW Project EXPORT, NIMHD (grant no.
2P20MD000182) and in part by the AO Foundation.
NR 17
TC 19
Z9 19
U1 1
U2 6
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0003-9993
EI 1532-821X
J9 ARCH PHYS MED REHAB
JI Arch. Phys. Med. Rehabil.
PD NOV
PY 2013
VL 94
IS 11
BP 2291
EP 2296
DI 10.1016/j.apmr.2013.05.014
PG 6
WC Rehabilitation; Sport Sciences
SC Rehabilitation; Sport Sciences
GA 250KV
UT WOS:000326852600035
PM 23751290
ER
PT J
AU Soe, KC
Devaiah, BN
Singer, DS
AF Soe, Katherine C.
Devaiah, Ballachanda N.
Singer, Dinah S.
TI Transcriptional coactivator CIITA, a functional homolog of TAF1, has
kinase activity
SO BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS
LA English
DT Article
DE CIITA; MHC class II; MHC class I; TAF7; Transcription; Kinase
ID II TRANSACTIVATOR CIITA; MHC CLASS-I; ACETYLTRANSFERASE ACTIVITY;
HISTONE H2B; PHOSPHORYLATION; TAF(II)250; EXPRESSION; COMPLEX;
PROMOTERS; REGULATOR
AB The Major Histocompatibility Complex (MHC) class II transactivator (CIITA) mediates activated immune responses and its deficiency results in the Type II Bare Lymphocyte Syndrome. CIITA is a transcriptional coactivator that regulates gamma-interferon-activated transcription of MHC class land class II genes. It is also a functional homolog of TAF1, a component of the general transcription factor complex TFIID. TAF1 and CIITA both possess intrinsic acetyltransferase (AT) activity that is required for transcription initiation. In response to induction by gamma-interferon, CIITA and it's AT activity bypass the requirement for TAF1 AT activity. TAF1 also has kinase activity that is essential for its function. However, no similar activity has been identified for CIITA thus far.
Here we report that CIITA, like TAF1, is a serine-threonine kinase. Its substrate specificity parallels, but does not duplicate, that of TAFI in phosphorylating the TFIID component TAF7, the RAP74 subunit of the general transcription factor TFIIF and histone H2B. Like TAFI, CIITA autophosphorylates, affecting its interaction with TAF7. Additionally, CIITA phosphorylates histone H2B at Ser36, a target of TAF1 that is required for transcription during cell cycle progression and stress response. However, unlike TAF1, CIITA also phosphorylates all the other histones. The identification of this novel kinase activity of CIITA further clarifies its role as a functional homolog of TAF1 which may operate during stress and gamma-IFN activated MHC gene transcription. Published by Elsevier B.V.
C1 [Soe, Katherine C.; Devaiah, Ballachanda N.; Singer, Dinah S.] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA.
RP Singer, DS (reprint author), NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA.
EM Dinah.singer@nih.gov
FU NIH, National Cancer Institute, Center for Cancer Research
FX We thank Dr. Jenny Ting for her generous gift of CIITA mutants, Dr. Paul
Roche for technical advice and Dr. Ming Zhou for performing the mass
spec. We thank members of the lab for helpful discussions. We also thank
Drs. Keiko Ozato, Paul Roche and Stoney Simons Jr. for their critical
review of this manuscript. This research was supported by the Intramural
Research Program of the NIH, National Cancer Institute, Center for
Cancer Research.
NR 26
TC 3
Z9 7
U1 1
U2 4
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1874-9399
EI 0006-3002
J9 BBA-GENE REGUL MECH
JI Biochim. Biophys. Acta-Gene Regul. Mech.
PD NOV
PY 2013
VL 1829
IS 11
BP 1184
EP 1190
DI 10.1016/j.bbagrm.2013.09.001
PG 7
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 253SD
UT WOS:000327108700003
PM 24036077
ER
PT J
AU Lewis, BA
AF Lewis, Brian A.
TI O-GlcNAcylation at promoters, nutrient sensors, and transcriptional
regulation
SO BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS
LA English
DT Review
DE Transcription; RNA polymerase II; O-GlcNAc; Nutrient sensor
ID RNA-POLYMERASE-II; N-ACETYLGLUCOSAMINE TRANSFERASE; EMBRYONIC
STEM-CELLS; CIRCADIAN CLOCK; GLCNAC TRANSFERASE; INSULIN-RESISTANCE;
TERMINAL DOMAIN; CHRONIC DISEASE; HISTONE H3; IN-VIVO
AB Post-translational modifications play important roles in transcriptional regulation. Among the less understood PTMs is O-GlcNAcylation. Nevertheless, O-GlcNAcylation in the nucleus is found on hundreds of transcription factors and coactivators and is often found in a mutually exclusive ying-yang relationship with phosphorylation. O-GlcNAcylation also links cellular metabolism directly to the proteome, serving as a conduit of metabolic information to the nucleus. This review serves as a brief introduction to O-GlcNAcylation, emphasizing its important thematic roles in transcriptional regulation, and highlights several recent and important additions to the literature that illustrate the connections between O-GlcNAc and transcription. Published by Elsevier B.V.
C1 NCI, Metab Branch, CCR, NIH, Bethesda, MD 20892 USA.
RP Lewis, BA (reprint author), NCI, Metab Branch, CCR, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM lewisbri@mail.nih.gov
FU Intramural Program/CCR/NCI/NIH
FX BAL would like to thank Drs. Alfonzo Fernandez and Melissa Resto for the
suggestions and comments. BAL acknowledges the funding from the
Intramural Program/CCR/NCI/NIH.
NR 70
TC 14
Z9 14
U1 1
U2 15
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1874-9399
EI 0006-3002
J9 BBA-GENE REGUL MECH
JI Biochim. Biophys. Acta-Gene Regul. Mech.
PD NOV
PY 2013
VL 1829
IS 11
BP 1202
EP 1206
DI 10.1016/j.bbagrm.2013.09.003
PG 5
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 253SD
UT WOS:000327108700005
PM 24076017
ER
PT J
AU Barrett, AJ
AF Barrett, A. John
TI Immune Recovery in Pediatric Transplantation: Can T Cell-Depleted
Peripheral Blood Stem Cell Transplantation Beat Cord Blood
Transplantation?
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Editorial Material
C1 [Barrett, A. John] NHLBI, Allogene Stem Cell Transplantat Sect, Hematol Branch, NIH, Bethesda, MD 20892 USA.
RP Barrett, AJ (reprint author), NHLBI, Hematol Branch, CRC, Room 3-5330,10 Ctr Dr, Bethesda, MD 20892 USA.
EM barrettj@nhlbi.nih.gov
NR 10
TC 0
Z9 0
U1 0
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 2013
VL 19
IS 11
BP 1531
EP 1532
DI 10.1016/j.bbmt.2013.09.002
PG 2
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA 250KL
UT WOS:000326851600001
PM 24035781
ER
PT J
AU Gress, RE
Miller, JS
Battiwalla, M
Bishop, MR
Giralt, SA
Hardy, NM
Kroger, N
Wayne, AS
Landau, DA
Wu, CJ
AF Gress, Ronald E.
Miller, Jeffrey S.
Battiwalla, Minoo
Bishop, Michael R.
Giralt, Sergio A.
Hardy, Nancy M.
Kroeger, Nicolaus
Wayne, Alan S.
Landau, Dan A.
Wu, Catherine J.
TI Proceedings from the National Cancer Institute's Second International
Workshop on the Biology, Prevention, and Treatment of Relapse after
Hematopoietic Stem Cell Transplantation: Part I. Biology of Relapse
after Transplantation
SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION
LA English
DT Article
DE Stem cell transplantation; Relapse; Allogeneic; Prevention; Biology;
Treatment
ID NATURAL-KILLER-CELLS; CHRONIC LYMPHOCYTIC-LEUKEMIA; T-CELLS; INTENSIVE
CHEMOTHERAPY; MULTIPLE-MYELOMA; CLONAL EVOLUTION; BREAST-CANCER; NK
CELLS; CYTOMEGALOVIRUS; RECONSTITUTION
AB In the National Cancer Institute's Second Workshop on the Biology, Prevention, and Treatment of Relapse after Hematopoietic Stem Cell Transplantation, the Scientific/Educational Session on the Biology of Relapse discussed recent advances in understanding some of the host-, disease-, and transplantation-related contributions to relapse, emphasizing concepts with potential therapeutic implications. Relapse after hematopoietic stem cell transplantation (HSCT) represents tumor escape, from the cytotoxic effects of the conditioning regimen and from immunologic control mediated by reconstituted lymphocyte populations. Factors influencing the biology of the therapeutic graft-versus-malignancy (GVM) effect-and relapse-include conditioning regimen effects on lymphocyte populations and homeostasis, immunologic niches, and the tumor microenvironment; reconstitution of lymphocyte populations and establishment of functional immune competence; and genetic heterogeneity within the malignancy defining potential for clonal escape. Recent developments in T cell and natural killer cell homeostasis and reconstitution are reviewed, with implications for prevention and treatment of relapse, as is the application of modern genome sequencing to defining the biologic basis of GVM, clonal escape, and relapse after HSCT. Published by Elsevier Inc. on behalf of American Society for Blood and Marrow Transplantation.
C1 [Gress, Ronald E.; Hardy, Nancy M.] NCI, Expt Transplantat & Immunol Branch, NIH, Ctr Canc Res, Bethesda, MD 20892 USA.
[Miller, Jeffrey S.] Univ Minnesota, Ctr Canc, Minneapolis, MN USA.
[Battiwalla, Minoo] NHLBI, Hematol Branch, Bethesda, MD 20892 USA.
[Bishop, Michael R.] Univ Chicago, Hematol Oncol Sect, Chicago, IL 60637 USA.
[Giralt, Sergio A.] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10021 USA.
[Kroeger, Nicolaus] Univ Med Ctr Hamburg Eppendorf, Dept Stem Cell Transplantat, Hamburg, Germany.
[Wayne, Alan S.] NCI, Pediat Oncol Branch, NIH, Ctr Canc Res, Bethesda, MD 20892 USA.
[Landau, Dan A.; Wu, Catherine J.] Dana Farber Canc Inst, Canc Vaccine Ctr, Boston, MA 02115 USA.
[Landau, Dan A.; Wu, Catherine J.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA.
RP Hardy, NM (reprint author), NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, Hatfield Clin Res Ctr, 10 Ctr Dr,Room 3E-3330, Bethesda, MD 20892 USA.
EM hardyn@mail.nih.gov
OI Miller, Jeffrey S/0000-0002-0339-4944
FU National Institutes of Health: the National Cancer Institute/Center for
Cancer Research; National Institutes of Health: National Heart, Lung and
Blood Institute
FX Supported in part by the Intramural Research Programs of the National
Institutes of Health: the National Cancer Institute/Center for Cancer
Research and the National Heart, Lung and Blood Institute.
NR 48
TC 8
Z9 8
U1 0
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1083-8791
EI 1523-6536
J9 BIOL BLOOD MARROW TR
JI Biol. Blood Marrow Transplant.
PD NOV
PY 2013
VL 19
IS 11
BP 1537
EP 1545
DI 10.1016/j.bbmt.2013.08.010
PG 9
WC Hematology; Immunology; Transplantation
SC Hematology; Immunology; Transplantation
GA 250KL
UT WOS:000326851600004
PM 24018395
ER
PT J
AU Wardell, JR
Hodgkinson, KM
Binder, AK
Seymour, KA
Korach, KS
Vanderhyden, BC
Freiman, RN
AF Wardell, Jennifer R.
Hodgkinson, Kendra M.
Binder, April K.
Seymour, Kimberly A.
Korach, Kenneth S.
Vanderhyden, Barbara C.
Freiman, Richard N.
TI Estrogen Responsiveness of the TFIID Subunit TAF4B in the Normal Mouse
Ovary and in Ovarian Tumors
SO BIOLOGY OF REPRODUCTION
LA English
DT Article
DE estradiol/estradiol receptor; ovarian cancer; ovary; premature ovarian
failure; TAF4B
ID HORMONE REPLACEMENT THERAPY; TBP-ASSOCIATED FACTOR; GENE-EXPRESSION;
RECEPTOR-BETA; TARGET GENES; IN-VIVO; RISK-FACTORS; CELL-GROWTH; CANCER;
ALPHA
AB Estrogen signaling in the ovary is a fundamental component of normal ovarian function, and evidence also indicates that excessive estrogen is a risk factor for ovarian cancer. We have previously demonstrated that the gonadally enriched TFIID subunit TAF4B, a paralog of the general transcription factor TAF4A, is required for fertility in mice and for the proliferation of ovarian granulosa cells following hormonal stimulation. However, the relationship between TAF4B and estrogen signaling in the normal ovary or during ovarian tumor initiation and progression has yet to be defined. Herein, we show that Taf4b mRNA and TAF4B protein, but not Taf4a mRNA or TAF4A protein, are increased in whole ovaries and granulosa cells of the ovary after exposure to 17beta-estradiol or the synthetic estrogen diethylstilbestrol and that this response occurs within hours after stimulation. Furthermore, this increase occurs via nuclear estrogen receptors both in vivo and in a mouse granulosa cancer cell line, NT-1. We observe a significant increase in Taf4b mRNA in estrogen-supplemented mouse ovarian tumors, which correlates with diminished survival of these mice. These data highlight the novel response of the general transcription factor TAF4B to estrogen in the normal ovary and during ovarian tumor progression in the mouse, suggesting its potential role in regulating actions downstream of estrogen stimulation.
C1 [Wardell, Jennifer R.; Freiman, Richard N.] Brown Univ, Pathobiol Grad Program, Providence, RI 02912 USA.
[Seymour, Kimberly A.; Freiman, Richard N.] Brown Univ, Dept Mol & Cellular Biol & Biochem, Providence, RI 02912 USA.
[Hodgkinson, Kendra M.; Vanderhyden, Barbara C.] Univ Ottawa, Dept Cellular & Mol Med, Ottawa, ON, Canada.
[Hodgkinson, Kendra M.; Vanderhyden, Barbara C.] Ottawa Hosp Res Inst, Ctr Canc Therapeut, Ottawa, ON, Canada.
[Binder, April K.; Korach, Kenneth S.] Natl Inst Environm Hlth Sci, Lab Reprod & Dev Toxicol, Res Triangle Pk, NC USA.
RP Freiman, RN (reprint author), Brown Univ, Dept Mol & Cellular Biol & Biochem, 70 Ship St, Providence, RI 02912 USA.
EM Richard_Freiman@Brown.edu
OI Korach, Kenneth/0000-0002-7765-418X
FU American Cancer Society Research Scholar [DMC-117629]; National
Institutes of Health [R01 HD065445]; National Institutes of Health
Center of Biomedical Research Excellence Center for Cancer Signaling
Networks [RR031153]; Canadian Institutes of Health Research
[MOP-111194]; National Institute of Environmental Health
Sciences/National Institutes of Health Intramural Research Program
[Z01ES70065]
FX Supported by American Cancer Society Research Scholar Grant DMC-117629
to R.N.F.; by National Institutes of Health grant R01 HD065445 to
R.N.F.; by National Institutes of Health Center of Biomedical Research
Excellence Center for Cancer Signaling Networks grant RR031153 to
R.N.F.; by Canadian Institutes of Health Research Grant MOP-111194 to B.
C. V.; and by National Institute of Environmental Health
Sciences/National Institutes of Health Intramural Research Program grant
Z01ES70065 to K. S. K. Presented in part at a poster session during the
45th Annual Meeting of the Society for the Study of Reproduction and the
18th Ovarian Workshop, August 12-15, 2012, State College, Pennsylvania,
and during the 46th Annual Meeting of the Society for the Study of
Reproduction, July 22-26, 2013, Montreal, Quebec, Canada.
NR 47
TC 2
Z9 2
U1 0
U2 2
PU SOC STUDY REPRODUCTION
PI MADISON
PA 1691 MONROE ST,SUITE # 3, MADISON, WI 53711-2021 USA
SN 0006-3363
EI 1529-7268
J9 BIOL REPROD
JI Biol. Reprod.
PD NOV
PY 2013
VL 89
IS 5
AR 116
DI 10.1095/biolreprod.113.111336
PG 9
WC Reproductive Biology
SC Reproductive Biology
GA 254CF
UT WOS:000327139300010
PM 24068106
ER
PT J
AU Wood, WA
Chai, X
Weisdorf, D
Martin, PJ
Cutler, C
Inamoto, Y
Wolff, D
Pavletic, SZ
Pidala, J
Palmer, JM
Arora, M
Arai, S
Jagasia, M
Storer, B
Lee, SJ
Mitchell, S
AF Wood, W. A.
Chai, X.
Weisdorf, D.
Martin, P. J.
Cutler, C.
Inamoto, Y.
Wolff, D.
Pavletic, S. Z.
Pidala, J.
Palmer, J. M.
Arora, M.
Arai, S.
Jagasia, M.
Storer, B.
Lee, S. J.
Mitchell, S.
TI Comorbidity burden in patients with chronic GVHD
SO BONE MARROW TRANSPLANTATION
LA English
DT Article
DE chronic GVHD; comorbidities; outcomes; allogeneic hematopoietic cell
transplantation
ID HEMATOPOIETIC-CELL TRANSPLANTATION; VERSUS-HOST-DISEASE; REPORTED
OUTCOMES; REDUCED-INTENSITY; PHYSICAL FUNCTION; INDEX; LYMPHOMA;
MORTALITY; SEVERITY; LEUKEMIA
AB Chronic GVHD (cGVHD) is associated with mortality, disability and impaired quality of life. Understanding the role of comorbidity in patients with cGVHD is important both for prognostication and potentially for tailoring treatments based on mortality risks. In a prospective cohort study of patients with cGVHD (n = 239), we examined the performance of two comorbidity scales, the Functional Comorbidity Index (FCI) and the Hematopoietic Cell Transplantation-specific Comorbidity Index (HCT-CI). Both scales detected a higher number of comorbidities at cGVHD cohort enrollment than pre-hematopoietic cell transplant (HCT) (P<0.001). Higher HCT-CI scores at the time of cGVHD cohort enrollment were associated with higher non-relapse mortality (HR: 1.21:1.04-1.42, P = 0.01). For overall mortality, we detected an interaction with platelet count. Higher HCT-CI scores at enrollment were associated with an increased risk of overall mortality when the platelet count was <= 100 000/mu L (HR: 2.01:1.20-3.35, P = 0.01), but not when it was >100 000/mu L (HR: 1.05:0.90-1.22, P = 0.53). Comorbidity scoring may help better to predict survival outcomes in patients with cGVHD. Further studies to understand vulnerability unrelated to cGVHD activity in this patient population are needed.
C1 [Wood, W. A.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA.
[Chai, X.; Martin, P. J.; Inamoto, Y.; Storer, B.; Lee, S. J.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA.
[Weisdorf, D.; Arora, M.] Univ Minnesota, Blood & Marrow Transplant Program, Minneapolis, MN USA.
[Cutler, C.] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Wolff, D.] Univ Regensburg, Dept Hematol & Clin Oncol, D-93053 Regensburg, Germany.
[Pavletic, S. Z.; Mitchell, S.] NCI, NIH, Bethesda, MD 20892 USA.
[Pidala, J.] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA.
[Palmer, J. M.] Med Coll Wisconsin, Div Hematol Oncol, Milwaukee, WI 53226 USA.
[Arai, S.] Stanford Univ, Med Ctr, Div Blood & Marrow Transplantat, Stanford, CA 94305 USA.
[Jagasia, M.] Vanderbilt Univ, Med Ctr, Dept Med, Nashville, TN USA.
RP Wood, WA (reprint author), Univ N Carolina, Lineberger Comprehens Canc Ctr, Phys Off Bldg,170 Manning Dr, Chapel Hill, NC 27599 USA.
EM wawood@med.unc.edu
OI Wood, William/0000-0001-7439-2543
FU National Institutes of Health/National Cancer Institute [CA 118953,
KL2TR000084]
FX This work was supported by National Institutes of Health/National Cancer
Institute grant CA 118953 as well as grant KL2TR000084.
NR 22
TC 8
Z9 8
U1 1
U2 1
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0268-3369
EI 1476-5365
J9 BONE MARROW TRANSPL
JI Bone Marrow Transplant.
PD NOV
PY 2013
VL 48
IS 11
BP 1429
EP 1436
DI 10.1038/bmt.2013.70
PG 8
WC Biophysics; Oncology; Hematology; Immunology; Transplantation
SC Biophysics; Oncology; Hematology; Immunology; Transplantation
GA 250WR
UT WOS:000326887900010
PM 23665819
ER
PT J
AU Siziopikou, KP
Anderson, SJ
Cobleigh, MA
Julian, TB
Arthur, DW
Zheng, P
Mamounas, EP
Pajon, ER
Behrens, RJ
Eakle, JF
Leasure, NC
Atkins, JN
Polikoff, JA
Seay, TE
McCaskill-Stevens, WJ
Rabinovitch, R
Costantino, JP
Wolmark, N
AF Siziopikou, Kalliopi P.
Anderson, Stewart J.
Cobleigh, Melody A.
Julian, Thomas B.
Arthur, Douglas W.
Zheng, Ping
Mamounas, Eleftherios P.
Pajon, Eduardo R.
Behrens, Robert J.
Eakle, Janice F.
Leasure, Nick C.
Atkins, James N.
Polikoff, Jonathan A.
Seay, Thomas E.
McCaskill-Stevens, Worta J.
Rabinovitch, Rachel
Costantino, Joseph P.
Wolmark, Norman
TI Preliminary results of centralized HER2 testing in ductal carcinoma in
situ (DCIS): NSABP B-43
SO BREAST CANCER RESEARCH AND TREATMENT
LA English
DT Article
DE DCIS; Non-invasive breast cancer; HER2; Clinical trials
ID INTRADUCTAL BREAST-CANCER; SURGICAL ADJUVANT BREAST; BIOLOGICAL MARKERS;
PROTEIN OVEREXPRESSION; MORPHOLOGIC FEATURES; MONOCLONAL-ANTIBODY;
MOLECULAR-FEATURES; CELL-PROLIFERATION; HORMONE-RECEPTORS; HISTOLOGICAL
TYPE
AB NSABP B-43 is the first prospective, randomized phase III multi-institution clinical trial targeting high-risk, HER2-positive DCIS. It compares whole breast irradiation alone with WBI given concurrently with trastuzumab in women with HER2-positive DCIS treated by lumpectomy. The primary aim is to determine if trastuzumab plus radiation will reduce in-breast tumor recurrence. HER2-positive DCIS was previously estimated at > 50 %, occurring primarily in ER-negative, comedo-type DCIS of high nuclear grade. There has been no documented centralized multi-institutional HER2 analysis of DCIS. NSABP B-43 provides a unique opportunity to evaluate this in a large cohort of DCIS patients. Patients undergoing lumpectomy for DCIS without evidence of an invasive component are eligible. A central review of each patient's pure DCIS lesion is carried out by immunohistochemistry analysis. If the lesion is 2+, FISH analysis is performed. Patients whose tumors are HER2 3+ or FISH-positive are randomly assigned to receive two doses of trastuzumab during WBI or WBI alone. NSABP B-43 opened 11/9/08. As of 7/31/2013, 5,861 patients have had specimens received centrally, and 5,645 of those had analyzable blocks; 1,969 (34.9 %) were HER2 positive. A total of 1,428 patients have been accrued, 1,137 (79.6 %) of whom have follow-up information. The average follow-up time for the 1,137 patients is 23.3 months. No grade 4 or 5 toxicity has been observed. In NSABP B-43 the HER2-positive rate for pure DCIS among patients undergoing breast-preserving surgery is 34.9 %, lower than the previously reported rate. No trastuzumab-related safety signals have been observed. Interest in this trial has been robust.
C1 [Siziopikou, Kalliopi P.; Anderson, Stewart J.; Cobleigh, Melody A.; Julian, Thomas B.; Arthur, Douglas W.; Mamounas, Eleftherios P.; Pajon, Eduardo R.; Behrens, Robert J.; Eakle, Janice F.; Leasure, Nick C.; Atkins, James N.; Polikoff, Jonathan A.; Seay, Thomas E.; McCaskill-Stevens, Worta J.; Rabinovitch, Rachel; Costantino, Joseph P.; Wolmark, Norman] Natl Surg Adjuvant Breast & Bowel Project NSABP, Pittsburgh, PA USA.
[Siziopikou, Kalliopi P.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA.
[Anderson, Stewart J.; Zheng, Ping; Costantino, Joseph P.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, NSABP Biostat Ctr, Pittsburgh, PA 15261 USA.
[Cobleigh, Melody A.] Rush Univ, Med Ctr, Chicago, IL 60612 USA.
[Julian, Thomas B.; Wolmark, Norman] Allegheny Gen Hosp, Allegheny Canc Ctr, Pittsburgh, PA 15212 USA.
[Arthur, Douglas W.] Virginia Commonwealth Univ, Richmond, VA USA.
[Mamounas, Eleftherios P.] Aultman Hosp, Canton, OH USA.
[Pajon, Eduardo R.] Colorado Canc Res Program, Denver, CO USA.
[Behrens, Robert J.] Iowa Oncol Res Assoc, Des Moines, IA USA.
[Eakle, Janice F.] Florida Canc Specialists, Sarasota, FL USA.
[Leasure, Nick C.] Reading Reg Hosp, McGlinn Family Canc Ctr, W Reading, PA USA.
[Atkins, James N.] Southeast Canc Control Consortium CCOP, Winston Salem, NC USA.
[Polikoff, Jonathan A.] Kaiser Permanente So Calif, San Diego, CA USA.
[Seay, Thomas E.] Atlanta Reg Community Clin Oncol Program, Atlanta, GA USA.
[McCaskill-Stevens, Worta J.] NCI, Canc Prevent Div, Bethesda, MD 20892 USA.
[Rabinovitch, Rachel] Univ Colorado, Aurora, CO USA.
RP Julian, TB (reprint author), Allegheny Gen Hosp, Allegheny Canc Ctr, 320 E N Ave, Pittsburgh, PA 15212 USA.
EM tjulian@wpahs.org
OI Anderson, Stewart/0000-0001-8948-0650
FU Genentech, Inc.; [NCI-U10-CA-12027]; [U10-CA-37377]; [U10-CA-69974];
[U10-CA-69651]; [U10-CA-21661]
FX This work was supported by NCI-U10-CA-12027, U10-CA-37377, U10-CA-69974,
U10-CA-69651, U10-CA-21661, and Genentech, Inc., a member of the Roche
Group. The authors wish to acknowledge Dr. Luis Chu, and the following
pathologists for interpreting HER2 tests: Drs. Pincas Bitterman, Paolo
Gattuso, and Ritu Ghai, Rush University Medical Center.
NR 43
TC 16
Z9 17
U1 0
U2 4
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0167-6806
EI 1573-7217
J9 BREAST CANCER RES TR
JI Breast Cancer Res. Treat.
PD NOV
PY 2013
VL 142
IS 2
BP 415
EP 421
DI 10.1007/s10549-013-2755-z
PG 7
WC Oncology
SC Oncology
GA 253JB
UT WOS:000327079800016
PM 24202240
ER
PT J
AU Magill, SS
Klompas, M
Balk, R
Burns, SM
Deutschman, CS
Diekema, D
Fridkin, S
Greene, L
Guh, A
Gutterman, D
Hammer, B
Henderson, D
Hess, DR
Hill, NS
Horan, T
Kollef, M
Levy, M
Septimus, E
VanAntwerpen, C
Wright, D
Lipsett, P
AF Magill, Shelley S.
Klompas, Michael
Balk, Robert
Burns, Suzanne M.
Deutschman, Clifford S.
Diekema, Daniel
Fridkin, Scott
Greene, Linda
Guh, Alice
Gutterman, David
Hammer, Beth
Henderson, David
Hess, Dean R.
Hill, Nicholas S.
Horan, Teresa
Kollef, Marin
Levy, Mitchell
Septimus, Edward
VanAntwerpen, Carole
Wright, Don
Lipsett, Pamela
TI Developing a New, National Approach to Surveillance for
Ventilator-Associated Events Executive Summary
SO CHEST
LA English
DT Article
C1 [Fridkin, Scott; Guh, Alice; Horan, Teresa] Ctr Dis Control & Prevent, Div Healthcare Qual Promot, Atlanta, GA 30329 USA.
[Klompas, Michael] Harvard Univ, Sch Med, Dept Populat Med, Boston, MA USA.
[Klompas, Michael] Harvard Pilgrim Hlth Care Inst, Boston, MA USA.
[Klompas, Michael] Brigham & Womens Hosp, Infect Control Dept, Boston, MA 02115 USA.
[Klompas, Michael] Soc Healthcare Epidemiol Amer, Arlington, VA USA.
[Balk, Robert] Rush Univ, Sch Med, Div Pulm & Crit Care Med, Chicago, IL 60612 USA.
[Balk, Robert; Burns, Suzanne M.; Deutschman, Clifford S.; Gutterman, David; Hammer, Beth; Hill, Nicholas S.; Kollef, Marin; Levy, Mitchell; Lipsett, Pamela] Amer Thorac Soc, Soc Crit Care Med, Crit Care Soc Collaborat Amer Assoc Crit Care Nur, Amer Coll Chest Phys, Philadelphia, PA USA.
[Burns, Suzanne M.] Univ Virginia, Sch Nursing Crit & Acute Care, Charlottesville, VA USA.
[Deutschman, Clifford S.] Univ Penn, Perelman Sch Med, Dept Anesthesiol & Crit Care, Philadelphia, PA 19104 USA.
[Diekema, Daniel] Univ Iowa, Carver Coll Med, Div Infect Dis, Iowa City, IA USA.
[Diekema, Daniel] Healthcare Infect Control Practices Advisory Comm, Surveillance Working Grp, Atlanta, GA USA.
[Greene, Linda] Rochester Gen Hlth Syst, Infect Prevent & Control Dept, Rochester, NY USA.
[Greene, Linda] Assoc Professionals Infect Control & Epidemiol, Washington, DC USA.
[Gutterman, David] Med Coll Wisconsin, Dept Med, Milwaukee, WI 53226 USA.
[Hammer, Beth] Zablocki VA Med Ctr, Dept Cardiol, Milwaukee, WI USA.
[Henderson, David] NIH, Hosp Epidemiol & Qual Improvement, Ctr Clin, Bethesda, MD 20892 USA.
[Hess, Dean R.] Massachusetts Gen Hosp, Dept Resp Care, Boston, MA 02114 USA.
[Hess, Dean R.] Harvard Univ, Sch Med, Dept Anesthesia, Boston, MA USA.
[Hess, Dean R.] Amer Assoc Resp Care, Irving, TX USA.
[Hill, Nicholas S.] Tufts Med Ctr, Div Pulm & Crit Care Med, Boston, MA USA.
[Kollef, Marin] Washington Univ, Div Pulm & Crit Care Med, St Louis, MO USA.
[Levy, Mitchell] Brown Univ, Rhode Isl Hosp, Warren Alpert Med Sch, Div Pulm Crit Care & Sleep, Providence, RI 02903 USA.
[Septimus, Edward] Texas A&M Hlth Sci Ctr, Dept Internal Med, College Stn, TX USA.
[Septimus, Edward] Infect Dis Soc Amer, Arlington, VA USA.
[VanAntwerpen, Carole] New York State Dept Hlth, Bur Healthcare Associated Infect, Albany, NY USA.
[VanAntwerpen, Carole] Council State & Territorial Epidemiologists, Atlanta, GA USA.
[Wright, Don] US Dept Hlth & Human Serv, Off Dis Prevent & Hlth Promot, Washington, DC USA.
[Lipsett, Pamela] Johns Hopkins Univ, Sch Med, Dept Surg, Baltimore, MD 21205 USA.
RP Magill, SS (reprint author), Ctr Dis Control & Prevent, Div Healthcare Qual Promot, 1600 Clifton Rd,MS A-24, Atlanta, GA 30329 USA.
EM smagill@cdc.gov
OI Diekema, Daniel/0000-0003-1273-0724
NR 2
TC 6
Z9 6
U1 0
U2 1
PU AMER COLL CHEST PHYSICIANS
PI GLENVIEW
PA 2595 PATRIOT BLVD, GLENVIEW, IL 60026 USA
SN 0012-3692
J9 CHEST
JI Chest
PD NOV
PY 2013
VL 144
IS 5
BP 1448
EP 1452
DI 10.1378/chest.13-1640
PG 5
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA 254DI
UT WOS:000327143700010
PM 24189858
ER
PT J
AU Marx, GR
Shirali, G
Levine, JC
Guey, LT
Cnota, JF
Baffa, JM
Border, WL
Colan, S
Ensing, G
Friedberg, MK
Goldberg, DJ
Idriss, SF
John, JB
Lai, WW
Lu, MM
Menon, SC
Ohye, RG
Saudek, D
Wong, PC
Pearson, GD
AF Marx, Gerald R.
Shirali, Girish
Levine, Jami C.
Guey, Lin T.
Cnota, James F.
Baffa, Jeanne M.
Border, William L.
Colan, Steve
Ensing, Gregory
Friedberg, Mark K.
Goldberg, David J.
Idriss, Salim F.
John, J. Blaine
Lai, Wyman W.
Lu, Minmin
Menon, Shaji C.
Ohye, Richard G.
Saudek, David
Wong, Pierre C.
Pearson, Gail D.
CA Pediat Heart Network Investigators
TI Multicenter Study Comparing Shunt Type in the Norwood Procedure for
Single-Ventricle Lesions Three-Dimensional Echocardiographic Analysis
SO CIRCULATION-CARDIOVASCULAR IMAGING
LA English
DT Article
DE echocardiography; heart defects; congenital; pediatrics
ID LEFT-HEART SYNDROME; BIDIRECTIONAL CAVOPULMONARY ANASTOMOSIS; CARDIAC
MAGNETIC-RESONANCE; EJECTION FRACTION; 3D ECHOCARDIOGRAPHY; IN-VITRO;
VOLUME; MASS; ADAPTATION; VALIDATION
AB Background The Pediatric Heart Network's Single Ventricle Reconstruction (SVR) trial randomized infants with single right ventricles (RVs) undergoing a Norwood procedure to a modified Blalock-Taussig or RV-to-pulmonary artery shunt. This report compares RV parameters in the 2 groups using 3-dimensional echocardiography.
Methods and Results Three-dimensional echocardiography studies were obtained at 10 of 15 SVR centers. Of the 549 subjects, 314 underwent 3-dimensional echocardiography studies at 1 to 4 time points (pre-Norwood, post-Norwood, pre-stage II, and 14 months) for a total of 757 3-dimensional echocardiography studies. Of these, 565 (75%) were acceptable for analysis. RV volume, mass, mass:volume ratio, ejection fraction, and severity of tricuspid regurgitation did not differ by shunt type. RV volumes and mass did not change after the Norwood, but increased from pre-Norwood to pre-stage II (end-diastolic volume [milliliters]/body surface area [BSA](1.3), end-systolic volume [milliliters]/BSA(1.3), and mass [grams]/BSA(1.3) mean difference [95% confidence interval]=25.0 [8.7-41.3], 19.3 [8.3-30.4], and 17.9 [7.3-28.5], then decreased by 14 months (end-diastolic volume/BSA(1.3), end-systolic volume/BSA(1.3), and mass/BSA(1.3) mean difference [95% confidence interval]=-24.4 [-35.0 to -13.7], -9.8 [-17.9 to -1.7], and -15.3 [-22.0 to -8.6]. Ejection fraction decreased from pre-Norwood to pre-stage II (mean difference [95% confidence interval]=-3.7 [-6.9 to -0.5]), but did not decrease further by 14 months.
Conclusions We found no statistically significant differences between study groups in 3-dimensional echocardiography measures of RV size and function, or magnitude of tricuspid regurgitation. Volume unloading was seen after stage II, as expected, but ejection fraction did not improve. This study provides insights into the remodeling of the operated univentricular RV in infancy.
C1 [Marx, Gerald R.; Levine, Jami C.; Colan, Steve] Boston Childrens Hosp, Boston, MA USA.
[Shirali, Girish] Childrens Mercy Hosp & Clin, Kansas City, MO USA.
[Guey, Lin T.; Lu, Minmin] New England Res Inst, Watertown, MA 02172 USA.
[Cnota, James F.] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH USA.
[Baffa, Jeanne M.] Alfred I DuPont Hosp Children, Wilmington, DE USA.
[Border, William L.] Emory Univ, Sch Med, Atlanta, GA USA.
[Ensing, Gregory; Ohye, Richard G.] Univ Michigan, Ann Arbor, MI 48109 USA.
[Friedberg, Mark K.] Hosp Sick Children, Toronto, ON M5G 1X8, Canada.
[Friedberg, Mark K.] Univ Toronto, Toronto, ON, Canada.
[Goldberg, David J.] Childrens Hosp Philadelphia, Dept Pediat, Philadelphia, PA USA.
[Idriss, Salim F.] Duke Univ, Med Ctr, Durham, NC USA.
[John, J. Blaine] Congenital Heart Inst Florida Pediat, Tampa, FL USA.
[Lai, Wyman W.] Columbia Univ, Med Ctr, New York, NY USA.
[Menon, Shaji C.] Univ Utah, Salt Lake City, UT USA.
[Saudek, David] Med Coll Wisconsin, Milwaukee, WI 53226 USA.
[Wong, Pierre C.] Childrens Hosp Los Angeles, Los Angeles, CA USA.
[Pearson, Gail D.] NHLBI, NIH, Bethesda, MD 20892 USA.
RP Pearson, GD (reprint author), NHLBI, 6701 Rockledge Dr,Room 8132, Bethesda, MD 20892 USA.
EM pearsong@mail.nih.gov
FU National Heart, Lung, and Blood Institute, National Institutes of Health
[HL068269, HL068270, HL068279, HL068281, HL068285, HL068288, HL068290,
HL068292, HL085057]
FX This study was supported by grants (HL068269, HL068270, HL068279,
HL068281, HL068285, HL068288, HL068290, HL068292, and HL085057) from the
National Heart, Lung, and Blood Institute, National Institutes of
Health. The views of the authors are their own and do not necessarily
reflect an official position of the National Heart, Lung, and Blood
Institute.
NR 24
TC 5
Z9 5
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1941-9651
EI 1942-0080
J9 CIRC-CARDIOVASC IMAG
JI Circ.-Cardiovasc. Imaging
PD NOV
PY 2013
VL 6
IS 6
BP 934
EP 942
DI 10.1161/CIRCIMAGING.113.000304
PG 9
WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical
Imaging
SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine &
Medical Imaging
GA 253UI
UT WOS:000327114400019
PM 24097422
ER
PT J
AU Olivieri, LJ
Baba, RY
Arai, AE
Bandettini, WP
Rosing, DR
Bakalov, V
Sachdev, V
Bondy, CA
AF Olivieri, Laura J.
Baba, Ridhwan Y.
Arai, Andrew E.
Bandettini, W. Patricia
Rosing, Douglas R.
Bakalov, Vladimir
Sachdev, Vandana
Bondy, Carolyn A.
TI Spectrum of Aortic Valve Abnormalities Associated With Aortic Dilation
Across Age Groups in Turner Syndrome
SO CIRCULATION-CARDIOVASCULAR IMAGING
LA English
DT Article
DE abnormalities; aorta; echocardiography; magnetic resonance imaging;
Turner syndrome
ID CARDIOVASCULAR MALFORMATIONS; DILATATION; DISSECTION; PREVALENCE;
ADULTS; MORPHOLOGY; ANOMALIES; CHILDREN; DISEASE; WOMEN
AB Background Congenital aortic valve fusion is associated with aortic dilation, aneurysm, and rupture in girls and women with Turner syndrome. Our objective was to characterize aortic valve structure in subjects with Turner syndrome and to determine the prevalence of aortic dilation and valve dysfunction associated with different types of aortic valves.
Methods and Results The aortic valve and thoracic aorta were characterized by cardiovascular MRI in 208 subjects with Turner syndrome in an institutional review board-approved natural history study. Echocardiography was used to measure peak velocities across the aortic valve and the degree of aortic regurgitation. Four distinct valve morphologies were identified: tricuspid aortic valve, 64% (n=133); partially fused aortic valve, 12% (n=25); bicuspid aortic valve, 23% (n=47); and unicuspid aortic valve, 1% (n=3). Age and body surface area were similar in the 4 valve morphology groups. There was a significant trend, independent of age, toward larger body surface area-indexed ascending aortic diameters with increasing valve fusion. Ascending aortic diameters were (meanSD) 16.9 +/- 3.3, 18.3 +/- 3.3, and 19.8 +/- 3.9 mm/m(2) (P<0.0001) for tricuspid aortic valve, partially fused aortic valve, and bicuspid aortic valve+unicuspid aortic valve, respectively. Partially fused aortic valve, bicuspid aortic valve, and unicuspid aortic valve were significantly associated with mild aortic regurgitation and elevated peak velocities across the aortic valve.
Conclusions Aortic valve abnormalities in Turner syndrome occur with a spectrum of severity and are associated with aortic root dilation across age groups. Partial fusion of the aortic valve, traditionally regarded as an acquired valve problem, had an equal age distribution and was associated with an increased ascending aortic diameters.
C1 [Baba, Ridhwan Y.; Bakalov, Vladimir; Bondy, Carolyn A.] NICHHD, Bethesda, MD USA.
[Olivieri, Laura J.; Arai, Andrew E.; Bandettini, W. Patricia; Rosing, Douglas R.; Sachdev, Vandana] NHLBI, NIH, Bethesda, MD 20892 USA.
RP Olivieri, LJ (reprint author), NHLBI, NIH, Ctr Clin, Bldg 10,Room B1D416,MSC 1061, Bethesda, MD 20892 USA.
EM Laura.Olivieri@nih.gov
FU National Institutes of Health Division of Intramural Research at the
National Heart, Lung, and Blood Institute; Division of Intramural
Research at the National Institute of Child Health and Human Development
FX This work was supported by the National Institutes of Health Division of
Intramural Research at the National Heart, Lung, and Blood Institute, as
well as the Division of Intramural Research at the National Institute of
Child Health and Human Development.
NR 35
TC 14
Z9 15
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1941-9651
EI 1942-0080
J9 CIRC-CARDIOVASC IMAG
JI Circ.-Cardiovasc. Imaging
PD NOV
PY 2013
VL 6
IS 6
BP 1018
EP 1023
DI 10.1161/CIRCIMAGING.113.000526
PG 6
WC Cardiac & Cardiovascular Systems; Radiology, Nuclear Medicine & Medical
Imaging
SC Cardiovascular System & Cardiology; Radiology, Nuclear Medicine &
Medical Imaging
GA 253UI
UT WOS:000327114400029
PM 24084490
ER
PT J
AU Hong, CW
Xu, S
Imbesi, KL
Wood, BJ
AF Hong, Cheng William
Xu, Sheng
Imbesi, Kimberly L.
Wood, Bradford J.
TI Integrated laser-guided CT biopsy
SO CLINICAL IMAGING
LA English
DT Article
DE Biopsy; Angle selection; CT guidance; Interventional; Laser guidance
ID GUIDANCE-SYSTEM; NAVIGATION; DEVICE
AB The diagnostic yield of computed tomography (CT)-guided biopsies is dependent on accurate needle insertion. A laser-assisted angle selection system was custom fabricated and used during a CT-guided lung biopsy. Off-target error was measured comparing standard methods to the laser method while pointing towards the target from the skin. The difference between the planned angle and selected angle using the laser-assisted system was 2, improved from 12 with the standard method. Although yet to be confirmed, laser-assisted angle selection systems may improve the accuracy of needle placement, which may translate into improved outcomes for certain needle based procedures. Published by Elsevier Inc.
C1 [Hong, Cheng William; Xu, Sheng; Imbesi, Kimberly L.; Wood, Bradford J.] NIH, Ctr Intervent Oncol, Ctr Clin, Bethesda, MD 20892 USA.
[Hong, Cheng William] Cleveland Clin, Lerner Coll Med, Cleveland, OH 44195 USA.
[Imbesi, Kimberly L.] Duke Univ, Sch Med, Durham, NC 27705 USA.
RP Wood, BJ (reprint author), NIH, Ctr Intervent Oncol, Ctr Clin, 10 Ctr Dr MSC 1182, Bethesda, MD 20892 USA.
EM bwood@nih.gov
FU Intramural Research Program of the National Institutes of Health (NIH);
Center for Interventional Oncology; Pfizer Inc; Leona M. and Harry B.
Helmsley Charitable Trust; Howard Hughes Medical Institute
FX Thanks to Ankur Kapoor, PhD who assisted in software and hardware design
and custom integration. This study was supported in part by the
Intramural Research Program of the National Institutes of Health (NIH)
and the Center for Interventional Oncology. The opinions expressed
herein do not necessarily represent the opinions of the U.S. Government
or the NIH. This research was made possible through the NIH Medical
Research Scholars Program, a public-private partnership supported
jointly by the NIH and generous contributions to the Foundation for the
NIH from Pfizer Inc, The Leona M. and Harry B. Helmsley Charitable
Trust, and the Howard Hughes Medical Institute, as well as other private
donors. For a complete list, please visit the Foundation website at
http://www.
fnih.org/work/programs-development/medical-research-scholars- program.
NIH and Philips Healthcare have a cooperative research and development
agreement
NR 10
TC 4
Z9 4
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0899-7071
EI 1873-4499
J9 CLIN IMAG
JI Clin. Imaging
PD NOV-DEC
PY 2013
VL 37
IS 6
BP 1135
EP 1137
DI 10.1016/j.clinimag.2013.08.006
PG 3
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 250NE
UT WOS:000326858700030
PM 24035262
ER
PT J
AU Zheng, W
Thorne, N
McKew, JC
AF Zheng, Wei
Thorne, Natasha
McKew, John C.
TI Phenotypic screens as a renewed approach for drug discovery
SO DRUG DISCOVERY TODAY
LA English
DT Review
ID PLURIPOTENT STEM-CELLS; CHOLESTEROL ABSORPTION INHIBITOR;
CALCIUM-CHANNEL ANTAGONISTS; PARKINSONS-DISEASE; TARGETS;
IDENTIFICATION; MODULATORS; MECHANISM; TOXICITY; ASSAYS
AB The significant reduction in the number of newly approved drugs in the past decade has been partially attributed to failures in discovery and validation of new targets. Evaluation of recently approved new drugs has revealed that the number of approved drugs discovered through phenotypic screens, an original drug screening paradigm, has exceeded those discovered through the molecular target-based approach. Phenotypic screening is thus gaining new momentum in drug discovery with the hope that this approach may revitalize drug discovery and improve the success rate of drug approval through the discovery of viable lead compounds and identification of novel drug targets.
C1 [Zheng, Wei; Thorne, Natasha; McKew, John C.] NIH, Natl Ctr Adv Translat Sci, Bethesda, MD 20892 USA.
RP Zheng, W (reprint author), NIH, Natl Ctr Adv Translat Sci, 9800 Med Ctr Dr, Bethesda, MD 20892 USA.
EM wzheng@mail.nih.gov
RI Zheng, Wei/J-8889-2014
OI Zheng, Wei/0000-0003-1034-0757
FU Intramural Research Program of the National Center for Advancing
Translational Sciences, National Institutes of Health
FX This work was supported by the Intramural Research Program of the
National Center for Advancing Translational Sciences, National
Institutes of Health.
NR 82
TC 69
Z9 73
U1 7
U2 35
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 1359-6446
EI 1878-5832
J9 DRUG DISCOV TODAY
JI Drug Discov. Today
PD NOV
PY 2013
VL 18
IS 21-22
BP 1067
EP 1073
DI 10.1016/j.drudis.2013.07.001
PG 7
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 252JO
UT WOS:000327001200006
PM 23850704
ER
PT J
AU Jenkins, LMM
Figeys, D
AF Jenkins, Lisa M. Miller
Figeys, Daniel
TI Dynamic proteins: changes in structures, activities and networks
SO FEBS JOURNAL
LA English
DT Article
C1 [Jenkins, Lisa M. Miller] NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA.
[Figeys, Daniel] Univ Ottawa, Ottawa Inst Syst Biol, Dept Biochem & Microbiol & Immunol, Ottawa, ON K1N 6N5, Canada.
RP Jenkins, LMM (reprint author), NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 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 1742-464X
EI 1742-4658
J9 FEBS J
JI FEBS J.
PD NOV
PY 2013
VL 280
IS 22
BP 5569
EP 5569
DI 10.1111/febs.12548
PG 1
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 254AA
UT WOS:000327130900001
ER
PT J
AU Wlodawer, A
Minor, W
Dauter, Z
Jaskolski, M
AF Wlodawer, Alexander
Minor, Wladek
Dauter, Zbigniew
Jaskolski, Mariusz
TI Protein crystallography for aspiring crystallographers or how to avoid
pitfalls and traps in macromolecular structure determination
SO FEBS JOURNAL
LA English
DT Review
DE data collection and processing; electron density maps; protein
crystallography; structure refinement; structure solution; structure
quality; structure validation
ID HIGH-RESOLUTION STRUCTURE; X-RAY-STRUCTURE; NATIVE BIOLOGICAL
MACROMOLECULES; PANCREATIC TRYPSIN-INHIBITOR; NERVE GROWTH-FACTOR;
CRYSTAL-STRUCTURE; ANOMALOUS DIFFRACTION; MOLECULAR-REPLACEMENT;
3-DIMENSIONAL STRUCTURE; SYNCHROTRON-RADIATION
AB The number of macromolecular structures deposited in the Protein Data Bank now approaches 100000, with the vast majority of them determined by crystallographic methods. Thousands of papers describing such structures have been published in the scientific literature, and 20 Nobel Prizes in chemistry or medicine have been awarded for discoveries based on macromolecular crystallography. New hardware and software tools have made crystallography appear to be an almost routine (but still far from being analytical) technique and many structures are now being determined by scientists with very limited experience in the practical aspects of the field. However, this apparent ease is sometimes illusory and proper procedures need to be followed to maintain high standards of structure quality. In addition, many noncrystallographers may have problems with the critical evaluation and interpretation of structural results published in the scientific literature. The present review provides an outline of the technical aspects of crystallography for less experienced practitioners, as well as information that might be useful for users of macromolecular structures, aiming to show them how to interpret (but not overinterpret) the information present in the coordinate files and in their description. A discussion of the extent of information that can be gleaned from the atomic coordinates of structures solved at different resolution is provided, as well as problems and pitfalls encountered in structure determination and interpretation.
C1 [Wlodawer, Alexander] NCI, Prot Struct Sect, Macromol Crystallog Lab, Frederick, MD 21702 USA.
[Minor, Wladek] Univ Virginia, Dept Mol Physiol & Biol Phys, Charlottesville, VA USA.
[Minor, Wladek] Midwest Ctr Struct Genom, Lemont, IL USA.
[Minor, Wladek] New York Struct Genom Consortium, New York, NY USA.
[Minor, Wladek] Ctr Struct Genom Infect Dis, Bethesda, MD USA.
[Dauter, Zbigniew] NCI, Synchrotron Radiat Res Sect, Macromol Crystallog Lab, Argonne Natl Lab, Chicago, IL USA.
[Jaskolski, Mariusz] Adam Mickiewicz Univ, Fac Chem, Dept Crystallog, PL-60780 Poznan, Poland.
[Jaskolski, Mariusz] Polish Acad Sci, Inst Bioorgan Chem, Ctr Biocrystallog Res, Poznan, Poland.
RP Wlodawer, A (reprint author), NCI, Prot Struct Sect, Macromol Crystallog Lab, Frederick, MD 21702 USA.
EM wlodawer@nih.gov
RI Minor, Wladek/F-3096-2014;
OI Minor, Wladek/0000-0001-7075-7090
FU NIH, National Cancer Institute, Center for Cancer Research; Federal
funds from the National Institute of Allergy and Infectious Diseases,
National Institutes of Health, Department of Health and Human Services
[HHSN272201200026C]; [GM053163]; [GM094585]; [GM094662]; [GM093342]
FX We thank Dr Jerry Alexandratos for assistance with the preparation of
the figures and Milosz Ruszkowski for the photograph in Fig. 1A.
Original work in the laboratories of A. W. and Z.D. was supported by the
Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research. W. M. was supported by grants GM053163,
GM094585, GM094662 and GM093342, and was funded in part with Federal
funds from the National Institute of Allergy and Infectious Diseases,
National Institutes of Health, Department of Health and Human Services,
under Contract No. HHSN272201200026C.
NR 136
TC 27
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U1 3
U2 49
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 2013
VL 280
IS 22
BP 5705
EP 5736
DI 10.1111/febs.12495
PG 32
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 254AA
UT WOS:000327130900013
PM 24034303
ER
PT J
AU Bilke, S
Schwentner, R
Yang, F
Kauer, M
Jug, G
Walker, RL
Davis, S
Zhu, YLJ
Pineda, M
Meltzer, PS
Kovar, H
AF Bilke, Sven
Schwentner, Raphaela
Yang, Fan
Kauer, Maximilian
Jug, Gunhild
Walker, Robert L.
Davis, Sean
Zhu, Yuelin J.
Pineda, Marbin
Meltzer, Paul S.
Kovar, Heinrich
TI Oncogenic ETS fusions deregulate E2F3 target genes in Ewing sarcoma and
prostate cancer
SO GENOME RESEARCH
LA English
DT Article
ID TRANSCRIPTION FACTORS; RESPONSE ELEMENTS; CELLS; EWS-FLI1; TUMORS;
ACTIVATION; EXPRESSION; EWS/FLI-1; TRANSLOCATION; SPECIFICITY
AB Deregulated E2F transcription factor activity occurs in the vast majority of human tumors and has been solidly implicated in disturbances of cell cycle control, proliferation, and apoptosis. Aberrant E2F regulatory activity is often caused by impairment of control through pRB function, but little is known about the interplay of other oncoproteins with E2F. Here we show that ETS transcription factor fusions resulting from disease driving rearrangements in Ewing sarcoma (ES) and prostate cancer (PC) are one such class of oncoproteins. We performed an integrative study of genome-wide DNA-binding and transcription data in EWSR1/FLI1 expressing ES and TMPRSS2/ERG containing PC cells. Supported by promoter activity and mutation analyses, we demonstrate that a large fraction of E2F3 target genes are synergistically coregulated by these aberrant ETS proteins. We propose that the oncogenic effect of ETS fusion oncoproteins is in part mediated by the disruptive effect of the E2F-ETS interaction on cell cycle control. Additionally, a detailed analysis of the regulatory targets of the characteristic EWSR1/FLI1 fusion in ES identifies two functionally distinct gene sets. While synergistic regulation in concert with E2F in the promoter of target genes has a generally activating effect, EWSR1/FLI1 binding independent of E2F3 is predominantly associated with repressed differentiation genes. Thus, EWSR1/FLI1 appears to promote oncogenesis by simultaneously promoting cell proliferation and perturbing differentiation.
C1 [Bilke, Sven; Yang, Fan; Walker, Robert L.; Davis, Sean; Zhu, Yuelin J.; Pineda, Marbin; Meltzer, Paul S.] NCI, Genet Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Schwentner, Raphaela; Kauer, Maximilian; Jug, Gunhild; Kovar, Heinrich] St Anna Kinderkrebsforsch, Childrens Canc Res Inst, A-1090 Vienna, Austria.
[Kovar, Heinrich] Med Univ, Dept Pediat, A-1090 Vienna, Austria.
RP Meltzer, PS (reprint author), NCI, Genet Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
EM pmeltzer@mail.nih.gov
OI Kovar, Heinrich/0000-0001-6873-9109; Davis, Sean/0000-0002-8991-6458
FU Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research; Austrian Science Fund (FWF) [22328-B09]; 7th
Framework Program of the European Commission [259348]; Austrian Academy
of Sciences
FX This study was supported in part by the Intramural Research Program of
the NIH, National Cancer Institute, Center for Cancer Research and the
Austrian Science Fund (FWF), grant 22328-B09; and by the 7th Framework
Program of the European Commission, grant 259348 ("ASSET"). R.S. is a
recipient of a DOC-fFORTE scholarship of the Austrian Academy of
Sciences. We thank J. Waterfall for valuable discussions.
NR 42
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U2 6
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 2013
VL 23
IS 11
BP 1797
EP 1809
DI 10.1101/gr.151340.112
PG 13
WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Genetics & Heredity
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Genetics & Heredity
GA 247TA
UT WOS:000326642500004
PM 23940108
ER
PT J
AU Donato, M
Xu, ZH
Tomoiaga, A
Granneman, JG
MacKenzie, RG
Bao, RY
Than, NG
Westfall, PH
Romero, R
Draghici, S
AF Donato, Michele
Xu, Zhonghui
Tomoiaga, Alin
Granneman, James G.
MacKenzie, Robert G.
Bao, Riyue
Than, Nandor Gabor
Westfall, Peter H.
Romero, Roberto
Draghici, Sorin
TI Analysis and correction of crosstalk effects in pathway analysis
SO GENOME RESEARCH
LA English
DT Article
ID WHITE ADIPOSE-TISSUE; GENE-EXPRESSION; CELLULAR PLASTICITY; UTERINE
CERVIX; PARTURITION; PREGNANCY; IDENTIFICATION; TRANSCRIPTOME;
ACTIVATION; INDUCTION
AB Identifying the pathways that are significantly impacted in a given condition is a crucial step in understanding the underlying biological phenomena. All approaches currently available for this purpose calculate a P-value that aims to quantify the significance of the involvement of each pathway in the given phenotype. These P-values were previously thought to be independent. Here we show that this is not the case, and that many pathways can considerably affect each other's P-values through a "crosstalk" phenomenon. Although it is intuitive that various pathways could influence each other, the presence and extent of this phenomenon have not been rigorously studied and, most importantly, there is no currently available technique able to quantify the amount of such crosstalk. Here, we show that all three major categories of pathway analysis methods (enrichment analysis, functional class scoring, and topology-based methods) are severely influenced by crosstalk phenomena. Using real pathways and data, we show that in some cases pathways with significant P-values are not biologically meaningful, and that some biologically meaningful pathways with nonsignificant P-values become statistically significant when the crosstalk effects of other pathways are removed. We describe a technique able to detect, quantify, and correct crosstalk effects, as well as identify independent functional modules. We assessed this novel approach on data from four experiments involving three phenotypes and two species. This method is expected to allow a better understanding of individual experiment results, as well as a more refined definition of the existing signaling pathways for specific phenotypes.
C1 [Donato, Michele; Draghici, Sorin] Wayne State Univ, Dept Comp Sci, Detroit, MI 48084 USA.
[Xu, Zhonghui; Romero, Roberto] Wayne State Univ, Perinatol Res Branch, NICHD, NIH,Sch Med, Detroit, MI 48201 USA.
[Tomoiaga, Alin; Westfall, Peter H.] Texas Tech Univ, Ctr Adv Analyt & Business Intelligence, Lubbock, TX 79409 USA.
[Granneman, James G.; MacKenzie, Robert G.] Wayne State Univ, Ctr Integrat Metab & Endocrine Res, Detroit, MI 48084 USA.
[Bao, Riyue] Wayne State Univ, Dept Biol Sci, Detroit, MI 48084 USA.
[Than, Nandor Gabor] Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA.
[Draghici, Sorin] Wayne State Univ, Dept Clin & Translat Sci, Detroit, MI 48084 USA.
RP Draghici, S (reprint author), Wayne State Univ, Dept Comp Sci, Detroit, MI 48084 USA.
EM sorin@wayne.edu
RI Bao, Riyue/G-8765-2014;
OI Bao, Riyue/0000-0002-6105-1704; Draghici, Sorin/0000-0002-0786-8377
FU NIH [RO1 RDK089167, R42 GM087013]; NSF [DBI-0965741]; Robert J. Sokol
Endowment in Systems Biology; Perinatology Research Branch; Division of
Intramural Research, Eunice Kennedy Shriver National Institute of Child
Health and Human Development, NIH, DHH
FX This work has been partially supported by the following grants: NIH RO1
RDK089167, R42 GM087013, and NSF DBI-0965741 (to S. D.), by the Robert
J. Sokol Endowment in Systems Biology, and by the Perinatology Research
Branch, Division of Intramural Research, Eunice Kennedy Shriver National
Institute of Child Health and Human Development, NIH, DHHS. Any
opinions, findings, and conclusions or recommendations expressed in this
material are those of the authors and do not necessarily reflect the
views of the NSF, NIH, or any other of the funding agencies.
NR 29
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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 2013
VL 23
IS 11
BP 1885
EP 1893
DI 10.1101/gr.153551.112
PG 9
WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Genetics & Heredity
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology;
Genetics & Heredity
GA 247TA
UT WOS:000326642500012
PM 23934932
ER
PT J
AU Love, D
Keembiyehetty, C
Gavrilova, O
Comly, M
Harwood, K
Hanover, J
AF Love, Dona
Keembiyehetty, Chithra
Gavrilova, Oksana
Comly, Marcy
Harwood, Katryn
Hanover, John
TI A murine knockout of the human diabetes susceptibility locus Oga
contributes to acute and chronic nutrient sensing defects
SO GLYCOBIOLOGY
LA English
DT Meeting Abstract
CT Annual Conference of the Society-for-Glycobiology
CY NOV 17-20, 2013
CL St Petersburg, FL
SP Soc Glycobiol
C1 [Love, Dona; Keembiyehetty, Chithra; Gavrilova, Oksana; Comly, Marcy; Harwood, Katryn; Hanover, John] NIDDK, NIH, Bethesda, MD USA.
NR 0
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 0959-6658
EI 1460-2423
J9 GLYCOBIOLOGY
JI Glycobiology
PD NOV
PY 2013
VL 23
IS 11
MA 9
BP 1332
EP 1332
PG 1
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 251YY
UT WOS:000326972400019
ER
PT J
AU Zhang, LP
Ten Hagen, K
AF Zhang, Liping
Ten Hagen, Kelly
TI Mucin-type O-glycosylation is required for polarized secretion in the
Drosophila digestive system
SO GLYCOBIOLOGY
LA English
DT Meeting Abstract
CT Annual Conference of the Society-for-Glycobiology
CY NOV 17-20, 2013
CL St Petersburg, FL
SP Soc Glycobiol
C1 [Zhang, Liping; Ten Hagen, Kelly] 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 2013
VL 23
IS 11
MA 15
BP 1334
EP 1334
PG 1
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 251YY
UT WOS:000326972400025
ER
PT J
AU Akan, I
Love, D
Hanover, J
AF Akan, Ilhan
Love, Dona
Hanover, John
TI Deletion of Drosophila O-GlcNAcase (Oga) causes defects in oogenesis
SO GLYCOBIOLOGY
LA English
DT Meeting Abstract
CT Annual Conference of the Society-for-Glycobiology
CY NOV 17-20, 2013
CL St Petersburg, FL
SP Soc Glycobiol
C1 [Akan, Ilhan; Love, Dona; Hanover, John] NIDDK, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 3
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 2013
VL 23
IS 11
MA 101
BP 1365
EP 1365
PG 1
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 251YY
UT WOS:000326972400111
ER
PT J
AU Ichikawa, M
Scott, DA
Milner, JD
Su, H
Freeze, HH
AF Ichikawa, Mie
Scott, David A.
Milner, Joshua D.
Su, Helen
Freeze, Hudson H.
TI Hexosamine Metabolism in PGM3-Deficient Patient Fibroblasts
SO GLYCOBIOLOGY
LA English
DT Meeting Abstract
CT Annual Conference of the Society-for-Glycobiology
CY NOV 17-20, 2013
CL St Petersburg, FL
SP Soc Glycobiol
C1 [Ichikawa, Mie; Scott, David A.; Freeze, Hudson H.] Sanford Burnham Med Res Inst, La Jolla, CA USA.
[Milner, Joshua D.; Su, Helen] NIAID, NIH, Bethesda, MD 20892 USA.
RI Su, Helen/H-9541-2015
OI Su, Helen/0000-0002-5582-9110
NR 0
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 0959-6658
EI 1460-2423
J9 GLYCOBIOLOGY
JI Glycobiology
PD NOV
PY 2013
VL 23
IS 11
MA 140
BP 1378
EP 1378
PG 1
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 251YY
UT WOS:000326972400150
ER
PT J
AU Bond, M
Ghosh, S
Hanover, J
AF Bond, Michelle
Ghosh, Salil
Hanover, John
TI The nutrient sensor O-GlcNAc transferase is a critical component of the
C. elegans innate immune system
SO GLYCOBIOLOGY
LA English
DT Meeting Abstract
CT Annual Conference of the Society-for-Glycobiology
CY NOV 17-20, 2013
CL St Petersburg, FL
SP Soc Glycobiol
C1 [Bond, Michelle; Hanover, John] NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 1
U2 2
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 2013
VL 23
IS 11
MA 164
BP 1387
EP 1387
PG 1
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 251YY
UT WOS:000326972400174
ER
PT J
AU Harwood, K
Hanover, J
AF Harwood, Katryn
Hanover, John
TI The Enzymes of the O-GlcNAc Cycling: Writers AND Readers of the Histone
Code?
SO GLYCOBIOLOGY
LA English
DT Meeting Abstract
CT Annual Conference of the Society-for-Glycobiology
CY NOV 17-20, 2013
CL St Petersburg, FL
SP Soc Glycobiol
C1 [Harwood, Katryn; Hanover, John] NIDDK, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 2
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 2013
VL 23
IS 11
MA 165
BP 1387
EP 1387
PG 1
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 251YY
UT WOS:000326972400175
ER
PT J
AU Hanover, J
Bondy, C
Cheng, C
Bakalov, V
Zirzow, A
Olivier-Van Stichelen, S
Love, D
AF Hanover, John
Bondy, Carolyn
Cheng, Clara
Bakalov, Vladimir
Zirzow, Amanda
Olivier-Van Stichelen, Stephanie
Love, Dona
TI OGT is an X-linked imprinted gene linked to Cardiovascular Disease
Susceptibility
SO GLYCOBIOLOGY
LA English
DT Meeting Abstract
CT Annual Conference of the Society-for-Glycobiology
CY NOV 17-20, 2013
CL St Petersburg, FL
SP Soc Glycobiol
C1 [Hanover, John; Olivier-Van Stichelen, Stephanie; Love, Dona] NIDDK, NIH, Bethesda, MD 20892 USA.
[Bondy, Carolyn; Cheng, Clara; Bakalov, Vladimir] NICHD, Bethesda, MD USA.
[Zirzow, Amanda] Georgetown Univ, Washington, DC 20057 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0959-6658
EI 1460-2423
J9 GLYCOBIOLOGY
JI Glycobiology
PD NOV
PY 2013
VL 23
IS 11
MA 169
BP 1388
EP 1389
PG 2
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 251YY
UT WOS:000326972400179
ER
PT J
AU dos Santos, M
Duggal, R
Sacks, D
Beverley, S
AF dos Santos, Marcos
Duggal, Ryan
Sacks, David
Beverley, Stephen
TI Leishmania proteophosphoglycans (PPGs): genetic analysis of a parasite
mucin-like glycoprotein implicated in several key steps in the
infectious cycle
SO GLYCOBIOLOGY
LA English
DT Meeting Abstract
CT Annual Conference of the Society-for-Glycobiology
CY NOV 17-20, 2013
CL St Petersburg, FL
SP Soc Glycobiol
C1 [dos Santos, Marcos; Duggal, Ryan; Beverley, Stephen] Washington Univ, Sch Med, St Louis, MO 63130 USA.
[Sacks, David] 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 2013
VL 23
IS 11
MA 186
BP 1395
EP 1395
PG 1
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 251YY
UT WOS:000326972400196
ER
PT J
AU Saranummi, N
Spruijt-Metz, D
Intille, SS
Korhonen, I
Nilsen, WJ
Pavel, M
AF Saranummi, Niilo
Spruijt-Metz, Donna
Intille, Stephen S.
Korhonen, Ilkka
Nilsen, Wendy J.
Pavel, Misha
TI Moving the Science of Behavioral Change into the 21st Century: Part 2
SO IEEE PULSE
LA English
DT Article
C1 [Saranummi, Niilo] VTT Tech Res Ctr Finland, Tampere, Finland.
[Spruijt-Metz, Donna] Univ So Calif, Los Angeles, CA 90089 USA.
[Intille, Stephen S.; Pavel, Misha] Northeastern Univ, Boston, MA USA.
[Korhonen, Ilkka] Tampere Univ Technol, FIN-33101 Tampere, Finland.
[Nilsen, Wendy J.] US NIH, Off Behav & Social Sci Res, Bethesda, MD USA.
[Pavel, Misha] Natl Sci Fdn, Comp Informat Syst & Engn Dept, Arlington, VA USA.
RP Saranummi, N (reprint author), VTT Tech Res Ctr Finland, Tampere, Finland.
EM niilo.saranummi@vtt.fi; dmetz@usc.edu; S.Intille@neu.edu;
ilkka.korhonen@tut.fi; nilsenwj@od.nih.gov; mpavel@nsf.gov
RI Korhonen, Ilkka/G-4301-2014
OI Korhonen, Ilkka/0000-0002-5322-8469
NR 3
TC 0
Z9 0
U1 0
U2 1
PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC
PI PISCATAWAY
PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA
SN 2154-2287
J9 IEEE PULSE
JI IEEE Pulse
PD NOV-DEC
PY 2013
VL 4
IS 6
BP 32
EP 33
DI 10.1109/MPUL.2013.2279619
PG 2
WC Engineering, Biomedical
SC Engineering
GA 252DL
UT WOS:000326984900015
PM 24233189
ER
PT J
AU Berera, D
Zambon, M
AF Berera, Deeva
Zambon, Maria
TI Antivirals in the 2009 pandemic - lessons and implications for future
strategies
SO INFLUENZA AND OTHER RESPIRATORY VIRUSES
LA English
DT Article; Proceedings Paper
CT 2nd isirv Antiviral Group Conference on Severe Influenza-Burden,
Pathogenesis and Management
CY OCT 29-31, 2012
CL Hanoi, VIETNAM
DE 2009 Pandemic; antivirals; influenza
ID INFLUENZA-A H1N1; NEURAMINIDASE INHIBITOR TREATMENT; UNITED-KINGDOM;
OSELTAMIVIR; IMMUNIZATION; PROPHYLAXIS; CONTAINMENT; RESISTANCE;
MORTALITY; CHILDREN
AB The World Health Organization's declaration of an imminent swine-origin influenza A pandemic in April 2009 triggered the global launch of national pandemic preparedness plans. An integral component of pandemic preparedness in many countries was the targeted use of antiviral therapy for containment, disease mitigation, and treatment. The 2009 pandemic marked the first pandemic during which influenza antivirals were available for global use. Although most national pandemic plans included provisions for antiviral treatment, these pre-determined protocols required frequent updating as more information became available about the virus, and its susceptibility to antiviral agents, the epidemiology of infection, and the population groups that were most susceptible to severe disease. National public health agencies in countries with both plans for use of antivirals and pre-existing stockpiles, including those in Japan, the United Kingdom, and the United States, operated distinctly different antiviral distribution and treatment programs from one another. In the 3years following the pandemic, there is still little comparison of the diversity of national antiviral treatment policies and drug distribution mechanisms that were implemented, whether they had any mitigating effects and which might be most efficient. The purpose of this study is to outline roles of antiviral medicines in a pandemic period, provide insights into the diversity of antiviral treatment and distribution policies applied by selected countries between April 2009-July 2010, and to stimulate discussion on whether these policies remain appropriate for implementation in future pandemics.
C1 [Berera, Deeva] NIH, Div Int Epidemiol & Populat Studies, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Zambon, Maria] Publ Hlth England, Reference Microbiol Serv, Colindale, England.
RP Zambon, M (reprint author), Publ Hlth England, Reference Microbiol Serv, 61 Colindale Ave, London NW9 5EQ, England.
EM maria.zambon@phe.gov.uk
FU Influenza Research Program of the Division of International Epidemiology
and Population Studies, Fogarty International Center, National
Institutes of Health; International Influenza Unit, Office of Global
Affairs, Department of Health and Human Services, USA
FX DB received financial support from the Influenza Research Program of the
Division of International Epidemiology and Population Studies, Fogarty
International Center, National Institutes of Health, which is funded by
the International Influenza Unit, Office of Global Affairs, Department
of Health and Human Services, USA.
NR 36
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U1 0
U2 18
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1750-2640
EI 1750-2659
J9 INFLUENZA OTHER RESP
JI Influenza Other Respir. Viruses
PD NOV
PY 2013
VL 7
SU 3
SI SI
BP 72
EP 79
DI 10.1111/irv.12172
PG 8
WC Infectious Diseases; Virology
SC Infectious Diseases; Virology
GA 251VK
UT WOS:000326959200010
PM 24215385
ER
PT J
AU Ruffin, J
AF Ruffin, John
TI Translating Science into Better Health: The Power of Diversity and
Multicultural Engagement Preface
SO JOURNAL OF HEALTH CARE FOR THE POOR AND UNDERSERVED
LA English
DT Editorial Material
C1 NIMHD, Natl Inst Minor Hlth & Hlth Dispar, Res Ctr Minor Inst, RCMI Program, Bethesda, MD USA.
RP Ruffin, J (reprint author), NIMHD, Natl Inst Minor Hlth & Hlth Dispar, Res Ctr Minor Inst, RCMI Program, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU JOHNS HOPKINS UNIV PRESS
PI BALTIMORE
PA JOURNALS PUBLISHING DIVISION, 2715 NORTH CHARLES ST, BALTIMORE, MD
21218-4363 USA
SN 1049-2089
EI 1548-6869
J9 J HEALTH CARE POOR U
JI J. Health Care Poor Underserved
PD NOV
PY 2013
VL 24
IS 4
SU S
BP VIII
EP IX
PG 2
WC Health Policy & Services; Public, Environmental & Occupational Health
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health
GA 251CK
UT WOS:000326905200001
PM 24241270
ER
PT J
AU Fujioka, H
Phelix, CF
Friedland, RP
Zhu, XW
Perry, EA
Castellani, RJ
Perry, G
AF Fujioka, Hisashi
Phelix, Clyde F.
Friedland, Robert P.
Zhu, Xiongwei
Perry, Elizabeth A.
Castellani, Rudy J.
Perry, George
TI Alipoprotein E4 Prevents Growth of Malaria at the Intraerythrocyte
Stage: Implications For Differences in Racial Susceptibility to
Alzheimer's Disease
SO JOURNAL OF HEALTH CARE FOR THE POOR AND UNDERSERVED
LA English
DT Article; Proceedings Paper
CT 13th Research-Centers-in-Minority-Institutions (RCMI) International
Symposium on Health Disparities
CY DEC, 2012
CL Univ Cent Caribe, Ponce Sch Med, RCMI Programs, San Juan, PR
SP Res Ctr Minor Inst, Univ Cent Caribe, Ponce Sch Med & Hlth Sci, Univ Puerto Rico
HO Univ Cent Caribe, Ponce Sch Med, RCMI Programs
DE Aging; diet; evolution; health disparity; lipids; malaria
ID APOLIPOPROTEIN-E POLYMORPHISM; PLASMODIUM-FALCIPARUM; NATURAL-SELECTION;
AFRICA; POPULATIONS; CHLOROQUINE; DIAGNOSIS; PARASITES; DEMENTIA;
PROTEIN
AB ApolipoproteinE 4 (ApoE 4) has been linked to pathogenesis of Alzheimer's disease and has been suggested to be maintained through evolutionary pressure via a protective role in malaria infection. We evaluated Plasmodium falciparum viability at the intraerythrocyte stage by exposure to plasma from human subjects with ApoE 4/4 or ApoE 3/3. Plasma samples from ApoE 4/4 but not ApoE 3/3 donors inhibited growth and disrupted morphology of P. falciparum. Evolutionary history is characterized by war between pathogenic microorganisms and defense mechanisms countering their pathogenicities. ApoE 4 frequency is highest in sub-Saharan Africa and other isolated populations (e.g., Papua New Guinea) that exhibit endemic malaria. High ApoE frequency may offer selective advantage protecting against some infectious diseases (e.g., Plasmodium falciparum). These results implicate evolutionary pressure by malaria selecting humans with ApoE 4/4, even considering lower survival in late life. These selective advantages may be relevant in the exploration of possible disparities between Black and Whites in the incidence of Alzheimer's Disease.
C1 [Fujioka, Hisashi] Case Western Reserve Univ, Elect Microscopy Core Facil, Cleveland, OH 44106 USA.
[Phelix, Clyde F.] Univ Texas San Antonio, San Antonio, TX USA.
[Friedland, Robert P.] Univ Louisville, Sch Med, Dept Neurol, Louisville, KY 40292 USA.
[Friedland, Robert P.] Univ Louisville, Sch Med, Louisville, KY 40292 USA.
[Perry, Elizabeth A.] Natl Inst Dent, NIH, Washington, DC USA.
[Perry, Elizabeth A.] NIH, Craniofacial Res program, Washington, DC USA.
[Castellani, Rudy J.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA.
[Perry, George] Univ Texas San Antonio, Coll Sci, San Antonio, TX 78249 USA.
RP Perry, G (reprint author), Univ Texas San Antonio, Coll Sci, 1 UTSA Circle, San Antonio, TX 78249 USA.
EM george.perry@utsa.edu
RI Perry, Elizabeth/A-1628-2014; Perry, George/A-8611-2009; Friedland,
Robert/A-2834-2010; Phelix, Clyde/L-8048-2015
OI Perry, Elizabeth/0000-0001-9506-2578; Perry, George/0000-0002-6547-0172;
Friedland, Robert/0000-0001-5721-1843; Phelix, Clyde/0000-0002-6703-514X
FU NIAID NIH HHS [AI-058186-01, R03 AI058186]; NIMHD NIH HHS [G12 MD007591,
G12MD007591]
NR 40
TC 6
Z9 6
U1 2
U2 5
PU JOHNS HOPKINS UNIV PRESS
PI BALTIMORE
PA JOURNALS PUBLISHING DIVISION, 2715 NORTH CHARLES ST, BALTIMORE, MD
21218-4363 USA
SN 1049-2089
EI 1548-6869
J9 J HEALTH CARE POOR U
JI J. Health Care Poor Underserved
PD NOV
PY 2013
VL 24
IS 4
SU S
BP 70
EP 78
PG 9
WC Health Policy & Services; Public, Environmental & Occupational Health
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health
GA 251CK
UT WOS:000326905200011
PM 24241262
ER
PT J
AU Chaemsaithong, P
Madan, I
Romero, R
Than, NG
Tarca, AL
Draghici, S
Bhatti, G
Yeo, L
Mazor, M
Kim, CJ
Hassan, SS
Chaiworapongsa, T
AF Chaemsaithong, Piya
Madan, Ichchha
Romero, Roberto
Than, Nandor Gabor
Tarca, Adi L.
Draghici, Sorin
Bhatti, Gaurav
Yeo, Lami
Mazor, Moshe
Kim, Chong Jai
Hassan, Sonia S.
Chaiworapongsa, Tinnakorn
TI Characterization of the myometrial transcriptome in women with an arrest
of dilatation during labor
SO JOURNAL OF PERINATAL MEDICINE
LA English
DT Article
DE Angiopoietin-like 4 (ANGPTL4); arrest disorders; chemokine (C-C motif)
ligand 2 (CCL2); metallothionein (MT); myometrium; nitric oxide synthase
(NOS); pregnancy; parturition; systems biology; TGF signaling pathway;
transcriptomics
ID NITRIC-OXIDE SYNTHASE; CORTICOTROPIN-RELEASING HORMONE; UTERINE
SMOOTH-MUSCLE; PREGNANT HUMAN MYOMETRIUM; HUMAN-FETAL MEMBRANES;
METALLOTHIONEIN GENE-EXPRESSION; MONOCYTE CHEMOTACTIC PROTEIN-1;
ACTIVATED POTASSIUM CHANNEL; MESSENGER-RNA EXPRESSION; PROSTAGLANDIN-E
SYNTHASE
AB Objective: The molecular basis of failure to progress in labor is poorly understood. This study was undertaken to characterize the myometrial transcriptome of patients with an arrest of dilatation (AODIL).
Study design: Human myometrium was prospectively collected from women in the following groups: (1) spontaneous term labor (TL; n = 29) and (2) arrest of dilatation (AODIL; n = 14). Gene expression was characterized using Illumina (R) HumanHT-12 microarrays. A moderated Student's t-test and false discovery rate adjustment were used for analysis. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) of selected genes was performed in an independent sample set. Pathway ana-lysis was performed on the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway database using Pathway Analysis with Down-weighting of Overlapping Genes (PADOG). The MetaCore knowledge base was also searched for pathway analysis.
Results: (1) Forty-two differentially expressed genes were identified in women with an AODIL; (2) gene ontology analysis indicated enrichment of biological processes, which included regulation of angiogenesis, response to hypoxia, inflammatory response, and chemokine-mediated signaling pathway. Enriched molecular functions included transcription repressor activity, heat shock protein (Hsp) 90 binding, and nitric oxide synthase (NOS) activity; (3) MetaCore analysis identified immune response chemokine (C-C motif) ligand 2 (CCL2) signaling, muscle contraction regulation of endothelial nitric oxide synthase (eNOS) activity in endothelial cells, and triiodothyronine and thyroxine signaling as significantly overrepresented (false discovery rate <0.05); (4) qRT-PCR confirmed the overexpression of Nitric oxide synthase 3 (NOS3); hypoxic ischemic factor 1A (HIF1A); Chemokine (C-C motif) ligand 2 (CCL2); angiopoietin-like 4 (ANGPTL4); ADAM metallopeptidase with thrombospondin type 1, motif 9 (ADAMTS9); G protein-coupled receptor 4 (GPR4); metallothionein 1A (MT1A); MT2A; and selectin E (SELE) in an AODIL.
Conclusion: The myometrium of women with AODIL has a stereotypic transcriptome profile. This disorder has been associated with a pattern of gene expression involved in muscle contraction, an inflammatory response, and hypoxia. This is the first comprehensive and unbiased examination of the molecular basis of an AODIL.
C1 [Romero, Roberto] Wayne State Univ, Hutzel Womens Hosp, NICHD, NIH,DHHS,Perinatol Res Branch, Detroit, MI 48201 USA.
[Chaemsaithong, Piya; Madan, Ichchha; Than, Nandor Gabor; Tarca, Adi L.; Bhatti, Gaurav; Yeo, Lami; Hassan, Sonia S.; Chaiworapongsa, Tinnakorn] NICHD, NIH, DHHS, Perinatol Res Branch, Detroit, MI USA.
[Chaemsaithong, Piya; Madan, Ichchha; Than, Nandor Gabor; Yeo, Lami; Hassan, Sonia S.; Chaiworapongsa, Tinnakorn] Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI 48201 USA.
[Tarca, Adi L.; Draghici, Sorin] Wayne State Univ, Dept Comp Sci, Detroit, MI 48201 USA.
[Mazor, Moshe] Ben Gurion Univ Negev, Soroka Univ Med Ctr, Sch Med, Dept Obstet & Gynecol, Beer Sheva, Israel.
[Kim, Chong Jai] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Pathol, Seoul, South Korea.
RP Romero, R (reprint author), Wayne State Univ, Hutzel Womens Hosp, NICHD, NIH,DHHS,Perinatol Res Branch, 3990 John R,Box 4, Detroit, MI 48201 USA.
EM romeror@mail.nih.gov
OI Draghici, Sorin/0000-0002-0786-8377
FU Perinatology Research Branch, Division of Intramural Research, Eunice
Kennedy Shriver National Institute of Child Health and Human
Development, National Institutes of Health, Department of Health and
Human Services (NICHD/NIH); NICHD, NIH [HSN275201300006C]
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); and, in
part, with Federal funds from NICHD, NIH under Contract No.
HSN275201300006C. We wish to thank Dr. Susan Land and Dan Lott at the
Applied Genomics Technology Center of Wayne State University for
performing the microarrays and also acknowledge the contributions of the
nursing staff of the Perinatology Research Branch and Hutzel Women's
Hospital.
NR 203
TC 12
Z9 12
U1 0
U2 10
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 2013
VL 41
IS 6
BP 665
EP 681
DI 10.1515/jpm-2013-0086
PG 17
WC Obstetrics & Gynecology; Pediatrics
SC Obstetrics & Gynecology; Pediatrics
GA 252QO
UT WOS:000327023800007
PM 23893668
ER
PT J
AU Cardone, G
Heymann, JB
Steven, AC
AF Cardone, Giovanni
Heymann, J. Bernard
Steven, Alasdair C.
TI One number does not fit all: Mapping local variations in resolution in
cryo-EM reconstructions
SO JOURNAL OF STRUCTURAL BIOLOGY
LA English
DT Article
DE Resolution; Cryo-electron microscopy; Three-dimensional reconstruction;
Image heterogeneity; Masking; Short-space Fourier transform
ID TO-NOISE RATIO; PARTICLE ELECTRON CRYOMICROSCOPY; HEPATITIS-B-VIRUS;
MOLECULAR ARCHITECTURE; 26S PROTEASOME; BINDING; RIBOSOME; MICROSCOPY;
VISUALIZATION; MICROGRAPHS
AB The resolution of density maps from single particle analysis is usually measured in terms of the highest spatial frequency to which consistent information has been obtained. This calculation represents an average over the entire reconstructed volume. In practice, however, substantial local variations in resolution may occur, either from intrinsic properties of the specimen or for technical reasons such as a non-isotropic distribution of viewing orientations. To address this issue, we propose the use of a space-frequency representation, the short-space Fourier transform, to assess the quality of a density map, voxel-by-voxel, i.e. by local resolution mapping. In this approach, the experimental volume is divided into small subvolumes and the resolution determined for each of them. It is illustrated in applications both to model data and to experimental density maps. Regions with lower-than-average resolution may be mobile components or ones with incomplete occupancy or result from multiple conformational states. To improve the interpretability of reconstructions, we propose an adaptive filtering approach that reconciles the resolution to which individual features are calculated with the results of the local resolution map. Published by Elsevier Inc.
C1 [Cardone, Giovanni; Heymann, J. Bernard; Steven, Alasdair C.] Natl Inst Arthrit Musculoskeletal & Skin Dis, Struct Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Steven, AC (reprint author), NIH, Bldg 50,Room 1517,50 South Dr MSC 8025, Bethesda, MD 20892 USA.
EM stevena@mail.nih.gov
OI Heymann, Bernard/0000-0002-8872-5326
FU National Institute of Arthritis and Musculoskeletal and Skin Diseases
(NIAMS)
FX This work was supported by the Intramural Research Program of the
National Institute of Arthritis and Musculoskeletal and Skin Diseases
(NIAMS).
NR 50
TC 25
Z9 25
U1 1
U2 10
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1047-8477
EI 1095-8657
J9 J STRUCT BIOL
JI J. Struct. Biol.
PD NOV
PY 2013
VL 184
IS 2
BP 226
EP 236
DI 10.1016/j.jsb.2013.08.002
PG 11
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA 254MY
UT WOS:000327171000014
PM 23954653
ER
PT J
AU Mittapalli, RK
Liu, XL
Adkins, CE
Nounou, MI
Bohn, KA
Terrell, TB
Qhattal, HS
Geldenhuys, WJ
Palmieri, D
Steeg, PS
Smith, QR
Lockman, PR
AF Mittapalli, Rajendar K.
Liu, Xinli
Adkins, Chris E.
Nounou, Mohamed I.
Bohn, Kaci A.
Terrell, Tori B.
Qhattal, Hussaini S.
Geldenhuys, Werner J.
Palmieri, Diane
Steeg, Patricia S.
Smith, Quentin R.
Lockman, Paul R.
TI Paclitaxel-Hyaluronic NanoConjugates Prolong Overall Survival in a
Preclinical Brain Metastases of Breast Cancer Model
SO MOLECULAR CANCER THERAPEUTICS
LA English
DT Article
ID TARGETED DRUG-DELIVERY; CENTRAL-NERVOUS-SYSTEM; P-GLYCOPROTEIN;
STEM-CELLS; IN-VIVO; MULTIDRUG-RESISTANCE; ANTITUMOR-ACTIVITY;
ACID-PACLITAXEL; CD44 EXPRESSION; LIPID RAFTS
AB Brain (central nervous system; CNS) metastases pose a life-threatening problem for women with advanced metastatic breast cancer. It has recently been shown that the vasculature within preclinical brain metastasis model markedly restricts paclitaxel delivery in approximately 90% of CNS lesions. Therefore to improve efficacy, we have developed an ultra-small hyaluronic acid (HA) paclitaxel nanoconjugate (similar to 5 kDa) that can passively diffuse across the leaky blood-tumor barrier and then be taken up into cancer cells (MDA-MB-231Br) via CD44 receptor-mediated endocytocis. Using CD44 receptor-mediated endocytosis as an uptake mechanism, HA-paclitaxel was able to bypass p-glycoprotein-mediated efflux on the surface of the cancer cells. In vitro cytoxicity of the conjugate and free paclitaxel were similar in that they (i) both caused cell-cycle arrest in the G(2)-M phase, (ii) showed similar degrees of apoptosis induction (cleaved caspase), and (iii) had similar IC50 values when compared with paclitaxel in MTT assay. A preclinical model of brain metastases of breast cancer using intracardiac injections of Luc-2 transfected MDA-MB-231Br cells was used to evaluate in vivo efficacy of the nanoconjugate. The animals administered with HA-paclitaxel nanoconjugate had significantly longer overall survival compared with the control and the paclitaxel-treated group (P < 0.05). This study suggests that the small molecular weight HA-paclitaxel nanoconjugates can improve standard chemotherapeutic drug efficacy in a preclinical model of brain metastases of breast cancer. (C) 2013 AACR.
C1 [Mittapalli, Rajendar K.; Liu, Xinli; Adkins, Chris E.; Nounou, Mohamed I.; Bohn, Kaci A.; Terrell, Tori B.; Qhattal, Hussaini S.; Smith, Quentin R.; Lockman, Paul R.] Texas Tech Univ, Hlth Sci Ctr, Sch Pharm, Dept Pharmaceut Sci, Amarillo, TX 79106 USA.
[Geldenhuys, Werner J.] Northeast Ohio Med Univ, Coll Pharm, Dept Pharmaceut Sci, Rootstown, OH USA.
[Palmieri, Diane; Steeg, Patricia S.] NCI, Womens Canc Sect, Mol Pharmacol Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Lockman, PR (reprint author), Texas Tech Univ, Hlth Sci Ctr, Sch Pharm, Dept Pharmaceut Sci, 1406 S Coulter Dr, Amarillo, TX 79106 USA.
EM paul.lockman@ttuhsc.edu
RI Palmieri, Diane/B-4258-2015;
OI Ismail Nounou, Mohamed/0000-0002-8589-2700
FU Department of Defense, Breast Cancer Research Program [W81 XWH-062-0033]
FX Funding for this study was provided by the Department of Defense, Breast
Cancer Research Program, grant W81 XWH-062-0033 (P.S. Steeg, D.
Palmieri, Q.R. Smith, and P.R. Lockman).
NR 57
TC 28
Z9 28
U1 1
U2 21
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 2013
VL 12
IS 11
BP 2389
EP 2399
DI 10.1158/1535-7163.MCT-13-0132
PG 11
WC Oncology
SC Oncology
GA 250WB
UT WOS:000326886000010
PM 24002934
ER
PT J
AU Chen, JQ
Lee, JH
Herrmann, MA
Park, KS
Heldman, MR
Goldsmith, PK
Wang, Y
Giaccone, G
AF Chen, Jin-Qiu
Lee, Jih-Hsiang
Herrmann, Michelle A.
Park, Kang-Seo
Heldman, Madeleine R.
Goldsmith, Paul K.
Wang, Yisong
Giaccone, Giuseppe
TI Capillary Isoelectric-Focusing Immunoassays to Study Dynamic Oncoprotein
Phosphorylation and Drug Response to Targeted Therapies in Non-Small
Cell Lung Cancer
SO MOLECULAR CANCER THERAPEUTICS
LA English
DT Article
ID TYROSINE KINASE; INHIBITOR SENSITIVITY; 1ST-LINE TREATMENT;
MYELOID-LEUKEMIA; OPEN-LABEL; EGFR; CHEMOTHERAPY; TRIAL; ACTIVATION;
ERLOTINIB
AB Developing proteomic biomarkers is valuable for evaluating therapeutic effects of drugs and generating better treatment strategies. However, conventional protein analysis is often challenging due to inadequate sample size of clinical specimens, lack of assay reproducibility, accuracy, and sensitivity. A novel capillary isoelectricfocusing (IEF) immunoassay system (NanoPro) was used to study the dynamic phosphorylation status of signaling molecules in non-small cell lung cancer (NSCLC) cells treated with EGFR tyrosine kinase and MEK inhibitors. NanoPro showed the same dynamic ERK phosphorylation as Western blotting with good assay reproducibility using 1,000 times less protein. The IEF separation in NanoPro system enables multiple protein phosphorylation isoforms to be resolved and detected simultaneously. With NanoPro, we identified a specific on-target mitogen-activated protein/extracellular signal-regulated kinase (MEK) response pattern to MEK inhibitor PD325901, which was not detectable by Western blot analysis. We also revealed a MEK2 signal that may be associated with NSCLC cell sensitivity to the EGF receptor inhibitor erlotinib, and distinguished erlotinib-sensitive cells from intrinsic as well as acquired resistant cells to erlotinib. Moreover, NanoPro could differentiate human ERK1 isoforms from the mouse isoforms based on their isoelectric point differences and showed that erlotinib effectively inhibited ERK phosphorylation in targeted human xenograft cancer cells but not in surrounding mouse stromal cells. With 8 mu g of tumor aspirates, we precisely quantified the response of 18 signaling molecules to erlotinib and MEK1 inhibitor treatments in an NSCLC patient. NanoPro's higher sensitivity, better resolution of protein phosphorylation status, and reduced tissue requirement warrant NanoPro's investigation for future drug development and evaluation of drug effects of targeted therapies. Mol Cancer Ther; 12(11); 2601-13. (C) 2013 AACR.
C1 [Chen, Jin-Qiu; Herrmann, Michelle A.; Heldman, Madeleine R.] NCI, Collaborat Prot Technol Resource, Cell Biol Lab, NIH, Bethesda, MD 20892 USA.
[Lee, Jih-Hsiang; Park, Kang-Seo; Wang, Yisong; Giaccone, Giuseppe] NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Goldsmith, Paul K.] NCI, Off Sci & Technol Partnership, Off Director, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
RP Giaccone, G (reprint author), Georgetown Univ, 3970 Reservoir Rd NW, Washington, DC 20007 USA.
EM gg496@georgetown.edu
OI Giaccone, Giuseppe/0000-0002-5023-7562
FU Intramural Research Program, Center for Cancer Research, National Cancer
Institute, NIH
FX G. Giaccone was financially supported by the Intramural Research
Program, Center for Cancer Research, National Cancer Institute, NIH.
NR 35
TC 11
Z9 11
U1 0
U2 12
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 2013
VL 12
IS 11
BP 2601
EP 2613
DI 10.1158/1535-7163.MCT-13-0074
PG 13
WC Oncology
SC Oncology
GA 250WB
UT WOS:000326886000028
PM 23979919
ER
PT J
AU Mittleman, B
Neil, G
Cutcher-Gershenfeld, J
AF Mittleman, Barbara
Neil, Garry
Cutcher-Gershenfeld, Joel
TI Precompetitive consortia in biomedicine-how are we doing?
SO NATURE BIOTECHNOLOGY
LA English
DT Article
ID DRUG DISCOVERY; INNOVATION
C1 [Mittleman, Barbara] US NIH, Bethesda, MD 20892 USA.
[Neil, Garry] Johnson & Johnson, New Brunswick, NJ USA.
[Cutcher-Gershenfeld, Joel] Univ Illinois, Urbana, IL 61801 USA.
RP Mittleman, B (reprint author), Nodality, San Francisco, CA USA.
EM barbara.mittleman@nodality.com
NR 17
TC 3
Z9 3
U1 0
U2 6
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 2013
VL 31
IS 11
BP 979
EP 985
DI 10.1038/nbt.2731
PG 7
WC Biotechnology & Applied Microbiology
SC Biotechnology & Applied Microbiology
GA 251IM
UT WOS:000326921200015
PM 24213770
ER
PT J
AU Hinrichs, CS
Restifo, NP
AF Hinrichs, Christian S.
Restifo, Nicholas P.
TI Reassessing target antigens for adoptive T-cell therapy
SO NATURE BIOTECHNOLOGY
LA English
DT Review
ID TUMOR GENE WT1; PROSTATE-SPECIFIC ANTIGEN; COLONY-STIMULATING FACTOR;
CARBONIC-ANHYDRASE-IX; BREAST-CANCER CELLS; CARCINOEMBRYONIC ANTIGEN;
METASTATIC MELANOMA; NORMAL-TISSUES; TELOMERASE ACTIVITY;
MULTIPLE-MYELOMA
AB Adoptive T-cell therapy can target and kill widespread malignant cells thereby inducing durable clinical responses in melanoma and selected other malignances. However, many commonly targeted tumor antigens are also expressed by healthy tissues, and T cells do not distinguish between benign and malignant tissues if both express the target antigen. Autoimmune toxicity from T cell-mediated destruction of normal tissue has limited the development and adoption of this otherwise promising type of cancer therapy. A review of the unique biology of T-cell therapy and of recent clinical experience compels a reassessment of target antigens that traditionally have been viewed from the perspective of weaker immunotherapeutic modalities. It is important that target antigens chosen for adoptive T-cell therapy are expressed by tumors and not by essential healthy tissues. The risk of adverse autoimmune events can be further mitigated by generating antigen receptors using strategies that reduce the chance of cross-reactivity against epitopes in unintended targets. In general, a circumspect approach to target selection and thoughtful preclinical and clinical studies are pivotal to the ongoing advancement of these promising treatments.
C1 [Hinrichs, Christian S.; Restifo, Nicholas P.] NCI, Surg Branch, NIH, Bethesda, MD 20892 USA.
RP Restifo, NP (reprint author), NCI, Surg Branch, NIH, Bethesda, MD 20892 USA.
EM restifo@nih.gov
OI Restifo, Nicholas P./0000-0003-4229-4580
FU Intramural NIH HHS [ZIA BC010763-07]
NR 108
TC 47
Z9 48
U1 1
U2 25
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 2013
VL 31
IS 11
BP 999
EP 1008
DI 10.1038/nbt.2725
PG 10
WC Biotechnology & Applied Microbiology
SC Biotechnology & Applied Microbiology
GA 251IM
UT WOS:000326921200021
PM 24142051
ER
PT J
AU Wu, YC
Wawrzusin, P
Senseney, J
Fischer, RS
Christensen, R
Santella, A
York, AG
Winter, PW
Waterman, CM
Bao, ZR
Colon-Ramos, DA
McAuliffe, M
Shroff, H
AF Wu, Yicong
Wawrzusin, Peter
Senseney, Justin
Fischer, Robert S.
Christensen, Ryan
Santella, Anthony
York, Andrew G.
Winter, Peter W.
Waterman, Clare M.
Bao, Zhirong
Colon-Ramos, Daniel A.
McAuliffe, Matthew
Shroff, Hari
TI Spatially isotropic four-dimensional imaging with dual-view plane
illumination microscopy
SO NATURE BIOTECHNOLOGY
LA English
DT Article
ID LIGHT-SHEET MICROSCOPY; NEMATODE CAENORHABDITIS-ELEGANS; LIVING CELLS;
C-ELEGANS; IMPROVES RESOLUTION; DYNAMICS; 3D; SPECIMENS; EMBRYOS; LIVE
AB Optimal four-dimensional imaging requires high spatial resolution in all dimensions, high speed and minimal photobleaching and damage. We developed a dual-view, plane illumination microscope with improved spatiotemporal resolution by switching illumination and detection between two perpendicular objectives in an alternating duty cycle. Computationally fusing the resulting volumetric views provides an isotropic resolution of 330 nm. As the sample is stationary and only two views are required, we achieve an imaging speed of 200 images/s (i.e., 0.5 s for a 50-plane volume). Unlike spinning-disk confocal or Bessel beam methods, which illuminate the sample outside the focal plane, we maintain high spatiotemporal resolution over hundreds of volumes with negligible photobleaching. To illustrate the ability of our method to study biological systems that require high-speed volumetric visualization and/or low photobleaching, we describe microtubule tracking in live cells, nuclear imaging over 14 h during nematode embryogenesis and imaging of neural wiring during Caenorhabditis elegans brain development over 5 h.
C1 [Wu, Yicong; Wawrzusin, Peter; York, Andrew G.; Winter, Peter W.; Shroff, Hari] NIH, Sect High Resolut Opt Imaging, Natl Inst Biomed Imaging & Bioengn, Bethesda, MD 20892 USA.
[Senseney, Justin; McAuliffe, Matthew] NIH, Biomed Imaging Res Serv Sect, Ctr Informat Technol, Bethesda, MD 20892 USA.
[Fischer, Robert S.; Waterman, Clare M.] NHLBI, NIH, Bethesda, MD 20892 USA.
[Christensen, Ryan; Colon-Ramos, Daniel A.] Yale Univ, Sch Med, Program Cellular Neurosci Neurodegenerat & Repair, New Haven, CT USA.
[Christensen, Ryan; Colon-Ramos, Daniel A.] Yale Univ, Sch Med, Dept Cell Biol, New Haven, CT 06510 USA.
[Santella, Anthony; Bao, Zhirong] Mem Sloan Kettering Canc Ctr, Dev Biol Program, New York, NY 10021 USA.
RP Wu, YC (reprint author), NIH, Sect High Resolut Opt Imaging, Natl Inst Biomed Imaging & Bioengn, Bldg 10, Bethesda, MD 20892 USA.
EM yicong.wu@nih.gov
RI Shroff, Hari/E-7247-2016;
OI Shroff, Hari/0000-0003-3613-8215; Bao, Zhirong/0000-0002-2201-2745;
Waterman, Clare/0000-0001-6142-6775
FU National Institutes of Health (NIH) [GM097576, HD075602]; US National
Institutes of Health (NIH) [R01 NS076558, U01HD075602]; Intramural
Research Programs of the NIH National Institute of Biomedical Imaging
and Bioengineering; National Institute of Heart, Lung, and Blood; Center
for Information Technology
FX We thank J. McNally and C.-H. Lee for illuminating discussions, M. R.
Reinhardt for helping us with the scientific cMOS, W. Mohler for helping
us to share and view 4D data sets, G. Rondeau for help with mechanical
design, A.Hoofring for help with illustrations and H. Eden for critical
feedback on the manuscript. A.S. and Z.B. acknowledge funding from
National Institutes of Health (NIH) grants GM097576 and HD075602. R.C.
and D.C.-R. acknowledge funding from US National Institutes of Health
(NIH) grants R01 NS076558 and U01HD075602. This work was supported by
the Intramural Research Programs of the NIH National Institute of
Biomedical Imaging and Bioengineering, the National Institute of Heart,
Lung, and Blood, and the Center for Information Technology.
NR 47
TC 67
Z9 68
U1 3
U2 25
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 2013
VL 31
IS 11
BP 1032
EP +
DI 10.1038/nbt.2713
PG 10
WC Biotechnology & Applied Microbiology
SC Biotechnology & Applied Microbiology
GA 251IM
UT WOS:000326921200026
PM 24108093
ER
PT J
AU Levy, D
Jiang, M
Szklo, A
de Almeida, LM
Autran, M
Bloch, M
AF Levy, David
Jiang, Miao
Szklo, Andre
de Almeida, Liz Maria
Autran, Mariana
Bloch, Michele
TI Smoking and Adverse Maternal and Child Health Outcomes in Brazil
SO NICOTINE & TOBACCO RESEARCH
LA English
DT Review
ID LOW-BIRTH-WEIGHT; INFANT-DEATH-SYNDROME; RISK-FACTORS; LIVE BIRTHS;
DEVELOPING-COUNTRY; CIGARETTE-SMOKING; SOUTHERN BRAZIL; PRETERM BIRTHS;
PREGNANCY; PREVALENCE
AB Introduction: Numerous studies from high-income countries document the causal relationship between cigarette smoking during pregnancy and adverse maternal and child health (MCH) outcomes. Less research has been conducted in low-and middle-income countries, but a burgeoning literature can be found for Brazil.
Methods: We review Brazilian studies of the prevalence of maternal smoking, the relative risk of smoking-attributable adverse MCH outcomes, and present new estimates for these outcomes, using the attributable fraction method.
Results: We found that Brazilian studies of the relative risks of smoking-attributable adverse MCH outcomes were broadly consistent with previous reviews. Based on a comparison of maternal smoking over time, smoking during pregnancy has declined by about 50% over the last 20 years in Brazil. For 2008, we estimate that 5,352 cases of spontaneous abortion, 10,929 cases of preterm birth, 20,717 cases of low birth weight, and 29 cases of sudden infant death syndrome are attributable to maternal smoking. Between 1989 and 2008, the percent of smoking-attributable adverse MCH outcomes in Brazil was at least halved.
Conclusions: The results show that over a 20-year period, during which Brazil implemented numerous effective tobacco control measures, the country experienced a dramatic decrease in both maternal smoking prevalence and smoking-attributable adverse MCH outcomes. Countries that implement effective tobacco control measures can expect to reduce both maternal smoking and adverse MCH outcomes, thereby improving the public health.
C1 [Levy, David] Georgetown Univ, Lombardi Comprehens Canc Ctr, Dept Oncol, Washington, DC 20007 USA.
[Jiang, Miao] Harvey L Neiman Hlth Policy Inst, Reston, VA USA.
[Szklo, Andre; de Almeida, Liz Maria; Autran, Mariana] Brazilian Natl Canc Inst, Dept Epidemiol, Rio De Janeiro, Brazil.
[Bloch, Michele] NCI, Bethesda, MD 20892 USA.
RP Levy, D (reprint author), Georgetown Univ, Lombardi Comprehens Canc Ctr, 3300 Whitehaven St NW,Suite 4100, Washington, DC 20007 USA.
EM dl777@georgetown.edu
FU Tobacco Control Research Branch of the National Cancer Institute
[HHSN261201000043C]
FX The funding was in the form of a Scientific and Technical Support
Contract (#HHSN261201000043C) from the Tobacco Control Research Branch
of the National Cancer Institute.
NR 53
TC 9
Z9 10
U1 1
U2 7
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 1462-2203
EI 1469-994X
J9 NICOTINE TOB RES
JI Nicotine Tob. Res.
PD NOV
PY 2013
VL 15
IS 11
BP 1797
EP 1804
DI 10.1093/ntr/ntt073
PG 8
WC Substance Abuse; Public, Environmental & Occupational Health
SC Substance Abuse; Public, Environmental & Occupational Health
GA 252AY
UT WOS:000326977900001
PM 23873977
ER
PT J
AU Mason, H
DeRubeis, MB
Foster, JC
Taylor, JMG
Worden, FP
AF Mason, Heidi
DeRubeis, Mary Beth
Foster, Jared C.
Taylor, Jeremy M. G.
Worden, Francis P.
TI Outcomes Evaluation of a Weekly Nurse Practitioner-Managed Symptom
Management Clinic for Patients With Head and Neck Cancer Treated With
Chemoradiotherapy
SO ONCOLOGY NURSING FORUM
LA English
DT Article
ID QUALITY-OF-LIFE
AB Purpose/Objectives: To determine whether improved monitoring through close follow-up with a nurse practitioner (NP) could enhance treatment compliance and decrease frequency of hospitalizations.
Design: Retrospective chart review
Setting: An academic National Cancer Institute designated comprehensive cancer center.
Sample: 151 patients aged 45-65 years diagnosed with stage III or IV oropharyngeal cancer.
Methods: Patients were nonrandomized to one of two groups: a prechemotherapy clinic group and a weekly NP-led clinic group. After examination of descriptive statistics, multiple linear and logistic regressions were used to compare groups across patient outcomes.
Main Research Variables: Hospitalization, chemotherapy dose deviations, and chemotherapy treatment completion.
Findings: The average number of visits during traditional treatment was three and, after initiation of the NP-led clinic, the number was six. The hospitalization rate was 28% in the traditional clinic group compared to 12% in the NP-led group. The rate of chemotherapy dose deviations was 48% in the traditional clinic group compared to 6% in the NP-led clinic group. Forty-six percent of patients in the traditional clinic group received the full seven scheduled doses of chemotherapy compared to 90% of patients seen in the NP-led clinic group.
Conclusions: A weekly NP-led symptom management clinic reduces rates of hospitalization and chemotherapy dose deviations and increases chemotherapy completion in patients receiving intensive chemoradiotherapy for oropharyngeal cancer.
Implications for Nursing: Patients receiving chemoradiotherapy benefit from close monitoring for toxicities by NPs to successfully complete their treatment and avoid hospitalization.
Knowledge Translation: Early interventions to manage toxicities in patients with head and neck cancer can improve outcomes. NPs are in a key position to manage these toxicities and, when symptoms are controlled, costs are reduced.
C1 [Mason, Heidi; DeRubeis, Mary Beth; Taylor, Jeremy M. G.] Univ Michigan, Med Ctr, Ann Arbor, MI 48109 USA.
[Foster, Jared C.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biostat & Bioinformat Branch, Div Intramural Populat Hlth Res, Bethesda, MD USA.
[Worden, Francis P.] Univ Michigan Hlth Syst, Hematol Oncol Fellowship Program, Ann Arbor, MI USA.
RP Mason, H (reprint author), Univ Michigan, Med Ctr, Ann Arbor, MI 48109 USA.
EM derubeist@att.net
FU NCI NIH HHS [CA83654, T32 CA083654]
NR 11
TC 7
Z9 7
U1 1
U2 4
PU ONCOLOGY NURSING SOC
PI PITTSBURGH
PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA
SN 0190-535X
J9 ONCOL NURS FORUM
JI Oncol. Nurs. Forum
PD NOV
PY 2013
VL 40
IS 6
BP 581
EP 586
DI 10.1188/13.ONF.40-06AP
PG 6
WC Oncology; Nursing
SC Oncology; Nursing
GA 250IT
UT WOS:000326847100011
PM 24007925
ER
PT J
AU Biesecker, BB
Erby, LH
Woolford, S
Adcock, JY
Cohen, JS
Lamb, A
Lewis, KV
Truitt, M
Turriff, A
Reeve, BB
AF Biesecker, Barbara B.
Erby, Lori H.
Woolford, Samuel
Adcock, Jessica Young
Cohen, Julie S.
Lamb, Amanda
Lewis, Katie V.
Truitt, Megan
Turriff, Amy
Reeve, Bryce B.
TI Development and validation of the Psychological Adaptation Scale (PAS):
Use in six studies of adaptation to a health condition or risk
SO PATIENT EDUCATION AND COUNSELING
LA English
DT Article
DE Adaptation; The Psychological Adaptation Scale; Health threat of chronic
condition or risk; Outcomes of coping
ID ADJUSTMENT; STRESS; HOPE
AB Objective: We introduce The Psychological Adaptation Scale (PAS) for assessing adaptation to a chronic condition or risk and present validity data from six studies of genetic conditions.
Methods: Informed by theory, we identified four domains of adaptation: effective coping, self-esteem, social integration, and spiritual/existential meaning. Items were selected from the PROMIS "positive illness impact" item bank and adapted from the Rosenberg self-esteem scale to create a 20-item scale. Each domain included five items, with four sub-scale scores. Data from studies of six populations: adults affected with or at risk for genetic conditions (N = 3) and caregivers of children with genetic conditions (N = 3) were analyzed using confirmatory factor analyses (CFA).
Results: CFA suggested that all but five posited items converge on the domains as designed. Invariance of the PAS amongst the studies further suggested it is a valid and reliable tool to facilitate comparisons of adaptation across conditions.
Conclusion: Use of the PAS will standardize assessments of adaptation and foster understanding of the relationships among related health outcomes, such as quality of life and psychological well-being.
Practice implications: Clinical interventions can be designed based on PAS data to enhance dimensions of psychological adaptation to a chronic health condition or risk. Published by Elsevier Ireland Ltd.
C1 [Biesecker, Barbara B.] NHGRI, Social & Behav Res Branch, Bethesda, MD 20892 USA.
[Biesecker, Barbara B.; Erby, Lori H.] Johns Hopkins Bloomberg, Sch Publ Hlth, Hlth Behav & Soc, Baltimore, MD USA.
[Woolford, Samuel] Boston Univ, Boston, MA 02215 USA.
[Adcock, Jessica Young] Greater Baltimore Med Ctr, Baltimore, MD USA.
[Cohen, Julie S.; Lewis, Katie V.] NHGRI, Genet Dis Res Branch, Bethesda, MD 20892 USA.
[Lamb, Amanda] Maine Med Ctr Canc Inst, Portland, ME USA.
[Truitt, Megan] Columbia Univ, Med Ctr, New York, NY USA.
[Turriff, Amy] NEI, NIH, Bethesda, MD 20892 USA.
[Reeve, Bryce B.] Univ N Carolina, Chapel Hill, NC USA.
RP Biesecker, BB (reprint author), NHGRI, Social & Behav Res Branch, NIH, 31 Ctr Dr,MSC 2173, Bethesda, MD 20892 USA.
EM barbarab@mail.nih.gov
FU National Human Genome Research Institute Intramural Research Program,
National Institutes of Health
FX This research was funded by the National Human Genome Research Institute
Intramural Research Program, National Institutes of Health. We would
like to thank Sara Rosenbloom and Sophia Garcia from the PROMIS
consortium for their help in assessing psychometric performance of the
items.
NR 24
TC 10
Z9 10
U1 1
U2 8
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0738-3991
J9 PATIENT EDUC COUNS
JI Patient Educ. Couns.
PD NOV
PY 2013
VL 93
IS 2
BP 248
EP 254
DI 10.1016/j.pec.2013.05.006
PG 7
WC Public, Environmental & Occupational Health; Social Sciences,
Interdisciplinary
SC Public, Environmental & Occupational Health; Social Sciences - Other
Topics
GA 251CJ
UT WOS:000326905100012
PM 23993396
ER
PT J
AU Schnellbacher, C
Ciocca, G
Menendez, R
Aksentijevich, I
Goldbach-Mansky, R
Duarte, AM
Rivas-Chacon, R
AF Schnellbacher, Charlotte
Ciocca, Giovanna
Menendez, Roxanna
Aksentijevich, Ivona
Goldbach-Mansky, Raphaela
Duarte, Ana M.
Rivas-Chacon, Rafael
TI Deficiency of Interleukin-1 Receptor Antagonist Responsive to Anakinra
SO PEDIATRIC DERMATOLOGY
LA English
DT Article
ID AUTOINFLAMMATORY DISEASE
AB We describe a 3-month-old infant who presented to our institution with interleukin (IL)-1 receptor antagonist deficiency (DIRA), which consists of neutrophilic pustular dermatosis, periostitis, aseptic multifocal osteomyelitis, and persistently high acute-phase reactants. Skin findings promptly improved upon initiation of treatment with anakinra (recombinant human IL-1 receptor antagonist), and the bony lesions and systemic inflammation resolved with continued therapy.
C1 [Schnellbacher, Charlotte] Miami Childrens Hosp, Div Pediat, Miami, FL 33155 USA.
[Ciocca, Giovanna; Duarte, Ana M.] Miami Childrens Hosp, Div Dermatol, Miami, FL 33155 USA.
[Goldbach-Mansky, Raphaela] Miami Childrens Hosp, Div Rheumatol, Miami, FL 33155 USA.
[Menendez, Roxanna; Rivas-Chacon, Rafael] Nova SE Univ, Columbia Hosp, Div Dermatol, W Palm Beach, FL USA.
[Aksentijevich, Ivona] NIAMSD, NIH, Bethesda, MD 20892 USA.
RP Ciocca, G (reprint author), Miami Childrens Hosp, Div Dermatol, 3100 SW 62nd Ave, Miami, FL 33155 USA.
EM giovannaciocca@bellsouth.net
FU Intramural NIH HHS [ZIA AR041138-08]
NR 5
TC 10
Z9 10
U1 0
U2 0
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0736-8046
EI 1525-1470
J9 PEDIATR DERMATOL
JI Pediatr. Dermatol.
PD NOV
PY 2013
VL 30
IS 6
BP 758
EP 760
DI 10.1111/j.1525-1470.2012.01725.x
PG 3
WC Dermatology; Pediatrics
SC Dermatology; Pediatrics
GA 251YA
UT WOS:000326969100089
PM 22471702
ER
PT J
AU Firoz, EF
Turnbull, RK
Loomis, CA
Brownell, I
AF Firoz, Elnaz F.
Turnbull, Rowena K.
Loomis, Cynthia A.
Brownell, Isaac
TI Allergic Contact Dermatitis to Gamma-Irradiated WEBCOL Alcohol Prep Pads
SO PEDIATRIC DERMATOLOGY
LA English
DT Article
ID CHROMATOGRAPHY-MASS SPECTROMETRY; VOLATILE RADIOLYSIS PRODUCTS;
ISOPROPYL-ALCOHOL; DISINFECTANT SWAB
AB We report a case of allergic contact dermatitis to WEBCOL (R) alcohol prep pads in a healthy 17-year-old girl who showed no reaction to the individual components of the prep pads upon provocative use testing. Although several case reports have described allergic contact dermatitis to isopropyl alcohol, there have been no reports of allergic contact dermatitis to alcohol prep pads sterilized with gamma irradiation, a common sterilization technique capable of producing volatile products in this type of alcohol prep pad.
C1 [Firoz, Elnaz F.] Brown Univ, Rhode Isl Hosp, Dept Dermatol, Providence, RI 02903 USA.
[Turnbull, Rowena K.; Loomis, Cynthia A.] NYU, Sch Med, Dept Pathol, New York, NY USA.
[Brownell, Isaac] NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA.
RP Brownell, I (reprint author), NCI, Bldg 10 Magnuson Clin Ctr,Room 12N246,10 Ctr Dr, Bethesda, MD 20892 USA.
EM isaac.brownell@nih.gov
NR 14
TC 1
Z9 1
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0736-8046
EI 1525-1470
J9 PEDIATR DERMATOL
JI Pediatr. Dermatol.
PD NOV
PY 2013
VL 30
IS 6
BP E281
EP E282
DI 10.1111/j.1525-1470.2012.01727.x
PG 2
WC Dermatology; Pediatrics
SC Dermatology; Pediatrics
GA 251YA
UT WOS:000326969100058
PM 22471753
ER
PT J
AU Bjorge, T
Sorensen, HT
Grotmol, T
Engeland, A
Stephansson, O
Gissler, M
Tretli, S
Troisi, R
AF Bjorge, Tone
Sorensen, Henrik Toft
Grotmol, Tom
Engeland, Anders
Stephansson, Olof
Gissler, Mika
Tretli, Steinar
Troisi, Rebecca
TI Fetal Growth and Childhood Cancer: A Population-Based Study
SO PEDIATRICS
LA English
DT Article
DE birth weight; childhood cancer; fetal growth; nested case-control study;
Nordic countries
ID BIRTH-WEIGHT; GESTATIONAL-AGE; QUALITY-CONTROL; WILMS-TUMORS;
RISK-FACTORS; CNS TUMORS; CHILDREN; REGISTER; LEUKEMIA; NORWAY
AB OBJECTIVE: The etiology of childhood cancers is largely unknown. Studies have suggested that birth characteristics may be associated with risk. Our goal was to evaluate the risk of childhood cancers in relation to fetal growth.
METHODS: We conducted a case-control study nested within Nordic birth registries. The study included cancer cases diagnosed in Denmark, Finland, Norway, and Sweden among children born from 1967 to 2010 and up to 10 matched controls per case, totaling 17 698 cases and 172 422 controls. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were derived from conditional logistic regression.
RESULTS: Risks of all childhood cancers increased with increasing birth weight (P-trend <=.001). Risks of acute lymphoid leukemia and Wilms tumor were elevated when birth weight was >4000 g and of central nervous system tumors when birth weight was >4500 g. Newborns large for gestational age were at increased risk of Wilms tumor (OR: 2.1 [95% CI: 1.2-3.6]) and connective/soft tissue tumors (OR: 2.1 [95% CI: 1.1-4.4]). In contrast, the risk of acute myeloid leukemia was increased among children born small for gestational age (OR: 1.8 [95% CI: 1.1-3.1]). Children diagnosed with central nervous system tumors at,1 year of age had elevated risk with increasing head circumference (P-trend < .001). Those with head circumference >39 cm had the highest risk (OR: 4.7 [95% CI: 2.5-8.7]).
CONCLUSIONS: In this large, Nordic population-based study, increased risks for several childhood tumors were associated with measures of fetal growth, supporting the hypothesis that tumorigenesis manifesting in childhood is initiated in utero.
C1 [Bjorge, Tone; Engeland, Anders] Univ Bergen, Dept Global Publ Hlth & Primary Care, N-5020 Bergen, Norway.
[Bjorge, Tone; Engeland, Anders] Norwegian Inst Publ Hlth, Bergen, Norway.
[Sorensen, Henrik Toft] Aarhus Univ Hosp, Dept Clin Epidemiol, DK-8000 Aarhus, Denmark.
[Grotmol, Tom; Tretli, Steinar] Canc Registry Norway, Oslo, Norway.
[Stephansson, Olof] Karolinska Univ Hosp & Inst, Dept Med, Clin Epidemiol Unit, Stockholm, Sweden.
[Stephansson, Olof] Karolinska Univ Hosp & Inst, Div Obstet & Gynecol, Dept Women & Childrens Hlth, Stockholm, Sweden.
[Gissler, Mika] Natl Inst Hlth & Welf THL, Helsinki, Finland.
[Gissler, Mika] Nord Sch Publ Hlth NHV, Gothenburg, Sweden.
[Troisi, Rebecca] NCI, Div Canc Epidemiol, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Troisi, Rebecca] NCI, Div Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
RP Bjorge, T (reprint author), Univ Bergen, Dept Global Publ Hlth & Primary Care, N-5020 Bergen, Norway.
EM tone.bjorge@igs.uib.no
FU National Cancer Institute, National Institutes of Health, US Department
of Health and Human Services; National Institutes of Health (NIH)
FX This research was funded by the National Cancer Institute, National
Institutes of Health, US Department of Health and Human Services. Funded
by the National Institutes of Health (NIH).
NR 35
TC 12
Z9 13
U1 0
U2 3
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 2013
VL 132
IS 5
BP E1265
EP E1275
DI 10.1542/peds.2013-1317
PG 11
WC Pediatrics
SC Pediatrics
GA 245PE
UT WOS:000326475000018
PM 24167169
ER
PT J
AU Lionetti, G
Kimura, Y
Schanberg, LE
Beukelman, T
Wallace, CA
Ilowite, NT
Winsor, J
Fox, K
Natter, M
Sundy, JS
Brodsky, E
Curtis, JR
Del Gaizo, V
Iyasu, S
Jahreis, A
Meeker-O'Connell, A
Mittleman, BB
Murphy, BM
Peterson, ED
Raymond, SC
Setoguchi, S
Siegel, JN
Sobel, RE
Solomon, D
Southwood, TR
Vesely, R
White, PH
Wulffraat, NM
Sandborg, CI
AF Lionetti, Geraldina
Kimura, Yukiko
Schanberg, Laura E.
Beukelman, Timothy
Wallace, Carol A.
Ilowite, Norman T.
Winsor, Jane
Fox, Kathleen
Natter, Marc
Sundy, John S.
Brodsky, Eric
Curtis, Jeffrey R.
Del Gaizo, Vincent
Iyasu, Solomon
Jahreis, Angelika
Meeker-O'Connell, Ann
Mittleman, Barbara B.
Murphy, Bernard M.
Peterson, Eric D.
Raymond, Sandra C.
Setoguchi, Soko
Siegel, Jeffrey N.
Sobel, Rachel E.
Solomon, Daniel
Southwood, Taunton R.
Vesely, Richard
White, Patience H.
Wulffraat, Nico M.
Sandborg, Christy I.
TI Using Registries to Identify Adverse Events in Rheumatic Diseases
SO PEDIATRICS
LA English
DT Article
DE medication safety; immunomodulatory therapy; biologic products; juvenile
rheumatic disease
ID JUVENILE IDIOPATHIC ARTHRITIS; CROSS-SECTIONAL ANALYSIS; LONG-TERM
SAFETY; CHILDHOOD ARTHRITIS; CARRA REGISTRY; CHILDREN; ETANERCEPT;
METHOTREXATE; MALIGNANCY; DRUGS
AB The proven effectiveness of biologics and other immunomodulatory products in inflammatory rheumatic diseases has resulted in their widespread use as well as reports of potential short-and long-term complications such as infection and malignancy. These complications are especially worrisome in children who often have serial exposures to multiple immunomodulatory products. Post-marketing surveillance of immunomodulatory products in juvenile idiopathic arthritis (JIA) and pediatric systemic lupus erythematosus is currently based on product-specific registries and passive surveillance, which may not accurately reflect the safety risks for children owing to low numbers, poor long-term retention, and inadequate comparators. In collaboration with the US Food and Drug Administration (FDA), patient and family advocacy groups, biopharmaceutical industry representatives and other stakeholders, the Childhood Arthritis and Rheumatology Research Alliance (CARRA) and the Duke Clinical Research Institute (DCRI) have developed a novel pharmacosurveillance model (CARRA Consolidated Safety Registry [CoRe]) based on a multi-center longitudinal pediatric rheumatic diseases registry with over 8000 participants. The existing CARRA infrastructure provides access to much larger numbers of subjects than is feasible in single-product registries. Enrollment regardless of medication exposure allows more accurate detection and evaluation of safety signals. Flexibility built into the model allows the addition of specific data elements and safety outcomes, and designation of appropriate disease comparator groups relevant to each product, fulfilling post-marketing requirements and commitments. The proposed model can be applied to other pediatric and adult diseases, potentially transforming the paradigm of pharmacosurveillance in response to the growing public mandate for rigorous post-marketing safety monitoring.
C1 [Lionetti, Geraldina; Sandborg, Christy I.] Stanford Univ, Dept Pediat, Palo Alto, CA 94304 USA.
[Kimura, Yukiko] Hackensack Univ Med Ctr, Joseph M Sanzari Childrens Hosp, Dept Pediat, Hackensack, NJ 07601 USA.
[Schanberg, Laura E.] Duke Univ Med Ctr, Dept Pediat, Durham, NC USA.
[Beukelman, Timothy; Curtis, Jeffrey R.] Univ Alabama Birmingham, Dept Pediat, Birmingham, AL USA.
[Wallace, Carol A.] Seattle Childrens Hosp, Dept Pediat, Seattle, WA USA.
[Ilowite, Norman T.] Childrens Hosp Montefiore, Dept Pediat, Bronx, NY USA.
[Winsor, Jane; Fox, Kathleen; Sundy, John S.; Peterson, Eric D.; Setoguchi, Soko] Duke Clin Res Inst, Durham, NC USA.
[Natter, Marc] Boston Childrens Hosp, Dept Pediat, Boston, MA USA.
[Brodsky, Eric; Iyasu, Solomon; Meeker-O'Connell, Ann] US FDA, Silver Spring, MD USA.
[Del Gaizo, Vincent] Friends Childhood Arthrit & Rheumatol Res Allianc, Whitehouse Stn, NJ USA.
[Jahreis, Angelika; Siegel, Jeffrey N.] Genentech Inc, San Francisco, CA 94080 USA.
[Mittleman, Barbara B.] NIH, Bethesda, MD 20892 USA.
[Murphy, Bernard M.; White, Patience H.] Arthrit Fdn, Atlanta, GA USA.
[Raymond, Sandra C.] Lupus Fdn Amer, Washington, DC USA.
[Sobel, Rachel E.] Pfizer Inc, New York, NY USA.
[Solomon, Daniel] Brigham & Womens Hosp, Dept Rheumatol, Boston, MA 02115 USA.
[Southwood, Taunton R.] Univ Birmingham, Sch Immun & Infect, Birmingham, W Midlands, England.
[Vesely, Richard] European Med Agcy, London, England.
[Wulffraat, Nico M.] Univ Med Ctr Utrecht, Dept Pediat, Utrecht, Netherlands.
RP Kimura, Y (reprint author), Hackensack Univ Med Ctr, Joseph M Sanzari Childrens Hosp, 30 Prospect Ave, Hackensack, NJ 07601 USA.
EM YKimura@HackensackUMC.org
OI Sobel, Rachel/0000-0002-4492-9562
FU NIH [AR063890]; NIH ARRA [AR058934]; Arthritis Foundation; Friends of
CARRA; National Institutes of Health (NIH)
FX Supported in part by NIH grant AR063890 and NIH ARRA grant AR058934,
Arthritis Foundation, Friends of CARRA, and contributions from Abbott
Laboratories, Amgen, Inc, Bristol Myers Squibb Company, Genentech, Inc,
Human Genome Sciences, Inc, Novartis Pharmaceuticals, and Pfizer, Inc.
Funded by the National Institutes of Health (NIH).
NR 30
TC 6
Z9 6
U1 0
U2 6
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 2013
VL 132
IS 5
BP E1384
EP E1394
DI 10.1542/peds.2013-0755
PG 11
WC Pediatrics
SC Pediatrics
GA 245PE
UT WOS:000326475000030
PM 24144710
ER
PT J
AU Spergel, AR
Walkovich, K
Price, S
Niemela, JE
Wright, D
Fleisher, TA
Rao, VK
AF Spergel, Amanda Rudman
Walkovich, Kelly
Price, Susan
Niemela, Julie E.
Wright, Dowain
Fleisher, Thomas A.
Rao, V. Koneti
TI Autoimmune Lymphoproliferative Syndrome Misdiagnosed as Hemophagocytic
Lymphohistiocytosis
SO PEDIATRICS
LA English
DT Article
DE cytopenias; splenomegaly; lymphadenopathy; HLH; ALPS; apoptosis
ID SOMATIC FAS MUTATIONS; DIAGNOSIS; CHILDREN
AB Autoimmune lymphoproliferative syndrome (ALPS) is a rare inherited disorder of apoptosis, most commonly due to mutations in the FAS (TNFRSF6) gene. It presents with chronic lymphadenopathy, splenomegaly, and symptomatic multilineage cytopenias in an otherwise healthy child. Unfortunately, these clinical findings are also noted in other childhood lymphoproliferative conditions, such as leukemia, lymphoma, and hemophagocytic lymphohistiocytosis, which can confound the diagnosis. This report describes a 6-year-old girl with symptoms misdiagnosed as hemophagocytic lymphohistiocytosis and treated with chemotherapy before the recognition that her symptoms and laboratory values were consistent with a somatic FAS mutation leading to ALPS. This case should alert pediatricians to include ALPS in the differential diagnosis of a child with lymphadenopathy, splenomegaly, and cytopenias; obtain discriminating screening laboratory biomarkers, such as serum vitamin B-12 and ferritin levels; and, in the setting of a highly suspicious clinical scenario for ALPS, pursue testing for somatic FAS mutations when germ-line mutation testing is negative.
C1 [Spergel, Amanda Rudman; Price, Susan; Rao, V. Koneti] NIAID, ALPS Unit, Immunol Lab, Bethesda, MD 20892 USA.
[Niemela, Julie E.; Fleisher, Thomas A.] NIH, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA.
[Walkovich, Kelly] Univ Michigan, Div Pediat Hematol Oncol, Ann Arbor, MI 48109 USA.
[Wright, Dowain] Childrens Hosp Cent Calif, Div Rheumatol & Immunol, Madera, CA USA.
RP Rao, VK (reprint author), NIAID, ALPS Unit, LI, NIH,DHHS, Room 12C106,Bldg 10,10 Ctr Dr, Bethesda, MD 20892 USA.
EM krao@niaid.nih.gov
OI Niemela, Julie/0000-0003-4197-3792
FU Intramural Research Program of the National Institute of Allergy and
Infectious Diseases; National Institutes of Health Clinical Center;
National Institutes of Health (NIH)
FX The Intramural Research Program of the National Institute of Allergy and
Infectious Diseases and the National Institutes of Health Clinical
Center supported this research. Funded by the National Institutes of
Health (NIH).
NR 14
TC 9
Z9 9
U1 0
U2 3
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 2013
VL 132
IS 5
BP E1440
EP E1444
DI 10.1542/peds.2012-2748
PG 5
WC Pediatrics
SC Pediatrics
GA 245PE
UT WOS:000326475000038
ER
PT J
AU Hosgood, HD
Pao, W
Rothman, N
Hu, W
Pan, YH
Kuchinsky, K
Jones, KD
Xu, J
Vermeulen, R
Simko, J
Lan, Q
AF Hosgood, H. Dean, III
Pao, William
Rothman, Nathaniel
Hu, Wei
Pan, Yumei Helen
Kuchinsky, Kyle
Jones, Kirk D.
Xu, Jun
Vermeulen, Roel
Simko, Jeff
Lan, Qing
TI Driver mutations among never smoking female lung cancer tissues in China
identify unique EGFR and KRAS mutation pattern associated with household
coal burning
SO RESPIRATORY MEDICINE
LA English
DT Article
DE EGFR; KRAS; Lung cancer; Never smoking; China; Driver mutations
ID POLYCYCLIC AROMATIC-HYDROCARBONS; MAMMARY-CARCINOMA CELLS; FACTOR
RECEPTOR GENE; XUAN-WEI; COMBUSTION EMISSIONS; SOMATIC MUTATIONS;
EXPOSURE; SMOKERS; WOMEN; ADENOCARCINOMA
AB Lung cancer in never smokers, which has been partially attributed to household solid fuel use (i.e., coal), is etiologically and clinically different from lung cancer attributed to tobacco smoking. To explore the spectrum of driver mutations among lung cancer tissues from never smokers, specifically in a population where high lung cancer rates have been attributed to indoor air pollution from domestic coal use, multiplexed assays were used to detect >40 point mutations, insertions, and deletions (EGFR, KRAS, BRAF, HER2, NRAS, PIK3CA, MEK1, AKT1, and PTEN) among the lung tumors of confirmed never smoking females from Xuanwei, China [32 adenocarcinomas (ADCs), 7 squamous cell carcinomas (SCCs), 1 adenosquamous carcinoma (ADSC)]. EGFR mutations were detected in 35% of tumors. 46% of these involved EGFR exon 18 G719X, while 14% were exon 21 L858R mutations. KRAS mutations, all of which were G12C_34G>T, were observed in 15% of tumors. EGFR and KRAS mutations were mutually exclusive, and no mutations were observed in the other tested genes. Most point mutations were transversions and were also found in tumors from patients who used coal in their homes. Our high mutation frequencies in EGFR exon 18 and KRAS and low mutation frequency in EGFR exon 21 are strikingly divergent from those in other smoking and never smoking populations from Asia. Given that our subjects live in a region where coal is typically burned indoors, our findings provide new insights into the pathogenesis of lung cancer among never smoking females exposed to indoor air pollution from coal. (C) 2013 Elsevier Ltd. All rights reserved.
C1 [Hosgood, H. Dean, III; Rothman, Nathaniel; Hu, Wei; Lan, Qing] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD 20892 USA.
[Hosgood, H. Dean, III] Albert Einstein Coll Med, Div Epidemiol, Bronx, NY 10461 USA.
[Pao, William; Pan, Yumei Helen] Vanderbilt Ingram Canc Ctr, Dept Med, Nashville, TN USA.
[Kuchinsky, Kyle; Jones, Kirk D.; Simko, Jeff] Univ Calif San Francisco, Dept Anat Pathol, San Francisco, CA 94143 USA.
[Xu, Jun] Univ Hong Kong, Sch Publ Hlth, Dept Community Med, Hong Kong, Hong Kong, Peoples R China.
[Vermeulen, Roel] Univ Utrecht, Utrecht, Netherlands.
RP Hosgood, HD (reprint author), Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Div Epidemiol, 1300 Morris Pk Ave,Belfer 1309, Bronx, NY 10461 USA.
EM dean.hosgood@einstein.yu.edu
RI Hu, Wei/M-3524-2013; Vermeulen, Roel/F-8037-2011
OI Vermeulen, Roel/0000-0003-4082-8163
FU The Intramural National Cancer Institute program [N01-CO-12400];
[R01-CA121210]
FX Funding: The Intramural National Cancer Institute (N01-CO-12400) program
funded the work. WP was also funded through R01-CA121210.
NR 36
TC 6
Z9 7
U1 0
U2 18
PU W B SAUNDERS CO LTD
PI LONDON
PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND
SN 0954-6111
EI 1532-3064
J9 RESP MED
JI Respir. Med.
PD NOV
PY 2013
VL 107
IS 11
BP 1755
EP 1762
DI 10.1016/j.rmed.2013.08.018
PG 8
WC Cardiac & Cardiovascular Systems; Respiratory System
SC Cardiovascular System & Cardiology; Respiratory System
GA 255HU
UT WOS:000327230800014
PM 24055406
ER
PT J
AU Weir, CH
Yeatts, KB
Sarnat, JA
Vizuete, W
Salo, PM
Jaramillo, R
Cohn, RD
Chu, HT
Zeldin, DC
London, SJ
AF Weir, Charles H.
Yeatts, Karin B.
Sarnat, Jeremy A.
Vizuete, William
Salo, Paivi M.
Jaramillo, Renee
Cohn, Richard D.
Chu, Haitao
Zeldin, Darryl C.
London, Stephanie J.
TI Nitrogen dioxide and allergic sensitization in the 2005-2006 National
Health and Nutrition Examination Survey
SO RESPIRATORY MEDICINE
LA English
DT Article
DE Air pollution; Allergic; Sensitization; Epidemiology; NHANES; IgE
ID LONG-TERM EXPOSURE; AIR-POLLUTION; RESPIRATORY SYMPTOMS; CHILDREN;
ASTHMA; ATOPY; SCHOOLCHILDREN; POPULATION; POLLUTANTS; RESPONSES
AB Background: Allergic sensitization is a risk factor for asthma and allergic diseases. The relationship between ambient air pollution and allergic sensitization is unclear.
Objective: To investigate the relationship between ambient air pollution and allergic sensitization in a nationally representative sample of the US population.
Methods: We linked annual average concentrations of nitrogen dioxide (NO2), particulate matter <= 10 mu m (PM10), particulate matter <= 2.5 mu m (PM2.5), and summer concentrations of ozone (03), to allergen-specific immunoglobulin E (IgE) data for participants in the 2005-2006 National Health and Nutrition Examination Survey (NHANES). In addition to the monitor-based air pollution estimates, we used the Community Multiscale Air Quality (CMAQ) model to increase the representation of rural participants in our sample. Logistic regression with population-based sampling weights was used to calculate adjusted prevalence odds ratios per 10 ppb increase in O-3 and NO2, per 10 mu g/m(3) increase in PM10, and per 5 mu g/m(3) increase in PM2.5 adjusting for race, gender, age, socioeconomic status, smoking, and urban/rural status.
Results: Using CMAQ data, increased levels of NO2 were associated with positive IgE to any (OR 1.15, 95% CI 1.04, 1.27), inhalant (OR 1.17, 95% CI 1.02, 1.33), and indoor (OR 1.16, 95% CI 1.03, 1.31) allergens. Higher PM2.5 levels were associated with positivity to indoor allergen-specific IgE (OR 1.24, 95% CI 1.13, 1.36). Effect estimates were similar using monitored data.
Conclusions: Increased ambient NO2 was consistently associated with increased prevalence of allergic sensitization. (C) 2013 Elsevier Ltd. All rights reserved.
C1 [Weir, Charles H.; Vizuete, William] Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Environm Sci & Engn, Chapel Hill, NC USA.
[Yeatts, Karin B.] Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Epidemiol, Chapel Hill, NC 27515 USA.
[Sarnat, Jeremy A.] Emory Univ, Rollins Sch Publ Hlth, Dept Environm Hlth, Atlanta, GA 30322 USA.
[Salo, Paivi M.; Zeldin, Darryl C.] NIEHS, Div Intramural Res, NIH, Res Triangle Pk, NC 27709 USA.
[Jaramillo, Renee; Cohn, Richard D.] SRA Int Inc, Durham, NC USA.
[Chu, Haitao] Univ Minnesota, Sch Publ Hlth, Div Biostat, Minneapolis, MN 55455 USA.
[London, Stephanie J.] NIEHS, Epidemiol Branch, NIH, US Dept HHS, Res Triangle Pk, NC 27709 USA.
RP Yeatts, KB (reprint author), Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Epidemiol, Chapel Hill, NC 27515 USA.
EM Karin_Yeatts@unc.edu
RI Mashamba-Thompson, Tivani /B-6087-2014;
OI Chu, Haitao/0000-0003-0932-598X; vizuete, william/0000-0002-1399-2948;
London, Stephanie/0000-0003-4911-5290
FU Division of Health Studies Agency for Toxic Substances and Disease
Registry; Division of Intramural Research, National Institute of
Environmental Health Sciences, NIH, DHHS
FX This research was supported in part by Division of Health Studies Agency
for Toxic Substances and Disease Registry, and the Division of
Intramural Research, National Institute of Environmental Health
Sciences, NIH, DHHS. The findings and conclusions in this article are
those of the authors and do not represent the views of the National
Center for Environmental Health/Agency for Toxic Substances and Disease
Registry or National Institute of Environmental Health Sciences.
NR 49
TC 9
Z9 9
U1 1
U2 21
PU W B SAUNDERS CO LTD
PI LONDON
PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND
SN 0954-6111
EI 1532-3064
J9 RESP MED
JI Respir. Med.
PD NOV
PY 2013
VL 107
IS 11
BP 1763
EP 1772
DI 10.1016/j.rmed.2013.08.010
PG 10
WC Cardiac & Cardiovascular Systems; Respiratory System
SC Cardiovascular System & Cardiology; Respiratory System
GA 255HU
UT WOS:000327230800015
PM 24045117
ER
PT J
AU Rosansky, SJ
Cancarini, G
Clark, WF
Eggers, P
Germaine, M
Glassock, R
Goldfarb, DS
Harris, D
Hwang, SJ
Imperial, EB
Johansen, KL
Kalantar-Zadeh, K
Moist, LM
Rayner, B
Steiner, R
Zuo, L
AF Rosansky, Steven J.
Cancarini, Giovanni
Clark, William F.
Eggers, Paul
Germaine, Michael
Glassock, Richard
Goldfarb, David S.
Harris, David
Hwang, Shang-Jyh
Imperial, Edwina Brown
Johansen, Kirsten L.
Kalantar-Zadeh, Kamyar
Moist, Louise M.
Rayner, Brian
Steiner, Robert
Zuo, Li
TI Dialysis Initiation: What's the Rush?
SO SEMINARS IN DIALYSIS
LA English
DT Article
ID CHRONIC KIDNEY-DISEASE; STAGE RENAL-DISEASE; QUALITY-OF-LIFE; NATIONAL
COOPERATIVE DIALYSIS; HEMODIALYSIS-PATIENTS; PERITONEAL-DIALYSIS;
MAINTENANCE HEMODIALYSIS; NUTRITIONAL PARAMETERS; STARTING DIALYSIS;
MEMBRANE FLUX
AB The recent trend to early initiation of dialysis (at eGFR >10ml/min/1.73m(2)) appears to have been based on conventional wisdoms that are not supported by evidence. Observational studies using administrative databases report worse comorbidity-adjusted dialysis survival with early dialysis initiation. Although some have concluded that the IDEAL randomized controlled trial of dialysis start provided evidence that patients become symptomatic with late dialysis start, there is no definitive support for this view. The potential harms of early start of dialysis, including the loss of residual renal function (RRF), have been well documented. The rate of RRF loss (renal function trajectory) is an important consideration for the timing of the dialysis initiation decision. Patients with low glomerular filtration rate (GFR) may have sufficient RRF to be maintained off dialysis for years. Delay of dialysis start until a working arterio-venous access is in place seems prudent in light of the lack of harm and possible benefit of late dialysis initiation. Prescribing frequent hemodialysis is not recommended when dialysis is initiated early. The benefits of early initiation of chronic dialysis after episodes of congestive heart failure or acute kidney injury require further study. There are no data to show that early start benefits diabetics or other patient groups. Preemptive start of dialysis in noncompliant patients may be necessary to avoid complications. The decision to initiate dialysis requires informed patient consent and a joint decision by the patient and dialysis provider. Possible talking points for obtaining informed consent are provided.
C1 [Rosansky, Steven J.] Univ SC, Sch Publ Hlth, WJBDVA Hosp, Dorn Res Inst, Columbia, SC USA.
[Cancarini, Giovanni] AO Spedali Civili, OU Nephrol, Brescia, Italy.
[Cancarini, Giovanni] Univ Brescia, Brescia, Italy.
[Clark, William F.] Western Univ Canada, London Hlth Sci Ctr, London, ON, Canada.
[Eggers, Paul] NIDDK, Bethesda, MD 20892 USA.
[Germaine, Michael] Tufts Univ, Sch Med, Baystate Med Ctr, Springfield, MA 01199 USA.
[Glassock, Richard] Univ Calif Los Angeles, David Geffen Sch Med, Dept Med, Los Angeles, CA 90095 USA.
[Goldfarb, David S.] New York Harbor VA Healthcare Syst, Langone Med Ctr, Nephrol Sect, New York, NY USA.
[Goldfarb, David S.] NYU, New York, NY USA.
[Harris, David] Univ Sydney, Westmead Millennium Inst, Sydney, Australia.
[Hwang, Shang-Jyh] Kaohsiung Med Univ, Kaohsiung Med Univ Hosp, Div Nephrol, Kaohsiung, Taiwan.
[Imperial, Edwina Brown] Hammersmith Hosp, Renal & Transplant Ctr, London, England.
[Johansen, Kirsten L.] Univ Calif San Francisco, San Francisco VA Med Ctr, Div Nephrol, San Francisco, CA 94143 USA.
[Johansen, Kirsten L.] Nephrol Sect, San Francisco, CA USA.
[Kalantar-Zadeh, Kamyar] Univ Calif Irvine, Sch Med, UC Irvine Med Ctr, Div Nephrol & Hypertens, Irvine, CA USA.
[Moist, Louise M.] Univ Western Ontario, Schulich Sch Med & Dent, London Hlth Sci Ctr, Kidney Clin Res Unit, London, ON, Canada.
[Rayner, Brian] Groote Schuur Hosp, Div Nephrol & Hypertens, ZA-7925 Cape Town, South Africa.
[Rayner, Brian] Univ Cape Town, ZA-7925 Cape Town, South Africa.
[Steiner, Robert] Univ Calif San Diego, San Diego Med Ctr, San Diego, CA 92103 USA.
[Zuo, Li] Peking Univ, Hosp 1, Inst Nephrol, Renal Div,Key Lab,Minist Hlth, Beijing, Peoples R China.
RP Rosansky, SJ (reprint author), Dorn Res Inst, 526 N Trenholm Rd, Columbia, SC 29206 USA.
EM sjrcra@yahoo.com
OI Rayner, Brian/0000-0002-0167-9591; Kalantar-Zadeh,
Kamyar/0000-0002-8666-0725; Goldfarb, David/0000-0002-9215-1273
NR 73
TC 15
Z9 15
U1 0
U2 9
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0894-0959
EI 1525-139X
J9 SEMIN DIALYSIS
JI Semin. Dial.
PD NOV
PY 2013
VL 26
IS 6
BP 650
EP 657
DI 10.1111/sdi.12134
PG 8
WC Urology & Nephrology
SC Urology & Nephrology
GA 252SK
UT WOS:000327030200005
PM 24066675
ER
PT J
AU Cohen, SD
Kimmel, PL
AF Cohen, Scott D.
Kimmel, Paul L.
TI Quality of Life and Mental Health Related to Timing, Frequency and Dose
of Hemodialysis
SO SEMINARS IN DIALYSIS
LA English
DT Article
ID STAGE RENAL-DISEASE; DIALYSIS PATIENTS; BEHAVIORAL COMPLIANCE;
MAINTENANCE DIALYSIS; PSYCHOSOCIAL FACTORS; PRACTICE PATTERNS;
DEPRESSION; ADJUSTMENT; DIAGNOSIS; OUTCOMES
AB The perceived quality of life (QOL) and mental health of dialysis patients can have a significant impact on clinical outcomes in the end-stage renal disease (ESRD) population. There is growing interest in increasing dialysis frequency, dose and duration to achieve more adequate dialysis clearance, particularly of middle molecules. Over the past decade, there has been an interest in earlier initiation of dialysis; however, the results of the IDEAL study call this practice into question, and showed no difference in QOL scores between the early-start and later start dialysis patients. There are inconsistent results regarding the impact of increased dialysis frequency and dose on patients' perceived health-related QOL (HRQOL). Some studies of daily nocturnal dialysis patients show a positive impact on QOL, while others show no significant difference. The disparate outcomes may be partly related to differences in the demographic characteristics of the study populations and the specific questionnaires used to measure HRQOL. Additional research is necessary to determine whether changes in dialysis frequency, timing, and dose can positively or negatively impact patients' perceptions of their QOL and mental health.
C1 [Cohen, Scott D.; Kimmel, Paul L.] George Washington Univ, Div Renal Dis & Hypertens, Washington, DC 20037 USA.
[Kimmel, Paul L.] Natl Inst Diabet & Digest & Kidney Dis, Div Kidney Urol & Hematol Dis, Washington, DC USA.
RP Cohen, SD (reprint author), George Washington Univ, Med Fac Associates, Div Renal Dis & Hypertens, 2150 Penn Ave,Suite 3-438, Washington, DC 20037 USA.
EM scohen@mfa.gwu.edu
NR 40
TC 1
Z9 1
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0894-0959
EI 1525-139X
J9 SEMIN DIALYSIS
JI Semin. Dial.
PD NOV
PY 2013
VL 26
IS 6
BP 697
EP 701
DI 10.1111/sdi.12124
PG 5
WC Urology & Nephrology
SC Urology & Nephrology
GA 252SK
UT WOS:000327030200011
PM 24067246
ER
PT J
AU Beach, SR
Chen, DT
Huffman, JC
AF Beach, Scott Richard
Chen, Donna T.
Huffman, Jeff C.
TI Attitudes and Beliefs of Trainees and Nurses Regarding Delirium in the
Intensive Care Unit
SO ACADEMIC PSYCHIATRY
LA English
DT Editorial Material
ID CONFUSION ASSESSMENT METHOD; EDUCATION; PROFESSIONALS; KNOWLEDGE; ICU
C1 [Beach, Scott Richard; Huffman, Jeff C.] Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
[Chen, Donna T.] NIH, Dept Clin Bioeth, Bethesda, MD 20892 USA.
RP Beach, SR (reprint author), Massachusetts Gen Hosp, Dept Psychiat, Boston, MA 02114 USA.
EM sbeach1@partners.org
NR 15
TC 1
Z9 1
U1 3
U2 11
PU AMER PSYCHIATRIC PUBLISHING, INC
PI ARLINGTON
PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA
SN 1042-9670
EI 1545-7230
J9 ACAD PSYCHIATR
JI Acad. Psych.
PD NOV-DEC
PY 2013
VL 37
IS 6
BP 436
EP 438
PG 3
WC Education & Educational Research; Psychiatry
SC Education & Educational Research; Psychiatry
GA 246TH
UT WOS:000326561500017
PM 24185295
ER
PT J
AU Simmler, C
Fronczek, FR
Pauli, GF
Santarsiero, BD
AF Simmler, Charlotte
Fronczek, Frank R.
Pauli, Guido F.
Santarsiero, Bernard D.
TI Absolute configuration of naturally occurring glabridin
SO ACTA CRYSTALLOGRAPHICA SECTION C-CRYSTAL STRUCTURE COMMUNICATIONS
LA English
DT Article
DE crystal structure; absolute configuration; glabridin; natural compounds
ID LICORICE ROOT; GLYCYRRHIZA-GLABRA; ISOFLAVAN; (+/-)-GLABRIDIN;
FLAVONOIDS; AVERAGES
AB The title compound {systematic name: 4-[(3R)-8,8-dimethyl-3,4-dihydro-2H-pyrano[2,3-f]chromen-3-yl]benzene-1,3-diol, commonly named glabridin}, C20H20O4, is a species-specific biomarker from the roots Glycyrrhiza glabra L. (European licorice, Fabaceae). In the present study, this prenylated isoflavan has been purified from an enriched CHCl3 fraction of the extract of the root, using three steps of medium-pressure liquid chromatography (MPLC) by employing HW-40F, Sephadex LH-20 and LiChroCN as adsorbents. Pure glabridin was crystallized from an MeOH-H2O mixture (95:5v/v) to yield colorless crystals containing one molecule per asymmetric unit (Z = 1) in the space group P212121. Although the crystal structure has been reported before, the determination of the absolute configuration remained uncertain. Stereochemical analysis, including circular dichroism, NMR data and an X-ray diffraction data set with Bijvoet differences, confirms that glabridin, purified from its natural source, is found only in a C3 R configuration. These results can therefore be used as a reference for the assignment of the configuration and enantiopurity of any isolated or synthetic glabridin sample.
C1 [Simmler, Charlotte; Pauli, Guido F.; Santarsiero, Bernard D.] Univ Illinois, Coll Pharm, Dept Med Chem & Pharmacognosy, Chicago, IL 60612 USA.
[Simmler, Charlotte; Pauli, Guido F.] Univ Illinois, Coll Pharm, NIH, Ctr Bot Dietary Supplements Res, Chicago, IL 60612 USA.
[Fronczek, Frank R.] Louisiana State Univ, Dept Chem, Baton Rouge, LA 70803 USA.
[Santarsiero, Bernard D.] Univ Illinois, Coll Pharm, Ctr Pharmaceut Biotechnol, Chicago, IL 60607 USA.
RP Santarsiero, BD (reprint author), Univ Illinois, Coll Pharm, Ctr Pharmaceut Biotechnol, MC-870,900 S Ashland Ave, Chicago, IL 60607 USA.
EM bds@uic.edu
OI Pauli, Guido/0000-0003-1022-4326; Simmler, Charlotte/0000-0002-6923-2630
FU NCCAM; ODS [P50 AT000155]; US Department of Energy, Office of Science,
Office of Basic Energy Sciences [DE-AC02-06CH11357];
[LEQSF(2011-12)-ENH-TR-01]
FX This research was supported by NCCAM and ODS through grant No. P50
AT000155. The authors acknowledge use of the Life Sciences Collaborative
Access Team (LS-CAT) beamline 21-ID-D for the initial data collection;
use of the Advanced Photon Source at Argonne National Laboratory was
supported by the US Department of Energy, Office of Science, Office of
Basic Energy Sciences, under Contract No. DE-AC02-06CH11357. Upgrade of
the diffractometer was made possible by grant No.
LEQSF(2011-12)-ENH-TR-01, administered by the Louisiana Board of
Regents. Finally, we thank Dr Jose Napolitano, UIC Chicago (Illinois),
and Matthias Niemitz, Perch Solutions Ltd, Kuopio (Finland), for helpful
NMR discussions and PERCH support.
NR 30
TC 0
Z9 0
U1 1
U2 9
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0108-2701
EI 1600-5759
J9 ACTA CRYSTALLOGR C
JI Acta Crystallogr. Sect. C-Cryst. Struct. Commun.
PD NOV
PY 2013
VL 69
SI SI
BP 1212
EP +
DI 10.1107/S0108270113018842
PN 11
PG 12
WC Chemistry, Multidisciplinary; Crystallography
SC Chemistry; Crystallography
GA 247VR
UT WOS:000326651300003
PM 24192160
ER
PT J
AU Olsson, AC
Xu, YW
Schuz, J
Vlaanderen, J
Kromhout, H
Vermeulen, R
Peters, S
Stucker, I
Guida, F
Bruske, I
Wichmann, HE
Consonni, D
Landi, MT
Caporaso, N
Tse, LA
Yu, ITS
Siemiatycki, J
Richardson, L
Mirabelli, D
Richiardi, L
Simonato, L
Gustavsson, P
Plato, N
Jockel, KH
Ahrens, W
Pohlabeln, H
Tardon, A
Zaridze, D
Marcus, MW
't Mannetje, A
Pearce, N
McLaughlin, J
Demers, P
Szeszenia-Dabrowska, N
Lissowska, J
Rudnai, P
Fabianova, E
Dumitru, RS
Bencko, V
Foretova, L
Janout, V
Boffetta, P
Fortes, C
Bueno-de-Mesquita, B
Kendzia, B
Behrens, T
Pesch, B
Bruning, T
Straif, K
AF Olsson, Ann C.
Xu, Yiwen
Schuez, Joachim
Vlaanderen, Jelle
Kromhout, Hans
Vermeulen, Roel
Peters, Susan
Stuecker, Isabelle
Guida, Florence
Brueske, Irene
Wichmann, Heinz-Erich
Consonni, Dario
Landi, Maria Teresa
Caporaso, Neil
Tse, Lap Ah
Yu, Ignatius Tak-sun
Siemiatycki, Jack
Richardson, Lesley
Mirabelli, Dario
Richiardi, Lorenzo
Simonato, Lorenzo
Gustavsson, Per
Plato, Nils
Joeckel, Karl-Heinz
Ahrens, Wolfgang
Pohlabeln, Hermann
Tardon, Adonina
Zaridze, David
Marcus, Michael W.
't Mannetje, Andrea
Pearce, Neil
McLaughlin, John
Demers, Paul
Szeszenia-Dabrowska, Neonila
Lissowska, Jolanta
Rudnai, Peter
Fabianova, Eleonora
Dumitru, Rodica Stanescu
Bencko, Vladimir
Foretova, Lenka
Janout, Vladimir
Boffetta, Paolo
Fortes, Cristina
Bueno-de-Mesquita, Bas
Kendzia, Benjamin
Behrens, Thomas
Pesch, Beate
Bruning, Thomas
Straif, Kurt
TI Lung Cancer Risk Among Hairdressers: A Pooled Analysis of Case-Control
Studies Conducted Between 1985 and 2010
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE case-control studies; hair bleaching agents; hair color; lung neoplasms;
occupational exposure
ID DNA-REPAIR GENES; OCCUPATIONAL-EXPOSURE; CASE-REFERENT; POPULATION;
GERMANY; EUROPE; MEN; POLYMORPHISMS; CONSORTIUM; DISEASES
AB Increased lung cancer risks among hairdressers were observed in large registry-based cohort studies from Scandinavia, but these studies could not adjust for smoking. Our objective was to evaluate the lung cancer risk among hairdressers while adjusting for smoking and other confounders in a pooled database of 16 case-control studies conducted in Europe, Canada, China, and New Zealand between 1985 and 2010 (the Pooled Analysis of Case-Control Studies on the Joint Effects of Occupational Carcinogens in the Development of Lung Cancer). Lifetime occupational and smoking information was collected through interviews with 19,369 cases of lung cancer and 23,674 matched population or hospital controls. Overall, 170 cases and 167 controls had ever worked as hairdresser or barber. The odds ratios for lung cancer in women were 1.65 (95 confidence interval (CI): 1.16, 2.35) without adjustment for smoking and 1.12 (95 CI: 0.75, 1.68) with adjustment for smoking; however, women employed before 1954 also experienced an increased lung cancer risk after adjustment for smoking (odds ratio 2.66, 95 CI: 1.09, 6.47). The odds ratios in male hairdressers/barbers were generally not elevated, except for an increased odds ratio for adenocarcinoma in long-term barbers (odds ratio 2.20, 95 CI: 1.02, 4.77). Our results suggest that the increased lung cancer risks among hairdressers are due to their smoking behavior; single elevated risk estimates should be interpreted with caution and need replication in other studies.
C1 [Olsson, Ann C.; Xu, Yiwen; Schuez, Joachim; Vlaanderen, Jelle; Straif, Kurt] Int Agcy Res Canc, F-69372 Lyon, France.
[Olsson, Ann C.; Gustavsson, Per; Plato, Nils] Karolinska Inst, Inst Environm Med, S-10401 Stockholm, Sweden.
[Kromhout, Hans; Vermeulen, Roel; Peters, Susan] Inst Risk Assessment Sci, Utrecht, Netherlands.
[Peters, Susan] Western Australian Inst Med Res, Perth, WA, Australia.
[Stuecker, Isabelle; Guida, Florence] INSERM, Ctr Res Epidemiol & Populat Hlth CESP, Environm Epidemiol Canc Team, U1018, F-94807 Villejuif, France.
[Stuecker, Isabelle; Guida, Florence] Univ Paris Sud, UMRS 1018, F-94807 Villejuif, France.
[Brueske, Irene; Wichmann, Heinz-Erich] Inst Epidemiol I, Deutsch Forschungszentrum Gesundheit & Umwelt, Neuherberg, Germany.
[Consonni, Dario] Osped Maggiore Policlin, Fdn Ist Ricovero & Cura Carattere Sci IRCCS CaGra, Epidemiol Unit, Milan, Italy.
[Landi, Maria Teresa; Caporaso, Neil] NCI, Bethesda, MD 20892 USA.
[Tse, Lap Ah; Yu, Ignatius Tak-sun] Chinese Univ Hong Kong, Sch Publ Hlth & Primary Care, Div Occupat & Environm Hlth, Hong Kong, Hong Kong, Peoples R China.
[Siemiatycki, Jack; Richardson, Lesley] Univ Montreal, Hosp Res Ctr CRCHUM, Montreal, PQ, Canada.
[Consonni, Dario; Richiardi, Lorenzo] Univ Turin, Canc Epidemiol Unit, Dept Med Sci, Turin, Italy.
[Simonato, Lorenzo] Univ Padua, Dept Environm Med & Publ Hlth, Padua, Italy.
[Joeckel, Karl-Heinz] Univ Duisburg Essen, Inst Med Informat Biometry & Epidemiol, Essen, Germany.
[Ahrens, Wolfgang; Pohlabeln, Hermann] Bremen Inst Prevent Res & Social Med, Bremen, Germany.
[Tardon, Adonina] Univ Oviedo, Ctr Biomed Res, Network Epidemiol & Publ Hlth CIBERESP, Oviedo, Spain.
[Zaridze, David] Russian Canc Res Ctr, Moscow, Russia.
[Marcus, Michael W.] Univ Liverpool, Canc Res Ctr, Roy Castle Lung Canc Res Programme, Liverpool L69 3BX, Merseyside, England.
['t Mannetje, Andrea; Pearce, Neil] Massey Univ, Ctr Publ Hlth Res, Wellington, New Zealand.
[McLaughlin, John; Demers, Paul] Occupat Canc Res Ctr, Toronto, ON, Canada.
[Szeszenia-Dabrowska, Neonila] Nofer Inst Occupat Med, Lodz, Poland.
[Lissowska, Jolanta] M Sklodowska Curie Canc Ctr, Warsaw, Poland.
[Lissowska, Jolanta] Inst Oncol, Warsaw, Poland.
[Rudnai, Peter] Natl Inst Environm Hlth, Budapest, Hungary.
[Fabianova, Eleonora] Reg Author Publ Hlth, Banska Bystrica, Slovakia.
[Dumitru, Rodica Stanescu] Inst Publ Hlth, Bucharest, Romania.
[Bencko, Vladimir] Charles Univ Prague, Inst Hyg & Epidemiol, Fac Med 1, Prague, Czech Republic.
[Foretova, Lenka] Masaryk Mem Canc Inst, Brno, Czech Republic.
[Janout, Vladimir] Palacky Univ, Fac Med, CR-77147 Olomouc, Czech Republic.
[Boffetta, Paolo] Mt Sinai Sch Med, Tisch Canc Inst, New York, NY USA.
[Boffetta, Paolo] Int Prevent Res Inst, Lyon, France.
[Fortes, Cristina] IRCCS, IDI, Clin Epidemiol Unit, Rome, Italy.
[Bueno-de-Mesquita, Bas] Natl Inst Publ Hlth & Environm Protect RIVM, Bilthoven, Netherlands.
[Kendzia, Benjamin; Behrens, Thomas; Pesch, Beate; Bruning, Thomas] Ruhr Univ Bochum IPA, Inst Prevent & Occupat Med, German Social Accid Insurance Inst, Bochum, Germany.
RP Olsson, AC (reprint author), Int Agcy Res Canc, Environm & Radiat Sect, 150 Cours Albert Thomas, F-69372 Lyon 08, France.
EM olssona@iarc.fr
RI Bruske, Irene/N-3125-2013; Yu, Ignatius Tak Sun/A-9936-2008; Janout,
Vladimir/M-5133-2014; Szeszenia-Dabrowska, Neonila/F-7190-2010; Bruning,
Thomas/G-8120-2015; Consonni, Dario/K-7943-2016; Vermeulen,
Roel/F-8037-2011;
OI Ahrens, Wolfgang/0000-0003-3777-570X; Bruning,
Thomas/0000-0001-9560-5464; Consonni, Dario/0000-0002-8935-3843;
Vermeulen, Roel/0000-0003-4082-8163; Pearce, Neil/0000-0002-9938-7852;
Peters, Susan/0000-0001-5662-1971; richiardi,
lorenzo/0000-0003-0316-9402
FU German Social Accident Insurance (DGUV); Canadian Institutes for Health
Research; Guzzo-SRC Chair in Environment and Cancer; National Cancer
Institute of Canada; Canadian Cancer Society; Workplace Safety and
Insurance Board; Cancer Care Ontario; French Agency of Health Security
(ANSES); Fondation de France; French National Research Agency (ANR);
National Institute of Cancer (INCA); Fondation for Medical Research
(FRM); French Institute for Public Health Surveillance (InVS); Health
Ministry (DGS); Organization for the Research on Cancer (ARC); French
Ministry of work, solidarity, and public function (DGT); Organization
for the Research on Cancer; Federal Ministry of Education, Science,
Research, and Technology [01 HK 173/0]; Federal Ministry of Science [01
HK 546/8]; Ministry of Labour and Social Affairs [IIIb7-27/13]; European
Commission [IC15-CT96-0313]; Polish State Committee for Scientific
Research [SPUB-M-COPERNICUS/P-05/DZ-30/99/2000]; Roy Castle Foundation
as part of the Liverpool Lung Project; Intramural Research Program of
the National Institutes of Health, National Cancer Institute, Division
of Cancer Epidemiology and Genetics, Bethesda, Maryland; Environmental
Epidemiology Program of the Lombardy Region, Italy; Istituto Nazionale
per l'Assicurazione contro gli Infortuni sul Lavoro, Rome, Italy;
Italian Association for CancerResearch, Region Piedmont, Compagnia di
San Paolo; European Union Nuclear Fission Safety Program
[F14P-CT96-0055]; Lazio Region; Dutch Ministry of Health, Welfare and
Sports, National Institute of Public Health and the Environment; Europe
Against Cancer Program; Instituto Universitario de Oncologia,
Universidad de Oviedo, Asturias; Fondo de Investigacion Sanitaria (FIS);
Ciber de Epidemiologia y Salud Publica (CIBER-ESP), Spain;
SwedishCouncil for Work Life Research; Swedish Environmental Protection
Agency; Research Grants Council of the Hong Kong Special Administrative
Region, China [CUHK4460/03M]; Health Research Council of New Zealand;
New Zealand Department of Labour, Lottery Health Research; Cancer
Society of New Zealand
FX The SYNERGY project is funded by the German Social Accident Insurance
(DGUV). The Montreal case-control study of environmental causes of lung
cancer was supported by the Canadian Institutes for Health Research and
Guzzo-SRC Chair in Environment and Cancer. The Toronto lung cancer
case-control study was funded by the National Cancer Institute of Canada
with funds provided by the Canadian Cancer Society, and the occupational
analysis was conducted by the Occupational Cancer Research Centre, which
was supported by the Workplace Safety and Insurance Board, the Canadian
Cancer Society, and Cancer Care Ontario. The Investigations Cancers
Respiratoires et Environnement (ICARE) study was supported by the French
Agency of Health Security (ANSES), the Fondation de France, the French
National Research Agency (ANR), the National Institute of Cancer (INCA),
the Fondation for Medical Research (FRM), The French Institute for
Public Health Surveillance (InVS), The Health Ministry (DGS), the
Organization for the Research on Cancer (ARC), and the French Ministry
of work, solidarity, and public function (DGT). The lung cancer in
France study was supported by the Fondation de France. The lung cancer
study in Paris was funded by Organization for the Research on Cancer.
The Arbeit und Technik (AUT) study in Germany was funded by the Federal
Ministry of Education, Science, Research, and Technology (grant 01 HK
173/0). The Humanisierung des Arbeitslebens (HdA) study was funded by
the Federal Ministry of Science (grant 01 HK 546/8) and the Ministry of
Labour and Social Affairs (grant IIIb7-27/13). The International Agency
for Research on Cancer Multicenter Case-Control Study of Occupation,
Environment, and Lung Cancer in Central and Eastern Europe and the
United Kingdom (INCO) study was supported by a grant from the European
Commission's INCO-Copernicus program (contract IC15-CT96-0313). In
Warsaw, the study was supported by a grant from the Polish State
Committee for Scientific Research (grant
SPUB-M-COPERNICUS/P-05/DZ-30/99/2000). In Liverpool, the work was funded
by the Roy Castle Foundation as part of the Liverpool Lung Project. The
Environment and Genetics in Lung Cancer Etiology (EAGLE) study was
funded by the Intramural Research Program of the National Institutes of
Health, National Cancer Institute, Division of Cancer Epidemiology and
Genetics, Bethesda, Maryland; the Environmental Epidemiology Program of
the Lombardy Region, Italy; and the Istituto Nazionale per
l'Assicurazione contro gli Infortuni sul Lavoro, Rome, Italy.
TheTurin/Venetostudy(apopulation-basedcase-controlstudy of lung cancer
in the city of Turin and in the Eastern part of Veneto Region) was
supported by the Italian Association for CancerResearch, Region
Piedmont, Compagnia di San Paolo. The study in Rome was conducted with
partial support from the European Union Nuclear Fission Safety Program
(grant F14P-CT96-0055) and from the Lazio Region. The Monitoring van
Risicofactoren en Gezondheid in Nederland (MORGEN) study was supported
by the Dutch Ministry of Health, Welfare and Sports, National Institute
of Public Health and the Environment, and the Europe Against Cancer
Program. The Cancer de Pulmon en Asturias (CAPUA) study was supported by
the Instituto Universitario de Oncologia, Universidad de Oviedo,
Asturias, the Fondo de Investigacion Sanitaria (FIS) and the Ciber de
Epidemiologia y Salud Publica (CIBER-ESP), Spain. The Lungcancer i
Stockholm (LUCAS) study was supported by the SwedishCouncil for Work
Life Research and the Swedish Environmental Protection Agency.; The
study in Hong Kong was supported by a grant from the Research Grants
Council of the Hong Kong Special Administrative Region, China (project
CUHK4460/03M). The Occupational Cancer in New Zealand (OCANZ) study was
funded by the Health Research Council of New Zealand, the New Zealand
Department of Labour, Lottery Health Research, and by the Cancer Society
of New Zealand.
NR 37
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U1 2
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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 2013
VL 178
IS 9
BP 1355
EP 1365
DI 10.1093/aje/kwt119
PG 11
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 247SZ
UT WOS:000326642300002
PM 24068200
ER
PT J
AU Weinberger, DM
Bruden, DT
Grant, LR
Lipsitch, M
O'Brien, KL
Pelton, SI
Sanders, EAM
Feikin, DR
AF Weinberger, Daniel M.
Bruden, Dana T.
Grant, Lindsay R.
Lipsitch, Marc
O'Brien, Katherine L.
Pelton, Stephen I.
Sanders, Elisabeth A. M.
Feikin, Daniel R.
TI Using Pneumococcal Carriage Data to Monitor Postvaccination Changes in
Invasive Disease
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE carriage; conjugate vaccine; pneumococcal; pneumococcus; surveillance;
vaccine effectiveness; vaccines
ID CONJUGATE VACCINE USE; STREPTOCOCCUS-PNEUMONIAE; SEROTYPE REPLACEMENT;
ALASKAN CHILDREN; IMPACT; COLONIZATION; TRANSMISSION; DECADE
AB Pneumococcal conjugate vaccines (PCVs) have been introduced worldwide. However, few developing countries have high-quality surveillance systems available for monitoring vaccine impact. We evaluated whether data from nasopharyngeal carriage studies can be used to accurately monitor post-PCV changes in the incidence of invasive pneumococcal disease (IPD) among children under 5 years of age. For various dates during 19912010, data on nasopharyngeal pneumococcal carriage and on IPD before and after administration of 7-valent PCV (PCV7) were available from England and Wales, the Netherlands, the Navajo and White Mountain Apache American Indian populations, and the US states of Massachusetts and Alaska. We estimated the change in carriage prevalence for each serotype in each study and then either calculated the average change (inverse variance-weighted) among vaccine and nonvaccine serotypes (model 1) or used mixed-effects models to estimate the change for each serotype individually, pooling serotype data within or between studies (models 2 and 3). We then multiplied these values by the proportion of IPD caused by each serotype during the pre-PCV7 period to obtain an estimate of post-PCV7 disease incidence. Model 1 accurately captured overall changes in IPD incidence following PCV7 introduction for most studies, while the more detailed models, models 2 and 3, were less accurate. Carriage data can be used in this simple model to estimate post-PCV changes in IPD incidence.
C1 [Weinberger, Daniel M.] NIH, Div Int Epidemiol & Populat Studies, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Weinberger, Daniel M.] Yale Univ, Sch Publ Hlth, Dept Epidemiol Microbial Dis, New Haven, CT 06520 USA.
[Bruden, Dana T.] Ctr Dis Control & Prevent, Arctic Invest Program, Div Preparedness & Emerging Infect, Natl Ctr Emerging & Zoonot Infect Dis, Anchorage, AK USA.
[Grant, Lindsay R.; O'Brien, Katherine L.] Johns Hopkins Univ, Ctr Amer Indian Hlth, Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Lipsitch, Marc] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Lipsitch, Marc] Harvard Univ, Sch Publ Hlth, Dept Immunol & Infect Dis, Boston, MA 02115 USA.
[O'Brien, Katherine L.; Feikin, Daniel R.] Johns Hopkins Univ, Int Vaccine Access Ctr, Dept Int Hlth, Bloomberg Sch Publ Hlth, Baltimore, MD USA.
[Pelton, Stephen I.] Boston Univ, Sch Med, Dept Pediat, Boston Med Ctr, Boston, MA 02118 USA.
[Pelton, Stephen I.] Boston Univ, Sch Med, Sect Pediat Infect Dis, Boston Med Ctr, Boston, MA 02118 USA.
[Pelton, Stephen I.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA.
[Sanders, Elisabeth A. M.] Univ Med Ctr Utrecht, Wilhelmina Childrens Hosp, Dept Pediat Immunol & Infect Dis, Utrecht, Netherlands.
[Feikin, Daniel R.] Ctr Dis Control & Prevent, Div Preparedness & Emerging Infect, Natl Ctr Emerging & Zoonot Infect Dis, Atlanta, GA USA.
RP Weinberger, DM (reprint author), Yale Univ, Sch Publ Hlth, Dept Epidemiol Microbial Dis, POB 208034, New Haven, CT 06520 USA.
EM Daniel.weinberger@yale.edu
OI Pelton, Stephen/0000-0003-4862-5344; Lipsitch, Marc/0000-0003-1504-9213
FU Division of International Epidemiology and Population Studies, Fogarty
International Center, National Institutes of Health; National Institutes
of Health [2R01AI048935]; Bill and Melinda Gates Foundation [37875];
Native American Research Centers for Health [U26IHS300013/03,
U269400012-01]; Centers for Disease Control and Prevention National
Vaccine Program Office; Thrasher Research Fund [02820-9]; Wyeth Vaccines
(Pfizer Inc.); US Agency for International Development; World Health
Organization; Pfizer Inc. [WS950636]; Pfizer Inc. (New York, New York);
GlaxoSmithKline (GSK; London); GlaxoSmithKline (GSK; United Kingdom);
Pfizer; Wyeth (Overland Park, Kansas)/Pfizer; GSK; Novartis
FX D.M.W. was supported by the Division of International Epidemiology and
Population Studies, Fogarty International Center, National Institutes of
Health. M.L. was supported by National Institutes of Health grant
2R01AI048935. Support for the Navajo/WMA studies came from the Bill and
Melinda Gates Foundation (grant 37875), The Native American Research
Centers for Health (grants U26IHS300013/03 and U269400012-01), the
Centers for Disease Control and Prevention National Vaccine Program
Office, the Thrasher Research Fund (grant 02820-9), Wyeth Vaccines
(Pfizer Inc.), the US Agency for International Development, and the
World Health Organization. Support for the Alaskan postvaccine carriage
study was provided, in part, by a grant from Pfizer Inc. (grant
WS950636).; D.M.W. has received research funding from Pfizer Inc. (New
York, New York). K.O.B. and L.R.G. have received research grant support
related to pneumococcal vaccines from GlaxoSmithKline (GSK; London,
United Kingdom) and Pfizer. K.O.B. has received honoraria for
participation in external expert advisory committees on pneumococcal
vaccines convened by Merck & Company (Whitehouse Station, New Jersey),
Sanofi-Pasteur (Swiftwater, Pennsylvania), and GSK. E.A.M.S. has been
given research grant support related to pneumococcal vaccines from Wyeth
(Overland Park, Kansas)/Pfizer and GSK and has received honoraria for
participation in external expert advisory committees on pneumococcal
vaccines convened by Pfizer and GSK. S.I.P. has received honoraria for
participation in advisory board activities related to pneumococcal
vaccine or pneumococcal disease from Pfizer, Merck Vaccines, Novartis
(Basel, Switzerland), and GSKbio. M.L. has accepted honoraria or
consulting fees from Pfizer and Novartis.
NR 29
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U1 0
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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 2013
VL 178
IS 9
BP 1488
EP 1495
DI 10.1093/aje/kwt156
PG 8
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 247SZ
UT WOS:000326642300017
PM 24013204
ER
PT J
AU Pacchiarotti, I
Bond, DJ
Baldessarini, RJ
Nolen, WA
Grunze, H
Licht, RW
Post, RM
Berk, M
Goodwin, GM
Sachs, GS
Tondo, L
Findling, RL
Youngstrom, EA
Tohen, M
Undurraga, J
Gonzalez-Pinto, A
Goldberg, JF
Yildiz, A
Altshuler, LL
Calabrese, JR
Mitchell, PB
Thase, ME
Koukopoulos, A
Colom, F
Frye, MA
Malhi, GS
Fountoulakis, KN
Vazquez, G
Perlis, RH
Ketter, TA
Cassidy, F
Akiskal, H
Azorin, JM
Valenti, M
Mazzei, DH
Lafer, B
Kato, T
Mazzarini, L
Martinez-Aran, A
Parker, G
Souery, D
Ozerdem, A
McElroy, SL
Girardi, P
Bauer, M
Yatham, LN
Zarate, CA
Nierenberg, AA
Birmaher, B
Kanba, S
El-Mallakh, RS
Serretti, A
Rihmer, Z
Young, AH
Kotzalidis, GD
MacQueen, GM
Bowden, CL
Ghaemi, SN
Lopez-Jaramillo, C
Rybakowski, J
Ha, K
Perugi, G
Kasper, S
Amsterdam, JD
Hirschfeld, RM
Kapczinski, F
Vieta, E
AF Pacchiarotti, Isabella
Bond, David J.
Baldessarini, Ross J.
Nolen, Willem A.
Grunze, Heinz
Licht, Rasmus W.
Post, Robert M.
Berk, Michael
Goodwin, Guy M.
Sachs, Gary S.
Tondo, Leonardo
Findling, Robert L.
Youngstrom, Eric A.
Tohen, Mauricio
Undurraga, Juan
Gonzalez-Pinto, Ana
Goldberg, Joseph F.
Yildiz, Aysegul
Altshuler, Lori L.
Calabrese, Joseph R.
Mitchell, Philip B.
Thase, Michael E.
Koukopoulos, Athanasios
Colom, Francesc
Frye, Mark A.
Malhi, Gin S.
Fountoulakis, Konstantinos N.
Vazquez, Gustavo
Perlis, Roy H.
Ketter, Terence A.
Cassidy, Frederick
Akiskal, Hagop
Azorin, Jean-Michel
Valenti, Marc
Mazzei, Diego Hidalgo
Lafer, Beny
Kato, Tadafumi
Mazzarini, Lorenzo
Martinez-Aran, Anabel
Parker, Gordon
Souery, Daniel
Ozerdem, Aysegul
McElroy, Susan L.
Girardi, Paolo
Bauer, Michael
Yatham, Lakshmi N.
Zarate, Carlos A.
Nierenberg, Andrew A.
Birmaher, Boris
Kanba, Shigenobu
El-Mallakh, Rif S.
Serretti, Alessandro
Rihmer, Zoltan
Young, Allan H.
Kotzalidis, Georgios D.
MacQueen, Glenda M.
Bowden, Charles L.
Ghaemi, S. Nassir
Lopez-Jaramillo, Carlos
Rybakowski, Janusz
Ha, Kyooseob
Perugi, Giulio
Kasper, Siegfried
Amsterdam, Jay D.
Hirschfeld, Robert M.
Kapczinski, Flavio
Vieta, Eduard
TI The International Society for Bipolar Disorders (ISBD) Task Force Report
on Antidepressant Use in Bipolar Disorders
SO AMERICAN JOURNAL OF PSYCHIATRY
LA English
DT Review
ID TREATMENT ENHANCEMENT PROGRAM; MAJOR DEPRESSIVE EPISODE; LONG-TERM
FLUOXETINE; MOOD CONVERSION RATE; II DISORDER; STEP-BD; DOUBLE-BLIND;
LONGITUDINAL-EVALUATION; LITHIUM MONOTHERAPY; CONTROLLED-TRIALS
AB Objective: The risk-benefit profile of antidepressant medications in bipolar disorder is controversial. When conclusive evidence is lacking, expert consensus can guide treatment decisions. The International Society for Bipolar Disorders (ISBD) convened a task force to seek consensus recommendations on the use of antidepressants in bipolar disorders.
Method: An expert task force iteratively developed consensus through serial consensus-based revisions using the Delphi method. Initial survey items were based on systematic review of the literature. Subsequent surveys included new or reworded items and items that needed to be rerated. This process resulted in the final ISBD Task Force clinical recommendations on antidepressant use in bipolar disorder.
Results: There is striking incongruity between the wide use of and the weak evidence base for the efficacy and safety of antidepressant drugs in bipolar disorder. Few well-designed, long-term trials of prophylactic benefits have been conducted, and there is insufficient evidence for treatment benefits with antidepressants combined with mood stabilizers. A major concern is the risk for mood switch to hypomania, mania, and mixed states. Integrating the evidence and the experience of the task force members, a consensus was reached on 12 statements on the use of antidepressants in bipolar disorder.
Conclusions: Because of limited data, the task force could not make broad statements endorsing antidepressant use but acknowledged that individual bipolar patients may benefit from antidepressants. Regarding safety, serotonin reuptake inhibitors and bupropion may have lower rates of manic switch than tricyclic and tetracyclic antidepressants and norepinephrine-serotonin reuptake inhibitors. The frequency and severity of antidepressant-associated mood elevations appear to be greater in bipolar I than bipolar II disorder. Hence, in bipolar I patients antidepressants should be prescribed only as an adjunct to moodstabilizing medications.
C1 [Vieta, Eduard] Univ Barcelona, CIBERSAM Ctr Biomed Res Network Mental Hlth, IDIBAPS Inst Biomed Res August Pi & Sunyer, Bipolar Disorders Program,Clin Inst Neurosci,Hosp, Barcelona, Spain.
Univ British Columbia, Dept Psychiat, Mood Disorders Ctr, Vancouver, BC V5Z 1M9, Canada.
Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA.
Univ Groningen, Univ Med Ctr Groningen, Dept Psychiat, Groningen, Netherlands.
Newcastle Univ, Inst Neurosci, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England.
Aarhus Univ Hosp, Mood Disorders Res Unit, Risskov, Denmark.
Bipolar Collaborat Network, Bethesda, MD USA.
Deakin Univ, Sch Med, Geelong, Vic 3217, Australia.
Warneford Hosp, Univ Dept Psychiat, Oxford OX3 7JX, England.
Massachusetts Gen Hosp, Bipolar Clin, Boston, MA 02114 USA.
Massachusetts Gen Hosp, Res Program, Boston, MA 02114 USA.
Lucio Bini Mood Disorder Ctr, Cagliari, Italy.
Case Western Reserve Univ, Sch Med, Div Child & Adolescent Psychiat, Cleveland, OH 44106 USA.
Johns Hopkins Childrens Ctr, Baltimore, MD USA.
Univ N Carolina, Dept Psychol, Chapel Hill, NC USA.
Univ New Mexico, Sch Med, Dept Psychiat, Albuquerque, NM 87131 USA.
Univ Basque Country, Santiago Apostol Hosp, Dept Psychiat, CIBERSAM, Vitoria, Spain.
Mt Sinai Sch Med, Dept Psychiat, New York, NY USA.
Dokuz Eylul Univ, Dept Psychiat, Izmir, Turkey.
Dokuz Eylul Univ, Dept Neurosci, Izmir, Turkey.
Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Behav Sci, Los Angeles, CA 90095 USA.
Univ New S Wales, Sch Psychiat, Randwick, NSW, Australia.
Prince Wales Hosp, Black Dog Inst, Randwick, NSW 2031, Australia.
Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA.
Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA.
Ctr Lucio Bini, Rome, Italy.
Mayo Clin, Integrated Mood Grp, Dept Psychiat, Rochester, MN USA.
Mayo Clin, Integrated Mood Grp, Dept Psychol, Rochester, MN USA.
Univ Sydney, Discipline Psychiat, CADE Clin, Sydney, NSW 2006, Australia.
Aristotle Univ Thessaloniki, Sch Med, Dept Psychiat 3, GR-54006 Thessaloniki, Greece.
Univ Palermo, Dept Neurosci, Buenos Aires, DF, Argentina.
Stanford Univ, Sch Med, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA.
Duke Univ, Med Ctr, Durham, NC USA.
Univ Calif San Diego, Int Mood Ctr, La Jolla, CA 92093 USA.
Hop St Marguerite, Marseille, France.
Univ Sao Paulo, Sch Med, Bipolar Res Program, Dept & Inst Psychiat, Sao Paulo, Brazil.
RIKEN Brain Sci Inst, Lab Mol Dynam Mental Disorders, Saitama, Japan.
Univ Roma La Sapienza, Sch Med & Psychol, NESMOS Dept, St Andrea Hosp, I-00185 Rome, Italy.
Univ Libre Brussels, Lab Med Psychol, Brussels, Belgium.
European Ctr Med Psychol, Brussels, Belgium.
Univ Cincinnati, Coll Med, Cincinnati, OH USA.
Tech Univ Dresden, Univ Hosp Carl Gustav Carus, Dept Psychiat & Psychotherapy, Dresden, Germany.
NIMH, Bethesda, MD 20892 USA.
Western Psychiat Inst & Clin, Dept Psychiat, Pittsburgh, PA USA.
Kyushu Univ, Grad Sch Med Sci, Dept Neuropsychiat, Fukuoka 812, Japan.
Univ Louisville, Louisville, KY 40292 USA.
Univ Bologna, Dept Biomed & Neuromotor Sci, Bologna, Italy.
Semmelweis Univ, Dept Clin & Theoret Mental Hlth, H-1085 Budapest, Hungary.
Univ London Imperial Coll Sci Technol & Med, London SW7 2AZ, England.
Univ Calgary, Dept Psychiat, Calgary, AB, Canada.
Univ Texas Hlth Sci Ctr San Antonio, Dept Psychiat, San Antonio, TX USA.
Tufts Univ, Sch Med, Dept Psychiat, Mood Disorders Program,Tufts Med Ctr, Boston, MA 02111 USA.
Univ Antioquia, Dept Psychiat, Fdn San Vicente de Paul, Mood Disorders Program, Medellin, Colombia.
Poznan Univ Med Sci, Dept Adult Psychiat, Poznan, Poland.
Seoul Natl Univ, Bundang Hosp, Dept Psychiat, Mood Disorders Clin, Bundang, South Korea.
Seoul Natl Univ, Bundang Hosp, Dept Psychiat, Clin Affect Neurosci Lab, Bundang, South Korea.
Univ Pisa, Dept Psychiat, Pisa, Italy.
Med Univ Vienna, Dept Psychiat & Psychotherapy, Vienna, Austria.
Univ Penn, Sch Med, Dept Psychiat, Depress Res Unit, Philadelphia, PA 19104 USA.
Univ Texas Med Branch, Dept Psychiat & Behav Sci, Galveston, TX 77555 USA.
Univ Fed Rio Grande do Sul, Hosp Clin Porto Alegre, Lab Mol Psychiat, Porto Alegre, RS, Brazil.
RP Vieta, E (reprint author), Univ Barcelona, CIBERSAM Ctr Biomed Res Network Mental Hlth, IDIBAPS Inst Biomed Res August Pi & Sunyer, Bipolar Disorders Program,Clin Inst Neurosci,Hosp, Barcelona, Spain.
EM evieta@clinic.ub.es
RI Nolen, Willem/E-9006-2014; Kato, Tadafumi/J-3583-2014; Kapczinski,
Flavio/J-5803-2014; Lafer, Beny/F-9390-2015; Undurraga,
Juan/F-3438-2012; Lafer, Beny/C-1055-2012;
OI Colom, Francesc/0000-0002-9516-9030; Vieta, Eduard/0000-0002-0548-0053;
Parker, Gordon/0000-0003-3424-5519; Grunze, Heinz/0000-0003-4712-8979;
Kato, Tadafumi/0000-0001-7856-3952; Lafer, Beny/0000-0002-6132-9999;
Undurraga, Juan/0000-0001-6958-2369; Lafer, Beny/0000-0002-6132-9999;
Martinez-Aran, Anabel/0000-0002-0623-6263; VALENTI,
MARC/0000-0002-9783-6220; Mitchell, Philip/0000-0002-7954-5235; Lopez,
Carlos/0000-0002-1875-1369; Berk, Michael/0000-0002-5554-6946
FU Canadian Institutes of Health Research; UBC Institute of Mental
Health/Coast Capital Depression Research Fund; Pfizer; Netherlands
Organization for Health Research and Development; European Union;
Stanley Medical Research Institute; AstraZeneca; GlaxoSmithKline; Wyeth;
Lundbeck; Bristol-Myers Squibb; Desitin; Eli Lilly; Gedeon-Richter;
Hoffmann-La Roche; Janssen-Cilag; Merck; Otsuka; Sanofi-Aventis;
Servier; Sepracor; UBC; Medical Research Council; National Institute for
Health Research (U.K.); Cambridge University Press; Igaku-Shoin; Solal
Ed.; Ars Medica; Giovani Fioriti Ed.; Medipage; La Esfera de Los Libros;
Morales i Torres Ed; Panamericana; Mayo Ed. Columna; Mayo Foundation;
Myriad; NARSAD; National Institute of Alcohol Abuse and Alcoholism; H;
Journal of Affective Disorders; University of Lisbon; Aristotle
University of Thesaloniki; Sanofi, Nevada Psychiatric Association;
Medical Education Speakers Network; Sanofi; CAPES (Coordination for the
Improvement of Higher Education Personnel); FAPESP (Sao Paulo Research
Foundation); CNPq (National Council for Scientific and Technological
Development); Janssen; Schering; Springer Healthcare; Abbott
Laboratories; Agency for Healthcare Research and Quality; American Drug
Utilization Review Society; American Society for Clinical
Psychopharmacology; Basilea; Biomedical Development, Boston Center for
the Arts; BrainCells; Brandeis University; Cederroth; Cephalon; Corcept;
Cyberonics; East Asian Bipolar Forum; Elan; Forest; Genaissance; Harold
Grinspoon Charitable Foundation; Health New England; Innapharma;
International Society for Bipolar Disorder; Jazz Pharmaceuticals;
Lichtwer Pharma; MGH Psychiatry Academy; Mid-Atlantic Permanente
Research Institute; Mylan; NIMH; Novartis; PamLab; PGx Health; Ridge
Diagnostics; Roche; Schering-Plough; Shire, Somerset; Stanley
Foundation; Sunovion, Takeda; Targacept; Teva, University of Pisa;
University of Wisconsin at Madison; University of Texas Southwestern
Medical Center at Dallas; Wyeth-Ayerst; Zucker Hillside Hospital;
Astellas; Dainippon Sumitomo; Eisai; Eli Lilly Japan; Kyowa Hakko Kirin;
Meiji Seika Pharma; MSD; Ono; Shionogi; Taisho Toyama; Yoshitomiyakuhin;
Janssen Cilag; NIH; University of Antioquia
FX Dr. Bond has received honoraria from the Canadian Network for Mood and
Anxiety Treatments, the Canadian Psychiatric Association, Pfizer,
Sunovion, Bristol-Myers Squibb, Otsuka, AstraZeneca, and Janssen-Ortho;
and has received research grants from the Canadian Institutes of Health
Research, the UBC Institute of Mental Health/Coast Capital Depression
Research Fund, and Pfizer. Dr. Nolen has received grants from the
Netherlands Organization for Health Research and Development, the
European Union, the Stanley Medical Research Institute, AstraZeneca,
GlaxoSmithKline, and Wyeth and honoraria or speaking fees from
AstraZeneca and Lundbeck. Dr. Grunze has received research support,
consulting fees, or honoraria from AstraZeneca, Bristol-Myers Squibb,
Desitin, Eli Lilly, Gedeon-Richter, Hoffmann-La Roche, Janssen-Cilag,
Lundbeck, Merck, Otsuka, Sanofi-Aventis, Servier, Sepracor, and UBC. Dr.
Licht has served on advisory boards for Bristol-Myers Squibb,
AstraZeneca, and MSD and has received honoraria from AstraZeneca,
Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Janssen-Cilag,
Lundbeck, and Pfizer. Dr. Post has served as a consultant or speaker for
AstraZeneca, Sunovion, Teva, and Validas. Dr. Berk has received research
support from or served as a consultant or speaker for AstraZeneca,
Beyond Blue, Bristol-Myers Squibb, Cancer Council of Victoria,
Cooperative Research Centre, Eli Lilly, Geelong Medical Research
Foundation, GlaxoSmithKline, Janssen Cilag, Lundbeck, Mayne Pharma, MBF,
Meat and Livestock Board, Merck, National Health and Medical Research
Council (Australia), NIH, Novartis, Organon, Pfizer, Rotary Health,
Sanofi Synthelabo, Servier, Simons Autism Foundation, Stanley Medical
Research Foundation, Solvay, Woolworths, and Wyeth and is a co-inventor
on two provisional patents regarding the use of N-acetylcysteine and
related compounds for psychiatric indications. Dr. Goodwin has received
grants from Bailly Thomas, Medical Research Council, National Institute
for Health Research (U.K.), and Servier, has served as consultant,
adviser, or CME speaker for AstraZeneca, Bristol-Myers Squibb,
Boehringer Ingelheim, Cephalon/Teva Janssen-Cilag, Eli Lilly, Lundbeck,
Otsuka, P1Vital, Roche, Servier, Schering-Plough, Shire, Sunovion, and
Takeda, and holds shares in P1Vital. Dr. Sachs has served on advisory
boards for Elan, Janssen, Merck, Otsuka, Roche, Sunovion, and Takeda.
Dr. Findling has received research support or served as a consultant or
speaker for Alexza Pharmaceuticals, American Psychiatric Publishing,
AstraZeneca, Bracket, Bristol-Myers Squibb, Clinsys, Cognition Group,
Forest, GlaxoSmithKline, Guilford Press, Johns Hopkins University Press,
Johnson & Johnson, KemPharm, Lilly, Lundbeck, Merck, NIH, Novartis,
Noven, Otsuka, Oxford University Press, Pfizer, Physicians Postgraduate
Press, Rhodes Pharmaceuticals, Roche, Sage, Seaside Pharmaceuticals,
Shire, Stanley Medical Research Institute, Sunovion, Supernus
Pharmaceuticals, Transcept Pharmaceuticals, Validus, and WebMD. Dr.
Youngstrom has served as a consultant for Lundbeck. Dr. Tohen has
received honoraria from or served as a consultant for AstraZeneca,
Bristol-Myers Squibb, Elan, Eli Lilly, Forest, GlaxoSmithKline, Johnson
& Johnson, Lundbeck, Merck, Otsuka, PamLab, Roche, Sunovion, Teva,
Wyeth, and Wiley Publishing; his spouse is an employee and stockholder
at Eli Lilly. Dr.; Gonzalez-Pinto has received grants from or served as
consultant, adviser, or CME speaker for Almirall, AstraZeneca,
Bristol-Myers Squibb, Cephalon, Eli Lilly, GlaxoSmithKline,
Janssen-Cilag, Jazz, Johnson & Johnson, Lundbeck, Merck, Otsuka, Pfizer,
Sanofi-Aventis, Servier, Schering-Plough, Solvay, the Spanish Ministry
of Science and Innovation (CIBERSAM), the Ministry of Science (Carlos
III Institute), the Basque Government, Stanley Medical Research
Institute, and Wyeth. Dr. Goldberg has served as consultant or speaker
for AstraZeneca, Grunenthal Group, Medscape, Merck, Mylan
Pharmaceuticals, Novartis, Sunovion, and WebMD and receives royalties
from American Psychiatric Publishing. Dr. Yildiz has received research
grants from or served as a consultant or speaker for Abdi Ibrahim,
Actavis, Ali Raif, AstraZeneca, Bristol-Myers Squibb, Janssen-Cilag,
Lundbeck, Pfizer, Sanofi-Aventis, and Servier. Dr. Altshuler has served
on advisory boards or as a consultant for Eli Lilly, Takeda
Pharmaceuticals North America, Lundbeck, Sepracor, and Sunovion. Dr.
Calabrese has received funding or research support from or served as a
consultant or CME speaker or on advisory boards for Abbott, AstraZeneca,
Bristol-Myers Squibb, Cephalon, Cleveland Foundation, Dainippon
Sumitomo, Department of Defense, Eli Lilly, EPI-Q, Forest, France
Foundation, GlaxoSmithKline, Health Resources Services Administration,
Janssen, Johnson & Johnson, Lundbeck, Merck, NARSAD, Neurosearch, NIMH,
Ortho-McNeil, Otsuka, Pfizer, Repligen, Sanofi-Aventis, Schering-Plough,
Servier, Solvay, Stanley Medical Research Institute, Supernus, Synosia,
Takeda, and Wyeth. Dr. Thase has received grant funding from or served
as a consultant for Agency for Healthcare Research and Quality,
Alkermes, Allergan, AstraZeneca, Bristol-Myers Squibb, Dey Pharma, Eli
Lilly, Forest Laboratories, Forest Pharmaceuticals, Gerson Lehman Group,
GlaxoSmithKline, Guidepoint Global, Lundbeck, MedAvante, Merck, NeoSync,
Neuronetics, NIMH, Novartis, Otsuka, Ortho-McNeil Pharmaceuticals,
PamLab, Pfizer (formerly Wyeth-Ayerst Laboratories), PharmaNeuroboost,
Roche Laboratories, Shire US, Sunovion, Takeda, Teva, and Transcept; he
receives royalties from American Psychiatric Foundation, Guilford
Publications, Herald House, Oxford University Press, and W. W. Norton
and has equity holdings in MedAvante; his wife is employed by Peloton
Advantage, which does business with Pfizer. Dr. Colom has served as
adviser or speaker for Adamed, AstraZeneca, Bristol-Myers Squibb, Eli
Lilly, GlaxoSmithKline, Lundbeck, MSD-Merck, Otsuka, Pfizer,
Sanofi-Aventis, Shire, and Tecnifar and has received copyright fees from
Cambridge University Press, Igaku-Shoin, Solal Ed., Ars Medica, Giovani
Fioriti Ed., Medipage, La Esfera de Los Libros, Morales i Torres Ed,
Panamericana, and Mayo Ed. & Columna. Dr. Frye has received grant
support from the Mayo Foundation, Myriad, NARSAD, the National Institute
of Alcohol Abuse and Alcoholism, NIMH, and Pfizer and travel support
from Advanced Health Media, AstraZeneca, Bristol-Myers Squibb, Chilean
Society of Neurology, Psychiatry, and Neurosurgery, Colombian Society of
Neuropsychopharmacology, GlaxoSmithKline, Otsuka, and Sanofi-Aventis; he
has served as an unpaid consultant for Allergan, Merck, Myriad,
Sanofi-Aventis, Sunovion, Takeda Global Research, Teva Pharmaceuticals,
and United Biosource Corporation. Dr. Malhi has received research
support from or served as a speaker or consultant for AstraZeneca, Eli
Lilly, Janssen-Cilag, Lundbeck, Organon, Pfizer, Ranbaxy, Servier, and
Wyeth. Dr.; Fountoulakis has received research support or travel support
from or served as a speaker or consultant for AstraZeneca, Bristol-Myers
Squibb, Janssen-Cilag, Eli Lilly, Pfizer Foundation, and Wyeth. Dr.
Vazquez has served as consultant or speaker for AstraZeneca, Gador,
GlaxoSmithKline, Ivax, Eli Lilly, Lundbeck, Pfizer, Raffo, Servier, and
Novartis. Dr. Perlis has served on advisory boards or as a consultant
for Genomind, Healthrageous, PamLab, Pfizer, Proteus Biomedical, and
RIDVentures. Dr. Ketter has received research support from or served as
a consultant or speaker for Abbott, Allergan, AstraZeneca, Avanir,
Bristol-Myers Squibb, Cephalon, Eli Lilly, Forest Pharmaceuticals,
GlaxoSmithKline, Janssen, Merck, Otsuka, Pfizer, Sunovion, and Teva; he
receives royalties from American Psychiatric Publishing, and his spouse
is an employee of and holds stock in Janssen Pharmaceuticals. Dr.
Akiskal receives honoraria or fees from Journal of Affective Disorders,
AstraZeneca, University of Lisbon, Aristotle University of Thesaloniki,
Sanofi, Nevada Psychiatric Association, and Medical Education Speakers
Network. Dr. Azorin has received grants from Eli Lilly and Sanofi and
honoraria from AstraZeneca, Bristol-Myers Squibb, Lundbeck Servier, and
Eli Lilly; he has served on advisory boards for Eli Lilly, Lundbeck,
Bristol-Myers Squibb, and Roche and as an expert witness for Eli Lilly.
Dr. Lafer has received grant or research support from Brazilian research
agencies CAPES (Coordination for the Improvement of Higher Education
Personnel), FAPESP (Sao Paulo Research Foundation), and CNPq (National
Council for Scientific and Technological Development). Dr. Kato has
received research support from Takeda and honoraria for lectures,
manuscripts, or consultancy from Kyowa Hakko Kirin, Eli Lilly Japan,
Otsuka, GlaxoSmithKline, Taisho Toyama Pharmaceutical, Dainippon
Sumitomo, Meiji Seika Pharma, Pfizer Japan, Mochida Pharmaceutical,
Shionogi, Janssen, and Astellas. Dr. Martinez-Aran has served as speaker
or adviser for Bristol-Myers Squibb, Lundbeck, Otsuka, and Pfizer. Dr.
Parker has served as a speaker or on advisory boards for or received
travel or speaking fees from AstraZeneca, Eli Lilly, Lundbeck, Pfizer,
and Servier. Dr. Souery has served on advisory boards for AstraZeneca
and Lundbeck and has received unrestricted grants for clinical research
and educational activities from AstraZeneca, GlaxoSmithKline, and
Lundbeck. Dr. Ozerdem has received honoraria or travel support from Abdi
Ibrahim, Adeka, AstraZeneca, Bristol-Myers Squibb, EGIS,
GlaxoSmithKline, Lundbeck, Nobel, Pfizer, Schering-Plough, and Servier.
Dr. McElroy has served as a consultant for or on scientific advisory
boards for Alkermes, Bracket, Corcept, MedAvante, Shire, Sunovion, and
Teva; she is a principal or co-investigator on studies sponsored by the
Agency for Healthcare Research and Quality, Alkermes, AstraZeneca,
Cephalon, Eli Lilly, Forest, Marriott Foundation, NIMH, Orexigen
Therapeutics, Pfizer, Shire, Takeda, and Transcept; she is also an
inventor on a patent for use of sulfamate derivatives for treating
impulse control disorders. Dr. Girardi has received research support
from, served on advisory boards for, and received honoraria from Eli
Lilly, Janssen, Otsuka, Pfizer, Schering, and Springer Healthcare. Dr.;
Bauer has received research support from or served as a consultant or
speaker for Alkermes, American Foundation for Suicide Prevention,
AstraZeneca, Bristol-Myers Squibb, Bundesministerium fur Bildung und
Forschung, Deutsche Forschungsgemeinschaft, European Commission (FP7),
Ferrer Internacional, GlaxoSmithKline, Janssen, Eli Lilly, Lundbeck,
NARSAD, Otsuka, Pfizer, Servier, Stanley Medical Research Institute, and
Takeda. Dr. Yatham has received research support from or served as a
speaker or advisory board member for AstraZeneca, Bristol-Myers Squibb,
Eli Lilly, Janssen, GlaxoSmithKline, Lundbeck, Novartis, Pfizer,
Servier, and Sunovion. Dr. Zarate is listed as a co-inventor on a patent
application for the use of ketamine and its metabolites in major
depression. Dr. Nierenberg has received research support from, served as
a consultant for, or received honoraria from Abbott Laboratories, Agency
for Healthcare Research and Quality, American Drug Utilization Review
Society, American Society for Clinical Psychopharmacology, AstraZeneca,
Basilea, Biomedical Development, Boston Center for the Arts, BrainCells,
Brandeis University, Bristol-Myers Squibb, Cederroth, Cephalon, Corcept,
Cyberonics, East Asian Bipolar Forum, Elan, Eli Lilly, Forest,
Genaissance, GlaxoSmithKline, Harold Grinspoon Charitable Foundation,
Health New England, Innapharma, International Society for Bipolar
Disorder, Janssen, Jazz Pharmaceuticals, Lichtwer Pharma, Lundbeck,
Merck, MGH Psychiatry Academy, Mid-Atlantic Permanente Research
Institute, Mylan (formerly Dey Pharmaceuticals), NARSAD, NIMH, Novartis,
PamLab, Pfizer, PGx Health, Ridge Diagnostics, Roche, Sepracor,
Schering-Plough, Shire, Somerset, Stanley Foundation, Sunovion, Takeda,
Targacept, Teva, University of Pisa, University of Wisconsin at Madison,
University of Texas Southwestern Medical Center at Dallas, Wyeth-Ayerst,
and Zucker Hillside Hospital; he receives other income from legal case
reviews for CRICO, MBL Publishing for past services as editor-in-chief
of CNS Spectrums, Slack Inc. for services as associate editor of
Psychiatric Annals, and from Belvoir Publications for serving on the
editorial board of Mind, Mood, and Memory; he has copyright joint
ownership with MGH for the Structured Clinical Interview for MADRS and
Clinical Positive Affect Scale and is a stakeholder in Appliance
Computing (MindSite), Brain Cells, and InfoMed. Dr. Birmaher has
received research support from NIMH and royalties from Random House,
Lippincott Williams & Wilkins, and UpToDate. Dr. Kanba has received
research support or honoraria from Astellas, Dainippon Sumitomo, Eisai,
Eli Lilly Japan, GlaxoSmithKline, Janssen, Kyowa Hakko Kirin, Meiji
Seika Pharma, MSD, Ono, Otsuka, Pfizer, Shionogi, Taisho Toyama, Wyeth,
and Yoshitomiyakuhin. Dr. El-Mallakh has received research support from
Merck and has served as a speaker for AstraZeneca and Otsuka. Dr.
Serretti has served as a consultant or speaker for Abbott, Angelini,
AstraZeneca, Bristol-Myers Squibb, Boehringer, Clinical Data, Eli Lilly,
GlaxoSmithKline, Italfarmaco, Janssen, Lundbeck, Pfizer, Sanofi, and
Servier. Dr. MacQueen has received research support from AstraZeneca and
served as a consultant or speaker for Bristol-Myers Squibb, Canadian
Psychiatric Association, Eli Lilly, Lundbeck, Norlien Foundation,
Pfizer, Sanofi, and Servier. Dr. Bowden has received grant support from
Novartis. Dr. Ghaemi has received research support from Takeda and has
served as a consultant for Sunovion. Dr.; Lopez-Jaramillo has received
research support from Janssen Cilag, Lundbeck, NIH, Novartis, Pfizer,
and University of Antioquia and honoraria from Abbott, GlaxoSmithKline,
Eli Lilly, Lundbeck, Pfizer, Sanofi, and Servier. Dr. Ha has received
research support or honoraria from AstraZeneca, Eli Lilly, Pfizer, and
Otsuka. Dr. Perugi has received research support from or served as a
consultant, speaker, or advisory board member for AstraZeneca,
Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Janssen-Cilag,
Lundbeck, and Sanofi-Aventis. Dr. Kasper has received research support
from or served as a consultant, speaker, or advisory board member for
Angelini, AstraZeneca, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline,
Janssen, Lundbeck, MSD, Neuraxpharm, Novartis, Organon, Pfizer, Pierre
Fabre, Schwabe, Sepracor, and Servier. Dr. Hirschfeld has served as a
consultant for or received honoraria from American College of
Psychiatrists, Biostrategies, Brown University, CME Alliance, CME
Outfitters, Equinox Group, Grey Healthcare, Letters & Sciences, Merck
Manual Editorial Board, Nevada Psychiatric Association, and Physicians
Post Graduate Press Health and Wellness Partners and receives royalties
from Jones & Bartlett and Taylor & Francis. Dr. Kapczinski has received
research support from or served as a consultant or speaker for
AstraZeneca, CNPq, CAPES, Eli Lilly, Janssen, Janssen-Cilag, NARSAD,
Stanley Medical Research Institute, and Servier. Dr. Vieta has received
research support from or served as consultant, adviser, or speaker for
Alexza, Almirall, AstraZeneca, Bristol-Myers Squibb, Elan, Eli Lilly,
Ferrer, Forest Research Institute, 7th Framework Program of the European
Union, Geodon Richter, GlaxoSmithKline, Janssen-Cilag, Jazz, Lundbeck,
Merck, Novartis, Organon, Otsuka, Pfizer, Roche, Sanofi-Aventis,
Servier, Solvay, Schering-Plough, Shire, Spanish Ministry of Science and
Innovation, Stanley Medical Research Institute, Takeda, Teva, United
Biosource Corporation, and Wyeth. The remaining authors report no
competing interests.
NR 102
TC 172
Z9 174
U1 4
U2 30
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 2013
VL 170
IS 11
BP 1249
EP 1262
DI 10.1176/appi.ajp.2013.13020185
PG 14
WC Psychiatry
SC Psychiatry
GA 248SZ
UT WOS:000326724300008
PM 24030475
ER
PT J
AU Wang, F
Yeung, KL
Chan, WC
Kwok, CCH
Leung, SL
Wu, C
Chan, EYY
Yu, ITS
Yang, XR
Tse, LA
AF Wang, F.
Yeung, K. L.
Chan, W. C.
Kwok, C. C. H.
Leung, S. L.
Wu, C.
Chan, E. Y. Y.
Yu, I. T. S.
Yang, X. R.
Tse, L. A.
TI A meta-analysis on dose-response relationship between night shift work
and the risk of breast cancer
SO ANNALS OF ONCOLOGY
LA English
DT Review
DE breast cancer; case-control studies; cohort studies; dose-response
relationship; meta-analysis; shift work
ID VITAMIN-D; NORWEGIAN NURSES; COHORT; WOMEN; HEALTH; LIGHT
AB This study aimed to conduct a systematic review to sum up evidence of the associations between different aspects of night shift work and female breast cancer using a dose-response meta-analysis approach.
We systematicly searched all cohort and case-control studies published in English on MEDLINE, Embase, PSYCInfo, APC Journal Club and Global Health, from January 1971 to May 2013. We extracted effect measures (relative risk, RR; odd ratio, OR; or hazard ratio, HR) from individual studies to generate pooled results using meta-analysis approaches. A log-linear dose-response regression model was used to evaluate the relationship between various indicators of exposure to night shift work and breast cancer risk. Downs and Black scale was applied to assess the methodological quality of included studies.
Ten studies were included in the meta-analysis. A pooled adjusted relative risk for the association between 'ever exposed to night shift work' and breast cancer was 1.19 [95% confidence interval (CI) 1.05-1.35]. Further meta-analyses on dose-response relationship showed that every 5-year increase of exposure to night shift work would correspondingly enhance the risk of breast cancer of the female by 3% (pooled RR = 1.03, 95% CI 1.01-1.05; P-heterogeneity < 0.001). Our meta-analysis also suggested that an increase in 500-night shifts would result in a 13% (RR = 1.13, 95% CI 1.07-1.21; P-heterogeneity = 0.06) increase in breast cancer risk.
This systematic review updated the evidence that a positive dose-response relationship is likely to present for breast cancer with increasing years of employment and cumulative shifts involved in the work.
C1 [Wang, F.; Yeung, K. L.; Chan, E. Y. Y.; Yu, I. T. S.; Tse, L. A.] Chinese Univ Hong Kong, JC Sch Publ Hlth & Primary Care, Sha Tin, Hong Kong, Peoples R China.
[Chan, W. C.] North Dist Hosp, Dept Surg, Hong Kong, Hong Kong, Peoples R China.
[Kwok, C. C. H.] Princess Margaret Hosp, Dept Oncol, Hong Kong, Hong Kong, Peoples R China.
[Leung, S. L.] Yan Chai Hosp, Dept Surg, Hong Kong, Hong Kong, Peoples R China.
[Wu, C.] North Dist Hosp, Dept Pathol, Hong Kong, Hong Kong, Peoples R China.
[Yang, X. R.] Natl Canc Inst, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD USA.
RP Tse, LA (reprint author), Chinese Univ Hong Kong, JC Sch Publ Hlth & Primary Care, Prince Wales Hosp, Sch Public Hlth & Primary Care 4 F, Sha Tin, Hong Kong, Peoples R China.
EM shelly@cuhk.edu.hk
RI Yu, Ignatius Tak Sun/A-9936-2008
FU Research Grants Council of Hong Kong [474811]
FX This work was supported by Research Grants Council of Hong Kong [Grant
number 474811].
NR 32
TC 53
Z9 54
U1 5
U2 32
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 2013
VL 24
IS 11
BP 2724
EP 2732
DI 10.1093/annonc/mdt283
PG 9
WC Oncology
SC Oncology
GA 247TF
UT WOS:000326643200004
PM 23975662
ER
PT J
AU Ramalingam, S
Crawford, J
Chang, A
Manegold, C
Perez-Soler, R
Douillard, JY
Thatcher, N
Barlesi, F
Owonikoko, T
Wang, Y
Pultar, P
Zhu, J
Malik, R
Giaccone, G
AF Ramalingam, S.
Crawford, J.
Chang, A.
Manegold, C.
Perez-Soler, R.
Douillard, J. -Y.
Thatcher, N.
Barlesi, F.
Owonikoko, T.
Wang, Y.
Pultar, P.
Zhu, J.
Malik, R.
Giaccone, G.
CA FORTIS-M Study Investigators
TI Talactoferrin alfa versus placebo in patients with refractory advanced
non-small-cell lung cancer (FORTIS-M trial)
SO ANNALS OF ONCOLOGY
LA English
DT Article
DE non-small-cell lung cancer; immunotherapy; phase III study;
talactoferrin
ID LACTOFERRIN INHIBITS GROWTH; ORAL TALACTOFERRIN; SUPPORTIVE CARE;
DOUBLE-BLIND; CHEMOTHERAPY; GEFITINIB; TUMORS; THERAPY; IMMUNOTHERAPY;
ERLOTINIB
AB Talactoferrin alfa is an oral dendritic cell (DC)-mediated immunotherapy (DCMI). We tested whether talactoferrin was superior to placebo in advanced non-small-cell lung cancer (NSCLC).
An FORTIS-M trial was an international, multicenter, randomized, double-blind comparison of talactoferrin (1.5 g p.o. BID) versus placebo BID, in patients with stage IIIB/IV NSCLC whose disease had failed two or more prior regimens. Treatment was administered for a maximum of five 14-week cycles. The primary efficacy end point was overall survival (OS); secondary end points included 6- and 12-month survival, progression-free survival (PFS), and disease control rate (DCR).
Seven hundred and forty-two patients were randomly assigned (2:1) to talactoferrin (497) or placebo (245). The median OS in the intent-to-treat (ITT) population was 7.66 months in the placebo arm and 7.49 months in the talactoferrin arm [hazard ratio (HR), 1.04; 95% CI, 0.873-1.24; P = 0.6602]. The 6-month survival rates were 59.9% (95% CI, 53.4% to 65.8%) and 55.7% (95% CI, 51.1% to 59.9%), respectively. The 12-month survival rates were 32.2% (95% CI, 26.3% to 38.2%) and 30.9% (95% CI, 26.8% to 35%), respectively. The median PFS rates were 1.64 months and 1.68 months, respectively (HR, 0.99; 95% CI, 0.835-1.16; P = 0.8073). The DCRs were 38.4 and 37.6%, respectively [stratified odds ratio (OR), 0.96; 95% CI, 0.698-1.33; P = 0.8336]. The safety profiles were comparable between arms.
There was no improvement in efficacy with talactoferrin alfa in patients with advanced NSCLC whose disease had failed two or more previous regimens.
C1 [Ramalingam, S.; Owonikoko, T.] Emory Univ, Robert W Woodruff Hlth Sci Ctr, Dept Oncol, Atlanta, GA 30322 USA.
[Crawford, J.] Duke Univ, Med Ctr, Dept Oncol, Durham, NC 27706 USA.
[Chang, A.] Johns Hopkins Singapore Int Med Ctr, Singapore, Singapore.
[Manegold, C.] Univ Med Ctr, Mannheim, Germany.
[Perez-Soler, R.] Albert Einstein Coll Med, Montefiore Med Ctr, Dept Oncol, New York, NY USA.
[Douillard, J. -Y.] Univ Nantes, Rene Gauducheau Canc Ctr, Dept Med Oncol, Nantes, France.
[Thatcher, N.] Christie NHS Fdn Trust, Dept Oncol, Manchester, Lancs, England.
[Barlesi, F.] Univ Aix Marseille 2, Marseille, France.
[Wang, Y.; Pultar, P.; Zhu, J.; Malik, R.] Agennix Inc, Dept Oncol, Princeton, NJ USA.
[Giaccone, G.] NCI, Dept Oncol, NIH, Bethesda, MD 20892 USA.
RP Giaccone, G (reprint author), Georgetown Univ, Lombardi Comprehens Canc Ctr, Dept Oncol, 3970 Reservoir Rd, Washington, DC 20007 USA.
EM gg496@geogetown.edu
RI Ottensmeier, Christian/E-8131-2012; Giaccone, Giuseppe/E-8297-2017;
OI Ottensmeier, Christian/0000-0003-3619-1657; Giaccone,
Giuseppe/0000-0002-5023-7562; Schuette, Wolfgang/0000-0002-7516-5649;
bearz, alessandra/0000-0003-1020-2338; MAZIERES,
JULIEN/0000-0002-5921-7613; benekli, mustafa/0000-0003-3184-4946
FU Agennix Inc.
FX This trial was funded by Agennix Inc.
NR 25
TC 21
Z9 22
U1 0
U2 13
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 2013
VL 24
IS 11
BP 2875
EP 2880
DI 10.1093/annonc/mdt371
PG 6
WC Oncology
SC Oncology
GA 247TF
UT WOS:000326643200029
PM 24050956
ER
PT J
AU Italiano, A
Le Cesne, A
Bellera, C
Piperno-Neumann, S
Duffaud, F
Penel, N
Cassier, P
Domont, J
Takebe, N
Kind, M
Coindre, JM
Blay, JY
Bui, B
AF Italiano, A.
Le Cesne, A.
Bellera, C.
Piperno-Neumann, S.
Duffaud, F.
Penel, N.
Cassier, P.
Domont, J.
Takebe, N.
Kind, M.
Coindre, J. -M.
Blay, J. -Y.
Bui, B.
TI GDC-0449 in patients with advanced chondrosarcomas: a French Sarcoma
Group/US and French National Cancer Institute Single-Arm Phase II
Collaborative Study
SO ANNALS OF ONCOLOGY
LA English
DT Article
DE chondrosarcoma; Hedgehog pathway; treatment; GDC-0449
ID ANTICANCER AGENTS; CHEMORESISTANCE; MUTATIONS; DESIGNS; TUMORS
AB Pre-clinical data have suggested a therapeutic role of Hedgehog (Hh) pathway inhibitors in chondrosarcoma.
This phase II trial included patients with progressive advanced chondrosarcoma. They received GDC-0449 150 mg/day (days 1-28, 28-day cycle). The primary end point was the 6-month clinical benefit rate (CBR) defined as the proportion of patients with non-progressive disease at 6 months. A 6-month CBR of 40% was considered as a reasonable objective to claim drug efficacy.
Between February 2011 and February 2012, 45 patients were included. Twenty had received prior chemotherapy. Thirty-nine were assessable for efficacy. The 6-month CBR was 25.6% (95% confidence interval 13.0-42.1). All stable patients had grade 1 or 2 conventional chondrosarcoma with documented progression within the 6 months before inclusion. All but one with available data also had overexpression of the Hh ligand. Median progression-free and overall survivals were 3.5 and 12.4 months, respectively. The most frequent adverse events were grade 1 or 2 myalgia, dysgeusia and alopecia.
GDC-0449 did not meet the primary end point of this trial. Results suggest some activity in a subset of patients with progressive grade 1 or 2 conventional chondrosarcoma. Further studies assessing its role in combination with chemotherapy are warranted.
NCT01267955.
C1 [Italiano, A.; Bui, B.] Inst Bergonie, Dept Med Oncol, Bordeaux, France.
[Le Cesne, A.; Domont, J.] Inst Gustave Roussy, Dept Med, Villejuif, France.
[Bellera, C.] Inst Bergonie, Clin & Epidemiol Res Unit, Bordeaux, France.
[Bellera, C.] CTD INCa, Data Ctr Canc Clin Trials, Bordeaux, France.
[Piperno-Neumann, S.] Inst Curie, Dept Med, Paris, France.
[Duffaud, F.] Hop Enfants La Timone, Dept Med Oncol, Marseille, France.
[Penel, N.] Ctr Oscar Lambret, Dept Med, F-59020 Lille, France.
[Cassier, P.] Ctr Leon Berard, Dept Med, F-69373 Lyon, France.
[Takebe, N.] Natl Canc Inst, Rockville, MD USA.
[Kind, M.] Inst Bergonie, Dept Radiol, Bordeaux, France.
[Coindre, J. -M.] Inst Bergonie, Dept Pathol, Bordeaux, France.
RP Italiano, A (reprint author), Inst Bergonie, Early Phase Trials Unit, 229 Cours Argonne, F-33076 Bordeaux, France.
EM a.italiano@bordeaux.unicancer.fr
RI Blay, Jean-Yves/N-3966-2016
OI Blay, Jean-Yves/0000-0001-7190-120X
FU French National Cancer Institute (INCa) [2009-342, INCa-DGOS-Inserm
6046]
FX French National Cancer Institute (INCa) (grant '2009-342' and grant
'INCa-DGOS-Inserm 6046').
NR 21
TC 13
Z9 13
U1 0
U2 3
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 2013
VL 24
IS 11
BP 2922
EP 2926
DI 10.1093/annonc/mdt391
PG 5
WC Oncology
SC Oncology
GA 247TF
UT WOS:000326643200037
PM 24170610
ER
PT J
AU Chung, H
Cho, H
Perry, C
Song, J
Ylaya, K
Lee, H
Kim, JH
AF Chung, Hyunsoo
Cho, Hanbyoul
Perry, Candice
Song, Jaekyung
Ylaya, Kris
Lee, Heejeong
Kim, Jae-Hoon
TI Downregulation of ERp57 expression is associated with poor prognosis in
early-stage cervical cancer
SO BIOMARKERS
LA English
DT Article
DE Cervical cancer; ERp57; immunohistochemistry; survival; tissue
microarray
ID CELL CARCINOMA; IMMUNE ESCAPE; TIME; COMPLEX
AB Objective: We investigated the clinical significance of ERp57 in the progression of cervical cancer.
Methods: mRNA and protein expression of ERp57 in cervical neoplasias were examined.
Results: ERp57 mRNA expression was significantly decreased in cervical cancers. Immunohistochemistry revealed that ERp57 expression in 123 cervical cancers was downregulated compared to cervical intraepithelial neoplasias or normal tissues (p<0.001). Low ERp57 expression was significantly associated with worse overall survival (HR = 12.19, p = 0.018).
Conclusions: Low ERp57 expression independently predicts a poor outcome for patients with cervical cancer, supporting the notion that ERp57 may be a promising novel cancer target.
C1 [Chung, Hyunsoo; Perry, Candice; Ylaya, Kris] NCI, Tissue Array Res Program, Pathol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
[Cho, Hanbyoul; Song, Jaekyung; Kim, Jae-Hoon] Yonsei Univ, Coll Med, Inst Womens Life Med Sci, Dept Obstet & Gynecol, Seoul 135720, South Korea.
[Lee, Heejeong] Catholic Univ Korea, Bucheon St Marys Hosp, Dept Pathol, Seoul, South Korea.
RP Kim, JH (reprint author), Yonsei Univ, Coll Med, Gangnam Severance Hosp, Dept Obstet & Gynecol, 146-92 Dogok Dong, Seoul 135720, South Korea.
EM heejung@catholic.ac.kr; jaehoonkim@yuhs.ac
FU National Research Foundation of Korea (NRF); Ministry of Education,
Science and Technology [2011-0005230, 2011-0010286, 2011-0007146];
Yonsei University College of Medicine [3-2010-0072, 6-2011-0073]
FX This work was supported in part by grants from the Basic Science
Research Program through the National Research Foundation of Korea (NRF)
funded by the Ministry of Education, Science and Technology
(2011-0005230, 2011-0010286, and 2011-0007146), and faculty research
grants from Yonsei University College of Medicine for 2010 and 2011
(3-2010-0072 and 6-2011-0073).
NR 17
TC 7
Z9 9
U1 0
U2 6
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1354-750X
EI 1366-5804
J9 BIOMARKERS
JI Biomarkers
PD NOV
PY 2013
VL 18
IS 7
BP 573
EP 579
DI 10.3109/1354750X.2013.827742
PG 7
WC Biotechnology & Applied Microbiology; Toxicology
SC Biotechnology & Applied Microbiology; Toxicology
GA 251EF
UT WOS:000326909900004
PM 23957851
ER
PT J
AU Ross, A
Sundaramurthi, T
Bevans, M
AF Ross, Alyson
Sundaramurthi, Thiruppavai
Bevans, Margaret
TI A Labor of Love The Influence of Cancer Caregiving on Health Behaviors
SO CANCER NURSING
LA English
DT Article
DE Burden; Cancer; Caregivers; Health behaviors; Screening; Stress
ID QUALITY-OF-LIFE; CAUSE-SPECIFIC MORTALITY; CORONARY-HEART-DISEASE;
FAMILY CAREGIVERS; PHYSICAL-ACTIVITY; CARDIOVASCULAR-DISEASE; INFORMAL
CAREGIVERS; ALCOHOL-CONSUMPTION; ALLOSTATIC LOAD; BREAST-CANCER
AB Background: Evidence suggests that emotional distress and objective demands of cancer caregiving are comparable to those of dementia caregiving, yet little research has focused on the physical health of cancer caregivers. Whether the stress leads directly to changes in health or whether the stress leads to changes in health behaviors, which in turn affect health, has not been systematically examined.
Objective: The objective of this study was to review the research literature regarding changes in health behaviors associated with caring for an individual with cancer.
Methods: Literature was reviewed from multiple databases including CINAHL (Cumulative Index to Nursing and Allied Health Literature), CINAHL Plus, PsycNET, PubMed, SCOPUS, EMBASE, and Web of Science. Key words included health behavior, health promotion, caregivers/caregiving, cancer/oncology, diet/nutrition, exercise/physical activity, stress management, smoking and alcohol. Studies were included if they involved informal adult caregivers and at least 1 behavior associated with a healthy lifestyle. Of the 866 studies identified, 8 met the criteria.
Results: Studies revealed conflicting information, with some suggesting deleterious changes in behaviors, whereas others found the changes protective.
Conclusions: The lack of uniformity of terminology and conflicting findings make it difficult to conclude the impact of the caregiving experience on the health behaviors of cancer caregivers. Something is placing caregivers at risk for illness and early death, but the mechanisms behind the risk and the role of unhealthy behaviors are not clear.
Implications for Practice: At a minimum, cancer caregivers should be screened for behavior changes and disease risk. Developing standardized measures for future research including controlled, longitudinal studies is needed.
C1 [Ross, Alyson; Sundaramurthi, Thiruppavai; Bevans, Margaret] NIH, Nursing & Patient Care Serv, Ctr Clin, Bethesda, MD 20892 USA.
RP Bevans, M (reprint author), NIH, Ctr Clin, Bldg 10,Room 2B13, Bethesda, MD 20892 USA.
EM mbevans@cc.nih.gov
FU Intramural NIH HHS [Z99 CL999999]
NR 57
TC 6
Z9 6
U1 4
U2 23
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0162-220X
EI 1538-9804
J9 CANCER NURS
JI Cancer Nurs.
PD NOV-DEC
PY 2013
VL 36
IS 6
BP 474
EP 483
DI 10.1097/NCC.0b013e3182747b75
PG 10
WC Oncology; Nursing
SC Oncology; Nursing
GA 246IR
UT WOS:000326532000016
PM 23132126
ER
PT J
AU Maunakea, AK
Chepelev, I
Cui, KR
Zhao, KJ
AF Maunakea, Alika K.
Chepelev, Iouri
Cui, Kairong
Zhao, Keji
TI Intragenic DNA methylation modulates alternative splicing by recruiting
MeCP2 to promote exon recognition
SO CELL RESEARCH
LA English
DT Article
DE MeCP2; splicing; chromatin; intragenic DNA methylation; epigenomics;
histone acetylation
ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; RETT-SYNDROME; PROTEIN MECP2;
CANCER-CELLS; HUMAN GENOME; CPG ISLANDS; SEQ; HYPERACETYLATION;
DEMETHYLATION; EPIGENETICS
AB Although the function of DNA methylation in gene promoter regions is well established in transcriptional repression, the function of the evolutionarily conserved widespread distribution of DNA methylation in gene body regions remains incompletely understood. Here, we show that DNA methylation is enriched in included alternatively spliced exons (ASEs), and that inhibition of DNA methylation results in aberrant splicing of ASEs. The methyl-CpG-binding protein MeCP2 is enriched in included ASEs, particularly those that are also highly methylated, and inhibition of DNA methylation disrupts specific targeting of MeCP2 to exons. Interestingly, ablation of MeCP2 results in increased histone acetylation and aberrant ASE-skipping events. We further show that inhibition of histone deacetylase (HDAC) activity leads to exon skipping that shows a highly significant degree of overlap with that caused by MeCP2 knockdown. Together, our data indicate that intragenic DNA methylation operates in exon definition to modulate alternative RNA splicing and can enhance exon recognition via recruitment of the multifunctional protein MeCP2, which thereby maintains local histone hypoacetylation through the subsequent recruitment of HDACs.
C1 [Maunakea, Alika K.; Chepelev, Iouri; Cui, Kairong; Zhao, Keji] NHLBI, Syst Biol Ctr, NIH, Bethesda, MD 20892 USA.
RP Zhao, KJ (reprint author), NHLBI, Syst Biol Ctr, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM zhaok@nhlbi.nih.gov
FU Intramural Research Program of the National Institutes of Health,
National Heart, Lung, and Blood Institute; UGSP, National Institutes of
Health
FX We thank Dr B Volgelstein (Johns Hopkins University) for providing
HCT116-WT and HCT116-DKO cells [17]. We also thank Dr R Nagarajan
(University of California, San Francisco) for ChIP-PCR primer sequences
of SNRPN and GABRB3 regions, and Qingsong Tang (NHLBI) for assistance
with GAII sequencing. The sequencing of RNA-Seq samples was performed by
the DNA Sequencing and Genomics Core facility of NHLBI. This work was
supported by the Intramural Research Program of the National Institutes
of Health, National Heart, Lung, and Blood Institute (KZ). AKM was
additionally supported by a fellowship from the UGSP, National
Institutes of Health.
NR 46
TC 149
Z9 155
U1 8
U2 43
PU INST BIOCHEMISTRY & CELL BIOLOGY
PI SHANGHAI
PA SIBS, CAS, 319 YUEYANG ROAD, SHANGHAI, 200031, PEOPLES R CHINA
SN 1001-0602
EI 1748-7838
J9 CELL RES
JI Cell Res.
PD NOV
PY 2013
VL 23
IS 11
BP 1256
EP 1269
DI 10.1038/cr.2013.110
PG 14
WC Cell Biology
SC Cell Biology
GA 248GE
UT WOS:000326683600008
PM 23938295
ER
PT J
AU Sun, Y
Li, Q
Gui, H
Xu, DP
Yang, YL
Su, DF
Liu, X
AF Sun, Yang
Li, Qi
Gui, Huan
Xu, Dong-Ping
Yang, Yi-Li
Su, Ding-Feng
Liu, Xia
TI MicroRNA-124 mediates the cholinergic anti-inflammatory action through
inhibiting the production of pro-inflammatory cytokines
SO CELL RESEARCH
LA English
DT Article
DE microRNA-124; cholinergic anti-inflammatory action; alpha 7nAChR;
macrophages; septic shock; STAT3; TACE
ID KAPPA-B-ZETA; VAGUS NERVE; NICOTINIC RECEPTOR; SIGNAL TRANSDUCER;
ENDOTOXIN-SHOCK; CUTTING EDGE; PATHWAY; ACETYLCHOLINE; CELLS; TNF
AB The vagus nerve can control inflammatory response through a 'cholinergic anti-inflammatory pathway', which is mediated by the alpha 7-nicotinic acetylcholine receptor (alpha 7nAChR) on macrophages. However, the intracellular mechanisms that link alpha 7nAChR activation and pro-inflammatory cytokine production remain not well understood. In this study, we found that miR-124 is upregulated by cholinergic agonists in LPS-exposed cells and mice. Utilizing miR-124 mimic and siRNA knockdown, we demonstrated that miR-124 is a critical mediator for the cholinergic anti-inflammatory action. Furthermore, our data indicated that miR-124 modulates LPS-induced cytokine production by targeting signal transducer and activator of transcription 3 (STAT3) to decrease IL-6 production and TNF-alpha converting enzyme (TACE) to reduce TNF-alpha release. These results also indicate that miR-124 is a potential therapeutic target for the treatment of inflammatory diseases.
C1 [Sun, Yang; Li, Qi; Gui, Huan; Xu, Dong-Ping; Su, Ding-Feng; Liu, Xia] Second Mil Med Univ, Sch Pharm, Dept Pharmacol, Shanghai 200433, Peoples R China.
[Yang, Yi-Li] NCI, Canc & Dev Biol Lab, NIH, Frederick, MD 21702 USA.
RP Liu, X (reprint author), Second Mil Med Univ, Sch Pharm, Dept Pharmacol, Shanghai 200433, Peoples R China.
EM yiliyang@mail.nih.gov; dfsu2008@gmail.com; lxflying@aliyun.com
FU National Key Basic Research Program of China (973 Program)
[2009CB521901]; National Natural Science Foundation of China [30973525,
81273606]
FX We thank Dr Alan O Perantoni (National Institutes of Health, USA) for
critical reading of the manuscript, and Dr Luis G Rodriguez for the
STAT3-/- MEFs. This work was supported by the National Key
Basic Research Program of China (973 Program; 2009CB521901 to Ding-Feng
Su) and the National Natural Science Foundation of China (30973525 and
81273606 to Xia Liu).
NR 51
TC 39
Z9 41
U1 3
U2 23
PU INST BIOCHEMISTRY & CELL BIOLOGY
PI SHANGHAI
PA SIBS, CAS, 319 YUEYANG ROAD, SHANGHAI, 200031, PEOPLES R CHINA
SN 1001-0602
EI 1748-7838
J9 CELL RES
JI Cell Res.
PD NOV
PY 2013
VL 23
IS 11
BP 1270
EP 1283
DI 10.1038/cr.2013.116
PG 14
WC Cell Biology
SC Cell Biology
GA 248GE
UT WOS:000326683600009
PM 23979021
ER
PT J
AU Comlekoglu, DU
Thompson, IA
Sen, HN
AF Comlekoglu, Didar U.
Thompson, Ian A.
Sen, H. Nida
TI Autoimmune retinopathy
SO CURRENT OPINION IN OPHTHALMOLOGY
LA English
DT Review
DE anti-retinal autoantibodies; autoimmune retinopathy; cancer-associated
retinopathy; immunosuppression; melanoma-associated retinopathy;
recoverin; uveitis
ID CANCER-ASSOCIATED RETINOPATHY; MELANOMA-ASSOCIATED RETINOPATHY;
ANTI-RETINAL ANTIBODIES; PARANEOPLASTIC RETINOPATHY; BIPOLAR CELLS;
PHOTORECEPTOR DEGENERATION; ANTIRETINAL ANTIBODIES; MALIGNANT-MELANOMA;
ALPHA-ENOLASE; CAR SYNDROME
AB Purpose of reviewAutoimmune retinopathy (AIR) is an immune-mediated disorder characterized by progressive visual loss, abnormal electroretinographic and visual field findings in the presence of circulating anti-retinal antibodies. This review highlights advances made toward understanding the pathophysiology, clinical manifestations, and trends in the management of AIR.Recent findingsThe pathophysiology of AIR is likely antibody-mediated. AIR serum autoantibodies are variable in their size and retinal tissue they target and can also be present in healthy controls and multiple autoimmune diseases. Rarely, AIR may be associated with dysregulated self-tolerance mechanisms in the thymus. Despite progress in research, our understanding of AIR remains incomplete. Lack of standardized methods for anti-retinal antibody testing continues to challenge the interpretation of seropositivity. Conventional immunosuppressives have been further studied, and promising immunomodulatory therapies, such as targeted B-cell therapy, have been introduced. Newer imaging modalities such as fundus autofluorescence and spectral domain optical coherence tomography may be helpful in diagnosis, monitoring progression of disease and response to treatment.SummaryAIR is a rare but vision-threatening disease whose pathogenesis is poorly defined. Lack of standardized clinical or laboratory criteria further complicates the diagnosis and management. Despite recent progress, further basic science research into the autoimmune process is needed. Prospective controlled clinical trials with immunomodulatory therapy can help define future treatment paradigms
C1 [Comlekoglu, Didar U.; Thompson, Ian A.; Sen, H. Nida] NEI, NIH, Bethesda, MD 20892 USA.
RP Comlekoglu, DU (reprint author), NEI, NIH, 10 Ctr Dr,10-10N109, Bethesda, MD 20892 USA.
EM senh@nei.nih.gov
OI Comlekoglu, Erhan/0000-0002-0915-5821
FU National Eye Institute's Intramural Research Program
FX None of the authors have any conflicts of interest. This research is
supported by the National Eye Institute's Intramural Research Program.
NR 74
TC 3
Z9 3
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1040-8738
EI 1531-7021
J9 CURR OPIN OPHTHALMOL
JI Curr. Opin. Ophthalmol.
PD NOV
PY 2013
VL 24
IS 6
BP 598
EP 605
DI 10.1097/ICU.0b013e3283654e1e
PG 8
WC Ophthalmology
SC Ophthalmology
GA 247BL
UT WOS:000326588500011
PM 24100366
ER
PT J
AU Samsel, L
Dagur, PK
Raghavachari, N
Seamon, C
Kato, GJ
McCoy, JP
AF Samsel, Leigh
Dagur, Pradeep K.
Raghavachari, Nalini
Seamon, Catherine
Kato, Gregory J.
McCoy, J. Philip, Jr.
TI Imaging Flow Cytometry for Morphologic and Phenotypic Characterization
of Rare Circulating Endothelial Cells
SO CYTOMETRY PART B-CLINICAL CYTOMETRY
LA English
DT Article
DE circulating endothelial cells; imaging cytometry; rare event cytometry
ID METASTATIC CARCINOMAS; PERIPHERAL-BLOOD
AB Endothelial cells in the peripheral circulation are rare events that require technically rigorous approaches for detection by flow cytometry. Visualization of these cells has been even more demanding, as this has historically required extensive enrichment and processing prior to attempting imaging. As a result, few, if any, examples exist on images of peripheral blood circulating endothelial cells (CECs) that include verification of the cell lineage both phenotypically and genomically. In this study, we have devised a method whereby CECs can be directly visualized after lysis of red blood cells and staining, without pre-enrichment or additional processing. Peripheral blood is stained with CD45, CD146, CD3, Hoechst, and DAPI to permit identification of CD146 positive, nonleukocyte, nucleated, and live cells that fit the description of CECs. These cells are imaged using the Amnis ImageStream(X), an imaging flow cytometer. Genomic verification of the endothelial nature of these cells is accomplished by using an aliquot of the same stained samples for sorting CECs using similar gating strategies. This proof of principle of direct imaging of CECs by imaging flow cytometry will permit studies to be conducted heretofore not possible, as the ImageStream(X) has the capability of detecting additional fluorochromes other than those used to identify the CECs. Such potential investigations include antigen colocalization or capping, autophagy and apoptosis, morphologic changes in response to therapy, and others. Thus, this method will enable a broad range of novel studies to be conducted using CECs as surrogates of the endothelium. Published 2013 Wiley-Periodicals, Inc.-/- mice. We also thank J. Wood for Nav1.8-cre mice, C.
Pritchard and R. Marais for Brafv650E mice, and Q. Liu, M.
Jacquin, G. Giesler, and lab members for comments. J. Jeffry has been
supported by a NIDA training grant. The research was supported by RO1
grants from the National Institute of Arthritis and Musculoskeletal and
Skin Diseases to Z.-F. Chen (RO1 AR056318-01A1) and the National Eye
Institute (1R01EY022409 and administrative supplement
3R01EY022409-01S1), the Whitehall Foundation (2010-08-61) to J. Zhong,
and a NIH RO1 grant to R. Kopan (R01DK066408).
NR 60
TC 26
Z9 26
U1 2
U2 21
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 2013
VL 123
IS 11
BP 4769
EP 4780
DI 10.1172/JCI70528
PG 12
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 247IU
UT WOS:000326611900024
PM 24216512
ER
PT J
AU Stewart, CA
Metheny, H
Iida, N
Smith, L
Hanson, M
Steinhagen, F
Leighty, RM
Roers, A
Karp, CL
Muller, W
Trinchieri, G
AF Stewart, C. Andrew
Metheny, Hannah
Iida, Noriho
Smith, Loretta
Hanson, Miranda
Steinhagen, Folkert
Leighty, Robert M.
Roers, Axel
Karp, Christopher L.
Mueller, Werner
Trinchieri, Giorgio
TI Interferon-dependent IL-10 production by Tregs limits tumor Th17
inflammation
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Article
ID REGULATORY T-CELLS; PERSISTENT LCMV INFECTION; I INTERFERON; DENDRITIC
CELLS; C-MAF; INTERLEUKIN-10-DEFICIENT MICE; ESTABLISHED MELANOMA;
IMMUNE SURVEILLANCE; CYTOKINE PRODUCTION; VIRAL-INFECTION
AB The capacity of IL-10 and Tregs in the inflammatory tumor microenvironment to impair anticancer Th1 immunity makes them attractive targets for cancer immunotherapy. IL-10 and Tregs also suppress Th17 activity, which is associated with poor prognosis in several cancers. However, previous studies have overlooked their potential contribution to the regulation of pathogenic cancer-associated inflammation. In this study, we investigated the origin and function of IL-10-producing cells in the tumor microenvironment using transplantable tumor models in mice. The majority of tumor-associated IL-10 was produced by an activated Treg population. IL-10 production by Tregs was required to restrain Th17-type inflammation. Accumulation of activated IL-10+ Tregs in the tumor required type I IFN signaling but not inflammatory signaling pathways that depend on TLR adapter protein MyD88 or IL-12 family cytokines. IL-10 production limited Th17 cell numbers in both spleen and tumor. However, type I IFN was required to limit Th17 cells specifically in the tumor microenvironment, reflecting selective control of tumor-associated Tregs by type I IFN. Thus, the interplay of type I IFN, Tregs, and IL-10 is required to negatively regulate Th17 inflammation in the tumor microenvironment. Therapeutic interference of this network could therefore have the undesirable consequence of promoting Th17 inflammation and cancer growth.
C1 [Stewart, C. Andrew; Metheny, Hannah; Iida, Noriho; Smith, Loretta; Hanson, Miranda; Steinhagen, Folkert; Trinchieri, Giorgio] NCI, Canc & Inflammat Program, Ctr Canc Res, NIH, Frederick, MD 21702 USA.
[Steinhagen, Folkert] Univ Hosp Bonn, Dept Anesthesiol & Intens Care Med, Bonn, Germany.
[Leighty, Robert M.] Data Management Serv Inc, Frederick Natl Lab Canc Res, Frederick, MD USA.
[Roers, Axel] Tech Univ Dresden, Med Fac Carl Gustav Carus, Dresden, Germany.
[Karp, Christopher L.] Cincinnati Childrens Hosp Res Fdn, Div Mol Immunol, Cincinnati, OH USA.
[Mueller, Werner] Univ Manchester, Fac Life Sci, Bill Ford Chair Cellular Immunol, Manchester, Lancs, England.
RP Trinchieri, G (reprint author), NCI, Canc & Inflammat Program, Ctr Canc Res, NIH, Bldg 560 Room 31-93, Frederick, MD 21702 USA.
EM trinchig@mail.nih.gov
RI Stewart, Charles/G-2470-2012; Muller, Werner/B-9044-2008
OI Muller, Werner/0000-0002-1297-9725
FU National Cancer Institute, NIH (NCI/NIH) [HHSN261200800001E]
FX We wish to thank Dragana Jankovic, Yasmine Belkaid, Amiran Dzutsev,
Romina Goldszmid, Marco Cardone, Elena Riboldi, Rosalba Salcedo, Xin
Chen, Cristina Bergamaschi, Howard Young, and Andy Hurwitz for their
insight and discussion. We thank Robin Winkler-Pickett and Tim Back for
expert technical assistance. We are very grateful to Kathleen Noer and
Roberta Matthai of the Cancer and Inflammation Program Flow Cytometry
Core for assistance with flow sorting. We also thank Bob Jack, Brian
Kelsall, Christian Schindler, Vijay Kuchroo, David Levy, Michel Aguet,
Sergei Nedospasov, Shizuo Akira, Christian Saris, and Amgen Inc. for
their kind provision of mice. This work was supported by the Intramural
Research Program of the National Cancer Institute, NIH (NCI/NIH) 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 100
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Z9 46
U1 1
U2 21
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 2013
VL 123
IS 11
BP 4859
EP 4874
DI 10.1172/BCI65180
PG 16
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 247IU
UT WOS:000326611900032
PM 24216477
ER
PT J
AU Roy, S
Ryals, MM
Van den Bruele, AB
Fitzgerald, TS
Cunningham, LL
AF Roy, Soumen
Ryals, Matthew M.
Van den Bruele, Astrid Botty
Fitzgerald, Tracy S.
Cunningham, Lisa L.
TI Sound preconditioning therapy inhibits ototoxic hearing loss in mice
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Article
ID HAIR CELL-DEATH; CISPLATIN-INDUCED OTOTOXICITY; HEAT-SHOCK; THRESHOLD
SHIFT; HSP70; RATS; CHEMOTHERAPY; PROTECTION; STRESS; INJURY
AB Therapeutic drugs with ototoxic side effects cause significant hearing loss for thousands of patients annually. Two major classes of ototoxic drugs are cisplatin and the aminoglycoside antibiotics, both of which are toxic to mechanosensory hair cells, the receptor cells of the inner ear. A critical need exists for therapies that protect the inner ear without inhibiting the therapeutic efficacy of these drugs. The induction of heat shock proteins (HSPs) inhibits both aminoglycoside- and cisplatin-induced hair cell death and hearing loss. We hypothesized that exposure to sound that is titrated to stress the inner ear without causing permanent damage would induce HSPs in the cochlea and inhibit ototoxic drug-induced hearing loss. We developed a sound exposure protocol that induces HSPs without causing permanent hearing loss. We used this protocol in conjunction with a newly developed mouse model of cisplatin ototoxicity and found that preconditioning mouse inner ears with sound has a robust protective effect against cisplatin-induced hearing loss and hair cell death. Sound therapy also provided protection against aminoglycoside-induced hearing loss. These data indicate that sound preconditioning protects against both classes of ototoxic drugs, and they suggest that sound therapy holds promise for preventing hearing loss in patients receiving these drugs.
C1 [Roy, Soumen; Ryals, Matthew M.; Van den Bruele, Astrid Botty; Fitzgerald, Tracy S.; Cunningham, Lisa L.] Natl Inst Deafness & Other Commun Disorders NIDCD, NIH, Rockville, MD USA.
RP Cunningham, LL (reprint author), Natl Inst Deafness & Other Commun Disorders, NIH, 5 Res Ct, Rockville, MD 20850 USA.
EM Lisa.cunningham@nih.gov
FU NIH/NIDCD [ZIA DC 000079]
FX This work was supported by the NIH/NIDCD Division of Intramural Research
(ZIA DC 000079). The authors thank Su-Hua Sha, Mark Warchol, Nicole
Schmitt, and Tiffany Baker for their insightful discussions about mouse
models of cisplatin ototoxicity. We are indebted to Donnie Catts and the
NIDCD veterinary staff for their excellent animal care. Our thanks to
Dennis Drayna, Thomas Friedman, Andrew Griffith, and Carter VanWaes for
their helpful comments on the manuscript.
NR 29
TC 17
Z9 17
U1 1
U2 10
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 2013
VL 123
IS 11
BP 4945
EP 4949
DI 10.1172/JCI71353
PG 5
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 247IU
UT WOS:000326611900040
PM 24216513
ER
PT J
AU Goyama, S
Schibler, J
Cunningham, L
Zhang, Y
Rao, Y
Nishimoto, N
Nakagawa, M
Olsson, A
Wunderlich, M
Link, KA
Mizukawa, B
Grimes, HL
Kurokawa, M
Liu, PP
Huang, G
Mulloy, JC
AF Goyama, Susumu
Schibler, Janet
Cunningham, Lea
Zhang, Yue
Rao, Yalan
Nishimoto, Nahoko
Nakagawa, Masahiro
Olsson, Andre
Wunderlich, Mark
Link, Kevin A.
Mizukawa, Benjamin
Grimes, H. Leighton
Kurokawa, Mineo
Liu, P. Paul
Huang, Gang
Mulloy, James C.
TI Transcription factor RUNX1 promotes survival of acute myeloid leukemia
cells (vol 123, pg 3876, 2013)
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Correction
C1 [Goyama, Susumu; Schibler, Janet; Zhang, Yue; Rao, Yalan; Wunderlich, Mark; Link, Kevin A.; Mizukawa, Benjamin; Grimes, H. Leighton; Huang, Gang; Mulloy, James C.] Univ Cincinnati, Coll Med, Cincinnati Childrens Hosp Med Ctr, Div Expt Hematol & Canc Biol, Cincinnati, OH 45221 USA.
[Cunningham, Lea; Liu, P. Paul] NHGRI, Oncogenesis & Dev Sect, NIH, Bethesda, MD 20892 USA.
[Nishimoto, Nahoko; Nakagawa, Masahiro; Kurokawa, Mineo] Univ Tokyo, Grad Sch Med, Dept Hematol & Oncol, Tokyo, Japan.
[Olsson, Andre; Grimes, H. Leighton] Cincinnati Childrens Hosp Med Ctr, Div Immunobiol, Cincinnati, OH 45229 USA.
RP Goyama, S (reprint author), Univ Cincinnati, Coll Med, Cincinnati Childrens Hosp Med Ctr, Div Expt Hematol & Canc Biol, Cincinnati, OH 45221 USA.
RI Liu, Paul/A-7976-2012
OI Liu, Paul/0000-0002-6779-025X
NR 1
TC 2
Z9 2
U1 0
U2 4
PU AMER SOC CLINICAL INVESTIGATION INC
PI ANN ARBOR
PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA
SN 0021-9738
EI 1558-8238
J9 J CLIN INVEST
JI J. Clin. Invest.
PD NOV
PY 2013
VL 123
IS 11
BP 4979
EP 4979
DI 10.1172/JCI73313
PG 1
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 247IU
UT WOS:000326611900048
ER
PT J
AU Killian, MS
Teque, F
Walker, RL
Meltzer, PS
Killian, JK
AF Killian, M. Scott
Teque, Fernando
Walker, Robert L.
Meltzer, Paul S.
Killian, J. Keith
TI CD8(+) Lymphocytes Suppress Human Immunodeficiency Virus 1 Replication
by Secreting Type I Interferons
SO JOURNAL OF INTERFERON AND CYTOKINE RESEARCH
LA English
DT Article
ID ANTI-HIV RESPONSE; LONG TERMINAL REPEAT; CD8+ T-CELLS; ANTIVIRAL FACTOR;
BETA-CHEMOKINES; GENE-EXPRESSION; ANTIRETROVIRAL THERAPY; INFECTED
INDIVIDUALS; ANTI-HIV-1 ACTIVITY; ALPHA PRODUCTION
AB CD8(+) cells can suppress human immunodeficiency virus 1 (HIV-1) replication by releasing soluble factors. In 26 years of intensive research efforts, the identity of the major CD8(+) cell antiviral factor has remained elusive. To investigate the mechanism for this antiviral immune response, we performed gene expression analyses on primary CD4(+) cells that were exposed to HIV-suppressing CD8(+) cells or CD8(+) cell-conditioned medium having HIV-suppressing activity. These experiments revealed increased levels of multiple genes stimulated by type I interferons (IFN; eg, IFN- and IFN-). Further evaluation revealed that primary CD8(+) cells, particularly those from elite controllers and other asymptomatic HIV-1-infected individuals, secrete IFN, and this response directly contributes to the in vitro suppression of HIV replication in CD4(+) cells. This novel immune response, likely mediated by memory CD8(+) T cells, may play an important role in a wide variety of viral infections, cancers, and autoimmune diseases.
C1 [Killian, M. Scott; Teque, Fernando] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA.
[Walker, Robert L.; Meltzer, Paul S.; Killian, J. Keith] NCI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA.
RP Killian, MS (reprint author), Univ Calif San Francisco, Dept Med, 513 Parnassus Ave, San Francisco, CA 94143 USA.
EM m.scott.killian@gmail.com
FU National Institutes of Health [3P30AI027763-19S2]; California HIV/AIDS
Research Program [ID09-SF-058]; NIH National Cancer Institute
FX This research was funded by grants from the National Institutes of
Health (3P30AI027763-19S2) and the California HIV/AIDS Research Program
(ID09-SF-058) and was supported in part by the Intramural Research
Program of the NIH National Cancer Institute.
NR 65
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U1 0
U2 5
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 2013
VL 33
IS 11
BP 632
EP 645
DI 10.1089/jir.2012.0067
PG 14
WC Biochemistry & Molecular Biology; Cell Biology; Immunology
SC Biochemistry & Molecular Biology; Cell Biology; Immunology
GA 242KA
UT WOS:000326238100002
PM 23402527
ER
PT J
AU Doyle, TA
de Groot, M
Harris, T
Schwartz, F
Strotmeyer, ES
Johnson, KC
Kanaya, A
AF Doyle, Todd A.
de Groot, Mary
Harris, Tamara
Schwartz, Frank
Strotmeyer, Elsa S.
Johnson, Karen C.
Kanaya, Alka
TI Diabetes, depressive symptoms, and inflammation in older adults: Results
from the Health, Aging, and Body Composition Study
SO JOURNAL OF PSYCHOSOMATIC RESEARCH
LA English
DT Article
DE Diabetes; Depressive symptoms; Inflammation; Interleukin-6; Tumor
necrosis factor-alpha; C-reactive protein
ID C-REACTIVE PROTEIN; TUMOR-NECROSIS-FACTOR; LOW-GRADE INFLAMMATION;
CELL-ADHESION MOLECULES; CORONARY-HEART-DISEASE; ACUTE-PHASE REACTANTS;
FACTOR-ALPHA LEVELS; SCALE CES-D; INSULIN-RESISTANCE; ENDOTHELIAL
DYSFUNCTION
AB Objective: Up-regulated levels of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and C-reactive protein (CRP) are common to both type 2 diabetes mellitus (T2DM) and elevated depressive symptoms, yet little attention has been given to the biological mechanisms associated with these co-morbidities. This study examined the association between inflammation and both T2DM and elevated depressive symptoms.
Methods: Baseline data were analyzed from 3009 adults, aged 70-79, participating in the Health, Aging, and Body Composition Study. Diabetes was assessed per self-report, medication use, fasting glucose and/or glucose tolerance tests. Elevated depressive symptoms were categorized using the Center for Epidemiologic Studies Depression scale (cut-score >= 20). Log-transformed IL-6, TNF-alpha, and CRP were analyzed using ANCOVA.
Results: Participants with T2DM and elevated depressive symptoms (T2DM + DEP n = 14) demonstrated significantly (p < .05) higher IL-6 compared to (T2DM Only n = 628), (DEP Only n = 49), and (No T2DM or DEP n = 2067) groups following covariate adjustment. Similarly, participants with T2DM + DEP (n = 14) had significantly (p < .05) higher CRP, after covariate adjustment, compared to DEP Only (n = 50) and No T2DM or DEP groups (n = 2153). No association was observed for TNF-alpha.
Conclusions: These findings provide evidence that inflammation is associated with T2DM and elevated depressive symptoms. Participants with T2DM + DEP demonstrated the highest IL-6 levels compared to all other groups. Greater CRP levels were also observed in T2DM, but not elevated depressive symptoms, which may suggest that differential associations between T2DM and depressive symptoms exist for various inflammatory markers. Further investigation into these associations could aid in understanding the biological pathways underlying both T2DM and depressive symptoms. (C) 2013 Elsevier Inc. All rights reserved.
C1 [Doyle, Todd A.] Ohio Univ, Dept Psychol, Athens, OH 45701 USA.
[de Groot, Mary] Indiana Univ, Sch Med, Indianapolis, IN USA.
[Harris, Tamara] NIA, Epidemiol Demog & Biometry Program, Bethesda, MD 20892 USA.
[Schwartz, Frank] Ohio Univ, Inst Diabet, Heritage Coll Osteopath Med, Athens, OH 45701 USA.
[Strotmeyer, Elsa S.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA.
[Johnson, Karen C.] Univ Tennessee, Ctr Hlth Sci, Dept Prevent Med, Memphis, TN 38163 USA.
[Kanaya, Alka] Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94143 USA.
RP Doyle, TA (reprint author), Loyola Univ, Med Ctr, Dept Psychiat & Behav Neurosci, 2160 S 1st Ave, Maywood, IL 60153 USA.
EM todddoyle1@lumc.edu
RI Strotmeyer, Elsa/F-3015-2014;
OI Strotmeyer, Elsa/0000-0002-4093-6036
FU Intramural Research Program of the NIH; National Institute on Aging
(NIA) [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106, R01-AG028050]; NINR
[R01-NR012459]; NIDDK [R34DK071545, R18DK092765]; Ohio University
Diabetes Research Initiative
FX This research was supported by the Intramural Research Program of the
NIH, the National Institute on Aging (NIA), and the NIA Contracts
N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106, NIA grant R01-AG028050,
NINR grant R01-NR012459, NIDDK R34DK071545 and NIDDK R18DK092765. The
authors would also like to thank the Ohio University Diabetes Research
Initiative for their support of this project.
NR 62
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U1 4
U2 15
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0022-3999
EI 1879-1360
J9 J PSYCHOSOM RES
JI J. Psychosomat. Res.
PD NOV
PY 2013
VL 75
IS 5
BP 419
EP 424
DI 10.1016/j.jpsychores.2013.08.006
PG 6
WC Psychiatry
SC Psychiatry
GA 248NZ
UT WOS:000326709500004
PM 24182629
ER
PT J
AU Weyant, RJ
Tracy, SL
Anselmo, T
Beltran-Aguilar, ED
Donly, KJ
Frese, WA
Hujoel, PP
Iafolla, T
Kohn, W
Kumar, J
Levy, SM
Tinanoff, N
Wright, JT
Zero, D
Aravamudhan, K
Frantsve-Hawley, J
Meyer, DM
AF Weyant, Robert J.
Tracy, Sharon L.
Anselmo, Theresa (Tracy)
Beltran-Aguilar, Eugenio D.
Donly, Kevin J.
Frese, William A.
Hujoel, Philippe P.
Iafolla, Timothy
Kohn, William
Kumar, Jayanth
Levy, Steven M.
Tinanoff, Norman
Wright, J. Timothy
Zero, Domenick
Aravamudhan, Krishna
Frantsve-Hawley, Julie
Meyer, Daniel M.
CA Amer Dent Assoc Council Sci
TI Topical fluoride for caries prevention Executive summary of the updated
clinical recommendations and supporting systematic review
SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION
LA English
DT Article
DE Caries prevention; caries; evidence-based dentistry; fluoride; practice
guidelines; preventive dentistry
ID ACIDULATED PHOSPHATE-FLUORIDE; RANDOMIZED CONTROLLED-TRIAL;
DENTAL-CARIES; VARNISH DURAPHAT; PRESCHOOL-CHILDREN; APPROXIMAL CARIES;
PRIMARY TEETH; ROOT CARIES; PROFESSIONAL APPLICATION; PROPHYLACTIC PASTE
AB Background. A panel of experts convened by the American Dental Association (ADA) Council on Scientific Affairs presents evidence-based clinical recommendations regarding professionally applied and prescription-strength, home-use topical fluoride agents for caries prevention. These recommendations are an update of the 2006 ADA recommendations regarding professionally applied topical fluoride and were developed by using a new process that includes conducting a systematic review of primary studies.
Types of Studies Reviewed. The authors conducted a search of MEDLINE and the Cochrane Library for clinical trials of professionally applied and prescription-strength topical fluoride agents-including mouthrinses, varnishes, gels, foams and pastes-with caries increment outcomes published in English through October 2012.
Results. The panel included 71 trials from 82 articles in its review and assessed the efficacy of various topical fluoride caries-preventive agents. The panel makes recommendations for further research.
Practical Implications. The panel recommends the following for people at risk of developing dental caries: 2.26 percent fluoride varnish or 1.23 percent fluoride (acidulated phosphate fluoride) gel, or a prescription-strength, home-use 0.05 percent fluoride gel or paste or 0.09 percent fluoride mouthrinse for patients 6 years or older. Only 2.26 percent fluoride varnish is recommended for children younger than 6 years. The strengths of the recommendations for the recommended products varied from "in favor" to "expert opinion for." As part of the evidence-based approach to care, these clinical recommendations should be integrated with the practitioner's professional judgment and the patient's needs and preferences.
C1 [Weyant, Robert J.] Univ Pittsburgh, Dept Dent Publ Hlth, Sch Dent Med, Pittsburgh, PA 15260 USA.
[Tracy, Sharon L.] Amer Dent Assoc, Div Sci, Ctr Evidence Based Dent, Chicago, IL 60611 USA.
[Anselmo, Theresa (Tracy)] San Luis Obispo Hlth Agcy, Oral Hlth Program, San Luis Obispo, CA USA.
[Beltran-Aguilar, Eugenio D.] Ctr Dis Control & Prevent, Div Oral Hlth, Atlanta, GA USA.
[Donly, Kevin J.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA.
[Frese, William A.] Univ Illinois, Dept Pediat, Chicago, IL USA.
[Hujoel, Philippe P.] Univ Washington, Sch Dent, Dept Dent Publ Hlth Sci, Seattle, WA 98195 USA.
[Iafolla, Timothy] Natl Inst Dent & Craniofacial Res, Off Sci Policy & Anal, NIH, Bethesda, MD USA.
[Kohn, William] Delta Dent Plans Assoc, Oak Brook, IL USA.
[Kumar, Jayanth] New York State Dept Hlth, Bur Dent Hlth, Albany, NY 12237 USA.
[Kumar, Jayanth] SUNY Albany, Sch Publ Hlth, Albany, NY 12222 USA.
[Levy, Steven M.] Univ Iowa, Coll Dent, Dept Prevent & Community Dent, Iowa City, IA 52242 USA.
[Levy, Steven M.] Univ Iowa, Dept Epidemiol, Coll Publ Hlth, Iowa City, IA USA.
[Tinanoff, Norman] Univ Maryland, Sch Dent, Baltimore, MD 21201 USA.
[Wright, J. Timothy] Univ N Carolina, Sch Dent, Dept Pediat Dent, Chapel Hill, NC USA.
[Zero, Domenick] Indiana Univ Sch Dent, Dept Prevent & Community Dent, Indianapolis, IN USA.
[Zero, Domenick] Indiana Univ Sch Dent, Oral Hlth Res Inst, Indianapolis, IN USA.
[Zero, Domenick] Indiana Univ Sch Dent, Indianapolis, IN USA.
[Aravamudhan, Krishna] Amer Dent Assoc, Div Dent Practice, Off Qual Assessment & Improvement, Chicago, IL USA.
[Frantsve-Hawley, Julie] Amer Dent Assoc, Div Sci, Ctr Evidence Based Dent, Chicago, IL USA.
[Meyer, Daniel M.] Amer Dent Assoc, Chicago, IL USA.
RP Tracy, SL (reprint author), Amer Dent Assoc, Div Sci, Ctr Evidence Based Dent, 211 E Chicago Ave, Chicago, IL 60611 USA.
EM tracys@ada.org
FU Centers for Disease Control and Prevention, Atlanta
FX The American Dental Association Council on Scientific Affairs Expert
Panel on Topical Fluoride Agents commissioned this study, which was
supported in part by the Centers for Disease Control and Prevention,
Atlanta. The findings and conclusions in this report are those of the
authors and do not necessarily represent the official position of the
Centers for Disease Control and Prevention.
NR 96
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U1 3
U2 16
PU AMER DENTAL ASSOC
PI CHICAGO
PA 211 E CHICAGO AVE, CHICAGO, IL 60611 USA
SN 0002-8177
EI 1943-4723
J9 J AM DENT ASSOC
JI J. Am. Dent. Assoc.
PD NOV
PY 2013
VL 144
IS 11
BP 1279
EP 1291
PG 13
WC Dentistry, Oral Surgery & Medicine
SC Dentistry, Oral Surgery & Medicine
GA 246DF
UT WOS:000326516600012
PM 24177407
ER
PT J
AU Povsic, TJ
Najjar, SS
Prather, K
Zhou, JY
Adams, SD
Zavodni, KL
Kelly, F
Melton, LG
Hasselblad, V
Heitner, JF
Raman, SV
Barsness, GW
Patel, MR
Kim, RJ
Lakatta, EG
Harrington, RA
Rao, SV
AF Povsic, Thomas J.
Najjar, Samer S.
Prather, Kristi
Zhou, Jiying
Adams, Stacie D.
Zavodni, Katherine L.
Kelly, Francine
Melton, Laura G.
Hasselblad, Vic
Heitner, John F.
Raman, Subha V.
Barsness, Gregory W.
Patel, Manesh R.
Kim, Raymond J.
Lakatta, Edward G.
Harrington, Robert A.
Rao, Sunil V.
TI EPC mobilization after erythropoietin treatment in acute ST-elevation
myocardial infarction: the REVEAL EPC substudy
SO JOURNAL OF THROMBOSIS AND THROMBOLYSIS
LA English
DT Article
DE Erythropoietin; Endothelial progenitor cells; Myocardial infarction;
Cryopreservation
ID ENDOTHELIAL PROGENITOR CELLS; ALDEHYDE DEHYDROGENASE-ACTIVITY;
RECOMBINANT-HUMAN-ERYTHROPOIETIN; PERIPHERAL-BLOOD; THERAPY; TRIAL
AB Erythropoietin (EPO) was hypothesized to mitigate reperfusion injury, in part via mobilization of endothelial progenitor cells (EPCs). The REVEAL trial found no reduction in infarct size with a single dose of EPO (60,000 U) in patients with ST-segment elevation myocardial infarction. In a substudy, we aimed to determine the feasibility of cryopreserving and centrally analyzing EPC levels to assess the relationship between EPC numbers, EPO administration, and infarct size. As a prespecified substudy, mononuclear cells were locally cryopreserved before as well as 24 and 48-72 h after primary percutaneous coronary intervention. EPC samples were collected in 163 of 222 enrolled patients. At least one sample was obtained from 125 patients, and all three time points were available in 83 patients. There were no significant differences in the absolute EPC numbers over time or between EPO- and placebo-treated patients; however, there was a trend toward a greater increase in EPC levels from 24 to 48-72 h postintervention in patients receiving a parts per thousand yen30,000 U of EPO (P = 0.099 for CD133(+) cells, 0.049 for CD34(+) cells, 0.099 for ALDH(br) cells). EPC numbers at baseline were inversely related to infarct size (P = 0.03 for CD133(+) cells, 0.006 for CD34(+) cells). Local whole cell cryopreservation and central EPC analysis in the context of a multicenter randomized trial is feasible but challenging. High-dose (a parts per thousand yen30,000 U) EPO may mobilize EPCs at 48-72 h, and baseline EPC levels may be inversely associated with infarct size.
C1 [Povsic, Thomas J.; Prather, Kristi; Melton, Laura G.; Hasselblad, Vic; Patel, Manesh R.; Harrington, Robert A.; Rao, Sunil V.] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC 27710 USA.
[Povsic, Thomas J.; Zhou, Jiying; Adams, Stacie D.; Zavodni, Katherine L.; Kelly, Francine; Patel, Manesh R.; Kim, Raymond J.; Harrington, Robert A.; Rao, Sunil V.] Duke Univ, Sch Med, Div Cardiol, Dept Med, Durham, NC 27710 USA.
[Povsic, Thomas J.; Rao, Sunil V.] Durham Vet Affairs Med Ctr, Durham, NC USA.
[Najjar, Samer S.] MedStar Hlth Res Inst, Washington, DC USA.
[Najjar, Samer S.; Lakatta, Edward G.] NIA, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
[Heitner, John F.] New York Methodist Hosp, Brooklyn, NY USA.
[Raman, Subha V.] Ohio State Univ, Div Cardiovasc Med, Columbus, OH 43210 USA.
[Barsness, Gregory W.] Mayo Clin, Rochester, MN USA.
RP Povsic, TJ (reprint author), Duke Univ, Med Ctr, Duke Clin Res Inst, Box 103208, Durham, NC 27710 USA.
EM thomas.povsic@duke.edu
FU National Institute on Aging, Bethesda, MD, USA [HHS-N-260-2005-00010-C];
Duke Pepper Older Americans Independence Center Research Career
Development Program in Aging Research Award, Durham, NC, USA
[5P30AG028716]
FX The authors would like to thank Peter Hoffmann for thoughtful editorial
and logistical support. The REVEAL study was supported by Intramural
Research Program contract HHS-N-260-2005-00010-C from the National
Institute on Aging, Bethesda, MD, USA. The first author was the
recipient of a Duke Pepper Older Americans Independence Center Research
Career Development Program in Aging Research Award (5P30AG028716),
Durham, NC, USA.
NR 21
TC 7
Z9 7
U1 0
U2 3
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0929-5305
EI 1573-742X
J9 J THROMB THROMBOLYS
JI J. Thromb. Thrombolysis
PD NOV
PY 2013
VL 36
IS 4
BP 375
EP 383
DI 10.1007/s11239-013-0944-6
PG 9
WC Hematology; Peripheral Vascular Disease
SC Hematology; Cardiovascular System & Cardiology
GA 249UH
UT WOS:000326802500003
PM 23700090
ER
PT J
AU Koutakis, P
Weiss, DJ
Nella, AA
Swanson, SA
Zhu, Z
Miserlis, D
Papoutsi, E
Johanning, JM
Pipinos, II
Casale, GP
AF Koutakis, Panagiotis
Weiss, Dustin J.
Nella, Aikaterini A.
Swanson, Stanley A.
Zhu, Zhen
Miserlis, Dimitrios
Papoutsi, Evlampia
Johanning, Jason M.
Pipinos, Iraklis I.
Casale, George P.
TI Myofiber Type Sensitivity of Gastrocnemius Muscle to Oxidative Stress in
Peripheral Arterial Disease Patients
SO JOURNAL OF VASCULAR SURGERY
LA English
DT Meeting Abstract
CT Annual Meeting of the Midwestern-Vascular-Surgical-Society
CY SEP 06-08, 2013
CL Chicago, IL
SP Midwestern Vasc Surg Soc
C1 Univ Nebraska Med Ctr, Dept Surg, Omaha, NE USA.
Yale Univ Med, New Haven, CT USA.
NICHHD, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0741-5214
J9 J VASC SURG
JI J. Vasc. Surg.
PD NOV
PY 2013
VL 58
IS 5
BP 1436
EP 1436
PG 1
WC Surgery; Peripheral Vascular Disease
SC Surgery; Cardiovascular System & Cardiology
GA 247DE
UT WOS:000326593900066
ER
PT J
AU Law, SHW
Sargent, TD
AF Law, Sheran H. W.
Sargent, Thomas D.
TI Maternal pak4 expression is required for primitive myelopoiesis in
zebrafish (vol 130, pg 181, 2013)
SO MECHANISMS OF DEVELOPMENT
LA English
DT Correction
C1 [Law, Sheran H. W.; Sargent, Thomas D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Dev, Sect Vertebrate Dev, Program Genom Differentiat, NIH, Bethesda, MD USA.
RP Sargent, TD (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Dev, Sect Vertebrate Dev, Program Genom Differentiat, NIH, Bethesda, MD USA.
EM sargentt@mail.nih.gov
NR 1
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0925-4773
EI 1872-6356
J9 MECH DEVELOP
JI Mech. Dev.
PD NOV-DEC
PY 2013
VL 130
IS 11-12
BP 640
EP 640
DI 10.1016/j.mod.2013.07.003
PG 1
WC Developmental Biology
SC Developmental Biology
GA 252CV
UT WOS:000326983200009
ER
PT J
AU Lee, HJ
Wu, KN
Cox, DG
Hunter, D
Hankinson, SE
Willett, WC
Sinha, R
Cho, EY
AF Lee, Hae-Jeung
Wu, Kana
Cox, David G.
Hunter, David
Hankinson, Susan E.
Willett, Walter C.
Sinha, Rashmi
Cho, Eunyoung
TI Polymorphisms in Xenobiotic Metabolizing Genes, Intakes of Heterocyclic
Amines and Red Meat, and Postmenopausal Breast Cancer
SO NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL
LA English
DT Article
ID N-ACETYLTRANSFERASE 2; AROMATIC-AMINES; COLORECTAL-CANCER;
MAMMARY-GLAND; O-ACETYLATION; RISK; EXPOSURE; NAT2; HUMANS; WOMEN
AB Heterocyclic amines (HCAs) are mutagenic compounds generated when meats are cooked at high temperature and for long duration. The findings from previous studies on the relation between HCAs and breast cancer are inconsistent, possibly because of genetic variations in the enzymes metabolizing HCAs. To evaluate whether the associations of intakes of estimated HCAs, meat-derived mutagenicity (MDM), and red meat with risk of postmenopausal breast cancer were modified by N-acetyltransferase 2 (NAT2) acetylator genotype or cytochrome P450 1A2-164 A/C (CYP1A2) polymorphism, we conducted a nested case-control study with 579 cases and 981 controls within a prospective cohort, the Nurses' Health Study. HCAs and MDM intakes were derived using a cooking method questionnaire administered in 1996. NAT2acetylator genotype, the CYP1A2 polymorphism, and intakes of HCAs, MDM, and red meat were not associated with risk of postmenopausal breast cancer. There was also no interaction between NAT2 acetylator genotype or CYP1A2 polymorphism and HCAs and MDM and red meat intake in relation to breast cancer. These results do not support the hypothesis that genetic polymorphisms of xenobiotic enzymes involved in the metabolism of HCAs may modify the associations between intakes of red meat or meat-related mutagens and breast cancer risk.
C1 [Lee, Hae-Jeung; Hunter, David; Hankinson, Susan E.; Willett, Walter C.; Cho, Eunyoung] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA.
[Lee, Hae-Jeung; Hankinson, Susan E.; Willett, Walter C.; Cho, Eunyoung] Harvard Univ, Sch Med, Boston, MA USA.
[Lee, Hae-Jeung; Wu, Kana; Hunter, David; Willett, Walter C.; Cho, Eunyoung] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Lee, Hae-Jeung] Korea Hlth Ind Dev Inst, Ctr Nutr Policy & Promot, Seoul, South Korea.
[Cox, David G.] INSERM, Canc Res Ctr Lyon, UMR1052, F-69008 Lyon, France.
[Hunter, David; Hankinson, Susan E.; Willett, Walter C.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Cambridge, MA 02138 USA.
[Sinha, Rashmi] Natl Canc Inst, NIH, Div Canc Epidemiol & Genet, Rockville, MD USA.
RP Cho, EY (reprint author), Channing Labs, 181 Longwood Ave, Boston, MA 02115 USA.
EM eunyoung.cho@channing.harvard.edu
RI Sinha, Rashmi/G-7446-2015; Cox, David/A-2023-2009
OI Sinha, Rashmi/0000-0002-2466-7462; Cox, David/0000-0002-2152-9259
FU American Institute for Cancer Research; National Cancer Institute,
National Institutes of Health [CA 87969]
FX This work was supported by a grant from the American Institute for
Cancer Research as well as grant CA 87969 from the National Cancer
Institute, National Institutes of Health. We are indebted to Rong Tilney
for computer support. In addition, we thank the participants and staff
of the Nurses' Health Study, for their valuable contributions as well as
the following state cancer registries for their help: AL, AZ, AR, CA,
CO, CT, DE, FL, GA, ID, IL, IN, IA, KY, LA, ME, MD, MA, MI, NE, NH, NJ,
NY, NC, ND, OH, OK, OR, PA, RI, SC, TN, TX, VA, WA, and WY.
NR 56
TC 6
Z9 6
U1 0
U2 4
PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD
PI ABINGDON
PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND
SN 0163-5581
EI 1532-7914
J9 NUTR CANCER
JI Nutr. Cancer
PD NOV 1
PY 2013
VL 65
IS 8
BP 1122
EP 1131
DI 10.1080/01635581.2013.824991
PG 10
WC Oncology; Nutrition & Dietetics
SC Oncology; Nutrition & Dietetics
GA 251HL
UT WOS:000326918300003
PM 24099317
ER
PT J
AU Galgani, JE
Kelley, DE
Albu, JB
Krakoff, J
Smith, SR
Bray, GA
Ravussin, E
AF Galgani, Jose E.
Kelley, David E.
Albu, Jeanine B.
Krakoff, Jonathan
Smith, Steven R.
Bray, George A.
Ravussin, Eric
CA Look AHEAD Adipose Res Grp
TI Adipose Tissue Expression of Adipose (WDTC1) Gene Is Associated with
Lower Fat Mass and Enhanced Insulin Sensitivity in Humans
SO OBESITY
LA English
DT Article
ID OBESITY
AB Objective: The overexpression of the adipose gene (adp/WDTC1) in mice inhibits lipid accumulation and improves the metabolic profile. Subcutaneous fat adp expression in humans and its relation to metabolic parameters was evaluated.
Design and Methods: Abdominal subcutaneous fat adp expression, insulin sensitivity (clamp), and respiratory quotient (RQ; indirect calorimetry) were assessed in: 36 obese and 56 BMI-, race-, and sex-matched type 2 diabetic volunteers (Look AHEAD Adipose Ancillary Study); 37 nondiabetic Pima Indians including obese (n=18) and nonobese (n=19) subjects and; 62 nonobese nondiabetic subjects at the Pennington Center in the ADAPT study.
Results: In the Look AHEAD Study, adp expression normalized for cyclophilin B was higher in males versus females (1.27 +/- 0.06 vs. 1.11 +/- 0.04; P < 0.01) but not after controlling for body fat. Adp expression was not influenced by the presence of diabetes but was related to body fat (r = -0.23; P = 0.03), insulin sensitivity (r = 0.23; P = 0.03) and fasting/insulin-stimulated RQ (r = 0.31 and 0.33; P < 0.01). In Pima Indians, adp expression was also higher in males versus females (1.00 +/- 0.05 vs. 0.77 +/- 0.05; P = 0.02) and higher in nonobese versus obese (1.02 +/- 0.05 vs. 0.80 +/- 0.06; P = 0.03). In the ADAPT study, there was no difference in adp expression between males and females.
Conclusion: Consistent with animal studies, our results suggest that high adp expression in human adipose tissue is associated with lower adiposity and enhanced glucose utilization.
C1 [Galgani, Jose E.; Bray, George A.; Ravussin, Eric] Pennington Biomed Res Ctr, Baton Rouge, LA 70808 USA.
[Galgani, Jose E.] Pontificia Univ Catolica Chile, Dept Nutr Diabet & Metab, Sch Med, Santiago, Chile.
[Kelley, David E.] Univ Pittsburgh, Dept Med, Pittsburgh, PA USA.
[Albu, Jeanine B.] St Lukes Roosevelt Hosp, New York Obes Nutr Res Ctr, New York, NY 10025 USA.
[Krakoff, Jonathan] NIDDK, Obes & Diabet Clin Res Section, NIH, Phoenix, AZ USA.
[Smith, Steven R.] Sanford Burnham Med Res Inst, Diabet Obes Res Ctr, Sanford, FL USA.
RP Ravussin, E (reprint author), Pennington Biomed Res Ctr, 6400 Perkins Rd, Baton Rouge, LA 70808 USA.
EM eric.ravussin@pbrc.edu
FU USDA [2010-34323-21052]; University of Pittsburgh Obesity & Nutrition
Research Center [P30-DK46204]; University of Pittsburgh General Clinical
Research Center [MO1-RR000056]; Pennington Biomedical Research Center
Nutrition Obesity Research Center [P30-DK072476]; Columbia University
Diabetes and Endocrinology Research Center [P30-DK63608]; New York
Obesity Research Center [P30-DK26687]; Columbia University Clinical
Translational Service Award (CTSA) [UL1 RR024156]; International
Nutrition Foundation/Ellison Medical Foundation; [DK60412]; [U01
DK056990]
FX This study was funded by DK60412 (ER), U01 DK056990 (DEK), USDA
2010-34323-21052 (GAB), University of Pittsburgh Obesity & Nutrition
Research Center (P30-DK46204), the University of Pittsburgh General
Clinical Research Center (MO1-RR000056), Pennington Biomedical Research
Center Nutrition Obesity Research Center (P30-DK072476), the Columbia
University Diabetes and Endocrinology Research Center (P30-DK63608), the
New York Obesity Research Center (P30-DK26687) and the Columbia
University Clinical Translational Service Award (CTSA, UL1 RR024156).
JEG was supported by a fellowship from The International Nutrition
Foundation/Ellison Medical Foundation.
NR 12
TC 2
Z9 3
U1 0
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1930-7381
EI 1930-739X
J9 OBESITY
JI Obesity
PD NOV
PY 2013
VL 21
IS 11
BP 2244
EP 2248
DI 10.1002/oby.20371
PG 5
WC Endocrinology & Metabolism; Nutrition & Dietetics
SC Endocrinology & Metabolism; Nutrition & Dietetics
GA 247RO
UT WOS:000326637400013
PM 23512946
ER
PT J
AU Mitchell, S
Castro, K
St Germain, D
Denicoff, A
Watkins-Bruner, D
O'Mara, A
AF Mitchell, Sandra
Castro, Kathleen
St Germain, Diane
Denicoff, Andrea
Watkins-Bruner, Deborah
O'Mara, Ann
TI CAPTURING SYMPTOM BURDEN AND TREATMENT TOLERABILITY IN CANCER CLINICAL
TRIALS: NCI'S PATIENT-REPORTED OUTCOMES VERSION OF THE COMMON
TERMINOLOGY CRITERIA FOR ADVERSE EVENTS (PRO-CTCAE)
SO ONCOLOGY NURSING FORUM
LA English
DT Meeting Abstract
C1 [Mitchell, Sandra; Castro, Kathleen; St Germain, Diane; Denicoff, Andrea; O'Mara, Ann] NCI, Rockville, MD USA.
[Watkins-Bruner, Deborah] Emory Univ, Nell Hodgson Woodruff Sch Nursing, Atlanta, GA 30322 USA.
NR 0
TC 0
Z9 0
U1 1
U2 4
PU ONCOLOGY NURSING SOC
PI PITTSBURGH
PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA
SN 0190-535X
J9 ONCOL NURS FORUM
JI Oncol. Nurs. Forum
PD NOV
PY 2013
VL 40
IS 6
SU S
BP E454
EP E454
PG 1
WC Oncology; Nursing
SC Oncology; Nursing
GA 250IV
UT WOS:000326847400106
ER
PT J
AU Elder, AM
Henderson, DM
Nalls, AV
Wilham, JM
Caughey, BW
Hoover, EA
Kincaid, AE
Bartz, JC
Mathiason, CK
AF Elder, Alan M.
Henderson, Davin M.
Nalls, Amy V.
Wilham, Jason M.
Caughey, Byron W.
Hoover, Edward A.
Kincaid, Anthony E.
Bartz, Jason C.
Mathiason, Candace K.
TI In Vitro Detection of prionemia in TSE-Infected Cervids and Hamsters
SO PLOS ONE
LA English
DT Article
ID CREUTZFELDT-JAKOB-DISEASE; CHRONIC WASTING DISEASE; SCRAPIE
VIRUS-INFECTION; BLOOD-TRANSFUSION; CYCLIC AMPLIFICATION; SEEDED
CONVERSION; PROTEIN; TRANSMISSION; SHEEP; DEER
AB Blood-borne transmission of infectious prions during the symptomatic and asymptomatic stages of disease occurs for both human and animal transmissible spongiform encephalopathies (TSEs). The geographical distribution of the cervid TSE, chronic wasting disease (CWD), continues to spread across North America and the prospective number of individuals harboring an asymptomatic infection of human variant Creutzfeldt-Jakob Disease (vCJD) in the United Kingdom has been projected to be similar to 1 in 3000 residents. Thus, it is important to monitor cervid and human blood products to ensure herd health and human safety. Current methods for detecting blood-associated prions rely primarily upon bioassay in laboratory animals. While bioassay provides high sensitivity and specificity, it requires many months, animals, and it is costly. Here we report modification of the real time quaking-induced conversion (RT-QuIC) assay to detect blood-borne prions in whole blood from prion-infected preclinical white-tailed deer, muntjac deer, and Syrian hamsters, attaining sensitivity of > 90% while maintaining 100% specificity. Our results indicate that RT-QuIC methodology as modified can provide consistent and reliable detection of blood-borne prions in preclinical and symptomatic stages of two animal TSEs, offering promise for prionemia detection in other species, including humans.
C1 [Elder, Alan M.; Henderson, Davin M.; Nalls, Amy V.; Hoover, Edward A.; Mathiason, Candace K.] Colorado State Univ, Dept Microbiol Immunol & Pathol, Ft Collins, CO 80523 USA.
[Wilham, Jason M.; Caughey, Byron W.] NIAID, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA.
[Kincaid, Anthony E.; Bartz, Jason C.] Creighton Univ, Omaha, NE 68178 USA.
RP Mathiason, CK (reprint author), Colorado State Univ, Dept Microbiol Immunol & Pathol, Ft Collins, CO 80523 USA.
EM candace.mathiason@colostate.edu
RI Mathiason, Candace/E-7843-2017;
OI Mathiason, Candace/0000-0002-5920-4556; Bartz, Jason/0000-0003-4081-7886
FU Morris Animal Foundation [D12ZO-045]; [NIH-RO1 093634-01]; [NIH-R01
N5061902]; [NIAID-NO1-AI-25491]; [RO1 NS061994]; [RO1 NS061994-03S1]
FX The work at Colorado State University was supported by NIH-RO1
093634-01, NIH-R01 N5061902, NIAID-NO1-AI-25491 and Morris Animal
Foundation D12ZO-045. Work done at Creighton University was supported by
RO1 NS061994 and RO1 NS061994-03S1. The funders had no role in study
design, data collection and analysis, decision to publish, or
preparation of the manuscript.
NR 60
TC 28
Z9 28
U1 0
U2 11
PU PUBLIC LIBRARY SCIENCE
PI SAN FRANCISCO
PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA
SN 1932-6203
J9 PLOS ONE
JI PLoS One
PD NOV 1
PY 2013
VL 8
IS 11
AR e80203
DI 10.1371/journal.pone.0080203
PG 15
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 245XZ
UT WOS:000326499300097
PM 24224043
ER
PT J
AU Weng, MT
Luo, J
AF Weng, Meng-Tzu
Luo, Ji
TI The enigmatic ERH protein: its role in cell cycle, RNA splicing and
cancer
SO PROTEIN & CELL
LA English
DT Review
DE enhancer of rudimentary homolog; mRNA splicing; mitosis; CENP-E; KRAS;
colorectal cancer
ID RUDIMENTARY HOMOLOG ERH; ZINC-FINGER PROTEIN; TRANSCRIPTIONAL REPRESSOR;
DROSOPHILA-MELANOGASTER; MOLECULAR PARTNER; CRYSTAL-STRUCTURE; HUMAN
ENHANCER; RAS ONCOGENE; GENE; CHROMOSOME
AB Enhancer of rudimentary homolog (ERH) is a small, highly conserved protein among eukaryotes. Since its discovery nearly 20 years ago, its molecular function has remained enigmatic. It has been implicated to play a role in transcriptional regulation and in cell cycle. We recently showed that ERH binds to the Sm complex and is required for the mRNA splicing of the mitotic motor protein CENP-E. Furthermore, cancer cells driven by mutations in the KRAS oncogene are particularly sensitive to RNAi-mediated suppression of ERH function, and ERH expression is inversely correlated with survival in colorectal cancer patients whose tumors harbor KRAS mutation. These recent findings indicate that ERH plays an important role in cell cycle through its mRNA splicing activity and is critically required for genomic stability and cancer cell survival.
C1 [Weng, Meng-Tzu; Luo, Ji] NCI, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Luo, J (reprint author), NCI, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
EM ji.luo@nih.gov
FU Liver Disease Prevention and Treatment Research Foundation of Taiwan;
U.S. National Cancer Institute
FX This work is supported by the Liver Disease Prevention and Treatment
Research Foundation of Taiwan to M.Z.W. and by the Intramural Program of
the U.S. National Cancer Institute to J.L.
NR 35
TC 6
Z9 6
U1 0
U2 5
PU HIGHER EDUCATION PRESS
PI BEIJING
PA SHATANHOU ST 55, BEIJING 100009, PEOPLES R CHINA
SN 1674-800X
EI 1674-8018
J9 PROTEIN CELL
JI Protein Cell
PD NOV
PY 2013
VL 4
IS 11
BP 807
EP 812
DI 10.1007/s13238-013-3056-3
PG 6
WC Cell Biology
SC Cell Biology
GA 251OQ
UT WOS:000326939900002
PM 24078386
ER
PT J
AU Geras-Raaka, E
Neumann, S
Gershengorn, MC
AF Geras-Raaka, Elizabeth
Neumann, Susanne
Gershengorn, Marvin C.
TI Persistent cAMP Signaling by TSH Receptors Revealed by Phosphodiesterase
Inhibition
SO THYROID
LA English
DT Article
ID THYROTROPIN RECEPTOR; HORMONE-RECEPTOR; AGONIST
AB Background: It is controversial whether persistent signaling by the thyrotropin (TSH) receptor (TSHR) is cell-type specific. We reported persistent TSHR signaling in human embryonic kidney 293 (HEK293) cells expressing human TSHRs (HEK-TSHRs), whereas another group reported persistent signaling in mouse thyroid follicles but not in HEK293 cells. Herein, we test this hypothesis directly. Methods: We used two methods to measure persistent signaling in HEK-TSHRs and confirm our previous observations. In Method 1, we used a chemiluminescent immunoassay to measure intracellular cAMP accumulation over 30-60min by adding a phosphodiesterase inhibitor to the incubation medium. In Method 2, we used an intracellular biosensor to record cAMP levels continuously. Results: Using Method 1, we show that TSHR signals persistently in human thyrocytes and human osteosarcoma U2OS-TSHR cells. Using Method 1 in HEK-TSHRs, we show that after 5min, the phosphodiesterase inhibitor isobutylmethylxanthine (IBMX) increases cAMP to 2.5 pmol/well, TSH increases cAMP to 1.6 pmol/well, but IBMX added 30min after TSH withdrawal increases cAMP to 105 pmol/well. Using Method 2 in HEK-TSHRs, we confirm that without IBMX, TSH causes a transient increase in cAMP and 30min after TSH withdrawal, IBMX increases cAMP in cells pretreated with TSH more rapidly and to a higher level than IBMX added to cells not pre-exposed to TSH. Lastly, using Method 2, we show that in HEK-TSHRs phosphodiesterases types 3 and 4 are involved in degrading cAMP as the specific inhibitors Rolipram and Milrinone expose persistent TSHR signaling. Conclusions: We conclude that persistent TSHR activation occurs in human thyrocytes, U2OS-TSHR cells and HEK-TSHRs; it is not cell-type specific but is revealed by inhibiting phosphodiesterases.
C1 [Geras-Raaka, Elizabeth; Neumann, Susanne; Gershengorn, Marvin C.] NIDDK, Lab Endocrinol & Receptor Biol, NIH, Bethesda, MD 20892 USA.
RP Gershengorn, MC (reprint author), NIDDK, LERB, NIH, 50 South Dr, Bethesda, MD 20892 USA.
EM marving@intra.niddk.nih.gov
FU Intramural Research Program of the NIH [1 Z01 DK011006]
FX This research was supported by the Intramural Research Program of the
NIH (1 Z01 DK011006). We thank Bernice Samuels for her excellent
technical assistance and Alisa Boutin for generating U2OS-TSHR cells.
NR 13
TC 2
Z9 2
U1 0
U2 1
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1050-7256
EI 1557-9077
J9 THYROID
JI Thyroid
PD NOV 1
PY 2013
VL 23
IS 11
BP 1484
EP 1489
DI 10.1089/thy.2013.0089
PG 6
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 246YV
UT WOS:000326578800019
PM 23713896
ER
PT J
AU Flegel, WA
Chiosea, I
Sachs, UJ
Bein, G
AF Flegel, Willy A.
Chiosea, Ion
Sachs, Ulrich J.
Bein, Gregor
TI External quality assessment in molecular immunohematology: the INSTAND
proficiency test program
SO TRANSFUSION
LA English
DT Editorial Material
ID INTERNATIONAL WORKSHOP; ALLOIMMUNE THROMBOCYTOPENIA; NEUTROPHIL
ALLOANTIGENS; SEROLOGY WORKSHOP; HUMAN PLATELET; BLOOD; TRANSFUSION;
DNA; ANTIGENS; SOCIETY
AB BackgroundGenotyping for red blood cell (RBC), platelet (PLT), and granulocyte antigens is a new tool for clinical pathology, transfusion medicine services, and blood banks. Proficiency in laboratory tests can be established by external quality assessments (EQAs), which are required for clinical application in many health care systems. There are few EQAs for molecular immunohematology.
Study Design and MethodsWe analyzed the participation and pass rates in an EQA for RBC, PLT, and granulocyte antigens. This EQA was distributed by INSTAND, a large nonprofit provider of proficiency tests, twice per year since Fall 2006 as EQA Number 235 Immunohematology A (molecular diagnostic). The coordinators defined at the outset which alleles are mandatory for detection.
ResultsThe number of participants steadily increased from 51 to 73 per proficiency by Fall 2012. More than 60 institutions utilized this EQA at least once a year. Approximately 80% of them participated in RBC, 68% in PLT, and 22% in granulocyte systems. With the exceptions of RHD (82%) and granulocytes (85%), pass rates exceeded 93%. While the pass rate increased for granulocyte and decreased for the ABO system, the pass rates for the other systems changed little over 61/2 years.
ConclusionsThe INSTAND proficiency test program was regularly used for EQA by many institutions, particularly in Central Europe. While the technical standards and pass rates in the participating laboratories were high, there has been little improvement in pass rates since 2006.
C1 [Flegel, Willy A.; Chiosea, Ion] NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA.
[Sachs, Ulrich J.; Bein, Gregor] Univ Giessen, Inst Clin Immunol & Transfus Med, Giessen, Germany.
RP Flegel, WA (reprint author), NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA.
EM bill.flegel@nih.gov
FU Intramural NIH HHS [Z99 CL999999]
NR 55
TC 3
Z9 3
U1 0
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0041-1132
EI 1537-2995
J9 TRANSFUSION
JI Transfusion
PD NOV
PY 2013
VL 53
IS 11
SI SI
BP 2850
EP 2858
DI 10.1111/trf.12414
PN PT2
PG 9
WC Hematology
SC Hematology
GA 249HP
UT WOS:000326768600007
PM 24111785
ER
PT J
AU Velliquette, RW
Hue-Roye, K
Lomas-Francis, C
Gillen, B
Schierts, J
Gentzkow, K
Peyrard, T
von Zabern, I
Flegel, WA
Rodberg, K
Debnath, AK
Lee, S
Reid, ME
AF Velliquette, Randall W.
Hue-Roye, Kim
Lomas-Francis, Christine
Gillen, Barbara
Schierts, Jennifer
Gentzkow, Kristie
Peyrard, Thierry
von Zabern, Inge
Flegel, Willy A.
Rodberg, Karen
Debnath, Asim K.
Lee, Soohee
Reid, Marion E.
TI Molecular basis of two novel and related high-prevalence antigens in the
Kell blood group system, KUCI and KANT, and their serologic and spatial
association with K11 and KETI
SO TRANSFUSION
LA English
DT Article
ID INTERNATIONAL SOCIETY; POINT MUTATIONS; GROUP PROTEIN; PHENOTYPE;
EXPRESSION; GLYCOPROTEIN; TERMINOLOGY; VARIANT; SERINE; ALLELE
AB BackgroundThe numerous antigens in the Kell blood group system result from missense nucleotide changes in KEL. Antibodies to antigens in this system can be clinically important. We describe six probands whose plasma contained antibodies to high-prevalence Kell antigens and discuss their relationship.
Study Design and MethodsPolymerase chain reaction amplification, direct sequencing, restriction fragment length polymorphism assays, hemagglutination, flow cytometry, and protein modeling were performed by standard methods.
ResultsProband 1 (KUCI) and her serologically compatible sister were heterozygous for a nucleotide change in Exon 11 (KEL*1271C/T; Ala424Val). Proband 2 (KANT) was heterozygous for KEL*1283G/T (Arg428Leu) and KEL*1216C/T (Arg406Stop) in Exon 11. Red blood cells (RBCs) from Proband 1 and her sister were not agglutinated by plasma from Proband 2; however, RBCs from Proband 2 were agglutinated by plasma from Proband 1. Probands 3, 4, 5, and 6 had the KEL*1391C>T change associated with the previously reported KETI- phenotype. Proband 5 was also homozygous for KEL*905T>C encoding the K11-K17+ phenotype. Hemagglutination studies revealed an association between KUCI, KANT, KETI, and K11. Protein modeling indicated that whereas Ala424 and Arg428 are clustered, Val302 and Thr464 are not.
ConclusionAla424 in the Kell glycoprotein is associated with the high-prevalence Kell antigen, KUCI (ISBT 006032), which is detected by the antibody of Proband 1. Arg428 is associated with the high-prevalence Kell antigen, KANT (ISBT 006033). The association between KUCI, KANT, KETI, and K11 and the results of protein modeling are discussed.
C1 New York Blood Ctr, Lab Immunohematol & Genom, Long Isl City, NY USA.
New York Blood Ctr, Lab Immunochem, Lab Mol Modeling & Drug Design, New York, NY 10065 USA.
New York Blood Ctr, Lab Membrane Biochem, New York, NY 10065 USA.
Mem Blood Ctr, St Paul, MN USA.
Medctr One, Bismarck, ND USA.
Natl Inst Blood Transfus, Natl Reference Ctr Blood Grp, Paris, France.
Univ Hosp Ulm, Dept Transfus Med, Inst Clin Transfus Med & Immunogenet, Ulm, Germany.
Baden Wurttemberg Hessen, Inst Ulm, German Red Cross Blood Donor Serv, Ulm, Germany.
NIH, Lab Serv Sect, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA.
Amer Red Cross, Pomona, CA USA.
RP Reid, ME (reprint author), New York Blood Ctr, Lab Immunochem, 310 East 67 St, New York, NY 10065 USA.
EM mreid@nybloodcenter.org
FU NIH [R01 HL075716]
FX This study was funded in part by NIH grant R01 HL075716 (SL).
NR 43
TC 5
Z9 5
U1 1
U2 2
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 2013
VL 53
IS 11
SI SI
BP 2872
EP 2881
DI 10.1111/trf.12200
PN PT2
PG 10
WC Hematology
SC Hematology
GA 249HP
UT WOS:000326768600010
PM 23560718
ER
PT J
AU Orzinska, A
Guz, K
Polin, H
Pelc-Klopotowska, M
Bednarz, J
Gielezynska, A
Sliwa, B
Kowalewska, M
Pawlowska, E
Wlodarczyk, B
Malaga, M
Zmudzin, A
Krzemienowska, M
Srivastava, K
Michalewska, B
Gabriel, C
Flegel, WA
Brojer, E
AF Orzinska, Agnieszka
Guz, Katarzyna
Polin, Helene
Pelc-Klopotowska, Monika
Bednarz, Justyna
Gielezynska, Agata
Sliwa, Beata
Kowalewska, Malgorzata
Pawlowska, Elzbieta
Wlodarczyk, Boguslawa
Malaga, Malgorzata
Zmudzin, Alicja
Krzemienowska, Magdalena
Srivastava, Kshitij
Michalewska, Bogumila
Gabriel, Christian
Flegel, Willy A.
Brojer, Ewa
TI RHD variants in Polish blood donors routinely typed as D-
SO TRANSFUSION
LA English
DT Article
ID ANTI-D IMMUNIZATION; WEAK-D PHENOTYPES; MOLECULAR-BASIS; D
ALLOIMMUNIZATION; CELL UNITS; D-EL; ALLELES; GENE; IDENTIFICATION;
GERMANY
AB BackgroundBlood donors exhibiting a weak D or DEL phenotypical expression may be mistyped D- by standard serology hence permitting incompatible transfusion to D- recipients. Molecular methods may overcome these technical limits. Our aim was to estimate the frequency of RHD alleles among the apparently D- Polish donor population and to characterize its molecular background.
Study Design and MethodsPlasma pools collected from 31,200 consecutive Polish donors typed as D- were tested by real-time polymerase chain reaction (PCR) for the presence of RHD-specific markers located in Intron 4 and Exons 7 and 10. RHD+ individuals were characterized by PCR or cDNA sequencing and serology.
ResultsPlasma cross-pool strategy revealed 63 RHD+ donors harboring RHD*01N.03 (n=17), RHD*15 (n=12), RHD*11 (n=7), RHD*DEL8 (n=3), RHD*01W.2 (n=3), RHD-CE(10) (n=3), RHD*01W.3, RHD*01W.9, RHD*01N.05, RHD*01N.07, RHD*01N.23, and RHD(IVS1-29G>C) and two novel alleles, RHD*(767C>G) (n=3) and RHD*(1029C>A). Among 47 cases available for serology, 27 were shown to express the D antigen
Conclusion1) Plasma cross-pool strategy is a reliable and cost-effective tool for RHD screening. 2) Only 0.2% of D- Polish donors carry some fragments of the RHD gene; all of them were C or E+. 3) Almost 60% of the detected RHD alleles may be potentially immunogenic when transfused to a D- recipient.
C1 Inst Hematol & Blood Transfus, Dept Immunohematol & Immunol Transfus Med, PL-00957 Warsaw, Poland.
Reg Blood Transfus Ctr, Warsaw, Poland.
Reg Blood Transfus Ctr, Krakow, Poland.
Reg Blood Transfus Ctr, Gdansk, Poland.
Reg Blood Transfus Ctr, Raciborz, Poland.
Reg Blood Transfus Ctr, Kalisz, Poland.
Reg Blood Transfus Ctr, Kielce, Poland.
Reg Blood Transfus Ctr, Radom, Poland.
Red Cross Transfus Ctr Upper Austria, Linz, Austria.
NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA.
RP Orzinska, A (reprint author), Inst Hematol & Blood Transfus, 5th Chocimska St, PL-00957 Warsaw, Poland.
EM aorzinska@ihit.waw.pl; kguz@ihit.waw.pl
RI Gabriel, Christian/A-1689-2014
OI Gabriel, Christian/0000-0003-2043-9320
FU Polish Committee for Scientific Research [N N404 188036]
FX This study was supported by Grant N N404 188036 from the Polish
Committee for Scientific Research.
NR 39
TC 6
Z9 6
U1 0
U2 7
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 2013
VL 53
IS 11
SI SI
BP 2945
EP 2953
DI 10.1111/trf.12230
PN PT2
PG 9
WC Hematology
SC Hematology
GA 249HP
UT WOS:000326768600019
PM 23634715
ER
PT J
AU von Zabern, I
Wagner, FF
Moulds, JM
Moulds, JJ
Flegel, WA
AF von Zabern, Inge
Wagner, Franz F.
Moulds, Joann M.
Moulds, John J.
Flegel, Willy A.
TI D category IV: a group of clinically relevant and phylogenetically
diverse partial D
SO TRANSFUSION
LA English
DT Article
ID BLOOD-GROUP SYSTEM; RH ANTIGEN-D; WEAK-D-TYPES; MOLECULAR-BASIS;
D-EPITOPES; COORDINATORS REPORT; D PHENOTYPES; AMINO-ACIDS; ALLELES;
EXPRESSION
AB BackgroundThe D typing strategies in several European countries protect carriers of D category VI (DVI) from anti-D immunization but not carriers of other partial D. Besides DVI, one of the clinically most important partial D is D category IV (DIV). A detailed description and direct comparison of the different DIV types was missing.
Study Design and MethodsRHD nucleotide sequences were determined from genomic DNA. D epitope patterns were established with commercial monoclonal anti-D panels.
ResultsDIV comprises several variants of the D antigen with distinct serology, molecular structures, evolutionary origins, and ethnic prevalences. The DIV phenotype is determined by 350H shared by all, but not limited to, DIV variants which are further divided into DIVa and DIVb. The DIVa phenotype is expressed by DIV Type 1.0 harboring 350H and the dispersed amino acids 62F, 137V, and 152T. The DIVb phenotype is expressed by DIV Type 3 to Type 5 representing RHD-CE-D hybrids. Four of the six postulated DIV variants were encountered among 23 DIV samples analyzed. Of 12 DIV carriers with anti-D, 10 were female and seven likely immunized by pregnancy. Two DIV-related alleles are newly described: DWN, which differs from DIV Type 4 by 350D and epitope pattern. DNT carries 152T, known to cause a large D antigen density.
ConclusionDIV alleles arose from at least two independent evolutionary events. DIV Type 1.0 with DIVa phenotype belongs to the oldest extant human RHD alleles. DIV Type 2 to Type 5 with DIVb phenotype arose from more recent gene conversions. Anti-D immunization, especially dreaded in pregnancies, will be avoided not only in carriers of DVI but also in carriers of other D variants like DIV, if our proposed D typing strategy is adopted.
C1 Univ Hosp, Dept Transfus Med, Ulm, Germany.
Inst Clin Transfus Med & Immunogenet, Ulm, Germany.
Inst Ulm, DRK German Red Cross Blood Donor Serv Baden Wurtt, Ulm, Germany.
Inst Springe, DRK Blood Donor Serv NSTOB, Springe, Germany.
LifeShare Blood Ctrs, Sci Support Serv, Shreveport, LA USA.
[Flegel, Willy A.] NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA.
RP Flegel, WA (reprint author), NIH, Dept Transfus Med, Ctr Clin, Bldg 10,Room 1C733C,10 Ctr Dr, Bethesda, MD 20892 USA.
EM bill.flegel@nih.gov
FU Intramural Research Programs of the DRK-Blutspendedienst
Baden-Wurttemberg-Hessen, Mannheim; NIH Clinical Center
FX This work was supported by the Intramural Research Programs of the
DRK-Blutspendedienst Baden-Wurttemberg-Hessen, Mannheim, and the NIH
Clinical Center.
NR 74
TC 5
Z9 5
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 2013
VL 53
IS 11
SI SI
BP 2960
EP 2973
DI 10.1111/trf.12145
PN PT2
PG 14
WC Hematology
SC Hematology
GA 249HP
UT WOS:000326768600021
PM 23461862
ER
PT J
AU Magill, SS
Klompas, M
Balk, R
Burns, SM
Deutschman, CS
Diekema, D
Fridkin, S
Greene, L
Guh, A
Gutterman, D
Hammer, B
Henderson, D
Hess, DR
Hill, NS
Horan, T
Kollef, M
Levy, M
Septimus, E
VanAntwerpen, C
Wright, D
Lipsett, P
AF Magill, Shelley S.
Klompas, Michael
Balk, Robert
Burns, Suzanne M.
Deutschman, Clifford S.
Diekema, Daniel
Fridkin, Scott
Greene, Linda
Guh, Alice
Gutterman, David
Hammer, Beth
Henderson, David
Hess, Dean R.
Hill, Nicholas S.
Horan, Teresa
Kollef, Marin
Levy, Mitchell
Septimus, Edward
VanAntwerpen, Carole
Wright, Don
Lipsett, Pamela
TI Developing a new national approach to surveillance for
ventilator-associated events: Executive summary
SO AMERICAN JOURNAL OF INFECTION CONTROL
LA English
DT Article
DE Ventilator-associated pneumonia; Intensive care unit; Epidemiology;
Public health; Critical care; Mechanical ventilation
AB In September 2011, the Centers for Disease Control and Prevention (CDC) convened a Ventilator-Associated Pneumonia (VAP) Surveillance Definition Working Group to organize a formal process for leaders and experts of key stakeholder organizations to discuss the challenges of VAP surveillance definitions and to propose new approaches to VAP surveillance in adult patients (Table 1). The charges to the Working Group were to (1) critically review a draft, streamlined VAP surveillance definition developed for use in adult patients; (2) suggest modifications to enhance the reliability and credibility of the surveillance definition within the critical care and infection prevention communities; and (3) propose a final adult surveillance definition algorithm to be implemented in the CDC's National Healthcare Safety Network (NHSN), taking into consideration the potential future use of the definition algorithm in public reporting, interfacility comparisons, and pay-for-reporting and pay-for-performance programs. Published by Elsevier Inc. on behalf of the Association for Professionals in Infection Control and Epidemiology, Inc.
C1 [Magill, Shelley S.; Fridkin, Scott; Guh, Alice; Horan, Teresa] Ctr Dis Control & Prevent, Div Healthcare Qual Promot, Atlanta, GA 30329 USA.
[Klompas, Michael] Harvard Univ, Sch Med, Dept Populat Med, Boston, MA USA.
[Klompas, Michael] Harvard Pilgrim Hlth Care Inst, Boston, MA USA.
[Klompas, Michael] Brigham & Womens Hosp, Infect Control Dept, Boston, MA 02115 USA.
[Klompas, Michael] Soc Healthcare Epidemiol Amer, Arlington, VA USA.
[Balk, Robert] Rush Univ, Sch Med, Div Pulm & Crit Care Med, Chicago, IL 60612 USA.
[Burns, Suzanne M.] Univ Virginia, Sch Nursing Crit & Acute Care, Charlottesville, VA USA.
[Deutschman, Clifford S.] Univ Penn, Perelman Sch Med, Dept Anesthesiol & Crit Care, Philadelphia, PA 19104 USA.
[Diekema, Daniel] Univ Iowa, Div Infect Dis, Carver Coll Med, Iowa City, IA USA.
[Diekema, Daniel] Healthcare Infect Control Practices Advisory Comm, Surveillance Working Grp, Atlanta, GA USA.
[Greene, Linda] Rochester Gen Hlth Syst, Infect Prevent & Control Dept, Rochester, NY USA.
[Greene, Linda] Assoc Profess Infect Control & Epidemiol, Washington, DC USA.
[Gutterman, David] Med Coll Wisconsin, Dept Med, Milwaukee, WI 53226 USA.
[Hammer, Beth] Zablocki VA Med Ctr, Dept Cardiol, Milwaukee, WI USA.
[Henderson, David] NIH, Ctr Clin, Bethesda, MD 20892 USA.
[Hess, Dean R.] Massachusetts Gen Hosp, Dept Resp Care, Boston, MA 02114 USA.
[Hess, Dean R.] Harvard Univ, Sch Med, Dept Anaesthesia, Boston, MA 02115 USA.
[Hess, Dean R.] Amer Assoc Resp Care, Irving, TX USA.
[Hill, Nicholas S.] Tufts Med Ctr, Div Pulm & Crit Care Med, Boston, MA USA.
[Kollef, Marin] Washington Univ, Div Pulm & Crit Care Med, St Louis, MO USA.
[Levy, Mitchell] Brown Univ, Rhode Isl Hosp, Warren Alpert Med Sch, Div Pulm Crit Care & Sleep, Providence, RI 02903 USA.
[Septimus, Edward] Texas A&M Hlth Sci Ctr, Dept Internal Med, College Stn, TX USA.
[Septimus, Edward] Infect Dis Soc Amer, Arlington, VA USA.
[VanAntwerpen, Carole] New York State Dept Hlth, Bur Healthcare Associated Infect, Albany, NY USA.
[VanAntwerpen, Carole] Council State & Territorial Epidemiologists, Atlanta, GA USA.
[Wright, Don] US Dept HHS, Off Dis Prevent & Hlth Promot, Washington, DC 20201 USA.
[Lipsett, Pamela] Johns Hopkins Univ, Sch Med, Dept Surg Anesthesiol & Crit Care Med, Baltimore, MD USA.
RP Magill, SS (reprint author), Ctr Dis Control & Prevent, Div Healthcare Qual Promot, 1600 Clifton Rd,MS A-24, Atlanta, GA 30329 USA.
EM smagill@cdc.gov
OI Diekema, Daniel/0000-0003-1273-0724
FU Centers for Disease Control and Prevention (CDC)
FX Supported by the Centers for Disease Control and Prevention (CDC).
NR 2
TC 3
Z9 4
U1 1
U2 3
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0196-6553
EI 1527-3296
J9 AM J INFECT CONTROL
JI Am. J. Infect. Control
PD NOV
PY 2013
VL 41
IS 11
BP 1096
EP 1099
DI 10.1016/j.ajic.2013.07.001
PG 4
WC Public, Environmental & Occupational Health; Infectious Diseases
SC Public, Environmental & Occupational Health; Infectious Diseases
GA 242KY
UT WOS:000326241700031
PM 24176770
ER
PT J
AU Bailit, JL
Grobman, WA
Rice, MM
Spong, CY
Wapner, RJ
Varner, MW
Thorp, JM
Leveno, KJ
Caritis, SN
Shubert, PJ
Tita, AT
Saade, G
Sorokin, Y
Rouse, DJ
Blackwell, SC
Tolosa, JE
Van Dorsten, JP
AF Bailit, Jennifer L.
Grobman, William A.
Rice, Madeline Murguia
Spong, Catherine Y.
Wapner, Ronald J.
Varner, Michael W.
Thorp, John M.
Leveno, Kenneth J.
Caritis, Steve N.
Shubert, Phillip J.
Tita, Alan T.
Saade, George
Sorokin, Yoram
Rouse, Dwight J.
Blackwell, Sean C.
Tolosa, Jorge E.
Van Dorsten, J. Peter
CA Eunice Kennedy Shriver Natl Inst C
TI Risk-adjusted models for adverse obstetric outcomes and variation in
risk-adjusted outcomes across hospitals
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Article
DE obstetrics; performance improvement; quality; risk adjustment
ID QUALITY IMPROVEMENT; CARE; HEMORRHAGE; INDICATORS; DELIVERY; DATABASE;
SOCIETY; SURGERY
AB OBJECTIVE: Regulatory bodies and insurers evaluate hospital quality using obstetrical outcomes, however meaningful comparisons should take preexisting patient characteristics into account. Furthermore, if risk-adjusted outcomes are consistent within a hospital, fewer measures and resources would be needed to assess obstetrical quality. Our objective was to establish risk-adjusted models for 5 obstetric outcomes and assess hospital performance across these outcomes.
STUDY DESIGN: We studied a cohort of 115,502 women and their neonates born in 25 hospitals in the United States from March 2008 through February 2011. Hospitals were ranked according to their unadjusted and risk-adjusted frequency of venous thromboembolism, postpartum hemorrhage, peripartum infection, severe perineal laceration, and a composite neonatal adverse outcome. Correlations between hospital risk-adjusted outcome frequencies were assessed.
RESULTS: Venous thromboembolism occurred too infrequently (0.03%; 95% confidence interval [CI], 0.02-0.04%) for meaningful assessment. Other outcomes occurred frequently enough for assessment (postpartum hemorrhage, 2.29%; 95% CI, 2.20-2.38, peripartum infection, 5.06%; 95% CI, 4.93e5.19, severe perineal laceration at spontaneous vaginal delivery, 2.16%; 95% CI, 2.06-2.27, neonatal composite, 2.73%; 95% CI, 2.63-2.84). Although there was high concordance between unadjusted and adjusted hospital rankings, several individual hospitals had an adjusted rank that was substantially different (as much as 12 rank tiers) than their unadjusted rank. None of the correlations between hospital-adjusted outcome frequencies was significant. For example, the hospital with the lowest adjusted frequency of peripartum infection had the highest adjusted frequency of severe perineal laceration.
CONCLUSION: Evaluations based on a single risk-adjusted outcome cannot be generalized to overall hospital obstetric performance.
C1 [Bailit, Jennifer L.] Case Western Reserve Univ, MetroHlth Med Ctr, Dept Obstet, Cleveland, OH 44106 USA.
[Bailit, Jennifer L.] Case Western Reserve Univ, MetroHlth Med Ctr, Dept Gynecol, Cleveland, OH 44106 USA.
[Grobman, William A.] Northwestern Univ, Chicago, IL 60611 USA.
[Wapner, Ronald J.] Columbia Univ, New York, NY USA.
[Varner, Michael W.] Univ Utah, Hlth Sci Ctr, Salt Lake City, UT USA.
[Thorp, John M.] Univ N Carolina, Chapel Hill, NC USA.
[Leveno, Kenneth J.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA.
[Caritis, Steve N.] Univ Pittsburgh, Pittsburgh, PA USA.
[Shubert, Phillip J.] Ohio State Univ, St Anns Hosp, Columbus, OH 43210 USA.
[Tita, Alan T.] Univ Alabama Birmingham, Birmingham, AL USA.
[Saade, George] Univ Texas Med Branch, Galveston, TX 77555 USA.
[Sorokin, Yoram] Wayne State Univ, Detroit, MI USA.
[Rouse, Dwight J.] Brown Univ, Providence, RI 02912 USA.
[Blackwell, Sean C.] Univ Texas Hlth Sci Ctr Houston, Childrens Mem Hermann Hosp, Houston, TX 77030 USA.
[Tolosa, Jorge E.] Oregon Hlth & Sci Univ, Portland, OR 97201 USA.
[Van Dorsten, J. Peter] Med Univ S Carolina, Charleston, SC 29425 USA.
[Rice, Madeline Murguia] George Washington Univ, Ctr Biostat, Washington, DC USA.
[Spong, Catherine Y.] 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, Cleveland, OH 44106 USA.
RI Romano, Patrick/N-4225-2014; Varner, Michael/K-9890-2013
OI Romano, Patrick/0000-0001-6749-3979; caritis, steve/0000-0002-2169-0712;
Varner, Michael/0000-0001-9455-3973
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development (NICHD) [HD21410, HD27869, HD27915, HD27917, HD34116,
HD34208, HD36801, HD40500, HD40512, HD40544, HD40545, HD40560, HD40485,
HD53097, HD53118]; National Center for Research Resources (NCRR) [UL1
RR024989, 5UL1 RR025764]
FX The project described was supported by grants from the Eunice Kennedy
Shriver National Institute of Child Health and Human Development (NICHD)
(HD21410, HD27869, HD27915, HD27917, HD34116, HD34208, HD36801, HD40500,
HD40512, HD40544, HD40545, HD40560, HD40485, HD53097, HD53118) and the
National Center for Research Resources (NCRR) (UL1 RR024989; 5UL1
RR025764) and its contents do not necessarily represent the official
views of the NICHD, NCRR, or National Institutes of Health.
NR 23
TC 5
Z9 5
U1 0
U2 6
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9378
EI 1097-6868
J9 AM J OBSTET GYNECOL
JI Am. J. Obstet. Gynecol.
PD NOV
PY 2013
VL 209
IS 5
AR 446.e1
DI 10.1016/j.ajog.2013.07.019
PG 30
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 242LP
UT WOS:000326243700017
PM 23891630
ER
PT J
AU Rom, S
Zuluaga-Ramirez, V
Dykstra, H
Reichenbach, NL
Pacher, P
Persidsky, Y
AF Rom, Slava
Zuluaga-Ramirez, Viviana
Dykstra, Holly
Reichenbach, Nancy L.
Pacher, Pal
Persidsky, Yuri
TI Selective Activation of Cannabinoid Receptor 2 in Leukocytes Suppresses
Their Engagement of the Brain Endothelium and Protects the Blood-Brain
Barrier
SO AMERICAN JOURNAL OF PATHOLOGY
LA English
DT Article
ID CENTRAL-NERVOUS-SYSTEM; TRANSENDOTHELIAL MIGRATION; INTEGRIN
CONFORMATION; MONOCYTE MIGRATION; HUMAN NEUTROPHILS; CELL-ACTIVATION;
POTENTIAL ROLE; IMMUNE CELLS; INFLAMMATION; ADHESION
AB Cannabinoid receptor 2 (CB2) is highly expressed in immune cells and stimulation decreases inflammatory responses. We tested the idea that selective CB2 activation in human monocytes suppresses their ability to engage the brain endothelium and migrate across the blood-brain barrier (BBB), preventing consequent injury. Intravital videomicroscopy was used to quantify adhesion of leukocytes to cortical vessels in lipopolysaccharide-induced neuroinflammation, after injection of ex vivo CB2-activated leukocytes into mice; CB2 agonists markedly decreased adhesion of ex vivo Labeled cells in vivo. In an in vitro BBB model, CB2 activation in monocytes Largely attenuated adhesion to and migration across monotayers of primary human brain microvascular endothelial cells and diminished BBB damage. CB2 stimulation in monocytes down-regulated active forms of integrins, lymphocyte function-associated antigen 1 (LFA-1), and very late antigen 4 (VLA-4). Cells treated with CB2 agonists exhibited increased phosphorylation levels of inhibitory sites of the actin-binding proteins cofilin and VASP, which are upstream regulators of conformational integrin changes. Up-regulated by relevant stimuli, Rac1 and RhoA were suppressed by CB2 agonists in monocytes. CB2 stimulation decreased formation of lamellipodia, which play a key role in monocyte migration. These results indicate that selective CB2 activation in Leukocytes decreases key steps in monocyte-BBB engagement, thus suppressing inflammatory leukocyte responses and preventing neuroinflammation.
C1 [Rom, Slava; Zuluaga-Ramirez, Viviana; Dykstra, Holly; Reichenbach, Nancy L.; Persidsky, Yuri] Temple Univ, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19140 USA.
[Pacher, Pal] NIAAA, Lab Physiol Studies, NIH, Bethesda, MD USA.
RP Persidsky, Y (reprint author), Temple Univ, Sch Med, Dept Pathol & Lab Med, 3401 N Broad St, Philadelphia, PA 19140 USA.
EM srom@temple.edu; persidsky@tuhs.temple.edu
RI Pacher, Pal/B-6378-2008
OI Pacher, Pal/0000-0001-7036-8108
FU NIH [R01 AA015913, R01 MH65151]; Intramural Research Program of the
NIH-NIAAA
FX Supported in part by NIH grants R01 AA015913 and R01 MH65151 (Y.P.) and
by the Intramural Research Program of the NIH-NIAAA (P.P.).
NR 55
TC 18
Z9 19
U1 1
U2 6
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 2013
VL 183
IS 5
BP 1548
EP 1558
DI 10.1016/j.ajpath.2013.07.033
PG 11
WC Pathology
SC Pathology
GA 246QE
UT WOS:000326553400021
PM 24055259
ER
PT J
AU Gallos, G
Remy, KE
Danielsson, J
Funayama, H
Fu, XW
Chang, HYS
Yim, P
Xu, DB
Emala, CW
AF Gallos, George
Remy, Kenneth E.
Danielsson, Jennifer
Funayama, Hiromi
Fu, Xiao Wen
Chang, Herng-Yu Sucie
Yim, Peter
Xu, Dingbang
Emala, Charles W., Sr.
TI Functional expression of the TMEM16 family of calcium-activated chloride
channels in airway smooth muscle
SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
LA English
DT Article
DE RT-PCR; MQAE; immunohistochemistry; electrophysiology; airway smooth
muscle
ID CA2+-ACTIVATED CL-CHANNELS; MUSCARINIC SIGNALING PATHWAY; PIG TRACHEAL
MYOCYTES; RABBIT COLONOCYTES; PRIMARY CULTURES; CA2+ SPARKS; CELLS;
CONTRACTION; CURRENTS; CANINE
AB Airway smooth muscle hyperresponsiveness is a key component in the pathophysiology of asthma. Although calcium-activated chloride channel (CaCC) flux has been described in many cell types, including human airway smooth muscle (HASM), the true molecular identity of the channels responsible for this chloride conductance remains controversial. Recently, a new family of proteins thought to represent the true CaCCs was identified as the TMEM16 family. This led us to question whether members of this family are functionally expressed in native and cultured HASM. We further questioned whether expression of these channels contributes to the contractile function of HASM. We identified the mRNA expression of eight members of the TMEM16 family in HASM cells and show immunohistochemical evidence of TMEM16A in both cultured and native HASM. Functionally, we demonstrate that the classic chloride channel inhibitor, 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB), inhibited halide flux in cultured HASM cells. Moreover, HASM cells displayed classical electrophysiological properties of CaCCs during whole cell electrophysiological recordings, which were blocked by using an antibody selective for TMEM16A. Furthermore, two distinct TMEM16A antagonists (tannic acid and benzbromarone) impaired a substance P-induced contraction in isolated guinea pig tracheal rings. These findings demonstrate that multiple members of this recently described family of CaCCs are expressed in HASM cells, they display classic electrophysiological properties of CaCCs, and they modulate contractile tone in airway smooth muscle. The TMEM16 family may provide a novel therapeutic target for limiting airway constriction in asthma.
C1 [Gallos, George; Danielsson, Jennifer; Fu, Xiao Wen; Chang, Herng-Yu Sucie; Yim, Peter; Xu, Dingbang; Emala, Charles W., Sr.] Columbia Univ Coll Phys & Surg, Dept Anesthesiol, New York, NY 10032 USA.
[Remy, Kenneth E.] NIH, Ctr Clin, Dept Crit Care, Bethesda, MD 20892 USA.
[Funayama, Hiromi] Tsurumi Univ, Sch Dent Med, Dept Pediat Dent, Tsurumi Ku, Yokohama, Kanagawa, Japan.
RP Gallos, G (reprint author), Columbia Univ Coll Phys & Surg, Dept Anesthesiol, 622 W 168th St P&S Box 46, New York, NY 10032 USA.
EM gg2125@columbia.edu
OI Remy, Kenneth/0000-0001-5222-9884
FU National Institutes of Health [GM093137, GM065281, GM008464]; Foundation
for Anesthesia Education and Research; National Center for Research
Resources [ULI RR 024156]
FX This work was supported by National Institutes of Health grants [G.
Gallos (GM093137); C. W. Emala (GM065281); and P. D. Yim (GM008464)];
The Foundation for Anesthesia Education and Research (H. S. Chang); and
the National Center for Research Resources ULI RR 024156.
NR 32
TC 14
Z9 15
U1 1
U2 9
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 1040-0605
EI 1522-1504
J9 AM J PHYSIOL-LUNG C
JI Am. J. Physiol.-Lung Cell. Mol. Physiol.
PD NOV
PY 2013
VL 305
IS 9
BP L625
EP L634
DI 10.1152/ajplung.00068.2013
PG 10
WC Physiology; Respiratory System
SC Physiology; Respiratory System
GA 246WK
UT WOS:000326571100005
PM 23997176
ER
PT J
AU Schnermann, J
Huang, YN
Mizel, D
AF Schnermann, Jurgen
Huang, Yuning
Mizel, Diane
TI Fluid reabsorption in proximal convoluted tubules of mice with gene
deletions of claudin-2 and/or aquaporin1
SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
LA English
DT Article
DE micropuncture; iothalamate; tubular fluid osmolarity; paracellular;
transcellular
ID GLOMERULAR-FILTRATION-RATE; TIGHT JUNCTION; LUMINAL HYPOTONICITY; WATER
PERMEABILITY; MEDIATED REDUCTION; MEMBRANE-PROTEINS; EPITHELIAL-CELLS;
NEPHRON FUNCTION; DEFICIENT MICE; DRIVING-FORCE
AB Deletions of claudin-2 (Cldn2) and aquaporin1 (AQP1) reduce proximal fluid reabsorption (PFR) by about 30% and 50%, respectively. Experiments were done to replicate these observations and to determine in AQP1/claudin-2 double knockout mice (DKO) if the effects of deletions of these established water pores are additive. PFR was determined in inactin/ketamine-anesthetized mice by free-flow micropuncture using single-nephron I-125-iothalamate (io) clearance. Animal means of PFR [% of glomerular filtration rate (GFR)] derived from TF/Piothalamate ratios in 12 mice in each of four groups [wild type (WT), Cldn2(-/-), AQP1(-/-), and DKO) were 45.8 +/- 0.85 (51 tubules), 35.4 +/- 1 (54 tubules; P < 0.01 vs. WT), 36.8 +/- 1 (63 tubules; P < 0.05 vs. WT), and 33.9 +/- 1.4 (69 tubules; P < 0.01 vs. WT). Kidney and single-nephron GFRs (SNGFR) were significantly reduced in all mutant strains. The direct relationship between PFR and SNGFR was maintained in mutant mice, but the slope of this relationship was reduced in the absence of Cldn2 and/or AQP1. Transtubular osmotic pressure differences were not different between WT and Cldn2(-/-) mice, but markedly increased in DKO. In conclusion, the deletion of Cldn2, AQP1, or of both Cldn2 and AQP1 reduces PFR by 22.7%, 19.6%, and 26%, respectively. Our data are consistent with an up to 25% paracellular contribution to PFR. The reduced osmotic water permeability caused by absence of AQP1 augments luminal hypotonicity. Aided by a fall in filtered load, the capacity of non-AQP1-dependent transcellular reabsorption is sufficient to maintain PFR without AQP1 and claudin-2 at 75% of control.
C1 [Schnermann, Jurgen; Huang, Yuning; Mizel, Diane] NIDDK, Kidney Dis Branch, NIH, Bethesda, MD 20892 USA.
RP Schnermann, J (reprint author), NIDDK, NIH, Bldg 10,Rm 4D51,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM jurgens@intra.niddk.nih.gov
FU Intramural Research Program of the National Institute of Diabetes and
Digestive and Kidney Diseases, National Institutes of Health
[DK-043408-12]
FX This work was supported by the Intramural Research Program of the
National Institute of Diabetes and Digestive and Kidney Diseases,
National Institutes of Health (DK-043408-12 to the Kidney Disease
Branch). The authors acknowledge valuable discussions with Drs. Mark
Knepper and Josephine Briggs.
NR 46
TC 20
Z9 20
U1 0
U2 9
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
PY 2013
VL 305
IS 9
BP F1352
EP F1364
DI 10.1152/ajprenal.00342.2013
PG 13
WC Physiology; Urology & Nephrology
SC Physiology; Urology & Nephrology
GA 247BI
UT WOS:000326588100012
PM 24049145
ER
PT J
AU Roth, MY
Ilani, N
Wang, C
Page, ST
Bremner, WJ
Swerdloff, RS
Dart, C
Sitruk-Ware, R
Kumar, N
Blithe, D
Amory, JK
AF Roth, M. Y.
Ilani, N.
Wang, C.
Page, S. T.
Bremner, W. J.
Swerdloff, R. S.
Dart, C.
Sitruk-Ware, R.
Kumar, N.
Blithe, D.
Amory, J. K.
TI Characteristics associated with suppression of spermatogenesis in a male
hormonal contraceptive trial using testosterone and Nestorone (R) gels
SO ANDROLOGY
LA English
DT Article
DE contraception; gonadotropins; nestorone; spermatogenesis; testosterone
ID NORMAL MEN; INDUCED AZOOSPERMIA; CHINESE MEN; UNDECANOATE; EFFICACY;
DISCONTINUATION; LEVONORGESTREL; GONADOTROPINS; COMBINATION; SECRETION
AB Development of a male hormonal contraceptive has been challenging ascribable to the failure to adequately suppress spermatogenesis in 5-10% of men. Methods to identify incomplete suppressors early in treatment might identify men most responsive to male hormonal contraceptives. We hypothesized that serum hormone and gonadotropin concentrations after 4weeks of transdermal treatment with testosterone and Nestorone in a contraceptive trial would be associated with suppression of sperm concentrations to <1million/mL after 24weeks. Indeed, luteinizing hormone or follicle-stimulating hormone concentrations greater than 1IU/L after 4weeks of transdermal testosterone/nestorone treatment were 97% sensitive for predicting failure to suppress spermatogenesis after 24weeks of treatment. Serum nestorone concentrations were significantly associated with suppression, but serum testosterone concentrations were not. Early suppression of gonadotropins is associated with, but does not ensure, adequate suppression of spermatogenesis. This information may allow for rapid identification of non-responders in male hormonal contraceptive trials.
C1 [Roth, M. Y.; Page, S. T.; Bremner, W. J.; Amory, J. K.] Univ Washington, Dept Internal Med, Seattle, WA 98195 USA.
[Ilani, N.; Wang, C.; Swerdloff, R. S.] Harbor UCLA Med Ctr, Dept Med, Div Endocrinol, Torrance, CA 90509 USA.
[Ilani, N.; Wang, C.; Swerdloff, R. S.] Los Angeles Biomed Res Inst, Torrance, CA USA.
[Dart, C.] Hlth Decis, Durham, NC USA.
[Sitruk-Ware, R.; Kumar, N.] Populat Council, Ctr Biomed Res, New York, NY 10021 USA.
[Blithe, D.] NICHHD, Contracept & Reprod Hlth Branch, NIH, Bethesda, MD 20892 USA.
RP Roth, MY (reprint author), Univ Washington, 1959 NE Pacific St,Box 357138, Seattle, WA 98195 USA.
EM mylang@u.washington.edu
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development [HHSN 2752004033691, HHSN 2751008060044U, U54 HD-42454, K12
HD053984]; Population Council; Endocrinology, Metabolism and Nutrition
Training Grant [T32 DK007571]; UCLA Clinical and Translational Science
Institute at Harbor-UCLA Medical Center [UL1TR000124]; Los Angeles
Biomedical Research Institute
FX The study was supported by the Eunice Kennedy Shriver National Institute
of Child Health and Human Development contracts HHSN 2752004033691 and
HHSN 2751008060044U, and the Population Council. The University of
Washington site was supported by the Eunice Kennedy Shriver National
Institute of Child Health and Human Development through cooperative
agreement U54 HD-42454 as part of the Cooperative Contraceptive Research
Centers Program and through K12 HD053984. The Los Angeles Center was
supported by the Endocrinology, Metabolism and Nutrition Training Grant
(T32 DK007571), and the UCLA Clinical and Translational Science
Institute (UL1TR000124) at Harbor-UCLA Medical Center and Los Angeles
Biomedical Research Institute. The authors acknowledge the gift of
testosterone gel through Paul Piette, MD, Besins Health Care
International; the help and assistance provided by Sharon Midler and her
team for monitoring the study at Health Decisions; Elizabeth Ruiz,
Xiao-Dan Han, Kathy Winter, Robert Bale Jr., Iris Nielsen, Connie Pete
and Dorothy McGuinness for their help in coordinating the study;
Christin Snyder, MD, for helping recruit and evaluate patients at the UW
site; Andrew Leung, HTC, Sima Baravarian, PhD and technologists of the
Hormone and Metabolic Research Laboratory at Los Angeles Biomedical
Research Institute at Harbor-UCLA Medical Center for all the hormone
analyses.
NR 27
TC 12
Z9 12
U1 1
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 2047-2919
EI 2047-2927
J9 ANDROLOGY-US
JI Andrology
PD NOV
PY 2013
VL 1
IS 6
BP 899
EP 905
DI 10.1111/j.2047-2927.2013.00135.x
PG 7
WC Andrology
SC Endocrinology & Metabolism
GA 239MT
UT WOS:000326030400016
PM 24123845
ER
PT J
AU Tsilidis, KK
Rohrmann, S
McGlynn, KA
Nyante, SJ
Lopez, DS
Bradwin, G
Feinleib, M
Joshu, CE
Kanarek, N
Nelson, WG
Selvin, E
Platz, EA
AF Tsilidis, K. K.
Rohrmann, S.
McGlynn, K. A.
Nyante, S. J.
Lopez, D. S.
Bradwin, G.
Feinleib, M.
Joshu, C. E.
Kanarek, N.
Nelson, W. G.
Selvin, E.
Platz, E. A.
TI Association between endogenous sex steroid hormones and inflammatory
biomarkers in US men
SO ANDROLOGY
LA English
DT Article
DE C-reactive protein; cross-sectional study; estradiol; testosterone;
white blood cell
ID C-REACTIVE PROTEIN; MIDDLE-AGED MEN; HYPOGONADAL MEN; PROSTATE-CANCER;
OLDER MEN; TESTOSTERONE REPLACEMENT; SERUM TESTOSTERONE; METABOLIC
SYNDROME; ANDROGEN RECEPTOR; ELDERLY-MEN
AB Sex steroid hormones and inflammatory biomarkers are both associated with the development and progression of chronic diseases, but their interrelationship is relatively uncharacterized. We examined the association of sex hormones and sex hormone-binding globulin (SHBG) with biomarkers of inflammation, C-reactive protein (CRP) and white blood cell (WBC) count. The study included data from 809 adult men in the National Health and Nutrition Examination Survey 1999-2004. Geometric means and 95% confidence intervals were estimated separately for CRP and WBC concentrations by sex steroid hormones and SHBG using weighted linear regression models. Higher concentrations of total (slope per one quintile in concentration, -0.18; p-trend, 0.001) and calculated free (slope, -0.13; p-trend, 0.03) testosterone were statistically significantly associated with lower concentrations of CRP, but not with WBC count. Men in the bottom quintile of total testosterone (3.3ng/mL), who might be considered to have clinically low testosterone, were more likely to have elevated CRP (3mg/L) compared with men in the top four quintiles (OR, 1.61; 95% CI, 1.00-2.61). Total and calculated free estradiol (E2) were positively associated with both CRP (Total E2: slope, 0.14; p-trend, <0.001; Free E2: slope, 0.15; p-trend, <0.001) and WBC (Total E2: slope, 0.02; p-trend, 0.08; Free E2: slope, 0.02; p-trend, 0.02) concentrations. SHBG concentrations were inversely associated with WBC count (slope, -0.03; p-trend, 0.04), but not with CRP. These cross-sectional findings are consistent with the hypothesis that higher androgen and lower oestrogen concentrations may have an anti-inflammatory effect in men.
C1 [Tsilidis, K. K.] Univ Ioannina, Sch Med, Dept Hyg & Epidemiol, GR-45110 Ioannina, Greece.
[Rohrmann, S.] Univ Zurich, Inst Social & Prevent Med, CH-8006 Zurich, Switzerland.
[McGlynn, K. A.; Nyante, S. J.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Lopez, D. S.] Univ Texas Sch Publ Hlth, Div Epidemiol, Houston, TX USA.
[Bradwin, G.] Harvard Univ, Sch Med, Dept Lab Med, Boston, MA USA.
[Bradwin, G.] Childrens Hosp, Boston, MA 02115 USA.
[Feinleib, M.; Joshu, C. E.; Selvin, E.; Platz, E. A.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Kanarek, N.; Nelson, W. G.; Platz, E. A.] Johns Hopkins Med Inst, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21205 USA.
[Kanarek, N.; Nelson, W. G.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Environm Hlth Sci, Baltimore, MD USA.
[Nelson, W. G.; Platz, E. A.] Johns Hopkins Med Inst, James Buchanan Brady Urol Inst, Baltimore, MD 21205 USA.
[Nelson, W. G.] Johns Hopkins Med Inst, Dept Oncol, Baltimore, MD 21205 USA.
[Nelson, W. G.] Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21205 USA.
[Nelson, W. G.] Johns Hopkins Med Inst, Dept Pharmacol & Mol Sci, Baltimore, MD 21205 USA.
[Nelson, W. G.] Johns Hopkins Med Inst, Dept Radiat Oncol, Baltimore, MD 21205 USA.
[Nelson, W. G.] Johns Hopkins Med Inst, Dept Mol Radiat Sci, Baltimore, MD 21205 USA.
[Selvin, E.; Platz, E. A.] Johns Hopkins Bloomberg Sch Publ Hlth, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD USA.
RP Tsilidis, KK (reprint author), Univ Ioannina, Sch Med, Dept Hyg & Epidemiol, Stavros Niarchos Av, GR-45110 Ioannina, Greece.
EM ktsilidi@cc.uoi.gr
FU Maryland Cigarette Restitution Fund at Johns Hopkins University
FX This is the 11th paper from the Hormone Demonstration Program, which was
funded by the Maryland Cigarette Restitution Fund at Johns Hopkins
University. The measurement of sex steroid hormone concentrations was
supported by the Intramural Research Program of the National Cancer
Institute, USA.
NR 46
TC 5
Z9 6
U1 2
U2 8
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 2047-2919
EI 2047-2927
J9 ANDROLOGY-US
JI Andrology
PD NOV
PY 2013
VL 1
IS 6
BP 919
EP 928
DI 10.1111/j.2047-2927.2013.00129.x
PG 10
WC Andrology
SC Endocrinology & Metabolism
GA 239MT
UT WOS:000326030400019
PM 24124163
ER
PT J
AU McManus, DD
Beaulieu, LM
Mick, E
Tanriverdi, K
Larson, MG
Keaney, JF
Benjamin, EJ
Freedman, JE
AF McManus, David D.
Beaulieu, Lea M.
Mick, Eric
Tanriverdi, Kahraman
Larson, Martin G.
Keaney, John F.
Benjamin, Emelia J.
Freedman, Jane E.
TI Relationship Among Circulating Inflammatory Proteins, Platelet Gene
Expression, and Cardiovascular Risk
SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
LA English
DT Article
DE cardiovascular disease; inflammation; mRNA platelets
ID C-REACTIVE PROTEIN; CORONARY-HEART-DISEASE; INTERCELLULAR-ADHESION
MOLECULE-1; GENOME-WIDE ASSOCIATION; BLOOD MONONUCLEAR-CELLS; TOLL-LIKE
RECEPTOR-4; INTERLEUKIN-6 RECEPTOR; METABOLIC SYNDROME; PLASMA; MEN
AB Objective Cardiovascular disease is a complex disorder influenced by interactions of genetic variants with environmental factors. However, there is no information from large community-based studies examining the relationship of circulating cell-specific RNA to inflammatory proteins. In light of the associations among inflammatory biomarkers, obesity, platelet function, and cardiovascular disease, we sought to examine the relationships of C-reactive protein (CRP) and interleukin-6 (IL-6) to the expression of key inflammatory transcripts in platelets.
Approach and Results We quantified circulating levels of CRP and IL-6 in 1625 participants of the Framingham Heart Study (FHS) Offspring cohort examination 8 (mean age, 66.66.6 years; 46% men). We measured the expression of 15 relevant genes by high-throughput quantitative reverse transcriptase polymerase chain reaction from platelet-derived RNA and used multivariable regression to relate serum concentrations of CRP and IL-6 with gene expression. Levels of CRP and IL-6 were associated with 10 of the 15 platelet-derived inflammatory transcripts, ALOX5, CRP, IFIT1, IL6, PTGER2, S100A9, SELENBP1, TLR2, TLR4, and TNFRSF1B (P<0.001). Associations between platelet mRNA expression with CRP and IL-6 persisted after multivariable adjustment for potentially confounding factors. Six genes positively associated with CRP or IL-6 in the FHS sample were also upregulated in megakaryocytes in response to CRP or IL-6 exposure.
Conclusions Our data highlight the strong connection between the circulating inflammatory biomarkers CRP and IL-6 and platelet gene expression, adjusting for cardiovascular disease risk factors. Our results also suggest that body weight may directly influence these associations.
C1 [McManus, David D.; Tanriverdi, Kahraman; Larson, Martin G.; Freedman, Jane E.] NHLBI, Framingham, MA USA.
[McManus, David D.; Tanriverdi, Kahraman; Larson, Martin G.; Freedman, Jane E.] Boston Univ, Framingham Heart Study, Framingham, MA USA.
[McManus, David D.; Beaulieu, Lea M.; Tanriverdi, Kahraman; Keaney, John F.; Freedman, Jane E.] Univ Massachusetts, Sch Med, Dept Med, Div Cardiol, Worcester, MA USA.
[McManus, David D.; Mick, Eric] Univ Massachusetts, Sch Med, Dept Quantitat Hlth Sci, Worcester, MA USA.
[Benjamin, Emelia J.] Boston Univ, Dept Med, Sect Cardiovasc Med, Boston, MA 02215 USA.
[Larson, Martin G.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA.
[Benjamin, Emelia J.] Boston Univ, Dept Med, Prevent Med Sect, Boston, MA 02215 USA.
[Benjamin, Emelia J.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02215 USA.
[Larson, Martin G.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA.
RP McManus, DD (reprint author), Univ Massachusetts, Sch Med, Div Cardiol, Worcester, MA 01655 USA.
EM mcmanusd@ummhc.org
OI Benjamin, Emelia/0000-0003-4076-2336; Mick, Eric/0000-0001-8505-8145
FU National Heart, Lung, and Blood Institute of the National Institutes of
Health (NIH) [N01-HC 25195, RFA-HL-12-008, RO1 HL087201A, 1RO1 HL64753,
R01 HL076784, 1 R01 AG028321]; NIH [1U01HL105268-01, KL2RR031981];
National Institute of Allergy and Infectious Disease [P01 AI078894]
FX This work was supported by N01-HC 25195, RFA-HL-12-008 (to J.E.
Freedman, E. Mick), RO1 HL087201A (to J.E. Freedman, K. Tanriverdi),
RFA-HL-12-008 (to J.E. Freedman), and 1RO1 HL64753, R01 HL076784, and 1
R01 AG028321 (to E.J. Benjamin) from the National Heart, Lung, and Blood
Institute of the National Institutes of Health (NIH). Partial salary
support is additionally provided by NIH grants 1U01HL105268-01 (to D. D.
McManus) and KL2RR031981 (to D. D. McManus). L. M. Beaulieu is supported
by P01 AI078894 from the National Institute of Allergy and Infectious
Disease.
NR 62
TC 15
Z9 15
U1 7
U2 16
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1079-5642
EI 1524-4636
J9 ARTERIOSCL THROM VAS
JI Arterioscler. Thromb. Vasc. Biol.
PD NOV
PY 2013
VL 33
IS 11
BP 2666
EP 2673
DI 10.1161/ATVBAHA.112.301112
PG 8
WC Hematology; Peripheral Vascular Disease
SC Hematology; Cardiovascular System & Cardiology
GA 244VQ
UT WOS:000326418700030
PM 23968978
ER
PT J
AU Aibara, D
Matsusue, K
Matsuo, K
Takiguchi, S
Gonzalez, FJ
Yamano, S
AF Aibara, Daisuke
Matsusue, Kimihiko
Matsuo, Kohei
Takiguchi, Soichi
Gonzalez, Frank J.
Yamano, Shigeru
TI Expression of Hepatic Fat-Specific Protein 27 Depends on the Specific
Etiology of Fatty Liver
SO BIOLOGICAL & PHARMACEUTICAL BULLETIN
LA English
DT Article
DE fat-specific protein 27; peroxisome proliferator-activated receptor;
fatty liver
ID ACTIVATED RECEPTOR-GAMMA; DIET-INDUCED STEATOHEPATITIS;
DNA-FRAGMENTATION-FACTOR; LEPTIN-DEFICIENT MICE; PPAR-GAMMA; CELL-DEATH;
ADIPOCYTE DIFFERENTIATION; EFFECTOR C; FSP27; STEATOSIS
AB Fat-specific protein 27 gene (FSP27), isolated by screening for genes specifically expressed in fully differentiated mouse adipocytes, belongs to the cell death-inducing DNA fragmentation factor, alpha subunit-like effector family. FSP27 is induced in not only adipose tissue but also the liver of ob/ob mice, and it promotes the development of fatty liver. The FSP27 gene is expressed in a fatty liver-specific manner and is not detected in the normal mouse liver. FSP27 expression is directly regulated by the induction of the hepatic peroxisome proliferator-activated receptor gamma (PPAR gamma) in ob/ob fatty liver. In the present study, expression of hepatic FSP27 mRNA was determined in non-genetic fatty liver models. The FSP27 gene was markedly induced in the high-fat- or methionine- and choline-deficient (MCD) diet-induced fatty liver, but it was not elevated in alcohol-induced fatty liver. Interestingly, the induction of FSP27 mRNA due to the MCD diet was independent of PPAR gamma levels and completely absent in the liver from PPAR gamma-null mice. These results suggest that FSP27 mRNA expression in the liver depends on the etiology of fatty liver.
C1 [Aibara, Daisuke; Matsusue, Kimihiko; Matsuo, Kohei; Yamano, Shigeru] Fukuoka Univ, Fac Pharmaceut Sci, Jonan Ku, Fukuoka 8140180, Japan.
[Takiguchi, Soichi] Natl Kyushu Canc Ctr, Inst Clin Res, Minami Ku, Fukuoka 8111395, Japan.
[Gonzalez, Frank J.] NCI, Lab Metab, NIH, Bethesda, MD 20892 USA.
RP Matsusue, K (reprint author), Fukuoka Univ, Fac Pharmaceut Sci, Jonan Ku, 8-19-1 Nanakuma, Fukuoka 8140180, Japan.
EM matsusuk@fukuoka-u.ac.jp
FU Mochida Memorial Foundation for Medical; KAKENHI [22590253]
FX This work was supported by a Grant from the Mochida Memorial Foundation
for Medical and from KAKENHI (22590253).
NR 31
TC 6
Z9 6
U1 0
U2 0
PU PHARMACEUTICAL SOC JAPAN
PI TOKYO
PA 2-12-15 SHIBUYA, SHIBUYA-KU, TOKYO, 150-0002, JAPAN
SN 0918-6158
J9 BIOL PHARM BULL
JI Biol. Pharm. Bull.
PD NOV
PY 2013
VL 36
IS 11
BP 1766
EP 1772
PG 7
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 244AQ
UT WOS:000326359900019
PM 24189421
ER
PT J
AU Chang, CM
Chia, VM
Gunter, MJ
Zanetti, KA
Ryan, BM
Goodman, JE
Harris, CC
Weissfeld, J
Huang, WY
Chanock, S
Yeager, M
Hayes, RB
Berndt, SI
AF Chang, Cindy M.
Chia, Victoria M.
Gunter, Marc J.
Zanetti, Krista A.
Ryan, Brid M.
Goodman, Julie E.
Harris, Curtis C.
Weissfeld, Joel
Huang, Wen-Yi
Chanock, Stephen
Yeager, Meredith
Hayes, Richard B.
Berndt, Sonja I.
CA Genetics Epidemiology Colorectal C
TI Innate immunity gene polymorphisms and the risk of colorectal neoplasia
SO CARCINOGENESIS
LA English
DT Article
ID FACTOR-KAPPA-B; COLON-CANCER; INTESTINAL TUMORIGENESIS;
BACTERIAL-INFECTIONS; RANDOMIZED-TRIALS; RECTAL-CANCER; METAANALYSIS;
ASSOCIATION; ASPIRIN; INFLAMMATION
AB Inherited variation in genes that regulate innate immunity and inflammation may contribute to colorectal neoplasia risk. To evaluate this association, we conducted a nested casecontrol study of 451 colorectal cancer cases, 694 colorectal advanced adenoma cases and 696 controls of European descent within the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. A total of 935 tag single-nucleotide polymorphisms (SNPs) in 98 genes were evaluated. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association with colorectal neoplasia. Sixteen SNPs were associated with colorectal neoplasia risk at P < 0.01, but after adjustment for multiple testing, only rs2838732 (ITGB2) remained suggestively associated with colorectal neoplasia (ORper T allele 0.68, 95% CI: 0.570.83, P 7.7 10(5), adjusted P 0.07). ITGB2 codes for the CD18 protein in the integrin beta chain family. The ITGB2 association was stronger for colorectal cancer (ORper T allele 0.41, 95% CI: 0.300.55, P 2.4 10(9)) than for adenoma (ORper T allele 0.84, 95%CI: 0.691.03, P 0.08), but it did not replicate in the validation study. The ITGB2 rs2838732 association was significantly modified by smoking status (P value for interaction 0.003). Among never and former smokers, it was inversely associated with colorectal neoplasia (ORper T allele 0.5, 95% CI: 0.370.69 and ORper T allele 0.72, 95% CI: 0.540.95, respectively), but no association was seen among current smokers. Other notable findings were observed for SNPs in BPI/LBP and MYD88. Although the results need to be replicated, our findings suggest that genetic variation in inflammation-related genes may be related to the risk of colorectal neoplasia.
C1 [Chang, Cindy M.; Chia, Victoria M.; Huang, Wen-Yi; Berndt, Sonja I.] NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20892 USA.
[Gunter, Marc J.] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Epidemiol & Biostat, London W2 1PG, England.
[Zanetti, Krista A.] Div Canc Control & Populat Sci, Host Susceptibil Factors Branch, Epidemiol & Genom Res Program, Rockville, MD 20892 USA.
[Zanetti, Krista A.; Ryan, Brid M.; Harris, Curtis C.] NCI, Human Carcinogenesis Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
[Goodman, Julie E.] Gradient Corp, Cambridge, MA 02138 USA.
[Weissfeld, Joel] Univ Pittsburgh, Inst Canc, Pittsburgh, PA 15232 USA.
[Chanock, Stephen] NCI, Lab Translat Genom, Div Canc Epidemiol & Genet, Gaithersburg, MD 20892 USA.
[Chanock, Stephen; Yeager, Meredith] NCI, Canc Genom Res Lab, SAIC Frederick, Frederick, MD 20892 USA.
[Hayes, Richard B.] NYU, Sch Med, Dept Populat Hlth, New York, NY 10016 USA.
RP Berndt, SI (reprint author), NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, DHHS, 9609 Med Ctr Dr,Room 6E610,MSC 9771, Bethesda, MD 20892 USA.
EM berndts@mail.nih.gov
RI KURY, Sebastien/G-5971-2015; Brenner, Hermann/B-4627-2017;
OI KURY, Sebastien/0000-0001-5497-0465; Brenner,
Hermann/0000-0002-6129-1572; Hayes, Richard/0000-0002-0918-661X
FU Intramural Research Program of the Division of Cancer Epidemiology and
Genetics; Center for Cancer Research at the National Cancer Institute,
National Institutes of Health; National Institutes of Health [U01
CA137088, R01 CA059045, U01 CA074783, R01 CA60987, K05 CA154337];
Canadian Institutes of Health Research; Canadian Cancer Society Research
Institute; Regional Council of Pays de la Loire; Groupement des
Entreprises Francaises dans la Lutte contre le Cancer (GEFLUC);
Association Anne de Bretagne Genetique; Ligue Regionale Contre le Cancer
(LRCC); German Research Council (Deutsche Forschungsgemeinschaft) [BR
1704/6-1, BR 1704/6-3, BR 1704/6-4, CH 117/1-1]; German Federal Ministry
of Education and Research [01KH0404, 01ER0814]; NHLBI; HHS
[HHSN268201100046C, HHSN268201100001C, HHSN268201100002C,
HHSN268201100003C, HHSN268201100004C, HHSN271201100004C]
FX Intramural Research Program of the Division of Cancer Epidemiology and
Genetics and the Center for Cancer Research at the National Cancer
Institute, National Institutes of Health; National Institutes of Health
(U01 CA137088, R01 CA059045) to The Genetics and Epidemiology of
Colorectal Cancer Consortium (GECCO). Funding for participating studies
from GECCO follows: ARCTIC: National Institutes of Health (U01
CA074783); a GL2 grant from the Canadian Institutes of Health Research;
and the Cancer Risk Evaluation (CaRE) Program grant from the Canadian
Cancer Society Research Institute. ASTERISK: a Hospital Clinical
Research Program (PHRC) and supported by the Regional Council of Pays de
la Loire, the Groupement des Entreprises Francaises dans la Lutte contre
le Cancer (GEFLUC), the Association Anne de Bretagne Genetique and the
Ligue Regionale Contre le Cancer (LRCC). COLO2&3: National Institutes of
Health (R01 CA60987). DACHS: German Research Council (Deutsche
Forschungsgemeinschaft, BR 1704/6-1, BR 1704/6-3, BR 1704/6-4 and CH
117/1-1) and the German Federal Ministry of Education and Research
(01KH0404 and 01ER0814). VITAL: National Institutes of Health (K05
CA154337). WHI: National Institutes of Health, NHLBI and HHS
(HHSN268201100046C, HHSN268201100001C, HHSN268201100002C,
HHSN268201100003C, HHSN268201100004C and HHSN271201100004C).
NR 52
TC 0
Z9 0
U1 0
U2 8
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0143-3334
EI 1460-2180
J9 CARCINOGENESIS
JI Carcinogenesis
PD NOV
PY 2013
VL 34
IS 11
BP 2512
EP 2520
DI 10.1093/carcin/bgt228
PG 9
WC Oncology
SC Oncology
GA 247WV
UT WOS:000326655200009
PM 23803696
ER
PT J
AU Nagababu, E
Rifkind, JM
AF Nagababu, Enika
Rifkind, Joseph M.
TI Routes for Formation of S-Nitrosothiols in Blood
SO CELL BIOCHEMISTRY AND BIOPHYSICS
LA English
DT Review
DE S-nitrosothiols; Nitric oxide; Blood; Hemoglobin; S-nitrosation;
Metalloproteins
ID NITRIC-OXIDE SYNTHASE; DINITROSYL-IRON COMPLEXES; VASCULAR
SMOOTH-MUSCLE; FREE-RADICAL MECHANISM; SERUM-ALBUMIN;
BIOLOGICAL-SYSTEMS; NITROGEN MONOXIDE; HUMAN PLASMA; RED-CELL; IN-VIVO
AB S-nitrosothiols (RSNO) are involved in post-translational modifications of many proteins analogous to protein phosphorylation. In addition, RSNO have many physiological roles similar to nitric oxide ((NO)-N-aEuro cent), which are presumably involving the release of (NO)-N-aEuro cent from the RSNO. However, the much longer life span in biological systems for RSNO than (NO)-N-aEuro cent suggests a dominant role for RSNO in mediating (NO)-N-aEuro cent bioactivity. RSNO are detected in plasma in low nanomolar levels in healthy human subjects. These RSNO are believed to be redirecting the (NO)-N-aEuro cent to the vasculature. However, the mechanism for the formation of RSNO in vivo has not been established. We have reviewed the reactions of (NO)-N-aEuro cent with oxygen, metalloproteins, and free radicals that can lead to the formation of RSNO and have evaluated the potential for each mechanism to provide a source for RSNO in vivo.
C1 [Nagababu, Enika; Rifkind, Joseph M.] NIA, Mol Dynam Sect, NIH, Baltimore, MD 21224 USA.
RP Nagababu, E (reprint author), NIA, Mol Dynam Sect, NIH, 251 Bayview Blvd,Rm 5B131, Baltimore, MD 21224 USA.
EM enikan@mail.nih.gov
FU Intramural Research Program of the National Institute on Aging, National
Institutes of Health, and USA
FX This research was supported by the Intramural Research Program of the
National Institute on Aging, National Institutes of Health, and USA.
NR 163
TC 8
Z9 8
U1 0
U2 20
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA
SN 1085-9195
EI 1559-0283
J9 CELL BIOCHEM BIOPHYS
JI Cell Biochem. Biophys.
PD NOV
PY 2013
VL 67
IS 2
SI SI
BP 385
EP 398
DI 10.1007/s12013-011-9321-2
PG 14
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA 242YP
UT WOS:000326282900018
PM 22161622
ER
PT J
AU Yang, CZ
Rahimpour, S
Yu, ACH
Lonser, RR
Zhuang, ZP
AF Yang, Chunzhang
Rahimpour, Shervin
Yu, Albert C. H.
Lonser, Russell R.
Zhuang, Zhengping
TI Regulation and dysregulation of astrocyte activation and implications in
tumor formation
SO CELLULAR AND MOLECULAR LIFE SCIENCES
LA English
DT Review
DE Glia; Astrocytoma; Gliosis; Brain tumor; Tumorigenesis; Central nervous
system
ID FIBRILLARY ACIDIC PROTEIN; HYPOXIA-INDUCIBLE FACTOR-1-ALPHA; ENDOTHELIAL
GROWTH-FACTOR; GLIOBLASTOMA STEM-CELLS; P2 PURINERGIC RECEPTORS;
CENTRAL-NERVOUS-SYSTEM; SPINAL-CORD-INJURY; NF-KAPPA-B; REACTIVE
ASTROCYTES; BETA-CATENIN
AB Astrocytic activation is a cellular response to disturbances of the central nervous system (CNS). Recent advances in cellular and molecular biology have demonstrated the remarkable changes in molecular signaling, morphology, and metabolism that occur during astrocyte activation. Based on these studies, it has become clear that the astrocyte activation process is regulated by a variety of signaling pathways, which result in metabolic support, wound healing and scar formation. While normal astrocyte activation pathways drive homeostasis and/or repair in the CNS, dysregulation of these pathways can lead to astrocyte abnormalities, including glioma formation with similar phenotypes as reactive astrocytes. We review the principle pathways responsible for astrocytic activation, as well as their potential contribution to tumor formation in the CNS.
C1 [Yang, Chunzhang; Rahimpour, Shervin; Lonser, Russell R.; Zhuang, Zhengping] NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA.
[Yu, Albert C. H.] Peking Univ, Hlth Sci Ctr, Sch Basic Med Sci,Minist Educ,Neurosci Res Inst, Dept Neurobiol,Minist Publ Hlth,Key Lab Neurosci, Beijing 100871, Peoples R China.
RP Yang, CZ (reprint author), NINDS, Surg Neurol Branch, NIH, Bldg 10,Room 3D20, Bethesda, MD 20892 USA.
EM yangc2@ninds.nih.gov; zhuangp@ninds.nih.gov
FU National Institute of Neurological Disorders and Stroke at the National
Institutes of Health
FX This research was supported by the intramural research program in the
National Institute of Neurological Disorders and Stroke at the National
Institutes of Health.
NR 116
TC 5
Z9 6
U1 1
U2 20
PU SPRINGER BASEL AG
PI BASEL
PA PICASSOPLATZ 4, BASEL, 4052, SWITZERLAND
SN 1420-682X
EI 1420-9071
J9 CELL MOL LIFE SCI
JI Cell. Mol. Life Sci.
PD NOV
PY 2013
VL 70
IS 22
BP 4201
EP 4211
DI 10.1007/s00018-013-1274-8
PG 11
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 239VD
UT WOS:000326052900001
PM 23420481
ER
PT J
AU Magill, SS
Klompas, M
Balk, R
Burns, SM
Deutschman, CS
Diekema, D
Fridkin, S
Greene, L
Guh, A
Gutterman, D
Hammer, B
Henderson, D
Hess, D
Hill, NS
Horan, T
Kollef, M
Levy, M
Septimus, E
VanAntwerpen, C
Wright, D
Lipsett, P
AF Magill, Shelley S.
Klompas, Michael
Balk, Robert
Burns, Suzanne M.
Deutschman, Clifford S.
Diekema, Daniel
Fridkin, Scott
Greene, Linda
Guh, Alice
Gutterman, David
Hammer, Beth
Henderson, David
Hess, Dean
Hill, Nicholas S.
Horan, Teresa
Kollef, Marin
Levy, Mitchell
Septimus, Edward
VanAntwerpen, Carole
Wright, Don
Lipsett, Pamela
TI Developing a New, National Approach to Surveillance for
Ventilator-Associated Events
SO CRITICAL CARE MEDICINE
LA English
DT Article
DE ventilator-associated pneumonia; intensive care unit; epidemiology;
public health; critical care; mechanical ventilation
ID DIAGNOSTIC-TECHNIQUES; RANDOMIZED-TRIAL; PNEUMONIA RATES; INFECTIONS;
VALIDATION; CRITERIA; DEFINITIONS
AB Objective: To develop and implement an objective, reliable approach to surveillance for ventilator-associated events in adult patients.
Design: The Centers for Disease Control and Prevention (CDC) convened a Ventilator-Associated Pneumonia (VAP) Surveillance Definition Working Group in September 2011. Working Group members included representatives of stakeholder societies and organizations and federal partners.
Main results: The Working Group finalized a three-tier, adult surveillance definition algorithm for ventilator-associated events. The algorithm uses objective, readily available data elements and can identify a broad range of conditions and complications occurring in mechanically ventilated adult patients, including but not limited to VAP. The first tier definition, ventilator-associated condition (VAC), identifies patients with a period of sustained respiratory deterioration following a sustained period of stability or improvement on the ventilator, defined by changes in the daily minimum fraction of inspired oxygen or positive end-expiratory pressure. The second tier definition, infection-related ventilator-associated complication (IVAC), requires that patients with VAC also have an abnormal temperature or white blood cell count, and be started on a new antimicrobial agent. The third tier definitions, possible and probable VAP, require that patients with IVAC also have laboratory and/or microbiological evidence of respiratory infection.
Conclusions: Ventilator-associated events surveillance was implemented in January 2013 in the CDC's National Healthcare Safety Network. Modifications to improve surveillance may be made as additional data become available and users gain experience with the new definitions.
C1 [Magill, Shelley S.; Fridkin, Scott; Guh, Alice; Horan, Teresa] Ctr Dis Control & Prevent, Div Healthcare Qual Promot, Atlanta, GA 30333 USA.
[Klompas, Michael] Harvard Univ, Sch Med, Dept Populat Med, Boston, MA USA.
[Klompas, Michael] Harvard Pilgrim Hlth Care Inst, Boston, MA USA.
[Klompas, Michael] Brigham & Womens Hosp, Infect Control Dept, Boston, MA 02115 USA.
[Klompas, Michael] Soc Healthcare Epidemiol Amer, Arlington, VA USA.
[Balk, Robert] Rush Univ, Sch Med, Div Pulm & Crit Care Med, Chicago, IL 60612 USA.
[Balk, Robert; Burns, Suzanne M.; Deutschman, Clifford S.; Gutterman, David; Hammer, Beth; Hill, Nicholas S.; Kollef, Marin; Levy, Mitchell; Lipsett, Pamela] Amer Thorac Soc, Amer Coll Chest Phys, Soc Crit Care Med, Crit Care Soc Collaborat Amer Assoc Crit Care Nur, New York, NY USA.
[Burns, Suzanne M.] Univ Virginia, Sch Nursing Crit & Acute Care, Charlottesville, VA USA.
[Deutschman, Clifford S.] Univ Penn, Perelman Sch Med, Dept Anesthesiol & Crit Care, Philadelphia, PA 19104 USA.
[Diekema, Daniel] Univ Iowa, Carver Coll Med, Div Infect Dis, Iowa City, IA USA.
[Diekema, Daniel] Healthcare Infect Control Practices Advisory Comm, Atlanta, GA USA.
[Greene, Linda] Rochester Gen Hlth Syst, Infect Prevent & Control Dept, Rochester, NY USA.
[Greene, Linda] Assoc Profess Infect Control & Epidemi, Washington, DC USA.
[Gutterman, David] Med Coll Wisconsin, Dept Med, Milwaukee, WI 53226 USA.
[Hammer, Beth] Med Coll Wisconsin, Zablocki Vet Adm Med Ctr, Dept Cardiol, Milwaukee, WI 53226 USA.
[Henderson, David] NIH, Hosp Epidemiol & Qual Improvement, Ctr Clin, Bethesda, MD 20892 USA.
[Hess, Dean] Massachusetts Gen Hosp, Dept Res Care, Boston, MA 02114 USA.
[Hess, Dean] Harvard Univ, Sch Med, Dept Anesthesia, Boston, MA 02115 USA.
[Hess, Dean] Amer Assoc Resp Care, Irving, TX USA.
[Hill, Nicholas S.] Tufts Med Ctr, Div Pulm & Crit Care Med, Boston, MA USA.
[Kollef, Marin] Washington Univ, Div Pulm & Crit Care Med, St Louis, MO USA.
[Levy, Mitchell] Brown Univ, Rhode Isl Hosp, Warren Alpert Med Sch, Divis Pulm Crit Care & Sleep, Providence, RI 02903 USA.
[Septimus, Edward] Texas A&M Univ, Ctr Sci, Dept Internal Med, College Stn, TX USA.
[Septimus, Edward] Infect Dis Soc Amer, Arlington, VA USA.
[VanAntwerpen, Carole] New York State Dept Hlth, Bur Healthcare Associated Infect, Albany, NY USA.
[VanAntwerpen, Carole] Council State & Terr Epidemiologists, Atlanta, GA USA.
[Wright, Don] US Dept HHS, Off Dis Prevent & Hlth Promot, Washington, DC 20201 USA.
[Lipsett, Pamela] Johns Hopkins Univ, Sch Med, Dept Surg Anesthesiol & Crit Care Med, Baltimore, MD USA.
RP Magill, SS (reprint author), Ctr Dis Control & Prevent, Div Healthcare Qual Promot, Atlanta, GA 30333 USA.
EM smagill@cdc.gov
OI Diekema, Daniel/0000-0003-1273-0724
FU Centers for Disease Control and Prevention (CDC); Centers for Disease
Control (CDC); U.S. Food and Drug Administration; Office of the National
Co-ordinator for Health IT; CDC; bioMerieux; National Institute of
General Medical Sciences; Merck; Cerexa; bioMeriuex; PurThread
Technologies; Pfizer; Society of Critical Care Medicine
FX The work described herein was supported by the Centers for Disease
Control and Prevention (CDC).; Dr. Klompas received grant support from
the Centers for Disease Control (CDC), U.S. Food and Drug
Administration, and the Office of the National Co-ordinator for Health
IT. Dr. Balk received grant support from the CDC and bioMerieux for
participation in the EPIC CAP study (CDC) and the Procalcitonin in ICU
antibiotic stewardship study (CDC and bioMerieux). Dr. Deutschman
received grant support from the National Institute of General Medical
Sciences. Dr. Diekema received grant support from Merck, Cerexa,
bioMeriuex, PurThread Technologies, and Pfizer.; Ms. Greene is employed
by the Rochester General Hospital. Dr. Lipsett has board membership with
the Society of Critical Care Medicine. Dr. Deutschman received a stipend
for his Presidency with the Society of Critical Care Medicine.
NR 37
TC 71
Z9 71
U1 1
U2 6
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0090-3493
EI 1530-0293
J9 CRIT CARE MED
JI Crit. Care Med.
PD NOV
PY 2013
VL 41
IS 11
BP 2467
EP 2475
DI 10.1097/CCM.0b013e3182a262db
PG 9
WC Critical Care Medicine
SC General & Internal Medicine
GA 243BO
UT WOS:000326291600032
PM 24162674
ER
PT J
AU Ito, T
Igarashi, H
Jensen, RT
AF Ito, Tetsuhide
Igarashi, Hisato
Jensen, Robert T.
TI Zollinger-Ellison syndrome: recent advances and controversies
SO CURRENT OPINION IN GASTROENTEROLOGY
LA English
DT Review
DE gastrin; gastrinoma; neuroendocrine tumor; pancreatic endocrine tumor
syndrome; Zollinger-Ellison syndrome
ID PANCREATIC NEUROENDOCRINE TUMORS; ENDOCRINE NEOPLASIA TYPE-1; LYMPH-NODE
GASTRINOMA; SOMATOSTATIN RECEPTOR SCINTIGRAPHY; PROTON PUMP INHIBITORS;
ISLET CELL TUMORS; ENETS CONSENSUS GUIDELINES; INSTITUTES-OF-HEALTH;
LONG-TERM; GEP-NETS
AB Purpose of reviewTo review the recent advances and current controversies in patients with Zollinger-Ellison syndrome (ZES).Recent findingsRecent advances in the management of ZES include: improved understanding of the pathogenesis of gastrinoma and pancreatic neuroendocrine tumors, new prognostic classification systems, new diagnostic algorithms, more sensitive localization studies, new treatment strategies including improved control of gastric acid secretion and role for surgery, and new approaches to patients with advanced disease. Controversies include: the best approach to a patient with hypergastrinemia suspected of possibly having ZES, the appropriate gastrin assay to use, the role of surgery in patients with ZES, especially those with multiple endocrine neoplasia type 1, and the precise order of therapeutic modalities in the treatment of patients with advanced disease.SummaryThis review updates clinicians regarding important advances and controversies required to optimally diagnose and manage patients with ZES.
C1 [Ito, Tetsuhide; Igarashi, Hisato] Kyushu Univ, Grad Sch Med Sci, Dept Med & Bioregulatory Sci, Higashi Ku, Fukuoka 812, Japan.
[Jensen, Robert T.] NIDDK, NIH, DDB, Bethesda, MD 20892 USA.
RP Jensen, RT (reprint author), NIDDK, NIH, DDB, Bldg 10,Rm 9C-103,10 Ctr Dr MSC 1804, Bethesda, MD 20892 USA.
EM robertj@bdg10.niddk.nih.gov
FU NIDDK, NIH
FX This research was supported in part by funding from the intramural
research program of the NIDDK, NIH.
NR 153
TC 13
Z9 13
U1 0
U2 4
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0267-1379
EI 1531-7056
J9 CURR OPIN GASTROEN
JI Curr. Opin. Gastroenterol.
PD NOV
PY 2013
VL 29
IS 6
BP 650
EP 661
DI 10.1097/MOG.0b013e328365efb1
PG 12
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 247AH
UT WOS:000326583900012
PM 24100728
ER
PT J
AU Leung, JM
Olivier, KN
AF Leung, Janice M.
Olivier, Kenneth N.
TI Nontuberculous mycobacteria: the changing epidemiology and treatment
challenges in cystic fibrosis
SO CURRENT OPINION IN PULMONARY MEDICINE
LA English
DT Review
DE cystic fibrosis; Mycobacterium abscessus; Mycobacterium avium complex;
nontuberculous mycobacteria
ID FATAL PULMONARY INFECTION; LUNG-TRANSPLANT; PSEUDOMONAS-AERUGINOSA;
MULTICENTER PREVALENCE; CLINICAL-SIGNIFICANCE; ADULT PATIENTS; AVIUM
COMPLEX; SP-NOV; ABSCESSUS; DISEASE
AB Purpose of reviewAlthough patients with cystic fibrosis (CF) face numerous infectious pathogens over the course of their lifespan, increasing attention has recently been paid to nontuberculous mycobacteria (NTM). As reported prevalence rates rise across many countries such as the United States, the ability to recognize disease caused by NTM and subsequently treat such disease has become increasingly important. This review summarizes new observations on the epidemiology of NTM in CF as well as key elements to consider during the treatment phase.Recent findingsAlthough overall rates of NTM isolation appear to be increasing, particular concern has focused on the emerging predominance of Mycobacterium abscessus. New data suggest that chronic macrolide therapy now part of routine CF care has contributed to this rise; however, these have yet to be confirmed prospectively. Transmission of M. abscessus between CF patients has also now been described through the use of genome sequencing. Although the greater virulence of M. abscessus makes it a challenging species to treat, identification of the subspecies type can now determine the presence of inducible macrolide resistance, thereby helping to guide treatment.SummaryGiven increasing prevalence rates, clinicians should maintain a high level of suspicion for NTM as disease-causing organisms in CF, particularly for M. abscessus. New knowledge regarding this species, however, can help to tailor appropriate therapy.
C1 [Leung, Janice M.] NIAID, Ctr Clin, Dept Crit Care Med, NIH, Bethesda, MD 20892 USA.
[Olivier, Kenneth N.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Olivier, KN (reprint author), NIH, Bldg 10,Room 12C103, Bethesda, MD 20892 USA.
EM olivierk@niaid.nih.gov
FU Division of Intramural Research, the National Institute of Allergy and
Infectious Diseases; National Institutes of Health Clinical Center
FX This work was supported in part by the Division of Intramural Research,
the National Institute of Allergy and Infectious Diseases, and the
National Institutes of Health Clinical Center.
NR 92
TC 33
Z9 33
U1 0
U2 18
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1070-5287
EI 1531-6971
J9 CURR OPIN PULM MED
JI Curr. Opin. Pulm. Med.
PD NOV
PY 2013
VL 19
IS 6
BP 662
EP 669
DI 10.1097/MCP.0b013e328365ab33
PG 8
WC Respiratory System
SC Respiratory System
GA 247FW
UT WOS:000326602900011
PM 24048085
ER
PT J
AU Spruijt-Metz, D
Belcher, BR
Hsu, YW
McClain, AD
Chou, CP
Nguyen-Rodriguez, S
Weigensberg, MJ
Goran, MI
AF Spruijt-Metz, Donna
Belcher, Britni R.
Hsu, Ya-Wen
McClain, Arianna D.
Chou, Chih-Ping
Nguyen-Rodriguez, Selena
Weigensberg, Marc J.
Goran, Michael I.
TI Temporal Relationship Between Insulin Sensitivity and the Pubertal
Decline in Physical Activity in Peripubertal Hispanic and African
American Females
SO DIABETES CARE
LA English
DT Article
ID AGE-RELATED DECLINE; METABOLIC SYNDROME; UNITED-STATES; ENERGY
HOMEOSTASIS; YOUTH; RESISTANCE; CHILDREN; GLUCOSE; ACCELEROMETER;
RESPONSIVITY
AB OBJECTIVELittle attention has been paid to possible intrinsic biological mechanisms for the decline in physical activity that occurs during puberty. This longitudinal observational study examined the association between baseline insulin sensitivity (SI) and declines in physical activity and increases in sedentary behavior in peripubertal minority females over a year.RESEARCH DESIGN AND METHODSParticipants were Hispanic and African American girls (n = 55; 76% Hispanic; mean age 9.4 years; 36% obese). SI and other insulin indices were measured at baseline using the frequently sampled intravenous glucose tolerance test. Physical activity was measured on a quarterly basis by accelerometry and self-report.RESULTSPhysical activity declined by 25% and time spent in sedentary behaviors increased by approximate to 13% over 1 year. Lower baseline SI predicted the decline in physical activity measured by accelerometry, whereas higher baseline acute insulin response to glucose predicted the decline in physical activity measured by self-report. Time spent in sedentary behavior increased by similar to 13% over 1 year, and this was predicted by lower baseline SI. All models controlled for adiposity, age, pubertal stage, and ethnicity.CONCLUSIONSWhen evaluated using a longitudinal design with strong outcome measures, this study suggests that lower baseline SI predicts a greater decline in physical activity in peripubertal minority females.
C1 [Spruijt-Metz, Donna; Chou, Chih-Ping; Weigensberg, Marc J.; Goran, Michael I.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA.
[Belcher, Britni R.] NCI, Appl Res Program, Risk Factor Monitoring & Methods Branch, Canc Prevent Div, Bethesda, MD 20892 USA.
[Hsu, Ya-Wen] Chia Nan Univ Pharm & Sci, Dept Hosp & Hlth Care Adm, Coll Hlth & Informat, Tainan, Taiwan.
[McClain, Arianna D.] Stanford Univ, Stanford Prevent Res Ctr, Sch Med, Stanford, CA 94305 USA.
[Nguyen-Rodriguez, Selena] Calif State Univ Long Beach, Dept Hlth Sci, Coll Hlth & Human Serv, Long Beach, CA 90840 USA.
[Weigensberg, Marc J.] Univ So Calif, Dept Pediat, Los Angeles, CA 90089 USA.
RP Spruijt-Metz, D (reprint author), Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA.
EM dmetz@usc.edu
FU University of Southern California Center for Transdisciplinary Research
on Energetics and Cancer [U54 CA 116848]
FX This work was supported by the University of Southern California Center
for Transdisciplinary Research on Energetics and Cancer (grant U54 CA
116848).
NR 39
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Z9 2
U1 0
U2 1
PU AMER DIABETES ASSOC
PI ALEXANDRIA
PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA
SN 0149-5992
EI 1935-5548
J9 DIABETES CARE
JI Diabetes Care
PD NOV
PY 2013
VL 36
IS 11
BP 3739
EP 3745
DI 10.2337/dc13-0083
PG 7
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 242VZ
UT WOS:000326274100061
PM 23846812
ER
PT J
AU Maldonado-Baez, L
Williamson, C
Donaldson, JG
AF Maldonado-Baez, Lymarie
Williamson, Chad
Donaldson, Julie G.
TI Clathrin-independent endocytosis: A cargo-centric view
SO EXPERIMENTAL CELL RESEARCH
LA English
DT Review
DE Endocytosis; Clathrin-independent endocytosis; Plasma membrane protein;
Protein sorting; Nutrient transporters; Ion channels; Cell adhesion
molecules
ID INTERCELLULAR-ADHESION MOLECULE-1; DENSITY-LIPOPROTEIN RECEPTOR;
FIBROBLAST-GROWTH-FACTOR; AMINO-ACID-TRANSPORT; MHC CLASS-II;
CYTOPLASMIC DOMAINS; ENDOSOMAL TRANSPORT; MEMBRANE-TRANSPORT; RECYCLING
PATHWAY; SURFACE-RECEPTOR
AB Clathrin-independent endocytosis occurs in all cells and interest in this mode of cellular entry has grown. Although this form of endocytosis was first described for entry of bacterial toxins, here we focus our attention on the endogenous cell surface "cargo" proteins that enter cells by this mechanism. The cargo proteins entering by this mechanism are varied and include nutrient transporters, ion channels, cell adhesion molecules and proteins associated with the immune system. Despite the apparent lack of selection at the cell surface, we provide some examples of specific sorting of these cargo proteins after entry, leading to distinct itineraries and cellular fates. Published by Elsevier Inc.
C1 [Maldonado-Baez, Lymarie; Williamson, Chad; Donaldson, Julie G.] NHLBI, Cell Biol & Physiol Ctr, NIH, Bethesda, MD 20892 USA.
RP Donaldson, JG (reprint author), NHLBI, NIH, Bld 50,Rm 2503, Bethesda, MD 20892 USA.
EM donaldsonj@helix.nih.gov
FU Intramural NIH HHS [ZIA HL006130-03, ZIA HL006060-04]
NR 115
TC 30
Z9 30
U1 1
U2 23
PU ELSEVIER INC
PI SAN DIEGO
PA 525 B STREET, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0014-4827
EI 1090-2422
J9 EXP CELL RES
JI Exp. Cell Res.
PD NOV 1
PY 2013
VL 319
IS 18
BP 2759
EP 2769
DI 10.1016/j.yexcr.2013.08.008
PG 11
WC Oncology; Cell Biology
SC Oncology; Cell Biology
GA 245BA
UT WOS:000326432700001
PM 23954817
ER
PT J
AU Kilari, RS
Weaver, JD
Shears, SB
Safrany, ST
AF Kilari, Rajagopal S.
Weaver, Jeremy D.
Shears, Stephen B.
Safrany, Stephen T.
TI Understanding inositol pyrophosphate metabolism and function: Kinetic
characterization of the DIPPs
SO FEBS LETTERS
LA English
DT Article
DE Nudix; Diphosphoinositol; Phosphohydrolase; CDK5RAP1
ID DIPHOSPHOINOSITOL POLYPHOSPHATE PHOSPHOHYDROLASE;
SCHIZOSACCHAROMYCES-POMBE; BINDING; PROTEIN; INHIBITOR; CDK5;
IDENTIFICATION; HYDROLASES; FAMILY; GROWTH
AB We illuminate the metabolism and the cell-signaling activities of inositol pyrophosphates, by showing that regulation of yeast cyclin-kinase by 1-InsP(7) is not conserved for mammalian CDK5, and by kinetically characterizing Ddp1p/DIPP-mediated dephosphorylation of 1-InsP(7), 5-InsP(7) and InsP(8). Each phosphatase exhibited similar Km values for every substrate (range: 35-148 nM). The rank order of k(cat) values (1-InsP(7) > 5-InsP(7) = InsP(8)) was identical for each enzyme, although DIPP1 was 10- to 60-fold more active than DIPP2 alpha/beta and DIPP3 alpha/beta. We demonstrate InsP(8) dephosphorylation preferentially progresses through 1-InsP(7). Conversely, we conclude that the more metabolically and functionally significant steady-state route of InsP(8) synthesis proceeds via 5-InsP(7). Published by Elsevier B. V. on behalf of the Federation of European Biochemical Societies.
C1 [Kilari, Rajagopal S.; Safrany, Stephen T.] Wolverhampton Univ, Fac Sci & Engn, Dept Pharm, Wolverhampton WV1 1LY, England.
[Weaver, Jeremy D.; Shears, Stephen B.] NIEHS, Inositide Signaling Grp, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA.
RP Shears, SB (reprint author), NIEHS, Inositide Signaling Grp, Lab Signal Transduct, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
EM shears@niehs.nih.gov; S.Safrany@wlv.ac.uk
FU University of Wolverhampton's Research Institute of Healthcare Science;
Intramural Research Program of the NIH, National Institute of
Environmental Health Sciences
FX RS Kilari was supported by a PhD studentship from the University of
Wolverhampton's Research Institute of Healthcare Science. This research
was also supported by the Intramural Research Program of the NIH,
National Institute of Environmental Health Sciences.
NR 30
TC 18
Z9 18
U1 1
U2 11
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0014-5793
EI 1873-3468
J9 FEBS LETT
JI FEBS Lett.
PD NOV 1
PY 2013
VL 587
IS 21
BP 3464
EP 3470
DI 10.1016/j.febslet.2013.08.035
PG 7
WC Biochemistry & Molecular Biology; Biophysics; Cell Biology
SC Biochemistry & Molecular Biology; Biophysics; Cell Biology
GA 238VE
UT WOS:000325978700016
PM 24021644
ER
PT J
AU Hill, MJ
Whitcomb, BW
Lewis, TD
Wu, M
Terry, N
DeCherney, AH
Levens, ED
Propst, AM
AF Hill, Micah J.
Whitcomb, Brian W.
Lewis, Terrence D.
Wu, Mae
Terry, Nancy
DeCherney, Alan H.
Levens, Eric D.
Propst, Anthony M.
TI Progesterone luteal support after ovulation induction and intrauterine
insemination: a systematic review and meta-analysis
SO FERTILITY AND STERILITY
LA English
DT Review
DE Progesterone; luteal support; ovulation induction; intrauterine
insemination
ID CLOMIPHENE CITRATE; MIDLUTEAL PHASE; LUTEINIZING-HORMONE; OVARIAN
STIMULATION; PREGNANCY RATES; CORPUS-LUTEUM; GNRH AGONIST; CYCLES;
IMPLANTATION; ESTRADIOL
AB Objective: To evaluate the effect of luteal phase P support after ovulation induction IUI.
Design: A systematic review and meta-analysis.
Setting: Not applicable.
Patient(s): Undergoing ovulation induction IUI.
Intervention(s): Any form of exogenous P in ovulation induction IUI cycles.
Main Outcome Measure(s): Clinical pregnancy and live birth.
Result(s): Five trials were identified that met inclusion criteria and comprised 1,298 patients undergoing 1,938 cycles. Clinical pregnancy (odds ratio [OR] 1.47, 95% confidence interval [CI] 1.15-1.98) and live birth (OR 2.11, 95% CI 1.21-3.67) were more likely in P-supplemented patients. These findings persisted in analyses evaluating per IUI cycle, per patient, and first cycle only data. In subgroup analysis, patients receiving gonadotropins for ovulation induction had the most increase in clinical pregnancy with P support (OR 1.77, 95% CI 1.20-2.6). Conversely, patients receiving clomiphene citrate (CC) for ovulation induction showed no difference in clinical pregnancy with P support (OR 0.89, 95% CI 0.47-1.67).
Conclusion(s): Progesterone luteal phase support may be of benefit to patients undergoing ovulation induction with gonadotropins in IUI cycles. Progesterone support did not benefit patients undergoing ovulation induction with CC, suggesting a potential difference in endogenous luteal phase function depending on the method of ovulation induction. (C) 2013 by American Society for Reproductive Medicine.
C1 [Hill, Micah J.; DeCherney, Alan H.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD 20892 USA.
[Whitcomb, Brian W.] Univ Massachusetts, Dept Biostat & Epidemiol, Sch Publ Hlth & Hlth Sci, Amherst, MA 01003 USA.
[Lewis, Terrence D.; Wu, Mae; Propst, Anthony M.] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA.
[Terry, Nancy] Natl Inst Hlth Lib, Bethesda, MD USA.
[Levens, Eric D.] Shady Grove Fertil Reprod Sci Ctr, Rockville, MD USA.
RP Hill, MJ (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA.
EM hillmicah@mail.nih.gov
FU Program in Reproductive and Adult Endocrinology, National Institute of
Child Health and Human Development, National Institutes of Health,
Bethesda, Maryland
FX Supported, in part, by the Program in Reproductive and Adult
Endocrinology, National Institute of Child Health and Human Development,
National Institutes of Health, Bethesda, Maryland.
NR 30
TC 16
Z9 18
U1 0
U2 9
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0015-0282
EI 1556-5653
J9 FERTIL STERIL
JI Fertil. Steril.
PD NOV
PY 2013
VL 100
IS 5
BP 1373
EP +
DI 10.1016/j.fertnstert.2013.06.034
PG 14
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 242IU
UT WOS:000326233700039
PM 23876537
ER
PT J
AU Bukh, J
Lanford, RE
Purcell, RH
AF Bukh, Jens
Lanford, Robert E.
Purcell, Robert H.
TI Persistent Human Hepatitis B Virus Infection in Cynomolgus Monkeys: A
Novel Animal Model in the Search for a Cure?
SO HEPATOLOGY
LA English
DT Editorial Material
ID WOOLLY MONKEY; LIVER; HEPADNAVIRUS
C1 [Bukh, Jens] Copenhagen Univ Hosp, Dept Infect Dis, Copenhagen Hepatitis C Program CO HEP, DK-2650 Hvidovre, Denmark.
[Bukh, Jens] Copenhagen Univ Hosp, Clin Res Ctr, DK-2650 Hvidovre, Denmark.
[Bukh, Jens] Univ Copenhagen, Fac Hlth & Med Sci, Dept Int Hlth Immunol & Microbiol, Copenhagen, Denmark.
[Lanford, Robert E.] Southwest Natl Primate Res Ctr, Texas Biomed Res Inst, Dept Virol & Immunol, San Antonio, TX USA.
[Purcell, Robert H.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Bukh, J (reprint author), Copenhagen Univ Hosp, Dept Infect Dis, Copenhagen Hepatitis C Program CO HEP, Kettegaard Alle 30, DK-2650 Hvidovre, Denmark.
EM jbukh@sund.ku.dk
FU Intramural NIH HHS [Z01 AI000311-27]; NIH HHS [P51 OD011133]
NR 20
TC 3
Z9 4
U1 1
U2 2
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 2013
VL 58
IS 5
BP 1533
EP 1536
DI 10.1002/hep.26560
PG 4
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 243OZ
UT WOS:000326327600004
PM 23775673
ER
PT J
AU Noureddin, M
Wright, EC
Alter, HJ
Clark, S
Thomas, E
Chen, R
Zhao, XC
Conry-Cantilena, C
Kleiner, DE
Liang, TJ
Ghany, MG
AF Noureddin, Mazen
Wright, Elizabeth C.
Alter, Harvey J.
Clark, Shauna
Thomas, Emmanuel
Chen, Richard
Zhao, Xiongce
Conry-Cantilena, Cathy
Kleiner, David E.
Liang, T. Jake
Ghany, Marc G.
TI Association of IL28B Genotype With Fibrosis Progression and Clinical
Outcomes in Patients With Chronic Hepatitis C: A Longitudinal Analysis
SO HEPATOLOGY
LA English
DT Article
ID GENOME-WIDE-ASSOCIATION; INDUCED VIRAL CLEARANCE; VIRUS-RELATED
CIRRHOSIS; GENETIC-VARIATION; INTERFERON; INFECTION; PEGINTERFERON;
EPIDEMIOLOGY; INFLAMMATION; FREQUENCY
AB Interleukin (IL)28B polymorphisms are associated with spontaneous clearance of hepatitis C virus (HCV) infection and response to therapy. Whether IL28B genotype affects fibrosis progression or clinical outcome is unclear. Our aim was to study the relationship between IL28B genotype and both histological and clinical outcomes in patients with chronic hepatitis C (CHC). Hepatic fibrosis was scored using the Ishak (0-6) scale; progression was defined as a 2-point increase in Ishak score between biopsies. Multiple logistic and Cox regressions were used to identify variables associated with fibrosis progression. In all, 1,483 patients were included in a baseline cross-sectional analysis, from which 276 were eligible for a paired biopsy analysis (median time between biopsies 4 years), and 400 for a clinical outcome analysis. At baseline biopsy, patients with IL28B CC genotype had significantly higher portal inflammation (2.4 versus 2.2) and alanine aminotransferase (ALT) levels (133 versus 105 U/L; P < 0.05 for all). In the paired biopsy analysis, there was no difference in the frequency of fibrosis progression between patients with IL28B CC and non-CC genotypes (17% versus 23%). In logistic regression, only higher baseline alkaline phosphatase, lower platelets, and greater hepatic steatosis were associated with fibrosis progression. Patients with IL28B CC were twice as likely to develop adverse clinical outcomes compared to non-CC (32% versus 16%; P = 0.007). Conclusion: IL28B CC genotype was associated with greater hepatic necroinflammation, higher ALT, and worse clinical outcomes in CHC patients. This suggests that IL28B CC is associated with a state of enhanced immunity that, on the one hand, can promote viral clearance, but alternately can increase necroinflammation and hepatic decompensation without enhancing fibrosis progression. (Hepatology 2013;58:1548-1557)
C1 [Noureddin, Mazen; Clark, Shauna; Thomas, Emmanuel; Liang, T. Jake; Ghany, Marc G.] Natl Inst Diabet & Digest & Kidney Dis, Liver Dis Branch, NIH, Bethesda, MD 20892 USA.
[Wright, Elizabeth C.; Chen, Richard; Zhao, Xiongce] Natl Inst Diabet & Digest & Kidney Dis, Off Director, NIH, Bethesda, MD 20892 USA.
[Alter, Harvey J.; Conry-Cantilena, Cathy] NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA.
[Kleiner, David E.] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA.
RP Ghany, MG (reprint author), Natl Inst Diabet & Digest & Kidney Dis, Liver Dis Branch, NIH, Bldg 10,Rm 9B-16,10 Ctr Dr,MSC 1800, Bethesda, MD 20892 USA.
EM marcg@intra.niddk.nih.gov
OI Kleiner, David/0000-0003-3442-4453
FU Intramural NIH HHS [ZIA DK075009-07]
NR 31
TC 49
Z9 50
U1 0
U2 2
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 2013
VL 58
IS 5
BP 1548
EP 1557
DI 10.1002/hep.26506
PG 10
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 243OZ
UT WOS:000326327600006
PM 23703931
ER
PT J
AU Pedersen, J
Carlsen, THR
Prentoe, J
Ramirez, S
Jensen, TB
Forns, X
Alter, H
Foung, SKH
Law, M
Gottwein, J
Weis, N
Bukh, J
AF Pedersen, Jannie
Carlsen, Thomas H. R.
Prentoe, Jannick
Ramirez, Santseharay
Jensen, Tanja B.
Forns, Xavier
Alter, Harvey
Foung, Steven K. H.
Law, Mansun
Gottwein, Judith
Weis, Nina
Bukh, Jens
TI Neutralization Resistance of Hepatitis C Virus Can Be Overcome by
Recombinant Human Monoclonal Antibodies
SO HEPATOLOGY
LA English
DT Article
ID CELL-CULTURE SYSTEMS; GENOTYPE 2A; INFECTION; SEQUENCE; MUTATIONS;
SUBTYPE; FAILURE; GENOME; REPLICATION; CHIMPANZEES
AB Immunotherapy and vaccine development for hepatitis C virus (HCV) will depend on broadly reactive neutralizing antibodies (NAbs). However, studies in infectious strain JFH1-based culture systems expressing patient-derived Core-NS2 proteins have suggested neutralization resistance for specific HCV strains, in particular, of genotype 2. To further examine this phenomenon, we developed a panel of HCV genotype 2 recombinants for testing of sensitivity to neutralization by chronic-phase patient sera and lead human monoclonal antibodies (HMAbs). The novel Core-NS2 recombinants, with patient-derived genotype 2a (strain T9), 2b (strains DH8 and DH10), and 2c (strain S83) consensus sequences, were viable in Huh7.5 hepatoma cells without requirement for adaptive mutations, reaching HCV infectivity titers of 3.9-4.5 log(10) focus-forming units per milliliter. In in vitro neutralization assays, we demonstrated that the novel genotype 2 viruses as well as prototype strains J6/JFH1(2a) and J8/JFH1(2b), all with authentic envelope proteins, were resistant to neutralization by genotype 2a, 2b, 2c, 2j, 2i, and 2q patient sera. However, these patient sera had high titers of HCV-specific NAbs, because they efficiently reduced the infectivity of J6(2a) and J8(2b) with deleted hypervariable region 1. The genotype 2a, 2b, and 2c viruses, found resistant to polyclonal patient sera neutralization, were efficiently neutralized by two lead HMAbs (AR4A and HC84.26). Conclusion: Using novel 2a, 2b, and 2c cell-culture systems, expressing authentic envelope proteins, we demonstrated resistance of HCV to patient-derived polyclonal high-titer NAbs. However, the same genotype 2 culture viruses were all sensitive to HMAbs recognizing conformational epitopes, indicating that neutralization resistance of HCV can be overcome by applying recombinant antibodies. These findings have important implications for HCV immunotherapy and vaccine development. (Hepatology 2013;58:1587-1597)
C1 [Pedersen, Jannie; Carlsen, Thomas H. R.; Prentoe, Jannick; Ramirez, Santseharay; Jensen, Tanja B.; Gottwein, Judith; Bukh, Jens] Copenhagen Univ Hosp, Dept Infect Dis, Copenhagen Hepatitis Program CO HEP C, DK-2650 Hvidovre, Denmark.
[Pedersen, Jannie; Carlsen, Thomas H. R.; Prentoe, Jannick; Ramirez, Santseharay; Jensen, Tanja B.; Gottwein, Judith; Bukh, Jens] Copenhagen Univ Hosp, Clin Res Ctr, DK-2650 Hvidovre, Denmark.
[Pedersen, Jannie; Carlsen, Thomas H. R.; Prentoe, Jannick; Ramirez, Santseharay; Jensen, Tanja B.; Gottwein, Judith; Bukh, Jens] Univ Copenhagen, Fac Hlth & Med Sci, Dept Int Hlth Immunol & Microbiol, Copenhagen, Denmark.
[Forns, Xavier] CIBERehd, IDIBAPS, Hosp Clin Barcelona, Liver Unit, Barcelona, Spain.
[Forns, Xavier] Univ Barcelona, Barcelona, Spain.
[Alter, Harvey] NIH, Dept Transfus Med, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA.
[Foung, Steven K. H.] Stanford Univ, Dept Pathol, Sch Med, Stanford, CA 94305 USA.
[Law, Mansun] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA.
[Weis, Nina; Bukh, Jens] Copenhagen Univ Hosp, Dept Infect Dis, DK-2650 Hvidovre, Denmark.
[Weis, Nina] Univ Copenhagen, Fac Hlth & Med Sci, Dept Clin Med, Copenhagen, Denmark.
RP Bukh, J (reprint author), Copenhagen Univ Hosp, Dept Infect Dis, Kettegaard Alle 30, DK-2650 Hvidovre, Denmark.
EM jbukh@sund.ku.dk
RI Ramirez, Santseharay/R-9257-2016;
OI Ramirez, Santseharay/0000-0003-3699-1814; Pedersen,
Jannie/0000-0003-2822-3014; Prentoe, Jannick/0000-0003-2203-9478
FU Lundbeck Foundation; Danish Cancer Society; Novo Nordisk Foundation;
RegionH Research Fund; The Danish Agency for Science Technology and
Innovation; Faculty of Health and Medical Sciences, University of
Copenhagen; Danish Council for Independent Research (FSS); U.S. National
Institutes of Health [AI79031]
FX This work was supported by the Lundbeck Foundation (to J.G. and J.B.),
the Danish Cancer Society (to J.G. and J.B.), the Novo Nordisk
Foundation (to J.G. and J.B.), the RegionH Research Fund (to J.B.), The
Danish Agency for Science Technology and Innovation (to J.P. and N.W.),
and Ph.D. stipends from the Faculty of Health and Medical Sciences,
University of Copenhagen (to T. H. R. C., J.P. R., and T.B.J.). J.P. R.
and S. R. are the recipients of Individual Postdoctoral Stipends from
the Danish Council for Independent Research (FSS). M. L. is supported by
the U.S. National Institutes of Health (grant no.: AI79031).
NR 37
TC 18
Z9 18
U1 0
U2 5
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 2013
VL 58
IS 5
BP 1587
EP 1597
DI 10.1002/hep.26524
PG 11
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 243OZ
UT WOS:000326327600010
PM 23729237
ER
PT J
AU Werner, JM
Heller, T
Gordon, AM
Sheets, A
Sherker, AH
Kessler, E
Bean, KS
Stevens, M
Schmitt, J
Rehermann, B
AF Werner, Jens Martin
Heller, Theo
Gordon, Ann Marie
Sheets, Arlene
Sherker, Averell H.
Kessler, Ellen
Bean, Kathleen S.
Stevens, M'Lou
Schmitt, James
Rehermann, Barbara
TI Innate Immune Responses in Hepatitis C Virus-Exposed Healthcare Workers
Who Do Not Develop Acute Infection
SO HEPATOLOGY
LA English
DT Article
ID NATURAL-KILLER-CELLS; HUMAN DENDRITIC CELLS; NK CELLS; T-CELLS; B-VIRUS;
ACTIVATION; EXPRESSION; RECEPTORS; THERAPY; MANNER
AB Hepatitis C virus (HCV) infection typically results in chronic disease with HCV outpacing antiviral immune responses. Here we asked whether innate immune responses are induced in healthcare workers who are exposed to small amounts of HCV, but do not develop systemic infection and acute liver disease. Twelve healthcare workers with accidental percutaneous exposure to HCV-infected blood were prospectively studied for up to 6 months for phenotype and function of natural killer T (NKT) and NK cells, kinetics of serum chemokines, and vigor and specificity of HCV-specific T-cell responses. Eleven healthcare workers tested negative for HCV RNA and HCV antibodies. All but one of these aviremic cases displayed NKT cell activation, increased serum chemokines levels, and NK cell responses with increased CD122, NKp44, NKp46, and NKG2A expression, cytotoxicity (as determined by TRAIL and CD107a expression), and interferon-gamma (IFN-) production. This multifunctional NK cell response appeared a month earlier than in the one healthcare worker who developed high-level viremia, and it differed from the impaired IFN- production, which is typical for NK cells in chronic HCV infection. The magnitude of NKT cell activation and NK cell cytotoxicity correlated with the magnitude of the subsequent HCV-specific T-cell response. T-cell responses targeted nonstructural HCV sequences that require translation of viral RNA, which suggests that transient or locally contained HCV replication occurred without detectable systemic viremia. Conclusion: Exposure to small amounts of HCV induces innate immune responses, which correlate with the subsequent HCV-specific T-cell response and may contribute to antiviral immunity. (Hepatology 2013;58:1621-1631)
C1 [Werner, Jens Martin; Heller, Theo; Rehermann, Barbara] NIDDK, Liver Dis Branch, NIH, DHHS, Bethesda, MD 20892 USA.
[Gordon, Ann Marie; Sheets, Arlene] Medstar Washington Hosp Ctr, Washington, DC USA.
[Sherker, Averell H.] Washington Hosp Ctr, Ctr Liver Dis, Washington, DC 20010 USA.
[Kessler, Ellen; Bean, Kathleen S.] Inova Fairfax Hosp, Falls Church, VA USA.
[Stevens, M'Lou; Schmitt, James] NIH, Occupat Med Serv, Bethesda, MD 20892 USA.
RP Rehermann, B (reprint author), NIDDK, Immunol Sect, Liver Dis Branch, NIH,DHHS, 10 Ctr Dr,Bldg 10,Rm 9B16, Bethesda, MD 20892 USA.
EM Rehermann@nih.gov
OI Werner, Jens/0000-0001-7156-4370
FU Deutsche Forschungsgemeinschaft, Bonn, Germany [We- 4675/1-1]; NIDDK NIH
intramural research program
FX Supported by grant We- 4675/1-1 from the Deutsche
Forschungsgemeinschaft, Bonn, Germany (to J.M.W.) and by the NIDDK NIH
intramural research program.
NR 33
TC 26
Z9 27
U1 0
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0270-9139
EI 1527-3350
J9 HEPATOLOGY
JI Hepatology
PD NOV
PY 2013
VL 58
IS 5
BP 1621
EP 1631
DI 10.1002/hep.26353
PG 11
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 243OZ
UT WOS:000326327600013
PM 23463364
ER
PT J
AU Noureddin, M
Yates, KP
Vaughn, IA
Neuschwander-Tetri, BA
Sanyal, AJ
McCullough, A
Merriman, R
Hameed, B
Doo, E
Kleiner, DE
Behling, C
Loomba, R
AF Noureddin, Mazen
Yates, Katherine P.
Vaughn, Ivana A.
Neuschwander-Tetri, Brent A.
Sanyal, Arun J.
McCullough, Arthur
Merriman, Raphael
Hameed, Bilal
Doo, Edward
Kleiner, David E.
Behling, Cynthia
Loomba, Rohit
CA NASH CRN
TI Clinical and Histological Determinants of Nonalcoholic Steatohepatitis
and Advanced Fibrosis in Elderly Patients
SO HEPATOLOGY
LA English
DT Article
ID FATTY LIVER-DISEASE; NATURAL-HISTORY; UNITED-STATES; HEPATIC STEATOSIS;
CONTROLLED-TRIAL; SCORING SYSTEM; VITAMIN-E; POPULATION; PREVALENCE;
NAFLD
AB The characteristics of nonalcoholic fatty liver disease (NAFLD) in elderly patients are unknown. Therefore, we aimed to examine the differences between elderly and nonelderly patients with NAFLD and to identify determinants of nonalcoholic steatohepatitis (NASH) and advanced fibrosis (bridging fibrosis or cirrhosis) in elderly patients. This is a cross-sectional analysis of adult participants who were prospectively enrolled in the NASH Clinical Research Network studies. Participants were included based on availability of the centrally reviewed liver histology data within 1 year of enrollment, resulting in 61 elderly (age 65 years) and 735 nonelderly (18-64 years) participants. The main outcomes were the presence of NASH and advanced fibrosis. Compared to nonelderly patients with NAFLD, elderly patients had a higher prevalence of NASH (56% versus 72%, P=0.02), and advanced fibrosis (25% versus 44%, P=0.002). Compared to nonelderly patients with NASH, elderly patients with NASH had higher rates of advanced fibrosis (35% versus 52%, P=0.03), as well as other features of severe liver disease including the presence of ballooning degeneration, acidophil bodies, megamitochondria, and Mallory-Denk bodies (P0.05 for each). In multiple logistic regression analyses, independent determinants of NASH in elderly patients included higher aspartate aminotransferase (AST) (odds ratio [OR]=1.12, P=0.007) and lower platelets (OR=0.98, P=0.02); and independent determinants of advanced fibrosis included higher AST (OR=1.08, P=0.007), lower alanine aminotransferase value (OR=0.91, P=0.002), and an increased odds of having low high-density lipoprotein (OR=8.35, P=0.02). Conclusion: Elderly patients are more likely to have NASH and advanced fibrosis than nonelderly patients with NAFLD. Liver biopsy may be considered in elderly patients and treatment should be initiated in those with NASH and advanced fibrosis. (HEPATOLOGY 2013;58:1644-1654)
C1 [Noureddin, Mazen; Loomba, Rohit] Univ Calif San Diego, Sch Med, Div Gastroenterol & Epidemiol, La Jolla, CA 92093 USA.
[Yates, Katherine P.; Vaughn, Ivana A.] Johns Hopkins Univ, Data Coordinating Ctr, Baltimore, MD USA.
[Neuschwander-Tetri, Brent A.] St Louis Univ, Div Gastroenterol, 6, St Louis, MO 63103 USA.
[Sanyal, Arun J.] Virginia Commonwealth Univ, Dept Internal Med, Div Internal Med, Div Gastroenterol, Richmond, VA USA.
[McCullough, Arthur] Cleveland Clin Fdn, Metro Hlth Clin Ctr, Case Western Reserve Sch Med, Dept Gastroenterol Hepatol, Cleveland, OH 44195 USA.
[Merriman, Raphael; Hameed, Bilal] Univ Calif San Francisco, Div Gastroenterol, San Francisco, CA 94143 USA.
[Doo, Edward] NIDDK, Bethesda, MD 20892 USA.
[Kleiner, David E.] NCI, Pathol Lab, Bethesda, MD 20892 USA.
[Behling, Cynthia] Univ Calif San Diego, Dept Pathol, Sharp Mem Hosp, San Diego, CA 92103 USA.
RP Loomba, R (reprint author), Univ Calif San Diego, Sch Med, Div Gastroenterol & Epidemiol, UC 303,MC 0063,9500 Gilman Dr, La Jolla, CA 92093 USA.
EM roloomba@ucsd.edu
RI Vaughn, Ivana/B-6138-2016;
OI Vaughn, Ivana/0000-0002-7201-0289; Kleiner, David/0000-0003-3442-4453
FU NIDDK, NIH
FX The study was sponsored by the NIDDK, NIH. As per the policy of the
network, the article was reviewed by the NIDDK prior to publication. The
authors take full responsibility for the data analyses and credibility
of findings.
NR 51
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Z9 36
U1 0
U2 7
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 2013
VL 58
IS 5
BP 1644
EP 1654
DI 10.1002/hep.26465
PG 11
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 243OZ
UT WOS:000326327600015
PM 23686698
ER
PT J
AU Morales-Ibanez, O
Dominguez, M
Ki, SH
Marcos, M
Chaves, JF
Nguyen-Khac, E
Houchi, H
Affo, S
Sancho-Bru, P
Altamirano, J
Michelena, J
Garcia-Pagan, JC
Abraldes, JG
Arroyo, V
Caballeria, J
Laso, FJ
Gao, B
Bataller, R
AF Morales-Ibanez, Oriol
Dominguez, Marlene
Ki, Sung H.
Marcos, Miguel
Chaves, Javier F.
Nguyen-Khac, Eric
Houchi, Hakim
Affo, Silvia
Sancho-Bru, Pau
Altamirano, Jose
Michelena, Javier
Garcia-Pagan, Juan Carlos
Abraldes, Juan G.
Arroyo, Vicente
Caballeria, Juan
Laso, Francisco-Javier
Gao, Bin
Bataller, Ramon
TI Human and Experimental Evidence Supporting a Role for Osteopontin in
Alcoholic Hepatitis
SO HEPATOLOGY
LA English
DT Article
ID LIVER-DISEASE PATHOGENESIS; INDUCED INFLAMMATION; GENE-EXPRESSION;
SCORING SYSTEM; MURINE MODEL; FIBROSIS; STRESS; POLYMORPHISMS; HEDGEHOG;
TARGETS
AB We identified, in the transcriptome analysis of patients with alcoholic hepatitis (AH), osteopontin (OPN) as one of the most up-regulated genes. Here, we used a translational approach to investigate its pathogenic role. OPN hepatic gene expression was quantified in patients with AH and other liver diseases. OPN protein expression and processing were assessed by immmunohistochemistry, western blotting and enzyme-linked immunosorbent assay. OPN gene polymorphisms were evaluated in patients with alcoholic liver disease. The role of OPN was evaluated in OPN-/- mice with alcohol-induced liver injury. OPN biological actions were studied in human hepatic stellate cells (HSCs) and in precision-cut liver slices. Hepatic expression and serum levels of OPN were markedly increased in AH, compared to normal livers and other types of chronic liver diseases, and correlated with short-term survival. Serum levels of OPN also correlated with hepatic expression and disease severity. OPN was mainly expressed in areas with inflammation and fibrosis. Two proteases that process OPN (thrombin and matrix metalloproteinase 7) and cleaved OPN were increased in livers with AH. Patients with AH had a tendency of a lower frequency of the CC genotype of the +1239C single-nucleotide polymorphism of the OPN gene, compared to patients with alcohol abuse without liver disease. Importantly, OPN-/- mice were protected against alcohol-induced liver injury and showed decreased expression of inflammatory cytokines. Finally, OPN was induced by lipopolysaccharide and stimulated inflammatory actions in HSCs. Conclusion: Human and experimental data suggest a role for OPN in the pathogenesis of AH. Further studies should evaluate OPN as a potential therapeutic target. (Hepatology 2013;58:1742-1756)
C1 [Morales-Ibanez, Oriol; Dominguez, Marlene; Affo, Silvia; Sancho-Bru, Pau; Altamirano, Jose; Michelena, Javier; Garcia-Pagan, Juan Carlos; Abraldes, Juan G.; Arroyo, Vicente; Caballeria, Juan; Bataller, Ramon] Hosp Clin Barcelona, CIBER Enfermedades Hepaticas Digest CIBERehd, Inst Invest Biomed August Pi & Sunyer IDIBAPS, Liver Unit, Barcelona, Spain.
[Ki, Sung H.; Gao, Bin] Natl Inst Hlth, Natl Inst Alcohol Abuse & Alcoholism, Lab Liver Dis, Bethesda, MD USA.
[Marcos, Miguel; Laso, Francisco-Javier] IBSAL Univ, Hosp Salamanca, Dept Internal Med, Alcoholism Unit, Salamanca, Spain.
[Chaves, Javier F.] Res Fdn Hosp Clin, Genotyping & Genet Diag Unit, Valencia, Spain.
[Nguyen-Khac, Eric; Houchi, Hakim] Univ Picardie, Amiens Univ Hosp, INSERM, Serv Hepatogastroenterol,GRAP,ERI 24, Amiens, France.
[Bataller, Ramon] Univ N Carolina, Dept Med, Div Gastroenterol & Hepatol, Chapel Hill, NC 27599 USA.
[Bataller, Ramon] Univ N Carolina, Dept Nutr, Div Gastroenterol & Hepatol, Chapel Hill, NC 27599 USA.
RP Bataller, R (reprint author), Univ N Carolina, Dept Med, Div Gastroenterol & Hepatol, 2209 McGavran Greensberg, Chapel Hill, NC 27599 USA.
EM ramon_bataller@med.unc.edu
RI Sancho-Bru, Pau/D-4900-2014; Arroyo, Vicente/F-9189-2015; Marcos,
Miguel/B-3550-2008; Garcia-Pagan, Juan Carlos/P-6291-2015;
OI Sancho-Bru, Pau/0000-0001-5569-9259; Arroyo,
Vicente/0000-0002-2728-1848; Marcos, Miguel/0000-0003-1269-4487;
Garcia-Pagan, Juan Carlos/0000-0001-9032-4954; CHAVES, FELIPE
J/0000-0001-8009-3689; Affo, Silvia/0000-0002-9731-3913
FU Instituto de Salud Carlos III [FIS PI080237, FIS PS09/01164]; IDI-BAPS;
Instituto Carlos III, Miguel Servet [CP11/00071]; European Commission;
European Cosmetics Association (COLIPA) [HeMiBio-HEALTH-F5-2010-266777];
Fundacion Banco Bilbao Vizcaya Argentaria
FX This work was supported by grants from the Instituto de Salud Carlos III
(FIS PI080237 and FIS PS09/01164; to R. B. and J.C., respectively). S.
A. received a grant from IDI-BAPS. P.S.-B. received grants from
Instituto Carlos III, Miguel Servet (CP11/00071), and from the European
Commission (within its FP7 Cooperation Program) and the European
Cosmetics Association (COLIPA; o HeMiBio-HEALTH-F5-2010-266777). J.A.
received a grant from Fundacion Banco Bilbao Vizcaya Argentaria.
NR 29
TC 39
Z9 39
U1 3
U2 14
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 2013
VL 58
IS 5
BP 1742
EP 1756
DI 10.1002/hep.26521
PG 15
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 243OZ
UT WOS:000326327600024
PM 23729174
ER
PT J
AU Bertola, A
Park, O
Gao, B
AF Bertola, Adeline
Park, Ogyi
Gao, Bin
TI Chronic Plus Binge Ethanol Feeding Synergistically Induces Neutrophil
Infiltration and Liver Injury in Mice: A Critical Role for E-selectin
SO HEPATOLOGY
LA English
DT Article
ID SEVERE ALCOHOLIC HEPATITIS; A-INDUCED HEPATITIS; LEUKOCYTE RECRUITMENT;
ADHESION MOLECULES; ENDOTHELIAL-CELLS; GROWTH-FACTOR; DISEASE;
EXPRESSION; PATHOGENESIS; INFLAMMATION
AB Chronic plus binge ethanol feeding acts synergistically to induce liver injury in mice, but the mechanisms underlying this phenomenon remain unclear. Here, we show that chronic plus binge ethanol feeding synergistically up-regulated the hepatic expression of interleukin-1 and tumor necrosis factor alpha and induced neutrophil accumulation in the liver, compared with chronic or binge feeding alone. In vivo depletion of neutrophils through administration of an anti-Ly6G antibody markedly reduced chronic-binge ethanol feeding-induced liver injury. Real-time polymerase chain reaction analyses revealed that hepatic E-selectin expression was up-regulated 10-fold, whereas expression of other neutrophil infiltration-related adhesion molecules (e.g., P-selectin, intercellular adhesion molecule 1, and vascular cell adhesion molecule 1) was slightly up- or down-regulated in this chronic-binge model. The genetic deletion of E-selectin prevented chronic-binge ethanol-induced hepatic neutrophil infiltration as well as elevation of serum transaminases without affecting ethanol-induced steatosis. In addition, E-selectin-deficient mice showed reduced hepatic expression of several proinflammatory cytokines, chemokines, and adhesion molecules, compared to wild-type mice, after chronic-binge ethanol feeding. Finally, the expression of E-selectin was highly up-regulated in human alcoholic fatty livers, but not in alcoholic cirrhosis. Conclusions: Chronic-binge ethanol feeding up-regulates expression of proinflammatory cytokines, followed by the induction of E-selectin. Elevated E-selectin plays an important role in hepatic neutrophil infiltration and injury induced by chronic-binge feeding in mice and may also contribute to the pathogenesis of early stages of human alcoholic liver disease.
C1 [Bertola, Adeline; Park, Ogyi; Gao, Bin] NIAAA, Natl Inst Hlth, Lab Liver Dis, Bethesda, MD 20892 USA.
RP Gao, B (reprint author), NIAAA, Natl Inst Hlth, Lab Liver Dis, 5625 Fishers Lane, Bethesda, MD 20892 USA.
EM bgao@mail.nih.gov
OI Bertola, Adeline/0000-0002-4885-8423
FU National Institute on Alcohol Abuse and Alcoholism/National Institutes
of Health
FX This work was supported by the intramural program of the National
Institute on Alcohol Abuse and Alcoholism/National Institutes of Health.
NR 39
TC 16
Z9 17
U1 1
U2 6
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 2013
VL 58
IS 5
BP 1814
EP 1823
DI 10.1002/hep.26419
PG 10
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 243OZ
UT WOS:000326327600030
ER
PT J
AU Mukherjee, G
Geliebter, A
Babad, J
Santamaria, P
Serreze, DV
Freeman, GJ
Tarbell, KV
Sharpe, A
DiLorenzo, TP
AF Mukherjee, Gayatri
Geliebter, Ari
Babad, Jeffrey
Santamaria, Pere
Serreze, David V.
Freeman, Gordon J.
Tarbell, Kristin V.
Sharpe, Arlene
DiLorenzo, Teresa P.
TI DEC-205-mediated antigen targeting to steady-state dendritic cells
induces deletion of diabetogenic CD8 T cells independently of PD-1 and
PD-L1
SO INTERNATIONAL IMMUNOLOGY
LA English
DT Article
DE Autoimmunity; diabetes; NOD mice
ID NONOBESE DIABETIC MICE; IN-VIVO; NOD MICE; MONOCLONAL-ANTIBODY; RECEPTOR
DEC-205; ISLET ANTIGENS; EXPRESSION; TOLERANCE; RESPONSES; SUBSETS
AB Targeting antigen to steady state DCs causes deletion of endogenous islet-specific T cells.CD8 T cells specific for islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP) have been implicated in type 1 diabetes in both humans and non-obese diabetic (NOD) mice, in which T cells specific for IGRP(206214) are highly prevalent. We sought to manipulate these pathogenic T cells by exploiting the ability of steady-state dendritic cells (DCs) to present antigens in a tolerogenic manner. The endocytic receptor DEC-205 was utilized to deliver an IGRP(206214) mimotope to DCs in NOD mice, and the impact of this delivery on a polyclonal population of endogenous islet-reactive cognate T cells was determined. Assessment of islet-infiltrating CD8 T cells showed a decrease in the percentage, and the absolute number, of endogenous IGRP(206214)-specific T cells when the mimotope was delivered to DCs, compared with delivery of a specificity control. Employing an adoptive transfer system, deletion of CD8 T cells as a result of DEC-205-mediated antigen targeting was found to occur independently of programmed death-1 (PD-1) and its ligand (PD-L1), both often implicated in the regulation of peripheral T-cell tolerance. Given its promise for the manipulation of self-reactive polyclonal T cells demonstrated here, the distinctive characteristics of this antigen delivery system will be important to appreciate as its potential as an intervention for autoimmune diseases continues to be investigated.
C1 [Mukherjee, Gayatri; Geliebter, Ari; Babad, Jeffrey; DiLorenzo, Teresa P.] Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10461 USA.
[Santamaria, Pere] Univ Calgary, Julia McFarlane Diabet Res Ctr, Calgary, AB T2N 4N1, Canada.
[Santamaria, Pere] Univ Calgary, Fac Med, Dept Microbiol Immunol & Infect Dis, Calgary, AB T2N 4N1, Canada.
[Santamaria, Pere] Inst Invest Biomed August Pi & Sunyer, Barcelona 08036, Spain.
[Serreze, David V.] Jackson Lab, Bar Harbor, ME 04609 USA.
[Freeman, Gordon J.] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA.
[Freeman, Gordon J.] Harvard Univ, Sch Med, Dept Med, Boston, MA 02215 USA.
[Tarbell, Kristin V.] Natl Inst Diabet & Digest & Kidney Dis, NIH, Diabet Endocrinol & Obes Branch, Immune Tolerance Sect, Bethesda, MD 20892 USA.
[Sharpe, Arlene] Harvard Univ, Sch Med, Dept Microbiol & Immunol, Boston, MA 02215 USA.
[Sharpe, Arlene] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02215 USA.
[DiLorenzo, Teresa P.] Albert Einstein Coll Med, Dept Med, Div Endocrinol, Bronx, NY 10461 USA.
RP DiLorenzo, TP (reprint author), Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10461 USA.
EM teresa.dilorenzo@einstein.yu.edu
OI Tarbell, Kristin/0000-0003-3738-379X
FU National Institutes of Health [R01 DK094327, R01 DK064315, R01 DK046266,
U01 DK072473, P01 AI056299, P60 DK020541]; Juvenile Diabetes Research
Foundation; American Diabetes Association; Irma T. Hirschl/Monique
Weill-Caulier Trust; Intramural Research Program of the National
Institute of Diabetes and Digestive and Kidney Diseases; Canadian
Institutes of Health Research; Canadian Diabetes Association; National
Institutes of Health Cancer Center [P30 CA013330]
FX National Institutes of Health [R01 DK094327 and R01 DK064315 to T.P.D.,
R01 DK046266 and U01 DK072473 (Beta Cell Biology Consortium) to D.V.S.,
P01 AI056299 to A.S., P60 DK020541 (Albert Einstein College of
Medicine's Diabetes Research Center)]; the Juvenile Diabetes Research
Foundation to D. V. S. and T. P. D.; the American Diabetes Association
to D. V. S. and T. P. D.; the Irma T. Hirschl/Monique Weill-Caulier
Trust to T. P. D.; Intramural Research Program of the National Institute
of Diabetes and Digestive and Kidney Diseases to K. V. T.; Canadian
Institutes of Health Research to P. S.; Canadian Diabetes Association to
Julia McFarlane Diabetes Research Centre; National Institutes of Health
Cancer Center (P30 CA013330 for flow cytometry facility at Albert
Einstein College of Medicine). P.S. is scientific founder of Parvus
Therapeutics, Inc. and a scientist of Alberta Innovates-Health
Solutions. T.P.D. is the Diane Belfer, Cypres & Endelson Families
Faculty Scholar in Diabetes Research.
NR 49
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Z9 7
U1 0
U2 8
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0953-8178
EI 1460-2377
J9 INT IMMUNOL
JI Int. Immunol.
PD NOV
PY 2013
VL 25
IS 11
BP 651
EP 660
DI 10.1093/intimm/dxt031
PG 10
WC Immunology
SC Immunology
GA 244GR
UT WOS:000326375900005
PM 24021877
ER
PT J
AU Xu, H
Lasso, A
Guion, P
Krieger, A
Kaushal, A
Singh, AK
Pinto, PA
Coleman, J
Grubb, RL
Lattouf, JB
Menard, C
Whitcomb, LL
Fichtinger, G
AF Xu, Helen
Lasso, Andras
Guion, Peter
Krieger, Axel
Kaushal, Aradhana
Singh, Anurag K.
Pinto, Peter A.
Coleman, Jonathan
Grubb, Robert L., III
Lattouf, Jean-Baptiste
Menard, Cynthia
Whitcomb, Louis L.
Fichtinger, Gabor
TI Accuracy analysis in MRI-guided robotic prostate biopsy
SO INTERNATIONAL JOURNAL OF COMPUTER ASSISTED RADIOLOGY AND SURGERY
LA English
DT Article
DE Prostate biopsy; Accuracy validation; MRI-guidance; Image registration
ID CANCER; REGISTRATION; BRACHYTHERAPY; INTERVENTIONS; DESIGN
AB To assess retrospectively the clinical accuracy of an magnetic resonance imaging-guided robotic prostate biopsy system that has been used in the US National Cancer Institute for over 6 years.
Series of 2D transverse volumetric MR image slices of the prostate both pre (high-resolution T2-weighted)- and post (low-resolution)- needle insertions were used to evaluate biopsy accuracy. A three-stage registration algorithm consisting of an initial two-step rigid registration followed by a B-spline deformable alignment was developed to capture prostate motion during biopsy. The target displacement (distance between planned and actual biopsy target), needle placement error (distance from planned biopsy target to needle trajectory), and biopsy error (distance from actual biopsy target to needle trajectory) were calculated as accuracy assessment.
A total of 90 biopsies from 24 patients were studied. The registrations were validated by checking prostate contour alignment using image overlay, and the results were accurate to within 2 mm. The mean target displacement, needle placement error, and clinical biopsy error were 5.2, 2.5, and 4.3 mm, respectively.
The biopsy error reported suggests that quantitative imaging techniques for prostate registration and motion compensation may improve prostate biopsy targeting accuracy.
C1 [Xu, Helen; Lasso, Andras; Fichtinger, Gabor] Queens Univ, Kingston, ON, Canada.
[Guion, Peter; Kaushal, Aradhana; Pinto, Peter A.] NIH, Bethesda, MD 20892 USA.
[Krieger, Axel] Childrens Natl Med Ctr, Washington, DC 20010 USA.
[Singh, Anurag K.] Rosewell Pk Canc Inst, Buffalo, NY USA.
[Coleman, Jonathan] Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA.
[Grubb, Robert L., III] Washington Univ, St Louis, MO USA.
[Lattouf, Jean-Baptiste] Ctr Hosp Univ Montreal, Montreal, PQ, Canada.
[Menard, Cynthia] Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada.
[Whitcomb, Louis L.; Fichtinger, Gabor] Johns Hopkins Univ, Baltimore, MD USA.
RP Xu, H (reprint author), Queens Univ, Kingston, ON, Canada.
EM helen@cs.queensu.ca
OI Coleman, Jonathan/0000-0002-6428-7835
FU US National Institutes of Health (NIH) [5R01CA111288-04,
5R01EB002963-05]; Canadian Ontario Graduate Scholarship (OGS); Applied
Cancer Research Unit program of Cancer Care Ontario; Ontario Ministry of
Health and Long-Term Care; Cancer Ontario Research Chair
FX This work is supported by: US National Institutes of Health (NIH)
5R01CA111288-04 and 5R01EB002963-05, Canadian Ontario Graduate
Scholarship (OGS), and Applied Cancer Research Unit program of Cancer
Care Ontario with funds provided by the Ontario Ministry of Health and
Long-Term Care. Gabor Fichtinger was funded as a Cancer Ontario Research
Chair.
NR 26
TC 6
Z9 6
U1 2
U2 5
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 1861-6410
EI 1861-6429
J9 INT J COMPUT ASS RAD
JI Int. J. Comput. Assist. Radiol. Surg.
PD NOV
PY 2013
VL 8
IS 6
BP 937
EP 944
DI 10.1007/s11548-013-0831-9
PG 8
WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging;
Surgery
SC Engineering; Radiology, Nuclear Medicine & Medical Imaging; Surgery
GA 245HZ
UT WOS:000326455900007
PM 23532560
ER
PT J
AU Glasofer, DR
Haaga, DAF
Hannallah, L
Field, SE
Kozlosky, M
Reynolds, J
Yanovski, JA
Tanofsky-Kraff, M
AF Glasofer, Deborah R.
Haaga, David A. F.
Hannallah, Louise
Field, Sara E.
Kozlosky, Merel
Reynolds, James
Yanovski, Jack A.
Tanofsky-Kraff, Marian
TI Self-Efficacy Beliefs and Eating Behavior in Adolescent Girls At-Risk
for Excess Weight Gain and Binge Eating Disorder
SO INTERNATIONAL JOURNAL OF EATING DISORDERS
LA English
DT Article
DE self-efficacy; loss of control; adolescents; toxic food environment;
binge eating disorder; obesity
ID OVERWEIGHT CHILDREN; ADVERSE OUTCOMES; ADULT OBESITY; ENERGY-INTAKE;
BODY-FAT; YOUTH; PSYCHOPATHOLOGY; AVAILABILITY; ASSOCIATIONS; PREVALENCE
AB ObjectiveTo examine the relationship between self-related agency beliefs and observed eating behavior in adolescent girls with loss of control (LOC) eating.
MethodOne-hundred eleven adolescent girls (14.51.7 years; BMI: 27.12.6 kg/m(2)) were administered the General Self-Efficacy Scale and the Weight Efficacy Lifestyle Questionnaire (WEL). Adolescents then participated in a laboratory test meal.
ResultsGreater general and eating self-efficacy were associated with fewer episodes of LOC eating. General self-efficacy was inversely related to total intake at the meal (p<.01). Only the WEL availability subscale score, but not the other WEL subscales, was inversely related to total energy, snack, and dessert intake (ps<0.05).
DiscussionGeneral self-related agency beliefs may be important in relation to energy consumption. Among girls susceptible to disordered eating and obesity, the domain-specific belief in one's ability to refrain from eating when food is widely available may be especially salient in determining overeating in the current food environment. Further research is therefore needed to assess the predictive validity of these beliefs on eating and weight outcomes. (c) 2013 Wiley Periodicals, Inc. (Int J Eat Disord 2013; 46:663-668)
C1 [Glasofer, Deborah R.] New York State Psychiat Inst & Hosp, Div Clin Therapeut, New York, NY 10032 USA.
[Glasofer, Deborah R.] Columbia Univ, Dept Psychiat, Coll Phys & Surg, New York, NY USA.
[Haaga, David A. F.] Amer Univ, Dept Psychol, Washington, DC 20016 USA.
[Hannallah, Louise; Field, Sara E.; Tanofsky-Kraff, Marian] Uniformed Serv Univ Hlth Sci, Dept Med & Clin Psychol, Bethesda, MD 20814 USA.
[Hannallah, Louise; Field, Sara E.; Yanovski, Jack A.; Tanofsky-Kraff, Marian] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Growth & Obes, Program Dev Endocrinol & Genet, NIH, Bethesda, MD USA.
[Kozlosky, Merel] NIH, Dept Nutr, Ctr Clin, DHHS, Bethesda, MD 20892 USA.
[Reynolds, James] NIH, Dept Nucl Med, Hatfield Clin Res Ctr, DHHS, Bethesda, MD USA.
RP Tanofsky-Kraff, M (reprint author), Uniformed Serv Univ Hlth Sci, Dept Med & Clin Psychol, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA.
EM marian.tanofsky-kraff@usuhs.edu
OI Yanovski, Jack/0000-0001-8542-1637
FU Intramural NIH HHS [Z99 HD999999, ZIA HD000641-18]; NIDDK NIH HHS [R01
DK080906]
NR 48
TC 9
Z9 9
U1 1
U2 11
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0276-3478
EI 1098-108X
J9 INT J EAT DISORDER
JI Int. J. Eating Disord.
PD NOV
PY 2013
VL 46
IS 7
BP 663
EP 668
DI 10.1002/eat.22160
PG 6
WC Psychology, Clinical; Nutrition & Dietetics; Psychiatry; Psychology
SC Psychology; Nutrition & Dietetics; Psychiatry
GA 241OG
UT WOS:000326175900003
PM 23881587
ER
PT J
AU Oakley, RH
Cidlowski, JA
AF Oakley, Robert H.
Cidlowski, John A.
TI The biology of the glucocorticoid receptor: New signaling mechanisms in
health and disease
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Article
DE Glucocorticoid receptor; glucocorticoid; isoforms; glucocorticoid
signaling
ID TRABECULAR MESHWORK CELLS; NF-KAPPA-B; GENE-EXPRESSION PROFILES;
ACTIVATED PROTEIN-KINASE; PRE-MESSENGER-RNA; BETA-ISOFORM;
TRANSCRIPTIONAL ACTIVITY; TRANSLATIONAL ISOFORMS; DNA-BINDING;
ANTIINFLAMMATORY ACTIONS
AB Glucocorticoids are primary stress hormones necessary for life that regulate numerous physiologic processes in an effort to maintain homeostasis. Synthetic derivatives of these hormones have been mainstays in the clinic for treating inflammatory diseases, autoimmune disorders, and hematologic cancers. The physiologic and pharmacologic actions of glucocorticoids are mediated by the glucocorticoid receptor (GR), a member of the nuclear receptor superfamily of ligand-dependent transcription factors. Ligand-occupied GR induces or represses the transcription of thousands of genes through direct binding to DNA response elements, physically associating with other transcription factors, or both. The traditional view that glucocorticoids act through a single GR protein has changed dramatically with the discovery of a large cohort of receptor isoforms with unique expression, gene-regulatory, and functional profiles. These GR subtypes are derived from a single gene by means of alternative splicing and alternative translation initiation mechanisms. Posttranslational modification of these GR isoforms further expands the diversity of glucocorticoid responses. Here we discuss the origin and molecular properties of the GR isoforms and their contribution to the specificity and sensitivity of glucocorticoid signaling in healthy and diseased tissues.
C1 [Oakley, Robert H.; Cidlowski, John A.] NIEHS, Lab Signal Transduct, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
RP Cidlowski, JA (reprint author), NIEHS, POB 12233,MD F3-07, Res Triangle Pk, NC 27709 USA.
EM cidlows1@niehs.nih.gov
FU National Institutes of Health/National Institute of Environmental Health
Sciences
FX Supported by the Intramural Research Program of the National Institutes
of Health/National Institute of Environmental Health Sciences.
NR 128
TC 101
Z9 106
U1 3
U2 46
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 2013
VL 132
IS 5
BP 1033
EP 1044
DI 10.1016/j.jaci.2013.09.007
PG 12
WC Allergy; Immunology
SC Allergy; Immunology
GA 242JH
UT WOS:000326235600002
PM 24084075
ER
PT J
AU Zhang, YE
Newfeld, SJ
AF Zhang, Ying E.
Newfeld, Stuart J.
TI Meeting report - TGF-beta superfamily: signaling in development and
disease
SO JOURNAL OF CELL SCIENCE
LA English
DT Article
ID GROWTH-FACTOR-BETA; RECEPTOR; METASTASIS
C1 [Zhang, Ying E.] NCI, Cellular & Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Newfeld, Stuart J.] Arizona State Univ, Sch Life Sci, Tempe, AZ 85287 USA.
RP Zhang, YE (reprint author), NCI, Cellular & Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM zhangyin@mail.nih.gov; newfeld@asu.edu
RI Zhang, Ying/G-3657-2015
OI Zhang, Ying/0000-0003-2753-7601
FU National Institutes of Health (National Cancer Institute Center for
Cancer Research); National Human Genome Research Institute, National
Institute of General Medical Sciences; National Institute of
Neurological Disorders and Stroke
FX Y.E.Z. is supported by the intramural research program of National
Institutes of Health (National Cancer Institute Center for Cancer
Research); S.J.N. is supported by the National Human Genome Research
Institute, National Institute of General Medical Sciences and the
National Institute of Neurological Disorders and Stroke.
NR 17
TC 0
Z9 0
U1 2
U2 5
PU COMPANY OF BIOLOGISTS LTD
PI CAMBRIDGE
PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL,
CAMBS, ENGLAND
SN 0021-9533
EI 1477-9137
J9 J CELL SCI
JI J. Cell Sci.
PD NOV 1
PY 2013
VL 126
IS 21
BP 4809
EP 4813
DI 10.1242/jcs.142398
PG 5
WC Cell Biology
SC Cell Biology
GA 244MH
UT WOS:000326392500001
PM 24172535
ER
PT J
AU Webster, BR
Scott, I
Han, K
Li, JH
Lu, ZP
Stevens, MV
Malide, D
Chen, Y
Samsel, L
Connelly, PS
Daniels, MP
Mccoy, JP
Combs, CA
Gucek, M
Sack, MN
AF Webster, Bradley R.
Scott, Iain
Han, Kim
Li, Jian H.
Lu, Zhongping
Stevens, Mark V.
Malide, Daniela
Chen, Yong
Samsel, Leigh
Connelly, Patricia S.
Daniels, Mathew P.
Mccoy, J. Philip, Jr.
Combs, Christian A.
Gucek, Marjan
Sack, Michael N.
TI Restricted mitochondrial protein acetylation initiates mitochondrial
autophagy
SO JOURNAL OF CELL SCIENCE
LA English
DT Article
DE GCN5L1; SIRT3; Mitochondrial autophagy; Acetylation; Parkin
ID OXIDATIVE DAMAGE; CELL-DEATH; SIRT3; DEACETYLASE; IDENTIFICATION;
SPERMIDINE; MECHANISM; MITOPHAGY; PROMOTES; MUTATION
AB Because nutrient-sensing nuclear and cytosolic acetylation mediates cellular autophagy, we investigated whether mitochondrial acetylation modulates mitochondrial autophagy (mitophagy). Knockdown of GCN5L1, a component of the mitochondrial acetyltransferase machinery, diminished mitochondrial protein acetylation and augmented mitochondrial enrichment of autophagy mediators. This program was disrupted by SIRT3 knockdown. Chronic GCN5L1 depletion increased mitochondrial turnover and reduced mitochondrial protein content and/or mass. In parallel, mitochondria showed blunted respiration and enhanced 'stress-resilience'. Genetic disruption of autophagy mediators Atg5 and p62 (also known as SQSTM1), as well as GCN5L1 reconstitution, abolished deacetylation-induced mitochondrial autophagy. Interestingly, this program is independent of the mitophagy E3-ligase Parkin (also known as PARK2). Taken together, these data suggest that deacetylation of mitochondrial proteins initiates mitochondrial autophagy in a canonical autophagy-mediator-dependent program and shows that modulation of this regulatory program has ameliorative mitochondrial homeostatic effects.
C1 [Webster, Bradley R.; Scott, Iain; Han, Kim; Li, Jian H.; Lu, Zhongping; Stevens, Mark V.; Sack, Michael N.] NHLBI, Ctr Mol Med, NIH, Bethesda, MD 20892 USA.
[Malide, Daniela; Combs, Christian A.] NHLBI, Light Microscopy Core, NIH, Bethesda, MD 20892 USA.
[Chen, Yong; Gucek, Marjan] NHLBI, Prote Core, NIH, Bethesda, MD 20892 USA.
[Samsel, Leigh; Mccoy, J. Philip, Jr.] NHLBI, Flow Cytometry Core, NIH, Bethesda, MD 20892 USA.
[Connelly, Patricia S.; Daniels, Mathew P.] NHLBI, Electron Microscopy Core, NIH, Bethesda, MD 20892 USA.
RP Sack, MN (reprint author), NHLBI, Ctr Mol Med, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM sackm@nhlbi.nih.gov
RI chen, yong/E-2432-2011
FU National Institute of Heart, Lung, and Blood Institute Division of
Intramural Research [HL006047-01]
FX This work was supported by the National Institute of Heart, Lung, and
Blood Institute Division of Intramural Research [grant number
HL006047-01 to M.N.S.]. Deposited in PMC for release after 12 months.
NR 24
TC 29
Z9 29
U1 0
U2 15
PU COMPANY OF BIOLOGISTS LTD
PI CAMBRIDGE
PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL,
CAMBS, ENGLAND
SN 0021-9533
EI 1477-9137
J9 J CELL SCI
JI J. Cell Sci.
PD NOV 1
PY 2013
VL 126
IS 21
BP 4843
EP 4849
DI 10.1242/jcs.131300
PG 7
WC Cell Biology
SC Cell Biology
GA 244MH
UT WOS:000326392500005
PM 24006259
ER
PT J
AU Richards, VP
Greig, TW
Fair, PA
McCulloch, SD
Politz, C
Natoli, A
Driscoll, CA
Hoelzel, AR
David, V
Bossart, GD
Lopez, JV
AF Richards, Vincent P.
Greig, Thomas W.
Fair, Patricia A.
McCulloch, Stephen D.
Politz, Christine
Natoli, Ada
Driscoll, Carlos A.
Hoelzel, A. Rus
David, Victor
Bossart, Gregory D.
Lopez, Jose V.
TI Patterns of Population Structure for Inshore Bottlenose Dolphins along
the Eastern United States
SO JOURNAL OF HEREDITY
LA English
DT Article
DE Indian River Lagoon; microsatellite; mtDNA; Tursiops truncatus
ID INDIAN-RIVER LAGOON; SEX-BIASED DISPERSAL; GULF-OF-MEXICO;
TURSIOPS-TRUNCATUS; GENETIC-STRUCTURE; MICROSATELLITE MARKERS; CETACEAN
POPULATIONS; WESTERN-AUSTRALIA; SOUTH-CAROLINA; SPECIES TREES
AB Globally distributed, the bottlenose dolphin (Tursiops truncatus) is found in a range of offshore and coastal habitats. Using 15 microsatellite loci and mtDNA control region sequences, we investigated patterns of genetic differentiation among putative populations along the eastern US shoreline (the Indian River Lagoon, Florida, and Charleston Harbor, South Carolina) (microsatellite analyses: n = 125, mtDNA analyses: n = 132). We further utilized the mtDNA to compare these populations with those from the Northwest Atlantic, Gulf of Mexico, and Caribbean. Results showed strong differentiation among inshore, alongshore, and offshore habitats (Phi(ST) = 0.744). In addition, Bayesian clustering analyses revealed the presence of 2 genetic clusters (populations) within the 250 km Indian River Lagoon. Habitat heterogeneity is likely an important force diversifying bottlenose dolphin populations through its influence on social behavior and foraging strategy. We propose that the spatial pattern of genetic variation within the lagoon reflects both its steep longitudinal transition of climate and also its historical discontinuity and recent connection as part of Intracoastal Waterway development. These findings have important management implications as they emphasize the role of habitat and the consequence of its modification in shaping bottlenose dolphin population structure and highlight the possibility of multiple management units existing in discrete inshore habitats along the entire eastern US shoreline.
C1 [Richards, Vincent P.] Cornell Univ, Dept Populat Med & Diagnost Sci, Coll Vet Med, Ithaca, NY 14853 USA.
[Greig, Thomas W.; Fair, Patricia A.] Florida Atlantic Univ, Marine Mammal Res & Conservat Program, Harbor Branch Oceanog Inst, Pierce, FL USA.
[McCulloch, Stephen D.; Politz, Christine; Driscoll, Carlos A.; Bossart, Gregory D.; Lopez, Jose V.] NOAA, Ctr Coastal Environm Hlth & Biomol Res, Charleston, SC USA.
[Natoli, Ada; Hoelzel, A. Rus] Univ Durham, Sch Biol & Biomed Sci, Durham, England.
[David, Victor] Natl Canc Inst, Basic Res Lab Genom Div, Frederick, MD USA.
[Bossart, Gregory D.] Georgia Aquarium, Nw Atlanta, GA USA.
[Lopez, Jose V.] Nova SE Univ, Oceanog Ctr, Dania, FL USA.
RP Richards, VP (reprint author), Cornell Univ, Dept Populat Med & Diagnost Sci, Coll Vet Med, Ithaca, NY 14853 USA.
EM vpr3@cornell.edu
OI Driscoll, Carlos/0000-0003-2392-505X
FU State of Florida's Protect Wild Dolphins Specialty License Plate Fund;
NOAA/Center for Coastal Environmental Health and Biomolecular Research
(CCEHBR); NOAA/NMFS Marine Mammal Health and Stranding Response Program;
Intramural Research Program of the National Institutes of Health,
National Cancer Institute
FX State of Florida's Protect Wild Dolphins Specialty License Plate Fund;
NOAA/Center for Coastal Environmental Health and Biomolecular Research
(CCEHBR); NOAA/NMFS Marine Mammal Health and Stranding Response Program;
Intramural Research Program of the National Institutes of Health,
National Cancer Institute.
NR 95
TC 6
Z9 6
U1 8
U2 45
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0022-1503
EI 1465-7333
J9 J HERED
JI J. Hered.
PD NOV-DEC
PY 2013
VL 104
IS 6
BP 765
EP 778
DI 10.1093/jhered/est070
PG 14
WC Evolutionary Biology; Genetics & Heredity
SC Evolutionary Biology; Genetics & Heredity
GA 239RL
UT WOS:000326043000003
PM 24129993
ER
PT J
AU Chun, TW
Fauci, AS
AF Chun, Tae-Wook
Fauci, Anthony S.
TI Viral Persistence in HIV Infection: Much Known, Much to Learn
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Editorial Material
DE HIV; antiretroviral therapy; viral reservoirs; 2-LTR HIV DNA;
intensification; eradication; plasma viremia
ID ACTIVE ANTIRETROVIRAL THERAPY; RALTEGRAVIR INTENSIFICATION; REPLICATION;
RESERVOIR; CURE; GUT; ERADICATION; SUPPRESSION; ACTIVATION; DYNAMICS
C1 [Chun, Tae-Wook; Fauci, Anthony S.] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA.
RP Chun, TW (reprint author), NIAID, Immunoregulat Lab, NIH, 9000 Rockville Pike,Bldg 10,Rm 6A32, Bethesda, MD 20892 USA.
EM twchun@nih.gov
NR 26
TC 3
Z9 3
U1 0
U2 10
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 2013
VL 208
IS 9
BP 1356
EP 1358
DI 10.1093/infdis/jit455
PG 3
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 244HD
UT WOS:000326377500002
PM 23975884
ER
PT J
AU Chun, TW
Justement, JS
Murray, D
Kim, CJ
Blazkova, J
Hallahan, CW
Benko, E
Costiniuk, CT
Kandel, G
Ostrowski, M
Kaul, R
Moir, S
Casazza, JP
Koup, RA
Kovacs, C
Fauci, AS
AF Chun, Tae-Wook
Justement, J. Shawn
Murray, Danielle
Kim, Connie J.
Blazkova, Jana
Hallahan, Claire W.
Benko, Erika
Costiniuk, Cecilia T.
Kandel, Gabor
Ostrowski, Mario
Kaul, Rupert
Moir, Susan
Casazza, Joseph P.
Koup, Richard A.
Kovacs, Colin
Fauci, Anthony S.
TI Effect of Antiretroviral Therapy on HIV Reservoirs in Elite Controllers
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
DE human immunodeficiency virus; viral reservoirs; antiretroviral therapy;
elite controllers
ID LOW-LEVEL VIREMIA; VIRUS; INTENSIFICATION; INDIVIDUALS; REPLICATION;
SUPPRESSORS; INFECTION
AB Elite controllers suppress human immunodeficiency virus (HIV) viremia to below the limit of detection in the absence of antiretroviral therapy (ART). However, precise frequencies of CD4(+) T cells carrying replication-competent HIV and/or the dynamics of the infectious viral reservoirs in response to initiation and discontinuation of ART in elite controllers are unknown. We show that the size of the pool of CD4(+) T cells harboring infectious HIV diminished significantly after initiation of ART and rebounded to baseline upon cessation of therapy. Our data provide compelling evidence that persistent viral replication occurs in untreated elite controllers even in the absence of detectable plasma viremia.
C1 [Chun, Tae-Wook; Justement, J. Shawn; Murray, Danielle; Blazkova, Jana; Hallahan, Claire W.; Moir, Susan; Casazza, Joseph P.; Koup, Richard A.; Fauci, Anthony S.] NIAID, NIH, Bethesda, MD 20892 USA.
[Kim, Connie J.; Ostrowski, Mario; Kaul, Rupert; Kovacs, Colin] Univ Toronto, Dept Med, Toronto, ON, Canada.
[Benko, Erika; Kovacs, Colin] Maple Leaf Med Clin, Toronto, ON, Canada.
[Costiniuk, Cecilia T.] Ottawa Hosp, Dept Med, Toronto, ON, Canada.
[Kandel, Gabor; Ostrowski, Mario] St Michaels Hosp, Toronto, ON M5B 1W8, Canada.
[Kandel, Gabor; Ostrowski, Mario] Li Ka Shing Knowledge Inst, Toronto, ON, Canada.
RP Chun, TW (reprint author), NIH, Bldg 10,Rm 6A32,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM twchun@nih.gov
FU Intramural Research Program of the National Institute of Allergy and
Infectious Diseases, National Institutes of Health
FX This work was supported the Intramural Research Program of the National
Institute of Allergy and Infectious Diseases, National Institutes of
Health.
NR 15
TC 25
Z9 25
U1 0
U2 9
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 2013
VL 208
IS 9
BP 1443
EP 1447
DI 10.1093/infdis/jit306
PG 5
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 244HD
UT WOS:000326377500014
PM 23847057
ER
PT J
AU Shobab, L
Pleyer, U
Johnsen, J
Metzner, S
James, ER
Torun, N
Fay, MP
Liesenfeld, O
Grigg, ME
AF Shobab, Leila
Pleyer, Uwe
Johnsen, Joerdis
Metzner, Sylvia
James, Erick R.
Torun, N.
Fay, Michael P.
Liesenfeld, Oliver
Grigg, Michael E.
TI Toxoplasma Serotype Is Associated With Development of Ocular
Toxoplasmosis
SO JOURNAL OF INFECTIOUS DISEASES
LA English
DT Article
DE Diagnosis; ocular inflammatory disease; serotype; toxoplasmosis; uveitis
ID CONGENITAL TOXOPLASMOSIS; HIGH PREVALENCE; GONDII STRAINS;
POPULATION-STRUCTURE; GLOBAL REASSESSMENT; MEMORIAL-LECTURE;
AQUEOUS-HUMOR; I STRAINS; PCR; VIRULENCE
AB Background. Worldwide, ocular toxoplasmosis (OT) is the principal cause of posterior uveitis, a severe, life-altering disease. A Toxoplasma gondii enzyme-linked immunoassay that detects strain-specific antibodies present in serum was used to correlate serotype with disease.
Methods. Toxoplasma serotypes in consecutive serum samples from German uveitis patients with OT were compared with non-OT seropositive patients with noninfectious autoimmune posterior uveitis. OT patients were tested for association of parasite serotype with age, gender, location, clinical onset, size, visual acuity, or number of lesions (mean follow-up, 3.8 years) to determine association with recurrences.
Results. A novel, nonreactive (NR) serotype was detected more frequently in serum samples of OT patients (50/114, 44%) than in non-OT patients (4/56, 7%) (odds ratio, 10.0; 95% confidence interval 3.4-40.8; P < .0001). Non-OT patients were predominantly infected with Type II strains (39/56; 70%), consistent with expected frequencies in Central Europe. Among OT patients, those with NR serotypes experienced more frequent recurrences (P = .037). Polymerase chain reaction detected parasite DNA in 8/60 OT aqueous humor specimens but failed to identify Type II strain alleles.
Conclusions. Toxoplasma NR and Type II serotypes predominate in German OT patients. The NR serotype is associated with OT recurrences, underscoring the value of screening for management of disease.
C1 [Shobab, Leila; Grigg, Michael E.] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
[Fay, Michael P.] NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 USA.
[Pleyer, Uwe; Johnsen, Joerdis; Metzner, Sylvia; Torun, N.] Charite Univ Med Berlin, Dept Ophthalmol, Berlin, Germany.
[Liesenfeld, Oliver] Charite Univ Med Berlin, Inst Microbiol & Hyg, Berlin, Germany.
[James, Erick R.; Grigg, Michael E.] Univ British Columbia, Dept Med, Vancouver, BC, Canada.
RP Grigg, ME (reprint author), 4 Ctr Dr, Bethesda, MD 20892 USA.
EM griggm@niaid.nih.gov
OI Fay, Michael P./0000-0002-8643-9625
FU Intramural Research Program of the National Institutes of Health (NIH);
National Institute of Allergy and Infectious Diseases (NIAID); ToxoNet,
a program of the German Bundesministerium fur Bildung und Forschung
(BMBF)
FX This work was supported by the Intramural Research Program of the
National Institutes of Health (NIH) and National Institute of Allergy
and Infectious Diseases (NIAID; M. E. G.). M. E. G. is a scholar of the
Canadian Institute for Advanced Research (CIFAR) Program for Integrated
Microbial Biodiversity. U. P., N. T., and O. L. were supported by
ToxoNet, a program of the German Bundesministerium fur Bildung und
Forschung (BMBF).
NR 43
TC 17
Z9 17
U1 0
U2 5
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0022-1899
EI 1537-6613
J9 J INFECT DIS
JI J. Infect. Dis.
PD NOV 1
PY 2013
VL 208
IS 9
BP 1520
EP 1528
DI 10.1093/infdis/jit313
PG 9
WC Immunology; Infectious Diseases; Microbiology
SC Immunology; Infectious Diseases; Microbiology
GA 244HD
UT WOS:000326377500024
PM 23878321
ER
PT J
AU Tanpaiboon, P
Venditti, CP
AF Tanpaiboon, Pranoot
Venditti, Charles P.
TI Noncompaction of the ventricular myocardium and hydrops fetalis in
cobalamin C disease
SO JOURNAL OF INHERITED METABOLIC DISEASE
LA English
DT Letter
C1 [Tanpaiboon, Pranoot] Childrens Natl Med Ctr, Div Genet & Metab, Washington, DC 20010 USA.
[Venditti, Charles P.] NHGRI, Organ Acid Res Sect, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA.
RP Venditti, CP (reprint author), NHGRI, Organ Acid Res Sect, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA.
EM venditti@mail.nih.gov
FU Intramural NIH HHS [ZIA HG200318-09]
NR 2
TC 0
Z9 0
U1 0
U2 1
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0141-8955
EI 1573-2665
J9 J INHERIT METAB DIS
JI J. Inherit. Metab. Dis.
PD NOV
PY 2013
VL 36
IS 6
BP 1085
EP 1085
DI 10.1007/s10545-013-9644-9
PG 1
WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research &
Experimental
SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental
Medicine
GA 244GQ
UT WOS:000326375800023
PM 23974651
ER
PT J
AU Stefl, S
Nishi, H
Petukh, M
Panchenko, AR
Alexov, E
AF Stefl, Shannon
Nishi, Hafumi
Petukh, Marharyta
Panchenko, Anna R.
Alexov, Emil
TI Molecular Mechanisms of Disease-Causing Missense Mutations
SO JOURNAL OF MOLECULAR BIOLOGY
LA English
DT Review
ID SINGLE-NUCLEOTIDE POLYMORPHISMS; PROTEIN INTRINSIC DISORDER; AMINO-ACID
SUBSTITUTIONS; SUPPORT VECTOR MACHINES; HYDROGEN-BOND NETWORK;
FREE-ENERGY CHANGES; STABILITY CHANGES; SUBCELLULAR-LOCALIZATION;
FUNCTIONAL SITES; RARE VARIANTS
AB Genetic variations resulting in a change of amino acid sequence can have a dramatic effect on stability, hydrogen bond network, conformational dynamics, activity and many other physiologically important properties of proteins. The substitutions of only one residue in a protein sequence, so-called missense mutations, can be related to many pathological conditions and may influence susceptibility to disease and drug treatment. The plausible effects of nnissense mutations range from affecting the macromolecular stability to perturbing macronnolecular interactions and cellular localization. Here we review the individual cases and genome-wide studies that illustrate the association between missense mutations and diseases. In addition, we emphasize that the molecular mechanisms of effects of mutations should be revealed in order to understand the disease origin. Finally, we report the current state-of-the-art methodologies that predict the effects of mutations on protein stability, the hydrogen bond network, pH dependence, conformational dynamics and protein function. Published by Elsevier Ltd.
C1 [Stefl, Shannon; Petukh, Marharyta; Alexov, Emil] Clemson Univ, Dept Phys, Clemson, SC 29634 USA.
[Nishi, Hafumi; Panchenko, Anna R.] NIH, Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA.
RP Panchenko, AR (reprint author), NIH, Natl Lib Med, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA.
EM panch@ncbi.nlm.nih.gov; ealexov@clemson.edu
OI Nishi, Hafumi/0000-0002-0846-0330
FU National Institutes of Health [R01GM093937]; Intramural Research Program
of the National Library of Medicine at the US National Institutes of
Health
FX S.S., M.P, and E.A. acknowledge the support from the National Institutes
of Health grant number R01GM093937. H.N. and A.R.P. were supported by
the Intramural Research Program of the National Library of Medicine at
the US National Institutes of Health.
NR 192
TC 46
Z9 47
U1 5
U2 28
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0022-2836
EI 1089-8638
J9 J MOL BIOL
JI J. Mol. Biol.
PD NOV 1
PY 2013
VL 425
IS 21
BP 3919
EP 3936
PG 18
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 242QM
UT WOS:000326257100003
PM 23871686
ER
PT J
AU Hamasaki-Katagiri, N
Salari, R
Wu, A
Ql, Y
Schiller, T
Filiberto, AC
Schisterman, EF
Komar, AA
Przytycka, TM
Kimchi-Sarfaty, C
AF Hamasaki-Katagiri, Nobuko
Salari, Raheleh
Wu, Andrew
Ql, Yini
Schiller, Tal
Filiberto, Amanda C.
Schisterman, Enrique F.
Komar, Anton A.
Przytycka, Teresa M.
Kimchi-Sarfaty, Chava
TI A Gene-Specific Method for Predicting Hemophilia-Causing Point Mutations
SO JOURNAL OF MOLECULAR BIOLOGY
LA English
DT Article
ID SINGLE-NUCLEOTIDE POLYMORPHISM; COAGULATION-FACTOR-VIII; MISSENSE
MUTATIONS; PROTEIN; DISEASE; RNA; PHOSPHORYLATION; IDENTIFICATION;
VARIANTS; RESOURCE
AB A fundamental goal of medical genetics is the accurate prediction of genotype phenotype correlations. As an approach to develop more accurate in silico tools for prediction of disease-causing mutations of structural proteins, we present a gene- and disease-specific prediction tool based on a large systematic analysis of missense mutations from hemophilia A (HA) patients. Our HA-specific prediction tool, HApredictor, showed disease prediction accuracy comparable to other publicly available prediction software. In contrast to those methods, its performance is not limited to non-synonymous mutations. Given the role of synonymous mutations in disease and drug codon optimization, we propose that utilizing a gene- and disease-specific method can be highly useful to make functional predictions possible even for synonymous mutations. Incorporating computational metrics at both nucleotide and amino acid levels along with multiple protein sequence/structure alignment significantly improved the predictive performance of our tool. HApredictor is freely available for download at http://www.ncbi.nlm.nih.gov/CBBresearch/Przytycka/HA_Predict/index.htm. Published by Elsevier Ltd.
C1 [Hamasaki-Katagiri, Nobuko; Wu, Andrew; Ql, Yini; Kimchi-Sarfaty, Chava] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA.
[Salari, Raheleh] Stanford Univ, Dept Comp Sci, Stanford, CA 94305 USA.
[Filiberto, Amanda C.; Schisterman, Enrique F.] NICHHD, Epidemiol Branch, NIH, Bethesda, MD 20892 USA.
[Komar, Anton A.] Cleveland State Univ, Dept Biol, Ctr Gene Regulat Hlth & Dis, Cleveland, OH 44115 USA.
[Przytycka, Teresa M.] NCI, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA.
RP Kimchi-Sarfaty, C (reprint author), 29 Lincoln Dr, Bethesda, MD 20892 USA.
EM Chava.kimchi-sarfaty@fda.hhs.gov
FU National Institutes of Health Intramural Research Funding (National
Library of Medicine); Natural Sciences and Engineering Research Council
Postdoctoral Fellowships
FX We would like to thank Ms. Erin Needlman, Ms. Natasha Nelson, Mr. Max
Katz, Mr. Jeong Lee, Mr. Stephen Gross, and Mr. Matt landoli for helping
with construction of datasets. We are grateful to Ms. Sandra C. Tseng,
Dr. Ryan Hunt, Dr. Zuben Sauna (Center for Biologics Evaluation and
Research, Food and Drug Administration), Dr. Deanna Church, and Mr. John
Garner (NCBI, National Institutes of Health) for insightful commentary.
We thank Dr. Geoffrey Kemball-Cook (University College London) for
maintaining HADB, data from which is now included in CHAMP. The findings
and conclusions in this article have not been formally disseminated by
the Food and Drug Administration and should not be construed to
represent any agency determination or policy. T.M.P. is supported by
National Institutes of Health Intramural Research Funding (National
Library of Medicine). R.S. was funded partially by Natural Sciences and
Engineering Research Council Postdoctoral Fellowships.
NR 33
TC 9
Z9 9
U1 2
U2 14
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 0022-2836
EI 1089-8638
J9 J MOL BIOL
JI J. Mol. Biol.
PD NOV 1
PY 2013
VL 425
IS 21
BP 4023
EP 4033
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 242QM
UT WOS:000326257100011
PM 23920358
ER
PT J
AU Xu, Z
Chen, WY
Merke, DP
McDonnell, NB
AF Xu, Zhi
Chen, Wuyan
Merke, Deborah P.
McDonnell, Nazli B.
TI Comprehensive Mutation Analysis of the CYP21A2 Gene An Efficient
Multistep Approach to the Molecular Diagnosis of Congenital Adrenal
Hyperplasia
SO JOURNAL OF MOLECULAR DIAGNOSTICS
LA English
DT Article
ID STEROID 21-HYDROXYLASE DEFICIENCY; DEPENDENT PROBE AMPLIFICATION;
CHIMERIC CYP21P/CYP21 GENE; POLYMERASE-CHAIN-REACTION;
EHLERS-DANLOS-SYNDROME; QUANTITATIVE PCR; LARGE COHORT; RCCX MODULE;
HYPERPLASIA; DELETION
AB Congenital adrenal hyperplasia, due to 21-hydroxylase deficiency (21-OHD) is an autosomal recessive disorder of adrenal steroidogenesis caused by mutations in the CYP21A2 gene. Direct comparison of established and novel methodologies of CYP21A2 genetic analysis in a large cohort representing a wide range of genotypes has not been previously reported. We genotyped a cohort of 129 unrelated patients with 21-OHD, along with 145 available parents, using Southern blot (SB) analysis, multiplex ligation-dependent probe amplification (MLPA), PCR-based restriction fragment length polymorphism (RFLP) analysis, multiplex minisequencing and conversion-specific PCR, duplication-specific amplification, and DNA sequencing. CYP21A2 genotyping identified four duplicated CYP21A2 genes (1.53%) and 79 chimeric CYP21A1P/CYP21A2 genes (30.15%). Parental SB data were essential for determining the CYP21 haplotype in three cases, whereas PCR-based RFLP analysis was necessary for MLPA results to be accurately interpreted in the majority of cases. The comparison of different methods in detecting deletion and duplication showed that MLPA with PCR-based RFLP was comparable with SB analysis, with parental data of 100% sensitivity and specificity. DNA sequencing was required for the identification of 16 (6.1%) rare point mutations and determination of clinically significant chimera junction sites. MLPA with PCR-based RFLP analysis is an excellent substitute for SB analysis in detecting CYP21A2 deletion and duplication and a combination of MLPA, PCR-based RFLP, duplication-specific amplification, and DNA sequencing is a convenient and comprehensive strategy for mutation analysis of the CYP21A2 gene in patients with 21-OHD.
C1 [Xu, Zhi; Chen, Wuyan; McDonnell, Nazli B.] NIA, Lab Clin Invest, Bethesda, MD 20892 USA.
[Merke, Deborah P.] Natl Inst Hlth Clin Ctr, Bethesda, MD USA.
[Merke, Deborah P.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Program Dev Endocrinol & Genet, Bethesda, MD USA.
RP McDonnell, NB (reprint author), NIA, Lab Clin Invest, Biomed Res Ctr, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM mcdonnellna@grc.nia.nih.gov
RI Xu, Zhi/I-2546-2012
FU NTH; National Institute on Aging; Clinical Center; Eunice Kennedy
Shriver National Institute of Child Health and Human Development
FX Supported by the Intramural Research Programs of the NTH, National
Institute on Aging, the Clinical Center, and the Eunice Kennedy Shriver
National Institute of Child Health and Human Development.
NR 40
TC 5
Z9 6
U1 1
U2 10
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1525-1578
EI 1943-7811
J9 J MOL DIAGN
JI J. Mol. Diagn.
PD NOV
PY 2013
VL 15
IS 6
BP 745
EP 753
DI 10.1016/j.jmoldx.2013.06.001
PG 9
WC Pathology
SC Pathology
GA 248BF
UT WOS:000326668000003
PM 24071710
ER
PT J
AU Church, D
Funke, B
Hegde, M
Chao, C
Trow, J
Slotta, D
Halavi, M
Meric, PA
Ananiev, V
Frishberg, D
Rubinstein, W
da Silva, C
Gowrisankar, S
Ajay, S
Chapman, B
Compton, J
Dames, S
Das, S
Feng, Y
Hambuch, T
Kulkarni, S
Mao, R
O'Fallon, BD
Shrivastava, S
Toji, L
Zhang, V
Zook, J
Kalman, L
AF Church, D.
Funke, B.
Hegde, M.
Chao, C.
Trow, J.
Slotta, D.
Halavi, M.
Meric, P. A.
Ananiev, V.
Frishberg, D.
Rubinstein, W.
da Silva, C.
Gowrisankar, S.
Ajay, S.
Chapman, B.
Compton, J.
Dames, S.
Das, S.
Feng, Y.
Hambuch, T.
Kulkarni, S.
Mao, R.
O'Fallon, B. D.
Shrivastava, S.
Toji, L.
Zhang, V.
Zook, J.
Kalman, L.
TI Development of Consensus Reference Material Tools for Clinical
Next-Generation Sequencing Tests
SO JOURNAL OF MOLECULAR DIAGNOSTICS
LA English
DT Meeting Abstract
CT Annual Meeting of the Association-for-Molecular-Pathology (AMP)
CY NOV 14-16, 2013
CL Phoenix, AZ
SP Assoc Mol Pathol
C1 [Church, D.] NIH, Bethesda, MD 20892 USA.
[Funke, B.] Massachusetts Gen Hosp, Cambridge, MA USA.
[Funke, B.] Harvard Univ, Sch Med, Cambridge, MA 02138 USA.
[Hegde, M.; da Silva, C.] Emory Univ, Sch Med, Atlanta, GA USA.
[Chao, C.; Trow, J.; Slotta, D.; Halavi, M.; Meric, P. A.; Ananiev, V.; Frishberg, D.; Rubinstein, W.] NIH, Bethesda, MD 20892 USA.
[Gowrisankar, S.] Partners Healthcare Ctr Personalized Genet Med, Cambridge, MA USA.
[Ajay, S.; Hambuch, T.] Illumina, San Diego, CA USA.
[Chapman, B.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
[Compton, J.] GeneDx Inc, Gaithersburg, MD USA.
[Dames, S.; Mao, R.; O'Fallon, B. D.] ARUP Labs, Salt Lake City, UT USA.
[Das, S.] Univ Chicago, Chicago, IL 60637 USA.
[Feng, Y.; Zhang, V.] Baylor Coll Med, Houston, TX 77030 USA.
[Kulkarni, S.; Shrivastava, S.] Washington Univ, Sch Med, St Louis, MO USA.
[Toji, L.] Coriell Inst Med Res, Camden, NJ USA.
[Zook, J.] NIST, Gaithersburg, MD 20899 USA.
[Kalman, L.] Ctr Dis Control & Prevent, Atlanta, GA USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1525-1578
EI 1943-7811
J9 J MOL DIAGN
JI J. Mol. Diagn.
PD NOV
PY 2013
VL 15
IS 6
BP 847
EP 847
PG 1
WC Pathology
SC Pathology
GA 248BF
UT WOS:000326668000032
ER
PT J
AU Rubinstein, WS
Kattman, BL
Malheiro, AJ
Lee, J
Hem, V
Ovetsky, M
Song, G
Maglott, D
AF Rubinstein, W. S.
Kattman, B. L.
Malheiro, A. J.
Lee, J.
Hem, V.
Ovetsky, M.
Song, G.
Maglott, D.
TI The NIH Genetic Testing Registry: A Survey of the Genetic Testing
Landscape
SO JOURNAL OF MOLECULAR DIAGNOSTICS
LA English
DT Meeting Abstract
CT Annual Meeting of the Association-for-Molecular-Pathology (AMP)
CY NOV 14-16, 2013
CL Phoenix, AZ
SP Assoc Mol Pathol
C1 [Rubinstein, W. S.; Kattman, B. L.; Malheiro, A. J.; Lee, J.; Hem, V.; Ovetsky, M.; Song, G.; Maglott, D.] 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 2013
VL 15
IS 6
BP 853
EP 853
PG 1
WC Pathology
SC Pathology
GA 248BF
UT WOS:000326668000054
ER
PT J
AU Castellar, ERP
Jaffe, ES
Said, J
Swerdlow, SH
Ketterling, RP
Knudson, RA
Sidhu, JS
Hsi, ED
Karikehalli, S
Jiang, L
Vasmatzis, G
Gibson, SE
Ondrejka, S
Nicolae, A
Grogg, KL
Allmer, C
Ristow, KM
Macon, WR
Law, ME
Cerhan, JR
Habermann, TM
Ansell, SM
Dogan, A
Maurer, MJ
Feldman, AL
AF Castellar, E. R. Parrilla
Jaffe, E. S.
Said, J.
Swerdlow, S. H.
Ketterling, R. P.
Knudson, R. A.
Sidhu, J. S.
Hsi, E. D.
Karikehalli, S.
Jiang, L.
Vasmatzis, G.
Gibson, S. E.
Ondrejka, S.
Nicolae, A.
Grogg, K. L.
Allmer, C.
Ristow, K. M.
Macon, W. R.
Law, M. E.
Cerhan, J. R.
Habermann, T. M.
Ansell, S. M.
Dogan, A.
Maurer, M. J.
Feldman, A. L.
TI Genetic Risk Stratification of CD30-Positive Peripheral T-Cell
Lymphomas: Results of a Multi-Institutional Study
SO JOURNAL OF MOLECULAR DIAGNOSTICS
LA English
DT Meeting Abstract
CT Annual Meeting of the Association-for-Molecular-Pathology (AMP)
CY NOV 14-16, 2013
CL Phoenix, AZ
SP Assoc Mol Pathol
C1 [Castellar, E. R. Parrilla; Ketterling, R. P.; Knudson, R. A.; Jiang, L.; Vasmatzis, G.; Grogg, K. L.; Allmer, C.; Ristow, K. M.; Macon, W. R.; Law, M. E.; Cerhan, J. R.; Habermann, T. M.; Ansell, S. M.; Dogan, A.; Maurer, M. J.; Feldman, A. L.] Mayo Clin, Rochester, MN USA.
[Jaffe, E. S.; Nicolae, A.] NCI, Bethesda, MD 20892 USA.
[Said, J.] Univ Calif Los Angeles, Los Angeles, CA USA.
[Swerdlow, S. H.; Gibson, S. E.] Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA.
[Sidhu, J. S.] United Hlth Serv Hosp, Johnson City, NY USA.
[Hsi, E. D.; Ondrejka, S.] Cleveland Clin, Cleveland, OH 44106 USA.
[Karikehalli, S.] Centrex Clin Labs, Utica, NY USA.
RI Jaffe, Elaine/G-8984-2014
OI Jaffe, Elaine/0000-0003-4632-0301
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1525-1578
EI 1943-7811
J9 J MOL DIAGN
JI J. Mol. Diagn.
PD NOV
PY 2013
VL 15
IS 6
BP 860
EP 860
PG 1
WC Pathology
SC Pathology
GA 248BF
UT WOS:000326668000080
ER
PT J
AU Lenoir, M
Kiyatkin, EA
AF Lenoir, Magalie
Kiyatkin, Eugene A.
TI Intravenous nictotine injection induces rapid, experience-dependent
sensitization of glutamate release in the ventral tegmental area and
nucleus accumbens
SO JOURNAL OF NEUROCHEMISTRY
LA English
DT Article
DE electrochemistry; enzyme-based glutamate biosensors;
experience-dependent neuroplasticity of glutamate neurotransmission;
glutamate release
ID STRIATAL NEURONAL-ACTIVITY; EXCITATORY AMINO-ACIDS; SENSORY
NERVE-ENDINGS; EXTRACELLULAR GLUTAMATE; LOCOMOTOR SENSITIZATION;
DOPAMINERGIC-NEURONS; UNRESTRAINED RATS; SUBSTANTIA-NIGRA; NICOTINE;
BRAIN
AB Although numerous data suggest that glutamate (GLU) is involved in mediating the neural effects of nicotine, direct data on nicotine-induced changes in GLU release are still lacking. Here, we used high-speed amperometry with enzyme-based GLU and enzyme-free GLU-null biosensors to examine changes in extracellular GLU levels in the ventral tegmental area (VTA) and nucleus accumbens shell (NAcc) induced by intravenous nicotine in a low, behaviorally active dose (30g/kg) in freely moving rats. Using this approach, we found that the initial nicotine injection in drug-naive conditions induces rapid, transient, and relatively small GLU release (similar to 90nM; latency similar to 15s, duration similar to 60s) that is correlative in the VTA and NAcc. Following subsequent nicotine injections within the same session, this phasic GLU release was supplemented by stronger tonic increases in GLU levels (100-300nM) that paralleled increases in drug-induced locomotor activation. GLU responses induced by repeated nicotine injections were more phasic and stronger in the NAcc than in VTA. Therefore, GLU is phasically released within the brain's reinforcement circuit following intravenous nicotine administration. Robust enhancement of nicotine-induced GLU responses following repeated injections suggests this change as an important mediator of sensitized behavioral and neural effects of nicotine.
C1 [Lenoir, Magalie; Kiyatkin, Eugene A.] NIDA, In Vivo Electrophysiol Unit, Behav Neurosci Branch, Intramural Res Program,NIH,DHHS, Baltimore, MD 21224 USA.
RP Kiyatkin, EA (reprint author), NIDA, In Vivo Electrophysiol Unit, Behav Neurosci Branch, Intramural Res Program,NIH,DHHS, 333 Cassell Dr, Baltimore, MD 21224 USA.
EM ekiyatki@intra.nida.nih.gov
FU Intramural Research Program of NIDA-IRP
FX This study was supported by the Intramural Research Program of NIDA-IRP.
We thank Dr Ken T. Wakabayashi and Stephanie Myal for valuable comments
on the content and language of this manuscript as well as assistance in
data analysis.
NR 50
TC 6
Z9 7
U1 2
U2 5
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 2013
VL 127
IS 4
BP 541
EP 551
DI 10.1111/jnc.12450
PG 11
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 245ME
UT WOS:000326467000014
PM 24032718
ER
PT J
AU Kweon, SS
Shu, XO
Xiang, YB
Cai, H
Yang, G
Ji, BT
Li, HL
Gao, YT
Zheng, W
Epplein, M
AF Kweon, Sun-Seog
Shu, Xiao-Ou
Xiang, Yongbing
Cai, Hui
Yang, Gong
Ji, Bu-Tian
Li, Honglan
Gao, Yu-Tang
Zheng, Wei
Epplein, Meira
TI Intake of Specific Nonfermented Soy Foods May Be Inversely Associated
with Risk of Distal Gastric Cancer in a Chinese Population
SO JOURNAL OF NUTRITION
LA English
DT Article
ID HELICOBACTER-PYLORI INFECTION; SHANGHAI WOMENS HEALTH; STOMACH-CANCER;
PHASEOLUS-VULGARIS; COLORECTAL-CANCER; DIETARY FACTORS; GLYCEMIC LOAD;
MENS HEALTH; IN-VITRO; ESTROGEN
AB Because the association between soy consumption and gastric cancer is inconsistent, we evaluated the putative preventive effect of soy food on gastric cancer risk in the Shanghai Women's and Men's Health Studies, comprising a total of 128,687 participants. Intake of nonfermented soy foods was estimated using 2 validated food-frequency questionnaires. HRs were calculated with 95% CIs for intake amounts of total nonfermented soy food intake, soy protein, and isoflavones as well as individual soy food groups using Cox proportional hazards regression. A total of 493 distal gastric cancer cases were identified by 2010. Although all risk estimates for summary measures of soy food intake above the lowest quartile (quartile 1) were suggestive of a protective effect, no statistically significant associations with risk of distal gastric cancer were found. Among the separate soy food groups, significant reductions in risk of distal gastric cancer by increasing intake of tofu were found in men in quartile 2 (HR: 0.59; 95% Cl: 0.40, 0.86), quartile 3 (HR: 0.62; 95% Cl: 0.44, 0.88), and quartile 4 (HR: 0.64; 95% CI: 0.42, 0.99), resulting in a significant trend (P-trend = 0.02). Dry bean intake was also inversely associated with decreased risk of gastric cancer, but in postmenopausal women only [quartile 2 (HR: 0.54; 95% CI: 0.30, 0.96); quartile 3 (HR: 0.90; 95% CI: 0.64, 1.27); and quartile 4 (HR: 0.63; 95% CI: 0.43, 0.91)1, resulting in a significant trend (P-trend = 0.03). Overall, our study found no statistically significant association between nonfermented soy food intake and distal gastric cancer risk, though the data supported the hypothesis that tofu may protect against distal gastric cancer in men and dry bean consumption may decrease the risk of gastric cancer in postmenopausal women.
C1 [Kweon, Sun-Seog; Shu, Xiao-Ou; Cai, Hui; Yang, Gong; Zheng, Wei; Epplein, Meira] Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Div Epidemiol,Dept Med, Nashville, TN 37212 USA.
[Kweon, Sun-Seog] Chonnam Natl Univ, Sch Med, Dept Prevent Med, Kwangju, South Korea.
[Xiang, Yongbing; Li, Honglan; Gao, Yu-Tang] Shanghai Jiao Tong Univ, Shanghai Canc Inst, Renji Hosp, Dept Epidemiol,Sch Med, Shanghai 200030, Peoples R China.
[Ji, Bu-Tian] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
RP Epplein, M (reprint author), Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Div Epidemiol,Dept Med, Nashville, TN 37212 USA.
EM meira.epplein@vanderbilt.edu
OI Epplein, Meira/0000-0001-5646-6430; KWEON, SUNSEOG/0000-0003-2378-8550
FU National Cancer Institute [R37 CA70867, R01 CA82729]
FX Supported by National Cancer Institute grants R37 CA70867 and R01
CA82729.
NR 56
TC 7
Z9 7
U1 2
U2 15
PU AMER SOC NUTRITION-ASN
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-3166
EI 1541-6100
J9 J NUTR
JI J. Nutr.
PD NOV
PY 2013
VL 143
IS 11
BP 1736
EP 1742
DI 10.3945/jn.113.177675
PG 7
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 240VQ
UT WOS:000326126200006
PM 23986366
ER
PT J
AU Beydoun, MA
Kuczmarski, MTF
Beydoun, HA
Hibbeln, JR
Evans, MK
Zonderman, AB
AF Beydoun, May A.
Kuczmarski, Marie T. Fanelli
Beydoun, Hind A.
Hibbeln, Joseph R.
Evans, Michele K.
Zonderman, Alan B.
TI omega-3 Fatty Acid Intakes Are Inversely Related to Elevated Depressive
Symptoms among United States Women
SO JOURNAL OF NUTRITION
LA English
DT Article
ID MULTIPLE-PASS METHOD; POLYUNSATURATED FATTY-ACIDS; VITAMIN-E LEVELS;
MAJOR DEPRESSION; FISH CONSUMPTION; DIETARY-INTAKE; FOLLOW-UP;
ATHEROSCLEROSIS RISK; SOCIOECONOMIC-STATUS; UNIPOLAR DEPRESSION
AB Evidence that depressive symptoms are inversely related to n-3 (w-3) fatty acids is growing among United States adults. We assessed whether self-reported depressive symptoms were inversely associated with n-3 fatty acid intakes by using a cross-sectional study in 1746 adults (aged 30-65 y) in Baltimore City, MD (2004-2009). The 20-item Center for Epidemiologic Studies-Depression Scale (CES-D) was used, with a CES-D score >= 16 suggestive of elevated depressive symptoms (EDS). By using the mean of two 24-h dietary recalls, n-3 highly unsaturated fatty acids (HUFAs; carbons), n-3 polyunsaturated fatty acids (PUFAs; >= 18 carbons), and plausible ratios with n-6 (omega 6) fatty acids were estimated. EDS prevalence was 18.1% among men and 25.6% among women. In women, the uppermost tertile (tertile 3) of n-3 PUFAs (compared with tertile 1) was associated with reduced odds of EDS by 49%, with a substantial sex differential. The n-3 PUFA:n-6:PUFA ratio was inversely related to EDS among women (tertile 2 vs. tertile 1, OR: 0.74; 95% CI: 0.41, 1.32; tertile 3 vs. tertile 1, OR: 0.47; 95% Cl: 0.27, 0.83). A similar pattern was noted for n-3 HUFA:n-6 HUFA among women. For CES-D subscales, n-3 PUFA 1% of energy) was inversely related to somatic complaints, whereas positive affect was directly related to n-3 HUFA (% of energy; total population and among women), n-3 HUFA:n-6 HUFA (women), and n-3 HUFA:n-6 PUFA (total population and among women). In sum, among United States women, higher intakes of n-3 fatty acids [absolute (n-3) and relative to n-6 fatty acids (n-3:n-6)) were associated with lower risk of elevated depressive symptoms, specifically in domains of somatic complaints (mainly n-3 PUFAs) and positive affect (mainly n-3 HUFAs).
C1 [Beydoun, May A.; Evans, Michele K.; Zonderman, Alan B.] NIA, Intramural Res Program, Baltimore, MD 21224 USA.
[Kuczmarski, Marie T. Fanelli] Univ Delaware, Dept Behav Hlth & Nutr, Newark, DE USA.
[Beydoun, Hind A.] Eastern Virginia Med Sch, Grad Program Publ Hlth, Norfolk, VA 23501 USA.
[Hibbeln, Joseph R.] NIAAA, Nutr Neurosci Sect, Intramural Res Program, NIH, Bethesda, MD USA.
RP Beydoun, MA (reprint author), NIA, Intramural Res Program, Baltimore, MD 21224 USA.
EM baydounm@mail.nih.gov
FU National Institute on Aging, Intramural Research Program NIA/NIH/IRP
FX Supported by the National Institute on Aging, Intramural Research
Program NIA/NIH/IRP).
NR 80
TC 17
Z9 18
U1 1
U2 22
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 2013
VL 143
IS 11
BP 1743
EP 1752
DI 10.3945/jn.113.179119
PG 10
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 240VQ
UT WOS:000326126200007
PM 24005610
ER
PT J
AU Nelson, WL
Suls, J
AF Nelson, Wendy L.
Suls, Jerry
TI New Approaches to Understand Cognitive Changes Associated With
Chemotherapy for Non-Central Nervous System Tumors
SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT
LA English
DT Article
DE Cancer; chemotherapy; cognitive impairment; neuropsychological testing;
computational modeling
ID BREAST-CANCER SURVIVORS; HIGH-DOSE CHEMOTHERAPY; CEREBRAL WHITE-MATTER;
OF-THE-LITERATURE; ADJUVANT CHEMOTHERAPY; ECOLOGICAL VALIDITY; SPATIAL
NAVIGATION; VIRTUAL-REALITY; POOLED ANALYSIS; BONE-MARROW
AB Context. Researchers have described a constellation of cognitive deficits (e. g., impairments in executive functions, working memory, attention, and information-processing speed) associated with cancer treatment, and specifically chemotherapy, for non-central nervous system tumors. However, findings have been inconsistent, largely because of measurement and study design issues.
Objectives. To propose ways for researchers to more clearly delineate and characterize the mild cognitive deficits and related outcomes that appear to affect a subset of cancer patients and suggest methods to make more effective use of the existing data to understand risk factors for impaired neuropsychological functioning.
Methods. We examined the literature on the relationship between chemotherapy and cognitive impairment, as well as related literature on neuropsychological measurement, structural and functional neuroimaging, alternative measures of health outcomes, and integrative data analysis.
Results. A more comprehensive picture of cognitive functioning might be obtained by incorporating nontraditional ecological measures, self-reports, computational modeling, new neuroimaging methods, and markers of occupational functioning. Case-control and integrative data analytic techniques potentially could leverage existing data to identify risk factors for cognitive dysfunction and test hypotheses about the etiology of these effects.
Conclusion. There is a need to apply new research approaches to understand the real-world functional implications of the cognitive side effects of chemotherapy to develop and implement strategies to minimize and remediate these effects before, during, and after cancer treatment. (C) 2013 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.
C1 [Nelson, Wendy L.] NCI, Div Canc Control & Populat Sci, Behav Res Program, Basic Biobehav & Psychol Sci Branch, Bethesda, MD 20892 USA.
[Suls, Jerry] Univ Iowa, Dept Psychol, Iowa City, IA USA.
RP Nelson, WL (reprint author), NCI, Div Canc Control & Populat Sci, Behav Res Program, Basic Biobehav & Psychol Sci Branch, 6130 Executive Blvd,EPN 4064, Bethesda, MD 20892 USA.
EM nelsonw@mail.nih.gov
NR 120
TC 12
Z9 12
U1 3
U2 15
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 2013
VL 46
IS 5
BP 707
EP 721
DI 10.1016/j.jpainsymman.2012.11.005
PG 15
WC Health Care Sciences & Services; Medicine, General & Internal; Clinical
Neurology
SC Health Care Sciences & Services; General & Internal Medicine;
Neurosciences & Neurology
GA 242JQ
UT WOS:000326236900014
PM 23522517
ER
PT J
AU Nomani, F
Kamal, AK
AF Nomani, Fauzia
Kamal, Ayeesha Kamran
TI Citicoline in the treatment of acute ischaemic stroke: an international,
randomized, multicentre, placebo-controlled study (ICTUS trial)Is the
use of Citicoline is beneficial for acute ischaemic stroke?
SO JOURNAL OF THE PAKISTAN MEDICAL ASSOCIATION
LA English
DT Editorial Material
C1 [Kamal, Ayeesha Kamran] Aga Khan Univ Hosp, Stroke Serv, Karachi, Pakistan.
Aga Khan Univ Hosp, Vasc Fellowship Program, Int Cerebrovasc Translat Clin Res Training Progra, Fogarty Int Ctr, Karachi, Pakistan.
Aga Khan Univ Hosp, Natl Inst Neurol Disorders & Stroke, Karachi, Pakistan.
RP Kamal, AK (reprint author), Aga Khan Univ Hosp, Stroke Serv, Karachi, Pakistan.
EM ayeesha.kamal@aku.edu
NR 1
TC 0
Z9 1
U1 0
U2 3
PU PAKISTAN MEDICAL ASSOC
PI KARACHI
PA PMA HOUSE, AGA KHAN III RD, KARACHI, 00000, PAKISTAN
SN 0030-9982
J9 J PAK MED ASSOC
JI J. Pak. Med. Assoc.
PD NOV
PY 2013
VL 63
IS 11
BP 1445
EP 1445
PG 1
WC Medicine, General & Internal; Medicine, Research & Experimental
SC General & Internal Medicine; Research & Experimental Medicine
GA 244XD
UT WOS:000326422600031
PM 24392540
ER
PT J
AU Tonelli, MA
Wanner, C
Cass, A
Garg, AX
Holdaas, H
Jardine, AG
Jiang, LX
Kronenberg, F
Parekh, RS
Shoji, T
Walker, RJ
Kasiske, BL
Wheeler, DC
Upadhyay, A
Balk, EM
Earley, A
Haynes, S
Lamont, J
AF Tonelli, Marcello A.
Wanner, Christoph
Cass, Alan
Garg, Amit X.
Holdaas, Hallvard
Jardine, Alan G.
Jiang, Lixin
Kronenberg, Florian
Parekh, Rulan S.
Shoji, Tetsuo
Walker, Robert J.
Kasiske, Bertram L.
Wheeler, David C.
Upadhyay, Ashish
Balk, Ethan M.
Earley, Amy
Haynes, Shana
Lamont, Jenny
TI Introduction: The case for updating and context
SO KIDNEY INTERNATIONAL SUPPLEMENTS
LA English
DT Article
DE cholesterol; chronic kidney disease; clinical practice guideline;
dyslipidemia; evidence-based recommendation; KDIGO; systematic review;
triglycerides
ID DENSITY-LIPOPROTEIN CHOLESTEROL; CHRONIC KIDNEY-DISEASE; HETEROZYGOUS
FAMILIAL HYPERCHOLESTEROLEMIA; RANDOMIZED CONTROLLED-TRIAL; TYPE-2
DIABETES-MELLITUS; PLACEBO-CONTROLLED TRIAL; EDUCATION-PROGRAM
RECOMMENDATIONS; CLINICAL-PRACTICE GUIDELINES; CORONARY-HEART-DISEASE;
RENAL-TRANSPLANT RECIPIENTS
AB The 2013 Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline for Lipid Management in Chronic Kidney Disease (CKD) provides guidance on lipid management and treatment for all patients with CKD (non-dialysis-dependent, dialysis-dependent, kidney transplant recipients and children). This guideline contains chapters on the assessment of lipid status and treatment for dyslipidemia in adults and children. Development of the guideline followed an explicit process of evidence review and appraisal. Treatment approaches are addressed in each chapter and guideline recommendations are based on systematic reviews of relevant trials. Appraisal of the quality of the evidence and the strength of recommendations followed the GRADE approach. Ongoing areas of controversies and limitations of the evidence are discussed and additional suggestions are also provided for future research.
C1 [Tonelli, Marcello A.] Univ Alberta, Edmonton, AB T6G 2M7, Canada.
[Tonelli, Marcello A.] Univ Alberta & Hosp Civil Guadalajara, Guadalajara, Spain.
[Wanner, Christoph] Univ Wurzburg, Dept Med, Wurzburg, Germany.
[Cass, Alan] Menzies Sch Hlth Res, Darwin, NT, Australia.
[Cass, Alan] George Inst Global Hlth, Renal & Metab Div, Sydney, NSW, Australia.
[Garg, Amit X.] Univ Western Ontario, London, ON N6A 3K7, Canada.
[Garg, Amit X.] London Kidney Clin Res Unit, London, England.
[Holdaas, Hallvard] Natl Hosp Norway, Oslo Univ Hosp, Dept Transplant Med, Oslo, Norway.
[Jardine, Alan G.] Univ Glasgow, Glasgow G12 8QQ, Lanark, Scotland.
[Jardine, Alan G.] BHF Glasgow Cardiovasc Res Ctr, Renal Res Grp, Glasgow, Lanark, Scotland.
[Jardine, Alan G.] Undergrad Med Sch, Glasgow, Lanark, Scotland.
[Jiang, Lixin] Chinese Acad Med Sci, Beijing, Peoples R China.
[Jiang, Lixin] Peking Union Med Coll, Beijing, Peoples R China.
[Jiang, Lixin] Univ Oxford, Oxford OX1 2JD, England.
[Kronenberg, Florian] Univ Utah, Salt Lake City, UT USA.
[Kronenberg, Florian] Helmholtz Ctr, Inst Epidemiol, Munich, Germany.
[Kronenberg, Florian] Med Univ Innsbruck, Dept Med Genet Mol & Clin Pharmacol, A-6020 Innsbruck, Austria.
[Parekh, Rulan S.] Univ Toronto, Toronto, ON M5S 1A1, Canada.
[Parekh, Rulan S.] Hosp Sick Children, Toronto, ON M5G 1X8, Canada.
[Shoji, Tetsuo] Osaka City Univ, Grad Sch Med, Dept Geriatr & Vasc Med, Osaka 558, Japan.
[Shoji, Tetsuo] Osaka City Univ Hospital, Dept Internal Med 2, Osaka, Japan.
[Walker, Robert J.] Univ Otago, Christchurch, New Zealand.
[Walker, Robert J.] Univ Otago, Dunedin Sch Med, Christchurch, New Zealand.
[Walker, Robert J.] Healthcare Otago, Christchurch, New Zealand.
[Walker, Robert J.] Healthcare Otago, Nephrol, Christchurch, New Zealand.
[Kasiske, Bertram L.] Univ Minnesota, Minneapolis, MN 55455 USA.
[Kasiske, Bertram L.] NIH, Bethesda, MD USA.
[Wheeler, David C.] UCL, London WC1E 6BT, England.
[Upadhyay, Ashish] Boston Univ, Sch Med, Renal Sect, Boston, MA 02118 USA.
[Upadhyay, Ashish] Boston Univ, Sch Med, Internal Med Residency Program, Boston, MA 02118 USA.
[Upadhyay, Ashish; Balk, Ethan M.] Tufts Univ, Sch Med, Medford, MA USA.
[Upadhyay, Ashish] Tufts Med Ctr, William B Schwartz MD Div Nephrol, Medford, MA USA.
[Balk, Ethan M.; Earley, Amy; Haynes, Shana; Lamont, Jenny] Tufts Ctr Kidney Dis Guideline Dev & Implementat, Boston, MA USA.
[Balk, Ethan M.] Tufts Evidence Based Practice Ctr, Medford, MA USA.
RP Tonelli, MA (reprint author), Univ Alberta, Edmonton, AB T6G 2M7, Canada.
RI Kronenberg, Florian/B-1736-2008
OI Kronenberg, Florian/0000-0003-2229-1120
NR 114
TC 1
Z9 1
U1 1
U2 5
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 2157-1724
EI 2157-1716
J9 KIDNEY INT SUPPL
JI Kidney Int. Suppl.
PD NOV
PY 2013
VL 3
IS 3
BP 266
EP +
DI 10.1038/kisup.2013.32
PG 41
WC Urology & Nephrology
SC Urology & Nephrology
GA 245YT
UT WOS:000326502000002
ER
PT J
AU Silk, SB
Brown, P
AF Silk, Susan Brust
Brown, Patricia
TI Clarification of OLAW's position on rodent cage changes
SO LAB ANIMAL
LA English
DT Letter
C1 [Silk, Susan Brust; Brown, Patricia] NIH, Off Lab Anim Welf, Off Extramural Res, US Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
RP Silk, SB (reprint author), NIH, Off Lab Anim Welf, Off Extramural Res, US Dept Hlth & Human Serv, Bldg 10, Bethesda, MD 20892 USA.
EM olaw@od.nih.gov
NR 2
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0093-7355
EI 1548-4475
J9 LAB ANIMAL
JI Lab Anim.
PD NOV
PY 2013
VL 42
IS 11
BP 409
EP 409
PG 1
WC Veterinary Sciences
SC Veterinary Sciences
GA 245UB
UT WOS:000326488200012
PM 24150161
ER
PT J
AU Hu, XB
Wei, H
Xiang, LM
Chertov, O
Wayne, AS
Bera, TK
Pastan, I
AF Hu, Xiaobo
Wei, Hui
Xiang, Laiman
Chertov, Oleg
Wayne, Alan S.
Bera, Tapan K.
Pastan, Ira
TI Methylation of the DPH1 promoter causes immunotoxin resistance in acute
lymphoblastic leukemia cell line KOPN-8
SO LEUKEMIA RESEARCH
LA English
DT Article
DE DNA methylation; Drug resistance; ADP-ribosylation; Diphthamide
synthesis; Epigenetic regulation
ID PSEUDOMONAS-EXOTOXIN; SACCHAROMYCES-CEREVISIAE; DIPHTHERIA-TOXIN;
DIPHTHAMIDE BIOSYNTHESIS; MYELOID-LEUKEMIA; IN-VITRO; GENE; CANCER;
5-AZA-2'-DEOXYCYTIDINE; EXPRESSION
AB Moxetumomab pasudotox (HA22) is an immunotoxin with an anti-CD22 Fv fused to a portion of Pseudomonas exotoxin A that kills CD22 expressing ALL cells. HA22 produced significant responses in some cases of ALL. To understand how to increase response rate, we isolated HA22-resistant KOPN-8 cells and found that HA22 cannot inactivate elongation factor-2 (EF2) due to low levels of DPH1 RNA and protein. Resistance was associated with methylation of the CpG island in the DPH1 promoter. 5-Azacytidine prevented resistance and methylation of the CpG residues and merits evaluation to determine if it can increase the efficacy of HA22 in ALL. Published by Elsevier Ltd.
C1 [Hu, Xiaobo; Wei, Hui; Xiang, Laiman; Wayne, Alan S.; Bera, Tapan K.; Pastan, Ira] NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
[Chertov, Oleg] NCI, Prot Chem Lab, Adv Technol Program, SAIC Frederick,Frederick Natl Lab Canc Res, Frederick, MD 21701 USA.
[Wayne, Alan S.] NCI, Pediat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Pastan, I (reprint author), NCI, Mol Biol Lab, 37 Convent Dr,Room 5106, Bethesda, MD 20892 USA.
EM pastani@mail.nih.gov
FU NIH, NCI, Center for Cancer Research; NCI, NIH [HHSN261200800001E]
FX This research was supported in part by the Intramural Research Program
of the NIH, NCI, Center for Cancer Research, in part with federal funds
from the NCI, NIH, under contract No. HHSN261200800001E, and in part
with a Cooperative Research and Development Agreement with MedImmune,
LLC.
NR 39
TC 7
Z9 7
U1 0
U2 3
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0145-2126
J9 LEUKEMIA RES
JI Leuk. Res.
PD NOV
PY 2013
VL 37
IS 11
BP 1551
EP 1556
DI 10.1016/j.leukres.2013.08.005
PG 6
WC Oncology; Hematology
SC Oncology; Hematology
GA 242UV
UT WOS:000326269500029
PM 24070652
ER
PT J
AU Lasota, J
Xi, LQ
Coates, T
Dennis, R
Evbuomwan, MO
Wang, ZF
Raffeld, M
Miettinen, M
AF Lasota, Jerzy
Xi, Liqiang
Coates, Tiffany
Dennis, RaShonda
Evbuomwan, Moses O.
Wang, Zeng-Feng
Raffeld, Mark
Miettinen, Markku
TI No KRAS mutations found in gastrointestinal stromal tumors (GISTs):
molecular genetic study of 514 cases
SO MODERN PATHOLOGY
LA English
DT Article
DE GIST; KIT mutations; KRAS mutations; PDGFRA mutations; pyrosequencing;
Sanger sequencing
ID TYROSINE KINASE INHIBITORS; RAS GENE; BRAF MUTATIONS; CARCINOMA;
SARCOMA; RESISTANCE; BLADDER; EVENTS; HARVEY
AB Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. A great majority of GISTs is driven by pathological activation of KIT or platelet-derived growth factor receptor-alpha (PDGFRA), two closely related receptor tyrosine kinases. However, other genetic changes including gain-of-function BRAF mutations and loss of succinate dehydrogenase (SDH) complex activity have been identified in the subsets of KIT-, PDGFRA-wild type tumors. Genetic mutations affecting KIT, PDGFRA, BRAF and SDH complex functions are believed to be mutually exclusive events. Recently, KRAS codon 12 and 13 mutations were reported in a small subset of KIT or PDGFRA mutant GISTs. Moreover, in in vitro experiments, KIT mutants with concurrent KRAS mutation showed resistance to imatinib, a receptor tyrosine kinase inhibitor used in GIST treatment. The aim of this study was to evaluate a large cohort of GISTs to define frequency and clinical significance of KRAS mutations in this type of cancer. A well-characterized cohort of 514 GISTs was screened for KRAS mutations using Sanger sequencing (n = 450) and pyrosequencing (n = 64). In all, 350 gastric, 100 intestinal and 64 primary disseminated GISTs were analyzed. No KRAS mutations were found. In GIST, KRAS mutations are extremely rare if they exist (<0.2%). Thus, mutational activation of KRAS does not seem to play any significant role in the development and progression of this type of cancer.
C1 [Lasota, Jerzy; Xi, Liqiang; Coates, Tiffany; Dennis, RaShonda; Evbuomwan, Moses O.; Wang, Zeng-Feng; Raffeld, Mark; Miettinen, Markku] NCI, Pathol Lab, Bethesda, MD 20892 USA.
RP Lasota, J (reprint author), NCI, Pathol Lab, 9000 Rockville Pike,Bldg 10,Room B1B47, Bethesda, MD 20892 USA.
EM jerzy.lasota@nih.gov
FU NCI's Intramural Research Program
FX This work was supported in part by NCI's Intramural Research Program.
NR 22
TC 10
Z9 11
U1 0
U2 6
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 2013
VL 26
IS 11
BP 1488
EP 1491
DI 10.1038/modpathol.2013.89
PG 4
WC Pathology
SC Pathology
GA 248GV
UT WOS:000326686700009
PM 23702733
ER
PT J
AU Barbash, ZS
Weissman, JD
Campbell, JA
Mu, J
Singer, DS
AF Barbash, Zohar S.
Weissman, Jocelyn D.
Campbell, John A., Jr.
Mu, Jie
Singer, Dinah S.
TI Major Histocompatibility Complex Class I Core Promoter Elements Are Not
Essential for Transcription In Vivo
SO MOLECULAR AND CELLULAR BIOLOGY
LA English
DT Article
ID RNA-POLYMERASE-II; TRANSGENE COPY NUMBER; FUNCTIONAL-CHARACTERIZATION;
HUMAN GENOME; DNA-BINDING; GENE; EXPRESSION; INITIATOR; SEQUENCE;
PROTEIN
AB The role of core promoter elements in regulating transcription initiation is largely unknown for genes subject to complex regulation. Major histocompatibility complex class I genes are ubiquitously expressed and governed by tissue-specific and hormonal signals. Transcription initiates at multiple sites within the core promoter, which contains elements homologous to the canonical elements CCAAT, TATAA, Sp1 binding site (Sp1BS), and Initiator (Inr). To determine their functions, expression of class I transgenes with individually mutated elements was assessed. Surprisingly, all mutant promoters supported transcription. However, each mutated core promoter element had a distinct effect on expression: CAAT box mutations modulated constitutive expression in nonlymphoid tissues, whereas TATAA-like element mutations dysregulated transcription in lymphoid tissues. Inr mutations aberrantly elevated expression. Sp1BS element mutations resulted in variegated transgene expression. RNA polymerase II binding and histone H3K4me3 patterns correlated with transgene expression; H3K9me3 marks partially correlated. Whereas the wild-type, TATAA-like, and CAAT mutant promoters were activated by gamma interferon, the Sp1 and Inr mutants were repressed, implicating these elements in regulation of hormonal responses. These results lead to the surprising conclusion that no single element is required for promoter activity. Rather, each plays a distinct role in promoter activity, chromatin structure, tissue-specific expression, and extracellular signaling.
C1 [Barbash, Zohar S.; Weissman, Jocelyn D.; Campbell, John A., Jr.; Mu, Jie; Singer, Dinah S.] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA.
RP Singer, DS (reprint author), NCI, Expt Immunol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM dinah.singer@nih.gov
FU NIH, National Cancer Institute, Center for Cancer Research
FX This research was supported by the Intramural Research Program of the
NIH, National Cancer Institute, Center for Cancer Research.
NR 49
TC 4
Z9 4
U1 1
U2 4
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0270-7306
EI 1098-5549
J9 MOL CELL BIOL
JI Mol. Cell. Biol.
PD NOV
PY 2013
VL 33
IS 22
BP 4395
EP 4407
DI 10.1128/MCB.00553-13
PG 13
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 240LX
UT WOS:000326099000004
PM 24019072
ER
PT J
AU Laurent, G
de Boer, VCJ
Finley, LWS
Sweeney, M
Lu, H
Schug, TT
Cen, YN
Jeong, SM
Li, XL
Sauve, AA
Haigis, MC
AF Laurent, Gaelle
de Boer, Vincent C. J.
Finley, Lydia W. S.
Sweeney, Meredith
Lu, Hong
Schug, Thaddeus T.
Cen, Yana
Jeong, Seung Min
Li, Xiaoling
Sauve, Anthony A.
Haigis, Marcia C.
TI SIRT4 Represses Peroxisome Proliferator-Activated Receptor alpha
Activity To Suppress Hepatic Fat Oxidation
SO MOLECULAR AND CELLULAR BIOLOGY
LA English
DT Article
ID SILENCING PROTEIN SIR2; GENE-EXPRESSION; ACID OXIDATION;
ENERGY-METABOLISM; PPAR-ALPHA; DEACETYLASE; STRESS; FAMILY; LIVER; MICE
AB Sirtuins are a family of protein deacetylases, deacylases, and ADP-ribosyltransferases that regulate life span, control the onset of numerous age-associated diseases, and mediate metabolic homeostasis. We have uncovered a novel role for the mitochondrial sirtuin SIRT4 in the regulation of hepatic lipid metabolism during changes in nutrient availability. We show that SIRT4 levels decrease in the liver during fasting and that SIRT4 null mice display increased expression of hepatic peroxisome proliferator-activated receptor alpha (PPAR alpha) target genes associated with fatty acid catabolism. Accordingly, primary hepatocytes from SIRT4 knockout (KO) mice exhibit higher rates of fatty acid oxidation than wild-type hepatocytes, and SIRT4 overexpression decreases fatty acid oxidation rates. The enhanced fatty acid oxidation observed in SIRT4 KO hepatocytes requires functional SIRT1, demonstrating a clear cross talk between mitochondrial and nuclear sirtuins. Thus, SIRT4 is a new component of mitochondrial signaling in the liver and functions as an important regulator of lipid metabolism.
C1 [Laurent, Gaelle; de Boer, Vincent C. J.; Finley, Lydia W. S.; Sweeney, Meredith; Lu, Hong; Jeong, Seung Min; Haigis, Marcia C.] Harvard Univ, Sch Med, Dept Cell Biol, Paul F Glenn Labs Biol Mech Aging, Boston, MA 02114 USA.
[Schug, Thaddeus T.; Li, Xiaoling] NIEHS, Lab Signal Transduct, Res Triangle Pk, NC 27709 USA.
[Cen, Yana; Sauve, Anthony A.] Cornell Univ, Weill Med Coll, Dept Pharmacol, New York, NY 10021 USA.
RP Haigis, MC (reprint author), Harvard Univ, Sch Med, Dept Cell Biol, Paul F Glenn Labs Biol Mech Aging, Boston, MA 02114 USA.
EM marcia_haigis@hms.harvard.edu
RI de Boer, Vincent/F-4879-2010; Cen, Yana/F-4731-2014; de Boer,
Vincent/L-2196-2016
OI de Boer, Vincent/0000-0001-9928-1698; Cen, Yana/0000-0001-6436-5744;
FU Human Frontier Science Program; Netherlands Organization for Scientific
Research; Brookdale Leadership in Aging Fellowship; Ellison Medical
Foundation; NIA [R01/AG032375]; Glenn Foundation for Medical Research
FX G.L. was supported by a fellowship from the Human Frontier Science
Program. V.C.J.D.B. was supported by a Rubicon fellowship from the
Netherlands Organization for Scientific Research. M. C. H. was supported
by a Brookdale Leadership in Aging Fellowship, Ellison Medical
Foundation New Scholar Award, funding from NIA R01/AG032375, and the
Glenn Foundation for Medical Research.
NR 43
TC 24
Z9 30
U1 0
U2 9
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0270-7306
EI 1098-5549
J9 MOL CELL BIOL
JI Mol. Cell. Biol.
PD NOV
PY 2013
VL 33
IS 22
BP 4552
EP 4561
DI 10.1128/MCB.00087-13
PG 10
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 240LX
UT WOS:000326099000016
PM 24043310
ER
PT J
AU Baltanas, FC
Perez-Andres, M
Ginel-Picardo, A
Diaz, D
Jimeno, D
Liceras-Boillos, P
Kortum, RL
Samelson, LE
Orfao, A
Santos, E
AF Baltanas, Fernando C.
Perez-Andres, Martin
Ginel-Picardo, Alicia
Diaz, David
Jimeno, David
Liceras-Boillos, Pilar
Kortum, Robert L.
Samelson, Lawrence E.
Orfao, Alberto
Santos, Eugenio
TI Functional Redundancy of Sos1 and Sos2 for Lymphopoiesis and Organismal
Homeostasis and Survival
SO MOLECULAR AND CELLULAR BIOLOGY
LA English
DT Article
ID B-CELL DEVELOPMENT; RAS ACTIVATION; T-CELLS; PATHWAY; DIFFERENTIATION;
EXPRESSION; LEUKEMIA
AB Sos1 and Sos2 are ubiquitously expressed, universal Ras guanine nucleotide exchange factors (Ras-GEFs) acting in multiple signal transduction pathways activated by upstream cellular kinases. The embryonic lethality of Sos1 null mutants has hampered ascertaining the specific in vivo contributions of Sos1 and Sos2 to processes controlling adult organism survival or development of hematopoietic and nonhematopoietic organs, tissues, and cell lineages. Here, we generated a tamoxifen-inducible Sos1-null mouse strain allowing analysis of the combined disruption of Sos1 and Sos2 (Sos1/2) during adulthood. Sos1/2 double-knockout (DKO) animals died precipitously, whereas individual Sos1 and Sos2 knockout (KO) mice were perfectly viable. A reduced percentage of total bone marrow precursors occurred in single-KO animals, but a dramatic depletion of B-cell progenitors was specifically detected in Sos1/2 DKO mice. We also confirmed a dominant role of Sos1 over Sos2 in early thymocyte maturation, with almost complete thymus disappearance and dramatically higher reduction of absolute thymocyte counts in Sos1/2 DKO animals. Absolute counts of mature B and T cells in spleen and peripheral blood were unchanged in single-KO mutants, while significantly reduced in Sos1/2 DKO mice. Our data demonstrate functional redundancy between Sos1 and Sos2 for homeostasis and survival of the full organism and for development and maturation of T and B lymphocytes.
C1 [Baltanas, Fernando C.; Ginel-Picardo, Alicia; Jimeno, David; Liceras-Boillos, Pilar; Santos, Eugenio] Univ Salamanca, CSIC, Inst Biol Mol & Celular Canc, Ctr Invest Canc,Lab 1, E-37008 Salamanca, Spain.
[Perez-Andres, Martin; Orfao, Alberto] Univ Salamanca, CSIC, Inst Biol Mol & Celular Canc, Ctr Invest Canc,Lab 11, E-37008 Salamanca, Spain.
[Diaz, David] Univ Salamanca, INCYL, E-37008 Salamanca, Spain.
[Kortum, Robert L.; Samelson, Lawrence E.] NCI, Cellular & Mol Biol Lab, Bethesda, MD 20892 USA.
RP Santos, E (reprint author), Univ Salamanca, CSIC, Inst Biol Mol & Celular Canc, Ctr Invest Canc,Lab 1, E-37008 Salamanca, Spain.
EM esantos@usal.es
OI Diaz, David/0000-0003-3705-817X; Jimeno, David/0000-0001-7876-0083
FU Instituto de Salud Carlos III (Madrid, Spain) [FIS-PS09/01979,
RTICC-RD12/0036/0001, RD12/0036/0048]; Fundacion Samuel Solorzano
(Salamanca, Spain); CCR, NCI, NIH
FX Work was supported by grants FIS-PS09/01979, RTICC-RD12/0036/0001, and
RD12/0036/0048 from Instituto de Salud Carlos III (Madrid, Spain) and
Fundacion Samuel Solorzano (Salamanca, Spain). This research was also
supported by the Intramural Research Program of the CCR, NCI, NIH.
NR 35
TC 5
Z9 5
U1 1
U2 9
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0270-7306
EI 1098-5549
J9 MOL CELL BIOL
JI Mol. Cell. Biol.
PD NOV
PY 2013
VL 33
IS 22
BP 4562
EP 4578
DI 10.1128/MCB.01026-13
PG 17
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 240LX
UT WOS:000326099000017
PM 24043312
ER
PT J
AU Evans, AN
Liu, Y
MacGregor, R
Huang, V
Aguilera, G
AF Evans, Andrew N.
Liu, Ying
MacGregor, Robert
Huang, Victoria
Aguilera, Greti
TI Regulation of Hypothalamic Corticotropin-Releasing Hormone Transcription
by Elevated Glucocorticoids
SO MOLECULAR ENDOCRINOLOGY
LA English
DT Article
ID BINDING PROTEIN-ACTIVITY; SALT-INDUCIBLE KINASE; PARAVENTRICULAR
NUCLEUS; GENE-EXPRESSION; CELL-LINE; MESSENGER-RNA; RECEPTOR; STRESS;
CRH; ACTIVATION
AB Negative glucocorticoid feedback is essential for preventing the deleterious effects of excessive hypothalamic pituitary adrenal axis axis activation, with an important target being CRH transcription in the hypothalamic paraventricular nucleus. The aim of these studies was to determine whether glucocorticoids repress CRH transcription directly in CRH neurons, by examining glucocorticoid effects on glucocorticoid receptor (GR)-CRH promoter interaction and the activation of proteins required for CRH transcription. Immunoprecipitation of hypothalamic chromatin from intact or adrenalectomized rats subjected to either stress or corticosterone injections showed minor association of the proximal CRH promoter with the GR compared with that with phospho-CREB (pCREB). In contrast, the Period-1 (Per1, a glucocorticoid-responsive gene) promoter markedly recruited GR. Stress increased pCREB recruitment by the CRH but not the Per1 promoter, irrespective of circulating glucocorticoids. In vitro, corticosterone pretreatment (30 minutes or 18 hours) only slightly inhibited basal and forskolin-stimulated CRH heteronuclear RNA in primary hypothalamic neuronal cultures and CRH promoter activity in hypothalamic 4B cells. In 4B cells, 30 minutes or 18 hours of corticosterone exposure had no effect on forskolin-induced nuclear accumulation of the recognized CRH transcriptional regulators, pCREB and transducer of regulated CREB activity 2. The data show that inhibition of CRH transcription by physiological glucocorticoids in vitro is minor and that direct interaction of GR with DNA in the proximal CRH promoter may not be a major mechanism of CRH gene repression. Although GR interaction with distal promoter elements may have a role, the data suggest that transcriptional repression of CRH by glucocorticoids involves protein-protein interactions and/or modulation of afferent inputs to the hypothalamic paraventricular nucleus.
C1 [Evans, Andrew N.; Liu, Ying; MacGregor, Robert; Huang, Victoria; Aguilera, Greti] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrine Physiol, Program Dev Endocrinol & Genet, NIH, Bethesda, MD 20892 USA.
RP Aguilera, G (reprint author), NIH, Sect Endocrine Physiol, Eunice Kennedy Shriver Inst Child Hlth & Human De, Bldg 10-CRC,Room 1E-3330, Bethesda, MD 20892 USA.
EM greti_aguilera@nih.gov
OI Evans, Andrew/0000-0002-5366-9942
FU Intramural Research Program, Eunice Kennedy Shriver National Institute
of Child Health and Human Development
FX This work was supported by the Intramural Research Program, Eunice
Kennedy Shriver National Institute of Child Health and Human
Development.
NR 42
TC 15
Z9 16
U1 1
U2 7
PU ENDOCRINE SOC
PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0888-8809
J9 MOL ENDOCRINOL
JI Mol. Endocrinol.
PD NOV
PY 2013
VL 27
IS 11
BP 1796
EP 1807
DI 10.1210/me.2013-1095
PG 12
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 241LL
UT WOS:000326168300003
PM 24065704
ER
PT J
AU Kucka, M
Bjelobaba, I
Clokie, SJH
Klein, DC
Stojilkovic, SS
AF Kucka, Marek
Bjelobaba, Ivana
Clokie, Samuel J. H.
Klein, David C.
Stojilkovic, Stanko S.
TI Female-Specific Induction of Rat Pituitary Dentin Matrix Protein-1 by
GnRH
SO MOLECULAR ENDOCRINOLOGY
LA English
DT Article
ID GONADOTROPIN-RELEASING-HORMONE; SUBUNIT GENE-TRANSCRIPTION;
LUTEINIZING-HORMONE; ANTERIOR-PITUITARY; BETA GENE; L-BETA-T2 CELLS;
IN-VIVO; RNA-SEQ; C-FOS; EXPRESSION
AB Hypothalamic GnRH is the primary regulator of reproduction in vertebrates, acting via the G protein-coupled GnRH receptor (GnRHR) in pituitary gonadotrophs to control synthesis and release of gonadotropins. To identify elements of the GnRHR-coupled gene network, GnRH was applied in a pulsatile manner for 6 hours to a mixed population of perifused pituitary cells from cycling females, mRNA was extracted, and RNA sequencing analysis was performed. This revealed 83 candidate-regulated genes, including a large number coding for secreted proteins. Most notably, GnRH induces a greater than 600-fold increase in expression of dentin matrix protein-1 (Dmp1), one of five members of the small integrin-binding ligand N-linked glycoprotein gene family. The Dmp1 response is mediated by the GnRHR, not elicited by other hypothalamic releasing factors, and is approximately 20-fold smaller in adult male pituitary cells. The sex-dependent Dmp1 response is established during the peripubertal period and independent of the developmental pattern of Gnrhr expression. In vitro, GnRH-induced expression of this gene is coupled with release of DMP1 in extracellular medium through the regulated secretory pathway. In vivo, pituitary Dmp1 expression in identified gonadotrophs is elevated after ovulation. Cell signaling studies revealed that the GnRH induction of Dmp1 is mediated by the protein kinase C signaling pathway and reflects opposing roles of ERK1/2 and p38 MAPK; in addition, the response is facilitated by progesterone. These results establish that DMP1 is a novel secretory protein of female rat gonadotrophs, the synthesis and release of which are controlled by the hypothalamus through the GnRHR signaling pathway. This advance raises intriguing questions about the intrapituitary and downstream effects of this new player in GnRH signaling.
C1 [Kucka, Marek; Bjelobaba, Ivana; Stojilkovic, Stanko S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Sect Cellular Signaling, Bethesda, MD 20892 USA.
[Clokie, Samuel J. H.; Klein, David C.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Sect Neuroendocrinol, Bethesda, MD 20892 USA.
RP Stojilkovic, SS (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bldg 49,Room 6A-36,49 Convent Dr, Bethesda, MD 20892 USA.
EM stojilks@mail.nih.gov
OI Clokie, Samuel/0000-0002-0025-3652
FU Intramural Research Program of the Eunice Kennedy Shriver National
Institute of Child Health and Human Development
FX This work was supported by the Intramural Research Program of the Eunice
Kennedy Shriver National Institute of Child Health and Human
Development.
NR 76
TC 6
Z9 6
U1 1
U2 6
PU ENDOCRINE SOC
PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0888-8809
J9 MOL ENDOCRINOL
JI Mol. Endocrinol.
PD NOV
PY 2013
VL 27
IS 11
BP 1840
EP 1855
DI 10.1210/me.2013-1068
PG 16
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 241LL
UT WOS:000326168300006
PM 24085820
ER
PT J
AU Willer, CJ
Schmidt, EM
Sengupta, S
Peloso, GM
Gustafsson, S
Kanoni, S
Ganna, A
Chen, J
Buchkovich, ML
Mora, S
Beckmann, JS
Bragg-Gresham, JL
Chang, HY
Demirkan, A
Den Hertog, HM
Do, R
Donnelly, LA
Ehret, GB
Esko, T
Feitosa, MF
Ferreira, T
Fischer, K
Fontanillas, P
Fraser, RM
Freitag, DF
Gurdasani, D
Heikkila, K
Hypponen, E
Isaacs, A
Jackson, AU
Johansson, A
Johnson, T
Kaakinen, M
Kettunen, J
Kleber, ME
Li, XH
Luan, JA
Lyytikainen, LP
Magnusson, PKE
Mangino, M
Mihailov, E
Montasser, ME
Muller-Nurasyid, M
Nolte, IM
O'Connell, JR
Palmer, CD
Perola, M
Petersen, AK
Sanna, S
Saxena, R
Service, SK
Shah, S
Shungin, D
Sidore, C
Song, C
Strawbridge, RJ
Surakka, I
Tanaka, T
Teslovich, TM
Thorleifsson, G
Van den Herik, EG
Voight, BF
Volcik, KA
Waite, LL
Wong, A
Wu, Y
Zhang, WH
Absher, D
Asiki, G
Barroso, I
Been, LF
Bolton, JL
Bonnycastle, LL
Brambilla, P
Burnett, MS
Cesana, G
Dimitriou, M
Doney, ASF
Doring, A
Elliott, P
Epstein, SE
Eyjolfsson, GI
Gigante, B
Goodarzi, MO
Grallert, H
Gravito, ML
Groves, CJ
Hallmans, G
Hartikainen, AL
Hayward, C
Hernandez, D
Hicks, AA
Holm, H
Hung, YJ
Illig, T
Jones, MR
Kaleebu, P
Kastelein, JJP
Khaw, KT
Kim, E
Klopp, N
Komulainen, P
Kumari, M
Langenberg, C
Lehtimaki, T
Lin, SY
Lindstrom, J
Loos, RJF
Mach, F
McArdle, WL
Meisinger, C
Mitchell, BD
Muller, G
Nagaraja, R
Narisu, N
Nieminen, TVM
Nsubuga, RN
Olafsson, I
Ong, KK
Palotie, A
Papamarkou, T
Pomilla, C
Pouta, A
Rader, DJ
Reilly, MP
Ridker, PM
Rivadeneira, F
Rudan, I
Ruokonen, A
Samani, N
Scharnagl, H
Seeley, J
Silander, K
Stancakova, A
Stirrups, K
Swift, AJ
Tiret, L
Uitterlinden, AG
van Pelt, LJ
Vedantam, S
Wainwright, N
Wijmenga, C
Wild, SH
Willemsen, G
Wilsgaard, T
Wilson, JF
Young, EH
Zhao, JH
Adair, LS
Arveiler, D
Assimes, TL
Bandinelli, S
Bennett, F
Bochud, M
Boehm, BO
Boomsma, DI
Borecki, IB
Bornstein, SR
Bovet, P
Burnier, M
Campbell, H
Chakravarti, A
Chambers, JC
Chen, YDI
Collins, FS
Cooper, RS
Danesh, J
Dedoussis, G
de Faire, U
Feranil, AB
Ferrieres, J
Ferrucci, L
Freimer, NB
Gieger, C
Groop, LC
Gudnason, V
Gyllensten, U
Hamsten, A
Harris, TB
Hingorani, A
Hirschhorn, JN
Hofman, A
Hovingh, GK
Hsiung, CA
Humphries, SE
Hunt, SC
Hveem, K
Iribarren, C
Jarvelin, MR
Jula, A
Kahonen, M
Kaprio, J
Kesaniemi, A
Kivimaki, M
Kooner, JS
Koudstaal, PJ
Krauss, RM
Kuh, D
Kuusisto, J
Kyvik, KO
Laakso, M
Lakka, TA
Lind, L
Lindgren, CM
Martin, NG
Marz, W
McCarthy, MI
McKenzie, CA
Meneton, P
Metspalu, A
Moilanen, L
Morris, AD
Munroe, PB
Njolstad, I
Pedersen, NL
Power, C
Pramstaller, PP
Price, JF
Psaty, BM
Quertermous, T
Rauramaa, R
Saleheen, D
Salomaa, V
Sanghera, DK
Saramies, J
Schwarz, PEH
Sheu, WHH
Shuldiner, AR
Siegbahn, A
Spector, TD
Stefansson, K
Strachan, DP
Tayo, BO
Tremoli, E
Tuomilehto, J
Uusitupa, M
van Duijn, CM
Vollenweider, P
Wallentin, L
Wareham, NJ
Whitfield, JB
Wolffenbuttel, BHR
Ordovas, JM
Boerwinkle, E
Palmer, CNA
Thorsteinsdottir, U
Chasman, DI
Rotter, JI
Franks, PW
Ripatti, S
Cupples, LA
Sandhu, MS
Rich, SS
Boehnke, M
Deloukas, P
Kathiresan, S
Mohlke, KL
Ingelsson, E
Abecasis, GR
AF Willer, Cristen J.
Schmidt, Ellen M.
Sengupta, Sebanti
Peloso, Gina M.
Gustafsson, Stefan
Kanoni, Stavroula
Ganna, Andrea
Chen, Jin
Buchkovich, Martin L.
Mora, Samia
Beckmann, Jacques S.
Bragg-Gresham, Jennifer L.
Chang, Hsing-Yi
Demirkan, Ayse
Den Hertog, Heleen M.
Do, Ron
Donnelly, Louise A.
Ehret, Georg B.
Esko, Tonu
Feitosa, Mary F.
Ferreira, Teresa
Fischer, Krista
Fontanillas, Pierre
Fraser, Ross M.
Freitag, Daniel F.
Gurdasani, Deepti
Heikkila, Kauko
Hyppoenen, Elina
Isaacs, Aaron
Jackson, Anne U.
Johansson, Asa
Johnson, Toby
Kaakinen, Marika
Kettunen, Johannes
Kleber, Marcus E.
Li, Xiaohui
Luan, Jian'an
Lyytikainen, Leo-Pekka
Magnusson, Patrik K. E.
Mangino, Massimo
Mihailov, Evelin
Montasser, May E.
Mueller-Nurasyid, Martina
Nolte, Ilja M.
O'Connell, Jeffrey R.
Palmer, Cameron D.
Perola, Markus
Petersen, Ann-Kristin
Sanna, Serena
Saxena, Richa
Service, Susan K.
Shah, Sonia
Shungin, Dmitry
Sidore, Carlo
Song, Ci
Strawbridge, Rona J.
Surakka, Ida
Tanaka, Toshiko
Teslovich, Tanya M.
Thorleifsson, Gudmar
Van den Herik, Evita G.
Voight, Benjamin F.
Volcik, Kelly A.
Waite, Lindsay L.
Wong, Andrew
Wu, Ying
Zhang, Weihua
Absher, Devin
Asiki, Gershim
Barroso, Ines
Been, Latonya F.
Bolton, Jennifer L.
Bonnycastle, Lori L.
Brambilla, Paolo
Burnett, Mary S.
Cesana, Giancarlo
Dimitriou, Maria
Doney, Alex S. F.
Doering, Angela
Elliott, Paul
Epstein, Stephen E.
Eyjolfsson, Gudmundur Ingi
Gigante, Bruna
Goodarzi, Mark O.
Grallert, Harald
Gravito, Martha L.
Groves, Christopher J.
Hallmans, Goran
Hartikainen, Anna-Liisa
Hayward, Caroline
Hernandez, Dena
Hicks, Andrew A.
Holm, Hilma
Hung, Yi-Jen
Illig, Thomas
Jones, Michelle R.
Kaleebu, Pontiano
Kastelein, John J. P.
Khaw, Kay-Tee
Kim, Eric
Klopp, Norman
Komulainen, Pirjo
Kumari, Meena
Langenberg, Claudia
Lehtimaki, Terho
Lin, Shih-Yi
Lindstrom, Jaana
Loos, Ruth J. F.
Mach, Francois
McArdle, Wendy L.
Meisinger, Christa
Mitchell, Braxton D.
Mueller, Gabrielle
Nagaraja, Ramaiah
Narisu, Narisu
Nieminen, Tuomo V. M.
Nsubuga, Rebecca N.
Olafsson, Isleifur
Ong, Ken K.
Palotie, Aarno
Papamarkou, Theodore
Pomilla, Cristina
Pouta, Anneli
Rader, Daniel J.
Reilly, Muredach P.
Ridker, Paul M.
Rivadeneira, Fernando
Rudan, Igor
Ruokonen, Aimo
Samani, Nilesh
Scharnagl, Hubert
Seeley, Janet
Silander, Kaisa
Stancakova, Alena
Stirrups, Kathleen
Swift, Amy J.
Tiret, Laurence
Uitterlinden, Andre G.
van Pelt, L. Joost
Vedantam, Sailaja
Wainwright, Nicholas
Wijmenga, Cisca
Wild, Sarah H.
Willemsen, Gonneke
Wilsgaard, Tom
Wilson, James F.
Young, Elizabeth H.
Zhao, Jing Hua
Adair, Linda S.
Arveiler, Dominique
Assimes, Themistocles L.
Bandinelli, Stefania
Bennett, Franklyn
Bochud, Murielle
Boehm, Bernhard O.
Boomsma, Dorret I.
Borecki, Ingrid B.
Bornstein, Stefan R.
Bovet, Pascal
Burnier, Michel
Campbell, Harry
Chakravarti, Aravinda
Chambers, John C.
Chen, Yii-Der Ida
Collins, Francis S.
Cooper, Richard S.
Danesh, John
Dedoussis, George
de Faire, Ulf
Feranil, Alan B.
Ferrieres, Jean
Ferrucci, Luigi
Freimer, Nelson B.
Gieger, Christian
Groop, Leif C.
Gudnason, Vilmundur
Gyllensten, Ulf
Hamsten, Anders
Harris, Tamara B.
Hingorani, Aroon
Hirschhorn, Joel N.
Hofman, Albert
Hovingh, G. Kees
Hsiung, Chao Agnes
Humphries, Steve E.
Hunt, Steven C.
Hveem, Kristian
Iribarren, Carlos
Jarvelin, Marjo-Riitta
Jula, Antti
Kahonen, Mika
Kaprio, Jaakko
Kesaniemi, Antero
Kivimaki, Mika
Kooner, Jaspal S.
Koudstaal, Peter J.
Krauss, Ronald M.
Kuh, Diana
Kuusisto, Johanna
Kyvik, Kirsten O.
Laakso, Markku
Lakka, Timo A.
Lind, Lars
Lindgren, Cecilia M.
Martin, Nicholas G.
Maerz, Winfried
McCarthy, Mark I.
McKenzie, Colin A.
Meneton, Pierre
Metspalu, Andres
Moilanen, Leena
Morris, Andrew D.
Munroe, Patricia B.
Njolstad, Inger
Pedersen, Nancy L.
Power, Chris
Pramstaller, Peter P.
Price, Jackie F.
Psaty, Bruce M.
Quertermous, Thomas
Rauramaa, Rainer
Saleheen, Danish
Salomaa, Veikko
Sanghera, Dharambir K.
Saramies, Jouko
Schwarz, Peter E. H.
Sheu, Wayne H-H
Shuldiner, Alan R.
Siegbahn, Agneta
Spector, Tim D.
Stefansson, Kari
Strachan, David P.
Tayo, Bamidele O.
Tremoli, Elena
Tuomilehto, Jaakko
Uusitupa, Matti
van Duijn, Cornelia M.
Vollenweider, Peter
Wallentin, Lars
Wareham, Nicholas J.
Whitfield, John B.
Wolffenbuttel, Bruce H. R.
Ordovas, Jose M.
Boerwinkle, Eric
Palmer, Colin N. A.
Thorsteinsdottir, Unnur
Chasman, Daniel I.
Rotter, Jerome I.
Franks, Paul W.
Ripatti, Samuli
Cupples, L. Adrienne
Sandhu, Manjinder S.
Rich, Stephen S.
Boehnke, Michael
Deloukas, Panos
Kathiresan, Sekar
Mohlke, Karen L.
Ingelsson, Erik
Abecasis, Goncalo R.
CA Global Lipids Genetics Consortium
TI Discovery and refinement of loci associated with lipid levels
SO NATURE GENETICS
LA English
DT Article
ID CORONARY-ARTERY-DISEASE; DENSITY-LIPOPROTEIN CHOLESTEROL; GENOME-WIDE
ASSOCIATION; HEART-DISEASE; CARDIOVASCULAR-DISEASE; SUSCEPTIBILITY LOCI;
IDENTIFIES 13; RISK; GENE; METAANALYSIS
AB Levels of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides and total cholesterol are heritable, modifiable risk factors for coronary artery disease. To identify new loci and refine known loci influencing these lipids, we examined 188,577 individuals using genome-wide and custom genotyping arrays. We identify and annotate 157 loci associated with lipid levels at P < 5 x 10(-8), including 62 loci not previously associated with lipid levels in humans. Using dense genotyping in individuals of European, East Asian, South Asian and African ancestry, we narrow association signals in 12 loci. We find that loci associated with blood lipid levels are often associated with cardiovascular and metabolic traits, including coronary artery disease, type 2 diabetes, blood pressure, waist-hip ratio and body mass index. Our results demonstrate the value of using genetic data from individuals of diverse ancestry and provide insights into the biological mechanisms regulating blood lipids to guide future genetic, biological and therapeutic research.
C1 [Willer, Cristen J.] Univ Michigan, Dept Internal Med, Div Cardiovasc Med, Ann Arbor, MI 48109 USA.
[Willer, Cristen J.; Schmidt, Ellen M.] Univ Michigan, Dept Computat Med & Bioinformat, Ann Arbor, MI 48109 USA.
[Willer, Cristen J.] Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA.
[Willer, Cristen J.; Sengupta, Sebanti; Chen, Jin; Bragg-Gresham, Jennifer L.; Jackson, Anne U.; Sidore, Carlo; Teslovich, Tanya M.; Boehnke, Michael; Abecasis, Goncalo R.] Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48109 USA.
[Peloso, Gina M.; Cupples, L. Adrienne] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Peloso, Gina M.; Do, Ron; Saxena, Richa; Kathiresan, Sekar] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Peloso, Gina M.; Esko, Tonu; Fontanillas, Pierre; Palmer, Cameron D.; Vedantam, Sailaja; Hirschhorn, Joel N.; Kathiresan, Sekar] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.
[Gustafsson, Stefan; Ganna, Andrea; Song, Ci; Siegbahn, Agneta; Ingelsson, Erik] Uppsala Univ, Dept Med Sci, Uppsala, Sweden.
[Gustafsson, Stefan; Ganna, Andrea; Song, Ci; Ingelsson, Erik] Uppsala Univ, Sci Life Lab, Uppsala, Sweden.
[Kanoni, Stavroula; Gurdasani, Deepti; Barroso, Ines; Papamarkou, Theodore; Pomilla, Cristina; Stirrups, Kathleen; Wainwright, Nicholas; Young, Elizabeth H.; Ripatti, Samuli; Sandhu, Manjinder S.; Deloukas, Panos] Wellcome Trust Sanger Inst, Hinxton, England.
[Ganna, Andrea; Magnusson, Patrik K. E.; Song, Ci; Pedersen, Nancy L.] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
[Buchkovich, Martin L.; Wu, Ying; Mohlke, Karen L.] Univ N Carolina, Dept Genet, Chapel Hill, NC USA.
[Mora, Samia; Ridker, Paul M.; Chasman, Daniel I.] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA.
[Mora, Samia; Ridker, Paul M.; Chasman, Daniel I.] Harvard Univ, Sch Med, Boston, MA USA.
[Beckmann, Jacques S.] Univ Lausanne Hosp, Serv Med Genet, Lausanne, Switzerland.
[Beckmann, Jacques S.] Univ Lausanne, Dept Med Genet, Lausanne, Switzerland.
[Chang, Hsing-Yi] Natl Hlth Res Inst, Inst Populat Hlth Sci, Div Prevent Med & Hlth Serv Res, Zhunan, Taiwan.
[Demirkan, Ayse; Isaacs, Aaron; van Duijn, Cornelia M.] Erasmus Univ, Med Ctr, Dept Epidemiol, Genet Epidemiol Unit, Rotterdam, Netherlands.
[Den Hertog, Heleen M.; Van den Herik, Evita G.; Koudstaal, Peter J.] Erasmus MC, Dept Neurol, Rotterdam, Netherlands.
[Donnelly, Louise A.; Doney, Alex S. F.; Morris, Andrew D.; Palmer, Colin N. A.] Univ Dundee, Ninewells Hosp & Med Sch, Med Res Inst, Dundee DD1 9SY, Scotland.
[Ehret, Georg B.; Mach, Francois] Univ Hosp Geneva, Dept Special Med, Geneva, Switzerland.
[Ehret, Georg B.; Chakravarti, Aravinda] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Ctr Complex Dis Genom, Baltimore, MD USA.
[Esko, Tonu; Fischer, Krista; Mihailov, Evelin; Perola, Markus; Metspalu, Andres] Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia.
[Esko, Tonu; Mihailov, Evelin; Metspalu, Andres] Univ Tartu, Inst Mol & Cell Biol, EE-50090 Tartu, Estonia.
[Feitosa, Mary F.; Borecki, Ingrid B.] Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA.
[Ferreira, Teresa; Lindgren, Cecilia M.; McCarthy, Mark I.; Ingelsson, Erik] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.
[Fraser, Ross M.; Bolton, Jennifer L.; Rudan, Igor; Wild, Sarah H.; Wilson, James F.; Campbell, Harry; Price, Jackie F.] Univ Edinburgh, Ctr Populat Hlth Sci, Edinburgh, Midlothian, Scotland.
[Freitag, Daniel F.; Gurdasani, Deepti; Papamarkou, Theodore; Pomilla, Cristina; Wainwright, Nicholas; Young, Elizabeth H.; Danesh, John; Saleheen, Danish; Sandhu, Manjinder S.] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England.
[Heikkila, Kauko; Kaprio, Jaakko] Univ Helsinki, Dept Publ Hlth, Hjelt Inst, Helsinki, Finland.
[Hyppoenen, Elina; Power, Chris] UCL, Inst Child Hlth, MRC, Ctr Paediat Epidemiol & Biostat,Ctr Epidemiol Chi, London, England.
[Isaacs, Aaron; van Duijn, Cornelia M.] Ctr Med Syst Biol, Leiden, Netherlands.
[Johansson, Asa; Gyllensten, Ulf] Uppsala Univ, Dept Immunol Genet & Pathol, Uppsala, Sweden.
[Johansson, Asa; Siegbahn, Agneta; Wallentin, Lars] Uppsala Univ, Uppsala Clin Res Ctr, Uppsala, Sweden.
[Johnson, Toby; Munroe, Patricia B.] Queen Mary Univ London, Barts & London Sch Med & Dent, Genome Ctr, London, England.
[Johnson, Toby; Munroe, Patricia B.] Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst, Natl Inst Hlth Res,Cardiovasc Biomed Res Unit, London, England.
[Kaakinen, Marika; Jarvelin, Marjo-Riitta] Univ Oulu, Bioctr Oulu, Oulu, Finland.
[Kaakinen, Marika; Elliott, Paul; Jarvelin, Marjo-Riitta] Univ Oulu, Inst Hlth Sci, Oulu, Finland.
[Kettunen, Johannes; Perola, Markus; Surakka, Ida; Palotie, Aarno; Silander, Kaisa; Kaprio, Jaakko; Ripatti, Samuli] Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki, Finland.
[Kettunen, Johannes; Perola, Markus; Surakka, Ida; Silander, Kaisa; Ripatti, Samuli] Natl Inst Hlth & Welf, Publ Hlth Genom Unit, Helsinki, Finland.
[Kleber, Marcus E.] Univ Ulm, Med Ctr, Dept Internal Med Cardiol 2, D-89069 Ulm, Germany.
[Kleber, Marcus E.; Maerz, Winfried] Heidelberg Univ, Med Fac Mannheim, Mannheim Inst Publ Hlth Social & Prevent Med, Mannheim, Germany.
[Li, Xiaohui; Kim, Eric; Rotter, Jerome I.] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA.
[Luan, Jian'an; Langenberg, Claudia; Loos, Ruth J. F.; Ong, Ken K.; Zhao, Jing Hua; Wareham, Nicholas J.] Addenbrookes Hosp, MRC, Inst Metab Sci, Epidemiol Unit, Cambridge, England.
[Lyytikainen, Leo-Pekka; Lehtimaki, Terho] Tampere Univ Hosp, Dept Clin Chem, Fimlab Labs, FIN-33521 Tampere, Finland.
[Lyytikainen, Leo-Pekka; Lehtimaki, Terho] Univ Tampere, Sch Med, Dept Clin Chem, FIN-33101 Tampere, Finland.
[Mangino, Massimo; Spector, Tim D.] Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England.
[Montasser, May E.; O'Connell, Jeffrey R.; Mitchell, Braxton D.; Shuldiner, Alan R.] Univ Maryland, Sch Med, Dept Med, Div Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA.
[Mueller-Nurasyid, Martina; Petersen, Ann-Kristin; Gieger, Christian] Helmholtz Zentrum Munchen, Inst Genet Epidemiol, Neuherberg, Germany.
[Mueller-Nurasyid, Martina] Univ Munich, Univ Hosp Grosshadern, Dept Med 1, Munich, Germany.
[Mueller-Nurasyid, Martina] Univ Munich, Inst Med Informat Biometry & Epidemiol, Munich, Germany.
[Nolte, Ilja M.] Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Groningen, Netherlands.
[Palmer, Cameron D.; Vedantam, Sailaja; Hirschhorn, Joel N.] Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA.
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[Sanna, Serena; Sidore, Carlo] CNR, Ist Ric Genet & Biomed, Monserrato, Italy.
[Service, Susan K.; Freimer, Nelson B.] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Ctr Neurobehav Genet, Los Angeles, CA 90024 USA.
[Shah, Sonia; Kumari, Meena; Hingorani, Aroon; Kivimaki, Mika] UCL, Dept Epidemiol & Publ Hlth, Genet Epidemiol Grp, London, England.
[Shungin, Dmitry; Franks, Paul W.] Lund Univ, Scania Univ Hosp, Ctr Diabet, Dept Clin Sci,Genet & Mol Epidemiol Unit, Malmo, Sweden.
[Shungin, Dmitry] Umea Univ, Dept Odontol, Umea, Sweden.
[Shungin, Dmitry; Franks, Paul W.] Umea Univ, Med Unit, Dept Publ Hlth & Primary Care, Umea, Sweden.
[Sidore, Carlo] Univ Sassari, Dipartimento Sci Biomed, I-07100 Sassari, Italy.
[Strawbridge, Rona J.; Hamsten, Anders] Karolinska Inst, Karolinska Univ Hosp, Dept Med Solna, Atherosclerosis Res Unit, Stockholm, Sweden.
[Strawbridge, Rona J.; Hamsten, Anders] Karolinska Univ Hosp, Ctr Mol Med, Stockholm, Sweden.
[Tanaka, Toshiko; Ferrucci, Luigi] US Natl Inst Hlth, Clin Res Branch, Baltimore, MD USA.
[Thorleifsson, Gudmar; Holm, Hilma; Stefansson, Kari; Thorsteinsdottir, Unnur] deCODE Genet Amgen, Reykjavik, Iceland.
[Voight, Benjamin F.] Univ Penn, Sch Med, Dept Genet, Philadelphia, PA 19104 USA.
[Voight, Benjamin F.] Univ Penn, Sch Med, Dept Syst Pharmacol & Translat Therapeut, Philadelphia, PA 19104 USA.
[Volcik, Kelly A.; Boerwinkle, Eric] Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Ctr Human Genet, Houston, TX 77030 USA.
[Waite, Lindsay L.; Absher, Devin] HudsonAlpha Inst Biotechnol, Huntsville, TX USA.
[Wong, Andrew; Ong, Ken K.; Kuh, Diana] MRC, Unit Lifelong Hlth & Ageing, London, England.
[Zhang, Weihua; Chambers, John C.] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England.
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[Asiki, Gershim; Kaleebu, Pontiano; Nsubuga, Rebecca N.; Seeley, Janet] Uganda Virus Res Inst, MRC, Uganda Res Unit AIDS, Entebbe, Uganda.
[Barroso, Ines] Univ Cambridge, Addenbrookes Hosp, Inst Metab Sci, Metab Res Labs, Cambridge CB2 2QQ, England.
[Barroso, Ines] Addenbrookes Hosp, Inst Metab Sci, NIHR Cambridge Biomed Res Ctr, Cambridge, England.
[Been, Latonya F.; Gravito, Martha L.; Sanghera, Dharambir K.] Univ Oklahoma, Hlth Sci Ctr, Dept Pediat, Oklahoma City, OK 73190 USA.
[Bonnycastle, Lori L.; Narisu, Narisu; Swift, Amy J.; Collins, Francis S.] NHGRI, Genome Technol Branch, US Natl Inst Hlth, Bethesda, MD 20892 USA.
[Brambilla, Paolo] Univ Milano Bicocca, Dept Expt Med, Milan, Italy.
[Burnett, Mary S.; Epstein, Stephen E.] MedStar Hlth Res Inst, Hyattsville, MD USA.
[Cesana, Giancarlo] Univ Milano Bicocca, Res Ctr Publ Hlth, Milan, Italy.
[Dimitriou, Maria; Dedoussis, George] Harokopio Univ, Dept Dietet Nutr, Athens, Greece.
[Doering, Angela; Meisinger, Christa] Helmholtz Zentrum Munchen, Inst Epidemiol 1, Neuherberg, Germany.
[Doering, Angela] Helmholtz Zentrum Munchen, Inst Epidemiol 2, Neuherberg, Germany.
[Elliott, Paul; Jarvelin, Marjo-Riitta] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Ctr Environm & Hlth, Dept Epidemiol & Biostat,MRC,Hlth Protect Agcy, London, England.
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[Goodarzi, Mark O.; Jones, Michelle R.] Cedars Sinai Med Ctr, Dept Med, Div Endocrinol Diabet & Metab, Los Angeles, CA 90048 USA.
[Grallert, Harald; Illig, Thomas; Klopp, Norman] Helmholtz Zentrum Munchen, Res Unit Mol Epidemiol, Neuherberg, Germany.
[Groves, Christopher J.; McCarthy, Mark I.] Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England.
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[Hicks, Andrew A.; Pramstaller, Peter P.] Univ Lubeck, European Acad Bozen Bolzano EURAC, Affiliated Inst, Ctr Biomed, Bolzano, Italy.
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[McArdle, Wendy L.] Univ Bristol, Sch Social & Community Med, Bristol, Avon, England.
[Mueller, Gabrielle] Univ Dresden, Med Fac Carl Gustav Carus, Inst Med Informat & Biometr, Dresden, Germany.
[Nagaraja, Ramaiah] NIA, Genet Lab, Baltimore, MD 21224 USA.
[Nieminen, Tuomo V. M.] Univ Tampere, Sch Med, Dept Clin Pharmacol, FIN-33101 Tampere, Finland.
[Nieminen, Tuomo V. M.] Paijat Hame Cent Hosp, Dept Internal Med, Lahti, Finland.
[Nieminen, Tuomo V. M.] Univ Helsinki, Cent Hosp, Div Cardiol, Helsinki, Finland.
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[Palotie, Aarno] Univ Helsinki, Dept Med Genet, Haartman Inst, Helsinki, Finland.
[Palotie, Aarno] Univ Helsinki, Cent Hosp, Helsinki, Finland.
[Palotie, Aarno] Wellcome Trust Sanger Inst, Genet Epidemiol Grp, Cambridge, England.
[Papamarkou, Theodore] UCL, Dept Stat Sci, London, England.
[Pouta, Anneli; Jarvelin, Marjo-Riitta] Natl Inst Hlth & Welf, Oulu, Finland.
[Rader, Daniel J.; Reilly, Muredach P.] Univ Penn, Perelman Sch Med, Translat Res Ctr, Cardiovasc Inst, Philadelphia, PA 19104 USA.
[Rader, Daniel J.; Reilly, Muredach P.] Univ Penn, Perelman Sch Med, Translat Res Ctr, Div Translat Med & Human Genet, Philadelphia, PA 19104 USA.
[Rivadeneira, Fernando; Uitterlinden, Andre G.; Hofman, Albert] Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands.
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[Rivadeneira, Fernando; Uitterlinden, Andre G.; Hofman, Albert] Netherlands Consortium Hlth Aging, Netherlands Genom Initiat, Leiden, Netherlands.
[Ruokonen, Aimo] Univ Oulu, Dept Clin Sci Clin Chem, Oulu, Finland.
[Samani, Nilesh] Glenfield Hosp, Natl Inst Hlth Res, Leicester Cardiovasc Biomed Res Unit, Leicester, Leics, England.
[Samani, Nilesh] Univ Leicester, Glenfield Hosp, Dept Cardiovasc Sci, Leicester, Leics, England.
[Scharnagl, Hubert; Maerz, Winfried] Med Univ Graz, Clin Inst Med & Chem Lab Diagnost, Graz, Austria.
[Seeley, Janet] Univ E Anglia, Sch Int Dev, Norwich NR4 7TJ, Norfolk, England.
[Stancakova, Alena] Univ Eastern Finland, Dept Med, Kuopio, Finland.
[Stancakova, Alena] Kuopio Univ Hosp, SF-70210 Kuopio, Finland.
[Tiret, Laurence] Univ Paris 06, INSERM, UMRS 937, Paris, France.
[van Pelt, L. Joost] Univ Groningen, Univ Med Ctr Groningen, Dept Lab Med, Groningen, Netherlands.
[van Pelt, L. Joost; Wijmenga, Cisca; Wolffenbuttel, Bruce H. R.] Univ Groningen, Univ Med Ctr Groningen, LifeLines Cohort Study, Groningen, Netherlands.
[Wijmenga, Cisca] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, Groningen, Netherlands.
[Willemsen, Gonneke; Boomsma, Dorret I.] Vrije Univ Amsterdam, Dept Biol Psychol, Amsterdam, Netherlands.
[Wilsgaard, Tom; Njolstad, Inger] Univ Tromso, Fac Hlth Sci, Dept Community Med, Tromso, Norway.
[Adair, Linda S.] Univ N Carolina, Dept Nutr, Chapel Hill, NC USA.
[Arveiler, Dominique] Univ Strasbourg, Fac Med, Dept Epidemiol & Publ Hlth, Strasbourg, France.
[Assimes, Themistocles L.; Quertermous, Thomas] Stanford Univ, Sch Med, Dept Med, Stanford, CA 94305 USA.
[Bandinelli, Stefania] Azienda Sanitaria Firenze, Geriatr Unit, Florence, Italy.
[Bennett, Franklyn] Univ W Indies, Dept Pathol, Mona, Jamaica.
[Bochud, Murielle; Bovet, Pascal] Univ Lausanne Hosp, Inst Social & Prevent Med IUMSP, Lausanne, Switzerland.
[Boehm, Bernhard O.] Univ Ulm, Med Ctr, Dept Internal Med, Div Endocrinol & Diabet, D-89069 Ulm, Germany.
[Boehm, Bernhard O.] Nanyang Technol Univ, Lee Kong Chian Sch Med, Singapore 639798, Singapore.
[Bornstein, Stefan R.; Schwarz, Peter E. H.] Univ Dresden, Med Fac Carl Gustav Carus, Dept Med 3, Dresden, Germany.
[Bovet, Pascal] Minist Hlth, Victoria, Seychelles.
[Burnier, Michel] Univ Lausanne Hosp, Serv Nephrol, Lausanne, Switzerland.
[Chambers, John C.; Kooner, Jaspal S.] Imperial Coll Healthcare Natl Hlth Serv NHS Trust, London, England.
[Chen, Yii-Der Ida] Cedars Sinai Med Ctr, Dept Obstet & Gynecol, Div Reprod Endocrinol, Los Angeles, CA 90048 USA.
[Chen, Yii-Der Ida] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA.
[Cooper, Richard S.; Tayo, Bamidele O.] Loyola Univ, Sch Med, Dept Epidemiol & Prevent Med, Maywood, IL 60153 USA.
[Feranil, Alan B.] Univ San Carlos, Off Populat Studies Fdn, Cebu, Philippines.
[Ferrieres, Jean] Toulouse Univ, Sch Med, Rangueil Hosp, Dept Cardiol, Toulouse, France.
[Freimer, Nelson B.] Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA USA.
[Groop, Leif C.] Lund Univ, Dept Clin Sci, Malmo, Sweden.
[Groop, Leif C.] Helsinki Univ Hosp, Dept Med, Helsinki, Finland.
[Gudnason, Vilmundur] Iceland Heart Assoc, Kopavogur, Iceland.
[Hamsten, Anders] Karolinska Univ Hosp, Dept Cardiol, Stockholm, Sweden.
[Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
[Hsiung, Chao Agnes] Natl Hlth Res Inst, Inst Populat Hlth Sci, Zhunan, Taiwan.
[Humphries, Steve E.] UCL, British Heart Fdn Labs, Inst Cardiovasc Sci, London, England.
[Hunt, Steven C.] Univ Utah, Sch Med, Salt Lake City, UT USA.
[Hveem, Kristian] Norwegian Univ Sci & Technol, Dept Publ Hlth & Gen Practice, Nord Trondelag Hlth Study HUNT Res Ctr, Levanger, Norway.
[Iribarren, Carlos] Kaiser Permanente, Div Res, Oakland, CA USA.
[Jarvelin, Marjo-Riitta] Oulu Univ Hosp, Unit Primary Care, Oulu, Finland.
[Jula, Antti] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Turku, Finland.
[Kahonen, Mika] Univ Tampere, Sch Med, Dept Clin Physiol, FIN-33101 Tampere, Finland.
[Kaprio, Jaakko] Natl Inst Hlth & Welf, Dept Mental Hlth & Subst Abuse Serv, Helsinki, Finland.
[Kesaniemi, Antero] Univ Oulu, Dept Med, Inst Clin Med, Oulu, Finland.
[Kesaniemi, Antero] Oulu Univ Hosp, Clin Res Ctr, Oulu, Finland.
[Kooner, Jaspal S.] Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, Natl Heart & Lung Inst, London, England.
[Krauss, Ronald M.] Childrens Hosp Oakland, Res Inst, Oakland, CA 94609 USA.
[Kuusisto, Johanna; Laakso, Markku] Univ Eastern Finland, Dept Med, Kuopio, Finland.
[Kuusisto, Johanna; Laakso, Markku] Kuopio Univ Hosp, SF-70210 Kuopio, Finland.
[Kyvik, Kirsten O.] Univ Southern Denmark, Inst Reg Hlth Serv Res, Odense, Denmark.
[Kyvik, Kirsten O.] Odense Univ Hosp, Odense Patient Data Explorat Network OPEN, DK-5000 Odense, Denmark.
[Lakka, Timo A.] Univ Eastern Finland, Inst Biomed Physiol, Kuopio, Finland.
[Lind, Lars; Siegbahn, Agneta; Wallentin, Lars] Uppsala Univ, Dept Med Sci, Uppsala, Sweden.
[Martin, Nicholas G.; Whitfield, John B.] Royal Brisbane Hosp, Queensland Inst Med Res, Brisbane, Qld 4029, Australia.
[Maerz, Winfried] Synlab Acad, Synlab Serv, Mannheim, Germany.
[McKenzie, Colin A.] Univ W Indies, Res Inst Trop Med, Trop Metab Res Unit, Mona, Jamaica.
[Meneton, Pierre] Ctr Rech Cordeliers, INSERM U872, Paris, France.
[Moilanen, Leena] Kuopio Univ Hosp, Dept Med, SF-70210 Kuopio, Finland.
[Pramstaller, Peter P.] Gen Cent Hosp, Dept Neurol, Bolzano, Italy.
[Pramstaller, Peter P.] Univ Lubeck, Dept Neurol, Lubeck, Germany.
[Psaty, Bruce M.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA.
[Psaty, Bruce M.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA.
[Psaty, Bruce M.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA.
[Rauramaa, Rainer] Kuopio Univ Hosp, Dept Clin Physiol & Nucl Med, SF-70210 Kuopio, Finland.
[Saleheen, Danish] Ctr Noncommunicable Dis, Karachi, Pakistan.
[Saleheen, Danish] Univ Penn, Dept Med, Philadelphia, PA 19104 USA.
[Salomaa, Veikko] Natl Inst Hlth & Welf, Unit Chron Dis Epidemiol & Prevent, Helsinki, Finland.
[Saramies, Jouko] South Karelia Cent Hosp, Lappeenranta, Finland.
[Schwarz, Peter E. H.] German Ctr Diabet Res DZD, Paul Langerhans Inst Dresden, Dresden, Germany.
[Sheu, Wayne H-H] Taichung Vet Gen Hosp, Div Endocrine & Metab, Dept Internal Med, Taichung, Taiwan.
[Shuldiner, Alan R.] Vet Adm Med Ctr, Geriatr Res & Educ Clin Ctr, Baltimore, MD 21218 USA.
[Stefansson, Kari; Thorsteinsdottir, Unnur] Univ Iceland, Fac Med, Reykjavik, Iceland.
[Strachan, David P.] Univ London, Div Populat Hlth Sci & Educ, London, England.
[Tremoli, Elena] Univ Milan, Monzino Cardiol Ctr, IRCCS, Dept Pharmacol Sci, Milan, Italy.
[Tuomilehto, Jaakko] Danube Univ Krems, Ctr Vasc Prevent, Krems, Austria.
[Tuomilehto, Jaakko] King Abdulaziz Univ, Fac Med, Jeddah 21413, Saudi Arabia.
[Tuomilehto, Jaakko] Hosp Univ La Paz, La Red Temat Invest Cooperat Enfermedades Cardiov, Madrid, Spain.
[Uusitupa, Matti] Univ Eastern Finland, Inst Publ Hlth & Clin Nutr, Kuopio, Finland.
[Uusitupa, Matti] Kuopio Univ Hosp, Res Unit, SF-70210 Kuopio, Finland.
[Vollenweider, Peter] Univ Lausanne Hosp, Dept Med, Lausanne, Switzerland.
[Wolffenbuttel, Bruce H. R.] Univ Groningen, Univ Med Ctr Groningen, Dept Endocrinol, Groningen, Netherlands.
[Ordovas, Jose M.] Natl Ctr Cardiovasc Investigat, Dept Cardiovasc Epidemiol & Populat Genet, Madrid, Spain.
[Ordovas, Jose M.] Inst Madrileno Estudios Avanzados Alimentac, Madrid Inst Adv Studies, Madrid, Spain.
[Ordovas, Jose M.] Tufts Univ, USDA, Human Nutr Res Ctr Aging, Nutr & Genom Lab, Boston, MA 02111 USA.
[Franks, Paul W.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Cupples, L. Adrienne] Framingham Heart Dis Epidemiol Study, Framingham, MA USA.
[Rich, Stephen S.] Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA USA.
[Kathiresan, Sekar] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.
[Kathiresan, Sekar] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
RP Willer, CJ (reprint author), Univ Michigan, Dept Internal Med, Div Cardiovasc Med, Ann Arbor, MI 48109 USA.
EM cristen@umich.edu; mohlke@med.unc.edu; erik.ingelsson@medsci.uu.se;
goncalo@umich.edu
RI Schwarz, Peter/B-5127-2013; Wong, Andrew/M-8899-2016; Magnusson,
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Vilmundur/K-6885-2015; Ripatti, Samuli/H-9446-2014; Wilson, James
F/A-5704-2009; Rivadeneira, Fernando/O-5385-2015; Lyytikainen,
Leo-Pekka/C-8544-2016; Bovet, Pascal/F-4477-2011; Rudan,
Igor/I-1467-2012; Papamarkou, Theodore/A-2958-2012; Kyvik, Kirsten
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mangino, massimo/F-5134-2011; Hayward, Caroline/M-8818-2016; Shah,
Sonia/N-7547-2013; Strawbridge, Rona/H-5422-2012; Boehm,
Bernhard/F-8750-2015; Grallert, Harald/B-3424-2013; Colaus,
PsyColaus/K-6607-2013; Hypponen, Elina/B-2596-2014; Meisinger,
Christine/B-5358-2014; Hsiung, Chao Agnes/E-3994-2010; Wijmenga,
Cisca/D-2173-2009; Chang, Hsing-Yi /E-3973-2010; Palmer,
Colin/C-7053-2008; Pramstaller, Peter/C-2357-2008; Deloukas,
Panos/B-2922-2013
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Martin, Nicholas/0000-0003-4069-8020; Ganna, Andrea/0000-0002-8147-240X;
Nieminen, Tuomo/0000-0003-1755-1688; Meisinger,
Christa/0000-0002-9026-6544; Wolffenbuttel, Bruce
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NR 48
TC 304
Z9 309
U1 9
U2 84
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 2013
VL 45
IS 11
BP 1274
EP +
DI 10.1038/ng.2797
PG 12
WC Genetics & Heredity
SC Genetics & Heredity
GA 244JL
UT WOS:000326384100007
ER
PT J
AU Lessard, CJ
Li, H
Adrianto, I
Ice, JA
Rasmussen, A
Grundahl, KM
Kelly, JA
Dozmorov, MG
Miceli-Richard, C
Bowman, S
Lester, S
Eriksson, P
Eloranta, ML
Brun, JG
Goransson, LG
Harboe, E
Guthridge, JM
Kaufman, KM
Kvarnstrom, M
Jazebi, H
Graham, DSC
Grandits, ME
Nazmul-Hossain, ANM
Patel, K
Adler, AJ
Maier-Moore, JS
Farris, AD
Brennan, MT
Lessard, JA
Chodosh, J
Gopalakrishnan, R
Hefner, KS
Houston, GD
Huang, AJW
Hughes, PJ
Lewis, DM
Radfar, L
Rohrer, MD
Stone, DU
Wren, JD
Vyse, TJ
Gaffney, PM
James, JA
Omdal, R
Wahren-Herlenius, M
Illei, GG
Witte, T
Jonsson, R
Rischmueller, M
Ronnblom, L
Nordmark, G
Ng, WF
Mariette, X
Anaya, JM
Rhodus, NL
Segal, BM
Scofield, RH
Montgomery, CG
Harley, JB
Sivils, KL
AF Lessard, Christopher J.
Li, He
Adrianto, Indra
Ice, John A.
Rasmussen, Astrid
Grundahl, Kiely M.
Kelly, Jennifer A.
Dozmorov, Mikhail G.
Miceli-Richard, Corinne
Bowman, Simon
Lester, Sue
Eriksson, Per
Eloranta, Maija-Leena
Brun, Johan G.
Goransson, Lasse G.
Harboe, Erna
Guthridge, Joel M.
Kaufman, Kenneth M.
Kvarnstrom, Marika
Jazebi, Helmi
Graham, Deborah S. Cunninghame
Grandits, Martha E.
Nazmul-Hossain, Abu N. M.
Patel, Ketan
Adler, Adam J.
Maier-Moore, Jacen S.
Farris, A. Darise
Brennan, Michael T.
Lessard, James A.
Chodosh, James
Gopalakrishnan, Rajaram
Hefner, Kimberly S.
Houston, Glen D.
Huang, Andrew J. W.
Hughes, Pamela J.
Lewis, David M.
Radfar, Lida
Rohrer, Michael D.
Stone, Donald U.
Wren, Jonathan D.
Vyse, Timothy J.
Gaffney, Patrick M.
James, Judith A.
Omdal, Roald
Wahren-Herlenius, Marie
Illei, Gabor G.
Witte, Torsten
Jonsson, Roland
Rischmueller, Maureen
Ronnblom, Lars
Nordmark, Gunnel
Wan-Fai Ng
Mariette, Xavier
Anaya, Juan-Manuel
Rhodus, Nelson L.
Segal, Barbara M.
Scofield, R. Hal
Montgomery, Courtney G.
Harley, John B.
Sivils, Kathy L.
CA UK Primary Sjogren's Syndrome Regi
TI Variants at multiple loci implicated in both innate and adaptive immune
responses are associated with Sjogren's syndrome
SO NATURE GENETICS
LA English
DT Article
ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; GENOME-WIDE ASSOCIATION; PRIMARY
BILIARY-CIRRHOSIS; STRONG RISK-FACTOR; RHEUMATOID-ARTHRITIS;
GENE-EXPRESSION; FUNCTIONAL POLYMORPHISM; SUSCEPTIBILITY LOCI; CLASS-II;
B-CELLS
AB Sjogren's syndrome is a common autoimmune disease (affecting similar to 0.7% of European Americans) that typically presents as keratoconjunctivitis sicca and xerostomia. Here we report results of a large-scale association study of Sjogren's syndrome. In addition to strong association within the human leukocyte antigen (HLA) region at 6p21 (P-meta = 7.65 x 10(-114)), we establish associations with IRF5-TNPO3 (P-meta = 2.73 x 10(-19)), STAT4 (Pmeta = 6.80 x 10-15), IL12A (P-meta = 1.17 x 10(-10)), FAM167ABLK (P-meta = 4.97 x 10(-10)), DDX6-CXCR5 (P-meta = 1.10 x 10(-8)) and TNIP1 (P-meta = 3.30 x 10(-8)). We also observed suggestive associations (P-meta < 5 x 10(-5)) with variants in 29 other regions, including TNFAIP3, PTTG1, PRDM1, DGKQ, FCGR2A, IRAK1BP1, ITSN2 and PHIP, among others. These results highlight the importance of genes that are involved in both innate and adaptive immunity in Sjogren's syndrome.
C1 [Lessard, Christopher J.; Li, He; Adrianto, Indra; Ice, John A.; Rasmussen, Astrid; Grundahl, Kiely M.; Kelly, Jennifer A.; Dozmorov, Mikhail G.; Guthridge, Joel M.; Adler, Adam J.; Maier-Moore, Jacen S.; Farris, A. Darise; Wren, Jonathan D.; Gaffney, Patrick M.; James, Judith A.; Scofield, R. Hal; Montgomery, Courtney G.; Sivils, Kathy L.] Oklahoma Med Res Fdn, Arthrit & Clin Immunol Res Program, Oklahoma City, OK 73104 USA.
[Lessard, Christopher J.; Li, He; James, Judith A.; Sivils, Kathy L.] Univ Oklahoma, Hlth Sci Ctr, Dept Pathol, Oklahoma City, OK USA.
[Miceli-Richard, Corinne; Mariette, Xavier] Univ Paris 11, AP HP, Hop Univ Paris Sud, INSERM,U1012, Paris, France.
[Bowman, Simon] Univ Hosp Birmingham, Dept Rheumatol, Birmingham, W Midlands, England.
[Lester, Sue; Rischmueller, Maureen] Queen Elizabeth Hosp, Dept Rheumatol, Woodville South, SA, Australia.
[Eriksson, Per] Linkoping Univ, Fac Hlth Sci, Dept Rheumatol Clin & Expt Med, Linkoping, Sweden.
[Eloranta, Maija-Leena; Ronnblom, Lars; Nordmark, Gunnel] Uppsala Univ, Dept Med Sci, Rheumatol & Sci Life Lab, Uppsala, Sweden.
[Brun, Johan G.] Univ Bergen, Dept Clin Sci, Rheumatol Sect, Bergen, Norway.
[Brun, Johan G.; Jonsson, Roland] Haukeland Hosp, Dept Rheumatol, N-5021 Bergen, Norway.
[Goransson, Lasse G.; Harboe, Erna; Omdal, Roald] Stavanger Univ Hosp, Dept Internal Med, Clin Immunol Unit, Stavanger, Norway.
[Kaufman, Kenneth M.; Harley, John B.] Cincinnati Childrens Hosp Med Ctr, Div Rheumatol, Cincinnati, OH 45229 USA.
[Kaufman, Kenneth M.; Harley, John B.] Dept Vet Affairs Med Ctr, Cincinnati, OH USA.
[Kvarnstrom, Marika; Jazebi, Helmi; Wahren-Herlenius, Marie] Karolinska Inst, Dept Med, Stockholm, Sweden.
[Jazebi, Helmi] Orebro Univ Hosp, Dept Rheumatol, Orebro, Sweden.
[Graham, Deborah S. Cunninghame; Vyse, Timothy J.] Kings Coll London, Dept Med & Mol Genet, London, England.
[Grandits, Martha E.] United Med Specialties, St Paul, MN USA.
[Nazmul-Hossain, Abu N. M.] Univ Colorado, Sch Dent Med, Denver, CO 80202 USA.
[Patel, Ketan] Univ Minnesota, Sch Dent, Dept Dev & Surg Sci, Div Oral & Maxillofacial Surg, Minneapolis, MN 55455 USA.
[Maier-Moore, Jacen S.; James, Judith A.; Scofield, R. Hal] Univ Oklahoma, Hlth Sci Ctr, Dept Med, Oklahoma City, OK USA.
[Brennan, Michael T.] Carolinas Med Ctr, Dept Oral Med, Charlotte, NC 28203 USA.
[Lessard, James A.] Valley Bone & Joint Clin, Grand Forks, ND USA.
[Chodosh, James] Harvard Univ, Sch Med, Dept Ophthalmol, Massachusetts Eye & Ear Infirm, Boston, MA USA.
[Gopalakrishnan, Rajaram] Univ Minnesota, Sch Dent, Dept Diagnost & Biol Sci, Div Oral & Maxillofacial Pathol, Minneapolis, MN 55455 USA.
[Hefner, Kimberly S.] Hefner Eye Care & Opt Ctr, Oklahoma City, OK USA.
[Houston, Glen D.; Lewis, David M.] Univ Oklahoma, Coll Dent, Dept Oral & Maxillofacial Pathol, Oklahoma City, OK USA.
[Huang, Andrew J. W.] Washington Univ, Dept Ophthalmol & Visual Sci, St Louis, MO 63130 USA.
[Radfar, Lida] Univ Oklahoma, Coll Dent, Oral Diag & Radiol Dept, Oklahoma City, OK USA.
[Rohrer, Michael D.] Univ Minnesota, Sch Dent, Hard Tissue Res Lab, Minneapolis, MN 55455 USA.
[Stone, Donald U.] Univ Oklahoma, Hlth Sci Ctr, Dept Ophthalmol, Oklahoma City, OK USA.
[Wren, Jonathan D.] Univ Oklahoma, Hlth Sci Ctr, Dept Biochem & Mol Biol, Oklahoma City, OK 73190 USA.
[Illei, Gabor G.] Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA.
[Witte, Torsten] Hannover Med Sch, Dept Clin Immunol & Rheumatol, Hannover, Germany.
[Jonsson, Roland] Univ Bergen, Dept Clin Sci, Broegelmann Res Lab, Bergen, Norway.
[Rischmueller, Maureen] Univ Adelaide, Queen Elizabeth Hosp, Dept Rheumatol, Adelaide, SA 5005, Australia.
[Rischmueller, Maureen] Univ Adelaide, Discipline Med, Adelaide, SA 5005, Australia.
[Wan-Fai Ng] Newcastle Univ, Inst Cellular Med, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England.
[Anaya, Juan-Manuel] Univ Rosario, Ctr Autoimmune Dis Res CREA, Bogota, Colombia.
[Rhodus, Nelson L.] Univ Minnesota, Sch Dent, Dept Oral Surg, Minneapolis, MN 55455 USA.
[Segal, Barbara M.] Univ Minnesota, Sch Med, Div Rheumatol, Minneapolis, MN 55455 USA.
[Scofield, R. Hal] Dept Vet Affairs Med Ctr, Oklahoma City, OK USA.
RP Sivils, KL (reprint author), Oklahoma Med Res Fdn, Arthrit & Clin Immunol Res Program, 825 NE 13th St, Oklahoma City, OK 73104 USA.
EM sivilsk@omrf.org
RI Witte, Torsten/B-5783-2016; Anaya, Juan-Manuel/J-1960-2016;
OI Anaya, Juan-Manuel/0000-0002-6444-1249; Universidad del Rosario,
Biblioteca/0000-0003-3491-9392; Dozmorov, Mikhail/0000-0002-0086-8358;
Houston, Graeme/0000-0002-9786-7975; Adrianto,
Indra/0000-0002-9973-3057; Wahren-Herlenius, Marie/0000-0002-0915-7245;
Huang, Andrew JW/0000-0003-1939-9149
FU NIH [P50 AR0608040, 5P01 AR049084-10, 5P30 AR053483, 1U01 AI101934, 5P30
GM103510]; Intramural Research Program of the National Institute of
Dental and Craniofacial Research; American College of Rheumatology
Research and Education Foundation/Abbott Health Professional Graduate
Student Preceptorship Award
FX We thank the following funding agencies for their support: this
publication was made possible by grants P50 AR0608040 (K. L. S., C. J.
L., R. H. S. and A. D. F.), 5R01 DE015223 (K. L. S. and J. B. H.), 5RC2
AR058959 (P. M. G.), 5P01 AR049084-10 (J. B. H.), 5P30 AR053483 (J. A.
J. and J. M. G.), 5U19 AI082714 (K. L. S., J. A. J. and C. J. L.), 1R01
DE018209-02 (K. L. S. and J. B. H.), 5R01 DE018209 (K. L. S.), 8P20
GM103456 (P. M. G., C. J. L., J. D. W. and I. A.), P20 GM103636 (M. G.
D. and J. D. W.), 5R37 AI024717-25 (J. B. H.), 5P01 AI083194-03 (K. L.
S. and J. B. H.), 7S10 RR027190-02 (J. B. H.), 1U01 AI101934 (J. A. J.
and J. M. G.), 1RC1 AR058554 (J. A. J. and J. M. G.) and 5P30 GM103510
(J. A. J. and J. M. G.) from the NIH. The contents are the sole
responsibility of the authors and do not necessarily represent the
official views of the NIH. Additional funding was obtained from
Intramural Research Program of the National Institute of Dental and
Craniofacial Research (G. G. I.), US Department of Veterans Affairs IMMA
9 (J. B. H.), US Department of Defense PR094002 (J. B. H.), American
College of Rheumatology Research and Education Foundation/Abbott Health
Professional Graduate Student Preceptorship Award 2009 (C. J. L. and K.
L. S.), Oklahoma Medical Research Foundation (C. J. L. and K. L. S.),
Sjogren's Syndrome Foundation (K. L. S.), Phileona Foundation (K. L.
S.), the French ministry of health (PHRC 2006-AOM06133) and the French
ministry of research (ANR-2010-BLAN-1133) (X. M. and C. M.-R.), The
Strategic Research Program at Helse Bergen, Western Norway Regional
Health Authority (L. G. G., J. G. B. and R. J.), The Broegelmann
Foundation (J. G. B. and R. J.), Norwegian Foundation for Health and
Rehabilitation (E. H.), KFO 250 TP03, WI 1031/6-1 (T. W.), KFO 250, Z1
(T. W.), Medical Research Council, UK G0800629 (W.-F. N. and S. B.),
Northumberland, Tyne and Wear Comprehensive Local Research Network
(CLRN) (W.-F. N.), The Swedish Research Council (M. W.-H. and L.
R~nnblom), The King Gustaf the V-th 80-year Foundation (M. W.-H.), Knut
and Alice Wallenberg Foundation (L. Ronnblom) and The Swedish Rheumatism
Association (M. W.-H., G. N., L. Ronnblom and P. E.). This study made
use of genotypes available through dbGAP, with acknowledgments provided
in the Supplementary Note.
NR 84
TC 97
Z9 99
U1 3
U2 19
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 2013
VL 45
IS 11
BP 1284
EP +
DI 10.1038/ng.2792
PG 11
WC Genetics & Heredity
SC Genetics & Heredity
GA 244JL
UT WOS:000326384100008
PM 24097067
ER
PT J
AU Do, R
Willer, CJ
Schmidt, EM
Sengupta, S
Gao, C
Peloso, GM
Gustafsson, S
Kanoni, S
Ganna, A
Chen, J
Buchkovich, ML
Mora, S
Beckmann, JS
Bragg-Gresham, JL
Chang, HY
Demirkan, A
Den Hertog, HM
Donnelly, LA
Ehret, GB
Esko, T
Feitosa, MF
Ferreira, T
Fischer, K
Fontanillas, P
Fraser, RM
Freitag, DF
Gurdasani, D
Heikkila, K
Hypponen, E
Isaacs, A
Jackson, AU
Johansson, A
Johnson, T
Kaakinen, M
Kettunen, J
Kleber, ME
Li, XH
Luan, JA
Lyytikainen, LP
Magnusson, PKE
Mangino, M
Mihailov, E
Montasser, ME
Muller-Nurasyid, M
Nolte, IM
O'Connell, JR
Palmer, CD
Perola, M
Petersen, AK
Sanna, S
Saxena, R
Service, SK
Shah, S
Shungin, D
Sidore, C
Song, C
Strawbridge, RJ
Surakka, I
Tanaka, T
Teslovich, TM
Thorleifsson, G
Van den Herik, EG
Voight, BF
Volcik, KA
Waite, LL
Wong, A
Wu, Y
Zhang, WH
Absher, D
Asiki, G
Barroso, I
Been, LF
Bolton, JL
Bonnycastle, LL
Brambilla, P
Burnett, MS
Cesana, G
Dimitriou, M
Doney, ASF
Doring, A
Elliott, P
Epstein, SE
Eyjolfsson, GI
Gigante, B
Goodarzi, MO
Grallert, H
Gravito, ML
Groves, CJ
Hallmans, G
Hartikainen, AL
Hayward, C
Hernandez, D
Hicks, AA
Holm, H
Hung, YJ
Illig, T
Jones, MR
Kaleebu, P
Kastelein, JJP
Khaw, KT
Kim, E
Klopp, N
Komulainen, P
Kumari, M
Langenberg, C
Lehtimaki, T
Lin, SY
Lindstrom, J
Loos, RJF
Mach, F
McArdle, WL
Meisinger, C
Mitchell, BD
Muller, G
Nagaraja, R
Narisu, N
Nieminen, TVM
Nsubuga, RN
Olafsson, I
Ong, KK
Palotie, A
Papamarkou, T
Pomilla, C
Pouta, A
Rader, DJ
Reilly, MP
Ridker, PM
Rivadeneira, F
Rudan, I
Ruokonen, A
Samani, N
Scharnagl, H
Seeley, J
Silander, K
Stancakova, A
Stirrups, K
Swift, AJ
Tiret, L
Uitterlinden, AG
van Pelt, LJ
Vedantam, S
Wainwright, N
Wijmenga, C
Wild, SH
Willemsen, G
Wilsgaard, T
Wilson, JF
Young, EH
Zhao, JH
Adair, LS
Arveiler, D
Assimes, TL
Bandinelli, S
Bennett, F
Bochud, M
Boehm, BO
Boomsma, DI
Borecki, IB
Bornstein, SR
Bovet, P
Burnier, M
Campbell, H
Chakravarti, A
Chambers, JC
Chen, YDI
Collins, FS
Cooper, RS
Danesh, J
Dedoussis, G
de Faire, U
Feranil, AB
Ferrieres, J
Ferrucci, L
Freimer, NB
Gieger, C
Groop, LC
Gudnason, V
Gyllensten, U
Hamsten, A
Harris, TB
Hingorani, A
Hirschhorn, JN
Hofman, A
Hovingh, GK
Hsiung, CA
Humphries, SE
Hunt, SC
Hveem, K
Iribarren, C
Jarvelin, MR
Jula, A
Kahonen, M
Kaprio, J
Kesaniemi, A
Kivimaki, M
Kooner, JS
Koudstaal, PJ
Krauss, RM
Kuh, D
Kuusisto, J
Kyvik, KO
Laakso, M
Lakka, TA
Lind, L
Lindgren, CM
Martin, NG
Marz, W
McCarthy, MI
McKenzie, CA
Meneton, P
Metspalu, A
Moilanen, L
Morris, AD
Munroe, PB
Njolstad, I
Pedersen, NL
Power, C
Pramstaller, PP
Price, JF
Psaty, BM
Quertermous, T
Rauramaa, R
Saleheen, D
Salomaa, V
Sanghera, DK
Saramies, J
Schwarz, PEH
Sheu, WHH
Shuldiner, AR
Siegbahn, A
Spector, TD
Stefansson, K
Strachan, DP
Tayo, BO
Tremoli, E
Tuomilehto, J
Uusitupa, M
van Duijn, CM
Vollenweider, P
Wallentin, L
Wareham, NJ
Whitfield, JB
Wolffenbuttel, BHR
Altshuler, D
Ordovas, JM
Boerwinkle, E
Palmer, CNA
Thorsteinsdottir, U
Chasman, DI
Rotter, JI
Franks, PW
Ripatti, S
Cupples, LA
Sandhu, MS
Rich, SS
Boehnke, M
Deloukas, P
Mohlke, KL
Ingelsson, E
Abecasis, GR
Daly, MJ
Neale, BM
Kathiresan, S
AF Do, Ron
Willer, Cristen J.
Schmidt, Ellen M.
Sengupta, Sebanti
Gao, Chi
Peloso, Gina M.
Gustafsson, Stefan
Kanoni, Stavroula
Ganna, Andrea
Chen, Jin
Buchkovich, Martin L.
Mora, Samia
Beckmann, Jacques S.
Bragg-Gresham, Jennifer L.
Chang, Hsing-Yi
Demirkan, Ayse
Den Hertog, Heleen M.
Donnelly, Louise A.
Ehret, Georg B.
Esko, Tonu
Feitosa, Mary F.
Ferreira, Teresa
Fischer, Krista
Fontanillas, Pierre
Fraser, Ross M.
Freitag, Daniel F.
Gurdasani, Deepti
Heikkila, Kauko
Hyppoenen, Elina
Isaacs, Aaron
Jackson, Anne U.
Johansson, Asa
Johnson, Toby
Kaakinen, Marika
Kettunen, Johannes
Kleber, Marcus E.
Li, Xiaohui
Luan, Jian'an
Lyytikainen, Leo-Pekka
Magnusson, Patrik K. E.
Mangino, Massimo
Mihailov, Evelin
Montasser, May E.
Mueller-Nurasyid, Martina
Nolte, Ilja M.
O'Connell, Jeffrey R.
Palmer, Cameron D.
Perola, Markus
Petersen, Ann-Kristin
Sanna, Serena
Saxena, Richa
Service, Susan K.
Shah, Sonia
Shungin, Dmitry
Sidore, Carlo
Song, Ci
Strawbridge, Rona J.
Surakka, Ida
Tanaka, Toshiko
Teslovich, Tanya M.
Thorleifsson, Gudmar
Van den Herik, Evita G.
Voight, Benjamin F.
Volcik, Kelly A.
Waite, Lindsay L.
Wong, Andrew
Wu, Ying
Zhang, Weihua
Absher, Devin
Asiki, Gershim
Barroso, Ines
Been, Latonya F.
Bolton, Jennifer L.
Bonnycastle, Lori L.
Brambilla, Paolo
Burnett, Mary S.
Cesana, Giancarlo
Dimitriou, Maria
Doney, Alex S. F.
Doering, Angela
Elliott, Paul
Epstein, Stephen E.
Eyjolfsson, Gudmundur Ingi
Gigante, Bruna
Goodarzi, Mark O.
Grallert, Harald
Gravito, Martha L.
Groves, Christopher J.
Hallmans, Goran
Hartikainen, Anna-Liisa
Hayward, Caroline
Hernandez, Dena
Hicks, Andrew A.
Holm, Hilma
Hung, Yi-Jen
Illig, Thomas
Jones, Michelle R.
Kaleebu, Pontiano
Kastelein, John J. P.
Khaw, Kay-Tee
Kim, Eric
Klopp, Norman
Komulainen, Pirjo
Kumari, Meena
Langenberg, Claudia
Lehtimaki, Terho
Lin, Shih-Yi
Lindstrom, Jaana
Loos, Ruth J. F.
Mach, Francois
McArdle, Wendy L.
Meisinger, Christa
Mitchell, Braxton D.
Mueller, Gabrielle
Nagaraja, Ramaiah
Narisu, Narisu
Nieminen, Tuomo V. M.
Nsubuga, Rebecca N.
Olafsson, Isleifur
Ong, Ken K.
Palotie, Aarno
Papamarkou, Theodore
Pomilla, Cristina
Pouta, Anneli
Rader, Daniel J.
Reilly, Muredach P.
Ridker, Paul M.
Rivadeneira, Fernando
Rudan, Igor
Ruokonen, Aimo
Samani, Nilesh
Scharnagl, Hubert
Seeley, Janet
Silander, Kaisa
Stancakova, Alena
Stirrups, Kathleen
Swift, Amy J.
Tiret, Laurence
Uitterlinden, Andre G.
van Pelt, L. Joost
Vedantam, Sailaja
Wainwright, Nicholas
Wijmenga, Cisca
Wild, Sarah H.
Willemsen, Gonneke
Wilsgaard, Tom
Wilson, James F.
Young, Elizabeth H.
Zhao, Jing Hua
Adair, Linda S.
Arveiler, Dominique
Assimes, Themistocles L.
Bandinelli, Stefania
Bennett, Franklyn
Bochud, Murielle
Boehm, Bernhard O.
Boomsma, Dorret I.
Borecki, Ingrid B.
Bornstein, Stefan R.
Bovet, Pascal
Burnier, Michel
Campbell, Harry
Chakravarti, Aravinda
Chambers, John C.
Chen, Yii-Der Ida
Collins, Francis S.
Cooper, Richard S.
Danesh, John
Dedoussis, George
de Faire, Ulf
Feranil, Alan B.
Ferrieres, Jean
Ferrucci, Luigi
Freimer, Nelson B.
Gieger, Christian
Groop, Leif C.
Gudnason, Vilmundur
Gyllensten, Ulf
Hamsten, Anders
Harris, Tamara B.
Hingorani, Aroon
Hirschhorn, Joel N.
Hofman, Albert
Hovingh, G. Kees
Hsiung, Chao Agnes
Humphries, Steve E.
Hunt, Steven C.
Hveem, Kristian
Iribarren, Carlos
Jarvelin, Marjo-Riitta
Jula, Antti
Kahonen, Mika
Kaprio, Jaakko
Kesaniemi, Antero
Kivimaki, Mika
Kooner, Jaspal S.
Koudstaal, Peter J.
Krauss, Ronald M.
Kuh, Diana
Kuusisto, Johanna
Kyvik, Kirsten O.
Laakso, Markku
Lakka, Timo A.
Lind, Lars
Lindgren, Cecilia M.
Martin, Nicholas G.
Maerz, Winfried
McCarthy, Mark I.
McKenzie, Colin A.
Meneton, Pierre
Metspalu, Andres
Moilanen, Leena
Morris, Andrew D.
Munroe, Patricia B.
Njolstad, Inger
Pedersen, Nancy L.
Power, Chris
Pramstaller, Peter P.
Price, Jackie F.
Psaty, Bruce M.
Quertermous, Thomas
Rauramaa, Rainer
Saleheen, Danish
Salomaa, Veikko
Sanghera, Dharambir K.
Saramies, Jouko
Schwarz, Peter E. H.
Sheu, Wayne H-H
Shuldiner, Alan R.
Siegbahn, Agneta
Spector, Tim D.
Stefansson, Kari
Strachan, David P.
Tayo, Bamidele O.
Tremoli, Elena
Tuomilehto, Jaakko
Uusitupa, Matti
van Duijn, Cornelia M.
Vollenweider, Peter
Wallentin, Lars
Wareham, Nicholas J.
Whitfield, John B.
Wolffenbuttel, Bruce H. R.
Altshuler, David
Ordovas, Jose M.
Boerwinkle, Eric
Palmer, Colin N. A.
Thorsteinsdottir, Unnur
Chasman, Daniel I.
Rotter, Jerome I.
Franks, Paul W.
Ripatti, Samuli
Cupples, L. Adrienne
Sandhu, Manjinder S.
Rich, Stephen S.
Boehnke, Michael
Deloukas, Panos
Mohlke, Karen L.
Ingelsson, Erik
Abecasis, Goncalo R.
Daly, Mark J.
Neale, Benjamin M.
Kathiresan, Sekar
TI Common variants associated with plasma triglycerides and risk for
coronary artery disease
SO NATURE GENETICS
LA English
DT Article
ID HIGH-DENSITY-LIPOPROTEIN; ISCHEMIC-HEART-DISEASE; TYPE-2
DIABETES-MELLITUS; MENDELIAN RANDOMIZATION; CARDIOVASCULAR-DISEASE;
GENETIC EPIDEMIOLOGY; CHOLESTEROL LEVELS; LOCI; CONTRIBUTE; THERAPY
AB Triglycerides are transported in plasma by specific triglyceride-rich lipoproteins; in epidemiological studies, increased triglyceride levels correlate with higher risk for coronary artery disease (CAD). However, it is unclear whether this association reflects causal processes. We used 185 common variants recently mapped for plasma lipids (P < 5 x 10(-8) for each) to examine the role of triglycerides in risk for CAD. First, we highlight loci associated with both low-density lipoprotein cholesterol (LDL-C) and triglyceride levels, and we show that the direction and magnitude of the associations with both traits are factors in determining CAD risk. Second, we consider loci with only a strong association with triglycerides and show that these loci are also associated with CAD. Finally, in a model accounting for effects on LDL-C and/or high-density lipoprotein cholesterol (HDL-C) levels, the strength of a polymorphism's effect on triglyceride levels is correlated with the magnitude of its effect on CAD risk. These results suggest that triglyceride-rich lipoproteins causally influence risk for CAD.
C1 Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.
Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.
Univ Michigan, Dept Internal Med, Div Cardiovasc Med, Ann Arbor, MI 48109 USA.
Univ Michigan, Dept Computat Med & Bioinformat, Ann Arbor, MI 48109 USA.
Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA.
Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48109 USA.
Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
Uppsala Univ, Dept Med Sci, Uppsala, Sweden.
Uppsala Univ, Sci Life Lab, Uppsala, Sweden.
Wellcome Trust Sanger Inst, Cambridge, England.
Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
Univ N Carolina, Dept Genet, Chapel Hill, NC USA.
Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA.
Brigham & Womens Hosp, Dept Med, Div Cardiovasc Med, Boston, MA 02115 USA.
Harvard Univ, Sch Med, Boston, MA USA.
Univ Lausanne Hosp, Serv Med Genet, Lausanne, Switzerland.
Univ Lausanne, Dept Med Genet, Lausanne, Switzerland.
Natl Hlth Res Inst, Inst Populat Hlth Sci, Div Prevent Med & Hlth Serv Res, Zhunan, Taiwan.
Erasmus Univ, Med Ctr, Dept Epidemiol, Genet Epidemiol Unit, Rotterdam, Netherlands.
[Den Hertog, Heleen M.; Van den Herik, Evita G.; Koudstaal, Peter J.] Erasmus MC, Dept Neurol, Rotterdam, Netherlands.
[Donnelly, Louise A.; Doney, Alex S. F.; Morris, Andrew D.; Palmer, Colin N. A.] Univ Dundee, Ninewells Hosp, Med Res Inst, Dundee, Scotland.
[Donnelly, Louise A.; Doney, Alex S. F.; Morris, Andrew D.; Palmer, Colin N. A.] Sch Med, Dundee, Scotland.
[Ehret, Georg B.; Mach, Francois] Univ Hosp Geneva, Dept Special Med, Geneva, Switzerland.
[Ehret, Georg B.; Chakravarti, Aravinda] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Ctr Complex Dis Genom, Baltimore, MD USA.
[Esko, Tonu; Fischer, Krista; Mihailov, Evelin; Perola, Markus; Metspalu, Andres] Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia.
[Esko, Tonu; Mihailov, Evelin; Metspalu, Andres] Univ Tartu, Inst Mol & Cell Biol, EE-50090 Tartu, Estonia.
[Feitosa, Mary F.; Borecki, Ingrid B.] Washington Univ, Sch Med, Dept Genet, St Louis, MO 63110 USA.
[Ferreira, Teresa; Lindgren, Cecilia M.; McCarthy, Mark I.; Ingelsson, Erik] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.
[Fraser, Ross M.; Bolton, Jennifer L.; Rudan, Igor; Wild, Sarah H.; Wilson, James F.; Campbell, Harry; Price, Jackie F.] Univ Edinburgh, Ctr Populat Hlth Sci, Edinburgh, Midlothian, Scotland.
[Freitag, Daniel F.; Gurdasani, Deepti; Papamarkou, Theodore; Pomilla, Cristina; Wainwright, Nicholas; Young, Elizabeth H.; Danesh, John; Saleheen, Danish; Sandhu, Manjinder S.] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England.
[Heikkila, Kauko; Kaprio, Jaakko] Univ Helsinki, Dept Publ Hlth, Hjelt Inst, Helsinki, Finland.
[Hyppoenen, Elina; Power, Chris] UCL, Inst Child Hlth, MRC, Ctr Paediat Epidemiol & Biostat,Ctr Epidemiol Chi, London, England.
[Isaacs, Aaron; van Duijn, Cornelia M.] Ctr Med Syst Biol, Leiden, Netherlands.
[Johansson, Asa; Gyllensten, Ulf] Uppsala Univ, Dept Immunol Genet & Pathol, Uppsala, Sweden.
[Johansson, Asa; Siegbahn, Agneta; Wallentin, Lars] Uppsala Univ, Uppsala Clin Res Ctr, Uppsala, Sweden.
[Johnson, Toby; Munroe, Patricia B.] Queen Mary Univ London, Barts & London Sch Med & Dent, Genome Ctr, London, England.
[Johnson, Toby; Munroe, Patricia B.] Queen Mary Univ London, Barts & London Sch Med & Dent, William Harvey Res Inst,Natl Inst Hlth Res, Cardiovasc Biomed Res Unit, London, England.
[Kaakinen, Marika; Jarvelin, Marjo-Riitta] Univ Oulu, Bioctr Oulu, Oulu, Finland.
[Kaakinen, Marika; Elliott, Paul; Jarvelin, Marjo-Riitta] Univ Oulu, Inst Hlth Sci, Oulu, Finland.
[Kettunen, Johannes; Perola, Markus; Surakka, Ida; Silander, Kaisa; Ripatti, Samuli] Univ Helsinki, Inst Mol Med Finland FIMM, Helsinki, Finland.
[Kettunen, Johannes; Perola, Markus; Surakka, Ida; Silander, Kaisa; Ripatti, Samuli] Natl Inst Hlth & Welf, Publ Hlth Genom Unit, Helsinki, Finland.
[Kleber, Marcus E.] Univ Ulm, Med Ctr, Dept Internal Med Cardiol 2, D-89069 Ulm, Germany.
[Kleber, Marcus E.; Maerz, Winfried] Heidelberg Univ, Med Fac Mannheim, Mannheim Inst Publ Hlth Social & Prevent Med, Mannheim, Germany.
[Li, Xiaohui; Kim, Eric; Rotter, Jerome I.] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA.
[Luan, Jian'an; Langenberg, Claudia; Loos, Ruth J. F.; Ong, Ken K.; Zhao, Jing Hua; Wareham, Nicholas J.] Addenbrookes Hosp, Inst Metab Sci, Epidemiol Unit, MRC, Cambridge, England.
[Lyytikainen, Leo-Pekka; Lehtimaki, Terho] Tampere Univ Hosp, Dept Clin Chem, Fimlab Labs, FIN-33521 Tampere, Finland.
[Lyytikainen, Leo-Pekka; Lehtimaki, Terho] Univ Tampere, Sch Med, Dept Clin Chem, FIN-33101 Tampere, Finland.
[Mangino, Massimo; Spector, Tim D.] Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England.
[Montasser, May E.; O'Connell, Jeffrey R.; Mitchell, Braxton D.; Shuldiner, Alan R.] Univ Maryland, Sch Med, Dept Med, Div Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA.
[Mueller-Nurasyid, Martina; Petersen, Ann-Kristin; Gieger, Christian] Helmholtz Zentrum Munchen, Inst Genet Epidemiol, Neuherberg, Germany.
[Mueller-Nurasyid, Martina] Univ Munich, Univ Hosp Grosshadern, Dept Med 1, Munich, Germany.
[Mueller-Nurasyid, Martina] Univ Munich, Inst Med Informat Biometry & Epidemiol, Munich, Germany.
[Nolte, Ilja M.] Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, Groningen, Netherlands.
[Palmer, Cameron D.; Vedantam, Sailaja; Hirschhorn, Joel N.] Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA.
[Palmer, Cameron D.; Vedantam, Sailaja; Hirschhorn, Joel N.] Childrens Hosp, Div Genet, Program Genom, Boston, MA 02115 USA.
[Sanna, Serena; Sidore, Carlo] CNR, Ist Ric Genet & Biomed, Monserrato, Italy.
[Service, Susan K.; Freimer, Nelson B.] Univ Calif Los Angeles, Semel Inst Neurosci & Human Behav, Ctr Neurobehav Genet, Los Angeles, CA 90024 USA.
[Shah, Sonia; Kumari, Meena; Hingorani, Aroon; Kivimaki, Mika] UCL, Dept Epidemiol & Publ Hlth, Genet Epidemiol Grp, London, England.
[Shungin, Dmitry; Franks, Paul W.] Lund Univ, Ctr Diabet, Scania Univ Hosp, Dept Clin Sci,Genet & Mol Epidemiol Unit, Malmo, Sweden.
[Shungin, Dmitry] Umea Univ, Dept Odontol, Umea, Sweden.
[Shungin, Dmitry; Franks, Paul W.] Umea Univ, Dept Publ Hlth & Primary Care, Med Unit, Umea, Sweden.
[Sidore, Carlo] Univ Sassari, Dipartimento Sci Biomed, I-07100 Sassari, Italy.
[Strawbridge, Rona J.; Hamsten, Anders] Karolinska Univ Hosp, Karolinska Inst, Dept Med Solna, Atherosclerosis Res Unit, Stockholm, Sweden.
[Strawbridge, Rona J.; Hamsten, Anders] Karolinska Univ Hosp, Ctr Mol Med, Stockholm, Sweden.
[Tanaka, Toshiko; Ferrucci, Luigi] NIH, Clin Res Branch, Baltimore, MD USA.
[Thorleifsson, Gudmar; Holm, Hilma; Stefansson, Kari; Thorsteinsdottir, Unnur] deCODE Genet Amgen, Reykjavik, Iceland.
[Voight, Benjamin F.] Univ Penn, Sch Med, Dept Genet, Philadelphia, PA 19104 USA.
[Voight, Benjamin F.] Univ Penn, Sch Med, Dept Syst Pharmacol & Translat Therapeut, Philadelphia, PA 19104 USA.
[Volcik, Kelly A.; Boerwinkle, Eric] Univ Texas Hlth Sci Ctr Houston, Sch Publ Hlth, Ctr Human Genet, Houston, TX 77030 USA.
[Waite, Lindsay L.; Absher, Devin] HudsonAlpha Inst Biotechnol, Huntsville, TX USA.
[Wong, Andrew; Ong, Ken K.; Kuh, Diana] MRC, Unit Lifelong Hlth & Ageing, London, England.
[Zhang, Weihua; Elliott, Paul; Chambers, John C.; Jarvelin, Marjo-Riitta] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Epidemiol & Biostat, London, England.
[Asiki, Gershim; Kaleebu, Pontiano; Nsubuga, Rebecca N.; Seeley, Janet] Uganda Virus Res Inst, MRC, Uganda Res Unit AIDS, Entebbe, Uganda.
[Barroso, Ines] Univ Cambridge, Addenbrookes Hosp, Inst Metab Sci, Metab Res Labs, Cambridge CB2 2QQ, England.
[Barroso, Ines] Addenbrookes Hosp, Inst Metab Sci, NIHR Cambridge Biomed Res Ctr, Cambridge, England.
[Been, Latonya F.; Gravito, Martha L.; Sanghera, Dharambir K.] Univ Oklahoma, Hlth Sci Ctr, Dept Pediat, Oklahoma City, OK 73190 USA.
[Bonnycastle, Lori L.; Narisu, Narisu; Swift, Amy J.; Collins, Francis S.] NHGRI, NIH, Genome Technol Branch, Bethesda, MD 20892 USA.
[Brambilla, Paolo] Univ Milano Bicocca, Dept Expt Med, Monza, Italy.
[Burnett, Mary S.; Epstein, Stephen E.] MedStar Hlth Res Inst, Hyattsville, MD USA.
[Cesana, Giancarlo] Univ Milano Bicocca, Res Ctr Publ Hlth, Monza, Italy.
[Dimitriou, Maria; Dedoussis, George] Harokopio Univ, Dept Dietet Nutr, Athens, Greece.
[Doering, Angela; Meisinger, Christa] Helmholtz Zentrum Munchen, Inst Epidemiol 1, Neuherberg, Germany.
[Doering, Angela] Helmholtz Zentrum Munchen, Inst Epidemiol 2, Neuherberg, Germany.
[Elliott, Paul; Jarvelin, Marjo-Riitta] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, MRC, Hlth Protect Agcy,Ctr Environm & Hlth, London, England.
[Eyjolfsson, Gudmundur Ingi] Lab Mjodd, Reykjavik, Iceland.
[Gigante, Bruna; de Faire, Ulf] Karolinska Inst, Inst Environm Med, Div Cardiovasc Epidemiol, S-10401 Stockholm, Sweden.
[Goodarzi, Mark O.; Jones, Michelle R.] Cedars Sinai Med Ctr, Dept Med, Div Endocrinol Diabet & Metab, Los Angeles, CA 90048 USA.
[Grallert, Harald; Illig, Thomas; Klopp, Norman] Helmholtz Zentrum Munchen, Res Unit Mol Epidemiol, Neuherberg, Germany.
[Groves, Christopher J.; McCarthy, Mark I.] Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford, England.
[Hallmans, Goran] Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden.
[Hartikainen, Anna-Liisa; Pouta, Anneli] Oulu Univ Hosp, Dept Clin Sci Obstet & Gynecol, Oulu, Finland.
[Hayward, Caroline] Western Gen Hosp, Inst Genet & Mol Med, MRC, Human Genet Unit, Edinburgh EH4 2XU, Midlothian, Scotland.
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[Hicks, Andrew A.; Pramstaller, Peter P.] European Acad Bozen Bolzano EURAC, Ctr Biomed, Bolzano, Italy.
[Hicks, Andrew A.; Pramstaller, Peter P.] Univ Lubeck, Affiliated Inst, Lubeck, Germany.
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[Illig, Thomas; Klopp, Norman] Hannover Med Sch, Hannover Unified Biobank, Hannover, Germany.
[Kastelein, John J. P.; Hovingh, G. Kees] Univ Amsterdam, Acad Med Ctr, Dept Vasc Med, NL-1105 AZ Amsterdam, Netherlands.
[Khaw, Kay-Tee] Univ Cambridge, Clin Gerontol Unit, Cambridge, England.
[Komulainen, Pirjo; Lakka, Timo A.; Rauramaa, Rainer] Kuopio Res Inst Exercise Med, Kuopio, Finland.
[Lin, Shih-Yi] Natl Yang Ming Univ, Sch Med, Taichung Vet Gen Hosp, Dept Internal Med,Div Endocrine & Metab, Taipei 112, Taiwan.
[Lindstrom, Jaana; Tuomilehto, Jaakko] Natl Inst Hlth & Welf, Diabet Prevent Unit, Helsinki, Finland.
[Loos, Ruth J. F.] Icahn Sch Med Mt Sinai, Genet Obes & Related Metab Traits Program, New York, NY USA.
[Loos, Ruth J. F.] Icahn Sch Med Mt Sinai, Charles Bronfman Inst Personalized Med, New York, NY USA.
[Loos, Ruth J. F.] Icahn Sch Med Mt Sinai, Mindich Child Hlth & Dev Inst, New York, NY USA.
[McArdle, Wendy L.] Univ Bristol, Sch Social & Community Med, Bristol, Avon, England.
[Mueller, Gabrielle] Univ Dresden, Med Fac Carl Gustav Carus, Inst Med Informat & Biometr, Dresden, Germany.
[Nagaraja, Ramaiah] NIA, Genet Lab, Baltimore, MD 21224 USA.
[Nieminen, Tuomo V. M.] Univ Tampere, Sch Med, Dept Clin Pharmacol, FIN-33101 Tampere, Finland.
[Nieminen, Tuomo V. M.] Paijat Hame Cent Hosp, Dept Internal Med, Lahti, Finland.
[Nieminen, Tuomo V. M.] Univ Helsinki, Cent Hosp, Div Cardiol, Helsinki, Finland.
[Olafsson, Isleifur] Landspitali Univ Hosp, Dept Clin Biochem, Reykjavik, Iceland.
[Palotie, Aarno] Univ Helsinki, Dept Med Genet, Haartman Inst, Helsinki, Finland.
[Palotie, Aarno] Univ Helsinki, Cent Hosp, Helsinki, Finland.
[Palotie, Aarno] Wellcome Trust Sanger Inst, Genet Epidemiol Grp, Cambridge, England.
[Papamarkou, Theodore] UCL, Dept Stat Sci, London, England.
[Pouta, Anneli; Jarvelin, Marjo-Riitta] Natl Inst Hlth & Welf, Oulu, Finland.
[Rader, Daniel J.; Reilly, Muredach P.] Univ Penn, Translat Res Ctr, Perelman Sch Med, Cardiovasc Inst, Philadelphia, PA 19104 USA.
[Rader, Daniel J.; Reilly, Muredach P.] Univ Penn, Translat Res Ctr, Perelman Sch Med, Div Translat Med & Human Genet, Philadelphia, PA 19104 USA.
[Rivadeneira, Fernando; Uitterlinden, Andre G.; Hofman, Albert] Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands.
[Rivadeneira, Fernando; Uitterlinden, Andre G.] Erasmus Univ, Med Ctr, Dept Internal Med, Rotterdam, Netherlands.
[Rivadeneira, Fernando; Uitterlinden, Andre G.; Hofman, Albert] Netherlands Consortium Hlth Aging, Netherlands Genom Initiat, Leiden, Netherlands.
[Ruokonen, Aimo] Univ Oulu, Dept Clin Sci Clin Chem, Oulu, Finland.
[Samani, Nilesh] Glenfield Gen Hosp, Natl Inst Hlth Res, Leicester Cardiovasc Biomed Res Unit, Leicester LE3 9QP, Leics, England.
[Samani, Nilesh] Univ Leicester, Glenfield Hosp, Dept Cardiovasc Sci, Leicester, Leics, England.
[Scharnagl, Hubert; Maerz, Winfried] Med Univ Graz, Clin Inst Med & Chem Lab Diagnost, Graz, Austria.
[Seeley, Janet] Univ E Anglia, Sch Int Dev, Norwich NR4 7TJ, Norfolk, England.
[Stancakova, Alena] Univ Eastern Finland, Dept Med, Kuopio, Finland.
[Stancakova, Alena] Kuopio Univ Hosp, SF-70210 Kuopio, Finland.
[Tiret, Laurence] Univ Paris 04, INSERM, UMRS 937, Paris, France.
[van Pelt, L. Joost] Univ Groningen, Univ Med Ctr Groningen, Dept Lab Med, Groningen, Netherlands.
[van Pelt, L. Joost; Wijmenga, Cisca; Wolffenbuttel, Bruce H. R.] Univ Groningen, Univ Med Ctr Groningen, Groningen, Netherlands.
[Wijmenga, Cisca] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, Groningen, Netherlands.
[Willemsen, Gonneke; Boomsma, Dorret I.] Vrije Univ Amsterdam, Dept Biol Psychol, Amsterdam, Netherlands.
[Wilsgaard, Tom; Njolstad, Inger] Univ Tromso, Fac Hlth Sci, Dept Community Med, Tromso, Norway.
[Adair, Linda S.] Univ N Carolina, Dept Nutr, Chapel Hill, NC USA.
[Arveiler, Dominique] Univ Strasbourg, Fac Med, Dept Epidemiol & Publ Hlth, Strasbourg, France.
[Assimes, Themistocles L.; Quertermous, Thomas] Stanford Univ, Sch Med, Dept Med, Stanford, CA 94305 USA.
[Bandinelli, Stefania] Azienda Sanit Firenze, Geriatr Unit, Florence, Italy.
[Bennett, Franklyn] Univ W Indies, Dept Pathol, Mona, Jamaica.
[Bochud, Murielle; Bovet, Pascal] Univ Lausanne Hosp, Inst Social & Prevent Med IUMSP, Lausanne, Switzerland.
[Boehm, Bernhard O.] Univ Ulm, Med Ctr, Dept Internal Med, Div Endocrinol & Diabet, D-89069 Ulm, Germany.
[Boehm, Bernhard O.] Nanyang Technol Univ, Lee Kong Chian Sch Med, Singapore 639798, Singapore.
[Bornstein, Stefan R.; Schwarz, Peter E. H.] Univ Dresden, Med Fac Carl Gustav Carus, Dept Med 3, Dresden, Germany.
[Bovet, Pascal] Minist Hlth, Victoria, Seychelles.
[Burnier, Michel] Univ Lausanne Hosp, Serv Nephrol, Lausanne, Switzerland.
[Chambers, John C.; Kooner, Jaspal S.] Imperial Coll Healthcare Natl Hlth Serv NHS Trust, London, England.
[Chen, Yii-Der Ida] Cedars Sinai Med Ctr, Dept Obstet & Gynecol, Div Reprod Endocrinol, Los Angeles, CA 90048 USA.
[Chen, Yii-Der Ida] Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA.
[Cooper, Richard S.; Tayo, Bamidele O.] Loyola Univ, Sch Med, Dept Prevent Med & Epidemiol, Maywood, IL 60153 USA.
[Feranil, Alan B.] Univ San Carlos, Off Populat Studies Fdn, Talamban, Cebu City, Philippines.
[Ferrieres, Jean] Toulouse Univ, Sch Med, Rangueil Hosp, Dept Cardiol, Toulouse, France.
[Freimer, Nelson B.] Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA USA.
[Groop, Leif C.] Lund Univ, Dept Clin Sci, Malmo, Sweden.
[Groop, Leif C.] Helsinki Univ Hosp, Dept Med, Helsinki, Finland.
[Gudnason, Vilmundur] Iceland Heart Assoc, Kopavogur, Iceland.
[Hamsten, Anders] Karolinska Univ Hosp, Dept Cardiol, Stockholm, Sweden.
[Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
[Hsiung, Chao Agnes] Natl Hlth Res Inst, Inst Populat Hlth Sci, Zhunan, Taiwan.
[Humphries, Steve E.] UCL, Inst Cardiovasc Sci, British Heart Fdn Labs, London, England.
[Hunt, Steven C.] Univ Utah, Sch Med, Salt Lake City, UT USA.
[Hveem, Kristian] Norwegian Univ Sci & Technol, Dept Publ Hlth & Gen Practice, Nord Trondelag Hlth Study HUNT Res Ctr, Levanger, Norway.
[Jarvelin, Marjo-Riitta] Oulu Univ Hosp, Unit Primary Care, Oulu, Finland.
[Jula, Antti] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Turku, Finland.
[Kahonen, Mika] Univ Tampere, Sch Med, Dept Clin Physiol, FIN-33101 Tampere, Finland.
[Kaprio, Jaakko] Natl Inst Hlth & Welf, Dept Mental Hlth & Subst Abuse Serv, Helsinki, Finland.
[Kesaniemi, Antero] Univ Oulu, Dept Med, Inst Clin Med, Oulu, Finland.
[Kesaniemi, Antero] Oulu Univ Hosp, Clin Res Ctr, Oulu, Finland.
[Kooner, Jaspal S.] Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, Natl Heart & Lung Inst, London, England.
[Krauss, Ronald M.] Childrens Hosp Oakland, Res Inst, Oakland, CA 94609 USA.
[Kuusisto, Johanna; Laakso, Markku] Univ Eastern Finland, Dept Med, Kuopio, Finland.
[Kuusisto, Johanna; Laakso, Markku] Kuopio Univ Hosp, SF-70210 Kuopio, Finland.
[Kyvik, Kirsten O.] Univ So Denmark, Inst Reg Hlth Serv Res, Odense, Denmark.
[Kyvik, Kirsten O.] Odense Univ Hosp, Odense Patient Data Explorat Network OPEN, DK-5000 Odense, Denmark.
[Lakka, Timo A.] Univ Eastern Finland, Inst Biomed Physiol, Kuopio, Finland.
[Lind, Lars; Siegbahn, Agneta; Wallentin, Lars] Uppsala Univ, Dept Med Sci, Uppsala, Sweden.
[Martin, Nicholas G.; Whitfield, John B.] Royal Brisbane Hosp, Queensland Inst Med Res, Brisbane, Qld 4029, Australia.
[Maerz, Winfried] Synlab Acad, Synlab Serv, Mannheim, Germany.
[McKenzie, Colin A.] Univ W Indies, Res Inst Trop Med, Trop Metab Res Unit, Mona, Jamaica.
[Meneton, Pierre] Ctr Rech Cordeliers, INSERM, U872, Paris, France.
[Moilanen, Leena] Kuopio Univ Hosp, Dept Med, SF-70210 Kuopio, Finland.
[Pramstaller, Peter P.] Gen Cent Hosp, Dept Neurol, Bolzano, Italy.
[Pramstaller, Peter P.] Med Univ Lubeck, Dept Neurol, D-23538 Lubeck, Germany.
[Psaty, Bruce M.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA.
[Psaty, Bruce M.] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Psaty, Bruce M.] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA.
[Psaty, Bruce M.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA USA.
[Rauramaa, Rainer] Kuopio Univ Hosp, Dept Clin Physiol & Nucl Med, SF-70210 Kuopio, Finland.
[Saleheen, Danish] Ctr Noncommunicable Dis, Karachi, Pakistan.
[Saleheen, Danish] Univ Penn, Dept Med, Philadelphia, PA 19104 USA.
[Salomaa, Veikko] Natl Inst Hlth & Welf, Unit Chron Dis Epidemiol & Prevent, Helsinki, Finland.
[Saramies, Jouko] South Karelia Cent Hosp, Lappeenranta, Finland.
[Schwarz, Peter E. H.] German Ctr Diabet Res DZD, Paul Langerhans Inst Dresden, Dresden, Germany.
[Sheu, Wayne H-H] Taichung Vet Gen Hosp, Dept Internal Med, Div Endocrine & Metab, Taichung, Taiwan.
[Shuldiner, Alan R.] Vet Adm Med Ctr, Geriatr Res & Educ Clin Ctr, Baltimore, MD 21218 USA.
[Stefansson, Kari; Thorsteinsdottir, Unnur] Univ Iceland, Fac Med, Reykjavik, Iceland.
[Strachan, David P.] Univ London, Div Populat Hlth Sci & Educ, London, England.
[Tremoli, Elena] Univ Milan, IRCCS, Monzino Cardiol Ctr, Dept Pharmacol Sci, Milan, Italy.
[Tuomilehto, Jaakko] Danube Univ Krems, Ctr Vasc Prevent, Krems, Austria.
[Tuomilehto, Jaakko] King Abdulaziz Univ, Fac Med, Jeddah 21413, Saudi Arabia.
[Tuomilehto, Jaakko] Hosp Univ La Paz, Grp RD06 0014 0015, Red Red Temat Invest Cooperat Enfermedades Cardio, Madrid, Spain.
[Uusitupa, Matti] Univ Eastern Finland, Inst Publ Hlth & Clin Nutr, Kuopio, Finland.
[Uusitupa, Matti] Kuopio Univ Hosp, Res Unit, SF-70210 Kuopio, Finland.
[Vollenweider, Peter] Univ Lausanne Hosp, Dept Med, Lausanne, Switzerland.
[Wolffenbuttel, Bruce H. R.] Univ Groningen, Univ Med Ctr Groningen, Dept Endocrinol, Groningen, Netherlands.
[Ordovas, Jose M.] Natl Ctr Cardiovasc Invest, Dept Cardiovasc Epidemiol & Populat Genet, Madrid, Spain.
[Ordovas, Jose M.] Madrid Inst Adv Studies Alimentac, Madrid, Spain.
[Ordovas, Jose M.] Tufts Univ, Human Nutr Res Ctr Aging, Jean Mayer USDA, Nutr & Genom Lab, Boston, MA 02111 USA.
[Franks, Paul W.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Cupples, L. Adrienne] Framingham Heart Dis Epidemiol Study, Framingham, MA USA.
[Rich, Stephen S.; Neale, Benjamin M.] Univ Virginia, Ctr Publ Hlth Genom, Charlottesville, VA USA.
[Daly, Mark J.] Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA.
RP Kathiresan, S (reprint author), Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA.
EM mjdaly@atgu.mgh.harvard.edu; bneale@broadinstitute.org;
skathiresan@partners.org
RI Hayward, Caroline/M-8818-2016; Schwarz, Peter/B-5127-2013; Wong,
Andrew/M-8899-2016; Magnusson, Patrik/C-4458-2017; Beckmann, Jacques S
/A-9772-2008; Feitosa, Mary/K-8044-2012; Hicks, Andrew/E-9518-2017;
Grallert, Harald/B-3424-2013; Gudnason, Vilmundur/K-6885-2015; Ripatti,
Samuli/H-9446-2014; Wilson, James F/A-5704-2009; Rivadeneira,
Fernando/O-5385-2015; Lyytikainen, Leo-Pekka/C-8544-2016; Bovet,
Pascal/F-4477-2011; Rudan, Igor/I-1467-2012; Papamarkou,
Theodore/A-2958-2012; Kyvik, Kirsten /K-5680-2016; Study,
GoDARTS/K-9448-2016; Bochud, Murielle/A-3981-2010; mangino,
massimo/F-5134-2011; Altshuler, David/A-4476-2009; Shah,
Sonia/N-7547-2013; Boehm, Bernhard/F-8750-2015; Colaus,
PsyColaus/K-6607-2013; Hypponen, Elina/B-2596-2014; Meisinger,
Christine/B-5358-2014; Hsiung, Chao Agnes/E-3994-2010; Wijmenga,
Cisca/D-2173-2009; Chang, Hsing-Yi /E-3973-2010; Palmer,
Colin/C-7053-2008; Pramstaller, Peter/C-2357-2008; Deloukas,
Panos/B-2922-2013; Strawbridge, Rona/H-5422-2012
OI Wolffenbuttel, Bruce H.R./0000-0001-9262-6921; Mitchell,
Braxton/0000-0003-4920-4744; Kaprio, Jaakko/0000-0002-3716-2455;
Johansson, Asa/0000-0002-2915-4498; Kleber, Marcus/0000-0003-0663-7275;
Martin, Nicholas/0000-0003-4069-8020; Ganna, Andrea/0000-0002-8147-240X;
Lakka, Timo/0000-0002-9199-2871; Franks, Paul/0000-0002-0520-7604;
Meisinger, Christa/0000-0002-9026-6544; Gigante,
Bruna/0000-0003-4508-7990; Humphries, Stephen E/0000-0002-8221-6547;
Gieger, Christian/0000-0001-6986-9554; Wijmenga,
Cisca/0000-0002-5635-1614; Kumari, Meena/0000-0001-9716-1035; Nieminen,
Tuomo/0000-0003-1755-1688; Jarvelin, Marjo-Riitta/0000-0002-2149-0630;
Shungin, Dmitry/0000-0001-7900-5856; Seeley, Janet/0000-0002-0583-5272;
Song, Ci/0000-0002-0947-9068; TREMOLI, ELENA/0000-0002-0929-6106; sanna,
serena/0000-0002-3768-1749; Kivimaki, Mika/0000-0002-4699-5627; Johnson,
Toby/0000-0002-5998-3270; Fraser, Ross/0000-0003-0488-2592; Esko,
Tonu/0000-0003-1982-6569; Hayward, Caroline/0000-0002-9405-9550;
Schwarz, Peter/0000-0001-6317-7880; Wong, Andrew/0000-0003-2079-4779;
Beckmann, Jacques S /0000-0002-9741-1900; Feitosa,
Mary/0000-0002-0933-2410; Hicks, Andrew/0000-0001-6320-0411; Willer,
Cristen/0000-0001-5645-4966; Kaakinen, Marika/0000-0002-9228-0462;
Sidore, Carlo/0000-0001-7504-7477; Gudnason,
Vilmundur/0000-0001-5696-0084; Ripatti, Samuli/0000-0002-0504-1202;
Wilson, James F/0000-0001-5751-9178; Rivadeneira,
Fernando/0000-0001-9435-9441; Lyytikainen,
Leo-Pekka/0000-0002-7200-5455; Bovet, Pascal/0000-0002-0242-4259; Rudan,
Igor/0000-0001-6993-6884; Papamarkou, Theodore/0000-0002-9689-543X;
Kyvik, Kirsten /0000-0003-2981-0245; Bochud,
Murielle/0000-0002-5727-0218; mangino, massimo/0000-0002-2167-7470;
Altshuler, David/0000-0002-7250-4107; Shah, Sonia/0000-0001-5860-4526;
Hypponen, Elina/0000-0003-3670-9399; Palmer, Colin/0000-0002-6415-6560;
Deloukas, Panos/0000-0001-9251-070X; Strawbridge,
Rona/0000-0001-8506-3585
FU Massachusetts General Hospital; Donovan Family Foundation; US National
Institutes of Health [R01HL107816]; Fondation Leducq; Canadian
Institutes of Health Research; National Heart, Lung, and Blood Institute
[T32HL007208]
FX We thank the Global Lipids Genetics Consortium for early access to the
association results of the Metabochip study. S. Kathiresan is supported
by a Research Scholar award from the Massachusetts General Hospital, the
Howard Goodman Fellowship from Massachusetts General Hospital, the
Donovan Family Foundation, R01HL107816 from the US National Institutes
of Health and a grant from Fondation Leducq. R.D. is supported by a
Banting Fellowship from the Canadian Institutes of Health Research. G.
P. is supported by award T32HL007208 from the National Heart, Lung, and
Blood Institute. The content is solely the responsibility of the authors
and does not necessarily represent the official views of the National
Heart, Lung, and Blood Institute or the US National Institutes of
Health.
NR 34
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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 2013
VL 45
IS 11
BP 1345
EP +
DI 10.1038/ng.2795
PG 9
WC Genetics & Heredity
SC Genetics & Heredity
GA 244JL
UT WOS:000326384100015
PM 24097064
ER
PT J
AU Zhan, XW
Larson, DE
Wang, CL
Koboldt, DC
Sergeev, YV
Fulton, RS
Fulton, LL
Fronick, CC
Branham, KE
Bragg-Gresham, J
Jun, G
Hu, YN
Kang, HM
Liu, DJ
Othman, M
Brooks, M
Ratnapriya, R
Boleda, A
Grassmann, F
von Strachwitz, C
Olson, LM
Buitendijk, GHS
Hofman, A
van Duijn, CM
Cipriani, V
Moore, AT
Shahid, H
Jiang, YD
Conley, YP
Morgan, DJ
Kim, IK
Johnson, MP
Cantsilieris, S
Richardson, AJ
Guymer, RH
Luo, HR
Ouyang, H
Licht, C
Pluthero, FG
Zhang, MM
Zhang, K
Baird, PN
Blangero, J
Klein, ML
Farrer, LA
DeAngelis, MM
Weeks, DE
Gorin, MB
Yates, JRW
Klaver, CCW
Pericak-Vance, MA
Haines, JL
Weber, BHF
Wilson, RK
Heckenlively, JR
Chew, EY
Stambolian, D
Mardis, ER
Swaroop, A
Abecasis, GR
AF Zhan, Xiaowei
Larson, David E.
Wang, Chaolong
Koboldt, Daniel C.
Sergeev, Yuri V.
Fulton, Robert S.
Fulton, Lucinda L.
Fronick, Catrina C.
Branham, Kari E.
Bragg-Gresham, Jennifer
Jun, Goo
Hu, Youna
Kang, Hyun Min
Liu, Dajiang
Othman, Mohammad
Brooks, Matthew
Ratnapriya, Rinki
Boleda, Alexis
Grassmann, Felix
von Strachwitz, Claudia
Olson, Lana M.
Buitendijk, Gabrielle H. S.
Hofman, Albert
van Duijn, Cornelia M.
Cipriani, Valentina
Moore, Anthony T.
Shahid, Humma
Jiang, Yingda
Conley, Yvette P.
Morgan, Denise J.
Kim, Ivana K.
Johnson, Matthew P.
Cantsilieris, Stuart
Richardson, Andrea J.
Guymer, Robyn H.
Luo, Hongrong
Ouyang, Hong
Licht, Christoph
Pluthero, Fred G.
Zhang, Mindy M.
Zhang, Kang
Baird, Paul N.
Blangero, John
Klein, Michael L.
Farrer, Lindsay A.
DeAngelis, Margaret M.
Weeks, Daniel E.
Gorin, Michael B.
Yates, John R. W.
Klaver, Caroline C. W.
Pericak-Vance, Margaret A.
Haines, Jonathan L.
Weber, Bernhard H. F.
Wilson, Richard K.
Heckenlively, John R.
Chew, Emily Y.
Stambolian, Dwight
Mardis, Elaine R.
Swaroop, Anand
Abecasis, Goncalo R.
TI Identification of a rare coding variant in complement 3 associated with
age-related macular degeneration
SO NATURE GENETICS
LA English
DT Article
ID HEMOLYTIC-UREMIC SYNDROME; GENOME-WIDE ASSOCIATION; FACTOR-H
POLYMORPHISM; COMMON DISEASES; SEQUENCING DATA; EYE DISEASE; FACTOR-B;
RISK; SUSCEPTIBILITY; MUTATIONS
AB Macular degeneration is a common cause of blindness in the elderly. To identify rare coding variants associated with a large increase in risk of age-related macular degeneration (AMD), we sequenced 2,335 cases and 789 controls in 10 candidate loci (57 genes). To increase power, we augmented our control set with ancestry-matched exome-sequenced controls. An analysis of coding variation in 2,268 AMD cases and 2,268 ancestry-matched controls identified 2 large-effect rare variants: previously described p. Arg1210Cys encoded in the CFH gene (case frequency (f(case)) = 0.51%; control frequency (f(control)) = 0.02%; odds ratio (OR) = 23.11) and newly identified p. Lys155Gln encoded in the C3 gene (f(case) = 1.06%; f(control) = 0.39%; OR = 2.68). The variants suggest decreased inhibition of C3 by complement factor H, resulting in increased activation of the alternative complement pathway, as a key component of disease biology.
C1 [Zhan, Xiaowei; Wang, Chaolong; Bragg-Gresham, Jennifer; Jun, Goo; Hu, Youna; Kang, Hyun Min; Liu, Dajiang; Abecasis, Goncalo R.] Univ Michigan, Sch Publ Hlth, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48109 USA.
[Larson, David E.; Koboldt, Daniel C.; Fulton, Robert S.; Fulton, Lucinda L.; Fronick, Catrina C.; Wilson, Richard K.; Mardis, Elaine R.] Washington Univ, Sch Med, Genome Inst, St Louis, MO USA.
[Wang, Chaolong] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Sergeev, Yuri V.] NEI, Ophthalm Genet & Visual Funct Branch, Bethesda, MD 20892 USA.
[Branham, Kari E.; Othman, Mohammad; Heckenlively, John R.] Univ Michigan, Kellogg Eye Ctr, Dept Ophthalmol & Visual Sci, Ann Arbor, MI 48109 USA.
[Brooks, Matthew; Ratnapriya, Rinki; Boleda, Alexis; Swaroop, Anand] NEI, US Natl Inst Hlth, Neurobiol Neurodegenerat & Repair Lab, Bethesda, MD 20892 USA.
[Grassmann, Felix; Weber, Bernhard H. F.] Univ Regensburg, Inst Human Genet, D-93053 Regensburg, Germany.
[von Strachwitz, Claudia] Southwest Eye Ctr, Stuttgart, Germany.
[Olson, Lana M.; Haines, Jonathan L.] Vanderbilt Univ, Sch Med, Ctr Human Genet Res, Nashville, TN 37212 USA.
[Olson, Lana M.; Haines, Jonathan L.] Vanderbilt Univ, Sch Med, Dept Mol Physiol & Biophys, Nashville, TN 37212 USA.
[Buitendijk, Gabrielle H. S.; Klaver, Caroline C. W.] Erasmus MC, Dept Ophthalmol, Rotterdam, Netherlands.
[Buitendijk, Gabrielle H. S.; Hofman, Albert; van Duijn, Cornelia M.; Klaver, Caroline C. W.] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.
[Hofman, Albert] Netherlands Genom Initiat, Netherlands Consortium Hlth Aging, The Hague, Netherlands.
[Cipriani, Valentina; Moore, Anthony T.; Yates, John R. W.] UCL, UCL Inst Ophthalmol, London, England.
[Cipriani, Valentina; Moore, Anthony T.; Yates, John R. W.] Moorfields Eye Hosp, London, England.
[Shahid, Humma; Yates, John R. W.] Univ Cambridge, Cambridge Inst Med Res, Dept Med Genet, Cambridge, England.
[Shahid, Humma] Cambridge Univ Hosp Natl Hlth Serv NHS Fdn Trust, Cambridge, England.
[Jiang, Yingda; Weeks, Daniel E.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15261 USA.
[Conley, Yvette P.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Hlth Promot & Dev, Pittsburgh, PA USA.
[Morgan, Denise J.; DeAngelis, Margaret M.] Univ Utah, John A Moran Eye Ctr, Dept Ophthalmol & Visual Sci, Salt Lake City, UT USA.
[Kim, Ivana K.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Retina Serv, Boston, MA USA.
[Kim, Ivana K.] Harvard Univ, Massachusetts Eye & Ear Infirm, Sch Med, Boston, MA USA.
[Johnson, Matthew P.; Blangero, John] Texas Biomed Res Inst, San Antonio, TX USA.
[Cantsilieris, Stuart; Richardson, Andrea J.; Guymer, Robyn H.; Baird, Paul N.] Univ Melbourne, Royal Victorian Eye & Ear Hosp, Ctr Eye Res Australia, East Melbourne, Vic, Australia.
[Luo, Hongrong; Ouyang, Hong; Zhang, Mindy M.; Zhang, Kang] Univ Calif San Diego, Dept Ophthalmol, Shiley Eye Ctr, La Jolla, CA 92093 USA.
[Luo, Hongrong; Ouyang, Hong; Zhang, Mindy M.; Zhang, Kang] Univ Calif San Diego, Inst Genom Med, La Jolla, CA 92093 USA.
[Licht, Christoph] Hosp Sick Children, Dept Pediat, Toronto, ON M5G 1X8, Canada.
[Pluthero, Fred G.] Hosp Sick Children, Cell Biol Program, Toronto, ON M5G 1X8, Canada.
[Klein, Michael L.] Oregon Hlth & Sci Univ, Casey Eye Inst, Macular Degenerat Ctr, Portland, OR 97201 USA.
[Farrer, Lindsay A.] Boston Univ, Sch Med, Dept Med, Sect Biomed Genet, Boston, MA 02118 USA.
[Farrer, Lindsay A.] Boston Univ, Sch Publ Hlth, Boston, MA 02118 USA.
[Farrer, Lindsay A.] Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02118 USA.
[Farrer, Lindsay A.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Farrer, Lindsay A.] Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA.
[Farrer, Lindsay A.] Boston Univ, Sch Med, Dept Ophthalmol, Boston, MA 02118 USA.
[Weeks, Daniel E.] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Human Genet, Pittsburgh, PA 15261 USA.
[Gorin, Michael B.] Univ Calif Los Angeles, David Geffen Sch Med, Jules Stein Eye Inst, Dept Ophthalmol, Los Angeles, CA 90095 USA.
[Pericak-Vance, Margaret A.] Univ Miami, Miller Sch Med, John P Hussman Inst Human Genom, Miami, FL 33136 USA.
[Chew, Emily Y.] NEI, US Natl Inst Hlth, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA.
[Stambolian, Dwight] Univ Penn, Sch Med, Dept Ophthalmol & Human Genet, Philadelphia, PA 19104 USA.
RP Abecasis, GR (reprint author), Univ Michigan, Sch Publ Hlth, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48109 USA.
EM goncalo@umich.edu
RI Cipriani, Valentina/A-8549-2012; luo, hongrong/B-2714-2015; DeAngelis,
e/J-7863-2015; Klaver, Caroline/A-2013-2016; Jun, Goo/M-5235-2016; Jun,
Goo/F-1941-2017;
OI Weeks, Daniel/0000-0001-9410-7228; Pluthero, Fred/0000-0002-0451-5840;
Baird, Paul/0000-0002-1305-3502; Swaroop, Anand/0000-0002-1975-1141;
Cipriani, Valentina/0000-0002-0839-9955; luo,
hongrong/0000-0001-7994-1193; Jun, Goo/0000-0003-0891-0204; Jun,
Goo/0000-0003-0891-0204; Farrer, Lindsay/0000-0001-5533-4225
FU US National Institutes of Health (National Eye Institute, National Human
Genome Research Institute) [EY022005, HG007022, HG005552, EY016862,
U54HG003079, EY09859]; Medical Research Council, UK [G0000067]; Deutsche
Forschungsgemeinschaft [WE1259/19-2]; Thome Memorial Foundation; Harold
and Pauline Price Foundation
FX We thank all study participants for their generous volunteering. We
thank B. Li, W. Chen, C. Sidore, T. Teslovich, L. Fritsche and M.
Boehnke for useful discussion and suggestions. This project was
supported by grants from the US National Institutes of Health (National
Eye Institute, National Human Genome Research Institute; grants
EY022005, HG007022, HG005552, EY016862, U54HG003079 and EY09859); the
Medical Research Council, UK (grant G0000067); the Deutsche
Forschungsgemeinschaft (grant WE1259/19-2); the Alcon Research
Institute; The UK Department of Health's National Institute for Health
Research (NIHR) Biomedical Research Centre for Ophthalmology at
Moorfields Eye Hospital and the UCL Institute of Ophthalmology; Research
to Prevent Blindness (New York); the Thome Memorial Foundation; the
Harold and Pauline Price Foundation; and the National Health and Medical
Research Council of Australia (NHMRC) Clinical Research Excellence
(grant 529923, NHMRC practitioner fellowship 529905 and NHMRC Senior
Research Fellowship 1028444). The study was also supported by the
Intramural Research Program (Computational Medicine Initiative) of the
National Eye Institute. The Centre for Eye Research Australia (CERA)
receives operational infrastructure support from the Victorian
Government. The views expressed in the publication are those of the
authors and not necessarily those of their employers or the funders.
NR 43
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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 2013
VL 45
IS 11
BP 1375
EP +
DI 10.1038/ng.2758
PG 7
WC Genetics & Heredity
SC Genetics & Heredity
GA 244JL
UT WOS:000326384100020
PM 24036949
ER
PT J
AU Flannick, J
Beer, NL
Bick, AG
Agarwala, V
Molnes, J
Gupta, N
Burtt, NP
Florez, JC
Meigs, JB
Taylor, H
Lyssenko, V
Irgens, H
Fox, E
Burslem, F
Johansson, S
Brosnan, MJ
Trimmer, JK
Newton-Cheh, C
Tuomi, T
Molven, A
Wilson, JG
O'Donnell, CJ
Kathiresan, S
Hirschhorn, JN
Njolstad, PR
Rolph, T
Seidman, JG
Gabriel, S
Cox, DR
Seidman, CE
Groop, L
Altshuler, D
AF Flannick, Jason
Beer, Nicola L.
Bick, Alexander G.
Agarwala, Vineeta
Molnes, Janne
Gupta, Namrata
Burtt, Noel P.
Florez, Jose C.
Meigs, James B.
Taylor, Herman
Lyssenko, Valeriya
Irgens, Henrik
Fox, Ervin
Burslem, Frank
Johansson, Stefan
Brosnan, M. Julia
Trimmer, Jeff K.
Newton-Cheh, Christopher
Tuomi, Tiinamaija
Molven, Anders
Wilson, James G.
O'Donnell, Christopher J.
Kathiresan, Sekar
Hirschhorn, Joel N.
Njolstad, Pal R.
Rolph, Tim
Seidman, J. G.
Gabriel, Stacey
Cox, David R.
Seidman, Christine E.
Groop, Leif
Altshuler, David
TI Assessing the phenotypic effects in the general population of rare
variants in genes for a dominant Mendelian form of diabetes
SO NATURE GENETICS
LA English
DT Article
ID BURROWS-WHEELER TRANSFORM; NORWEGIAN MODY REGISTRY; BETA-CELL FUNCTION;
FACTOR-I; NUCLEAR FACTOR-1-ALPHA; READ ALIGNMENT; ALPHA-GENE; YOUNG
MODY; ONSET; MUTATIONS
AB Genome sequencing can identify individuals in the general population who harbor rare coding variants in genes for Mendelian disorders1-7 and who may consequently have increased disease risk. Previous studies of rare variants in phenotypically extreme individuals display ascertainment bias and may demonstrate inflated effect-size estimates8-12. We sequenced seven genes for maturity-onset diabetes of the young (MODY) 13 in well-phenotyped population samples14,15 (n = 4,003). We filtered rare variants according to two prediction criteria for disease-causing mutations: reported previously in MODY or satisfying stringent de novo thresholds (rare, conserved and protein damaging). Approximately 1.5% and 0.5% of randomly selected individuals from the Framingham and Jackson Heart Studies, respectively, carry variants from these two classes. However, the vast majority of carriers remain euglycemic through middle age. Accurate estimates of variant effect sizes from population-based sequencing are needed to avoid falsely predicting a substantial fraction of individuals as being at risk for MODY or other Mendelian diseases.
C1 [Flannick, Jason; Beer, Nicola L.; Bick, Alexander G.; Agarwala, Vineeta; Gupta, Namrata; Burtt, Noel P.; Florez, Jose C.; Newton-Cheh, Christopher; Kathiresan, Sekar; Hirschhorn, Joel N.; Njolstad, Pal R.; Gabriel, Stacey; Altshuler, David] Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA.
[Flannick, Jason; Altshuler, David] Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA.
[Flannick, Jason] Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA.
[Bick, Alexander G.; Hirschhorn, Joel N.; Seidman, J. G.; Seidman, Christine E.; Altshuler, David] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA.
[Agarwala, Vineeta] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA.
[Agarwala, Vineeta] Harvard Univ, Grad Sch Arts & Sci, Program Biophys, Cambridge, MA 02138 USA.
[Molnes, Janne; Irgens, Henrik; Johansson, Stefan; Molven, Anders; Njolstad, Pal R.] Univ Bergen, KG Jebsen Ctr Diabet Res, Dept Clin Sci, Bergen, Norway.
[Florez, Jose C.; Newton-Cheh, Christopher; Kathiresan, Sekar] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA.
[Florez, Jose C.; Meigs, James B.; Altshuler, David] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Meigs, James B.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA.
[Taylor, Herman; Fox, Ervin] Univ Mississippi, Med Ctr, Dept Med, Jackson, MS 39216 USA.
[Taylor, Herman] Jackson State Univ, Jackson, MS USA.
[Taylor, Herman] Tougaloo Coll, Div Nat Sci, Tougaloo, MS USA.
[Lyssenko, Valeriya; Groop, Leif] Lund Univ, Clin Res Ctr, Dept Clin Sci Diabet & Endocrinol, Malmo, Sweden.
[Irgens, Henrik; Njolstad, Pal R.] Haukeland Hosp, Dept Pediat, N-5021 Bergen, Norway.
[Burslem, Frank] Prescient Life Sci, Cardiovasc & Metab Dis Practice, London, England.
[Johansson, Stefan] Haukeland Hosp, Ctr Med Genet & Mol Med, N-5021 Bergen, Norway.
[Brosnan, M. Julia; Trimmer, Jeff K.; Rolph, Tim] Pfizer Inc, Cardiovasc & Metab Dis Res Unit, Cambridge, MA USA.
[Newton-Cheh, Christopher; O'Donnell, Christopher J.] Natl Heart Lung & Blood Inst Framingham Heart Stu, Framingham, MA USA.
[Newton-Cheh, Christopher; O'Donnell, Christopher J.; Kathiresan, Sekar] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA.
[Tuomi, Tiinamaija] Univ Helsinki, Dept Gen Practice & Primary Hlth Care, Helsinki, Finland.
[Tuomi, Tiinamaija] Univ Helsinki, Cent Hosp, Dept Med, Helsinki, Finland.
[Tuomi, Tiinamaija] Univ Helsinki, Cent Hosp, Res Program Mol Med, Helsinki, Finland.
[Molven, Anders] Univ Bergen, Dept Clin Med, Gade Lab Pathol, Bergen, Norway.
[Molven, Anders] Haukeland Hosp, Dept Pathol, N-5021 Bergen, Norway.
[Wilson, James G.] Univ Mississippi, Med Ctr, Dept Physiol & Biophys, Jackson, MS 39216 USA.
[O'Donnell, Christopher J.] NHLBI, Div Intramural Res, Bethesda, MD 20892 USA.
[Hirschhorn, Joel N.] Childrens Hosp, Div Genet, Boston, MA 02115 USA.
[Hirschhorn, Joel N.] Childrens Hosp, Div Endocrinol, Boston, MA 02115 USA.
[Hirschhorn, Joel N.] Childrens Hosp, Program Genom, Boston, MA 02115 USA.
[Cox, David R.] Pfizer Inc, Appl Quantitat Genotherapeut, San Francisco, CA USA.
[Seidman, Christine E.] Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02115 USA.
[Seidman, Christine E.] Howard Hughes Med Inst, Chevy Chase, MD USA.
[Groop, Leif] Univ Helsinki, Finnish Inst Mol Med, Helsinki, Finland.
RP Altshuler, D (reprint author), Broad Inst Harvard & MIT, Program Med & Populat Genet, Cambridge, MA USA.
EM altshuler@molbio.mgh.harvard.edu
RI Altshuler, David/A-4476-2009; Johansson, Stefan/C-4394-2011;
OI Altshuler, David/0000-0002-7250-4107; Johansson,
Stefan/0000-0002-2298-7008; Tuomi, Tiinamaija/0000-0002-8306-6202
FU National Human Genome Research Institute of the US National Institutes
of Health (NIH) [U54 HG003067]; Howard Hughes Medical Institute; Pfizer
Inc.; NIH [5-T32-GM007748-33]; Fulbright Diabetes UK Fellowship [BDA
11/0004348]; Doris Duke Charitable Foundation [2006087]; National
Institute of Diabetes and Digestive and Kidney Diseases grant [K24
DK080140]; NHLBI [N01-HC-95170, N01-HC95171, N01-HC-95172]; National
Institute for Minority Health and Health Disparities; Norwegian Research
Council; European Research Council
FX We acknowledge the contribution of the participants of the Framingham
and Jackson Heart Study, as well as the participants from the Malm
Preventive Project, the Scania Diabetes Registry and the Botnia Study.
This work was supported by grants from the National Human Genome
Research Institute of the US National Institutes of Health (NIH)
(Medical Sequencing Program grant U54 HG003067 to the Broad Institute
principal investigator, E. Lander) and the Howard Hughes Medical
Institute, as well as funding from Pfizer Inc. J. F. was supported in
part by NIH training grant 5-T32-GM007748-33. N. L. B. was supported by
a Fulbright Diabetes UK Fellowship (BDA 11/0004348). D. A. was supported
by funding from the Doris Duke Charitable Foundation (2006087). J. M.
acknowledges support from National Institute of Diabetes and Digestive
and Kidney Diseases grant K24 DK080140. J. B. M. and J. C. F.
acknowledge support from NIH grant R01 DK078616. A. G. B. and V. A. were
supported by NIH Medical Scientist Training Program fellowship
T32GM007753. J. G. S. and C. E. S. were supported by NIH RO1
2R01HL080494, the National Heart, Lung, and Blood Institute (NHLBI) and
the LeDucq Foundation. The Jackson Heart Study is supported by contracts
N01-HC-95170, N01-HC95171 and N01-HC-95172 from the NHLBI, the National
Institute for Minority Health and Health Disparities and additional
support from the National Institute of Biomedical Imaging and
Bioengineering. The Framingham Heart Study was supported by contracts
N01-HC-25195 and 6R01-NS 17950 from the NHLBI and genotyping services
from Affymetrix, Inc. (contract N02-HL-6-4278 for the SNP Health
Association Resource, SHARe, project). The Malm Preventive Project and
the Scania Diabetes Registry were supported by a Swedish Research
Council grant (Linne) to the Lund University Diabetes Centre. The Botnia
study was supported by funding from the Sigrid Juselius Foundation and
the Folkh lsan Research Foundation, as well as a European Research
Council advanced research grant to L. G. (GA 269045). The MODY study was
supported by grants from the KG Jebsen Foundation, the Norwegian
Research Council, the University of Bergen, Helse Vest, Innovest and the
European Research Council (AdG).
NR 92
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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 2013
VL 45
IS 11
BP 1380
EP +
DI 10.1038/ng.2794
PG 8
WC Genetics & Heredity
SC Genetics & Heredity
GA 244JL
UT WOS:000326384100021
PM 24097065
ER
PT J
AU Fauci, AS
Folkers, GK
Dieffenbach, CW
AF Fauci, Anthony S.
Folkers, Gregory K.
Dieffenbach, Carl W.
TI HIV-AIDS: much accomplished, much to do
SO NATURE IMMUNOLOGY
LA English
DT Article
ID ANTIRETROVIRAL THERAPY; RISK BEHAVIORS; INFECTION; PREVENTION
AB As a result of decades of research-driven breakthroughs in basic and clinical science and recent advances in the broad-scale implementation of interventions for the prevention and treatment of infection with HIV, a turning point has been reached in the global HIV-AIDS pandemic. To end the pandemic and achieve the goal of an AIDS-free generation, researchers and clinicians must follow the dual pathway of optimizing the implementation of existing prevention and treatment interventions and discovering with basic and clinical research new and effective tools in both of these arenas.
C1 [Fauci, Anthony S.; Folkers, Gregory K.; Dieffenbach, Carl W.] NIAID, NIH, Bethesda, MD 20892 USA.
RP Fauci, AS (reprint author), NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM afauci@niaid.nih.gov
NR 25
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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 2013
VL 14
IS 11
BP 1104
EP 1107
PG 4
WC Immunology
SC Immunology
GA 239KV
UT WOS:000326023400003
PM 24145780
ER
PT J
AU Lee, YJ
Holzapfel, KL
Zhu, JF
Jameson, SC
Hogquist, KA
AF Lee, You Jeong
Holzapfel, Keli L.
Zhu, Jinfang
Jameson, Stephen C.
Hogquist, Kristin A.
TI Steady-state production of IL-4 modulates immunity in mouse strains and
is determined by lineage diversity of iNKT cells
SO NATURE IMMUNOLOGY
LA English
DT Article
ID CD8(+) T-CELLS; CD1D-RESTRICTED NKT CELLS; AIRWAY HYPERREACTIVITY;
CYTOKINE PRODUCTION; ZINC-FINGER; INNATE; RESPONSES; MICE; BET; ASTHMA
AB Invariant natural killer T cells (iNKT cells) can produce copious amounts of interleukin 4 (IL-4) early during infection. However, indirect evidence suggests they may produce this immunomodulatory cytokine in the steady state. Through intracellular staining for transcription factors, we have defined three subsets of iNKT cells (NKT1, NKT2 and NKT17) that produced distinct cytokines; these represented diverse lineages and not developmental stages, as previously thought. These subsets exhibited substantial interstrain variation in numbers. In several mouse strains, including BALB/c, NKT2 cells were abundant and were stimulated by self ligands to produce IL-4. In those strains, steady-state IL-4 conditioned CD8(+) T cells to become 'memory-like', increased serum concentrations of immunoglobulin E (IgE) and caused dendritic cells to produce chemokines. Thus, iNKT cell-derived IL-4 altered immunological properties under normal steady-state conditions.
C1 [Lee, You Jeong; Holzapfel, Keli L.; Jameson, Stephen C.; Hogquist, Kristin A.] Univ Minnesota, Dept Lab Med & Pathol, Dept Lab Med, Minneapolis, MN 55455 USA.
[Zhu, Jinfang] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA.
RP Hogquist, KA (reprint author), Univ Minnesota, Dept Lab Med & Pathol, Dept Lab Med, Minneapolis, MN 55455 USA.
EM hogqu001@umn.edu
RI Jameson, Stephen/D-9892-2013; Zhu, Jinfang/B-7574-2012;
OI Hogquist, Kristin/0000-0001-9963-5687
FU US National Institute of Health, Division of Intramural Research,
National Institute of Allergy and Infectious Diseases [R37-AI39560,
RO1-AI075168, T32 HD060536]; US National Cancer Research Institute
FX We thank J. Ding and S. Perry for technical support; M. Mohrs (Trudeau
Institute) for KN2 mice on the B6 and BALB/c background; D. B.
Sant'Angelo (Rutgers University) for Alexa Fluor 488-conjugated antibody
to PLZF; M. Mohrs and M. Kronenberg for discussions; and S. Hamilton for
critical review of the manuscript. Supported by the US National
Institutes of Health (R37-AI39560 to K. A. H.; RO1-AI075168 to S. C. J.;
T32 HD060536 to K. L. H.; and the Division of Intramural Research,
National Institute of Allergy and Infectious Diseases, for J.Z.) and the
Cancer Research Institute (Y.J.L.).
NR 46
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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 2013
VL 14
IS 11
BP 1146
EP U126
DI 10.1038/ni.2731
PG 10
WC Immunology
SC Immunology
GA 239KV
UT WOS:000326023400011
PM 24097110
ER
PT J
AU Hu, GQ
Tang, QS
Sharma, S
Yu, F
Escobar, TM
Muljo, SA
Zhu, JF
Zhao, KJ
AF Hu, Gangqing
Tang, Qingsong
Sharma, Suveena
Yu, Fang
Escobar, Thelma M.
Muljo, Stefan A.
Zhu, Jinfang
Zhao, Keji
TI Expression and regulation of intergenic long noncoding RNAs during T
cell development and differentiation
SO NATURE IMMUNOLOGY
LA English
DT Article
ID GENOME-WIDE IDENTIFICATION; TRANSCRIPTION FACTOR; GENE-EXPRESSION;
INTEGRATIVE ANNOTATION; CUTTING EDGE; STEM-CELLS; REVEALS; SEQ;
POPULATIONS; INTERFERON
AB Although intergenic long noncoding RNAs (lincRNAs) have been linked to gene regulation in various tissues, little is known about lincRNA transcriptomes in the T cell lineages. Here we identified 1,524 lincRNA clusters in 42 T cell samples, from early T cell progenitors to terminally differentiated helper T cell subsets. Our analysis revealed highly dynamic and cell-specific expression patterns for lincRNAs during T cell differentiation. These lincRNAs were located in genomic regions enriched for genes that encode proteins with immunoregulatory functions. Many were bound and regulated by the key transcription factors T-bet, GATA-3, STAT4 and STAT6. We found that the lincRNA LincR-Ccr2-5'AS, together with GATA-3, was an essential component of a regulatory circuit in gene expression specific to the T(H)2 subset of helper T cells and was important for the migration of T(H)2 cells.
C1 [Hu, Gangqing; Tang, Qingsong; Zhao, Keji] NHLBI, Syst Biol Ctr, NIH, Bethesda, MD 20892 USA.
[Sharma, Suveena; Yu, Fang; Escobar, Thelma M.; Muljo, Stefan A.; Zhu, Jinfang] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA.
RP Zhu, JF (reprint author), NIAID, Immunol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM jfzhu@niaid.nih.gov; zhaok@nhlbi.nih.gov
RI HU, GANGQING/K-5849-2012; Muljo, Stefan/F-5671-2015; Zhu,
Jinfang/B-7574-2012
OI Muljo, Stefan/0000-0003-1013-446X;
FU Division of Intramural Research of the NHLBI and NIAID (US National
Institutes of Health)
FX We thank the DNA Sequencing Core facility of the National Heart, Lung
and Blood Institute (NHLBI) for sequencing the ChIP-Seq and RNA-Seq
libraries; J. Edwards for most cell-sorting experiments; the flow
cytometry core of NHLBI for some cell-sorting experiments and analysis;
H. Cao for comments on the knockdown of lincRNA by shRNA; D. Northrup
for critical reading and editing of the manuscript; H. Zhang for sharing
experience with chemokines and chemokine receptors; P. Burr for RNA-Seq;
and X. Zheng for sharing code for binomial tests. This study used the
Biowulf Linux cluster of the US National Institutes of Health. Supported
by the Division of Intramural Research of the NHLBI and NIAID (US
National Institutes of Health).
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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 2013
VL 14
IS 11
BP 1190
EP U118
DI 10.1038/ni.2712
PG 11
WC Immunology
SC Immunology
GA 239KV
UT WOS:000326023400016
PM 24056746
ER
PT J
AU Regard, JB
Malhotra, D
Gvozdenovic-Jeremic, J
Josey, M
Chen, M
Weinstein, LS
Lu, JM
Shore, EM
Kaplan, FS
Yang, YZ
AF Regard, Jean B.
Malhotra, Deepti
Gvozdenovic-Jeremic, Jelena
Josey, Michelle
Chen, Min
Weinstein, Lee S.
Lu, Jianming
Shore, Eileen M.
Kaplan, Frederick S.
Yang, Yingzi
TI Activation of Hedgehog signaling by loss of GNAS causes heterotopic
ossification
SO NATURE MEDICINE
LA English
DT Article
ID PROTEIN-KINASE-A; SUPPRESSES OSTEOGENIC DIFFERENTIATION; MESENCHYMAL
STEM-CELLS; STIMULATORY G-PROTEIN; BONE-FORMATION; OSTEOBLAST
DIFFERENTIATION; IN-VIVO; CHONDROCYTE PROLIFERATION; PROMOTES
PROLIFERATION; SKELETAL DEVELOPMENT
AB Heterotopic ossification, the pathologic formation of extraskeletal bone, occurs as a common complication of trauma or in genetic disorders and can be disabling and lethal. However, the underlying molecular mechanisms are largely unknown. Here we demonstrate that G alpha(s) restricts bone formation to the skeleton by inhibiting Hedgehog signaling in mesenchymal progenitor cells. In progressive osseous heteroplasia, a human disease caused by null mutations in GNAS, which encodes G alpha(s), Hedgehog signaling is upregulated in ectopic osteoblasts and progenitor cells. In animal models, we show that genetically-mediated ectopic Hedgehog signaling is sufficient to induce heterotopic ossification, whereas inhibition of this signaling pathway by genetic or pharmacological means strongly reduces the severity of this condition. As our previous work has shown that GNAS gain-of-function mutations upregulate WNT-beta-catenin signaling in osteoblast progenitor cells, resulting in their defective differentiation and fibrous dysplasia, we identify G alpha(s) as a key regulator of proper osteoblast differentiation through its maintenance of a balance between the Wnt-beta-catenin and Hedgehog pathways. Also, given the results here of the pharmacological studies in our mouse model, we propose that Hedgehog inhibitors currently used in the clinic for other conditions, such as cancer, may possibly be repurposed for treating heterotopic ossification and other diseases caused by GNAS inactivation.
C1 [Regard, Jean B.; Malhotra, Deepti; Gvozdenovic-Jeremic, Jelena; Josey, Michelle; Yang, Yingzi] NHGRI, NIH, Bethesda, MD 20892 USA.
[Chen, Min; Weinstein, Lee S.] NIDDK, NIH, Bethesda, MD 20892 USA.
[Lu, Jianming] Codex BioSolut, Gaithersburg, MD USA.
[Shore, Eileen M.; Kaplan, Frederick S.] Univ Penn, Perelman Sch Med, Dept Orthopaed Surg, Philadelphia, PA 19104 USA.
[Shore, Eileen M.] Univ Penn, Dept Genet, Perelman Sch Med, Philadelphia, PA 19104 USA.
[Kaplan, Frederick S.] Univ Penn, Dept Med, Perelman Sch Med, Philadelphia, PA 19104 USA.
RP Yang, YZ (reprint author), NHGRI, NIH, Bethesda, MD 20892 USA.
EM jean.regard@novartis.com; yingzi@mail.nih.gov
FU intramural research program of NHGRI at the US National Institutes of
Health (NIH); intramural research program of NIDDK at the US National
Institutes of Health (NIH); Progressive Osseous Heteroplasia
Association; University of Pennsylvania Center for Research in FOP and
Related Disorders; Penn Center for Musculoskeletal Disorders (NIH NIAMS)
[P30-AR050950]; Isaac and Rose Nassau Professorship of Orthopaedic
Molecular Medicine; NIH NIAMS [R01-AR046831, R01-AR41916]
FX We thank the entire Yang lab for stimulating discussions. We thank J.
Fekecs and P. Andre for helping with the data illustration. The work in
the Yang and Weinstein labs was supported by the intramural research
programs of NHGRI and NIDDK at the US National Institutes of Health
(NIH), respectively. We thank R. Caron for his work on the POH lesion
histological analyses. The rabbit anti-Gli3 antibody was provided by S.
Mackem (NIH NCI), and the dnPKA adenovirus was a gift from C.-M. Fan
(Carnegie Institution for Science). The work in the Kaplan and Shore lab
was supported by the Progressive Osseous Heteroplasia Association, the
University of Pennsylvania Center for Research in FOP and Related
Disorders, the Penn Center for Musculoskeletal Disorders (NIH NIAMS
P30-AR050950), the Isaac and Rose Nassau Professorship of Orthopaedic
Molecular Medicine and NIH NIAMS (R01-AR046831 and R01-AR41916).
NR 73
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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 2013
VL 19
IS 11
BP 1505
EP +
DI 10.1038/nm.3314
PG 10
WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research &
Experimental
SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental
Medicine
GA 251IF
UT WOS:000326920300028
PM 24076664
ER
PT J
AU Simmons, WK
Rapuano, KM
Kallman, SJ
Ingeholm, JE
Miller, B
Gotts, SJ
Avery, JA
Hall, KD
Martin, A
AF Simmons, W. Kyle
Rapuano, Kristina M.
Kallman, Seth J.
Ingeholm, John E.
Miller, Bernard
Gotts, Stephen J.
Avery, Jason A.
Hall, Kevin D.
Martin, Alex
TI Category-specific integration of homeostatic signals in caudal but not
rostral human insula
SO NATURE NEUROSCIENCE
LA English
DT Article
ID HUMAN AWARENESS; ACTIVATION; FEELINGS; NUCLEUS; FOODS; TASTE; BODY
AB Prevailing theories hold that the insula is functionally organized along its caudal-to-rostral axis, with posterior regions coding lower-level sensory information and anterior regions coding higher-level stimulus significance relative to the body's homeostatic needs. Contrary to predictions of this model, the response of the taste-sensitive region of the caudal, but not rostral, insula to food images was directly related to the body's homeostatic state as indexed by levels of peripheral glucose.
C1 [Simmons, W. Kyle; Avery, Jason A.] Laureate Inst Brain Res, Tulsa, OK USA.
[Simmons, W. Kyle] Univ Tulsa, Fac Community Med, Tulsa, OK 74104 USA.
[Simmons, W. Kyle; Rapuano, Kristina M.; Kallman, Seth J.; Ingeholm, John E.; Gotts, Stephen J.; Martin, Alex] NIHM, Lab Brain & Cognit, NIH, Bethesda, MD USA.
[Miller, Bernard; Hall, Kevin D.] NIDDK, Lab Biol Modeling, NIH, Bethesda, MD 20892 USA.
[Avery, Jason A.] Univ Tulsa, Dept Biol Sci, Tulsa, OK 74104 USA.
RP Simmons, WK (reprint author), Laureate Inst Brain Res, Tulsa, OK USA.
EM wksimmons@laureateinstitute.org
RI Simmons, William/K-8925-2015
OI Simmons, William/0000-0002-0399-9003
FU NIMH [K01MH096175-01]; NIDDK; Oklahoma Center for the Advancement of
Science and Technology [OCAST HR10-141]; NARSAD; Oklahoma Tobacco
Research Center; William K. Warren Foundation
FX We would like to thank K. Burrows for help with data management and
analysis of the high-sweetness and low-sweetness food pictures. This
research supported by the Intramural Research Programs of the NIMH and
the NIDDK, as well as by NIMH grant K01MH096175-01 to W.K.S., a grant
from the Oklahoma Center for the Advancement of Science and Technology
(OCAST HR10-141) to W.K.S., a NARSAD Young Investigator Award to W.K.S.,
a grant to W.K.S. from the Oklahoma Tobacco Research Center, and The
William K. Warren Foundation. The study was conducted under NIH Clinical
Study Protocol 09-DK-0081 (ClinicalTrials.gov ID NCT00846040).
NR 16
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U1 0
U2 4
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 2013
VL 16
IS 11
BP 1551
EP 1552
DI 10.1038/nn.3535
PG 2
WC Neurosciences
SC Neurosciences & Neurology
GA 241YX
UT WOS:000326205700011
PM 24077565
ER
PT J
AU Chittajallu, R
Craig, MT
McFarland, A
Yuan, XQ
Geffen, S
Tricoire, L
Erkkila, B
Barron, SC
Lopez, CM
Liang, BJ
Jeffries, BW
Pelkey, KA
McBain, CJ
AF Chittajallu, Ramesh
Craig, Michael T.
McFarland, Ashley
Yuan, Xiaoqing
Geffen, Scott
Tricoire, Ludovic
Erkkila, Brian
Barron, Sean C.
Lopez, Carla M.
Liang, Barry J.
Jeffries, Brian W.
Pelkey, Kenneth A.
McBain, Chris J.
TI Dual origins of functionally distinct O-LM interneurons revealed by
differential 5-HT3AR expression
SO NATURE NEUROSCIENCE
LA English
DT Article
ID OSCILLATIONS IN-VITRO; STRATUM-ORIENS INTERNEURONS; CORTICAL
INTERNEURONS; GABAERGIC INTERNEURONS; NETWORK OSCILLATIONS; RAT
HIPPOCAMPUS; PERISOMATIC INHIBITION; RECEPTOR ACTIVATION; TRANSGENIC
MICE; BASKET CELLS
AB Forebrain circuits rely upon a relatively small but remarkably diverse population of GABAergic interneurons to bind and entrain large principal cell assemblies for network synchronization and rhythmogenesis. Despite the high degree of heterogeneity across cortical interneurons, members of a given subtype typically exhibit homogeneous developmental origins, neuromodulatory response profiles, morphological characteristics, neurochemical signatures and electrical features. Here we report a surprising divergence among hippocampal oriens-lacunosum moleculare (O-LM) projecting interneurons that have hitherto been considered a homogeneous cell population. Combined immunocytochemical, anatomical and electrophysiological interrogation of Htr3a-GFP and Nkx2-1-cre:RCE mice revealed that O-LM cells parse into a caudal ganglionic eminence-derived subpopulation expressing 5-HT3A receptors (5-HT(3A)Rs) and a medial ganglionic eminence-derived subpopulation lacking 5-HT(3A)Rs. These two cohorts differentially participate in network oscillations, with 5-HT3AR-containing O-LM cell recruitment dictated by serotonergic tone. Thus, members of a seemingly uniform interneuron population can exhibit unique circuit functions and neuromodulatory properties dictated by disparate developmental origins.
C1 [Chittajallu, Ramesh; Craig, Michael T.; McFarland, Ashley; Yuan, Xiaoqing; Geffen, Scott; Tricoire, Ludovic; Erkkila, Brian; Barron, Sean C.; Lopez, Carla M.; Liang, Barry J.; Jeffries, Brian W.; Pelkey, Kenneth A.; McBain, Chris J.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Dev Neurobiol, NIH, Bethesda, MD USA.
RP Pelkey, KA (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Dev Neurobiol, NIH, Bethesda, MD USA.
EM pelkeyk2@mail.nih.gov
RI Craig, Michael/E-7070-2011
OI Craig, Michael/0000-0001-8481-6709
FU NICHD
FX We thank D. Abebe for expert technical assistance. We are grateful to S.
Anderson (University of Pennsylvania) and a Fishell (New York
University) for providing the Nkx2-1-cre and the RCE reporter mouse
lines, respectively. The GENSAT BAC-Cre driver line (Htr3a-NO152) mice
were obtained from C. Gerfen (National Institute of Mental Health). We
would also like to thank E. Mann (University of Oxford) for providing
the code for the wavelet analyses. This work was supported by an NICHD
intramural award to C.J.M.
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U2 6
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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 2013
VL 16
IS 11
BP 1598
EP 1607
DI 10.1038/nn.3538
PG 10
WC Neurosciences
SC Neurosciences & Neurology
GA 241YX
UT WOS:000326205700017
PM 24097043
ER
PT J
AU Sarkar, C
Chandra, G
Peng, SY
Zhang, ZJ
Liu, AY
Mukherjee, AB
AF Sarkar, Chinmoy
Chandra, Goutam
Peng, Shiyong
Zhang, Zhongjian
Liu, Aiyi
Mukherjee, Anil B.
TI Neuroprotection and lifespan extension in Ppt1(-/-) mice by NtBuHA:
therapeutic implications for INCL
SO NATURE NEUROSCIENCE
LA English
DT Article
ID NEURONAL CEROID-LIPOFUSCINOSIS; PALMITOYL-PROTEIN THIOESTERASE; ENZYME
REPLACEMENT THERAPY; MOUSE MODEL; LYSOSOMAL STORAGE; HYDROXYLAMINE;
ACTIVATION; EXPRESSION; BRAIN; NEURODEGENERATION
AB Infantile neuronal ceroid lipofuscinosis (INCL) is a devastating childhood neurodegenerative lysosomal storage disease (LSD) that has no effective treatment. It is caused by inactivating mutations in the palmitoyl-protein thioesterase-1 (PPT1) gene. PPT1 deficiency impairs the cleavage of thioester linkage in palmitoylated proteins (constituents of ceroid), preventing degradation by lysosomal hydrolases. Consequently, accumulation of lysosomal ceroid leads to INCL. Thioester linkage is cleaved by nucleophilic attack. Hydroxylamine, a potent nucleophilic cellular metabolite, may have therapeutic potential for INCL, but its toxicity precludes clinical application. We found that a hydroxylamine derivative, N-(tert-Butyl) hydroxylamine (NtBuHA), was non-toxic, cleaved thioester linkage in palmitoylated proteins and mediated lysosomal ceroid depletion in cultured cells from INCL patients. In Ppt1(-/-) mice, which mimic INCL, NtBuHA crossed the blood-brain barrier, depleted lysosomal ceroid, suppressed neuronal apoptosis, slowed neurological deterioration and extended lifespan. Our findings provide a proof of concept that thioesterase-mimetic and antioxidant small molecules such as NtBuHA are potential drug targets for thioesterase deficiency diseases such as INCL.
C1 [Sarkar, Chinmoy; Chandra, Goutam; Peng, Shiyong; Zhang, Zhongjian; Mukherjee, Anil B.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Dev Genet, Program Dev Endocrinol & Genet, NIH, Bethesda, MD USA.
[Liu, Aiyi] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biostat & Bioinformat Branch, NIH, Bethesda, MD USA.
RP Mukherjee, AB (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Dev Genet, Program Dev Endocrinol & Genet, NIH, Bethesda, MD USA.
EM mukherja@exchange.nih.gov
RI Peng, Shiyong/D-6391-2014;
OI Peng, Shiyong/0000-0003-0697-3674; Liu, Aiyi/0000-0002-6618-5082
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development
FX We thank S.L. Hofmann (University of Texas Southwestern Medical Center)
for the generous gift of Ppt1-/- mice and for a sample of
recombinant human PPT1 enzyme that we used as a positive control. M.
Sands (Washington University School of Medicine) provided a pair of C57
congenic Ppt1-/- mice that we used to establish our colony at
the US National Institutes of Health. We thank S.W. Levin, J.Y. Chou and
I. Owens for critical review of the manuscript and helpful suggestions.
We also thank A. Bouchelion and A. Chen for editorial assistance. We
thank L. Dye at the Microscopy and Imaging Core facility for his expert
assistance in performing TEM of cultured lymphoblasts and mouse brain
tissues. We are grateful to H.-S. fun for helping us with the FACS
analysis. The mass spectrometric analyses for the detection of NtBuHA in
brain tissues were performed in the laboratory of A.K. Cheema
(Georgetown University School of Medicine). This research was supported
in whole by the Intramural Research Program of the Eunice Kennedy
Shriver National Institute of Child Health and Human Development.
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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 2013
VL 16
IS 11
BP 1608
EP 1617
DI 10.1038/nn.3526
PG 10
WC Neurosciences
SC Neurosciences & Neurology
GA 241YX
UT WOS:000326205700018
PM 24056696
ER
PT J
AU Jia, JM
Zhao, J
Hu, ZH
Lindberg, D
Li, Z
AF Jia, Jie-Min
Zhao, Jun
Hu, Zhonghua
Lindberg, Daniel
Li, Zheng
TI Age-dependent regulation of synaptic connections by dopamine D2
receptors
SO NATURE NEUROSCIENCE
LA English
DT Article
ID DENDRITIC SPINE DENSITY; CORTICAL PYRAMIDAL NEURONS; ENTORHINAL CORTEX;
ANTIPSYCHOTIC-DRUGS; PREFRONTAL CORTEX; SCHIZOPHRENIA; MECHANISMS;
PHOSPHORYLATION; INHIBITION; PLASTICITY
AB Dopamine D2 receptors (D2R) are G protein-coupled receptors that modulate synaptic transmission and are important for various brain functions, including learning and working memory. Abnormal D2R signaling has been implicated in psychiatric disorders such as schizophrenia. Here we report a new function of D2R in dendritic spine morphogenesis. Activation of D2R reduced spine number via GluN2B- and cAMP-dependent mechanisms in mice. Notably, this regulation occurred only during adolescence. During this period, D2R overactivation caused by mutations in the schizophrenia risk gene Dtnbp1 led to spine deficiency, dysconnectivity in the entorhinal-hippocampal circuit and impairment of spatial working memory. Notably, these defects could be ameliorated by D2R blockers administered during adolescence. Our findings suggest an age-dependent function of D2R in spine development, provide evidence that D2R dysfunction during adolescence impairs neuronal circuits and working memory, and indicate that adolescent interventions to prevent aberrant D2R activity protect against cognitive impairment.
C1 [Jia, Jie-Min; Zhao, Jun; Hu, Zhonghua; Lindberg, Daniel; Li, Zheng] NIMH, Unit Synapse Dev & Plast, US NIH, Bethesda, MD 20892 USA.
RP Li, Z (reprint author), NIMH, Unit Synapse Dev & Plast, US NIH, Bethesda, MD 20892 USA.
EM lizheng2@mail.nih.gov
RI Hu, Zhonghua/J-1169-2016; Jia, Jie-Min/O-1150-2013; Hu,
Zhonghua/F-9493-2014; Li, Zheng/I-8016-2014
OI Hu, Zhonghua/0000-0002-0117-7081; Jia, Jie-Min/0000-0001-8446-3819; Li,
Zheng/0000-0002-2978-2531
FU National Institute of Mental Health [ZIA MH002281]
FX We thank H. Arnheiter (NINDS/NIH) for critical discussion of the
manuscript and E.J. Sherman for editing the manuscript. This work was
supported by the Intramural Research Program of the National Institute
of Mental Health (ZIA MH002281 to Z.L.).
NR 47
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U2 22
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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 2013
VL 16
IS 11
BP 1627
EP 1636
DI 10.1038/nn.3542
PG 10
WC Neurosciences
SC Neurosciences & Neurology
GA 241YX
UT WOS:000326205700020
PM 24121738
ER
PT J
AU Lee, BR
Ma, YY
Huang, YHH
Wang, XS
Otaka, M
Ishikawa, M
Neumann, PA
Graziane, NM
Brown, TE
Suska, A
Guo, CY
Lobo, MK
Sesack, SR
Wolf, ME
Nestler, EJ
Shaham, Y
Schluter, OM
Dong, Y
AF Lee, Brian R.
Ma, Yao-Ying
Huang, Yanhua H.
Wang, Xiusong
Otaka, Mami
Ishikawa, Masago
Neumann, Peter A.
Graziane, Nicholas M.
Brown, Travis E.
Suska, Anna
Guo, Changyong
Lobo, Mary Kay
Sesack, Susan R.
Wolf, Marina E.
Nestler, Eric J.
Shaham, Yavin
Schlueter, Oliver M.
Dong, Yan
TI Maturation of silent synapses in amygdala-accumbens projection
contributes to incubation of cocaine craving
SO NATURE NEUROSCIENCE
LA English
DT Article
ID PERMEABLE AMPA RECEPTORS; NUCLEUS-ACCUMBENS; SYNAPTIC PLASTICITY; DRUG
RELAPSE; REINSTATEMENT MODEL; WITHDRAWAL; EXPOSURE; SEEKING;
SENSITIZATION; TRANSMISSION
AB In rat models of drug relapse and craving, cue-induced cocaine seeking progressively increases after withdrawal from the drug. This 'incubation of cocaine craving' is partially mediated by time-dependent adaptations at glutamatergic synapses in nucleus accumbens (NAc). However, the circuit-level adaptations mediating this plasticity remain elusive. We studied silent synapses, often regarded as immature synapses that express stable NMDA receptors with AMPA receptors being either absent or labile, in the projection from the basolateral amygdala to the NAc in incubation of cocaine craving. Silent synapses were detected in this projection during early withdrawal from cocaine. As the withdrawal period progressed, these silent synapses became unsilenced, a process that involved synaptic insertion of calcium-permeable AMPA receptors (CP-AMPARs). In vivo optogenetic stimulation-induced downregulation of CP-AMPARs at amygdala-to-NAc synapses, which re-silenced some of the previously silent synapses after prolonged withdrawal, decreased incubation of cocaine craving. Our findings indicate that silent synapse-based reorganization of the amygdala-to-NAc projection is critical for persistent cocaine craving and relapse after withdrawal.
C1 [Lee, Brian R.] Scripps Res Inst, Dept Mol Therapeut, Jupiter, FL USA.
[Lee, Brian R.; Brown, Travis E.; Dong, Yan] Washington State Univ, Program Neurosci, Pullman, WA 99164 USA.
[Ma, Yao-Ying; Otaka, Mami; Ishikawa, Masago; Neumann, Peter A.; Graziane, Nicholas M.; Guo, Changyong; Sesack, Susan R.; Dong, Yan] Univ Pittsburgh, Dept Neurosci, Pittsburgh, PA USA.
[Huang, Yanhua H.; Wang, Xiusong] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA USA.
[Suska, Anna; Schlueter, Oliver M.] European Neurosci Inst, Gottingen, Germany.
[Lobo, Mary Kay; Nestler, Eric J.] Mt Sinai Sch Med, Fishberg Dept Neurosci, New York, NY USA.
[Lobo, Mary Kay; Nestler, Eric J.] Mt Sinai Sch Med, Friedman Brain Inst, New York, NY USA.
[Wolf, Marina E.] Rosalind Franklin Univ Med & Sci, Dept Neurosci, N Chicago, IL USA.
[Shaham, Yavin] NIDA, Behav Neurosci Branch, Intramural Res Program, US NIH, Baltimore, MD USA.
RP Dong, Y (reprint author), Washington State Univ, Program Neurosci, Pullman, WA 99164 USA.
EM yandong@pitt.edu
RI shaham, yavin/G-1306-2014; dong, yan/J-2859-2014; Lobo, Mary
Kay/K-7734-2015; Dong, Yan/A-4154-2016; Huang, Yanhua/P-1583-2015;
Beroun, Anna/P-6322-2016;
OI Lobo, Mary Kay/0000-0002-9419-2079; Dong, Yan/0000-0003-0016-9028;
Huang, Yanhua/0000-0003-1770-0196; Beroun, Anna/0000-0003-4376-5241;
Lee, Brian/0000-0002-3210-5638
FU National Institute on Drug Abuse [DA028020, DA029565, DA036303,
DA030379, DA009621, DA029099, DA007359, DA014133, DA023206, DA031551,
DA034856]; German Research Foundation through the Cluster of Excellence
"Nanoscale Microscopy and Molecular Physiology of the Brain"; Gottingen
University Medical School; Max Planck Society; [SCHL592/4]
FX We thank B. Sorg, D. Dietz, R.L. Brown and H. Jansen for technical
consultations. This research was supported by the Intramural Research
Program of the National Institute on Drug Abuse (Y.S.), extramural funds
DA028020 (B.R.L.), DA029565 and DA036303 (Y.H.H.), DA030379 (M.E.W. and
Y.D.), DA009621 and DA029099 (M.E.W.), DA007359 and DA014133 (E.J.N.),
DA023206, DA031551 and DA034856 (Y.D.) from the National Institute on
Drug Abuse, the German Research Foundation through the Cluster of
Excellence "Nanoscale Microscopy and Molecular Physiology of the Brain"
and grant SCHL592/4 (O.M.S.). The European Neuroscience Institute
Gottingen is jointly funded by the Gottingen University Medical School
and the Max Planck Society.
NR 50
TC 74
Z9 74
U1 1
U2 22
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 2013
VL 16
IS 11
BP 1644
EP 1651
DI 10.1038/nn.3533
PG 8
WC Neurosciences
SC Neurosciences & Neurology
GA 241YX
UT WOS:000326205700022
PM 24077564
ER
PT J
AU Justinova, Z
Mascia, P
Wu, HQ
Secci, ME
Redhi, GH
Panlilio, LV
Scherma, M
Barnes, C
Parashos, A
Zara, T
Fratta, W
Solinas, M
Pistis, M
Bergman, J
Kangas, BD
Ferre, S
Tanda, G
Schwarcz, R
Goldberg, SR
AF Justinova, Zuzana
Mascia, Paola
Wu, Hui-Qiu
Secci, Maria E.
Redhi, Godfrey H.
Panlilio, Leigh V.
Scherma, Maria
Barnes, Chanel
Parashos, Alexandra
Zara, Tamara
Fratta, Walter
Solinas, Marcell
Pistis, Marco
Bergman, Jack
Kangas, Brian D.
Ferre, Sergi
Tanda, Gianluigi
Schwarcz, Robert
Goldberg, Steven R.
TI Reducing cannabinoid abuse and preventing relapse by enhancing
endogenous brain levels of kynurenic acid
SO NATURE NEUROSCIENCE
LA English
DT Article
ID NICOTINIC ACETYLCHOLINE-RECEPTORS; VENTRAL TEGMENTAL AREA;
NUCLEUS-ACCUMBENS; 3-MONOOXYGENASE INHIBITION; SYNAPTIC-TRANSMISSION;
GLUTAMATE RELEASE; MAMMALIAN BRAIN; WORKING-MEMORY; BINDING-SITES;
DOPAMINE
AB In the reward circuitry of the brain, alpha-7-nicotinic acetylcholine receptors (alpha 7nAChRs) modulate effects of Delta(9)-tetrahydrocannabinol (THC), marijuana's main psychoactive ingredient. Kynurenic acid (KYNA) is an endogenous negative allosteric modulator of alpha 7nAChRs. Here we report that the kynurenine 3-monooxygenase (KMO) inhibitor Ro 61-8048 increases brain KYNA levels and attenuates cannabinoid-induced increases in extracellular dopamine in reward-related brain areas. In the self-administration model of drug abuse, Ro 61-8048 reduced the rewarding effects of THC and the synthetic cannabinoid WIN 55,212-2 in squirrel monkeys and rats, respectively, and it also prevented relapse to drug-seeking induced by reexposure to cannabinoids or cannabinoid-associated cues. The effects of enhancing endogenous KYNA levels with Ro 61-8048 were prevented by positive allosteric modulators of alpha 7nAChRs. Despite a clear need, there are no medications approved for treatment of marijuana dependence. Modulation of KYNA offers a pharmacological strategy for achieving abstinence from marijuana and preventing relapse.
C1 [Justinova, Zuzana; Mascia, Paola; Secci, Maria E.; Redhi, Godfrey H.; Panlilio, Leigh V.; Barnes, Chanel; Parashos, Alexandra; Goldberg, Steven R.] NIDA, Preclin Pharmacol Sect, Behav Neurosci Res Branch, Intramural Res Program,NIH,Dept Hlth & Human Serv, Baltimore, MD USA.
[Justinova, Zuzana; Wu, Hui-Qiu; Schwarcz, Robert] Univ Maryland, Sch Med, Dept Psychiat, Maryland Psychiat Res Ctr, Baltimore, MD 21201 USA.
[Scherma, Maria; Zara, Tamara; Fratta, Walter; Pistis, Marco] Univ Cagliari, Dept Biomed Sci, Sect Neurosci & Clin Pharmacol, Monserrato, Italy.
[Solinas, Marcell] INSERM, U1084, Expt & Clin Neurosci Lab, Neurobiol & Neuropharmacol Addict Grp, Poitiers, France.
[Solinas, Marcell] Univ Poitiers, Poitiers, France.
[Pistis, Marco] CNR, Neurosci Inst, Cagliari, Italy.
[Bergman, Jack; Kangas, Brian D.] Harvard Univ, Sch Med, McLean Hosp, Belmont, MA 02178 USA.
[Ferre, Sergi] NIDA, Integrat Neurobiol Sect, Mol Targets & Medicat Discovery Branch, Intramural Res Program,NIH,Dept Hlth & Human Serv, Baltimore, MD USA.
[Tanda, Gianluigi] NIDA, Psychobiol Sect, Mol Targets & Medicat Discovery Branch, Intramural Res Program,NIH,Dept Hlth & Human Serv, Baltimore, MD USA.
RP Goldberg, SR (reprint author), NIDA, Preclin Pharmacol Sect, Behav Neurosci Res Branch, Intramural Res Program,NIH,Dept Hlth & Human Serv, Baltimore, MD USA.
EM sgoldber@mail.nih.gov
RI Pistis, Marco/A-3773-2013; Ferre, Sergi/K-6115-2014; Justinova,
Zuzana/A-9109-2011; Tanda, Gianluigi/B-3318-2009; Solinas,
Marcello/M-3500-2016
OI Pistis, Marco/0000-0002-4622-3205; Ferre, Sergi/0000-0002-1747-1779;
Justinova, Zuzana/0000-0001-5793-7484; Tanda,
Gianluigi/0000-0001-9526-9878; Solinas, Marcello/0000-0002-0664-5964
FU National Institute on Drug Abuse (NIDA), National Institutes of Health,
Department of Health and Human Services, NIDA Residential Research
Support Services [N01 DA59909]; Italian Ministry of University and
Scientific Research [DA023142, DA035974]; Maryland Psychiatric Research
Center, Department of Psychiatry, University of Maryland School of
Medicine; Regione Autonoma della Sardegna; European Social Fund [LR7
2007]
FX We thank E. Thorndike for excellent technical assistance during the
rodent studies. We thank I. Baum, S. Stevens and P. White for excellent
veterinary assistance during the primate studies. This study was
supported in part by the Intramural Research Program of the National
Institute on Drug Abuse (NIDA), National Institutes of Health,
Department of Health and Human Services, NIDA Residential Research
Support Services Contract N01 DA59909 (principal investigator D. Kelly),
by the Italian Ministry of University and Scientific Research, by
DA023142 (J.B.) and DA035974 (B.D.K.) and by the Maryland Psychiatric
Research Center, Department of Psychiatry, University of Maryland School
of Medicine. T.Z. was supported by a Grant from Regione Autonoma della
Sardegna and by the European Social Fund, LR7 2007.
NR 50
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U1 2
U2 12
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1097-6256
EI 1546-1726
J9 NAT NEUROSCI
JI Nat. Neurosci.
PD NOV
PY 2013
VL 16
IS 11
BP 1652
EP 1661
DI 10.1038/nn.3540
PG 10
WC Neurosciences
SC Neurosciences & Neurology
GA 241YX
UT WOS:000326205700023
PM 24121737
ER
PT J
AU Linehan, WM
Srinivasan, R
AF Linehan, W. Marston
Srinivasan, Ramaprasad
TI TARGETED THERAPIES Treating advanced kidney cancer-miles to go before we
sleep
SO NATURE REVIEWS CLINICAL ONCOLOGY
LA English
DT Editorial Material
ID RENAL-CELL CARCINOMA
AB A randomized phase III trial comparing pazopanib with sunitinib in patients with advanced clear cell renal cell carcinoma showed that although progression-free survival and overall survival were similar, pazopanib was better tolerated. Recent advances in genomics and metabolomics have provided novel insights that could be leveraged to improve therapy.
C1 [Linehan, W. Marston; Srinivasan, Ramaprasad] NCI, Urol Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Linehan, WM (reprint author), NCI, Urol Oncol Branch, Ctr Canc Res, CRC Room 1W-5940, Bethesda, MD 20892 USA.
EM wml@nih.gov
FU Intramural NIH HHS [ZIA BC011038-06, ZIA BC011028-06]
NR 10
TC 4
Z9 4
U1 0
U2 6
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1759-4774
EI 1759-4782
J9 NAT REV CLIN ONCOL
JI Nat. Rev. Clin. Oncol.
PD NOV
PY 2013
VL 10
IS 11
BP 614
EP 615
DI 10.1038/nrclinonc.2013.183
PG 2
WC Oncology
SC Oncology
GA 243NM
UT WOS:000326323100005
PM 24129349
ER
PT J
AU Schetter, CD
Schafer, P
Lanzi, RG
Clark-Kauffman, E
Raju, TNK
Hillemeier, MM
AF Schetter, Christine Dunkel
Schafer, Peter
Lanzi, Robin Gaines
Clark-Kauffman, Elizabeth
Raju, Tonse N. K.
Hillemeier, Marianne M.
CA Community Child Hlth Network
TI Shedding Light on the Mechanisms Underlying Health Disparities Through
Community Participatory Methods: The Stress Pathway
SO PERSPECTIVES ON PSYCHOLOGICAL SCIENCE
LA English
DT Review
DE stress; health disparities; socioeconomic status (SES); ethnicity
ID ADVERSE BIRTH OUTCOMES; PRENATAL PSYCHOSOCIAL PROFILE; INTIMATE PARTNER
VIOLENCE; SOCIOECONOMIC-STATUS; PHYSICAL HEALTH; UNITED-STATES; LIFE
EVENTS; PERCEIVED STRESS; PRETERM BIRTH; PSYCHOLOGICAL STRESS
AB Health disparities are large and persistent gaps in the rates of disease and death between racial/ethnic and socioeconomic status subgroups in the population. Stress is a major pathway hypothesized to explain such disparities. The Eunice Kennedy Shriver National Institute of Child Health and Human Development formed a community/research collaborativethe Community Child Health Networkto investigate disparities in maternal and child health in five high-risk communities. Using community participation methods, we enrolled a large cohort of African American/Black, Latino/Hispanic, and non-Hispanic/White mothers and fathers of newborns at the time of birth and followed them over 2 years. A majority had household incomes near or below the federal poverty level. Home interviews yielded detailed information regarding multiple types of stress such as major life events and many forms of chronic stress including racism. Several forms of stress varied markedly by racial/ethnic group and income, with decreasing stress as income increased among Caucasians but not among African Americans; other forms of stress varied by race/ethnicity or poverty alone. We conclude that greater sophistication in studying the many forms of stress and community partnership is necessary to uncover the mechanisms underlying health disparities in poor and ethnic-minority families and to implement community health interventions.
C1 [Schetter, Christine Dunkel] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90095 USA.
[Schafer, Peter] New York Acad Sci, New York, NY USA.
[Lanzi, Robin Gaines] Univ Alabama Birmingham, Dept Hlth Behav, Birmingham, AL USA.
[Clark-Kauffman, Elizabeth] North Shore Univ Hlth Syst, Sect Child & Family Hlth Studies, Evanston, IL USA.
[Raju, Tonse N. K.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Natl Inst Hlth, Pregnancy & Perinatol Branch, Rockville, MD USA.
[Hillemeier, Marianne M.] Penn State Univ, Dept Hlth Policy & Adm, University Pk, PA 16802 USA.
RP Schetter, CD (reprint author), Univ Calif Los Angeles, Dept Psychol, 1285A Franz Hall, Los Angeles, CA 90095 USA.
EM dunkel@psych.ucla.edu
NR 117
TC 13
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U1 11
U2 35
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 1745-6916
EI 1745-6924
J9 PERSPECT PSYCHOL SCI
JI Perspect. Psychol. Sci.
PD NOV
PY 2013
VL 8
IS 6
BP 613
EP 633
DI 10.1177/1745691613506016
PG 21
WC Psychology, Multidisciplinary
SC Psychology
GA 246KV
UT WOS:000326537700002
ER
PT J
AU Petrov, MER
Kim, Y
Lauderdale, D
Lewis, CE
Reis, JP
Carnethon, MR
Knutson, K
Glasser, SJ
AF Petrov, Megan E. Ruiter
Kim, Yongin
Lauderdale, Diane
Lewis, Cora E.
Reis, Jared P.
Carnethon, Mercedes R.
Knutson, Kristen
Glasser, Stephen J.
TI Longitudinal Associations between Objective Sleep and Lipids: The CARDIA
Study
SO SLEEP
LA English
DT Article
DE Sleep duration; sleep fragmentation; lipids; sleep quality; ethnicity;
sex
ID DENSITY-LIPOPROTEIN-CHOLESTEROL; CARDIOVASCULAR-DISEASE RISK; METABOLIC
SYNDROME; BLOOD-PRESSURE; NATIONAL-HEALTH; FOLLOW-UP; DURATION; WOMEN;
MORTALITY; HYPERTENSION
AB Study Objective: To investigate the longitudinal relationships between actigraph-derived sleep duration, fragmentation, and lipid levels.
Design and Setting: Longitudinal data from the Coronary Artery Risk Development in Young Adults Sleep Study (2003-05), an observational cohort at the Chicago site.
Participants: There were 503 black and white adults, ages 32-51 years, with no prior history of cardiovascular disease.
Interventions: N/A.
Measurement and Results: Sleep duration and fragmentation were measured using 6 days of wrist actigraphy. Sleep quality was measured with the Pittsburgh Sleep Quality Index. The outcome variables, measured at 3 examinations over 10 years (Baseline [2000-01], 5-year [2005-06], and 10-year follow-up [2010-11]), were total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides (TG), and TC/HDL ratio. The associations between each sleep parameter and 10-year change in lipids were analyzed with generalized estimating equation models adjusting for relevant confounders. After adjustment, each hour increase in sleep duration was significantly associated with higher TC (5.2 mg/dL, 95%CI: 1.7, 8.6) and LDL (3.4 mg/dL, 95%CI: 0.2, 6.6) in the total sample, a 1.1 mg/dL increase in TG (95%CI: 1.0, 1.1) among men, and a borderline significant greater odds for a TC/HDL ratio >= 5 among men (OR: 1.37, 95%CI: 0.99, 1.90). Overall, sleep fragmentation and sleep quality scores were not associated with change in lipids.
Conclusions: Beyond relevant covariates, over a 10-year follow-up, longer objective sleep duration was longitudinally and significantly associated with a poorer lipid profile. Greater objective sleep fragmentation and self-reported poor sleep quality were not related to a poorer lipid profile.
C1 [Petrov, Megan E. Ruiter] Arizona State Univ, Coll Nursing & Hlth Innovat, Phoenix, AZ 85004 USA.
[Kim, Yongin; Lewis, Cora E.; Glasser, Stephen J.] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA.
[Lauderdale, Diane; Knutson, Kristen] Univ Chicago, Dept Med, Chicago, IL 60637 USA.
[Reis, Jared P.] NHLBI, Div Cardiovasc Sci, Bethesda, MD 20892 USA.
[Carnethon, Mercedes R.] Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA.
RP Petrov, MER (reprint author), Arizona State Univ, Coll Nursing & Hlth Innovat, 500 N 3rd St, Phoenix, AZ 85004 USA.
EM Megan.Petrov@asu.edu
OI Knutson, Kristen/0000-0002-2751-6168
FU Novo Nordisk; AMGON; US Public Health Service [NO1-HC-48047,
NO1-HC-48048, NO1-HC-48049, NO1-HC-48050]; National Heart, Lung, and
Blood Institute [NO1-HC-95095]; National Institute on Aging [AG 11412]
FX This was not an industry supported study. Poster presented at the
Academy Health 2012 Annual Research Meeting, Orlando, FL, 6/25/2012. Dr.
Petrov receives training support from AHRQ (5 T32 HS013852-09) and NCMHD
(3 P60 MD000502-08S1). Dr. Lewis receives funding from Novo Nordisk. Dr.
Glasser receives salary support from AMGON. The other authors have
indicated no financial conflicts of interest. CARDIA is supported by US
Public Health Service contracts NO1-HC-48047, NO1-HC-48048,
NO1-HC-48049, NO1-HC-48050, and NO1-HC-95095 from the National Heart,
Lung, and Blood Institute, and grant AG 11412 from the National
Institute on Aging. Yongin Kim had full access to the data and is
responsible for the data analyses presented.
NR 46
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U1 0
U2 4
PU AMER ACAD SLEEP MEDICINE
PI WESTCHESTER
PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA
SN 0161-8105
EI 1550-9109
J9 SLEEP
JI Sleep
PD NOV 1
PY 2013
VL 36
IS 11
BP 1587
EP 1595
DI 10.5665/sleep.3104
PG 9
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 246KW
UT WOS:000326537800002
PM 24179290
ER
PT J
AU Endeshaw, Y
Rice, TB
Schwartz, AV
Stone, KL
Manini, TM
Satterfield, S
Cummings, S
Harris, T
Pahor, M
AF Endeshaw, Yohannes
Rice, Thomas B.
Schwartz, Ann V.
Stone, Katie L.
Manini, Todd M.
Satterfield, Suzanne
Cummings, Steven
Harris, Tamara
Pahor, Marco
CA Hlth ABC Study
TI Snoring, Daytime Sleepiness, and Incident Cardiovascular Disease in The
Health, Aging, and Body Composition Study
SO SLEEP
LA English
DT Article
DE Snoring; daytime sleepiness; cardiovascular disease
ID CORONARY-HEART-DISEASE; 6-YEAR FOLLOW-UP; OLDER-ADULTS; RISK-FACTORS;
APNEA; POPULATION; MORTALITY; HYPERTENSION; WOMEN; AGE
AB Objectives: To examine the association between snoring and incident cardiovascular disease (CVD).
Design, Settings, and Participants: This is a prospective study in which community dwelling older adults were evaluated at baseline, and followed up for an average of 9.9 years.
Measurements: Data on snoring, daytime sleepiness, as well as demographic and clinical characteristics of study participants was collected at baseline, and participants were followed up every six months for an average of 9.9 years. Based on snoring and sleepiness status, 4 groups of participants were created: (1) No Snoring, No Sleepiness; (2) No Snoring, Sleepiness; (3) Snoring, No Sleepiness; (4) Snoring, Sleepiness. Incident CVD was defined as a diagnosis of myocardial infarction, angina pectoris, or congestive heart failure that resulted in overnight hospitalization during the follow-up period. Cox proportional hazard was used to estimate the risk of incident cardiovascular disease during follow-up by baseline snoring and sleepiness status.
Results: A total of 2,320 participants with a mean age of 73.6 (2.9) years at baseline were included in the analysis. Fifty-two percent were women, and 58% were white. A total of 543 participants developed CVD events during the follow-up period. Participants who reported snoring associated with daytime sleepiness had significantly increased hazard ratio for CVD events (HR = 1.46 [1.03-2.08], P = 0.035) after adjusting for demographic and clinical confounding factors.
Conclusion: The results suggest that self-reported snoring and daytime sleepiness status are associated with an increased risk of future cardiovascular disease among older adults.
C1 [Endeshaw, Yohannes] Morehouse Sch Med, Dept Med, Atlanta, GA 30310 USA.
[Rice, Thomas B.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA.
[Schwartz, Ann V.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
[Stone, Katie L.; Cummings, Steven] Calif Pacific Med Ctr, Res Inst, San Francisco, CA USA.
[Manini, Todd M.; Pahor, Marco] Univ Florida, Coll Med, Dept Aging & Geriatr Res, Gainesville, FL USA.
[Satterfield, Suzanne] Univ Tennessee, Dept Prevent Med, Memphis, TN USA.
[Harris, Tamara] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
RP Endeshaw, Y (reprint author), Morehouse Sch Med, Dept Med, Div Geriatr, 720 Westview Dr SW, Atlanta, GA 30310 USA.
EM yendeshaw@msm.edu
FU National Institute of Health (NIH), National Institute on Aging (NIA);
NIA [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106, R01-AG028050]; NINR,
Claude D. Pepper Older Americans Independence Center [R01-NR012459, P30
AG028740]
FX This research was supported in part by the Intramural Research Program
of the National Institute of Health (NIH), National Institute on Aging
(NIA), by NIA contracts N01-AG-6-2101; N01-AG-6-2103; N01-AG-6-2106; NIA
grant R01-AG028050, NINR grant R01-NR012459 and P30 AG028740 Claude D.
Pepper Older Americans Independence Center.
NR 50
TC 12
Z9 12
U1 0
U2 3
PU AMER ACAD SLEEP MEDICINE
PI WESTCHESTER
PA ONE WESTBROOK CORPORATE CTR, STE 920, WESTCHESTER, IL 60154 USA
SN 0161-8105
EI 1550-9109
J9 SLEEP
JI Sleep
PD NOV 1
PY 2013
VL 36
IS 11
BP 1737
EP 1745
DI 10.5665/sleep.3140
PG 9
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 246KW
UT WOS:000326537800020
PM 24179308
ER
PT J
AU Feng, Y
Forsell, MNE
Flynn, B
Adams, W
Lore, K
Seder, R
Wyatt, RT
Hedestam, GBK
AF Feng, Yu
Forsell, Mattias N. E.
Flynn, Barbara
Adams, William
Lore, Karin
Seder, Robert
Wyatt, Richard T.
Hedestam, Gunilla B. Karlsson
TI Chemical cross-linking of HIV-1 Env for direct TLR7/8 ligand conjugation
compromises recognition of conserved antigenic determinants
SO VIROLOGY
LA English
DT Article
DE HIV-1 envelope glycoprotein; Cross-linker; Toll-like receptor ligand;
Neutralizing antibody
ID T-CELL RESPONSES; TOLL-LIKE RECEPTORS; PLASMACYTOID DENDRITIC CELLS;
NAIVE B-CELLS; INNATE IMMUNITY; ANTIBODY-RESPONSES; NONHUMAN-PRIMATES;
INFLUENZA VACCINE; HUMORAL IMMUNITY; ADJUVANTS
AB Covalent conjugation of immune-stimulatory compounds to protein antigens is a potential means to self-adjuvant non-replicating subunit vaccines. Previously, it was demonstrated that covalent coupling of a Toll-like receptor (TLR) ligand to the exterior HIV-1 envelope glycoprotein, gp120, enhanced its immunogenicity. However, the consequences of chemical conjugation to gp120 on broadly neutralizing antibody (bNAb) epitopes were so far not examined. Here, we conjugated a TLR7/8 ligand to lysine residues on gp120 using NHS-PEO8-maleimide linkers and investigated if this affected Ab recognition of the CD4 binding site (CD4bs), a highly conserved target for bNAbs. We demonstrate that the recognition of the CD4bs was reduced following coupling, especially at a higher coupling ratio. These results have implications for the coupling of ligands to vaccine antigens where elicitation of humoral immune responses to specific neutralizing determinants is desired. (C) 2013 Elsevier Inc. All rights reserved.
C1 [Feng, Yu; Forsell, Mattias N. E.; Flynn, Barbara; Seder, Robert; Wyatt, Richard T.] NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA.
[Feng, Yu; Wyatt, Richard T.] Scripps Res Inst, IAVI Ctr Neutralizing Antibodies, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA.
[Adams, William; Lore, Karin] Karolinska Inst, Ctr Infect Med, SE-17177 Stockholm, Sweden.
[Forsell, Mattias N. E.; Hedestam, Gunilla B. Karlsson] Karolinska Inst, Dept Microbiol Tumor & Cell Biol, SE-17177 Stockholm, Sweden.
[Wyatt, Richard T.] Scripps Res Inst, Scripps Ctr HIV AIDS Vaccine Immunol & Immunogen, La Jolla, CA 92037 USA.
RP Wyatt, RT (reprint author), Scripps Res Inst, Scripps Ctr HIV AIDS Vaccine Immunol & Immunogen, La Jolla, CA 92037 USA.
EM wyatt@scripps.edu; Gunilla.Karlsson.Hedestam@ki.se
RI Feng, Yu/A-3396-2012
FU International AIDS Vaccine Initiative; Swedish International Development
Agency/Department of Research Cooperation; Swedish Research Council;
Vaccine Research Center; National Institutes of Health; Karolinska
Institutet; amfAR Mathilde Krim Fellowship in Basic Biomedical Research
[108213-51-RKVA]
FX We thank Christina Corbaci for assistance with the figures. This study
was supported by grants from the International AIDS Vaccine Initiative
(GKH and RW), the Swedish International Development Agency/Department of
Research Cooperation (GKH), the Swedish Research Council (GKH), the
intramural research program of the Vaccine Research Center, the National
Institutes of Health (RW) and by Karolinska Institutet (GKH). MNEF is
supported by amfAR Mathilde Krim Fellowship in Basic Biomedical Research
# 108213-51-RKVA.
NR 41
TC 4
Z9 4
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 2013
VL 446
IS 1-2
BP 56
EP 65
DI 10.1016/j.virol.2013.07.028
PG 10
WC Virology
SC Virology
GA 236ZX
UT WOS:000325839100007
PM 24074567
ER
PT J
AU Alexandre, KB
Moore, PL
Nonyane, M
Gray, ES
Ranchobe, N
Chakauya, E
McMahon, JB
O'Keefe, BR
Chikwamba, R
Morris, L
AF Alexandre, Kabamba B.
Moore, Penny L.
Nonyane, Molati
Gray, Elin S.
Ranchobe, Nthabeleng
Chakauya, Ereck
McMahon, James B.
O'Keefe, Barry R.
Chikwamba, Rachel
Morris, Lynn
TI Mechanisms of HIV-1 subtype C resistance to GRFT, CV-N and SVN
SO VIROLOGY
LA English
DT Article
DE Griffithsin; Cyanovirin-N; Scytovirin; HIV subtype C; Resistance; Entry
inhibitor; Glycans; Single genome amplification; Microbicide
ID HUMAN-IMMUNODEFICIENCY-VIRUS; ENVELOPE GLYCOPROTEIN GP120; ENTRY
INHIBITOR GRIFFITHSIN; CYANOVIRIN-N; ANTIBODY NEUTRALIZATION;
CARBOHYDRATE-BINDING; LINKED GLYCOSYLATION; INACTIVATING PROTEIN; TYPE-1
STRAINS; PLANT-LECTINS
AB We examined the ability of HIV-1 subtype C to develop resistance to the inhibitory lectins, griffithsin (GRFT), cyanovirin-N (CV-N) and scytovirin (SVN), which bind multiple mannose-rich glycans on gp120. Four primary HIV-1 strains cultured under escalating concentrations of these lectins became increasingly resistant tolerating 2 to 12 times their 50% inhibitory concentrations. Sequence analysis of gp120 showed that most had deletions of 1 to 5 mannose-rich glycans. Glycosylation sites at positions 230, 234, 241, 289 located in the C2 region and 339,392 and 448 in the C3-C4 region were affected. Furthermore, deletions and insertions of up to 5 amino acids in the V4 region were observed in 3 of the 4 isolates. These data suggest that loss of glycosylation sites on gp120 as well as rearrangement of glycans in V4 are mechanisms involved in HIV-1 subtype C escape from GRFT, CV-N and SVN. (C) 2013 Elsevier Inc. All rights reserved.
C1 [Alexandre, Kabamba B.; Moore, Penny L.; Nonyane, Molati; Gray, Elin S.; Ranchobe, Nthabeleng; Morris, Lynn] Natl Inst Communicable Dis, Ctr HIV & STIs, ZA-2131 Johannesburg, South Africa.
[Alexandre, Kabamba B.; Moore, Penny L.; Morris, Lynn] Univ Witwatersrand, Johannesburg, South Africa.
[Chakauya, Ereck; Chikwamba, Rachel] CSIR, ZA-0001 Pretoria, South Africa.
[McMahon, James B.; O'Keefe, Barry R.] NCI Frederick, Mol Targets Lab, Ctr Canc Res, Frederick, MD USA.
RP Morris, L (reprint author), Natl Inst Communicable Dis, Ctr HIV & STIs, Private Bag X4, ZA-2131 Johannesburg, South Africa.
EM lynnm@nicd.ac.za
OI Moore, Penny/0000-0001-8719-4028; Gray, Elin/0000-0002-8613-3570
FU BioFISA program of NEPAD Agency/SANBio; Poliomyelitis Research
Foundation; South African AIDS Vaccine Initiative (SAAVI); Columbia
University-Southern African Fogarty AIDS International Training and
Research Programme (AITRP); Fogarty International Center, NIH; NIH,
National Cancer Institute, Center for Cancer Research; Wellcome Trust
[089933/Z/09/Z]
FX This work was funded by the BioFISA program of NEPAD Agency/SANBio under
the microbicide project, the Poliomyelitis Research Foundation, the
South African AIDS Vaccine Initiative (SAAVI) and a training fellowship
to KBA from Columbia University-Southern African Fogarty AIDS
International Training and Research Programme (AITRP) funded by the
Fogarty International Center, NIH. This research was also supported by
the Intramural Research Program of the NIH, National Cancer Institute,
Center for Cancer Research (B. O. & J. M.). Penny Moore is supported by
the Wellcome Trust (Grant 089933/Z/09/Z).
NR 54
TC 10
Z9 10
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 2013
VL 446
IS 1-2
BP 66
EP 76
DI 10.1016/j.virol.2013.07.019
PG 11
WC Virology
SC Virology
GA 236ZX
UT WOS:000325839100008
PM 24074568
ER
PT J
AU Lakdawala, SS
Shih, AR
Jayaraman, A
Lamirande, EW
Moore, I
Paskel, M
Sasisekharan, R
Subbarao, K
AF Lakdawala, Seema S.
Shih, Angela R.
Jayaraman, Akila
Lamirande, Elaine W.
Moore, Ian
Paskel, Myeisha
Sasisekharan, Ram
Subbarao, Kanta
TI Receptor specificity does not affect replication or virulence of the
2009 pandemic H1N1 influenza virus in mice and ferrets
SO VIROLOGY
LA English
DT Article
DE Influenza virus; Tissue tropism; Virulence; Receptor specificity;
Replication
ID BINDING PROPERTIES; RESPIRATORY-TRACT; CROSS-PROTECTION; CELL TROPISM;
HUMAN AIRWAY; A VIRUSES; IN-VIVO; HEMAGGLUTININ; TRANSMISSION; ORIGIN
AB Human influenza viruses predominantly bind alpha 2,6 linked sialic acid (SA) while avian viruses bind alpha 2,3 SA-containing complex glycans. Virulence and tissue tropism of influenza viruses have been ascribed to this binding preference. We generated 2009 pandemic H1N1 (pH1N1) viruses with either predominant alpha 2,3 or alpha 2,6 SA binding and evaluated these viruses in mice and ferrets. The alpha 2,3 pH1N1 virus had similar virulence in mice and replicated to similar titers in the respiratory tract of mice and ferrets as the alpha 2,6 and WT pH1N1 viruses. Immunohistochemical analysis determined that all viruses infected similar cell types in ferret lungs. There is increasing evidence that receptor specificity of influenza viruses is more complex than the binary model of alpha 2,6 and alpha 2,3 SA binding and our data suggest that influenza viruses use a wide range of SA moieties to infect host cells. Published by Elsevier Inc.
C1 [Lakdawala, Seema S.; Shih, Angela R.; Lamirande, Elaine W.; Moore, Ian; Paskel, Myeisha; Subbarao, Kanta] Natl Inst Hlth, Natl Inst Allergy & Infect Dis, Infect Dis Lab, Bethesda, MD 20892 USA.
[Jayaraman, Akila; Sasisekharan, Ram] MIT, Singapore MIT Alliance Res & Technol, Koch Inst Integrat Canc Res, Dept Biol Engn, Cambridge, MA USA.
RP Sasisekharan, R (reprint author), MIT, Singapore MIT Alliance Res & Technol, Koch Inst Integrat Canc Res, Dept Biol Engn, Cambridge, MA USA.
EM rams@MIT.edu; ksubbarao@niaid.nih.gov
FU Intramural Research Program of the National Institute of Allergy and
Infectious Diseases (NIAID); National Institutes of Health (NIH);
National Institutes of Health [R37 GM057073-13]; Singapore-MIT Alliance
for Research and Technology (SMART)
FX We thank the Comparative Medical Branch of NIAID for technical
assistance during the animal studies and members of the Subbarao lab for
critical review of the manuscript. This work was supported by the
Intramural Research Program of the National Institute of Allergy and
Infectious Diseases (NIAID), National Institutes of Health (NIH) and was
funded in part by the National Institutes of Health (R37 GM057073-13 to
RS) and in part by Singapore-MIT Alliance for Research and Technology
(SMART to RS). The viruses generated in this manuscript could
potentially alter the host range of the 2009 pandemic H1N1 influenza
virus; therefore, our manuscript was reviewed by the NIH's Intramural
Research Program's Committee on Dual Use Research of Concern (DURC). The
committee concluded that the methods and results reported in our
manuscript do not meet DURC criteria.
NR 51
TC 9
Z9 10
U1 0
U2 7
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0042-6822
J9 VIROLOGY
JI Virology
PD NOV
PY 2013
VL 446
IS 1-2
BP 349
EP 356
DI 10.1016/j.virol.2013.08.011
PG 8
WC Virology
SC Virology
GA 236ZX
UT WOS:000325839100039
PM 24074599
ER
PT J
AU Yu, L
Takeda, K
Markoff, L
AF Yu, Li
Takeda, Kazuyo
Markoff, Lewis
TI Protein-protein interactions among West Nile non-structural proteins and
transmembrane complex formation in mammalian cells
SO VIROLOGY
LA English
DT Article
DE NS protein interactions; Transmembrane complex; Flavivirus replication
complex
ID DEPENDENT RNA-POLYMERASE; DENGUE-VIRUS TYPE-2; HEPATITIS-C VIRUS;
FLAVIVIRUS KUNJIN; FLUORESCENCE COMPLEMENTATION; ENDOPLASMIC-RETICULUM;
REPLICATION COMPLEX; SECONDARY STRUCTURE; LIVING CELLS; POLYCLONAL
ANTISERA
AB To study the membrane orientation of flavivirus non-structural proteins (NSPs) in the replication complex, the seven major West Nile (WN) NSPs were separately expressed in monkey cells, and their subcellular localization was investigated by imaging-based techniques. First, we observed by confocal microscopy that four small transmembrane proteins (TP) (NS2A, NS2B, NS4A, and NS4B) were located to the endoplasmic reticulum (ER), whereas the largest NSPs, NS1, NS3, and NS5 were not. We then analyzed the colocalization and the association of WN NSPs using the methods of confocal microscopy, fluorescence resonance energy transfer (FRET), and biologic fluorescence complementation (BiFC). Through these combined imaging techniques, protein-protein interactions (PPI) among WNNSPs were detected. Our data demonstrate that there are interactions between NS2A and NS4A, and interactions of NS2B with three other TPs (NS2A, NS4A, and NS4B) as well as the expected interaction with NS3. PPI between NS2A and NS4B or between NS4A and NS4B were not detected. By the criteria of these techniques, NS5 interacted only with NS3, and NS1 was not shown to be in close proximity with other NSPs. In addition, homo-oligomerization of some NSPs was observed and three-way interactions between NS2A, NS4A, and NA4B with NS2B-NS3 were also observed, respectively. Our results suggest that the four TPs are required for formation of transmembrane complex. NS2B protein seems to play a key role in bringing the TPs together on the ER membrane and in bridging the TPs with non-membrane-associated proteins (NS3 and NS5). Published by Elsevier Inc.
C1 [Yu, Li; Markoff, Lewis] FDA, CBER, Microscopy & Imaging Core Facil, Off Vaccines Res & Review,Div Viral Prod,Lab Vect, Bethesda, MD USA.
[Takeda, Kazuyo] FDA, CBER, Microscopy & Imaging Core Facil, Bethesda, MD USA.
RP Yu, L (reprint author), Bg 29A,Room 1B18,NIH Campus,8800 Rockville Pike, Bethesda, MD 20892 USA.
EM li.yu@fda.hhs.gov
NR 78
TC 17
Z9 17
U1 3
U2 18
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0042-6822
J9 VIROLOGY
JI Virology
PD NOV
PY 2013
VL 446
IS 1-2
BP 365
EP 377
DI 10.1016/j.virol.2013.08.006
PG 13
WC Virology
SC Virology
GA 236ZX
UT WOS:000325839100041
PM 24074601
ER
PT J
AU Makrogiannis, S
Caturegli, G
Davatzikos, C
Ferrucci, L
AF Makrogiannis, Sokratis
Caturegli, Giorgio
Davatzikos, Christos
Ferrucci, Luigi
TI Computer-aided Assessment of Regional Abdominal Fat with Food Residue
Removal in CT
SO ACADEMIC RADIOLOGY
LA English
DT Article
DE Body composition assessment; false positive reduction
ID ADIPOSITY; QUANTIFICATION; REGISTRATION; ASSOCIATION; TOMOGRAPHY;
NETWORKS; WAVELETS; IMAGES; HEALTH
AB Rationale and Objectives: Separate quantification of abdominal subcutaneous and visceral fat regions is essential to understand the role of regional adiposity as risk factor in epidemiological studies. Fat quantification is often based on computed tomography (CT) because fat density is distinct from other tissue densities in the abdomen. However, the presence of intestinal food residues with densities similar to fat may reduce fat quantification accuracy. We introduce an abdominal fat quantification method in CT with interest in food residue removal.
Materials and Methods: Total fat was identified in the feature space of Hounsfield units and divided into subcutaneous and visceral components using model-based segmentation. Regions of food residues were identified and removed from visceral fat using a machine learning method integrating intensity, texture, and spatial information. Cost-weighting and bagging techniques were investigated to address class imbalance.
Results: We validated our automated food residue removal technique against semimanual quantifications. Our feature selection experiments indicated that joint intensity and texture features produce the highest classification accuracy at 95%. We explored generalization capability using k-fold cross-validation and receiver operating characteristic (ROC) analysis with variable k. Losses in accuracy and area under ROC curve between maximum and minimum k were limited to 0.1% and 0.3%. We validated tissue segmentation against reference semimanual delineations. The Dice similarity scores were as high as 93.1 for subcutaneous fat and 85.6 for visceral fat.
Conclusions: Computer-aided regional abdominal fat quantification is a reliable computational tool for large-scale epidemiological studies. Our proposed intestinal food residue reduction scheme is an original contribution of this work. Validation experiments indicate very good accuracy and generalization capability.
C1 [Makrogiannis, Sokratis; Caturegli, Giorgio; Ferrucci, Luigi] Natl Inst Hlth, Natl Inst Aging, Longitudinal Studies Sect, Baltimore, MD 21225 USA.
[Davatzikos, Christos] Univ Penn, Dept Radiol, Sect Biomed Image Anal, Philadelphia, PA 19104 USA.
[Makrogiannis, Sokratis] Delaware State Univ, Dept Math Sci, Dover, DE 19901 USA.
RP Makrogiannis, S (reprint author), Natl Inst Hlth, Natl Inst Aging, Longitudinal Studies Sect, 3001 South Hanover St 5th Fl, Baltimore, MD 21225 USA.
EM makrogianniss@mail.nih.gov
FU Intramural Research Program of the National Institutes of Health,
National Institute on Aging
FX This research was supported entirely by the Intramural Research Program
of the National Institutes of Health, National Institute on Aging. We
also thank Dr. Ramona Ramachandran for producing reference masks of
visceral fat and food residue regions.
NR 30
TC 6
Z9 6
U1 1
U2 5
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1076-6332
EI 1878-4046
J9 ACAD RADIOL
JI Acad. Radiol.
PD NOV
PY 2013
VL 20
IS 11
BP 1413
EP 1421
DI 10.1016/j.acra.2013.08.007
PG 9
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 241AW
UT WOS:000326139800012
PM 24119354
ER
PT J
AU Chuang, ML
Leslie, RW
Massaro, JM
Manders, ES
Fox, CS
Hoffmann, U
O'Donnell, CJ
AF Chuang, Michael L.
Leslie, Richard W.
Massaro, Joseph M.
Manders, Emily S.
Fox, Caroline S.
Hoffmann, Udo
O'Donnell, Christopher J.
TI Distribution of Abdominal Aortic Calcium by Computed Tomography: Impact
of Analysis Method on Quantitative Calcium Score
SO ACADEMIC RADIOLOGY
LA English
DT Article
DE Abdominal aorta; calcium; population study; segment length; computed
tomography
ID CORONARY-ARTERY CALCIUM; HEART; ATHEROSCLEROSIS; CALCIFICATION;
PREDICTOR; QUANTIFICATION; MORTALITY; COHORT; CT
AB Rationale and Objectives: Abdominal aortic calcification (MC) can be quantified using computed tomography (CT), but imaging planes are prescribed based on bony landmarks, so that individual variation between the landmark and the aortoiliac junction can result in variable aortic coverage. In the Framingham CT substudy, we scanned a 15-cm (Z-direction) abdominal segment cranial to the Si vertebral body. We sought to determine the range and distribution of length of aorta scanned and the distribution of AAC within the abdominal aorta and to compare burden of AAC measured from fixed-length segments versus MC from all slices cranial to the aortoiliac bifurcation.
Materials and Methods: MC was quantified by modified Agatston score (AS) in 100 Framingham Heart Study participants (60 13 years old, 51 men). We compared the AS measured from 5-cm and 8-cm segments with the AS(ALL) (total visualized aorta).
Results: Of 100, 73 participants had MC >0. The total length of aorta imaged was >= 8 cm in 84% of participants. Qualitatively, 5-cm and 8-cm segments correctly identified 96% and 99%, respectively, of participants as having or not having MC. Quantitatively, AS(8cm) was within 20% of AS(ALL) in four-fifths and within 30% of AS(ALL) in nine-tenths of participant. AS(5cm) more severely underestimated AS(ALL).
Conclusion: The use of 51 as the caudal imaging landmark in a 15-cm slab yields >= 8 cm aortic coverage in most adults. Both 5-cm and 8-cm analysis strategies are comparable to analyzing the total visualized abdominal aorta for prevalent MC, but only 8-cm segment analysis yields quantitatively similar measures of AAC.
C1 [Chuang, Michael L.; Leslie, Richard W.; Massaro, Joseph M.; Manders, Emily S.; Fox, Caroline S.; O'Donnell, Christopher J.] Natl Heart Lung & Blood Inst, Framingham Heart Study, Framingham, MA 01702 USA.
[Massaro, Joseph M.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Fox, Caroline S.] Brigham & Womens Hosp, Div Endocrinol Diabet & Hypertens, Boston, MA USA.
[Hoffmann, Udo] Massachusetts Gen Hosp, Dept Radiol, Cardiac MR PET & CT Program, Boston, MA 02114 USA.
[O'Donnell, Christopher J.] Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA.
[Fox, Caroline S.; Hoffmann, Udo; O'Donnell, Christopher J.] Harvard Univ, Sch Med, Boston, MA USA.
RP O'Donnell, CJ (reprint author), Natl Heart Lung & Blood Inst, Framingham Heart Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA.
EM odonnellc@nhlbi.nih.gov
FU National Heart, Lung, and Blood Institute (NHLBI) Framingham Heart Study
[N01-HC-25195, N01-HC-38038]; NHLBI Division of Intramural Research
FX From the National Heart, Lung, and Blood Institute, The Framingham Heart
Study, 73 Mt Wayte Avenue, Suite No. 2, Framingham, MA 01702-5827
(M.L.C, R.W.L, J.M.M., E.S.M., C.S.F., C.J.O.); Department of
Biostatistics, Boston University School of Public Health, Boston, MA
(J.M.M.); Division of Endocrinology, Diabetes and Hypertension, Brigham
and Women's Hospital, Boston, MA (C.S.F.); Cardiac MR, PET and CT
Program, Department of Radiology, Massachusetts General Hospital,
Boston, MA (U.N.); Division of Cardiology, Department of Medicine,
Massachusetts General Hospital, Boston, MA (C.J.O.); Harvard Medical
School, Boston, MA (C.S.F., U.H., C.J.O.). Received April 2, 2013;
accepted August 14, 2013. Source of funding: This project was supported
by the National Heart, Lung, and Blood Institute (NHLBI) Framingham
Heart Study (contract Nos. N01-HC-25195 and N01-HC-38038). Dr O'Donnell
is supported by the NHLBI Division of Intramural Research. There are no
conflicts of interest. Address correspondence to: C.J.O. e-mail:
odonnellc@nhlbi.nih.gov
NR 17
TC 0
Z9 0
U1 1
U2 6
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1076-6332
EI 1878-4046
J9 ACAD RADIOL
JI Acad. Radiol.
PD NOV
PY 2013
VL 20
IS 11
BP 1422
EP 1428
DI 10.1016/j.acra.2013.08.008
PG 7
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 241AW
UT WOS:000326139800013
PM 24119355
ER
PT J
AU Parham, DM
Barr, FG
AF Parham, David M.
Barr, Frederic G.
TI Classification of Rhabdomyosarcoma and Its Molecular Basis
SO ADVANCES IN ANATOMIC PATHOLOGY
LA English
DT Review
DE rhabdomyosarcoma; classification systems; prognosis; genetic testing
ID CHILDRENS ONCOLOGY GROUP; SPINDLE-CELL RHABDOMYOSARCOMA; TISSUE SARCOMA
COMMITTEE; TUMOR ALVEOLAR RHABDOMYOSARCOMA; BECKWITH-WIEDEMANN-SYNDROME;
POLYMERASE-CHAIN-REACTION; INTERGROUP RHABDOMYOSARCOMA; EMBRYONAL
RHABDOMYOSARCOMA; CHILDHOOD RHABDOMYOSARCOMA; FUSION STATUS
AB Rhabdomyosarcoma (RMS), the most common soft tissue sarcoma in children, has traditionally been classified into embryonal rhabdomyosarcoma (ERMS) and alveolar rhabdomyosarcoma (ARMS) for pediatric oncology practice. This review outlines the historical development of classification of childhood RMS and the challenges that have been associated with it, particularly problems with the diagnosis of solid variant ARMS and its distinction from ERMS. In addition to differences in clinical presentation and outcome, a number of genetic features underpin separation of ERMS from ARMS. Genetic differences associated with RMS subclassification include the presence of reciprocal translocations and their associated fusions in ARMS, amplification of genes in ARMS and its fusion subsets, chromosomal losses and gains that mostly occur in ERMS, and allelic losses and mutations usually associated with ERMS. Chimeric proteins encoded in most ARMS from the fusion of PAX3 or PAX7 with FOXO1 are expressed, result in a distinct pattern of downstream protein expression, and appear to be the proximate cause of the bad outcome associated with this subtype. A sizeable minority of ARMS lacks these fusions and shares the clinical and biological features of ERMS. A battery of immunohistochemical tests may prove useful in separating ERMS from ARMS and fusion-positive ARMS from fusion-negative ARMS. Because of limitation of predicting outcome solely based on histologic classification, treatment protocols will begin to utilize fusion testing for stratification of affected patients into low-risk, intermediate-risk, and high-risk groups.
C1 [Parham, David M.] Univ Oklahoma, Hlth Sci Ctr, Dept Pathol, Oklahoma City, OK 73104 USA.
[Barr, Frederic G.] NCI, Lab Pathol, Bethesda, MD 20892 USA.
RP Parham, DM (reprint author), Univ Oklahoma, Hlth Sci Ctr, Dept Pathol, 940 Stanton L Young Blvd,BMSB451, Oklahoma City, OK 73104 USA.
EM david-parham@ouhsc.edu
FU Intramural Program of the National Cancer Institute; Children's Oncology
Group, derived from National Cancer Institute [U10 CA98543]
FX F.G.B. was supported by Intramural Program of the National Cancer
Institute.; D.M.P. receives salary support from the Children's Oncology
Group, derived from National Cancer Institute grant U10 CA98543. The
other author has no conflicts of interest to disclose.
NR 97
TC 36
Z9 39
U1 0
U2 13
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1072-4109
EI 1533-4031
J9 ADV ANAT PATHOL
JI Adv. Anat. Pathol.
PD NOV
PY 2013
VL 20
IS 6
BP 387
EP 397
DI 10.1097/PAP.0b013e3182a92d0d
PG 11
WC Pathology
SC Pathology
GA 242WL
UT WOS:000326275400003
PM 24113309
ER
PT J
AU Hartwell, TD
Pequegnat, W
Moore, JL
Parker, CB
Strader, LC
Green, AM
Quinn, TC
Wasserheit, JN
Klausner, JD
AF Hartwell, Tyler D.
Pequegnat, Willo
Moore, Janet L.
Parker, Corette B.
Strader, Lisa C.
Green, Annette M.
Quinn, Thomas C.
Wasserheit, Judith N.
Klausner, Jeffrey D.
CA NIMH Collaborative HIV STD Prevent
TI The Utility of a Composite Biological Endpoint in HIV/STI Prevention
Trials
SO AIDS AND BEHAVIOR
LA English
DT Article
DE Sexual behavior; Sexually transmitted diseases; HIV/STI prevention;
Simulation of biological outcomes
AB A human immunodeficiency virus (HIV) as a biological endpoint in HIV prevention trials may not be feasible, so investigators have used surrogate biological outcomes. In a multisite trial, the epidemiology of STIs may be different across sites and preclude using one STI as the outcome. This study explored using a composite STI outcome to address that problem. The combined biological endpoint was the incidence of any of six new STIs (chlamydia, gonorrhea, trichomonas (women only), syphilis, herpes simplex virus type 2 infection and HIV) during a 24-month follow up period. We investigated how a composite STI outcome would perform compared to single and dual STI outcomes under various conditions. We simulated outcomes for four populations that represented a wide range of sex and age distributions, and STI prevalences. The simulations demonstrated that a combined biologic outcome was superior to single and dual STI outcomes in assessing intervention effects in 82 % of the cases. A composite biological outcome was effective in detecting intervention effects and might allow more investigations to incorporate multiple biological outcomes in the assessment of behavioral intervention trials for HIV prevention.
C1 [Hartwell, Tyler D.; Moore, Janet L.; Parker, Corette B.; Strader, Lisa C.; Green, Annette M.] Res Triangle Inst, Res Triangle Pk, NC 27709 USA.
[Pequegnat, Willo] NIMH, Bethesda, MD 20892 USA.
[Quinn, Thomas C.] Johns Hopkins Univ, Baltimore, MD USA.
[Wasserheit, Judith N.] Univ Washington, Seattle, WA 98195 USA.
[Klausner, Jeffrey D.] Univ Calif Los Angeles, Los Angeles, CA USA.
RP Pequegnat, W (reprint author), NIMH, 6001 Execut Blvd,Room 6111, Bethesda, MD 20892 USA.
EM wpequegn@mail.nih.gov
FU Intramural NIH HHS [ZIA AI000361-30]; NIMH NIH HHS [U10 MH061536]
NR 14
TC 1
Z9 1
U1 2
U2 5
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 2013
VL 17
IS 9
BP 2893
EP 2901
DI 10.1007/s10461-013-0501-5
PG 9
WC Public, Environmental & Occupational Health; Social Sciences, Biomedical
SC Public, Environmental & Occupational Health; Biomedical Social Sciences
GA 240QW
UT WOS:000326113100005
PM 23748863
ER
PT J
AU Hersch, RK
Cook, RF
Billings, DW
Kaplan, S
Murray, D
Safren, S
Goforth, J
Spencer, J
AF Hersch, Rebekah K.
Cook, Royer F.
Billings, Douglas W.
Kaplan, Seth
Murray, David
Safren, Steven
Goforth, Justin
Spencer, Joy
TI Test of a Web-Based Program to Improve Adherence to HIV Medications
SO AIDS AND BEHAVIOR
LA English
DT Article
DE Medication adherence; Web-based program; ART; Antiretroviral therapy
ID COGNITIVE-BEHAVIORAL THERAPY; RANDOMIZED CONTROLLED-TRIAL;
INJECTION-DRUG-USERS; DEPRESSION CBT-AD; SOCIETY-USA PANEL;
ANTIRETROVIRAL MEDICATIONS; PROTEASE INHIBITORS; INCREASE ADHERENCE;
HEALTH-PROMOTION; INTERVENTION
AB We evaluated the effectiveness of a web-based version of the Life-Steps intervention combined with modules for stress reduction and mood management, designed to improve medication adherence among HIV infected individuals. 168 HIV+ adults were randomized into either the Life-Steps program or a waitlist control condition. All participants completed a baseline assessment and provided a 2-week electronic pill (MEMS) cap baseline reading. Follow up data collection was conducted at 3, 6 and 9 months. Patients in the web-based Life-Steps condition had significantly higher antiretroviral medication adherence rates than patients in the control group over the nine-month period as measured by the MEMS cap. In addition, analysis of viral load data indicated that the program also resulted in a significant decrease in viral load. These findings indicate that a web-based Life-Steps program can be a useful and implementable tool for helping patients living with HIV maintain medication adherence.
C1 [Hersch, Rebekah K.; Cook, Royer F.; Billings, Douglas W.; Spencer, Joy] ISA Associates Inc, Alexandria, VA 22304 USA.
[Kaplan, Seth] George Mason Univ, Dept Psychol, Fairfax, VA 22030 USA.
[Murray, David] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, NIH, Rockville, MD USA.
[Safren, Steven] Harvard Univ, Sch Med, Massachusettes Gen Hosp, Boston, MA USA.
[Goforth, Justin] Whitman Walker Hlth, Washington, DC USA.
RP Hersch, RK (reprint author), ISA Associates Inc, 201 North Union St,Suite 330, Alexandria, VA 22304 USA.
EM rhersch@isagroup.com
FU NIDA NIH HHS [5RC1DA028505, RC1 DA028505]
NR 41
TC 9
Z9 9
U1 3
U2 13
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 2013
VL 17
IS 9
BP 2963
EP 2976
DI 10.1007/s10461-013-0535-8
PG 14
WC Public, Environmental & Occupational Health; Social Sciences, Biomedical
SC Public, Environmental & Occupational Health; Biomedical Social Sciences
GA 240QW
UT WOS:000326113100012
PM 23760634
ER
PT J
AU Pecoraro, A
Royer-Malvestuto, C
Rosenwasser, B
Moore, K
Howell, A
Ma, M
Woody, GE
AF Pecoraro, Anna
Royer-Malvestuto, Charlotte
Rosenwasser, Beth
Moore, Kevin
Howell, Allen
Ma, Michelle
Woody, George E.
TI Factors contributing to dropping out from and returning to HIV treatment
in an inner city primary care HIV clinic in the United States
SO AIDS CARE-PSYCHOLOGICAL AND SOCIO-MEDICAL ASPECTS OF AIDS/HIV
LA English
DT Article
DE HIV; AIDS; attrition; retention; engagement; substance abuse
ID ANTIRETROVIRAL THERAPY; SUBSTANCE-ABUSE; INFECTION; RETENTION; PROGRAMS;
BARRIERS; PATIENT
AB Although advances in pharmacotherapy have enabled people living with HIV/AIDS to live longer, fuller lives, some leave medical care, resulting in sub-optimal treatment and increased health risk to themselves and others. Forty-one patients who dropped out of an urban, publically funded primary care HIV clinic were contacted and encouraged by outreach staff to return. Participants were interviewed within two weeks of returning, and themes associated with dropping out and returning were elicited and content analyzed. Dropping out was associated with drug/alcohol use, unstable housing/homelessness, psychiatric disorders, incarceration, problems with HIV medications, inability to accept the diagnosis, relocation, stigma, problems with the clinic, and forgetfulness. Returning was associated with health concerns, substance abuse treatment/recovery, stable housing, incarceration/release, positive feelings about the clinic, spirituality, and assistance from family/relocation. Because a large number of patients reported substance abuse, depression, and past suicide attempts. Clinic staff should assess substance use, depression, and suicidal ideation at each primary care visit and encourage patients to obtain substance abuse treatment and mental health care. Future interventions could include providing SBIRT and/or onsite mental health and substance abuse treatment, all of which may boost retention.
C1 [Pecoraro, Anna; Royer-Malvestuto, Charlotte; Woody, George E.] Univ Penn, Perelman Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA.
[Pecoraro, Anna; Royer-Malvestuto, Charlotte; Woody, George E.] NIDA Clin Trials Network, Delaware Valley Node, Philadelphia, PA USA.
[Rosenwasser, Beth; Moore, Kevin; Howell, Allen] Philadelphia FIGHT, Philadelphia, PA USA.
[Rosenwasser, Beth] Temple Univ, Dept Educ, Philadelphia, PA 19122 USA.
[Moore, Kevin] AIDS Care Grp, Philadelphia, PA USA.
[Ma, Michelle] Univ Michigan, Sch Med, Philadelphia, PA USA.
[Woody, George E.] Treatment Res Inst, Philadelphia, PA USA.
RP Pecoraro, A (reprint author), Univ Penn, Perelman Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA.
EM annp@mail.med.upenn.edu
FU NIDA NIH HHS [KO5 DA-17009, P60 DA005186, U10 DA-13043]
NR 17
TC 21
Z9 21
U1 1
U2 21
PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD
PI ABINGDON
PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND
SN 0954-0121
EI 1360-0451
J9 AIDS CARE
JI Aids Care-Psychol. Socio-Med. Asp. Aids-Hiv
PD NOV 1
PY 2013
VL 25
IS 11
BP 1399
EP 1406
DI 10.1080/09540121.2013.772273
PG 8
WC Health Policy & Services; Public, Environmental & Occupational Health;
Psychology, Multidisciplinary; Respiratory System; Social Sciences,
Biomedical
SC Health Care Sciences & Services; Public, Environmental & Occupational
Health; Psychology; Respiratory System; Biomedical Social Sciences
GA 244EW
UT WOS:000326370900009
PM 23428205
ER
PT J
AU Marshall, L
Cummins, J
Spiegel, H
Turpin, J
Veronese, F
Kashuba, A
AF Marshall, Leslie
Cummins, James
Spiegel, Hans
Turpin, James
Veronese, Fulvia
Kashuba, Angela
CA HIV Prevention Pharmacology Best P
TI Critical Need for Appropriate Mucosal Sample Collection to Determine
Relational Animal Pharmacokinetic-Pharmacodynamic Models in HIV
Prevention
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Letter
ID HUMANIZED BLT MICE; TRANSMISSION; GENERATION; STRATEGIES; INFECTION
C1 [Marshall, Leslie; Cummins, James; Turpin, James; Veronese, Fulvia] NIAID, Preclin Microbicide & Prevent Res Branch, Prevent Sci Program, DAIDS,NIH, Bethesda, MD 20892 USA.
[Spiegel, Hans] HJF DAIDS, Bethesda, MD USA.
[Kashuba, Angela] Univ N Carolina, Eshelman Sch Pharm, Div Pharmacotherapy & Expt Therapeut, Chapel Hill, NC USA.
[Kashuba, Angela] Univ N Carolina, UNC Ctr AIDS Res, Chapel Hill, NC USA.
RP Marshall, L (reprint author), NIAID, Preclin Microbicide & Prevent Res Branch, Prevent Sci Program, DAIDS,NIH, 6700B Rockledge Dr,Room 5224, Bethesda, MD 20892 USA.
EM marshalllj@niaid.nih.gov
NR 12
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 0889-2229
EI 1931-8405
J9 AIDS RES HUM RETROV
JI Aids Res. Hum. Retrovir.
PD NOV 1
PY 2013
VL 29
IS 11
SI SI
BP 1398
EP 1400
DI 10.1089/aid.2013.1501
PG 3
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 239PI
UT WOS:000326037500499
PM 23909474
ER
PT J
AU Shapiro, SZ
AF Shapiro, Stuart Z.
TI HIV Vaccine Development: Strategies for Preclinical and Clinical
Investigation
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Article
ID HUMANIZED BLT MICE; TRANSMISSION; GENERATION; INFECTION
AB This article discusses HIV vaccine discovery and candidate vaccine testing in the context of current realities of funding and clinical trial practice. Lacking perfect animal models for testing candidate HIV vaccines, clinical investigators have proposed a strategy of iterative exploratory clinical trials in the model of cancer chemotherapy development. Problems with the appropriateness of this model to HIV vaccine development are discussed. Also, the future feasibility of this strategy in the context of increasing clinical trial costs and emerging new, efficacious prevention modalities is questioned. Strategies for making better use of animal models are presented as an alternative to iterative exploratory clinical efficacy testing. Some ways in which better data from preclinical studies can refine clinical product development are described. Finally, development of an HIV vaccine under the FDA's "Animal Rule" pathway to licensure when human efficacy studies are not feasible is discussed as a fall-back approach. Not making a preventive vaccine against HIV infection is simply not an option because eradication of AIDS will require a preventive vaccine.
C1 NIAID, Vaccine Res Program, Div Aids, Bethesda, MD 20892 USA.
RP Shapiro, SZ (reprint author), NIAID, Vaccine Res Program, Div Aids, 6700-B Rockledge Dr,Room 5146, Bethesda, MD 20892 USA.
EM sshapiro@niaid.nih.gov
NR 12
TC 1
Z9 1
U1 1
U2 11
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 2013
VL 29
IS 11
SI SI
BP 1401
EP 1406
DI 10.1089/aid.2013.0142
PG 6
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 239PI
UT WOS:000326037500500
PM 23379343
ER
PT J
AU Malaspina, A
Collins, BS
Dell, A
Alter, G
Onami, TM
AF Malaspina, Angela
Collins, Brenda S.
Dell, Anne
Alter, Galit
Onami, Thandi M.
TI Conference Report: "Functional Glycomics in HIV Type 1 Vaccine Design"
Workshop Report, Bethesda, Maryland, April 30-May 1, 2012
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Article
ID RHESUS MACAQUES; VIRUS; PROTECTION; INFECTION; ANTIBODIES; SIVMAC251;
RESPONSES; NEUTRALIZATION; INOCULATION; SIVSME660
AB A vital part of the renewed hope for a vaccine against the human immunodeficiency virus (HIV-1) is based on recent studies that have highlighted major sites of HIV-1 vulnerability that could be effectively targeted by a preventive vaccine. One of these potential vulnerabilities includes the dense cluster of carbohydrates surrounding HIV-1's envelope glycoproteins gp120 and gp41, typically referred to as the "glycan shield." Recent data from several laboratories have shown that glycans on the HIV-1 envelope form key epitopes for broadly neutralizing antibodies (bNAb). Moreover, HIV-1 envelope glycans play an important role in viral transmission, antigenicity, and immunogenicity. The recent availability of novel tools and technologies has now allowed investigators to leverage glycomic structure-function relationships in the design of candidate HIV-1 vaccines. Additionally, glycans modulate the immune response, playing an essential role in Fc receptor and complement activity. To promote cross-disciplinary collaboration and promote synergistic HIV-1- glycomics research, the National Institutes of Health (NIH) co-sponsored and convened a 1.5-day workshop entitled "Functional Glycomics in HIV-1 Vaccine Design." The meeting focused on the role of glycan interactions with neutralizing antibodies, the influence of immunoglobulin G (IgG) Fc receptor glycosylation, newly available glycomics technologies, and how new information on the role of glycans could be applied in HIV-1 immunogen design strategies. This report summarizes the discussions of this workshop.
C1 [Malaspina, Angela] US Natl Inst Allergy & Infect Dis, Preclin Res & Dev Branch, Div Aids, Bethesda, MD USA.
[Collins, Brenda S.] HJF DAIDS, Bethesda, MD USA.
[Dell, Anne] Univ London Imperial Coll Sci Technol & Med, Div Mol Biosci, London, England.
[Alter, Galit] Ragon Inst Massachusetts Gen Hosp,Massachusetts I, Charlestown, MA USA.
[Onami, Thandi M.] US Natl Inst Allergy & Infect Dis, Vaccine Clin Res Branch, Div Aids, Bethesda, MD USA.
RP Malaspina, A (reprint author), NIAID, DAIDS, VRP Preclin Res & Dev Branch, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM amalaspina@niaid.nih.gov; thandi.onami@nih.gov
FU National Institute of Allergy and Infectious Diseases, National
Institutes of Health, Department of Health and Human Services
[HHSN272200800014C]
FX The authors would like to thank all the speakers for their presentations
and all the attendees for their participation in the discussions. This
project has been funded in whole or in part with federal funds from the
National Institute of Allergy and Infectious Diseases, National
Institutes of Health, Department of Health and Human Services, under
contract no. HHSN272200800014C.
NR 23
TC 0
Z9 1
U1 1
U2 12
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 2013
VL 29
IS 11
SI SI
BP 1407
EP 1417
DI 10.1089/aid.2013.0102
PG 11
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 239PI
UT WOS:000326037500501
PM 23767872
ER
PT J
AU Romano, J
Kashuba, A
Becker, S
Cummins, J
Turpin, J
Veronese, F
AF Romano, Joseph
Kashuba, Angela
Becker, Stephen
Cummins, James
Turpin, Jim
Veronese, Fulvia
CA Antiretroviral Pharmacology HIV
TI Pharmacokinetics and Pharmacodynamics in HIV Prevention; Current Status
and Future Directions: A Summary of the DAIDS and BMGF Sponsored Think
Tank on Pharmacokinetics (PK)/Pharmacodynamics (PD) in HIV Prevention
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; DEPENDENT CELLULAR CYTOTOXICITY;
MONOCLONAL-ANTIBODY 2G12; N-LINKED GLYCAN; POTENT NEUTRALIZATION;
ANTIGEN PRESENTATION; IMMUNE-RESPONSES; CONFORMATIONAL EPITOPE; BROAD
NEUTRALIZATION; ANTIVIRAL ACTIVITY
AB Thirty years after its beginning, the HIV/AIDS epidemic is still raging around the world. According to UNAIDS, in 2011 alone 1.7M deaths were attributable to AIDS, and 2.5M people were newly infected by the virus. Despite the success in treating HIV-infected people with potent antiretroviral drugs, preventing HIV infection is the key to ending the epidemic. Recently, the efficacy of topical and systemic antiviral chemoprophylaxis (i.e., pre-exposure prophylaxis or "PrEP"), using the same drugs used for HIV treatment, has been demonstrated in a number of clinical trials. However, results from other trials have been inconsistent, especially those evaluating PrEP in women. These inconsistencies may result from our incomplete understanding of pharmacokinetics (PK)/pharmacodynamics (PD) at the mucosal sites of sexual transmission: the male and female gastrointestinal and reproductive tracts. The drug concentrations used in these trials were derived from those used for treatment; however, we still do not know the relationship between the therapeutic and the preventive dose. This article presents the first comprehensive review of the available data in the HIV pharmacology field from animal models to human studies, and outlines gaps, challenges, and future directions. Addressing these pharmacological gaps and challenges will be critical in selecting and advancing future PrEP candidates and strategies with the greatest impact on the HIV epidemic.
C1 [Romano, Joseph] NWJ Grp LLC, Wayne, PA USA.
[Kashuba, Angela] Univ N Carolina, Chapel Hill, NC USA.
[Becker, Stephen] BMGF, Seattle, WA USA.
[Cummins, James; Turpin, Jim; Veronese, Fulvia] NIAID, PSP, DAIDS, NIH, Bethesda, MD 20892 USA.
RP Veronese, F (reprint author), NIAID, PSP, DAIDS, NIH, 5th Floor,Room 5122 6700B Rockledge Dr, Bethesda, MD 20892 USA.
EM fv10x@nih.gov
FU NIAID/DAIDS CRMP [HHSN272201000001C]
FX The Think Tank was funded via the NIAID/DAIDS CRMP contract
(HHSN272201000001C). J.R. wrote the first draft of the manuscript and
A.K. and F.V. coordinated the revised versions. All authors (including
S.B., J.C., and J.T.) and Think Tank participants contributed to the
final version of the manuscript and approved it.
NR 82
TC 18
Z9 18
U1 2
U2 14
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 2013
VL 29
IS 11
SI SI
BP 1418
EP 1427
DI 10.1089/aid.2013.0122
PG 10
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 239PI
UT WOS:000326037500502
PM 23614610
ER
PT J
AU Ling, BH
Rogers, L
Johnson, AM
Piatak, M
Lifson, J
Veazey, RS
AF Ling, Binhua
Rogers, Linda
Johnson, Ann-Marie
Piatak, Michael
Lifson, Jeffrey
Veazey, Ronald S.
TI Effect of Combination Antiretroviral Therapy on Chinese Rhesus Macaques
of Simian Immunodeficiency Virus Infection
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Article
ID TYPE-1 ENTRY INHIBITORS; HUMAN SERUM-ALBUMIN; HIV ENTRY; ENVELOPE
GLYCOPROTEIN; MONOCLONAL-ANTIBODY; SEXUAL TRANSMISSION; CORE STRUCTURE;
GP41; FUSION; MICROBICIDES
AB Definitive treatment of HIV infection remains a critical but elusive goal, with persistence of residual virus even in the face of prolonged administration of suppressive combination antiretroviral treatment (cART) providing a source for recrudescent infection if treatment is stopped. Characterization of the residual virus and devising strategies to target it for eradication are key goals in HIV treatment research. Indian rhesus macaques (In-RM) infected with SIVmac have been widely used in such research. However, it has proven challenging to achieve and sustain clinically relevant levels of suppression (< 30 vRNA copies/ml plasma) with cART in such models. As ease of viral suppression by cART is related to pretreatment levels of viral replication, and levels of replication of SIVmac239/251 are lower in Chinese rhesus macaques (Ch-RM) than in In-RM, we evaluated cART administration to SIVmac-infected Ch-RM as a potential model for studies of residual virus and eradication strategies. Four SIVmac239-infected Ch-RM received cART including reverse transcriptase inhibitors PMPA/FTC and integrase inhibitor L-870812 daily for 8 weeks. Plasma viral loads were promptly reduced to < 30 copies/ml upon initiation of cART. Cell-associated SIV DNA levels in lymphocytes from the gut were also significantly reduced. Jejunal and colonic CCR5(+)CD4(+) mucosal memory T cells increased significantly; restoration of these cells was associated with reductions in immune activation. In conclusion, cART effectively suppressed viral replication to < 30 vRNA copies/ml in SIVmac239-infected Ch-RM, reducing immune activation and restoring mucosal immune cell populations. SIVmac239-infected Ch-RM may be a useful model for studying responses to cART and persistent tissue reservoirs and evaluating candidate eradication strategies to cure HIV infection.
C1 [Ling, Binhua; Rogers, Linda; Johnson, Ann-Marie; Veazey, Ronald S.] Tulane Natl Primate Res Ctr, Covington, LA 70433 USA.
[Ling, Binhua] Tulane Univ, Sch Med, Dept Microbiol & Immunol, New Orleans, LA 70112 USA.
[Piatak, Michael; Lifson, Jeffrey] NCI, AIDS & Canc Virus Program, SAIC Frederick Inc, Frederick, MD 21701 USA.
[Veazey, Ronald S.] Tulane Univ, Sch Med, Dept Pathol, New Orleans, LA 70112 USA.
RP Ling, BH (reprint author), Tulane Natl Primate Res Ctr, Div Comparat Pathol, 18703 3 Rivers Rd, Covington, LA 70433 USA.
EM bling@tulane.edu
FU NIAID [R01 AI093307-01A1]; Tulane Research Enhancement grant; National
Center for Research Resources; Office of Research Infrastructure
Programs (ORIP) of the National Institutes of Health [OD011104-51]; NCI/
NIH [HHSN261200800001E]; [R01 AI084793]
FX We thank C. Lanclos and J. Bruhn of the immunology flow cytometry core
laboratory, M. Duplantis and L. Li for tissue sample collection, and L.
Doyle-Meyers and the animal care staff of the Department of Veterinary
Medicine for their technical assistance. Research was supported by NIAID
R01 AI093307-01A1 (BL), R01 AI084793 (RSV), a Tulane Research
Enhancement grant (BL), and the National Center for Research Resources,
and the Office of Research Infrastructure Programs (ORIP) of the
National Institutes of Health through grant OD011104-51 and in part with
federal funds from NCI/ NIH contract HHSN261200800001E. The funders had
no role in the study design, data collection and analysis, decision to
publish, or preparation of the article.
NR 30
TC 6
Z9 6
U1 0
U2 3
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 2013
VL 29
IS 11
SI SI
BP 1465
EP 1474
DI 10.1089/aid.2012.0378
PG 10
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 239PI
UT WOS:000326037500508
PM 23387294
ER
PT J
AU Adamson, B
Wakefield, S
Flood, D
Stoff, D
Sopher, C
Cook, R
Pemberton, N
Kublin, J
Fuchs, J
AF Adamson, B.
Wakefield, S.
Flood, D.
Stoff, D.
Sopher, C.
Cook, R.
Pemberton, N.
Kublin, J.
Fuchs, J.
CA NIAID HIV Vaccine Trials Network
TI HVTN Mentored Research Program for Black and Latino/a Medical Students
Increases Intent to Pursue a Career in HIV/AIDS Vaccine Research
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT Conference on AIDS Vaccine
CY OCT 07-10, 2013
CL Barcelona, SPAIN
C1 [Adamson, B.; Wakefield, S.; Flood, D.; Sopher, C.; Cook, R.; Pemberton, N.; Kublin, J.; NIAID HIV Vaccine Trials Network] HIV Vaccine Trials Network, Seattle, WA USA.
[Stoff, D.] NIMH, Bethesda, MD 20892 USA.
[Fuchs, J.] San Francisco Dept Publ Hlth, San Francisco, CA USA.
NR 0
TC 0
Z9 0
U1 0
U2 6
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 2013
VL 29
IS 11
SI SI
BP A65
EP A65
PG 1
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 239PI
UT WOS:000326037500163
ER
PT J
AU Bhiman, JN
Doria-Rose, N
Moore, PL
Nonyane, M
Karim, SSA
Kwong, PD
Mascola, JR
Morris, L
AF Bhiman, J. N.
Doria-Rose, N.
Moore, P. L.
Nonyane, M.
Karim, S. S. Abdool
Kwong, P. D.
Mascola, J. R.
Morris, L.
TI Interplay Between Broadly Cross-Neutralizing V2 Monoclonal Antibodies
and Autologous Viral Evolution
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT Conference on AIDS Vaccine
CY OCT 07-10, 2013
CL Barcelona, SPAIN
C1 [Bhiman, J. N.; Moore, P. L.; Nonyane, M.; Morris, L.] Natl Hlth Lab Serv, Natl Inst Communicable Dis, Johannesburg, South Africa.
[Bhiman, J. N.; Moore, P. L.; Morris, L.] Univ Witwatersrand, Johannesburg, South Africa.
[Doria-Rose, N.; Kwong, P. D.; Mascola, J. R.] NIAID, NIH, Bethesda, MD 20892 USA.
[Karim, S. S. Abdool] Univ KwaZulu Natal, CAPRISA, Durban, South Africa.
NR 0
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 2013
VL 29
IS 11
SI SI
BP A12
EP A12
PG 1
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 239PI
UT WOS:000326037500024
ER
PT J
AU Bonsignori, M
Wiehe, K
Lynch, RM
Grimm, SK
Kozink, DM
Hwang, K
Eudailey, JA
Yang, G
Ackerman, ME
Kelsoe, G
Liao, H
Moody, MA
Kepler, TB
Montefiori, DC
Mascola, JR
Haynes, BF
AF Bonsignori, M.
Wiehe, K.
Lynch, R. M.
Grimm, S. K.
Kozink, D. M.
Hwang, K.
Eudailey, J. A.
Yang, G.
Ackerman, M. E.
Kelsoe, G.
Liao, H.
Moody, M. A.
Kepler, T. B.
Montefiori, D. C.
Mascola, J. R.
Haynes, B. F.
TI Isolation and Characterization of an Autoreactive CD4bs Broad
Neutralizing Antibody from a Chronic HIV-1 Controller with Systemic
Lupus Erythematosus
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT Conference on AIDS Vaccine
CY OCT 07-10, 2013
CL Barcelona, SPAIN
C1 [Bonsignori, M.; Wiehe, K.; Kozink, D. M.; Hwang, K.; Eudailey, J. A.; Yang, G.; Kelsoe, G.; Liao, H.; Moody, M. A.; Montefiori, D. C.; Haynes, B. F.] Duke Univ, Med Ctr, Durham, NC USA.
[Lynch, R. M.; Mascola, J. R.] NIH, Bethesda, MD 20892 USA.
[Grimm, S. K.; Ackerman, M. E.] Dartmouth Coll, Hanover, NH 03755 USA.
[Kepler, T. B.] Boston Univ, Sch Med, Boston, MA 02118 USA.
NR 0
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 0889-2229
EI 1931-8405
J9 AIDS RES HUM RETROV
JI Aids Res. Hum. Retrovir.
PD NOV 1
PY 2013
VL 29
IS 11
SI SI
BP A45
EP A46
PG 2
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 239PI
UT WOS:000326037500109
ER
PT J
AU Caskey, M
Trumpfheller, C
Schlesinger, S
Pollak, S
Sinnenberg, L
Pring, J
Hurley, A
Shimeliovich, I
Sarma, P
Yipp, B
Mehandru, S
Anandasabapathy, N
Steinman, R
Keler, T
Koup, R
Bailer, R
Tomaras, G
Sato, A
AF Caskey, M.
Trumpfheller, C.
Schlesinger, S.
Pollak, S.
Sinnenberg, L.
Pring, J.
Hurley, A.
Shimeliovich, I.
Sarma, P.
Yipp, B.
Mehandru, S.
Anandasabapathy, N.
Steinman, R.
Keler, T.
Koup, R.
Bailer, R.
Tomaras, G.
Sato, A.
TI In Vivo Targeting of HIV Gag to Dendritic Cells Given with Poly ICLC Is
Safe and Induces Durable CD4 T Cell and B Cell Responses in Healthy
Volunteers
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT Conference on AIDS Vaccine
CY OCT 07-10, 2013
CL Barcelona, SPAIN
C1 [Caskey, M.; Trumpfheller, C.; Schlesinger, S.; Pollak, S.; Sinnenberg, L.; Pring, J.; Hurley, A.; Shimeliovich, I.; Sarma, P.; Yipp, B.; Mehandru, S.; Anandasabapathy, N.; Steinman, R.] Rockefeller Univ, New York, NY 10021 USA.
[Keler, T.] Celldex Therapeut, Phillipsburg, NJ USA.
[Koup, R.] NIH, Bethesda, MD 20892 USA.
[Bailer, R.] NIAID, Vaccine Immune T Cell & Antibody Lab, Bethesda, MD 20892 USA.
[Tomaras, G.] Duke Univ, Durham, NC USA.
[Sato, A.] Stat Ctr HIV AIDS Res, Seattle, WA USA.
RI Tomaras, Georgia/J-5041-2016
NR 0
TC 0
Z9 0
U1 0
U2 3
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 2013
VL 29
IS 11
SI SI
BP A65
EP A65
PG 1
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 239PI
UT WOS:000326037500162
ER
PT J
AU Chuang, G
Zhang, B
Lloyd, K
Eudailey, J
Blinn, J
McKee, K
Kwon, Y
Mascola, JR
Haynes, BF
Georgiev, IS
Kwong, PD
AF Chuang, G.
Zhang, B.
Lloyd, K.
Eudailey, J.
Blinn, J.
McKee, K.
Kwon, Y.
Mascola, J. R.
Haynes, B. F.
Georgiev, I. S.
Kwong, P. D.
TI Eliminating Autoreactivity of Variants of Antibody VRC07 by Glycan
Masking
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT Conference on AIDS Vaccine
CY OCT 07-10, 2013
CL Barcelona, SPAIN
C1 [Chuang, G.; Zhang, B.; McKee, K.; Kwon, Y.; Mascola, J. R.; Georgiev, I. S.; Kwong, P. D.] NIAID, NIH, Bethesda, MD 20892 USA.
[Lloyd, K.; Eudailey, J.; Blinn, J.; Haynes, B. F.] Duke Univ, Med Ctr, Durham, NC USA.
RI Kwon, Young Do/A-6957-2010
NR 0
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 0889-2229
EI 1931-8405
J9 AIDS RES HUM RETROV
JI Aids Res. Hum. Retrovir.
PD NOV 1
PY 2013
VL 29
IS 11
SI SI
BP A55
EP A55
PG 1
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 239PI
UT WOS:000326037500135
ER
PT J
AU Cicala, C
AF Cicala, C.
TI Inhibition of B Cell Function by HIV-1 Envelope: Role of Binding to
Integrin alpha 4 beta 7
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT Conference on AIDS Vaccine
CY OCT 07-10, 2013
CL Barcelona, SPAIN
C1 [Cicala, C.] NIAID, NIH, Bethesda, MD 20892 USA.
NR 0
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 2013
VL 29
IS 11
SI SI
BP A56
EP A56
PG 1
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 239PI
UT WOS:000326037500138
ER
PT J
AU Connors, M
Rogan, DC
Kelly, EP
Toulmin, SA
Zimmerman, MG
Migueles, SA
AF Connors, M.
Rogan, D. C.
Kelly, E. P.
Toulmin, S. A.
Zimmerman, M. G.
Migueles, S. A.
TI Cytotoxic Capacity During a Recall Response Parallels Increases in Lytic
Granule Contents of Virus-Specific CD8+T Cells
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT Conference on AIDS Vaccine
CY OCT 07-10, 2013
CL Barcelona, SPAIN
C1 [Connors, M.; Rogan, D. C.; Kelly, E. P.; Toulmin, S. A.; Zimmerman, M. G.; Migueles, S. A.] NIAID, NIH, Bethesda, MD 20892 USA.
NR 0
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 2013
VL 29
IS 11
SI SI
BP A135
EP A135
PG 1
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 239PI
UT WOS:000326037500352
ER
PT J
AU De Rosa, SC
Frahm, N
Diaz, G
Newling, P
Morris, D
Morgan, C
Graham, B
Swann, E
Maenza, J
Duerr, A
McElrath, MJ
AF De Rosa, S. C.
Frahm, N.
Diaz, G.
Newling, P.
Morris, D.
Morgan, C.
Graham, B.
Swann, E.
Maenza, J.
Duerr, A.
McElrath, M. J.
TI No Increase in Activated T Cells and Limited Increase in
Adenovirus-Specific T Cells in Colon and Rectal Mucosa Following HIV-1
DNA/rAd5 Immunization
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT Conference on AIDS Vaccine
CY OCT 07-10, 2013
CL Barcelona, SPAIN
C1 [De Rosa, S. C.; Frahm, N.; Diaz, G.; Newling, P.; Morris, D.; Morgan, C.; Maenza, J.; Duerr, A.; McElrath, M. J.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Graham, B.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Swann, E.] NIAID, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
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 2013
VL 29
IS 11
SI SI
BP A180
EP A181
PG 2
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 239PI
UT WOS:000326037500472
ER
PT J
AU Deschamps, M
Morgan, C
Zorrilla, C
Metch, B
Donastorg, Y
Joseph, P
Swann, E
Madenwald, T
Escamilla, G
Pape, JW
AF Deschamps, M.
Morgan, C.
Zorrilla, C.
Metch, B.
Donastorg, Y.
Joseph, P.
Swann, E.
Madenwald, T.
Escamilla, G.
Pape, J. W.
CA H Protocol Team
TI Feasibility of Enrolling Female Commercial Sex Workers at High Risk of
HIV Infection for HIV Vaccine Trials in the Caribbean
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT Conference on AIDS Vaccine
CY OCT 07-10, 2013
CL Barcelona, SPAIN
C1 [Deschamps, M.; Joseph, P.; Pape, J. W.] GHESKIO, Port Au Prince, Haiti.
[Morgan, C.; Metch, B.; Madenwald, T.; Escamilla, G.; H Protocol Team] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Zorrilla, C.] Univ Puerto Rico, Sch Med, Maternal & Infant Studies Ctr CEMI, San Juan, PR 00936 USA.
[Donastorg, Y.] Unidad Vacunas IDCP COIN DIGECITSS, Santo Domingo, Dominican Rep.
[Swann, E.] NIAID, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 3
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 2013
VL 29
IS 11
SI SI
BP A64
EP A64
PG 1
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 239PI
UT WOS:000326037500159
ER
PT J
AU Doria-Rose, NA
Moore, P
Staupe, R
Bhiman, J
Ernandes, M
Georgiev, I
Bailer, R
Louder, M
O'Dell, S
Mckee, K
Crooks, E
Schmidt, S
Karim, SA
Gorman, J
Schramm, C
Longo, N
Pancera, M
Rudicell, R
Yang, Y
Zhang, Z
Zhu, J
Binley, J
Shapiro, L
Kwong, P
Morris, L
Mascola, J
AF Doria-Rose, N. A.
Moore, P.
Staupe, R.
Bhiman, J.
Ernandes, M.
Georgiev, I.
Bailer, R.
Louder, M.
O'Dell, S.
Mckee, K.
Crooks, E.
Schmidt, S.
Karim, S. Abdool
Gorman, J.
Schramm, C.
Longo, N.
Pancera, M.
Rudicell, R.
Yang, Y.
Zhang, Z.
Zhu, J.
Binley, J.
Shapiro, L.
Kwong, P.
Morris, L.
Mascola, J.
TI A Family of Broad and Highly Potent V1V2-Directed HIV-1 Neutralizing
Antibodies with Long CDRH3s from a South African Seroconverter
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT Conference on AIDS Vaccine
CY OCT 07-10, 2013
CL Barcelona, SPAIN
C1 [Doria-Rose, N. A.; Staupe, R.; Ernandes, M.; Georgiev, I.; Bailer, R.; Louder, M.; O'Dell, S.; Mckee, K.; Schmidt, S.; Gorman, J.; Longo, N.; Pancera, M.; Rudicell, R.; Yang, Y.; Zhu, J.; Kwong, P.; Mascola, J.] NIH, Bethesda, MD 20892 USA.
[Moore, P.; Bhiman, J.; Morris, L.] Natl Inst Communicable Dis, Natl Hlth Lab Serv, Johannesburg, South Africa.
[Crooks, E.; Binley, J.] Torrey Pines Inst, San Diego, CA USA.
[Karim, S. Abdool] Univ KwaZulu Natal, CAPRISA, Durban, South Africa.
[Schramm, C.; Zhang, Z.; Shapiro, L.] Columbia Univ, New York, NY USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
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 2013
VL 29
IS 11
SI SI
BP A48
EP A48
PG 1
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 239PI
UT WOS:000326037500115
ER
PT J
AU Enama, ME
Novik, L
Hendel, CS
Holman, L
Plummer, S
Gordon, I
Vasilenko, O
Graham, BS
Ledgerwood, JE
AF Enama, M. E.
Novik, L.
Hendel, C. S.
Holman, L.
Plummer, S.
Gordon, I.
Vasilenko, O.
Graham, B. S.
Ledgerwood, J. E.
TI Eligibility Assessments of Healthy Adults for Eleven HIV Vaccine
Clinical Trials Conducted Through a Screening Protocol: 2002-2013
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT Conference on AIDS Vaccine
CY OCT 07-10, 2013
CL Barcelona, SPAIN
C1 [Enama, M. E.; Novik, L.; Hendel, C. S.; Holman, L.; Plummer, S.; Gordon, I.; Vasilenko, O.; Graham, B. S.; Ledgerwood, J. E.] NIAID, VRC, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
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 2013
VL 29
IS 11
SI SI
BP A72
EP A73
PG 2
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 239PI
UT WOS:000326037500181
ER
PT J
AU Felber, BK
Kulkarni, V
Valentin, A
Rosati, M
Alicea, C
Sardesai, NY
Le Gall, S
Mothe, B
Brander, C
Rolland, M
Mullins, JI
Pavlakis, GN
AF Felber, B. K.
Kulkarni, V.
Valentin, A.
Rosati, M.
Alicea, C.
Sardesai, N. Y.
Le Gall, S.
Mothe, B.
Brander, C.
Rolland, M.
Mullins, J. I.
Pavlakis, G. N.
TI Altered Immunodominance Hierarchy and Increased T-Cell Breadth upon
HIV-1 Conserved Element DNA Vaccination in Macaques
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT Conference on AIDS Vaccine
CY OCT 07-10, 2013
CL Barcelona, SPAIN
C1 [Felber, B. K.; Kulkarni, V.; Valentin, A.; Rosati, M.; Alicea, C.; Pavlakis, G. N.] NCI, Frederick, MD 21701 USA.
[Sardesai, N. Y.] Inovio Pharmaceut Inc, Blue Bell, PA USA.
[Le Gall, S.] MIT & Harvard, Ragon Inst MGH, Cambridge, MA USA.
[Mothe, B.; Brander, C.] Autonomous Univ Barcelona, IrsiCaixa AIDS Res Inst HIVACAT, Barcelona, Spain.
[Rolland, M.; Mullins, J. I.] Univ Washington, Seattle, WA 98195 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
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 2013
VL 29
IS 11
SI SI
BP A33
EP A33
PG 1
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 239PI
UT WOS:000326037500075
ER
PT J
AU Francica, J
Zhanhai, Z
Schmidt, S
Mascola, J
Singh, M
O'Hagan, D
Martin, M
Shapiro, L
Seder, R
AF Francica, J.
Zhanhai, Z.
Schmidt, S.
Mascola, J.
Singh, M.
O'Hagan, D.
Martin, M.
Shapiro, L.
Seder, R.
TI Genetic Assessment of B Cell Responses Following Immunization with HIV
Env Protein and Adjuvants or Pathogenic SHIV Infection in Non-human
Primates
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT Conference on AIDS Vaccine
CY OCT 07-10, 2013
CL Barcelona, SPAIN
C1 [Francica, J.; Schmidt, S.; Mascola, J.; Seder, R.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Zhanhai, Z.; Shapiro, L.] Columbia Univ, New York, NY USA.
[Singh, M.; O'Hagan, D.] Novartis Vaccines & Diagnost, Cambridge, MA USA.
[Martin, M.] NIAID, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 2
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 2013
VL 29
IS 11
SI SI
BP A166
EP A167
PG 2
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 239PI
UT WOS:000326037500436
ER
PT J
AU Frank, I
Grunenberg, N
Hural, J
Edlesfsen, P
DeCamp, A
Allen, M
Spearman, P
Bar, K
Kalams, S
Baden, L
Keefer, M
Fuchs, J
Novak, R
Graham, B
Enama, M
Frahm, N
AF Frank, I.
Grunenberg, N.
Hural, J.
Edlesfsen, P.
DeCamp, A.
Allen, M.
Spearman, P.
Bar, K.
Kalams, S.
Baden, L.
Keefer, M.
Fuchs, J.
Novak, R.
Graham, B.
Enama, M.
Frahm, N.
TI Enhanced HIV-Specific CD8+T Cell Responses Following Polytopic
Administration of VRC rAd5 gag-pol/env A/B/C in HIV-Uninfected Healthy
Adults
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT Conference on AIDS Vaccine
CY OCT 07-10, 2013
CL Barcelona, SPAIN
C1 [Frank, I.; Bar, K.] Univ Penn, Philadelphia, PA 19104 USA.
[Grunenberg, N.; Hural, J.; Edlesfsen, P.; DeCamp, A.; Frahm, N.] Univ Washington, Seattle, WA 98195 USA.
[Allen, M.] NIAID, Div Aids, Bethesda, MD 20892 USA.
[Spearman, P.] Emory Univ, Atlanta, GA 30322 USA.
[Kalams, S.] Vanderbilt Univ, Nashville, TN 37235 USA.
[Baden, L.] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Keefer, M.] Univ Rochester, Rochester, NY USA.
[Fuchs, J.] San Francisco Dept Publ Hlth, San Francisco, CA USA.
[Novak, R.] Univ Illinois, Chicago, IL USA.
[Graham, B.; Enama, M.] Vaccine Res Ctr, Bethesda, MD USA.
NR 0
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 0889-2229
EI 1931-8405
J9 AIDS RES HUM RETROV
JI Aids Res. Hum. Retrovir.
PD NOV 1
PY 2013
VL 29
IS 11
SI SI
BP A63
EP A63
PG 1
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 239PI
UT WOS:000326037500157
ER
PT J
AU Fuchs, JD
Frank, I
Elizaga, M
Kochar, N
Allen, M
Frahm, N
Carter, DK
Li, S
Edupuganti, S
Kalams, S
Sheets, R
Pensiero, M
Latham, T
Egan, M
Clarke, D
Eldridge, J
AF Fuchs, J. D.
Frank, I.
Elizaga, M.
Kochar, N.
Allen, M.
Frahm, N.
Carter, D. K.
Li, S.
Edupuganti, S.
Kalams, S.
Sheets, R.
Pensiero, M.
Latham, T.
Egan, M.
Clarke, D.
Eldridge, J.
TI A Recombinant Vesicular Stomatitis Virus (rVSV) HIV-1 Gag Vaccine Is
Safe and Immunogenic in Healthy, HIV-1 Uninfected Phase I Trial
Participants
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT Conference on AIDS Vaccine
CY OCT 07-10, 2013
CL Barcelona, SPAIN
C1 [Fuchs, J. D.] San Francisco Dept Publ Hlth, San Francisco, WA USA.
[Frank, I.] Univ Penn, Philadelphia, PA 19104 USA.
[Elizaga, M.; Kochar, N.; Frahm, N.; Carter, D. K.; Li, S.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Allen, M.; Sheets, R.; Pensiero, M.] NIAID, Bethesda, MD 20892 USA.
[Edupuganti, S.] Emory Univ, Atlanta, GA 30322 USA.
[Kalams, S.] Vanderbilt Univ, Nashville, TN 37235 USA.
[Latham, T.; Egan, M.; Clarke, D.; Eldridge, J.] Profectus BioSci Inc, Tarrytown, NY USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
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 2013
VL 29
IS 11
SI SI
BP A74
EP A75
PG 2
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 239PI
UT WOS:000326037500186
ER
PT J
AU Gao, F
Bonsignori, M
Liao, H
Kumar, A
Xia, S
Cai, F
Lu, X
Kozink, DM
Kwong, P
Zhou, T
Lynch, R
Alam, SM
Ferrari, G
Kelsoe, G
Sandrasegaram, G
Shaw, GM
Hahn, BH
Montefiori, DC
Kamanga, G
Cohen, M
Braber, P
Korber, BT
Mascola, JR
Kepler, TB
Haynes, BF
AF Gao, F.
Bonsignori, M.
Liao, H.
Kumar, A.
Xia, S.
Cai, F.
Lu, X.
Kozink, D. M.
Kwong, P.
Zhou, T.
Lynch, R.
Alam, S. M.
Ferrari, G.
Kelsoe, G.
Sandrasegaram, G.
Shaw, G. M.
Hahn, B. H.
Montefiori, D. C.
Kamanga, G.
Cohen, M.
Braber, P.
Korber, B. T.
Mascola, J. R.
Kepler, T. B.
Haynes, B. F.
TI Multiple Pathways of HIV-1 Autologous Neutralizing Antibodies Cooperate
to Drive CD4 Binding Site Broadly Neutralizing Antibody Responses
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT Conference on AIDS Vaccine
CY OCT 07-10, 2013
CL Barcelona, SPAIN
C1 [Gao, F.; Bonsignori, M.; Liao, H.; Kumar, A.; Xia, S.; Cai, F.; Lu, X.; Kozink, D. M.; Alam, S. M.; Ferrari, G.; Kelsoe, G.; Montefiori, D. C.; Haynes, B. F.] Duke Univ, Med Ctr, Durham, NC USA.
[Kwong, P.; Zhou, T.; Lynch, R.; Mascola, J. R.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Sandrasegaram, G.; Braber, P.; Korber, B. T.] Los Alamos Natl Lab, Los Alamos, NM USA.
[Shaw, G. M.; Hahn, B. H.] Univ Penn, Philadelphia, PA 19104 USA.
[Kamanga, G.; Cohen, M.] Univ N Carolina, Chapel Hill, NC USA.
[Kepler, T. B.] Boston Univ, Boston, MA 02215 USA.
RI Zhou, Tongqing/A-6880-2010
OI Zhou, Tongqing/0000-0002-3935-4637
NR 0
TC 0
Z9 0
U1 0
U2 2
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 2013
VL 29
IS 11
SI SI
BP A186
EP A186
PG 1
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 239PI
UT WOS:000326037500485
ER
PT J
AU Georgiev, IS
Rudicell, RS
Saunders, KO
Shi, W
Kirys, T
Mckee, K
O'Dell, S
Chuang, G
Yang, Z
Ofek, G
Mascola, JR
Nabel, GJ
Kwong, PD
AF Georgiev, I. S.
Rudicell, R. S.
Saunders, K. O.
Shi, W.
Kirys, T.
Mckee, K.
O'Dell, S.
Chuang, G.
Yang, Z.
Ofek, G.
Mascola, J. R.
Nabel, G. J.
Kwong, P. D.
TI Antibodies VRC01 and 10E8 Require Minimal Somatic Framework Mutations to
Achieve High Neutralization Breadth and Potency
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT Conference on AIDS Vaccine
CY OCT 07-10, 2013
CL Barcelona, SPAIN
C1 [Georgiev, I. S.; Rudicell, R. S.; Saunders, K. O.; Shi, W.; Kirys, T.; Mckee, K.; O'Dell, S.; Chuang, G.; Yang, Z.; Ofek, G.; Mascola, J. R.; Nabel, G. J.; Kwong, P. D.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
NR 0
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 0889-2229
EI 1931-8405
J9 AIDS RES HUM RETROV
JI Aids Res. Hum. Retrovir.
PD NOV 1
PY 2013
VL 29
IS 11
SI SI
BP A164
EP A165
PG 2
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 239PI
UT WOS:000326037500430
ER
PT J
AU Gonzalez, N
Lynch, RM
McKee, K
Yuste, E
Mascola, JR
Alcami, J
AF Gonzalez, N.
Lynch, R. M.
McKee, K.
Yuste, E.
Mascola, J. R.
Alcami, J.
TI Characterization of Broadly Neutralizing Antibodies (bNAbs) to HIV-1
Present in a Cohort of Long Term Non-Progressors (LTNPs)
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT Conference on AIDS Vaccine
CY OCT 07-10, 2013
CL Barcelona, SPAIN
C1 [Gonzalez, N.; Alcami, J.] Inst Salud Carlos III, Ctr Nacl Microbiol, Madrid, Spain.
[Lynch, R. M.; McKee, K.; Mascola, J. R.] NIH, Bethesda, MD 20892 USA.
[Yuste, E.] Hosp Clin Barcelona, Barcelona, Spain.
NR 0
TC 0
Z9 0
U1 0
U2 6
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 2013
VL 29
IS 11
SI SI
BP A53
EP A53
PG 1
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 239PI
UT WOS:000326037500130
ER
PT J
AU Gordon, SN
Vaccari, M
Doster, MN
Liyanage, NP
Pegu, P
Schifanella, L
Caccuri, F
Keele, BF
Foulds, KE
Shen, X
Tomaras, GD
Montefiori, DC
Roederer, M
Ferrari, G
Venzon, D
Stablien, D
Barouch, DH
Felber, BK
Pavlakis, GN
Michael, NL
Tartaglia, J
Franchini, G
AF Gordon, S. N.
Vaccari, M.
Doster, M. N.
Liyanage, N. P.
Pegu, P.
Schifanella, L.
Caccuri, F.
Keele, B. F.
Foulds, K. E.
Shen, X.
Tomaras, G. D.
Montefiori, D. C.
Roederer, M.
Ferrari, G.
Venzon, D.
Stablien, D.
Barouch, D. H.
Felber, B. K.
Pavlakis, G. N.
Michael, N. L.
Tartaglia, J.
Franchini, G.
TI Priming with Adenovirus26 Vaccines Affects ALVAC-SIV/gp120 Vaccine
Efficacy Tested in a SIVmac251 Challenge Model Performed One-Month
Post-Vaccination
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT Conference on AIDS Vaccine
CY OCT 07-10, 2013
CL Barcelona, SPAIN
C1 [Gordon, S. N.; Vaccari, M.; Doster, M. N.; Liyanage, N. P.; Pegu, P.; Schifanella, L.; Caccuri, F.; Venzon, D.; Felber, B. K.; Pavlakis, G. N.; Franchini, G.] NCI, NIH, Bethesda, MD 20892 USA.
[Keele, B. F.] NCI, SAIC Frederick, NIH, Frederick, MD 21701 USA.
[Foulds, K. E.; Roederer, M.] NIAID, NIH, Bethesda, MD 20892 USA.
[Shen, X.; Tomaras, G. D.] Duke Human Vaccine Inst, Durham, NC USA.
[Montefiori, D. C.; Ferrari, G.] Duke Univ, Med Ctr, Durham, NC USA.
[Stablien, D.] EMMES Corp, Rockville, MD USA.
[Barouch, D. H.] Beth Israel Deaconess Med Ctr, Boston, MD USA.
[Michael, N. L.] Walter Reed Army Inst Res, US Mil HIV Res Program, Silver Spring, MD USA.
[Tartaglia, J.] Sanofi Pasteur, Swiftwater, PA USA.
RI Tomaras, Georgia/J-5041-2016
NR 0
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 2013
VL 29
IS 11
SI SI
BP A39
EP A39
PG 1
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 239PI
UT WOS:000326037500092
ER
PT J
AU Gorman, J
Doria-Rose, N
Schramm, CA
Moore, PL
Pancera, M
Yang, Y
Staupe, RP
Zhang, Z
Georgiev, IS
Bhiman, J
Longo, NL
Morris, L
Shapiro, L
Mascola, JR
Kwong, PD
AF Gorman, J.
Doria-Rose, N.
Schramm, C. A.
Moore, P. L.
Pancera, M.
Yang, Y.
Staupe, R. P.
Zhang, Z.
Georgiev, I. S.
Bhiman, J.
Longo, N. L.
Morris, L.
Shapiro, L.
Mascola, J. R.
Kwong, P. D.
TI Structural Characterization of Potent, Longitudinally-Defined HIV-1
V1/V2-Directed Antibodies
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT Conference on AIDS Vaccine
CY OCT 07-10, 2013
CL Barcelona, SPAIN
C1 [Gorman, J.; Doria-Rose, N.; Pancera, M.; Yang, Y.; Staupe, R. P.; Georgiev, I. S.; Longo, N. L.; Mascola, J. R.; Kwong, P. D.] NIAID, NIH, Bethesda, MD 20892 USA.
[Schramm, C. A.; Zhang, Z.; Shapiro, L.] Columbia Univ, New York, NY USA.
[Moore, P. L.; Bhiman, J.; Morris, L.] Natl Hlth Lab Serv, Natl Inst Communicable Dis, Johannesburg, South Africa.
NR 0
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 2013
VL 29
IS 11
SI SI
BP A12
EP A12
PG 1
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 239PI
UT WOS:000326037500023
ER
PT J
AU Hammer, S
Sobieszczyk, M
Janes, H
Gilbert, P
Karuna, S
Grove, D
Ramirez, S
Bentley, C
Anude, C
Mulligan, M
Koblin, B
Buchbinder, S
Keefer, M
Hural, J
McElrath, J
Frahm, N
Tomaras, G
Graham, B
Enama, M
Broder, G
Maynard, J
Wakefield, S
Holt, R
DeJesus, E
Frank, I
Novak, R
Martinez, A
Kublin, J
Corey, L
AF Hammer, S.
Sobieszczyk, M.
Janes, H.
Gilbert, P.
Karuna, S.
Grove, D.
Ramirez, S.
Bentley, C.
Anude, C.
Mulligan, M.
Koblin, B.
Buchbinder, S.
Keefer, M.
Hural, J.
McElrath, J.
Frahm, N.
Tomaras, G.
Graham, B.
Enama, M.
Broder, G.
Maynard, J.
Wakefield, S.
Holt, R.
DeJesus, E.
Frank, I.
Novak, R.
Martinez, A.
Kublin, J.
Corey, L.
CA HIV Vaccine Trials Network
TI HVTN 505: Efficacy of a Multi-Gene DNA Prime/Recombinant Adeno 5 (rAd5)
Vector Boost Vaccine in Men & Transgender Women (TGW) Who Have Sex with
Men
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT Conference on AIDS Vaccine
CY OCT 07-10, 2013
CL Barcelona, SPAIN
C1 [Hammer, S.; Sobieszczyk, M.; HIV Vaccine Trials Network] Columbia Univ, New York, NY USA.
[Janes, H.; Gilbert, P.; Grove, D.] Fred Hutchinson Canc Res Ctr, SCHARP, Seattle, WA 98104 USA.
[Karuna, S.; Ramirez, S.; Bentley, C.; Hural, J.; McElrath, J.; Frahm, N.; Broder, G.; Maynard, J.; Wakefield, S.; Holt, R.; Kublin, J.; Corey, L.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Anude, C.; Martinez, A.] NIAID, DAIDS, Bethesda, MD 20892 USA.
[Mulligan, M.] Emory Univ, Atlanta, GA 30322 USA.
[Koblin, B.] New York Blood Ctr, New York, NY 10021 USA.
[Buchbinder, S.] San Francisco Dept Publ Hlth, San Francisco, CA USA.
[Keefer, M.] Univ Rochester, Rochester, NY USA.
[Tomaras, G.] Duke Univ, Durham, NC USA.
[Graham, B.; Enama, M.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[DeJesus, E.] Orlando Immunol Ctr, Orlando, FL USA.
[Frank, I.] Univ Penn, Philadelphia, PA 19104 USA.
[Novak, R.] Univ Illinois, Chicago, IL USA.
RI Tomaras, Georgia/J-5041-2016
NR 0
TC 0
Z9 0
U1 0
U2 4
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 2013
VL 29
IS 11
SI SI
BP A172
EP A172
PG 1
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 239PI
UT WOS:000326037500450
ER
PT J
AU Heeney, JL
Wagner, R
Esteban, M
Jacobs, B
Foulds, K
Roederer, M
Self, S
Barnett, S
Phogat, S
Montefiori, D
Tomaris, G
Pantaleo, G
AF Heeney, J. L.
Wagner, R.
Esteban, M.
Jacobs, B.
Foulds, K.
Roederer, M.
Self, S.
Barnett, S.
Phogat, S.
Montefiori, D.
Tomaris, G.
Pantaleo, G.
TI Rapid Appearance of Vaccine-Induced Potentially Protective Anti-Env
Antibody Responses with Early Co-administration of gp120 with NYVAC or
DNA
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT Conference on AIDS Vaccine
CY OCT 07-10, 2013
CL Barcelona, SPAIN
C1 [Heeney, J. L.] Univ Cambridge, Cambridge, England.
[Wagner, R.] Univ Regensburg, D-93053 Regensburg, Germany.
[Esteban, M.] CSIC, Ctr Nacl Biotecnol, Madrid, Spain.
[Jacobs, B.] Arizona State Univ, Tempe, AZ USA.
[Foulds, K.; Roederer, M.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Self, S.] Fred Hutchinson Canc Res Ctr, SCHARP, Seattle, WA 98104 USA.
[Barnett, S.] Novartis Vaccines & Diagnost Inc, Cambridge, MA USA.
[Phogat, S.] Sanofi Pasteur, Swiftwater, PA USA.
[Montefiori, D.; Tomaris, G.] Duke Univ, Med Ctr, Durham, NC USA.
[Pantaleo, G.] CHU Vaudois, CH-1011 Lausanne, Switzerland.
RI Pantaleo, Giuseppe/K-6163-2016
NR 0
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 2013
VL 29
IS 11
SI SI
BP A162
EP A163
PG 2
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 239PI
UT WOS:000326037500425
ER
PT J
AU Heeney, JL
Jacobs, B
Esteban, M
Wagner, R
Foulds, K
Roederer, M
Self, S
Barnett, S
Tartaglia, J
Montefiori, D
Tomaras, G
Pantaleo, G
AF Heeney, J. L.
Jacobs, B.
Esteban, M.
Wagner, R.
Foulds, K.
Roederer, M.
Self, S.
Barnett, S.
Tartaglia, J.
Montefiori, D.
Tomaras, G.
Pantaleo, G.
TI Increased HIV-1 Immunogenicity of Replication Competent NYVAC
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT Conference on AIDS Vaccine
CY OCT 07-10, 2013
CL Barcelona, SPAIN
C1 [Heeney, J. L.] Univ Cambridge, Cambridge, England.
[Jacobs, B.] Arizona State Univ, Tempe, AZ USA.
[Esteban, M.] CSIC, Ctr Nacl Biotecnol, Madrid, Spain.
[Wagner, R.] Univ Regensburg, D-93053 Regensburg, Germany.
[Foulds, K.; Roederer, M.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Self, S.] Fred Hutchinson Canc Res Ctr, SCHARP, Seattle, WA 98104 USA.
[Barnett, S.] Novartis Vaccines & Diagnost Inc, Cambridge, MA USA.
[Tartaglia, J.] Sanofi Pasteur, Swiftwater, PA USA.
[Montefiori, D.] Univ Med Ctr, Durham, NC USA.
[Tomaras, G.] Duke Univ, Med Ctr, Durham, NC USA.
[Pantaleo, G.] CHU Vaudois, CH-1011 Lausanne, Switzerland.
RI Tomaras, Georgia/J-5041-2016; Pantaleo, Giuseppe/K-6163-2016
NR 0
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 0889-2229
EI 1931-8405
J9 AIDS RES HUM RETROV
JI Aids Res. Hum. Retrovir.
PD NOV 1
PY 2013
VL 29
IS 11
SI SI
BP A160
EP A160
PG 1
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 239PI
UT WOS:000326037500418
ER
PT J
AU Heit, A
Schmitz, F
Moore, M
Gerdts, S
Spearman, P
Barnett, S
Graham, B
Robinson, H
Astronomo, R
Andersen-Nissen, E
Frahm, N
De Rosa, S
McElrath, M
AF Heit, A.
Schmitz, F.
Moore, M.
Gerdts, S.
Spearman, P.
Barnett, S.
Graham, B.
Robinson, H.
Astronomo, R.
Andersen-Nissen, E.
Frahm, N.
De Rosa, S.
McElrath, M.
TI HVTN-Tested Candidate HIV Vaccines Induce Early, Antigen-Specific
Plasmablast- and Tfh-like Responses in Peripheral Blood
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT Conference on AIDS Vaccine
CY OCT 07-10, 2013
CL Barcelona, SPAIN
C1 [Heit, A.; Moore, M.; Gerdts, S.; Astronomo, R.; Andersen-Nissen, E.; Frahm, N.; De Rosa, S.; McElrath, M.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Schmitz, F.] Seattle Biomed Res Inst, Seattle, WA 98109 USA.
[Spearman, P.] Emory Univ, Sch Med, Atlanta, GA USA.
[Barnett, S.] Novartis Vaccines & Diagnost, Cambridge, MA USA.
[Graham, B.] NIH, Bethesda, MD 20892 USA.
[Robinson, H.] GeoVax Inc, Atlanta, GA USA.
NR 0
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 0889-2229
EI 1931-8405
J9 AIDS RES HUM RETROV
JI Aids Res. Hum. Retrovir.
PD NOV 1
PY 2013
VL 29
IS 11
SI SI
BP A143
EP A144
PG 2
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 239PI
UT WOS:000326037500375
ER
PT J
AU Hu, H
Eller, M
Zafar, S
Currier, J
Marovich, M
Robb, M
Kim, J
Michael, N
Ratto-Kim, S
AF Hu, H.
Eller, M.
Zafar, S.
Currier, J.
Marovich, M.
Robb, M.
Kim, J.
Michael, N.
Ratto-Kim, S.
TI Adenovirus 5 Hexon-Specific CD4 T Cells Are More Susceptible to HIV and
Preferentially Depleted During Infection Compared to CMV-Specific CD4 T
Cells
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT Conference on AIDS Vaccine
CY OCT 07-10, 2013
CL Barcelona, SPAIN
C1 [Hu, H.; Eller, M.; Zafar, S.; Currier, J.; Robb, M.; Kim, J.; Michael, N.; Ratto-Kim, S.] US MHRP, Silver Spring, MD USA.
[Marovich, M.] NIAID, NIH, Bethesda, MD 20892 USA.
NR 0
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 0889-2229
EI 1931-8405
J9 AIDS RES HUM RETROV
JI Aids Res. Hum. Retrovir.
PD NOV 1
PY 2013
VL 29
IS 11
SI SI
BP A183
EP A183
PG 1
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 239PI
UT WOS:000326037500479
ER
PT J
AU Hural, J
Walsh, S
Moodie, Z
Frahm, N
Gartland, A
Friedrich, D
Hertz, T
Ahmed, H
Wilck, M
Morgan, C
Swann, E
Wang, H
Manso, B
Self, S
Graham, B
Jin, X
AF Hural, J.
Walsh, S.
Moodie, Z.
Frahm, N.
Gartland, A.
Friedrich, D.
Hertz, T.
Ahmed, H.
Wilck, M.
Morgan, C.
Swann, E.
Wang, H.
Manso, B.
Self, S.
Graham, B.
Jin, X.
TI Vaccination with Heterologous HIV Envelope Sequences and Heterologous
Adenovirus Vectors Increases T Cell Responses to Conserved Regions: HVTN
083
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT Conference on AIDS Vaccine
CY OCT 07-10, 2013
CL Barcelona, SPAIN
C1 [Hural, J.; Moodie, Z.; Frahm, N.; Gartland, A.; Friedrich, D.; Hertz, T.; Ahmed, H.; Morgan, C.; Wang, H.; Manso, B.; Self, S.] HIV Vaccine Trials Network, Seattle, WA USA.
[Walsh, S.] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Wilck, M.] Hosp Univ Penn, Philadelphia, PA 19104 USA.
[Swann, E.] NIAID, NIH, Bethesda, MD 20892 USA.
[Graham, B.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Jin, X.] Univ Rochester, Rochester, NY USA.
NR 0
TC 0
Z9 0
U1 1
U2 4
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 2013
VL 29
IS 11
SI SI
BP A172
EP A173
PG 2
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 239PI
UT WOS:000326037500451
ER
PT J
AU Jensen, K
Wilson, RL
Piatak, M
Lifson, JD
Ranangathan, UD
Jacobs, WR
Fennelly, G
Larsen, M
Van Rompay, KK
Kozlowski, PA
Abel, K
AF Jensen, K.
Wilson, R. L.
Piatak, M.
Lifson, J. D.
Ranangathan, U. D.
Jacobs, W. R.
Fennelly, G.
Larsen, M.
Van Rompay, K. K.
Kozlowski, P. A.
Abel, K.
TI Vaccine-Induced Intestinal and Salivary IgA Correlates with Reduced SIV
Viremia in Orally-Challenged Neonatal Macaques
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT Conference on AIDS Vaccine
CY OCT 07-10, 2013
CL Barcelona, SPAIN
C1 [Wilson, R. L.; Kozlowski, P. A.] Louisiana State Univ, Hlth Sci Ctr, New Orleans, LA USA.
[Piatak, M.; Lifson, J. D.] Frederick Natl Lab Canc Res, Frederick, MD USA.
[Ranangathan, U. D.; Jacobs, W. R.; Fennelly, G.; Larsen, M.] Albert Einstein Coll Med, New York, NY USA.
[Van Rompay, K. K.] Univ Calif Davis, CNPRC, Davis, CA USA.
[Jensen, K.; Abel, K.] Univ N Carolina, Chapel Hill, NC USA.
NR 0
TC 0
Z9 0
U1 0
U2 3
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 2013
VL 29
IS 11
SI SI
BP A104
EP A104
PG 1
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 239PI
UT WOS:000326037500265
ER
PT J
AU Joachim, A
Munseri, P
Nilsson, C
Bakari, M
Aboud, S
Lyamuya, EF
Moshiro, C
Robb, M
Marovich, M
Earl, P
Moss, B
Buma, D
Janabi, M
Wahren, B
Mhalu, F
Ferrari, G
Sandstrom, E
Biberfeld, G
AF Joachim, A.
Munseri, P.
Nilsson, C.
Bakari, M.
Aboud, S.
Lyamuya, E. F.
Moshiro, C.
Robb, M.
Marovich, M.
Earl, P.
Moss, B.
Buma, D.
Janabi, M.
Wahren, B.
Mhalu, F.
Ferrari, G.
Sandstrom, E.
Biberfeld, G.
TI A Late Third HIV-MVA Vaccination Boosted Strong and Potent Immune
Responses in Tanzanian Volunteers Previously Immunized with HIV-DNA and
HIV-MVA
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT Conference on AIDS Vaccine
CY OCT 07-10, 2013
CL Barcelona, SPAIN
C1 [Joachim, A.; Munseri, P.] Muhimbili Univ Hlth & Allied Sci, Stockholm, Sweden.
[Joachim, A.; Munseri, P.; Nilsson, C.] Karolinska Inst, Stockholm, Sweden.
[Joachim, A.; Munseri, P.; Bakari, M.; Aboud, S.; Lyamuya, E. F.; Moshiro, C.; Biberfeld, G.] Muhimbili Univ Hlth & Allied Sci, Dar Es Salaam, Tanzania.
[Joachim, A.; Munseri, P.] Karolinska Inst, Dar Es Salaam, Tanzania.
[Nilsson, C.] Swedish Inst communicable Dis Solna, Stockholm, Sweden.
[Robb, M.; Marovich, M.] US MHRP, Silver Spring, MD USA.
[Earl, P.; Moss, B.] NIAID, NIH, Bethesda, MD 20892 USA.
[Buma, D.; Janabi, M.; Mhalu, F.] Muhimbili Natl Hosp, Dar Es Salaam, Tanzania.
[Wahren, B.; Sandstrom, E.] Karolinska Inst, Stockholm, Sweden.
[Ferrari, G.] Duke Univ, Med Ctr, Durham, NC USA.
NR 0
TC 0
Z9 0
U1 0
U2 3
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 2013
VL 29
IS 11
SI SI
BP A174
EP A174
PG 1
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 239PI
UT WOS:000326037500455
ER
PT J
AU Klatt, N
Bosinger, S
Heigele, A
Lederman, M
Juelg, B
Camerini, D
Torti, C
Martin, J
Deeks, S
Sinclari, E
Brenchley, J
Paiardini, M
Hecht, F
Kirchhoff, F
Hunt, P
Silvestri, G
AF Klatt, N.
Bosinger, S.
Heigele, A.
Lederman, M.
Juelg, B.
Camerini, D.
Torti, C.
Martin, J.
Deeks, S.
Sinclari, E.
Brenchley, J.
Paiardini, M.
Hecht, F.
Kirchhoff, F.
Hunt, P.
Silvestri, G.
TI Limited HIV Infection of Central Memory CD4+T Cells Is Associated with
Lack of Progression in Viremic Individuals
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT Conference on AIDS Vaccine
CY OCT 07-10, 2013
CL Barcelona, SPAIN
C1 [Klatt, N.] Univ Washington, Seattle, WA 98195 USA.
[Bosinger, S.; Paiardini, M.; Silvestri, G.] Emory Univ, Atlanta, GA 30322 USA.
[Heigele, A.; Kirchhoff, F.] Univ Ulm, Med Ctr, D-89069 Ulm, Germany.
[Lederman, M.] Case Western Reserve Univ, Cleveland, OH 44106 USA.
[Juelg, B.] Ragon Inst MGH MIT & Harvard, Cambridge, MA USA.
[Camerini, D.] Univ Calif Irvine, Irvine, CA USA.
[Torti, C.] Univ Brescia, Brescia, Italy.
[Martin, J.; Deeks, S.; Sinclari, E.; Hecht, F.; Hunt, P.] UCSF Posit Hlth Program, San Francisco, CA USA.
[Brenchley, J.] NIAID, NIH, LMM, Bethesda, MD 20892 USA.
NR 0
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 0889-2229
EI 1931-8405
J9 AIDS RES HUM RETROV
JI Aids Res. Hum. Retrovir.
PD NOV 1
PY 2013
VL 29
IS 11
SI SI
BP A128
EP A128
PG 1
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 239PI
UT WOS:000326037500332
ER
PT J
AU Krebs, SJ
Narpala, S
Wheatley, A
Slike, BM
Eller, M
Ratto-Kim, S
Polonis, VR
Kim, JH
Robb, ML
Marovich, MA
Koup, RA
Graham, BS
Michael, NL
McDermott, A
AF Krebs, S. J.
Narpala, S.
Wheatley, A.
Slike, B. M.
Eller, M.
Ratto-Kim, S.
Polonis, V. R.
Kim, J. H.
Robb, M. L.
Marovich, M. A.
Koup, R. A.
Graham, B. S.
Michael, N. L.
McDermott, A.
TI Comparative Analysis of Binding Antibody Responses Elicited by a
Cross-Section of Human HIV-1 Vaccine Clinical Trials
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT Conference on AIDS Vaccine
CY OCT 07-10, 2013
CL Barcelona, SPAIN
C1 [Krebs, S. J.; Slike, B. M.; Eller, M.; Ratto-Kim, S.; Polonis, V. R.; Kim, J. H.; Robb, M. L.; Marovich, M. A.; Michael, N. L.] Walter Reed Army Inst Res, US Mil HIV Res Program, Silver Spring, MD USA.
[Krebs, S. J.; Slike, B. M.; Eller, M.; Ratto-Kim, S.; Robb, M. L.] Henry M Jackson Fdn Adv Mil Med, Silver Spring, MD USA.
[Narpala, S.; Wheatley, A.; Koup, R. A.; Graham, B. S.; McDermott, A.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
NR 0
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 0889-2229
EI 1931-8405
J9 AIDS RES HUM RETROV
JI Aids Res. Hum. Retrovir.
PD NOV 1
PY 2013
VL 29
IS 11
SI SI
BP A8
EP A9
PG 2
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 239PI
UT WOS:000326037500014
ER
PT J
AU Kuwata, T
Takaki, K
Yoshimura, K
Enomoto, I
Wu, F
Ourmanov, I
Hirsch, VM
Yokoyama, M
Sato, H
Matsushita, S
AF Kuwata, T.
Takaki, K.
Yoshimura, K.
Enomoto, I.
Wu, F.
Ourmanov, I.
Hirsch, V. M.
Yokoyama, M.
Sato, H.
Matsushita, S.
TI Analysis of Env Regions Important for Binding and Resistance to B404, a
Potent Neutralizing Antibody Against SIV
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT Conference on AIDS Vaccine
CY OCT 07-10, 2013
CL Barcelona, SPAIN
C1 [Kuwata, T.; Takaki, K.; Enomoto, I.; Matsushita, S.] Kumamoto Univ, Kumamoto, Japan.
[Wu, F.; Ourmanov, I.; Hirsch, V. M.] NIAID, LMM, NIH, Bethesda, MD 20892 USA.
NR 0
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 2013
VL 29
IS 11
SI SI
BP A57
EP A57
PG 1
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 239PI
UT WOS:000326037500141
ER
PT J
AU Liang, F
Sandgren, KJ
Lindgren, G
Thompson, EA
Fausther-Bovendo, H
O'Hagan, D
Seubert, A
De Gregorio, E
Rao, S
Sullivan, NJ
Seder, RA
Koup, RA
Lore, K
AF Liang, F.
Sandgren, K. J.
Lindgren, G.
Thompson, E. A.
Fausther-Bovendo, H.
O'Hagan, D.
Seubert, A.
De Gregorio, E.
Rao, S.
Sullivan, N. J.
Seder, R. A.
Koup, R. A.
Lore, K.
TI Vaccine Adjuvants Induce Distinct Innate Immune Activation Profiles In
Vivo
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT Conference on AIDS Vaccine
CY OCT 07-10, 2013
CL Barcelona, SPAIN
C1 [Thompson, E. A.; Fausther-Bovendo, H.; Rao, S.; Sullivan, N. J.; Seder, R. A.; Koup, R. A.] NIH, Bethesda, MD 20892 USA.
[O'Hagan, D.; Seubert, A.; De Gregorio, E.] Novartis Vaccines & Diagnost, Cambridge, MA USA.
[Liang, F.; Sandgren, K. J.; Lindgren, G.; Lore, K.] Karolinska Inst, Stockholm, Sweden.
NR 0
TC 0
Z9 0
U1 0
U2 3
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 2013
VL 29
IS 11
SI SI
BP A94
EP A94
PG 1
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 239PI
UT WOS:000326037500239
ER
PT J
AU Lifson, JD
Del Prete, GQ
Moldt, B
Keele, BF
Estes, JD
Oswald, K
Fast, R
Trubey, CM
Smedley, J
Burton, DR
KewalRamani, V
Piatak, M
Bieniasz, P
Hatziioannou, T
AF Lifson, J. D.
Del Prete, G. Q.
Moldt, B.
Keele, B. F.
Estes, J. D.
Oswald, K.
Fast, R.
Trubey, C. M.
Smedley, J.
Burton, D. R.
KewalRamani, V.
Piatak, M., Jr.
Bieniasz, P.
Hatziioannou, T.
TI Novel R5 Tropic Founder Env SHIV for Nonhuman Primate Immunoprophylactic
Studies
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT Conference on AIDS Vaccine
CY OCT 07-10, 2013
CL Barcelona, SPAIN
C1 [Lifson, J. D.; Del Prete, G. Q.; Keele, B. F.; Estes, J. D.; Oswald, K.; Fast, R.; Trubey, C. M.; Smedley, J.; Piatak, M., Jr.] SAIC Frederick Inc, Frederick Natl Lab, Frederick, MD USA.
[Moldt, B.; Burton, D. R.] Scripps Res Inst, La Jolla, CA 92037 USA.
[KewalRamani, V.] NCI, Frederick, MD 21701 USA.
[Bieniasz, P.; Hatziioannou, T.] Rockefeller Univ, New York, NY 10021 USA.
NR 0
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 2013
VL 29
IS 11
SI SI
BP A185
EP A186
PG 2
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 239PI
UT WOS:000326037500484
ER
PT J
AU Liyanage, NP
Gordon, SN
Vaccari, M
Pegu, P
Doster, MN
Tomaras, GD
Venzon, D
Stablien, D
Tartaglia, J
Barnett, SW
Kim, JH
Michael, NL
Franchini, G
AF Liyanage, N. P.
Gordon, S. N.
Vaccari, M.
Pegu, P.
Doster, M. N.
Tomaras, G. D.
Venzon, D.
Stablien, D.
Tartaglia, J.
Barnett, S. W.
Kim, J. H.
Michael, N. L.
Franchini, G.
TI Alum and MF59, in Combination with ALVAC-SIV and Gp120 Vaccines Recruit
Functionally Different NK Cells to the Gut of Vaccinated Rhesus Macaque
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT Conference on AIDS Vaccine
CY OCT 07-10, 2013
CL Barcelona, SPAIN
C1 [Liyanage, N. P.; Gordon, S. N.; Vaccari, M.; Pegu, P.; Doster, M. N.; Franchini, G.] NCI, Bethesda, MD 20892 USA.
[Tomaras, G. D.] Duke Human Vaccine Inst, Durham, NC USA.
[Venzon, D.] NCI, NIH, Bethesda, MD 20892 USA.
[Stablien, D.] EMMES Corp, Rockville, MD USA.
[Tartaglia, J.] Sanofi Pasteur, Swiftwater, PA USA.
[Barnett, S. W.] Novartis Vaccines & Diagnost Inc, Cambridge, MA USA.
[Kim, J. H.; Michael, N. L.] Walter Reed Army Inst Res, Silver Spring, MD USA.
RI Tomaras, Georgia/J-5041-2016
NR 0
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 2013
VL 29
IS 11
SI SI
BP A100
EP A100
PG 1
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 239PI
UT WOS:000326037500255
ER
PT J
AU Lynch, RM
Wong, P
Wu, X
Mascola, J
AF Lynch, R. M.
Wong, P.
Wu, X.
Mascola, J.
TI Fitness Cost of Viral Escape from Broadly Neutralizing CD4-Binding Site
Antibodies
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT Conference on AIDS Vaccine
CY OCT 07-10, 2013
CL Barcelona, SPAIN
C1 [Lynch, R. M.; Wong, P.; Mascola, J.] NIH, Bethesda, MD 20892 USA.
[Wu, X.] Aaron Diamond AIDS Res Ctr, New York, NY USA.
NR 0
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 2013
VL 29
IS 11
SI SI
BP A62
EP A62
PG 1
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 239PI
UT WOS:000326037500154
ER
PT J
AU Mackelprang, R
Carrington, M
Thomas, K
Hughes, JP
Baeten, JM
Wald, A
Farquhar, C
Fife, K
Campbell, MS
Kapiga, S
Mullins, JI
Lingappa, JR
AF Mackelprang, R.
Carrington, M.
Thomas, K.
Hughes, J. P.
Baeten, J. M.
Wald, A.
Farquhar, C.
Fife, K.
Campbell, M. S.
Kapiga, S.
Mullins, J. I.
Lingappa, J. R.
TI Host and Viral Factors Associated with HIV-1 RNA Set-Point Among HIV-1
Seroconverters from sub- Saharan Africa
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT Conference on AIDS Vaccine
CY OCT 07-10, 2013
CL Barcelona, SPAIN
C1 [Mackelprang, R.; Thomas, K.; Hughes, J. P.; Baeten, J. M.; Wald, A.; Farquhar, C.; Campbell, M. S.; Kapiga, S.; Mullins, J. I.; Lingappa, J. R.] Univ Washington, Seattle, WA 98195 USA.
[Carrington, M.] NCI, Frederick, MD 21701 USA.
[Fife, K.] Indiana Univ, Bloomington, IN USA.
NR 0
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 0889-2229
EI 1931-8405
J9 AIDS RES HUM RETROV
JI Aids Res. Hum. Retrovir.
PD NOV 1
PY 2013
VL 29
IS 11
SI SI
BP A179
EP A179
PG 1
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 239PI
UT WOS:000326037500468
ER
PT J
AU Mann, P
Kosgei, J
Sekiziyivu, A
Sawe, F
Maboko, L
Kibuuka, H
Tong, T
Karasavva, N
Robb, M
Eller, L
Ake, J
Marovich, M
Ngauy, V
AF Mann, P.
Kosgei, J.
Sekiziyivu, A.
Sawe, F.
Maboko, L.
Kibuuka, H.
Tong, T.
Karasavva, N.
Robb, M.
Eller, L.
Ake, J.
Marovich, M.
Ngauy, V.
TI Acceptability and Tolerability of Novel Mucosal Secretion Collection
Methods in an HIV Vaccine Trial in East Africa
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT Conference on AIDS Vaccine
CY OCT 07-10, 2013
CL Barcelona, SPAIN
C1 [Mann, P.; Maboko, L.] Natl Inst Med Res, Mbeya Med Res Ctr, Mbeya, Tanzania.
[Kosgei, J.; Sawe, F.] Kenya Govt Med Res Ctr, Walter Reed Project, Kericho, Kenya.
[Sekiziyivu, A.; Kibuuka, H.] Makerere Univ, Walter Reed Project, Kampala, Uganda.
[Tong, T.; Robb, M.; Eller, L.; Ake, J.] US Mil HIV Res Program, Rockville, MD USA.
[Karasavva, N.; Ngauy, V.] Armed Forces Res Inst Med Sci, Bangkok 10400, Thailand.
[Marovich, M.] NIAID, Div Aids, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
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 2013
VL 29
IS 11
SI SI
BP A142
EP A142
PG 1
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 239PI
UT WOS:000326037500371
ER
PT J
AU Mason, R
Welles, H
Schmidt, S
Chakrabarti, B
Yang, Z
Saunders, K
Mascola, J
Roederer, M
AF Mason, R.
Welles, H.
Schmidt, S.
Chakrabarti, B.
Yang, Z.
Saunders, K.
Mascola, J.
Roederer, M.
TI Characterization of Antibodies Targeting the Receptor and Co-receptor
Binding Region of SIV Envelope
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT Conference on AIDS Vaccine
CY OCT 07-10, 2013
CL Barcelona, SPAIN
C1 [Mason, R.; Welles, H.; Schmidt, S.; Yang, Z.; Saunders, K.; Mascola, J.; Roederer, M.] NIAID, NIH, Bethesda, MD 20892 USA.
[Chakrabarti, B.] Scripps Res Inst, La Jolla, CA 92037 USA.
NR 0
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 2013
VL 29
IS 11
SI SI
BP A37
EP A38
PG 2
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 239PI
UT WOS:000326037500087
ER
PT J
AU Migueles, SA
Zimmerman, MG
Mendoza, D
Toulmin, SA
Kelly, EP
Connors, M
AF Migueles, S. A.
Zimmerman, M. G.
Mendoza, D.
Toulmin, S. A.
Kelly, E. P.
Connors, M.
TI Increased Cytotoxic Capacity of Immunodominant HIV-Specific CD8+T-Cell
Responses Is Associated with Immune Control Regardless of HLA Type
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT Conference on AIDS Vaccine
CY OCT 07-10, 2013
CL Barcelona, SPAIN
C1 [Migueles, S. A.; Zimmerman, M. G.; Mendoza, D.; Toulmin, S. A.; Kelly, E. P.; Connors, M.] NIAID, NIH, Bethesda, MD 20892 USA.
NR 0
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 2013
VL 29
IS 11
SI SI
BP A125
EP A125
PG 1
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 239PI
UT WOS:000326037500323
ER
PT J
AU Murillo, PAM
Sundling, C
Feng, Y
O'Dell, S
Reimann, K
Mascola, J
Wyatt, R
Hedestam, GBK
AF Murillo, P. A. Martinez
Sundling, C.
Feng, Y.
O'Dell, S.
Reimann, K.
Mascola, J.
Wyatt, R.
Hedestam, G. B. Karlsson
TI Impact of TLR9 Stimulation on HIV-1 Env-Specific Immune Responses
Elicited in Non-human Primates
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT Conference on AIDS Vaccine
CY OCT 07-10, 2013
CL Barcelona, SPAIN
C1 [Murillo, P. A. Martinez; Sundling, C.; Hedestam, G. B. Karlsson] Karolinska Inst, Stockholm, Sweden.
[Feng, Y.; Wyatt, R.] Scripps Res Inst, IAVI Neutralizing Antibody Ctr, La Jolla, CA 92037 USA.
[O'Dell, S.; Mascola, J.] NIH, Bethesda, MD 20892 USA.
[Reimann, K.] Univ Massachusetts, Sch Med, Boston, MA 02125 USA.
RI Feng, Yu/A-3396-2012
NR 0
TC 0
Z9 0
U1 0
U2 2
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 2013
VL 29
IS 11
SI SI
BP A7
EP A7
PG 1
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 239PI
UT WOS:000326037500011
ER
PT J
AU Navis, M
Tran, K
Li, Y
Phad, G
Sundling, C
Wilson, R
Soldemo, M
McKee, K
Mascola, J
Wyatt, RT
Hedestam, GBK
AF Navis, M.
Tran, K.
Li, Y.
Phad, G.
Sundling, C.
Wilson, R.
Soldemo, M.
McKee, K.
Mascola, J.
Wyatt, R. T.
Hedestam, G. B. Karlsson
TI Vaccine-Elicited CD4 Binding Site-Directed Antibodies Utilizing the
Macaque Equivalent of the Human VH1-2 Heavy Chain Variable Gene Segment
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT Conference on AIDS Vaccine
CY OCT 07-10, 2013
CL Barcelona, SPAIN
C1 [Navis, M.; Phad, G.; Sundling, C.; Soldemo, M.; Hedestam, G. B. Karlsson] Karolinska Inst, Stockholm, Sweden.
[Tran, K.; Li, Y.; Wilson, R.; Wyatt, R. T.] Scripps Res Inst, La Jolla, CA 92037 USA.
[McKee, K.; Mascola, J.] NIAID, NIH, Bethesda, MD 20892 USA.
NR 0
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 0889-2229
EI 1931-8405
J9 AIDS RES HUM RETROV
JI Aids Res. Hum. Retrovir.
PD NOV 1
PY 2013
VL 29
IS 11
SI SI
BP A41
EP A42
PG 2
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 239PI
UT WOS:000326037500098
ER
PT J
AU Nawaz, F
Cicala, C
Schwing, C
Wei, D
Hiatt, J
Jelicic, K
Van Ryk, D
Fauci, A
Arthos, J
AF Nawaz, F.
Cicala, C.
Schwing, C.
Wei, D.
Hiatt, J.
Jelicic, K.
Van Ryk, D.
Fauci, A.
Arthos, J.
TI A Role for Glycosylation in HIV Transmission
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT Conference on AIDS Vaccine
CY OCT 07-10, 2013
CL Barcelona, SPAIN
C1 [Nawaz, F.] NYU, New York, NY USA.
[Cicala, C.; Schwing, C.; Wei, D.; Hiatt, J.; Jelicic, K.; Van Ryk, D.; Fauci, A.; Arthos, J.] NIAID, Bethesda, MD 20892 USA.
NR 0
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 2013
VL 29
IS 11
SI SI
BP A15
EP A16
PG 2
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 239PI
UT WOS:000326037500033
ER
PT J
AU Ofek, G
Zirkle, B
Yang, Y
McKee, K
Zhu, Z
Louder, MK
Mascola, JR
Dimitrov, DS
Kwong, PD
AF Ofek, G.
Zirkle, B.
Yang, Y.
McKee, K.
Zhu, Z.
Louder, M. K.
Mascola, J. R.
Dimitrov, D. S.
Kwong, P. D.
TI Crystal Structure of the 2F5-like Antibody m66 in Complex with Its HIV-1
gp41 Epitope
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT Conference on AIDS Vaccine
CY OCT 07-10, 2013
CL Barcelona, SPAIN
C1 [Ofek, G.; Zirkle, B.; Yang, Y.; McKee, K.; Louder, M. K.; Mascola, J. R.; Kwong, P. D.] NIAID, NIH, Bethesda, MD 20892 USA.
[Zhu, Z.; Dimitrov, D. S.] NCI, NIH, Frederick, MD 21701 USA.
NR 0
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 2013
VL 29
IS 11
SI SI
BP A52
EP A52
PG 1
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 239PI
UT WOS:000326037500127
ER
PT J
AU Olvera, A
Llano, A
Rosati, M
Perez-Alvarez, S
Kulkarni, V
Chowdhury, B
Alicea, C
Beach, RK
Sardesai, NY
Hanke, T
Clotet, B
Pavlakis, GN
Felber, BK
Brander, C
Mothe, B
AF Olvera, A.
Llano, A.
Rosati, M.
Perez-Alvarez, S.
Kulkarni, V.
Chowdhury, B.
Alicea, C.
Beach, R. K.
Sardesai, N. Y.
Hanke, T.
Clotet, B.
Pavlakis, G. N.
Felber, B. K.
Brander, C.
Mothe, B.
TI DNA-MVA Prime-Boost Vaccine Eliciting T-Cell Specificities Associated
with HIV-1 Control Is Highly Immunogenic in Mice and Breaks CTL
Immunodominance
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT Conference on AIDS Vaccine
CY OCT 07-10, 2013
CL Barcelona, SPAIN
C1 [Olvera, A.; Llano, A.; Perez-Alvarez, S.; Clotet, B.; Brander, C.; Mothe, B.] IrsiCaixa AIDS Res Inst HIVACAT, Badalona, Spain.
[Olvera, A.; Clotet, B.; Brander, C.] Lluita Sida Hosp Germans Trias & Pujol, Badalona, Spain.
[Rosati, M.; Kulkarni, V.; Chowdhury, B.; Alicea, C.; Beach, R. K.; Pavlakis, G. N.; Felber, B. K.] NCI, Frederick, MD 21701 USA.
[Sardesai, N. Y.] Inovio Pharmaceut Biomed Corp, Blue Bell, PA USA.
[Hanke, T.] Univ Oxford, Oxford OX1 2JD, England.
[Clotet, B.; Brander, C.] Univ Autonoma Barcelona, Badalona, Spain.
NR 0
TC 0
Z9 0
U1 0
U2 2
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 2013
VL 29
IS 11
SI SI
BP A15
EP A15
PG 1
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 239PI
UT WOS:000326037500031
ER
PT J
AU Pancera, M
Zhu, J
O'Dell, S
Yang, Y
Zhang, B
Changela, A
McLellan, JS
Wu, X
Zhou, T
Burton, DR
Koff, WC
Mascola, JR
Kwong, PD
AF Pancera, M.
Zhu, J.
O'Dell, S.
Yang, Y.
Zhang, B.
Changela, A.
McLellan, J. S.
Wu, X.
Zhou, T.
Burton, D. R.
Koff, W. C.
Mascola, J. R.
Kwong, P. D.
TI Arginine-Scanning of PG16 Paratope Defines Quaternary Epitope
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT Conference on AIDS Vaccine
CY OCT 07-10, 2013
CL Barcelona, SPAIN
C1 [Pancera, M.; Zhu, J.; O'Dell, S.; Yang, Y.; Zhang, B.; Changela, A.; McLellan, J. S.; Wu, X.; Zhou, T.; Burton, D. R.; Koff, W. C.; Mascola, J. R.; Kwong, P. D.] NIAID, NIH, VRC, Bethesda, MD 20892 USA.
RI Zhou, Tongqing/A-6880-2010
OI Zhou, Tongqing/0000-0002-3935-4637
NR 0
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 2013
VL 29
IS 11
SI SI
BP A59
EP A60
PG 2
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 239PI
UT WOS:000326037500148
ER
PT J
AU Pavlakis, GN
Jalah, R
Li, J
Valentin, A
Rosati, M
Patel, V
Kulkarni, V
Alicea, C
Beach, RK
Guan, Y
Lifson, JD
Hirsch, VM
Venzon, D
Broderick, KE
Sardesai, NY
Fouts, TR
Pinter, A
LaBranche, C
Montefiori, DC
Shen, S
Tomaras, GD
Felber, BK
AF Pavlakis, G. N.
Jalah, R.
Li, J.
Valentin, A.
Rosati, M.
Patel, V.
Kulkarni, V.
Alicea, C.
Beach, R. Kelly
Guan, Y.
Lifson, J. D.
Hirsch, V. M.
Venzon, D.
Broderick, K. E.
Sardesai, N. Y.
Fouts, T. R.
Pinter, A.
LaBranche, C.
Montefiori, D. C.
Shen, S.
Tomaras, G. D.
Felber, B. K.
TI Optimization of Systemic and Mucosal Immune Responses to SIV and HIV-1
Antigens Using Different Protocols of DNA and Protein Immunization in
Macaques
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT Conference on AIDS Vaccine
CY OCT 07-10, 2013
CL Barcelona, SPAIN
C1 [Pavlakis, G. N.; Jalah, R.; Li, J.; Valentin, A.; Rosati, M.; Patel, V.; Kulkarni, V.; Alicea, C.; Beach, R. Kelly; Venzon, D.; Felber, B. K.] NCI, Frederick, MD 21701 USA.
[Guan, Y.] Inst Human Virol, Baltimore, MD USA.
[Lifson, J. D.] SAIC Frederick Inc, Frederick, MD USA.
[Hirsch, V. M.] NIAID, Bethesda, MD 20892 USA.
[Broderick, K. E.; Sardesai, N. Y.] Inovio Pharmaceut Inc, Blue Bell, PA USA.
[Fouts, T. R.] Profectus BioSci Inc, Baltimore, MD USA.
[Pinter, A.] Univ Med & Dent New Jersey, Newark, NJ 07103 USA.
[LaBranche, C.; Montefiori, D. C.; Shen, S.; Tomaras, G. D.] Duke Univ, Med Ctr, Durham, NC USA.
RI Tomaras, Georgia/J-5041-2016; bebarta, vikhyat/K-3476-2015
NR 0
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 2013
VL 29
IS 11
SI SI
BP A19
EP A19
PG 1
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 239PI
UT WOS:000326037500042
ER
PT J
AU Penaloza-MacMaster, P
Wherry, EJ
Barber, DL
Teigler, JE
Provine, NM
Barouch, DH
AF Penaloza-MacMaster, P.
Wherry, E. J.
Barber, D. L.
Teigler, J. E.
Provine, N. M.
Barouch, D. H.
TI Memory CD4 T Cells Provide Help Following Acute Viral Challenge, but
Promote Lethal Immunopathology Following Chronic Viral Challenge
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT Conference on AIDS Vaccine
CY OCT 07-10, 2013
CL Barcelona, SPAIN
C1 [Penaloza-MacMaster, P.; Teigler, J. E.; Provine, N. M.] Harvard Univ, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA.
[Wherry, E. J.] Univ Penn, Philadelphia, PA 19104 USA.
[Barber, D. L.] NIAID, Bethesda, MD 20892 USA.
[Barouch, D. H.] Ragon Inst MGH MIT & Harvard, Cambridge, MA USA.
NR 0
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 2013
VL 29
IS 11
SI SI
BP A122
EP A122
PG 1
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 239PI
UT WOS:000326037500316
ER
PT J
AU Phad, GE
Sundling, C
Zhang, Z
Navis, M
O'Dell, S
Li, Y
Wyatt, R
Mascola, J
Shapiro, L
Hedestam, GBK
AF Phad, G. E.
Sundling, C.
Zhang, Z.
Navis, M.
O'Dell, S.
Li, Y.
Wyatt, R.
Mascola, J.
Shapiro, L.
Hedestam, G. B. Karlsson
TI Genetic and Functional Characterization of Somatic Variants of
Vaccine-Induced HIV-1 CD4bs-Directed Monoclonal Antibodies
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT Conference on AIDS Vaccine
CY OCT 07-10, 2013
CL Barcelona, SPAIN
C1 [Phad, G. E.; Sundling, C.; Navis, M.; Hedestam, G. B. Karlsson] Karolinska Inst, Stockholm, Sweden.
[Zhang, Z.; Shapiro, L.] Columbia Univ, New York, NY USA.
[O'Dell, S.; Mascola, J.] NIH, Bethesda, MD 20892 USA.
[Li, Y.; Wyatt, R.] Scripps Res Inst, La Jolla, CA 92037 USA.
NR 0
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 0889-2229
EI 1931-8405
J9 AIDS RES HUM RETROV
JI Aids Res. Hum. Retrovir.
PD NOV 1
PY 2013
VL 29
IS 11
SI SI
BP A58
EP A58
PG 1
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 239PI
UT WOS:000326037500144
ER
PT J
AU Redd, AD
Ssemwanga, D
Wendel, SK
Ndembi, N
Vandepitte, J
Grosskurth, H
Parry, CM
Martens, C
Bruno, D
Porcella, SF
Quinn, TC
Kaleebu, P
AF Redd, A. D.
Ssemwanga, D.
Wendel, S. K.
Ndembi, N.
Vandepitte, J.
Grosskurth, H.
Parry, C. M.
Martens, C.
Bruno, D.
Porcella, S. F.
Quinn, T. C.
Kaleebu, P.
TI Incidence of HIV-1 Superinfection Is Similar to Primary HIV-1 Incidence
in a Cohort of Female Sex Workers in Uganda
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT Conference on AIDS Vaccine
CY OCT 07-10, 2013
CL Barcelona, SPAIN
C1 [Redd, A. D.; Wendel, S. K.; Quinn, T. C.] NIAID, Immunoregulat Lab, NIH, Baltimore, MD USA.
[Ssemwanga, D.; Vandepitte, J.; Parry, C. M.; Kaleebu, P.] MRC UVRI Uganda Res Unit AIDS, Entebbe, Uganda.
[Ndembi, N.] Inst Human Virol, Abuja, Nigeria.
[Grosskurth, H.] London Sch Hyg & Trop Med, London WC1, England.
[Martens, C.; Bruno, D.; Porcella, S. F.] NIAID, Genom Unit, Res Technol Branch, Rocky Mt Labs,Div Intramural Res,NIH, Hamilton, MT USA.
NR 0
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 0889-2229
EI 1931-8405
J9 AIDS RES HUM RETROV
JI Aids Res. Hum. Retrovir.
PD NOV 1
PY 2013
VL 29
IS 11
SI SI
BP A77
EP A77
PG 1
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 239PI
UT WOS:000326037500193
ER
PT J
AU Reddy, K
Winkler, C
Werner, L
Mlisana, K
Abdool Karim, S
Ndung'u, T
AF Reddy, K.
Winkler, C.
Werner, L.
Mlisana, K.
Abdool Karim, S.
Ndung'u, T.
TI APOBEC3G and-3F Induced Cytidine Deamination and Association with Viral
Control in a Population with High Frequency of the APOBEC3G H186R
Variant
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT Conference on AIDS Vaccine
CY OCT 07-10, 2013
CL Barcelona, SPAIN
C1 [Reddy, K.] Univ KwaZulu Natal, Nelson R Mandela Sch Med, Durban, South Africa.
[Winkler, C.] NCI, Frederick, MD 21701 USA.
[Werner, L.; Mlisana, K.; Abdool Karim, S.; Ndung'u, T.] Univ KwaZulu Natal, CAPRISA, Durban, South Africa.
NR 0
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 2013
VL 29
IS 11
SI SI
BP A91
EP A91
PG 1
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 239PI
UT WOS:000326037500230
ER
PT J
AU Rolland, M
Edlefsen, PT
Gottardo, R
Montefiori, DC
Zolla-Pazner, S
Moody, A
Liao, LH
Liu, P
Tomaras, GD
Haynes, BF
Bailer, RT
Koup, RA
Mascola, JR
Shen, X
Korber, BT
Tovanabutra, S
Rerks-Ngarm, S
Nitayaphan, S
Pitisuttihum, P
Kaewkungwal, J
Robb, ML
Michael, NL
Mullins, JI
Gilbert, PB
Kim, JH
AF Rolland, M.
Edlefsen, P. T.
Gottardo, R.
Montefiori, D. C.
Zolla-Pazner, S.
Moody, A.
Liao, L. H.
Liu, P.
Tomaras, G. D.
Haynes, B. F.
Bailer, R. T.
Koup, R. A.
Mascola, J. R.
Shen, X.
Korber, B. T.
Tovanabutra, S.
Rerks-Ngarm, S.
Nitayaphan, S.
Pitisuttihum, P.
Kaewkungwal, J.
Robb, M. L.
Michael, N. L.
Mullins, J. I.
Gilbert, P. B.
Kim, J. H.
TI Genetic and Immunological Evidence for a Role of Env-V3 Antibodies in
the RV144 Trial
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT Conference on AIDS Vaccine
CY OCT 07-10, 2013
CL Barcelona, SPAIN
C1 [Rolland, M.; Tovanabutra, S.; Robb, M. L.; Michael, N. L.; Kim, J. H.] US MHRP, Silver Spring, MD USA.
[Edlefsen, P. T.; Gottardo, R.; Gilbert, P. B.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Montefiori, D. C.; Moody, A.; Liao, L. H.; Liu, P.; Tomaras, G. D.; Haynes, B. F.; Shen, X.] Duke Univ, Med Ctr, Raleigh, NC USA.
[Zolla-Pazner, S.] NYU, New York, NY USA.
[Bailer, R. T.; Koup, R. A.; Mascola, J. R.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Korber, B. T.] Los Alamos Natl Lab, Santa Fe, NM USA.
[Rerks-Ngarm, S.] MOPH, Bangkok, Thailand.
[Nitayaphan, S.] AFRIMS, Bangkok, Thailand.
[Pitisuttihum, P.; Kaewkungwal, J.] Mahidol Univ, Bangkok 10700, Thailand.
[Mullins, J. I.] Univ Washington, Seattle, WA 98195 USA.
RI Tomaras, Georgia/J-5041-2016
NR 0
TC 2
Z9 2
U1 0
U2 1
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0889-2229
EI 1931-8405
J9 AIDS RES HUM RETROV
JI Aids Res. Hum. Retrovir.
PD NOV 1
PY 2013
VL 29
IS 11
SI SI
BP A168
EP A168
PG 1
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 239PI
UT WOS:000326037500440
ER
PT J
AU Rudicell, RS
Pegu, A
Ko, S
Kwon, Y
Georgiev, I
Wu, X
Zhu, J
Chen, X
Doria-Rose, N
Zhou, T
Yang, Y
Zhang, B
Todd, J
O'Dell, S
Louder, M
Boyington, J
Shi, W
Yang, Z
Haynes, BF
Roederer, M
Rao, S
Kwong, PD
Mascola, JR
Nabel, GJ
AF Rudicell, R. S.
Pegu, A.
Ko, S.
Kwon, Y.
Georgiev, I.
Wu, X.
Zhu, J.
Chen, X.
Doria-Rose, N.
Zhou, T.
Yang, Y.
Zhang, B.
Todd, J.
O'Dell, S.
Louder, M.
Boyington, J.
Shi, W.
Yang, Z.
Haynes, B. F.
Roederer, M.
Rao, S.
Kwong, P. D.
Mascola, J. R.
Nabel, G. J.
TI Engineering a Next Generation VRC01-Like Antibody with Improved In Vitro
and In Vivo Function
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT Conference on AIDS Vaccine
CY OCT 07-10, 2013
CL Barcelona, SPAIN
C1 [Rudicell, R. S.; Pegu, A.; Ko, S.; Kwon, Y.; Georgiev, I.; Chen, X.; Doria-Rose, N.; Zhou, T.; Yang, Y.; Zhang, B.; Todd, J.; O'Dell, S.; Louder, M.; Boyington, J.; Shi, W.; Yang, Z.; Roederer, M.; Rao, S.; Kwong, P. D.; Mascola, J. R.] NIAID, NIH, Bethesda, MD 20892 USA.
[Wu, X.] Rockefeller Univ, New York, NY 10021 USA.
[Zhu, J.] Scripps Res Inst, La Jolla, CA 92037 USA.
[Haynes, B. F.] Duke Univ, Med Ctr, Durham, NC USA.
[Nabel, G. J.] Sanofi, Cambridge, MA USA.
RI Zhou, Tongqing/A-6880-2010
OI Zhou, Tongqing/0000-0002-3935-4637
NR 0
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 2013
VL 29
IS 11
SI SI
BP A48
EP A49
PG 2
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 239PI
UT WOS:000326037500117
ER
PT J
AU Sastry, M
Xu, L
Bhattacharya, S
Nabel, GJ
Bewley, CA
Kwong, PD
AF Sastry, M.
Xu, L.
Bhattacharya, S.
Nabel, G. J.
Bewley, C. A.
Kwong, P. D.
TI Solution Structural Analysis of the Secondary Structure for HIV-1 gp120
Outer Domain by NMR Spectroscopy
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT Conference on AIDS Vaccine
CY OCT 07-10, 2013
CL Barcelona, SPAIN
C1 [Sastry, M.; Xu, L.; Nabel, G. J.; Kwong, P. D.] NIAID, NIH, Bethesda, MD 20892 USA.
[Bhattacharya, S.] New York Struct Biol Ctr, New York, NY USA.
[Bewley, C. A.] NIDDK, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 3
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 2013
VL 29
IS 11
SI SI
BP A27
EP A28
PG 2
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 239PI
UT WOS:000326037500060
ER
PT J
AU Schifanella, L
Gordon, S
Vaccari, M
Binello, N
Caccuri, F
Blackburn, M
Fenizia, C
Doster, M
Pegu, P
Liynage, N
Shen, X
Tomaras, G
Rao, M
Ferrari, G
Venzon, D
Stablien, D
Barnett, S
Tartaglia, J
Franchini, G
AF Schifanella, L.
Gordon, S.
Vaccari, M.
Binello, N.
Caccuri, F.
Blackburn, M.
Fenizia, C.
Doster, M.
Pegu, P.
Liynage, N.
Shen, X.
Tomaras, G.
Rao, M.
Ferrari, G.
Venzon, D.
Stablien, D.
Barnett, S.
Tartaglia, J.
Franchini, G.
TI MF59 and ALUM, in Combination with an ALVAC-SIV/gp120 Vaccine, Induce
Plasmablasts that Differ in the Expression of Homing Markers
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT Conference on AIDS Vaccine
CY OCT 07-10, 2013
CL Barcelona, SPAIN
C1 [Schifanella, L.; Gordon, S.; Vaccari, M.; Binello, N.; Caccuri, F.; Blackburn, M.; Fenizia, C.; Doster, M.; Pegu, P.; Liynage, N.; Venzon, D.; Franchini, G.] NCI, NIH, Bethesda, MD 20892 USA.
[Shen, X.; Tomaras, G.] Duke Human Vaccine Inst, Durham, NC USA.
[Rao, M.] Walter Reed Army Inst Res, US Mil HIV Res Program, Silver Spring, MD USA.
[Ferrari, G.] Duke Univ, Med Ctr, Durham, NC USA.
[Stablien, D.] EMMES Corp, Rockville, MD USA.
[Barnett, S.] Novartis Vaccines & Diagnost Inc, Cambridge, MA USA.
[Tartaglia, J.] Sanofi Pasteur, Swiftwater, PA USA.
RI Tomaras, Georgia/J-5041-2016
NR 0
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 2013
VL 29
IS 11
SI SI
BP A13
EP A13
PG 1
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 239PI
UT WOS:000326037500026
ER
PT J
AU Schramm, C
Doria-Rose, NA
Gorman, J
Moore, PL
Staupe, RP
Zhang, Z
Yang, Y
Bhiman, J
Georgiev, I
Longo, NL
Pancera, M
Mullikin, JC
Karim, SA
Morris, L
Kwong, PD
Mascola, JR
Shapiro, L
AF Schramm, C.
Doria-Rose, N. A.
Gorman, J.
Moore, P. L.
Staupe, R. P.
Zhang, Z.
Yang, Y.
Bhiman, J.
Georgiev, I.
Longo, N. L.
Pancera, M.
Mullikin, J. C.
Karim, S. A.
Morris, L.
Kwong, P. D.
Mascola, J. R.
Shapiro, L.
TI Long CDR H3 of a Broadly-Neutralizing Antibody Is Present at
Recombination
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT Conference on AIDS Vaccine
CY OCT 07-10, 2013
CL Barcelona, SPAIN
C1 [Schramm, C.; Zhang, Z.; Shapiro, L.] Columbia Univ, New York, NY USA.
[Doria-Rose, N. A.; Gorman, J.; Staupe, R. P.; Yang, Y.; Georgiev, I.; Longo, N. L.; Pancera, M.; Kwong, P. D.; Mascola, J. R.] NIAID, NIH, Bethesda, MD 20892 USA.
[Moore, P. L.; Bhiman, J.; Karim, S. A.; Morris, L.] Natl Hlth Lab Serv, Natl Inst Communicable Dis, Johannesburg, South Africa.
[Mullikin, J. C.] NIH, Bethesda, MD 20892 USA.
NR 0
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 2013
VL 29
IS 11
SI SI
BP A54
EP A54
PG 1
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 239PI
UT WOS:000326037500133
ER
PT J
AU Shen, X
Howington, R
Park, H
Sadagopal, S
Kwa, S
Cope, A
Ding, S
Bolton, D
Roederer, M
Amara, R
Picker, L
Seder, R
McElrath, J
Barnett, S
Shattock, R
Felber, B
Pavlakis, G
Pantaleo, G
Montefiori, D
Tomaras, G
AF Shen, X.
Howington, R.
Park, H.
Sadagopal, S.
Kwa, S.
Cope, A.
Ding, S.
Bolton, D.
Roederer, M.
Amara, R.
Picker, L.
Seder, R.
McElrath, J.
Barnett, S.
Shattock, R.
Felber, B.
Pavlakis, G.
Pantaleo, G.
Montefiori, D.
Tomaras, G.
TI Vaccine Induced Epitope Specific Antibodies to the SIV Envelope Are
Distinct from Those Induced to the HIV-1 Envelope
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT Conference on AIDS Vaccine
CY OCT 07-10, 2013
CL Barcelona, SPAIN
C1 [Shen, X.; Howington, R.; Montefiori, D.; Tomaras, G.] Duke Univ, Durham, NC USA.
[Park, H.; Picker, L.] Oregon Hlth & Sci Univ, Beaverton, OR USA.
[Sadagopal, S.; Amara, R.] Emory Univ, Atlanta, GA 30322 USA.
[Kwa, S.] GeoVax Inc, Smyrna, GA USA.
[Cope, A.; Shattock, R.] Univ London Imperial Coll Sci Technol & Med, London, England.
[Ding, S.] EuroVacc Fdn, Amsterdam, Netherlands.
[Bolton, D.] Walter Reed Army Inst Res, Silver Spring, MD USA.
[Roederer, M.; Seder, R.] NIAID, NIH, Bethesda, MD 20892 USA.
[McElrath, J.] Univ Washington, Seattle, WA 98195 USA.
[Barnett, S.] Novartis Vaccines & Diagnost Inc, Cambridge, MA USA.
[Felber, B.; Pavlakis, G.] NCI, Frederick, MD 21701 USA.
[Pantaleo, G.] Univ Lausanne, Lausanne, Switzerland.
RI Tomaras, Georgia/J-5041-2016; Pantaleo, Giuseppe/K-6163-2016
NR 0
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 2013
VL 29
IS 11
SI SI
BP A10
EP A11
PG 2
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 239PI
UT WOS:000326037500019
ER
PT J
AU Sirivichayakul, S
Buranapraditkun, S
Thantiworasit, P
Rosati, M
Felber, B
Pitakpolrat, P
Korber, B
Ruxrungtham, K
AF Sirivichayakul, S.
Buranapraditkun, S.
Thantiworasit, P.
Rosati, M.
Felber, B.
Pitakpolrat, P.
Korber, B.
Ruxrungtham, K.
TI Env-Specific Immunogenicity of Asian Mosaic HIV-1 Subtype AE/B
gag/pol/env Combination and HIV-1 env Alone DNA Vaccine in BALB/c Mice
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT Conference on AIDS Vaccine
CY OCT 07-10, 2013
CL Barcelona, SPAIN
C1 [Sirivichayakul, S.; Buranapraditkun, S.; Thantiworasit, P.; Pitakpolrat, P.; Ruxrungtham, K.] Chulalongkorn Univ, Bangkok, Thailand.
[Rosati, M.; Felber, B.] NIH, Bethesda, MD 20892 USA.
[Korber, B.] LANL, Los Alamos, NM USA.
NR 0
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 2013
VL 29
IS 11
SI SI
BP A154
EP A154
PG 1
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 239PI
UT WOS:000326037500402
ER
PT J
AU Srivatsan, S
Zhou, T
Zhu, J
Yang, Y
Du, X
Zhang, B
Kwong, PD
AF Srivatsan, S.
Zhou, T.
Zhu, J.
Yang, Y.
Du, X.
Zhang, B.
Kwong, P. D.
TI Characterization of Scaffolded PGT128-Specific V3-Glycopeptides for Use
as HIV-1 Immunogens
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT Conference on AIDS Vaccine
CY OCT 07-10, 2013
CL Barcelona, SPAIN
C1 [Srivatsan, S.; Zhou, T.; Zhu, J.; Yang, Y.; Du, X.; Zhang, B.; Kwong, P. D.] NIAID, NIH, Bethesda, MD 20892 USA.
RI Zhou, Tongqing/A-6880-2010
OI Zhou, Tongqing/0000-0002-3935-4637
NR 0
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 2013
VL 29
IS 11
SI SI
BP A27
EP A27
PG 1
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 239PI
UT WOS:000326037500059
ER
PT J
AU Sunshine, J
Kim, M
Carlson, J
Heckerman, D
Migueles, S
McElrath, J
Mullins, JI
Frahm, N
AF Sunshine, J.
Kim, M.
Carlson, J.
Heckerman, D.
Migueles, S.
McElrath, J.
Mullins, J. I.
Frahm, N.
TI Extensive Yet Ineffective Gag Epitope Variant Recognition Observed in
HIV-Progressors
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT Conference on AIDS Vaccine
CY OCT 07-10, 2013
CL Barcelona, SPAIN
C1 [Sunshine, J.; Kim, M.; Mullins, J. I.] Univ Washington, Seattle, WA 98195 USA.
[Carlson, J.; Heckerman, D.] Microsoft Res, Los Angeles, CA USA.
[Migueles, S.] NIH, Bethesda, MD 20892 USA.
[McElrath, J.; Frahm, N.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
NR 0
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 0889-2229
EI 1931-8405
J9 AIDS RES HUM RETROV
JI Aids Res. Hum. Retrovir.
PD NOV 1
PY 2013
VL 29
IS 11
SI SI
BP A127
EP A127
PG 1
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 239PI
UT WOS:000326037500330
ER
PT J
AU Vaccari, M
Gordon, SN
Doster, M
Liynage, N
Pegu, P
Schifanella, L
Keele, BF
Shen, X
Tomaras, GD
Rao, M
Montefiori, DC
Ferrari, G
Foulds, K
Roederer, M
Venzon, D
Stablein, DM
Kim, JH
Michael, NL
Phogat, S
Barnett, SW
Tartaglia, J
Franchini, G
AF Vaccari, M.
Gordon, S. N.
Doster, M.
Liynage, N.
Pegu, P.
Schifanella, L.
Keele, B. F.
Shen, X.
Tomaras, G. D.
Rao, M.
Montefiori, D. C.
Ferrari, G.
Foulds, K.
Roederer, M.
Venzon, D.
Stablein, D. M.
Kim, J. H.
Michael, N. L.
Phogat, S.
Barnett, S. W.
Tartaglia, J.
Franchini, G.
TI Protection from SIVmac251 Acquisition by an ALVAC/SIV/gp120 Regimen Is
Not Improved by the Increase of Anti-Envelope Antibodies and T Cell
Responses
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT Conference on AIDS Vaccine
CY OCT 07-10, 2013
CL Barcelona, SPAIN
C1 [Vaccari, M.; Gordon, S. N.; Doster, M.; Liynage, N.; Pegu, P.; Schifanella, L.; Venzon, D.; Franchini, G.] NCI, NIH, Bethesda, MD 20892 USA.
[Keele, B. F.] Natl Canc Inst, SAIC Frederick, Frederick, MD USA.
[Shen, X.; Tomaras, G. D.] Duke Human Vaccine Inst, Durham, NC USA.
[Rao, M.] Walter Reed Army Inst Res, US Mil HIV Res Program, Silver Spring, MD USA.
[Montefiori, D. C.; Ferrari, G.] Duke Univ, Med Ctr, Durham, NC USA.
[Foulds, K.; Roederer, M.] NIH, Bethesda, MD 20892 USA.
[Stablein, D. M.] EMMES Corp, Rockville, MD USA.
[Kim, J. H.; Michael, N. L.] Walter Reed Army Inst Res, Silver Spring, MD USA.
[Phogat, S.; Tartaglia, J.] Sanofi Pasteur, Swiftwater, PA USA.
[Barnett, S. W.] Novartis Vaccines & Diagnost, Cambridge, MA USA.
RI Tomaras, Georgia/J-5041-2016
NR 0
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 2013
VL 29
IS 11
SI SI
BP A34
EP A34
PG 1
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 239PI
UT WOS:000326037500078
ER
PT J
AU Virnik, K
Hockenbury, M
Ni, Y
Beren, J
Kulkarni, V
Rosati, M
Alicea, C
Pavlakis, GN
Felber, BK
Berkower, I
AF Virnik, K.
Hockenbury, M.
Ni, Y.
Beren, J.
Kulkarni, V.
Rosati, M.
Alicea, C.
Pavlakis, G. N.
Felber, B. K.
Berkower, I.
TI HIV and SIV Vaccine Antigens Expressed by Live Attenuated Rubella
Vectors Elicit Durable Immunity in Rhesus Macaques
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT Conference on AIDS Vaccine
CY OCT 07-10, 2013
CL Barcelona, SPAIN
C1 [Virnik, K.; Hockenbury, M.; Ni, Y.; Beren, J.; Berkower, I.] FDA, Bethesda, MD USA.
[Kulkarni, V.; Rosati, M.; Alicea, C.; Pavlakis, G. N.; Felber, B. K.] NCI, Frederick, MD 21701 USA.
NR 0
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 2013
VL 29
IS 11
SI SI
BP A36
EP A36
PG 1
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 239PI
UT WOS:000326037500082
ER
PT J
AU Wang, Y
Sundling, C
Dai, K
Wilson, R
O'Dell, S
Zhu, J
Xiao, Y
Mascola, JR
Hedestam, GBK
Wyatt, RT
Li, Y
AF Wang, Y.
Sundling, C.
Dai, K.
Wilson, R.
O'Dell, S.
Zhu, J.
Xiao, Y.
Mascola, J. R.
Hedestam, G. B. Karlsson
Wyatt, R. T.
Li, Y.
TI Vaccine-Elicited B Cell Responses Against the HIV-1 Primary Receptor
Binding Site
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT Conference on AIDS Vaccine
CY OCT 07-10, 2013
CL Barcelona, SPAIN
C1 [Sundling, C.; Hedestam, G. B. Karlsson] Karolinska Inst, Stockholm, Sweden.
[Wang, Y.; Dai, K.; Wilson, R.; Zhu, J.; Wyatt, R. T.; Li, Y.] Scripps Res Inst, La Jolla, CA 92037 USA.
[O'Dell, S.; Mascola, J. R.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Xiao, Y.] NIAID, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 3
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 2013
VL 29
IS 11
SI SI
BP A170
EP A170
PG 1
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 239PI
UT WOS:000326037500444
ER
PT J
AU Wieczorek, L
Krebs, S
Kalyanaraman, V
Whitney, S
Matyas, GR
Rao, M
Alving, CR
Tong, T
Molnar, S
Wesberry, M
Chenine, AL
Tovanabutra, S
Sanders-Buell, E
Slike, B
Alam, S
Liao, H
Haynes, BF
Williams, C
Zolla-Pazner, S
Moscoso, C
Cheng, H
Hoelscher, M
Maboko, L
Michael, N
Robb, ML
VanCott, T
Marovich, M
Polonis, V
AF Wieczorek, L.
Krebs, S.
Kalyanaraman, V.
Whitney, S.
Matyas, G. R.
Rao, M.
Alving, C. R.
Tong, T.
Molnar, S.
Wesberry, M.
Chenine, A. Laurence
Tovanabutra, S.
Sanders-Buell, E.
Slike, B.
Alam, S.
Liao, H.
Haynes, B. F.
Williams, C.
Zolla-Pazner, S.
Moscoso, C.
Cheng, H.
Hoelscher, M.
Maboko, L.
Michael, N.
Robb, M. L.
VanCott, T.
Marovich, M.
Polonis, V.
TI Comparable Antigenicity and Immunogenicity of Multimeric Forms of a
Novel, Acute HIV-1 Subtype C Gp145 Envelope for Clinical Development
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT Conference on AIDS Vaccine
CY OCT 07-10, 2013
CL Barcelona, SPAIN
C1 [Wieczorek, L.; Krebs, S.; Matyas, G. R.; Rao, M.; Alving, C. R.; Tong, T.; Molnar, S.; Wesberry, M.; Chenine, A. Laurence; Tovanabutra, S.; Sanders-Buell, E.; Slike, B.; Michael, N.; Robb, M. L.; Polonis, V.] Walter Reed Army Inst Res, Silver Spring, MD USA.
[Wieczorek, L.; Krebs, S.; Tong, T.; Molnar, S.; Wesberry, M.; Chenine, A. Laurence; Tovanabutra, S.; Sanders-Buell, E.; Slike, B.; Robb, M. L.] Henry M Jackson Fdn, Silver Spring, MD USA.
[Kalyanaraman, V.; Whitney, S.; VanCott, T.] Adv Biosci Labs Inc, Rockville, MD USA.
[Matyas, G. R.; Rao, M.; Alving, C. R.; Michael, N.; Marovich, M.; Polonis, V.] US Mil HIV Res Program, Silver Spring, MD USA.
[Alam, S.; Liao, H.; Haynes, B. F.] Duke Univ, Durham, NC USA.
[Williams, C.; Zolla-Pazner, S.] Vet Affairs New York Harbor Healthcare Syst, New York, NY USA.
[Williams, C.; Zolla-Pazner, S.] NYU, Sch Med, New York, NY USA.
[Moscoso, C.; Cheng, H.] Univ Calif Davis, Davis, CA 95616 USA.
[Hoelscher, M.; Maboko, L.] Mbeya Med Res Project, Munich, Germany.
[Hoelscher, M.; Maboko, L.] Univ Munich, Munich, Germany.
[Marovich, M.] NIH DAIDS, Silver Spring, MD USA.
NR 0
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 0889-2229
EI 1931-8405
J9 AIDS RES HUM RETROV
JI Aids Res. Hum. Retrovir.
PD NOV 1
PY 2013
VL 29
IS 11
SI SI
BP A30
EP A30
PG 1
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 239PI
UT WOS:000326037500066
ER
PT J
AU Williams, WB
Jones, K
Liu, P
Trama, AM
Seaton, K
Moody, MA
Vandergrift, N
Wiehe, K
Liao, H
Montefiori, DC
Ochsenbauer, C
Kappes, J
Hammer, SM
Mascola, J
Koup, R
Corey, L
Nabel, G
Gilbert, P
Morgan, CA
Churchyard, G
Maenza, J
Baden, LR
Keefer, M
Graham, BS
Tomaras, GD
Haynes, BF
AF Williams, W. B.
Jones, K.
Liu, P.
Trama, A. M.
Seaton, K.
Moody, M. A.
Vandergrift, N.
Wiehe, K.
Liao, H.
Montefiori, D. C.
Ochsenbauer, C.
Kappes, J.
Hammer, S. M.
Mascola, J.
Koup, R.
Corey, L.
Nabel, G.
Gilbert, P.
Morgan, C. A.
Churchyard, G.
Maenza, J.
Baden, L. R.
Keefer, M.
Graham, B. S.
Tomaras, G. D.
Haynes, B. F.
TI Antibody Repertoire Induced by the Multiclade (Env A, B, C) HIV-1 DNA
Prime, rAd5 Boost VRC Vaccine
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT Conference on AIDS Vaccine
CY OCT 07-10, 2013
CL Barcelona, SPAIN
C1 [Williams, W. B.; Jones, K.; Liu, P.; Trama, A. M.; Seaton, K.; Moody, M. A.; Vandergrift, N.; Wiehe, K.; Liao, H.; Montefiori, D. C.; Tomaras, G. D.; Haynes, B. F.] Duke Univ, Med Ctr, Durham, NC USA.
[Ochsenbauer, C.; Kappes, J.] Univ Alabama Birmingham, Birmingham, AL USA.
[Hammer, S. M.] Columbia Univ, Med Ctr, New York, NY USA.
[Mascola, J.; Koup, R.; Nabel, G.; Graham, B. S.] NIAID, NIH, Bethesda, MD 20892 USA.
[Corey, L.; Maenza, J.] Univ Washington, Seattle, WA 98195 USA.
[Gilbert, P.; Morgan, C. A.] Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA.
[Churchyard, G.] Aurum Inst, Johannesburg, South Africa.
[Baden, L. R.] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Keefer, M.] Univ Rochester, Med Ctr, Rochester, NY 14642 USA.
RI Tomaras, Georgia/J-5041-2016
NR 0
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 0889-2229
EI 1931-8405
J9 AIDS RES HUM RETROV
JI Aids Res. Hum. Retrovir.
PD NOV 1
PY 2013
VL 29
IS 11
SI SI
BP A9
EP A9
PG 1
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 239PI
UT WOS:000326037500015
ER
PT J
AU Yang, Y
Kwong, PD
AF Yang, Y.
Kwong, P. D.
TI Microplate-Formatted Mammalian Protein Expression for Dissection and
Improvement of Antibodies and Immunogens
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT Conference on AIDS Vaccine
CY OCT 07-10, 2013
CL Barcelona, SPAIN
C1 [Yang, Y.; Kwong, P. D.] NIAID, NIH, Bethesda, MD 20892 USA.
NR 0
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 2013
VL 29
IS 11
SI SI
BP A43
EP A43
PG 1
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 239PI
UT WOS:000326037500103
ER
PT J
AU Zhang, B
Kwon, Y
Rudicell, RS
McKee, K
Zhang, Z
Wu, X
Mullikin, JC
Shapiro, L
Mascola, JR
Kwong, PD
AF Zhang, B.
Kwon, Y.
Rudicell, R. S.
McKee, K.
Zhang, Z.
Wu, X.
Mullikin, J. C.
Shapiro, L.
Mascola, J. R.
Kwong, P. D.
CA NISC Comparative Sequencing
TI Improving HIV-1-Neutralizing Antibodies Through Use of Somatic Variants
Identified by Next Generation Sequencing
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT Conference on AIDS Vaccine
CY OCT 07-10, 2013
CL Barcelona, SPAIN
C1 [Zhang, B.; Kwon, Y.; Rudicell, R. S.; McKee, K.; Wu, X.; Mullikin, J. C.; Mascola, J. R.; Kwong, P. D.] NIH, Bethesda, MD 20892 USA.
[Zhang, Z.; NISC Comparative Sequencing] Columbia Univ, New York, NY USA.
RI Kwon, Young Do/A-6957-2010
NR 0
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 2013
VL 29
IS 11
SI SI
BP A45
EP A45
PG 1
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 239PI
UT WOS:000326037500108
ER
PT J
AU Zhou, T
Chen, L
Lynch, R
Wu, X
Srivatsan, S
Moquin, S
Yang, Y
Zhang, B
Mascola, JR
Kwong, PD
AF Zhou, T.
Chen, L.
Lynch, R.
Wu, X.
Srivatsan, S.
Moquin, S.
Yang, Y.
Zhang, B.
Mascola, J. R.
Kwong, P. D.
TI Modalities of Broad and Potent Antibody Neutralization at the
CD4-Binding Site on HIV-1 gp120
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT Conference on AIDS Vaccine
CY OCT 07-10, 2013
CL Barcelona, SPAIN
C1 [Zhou, T.; Chen, L.; Lynch, R.; Wu, X.; Srivatsan, S.; Moquin, S.; Yang, Y.; Zhang, B.; Mascola, J. R.; Kwong, P. D.] NIAID, NIH, Bethesda, MD 20892 USA.
RI Zhou, Tongqing/A-6880-2010
OI Zhou, Tongqing/0000-0002-3935-4637
NR 0
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 2013
VL 29
IS 11
SI SI
BP A41
EP A41
PG 1
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 239PI
UT WOS:000326037500097
ER
PT J
AU Zinszner, H
Voronin, Y
Allen, M
Busch, M
Fruth, U
Golding, H
Khurana, S
Mulenga, J
Peel, S
Schito, M
Fast, P
AF Zinszner, H.
Voronin, Y.
Allen, M.
Busch, M.
Fruth, U.
Golding, H.
Khurana, S.
Mulenga, J.
Peel, S.
Schito, M.
Fast, P.
TI Vaccine-Induced Antibodies: Impact for HIV Diagnosis, Clinical Trial
Participants and Public Health
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Meeting Abstract
CT Conference on AIDS Vaccine
CY OCT 07-10, 2013
CL Barcelona, SPAIN
C1 [Zinszner, H.; Voronin, Y.] Global HIV Vaccine Enterprise, New York, NY USA.
[Allen, M.] NIAID, NIH, Bethesda, MD 20892 USA.
[Busch, M.] Blood Syst Res Inst, San Francisco, CA USA.
[Fruth, U.] WHO, CH-1211 Geneva, Switzerland.
[Golding, H.; Khurana, S.] US FDA, Bethesda, MD 20014 USA.
[Mulenga, J.] Natl Blood Transfus Serv, Lusaka, Zambia.
[Peel, S.; Schito, M.] US MHRP, Bethesda, MD USA.
[Fast, P.] IAVI, New York, NY USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
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 2013
VL 29
IS 11
SI SI
BP A182
EP A182
PG 1
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 239PI
UT WOS:000326037500476
ER
PT J
AU Gurvich, EM
Kenna, GA
Leggio, L
AF Gurvich, Eugenia M.
Kenna, George A.
Leggio, Lorenzo
TI Use of Novel Technology-Based Techniques to Improve Alcohol-Related
Outcomes in Clinical Trials
SO ALCOHOL AND ALCOHOLISM
LA English
DT Review
ID INTERACTIVE VOICE RESPONSE; ECOLOGICAL MOMENTARY ASSESSMENT; TIMELINE
FOLLOW-BACK; MEDICATION COMPLIANCE; ANTIRETROVIRAL THERAPY;
CONTINGENCY-MANAGEMENT; MONITORING-SYSTEM; DRINKING BEHAVIOR; ASSESSMENT
EMA; ADHERENCE
AB With a better understanding of the biologic basis of alcohol dependence and the considerable financial burden of alcohol abuse and dependence, the number of alcohol-related clinical pharmacotherapy trials has been on the rise. Subsequently, the potential to find efficacious treatments is more promising. Unfortunately, alcohol-related trials face a number of challenges, as a result of the difficulties that arise from traditional and outdated methods to collect data and ensure medication adherence. Novel technology-based assessments, such as ecological momentary assessment, interactive voice response, transdermal sensor and medication-event monitoring system provide a prospective solution-albeit not without possible concerns-to the difficulties faced in alcohol-related clinical trials. Clinical trials are meant to define the efficacy of the treatment and to determine an effective and safe dosage. However, due to lack of adherence a drug could inappropriately or mistakenly be judged as ineffective for treating a specific disorder. The described technologies may be important tools to prevent false negatives in validating drug efficacy, to provide consistency in clinical trials and to improve available data regarding the study of pharmacotherapies for alcohol dependence.
C1 [Gurvich, Eugenia M.] Brown Univ, Sch Engn, Biomed Engn Undergrad Program, Providence, RI 02912 USA.
[Kenna, George A.] Brown Univ, Sch Engn, Ctr Alcohol & Addict Studies, Providence, RI 02912 USA.
[Leggio, Lorenzo] NIAAA, Sect Clin Psychoneuroendocrinol & Neuropsychophar, Lab Clin & Translat Studies, NIH, Bethesda, MD 20892 USA.
[Leggio, Lorenzo] NIDA, Intramural Res Program, NIH, Baltimore, MD USA.
[Leggio, Lorenzo] Brown Univ, Dept Behav & Social Sci, Providence, RI 02912 USA.
RP Leggio, L (reprint author), NIAAA, Sect Clin Psychoneuroendocrinol & Neuropsychophar, 10 Ctr Dr 10CRC 15330 MSC 1108,Room 1-5429, Bethesda, MD 20892 USA.
EM lorenzo.leggio@nih.gov
RI Leggio, Lorenzo/M-2972-2016
FU Division of Intramural Clinical and Biological Research of the National
Institute on Alcohol Abuse and Alcoholism (NIAAA); Intramural Research
Program of the National Institute on Drug Abuse (NIDA)
FX Dr Leggio's research is supported by the Division of Intramural Clinical
and Biological Research of the National Institute on Alcohol Abuse and
Alcoholism (NIAAA) and the Intramural Research Program of the National
Institute on Drug Abuse (NIDA).
NR 78
TC 10
Z9 10
U1 3
U2 16
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0735-0414
EI 1464-3502
J9 ALCOHOL ALCOHOLISM
JI Alcohol Alcohol.
PD NOV-DEC
PY 2013
VL 48
IS 6
BP 712
EP 719
DI 10.1093/alcalc/agt134
PG 8
WC Substance Abuse
SC Substance Abuse
GA 239AJ
UT WOS:000325993500014
PM 23955872
ER
PT J
AU Khan, H
Kalogeropoulos, AP
Georgiopoulou, VV
Newman, AB
Harris, TB
Rodondi, N
Bauer, DC
Kritchevsky, SB
Butler, J
AF Khan, Hassan
Kalogeropoulos, Andreas P.
Georgiopoulou, Vasiliki V.
Newman, Anne B.
Harris, Tamara B.
Rodondi, Nicolas
Bauer, Douglas C.
Kritchevsky, Stephen B.
Butler, Javed
TI Frailty and risk for heart failure in older adults: The health, aging,
and body composition study
SO AMERICAN HEART JOURNAL
LA English
DT Article
ID LOWER-EXTREMITY PERFORMANCE; CARDIOVASCULAR-DISEASE; PHYSICAL FRAILTY;
CONTROLLED TRIAL; EXERCISE; MORTALITY; ASSOCIATION; DISABILITY;
PREDICTION; LEVEL
AB Objective The aim of this study was to assess the association between frailty and risk for heart failure (HF) in older adults.
Background Frailty is common in the elderly and is associated with adverse health outcomes. Impact of frailty on HF risk is not known.
Methods We assessed the association between frailty, using the Health ABC Short Physical Performance Battery (HABC Battery) and the Gill index, and incident HF in 2825 participants aged 70 to 79 years.
Results Mean age of participants was 74 +/- 3 years; 48% were men and 59% were white. During a median follow up of 11.4 (7.1-11.7) years, 466 participants developed HF. Compared to non-frail participants, moderate (HR 1.36, 95% CI 1.08-1.71) and severe frailty (HR 1.88, 95% CI 1.02-3.47) by Gill index was associated with a higher risk for HF. HABC Battery score was linearly associated with HF risk after adjusting for the Health ABC HF Model (HR 1.24, 95% CI 1.13-1.36 per SD decrease in score) and remained significant when controlled for death as a competing risk (HR 1.30; 95% CI 1.00-1.55). Results were comparable across age, sex, and race, and in sub-groups based on diabetes mellitus or cardiovascular disease at baseline. Addition of HABC Battery scores to the Health ABC HF Risk Model improved discrimination (change in C-index, 0.014; 95% CI 0.018-0.010) and appropriately reclassified 13.4% (net-reclassification-improvement 0.073, 95% CI 0.021-0.125; P = .006) of participants (8.3% who developed HF and 5.1% who did not).
Conclusions Frailty is independently associated with risk of HF in older adults.
C1 [Khan, Hassan] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England.
[Kalogeropoulos, Andreas P.; Georgiopoulou, Vasiliki V.; Butler, Javed] Emory Univ, Div Cardiol, Atlanta, GA 30322 USA.
[Newman, Anne B.] Univ Pittsburgh, Dept Epidemiol & Med, Pittsburgh, PA USA.
[Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
[Rodondi, Nicolas] Univ Lausanne Hosp, Dept Ambulatory Care & Community Med, Lausanne, Switzerland.
[Bauer, Douglas C.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA.
[Bauer, Douglas C.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
[Kritchevsky, Stephen B.] Wake Forest Sch Med, Sect Gerontol & Geriatr Med, Winston Salem, NC USA.
RP Butler, J (reprint author), Emory Univ Hosp, 1462 Clifton Rd,Suite 504, Atlanta, GA 30322 USA.
EM javed.butler@emory.edu
RI Kalogeropoulos, Andreas/A-9494-2009; Newman, Anne/C-6408-2013
OI Kalogeropoulos, Andreas/0000-0002-1284-429X; Newman,
Anne/0000-0002-0106-1150
FU Intramural NIH HHS [Z01 AG007390-03]
NR 38
TC 25
Z9 26
U1 0
U2 9
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-8703
EI 1097-5330
J9 AM HEART J
JI Am. Heart J.
PD NOV
PY 2013
VL 166
IS 5
BP 887
EP 894
DI 10.1016/j.ahj.2013.07.032
PG 8
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 242IS
UT WOS:000326233500015
PM 24176445
ER
PT J
AU Sysko, R
Devlin, MJ
Schebendach, J
Tanofsky-Kraff, M
Zimmerli, E
Korner, J
Yanovski, JA
Zitsman, JL
Walsh, BT
AF Sysko, Robyn
Devlin, Michael J.
Schebendach, Janet
Tanofsky-Kraff, Marian
Zimmerli, Ellen
Korner, Judith
Yanovski, Jack A.
Zitsman, Jeffrey L.
Walsh, B. Timothy
TI Hormonal responses and test meal intake among obese teenagers before and
after laparoscopic adjustable gastric banding
SO AMERICAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Article
ID PLASMA GHRELIN; ENERGY-INTAKE; WEIGHT-LOSS; ANOREXIA-NERVOSA; PUBERTAL
CHANGES; ADOLESCENTS; VARIETY; SURGERY; BYPASS; PREDICTORS
AB Background: Relatively little is known about changes in eating behavior or hormonal responses to food after bariatric surgery in adolescents.
Objective: This study compared eating behavior and hormones among adolescents in a bariatric surgery program with those in nonoverweight control adolescents and evaluated changes before and after laparoscopic adjustable gastric banding (LAGB).
Design: Fasting leptin, peptide YY (PYY), and ghrelin concentrations were obtained, and postprandial ghrelin and PYY area under the curve (AUC) were assessed after a single-item breakfast. Intake from an ad libitum lunchtime multi-item meal was measured.
Results: Compared with controls (n = 9), all presurgical candidates (n = 20) had significantly greater fasting leptin, lower fasting ghrelin, and lower AUC ghrelin but similar PYY and AUC PYY. Preoperative candidates did not differ from controls in total energy consumed during the test meal. Postoperatively, among the 11 participants with data both before and after surgery, BMI (in kg/m(2)) decreased by 3.5 (P<0.001), significantly less energy was consumed in the test meal, and a smaller number of foods were selected. AUC ghrelin and PYY did not significantly change before or after LAGB.
Conclusions: Few significant short-term changes were observed in appetitive hormones after LAGB. It is unclear whether objective measures of eating behavior will prove useful in evaluating the impact of bariatric surgery on outcomes. This trial was registered at clinicaltrials. gov as CT00764127.
C1 [Sysko, Robyn; Devlin, Michael J.; Schebendach, Janet; Zimmerli, Ellen; Walsh, B. Timothy] New York State Psychiat Inst & Hosp, Columbia Ctr Eating Disorders, Div Clin Therapeut, New York, NY 10032 USA.
[Sysko, Robyn; Devlin, Michael J.; Schebendach, Janet; Zimmerli, Ellen; Walsh, B. Timothy] Columbia Univ, Coll Phys & Surg, Dept Psychiat, New York, NY USA.
[Tanofsky-Kraff, Marian] Uniformed Serv Univ Hlth Sci, Dept Med & Clin Psychol, Bethesda, MD 20814 USA.
[Tanofsky-Kraff, Marian; Yanovski, Jack A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Dev Endocrinol & Genet, Sect Growth & Obes, Bethesda, MD USA.
[Korner, Judith] Columbia Univ, Dept Med, New York, NY USA.
[Zitsman, Jeffrey L.] Columbia Univ, Med Ctr, Ctr Adolescent Bariatr Surg, Dept Surg,Div Pediat Surg, New York, NY USA.
RP Sysko, R (reprint author), New York State Psychiat Inst & Hosp, Columbia Ctr Eating Disorders, Unit 98, 1051 Riverside Dr, New York, NY 10032 USA.
EM syskor@nyspi.columbia.edu
OI Yanovski, Jack/0000-0001-8542-1637
FU National Institute of Diabetes and Digestive and Kidney Diseases [R21
DK074503, DK088532-01A1]; Intramural Research Program of the NIH
[Z1A-HD-00641]
FX Supported by National Institute of Diabetes and Digestive and Kidney
Diseases grants R21 DK074503 (to BTW) and DK088532-01A1 (to RS); and the
Intramural Research Program of the NIH (Z1A-HD-00641; JAY).
NR 34
TC 6
Z9 6
U1 0
U2 1
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 2013
VL 98
IS 5
BP 1151
EP 1161
DI 10.3945/ajcn.113.061762
PG 11
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 239XJ
UT WOS:000326059000003
PM 23985807
ER
PT J
AU Lam, TK
Freedman, ND
Fan, JH
Qiao, YL
Dawsey, SM
Taylor, PR
Abnet, CC
AF Lam, Tram Kim
Freedman, Neal D.
Fan, Jin-Hu
Qiao, You-Lin
Dawsey, Sanford M.
Taylor, Philip R.
Abnet, Christian C.
TI Prediagnostic plasma vitamin C and risk of gastric adenocarcinoma and
esophageal squamous cell carcinoma in a Chinese population
SO AMERICAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Article
ID HELICOBACTER-PYLORI INFECTION; NUTRITION INTERVENTION TRIAL;
GENERAL-POPULATION; CANCER INCIDENCE; ASCORBIC-ACID; FOLLOW-UP; SERUM
MICRONUTRIENTS; RANDOMIZED-TRIAL; MORTALITY; SUPPLEMENTATION
AB Background: China has some of the highest incidence rates for gastric adenocarcinoma (GA) and esophageal squamous cell carcinoma (ESCC) in the world. Prospective studies suggested that vitamin C may reduce risks; however, associations are unclear because of limited sample size.
Objective: The objective was to examine the relation between prediagnostic plasma vitamin C and the risk of GA and ESCC.
Design: A case-cohort study was used to assess the association between prediagnostic plasma vitamin C and incidence of GA (n = 467) and ESCC (n = 618) in the General Population Nutrition Intervention Trial. With the use of multivariate Cox proportional hazards models, we estimated the HRs and 95% CIs. We also conducted a meta-analysis of the literature up to 1 October 2012 on the relation between circulating vitamin C and gastric cancer incidence. Two cohort studies and the current study were included to assess the body of evidence.
Results: For GA, each 20-mu mol/L increase in plasma vitamin C was associated with a 14% decrease in risk (HR: 0.86; 95% CI: 0.76, 0.96). Compared with individuals with low plasma vitamin C concentrations (<= 28 mu mol/L), those with normal concentrations (>28 mu mol/L) had a 27% reduced risk of GA (HR: 0.73; 95% CI: 0.56, 0.94). No association between vitamin C concentrations and ESCC was seen. Meta-analysis showed that the risk of incident GA among those with the highest concentration of plasma vitamin C was 31% lower (random-effects-pooled-odds ratio 0.69; 95% CI: 0.54, 0.89) than those in the lowest category.
Conclusion: Our data provide evidence that higher circulating vitamin C was associated with a reduced risk of incident GA, but no association was seen for ESCC.
C1 [Lam, Tram Kim; Taylor, Philip R.] NCI, Div Canc Epidemiol & Genet, NIH, Genet Epidemiol Branch, Rockville, MD USA.
[Freedman, Neal D.; Dawsey, Sanford M.; Abnet, Christian C.] NCI, Div Canc Epidemiol & Genet, NIH, Nutr Epidemiol Branch, Rockville, MD USA.
[Lam, Tram Kim] NCI, Div Canc Epidemiol & Genet, NIH, Div Canc Control & Populat Sci,Epidemiol & Genom, Rockville, MD USA.
[Fan, Jin-Hu; Qiao, You-Lin] Chinese Acad Med Sci, Inst Canc, Beijing 100021, Peoples R China.
[Fan, Jin-Hu; Qiao, You-Lin] Peking Union Med Coll, Beijing 100021, Peoples R China.
RP Lam, TK (reprint author), 9609 Med Ctr Dr,4E125, Rockville, MD 20850 USA.
EM lamt@mail.nih.gov; qiaoy@cicams.ac.cn
RI Qiao, You-Lin/B-4139-2012; Abnet, Christian/C-4111-2015; Freedman,
Neal/B-9741-2015
OI Qiao, You-Lin/0000-0001-6380-0871; Abnet, Christian/0000-0002-3008-7843;
Freedman, Neal/0000-0003-0074-1098
FU NIH, National Cancer Institute, Division of Cancer Epidemiology and
Genetics
FX Supported by the Intramural Research Program of the NIH, National Cancer
Institute, Division of Cancer Epidemiology and Genetics.
NR 46
TC 13
Z9 13
U1 0
U2 10
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 2013
VL 98
IS 5
BP 1289
EP 1297
DI 10.3945/ajcn.113.061267
PG 9
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 239XJ
UT WOS:000326059000018
PM 24025629
ER
PT J
AU Turkbey, B
Fotin, SV
Huang, RJ
Yin, Y
Daar, D
Aras, O
Bernardo, M
Garvey, BE
Weaver, J
Haldankar, H
Muradyan, N
Merino, MJ
Pinto, PA
Periaswamy, S
Choyke, PL
AF Turkbey, Baris
Fotin, Sergei V.
Huang, Robert J.
Yin, Yin
Daar, Dagane
Aras, Omer
Bernardo, Marcelino
Garvey, Brian E.
Weaver, Juanita
Haldankar, Hrishikesh
Muradyan, Naira
Merino, Maria J.
Pinto, Peter A.
Periaswamy, Senthil
Choyke, Peter L.
TI Fully Automated Prostate Segmentation on MRI: Comparison With Manual
Segmentation Methods and Specimen Volumes
SO AMERICAN JOURNAL OF ROENTGENOLOGY
LA English
DT Article
DE fully automated segmentation; MRI; prostate; segmentation; volume
ID TRANSRECTAL ULTRASONOGRAPHY; RADICAL PROSTATECTOMY; ANTIGEN DENSITY;
GLAND VOLUME; CANCER; ACCURACY; BIOPSY; IMAGES; ULTRASOUND; PREDICT
AB OBJECTIVE. The objective of our study was to compare calculated prostate volumes derived from tridimensional MR measurements (ellipsoid formula), manual segmentation, and a fully automated segmentation system as validated by actual prostatectomy specimens.
MATERIALS AND METHODS. Ninety-eight consecutive patients (median age, 60.6 years; median prostate-specific antigen [PSA] value, 6.85 ng/mL) underwent triplane T2-weighted MRI on a 3-T magnet with an endorectal coil while undergoing diagnostic workup for prostate cancer. Prostate volume estimates were determined using the formula for ellipsoid volume based on tridimensional measurements, manual segmentation of triplane MRI, and automated segmentation based on normalized gradient fields cross-correlation and graph-search refinement. Estimates of prostate volume based on ellipsoid volume, manual segmentation, and automated segmentation were compared with prostatectomy specimen volumes. Prostate volume estimates were compared using the Pearson correlation coefficient and linear regression analysis. The Dice similarity coefficient was used to quantify spatial agreement between manual segmentation and automated segmentation.
RESULTS. The Pearson correlation coefficient revealed strong positive correlation between prostatectomy specimen volume and prostate volume estimates derived from manual segmentation (R = 0.89-0.91, p < 0.0001) and automated segmentation (R = 0.88-0.91, p < 0.0001). No difference was observed between manual segmentation and automated segmentation. Mean partial and full Dice similarity coefficients of 0.92 and 0.89, respectively, were achieved for axial automated segmentation.
CONCLUSION. Prostate volume estimates obtained with a fully automated 3D segmentation tool based on normalized gradient fields cross-correlation and graph-search refinement can yield highly accurate prostate volume estimates in a clinically relevant time of 10 seconds. This tool will assist in developing a broad range of applications including routine prostate volume estimations, image registration, biopsy guidance, and decision support systems.
C1 [Turkbey, Baris; Huang, Robert J.; Daar, Dagane; Aras, Omer; Bernardo, Marcelino; Garvey, Brian E.; Weaver, Juanita; Choyke, Peter L.] NCI, NIH, Mol Imaging Program, Bethesda, MD 20892 USA.
[Fotin, Sergei V.; Yin, Yin; Haldankar, Hrishikesh; Muradyan, Naira; Periaswamy, Senthil] iCAD Inc, Nashua, NH USA.
[Merino, Maria J.] NCI, NIH, Pathol Lab, Bethesda, MD 20892 USA.
[Pinto, Peter A.] NCI, NIH, Urol Oncol Branch, Bethesda, MD 20892 USA.
RP Choyke, PL (reprint author), NCI, NIH, Mol Imaging Program, 10 Ctr Dr,MSC 1182,Bldg 10,Rm B69, Bethesda, MD 20892 USA.
EM pchoyke@mail.nih.gov
NR 28
TC 4
Z9 4
U1 0
U2 5
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 2013
VL 201
IS 5
BP W720
EP W729
DI 10.2214/AJR.12.9712
PG 10
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 240LO
UT WOS:000326097900009
PM 24147502
ER
PT J
AU Golding, A
Hasni, S
Illei, G
Shevach, EM
AF Golding, Amit
Hasni, Sarfaraz
Illei, Gabor
Shevach, Ethan M.
TI The Percentage of FoxP3+Helios + Treg Cells Correlates Positively With
Disease Activity in Systemic Lupus Erythematosus
SO ARTHRITIS AND RHEUMATISM
LA English
DT Article
ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; REGULATORY T-CELLS; REVISED CRITERIA;
FOXP3 EXPRESSION; DISEASE-ACTIVITY; CLASSIFICATION; PHENOTYPE
AB ObjectiveTo assess the use of Helios in combination with FoxP3 as a superior method for identifying non-cytokine-producing human Treg cells in patients with systemic lupus erythematosus (SLE) and to determine if FoxP3+Helios+ Treg cells are maintained at normal levels in patients with clinically active disease.
MethodsPeripheral blood mononuclear cells (PBMCs) were purified from the blood of healthy volunteer donors and from 52 consecutive patients with SLE of varying clinical activity (Systemic Lupus Erythematosus Disease Activity Index scores of 0, 2-4, and 5). PBMCs (either fresh or after 4 hours of stimulation for cytokine production) were then analyzed by flow cytometry for the expression of cell surface markers (CD4, CD25, CD127, and CD45RA) and transcription factors (FoxP3 and Helios), as well as for the production of cytokines (interleukin-2 and interferon-).
ResultsFoxP3+Helios+ Treg cells were found to be non-cytokine producing in both SLE patients and healthy controls. Patients with clinically active SLE had higher percentages of FoxP3+Helios+ Treg cells than did patients with inactive SLE or healthy controls. When corrected for the total CD4 cell count, the absolute numbers of FoxP3+Helios+ Treg cells in patients with moderately-to-highly active SLE were normal.
ConclusionPrevious reports of a deficiency in Treg cell number or function in SLE are limited by their use of CD25, either alone or in combination with other markers, to identify human Treg cells. Helios in combination with FoxP3 is a superior method for detecting all non-cytokine-producing Treg cells, irrespective of CD25 or CD45RA expression. Using this method, we showed that FoxP3+Helios+ Treg cell numbers are not reduced in patients with clinically active SLE.
C1 [Shevach, Ethan M.] NIAID, NIH, Bethesda, MD 20892 USA.
[Hasni, Sarfaraz] NIAMSD, NIH, Bethesda, MD 20892 USA.
[Illei, Gabor] Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA.
RP Golding, A (reprint author), Univ Maryland, Sch Med, Div Rheumatol & Clin Immunol, 10 South Pine St,MSTF Bldg 8-34, Baltimore, MD 21201 USA.
EM agolding@medicine.umaryland.edu
OI Golding, Amit/0000-0003-3659-6654
FU NIH (Intramural Research Programs of the National Institute of Allergy
and Infectious Diseases); NIH (National Institute of Arthritis and
Musculoskeletal and Skin Diseases); NIH (National Institute of Dental
and Craniofacial Research)
FX Supported by the NIH (Intramural Research Programs of the National
Institute of Allergy and Infectious Diseases, the National Institute of
Arthritis and Musculoskeletal and Skin Diseases, and the National
Institute of Dental and Craniofacial Research).
NR 29
TC 28
Z9 29
U1 2
U2 7
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0004-3591
EI 1529-0131
J9 ARTHRITIS RHEUM-US
JI Arthritis Rheum.
PD NOV
PY 2013
VL 65
IS 11
BP 2898
EP 2906
DI 10.1002/art.38119
PG 9
WC Rheumatology
SC Rheumatology
GA 241AG
UT WOS:000326138200019
PM 23925905
ER
PT J
AU Moran, ME
Hulshoff Pol, H
Gogtay, N
AF Moran, Marcel E.
Hulshoff Pol, Hilleke
Gogtay, Nitin
TI A family affair: brain abnormalities in siblings of patients with
schizophrenia
SO BRAIN
LA English
DT Review
DE schizophrenia; imaging; grey matter; endophenotype
ID CHILDHOOD-ONSET SCHIZOPHRENIA; DIZYGOTIC TWINS DISCORDANT; VOXEL-BASED
MORPHOMETRY; GRAY-MATTER DEFICITS; NONPSYCHOTIC SIBLINGS; HEALTHY
SIBLINGS; UNAFFECTED SIBLINGS; HIPPOCAMPAL VOLUME; WHITE-MATTER;
INTERMEDIATE-PHENOTYPE
AB Schizophrenia is a severe mental disorder that has a strong genetic basis. Converging evidence suggests that schizophrenia is a progressive neurodevelopmental disorder, with earlier onset cases resulting in more profound brain abnormalities. Siblings of patients with schizophrenia provide an invaluable resource for differentiating between trait and state markers, thus highlighting possible endophenotypes for ongoing research. However, findings from sibling studies have not been systematically put together in a coherent story across the broader age span. We review here the cortical grey matter abnormalities in siblings of patients with schizophrenia from childhood to adulthood, by reviewing sibling studies from both childhood-onset schizophrenia, and the more common adult-onset schizophrenia. When reviewed together, studies suggest that siblings of patients with schizophrenia display significant brain abnormalities that highlight both similarities and differences between the adult and childhood populations, with shared developmental risk patterns, and segregating trajectories. Based on current research it appears that the cortical grey matter abnormalities in siblings are likely to be an age-dependent endophenotype, which normalize by the typical age of onset of schizophrenia unless there has been more genetic or symptom burdening. With increased genetic burdening (e.g. discordant twins of patients) the grey matter abnormalities in (twin) siblings are progressive in adulthood. This synthesis of the literature clarifies the importance of brain plasticity in the pathophysiology of the illness, indicating that probands may lack protective factors critical for healthy development.
C1 [Moran, Marcel E.; Gogtay, Nitin] NIMH, Child Psychiat Branch, NIH, Bethesda, MD 20814 USA.
[Hulshoff Pol, Hilleke] Univ Med Ctr Utrecht, Rudolf Magnus Inst Neurosci, Dept Psychiat, Utrecht, Netherlands.
RP Moran, ME (reprint author), NIMH, Child Psychiat Branch Bldg 10,10 Ctr Dr,RM 3N202, Bethesda, MD 20814 USA.
EM marcel.moran@nih.gov
RI Hulshoff Pol, Hilleke/B-4795-2014; Gogtay, Nitin/A-3035-2008
OI Hulshoff Pol, Hilleke/0000-0002-2038-5281;
FU Intramural Research Program (IRP) at the National Institute of Mental
Health in Bethesda, MD
FX The present research was funded by the Intramural Research Program (IRP)
at the National Institute of Mental Health in Bethesda, MD.
NR 87
TC 21
Z9 21
U1 5
U2 25
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0006-8950
EI 1460-2156
J9 BRAIN
JI Brain
PD NOV
PY 2013
VL 136
BP 3215
EP 3226
DI 10.1093/brain/awt116
PN 11
PG 12
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 243BQ
UT WOS:000326291800009
PM 23698280
ER
PT J
AU Gallea, C
Popa, T
Hubsch, C
Valabregue, R
Brochard, V
Kundu, P
Schmitt, B
Bardinet, E
Bertasi, E
Flamand-Roze, C
Alexandre, N
Delmaire, C
Meneret, A
Depienne, C
Poupon, C
Hertz-Pannier, L
Cincotta, M
Vidailhet, M
Lehericy, S
Meunier, S
Roze, E
AF Gallea, Cecile
Popa, Traian
Hubsch, Cecile
Valabregue, Romain
Brochard, Vanessa
Kundu, Prantik
Schmitt, Benoit
Bardinet, Eric
Bertasi, Eric
Flamand-Roze, Constance
Alexandre, Nicolas
Delmaire, Christine
Meneret, Aurelie
Depienne, Christel
Poupon, Cyril
Hertz-Pannier, Lucie
Cincotta, Massimo
Vidailhet, Marie
Lehericy, Stephane
Meunier, Sabine
Roze, Emmanuel
TI RAD51 deficiency disrupts the corticospinal lateralization of motor
control
SO BRAIN
LA English
DT Article
DE motor disorders; genetics; corticospinal pathways; transcallosal
inhibition; movement coordination
ID CONGENITAL MIRROR MOVEMENTS; LINKED KALLMANNS-SYNDROME; TRANSCRANIAL
MAGNETIC STIMULATION; INTERHEMISPHERIC INHIBITION;
GENETIC-HETEROGENEITY; CORTICAL POTENTIALS; CORPUS-CALLOSUM; DCC
MUTATION; CORTEX; PROJECTIONS
AB Mirror movements are involuntary symmetrical movements of one side of the body that mirror voluntary movements of the other side. Congenital mirror movement disorder is a rare condition characterized by mirror movements that persist throughout adulthood in subjects with no other clinical abnormalities. The affected individuals have mirror movements predominating in the muscles that control the fingers and are unable to perform purely unimanual movements. Congenital mirror movement disorder thus provides a unique paradigm for studying the lateralization of motor control. We conducted a multimodal, controlled study of patients with congenital mirror movements associated with RAD51 haploinsufficiency (n = 7, mean age 33.3 +/- 16.8 years) by comparison with age- and gender-matched healthy volunteers (n = 14, mean age 33.9 +/- 16.1 years). We showed that patients with congenital mirror movements induced by RAD51 deficiency had: (i) an abnormal decussation of the corticospinal tract; (ii) abnormal interhemispheric inhibition and bilateral cortical activation of primary motor areas during intended unimanual movements; and (iii) an abnormal involvement of the supplementary motor area during both unimanual and bimanual movements. The lateralization of motor control thus requires a fine interplay between interhemispheric communication and corticospinal wiring. This fine interplay determines: (i) the delivery of appropriate motor plans from the supplementary motor area to the primary motor cortex; (ii) the lateralized activation of the primary motor cortex; and (iii) the unilateral transmission of the motor command to the limb involved in the intended movement. Our results also unveil an unexpected function of RAD51 in corticospinal development of the motor system.
C1 [Gallea, Cecile; Popa, Traian; Valabregue, Romain; Bardinet, Eric; Bertasi, Eric; Alexandre, Nicolas; Lehericy, Stephane] Ctr Neuroimagerie Rech CENIR, Inst Cerveau & Moelle Epiniere ICM, F-75651 Paris 13, France.
[Gallea, Cecile; Popa, Traian; Hubsch, Cecile; Meneret, Aurelie; Depienne, Christel; Vidailhet, Marie; Lehericy, Stephane; Meunier, Sabine; Roze, Emmanuel] Univ Paris 06, CNRS UMR 7225, Ctr Rech, Inserm U975,UMR S975,Inst Cerveau & Moelle Epinie, Paris, France.
[Hubsch, Cecile; Meneret, Aurelie; Vidailhet, Marie; Roze, Emmanuel] Grp Hosp Pitie Salpetriere, AP HP, Dept Neurol, Paris, France.
[Brochard, Vanessa] AP HP, INSERM, Ctr Invest Clin 9503, Paris, France.
[Kundu, Prantik] NIMH, Sect Funct Imaging Methods, NIH, Bethesda, MD 20892 USA.
[Schmitt, Benoit] CEA, I2BM, Lab Imagerie & Spect RMN, Gif Sur Yvette, France.
[Flamand-Roze, Constance] Hop Bicetre, AP HP, Serv Neurol, Paris, France.
[Delmaire, Christine] CHRU Lille, Dept Neuroradiol, F-59037 Lille, France.
[Hertz-Pannier, Lucie] CEA, I2BM, Lab Rech Biomed, Neurospin, Gif Sur Yvette, France.
[Cincotta, Massimo] Azienda Sanitaria Firenze, Unita Operat Neurol, Osped San Giovanni di Dio, I-50124 Florence, Italy.
RP Gallea, C (reprint author), Hop La Pitie Salpetriere, Inst Cerveau & Moelle, Ctr Neuroimagerie Rech CENIR, 47-83 Blvd Hop, F-75651 Paris 13, France.
EM cecile.gallea.icm@gmail.com
RI meunier, sabine/G-7622-2014; Popa, Traian/B-7691-2016
OI meunier, sabine/0000-0002-6167-4602; Popa, Traian/0000-0003-1160-4830
FU Fondation pour la Recherche Medicale (FRM); AP-HP; CNRS from
'COSSEC-INSERM'; IHU-A-ICM [ANR-10-IAIHU-06]; IPSEN
FX The authors would like to thank the Fondation pour la Recherche Medicale
(FRM, grant to C.G., programme 'Espoir de la recherche', financement
'Post-doctorat en France'), AP-HP and CNRS ('Poste d'Accueil' for E.R.,
and funding to E.R. from 'COSSEC-INSERM') for their funding support and
the IHU-A-ICM for their financial contribution and logistic support
('Investissement d'avenir' program, ANR-10-IAIHU-06). This work was also
supported by Djilali Mehri and by an unrestricted grant from IPSEN.
NR 69
TC 17
Z9 17
U1 0
U2 10
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0006-8950
EI 1460-2156
J9 BRAIN
JI Brain
PD NOV
PY 2013
VL 136
BP 3333
EP 3346
DI 10.1093/brain/awt258
PN 11
PG 14
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 243BQ
UT WOS:000326291800017
PM 24056534
ER
PT J
AU Kobrinsky, B
Joseph, SO
Muggia, F
Liebes, L
Beric, A
Malankar, A
Ivy, P
Hochster, H
AF Kobrinsky, B.
Joseph, S. O.
Muggia, F.
Liebes, L.
Beric, A.
Malankar, A.
Ivy, P.
Hochster, H.
TI A phase I and pharmacokinetic study of oxaliplatin and bortezomib:
activity, but dose-limiting neurotoxicity
SO CANCER CHEMOTHERAPY AND PHARMACOLOGY
LA English
DT Article
DE Proteasome inhibitor; Bortezomib; Oxaliplatin; Neurotoxicity; Ataxia;
Sensory neuropathy; Oxaliplatin pharmacokinetics
ID PROTEASOME INHIBITOR BORTEZOMIB; METASTATIC COLORECTAL-CANCER;
PHARMACODYNAMIC END-POINTS; SOLID TUMORS; TRIAL; 5-FLUOROURACIL;
NEUROPATHY
AB The potential synergy of modulating platinum-induced DNA damage by combining the proteasome inhibitor bortezomib with oxaliplatin was studied in patients with solid tumors, with special attention to avoidance of cumulative neurotoxicity (NT).
In a 3 + 3 dose escalation design, patients received bortezomib at 1.0-1.5 mg/m(2) on days 1 and 4 and oxaliplatin at 60-85 mg/m(2) on day 1 of a 14-day cycle. NT assessments were performed at the start of every two cycles. Oxaliplatin pharmacokinetics (PK) were determined pre- and post-bortezomib.
Thirty patients were enrolled with 25 (11 men, 14 women) fully evaluable for NT assessments at cycle 2. The median age was 56 years (range 35-74 years); median number of cycles received 2 (range 1-10). At dose levels 2-5 (B 1.3 mg/m(2)), patients manifested NT grades 3 and 4 at a median 3.4 cycles (range 2-9 cycles): 3 had ataxia (one also with sensory neuropathy or neurogenic hypotension, respectively) and 3 had just sensory neuropathy. A 6th dose-level reducing bortezomib to 1.0 mg/m(2) with oxaliplatin 85 mg/m(2)) was explored and no NT or dose limiting toxicities were noted among 7 evaluable patients (5 receiving two or more cycles). Four patients experienced a partial response-one with platinum-resistant ovarian cancer, another with gastroesophageal cancer, another with ampulla of Vater carcinoma, and a patient with cholangiocarcinoma. PK studies at dose levels 1 and 2 showed greater mean ultrafiltrable platinum when oxaliplatin was dosed after bortezomib.
Bortezomib 1.0 mg/m(2) x 2 every 14 days combines safely with oxaliplatin. At higher doses, cumulative NT (i.e., cerebellar signs and sensory neuropathy) occurs at an accelerated pace perhaps from a PK interaction.
C1 [Kobrinsky, B.; Joseph, S. O.; Muggia, F.; Liebes, L.] NYU, Sch Med, Div Hematol & Oncol, New York, NY 10016 USA.
[Beric, A.] NYU, Sch Med, Dept Neurol, New York, NY 10016 USA.
[Malankar, A.] NYU, Clin Trials Off, Inst Canc, New York, NY 10016 USA.
[Ivy, P.] NCI, Bethesda, MD 20892 USA.
[Hochster, H.] Yale Univ, Sch Med, Div Med Oncol, New Haven, CT USA.
RP Muggia, F (reprint author), NYU, Sch Med, Div Hematol & Oncol, 550 1st Ave,OBV C&D Bldg Rm 556, New York, NY 10016 USA.
EM Franco.Muggia@nyumc.org
OI Beric, Aleksandar/0000-0003-4177-2632; Muggia,
Franco/0000-0003-0703-9146
NR 19
TC 3
Z9 4
U1 2
U2 6
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 2013
VL 72
IS 5
BP 1073
EP 1078
DI 10.1007/s00280-013-2295-6
PG 6
WC Oncology; Pharmacology & Pharmacy
SC Oncology; Pharmacology & Pharmacy
GA 240MJ
UT WOS:000326100400014
PM 24048674
ER
PT J
AU Cho, H
Lee, YS
Kim, J
Chung, JY
Kim, JH
AF Cho, Hanbyoul
Lee, You Sun
Kim, Julie
Chung, Joon-Yong
Kim, Jae-Hoon
TI Overexpression of Glucose Transporter-1 (GLUT-1) Predicts Poor Prognosis
in Epithelial Ovarian Cancer
SO CANCER INVESTIGATION
LA English
DT Article
DE GLUT-1; Ovarian cancer; Microarray; Biomarker; Immunohistochemistry
ID GLUCOSE-TRANSPORTER; EXPRESSION; CARCINOMA; SURVIVAL; ANGIOGENESIS;
CELLS
AB Illumina microarray was used to identify differentially expressed genes in three epithelial ovarian cancer (EOC) cells. To validate themicroarray data, mRNA and protein level of glucose transporter-1 (GLUT-1) was examined. GLUT-1 had an EOC/normal cells ratio of 5.51 based on microarray. Real-time PCR and immunohistochemistry demonstrated that GLUT-1 expression was significantly increased in EOC (p=.029 and p<.001, respectively). On survival analysis, GLUT-1 overexpression (HR= 4.80, p=.027) and lymph nodemetastases (HR= 8.35, p=.016) conferred a significantly worse overall survival. In conclusion, GLUT-1 expression is remarkably upregulated in EOC and predicts a poor overall survival.
C1 [Cho, Hanbyoul; Lee, You Sun; Kim, Julie; Kim, Jae-Hoon] Yonsei Univ, Coll Med, Gangnam Severance Hosp, Dept Obstet & Gynecol, Seoul 135720, South Korea.
[Kim, Julie; Chung, Joon-Yong] NCI, Appl Mol Pathol Lab, Pathol Lab, NIH, Bethesda, MD 20892 USA.
RP Kim, JH (reprint author), Yonsei Univ, Coll Med, Gangnam Severance Hosp, Dept Obstet & Gynecol, 146-92 Dogok Dong, Seoul 135720, South Korea.
EM jaehoonkim@yuhs.ac
OI Chung, Joon-Yong/0000-0001-5041-5982
FU National Research Foundation of Korea (NRF); Ministry of Education,
Science and Technology [2011-0005230, 2011-0010286, 2011-0007146];
Yonsei University College of Medicine [3-2010-0072, 6-2011-0073]
FX This work was supported in part by grants from the Basic Science
Research Program through the National Research Foundation of Korea (NRF)
funded by the Ministry of Education, Science and Technology
(2011-0005230, 2011-0010286, and 2011-0007146) and faculty research
grants from Yonsei University College of Medicine for 2010 and 2011
(3-2010-0072 and 6-2011-0073).
NR 24
TC 15
Z9 15
U1 2
U2 11
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 0735-7907
EI 1532-4192
J9 CANCER INVEST
JI Cancer Invest.
PD NOV
PY 2013
VL 31
IS 9
BP 607
EP 615
DI 10.3109/07357907.2013.849722
PG 9
WC Oncology
SC Oncology
GA 244HC
UT WOS:000326377300007
PM 24164300
ER
PT J
AU Kim, J
Kim, Y
Tae, J
Yeom, M
Moon, B
Huang, XP
Roth, BL
Lee, K
Rhim, H
Choo, IH
Chong, Y
Keum, G
Nam, G
Choo, H
AF Kim, Jeeyeon
Kim, Youngjae
Tae, Jinsung
Yeom, Miyoung
Moon, Bongjin
Huang, Xi-Ping
Roth, Bryan L.
Lee, Kangho
Rhim, Hyewhon
Choo, Il Han
Chong, Youhoon
Keum, Gyochang
Nam, Ghilsoo
Choo, Hyunah
TI Aryl Biphenyl-3-ylmethylpiperazines as 5-HT7 Receptor Antagonists
SO CHEMMEDCHEM
LA English
DT Article
DE antagonists; biaryls; aryl piperazines; receptors; structure-activity
relationships
ID SEROTONIN RECEPTOR; MOLECULAR-CLONING; HIGH-AFFINITY; SPINAL 5-HT7;
LIGANDS; SELECTIVITY; AGONIST; DERIVATIVES; INHIBITION; ACTIVATION
AB The 5-HT7 receptor (5-HT7R) is a promising therapeutic target for the treatment of depression and neuropathic pain. The 5-HT7R antagonist SB-269970 exhibited antidepressant-like activity, whereas systemic administration of the 5-HT7R agonist AS-19 significantly inhibited mechanical hypersensitivity and thermal hyperalgesia. In our efforts to discover selective 5-HT7R antagonists or agonists, aryl biphenyl-3-ylmethylpiperazines were designed, synthesized, and biologically evaluated against the 5-HT7R. Among the synthesized compounds, 1-([2-methoxy-(1,1-biphenyl)-3-yl]methyl)-4-(2-methoxyphenyl)piperazine (28) was the best binder to the 5-HT7R (pK(i)=7.83), and its antagonistic property was confirmed by functional assays. The selectivity profile of compound 28 was also recorded for the 5-HT7R over other serotonin receptor subtypes, such as 5-HT1R, 5-HT2R, 5-HT3R, and 5-HT6R. In a molecular modeling study, the 2-methoxyphenyl moiety attached to the piperazine ring of compound 28 was proposed to be essential for the antagonistic function.
C1 [Kim, Jeeyeon; Kim, Youngjae; Yeom, Miyoung; Keum, Gyochang; Nam, Ghilsoo; Choo, Hyunah] Korea Inst Sci & Technol, Ctr Neuromed, Seoul 136791, South Korea.
[Kim, Jeeyeon; Kim, Youngjae; Tae, Jinsung] Yonsei Univ, Dept Chem, Seoul 120749, South Korea.
[Yeom, Miyoung; Moon, Bongjin] Sogang Univ, Dept Chem, Seoul 121742, South Korea.
[Huang, Xi-Ping; Roth, Bryan L.] Univ N Carolina, Natl Inst Mental Hlth Psychoact Drug Screening Pr, Div Med Chem & Nat Prod, Chapel Hill, NC 27599 USA.
[Huang, Xi-Ping; Roth, Bryan L.] Univ N Carolina, Dept Pharmacol, Sch Med, Chapel Hill, NC 27599 USA.
[Lee, Kangho; Rhim, Hyewhon] Korea Inst Sci & Technol, Ctr Neurosci, Seoul 136791, South Korea.
[Lee, Kangho; Rhim, Hyewhon] Univ Sci & Technol, Dept Neurosci, Taejon 305350, South Korea.
[Choo, Il Han] Chosun Univ, Sch Med, Kwangju 501759, South Korea.
[Chong, Youhoon] Konkuk Univ, Dept Biosci & Biotechnol, Seoul 143701, South Korea.
[Choo, Hyunah] Univ Sci & Technol, Dept Biol Chem, Taejon 305350, South Korea.
RP Nam, G (reprint author), Korea Inst Sci & Technol, Ctr Neuromed, Seongbuk gu, Seoul 136791, South Korea.
EM gsnam@kist.re.kr; hchoo@kist.re.kr
RI Keum, Gyochang/E-7492-2013; Roth, Bryan/F-3928-2010
OI Keum, Gyochang/0000-0001-8767-8022;
FU US National Institute of Mental Health (NIMH) Psychoactive Drug
Screening Program [HHSN-271-2008-00025-C]; National Research Foundation
of Korea (NRF); Korean Ministry of Education, Science and Technology:
the Basic Science Research Program [NRF-2013-R1A1A2A10009907]; Priority
Research Centers Program [2012-0006686]; Korea Institute of Science and
Technology (KIST) Institutional Program [2E23770]
FX Binding affinity data were generously provided by the US National
Institute of Mental Health (NIMH) Psychoactive Drug Screening Program
(contract: HHSN-271-2008-00025-C). This research was supported by two
programs of the National Research Foundation of Korea (NRF) funded by
the Korean Ministry of Education, Science and Technology: the Basic
Science Research Program (NRF-2013-R1A1A2A10009907) and the Priority
Research Centers Program (2012-0006686). Additional funding was provided
by the Korea Institute of Science and Technology (KIST) Institutional
Program (2E23770).
NR 42
TC 4
Z9 4
U1 0
U2 7
PU WILEY-V C H VERLAG GMBH
PI WEINHEIM
PA BOSCHSTRASSE 12, D-69469 WEINHEIM, GERMANY
SN 1860-7179
EI 1860-7187
J9 CHEMMEDCHEM
JI ChemMedChem
PD NOV
PY 2013
VL 8
IS 11
BP 1855
EP 1864
DI 10.1002/cmdc.201300240
PG 10
WC Chemistry, Medicinal; Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 241RP
UT WOS:000326185500016
PM 24039134
ER
PT J
AU Enoch, MA
AF Enoch, Mary-Anne
TI Genetic Influences on the Development of Alcoholism
SO CURRENT PSYCHIATRY REPORTS
LA English
DT Article
DE Alcohol use disorders; ALDH2; ADH1B; GABRA2; GABRG1; AUTS2; SGIP1;
5-HTTLPR; HTR2B; HTR3B; HTR3A; CRHR1; MAOA; CHD13; Childhood trauma;
Gene-environment interactions; Flushing response; Addictions array;
GWAS; Exome sequencing; RNA-Seq; GSA; COGA; NESARC; Pharmacogenetics
ID GENOME-WIDE ASSOCIATION; NATIONAL EPIDEMIOLOGIC SURVEY; MU-OPIOID
RECEPTOR; DRUG-DEPENDENCE; USE DISORDERS; LINKAGE DISEQUILIBRIUM;
METABOLIZING GENES; JEWISH POPULATION; CANDIDATE GENES; FAMILY-HISTORY
AB Alcoholism has a substantial heritability yet the detection of specific genetic influences has largely proved elusive. The strongest findings are with genes encoding alcohol metabolizing enzymes. A few candidate genes such as GABRA2 have shown robust associations with alcoholism. Moreover, it has become apparent that variants in stress-related genes such as CRHR1, may only confer risk in individuals exposed to trauma, particularly in early life. Over the past decade there have been tremendous advances in large scale SNP genotyping technologies allowing for genomewide associations studies (GWAS). As a result, it is now recognized that genetic risk for alcoholism is likely to be due to common variants in very many genes, each of small effect, although rare variants with large effects might also play a role. This has resulted in a paradigm shift away from gene centric studies toward analyses of gene interactions and gene networks within biologically relevant pathways.
C1 [Enoch, Mary-Anne] NIAAA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
[Enoch, Mary-Anne] NIAAA, NIH, DICBR, LNG, Bethesda, MD 20892 USA.
RP Enoch, MA (reprint author), NIAAA, NIH, DICBR, LNG, 5625 Fishers Lane,Room 3S32,MSC 9412, Bethesda, MD 20892 USA.
EM maenoch@niaaa.nih.gov
FU National Institute on Alcohol Abuse and Alcoholism, National Institutes
of Health
FX This work was supported by the Intramural Research Program of the
National Institute on Alcohol Abuse and Alcoholism, National Institutes
of Health.
NR 82
TC 19
Z9 20
U1 10
U2 55
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1523-3812
EI 1535-1645
J9 CURR PSYCHIAT REP
JI Curr. Psychiatry Rep.
PD NOV
PY 2013
VL 15
IS 11
AR 412
DI 10.1007/s11920-013-0412-1
PG 9
WC Psychiatry
SC Psychiatry
GA 241SG
UT WOS:000326187300009
PM 24091936
ER
PT J
AU Hong, CW
Nam, AS
Keller, HR
Ligons, DL
Park, JY
Yoon, HW
Park, JJ
Luckey, MA
Park, JH
AF Hong, Changwan
Nam, Anna S.
Keller, Hilary R.
Ligons, Davinna L.
Park, Joo-Young
Yoon, Hee-Won
Park, Joseph J.
Luckey, Megan A.
Park, Jung-Hyun
TI Interleukin-6 expands homeostatic space for peripheral T cells
SO CYTOKINE
LA English
DT Article
DE Apoptosis; Cytokine; Survival; Proliferation; Thymus
ID MYELIN OLIGODENDROCYTE GLYCOPROTEIN; TRANSGENIC MICE; IN-VIVO;
GROWTH-FACTOR; AUTOIMMUNE ENCEPHALOMYELITIS; IL-6-DEFICIENT MICE;
RECEPTOR EXPRESSION; SIGNAL TRANSDUCER; FAMILY CYTOKINES; UP-REGULATION
AB T cell homeostasis and survival is dependent on interleukin-7 (IL-7). Immune activation, however, downregulates IL-7 receptor expression on T cells so that T cell survival during activation must be maintained independently of IL-7. The pro-inflammatory cytokine IL-6 shares common signaling pathways with IL-7 and can promote T cell survival in vitro. But whether IL-6 promotes T cell survival and homeostasis in vivo is not clear. Notably, IL-6 overexpression results in massive plasmacytosis and autoimmunity so that an IL-6 effect on in vivo T cell survival has remained untested. To overcome this limitation, here we generated IL-6 transgenic mice on an immunoglobulin heavy chain (IgH) deficient background which rendered them B cell deficient. Notably, such IgH(KO)IL6(Tg) mice were free of any signs of inflammation or autoimmunity and remained healthy throughout the course of analysis. In these mice, we found that IL-6 overexpression significantly increased peripheral T cell numbers, but importantly without increasing thymopoiesis. Moreover, IL-6 signaled T cells maintained their naive phenotype and did not express activation/memory markers, suggesting that increased T cell numbers were due to increased T cell survival and not because of expansion of activated T cells. Mechanistically, we found that IL-6 signaling induced expression of pro-survival factors Mcl-1 and Pim-1/-2 but not Bcl-2. Thus, IL-6 is a T cell homeostatic cytokine that expands T cell space and can maintain the naive T cell pool. Published by Elsevier Ltd.
C1 [Hong, Changwan; Nam, Anna S.; Keller, Hilary R.; Ligons, Davinna L.; Park, Joo-Young; Yoon, Hee-Won; Park, Joseph J.; Luckey, Megan A.; Park, Jung-Hyun] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA.
[Nam, Anna S.] Univ Missouri, Sch Med, Columbia, MO 65201 USA.
[Nam, Anna S.] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA.
RP Park, JH (reprint author), NCI, Expt Immunol Branch, NIH, Bldg 10,Room 5B17,10 Ctr Dr, Bethesda, MD 20892 USA.
EM parkhy@mail.nih.gov
RI Park, Jung Hyun /B-5712-2015; Davis, Megan/F-5339-2015;
OI Park, Jung Hyun /0000-0002-9547-9055; Park, Joseph/0000-0003-1311-5416
FU US National Institutes of Health, National Cancer Institute, Center for
Cancer Research
FX We thank Drs. A. Singer and R. Etzensperger for critical review of this
manuscript. We thank Drs. Wayne Chu and Phil Lucas for providing us
reagents and protocol for performing TREC assays. This work was
supported by the Intramural Research Program of the US National
Institutes of Health, National Cancer Institute, Center for Cancer
Research.
NR 65
TC 3
Z9 3
U1 0
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 2013
VL 64
IS 2
BP 532
EP 540
DI 10.1016/j.cyto.2013.08.001
PG 9
WC Biochemistry & Molecular Biology; Cell Biology; Immunology
SC Biochemistry & Molecular Biology; Cell Biology; Immunology
GA 242QT
UT WOS:000326257800010
PM 23988623
ER
PT J
AU Collette, NM
Yee, CS
Murugesh, D
Sebastian, A
Taher, L
Gale, NW
Economides, AN
Harland, RM
Loots, GG
AF Collette, Nicole M.
Yee, Cristal S.
Murugesh, Deepa
Sebastian, Aimy
Taher, Leila
Gale, Nicholas W.
Economides, Aris N.
Harland, Richard M.
Loots, Gabriela G.
TI Sost and its paralog Sostdc1 coordinate digit number in a Gli3-dependent
manner
SO DEVELOPMENTAL BIOLOGY
LA English
DT Article
DE WNT signaling; Sost; Sclerostin; Sostdc1; Shh; Limb formation;
Polydactyly; syndactyly
ID BONE MORPHOGENETIC PROTEIN; BMP ANTAGONIST; POLARIZING ACTIVITY;
TARGETED DELETION; WNT/BETA-CATENIN; SONIC-HEDGEHOG; GENE-1 USAG-1;
PROBE LEVEL; SCLEROSTIN; MOUSE
AB WNT signaling is critical in most aspects of skeletal development and homeostasis, and antagonists of WNT signaling are emerging as key regulatory proteins with great promise as therapeutic agents for bone disorders. Here we show that Sost and its paralog Sostdc1 emerged through ancestral genome duplication and their expression patterns have diverged to delineate non-overlapping domains in most organ systems including musculoskeletal, cardiovascular, nervous, digestive, reproductive and respiratory. In the developing limb, Sost and Sostdc1 display dynamic expression patterns with Sost being restricted to the distal ectoderm and Sostdc1 to the proximal ectoderm and the mesenchyme. While Sostdc1(-/-) mice lack any obvious limb or skeletal defects, Sost(-/-) mice recapitulate the hand defects described for Sclerosteosis patients. However, elevated WNT signaling in Sost(-/-); Sostdc1(-/-) mice causes misregulation of SHH signaling, ectopic activation of Sox9 in the digit 1 field and preaxial polydactyly in a Gli1- and Gli3-dependent manner. In addition, we show that the syndactyly documented in Sclerosteosis is present in both Sost(-/-) and Sost(-/-); Sostdc1(-/-) mice, and is driven by misregulation of Fgf8 in the AER, a region lacking Sost and Sostdc1 expression. This study highlights the complexity of WNT signaling in skeletal biology and disease and emphasizes how redundant mechanism and non-cell autonomous effects can synergize to unveil new intricate phenotypes caused by elevated WNT signaling. (C) 2013 The Authors. Published by Elsevier Inc. All rights reserved.
C1 [Collette, Nicole M.; Yee, Cristal S.; Murugesh, Deepa; Sebastian, Aimy; Loots, Gabriela G.] Lawrence Livermore Natl Lab, Biol & Biotechnol Div, Livermore, CA 94550 USA.
[Yee, Cristal S.; Sebastian, Aimy; Loots, Gabriela G.] Univ Calif, Sch Nat Sci, Merced, CA USA.
[Taher, Leila] NIH, Computat Biol Branch, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA.
[Taher, Leila] Univ Rostock, Inst Biostat & Informat Med & Ageing Res, D-18055 Rostock, Germany.
[Gale, Nicholas W.; Economides, Aris N.] Regeneron Pharmaceut Inc, Tarrytown, NY 10591 USA.
[Harland, Richard M.] Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA.
RP Loots, GG (reprint author), Lawrence Livermore Natl Lab, Biol & Biotechnol Div, 7000 East Ave,L-452, Livermore, CA 94550 USA.
EM loots1@llnl.gov
OI Economides, Aris/0000-0002-6508-8942; Sebastian,
Aimy/0000-0002-7822-7040
FU National Institutes of Health (NIH) Knock-Out Mouse Program (KOMP); NIH
[HD47853, DK075730]; U.S. Department of Energy by Lawrence Livermore
National Laboratory [DE-AC52-07NA27344]; NIH, NLM
FX We would like to thank the National Institutes of Health (NIH) Knock-Out
Mouse Program (KOMP) and Regeneron for providing the Sost and Sostdc1
knockout mice. NMC, CV, DM and GGL were supported by NIH Grant HD47853
and DK075730. This work was performed under the auspices of the U.S.
Department of Energy by Lawrence Livermore National Laboratory under
Contract DE-AC52-07NA27344. LT was supported by the Intramural Research
Program of the NIH, NLM.
NR 72
TC 9
Z9 9
U1 0
U2 7
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0012-1606
EI 1095-564X
J9 DEV BIOL
JI Dev. Biol.
PD NOV 1
PY 2013
VL 383
IS 1
BP 90
EP 105
DI 10.1016/j.ydbio.2013.08.015
PG 16
WC Developmental Biology
SC Developmental Biology
GA 239WX
UT WOS:000326057800011
PM 23994639
ER
PT J
AU Werner, JM
Abdalla, A
Gara, N
Ghany, MG
Rehermann, B
AF Werner, Jens M.
Abdalla, Adil
Gara, Naveen
Ghany, Marc G.
Rehermann, Barbara
TI The Hepatitis B Vaccine Protects Re-Exposed Health Care Workers, But
Does Not Provide Sterilizing Immunity
SO GASTROENTEROLOGY
LA English
DT Article
DE Immunization; Immune Response; T Cell; Virus
ID SURFACE-ANTIGEN; RESPONSES; ANTIBODY; BOOSTER; IMMUNOGENICITY; RECOVERY;
EFFICACY; DECADES
AB BACKGROUND & AIMS: Infection with hepatitis B virus (HBV) can be prevented by vaccination with HB surface (HBs) antigen, which induces HBs-specific antibodies and T cells. However, the duration of vaccine-induced protective immunity is poorly defined for health care workers who were vaccinated as adults. METHODS: We investigated the immune mechanisms (antibody and T-cell responses) of long-term protection by the HBV vaccine in 90 health care workers with or without occupational exposure to HBV, 10-28 years after vaccination. RESULTS: Fifty-nine of 90 health care workers (65%) had levels of antibodies to HBs antigen above the cut-off (> 12 mIU/mL) and 30 of 90 (33%) had HBs-specific T cells that produced interferon-gamma. Titers of antibodies to HBs antigen correlated with numbers of HBs-specific interferon-gamma-producing T cells, but not with time after vaccination. Although occupational exposure to HBV after vaccination did not induce antibodies to the HBV core protein (HBcore), the standard biomarker for HBV infection, CD4(+) and CD8(+) T cells against HBcore and polymerase antigens were detected. Similar numbers of HBcore- and polymerase-specific CD4(+) and CD8(+) T cells were detected in health care workers with occupational exposure to HBV and in patients who acquired immunity via HBV infection. Most of the HBcore- and polymerase-specific T cells were CD45RO(+) CCR7(-)CD127(-) effector memory cells in exposed health care workers and in patients with acquired immunity. In contrast, most of the vaccine-induced HBs-specific T cells were CD45RO(-)CCR7(-)CD127(-) terminally differentiated cells. CONCLUSIONS: HBs antigen vaccine-induced immunity protects against future infection but does not provide sterilizing immunity, as evidenced by HBcore- and polymerase-specific CD8(+) T cells in vaccinated health care workers with occupational exposure to HBV. The presence of HBcore- and HBV polymerase-specific T-cell responses is a more sensitive indicator of HBV exposure than detection of HBcore-specific antibodies.
C1 [Werner, Jens M.; Rehermann, Barbara] NIDDK, Immunol Sect, NIH, US Dept HHS, Bethesda, MD 20892 USA.
[Werner, Jens M.; Abdalla, Adil; Gara, Naveen; Ghany, Marc G.; Rehermann, Barbara] NIDDK, Liver Dis Branch, NIH, US Dept HHS, Bethesda, MD 20892 USA.
RP Rehermann, B (reprint author), NIDDK, Immunol Sect, Liver Dis Branch, NIH,US Dept HHS, 10 Ctr Dr,Bldg 10,Room 9B16, Bethesda, MD 20892 USA.
EM Rehermann@nih.gov
OI Werner, Jens/0000-0001-7156-4370
FU National Institute of Diabetes and Digestive and Kidney Diseases,
National Institutes of Health intramural research program; Deutsche
Forschungsgemeinschaft (DFG), Bonn, Germany [We-4675/1-1]
FX This study was supported by the National Institute of Diabetes and
Digestive and Kidney Diseases, National Institutes of Health intramural
research program. JMW was supported by grant We-4675/1-1 from the
Deutsche Forschungsgemeinschaft (DFG), Bonn, Germany.
NR 21
TC 15
Z9 16
U1 0
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 0016-5085
EI 1528-0012
J9 GASTROENTEROLOGY
JI Gastroenterology
PD NOV
PY 2013
VL 145
IS 5
BP 1026
EP 1034
DI 10.1053/j.gastro.2013.07.044
PG 9
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 238UV
UT WOS:000325977600029
PM 23916846
ER
PT J
AU McDonald, CL
AF McDonald, Cheryl L.
TI Dr. Sonia Skarlatos and the National Heart, Lung, and Blood Institute
Translational Research and Resource Programs
SO HUMAN GENE THERAPY
LA English
DT Review
ID LEFT-VENTRICULAR FUNCTION; CELL THERAPY RESEARCH; ACUTE
MYOCARDIAL-INFARCTION; MARROW MONONUCLEAR-CELLS; RESEARCH NETWORK CCTRN;
GENE-THERAPY; RANDOMIZED-TRIAL; DELIVERY; DISEASES; NHLBI
AB Sonia I. Skarlatos, PhD (September 28, 1953-August 6, 2013), was the deputy director of the Division of Cardiovascular Sciences at the National Heart, Lung, and Blood Institute (NHLBI). This article reviews her work in establishing, leading, or facilitating extramural translational research programs supported by the NHLBI, specifically focusing on her work as a consistent advocate for the advancement of gene and cell therapies.
C1 [McDonald, Cheryl L.] NHLBI, Div Cardiovasc Sci, NIH, Bethesda, MD 20892 USA.
RP McDonald, CL (reprint author), 6701 Rockledge Dr Room 8114,MSC 7940, Bethesda, MD 20892 USA.
EM mcdonalc@nhlbi.nih.gov
NR 17
TC 1
Z9 1
U1 0
U2 0
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1043-0342
EI 1557-7422
J9 HUM GENE THER
JI Hum. Gene Ther.
PD NOV 1
PY 2013
VL 24
IS 11
BP 899
EP 905
DI 10.1089/hum.2013.2511
PG 7
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 241QZ
UT WOS:000326183700003
PM 24164237
ER
PT J
AU Grassi, MFR
Olavarria, VN
Kruschewsky, RD
Yamano, Y
Jacobson, S
Taylor, GP
Martin, F
Galvao-Castro, B
AF Rios Grassi, Maria Fernanda
Olavarria, Viviana Nilla
Kruschewsky, Ramon de Almeida
Yamano, Yoshihisa
Jacobson, Steven
Taylor, Graham P.
Martin, Fabiola
Galvao-Castro, Bernardo
TI Utility of HTLV proviral load quantification in diagnosis of
HTLV-1-associated myelopathy requires international standardization
SO JOURNAL OF CLINICAL VIROLOGY
LA English
DT Article
DE HTLV-1; Proviral load; HAM/TSP; Cut-off value; Diagnosis
ID LYMPHOTROPIC VIRUS TYPE-1; SPASTIC PARAPARESIS HAM/TSP; VIRAL LOAD;
ASYMPTOMATIC CARRIERS; PERIPHERAL-BLOOD; INFECTION; CRITERIA; DISEASE;
MARKER; ASSAYS
C1 [Rios Grassi, Maria Fernanda; Galvao-Castro, Bernardo] Fundacao Oswaldo Cruz, Goncalo Moniz Ctr, Adv Lab Publ Hlth, Salvador, BA, Brazil.
[Rios Grassi, Maria Fernanda; Olavarria, Viviana Nilla; Kruschewsky, Ramon de Almeida; Galvao-Castro, Bernardo] Bahiana Sch Med & Publ Hlth EBMSP, Salvador, BA, Brazil.
[Yamano, Yoshihisa] St Marianna Univ, Sch Med, Inst Med Sci, Dept Rare Dis Res, Kawasaki, Kanagawa, Japan.
[Jacobson, Steven] NINDS, Viral Immunol Sect, NIH, Bethesda, MD 20892 USA.
[Taylor, Graham P.] Univ London Imperial Coll Sci Technol & Med, Fac Med, Infect Dis Sect, London, England.
[Martin, Fabiola] Univ York, Hull & York Med Sch, Dept Biol, Ctr Immunol & Infect, York YO10 5DD, N Yorkshire, England.
RP Grassi, MFR (reprint author), Fundacao Oswaldo Cruz Bahia FIOCRUZ, Goncalo Moniz Ctr, Adv Lab Publ Hlth, Rua Waldemar Falcao 121, BR-40296710 Salvador, BA, Brazil.
EM grassi@bahia.fiocruz.br; vini_olavarria@hotmail.com;
ramonkruschewsky@bahiana.edu.br; yyamano@marianna-u.ac.jp;
jacobsons@ninds.nih.gov; g.p.taylor@imperial.ac.uk;
fabiola.martin@hyms.ac.uk; bgalvao@bahiana.edu.br
FU Fundacao de Amparo a Pesquisa da Bahia (FAPESB)
FX Fundacao de Amparo a Pesquisa da Bahia (FAPESB).
NR 17
TC 1
Z9 1
U1 0
U2 3
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1386-6532
EI 1873-5967
J9 J CLIN VIROL
JI J. Clin. Virol.
PD NOV
PY 2013
VL 58
IS 3
BP 584
EP 586
DI 10.1016/j.jcv.2013.09.003
PG 3
WC Virology
SC Virology
GA 241OK
UT WOS:000326176400017
PM 24095029
ER
PT J
AU Acquavella, N
Fojo, T
AF Acquavella, Nicolas
Fojo, Tito
TI Renal Cell Carcinoma: Trying but Failing to Improve the Only Curative
Therapy
SO JOURNAL OF IMMUNOTHERAPY
LA English
DT Editorial Material
ID PHASE-III TRIAL; RECOMBINANT INTERLEUKIN-2 THERAPY; ENDOTHELIAL
GROWTH-FACTOR; HIGH-DOSE INTERLEUKIN-2; METASTATIC MELANOMA; ADOPTIVE
IMMUNOTHERAPY; COMPLETE RESPONSES; INTERFERON-ALPHA; DOUBLE-BLIND;
CANCER
C1 [Acquavella, Nicolas; Fojo, Tito] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Fojo, T (reprint author), NCI, Ctr Canc Res, NIH, Bldg 10,Room 12N226,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM acquavellapesn@mail.nih.gov; fojot@mail.nih.gov
NR 38
TC 1
Z9 1
U1 0
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1524-9557
EI 1537-4513
J9 J IMMUNOTHER
JI J. Immunother.
PD NOV-DEC
PY 2013
VL 36
IS 9
BP 459
EP 461
DI 10.1097/CJI.0000000000000002
PG 3
WC Oncology; Immunology; Medicine, Research & Experimental
SC Oncology; Immunology; Research & Experimental Medicine
GA 242WH
UT WOS:000326275000001
PM 24145356
ER
PT J
AU Mazzetto-Betti, KC
Leoni, RF
Pontes-Neto, OM
Sturzbecher, MJ
Santos, AC
Leite, JP
Silva, AC
de Araujo, DB
AF Mazzetto-Betti, Kelley C.
Leoni, Renata F.
Pontes-Neto, Octavio M.
Sturzbecher, Marcio J.
Santos, Antonio C.
Leite, Joao P.
Silva, Afonso C.
de Araujo, Draulio B.
TI Quantification of BOLD fMRI Parameters to Infer Cerebrovascular
Reactivity of the Middle Cerebral Artery
SO JOURNAL OF MAGNETIC RESONANCE IMAGING
LA English
DT Article
DE BOLD; fMRI; hypercapnia; cerebrovascular reactivity; auditory stimulus;
middle cerebral artery
ID LEVEL-DEPENDENT MRI; FUNCTIONAL MRI; BLOOD-FLOW; HYPERCAPNIA; BRAIN;
REPRODUCIBILITY; STIMULATION; DISEASE; STROKE; MODEL
AB PurposeTo quantify the amplitude and temporal aspects of the blood oxygenation level-dependent (BOLD) response to an auditory stimulus during normocapnia and hypercapnia in healthy subjects in order to establish which BOLD parameters are best suited to infer the cerebrovascular reactivity (CVR) in the middle cerebral artery (MCA) territory.
Materials and MethodsTwenty healthy volunteers (mean age: 23.6 3.7 years, 11 women) were subjected to a functional paradigm composed of five epochs of auditory stimulus (3 sec) intercalated by six intervals of rest (21 sec). Two levels of hypercapnia were achieved by a combination of air and CO2 while the end-tidal CO2 (ETCO2) was continually measured. An autoregressive method was applied to analyze four parameters of the BOLD signal: onset-time, time-to-peak, full-width-at-half-maximum (FWHM), and amplitude.
ResultsBOLD onset time (P < 0.001) and full-width at half-maximum (FWHM) (P < 0.05) increased linearly, while BOLD amplitude decreased (P < 0.001) linearly with increasing levels of hypercapnia. Test-retest for reproducibility in five subjects revealed excellent concordance for onset time and amplitude.
ConclusionThe robust linear dependence of BOLD onset time, FWHM, and amplitude to hypercapnia suggest future application of this protocol in clinical studies aimed at evaluating CVR of the MCA territory. J. Magn. Reson. Imaging 2013;38:1203-1209. (c) 2012 Wiley Periodicals, Inc.
C1 [Mazzetto-Betti, Kelley C.; Leoni, Renata F.; Pontes-Neto, Octavio M.; Sturzbecher, Marcio J.; Santos, Antonio C.; Leite, Joao P.; de Araujo, Draulio B.] Univ Sao Paulo, Dept Neurosci & Behav Sci, FMRP, BR-14049 Ribeirao Preto, Brazil.
[Leoni, Renata F.; Silva, Afonso C.] NINDS, Cerebral Microcirculat Unit, Lab Funct & Mol Imaging, NIH, Bethesda, MD 20892 USA.
[Sturzbecher, Marcio J.; de Araujo, Draulio B.] Univ Sao Paulo, Dept Phys, FFCLRP, BR-14049 Ribeirao Preto, Brazil.
[de Araujo, Draulio B.] Univ Fed Rio Grande do Norte, Onofre Lopes Univ Hosp, BR-59072970 Natal, RN, Brazil.
[de Araujo, Draulio B.] Univ Fed Rio Grande do Norte, Inst Brain, BR-59072970 Natal, RN, Brazil.
RP de Araujo, DB (reprint author), Univ Fed Rio Grande do Norte, Inst Brain, R Nascimento Castro 2155, BR-59056450 Natal, RN, Brazil.
EM draulio@neuro.ufrn.br
RI Leite, Joao/B-9070-2012; Pontes-Neto, Octavio/G-4294-2012; Araujo,
Draulio/I-6038-2012;
OI Leite, Joao/0000-0003-0558-3519; Pontes-Neto,
Octavio/0000-0003-0317-843X; Araujo, Draulio/0000-0002-6934-2485; Leoni,
Renata/0000-0002-4568-0746
FU FAPESP [2009/08691-7]; NIH; CNPq; CAPES; NINDS
FX Contract grant sponsor: FAPESP; Contract grant number: 2009/08691-7;
Contract grant sponsor: Intramural Research Program of the NIH, NINDS
(Alan P. Koretsky, Scientific Director), CNPq and CAPES.
NR 20
TC 0
Z9 0
U1 0
U2 8
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1053-1807
EI 1522-2586
J9 J MAGN RESON IMAGING
JI J. Magn. Reson. Imaging
PD NOV
PY 2013
VL 38
IS 5
BP 1203
EP 1209
DI 10.1002/jmri.23943
PG 7
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 241DP
UT WOS:000326146900025
PM 23188762
ER
PT J
AU Shah, S
Lie, RK
AF Shah, Seema
Lie, Reidar K.
TI Aiming at a moving target: research ethics in the context of evolving
standards of care and prevention
SO JOURNAL OF MEDICAL ETHICS
LA English
DT Article
DE Ethics Committees; Consultation; Research Ethics; Applied and
Professional Ethics; Codes of; Position Statements on Professional
Ethics; HIV Infection and AIDS
ID INTERNATIONAL CONSENSUS OPINION; PRACTICE GUIDELINES; CLINICAL-TRIALS;
THERAPY; DEBATE
AB In rapidly evolving medical fields where the standard of care or prevention changes frequently, guidelines are increasingly likely to conflict with what participants receive in research. Although guidelines typically set the standard of care, there are some cases in which research can justifiably deviate from guidelines. When guidelines conflict with research, an ethical issue only arises if guidelines are rigorous and should be followed. Next, it is important that the cumulative evidence and the conclusions reached by the guidelines do not eliminate the need for further research. Even when guidelines are rigorous and the study still asks an important question, we argue that there may be good reasons for deviations in three cases: (1) when research poses no greater net risk than the standard of care; (2) when there is a continued need for additional evidence, for example, when subpopulations are not covered by the guidelines; and (3) less frequently, when clinical practice guidelines can be justified by the evidence, but practitioners disagree about the guidelines, and the guidelines are not consistently followed as a result. We suggest that procedural protections may be especially useful in deciding when studies in the third category can proceed.
C1 [Shah, Seema] NIH, Dept Bioeth, Ctr Clin, Bethesda, MD 20892 USA.
[Lie, Reidar K.] Univ Bergen, Dept Philosophy, Bergen, Norway.
RP Shah, S (reprint author), NIH, Dept Bioeth, 10 Ctr Dr,Bldg 10,Rm 1C118, Bethesda, MD 20892 USA.
EM shahse@mail.nih.gov
FU NIH Clinical Center; Division of AIDS at the National Institute of
Allergy and Infectious Diseases
FX This research was supported by the Intramural Research Program of the
NIH Clinical Center and by the Division of AIDS at the National
Institute of Allergy and Infectious Diseases.
NR 23
TC 1
Z9 1
U1 1
U2 9
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0306-6800
EI 1473-4257
J9 J MED ETHICS
JI J. Med. Ethics
PD NOV
PY 2013
VL 39
IS 11
BP 699
EP 702
DI 10.1136/medethics-2012-100502
PG 4
WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical
SC Social Sciences - Other Topics; Medical Ethics; Social Issues;
Biomedical Social Sciences
GA 240HX
UT WOS:000326087200011
PM 23322683
ER
PT J
AU Brim, RL
Miller, FG
AF Brim, Remy L.
Miller, Franklin G.
TI The potential benefit of the placebo effect in sham-controlled trials:
implications for risk-benefit assessments and informed consent
SO JOURNAL OF MEDICAL ETHICS
LA English
DT Article
DE Research Ethics; Policy Guidelines; Inst; Review Boards; Review Cttes;
Informed Consent
ID PARKINSONS-DISEASE; DOPAMINE RELEASE; CLINICAL-TRIALS; SURGERY;
EXPECTATION; ETHICS; PAIN; ACUPUNCTURE; ANALGESIA; OUTCOMES
AB There has been considerable debate surrounding the ethics of sham-controlled trials of procedures and interventions. Critics argue that these trials are unethical because participants assigned to the control group have no prospect of benefit from the trial, yet they are exposed to all the risks of the sham intervention. However, the placebo effect associated with sham procedures can often be substantial and has been well documented in the scientific literature. We argue that, in light of the scientific evidence supporting the benefits of sham interventions for pain and Parkinson's disease that stem from the placebo effect, these sham-controlled trials should be considered as offering potential direct benefit to participants. If scientific evidence demonstrates the positive effect of placebo from sham interventions on other conditions, sham-controlled trials of interventions for the treatment of these conditions should be considered to have prospects of benefit as well. This potential benefit should be taken into account by research ethics committees in risk-benefit analyses, and be included in informed consent documents.
C1 [Brim, Remy L.; Miller, Franklin G.] NIH, Dept Bioeth, Bethesda, MD 20892 USA.
RP Miller, FG (reprint author), NIH, Dept Bioeth, 10 Ctr Dr,Bldg 10,Rm 1C118, Bethesda, MD 20892 USA.
EM FMiller@cc.nih.gov
FU National Institutes of Health Clinical Center
FX This research was supported by the intramural research program of the
National Institutes of Health Clinical Center.
NR 27
TC 5
Z9 5
U1 1
U2 15
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0306-6800
EI 1473-4257
J9 J MED ETHICS
JI J. Med. Ethics
PD NOV
PY 2013
VL 39
IS 11
BP 703
EP 707
DI 10.1136/medethics-2012-101045
PG 5
WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical
SC Social Sciences - Other Topics; Medical Ethics; Social Issues;
Biomedical Social Sciences
GA 240HX
UT WOS:000326087200012
PM 23239742
ER
PT J
AU Plazinska, A
Kolinski, M
Wainer, IW
Jozwiak, K
AF Plazinska, Anita
Kolinski, Michal
Wainer, Irving W.
Jozwiak, Krzysztof
TI Molecular interactions between fenoterol stereoisomers and derivatives
and the beta(2)-adrenergic receptor binding site studied by docking and
molecular dynamics simulations
SO JOURNAL OF MOLECULAR MODELING
LA English
DT Article
DE beta(2) adrenergic receptor; GPCRs; Docking; Fenoterol; Molecular
dynamics; Stereoisomers
ID BETA-ADRENERGIC-RECEPTOR; PROTEIN-COUPLED RECEPTOR; HIGH-AFFINITY
BINDING; STRUCTURE PREDICTION; BETA-2-ADRENERGIC RECEPTOR;
CRYSTAL-STRUCTURE; PARTIAL AGONISTS; FIELD ANALYSIS; AMINO-ACID;
ACTIVATION
AB The beta(2) adrenergic receptor (beta(2)-AR) has become a model system for studying the ligand recognition process and mechanism of the G protein coupled receptors activation. In the present study stereoisomers of fenoterol and some of its derivatives (N = 94 molecules) were used as molecular probes to identify differences in stereo-recognition interactions between beta(2)-AR and structurally similar agonists. The present study aimed at determining the 3D molecular models of the fenoterol derivative-beta(2)-AR complexes. Molecular models of beta(2)-AR have been developed by using the crystal structure of the human beta(2)-AR T4 lysozyme fusion protein with bound (S)-carazolol (PDB ID: 2RH1) and more recently reported structure of a nanobody-stabilized active state of the beta(2)-AR with the bound full agonist BI-167107 (PDB ID: 3P0G). The docking procedure allowed us to study the similarities and differences in the recognition binding site(s) for tested ligands. The agonist molecules occupied the same binding region, between TM III, TM V, TM VI and TM VII. The residues identified by us during docking procedure (Ser203, Ser207, Asp113, Lys305, Asn312, Tyr308, Asp192) were experimentally indicated in functional and biophysical studies as being very important for the agonist-receptor interactions. Moreover, the additional space, an extension of the orthosteric pocket, was identified and described. Furthermore, the molecular dynamics simulations were used to study the molecular mechanism of interaction between ligands ((R,R')- and (S,S')-fenoterol) and beta(2)-AR. Our research offers new insights into the ligand stereoselective interaction with one of the most important GPCR member. This study may also facilitate the design of improved selective medications, which can be used to treat, prevent and control heart failure symptoms.
C1 [Plazinska, Anita; Kolinski, Michal; Jozwiak, Krzysztof] Med Univ Lublin, Lab Med Chem & Neuroengn, PL-20093 Lublin, Poland.
[Kolinski, Michal] Polish Acad Sci, Mossakowski Med Res Ctr, Bioinformat Lab, PL-02106 Warsaw, Poland.
[Wainer, Irving W.] NIA, Lab Clin Invest, Baltimore, MD 21224 USA.
RP Jozwiak, K (reprint author), Med Univ Lublin, Lab Med Chem & Neuroengn, Ul Chodzki 4A, PL-20093 Lublin, Poland.
EM krzysztof.jozwiak@umlub.pl
OI Plazinska, Anita/0000-0002-3698-2574
FU Polish Ministry of Science and Higher Education [N N405 617238];
Foundation for Polish Science [TEAM 2009-4/5, FOCUS 4/2006]
FX The work was supported by the Polish Ministry of Science and Higher
Education (Grant no. N N405 617238), by the Foundation for Polish
Science (TEAM 2009-4/5 and FOCUS 4/2006 programmes), and using the
equipment purchased within the Project "The equipment of innovative
laboratories doing research on new medicines used in the therapy of
civilization and neoplastic diseases" within the Operational Program
Development of Eastern Poland 2007- 2013, Priority Axis I Modern
Economy, Operations I. 3 Innovation Promotion. The research was also
supported in part by the Intramural Research Program of the National
Institutes of Health National Institute on Aging; by the National
Institutes of Health National Institute on Aging [Contract N01-AG31009].
NR 43
TC 10
Z9 10
U1 0
U2 25
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1610-2940
EI 0948-5023
J9 J MOL MODEL
JI J. Mol. Model.
PD NOV
PY 2013
VL 19
IS 11
BP 4919
EP 4930
DI 10.1007/s00894-013-1981-y
PG 12
WC Biochemistry & Molecular Biology; Biophysics; Chemistry,
Multidisciplinary; Computer Science, Interdisciplinary Applications
SC Biochemistry & Molecular Biology; Biophysics; Chemistry; Computer
Science
GA 241UH
UT WOS:000326193200032
PM 24043542
ER
PT J
AU Nicastro, HL
Firestone, GL
Bjeldanes, LF
AF Nicastro, Holly L.
Firestone, Gary L.
Bjeldanes, Leonard F.
TI 3,3 '-Diindolylmethane rapidly and selectively inhibits hepatocyte
growth factor/c-Met signaling in breast cancer cells
SO JOURNAL OF NUTRITIONAL BIOCHEMISTRY
LA English
DT Article
DE 3,3 '-diindolylmethane; Akt; c-Met; Breast cancer
ID TYROSINE KINASE; EPIDEMIOLOGIC EVIDENCE; BRASSICA VEGETABLES;
PROSTATE-CANCER; KAPPA-B; EXPRESSION; ACTIVATION; APOPTOSIS; RECEPTOR;
RISK
AB 3,3'-Diindolylmethane (DIM), an indole derivative from vegetables of the Brassica genus, has antiproliferative activity in breast cancer cells. Part of this activity is thought to be due to DIM inhibition of Akt signaling, but an upstream mechanism of DIM-induced Akt inhibition has not been described. The goals of this study were to investigate the kinetics of inhibition of Akt by physiologically relevant concentrations of DIM and to identify an upstream factor that mediates this effect. Here we report that DIM (5-25 mu M) inhibited Akt activation from 30 min to 24 h in tumorigenic MDA-MB-231 cells but did not inhibit Ala activation in non-tumorigenic preneoplastic MCF10AT cells. DIM inhibited hepatocyte growth factor (HGF)-induced Akt activation by up to 46%, cell migration by 66% and cell proliferation by up to 54%, but did not inhibit induction of Akt by epidermal growth factor or insulin-like growth factor-1. DIM decreased phosphorylation of the HGF receptor, c-Met, at tyrosines 1234 and 1235, indicating decreased activation of the receptor. This decrease was reversed by pretreatment with inhibitors of p38 or calcineurin. Our results demonstrate the important role of HGF and c-Met in DIM's anti-proliferative effect on breast cancer cells and suggest that DIM could have preventive or clinical value as an inhibitor of c-Met signaling. (C) 2013 Elsevier Inc. All rights reserved.
C1 [Nicastro, Holly L.; Bjeldanes, Leonard F.] Univ Calif Berkeley, Dept Nutr Sci & Toxicol, Berkeley, CA 94720 USA.
[Firestone, Gary L.] Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA.
RP Nicastro, HL (reprint author), NCI, Canc Prevent Fellowship Program, Canc Prevent Div, Rockville, MD 20852 USA.
EM holly.nicastro@nih.gov
FU National Institutes of Health [CA 69056]; California Breast Cancer
Research Program [14GB-0142]
FX Grant CA 69056 from the National Institutes of Health, fellowship
support for H.L.N. from California Breast Cancer Research Program
14GB-0142.
NR 42
TC 8
Z9 8
U1 1
U2 8
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0955-2863
EI 1873-4847
J9 J NUTR BIOCHEM
JI J. Nutr. Biochem.
PD NOV
PY 2013
VL 24
IS 11
BP 1882
EP 1888
DI 10.1016/j.jnutbio.2013.05.004
PG 7
WC Biochemistry & Molecular Biology; Nutrition & Dietetics
SC Biochemistry & Molecular Biology; Nutrition & Dietetics
GA 241AV
UT WOS:000326139700012
PM 23968581
ER
PT J
AU Maggio, M
Cattabiani, C
Lauretani, F
Bandinelli, S
De Vita, F
Dall'Aglio, E
Corsonello, A
Lattanzio, F
Paolisso, G
Ferrucci, L
Ceda, GP
AF Maggio, Marcello
Cattabiani, Chiara
Lauretani, Fulvio
Bandinelli, Stefania
De Vita, Francesca
Dall'Aglio, Elisabetta
Corsonello, Andrea
Lattanzio, Fabrizia
Paolisso, Giuseppe
Ferrucci, Luigi
Ceda, Gian Paolo
TI Insulin-Like Growth Factor-1 Bioactivity Plays a Prosurvival Role in
Older Participants
SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL
SCIENCES
LA English
DT Article
DE IGF-1 bioactivity; IGF-binding proteins; Mortality; Older participants
ID FACTOR-BINDING PROTEIN-1; ACUTE MYOCARDIAL-INFARCTION; IGF-I;
NITRIC-OXIDE; ELDERLY-MEN; FACTOR AXIS; LIFE-SPAN; CARDIOVASCULAR
MORTALITY; COLORECTAL-CANCER; RANCHO-BERNARDO
AB The aim of this study was to address the intriguing issue of the role of the insulin-like growth factor (IGF)-1 system in longevity looking at the role of different components of IGF system. Vital status was ascertained in 1,197 men and women aged greater than or equal to 65 years from the InCHIANTI study. Hormonal levels were categorized into quartiles, and ratio of IGF-1 to IGF-binding protein (IGFBP)-1 was calculated. The relationship between hormones and mortality was tested by Cox proportional hazard models adjusted for age, sex, and confounders. During the 8-year follow-up period, 240 died and 957 survived. Lowest quartiles of IGF-1 and IGFBP-1 were considered as reference. Compared with the lowest quartiles, IGF-1 in upper quartiles was a negative predictor of mortality independent of age and sex (p = .01) but not independent of IGFBP-1 and other confounders. IGFBP-1 in second-third quartiles was negatively associated and that in the fourth quartiles was positively associated with risk of death. IGF-1/IGFBP-1 ratio in the lowest quartiles was a strong positive predictor of mortality, in age-and sex-adjusted model (p = .005), and independent of additional confounders (p = .037). High IGFBP-1 and low IGF-1/IGFBP-1 ratio are associated with all-cause mortality in older population.
C1 [Maggio, Marcello; Cattabiani, Chiara; De Vita, Francesca; Dall'Aglio, Elisabetta; Ceda, Gian Paolo] Univ Parma, Sect Geriatr, Dept Clin & Expt Med, I-43100 Parma, Italy.
[Maggio, Marcello; Lauretani, Fulvio; Ceda, Gian Paolo] Univ Hosp Parma, Geriatr Rehabil Dept, Geriatr Unit, Parma, Italy.
[Bandinelli, Stefania] Azienda Sanitaria Firenze, Florence, Italy.
[Corsonello, Andrea] INRCA, Unit Geriatr Pharmacoepidemiol, Cosenza, Italy.
[Lattanzio, Fabrizia] INRCA Ancona, Sci Direct, Ancona, Italy.
[Paolisso, Giuseppe] Univ Naples 2, Dept Geriatr & Metab Dis, Naples, Italy.
[Ferrucci, Luigi] NIA, NIH, Baltimore, MD 21224 USA.
RP Maggio, M (reprint author), Univ Parma, Sect Geriatr, Dept Clin & Expt Med, Via Gramsci 14, I-43100 Parma, Italy.
EM marcellomaggio2001@yahoo.it
RI Lauretani, Fulvio/K-5115-2016;
OI Paolisso, Giuseppe/0000-0002-2137-455X; Lauretani,
Fulvio/0000-0002-5287-9972; Ceda, Gian Paolo/0000-0002-9648-8295
FU Italian Ministry of Health [ICS 110.1/RS97.71, RF-2010-2312659]; U.S.
National Institute on Aging [N01-AG-916413, N01-AG-821336]; Intramural
Research Program of the U.S. National Institute on Aging [263 MD 916413,
263 MD 821336]; Emilia Romagna Region
FX The InCHIANTI study was supported as a "targeted project" (ICS
110.1/RS97.71) by the Italian Ministry of Health, the U.S. National
Institute on Aging (contracts N01-AG-916413 and N01-AG-821336), in part,
the Intramural Research Program of the U.S. National Institute on Aging
(contracts 263 MD 916413 and 263 MD 821336), and grant RF-2010-2312659
from the Italian Ministry of Health and Emilia Romagna Region. None of
the sponsoring institutions interfered with the collection, analysis,
presentation, or interpretation of the data reported here.
NR 61
TC 4
Z9 4
U1 0
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 2013
VL 68
IS 11
BP 1342
EP 1350
DI 10.1093/gerona/glt045
PG 9
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 239BP
UT WOS:000325996800004
PM 23671288
ER
PT J
AU Rosso, AL
Studenski, SA
Chen, WG
Aizenstein, HJ
Alexander, NB
Bennett, DA
Black, SE
Camicioli, R
Carlson, MC
Ferrucci, L
Guralnik, JM
Hausdorff, JM
Kaye, J
Launer, LJ
Lipsitz, LA
Verghese, J
Rosano, C
AF Rosso, Andrea L.
Studenski, Stephanie A.
Chen, Wen G.
Aizenstein, Howard J.
Alexander, Neil B.
Bennett, David A.
Black, Sandra E.
Camicioli, Richard
Carlson, Michelle C.
Ferrucci, Luigi
Guralnik, Jack M.
Hausdorff, Jeffrey M.
Kaye, Jeff
Launer, Lenore J.
Lipsitz, Lewis A.
Verghese, Joe
Rosano, Caterina
TI Aging, the Central Nervous System, and Mobility
SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL
SCIENCES
LA English
DT Article
DE Motor control; Central nervous system; Mobility
ID FUNCTIONING OLDER-ADULTS; MILD COGNITIVE IMPAIRMENT; LOWER-EXTREMITY
FUNCTION; GAIT SPEED; DUAL-TASK; EXECUTIVE FUNCTION; FALL RISK; BRAIN;
DECLINE; WALKING
AB Background. Mobility limitations are common and hazardous in community-dwelling older adults but are largely understudied, particularly regarding the role of the central nervous system (CNS). This has limited development of clearly defined pathophysiology, clinical terminology, and effective treatments. Understanding how changes in the CNS contribute to mobility limitations has the potential to inform future intervention studies.
Methods. A conference series was launched at the 2012 conference of the Gerontological Society of America in collaboration with the National Institute on Aging and the University of Pittsburgh. The overarching goal of the conference series is to facilitate the translation of research results into interventions that improve mobility for older adults.
Results. Evidence from basic, clinical, and epidemiological studies supports the CNS as an important contributor to mobility limitations in older adults without overt neurologic disease. Three main goals for future work that emerged were as follows: (a) develop models of mobility limitations in older adults that differentiate aging from disease-related processes and that fully integrate CNS with musculoskeletal contributors; (b) quantify the contribution of the CNS to mobility loss in older adults in the absence of overt neurologic diseases; (c) promote cross-disciplinary collaboration to generate new ideas and address current methodological issues and barriers, including real-world mobility measures and life-course approaches.
Conclusions. In addition to greater cross-disciplinary research, there is a need for new approaches to training clinicians and investigators, which integrate concepts and methodologies from individual disciplines, focus on emerging methodologies, and prepare investigators to assess complex, multisystem associations.
C1 [Rosso, Andrea L.; Rosano, Caterina] Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15213 USA.
[Studenski, Stephanie A.] Univ Pittsburgh, Sch Med, Div Geriatr Med, Pittsburgh, PA 15213 USA.
[Chen, Wen G.] NIA, Div Neurosci, Bethesda, MD 20892 USA.
[Aizenstein, Howard J.] Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 15213 USA.
[Alexander, Neil B.] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA.
[Bennett, David A.] Rush Univ, Med Ctr, Rush Alzheimers Dis Ctr, Dept Neurol Sci, Chicago, IL 60612 USA.
[Black, Sandra E.] Univ Toronto, Sunnybrook Hlth Sci Ctr, Div Neurol, Dept Med, Toronto, ON M5S 1A1, Canada.
[Camicioli, Richard] Univ Alberta, Dept Med, Div Neurol, Edmonton, AB T6G 2R3, Canada.
[Carlson, Michelle C.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA.
[Ferrucci, Luigi] NIA, Clin Res Branch, NIH, Baltimore, MD 21224 USA.
[Guralnik, Jack M.] Univ Maryland, Sch Med, Dept Epidemiol & Publ Hlth, Baltimore, MD 21201 USA.
[Hausdorff, Jeffrey M.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Hausdorff, Jeffrey M.] Tel Aviv Sourasky Med Ctr, Dept Neurol, Tel Aviv, Israel.
[Kaye, Jeff] Oregon Hlth & Sci Univ, Dept Neurol, Portland, OR 97201 USA.
[Launer, Lenore J.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
[Lipsitz, Lewis A.] Beth Israel Deaconess Med Ctr, Div Gerontol, Boston, MA 02215 USA.
[Lipsitz, Lewis A.] Hebrew Senior Life, Inst Aging Res, Boston, MA USA.
[Lipsitz, Lewis A.] Harvard Univ, Sch Med, Boston, MA USA.
[Verghese, Joe] Yeshiva Univ, Dept Neurol, Albert Einstein Coll Med, New York, NY 10033 USA.
RP Rosano, C (reprint author), Univ Pittsburgh, Grad Sch Publ Hlth, Ctr Aging & Populat Hlth, 130 North Bellefield St,Room 507, Pittsburgh, PA 15213 USA.
EM rosanoc@edc.pitt.edu
OI Rosso, Andrea/0000-0001-5890-9856; Black, Sandra/0000-0001-7093-8289;
Kaye, Jeffrey/0000-0002-9971-3478; Rosano, Caterina/0000-0002-0909-1506;
Rosano, Caterina/0000-0002-4271-6010; Camicioli,
Richard/0000-0003-2977-8660
FU National Institute on Aging [U13-AG-041613-01, T32-AG-000181];
University of Pittsburgh Claude D. Pepper Older Americans Independence
Center (National Institute on Aging) [P30-AG-024827]
FX This work was supported by a co-operative conference grant (National
Institute on Aging, U13-AG-041613-01), the University of Pittsburgh
Claude D. Pepper Older Americans Independence Center (National Institute
on Aging, P30-AG-024827), and a postdoctoral training grant (National
Institute on Aging, T32-AG-000181).
NR 57
TC 45
Z9 45
U1 4
U2 25
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 2013
VL 68
IS 11
BP 1379
EP 1386
DI 10.1093/gerona/glt089
PG 8
WC Geriatrics & Gerontology; Gerontology
SC Geriatrics & Gerontology
GA 239BP
UT WOS:000325996800007
PM 23843270
ER
PT J
AU Sutin, AR
Zonderman, AB
Ferrucci, L
Terracciano, A
AF Sutin, Angelina R.
Zonderman, Alan B.
Ferrucci, Luigi
Terracciano, Antonio
TI Personality Traits and Chronic Disease: Implications for Adult
Personality Development
SO JOURNALS OF GERONTOLOGY SERIES B-PSYCHOLOGICAL SCIENCES AND SOCIAL
SCIENCES
LA English
DT Article
DE Disease burden; Illness; Openness; Personality change; Personality
traits
ID ALZHEIMER-DISEASE; LIFE-SPAN; OLD-AGE; HEALTH; CONSCIENTIOUSNESS;
DEPRESSION; METAANALYSIS; IMPULSIVITY; PERSPECTIVE; IMPAIRMENT
AB Objective. Personality traits have been associated with chronic disease. Less is known about the longitudinal relation between personality and disease and whether chronic disease is associated with changes in personality.
Method. Participants from the Baltimore Longitudinal Study of Aging (N = 2,008) completed the Revised NEO Personality Inventory and a standard medical interview at regularly scheduled visits; the Charlson Comorbidity Index, a weighted sum of 19 serious diseases, was derived from this interview. Using data from 6,685 visits, we tested whether personality increased risk of disease and whether disease was associated with personality change.
Results. Measured concurrently, neuroticism and conscientiousness were associated with greater disease burden. The impulsiveness facet of neuroticism was the strongest predictor of developing disease across the follow-up period: For every standard deviation increase in impulsiveness, there was a 26% increased risk of developing disease and a 36% increased risk of getting more ill. Personality traits changed only modestly with disease: As participants developed chronic illnesses, they became more conservative (decreased openness).
Discussion. This research indicates that personality traits confer risk for disease, in part, through health-risk behaviors. These traits, however, were relatively resistant to the effect of serious disease.
C1 [Sutin, Angelina R.] Florida State Univ, Coll Med, Dept Med Humanities & Social Sci, Tallahassee, FL 32306 USA.
[Sutin, Angelina R.; Terracciano, Antonio] NIA, NIH, Baltimore, MD 21224 USA.
[Zonderman, Alan B.] NIA, Lab Behav Neurosci, NIH, Baltimore, MD 21224 USA.
[Ferrucci, Luigi] NIA, Clin Res Branch, NIH, Baltimore, MD 21224 USA.
[Terracciano, Antonio] Florida State Univ, Coll Med, Dept Geriatr, Tallahassee, FL 32306 USA.
RP Sutin, AR (reprint author), Florida State Univ, Coll Med, Dept Med Humanities & Social Sci, NIH,DHHS, 1115 W Call St, Tallahassee, FL 32306 USA.
EM angelina.sutin@med.fsu.edu
OI Zonderman, Alan B/0000-0002-6523-4778
FU Intramural Research Program of the National Institute on Aging, National
Institutes of Health
FX This research was supported, in part, by the Intramural Research Program
of the National Institute on Aging, National Institutes of Health.
NR 58
TC 22
Z9 22
U1 4
U2 20
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1079-5014
EI 1758-5368
J9 J GERONTOL B-PSYCHOL
JI J. Gerontol. Ser. B-Psychol. Sci. Soc. Sci.
PD NOV
PY 2013
VL 68
IS 6
BP 912
EP 920
DI 10.1093/geronb/gbt036
PG 9
WC Geriatrics & Gerontology; Gerontology; Psychology; Psychology,
Multidisciplinary
SC Geriatrics & Gerontology; Psychology
GA 240TQ
UT WOS:000326120600007
PM 23685925
ER
PT J
AU Ginsberg, MD
Palesch, YY
Hill, MD
Martin, RH
Moy, CS
Barsan, WG
Waldman, BD
Tamariz, D
Ryckborst, KJ
AF Ginsberg, Myron D.
Palesch, Yuko Y.
Hill, Michael D.
Martin, Renee H.
Moy, Claudia S.
Barsan, William G.
Waldman, Bonnie D.
Tamariz, Diego
Ryckborst, Karla J.
CA ALIAS
Neurological Emergencies Treatment
TI High-dose albumin treatment for acute ischaemic stroke (ALIAS) part 2: a
randomised, double-blind, phase 3, placebo-controlled trial
SO LANCET NEUROLOGY
LA English
DT Article
ID FOCAL CEREBRAL-ISCHEMIA; MARKED NEUROPROTECTIVE EFFICACY;
TISSUE-PLASMINOGEN ACTIVATOR; LOCAL VASCULAR DYNAMICS;
PLATELET-AGGREGATION; GLYCINE ANTAGONIST; SERUM-ALBUMIN; PILOT TRIAL;
RAT MODEL; THERAPY
AB Background In animal models of ischaemic stroke, 25% albumin reduced brain infarction and improved neurobehavioural outcome. In a pilot clinical trial, albumin doses as high as 2 g/kg were safely tolerated. We aimed to assess whether albumin given within 5 h of the onset of acute ischaemic stroke increased the proportion of patients with a favourable outcome.
Methods We did a randomised, double-blind, parallel-group, phase 3, placebo-controlled trial between Feb 27, 2009, and Sept 10, 2012, at 69 sites in the USA, 13 sites in Canada, two sites in Finland, and five sites in Israel. Patients aged 18-83 years with ischaemic (ie, non-haemorrhagic) stroke with a baseline National Institutes of Health stroke scale (NIHSS) score of 6 or more who could be treated within 5 h of onset were randomly assigned (1:1), via a central web-based randomisation process with a biased coin minimisation approach, to receive 25% albumin (2 g [8 mL] per kg; maximum dose 750 mL) or the equivalent volume of isotonic saline. All study personnel and participants were masked to the identity of the study drug. The primary endpoint was favourable outcome, defined as either a modified Rankin scale score of 0 or 1, or an NIHSS score of 0 or 1, or both, at 90 days. Analysis was by intention to treat. Thrombolytic therapies were permitted. This trial is registered with ClinicalTrials.gov, number NCT00235495.
Findings 422 participants were randomly assigned to receive albumin and 419 to receive saline. On Sept 12, 2012, the trial was stopped early for futility (n=841). The primary outcome did not differ between patients in the albumin group and those in the saline group (186 [44%] vs 185 [44%]; risk ratio 0.96, 95% CI 0.84-1.10, adjusted for baseline NIHSS score and thrombolysis stratum). Mild-to-moderate pulmonary oedema was more common in patients given albumin than in those given saline (54 [13%] of 412 vs 5 [1%] of 412 patients); symptomatic intracranial haemorrhage within 24 h was also more common in patients in the albumin group than in the placebo group (17 [4%] of 415 vs 7 [2%] of 414 patients). Although the rate of favourable outcome in patients given albumin remained consistent at 44-45% over the course of the trial, the cumulative rate of favourable outcome in patients given saline rose steadily from 31% to 44%.
Interpretation Our findings show no clinical benefit of 25% albumin in patients with ischaemic stroke; however, they should not discourage further efforts to identify effective strategies to protect the ischaemic brain, especially because of preclinical literature showing convincing proof-of-principle for the possibility of this outcome.
C1 [Ginsberg, Myron D.; Tamariz, Diego] Univ Miami, Miller Sch Med, Dept Neurol, Miami, FL 33101 USA.
[Palesch, Yuko Y.; Martin, Renee H.; Waldman, Bonnie D.] Med Univ S Carolina, Dept Publ Hlth Sci, Data Coordinat Unit, Charleston, SC 29425 USA.
[Hill, Michael D.; Ryckborst, Karla J.] Univ Calgary, Dept Clin Neurosci, Calgary Stroke Program, Calgary, AB, Canada.
[Hill, Michael D.; Ryckborst, Karla J.] Univ Calgary, Hotchkiss Brain Inst, Dept Community Hlth Serv, Dept Med,Dept Radiol, Calgary, AB, Canada.
[Hill, Michael D.; Ryckborst, Karla J.] Foothills Prov Gen Hosp, Calgary, AB T2N 2T9, Canada.
[Moy, Claudia S.] Natl Inst Neurol Disorders & Stroke, Off Clin Res, Bethesda, MD USA.
[Barsan, William G.] Univ Michigan, Dept Emergency Med, Ann Arbor, MI 48109 USA.
RP Ginsberg, MD (reprint author), Univ Miami, Miller Sch Med, Dept Neurol D4 5, POB 016960, Miami, FL 33101 USA.
EM mginsberg@med.miami.edu
RI Hill, Michael/C-9073-2012
OI Hill, Michael/0000-0002-6269-1543
FU National Institute of Neurological Disorders and Stroke, US National
Institutes of Health; Baxter Healthcare Corporation
FX Funding National Institute of Neurological Disorders and Stroke, US
National Institutes of Health; and Baxter Healthcare Corporation.
NR 54
TC 44
Z9 48
U1 0
U2 13
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1474-4422
EI 1474-4465
J9 LANCET NEUROL
JI Lancet Neurol.
PD NOV
PY 2013
VL 12
IS 11
BP 1049
EP 1058
DI 10.1016/S1474-4422(13)70223-0
PG 10
WC Clinical Neurology
SC Neurosciences & Neurology
GA 239ZC
UT WOS:000326063500007
PM 24076337
ER
PT J
AU Mukamal, KJ
Wilk, JB
Biggs, ML
Jensen, MK
Ix, JH
Kizer, JR
Tracy, RP
Zieman, SJ
Mozaffarian, D
Psaty, BM
Siscovick, DS
Djousse, L
AF Mukamal, Kenneth J.
Wilk, Jemma B.
Biggs, Mary L.
Jensen, Majken K.
Ix, Joachim H.
Kizer, Jorge R.
Tracy, Russell P.
Zieman, Susan J.
Mozaffarian, Dariush
Psaty, Bruce M.
Siscovick, David S.
Djousse, Luc
TI Common FABP4 Genetic Variants and Plasma Levels of Fatty Acid Binding
Protein 4 in Older Adults
SO LIPIDS
LA English
DT Article
DE Fatty acid binding proteins; Metabolism; Genetics
ID METABOLIC SYNDROME; DIABETES RISK; ASSOCIATION; LOCI; MICE; OBESITY;
DESIGN
AB We examined common variants in the fatty acid binding protein 4 gene (FABP4) and plasma levels of FABP4 in adults aged 65 and older from the Cardiovascular Health Study. We genotyped rs16909187, rs1054135, rs16909192, rs10808846, rs7018409, rs2290201, and rs6992708 and measured circulating FABP4 levels among 3190 European Americans and 660 African Americans. Among European Americans, the minor alleles of six single nucleotide polymorphisms (SNP) were associated with lower FABP4 levels (all p a parts per thousand currency sign 0.01). Among African Americans, the SNP with the lowest minor allele frequency was associated with lower FABP4 levels (p = 0.015). The C-A haplotype of rs16909192 and rs2290201 was associated with lower FABP4 levels in both European Americans (frequency = 16 %; p = 0.001) and African Americans (frequency = 8 %; p = 0.04). The haplotype combined a SNP in the first intron with one in the 3'untranslated region. However, the alleles associated with lower FABP4 levels were associated with higher fasting glucose in meta-analyses from the MAGIC consortium. These results demonstrate associations of common SNP and haplotypes in the FABP4 gene with lower plasma FABP4 but higher fasting glucose levels.
C1 [Mukamal, Kenneth J.] Beth Israel Deaconess Med Ctr, Div Gen Med & Primary Care, Boston, MA 02215 USA.
[Wilk, Jemma B.; Djousse, Luc] Brigham & Womens Hosp, Dept Med, Div Aging, Boston, MA 02120 USA.
[Wilk, Jemma B.; Mozaffarian, Dariush; Djousse, Luc] Harvard Univ, Sch Med, Boston, MA 02120 USA.
[Biggs, Mary L.] Univ Washington, Sch Publ Hlth, Dept Biostat, Seattle, WA 98195 USA.
[Jensen, Majken K.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Ix, Joachim H.] Univ Calif San Diego, Nephrol Sect, Vet Affairs San Diego Healthcare Syst, San Diego, CA 92103 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.
[Kizer, Jorge R.] Albert Einstein Coll Med, Dept Med, New York, NY USA.
[Kizer, Jorge R.] Albert Einstein Coll Med, Dept Epidemiol & Publ Hlth, New York, NY USA.
[Tracy, Russell P.] Univ Vermont, Coll Med, Dept Pathol & Biochem, Burlington, VT USA.
[Zieman, Susan J.] NIA, NIH, Bethesda, MD 20892 USA.
[Mozaffarian, Dariush] Brigham & Womens Hosp, Div Cardiovasc Med, Boston, MA 02120 USA.
[Psaty, Bruce M.; Siscovick, David S.] Univ Washington, Dept Med, Cardiovasc Hlth Res Unit, Seattle, WA USA.
[Psaty, Bruce M.; Siscovick, David S.] Univ Washington, Dept Epidemiol, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.
[Psaty, Bruce M.; Siscovick, David S.] Univ Washington, Dept Hlth Serv, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA.
[Psaty, Bruce M.] Grp Hlth Cooperat Puget Sound, Grp Hlth Res Inst, Seattle, WA 98121 USA.
[Djousse, Luc] Boston Vet Affairs Healthcare Syst, Ctr Geriatr Res Educ & Clin, Boston, MA USA.
[Djousse, Luc] Boston Vet Affairs Healthcare Syst, Massachusetts Vet Epidemiol & Res Informat Ctr, Boston, MA USA.
RP Wilk, JB (reprint author), Brigham & Womens Hosp, Dept Med, Div Aging, 1620 Tremont St,3rd Floor, Boston, MA 02120 USA.
EM jemmawilk@gmail.com; ldjousse@partners.org
RI Djousse, Luc/F-5033-2017
OI Djousse, Luc/0000-0002-9902-3047
FU NHLBI [N01-HC-65226, HHSN268201200036C, N01-HC-85239, N01-HC-85079,
N01-HC-85080, N01-HC-85081, N01-HC-85082, N01-HC-85083, N01-HC-85084,
N01-HC-85085, N01-HC-85086, N01-HC-35129, N01 HC-15103, N01 HC-55222,
N01-HC-75150, N01-HC-45133, HL094555, HL080295]; National Institute on
Aging (NIA) [AG-023629, AG-15928, AG-20098, AG-027058]
FX Funding for CARe genotyping was provided by NHLBI Contract N01-HC-65226.
The research reported in this article was supported by contracts
HHSN268201200036C, N01-HC-85239, N01-HC-85079 through N01-HC-85086,
N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133,
and grants HL094555 (to Drs. Djousse, Ix, Mukamal, Zieman, and Kizer)
and HL080295 from the NHLBI, with additional contribution from the
National Institute of Neurological Disorders and Stroke (NINDS).
Additional support was provided through AG-023629, AG-15928, AG-20098,
and AG-027058 from the National Institute on Aging (NIA). A full list of
principal CHS investigators and institutions can be found at
http://www.chs-nhlbi.org/pi.htm.
NR 20
TC 3
Z9 3
U1 1
U2 4
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 0024-4201
EI 1558-9307
J9 LIPIDS
JI Lipids
PD NOV
PY 2013
VL 48
IS 11
BP 1169
EP 1175
DI 10.1007/s11745-013-3838-7
PG 7
WC Biochemistry & Molecular Biology; Nutrition & Dietetics
SC Biochemistry & Molecular Biology; Nutrition & Dietetics
GA 239TD
UT WOS:000326047500010
PM 24043587
ER
PT J
AU Wang, LD
Bi, XL
Song, X
Pohl, NM
Cheng, YL
Zhou, YX
Shears, S
Ansong, E
Xing, MT
Wang, SM
Xu, XC
Huang, P
Xu, LY
Wang, L
Fan, ZM
Zhao, XK
Dong, HL
Meltzer, SJ
Ding, I
Yang, WC
AF Wang, Li-Dong
Bi, Xiuli
Song, Xin
Pohl, Nicole M.
Cheng, Yulan
Zhou, Yixing
Shears, Stephen
Ansong, Emmanuel
Xing, Mengtao
Wang, Shaomeng
Xu, Xiao-Chun
Huang, Peng
Xu, Liyan
Wang, Liang
Fan, Zongmin
Zhao, Xueke
Dong, Huali
Meltzer, Stephen J.
Ding, Ivan
Yang, Wancai
TI A Sequence Variant in the Phospholipase C Epsilon C2 Domain Is
Associated With Esophageal Carcinoma and Esophagitis
SO MOLECULAR CARCINOGENESIS
LA English
DT Article
DE phospholipase C epsilon; esophageal cancer; esophagitis
ID SQUAMOUS-CELL CARCINOMA; CRUCIAL ROLE; DEPENDENT ACTIVATION; RAS;
CANCER; RHO; INFLAMMATION; DISTINCT; GROWTH; PLCE1
AB A single-nucleotide polymorphism (rs2274223: A5780G:His1927Arg) in the phospholipase C epsilon gene (PLCE) was recently identified as a susceptibility locus for esophageal cancer in Chinese subjects. To determine the underlying mechanisms of PLCE and this SNP in esophageal carcinogenesis, we analyzed PLCE genotypes, expression, and their correlation in esophageal cancer cell lines, non-transformed esophageal cells, 58 esophageal squamous cell carcinomas and 10,614 non-cancer subjects from China. We found that the G allele (AG or GG) was associated with increased PLCE mRNA and protein expression in esophageal cancer tissues and in esophageal cancer cell lines. G allele was also associated with higher enzyme activity, which might be associated with increased protein expression. Quantitative analysis of the C2 domain sequences revealed that A:G allelic imbalance was strongly linked to esophageal malignancy. Moreover, the analysis of 10,614 non-cancer subjects demonstrated that the G allele was strongly associated with moderate to severe esophagitis in the subjects from the high-incidence areas of China (OR 6.03, 95% CI 1.59-22.9 in high-incidence area vs. OR 0.74, 95% CI 0.33-1.64 in low-incidence area; P=0.008). In conclusion, the PLCE gene, particularly the 5780G allele, might play a pivotal role in esophageal carcinogenesis via upregulating PLCE mRNA, protein, and enzyme activity, and augmenting inflammatory process in esophageal epithelium. Thus, 5780G allele may constitute a promising biomarker for esophageal squamous cell carcinoma risk stratification, early detection, and progression prediction. (c) 2013 Wiley Periodicals, Inc.
C1 [Wang, Li-Dong; Song, Xin; Wang, Liang; Zhao, Xueke; Ding, Ivan; Yang, Wancai] Xinxiang Med Univ, Dept Pathol, Xinxiang 453003, Peoples R China.
[Wang, Li-Dong; Fan, Zongmin] Zhengzhou Univ, Henan Key Lab Esophageal Canc Res, Affiliated Hosp 1, Zhengzhou 450052, Peoples R China.
[Bi, Xiuli; Pohl, Nicole M.; Ansong, Emmanuel; Xing, Mengtao; Yang, Wancai] Univ Illinois, Dept Pathol, Chicago, IL USA.
[Bi, Xiuli] Liaoning Univ, Sch Life Sci, Shenyang 110036, Peoples R China.
[Cheng, Yulan; Meltzer, Stephen J.] Johns Hopkins Univ, Sch Med, Dept Med, Div Gastroenterol, Baltimore, MD 21205 USA.
[Zhou, Yixing; Shears, Stephen] NIEHS, Inositol Signaling Grp, NIH, Res Triangle Pk, NC 27709 USA.
[Wang, Shaomeng] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA.
[Wang, Shaomeng] Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA.
[Wang, Shaomeng] Univ Michigan, Dept Pharmacol, Ann Arbor, MI 48109 USA.
[Wang, Shaomeng] Univ Michigan, Dept Med Chem, Ann Arbor, MI 48109 USA.
[Xu, Xiao-Chun] Univ Texas MD Anderson Canc Ctr, Dept Clin Canc Prevent, Houston, TX 77030 USA.
[Huang, Peng] Univ Texas MD Anderson Canc Ctr, Dept Mol Pathol, Houston, TX 77030 USA.
[Xu, Liyan] Shantou Univ Med Coll, Dept Pathol, Shantou, Peoples R China.
[Wang, Liang] Med Coll Wisconsin, Dept Pathol, Milwaukee, WI 53226 USA.
[Dong, Huali] Univ Illinois, Ctr Canc, Chicago, IL USA.
RP Yang, WC (reprint author), Xinxiang Med Univ, Dept Pathol, Xinxiang 453003, Peoples R China.
FU National Institutes of Health, USA [CA112081]; Xinxiang Medical
University; China National Natural Science Foundation [30670956,
30971133, 91229115]; Program of Liaoning Excellent Talents in University
(LETU) [LJQ2011002]; NIH/National Institute of Environmental Health
Sciences; [CA146799]; [DK087454]
FX Contract grant sponsor: National Institutes of Health, USA; Contract
grant number: CA112081 (to W. Yang); Contract grant sponsor:; Contract
grant number: CA146799 and DK087454 (to S.J. Meltzer); Contract grant
sponsor: Xinxiang Medical University Key Scientific Program 2009-5;
Contract grant sponsor: China National Natural Science Foundation;
Contract grant numbers: 30670956; 30971133 (to L. D. Wang); 91229115 (to
W. Yang); Contract grant sponsor: Program of Liaoning Excellent Talents
in University (LETU); Contract grant number: LJQ2011002 (to X. Bi);
Contract grant sponsor: Intramural Research Program of the NIH/National
Institute of Environmental Health Sciences (to S. Shears).
NR 26
TC 5
Z9 6
U1 3
U2 10
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 2013
VL 52
SU 1
SI SI
BP 80
EP 86
DI 10.1002/mc.22016
PG 7
WC Biochemistry & Molecular Biology; Oncology
SC Biochemistry & Molecular Biology; Oncology
GA 242DR
UT WOS:000326218100010
ER
PT J
AU Couce, ML
Boveda, MD
Garcia-Jimemez, C
Balmaseda, E
Vives, I
Castineiras, DE
Fernandez-Marmiesse, A
Fraga, JM
Mudd, SH
Corrales, FJ
AF Couce, Maria L.
Dolores Boveda, M.
Garcia-Jimemez, Concepcion
Balmaseda, Elena
Vives, Inmaculada
Castineiras, Daisy E.
Fernandez-Marmiesse, Ana
Fraga, Jose M.
Mudd, S. Harvey
Corrales, Fernando J.
TI Clinical and metabolic findings in patients with methionine
adenosyltransferase I/III deficiency detected by newborn screening
SO MOLECULAR GENETICS AND METABOLISM
LA English
DT Article
DE S-adenosylmethionine; Homocysteine; Newborn screening; Persistent
hypermethioninemia
ID S-ADENOSYLMETHIONINE; PERSISTENT HYPERMETHIONINEMIA; INBORN-ERRORS;
DEMYELINATION; PATHWAY
AB Persistent hypermethioninemia due to mutations in the MAT1A gene is often found during newborn screening (NBS) for homocystinuria due to cystathionine beta-synthase deficiency, however, outcomes and optimal management for these patients are not well established. We carried out a multicenter study of MAT I/III-deficient patients detected by NBS in four of the Spanish regional NBS programs. Data evaluated during NBS and follow-up for 18 patients included methionine and total homocysteine levels, clinical presentation parameters, genotypes, and development quotients. The birth prevalence was 1:1:22,874. At detection 16 of the 18 patients exhibited elevations of plasma methionine above 60 mu mol/L (mean 99.9 +/- 38 mu mol/L) and the mean value in confirmation tests was 301 mu mol/L (91-899) mu mol/L. All patients were asymptomatic. In four patients with more markedly elevated plasma methionines (>450 mu mol/L) total homocysteine values were slightly elevated (about 20 mu mol/L). The average follow-up period was 3 years 7 months (range: 2-123 months). Most patients (83%) were heterozygous for the autosomal dominant Arg264His mutation and, with one exception, presented relatively low circulating methionine concentrations (<400 mu M). Additional mutations identified in patients with mean confirmatory plasma methionines above 400 mu M were Arg199Cys. Leu355Arg, and a novel mutation, Thr288Ala. During continued follow-up, the patients have been asymptomatic, and, to date, no therapeutic interventions have been utilized. Therefore, the currently available evidence shows that hypermethioninemia due to heterozygous MAT1A mutations such as Arg264His is a mild condition for which no treatment is necessary. (C) 2013 Elsevier Inc. All rights reserved.
C1 [Couce, Maria L.] Univ Santiago de Compostela, Hosp Clin, Dept Pediat, Unit Diag & Treatment Congenital Metab Dis, Santiago De Compostela 15706, A Coruna, Spain.
[Dolores Boveda, M.; Castineiras, Daisy E.; Fernandez-Marmiesse, Ana] Univ Santiago de Compostela, Hosp Clin, Metab Lab, Unit Diag & Treatment Congenital Metab Dis, Santiago De Compostela 15706, A Coruna, Spain.
[Garcia-Jimemez, Concepcion] Hosp Miguel Servet, Serv Pediat, Metab Unit, Zaragoza, Spain.
[Balmaseda, Elena] Complejo Hosp Univ Albacete, Serv Pediat, Metab Unit, Albacete, Spain.
[Vives, Inmaculada] Hosp Univ Virgen de la Arrixaca, Serv Pediat, Metab Unit, Murcia, Spain.
[Fraga, Jose M.] Univ Santiago, Hosp Clin, Dept Pediat, Unit Diag & Treatment Congenital Metab Dis, Santiago De Compostela 15706, A Coruna, Spain.
[Mudd, S. Harvey] NIMH, Mol Biol Lab, Bethesda, MD 20892 USA.
[Corrales, Fernando J.] Univ Navarra, Ctr Appl Med Res, Proteon Unit, Div Hepatol & Gene Therapy, E-31080 Pamplona, Spain.
RP Couce, ML (reprint author), Univ Santiago de Compostela, Hosp Clin, Dept Pediat, Unit Diag & Treatment Congenital Metab Dis, A Choupana S-N, Santiago De Compostela 15706, A Coruna, Spain.
EM maria.luz.couce.pico@sergas.es; maria.boveda.fontan@sergas.es;
igarciaji@salud.aragon.es; elenabalmaseda@hotmail.com;
vivesmas@hotmail.com; daisy.castineiras.ramos@sergas.es;
amarmiesse@gmail.com; pdneonat@usc.es; muddh@mail.nih.gov;
fjcoriz@gmail.com
OI fraga, jose m/0000-0001-8897-3621
NR 22
TC 12
Z9 12
U1 0
U2 8
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1096-7192
EI 1096-7206
J9 MOL GENET METAB
JI Mol. Genet. Metab.
PD NOV
PY 2013
VL 110
IS 3
BP 218
EP 221
DI 10.1016/j.ymgme.2013.08.003
PG 4
WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research &
Experimental
SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental
Medicine
GA 239WZ
UT WOS:000326058000004
PM 23993429
ER
PT J
AU Lee, YM
Pan, CJ
Koeberl, DD
Mansfield, BC
Chou, JY
AF Lee, Young Mok
Pan, Chi-Jiunn
Koeberl, Dwight D.
Mansfield, Brian C.
Chou, Janice Y.
TI The upstream enhancer elements of the G6PC promoter are critical for
optimal G6PC expression in murine glycogen storage disease type Ia
SO MOLECULAR GENETICS AND METABOLISM
LA English
DT Article
DE Glycogen storage disease type I; Glucose-6-phosphatase; Adeno-associated
virus; Gene therapy
ID GENE-THERAPY; ADENOASSOCIATED-VIRUS; AAV; VECTORS; LIVER; TRANSDUCTION;
DEFICIENCY; MANAGEMENT; SERIES; MOUSE
AB Glycogen storage disease type-la (GSD-Ia) patients deficient in glucose-6-phosphatase-alpha (G6Pase-alpha or G6PC) manifest impaired glucose homeostasis characterized by fasting hypoglycemia, growth retardation, hepatomegaly, nephromegaly, hyperlipidemia, hyperuricemia, and lactic acidemia. Two efficacious recombinant adeno-associated virus pseudotype 2/8 (rAAV8) vectors expressing human G6Pase-alpha have been independently developed. One is a single-stranded vector containing a 2864-bp of the G6PC promoter/enhancer (rAAV8-GPE) and the other is a double-stranded vector containing a shorter 382-bp minimal G6PC promoter/enhancer (rAAV8-miGPE). To identify the best construct, a direct comparison of the rAAV8-GPE and the rAAV8-miGPE vectors was initiated to determine the best vector to take forward into clinical trials. We show that the rAAV8-GPE vector directed significantly higher levels of hepatic G6Pase-alpha expression, achieved greater reduction in hepatic glycogen accumulation, and led to a better toleration of fasting in GSD-Ia mice than the rAAV8-miGPE vector. Our results indicated that additional control elements in the rAAV8-GPE vector outweigh the gains from the double-stranded rAAV8-miGPE transduction efficiency, and that the rAAV8-GPE vector is the current choice for clinical translation in human GSD-Ia. Published by Elsevier Inc.
C1 [Lee, Young Mok; Pan, Chi-Jiunn; Mansfield, Brian C.; Chou, Janice Y.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Cellular Differentiat, Program Dev Endocrinol & Genet, NIH, Bethesda, MD 20892 USA.
[Koeberl, Dwight D.] Duke Univ, Med Ctr, Div Med Genet, Dept Pediat, Durham, NC 27710 USA.
[Mansfield, Brian C.] Fdn Fighting Blindness, Columbia, MD 21046 USA.
RP Chou, JY (reprint author), NIH, Bldg 10,Room 9D42,10 Ctr Dr, Bethesda, MD 20892 USA.
EM chouja@mail.nih.gov
OI Mansfield, Brian/0000-0002-8533-2789
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development, National Institutes of Health; Children's Fund for Glycogen
Storage Disease Research
FX This research was supported by the Intramural Research Program of the
Eunice Kennedy Shriver National Institute of Child Health and Human
Development, National Institutes of Health, and The Children's Fund for
Glycogen Storage Disease Research.
NR 24
TC 6
Z9 6
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 1096-7192
EI 1096-7206
J9 MOL GENET METAB
JI Mol. Genet. Metab.
PD NOV
PY 2013
VL 110
IS 3
BP 275
EP 280
DI 10.1016/j.ymgme.2013.06.014
PG 6
WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research &
Experimental
SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental
Medicine
GA 239WZ
UT WOS:000326058000013
PM 23856420
ER
PT J
AU Mashalidis, EH
Sledz, P
Lang, S
Abell, C
AF Mashalidis, Ellene H.
Sledz, Pawel
Lang, Steffen
Abell, Chris
TI A three-stage biophysical screening cascade for fragment-based drug
discovery
SO NATURE PROTOCOLS
LA English
DT Article
ID ISOTHERMAL TITRATION CALORIMETRY; X-RAY CRYSTALLOGRAPHY; THERMAL SHIFT
ASSAYS; PROTEIN-PROTEIN INTERACTIONS; LEAD DISCOVERY; KINASE INHIBITORS;
NMR-SPECTROSCOPY; LIGAND-BINDING; LIBRARY DESIGN; FLUORESCENCE
AB This protocol describes the screening of a library of low-molecular-weight compounds (fragments) using a series of biophysical ligand-binding assays. Fragment-based drug discovery (FBDD) has emerged as a successful method to design high-affinity ligands for biomacromolecules of therapeutic interest. It involves detecting relatively weak interactions between the fragments and a target macromolecule using sensitive biophysical techniques. These weak binders provide a starting point for the development of inhibitors with submicromolar affinity. Here we describe an efficient fragment screening cascade that can identify binding fragments (hits) within weeks. It is divided into three stages: (i) preliminary screening using differential scanning fluorimetry (DSF), (ii) validation by NMR spectroscopy and (iii) characterization of binding fragments by isothermal titration calorimetry (ITC) and X-ray crystallography. Although this protocol is readily applicable in academic settings because of its emphasis on low cost and medium-throughput early-stage screening technologies, the core principle of orthogonal validation makes it robust enough to meet the quality standards of an industrial laboratory.
C1 [Mashalidis, Ellene H.; Sledz, Pawel; Lang, Steffen; Abell, Chris] Univ Cambridge, Dept Chem, Cambridge CB2 1EW, England.
[Mashalidis, Ellene H.] NIAID, NIH, Bethesda, MD 20892 USA.
RP Abell, C (reprint author), Univ Cambridge, Dept Chem, Lensfield Rd, Cambridge CB2 1EW, England.
EM ca26@cam.ac.uk
FU Gates Cambridge Trust; St. Edmund's College; NIH, NIAID
FX E.H.M. acknowledges the NIH-Cambridge Graduate Partnership Program and
C. Barry (Tuberculosis Research Section, NIAID, NIH). P.S. thanks the
Gates Cambridge Trust and St. Edmund's College for funding. S. L. thanks
the German Academic Exchange Service (DAAD) and the Structural Genomics
Consortium, Oxford. We thank G. Williams (Astex Pharmaceuticals) and all
members of the Abell, Blundell, Hyvonen and Ciulli groups for useful
discussions. This research was supported in part by the Intramural
Research Program of the NIH, NIAID.
NR 62
TC 32
Z9 32
U1 10
U2 73
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1754-2189
EI 1750-2799
J9 NAT PROTOC
JI Nat. Protoc.
PD NOV
PY 2013
VL 8
IS 11
BP 2309
EP 2324
DI 10.1038/nprot.2013.130
PG 16
WC Biochemical Research Methods
SC Biochemistry & Molecular Biology
GA 241JX
UT WOS:000326164100015
PM 24157549
ER
PT J
AU Lazarevic, V
Glimcher, LH
Lord, GM
AF Lazarevic, Vanja
Glimcher, Laurie H.
Lord, Graham M.
TI T-bet: a bridge between innate and adaptive immunity
SO NATURE REVIEWS IMMUNOLOGY
LA English
DT Review
ID CHRONIC VIRAL-INFECTION; IFN-GAMMA PRODUCTION; TRANSCRIPTION FACTOR
EOMESODERMIN; TH1 CELL-DIFFERENTIATION; PATHOGENIC T(H)17 CELLS;
V-ALPHA-14I NKT CELLS; GENE-EXPRESSION; LYMPHOID-CELLS;
INTERFERON-GAMMA; DENDRITIC CELLS
AB Originally described over a decade ago as a T cell transcription factor regulating T helper 1 cell lineage commitment, T-bet is now recognized as having an important role in many cells of the adaptive and innate immune system. T-bet has a fundamental role in coordinating type 1 immune responses by controlling a network of genetic programmes that regulate the development of certain immune cells and the effector functions of others. Many of these transcriptional networks are conserved across innate and adaptive immune cells and these shared mechanisms highlight the biological functions that are regulated by T-bet.
C1 [Lazarevic, Vanja] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA.
[Glimcher, Laurie H.] Weill Cornell Med Coll, New York, NY 10065 USA.
[Lord, Graham M.] Kings Coll London, Dept Expt Immunobiol, London SE1 9RT, England.
RP Glimcher, LH (reprint author), Weill Cornell Med Coll, New York, NY 10065 USA.
EM lglimche@med.cornell.edu
FU US National Institutes of Health [CA112663, PO1NSO38037]; Irvington
Institute; Medical Research Council, UK [G0802068]; Wellcome Trust, UK,
[WT088747MA]; British Heart Foundation, UK [PG/12/36/29444]; National
Institute for Health Research (NIHR) Biomedical Research Centre based at
Guy's and St Thomas' National Health Service (NHS) Foundation Trust and
King's College London, UK
FX We would like to acknowledge support from grants awarded by the US
National Institutes of Health (grants CA112663 and PO1NSO38037) to L. H.
G.; the Irvington Institute to V. L.; and to G. M. L. the Medical
Research Council, UK (grant G0802068), the Wellcome Trust, UK, (grant
WT088747MA) and the British Heart Foundation, UK, (grant
PG/12/36/29444). G. M. L. is also supported by the National Institute
for Health Research (NIHR) Biomedical Research Centre based at Guy's and
St Thomas' National Health Service (NHS) Foundation Trust and King's
College London, UK. The views expressed are those of the authors and not
necessarily those of the NHS, the NIHR or the Department of Health.
NR 107
TC 99
Z9 101
U1 2
U2 42
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 2013
VL 13
IS 11
BP 777
EP 789
DI 10.1038/nri3536
PG 13
WC Immunology
SC Immunology
GA 241HY
UT WOS:000326158400008
PM 24113868
ER
PT J
AU Cocco, P
Vermeulen, R
Flore, V
Nonne, T
Campagna, M
Purdue, M
Blair, A
Monnereau, A
Orsi, L
Clavel, J
Becker, N
de Sanjose, S
Foretova, L
Staines, A
Maynadie, M
Nieters, A
Miligi, L
't Mannetje, A
Kricker, A
Brennan, P
Boffetta, P
Lan, Q
Rothman, N
AF Cocco, P.
Vermeulen, R.
Flore, V.
Nonne, T.
Campagna, M.
Purdue, M.
Blair, A.
Monnereau, A.
Orsi, L.
Clavel, J.
Becker, N.
de Sanjose, S.
Foretova, L.
Staines, A.
Maynadie, M.
Nieters, A.
Miligi, L.
't Mannetje, A.
Kricker, A.
Brennan, P.
Boffetta, P.
Lan, Q.
Rothman, N.
TI Occupational exposure to trichloroethylene and risk of non-Hodgkin
lymphoma and its major subtypes: a pooled IinterLlymph analysis
SO OCCUPATIONAL AND ENVIRONMENTAL MEDICINE
LA English
DT Article
ID EPIDEMIOLOGY CONSORTIUM INTERLYMPH; ORGANIC-SOLVENTS; CANCER INCIDENCE;
WORKERS; METAANALYSIS; MORTALITY; NEOPLASMS; EPILYMPH; COHORT
AB Objectives We evaluated the association between occupational exposure to trichloroethylene (TCE) and risk of non-Hodgkin lymphoma (NHL) in a pooled analysis of four international case-control studies.
Methods Overall, the pooled study population included 3788 NHL cases and 4279 controls. Risk of NHL and its major subtypes associated with TCE exposure was calculated with unconditional logistic regression and polytomous regression analysis, adjusting by age, gender and study.
Results Risk of follicular lymphoma (FL), but not NHL overall or other subtypes, increased by probability (p=0.02) and intensity level (p=0.04), and with the combined analysis of four exposure metrics assumed as independent (p=0.004). After restricting the analysis to the most likely exposed study subjects, risk of NHL overall, FL and chronic lymphocytic leukaemia (CLL) were elevated and increased by duration of exposure (p=0.009, p=0.04 and p=0.01, respectively) and with the combined analysis of duration, frequency and intensity of exposure (p=0.004, p=0.015 and p=0.005, respectively). Although based on small numbers of exposed, risk of all the major NHL subtypes, namely diffuse large B-cell lymphoma, FL and CLL, showed increases in risk ranging 2-3.2-fold in the highest category of exposure intensity. No significant heterogeneity in risk was detected by major NHL subtypes or by study.
Conclusions Our pooled analysis apparently supports the hypothesis of an increase in risk of specific NHL subtypes associated with occupational exposure to TCE.
C1 [Cocco, P.; Flore, V.; Nonne, T.; Campagna, M.] Univ Cagliari, Dept Publ Hlth Clin & Mol Med, Occupat Hlth Sect, Monserrato, Italy.
[Vermeulen, R.] Univ Utrecht, Inst Risk Assessment Sci, Utrecht, Netherlands.
[Purdue, M.; Blair, A.; Lan, Q.; Rothman, N.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Monnereau, A.] Inst Bergonie, Ctr Reg Lutte Canc, Bordeaux, France.
[Orsi, L.; Clavel, J.] INSERM, Villejuif, France.
[Becker, N.] German Canc Res Ctr, Heidelberg, Germany.
[de Sanjose, S.] Catalan Inst Oncol, Canc Epidemiol Res Program, Unit Infect & Canc, Barcelona, Spain.
[de Sanjose, S.] Ctr Invest Biomed Red Epidemiol & Salud Publ CIBE, Barcelona, Spain.
[Foretova, L.] Masaryk Mem Canc Inst, Dept Canc Epidemiol & Genet, Brno, Czech Republic.
[Staines, A.] Dublin City Univ, Sch Nursing & Human Sci, Dublin 9, Ireland.
[Maynadie, M.] Dijon Univ Hosp, Dijon, France.
[Nieters, A.] Univ Freiburg, Ctr Chron Immunodeficiency, D-79106 Freiburg, Germany.
[Miligi, L.] ISPO Canc Prevent & Res Inst, Environm & Occupat Epidemiol Unit, Florence, Italy.
['t Mannetje, A.] Massey Univ, Ctr Publ Hlth Res, Wellington, New Zealand.
[Kricker, A.] Univ Sydney, Sydney Med Sch, Sch Publ Hlth, Sydney, NSW 2006, Australia.
[Brennan, P.] Int Agcy Res Canc, F-69372 Lyon, France.
[Boffetta, P.] Mt Sinai Sch Med, Tisch Canc Inst, New York, NY USA.
RP Cocco, P (reprint author), Univ Cagliari, Dept Publ Hlth Clin & Mol Med, Occupat Hlth Sect, SS 554, I-09042 Cagliari, Italy.
EM coccop@medicina.unica.it
RI de Sanjose Llongueras, Silvia/H-6339-2014; Monnereau, Alain/L-1249-2014;
Campagna, Marcello/L-1011-2016; Clavel, Jacqueline/Q-2750-2016;
Vermeulen, Roel/F-8037-2011
OI Monnereau, Alain/0000-0002-5056-1397; Campagna,
Marcello/0000-0002-5277-8477; Clavel, Jacqueline/0000-0002-3616-7676;
Vermeulen, Roel/0000-0003-4082-8163
FU Italian Ministry for Education, University and Research [2007WEJLZB,
20092ZELR2]; Italian Association for Cancer Research (AIRC) [11855]; US
NIH, National Cancer Institute; Association pour la Recherche contre le
Cancer; Fondation de France; AFSSET; European Commission
[QLK4-CT-2000-00422, FP6-2003-FOOD-2-B, 023103]; Spanish Ministry of
Health [04-0091, RCESP 09-10]; German Federal Office for Radiation
Protection [StSch4261, StSch4420]
FX The study was supported by grants of the Italian Ministry for Education,
University and Research (PRIN 2007 prot. 2007WEJLZB; PRIN 2009 prot.
20092ZELR2); the Italian Association for Cancer Research (AIRC,
Investigator Grant 11855); and the intramural research programme of the
US NIH, National Cancer Institute; the Association pour la Recherche
contre le Cancer; the Fondation de France; AFSSET; a donation from
Faberge employees; the European Commission, 5th Framework Program,
Quality of Life (grant No QLK4-CT-2000-00422); European Commission, 6th
Framework Program, FP6-2003-FOOD-2-B (contract No 023103); the Spanish
Ministry of Health (grant No 04-0091, RCESP 09-10); the German Federal
Office for Radiation Protection (grants No StSch4261 and StSch4420).
NR 35
TC 4
Z9 9
U1 1
U2 12
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 2013
VL 70
IS 11
BP 795
EP 802
DI 10.1136/oemed-2013-101551
PG 8
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 239TN
UT WOS:000326048600009
PM 23881218
ER
PT J
AU Behrens, T
Kendzia, B
Treppmann, T
Olsson, A
Jockel, KH
Gustavsson, P
Pohlabeln, H
Ahrens, W
Bruske, I
Wichmann, HE
Merletti, F
Mirabelli, D
Richiardi, L
Simonato, L
Zaridze, D
Szeszenia-Dabrowska, N
Rudnai, P
Lissowska, J
Fabianova, E
Tardon, A
Field, J
Dumitru, RS
Bencko, V
Foretova, L
Janout, V
Siemiatycki, J
Parent, ME
McLaughlin, J
Demers, P
Landi, MT
Caporaso, N
Kromhout, H
Vermeulen, R
Peters, S
Benhamou, S
Stucker, I
Guida, F
Consonni, D
Bueno-de-Mesquita, B
't Mannetje, A
Pearce, N
Tse, LA
Yu, ITS
Plato, N
Boffetta, P
Straif, K
Schuz, J
Pesch, B
Bruning, T
AF Behrens, Thomas
Kendzia, Benjamin
Treppmann, Tabea
Olsson, Ann
Joeckel, Karl-Heinz
Gustavsson, Per
Pohlabeln, Hermann
Ahrens, Wolfgang
Brueske, Irene
Wichmann, Hans-Erich
Merletti, Franco
Mirabelli, Dario
Richiardi, Lorenzo
Simonato, Lorenzo
Zaridze, David
Szeszenia-Dabrowska, Neonila
Rudnai, Peter
Lissowska, Jolanta
Fabianova, Eleonora
Tardon, Adonina
Field, John
Dumitru, Rodica Stanescu
Bencko, Vladimir
Foretova, Lenka
Janout, Vladimir
Siemiatycki, Jack
Parent, Marie-Elise
McLaughlin, John
Demers, Paul
Landi, Maria Teresa
Caporaso, Neil
Kromhout, Hans
Vermeulen, Roel
Peters, Susan
Benhamou, Simone
Stuecker, Isabelle
Guida, Florence
Consonni, Dario
Bueno-de-Mesquita, Bas
't Mannetje, Andrea
Pearce, Neil
Tse, Lap Ah
Yu, Ignatius Tak-sun
Plato, Nils
Boffetta, Paolo
Straif, Kurt
Schuez, Joachim
Pesch, Beate
Bruening, Thomas
TI Lung cancer risk among bakers, pastry cooks and confectionary makers:
the SYNERGY study
SO OCCUPATIONAL AND ENVIRONMENTAL MEDICINE
LA English
DT Article
ID OCCUPATION; CARCINOGENS; EXPOSURE; MEN
AB Introduction Some studies have suggested increased lung cancer risks among bakers, however the results overall were inconsistent. The authors studied lung cancer risks among bakers and baking-related occupations in the SYNERGY pooled case-control database from 16 countries.
Methods Occupation in a baking-related job was identified from the subjects' job histories. ORs adjusted for log(age), study centre, smoking behaviour and ever employment in a job with known exposure to occupational lung carcinogens were calculated by unconditional logistic regression. Findings were stratified by sex, histological subtype of lung cancer and smoking status.
Results 19366 cases (15606 men) and 23670 control subjects (18528 men) were included. 473 cases (415 men, 58 women) and 501 controls (437 men, 64 women) had ever worked in baking or a related job. We did not observe an increased risk for men in baking (OR 1.01; 95% CI 0.86 to 1.18). No linear trends were observed for duration of employment. Some results suggested increased lung cancer risks for women, for example, for working as a baker for >30years and in never-smokers, but after exclusion of one study these increased risks disappeared.
Discussion The findings from this study do not suggest increased lung cancer risks in baking-related professions.
C1 [Behrens, Thomas; Kendzia, Benjamin; Treppmann, Tabea; Pesch, Beate; Bruening, Thomas] Ruhr Univ Bochum, Inst Prevent & Occupat Med, German Social Accid Insurance IPA Inst, D-44789 Bochum, Germany.
[Olsson, Ann; Straif, Kurt; Schuez, Joachim] Int Agcy Res Canc, F-69372 Lyon, France.
[Olsson, Ann; Gustavsson, Per; Plato, Nils] Karolinska Inst, Inst Environm Med, S-10401 Stockholm, Sweden.
[Joeckel, Karl-Heinz] Univ Hosp Essen, Inst Med Informat Biometry & Epidemiol, Essen, Germany.
[Pohlabeln, Hermann; Ahrens, Wolfgang] Leibniz Inst Prevent Res & Epidemiol BIPS GmbH, Bremen, Germany.
[Ahrens, Wolfgang] Univ Bremen, Inst Stat, D-28359 Bremen, Germany.
[Brueske, Irene; Wichmann, Hans-Erich] Helmholtz Zentrum Munchen, Inst Epidemiol 1, Neuherberg, Germany.
[Merletti, Franco; Mirabelli, Dario; Richiardi, Lorenzo] CPO Piemonte, Canc Epidemiol Unit, Turin, Italy.
[Merletti, Franco; Mirabelli, Dario; Richiardi, Lorenzo] Univ Turin, Turin, Italy.
[Simonato, Lorenzo] Univ Padua, Dept Environm Med & Publ Hlth, Padua, Italy.
[Zaridze, David] Russian Canc Res Ctr, Inst Carcinogenesis, Moscow, Russia.
[Szeszenia-Dabrowska, Neonila] Nofer Inst Occupat Med, Lodz, Poland.
[Rudnai, Peter] Natl Inst Environm Hlth, Budapest, Hungary.
[Lissowska, Jolanta] M Sklodowska Curie Canc Ctr, Warsaw, Poland.
[Lissowska, Jolanta] Inst Oncol, Warsaw, Poland.
[Fabianova, Eleonora] Reg Author Publ Hlth, Banska Bystrica, Slovakia.
[Tardon, Adonina] Univ Oviedo Ciber Epidemiol, CIBERESP, Mol Epidemiol Canc Unit, Oviedo, Spain.
[Field, John] Univ Liverpool, Roy Castle Lung Canc Res Programme, Canc Res Ctr, Liverpool L69 3BX, Merseyside, England.
[Dumitru, Rodica Stanescu] Natl Inst Publ Hlth, Bucharest, Romania.
[Bencko, Vladimir] Charles Univ Prague, Inst Hyg & Epidemiol, Fac Med 1, Prague, Czech Republic.
[Foretova, Lenka] Masaryk Mem Canc Inst, Dept Canc Epidemiol & Genet, Brno, Czech Republic.
[Janout, Vladimir] Palacky Univ, Fac Med, CR-77147 Olomouc, Czech Republic.
[Siemiatycki, Jack] Univ Montreal, Hosp Res Ctr CRCHUM, Montreal, PQ, Canada.
[Siemiatycki, Jack] Univ Montreal, Sch Publ Hlth, Montreal, PQ, Canada.
[Parent, Marie-Elise] Univ Quebec, Inst Armand Frappier, INRS, Laval, PQ, Canada.
[McLaughlin, John; Demers, Paul] Occupat Canc Res Ctr, Can Care Ontario, Toronto, ON, Canada.
[Landi, Maria Teresa; Caporaso, Neil] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Kromhout, Hans; Vermeulen, Roel; Peters, Susan] Univ Utrecht, Inst Risk Assessment Sci, Environm Epidemiol Div, Utrecht, Netherlands.
[Peters, Susan] Univ Western Australia, Western Australian Inst Med Res, Perth, WA 6009, Australia.
[Benhamou, Simone] INSERM, U946, Paris, France.
[Stuecker, Isabelle; Guida, Florence] INSERM, Ctr Res Epidemiol & Populat Hlth CESP, U1018, Environm Epidemiol Canc Team, F-94807 Villejuif, France.
[Stuecker, Isabelle; Guida, Florence] Univ Paris Sud, UMRS 1018, F-94807 Villejuif, France.
[Consonni, Dario] Fdn IRCCS Ca Granda Osped Maggiore Policlin, Unit Epidemiol, Milan, Italy.
[Bueno-de-Mesquita, Bas] Natl Inst Publ Hlth & Environm Protect, Ctr Nutr & Hlth, NL-3720 BA Bilthoven, Netherlands.
['t Mannetje, Andrea] Massey Univ, Ctr Publ Hlth Res, Wellington, New Zealand.
[Pearce, Neil] London Sch Hyg & Trop Med, Fac Epidemiol & Populat Hlth, London WC1, England.
[Tse, Lap Ah; Yu, Ignatius Tak-sun] Chinese Univ Hong Kong, Div Occupat & Environm Hlth, JC Sch Publ Hlth & Primary Care, Hong Kong, Hong Kong, Peoples R China.
[Boffetta, Paolo] Mt Sinai Sch Med, Tisch Canc Inst, New York, NY USA.
[Boffetta, Paolo] Int Prevent Res Inst, Lyon, France.
RP Behrens, T (reprint author), Ruhr Univ Bochum, Inst Prevent & Occupat Med, German Social Accid Insurance IPA Inst, Burkle de la Camp Pl 1, D-44789 Bochum, Germany.
EM behrens@ipa-dguv.de; behrens@ipa-dguv.de
RI Bruske, Irene/N-3125-2013; Yu, Ignatius Tak Sun/A-9936-2008; Janout,
Vladimir/M-5133-2014; Szeszenia-Dabrowska, Neonila/F-7190-2010; Bruning,
Thomas/G-8120-2015; Consonni, Dario/K-7943-2016; Vermeulen,
Roel/F-8037-2011;
OI richiardi, lorenzo/0000-0003-0316-9402; Bruning,
Thomas/0000-0001-9560-5464; Consonni, Dario/0000-0002-8935-3843;
Vermeulen, Roel/0000-0003-4082-8163; Peters, Susan/0000-0001-5662-1971;
Pearce, Neil/0000-0002-9938-7852; Lissowska,
Jolanta/0000-0003-2695-5799; Field, John/0000-0003-3951-6365; Ahrens,
Wolfgang/0000-0003-3777-570X
FU German Social Accident Insurance [FP 271]; Canadian Institutes of Health
Research; Guzzo-SRC Chair in Environment and Cancer; Fondation de
France; German Federal Ministry of Education, Science, Research, and
Technology; Ministry of Labour and Social Affairs; EC's INCO-COPERNICUS
Program; Polish State Committee for Science Research; Roy Castle
Foundation; NIH/NCI/DCEG Intramural Research Program, Lombardy Region;
INAIL; European Union Nuclear Fission Safety Program; Italian
Association for Cancer Research; Region Piedmont; Compagnia di San
Paolo; Europe Against Cancer Program; Swedish Council for Work Life
Research; Swedish EPA; University of Oviedo; European Regional
Development Fund; State Budget of the Czech Republic (RECAMO)
[CZ.1.05/2.1.00/03.0101]; CIBERESP; [FISS-PI060604]
FX This study was supported by the German Social Accident Insurance, grant
FP 271. Grant sponsors of the individual studies were the Canadian
Institutes of Health Research and Guzzo-SRC Chair in Environment and
Cancer, the Fondation de France, the German Federal Ministry of
Education, Science, Research, and Technology and the Ministry of Labour
and Social Affairs, the EC's INCO-COPERNICUS Program, the Polish State
Committee for Science Research, the Roy Castle Foundation, the
NIH/NCI/DCEG Intramural Research Program, Lombardy Region, INAIL and the
European Union Nuclear Fission Safety Program, the Italian Association
for Cancer Research, Region Piedmont, the Compagnia di San Paolo, the
Europe Against Cancer Program, the Swedish Council for Work Life
Research and the Swedish EPA, the University of Oviedo, the European
Regional Development Fund and the State Budget of the Czech Republic
(RECAMO, CZ.1.05/2.1.00/03.0101), CIBERESP and FISS-PI060604.
NR 15
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U1 1
U2 13
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 2013
VL 70
IS 11
BP 810
EP 814
DI 10.1136/oemed-2013-101469
PG 5
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 239TN
UT WOS:000326048600011
PM 23911873
ER
PT J
AU Wu, YW
Hess, CP
Singhal, NS
Groden, C
Toro, C
AF Wu, Yvonne W.
Hess, Christopher P.
Singhal, Nilika S.
Groden, Catherine
Toro, Camila
TI Idiopathic Basal Ganglia Calcifications: An Atypical Presentation of
PKAN
SO PEDIATRIC NEUROLOGY
LA English
DT Article
DE basal ganglia; calcification; neurodegeneration; genetics; dystonia;
Fahr disease; eye of the tiger; PANK2; PKAN; pantothenate kinase
ID KINASE-ASSOCIATED NEURODEGENERATION; HALLERVORDEN-SPATZ-SYNDROME;
THE-TIGER SIGN; PANK2 MUTATIONS; EYE; DISEASE
AB BACKGROUND: We report a patient with pantothenate kinase associated neurodegeneration presenting as idiopathic basal ganglia calcifications, previously known as Fahr's disease. METHODS: A teenage girl presented with slowly progressive dystonia. Her brain magnetic resonance imaging scan revealed TI and T2 hypointensities in both globus pallidi, and no eye-of-the-tiger sign. Computed tomography showed dense globus pallidi calcifications. Metabolic evaluation was negative. The patient was diagnosed with idiopathic basal ganglia calcifications, a poorly understood syndrome of unknown cause. Whole exome sequencing was performed. RESULTS: The patient was found to have two mutations in the pantothenate kinase 2 (PANK2) gene that have been previously associated with pantothenate kinase associated neurodegeneration: a paternally inherited p.G521R and maternally inherited p.T528M. No deleterious changes were identified in genes associated with idiopathic basal ganglia calcifications or dystonia. CONCLUSIONS: Pantothenate kinase associated neurodegeneration should be considered in patients with idiopathic basal ganglia calcifications, especially when findings are confined to the globus pallidus.
C1 [Wu, Yvonne W.; Singhal, Nilika S.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA.
[Wu, Yvonne W.] Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA.
[Hess, Christopher P.] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94143 USA.
[Groden, Catherine; Toro, Camila] NHGRI, NIH, Undiagnosed Dis Program, Bethesda, MD 20892 USA.
RP Wu, YW (reprint author), Univ Calif San Francisco, Dept Neurol, 350 Parnassus,Suite 609, San Francisco, CA 94143 USA.
EM wuy@neuropeds.ucsf.edu
OI Hess, Christopher/0000-0002-5132-5302
FU earch Program of the National Human Genome Research Institute and the
National Institutes of Health (NIH) Common Fund [1R01 FD004103-01]
FX Portions of this work were funded by the Intramural Research Program of
the National Human Genome Research Institute and the National Institutes
of Health (NIH) Common Fund (NIH Undiagnosed Diseases Program). Dr. Hess
is a co-investigator on NIH 1R01 FD004103-01 Phase 2 Study of
Deferiprone in the Treatment of NBIA.
NR 15
TC 8
Z9 9
U1 0
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0887-8994
EI 1873-5150
J9 PEDIATR NEUROL
JI Pediatr. Neurol.
PD NOV
PY 2013
VL 49
IS 5
BP 351
EP 354
DI 10.1016/j.pediatrneurol.2013.06.021
PG 4
WC Clinical Neurology; Pediatrics
SC Neurosciences & Neurology; Pediatrics
GA 242BK
UT WOS:000326212200011
PM 23968566
ER
PT J
AU Imayama, I
Alfano, CM
Mason, C
Wang, CC
Duggan, C
Campbell, KL
Kong, A
Foster-Schubert, KE
Blackburn, GL
Wang, CY
McTiernan, A
AF Imayama, Ikuyo
Alfano, Catherine M.
Mason, Caitlin
Wang, Chiachi
Duggan, Catherine
Campbell, Kristin L.
Kong, Angela
Foster-Schubert, Karen E.
Blackburn, George L.
Wang, Ching-Yun
McTiernan, Anne
TI Weight and metabolic effects of dietary weight loss and exercise
interventions in postmenopausal antidepressant medication users and
non-users: A randomized controlled trial
SO PREVENTIVE MEDICINE
LA English
DT Article
DE Obesity; Weight loss intervention; Antidepressants; Diet; Exercise
ID DIABETES PREVENTION PROGRAM; BINGE-EATING DISORDER; INSULIN-RESISTANCE;
CARDIOVASCULAR-DISEASE; PHYSICAL-ACTIVITIES; MAJOR DEPRESSION; MEDICINE
USE; WOMEN; RISK; HEALTH
AB Objective. Antidepressants may attenuate the effects of diet and exercise programs. We compared adherence and changes in body measures and biomarkers of glucose metabolism and inflammation between antidepressant users and non-users in a 12-month randomized controlled trial.
Methods. Overweight or obese, postmenopausal women were assigned to: diet (10% weight loss goal, N = 118); moderate-to-vigorous aerobic exercise (225 min/week, N = 117); diet + exercise (N = 117); and control (N = 87) in Seattle, WA 2005-2009. Women using antidepressants at baseline were classified as users (N = 109). ANCOVA and generalized estimating equation approaches, respectively, were used to compare adherence (exercise amount, diet session attendance, and changes in percent calorie intake from fat, cardiopulmonary fitness, and pedometer steps) and changes in body measures (weight, waist and percent body fat) and serum biomarkers (glucose, insulin, homeostasis assessment-insulin resistance, and high-sensitivity C-reactive protein) between users and non-users. An interaction term (intervention x antidepressant use) tested effect modification.
Results. There were no differences in adherence except that diet session attendance was lower among users in the diet + exercise group (P < 0.05 vs. non-users). Changes in body measures and serum biomarkers did not differ by antidepressant use (Pinteraction > 0.05).
Conclusion. Dietary weight loss and exercise improved body measures and biomarkers of glucose metabolism and inflammation independent of antidepressant use. (C) 2013 Elsevier Inc. All rights reserved.
C1 [Imayama, Ikuyo; Mason, Caitlin; Wang, Chiachi; Duggan, Catherine; McTiernan, Anne] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Program Epidemiol, Seattle, WA 98104 USA.
[Alfano, Catherine M.] NCI, Off Canc Survivorship, NIH, Bethesda, MD 20892 USA.
[Campbell, Kristin L.] Univ British Columbia, Fac Med, Vancouver, BC, Canada.
[Kong, Angela] Univ Illinois, Canc Educ & Career Dev Program, Chicago, IL USA.
[Foster-Schubert, Karen E.; McTiernan, Anne] Univ Washington, Sch Med, Seattle, WA USA.
[Blackburn, George L.] Harvard Univ, Sch Med, Div Nutr, Boston, MA USA.
[Wang, Ching-Yun; McTiernan, Anne] Univ Washington, Sch Publ Hlth, Seattle, WA 98195 USA.
[Wang, Ching-Yun] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA.
RP McTiernan, A (reprint author), Fred Hutchinson Canc Res Ctr, 1100 Fairview Ave N,M4-B874,POB 19024, Seattle, WA USA.
EM amctiern@fhcrc.org
RI Duggan, Catherine/F-9414-2015
OI Duggan, Catherine/0000-0001-7369-4021
FU National Cancer Institute (NCI) [R01 CA105204-01A1, U54-CA116847];
National Institute of Diabetes and Digestive and Kidney Disease (NIDDK)
[61-7015]; Canadian Institutes of Health Research; NCI [R25CA094880,
2R25CA057699]; National Center for Research Resources [5KL2RR025015-03]
FX The NEW trial was supported by R01 CA105204-01A1 and U54-CA116847 from
the National Cancer Institute (NCI). Part of this study was conducted at
the University of Washington, Clinical Nutrition Research Unit supported
by the National Institute of Diabetes and Digestive and Kidney Disease
(NIDDK) 61-7015. While working on the trial, CMA was employed at the
Ohio State University, and located to NCI following completion of her
effort on the NEW trial. CM is and KC was supported by a fellowship from
the Canadian Institutes of Health Research. AK was supported by NCI
R25CA094880 at the time of this study and is currently supported by NCI
2R25CA057699. KEF is supported by 5KL2RR025015-03 from the National
Center for Research Resources, a component of the National Institute of
Health (NIH) and NIH Roadmap for Medical Research. These funding
agencies had no role in the study design, data collection, data analysis
and interpretation of the results, and writing of the article and
decision to submit it for publication.
NR 40
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U2 16
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 2013
VL 57
IS 5
BP 525
EP 532
DI 10.1016/j.ypmed.2013.07.006
PG 8
WC Public, Environmental & Occupational Health; Medicine, General &
Internal
SC Public, Environmental & Occupational Health; General & Internal Medicine
GA 239WV
UT WOS:000326057600022
PM 23859929
ER
PT J
AU Taber, DR
Chriqui, JF
Perna, FM
Powell, LM
Slater, SJ
Chaloupka, FJ
AF Taber, Daniel R.
Chriqui, Jamie F.
Perna, Frank M.
Powell, Lisa M.
Slater, Sandy J.
Chaloupka, Frank J.
TI Association between state physical education (PE) requirements and PE
participation, physical activity, and body mass index change
SO PREVENTIVE MEDICINE
LA English
DT Article
DE Physical education; Exercise; Nutrition; Obesity; Adolescent; Health
policy; Schools
ID CHILDREN; OBESITY; ADOLESCENTS; POLICIES; SCHOOLS; TRENDS; OVERWEIGHT;
HEALTH; IMPACT; YOUTH
AB Objective. To determine if state physical education (PE) laws are associated with student physical education attendance and physical activity (PA), and whether physical education and competitive food laws, in conjunction, are associated with lower BMI change.
Method State laws regarding physical education time requirements and competitive foods in 2003 and 2006 were classified as strong, weak, or none, based on codified law ratings obtained from the Classification of Laws Associated with School Students. Laws were linked to student data on PE attendance and physical activity (8th grade, Spring 2007) and BMI change (5th-8th grade, 2004-2007), obtained from the Early Childhood Longitudinal Study (n = 5510 students in 40 states).
Results. Girls reported 0.31 more days of activity (95% CI: 0.02, 0.61) and were more likely to attend physical education >= 3 days/week (74.1% versus 52.1%, difference = 22.0,95% CI: 2.1, 42.0) if they resided in states with strong physical education laws compared to no physical education laws. Weak physical education laws had modest associations with PE and activity, and there was no evidence that weak laws reduce BMI gain regardless of competitive food laws.
Conclusion. Strong physical education laws with specific time requirements may increase physical education attendance and activity in girls. There is insufficient evidence that physical education laws reduce student weight gain. (C) 2013 Elsevier Inc. All rights reserved.
C1 [Taber, Daniel R.; Chriqui, Jamie F.; Powell, Lisa M.; Slater, Sandy J.; Chaloupka, Frank J.] Univ Illinois, Inst Hlth Res & Policy, Chicago, IL 60608 USA.
[Chriqui, Jamie F.] Univ Illinois, Dept Polit Sci, Chicago, IL 60607 USA.
[Perna, Frank M.] Natl Canc Inst, Div Canc Control & Populat Sci, Rockville, MD 20850 USA.
[Powell, Lisa M.; Slater, Sandy J.] Univ Illinois, Dept Hlth Policy & Adm, Chicago, IL 60612 USA.
[Chaloupka, Frank J.] Univ Illinois, Dept Econ, Chicago, IL 60607 USA.
RP Taber, DR (reprint author), Univ Texas Austin, Sch Publ Hlth, Austin Reg Campus,1616 Guadalupe,Suite 6-300, Austin, TX 78701 USA.
EM Daniel.Taber@uth.tmc.edu; jchriqui@uic.edu; pernafm@mail.nih.gov;
powelll@uic.edu; sslater@uic.edu; fjc@uic.edu
FU Robert Wood Johnson Foundation; National Cancer Institute
[HHSN261201000350P, HHSN261201100522P]
FX Support for this study was provided by the Robert Wood Johnson
Foundation to the Bridging the Gap Program at the University of Illinois
at Chicago (PI: Frank Chaloupka) and contracts HHSN261201000350P and
HHSN261201100522P from the National Cancer Institute to the University
of Illinois at Chicago (PI: Jamie Chriqui). The views expressed herein
are solely those of the authors and do not reflect the official views or
positions of the Robert Wood Johnson Foundation; the National Cancer
Institute; or the National Institutes of Health.
NR 42
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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 2013
VL 57
IS 5
BP 629
EP 633
DI 10.1016/j.ypmed.2013.08.018
PG 5
WC Public, Environmental & Occupational Health; Medicine, General &
Internal
SC Public, Environmental & Occupational Health; General & Internal Medicine
GA 239WV
UT WOS:000326057600040
PM 23978523
ER
PT J
AU Mazor, KM
Beard, RL
Alexander, GL
Arora, NK
Firneno, C
Gaglio, B
Greene, SM
Lemay, CA
Robinson, BE
Roblin, DW
Walsh, K
Street, RL
Gallagher, TH
AF Mazor, Kathleen M.
Beard, Renee L.
Alexander, Gwen L.
Arora, Neeraj K.
Firneno, Cassandra
Gaglio, Bridget
Greene, Sarah M.
Lemay, Celeste A.
Robinson, Brandi E.
Roblin, Douglas W.
Walsh, Kathleen
Street, Richard L., Jr.
Gallagher, Thomas H.
TI Patients' and family members' views on patient-centered communication
during cancer care
SO PSYCHO-ONCOLOGY
LA English
DT Article
DE cancer; oncology; patient-centered communication; qualitative;
interviews
ID PHYSICIAN COMMUNICATION; PERSPECTIVES; PERCEPTIONS; QUALITY; TIME
AB ObjectivesTo explore patients' and family members' views on communication during cancer care and to identify those aspects of clinician-patient communication which were most important to patients and family members.
MethodsWe conducted a secondary data analysis of qualitative data from 137 patients with cancer and family members of patients with cancer. We used a modified version of the constant comparative method and coding paradigm of grounded theory.
ResultsPatients want sensitive, caring clinicians who provide information that they need, when they need it, in a way that they can understand; who listen and respond to questions and concerns, and who attempt to understand the patient's experience. Effective information exchange and a positive interpersonal relationship with the clinician were of fundamental importance to patients and family members. These were interrelated; for instance, failure to provide information a patient needed could damage the relationship, whereas excellent listening could foster the relationship. Information exchange and relationship were also integral to decision-making, managing uncertainty, responding to emotions, and self-management. Clinicians who were responsive to patients' needs beyond the immediate medical encounter were valued.
ConclusionsThe complexity of cancer care today suggests that efforts to improve communication must be multilevel, acknowledging and addressing patient, clinician, organizational and policy barriers, and facilitators. Measurement tools are needed to assess cancer patients' and family members' experiences with communication over the course of cancer care to provide meaningful, actionable feedback to those seeking to optimize their effectiveness in communicating with patients with cancer. Copyright (c) 2013 John Wiley & Sons, Ltd.
C1 [Mazor, Kathleen M.; Firneno, Cassandra; Lemay, Celeste A.] Univ Massachusetts, Sch Med, Meyers Primary Care Inst, Reliant Med Grp,Fallon Community Hlth Plan, Worcester, MA 01605 USA.
[Beard, Renee L.] Coll Holy Cross, Dept Sociol & Anthropol, Worcester, MA 01610 USA.
[Alexander, Gwen L.] Henry Ford Hlth Syst, Dept Publ Hlth Sci, Detroit, MI USA.
[Arora, Neeraj K.] NCI, Div Canc Control & Populat Sci, Rockville, MD USA.
[Gaglio, Bridget] Kaiser Permanente Midatlantic States, Res Inst, Midatlantic Permanente, Rockville, MD USA.
[Greene, Sarah M.] Grp Hlth Cooperat Puget Sound, Seattle, WA USA.
[Robinson, Brandi E.; Roblin, Douglas W.] Kaiser Permanente Georgia, Ctr Hlth Res, Atlanta, GA USA.
[Walsh, Kathleen] Univ Massachusetts, Sch Med, Dept Pediat, Worcester, MA USA.
[Walsh, Kathleen] Meyers Primary Care Inst, Worcester, MA USA.
[Street, Richard L., Jr.] Texas A&M Univ, Dept Commun, College Stn, TX USA.
[Gallagher, Thomas H.] Univ Washington, Seattle, WA 98195 USA.
RP Mazor, KM (reprint author), Univ Massachusetts, Sch Med, Meyers Primary Care Inst, Reliant Med Grp,Fallon Community Hlth Plan, Worcester, MA 01605 USA.
EM kathy.mazor@meyersprimary.org
FU National Cancer Institute [P20CA137219, U19 CA79689]; HMO CRN pilot
grant; University of Massachusetts Clinical and Translational Science
Cente; National Center for Advancing Translational Sciences
[8UL1TR000161]
FX This study was conducted in the Cancer Communication Research Center,
funded by the National Cancer Institute (P20CA137219). Original data
collection was funded by this grant, and by a supplement (P20CA137219),
by an HMO CRN pilot grant, also funded by the National Cancer Institute
(U19 CA79689) and via funding from the University of Massachusetts
Clinical and Translational Science Center, which is funded by the
National Center for Advancing Translational Sciences (8UL1TR000161).
NR 22
TC 21
Z9 21
U1 1
U2 22
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1057-9249
EI 1099-1611
J9 PSYCHO-ONCOLOGY
JI Psycho-Oncol.
PD NOV
PY 2013
VL 22
IS 11
BP 2487
EP 2495
DI 10.1002/pon.3317
PG 9
WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences,
Biomedical
SC Oncology; Psychology; Biomedical Social Sciences
GA 239MS
UT WOS:000326030300011
PM 23780672
ER
PT J
AU Erdmann, RB
Gartner, JG
Leonard, WJ
Ellison, CA
AF Erdmann, R. B.
Gartner, J. G.
Leonard, W. J.
Ellison, C. A.
TI Lack of Functional TSLP Receptors Mitigates Th2 Polarization and the
Establishment and Growth of 4T1 Primary Breast Tumours but has Different
Effects on Tumour Quantities in the Lung and Brain
SO SCANDINAVIAN JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID THYMIC STROMAL LYMPHOPOIETIN; IGM(+) B-CELLS; CD4(+) T-CELLS; AIRWAY
INFLAMMATION; IN-VITRO; CANCER PROGRESSION; DENDRITIC CELLS; EXPRESSION;
BARRIER; MICE
AB The 4T1 mammary carcinoma cell line produces TSLP. We had hypothesized that TSLP promotes the development of a permissive environment for the growth and metastasis of primary tumour and that this is associated with a Th2-polarized antitumour immune response. We found that, in Tslpr(-/-) mice, the mean tumour diameters were smaller from days 27 to 40, and relatively fewer tumour cells were present in the lung, compared with wild-type mice. Polarization of the Th2 cytokine profile was also diminished in Tslpr(-/-) mice. These findings confirmed those reported previously by others. Here, we further show that primary tumours are established less often in Tslpr(-/-) mice and that, unexpectedly, the relative number of tumour cells in the brain is greater in Tslpr(-/-) mice compared with wild-type mice. Findings from our cytotoxicity assays show that 4T1-directed lysis is undetectable in both WT and Tslpr(-/-) mice, ruling out the possibility that altered cytotoxic responses in Tslpr(-/-) mice are responsible for the differences we observed. In a human tissue microarray, positive staining for TSLP was seen in tumour cells from breast cancer tissue, but it was also seen in normal glandular epithelial cells from normal breast tissue, which has not been shown before. Thus, our findings provide new insight into the effects of TSLP in metastatic breast cancer.
C1 [Erdmann, R. B.; Gartner, J. G.; Ellison, C. A.] Univ Manitoba, Dept Immunol, Fac Med, Winnipeg, MB R3E 3P5, Canada.
[Gartner, J. G.; Ellison, C. A.] Univ Manitoba, Dept Pathol, Fac Med, Winnipeg, MB R3E 3P5, Canada.
[Leonard, W. J.] NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA.
RP Ellison, CA (reprint author), Univ Manitoba, Dept Pathol, Fac Med, 401 Brodie Ctr,727 McDermot Ave, Winnipeg, MB R3E 3P5, Canada.
EM Cynthia.Ellison@med.umanitoba.ca
FU CancerCare Manitoba Foundation
FX This project was funded by an operating grant awarded to C. A. Ellison
by the CancerCare Manitoba Foundation. We thank Ms. Sandra Troup and
Michelle Parisien from the Manitoba Breast Tumor Bank for their expert
assistance with the TMA experiments. We also thank Dr. John Wilkins for
the use of his microplate reader in the chemiluminescence assays.
NR 46
TC 7
Z9 8
U1 0
U2 3
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0300-9475
EI 1365-3083
J9 SCAND J IMMUNOL
JI Scand. J. Immunol.
PD NOV
PY 2013
VL 78
IS 5
BP 408
EP 418
DI 10.1111/sji.12106
PG 11
WC Immunology
SC Immunology
GA 240EL
UT WOS:000326077600003
PM 24033709
ER
PT J
AU Wurtz, RH
AF Wurtz, Robert H.
TI David H. Hubel (1926-2013)
SO SCIENCE
LA English
DT Biographical-Item
C1 NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA.
RP Wurtz, RH (reprint author), NEI, Sensorimotor Res Lab, NIH, 49 Convent Dr, Bethesda, MD 20892 USA.
EM bob@lsr.nei.nih.gov
NR 0
TC 0
Z9 0
U1 0
U2 2
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 0036-8075
EI 1095-9203
J9 SCIENCE
JI Science
PD NOV 1
PY 2013
VL 342
IS 6158
BP 572
EP 572
DI 10.1126/science.1247113
PG 1
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 243RJ
UT WOS:000326334300030
PM 24179213
ER
PT J
AU McLellan, JS
Chen, M
Joyce, MG
Sastry, M
Stewart-Jones, GBE
Yang, YP
Zhang, BS
Chen, L
Srivatsan, S
Zheng, AQ
Zhou, TQ
Graepel, KW
Kumar, A
Moin, S
Boyington, JC
Chuang, GY
Soto, C
Baxa, U
Bakker, AQ
Spits, H
Beaumont, T
Zheng, ZZ
Xia, NS
Ko, SY
Todd, JP
Rao, S
Graham, BS
Kwong, PD
AF McLellan, Jason S.
Chen, Man
Joyce, M. Gordon
Sastry, Mallika
Stewart-Jones, Guillaume B. E.
Yang, Yongping
Zhang, Baoshan
Chen, Lei
Srivatsan, Sanjay
Zheng, Anqi
Zhou, Tongqing
Graepel, Kevin W.
Kumar, Azad
Moin, Syed
Boyington, Jeffrey C.
Chuang, Gwo-Yu
Soto, Cinque
Baxa, Ulrich
Bakker, Arjen Q.
Spits, Hergen
Beaumont, Tim
Zheng, Zizheng
Xia, Ningshao
Ko, Sung-Youl
Todd, John-Paul
Rao, Srinivas
Graham, Barney S.
Kwong, Peter D.
TI Structure-Based Design of a Fusion Glycoprotein Vaccine for Respiratory
Syncytial Virus
SO SCIENCE
LA English
DT Article
ID B-CELL RECEPTORS; MONOCLONAL-ANTIBODY; NEUTRALIZING ANTIBODY; PROTEIN;
EPITOPE; MOTAVIZUMAB; SCAFFOLD; GP120
AB Respiratory syncytial virus (RSV) is the leading cause of hospitalization for children under 5 years of age. We sought to engineer a viral antigen that provides greater protection than currently available vaccines and focused on antigenic site empty set, a metastable site specific to the prefusion state of the RSV fusion (F) glycoprotein, as this site is targeted by extremely potent RSV-neutralizing antibodies. Structure-based design yielded stabilized versions of RSV F that maintained antigenic site empty set when exposed to extremes of pH, osmolality, and temperature. Six RSV F crystal structures provided atomic-level data on how introduced cysteine residues and filled hydrophobic cavities improved stability. Immunization with site empty set-stabilized variants of RSV F in mice and macaques elicited levels of RSV-specific neutralizing activity many times the protective threshold.
C1 [McLellan, Jason S.; Chen, Man; Joyce, M. Gordon; Sastry, Mallika; Stewart-Jones, Guillaume B. E.; Yang, Yongping; Zhang, Baoshan; Chen, Lei; Srivatsan, Sanjay; Zheng, Anqi; Zhou, Tongqing; Graepel, Kevin W.; Kumar, Azad; Moin, Syed; Boyington, Jeffrey C.; Chuang, Gwo-Yu; Soto, Cinque; Ko, Sung-Youl; Todd, John-Paul; Rao, Srinivas; Graham, Barney S.; Kwong, Peter D.] NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
[Baxa, Ulrich] SAIC Frederick Inc, Electron Microscope Lab, Adv Technol Program, Frederick Natl Lab Canc Res, Frederick, MD 21702 USA.
[Bakker, Arjen Q.; Spits, Hergen; Beaumont, Tim] AIMM Therapeut, Acad Med Ctr, NL-1105 BA Amsterdam, Netherlands.
[Zheng, Zizheng; Xia, Ningshao] Xiamen Univ, Natl Inst Diagnost & Vaccine Dev Infect Dis, Xiamen 361005, Peoples R China.
RP Graham, BS (reprint author), NIAID, Vaccine Res Ctr, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM bgraham@nih.gov; pdkwong@nih.gov
RI Zhou, Tongqing/A-6880-2010
OI Zhou, Tongqing/0000-0002-3935-4637
FU National Institute of Allergy and Infectious Diseases; National Natural
Science Foundation of China [81161120419, 812111615]; U.S. Department of
Energy, Basic Energy Sciences, Office of Science [W-31-109-Eng-38]
FX We thank A. M. Salazar for poly-ICLC; J. Stuckey for assistance with
figures; I. S. Georgiev and M. Pancera for assistance with immunogen
design; G. J. Nabel, R. A. Seder, L. Shapiro, and members of the
Structural Biology Section; Structural Bioinformatics Core Section; and
Viral Pathogenesis Laboratory at the Vaccine Research Center for helpful
comments; and J. Chrzas, J. Gonczy, U. Chinte, and staff at SER-CAT
(Southeast Regional Collaborative Access Team) for help with x-ray
diffraction data collection. The data presented in this manuscript are
tabulated in the main paper and supplementary materials. Atomic
coordinates and structure factors of the reported crystal structures
have been deposited in the Protein Data Bank under accession codes 4MMQ
to 4MMV. Support for this work was provided by the Intramural Research
Program (National Institute of Allergy and Infectious Diseases) and the
National Natural Science Foundation of China (81161120419 and
812111615). Use of insertion device 22 (SER-CAT) at the Advanced Photon
Source was supported by the U.S. Department of Energy, Basic Energy
Sciences, Office of Science, under contract W-31-109-Eng-38. H. S. and
T. B. are inventors on an international patent application describing
the technology used to isolate D25 and AM22 (Means and methods for
influencing the stability of antibody producing cells, WO2007067046A1).
A. Q. B. and T. B. are inventors on international patent applications
for antibody D25 (RSV-specific binding molecules and means for producing
them, WO2008147196A2) and antibody AM22 (RSV-specific binding molecule,
WO2011043643A1). J. S. M., M. G. J., B.Z., B. S. G., and P. D. K. are
inventors on U. S. patent applications describing the use of
prefusion-stabilized RSV F glycoproteins as vaccine antigens (Prefusion
RSV F proteins and their use, 61/798,389 and 61/863,909). J. S. M., M.
C., Z.Z., N.X., and B. S. G. are inventors on a Chinese patent
application for antibody 5C4 and its epitope (Anti-RSV high
neutralization antibody and the peptide can be used for prevention of
RSV infection and related disease, 201310082338.1). Reagents from the
NIH are subject to nonrestrictive materials transfer agreements.
NR 33
TC 167
Z9 173
U1 37
U2 103
PU AMER ASSOC ADVANCEMENT SCIENCE
PI WASHINGTON
PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA
SN 0036-8075
EI 1095-9203
J9 SCIENCE
JI Science
PD NOV 1
PY 2013
VL 342
IS 6158
BP 592
EP 598
DI 10.1126/science.1243283
PG 7
WC Multidisciplinary Sciences
SC Science & Technology - Other Topics
GA 243RJ
UT WOS:000326334300041
PM 24179220
ER
PT J
AU Taieb, D
Varoquaux, A
Chen, CC
Pacak, K
AF Taieeb, David
Varoquaux, Arthur
Chen, Clara C.
Pacak, Karel
TI Current and Future Trends in the Anatomical and Functional Imaging of
Head and Neck Paragangliomas
SO SEMINARS IN NUCLEAR MEDICINE
LA English
DT Review
ID POSITRON-EMISSION-TOMOGRAPHY; GLOMUS-JUGULARE TUMORS; SOMATOSTATIN
RECEPTOR SUBTYPE-2; GAMMA-KNIFE RADIOSURGERY; GERMLINE MUTATIONS;
SUCCINATE-DEHYDROGENASE; IN-111-PENTETREOTIDE SCINTIGRAPHY; OCTREOTIDE
SCINTIGRAPHY; I-123-MIBG SPECT; MR-ANGIOGRAPHY
AB Head and neck paragangliomas (HNPGLs) account for approximately 3% of all paragangliomas (PGLs). Most often, HNPGLs are benign, nonsecreting, and slowly progressing. The initial physical examination and biochemical diagnosis usually adds very little to the proper diagnosis of these tumors, and, therefore, radiologists and nuclear medicine physicians play a pivotal role in providing the initial diagnosis, the locoregional staging, and the plan for detecting potential multicentric or metastatic lesions. Based on several current studies, the most accurate use of HNPGL-specific initial and subsequent imaging modalities must be guided by the knowledge of genetics and the specifically measured biochemical profile of these tumors for the proper management of these patients. Thus, this short review article presents the application of the most up-to-date anatomical and functional imaging approaches to HNPGLs tightly linked to the clinical management of these patients. Based on the most recent studies, 18F-FDOPA PET/CT has been shown to be a useful addition to anatomical imaging in the preoperative localization and molecular assessment of HNPGLs. It is estimated that the frequency of metabolically active PGLs on 18F-FDOPA PET/CT in this region is higher than 90%. For patients with hereditary PGL syndromes, F-18-FDG-PET/CT should be reserved. Imaging of somatostatin receptors using Octreoscan or 68Ga-labeled somatostatin analogues plays an important role for selecting patients for targeted radiation therapy. This review also concludes that it is expected that in the near future, these patients will indeed benefit from new diagnostic approaches based on the identification of new targets by molecular profiling studies that will result in the development of novel PGL-specific radiopharamceuticals. Published by Elsevier Inc.
C1 [Taieeb, David] Aix Marseille Univ, La Timone Univ Hosp, CERIMED, Dept Nucl Med, Marseille, France.
[Varoquaux, Arthur] Aix Marseille Univ, La Timone Univ Hosp, Dept Radiol, Marseille, France.
[Chen, Clara C.] NIH, Ctr Clin, Dept Radiol & Imaging Sci, Bethesda, MD 20892 USA.
[Pacak, Karel] NIH, Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, Bethesda, MD 20892 USA.
RP Pacak, K (reprint author), NIH, CRC, Eunice Kennedy Shriver NICHD, Bldg 10,Room 1E-3140,10 Ctr Dr MSC-1109, Bethesda, MD 20892 USA.
EM karel@mail.nih.gov
FU Intramural Research Program of the Eunice Kennedy Shriver National
Institute of Child Health and Human Development; National Institute of
Neurological Disorders and Stroke at the National Institutes of Health
FX The authors would like to thank Victoria Martucci for her excellent
technical assistance in the preparation of this manuscript. This
research was supported by the Intramural Research Program of the Eunice
Kennedy Shriver National Institute of Child Health and Human Development
and the National Institute of Neurological Disorders and Stroke at the
National Institutes of Health.
NR 69
TC 8
Z9 8
U1 0
U2 11
PU W B SAUNDERS CO-ELSEVIER INC
PI PHILADELPHIA
PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA
SN 0001-2998
EI 1558-4623
J9 SEMIN NUCL MED
JI Semin. Nucl. Med.
PD NOV
PY 2013
VL 43
IS 6
BP 462
EP 473
DI 10.1053/j.semnuclmed.2013.06.005
PG 12
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 239WY
UT WOS:000326057900008
PM 24094713
ER
PT J
AU Coker-Appiah, DS
White, SF
Clanton, R
Yang, JJ
Martin, A
Blair, RJR
AF Coker-Appiah, Dionne S.
White, Stuart F.
Clanton, Roberta
Yang, Jiongjong
Martin, Alex
Blair, R. J. R.
TI Looming animate and inanimate threats: The response of the amygdala and
periaqueductal gray
SO SOCIAL NEUROSCIENCE
LA English
DT Article
DE Amygdala; Animacy; Threat; Looming; Periaqueductal gray
ID POSTTRAUMATIC-STRESS-DISORDER; FEAR; PREPAREDNESS; EXPRESSIONS;
AGGRESSION; BEHAVIOR; STIMULI; PHOBIAS; HUMANS
AB Looming stimuli are processed as threatening and activate basic neural defense systems. However, it is unclear how animacy information modulates this response. Participants (N=25) viewed threatening or neutral images that were either animate (animals) or inanimate (objects) and which either approached (loomed) or receded from the participant. The amygdala was responsive to emotional, animacy, and looming information (particularly to looming threats and looming animate stimuli). Periaqueductal gray was also sensitive to emotional information and particularly responsive to looming threats. The data are interpreted within category-specific models of the amygdala and temporal cortex.
C1 [Coker-Appiah, Dionne S.; White, Stuart F.; Clanton, Roberta; Blair, R. J. R.] NIMH, Sect Affect Cognit Neurosci, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
[Coker-Appiah, Dionne S.] Georgetown Univ, Dept Psychiat, Sch Med, Washington, DC 20007 USA.
[Yang, Jiongjong] Peking Univ, Dept Psychol, Beijing 100871, Peoples R China.
[Martin, Alex] NIMH, Lab Brain & Cognit, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
RP Coker-Appiah, DS (reprint author), Georgetown Univ, Dept Psychiat, Sch Med, 2115 Wisconsin Ave,NW,Suite 120, Washington, DC 20007 USA.
EM dms229@georgetown.edu
FU National Institute of Mental Health, National Institutes of Health
[1-ZIA-MH002860-08]; National Institutes of Health Combined Neuroscience
Review Board [93-M-0170]
FX This work was supported by the Intramural Research Program of the
National Institute of Mental Health, National Institutes of Health
[grant no. 1-ZIA-MH002860-08]. Ethical approval for this study was
granted by the National Institutes of Health Combined Neuroscience
Review Board under protocol 93-M-0170.
NR 32
TC 6
Z9 6
U1 1
U2 8
PU PSYCHOLOGY PRESS
PI HOVE
PA 27 CHURCH RD, HOVE BN3 2FA, EAST SUSSEX, ENGLAND
SN 1747-0919
EI 1747-0927
J9 SOC NEUROSCI-UK
JI Soc. Neurosci.
PD NOV 1
PY 2013
VL 8
IS 6
BP 621
EP 630
DI 10.1080/17470919.2013.839480
PG 10
WC Neurosciences; Psychology
SC Neurosciences & Neurology; Psychology
GA 243YE
UT WOS:000326353500008
PM 24066700
ER
PT J
AU Yan, YP
Shin, S
Jha, BS
Liu, QY
Sheng, JT
Li, FH
Zhan, M
Davis, J
Bharti, K
Zeng, XM
Rao, M
Malik, N
Vemuri, MC
AF Yan, Yiping
Shin, Soojung
Jha, Balendu Shekhar
Liu, Qiuyue
Sheng, Jianting
Li, Fuhai
Zhan, Ming
Davis, Janine
Bharti, Kapil
Zeng, Xianmin
Rao, Mahendra
Malik, Nasir
Vemuri, Mohan C.
TI Efficient and Rapid Derivation of Primitive Neural Stem Cells and
Generation of Brain Subtype Neurons From Human Pluripotent Stem Cells
SO STEM CELLS TRANSLATIONAL MEDICINE
LA English
DT Article
DE Astrocytes; Cell culture; Neural stem cell; Neural induction; Neural
differentiation; Oligodendrocytes; Neuron; Nestin
ID IN-VITRO; DIFFERENTIATION; PRECURSORS; IDENTITY
AB Human pluripotent stem cells (hPSCs), including human embryonic stem cells and human induced pluripotent stem cells, are unique cell sources for disease modeling, drug discovery screens, and cell therapy applications. The first step in producing neural lineages from hPSCs is the generation of neural stem cells (NSCs). Current methods of NSC derivation involve the time-consuming, labor-intensive steps of an embryoid body generation or coculture with stromal cell lines that result in low-efficiency derivation of NSCs. In this study, we report a highly efficient serum-free pluripotent stem cell neural induction medium that can induce hPSCs into primitive NSCs (pNSCs) in 7 days, obviating the need for time-consuming, laborious embryoid body generation or rosette picking. The pNSCs expressed the neural stem cell markers Pax6, Sox1, Sox2, and Nestin; were negative for Oct4; could be expanded for multiple passages; and could be differentiated into neurons, astrocytes, and oligodendrocytes, in addition to the brain region-specific neuronal subtypes GABAergic, dopaminergic, and motor neurons. Global gene expression of the transcripts of pNSCs was comparable to that of rosette-derived and human fetal-derived NSCs. This work demonstrates an efficient method to generate expandable pNSCs, which can be further differentiated into central nervous system neurons and glia with temporal, spatial, and positional cues of brain regional heterogeneity. This method of pNSC derivation sets the stage for the scalable production of clinically relevant neural cells for cell therapy applications in good manufacturing practice conditions.
C1 [Yan, Yiping; Shin, Soojung; Vemuri, Mohan C.] Life Technol, Primary & Stem Cell Culture Syst, Frederick, MD 21704 USA.
[Jha, Balendu Shekhar; Rao, Mahendra; Malik, Nasir] NIH, Natl Ctr Regenerat Med, Bethesda, MD 20892 USA.
[Liu, Qiuyue; Zeng, Xianmin] Buck Inst Age Res, Novato, CA USA.
[Sheng, Jianting; Li, Fuhai; Zhan, Ming] Methodist Hosp, Res Inst, Houston, TX 77030 USA.
[Davis, Janine; Bharti, Kapil] NEI, Unit Ocular & Stem Cell Translat Res, NIH, Bethesda, MD 20892 USA.
RP Vemuri, MC (reprint author), Life Technol, Primary & Stem Cell Syst, 7335 Execut Way, Frederick, MD 21704 USA.
EM mohan.vemuri@lifetech.com
OI Jha, Balendu Shekhar/0000-0002-6509-8171
NR 26
TC 22
Z9 22
U1 3
U2 16
PU ALPHAMED PRESS
PI DURHAM
PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA
SN 2157-6564
EI 2157-6580
J9 STEM CELL TRANSL MED
JI Stem Cells Transl. Med.
PD NOV
PY 2013
VL 2
IS 11
BP 862
EP 870
DI 10.5966/sctm.2013-0080
PG 9
WC Cell & Tissue Engineering
SC Cell Biology
GA 243JF
UT WOS:000326312000013
PM 24113065
ER
PT J
AU O'Neill, SC
Lipkus, IM
Sanderson, SC
Shepperd, J
Docherty, S
McBride, CM
AF O'Neill, Suzanne C.
Lipkus, Isaac M.
Sanderson, Saskia C.
Shepperd, James
Docherty, Sharron
McBride, Colleen M.
TI Motivations for genetic testing for lung cancer risk among young smokers
SO TOBACCO CONTROL
LA English
DT Article
DE Motivations; primary prevention; genetic testing; GSTM1; prevention;
cessation; addiction
ID SMOKING-BEHAVIOR; UNITED-STATES; UNREALISTIC OPTIMISM; HEALTH;
SUSCEPTIBILITY; PREVENTION
AB Objective To examine why young people might want to undergo genetic susceptibility testing for lung cancer despite knowing that tested gene variants are associated with small increases in disease risk.
Methods The authors used a mixed-method approach to evaluate motives for and against genetic testing and the association between these motivations and testing intentions in 128 college students who smoke.
Results Exploratory factor analysis yielded four reliable factors: Test Scepticism, Test Optimism, Knowledge Enhancement and Smoking Optimism. Test Optimism and Knowledge Enhancement correlated positively with intentions to test in bivariate and multivariate analyses (ps<0.001). Test Scepticism correlated negatively with testing intentions in multivariate analyses (p<0.05). Open-ended questions assessing testing motivations generally replicated themes of the quantitative survey.
Conclusion In addition to learning about health risks, young people may be motivated to seek genetic testing for reasons, such as gaining knowledge about new genetic technologies more broadly.
C1 [O'Neill, Suzanne C.] Georgetown Univ, Canc Control Program, Washington, DC 20007 USA.
[Lipkus, Isaac M.; Docherty, Sharron] Duke Univ, Sch Nursing, Durham, NC USA.
[Sanderson, Saskia C.] Mt Sinai Sch Med, New York, NY USA.
[Shepperd, James] Univ Florida, Dept Psychol, Gainesville, FL 32611 USA.
[McBride, Colleen M.] NHGRI, Social & Behav Res Branch, Bethesda, MD 20892 USA.
RP O'Neill, SC (reprint author), Georgetown Univ, Canc Control Program, 3300 Whitehaven St NW,Suite 4100, Washington, DC 20007 USA.
EM sco4@georgetown.edu
FU National Cancer Institute [RO1 CA01846]; American Cancer Society
[MRSG-10-110-01-CPPB]
FX Support for this work was provided by the National Cancer Institute
(Grant RO1 CA01846 to IML) and the American Cancer Society (Grant
MRSG-10-110-01-CPPB to SCO).
NR 35
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Z9 5
U1 0
U2 3
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 0964-4563
EI 1468-3318
J9 TOB CONTROL
JI Tob. Control
PD NOV
PY 2013
VL 22
IS 6
BP 406
EP 411
DI 10.1136/tobaccocontrol-2011-050306
PG 6
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 240OY
UT WOS:000326107800014
PM 22744911
ER
PT J
AU Koh, C
Turner, T
Zhao, XC
Minniti, CP
Feld, JJ
Simpson, J
Demino, M
Conrey, AK
Jackson, MJ
Seamon, C
Kleiner, DE
Kato, GJ
Heller, T
AF Koh, Christopher
Turner, Tiffany
Zhao, Xiongce
Minniti, Caterina P.
Feld, Jordan J.
Simpson, Jennifer
Demino, Mary
Conrey, Anna K.
Jackson, Mary J.
Seamon, Catherine
Kleiner, David E.
Kato, Gregory J.
Heller, Theo
TI Liver stiffness increases acutely during sickle cell vaso-occlusive
crisis
SO AMERICAN JOURNAL OF HEMATOLOGY
LA English
DT Article
ID CHRONIC HEPATITIS-C; TRANSIENT ELASTOGRAPHY; NONINVASIVE ASSESSMENT;
PORTAL-HYPERTENSION; DISEASE; FIBROSIS; ANEMIA; HEPATOPATHY;
HEMOCHROMATOSIS; CLASSIFICATION
AB Acute vaso-occlusive crisis (VOC) in sickle cell disease (SCD) is an important cause of end-organ damage. It is estimated that 10-39% of VOC occurs with hepatic involvement. Current assessments of hepatic involvement during VOC are unsatisfactory. We investigated transient elastography (TE) as a marker of hepatic involvement, its relationship with histology, and biochemical markers during VOC. SCD patients were evaluated with biochemical markers and TE at steady-state and during VOC. Change in TE and biochemical markers were correlated with length of hospital stay. When available, liver biopsy and tricuspid regurgitation velocity (TRV) at steady-state were correlated with TE. Twenty-three patients were evaluated (mean age=34.3 years, standard deviation=7.96). In 15 patients with liver biopsies, TE correlated with fibrosis (P=0.01) and TRV (P=0.0063), but not hepatic iron. Hemolysis biomarkers changed during VOC (P<0.022), but not alanine aminotransferase (ALT). Paired comparison of TE at steady-state and during VOC showed an increased from 6.2 to 12.3 kPa (P=0.0029). Increasing TE during VOC associated with increasing ALT and alkaline phosphatase (P=0.0088 and 0.0099, respectively). At steady-state, increasing inflammation on biopsy (P=0.0037) and TRV (P=0.0075) correlated with increasing TE during VOC. Increased hospital stay was associated with higher ALT (P=0.041), lower albumin (P=0.046), hemoglobin/hematocrit (P<0.0021) but not TE. TE may identify patients with hepatic involvement during VOC independent of biochemical measures. Increase in TE may reflect both hepatic passive congestion and hepatic involvement during VOC. TE may serve as a physiological biomarker for hepatic features of VOC. Am. J. Heamtol. 88:E250-E254, 2013. (c) 2013 Wiley Periodicals, Inc.
C1 [Koh, Christopher; Turner, Tiffany; Feld, Jordan J.; Simpson, Jennifer; Demino, Mary; Heller, Theo] NIDDK, Liver Dis Branch, NIH, Bethesda, MD 20892 USA.
[Zhao, Xiongce] NIDDK, Off Director, NIH, Bethesda, MD 20892 USA.
[Minniti, Caterina P.; Conrey, Anna K.; Jackson, Mary J.; Seamon, Catherine; Kato, Gregory J.] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA.
[Kleiner, David E.] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA.
RP Koh, C (reprint author), NIDDK, Liver Dis Branch, NIH, Bldg 10,Room 9B-16,10 Ctr Dr,MSC 1800, Bethesda, MD 20892 USA.
EM Christopher.Koh@nih.gov
RI Kato, Gregory/I-7615-2014;
OI Kato, Gregory/0000-0003-4465-3217; Kleiner, David/0000-0003-3442-4453
FU Intramural Research Programs of the National Institute of Diabetes and
Digestive and Kidney Diseases; National Heart, Lung, and Blood
Institute; National Cancer Institute
FX Contract grant sponsor: Intramural Research Programs of the National
Institute of Diabetes and Digestive and Kidney Diseases, the National
Heart, Lung, and Blood Institute and the National Cancer Institute.
NR 50
TC 2
Z9 2
U1 1
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0361-8609
EI 1096-8652
J9 AM J HEMATOL
JI Am. J. Hematol.
PD NOV
PY 2013
VL 88
IS 11
BP E250
EP E254
DI 10.1002/ajh.23532
PG 5
WC Hematology
SC Hematology
GA 239NX
UT WOS:000326033600002
PM 23828202
ER
PT J
AU Padalkar, MV
Spencer, RG
Pleshko, N
AF Padalkar, M. V.
Spencer, R. G.
Pleshko, N.
TI Near Infrared Spectroscopic Evaluation of Water in Hyaline Cartilage
SO ANNALS OF BIOMEDICAL ENGINEERING
LA English
DT Article
DE Water; Cartilage; Near infrared (NIR) spectroscopy; Partial least
squares (PLS) regression
ID HUMAN ARTICULAR-CARTILAGE; FIBER-OPTIC PROBE; NIR SPECTROSCOPY;
FISCHER,KARL TITRATION; DEGENERATIVE CARTILAGE; REFLECTANCE;
OSTEOARTHRITIS; SKIN; RELAXATION; DIFFUSION
AB In diseased conditions of cartilage such as osteoarthritis, there is typically an increase in water content from the average normal of 60-85% to greater than 90%. As cartilage has very little capability for self-repair, methods of early detection of degeneration are required, and assessment of water could prove to be a useful diagnostic method. Current assessment methods are either destructive, time consuming, or have limited sensitivity. Here, we investigated the hypotheses that non-destructive near infrared spectroscopy (NIRS) of articular cartilage can be used to differentiate between free and bound water, and to quantitatively assess water content. The absorbances centered at 5200 and 6890 cm(-1) were attributed to a combination of free and bound water, and to free water only, respectively. The integrated areas of both absorbance bands were found to correlate linearly with the absolute water content (R = 0.87 and 0.86) and with percent water content (R = 0.97 and 0.96) of the tissue. Partial least square models were also successfully developed and were used to predict water content, and percent free water. These data demonstrate that NIRS can be utilized to quantitatively determine water content in articular cartilage, and may aid in early detection of degenerative tissue changes in a laboratory setting, and with additional validations, possibly in a clinical setting.
C1 [Padalkar, M. V.; Pleshko, N.] Temple Univ, Dept Bioengn, Philadelphia, PA 19122 USA.
[Spencer, R. G.] NIA, NIH, Baltimore, MD 21224 USA.
RP Pleshko, N (reprint author), Temple Univ, Dept Bioengn, Philadelphia, PA 19122 USA.
EM npleshko@temple.edu
FU NIH [AR056145, EB000744]; Intramural Research Program at NIA
FX This study was supported by NIH AR056145 and EB000744 and the Intramural
Research Program at NIA.
NR 66
TC 16
Z9 16
U1 0
U2 12
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0090-6964
EI 1573-9686
J9 ANN BIOMED ENG
JI Ann. Biomed. Eng.
PD NOV
PY 2013
VL 41
IS 11
BP 2426
EP 2436
DI 10.1007/s10439-013-0844-0
PG 11
WC Engineering, Biomedical
SC Engineering
GA 236CZ
UT WOS:000325772900015
PM 23824216
ER
PT J
AU Williams, TH
Gumm, JM
Mendelson, TC
AF Williams, Tory H.
Gumm, Jennifer M.
Mendelson, Tamra C.
TI Sexual selection acting on a speciation trait in darters (Percidae:
Etheostoma)
SO BEHAVIORAL ECOLOGY
LA English
DT Article
DE association preference; behavioral isolation; female choice; male
nuptial color; model
ID MALE-MALE COMPETITION; FEMALE MATE CHOICE; LAKE VICTORIA CICHLIDS; WING
MELANIN PATTERN; MALE COLORATION; SPECIES RICHNESS; MATING PREFERENCES;
REPRODUCTIVE ISOLATION; BEHAVIORAL ISOLATION; PIERIS-OCCIDENTALIS
AB Despite theoretical support linking sexual selection for elaborate coloration and behavioral isolation, few empirical examples clearly demonstrate that the sexually dichromatic signals responsible for behavioral isolation between species are, or have been, subject to sexual selection within species. The present study investigates sexual selection on male nuptial coloration in Etheostoma barrenense, a darter species for which male color has been shown in a previous study to contribute to behavioral isolation from a sympatric congener. Through the use of motorized model fish, we demonstrate that female E. barrenense discriminate between the orange and red body hues of conspecific males and exhibit an association preference for orange over red models. Combined with the results from a previous study, these data provide evidence for a link between sexual selection and behavioral isolation and by extension for a role of sexual selection in speciation. A post hoc analysis of the colors modeled in darter visual space suggests that quantifying signal values as they are perceived, rather than expressed, provide a promising way of linking sexual selection and behavioral isolation.
C1 [Williams, Tory H.] NIAAA, Sect Model Synapt Syst, Lab Mol Physiol, NIH, Rockville, MD 20852 USA.
[Gumm, Jennifer M.] Stephen F Austin State Univ, Dept Biol, Nacogdoches, TX 75962 USA.
[Mendelson, Tamra C.] Univ Maryland Baltimore Cty, Dept Biol Sci, Baltimore, MD 21250 USA.
RP Williams, TH (reprint author), NIAAA, Sect Model Synapt Syst, Lab Mol Physiol, NIH, 5625 Fishers Lane, Rockville, MD 20852 USA.
EM tory.williams@nih.gov
FU National Science Foundation [DEB-0718987]
FX This research was partially funded by National Science Foundation grant
DEB-0718987 to T.C.M.
NR 82
TC 12
Z9 12
U1 3
U2 46
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1045-2249
EI 1465-7279
J9 BEHAV ECOL
JI Behav. Ecol.
PD NOV-DEC
PY 2013
VL 24
IS 6
BP 1407
EP 1414
DI 10.1093/beheco/art080
PG 8
WC Behavioral Sciences; Biology; Ecology; Zoology
SC Behavioral Sciences; Life Sciences & Biomedicine - Other Topics;
Environmental Sciences & Ecology; Zoology
GA 239BG
UT WOS:000325995900018
ER
PT J
AU Largent, E
Grady, C
Miller, FG
Wertheimer, A
AF Largent, Emily
Grady, Christine
Miller, Franklin G.
Wertheimer, Alan
TI MISCONCEPTIONS ABOUT COERCION AND UNDUE INFLUENCE: REFLECTIONS ON THE
VIEWS OF IRB MEMBERS
SO BIOETHICS
LA English
DT Article
DE coercion; undue influence; payment
ID CONSENT
AB Payment to recruit research subjects is a common practice but raises ethical concerns relating to the potential for coercion or undue influence. We conducted the first national study of IRB members and human subjects protection professionals to explore attitudes as to whether and why payment of research participants constitutes coercion or undue influence. Upon critical evaluation of the cogency of ethical concerns regarding payment, as reflected in our survey results, we found expansive or inconsistent views about coercion and undue influence that may interfere with valuable research. In particular, respondents appear to believe that coercion and undue influence lie on a continuum; by contrast, we argue that they are wholly distinct: whereas undue influence is a cognitive distortion relating to assessment of risks and benefits, coercion is a threat of harm. Because payment is an offer, rather than a threat, payment is never coercive.
C1 [Largent, Emily; Miller, Franklin G.; Wertheimer, Alan] NIH, Dept Bioeth, Bethesda, MD 20892 USA.
[Grady, Christine] NIH, Dept Bioeth, Ctr Clin, Bethesda, MD 20892 USA.
[Wertheimer, Alan] Univ Vermont, Burlington, VT 05405 USA.
RP Wertheimer, A (reprint author), NIH, 10 Ctr Dr,Bldg 10,Room 1C118, Bethesda, MD 20892 USA.
EM wertheimera@cc.nih.gov
NR 15
TC 12
Z9 12
U1 1
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0269-9702
EI 1467-8519
J9 BIOETHICS
JI Bioethics
PD NOV
PY 2013
VL 27
IS 9
BP 500
EP 507
DI 10.1111/j.1467-8519.2012.01972.x
PG 8
WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical
SC Social Sciences - Other Topics; Medical Ethics; Social Issues;
Biomedical Social Sciences
GA 237KD
UT WOS:000325867600005
PM 22493972
ER
PT J
AU Duan, Q
Liu, EY
Auer, PL
Zhang, GS
Lange, EM
Jun, G
Bizon, C
Jiao, S
Buyske, S
Franceschini, N
Carlson, CS
Hsu, L
Reiner, AP
Peters, U
Haessler, J
Curtis, K
Wassel, CL
Robinson, JG
Martin, LW
Haiman, CA
Le Marchand, L
Matise, TC
Hindorff, LA
Crawford, DC
Assimes, TL
Kang, HM
Heiss, G
Jackson, RD
Kooperberg, C
Wilson, JG
Abecasis, GR
North, KE
Nickerson, DA
Lange, LA
Li, Y
AF Duan, Qing
Liu, Eric Yi
Auer, Paul L.
Zhang, Guosheng
Lange, Ethan M.
Jun, Goo
Bizon, Chris
Jiao, Shuo
Buyske, Steven
Franceschini, Nora
Carlson, Chris S.
Hsu, Li
Reiner, Alex P.
Peters, Ulrike
Haessler, Jeffrey
Curtis, Keith
Wassel, Christina L.
Robinson, Jennifer G.
Martin, Lisa W.
Haiman, Christopher A.
Le Marchand, Loic
Matise, Tara C.
Hindorff, Lucia A.
Crawford, Dana C.
Assimes, Themistocles L.
Kang, Hyun Min
Heiss, Gerardo
Jackson, Rebecca D.
Kooperberg, Charles
Wilson, James G.
Abecasis, Goncalo R.
North, Kari E.
Nickerson, Deborah A.
Lange, Leslie A.
Li, Yun
TI Imputation of coding variants in African Americans: better performance
using data from the exome sequencing project
SO BIOINFORMATICS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; GENOTYPE IMPUTATION; RARE VARIANT; DESIGN;
ATHEROSCLEROSIS; HAPLOTYPES; DEEP; LOCI; TOOL; MAP
AB Although the 1000 Genomes haplotypes are the most commonly used reference panel for imputation, medical sequencing projects are generating large alternate sets of sequenced samples. Imputation in African Americans using 3384 haplotypes from the Exome Sequencing Project, compared with 2184 haplotypes from 1000 Genomes Project, increased effective sample size by 8.3-11.4% for coding variants with minor allele frequency 51%. No loss of imputation quality was observed using a panel built from phenotypic extremes. We recommend using haplotypes from Exome Sequencing Project alone or concatenation of the two panels over quality score-based post-imputation selection or IMPUTE2' s two-panel combination.
C1 [Duan, Qing; Zhang, Guosheng; Lange, Ethan M.; Lange, Leslie A.; Li, Yun] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA.
[Liu, Eric Yi; Li, Yun] Univ N Carolina, Dept Comp Sci, Chapel Hill, NC 27599 USA.
[Auer, Paul L.; Jiao, Shuo; Carlson, Chris S.; Hsu, Li; Reiner, Alex P.; Peters, Ulrike; Haessler, Jeffrey; Curtis, Keith; Kooperberg, Charles] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA.
[Lange, Ethan M.; Li, Yun] Univ N Carolina, Dept Biostat, Chapel Hill, NC 27599 USA.
[Jun, Goo; Kang, Hyun Min; Abecasis, Goncalo R.] Univ Michigan, Sch Publ Hlth, Dept Biostat, Ann Arbor, MI 48109 USA.
[Jun, Goo; Kang, Hyun Min; Abecasis, Goncalo R.] Univ Michigan, Sch Publ Hlth, Ctr Stat Genet, Ann Arbor, MI 48109 USA.
[Bizon, Chris] Univ N Carolina, Renaissance Comp Inst, Chapel Hill, NC 27599 USA.
[Buyske, Steven] Rutgers State Univ, Dept Stat, Piscataway, NJ 08854 USA.
[Buyske, Steven; Matise, Tara C.] Rutgers State Univ, Dept Genet, Piscataway, NJ 08854 USA.
[Franceschini, Nora; Heiss, Gerardo; North, Kari E.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27599 USA.
[Peters, Ulrike] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA.
[Wassel, Christina L.] Univ Pittsburgh, Grad Sch Publ Hlth, Div Epidemiol, Pittsburgh, PA 15261 USA.
[Robinson, Jennifer G.] Univ Iowa, Dept Epidemiol & Med, Iowa City, IA 52242 USA.
[Martin, Lisa W.] George Washington Univ, Sch Med & Hlth Sci, Div Cardiol, Washington, DC 20037 USA.
[Haiman, Christopher A.] Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA.
[Le Marchand, Loic] Univ Hawaii, Ctr Canc, Program Epidemiol, Honolulu, HI 96813 USA.
[Hindorff, Lucia A.] NHGRI, Div Genom Med, NIH, Bethesda, MD 20892 USA.
[Crawford, Dana C.] Vanderbilt Univ, Ctr Human Genet Res, Dept Mol Physiol & Biophys, Nashville, TN 37232 USA.
[Assimes, Themistocles L.] Stanford Univ, Sch Med, Dept Med, Stanford, CA 94305 USA.
[Jackson, Rebecca D.] Ohio State Univ, Div Endocrinol Diabet & Metab, Columbus, OH 43210 USA.
[Wilson, James G.] Univ Mississippi, Med Ctr, Dept Physiol & Biophys, Jackson, MS 39216 USA.
[Nickerson, Deborah A.] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA.
RP Li, Y (reprint author), Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA.
EM yunli@med.unc.edu
RI Liu, Eric Yi/B-6221-2016; Jun, Goo/M-5235-2016; Jun, Goo/F-1941-2017;
OI Jun, Goo/0000-0003-0891-0204; Jun, Goo/0000-0003-0891-0204; Martin, Lisa
Warsinger/0000-0003-4352-0914; Buyske, Steven/0000-0001-8539-5416
FU National Institutes of Health [R01HG006292, R01HG006703]
FX National Institutes of Health (R01HG006292 and R01HG006703 to Y.L.).
NR 40
TC 15
Z9 16
U1 0
U2 8
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 2013
VL 29
IS 21
BP 2744
EP 2749
DI 10.1093/bioinformatics/btt477
PG 6
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 239BW
UT WOS:000325997500011
PM 23956302
ER
PT J
AU Keyak, JH
Sigurdsson, S
Karlsdottir, GS
Oskarsdottir, D
Sigmarsdottir, A
Kornak, J
Harris, TB
Sigurdsson, G
Jonsson, BY
Siggeirsdottir, K
Eiriksdottir, G
Gudnason, V
Lang, TF
AF Keyak, J. H.
Sigurdsson, S.
Karlsdottir, G. S.
Oskarsdottir, D.
Sigmarsdottir, A.
Kornak, J.
Harris, T. B.
Sigurdsson, G.
Jonsson, B. Y.
Siggeirsdottir, K.
Eiriksdottir, G.
Gudnason, V.
Lang, T. F.
TI Effect of finite element model loading condition on fracture risk
assessment in men and women: The AGES-Reykjavik study
SO BONE
LA English
DT Article
DE Hip fracture; Femur; Bone strength; Finite element analysis;
Osteoporosis; Quantitative computed tomography
ID PROXIMAL FEMORAL STRENGTH; GENE/ENVIRONMENT SUSCEPTIBILITY-REYKJAVIK;
CT-SCAN DATA; HIP FRACTURE; IMPACT DIRECTION; TRABECULAR BONE; FEMUR;
PREDICTION; ASSOCIATION; DXA
AB Proximal femoral (hip) strength computed by subject-specific CT scan-based finite element (FE) models has been explored as an improved measure for identifying subjects at risk of hip fracture. However, to our knowledge, no published study has reported the effect of loading condition on the association between incident hip fracture and hip strength. In the present study, we performed a nested age- and sex-matched case-control study in the Age Gene/Environment Susceptibility (AGES) Reykjavik cohort Baseline (pre-fracture) quantitative CT (QCT) scans of 5500 older male and female subjects were obtained. During 4-7 years follow-up, 51 men and 77 women sustained hip fractures. Ninety-seven men and 152 women were randomly selected as controls from a pool of age- and sex-matched subjects. From the QCT data, FE models employing nonlinear material properties computed FE-strength of the left hip of each subject in loading from a fall onto the posterolateral (F-PL), posterior (F-P) and lateral (F-L) aspects of the greater trochanter (patent pending). For comparison, FE strength in stance loading (F-Stance) and total femur areal bone mineral density (aBMD) were also computed. For all loading conditions, the reductions in strength associated with fracture in men were more than twice those in women (p <= 0.01). For fall loading specifically, posterolateral loading in men and posterior loading in women were most strongly associated with incident hip fracture. After adjusting for aBMD, the association between F-P and fracture in women fell short of statistical significance (p = 0.08), indicating that FE strength provides little advantage over aBMD for identifying female hip fracture subjects. However, in men, after controlling for aBMD, F-PL was 424 N (11%) less in subjects with fractures than in controls (p = 0.003). Thus, in men, FE models of posterolateral loading include information about incident hip fracture beyond that in aBMD. (c) 2013 Elsevier Inc. All rights reserved.
C1 [Keyak, J. H.] Univ Calif Irvine, Dept Radiol Sci, Irvine, CA 92697 USA.
[Keyak, J. H.] Univ Calif Irvine, Dept Biomed Engn, Irvine, CA 92697 USA.
[Keyak, J. H.] Univ Calif Irvine, Dept Mech & Aerosp Engn, Irvine, CA 92717 USA.
[Sigurdsson, S.; Karlsdottir, G. S.; Oskarsdottir, D.; Sigmarsdottir, A.; Sigurdsson, G.; Siggeirsdottir, K.; Eiriksdottir, G.; Gudnason, V.] Iceland Heart Assoc Res Inst, Kopavogur, Iceland.
[Oskarsdottir, D.; Sigurdsson, G.; Gudnason, V.] Univ Iceland, Reykjavik, Iceland.
[Kornak, J.; Lang, T. F.] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94143 USA.
[Kornak, J.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA.
[Harris, T. B.] NIA, Lab Epidemiol Demog & Biometry, Intramural Res Program, Bethesda, MD 20892 USA.
[Sigurdsson, G.] Landspitalinn Univ Hosp, Reykjavik, Iceland.
[Jonsson, B. Y.] Skane Univ Hosp, Dept Orthoped, Malmo, Sweden.
RP Keyak, JH (reprint author), Univ Calif Irvine, Dept Radiol Sci, Irvine, CA 92697 USA.
EM jhkeyak@uci.edu
RI Gudnason, Vilmundur/K-6885-2015
OI Gudnason, Vilmundur/0000-0001-5696-0084
FU NIH/NIA [R01AG028832]; NIH/NIAMS [R01AR46197]; NIH [N01-AG-12100]; NIA
Intramural Research Program; Hjartavernd (the Icelandic Heart
Association); Althingi (the Icelandic Parliament)
FX This study was supported by NIH/NIA R01AG028832 and NIH/NIAMS
R01AR46197. The Age, Gene/Environment Susceptibility Reykjavik Study is
funded by NIH contract N01-AG-12100, the NIA Intramural Research
Program, Hjartavernd (the Icelandic Heart Association), and the Althingi
(the Icelandic Parliament). The study was approved by the Icelandic
National Bioethics Committee, (VSN: 00-063) and the Data Protection
Authority. The researchers are indebted to the participants for their
willingness to participate in the study.
NR 26
TC 17
Z9 19
U1 0
U2 8
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 8756-3282
EI 1873-2763
J9 BONE
JI Bone
PD NOV
PY 2013
VL 57
IS 1
BP 18
EP 29
DI 10.1016/j.bone.2013.07.028
PG 12
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 235TC
UT WOS:000325742600003
PM 23907032
ER
PT J
AU Carballido-Gamio, J
Harnish, R
Saeed, I
Streeper, T
Sigurdsson, S
Amin, S
Atkinson, EJ
Therneau, TM
Siggeirsdottir, K
Cheng, XG
Melton, LJ
Keyak, JH
Gudnason, V
Khosla, S
Harris, TB
Lang, TF
AF Carballido-Gamio, Julio
Harnish, Roy
Saeed, Isra
Streeper, Timothy
Sigurdsson, Sigurdur
Amin, Shreyasee
Atkinson, Elizabeth J.
Therneau, Terry M.
Siggeirsdottir, Kristin
Cheng, Xiaoguang
Melton, L. Joseph, III
Keyak, Joyce H.
Gudnason, Vilmundur
Khosla, Sundeep
Harris, Tamara B.
Lang, Thomas F.
TI Structural patterns of the proximal femur in relation to age and hip
fracture risk in women
SO BONE
LA English
DT Article
DE Osteoporosis; Proximal femur; Statistical parametric mapping;
Tensor-based morphometry (TBM); Age; Fracture
ID TENSOR-BASED MORPHOMETRY; VOXEL-BASED MORPHOMETRY; GENE/ENVIRONMENT
SUSCEPTIBILITY-REYKJAVIK; FEMORAL-NECK; COMPUTED-TOMOGRAPHY;
GROWTH-PATTERNS; HUMAN BRAIN; BONE; STRENGTH; GEOMETRY
AB Fractures of the proximal femur are the most devastating outcome of osteoporosis. It is generally understood that age-related changes in hip structure confer increased risk, but there have been few explicit comparisons of such changes in healthy subjects to those with hip fracture. In this study, we used quantitative computed tomography and tensor-based morphometry (TBM) to identify three-dimensional internal structural patterns of the proximal femur associated with age and with incident hip fracture. A population-based cohort of 349 women representing a broad age range (21-97 years) was included in this study, along with a cohort of 222 older women (mean age 79 7 years) with (n = 74) and without (n = 148) incident hip fracture. Images were spatially normalized to a standardized space, and age- and fracture-specific morphometric features were identified based on statistical maps of shape features described as local changes of bone volume. Morphometric features were visualized as maps of local contractions and expansions, and significance was displayed as Student's t-test statistical maps. Significant age-related changes included local expansions of regions low in volumetric bone mineral density (vBMD) and local contractions of regions high in vBMD. Some significant fracture-related features resembled an accentuated aging process, including local expansion of the superior aspect of the trabecular bone compartment in the femoral neck, with contraction of the adjoining cortical bone. However, other features were observed only in the comparison of hip fracture subjects with age-matched controls including focal contractions of the cortical bone at the superior aspect of the femoral neck, the lateral cortical bone just inferior to the greater trochanter, and the anterior intertrochanteric region. Results of this study support the idea that the spatial distribution of morphometric features is relevant to age-related changes in bone and independent to fracture risk. In women, the identification by TBM of fracture-specific morphometric alterations of the proximal femur, in conjunction with vBMD and clinical risk factors, may improve hip fracture prediction. (C) 2013 Elsevier Inc. All rights reserved.
C1 [Carballido-Gamio, Julio; Harnish, Roy; Saeed, Isra; Streeper, Timothy; Lang, Thomas F.] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94143 USA.
[Sigurdsson, Sigurdur; Siggeirsdottir, Kristin; Gudnason, Vilmundur] Iceland Heart Assoc, Kopavogur, Iceland.
[Amin, Shreyasee; Melton, L. Joseph, III] Mayo Clin, Coll Med, Dept Hlth Sci Res, Div Epidemiol, Rochester, MN USA.
[Amin, Shreyasee] Mayo Clin, Coll Med, Dept Internal Med, Div Rheumatol, Rochester, MN USA.
[Atkinson, Elizabeth J.; Therneau, Terry M.] Mayo Clin, Coll Med, Dept Hlth Sci Res, Div Biomed Stat & Informat, Rochester, MN USA.
[Cheng, Xiaoguang] Beijing Ji Shui Tan Hosp, Dept Radiol, Beijing, Peoples R China.
[Melton, L. Joseph, III; Khosla, Sundeep] Mayo Clin, Coll Med, Dept Internal Med, Div Endocrinol Diabet Metab & Nutr, Rochester, MN USA.
[Keyak, Joyce H.] Univ Calif Irvine, Dept Radiol Sci, Irvine, CA 92717 USA.
[Gudnason, Vilmundur] Univ Iceland, Reykjavik, Iceland.
[Harris, Tamara B.] NIA, Intramural Res Program, Bethesda, MD 20892 USA.
RP Lang, TF (reprint author), 185 Berry St,Suite 350, San Francisco, CA 94143 USA.
EM Thomas.Lang@ucsf.edu
RI Gudnason, Vilmundur/K-6885-2015;
OI Gudnason, Vilmundur/0000-0001-5696-0084; Khosla,
Sundeep/0000-0002-2936-4372; Lang, Thomas/0000-0002-3720-8038
FU NIH/NIA [R01AG028832, R01AG034676, UL1 TR000135]; NIH/NIAMS [R01AR46197,
R01AR027065]; NIH/NIA Professional Services Contract
[HHSN311200900345P]; NIH [N01-AG-12100]; NIA Intramural Research
Program; Hjartavernd (the Icelandic Heart Association); Althingi (the
Icelandic Parliament)
FX This study was supported by NIH/NIA R01AG028832, NIH/NIAMS R01AR46197,
NIH/NIA Professional Services Contract HHSN311200900345P, NIH/NIAMS
R01AR027065, and NIH/NIA R01AG034676 and UL1 TR000135 (Center for
Translational Science Activities). The Age, Gene/Environment
Susceptibility Reykjavik study is funded by NIH contract N01-AG-12100,
the NIA Intramural Research Program, Hjartavernd (the Icelandic Heart
Association), and the Althingi (the Icelandic Parliament).
NR 43
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U1 0
U2 17
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 8756-3282
EI 1873-2763
J9 BONE
JI Bone
PD NOV
PY 2013
VL 57
IS 1
BP 290
EP 299
DI 10.1016/j.bone.2013.08.017
PG 10
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 235TC
UT WOS:000325742600039
PM 23981658
ER
PT J
AU Kenworthy, L
Wallace, GL
Birn, R
Milleville, SC
Case, LK
Bandettini, PA
Martin, A
AF Kenworthy, Lauren
Wallace, Gregory L.
Birn, Rasmus
Milleville, Shawn C.
Case, Laura K.
Bandettini, Peter A.
Martin, Alex
TI Aberrant neural mediation of verbal fluency in autism spectrum disorders
SO BRAIN AND COGNITION
LA English
DT Article
DE Autism; Verbal fluency; fMRI; Executive function; Left inferior frontal
gyrus
ID HIGH-FUNCTIONING AUTISM; VENTROLATERAL PREFRONTAL CORTEX; FRONTAL-LOBE
LESIONS; WORKING-MEMORY TASK; EXECUTIVE FUNCTIONS; REPETITIVE BEHAVIOR;
BRAIN ACTIVATION; SENTENCE COMPREHENSION; ASPERGERS-DISORDER; COGNITIVE
CONTROL
AB Objective: Contrasts of verbal fluency and automatic speech provide an opportunity to evaluate the neural underpinnings of generativity and flexibility in autism spectrum disorders (ASD).
Method: We used functional magnetic resonance imaging (fMRI) to contrast brain activity in high functioning ASD (n = 17, mean verbal IQ = 117) and neurotypical (NT; n = 20, mean verbal IQ = 112) adolescent and young adult males (12-23 years). Participants responded to three word generation conditions: automatic speech (reciting months), category fluency, and letter fluency.
Results: Our paradigm closely mirrored behavioral fluency tasks by requiring overt, free recall word generation while controlling for differences in verbal output between the groups and systematically increasing the task demand. The ASD group showed reduced neural response compared to the NT participants during fluency tasks in multiple regions of left anterior and posterior cortices, and sub-cortical structures. Six of these regions fell in cortico-striatal circuits previously linked to repetitive behaviors (Langen, Durston, Kas, van Engeland, & Staal, 2011), and activity in two of them (putamen and thalamus) was negatively correlated with autism repetitive behavior symptoms in the ASD group. In addition, response in left inferior frontal gyrus was differentially modulated in the ASD, relative to the NT, group as a function of task demand.
Conclusions: These data indicate a specific, atypical brain response in ASD to demanding generativity tasks that may have relevance to repetitive behavior symptoms in ASD as well as to difficulties generating original verbal responses. Published by Elsevier Inc.
C1 [Kenworthy, Lauren; Wallace, Gregory L.; Birn, Rasmus; Milleville, Shawn C.; Case, Laura K.; Bandettini, Peter A.; Martin, Alex] NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA.
[Kenworthy, Lauren] Childrens Natl Med Ctr, Ctr Autism Spectrum Disorders, Rockville, MD 20850 USA.
RP Kenworthy, L (reprint author), NIMH, Lab Brain & Cognit, 10 Ctr Dr,Room 4C104,MSC 1366, Bethesda, MD 20892 USA.
EM lkenwort@cnmc.org; gregwallace@mail.nih.-gov; rbirn@wisc.edu;
millevis@mail.nih.gov; lkcase@gmail.com; bandettp@mail.nih.gov;
alexmar-tin@mail.nih.gov
OI Case, Laura/0000-0003-3730-2451; Wallace, Gregory/0000-0003-0329-5054
FU National Institute of Mental Health, National Institutes of Health,
Division of Intramural Research under National Institutes of Health
[10-M-0027]; Guldelsky Family Foundation
FX This study was supported by the National Institute of Mental Health,
National Institutes of Health, Division of Intramural Research, and it
was conducted under National Institutes of Health Clinical Study
Protocol 10-M-0027 (ClinicalTrials.gov ID NCT01031407). In addition,
Lauren Kenworthy received support from the Guldelsky Family Foundation.
The authors thank the children and their families who participated in
the investigation, Ben Yerys for valuable feedback regarding the
manuscript, and Eunice Dixon for editorial assistance.
NR 82
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U1 2
U2 22
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0278-2626
EI 1090-2147
J9 BRAIN COGNITION
JI Brain Cogn.
PD NOV
PY 2013
VL 83
IS 2
BP 218
EP 226
DI 10.1016/j.bandc.2013.08.003
PG 9
WC Neurosciences; Psychology, Experimental
SC Neurosciences & Neurology; Psychology
GA 235SI
UT WOS:000325740600007
PM 24056237
ER
PT J
AU Lamm, C
Pine, DS
Fox, NA
AF Lamm, C.
Pine, D. S.
Fox, N. A.
TI Impact of negative affectively charged stimuli and response style on
cognitive-control-related neural activation: An ERP study
SO BRAIN AND COGNITION
LA English
DT Article
DE Emotion; AX-CPT; Reactive control; Proactive control; N2; LORETA;
Prefrontal neural activation
ID EMOTION REGULATION; WORKING-MEMORY; MECHANISMS; CHILDREN; INTERFERENCE;
PERFORMANCE
AB The canonical AX-CPT task measures two forms of cognitive control: sustained goal-oriented control ("proactive" control) and transient changes in cognitive control following unexpected events ("reactive" control). We modified this task by adding negative and neutral International Affective Picture System (IAPS) pictures to assess the effects of negative emotion on these two forms of cognitive control. Proactive and reactive control styles were assessed based on measures of behavior and electrophysiology, including the N2 event-related potential component and source space activation (Low Resolution Tomography [LORETA]). We found slower reaction-times and greater DLPFC activation for negative relative to neutral stimuli. Additionally, we found that a proactive style of responding was related to less prefrontal activation (interpreted to reflect increased efficiency of processing) during actively maintained previously cued information and that a reactive style of responding was related to less prefrontal activation (interpreted to reflect increased efficiency of processing) during just-in-time environmentally triggered information. This pattern of results was evident in relatively neutral contexts, but in the face of negative emotion, these associations were not found, suggesting potential response style-by-emotion interaction effects on prefrontal neural activation. (C) 2013 Elsevier Inc. All rights reserved.
C1 [Lamm, C.] Univ New Orleans, Dept Psychol, New Orleans, LA 70148 USA.
[Pine, D. S.] NIMH, Intramural Res Program, Sect Dev & Affect Neurosci, Bethesda, MD 20892 USA.
[Fox, N. A.] Univ Maryland, Dept Human Dev & Quantitat Methodol, Child Dev Lab, Catonsville, MD 21228 USA.
RP Lamm, C (reprint author), Univ New Orleans, Dept Psychol, New Orleans, LA 70148 USA.
EM clamm@uno.edu
FU National Institute of Mental Health [P50MH078105]
FX The project described was supported by Grant Number P50MH078105 to Megan
R. Gunnar from the National Institute of Mental Health. The content is
solely the responsibility of the authors and does not necessarily
represent the official views of the National Institute of Mental Health
or the National Institutes of Health. The authors also thank Anna Kresse
for her dedication in collecting this data in a timely manner.
NR 22
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U1 3
U2 28
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0278-2626
EI 1090-2147
J9 BRAIN COGNITION
JI Brain Cogn.
PD NOV
PY 2013
VL 83
IS 2
BP 234
EP 243
DI 10.1016/j.bandc.2013.07.012
PG 10
WC Neurosciences; Psychology, Experimental
SC Neurosciences & Neurology; Psychology
GA 235SI
UT WOS:000325740600009
PM 24021156
ER
PT J
AU Loga, F
Domes, K
Freichel, M
Flockerzi, V
Dietrich, A
Birnbaumer, L
Hofmann, F
Wegener, JW
AF Loga, Florian
Domes, Katrin
Freichel, Marc
Flockerzi, Veit
Dietrich, Alexander
Birnbaumer, Lutz
Hofmann, Franz
Wegener, Joeg W.
TI The role of cGMP/cGKI signalling and Trpc channels in regulation of
vascular tone
SO CARDIOVASCULAR RESEARCH
LA English
DT Article
DE Phenylephrine; Smooth muscle; Relaxation; Nitric oxide; Endothelium
ID RECEPTOR POTENTIAL CHANNELS; ARTERIAL SMOOTH-MUSCLE; NITRIC-OXIDE
SYNTHASE; PROTEIN-KINASE-G; ENDOTHELIAL-CELLS; MICE; VASORELAXATION;
INHIBITION; ACTIVATION; EXPRESSION
AB Signalling via cGMP-dependent protein kinase I (cGKI) is the major pathway in vascular smooth muscle (SM), by which endothelial NO regulates vascular tone. Recent evidence suggests that canonical transient receptor potential (Trpc) channels are targets of cGKI in SM and mediate the relaxant effects of cGMP signalling. We tested this concept by investigating the role of cGMP/cGKI signalling on vascular tone and peripheral resistance using Trpc6(/), Trpc3(/), Trpc3(/)/6(/), Trpc1(/)/3(/)/6(/), and SM-specific cGKI(/) (sm-cGKI(/)) mice.
-Adrenergic stimulation induced similar contractions in L-NG-nitroarginine methyl ester (l-NAME)-treated aorta and comparably increased peripheral pressure in hind limbs from all mouse lines investigated. After -adrenergic stimulation, 8-Br-cGMP diminished similarly aortic tone and peripheral pressure in control, Trpc6(/), Trpc3(/), Trpc3(/)/6(/), and Trpc1(/)/3(/)/6(/) mice but not in sm-cGKI(/) mice. In untreated aorta, -adrenergic stimulation induced similar contractions in the aorta from control and Trpc3(/) mice but larger contractions in sm-cGKI(/), Trpc6(/), Trpc3(/)/6(/), and Trpc1(/)/3(/)/6(/) mice, indicating a functional link between cGKI and Trpc6 channels. Trpc3 channels were detected by immunocytochemistry in both isolated aortic smooth muscle cells (SMCs) and aortic endothelial cells (ECs), whereas Trpc6 channels were detected only in ECs. Phenylephrine-stimulated Ca-2 levels were similar in SMCs from control (Ctr) and Trpc6(/) mice. Carbachol-stimulated Ca-2 levels were reduced in ECs from Trpc6(/) mice. Stimulated Ca-2 levels were lowered by 8-Br-cGMP in Ctr but not in Trpc6(/) ECs.
The results suggest that cGKI and Trpc1,3,6 channels are not functionally coupled in vascular SM. Deletion of Trpc6 channels impaired endothelial cGKI signalling and vasodilator tone in the aorta.
C1 [Loga, Florian; Domes, Katrin; Hofmann, Franz; Wegener, Joeg W.] Tech Univ Munich, FOR923, Inst Pharmakol & Toxikol, D-80802 Munich, Germany.
[Freichel, Marc] Heidelberg Univ, Pharmakol Inst, D-69120 Heidelberg, Germany.
[Freichel, Marc; Flockerzi, Veit] Univ Saarland, Med Fak, D-66421 Homburg, Germany.
[Dietrich, Alexander] Univ Munich, Walther Straub Inst Pharmakol & Toxikol, D-80539 Munich, Germany.
[Birnbaumer, Lutz] NIEHS, Dept Hlth & Human Serv, NIH, Res Triangle Pk, NC 27709 USA.
RP Wegener, JW (reprint author), Tech Univ Munich, FOR923, Inst Pharmakol & Toxikol, Biedersteiner Str 29, D-80802 Munich, Germany.
EM joerg.wegener@mytum.de
OI Dietrich, Alexander/0000-0002-1168-8707
FU Deutsche Forschungsgemeinschaft; Fond der Chemischen Industrie;
Intramural Research Program of the NIH [Z01-ES-101684]
FX The work was funded by grants from Deutsche Forschungsgemeinschaft, Fond
der Chemischen Industrie, and by the Intramural Research Program of the
NIH (Project Z01-ES-101684 to L.B.).
NR 36
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Z9 9
U1 0
U2 10
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0008-6363
EI 1755-3245
J9 CARDIOVASC RES
JI Cardiovasc. Res.
PD NOV 1
PY 2013
VL 100
IS 2
BP 280
EP 287
DI 10.1093/cvr/cvt176
PG 8
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 239IG
UT WOS:000326015200014
PM 23832809
ER
PT J
AU Berger, VW
Gudehithlu, SK
AF Berger, Vance W.
Gudehithlu, Sheila K.
TI Re: Compalati E, Canonica GW. Efficacy and safety of rupatadine for
allergic rhino-conjunctivitis: a systematic review of randomized,
double-blind, placebo-controlled studies with meta-analysis. Curr Med
Res Opin 2013 Jul 5. DOI: 10.1185/03007995.2013.837386.
SO CURRENT MEDICAL RESEARCH AND OPINION
LA English
DT Letter
ID 10 MG; RHINITIS
C1 [Berger, Vance W.] NCI, Rockville, MD 20850 USA.
[Berger, Vance W.; Gudehithlu, Sheila K.] Univ Maryland Baltimore Cty, Biometry Res Grp, Natl Canc Inst, Rockville, MD 20850 USA.
[Gudehithlu, Sheila K.] Univ Illinois, Natl Canc Inst, Rockville, MD 20850 USA.
RP Berger, VW (reprint author), NCI, 9609 Med Ctr Dr, Rockville, MD 20850 USA.
EM vb78c@nih.gov
NR 7
TC 2
Z9 2
U1 0
U2 2
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 0300-7995
EI 1473-4877
J9 CURR MED RES OPIN
JI Curr. Med. Res. Opin.
PD NOV
PY 2013
VL 29
IS 11
BP 1553
EP 1554
DI 10.1185/03007995.2013.837386
PG 2
WC Medicine, General & Internal; Medicine, Research & Experimental
SC General & Internal Medicine; Research & Experimental Medicine
GA 237FD
UT WOS:000325853100018
PM 23971648
ER
PT J
AU Grice, BA
Mason, CC
Weil, EJ
Knowler, WC
Pomeroy, J
AF Grice, Brian A.
Mason, Clinton C.
Weil, E. Jennifer
Knowler, William C.
Pomeroy, Jeremy
TI The relationship between insulin sensitivity and maximal oxygen uptake
is confounded by method of adjustment for body composition
SO DIABETES & VASCULAR DISEASE RESEARCH
LA English
DT Article
DE VO(2)max; insulin sensitivity; ratio adjustment; maximal oxygen uptake;
per-weight standard
ID CARDIORESPIRATORY FITNESS; STATISTICAL CONSIDERATIONS; ASSOCIATION;
OVERWEIGHT; GLUCOSE; FATNESS; ADULTS; WOMEN; MEN
AB Background: The use of ratios for analyzing physiologic variables often creates spurious associations.
Methods: Results of a euglycaemic clamp, a graded exercise test to measure maximal oxygen uptake (VO(2)max) and underwater weighing in 358 nondiabetic adults (166 women and 192 men) were used to compare the effects of weight standardization by division or by partial Spearman correlations on the association between VO(2)max and insulin sensitivity.
Results: VO(2)max and insulin sensitivity were negatively correlated when VO(2)max was divided by weight. When partial Spearman correlations were used to adjust VO(2)max for body composition, the correlation between VO(2)max and insulin sensitivity was greatly diminished.
Conclusions: Division of VO(2)max by weight does not adjust for weight, but it creates spurious associations between VO(2)max and insulin sensitivity.
C1 [Grice, Brian A.; Weil, E. Jennifer; Knowler, William C.; Pomeroy, Jeremy] NIDDK, Phoenix, AZ 85014 USA.
[Mason, Clinton C.] Huntsman Canc Inst, Salt Lake City, UT USA.
RP Pomeroy, J (reprint author), NIDDK, 1550 E Indian Sch Rd, Phoenix, AZ 85014 USA.
EM Jeremy.pomeroy@nih.gov
FU NIDDK Intramural Research Program
FX This research was supported by the NIDDK Intramural Research Program.
NR 17
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Z9 0
U1 0
U2 1
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 1479-1641
EI 1752-8984
J9 DIABETES VASC DIS RE
JI Diabetes Vasc. Dis. Res.
PD NOV
PY 2013
VL 10
IS 6
BP 530
EP 535
DI 10.1177/1479164113501529
PG 6
WC Endocrinology & Metabolism; Peripheral Vascular Disease
SC Endocrinology & Metabolism; Cardiovascular System & Cardiology
GA 236NH
UT WOS:000325803800008
PM 24062163
ER
PT J
AU Young, WS
AF Young, W. Scott
TI Shedding Heat on Oxytocin
SO ENDOCRINOLOGY
LA English
DT Editorial Material
ID RECEPTOR-DEFICIENT MICE; SOCIAL RECOGNITION; AUTISM LOCI; GENOME-WIDE;
PARTURITION; MOUSE; BEHAVIOR; IMPAIRS; SEARCH; GENES
C1 NIMH, NIH, Dept Hlth & Human Serv, Sect Neural Gene Express, Bethesda, MD 20892 USA.
RP Young, WS (reprint author), NIMH, NIH, Dept Hlth & Human Serv, Sect Neural Gene Express, Bethesda, MD 20892 USA.
EM wsy@mail.nih.gov
RI Young, W Scott/A-9333-2009
OI Young, W Scott/0000-0001-6614-5112
FU NIMH NIH HHS [Z01 MH002498, Z01-MH-002498-24]
NR 32
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U1 0
U2 12
PU ENDOCRINE SOC
PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0013-7227
EI 1945-7170
J9 ENDOCRINOLOGY
JI Endocrinology
PD NOV
PY 2013
VL 154
IS 11
BP 3961
EP 3962
DI 10.1210/en.2013-1885
PG 2
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 238HI
UT WOS:000325935200004
PM 24141993
ER
PT J
AU Pedram, A
Razandi, M
Korach, KS
Narayanan, R
Dalton, JT
Levin, ER
AF Pedram, Ali
Razandi, Mahnaz
Korach, Kenneth S.
Narayanan, Ramesh
Dalton, James T.
Levin, Ellis R.
TI ER beta Selective Agonist Inhibits Angiotensin-Induced Cardiovascular
Pathology in Female Mice
SO ENDOCRINOLOGY
LA English
DT Article
ID ESTROGEN-RECEPTOR-BETA; LEFT-VENTRICULAR HYPERTROPHY; HORMONE
REPLACEMENT THERAPY; HYPERTENSIVE HEART-DISEASE; CARDIAC-HYPERTROPHY;
POSTMENOPAUSAL WOMEN; IN-VIVO; MYOCARDIAL-INFARCTION; TARGETED
DISRUPTION; NATRIURETIC-PEPTIDE
AB Cardiac hypertrophy in humans can progress to cardiac failure if the underlying impetus is poorly controlled. An important direct stimulator of hypertrophy and its progression is the angiotensin II (AngII) peptide. AngII also causes hypertension that indirectly contributes to cardiac hypertrophy. Others and we have shown that estrogens acting through the estrogen receptor (ER)-beta can inhibit AngII-induced or other forms of cardiac hypertrophy in mice. However, the proliferative effects of estrogen in breast and uterus that promote the development of malignancy preclude using the steroid to prevent cardiac disease progression. We therefore tested whether an ER beta selective agonist, beta-LGND2, can prevent hypertension and cardiac pathology in female mice. AngII infusion over 3 weeks significantly stimulated systolic and diastolic hypertension, cardiac hypertrophy, and cardiac fibrosis, all significantly prevented by beta-LGND2 in wild-type but not in ER beta genetically deleted mice. AngII stimulated the Akt kinase to phosphorylate and inhibit the glycogen synthase kinase-3 beta kinase, leading to GATA4 transcription factor activation and hypertrophic mRNA expression. As a novel mechanism, all these actions were opposed by estradiol and beta-LGND2. Our findings provide additional understanding of the antihypertrophic effects of ER beta and serve as an impetus to test specific receptor agonists in humans to prevent the worsening of cardiovascular disease.
C1 [Razandi, Mahnaz; Levin, Ellis R.] Dept Vet Affairs Med Ctr, Div Endocrinol, Long Beach, CA 90822 USA.
[Pedram, Ali; Levin, Ellis R.] Univ Calif Irvine, Dept Med, Irvine, CA 92717 USA.
[Levin, Ellis R.] Univ Calif Irvine, Dept Biochem, Irvine, CA 92717 USA.
[Korach, Kenneth S.] NIEHS, Res Triangle Pk, NC 27709 USA.
[Dalton, James T.] GTx Inc, Memphis, TN 38163 USA.
RP Levin, ER (reprint author), Long Beach Vet Affairs Med Ctr, Med Serv I 111, 5901 East 7th St, Long Beach, CA 90822 USA.
EM ellis.levin@va.gov
OI dalton, James T/0000-0002-3915-7326; Korach, Kenneth/0000-0002-7765-418X
FU Research Service of the Department of Veterans Affairs; National
Institutes of Health [CA-10036]
FX This work was supported by grants from the Research Service of the
Department of Veterans Affairs and National Institutes of Health Grant
CA-10036 (to E.R.L.).
NR 53
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U1 0
U2 1
PU ENDOCRINE SOC
PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0013-7227
EI 1945-7170
J9 ENDOCRINOLOGY
JI Endocrinology
PD NOV
PY 2013
VL 154
IS 11
BP 4352
EP 4364
DI 10.1210/en.2013-1358
PG 13
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 238HI
UT WOS:000325935200043
PM 23970786
ER
PT J
AU Sun, GH
Heimeier, RA
Fu, LZ
Hasebe, T
Das, B
Ishizuya-Oka, A
Shi, YB
AF Sun, Guihong
Heimeier, Rachel A.
Fu, Liezhen
Hasebe, Takashi
Das, Biswajit
Ishizuya-Oka, Atsuko
Shi, Yun-Bo
TI Expression Profiling of Intestinal Tissues Implicates Tissue-Specific
Genes and Pathways Essential for Thyroid Hormone-Induced Adult Stem Cell
Development
SO ENDOCRINOLOGY
LA English
DT Article
ID XENOPUS-LAEVIS TADPOLES; AMPHIBIAN METAMORPHOSIS; CONNECTIVE-TISSUE;
MICROARRAY DATA; POSTEMBRYONIC DEVELOPMENT; MATRIX-METALLOPROTEINASE;
BIOLOGICAL PATHWAYS; TR-ALPHA; EPITHELIUM; TOOL
AB The study of the epithelium during development in the vertebrate intestine touches upon many contemporary aspects of biology: to name a few, the formation of the adult stem cells (ASCs) essential for the life-long self-renewal and the balance of stem cell activity for renewal vs cancer development. Although extensive analyses have been carried out on the property and functions of the adult intestinal stem cells in mammals, little is known about their formation during development due to the difficulty of manipulating late-stage, uterus-enclosed embryos. The gastrointestinal tract of the amphibian Xenopus laevis is an excellent model system for the study of mammalian ASC formation, cell proliferation, and differentiation. During T-3-dependent amphibian metamorphosis, the digestive tract is extensively remodeled from the larval to the adult form for the adaptation of the amphibian from its aquatic herbivorous lifestyle to that of a terrestrial carnivorous frog. This involves de novo formation of ASCs that requires T-3 signaling in both the larval epithelium and nonepithelial tissues. To understand the underlying molecular mechanisms, we have characterized the gene expression profiles in the epithelium and nonepithelial tissues by using cDNA microarrays. Our results revealed that T-3 induces distinct tissue-specific gene regulation programs associated with the remodeling of the intestine, particularly the formation of the ASCs, and further suggested the existence of potentially many novel stem cell-associated genes, at least in the intestine during development.
C1 [Sun, Guihong] Wuhan Univ, Sch Basic Med Sci, Wuhan 430072, Peoples R China.
[Sun, Guihong; Heimeier, Rachel A.; Fu, Liezhen; Das, Biswajit; Shi, Yun-Bo] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Mol Morphogenesis, Program Cellular Regulat & Metab, NIH, Bethesda, MD 20892 USA.
[Hasebe, Takashi; Ishizuya-Oka, Atsuko] Nippon Med Sch, Dept Biol, Kawasaki, Kanagawa 2110063, Japan.
RP Shi, YB (reprint author), NICHHD, NIH, Lab Gene Regulat & Dev, Bldg 18T,Room 106,18 Library Dr,MSC 5431, Bethesda, MD 20892 USA.
EM heimeier781@gmail.com; a-oka@nms.ac.jp; shi@helix.nih.gov
FU intramural Research Program of National Institute of Child Health and
Human Development, National Institutes of Health; Narishige Zoological
Science Award
FX This work was supported by the intramural Research Program of National
Institute of Child Health and Human Development, National Institutes of
Health, and in part by Narishige Zoological Science Award (to T.H.).
NR 54
TC 11
Z9 11
U1 0
U2 8
PU ENDOCRINE SOC
PI WASHINGTON
PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA
SN 0013-7227
EI 1945-7170
J9 ENDOCRINOLOGY
JI Endocrinology
PD NOV
PY 2013
VL 154
IS 11
BP 4396
EP 4407
DI 10.1210/en.2013-1432
PG 12
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 238HI
UT WOS:000325935200047
PM 23970787
ER
PT J
AU Shimamura, M
Nakahara, M
Orim, F
Kurashige, T
Mitsutake, N
Nakashima, M
Kondo, S
Yamada, M
Taguchi, R
Kimura, S
Nagayama, Y
AF Shimamura, Mika
Nakahara, Mami
Orim, Florence
Kurashige, Tomomi
Mitsutake, Norisato
Nakashima, Masahiro
Kondo, Shinji
Yamada, Masanobu
Taguchi, Ryo
Kimura, Shioko
Nagayama, Yuji
TI Postnatal Expression of BRAF(V600E) Does Not Induce Thyroid Cancer in
Mouse Models of Thyroid Papillary Carcinoma
SO ENDOCRINOLOGY
LA English
DT Article
ID RET/PTC1 ONCOGENE; TRANSGENIC MICE; THYROTROPIN RECEPTOR; TARGETED
EXPRESSION; TUMOR INITIATION; PTEN LOSS; K-RAS; ACTIVATION; CELLS; BRAF
AB The mutant BRAF (BRAF(V600E)) is the most common genetic alteration in papillary thyroid carcinomas (PTCs). The oncogenicity of this mutation has been shown by some genetically engineered mouse models. However, in these mice, BRAF(V600E) is expressed in all the thyroid cells from the fetal periods, and suppresses thyroid function, thereby leading to TSH elevation, which by itself promotes thyroid tumorigenesis. To overcome these problems, we exploited 2 different approaches, both of which allowed temporally and spatially restricted expression of BRAF(V600E) in the thyroid glands. First, we generated conditional transgenic mice harboring the loxP-neo(R)-loxP-BRAF(V600E)-internal ribosome entry site-green fluorescent protein sequence [Tg(LNL-BRAF(V600E))]. The double transgenic mice (LNL-BRAF(V600E); TPO-Cre) were derived from a high expressor line of Tg(LNL-BRAF(V600E)) mice and TPO-Cre mice; the latter expresses Cre DNA recombinase under the control of thyroid-specific thyroid peroxidase (TPO) promoter and developed PTC-like lesions in early life under normal serum TSH levels due to mosaic recombination. In contrast, injection of adenovirus expressing Cre under the control of another thyroid-specific thyroglobulin (Tg) promoter (Ad-TgP-Cre) into the thyroids of LNL-BRAF(V600E) mice did not induce tumor formation despite detection of BRAF(V600E) and pERK in a small fraction of thyroid cells. Second, postnatal expression of BRAF(V600E) in a small number of thyroid cells was also achieved by injecting the lentivirus expressing loxP-green fluorescent protein-loxP-BRAF(V600E) into the thyroids of TPO-Cre mice; however, no tumor development was again observed. These results suggest that BRAF(V600E) does not appear to induce PTC-like lesions when expressed in a fraction of thyroid cells postnatally under normal TSH concentrations.
C1 [Shimamura, Mika; Nakahara, Mami; Kurashige, Tomomi; Nagayama, Yuji] Nagasaki Univ, Dept Mol Med, Atom Bomb Dis Inst, Nagasaki 8528523, Japan.
[Orim, Florence; Mitsutake, Norisato] Nagasaki Univ, Dept Radiat Med Sci, Atom Bomb Dis Inst, Nagasaki 8528523, Japan.
[Nakashima, Masahiro] Nagasaki Univ, Dept Tumor & Diagnost Pathol, Atom Bomb Dis Inst, Nagasaki 8528523, Japan.
[Kondo, Shinji] Nagasaki Univ, Dept Clin Pharmacol, Grad Sch Biomed Sci, Nagasaki 8528521, Japan.
[Yamada, Masanobu; Taguchi, Ryo] Gunma Univ, Dept Med & Mol Sci, Grad Sch Med, Maebashi, Gumma 3718511, Japan.
[Kimura, Shioko] NCI, Lab Metab, NIH, Bethesda, MD 20892 USA.
RP Nagayama, Y (reprint author), Nagasaki Univ, Dept Mol Med, Atom Bomb Dis Inst, Grad Sch Biomed Sci, 1-12-4 Sakamoto, Nagasaki 8528523, Japan.
EM nagayama@nagasaki-u.ac.jp
OI Mitsutake, Norisato/0000-0002-2744-8046
FU Japan Society for the Promotion of Science; Japan Thyroid Association
FX This study was supported, in part, by Grants-in-Aid for Scientific
Research from Japan Society for the Promotion of Science and by Japan
Thyroid Association.
NR 34
TC 8
Z9 8
U1 1
U2 6
PU ENDOCRINE SOC
PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0013-7227
EI 1945-7170
J9 ENDOCRINOLOGY
JI Endocrinology
PD NOV
PY 2013
VL 154
IS 11
BP 4423
EP 4430
DI 10.1210/en.2013-1174
PG 8
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 238HI
UT WOS:000325935200049
PM 23970782
ER
PT J
AU Dias, C
McDonald, A
Sincan, M
Rupps, R
Markello, T
Salvarinova, R
Santos, RF
Menghrajani, K
Ahaghotu, C
Sutherland, DP
Fortuno, ES
Kollmann, TR
Demos, M
Friedman, JM
Speert, DP
Gahl, WA
Boerkoel, CF
AF Dias, Cristina
McDonald, Allison
Sincan, Murat
Rupps, Rosemarie
Markello, Thomas
Salvarinova, Ramona
Santos, Rui F.
Menghrajani, Kamal
Ahaghotu, Chidi
Sutherland, Darren P.
Fortuno, Edgardo S., III
Kollmann, Tobias R.
Demos, Michelle
Friedman, Jan M.
Speert, David P.
Gahl, William A.
Boerkoel, Cornelius F.
TI Recurrent subacute post-viral onset of ataxia associated with a PRF1
mutation
SO EUROPEAN JOURNAL OF HUMAN GENETICS
LA English
DT Article
DE exome sequencing; neurodegeneration; cerebellar white matter; familial
hemophagocytic lymphohistiocytosis; interleukin-1 beta
ID FAMILIAL HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS; NERVOUS-SYSTEM INVOLVEMENT;
MULTIPLE-SCLEROSIS; CNS INVOLVEMENT; PERFORIN GENE; CHILDREN;
INFLAMMATION; FREQUENCY; SPECTRUM; DISEASE
AB Inflammation is an important contributor to pediatric and adult neurodegeneration. Understanding the genetic determinants of neuroinflammation provides valuable insight into disease mechanism. We characterize a disorder of recurrent immune-mediated neurodegeneration. We report two sisters who presented with neurodegeneration triggered by infections. The proband, a previously healthy girl, presented at 22.5 months with ataxia and dysarthria following mild gastroenteritis. MRI at onset showed a symmetric signal abnormality of the cerebellar and peritrigonal white matter. Following a progressive course of partial remissions and relapses, she died at 5 years of age. Her older sister had a similar course following varicella infection, she died within 13 months. Both sisters had unremarkable routine laboratory testing, with exception of a transient mild cytopenia in the proband 19 months after presentation. Exome sequencing identified a biallelic perforin1 mutation (PRF1; p. R225W) previously associated with familial hemophagocytic lymphohistiocytosis (FHL). In contrast to FHL, these girls did not have hematopathology or cytokine overproduction. However, 3 years after disease onset, the proband had markedly deficient interleukin-1 beta (IL-1 beta) production. These observations extend the spectrum of disease associated with perforin mutations to immune-mediated neurodegeneration triggered by infection and possibly due to primary immunodeficiency.
C1 [Dias, Cristina; Rupps, Rosemarie; Friedman, Jan M.; Boerkoel, Cornelius F.] Univ British Columbia, Dept Med Genet, Vancouver, BC V6H 3N1, Canada.
[Dias, Cristina; Rupps, Rosemarie; Friedman, Jan M.; Boerkoel, Cornelius F.] BC Childrens Hosp, Child & Family Res Inst, Vancouver, BC, Canada.
[McDonald, Allison; Sutherland, Darren P.; Fortuno, Edgardo S., III; Kollmann, Tobias R.; Speert, David P.] Child & Family Res Inst, Ctr Understanding & Preventing Infect Children, Vancouver, BC, Canada.
[McDonald, Allison; Sutherland, Darren P.; Fortuno, Edgardo S., III; Kollmann, Tobias R.; Speert, David P.] Univ British Columbia, Dept Pediat, Div Infect & Immunol Dis, Vancouver, BC V6H 3N1, Canada.
[Sincan, Murat; Markello, Thomas; Menghrajani, Kamal; Ahaghotu, Chidi; Gahl, William A.; Boerkoel, Cornelius F.] NIH, Undiagnosed Dis Program, Off Rare Dis Res, Bethesda, MD 20892 USA.
[Sincan, Murat; Markello, Thomas; Menghrajani, Kamal; Ahaghotu, Chidi; Gahl, William A.; Boerkoel, Cornelius F.] NHGRI, Bethesda, MD 20892 USA.
[Rupps, Rosemarie] Rare Dis Fdn, Vancouver, BC, Canada.
[Salvarinova, Ramona] Univ British Columbia, Dept Pediat, Div Biochem Dis, Vancouver, BC V6H 3N1, Canada.
[Santos, Rui F.] BC Childrens Hosp, Dept Radiol, Vancouver, BC, Canada.
[Santos, Rui F.] Univ British Columbia, Vancouver, BC V6H 3N1, Canada.
[Demos, Michelle] Univ British Columbia, Dept Pediat, Div Neurol, Vancouver, BC V6H 3N1, Canada.
RP Boerkoel, CF (reprint author), Univ British Columbia, Dept Med Genet, 4500 Oak St,C234, Vancouver, BC V6H 3N1, Canada.
EM cornelius.boerkoel@nih.gov
OI Friedman, Jan/0000-0002-7482-9570; Dias, Cristina/0000-0001-5411-4984
FU Intramural Research Program of the NHGRI; Rare Disease Foundation;
Canadian Institutes for Health Research; Canadian Child Health Clinician
Scientist Program; Child and Family Research Institute; University of
British Columbia
FX We are grateful to Dr Camilo Toro for manuscript review and critical
analysis, and acknowledge Drs Patrick Tang and Rusang Tan for their
collaboration. We would like to express a special thanks to the
patients' family. This study was primarily funded by the Intramural
Research Program of the NHGRI and in part by the Rare Disease
Foundation. Funding was supplied by the Canadian Institutes for Health
Research (DPS). DPS is the Sauder Family Professor of Pediatric
Infectious Diseases. CD is supported by the Canadian Child Health
Clinician Scientist Program and the Child and Family Research Institute.
AM is supported by the University of British Columbia.
NR 44
TC 5
Z9 5
U1 0
U2 4
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1018-4813
EI 1476-5438
J9 EUR J HUM GENET
JI Eur. J. Hum. Genet.
PD NOV
PY 2013
VL 21
IS 11
BP 1232
EP 1239
DI 10.1038/ejhg.2013.20
PG 8
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 237IC
UT WOS:000325861500010
PM 23443029
ER
PT J
AU Szu, SC
AF Szu, Shousun Chen
TI Development of Vi conjugate - a new generation of typhoid vaccine
SO EXPERT REVIEW OF VACCINES
LA English
DT Review
DE infants; typhoid fever; vaccine development; Vi conjugate; young
children
ID INFLUENZAE TYPE-B; CAPSULAR POLYSACCHARIDE CONJUGATE; 2-TO 4-YEAR-OLD
CHILDREN; STANDARD REFERENCE SERUM; ENTERICA SEROVAR TYPHI; IGG ANTI-VI;
SALMONELLA-TYPHI; HAEMOPHILUS-INFLUENZAE; MULTIDRUG-RESISTANT;
STREPTOCOCCUS-PNEUMONIAE
AB Typhoid fever remains to be a serious disease burden worldwide with an estimated annual incidence about 20 million. The licensed vaccines showed moderate protections and have multiple deficiencies. Most important of all, none of the licensed typhoid vaccines demonstrated protection for children under 5 years old. These limitations impeded successful implementation of typhoid vaccination programs. To improve immunogenicity Vi was conjugated to rEPA, a recombinant exoprotein A from Pseudomonas aeruginosa. Vi-rEPA showed higher and longer lasting anti-Vi IgG in adults and children than Vi alone in high endemic areas. In school-age children and adults, the immunity persisted more than 8 years. In a double-blind, placebo-controlled and randomized efficacy trial in 2- to 5-year-old children, Vi-rEPA conferred 89% protective efficacy against typhoid fever and the protection lasted at least 4 years. When given concomitantly with infant routine vaccines, Vi-rEPA was safe, immunogenic and showed no interference with the routine vaccines. Vi conjugate vaccine was also attempted and successfully demonstrated by several other laboratories and manufactures. Using either rEPA or different carrier proteins, such as diphtheria or tetanus toxoid, recombinant diphtheria toxin (CRM197), the Vi conjugates synthesized was significantly more immunogenic than Vi alone. Recently, two Vi-tetanus toxoid conjugates were licensed in India for all ages, starts as young as 3 month old. This new generation of typhoid vaccine opens up a new era for typhoid prevention and elimination.
C1 Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20814 USA.
RP Szu, SC (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, 9402 Wildoak Dr, Bethesda, MD 20814 USA.
EM SzuNIH@gmail.com
FU NIH; NIH, Eunice Kennedy Shriver National Institute of Child Health and
Human Development
FX This research was supported by the Intramural Research Program of the
NIH, Eunice Kennedy Shriver National Institute of Child Health and Human
Development. The author has no other relevant affiliations or financial
involvement with any organization or entity with a financial interest in
or financial conflict with the subject matter or materials discussed in
the manuscript apart from those disclosed.
NR 99
TC 23
Z9 23
U1 2
U2 18
PU EXPERT REVIEWS
PI LONDON
PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB,
ENGLAND
SN 1476-0584
EI 1744-8395
J9 EXPERT REV VACCINES
JI Expert Rev. Vaccines
PD NOV
PY 2013
VL 12
IS 11
BP 1273
EP 1286
DI 10.1586/14760584.2013.845529
PG 14
WC Immunology
SC Immunology
GA 240OD
UT WOS:000326105500007
PM 24156285
ER
PT J
AU Hutter, CM
Mechanic, LE
Chatterjee, N
Kraft, P
Gillanders, EM
AF Hutter, Carolyn M.
Mechanic, Leah E.
Chatterjee, Nilanjan
Kraft, Peter
Gillanders, Elizabeth M.
CA NCI Gene-Environm Think Tank
TI Gene-Environment Interactions in Cancer Epidemiology: A National Cancer
Institute Think Tank Report
SO GENETIC EPIDEMIOLOGY
LA English
DT Review
DE gene-environment interactions; complex phenotypes; genetic epidemiology
ID GENOME-WIDE ASSOCIATION; SAMPLE-SIZE REQUIREMENTS; MULTIPLE
SUSCEPTIBILITY LOCI; NAT2 SLOW ACETYLATION; BODY-MASS INDEX;
BLADDER-CANCER; BREAST-CANCER; COMPLEX DISEASES; STATISTICAL
INTERACTIONS; MOLECULAR EPIDEMIOLOGY
AB Cancer risk is determined by a complex interplay of genetic and environmental factors. Genome-wide association studies (GWAS) have identified hundreds of common (minor allele frequency [MAF] > 0.05) and less common (0.01 < MAF < 0.05) genetic variants associated with cancer. The marginal effects of most of these variants have been small (odds ratios: 1.1-1.4). There remain unanswered questions on how best to incorporate the joint effects of genes and environment, including gene-environment (G x E) interactions, into epidemiologic studies of cancer. To help address these questions, and to better inform research priorities and allocation of resources, the National Cancer Institute sponsored a Gene-Environment Think Tank on January 10-11, 2012. The objective of the Think Tank was to facilitate discussions on (1) the state of the science, (2) the goals of G x E interaction studies in cancer epidemiology, and (3) opportunities for developing novel study designs and analysis tools. This report summarizes the Think Tank discussion, with a focus on contemporary approaches to the analysis of G x E interactions. Selecting the appropriate methods requires first identifying the relevant scientific question and rationale, with an important distinction made between analyses aiming to characterize the joint effects of putative or established genetic and environmental factors and analyses aiming to discover novel risk factors or novel interaction effects. Other discussion items include measurement error, statistical power, significance, and replication. Additional designs, exposure assessments, and analytical approaches need to be considered as we move from the current small number of success stories to a fuller understanding of the interplay of genetic and environmental factors.
C1 [Hutter, Carolyn M.; Mechanic, Leah E.; Gillanders, Elizabeth M.] NCI, Epidemiol & Genom Res Program, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA.
[Chatterjee, Nilanjan] NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Kraft, Peter] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
RP Hutter, CM (reprint author), NCI, Host Susceptibil Factors Branch, Epidemiol & Genom Res Program, Div Canc Control & Populat Sci, 9609 Med Ctr Dr,Room 4E232,MSC 9763, Bethesda, MD 20892 USA.
EM huttercm@mail.nih.gov
RI Abnet, Christian/C-4111-2015
OI Abnet, Christian/0000-0002-3008-7843
FU Intramural NIH HHS [Z99 CA999999]; NCI NIH HHS [P30 CA016672]
NR 142
TC 27
Z9 27
U1 3
U2 40
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 2013
VL 37
IS 7
BP 643
EP 657
DI 10.1002/gepi.21756
PG 15
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA 238VW
UT WOS:000325980600001
PM 24123198
ER
PT J
AU Fan, RZ
Wang, YF
Mills, JL
Wilson, AF
Bailey-Wilson, JE
Xiong, MM
AF Fan, Ruzong
Wang, Yifan
Mills, James L.
Wilson, Alexander F.
Bailey-Wilson, Joan E.
Xiong, Momiao
TI Functional Linear Models for Association Analysis of Quantitative Traits
SO GENETIC EPIDEMIOLOGY
LA English
DT Article
DE rare variants; common variants; association mapping; quantitative trait
loci; complex traits; functional data analysis
ID RARE VARIANTS; SEQUENCING ASSOCIATION; COMMON DISEASES; REGRESSION;
TESTS; SIMILARITY; STRATEGIES
AB Functional linear models are developed in this paper for testing associations between quantitative traits and genetic variants, which can be rare variants or common variants or the combination of the two. By treating multiple genetic variants of an individual in a human population as a realization of a stochastic process, the genome of an individual in a chromosome region is a continuum of sequence data rather than discrete observations. The genome of an individual is viewed as a stochastic function that contains both linkage and linkage disequilibrium (LD) information of the genetic markers. By using techniques of functional data analysis, both fixed and mixed effect functional linear models are built to test the association between quantitative traits and genetic variants adjusting for covariates. After extensive simulation analysis, it is shown that the F-distributed tests of the proposed fixed effect functional linear models have higher power than that of sequence kernel association test (SKAT) and its optimal unified test (SKAT-O) for three scenarios in most cases: (1) the causal variants are all rare, (2) the causal variants are both rare and common, and (3) the causal variants are common. The superior performance of the fixed effect functional linear models is most likely due to its optimal utilization of both genetic linkage and LD information of multiple genetic variants in a genome and similarity among different individuals, while SKAT and SKAT-O only model the similarities and pairwise LD but do not model linkage and higher order LD information sufficiently. In addition, the proposed fixed effect models generate accurate type I error rates in simulation studies. We also show that the functional kernel score tests of the proposed mixed effect functional linear models are preferable in candidate gene analysis and small sample problems. The methods are applied to analyze three biochemical traits in data from the Trinity Students Study.
C1 [Fan, Ruzong; Wang, Yifan] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biostat & Bioinformat Branch, Div Intramural Populat Hlth Res, NIH, Rockville, MD 20852 USA.
[Mills, James L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Intramural Populat Hlth Res, NIH, Rockville, MD 20852 USA.
[Wilson, Alexander F.; Bailey-Wilson, Joan E.] NHGRI, Inherited Dis Res Branch, NIH, Bethesda, MD 20892 USA.
[Xiong, Momiao] Univ Texas Houston, Human Genet Ctr, Houston, TX USA.
RP Fan, RZ (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biostat & Bioinformat Branch, Div Intramural Populat Hlth Res, 6100 Execut Blvd,Room 7B07J,MSC 7510, Rockville, MD 20852 USA.
EM fanr@mail.nih.gov
OI Bailey-Wilson, Joan/0000-0002-9153-2920
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development, National Institutes of Health, Maryland
FX We greatly thank the Trinity Students Study groups for letting us
analyze the data and using it as an example. This study was supported by
the Intramural Research Program of the Eunice Kennedy Shriver National
Institute of Child Health and Human Development, National Institutes of
Health, Maryland (Ruzong Fan, Yifan Wang, and James L. Mills).
NR 49
TC 22
Z9 22
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 2013
VL 37
IS 7
BP 726
EP 742
DI 10.1002/gepi.21757
PG 17
WC Genetics & Heredity; Mathematical & Computational Biology
SC Genetics & Heredity; Mathematical & Computational Biology
GA 238VW
UT WOS:000325980600009
PM 24130119
ER
PT J
AU Dasgeb, B
Kainerstorfer, J
Mehregan, D
Van Vreede, A
Gandjbakhche, A
AF Dasgeb, Bahar
Kainerstorfer, Jana
Mehregan, Darius
Van Vreede, Anthony
Gandjbakhche, Amir
TI An introduction to primary skin imaging
SO INTERNATIONAL JOURNAL OF DERMATOLOGY
LA English
DT Review
ID OPTICAL COHERENCE TOMOGRAPHY; REFLECTANCE CONFOCAL MICROSCOPY; IN-VIVO;
MELANOCYTIC LESIONS; ULTRASOUND; MELANOMA; DIAGNOSIS; ULTRASONOGRAPHY;
ELASTOGRAPHY; CRITERIA
AB Dermatology is a field in which clinical examination is heavily relied upon for diagnosis. When required, a tissue biopsy may also be performed to confirm the diagnosis. Recent advances in imaging techniques have been applied to cutaneous lesions to improve diagnostic accuracy without the need for biopsy. These new imaging techniques are reviewed for their developing role in dermatology.
C1 [Dasgeb, Bahar] Mem Sloan Kettering Canc Ctr, Dept Dermatol, New York, NY 10021 USA.
[Mehregan, Darius; Van Vreede, Anthony] Wayne State Univ, Dept Dermatol, Detroit, MI USA.
[Dasgeb, Bahar; Kainerstorfer, Jana; Gandjbakhche, Amir] NICHD, Analyt & Stochast Biomed Phys Sect, NIH, Bethesda, MD USA.
[Mehregan, Darius] Pinkus Dermatopathol Labs, Monroe, MI USA.
RP Van Vreede, A (reprint author), 5057 Woodward Ave 3101, Detroit, MI 48202 USA.
EM avanvree@med.wayne.edu
NR 49
TC 4
Z9 4
U1 2
U2 13
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0011-9059
EI 1365-4632
J9 INT J DERMATOL
JI Int. J. Dermatol.
PD NOV
PY 2013
VL 52
IS 11
BP 1319
EP 1330
DI 10.1111/ijd.12048
PG 12
WC Dermatology
SC Dermatology
GA 239WP
UT WOS:000326056900001
PM 23879559
ER
PT J
AU Fernando, J
Faber, TW
Pullen, NA
Falanga, YT
Kolawole, EM
Oskeritzian, CA
Barnstein, BO
Bandara, G
Li, GQ
Schwartz, LB
Spiegel, S
Straus, DB
Conrad, DH
Bunting, KD
Ryan, JJ
AF Fernando, Josephine
Faber, Travis W.
Pullen, Nicholas A.
Falanga, Yves T.
Kolawole, Elizabeth Motunrayo
Oskeritzian, Carole A.
Barnstein, Brian O.
Bandara, Geethani
Li, Geqiang
Schwartz, Lawrence B.
Spiegel, Sarah
Straus, David B.
Conrad, Daniel H.
Bunting, Kevin D.
Ryan, John J.
TI Genotype-Dependent Effects of TGF-beta 1 on Mast Cell Function:
Targeting the Stat5 Pathway
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID GROWTH-FACTOR-BETA; FC-EPSILON-RI; NECROSIS-FACTOR-ALPHA; TGF-BETA;
CYTOKINE PRODUCTION; T-CELLS; ALLERGIC RESPONSES; SIGNAL TRANSDUCER;
GENE-EXPRESSION; TRANSCRIPTION 5
AB We previously demonstrated that TGF-beta 1 suppresses IgE-mediated signaling in human and mouse mast cells in vitro, an effect that correlated with decreased expression of the high-affinity IgE receptor, Fc epsilon RI. The in vivo effects of TGF-beta 1 and the means by which it suppresses mast cells have been less clear. This study shows that TGF-beta 1 suppresses Fc epsilon RI and c-Kit expression in vivo. By examining changes in cytokine production concurrent with Fc epsilon RI expression, we found that TGF-beta 1 suppresses TNF production independent of Fc epsilon RI levels. Rather, IgE-mediated signaling was altered. TGF-beta 1 significantly reduced expression of Fyn and Stat5, proteins critical for cytokine induction. These changes may partly explain the effects of TGF-beta 1, because Stat5B overexpression blocked TGF-mediated suppression of IgE-induced cytokine production. We also found that Stat5B is required for mast cell migration toward stem cell factor, and that TGF-beta 1 reduced this migration. We found evidence that genetic background may alter TGF responses. TGF-beta 1 greatly reduced mast cell numbers in Th1-prone C57BL/6, but not Th2-prone 129/Sv mice. Furthermore, TGF-beta 1 did not suppress IgE-induced cytokine release and did increase c-Kit-mediated migration in 129/Sv mast cells. These data correlated with high basal Fyn and Stat5 expression in 129/Sv cells, which was not reduced by TGF-beta 1 treatment. Finally, primary human mast cell populations also showed variable sensitivity to TGF-beta 1-mediated changes in Stat5 and IgE-mediated IL-6 secretion. We propose that TGF-beta 1 regulates mast cell homeostasis, and that this feedback suppression may be dependent on genetic context, predisposing some individuals to atopic disease.
C1 [Fernando, Josephine; Faber, Travis W.; Pullen, Nicholas A.; Falanga, Yves T.; Kolawole, Elizabeth Motunrayo; Barnstein, Brian O.; Straus, David B.; Ryan, John J.] Virginia Commonwealth Univ, Dept Biol, Richmond, VA 23284 USA.
[Oskeritzian, Carole A.; Spiegel, Sarah] Virginia Commonwealth Univ, Dept Biochem & Mol Biol, Richmond, VA 23298 USA.
[Oskeritzian, Carole A.; Spiegel, Sarah] NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA.
[Li, Geqiang] Harvard Univ, Boston Childrens Hosp, Boston, MA 02115 USA.
[Schwartz, Lawrence B.] Virginia Commonwealth Univ, Dept Internal Med, Richmond, VA 23298 USA.
[Conrad, Daniel H.] Virginia Commonwealth Univ, Dept Microbiol & Immunol, Richmond, VA 23298 USA.
[Bunting, Kevin D.] Childrens Healthcare Atlanta, Aflac Canc & Blood Disorders Ctr, Dept Pediat, Atlanta, GA 30322 USA.
[Bunting, Kevin D.] Emory Univ, Atlanta, GA 30322 USA.
RP Ryan, JJ (reprint author), Virginia Commonwealth Univ, Dept Biol, Box 842012, Richmond, VA 23284 USA.
EM jjryan@vcu.edu
FU National Institutes of Health [1R01AI59638, U19AI077435, 2R01DK059380,
K01AR053186, 1R01AI095494]
FX This work was supported by National Institutes of Health Grants
1R01AI59638 (to J.J.R.), U19AI077435 (to J.J.R., S. S., and D. H. C.),
2R01DK059380 (to K. D. B.), K01AR053186 (to C.A.O.), and 1R01AI095494
(to C.A.O.).
NR 66
TC 8
Z9 8
U1 0
U2 0
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
EI 1550-6606
J9 J IMMUNOL
JI J. Immunol.
PD NOV 1
PY 2013
VL 191
IS 9
BP 4505
EP 4513
DI 10.4049/jimmunol.1202723
PG 9
WC Immunology
SC Immunology
GA 238FS
UT WOS:000325929000007
PM 24068671
ER
PT J
AU McPhee, CG
Bubier, JA
Sproule, TJ
Park, G
Steinbuck, MP
Schott, WH
Christianson, GJ
Morse, HC
Roopenian, DC
AF McPhee, Caroline G.
Bubier, Jason A.
Sproule, Thomas J.
Park, Giljun
Steinbuck, Martin P.
Schott, William H.
Christianson, Gregory J.
Morse, Herbert C., III
Roopenian, Derry C.
TI IL-21 Is a Double-Edged Sword in the Systemic Lupus Erythematosus-like
Disease of BXSB.Yaa Mice
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID HELPER T-CELLS; GERMINAL CENTER RESPONSES; B-CELLS; BCL-6 EXPRESSION;
MURINE LUPUS; YAA MICE; AUTOIMMUNITY; INTERLEUKIN-21; GENERATION;
RECEPTOR
AB The pleiotropic cytokine IL-21 is implicated in the pathogenesis of human systemic lupus erythematosus by polymorphisms in the molecule and its receptor (IL-21R). The systemic lupus erythematosus-like autoimmune disease of BXSB.Yaa mice is critically dependent on IL-21 signaling, providing a model for understanding IL-21/IL-21R signaling in lupus pathogenesis. In this study, we generated BXSB.Yaa mice selectively deficient in IL-21R on B cells, on all T cells, or on CD8(+) T cells alone and examined the effects on disease. We found that IL-21 signaling to B cells is essential for the development of all classical disease manifestations, but that IL-21 signaling also supports the expansion of central memory, CD8(+) suppressor cells and broadly represses the cytokine activity of CD4(+) T cells. These results indicate that IL-21 has both disease-promoting and disease-suppressive effects in the autoimmune disease of BXSB.Yaa mice.
C1 [McPhee, Caroline G.; Bubier, Jason A.; Sproule, Thomas J.; Park, Giljun; Steinbuck, Martin P.; Schott, William H.; Christianson, Gregory J.; Roopenian, Derry C.] Jackson Lab, Bar Harbor, ME 04609 USA.
[Morse, Herbert C., III] NIAID, Lab Immunogenet, NIH, Rockville, MD 20852 USA.
RP Roopenian, DC (reprint author), Jackson Lab, 600 Main St, Bar Harbor, ME 04609 USA.
EM hmorse@niaid.nih.gov; dcr@jax.org
OI Morse, Herbert/0000-0002-9331-3705; Bubier, Jason/0000-0001-5013-1234
FU Intramural Research Program of the National Institutes of Health,
National Institute of Allergy and Infectious Diseases; Alliance for
Lupus Research; National Institutes of Health; Arthritis Foundation
FX This work was supported in part by the Intramural Research Program of
the National Institutes of Health, National Institute of Allergy and
Infectious Diseases (to H. C. M.) and by the Alliance for Lupus Research
(to D. C. R.). C. G. M. was supported in part by a National Institutes
of Health Training Grant. J.A.B. was supported by the Arthritis
Foundation.
NR 47
TC 19
Z9 19
U1 0
U2 2
PU AMER ASSOC IMMUNOLOGISTS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0022-1767
EI 1550-6606
J9 J IMMUNOL
JI J. Immunol.
PD NOV 1
PY 2013
VL 191
IS 9
BP 4581
EP 4588
DI 10.4049/jimmunol.1300439
PG 8
WC Immunology
SC Immunology
GA 238FS
UT WOS:000325929000015
PM 24078696
ER
PT J
AU Raetz, M
Kibardin, A
Sturge, CR
Pifer, R
Li, HY
Burstein, E
Ozato, K
Larin, S
Yarovinsky, F
AF Raetz, Megan
Kibardin, Alexey
Sturge, Carolyn R.
Pifer, Reed
Li, Haiying
Burstein, Ezra
Ozato, Keiko
Larin, Sergey
Yarovinsky, Felix
TI Cooperation of TLR12 and TLR11 in the IRF8-Dependent IL-12 Response to
Toxoplasma gondii Profilin
SO JOURNAL OF IMMUNOLOGY
LA English
DT Article
ID TOLL-LIKE RECEPTORS; CD8-ALPHA(+) DENDRITIC CELLS; SINGLE-STRANDED RNA;
SUBCELLULAR-LOCALIZATION; INTRACELLULAR PARASITE; INTERFERON-GAMMA;
CUTTING EDGE; INTERLEUKIN-12; RECOGNITION; RESISTANCE
AB TLRs play a central role in the innate recognition of pathogens and the activation of dendritic cells (DCs). In this study, we establish that, in addition to TLR11, TLR12 recognizes the profilin protein of the protozoan parasite Toxoplasma gondii and regulates IL-12 production by DCs in response to the parasite. Similar to TLR11, TLR12 is an endolysosomal innate immune receptor that colocalizes and interacts with UNC93B1. Biochemical experiments revealed that TLR11 and TLR12 directly bind to T. gondii profilin and are capable of forming a heterodimer complex. We also establish that the transcription factor IFN regulatory factor 8, not NF-kappa B, plays a central role in the regulation of the TLR11- and TLR12-dependent IL-12 response of DCs. These results suggest a central role for IFN regulatory factor 8-expressing CD8(+) DCs in governing the TLR11- and TLR12-mediated host defense against T. gondii.
C1 [Raetz, Megan; Sturge, Carolyn R.; Pifer, Reed; Yarovinsky, Felix] Univ Texas SW Med Ctr Dallas, Dept Immunol, Dallas, TX 75390 USA.
[Kibardin, Alexey; Larin, Sergey] Russian Acad Sci, Inst Gene Biol, Gene Therapy Lab, Moscow 119334, Russia.
[Li, Haiying; Burstein, Ezra] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Dallas, TX 75390 USA.
[Ozato, Keiko] NICHHD, NIH, Program Genom Differentiat, Bethesda, MD 20892 USA.
[Larin, Sergey] Fed Res Ctr Pediat Hematol Oncol & Immunol, Moscow 117198, Russia.
[Larin, Sergey] Moscow Inst Phys & Technol, Moscow 141700, Russia.
RP Yarovinsky, F (reprint author), Univ Texas SW Med Ctr Dallas, Dept Immunol, 5323 Harry Hines Blvd, Dallas, TX 75390 USA.
EM Felix.Yarovinsky@UTSouthwestern.edu
RI Burstein, Ezra/B-7247-2016
OI Burstein, Ezra/0000-0003-4341-6367
FU National Institutes of Health [A1-085263, AI079371]; Burroughs Wellcome
Foundation
FX This work was supported by National Institutes of Health Grants
A1-085263 and AI079371 (to F. Y.), as well as by a Burroughs Wellcome
Foundation Investigators in the Pathogenesis of Infectious Diseases
award (to F.Y.).
NR 52
TC 25
Z9 31
U1 1
U2 13
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 2013
VL 191
IS 9
BP 4818
EP 4827
DI 10.4049/jimmunol.1301301
PG 10
WC Immunology
SC Immunology
GA 238FS
UT WOS:000325929000038
PM 24078692
ER
PT J
AU Giddings, LA
Newman, DJ
AF Giddings, Lesley-Ann
Newman, David J.
TI Microbial natural products: molecular blueprints for antitumor drugs
SO JOURNAL OF INDUSTRIAL MICROBIOLOGY & BIOTECHNOLOGY
LA English
DT Review
DE Microbial natural product; Microbial genome; Cancer drugs; Clinical
trial
ID HISTONE-DEACETYLASE INHIBITORS; PHASE-II TRIAL; TUNICATE
ECTEINASCIDIA-TURBINATA; TRANSFORMED-CELL DIFFERENTIATION;
MICROTUBULE-STABILIZING AGENTS; SALINOSPORAMIDE-A NPI-0052; BIOSYNTHETIC
GENE CLUSTERS; MOLLUSK ELYSIA-RUFESCENS; KAHALALIDE-F; PROTEASOME
INHIBITOR
AB Microbes from two of the three domains of life, the Prokarya, and Eukarya, continue to serve as rich sources of structurally complex chemical scaffolds that have proven to be essential for the development of anticancer therapeutics. This review describes only a handful of exemplary natural products and their derivatives as well as those that have served as elegant blueprints for the development of novel synthetic structures that are either currently in use or in clinical or preclinical trials together with some of their earlier analogs in some cases whose failure to proceed aided in the derivation of later compounds. In every case, a microbe has been either identified as the producer of secondary metabolites or speculated to be involved in the production via symbiotic associations. Finally, rapidly evolving next-generation sequencing technologies have led to the increasing availability of microbial genomes. Relevant examples of genome mining and genetic manipulation are discussed, demonstrating that we have only barely scratched the surface with regards to harnessing the potential of microbes as sources of new pharmaceutical leads/agents or biological probes.
C1 [Giddings, Lesley-Ann; Newman, David J.] Frederick Natl Lab Canc Res, Nat Prod Branch, Dev Therapeut Program, DCTD, Frederick, MD 21702 USA.
RP Giddings, LA (reprint author), Frederick Natl Lab Canc Res, Nat Prod Branch, Dev Therapeut Program, DCTD, POB B, Frederick, MD 21702 USA.
EM Lesley-Ann.Giddings@nih.gov; dn22a@nih.gov
NR 243
TC 14
Z9 15
U1 4
U2 72
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 1367-5435
EI 1476-5535
J9 J IND MICROBIOL BIOT
JI J. Ind. Microbiol. Biotechnol.
PD NOV
PY 2013
VL 40
IS 11
BP 1181
EP 1210
DI 10.1007/s10295-013-1331-1
PG 30
WC Biotechnology & Applied Microbiology
SC Biotechnology & Applied Microbiology
GA 237DG
UT WOS:000325847800001
PM 23999966
ER
PT J
AU Chaemsaithong, P
Romero, R
Korzeniewski, SJ
Schwartz, AG
Stampalija, T
Dong, Z
Yeo, L
Hernandez-Andrade, E
Hassan, SS
Chaiworapongsa, T
AF Chaemsaithong, Piya
Romero, Roberto
Korzeniewski, Steven J.
Schwartz, Alyse G.
Stampalija, Tamara
Dong, Zhong
Yeo, Lami
Hernandez-Andrade, Edgar
Hassan, Sonia S.
Chaiworapongsa, Tinnakorn
TI Soluble TRAIL in normal pregnancy and acute pyelonephritis: a potential
explanation for the susceptibility of pregnant women to microbial
products and infection
SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE
LA English
DT Article
DE Innate immunity; neutrophil apoptosis; non-pregnant; normal pregnancy;
plasma; tumor necrosis factor-related apoptosis-inducing ligand
ID APOPTOSIS-INDUCING LIGAND; INFLAMMATORY RESPONSE SYNDROME;
POLYMORPHONUCLEAR NEUTROPHIL ACTIVATION; INTRAUTERINE GROWTH
RESTRICTION; RESPIRATORY-DISTRESS SYNDROME; URINARY-TRACT INFECTIONS;
FADD-DEPENDENT APOPTOSIS; NF-KAPPA-B; METABOLIC CHARACTERISTICS; DEATH
DOMAIN
AB Objective: Pregnancy is characterized by activation of the innate immune response demonstrated by phenotypic and metabolic changes in granulocytes and monocytes. This state of activation has been implicated in the pathophysiology of multiorgan dysfunction of pregnant women with acute viral or bacterial infection. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is one of the mediators responsible for neutrophil apoptosis. Gene deletion of TRAIL results in delayed neutrophil apoptosis and resolution of inflammation after the administration of bacterial endotoxin. The aim of this study was to determine whether maternal plasma concentrations of the soluble form of TRAIL (sTRAIL) differ in women with uncomplicated pregnancy and those with acute pyelonephritis.
Method: A cross-sectional study was conducted to include women in the following groups: (1) non-pregnant (n = 23); (2) uncomplicated pregnancies (n = 93) and (3) pregnancies with acute pyelonephritis (n = 23). Plasma concentrations of sTRAIL were determined by enzyme-linked immunoassay.
Results: (1) Women with uncomplicated pregnancies had a lower mean plasma sTRAIL concentration (pg/mL) than non-pregnant women (31.5 +/- 10.1 versus 53.3 +/- 12.5; p<0.001); (2) plasma sTRAIL concentrations did not change as a function of gestational age (Pearson correlation = -0.1; p = 0.4); (3) the mean plasma sTRAIL concentration (pg/mL) was significantly lower in pregnant women with acute pyelonephritis than in those with uncomplicated pregnancies (20.5 +/- 6.6 versus 31.5 +/- 10.1; p<0.001) and (4) among patients with acute pyelonephritis, patients with bacteremia had a significantly lower mean plasma concentration of sTRAIL (pg/mL) than those without bacteremia (15.1 +/- 4.8 versus 24.7 +/- 4.6; p<0.001).
Conclusion: Women with uncomplicated pregnancies are associated with a significantly lower mean maternal plasma concentration of sTRAIL than that observed in non-pregnant women. Moreover, a further decrease in plasma sTRAIL concentration was observed in pregnant women with acute pyelonephritis, and this could account, at least in part, for the exaggerated intravascular inflammatory response previously reported in pyelonephritis during pregnancy.
C1 [Chaemsaithong, Piya; Romero, Roberto; Korzeniewski, Steven J.; Schwartz, Alyse G.; Stampalija, Tamara; Dong, Zhong; Yeo, Lami; Hernandez-Andrade, Edgar; Hassan, Sonia S.; Chaiworapongsa, Tinnakorn] NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA.
[Chaemsaithong, Piya; Romero, Roberto; Korzeniewski, Steven J.; Schwartz, Alyse G.; Stampalija, Tamara; Dong, Zhong; Yeo, Lami; Hernandez-Andrade, Edgar; Hassan, Sonia S.; Chaiworapongsa, Tinnakorn] NICHD, Perinatol Res Branch, NIH, DHHS, Detroit, MI USA.
[Korzeniewski, Steven J.; Schwartz, Alyse G.; Yeo, Lami; Hernandez-Andrade, Edgar; Hassan, Sonia S.; Chaiworapongsa, Tinnakorn] Wayne State Univ, Dept Obstet & Gynecol, Sch Med, Detroit, MI 48201 USA.
[Stampalija, Tamara] IRCCS Burlo Garofolo, Inst Maternal & Child Hlth, Trieste, IT, Italy.
RP Romero, R (reprint author), Wayne State Univ, NICHD, DHHS, Perinatol Res Branch,Hutzel Womens Hosp,NIH, 3990 John R,Box 4, Detroit, MI 48201 USA.
EM romeror@mail.nih.gov
RI Stampalija, Tamara/K-4900-2014
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development, National Institutes of Health, Department of Health and
Human Services [HHSN275201300006C]
FX The authors report no declarations of interest. This project has been
funded in whole or in part with Federal funds from the Eunice Kennedy
Shriver National Institute of Child Health and Human Development,
National Institutes of Health, Department of Health and Human Services,
under Contract No. HHSN275201300006C.
NR 107
TC 2
Z9 3
U1 0
U2 3
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1476-7058
EI 1476-4954
J9 J MATERN-FETAL NEO M
JI J. Matern.-Fetal Neonatal Med.
PD NOV
PY 2013
VL 26
IS 16
BP 1568
EP 1575
DI 10.3109/14767058.2013.783811
PG 8
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 238YP
UT WOS:000325988600002
PM 23480056
ER
PT J
AU Rahimi, Z
Ahmadi, R
Vaisi-Raygani, A
Rahimi, Z
Bahrehmand, F
Parsian, A
AF Rahimi, Zohreh
Ahmadi, Reza
Vaisi-Raygani, Asad
Rahimi, Ziba
Bahrehmand, Fariborz
Parsian, Abbas
TI Butyrylcholinesterase (BChE) activity is associated with the risk of
preeclampsia: influence on lipid and lipoprotein metabolism and
oxidative stress
SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE
LA English
DT Article
DE AOPE genotype; BChE activity; MDA; preeclampsia; TAC
ID SERUM BUTYRYLCHOLINESTERASE; WESTERN IRAN; ANTIOXIDANT STATUS;
DIABETES-MELLITUS; PREGNANCY; WOMEN; ALLELES; PROFILE;
PSEUDOCHOLINESTERASE; PEROXIDATION
AB Objective: To determine the butyrylcholinesterase (BChE) activity and phenotypes in preeclampsia and its possible association with lipid and lipoprotein metabolism and oxidative stress in preeclamptic women.
Methods: In a case-control study, 101 pregnant women with normal pregnancy and 198 women with preeclampsia from Western Iran were studied. The serum BChE activity and phenotypes were measured using spectrophotometric method. The apolipoprotein E (APOE) genotypes were identified using PCR-RFLP. The serum malondialdehyde (MDA) level and total antioxidant capacity (TAC) were determined by HPLC and commercial kits, respectively.
Results: The BChE activity and the frequency of non-usual BChE phenotype in preeclamptic women were significantly lower and higher, respectively compared to controls. There was a higher BChE activity in the presence of APOE epsilon 3 epsilon 4 compared to epsilon 3 epsilon 3 genotype in preeclamptic women. In addition, there were significant positive correlations between BChE activity and the levels of low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, total cholesterol (TC) and TAC. However, there was a negative but significant correlation between BChE activity and MDA level.
Conclusions: Our study for the first time indicated that BChE activity might be involved in the pathogenesis of preeclampsia through influence on lipid and lipoprotein metabolism and oxidative stress.
C1 [Rahimi, Zohreh; Rahimi, Ziba] Kermanshah Univ Med Sci, Med Biol Res Ctr, Kermanshah, Iran.
[Rahimi, Zohreh; Ahmadi, Reza; Vaisi-Raygani, Asad; Bahrehmand, Fariborz] Kermanshah Univ Med Sci, Sch Med, Dept Biochem, Kermanshah, Iran.
[Parsian, Abbas] NIAAA, Div Neurosci & Behav, NIH, Rockville, MD 20852 USA.
RP Rahimi, Z (reprint author), Sch Med, Med Biol Res Ctr, Daneshgah Ave, Kermanshah 6714869914, Iran.
EM zrahimi@kums.ac.ir
OI Rahimi, Zohreh/0000-0001-7589-3307; Vaisi-Raygani,
Asad/0000-0002-3042-2832
FU Kermanshah University of Medical Sciences, Kermanshah, Iran
FX This work was financially supported by a grant from Vice Chancellor for
Research of Kermanshah University of Medical Sciences, Kermanshah, Iran.
The authors report no declarations of interest.
NR 29
TC 4
Z9 4
U1 0
U2 5
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1476-7058
EI 1476-4954
J9 J MATERN-FETAL NEO M
JI J. Matern.-Fetal Neonatal Med.
PD NOV
PY 2013
VL 26
IS 16
BP 1590
EP 1594
DI 10.3109/14767058.2013.795534
PG 5
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 238YP
UT WOS:000325988600006
PM 23650977
ER
PT J
AU Harford, TC
Chen, CM
Saha, TD
Smith, SM
Ruan, WJ
Grant, BE
AF Harford, Thomas C.
Chen, Chiung M.
Saha, Tulshi D.
Smith, Sharon M.
Ruan, W. June
Grant, Bridget E.
TI DSM-IV personality disorders and associations with externalizing and
internalizing disorders: Results from the National Epidemiologic Survey
on Alcohol and Related Conditions
SO JOURNAL OF PSYCHIATRIC RESEARCH
LA English
DT Article
DE DSM-IV personality disorders; DSM-IV substance use disorders; DSM-IV
mood and anxiety disorders; Epidemiology; Structural equation modeling
ID COMMON MENTAL-DISORDERS; GENERAL-POPULATION SAMPLE; PSYCHIATRIC
DIAGNOSTIC MODULES; INTERVIEW SCHEDULE AUDADIS; ENVIRONMENTAL
RISK-FACTORS; SUBSTANCE USE DISORDERS; UNITED-STATES; III-R;
HIERARCHICAL STRUCTURE; ANXIETY DISORDERS
AB Background: Although associations between personality disorders and psychiatric disorders are well established in general population studies, their association with liability dimensions for externalizing and internalizing disorders has not been fully assessed. The purpose of this study is to examine associations between personality disorders (PDs) and lifetime externalizing and internalizing Axis I disorders.
Methods: Data were obtained from the total sample of 34,653 respondents from Wave 2 of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC). Drawing on the literature, a 3-factor exploratory structural equation model was selected to simultaneously assess the measurement relations among DSM-IV Axis I substance use and mood and anxiety disorders and the structural relations between the latent internalizing externalizing dimensions and DSM-IV PDs, adjusting for gender, age, race/ethnicity, and marital status.
Results: Antisocial, histrionic, and borderline PDs were strong predictors for the externalizing factor, while schizotypal, borderline, avoidant, and obsessive-compulsive PDs had significantly larger effects on the internalizing fear factor when compared to the internalizing misery factor. Paranoid, schizoid, narcissistic, and dependent PDs provided limited discrimination between and among the three factors. An overarching latent factor representing general personality dysfunction was significantly greater on the internalizing fear factor followed by the externalizing factor, and weakest for the internalizing misery factor.
Conclusion: Personality disorders offer important opportunities for studies on the externalizing internalizing spectrum of common psychiatric disorders. Future studies based on panic, anxiety, and depressive symptoms may elucidate PD associations with the internalizing spectrum of disorders. Published by Elsevier Ltd.
C1 [Harford, Thomas C.; Chen, Chiung M.] CSR Inc, Arlington, VA 22201 USA.
[Saha, Tulshi D.; Smith, Sharon M.; Ruan, W. June; Grant, Bridget E.] NIAAA, NIH, Bethesda, MD 20892 USA.
RP Chen, CM (reprint author), CSR Inc, 2107 Wilson Blvd,Suite 1000, Arlington, VA 22201 USA.
EM cchen@csrincorporated.com
FU National Institute on Alcohol Abuse and Alcoholism (NIAAA), National
Institutes of Health (NIH); NIAAA [HHSN267200800023C]
FX This research was supported in part by the Intramural Research Program
of the National Institute on Alcohol Abuse and Alcoholism (NIAAA),
National Institutes of Health (NIH), and by the Alcohol Epidemiologic
Data System funded by NIAAA Contract No. HHSN267200800023C to CSR,
Incorporated.
NR 57
TC 5
Z9 5
U1 2
U2 25
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0022-3956
EI 1879-1379
J9 J PSYCHIATR RES
JI J. Psychiatr. Res.
PD NOV
PY 2013
VL 47
IS 11
BP 1708
EP 1716
DI 10.1016/j.jpsychires.2013.07.016
PG 9
WC Psychiatry
SC Psychiatry
GA 237AW
UT WOS:000325841600022
PM 23932575
ER
PT J
AU Hill, ER
Koganti, S
Zhi, J
Megyola, C
Freeman, AF
Palendira, U
Tangye, SG
Farrell, PJ
Bhaduri-McIntosha, S
AF Hill, Erik R.
Koganti, Siva
Zhi, Jizu
Megyola, Cynthia
Freeman, Alexandra F.
Palendira, Umaimainthan
Tangye, Stuart G.
Farrell, Paul J.
Bhaduri-McIntosha, Sumita
TI Signal Transducer and Activator of Transcription 3 Limits Epstein-Barr
Virus Lytic Activation in B Lymphocytes
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID HYPER-IGE SYNDROME; LYMPHOPROLIFERATIVE DISEASE;
INFECTIOUS-MONONUCLEOSIS; GENE-EXPRESSION; STAT3; CELLS; CYCLE;
REPLICATION; MUTATIONS; CANCER
AB Lytic activation of Epstein-Barr virus (EBV) is central to its life cycle and to most EBV-related diseases. However, not every EBV-infected B cell is susceptible to lytic activation. This lack of uniform susceptibility to lytic activation also directly impacts the success of viral oncolytic therapy for EBV cancers, yet determinants of susceptibility to lytic induction signals are not well understood. To determine if host factors influence susceptibility to EBV lytic activation, we developed a technique to separate lytic from refractory cells and reported that EBV lytic activation occurs preferentially in cells with lower levels of signal transducer and activator of transcription 3 (STAT3). Using this tool to detect single cells, we now extend the correlation between STAT3 and lytic versus refractory states to EBV-infected circulating B cells in patients with primary EBV infection, leading us to investigate whether STAT3 controls susceptibility to EBV lytic activation. In loss-of-function and gain-of-function studies in EBV-positive B lymphoma and lymphoblastoid cells, we found that the levels of functional STAT3 regulate susceptibility to EBV lytic activation. This prompted us to identify a pool of candidate cellular genes that might be regulated by STAT3 to limit EBV lytic activation. From this pool, we confirmed increases in transcript levels in refractory cells of a set of genes known to participate in transcription repression. Taken together, our findings place STAT3 at a critical crossroads between EBV latency and lytic activation, processes fundamental to EBV lymphomagenesis.
C1 [Hill, Erik R.; Koganti, Siva; Bhaduri-McIntosha, Sumita] SUNY Stony Brook, Dept Pediat, Div Infect Dis, Stony Brook, NY 11794 USA.
[Hill, Erik R.; Koganti, Siva; Bhaduri-McIntosha, Sumita] SUNY Stony Brook, Stony Brook Childrens Hosp, Stony Brook, NY 11794 USA.
[Zhi, Jizu] SUNY Stony Brook, Sch Med, Bioinformat Core Facil, Stony Brook, NY 11794 USA.
[Megyola, Cynthia] Yale Univ, Sch Med, Dept Genet, New Haven, CT 06510 USA.
[Freeman, Alexandra F.] NIH, Lab Clin Infect Dis, Immunopathogenesis Sect, Bethesda, MD 20892 USA.
[Palendira, Umaimainthan; Tangye, Stuart G.] Garvan Inst Med Res, Program Immunol, Darlinghurst, NSW, Australia.
[Palendira, Umaimainthan; Tangye, Stuart G.] Univ NSW, St Vincents Clin Sch, Sydney, NSW, Australia.
[Farrell, Paul J.] Imperial Coll, Fac Med, Virol Sect, London, England.
[Bhaduri-McIntosha, Sumita] SUNY Stony Brook, Dept Mol Genet & Microbiol, Stony Brook, NY 11794 USA.
RP Hill, ER (reprint author), Campbell Univ Coll Pharm & Hlth Sci, Dept Publ Hlth, Buies Creek, NC USA.
EM sumita.bhaduri-mcintosh@stonybrookmedicine.edu
RI Tangye, Stuart/H-4023-2014;
OI Farrell, Paul/0000-0002-6754-9351
FU National Health and Medical Research Council of Australia; New South
Wales Cancer Council; Research Foundation for The State University of
New York; [K08 AI062732]; [K12 HD001401]; [1UL1RR024139-02]
FX This study was supported by grants K08 AI062732, K12 HD001401, and
1UL1RR024139-02 and funds from The Research Foundation for The State
University of New York to S. B.-M and from the National Health and
Medical Research Council of Australia and the New South Wales Cancer
Council to S.G.T.
NR 44
TC 14
Z9 16
U1 1
U2 9
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 2013
VL 87
IS 21
BP 11438
EP 11446
DI 10.1128/JVI.01762-13
PG 9
WC Virology
SC Virology
GA 237IR
UT WOS:000325863400011
PM 23966384
ER
PT J
AU Welbourn, S
Dutta, SM
Semmes, OJ
Strebel, K
AF Welbourn, Sarah
Dutta, Sucharita M.
Semmes, O. John
Strebel, Klaus
TI Restriction of Virus Infection but Not Catalytic dNTPase Activity Is
Regulated by Phosphorylation of SAMHD1
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID AICARDI-GOUTIERES SYNDROME; CYCLIN-DEPENDENT KINASES; HUMAN DENDRITIC
CELLS; CD4(+) T-CELLS; HIV-1 RESTRICTION; DEOXYNUCLEOSIDE TRIPHOSPHATES;
PROTEIN; VPX; IDENTIFICATION; MACROPHAGES
AB SAMHD1 is a host protein responsible, at least in part, for the inefficient infection of dendritic, myeloid, and resting T cells by HIV-1. Interestingly, HIV-2 and SIVsm viruses are able to counteract SAMHD1 by targeting it for proteasomal degradation using their Vpx proteins. It has been proposed that SAMHD1 is a dGTP-dependent deoxynucleoside triphosphohydrolase (dNT-Pase) that restricts HIV-1 by reducing cellular dNTP levels to below that required for reverse transcription. However, nothing is known about SAMHD1 posttranslational modifications and their potential role in regulating SAMHD1 function. We used P-32 labeling and immunoblotting with phospho-specific antibodies to identify SAMHD1 as a phosphoprotein. Several amino acids in SAMHD1 were identified to be sites of phosphorylation using direct mass spectrometry. Mutation of these residues to alanine to prevent phosphorylation or to glutamic acid to mimic phosphorylation had no effect on the nuclear localization of SAMHD1 or its sensitivity to Vpx-mediated degradation. Furthermore, neither alanine nor glutamic acid substitutions had a significant effect on SAMHD1 dNTPase activity in an in vitro assay. Interestingly, however, we found that a T592E mutation, mimicking constitutive phosphorylation at a main phosphorylation site, severely affected the ability of SAMHD1 to restrict HIV-1 in a U937 cell-based restriction assay. In contrast, a T592A mutant was still capable of restricting HIV-1. These results indicate that SAMHD1 phosphorylation may be a negative regulator of SAMHD1 restriction activity. This conclusion is supported by our finding that SAMHD1 is hyperphosphorylated in monocytoid THP-1 cells under nonrestrictive conditions.
C1 [Welbourn, Sarah; Strebel, Klaus] NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA.
[Dutta, Sucharita M.; Semmes, O. John] Eastern Virginia Med Sch, Leroy T Canoles Jr Canc Res Ctr, Norfolk, VA 23501 USA.
RP Strebel, K (reprint author), NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA.
EM kstrebel@nih.gov
FU National Institutes of Health (NIH), National Institute of Allergy and
Infectious Diseases; Canadian Institutes of Health Research (C.I.H.R);
NIH [CA76959]
FX This study was supported in part by the Intramural Research Program of
the National Institutes of Health (NIH), National Institute of Allergy
and Infectious Diseases, to K.S. and by NIH grant CA76959 to O.J.S. We
acknowledge the contribution of the George L. Wright Center for
Biomedical Proteomics. S.W. was supported by a postdoctoral fellowship
from the Canadian Institutes of Health Research (C.I.H.R).
NR 36
TC 57
Z9 57
U1 0
U2 4
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
EI 1098-5514
J9 J VIROL
JI J. Virol.
PD NOV
PY 2013
VL 87
IS 21
BP 11516
EP 11524
DI 10.1128/JVI.01642-13
PG 9
WC Virology
SC Virology
GA 237IR
UT WOS:000325863400018
PM 23966382
ER
PT J
AU Delviks-Frankenberry, K
Paprotka, T
Cingoz, O
Wildt, S
Hu, WS
Coffin, JM
Pathak, VK
AF Delviks-Frankenberry, Krista
Paprotka, Tobias
Cingoez, Oya
Wildt, Sheryl
Hu, Wei-Shau
Coffin, John M.
Pathak, Vinay K.
TI Generation of Multiple Replication-Competent Retroviruses through
Recombination between PreXMRV-1 and PreXMRV-2
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID MURINE LEUKEMIA-VIRUS; CHRONIC-FATIGUE-SYNDROME; NUDE-MICE; INFECTIOUS
RETROVIRUS; CELL-LINES; NIH SWISS; XMRV; CANCER; PCR; TUMORS
AB We previously identified two novel endogenous murine leukemia virus proviruses, PreXMRV-1 and PreXMRV-2, and showed that they most likely recombined during xenograft passaging of a human prostate tumor in mice to generate xenotropic murine leukemia virus-related virus (XMRV). To determine the recombination potential of PreXMRV-1 and PreXMRV-2, we examined the generation of replication-competent retroviruses (RCRs) over time in a cell culture system. We observed that either virus alone was noninfectious and the RNA transcripts of the viruses were undetectable in the blood and spleen of nude mice that carry them. To determine their potential to generate RCRs through recombination, we transfected PreXMRV-1 and PreXMRV-2 into 293T cells and used the virus produced to infect fresh cells; the presence of reverse transcriptase activity at 10 days postinfection indicated the presence of RCRs. Population sequencing of proviral DNA indicated that all RCRs contained the gag and 5' half of pol from PreXMRV-2 and the long terminal repeat, 3' half of pol (including integrase), and env from PreXMRV-1. All crossovers were within sequences of at least 9 identical nucleotides, and crossovers within each of two selected recombination zones of 415 nucleotides (nt) in the 5' untranslated region and 982 nt in pol were required to generate RCRs. A recombinant with the same genotype as XMRV was not detected, and our analysis indicates that the probability of generating an identical RCR is vanishingly small. In addition, the studies indicate that the process of RCR formation is primarily driven by selection for viable cis and trans elements from the parental proviruses.
C1 [Delviks-Frankenberry, Krista; Paprotka, Tobias; Pathak, Vinay K.] NCI, Viral Mutat Sect, HIV Drug Resistance Program, Frederick, MD 21701 USA.
[Hu, Wei-Shau] NCI, Viral Recombinat Sect, HIV Drug Resistance Program, Frederick, MD 21701 USA.
[Cingoez, Oya; Coffin, John M.] Tufts Univ, Genet Program, Sackler Sch Grad Biomed Sci, Boston, MA 02111 USA.
[Wildt, Sheryl] Harlan Labs, Indianapolis, IN USA.
RP Pathak, VK (reprint author), NCI, Viral Mutat Sect, HIV Drug Resistance Program, Frederick, MD 21701 USA.
EM vinay.pathak@nih.gov
RI Delviks-Frankenberry, Krista/M-4822-2013
FU Bench-to-Bedside Award from the National Cancer Institute [R37 CA
089441]; F. M. Kirby Foundation
FX This work was supported in part by a Bench-to-Bedside Award to V.K.P.
and grant R37 CA 089441 to J.M.C. from the National Cancer Institute.
J.M.C. was a research professor of the American Cancer Society with
support from the F. M. Kirby Foundation.
NR 51
TC 5
Z9 5
U1 0
U2 7
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
EI 1098-5514
J9 J VIROL
JI J. Virol.
PD NOV
PY 2013
VL 87
IS 21
BP 11525
EP 11537
DI 10.1128/JVI.01787-13
PG 13
WC Virology
SC Virology
GA 237IR
UT WOS:000325863400019
PM 23966380
ER
PT J
AU Choi, YP
Priola, SA
AF Choi, Young Pyo
Priola, Suzette A.
TI A Specific Population of Abnormal Prion Protein Aggregates Is
Preferentially Taken Up by Cells and Disaggregated in a Strain-Dependent
Manner
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES; CREUTZFELDT-JAKOB-DISEASE;
IN-VITRO; DENDRITIC CELLS; CULTURED-CELLS; NEURONAL CELLS;
POLYSACCHARIDE SCAFFOLD; SCRAPIE INFECTION; PRP ACCUMULATION;
NUCLEIC-ACIDS
AB Prion diseases are characterized by the conversion of the soluble protease-sensitive host-encoded prion protein (PrPC) into its aggregated, protease-resistant, and infectious isoform (PrPSc). One of the earliest events occurring in cells following exposure to an exogenous source of prions is the cellular uptake of PrPSc. It is unclear how the biochemical properties of PrPSc influence its uptake, although aggregate size is thought to be important. Here we show that for two different strains of mouse prions, one that infects cells (22L) and one that does not (87V), a fraction of PrPSc associated with distinct sedimentation properties is preferentially taken up by the cells. However, while the fraction of PrPSc and the kinetics of uptake were similar for both strains, PrPSc derived from the 87V strain was disaggregated more rapidly than that derived from 22L. The increased rate of PrPSc disaggregation did not correlate with either the conformational or aggregate stability of 87V PrPSc, both of which were greater than those of 22L PrPSc. Our data suggest that the kinetics of disaggregation of PrPSc following cellular uptake is independent of PrPSc stability but may be dependent upon some component of the PrPSc aggregate other than PrP. Rapid disaggregation of 87V PrPSc by the cell may contribute, at least in part, to the inability of 87V to infect cells in vitro.
C1 [Choi, Young Pyo; Priola, Suzette A.] NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA.
RP Priola, SA (reprint author), NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA.
EM spriola@niaid.nih.gov
FU 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 55
TC 3
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 2013
VL 87
IS 21
BP 11552
EP 11561
DI 10.1128/JVI.01484-13
PG 10
WC Virology
SC Virology
GA 237IR
UT WOS:000325863400021
PM 23966386
ER
PT J
AU Hatch, SC
Sardo, L
Chen, JB
Burdick, R
Gorelick, R
Fivash, MJ
Pathak, VK
Hu, WS
AF Hatch, Steven C.
Sardo, Luca
Chen, Jianbo
Burdick, Ryan
Gorelick, Robert
Fivash, Matthew J., Jr.
Pathak, Vinay K.
Hu, Wei-Shau
TI Gag-Dependent Enrichment of HIV-1 RNA near the Uropod Membrane of
Polarized T Cells
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID VIROLOGICAL SYNAPSES; BINDING PROTEIN; LOCALIZATION; TRANSLATION;
LYMPHOCYTE; MOTILITY; SPREAD; DOMAIN
AB The enrichment of HIV-1 macromolecules at the uropod of polarized T cells can significantly promote virus assembly and cell-mediated infection. Using live-cell fluorescence microscopy, we demonstrate that full-length HIV-1 RNA is enriched at the uropod membrane; furthermore, the presence of HIV-1 Gag containing a functional nucleocapsid domain is necessary for this HIV-1 RNA enrichment. The results from these studies provide novel insights into the mechanism of HIV-1 replication in polarized T cells.
C1 [Hatch, Steven C.; Sardo, Luca; Chen, Jianbo; Hu, Wei-Shau] NCI, Viral Recombinat Sect, HIV Drug Resistance Program, Frederick, MD 21701 USA.
[Burdick, Ryan; Pathak, Vinay K.] NCI, Viral Mutat Sect, HIV Drug Resistance Program, Frederick, MD 21701 USA.
[Gorelick, Robert] Frederick Natl Lab Canc Res, AIDS & Canc Virus Program, SAIC Frederick, Frederick, MD USA.
[Fivash, Matthew J., Jr.] Data Management Serv Inc, Frederick, MD USA.
RP Hu, WS (reprint author), NCI, Viral Recombinat Sect, HIV Drug Resistance Program, Frederick, MD 21701 USA.
EM Wei-Shau.Hu@nih.gov
RI Chen, Jianbo/N-3737-2014
OI Chen, Jianbo/0000-0001-6491-6577
FU Intramural AIDS Targeted Antiviral Program, NIH; Intramural Research
Program of the Center for Cancer Research, NCI; NCI, NIH
[HHSN261200800001E]; SAIC-Frederick, Inc.
FX This work was funded in part by the Intramural AIDS Targeted Antiviral
Program, NIH, and the Intramural Research Program of the Center for
Cancer Research, NCI, and in part with federal funds from the NCI, NIH,
under contract no. HHSN261200800001E with SAIC-Frederick, Inc.
NR 26
TC 2
Z9 2
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 2013
VL 87
IS 21
BP 11912
EP 11915
DI 10.1128/JVI.01680-13
PG 4
WC Virology
SC Virology
GA 237IR
UT WOS:000325863400053
PM 23966405
ER
PT J
AU Gao, F
Gulay, SP
Kasprzak, W
Dinman, JD
Shapiro, BA
Simon, AE
AF Gao, Feng
Gulay, Suna P.
Kasprzak, Wojciech
Dinman, Jonathan D.
Shapiro, Bruce A.
Simon, Anne E.
TI The Kissing-Loop T-Shaped Structure Translational Enhancer of Pea
Enation Mosaic Virus Can Bind Simultaneously to Ribosomes and a 5 '
Proximal Hairpin
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID CAP-INDEPENDENT TRANSLATION; TURNIP CRINKLE VIRUS; PLANT VIRAL RNAS;
MESSENGER-RNA; INITIATION-FACTOR; STEM-LOOP; 3' UTR; ELEMENT;
REPLICATION; PROTEIN
AB The Pea enation mosaic virus (PEMV) 3 ' translational enhancer, known as the kissing-loop T-shaped structure (kl-TSS), binds to 40S subunits, 60S subunits, and 80S ribosomes, whereas the Turnip crinkle virus (TCV) TSS binds only to 60S subunits and 80S ribosomes. Using electrophoretic mobility gel shift assay (EMSA)-based competition assays, the kl-TSS was found to occupy a different site in the ribosome than the P-site-binding TCV TSS, suggesting that these two TSS employ different mechanisms for enhancing translation. The kl-TSS also engages in a stable, long-distance RNA-RNA kissing-loop interaction with a 12-bp 5 ' coding-region hairpin that does not alter the structure of the kl-TSS as revealed by molecular dynamics simulations. Addition of the kl-TSS in trans to a luciferase reporter construct containing either wild-type or mutant 5 ' and 3 ' PEMV sequences suppressed translation, suggesting that the kl-TSS is required in cis to function, and both ribosome-binding and RNA interaction activities of the kl-TSS contributed to translational inhibition. Addition of the kl-TSS was more detrimental for translation than an adjacent eIF4E-binding 3 ' translational enhancer known as the PTE, suggesting that the PTE may support the ribosome-binding function of the kl-TSS. Results of in-line RNA structure probing, ribosome filter binding, and high-throughput selective 2 '-hydroxyl acylation analyzed by primer extension (hSHAPE) of rRNAs within bound ribosomes suggest that kl-TSS binding to ribosomes and binding to the 5 ' hairpin are compatible activities. These results suggest a model whereby posttermination ribosomes/ribosomal subunits bind to the kl-TSS and are delivered to the 5 ' end of the genome via the associated RNA-RNA interaction, which enhances the rate of translation reinitiation.
C1 [Gao, Feng; Gulay, Suna P.; Dinman, Jonathan D.; Simon, Anne E.] Univ Maryland, Dept Cell Biol & Mol Genet, College Pk, MD 20742 USA.
[Kasprzak, Wojciech] SAIC Frederick Inc, Basic Sci Program, Ctr Canc Res Nanobiol Program, Frederick Natl Lab Canc Res, Frederick, MD USA.
[Shapiro, Bruce A.] NCI, Ctr Canc Res Nanobiol Program, Frederick, MD 21701 USA.
RP Shapiro, BA (reprint author), NCI, Ctr Canc Res Nanobiol Program, Frederick, MD 21701 USA.
EM shapirbr@mail.nih.gov; simona@umd.edu
RI Gao, Feng/K-4403-2015;
OI Dinman, Jonathan/0000-0002-2402-9698
FU U.S. Public Health Service [GM 061515-05A2/G120CD, GM 061515-07S1, GM
058859]; NSF [MCB 1157906]; Frederick National Laboratory for Cancer
Research, National Institutes of Health [HHSN 261200800001]; Intramural
Research Program of the National Institutes of Health, Center for Cancer
Research
FX This work was supported by grants from the U.S. Public Health Service
(GM 061515-05A2/G120CD and GM 061515-07S1) and the NSF (MCB 1157906) to
A. E. S. and from the U.S. Public Health Service (GM 058859) to J.D.D.
This publication was also funded in part by federal funds from the
Frederick National Laboratory for Cancer Research, National Institutes
of Health, under contract HHSN 261200800001E to W.K. This research was
additionally supported in part by a grant from the Intramural Research
Program of the National Institutes of Health, Center for Cancer
Research, to B.A.S.
NR 57
TC 9
Z9 9
U1 0
U2 11
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 2013
VL 87
IS 22
BP 11987
EP 12002
DI 10.1128/JVI.02005-13
PG 16
WC Virology
SC Virology
GA 237JJ
UT WOS:000325865400003
PM 23986599
ER
PT J
AU Kerr, PJ
Rogers, MB
Fitch, A
DePasse, JV
Cattadori, IM
Hudson, PJ
Tscharke, DC
Holmes, EC
Ghedin, E
AF Kerr, Peter J.
Rogers, Matthew B.
Fitch, Adam
DePasse, Jay V.
Cattadori, Isabella M.
Hudson, Peter J.
Tscharke, David C.
Holmes, Edward C.
Ghedin, Elodie
TI Comparative Analysis of the Complete Genome Sequence of the California
MSW Strain of Myxoma Virus Reveals Potential Host Adaptations
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID RABBIT FIBROMA VIRUS; TUMORIGENIC POXVIRUSES; MAXIMUM-LIKELIHOOD;
VIRULENCE; RECOMBINATION; REPLICATION; SUPEROXIDE; DISMUTASE; HOMOLOGS;
CELLS
AB Myxomatosis is a rapidly lethal disease of European rabbits that is caused by myxoma virus (MYXV). The introduction of a South American strain of MYXV into the European rabbit population of Australia is the classic case of host-pathogen coevolution following cross-species transmission. The most virulent strains of MYXV for European rabbits are the Californian viruses, found in the Pacific states of the United States and the Baja Peninsula, Mexico. The natural host of Californian MYXV is the brush rabbit, Sylvilagus bachmani. We determined the complete sequence of the MSW strain of Californian MYXV and performed a comparative analysis with other MYXV genomes. The MSW genome is larger than that of the South American Lausanne (type) strain of MYXV due to an expansion of the terminal inverted repeats (TIRs) of the genome, with duplication of the M156R, M154L, M153R, M152R, and M151R genes and part of the M150R gene from the right-hand (RH) end of the genome at the left-hand (LH) TIR. Despite the extreme virulence of MSW, no novel genes were identified; five genes were disrupted by multiple indels or mutations to the ATG start codon, including two genes, M008.1L/R and M152R, with major virulence functions in European rabbits, and a sixth gene, M000.5L/R, was absent. The loss of these gene functions suggests that S. bachmani is a relatively recent host for MYXV and that duplication of virulence genes in the TIRs, gene loss, or sequence variation in other genes can compensate for the loss of M008.1L/R and M152R in infections of European rabbits.
C1 [Kerr, Peter J.] CSIRO Ecosyst Sci, Canberra, ACT, Australia.
[Rogers, Matthew B.; Ghedin, Elodie] Univ Pittsburgh, Sch Med, Dept Computat & Syst Biol, Pittsburgh, PA 15260 USA.
[Rogers, Matthew B.; Fitch, Adam; DePasse, Jay V.; Ghedin, Elodie] Univ Pittsburgh, Sch Med, Ctr Vaccine Res, Pittsburgh, PA USA.
[Cattadori, Isabella M.; Hudson, Peter J.] Penn State Univ, Dept Biol, Ctr Infect Dis Dynam, University Pk, PA 16802 USA.
[Tscharke, David C.] Australian Natl Univ, Res Sch Biol, Canberra, ACT, Australia.
[Holmes, Edward C.] Univ Sydney, Sch Biol Sci, Sydney Emerging Infect & Biosecur Inst, Sydney, NSW 2006, Australia.
[Holmes, Edward C.] Univ Sydney, Sydney Med Sch, Sydney, NSW 2006, Australia.
[Holmes, Edward C.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Ghedin, E (reprint author), Univ Pittsburgh, Sch Med, Dept Computat & Syst Biol, Pittsburgh, PA 15260 USA.
EM elg21@pitt.edu
RI Tscharke, David/C-9133-2009;
OI Tscharke, David/0000-0001-6825-9172; Holmes, Edward/0000-0001-9596-3552
FU National Institute of Allergy and Infectious Diseases, National
Institutes of Health [R01 AI093804]; NHMRC Australia Fellowship; ARC
Future Fellowship
FX This work was funded in part by grant R01 AI093804 from the National
Institute of Allergy and Infectious Diseases, National Institutes of
Health. E.C.H. was supported by an NHMRC Australia Fellowship, and
D.C.T. was supported by an ARC Future Fellowship.
NR 45
TC 9
Z9 9
U1 1
U2 8
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
EI 1098-5514
J9 J VIROL
JI J. Virol.
PD NOV
PY 2013
VL 87
IS 22
BP 12080
EP 12089
DI 10.1128/JVI.01923-13
PG 10
WC Virology
SC Virology
GA 237JJ
UT WOS:000325865400010
PM 23986601
ER
PT J
AU Han, SJ
Marshall, V
Barsov, E
Quinones, O
Ray, A
Labo, N
Trivett, M
Ott, D
Renne, R
Whitby, D
AF Han, Soo-Jin
Marshall, Vickie
Barsov, Eugene
Quinones, Octavio
Ray, Alex
Labo, Nazzarena
Trivett, Matthew
Ott, David
Renne, Rolf
Whitby, Denise
TI Kaposi's Sarcoma-Associated Herpesvirus MicroRNA SingleNucleotide
Polymorphisms Identified in Clinical Samples Can Affect MicroRNA
Processing, Level of Expression, and Silencing Activity
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID MULTICENTRIC CASTLEMAN-DISEASE; PRIMARY EFFUSION LYMPHOMA; LYTIC SWITCH
PROTEIN; DNA-SEQUENCES; CELL-LINES; IN-VITRO; DROSHA; BIOGENESIS;
TRANSCRIPTION; RECOGNITION
AB Kaposi's sarcoma-associated herpesvirus (KSHV) encodes 12 pre-microRNAs that can produce 25 KSHV mature microRNAs. We previously reported single-nucleotide polymorphisms (SNPs) in KSHV-encoded pre-microRNA and mature microRNA sequences from clinical samples (V. Marshall et al., J. Infect. Dis., 195:645-659, 2007). To determine whether microRNA SNPs affect pre-microRNA processing and, ultimately, mature microRNA expression levels, we performed a detailed comparative analysis of (i) mature microRNA expression levels, (ii) in vitro Drosha/Dicer processing, and (iii) RNA-induced silencing complex-dependent targeting of wild-type (wt) and variant microRNA genes. Expression of pairs of wt and variant pre-microRNAs from retroviral vectors and measurement of KSHV mature microRNA expression by real-time reverse transcription-PCR (RT-PCR) revealed differential expression levels that correlated with the presence of specific sequence polymorphisms. Measurement of KSHV mature microRNA expression in a panel of primary effusion lymphoma cell lines by real-time RT-PCR recapitulated some observed expression differences but suggested a more complex relationship between sequence differences and expression of mature microRNA. Furthermore, in vitro maturation assays demonstrated significant SNP-associated changes in Drosha/DGCR8 and/or Dicer processing. These data demonstrate that SNPs within KSHV-encoded pre-microRNAs are associated with differential microRNA expression levels. Given the multiple reports on the involvement of microRNAs in cancer, the biological significance of these phenotypic and genotypic variants merits further studies in patients with KSHV-associated malignancies.
C1 [Han, Soo-Jin; Renne, Rolf] Univ Florida, Dept Mol Genet & Microbiol, Gainesville, FL USA.
[Marshall, Vickie; Barsov, Eugene; Ray, Alex; Labo, Nazzarena; Trivett, Matthew; Ott, David; Whitby, Denise] SAIC Frederick, AIDS & Canc Virus Program, Frederick Natl Lab Canc Res, Frederick, MD USA.
[Quinones, Octavio] Frederick Natl Lab Canc Res, Comp Serv, Frederick, MD USA.
[Quinones, Octavio] Frederick Natl Lab Canc Res, Stat Serv, Frederick, MD USA.
RP Whitby, D (reprint author), SAIC Frederick, AIDS & Canc Virus Program, Frederick Natl Lab Canc Res, Frederick, MD USA.
EM whitbyd@mail.nih.gov
RI Labo, Nazzarena/H-8655-2012
OI Labo, Nazzarena/0000-0001-5953-4064
FU National Cancer Institute, National Institutes of Health
[HHSN261200800001E]; [RO1 119917-6]
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 and by RO1 119917-6 to R.R.
NR 43
TC 10
Z9 10
U1 0
U2 4
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
EI 1098-5514
J9 J VIROL
JI J. Virol.
PD NOV
PY 2013
VL 87
IS 22
BP 12237
EP 12248
DI 10.1128/JVI.01202-13
PG 12
WC Virology
SC Virology
GA 237JJ
UT WOS:000325865400025
PM 24006441
ER
PT J
AU Maruri-Avidal, L
Weisberg, AS
Moss, B
AF Maruri-Avidal, Liliana
Weisberg, Andrea S.
Moss, Bernard
TI Direct Formation of Vaccinia Virus Membranes from the Endoplasmic
Reticulum in the Absence of the Newly Characterized L2-Interacting
Protein A30.5
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID GOLGI INTERMEDIATE COMPARTMENT; A17L ENVELOPE PROTEIN; VIRION MEMBRANE;
IMMATURE VIRIONS; VIRAL MEMBRANES; CRESCENT PRECURSORS; APOPTOTIC
MIMICRY; EXTERNAL SCAFFOLD; MATURE VIRIONS; CELL ENTRY
AB Crescents consisting of a single lipoprotein membrane with an external protein scaffold comprise the initial structural elements of poxvirus morphogenesis. Crescents enlarge to form spherical immature virions, which enclose viroplasm consisting of proteins destined to form the cores of mature virions. Previous studies suggest that the L2 protein participates in the recruitment of endoplasmic reticulum (ER)-derived membranes to form immature virions within assembly sites of cytoplasmic factories. Here we show that L2 interacts with the previously uncharacterized 42-amino-acid A30.5 protein. An open reading frame similar in size to the one encoding A30.5 is at the same genome location in representatives of all chordopoxvirus genera. A30.5 has a putative transmembrane domain and colocalized with markers of the endoplasmic reticulum and with L2. By constructing a complementing cell line expressing A30.5, we isolated a deletion mutant virus that exhibits a defect in morphogenesis in normal cells. Large electron-dense cytoplasmic inclusions and clusters of scaffold protein-coated membranes that resemble crescents and immature virions devoid of viroplasm were seen in place of normal structures. Crescent-shaped membranes were continuous with the endoplasmic reticulum membrane and oriented with the convex scaffold protein-coated side facing the lumen, while clusters of completed spherical immature-virion-like forms were trapped within the expanded lumen. Immature-virion-like structures were more abundant in infected RK-13 cells than in BS-C-1 or HeLa cells, in which cytoplasmic inclusions were decorated with scaffold protein-coated membrane arcs. We suggest that the outer surface of the poxvirus virion is derived from the luminal side of the ER membrane.
C1 [Maruri-Avidal, Liliana; Weisberg, Andrea S.; Moss, Bernard] NIAID, Viral Dis Lab, Bethesda, MD 20892 USA.
RP Moss, B (reprint author), NIAID, Viral Dis Lab, Bethesda, MD 20892 USA.
EM bmoss@nih.gov
FU Division of Intramural Research, NIAID, NIH
FX The research was supported by the Division of Intramural Research,
NIAID, NIH.
NR 47
TC 14
Z9 14
U1 0
U2 3
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
EI 1098-5514
J9 J VIROL
JI J. Virol.
PD NOV
PY 2013
VL 87
IS 22
BP 12313
EP 12326
DI 10.1128/JVI.02137-13
PG 14
WC Virology
SC Virology
GA 237JJ
UT WOS:000325865400032
PM 24027302
ER
PT J
AU Tan, Y
Guan, WD
Lam, TTY
Pan, SH
Wu, SG
Zhan, YQ
Viboud, C
Holmes, EC
Yang, ZF
AF Tan, Yi
Guan, Wenda
Lam, Tommy Tsan-Yuk
Pan, Sihua
Wu, Shiguan
Zhan, Yangqing
Viboud, Cecile
Holmes, Edward C.
Yang, Zifeng
TI Differing Epidemiological Dynamics of Influenza B Virus Lineages in
Guangzhou, Southern China, 2009-2010
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID EVOLUTIONARY PATTERN; MAXIMUM-LIKELIHOOD; GENETIC-CHARACTERIZATION;
CLINICAL CHARACTERISTICS; SEASONAL INFLUENZA; A VIRUSES; COCIRCULATION;
STRAINS; TAIWAN; HEMAGGLUTININS
AB The epidemiological and evolutionary dynamics of the two cocirculating lineages of influenza B virus, Victoria and Yamagata, are poorly understood, especially in tropical or subtropical areas of Southeast Asia. We performed a phylogenetic analysis of the hemagglutinin (HA) and neuraminidase (NA) sequences of influenza B viruses isolated in Guangzhou, a southern Chinese city, during 2009 to 2010 and compared the demographic and clinical features of infected patients. We identified multiple viral introductions of Victoria strains from both Chinese and international sources, which formed two phylogenetically and antigenically distinct clades (Victoria 1 and 2), some of which persisted between seasons. We identified one dominant Yamagata introduction from outside China during 2009. Our phylogenetic analysis reveals the occurrence of reassortment events among the Victoria and Yamagata lineages and also within the Victoria lineage. We found no significant difference in clinical severity by influenza B lineage, with the exceptions that (i) the Yamagata lineage infected older people than either Victoria lineage and (ii) fewer upper respiratory tract infections were caused by the Victoria 2 than the Victoria 1 clade. Overall, our study reveals the complex epidemiological dynamics of different influenza B lineages within a single geographic locality and has implications for vaccination policy in southern China.
C1 [Tan, Yi; Viboud, Cecile; Holmes, Edward C.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Tan, Yi] Chinese Univ Hong Kong, Fac Med, Sch Publ Hlth & Primary Care, Stanley Ho Ctr Emerging Infect Dis, Hong Kong, Hong Kong, Peoples R China.
[Guan, Wenda; Pan, Sihua; Wu, Shiguan; Zhan, Yangqing; Yang, Zifeng] Guangzhou Med Univ, Affiliated Hosp 1, State Key Lab Resp Dis, Guangzhou, Guangdong, Peoples R China.
[Lam, Tommy Tsan-Yuk] Univ Hong Kong, Sch Publ Hlth, Hong Kong, Hong Kong, Peoples R China.
[Holmes, Edward C.] Univ Sydney, Sch Biol Sci, Sydney Emerging Infect & Biosecur Inst, Sydney, NSW 2006, Australia.
[Holmes, Edward C.] Univ Sydney, Sydney Med Sch, Sydney, NSW 2006, Australia.
[Yang, Zifeng] Macau Univ Sci & Technol, Fac Chinese Med, Macao, Peoples R China.
RP Yang, ZF (reprint author), Guangzhou Med Univ, Affiliated Hosp 1, State Key Lab Resp Dis, Guangzhou, Guangdong, Peoples R China.
EM jeffyah@163.com
RI Lam, Tommy Tsan-Yuk/D-4837-2012;
OI Holmes, Edward/0000-0001-9596-3552
FU Combination Project of Guangdong Province from Guangdong Provincial
Department of Science and Technology, China [2010B091000018]; National
Science and Technology Pillar Program during the 12th Five-year Plan
Period from Ministry of Science and Technology, China [2012BAI05B01];
Science Research Fund for Youth Scholar from First Affiliated Hospital
of Guangzhou Medical School, China [201220-gyfyy]; Influenza Program of
the Fogarty International Center, National Institutes of Health; Office
of Global Affairs' International Influenza Unit, U.S. Department of
Health and Human Services; NHMRC Australia
FX This work was supported by a Combination Project of Guangdong Province
from Guangdong Provincial Department of Science and Technology, China
(grant no. 2010B091000018), The National Science and Technology Pillar
Program during the 12th Five-year Plan Period from Ministry of Science
and Technology, China (grant no. 2012BAI05B01), The Science Research
Fund for Youth Scholar from First Affiliated Hospital of Guangzhou
Medical School, China (grant no. 201220-gyfyy), and the Influenza
Program of the Fogarty International Center, National Institutes of
Health, which is funded by the Office of Global Affairs' International
Influenza Unit, U.S. Department of Health and Human Services. E. C. H.
is funded by an NHMRC Australia Fellowship.
NR 53
TC 18
Z9 18
U1 3
U2 9
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 2013
VL 87
IS 22
BP 12447
EP 12456
DI 10.1128/JVI.01039-13
PG 10
WC Virology
SC Virology
GA 237JJ
UT WOS:000325865400044
PM 24027322
ER
PT J
AU Lubaki, NM
Ilinykh, P
Pietzsch, C
Tigabu, B
Freiberg, AN
Koup, RA
Bukreyev, A
AF Lubaki, Ndongala M.
Ilinykh, Philipp
Pietzsch, Colette
Tigabu, Bersabeh
Freiberg, Alexander N.
Koup, Richard A.
Bukreyev, Alexander
TI The Lack of Maturation of Ebola Virus-Infected Dendritic Cells Results
from the Cooperative Effect of at Least Two Viral Domains vol(87, pg
7471, 2013)
SO JOURNAL OF VIROLOGY
LA English
DT Correction
C1 [Lubaki, Ndongala M.] Univ Texas Med Branch, Galveston Natl Lab, Dept Pathol, Galveston, TX 77555 USA.
Univ Texas Med Branch, Galveston Natl Lab, Dept Microbiol & Immunol, Galveston, TX 77555 USA.
NIAID, Immunol Lab, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA.
RP Lubaki, NM (reprint author), Univ Texas Med Branch, Galveston Natl Lab, Dept Pathol, Galveston, TX 77555 USA.
NR 1
TC 0
Z9 0
U1 2
U2 7
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
EI 1098-5514
J9 J VIROL
JI J. Virol.
PD NOV
PY 2013
VL 87
IS 22
BP 12506
EP 12506
DI 10.1128/JVI.02496-13
PG 1
WC Virology
SC Virology
GA 237JJ
UT WOS:000325865400053
ER
PT J
AU Saba, E
Origoni, M
Taccagni, G
Ferrari, D
Doglioni, C
Nava, A
Lisco, A
Grivel, JC
Margolis, L
Poli, G
AF Saba, E.
Origoni, M.
Taccagni, G.
Ferrari, D.
Doglioni, C.
Nava, A.
Lisco, A.
Grivel, J-C
Margolis, L.
Poli, G.
TI Productive HIV-1 infection of human cervical tissue ex vivo is
associated with the secretory phase of the menstrual cycle
SO MUCOSAL IMMUNOLOGY
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; FEMALE REPRODUCTIVE-TRACT; DC-SIGN;
T-CELLS; RHESUS MACAQUES; INNATE IMMUNITY; GENITAL-TRACT; MACROPHAGES;
TRANSMISSION; EXPRESSION
AB Cervical tissue explants (CTEs) from 22 HIV-1 seronegative women were exposed to R5 HIV-1 ex vivo. Eight CTEs were productively infected in terms of HIV-1 p24(Gag) release in culture supernatants, whereas 14 were not. Nonetheless, both accumulation of HIV-1(gag) DNA and of p24(Gag)(+) CD4(+) Tcells and macrophages occurred in both productive and, at lower levels, in nonproductive CTEs. Nonproductive CTEs differed from productive CTEs for higher secretion of C-C motif chemokine ligand 3 (CCL3) and CCL5. A post-hoc analysis revealed that all productive CTEs were established from women in their secretory phase of the menstrual cycle, whereas nonproductive CTEs were derived from women either in their secretory (28%) or proliferative (36%) menstrual cycle phases or with an atrophic endometrium (36%). Thus, our results support the epidemiological observation that sexual HIV-1 transmission from males to women as well as from women to men is more efficient during their secretory phase of the menstrual cycle.
C1 [Saba, E.; Nava, A.; Poli, G.] Ist Sci San Raffaele, Div Immunol Transplantat & Infect Dis, AIDS Immunopathogenesis Unit, I-20132 Milan, Italy.
[Saba, E.; Origoni, M.; Poli, G.] Univ Vita Salute San Raffaele, Sch Med, Milan, Italy.
[Origoni, M.; Ferrari, D.] Ist Sci San Raffaele, Dept Obstet & Gynecol, I-20132 Milan, Italy.
[Taccagni, G.; Doglioni, C.] Ist Sci San Raffaele, Dept Pathol, I-20132 Milan, Italy.
[Lisco, A.; Grivel, J-C; Margolis, L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Phys Biol, NIH, Bethesda, MD USA.
RP Margolis, L (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Phys Biol, NIH, Bethesda, MD USA.
EM margolis@helix.nih.gov; poli.guido@hsr.it
OI ORIGONI, Massimo/0000-0001-6690-3606; DOGLIONI,
Claudio/0000-0002-4969-5216
FU Cariplo Foundation, Milano, Italy; National Program of Research on
HIV/AIDS of the Italian Ministry of Health [AIDS 40H77]; NICHD
FX E. S. conducted this study as student of the Program of Basic and
Applied Immunology, International PhD School in Molecular Medicine, San
Raffaele University, Milan, Italy; E.S.'s PhD fellowship was supported
by a grant of the Cariplo Foundation, Milano, Italy. This study was
supported by the grant AIDS 40H77 of the National Program of Research on
HIV/AIDS of the Italian Ministry of Health (to G. P.). The work of A.
L., J-C.G., and L. M. was supported by the NICHD Intramural Program. We
thank Elisa Vicenzi for helpful discussions.
NR 50
TC 27
Z9 27
U1 0
U2 5
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1933-0219
EI 1935-3456
J9 MUCOSAL IMMUNOL
JI Mucosal Immunol.
PD NOV
PY 2013
VL 6
IS 6
BP 1081
EP 1090
DI 10.1038/mi.2013.2
PG 10
WC Immunology
SC Immunology
GA 238BX
UT WOS:000325916800003
PM 23385427
ER
PT J
AU Cruz, FC
Koya, E
Guez-Barber, DH
Bossert, JM
Lupica, CR
Shaham, Y
Hope, BT
AF Cruz, Fabio C.
Koya, Eisuke
Guez-Barber, Danielle H.
Bossert, Jennifer M.
Lupica, Carl R.
Shaham, Yavin
Hope, Bruce T.
TI New technologies for examining the role of neuronal ensembles in drug
addiction and fear
SO NATURE REVIEWS NEUROSCIENCE
LA English
DT Article
ID NUCLEUS-ACCUMBENS NEURONS; STRESS-INDUCED REINSTATEMENT; PALATABLE FOOD
SEEKING; CONTEXT-SPECIFIC SENSITIZATION; HIPPOCAMPAL PLACE CELLS;
INDUCED GENE-REGULATION; IN-VIVO EXPERIENCE; FOS MESSENGER-RNA;
PREFRONTAL CORTEX; SYNAPTIC PLASTICITY
AB Correlational data suggest that learned associations are encoded within neuronal ensembles. However, it has been difficult to prove that neuronal ensembles mediate learned behaviours because traditional pharmacological and lesion methods, and even newer cell type-specific methods, affect both activated and non-activated neurons. In addition, previous studies on synaptic and molecular alterations induced by learning did not distinguish between behaviourally activated and non-activated neurons. Here, we describe three new approaches - Daun02 inactivation, FACS sorting of activated neurons and Fos-GFP transgenic rats - that have been used to selectively target and study activated neuronal ensembles in models of conditioned drug effects and relapse. We also describe two new tools - Fos-tTA transgenic mice and inactivation of CREB-overexpressing neurons - that have been used to study the role of neuronal ensembles in conditioned fear.
C1 [Cruz, Fabio C.; Koya, Eisuke; Guez-Barber, Danielle H.; Bossert, Jennifer M.; Lupica, Carl R.; Shaham, Yavin; Hope, Bruce T.] NIDA, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
RP Hope, BT (reprint author), NIDA, Intramural Res Program, NIH, 251 Bayview Blvd, Baltimore, MD 21224 USA.
EM bhope@intra.nida.nih.gov
RI Hope, Bruce/A-9223-2010; shaham, yavin/G-1306-2014
OI Hope, Bruce/0000-0001-5804-7061;
FU US National Institute on Drug Abuse, Intramural Research Program
FX The writing of this article was supported by the US National Institute
on Drug Abuse, Intramural Research Program. We thank the members of the
Hope, Lupica and Shaham laboratories who contributed to the development
and implementation of the new technologies described in this article.
NR 144
TC 49
Z9 49
U1 6
U2 48
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1471-003X
EI 1471-0048
J9 NAT REV NEUROSCI
JI Nat. Rev. Neurosci.
PD NOV
PY 2013
VL 14
IS 11
BP 743
EP 754
DI 10.1038/nrn3597
PG 12
WC Neurosciences
SC Neurosciences & Neurology
GA 238CS
UT WOS:000325918900007
PM 24088811
ER
PT J
AU Blair, RJR
AF Blair, R. James R.
TI The neurobiology of psychopathic traits in youths
SO NATURE REVIEWS NEUROSCIENCE
LA English
DT Review
ID CALLOUS-UNEMOTIONAL TRAITS; DISRUPTIVE BEHAVIOR DISORDERS; VENTROMEDIAL
PREFRONTAL CORTEX; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER;
POSTTRAUMATIC-STRESS-DISORDER; ONSET CONDUCT DISORDER; MATTER
MICROSTRUCTURAL ABNORMALITIES; ANTISOCIAL PERSONALITY-DISORDERS;
PROBABILISTIC RESPONSE REVERSAL; OPPOSITIONAL DEFIANT DISORDER
AB Conduct disorder is a childhood behaviour disorder that is characterized by persistent aggressive or antisocial behaviour that disrupts the child's environment and impairs his or her functioning. A proportion of children with conduct disorder have psychopathic traits. Psychopathic traits consist of a callous-unemotional component and an impulsive-antisocial component, which are associated with two core impairments. The first is a reduced empathic response to the distress of other individuals, which primarily reflects reduced amygdala responsiveness to distress cues; the second is deficits in decision making and in reinforcement learning, which reflects dysfunction in the ventromedial prefrontal cortex and striatum. Genetic and prenatal factors contribute to the abnormal development of these neural systems, and social-environmental variables that affect motivation influence the probability that antisocial behaviour will be subsequently displayed.
C1 NIMH, NIH, Bethesda, MD 20892 USA.
RP Blair, RJR (reprint author), NIMH, NIH, Bethesda, MD 20892 USA.
EM JamesBlair@mail.nih.gov
FU Intramural Research Program of the National Institute of Mental Health,
National Institutes of Health, USA [1-ZIA-MH002860-08]
FX This work was supported by the Intramural Research Program of the
National Institute of Mental Health, National Institutes of Health, USA,
under grant number 1-ZIA-MH002860-08.
NR 247
TC 104
Z9 104
U1 53
U2 173
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1471-003X
EI 1471-0048
J9 NAT REV NEUROSCI
JI Nat. Rev. Neurosci.
PD NOV
PY 2013
VL 14
IS 11
BP 786
EP 799
DI 10.1038/nrn3577
PG 14
WC Neurosciences
SC Neurosciences & Neurology
GA 238CS
UT WOS:000325918900010
PM 24105343
ER
PT J
AU Casey, BJ
Craddock, N
Cuthbert, BN
Hyman, SE
Lee, FS
Ressler, KJ
AF Casey, B. J.
Craddock, Nick
Cuthbert, Bruce N.
Hyman, Steven E.
Lee, Francis S.
Ressler, Kerry J.
TI DSM-5 and RDoC: progress in psychiatry research?
SO NATURE REVIEWS NEUROSCIENCE
LA English
DT Editorial Material
ID FUTURE
AB Neuroscience studies into psychiatric disorders generally rely on disease definitions that are based on the influential Diagnostic and Statistical Manual of Mental Disorders (DSM), the fifth edition of which (DSM-5) was released earlier this year. Designed as a purely diagnostic tool, the DSM considers different disorders as distinct entities. However, boundaries between disorders are often not as strict as the DSM suggests. To provide an alternative framework for research into psychiatric disorders, the US National Institute of Mental Health (NIMH) has recently introduced its Research Domain Criteria (RDoC) project. In the RDoC, five 'domains' each reflect a brain system in which functioning is impaired, to different degrees, in different psychiatric conditions. Nature Reviews Neuroscience asked six leading investigators for their thoughts on how DSM-5 and the RDoC will influence neuroscience research into psychiatric disorders.
C1 [Casey, B. J.] Cornell Univ, Weill Med Coll, Dept Psychiat, Inst Dev Psychobiol, New York, NY 10065 USA.
[Craddock, Nick] Cardiff Univ, Inst Psychol Med & Clin Neurosci, MRC, Ctr Neuropsychiat Genet & Genom, Cardiff CF24 4HQ, S Glam, Wales.
[Cuthbert, Bruce N.] NIMH, NIH, Bethesda, MD 20892 USA.
[Hyman, Steven E.] MIT, Stanley Ctr Psychiat Res, Broad Inst, Cambridge, MA 02142 USA.
[Hyman, Steven E.] Harvard Univ, Cambridge, MA 02142 USA.
[Lee, Francis S.] Cornell Univ, Weill Cornell Med Coll, Dept Psychiat, New York, NY 10065 USA.
[Lee, Francis S.] Cornell Univ, Weill Cornell Med Coll, Dept Pharmacol, New York, NY 10065 USA.
[Ressler, Kerry J.] Emory Univ, Howard Hughes Med Inst, Atlanta, GA 30329 USA.
[Ressler, Kerry J.] Emory Univ, Dept Psychiat & Behav Sci, Atlanta, GA 30329 USA.
RP Casey, BJ (reprint author), Cornell Univ, Weill Med Coll, Dept Psychiat, Inst Dev Psychobiol, New York, NY 10065 USA.
EM bjc2002@med.cornell.edu; craddockn@cardiff.ac.uk; bcuthber@mail.nih.gov;
stevehy@broadinstitute.org; fslee@med.cornell.edu; kressle@emory.edu
OI Ressler, Kerry/0000-0002-5158-1103
FU NIMH NIH HHS [P50 MH079513]; NINDS NIH HHS [R01 NS052819]
NR 6
TC 74
Z9 78
U1 1
U2 38
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1471-003X
EI 1471-0048
J9 NAT REV NEUROSCI
JI Nat. Rev. Neurosci.
PD NOV
PY 2013
VL 14
IS 11
BP 810
EP 814
DI 10.1038/nrn3621
PG 5
WC Neurosciences
SC Neurosciences & Neurology
GA 238CS
UT WOS:000325918900012
PM 24135697
ER
PT J
AU Magnus, MC
Stene, LC
Haberg, SE
Nafstad, P
Stigum, H
London, SJ
Nystad, W
AF Magnus, Maria C.
Stene, Lars C.
Haberg, Siri E.
Nafstad, Per
Stigum, Hein
London, Stephanie J.
Nystad, Wenche
TI Prospective Study of Maternal Mid-pregnancy 25-hydroxyvitamin D Level
and Early Childhood Respiratory Disorders
SO PAEDIATRIC AND PERINATAL EPIDEMIOLOGY
LA English
DT Article
DE asthma; lower respiratory tract infection; pregnancy; vitamin D
ID VITAMIN-D INTAKE; NORWEGIAN MOTHER; LUNG DEVELOPMENT; IMMUNE-SYSTEM; D
DEFICIENCY; ASTHMA; RISK; CHILDREN; COHORT; INFECTION
AB BackgroundStudies suggest that prenatal vitamin D status may be inversely associated with lower respiratory tract infections (LRTIs) early in life. Studies of prenatal vitamin D status and development of asthma have inconsistent findings.
MethodsWe examined the associations of maternal mid-pregnancy 25-hydroxyvitamin D [25(OH)D] level with the frequency of LRTIs by 36 months and with current asthma at 36 months using the Norwegian Mother and Child Cohort Study. Maternal plasma 25(OH)D level was measured using liquid chromatography-tandem mass spectrometry. Respiratory disorders were evaluated by maternal report through questionnaires. LRTIs were analysed in a random sample of 1248 children. Asthma was analysed using a case-control design, including 489 cases and 1183 controls. Multivariable generalised linear models calculated adjusted measures of association.
ResultsThe median gestational week of sample collection was 18 weeks (range 9, 35). The mean 25(OH)D level was 73.7nmol/L (standard deviation 23.7). Higher maternal mid-pregnancy 25(OH)D level was associated with a reduced risk of three or more LRTIs by 36 months vs. none, adjusted risk ratio 0.74 [95% confidence interval (CI): 0.58, 0.93] per 20nmol/L increase. Associations were similar when examining the frequency of LRTIs by 18 months, and the frequency of LRTIs between 18 and 36 months. Maternal mid-pregnancy 25(OH)D level was not significantly associated with current asthma at 36 months, adjusted odds ratio 0.91 [95% CI 0.81, 1.02] per 20nmol/L increase.
ConclusionsHigher maternal mid-pregnancy 25(OH)D level was associated with a modestly reduced risk of recurrent LRTIs by 36 months, but was not associated with current asthma at 36 months.
C1 [Magnus, Maria C.; Stene, Lars C.; Haberg, Siri E.; Nafstad, Per; Stigum, Hein; Nystad, Wenche] Norwegian Inst Publ Hlth, Dept Chron Dis, Div Epidemiol, N-0403 Oslo, Norway.
[Nafstad, Per; Stigum, Hein] Univ Oslo, Dept Community Med, Fac Med, Oslo, Norway.
[London, Stephanie J.] NIEHS, Epidemiol Branch, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
[London, Stephanie J.] NIEHS, Lab Resp Biol, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
RP Magnus, MC (reprint author), Norwegian Inst Publ Hlth, Dept Chron Dis, Div Epidemiol, POB 4404 Nydalen, N-0403 Oslo, Norway.
EM maria.christine.magnus@fhi.no
OI London, Stephanie/0000-0003-4911-5290
FU NIH (NIH/NIEHS) [ZIAES049019]; NIH (NIH/NINDS) [1 UO1 NS 047537-01, 2
UO1 NS 047537-06A1]; Norwegian Research Council/FUGE [151918/S10];
Norwegian Extra-Foundation for Health and Rehabilitation [2011.2.0218]
FX The Norwegian Mother and Child Cohort Study is supported by NIH
(NIH/NIEHS project number ZIAES049019, NIH/NINDS grant no.1 UO1 NS
047537-01 and grant no.2 UO1 NS 047537-06A1), in addition to a grant
from the Norwegian Research Council/FUGE (grant number 151918/S10). The
first author was further supported by a grant from the Norwegian
Extra-Foundation for Health and Rehabilitation (grant number
2011.2.0218). The authors are grateful to all the families participating
in the Norwegian Mother and Child Cohort Study.
NR 39
TC 19
Z9 19
U1 0
U2 12
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 2013
VL 27
IS 6
BP 532
EP 541
DI 10.1111/ppe.12080
PG 10
WC Public, Environmental & Occupational Health; Obstetrics & Gynecology;
Pediatrics
SC Public, Environmental & Occupational Health; Obstetrics & Gynecology;
Pediatrics
GA 238WZ
UT WOS:000325983800004
PM 24134527
ER
PT J
AU Nilsen, RM
Suren, P
Gunnes, N
Alsaker, ER
Bresnahan, M
Hirtz, D
Hornig, M
Lie, KK
Lipkin, WI
Reichborn-Kjennerud, T
Roth, C
Schjolberg, S
Smith, GD
Susser, E
Vollset, SE
Oyen, AS
Magnus, P
Stoltenberg, C
AF Nilsen, Roy M.
Suren, Pal
Gunnes, Nina
Alsaker, Elin R.
Bresnahan, Michaeline
Hirtz, Deborah
Hornig, Mady
Lie, Kari Kveim
Lipkin, W. Ian
Reichborn-Kjennerud, Ted
Roth, Christine
Schjolberg, Synnve
Smith, George Davey
Susser, Ezra
Vollset, Stein Emil
Oyen, Anne-Siri
Magnus, Per
Stoltenberg, Camilla
TI Analysis of Self-selection Bias in a Population-based Cohort Study of
Autism Spectrum Disorders
SO PAEDIATRIC AND PERINATAL EPIDEMIOLOGY
LA English
DT Article
DE Autism; cohort; Norway; pregnancy; selection bias
ID FOLIC-ACID SUPPLEMENTS; PERINATAL RISK-FACTORS; INFANTILE-AUTISM;
CHILDREN; PARTICIPATION; ASSOCIATION; PREVALENCE; REGISTRY; CHARGE;
DELAY
AB BackgroundThis study examined potential self-selection bias in a large pregnancy cohort by comparing exposure-outcome associations from the cohort to similar associations obtained from nationwide registry data. The outcome under study was specialist-confirmed diagnosis of autism spectrum disorders (ASDs).
MethodsThe cohort sample (n=89836) was derived from the population-based prospective Norwegian Mother and Child Cohort Study and its substudy of ASDs, the Autism Birth Cohort (ABC) study. The nationwide registry data were derived from the Medical Birth Registry of Norway (n=507856). The children were born in 1999-2007, and seven prenatal and perinatal exposures were selected for analyses.
ResultsASDs were reported for 234 (0.26%) children in the cohort and 2072 (0.41%) in the nationwide population. Compared with the nationwide population, the cohort had an under-representation of the youngest women (<25 years), those who had single status, mothers who smoked during pregnancy, and non-users of prenatal folic acid supplements. The ratios of the adjusted odds ratios (ORs) in the cohort over the adjusted ORs in the nationwide population were as follows; primipara pregnancy: 1.39/1.22, prenatal folic acid use: 0.85/0.86, prenatal smoking: 1.20/1.17, preterm birth (<37 weeks): 1.48/1.42, low birthweight (<2500g): 1.60/1.58, male sex: 4.39/4.59 (unadjusted only); and caesarean section history: 1.03/1.04.
ConclusionsAssociations estimated between ASDs and perinatal and prenatal exposures in the cohort are close to those estimated in the nationwide population. Self-selection does not appear to compromise validity of exposure-outcome associations in the ABC study.
C1 [Nilsen, Roy M.; Vollset, Stein Emil; Stoltenberg, Camilla] Univ Bergen, Dept Global Publ Hlth & Primary Care, N-5018 Bergen, Norway.
[Reichborn-Kjennerud, Ted] Univ Oslo, Inst Psychiat, N-0316 Oslo, Norway.
[Oyen, Anne-Siri] Lovisenberg Hosp, Nic Waals Inst, Oslo, Norway.
[Bresnahan, Michaeline; Hornig, Mady; Lipkin, W. Ian; Susser, Ezra] Columbia Univ, Mailman Sch Publ Hlth, New York, NY USA.
[Hirtz, Deborah] NINDS, Bethesda, MD 20892 USA.
[Smith, George Davey] Univ Bristol, MRC Integrat Epidemiol Unit IEU, Bristol, Avon, England.
RP Nilsen, RM (reprint author), Univ Bergen, Dept Global Publ Hlth & Primary Care, Kalfarveien 31, N-5018 Bergen, Norway.
EM roy.nilsen@uib.no
RI Davey Smith, George/A-7407-2013
OI Davey Smith, George/0000-0002-1407-8314
FU Norwegian Ministry of Health and Care Services; Norwegian Ministry of
Education and Research; Research Council of Norway/FUGE [151918];
National Institute of Neurological Disorders and Stroke (NIH/NINDS),
Bethesda, MD, USA [NS47537]; National Institute of Environmental Health
Sciences (NIH/NIEHS), Research Triangle Park, NC, USA [NO-ES-75558];
NINDS [NS47537]; Faculty of Medicine and Dentistry, University of
Bergen, Norway
FX The authors are indebted to Ane Johannessen for her valuable comments on
previous versions of this manuscript. The Norwegian Mother and Child
Cohort Study is supported by the Norwegian Ministry of Health and Care
Services, the Norwegian Ministry of Education and Research, the Research
Council of Norway/FUGE (grant 151918), the National Institute of
Neurological Disorders and Stroke (NIH/NINDS), Bethesda, MD, USA [grant
NS47537 (Lipkin)], and the National Institute of Environmental Health
Sciences (NIH/NIEHS), Research Triangle Park, NC, USA (contract
NO-ES-75558). The Autism Birth Cohort study is funded by the NINDS
[grant NS47537 (Lipkin)]. The current work was supported by the Faculty
of Medicine and Dentistry, University of Bergen, Norway.
NR 30
TC 27
Z9 27
U1 3
U2 14
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 2013
VL 27
IS 6
BP 553
EP 563
DI 10.1111/ppe.12077
PG 11
WC Public, Environmental & Occupational Health; Obstetrics & Gynecology;
Pediatrics
SC Public, Environmental & Occupational Health; Obstetrics & Gynecology;
Pediatrics
GA 238WZ
UT WOS:000325983800006
PM 23919580
ER
PT J
AU Schisterman, EF
Silver, RM
Perkins, NJ
Mumford, SL
Whitcomb, BW
Stanford, JB
Lesher, LL
Faraggi, D
Wactawski-Wende, J
Browne, RW
Townsend, JM
White, M
Lynch, AM
Galai, N
AF Schisterman, Enrique F.
Silver, Robert M.
Perkins, Neil J.
Mumford, Sunni L.
Whitcomb, Brian W.
Stanford, Joseph B.
Lesher, Laurie L.
Faraggi, David
Wactawski-Wende, Jean
Browne, Richard W.
Townsend, Janet M.
White, Mark
Lynch, Anne M.
Galai, Noya
TI A Randomised Trial to Evaluate the Effects of Low-dose Aspirin in
Gestation and Reproduction: Design and Baseline Characteristics
SO PAEDIATRIC AND PERINATAL EPIDEMIOLOGY
LA English
DT Article
DE low-dose aspirin; conception; pregnancy; miscarriage; subfertility
ID RECURRENT MISCARRIAGE; PREGNANCY; WOMEN; PREVENTION; HEPARIN; WEIGHT
AB BackgroundLow-dose aspirin (LDA) has been proposed to improve pregnancy outcomes in couples experiencing recurrent pregnancy loss. However, results from studies of LDA on pregnancy outcomes have been inconsistent, perhaps because most studies evaluated LDA-initiated post-conception. The purpose of the Effects of Aspirin in Gestation and Reproduction (EAGeR) trial was to determine whether preconception-initiated LDA improves livebirth rates in women with one to two prior losses.
MethodsWe performed a multicentre, block randomised, double-blind, placebo-controlled trial. Study participants were recruited using community-based advertisements and physician referral to four university medical centres in the US (2006-12). Eligible women were aged 18-40 years actively trying to conceive, with one to two prior losses. Participants were randomised to receive daily LDA (81mg/day) or a matching placebo, and all were provided with daily 400-mcg folic acid. Follow-up continued for 6 menstrual cycles while attempting to conceive. For those who conceived, treatment was continued until 36 weeks gestation. The primary outcome was the cumulative livebirth rate over the trial period.
ResultsThere were 1228 women randomised (615 LDA, 613 placebo). Participants had a mean age of 28.7, were mostly white (95%), well educated (86%more thanhigh school education), and employed (75%) with a household income >$100000 annually (40%). The characteristics of those in the treatment and placebo arms were well balanced.
ConclusionsWe describe the study design, recruitment, data collection, and baseline characteristics of participants enrolled in EAGeR, which aimed to determine the effect of LDA on livebirth and other pregnancy outcomes in these women.
C1 [Schisterman, Enrique F.; Perkins, Neil J.; Mumford, Sunni L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Intramural Populat Hlth Res, Rockville, MD 20854 USA.
[Silver, Robert M.; Stanford, Joseph B.; Lesher, Laurie L.] Univ Utah, Dept Obstet & Gynecol, Salt Lake City, UT USA.
[Stanford, Joseph B.] Univ Utah, Dept Family & Prevent Med, Salt Lake City, UT USA.
[Whitcomb, Brian W.] Univ Massachusetts, Sch Publ Hlth & Hlth Sci, Div Biostat & Epidemiol, Amherst, MA 01003 USA.
[Wactawski-Wende, Jean] SUNY Buffalo, Dept Social & Prevent Med, Buffalo, NY 14260 USA.
[Browne, Richard W.] SUNY Buffalo, Dept Biotech & Clin Lab Sci, Buffalo, NY 14260 USA.
[Townsend, Janet M.; White, Mark] Commonwealth Med Coll, Dept Family Community & Rural Hlth, Scranton, PA USA.
[Lynch, Anne M.] Univ Colorado, Dept Obstet & Gynecol, Denver, CO 80202 USA.
[Faraggi, David; Galai, Noya] Univ Haifa, Dept Stat, IL-31999 Haifa, Israel.
RP Schisterman, EF (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, 6100 Execut Blvd,7B03, Rockville, MD 20854 USA.
EM schistee@mail.nih.gov
OI Perkins, Neil/0000-0002-6802-4733; 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, Bethesda, Maryland [HHSN267200603423, HHSN267200603424,
HHSN267200603426]
FX This research was supported by the Intramural Research Program of the
Eunice Kennedy Shriver National Institute of Child Health and Human
Development, National Institutes of Health, Bethesda, Maryland (Contract
Nos. HHSN267200603423, HHSN267200603424, HHSN267200603426). We would
like to especially thank the EAGeR participants for their extraordinary
commitment to the study, all of the EAGeR investigators and staff who
devoted their time and energy to the success of this trial, and the Data
Safety and Monitoring Board members for ongoing oversight, constant
support, and advice throughout the trial.
NR 17
TC 19
Z9 19
U1 0
U2 15
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 2013
VL 27
IS 6
BP 598
EP 609
DI 10.1111/ppe.12088
PG 12
WC Public, Environmental & Occupational Health; Obstetrics & Gynecology;
Pediatrics
SC Public, Environmental & Occupational Health; Obstetrics & Gynecology;
Pediatrics
GA 238WZ
UT WOS:000325983800010
PM 24118062
ER
PT J
AU Smith, SM
Dart, RC
Katz, NP
Paillard, F
Adams, EH
Comer, SD
Degroot, A
Edwards, RR
Haddox, JD
Jaffe, JH
Jones, CM
Kleber, HD
Kopecky, EA
Markman, JD
Montoya, ID
O'Brien, C
Roland, CL
Stanton, M
Strain, EC
Vorsanger, G
Wasan, AD
Weiss, RD
Turk, DC
Dworkin, RH
AF Smith, Shannon M.
Dart, Richard C.
Katz, Nathaniel P.
Paillard, Florence
Adams, Edgar H.
Comer, Sandra D.
Degroot, Aldemar
Edwards, Robert R.
Haddox, J. David
Jaffe, Jerome H.
Jones, Christopher M.
Kleber, Herbert D.
Kopecky, Ernest A.
Markman, John D.
Montoya, Ivan D.
O'Brien, Charles
Roland, Carl L.
Stanton, Marsha
Strain, Eric C.
Vorsanger, Gary
Wasan, Ajay D.
Weiss, Roger D.
Turk, Dennis C.
Dworkin, Robert H.
TI Classification and definition of misuse, abuse, and related events in
clinical trials: ACTTION systematic review and recommendations
SO PAIN
LA English
DT Review
DE Classification; Clinical trials; Prescription drug abuse; Prescription
drug misuse; Systematic review
ID AMERICAN ASSOCIATION; ADVERSE EVENTS; OPIOID THERAPY; CHRONIC PAIN;
ADDICTION; DEPENDENCE; DIVERSION; ADOLESCENTS
AB As the nontherapeutic use of prescription medications escalates, serious associated consequences have also increased. This makes it essential to estimate misuse, abuse, and related events (MAREs) in the development and postmarketing adverse event surveillance and monitoring of prescription drugs accurately. However, classifications and definitions to describe prescription drug MAREs differ depending on the purpose of the classification system, may apply to single events or ongoing patterns of inappropriate use, and are not standardized or systematically employed, thereby complicating the ability to assess MARE occurrence adequately. In a systematic review of existing prescription drug MARE terminology and definitions from consensus efforts, review articles, and major institutions and agencies, MARE terms were often defined inconsistently or idiosyncratically, or had definitions that overlapped with other MARE terms. The Analgesic, Anesthetic, and Addiction Clinical Trials, Translations, Innovations, Opportunities, and Networks (ACTTION) public-private partnership convened an expert panel to develop mutually exclusive and exhaustive consensus classifications and definitions of MAREs occurring in clinical trials of analgesic medications to increase accuracy and consistency in characterizing their occurrence and prevalence in clinical trials. The proposed ACTTION classifications and definitions are designed as a first step in a system to adjudicate MAREs that occur in analgesic clinical trials and postmarketing adverse event surveillance and monitoring, which can be used in conjunction with other methods of assessing a treatment's abuse potential. (C) 2013 International Association for the Study of Pain. Published by Elsevier B. V. All rights reserved.
C1 [Smith, Shannon M.; Dworkin, Robert H.] Univ Rochester, Sch Med & Dent, Dept Anesthesiol, Rochester, NY 14627 USA.
[Dart, Richard C.] Univ Colorado, Sch Med, Denver, CO USA.
[Dart, Richard C.] Denver Hlth, Rocky Mt Poison & Drug Ctr, Denver, CO USA.
[Katz, Nathaniel P.] Analges Solut, Natick, MA USA.
[Katz, Nathaniel P.; Haddox, J. David] Tufts Univ, Boston, MA 02111 USA.
[Paillard, Florence] Focus Biocom, Durango, CO USA.
[Adams, Edgar H.] Covance Market Access, Gaithersburg, MD USA.
[Comer, Sandra D.; Kleber, Herbert D.] Columbia Univ, New York State Psychiat Inst, New York, NY USA.
[Degroot, Aldemar] Astellas Pharma Inc, Northbrook, IL USA.
[Edwards, Robert R.] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Haddox, J. David] Purdue Pharma LP, Stamford, CT USA.
[Jaffe, Jerome H.] Univ Maryland, Sch Med, Baltimore, MD 21201 USA.
[Jones, Christopher M.] Ctr Dis Control & Prevent, Atlanta, GA USA.
[Kopecky, Ernest A.] Collegium Pharmaceut Inc, Canton, MA USA.
[Markman, John D.] Univ Rochester, Dept Neurosurg, Rochester, NY USA.
[Montoya, Ivan D.] NIDA, Bethesda, MD 20892 USA.
[O'Brien, Charles] Univ Penn, Philadelphia, PA 19104 USA.
[Roland, Carl L.] Pfizer Inc, Cary, NC USA.
[Stanton, Marsha] Horizon Pharma Inc, Deerfield, IL USA.
[Strain, Eric C.] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA.
[Vorsanger, Gary] Janssen Sci Affairs LLC, Raritan, NJ USA.
[Wasan, Ajay D.] Harvard Univ, Sch Med, Chestnut Hill, MA USA.
[Weiss, Roger D.] Harvard Univ, Sch Med, Boston, MA USA.
[Weiss, Roger D.] McLean Hosp, Div Alcohol & Drug Abuse, Belmont, MA 02178 USA.
[Turk, Dennis C.] Univ Washington, Dept Anesthesiol & Pain Med, Seattle, WA 98195 USA.
[Dworkin, Robert H.] Univ Rochester, Sch Med & Dent, Dept Neurol, Rochester, NY 14642 USA.
[Dworkin, Robert H.] Univ Rochester, Sch Med & Dent, Ctr Human Expt Therapeut, Rochester, NY USA.
RP Smith, SM (reprint author), Univ Rochester, Sch Med & Dent, Dept Anesthesiol, Rochester, NY 14627 USA.
EM shannon1_smith@urmc.rochester.edu
RI bebarta, vikhyat/K-3476-2015
FU U.S. Food and Drug Administration, the Centers for Disease Control and
Prevention; ACTTION; U.S. Food and Drug Administration; National
Institute on Drug Abuse [DA09236, DA031022, DA16759, K23 DA020681]
FX The findings, conclusions, and recommendations contained in this report
are those of the authors. No official endorsement by the U.S. Food and
Drug Administration, the Centers for Disease Control and Prevention, or
the pharmaceutical companies that provided unrestricted grants to
support the activities of ACTTION should be inferred. Financial support
for this study was provided by ACTTION, which has received research
contracts, grants, or other revenue from the U.S. Food and Drug
Administration, various pharmaceutical companies, and other sources.
This work was also supported by Grants DA09236, DA031022, and DA16759
(to Sandra D. Comer), Grant K23 DA020681 (to Ajay D. Wasan), and Grant
K24 DA022288 (to Roger D. Weiss) from the National Institute on Drug
Abuse.
NR 43
TC 54
Z9 54
U1 0
U2 17
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0304-3959
EI 1872-6623
J9 PAIN
JI Pain
PD NOV
PY 2013
VL 154
IS 11
BP 2287
EP 2296
DI 10.1016/j.pain.2013.05.053
PG 10
WC Anesthesiology; Clinical Neurology; Neurosciences
SC Anesthesiology; Neurosciences & Neurology
GA 238FG
UT WOS:000325927500010
PM 23792283
ER
PT J
AU O'Connor, AB
Turk, DC
Dworkin, RH
Katz, NP
Colucci, R
Haythornthwaite, JA
Klein, M
O'Brien, C
Posner, K
Rappaport, BA
Reisfield, G
Adams, EH
Balster, RL
Bigelow, GE
Burke, LB
Comer, SD
Cone, E
Cowan, P
Denisco, RA
Farrar, JT
Foltin, RW
Haddox, JD
Hertz, S
Jay, GW
Junor, R
Kopecky, EA
Leiderman, DB
McDermott, MP
Palmer, PP
Raja, SN
Rauschkolb, C
Rowbotham, MC
Sampaio, C
Setnik, B
Smith, SM
Sokolowska, M
Stauffer, JW
Walsh, SL
Zacny, JP
AF O'Connor, Alec B.
Turk, Dennis C.
Dworkin, Robert H.
Katz, Nathaniel P.
Colucci, Robert
Haythornthwaite, Jennifer A.
Klein, Michael
O'Brien, Charles
Posner, Kelly
Rappaport, Bob A.
Reisfield, Gary
Adams, Edgar H.
Balster, Robert L.
Bigelow, George E.
Burke, Laurie B.
Comer, Sandra D.
Cone, Edward
Cowan, Penney
Denisco, Richard A.
Farrar, John T.
Foltin, Richard W.
Haddox, J. David
Hertz, Sharon
Jay, Gary W.
Junor, Roderick
Kopecky, Ernest A.
Leiderman, Deborah B.
McDermott, Michael P.
Palmer, Pamela P.
Raja, Srinivasa N.
Rauschkolb, Christine
Rowbotham, Michael C.
Sampaio, Cristina
Setnik, Beatrice
Smith, Shannon M.
Sokolowska, Marta
Stauffer, Joseph W.
Walsh, Sharon L.
Zacny, James P.
TI Abuse liability measures for use in analgesic clinical trials in
patients with pain: IMMPACT recommendations
SO PAIN
LA English
DT Article
DE Abuse; Abuse liability; Clinical trial; Opioids; Prescription drug
abuse; Risk of abuse; Study design
ID CHRONIC OPIOID THERAPY; CHRONIC NONCANCER PAIN; ABERRANT DRUG BEHAVIOR;
CORE OUTCOME MEASURES; CROSS-VALIDATION; MISUSE MEASURE; UNITED-STATES;
SOAPP-R; RISK; SCREENER
AB Assessing and mitigating the abuse liability (AL) of analgesics is an urgent clinical and societal problem. Analgesics have traditionally been assessed in randomized clinical trials (RCTs) designed to demonstrate analgesic efficacy relative to placebo or an active comparator. In these trials, rigorous, prospectively designed assessment for AL is generally not performed. The Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) convened a consensus meeting to review the available evidence and discuss methods for improving the assessment of the AL of analgesics in clinical trials in patients with pain. Recommendations for improved assessment include: (1) performing trials that include individuals with diverse risks of abuse; (2) improving the assessment of AL in clinical trials (eg, training study personnel in the principles of abuse and addiction behaviors, designing the trial to assess AL outcomes as primary or secondary outcome measures depending on the trial objectives); (3) performing standardized assessment of outcomes, including targeted observations by study personnel and using structured adverse events query forms that ask all subjects specifically for certain symptoms (such as euphoria and craving); and (4) collecting detailed information about events of potential concern (eg, unexpected urine drug testing results, loss of study medication, and dropping out of the trial). The authors also propose a research agenda for improving the assessment of AL in future trials. (C) 2013 International Association for the Study of Pain. Published by Elsevier B. V. All rights reserved.
C1 [O'Connor, Alec B.] Univ Rochester, Dept Med, Rochester, NY USA.
[Turk, Dennis C.] Univ Washington, Dept Anesthesiol & Pain Med, Seattle, WA 98195 USA.
[Dworkin, Robert H.] Univ Rochester, Dept Anesthesiol, Rochester, NY USA.
[Katz, Nathaniel P.] Analges Solut, Natick, MA USA.
[Katz, Nathaniel P.] Tufts Univ, Sch Med, Dept Anesthesiol, Boston, MA 02111 USA.
[Colucci, Robert] Colucci & Associates LLC, Newtown, CT USA.
[Haythornthwaite, Jennifer A.; Bigelow, George E.; Cone, Edward] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA.
[Klein, Michael; Rappaport, Bob A.; Burke, Laurie B.; Hertz, Sharon] US FDA, Silver Spring, MD USA.
[O'Brien, Charles] Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA.
[Posner, Kelly; Comer, Sandra D.; Foltin, Richard W.] Columbia Univ, Coll Phys & Surg, New York State Psychiat Inst, Ctr Suicide Risk Assessment, New York, NY USA.
[Reisfield, Gary] Univ Florida, Dept Psychiat, Coll Med, Gainesville, FL 32611 USA.
[Adams, Edgar H.] Covance, Princeton, NJ USA.
[Balster, Robert L.] Virginia Commonwealth Univ, Inst Drug & Alcohol Studies, Richmond, VA USA.
[Cowan, Penney] Amer Chron Pain Assoc, Rocklin, CA USA.
[Denisco, Richard A.] NIDA, Rockville, MD USA.
[Farrar, John T.] Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA.
[Haddox, J. David] Purdue Pharma LP, Stamford, CT USA.
[Haddox, J. David] Tufts Univ, Sch Med, Dept Publ Hlth & Community Med, Boston, MA 02111 USA.
[Jay, Gary W.] Pfizer Inc, Ann Arbor, MI USA.
[Junor, Roderick] Eisai Ltd, Woodcliff Lake, NJ USA.
[Kopecky, Ernest A.] Endo Pharmaceut Inc, Chadds Ford, PA USA.
[Leiderman, Deborah B.] CNS Drug Consulting LLC, Mclean, VA USA.
[McDermott, Michael P.] Univ Rochester, Dept Biostat & Computat Biol, Rochester, NY USA.
[Palmer, Pamela P.] AcelRx Pharmaceut Inc, Redwood City, CA USA.
[Raja, Srinivasa N.] Johns Hopkins Univ, Baltimore Sch Med, Dept Anesthesiol & Crit Care Med, Baltimore, MD 21218 USA.
[Rauschkolb, Christine] Johnson & Johnson Pharmaceut Res & Dev LLC, Raritan, NJ USA.
[Rowbotham, Michael C.] Calif Pacific Med Ctr, Res Inst, San Francisco, CA USA.
[Sampaio, Cristina] Fac Med Lisbon, Clin Pharmacol & Therapeut Lab, Lisbon, Portugal.
[Setnik, Beatrice; Smith, Shannon M.] King Pharmaceut Inc, Cary, NC USA.
[Sokolowska, Marta] Grunenthal USA Inc, Bedminster, NJ USA.
[Stauffer, Joseph W.] Durect Corp, Cupertino, CA USA.
[Walsh, Sharon L.] Univ Kentucky, Ctr Drug & Alcohol Res, Dept Behav Sci, Lexington, KY 40506 USA.
[Zacny, James P.] Univ Chicago, Dept Anesthesia & Crit Care, Chicago, IL 60637 USA.
RP Turk, DC (reprint author), Univ Washington, Dept Anesthesiol & Pain Med, Box 356540, Seattle, WA 98195 USA.
EM turkdc@uw.edu
OI Yang, Shuman/0000-0002-9638-0890
FU University of Rochester Office of Continuing Professional Education
FX The views expressed in this article are those of the authors, none of
whom have financial conflicts of interest related to the specific issues
discussed herein. At the time of the consensus meeting on which this
article is based, 9 of the authors were employed by one of the companies
that provided unrestricted grants to the University of Rochester Office
of Continuing Professional Education to support the activities of
IMMPACT, including the consensus meeting; these companies were AcelRx,
Durect, Eisai, Endo, Grunenthal, Johnson & Johnson, King, Pfizer, and
Purdue Pharma LP. No official endorsement by the U.S. Food and Drug
Administration, U.S. National Institutes of Health, or the
pharmaceutical companies that provided unrestricted grants to the
University of Rochester Office of Continuing Professional Education
should be inferred.
NR 58
TC 14
Z9 14
U1 5
U2 17
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0304-3959
EI 1872-6623
J9 PAIN
JI Pain
PD NOV
PY 2013
VL 154
IS 11
BP 2324
EP 2334
DI 10.1016/j.pain.2013.06.035
PG 11
WC Anesthesiology; Clinical Neurology; Neurosciences
SC Anesthesiology; Neurosciences & Neurology
GA 238FG
UT WOS:000325927500014
PM 24148704
ER
PT J
AU Slade, GD
Smith, SB
Zaykin, DV
Tchivileva, IE
Gibson, DG
Yuryev, A
Mazo, I
Bair, E
Fillingim, R
Ohrbach, R
Greenspan, J
Maixner, W
Diatchenko, L
AF Slade, Gary D.
Smith, Shad B.
Zaykin, Dmitri V.
Tchivileva, Inna E.
Gibson, Dustin G.
Yuryev, Anton
Mazo, Ilya
Bair, Eric
Fillingim, Roger
Ohrbach, Richard
Greenspan, Joel
Maixner, William
Diatchenko, Luda
TI Facial pain with localized and widespread manifestations: Separate
pathways of vulnerability
SO PAIN
LA English
DT Article
DE Temporomandibular disorder; Human genetics; Serotonergic receptor;
Case-control study
ID EXPERIMENTALLY EVOKED PAIN; T-CELL INFILTRATION; COMBINING P-VALUES;
TEMPOROMANDIBULAR DISORDERS; NEUROPATHIC PAIN; PALPATION TENDERNESS;
SPINAL-CORD; SEROTONIN; OPPERA; RISK
AB Human association studies of common genetic polymorphisms have identified many loci that are associated with risk of complex diseases, although individual loci typically have small effects. However, by envisaging genetic associations in terms of cellular pathways, rather than any specific polymorphism, combined effects of many biologically relevant alleles can be detected. The effects are likely to be most apparent in investigations of phenotypically homogenous subtypes of complex diseases. We report findings from a case-control, genetic association study of relationships between 2925 single nucleotide polymorphisms (SNPs) and 2 subtypes of a commonly occurring chronic facial pain condition, temporomandibular disorder (TMD): 1) localized TMD and 2) TMD with widespread pain. When compared to healthy controls, cases with localized TMD differed in allelic frequency of SNPs that mapped to a serotonergic receptor pathway (P = 0.0012), while cases of TMD with widespread pain differed in allelic frequency of SNPs that mapped to a T-cell receptor pathway (P = 0.0014). A risk index representing combined effects of 6 SNPs from the serotonergic pathway was associated with greater odds of localized TMD (odds ratio 2.7, P = 1.3 E-09), and the result was reproduced in a replication case-control cohort study of 639 people (odds ratio 1.6, P = 0.014). A risk index representing combined effects of 8 SNPs from the T-cell receptor pathway was associated with greater odds of TMD with widespread pain (P = 1.9 E-08), although the result was not significant in the replication cohort. These findings illustrate potential for clinical classification of chronic pain based on distinct molecular profiles and genetic background. (C) 2013 International Association for the Study of Pain. Published by Elsevier B. V. All rights reserved.
C1 [Slade, Gary D.; Smith, Shad B.; Tchivileva, Inna E.; Gibson, Dustin G.; Bair, Eric; Maixner, William; Diatchenko, Luda] Univ N Carolina, Reg Ctr Neurosensory Disorders, Chapel Hill, NC 27599 USA.
[Slade, Gary D.] Univ N Carolina, Dept Dent Ecol, Chapel Hill, NC 27599 USA.
[Slade, Gary D.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27599 USA.
[Zaykin, Dmitri V.] NIEHS, Res Triangle Pk, NC 27709 USA.
[Yuryev, Anton; Mazo, Ilya] Ariadne Diagnost LLC, Rockville, MD USA.
[Fillingim, Roger] Univ Florida, Dept Community Dent & Behav Sci, Gainesville, FL USA.
[Ohrbach, Richard] SUNY Buffalo, Dept Oral Diagnost Sci, Buffalo, NY 14260 USA.
[Greenspan, Joel] Univ Maryland, Sch Dent, Baltimore, MD 21201 USA.
RP Slade, GD (reprint author), Univ N Carolina, Reg Ctr Neurosensory Disorders, Chapel Hill, NC 27599 USA.
EM gary_slade@dentistry.unc.edu
RI Mazo, Ilya/G-6549-2014;
OI Mazo, Ilya/0000-0002-8587-4895; Gibson, Dustin/0000-0002-9073-3376;
Bair, Eric/0000-0001-8733-7869; Greenspan, Joel/0000-0003-4062-9797
FU National Institutes of Health, National Institutes of Dental and Cranial
Research [RO1-DE16558, UO1-DE017018]; Intramural Research Program of the
National Institutes of Health, National Institute of Environmental
Health Sciences
FX This work was supported by the National Institutes of Health, National
Institutes of Dental and Cranial Research (grant numbers RO1-DE16558 and
UO1-DE017018 to L. D., G. S., W. M.). D.V.Z was supported by the
Intramural Research Program of the National Institutes of Health,
National Institute of Environmental Health Sciences. We are grateful to
investigators at OPPERA study sites for their contribution in directing
data collection: Dr. Joel Greenspan, University of Maryland, Baltimore,
MD; Mr. Charles Knott, Battelle Memorial Inc, Durham, NC.
NR 50
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PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0304-3959
EI 1872-6623
J9 PAIN
JI Pain
PD NOV
PY 2013
VL 154
IS 11
BP 2335
EP 2343
DI 10.1016/j.pain.2013.07.009
PG 9
WC Anesthesiology; Clinical Neurology; Neurosciences
SC Anesthesiology; Neurosciences & Neurology
GA 238FG
UT WOS:000325927500015
PM 23867732
ER
PT J
AU Ramsden, CE
Faurot, KR
Zamora, D
Suchindran, CM
MacIntosh, BA
Gaylord, S
Ringel, A
Hibbeln, JR
Feldstein, AE
Mori, TA
Barden, A
Lynch, C
Coble, R
Mas, E
Palsson, O
Barrow, DA
Mann, JD
AF Ramsden, Christopher E.
Faurot, Keturah R.
Zamora, Daisy
Suchindran, Chirayath M.
MacIntosh, Beth A.
Gaylord, Susan
Ringel, Amit
Hibbeln, Joseph R.
Feldstein, Ariel E.
Mori, Trevor A.
Barden, Anne
Lynch, Chanee
Coble, Rebecca
Mas, Emilie
Palsson, Olafur
Barrow, David A.
Mann, J. Douglas
TI Targeted alteration of dietary n-3 and n-6 fatty acids for the treatment
of chronic headaches: A randomized trial
SO PAIN
LA English
DT Article
DE Omega-3; Omega-6; Headache; Migraine; Clinical trial
ID LINOLEIC-ACID; PSYCHOMETRIC PROPERTIES; INFLAMMATORY PAIN; PROSTAGLANDIN
E-2; CHRONIC MIGRAINE; SPINAL-CORD; METABOLITES; PRODUCTS; PLACEBO;
IMPACT
AB Omega-3 and n-6 fatty acids are biosynthetic precursors to lipid mediators with antinociceptive and pronociceptive properties. We conducted a randomized, single-blinded, parallel-group clinical trial to assess clinical and biochemical effects of targeted alteration in dietary n-3 and n-6 fatty acids for treatment of chronic headaches. After a 4-week preintervention phase, ambulatory patients with chronic daily headache undergoing usual care were randomized to 1 of 2 intensive, food-based 12-week dietary interventions: a high n-3 plus low n-6 (H3-L6) intervention, or a low n-6 (L6) intervention. Clinical outcomes included the Headache Impact Test (HIT-6, primary clinical outcome), Headache Days per month, and Headache Hours per day. Biochemical outcomes included the erythrocyte n-6 in highly unsaturated fatty acids (HUFA) score (primary biochemical outcome) and bioactive n-3 and n-6 derivatives. Fifty-six of 67 patients completed the intervention. Both groups achieved targeted intakes of n-3 and n-6 fatty acids. In intention-to-treat analysis, the H3-L6 intervention produced significantly greater improvement in the HIT-6 score (-7.5 vs -2.1; P < 0.001) and the number of Headache Days per month (-8.8 vs -4.0; P = 0.02), compared to the L6 group. The H3-L6 intervention also produced significantly greater reductions in Headache Hours per day (4.6 vs 1.2; P = 0.01) and the n-6 in HUFA score (21.0 vs 4.0%; P < 0.001), and greater increases in antinociceptive n-3 pathway markers 18-hydroxy-eicosapentaenoic acid (+118.4 vs +61.1%; P < 0.001) and 17-hydroxy-docosahexaenoic acid (+170.2 vs +27.2; P < 0.001). A dietary intervention increasing n-3 and reducing n-6 fatty acids reduced headache pain, altered antinociceptive lipid mediators, and improved quality-of-life in this population. Published by Elsevier B.V. on behalf of International Association for the Study of Pain.
C1 [Ramsden, Christopher E.; Ringel, Amit; Hibbeln, Joseph R.] NIAAA, Lab Membrane Biochem & Biophys, NIH, Bethesda, MD 20892 USA.
[Ramsden, Christopher E.; Faurot, Keturah R.; Zamora, Daisy; Gaylord, Susan; Lynch, Chanee; Coble, Rebecca; Mann, J. Douglas] Univ N Carolina, Program Integrat Med, Dept Phys Med & Rehabil, Chapel Hill, NC 27515 USA.
[Suchindran, Chirayath M.] Univ N Carolina, Sch Publ Hlth, Dept Biostat, Chapel Hill, NC USA.
[MacIntosh, Beth A.] Univ N Carolina, North Carolina Translat Clin Sci Inst, Nutr Res & Metab Core, Chapel Hill, NC USA.
[Feldstein, Ariel E.] Univ Calif San Diego, Dept Pediat Gastroenterol Hepatol & Nutr, San Diego, CA 92103 USA.
[Mori, Trevor A.; Barden, Anne; Mas, Emilie] Univ Western Australia, Royal Perth Hosp, Sch Med & Pharmacol, Perth, WA 6009, Australia.
[Palsson, Olafur] Univ N Carolina, Div Gastroenterol & Hepatol, Chapel Hill, NC USA.
[Barrow, David A.] Univ N Carolina, Sch Dent, Chapel Hill, NC USA.
[Mann, J. Douglas] Univ N Carolina, Dept Neurol, Chapel Hill, NC USA.
RP Ramsden, CE (reprint author), NIAAA, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM chris.ramsden@nih.gov
FU Mayday Fund; UNC Research Fellowship in Complementary and Alternative
Medicine (National Center for Complementary and Alternative Medicine
[NCCAM], National Institutes of Health [NIH]) [T32-AT003378]; North
Carolina Clinical and Translational Sciences Institute (National Center
for Research Resources [NCRR], NIH) [UL1RR025747]; UNC Nutrition Obesity
Research Center, CHAI Core (National Institute of Diabetes and Digestive
and Kidney Diseases [NIDDK], NIH) [DK056350]; National Institute on
Alcohol Abuse and Alcoholism, National Institutes of Health
FX The authors thank the patients who participated in the trial, and
acknowledge the following individuals for their research assistance:
Marjorie Busby for expertise with study design; Beth Fowler, Carol Carr,
Regina McCoy, and Tim McCaskill for design and functionality of the
study Website; Meg Mangan for 24-hour recall data collection and
management; Jim Loewke and Duk Hyun for fatty acid analyses; and Sharon
Majchrzak-Hong for data management support. This project was supported
by the Mayday Fund (primary source); the UNC Research Fellowship in
Complementary and Alternative Medicine (grant T32-AT003378, National
Center for Complementary and Alternative Medicine [NCCAM], National
Institutes of Health [NIH]); the North Carolina Clinical and
Translational Sciences Institute (grant UL1RR025747, National Center for
Research Resources [NCRR], NIH); the UNC Nutrition Obesity Research
Center, CHAI Core (grant DK056350, National Institute of Diabetes and
Digestive and Kidney Diseases [NIDDK], NIH); and the National Institute
on Alcohol Abuse and Alcoholism, National Institutes of Health. The
content is solely the responsibility of the authors and does not
necessarily represent the official views of the National Institutes of
Health.
NR 61
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PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0304-3959
EI 1872-6623
J9 PAIN
JI Pain
PD NOV
PY 2013
VL 154
IS 11
BP 2441
EP 2451
DI 10.1016/j.pain.2013.07.028
PG 11
WC Anesthesiology; Clinical Neurology; Neurosciences
SC Anesthesiology; Neurosciences & Neurology
GA 238FG
UT WOS:000325927500027
PM 23886520
ER
PT J
AU Colloca, L
Klinger, R
Flor, H
Bingel, U
AF Colloca, Luana
Klinger, Regine
Flor, Herta
Bingel, Ulrike
TI Pain beyond biology Response
SO PAIN
LA English
DT Letter
C1 [Colloca, Luana] NIMH, Natl Ctr Complementary & Alternat Med, Bethesda, MD 20892 USA.
[Colloca, Luana] NIH, Ctr Clin, Dept Bioeth, Bethesda, MD 20892 USA.
[Klinger, Regine] Univ Hamburg, Dept Psychol, Outpatient Clin Behav Therapy, Hamburg, Germany.
[Flor, Herta] Heidelberg Univ, Med Fac Mannheim, Cent Inst Mental Hlth, Dept Cognit & Clin Neurosci, Mannheim, Germany.
[Bingel, Ulrike] Univ Duisburg Essen, Univ Hosp Essen, Dept Neurol, Essen, Germany.
RP Colloca, L (reprint author), NIMH, Natl Ctr Complementary & Alternat Med, Bethesda, MD 20892 USA.
EM luana.colloca@nih.gov
NR 8
TC 0
Z9 0
U1 1
U2 18
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0304-3959
EI 1872-6623
J9 PAIN
JI Pain
PD NOV
PY 2013
VL 154
IS 11
BP 2572
EP 2572
DI 10.1016/j.pain.2013.06.048
PG 1
WC Anesthesiology; Clinical Neurology; Neurosciences
SC Anesthesiology; Neurosciences & Neurology
GA 238FG
UT WOS:000325927500044
PM 23973360
ER
PT J
AU Little, MP
AF Little, Mark P.
TI A review of non-cancer effects, especially circulatory and ocular
diseases
SO RADIATION AND ENVIRONMENTAL BIOPHYSICS
LA English
DT Review
DE Circulatory disease; Radiation; Heart disease; Stroke; Cataract; Central
nervous system; Review
ID ATOMIC-BOMB SURVIVORS; CORONARY-HEART-DISEASE; URANIUM MINERS COHORT;
RATE GAMMA-RADIATION; TERM-FOLLOW-UP; IONIZING-RADIATION;
CARDIOVASCULAR-DISEASES; CANCER INCIDENCE; DOSE-RESPONSE; MULTIMODEL
INFERENCE
AB There is a well-established association between high doses (> 5 Gy) of ionizing radiation exposure and damage to the heart and coronary arteries, although only recently have studies with high-quality individual dosimetry been conducted that would enable quantification of this risk adjusting for concomitant chemotherapy. The association between lower dose exposures and late occurring circulatory disease has only recently begun to emerge in the Japanese atomic bomb survivors and in various occupationally exposed cohorts and is still controversial. Excess relative risks per unit dose in moderate- and low-dose epidemiological studies are somewhat variable, possibly a result of confounding and effect modification by well-known (but unobserved) risk factors. Radiation doses of 1 Gy or more are associated with increased risk of posterior subcapsular cataract. Accumulating evidence from the Japanese atomic bomb survivors, Chernobyl liquidators, US astronauts, and various other exposed groups suggests that cortical cataracts may also be associated with ionizing radiation, although there is little evidence that nuclear cataracts are radiogenic. The dose-response appears to be linear, although modest thresholds (of no more than about 0.6 Gy) cannot be ruled out. A variety of other non-malignant effects have been observed after moderate/low-dose exposure in various groups, in particular respiratory and digestive disease and central nervous system (and in particular neuro-cognitive) damage. However, because these are generally only observed in isolated groups, or because the evidence is excessively heterogeneous, these associations must be treated with caution.
C1 NCI, Radiat Epidemiol Branch, Bethesda, MD 20892 USA.
RP Little, MP (reprint author), NCI, Radiat Epidemiol Branch, 9609 Med Ctr Dr MSC 9778, Bethesda, MD 20892 USA.
EM mark.little@nih.gov
FU Intramural Research Program of the National Institutes of Health, the
National Cancer Institute, Division of Cancer Epidemiology and Genetics
FX This work was supported by the Intramural Research Program of the
National Institutes of Health, the National Cancer Institute, Division
of Cancer Epidemiology and Genetics. The author is grateful for the
detailed and helpful comments of Dr Alice Sigurdson and the two
referees.
NR 108
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U2 25
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0301-634X
EI 1432-2099
J9 RADIAT ENVIRON BIOPH
JI Radiat. Environ. Biophys.
PD NOV
PY 2013
VL 52
IS 4
BP 435
EP 449
DI 10.1007/s00411-013-0484-7
PG 15
WC Biology; Biophysics; Environmental Sciences; Radiology, Nuclear Medicine
& Medical Imaging
SC Life Sciences & Biomedicine - Other Topics; Biophysics; Environmental
Sciences & Ecology; Radiology, Nuclear Medicine & Medical Imaging
GA 240DM
UT WOS:000326074900002
PM 23903347
ER
PT J
AU Gonzalez, RG
Furie, KL
Goldmacher, GV
Smith, WS
Kamalian, S
Payabvash, S
Harris, GJ
Halpern, EF
Koroshetz, WJ
Camargo, ECS
Dillon, WP
Lev, MH
AF Gonzalez, R. Gilberto
Furie, Karen L.
Goldmacher, Gregory V.
Smith, Wade S.
Kamalian, Shervin
Payabvash, Seyedmehdi
Harris, Gordon J.
Halpern, Elkan F.
Koroshetz, Walter J.
Camargo, Erica C. S.
Dillon, William P.
Lev, Michael H.
TI Good Outcome Rate of 35% in IV-tPA-Treated Patients With Computed
Tomography Angiography Confirmed Severe Anterior Circulation Occlusive
Stroke
SO STROKE
LA English
DT Article
DE computed tomography angiography; ischemic stroke; thrombolysis; tissue
plasminogen activator; treatment outcome
ID ACUTE ISCHEMIC-STROKE; TISSUE-PLASMINOGEN ACTIVATOR; ENDOVASCULAR
TREATMENT; TRIAL; ALTEPLASE; THERAPY; NINDS
AB Background and Purpose To determine the effect of intravenous tissue plasminogen activator (IV-tPA) on outcomes in patients with severe major anterior circulation ischemic stroke.
Methods Prospectively, 649 patients with acute stroke had admission National Institutes of Health stroke scale (NIHSS) scores, noncontrast computed tomography (CT), CT angiography (CTA), and 6-month outcome assessed using modified Rankin scale. IV-tPA treatment decisions were made before CTA, at the time of noncontrast CT scanning, as per routine clinical protocol. Severe symptoms were defined as NIHSS>10. Poor outcome was defined as modified Rankin scale >2. Major occlusions were identified on CTA. Univariate and multivariate stepwise-forward logistic regression analyses of the full cohort were performed.
Results Of 649 patients, 188 (29%) patients presented with NIHSS>10, and 64 out of 188 (34%) patients received IV-tPA. Admission NIHSS, large artery occlusion, and IV-tPA all independently predicted good outcomes; however, a significant interaction existed between IV-tPA and occlusion (P<0.001). Of the patients who presented with NIHSS>10 with anterior circulation occlusion, twice the percentage had good outcomes if they received IV-tPA (17 out of 49 patients, 35%) than if they did not (13 out of 77 patients, 17%; P=0.031). The number needed to treat was 7 (95% confidence interval, 3-60).
Conclusions IV-tPA treatment resulted in significantly better outcomes in patients with severely symptomatic stroke with major anterior circulation occlusions. The 35% good outcome rate was similar to rates found in endovascular therapy trials. Vascular imaging may help in patient selection and stratification for trials of IV-thrombolytic and endovascular therapies.
C1 [Gonzalez, R. Gilberto; Furie, Karen L.; Goldmacher, Gregory V.; Kamalian, Shervin; Payabvash, Seyedmehdi; Harris, Gordon J.; Halpern, Elkan F.; Camargo, Erica C. S.; Lev, Michael H.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Halpern, Elkan F.] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Halpern, Elkan F.] Massachusetts Gen Hosp, Inst Technol Assessment, Boston, MA 02114 USA.
Harvard Univ, Sch Med, Boston, MA USA.
[Goldmacher, Gregory V.] ICON Med Imaging Beacon Biosci, N Wales, PA USA.
[Smith, Wade S.] Univ Calif San Francisco, Dept Neurol, San Francisco, CA USA.
[Dillon, William P.] Univ Calif San Francisco, Dept Radiol, San Francisco, CA USA.
[Payabvash, Seyedmehdi] Univ Minnesota, Dept Radiol, Minneapolis, MN 55455 USA.
[Koroshetz, Walter J.] NINDS, Bethesda, MD 20892 USA.
[Camargo, Erica C. S.] Boston Univ, Med Ctr, Dept Neurol, Boston, MA 02215 USA.
[Furie, Karen L.] Rhode Isl Hosp, Dept Neurol, Providence, RI USA.
[Furie, Karen L.] Brown Univ, Warren Alpert Med Sch, Providence, RI 02912 USA.
RP Gonzalez, RG (reprint author), Massachusetts Gen Hosp, Dept Radiol, POB 9657, Boston, MA 02114 USA.
EM rggonzalez@partners.org
RI Demchuk, Andrew/E-1103-2012; Kamalian, Shervin/D-7667-2013
OI Demchuk, Andrew/0000-0002-4930-7789; Kamalian,
Shervin/0000-0001-8962-4773
FU National Institutes of Health Agency for Health Care Policy and Research
(AHCPR) [R01 HS11392-01A1]
FX This work was supported by the National Institutes of Health Agency for
Health Care Policy and Research (AHCPR), R01 HS11392-01A1. The funders
had no role in study design, data collection and analysis, decision to
publish, or preparation of the article.
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PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0039-2499
EI 1524-4628
J9 STROKE
JI Stroke
PD NOV
PY 2013
VL 44
IS 11
BP 3109
EP 3113
DI 10.1161/STROKEAHA.113.001938
PG 5
WC Clinical Neurology; Peripheral Vascular Disease
SC Neurosciences & Neurology; Cardiovascular System & Cardiology
GA 238YE
UT WOS:000325987300040
PM 24003051
ER
PT J
AU Goldenberg, RL
Farrow, V
McClure, EM
Reddy, UM
Fretts, RC
Schulkin, J
AF Goldenberg, Robert L.
Farrow, Victoria
McClure, Elizabeth M.
Reddy, Uma M.
Fretts, Ruth C.
Schulkin, Jay
TI Stillbirth: Knowledge and Practice among US Obstetrician-Gynecologists
SO AMERICAN JOURNAL OF PERINATOLOGY
LA English
DT Article
DE stillbirth; fetal death; obstetric practice; OBGYN knowledge
ID RISK-FACTORS; FETAL DEATH; INCOME COUNTRIES; UNITED-STATES; MORTALITY;
TRENDS; DISPARITIES; PREGNANCY; RATES; CARE
AB Objective To determine knowledge of U.S. obstetrician-gynecologists (OBGYNs) and individual and institutional practices regarding stillbirth. Study Design We surveyed 1,000 members of the American College of Obstetricians and Gynecologists regarding their knowledge of risk factors and causes of stillbirth and self-rated performance in stillbirth management. Results Of the 499 who responded, 365 currently practiced obstetrics. Knowledge regarding epidemiology, risk factors, and effective interventions to reduce stillbirth was only fair. About 30% of respondents were unaware that preeclampsia, advanced maternal age, elevated -fetoprotein, multiple gestation, cigarette smoking, illicit drug use, and being postterm increased risk. Tests to identify stillbirth causes were not performed consistently. Forty-two percent of respondents did not review test results to determine cause. Most hospitals did not have protocols for stillbirth evaluation nor preprinted forms to obtain appropriate stillbirth tests. Stillbirth audits with feedback were rarely performed. Conclusions OBGYN knowledge and institutional practice regarding stillbirth could be substantially improved. Residency programs need improved education regarding stillbirth. Hospitals and their OBGYN departments should focus more on stillbirth through continuing education programs and grand rounds and develop stillbirth management protocols and standardized order sheets to appropriately evaluate stillbirths. Audits that evaluate cause of death and preventability with a feedback loop focused on improvement in care should be considered.
C1 [Goldenberg, Robert L.] Columbia Univ, Dept Obstet & Gynecol, New York, NY USA.
[Farrow, Victoria; Schulkin, Jay] Amer Coll Obstetricians & Gynecologists, Washington, DC 20024 USA.
[Farrow, Victoria] American Univ, Dept Psychol, Washington, DC 20016 USA.
[McClure, Elizabeth M.] Res Triangle Inst, Durham, NC USA.
[Reddy, Uma M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Perinatol & Pregnancy Branch, Washington, DC USA.
[Fretts, Ruth C.] Massachusetts Gen Hosp, Dept Obstet & Gynecol, Boston, MA 02114 USA.
RP Goldenberg, RL (reprint author), Columbia Univ, Sch Med, Dept Obstet & Gynecol, 622 W 168th St,PH 16-66, New York, NY 10027 USA.
EM rlg88@columbia.edu
RI Guinan, Irazu/C-4498-2017
FU American College of Obstetricians and Gynecologists from the Maternal
and Child Health Bureau, Health Resources and Services Administration,
Department of Health and Human Services [UA6MC19010]; DOE
[DE-AC05-06OR23100]
FX This research was funded by cooperative agreement UA6MC19010 with the
American College of Obstetricians and Gynecologists from the Maternal
and Child Health Bureau, Health Resources and Services Administration,
Department of Health and Human Services. This research was performed
under an appointment to the Department of Homeland Security (DHS)
Scholarship and Fellowship Program, administered by the Oak Ridge
Institute for Science and Education (ORISE) through an interagency
agreement between the U.S. Department of Energy (DOE) and DHS. ORISE is
managed by Oak Ridge Associated Universities (ORAU) under DOE contract
number DE-AC05-06OR23100. All opinions expressed in this paper are the
authors' and do not necessarily reflect the policies and views of DHS,
DOE, or ORAU/ORISE.
NR 32
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PU THIEME MEDICAL PUBL INC
PI NEW YORK
PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA
SN 0735-1631
EI 1098-8785
J9 AM J PERINAT
JI Am. J. Perinatol.
PD NOV
PY 2013
VL 30
IS 10
BP 812
EP 820
DI 10.1055/s-0032-1333407
PG 8
WC Obstetrics & Gynecology; Pediatrics
SC Obstetrics & Gynecology; Pediatrics
GA 236LA
UT WOS:000325796700003
ER
PT J
AU Qian, WJ
Burke, TR
AF Qian, Wen-Jian
Burke, Terrence R., Jr.
TI Design and synthesis of a reagent for solid-phase incorporation of the
phosphothreonine mimetic (2S,3R)-2-amino-3-methyl-4-phosphonobutyric
acid (Pmab) into peptides in a bio-reversible
phosphonyl-bis-pivaloyloxymethyl (POM) prodrug form
SO AMINO ACIDS
LA English
DT Article
DE Phosphothreonine mimetic; Prodrug; Pmab; Solid-phase peptide synthesis;
Signal transduction
ID POLO-BOX DOMAIN; SIGNAL-TRANSDUCTION; SH2 DOMAIN; KINASE 1; POTENT;
PHOSPHOSERINE; PHOSPHATES; LIGANDS; TARGET; TOOLS
AB Reported herein are the synthesis and solid-phase peptide incorporation of N-Fmoc-(2S,3R)-2-amino-3-methyl-4-phosphonobutyric acid bis-pivaloyloxymethyl phosphoryl ester [Fmoc-Pmab(POM)(2)-OH, 2] as a phosphatase-stable phosphothreonine (pThr) mimetic bearing orthogonal protection suitable for the synthesis of Pmab-containing peptides having bio-reversible protection of the phosphonic acid moiety. This represents the first report of a bio-reversibly protected pThr mimetic in a form suitable for facile solid-phase peptide synthesis.
C1 [Qian, Wen-Jian; Burke, Terrence R., Jr.] NCI, Biol Chem Lab, Mol Discovery Program, Ctr Canc Res,Natl Canc Inst Frederick,NIH, Frederick, MD 21702 USA.
RP Burke, TR (reprint author), NCI, Biol Chem Lab, Mol Discovery Program, Ctr Canc Res,Natl Canc Inst Frederick,NIH, Frederick, MD 21702 USA.
EM burkete@helix.nih.gov
RI Burke, Terrence/N-2601-2014
FU NIH, Center for Cancer Research, NCI-Frederick; National Cancer
Institute, National Institutes of Health
FX This research was supported by the Intramural Research Program of the
NIH, Center for Cancer Research, NCI-Frederick and the National Cancer
Institute, National Institutes of Health.
NR 28
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U2 18
PU SPRINGER WIEN
PI WIEN
PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 WIEN, AUSTRIA
SN 0939-4451
EI 1438-2199
J9 AMINO ACIDS
JI Amino Acids
PD NOV
PY 2013
VL 45
IS 5
BP 1143
EP 1148
DI 10.1007/s00726-013-1567-0
PG 6
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 236QI
UT WOS:000325813800011
PM 23907438
ER
PT J
AU Lim, P
Dek, D
Try, V
Eastman, RT
Chy, S
Sreng, S
Suon, S
Mao, S
Sopha, C
Sam, B
Ashley, EA
Miotto, O
Dondorp, AM
White, NJ
Su, XZ
Char, MC
Anderson, JM
Amaratunga, C
Menard, D
Fairhurst, RM
AF Lim, Pharath
Dek, Dalin
Try, Vorleak
Eastman, Richard T.
Chy, Sophy
Sreng, Sokunthea
Suon, Seila
Mao, Sivanna
Sopha, Chantha
Sam, Baramey
Ashley, Elizabeth A.
Miotto, Olivo
Dondorp, Arjen M.
White, Nicholas J.
Su, Xin-zhuan
Char, Meng Chuor
Anderson, Jennifer M.
Amaratunga, Chanaki
Menard, Didier
Fairhurst, Rick M.
TI Ex Vivo Susceptibility of Plasmodium falciparum to Antimalarial Drugs in
Western, Northern, and Eastern Cambodia, 2011-2012: Association with
Molecular Markers
SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
LA English
DT Article
ID IN-VITRO; DIHYDROARTEMISININ-PIPERAQUINE; ARTEMETHER-LUMEFANTRINE;
ARTEMISININ RESISTANCE; MEFLOQUINE COMBINATION; CHLOROQUINE RESISTANCE;
CANDIDATE GENES; MALARIA; EFFICACY; ARTESUNATE
AB In 2008, dihydroartemisinin (DHA)-piperaquine (PPQ) became the first-line treatment for uncomplicated Plasmodium falciparum malaria in western Cambodia. Recent reports of increased treatment failure rates after DHA-PPQ therapy in this region suggest that parasite resistance to DHA, PPQ, or both is now adversely affecting treatment. While artemisinin (ART) resistance is established in western Cambodia, there is no evidence of PPQ resistance. To monitor for resistance to PPQ and other antimalarials, we measured drug susceptibilities for parasites collected in 2011 and 2012 from Pursat, Preah Vihear, and Ratanakiri, in western, northern, and eastern Cambodia, respectively. Using a SYBR green I fluorescence assay, we calculated the ex vivo 50% inhibitory concentrations (IC(50)s) of 310 parasites to six antimalarials: chloroquine (CQ), mefloquine (MQ), quinine (QN), PPQ, artesunate (ATS), and DHA. Geometric mean IC50s (GMIC(50)s) for all drugs (except PPQ) were significantly higher in Pursat and Preah Vihear than in Ratanakiri (P <= 0.001). An increased copy number of P. falciparum mdr1 (pfmdr1), an MQ resistance marker, was more prevalent in Pursat and Preah Vihear than in Ratanakiri and was associated with higher GMIC(50)s for MQ, QN, ATS, and DHA. An increased copy number of a chromosome 5 region (X5r), a candidate PPQ resistance marker, was detected in Pursat but was not associated with reduced susceptibility to PPQ. The ex vivo IC50 and pfmdr1 copy number are important tools in the surveillance of multidrug-resistant (MDR) parasites in Cambodia. While MDR P. falciparum is prevalent in western and northern Cambodia, there is no evidence for PPQ resistance, suggesting that DHA-PPQ treatment failures result mainly from ART resistance.
C1 [Lim, Pharath; Eastman, Richard T.; Su, Xin-zhuan; Anderson, Jennifer M.; Amaratunga, Chanaki; Fairhurst, Rick M.] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD USA.
[Lim, Pharath; Dek, Dalin; Try, Vorleak; Sreng, Sokunthea; Suon, Seila; Char, Meng Chuor] Natl Ctr Parasitol Entomol & Malaria Control, Phnom Penh, Cambodia.
[Lim, Pharath; Chy, Sophy; Menard, Didier] Inst Pasteur Cambodge, Phnom Penh, Cambodia.
[Mao, Sivanna] Sampov Meas Referral Hosp, Pursat, Cambodia.
[Sopha, Chantha] Makara 16 Referral Hosp, Preah Vihear, Cambodia.
[Sam, Baramey] Ratanakiri Referral Hosp, Ratanakiri, Cambodia.
[Ashley, Elizabeth A.; Miotto, Olivo; Dondorp, Arjen M.; White, Nicholas J.] Mahidol Univ, Fac Trop Med, Mahidol Oxford Trop Med Res Unit, Bangkok, Thailand.
[Ashley, Elizabeth A.; Dondorp, Arjen M.; White, Nicholas J.] Univ Oxford, Ctr Trop Med, Churchill Hosp, Oxford, England.
[Miotto, Olivo] Univ Oxford, MRC Ctr Genom & Global Hlth, Oxford, England.
RP Fairhurst, RM (reprint author), NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD USA.
EM rfairhurst@niaid.nih.gov
RI Menard, Didier/O-3294-2013;
OI Menard, Didier/0000-0003-1357-4495; Miotto, Olivo/0000-0001-8060-6771;
Su, Xinzhuan/0000-0003-3246-3248
FU Wellcome Trust; Wellcome Trust Mahidol University-Oxford Tropical
Medicine Research Programme; Intramural Research Program of the NIAID;
NIH; Department for International Development, United Kingdom; Tracking
Resistance Artemisinins Collaboration (TRAC)
FX A.A., O.M., A.M.D., and N.J.W. are supported by the Wellcome Trust as
part of the Wellcome Trust Mahidol University-Oxford Tropical Medicine
Research Programme. This study was funded by the Intramural Research
Program of the NIAID, NIH, and the Department for International
Development, United Kingdom, as part of the Tracking Resistance
Artemisinins Collaboration (TRAC).
NR 35
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Z9 13
U1 0
U2 9
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0066-4804
EI 1098-6596
J9 ANTIMICROB AGENTS CH
JI Antimicrob. Agents Chemother.
PD NOV
PY 2013
VL 57
IS 11
BP 5277
EP 5283
DI 10.1128/AAC.00687-13
PG 7
WC Microbiology; Pharmacology & Pharmacy
SC Microbiology; Pharmacology & Pharmacy
GA 235ZY
UT WOS:000325764000012
PM 23939897
ER
PT J
AU Havens, PL
Kiser, JJ
Stephensen, CB
Hazra, R
Flynn, PM
Wilson, CM
Rutledge, B
Bethel, J
Pan, CG
Woodhouse, LR
Van Loan, MD
Liu, N
Lujan-Zilbermann, J
Baker, A
Kapogiannis, BG
Gordon, CM
Mulligan, K
AF Havens, Peter L.
Kiser, Jennifer J.
Stephensen, Charles B.
Hazra, Rohan
Flynn, Patricia M.
Wilson, Craig M.
Rutledge, Brandy
Bethel, James
Pan, Cynthia G.
Woodhouse, Leslie R.
Van Loan, Marta D.
Liu, Nancy
Lujan-Zilbermann, Jorge
Baker, Alyne
Kapogiannis, Bill G.
Gordon, Catherine M.
Mulligan, Kathleen
CA Adolescent Med Trials Network HIV
TI Association of Higher Plasma Vitamin D Binding Protein and Lower Free
Calcitriol Levels with Tenofovir Disoproxil Fumarate Use and Plasma and
Intracellular Tenofovir Pharmacokinetics: Cause of a Functional Vitamin
D Deficiency?
SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
LA English
DT Article
ID HIV-INFECTED PATIENTS; OPTIMIZED BACKGROUND REGIMEN;
PARATHYROID-HORMONE; ANTIRETROVIRAL THERAPY; TUBULAR DYSFUNCTION;
ALKALINE-PHOSPHATASE; SALVAGE THERAPY; RENAL-FAILURE; CALCIUM; ADULTS
AB Tenofovir disoproxil fumarate (TDF) causes bone, endocrine, and renal changes by an unknown mechanism(s). Data are limited on tenofovir pharmacokinetics and these effects. Using baseline data from a multicenter study of HIV-infected youth on stable treatment with regimens containing TDF (n = 118) or lacking TDF (n = 85), we measured cross-sectional associations of TDF use with markers of renal function, vitamin D-calcium-parathyroid hormone balance, phosphate metabolism (tubular reabsorption of phosphate and fibroblast growth factor 23 [FGF23]), and bone turnover. Pharmacokinetic-pharmacodynamic associations with plasma tenofovir and intracellular tenofovir diphosphate concentrations were explored among those receiving TDF. The mean age was 20.9 (standard deviation [SD], 2.0) years; 63% were male; and 52% were African American. Compared to the no-TDF group, the TDF group showed lower mean estimated glomerular filtration rates and tubular reabsorption of phosphate, as well as higher parathyroid hormone and 1,25-dihydroxy vitamin D[1,25-OH(2) D] levels. The highest quintile of plasma tenofovir concentrations was associated with higher vitamin D binding protein, lower free 1,25-OH(2) D, higher 25-OH vitamin D, and higher serum calcium. The highest quintile of intracellular tenofovir diphosphate concentration was associated with lower FGF23. Higher plasma tenofovir concentrations were associated with higher vitamin D binding protein and lower free 1,25-OH(2) D, suggesting a functional vitamin D deficiency explaining TDF-associated increased parathyroid hormone. The finding of lower FGF23 accompanying higher intracellular tenofovir diphosphate suggests that different mechanisms mediate TDF-associated changes in phosphate handling. Separate pharmacokinetic properties may be associated with distinct TDF toxicities: tenofovir with parathyroid hormone and altered calcium balance and tenofovir diphosphate with hypophosphatemia and FGF23 regulation.
C1 [Havens, Peter L.; Pan, Cynthia G.] Med Coll Wisconsin, Childrens Hosp Wisconsin, Childrens Res Inst, Milwaukee, WI 53226 USA.
[Kiser, Jennifer J.] Univ Colorado, Skaggs Sch Pharm & Pharmaceut Sci, Dept Pharmaceut Sci, Aurora, CO USA.
[Stephensen, Charles B.; Woodhouse, Leslie R.; Van Loan, Marta D.] USDA ARS, Western Human Nutr Res Ctr, Davis, CA USA.
[Hazra, Rohan; Kapogiannis, Bill G.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
[Flynn, Patricia M.] St Jude Childrens Res Hosp, Memphis, TN 38105 USA.
[Wilson, Craig M.] Univ Alabama Birmingham, Birmingham, AL USA.
[Rutledge, Brandy; Bethel, James; Liu, Nancy] WESTAT Corp, Rockville, MD 20850 USA.
[Lujan-Zilbermann, Jorge] Univ S Florida, Coll Med, Tampa, FL USA.
[Baker, Alyne] Tulane Univ, New Orleans, LA 70118 USA.
[Gordon, Catherine M.] Hasbro Childrens Hosp, Providence, RI USA.
[Gordon, Catherine M.] Brown Univ, Providence, RI 02912 USA.
[Mulligan, Kathleen] Univ Calif San Francisco, San Francisco, CA 94143 USA.
RP Havens, PL (reprint author), Med Coll Wisconsin, Childrens Hosp Wisconsin, Childrens Res Inst, Milwaukee, WI 53226 USA.
EM phavens@mcw.edu; kathleen.mulligan@ucsf.edu
FU General Clinical Research Center Program of the National Center for
Research Resources; National Institutes of Health; Department of Health
and Human Services; Children's National Medical Center [M01RR020359];
University of Pennsylvania/Children's Hospital of Philadelphia
[NCRRUL1-RR-024134]; University of California at San Francisco
[UL1-RR024131]; Seattle Children's Hospital [UL1-RR025014]; Texas
Children's Hospital and Baylor College of Medicine [M01-RR00188]; Boston
University Medical Center [UL1-RR02517]; SUNY-Stony Brook [M01-RR10710];
Louisiana Board of Regents RC/EEP [RC/EEP-06]; Adolescent Trials Network
for HIV/AIDS Interventions (ATN) from the National Institutes of Health
through the Eunice Kennedy Shriver National Institute of Child Health
and Human Development [U01HD 040533, U01 HD 040474]; National Institutes
on Drug Abuse; Mental Health; National Institute of Allergy and
Infectious Diseases (NIAID); Eunice Kennedy Shriver National Institute
of Child Health and Human Development (NICHD); National Institute of
Mental Health (NIMH) [U01 A1068632]
FX Eight of these sites utilized their General Clinical Research Center
(GCRC)/Pediatric Clinical Research Center (PCRC) for the study; the
centers were supported by grants from the General Clinical Research
Center Program of the National Center for Research Resources, National
Institutes of Health, and Department of Health and Human Services under
the following grant numbers: Children's National Medical Center,
M01RR020359; University of Pennsylvania/Children's Hospital of
Philadelphia, NCRRUL1-RR-024134; University of California at San
Francisco, UL1-RR024131; Seattle Children's Hospital, UL1-RR025014;
Texas Children's Hospital and Baylor College of Medicine, M01-RR00188;
Boston University Medical Center, UL1-RR02517; and SUNY-Stony Brook,
M01-RR10710. The Tulane University Health Sciences Center utilized its
Clinical and Translational Research Center (CTRC) for the study; the
center was supported in whole or in part by funds provided through the
Louisiana Board of Regents RC/EEP (RC/EEP-06).; This work was supported
by the Adolescent Trials Network for HIV/AIDS Interventions (ATN) from
the National Institutes of Health (U01HD 040533 and U01 HD 040474]
through the Eunice Kennedy Shriver National Institute of Child Health
and Human Development [B. Kapogiannis]), with supplemental funding from
the National Institutes on Drug Abuse (N. Borek) and Mental Health (P.
Brouwers and S. Allison). The protocol was coendorsed by the
International Maternal Pediatric Adolescent AIDS Clinical Trials Group.
Support for the International Maternal Pediatric Adolescent AIDS
Clinical Trials Group (IMPAACT) was provided by the National Institute
of Allergy and Infectious Diseases (NIAID), the Eunice Kennedy Shriver
National Institute of Child Health and Human Development (NICHD), and
the National Institute of Mental Health (NIMH) (U01 A1068632). The study
was scientifically reviewed by the ATN's Therapeutic Leadership Group.
Network, scientific, and logistical support was provided by the ATN
Coordinating Center (C. Wilson and C. Partlow) at The University of
Alabama at Birmingham. Network operations and analytic support was
provided by the ATN Data and Operations Center at Westat, Inc. (J.
Korelitz and B. Driver).
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U2 8
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0066-4804
EI 1098-6596
J9 ANTIMICROB AGENTS CH
JI Antimicrob. Agents Chemother.
PD NOV
PY 2013
VL 57
IS 11
BP 5619
EP 5628
DI 10.1128/AAC.01096-13
PG 10
WC Microbiology; Pharmacology & Pharmacy
SC Microbiology; Pharmacology & Pharmacy
GA 235ZY
UT WOS:000325764000054
PM 24002093
ER
PT J
AU Natarajan, G
Shankaran, S
Laptook, AR
Pappas, A
Bann, CM
McDonald, SA
Das, A
Higgins, RD
Hintz, SR
Vohr, BR
AF Natarajan, Girija
Shankaran, Seetha
Laptook, Abbot R.
Pappas, Athina
Bann, Carla M.
McDonald, Scott A.
Das, Abhik
Higgins, Rosemary D.
Hintz, Susan R.
Vohr, Betty R.
CA Eunice Kennedy Shriver Natl Inst
TI Apgar scores at 10 min and outcomes at 6-7 years following
hypoxic-ischaemic encephalopathy
SO ARCHIVES OF DISEASE IN CHILDHOOD-FETAL AND NEONATAL EDITION
LA English
DT Article
DE Outcomes research; hypoxic-ischemic encephalopathy; apgar scores
ID EMERGENCY CARDIOVASCULAR CARE; WHOLE-BODY HYPOTHERMIA; CEREBRAL-PALSY;
CARDIOPULMONARY-RESUSCITATION; NEONATAL ENCEPHALOPATHY; THERAPEUTIC
HYPOTHERMIA; TERM INFANTS; ASSOCIATION; COMPLICATIONS; CHILDREN
AB Aim To determine the association between 10 min Apgar scores and 6-7-year outcomes in children with perinatal hypoxic-ischaemic encephalopathy (HIE) enrolled in the National Institute of Child Health and Human Development Neonatal Research Network (NICHD NRN) whole body cooling randomised controlled trial (RCT).
Methods Evaluations at 6-7years included the Wechsler Preschool and Primary Scale of Intelligence III or Wechsler Intelligence Scale for Children IV and Gross Motor Functional Classification Scale. Primary outcome was death/moderate or severe disability. Logistic regression was used to examine the association between 10 min Apgar scores and outcomes after adjusting for birth weight, gestational age, gender, outborn status, hypothermia treatment and centre.
Results In the study cohort (n=174), 64/85 (75%) of those with 10 min Apgar score of 0-3 had death/disability compared with 40/89 (45%) of those with scores >3. Each point increase in 10min Apgar scores was associated with a significantly lower adjusted risk of death/disability, death, death/IQ <70, death/cerebral palsy (CP) and disability, IQ<70 and CP among survivors (all p<0.05). Among the 24 children with a 10min Apgar score of 0, five (20.8%) survived without disability. The risk-adjusted probabilities of death/disability were significantly lower in cooled infants with Apgar scores of 0-3; there was no significant interaction between cooling and Apgar scores (p=0.26).
Conclusions Among children with perinatal HIE enrolled in the NICHD cooling RCT, 10 min Apgar scores were significantly associated with school-age outcomes. A fifth of infants with 10 min Apgar score of 0 survived without disability to school age, suggesting the need for caution in limiting resuscitation to a specified duration.
C1 [Natarajan, Girija; Shankaran, Seetha; Pappas, Athina] Wayne State Univ, Dept Pediat, Detroit, MI 48202 USA.
[Laptook, Abbot R.; Vohr, Betty R.] Brown Univ, Women & Infants Hosp, Dept Pediat, Providence, RI 02908 USA.
[Bann, Carla M.; McDonald, Scott A.] RTI Int, Social Stat & Environm Sci Unit, Res Triangle Pk, NC USA.
[Das, Abhik] Social Stat & Environm Sci Unit, Rockville, MD USA.
[Higgins, Rosemary D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
[Hintz, Susan R.] Stanford Univ, Sch Med, Dept Pediat, Palo Alto, CA 94304 USA.
RP Natarajan, G (reprint author), Childrens Hosp Michigan, Div Neonatol, Dept Pediat, 3901 Beaubien Blvd, Detroit, MI 48201 USA.
EM gnatara@med.wayne.edu
FU National Institutes of Health; Eunice Kennedy Shriver National Institute
of Child Health and Human Development (NICHD)
FX The Neonatal Research Network's Whole-Body Hypothermia Trial and its 6-7
Year School-age Follow-up were provided grant support by the National
Institutes of Health and the Eunice Kennedy Shriver National Institute
of Child Health and Human Development (NICHD). Grant numbers are
provided for each site above. Data collected at participating sites of
the NICHD Neonatal Research Network (NRN) were transmitted to RTI
International, the data coordinating centre (DCC) for the network, which
stored, managed and analysed the data for this study. On behalf of the
NRN, Dr Abhik Das (DCC Principal Investigator) and Mr Scott A. McDonald
(DCC Statistician) had full access to all the data in the study and take
responsibility for the integrity of the data and accuracy of the data
analysis.
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U1 0
U2 7
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 1359-2998
EI 1468-2052
J9 ARCH DIS CHILD-FETAL
JI Arch. Dis. Child.-Fetal Neonatal Ed.
PD NOV
PY 2013
VL 98
IS 6
BP F473
EP F479
DI 10.1136/archdischild-2013-303692
PG 7
WC Pediatrics
SC Pediatrics
GA 233GN
UT WOS:000325556000003
PM 23896791
ER
PT J
AU Fang, ZZ
Krausz, KW
Tanaka, N
Li, F
Qu, AJ
Idle, JR
Gonzalez, FJ
AF Fang, Zhong-Ze
Krausz, Kristopher W.
Tanaka, Naoki
Li, Fei
Qu, Aijuan
Idle, Jeffrey R.
Gonzalez, Frank J.
TI Metabolomics reveals trichloroacetate as a major contributor to
trichloroethylene-induced metabolic alterations in mouse urine and serum
SO ARCHIVES OF TOXICOLOGY
LA English
DT Article
DE Trichloroethylene; Dichloroacetate; Trichloroacetate; PPAR alpha;
Metabolomics; Toxicity
ID ACTIVATED-RECEPTOR-ALPHA; LIVER-TUMOR-INDUCTION; BILE-ACID HOMEOSTASIS;
PPAR-ALPHA; PROTEOMIC ANALYSIS; HEPATOCELLULAR-CARCINOMA; B6C3F1 MICE;
WILD-TYPE; DICHLOROACETATE; SPECTROMETRY
AB Trichloroethylene (TCE)-induced liver toxicity and carcinogenesis is believed to be mediated in part by activation of the peroxisome proliferator-activated receptor alpha (PPAR alpha). However, the contribution of the two TCE metabolites, dichloroacetate (DCA) and trichloroacetate (TCA) to the toxicity of TCE, remains unclear. The aim of the present study was to determine the metabolite profiles in serum and urine upon exposure of mice to TCE, to aid in determining the metabolic response to TCE exposure and the contribution of DCA and TCA to TCE toxicity. C57BL/6 mice were administered TCE, TCA, or DCA, and urine and serum subjected to ultra-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry (UPLC-ESI-QTOFMS)-based global metabolomics analysis. The ions were identified through searching metabolomics databases and by comparison with authentic standards, and quantitated using multiple reactions monitoring. Quantitative polymerase chain reaction of mRNA, biochemical analysis, and liver histology were also performed. TCE exposure resulted in a decrease in urine of metabolites involved in fatty acid metabolism, resulting from altered expression of PPAR alpha target genes. TCE treatment also induced altered phospholipid homeostasis in serum, as revealed by increased serum lysophosphatidylcholine 18:0 and 18:1, and phosphatidylcholine metabolites. TCA administration revealed similar metabolite profiles in urine and serum upon TCE exposure, which correlated with a more robust induction of PPAR alpha target gene expression associated with TCA than DCA treatment. These data show the metabolic response to TCE exposure and demonstrate that TCA is the major contributor to TCE-induced metabolite alterations observed in urine and serum.
C1 [Fang, Zhong-Ze; Krausz, Kristopher W.; Tanaka, Naoki; Li, Fei; Qu, Aijuan; Idle, Jeffrey R.; Gonzalez, Frank J.] NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Gonzalez, FJ (reprint author), NCI, Lab Metab, Ctr Canc Res, NIH, Bldg 37,Room 3106, Bethesda, MD 20892 USA.
EM gonzalef@mail.nih.gov
RI Li, Fei/F-6849-2013;
OI Idle, Jeff/0000-0002-6143-1520
FU Intramural Research Program of the Center for Cancer Research, National
Cancer Institute, National Institutes of Health
FX This work was supported in part by the Intramural Research Program of
the Center for Cancer Research, National Cancer Institute, National
Institutes of Health.
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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 2013
VL 87
IS 11
BP 1975
EP 1987
DI 10.1007/s00204-013-1053-1
PG 13
WC Toxicology
SC Toxicology
GA 235EW
UT WOS:000325700300008
PM 23575800
ER
PT J
AU Reis, JP
Launer, LJ
Terry, JG
Loria, CM
Al Hazzouri, AZ
Sidney, S
Yaffe, K
Jacobs, DR
Whitlow, CT
Zhu, N
Carr, JJ
AF Reis, Jared P.
Launer, Lenore J.
Terry, James G.
Loria, Catherine M.
Al Hazzouri, Adina Zeki
Sidney, Stephen
Yaffe, Kristine
Jacobs, David R., Jr.
Whitlow, Christopher T.
Zhu, Na
Carr, J. Jeffrey
TI Subclinical atherosclerotic calcification and cognitive functioning in
middle-aged adults: The CARDIA study
SO ATHEROSCLEROSIS
LA English
DT Article
DE Atherosclerosis; Cognition; Subclinical disease; Risk factors
ID CORONARY-ARTERY CALCIUM; DIABETES-MELLITUS; BLOOD-PRESSURE; DEMENTIA;
ASSOCIATION; IMPAIRMENT; MIDLIFE; HEALTH; RISK
AB Objective: Cardiovascular risk factors in middle-age are associated with cognitive impairment and dementia in older age. Less is known about the burden of calcified subclinical atherosclerosis and cognition, especially in midlife. We examined the association of coronary artery and abdominal aortic calcified plaque (CAC and AAC, respectively) with cognitive functioning in middle-aged adults.
Methods: This cross-sectional study included 2510 black and white adults (age: 43-55 years) without heart disease or stroke who completed a year 25 follow-up exam (2010-11) as part of the Coronary Artery Risk Development in Young Adults Study. CAC and AAC were measured with non-contrast computed tomography. Cognition was assessed with the Digit Symbol Substitution Test (DSST) (psychomotor speed), Stroop Test (executive function), and Rey Auditory Verbal Learning Test (RAVLT) (verbal memory).
Results: A greater amount of CAC and AAC was associated with worse performance on each test of cognitive function after adjustment for age, sex, race, education, and study center. Associations were attenuated, but remained significant for the DSST and RAVLT following additional adjustment for vascular risk factors, including adiposity, smoking, alcohol use, dyslipidemia, hypertension, and diabetes. Compared to participants without CAC or AAC, those with both CAC and AAC, but not CAC or AAC alone was associated with lower DSST scores (p < 0.05).
Conclusions: In this community-based sample, greater subclinical atherosclerotic calcification was associated with worse psychomotor speed and memory in midlife. These findings underscore the importance of a life course approach to the study of cognitive impairment with aging. Published by Elsevier Ireland Ltd.
C1 [Reis, Jared P.; Loria, Catherine M.] NHLBI, Div Cardiovasc Sci, Bethesda, MD 20892 USA.
[Launer, Lenore J.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
[Terry, James G.; Whitlow, Christopher T.; Carr, J. Jeffrey] Wake Forest Univ, Bowman Gray Sch Med, Dept Radiol, Winston Salem, NC USA.
[Al Hazzouri, Adina Zeki; Yaffe, Kristine] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Yaffe, Kristine] San Francisco VA Med Ctr, San Francisco, CA USA.
[Sidney, Stephen] Kaiser Permanente No Calif, Div Res, Oakland, CA USA.
[Jacobs, David R., Jr.; Zhu, Na] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA.
[Jacobs, David R., Jr.] Univ Oslo, Dept Nutr, Oslo, Norway.
RP Reis, JP (reprint author), NHLBI, Div Cardiovasc Sci, 6701 Rockledge Dr,Suite 10197, Bethesda, MD 20892 USA.
EM reisjp@mail.nih.gov
RI Carr, John/A-1938-2012
OI Carr, John/0000-0002-4398-8237
FU National Heart, Lung, and Blood Institute [N01-HC95095, N01-HC48047,
N01-HC48050, N01-HC48049, N01-HC48048, R01-HL098445]
FX The Coronary Risk Development in Young Adults Study is conducted and
supported by the National Heart, Lung, and Blood Institute (N01-HC95095,
N01-HC48047, N01-HC48050, N01-HC48049, N01-HC48048, R01-HL098445).
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U1 1
U2 10
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 2013
VL 231
IS 1
BP 72
EP 77
DI 10.1016/j.atherosclerosis.2013.08.038
PG 6
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 235XH
UT WOS:000325755300014
PM 24125414
ER
PT J
AU Xia, D
Esser, L
Tang, WK
Zhou, F
Zhou, YH
Yu, LD
Yu, CA
AF Xia, Di
Esser, Lothar
Tang, Wai-Kwan
Zhou, Fei
Zhou, Yihui
Yu, Linda
Yu, Chang-An
TI Structural analysis of cytochrome bc(1) complexes: Implications to the
mechanism of function
SO BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS
LA English
DT Review
DE Cytochrome bc(1) complex; Bifurcated electron flow; Mechanism of
ubiquinol oxidation; Crystal structure; Control of ISP domain movement
ID IRON-SULFUR PROTEIN; YEAST SACCHAROMYCES-CEREVISIAE; QUINOL OXIDATION
SITE; MITOCHONDRIAL PROCESSING PEPTIDASE; BACTERIUM
RHODOBACTER-SPHAEROIDES; ELECTRON-TRANSFER REACTIONS; BOVINE
HEART-MITOCHONDRIA; WATER-SOLUBLE FRAGMENT; X-RAY-STRUCTURE; C REDUCTASE
AB The cytochrome bc(1) complex (bc(1)) is the mid-segment of the cellular respiratory chain of mitochondria and many aerobic prokaryotic organisms: it is also part of the photosynthetic apparatus of non-oxygenic purple bacteria. The bc(1) complex catalyzes the reaction of transferring electrons from the low potential substrate ubiquinol to high potential cytochrome c. Concomitantly, bc(1) translocates protons across the membrane, contributing to the proton-motive force essential for a variety of cellular activities such as ATP synthesis. Structural investigations of bc(1) have been exceedingly successful, yielding atomic resolution structures of bc(1) from various organisms and trapped in different reaction intermediates. These structures have confirmed and unified results of decades of experiments and have contributed to our understanding of the mechanism of bc(1) functions as well as its inactivation by respiratory inhibitors. This article is part of a Special Issue entitled: Respiratory complex III and related bc complexes. Published by Elsevier B.V.
C1 [Xia, Di; Esser, Lothar; Tang, Wai-Kwan; Zhou, Fei; Zhou, Yihui] NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Yu, Linda; Yu, Chang-An] Oklahoma State Univ, Dept Biochem & Mol Biol, Stillwater, OK 74078 USA.
RP Xia, D (reprint author), 37 Convent Dr Bldg 37,Room 2122C, Bethesda, MD 20892 USA.
EM xiad@mail.nih.gov
FU NIH, National Cancer Institute, Center for Cancer Research; NIH [GM
30721]
FX We thank George Leiman for editorial assistance during the preparation
of this manuscript This research was supported in part by the Intramural
Research Program of the NIH, National Cancer Institute, Center for
Cancer Research, and in part from an NIH grant (GM 30721) to CAY.
NR 112
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U1 2
U2 41
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0005-2728
EI 0006-3002
J9 BBA-BIOENERGETICS
JI Biochim. Biophys. Acta-Bioenerg.
PD NOV-DEC
PY 2013
VL 1827
IS 11-12
SI SI
BP 1278
EP 1294
DI 10.1016/j.bbabio.2012.11.008
PG 17
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 232RA
UT WOS:000325510500003
PM 23201476
ER
PT J
AU Dibrova, DV
Cherepanov, DA
Galperin, MY
Skulachev, VP
Mulkidjanian, AY
AF Dibrova, Daria V.
Cherepanov, Dmitry A.
Galperin, Michael Y.
Skulachev, Vladimir P.
Mulkidjanian, Armen Y.
TI Evolution of cytochrome bc complexes: From membrane-anchored
dehydrogenases of ancient bacteria to triggers of apoptosis in
vertebrates
SO BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS
LA English
DT Review
DE Bioenergetics, molecular evolution, ubiquinol: cytochrome c
oxidoreductase; ubiquinone; plastoquinone; cytochrome c; cardiolipin,
cell death, photosynthesis, apoptosome
ID TARGETED PLASTOQUINONE DERIVATIVES; PURPLE PHOTOSYNTHETIC BACTERIA;
TRANSMEMBRANE PROTON-TRANSFER; INNER MITOCHONDRIAL-MEMBRANE; ANAEROBIC
AMMONIUM OXIDATION; UNIVERSAL COMMON ANCESTOR; OXYGEN SPECIES
GENERATION; IRON-SULFUR PROTEIN; ACTIVATED Q-CYCLE; X-RAY-STRUCTURE
AB This review traces the evolution of the cytochrome bc complexes from their early spread among prokaryotic lineages and up to the mitochondrial cytochrome bc(1) complex (complex III) and its role in apoptosis. The results of phylogenomic analysis suggest that the bacterial cytochrome b(6)f-type complexes with short cytochromes b were the ancient form that preceded in evolution the cytochrome bc(1)-type complexes with long cytochromes b. The common ancestor of the b(6)f-type and the bc(1)-type complexes probably resembled the b(6)f-type complexes found in Heliobacteriaceae and in some Planctomycetes. Lateral transfers of cytochrome bc operons could account for the several instances of acquisition of different types of bacterial cytochrome bc complexes by archaea. The gradual oxygenation of the atmosphere could be the key evolutionary factor that has driven further divergence and spread of the cytochrome bc complexes. On the one hand, oxygen could be used as a very efficient terminal electron acceptor. On the other hand, auto-oxidation of the components of the bc complex results in the generation of reactive oxygen species (ROS), which necessitated diverse adaptations of the b(6)f-type and bc(1)-type complexes, as well as other, functionally coupled proteins. A detailed scenario of the gradual involvement of the cardiolipin-containing mitochondrial cytochrome bc(1) complex into the intrinsic apoptotic pathway is proposed, where the functioning of the complex as an apoptotic trigger is viewed as a way to accelerate the elimination of the cells with irreparably damaged, ROS-producing mitochondria. This article is part of a Special Issue entitled: Respiratory complex III and related bc complexes. (C) 2013 Elsevier B.V. All rights reserved.
C1 [Dibrova, Daria V.; Mulkidjanian, Armen Y.] Univ Osnabruck, Sch Phys, D-49069 Osnabruck, Germany.
[Dibrova, Daria V.; Skulachev, Vladimir P.; Mulkidjanian, Armen Y.] Moscow MV Lomonosov State Univ, Sch Bioengn & Bioinformat, Moscow 119992, Russia.
[Dibrova, Daria V.] Moscow MV Lomonosov State Univ, Inst Mitoengn, Moscow 119992, Russia.
[Cherepanov, Dmitry A.] RAS, AN Frumkin Electrochem Inst, Moscow 119991, Russia.
[Galperin, Michael Y.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
[Skulachev, Vladimir P.; Mulkidjanian, Armen Y.] Moscow MV Lomonosov State Univ, AN Belozersky Inst Physicochem Biol, Moscow 119991, Russia.
RP Mulkidjanian, AY (reprint author), Univ Osnabruck, Sch Phys, D-49069 Osnabruck, Germany.
EM amulkid@uos.de
RI Mulkidjanian, Armen/J-8086-2013; Cherepanov, Dmitry/R-8391-2016;
OI Mulkidjanian, Armen/0000-0001-5844-3064; Galperin,
Michael/0000-0002-2265-5572
FU Deutsche Forschungsgemeinschaft [DFG-Mu-1285/1-10, DFG-436-RUS
113/963/0-1]; COST Action of the EU [CM0902]; Russian Government
[02.740.11.5228]; Deutscher Akademischer Austausch Dienst; Russian
Foundation for Basic Research [RFBR 0-04-91331]; Intramural Research
Program of the NIH at the National Library of Medicine
FX Very useful discussions with Drs. D. Frishman, E.V. Koonin, K.S.
Makarova and Y.I. Wolf are greatly appreciated. Of a particularly value
for us was the suggestion of Dr. A.V. Bogachev on the emergence of first
high-potential electron acceptors in the framework of biogenic
photosynthesis. We are grateful to an anonymous Reviewer for pointing
out the binding of the cn heme in the b6f-type
complexes by the CXGG motif. This study was supported by the
Mitoengineering Institute, Moscow, Russia and grants from the Deutsche
Forschungsgemeinschaft (DFG-Mu-1285/1-10, DFG-436-RUS 113/963/0-1), the
COST Action CM0902 of the EU and the Russian Government (
02.740.11.5228) to A.Y.M., from the Deutscher Akademischer Austausch
Dienst to D.V.D. and from the Russian Foundation for Basic Research
(RFBR 0-04-91331) to V.P.S. M.Y.G is supported by the Intramural
Research Program of the NIH at the National Library of Medicine.
NR 238
TC 33
Z9 34
U1 3
U2 44
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0005-2728
EI 0006-3002
J9 BBA-BIOENERGETICS
JI Biochim. Biophys. Acta-Bioenerg.
PD NOV-DEC
PY 2013
VL 1827
IS 11-12
SI SI
BP 1407
EP 1427
DI 10.1016/j.bbabio.2013.07.006
PG 21
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 232RA
UT WOS:000325510500014
PM 23871937
ER
PT J
AU Suarez, C
Welsch, S
Chlanda, P
Hagen, W
Hoppe, S
Kolovou, A
Pagnier, I
Raoult, D
Locker, JK
AF Suarez, Cristina
Welsch, Sonja
Chlanda, Petr
Hagen, Wim
Hoppe, Simone
Kolovou, Androniki
Pagnier, Isabelle
Raoult, Didier
Locker, Jacomine Krijnse
TI Open membranes are the precursors for assembly of large DNA viruses
SO CELLULAR MICROBIOLOGY
LA English
DT Article
ID VACCINIA VIRUS; INTERMEDIATE COMPARTMENT; ENDOPLASMIC-RETICULUM; GIANT
MIMIVIRUS; NONENVELOPED VIRUSES; MELTING-POT; AMEBAS; MICROORGANISMS;
MORPHOGENESIS; PENETRATION
AB Nucleo cytoplasmic large DNA viruses (NCLDVs) are a group of double-stranded DNA viruses that replicate their DNA partly or entirely in the cytoplasm in association with viral factories (VFs). They share about 50 genes suggesting that they are derived from a common ancestor. Using transmission electron microscopy (TEM) and electron tomography (ET) we showed that the NCLDV vaccinia virus (VACV) acquires its membrane from open membrane intermediates, derived from the ER. These open membranes contribute to the formation of a single open membrane of the immature virion, shaped into a sphere by the assembly of the viral scaffold protein on its convex side. We now compare VACV with the NCLDV Mimivirus by TEM and ET and show that the latter also acquires its membrane from open membrane intermediates that accumulate at the periphery of the cytoplasmic VF. In analogy to VACV this membrane is shaped by the assembly of a layer on the convexside of its membrane, likely representing the Mimivirus capsid protein. By quantitative ET we show for both viruses that the open membrane intermediates of assembly adopt an open-eight' conformation with a characteristic diameter of 90nm for Mimi- and 50nm for VACV. We discuss these results with respect to the common ancestry of NCLDVs and propose a hypothesis on the possible origin of this unusual membrane biogenesis.
C1 [Suarez, Cristina; Hoppe, Simone; Kolovou, Androniki; Locker, Jacomine Krijnse] Heidelberg Univ, Electron Microscopy Core Facil, D-69120 Heidelberg, Germany.
[Suarez, Cristina; Hoppe, Simone; Kolovou, Androniki; Locker, Jacomine Krijnse] Heidelberg Univ, Dept Infect Dis, D-69120 Heidelberg, Germany.
[Welsch, Sonja; Hagen, Wim] European Mol Biol Lab, Struct & Computat Biol Program, D-69120 Heidelberg, Germany.
[Chlanda, Petr] NICHHD, NIH, Bethesda, MD 20892 USA.
[Pagnier, Isabelle; Raoult, Didier] Aix Marseille Univ, URMITE, UMR CNRS 7278, IRD 198,INSERM 1095,Fac Med, Marseille, France.
RP Locker, JK (reprint author), Heidelberg Univ, Electron Microscopy Core Facil, Neuenheimer Feld 267, D-69120 Heidelberg, Germany.
EM jacomine.krijnse@bioquant.uni-heidelberg.de
OI Pagnier, Isabelle/0000-0002-1724-3450
FU priority programme SPP1175 of the German scientific research foundation
(DFG); cluster of excellence CellNetworks
FX This work was funded by the priority programme SPP1175 of the German
scientific research foundation (DFG). We also thank the electron
microscopy core facility of the Heidelberg university and their staff
for technical as well as the cluster of excellence CellNetworks for
financial support.
NR 40
TC 13
Z9 13
U1 0
U2 8
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1462-5814
EI 1462-5822
J9 CELL MICROBIOL
JI Cell Microbiol.
PD NOV
PY 2013
VL 15
IS 11
BP 1883
EP 1895
DI 10.1111/cmi.12156
PG 13
WC Cell Biology; Microbiology
SC Cell Biology; Microbiology
GA 233CD
UT WOS:000325541700008
PM 23751082
ER
PT J
AU Inouchi, M
Matsumoto, R
Taki, J
Kikuchi, T
Mitsueda-Ono, T
Mikuni, N
Wheaton, L
Hallett, M
Fukuyama, H
Shibasaki, H
Takahashi, R
Ikeda, A
AF Inouchi, Morito
Matsumoto, Riki
Taki, Junya
Kikuchi, Takayuki
Mitsueda-Ono, Takahiro
Mikuni, Nobuhiro
Wheaton, Lewis
Hallett, Mark
Fukuyama, Hidenao
Shibasaki, Hiroshi
Takahashi, Ryosuke
Ikeda, Akio
TI Role of posterior parietal cortex in reaching movements in humans:
Clinical implication for 'optic ataxia'
SO CLINICAL NEUROPHYSIOLOGY
LA English
DT Article
DE Bereitschaftspotential; Cortical electrical stimulation; Optic ataxia;
Posterior parietal cortex; Reaching
ID TRANSCRANIAL MAGNETIC STIMULATION; POSITRON-EMISSION-TOMOGRAPHY;
SUPPLEMENTARY MOTOR AREA; FUNCTIONAL-ANATOMY; FRONTAL-CORTEX; HUMAN
BRAIN; PARIETOOCCIPITAL CORTEX; EFFECTOR INFORMATION; VOLUNTARY
MOVEMENTS; ONLINE ADJUSTMENTS
AB Objective: To clarify the spatio-temporal profile of cortical activity related to reaching movement in the posterior parietal cortex (PPC) in humans.
Methods: Four patients with intractable partial epilepsy who underwent subdural electrode implantation were studied as a part of pre-surgical evaluation. We investigated the Bereitschaftspotential (BP) associated with reaching and correlated the findings with the effect of electrical stimulation of the same cortical area.
Results: BPs specific for reaching, as compared with BPs for simple movements by the hand or arm contralateral to the implanted hemisphere, were recognized in all patients, mainly around the intraparietal sulcus (IPS), the superior parietal lobule (SPL) and the precuneus. BPs near the IPS had the earlier onset than BPs in the SPL. Electrical stimulation of a part of the PPC, where the reach-specific BPs were recorded, selectively impaired reaching.
Conclusions: Intracranial BP recording and cortical electrical stimulation delineated human reach-related areas in the PPC. Significance: The present study for the first time by direct cortical recording in humans demonstrates that parts of the cortices around the IPS and SPL play a crucial role in visually-guided reaching. (C) 2013 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.
C1 [Inouchi, Morito; Matsumoto, Riki; Mitsueda-Ono, Takahiro; Shibasaki, Hiroshi; Takahashi, Ryosuke; Ikeda, Akio] Kyoto Univ, Grad Sch Med, Dept Neurol, Kyoto 6068507, Japan.
[Taki, Junya; Kikuchi, Takayuki; Mikuni, Nobuhiro] Kyoto Univ, Grad Sch Med, Dept Neurosurg, Kyoto 6068507, Japan.
[Fukuyama, Hidenao] Kyoto Univ, Grad Sch Med, Human Brain Res Ctr, Kyoto 6068507, Japan.
[Taki, Junya] Tenri Hosp, Dept Neurosurg, Tenri, Nara 632, Japan.
[Mitsueda-Ono, Takahiro] Otsu Red Cross Hosp, Dept Neurol, Otsu, Shiga, Japan.
[Mikuni, Nobuhiro] Sapporo Med Univ, Dept Neurosurg, Sapporo, Hokkaido, Japan.
[Wheaton, Lewis] Georgia Inst Technol, Sch Appl Physiol, Atlanta, GA 30332 USA.
[Hallett, Mark] NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA.
RP Ikeda, A (reprint author), Kyoto Univ, Grad Sch Med, Dept Neurol, Sakyo Ku, 54 Shogoin Kawaharacho, Kyoto 6068507, Japan.
EM akio@kuhp.kyoto-u.ac.jp
RI Matsumoto, Riki/I-8397-2016;
OI Matsumoto, Riki/0000-0003-3985-9210; Ikeda, Akio/0000-0002-0790-2598;
Wheaton, Lewis/0000-0003-0771-0294
FU Research Grant for Nervous and Mental Disorders from the Ministry of
Health and Welfare [22A-6]; Research Grant from the Japan Epilepsy
Research Foundation
FX This work was supported by The Research Grant for Nervous and Mental
Disorders (22A-6) from the Ministry of Health and Welfare, The Research
Grant from the Japan Epilepsy Research Foundation (2009-2010) and
Grants-in-Aid for Scientific Research
NR 79
TC 3
Z9 3
U1 3
U2 13
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 1388-2457
EI 1872-8952
J9 CLIN NEUROPHYSIOL
JI Clin. Neurophysiol.
PD NOV
PY 2013
VL 124
IS 11
BP 2230
EP 2241
DI 10.1016/j.clinph.2013.05.011
PG 12
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 236FE
UT WOS:000325779800021
PM 23831168
ER
PT J
AU Berger, VW
AF Berger, Vance W.
TI CORR Insights(A (R)): Have Levels of Evidence Improved the Quality of
Orthopaedic Research?
SO CLINICAL ORTHOPAEDICS AND RELATED RESEARCH
LA English
DT Editorial Material
ID RANDOMIZED CLINICAL-TRIALS; SELECTION
C1 NCI, Canc Prevent Div, Rockville, MD 20850 USA.
RP Berger, VW (reprint author), NCI, Canc Prevent Div, 9609 Med Ctr Dr, Rockville, MD 20850 USA.
EM vb78c@nih.gov
NR 8
TC 1
Z9 1
U1 0
U2 2
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0009-921X
EI 1528-1132
J9 CLIN ORTHOP RELAT R
JI Clin. Orthop. Rel. Res.
PD NOV
PY 2013
VL 471
IS 11
BP 3687
EP 3688
DI 10.1007/s11999-013-3203-4
PG 2
WC Orthopedics; Surgery
SC Orthopedics; Surgery
GA 231ND
UT WOS:000325422700045
PM 23904248
ER
PT J
AU Osman, J
Galli, S
Hanafy, M
Tang, X
Ahmed, A
AF Osman, J.
Galli, S.
Hanafy, M.
Tang, X.
Ahmed, A.
TI Identification of novel biomarkers in neuroblastoma associated with the
risk for bone marrow metastasis: a pilot study
SO CLINICAL & TRANSLATIONAL ONCOLOGY
LA English
DT Article
DE Neuroblastoma; Nestin; XIAP; VEGF; Immunohistochemistry
ID ENDOTHELIAL GROWTH-FACTOR; ANGIOGENIC FACTORS; NESTIN EXPRESSION;
GENE-EXPRESSION; CELLS; TUMORS; PROGRESSION; INHIBITOR; APOPTOSIS;
PATHWAYS
AB Neuroblastoma is a common pediatric neoplasm with variable histopathological features that carry an inherent risk of developing distant metastases, in particular bone marrow metastasis. Nestin, X-linked inhibitor of apoptosis (XIAP) and vascular growth factors (VEGF) are biomarkers that are implicated in the tumorigenesis of various cancers. We studied the expression of these biomarkers in neuroblastoma, in relation to bone marrow (BM) metastasis and other histologic parameters.
Patients with neuroblastoma included seven with BM metastasis and 12 with non-metastatic tumors. Slides from the primary tumors were immunostained with antibodies against nestin, XIAP, VEGF-A, VEGF-B, VEGF-D, VEGF-R1, and VEGF-R2. Immunostaining results were evaluated by two pathologists, graded and statistically correlated with the risk of developing BM metastasis.
Nestin was expressed in 16/19 cases with no significant difference between patients with BM metastasis and those without BM metastasis. XIAP was identified in 18/19 tumor cases; the staining density was significantly lower in patients with bone marrow metastasis and those with unfavorable histology. VEGF-R1, VEGF-R2, and VEGF-B were expressed while VEGF-A and VEGF-D were not. Significantly, higher expression of VEGF-B was noted in patients with BM metastasis.
Expression of VEGF-B and XIAP in neuroblastoma may play a role in the development of bone marrow metastasis. Given the limited number of patients in this study, a larger cohort is needed to validate these findings.
C1 [Osman, J.; Hanafy, M.; Tang, X.] Arkansas Childrens Hosp, Dept Pathol, Little Rock, AR 72202 USA.
[Galli, S.] NCI, NIH, Bethesda, MD 20892 USA.
[Ahmed, A.] Childrens Mercy Hosp & Clin, Kansas City, MO 64108 USA.
RP Ahmed, A (reprint author), Childrens Mercy Hosp & Clin, 2401 Gillham Rd, Kansas City, MO 64108 USA.
EM aahmed@cmh.edu
OI Ahmed, Atif/0000-0002-8791-5785
NR 27
TC 2
Z9 2
U1 0
U2 3
PU SPRINGER-VERLAG ITALIA SRL
PI MILAN
PA VIA DECEMBRIO, 28, MILAN, 20137, ITALY
SN 1699-048X
EI 1699-3055
J9 CLIN TRANSL ONCOL
JI Clin. Transl. Oncol.
PD NOV
PY 2013
VL 15
IS 11
BP 953
EP 958
DI 10.1007/s12094-013-1030-4
PG 6
WC Oncology
SC Oncology
GA 235BQ
UT WOS:000325690100014
PM 23553333
ER
PT J
AU Tumaini, B
Lee, DW
Lin, TS
Castiello, L
Stroncek, DF
Mackall, C
Wayne, A
Sabatino, M
AF Tumaini, Barbara
Lee, Daniel W.
Lin, Tasha
Castiello, Luciano
Stroncek, David F.
Mackall, Crystal
Wayne, Alan
Sabatino, Marianna
TI Simplified process for the production of anti-CD19-CAR-engineered T
cells
SO CYTOTHERAPY
LA English
DT Article
DE adoptive cellular immunotherapy; CD19 antigen; genetic engineering;
genetic transduction; precursor cell lymphoblastic leukemia-lymphoma
ID CHIMERIC-ANTIGEN-RECEPTOR; RETROVIRAL GENE MARKING; METASTATIC MELANOMA;
CANCER REGRESSION; ANTITUMOR LYMPHOCYTES; CD19 ANTIGEN; THERAPY;
ANTIBODY; IMMUNOTHERAPY; LYMPHOMA
AB Background aims. Adoptive immunotherapy with the use of chimeric antigen receptor (CAR)-engineered T cells specific for CD 19 has shown promising results for the treatment of B-cell lymphomas and leukemia. This therapy involves the transduction of autologous T cells with a viral vector and the subsequent cell expansion. We describe a new, simplified method to produce anti-CD 19-CAR T cells. Methods. T cells were isolated from peripheral blood mononuclear cell (PBMC) with anti-CD3/anti-CD28 paramagnetic beads. After 2 days, the T cells were added to culture bags pre-treated with RetroNectin and loaded with the retroviral anti-CD 19 CAR vector. The cells, beads and vector were incubated for 24 h, and a second transduction was then performed. No spinoculation was used. Cells were then expanded for an additional 9 days. Results. The method was validated through the use of two PBMC products from a patient with B-cell chronic lymphoblastic leukemia and one PBMC product from a healthy subject. The two PBMC products from the patient with B-cell chronic lymphoblastic leukemia contained 11.4% and 12.9% T cells. The manufacturing process led to final products highly enriched in T cells with a mean CD3+ cell content of 98%, a mean expansion of 10.6-fold and a mean transduction efficiency of 68%. Similar results were obtained from the PBMCs of the first four patients with acute lymphoblastic leukemia treated at our institution. Conclusions. We developed a simplified, semi-closed system for the initial selection, activation, transduction and expansion of T cells with the use of anti-CD3/anti-CD28 beads and bags to produce autologous anti-CD19 CAR transduced T cells to support an ongoing clinical trial.
C1 [Tumaini, Barbara; Castiello, Luciano; Stroncek, David F.; Sabatino, Marianna] NIH, Cell Proc Sect, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA.
[Lee, Daniel W.; Lin, Tasha; Mackall, Crystal; Wayne, Alan] NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA.
RP Sabatino, M (reprint author), NIH, Dept Transfus Med, Cell Proc Sect, 10 Ctr Dr MSC 1288,Bldg 10,Room 3C720, Bethesda, MD 20892 USA.
EM sabatinom@cc.nih.gov
RI Castiello, Luciano/K-8616-2016
OI Castiello, Luciano/0000-0001-7146-3158
FU Intramural Research Program of the National Institutes of Health,
Clinical Center; National Cancer Institute
FX The authors would like to thank Dr Steven A. Rosenberg for providing
clinical grade vector. This research was supported by the Intramural
Research Program of the National Institutes of Health, Clinical Center
and National Cancer Institute.
NR 29
TC 15
Z9 16
U1 0
U2 17
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1465-3249
EI 1477-2566
J9 CYTOTHERAPY
JI Cytotherapy
PD NOV
PY 2013
VL 15
IS 11
BP 1406
EP 1415
DI 10.1016/j.jcyt.2013.06.003
PG 10
WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell
Biology; Hematology; Medicine, Research & Experimental
SC Cell Biology; Biotechnology & Applied Microbiology; Hematology; Research
& Experimental Medicine
GA 235PI
UT WOS:000325732800010
PM 23992830
ER
PT J
AU Koulaouzidis, A
Karargyris, A
Rondonotti, E
Noble, CL
Douglas, S
Alexandridis, E
Zahid, AM
Bathgate, AJ
Trimble, KC
Plevris, JN
AF Koulaouzidis, Anastasios
Karargyris, Alexandros
Rondonotti, Emanuele
Noble, Colin L.
Douglas, Sarah
Alexandridis, Efstratios
Zahid, Ali M.
Bathgate, Andrew J.
Trimble, Ken C.
Plevris, John N.
TI Three-dimensional representation software as image enhancement tool in
small-bowel capsule endoscopy: A feasibility study
SO DIGESTIVE AND LIVER DISEASE
LA English
DT Article
DE Capsule endoscopy; Enhancement; Feasibility; Inflammatory; Polyps;
Reconstruction; Small bowel; Software; Three-dimensional; Vascular
ID VIRTUAL CHROMOENDOSCOPY; RECONSTRUCTION; SHAPE; LESIONS
AB Background: Three-dimensional imaging in capsule endoscopy is not currently feasible due to hardware limitations. However, software algorithms that enable three-dimensional reconstruction in capsule endoscopy are available.
Methods: Feasibility study. A phantom was designed to test the accuracy of three-dimensional reconstruction. Thereafter, 192 small-bowel capsule endoscopy images (of vascular: 50; inflammatory: 73; protruding structures: 69) were reviewed with the aid of a purpose-built three-dimensional reconstruction software. Seven endoscopists rated visualisation improved or non-improved. Subgroup analyses performed for diagnostic category, diagnosis, image surface morphology and colour and SBCE equipment used (PillCam (R) vs. MiroCam (R)).
Results: Overall, phantom experiments showed that the three-dimensional reconstruction software was accurate at 90% of red, 70% of yellow and 45% of white phantom models. Enhanced visualisation for 56% of vascular, 23% of inflammatory and <10% of protruding structures was noted (P = 0.007, 0.172 and 0.008, respectively). Furthermore, three-dimensional software application enhanced 53.7% of red, 21.8% of white, 17.3% of red and white, and 9.2% of images of lesions with colour similar to that of the surrounding mucosa, P < 0.0001.
Conclusions: Application of a three-dimensional reconstruction software in capsule endoscopy leads to image enhancement for a significant proportion of vascular, but less so for inflammatory and protruding lesions. Until optics technology allows hardware-enabled three-dimensional reconstruction, it seems a plausible alternative. Crown Copyright (C) 2013 Published by Elsevier Ltd on behalf of Editrice Gastroenterologica Italiana S.r.l. All rights reserved.
C1 [Koulaouzidis, Anastasios; Douglas, Sarah; Alexandridis, Efstratios; Zahid, Ali M.; Bathgate, Andrew J.; Trimble, Ken C.; Plevris, John N.] Royal Infirm, Ctr Liver & Digest Disorders, Edinburgh EH16 4SA, Midlothian, Scotland.
[Karargyris, Alexandros] NIH, Natl Lib Med, Bethesda, MD 20892 USA.
[Rondonotti, Emanuele] Osped Valduce, Gastroenterol Unit, Como, Italy.
[Noble, Colin L.] Western Gen Hosp, Gastrointestinal Unit, Edinburgh EH4 2XU, Midlothian, Scotland.
[Plevris, John N.] Univ Edinburgh, Sch Med, Edinburgh, Midlothian, Scotland.
RP Koulaouzidis, A (reprint author), Royal Infirm, Endoscopy Unit, 51 Little France Crescent,Old Dalkeith Rd, Edinburgh EH16 4SA, Midlothian, Scotland.
EM akoulaouzidis@hotmail.com
FU Given Imaging Ltd., Germany; Fujinong
FX Dr A. Koulaouzidis has received research support from Given Imaging
Ltd., Germany (Given (R) Imaging-ESGE Research Grant 2011), unrelated
though to the present work.; Dr E. Alexandridis has received research
support from Fujinong, unrelated to present work.
NR 24
TC 12
Z9 12
U1 0
U2 8
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1590-8658
EI 1878-3562
J9 DIGEST LIVER DIS
JI Dig. Liver Dis.
PD NOV
PY 2013
VL 45
IS 11
BP 909
EP 914
DI 10.1016/j.dld.2013.05.013
PG 6
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 233YE
UT WOS:000325604700009
PM 23849802
ER
PT J
AU Chowell, G
Viboud, C
AF Chowell, Gerardo
Viboud, Cecile
TI Lessons Learned from Case Fatality Risk Estimates of 2009 Pandemic
Influenza
SO EPIDEMIOLOGY
LA English
DT Editorial Material
ID A H1N1 VIRUS; CIRCULATION; INFECTION; MORTALITY; SEVERITY; A/H1N1
C1 [Chowell, Gerardo] Arizona State Univ, Sch Human Evolut & Social Change, Tempe, AZ 85287 USA.
[Chowell, Gerardo; Viboud, Cecile] NIH, Div Epidemiol & Populat Studies, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Chowell, G (reprint author), Arizona State Univ, Sch Human Evolut & Social Change, 900 S Cady Mall,Rm 233, Tempe, AZ 85287 USA.
EM gchowell@asu.edu
FU Intramural NIH HHS [Z99 TW999999]
NR 17
TC 2
Z9 2
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1044-3983
EI 1531-5487
J9 EPIDEMIOLOGY
JI Epidemiology
PD NOV
PY 2013
VL 24
IS 6
BP 842
EP 844
DI 10.1097/01.ede.0000434434.52506.bc
PG 3
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 232YH
UT WOS:000325530100007
PM 24076991
ER
PT J
AU Li, D
Longnecker, MP
Dunson, DB
AF Li, Daniel
Longnecker, Matthew P.
Dunson, David B.
TI Lipid Adjustment for Chemical Exposures Accounting for Concomitant
Variables
SO EPIDEMIOLOGY
LA English
DT Article
ID ADIPOSE-TISSUE; BREAST-CANCER; HUMAN HEALTH; HUMAN-SERUM;
POLYCHLORINATED-BIPHENYLS; ORGANOCHLORINE COMPOUNDS; PCB CONGENERS;
CORD-BLOOD; WOMEN; RISK
AB Background: Some environmental chemical exposures are lipophilic and need to be adjusted by serum lipid levels before data analyses. There are currently various strategies that attempt to account for this problem, but all have their drawbacks. To address such concerns, we propose a new method that uses Box-Cox transformations and a simple Bayesian hierarchical model to adjust for lipophilic chemical exposures.
Methods: We compared our Box-Cox method to existing methods. We ran simulation studies in which increasing levels of lipid-adjusted chemical exposure did and did not increase the odds of having a disease, and we looked at both single-exposure and multiple-exposure cases. We also analyzed an epidemiology dataset that examined the effects of various chemical exposure on the risk of birth defects.
Results: Compared with existing methods, our Box-Cox method produced unbiased estimates, good coverage, similar power, and lower type I error rates. This was the case in both single- and multiple-exposure simulation studies. Results from analysis of the birth-defect data differed from results using existing methods.
Conclusion: Our Box-Cox method is a novel and intuitive way to account for the lipophilic nature of certain chemical exposures. It addresses some of the problems with existing methods, is easily extendable to multiple exposures, and can be used in any analysis that involves concomitant variables.
C1 [Li, Daniel; Dunson, David B.] Duke Univ, Dept Stat Sci, Durham, NC 27708 USA.
[Longnecker, Matthew P.] NIEHS, Epidemiol Branch, NIH, DHHS, Res Triangle Pk, NC 27709 USA.
RP Dunson, DB (reprint author), Duke Univ, Box 90251, Durham, NC 27708 USA.
EM dunson@stat.duke.edu
OI Longnecker, Matthew/0000-0001-6073-5322
FU National Institute of Environmental Health Sciences (NIEHS) of the
National Institutes of Health [R01 ES 017240]; NIEHS
FX This research was supported by grant R01 ES 017240 from the National
Institute of Environmental Health Sciences (NIEHS) of the National
Institutes of Health and supported in part by intramural funds from
NIEHS.
NR 26
TC 5
Z9 5
U1 0
U2 10
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1044-3983
EI 1531-5487
J9 EPIDEMIOLOGY
JI Epidemiology
PD NOV
PY 2013
VL 24
IS 6
BP 921
EP 928
DI 10.1097/EDE.0b013e3182a671e4
PG 8
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 232YH
UT WOS:000325530100018
PM 24051893
ER
PT J
AU Hoover, RN
Fraumeni, JF
AF Hoover, Robert N.
Fraumeni, Joseph F., Jr.
TI A Conversation with Joseph F. Fraumeni, Jr.
SO EPIDEMIOLOGY
LA English
DT Editorial Material
ID GENOME-WIDE ASSOCIATION; CANCER SUSCEPTIBILITY LOCI; LUNG-CANCER;
FAMILIAL SYNDROME; BREAST-CANCER; NEOPLASMS; ANIRIDIA; SARCOMAS;
SMOKING; TUMOR
C1 [Hoover, Robert N.] NCI, Epidemiol & Biostat Program, Div Canc Epidemiol & Genet, Bethesda, MD USA.
RP Hoover, RN (reprint author), NCI, Epidemiol & Biostat Program, Div Canc Epidemiol & Genet, 9609 Med Ctr Dr,Room 7E-584 MSC 9773, Bethesda, MD USA.
EM hooverr@mail.nih.gov
NR 17
TC 0
Z9 0
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1044-3983
EI 1531-5487
J9 EPIDEMIOLOGY
JI Epidemiology
PD NOV
PY 2013
VL 24
IS 6
BP 929
EP 933
DI 10.1097/EDE.0b013e3182a56987
PG 5
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 232YH
UT WOS:000325530100019
ER
PT J
AU Siddiqui, MM
Rais-Bahrami, S
Truong, H
Stamatakis, L
Vourganti, S
Nix, J
Hoang, AN
Walton-Diaz, A
Shuch, B
Weintraub, M
Kruecker, J
Amalou, H
Turkbey, B
Merino, MJ
Choyke, PL
Wood, BJ
Pinto, PA
AF Siddiqui, M. Minhaj
Rais-Bahrami, Soroush
Hong Truong
Stamatakis, Lambros
Vourganti, Srinivas
Nix, Jeffrey
Hoang, Anthony N.
Walton-Diaz, Annerleim
Shuch, Brian
Weintraub, Michael
Kruecker, Jochen
Amalou, Hayet
Turkbey, Baris
Merino, Maria J.
Choyke, Peter L.
Wood, Bradford J.
Pinto, Peter A.
TI Magnetic Resonance Imaging/Ultrasound-Fusion Biopsy Significantly
Upgrades Prostate Cancer Versus Systematic 12-core Transrectal
Ultrasound Biopsy
SO EUROPEAN UROLOGY
LA English
DT Article
DE Image-guided biopsy; Targeted biopsy; Magnetic resonance imaging;
Prostate cancer; Prostatic neoplasms/diagnosis; Prostatic
neoplasms/pathology; Prostatic neoplasms/; ultrasonography
ID GLEASON SCORE; ACCURACY
AB Background: Gleason scores from standard, 12-core prostate biopsies are upgraded historically in 25-33% of patients. Multiparametric prostate magnetic resonance imaging (MP-MRI) with ultrasound (US)-targeted fusion biopsy may better sample the true gland pathology.
Objective: The rate of Gleason score upgrading from an MRI/US-fusion-guided prostate-biopsy platform is compared with a standard 12-core biopsy regimen alone.
Design, setting, and participants: There were 582 subjects enrolled from August 2007 through August 2012 in a prospective trial comparing systematic, extended 12-core transrectal ultrasound biopsies to targeted MRI/US-fusion-guided prostate biopsies performed during the same biopsy session.
Outcome measurements and statistical analysis: The highest Gleason score from each biopsy method was compared.
Interventions: An MRI/US-fusion-guided platform with electromagnetic tracking was used for the performance of the fusion-guided biopsies.
Results and limitations: A diagnosis of prostate cancer (PCa) was made in 315 (54%) of the patients. Addition of targeted biopsy led to Gleason upgrading in 81 (32%) cases. Targeted biopsy detected 67% more Gleason >= 4 + 3 tumors than 12-core biopsy alone and missed 36% of Gleason <= 3 + 4 tumors, thus mitigating the detection of lower-grade disease. Conversely, 12-core biopsy led to upgrading in 67 (26%) cases over targeted biopsy alone but only detected 8% more Gleason >= 4 + 3 tumors. On multivariate analysis, MP-MRI suspicion was associated with Gleason score upgrading in the targeted lesions (p < 0.001). The main limitation of this study was that definitive pathology from radical prostatectomy was not available.
Conclusions: MRI/US-fusion-guided biopsy upgrades and detects PCa of higher Gleason score in 32% of patients compared with traditional 12-core biopsy alone. Targeted biopsy technique preferentially detects higher-grade PCa while missing lower-grade tumors. (C) 2013 Published by Elsevier B.V. on behalf of European Association of Urology.
C1 [Siddiqui, M. Minhaj; Rais-Bahrami, Soroush; Hong Truong; Stamatakis, Lambros; Vourganti, Srinivas; Nix, Jeffrey; Hoang, Anthony N.; Walton-Diaz, Annerleim; Shuch, Brian; Weintraub, Michael; Pinto, Peter A.] NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Turkbey, Baris; Choyke, Peter L.] NCI, Mol Imaging Program, NIH, Bethesda, MD 20892 USA.
[Amalou, Hayet; Wood, Bradford J.; Pinto, Peter A.] NCI, Ctr Intervent Oncol, NIH, Bethesda, MD 20892 USA.
[Kruecker, Jochen] Philips Res North Amer, Briarcliff Manor, NY USA.
[Merino, Maria J.] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA.
RP Pinto, PA (reprint author), NCI, Urol Oncol Branch, NIH, 10 Ctr Dr,MSC 1210,Bldg 10,CRC Room 2W-5940, Bethesda, MD 20892 USA.
EM pintop@mail.nih.gov
OI Siddiqui, Mohummad/0000-0002-4484-6820; Rais-Bahrami,
Soroush/0000-0001-9466-9925
FU US National Institutes of Health (NIH), National Cancer Institute,
Center for Cancer Research; NIH; Pfizer Inc; Leona M. and Harry B.
Helmsley Charitable Trust; Howard Hughes Medical Institute
FX This research was supported by the Intramural Research Program of the US
National Institutes of Health (NIH), National Cancer Institute, Center
for Cancer Research. NIH and Philips Healthcare have a cooperative
research and development agreement. NIH and Philips share intellectual
property in the field. This research was also made possible through the
NIH Medical Research Scholars Program, a public-private partnership
supported jointly by the NIH and generous contributions to the
Foundation for the NIH from Pfizer Inc, the Leona M. and Harry B.
Helmsley Charitable Trust, and the Howard Hughes Medical Institute, as
well as other private donors. For a complete list, please visit the
Foundation Web site at
http://www.fnih.org/work/programs-development/medical-research-scholars-
program.
NR 16
TC 183
Z9 188
U1 3
U2 26
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0302-2838
EI 1873-7560
J9 EUR UROL
JI Eur. Urol.
PD NOV
PY 2013
VL 64
IS 5
BP 713
EP 719
DI 10.1016/j.eururo.2013.05.059
PG 7
WC Urology & Nephrology
SC Urology & Nephrology
GA 232FT
UT WOS:000325478100011
PM 23787357
ER
PT J
AU Addolorato, G
Mirijello, A
Leggio, L
AF Addolorato, Giovanni
Mirijello, Antonio
Leggio, Lorenzo
TI Alcohol addiction: toward a patient-oriented pharmacological treatment
SO EXPERT OPINION ON PHARMACOTHERAPY
LA English
DT Editorial Material
DE alcohol use disorder; drug treatment
ID DEPENDENT PATIENTS; NALTREXONE RESPONSE; CONTROLLED-TRIAL; DOUBLE-BLIND;
BACLOFEN; SAFETY; ONDANSETRON; ABSTINENCE; EFFICACY
AB Very few medications (i.e., disulfiram, naltrexone and acamprosate) are approved for the treatment of alcoholism and their effects are suboptimal. The development of new effective and safe pharmacological agents to treat alcoholic patients is crucial, together with the need to identify predictors of outcomes in different subsets of patients.
C1 [Addolorato, Giovanni; Mirijello, Antonio] Univ Cattolica Sacro Cuore, Dept Internal Med, Gemelli Hosp, I-00168 Rome, Italy.
[Leggio, Lorenzo] NIAAA, Sect Clin Psychoneuroendocrinol & Neuropsychophar, Lab Clin & Translat Studies, NIH, Bethesda, MD USA.
[Leggio, Lorenzo] NIDA, Intramural Res Program, NIH, Baltimore, MD USA.
[Leggio, Lorenzo] Brown Univ, Dept Behav & Social Sci, Providence, RI 02912 USA.
RP Addolorato, G (reprint author), Univ Cattolica Sacro Cuore, Dept Internal Med, I-00168 Rome, Italy.
EM g.addolorato@rm.unicatt.it
RI Leggio, Lorenzo/M-2972-2016; Mirijello, Antonio/C-4103-2017;
OI Mirijello, Antonio/0000-0003-3932-3803; Addolorato,
Giovanni/0000-0002-1522-9946
FU Intramural NIH HHS [Z99 AA999999]
NR 14
TC 6
Z9 6
U1 1
U2 8
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1465-6566
EI 1744-7666
J9 EXPERT OPIN PHARMACO
JI Expert Opin. Pharmacother.
PD NOV
PY 2013
VL 14
IS 16
BP 2157
EP 2160
DI 10.1517/14656566.2013.834047
PG 4
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 232UZ
UT WOS:000325521200001
PM 23984836
ER
PT J
AU Aliaga, L
Lai, C
Yu, J
Chub, N
Shim, H
Sun, LX
Xie, CS
Yang, WJ
Lin, X
O'Donovan, MJ
Cai, HB
AF Aliaga, Leonardo
Lai, Chen
Yu, Jia
Chub, Nikolai
Shim, Hoon
Sun, Lixin
Xie, Chengsong
Yang, Wan-Jou
Lin, Xian
O'Donovan, Michael J.
Cai, Huaibin
TI Amyotrophic lateral sclerosis-related VAPB P56S mutation differentially
affects the function and survival of corticospinal and spinal motor
neurons
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID UNFOLDED-PROTEIN RESPONSE; CEREBRAL-CORTEX; EPH RECEPTORS; MICE; STRESS;
DEGENERATION; MUTANT; CORD; ER; AGGREGATION
AB The substitution of Proline with Serine at residue 56 (P56S) of vesicle-associated membrane protein-associated protein B (VAPB) has been linked to an atypical autosomal dominant form of familial amyotrophic lateral sclerosis 8 (ALS8). To investigate the pathogenic mechanism of P56S VAPB in ALS, we generated transgenic (Tg) mice that heterologously express human wild-type (WT) and P56S VAPB under the control of a pan-neuronal promoter Thy1.2. While WT VAPB Tg mice did not exhibit any overt motor behavioral phenotypes, P56S VAPB Tg mice developed progressive hyperactivities and other motor abnormalities. VAPB protein was accumulated as large punctate in the soma and proximal dendrites of both corticospinal motor neurons (CSMNs) and spinal motor neurons (SMNs) in P56S VAPB Tg mice. Concomitantly, a significant increase of endoplasmic reticulum stress and unfolded protein response and the resulting up-regulation of pro-apoptotic factor CCAAT/enhancer-binding protein homologous protein expression were observed in the CSMNs and SMNs of P56S VAPB Tg mice. However, only a progressive loss of CSMNs but not SMNs was found in P56S VAPB Tg mice. In SMNs, P56S VAPB promoted a rather selective translocation of VAPB protein onto the postsynaptic site of C-boutons that altered the morphology of C-boutons and impaired the spontaneous rhythmic discharges of SMNs. Therefore, these findings provide new pathophysiological mechanisms of P56S VAPB that differentially affect the function and survival of CSMNs and SMNs in ALS8.
C1 [Aliaga, Leonardo; Lai, Chen; Yu, Jia; Shim, Hoon; Sun, Lixin; Xie, Chengsong; Yang, Wan-Jou; Lin, Xian; Cai, Huaibin] NIA, Transgen Sect, Neurogenet Lab, Bethesda, MD 20892 USA.
[Chub, Nikolai; O'Donovan, Michael J.] NINDS, Dev Neurobiol Sect, Neural Control Lab, NIH, Bethesda, MD 20892 USA.
RP Cai, HB (reprint author), NIA, Transgen Sect, Neurogenet Lab, NIH, Bldg 35,Room 1A116,MSC 3707,35 Convent Dr, Bethesda, MD 20892 USA.
EM caih@mail.nih.gov
RI Yu, Jia/J-2792-2014; o'donovan, michael/A-2357-2015
OI o'donovan, michael/0000-0003-2487-7547
FU National Institute on Aging [AG000943]; National Institute of
Neurological Disorders and Stroke at NIH
FX This work was supported in part by the intramural research programs of
National Institute on Aging (AG000943, H. C.) and National Institute of
Neurological Disorders and Stroke at NIH. L. A. was an Howard Hugh
Medical Institute Scholar.
NR 36
TC 17
Z9 17
U1 0
U2 2
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0964-6906
EI 1460-2083
J9 HUM MOL GENET
JI Hum. Mol. Genet.
PD NOV 1
PY 2013
VL 22
IS 21
BP 4293
EP 4305
DI 10.1093/hmg/ddt279
PG 13
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 236CN
UT WOS:000325771500005
PM 23771029
ER
PT J
AU Bian, L
Traurig, M
Hanson, RL
Marinelarena, A
Kobes, S
Muller, YL
Malhotra, A
Huang, K
Perez, J
Gale, A
Knowler, WC
Bogardus, C
Baier, LJ
AF Bian, Li
Traurig, Michael
Hanson, Robert L.
Marinelarena, Alejandra
Kobes, Sayuko
Muller, Yunhua L.
Malhotra, Alka
Huang, Ke
Perez, Jessica
Gale, Alex
Knowler, William C.
Bogardus, Clifton
Baier, Leslie J.
TI MAP2K3 is associated with body mass index in American Indians and
Caucasians and may mediate hypothalamic inflammation
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID RECENT SEGMENTAL DUPLICATIONS; NONOBESE PIMA-INDIANS; LARGE GENE LISTS;
ADIPOCYTE DIFFERENTIATION; HUMAN-GENOME; INCREASED EXPRESSION;
FEEDING-BEHAVIOR; FOOD-INTAKE; OBESITY; KINASE
AB To identify genes that affect body mass index (BMI) in American Indians who are predominately of Pima Indian heritage, we previously completed a genome-wide association study in 1120 American Indians. That study also included follow-up genotyping for 9 SNPs in 2133 additional subjects. A comprehensive follow-up study has subsequently been completed where 292 SNPs were genotyped in 3562 subjects, of which 128 SNPs were assessed for replication in 3238 additional subjects. In the combined subjects (n 6800), BMI associations for two SNPs, rs12882548 and rs11652094, approached genome-wide significance (P 6.7 10(7) and 8.1 10(7), respectively). Rs12882548 is located in a gene desert on chromosome 14 and rs11652094 maps near MAP2K3. Several SNPs in the MAP2K3 region including rs11652094 were also associated with BMI in Caucasians from the GIANT consortium (P 10(2)10(5)), and the combined P-values across both American Indians and Caucasian were P 10(4)10(9). Follow-up sequencing across MAP2K3 identified several paralogous sequence variants indicating that the region may have been duplicated. MAP2K3 expression levels in adipose tissue biopsies were positively correlated with BMI, although it is unclear if this correlation is a cause or effect. In vitro studies with cloned MAP2K3 promoters suggest that MAP2K3 expression may be up-regulated during adipogenesis. Microarray analyses of mouse hypothalamus cells expressing constitutively active MAP2K3 identified several up-regulated genes involved in immune/inflammatory pathways and a gene, Hap1, thought to play a role in appetite regulation. We conclude that MAP2K3 is a reproducible obesity locus that may affect body weight via complex mechanisms involving appetite regulation and hypothalamic inflammation.
C1 NIDDK, Diabet Mol Genet Sect, Phoenix Epidemiol & Clin Res Branch, NIH, Phoenix, AZ 85004 USA.
NIDDK, Diabet Epidemiol & Clin Res Sect, Phoenix Epidemiol & Clin Res Branch, NIH, Phoenix, AZ 85004 USA.
RP Baier, LJ (reprint author), NIDDK, Diabet Mol Genet Sect, NIH, 455 North 5th St, Phoenix, AZ 85004 USA.
EM lbaier@phx.niddk.nih.gov
RI Hanson, Robert/O-3238-2015
OI Hanson, Robert/0000-0002-4252-7068
FU National Institute of Diabetes and Digestive and Kidney Diseases,
National Institutes of Health; NIDDK, NIH
FX This work was supported by the intramural research program of the
National Institute of Diabetes and Digestive and Kidney Diseases,
National Institutes of Health. Funding to pay the Open Access
publication charges for this article was provided by The Intramural
Program of NIDDK, NIH.
NR 51
TC 9
Z9 9
U1 0
U2 6
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 2013
VL 22
IS 21
BP 4438
EP 4449
DI 10.1093/hmg/ddt291
PG 12
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 236CN
UT WOS:000325771500018
PM 23825110
ER
PT J
AU Gonzalez-Perez, M
Marino-Ramirez, L
Parra-Lopez, CA
Murcia, MI
Marquina, B
Mata-Espinoza, D
Rodriguez-Miguez, Y
Baay-Guzman, GJ
Huerta-Yepez, S
Hernandez-Pando, R
AF Gonzalez-Perez, Monica
Marino-Ramirez, Leonardo
Parra-Lopez, Carlos Alberto
Murcia, Martha Isabel
Marquina, Brenda
Mata-Espinoza, Dulce
Rodriguez-Miguez, Yadira
Baay-Guzman, Guillermina J.
Huerta-Yepez, Sara
Hernandez-Pando, Rogelio
TI Virulence and Immune Response Induced by Mycobacterium avium Complex
Strains in a Model of Progressive Pulmonary Tuberculosis and
Subcutaneous Infection in BALB/c Mice
SO INFECTION AND IMMUNITY
LA English
DT Article
ID TUMOR-NECROSIS-FACTOR; NON-HIV PATIENTS; NONTUBERCULOUS MYCOBACTERIA;
MURINE MODEL; SP-NOV.; IDENTIFICATION; PATHOGENESIS; COLOMBIENSE;
MACROPHAGES; DISEASE
AB The genus Mycobacterium comprises more than 150 species, including important pathogens for humans which cause major public health problems. The vast majority of efforts to understand the genus have been addressed in studies with Mycobacterium tuberculosis. The biological differentiation between M. tuberculosis and nontuberculous mycobacteria (NTM) is important because there are distinctions in the sources of infection, treatments, and the course of disease. Likewise, the importance of studying NTM is not only due to its clinical significance but also due to the mechanisms by which some species are pathogenic while others are not. Mycobacterium avium complex (MAC) is the most important group of NTM opportunistic pathogens, since it is the second largest medical complex in the genus after the M. tuberculosis complex. Here, we evaluated the virulence and immune response of M. avium subsp. avium and Mycobacterium colombiense, using experimental models of progressive pulmonary tuberculosis and subcutaneous infection in BALB/c mice. Mice infected intratracheally with a high dose of MAC strains showed high expression of tumor necrosis factor alpha (TNF-alpha) and inducible nitric oxide synthase with rapid bacillus elimination and numerous granulomas, but without lung consolidation during late infection in coexistence with high expression of anti-inflammatory cytokines. In contrast, subcutaneous infection showed high production of the proinflammatory cytokines TNF-alpha and gamma interferon with relatively low production of anti-inflammatory cytokines such as interleukin-10 (IL-10) or IL-4, which efficiently eliminate the bacilli but maintain extensive inflammation and fibrosis. Thus, MAC infection evokes different immune and inflammatory responses depending on the MAC species and affected tissue.
C1 [Gonzalez-Perez, Monica; Marino-Ramirez, Leonardo; Parra-Lopez, Carlos Alberto; Murcia, Martha Isabel] Univ Nacl Colombia, Sch Med, Dept Microbiol, Bogota, Colombia.
[Gonzalez-Perez, Monica; Marquina, Brenda; Mata-Espinoza, Dulce; Rodriguez-Miguez, Yadira; Hernandez-Pando, Rogelio] Natl Inst Med Sci & Nutr, Dept Pathol, Expt Pathol Sect, Mexico City, DF, Mexico.
[Marino-Ramirez, Leonardo] NIH, Computat Biol Branch, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA.
[Gonzalez-Perez, Monica; Marino-Ramirez, Leonardo] PanAmer Bioinformat Inst, Santa Marta, Magdalena, Colombia.
[Baay-Guzman, Guillermina J.; Huerta-Yepez, Sara] Pediat Hosp Mexico Federico Gomez, Oncol Res Unit, Mexico City, DF, Mexico.
RP Hernandez-Pando, R (reprint author), Natl Inst Med Sci & Nutr, Dept Pathol, Expt Pathol Sect, Mexico City, DF, Mexico.
EM rhdezpando@hotmail.com
OI Marino-Ramirez, Leonardo/0000-0002-5716-8512
FU Intramural Research Program of the National Institutes of Health;
National Library of Medicine; National Center for Biotechnology
Information; CONACyT [84456]; National University of Colombia [15129]
FX This study was supported in part by the Intramural Research Program of
the National Institutes of Health, National Library of Medicine,
National Center for Biotechnology Information, and CONACyT (grant
84456). M.G.-P. was supported by the National University of Colombia
(Convocatoria Apoyo de la DIB a Tesis de Investigacion en
Posgrados-Quinto Corte; Proyecto 15129).
NR 67
TC 4
Z9 5
U1 0
U2 9
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 2013
VL 81
IS 11
BP 4001
EP 4012
DI 10.1128/IAI.00150-13
PG 12
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 235LI
UT WOS:000325719900006
PM 23959717
ER
PT J
AU Robertson, GT
Child, R
Ingle, C
Celli, J
Norgard, MV
AF Robertson, Gregory T.
Child, Robert
Ingle, Christine
Celli, Jean
Norgard, Michael V.
TI IglE Is an Outer Membrane-Associated Lipoprotein Essential for
Intracellular Survival and Murine Virulence of Type A Francisella
tularensis
SO INFECTION AND IMMUNITY
LA English
DT Article
ID VI SECRETION SYSTEM; HUMAN MACROPHAGES; SCHU S4; PSEUDOMONAS-AERUGINOSA;
SUBSP TULARENSIS; LIVE VACCINE; IFN-GAMMA; PROTEIN; ACTIVATION;
PHAGOSOME
AB IglE is a small, hypothetical protein encoded by the duplicated Francisella pathogenicity island (FPI). Inactivation of both copies of iglE rendered Francisella tularensis subsp. tularensis Schu S4 avirulent and incapable of intracellular replication, owing to an inability to escape the phagosome. This defect was fully reversed following single-copy expression of iglE in trans from attTn7 under the control of the Francisella rpsL promoter, thereby establishing that the loss of iglE, and not polar effects on downstream vgrG gene expression, was responsible for the defect. IglE is exported to the Francisella outer membrane as an similar to 13.9-kDa lipoprotein, determined on the basis of a combination of selective Triton X-114 solubilization, radiolabeling with [H-3]palmitic acid, and sucrose density gradient membrane partitioning studies. Lastly, a genetic screen using the iglE-null live vaccine strain resulted in the identification of key regions in the carboxyl terminus of IglE that are required for intracellular replication of Francisella tularensis in J774A.1 macrophages. Thus, IglE is essential for Francisella tularensis virulence. Our data support a model that likely includes protein-protein interactions at or near the bacterial cell surface that are unknown at present.
C1 [Robertson, Gregory T.; Ingle, Christine; Norgard, Michael V.] Univ Texas SW Med Ctr Dallas, Dept Microbiol, Dallas, TX 75390 USA.
[Child, Robert; Celli, Jean] NIAID, Tularemia Pathogenesis Sect, Intracellular Parasites Lab, NIH,Rocky Mt Labs, Hamilton, MT USA.
RP Norgard, MV (reprint author), Univ Texas SW Med Ctr Dallas, Dept Microbiol, Dallas, TX 75390 USA.
EM Michael.Norgard@UTSouthwestern.edu
RI Robertson, Gregory/E-1601-2017
OI Robertson, Gregory/0000-0001-7157-4034
FU National Institute of Allergy and Infectious Diseases (NIAID), NIH [U54
AI057156]
FX This work was supported by grant number U54 AI057156 from the National
Institute of Allergy and Infectious Diseases (NIAID), NIH.
NR 66
TC 10
Z9 10
U1 0
U2 4
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0019-9567
EI 1098-5522
J9 INFECT IMMUN
JI Infect. Immun.
PD NOV
PY 2013
VL 81
IS 11
BP 4026
EP 4040
DI 10.1128/IAI.00595-13
PG 15
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 235LI
UT WOS:000325719900008
PM 23959721
ER
PT J
AU Spinner, JL
Carmody, AB
Jarrett, CO
Hinnebusch, BJ
AF Spinner, Justin L.
Carmody, Aaron B.
Jarrett, Clayton O.
Hinnebusch, B. Joseph
TI Role of Yersinia pestis Toxin Complex Family Proteins in Resistance to
Phagocytosis by Polymorphonuclear Leukocytes
SO INFECTION AND IMMUNITY
LA English
DT Article
ID BACTERIUM PHOTORHABDUS-LUMINESCENS; OUTER-MEMBRANE PROTEINS; LOW-CALCIUM
RESPONSE; INSECTICIDAL TOXIN; GENE-EXPRESSION; III SECRETION;
PLASMINOGEN-ACTIVATOR; ESCHERICHIA-COLI; GLOBAL CHANGES; ORAL TOXICITY
AB Yersinia pestis carries homologues of the toxin complex (Tc) family proteins, which were first identified in other Gram-negative bacteria as having potent insecticidal activity. The Y. pestis Tc proteins are neither toxic to fleas nor essential for survival of the bacterium in the flea, even though tc gene expression is highly upregulated and much more of the Tc proteins YitA and YipA are produced in the flea than when Y. pestis is grown in vitro. We show that Tc+ and Tc- Y. pestis strains are transmitted equivalently from coinfected fleas, further demonstrating that the Tc proteins have no discernible role, either positive or negative, in transmission by the flea vector. Tc proteins did, however, confer Y. pestis with increased resistance to killing by polymorphonuclear leukocytes (PMNs). Resistance to killing was not the result of decreased PMN viability or increased intracellular survival but instead correlated with a Tc protein-dependent resistance to phagocytosis that was independent of the type III secretion system (T3SS). Correspondingly, we did not detect T3SS-dependent secretion of the native Tc proteins YitA and YipA or the translocation of YitA- or YipA-beta-lactamase fusion proteins into CHO-K1 (CHO) cells or human PMNs. Thus, although highly produced by Y. pestis within the flea and related to insecticidal toxins, the Tc proteins do not affect interaction with the flea or transmission. Rather, the Y. pestis Tc proteins inhibit phagocytosis by mouse PMNs, independent of the T3SS, and may be important for subverting the mammalian innate immune response immediately following transmission from the flea.
C1 [Spinner, Justin L.; Jarrett, Clayton O.; Hinnebusch, B. Joseph] NIAID, Lab Zoonot Pathogens, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA.
[Carmody, Aaron B.] NIAID, Flow Cytometry Unit, Res Technol Sect, Rocky Mt Labs,NIH, Hamilton, MT USA.
RP Spinner, JL (reprint author), NIAID, Lab Zoonot Pathogens, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA.
EM Justin.Spinner@nih.gov
FU Intramural Research Program of the NIAID, NIH
FX This research was supported by the Intramural Research Program of the
NIAID, NIH.
NR 53
TC 5
Z9 5
U1 0
U2 3
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 2013
VL 81
IS 11
BP 4041
EP 4052
DI 10.1128/IAI.00648-13
PG 12
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 235LI
UT WOS:000325719900009
PM 23959716
ER
PT J
AU Ito, D
Hasegawa, T
Miura, K
Yamasaki, T
Arumugam, TU
Thongkukiatkul, A
Takeo, S
Takashima, E
Sattabongkot, J
Han, ET
Long, CA
Torii, M
Tsuboi, T
AF Ito, Daisuke
Hasegawa, Tomoyuki
Miura, Kazutoyo
Yamasaki, Tsutomu
Arumugam, Thangavelu U.
Thongkukiatkul, Amporn
Takeo, Satoru
Takashima, Eizo
Sattabongkot, Jetsumon
Han, Eun-Taek
Long, Carole A.
Torii, Motomi
Tsuboi, Takafumi
TI RALP1 Is a Rhoptry Neck Erythrocyte-Binding Protein of Plasmodium
falciparum Merozoites and a Potential Blood-Stage Vaccine Candidate
Antigen
SO INFECTION AND IMMUNITY
LA English
DT Article
ID MALARIA PARASITES; INVASION; AMA1; DISCOVERY; EVENTS; CELLS; RON2
AB Erythrocyte invasion by merozoites is an obligatory stage of Plasmodium infection and is essential to disease progression. Proteins in the apical organelles of merozoites mediate the invasion of erythrocytes and are potential malaria vaccine candidates. Rhoptry-associated, leucine zipper-like protein 1 (RALP1) of Plasmodium falciparum was previously found to be specifically expressed in schizont stages and localized to the rhoptries of merozoites by immunofluorescence assay (IFA). Also, RALP1 has been refractory to gene knockout attempts, suggesting that it is essential for blood-stage parasite survival. These characteristics suggest that RALP1 can be a potential blood-stage vaccine candidate antigen, and here we assessed its potential in this regard. Antibodies were raised against recombinant RALP1 proteins synthesized by using the wheat germ cell-free system. Immunoelectron microscopy demonstrated for the first time that RALP1 is a rhoptry neck protein of merozoites. Moreover, our IFA data showed that RALP1 translocates from the rhoptry neck to the moving junction during merozoite invasion. Growth and invasion inhibition assays revealed that anti-RALP1 antibodies inhibit the invasion of erythrocytes by merozoites. The findings that RALP1 possesses an erythrocyte-binding epitope in the C-terminal region and that anti-RALP1 antibodies disrupt tight-junction formation, are evidence that RALP1 plays an important role during merozoite invasion of erythrocytes. In addition, human sera collected from areas in Thailand and Mali where malaria is endemic recognized this protein. Overall, our findings indicate that RALP1 is a rhoptry neck erythrocyte-binding protein and that it qualifies as a potential blood-stage vaccine candidate.
C1 [Ito, Daisuke; Hasegawa, Tomoyuki; Yamasaki, Tsutomu; Arumugam, Thangavelu U.; Takeo, Satoru; Takashima, Eizo; Tsuboi, Takafumi] Ehime Univ, Div Malaria Res, Proteosci Ctr, Matsuyama, Ehime, Japan.
[Tsuboi, Takafumi] Ehime Univ, Venture Business Lab, Matsuyama, Ehime, Japan.
[Miura, Kazutoyo; Long, Carole A.] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD USA.
[Thongkukiatkul, Amporn] Burapha Univ, Fac Sci, Dept Biol, Chon Buri, Thailand.
[Sattabongkot, Jetsumon] Mahidol Univ, Fac Trop Med, Mahidol Vivax Res Unit, Bangkok, Thailand.
[Han, Eun-Taek] Kangwon Natl Univ, Sch Med, Dept Med Environm Biol & Trop Med, Chunchon, Gangwon Do, South Korea.
[Torii, Motomi] Ehime Univ, Proteosci Ctr, Div Mol Parasitol, Toon, Ehime, Japan.
RP Tsuboi, T (reprint author), Ehime Univ, Div Malaria Res, Proteosci Ctr, Matsuyama, Ehime, Japan.
EM tsuboi@ccr.ehime-u.ac.jp
FU MEXT KAKENHI [23117008]; JSPS KAKENHI in Japan [23406007]; Ministry of
Health, Labor, and Welfare, Japan [H21-Chikyukibo-ippan-005]; NIAID;
NIH; PATH Malaria Vaccine Initiative
FX This work was supported in part by MEXT KAKENHI (23117008) and JSPS
KAKENHI (23406007) in Japan and a grant from the Ministry of Health,
Labor, and Welfare (H21-Chikyukibo-ippan-005), Japan. The study with
Malian samples was supported by the intramural program of the NIAID,
NIH, and by the PATH Malaria Vaccine Initiative.
NR 29
TC 9
Z9 9
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 2013
VL 81
IS 11
BP 4290
EP 4298
DI 10.1128/IAI.00690-13
PG 9
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 235LI
UT WOS:000325719900034
PM 24002067
ER
PT J
AU Mackey-Lawrence, NM
Guo, XT
Sturdevant, DE
Virtaneva, K
Hernandez, MM
Houpt, E
Sher, A
Porcella, SF
Petri, WA
AF Mackey-Lawrence, Nicole M.
Guo, Xiaoti
Sturdevant, Daniel E.
Virtaneva, Kimmo
Hernandez, Matthew M.
Houpt, Eric
Sher, Alan
Porcella, Stephen F.
Petri, William A., Jr.
TI Effect of the Leptin Receptor Q223R Polymorphism on the Host
Transcriptome following Infection with Entamoeba histolytica (vol 81, pg
1460, 2013)
SO INFECTION AND IMMUNITY
LA English
DT Correction
C1 [Mackey-Lawrence, Nicole M.] Univ Virginia, Sch Med, Dept Med, Div Infect Dis & Int Hlth, Charlottesville, VA 22908 USA.
North Shore Long Isl Hlth Syst, Manhasset, NY USA.
NIAID, Rocky Mt Lab, Res Technol Sect, Genom Unit,NIH, Hamilton, MT 59840 USA.
NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA.
RP Mackey-Lawrence, NM (reprint author), Univ Virginia, Sch Med, Dept Med, Div Infect Dis & Int Hlth, Charlottesville, VA 22908 USA.
NR 1
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 0019-9567
EI 1098-5522
J9 INFECT IMMUN
JI Infect. Immun.
PD NOV
PY 2013
VL 81
IS 11
BP 4322
EP 4322
DI 10.1128/IAI.00689-13
PG 1
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 235LI
UT WOS:000325719900038
ER
PT J
AU Federovitch, CM
Jones, YZ
Tong, AH
Boone, C
Prinz, WA
Hampton, RY
AF Federovitch, Christine M.
Jones, Ying Z.
Tong, Amy H.
Boone, Charles
Prinz, William A.
Hampton, Randolph Y.
TI Genetic and Structural Analysis of Hmg2p-induced Endoplasmic Reticulum
Remodeling in Saccharomyces cerevisiae
SO JOURNAL OF BACTERIOLOGY
LA English
DT Article
ID HMG-COA REDUCTASE; 3-HYDROXY-3-METHYLGLUTARYL-COENZYME-A REDUCTASE;
PHOSPHATIDYLSERINE DECARBOXYLASE; STEROL BIOSYNTHESIS; DELETION MUTANTS;
YEAST; PROTEIN; CELLS; ER; DEGRADATION
AB The endoplasmic reticulum (ER) is highly plastic, and increased expression of distinct single ER-resident membrane proteins, such as HMG-CoA reductase (HMGR), can induce a dramatic restructuring of ER membranes into highly organized arrays. Studies on the ER-remodeling behavior of the two yeast HMGR isozymes, Hmg1p and Hmg2p, suggest that they could be mechanistically distinct. We examined the features of Hmg2p required to generate its characteristic structures, and we found that the molecular requirements are similar to those of Hmg1p. However, the structures generated by Hmg1p and Hmg2p have distinct cell biological features determined by the transmembrane regions of the proteins. In parallel, we conducted a genetic screen to identify HER genes (required for Hmg2p-induced ER Remodeling), further confirming that the mechanisms of membrane reorganization by these two proteins are distinct because most of the HER genes were required for Hmg2p but not Hmg1p-induced ER remodeling. One of the HER genes identified was PSD1, which encodes the phospholipid biosynthetic enzyme phosphatidylserine decarboxylase. This direct connection to phospholipid biosynthesis prompted a more detailed examination of the effects of Hmg2p on phospholipid mutants and composition. Our analysis revealed that overexpression of Hmg2p caused significant and specific growth defects in nulls of the methylation pathway for phosphatidylcholine biosynthesis that includes the Psd1p enzyme. Furthermore, increased expression of Hmg2p altered the composition of cellular phospholipids in a manner that implied a role for PSD1. These phospholipid effects, unlike Hmg2p-induced ER remodeling, required the enzymatic activity of Hmg2p. Together, our results indicate that, although related, Hmg2p- and Hmg1p-induced ER remodeling are mechanistically distinct.
C1 [Federovitch, Christine M.; Hampton, Randolph Y.] Univ Calif San Diego, UCSD Div Biol Sci, Sect Cell & Dev Biol, La Jolla, CA 92093 USA.
[Jones, Ying Z.] Univ Calif San Diego, Natl Ctr Microscopy & Imaging Res, Dept Neurosci, La Jolla, CA 92093 USA.
[Jones, Ying Z.] Univ Toronto, Banting & Best Dept Med Res, Toronto, ON M5G 1L6, Canada.
[Prinz, William A.] NIDDK, Lab Cell Biochem & Biol, NIH, US Dept HHS, Bethesda, MD 20892 USA.
RP Hampton, RY (reprint author), Univ Calif San Diego, UCSD Div Biol Sci, Sect Cell & Dev Biol, La Jolla, CA 92093 USA.
EM rhampton@ucsd.edu
FU National Institutes of Health [5 R01 DK051996-15]; National Institutes
of Health genetic training [5T32GM008666]
FX We thank Scott Emr for use of the DeltaVision microscope, Gentry Patrick
for use of the Leica DM6000 microscope, and National Center for
Microscopy and Imaging Research at UCSD for use of the JEOL 1200
microscope. Plasmid pIU2589 was a kind gift from Martin Bard (Indiana
University-Purdue University Indianapolis, Indianapolis, IN). Mark Rose
(Princeton University, Princeton, NJ) provided anti-Kar2p antibody. We
thank Dennis Voelker (University of Colorado Health Sciences Center,
Denver, CO) for insightful discussions and the rescue plasmid
YCp50-PSD1. CMF wishes to thank Matthew Kinseth, Alicia Bicknell,
Danielle Huffman, and Renee Garza for many scientific discussions
regarding this work. RYH wishes to thank the Hampton laboratory for
patience, flexibility, and independent spirit during the past
(sabbatical) year. These studies were supported by National Institutes
of Health grant 5 R01 DK051996-15 (to R.Y.H.). C.M.F. was a trainee
under the National Institutes of Health genetic training grant
5T32GM008666.
NR 50
TC 0
Z9 0
U1 1
U2 9
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0021-9193
EI 1098-5530
J9 J BACTERIOL
JI J. Bacteriol.
PD NOV
PY 2013
VL 195
IS 21
BP 4506
EP 4520
DI 10.1091/mbc.E07-11-1188
PG 15
WC Microbiology
SC Microbiology
GA 235XI
UT WOS:000325755400007
ER
PT J
AU Han, H
Noureddin, M
Witthaus, M
Park, YJ
Hoofnagle, JH
Liang, TJ
Rotman, Y
AF Han, Hwalih
Noureddin, Mazen
Witthaus, Michael
Park, Yoon J.
Hoofnagle, Jay H.
Liang, T. Jake
Rotman, Yaron
TI Temperature rise after peginterferon alfa-2a injection in patients with
chronic hepatitis C is associated with virological response and is
modulated by IL28B genotype
SO JOURNAL OF HEPATOLOGY
LA English
DT Article
DE Fever; Temperature; Interferon alfa; IL28B; Hepatitis C; Treatment
ID RIBAVIRIN COMBINATION THERAPY; PLUS RIBAVIRIN; GENETIC-VARIATION;
IMMUNE-RESPONSE; VIRUS-INFECTION; INTERFERON; CLEARANCE; FEVER; UPDATE
AB Background & Aims: Interferon treatment for chronic hepatitis C is associated with non-specific symptoms including fever. We aimed to determine the association of temperature changes with interferon antiviral activity.
Methods: 60 treatment-naive patients with chronic hepatitis C (67% genotype 1/4/6, 33% genotype 2/3) were admitted to start peginterferon alfa-2a and ribavirin in a clinical trial. Temperature was measured at baseline and 3 times daily for the first 24 h and the maximal increase from baseline during that time (Delta T-max) was determined. Serum HCV-RNA, interferon-gamma-inducible protein-10 (IP-10) and expression of interferon-stimulated genes (ISGs - CD274, ISG15, RSAD2, IRF7, CXCL10) in peripheral blood mononuclear cells (PBMCs) were measured at very early time points, and response kinetics calculated. The IL28B single nucleotide polymorphism, rs12979860, was genotyped.
Results: Temperatures rose by 1.2 +/- 0.8 degrees C, peaking after 12.5 h. Delta T-max was strongly associated with 1st phase virological decline (r = 0.59, p < 0.0001) and was independent of gender, cirrhosis, viral genotype or baseline HCV-RNA. The association with 1st phase decline was seen in patients with rs12989760CC genotype (r = 0.65, p < 0.0001) but not in CC/CT (r = 0.13, p = 0.53) and patients with CC genotype had a higher Delta T-max (1.4 +/- 0.8 degrees C vs. 0.8 +/- 0.6 degrees C, p = 0.001). Delta T-max was associated with 6- and 24-h induction of serum IP-10 and of PBMC ISG expression, but only in patients with rs12989760CC. Delta T-max weakly predicted early virological response (AUC = 0.68, CI 0.49-0.88).
Conclusions: Temperature rise following peginterferon injection is closely associated with virological response and is modulated by IL28B polymorphism, reflecting host interferon-responsiveness. Published by Elsevier B.V. on behalf of the European Association for the Study of the Liver.
C1 [Han, Hwalih; Noureddin, Mazen; Witthaus, Michael; Park, Yoon J.; Hoofnagle, Jay H.; Liang, T. Jake; Rotman, Yaron] NIDDK, Liver Dis Branch, NIH, Bethesda, MD 20892 USA.
RP Rotman, Y (reprint author), NIDDK, Liver Dis Branch, NIH, 10 Ctr Dr,Bldg 10,Room 9C434,MSC 1800, Bethesda, MD 20892 USA.
EM rotmany@mail.nih.gov
OI Rotman, Yaron/0000-0002-7549-8216
FU intramural research program of NIDDK
FX This work was supported by the intramural research program of NIDDK.
NR 30
TC 3
Z9 3
U1 0
U2 3
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 2013
VL 59
IS 5
BP 957
EP 963
DI 10.1016/j.jhep.2013.07.004
PG 7
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 235WZ
UT WOS:000325754200009
PM 23850879
ER
PT J
AU Kapanadze, T
Gamrekelashvili, J
Ma, C
Chan, C
Zhao, F
Hewitt, S
Zender, L
Kapoor, V
Felsher, DW
Manns, MP
Korangy, F
Greten, TF
AF Kapanadze, Tamar
Gamrekelashvili, Jaba
Ma, Chi
Chan, Carmen
Zhao, Fei
Hewitt, Stephen
Zender, Lars
Kapoor, Veena
Felsher, Dean W.
Manns, Michael P.
Korangy, Firouzeh
Greten, Tim F.
TI Regulation of accumulation and function of myeloid derived suppressor
cells in different murine models of hepatocellular carcinoma
SO JOURNAL OF HEPATOLOGY
LA English
DT Article
DE Tumor immunology; Immunotherapy; Cancer vaccine
ID COLONY-STIMULATING FACTOR; TUMOR-BEARING MICE; DENDRITIC CELLS;
LIVER-CANCER; T-CELLS; SUBPOPULATIONS; INFLAMMATION; POPULATIONS;
PROGRESSION; IMMUNITY
AB Background & Aims: Myeloid derived suppressor cells (MDSC) are immature myeloid cells with immunosuppressive activity. They accumulate in tumor-bearing mice and humans with different types of cancer, including hepatocellular carcinoma (HCC). The aim of this study was to examine the biology of MDSC in murine HCC models and to identify a model, which mimics the human disease.
Methods: The comparative analysis of MDSC was performed in mice, bearing transplantable, diethylnitrosoamine (DEN)-induced and MYC-expressing HCC at different ages.
Results: An accumulation of MDSC was found in mice with HCC irrespective of the model tested. Transplantable tumors rapidly induced systemic recruitment of MDSC, in contrast to slow-growing DEN-induced or MYC-expressing HCC, where MDSC numbers only increased intra-hepatically in mice with advanced tumors. MDSC derived from mice with subcutaneous tumors were more suppressive than those from mice with DEN-induced HCC. Enhanced expression of genes associated with MDSC generation (GM-CSF, VEGF, IL6, IL1 beta) and migration (MCP-1, KC, S100A8, S100A9) was observed in mice with subcutaneous tumors. In contrast, only KC levels increased in mice with DEN-induced HCC. Both KC and GM-CSF overexpression or anti-KC and anti-GM-CSF treatment controlled MDSC frequency in mice with HCC. Finally, the frequency of MDSC decreased upon successful anti-tumor treatment with sorafenib.
Conclusions: Our data indicate that MDSC accumulation is a late event during hepatocarcinogenesis and differs significantly depending on the tumor model studied. Published by Elsevier B.V. on behalf of the European Association for the Study of the Liver.
C1 [Kapanadze, Tamar; Gamrekelashvili, Jaba; Ma, Chi; Chan, Carmen; Zhao, Fei; Korangy, Firouzeh; Greten, Tim F.] NCI, Gastrointestinal Malignancy Sect, Med Oncol Branch, Bethesda, MD 20892 USA.
[Kapanadze, Tamar; Gamrekelashvili, Jaba; Manns, Michael P.] Hannover Med Sch, Dept Gastroenterol Hepatol & Endocrinol, Hannover, Germany.
[Hewitt, Stephen] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA.
[Zender, Lars] Univ Tubingen, Dept Gastroenterol, Tubingen, Germany.
[Kapoor, Veena] NIH, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA.
[Felsher, Dean W.] Stanford Univ, Div Med Oncol, Dept Med, Stanford, CA 94305 USA.
RP Korangy, F (reprint author), NCI, NIH, CCR Bldg 10,Rm 12N226,9000 Rockville Pike, Bethesda, MD 20892 USA.
EM tim.greten@nih.gov
RI Greten, Tim/B-3127-2015;
OI Greten, Tim/0000-0002-0806-2535; Hewitt, Stephen/0000-0001-8283-1788
FU Intramural Research Program of the NIH; National Cancer Institute,
Center for Cancer Research; Networking Fund of the Helmholtz Association
within the Helmholtz Alliance on Immunotherapy of Cancer
FX The research was supported (in part) by the Intramural Research Program
of the NIH, National Cancer Institute, Center for Cancer Research and by
the Networking Fund of the Helmholtz Association within the Helmholtz
Alliance on Immunotherapy of Cancer to MPM.
NR 41
TC 37
Z9 38
U1 2
U2 19
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 2013
VL 59
IS 5
BP 1007
EP 1013
PG 7
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 235WZ
UT WOS:000325754200016
PM 23796475
ER
PT J
AU Miyagawa, F
Okiyama, N
Villarroel, V
Katz, SI
AF Miyagawa, Fumi
Okiyama, Naoko
Villarroel, Vadim
Katz, Stephen I.
TI Identification of CD3(+)CD4(-)CD8(-) T Cells as Potential Regulatory
Cells in an Experimental Murine Model of Graft-Versus-Host Skin Disease
(GVHD)
SO JOURNAL OF INVESTIGATIVE DERMATOLOGY
LA English
DT Article
ID CARDIAC XENOGRAFT SURVIVAL; RECEPTOR TRANSGENIC MICE; NONOBESE DIABETIC
MICE; CLONAL ELIMINATION; IMMUNE-RESPONSES; MOUSE MODEL; ANTIGEN;
TOLERANCE; DIFFERENTIATION; PEPTIDE
AB We have developed K14-mOVA transgenic (Tg) mice that express membrane-associated ovalbumin (mOVA) under the control of a K14 promoter, as well as double Tg mice, by crossing them with OT-I mice that have a TCR recognizing the OVA peptide. When injected with CD8(+) OT-I cells, K14-mOVA Tg mice develop graft-versus-host disease (GVHD), whereas double Tg mice are protected. This suggests that, in double Tg mice, regulatory mechanisms may prevent infused OT-I cells from inducing GVHD. We demonstrated that, after adoptive transfer, TCR alpha beta(+)CD3(+)CD4(-)CD8(-)NK1.1(-) double-negative (DN) T cells are increased in the peripheral lymphoid organs and skin of double Tg mice and exhibit a V alpha 2(+)V beta 5(+)TCR that has the same TCR specificity as OT-I cells. These DN T cells isolated from tolerant double Tg mice proliferated in response to OVA peptide and produced IFN-gamma in the presence of IL-2. These cells could also suppress the proliferation of OT-I cells and were able to specifically kill activated OT-I cells through Fas/Fas ligand interaction. These findings suggest that DN T cells that accumulate in double Tg mice have regulatory functions and may have a role in the maintenance of peripheral tolerance in vivo.
C1 [Miyagawa, Fumi; Okiyama, Naoko; Villarroel, Vadim; Katz, Stephen I.] NCI, Dermatol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Katz, SI (reprint author), NCI, Dermatol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM katzs@od.niams.nih.gov
FU Intramural NIH HHS [ZIA SC003657-38]
NR 36
TC 6
Z9 7
U1 0
U2 3
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0022-202X
EI 1523-1747
J9 J INVEST DERMATOL
JI J. Invest. Dermatol.
PD NOV
PY 2013
VL 133
IS 11
BP 2538
EP 2545
DI 10.1038/jid.2013.212
PG 8
WC Dermatology
SC Dermatology
GA 236OM
UT WOS:000325807800010
PM 23648548
ER
PT J
AU Odia, Y
Orr, BA
Bell, WR
Eberhart, CG
Rodriguez, FJ
AF Odia, Yazmin
Orr, Brent A.
Bell, W. Robert
Eberhart, Charles G.
Rodriguez, Fausto J.
TI cMYC expression in infiltrating gliomas: associations with IDH1
mutations, clinicopathologic features and outcome
SO JOURNAL OF NEURO-ONCOLOGY
LA English
DT Article
DE cMYC; IDH1; IDH1 (R132H); Gliomas; Glioblastoma; Astrocytoma; Prognosis;
Survival
ID CENTRAL-NERVOUS-SYSTEM; C-MYC AMPLIFICATION; ASTROCYTIC TUMORS;
STEM-CELLS; GLIOBLASTOMA; MEDULLOBLASTOMA; CLASSIFICATION; METABOLISM;
TELOMERES; GROWTH
AB Gliomas are among the most frequent adult primary brain tumors. Mutations in IDH1, a metabolic enzyme, strongly correlate with secondary glioblastomas and increased survival. cMYC is an oncogene also implicated in aberrant metabolism, but its prognostic impact remains unclear. Recent genotyping studies also showed SNP variants near the cMYC gene locus, associate with an increased risk for development of IDH1/2 mutant gliomas suggesting a possible interaction between cMYC and IDH1. We evaluated nuclear cMYC protein levels and IDH1 (R132H) by immunohistochemistry in patients with oligodendroglioma/oligoastrocytomas (n = 20), astrocytomas (grade II) (n = 19), anaplastic astrocytomas (n = 21) or glioblastomas (n = 111). Of 158 tumors with sufficient tissue, 110 (70 %) showed nuclear cMYC immunopositivity-most frequent (95 %, chi(2) p = 0.0248) and intense (mean 1.33, ANOVA p = 0.0179) in anaplastic astrocytomas versus glioblastomas (63 %) or low grade gliomas (74 %). cMYC expression associated with younger age as well as p53 immunopositivity (OR = 3.6, p = 0.0332) and mutant IDH1 (R132H) (OR = 7.4, p = 0.06) among malignant gliomas in our cohort. Independent analysis of the publically available TCGA glioblastoma dataset confirmed our strong association between cMYC and mutant IDH1 expression. Both IDH1 (R132H) and cMYC protein expression were associated with improved overall survival by univariate analysis. However, cMYC co-expression associated with shortened time to malignant transformation and overall survival among IDH1 (R132H) mutants in both univariate and multivariate analyses. In summary, our findings suggest that cMYC may be associated with a unique clinicopathologic and biologic group of infiltrating gliomas and help mediate the malignant transformation of IDH1 mutant gliomas.
C1 [Odia, Yazmin] Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA.
[Odia, Yazmin] NCI, Neurooncol Branch, Bethesda, MD 20892 USA.
[Orr, Brent A.; Bell, W. Robert; Eberhart, Charles G.; Rodriguez, Fausto J.] Johns Hopkins Univ, Sch Med, Dept Pathol, Div Neuropathol,Johns Hopkins Hosp, Baltimore, MD 21205 USA.
[Orr, Brent A.] St Jude Childrens Res Hosp, Dept Pathol, Memphis, TN 38105 USA.
[Eberhart, Charles G.; Rodriguez, Fausto J.] Johns Hopkins Univ, Sch Med, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21205 USA.
RP Rodriguez, FJ (reprint author), Johns Hopkins Univ, Sch Med, Dept Pathol, Div Neuropathol,Johns Hopkins Hosp, Sheikh Zayed Tower,Room M2101,1800 Orleans St, Baltimore, MD 21205 USA.
EM frodrig4@jhmi.edu
FU National Institute of Neurological Disorders and Stroke (NINDS) [NINDS
5R25NS065729-02]; Children's Cancer Foundation, Inc. [5R01NS055089];
James S. McDonnell Foundation
FX Grant funding provided in part by the National Institute of Neurological
Disorders and Stroke (NINDS) Research Education Program for Residents
and Fellows in Neurology and Neurosurgery (2009-10)-Primary Investigator
Argye Hillis, MD MS, Johns Hopkins Hospital, Baltimore, MD [NINDS
5R25NS065729-02] (YO); Children's Cancer Foundation, Inc. (CGE, FJR),
5R01NS055089 (CGE), and James S. McDonnell Foundation (CGE). Jessica
Hicks performed all cMYC immunohistochemistry on glioma specimens. The
authors also thank the Mayo Clinic cytogenetic shared resource for
technical assistance.
NR 44
TC 4
Z9 5
U1 0
U2 8
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 2013
VL 115
IS 2
BP 249
EP 259
DI 10.1007/s11060-013-1221-4
PG 11
WC Oncology; Clinical Neurology
SC Oncology; Neurosciences & Neurology
GA 236TJ
UT WOS:000325821900014
PM 23934175
ER
PT J
AU Derdeyn, CP
Fiorella, D
Lynn, MJ
Barnwell, SL
Zaidat, OO
Meyers, PM
Gobin, YP
Dion, J
Lane, BF
Turan, TN
Janis, LS
Chimowitz, MI
AF Derdeyn, Colin P.
Fiorella, David
Lynn, Michael J.
Barnwell, Stanley L.
Zaidat, Osama O.
Meyers, Philip M.
Gobin, Y. Pierre
Dion, Jacques
Lane, Bethany F.
Turan, Tanya N.
Janis, L. Scott
Chimowitz, Marc I.
CA SAMMPRIS Trial Investigators
TI Impact of operator and site experience on outcomes after angioplasty and
stenting in the SAMMPRIS trial
SO JOURNAL OF NEUROINTERVENTIONAL SURGERY
LA English
DT Article
DE Stroke; Stent; Angioplasty
ID INTRACRANIAL ARTERIAL-STENOSIS; AGGRESSIVE MEDICAL-MANAGEMENT;
PREVENTING RECURRENT STROKE; ATHEROSCLEROTIC-DISEASE; WINGSPAN STENT;
THERAPY; DESIGN
AB Background and purpose To investigate the relationship between physician and site experience and the risk of 30 day hemorrhagic and ischemic strokes in the stenting arm of the Stenting and Aggressive Medical Management for the Prevention of Recurrent Ischemic Stroke (SAMMPRIS) trial.
Methods Study records and an investigator survey were examined for physician and site related factors, including: number of Wingspan and aneurysm stents submitted for credentialing, number of study procedures performed in SAMMPRIS, years in practice after training, primary specialty, and site enrollment. Bivariate and multivariate analyses were performed to determine if these factors were associated with the 30 day rate of cerebrovascular events after angioplasty and stenting.
Results 213 patients underwent angioplasty alone (n=5) or angioplasty and stenting (n=208) with study devices by 63 interventionists at 48 sites. For credentialing, the median number of Wingspan and similar aneurysm stent cases submitted by study interventionists were 10 and 6, respectively. Interventionists with higher numbers (>10) of Wingspan cases submitted for credentialing tended to have higher rates of 30 day events (19.0% vs 9.9%) than those with <10 cases. High enrolling sites in the trial tended to have lower rates of hemorrhagic stroke (9.8% at sites enrolling <12 patients vs 2.7% at sites enrolling >12 patients).
Conclusions Interventionists credentialed with less Wingspan experience were not responsible for the high rate of periprocedural stroke in SAMMPRIS. Hemorrhagic stroke may be related to low enrollment in the trial but not previous Wingspan experience.
C1 [Derdeyn, Colin P.] Washington Univ, Sch Med, Mallinckrodt Inst Radiol, St Louis, MO 63130 USA.
[Derdeyn, Colin P.] Washington Univ, Sch Med, Mallinckrodt Inst Radiol, St Louis, MO USA.
[Derdeyn, Colin P.] Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA.
[Derdeyn, Colin P.] Washington Univ, Sch Med, Dept Neurosurg, St Louis, MO USA.
[Fiorella, David] SUNY Stony Brook, Dept Neurosurg, Stony Brook, NY USA.
[Lynn, Michael J.; Lane, Bethany F.] Emory Univ, Rollins Sch Publ Hlth, Dept Biostat & Bioinformat, Atlanta, GA 30322 USA.
[Barnwell, Stanley L.] Oregon Hlth & Sci Univ, Dept Neurol Surg, Portland, OR USA.
[Barnwell, Stanley L.] Oregon Hlth & Sci Univ, Dotter Intervent Inst, Portland, OR USA.
[Zaidat, Osama O.] Med Coll Wisconsin, Dept Neurol, Milwaukee, WI 53226 USA.
[Zaidat, Osama O.] Med Coll Wisconsin, Dept Radiol, Milwaukee, WI 53226 USA.
[Zaidat, Osama O.] Med Coll Wisconsin, Dept Neurosurg, Milwaukee, WI 53226 USA.
[Meyers, Philip M.] Columbia Univ, Dept Radiol, New York, NY USA.
[Gobin, Y. Pierre] Cornell Univ, Dept Radiol, New York, NY 10021 USA.
[Dion, Jacques] Emory Univ, Dept Radiol & Neurosurg, Atlanta, GA 30322 USA.
[Turan, Tanya N.; Chimowitz, Marc I.] Med Univ S Carolina, Dept Neurosci, Charleston, SC 29425 USA.
[Janis, L. Scott] NINDS, NIH, Bethesda, MD 20892 USA.
RP Derdeyn, CP (reprint author), Washington Univ, Sch Med, Mallinckrodt Inst Radiol, St Louis, MO 63130 USA.
EM derdeync@mir.wustl.edu
OI Turan, Tanya/0000-0001-5399-8845; Derdeyn, Colin/0000-0002-5932-2683
FU US Public Health Service National Institute of Neurological Disorders
and Stroke (NINDS) [U01 NS058728]; National Institutes of Health;
Medical University of South Carolina [UL1RR029882]; University of
Florida [UL1RR029889]; University of Cincinnati [UL1RR029890];
University of California, San Francisco [UL1RR024131]; Stryker
Neurovascular
FX The SAMMPRIS trial was funded by a research grant (U01 NS058728) from
the US Public Health Service National Institute of Neurological
Disorders and Stroke (NINDS). In addition, the following Clinical and
Translational Science Awards, funded by the National Institutes of
Health, provided local support for the evaluation of patients in the
trial: Medical University of South Carolina (UL1RR029882), University of
Florida (UL1RR029889), University of Cincinnati (UL1RR029890), and
University of California, San Francisco (UL1RR024131). Stryker
Neurovascular (formerly Boston Scientific Neurovascular) provided study
devices and supplemental funding for third party device distribution,
site monitoring, and study auditing.
NR 13
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Z9 20
U1 0
U2 5
PU BMJ PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 1759-8478
EI 1759-8486
J9 J NEUROINTERV SURG
JI J. NeuroInterventional Surg.
PD NOV
PY 2013
VL 5
IS 6
BP 528
EP 533
DI 10.1136/neurintsurg-2012-010504
PG 6
WC Neuroimaging; Surgery
SC Neurosciences & Neurology; Surgery
GA 232JT
UT WOS:000325490700020
PM 22977278
ER
PT J
AU Rais-Bahrami, S
Siddiqui, MM
Turkbey, B
Stamatakis, L
Logan, J
Hoang, AN
Walton-Diaz, A
Vourganti, S
Truong, H
Kruecker, J
Merino, MJ
Wood, BJ
Choyke, PL
Pinto, PA
AF Rais-Bahrami, Soroush
Siddiqui, M. Minhaj
Turkbey, Baris
Stamatakis, Lambros
Logan, Jennifer
Hoang, Anthony N.
Walton-Diaz, Annerleim
Vourganti, Srinivas
Truong, Hong
Kruecker, Jochen
Merino, Maria J.
Wood, Bradford J.
Choyke, Peter L.
Pinto, Peter A.
TI Utility of Multiparametric Magnetic Resonance Imaging Suspicion Levels
for Detecting Prostate Cancer
SO JOURNAL OF UROLOGY
LA English
DT Article
DE neoplasm grading; magnetic resonance imaging; digital rectal
examination; prostate; biopsy
ID ACTIVE SURVEILLANCE; ULTRASOUND FUSION; TUMOR VOLUME; BIOPSY; SPECIMENS;
MRI
AB Purpose: We determine the usefulness of multiparametric magnetic resonance imaging in detecting prostate cancer, with a specific focus on detecting higher grade prostate cancer.
Materials and Methods: Prospectively 583 patients who underwent multiparametric magnetic resonance imaging and subsequent prostate biopsy at a single institution were evaluated. On multiparametric magnetic resonance imaging, lesions were identified and scored as low, moderate or high suspicion for prostate cancer based on a validated scoring system. Magnetic resonance/ultra-sound fusion guided biopsies of magnetic resonance imaging lesions in addition to systematic 12-core biopsies were performed. Correlations between the highest assigned multiparametric magnetic resonance imaging suspicion score and presence of cancer and biopsy Gleason score on the first fusion biopsy session were assessed using univariate and multivariate logistic regression models. Sensitivity, specificity, negative predictive value and positive predictive value were calculated and ROC curves were developed to assess the discriminative ability of multiparametric magnetic resonance imaging as a diagnostic tool for various biopsy Gleason score cohorts.
Results: Significant correlations were found between age, prostate specific antigen, prostate volume, and multiparametric magnetic resonance imaging suspicion score and the presence of prostate cancer (p < 0.0001). On multivariate analyses controlling for age, prostate specific antigen and prostate volume, increasing multiparametric magnetic resonance imaging suspicion was an independent prognosticator of prostate cancer detection (OR 2.2, p < 0.0001). Also, incremental increases in multiparametric magnetic resonance imaging suspicion score demonstrated stronger associations with cancer detection in patients with Gleason 7 or greater (OR 3.3, p < 0.001) and Gleason 8 or greater (OR 4.2, p < 0.0001) prostate cancer. Assessing multiparametric magnetic resonance imaging as a diagnostic tool for all prostate cancer, biopsy Gleason score 7 or greater, and biopsy Gleason score 8 or greater separately via ROC analyses demonstrated increasing accuracy of multiparametric magnetic resonance imaging for higher grade disease (AUC 0.64, 0.69, and 0.72, respectively).
Conclusions: Multiparametric magnetic resonance imaging is a clinically useful modality to detect and characterize prostate cancer, particularly in men with higher grade disease.
C1 [Rais-Bahrami, Soroush; Siddiqui, M. Minhaj; Stamatakis, Lambros; Logan, Jennifer; Hoang, Anthony N.; Walton-Diaz, Annerleim; Vourganti, Srinivas; Truong, Hong; Pinto, Peter A.] NCI, Urol Oncol Branch, Bethesda, MD 20892 USA.
[Turkbey, Baris; Choyke, Peter L.] NCI, Mol Imaging Program, Bethesda, MD 20892 USA.
[Merino, Maria J.] NCI, Pathol Lab, Bethesda, MD 20892 USA.
[Kruecker, Jochen; Wood, Bradford J.; Pinto, Peter A.] Natl Canc Inst & Clin Ctr, Ctr Intervent Oncol, NIH, Bethesda, MD USA.
[Kruecker, Jochen] Philips Res North America, Briarcliff Manor, NY USA.
RP Pinto, PA (reprint author), NCI, Urol Oncol Branch, Bethesda, MD 20892 USA.
OI Siddiqui, Mohummad/0000-0002-4484-6820; Rais-Bahrami,
Soroush/0000-0001-9466-9925
FU Intramural Research Program of the National Institutes of Health,
National Cancer Institute, Center for Cancer Research
FX Supported by the Intramural Research Program of the National Institutes
of Health, National Cancer Institute, Center for Cancer Research. NIH
and Philips Healthcare have a cooperative research and development
agreement. NIH and Philips share intellectual property in the field.
NR 26
TC 78
Z9 79
U1 2
U2 15
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-5347
EI 1527-3792
J9 J UROLOGY
JI J. Urol.
PD NOV
PY 2013
VL 190
IS 5
BP 1721
EP 1727
DI 10.1016/j.juro.2013.05.052
PG 7
WC Urology & Nephrology
SC Urology & Nephrology
GA 232DV
UT WOS:000325471400030
PM 23727310
ER
PT J
AU Hourigan, CS
Forde, PM
Ambinder, RF
Gladstone, DE
AF Hourigan, Christopher S.
Forde, Patrick M.
Ambinder, Richard F.
Gladstone, Douglas E.
TI Bortezomib salvage therapy in refractory acute adult T-cell
leukemia/lymphoma
SO LEUKEMIA & LYMPHOMA
LA English
DT Letter
ID PROTEASOME INHIBITOR; TRANSPLANTATION; LYMPHOMA; EXPERIENCE; EFFICACY;
SUBTYPES; ATL
C1 [Hourigan, Christopher S.] NHLBI, Myeloid Malignancies Sect, Bethesda, MD 20892 USA.
[Hourigan, Christopher S.; Forde, Patrick M.; Ambinder, Richard F.; Gladstone, Douglas E.] Johns Hopkins Univ Hosp, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21287 USA.
RP Hourigan, CS (reprint author), NHLBI, Myeloid Malignancies Sect, Room 6C-103C,10 Ctr Dr, Bethesda, MD 20892 USA.
EM hourigan@nih.gov
RI Hourigan, Christopher/S-2476-2016
OI Hourigan, Christopher/0000-0002-6189-8067
FU Intramural NIH HHS [ZIA HL006163-01]; NCI NIH HHS [P30 CA006973]
NR 14
TC 2
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U1 0
U2 1
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1042-8194
EI 1029-2403
J9 LEUKEMIA LYMPHOMA
JI Leuk. Lymphoma
PD NOV
PY 2013
VL 54
IS 11
BP 2563
EP 2564
DI 10.3109/10428194.2013.780289
PG 2
WC Oncology; Hematology
SC Oncology; Hematology
GA 232MV
UT WOS:000325498900043
PM 23445368
ER
PT J
AU Coussens, NP
Hayashi, R
Brown, PH
Balagopalan, L
Balbo, A
Akpan, I
Houtman, JCD
Barr, VA
Schuck, P
Appella, E
Samelson, LE
AF Coussens, Nathan P.
Hayashi, Ryo
Brown, Patrick H.
Balagopalan, Lakshmi
Balbo, Andrea
Akpan, Itoro
Houtman, Jon C. D.
Barr, Valarie A.
Schuck, Peter
Appella, Ettore
Samelson, Lawrence E.
TI Multipoint Binding of the SLP-76 SH2 Domain to ADAP Is Critical for
Oligomerization of SLP-76 Signaling Complexes in Stimulated T Cells
SO MOLECULAR AND CELLULAR BIOLOGY
LA English
DT Article
ID ANTIGEN RECEPTOR; GRB2-SH2 DOMAIN; COOPERATIVE INTERACTIONS;
PHOSPHOLIPASE C-GAMMA-1; PROTEIN INTERACTIONS; TYROSINE KINASES;
HIGH-AFFINITY; ACTIVATION; MICROCLUSTERS; ACTIN
AB The adapter molecules SLP-76 and LAT play central roles in T cell activation by recruiting enzymes and other adapters into multiprotein complexes that coordinate highly regulated signal transduction pathways. While many of the associated proteins have been characterized, less is known concerning the mechanisms of assembly for these dynamic and potentially heterogeneous signaling complexes. Following T cell receptor (TCR) stimulation, SLP-76 is found in structures called microclusters, which contain many signaling complexes. Previous studies showed that a mutation to the SLP-76 C-terminal SH2 domain nearly abolished SLP-76 microclusters, suggesting that the SH2 domain facilitates incorporation of signaling complexes into microclusters. S. C. Bunnell, A. L. Singer, D. I. Hong, B. H. Jacque, M. S. Jordan, M. C. Seminario, V. A. Barr, G. A. Koretzky, and L. E. Samelson, Mol. Cell. Biol., 26: 7155-7166, 2006). Using biophysical methods, we demonstrate that the adapter, ADAP, contains three binding sites for SLP-76, and that multipoint binding to ADAP fragments oligomerizes the SLP-76 SH2 domain in vitro. These results were complemented with confocal imaging and functional studies of cells expressing ADAP with various mutations. Our results demonstrate that all three binding sites are critical for SLP-76 microcluster assembly, but any combination of two sites will partially induce microclusters. These data support a model whereby multipoint binding of SLP-76 to ADAP facilitates the assembly of SLP-76 microclusters. This model has implications for the regulation of SLP-76 and LAT microclusters and, as a result, T cell signaling.
C1 [Coussens, Nathan P.; Balagopalan, Lakshmi; Akpan, Itoro; Houtman, Jon C. D.; Barr, Valarie A.; Samelson, Lawrence E.] NCI, Cellular & Mol Biol Lab, Bethesda, MD 20892 USA.
[Hayashi, Ryo; Appella, Ettore] NCI, Cell Biol Lab, Bethesda, MD 20892 USA.
[Brown, Patrick H.; Balbo, Andrea] Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD USA.
[Schuck, Peter] Natl Inst Biomed Imaging & Bioengn, Dynam Macromol Assembly Sect, NIH, Bethesda, MD USA.
RP Samelson, LE (reprint author), NCI, Cellular & Mol Biol Lab, Bldg 37, Bethesda, MD 20892 USA.
EM samelsonl@helix.nih.gov
OI Schuck, Peter/0000-0002-8859-6966; Houtman, Jon/0000-0002-5307-9854
FU Intramural Research Programs of the Center for Cancer Research; NCI;
NIBIB, National Institutes of Health
FX This research was supported by the Intramural Research Programs of the
Center for Cancer Research, NCI, and NIBIB, National Institutes of
Health.
NR 52
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U1 0
U2 0
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0270-7306
EI 1098-5549
J9 MOL CELL BIOL
JI Mol. Cell. Biol.
PD NOV
PY 2013
VL 33
IS 21
BP 4140
EP 4151
DI 10.1128/MCB.00410-13
PG 12
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 235XS
UT WOS:000325756800001
PM 23979596
ER
PT J
AU Gatch, MB
Kozlenkov, A
Huang, RQ
Yang, WJ
Nguyen, JD
Gonzalez-Maeso, J
Rice, KC
France, CP
Dillon, GH
Forster, MJ
Schetz, JA
AF Gatch, Michael B.
Kozlenkov, Alexey
Huang, Ren-Qi
Yang, Wenjuan
Nguyen, Jacques D.
Gonzalez-Maeso, Javier
Rice, Kenner C.
France, Charles P.
Dillon, Glenn H.
Forster, Michael J.
Schetz, John A.
TI The HIV Antiretroviral Drug Efavirenz has LSD-Like Properties
SO NEUROPSYCHOPHARMACOLOGY
LA English
DT Article
DE hallucinogen; adverse neuropsychiatric events; side effects; AIDS
ID MONOAMINE TRANSPORTER; DOPAMINE-RECEPTORS; 5-HT2C RECEPTORS; IN-VIVO;
HALLUCINOGENS; MICE; RATS; MECHANISM; INFECTION; PSYCHOSIS
AB Anecdotal reports have surfaced concerning misuse of the HIV antiretroviral medication efavirenz ((4S)-6-chloro-4-(2-cyclopropylethynyl)- 4-(trifluoromethyl)-2,4-dihydro-1H-3,1-benzoxazin-2-one) by HIV patients and non-infected teens who crush the pills and smoke the powder for its psychoactive effects. Molecular profiling of the receptor pharmacology of efavirenz pinpointed interactions with multiple established sites of action for other known drugs of abuse including catecholamine and indolamine transporters, and GABA(A) and 5-HT2A receptors. In rodents, interaction with the 5-HT2A receptor, a primary site of action of lysergic acid diethylamine (LSD), appears to dominate efavirenz's behavioral profile. Both LSD and efavirenz reduce ambulation in a novel open-field environment. Efavirenz occasions drug-lever responding in rats discriminating LSD from saline, and this effect is abolished by selective blockade of the 5-HT2A receptor. Similar to LSD, efavirenz induces head-twitch responses in wild-type, but not in 5-HT2A-knockout, mice. Despite having GABA(A)-potentiating effects (like benzodiazepines and barbiturates), and interactions with dopamine transporter, serotonin transporter, and vesicular monoamine transporter 2 (like cocaine and methamphetamine), efavirenz fails to maintain responding in rats that self-administer cocaine, and it fails to produce a conditioned place preference. Although its molecular pharmacology is multifarious, efavirenz's prevailing behavioral effect in rodents is consistent with LSD-like activity mediated via the 5-HT2A receptor. This finding correlates, in part, with the subjective experiences in humans who abuse efavirenz and with specific dose-dependent adverse neuropsychiatric events, such as hallucinations and night terrors, reported by HIV patients taking it as a medication.
C1 [Gatch, Michael B.; Huang, Ren-Qi; Nguyen, Jacques D.; Dillon, Glenn H.; Forster, Michael J.; Schetz, John A.] Univ N Texas, Dept Pharmacol & Neurosci, Hlth Sci Ctr, Ft Worth, TX 76107 USA.
[Kozlenkov, Alexey; Gonzalez-Maeso, Javier] Mt Sinai Sch Med, Dept Psychiat & Neurol, New York, NY USA.
[Yang, Wenjuan; France, Charles P.] Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol, San Antonio, TX 78229 USA.
[Rice, Kenner C.] NIDA, Drug Design & Synth Sect, Chem Biol Res Branch, Bethesda, MD 20892 USA.
[Rice, Kenner C.] NIAAA, NIH, Bethesda, MD USA.
[Dillon, Glenn H.; Forster, Michael J.; Schetz, John A.] Univ N Texas, Inst Aging & Alzheimers Dis Res, Hlth Sci Ctr, Ft Worth, TX USA.
[Schetz, John A.] Univ N Texas, Texas Coll Osteopath Med, Dept Psychiat, Hlth Sci Ctr, Ft Worth, TX 76107 USA.
[Schetz, John A.] Univ N Texas, Dept Hlth Management & Policy, Sch Publ Hlth, Hlth Sci Ctr, Ft Worth, TX USA.
RP Schetz, JA (reprint author), Univ N Texas, Dept Pharmacol & Neurosci, Hlth Sci Ctr, 3500 Camp Bowie Blvd, Ft Worth, TX 76107 USA.
EM John.Schetz@unthsc.edu
FU National Institutes of Health [R01-MH063162, K05DA17918, R01 MH084894,
R01-DA022370, N01DA-7-8872 (HHSN271200700014C)]; UNTHSC Intramural Grant
[RI-6015]; Intramural Research Programs of the National Institute on
Drug Abuse; National Institute on Alcohol Abuse and Alcoholism
FX We thank Dr Michael Oglesby for critical reading of early versions of
the manuscript, Dr Kathyrn Cunningham for insightful discussions related
to this work, and Brian Weiss, Shahnawaz Amdani, Marshayla McPhaul,
Terrell Holloway and Fatima Sahyouni for technical assistance. We also
thank Dr David Lynch (University of Pennsylvania) for providing the
cDNAs encoding rat NR1a, NR2A, and
NR2B, Dr Eldo Kuzhikandathil (UMDNJ-New Jersey Medical
School) for providing an Att20 cell line stably expressing the human D3
receptor, and Dr David B Bylund (University of Nebraska Medical Center)
for providing the HEK293 cell line stably expressing the human
alpha2C adrenergic receptor. This work was supported, in
part, by the National Institutes of Health (Grant R01-MH063162 (JAS);
K05DA17918 (CPF); R01 MH084894 (JGM); R01-DA022370 (GHD, MJF);
N01DA-7-8872 (HHSN271200700014C) (MJF)), UNTHSC Intramural Grant RI-6015
(JAS, MG, and MJF), and institutional funds (JAS, MJF, and GHD). A
portion of this work was also supported by the Intramural Research
Programs of the National Institute on Drug Abuse and the National
Institute on Alcohol Abuse and Alcoholism (KCR).
NR 43
TC 18
Z9 20
U1 1
U2 15
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0893-133X
EI 1740-634X
J9 NEUROPSYCHOPHARMACOL
JI Neuropsychopharmacology
PD NOV
PY 2013
VL 38
IS 12
BP 2373
EP 2384
DI 10.1038/npp.2013.135
PG 12
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 235IF
UT WOS:000325710200005
PM 23702798
ER
PT J
AU Iemolo, A
Blasio, A
St Cyr, SA
Jiang, F
Rice, KC
Sabino, V
Cottone, P
AF Iemolo, Attilio
Blasio, Angelo
St Cyr, Stephen A.
Jiang, Fanny
Rice, Kenner C.
Sabino, Valentina
Cottone, Pietro
TI CRF-CRF1 Receptor System in the Central and Basolateral Nuclei of the
Amygdala Differentially Mediates Excessive Eating of Palatable Food
SO NEUROPSYCHOPHARMACOLOGY
LA English
DT Article
DE corticotropin-releasing factor; BNST; addiction; anxiety; hypophagia
ID CORTICOTROPIN-RELEASING-FACTOR; DARK SIDE; DRUG-ADDICTION; INTERMITTENT
ACCESS; PREFERRED FOOD; DEPENDENT RATS; ANIMAL-MODELS; WITHDRAWAL;
STRESS; CRF
AB Highly palatable foods and dieting are major contributing factors for the development of compulsive eating in obesity and eating disorders. We previously demonstrated that intermittent access to palatable food results in corticotropin-releasing factor-1 (CRF1) receptor antagonist-reversible behaviors, which include excessive palatable food intake, hypophagia of regular chow, and anxiety-like behavior. However, the brain areas mediating these effects are still unknown. Male Wistar rats were either fed chow continuously for 7 days/week (Chow/Chow group), or fed chow intermittently 5 days/week, followed by a sucrose, palatable diet 2 days/week (Chow/Palatable group). Following chronic diet alternation, the effects of microinfusing the CRF1 receptor antagonist R121919 (0, 0.5, 1.5 mg/side) in the central nucleus of the amygdala (CeA), the basolateral nucleus of the amygdala (BlA), or the bed nucleus of the stria terminalis (BNST) were evaluated on excessive intake of the palatable diet, chow hypophagia, and anxiety-like behavior. Furthermore, CRF immunostaining was evaluated in the brain of diet cycled rats. Intra-CeA R121919 blocked both excessive palatable food intake and anxiety-like behavior in Chow/Palatable rats, without affecting chow hypophagia. Conversely, intra-BlA R121919 reduced the chow hypophagia in Chow/Palatable rats, without affecting excessive palatable food intake or anxiety-like behavior. Intra-BNST treatment had no effect. The treatments did not modify the behavior of Chow/Chow rats. Immunohistochemistry revealed an increased number of CRF-positive cells in CeA-but not in BlA or BNST-of Chow/Palatable rats, during both withdrawal and renewed access to the palatable diet, compared with controls. These results provide functional evidence that the CRF-CRF1 receptor system in CeA and BlA has a differential role in mediating maladaptive behaviors resulting from palatable diet cycling. Neuropsychopharmacology (2013)
C1 [Iemolo, Attilio; Blasio, Angelo; St Cyr, Stephen A.; Jiang, Fanny; Sabino, Valentina; Cottone, Pietro] Boston Univ, Sch Med, Dept Pharmacol, Lab Addict Disorders, Boston, MA 02118 USA.
[Iemolo, Attilio; Blasio, Angelo; St Cyr, Stephen A.; Jiang, Fanny; Sabino, Valentina; Cottone, Pietro] Boston Univ, Sch Med, Dept Psychiat, Lab Addict Disorders, Boston, MA 02118 USA.
[Rice, Kenner C.] NIDA, Chem Biol Res Branch, Rockville, MD USA.
[Rice, Kenner C.] NIAAA, Rockville, MD 20852 USA.
RP Cottone, P (reprint author), Boston Univ, Sch Med, Dept Pharmacol, Lab Addict Disorders, 72 East Concord St,R-618, Boston, MA 02118 USA.
EM cottone@bu.edu
RI Cottone, Pietro/F-5291-2012; Sabino, Valentina/F-5290-2012
OI Cottone, Pietro/0000-0003-1320-1672; Sabino,
Valentina/0000-0002-6680-1279
FU National Institute on Drug Abuse(NIDA) [DA023680, DA030425, MH091945,
MH093650, AA016731]; National Institute of Mental Health (NIMH);
National Institute on Alcohol Abuse and Alcoholism (NIAAA); Peter Paul
Career Development Professorship; Boston University's Undergraduate
Research Opportunities Program (UROP); NIH Intramural Research Programs
of the National Institute on Drug Abuse; National Institute of Alcohol
Abuse and Alcoholism, NIH, DHHS
FX We thank Duncan Momaney, Aditi R Narayan, Jina Kwak for technical
assistance, and Tamara Zeric for technical and editorial assistance. We
also thank Elena F Crawford for helpful suggestions related to CRF
immunohistochemistry. This publication was made possible by grant
numbers DA023680, DA030425, MH091945, MH093650, and AA016731, from the
National Institute on Drug Abuse(NIDA), the National Institute of Mental
Health (NIMH), and the National Institute on Alcohol Abuse and
Alcoholism (NIAAA), by the Peter Paul Career Development Professorship
(PC) and by Boston University's Undergraduate Research Opportunities
Program (UROP). This research was also supported by the NIH Intramural
Research Programs of the National Institute on Drug Abuse, and the
National Institute of Alcohol Abuse and Alcoholism, NIH, DHHS. Its
contents are solely the responsibility of the authors and do not
necessarily represent the official views of the National Institutes of
Health.
NR 49
TC 18
Z9 18
U1 0
U2 10
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0893-133X
EI 1740-634X
J9 NEUROPSYCHOPHARMACOL
JI Neuropsychopharmacology
PD NOV
PY 2013
VL 38
IS 12
BP 2456
EP 2466
DI 10.1038/npp.2013.147
PG 11
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 235IF
UT WOS:000325710200014
PM 23748225
ER
PT J
AU Blasio, A
Iemolo, A
Sabino, V
Petrosino, S
Steardo, L
Rice, KC
Orlando, P
Iannotti, FA
Di Marzo, V
Zorrilla, EP
Cottone, P
AF Blasio, Angelo
Iemolo, Attilio
Sabino, Valentina
Petrosino, Stefania
Steardo, Luca
Rice, Kenner C.
Orlando, Pierangelo
Iannotti, Fabio Arturo
Di Marzo, Vincenzo
Zorrilla, Eric P.
Cottone, Pietro
TI Rimonabant Precipitates Anxiety in Rats Withdrawn from Palatable Food:
Role of the Central Amygdala
SO NEUROPSYCHOPHARMACOLOGY
LA English
DT Article
DE obesity; eating disorders; compulsive eating; withdrawal; SR141716A;
endocannabinoids
ID CORTICOTROPIN-RELEASING-FACTOR; ELEVATED PLUS-MAZE; DARK SIDE;
ENDOCANNABINOID SYSTEM; CANNABINOID WITHDRAWAL; RECEPTOR ANTAGONISTS;
INTERMITTENT ACCESS; ABSTINENCE SYNDROME; COCAINE SEEKING; PREFERRED
FOOD
AB The anti-obesity medication rimonabant, an antagonist of cannabinoid type-1 (CB1) receptor, was withdrawn from the market because of adverse psychiatric side effects, including a negative affective state. We investigated whether rimonabant precipitates a negative emotional state in rats withdrawn from palatable food cycling. The effects of systemic administration of rimonabant on anxiety-like behavior, food intake, body weight, and adrenocortical activation were assessed in female rats during withdrawal from chronic palatable diet cycling. The levels of the endocannabinoids, anandamide and 2-arachidonoylglycerol (2-AG), and the CB1 receptor mRNA and the protein in the central nucleus of the amygdala (CeA) were also investigated. Finally, the effects of microinfusion of rimonabant in the CeA on anxiety-like behavior, and food intake were assessed. Systemic administration of rimonabant precipitated anxiety-like behavior and anorexia of the regular chow diet in rats withdrawn from palatable diet cycling, independently from the degree of adrenocortical activation. These behavioral observations were accompanied by increased 2-AG, CB1 receptor mRNA, and protein levels selectively in the CeA. Finally, rimonabant, microinfused directly into the CeA, precipitated anxiety-like behavior and anorexia. Our data show that (i) the 2-AG-CB1 receptor system within the CeA is recruited during abstinence from palatable diet cycling as a compensatory mechanism to dampen anxiety, and (ii) rimonabant precipitates a negative emotional state by blocking the beneficial heightened 2-AG-CB1 receptor signaling in this brain area. These findings help elucidate the link between compulsive eating and anxiety, and it will be valuable to develop better pharmacological treatments for eating disorders and obesity.
C1 [Blasio, Angelo; Iemolo, Attilio; Sabino, Valentina; Cottone, Pietro] Boston Univ, Sch Med, Lab Addict Disorders, Dept Pharmacol & Psychiat, Boston, MA 02118 USA.
[Petrosino, Stefania; Iannotti, Fabio Arturo; Di Marzo, Vincenzo] CNR, Inst Biomol Chem, Endocannabinoid Res Grp, Pozzuoli, Italy.
[Steardo, Luca] Univ Roma La Sapienza, Dept Physiol & Pharmacol, I-00185 Rome, Italy.
[Rice, Kenner C.] NIDA, Chem Biol Res Branch, Rockville, MD USA.
[Rice, Kenner C.] NIAAA, Rockville, MD 20852 USA.
[Orlando, Pierangelo] CNR, Endocannabinoid Res Grp, Inst Prot Biochem, Naples, Italy.
[Zorrilla, Eric P.] Scripps Res Inst, Comm Neurobiol Addict Disorders, La Jolla, CA 92037 USA.
RP Cottone, P (reprint author), Boston Univ, Sch Med, Lab Addict Disorders, Dept Pharmacol & Psychiat, 72 E Concord St,R-618, Boston, MA 02118 USA.
EM ezorrill@scripps.edu; cottone@bu.edu
RI Cottone, Pietro/F-5291-2012; Sabino, Valentina/F-5290-2012;
OI Cottone, Pietro/0000-0003-1320-1672; Sabino,
Valentina/0000-0002-6680-1279; Steardo, Luca/0000-0003-3570-2195; Di
Marzo, Vincenzo/0000-0002-1490-3070
FU National Institute on Drug Abuse (NIDA) [DA023680, DA030425, MH091945,
MH093650, AA016731, AA06420, DK070118]; National Institute of Mental
Health (NIMH); National Institute on Alcohol Abuse and Alcoholism
(NIAAA); National Institute on Diabetes, Digestive and Kidney Disorders;
Peter Paul Career Development Professorship; Boston University's
Undergraduate Research Opportunities Program (UROP); NIH Intramural
Research Programs of the National Institute on Drug Abuse; National
Institute of Alcohol Abuse and Alcoholism, NIH, DHHS
FX This publication was made possible by grant numbers DA023680, DA030425,
MH091945, MH093650, AA016731, AA06420, and DK070118 from the National
Institute on Drug Abuse (NIDA), the National Institute of Mental Health
(NIMH), the National Institute on Alcohol Abuse and Alcoholism (NIAAA),
and the National Institute on Diabetes, Digestive and Kidney Disorders,
by the Peter Paul Career Development Professorship (P.C.) and by Boston
University's Undergraduate Research Opportunities Program (UROP). This
research was also supported by the NIH Intramural Research Programs of
the National Institute on Drug Abuse, and the National Institute of
Alcohol Abuse and Alcoholism, NIH, DHHS. The authors declare no conflict
of interest.
NR 57
TC 11
Z9 11
U1 2
U2 10
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 0893-133X
EI 1740-634X
J9 NEUROPSYCHOPHARMACOL
JI Neuropsychopharmacology
PD NOV
PY 2013
VL 38
IS 12
BP 2498
EP 2507
DI 10.1038/npp.2013.153
PG 10
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 235IF
UT WOS:000325710200018
PM 23793355
ER
PT J
AU Wiener, L
Vasserman-Stokes, E
Battles, H
Loucas, C
Muriel, A
AF Wiener, Lori
Vasserman-Stokes, Elaina
Battles, Haven
Loucas, Caitlyn
Muriel, Anna
TI How Helpful is Dyadic Coping to Parents' Relationship During the
Pediatric Cancer Experience?
SO PSYCHO-ONCOLOGY
LA English
DT Meeting Abstract
C1 [Wiener, Lori; Vasserman-Stokes, Elaina; Battles, Haven] NCI, Bethesda, MD 20892 USA.
[Loucas, Caitlyn; Muriel, Anna] Dana Farber Canc Inst, Boston, MA 02115 USA.
NR 0
TC 0
Z9 0
U1 0
U2 4
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1057-9249
EI 1099-1611
J9 PSYCHO-ONCOLOGY
JI Psycho-Oncol.
PD NOV
PY 2013
VL 22
SU 3
SI SI
BP 3
EP 3
PG 1
WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences,
Biomedical
SC Oncology; Psychology; Biomedical Social Sciences
GA 235AS
UT WOS:000325687200005
ER
PT J
AU Galway, K
Black, A
Cantwell, M
Cardwell, C
Mills, M
Donnelly, M
AF Galway, Karen
Black, Amanda
Cantwell, Marie
Cardwell, Chris
Mills, Moyra
Donnelly, Michael
TI Psychosocial Interventions to Improve Quality of Life and Emotional
Wellbeing for Recently Diagnosed Cancer Patients
SO PSYCHO-ONCOLOGY
LA English
DT Meeting Abstract
C1 [Galway, Karen; Cantwell, Marie; Cardwell, Chris; Donnelly, Michael] Queens Univ Belfast, Belfast BT7 1NN, Antrim, North Ireland.
[Black, Amanda] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 1
U2 12
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1057-9249
EI 1099-1611
J9 PSYCHO-ONCOLOGY
JI Psycho-Oncol.
PD NOV
PY 2013
VL 22
SU 3
SI SI
BP 253
EP 254
PG 2
WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences,
Biomedical
SC Oncology; Psychology; Biomedical Social Sciences
GA 235AS
UT WOS:000325687200394
ER
PT J
AU Joyce, DW
Averbeck, BB
Frith, CD
Shergill, SS
AF Joyce, D. W.
Averbeck, B. B.
Frith, C. D.
Shergill, S. S.
TI Examining belief and confidence in schizophrenia
SO PSYCHOLOGICAL MEDICINE
LA English
DT Article
DE Belief; computational model; delusions; metacognition; schizophrenia
ID DECISION-MAKING; PREFRONTAL CORTEX; PERSECUTORY DELUSIONS; ACTION
SELECTION; LINKING BIOLOGY; DOPAMINE; METACOGNITION; CONCLUSIONS;
PERFORMANCE; PREDICTION
AB Background. People with psychoses often report fixed, delusional beliefs that are sustained even in the presence of unequivocal contrary evidence. Such delusional beliefs are the result of integrating new and old evidence inappropriately in forming a cognitive model. We propose and test a cognitive model of belief formation using experimental data from an interactive 'Rock Paper Scissors' (RPS) game.
Method. Participants (33 controls and 27 people with schizophrenia) played a competitive, time-pressured interactive two-player game (RPS). Participants' behavior was modeled by a generative computational model using leaky integrator and temporal difference methods. This model describes how new and old evidence is integrated to form a playing strategy to beat the opponent and to provide a mechanism for reporting confidence in one's playing strategy to win against the opponent.
Results. People with schizophrenia fail to appropriately model their opponent's play despite consistent (rather than random) patterns that can be exploited in the simulated opponent's play. This is manifest as a failure to weigh existing evidence appropriately against new evidence. Furthermore, participants with schizophrenia show a 'jumping to conclusions' (JTC) bias, reporting successful discovery of a winning strategy with insufficient evidence.
Conclusions. The model presented suggests two tentative mechanisms in delusional belief formation: (i) one for modeling patterns in other's behavior, where people with schizophrenia fail to use old evidence appropriately, and (ii) a metacognitive mechanism for 'confidence' in such beliefs, where people with schizophrenia overweight recent reward history in deciding on the value of beliefs about the opponent.
C1 [Joyce, D. W.; Shergill, S. S.] Kings Coll London, Inst Psychiat, Cognit Schizophrenia & Imaging Lab, Dept Psychosis Studies, London SE5 8AF, England.
[Averbeck, B. B.] NIMH, Neuropsychol Lab, NIH, Bethesda, MD 20892 USA.
[Frith, C. D.] UCL, Wellcome Ctr Imaging Neurosci, London WC1E 6BT, England.
RP Shergill, SS (reprint author), Kings Coll London, Inst Psychiat, Cognit Schizophrenia & Imaging Lab, POB 96,Crespigny Pk, London SE5 8AF, England.
EM Sukhi.Shergill@kcl.ac.uk
RI Nagra, Sasha/I-8863-2014
FU Medical Research Centre (MRC)
FX S.S.S. was funded by a Medical Research Centre (MRC) New Investigator
Award.
NR 68
TC 8
Z9 8
U1 2
U2 17
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 2013
VL 43
IS 11
BP 2327
EP 2338
DI 10.1017/S0033291713000263
PG 12
WC Psychology, Clinical; Psychiatry; Psychology
SC Psychology; Psychiatry
GA 234KB
UT WOS:000325641200009
PM 23521846
ER
PT J
AU Szot, CS
Buchanan, CF
Freeman, JW
Rylander, MN
AF Szot, Christopher S.
Buchanan, Cara F.
Freeman, Joseph W.
Rylander, Marissa Nichole
TI In Vitro Angiogenesis Induced by Tumor-Endothelial Cell Co-Culture in
Bilayered, Collagen I Hydrogel Bioengineered Tumors
SO TISSUE ENGINEERING PART C-METHODS
LA English
DT Article
ID FIBROBLAST-GROWTH-FACTOR; CANCER CELLS; INDUCTION; EXPRESSION; INVASION;
HYPOXIA; INVITRO; SWITCH; MODEL
AB Although successful remission has been achieved when cancer is diagnosed and treated during its earliest stages of development, a tumor that has established neovascularization poses a significantly greater risk of mortality. The inability to recapitulate the complexities of a maturing in vivo tumor microenvironment in an in vitro setting has frustrated attempts to identify and test anti-angiogenesis therapies that are effective at permanently halting cancer progression. We have established an in vitro tumor angiogenesis model driven solely by paracrine signaling between MDA-MB-231 breast cancer cells and telomerase-immortalized human microvascular endothelial (TIME) cells co-cultured in a spatially relevant manner. The bilayered bioengineered tumor model consists of TIME cells cultured as an endothelium on the surface of an acellular collagen I hydrogel under which MDA-MB-231 cells are cultured in a separate collagen I hydrogel. Results showed that TIME cells co-cultured with the MDA-MB-231 cells demonstrated a significant increase in cell number, rapidly developed an elongated morphology, and invasively sprouted into the underlying acellular collagen I layer. Comparatively, bioengineered tumors cultured with less aggressive MCF7 breast cancer cells did not elicit an angiogenic response. Angiogenic sprouting was demonstrated by the formation of a complex capillary-like tubule network beneath the surface of a confluent endothelial monolayer with lumen formation and anastomosing branches. In vitro angiogenesis was dependent on vascular endothelial growth factor secretion, matrix concentration, and duration of co-culture. Basic fibroblast growth factor supplemented to the co-cultures augmented angiogenic sprouting. The development of improved preclinical tumor angiogenesis models, such as the one presented here, is critical for accurate evaluation and refinement of anti-angiogenesis therapies.
C1 [Szot, Christopher S.; Buchanan, Cara F.; Rylander, Marissa Nichole] Wake Forest Univ, Virginia Polytech Inst, Sch Biomed Engn & Sci, Blacksburg, VA USA.
[Freeman, Joseph W.] Rutgers State Univ, Dept Biomed Engn, Piscataway, NJ USA.
[Rylander, Marissa Nichole] Virginia Polytech Inst & State Univ, Dept Mech Engn, Blacksburg, VA 24061 USA.
RP Szot, CS (reprint author), NCI, Mouse Canc Genet Program, Tumor Angiogenesis Sect, Frederick Natl Lab Canc Res, POB B,Bldg 560 1050 Boyles St, Frederick, MD 21702 USA.
EM szotc@vt.edu
RI Rylander, Marissa Nichole/F-2455-2014
FU National Science Foundation [CBET 0955072]; National Institute of Health
[1R21CA158454-01A1]
FX The authors would like to thank Andrea Martin for generously donating
the Sprague Dawley rat tails for collagen isolation. Funding for this
study was provided by the National Science Foundation Early CAREER Award
CBET 0955072 and the National Institute of Health grant
1R21CA158454-01A1.
NR 37
TC 20
Z9 20
U1 0
U2 35
PU MARY ANN LIEBERT, INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1937-3384
EI 1937-3392
J9 TISSUE ENG PART C-ME
JI Tissue Eng. Part C-Methods
PD NOV 1
PY 2013
VL 19
IS 11
BP 864
EP 874
DI 10.1089/ten.tec.2012.0684
PG 11
WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell
Biology
SC Cell Biology; Biotechnology & Applied Microbiology
GA 234JJ
UT WOS:000325639100005
PM 23516987
ER
PT J
AU Zazerskaya, IE
Ishkaraeva, VV
Frolova, EV
Solodovnikova, NG
Grigorova, YN
Adair, CD
Fedorova, OV
Bagrov, AY
AF Zazerskaya, Irina E.
Ishkaraeva, Valentina V.
Frolova, Elena V.
Solodovnikova, Nelly G.
Grigorova, Yulia N.
Adair, C. David
Fedorova, Olga V.
Bagrov, Alexei Y.
TI Magnesium Sulfate Potentiates Effect of Digifab on
Marinobufagenin-Induced Na/K-ATPase Inhibition
SO AMERICAN JOURNAL OF HYPERTENSION
LA English
DT Article
DE blood pressure; cardiotonic steroids; digifab; digitalis-like factors;
hypertension; immunotherapy; magnesium; marinobufagenin; NA; K-ATPase;
preeclampsia
ID PREECLAMPSIA; ECLAMPSIA; SODIUM
AB Immunoneutralization of elevated circulating levels of endogenous digitalis-like Na/K-ATPase inhibitors (i.e. cardiotonic steroids (CTS)) represents a novel approach in the treatment of preeclampsia (PE). Recently we demonstrated that DigiFab (Fab fragments of affinity-purified ovine digoxin antibody) restores PE-induced inhibition of Na/K-ATPase in erythrocytes ex vivo. Previously magnesium ions were shown to antagonize digitalis-induced toxicity, which is mediated by Na/K-ATPase inhibition. We hypothesized that magnesium sulfate would potentiate the effect of DigiFab in the reversal of CTS-induced Na/K-ATPase inhibition.
To test this hypothesis, we studied the ex vivo effect of DigiFab on Na/K-ATPase activity in erythrocytes from patients with PE in the absence and in the presence of 3 mmol/L magnesium sulfate.
Compared with 11 normotensive pregnant subjects (291 years; gestational age 39.00.2 weeks; blood pressure 1112/732mm Hg), the 12 patients with PE (301 years; gestational age 37.90.3 weeks; blood pressure 1595/993mm Hg) had plasma levels of marino bufagenin increased 3-fold (1.380.40 vs. 0.380.10 nmol/L; P < 0.01) and activity of Na/K-ATPase in erythrocytes was inhibited (1.160.11 vs. 2.800.20 mol Pi/ml/h; P < 0.01). Ex vivo, DigiFab (1 g/ml) restored erythrocyte Na/K-ATPase activity (1.720.13 mol Pi/ml/h; P < 0.01), and 3 mmol magnesium sulfate potentiated the effect of DigiFab (2.300.20 mol Pi/ml/h; P < 0.01).
Magnesium is capable of increasing the efficacy of immunoneutralization of marinobufagenin-induced Na/K-ATPase inhibition.
C1 [Zazerskaya, Irina E.; Ishkaraeva, Valentina V.; Solodovnikova, Nelly G.; Grigorova, Yulia N.] Almazov Fed Heart Blood & Endocrinol Ctr, Inst Neonatol, St Petersburg, Russia.
[Zazerskaya, Irina E.; Ishkaraeva, Valentina V.; Solodovnikova, Nelly G.; Grigorova, Yulia N.] Almazov Fed Heart Blood & Endocrinol Ctr, Inst Heart & Vessels, St Petersburg, Russia.
[Frolova, Elena V.] Sechenov Inst Evolutionary Physiol & Biochem, St Petersburg, Russia.
[Grigorova, Yulia N.; Fedorova, Olga V.; Bagrov, Alexei Y.] NIA, NIH, Baltimore, MD 21224 USA.
[Adair, C. David] Univ Tennessee, Dept Obstet & Gynecol, Chattanooga, TN USA.
RP Bagrov, AY (reprint author), NIA, NIH, Baltimore, MD 21224 USA.
EM bagrova@mail.nih.gov
FU National Institute on Aging, National Institutes of Health; Ministry of
Science and Education of Russian Federation [14.740.11.0928]; Glenveigh
Pharmaceuticals, Chattanooga, Tennessee
FX This work was supported by Intramural Research Program, National
Institute on Aging, National Institutes of Health (O.V.F. and A.Y.B.);
by a grant from Ministry of Science and Education of Russian Federation
Nr. 14.740.11.0928 (I.E.Z., V. V. I., E. V. F., N.G.S.); and by
Glenveigh Pharmaceuticals, Chattanooga, Tennessee (C. D. A.). We are
grateful to Brigit Sullivan, NIH Library, for editing assistance.
NR 14
TC 0
Z9 0
U1 1
U2 6
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0895-7061
EI 1941-7225
J9 AM J HYPERTENS
JI Am. J. Hypertens.
PD NOV
PY 2013
VL 26
IS 11
BP 1269
EP 1272
DI 10.1093/ajh/hpt117
PG 4
WC Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 232HW
UT WOS:000325484800003
PM 23878005
ER
PT J
AU Chen, JQ
Heldman, MR
Herrmann, MA
Kedei, N
Woo, W
Blumberg, PM
Goldsmith, PK
AF Chen, Jin-Qiu
Heldman, Madeleine R.
Herrmann, Michelle A.
Kedei, Noemi
Woo, Wonhee
Blumberg, Peter M.
Goldsmith, Paul K.
TI Absolute quantitation of endogenous proteins with precision and accuracy
using a capillary Western system
SO ANALYTICAL BIOCHEMISTRY
LA English
DT Article
DE Protein kinase C (PKC); Capillary immunoassay; Simple Western;
Quantitative protein analysis
ID BIOMARKER DISCOVERY; MESSENGER-RNA; PHORBOL ESTER; BRYOSTATIN 1;
KINASE-C; CELL; EXPRESSION; CANCER; PROSTATE; ANALOGS
AB Precise and accurate quantification of protein expression levels in a complex biological setting is challenging. Here, we describe a method for absolute quantitation of endogenous proteins in cell lysates using an automated capillary immunoassay system, the size-based Simple Western system (recently developed by ProteinSimple). The method was able to accurately measure the absolute amounts of target proteins at picogram or sub-picogram levels per nanogram of cell lysates. The measurements were independent of the cell matrix or the cell lysis buffer and were not affected by different antibody affinities for their specific epitopes. We then applied this method to quantitate absolute levels of expression of protein kinase C (PKC) isoforms in LNCaP and U937 cells, two cell lines used extensively for probing the downstream biological responses to PKC targeted ligands. Our absolute quantitation confirmed the predominance of PKC delta in both cells, supporting the important functional role of this PKC isoform in these cell lines. The method described here provides an approach to accurately quantitate levels of protein expression and correlate protein level with function. In addition to enhanced accuracy relative to conventional Western analysis, it circumvents the distortions inherent in comparison with signal intensities from different antibodies with different affinities. Published by Elsevier Inc.
C1 [Chen, Jin-Qiu; Heldman, Madeleine R.; Herrmann, Michelle A.] NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA.
[Kedei, Noemi; Woo, Wonhee; Blumberg, Peter M.] NCI, Lab Canc Biol & Genet, NIH, Bethesda, MD 20892 USA.
[Goldsmith, Paul K.] NCI, Off Sci & Technol Partnership, Off Director, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
RP Chen, JQ (reprint author), NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA.
EM chenj13@mail.nih.gov
FU Intramural Research Program, Center for Cancer Research, National Cancer
Institute, National Institutes of Health [Z1A BC 005270, Z1C BC 011434]
FX This research was supported by the Intramural Research Program, Center
for Cancer Research, National Cancer Institute, National Institutes of
Health (Z1A BC 005270, Z1C BC 011434).
NR 19
TC 24
Z9 25
U1 2
U2 18
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0003-2697
J9 ANAL BIOCHEM
JI Anal. Biochem.
PD NOV 1
PY 2013
VL 442
IS 1
BP 97
EP 103
DI 10.1016/j.ab.2013.07.022
PG 7
WC Biochemical Research Methods; Biochemistry & Molecular Biology;
Chemistry, Analytical
SC Biochemistry & Molecular Biology; Chemistry
GA 225OL
UT WOS:000324972100012
PM 23896461
ER
PT J
AU Shah, R
Stieltjes, B
Andrulis, M
Pfeiffer, R
Sumkauskaite, M
Delorme, S
Schlemmer, HP
Goldschmidt, H
Landgren, O
Hillengass, J
AF Shah, Rajiv
Stieltjes, Bram
Andrulis, Mindaugas
Pfeiffer, Ruth
Sumkauskaite, Migle
Delorme, Stefan
Schlemmer, Heinz-Peter
Goldschmidt, Hartmut
Landgren, Ola
Hillengass, Jens
TI Intravoxel incoherent motion imaging for assessment of bone marrow
infiltration of monoclonal plasma cell diseases
SO ANNALS OF HEMATOLOGY
LA English
DT Article
DE Diffusion-weighted imaging; Monoclonal gammopathy of undetermined
significance; Multiple myeloma; Cellularity; Microcirculation
ID APPARENT DIFFUSION-COEFFICIENT; POSITRON-EMISSION-TOMOGRAPHY; DIAGNOSED
MULTIPLE-MYELOMA; SURVIVAL; TRANSPLANTATION; GAMMOPATHIES; PATTERN; MRI
AB Modern imaging techniques have demonstrated that monoclonal plasma cell diseases infiltrate the bone marrow in a diffuse, focal, mixed pattern. While focal lesions can be easily counted and measured, the diffuse lesions of the infiltration are hard to assess. We therefore investigated 31 patients with monoclonal plasma cell diseases of all stages with intravoxel incoherent motion imaging of the same region of the pelvis from where afterwards a biopsy was obtained. We found a significant correlation between plasma cell percentage in bone marrow histology and the imaging parameters "apparent diffusion coefficient" and the diffusion coefficient D. Furthermore, those parameters correlated with other factors of disease activity, e.g., monoclonal protein, hemoglobin, and immunoparesis. In summary, we found that the non-invasively acquired imaging parameters correlated with the degree of plasma cell infiltration in the bone marrow.
C1 [Shah, Rajiv; Stieltjes, Bram; Sumkauskaite, Migle; Delorme, Stefan; Schlemmer, Heinz-Peter] German Canc Res Ctr, Heidelberg, Germany.
[Andrulis, Mindaugas] Heidelberg Univ, Inst Pathol, Heidelberg, Germany.
[Pfeiffer, Ruth; Landgren, Ola] NCI, NIH, Bethesda, MD 20892 USA.
[Goldschmidt, Hartmut; Hillengass, Jens] Univ Heidelberg Hosp, Dept Hematol Oncol & Rheumatol, D-69126 Heidelberg, Germany.
[Shah, Rajiv] Univ Heidelberg Hosp, Dept Thorac Oncol, Thoraxklin, D-69126 Heidelberg, Germany.
RP Shah, R (reprint author), Univ Heidelberg Hosp, Dept Thorac Oncol, Thoraxklin, Amalienstr 5, D-69126 Heidelberg, Germany.
EM rajiv.shah@thoraxklinik-heidelberg.de
OI Delorme, Stefan/0000-0002-1000-2582
FU German Research Foundation (Transregio 79); International Myeloma
Foundation
FX Parts of this study have been supported by a grant from the German
Research Foundation (Transregio 79) and a grant from the International
Myeloma Foundation.
NR 20
TC 3
Z9 3
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0939-5555
J9 ANN HEMATOL
JI Ann. Hematol.
PD NOV
PY 2013
VL 92
IS 11
BP 1553
EP 1557
DI 10.1007/s00277-013-1786-1
PG 5
WC Hematology
SC Hematology
GA 230QQ
UT WOS:000325357600014
PM 23680869
ER
PT J
AU Meissner, A
Boshoff, HI
Vasan, M
Duckworth, BP
Barry, CE
Aldrich, CC
AF Meissner, Anja
Boshoff, Helena I.
Vasan, Mahalakshmi
Duckworth, Benjamin P.
Barry, Clifton E., III
Aldrich, Courtney C.
TI Structure-activity relationships of 2-aminothiazoles effective against
Mycobacterium tuberculosis
SO BIOORGANIC & MEDICINAL CHEMISTRY
LA English
DT Article
DE Mycobacterium tuberculosis; Aminothiazole; High-throughput screening;
Antibacterial agent
ID PHARMACOKINETIC PROPERTIES; AGENTS; STREPTOMYCIN; HETEROCYCLES;
ANTIBIOTICS; DERIVATIVES; INHIBITORS; GROWTH
AB A series of 2-aminothiazoles was synthesized based on a HTS scaffold from a whole-cell screen against Mycobacterium tuberculosis (Mtb). The SAR shows the central thiazole moiety and the 2-pyridyl moiety at C-4 of the thiazole are intolerant to modification. However, the N-2 position of the aminothiazole exhibits high flexibility and we successfully improved the antitubercular activity of the initial hit by more than 128-fold through introduction of substituted benzoyl groups at this position. N-(3-Chlorobenzoyl)-4-(2-pyridinyl)-1,3-thiazol-2-amine (55) emerged as one of the most promising analogues with a MIC of 0.024 mu M or 0.008 mu g/mL in 7H9 media and therapeutic index of nearly similar to 300. However, 55 is rapidly metabolized by human liver microsomes (t(1/2) = 28 min) with metabolism occurring at the invariant aminothiazole moiety and Mtb develops spontaneous low-level resistance with a frequency of similar to 10 (5). (C) 2013 Elsevier Ltd. All rights reserved.
C1 [Meissner, Anja; Vasan, Mahalakshmi; Duckworth, Benjamin P.; Aldrich, Courtney C.] Univ Minnesota, Acad Hlth Ctr, Ctr Drug Design, Minneapolis, MN 55455 USA.
[Boshoff, Helena I.; Barry, Clifton E., III] NIAID, TB Res Sect, Bethesda, MD 20892 USA.
RP Aldrich, CC (reprint author), Univ Minnesota, Acad Hlth Ctr, Ctr Drug Design, Minneapolis, MN 55455 USA.
EM aldri015@umn.edu
RI Barry, III, Clifton/H-3839-2012
FU National Institutes of Health [AI070219]; NIAID, NIH
FX This research was supported by a National Institutes of Health Grant
AI070219 (to C.C.A.) and the Intramural Research Program of the NIAID,
NIH.
NR 47
TC 16
Z9 16
U1 0
U2 19
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 2013
VL 21
IS 21
BP 6385
EP 6397
DI 10.1016/j.bmc.2013.08.048
PG 13
WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry,
Organic
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry
GA 228DC
UT WOS:000325164500013
PM 24075144
ER
PT J
AU Ha, TH
Ryu, H
Kim, SE
Kim, HS
Ann, J
Tran, PT
Hoang, VH
Son, K
Cui, MH
Choi, S
Blumberg, PM
Frank, R
Bahrenberg, G
Schiene, K
Christoph, T
Frormann, S
Lee, J
AF Ha, Tae-Hwan
Ryu, HyungChul
Kim, Sung-Eun
Kim, Ho Shin
Ann, Jihyae
Tran, Phuong-Thao
Hoang, Van-Hai
Son, Karam
Cui, Minghua
Choi, Sun
Blumberg, Peter M.
Frank, Robert
Bahrenberg, Gregor
Schiene, Klaus
Christoph, Thomas
Frormann, Sven
Lee, Jeewoo
TI TRPV1 antagonist with high analgesic efficacy: 2-Thio pyridine C-region
analogues of 2-(3-fluoro-4-methylsulfonylaminophenyl)propanamides
SO BIOORGANIC & MEDICINAL CHEMISTRY
LA English
DT Article
DE TRPV1 antagonists; Analgesic; Capsaicin; Resiniferatoxin
ID CAPSAICIN RECEPTORS; RESINIFERATOXIN; TARGET
AB A series of 2-thio pyridine C-region analogues of 2-(3-fluoro-4-methylsulfonylaminophenyl)propanamides were investigated as hTRPV1 antagonists. Among them, compound 24S showed stereospecific and excellent TRPV1 antagonism of capsaicin-induced activation. Further, it demonstrated strong anti-allodynic in a rat neuropathic pain model. Consistent with its action in vitro being through TRPV1, compound 24S blocked capsaicin-induced hypothermia in mice. Docking analysis of 24S with our hTRPV1 homology model was performed to identify its binding mode. (C) 2013 Elsevier Ltd. All rights reserved.
C1 [Ha, Tae-Hwan; Ryu, HyungChul; Kim, Sung-Eun; Kim, Ho Shin; Ann, Jihyae; Tran, Phuong-Thao; Hoang, Van-Hai; Lee, Jeewoo] Seoul Natl Univ, Pharmaceut Sci Res Inst, Coll Pharm, Med Chem Lab, Seoul 151742, South Korea.
[Son, Karam; Cui, Minghua; Choi, Sun] Ewha Womans Univ, Div Life & Pharmaceut Sci, Natl Leading Res Lab NLRL Mol Modeling & Drug Des, Coll Pharm, Seoul 120750, South Korea.
[Son, Karam; Cui, Minghua; Choi, Sun] Ewha Womans Univ, Global Res Program Top5, Seoul 120750, South Korea.
[Blumberg, Peter M.] NCI, Lab Canc Biol & Genet, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Frank, Robert; Bahrenberg, Gregor; Schiene, Klaus; Christoph, Thomas; Frormann, Sven] 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; National Research Foundation of Korea (NRF)
[R11-2007-107-02001-0]; National Leading Research Lab (NLRL) program
[2011-0028885]; Intramural Research Program of NIH, Center for Cancer
Research, NCI [Z1A BC 005270]
FX This research was supported by Research Grants from Grunenthal, Grants
from the National Research Foundation of Korea (NRF)
(R11-2007-107-02001-0), Grants from the National Leading Research Lab
(NLRL) program (2011-0028885), and in part by the Intramural Research
Program of NIH, Center for Cancer Research, NCI (Project Z1A BC 005270).
NR 23
TC 9
Z9 9
U1 2
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 2013
VL 21
IS 21
BP 6657
EP 6664
DI 10.1016/j.bmc.2013.08.015
PG 8
WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry,
Organic
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry
GA 228DC
UT WOS:000325164500042
PM 24035514
ER
PT J
AU MacDonough, MT
Strecker, TE
Hamel, E
Hall, JJ
Chaplin, DJ
Trawick, ML
Pinney, KG
AF MacDonough, Matthew T.
Strecker, Tracy E.
Hamel, Ernest
Hall, John J.
Chaplin, David J.
Trawick, Mary Lynn
Pinney, Kevin G.
TI Synthesis and biological evaluation of indole-based, anti-cancer agents
inspired by the vascular disrupting agent 2-(3 '-hydroxy-4
'-methoxyphenyl)-3-(3 '',4 '',5 ''-trimethoxybenzoyl)-6-methoxyindole
(OXi8006)
SO BIOORGANIC & MEDICINAL CHEMISTRY
LA English
DT Article
DE Vascular disrupting agent (VDA); Inhibitor of tubulin assembly;
Functionalized indole; Combretastatin
ID ANTINEOPLASTIC AGENTS; TUBULIN POLYMERIZATION; COMBRETASTATIN A-4;
COMBRETUM-CAFFRUM; BINDING-ACTIVITY; INHIBITORS; POTENT; ANALOGS;
CYTOTOXICITY; MICROTUBULES
AB The discovery of a 2-aryl-3-aroyl indole-based small-molecule inhibitor of tubulin assembly (referred to as OXi8006) inspired the design, synthesis, and biological evaluation of a series of diversely functionalized analogues. In the majority of examples, the pendant 2-aryl ring contained a 3-hydroxy-4-methoxy substitution pattern, and the fused aryl ring featured a 6-methoxy group. Most of the variability was in the 3-aroyl moiety, which was modified to incorporate methoxy (33-36), nitro (25-27), halogen (28-29), trifluoromethyl (30), or trifluoromethoxy (31-32) functionalities. In two analogues (34 and 36), the methoxy substitution pattern in the fused aryl ring varied, while in another derivative (35) the phenolic moiety was translocated from the pendant 2-aryl ring to position-7 of the fused aryl ring. Each of the compounds were evaluated for their cytotoxicity (in vitro) against the SK-OV-3 (ovarian), NCI-H460 (lung), and DU-145 (prostate) human cancer cell lines and for their ability to inhibit tubulin assembly. Four of the compounds (30, 31, 35, 36) proved to be potent inhibitors of tubulin assembly (IC50 < 5 mu M), and three of these compounds (31, 35, 36) were strongly cytotoxic against the three cancer cell lines. The most active compound (36) in this series, which incorporated a methoxy group at position-7, was comparable in terms of inhibition of tubulin assembly and cytotoxicity to the lead compound OXi8006. (C) 2013 Elsevier Ltd. All rights reserved.
C1 [MacDonough, Matthew T.; Strecker, Tracy E.; Hall, John J.; Trawick, Mary Lynn; Pinney, Kevin G.] Baylor Univ, Dept Chem & Biochem, Waco, TX 76798 USA.
[Hamel, Ernest] NCI, Screening Technol Branch, Dev Therapeut Program,NIH, Div Canc Treatment & Diag,Frederick Natl Lab Canc, Frederick, MD 21702 USA.
[Chaplin, David J.] Oxigene Inc, San Francisco, CA 94080 USA.
RP Pinney, KG (reprint author), Baylor Univ, Dept Chem & Biochem, 1 Bear Pl 97348, Waco, TX 76798 USA.
EM Kevin_Pinney@baylor.edu
OI Pinney, Kevin/0000-0003-1262-8631
FU National Cancer Institute of the National Institutes of Health
[5R01CA140674]; Oxigene Inc.; NSF [CHE-0420802]
FX The authors are grateful to the National Cancer Institute of the
National Institutes of Health (Grant No. 5R01CA140674 to K.G.P. and
M.L.T.) and Oxigene Inc. (grant to K.G.P. and M.L.T.) for their
financial support of this project, and to the NSF for funding the Varian
500 MHz NMR spectrometer (Grant No. CHE-0420802). The content is solely
the responsibility of the authors and does not necessarily reflect the
official views of the National Institutes of Health. The authors also
thank Dr. James Karban and Dr. Michelle Nemec (Director) for the use of
the shared Molecular Biosciences Center at Baylor University, Dr.
Alejandro Ramirez (Mass Spectrometry Core Facility, Baylor University),
and Dr. Kevin Klausmeyer (X-ray analysis). The authors are grateful to
Mr. Robert Harris, Ms. Priscilla Hor, and Ms. Siri Ancha for their
valuable contributions to the synthesis of certain analogues.
NR 54
TC 20
Z9 20
U1 2
U2 20
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 2013
VL 21
IS 21
BP 6831
EP 6843
DI 10.1016/j.bmc.2013.07.028
PG 13
WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry,
Organic
SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry
GA 228DC
UT WOS:000325164500061
PM 23993969
ER
PT J
AU Alonso, WJ
Schuck-Paim, C
AF Alonso, W. J.
Schuck-Paim, C.
TI What can the 2009 influenza outbreak teach us about the risk of a severe
pandemic? The Madagascar experience
SO EPIDEMIOLOGY AND INFECTION
LA English
DT Letter
ID AFRICA
C1 [Alonso, W. J.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Alonso, W. J.; Schuck-Paim, C.] Origem Sci, Sao Paulo, Brazil.
RP Alonso, WJ (reprint author), NIH, Fogarty Int Ctr, 16 Ctr Dr,Bldg 16, Bethesda, MD 20892 USA.
EM alonsow@mail.nih.gov
NR 8
TC 2
Z9 2
U1 0
U2 5
PU CAMBRIDGE UNIV PRESS
PI NEW YORK
PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA
SN 0950-2688
J9 EPIDEMIOL INFECT
JI Epidemiol. Infect.
PD NOV
PY 2013
VL 141
IS 11
BP 2454
EP 2455
DI 10.1017/S0950268812003068
PG 2
WC Public, Environmental & Occupational Health; Infectious Diseases
SC Public, Environmental & Occupational Health; Infectious Diseases
GA 228WH
UT WOS:000325222100023
PM 23328345
ER
PT J
AU Ashmore, JH
Lesko, SM
Miller, PE
Cross, AJ
Muscat, JE
Zhu, JJ
Liao, J
Harper, G
Lazarus, P
Hartman, TJ
AF Ashmore, Joseph H.
Lesko, Samuel M.
Miller, Paige E.
Cross, Amanda J.
Muscat, Joshua E.
Zhu, Junjia
Liao, Jason
Harper, Gregory
Lazarus, Philip
Hartman, Terryl J.
TI Association of dietary and supplemental iron and colorectal cancer in a
population-based study
SO EUROPEAN JOURNAL OF CANCER PREVENTION
LA English
DT Article
DE colorectal cancer; heme; iron; supplements
ID HEME IRON; COLON-CANCER; RED MEAT; ALCOHOL-CONSUMPTION; RISK; WOMEN;
ZINC; VALIDATION; OVERLOAD; DISEASES
AB We evaluated the role of dietary iron, heme iron, and supplemental iron on colorectal cancer (CRC) risk in a population-based case-control study in Pennsylvania, including 1005 incident cases and 1062 controls. Diet was assessed through a modified food frequency questionnaire that included supplement use and a meat-specific module. Cases reported intakes for the year before diagnosis, whereas controls reported intakes for the year before interview. Heme iron intake was calculated using a new heme database developed by the US National Cancer Institute. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional logistic regression. After multivariate adjustment, there were no significant associations between heme iron or total iron intake and CRC incidence. Dietary iron intake was inversely associated with CRC among women (OR Q(5) vs. Q(1)=0.45; 95% CI=0.22-0.92), but not among men. Supplemental iron intake of more than 18 mg/day versus none was positively associated with CRC incidence (OR=2.31; 95% CI=1.48-3.59; P-trend<0.001), an effect that was observed in both men (OR=2.56; 95% CI=1.30-5.05) and women (OR=2.46; 95% CI=1.34-4.52). These findings suggest that consumption of more than 18 mg/day of supplemental iron may increase risk for CRC. (C) 2013 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.
C1 [Ashmore, Joseph H.; Hartman, Terryl J.] Penn State Univ, Dept Nutr Sci, University Pk, PA 16802 USA.
[Lesko, Samuel M.] Northeast Reg Canc Inst, Scranton, PA USA.
[Muscat, Joshua E.; Zhu, Junjia; Liao, Jason; Lazarus, Philip] Penn State Coll Med, Dept Publ Hlth Sci, Hershey, PA USA.
[Lazarus, Philip] Penn State Coll Med, Dept Pharmacol, Hershey, PA USA.
[Harper, Gregory] Lehigh Valley Hosp, Dept Med & Pharmacol, Allentown, PA USA.
[Miller, Paige E.] Exponent Inc, Dept Hlth Sci, Chicago, IL USA.
[Cross, Amanda J.] NCI, Dept Hlth & Human Serv, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
RP Ashmore, JH (reprint author), Penn State Univ, Dept Nutr Sci, 110 Chandlee Lab, University Pk, PA 16802 USA.
EM jha133@psu.edu
FU Pennsylvania Department of Health [4100038714]
FX This study was partially support by the Pennsylvania Department of
Health (Grant number 4100038714).
NR 35
TC 8
Z9 8
U1 1
U2 21
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0959-8278
J9 EUR J CANCER PREV
JI Eur. J. Cancer Prev.
PD NOV
PY 2013
VL 22
IS 6
BP 506
EP 511
DI 10.1097/CEJ.0b013e32836056f8
PG 6
WC Oncology
SC Oncology
GA 227FH
UT WOS:000325095300003
PM 23492957
ER
PT J
AU Hirabayashi, K
Shiohara, M
Yamada, K
Sueki, A
Ide, Y
Takeuchi, K
Hagimoto, R
Kinoshita, T
Yabuhara, A
Mudd, SH
Koike, K
AF Hirabayashi, Koichi
Shiohara, Masaaki
Yamada, Kazuhiro
Sueki, Akane
Ide, Yuichiro
Takeuchi, Koichi
Hagimoto, Rokuro
Kinoshita, Tatsuya
Yabuhara, Akihiko
Mudd, S. Harvey
Koike, Kenichi
TI Neurologically normal development of a patient with severe methionine
adenosyltransferase I/III deficiency after continuing dietary methionine
restriction
SO GENE
LA English
DT Article
DE Methionine adenosyltransferase I/III deficiency; Hypermethioninemia;
Homocystinuria; Dietary methionine restriction; Psychomotor development
ID BETA-SYNTHASE DEFICIENCY; S-ADENOSYLMETHIONINE; PERSISTENT
HYPERMETHIONINEMIA; HOMOCYSTINURIA; DEMYELINATION; HOMOCYSTEINE;
PATHWAY; STATES; BRAIN
AB Background: There is not much information on established standard therapy for patients with severe methionine adenosyltransferase (MAT) I/III deficiency.
Case presentation: We report a boy with MAT I/III deficiency, in whom plasma methionine and total homocysteine, and urinary homocystine were elevated. Molecular genetic studies showed him to have novel compound heterozygous mutations of the MAT1A gene: c.191T>A (p.M64K) and c.589delC (p.P197Lf5X26). A low methionine milk diet was started at 31 days of age, and during continuing dietary methionine restriction plasma methionine levels have been maintained at less than 750 mu mol/L. He is now 5 years old, and has had entirely normal physical growth and psychomotor development
Conclusions: Although some severely MAT I/III deficient patients have developed neurologic abnormalities, we report here the case of a boy who has remained neurologically and otherwise normal for 5 years during methionine restriction, suggesting that perhaps such management, started in early infancy, may help prevent neurological complications. (C) 2013 Elsevier B.V. All rights reserved.
C1 [Hirabayashi, Koichi; Hagimoto, Rokuro; Kinoshita, Tatsuya; Yabuhara, Akihiko] Ina Cent Hosp, Dept Pediat, Ina, Saitama, Japan.
[Hirabayashi, Koichi; Shiohara, Masaaki; Koike, Kenichi] Shinshu Univ, Sch Med, Dept Pediat, Matsumoto, Nagano 3908621, Japan.
[Yamada, Kazuhiro] Tokyo Univ Agr & Technol, Dept Biotechnol & Life Sci, Koganei, Tokyo, Japan.
[Sueki, Akane; Ide, Yuichiro] Shinshu Univ, Sch Med, Dept Lab Med, Matsumoto, Nagano 3908621, Japan.
[Takeuchi, Koichi] Nagano Childrens Hosp, Dept Pediat Interdisciplinary Med, Azumino, Japan.
[Mudd, S. Harvey] NIMH, Mol Biol Lab, Bethesda, MD 20892 USA.
RP Hirabayashi, K (reprint author), Shinshu Univ, Sch Med, Dept Pediat, Asahi 3-1-1, Matsumoto, Nagano 3908621, Japan.
EM kohira@shinshu-u.ac.jp
NR 31
TC 7
Z9 7
U1 0
U2 3
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0378-1119
J9 GENE
JI Gene
PD NOV 1
PY 2013
VL 530
IS 1
BP 104
EP 108
DI 10.1016/j.gene.2013.08.025
PG 5
WC Genetics & Heredity
SC Genetics & Heredity
GA 229ZV
UT WOS:000325307300015
PM 23973726
ER
PT J
AU Butterfield, RJ
Foley, AR
Dastgir, J
Asman, S
Dunn, DM
Zou, YQ
Hu, Y
Donkervoort, S
Flanigan, KM
Swoboda, KJ
Winder, TL
Weiss, RB
Bonnemann, CG
AF Butterfield, Russell J.
Foley, A. Reghan
Dastgir, Jahannaz
Asman, Stephanie
Dunn, Diane M.
Zou, Yaqun
Hu, Ying
Donkervoort, Sandra
Flanigan, Kevin M.
Swoboda, Kathryn J.
Winder, Thomas L.
Weiss, Robert B.
Boennemann, Carsten G.
TI Position of Glycine Substitutions in the Triple Helix of COL6A1, COL6A2,
and COL6A3 is Correlated with Severity and Mode of Inheritance in
Collagen VI Myopathies
SO HUMAN MUTATION
LA English
DT Article
DE collagen VI; Ullrich congenital muscular dystrophy; Bethlem myopathy;
genotype-phenotype correlation
ID CONGENITAL MUSCULAR-DYSTROPHY; BETHLEM MYOPATHY; VONWILLEBRAND-FACTOR;
SEQUENCE-ANALYSIS; GLOBULAR DOMAINS; IV COLLAGEN; MUTATIONS; DOMINANT;
COMMON; MUSCLE
AB Glycine substitutions in the conserved Gly-X-Y motif in the triple helical (TH) domain of collagen VI are the most commonly identified mutations in the collagen VI myopathies including Ullrich congenital muscular dystrophy, Bethlem myopathy, and intermediate (INT) phenotypes. We describe clinical and genetic characteristics of 97 individuals with glycine substitutions in the TH domain of COL6A1, COL6A2, or COL6A3 and add a review of 97 published cases, for a total of 194 cases. Clinical findings include severe, INT, and mild phenotypes even from patients with identical mutations. INT phenotypes were most common, accounting for almost half of patients, emphasizing the importance of INT phenotypes to the overall phenotypic spectrum. Glycine substitutions in the TH domain are heavily clustered in a short segment N-terminal to the 17th Gly-X-Y triplet, where they are acting as dominants. The most severe cases are clustered in an even smaller region including Gly-X-Y triplets 10-15, accounting for only 5% of the TH domain. Our findings suggest that clustering of glycine substitutions in the N-terminal region of collagen VI is not based on features of the primary sequence. We hypothesize that this region may represent a functional domain within the triple helix.
C1 [Butterfield, Russell J.; Asman, Stephanie; Swoboda, Kathryn J.] Univ Utah, Dept Pediat, Salt Lake City, UT USA.
[Foley, A. Reghan] Univ Utah, Dept Neurol, Salt Lake City, UT USA.
[Foley, A. Reghan] UCL Inst Child Hlth, Dubowitz Neuromuscular Ctr, London, England.
[Foley, A. Reghan] Great Ormond St Hosp Sick Children, London WC1N 3JH, England.
[Dastgir, Jahannaz; Zou, Yaqun; Hu, Ying; Donkervoort, Sandra; Boennemann, Carsten G.] NINDS, Neurogenet Branch, NIH, Bethesda, MD 20892 USA.
[Dunn, Diane M.; Weiss, Robert B.] Univ Utah, Dept Human Genet, Salt Lake City, UT USA.
[Flanigan, Kevin M.] Nationwide Childrens Hosp, Ctr Gene Therapy, Columbus, OH USA.
[Winder, Thomas L.] Prevent Genet, Marshfield, WI USA.
RP Bonnemann, CG (reprint author), Bldg 35 Porter NRC,Room 2A-116,35 Convent Dr MSC, Bethesda, MD 20892 USA.
EM carsten.bonnemann@nih.gov
OI Flanigan, Kevin/0000-0001-6440-3376
FU MDA Clinical Research Training Grant; Primary Children's Medical Center
Foundation; Eunice Kennedy Shriver National Institute of Child Health
and Human Development; National Institutes of Health [5K12HD001410-10];
Muscular Dystrophy Campaign; NIH/NINDS Intramural Research Funds
FX Contract grant sponsors: MDA Clinical Research Training Grant (RJB);
Primary Children's Medical Center Foundation (RJB); Eunice Kennedy
Shriver National Institute of Child Health and Human Development;
National Institutes of Health (5K12HD001410-10) (RJB); Muscular
Dystrophy Campaign (ARF); NIH/NINDS Intramural Research Funds (CGB).
NR 36
TC 20
Z9 20
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1059-7794
J9 HUM MUTAT
JI Hum. Mutat.
PD NOV
PY 2013
VL 34
IS 11
BP 1558
EP 1567
DI 10.1002/humu.22429
PG 10
WC Genetics & Heredity
SC Genetics & Heredity
GA 231OP
UT WOS:000325426900015
PM 24038877
ER
PT J
AU Sprung, CL
Danis, M
Iapichino, G
Artigas, A
Kesecioglu, J
Moreno, R
Lippert, A
Curtis, JR
Meale, P
Cohen, SL
Levy, MM
Truog, RD
AF Sprung, Charles L.
Danis, Marion
Iapichino, Gaetano
Artigas, Antonio
Kesecioglu, Jozef
Moreno, Rui
Lippert, Anne
Curtis, J. Randall
Meale, Paula
Cohen, Simon L.
Levy, Mitchell M.
Truog, Robert D.
TI Triage of intensive care patients: identifying agreement and controversy
SO INTENSIVE CARE MEDICINE
LA English
DT Article
DE Consensus statement; Triage; Intensive care unit; Elderly
ID CRITICALLY-ILL PATIENTS; PATIENTS REFUSED ADMISSION; DECISION-MAKING;
UNITS; MORTALITY; ICU; DETERMINANTS; ALLOCATION; RESOURCES; SURVIVAL
AB Intensive care unit (ICU) resources are limited in many hospitals. Patients with little likelihood of surviving are often admitted to ICUs. Others who might benefit from ICU are not admitted.
To provide an updated consensus statement on the principles and recommendations for the triage of patients for ICU beds.
The previous Society of Critical Care Medicine (SCCM) consensus statement was used to develop drafts of general and specific principles and recommendations. Investigators and consultants were sent the statements and responded with their agreement or disagreement.
The Eldicus project (triage decision making for the elderly in European intensive care units).
Eldicus investigators, consultants, and experts consisting of intensivists, users of ICU services, ethicists, administrators, and public policy officials.
Consensus development was used to grade the statements and recommendations.
Consensus was defined as 80 % agreement or more. Consensus was obtained for 54 (87 %) of 62 statements including all (19) general principles, 31 (86 %) of the specific principles, and 10 (71 %) of the recommendations. Inconsistencies in responses were noted for ICU admission and discharge. Despite agreement for guidelines applying to individual patients and an objective triage score, there was no agreement for a survival cutoff for triage, not even for a chance of survival of 0.1 %.
Consensus was reached for most general and specific ICU triage principles and recommendations. Further debate and discussion should help resolve the remaining discrepancies.
C1 [Sprung, Charles L.] Hadassah Hebrew Univ, Med Ctr, Dept Anesthesiol & Crit Care Med, Gen Intens Care Unit, IL-91120 Jerusalem, Israel.
[Danis, Marion] NIH, Sect Eth & Hlth Policy, Bethesda, MD 20892 USA.
[Iapichino, Gaetano] Univ Milan, San Paolo Hosp, Milan, Italy.
[Artigas, Antonio] Autonomous Univ Barcelona, Parc Tauli Univ Inst, CIBER Enfermedades Resp, Crit Care Ctr,Sabadell Hosp, Sabadell, Spain.
[Kesecioglu, Jozef] Univ Med Ctr Utrecht, Dept Intens Care Med, Utrecht, Netherlands.
[Moreno, Rui] Ctr Hosp Lisboa Cent, Hosp Sao Jose, EPE, Unidade Cuidados Intens Neurocrit, Lisbon, Portugal.
[Lippert, Anne] Herlev Univ Hosp, Copenhagen, Denmark.
[Curtis, J. Randall] Univ Washington, Harborview Med Ctr, Div Pulm & Crit Care Med, Seattle, WA 98104 USA.
[Meale, Paula] UCL, Div Surg & Intervent Sci, London, England.
[Cohen, Simon L.] UCL, Dept Intens Care Med, London, England.
[Levy, Mitchell M.] Brown Univ, Rhode Isl Hosp, Warren Alpert Med Sch, Div Pulm & Crit Care Med, Providence, RI 02903 USA.
[Truog, Robert D.] Harvard Univ, Childrens Hosp, Sch Med, Div Med Eth, Boston, MA 02115 USA.
[Truog, Robert D.] Harvard Univ, Childrens Hosp, Sch Med, Div Anaesthesiol, Boston, MA 02115 USA.
[Truog, Robert D.] Harvard Univ, Childrens Hosp, Sch Med, Div Pediat, Boston, MA 02115 USA.
RP Sprung, CL (reprint author), Hadassah Hebrew Univ, Med Ctr, Dept Anesthesiol & Crit Care Med, Gen Intens Care Unit, POB 12000, IL-91120 Jerusalem, Israel.
EM sprung@cc.huji.ac.il
FU European Commission [QLK6-CT-2002-00251]; European Society of Intensive
Care Medicine; European Critical Care Research Network; Israel National
Institute for Health Policy and Health Services Research [1998/11/G];
Red GIRA [G03/063]
FX Supported by the European Commission contract QLK6-CT-2002-00251, the
European Society of Intensive Care Medicine and the European Critical
Care Research Network, The Israel National Institute for Health Policy
and Health Services Research grant number 1998/11/G and by Red GIRA
G03/063. The EU Commission and other sponsors had no role in the design
and conduct of the study, the collection, management, analysis, and
interpretation of the data, or in the preparation, review, or approval
of the manuscript. All authors participated in the design of the study,
helped in the analysis of the data, and collaborated in drafting and
revising the manuscript. As this is a study of triage and ethical
issues, the authors' have no financial or personal relationships or
affiliations that could influence (or bias) their decisions, work, or
manuscript.
NR 33
TC 28
Z9 28
U1 0
U2 9
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0342-4642
J9 INTENS CARE MED
JI Intensive Care Med.
PD NOV
PY 2013
VL 39
IS 11
BP 1916
EP 1924
DI 10.1007/s00134-013-3033-6
PG 9
WC Critical Care Medicine
SC General & Internal Medicine
GA 227KE
UT WOS:000325110800004
PM 23925544
ER
PT J
AU Koepke, KM
Miller, B
AF Koepke, Kathleen Mann
Miller, Brett
TI At the Intersection of Math and Reading Disabilities: Introduction to
the Special Issue
SO JOURNAL OF LEARNING DISABILITIES
LA English
DT Editorial Material
DE math; reading; learning disabilities; comorbidity
ID REMEDIATING NUMBER COMBINATION; LEARNING-DIFFICULTIES; MATHEMATICS;
CHILDREN; COMORBIDITY; STUDENTS; DEFICITS; PREVALENCE; DISORDERS;
COGNITION
AB Individuals with comorbid disabilities in mathematics and reading face significant challenges in acquiring the componential skills related to each domain. Persons with these comorbid conditions are significantly understudied and this paucity of work limits how effective practitioners can be at addressing the needs of this population. In the United States, roughly 7% of all children suffer from math disability; of these, an estimated 17% to 66% also has a comorbid reading disability. Underspecification of current conceptualizations of math and reading disabilities, including how to best identify and classify individuals with one or more of these disabilities, hampers our efforts to intervene effectively. To conceptualize how to move forward in these areas, the Eunice Kennedy Shriver National Institute of Child Health and Human Development held a workshop focused on examining the etiology, classification, and remediation of comorbid math and reading disabilities. This special issue, titled At the Intersection of Math and Reading Disabilities, continues that discussion. Contributing authors articulate a path forward to address the needs of these learners and inform the foundational understanding of both conditions in isolation and as they interact.
C1 [Koepke, Kathleen Mann; Miller, Brett] US NIH, Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD 20852 USA.
RP Koepke, KM (reprint author), US NIH, Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, 6100 Execut Blvd,Suite 4B05,MSC 7510, Bethesda, MD 20852 USA.
EM kmk@nih.gov
NR 36
TC 6
Z9 6
U1 3
U2 13
PU SAGE PUBLICATIONS INC
PI THOUSAND OAKS
PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA
SN 0022-2194
J9 J LEARN DISABIL-US
JI J. Learn. Disabil.
PD NOV
PY 2013
VL 46
IS 6
SI SI
BP 483
EP 489
DI 10.1177/0022219413498200
PG 7
WC Education, Special; Rehabilitation
SC Education & Educational Research; Rehabilitation
GA 232GB
UT WOS:000325479000001
ER
PT J
AU Nicoll, RA
Roche, KW
AF Nicoll, Roger A.
Roche, Katherine W.
TI Long-term potentiation: Peeling the onion
SO NEUROPHARMACOLOGY
LA English
DT Review
DE NMDA receptor; AMPA receptor; CaMKII; Long-term potentiation; Synapse
ID AMPA RECEPTOR TRAFFICKING; SINGLE DENDRITIC SPINES; DEPENDENT KINASE-II;
SYNAPTIC PLASTICITY; HIPPOCAMPAL SLICE; PRESYNAPTIC ENHANCEMENT;
PROTEIN-SYNTHESIS; SILENT SYNAPSES; GLUR1 SUBUNIT; LTP
AB Since the discovery of long-term potentiation (LTP), thousands of papers have been published on this phenomenon. With this massive amount of information, it is often difficult, especially for someone not directly involved in the field, not to be overwhelmed. The goal of this review is to peel away as many layers as possible, and probe the core properties of LTP. We would argue that the many dozens of proteins that have been implicated in the phenomenon are not essential, but rather modulate, often in indirect ways, the threshold and/or magnitude of LTP. What is required is NMDA receptor activation followed by CaMKII activation. The consequence of CaMKII activation is the rapid recruitment of AMPA receptors to the synapse. This recruitment is independent of AMPA receptor subunit type, but absolutely requires an adequate pool of surface receptors. An important unresolved issue is how exactly CaMKII activation leads to modifications in the PSD to allow rapid enrichment.
This article is part of the Special Issue entitled 'Glutamate Receptor-Dependent Synaptic Plasticity'. (C) 2013 Elsevier Ltd. All rights reserved.
C1 [Nicoll, Roger A.] Univ Calif San Francisco, Dept Cellular & Mol Pharmacol, San Francisco, CA 94143 USA.
[Nicoll, Roger A.] Univ Calif San Francisco, Dept Physiol, San Francisco, CA 94143 USA.
[Roche, Katherine W.] NINDS, Receptor Biol Sect, NIH, Bethesda, MD 20892 USA.
RP Nicoll, RA (reprint author), Univ Calif San Francisco, Dept Cellular & Mol Pharmacol, Genentech Hall,600 16th St,Box 2140, San Francisco, CA 94143 USA.
EM roger.nicoll@ucsf.edu
OI Roche, Katherine/0000-0001-7282-6539
FU NIMH NIH HHS [R01 MH070957]; NINDS NIH HHS [P01 NS016033]
NR 65
TC 43
Z9 43
U1 4
U2 72
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0028-3908
J9 NEUROPHARMACOLOGY
JI Neuropharmacology
PD NOV
PY 2013
VL 74
SI SI
BP 18
EP 22
DI 10.1016/j.neuropharm.2013.02.010
PG 5
WC Neurosciences; Pharmacology & Pharmacy
SC Neurosciences & Neurology; Pharmacology & Pharmacy
GA 229DD
UT WOS:000325241100004
PM 23439383
ER
PT J
AU Lodge, D
Tidball, P
Mercier, MS
Lucas, SJ
Hanna, L
Ceolin, L
Kritikos, M
Fitzjohn, SM
Sherwood, JL
Bannister, N
Volianskis, A
Jane, DE
Bortolotto, ZA
Collingridge, GL
AF Lodge, David
Tidball, Patrick
Mercier, Marion S.
Lucas, Sarah J.
Hanna, Lydia
Ceolin, Laura
Kritikos, Minos
Fitzjohn, Stephen M.
Sherwood, John L.
Bannister, Neil
Volianskis, Arturas
Jane, David E.
Bortolotto, Zuner A.
Collingridge, Graham L.
TI Antagonists reversibly reverse chemical LTD induced by group I, group II
and group III metabotropic glutamate receptors
SO NEUROPHARMACOLOGY
LA English
DT Article
DE Metabotropic glutamate receptors; mGlul; mGlu2; mGlu5; mGlu8; DHPG;
DCG-IV; Long-term depression
ID LONG-TERM DEPRESSION; PROTEIN-COUPLED RECEPTORS; EXCITATORY
SYNAPTIC-TRANSMISSION; AGONIST-INDUCED INTERNALIZATION; HIPPOCAMPAL CA1
REGION; RAT PREFRONTAL CORTEX; MGLUR-DEPENDENT LTD; DHPG-INDUCED LTD;
MOSSY FIBER LTD; DENTATE GYRUS
AB Metabotropic glutamate (mGlu) receptors are implicated in many neurological and psychiatric diseases and are the targets of therapeutic agents currently in clinical development. Their activation has diverse effects in the central nervous system (CNS) that includes an involvement in synaptic plasticity. We previously reported that the brief exposure of hippocampal slices to dihydroxyphenylglycine (DHPG) can result in a long-term depression (LTD) of excitatory synaptic transmission. Surprisingly, this LTD could be fully reversed by mGlu receptor antagonists in a manner that was itself fully reversible upon washout of the antagonist. Here, 15 years after the discovery of DHPG-LTD and its reversible reversibility, we summarise these initial findings. We then present new data on DHPG-LTD, which demonstrates that evoked epileptiform activity triggered by activation of group I mGlu receptors can also be reversibly reversed by mGlu receptor antagonists. Furthermore, we show that the phenomenon of reversible reversibility is not specific to group I mGlu receptors. We report that activation of group II mGlu receptors in the temporo-ammonic pathway (TAP) and mossy fibre pathway within the hippocampus and in the cortical input to neurons of the lateral amygdala induces an LTD that is reversed by LY341495, a group II mGlu receptor antagonist. We also show that activation of group III mGlu8 receptors induces an LTD at lateral perforant path inputs to the dentate gyrus and that this LTD is reversed by MDCPG, an mGlu8 receptor antagonist. In conclusion, we have shown that activation of representative members of each of the three groups of mGlu receptors can induce forms of LTD than can be reversed by antagonists, and that in each case washout of the antagonist is associated with the re-establishment of the LTD.
This article is part of the Special Issue entitled 'Glutamate Receptor-Dependent Synaptic Plasticity'. (C) 2013 Elsevier Ltd. All rights reserved.
C1 [Lodge, David; Tidball, Patrick; Mercier, Marion S.; Lucas, Sarah J.; Hanna, Lydia; Ceolin, Laura; Kritikos, Minos; Fitzjohn, Stephen M.; Sherwood, John L.; Bannister, Neil; Volianskis, Arturas; Jane, David E.; Bortolotto, Zuner A.; Collingridge, Graham L.] Univ Bristol, Sch Physiol & Pharmacol, Ctr Synapt Plast, Bristol BS1 3NY, Avon, England.
[Lucas, Sarah J.] NIEHS, Neurobiol Lab, Res Triangle Pk, NC 27709 USA.
[Ceolin, Laura] Univ Montpellier 2, Univ Montpellier 1, INSERM U661, Inst Funct Genom,CNRS UMR5203, F-34000 Montpellier, France.
[Fitzjohn, Stephen M.; Sherwood, John L.] Eli Lilly & Co, Lilly Res Ctr, Neurosci Res Div, Erl Wood Manor, Windlesham GU20 6PH, Surrey, England.
[Collingridge, Graham L.] Seoul Natl Univ, Coll Nat Sci, Dept Brain & Cognit Sci, Seoul 151746, South Korea.
RP Lodge, D (reprint author), Univ Bristol, Sch Physiol & Pharmacol, Ctr Synapt Plast, Dorothy Hodgkin Bldg, Bristol BS1 3NY, Avon, England.
EM David.Lodge@Bristol.ac.uk
RI Collingridge, Graham/C-4605-2015;
OI Collingridge, Graham/0000-0002-9572-5359; Sherwood,
John/0000-0002-8484-1100; Fitzjohn, Stephen/0000-0002-3859-7530; Lucas,
Sarah/0000-0002-5577-763X
FU Eli Lilly; BBSRC; MRC; Wellcome Trust; WCU Program (Republic of Korea)
FX This work was supported by Eli Lilly, BBSRC, MRC and Wellcome Trust (all
UK) and the WCU Program (Republic of Korea).
NR 108
TC 12
Z9 12
U1 0
U2 19
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0028-3908
J9 NEUROPHARMACOLOGY
JI Neuropharmacology
PD NOV
PY 2013
VL 74
SI SI
BP 135
EP 146
DI 10.1016/j.neuropharm.2013.03.011
PG 12
WC Neurosciences; Pharmacology & Pharmacy
SC Neurosciences & Neurology; Pharmacology & Pharmacy
GA 229DD
UT WOS:000325241100017
PM 23542080
ER
PT J
AU Darnell, MC
Sun, JY
Mehta, M
Johnson, C
Arany, PR
Suo, ZG
Mooney, DJ
AF Darnell, Max C.
Sun, Jeong-Yun
Mehta, Manav
Johnson, Christopher
Arany, Praveen R.
Suo, Zhigang
Mooney, David J.
TI Performance and biocompatibility of extremely tough
alginate/polyacrylamide hydrogels
SO BIOMATERIALS
LA English
DT Article
DE Biocompatibility; Hydrogel; Mechanical properties; Tendon prosthesis
ID IN-VITRO BIOCOMPATIBILITY; POLYACRYLAMIDE HYDROGELS; DEGRADATION;
ACRYLAMIDE; BIOMATERIALS; OXIDATION; CARTILAGE; STRENGTH; RELEASE; CELLS
AB Although hydrogels now see widespread use in a host of applications, low fracture toughness and brittleness have limited their more broad use. As a recently described interpenetrating network (IPN) of alginate and polyacrylamide demonstrated a fracture toughness of similar to 9000 J/m(2), we sought to explore the biocompatibility and maintenance of mechanical properties of these hydrogels in cell culture and in vivo conditions. These hydrogels can sustain a compressive strain of over 90% with minimal loss of Young's Modulus as well as minimal swelling for up to 50 days of soaking in culture conditions. Mouse mesenchymal stem cells exposed to the IPN gel-conditioned media maintain high viability, and although cells exposed to conditioned media demonstrate slight reductions in proliferation and metabolic activity (WST assay), these effects are abrogated in a dose-dependent manner. Implantation of these IPN hydrogels into subcutaneous tissue of rats for 8 weeks led to mild fibrotic encapsulation and minimal inflammatory response. These results suggest the further exploration of extremely tough alginate/PAAM IPN hydrogels as biomaterials. (c) 2013 Elsevier Ltd. All rights reserved.
C1 [Darnell, Max C.; Sun, Jeong-Yun; Mehta, Manav; Arany, Praveen R.; Suo, Zhigang; Mooney, David J.] Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA.
[Darnell, Max C.; Mehta, Manav; Johnson, Christopher; Arany, Praveen R.; Mooney, David J.] Harvard Univ, Wyss Inst Biol Inspired Engn, Cambridge, MA 02138 USA.
[Sun, Jeong-Yun; Suo, Zhigang] Kavli Inst Bionano Sci & Technol, Cambridge, MA 02138 USA.
[Arany, Praveen R.] Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20982 USA.
RP Mooney, DJ (reprint author), Harvard Univ, Sch Engn & Appl Sci, Cambridge, MA 02138 USA.
EM mooneyd@deas.harvard.edu
RI Suo, Zhigang/B-1067-2008
OI Suo, Zhigang/0000-0002-4068-4844
FU National Institutes of Health [R01 DE013349, R37 DEO013033]; intramural
research program of the NIDCR/NIH(PA)
FX The authors would like to thank Dr. Evi Lippens for helpful discussions
regarding the histology, and funding support from the National
Institutes of Health (R01 DE013349, R37 DEO013033). This research was
partially supported by the intramural research program of the NIDCR/NIH
(PA).
NR 24
TC 52
Z9 53
U1 20
U2 208
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0142-9612
J9 BIOMATERIALS
JI Biomaterials
PD NOV
PY 2013
VL 34
IS 33
BP 8042
EP 8048
DI 10.1016/j.biomaterials.2013.06.061
PG 7
WC Engineering, Biomedical; Materials Science, Biomaterials
SC Engineering; Materials Science
GA 222HB
UT WOS:000324720700004
PM 23896005
ER
PT J
AU Jaeger, AA
Das, CK
Morgan, NY
Pursley, RH
McQueen, PG
Hall, MD
Pohida, TJ
Gottesman, MM
AF Jaeger, Ashley A.
Das, Chandan K.
Morgan, Nicole Y.
Pursley, Randall H.
McQueen, Philip G.
Hall, Matthew D.
Pohida, Thomas J.
Gottesman, Michael M.
TI Microfabricated polymeric vessel mimetics for 3-D cancer cell culture
SO BIOMATERIALS
LA English
DT Article
DE Bioreactor; Silicone; Hydrogel; Microstructure; Oxygenation;
Carcinogenesis
ID BASEMENT-MEMBRANE MATRIX; EXTRACELLULAR-MATRIX; DRUG-RESISTANCE;
BREAST-CANCER; IN-VITRO; TUMOR MICROENVIRONMENT; BIOARTIFICIAL LIVER;
SPHEROID CULTURE; RAT HEPATOCYTES; GENE-EXPRESSION
AB Modeling tumor growth in vitro is essential for cost-effective testing of hypotheses in preclinical cancer research. 3-D cell culture offers an improvement over monolayer culture for studying cellular processes in cancer biology because of the preservation of cell cell and cell-ECM interactions. Oxygen transport poses a major barrier to mimicking in vivo environments and is not replicated in conventional cell culture systems. We hypothesized that we can better mimic the tumor microenvironment using a bioreactor system for controlling gas exchange in cancer cell cultures with silicone hydrogel synthetic vessels. Soft-lithography techniques were used to fabricate oxygen-permeable silicone hydrogel membranes containing arrays of micropillars. These membranes were inserted into a bioreactor and surrounded by basement membrane extract (BME) within which fluorescent ovarian cancer (OVCAR8) cells were cultured. Cell clusters oxygenated by synthetic vessels showed a similar to 100 mu m drop-off to anoxia, consistent with in vivo studies of tumor nodules fed by the microvasculature. Oxygen transport in the bioreactor system was characterized by experimental testing with a dissolved oxygen probe and finite element modeling of convective flow. Our study demonstrates differing growth patterns associated with controlling gas distributions to better mimic in vivo conditions. Published by Elsevier Ltd.
C1 [Jaeger, Ashley A.; Das, Chandan K.; Hall, Matthew D.; Gottesman, Michael M.] NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA.
[Jaeger, Ashley A.; Pursley, Randall H.; McQueen, Philip G.; Pohida, Thomas J.] NIH, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA.
[Morgan, Nicole Y.] Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD USA.
RP Gottesman, MM (reprint author), NCI, Cell Biol Lab, NIH, Bldg 37, Bethesda, MD 20892 USA.
EM mgottesman@nih.gov
FU Intramural Research Program of the NIH; National Cancer Institute;
Center for Information Technology; National Institute of Biomedical
Imaging and Bioengineering
FX This work was supported by the Intramural Research Program of the NIH,
the National Cancer Institute, the Center for Information Technology,
and the National Institute of Biomedical Imaging and Bioengineering.
NR 68
TC 7
Z9 7
U1 1
U2 55
PU ELSEVIER SCI LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND
SN 0142-9612
J9 BIOMATERIALS
JI Biomaterials
PD NOV
PY 2013
VL 34
IS 33
BP 8301
EP 8313
DI 10.1016/j.biomaterials.2013.07.013
PG 13
WC Engineering, Biomedical; Materials Science, Biomaterials
SC Engineering; Materials Science
GA 222HB
UT WOS:000324720700029
PM 23911071
ER
PT J
AU Valente, AJ
Sakamuri, SSVP
Siddesha, JM
Yoshida, T
Gardner, JD
Prabhu, R
Siebenlist, U
Chandrasekar, B
AF Valente, Anthony J.
Sakamuri, Siva S. V. P.
Siddesha, Jalahalli M.
Yoshida, Tadashi
Gardner, Jason D.
Prabhu, Ramesh
Siebenlist, Ulrich
Chandrasekar, Bysani
TI TRAF3IP2 mediates interleukin-18-induced cardiac fibroblast migration
and differentiation
SO CELLULAR SIGNALLING
LA English
DT Article
DE RNA interference; Cardiac fibroblasts; Migration; TRAF3IP2; Cardiac
fibrosis; Remodeling
ID NF-KAPPA-B; GROWTH-FACTOR; TRANSCRIPTION FACTORS; CIKS ACT1; IN-VIVO;
EXPRESSION; CELL; PROTEIN; INFLAMMATION; ACTIVATION
AB TRAF3IP2 is a cytoplasmic adapter protein and an upstream regulator of IKK/NF-kappa B and JNK/AP-1. Here we demonstrate for the first time that the proinflammatory cytokine interleukin (IL)-18 induces TRAF3IP2 expression in primary cardiac fibroblasts (CF) in a Nox4/hydrogen peroxide-dependent manner. Silencing TRAF3IP2 using a phosphorothioated, 2'-O-methyl modified, cholesterol-tagged TRAF3IP2 siRNA duplex markedly attenuated IL-18-induced NF-kappa B and AP-1 activation and CF migration. Using co-IP/IB and co-localization experiments, we show that Nox4 physically associates with IL-18 receptor proteins, and IL-18 enhances their binding. Further, IL-18 promotes fibroblast to myofibroblast transition, as evidenced by enhanced a-smooth muscle actin expression, types 1 and 3 collagen induction, and soluble collagen secretion, via TRAF3IP2. These results indicate that TRAF3IP2 is a critical intermediate in IL-18-induced CF migration and differentiation in vitro. TRAF3IP2 could serve as a potential therapeutic target in cardiac fibrosis and adverse remodeling in vivo. (C) 2013 Elsevier Inc. All rights reserved.
C1 [Valente, Anthony J.] Univ Texas Hlth Sci Ctr San Antonio, San Antonio, TX 78229 USA.
[Valente, Anthony J.] South Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA.
[Sakamuri, Siva S. V. P.; Siddesha, Jalahalli M.; Yoshida, Tadashi; Chandrasekar, Bysani] Tulane Univ, Sch Med, Inst Heart & Vasc, New Orleans, LA 70112 USA.
[Gardner, Jason D.] Louisiana State Univ, Hlth Sci Ctr, New Orleans, LA 70112 USA.
[Prabhu, Ramesh] Tulane Univ, Sch Med, New Orleans, LA 70112 USA.
[Siebenlist, Ulrich] NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA.
[Chandrasekar, Bysani] Southeast Louisiana Vet Hlth Care Syst, Res Serv, New Orleans, LA 70161 USA.
RP Chandrasekar, B (reprint author), Tulane Univ, Sch Med, Inst Heart & Vasc, 1430 Tulane Ave, New Orleans, LA 70112 USA.
EM bchandra@tulane.edu
OI Yoshida, Tadashi/0000-0002-4544-1497
FU Department of Veterans Affairs Research Career Scientist award; VA
Office of Research and Development Biomedical Laboratory Research and
Development Service Award [1IO1BX000246]; NIH/NHLBI [HL-86787]
FX BC is a recipient of the Department of Veterans Affairs Research Career
Scientist award, and is supported by VA Office of Research and
Development Biomedical Laboratory Research and Development Service Award
1IO1BX000246 and the NIH/NHLBI grant HL-86787. The contents of this
report do not represent the views of the Department of Veterans Affairs
or the United States Government
NR 30
TC 18
Z9 19
U1 0
U2 6
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0898-6568
J9 CELL SIGNAL
JI Cell. Signal.
PD NOV
PY 2013
VL 25
IS 11
BP 2176
EP 2184
DI 10.1016/j.cellsig.2013.07.013
PG 9
WC Cell Biology
SC Cell Biology
GA 225OI
UT WOS:000324971800011
PM 23872479
ER
PT J
AU Lin, YC
Tsai, JY
Yang, JS
Lee, YH
Hamel, E
Lee, KH
Kuo, SC
Huang, LJ
AF Lin, Yi-Chien
Tsai, Jui-Ying
Yang, Jai-Sing
Lee, Yueh-Hsuan
Hamel, Ernest
Lee, Kuo-Hsiung
Kuo, Sheng-Chu
Huang, Li-Jiau
TI The novel synthetic compound
6-acetyl-9-(3,4,5-trimethoxybenzyl)-9H-pyrido[2,3-b]indole induces
mitotic arrest and apoptosis in human COLO 205 cells
SO INTERNATIONAL JOURNAL OF ONCOLOGY
LA English
DT Article
DE 6-acetyl-9-(3,4,5-trimethoxybenzyl)-9H-pyrido[2,3-b]indole;
alpha-caboline derivative; human colon carcinoma COLO 205; mitotic
arrest; apoptosis; aurora kinase
ID AURORA-KINASE INHIBITORS; CANCER-THERAPY; COLORECTAL-CANCER; ANTICANCER
AGENTS; BCL-2 FAMILY; PATHWAYS; GROWTH; BAX; MECHANISMS; PROTEINS
AB A novel synthetic compound 6-acetyl-9-(3,4,5-trimethoxybenzyl)-9H-pyrido[2,3-b]indole (HAC-Y6) demonstrated selective anticancer activity. In the present study, COLO 205 cells were treated with HAC-Y6 to investigate the molecular mechanisms underlying its effects. HAC-Y6 induced growth inhibition, G(2)/M arrest and apoptosis in COLO 205 cells with an IC50 of 0.52 +/- 0.035 mu M. Annexin V/PI double staining demonstrated the presence of apoptotic cells. JC-1 staining analysis showed that HAC-Y6 decreased mitochondrial membrane potential in support of apoptosis. An immunostaining assay revealed that HAC-Y6 depolymerized microtubules. Treatment of COLO 205 cells with HAC-Y6 resulted in increased expression of BubR1 and cyclin B1 and decreased expression of aurora A, phospho-aurora A, aurora B, phospho-aurora B and phospho-H3. HAC-Y6 treatment increased protein levels of active caspase-3, caspase-9, Endo G, AIF, Apaf-1, cytochrome c and Bax, but treatment with the compound caused reduced levels of procaspase-3, procaspase-9, Bcl-xL and Bcl-2. Overall, our results suggest that HAC-Y6 exerts anticancer effects by disrupting microtubule assembly and inducing G(2)/M arrest, polyploidy and apoptosis via mitochondrial pathways in COLO 205 cells.
C1 [Lin, Yi-Chien; Tsai, Jui-Ying; Lee, Yueh-Hsuan; Kuo, Sheng-Chu; Huang, Li-Jiau] China Med Univ, Grad Inst Pharmaceut Chem, Taichung 40402, Taiwan.
[Yang, Jai-Sing] China Med Univ, Dept Pharmacol, Taichung 40402, Taiwan.
[Hamel, Ernest] NCI, Screening Technol Branch, Dev Therapeut Program, Div Canc Treatment & Diag,NIH, Frederick, MD 21702 USA.
[Lee, Kuo-Hsiung] Univ N Carolina, Nat Prod Res Labs, Eshelman Sch Pharm, Chapel Hill, NC 27599 USA.
[Lee, Kuo-Hsiung] China Med Univ Hosp, Chinese Med Res & Dev Ctr, Taichung 40402, Taiwan.
RP Huang, LJ (reprint author), China Med Univ, Grad Inst Pharmaceut Chem, 91 Hsueh Shih Rd, Taichung 40402, Taiwan.
EM ljhuang@mail.cmu.edu.tw
RI Yang, Jai Sing/M-1162-2015
FU National Science Council of the Republic of China [NSC
98-2628-B-039-018-MY3]
FX This study was supported by a research grant from the National Science
Council of the Republic of China, awarded to L.-J.H. (NSC
98-2628-B-039-018-MY3). Experiments and data analysis were performed, in
part, through the use of the Medical Research Core Facilities Center,
Office of Research and Development, China Medical University, Taichung,
Taiwan, R.O.C.
NR 44
TC 3
Z9 3
U1 0
U2 10
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 2013
VL 43
IS 5
BP 1596
EP 1606
DI 10.3892/ijo.2013.2069
PG 11
WC Oncology
SC Oncology
GA 225SN
UT WOS:000324982700031
PM 23970288
ER
PT J
AU Wood, AC
Maris, JM
Gorlick, R
Kolb, EA
Keir, ST
Reynolds, CP
Kang, MH
Wu, JR
Kurmasheva, RT
Whiteman, K
Houghton, PJ
Smith, MA
AF Wood, Andrew C.
Maris, John M.
Gorlick, Richard
Kolb, E. Anders
Keir, Stephen T.
Reynolds, C. Patrick
Kang, Min H.
Wu, Jianrong
Kurmasheva, Raushan T.
Whiteman, Kathleen
Houghton, Peter J.
Smith, Malcolm A.
TI Initial Testing (Stage 1) of the Antibody-Maytansinoid Conjugate,
IMGN901 (Lorvotuzumab Mertansine), by the Pediatric Preclinical Testing
Program
SO PEDIATRIC BLOOD & CANCER
LA English
DT Article
DE antibody-maytansinoid conjugate; developmental therapeutics;
microtubules; preclinical testing
ID CELL-ADHESION MOLECULE; TUMOR XENOGRAFTS; DRUG CONJUGATE; USEFUL MARKER;
PHASE-I; CANCER; CD56; EXPRESSION; COMBINATION; RHABDOMYOSARCOMA
AB BackgroundIMGN901 (lorvotuzumab mertansine) is an antibody-drug conjugate composed of a humanized antibody that specifically binds to CD56 (NCAM, neural cell adhesion molecule) and that is conjugated to the maytansinoid, DM1 (a microtubule targeting agent).
ProceduresIMGN901 and DM1-SMe (unconjugated DM1 as a mixed disulfide with thiomethane to cap its sulfhydryl group) were tested in vitro at concentrations ranging from 0.01nM to 0.1 mu M and 0.3pM to 3nM, respectively. IMGN901 was tested against a subset of PPTP solid tumor xenografts focusing on those with high CD56 expression.The combination of IMGN901 with topotecan was also evaluated.
ResultsNeuroblastoma models expressed CD56 at or above the median expression level for all PPTP xenografts and cell lines. Neuroblastoma cell lines demonstrated relatively low sensitivity to DM1-SMe compared to other cell lines, but the sensitivity of neuroblastoma cell lines to IMGN901 was comparable to that of non-neuroblastoma cell lines. In vivo, objective responses were observed in 9 of 24 (38%) models including, three of seven neuroblastoma xenografts, and two of seven rhabdomyosarcoma xenografts. All xenografts with objective responses showed homogeneous high-level staining by IHC for CD56, but not all xenografts with homogenous high-level staining had objective responses. Combined with topotecan, IMGN901 demonstrated therapeutic enhancement against two of four neuroblastoma models.
ConclusionsIMGN901 has anti-tumor activity against some CD56 expressing pediatric cancer models. High expression of CD56 is a biomarker for in vivo response, but resistance mechanisms to IMGN901 in some high CD56 expressing lines need to be defined. Pediatr Blood Cancer 2013;60:1860-1867. (c) 2013 Wiley Periodicals, Inc.
C1 [Wood, Andrew C.; Maris, John M.] Univ Penn, Childrens Hosp Philadelphia, Sch Med, Hematol Oncol Div Oncol, Philadelphia, PA 19104 USA.
[Wood, Andrew C.; Maris, John M.] Abramson Family Canc Res Inst, Philadelphia, PA USA.
[Gorlick, Richard] Childrens Hosp Montefiore, Bronx, NY USA.
[Kolb, E. Anders] Alfred I DuPont Hosp Children, Wilmington, DE USA.
[Keir, Stephen T.] Duke Univ, Med Ctr, Durham, NC USA.
[Reynolds, C. Patrick; Kang, Min H.] Texas Tech Univ, Hlth Sci Ctr, Lubbock, TX 79430 USA.
[Wu, Jianrong] St Jude Childrens Res Hosp, Memphis, TN 38105 USA.
[Kurmasheva, Raushan T.; Houghton, Peter J.] Nationwide Childrens Hosp, Columbus, OH USA.
[Whiteman, Kathleen] ImmunoGen Inc, Waltham, MD USA.
[Smith, Malcolm A.] NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA.
RP Maris, JM (reprint author), Childrens Hosp Philadelphia, Hematol Oncol Div Oncol, 3615 Civ Ctr Blvd,CTRB 3060, Philadelphia, PA 19104 USA.
EM maris@chop.edu
OI Reynolds, C. Patrick/0000-0002-2827-8536
FU National Cancer Institute [NO1-CM-42216, CM91001-03, CA21765, CA108786];
ImmunoGen, Inc.
FX Grant sponsor: National Cancer Institute; Grant numbers: NO1-CM-42216,
CM91001-03, CA21765, CA108786; Grant sponsor: Robert Lutz of ImmunoGen,
Inc.
NR 43
TC 7
Z9 7
U1 0
U2 9
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1545-5009
J9 PEDIATR BLOOD CANCER
JI Pediatr. Blood Cancer
PD NOV
PY 2013
VL 60
IS 11
BP 1860
EP 1867
DI 10.1002/pbc.24647
PG 8
WC Oncology; Hematology; Pediatrics
SC Oncology; Hematology; Pediatrics
GA 216QU
UT WOS:000324299800029
PM 23798344
ER
PT J
AU Cheng, J
Zhen, YY
Miksys, S
Beyoglu, D
Krausz, KW
Tyndale, RF
Yu, AM
Idle, JR
Gonzalez, FJ
AF Cheng, Jie
Zhen, Yueying
Miksys, Sharon
Beyoglu, Diren
Krausz, Kristopher W.
Tyndale, Rachel F.
Yu, Aiming
Idle, Jeffrey R.
Gonzalez, Frank J.
TI Potential role of CYP2D6 in the central nervous system
SO XENOBIOTICA
LA English
DT Article
DE Anxiety; brain; CYP2D6; serotonin
ID HARMALINE-INDUCED TREMOR; MONOXIDE-BINDING PIGMENT; HUMANIZED MOUSE
MODEL; FORCED SWIMMING TEST; CYTOCHROME-P450 2D6; DEBRISOQUINE SULFATE;
CEREBROSPINAL-FLUID; LIVER MICROSOMES; DRUG-METABOLISM; HUMAN BRAIN
AB 1. Cytochrome P450 2D6 (CYP2D6) is a pivotal enzyme responsible for a major drug oxidation polymorphism in human populations. Distribution of CYP2D6 in brain and its role in serotonin metabolism suggest that CYP2D6 may have a function in the central nervous system.
2. To establish an efficient and accurate platform for the study of CYP2D6 in vivo, a human CYP2D6 (Tg-2D6) model was generated by transgenesis in wild-type (WT) C57BL/6 mice using a P1 phage artificial chromosome clone containing the complete human CYP2D locus, including the CYP2D6 gene and 5'- and 3'-flanking sequences.
3. Human CYP2D6 was expressed not only in the liver but also in the brain. The abundance of serotonin and 5-hydroxyindoleacetic acid in brain of Tg-2D6 is higher than in WT mice, either basal levels or after harmaline induction. Metabolomics of brain homogenate and cerebrospinal fluid revealed a significant up-regulation of L-carnitine, acetyl-L-carnitine, pantothenic acid, 2'-deoxycytidine diphosphate (dCDP), anandamide, N-acetylglucosaminylamine and a down-regulation of stearoyl-L-carnitine in Tg-2D6 mice compared with WT mice. Anxiety tests indicate Tg-2D6 mice have a higher capability to adapt to anxiety.
4. Overall, these findings indicate that the Tg-2D6 mouse model may serve as a valuable in vivo tool to determine CYP2D6-involved neurophysiological metabolism and function.
C1 [Cheng, Jie; Zhen, Yueying; Krausz, Kristopher W.; Gonzalez, Frank J.] NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Miksys, Sharon; Tyndale, Rachel F.] Univ Toronto, Dept Pharmacol & Toxicol, Ctr Addict & Mental Hlth, Toronto, ON, Canada.
[Miksys, Sharon; Tyndale, Rachel F.] Univ Toronto, Dept Psychiat, Ctr Addict & Mental Hlth, Toronto, ON, Canada.
[Beyoglu, Diren; Idle, Jeffrey R.] Univ Bern, Dept Clin Res, Hepatol Res Grp, Bern, Switzerland.
[Yu, Aiming] SUNY Buffalo, Dept Pharmaceut Sci, Buffalo, NY 14260 USA.
RP Gonzalez, FJ (reprint author), NCI, Lab Metab, Ctr Canc Res, Bldg 37,Room 3106, Bethesda, MD 20892 USA.
EM fjgonz@helix.nih.gov
OI Idle, Jeff/0000-0002-6143-1520
FU National Cancer Institute Intramural Research Program; CIHR [MOP97751];
CAMH; Canada Foundation for Innovation [20289, 16014]; CAMH Foundation;
Ontario Ministry of Research and Innovation
FX This study was supported by the National Cancer Institute Intramural
Research Program, a CIHR grant MOP97751, CAMH and the Canada Foundation
for Innovation (#20289 and #16014), the CAMH Foundation and the Ontario
Ministry of Research and Innovation.
NR 63
TC 17
Z9 19
U1 1
U2 18
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 0049-8254
J9 XENOBIOTICA
JI Xenobiotica
PD NOV
PY 2013
VL 43
IS 11
BP 973
EP 984
DI 10.3109/00498254.2013.791410
PG 12
WC Pharmacology & Pharmacy; Toxicology
SC Pharmacology & Pharmacy; Toxicology
GA 227GN
UT WOS:000325099600005
PM 23614566
ER
PT J
AU Hong, SP
Fuciarelli, AF
Johnson, JD
Graves, SW
Bates, DJ
Smith, CS
Waidyanatha, S
AF Hong, S. Peter
Fuciarelli, Alfred F.
Johnson, Jerry D.
Graves, Steven W.
Bates, Derrick J.
Smith, Cynthia S.
Waidyanatha, Suramya
TI Toxicokinetics of Isoeugenol in F344 rats and B6C3F(1) mice
SO XENOBIOTICA
LA English
DT Article
DE Bioavailability; Isoeugenol; toxicokinetics
ID FISCHER-344 RAT; METABOLISM; SAFROLE; PHARMACOKINETICS; METHYLEUGENOL;
CONSTITUENTS; DERIVATIVES; INDUCTION; TOXICITY; MOUSE
AB 1. Isoeugenol (IEG) has been tested for toxicity and carcinogenicity due to high potential for human exposure and the structural resemblance to known carcinogenic allylbenzenes. In order to support the interpretation of toxicity and carcinogenecity study outcomes, a toxicokinetic study was performed in which both sexes of F344 rats and B6C3F(1) mice were given IEG as a single intravenous (IV) or gavage administration.
2. Following IV administration, IEG was rapidly eliminated from systemic circulation in both species and sexes. Gavage administration revealed a rapid absorption of IEG with t(max) values <= 20 min for both species and sexes. In rats, AUC increased in a greater than dose-proportional manner and Cl-app values decreased with increasing dose in both sexes suggesting saturation of IEG metabolism. On the other hand, Cl-app values in male mice increased with increasing dose suggesting induction of IEG metabolism although this was not evident in the females.
3. Absolute bioavailability was greater in female rats (19%) than male rats (10%) (p < 0.0001), but was not different between the sexes for mice (28% males; 31% females) (p = 0.2437). The collective toxicokinetic data supported that low bioavailability following administration of IEG was the result of extensive first-pass metabolism.
C1 [Hong, S. Peter; Johnson, Jerry D.; Graves, Steven W.] Battelle Mem Inst, Columbus, OH 43201 USA.
[Fuciarelli, Alfred F.] Valdosta State Univ, Valdosta, GA USA.
[Bates, Derrick J.] Pacific NW Natl Lab, Richland, WA 99352 USA.
[Smith, Cynthia S.; Waidyanatha, Suramya] NIEHS, Res Triangle Pk, NC 27709 USA.
RP Hong, SP (reprint author), Battelle Mem Inst, 505 King Ave, Columbus, OH 43201 USA.
EM hongs@battelle.org
NR 32
TC 2
Z9 2
U1 2
U2 12
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 0049-8254
J9 XENOBIOTICA
JI Xenobiotica
PD NOV
PY 2013
VL 43
IS 11
BP 1010
EP 1017
DI 10.3109/00498254.2013.790576
PG 8
WC Pharmacology & Pharmacy; Toxicology
SC Pharmacology & Pharmacy; Toxicology
GA 227GN
UT WOS:000325099600008
PM 23627552
ER
PT J
AU Zoico, E
Corzato, F
Bambace, C
Rossi, AP
Micciolo, R
Cinti, S
Harris, TB
Zamboni, M
AF Zoico, Elena
Corzato, Francesca
Bambace, Clara
Rossi, Andrea P.
Micciolo, Rocco
Cinti, Saverio
Harris, Tamara B.
Zamboni, Mauro
TI Myosteatosis and myofibrosis: Relationship with aging, inflammation and
insulin resistance
SO ARCHIVES OF GERONTOLOGY AND GERIATRICS
LA English
DT Article
DE Muscle quality; Fat infiltration; Fibrosis; Aging
ID ADIPOSE-TISSUE INFILTRATION; SKELETAL-MUSCLE; BODY-COMPOSITION;
SARCOPENIA; STRENGTH; FIBROSIS; ACTIVATION; MYOSTATIN; THERAPY; HEALTH
AB The mechanisms impairing muscle quality and leading to myofibrosis (MF) and myosteatosis (MS) are incompletely known. In biopsies of paraspinous muscle (PM) of 16 elderly men undergoing elective vertebral surgery, we histologically determined the area of MF and MS expressed as muscle quality index (MQI), in order to investigate the relation between them, as well as the main predictors of muscle quality. Total PM area and intermuscular adipose tissue (IMAT) were evaluated by MRI and body composition by DXA. Circulating fasting glucose, insulin, hs-CRP, leptin, adiponectin and IL-6 were measured and HOMA index calculated. Quantification of gene expression in PM and in subcutaneous adipose tissue (SAT) overlying the muscle was performed by rt-PCR. The degree of MS and MF was significantly and positively related to each other and positively associated with BMI, waist, FM and FM% as well as with IMAT. The area of PM was negatively related with MF even after adjustment for weight. Leptin was positively associated with MF and MS, whereas hs-CRP to MF. In backward regression analyses, larger waist and smaller PM area explained 90% of MF variance, whereas leptin about 80% of MS variance. IL-6 expression in SAT was significantly higher in participants with higher MQI values. In PM biopsies we found significantly higher expression of SOCS-3 and a trend toward higher expression of myostatin with greater degrees of MQI. MS and MF are related phenomena that concur to alter muscle quality and both should be considered in further studies on the evolution of sarcopenia. (C) 2013 Elsevier Ireland Ltd. All rights reserved.
C1 [Zoico, Elena; Corzato, Francesca; Bambace, Clara; Rossi, Andrea P.; Zamboni, Mauro] Univ Verona, Div Geriatr Med, I-37126 Verona, Italy.
[Micciolo, Rocco] Univ Trento, Fac Sociol, Trento, Italy.
[Cinti, Saverio] Univ Ancona, Inst Normal Human Morphol, Ancona, Italy.
[Harris, Tamara B.] NIA, Lab Epidemiol Demog & Biometry, Interdisciplinary Studies Aging Sect, Bethesda, MD 20892 USA.
RP Zoico, E (reprint author), Univ Verona, Div Geriatr Med, Osped Maggiore, Ple A Stefani 1, I-37126 Verona, Italy.
EM elena.zoico@univr.it
OI ZAMBONI, Mauro/0000-0001-6961-9483; ZOICO, Elena/0000-0002-5235-1545
FU Intramural NIH HHS [ZIA AG004050-05]
NR 27
TC 11
Z9 11
U1 1
U2 24
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0167-4943
J9 ARCH GERONTOL GERIAT
JI Arch. Gerontol. Geriatr.
PD NOV-DEC
PY 2013
VL 57
IS 3
BP 411
EP 416
DI 10.1016/j.archger.2013.06.001
PG 6
WC Geriatrics & Gerontology
SC Geriatrics & Gerontology
GA 213AE
UT WOS:000324024300026
PM 23809667
ER
EF