FN Thomson Reuters Web of Science™
VR 1.0
PT J
AU Brown, D
Sloan, J
Manoli, I
Venditti, CP
AF Brown, Donna
Sloan, Jennifer
Manoli, Irini
Venditti, Charles P.
TI Three pregnancies complicated by methylmalonic acidemia (MMA) and
cesarean deliveries
SO MOLECULAR GENETICS AND METABOLISM
LA English
DT Meeting Abstract
CT 35th Annual Meeting of the Society-for-Inherited-Metabolic-Disorders
(SIMD)
CY MAR 31-APR 03, 2012
CL Charlotte, NC
SP Soc Inherited Metabol Disorders (SIMD), Abbott Nutr (Abbott Metabol), Pfizer Inc, Shire, Actel Pharmaceut (ACTELION), Cytonet LLC, GeneDx, Genzyme, Hyper Therapeut, Inc, Mead Johnson Nutr, Orphan Europe Recordati Grp, Rare Dis Therapeut, Inc, Ucyclyd Pharma, Vitaflo, Appl Nutr Corp, ARUP Labs, BioMarin Pharmaceut, Inc, Cambrooke Foods, Inc, Emory Genet Lab, Hitachi High Technol Amer, Inc, Prevent Genet, Transgenom, Inc, Canadian PKU & Allied Disorders Inc, Natl PKU Alliance, Natl Urea Cycle Disorders Fdn, Propion Acidemia Fdn, United Mitochondrial Dis Fdn
C1 [Brown, Donna; Sloan, Jennifer; Manoli, Irini; Venditti, Charles P.] NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA.
[Brown, Donna] Washington Hosp Ctr, Dept Obstet & Gynecol, Washington, DC 20010 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1096-7192
J9 MOL GENET METAB
JI Mol. Genet. Metab.
PD MAR
PY 2012
VL 105
IS 3
BP 306
EP 306
PG 1
WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research &
Experimental
SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental
Medicine
GA 913VV
UT WOS:000301906400047
ER
PT J
AU Camp, KM
Lloyd-Puryear, MA
Coates, PM
Groft, SC
AF Camp, K. M.
Lloyd-Puryear, M. A.
Coates, P. M.
Groft, S. C.
TI Nutrition and dietary supplement interventions for inborn errors of
metabolism: Building a framework for evidence-based research results of
a stakeholder workshop
SO MOLECULAR GENETICS AND METABOLISM
LA English
DT Meeting Abstract
CT 35th Annual Meeting of the Society-for-Inherited-Metabolic-Disorders
(SIMD)
CY MAR 31-APR 03, 2012
CL Charlotte, NC
SP Soc Inherited Metabol Disorders (SIMD), Abbott Nutr (Abbott Metabol), Pfizer Inc, Shire, Actel Pharmaceut (ACTELION), Cytonet LLC, GeneDx, Genzyme, Hyper Therapeut, Inc, Mead Johnson Nutr, Orphan Europe Recordati Grp, Rare Dis Therapeut, Inc, Ucyclyd Pharma, Vitaflo, Appl Nutr Corp, ARUP Labs, BioMarin Pharmaceut, Inc, Cambrooke Foods, Inc, Emory Genet Lab, Hitachi High Technol Amer, Inc, Prevent Genet, Transgenom, Inc, Canadian PKU & Allied Disorders Inc, Natl PKU Alliance, Natl Urea Cycle Disorders Fdn, Propion Acidemia Fdn, United Mitochondrial Dis Fdn
C1 [Camp, K. M.; Coates, P. M.] NIH, Off Dietary Supplements, Bethesda, MD 20892 USA.
[Lloyd-Puryear, M. A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA.
[Groft, S. C.] NIH, Off Rare Dis Res, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1096-7192
J9 MOL GENET METAB
JI Mol. Genet. Metab.
PD MAR
PY 2012
VL 105
IS 3
BP 308
EP 308
PG 1
WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research &
Experimental
SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental
Medicine
GA 913VV
UT WOS:000301906400050
ER
PT J
AU Estrada-Veras, J
Manoli, I
Sloan, J
Venditti, CP
AF Estrada-Veras, Juvianee
Manoli, Irini
Sloan, Jennifer
Venditti, C. P.
TI Central line sepsis caused by mycobacterium fortuitum in methylmalonic
acidemia (MMA)
SO MOLECULAR GENETICS AND METABOLISM
LA English
DT Meeting Abstract
CT 35th Annual Meeting of the Society-for-Inherited-Metabolic-Disorders
(SIMD)
CY MAR 31-APR 03, 2012
CL Charlotte, NC
SP Soc Inherited Metabol Disorders (SIMD), Abbott Nutr (Abbott Metabol), Pfizer Inc, Shire, Actel Pharmaceut (ACTELION), Cytonet LLC, GeneDx, Genzyme, Hyper Therapeut, Inc, Mead Johnson Nutr, Orphan Europe Recordati Grp, Rare Dis Therapeut, Inc, Ucyclyd Pharma, Vitaflo, Appl Nutr Corp, ARUP Labs, BioMarin Pharmaceut, Inc, Cambrooke Foods, Inc, Emory Genet Lab, Hitachi High Technol Amer, Inc, Prevent Genet, Transgenom, Inc, Canadian PKU & Allied Disorders Inc, Natl PKU Alliance, Natl Urea Cycle Disorders Fdn, Propion Acidemia Fdn, United Mitochondrial Dis Fdn
C1 [Manoli, Irini; Sloan, Jennifer; Venditti, C. P.] NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1096-7192
J9 MOL GENET METAB
JI Mol. Genet. Metab.
PD MAR
PY 2012
VL 105
IS 3
BP 316
EP 317
PG 2
WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research &
Experimental
SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental
Medicine
GA 913VV
UT WOS:000301906400065
ER
PT J
AU Estrada-Veras, J
Gahl, W
Gochuico, B
AF Estrada-Veras, Juvianee
Gahl, William
Gochuico, Bernadette
TI Erdheim Chester Disease (ECD): Presentation and natural history
SO MOLECULAR GENETICS AND METABOLISM
LA English
DT Meeting Abstract
CT 35th Annual Meeting of the Society-for-Inherited-Metabolic-Disorders
(SIMD)
CY MAR 31-APR 03, 2012
CL Charlotte, NC
SP Soc Inherited Metabol Disorders (SIMD), Abbott Nutr (Abbott Metabol), Pfizer Inc, Shire, Actel Pharmaceut (ACTELION), Cytonet LLC, GeneDx, Genzyme, Hyper Therapeut, Inc, Mead Johnson Nutr, Orphan Europe Recordati Grp, Rare Dis Therapeut, Inc, Ucyclyd Pharma, Vitaflo, Appl Nutr Corp, ARUP Labs, BioMarin Pharmaceut, Inc, Cambrooke Foods, Inc, Emory Genet Lab, Hitachi High Technol Amer, Inc, Prevent Genet, Transgenom, Inc, Canadian PKU & Allied Disorders Inc, Natl PKU Alliance, Natl Urea Cycle Disorders Fdn, Propion Acidemia Fdn, United Mitochondrial Dis Fdn
C1 [Estrada-Veras, Juvianee; Gahl, William; Gochuico, Bernadette] NHGRI, Med Genet Branch, Off Clin Director, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1096-7192
J9 MOL GENET METAB
JI Mol. Genet. Metab.
PD MAR
PY 2012
VL 105
IS 3
BP 317
EP 317
PG 1
WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research &
Experimental
SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental
Medicine
GA 913VV
UT WOS:000301906400066
ER
PT J
AU McGuire, PJ
Gramignoli, R
Tarasenko, T
Wang, T
Levy, E
Diaz, GA
Strom, SC
AF McGuire, Peter J.
Gramignoli, Roberto
Tarasenko, Tatiana
Wang, Tony
Levy, Ezra
Diaz, George A.
Strom, Stephen C.
TI Cytokine depression of urea cycle function: A focus on ornithine
transcarbamylase
SO MOLECULAR GENETICS AND METABOLISM
LA English
DT Meeting Abstract
CT 35th Annual Meeting of the Society-for-Inherited-Metabolic-Disorders
(SIMD)
CY MAR 31-APR 03, 2012
CL Charlotte, NC
SP Soc Inherited Metabol Disorders (SIMD), Abbott Nutr (Abbott Metabol), Pfizer Inc, Shire, Actel Pharmaceut (ACTELION), Cytonet LLC, GeneDx, Genzyme, Hyper Therapeut, Inc, Mead Johnson Nutr, Orphan Europe Recordati Grp, Rare Dis Therapeut, Inc, Ucyclyd Pharma, Vitaflo, Appl Nutr Corp, ARUP Labs, BioMarin Pharmaceut, Inc, Cambrooke Foods, Inc, Emory Genet Lab, Hitachi High Technol Amer, Inc, Prevent Genet, Transgenom, Inc, Canadian PKU & Allied Disorders Inc, Natl PKU Alliance, Natl Urea Cycle Disorders Fdn, Propion Acidemia Fdn, United Mitochondrial Dis Fdn
C1 [McGuire, Peter J.; Tarasenko, Tatiana] NHGRI, NIH, Bethesda, MD 20892 USA.
[Gramignoli, Roberto; Strom, Stephen C.] Univ Pittsburgh, Dept Pathol, Pittsburgh, PA 15260 USA.
[Wang, Tony; Levy, Ezra; Diaz, George A.] Mt Sinai Sch Med, Dept Genet & Genom Sci, New York, NY USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1096-7192
J9 MOL GENET METAB
JI Mol. Genet. Metab.
PD MAR
PY 2012
VL 105
IS 3
BP 338
EP 339
PG 2
WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research &
Experimental
SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental
Medicine
GA 913VV
UT WOS:000301906400107
ER
PT J
AU Pearl, PL
Theodore, WH
McCarter, R
McGavin, C
Sweetman, L
Gibson, KM
AF Pearl, P. L.
Theodore, W. H.
McCarter, R.
McGavin, C.
Sweetman, L.
Gibson, K. M.
TI Taurine intervention in succinic semialdehyde dehydrogenase (SSADH)
deficiency: An open label trial
SO MOLECULAR GENETICS AND METABOLISM
LA English
DT Meeting Abstract
CT 35th Annual Meeting of the Society-for-Inherited-Metabolic-Disorders
(SIMD)
CY MAR 31-APR 03, 2012
CL Charlotte, NC
SP Soc Inherited Metabol Disorders (SIMD), Abbott Nutr (Abbott Metabol), Pfizer Inc, Shire, Actel Pharmaceut (ACTELION), Cytonet LLC, GeneDx, Genzyme, Hyper Therapeut, Inc, Mead Johnson Nutr, Orphan Europe Recordati Grp, Rare Dis Therapeut, Inc, Ucyclyd Pharma, Vitaflo, Appl Nutr Corp, ARUP Labs, BioMarin Pharmaceut, Inc, Cambrooke Foods, Inc, Emory Genet Lab, Hitachi High Technol Amer, Inc, Prevent Genet, Transgenom, Inc, Canadian PKU & Allied Disorders Inc, Natl PKU Alliance, Natl Urea Cycle Disorders Fdn, Propion Acidemia Fdn, United Mitochondrial Dis Fdn
C1 [Pearl, P. L.; McCarter, R.; McGavin, C.] George Washington Univ, Childrens Natl Med Ctr, Sch Med, Washington, DC USA.
[Theodore, W. H.] NINDS, Clin Epilepsy Sect, NIH, Bethesda, MD 20892 USA.
[Sweetman, L.] Baylor Univ, Med Ctr, Inst Metab Dis, Dallas, TX USA.
[Gibson, K. M.] Michigan Technol Univ, Houghton, MI 49931 USA.
NR 0
TC 2
Z9 2
U1 0
U2 0
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1096-7192
J9 MOL GENET METAB
JI Mol. Genet. Metab.
PD MAR
PY 2012
VL 105
IS 3
BP 346
EP 346
PG 1
WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research &
Experimental
SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental
Medicine
GA 913VV
UT WOS:000301906400118
ER
PT J
AU Markello, TC
Han, T
Carlson-Donohoe, H
Ahaghotu, C
Harper, U
Jones, M
Chandrasekharappa, S
Anikster, Y
Adams, DR
Gahl, WA
Boerkoel, CF
AF Markello, Thomas C.
Han, Ted
Carlson-Donohoe, Hannah
Ahaghotu, Chidi
Harper, Ursula
Jones, MaryPat
Chandrasekharappa, Settara
Anikster, Yair
Adams, David R.
Gahl, William A.
Boerkoel, Cornelius F.
CA NISC Comparative Sequencing Progra
TI Recombination mapping using Boolean logic and high-density SNP
genotyping for exome sequence filtering
SO MOLECULAR GENETICS AND METABOLISM
LA English
DT Article
DE Linkage; Recombination; Mapping; Exome sequencing; Single nucleotide
variants
ID LINKAGE ANALYSIS; PEDIGREE ANALYSIS; HUMAN GENOME; IDENTIFICATION; GENE;
MAP
AB Whole genome sequence data for small pedigrees has been shown to provide sufficient information to resolve detailed haplotypes in small pedigrees. Using such information, recombinations can be mapped onto chromosomes, compared with the segregation of a disease of interest and used to filter genome sequence variants. We now show that relatively inexpensive SNP array data from small pedigrees can be used in a similar manner to provide a means of identifying regions of interest in exome sequencing projects. We demonstrate that in those situations where one can assume complete penetrance and parental DNA is available, SNP recombination mapping using Boolean logic identifies chromosomal regions identical to those detected by multipoint linkage using microsatellites but with much less computation. We further show that this approach is successful because the probability of a double crossover between informative SNP loci is negligible. Our observations provide a rationale for using SNP arrays and recombination mapping as a rapid and cost-effective means of incorporating chromosome segregation information into exome sequencing projects intended for disease-gene identification. Published by Elsevier Inc.
C1 [Markello, Thomas C.; Han, Ted; Ahaghotu, Chidi; Anikster, Yair; Adams, David R.; Gahl, William A.] NHGRI, NIH, Bethesda, MD 20892 USA.
[Markello, Thomas C.; Adams, David R.; Gahl, William A.; Boerkoel, Cornelius F.] NIH, NIH Undiag Dis Program, Off Director, Bethesda, MD 20892 USA.
[Carlson-Donohoe, Hannah] Univ Minnesota, Sch Med, Minneapolis, MN 55455 USA.
[Harper, Ursula; Jones, MaryPat; Chandrasekharappa, Settara] NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA.
[Anikster, Yair] Tel Aviv Univ, Edmond & Lily Safra Childrens Hosp, Sheba Med Ctr, IL-69978 Tel Aviv, Israel.
[Anikster, Yair] Tel Aviv Univ, Sackler Sch Med, IL-69978 Tel Aviv, Israel.
[NISC Comparative Sequencing Progra] Natl Intramural Sequencing Ctr, Rockville, MD 20852 USA.
RP Markello, TC (reprint author), NHGRI, NIH, Bldg 10-10C107,10 Ctr Dr, Bethesda, MD 20892 USA.
EM markellot@mail.nih.gov
FU NIH(Office of Rare Disease Research, Office of the Director, NIH; NHGRI;
and NIH Clinical Center); NHGRI
FX The authors appreciate the advice and assistance of the Genomics Core of
the NHGRI. This work was supported by the NIH Undiagnosed Diseases
Program (Office of Rare Disease Research, Office of the Director, NIH;
NHGRI; and NIH Clinical Center) and by the Intramural Research Program
of the NHGRI.
NR 26
TC 7
Z9 7
U1 0
U2 2
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1096-7192
J9 MOL GENET METAB
JI Mol. Genet. Metab.
PD MAR
PY 2012
VL 105
IS 3
BP 382
EP 389
DI 10.1016/j.ymgme.2011.12.014
PG 8
WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research &
Experimental
SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental
Medicine
GA 913VV
UT WOS:000301906400160
PM 22264778
ER
PT J
AU Rao, M
AF Rao, Mahendra
TI The NIH and the regenerative medicine field
SO REGENERATIVE MEDICINE
LA English
DT Editorial Material
DE adult stem cell; embryonic stem cell; ESC; induced pluripotent stem
cell; mesenchymal stem cell; MSC; personalized therapy; regenerative
medicine; regulatory standards; stem cell; translational
ID CELL-BASED THERAPY
C1 NIH, Ctr Regenerat Med, Bethesda, MD 20892 USA.
RP Rao, M (reprint author), NIH, Ctr Regenerat Med, 50 Ctr Dr,Room 1140, Bethesda, MD 20892 USA.
EM mahendra.rao@nih.gov
NR 5
TC 2
Z9 2
U1 0
U2 0
PU FUTURE MEDICINE LTD
PI LONDON
PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3
1QB, ENGLAND
SN 1746-0751
J9 REGEN MED
JI Regen. Med.
PD MAR
PY 2012
VL 7
IS 2
BP 129
EP 131
DI 10.2217/RME.12.8
PG 3
WC Cell & Tissue Engineering; Engineering, Biomedical
SC Cell Biology; Engineering
GA 906EH
UT WOS:000301327200001
PM 22397601
ER
PT J
AU Sizemore, CF
Fauci, AS
AF Sizemore, Christine F.
Fauci, Anthony S.
TI Transforming Biomedical Research to Develop Effective TB Vaccines: The
Next Ten Years
SO TUBERCULOSIS
LA English
DT Editorial Material
C1 [Sizemore, Christine F.] NIAID, TB Leprosy & Other Mycobacterial Dis Sect, Div Microbiol & Infect Dis, NIH, Bethesda, MD 20892 USA.
RP Sizemore, CF (reprint author), NIAID, TB Leprosy & Other Mycobacterial Dis Sect, Div Microbiol & Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
NR 0
TC 1
Z9 2
U1 0
U2 0
PU CHURCHILL LIVINGSTONE
PI EDINBURGH
PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE,
LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND
SN 1472-9792
J9 TUBERCULOSIS
JI Tuberculosis
PD MAR
PY 2012
VL 92
SU 1
BP S2
EP S3
PG 2
WC Immunology; Microbiology; Respiratory System
SC Immunology; Microbiology; Respiratory System
GA 914LM
UT WOS:000301951500002
PM 22441154
ER
PT J
AU Das, S
Singh, S
Chigurupati, S
Mughal, MR
Kumar, A
Patra, CR
Oommen, S
Vlahakis, NE
Mukhopadhyay, D
Self, WT
Mattson, MP
Seal, S
AF Das, S.
Singh, S.
Chigurupati, S.
Mughal, M. R.
Kumar, A.
Patra, C. R.
Oommen, S.
Vlahakis, N. E.
Mukhopadhyay, D.
Self, W. T.
Mattson, M. P.
Seal, S.
TI CERIUM OXIDE NANOPARTICLES CAN INDUCE PRO-ANGIOGENESIS AND FACILITATE
WOUND HEALING
SO WOUND REPAIR AND REGENERATION
LA English
DT Meeting Abstract
C1 [Das, S.; Kumar, A.; Seal, S.] Adv Mat Proc Anal Ctr, Orlando, FL USA.
[Chigurupati, S.; Mughal, M. R.; Mattson, M. P.] NIA, Lab Neurosci, Intramural Res Program, Baltimore, MD 21224 USA.
[Singh, S.; Self, W. T.] Burnett Sch Biomed Sci, Dept Mol Biol & Microbiol, Orlando, FL USA.
[Patra, C. R.; Mukhopadhyay, D.] Mayo Clin, Coll Med, Dept Biochem & Mol Biol, Rochester, MN USA.
[Oommen, S.] Mayo Clin, Div Pulm & Crit Care, Rochester, MN USA.
[Vlahakis, N. E.] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA.
RI Self, William/A-6704-2008; Mattson, Mark/F-6038-2012; Kumar,
Amit/E-9483-2011
NR 0
TC 2
Z9 2
U1 0
U2 1
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1067-1927
J9 WOUND REPAIR REGEN
JI Wound Repair Regen.
PD MAR-APR
PY 2012
VL 20
IS 2
BP A20
EP A20
PG 1
WC Cell Biology; Dermatology; Medicine, Research & Experimental; Surgery
SC Cell Biology; Dermatology; Research & Experimental Medicine; Surgery
GA 901DY
UT WOS:000300943100034
ER
PT J
AU Anixt, JS
Copeland-Linder, N
Haynie, D
Cheng, TL
AF Anixt, Julia S.
Copeland-Linder, Nikeea
Haynie, Denise
Cheng, Tina L.
TI Burden of Unmet Mental Health Needs in Assault-Injured Youths Presenting
to the Emergency Department
SO ACADEMIC PEDIATRICS
LA English
DT Article
DE aggression; assault; emergency department; gender; mental health
ID INTERPERSONAL VIOLENCE; PSYCHOSOCIAL NEEDS; ADOLESCENTS; EXPOSURE;
INTERVENTION; BEHAVIORS; CHILDREN; TRAUMA; RISK
AB OBJECTIVES: To determine if there is a gap between behavioral symptoms and previously recognized mental health conditions in youth victims of peer assault injuries and to describe gender differences in psychological symptoms.
METHODS: A cross-sectional comparison of rates of previously diagnosed mental health conditions and clinical range behavioral symptoms as measured by the Child Behavior Checklist (CBCL) in 168 youths (range, 10-15 years old) presenting to the emergency department (ED) after an interpersonal assault injury. The Fisher exact test was used for comparisons.
RESULTS: Mental health symptoms were common among assault-injured youths. More than half of the youths demonstrating clinical range symptoms on the attention problems or anxious/depressed scales of the CBCL had no prior diagnosis of these conditions. Girls were more likely than boys to exhibit clinical range aggressive behavior symptoms (odds ratio [OR], 3.61; 95% confidence interval [CI], 1.64-7.97). Aggressive behavior was associated with clinical range scores on the other problem scales of the CBCL.
CONCLUSIONS: After an ED visit for an assault-related injury, less than half of 10 to 15 year olds with significant symptoms of common mental conditions reported having a previously diagnosed disorder, reflecting a burden of unmet psychological needs. An ED visit for an assault injury provides an opportunity to screen for emotional/behavioral symptoms and to refer to appropriate follow-up mental health care.
C1 [Anixt, Julia S.] Univ Cincinnati, Cincinnati Childrens Hosp, Med Ctr, Div Dev & Behav Pediat, Cincinnati, OH 45229 USA.
[Copeland-Linder, Nikeea; Cheng, Tina L.] Johns Hopkins Univ, Sch Med, Div Gen Pediat & Adolescent Med, Baltimore, MD USA.
[Haynie, Denise] Natl Inst Child Hlth & Human Dev, Bethesda, MD USA.
RP Anixt, JS (reprint author), Univ Cincinnati, Cincinnati Childrens Hosp, Med Ctr, Div Dev & Behav Pediat, 3333 Bumet Ave,MLC 4002, Cincinnati, OH 45229 USA.
EM julia.anixt@cchmc.org
OI Haynie, Denise/0000-0002-8270-6079
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development; Maternal and Child Health Bureau, Health Resources and
Services Administration, Department of Health and Human Services
[R40MC00174]; DC-Baltimore Research Center on Child Health Disparities
from the National Center on Minority Health and Health Disparities [P20
MD00165]; Robert Wood Johnson Clinical Scholars Program
FX This project was supported by intramural and extramural research
programs of the Eunice Kennedy Shriver National Institute of Child
Health and Human Development, (D.L.H. and T.L.C.), the Maternal and
Child Health Bureau (Title V Social Security Act), Health Resources and
Services Administration, Department of Health and Human Services,
R40MC00174. This publication was supported by the DC-Baltimore Research
Center on Child Health Disparities Grant P20 MD00165 from the National
Center on Minority Health and Health Disparities. Its contents are
solely the responsibility of the authors and do not necessarily
represent the official views of the funding agency. Support for this
analysis was provided by the Robert Wood Johnson Clinical Scholars
Program. The authors would like to thank Alan Simon and David Schonfeld
for their help with this project.
NR 19
TC 4
Z9 4
U1 2
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1876-2859
J9 ACAD PEDIATR
JI Acad. Pediatr.
PD MAR-APR
PY 2012
VL 12
IS 2
BP 125
EP 130
PG 6
WC Pediatrics
SC Pediatrics
GA 910HE
UT WOS:000301627000009
PM 22112395
ER
PT J
AU Cole, NB
Donaldson, JG
AF Cole, Nelson B.
Donaldson, Julie G.
TI Releasable SNAP-tag Probes for Studying Endocytosis and Recycling
SO ACS CHEMICAL BIOLOGY
LA English
DT Article
ID PROTEIN-COUPLED RECEPTORS; MEDIATED ENDOCYTOSIS; IN-VIVO; TRAFFICKING;
ARRESTIN; RESENSITIZATION; ENDOSOMES; LYSOSOMES; GPCRS; FRET
AB Site-specific labeling of cellular proteins with chemicals probes is a powerful tool for live cell imaging of biological processes. One popular system, known as the SNAP tag is based on an engineered variant of the 20-kDa DNA-repair protein O(6-)alkylguanine-DNA-alkyltransferase (AGT) that covalent reacts with O-6 benzylguanine (BG) and can be derivated with a number of reporter groups For studying the endocytosis and recycling of cell surface proteins, the covalent nature of BG binding to the SNAP tag is problematic, since removing excess noninternalized probe from the cell surface is not feasible. Here we describe a modification of the SNAP tag technology that permits the rapid release of fluorescently labeled probes from the cell surface without affective of fluorescently labeled probes from the cell surface without affecting the population of labelled molecules sequested within endosomes. This simple yet effective approach allows quantitative measurements of endocytosis and recycling in both imaging and biochemical assay and is especially useful when studying endosomal dynamics in live cells.
C1 [Cole, Nelson B.; Donaldson, Julie G.] NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Donaldson, JG (reprint author), NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA.
EM jdonalds@helix.nih.gov
FU National Heart, Lung, and Blood Institute at NIH
FX We thank G. Griffiths and A. Dulcey at the Imaging Probe Development
Center, NHLBI/NIH for help during the initial phases of this work and
thank C. Combs of the Light Microscopy Core Facility/NHLBI for help with
image quantitation. We acknowledge the Biochemistry Core Facility
(NHLBI) and especially D.-Y. Lee and R Levine for help with compound
synthesis and mass spectrometry analysis. We also thank C. Waterman and
L. Greene (both NHLBI) and G. Patterson (NIBIB) for comments on the
manuscript. The Intramural Research Program in the National Heart, Lung,
and Blood Institute at the NIH supported this work.
NR 24
TC 14
Z9 15
U1 1
U2 19
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1554-8929
J9 ACS CHEM BIOL
JI ACS Chem. Biol.
PD MAR
PY 2012
VL 7
IS 3
BP 464
EP 469
DI 10.1021/cb2004252
PG 6
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 908TQ
UT WOS:000301515800003
PM 22216966
ER
PT J
AU Brown, D
Pipe, ME
Lewis, C
Lamb, ME
Orbach, Y
AF Brown, Deirdre
Pipe, Margaret-Ellen
Lewis, Charlie
Lamb, Michael E.
Orbach, Yael
TI How Do Body Diagrams Affect the Accuracy and Consistency of Children's
Reports of Bodily Touch Across Repeated Interviews?
SO APPLIED COGNITIVE PSYCHOLOGY
LA English
DT Article
ID SEXUAL-ABUSE; QUESTIONS; MEMORIES; REMEMBER; EVENTS
AB We examined the amount, accuracy, and consistency of information reported by 58 5- to 7-year-old children about a staged event that included physical contact/touching. Both 1 and 7months following the event, children were asked both open and yes/no questions about touch [i] when provided with human body diagrams (HBDs), [ii] following instruction and practice using the HBDs, or [iii] without HBDs. Children interviewed with HBDs reported more information at 7months, but a high proportion of inaccurate touches. Children seldom repeated touch-related information across the two interviews and did not incorporate errors made in the 1-month interview into their open-ended accounts 6months later. Asking children to talk about innocuous touch may lead them to report unreliable information, especially when HBDs are used as aids and repeated interviews are conducted across delays that resemble those typical of forensic contexts. Copyright (C) 2011 John Wiley & Sons, Ltd.
C1 [Lamb, Michael E.] Univ Cambridge, Cambridge CB2 3RQ, England.
[Brown, Deirdre] Univ Victoria, Wellington, New Zealand.
[Pipe, Margaret-Ellen] CUNY Brooklyn Coll, New York, NY USA.
[Lewis, Charlie] Univ Lancaster, Lancaster, England.
[Orbach, Yael] NICHHD, Bethesda, MD 20892 USA.
RP Lamb, ME (reprint author), Univ Cambridge, Free Sch Lane, Cambridge CB2 3RQ, England.
EM mel37@cam.ac.uk
NR 29
TC 3
Z9 3
U1 0
U2 1
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0888-4080
J9 APPL COGNITIVE PSYCH
JI Appl. Cogn. Psychol.
PD MAR-APR
PY 2012
VL 26
IS 2
BP 174
EP 181
DI 10.1002/acp.1828
PG 8
WC Psychology, Experimental
SC Psychology
GA 901MM
UT WOS:000300971000002
ER
PT J
AU Willis, JR
Jefferys, JL
Vitale, S
Ramulu, PY
AF Willis, Jeffrey R.
Jefferys, Joan L.
Vitale, Susan
Ramulu, Pradeep Y.
TI Visual Impairment, Uncorrected Refractive Error, and
Accelerometer-Defined Physical Activity in the United States
SO ARCHIVES OF OPHTHALMOLOGY
LA English
DT Article
ID QUALITY-OF-LIFE; OLDER-ADULTS; MACULAR DEGENERATION; POSTURAL STABILITY;
RISK-FACTORS; VISION LOSS; MORTALITY; MOBILITY; BALANCE; DISEASE
AB Objective: To examine how accelerometer-measured physical activity is affected by visual impairment (VI) and uncorrected refractive error (URE).
Design: Cross-sectional study using data from the 2003-2004/2005-2006 National Health and Nutritional Examination Survey. Visual impairment was defined as better-eye postrefraction visual acuity worse than 20/40. Uncorrected refractive error was defined as better-eye presenting visual acuity of 20/50 or worse, improving to 20/40 or better with refraction. Adults older than 20 years with normal sight, URE, and VI were analyzed. The main outcome measures were steps per day and daily minutes of moderate or vigorous physical activity (MVPA).
Results: Five thousand seven hundred twenty-two participants (57.1%) had complete visual acuity and accelerometer data. Individuals with normal sight took an average of 9964 steps per day and engaged in an average of 23.5 minutes per day of MVPA, as compared with 9742 steps per day and 23.1 minutes per day of MVPA in individuals with URE (P>.50 for both) and 5992 steps per day and 9.3 minutes/d of MVPA in individuals with VI (P<.01 for both). In multivariable models, individuals with VI took 26% fewer steps per day (P<.01; 95% CI, 18%-34%) and spent 48% less time in MVPA (P<.01; 95% CI, 37%-57%) than individuals with normal sight. The decrement in steps and MVPA associated with VI equaled or exceeded that associated with self-reported chronic obstructive pulmonary disease, diabetes mellitus, arthritis, stroke, or congestive heart failure.
Conclusions: Visual impairment, but not URE, impacts physical activity equal to or greater than other serious medical conditions. The substantial decrement in physical activity observed in nonrefractive vision loss highlights a need for better strategies to safely improve mobility and increase physical activity in this group.
C1 [Willis, Jeffrey R.; Jefferys, Joan L.; Vitale, Susan; Ramulu, Pradeep Y.] Johns Hopkins Sch Med, Wilmer Eye Inst, Baltimore, MD USA.
[Vitale, Susan] NEI, Div Epidemiol & Clin Applicat, NIH, Bethesda, MD 20892 USA.
RP Ramulu, PY (reprint author), Johns Hopkins Univ Hosp, 600 N Wolfe St,Maumenee B110, Baltimore, MD 21287 USA.
EM pramulu1@jhmi.edu
FU National Center for Health Statistics, Centers for Disease Control and
Prevention; National Eye Institute, National Institutes of Health
[Z01EY000402]; National Cancer Institute; National Eye Institute
[EY018595]; Research to Prevent Blindness
FX NHANES is sponsored by the National Center for Health Statistics,
Centers for Disease Control and Prevention. Additional funding for the
NHANES Vision Component was provided by the National Eye Institute,
National Institutes of Health (Intramural Re-search Program grant
Z01EY000402) and funding for the accelerometry data was provided by the
National Cancer Institute. The work was also sponsored by National Eye
Institute grant EY018595 and a Research to Prevent Blindness Robert &
Helen Schaub Special Scholar Award.
NR 54
TC 25
Z9 25
U1 0
U2 5
PU AMER MEDICAL ASSOC
PI CHICAGO
PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA
SN 0003-9950
J9 ARCH OPHTHALMOL-CHIC
JI Arch. Ophthalmol.
PD MAR
PY 2012
VL 130
IS 3
BP 329
EP 335
PG 7
WC Ophthalmology
SC Ophthalmology
GA 906NW
UT WOS:000301353400008
PM 22411662
ER
PT J
AU Urusova, DV
Isupov, MN
Antonyuk, S
Kachalova, GS
Obmolova, G
Vagin, AA
Lebedev, AA
Burenkov, GP
Dauter, Z
Bartunik, HD
Lamzin, VS
Melik-Adamyan, WR
Mueller, TD
Schnackerz, KD
AF Urusova, Darya V.
Isupov, Michail N.
Antonyuk, Svetlana
Kachalova, Galina S.
Obmolova, Galina
Vagin, Alexei A.
Lebedev, Andrey A.
Burenkov, Gleb P.
Dauter, Zbigniew
Bartunik, Hans D.
Lamzin, Victor S.
Melik-Adamyan, William R.
Mueller, Thomas D.
Schnackerz, Klaus D.
TI Crystal structure of D-serine dehydratase from Escherichia coli
SO BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS
LA English
DT Article
DE D-Serine dehydratase; Pyridoxal 5 '-phosphate; Type II fold; Open and
closed conformation; alpha,beta elimination
ID O-ACETYLSERINE SULFHYDRYLASE; PHOSPHATE BINDING-SITE; D-AMINO ACIDS;
PYRIDOXAL 5'-PHOSPHATE; SALMONELLA-TYPHIMURIUM; ACTIVE-SITE;
3-DIMENSIONAL STRUCTURE; CONFORMATIONAL-CHANGE; ALANINE RACEMASE;
PROTEIN MODELS
AB D-Serine dehydratase from Escherichia coli is a member of the beta-family (fold-type II) of the pyridoxal 5'-phosphate-dependent enzymes, catalyzing the conversion of D-serine to pyruvate and ammonia. The crystal structure of monomeric D-serine dehydratase has been solved to 1.97 angstrom-resolution for an orthorhombic data set by molecular replacement. In addition, the structure was refined in a monoclinic data set to 1.55 angstrom resolution. The structure of DSD reveals a larger pyridoxal 5'-phosphate-binding domain and a smaller domain. The active site of DSD is very similar to those of the other members of the beta-family. Lys118 forms the Schiff base to PLP, the cofactor phosphate group is liganded to a tetraglycine cluster Gly279-Gly283, and the 3-hydroxyl group of PLP is liganded to Asn170 and N1 to Thr424, respectively. In the closed conformation the movement of the small domain blocks the entrance to active site of DSD. The domain movement plays an important role in the formation of the substrate recognition site and the catalysis of the enzyme. Modeling of D-serine into the active site of DSD suggests that the hydroxyl group of D-serine is coordinated to the carboxyl group of Asp238. The carboxyl oxygen of D-serine is coordinated to the hydroxyl group of Ser167 and the amide group of Leu171 (O1), whereas the O2 of the carboxyl group of D-serine is hydrogen-bonded to the hydroxyl group of Ser167 and the amide group of Thr168. A catalytic mechanism very similar to that proposed for L-serine dehydratase is discussed. (c) 2011 Elsevier B.V. All rights reserved.
C1 [Schnackerz, Klaus D.] Univ Wurzburg, Theodor Boveri Inst Biowissensch, D-97074 Wurzburg, Germany.
[Urusova, Darya V.; Melik-Adamyan, William R.] Russian Acad Sci, Inst Crystallog, Moscow 119333, Russia.
[Isupov, Michail N.] Univ Exeter, Biosci Coll Life & Environm Sci, Exeter EX4 4QD, Devon, England.
[Antonyuk, Svetlana] Univ Liverpool, Fac Hlth & Life Sci, Inst Integrat Biol, Mol Biophys Grp, Liverpool L69 7ZB, Merseyside, England.
[Obmolova, Galina] Centocor R&D, Radnor, PA 19087 USA.
[Kachalova, Galina S.; Bartunik, Hans D.] Max Planck Unit Struct Mol Biol, MPG ASMB DESY, D-22603 Hamburg, Germany.
[Vagin, Alexei A.; Lebedev, Andrey A.] Univ York, Dept Chem, Struct Biol Lab, York YO10 5YW, N Yorkshire, England.
[Burenkov, Gleb P.; Lamzin, Victor S.] DESY, European Mol Biol Lab, Hamburg Unit, D-22607 Hamburg, Germany.
[Dauter, Zbigniew] Argonne Natl Lab, Synchrotron Radiat Res Sect, NCI, MCL,Biosci Div, Argonne, IL 60439 USA.
[Mueller, Thomas D.] Univ Wurzburg, Julius von Sachs Inst, Lehrstuhl Pflanzenphysiol & Biophys, D-97082 Wurzburg, Germany.
RP Schnackerz, KD (reprint author), Univ Wurzburg, Theodor Boveri Inst Biowissensch, D-97074 Wurzburg, Germany.
EM schnacke@biozentrum.uni-wuerzburg.de
OI Antonyuk, Svetlana/0000-0002-2779-9946; Lamzin,
Victor/0000-0002-6058-7793; Bourenkov, Gleb/0000-0002-2617-5920; Isupov,
Michail/0000-0001-6842-4289
NR 53
TC 6
Z9 7
U1 0
U2 11
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1570-9639
J9 BBA-PROTEINS PROTEOM
JI BBA-Proteins Proteomics
PD MAR
PY 2012
VL 1824
IS 3
BP 422
EP 432
DI 10.1016/j.bbapap.2011.10.017
PG 11
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 909JV
UT WOS:000301561700003
PM 22197591
ER
PT J
AU Zarate, C
Furey, M
AF Zarate, C.
Furey, M.
TI A translational perspective in the search for improved treatments for
bipolar disorder
SO BIPOLAR DISORDERS
LA English
DT Meeting Abstract
CT 5th Biennial Conference of the
International-Society-for-Bipolar-Disorders
CY MAR 14-17, 2012
CL Istanbul, TURKEY
SP Int Soc Bipolar Disorders
DE biomarkers; bipolar; cholinergic; glutamate; novel treatments
C1 [Zarate, C.; Furey, M.] NIMH, Expt Therapeut & Pathophysiol Branch & Sect Neuro, Div Intramural Res, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1398-5647
J9 BIPOLAR DISORD
JI Bipolar Disord.
PD MAR
PY 2012
VL 14
SU 1
SI SI
BP 15
EP 15
PG 1
WC Clinical Neurology; Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 908ZG
UT WOS:000301531000010
ER
PT J
AU Selvaraj, S
Arnone, D
Job, D
Stanfield, A
Farrow, TFD
Nugent, AC
Scherk, H
Gruber, O
Chen, XH
Sachdev, PS
Dickstein, DP
Malhi, GS
Ha, TH
Ha, K
Phillips, ML
McIntosh, AM
AF Selvaraj, Sudhakar
Arnone, Danilo
Job, Dominic
Stanfield, Andrew
Farrow, Tom F. D.
Nugent, Allison C.
Scherk, Harald
Gruber, Oliver
Chen, Xiaohua
Sachdev, Perminder S.
Dickstein, Daniel P.
Malhi, Gin S.
Ha, Tae H.
Ha, Kyooseob
Phillips, Mary L.
McIntosh, Andrew M.
TI Grey matter differences in bipolar disorder: a meta-analysis of
voxel-based morphometry studies
SO BIPOLAR DISORDERS
LA English
DT Review
DE bipolar disorder; grey matter; magnetic resonance imaging;
meta-analysis; voxel-based morphometry
ID ORBITOFRONTAL CORTEX; FACIAL EXPRESSIONS; VOLUME DIFFERENCES; MAJOR
DEPRESSION; CORPUS-CALLOSUM; MOOD DISORDERS; I DISORDER; SCHIZOPHRENIA;
ACTIVATION; ABNORMALITIES
AB Objective: Several neuroimaging studies have reported structural brain differences in bipolar disorder using automated methods. While these studies have several advantages over those using region of interest techniques, no study has yet estimated a summary effect size or tested for between-study heterogeneity. We sought to address this issue using metaanalytic techniques applied for the first time in bipolar disorder at the level of the individual voxel.
Methods: A systematic review identified 16 voxel-based morphometry (VBM) studies comparing individuals with bipolar disorder with unaffected controls, of which eight were included in the meta-analysis. In order to take account of heterogeneity, summary effect sizes were computed using a random-effects model with appropriate correction for multiple testing.
Results: Compared with controls, subjects with bipolar disorder had reduced grey matter in a single cluster encompassing the right ventral prefrontal cortex, insula, temporal cortex, and claustrum. Study heterogeneity was widespread throughout the brain; though the significant cluster of grey matter reduction remained once these extraneous voxels had been removed. We found no evidence of publication bias (Eggers p = 0.63).
Conclusions: Bipolar disorder is consistently associated with reductions in right prefrontal and temporal lobe grey matter. Reductions elsewhere may be obscured by clinical and methodological heterogeneity.
C1 [Selvaraj, Sudhakar] Kings Coll London, Inst Psychiat, Dept Psychosis Studies, London SE5 7AF, England.
[Arnone, Danilo] Inst Psychiat, Dept Psychol Med, Affect Disorder Res Grp, London SE5 8AF, England.
[Job, Dominic; Stanfield, Andrew; McIntosh, Andrew M.] Univ Edinburgh, Royal Edinburgh Hosp, Div Psychiat, Edinburgh, Midlothian, Scotland.
[Farrow, Tom F. D.] Univ Sheffield, Sheffield, S Yorkshire, England.
[Nugent, Allison C.] NIMH, Sect Neuroimaging, Mood Anxiety Disorders Program, Bethesda, MD 20892 USA.
[Scherk, Harald; Gruber, Oliver] Univ Gottingen, Dept Psychiat & Psychotherapy, Gottingen, Germany.
[Chen, Xiaohua; Sachdev, Perminder S.] Univ New S Wales, Sch Psychiat, Sydney, NSW, Australia.
[Dickstein, Daniel P.] Brown Univ, Bradley Hasbro Childrens Res Ctr, Providence, RI 02912 USA.
[Malhi, Gin S.] Univ Sydney, Dept Psychiat, CADE Clin, Sydney, NSW 2006, Australia.
[Malhi, Gin S.] Univ Sydney, Discipline Psychol Med, Sydney, NSW 2006, Australia.
[Ha, Tae H.; Ha, Kyooseob] Seoul Natl Univ, Bundang Hosp, Dept Psychiat, Seoul, South Korea.
[Phillips, Mary L.] Univ Pittsburgh, Sch Med, Western Psychiat Inst & Clin, Dept Psychiat, Pittsburgh, PA USA.
RP Selvaraj, S (reprint author), Kings Coll London, Inst Psychiat, Dept Psychosis Studies, 16 De Crespigny Pk, London SE5 7AF, England.
EM sudhakar.selvaraj@kcl.ac.uk
RI Arnone, Danilo/A-3974-2012; Ha, Kyooseob/J-5698-2012; McIntosh,
Andrew/B-9379-2008; selvaraj, sudhakar/J-4295-2014; Dickstein,
Daniel/L-3210-2016; Farrow, Tom/B-5003-2009
OI Nugent, Allison/0000-0003-2569-2480; Sachdev,
Perminder/0000-0002-9595-3220; McIntosh, Andrew/0000-0002-0198-4588;
selvaraj, sudhakar/0000-0002-9494-172X; Dickstein,
Daniel/0000-0003-1647-5329; Stanfield, Andrew/0000-0003-2459-1434;
Arnone, Danilo/0000-0003-3831-2301; Job, Dominic/0000-0002-7829-7217;
Farrow, Tom/0000-0001-5096-6370
FU UK Medical Research Council; Health Foundation; NHMRC [510135]; NIMH
[K22MH074945]; American Foundation; AstraZeneca; Eli Lilly Co.;
Jansen-Cilag; Organon; Pfizer; Wyeth; Janssen; Otsuka; Servier;
GlaxoSmithKline; TMRI
FX DA is currently supported by the UK Medical Research Council, and AMM is
supported by the Health Foundation through a Clinician Scientist
Fellowship. GSM is supported by an NHMRC Program Grant 510135. DPD is
currently supported by an NIMH career development award (K22MH074945)
and an American Foundation for Suicide Prevention Young Investigator
Award.; TFDF has received honoraria for talks from Jansen-Cilag,
AstraZeneca, and Cambian Healthcare. GSM has, in the past three years,
served on a number of international and national pharmaceutical advisory
boards, received funding for research, and received honoraria for talks
at sponsored meetings worldwide involving AstraZeneca, Eli Lilly & Co.,
Jansen-Cilag, Organon, Pfizer, and Wyeth. KH has received grants and/or
honoraria from Pfizer, Eli Lilly & Co., Janssen, Otsuka, Servier,
AstraZeneca, and GlaxoSmithKline. AMM has received funding from TMRI, a
collaboration between the Scottish Universities and Wyeth
Pharmaceuticals. SS, DA, DJ, AS, ACN, HS, OG, XC, PSS, DPD, THH, and MLP
have no competing interests to report.
NR 65
TC 90
Z9 90
U1 1
U2 17
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1398-5647
J9 BIPOLAR DISORD
JI Bipolar Disord.
PD MAR
PY 2012
VL 14
IS 2
BP 135
EP 145
DI 10.1111/j.1399-5618.2012.01000.x
PG 11
WC Clinical Neurology; Neurosciences; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 908ZE
UT WOS:000301530800002
PM 22420589
ER
PT J
AU Fagundes, CP
Glaser, R
Alfano, CM
Bennett, JM
Povoski, SP
Lipari, AM
Agnese, DM
Yee, LD
Carson, WE
Farrar, WB
Malarkey, WB
Kiecolt-Glaser, JK
AF Fagundes, Christopher P.
Glaser, Ronald
Alfano, Catherine M.
Bennett, Jeanette M.
Povoski, Stephen P.
Lipari, Adele M.
Agnese, Doreen M.
Yee, Lisa D.
Carson, William E., III
Farrar, William B.
Malarkey, William B.
Kiecolt-Glaser, Janice K.
TI Fatigue and herpesvirus latency in women newly diagnosed with breast
cancer
SO BRAIN BEHAVIOR AND IMMUNITY
LA English
DT Article
DE Cancer survivorship; Quality of life; Cytomegalovirus; Sickness
behaviors; Inflammation
ID EPSTEIN-BARR-VIRUS; QUALITY-OF-LIFE; CORONARY-ARTERY-DISEASE; INSOMNIA
SEVERITY INDEX; LONG-TERM; PERSISTENT FATIGUE; CYTOMEGALOVIRUS
REACTIVATION; INFLAMMATORY BIOMARKERS; DEPRESSIVE SYMPTOMS;
PROSTATE-CANCER
AB Fatigue is a notable clinical problem in cancer survivors, and understanding its pathophysiology is important. The current study sought to determine biomarkers of fatigue that exist before cancer treatment. Relationships between the expression of latent Epstein-Barr virus (EBV) and cytomegalovirus (CMV) and fatigue were examined in 158 women newly diagnosed with breast cancer or awaiting a positive diagnostic result. Higher CMV antibody titers, but not EBV antibody titers, were associated with a greater likelihood of being fatigued. Associations between fatigue and higher CMV antibody titers remained after controlling for alcohol use, smoking, comorbidities, depressive symptoms, age, BMI, cancer stage, and sleep problems. More sleep problems and higher levels of depressive symptoms were also associated with a greater likelihood of being fatigued. CMV antibody titers, but not EBV antibody titers, were associated with higher levels of C-reactive protein (CRP), but CRP was not associated with fatigue. When the cellular immune system is compromised, reactivation of latent herpesviruses may fuel chronic inflammatory responses. Prior work has suggested that fatigue may be related to inflammation and its associated sickness behaviors; accordingly, our findings may be tapping into this same physiological substrate. (C) 2011 Elsevier Inc. All rights reserved.
C1 [Fagundes, Christopher P.; Glaser, Ronald; Bennett, Jeanette M.; Malarkey, William B.; Kiecolt-Glaser, Janice K.] Ohio State Univ, Inst Behav Med Res, Coll Med, Columbus, OH 43210 USA.
[Glaser, Ronald; Carson, William E., III; Malarkey, William B.] Ohio State Univ, Coll Med, Dept Mol Virol Immunol & Med Genet, Columbus, OH 43210 USA.
[Glaser, Ronald; Malarkey, William B.] Ohio State Univ, Coll Med, Dept Internal Med, Columbus, OH 43210 USA.
[Glaser, Ronald; Povoski, Stephen P.; Agnese, Doreen M.; Yee, Lisa D.; Carson, William E., III; Farrar, William B.; Malarkey, William B.; Kiecolt-Glaser, Janice K.] Ohio State Univ, Coll Med, Ctr Comprehens Canc, Columbus, OH 43210 USA.
[Alfano, Catherine M.] NCI, Off Canc Survivorship, NIH, Bethesda, MD 20892 USA.
[Bennett, Jeanette M.] Ohio State Univ, Div Oral Biol, Coll Dent, Columbus, OH 43210 USA.
[Povoski, Stephen P.; Agnese, Doreen M.; Yee, Lisa D.; Carson, William E., III; Farrar, William B.] Ohio State Univ, Dept Surg, Coll Med, Columbus, OH 43210 USA.
[Lipari, Adele M.] Ohio State Univ, Dept Radiol, Coll Med, Columbus, OH 43210 USA.
[Malarkey, William B.; Kiecolt-Glaser, Janice K.] Ohio State Univ, Dept Psychiat, Coll Med, Columbus, OH 43210 USA.
RP Fagundes, CP (reprint author), Ohio State Univ, Inst Behav Med Res, Coll Med, 460 Med Ctr Dr, Columbus, OH 43210 USA.
EM christopher.fagundes@osumc.edu
RI Kiecolt-Glaser, Janice/A-3236-2009; Agnese, Doreen/I-1351-2012; Povoski,
Stephen/E-3887-2011; Carson, William/E-2846-2011; Glaser,
Ronald/E-3124-2011;
OI Kiecolt-Glaser, Janice/0000-0003-4900-9578; Bennett, Jeanette
M./0000-0002-8487-9774
FU NIH [CA131029, CA126857, DE014320, UL1RR025755, CA016058]; S. Robert
Davis endowment; Kathryn & Gilbert Mitchell endowment; American Cancer
Society [PF-11-007-01-CPPB]
FX Work on this project was supported in part by NIH Grants CA131029,
CA126857, DE014320, UL1RR025755, CA016058, the S. Robert Davis
endowment, the Kathryn & Gilbert Mitchell endowment, and an American
Cancer Society Postdoctoral Fellowship Grant PF-11-007-01-CPPB. We
appreciate the helpful assistance of Arenda Nolan and Cathie Atkinson.
We also thank Min Chen who performed the antibody assays.
NR 65
TC 15
Z9 15
U1 1
U2 7
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0889-1591
J9 BRAIN BEHAV IMMUN
JI Brain Behav. Immun.
PD MAR
PY 2012
VL 26
IS 3
BP 394
EP 400
DI 10.1016/j.bbi.2011.09.014
PG 7
WC Immunology; Neurosciences
SC Immunology; Neurosciences & Neurology
GA 906GD
UT WOS:000301332000005
PM 21988771
ER
PT J
AU Memarzadeh, F
Xu, WR
AF Memarzadeh, Farhad
Xu, Weiran
TI Role of air changes per hour (ACH) in possible transmission of airborne
infections
SO BUILDING SIMULATION
LA English
DT Article
DE infection transmission and control; risk assessment; air change rate
(ACH); computational fluid dynamics (CFD); patient room; ventilation
system design
ID INDOOR ENVIRONMENTS; ISOLATION ROOM; TRANSPORT CHARACTERISTICS;
EXPIRATORY DROPLETS; VENTILATION; AEROSOLS; FLOW; DISPERSION; REMOVAL;
SPREAD
AB The cost of nosocomial infections in the United States is estimated to be $4 billion to $5 billion annually. Applying a scientifically based analysis to disease transmission and performing a site specific risk analysis to determine the design of the ventilation system can provide real and long term cost savings. Using a scientific approach and convincing data, this paper hypothetically illustrates how a ventilation system design can be optimized to potentially reduce infection risk to occupants in an isolation room based on a thorough risk assessment without necessarily increasing ventilation airflow rate. A computational fluid dynamics (CFD) analysis was performed to examine the transport mechanism, particle path and a suggested control strategy for reducing airborne infectious disease agents. Most studies on the transmission of infectious disease particles have concentrated primarily on air changes per hour (ACH) and how ACH provides a dilution factor for possible infectious agents. Although increasing ventilation airflow rate does dilute concentrations better when the contaminant source is constant, it does not increase ventilation effectiveness. Furthermore, an extensive literature review indicates that not every exposure to an infectious agent will necessarily cause a recipient infection. The results of this study suggest a hypothesis that in an enclosed and mechanically ventilated room (e.g., an isolation room), the dominant factor that affects the transmission and control of contaminants is the path between the contaminant source and exhaust. Contaminants are better controlled when this path is uninterrupted by an air stream. This study illustrates that the ventilation system design, i.e., when it conforms with the hypothesized path principle, may be a more important factor than flow rate (i.e., ACH). A secondary factor includes the distance from the contaminant source. This study provides evidence and supports previous studies that moving away from the patient generally reduces the infection risk in a transient (coughing) situation, although the effect is more pronounced under higher flow rate. It is noted that future research is needed to determine the exact mode of transmission for most recently identified organisms.
C1 [Memarzadeh, Farhad; Xu, Weiran] NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA.
RP Memarzadeh, F (reprint author), NIH, Dept Hlth & Human Serv, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM fm30c@nih.gov
NR 64
TC 8
Z9 8
U1 1
U2 19
PU TSINGHUA UNIV PRESS
PI BEIJING
PA TSINGHUA UNIV, RM A703, XUEYAN BLDG, BEIJING, 10084, PEOPLES R CHINA
SN 1996-3599
J9 BUILD SIMUL-CHINA
JI Build. Simul.
PD MAR
PY 2012
VL 5
IS 1
BP 15
EP 28
DI 10.1007/s12273-011-0053-4
PG 14
WC Thermodynamics; Construction & Building Technology
SC Thermodynamics; Construction & Building Technology
GA 909LW
UT WOS:000301567000004
ER
PT J
AU Pazmino, PA
AF Pazmino, Patricio A.
TI Dabigatran
SO CLEVELAND CLINIC JOURNAL OF MEDICINE
LA English
DT Letter
C1 Nephrol Internal Med & Hypertens NIH Ctr, El Paso, TX USA.
RP Pazmino, PA (reprint author), Nephrol Internal Med & Hypertens NIH Ctr, El Paso, TX USA.
NR 6
TC 1
Z9 1
U1 0
U2 0
PU CLEVELAND CLINIC
PI CLEVELAND
PA 9500 EUCLID AVE, CLEVELAND, OH 44106 USA
SN 0891-1150
J9 CLEV CLIN J MED
JI Clevel. Clin. J. Med.
PD MAR
PY 2012
VL 79
IS 3
BP 166
EP 166
DI 10.3949/ccjm.79c:03003
PG 1
WC Medicine, General & Internal
SC General & Internal Medicine
GA 907FK
UT WOS:000301403000004
ER
PT J
AU Chapman, AB
Bost, JE
Torres, VE
Guay-Woodford, L
Bae, KT
Landsittel, D
Li, J
King, BF
Martin, D
Wetzel, LH
Lockhart, ME
Harris, PC
Moxey-Mims, M
Flessner, M
Bennett, WM
Grantham, JJ
AF Chapman, Arlene B.
Bost, James E.
Torres, Vicente E.
Guay-Woodford, Lisa
Bae, Kyongtae Ty
Landsittel, Douglas
Li, Jie
King, Bernard F.
Martin, Diego
Wetzel, Louis H.
Lockhart, Mark E.
Harris, Peter C.
Moxey-Mims, Marva
Flessner, Mike
Bennett, William M.
Grantham, Jared J.
TI Kidney Volume and Functional Outcomes in Autosomal Dominant Polycystic
Kidney Disease
SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY
LA English
DT Article
ID DIETARY-PROTEIN RESTRICTION; RENAL-DISEASE; COMPUTED-TOMOGRAPHY;
PROGRESSION; GROWTH; ADPKD; DETERMINANTS; SIROLIMUS; COHORT; RISK
AB Background and objectives Autosomal dominant polycystic kidney disease (ADPKD) is characterized by increased total kidney volume (TKV) and renal failure. This study aimed to determine if height-adjusted TKV (htTKV) predicts the onset of renal insufficiency.
Design, setting, participants, & measurements This prospective, observational, longitudinal, multicenter study included 241 adults with ADPKD and preserved renal function. Magnetic resonance imaging and iothalamate clearance were used to measure htTKV and GFR, respectively. The association between baseline htTKV and the attainment of stage 3 CKD (GFR <60 ml /min per 1.73 m(2)) during follow-up was determined.
Results After a mean follow-up of 7.9 years, stage 3 CKD was attained in 30.7% of the enrollees. Using baseline htTKV, negative correlations with GFR increased from -0.22 at baseline to -0.65 at year 8. In multivariable analysis, a baseline htTKV increase of 100 cc/m significantly predicted the development of CKD within 8 years with an odds ratio of 1.48 (95% confidence interval: 1.29, 1.70). In receiver operator characteristic curve analysis, baseline htTKV of 600 cc/m most accurately defined the risk of developing stage 3 CKD within 8 years with an area under the curve of 0.84 (95% confidence interval: 0.79, 0.90). htTKV was a better predictor than baseline age, serum creatinine, BUN, urinary albumin, or monocyte chemotactic protein-1 excretion (P<0.05).
Conclusions Baseline htTKV 600 cc/m predicted the risk of developing renal insufficiency in ADPKD patients at high risk for renal disease progression within 8 years of follow-up, qualifying htTKV as a prognostic biomarker in ADPKD. Clin J Am Soc Nephrol 7: 479-486, 2012. doi: 10.2215/CJN.09500911
C1 [Chapman, Arlene B.; Martin, Diego] Emory Univ, Sch Med, Atlanta, GA 30322 USA.
[Bost, James E.; Bae, Kyongtae Ty; Landsittel, Douglas; Li, Jie] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA.
[Torres, Vicente E.; King, Bernard F.; Harris, Peter C.] Mayo Coll Med, Rochester, MN USA.
[Guay-Woodford, Lisa; Lockhart, Mark E.] Univ Alabama Birmingham, Birmingham, AL USA.
[Wetzel, Louis H.; Grantham, Jared J.] Univ Kansas, Med Ctr, Kansas City, KS 66103 USA.
[Moxey-Mims, Marva; Flessner, Mike] NIDDK, NIH, Bethesda, MD USA.
[Bennett, William M.] Legacy Good Samaritan Hosp, Portland, OR USA.
RP Chapman, AB (reprint author), Emory Univ, Sch Med, 1364 Clifton Rd,Suite GG23, Atlanta, GA 30322 USA.
EM Arlene_chapman@emory.org
FU National Institute of Diabetes and Digestive and Kidney Diseases of the
National Institutes of Health [DK056943, DK056956, DK056957, DK056961];
National Center for Research Resources General Clinical Research Centers
[RR000039, RR00585, R1223940, RR000052]; Otsuka Corporation; National
Center for Research Resources [RR025008, RR024150, RR033179, R12025777,
R12024153]
FX The CRISP study is supported by cooperative agreements from the National
Institute of Diabetes and Digestive and Kidney Diseases of the National
Institutes of Health (DK056943, DK056956, DK056957, DK056961) and by the
National Center for Research Resources General Clinical Research Centers
at each institution (RR000039, Emory University; RR00585, Mayo College
of Medicine; R1223940, Kansas University Medical Center; RR000052,
University of Alabama at Birmingham) and the National Center for
Research Resources Clinical and Translational Science Awards at each
institution (RR025008, Emory; RR024150, Mayo College of Medicine;
RR033179, Kansas University Medical Center; R12025777, University of
Alabama at Birmingham; R12024153, University of Pittsburgh School of
Medicine).; A.B.C. and J.J.G. are consultants to Otsuka Corporation, and
V.E.T. received research support from Otsuka Corporation.
NR 35
TC 98
Z9 99
U1 0
U2 11
PU AMER SOC NEPHROLOGY
PI WASHINGTON
PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA
SN 1555-9041
J9 CLIN J AM SOC NEPHRO
JI Clin. J. Am. Soc. Nephrol.
PD MAR
PY 2012
VL 7
IS 3
BP 479
EP 486
DI 10.2215/CJN.09500911
PG 8
WC Urology & Nephrology
SC Urology & Nephrology
GA 904TZ
UT WOS:000301222100017
PM 22344503
ER
PT J
AU Ghiorzo, P
Pensotti, V
Fornarini, G
Sciallero, S
Battistuzzi, L
Belli, F
Bonelli, L
Borgonovo, G
Bruno, W
Gozza, A
Gargiulo, S
Mastracci, L
Nasti, S
Palmieri, G
Papadia, F
Pastorino, L
Russo, A
Savarino, V
Varesco, L
Bernard, L
Scarra, GB
AF Ghiorzo, P.
Pensotti, V.
Fornarini, G.
Sciallero, S.
Battistuzzi, L.
Belli, F.
Bonelli, L.
Borgonovo, G.
Bruno, W.
Gozza, A.
Gargiulo, S.
Mastracci, L.
Nasti, S.
Palmieri, G.
Papadia, F.
Pastorino, L.
Russo, A.
Savarino, V.
Varesco, L.
Bernard, L.
Scarra, G. Bianchi
CA Genoa Pancreatic Canc Study Grp
TI Contribution of germline mutations in the BRCA and PALB2 genes to
pancreatic cancer in Italy
SO FAMILIAL CANCER
LA English
DT Article
DE Pancreatic cancer susceptibility; BRCA; PALB2; Hereditary breast ovarian
cancer syndrome (HBOC); Germline mutation
ID ADENOCARCINOMA; POLYMERASE; INHIBITOR; FAMILIES; BREAST; RISK
AB Pancreatic adenocarcinoma (PC) is the third most common cancer associated with BRCA mutations. Most notice has been given to BRCA2, while the association between BRCA1 and PC is less widely reported. Recently, PALB2 has been implicated in both PC and breast cancer (BC) susceptibility. We selected 29 Italian PC patients from a case-control study of PC according to their personal and family history of both PC and breast/ovarian cancer (BC/OC) and tested them for presence of germline mutations in BRCA1, BRCA2 and PALB2. We identified no germline mutations or deletions in PALB2, but detected 7 BRCA mutations (4 in BRCA1 and 3 in BRCA2). These findings suggest that PALB2 does not play a major role in PC susceptibility in our population. As we found an almost equal frequency of germline mutations in BRCA1 and BRCA2, germline alterations in either of these genes may explain a subset of Italian families presenting both PC and BC/OC. Moreover, as we began the observation of these families from probands who are affected by PC, we provide here a direct assessment of the role of PALB2 and BRCA mutations in PC susceptibility.
C1 [Ghiorzo, P.; Bruno, W.; Gargiulo, S.; Nasti, S.; Pastorino, L.; Scarra, G. Bianchi] Univ Genoa, Dept Oncol Biol & Genet, I-16129 Genoa, Italy.
[Pensotti, V.] FIRC Inst Mol Oncol Fdn IFOM, Milan, Italy.
[Fornarini, G.; Sciallero, S.] San Martino Hosp, Med Oncol Unit, Genoa, Italy.
[Battistuzzi, L.] Univ Genoa, Dept Hlth Sci, I-16129 Genoa, Italy.
[Belli, F.] Galliera Hosp, Gen & Biliopancreat Surg Unit, Genoa, Italy.
[Bonelli, L.] Natl Canc Inst, I-20133 Milan, Italy.
[Borgonovo, G.; Papadia, F.] Univ Genoa, Dept Surg, I-16129 Genoa, Italy.
[Gozza, A.] Galliera Hosp, Med Oncol Unit, Genoa, Italy.
[Mastracci, L.] Univ Genoa, Dept Anat Pathol, I-16129 Genoa, Italy.
[Palmieri, G.] CNR, Inst Biomol Chem, Sassari, Italy.
[Russo, A.] Univ Palermo, Dept Surg & Oncol, Palermo, Italy.
[Savarino, V.] Univ Genoa, Dept Internal Med, I-16129 Genoa, Italy.
[Varesco, L.] Natl Canc Inst, Ctr Hereditary Tumors, Genoa, Italy.
[Bernard, L.] European Inst Oncol, Dept Expt Oncol, Milan, Italy.
[Scarra, G. Bianchi] San Martino Hosp, Lab Rare Hereditary Canc, Genoa, Italy.
RP Ghiorzo, P (reprint author), Univ Genoa, Dept Oncol Biol & Genet, Vle Benedetto 15,6, I-16129 Genoa, Italy.
EM paola.ghiorzo@unige.it
RI Bianchi Scarra, Giovanna/G-8933-2014; Bernard, Loris/K-5953-2014; Bruno,
William/N-7477-2013;
OI Bianchi Scarra, Giovanna/0000-0002-6127-1192; Bruno,
William/0000-0002-0337-0168; Mastracci, Luca/0000-0003-0193-5281;
Palmieri, Giuseppe/0000-0002-4350-2276
FU IRCSS Italian Ministry of Health [DGRST.4/4235-P1.9.A.B]; Fondazione
CARIGE
FX We are grateful to Chiara Baldo at the Galliera Genetic Bank-Network of
Telethon Genetic Biobanks (project GTB07001) for providing
lymphoblastoid cell-lines. This study was funded by IRCSS 2007 Italian
Ministry of Health DGRST.4/4235-P1.9.A.B, Fondazione CARIGE, PRIN 2008
to G.B.-S.
NR 31
TC 13
Z9 13
U1 0
U2 4
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 1389-9600
J9 FAM CANCER
JI Fam. Cancer
PD MAR
PY 2012
VL 11
IS 1
BP 41
EP 47
DI 10.1007/s10689-011-9483-5
PG 7
WC Oncology; Genetics & Heredity
SC Oncology; Genetics & Heredity
GA 908RR
UT WOS:000301508300007
PM 21989927
ER
PT J
AU Schoen, RE
Pinsky, PF
Weissfeld, JL
Yokochi, LA
Church, T
Laiyemo, AO
Bresalier, R
Hickey, T
Riley, T
Prorok, PC
AF Schoen, Robert E.
Pinsky, Paul F.
Weissfeld, Joel L.
Yokochi, Lance A.
Church, Timothy
Laiyemo, Adeyinka O.
Bresalier, Robert
Hickey, Tom
Riley, Thomas
Prorok, Philip C.
TI Colorectal cancers not detected by screening flexible sigmoidoscopy in
the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial
SO GASTROINTESTINAL ENDOSCOPY
LA English
DT Article
ID NEGATIVE COLONOSCOPY; ADENOMA DETECTION; SURVEILLANCE; RISK; PROTECTION;
PREDICTORS; COLON; RATES; SITE; AGE
AB Background and Objective: Diagnosis of colorectal cancer after negative findings on endoscopic evaluation raises concern about the effectiveness of endoscopic screening. We contrast screening-detected cancers with cancers not detected by screening among participants assigned to flexible sigmoidoscopy (FSG) in the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial to determine the reasons for the lack of detection of prevalent lesions.
Design: Cancers detected within 1 year of a screening FSG with abnormal findings were classified as screening detected. All other cancers were categorized, based on cancer stage and years until detection, as either not detectable or prevalent but not detected at the time of screening.
Setting/Patients: A total of 77,447 subjects in the multicenter PLCO trial.
Main Outcome Measurements: A total of 977 colorectal cancers were diagnosed with a mean follow-up of 11.5 years.
Results: A total of 243 (24.9%) cancers were screening detected, 470 (48.1%) were not detectable at screening, and 264 (27.0%) were considered prevalent but not detected. Among prevalent nondetected lesions, 35.6% (n = 94) were attributed to problems in patient compliance (58 never screened, 34 delayed colonoscopy follow-up, and 2 inadequate bowel preparation), 43.9% (n = 116) were attributable to a limitation in the FSG procedure (97 beyond the reach of the sigmoidoscope and 19 inadequate depth of insertion on FSG), and 20.5% (n = 54) were caused by endoscopist limitation (33 missed on FSG, 21 missed at initial colonoscopy) (P < .0001). Had colonoscopy instead of FSG been used for screening, an additional 15.6% and as many as 19.0% of cancers may have been screening-detected.
Limitations: These estimates are reasonable approximations, but biological variability precludes precise determinations.
Conclusions: Prevalent nondetected cancers were more often attributable to problems with patient compliance or limitations in the FSG procedure than to missed lesions. Colonoscopy instead of FSG could have moderately increased the detection of cancer via screening. (Gastrointest Endosc 2012;75:612-20.)
C1 [Schoen, Robert E.] Univ Pittsburgh, Inst Canc, Dept Med, Div Gastroenterol Hepatol & Nutr,PUH, Pittsburgh, PA 15213 USA.
[Schoen, Robert E.; Weissfeld, Joel L.] Univ Pittsburgh, Inst Canc, Dept Epidemiol, Pittsburgh, PA 15213 USA.
[Pinsky, Paul F.; Prorok, Philip C.] NCI, Canc Prevent Div, Bethesda, MD 20892 USA.
[Yokochi, Lance A.] Pacific Hlth Res & Educ Inst, Honolulu, HI USA.
[Church, Timothy] Univ Minnesota, Dept Hlth Studies Environm Hlth Sci, Minneapolis, MN USA.
[Laiyemo, Adeyinka O.] Howard Univ, Washington, DC 20059 USA.
[Bresalier, Robert] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA.
[Hickey, Tom; Riley, Thomas] Informat Management Serv Inc, Rockville, MD USA.
RP Schoen, RE (reprint author), Univ Pittsburgh, Inst Canc, Dept Med, Div Gastroenterol Hepatol & Nutr,PUH, C Wing,200 Lothrop St, Pittsburgh, PA 15213 USA.
EM rschoen@pitt.edu
OI Church, Timothy R./0000-0003-3292-5035
FU National Cancer Institute [N01-CN-25511, N01-CN-25513, N01-CN-25515]
FX The authors disclosed no financial relationships relevant to this
publication. Supported by contracts from the National Cancer Institute:
N01-CN-25511 to University of Pittsburgh Cancer Institute (RES, JLW),
N01-CN-25513 to University of Minnesota School of Public Health (TG),
N01-CN-25515 to Pacific Health Research & Education Institute (LAY).
NR 35
TC 14
Z9 15
U1 0
U2 3
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0016-5107
J9 GASTROINTEST ENDOSC
JI Gastrointest. Endosc.
PD MAR
PY 2012
VL 75
IS 3
BP 612
EP 620
DI 10.1016/j.gie.2011.10.024
PG 9
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 906BM
UT WOS:000301319900024
PM 22341106
ER
PT J
AU Yu, CH
Bonaduce, MJ
Klar, AJS
AF Yu, Chuanhe
Bonaduce, Michael J.
Klar, Amar J. S.
TI Going in the Right Direction: Mating-Type Switching of
Schizosaccharomyces pombe Is Controlled by Judicious Expression of Two
Different swi2 Transcripts
SO GENETICS
LA English
DT Article
ID DOUBLE-STRAND BREAKS; FISSION YEAST; CENP-B; S-POMBE; CHROMOSOME
SEGREGATION; SEX DETERMINATION; DNA STRANDS; RECOMBINATION; PROTEIN;
HETEROCHROMATIN
AB Schizosaccharomyces pombe, the fission yeast, cells alternate between P-and M-mating type, controlled by the alternate alleles of the mating-type locus (mat1). The mat1 switching occurs by replacing mat1 with a copy derived from a silenced "donor locus," mat2P or mat3M. The mechanism of donor choice ensuring that switching occurs primarily and productively to the opposite type, called directionality, is largely unknown. Here we identified the mat1-Mc gene, a mammalian sex-determination gene (SRY) homolog, as the primary gene that dictates directionality in M cells. A previously unrecognized, shorter swi2 mRNA, a truncated form of the swi2, was identified, and its expression requires the mat1-Mc function. We also found that the abp1 gene (human CENPB homolog) controls directionality through swi2 regulation. In addition, we implicated a cis-acting DNA sequence in mat2 utilization. Overall, we showed that switching directionality is controlled by judicious expression of two swi2 transcripts through a cell-type-regulated dual promoter. In this respect, this regulation mechanism resembles that of the Drosophila sex-determination Slx gene.
C1 [Yu, Chuanhe; Bonaduce, Michael J.; Klar, Amar J. S.] NCI, Dev Genet Sect, Gene Regulat & Chromosome Biol Lab, NIH, Frederick, MD 21702 USA.
RP Klar, AJS (reprint author), NCI, Dev Genet Sect, Gene Regulat & Chromosome Biol Lab, NIH, Frederick, MD 21702 USA.
EM klara@mail.nih.gov
FU National Cancer Institute of the National Institutes of Health
FX We thank Sharon Moore, Ken Ishikawa, Stephan Sauer, and Jeff Strathern's
laboratory members for discussions and advice. We also thank Drs.
Fernando Azorin and Hiroshi Iwasaki for providing yeast strains. The
Intramural Research Program of the National Cancer Institute of the
National Institutes of Health supported this work. C.Y. and A. K.
designed and performed the experiments, analyzed the data, and wrote the
manuscript; M. B. provided technical support for this work. The authors
declare that they have no conflict of interest.
NR 52
TC 4
Z9 4
U1 1
U2 9
PU GENETICS SOCIETY AMERICA
PI BETHESDA
PA 9650 ROCKVILLE AVE, BETHESDA, MD 20814 USA
SN 0016-6731
EI 1943-2631
J9 GENETICS
JI Genetics
PD MAR
PY 2012
VL 190
IS 3
BP 977
EP U182
DI 10.1534/genetics.111.137109
PG 14
WC Genetics & Heredity
SC Genetics & Heredity
GA 908ZP
UT WOS:000301531900010
PM 22209903
ER
PT J
AU Diao, FQ
White, BH
AF Diao, Fengqiu
White, Benjamin H.
TI A Novel Approach for Directing Transgene Expression in Drosophila:
T2A-Gal4 In-Frame Fusion
SO GENETICS
LA English
DT Article
ID COURTSHIP BEHAVIOR; MELANOGASTER; VERSATILE; RECEPTOR; INSERTION;
PROTEINS; RESOURCE; VECTORS; DISEASE; CELLS
AB In Drosophila, the Gal4-UAS system permits a transgene to be expressed in the same pattern as a gene of interest by placing the Gal4 transcription factor under control of the gene's DNA regulatory elements. If these regulatory elements are not known, however, expression of Gal4 in the desired pattern may be difficult or impossible. To solve this problem, we have developed a method for co-expressing Gal4 with the endogenous gene by exploiting the "ribosomal skipping" mechanism of the viral T2A peptide. This method requires explicit knowledge only of the endogenous gene's open reading frame and not its regulatory elements.
C1 [Diao, Fengqiu; White, Benjamin H.] NIMH, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
RP White, BH (reprint author), NIMH, Mol Biol Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM benjaminwhite@mail.nih.gov
FU National Institute of Mental Health [1ZIA-MH-002800-07]
FX We thank Bruce Paterson and Chi-hon Lee for the pPacPL and pC-attB
plasmids, respectively; Randall Hewes for UAS-dnc flies; and the
National Institute of Neurological Disorders and Stroke DNA sequencing
facility for sequencing services. We also thank Grace Gray for comments
on the manuscript. This research was supported by the Intramural
Research Program of the National Institute of Mental Health (Project
1ZIA-MH-002800-07).
NR 23
TC 23
Z9 23
U1 0
U2 7
PU GENETICS SOC AM
PI BETHESDA
PA 9650 ROCKVILLE AVE, BETHESDA, MD 20814 USA
SN 0016-6731
J9 GENETICS
JI Genetics
PD MAR
PY 2012
VL 190
IS 3
BP 1139
EP U356
DI 10.1534/genetics.111.136291
PG 13
WC Genetics & Heredity
SC Genetics & Heredity
GA 908ZP
UT WOS:000301531900022
PM 22209908
ER
PT J
AU Bush, LW
Rothenberg, KH
AF Bush, Lynn W.
Rothenberg, Karen H.
TI Dialogues, dilemmas, and disclosures: genomic research and incidental
findings
SO GENETICS IN MEDICINE
LA English
DT Editorial Material
ID PARTICIPANTS
C1 [Bush, Lynn W.] Columbia Univ, Dept Pediat, Div Clin Genet, New York, NY 10027 USA.
[Rothenberg, Karen H.] Univ Maryland, Francis King Carey Sch Law, Baltimore, MD 21201 USA.
[Rothenberg, Karen H.] NHGRI, Bethesda, MD 20892 USA.
[Rothenberg, Karen H.] NIH, Dept Bioeth, Ctr Clin, Bethesda, MD 20892 USA.
RP Bush, LW (reprint author), Columbia Univ, Dept Pediat, Div Clin Genet, New York, NY 10027 USA.
EM lwb25@columbia.edu
NR 10
TC 4
Z9 4
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1098-3600
J9 GENET MED
JI Genet. Med.
PD MAR
PY 2012
VL 14
IS 3
BP 293
EP 295
DI 10.1038/gim.2011.72
PG 3
WC Genetics & Heredity
SC Genetics & Heredity
GA 908FF
UT WOS:000301475100002
PM 22391780
ER
PT J
AU Handel, EM
Gellhaus, K
Khan, K
Bednarski, C
Cornu, TI
Muller-Lerch, F
Kotin, RM
Heilbronn, R
Cathomen, T
AF Haendel, Eva-Maria
Gellhaus, Katharina
Khan, Kafaitullah
Bednarski, Christien
Cornu, Tatjana I.
Mueller-Lerch, Felix
Kotin, Robert M.
Heilbronn, Regine
Cathomen, Toni
TI Versatile and Efficient Genome Editing in Human Cells by Combining
Zinc-Finger Nucleases With Adeno-Associated Viral Vectors
SO HUMAN GENE THERAPY
LA English
DT Article
ID DOUBLE-STRAND BREAKS; TARGETED GENE ADDITION; IN-VIVO; VIRUS VECTORS;
STEM-CELLS; HOMOLOGOUS RECOMBINATION; MAJOR DETERMINANT; INSECT CELLS;
TRANSDUCTION; SPECIFICITY
AB Zinc-finger nucleases (ZFNs) have become a valuable tool for targeted genome engineering. Based on the enzyme's ability to create a site-specific DNA double-strand break, ZFNs promote genome editing by activating the cellular DNA damage response, including homology-directed repair (HDR) and nonhomologous end-joining. The goal of this study was (i) to demonstrate the versatility of combining the ZFN technology with a vector platform based on adeno-associated virus (AAV), and (ii) to assess the toxicity evoked by this platform. To this end, human cell lines that harbor enhanced green fluorescence protein (EGFP) reporters were generated to easily quantify the frequencies of gene deletion, gene disruption, and gene correction. We demonstrated that ZFN-encoding AAV expression vectors can be employed to induce large chromosomal deletions or to disrupt genes in up to 32% of transduced cells. In combination with AAV vectors that served as HDR donors, the AAV-ZFN platform was utilized to correct a mutation in EGFP in up to 6% of cells. Genome editing on the DNA level was confirmed by genotyping. Although cell cycle profiling revealed a modest G2/M arrest at high AAV-ZFN vector doses, platform-induced apoptosis could not be detected. In conclusion, the combined AAV-ZFN vector technology is a useful tool to edit the human genome with high efficiency. Because AAV vectors can transduce many cell types relevant for gene therapy, the ex vivo and in vivo delivery of ZFNs via AAV vectors will be of great interest for the treatment of inherited disorders.
C1 [Haendel, Eva-Maria; Khan, Kafaitullah; Bednarski, Christien; Cathomen, Toni] Hannover Med Sch, Inst Expt Hematol, D-30625 Hannover, Germany.
[Haendel, Eva-Maria; Gellhaus, Katharina; Khan, Kafaitullah; Bednarski, Christien; Cornu, Tatjana I.; Mueller-Lerch, Felix; Heilbronn, Regine; Cathomen, Toni] Charite, Inst Virol, D-12203 Berlin, Germany.
[Kotin, Robert M.] NHLBI, Mol Virol & Gene Delivery Sect, Lab Biochem Genet, NIH, Bethesda, MD 20892 USA.
RP Cathomen, T (reprint author), Hannover Med Sch, Inst Expt Hematol, Carl Neuberg Str 1, D-30625 Hannover, Germany.
EM cathomen.toni@mh-hannover.de
RI Heilbronn, Regine/E-1349-2013;
OI Cathomen, Toni/0000-0002-7757-4630
FU German Ministry of Education and Research [ITCF-01GU0618]; European
Commission [PERSIST-222878]; German Research Foundation [SFB/TR19-TPC5];
German Academic Exchange Service (DAAD)
FX We thank Jessica Wenzl and Eva Guhl for technical assistance, Shamim H.
Rahman and Sylwia Bobis-Wozowicz for help with experiments and critical
discussions, and Nicholas Muzyczka for plasmids. This work was supported
by grants ITCF-01GU0618 of the German Ministry of Education and
Research, PERSIST-222878 of the European Commission's 7th Framework
Programme, and SFB/TR19-TPC5 of the German Research Foundation to T.C.,
and a fellowship of the German Academic Exchange Service (DAAD) to K.K.
NR 55
TC 37
Z9 37
U1 0
U2 8
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 1043-0342
J9 HUM GENE THER
JI Hum. Gene Ther.
PD MAR
PY 2012
VL 23
IS 3
BP 321
EP 329
DI 10.1089/hum.2011.140
PG 9
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 906PO
UT WOS:000301359100010
PM 21980922
ER
PT J
AU Kaess, BM
Pedley, A
Massaro, JM
Larson, MG
Corsini, E
Hoffmann, U
Smith, HM
Sawyer, DB
Vasan, RS
Fox, CS
AF Kaess, Bernhard M.
Pedley, Alison
Massaro, Joseph M.
Larson, Martin G.
Corsini, Erin
Hoffmann, Udo
Smith, Holly M.
Sawyer, Douglas B.
Vasan, Ramachandran S.
Fox, Caroline S.
TI Relation of Vascular Growth Factors with CT-Derived Measures of Body Fat
Distribution: The Framingham Heart Study
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID ACUTE MYOCARDIAL-INFARCTION; SOLUBLE RECEPTOR SFLT-1; DISEASE
RISK-FACTORS; ADIPOSE-TISSUE; GENE-EXPRESSION; BREAST-CANCER;
PLASMA-LEVELS; OBESITY; ASSOCIATION; ADIPOCYTES
AB Background: Visceral adiposity is associated with metabolic risk. Given that angiogenesis is a key feature of adipogenesis, variation in the association of levels of circulating vascular growth factors (and their soluble receptors) with distinct body fat compartments may explain differences in the systemic pathogenicity of regional fat depots.
Methods and Results: Four body fat compartments [visceral adipose tissue (VAT), sc adipose tissue (SAT), thoracic periaortic fat, and pericardial fat] derived from computed tomography were related to serum concentrations of vascular endothelial growth factor (VEGF), the soluble VEGF receptor (fms-like tyrosine kinase-1), hepatocyte growth factor (HGF), and angiopoietin-2 and its soluble receptor (soluble tyrosine kinase with immunoglobulin-like and EGF-like domains 2 sTie-2) in 1806 Framingham Heart Study participants (mean age 44.9 yr, 44.5% women). In multivariable models, we observed positive associations between several fat compartments and VEGF and HGF levels. The magnitude of the associations were similar for VAT, SAT, and periaortic fat. We observed effect modification by sex. A stronger association was observed between VAT and HGF levels in women; higher VAT and periaortic fat were jointly associated with higher HGF concentrations (P = 0.02 and P = 0.051, respectively). In women within the highest tertile of VAT, HGF levels significantly increased with higher periaortic fat (P = 0.0005).
Conclusions: In our large community-based sample, greater adiposity was associated with higher circulating growth factor levels in general. Additional studies are warranted to confirm the stronger association of VAT and periaortic fat with HGF in women and to examine its potential contribution to the sex-related differences in cardiometabolic risk. (J Clin Endocrinol Metab 97: 987-994, 2012)
C1 [Kaess, Bernhard M.; Pedley, Alison; Larson, Martin G.; Vasan, Ramachandran S.; Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA.
[Kaess, Bernhard M.] Univ Regensburg, Dept Internal Med 2, D-93053 Regensburg, Germany.
[Massaro, Joseph M.; Larson, Martin G.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA.
[Larson, Martin G.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA.
[Vasan, Ramachandran S.] Boston Univ, Dept Med, Prevent Med & Epidemiol Sect, Boston, MA 02215 USA.
[Vasan, Ramachandran S.] Boston Univ, Dept Med, Cardiol Sect, Boston, MA 02215 USA.
[Corsini, Erin; Hoffmann, Udo] Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA.
[Hoffmann, Udo; Fox, Caroline S.] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Fox, Caroline S.] Brigham & Womens Div Endocrinol Hypertens & Metab, Boston, MA 02115 USA.
[Smith, Holly M.; Sawyer, Douglas B.] Vanderbilt Univ, Div Cardiovasc, Nashville, TN 37232 USA.
RP Fox, CS (reprint author), 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA.
EM foxca@nhlbi.nih.gov
OI Massaro, Joseph/0000-0002-2682-4812; Larson, Martin/0000-0002-9631-1254;
Ramachandran, Vasan/0000-0001-7357-5970
FU National Institutes of Health National Heart, Lung, and Blood Institute
[N01-HC-25195, RO1-HL-077477]
FX This work was supported by National Institutes of Health National Heart,
Lung, and Blood Institute Contract N01-HC-25195 and RO1-HL-077477 (to
R.S.V.).
NR 48
TC 8
Z9 8
U1 0
U2 0
PU ENDOCRINE SOC
PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0021-972X
J9 J CLIN ENDOCR METAB
JI J. Clin. Endocrinol. Metab.
PD MAR
PY 2012
VL 97
IS 3
BP 987
EP 994
DI 10.1210/jc.2011-2310
PG 8
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 904WM
UT WOS:000301229600065
PM 22170711
ER
PT J
AU Patronas, Y
Horvath, A
Greene, E
Tsang, K
Bimpaki, E
Haran, M
Nesterova, M
Stratakis, CA
AF Patronas, Yianna
Horvath, Anelia
Greene, Elizabeth
Tsang, Kitman
Bimpaki, Eirini
Haran, Michelle
Nesterova, Maria
Stratakis, Constantine A.
TI In Vitro Studies of Novel PRKAR1A Mutants that Extend the Predicted RI
alpha Protein Sequence into the 3 '-Untranslated Open Reading Frame:
Proteasomal Degradation Leads to RI alpha Haploinsufficiency and Carney
Complex
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID ABERRANT MESSENGER-RNAS; REGULATORY SUBUNIT; MUTATIONS; GENE; PHENOTYPE;
DISEASE; PATIENT
AB Background: Carney complex (CNC) is a multiple endocrine neoplasia syndrome due to inactivating mutations in the PRKAR1A gene that codes for type I alpha regulatory (RI alpha) subunit of protein kinase A. Most PRKAR1A mutations are subject to nonsense mRNA decay (NMD) and, thus, lead to haploinsufficiency.
Methods and Setting: Patient phenotyping for CNC features and DNA, RNA, protein, and transfection studies were carried out at a research center.
Results: We describe in unrelated kindreds with CNC four naturally occurring PRKAR1A mutations (1055del4, 1067del4ins5, 1076delTTins13, and1142del4) that are predicted to escape NMD because they are located in the last coding exon of the gene. The phenotype of CNC was not different from that in other patients with the condition, although the number of patients was small. Each of the mutations caused a frameshift that led to a new stop codon into the 3' untranslated open reading frame, predicting an elongated protein that, however, was absent in patient-derived cells. After site-directed mutagenesis, in vitro transcription, and cell-free translation experiments, the expected size mutant proteins were present. However, when the mutant constructs were transfected in adrenal (NCI-295), testicular (N-TERA), and embryonic (HEK293) cells and despite the presence of the mutant mRNA, Western blot analysis indicated that there were no longer proteins. The subsequent application of proteasome inhibitors to cells transfected with the mutant constructs led to the detection of the aberrant proteins, although a compound that affects protein folding had no effect. The wild-type protein was also decreased in both patient-derived cells and/or tissues as well as in the in vitro systems used in this study.
Conclusions: This was the first demonstration of proteasomal degradation of RI alpha protein variants leading to PRKAR1A haploinsufficiency and CNC, adding protein surveillance to NMD in the cellular mechanisms overseeing RI alpha synthesis. In agreement with the molecular data, CNC patients bearing PRKAR1A defects that extend the open reading frame did not have a different phenotype, although this has to be confirmed in a larger number of patients. (J Clin Endocrinol Metab 97: E496-E502, 2012)
C1 [Patronas, Yianna; Horvath, Anelia; Greene, Elizabeth; Tsang, Kitman; Bimpaki, Eirini; Haran, Michelle; Nesterova, Maria; Stratakis, Constantine A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrinol Genet, Program Dev Endocrinol & Genet, NIH,Clin Ctr, Bethesda, MD 20892 USA.
[Stratakis, Constantine A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pediat Endocrinol Interinst Training Program, NIH, Ctr Clin, Bethesda, MD 20892 USA.
RP Stratakis, CA (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrinol Genet, Program Dev Endocrinol & Genet, NIH,Clin Ctr, Bldg 10,CRC,Room 1-3330,10 Ctr Dr,MSC1103, Bethesda, MD 20892 USA.
EM stratakc@mail.nih.gov
RI Leyla, Sozaeva/C-7231-2012
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development, Intramural National Institutes of Health [Z01-HD-000642-04]
FX This work was supported by the Eunice Kennedy Shriver National Institute
of Child Health and Human Development, Intramural National Institutes of
Health Project Z01-HD-000642-04 to C.A.S.
NR 19
TC 9
Z9 9
U1 0
U2 0
PU ENDOCRINE SOC
PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0021-972X
J9 J CLIN ENDOCR METAB
JI J. Clin. Endocrinol. Metab.
PD MAR
PY 2012
VL 97
IS 3
BP E496
EP E502
DI 10.1210/jc.2011-2220
PG 7
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 904WM
UT WOS:000301229600024
PM 22205709
ER
PT J
AU Xekouki, P
Pacak, K
Almeida, M
Wassif, CA
Rustin, P
Nesterova, M
Sierra, MD
Matro, J
Ball, E
Azevedo, M
Horvath, A
Lyssikatos, C
Quezado, M
Patronas, N
Ferrando, B
Pasini, B
Lytras, A
Tolis, G
Stratakis, CA
AF Xekouki, Paraskevi
Pacak, Karel
Almeida, Madson
Wassif, Christopher A.
Rustin, Pierre
Nesterova, Maria
Sierra, Maria de la Luz
Matro, Joey
Ball, Evan
Azevedo, Monalisa
Horvath, Anelia
Lyssikatos, Charalampos
Quezado, Martha
Patronas, Nicholas
Ferrando, Barbara
Pasini, Barbara
Lytras, Aristides
Tolis, George
Stratakis, Constantine A.
TI Succinate Dehydrogenase (SDH) D Subunit (SDHD) Inactivation in a
Growth-Hormone-Producing Pituitary Tumor: A New Association for SDH?
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID CARNEY-STRATAKIS-SYNDROME; GERMLINE MUTATIONS; COMPLEX-II; HEREDITARY
PARAGANGLIOMA; MOLECULAR-GENETICS; PHEOCHROMOCYTOMA; TUMORIGENESIS;
EXPRESSION; VARIANTS; GENES
AB Background: Mutations in the subunits B, C, and D of succinate dehydrogenase (SDH) mitochondrial complex II have been associated with the development of paragangliomas (PGL), gastrointestinal stromal tumors, papillary thyroid and renal carcinoma (SDHB), and testicular seminoma (SDHD).
Aim: Our aim was to examine the possible causative link between SDHD inactivation and somatotropinoma.
Patients and Methods: A 37-yr-old male presented with acromegaly and hypertension. Other family members were found with PGL. Elevated plasma and urinary levels of catecholamines led to the identification of multiple PGL in the proband in the neck, thorax, and abdomen. Adrenalectomy was performed for bilateral pheochromocytomas (PHEO). A GH-secreting macroadenoma was also found and partially removed via transsphenoidal surgery (TTS). Genetic analysis revealed a novel SDHD mutation (c.298_301delACTC), leading to a frame shift and a premature stop codon at position 133 of the protein. Loss of heterozygosity for the SDHD genetic locus was shown in the GH-secreting adenoma. Down-regulation of SDHD protein in the GH-secreting adenoma by immunoblotting and immunohistochemistry was found. A literature search identified other cases of multiple PGL and/or PHEO in association with pituitary tumors.
Conclusion: We describe the first kindred with a germline SDHD pathogenic mutation, inherited PGL, and acromegaly due to a GH-producing pituitary adenoma. SDHD loss of heterozygosity, down-regulation of protein in the GH-secreting adenoma, and decreased SDH enzymatic activity supports SDHD's involvement in the pituitary tumor formation in this patient. Older cases of multiple PGL and PHEO and pituitary tumors in the literature support a possible association between SDH defects and pituitary tumorigenesis. (J Clin Endocrinol Metab 97: E357-E366, 2012)
C1 [Xekouki, Paraskevi; Almeida, Madson; Nesterova, Maria; Sierra, Maria de la Luz; Ball, Evan; Azevedo, Monalisa; Horvath, Anelia; Lyssikatos, Charalampos; Stratakis, Constantine A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrinol & Genet, Bethesda, MD 20892 USA.
[Wassif, Christopher A.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Mol Dysmorphol, Bethesda, MD 20892 USA.
[Pacak, Karel; Matro, Joey] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Dev Endocrinol & Genet, Bethesda, MD 20892 USA.
[Pacak, Karel; Matro, Joey] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pediat Endocrinol Interinst Training Program, Bethesda, MD 20892 USA.
[Pacak, Karel; Matro, Joey] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Med Neuroendocrinol, Bethesda, MD 20892 USA.
Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, Bethesda, MD 20892 USA.
[Quezado, Martha] NCI, Pathol Lab, Bethesda, MD 20892 USA.
[Patronas, Nicholas] NIH, Dept Diagnost Radiol, Clin Res Ctr, Bethesda, MD 20892 USA.
[Xekouki, Paraskevi; Lytras, Aristides; Tolis, George] Hippocrate Gen Hosp, Div Endocrinol & Metab, Athens 11527, Greece.
[Rustin, Pierre] INSERM, U676, Fac Med Denis Diderot, IFR02 Paris, F-75654 Paris 13, France.
[Rustin, Pierre] Univ Paris 07, Fac Med Denis Diderot, IFR02 Paris, F-75221 Paris 05, France.
[Ferrando, Barbara; Pasini, Barbara] Univ Turin, Dept Genet Biol & Biochem, I-10126 Turin, Italy.
[Lytras, Aristides] Harvard Univ, Sch Med, Joslin Diabet Ctr, Dept Cellular & Mol Physiol, Boston, MA 02215 USA.
RP Stratakis, CA (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bldg 10,CRC,Room 1-3330,10 Ctr Dr,MSC1103, Bethesda, MD 20892 USA.
EM stratakc@mail.nih.gov
OI Wassif, Christopher/0000-0002-2524-1420
FU NICHD, NIH [Z01 HD000642-04]; Agence National de la Recherche; Hellenic
Endocrine Society, Athens, Greece
FX This work was supported by the intramural program of the NICHD, NIH
(Project Z01 HD000642-04; principal investigator C.A.S.), by the Agence
National de la Recherche (Project MitOxy; principal investigator P.R.),
and in part, by a 1-yr grant to P.X. on the molecular investigation of
pituitary tumors by the Hellenic Endocrine Society, Athens, Greece.
NR 39
TC 47
Z9 48
U1 0
U2 1
PU ENDOCRINE SOC
PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0021-972X
J9 J CLIN ENDOCR METAB
JI J. Clin. Endocrinol. Metab.
PD MAR
PY 2012
VL 97
IS 3
BP E357
EP E366
DI 10.1210/jc.2011-1179
PG 10
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 904WM
UT WOS:000301229600005
PM 22170724
ER
PT J
AU Zhang, LS
He, M
Zhang, YQ
Nilubol, N
Shen, M
Kebebew, E
AF Zhang, Lisa
He, Mei
Zhang, Yaqin
Nilubol, Naris
Shen, Min
Kebebew, Electron
TI Quantitative High-Throughput Drug Screening Identifies Novel Classes of
Drugs with Anticancer Activity in Thyroid Cancer Cells: Opportunities
for Repurposing
SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
LA English
DT Article
ID ACTIVATED-RECEPTOR-BETA/DELTA; CHEMICAL LIBRARIES; NA+/K+-ATPASE;
INHIBITION; CYCLOOXYGENASE-2; CHEMOPREVENTION; PROSTATE; LINES; RISK;
LUNG
AB Context: Despite increased understanding of the pathogenesis and targets for thyroid cancer and other cancers, developing a new anticancer chemical agent remains an expensive and long process. An alternative approach is the exploitation of clinically used and/or bioactive compounds.
Objective: Our objective was to identify agents with an anticancer effect in thyroid cancer cell lines using quantitative high-throughput screening (qHTS).
Design: We used the newly assembled National Institutes of Health Chemical Genomic Center's pharmaceutical collection, which contains 2816 clinically approved drugs and bioactive compounds to perform qHTS.
Results: Multiple agents, across a variety of therapeutic categories and with different modes of action, were found to have an antiproliferative effect. We found the following therapeutic categories were the most enriched categories with antiproliferative activity: cardiotonic and anti-obesity agents. Sixteen agents had an efficacy of greater than 60% and a 50% inhibitory concentration (IC50) in the nanomolar range. We validated the results of the qHTS using two agents (bortezomib and ouabain) in additional cell lines representing different histological subtypes of thyroid cancer and with different mutations (BRAF V600E, RET/PTC1, p53, PTEN). Both agents induced apoptosis, and ouabain also caused cell cycle arrest.
Conclusions: To our knowledge, this is the first study to use qHTS of a large drug library to identify candidate drugs for anticancer therapy. Our results indicate such a screening approach can lead to the discovery of novel agents in different therapeutic categories and drugs with nonclassic chemotherapy mode of action. Our approach could lead to drug repurposing and accelerate clinical trials of compounds with well-established pharmacokinetics and toxicity profiles. (J Clin Endocrinol Metab 97: E319-E328, 2012)
C1 [Kebebew, Electron] NCI, Endocrine Oncol Sect, Surg Branch, Clin Res Ctr, Bethesda, MD 20892 USA.
[Zhang, Yaqin; Shen, Min] NHGRI, NIH, Chem Genom Ctr, Bethesda, MD 20892 USA.
RP Kebebew, E (reprint author), NCI, Endocrine Oncol Sect, Surg Branch, Clin Res Ctr, Bldg 10 CRC,Room 3-3940,10 Ctr Dr,MSC 1201, Bethesda, MD 20892 USA.
EM kebebewe@mail.nih.gov
FU Center for Cancer Research, National Cancer Institute, National
Institutes of Health
FX This research was supported by the Intramural Research Program, Center
for Cancer Research, National Cancer Institute, National Institutes of
Health.
NR 34
TC 13
Z9 14
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
J9 J CLIN ENDOCR METAB
JI J. Clin. Endocrinol. Metab.
PD MAR
PY 2012
VL 97
IS 3
BP E319
EP E328
DI 10.1210/jc.2011-2671
PG 10
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 904WM
UT WOS:000301229600001
PM 22170715
ER
PT J
AU Ozturk, F
Park, PJ
Tellez, J
Colletti, E
Eiden, MV
Almeida-Porada, G
Porada, CD
AF Ozturk, Ferhat
Park, Paul J.
Tellez, Joseph
Colletti, Evan
Eiden, Maribeth V.
Almeida-Porada, Graca
Porada, Christopher D.
TI Expression levels of the PiT-2 receptor explain, in part, the
gestational age-dependent alterations in transduction efficiency after
in utero retroviral-mediated gene transfer
SO JOURNAL OF GENE MEDICINE
LA English
DT Article
DE fetal gene therapy; retroviral vector; transduction; developmental
regulation; PiT-2 receptor
ID APE LEUKEMIA-VIRUS; BONE-MARROW-CELLS; MURINE; VECTORS; ENGRAFTMENT;
INFECTION; THERAPY; PROTEIN; BLOOD; ENTRY
AB Background A fundamental obstacle to using retroviral-mediated gene transfer (GT) to treat human diseases is the relatively low transduction levels that have been achieved in clinically relevant human cells. We previously showed that performing GT in utero overcomes this obstacle and results in significant levels of transduction within multiple fetal organs, with different tissues exhibiting optimal transduction at different developmental stages. We undertook the present study aiming to elucidate the mechanism for this age-dependent transduction, testing the two factors that we hypothesized could be responsible: (i) the proliferative status of the tissue at the time of GT and (ii) the expression level of the amphotropic PiT-2 receptor.
Methods Immunofluorescence was performed on tissues from sheep of varying developmental stages to assess the proliferative status of the predominant cells within each organ as a function of age. After developing an enzyme-linked immunosorbent assay (ELISA) and a quantitative reverse transcription chain reaction (qRT-PCR) assay, we then quantified PiT-2 expression at the protein and mRNA levels, respectively.
Results The results obtained indicate that the proliferative status of organs at the time of fetal GT is not the major determinant governing transduction efficiency. By contrast, our ELISA and qRT-PCR analyses demonstrated that PiT-2 mRNA and protein levels vary with gestational age, correlating with the observed differences in transduction efficiency.
Conclusions The findings of the present study explain the age-related differences that we previously observed in transduction efficiency after in utero GT. They also suggest it may be possible to achieve relatively selective GT to specific tissues by performing in utero GT when levels of PiT-2 are maximal in the desired target organ. Copyright (C) 2012 John Wiley & Sons, Ltd.
C1 [Ozturk, Ferhat; Park, Paul J.; Tellez, Joseph; Colletti, Evan; Almeida-Porada, Graca; Porada, Christopher D.] Univ Nevada, Dept Anim Biotechnol, Reno, NV 89557 USA.
[Eiden, Maribeth V.] NIMH, Sect Mol Virol, LCMR, Bethesda, MD 20892 USA.
RP Porada, CD (reprint author), Wake Forest Inst Regenerat Med, Richard H Dean Biomed Bldg,4th Floor,391 Tecnol W, Winston Salem, NC 27157 USA.
EM cporada@wfubmc.edu
RI Ozturk, Ferhat/F-9983-2013
OI Ozturk, Ferhat/0000-0003-3066-1638
FU National Institutes of Health [HD43038]
FX This work was supported by grant #HD43038 from the National Institutes
of Health.
NR 22
TC 1
Z9 1
U1 0
U2 7
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1099-498X
J9 J GENE MED
JI J. Gene. Med.
PD MAR
PY 2012
VL 14
IS 3
BP 169
EP 181
DI 10.1002/jgm.2607
PG 13
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 911IL
UT WOS:000301710400005
PM 22262359
ER
PT J
AU Lohith, TG
Zoghbi, SS
Morse, CL
Araneta, MF
Barth, VN
Goebl, NA
Tauscher, JT
Pike, VW
Innis, RB
Fujita, M
AF Lohith, Talakad G.
Zoghbi, Sami S.
Morse, Cheryl L.
Araneta, Maria F.
Barth, Vanessa N.
Goebl, Nancy A.
Tauscher, Johannes T.
Pike, Victor W.
Innis, Robert B.
Fujita, Masahiro
TI Brain and Whole-Body Imaging of Nociceptin/Orphanin FQ Peptide Receptor
in Humans Using the PET Ligand C-11-NOP-1A
SO JOURNAL OF NUCLEAR MEDICINE
LA English
DT Article
DE NOP receptors; nociceptin; opioid receptor; PET; receptor imaging
ID POSITRON-EMISSION-TOMOGRAPHY; ALCOHOL-DRINKING; MESSENGER-RNA;
RADIOLIGAND; BINDING; AGONIST; ACTIVATION; EXPRESSION; ORL1
AB Nociceptin/orphanin FQ peptide (NOP) receptor is a new class of opioid receptor that may play a pathophysiologic role in anxiety and drug abuse and is a potential therapeutic target in these disorders. We previously developed a high-affinity PET ligand, C-11-NOP-1A, which yielded promising results in monkey brain. Here, we assessed the ability of C-11-NOP-1A to quantify NOP receptors in human brain and estimated its radiation safety profile. Methods: After intravenous injection of C-11-NOP-1A, 7 healthy subjects underwent brain PET for 2 h and serial sampling of radial arterial blood to measure parent radioligand concentrations. Distribution volume (V-T; a measure of receptor density) was determined by compartmental (1- and 2-tissue) and noncompartmental (Logan analysis and Ichise's bilinear analysis [MA1]) methods. A separate group of 9 healthy subjects underwent whole-body PET to estimate whole-body radiation exposure (effective dose). Results: After 11C-NOP-1A injection, the peak concentration of radioactivity in brain was high (similar to 5-7 standardized uptake values), occurred early (similar to 10 min), and then washed out quickly. The unconstrained 2-tissue-compartment model gave excellent V-T identifiability (similar to 1.1% SE) and fitted the data better than a 1-tissue-compartment model. Regional V-T values (mL.cm(-3)) ranged from 10.1 in temporal cortex to 5.6 in cerebellum. VT was well identified in the initial 70 min of imaging and remained stable for the remaining 50 min, suggesting that brain radioactivity was most likely parent radioligand, as supported by the fact that all plasma radiometabolites of C-11-NOP-1A were less lipophilic than the parent radioligand. Voxel-based MA1 V-T values correlated well with results from the 2-tissue-compartment model, showing that parametric methods can be used to compare populations. Whole-body scans showed radioactivity in brain and in peripheral organs expressing NOP receptors, such as heart, pancreas, and spleen. C-11-NOP-1A was significantly metabolized and excreted via the hepatobiliary route. Gallbladder had the highest radiation exposure (21 mu Sv/MBq), and the effective dose was 4.3 mu Sv/MBq. Conclusion: C-11-NOP-1A is a promising radioligand that reliably quantifies NOP receptors in human brain. The effective dose in humans is low and similar to that of other C-11-labeled radioligands, allowing multiple scans in 1 subject.
C1 [Lohith, Talakad G.; Zoghbi, Sami S.; Morse, Cheryl L.; Araneta, Maria F.; Pike, Victor W.; Innis, Robert B.; Fujita, Masahiro] NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA.
[Barth, Vanessa N.; Goebl, Nancy A.; Tauscher, Johannes T.] Eli Lilly & Co, Indianapolis, IN 46285 USA.
RP Innis, RB (reprint author), NIMH, Mol Imaging Branch, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA.
EM robert.innis@nih.gov
RI Tauscher, Johannes/M-5976-2016
FU National Institute of Mental Health, National Institutes of Health
(IRP-NIMH-NIH); Cooperative Research and Development Agreement; Eli
Lilly Co.
FX This study was supported by the Intramural Research Program of the
National Institute of Mental Health, National Institutes of Health
(IRP-NIMH-NIH), and by a Cooperative Research and Development Agreement
with Eli Lilly & Co. We thank Denise Rallis-Frutos, Gerald L. Hodges,
Kimberly Jenko, David Clark, Jeih-San Liow, Robert L. Gladding, and the
staff of the PET Department for assistance in successful completion of
the studies, and PMOD Technologies (Zurich, Switzerland) for providing
its image analysis and modeling software. Ioline Henter provided
invaluable editorial assistance. No other potential conflict of interest
relevant to this article was reported.
NR 26
TC 21
Z9 21
U1 1
U2 7
PU SOC NUCLEAR MEDICINE INC
PI RESTON
PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA
SN 0161-5505
J9 J NUCL MED
JI J. Nucl. Med.
PD MAR 1
PY 2012
VL 53
IS 3
BP 385
EP 392
DI 10.2967/jnumed.111.097162
PG 8
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 904KL
UT WOS:000301194300034
PM 22312136
ER
PT J
AU Coleman, CN
Lurie, N
AF Coleman, C. Norman
Lurie, Nicole
TI Emergency medical preparedness for radiological/nuclear incidents in the
United States
SO JOURNAL OF RADIOLOGICAL PROTECTION
LA English
DT Article
AB The Office of the Assistant Secretary for Preparedness and Response in the Department of Health and Human Services develops health and medical response plans for all hazards-natural and human caused. While a nuclear power plant (NPP) incident will take time to evolve, a terrorist incident will have 'no-notice' so that extensive preparation and planning are essential. For radiological/nuclear (rad/nuc) incidents we have developed and continue to refine detailed plans and tools for medical responders for a nuclear detonation and a radiological dispersal device, which also serve for any type of rad/nuc incident. The plans are based on the best available basic science with the goal of providing planners and responders with just-in-time information and tools. There is much in common across the range of hazards, so that the products developed for rad/nuc incidents have helped overall preparedness. A major consideration in the development of new diagnostics, medical treatment and countermeasures for radiation injury is that of 'dual utility' with potential for routine medical use for cancer care. Participation and collaboration among nations helping the Japanese response to the Fukushima earthquake, tsunami and NPP disaster demonstrated the benefit of preparation and ongoing worldwide cooperation among experts.
C1 [Coleman, C. Norman] NCI, Off Assistant Secretary Preparedness & Response A, Washington, DC USA.
NCI, DHHS, Washington, DC USA.
RP Coleman, CN (reprint author), NCI, Off Assistant Secretary Preparedness & Response A, Washington, DC USA.
EM ccoleman@mail.nih.gov
NR 16
TC 2
Z9 2
U1 0
U2 4
PU IOP PUBLISHING LTD
PI BRISTOL
PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND
SN 0952-4746
J9 J RADIOL PROT
JI J. Radiol. Prot.
PD MAR
PY 2012
VL 32
IS 1
BP N27
EP N32
DI 10.1088/0952-4746/32/1/N27
PG 6
WC Environmental Sciences; Public, Environmental & Occupational Health;
Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical
Imaging
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Nuclear Science & Technology; Radiology, Nuclear Medicine &
Medical Imaging
GA 906ND
UT WOS:000301351200009
PM 22395159
ER
PT J
AU Tronko, M
Mabuchi, K
Bogdanova, T
Hatch, M
Likhtarev, I
Bouville, A
Oliynik, V
McConnell, R
Shpak, V
Zablotska, L
Tereshchenko, V
Brenner, A
Zamotayeva, G
AF Tronko, Mykola
Mabuchi, Kiyohiko
Bogdanova, Tetiana
Hatch, Maureen
Likhtarev, Ilya
Bouville, Andre
Oliynik, Valeriy
McConnell, Robert
Shpak, Viktor
Zablotska, Lydia
Tereshchenko, Valeriy
Brenner, Alina
Zamotayeva, Galyna
TI Thyroid cancer in Ukraine after the Chernobyl accident (in the framework
of the Ukraine-US Thyroid Project)
SO JOURNAL OF RADIOLOGICAL PROTECTION
LA English
DT Article
ID DISEASES; COHORT
AB As a result of the accident at the Chernobyl Nuclear Power Plant, millions of residents of Belarus, Russia, and Ukraine were exposed to large doses of radioactive iodine isotopes, mainly I-131. The purpose of the Ukraine-American (UkrAm) and Belarus-American (BelAm) projects are to quantify the risks of thyroid cancer in the framework of a classical cohort study, comprising subjects who were aged under 18 years at the time of the accident, had direct measurements of thyroid I-131 radioactivity taken within two months after the accident, and were residents of three heavily contaminated northern regions of Ukraine (Zhitomir, Kiev, and Chernigov regions). Four two-year screening examination cycles were implemented from 1998 until 2007 to study the risks associated with thyroid cancer due to the iodine exposure caused during the Chernobyl accident. A standardised procedure of clinical examinations included: thyroid palpation, ultrasound examination, blood collection followed by a determination of thyroid hormone levels, urinary iodine content test, and fine-needle aspiration if required. Among the 110 cases of thyroid cancer diagnosed in UkrAm as the result of four screening examinations, 104 cases (94.5%) of papillary carcinomas, five cases (4.6%) of follicular carcinomas, and one case (0.9%) of medullary carcinoma were diagnosed.
C1 [Tronko, Mykola; Bogdanova, Tetiana; Oliynik, Valeriy; Shpak, Viktor; Tereshchenko, Valeriy; Zamotayeva, Galyna] Ukraine Acad Med Sci, State Inst, VP Komisarenko Inst Endocrinol & Metab, UA-04114 Kiev, Ukraine.
[Mabuchi, Kiyohiko; Hatch, Maureen; Bouville, Andre; Brenner, Alina] Natl Canc Inst USA, Div Canc Epidemiol & Genet, Radiat Epidemiol Branch, Rockville, MD USA.
[Likhtarev, Ilya] Natl Acad Med Sci Ukraine, Res Ctr Radiat Med, Kiev, Ukraine.
[McConnell, Robert] Columbia Univ, Coll Phys & Surg, Thyroid Clin, Dept Med, New York, NY USA.
[Zablotska, Lydia] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco Sch Med, San Francisco, CA 94143 USA.
RP Tronko, M (reprint author), Ukraine Acad Med Sci, State Inst, VP Komisarenko Inst Endocrinol & Metab, Vyshgorodska 69, UA-04114 Kiev, Ukraine.
EM m.tronko@dccie.kiev.ua
FU Intramural NIH HHS [ZIA CP010132-18]
NR 9
TC 6
Z9 6
U1 1
U2 7
PU IOP PUBLISHING LTD
PI BRISTOL
PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND
SN 0952-4746
J9 J RADIOL PROT
JI J. Radiol. Prot.
PD MAR
PY 2012
VL 32
IS 1
BP N65
EP N69
DI 10.1088/0952-4746/32/1/N65
PG 5
WC Environmental Sciences; Public, Environmental & Occupational Health;
Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical
Imaging
SC Environmental Sciences & Ecology; Public, Environmental & Occupational
Health; Nuclear Science & Technology; Radiology, Nuclear Medicine &
Medical Imaging
GA 906ND
UT WOS:000301351200016
PM 22394669
ER
PT J
AU Ayres, EJ
Hoggle, LB
AF Ayres, Elaine J.
Hoggle, Lindsey B.
TI 2011 Nutrition Informatics Member Survey
SO JOURNAL OF THE ACADEMY OF NUTRITION AND DIETETICS
LA English
DT Article
C1 [Ayres, Elaine J.] NIH, Lab Informat Dev, Ctr Clin, Bethesda, MD 20892 USA.
[Hoggle, Lindsey B.] Acad Nutr & Dietet, Washington, DC USA.
RP Ayres, EJ (reprint author), NIH, Lab Informat Dev, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA.
FU Laboratory for Informatics Development, NIH Clinical Center, National
Institutes of Health
FX This work was supported by the Laboratory for Informatics Development,
NIH Clinical Center, National Institutes of Health. The 2010-2011
Nutrition Informatics Committee: Martin Yadrick, MBA, MS, RD, FADA;
Margaret Dittloff, MS, RD; Nancy Collins, PhD, RD, LDN; Phyllis McShane,
MS, RD, LDN; and Amy Miller, RD, provided excellent assistance with
content and testing. Academy staff support was provided by Diane
Juskelis, MS, RD, LDN, and Harold Holler, RD, LDN. The HIMSS Analytics
collaborator was Jennifer Horowitz.
NR 3
TC 6
Z9 6
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 2212-2672
J9 J ACAD NUTR DIET
JI J. Acad. Nutr. Diet.
PD MAR
PY 2012
VL 112
IS 3
BP 360
EP +
DI 10.1016/j.jand.2012.01.003
PG 5
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 905VU
UT WOS:000301305100003
PM 22709663
ER
PT J
AU Habbema, D
de Kok, IMCM
Brown, ML
AF Habbema, Dik
de Kok, Inge M. C. M.
Brown, Martin L.
TI Cervical Cancer Screening in the United States and the Netherlands: A
Tale of Two Countries
SO MILBANK QUARTERLY
LA English
DT Article
DE Cancer; screening; pap testing; comparative effectiveness; clinical
guidelines; cross-country study; preventive services; health care
policy; economic efficiency
ID EARLY-DETECTION PROGRAM; HUMAN-PAPILLOMAVIRUS; COST-EFFECTIVENESS;
NATIONAL BREAST; HEALTH; WOMEN; RISK; PAP; US; PREVALENCE
AB Context: This article compares cervical cancer screening intensity and cervical cancer mortality trends in the United States and the Netherlands to illustrate the potential of cross-national comparative studies. We discuss the lessons that can be learned from the comparison as well as the challenges in each country to effective and efficient screening.
Methods: We used nationally representative data sources in the United States and the Netherlands to estimate the number of Pap smears and the cervical cancer mortality rate since 1950. The following questions are addressed: How do differences in intensity of Pap smear use between the countries translate into differences in mortality trends? Can population coverage rates ( the proportion of eligible women who had a Pap smear within a specified period) explain the mortality trends better than the total intensity of Pap smear use?
Findings: Even though three to four times more Pap smears per woman were conducted in the United States than in the Netherlands over a period of three decades, the two countries' mortality trends were quite similar. The five-year coverage rates for women aged thirty to sixty-four were quite comparable at 80 to 90 percent. Because screening in the Netherlands was limited to ages thirty to sixty, screening rates for women under thirty and over sixty were much higher in the United States. These differences had consequences for age-specific mortality trends. The relatively good coverage rate in the Netherlands can be traced back to a nationwide invitation system based on municipal population registries. While both countries followed a "policy cycle" involving evidence review, surveillance of screening practices and outcomes, clinical guidelines, and reimbursement policies, the components of this cycle were more systematically linked and implemented nationwide in the Netherlands than in the United States. To a large extent, this was facilitated by a public health model of screening in the Netherlands, rather than a medical services model.
Conclusions: Cross-country studies like ours are natural experiments that can produce insights not easily obtained from other types of study. The cervical cancer screening system in the Netherlands seems to have been as effective as the U. S. system but used much less screening. Adequate coverage of the female population at risk seems to be of central importance.
C1 [Brown, Martin L.] NCI, Hlth Serv & Econ Branch, Bethesda, MD 20892 USA.
[Habbema, Dik; de Kok, Inge M. C. M.] Erasmus MC Univ, Med Ctr, Rotterdam, Netherlands.
RP Brown, ML (reprint author), NCI, Hlth Serv & Econ Branch, 6130 Execut Blvd,EPN 4005, Bethesda, MD 20892 USA.
EM mb53o@nih.gov
NR 74
TC 32
Z9 32
U1 0
U2 5
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0887-378X
J9 MILBANK Q
JI Milbank Q.
PD MAR
PY 2012
VL 90
IS 1
BP 5
EP 37
DI 10.1111/j.1468-0009.2011.00652.x
PG 33
WC Health Care Sciences & Services; Health Policy & Services
SC Health Care Sciences & Services
GA 910OO
UT WOS:000301649300002
PM 22428690
ER
PT J
AU Kelly, RJ
Sharon, E
Pastan, I
Hassan, R
AF Kelly, Ronan J.
Sharon, Elad
Pastan, Ira
Hassan, Raffit
TI Mesothelin-Targeted Agents in Clinical Trials and in Preclinical
Development
SO MOLECULAR CANCER THERAPEUTICS
LA English
DT Review
ID MONOCLONAL-ANTIBODY MORAB-009; PANCREATIC-CANCER; OVARIAN-CANCER;
ANTITUMOR-ACTIVITY; IMMUNOTOXIN SS1P; IN-VITRO; T-CELLS; PHASE-I;
RECOMBINANT IMMUNOTOXIN; TUMOR XENOGRAFTS
AB Mesothelin is a tumor differentiation antigen that is highly expressed in several malignant diseases in humans, including malignant mesothelioma and pancreatic, ovarian, and lung adenocarcinomas. The limited expression of mesothelin on normal human tissues and its high expression in many common cancers make it an attractive candidate for cancer therapy. Several agents, including an immunotoxin, monoclonal antibody, antibody drug conjugate, and tumor vaccine, are in various stages of development to treat patients with mesothelin-expressing tumors. This review highlights ongoing clinical trials, as well as other approaches to exploit mesothelin for cancer therapy, that are in preclinical development. Mol Cancer Ther; 11(3); 517-25. (C) 2012 AACR.
C1 [Pastan, Ira; Hassan, Raffit] NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Kelly, Ronan J.; Sharon, Elad] NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA.
RP Hassan, R (reprint author), NCI, Mol Biol Lab, Ctr Canc Res, NIH, 37 Convent Dr,Rm 5116, Bethesda, MD 20892 USA.
EM hassanr@mail.nih.gov
FU Center for Cancer Research, National Cancer Institute, National
Institutes of Health
FX Intramural Research Program of the Center for Cancer Research, National
Cancer Institute, National Institutes of Health.
NR 56
TC 49
Z9 50
U1 3
U2 16
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1535-7163
J9 MOL CANCER THER
JI Mol. Cancer Ther.
PD MAR
PY 2012
VL 11
IS 3
BP 517
EP 525
DI 10.1158/1535-7163.MCT-11-0454
PG 9
WC Oncology
SC Oncology
GA 904WL
UT WOS:000301229500001
PM 22351743
ER
PT J
AU Yong, KJ
Milenic, DE
Baidoo, KE
Brechbiel, MW
AF Yong, Kwon Joong
Milenic, Diane E.
Baidoo, Kwamena E.
Brechbiel, Martin W.
TI Pb-212-Radioimmunotherapy Induces G(2) Cell-Cycle Arrest and Delays DNA
Damage Repair in Tumor Xenografts in a Model for Disseminated
Intraperitoneal Disease
SO MOLECULAR CANCER THERAPEUTICS
LA English
DT Article
ID ALPHA-PARTICLE RADIOIMMUNOTHERAPY; DISSEMINATED PERITONEAL DISEASE;
CANCER CELLS; IN-VITRO; IONIZING-RADIATION; CLINICAL-TRIALS; TARGETING
HER2; APOPTOSIS; INDUCTION; TRASTUZUMAB
AB In preclinical studies, targeted radioimmunotherapy using (212)pb-TCMC-trastuzumab as an in vivo generator of the high-energy a-particle emitting radionuclide Bi-212 is proving an efficacious modality for the treatment of disseminated peritoneal cancers. To elucidate mechanisms associated with this therapy, mice bearing human colon cancer LS-174T intraperitoneal xenografts were treated with (212)pb-TCMC-trastuzumab and compared with the nonspecific control (212)pb-TCMC-HuIgG, unlabeled trastuzumab, and HuIgG, as well as untreated controls. (212)pb-TCMC-trastuzumab treatment induced significantly more apoptosis and DNA double-strand breaks (DSB) at 24 hours. Rad51 protein expression was downregulated, indicating delayed DNA double-strand damage repair compared with (212)pb-TCMC-HuIgG, the nonspecific control. (212)pb-TCMC-trastuzumab treatment also caused G2-M arrest, depression of the S phase fraction, and depressed DNA synthesis that persisted beyond 120 hours. In contrast, the effects produced by (212)pb-TCMC-HuIgG seemed to rebound by 120 hours. In addition, (212)pb-TCMC-trastuzumab treatment delayed open chromatin structure and expression of p21 until 72 hours, suggesting a correlation between induction of p21 protein and modification in chromatin structure of p21 in response to (212)pb-TCMC-trastuzumab treatment. Taken together, increased DNA DSBs, impaired DNA damage repair, persistent G(2)-M arrest, and chromatin remodeling were associated with (212)pb-TCMC-trastuzumab treatment and may explain its increased cell killing efficacy in the LS-174T intraperitoneal xenograft model for disseminated intraperitoneal disease. Mol Cancer Ther; 11(3); 639-48. (C) 2012 AACR.
C1 [Yong, Kwon Joong; Milenic, Diane E.; Baidoo, Kwamena E.; Brechbiel, Martin W.] NCI, Radioimmune & Inorgan Chem Sect, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA.
RP Brechbiel, MW (reprint author), NCI, Radioimmune & Inorgan Chem Sect, Radiat Oncol Branch, NIH, Bldg 10,Room B3B69,10 Ctr Dr, Bethesda, MD 20892 USA.
EM martinwb@mail.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 48
TC 21
Z9 21
U1 0
U2 2
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1535-7163
J9 MOL CANCER THER
JI Mol. Cancer Ther.
PD MAR
PY 2012
VL 11
IS 3
BP 639
EP 648
DI 10.1158/1535-7163.MCT-11-0671
PG 10
WC Oncology
SC Oncology
GA 904WL
UT WOS:000301229500012
PM 22238365
ER
PT J
AU Chu, C
Hsu, AL
Chou, KH
Bandettini, P
Lin, CP
AF Chu, Carlton
Hsu, Ai-Ling
Chou, Kun-Hsien
Bandettini, Peter
Lin, ChingPo
CA Alzheimer's Dis Neuroimaging
TI Does feature selection improve classification accuracy? Impact of sample
size and feature selection on classification using anatomical magnetic
resonance images
SO NEUROIMAGE
LA English
DT Article
DE Feature selection; Support vector machine (SVM); Diseases
classification; Recursive feature elimination (RFE)
ID MILD COGNITIVE IMPAIRMENT; VOXEL-BASED MORPHOMETRY; SUPPORT VECTOR
MACHINES; FMRI ACTIVITY PATTERNS; ALZHEIMERS-DISEASE; FUNCTIONAL MRI;
MATTER LOSS; PREDICTION; REGRESSION; NETWORKS
AB There are growing numbers of studies using machine learning approaches to characterize patterns of anatomical difference discernible from neuroimaging data. The high-dimensionality of image data often raises a concern that feature selection is needed to obtain optimal accuracy. Among previous studies, mostly using fixed sample sizes, some show greater predictive accuracies with feature selection, whereas others do not. In this study, we compared four common feature selection methods. 1) Pre-selected region of interests (ROIs) that are based on prior knowledge. 2) Univariate t-test filtering. 3) Recursive feature elimination (RFE), and 4) t-test filtering constrained by ROIs. The predictive accuracies achieved from different sample sizes, with and without feature selection, were compared statistically. To demonstrate the effect, we used grey matter segmented from the T1-weighted anatomical scans collected by the Alzheimer's disease Neuroimaging Initiative (ADNI) as the input features to a linear support vector machine classifier. The objective was to characterize the patterns of difference between Alzheimer's disease (AD) patients and cognitively normal subjects, and also to characterize the difference between mild cognitive impairment (MCI) patients and normal subjects. In addition, we also compared the classification accuracies between MCI patients who converted to AD and MCI patients who did not convert within the period of 12 months. Predictive accuracies from two data-driven feature selection methods (t-test filtering and RFE) were no better than those achieved using whole brain data. We showed that we could achieve the most accurate characterizations by using prior knowledge of where to expect neurodegeneration (hippocampus and parahippocampal gyrus). Therefore, feature selection does improve the classification accuracies, but it depends on the method adopted. In general, larger sample sizes yielded higher accuracies with less advantage obtained by using knowledge from the existing literature. (C) 2011 Elsevier Inc. All rights reserved.
C1 [Chou, Kun-Hsien; Lin, ChingPo] Natl Yang Ming Univ, Inst Neurosci, Brain Connect Lab, Taipei 112, Taiwan.
[Chu, Carlton; Bandettini, Peter] NIMH, Sect Funct Imaging Methods, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA.
[Hsu, Ai-Ling; Lin, ChingPo] Natl Yang Ming Univ, Inst Brain Sci, Taipei 112, Taiwan.
RP Lin, CP (reprint author), Natl Yang Ming Univ, Inst Neurosci, Brain Connect Lab, 155 Nong St,Sec 2, Taipei 112, Taiwan.
EM cplin@ym.edu.tw
RI Bandettini, Peter/F-5871-2012; Kowall, Neil/G-6364-2012; Preda, Adrian
/K-8889-2013; Saykin, Andrew/A-1318-2007
OI Kowall, Neil/0000-0002-6624-0213; Preda, Adrian /0000-0003-3373-2438;
Saykin, Andrew/0000-0002-1376-8532
FU NIH; NIMH; National Science Council of Taiwan [NSC
100-2628-E-010-002-MY3, NSC 100-2627-B-010-004-]; National Health
Research Institute [NHRI-EX100-9813EC]; Wellcome Trust; Alzheimer's
Disease Neuroimaging Initiative (ADNI) (National Institutes of Health)
[U01 AG024904]; National Institute on Aging; National Institute of
Biomedical Imaging and Bioengineering (NIBIB)
FX This research was supported in part by the Intramural Research Program
of the NIH, NIMH, National Science Council of Taiwan (NSC
100-2628-E-010-002-MY3, NSC 100-2627-B-010-004-) and National Health
Research Institute (NHRI-EX100-9813EC). JA is funded by the Wellcome
Trust. This study utilized the high performance computational
capabilities of the Biowulf Linux cluster at the National Institutes of
Health, Bethesda, MD (http://biowulf.nih.gov).; Data collection and
sharing for this project was funded by the Alzheimer's Disease
Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01
AG024904). ADNI is funded by the National Institute on Aging, the
National Institute of Biomedical Imaging and Bioengineering (NIBIB), and
through generous contributions from the following: Abbott, AstraZeneca
AB, Bayer Schering Pharma AG, Bristol-Myers Squibb, Eisai Global
Clinical Development, Elan Corporation, Genentech, GE Healthcare,
GlaxoSmithKline, Innogenetics, Johnson and Johnson, Eli Lilly and
Co.,Medpace, Inc.,Merck and Co., Inc., Novartis AG, Pfizer Inc., F.
Hoffman-La Roche, Schering-Plough, Synarc, Inc., as well as non-profit
partners the Alzheimer's Association and Alzheimer's Drug Discovery
Foundation, with participation from the U.S. Food and Drug
Administration. Private sector contributions to ADNI are facilitated by
the Foundation for the National Institutes of Health (www.fnih.org). The
grantee organization is the Northern California Institute for Research
and Education, and the study is coordinated by the Alzheimer's Disease
Cooperative Study at the University of California, San Diego. ADNI data
are disseminated by the Laboratory for Neuro Imaging at the University
of California, Los Angeles.
NR 48
TC 75
Z9 79
U1 5
U2 24
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1053-8119
J9 NEUROIMAGE
JI Neuroimage
PD MAR
PY 2012
VL 60
IS 1
BP 59
EP 70
DI 10.1016/j.neuroimage.2011.11.066
PG 12
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 904SR
UT WOS:000301218700007
PM 22166797
ER
PT J
AU Robinson, OJ
Charney, DR
Overstreet, C
Vytal, K
Grillon, C
AF Robinson, Oliver J.
Charney, Danielle R.
Overstreet, Cassie
Vytal, Katherine
Grillon, Christian
TI The adaptive threat bias in anxiety: Amygdala-dorsomedial prefrontal
cortex coupling and aversive amplification
SO NEUROIMAGE
LA English
DT Article
DE Amygdala; DMPFC; Functional connectivity; Prelimbic; Anxiety; Threat
bias
ID ANTERIOR CINGULATE CORTEX; COGNITIVE CONTROL; CONDITIONED FEAR; HUMANS;
EXTINCTION; MECHANISMS; EXPRESSION; BRAIN; DEPRESSION; ACTIVATION
AB Functionally, anxiety serves to increase vigilance towards aversive stimuli and improve the ability to detect and avoid danger. We have recently shown, for instance, that anxiety increases the ability to a) detect and b) instigate defensive responses towards aversive and not appetitive face stimuli in healthy individuals. This is arguably the key adaptive function of anxiety, yet the neural circuitry underlying this valence-specific effect is unknown. In the present translational study, we sought evidence for the proposition that dorsomedial regions of the prefrontal (DMPFC) and cingulate cortex constitute the human homologue of the rodent prelimbic and are thus associated with increased amygdala responding during this adaptive threat bias in anxiety. To this end, we applied a novel functional connectivity analysis to healthy subjects (N=20) identifying the emotion of fearful and happy faces in an fMRI scanner under anxious (threat of unpredictable foot shock) and non-anxious (safe) conditions. We showed that anxiety significantly increased positive DMPFC-amygdala connectivity during the processing of fearful faces. This effect was a) valence-specific (it was not seen for happy faces), b) paralleled by faster behavioral response to fearful faces, and c) correlated positively with trait anxiety. As such we provide the first experimental support for an anxiety-mediated, valence-specific, DMPFC-amygdala aversive amplification mechanism in healthy humans. This may be homologous to the rodent prelimbic-amygdala circuit and may, given the relationship with trait anxiety, underlie vulnerability to anxiety disorders. This study thus pinpoints a key neural mechanism in adaptive anxiety and highlights its potential link to maladaptive anxiety. Published by Elsevier Inc.
C1 [Robinson, Oliver J.] NIMH, MAP, Sect Neurobiol Fear & Anxiety, NIH, Bethesda, MD 20892 USA.
RP Robinson, OJ (reprint author), NIMH, MAP, Sect Neurobiol Fear & Anxiety, NIH, 15K North Dr,Room 203,MSC 2670, Bethesda, MD 20892 USA.
EM oliver.j.robinson@gmail.com
RI Robinson, Oliver/B-3646-2011
OI Robinson, Oliver/0000-0002-3100-1132
FU National Institutes of Mental Health
FX This research was supported by the Intramural Research Program of the
National Institutes of Mental Health. We would like to thank Angie Wu
and Jeannette Black for the invaluable participation and technical
support and Stephen Fromm for fMRI analysis discussions. This work was
presented in part at the Society for Psychophysiological Research in
Boston, September 2011.
NR 37
TC 59
Z9 61
U1 1
U2 37
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1053-8119
J9 NEUROIMAGE
JI Neuroimage
PD MAR
PY 2012
VL 60
IS 1
BP 523
EP 529
DI 10.1016/j.neuroimage.2011.11.096
PG 7
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 904SR
UT WOS:000301218700053
PM 22178453
ER
PT J
AU Bulte, DP
Kelly, M
Germuska, M
Xie, J
Chappell, MA
Okell, TW
Bright, MG
Jezzard, P
AF Bulte, D. P.
Kelly, M.
Germuska, M.
Xie, J.
Chappell, M. A.
Okell, T. W.
Bright, M. G.
Jezzard, P.
TI Quantitative measurement of cerebral physiology using
respiratory-calibrated MRI
SO NEUROIMAGE
LA English
DT Article
DE FMRI; Hyperoxia; Hypercapnia; CMRO2
ID OXYGEN EXTRACTION FRACTION; SPIN-LABELING MRI;
POSITRON-EMISSION-TOMOGRAPHY; BLOOD-FLOW; BOLD-FMRI; CEREBROVASCULAR
REACTIVITY; OXIDATIVE-METABOLISM; CARBON-DIOXIDE; FUNCTIONAL MRI; HUMAN
BRAIN
AB Functional magnetic resonance imaging typically measures signal increases arising from changes in the transverse relaxation rate over small regions of the brain and associates these with local changes in cerebral blood flow, blood volume and oxygen metabolism. Recent developments in pulse sequences and image analysis methods have improved the specificity of the measurements by focussing on changes in blood flow or changes in blood volume alone. However. FMRI is still unable to match the physiological information obtainable from positron emission tomography (PET), which is capable of quantitative measurements of blood flow and volume, and can indirectly measure resting metabolism. The disadvantages of PET are its cost, its availability, its poor spatial resolution and its use of ionising radiation. The MRI techniques introduced here address some of these limitations and provide physiological data comparable with PET measurements. We present an 18-minute MRI protocol that produces multi-slice whole-brain coverage and yields quantitative images of resting cerebral blood flow, cerebral blood volume, oxygen extraction fraction, CMRO2, arterial arrival time and cerebrovascular reactivity of the human brain in the absence of any specific functional task. The technique uses a combined hyperoxia and hypercapnia paradigm with a modified arterial spin labelling sequence. (C) 2011 Elsevier Inc. All rights reserved.
C1 [Bulte, D. P.; Kelly, M.; Germuska, M.; Xie, J.; Chappell, M. A.; Okell, T. W.; Bright, M. G.; Jezzard, P.] Univ Oxford, FMRIB Ctr, Nuffield Dept Clin Neurosci, Oxford OX3 9DU, England.
[Chappell, M. A.] Univ Oxford, Dept Engn Sci, Inst Biomed Engn, Oxford OX3 9DU, England.
[Bright, M. G.] Natl Inst Neurol Disorders & Stroke, Adv MRI Sect, Lab Funct & Mol Imaging, NIH, Bethesda, MD USA.
[Bright, M. G.] Cardiff Univ, Sch Psychol, Brain Res Imaging Ctr, Cardiff, S Glam, Wales.
RP Bulte, DP (reprint author), Univ Oxford, John Radcliffe Hosp, Nuffield Dept Clin Neurosci, FMRIB Ctr, Oxford OX3 9DU, England.
EM bulte@fmrib.ox.ac.uk
RI Bright, Molly/F-6394-2010;
OI Bright, Molly/0000-0001-7257-9646; Okell, Thomas/0000-0001-8258-0659;
Jezzard, Peter/0000-0001-7912-2251; Chappell,
Michael/0000-0003-1802-4214
FU Engineering and Physical Research Council of the United Kingdom; UK
Medical Research Council; Dunhill Medical Trust; Wellcome Trust; NIHR
Oxford Biomedical Research Centre
FX This research was supported by the Engineering and Physical Research
Council of the United Kingdom, the UK Medical Research Council, the
Dunhill Medical Trust, the Wellcome Trust, and the NIHR Oxford
Biomedical Research Centre.
NR 67
TC 64
Z9 64
U1 2
U2 15
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1053-8119
J9 NEUROIMAGE
JI Neuroimage
PD MAR
PY 2012
VL 60
IS 1
BP 582
EP 591
DI 10.1016/j.neuroimage.2011.12.017
PG 10
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 904SR
UT WOS:000301218700060
PM 22209811
ER
PT J
AU Weise, CM
Thiyyagura, P
Reiman, EM
Chen, KW
Krakoff, J
AF Weise, Christopher M.
Thiyyagura, Pradeep
Reiman, Eric M.
Chen, Kewei
Krakoff, Jonathan
TI Postprandial plasma PYY concentrations are associated with increased
regional gray matter volume and rCBF declines in caudate nuclei - A
combined MRI and (H2O)-O-15 PET study
SO NEUROIMAGE
LA English
DT Article
DE PYY; Caudate nucleus; Striatum; Gray matter; VBM; MRI; PET; rCBF
ID NEUROPEPTIDE-Y; PEPTIDE-YY; FOOD-INTAKE; OBESE SUBJECTS; GUT HORMONE;
RAT-BRAIN; PREFRONTAL CORTEX; RECEPTOR SUBTYPES; DECISION-MAKING;
DOPAMINE
AB The anorexigenic gastrointestinal hormone Peptide YY plays an important role in the communication between the gastrointestinal tract and the central nervous system. PYY has been shown to modulate brain activity in regions implicated in reward and food related behavior. Its effects on brain structure however, remain unknown. Voxel-based morphometry was used to investigate the relationship between fasting and postprandial plasma PYY concentrations and regional gray matter volume (GMV). For this analysis twenty adult, non diabetic Caucasians were included (18 F/2 M, age 31 +/- 9 y, percentage of body fat [PFAT] 32 +/- 8%) who had volumetric brain magnetic resonance images and underwent (H2O)-O-15 positron emission tomographic (PET) measurements of regional cerebral blood flow (rCBF), a marker of local neuronal activity, and measurements of plasma total PYY, prior to (fasting) and following a satiating liquid meal. Voxel-wise analysis revealed a regional positive association between postprandial PYY and gray matter volume bilaterally in the caudate nuclei. These associations remained significant (p<0.05) after small volume correction for multiple comparisons. Based on these findings we investigated whether postprandial PYY is associated with PET measured rCBF of the caudate nucleus. We found a significant negative association between average postprandial caudate rCBF and postprandial plasma PYY concentrations (r = -0.60, p<0.02, age, sex and PFAT adjusted). Average postprandial caudate rCBF was also negatively associated with rCBF in the right medial orbitofrontal cortex and the right hippocampal formation (p<0.05, corrected for multiple comparisons). Total PYY is positively associated with gray matter but negatively with postprandial activity in the caudate nuclei while caudate activity is negatively associated with rCBF in prefrontal and paralimbic regions implicated in reward behavior. Thus, PYY may act centrally to modulate eating behavior via striatal networks. Published by Elsevier Inc.
C1 [Weise, Christopher M.] NIDDK, NIH, PECRB, Obes & Diabet Clin Res Sect,DHHS, Phoenix, AZ 85016 USA.
[Thiyyagura, Pradeep; Reiman, Eric M.; Chen, Kewei] Banner Alzheimers Inst, Dept Psychiat, Phoenix, AZ USA.
[Reiman, Eric M.] Translat Genom Res Inst, Neurogen Div, Phoenix, AZ USA.
RP Weise, CM (reprint author), NIDDK, NIH, PECRB, Obes & Diabet Clin Res Sect,DHHS, 4212 N 16th St, Phoenix, AZ 85016 USA.
EM christopher.weise@nih.gov
RI Chen, kewei/P-6304-2015
OI Chen, kewei/0000-0001-8497-3069
FU Intramural NIH HHS [Z99 DK999999]
NR 68
TC 4
Z9 4
U1 2
U2 7
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1053-8119
J9 NEUROIMAGE
JI Neuroimage
PD MAR
PY 2012
VL 60
IS 1
BP 592
EP 600
DI 10.1016/j.neuroimage.2011.12.023
PG 9
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 904SR
UT WOS:000301218700061
PM 22206963
ER
PT J
AU Chen, G
Saad, ZS
Nath, AR
Beauchamp, MS
Cox, RW
AF Chen, Gang
Saad, Ziad S.
Nath, Audrey R.
Beauchamp, Michael S.
Cox, Robert W.
TI FMRI group analysis combining effect estimates and their variances
SO NEUROIMAGE
LA English
DT Article
DE FMRI group analysis; Effect estimate precision or reliability;
Mixed-effects multilevel analysis (MEMA); Weighted least squares (WLS);
Restricted maximum likelihood (REML); Outliers; AFNI
ID EFFECTS META-REGRESSION; RANDOM-EFFECTS MODEL; METAANALYSIS; INFERENCE;
HETEROGENEITY; TESTS; BIAS
AB Conventional functional magnetic resonance imaging (FMRI) group analysis makes two key assumptions that are not always justified. First, the data from each subject is condensed into a single number per voxel, under the assumption that within-subject variance for the effect of interest is the same across all subjects or is negligible relative to the cross-subject variance. Second, it is assumed that all data values are drawn from the same Gaussian distribution with no outliers. We propose an approach that does not make such strong assumptions, and present a computationally efficient frequentist approach to FMRI group analysis, which we term mixed-effects multilevel analysis (MEMA), that incorporates both the variability across subjects and the precision estimate of each effect of interest from individual subject analyses. On average, the more accurate tests result in higher statistical power, especially when conventional variance assumptions do not hold, or in the presence of outliers. In addition, various heterogeneity measures are available with MEMA that may assist the investigator in further improving the modeling. Our method allows group effect t-tests and comparisons among conditions and among groups. In addition, it has the capability to incorporate subject-specific covariates such as age, IQ or behavioral data. Simulations were performed to illustrate power comparisons and the capability of controlling type I errors among various significance testing methods, and the results indicated that the testing statistic we adopted struck a good balance between power gain and type I error control. Our approach is instantiated in an open-source, freely distributed program that may be used on any dataset stored in the universal neuroimaging file transfer (NIfTI) format. To date, the main impediment for more accurate testing that incorporates both within- and cross-subject variability has been the high computational cost. Our efficient implementation makes this approach practical. We recommend its use in lieu of the less accurate approach in the conventional group analysis. Published by Elsevier Inc.
C1 [Chen, Gang; Saad, Ziad S.; Cox, Robert W.] NIMH, NIH, DHHS, Bethesda, MD 20892 USA.
[Nath, Audrey R.; Beauchamp, Michael S.] Univ Texas Med Sch Houston, Dept Neurobiol & Anat, Houston, TX 77030 USA.
RP Chen, G (reprint author), NIMH, NIH, DHHS, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM gangchen@mail.nih.gov
OI Beauchamp, Michael/0000-0002-7599-9934
FU NIMH; NIH [R01N5065395]; NSF [642532]
FX We are indebted to Wolfgang Viechtbauer for theoretical consultation and
programming support, to Xiang-Gui Qu for the help in mathematical
derivation, to Rick Reynolds for assisting in data analysis, and to
anonymous reviewers for simulation suggestions. Writing of this paper
was supported by the NIMH and NINDS Intramural Research Programs of the
NIH. This research was also supported by NSF 642532 and NIH R01N5065395
to MSB.
NR 40
TC 50
Z9 50
U1 2
U2 15
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1053-8119
J9 NEUROIMAGE
JI Neuroimage
PD MAR
PY 2012
VL 60
IS 1
BP 747
EP 765
DI 10.1016/j.neuroimage.2011.12.060
PG 19
WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical
Imaging
SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging
GA 904SR
UT WOS:000301218700076
PM 22245637
ER
PT J
AU Ross, OA
Singleton, AB
AF Ross, Owen A.
Singleton, Andrew B.
TI Does trans size matter in Huntington disease?
SO NEUROLOGY
LA English
DT Editorial Material
ID REPEAT; ONSET; AGE
C1 [Ross, Owen A.] Mayo Clin, Dept Neurosci, Jacksonville, FL 32224 USA.
[Singleton, Andrew B.] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
RP Ross, OA (reprint author), Mayo Clin, Dept Neurosci, Jacksonville, FL 32224 USA.
EM ross.owen@mayo.edu
RI Singleton, Andrew/C-3010-2009; Ross, Owen/D-7573-2013
FU NIA NIH HHS [Z01 AG000957-09]; NINDS NIH HHS [1RC2NS070276, P50
NS072187]
NR 7
TC 0
Z9 0
U1 1
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0028-3878
J9 NEUROLOGY
JI Neurology
PD MAR
PY 2012
VL 78
IS 10
BP 686
EP 687
DI 10.1212/WNL.0b013e3182494d77
PG 2
WC Clinical Neurology
SC Neurosciences & Neurology
GA 904YR
UT WOS:000301236400002
PM 22323751
ER
PT J
AU Bandmann, O
Cookson, MR
AF Bandmann, Oliver
Cookson, Mark R.
TI Parkinson disease, cancer, and LRRK2 Causation or association?
SO NEUROLOGY
LA English
DT Editorial Material
ID MUTATIONS
C1 [Bandmann, Oliver] Univ Sheffield, SITraN, Dept Neurosci, Sheffield, S Yorkshire, England.
[Cookson, Mark R.] NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
RP Bandmann, O (reprint author), Univ Sheffield, SITraN, Dept Neurosci, Sheffield, S Yorkshire, England.
EM o.bandmann@sheffield.ac.uk
FU Parkinson's UK [G-1007, G-1202, G-0715]
NR 11
TC 6
Z9 6
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0028-3878
J9 NEUROLOGY
JI Neurology
PD MAR
PY 2012
VL 78
IS 11
BP 772
EP 773
DI 10.1212/WNL.0b013e318249f744
PG 2
WC Clinical Neurology
SC Neurosciences & Neurology
GA 907VW
UT WOS:000301448300003
PM 22323745
ER
PT J
AU Chanyshev, B
Shainberg, A
Isak, A
Litinsky, A
Chepurko, Y
Tosh, DK
Phan, K
Gao, ZG
Hochhauser, E
Jacobson, KA
AF Chanyshev, Bella
Shainberg, Asher
Isak, Ahuva
Litinsky, Alexandra
Chepurko, Yelena
Tosh, Dilip K.
Khai Phan
Gao, Zhan-Guo
Hochhauser, Edith
Jacobson, Kenneth A.
TI Anti-ischemic effects of multivalent dendrimeric A(3) adenosine receptor
agonists in cultured cardiomyocytes and in the isolated rat heart
SO PHARMACOLOGICAL RESEARCH
LA English
DT Article
DE Dendrimer; Cardiomyocyte; Adenosine receptor; Ischemia; Isolated heart;
Rat
ID ISCHEMIA/REPERFUSION INJURY; MYOCARDIAL INFARCT; CARDIAC MYOCYTES; CLICK
CHEMISTRY; SIZE; CARDIOPROTECTION; ACTIVATION; PROTECTS; A(1); RESPONSES
AB Adenosine released during myocardial ischemia mediates cardioprotective preconditioning. Multivalent drugs covalently bound to nanocarriers may differ greatly in chemical and biological properties from the corresponding monomeric agents. Here, we conjugated chemically functionalized nucleosides to poly(amidoamine) (PAMAM) dendrimeric polymers and investigated their effects in rat primary cardiac cell cultures and in the isolated heart. Three conjugates of A(3) adenosine receptor (AR) agonists, chain-functionalized at the C2 or N-6 position, were cardioprotective, with greater potency than monomeric agonist Cl-IB-MECA. Multivalent amide-linked MRS5216 was selective for A(1) and A(3)ARs, and triazole-linked MR55246 and MRS5539 (optionally containing fluorescent label) were A(3)AR-selective. The conjugates protected ischemic rat cardiomyocytes, an effect blocked by an A(3)AR antagonist MRS1523, and isolated hearts with significantly improved infarct size, rate of pressure product, and rate of contraction and relaxation. Thus, strategically derivatized nucleosides tethered to biocompatible polymeric carriers display enhanced cardioprotective potency via activation of A(3)AR on the cardiomyocyte surface. Published by Elsevier Ltd.
C1 [Tosh, Dilip K.; Khai Phan; Gao, Zhan-Guo; Jacobson, Kenneth A.] NIDDK, Mol Recognit Sect, LBC, NIH, Bethesda, MD 20892 USA.
[Chanyshev, Bella; Shainberg, Asher; Isak, Ahuva; Litinsky, Alexandra] Bar Ilan Univ, Mina & Everard Goodman Fac Life Sci, Ramat Gan, Israel.
[Chepurko, Yelena; Hochhauser, Edith] Tel Aviv Univ, Dept Cardiothorac Surg, Rabin Med Ctr, Felsenstein Med Res Ctr,Cardiac Res Lab, Petah Tiqwa, Israel.
RP Jacobson, KA (reprint author), NIDDK, Mol Recognit Sect, LBC, NIH, Bldg 8A,Rm B1A-19, Bethesda, MD 20892 USA.
EM kajacobs@helix.nih.gov
RI Jacobson, Kenneth/A-1530-2009
OI Jacobson, Kenneth/0000-0001-8104-1493
FU NIH, NIDDK; Adar Program for the Advancement of Research in Heart
Function; Horowitz Foundation at Bar-Ilan University
FX This research was supported by the Intramural Research Program of the
NIH, NIDDK. This work was also in part supported by The Adar Program for
the Advancement of Research in Heart Function and the Horowitz
Foundation at Bar-Ilan University.
NR 43
TC 8
Z9 9
U1 0
U2 10
PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
PI LONDON
PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
SN 1043-6618
J9 PHARMACOL RES
JI Pharmacol. Res.
PD MAR
PY 2012
VL 65
IS 3
BP 338
EP 346
DI 10.1016/j.phrs.2011.11.013
PG 9
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 909II
UT WOS:000301557800009
PM 22154845
ER
PT J
AU Wen, R
Tao, W
Li, YW
Sieving, PA
AF Wen, Rong
Tao, Weng
Li, Yiwen
Sieving, Paul A.
TI CNTF and retina
SO PROGRESS IN RETINAL AND EYE RESEARCH
LA English
DT Article
DE CNTF; Photoreceptors; Retinal ganglion cells; Retinal degeneration;
Neuroprotection; Photoreceptor plasticity
ID CILIARY NEUROTROPHIC FACTOR; LEUKEMIA INHIBITORY FACTOR;
AMYOTROPHIC-LATERAL-SCLEROSIS; ACUTE-PHASE RESPONSE; CHOLINERGIC
NEURONOTROPHIC FACTORS; LENTIVIRAL-MEDIATED TRANSFER; RHODOPSIN MUTATION
S334TER; CELL INTRAOCULAR IMPLANTS; PERIPHERAL-NERVE GRAFTS; IL-6 SIGNAL
TRANSDUCER
AB Ciliary neurotrophic factor (CNTF) is one of the most studied neurotrophic factors for neuroprotection of the retina. A large body of evidence demonstrates that CNTF promotes rod photoreceptor survival in almost all animal models. Recent studies indicate that CNTF also promotes cone photoreceptor survival and cone outer segment regeneration in the degenerating retina and improves cone function in dogs with congenital achromotopsia. In addition, CNTF is a neuroprotective factor and an axogenesis factor for retinal ganglion cells (RGCs). This review focuses on the effects of exogenous CNTF on photoreceptors and RGCs in the mammalian retina and the potential clinical application of CNTF for retinal degenerative diseases. (C) 2011 Elsevier Ltd. All rights reserved.
C1 [Wen, Rong; Li, Yiwen] Univ Miami, Miller Sch Med, Bascom Palmer Eye Inst, Miami, FL 33136 USA.
[Tao, Weng] Neurotech USA, Lincoln, RI 02865 USA.
[Sieving, Paul A.] NEI, NIH, Bethesda, MD 20892 USA.
RP Wen, R (reprint author), Univ Miami, Miller Sch Med, Bascom Palmer Eye Inst, McKnight Bldg,RM 506,1638 NW 10th Ave, Miami, FL 33136 USA.
EM rwen@med.miami.edu
FU National Institutes of Health [R01EY12727, R01EY018586, P30EY14801];
Hope for Vision; State of Florida; Department of Defense
[W81XWH-09-1-0674]; Research to Prevent Blindness; National Institutes
of Health, National Eye Institute, and National Institute on Deafness
and Other Communication Disorders
FX We thank Dr. Andras Komaromy for allowing us to discuss his unpublished
data and for critically reading the manuscript; and Dr. Byron Lam for
critically reading the manuscript. This work was supported by grants
from National Institutes of Health (R01EY12727, R01EY018586 to RW,
P30EY14801 to Bascom Palmer Eye Institute), Hope for Vision (RW), the
James and Esther King Biomedical Research Program of the State of
Florida (YL), the Department of Defense (W81XWH-09-1-0674 to RW), an
unrestricted grant from Research to Prevent Blindness to Bascom Palmer
Eye Institute; and by the intramural research program of National
Institutes of Health, National Eye Institute, and National Institute on
Deafness and Other Communication Disorders.
NR 145
TC 69
Z9 72
U1 0
U2 17
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 MAR
PY 2012
VL 31
IS 2
BP 136
EP 151
DI 10.1016/j.preteyeres.2011.11.005
PG 16
WC Ophthalmology
SC Ophthalmology
GA 910GC
UT WOS:000301624200002
PM 22182585
ER
PT J
AU Tie, YF
Wang, YF
Boross, PI
Chiu, TY
Ghosh, AK
Tozser, J
Louis, JM
Harrison, RW
Weber, IT
AF Tie, Yunfeng
Wang, Yuan-Fang
Boross, Peter I.
Chiu, Ting-Yi
Ghosh, Arun K.
Tozser, Jozsef
Louis, John M.
Harrison, Robert W.
Weber, Irene T.
TI Critical differences in HIV-1 and HIV-2 protease specificity for
clinical inhibitors
SO PROTEIN SCIENCE
LA English
DT Article
DE HIV; AIDS; drug resistance; aspartic protease; antiviral inhibitors;
molecular recognition
ID RESOLUTION CRYSTAL-STRUCTURES; IMMUNODEFICIENCY-VIRUS PROTEASE;
AMINO-ACID PREFERENCES; DRUG-RESISTANT MUTANTS; RETROVIRAL PROTEASES;
LIGAND SPECIFICITY; CLEAVAGE SITES; SUSCEPTIBILITY; PROTEINASES;
COMPLEXES
AB Clinical inhibitor amprenavir (APV) is less effective on HIV-2 protease (PR2) than on HIV-1 protease (PR1). We solved the crystal structure of PR2 with APV at 1.5 angstrom resolution to identify structural changes associated with the lowered inhibition. Furthermore, we analyzed the PR1 mutant (PR1M) with substitutions V32I, I47V, and V82I that mimic the inhibitor binding site of PR2. PR1M more closely resembled PR2 than PR1 in catalytic efficiency on four substrate peptides and inhibition by APV, whereas few differences were seen for two other substrates and inhibition by saquinavir (SQV) and darunavir (DRV). High resolution crystal structures of PR1M with APV, DRV, and SQV were compared with available PR1 and PR2 complexes. Val/Ile32 and Ile/Val47 showed compensating interactions with SQV in PR1M and PR1, however, Ile82 interacted with a second SQV bound in an extension of the active site cavity of PR1M. Residues 32 and 82 maintained similar interactions with DRV and APV in all the enzymes, whereas Val47 and Ile47 had opposing effects in the two subunits. Significantly diminished interactions were seen for the aniline of APV bound in PR1M and PR2 relative to the strong hydrogen bonds observed in PR1, consistent with 15- and 19-fold weaker inhibition, respectively. Overall, PR1M partially replicates the specificity of PR2 and gives insight into drug resistant mutations at residues 32, 47, and 82. Moreover, this analysis provides a structural explanation for the weaker antiviral effects of APV on HIV-2.
C1 [Tie, Yunfeng; Wang, Yuan-Fang; Chiu, Ting-Yi; Harrison, Robert W.; Weber, Irene T.] Georgia State Univ, Dept Biol, Atlanta, GA 30303 USA.
[Boross, Peter I.; Tozser, Jozsef] Univ Debrecen, Fac Med, Dept Biochem & Mol Biol, Debrecen, Hungary.
[Ghosh, Arun K.] Purdue Univ, Dept Chem & Med Chem, W Lafayette, IN 47907 USA.
[Louis, John M.] NIDDK, Chem Phys Lab, NIH, DHHS, Bethesda, MD 20892 USA.
[Harrison, Robert W.] Georgia State Univ, Dept Comp Sci, Atlanta, GA 30303 USA.
[Weber, Irene T.] Georgia State Univ, Dept Chem, Atlanta, GA 30303 USA.
RP Weber, IT (reprint author), Georgia State Univ, Dept Biol, POB 4010, Atlanta, GA 30302 USA.
EM iweber@gsu.edu
RI Tozser, Jozsef/A-7840-2008;
OI Tozser, Jozsef/0000-0003-0274-0056; Tozser, Jozsef/0000-0001-5076-8729
FU Hungarian Science and Research Fund (OTKA) [K68288, K101591]; NIDDK,
National Institutes of Health (NIH); Office of the Director, NIH
[GM062920, GM53386]; US Department of Energy, Office of Science, Office
of Basic Energy Sciences [W-31-109-Eng-38]
FX This research was authored, in whole or in part, by National Institutes
of Health staff. This research was supported, in whole or in part, by
the Hungarian Science and Research Fund (OTKA K68288, K101591), the
Intramural Research Program of the NIDDK, National Institutes of Health
(NIH), Intramural AIDS-Targeted Antiviral Program of the Office of the
Director, NIH, and grants GM062920 (ITW) and GM53386 (AKG) from the NIH.
The authors thank the staff at the SER-CAT beam-line at the Advanced
Photon Source, Argonne National Laboratory, for assistance during X-ray
data collection. Use of the Advanced Photon Source was supported by the
US Department of Energy, Office of Science, Office of Basic Energy
Sciences, under Contract No. W-31-109-Eng-38.
NR 47
TC 11
Z9 14
U1 0
U2 14
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0961-8368
EI 1469-896X
J9 PROTEIN SCI
JI Protein Sci.
PD MAR
PY 2012
VL 21
IS 3
BP 339
EP 350
DI 10.1002/pro.2019
PG 12
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 895NY
UT WOS:000300504300005
PM 22238126
ER
PT J
AU Scott, TW
Takken, W
AF Scott, Thomas W.
Takken, Willem
TI Feeding strategies of anthropophilic mosquitoes result in increased risk
of pathogen transmission
SO TRENDS IN PARASITOLOGY
LA English
DT Review
DE blood feeding; Anopheles gambiae; malaria; Aedes aegypti; dengue;
mosquito; multiple bloodmeals; sugar; fitness; reproduction; disease
transmission; pathogen transmission
ID AEDES-AEGYPTI DIPTERA; ANOPHELES-GAMBIAE DIPTERA; IDEAL FREE
DISTRIBUTION; SENSU-STRICTO DIPTERA; PUERTO-RICO; HUMAN-BLOOD;
BODY-SIZE; PLASMODIUM-FALCIPARUM; DENGUE VECTOR; DEFENSIVE BEHAVIOR
AB Vector-borne disease specialists have traditionally assumed that in each egg-laying cycle mosquitoes take a single bloodmeal that is used for egg development and feed on plant sugars for flight and production of energy reserves. Here we review research showing that for two of the most important vectors of human pathogens (Anopheles gambiae and Aedes aegypti) imbibing multiple bloodmeals during a gonotrophic cycle while foregoing sugar feeding is a common behaviour, not an exception. By feeding preferentially and frequently on human blood these species increase their fitness and exponentially boost the basic reproduction rate of pathogens they transmit. Although the epidemiological outcome is similar, there are important differences in processes underlying frequent human contact by these species that merit more detailed investigation.
C1 [Scott, Thomas W.] Univ Calif Davis, Dept Entomol, Davis, CA 95616 USA.
[Scott, Thomas W.] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
[Takken, Willem] Wageningen Univ, Entomol Lab, Wageningen, Netherlands.
RP Scott, TW (reprint author), Univ Calif Davis, Dept Entomol, 1 Shields Ave, Davis, CA 95616 USA.
EM twscott@ucdavis.edu; willem.takken@wur.nl
FU Wageningen University
FX We thank L.C. Harrington for helpful discussions and review of an
earlier draft of this manuscript. J.D. Charlwood, C.J.M. Koenraadt,
J.J.A. van Loon, T.A. Perkins and R.C. Reiner are thanked for their
useful comments while developing this paper. Content of this manuscript
benefited from discussions with working group members in the Research
and Policy for Infectious Disease Dynamics (RAPIDD) program of the
Science and Technology Directorate, Department of Homeland Security and
the Fogarty International Centre, National Institutes of Health.
Wageningen University provided financial support for a sabbatical to
W.T., which allowed for collaborative work between the authors. Owing to
space constraints imposed by the journal, we were not able to cite all
the references we would have liked.
NR 76
TC 55
Z9 55
U1 4
U2 51
PU ELSEVIER SCI LTD
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 MAR
PY 2012
VL 28
IS 3
BP 114
EP 121
DI 10.1016/j.pt.2012.01.001
PG 8
WC Parasitology
SC Parasitology
GA 910KK
UT WOS:000301635400006
PM 22300806
ER
PT J
AU Beedie, SA
Benson, PJ
Giegling, I
Rujescu, D
St Clair, DM
AF Beedie, Sara A.
Benson, Philip J.
Giegling, Ina
Rujescu, Dan
St Clair, David M.
TI Smooth pursuit and visual scanpaths: Independence of two candidate
oculomotor risk markers for schizophrenia
SO WORLD JOURNAL OF BIOLOGICAL PSYCHIATRY
LA English
DT Article
DE Schizophrenia; psychosis; genetics; biomarkers; eye movements
ID DORSOLATERAL PREFRONTAL CORTEX; EYE-TRACKING DYSFUNCTION; OCULAR MOTOR
BEHAVIOR; SCAN PATHS; 1ST-DEGREE RELATIVES; MOVEMENT DYSFUNCTION;
1ST-EPISODE SCHIZOPHRENIA; FIELD LESIONS; PERFORMANCE; TRAIT
AB Objectives. Smooth pursuit and visual scanpath deficits are candidate trait markers for schizophrenia. It is not clear whether eye tracking dysfunction (ETD) and atypical scanpath behaviour are the product of the same underlying neurobiological processes. We have examined co-occurrence of ETD and scanpath disturbance in individuals with schizophrenia and healthy volunteers. Methods. Eye movements of individuals with schizophrenia (N = 96) and non-clinical age-matched comparison participants (N = 100) were recorded using non-invasive infrared oculography during smooth pursuit in both predictable (horizontal sinusoid) and less predictable (Lissajous sinusoid) conditions and a free viewing scanpath task. Results. Individuals with schizophrenia demonstrated scanning deficits in both tasks. There was no association between performance measures of smooth pursuit and scene scanpaths in patient or control groups. Odds ratios comparing the likelihood of scanpath dysfunction when ETD was present, and the likelihood of finding scanpath dysfunction when ETD was absent were not significant in patients or controls in either pursuit variant, suggesting that ETD and scanpath dysfunction are independent anomalies in schizophrenia. Conclusion. ETD and scanpath disturbance appear to reflect independent oculomotor or neurocognitive deficits in schizophrenia. Each task may confer unique information about the pathophysiology of psychosis.
C1 [Beedie, Sara A.] Univ Aberdeen, Coll Life Sci & Med, Sch Psychol, Univ London Kings Coll, Aberdeen AB24 3FX, Scotland.
[Giegling, Ina; Rujescu, Dan] Univ Munich, Dept Psychiat, Div Mol & Clin Neurobiol, D-8000 Munich, Germany.
[St Clair, David M.] Univ Aberdeen, Dept Mental Hlth, Royal Cornhill Hosp, Aberdeen AB24 3FX, Scotland.
[St Clair, David M.] NIMH, Bethesda, MD 20892 USA.
RP Beedie, SA (reprint author), Univ Aberdeen, Coll Life Sci & Med, Sch Psychol, Univ London Kings Coll, William Guild Bldg, Aberdeen AB24 3FX, Scotland.
EM s.beedie@abdn.ac.uk
FU Royal Society of London; Millar-MacKenzie Trust; University of Aberdeen;
Chief Scientists Office [CZB-4-734]; European Commission
FX This manuscript is partly based on a doctoral dissertation completed by
SAB under the supervision of PJB and DSC. We are grateful to our
participants for their time. We are also grateful to Drs Nicholas Walker
and Sheila Gilfillan for facilitating patient recruitment in Scotland.
Data collection was supported by the Royal Society of London,
Millar-MacKenzie Trust, and the University of Aberdeen. During the
preparation of this manuscript, salary support for SAB has been provided
by the Chief Scientists Office (CZB-4-734, awarded to PJB) and
previously by the European Commission (SGENE, awarded to DSC).
Preliminary findings from this study were presented at the 2nd Biennial
Schizophrenia International Research Society Conference, 2010, Florence,
Italy.
NR 78
TC 3
Z9 3
U1 2
U2 5
PU INFORMA HEALTHCARE
PI LONDON
PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND
SN 1562-2975
J9 WORLD J BIOL PSYCHIA
JI World J. Biol. Psychiatry
PD MAR
PY 2012
VL 13
IS 3
BP 200
EP 210
DI 10.3109/15622975.2011.566628
PG 11
WC Psychiatry
SC Psychiatry
GA 908BC
UT WOS:000301464200005
PM 21545243
ER
PT J
AU Siberry, GK
Li, H
Jacobson, D
AF Siberry, George K.
Li, Hong
Jacobson, Denise
CA Pediat AIDS Clinical Trials Grp PA
TI Short Communication: Fracture Risk by HIV Infection Status in
Perinatally HIV-Exposed Children
SO AIDS RESEARCH AND HUMAN RETROVIRUSES
LA English
DT Article
ID BONE-MINERAL DENSITY; NAIVE PATIENTS; THERAPY; ADOLESCENTS; TENOFOVIR;
HEALTH; IMPACT; RATES
AB The objective of this study was to examine the incidence of fractures in HIV-infected children and comparable HIV-exposed, uninfected (HEU) children in a multicenter, prospective cohort study (PACTG 219/219C) in the United States. The main outcome was first fracture during the risk period. Nine fractures occurred in 7 of 1326 HIV-infected and 2 of 649 HEU children, corresponding to incidence rates of 1.2 per 1000 person-years and 1.1 per 1000 person-years, respectively. The incidence rate ratio was 1.1 (95% CI 0.2, 5.5). There was no evidence of a substantially increased risk of fracture in HIV-infected compared to HEU children.
C1 [Siberry, George K.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pediat Adolescent & Maternal AIDS PAMA Branch, Ctr Res Mothers & Children, NIH, Bethesda, MD 20892 USA.
[Li, Hong] Rush Univ, Dept Prevent Med, Chicago, IL 60612 USA.
[Jacobson, Denise] Harvard Univ, Sch Publ Hlth, Dept Biostat, Ctr Biostat AIDS Res CBAR, Boston, MA 02115 USA.
RP Siberry, GK (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pediat Adolescent & Maternal AIDS PAMA Branch, Ctr Res Mothers & Children, NIH, 6100 Execut Blvd,Room 4B11H, Bethesda, MD 20892 USA.
EM siberryg@mail.nih.gov
FU National Institute of Allergy and Infectious Diseases (NIAID) [U01
AI068632]; Eunice Kennedy Shriver National Institute of Child Health and
Human Development (NICHD); National Institute of Mental Health (NIMH)
[AI068632]; Statistical and Data Analysis Center at Harvard School of
Public Health under the National Institute of Allergy and Infectious
Diseases [5 U01 AI41110]; Pediatric AIDS Clinical Trials Group (PACTG)
[1 U01 AI068616]; National Institute of Allergy and Infectious Diseases
(NIAID); NICHD [N01-DK-9-001/HHSN267200800001C]
FX We thank the children and families for their participation in PACTG
219C, and the individuals and institutions involved in the conduct of
219C as well as the leadership and participants of the P219/219C
protocol team. Overall support for the International Maternal Pediatric
Adolescent AIDS Clinical Trials Group (IMPAACT) was provided by the
National Institute of Allergy and Infectious Diseases (NIAID) [U01
AI068632], the Eunice Kennedy Shriver National Institute of Child Health
and Human Development (NICHD), and the National Institute of Mental
Health (NIMH) [AI068632]. The content is solely the responsibility of
the authors and does not necessarily represent the official views of the
NIH. This work was supported by the Statistical and Data Analysis Center
at Harvard School of Public Health, under the National Institute of
Allergy and Infectious Diseases cooperative agreement # 5 U01 AI41110
with the Pediatric AIDS Clinical Trials Group (PACTG) and # 1 U01
AI068616 with the IMPAACT Group. Support of the sites was provided by
the National Institute of Allergy and Infectious Diseases (NIAID) and
the NICHD International and Domestic Pediatric and Maternal HIV Clinical
Trials Network funded by NICHD (contract number
N01-DK-9-001/HHSN267200800001C). We also thank the individual staff
members and sites who have participated in the conduct of this study.
NR 19
TC 7
Z9 7
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
J9 AIDS RES HUM RETROV
JI Aids Res. Hum. Retrovir.
PD MAR
PY 2012
VL 28
IS 3
BP 247
EP 250
DI 10.1089/aid.2011.0064
PG 4
WC Immunology; Infectious Diseases; Virology
SC Immunology; Infectious Diseases; Virology
GA 904VK
UT WOS:000301226100004
PM 22471877
ER
PT J
AU Prushik, SG
Farber, A
Gona, P
Shrader, P
Pencina, MJ
D'Agostino, RB
Murabito, JM
AF Prushik, Scott G.
Farber, Alik
Gona, Philimon
Shrader, Peter
Pencina, Michael J.
D'Agostino, Ralph B., Sr.
Murabito, Joanne M.
TI Parental Intermittent Claudication as Risk Factor for Claudication in
Adults
SO AMERICAN JOURNAL OF CARDIOLOGY
LA English
DT Article
ID PERIPHERAL ARTERIAL-DISEASE; ABDOMINAL AORTIC-ANEURYSM; GENOME-WIDE
ASSOCIATION; ANKLE-BRACHIAL INDEX; MIDDLE-AGED ADULTS;
CARDIOVASCULAR-DISEASE; CHROMOSOME 9P21.3; SEQUENCE VARIANT;
MYOCARDIAL-INFARCTION; FAMILY-HISTORY
AB Little is known about the familial aggregation of intermittent claudication (IC). Our objective was to examine whether parental IC increased the risk of IC in adult offspring, independent of the established cardiovascular risk factors. We evaluated the Offspring Cohort Participants of the Framingham Heart Study who were >= 30 years old, cardiovascular disease free, and had both parents enrolled in the Framingham Heart Study (n = 2,970 unique participants, 53% women). Pooled proportional hazards regression analysis was used to examine whether the 12-year risk of incident IC in offspring participants was associated with parental IC, adjusting for age, gender, diabetes, smoking, systolic blood pressure, total cholesterol, high-density lipoprotein cholesterol, and antihypertensive and lipid treatment. Of the 909 person-examinations in the parental IC history group and 5,397 person-examinations in the no-parental IC history group, there were 101 incident IC events (29 with parental IC history and 72 without a parental IC history) during follow-up. The age- and gender-adjusted 12-year cumulative incidence rate per 1,000 person-years was 5.08 (95% confidence interval [CI] 2.74 to 7.33) and 2.34 (95% CI 1.46 to 3.19) in participants with and without a parental IC history. A parental history of IC significantly increased the risk of incident IC in the offspring (multivariable adjusted hazard ratio 1.81,95% CI 1.14 to 2.88). The hazard ratio was unchanged, with an adjustment for the occurrence of cardiovascular disease (hazard ratio 1.83, 95% CI 1.15 to 2.91). In conclusion, IC in parents increases the risk of IC in adult offspring, independent of the established risk factors. These data suggest a genetic component of peripheral artery disease and support future research into genetic causes. (C) 2012 Elsevier Inc. All rights reserved. (Am J Cardiol 2012;109:736-741)
C1 [Gona, Philimon; Pencina, Michael J.; D'Agostino, Ralph B., Sr.; Murabito, Joanne M.] NHLBI, Framingham Heart Study, Framingham, MA USA.
[Prushik, Scott G.] Univ Massachusetts, Dept Vasc Surg, Worcester, MA USA.
[Murabito, Joanne M.] Boston Univ, Sch Med, Gen Internal Med Sect, Boston, MA 02118 USA.
[Farber, Alik] Boston Univ, Sch Med, Dept Vasc Surg, Boston, MA 02118 USA.
[Gona, Philimon; Shrader, Peter; Pencina, Michael J.; D'Agostino, Ralph B., Sr.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA.
[Gona, Philimon; Shrader, Peter; Pencina, Michael J.; D'Agostino, Ralph B., Sr.] New England Res Inst, Watertown, MA 02172 USA.
RP Murabito, JM (reprint author), NHLBI, Framingham Heart Study, Framingham, MA USA.
EM murabito@bu.edu
OI Murabito, Joanne/0000-0002-0192-7516
FU National Heart, Lung, and Blood Institute's Framingham Heart Study
(Bethesda, Maryland) [N01-HC-25195]
FX This work was supported by grant N01-HC-25195 from the National Heart,
Lung, and Blood Institute's Framingham Heart Study (Bethesda, Maryland).
NR 30
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
J9 AM J CARDIOL
JI Am. J. Cardiol.
PD MAR 1
PY 2012
VL 109
IS 5
BP 736
EP 741
DI 10.1016/j.amjcard.2011.10.032
PG 6
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 907CA
UT WOS:000301394200023
PM 22154319
ER
PT J
AU Davis, BM
Aiello, AE
Dawid, S
Rohani, P
Shrestha, S
Foxman, B
AF Davis, Brian M.
Aiello, Allison E.
Dawid, Suzanne
Rohani, Pejman
Shrestha, Sourya
Foxman, Betsy
TI Influenza and Community-acquired Pneumonia Interactions: The Impact of
Order and Time of Infection on Population Patterns
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Editorial Material
DE community-acquired infections; influenza, human; pneumococcal
infections; pneumonia
ID STREPTOCOCCUS-PNEUMONIAE; BACTERIAL PNEUMONIA; STAPHYLOCOCCUS-AUREUS;
PANDEMIC INFLUENZA; UNITED-STATES; VIRUS; DISEASE; DEATH;
SUSCEPTIBILITY; COLONIZATION
AB Discoveries made during the 1918 influenza A pandemic and reports of severe disease associated with coinfection during the 2009 hemagglutinin type 1 and neuraminidase type 1 (commonly known as H1N1 or swine flu) pandemic have renewed interest in the role of coinfection in disease pathogenesis. The authors assessed how various timings of coinfection with influenza virus and pneumonia-causing bacteria could affect the severity of illness at multiple levels of interaction, including the biologic and population levels. Animal studies most strongly support a single pathway of coinfection with influenza inoculation occurring approximately 7 days before inoculation with Streptococcus pneumoniae, but less-examined pathways of infection also may be important for human disease. The authors discussed the implications of each pathway for disease prevention and what they would expect to see at the population level if there were sufficient data available. Lastly, the authors identified crucial gaps in the study of timing of coinfection and proposed related research questions.
C1 [Aiello, Allison E.; Foxman, Betsy] Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ctr Mol & Clin Epidemiol Infect Dis, Ann Arbor, MI 48109 USA.
[Davis, Brian M.; Aiello, Allison E.] Univ Michigan, Sch Publ Hlth, Ctr Social Epidemiol & Populat Hlth, Ann Arbor, MI 48109 USA.
[Dawid, Suzanne] Univ Michigan, Sch Med, Dept Pediat & Communicable Dis, Ann Arbor, MI USA.
[Dawid, Suzanne] Univ Michigan, Sch Med, Dept Microbiol & Immunol, Ann Arbor, MI 48109 USA.
[Rohani, Pejman; Shrestha, Sourya] Univ Michigan, Dept Ecol & Evolutionary Biol, Ann Arbor, MI 48109 USA.
[Rohani, Pejman; Shrestha, Sourya] Univ Michigan, Coll Literature Sci & Arts, Ctr Study Complex Syst, Ann Arbor, MI 48109 USA.
[Rohani, Pejman] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Foxman, B (reprint author), Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ctr Mol & Clin Epidemiol Infect Dis, 1415 Washington Hts, Ann Arbor, MI 48109 USA.
EM bfoxman@umich.edu
OI Shrestha, Sourya/0000-0002-6106-6834; Foxman, Betsy/0000-0001-6682-238X
NR 37
TC 6
Z9 7
U1 1
U2 3
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0002-9262
EI 1476-6256
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD MAR 1
PY 2012
VL 175
IS 5
BP 363
EP 367
DI 10.1093/aje/kwr402
PG 5
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 898GT
UT WOS:000300728800001
PM 22247048
ER
PT J
AU Gaskins, AJ
Wilchesky, M
Mumford, SL
Whitcomb, BW
Browne, RW
Wactawski-Wende, J
Perkins, NJ
Schisterman, EF
AF Gaskins, Audrey J.
Wilchesky, Machelle
Mumford, Sunni L.
Whitcomb, Brian W.
Browne, Richard W.
Wactawski-Wende, Jean
Perkins, Neil J.
Schisterman, Enrique F.
TI Endogenous Reproductive Hormones and C-reactive Protein Across the
Menstrual Cycle
SO AMERICAN JOURNAL OF EPIDEMIOLOGY
LA English
DT Article
DE estrogens; inflammation; menstrual cycle
ID MARGINAL STRUCTURAL MODELS; CORONARY HEART-DISEASE;
CARDIOVASCULAR-DISEASE; TRANSDERMAL ESTRADIOL; GENE-EXPRESSION; WOMEN;
ESTROGEN; INFLAMMATION; MARKERS; 17-BETA-ESTRADIOL
AB Creactive protein (CRP) is one of the most commonly used markers of acute phase reaction in clinical settings and predictors of cardiovascular risk in healthy women; however, data on its physiologic regulation in premenopausal women are sparse. The objective of this study was to evaluate the association between endogenous reproductive hormones and CRP in the BioCycle Study (2005-2007). Women aged 18-44 years from western New York were followed prospectively for up to 2 menstrual cycles (n = 259). Serum levels of CRP, estradiol, progesterone, luteinizing hormone, and follicle-stimulating hormone were measured up to 8 times per cycle, timed by fertility monitors. CRP levels varied significantly across the cycle (P < 0.001). More women were classified as being at elevated risk of cardiovascular disease (CRP, >3 mg/L) during menses compared with other phases (12.3% vs. 7.4%; P < 0.001). A 10-fold increase in estradiol was associated with a 24.3% decrease in CRP (95% confidence interval: 19.3, 29.0). A 10-fold increase in luteal progesterone was associated with a 19.4% increase in CRP (95% confidence interval: 8.4, 31.5). These results support the hypothesis that endogenous estradiol might have antiinflammatory effects and highlight the need for standardization of CRP measurement to menstrual cycle phase in reproductive-aged women.
C1 [Schisterman, Enrique F.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, Rockville, MD 20852 USA.
[Wilchesky, Machelle] McGill Univ, Montreal Childrens Hosp, Res Inst, Montreal, PQ H3H 1P3, Canada.
[Whitcomb, Brian W.] Univ Massachusetts, Sch Publ Hlth & Hlth Sci, Div Biostat & Epidemiol, Amherst, MA 01003 USA.
[Browne, Richard W.] SUNY Buffalo, Dept Biotech & Clin Lab Sci, Buffalo, NY 14260 USA.
[Wactawski-Wende, Jean] SUNY Buffalo, Dept Social & Preventat Med, Buffalo, NY 14260 USA.
RP Schisterman, EF (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, 6100 Execut Blvd,Room 7B03M, Rockville, MD 20852 USA.
EM schistee@mail.nih.gov
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development, National Institutes of Health
FX This work was supported by the Intramural Research Program of the Eunice
Kennedy Shriver National Institute of Child Health and Human
Development, National Institutes of Health.
NR 40
TC 28
Z9 29
U1 4
U2 7
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 0002-9262
J9 AM J EPIDEMIOL
JI Am. J. Epidemiol.
PD MAR 1
PY 2012
VL 175
IS 5
BP 423
EP 431
DI 10.1093/aje/kwr343
PG 9
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 898GT
UT WOS:000300728800009
PM 22306563
ER
PT J
AU McBride, CM
Bryan, AD
Bray, MS
Swan, GE
Green, ED
AF McBride, Colleen M.
Bryan, Angela D.
Bray, Molly S.
Swan, Gary E.
Green, Eric D.
TI Health Behavior Change: Can Genomics Improve Behavioral Adherence?
SO AMERICAN JOURNAL OF PUBLIC HEALTH
LA English
DT Editorial Material
ID GENETIC INFORMATION; RISK-FACTORS; TOBACCO USE; EXERCISE; WEIGHT;
INTERVENTIONS; MANAGEMENT; GENOTYPES; MEDICINE; SMOKING
C1 [McBride, Colleen M.; Green, Eric D.] NHGRI, Bethesda, MD 20892 USA.
[Bryan, Angela D.] Univ New Mexico, Dept Psychol, Albuquerque, NM 87131 USA.
[Swan, Gary E.] SRI Int, Ctr Hlth Sci, Menlo Pk, CA 94025 USA.
[Bray, Molly S.] Univ Alabama, Sch Publ Hlth, Birmingham, AL USA.
RP McBride, CM (reprint author), NHGRI, 31 Ctr Dr,Bldg 31,Room B1B54B, Bethesda, MD 20892 USA.
EM cmcbride@mail.nih.gov
FU NIDDK NIH HHS [R01 DK062148]
NR 46
TC 26
Z9 28
U1 2
U2 22
PU AMER PUBLIC HEALTH ASSOC INC
PI WASHINGTON
PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA
SN 0090-0036
J9 AM J PUBLIC HEALTH
JI Am. J. Public Health
PD MAR
PY 2012
VL 102
IS 3
BP 401
EP 405
DI 10.2105/AJPH.2011.300513
PG 5
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 893EN
UT WOS:000300338500010
PM 22390502
ER
PT J
AU Driscoll, JJ
Burris, J
Annunziata, CM
AF Driscoll, James J.
Burris, Jason
Annunziata, Christina M.
TI Targeting the Proteasome With Bortezomib in Multiple Myeloma: Update on
Therapeutic Benefit as an Upfront Single Agent, Induction Regimen for
Stem-Cell Transplantation and as Maintenance Therapy
SO AMERICAN JOURNAL OF THERAPEUTICS
LA English
DT Article
DE multiple myeloma; bortezomib; monotherapy; stem-cell transplantation
induction; maintenance therapy
ID PHASE-II; INCORPORATING BORTEZOMIB; NEDD8-ACTIVATING ENZYME; COMBINATION
THERAPY; PLUS DEXAMETHASONE; CLINICAL-OUTCOMES; TRIAL; EXPRESSION;
LENALIDOMIDE; CHEMOTHERAPY
AB Bortezomib is the first therapeutic inhibitor of the proteasome that has demonstrated a significant clinical response in patients with otherwise refractory or rapidly advancing disease. Bortezomib has received US Federal Drug Administration approval for the treatment of the hematologic malignancies such as multiple myeloma and mantle cell lymphoma. Herein, the use of bortezomib as an upfront therapy, as an induction regimen before stem-cell transplantation and as maintenance therapy in the treatment of multiple myeloma is discussed.
C1 [Driscoll, James J.; Burris, Jason; Annunziata, Christina M.] NCI, Med Oncol Branch, Magnuson Canc Ctr, NIH,Translat Genom Sect, Bethesda, MD 20892 USA.
[Burris, Jason] Walter Reed Army Med Ctr, Dept Med, Hematol Oncol Serv, Washington, DC 20307 USA.
RP Driscoll, JJ (reprint author), NCI, Med Oncol Branch, Magnuson Canc Ctr, NIH,Translat Genom Sect, 10 Ctr Dr,Bldg 10,Room 12N-226, Bethesda, MD 20892 USA.
EM driscollj@mail.nih.gov
RI Annunziata, Christina/L-3219-2016
OI Annunziata, Christina/0000-0003-2033-6532
FU Intramural NIH HHS [ZIA BC011312-02]
NR 64
TC 4
Z9 4
U1 1
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 1075-2765
EI 1536-3686
J9 AM J THER
JI Am. J. Ther.
PD MAR
PY 2012
VL 19
IS 2
BP 133
EP 144
DI 10.1097/MJT.0b013e3181ff7a9e
PG 12
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 906GW
UT WOS:000301333900017
PM 21248621
ER
PT J
AU Murphy, SC
Prentice, JL
Williamson, K
Wallis, CK
Fang, FC
Fried, M
Pinzon, C
Wang, RB
Talley, AK
Kappe, SHI
Duffy, PE
Cookson, BT
AF Murphy, Sean C.
Prentice, Jennifer L.
Williamson, Kathryn
Wallis, Carolyn K.
Fang, Ferric C.
Fried, Michal
Pinzon, Cris
Wang, Ruobing
Talley, Angela K.
Kappe, Stefan H. I.
Duffy, Patrick E.
Cookson, Brad T.
TI Real-Time Quantitative Reverse Transcription PCR for Monitoring of
Blood-Stage Plasmodium falciparum Infections in Malaria Human Challenge
Trials
SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE
LA English
DT Article
ID POLYMERASE-CHAIN-REACTION; SEQUENCE-BASED AMPLIFICATION; VACCINIA VIRUS
ANKARA; RIBOSOMAL-RNA GENES; RAPID DIAGNOSTIC-TESTS; ERYTHROCYTIC
STAGES; CLINICAL-DIAGNOSIS; ENDEMIC AREA; NESTED PCR; ASSAY
AB To detect pre-patent parasitemia, we developed a real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) for the asexual 18S ribosomal RNA (rRNAs) of Plasmodium falciparum. Total nucleic acids extracted from whole blood were combined with control RNA and tested by qRT-PCR. The assay quantified > 98.7% of parasite-containing samples to +/- 0.5 log(10) parasites/mL of the nominal value without false positives. The analytical sensitivity was >= 20 parasites/mL. The coefficient of variation was 0.6% and 1.8% within runs and 1.6% and 4.0% between runs for high and low parasitemia specimens, respectively. Using this assay, we determined that A-type 18S rRNAs are stably expressed at 1 x 10(4) copies per ring-stage parasite. When used to monitor experimental P. falciparum infection of human volunteers, the assay detected blood-stage infections 3.7 days earlier on average than thick blood smears. This validated, internally controlled qRT-PCR method also uses a small (50 mu L) sample volume requiring minimal pre-analytical handling, making it useful for clinical trials.
C1 Univ Washington, Med Ctr, Dept Lab Med Microbiol & Med, Div Allergy & Infect Dis, Seattle, WA 98195 USA.
Seattle Biomed Res Inst, Malaria Clin Trials Ctr, Seattle, WA 98109 USA.
NIAID, NIH, Bethesda, MD 20892 USA.
RP Murphy, SC (reprint author), Univ Washington, Med Ctr, Dept Lab Med, 1959 NE Pacific St,Box 357110, Seattle, WA 98195 USA.
EM murphysc@u.washington.edu
OI Fang, Ferric/0000-0002-3243-110X
FU PATH Malaria Vaccine Initiative; U.S. Department of Defense
[W81XWH-09-1-0531]; U.S. Army Medical Research Acquisition Activity
FX Funding in support of the human challenge trial was provided by the PATH
Malaria Vaccine Initiative and the U.S. Department of Defense (award no.
W81XWH-09-1-0531; the U.S. Army Medical Research Acquisition Activity,
820 Chandler Street, Fort Detrick, MD 21702-5014 is the awarding and
administering acquisition office).
NR 51
TC 25
Z9 26
U1 0
U2 5
PU AMER SOC TROP MED & HYGIENE
PI MCLEAN
PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA
SN 0002-9637
J9 AM J TROP MED HYG
JI Am. J. Trop. Med. Hyg.
PD MAR
PY 2012
VL 86
IS 3
BP 383
EP 394
DI 10.4269/ajtmh.2012.10-0658
PG 12
WC Public, Environmental & Occupational Health; Tropical Medicine
SC Public, Environmental & Occupational Health; Tropical Medicine
GA 904AM
UT WOS:000301166000003
PM 22403305
ER
PT J
AU Alkhalil, A
Hong, L
Nguitragool, W
Desai, SA
AF Alkhalil, Abdulnaser
Hong, Liang
Nguitragool, Wang
Desai, Sanjay A.
TI Voltage-dependent inactivation of the plasmodial surface anion channel
via a cleavable cytoplasmic component
SO BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES
LA English
DT Article
DE PSAC; Voltage-dependent inactivation; Patch-clamp; Malaria; Antimalarial
drug targets; Clag genes
ID RED-BLOOD-CELLS; MALARIA PARASITE; HUMAN ERYTHROCYTES; CHLORIDE CHANNEL;
NUTRIENT-UPTAKE; SODIUM-CHANNEL; SQUID AXONS; FALCIPARUM; MEMBRANE;
CONDUCTANCE
AB Erythrocytes infected with malaria parasites have increased permeability to ions and various nutrient solutes, mediated by a parasite ion channel known as the plasmodial surface anion channel (PSAC). The parasite clag3 gene family encodes PSAC activity, but there may also be additional unidentified components of this channel. Consistent with a lack of clag3 homology to genes of other ion channels. PSAC has a number of unusual functional properties. Here, we report that PSAC exhibits an unusual form of voltage-dependent inactivation. Inactivation was readily detected in the whole-cell patch-clamp configuration after steps to negative membrane potentials. The fraction of current that inactivates, its kinetics, and the rate of recovery were all voltage-dependent, though with a modest effective valence (0.7 +/- 0.1 elementary charges). These properties were not affected by solution composition or charge carrier, suggesting inactivation intrinsic to the channel protein. Intriguingly, inactivation was absent in cell-attached recordings and took several minutes to appear after obtaining the whole-cell configuration, suggesting interactions with soluble cytosolic components. Inactivation could also be largely abolished by application of intracellular, but not extracellular protease. The findings implicate inactivation via a charged cytoplasmic channel domain. This domain may be tethered to one or more soluble intracellular components under physiological conditions. Published by Elsevier B.V.
C1 [Alkhalil, Abdulnaser; Hong, Liang; Nguitragool, Wang; Desai, Sanjay A.] NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA.
RP Desai, SA (reprint author), NIAID, Lab Malaria & Vector Res, NIH, Room 3W-01,12735 Twinbrook Pkwy, Rockville, MD 20852 USA.
EM sdesai@niaid.nih.gov
RI Hong, Liang/C-4251-2008
OI Hong, Liang/0000-0001-8152-5631
FU National Institutes of Health, National Institute of Allergy and
Infectious Diseases
FX We thank Ajay D. Pillai for comments on the manuscript. This research
was supported by the Intramural Research Program of the National
Institutes of Health, National Institute of Allergy and Infectious
Diseases.
NR 36
TC 5
Z9 5
U1 0
U2 8
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0005-2736
J9 BBA-BIOMEMBRANES
JI Biochim. Biophys. Acta-Biomembr.
PD MAR
PY 2012
VL 1818
IS 3
BP 367
EP 374
DI 10.1016/j.bbamem.2011.11.010
PG 8
WC Biochemistry & Molecular Biology; Biophysics
SC Biochemistry & Molecular Biology; Biophysics
GA 903XI
UT WOS:000301155600003
PM 22115742
ER
PT J
AU Cooper-Knock, J
Hewitt, C
Highley, JR
Brockington, A
Milano, A
Man, S
Martindale, J
Hartley, J
Walsh, T
Gelsthorpe, C
Baxter, L
Forster, G
Fox, M
Bury, J
Mok, K
McDermott, CJ
Traynor, BJ
Kirby, J
Wharton, SB
Ince, PG
Hardy, J
Shaw, PJ
AF Cooper-Knock, Johnathan
Hewitt, Christopher
Highley, J. Robin
Brockington, Alice
Milano, Antonio
Man, Somai
Martindale, Joanne
Hartley, Judith
Walsh, Theresa
Gelsthorpe, Catherine
Baxter, Lynne
Forster, Gillian
Fox, Melanie
Bury, Joanna
Mok, Kin
McDermott, Christopher J.
Traynor, Bryan J.
Kirby, Janine
Wharton, Stephen B.
Ince, Paul G.
Hardy, John
Shaw, Pamela J.
TI Clinico-pathological features in amyotrophic lateral sclerosis with
expansions in C9ORF72
SO BRAIN
LA English
DT Article
DE amyotrophic lateral sclerosis; C9ORF72; dementia; neurodegeneration
ID FRONTOTEMPORAL DEMENTIA; MUTATIONS; TDP-43; ALS; PATHOLOGY; OPTINEURIN;
INCLUSIONS; DISEASES
AB Intronic expansion of the GGGGCC hexanucleotide repeat within the C9ORF72 gene causes frontotemporal dementia and amyotrophic lateral sclerosis/motor neuron disease in both familial and sporadic cases. Initial reports indicate that this variant within the frontotemporal dementia/amyotrophic lateral sclerosis spectrum is associated with transactive response DNA binding protein (TDP-43) proteinopathy. The amyotrophic lateral sclerosis/motor neuron disease phenotype is not yet well characterized. We report the clinical and pathological phenotypes associated with pathogenic C9ORF72 mutations in a cohort of 563 cases from Northern England, including 63 with a family history of amyotrophic lateral sclerosis. One hundred and fifty-eight cases from the cohort (21 familial, 137 sporadic) were post-mortem brain and spinal cord donors. We screened DNA for the C9ORF72 mutation, reviewed clinical case histories and undertook pathological evaluation of brain and spinal cord. Control DNA samples (n = 361) from the same population were also screened. The C9ORF72 intronic expansion was present in 62 cases [11% of the cohort; 27/63 (43%) familial, 35/500 (7%) cases with sporadic amyotrophic lateral sclerosis/motor neuron disease]. Disease duration was significantly shorter in cases with C9ORF72-related amyotrophic lateral sclerosis (30.5 months) compared with non-C9ORF72 amyotrophic lateral sclerosis/motor neuron disease (36.3 months, P < 0.05). C9ORF72 cases included both limb and bulbar onset disease and all cases showed combined upper and lower motor neuron degeneration (amyotrophic lateral sclerosis). Thus, clinically, C9ORF72 cases show the features of a relatively rapidly progressive, but otherwise typical, variant of amyotrophic lateral sclerosis associated with both familial and sporadic presentations. Dementia was present in the patient or a close family member in 22/62 cases with C9ORF72 mutation (35%) based on diagnoses established from retrospective clinical case note review that may underestimate significant cognitive changes in late disease. All the C9ORF72 mutation cases showed classical amyotrophic lateral sclerosis pathology with TDP-43 inclusions in spinal motor neurons. Neuronal cytoplasmic inclusions and glial inclusions positive for p62 immunostaining in non-motor regions were strongly over-represented in the C9ORF72 cases. Extra-motor pathology in the frontal cortex (P < 0.0005) and the hippocampal CA4 subfield neurons (P < 0.0005) discriminated C9ORF72 cases strongly from the rest of the cohort. Inclusions in CA4 neurons were not present in non-C9ORF72 cases, indicating that this pathology predicts mutation status.
C1 [Cooper-Knock, Johnathan; Hewitt, Christopher; Highley, J. Robin; Brockington, Alice; Hartley, Judith; Walsh, Theresa; Gelsthorpe, Catherine; Baxter, Lynne; Forster, Gillian; Fox, Melanie; Bury, Joanna; McDermott, Christopher J.; Kirby, Janine; Wharton, Stephen B.; Ince, Paul G.; Shaw, Pamela J.] Univ Sheffield, Sheffield Inst Translat Neurosci SITraN, Sheffield S10 2HQ, S Yorkshire, England.
[Milano, Antonio; Man, Somai; Martindale, Joanne] Sheffield Childrens NHS Fdn Trust, Sheffield Diagnost Genet Serv, Western Bank, Sheffield S10 2TH, S Yorkshire, England.
[Mok, Kin; Hardy, John] UCL, Inst Neurol, Dept Mol Neurosci, London WC1N IPJ, England.
[Mok, Kin; Hardy, John] UCL, Inst Neurol, Reta Lila Weston Labs, London WC1N IPJ, England.
[Traynor, Bryan J.] NIA, Neuromuscular Dis Res Unit, Neurogenet Lab, NIH, Bethesda, MD 20892 USA.
[Traynor, Bryan J.] Johns Hopkins Univ, Brain Sci Inst, Dept Neurol, Baltimore, MD 21287 USA.
RP Shaw, PJ (reprint author), Univ Sheffield, Sheffield Inst Translat Neurosci SITraN, 385A Glossop Rd, Sheffield S10 2HQ, S Yorkshire, England.
EM pamela.shaw@sheffield.ac.uk
RI Hardy, John/C-2451-2009; Mok, Kin/F-5860-2012; Traynor,
Bryan/G-5690-2010; Brockington, Alice/B-5122-2009;
OI Highley, Robin/0000-0002-4969-6526; Kirby, Janine/0000-0002-7468-5917;
Cooper-Knock, Johnathan/0000-0002-0873-8689
FU European Community [259867]; MND Association [Shaw/Nov02/6700/3];
Wellcome Trust [WT070122MF]; MND Association/Medical Research Council
[G0 800380]; Wellcome Trust/MRC [WT 089698/Z/09/Z]; NIH, National
Institute on Aging [Z01-AG000949-02]; National Institute for
Neurological Disorders and Stroke
FX European Community's Health 7th Framework Programme (FP 7 2007-2013
under grant agreement no. 259867 to P.J.S. and J.K.). MND Association
(Shaw/Nov02/6700/3 to P.J.S.); Wellcome Trust (WT070122MF to P.J.S.);
MND Association/Medical Research Council Lady Edith Wolfson Fellowship
award (G0 800380 to J.R.H.); Wellcome Trust/MRC Strategic
Neurodegeneration Award (WT 089698/Z/09/Z to J.H.) and Intramural
Research Programs of the NIH, National Institute on Aging
(Z01-AG000949-02 to B.J.T.) and National Institute for Neurological
Disorders and Stroke (to B.J.T.).
NR 36
TC 124
Z9 127
U1 3
U2 35
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 MAR
PY 2012
VL 135
BP 751
EP 764
DI 10.1093/brain/awr365
PN 3
PG 14
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 898JI
UT WOS:000300738300009
PM 22366792
ER
PT J
AU Chio, A
Borghero, G
Restagno, G
Mora, G
Drepper, C
Traynor, BJ
Sendtner, M
Brunetti, M
Ossola, I
Calvo, A
Pugliatti, M
Sotgiu, MA
Murru, MR
Marrosu, MG
Marrosu, F
Marinou, K
Mandrioli, J
Sola, P
Caponnetto, C
Mancardi, G
Mandich, P
La Bella, V
Spataro, R
Conte, A
Monsurro, MR
Tedeschi, G
Pisano, F
Bartolomei, I
Salvi, F
Pinter, GL
Simone, I
Logroscino, G
Gambardella, A
Quattrone, A
Lunetta, C
Volanti, P
Zollino, M
Penco, S
Battistini, S
Renton, AE
Majounie, E
Abramzon, Y
Conforti, FL
Giannini, F
Corbo, M
Sabatelli, M
AF Chio, Adriano
Borghero, Giuseppe
Restagno, Gabriella
Mora, Gabriele
Drepper, Carsten
Traynor, Bryan J.
Sendtner, Michael
Brunetti, Maura
Ossola, Irene
Calvo, Andrea
Pugliatti, Maura
Sotgiu, Maria Alessandra
Murru, Maria Rita
Marrosu, Maria Giovanna
Marrosu, Francesco
Marinou, Kalliopi
Mandrioli, Jessica
Sola, Patrizia
Caponnetto, Claudia
Mancardi, Gianluigi
Mandich, Paola
La Bella, Vincenzo
Spataro, Rossella
Conte, Amelia
Monsurro, Maria Rosaria
Tedeschi, Gioacchino
Pisano, Fabrizio
Bartolomei, Ilaria
Salvi, Fabrizio
Pinter, Giuseppe Lauria
Simone, Isabella
Logroscino, Giancarlo
Gambardella, Antonio
Quattrone, Aldo
Lunetta, Christian
Volanti, Paolo
Zollino, Marcella
Penco, Silvana
Battistini, Stefania
Renton, Alan E.
Majounie, Elisa
Abramzon, Yevgeniya
Conforti, Francesca Luisa
Giannini, Fabio
Corbo, Massimo
Sabatelli, Mario
CA ITALSGEN Consortium
TI Clinical characteristics of patients with familial amyotrophic lateral
sclerosis carrying the pathogenic GGGGCC hexanucleotide repeat expansion
of C9ORF72
SO BRAIN
LA English
DT Article
DE amyotrophic lateral sclerosis; familial ALS; C9ORF72 gene;
phenotype-genotype correlation
ID TARDBP MUTATIONS; ALS; POPULATION; DISEASE; DEMENTIA; FTD
AB A large hexanucleotide (GGGGCC) repeat expansion in the first intron of C9ORF72, a gene located on chromosome 9p21, has been recently reported to be responsible for similar to 40% of familial amyotrophic lateral sclerosis cases of European ancestry. The aim of the current article was to describe the phenotype of amyotrophic lateral sclerosis cases carrying the expansion by providing a detailed clinical description of affected cases from representative multi-generational kindreds, and by analysing the age of onset, gender ratio and survival in a large cohort of patients with familial amyotrophic lateral sclerosis. We collected DNA and analysed phenotype data for 141 index Italian familial amyotrophic lateral sclerosis cases (21 of Sardinian ancestry) and 41 German index familial amyotrophic lateral sclerosis cases. Pathogenic repeat expansions were detected in 45 (37.5%) patients from mainland Italy, 12 (57.1%) patients of Sardinian ancestry and nine (22.0%) of the 41 German index familial amyotrophic lateral sclerosis cases. The disease was maternally transmitted in 27 (49.1%) pedigrees and paternally transmitted in 28 (50.9%) pedigrees (P = non-significant). On average, children developed disease 7.0 years earlier than their parents [children: 55.8 years (standard deviation 7.9), parents: 62.8 (standard deviation 10.9); P = 0.003]. Parental phenotype influenced the type of clinical symptoms manifested by the child: of the 13 cases where the affected parent had an amyotrophic lateral sclerosis-frontotemporal dementia or frontotemporal dementia, the affected child also developed amyotrophic lateral sclerosis-frontotemporal dementia in nine cases. When compared with patients carrying mutations of other amyotrophic lateral sclerosis-related genes, those with C9ORF72 expansion had commonly a bulbar onset (42.2% compared with 25.0% among non-C9ORF72 expansion cases, P = 0.03) and cognitive impairment (46.7% compared with 9.1% among non-C9ORF72 expansion cases, P = 0.0001). Median survival from symptom onset among cases carrying C9ORF72 repeat expansion was 3.2 years lower than that of patients carrying TARDBP mutations (5.0 years; 95% confidence interval: 3.6-7.2) and longer than those with FUS mutations (1.9 years; 95% confidence interval: 1.7-2.1). We conclude that C9ORF72 hexanucleotide repeat expansions were the most frequent mutation in our large cohort of patients with familial amyotrophic lateral sclerosis of Italian, Sardinian and German ancestry. Together with mutation of SOD1, TARDBP and FUS, mutations of C9ORF72 account for similar to 60% of familial amyotrophic lateral sclerosis in Italy. Patients with C9ORF72 hexanucleotide repeat expansions present some phenotypic differences compared with patients with mutations of other genes or with unknown mutations, namely a high incidence of bulbar-onset disease and comorbidity with frontotemporal dementia. Their pedigrees typically display a high frequency of cases with pure frontotemporal dementia, widening the concept of familial amyotrophic lateral sclerosis.
C1 [Chio, Adriano; Calvo, Andrea] Univ Turin, Dept Neurosci, I-10126 Turin, Italy.
[Chio, Adriano; Calvo, Andrea] Azienda Osped Univ San Giovanni Battista Turin, I-10126 Turin, Italy.
[Borghero, Giuseppe; Marrosu, Francesco] Azienda Univ Osped Cagliari, I-09100 Cagliari, Italy.
[Borghero, Giuseppe] Univ Cagliari, I-09100 Cagliari, Italy.
[Restagno, Gabriella; Brunetti, Maura; Ossola, Irene] ASO OIRM St Anna, Mol Genet Unit, Dept Clin Pathol, I-10126 Turin, Italy.
[Drepper, Carsten; Sendtner, Michael] Univ Wurzburg, Inst Clin Neurobiol, D-97018 Wurzburg, Germany.
[Traynor, Bryan J.; Renton, Alan E.; Abramzon, Yevgeniya] NIA, Neuromuscular Dis Res Unit, Neurogenet Lab, NIH, Bethesda, MD 20894 USA.
[Pugliatti, Maura] Univ Sassari, Dept Neurosci, I-07100 Sassari, Italy.
[Sotgiu, Maria Alessandra] Univ Sassari, Dept Biomed Sci, I-07100 Sassari, Italy.
[Murru, Maria Rita; Marrosu, Maria Giovanna] Univ Cagliari, Ctr Sclerosi Multipla, Osped Binaghi, I-09100 Cagliari, Italy.
[Mandrioli, Jessica; Sola, Patrizia] Univ Modena, St Agostino Estense Hosp, Dept Neurosci, I-41126 Modena, Italy.
[Mora, Gabriele; Marinou, Kalliopi] Salvatore Maugeri Fdn IRCSS, Sci Inst Milan, I-20138 Milan, Italy.
[Caponnetto, Claudia; Mancardi, Gianluigi; Mandich, Paola] Univ Genoa, Dept Neurosci Ophthalmol & Genet, I-16132 Genoa, Italy.
[La Bella, Vincenzo; Spataro, Rossella] Univ Palermo, Dept Neurosci, ALS Clin Res Ctr, Bio Ne C, I-90100 Palermo, Italy.
[Conte, Amelia; Sabatelli, Mario] Catholic Univ, Neurol Inst, I-00168 Rome, Italy.
[Conte, Amelia; Sabatelli, Mario] I CO MM Assoc ALS Res, I-00168 Rome, Italy.
[Monsurro, Maria Rosaria; Tedeschi, Gioacchino] Univ Naples 2, Dept Neurol Sci, I-80138 Naples, Italy.
[Pisano, Fabrizio] Salvatore Maugeri Fdn IRCSS, Sci Inst Veruno, I-28010 Veruno, NO, Italy.
[Bartolomei, Ilaria; Salvi, Fabrizio] Bellaria Hosp, Dept Neurol, Ctr Diag & Cure Rare Dis, I-40139 Bologna, Italy.
[Pinter, Giuseppe Lauria] Natl Neurol Inst Besta, Dept Neurol, I-20133 Milan, Italy.
[Simone, Isabella; Logroscino, Giancarlo] Univ Bari, Dept Neurosci, I-70100 Bari, Italy.
[Gambardella, Antonio; Quattrone, Aldo; Conforti, Francesca Luisa] CNR, Inst Neurol Sci, I-87050 Cosenza, Italy.
[Lunetta, Christian; Corbo, Massimo] Serena Fdn, Neuromuscular OnmiCtr, I-20162 Milan, Italy.
[Volanti, Paolo] Salvatore Maugeri Fdn IRCSS, Sci Inst Mistretta, I-98073 Mistretta, ME, Italy.
[Zollino, Marcella] Catholic Univ, Dept Lab Med, Mol Genet Lab, I-00168 Rome, Italy.
[Penco, Silvana] Osped Niguarda Ca Granda, Dept Lab Med, I-20162 Milan, Italy.
[Battistini, Stefania; Giannini, Fabio] Univ Siena, Neurol Sect, Dept Neurosci, I-53100 Siena, Italy.
[Majounie, Elisa] NIA, Neurogenet Lab, Mol Genet Unit, Bethesda, MD 20892 USA.
RP Chio, A (reprint author), Univ Turin, Dept Neurosci, Via Cherasco 15, I-10126 Turin, Italy.
EM achio@usa.net
RI MANDRIOLI, JESSICA/K-7235-2016; Conforti, Francesca Luisa/K-8877-2016;
mancardi, giovanni luigi/K-8656-2016; Traynor, Bryan/G-5690-2010;
Battistini, Stefania/N-2596-2015; QUATTRONE, Aldo/A-6734-2016; Calvo,
Andrea/K-4141-2016; LOGROSCINO, GIANCARLO/K-5148-2016; Spataro,
Rossella/B-3656-2016; Lunetta, Christian/K-9214-2016; Sendtner,
Michael/J-1542-2012; La Bella, Vincenzo/H-4532-2012; Moglia,
Cristina/K-4142-2016
OI MANDRIOLI, JESSICA/0000-0002-9244-9782; Sabatelli,
Mario/0000-0001-6635-4985; Conforti, Francesca
Luisa/0000-0001-8364-1783; mancardi, giovanni luigi/0000-0001-8427-118X;
Chio, Adriano/0000-0001-9579-5341; Cammarosano,
Stefania/0000-0002-0981-5252; Penco, Silvana/0000-0003-1050-095X;
SOLINAS, GIULIANA/0000-0003-2174-0983; Marrosu, Maria
Giovanna/0000-0003-2334-2081; Gambardella , Antonio/0000-0001-7384-3074;
Battistini, Stefania/0000-0003-2887-7624; QUATTRONE,
Aldo/0000-0003-2001-957X; Calvo, Andrea/0000-0002-5122-7243; LOGROSCINO,
GIANCARLO/0000-0003-0423-3242; Spataro, Rossella/0000-0002-8910-3131;
Lunetta, Christian/0000-0002-4788-1875; Sendtner,
Michael/0000-0002-4737-2974; Mandich, Paola/0000-0003-3123-3512; Moglia,
Cristina/0000-0001-7377-7222
FU Federazione Italiana Giuoco Calcio; Fondazione Vialli e Mauro per la
Sclerosi Laterale Amiotrofica onlus; Ministero della Salute (Ricerca
Sanitaria Finalizzata); European Community [FP7/2007-2013, 259867];
National Institutes of Health (NIH); National Institute on Aging
[Z01-AG000949-02]; National Institute on Neurological Disorders and
Stroke (NINDS); Packard Centre for ALS Research at Hopkins; ALS
Association; Microsoft Research; Deutsche Forschungsgemeinschaft [SFB
581, TP B1]
FX Federazione Italiana Giuoco Calcio (Grant 2010 #1 to M.S. and A.C.);
Fondazione Vialli e Mauro per la Sclerosi Laterale Amiotrofica onlus (to
A.C.); Ministero della Salute (Ricerca Sanitaria Finalizzata, 2007) (to
A.C. and G.R.); European Community's Health Seventh Framework Programme
(FP7/2007-2013) under grant agreement 259867 (to A.C.); The Intramural
Research Programmes of the National Institutes of Health (NIH); National
Institute on Aging (Z01-AG000949-02); and National Institute on
Neurological Disorders and Stroke (NINDS); The Packard Centre for ALS
Research at Hopkins (to B.J.T.); the ALS Association (to B.J.T. and
A.C.); Microsoft Research (to B.J.T.); the Deutsche
Forschungsgemeinschaft (SFB 581 and TP B1 to C.D. and M.S.).
NR 25
TC 102
Z9 105
U1 3
U2 34
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 MAR
PY 2012
VL 135
BP 784
EP 793
DI 10.1093/brain/awr366
PN 3
PG 10
WC Clinical Neurology; Neurosciences
SC Neurosciences & Neurology
GA 898JI
UT WOS:000300738300011
PM 22366794
ER
PT J
AU Harford, JB
AF Harford, Joe B.
TI Viral infections and human cancers: the legacy of Denis Burkitt
SO BRITISH JOURNAL OF HAEMATOLOGY
LA English
DT Review
DE viral infections; human cancers; Burkitt lymphoma; Africa
ID EPSTEIN-BARR-VIRUS; HUMAN-IMMUNODEFICIENCY-VIRUS; HEPATITIS-C VIRUS;
T-CELL LEUKEMIA; HUMAN-PAPILLOMAVIRUS; HEPATOCELLULAR-CARCINOMA;
CERVICAL-CANCER; NASOPHARYNGEAL CARCINOMA; GEOGRAPHICAL-DISTRIBUTION;
PARTICLE VACCINE
AB Denis Parsons Burkitt was born in 1911, and in the late 1950s, described the disease that has come to be known as Burkitt lymphoma based on cases he observed in Uganda. Subsequently, Burkitt lymphoma was recognized as the first human tumour associated with an infectious agent when Epstein- Barr virus was isolated from samples supplied by Burkitt. It is now recognized that over one- quarter of cancers worldwide are tied to infections. Notably, liver cancer is linked to hepatitis B virus and hepatitis C virus infections, and cervical cancer to infections involving the human papilloma viruses. In addition, immunocompromise arising from infection with the human immunodeficiency virus allows tumours (e.g., Kaposi sarcoma) caused by other viruses to arise. More than 50 years after the seminal paper by Burkitt based on his work in Africa, it is appreciated that the contribution of viral infections to cancers remains considerably higher in sub- Saharan Africa than in the rest of the world.
C1 NCI, Bethesda, MD 20892 USA.
RP Harford, JB (reprint author), NCI, Bethesda, MD 20892 USA.
EM harfordj@nih.gov
NR 104
TC 4
Z9 4
U1 3
U2 12
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0007-1048
J9 BRIT J HAEMATOL
JI Br. J. Haematol.
PD MAR
PY 2012
VL 156
IS 6
BP 709
EP 718
DI 10.1111/j.1365-2141.2011.09017.x
PG 10
WC Hematology
SC Hematology
GA 901MY
UT WOS:000300972200004
PM 22233526
ER
PT J
AU Magrath, I
AF Magrath, Ian
TI Epidemiology: clues to the pathogenesis of Burkitt lymphoma
SO BRITISH JOURNAL OF HAEMATOLOGY
LA English
DT Review
DE epidemiology; Burkitt; lymphoma; malaria; Epstein-Barr
ID EPSTEIN-BARR-VIRUS; HUMAN-IMMUNODEFICIENCY-VIRUS; HEPATITIS-C VIRUS;
T-CELL LEUKEMIA; HUMAN-PAPILLOMAVIRUS; HEPATOCELLULAR-CARCINOMA;
CERVICAL-CANCER; NASOPHARYNGEAL CARCINOMA; GEOGRAPHICAL-DISTRIBUTION;
INFECTIOUS AGENTS
AB The two major epidemiological clues to the pathogenesis of Burkitt lymphoma (BL) are the geographical association with malaria - BL incidence relates to the malaria transmission rate - and early infection by Epstein- Barr virus (EBV). Both agents cause B cell hyperplasia, which is almost certainly an essential component of lymphomagenesis in BL. The critical event in lymphomagenesis is the creation of a MYC translocation, bringing the MYC gene into juxtaposition with immunoglobulin genes and causing its ectopic expression, thereby driving the proliferation of BL cells. It is highly likely that such translocations are mediated by the activation- induced cytidine deaminase (AID) gene, which is responsible for hypervariable region mutations as well as class switching. Stimulation of the Toll- like receptor 9 by malaria- associated agonists induces AID, providing a mechanism whereby malaria could directly influence BL pathogenesis. EBV- containing cells must reach the memory cell compartment in order to survive throughout the life of the individual, which probably requires traversal of the germinal centre. Normally, cells that do not produce high affinity antibodies do not survive this passage, and are induced to undergo apoptosis. EBV, however, prevents this, and in doing so may also enhance the likelihood of survival of rare translocation- containing cells.
C1 [Magrath, Ian] Int Network Canc Treatment & Res, B-1180 Brussels, Belgium.
[Magrath, Ian] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA.
[Magrath, Ian] NCI, Bethesda, MD 20892 USA.
RP Magrath, I (reprint author), Int Network Canc Treatment & Res, Rue Engeland 642, B-1180 Brussels, Belgium.
EM imagrath@inctr.be
NR 104
TC 37
Z9 40
U1 2
U2 10
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0007-1048
J9 BRIT J HAEMATOL
JI Br. J. Haematol.
PD MAR
PY 2012
VL 156
IS 6
BP 744
EP 756
DI 10.1111/j.1365-2141.2011.09013.x
PG 13
WC Hematology
SC Hematology
GA 901MY
UT WOS:000300972200007
PM 22260300
ER
PT J
AU Han, SS
Sue, LY
Berndt, SI
Selhub, J
Burdette, LA
Rosenberg, PS
Ziegler, RG
AF Han, Summer S.
Sue, Laura Y.
Berndt, Sonja I.
Selhub, Jacob
Burdette, Laurie A.
Rosenberg, Philip S.
Ziegler, Regina G.
TI Associations between Genes in the One-Carbon Metabolism Pathway and
Advanced Colorectal Adenoma Risk in Individuals with Low Folate Intake
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; METHYLENETETRAHYDROFOLATE REDUCTASE
POLYMORPHISM; ADENOSINE-DEAMINASE; CANCER-RISK; POLYPS; SURVEILLANCE;
GUIDELINE; TISSUES; SCAN
AB Background: Folate is essential for one-carbon metabolism, a pathway required by DNA synthesis, methylation, and repair. Low dietary and circulating folate and polymorphic variation in this pathway are associated with increased risk of colorectal adenoma and cancer.
Methods: We genotyped 882 single nucleotide polymorphisms (SNP) in 82 one-carbon metabolism genes for 1,331 cases of advanced colorectal adenoma, identified by sigmoidoscopy at baseline, and 1,501 controls from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO). We evaluated associations between one-carbon genes and adenoma risk in all subjects and stratified by folate intake. We applied the Adaptive Rank Truncated Product (ARTP) method to assess statistical significance at the gene and pathway levels.
Results: Folate intake was inversely associated with advanced colorectal adenoma risk [odds ratio (OR) by quartile = 0.85, P = 1.9 x 10(-5)]. We found no statistically significant associations between one-carbon genes and adenoma risk in all subjects. As hypothesized, we observed a statistically significant pathway-level association (P = 0.038) in the lowest quartile of folate; no significant associations were found in higher quartiles. Several genes including adenosine deaminase (ADA) and cysteine dioxygenase (CDO1) contributed to this signal (gene-level P = 0.001 and 0.0073, respectively). The most statistically significant SNP was rs244072 in ADA (P = 2.37 x 10(-5)).
Conclusions and Impact: Stratification by dietary folate and application of the ARTP method revealed statistically significant pathway-and gene-level associations between one-carbon metabolism genes and risk of advanced colorectal adenoma, which were not apparent in analysis of the entire population. Folate intake may interact with associations between common variants in one-carbon metabolism genes and colorectal adenoma risk. Cancer Epidemiol Biomarkers Prev; 21(3); 417-27. (C) 2012 AACR.
C1 [Han, Summer S.] NCI, Biostat Branch, Div Canc Epidemiol & Genet, Epidemiol & Biostat Program,NIH, Bethesda, MD 20892 USA.
[Selhub, Jacob] Tufts Univ, Jean Mayer USDA Human Nutr Res Ctr Aging, Boston, MA 02111 USA.
[Burdette, Laurie A.] NCI, Core Genotyping Facil, Adv Technol Ctr, Div Canc Epidemiol & Genet,NIH, Gaithersburg, MD USA.
RP Han, SS (reprint author), NCI, Biostat Branch, Div Canc Epidemiol & Genet, Epidemiol & Biostat Program,NIH, 6120 Execut Blvd,EPS 8089, Bethesda, MD 20892 USA.
EM summer.han@nih.gov
NR 39
TC 11
Z9 11
U1 0
U2 4
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1055-9965
J9 CANCER EPIDEM BIOMAR
JI Cancer Epidemiol. Biomarkers Prev.
PD MAR
PY 2012
VL 21
IS 3
BP 417
EP 427
DI 10.1158/1055-9965.EPI-11-0782
PG 11
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 905PG
UT WOS:000301284100005
PM 22253295
ER
PT J
AU Lindstrom, S
Schumacher, FR
Cox, D
Travis, RC
Albanes, D
Allen, NE
Andriole, G
Berndt, SI
Boeing, H
Bueno-de-Mesquita, HB
Crawford, ED
Diver, WR
Gaziano, JM
Giles, GG
Giovannucci, E
Gonzalez, CA
Henderson, B
Hunter, DJ
Johansson, M
Kolonel, LN
Ma, J
Le Marchand, L
Pala, V
Stampfer, M
Stram, DO
Thun, MJ
Tjonneland, A
Trichopoulos, D
Virtamo, J
Weinstein, SJ
Willett, WC
Yeager, M
Hayes, RB
Severi, G
Haiman, CA
Chanock, SJ
Peter, K
AF Lindstroem, Sara
Schumacher, Fredrick R.
Cox, David
Travis, Ruth C.
Albanes, Demetrius
Allen, Naomi E.
Andriole, Gerald
Berndt, Sonja I.
Boeing, Heiner
Bueno-de-Mesquita, H. Bas
Crawford, E. David
Diver, W. Ryan
Gaziano, J. Michael
Giles, Graham G.
Giovannucci, Edward
Gonzalez, Carlos A.
Henderson, Brian
Hunter, David J.
Johansson, Mattias
Kolonel, Laurence N.
Ma, Jing
Le Marchand, Loic
Pala, Valeria
Stampfer, Meir
Stram, Daniel O.
Thun, Michael J.
Tjonneland, Anne
Trichopoulos, Dimitrios
Virtamo, Jarmo
Weinstein, Stephanie J.
Willett, Walter C.
Yeager, Meredith
Hayes, Richard B.
Severi, Gianluca
Haiman, Christopher A.
Chanock, Stephen J.
Kraft, Peter
TI Common Genetic Variants in Prostate Cancer Risk Prediction-Results from
the NCI Breast and Prostate Cancer Cohort Consortium (BPC3)
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID GROWTH-FACTOR-I; BINDING PROTEIN-3; MARKER; RECLASSIFICATION;
SUSCEPTIBILITY; STATISTICS; PREVENTION; ANTIGEN; LUNG
AB Background: One of the goals of personalized medicine is to generate individual risk profiles that could identify individuals in the population that exhibit high risk. The discovery of more than two-dozen independent single-nucleotide polymorphism markers in prostate cancer has raised the possibility for such risk stratification. In this study, we evaluated the discriminative and predictive ability for prostate cancer risk models incorporating 25 common prostate cancer genetic markers, family history of prostate cancer, and age.
Methods: We fit a series of risk models and estimated their performance in 7,509 prostate cancer cases and 7,652 controls within the National Cancer Institute Breast and Prostate Cancer Cohort Consortium (BPC3). We also calculated absolute risks based on SEER incidence data.
Results: The best risk model (C-statistic = 0.642) included individual genetic markers and family history of prostate cancer. We observed a decreasing trend in discriminative ability with advancing age (P = 0.009), with highest accuracy in men younger than 60 years (C-statistic = 0.679). The absolute ten-year risk for 50-year-old men with a family history ranged from 1.6% (10th percentile of genetic risk) to 6.7% (90th percentile of genetic risk). For men without family history, the risk ranged from 0.8% (10th percentile) to 3.4% (90th percentile).
Conclusions: Our results indicate that incorporating genetic information and family history in prostate cancer risk models can be particularly useful for identifying younger men that might benefit from prostate-specific antigen screening.
Impact: Although adding genetic risk markers improves model performance, the clinical utility of these genetic risk models is limited. Cancer Epidemiol Biomarkers Prev; 21(3); 437-44. (C) 2012 AACR.
C1 [Kraft, Peter] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Dept Biostat, Boston, MA 02115 USA.
[Lindstroem, Sara; Hunter, David J.; Kraft, Peter] Harvard Univ, Sch Publ Hlth, Program Mol & Genet Epidemiol, Boston, MA 02115 USA.
[Giovannucci, Edward; Stampfer, Meir; Willett, Walter C.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Gaziano, J. Michael] Brigham & Womens Hosp, Div Aging, Dept Med, Boston, MA 02115 USA.
[Giovannucci, Edward; Hunter, David J.; Ma, Jing; Stampfer, Meir] Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA.
[Giovannucci, Edward; Hunter, David J.; Ma, Jing; Stampfer, Meir] Harvard Univ, Sch Med, Boston, MA 02115 USA.
[Gaziano, J. Michael] Boston Vet Affairs Healthcare Syst, Massachusetts Vet Epidemiol & Res Informat Ctr MA, Boston, MA USA.
[Gaziano, J. Michael] Boston Vet Affairs Healthcare Syst, Geriatr Res Educ & Clin Ctr GRECC, Boston, MA USA.
[Schumacher, Fredrick R.; Henderson, Brian; Stram, Daniel O.; Haiman, Christopher A.] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA 90033 USA.
[Cox, David] INSERM, U1052, Ctr Leon Berard, Canc Res Ctr Lyon, F-75654 Paris 13, France.
[Johansson, Mattias] Int Agcy Res Canc, Lyon, France.
[Cox, David] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Med, London SW7 2AZ, England.
[Cox, David] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Dept Epidemiol & Biostat, London SW7 2AZ, England.
[Travis, Ruth C.; Allen, Naomi E.] Univ Oxford, Nuffield Dept Clin Med, Canc Epidemiol Unit, Oxford, England.
[Albanes, Demetrius; Berndt, Sonja I.; Weinstein, Stephanie J.; Yeager, Meredith; Chanock, Stephen J.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Andriole, Gerald] Washington Univ, Sch Med, Div Urol Surg, St Louis, MO 63110 USA.
[Boeing, Heiner] Deutsch Inst Ernahrungsforsch, Dept Epidemiol, Potsdam, Germany.
[Bueno-de-Mesquita, H. Bas] Natl Inst Publ Hlth & Environm RIVM, Bilthoven, Netherlands.
[Bueno-de-Mesquita, H. Bas] Univ Med Ctr Utrecht UMCU, Dept Gastroenterol & Hepatol, Utrecht, Netherlands.
[Crawford, E. David] Univ Colorado, Hlth Sci Ctr, Denver, CO USA.
[Diver, W. Ryan; Thun, Michael J.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA.
[Giles, Graham G.; Severi, Gianluca] Univ Melbourne, Canc Epidemiol Ctr, Canc Council Victoria, Melbourne, Vic 3010, Australia.
[Giles, Graham G.; Severi, Gianluca] Univ Melbourne, Ctr Mol Genet Environm & Analyt Epidemiol, Melbourne, Vic 3010, Australia.
[Giles, Graham G.] Monash Univ, Dept Epidemiol & Prevent Med, Melbourne, Vic 3004, Australia.
[Gonzalez, Carlos A.] Catalan Inst Oncol IDIBELL RETICC RD06 0020, Unit Nutr Environm & Canc, Barcelona, Spain.
[Johansson, Mattias] Umea Univ, Dept Surg & Perioperat Sci, Umea, Sweden.
[Kolonel, Laurence N.; Le Marchand, Loic] Univ Hawaii, Program Epidemiol, Ctr Canc, Honolulu, HI 96822 USA.
[Pala, Valeria] Ist Nazl Tumori, Fdn IRCCS, Nutr Epidemiol Unit, Dept Predict Med, I-20133 Milan, Italy.
[Tjonneland, Anne] Danish Canc Soc, Inst Canc Epidemiol, Copenhagen, Denmark.
[Trichopoulos, Dimitrios] Acad Athens, Bur Epidemiol Res, Athens, Greece.
[Virtamo, Jarmo] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland.
[Hayes, Richard B.] NYU, Div Epidemiol, Langone Med Ctr, New York, NY USA.
RP Peter, K (reprint author), Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Dept Biostat, 655 Huntington Ave,Bldg 2,Room 207, Boston, MA 02115 USA.
EM pkraft@hsph.harvard.edu
RI Cox, David/A-2023-2009; Gonzalez, Carlos A/O-4651-2014; Albanes,
Demetrius/B-9749-2015;
OI Cox, David/0000-0002-2152-9259; Gonzalez, Carlos A/0000-0003-2822-9715;
Giles, Graham/0000-0003-4946-9099
FU U.S. NIH, National Cancer Institute (NIH/National Cancer Institute,
Division of Cancer Epidemiology and Genetics) [U01-CA98233-07,
U01-CA98710-06, U01-CA98216-06, U01-CA98758-07]
FX This work was supported by the U.S. NIH, National Cancer Institute
(cooperative agreements U01-CA98233-07 to D.J. Hunter, U01-CA98710-06 to
M.J. Thun, U01-CA98216-06 to E. Riboli and R. Kaaks, and U01-CA98758-07
to B. E. Henderson and Intramural Research Program of NIH/National
Cancer Institute, Division of Cancer Epidemiology and Genetics).
NR 37
TC 34
Z9 34
U1 0
U2 5
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1055-9965
J9 CANCER EPIDEM BIOMAR
JI Cancer Epidemiol. Biomarkers Prev.
PD MAR
PY 2012
VL 21
IS 3
BP 437
EP 444
DI 10.1158/1055-9965.EPI-11-1038
PG 8
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 905PG
UT WOS:000301284100007
PM 22237985
ER
PT J
AU Zheng, YL
Amr, S
Saleh, DA
Dash, C
Ezzat, S
Mikhail, NN
Gouda, I
Loay, I
Hifnawy, T
Abdel-Hamid, M
Khaled, H
Wolpert, B
Abdel-Aziz, MA
Loffredo, CA
AF Zheng, Yun-Ling
Amr, Sania
Saleh, Doa'a A.
Dash, Chiranjeev
Ezzat, Sameera
Mikhail, Nabiel N.
Gouda, Iman
Loay, Iman
Hifnawy, Tamer
Abdel-Hamid, Mohamed
Khaled, Hussein
Wolpert, Beverly
Abdel-Aziz, Mohamed A.
Loffredo, Christopher A.
TI Urinary Bladder Cancer Risk Factors in Egypt: A Multicenter Case-Control
Study
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID ENVIRONMENTAL TOBACCO-SMOKE; CIGARETTE-SMOKING; SCHISTOSOMIASIS;
EPIDEMIOLOGY; CARCINOMA; ALEXANDRIA; MECHANISMS; DISEASE; GENDER
AB Background: We investigated associations between tobacco exposure, history of schistosomiasis, and bladder cancer risk in Egypt.
Methods: We analyzed data from a case-control study (1,886 newly diagnosed and histologically confirmed cases and 2,716 age-, gender-, and residence-matched, population-based controls). Using logistic regression, we estimated the covariate-adjusted ORs and 95% confidence interval (CI) of the associations.
Results: Among men, cigarette smoking was associated with an increased risk of urothelial carcinoma (OR = 1.8; 95% CI, 1.4-2.2) but not squamous cell carcinoma (SCC); smoking both water pipes and cigarettes was associated with an even greater risk for urothelial carcinoma (OR = 2.9; 95% CI, 2.1-3.9) and a statistically significant risk for SCC (OR = 1.8; 95% CI, 1.2-2.6). Among nonsmoking men and women, environmental tobacco smoke exposure was associated with an increased risk of urothelial carcinoma. History of schistosomiasis was associated with increased risk of both urothelial carcinoma (OR = 1.9; 95% CI, 1.2-2.9) and SCC (OR = 1.9; 95% CI, 1.2-3.0) in women and to a lesser extent (OR = 1.4; 95% CI, 1.2-1.7 and OR = 1.4; 95% CI, 1.1-1.7, for urothelial carcinoma and SCC, respectively) in men.
Conclusions: The results suggest that schistosomiasis and tobacco smoking increase the risk of both SCC and urothelial carcinoma.
Impact: This study provides new evidence for associations between bladder cancer subtypes and schistosomiasis and suggests that smoking both cigarettes and water pipes increases the risk for SCC and urothelial carcinoma in Egyptian men. Cancer Epidemiol Biomarkers Prev; 21(3); 537-46. (C) 2011 AACR.
C1 [Zheng, Yun-Ling; Dash, Chiranjeev; Loffredo, Christopher A.] Georgetown Univ, Lombardi Comprehens Canc Ctr, Carcinogenesis Biomarkers & Epidemiol Program, Washington, DC 20057 USA.
[Amr, Sania; Wolpert, Beverly] Univ Maryland, Sch Med, Dept Epidemiol & Publ Hlth, Baltimore, MD 21201 USA.
[Saleh, Doa'a A.] Cairo Univ, Dept Community Med, Cairo, Egypt.
[Gouda, Iman; Loay, Iman; Khaled, Hussein] Natl Canc Inst, Bethesda, MD 20892 USA.
[Abdel-Hamid, Mohamed] Menia Univ, Dept Microbiol, Cairo, Egypt.
[Abdel-Hamid, Mohamed] Natl Hepatol & Trop Med Res Inst, Cairo, Egypt.
[Ezzat, Sameera] Menoufiya Univ, Natl Liver Inst, Shibin Al Kawm, Egypt.
[Mikhail, Nabiel N.; Abdel-Aziz, Mohamed A.] Assiut Univ, S Egypt Canc Inst, Assiut, Egypt.
[Hifnawy, Tamer] Beni Suif Univ, Dept Publ Hlth, Beni Suif, Egypt.
RP Loffredo, CA (reprint author), Georgetown Univ, Lombardi Comprehens Canc Ctr, Carcinogenesis Biomarkers & Epidemiol Program, 3800 Reservoir Rd NW,LL Room 153, Washington, DC 20057 USA.
EM cal9@georgetown.edu
FU Ministry of Health and Population of Egypt; Cancer Center in Cairo;
Cancer Center in Minia; Cancer Center in Assiut; National Cancer
Institute of the U.S. NIH [R01-CA115618, R01-CA132996]
FX The authors thank the Ministry of Health and Population of Egypt and the
Cancer Centers in Cairo, Minia, and Assiut for supporting the study. We
are also indebted to the many interviewers, translators, drivers, and
other support personnel who made the study possible through their
dedicated work. The greatest gratitude goes to all the individuals who
participated in our study.; This work was supported by grants from the
National Cancer Institute of the U.S. NIH (R01-CA115618 to C.A. Loffredo
and R01-CA132996 to Y.-L. Zheng).
NR 36
TC 21
Z9 21
U1 1
U2 7
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1055-9965
J9 CANCER EPIDEM BIOMAR
JI Cancer Epidemiol. Biomarkers Prev.
PD MAR
PY 2012
VL 21
IS 3
BP 537
EP 546
DI 10.1158/1055-9965.EPI-11-0589
PG 10
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 905PG
UT WOS:000301284100019
PM 22147365
ER
PT J
AU Hou, NQ
Zheng, YL
Gamazon, ER
Ogundiran, TO
Adebamowo, C
Nathanson, KL
Domchek, SM
Rebbeck, TR
Simon, MS
John, EM
Hennis, A
Nemesure, B
Wu, SY
Leske, MC
Ambs, S
Niu, Q
Zhang, J
Pierce, B
Cox, NJ
Olopade, OI
Huo, DZ
AF Hou, Ningqi
Zheng, Yonglan
Gamazon, Eric R.
Ogundiran, Temidayo O.
Adebamowo, Clement
Nathanson, Katherine L.
Domchek, Susan M.
Rebbeck, Timothy R.
Simon, Michael S.
John, Esther M.
Hennis, Anselm
Nemesure, Barbara
Wu, Suh-Yuh
Leske, M. Cristina
Ambs, Stefan
Niu, Qun
Zhang, Jing
Pierce, Brandon
Cox, Nancy J.
Olopade, Olufunmilayo I.
Huo, Dezheng
TI Genetic Susceptibility to Type 2 Diabetes and Breast Cancer Risk in
Women of European and African Ancestry
SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; OBESITY
AB Background: Epidemiologic studies have reported a positive association between type 2 diabetes (T2D) and breast cancer risk, independent of body weight.
Methods: We investigated 40 genetic variants known to be associated with T2D in relation to breast cancer risk among 2,651 breast cancer cases and 2,520 controls of African or European ancestry that were pooled from seven studies.
Results: We found that two T2D risk alleles in Caucasian women (rs5945326-G, rs12518099-C) and one in women of African ancestry (rs7578597-T) were positively associated with breast cancer risk at a nominal significance level of 0.05, whereas two T2D risk alleles were inversely associated with breast cancer risk in Caucasian women (rs1111875-C, rs10923931-T). The composite T2D susceptibility score (the number of risk allele) was not significantly associated with breast cancer risk.
Conclusion: The association between established T2D genetic susceptibility variants and breast cancer risk in women of African or European ancestry is likely weak, if it does exist.
Impact: The pleiotropic effects of known T2D risk alleles cannot explain the association between T2D and breast cancer risk. Cancer Epidemiol Biomarkers Prev; 21(3); 552-6. (C) 2012 AACR.
C1 [Hou, Ningqi; Pierce, Brandon; Huo, Dezheng] Univ Chicago, Dept Hlth Studies, Chicago, IL 60637 USA.
[Zheng, Yonglan; Gamazon, Eric R.; Niu, Qun; Zhang, Jing; Cox, Nancy J.; Olopade, Olufunmilayo I.] Univ Chicago, Dept Med, Chicago, IL 60637 USA.
[Ogundiran, Temidayo O.] Univ Ibadan, Dept Surg, Coll Med, Ibadan, Nigeria.
[Adebamowo, Clement] Univ Maryland, Dept Epidemiol & Prevent Med, Baltimore, MD 21201 USA.
[Nathanson, Katherine L.; Domchek, Susan M.] Univ Penn, Dept Med, Philadelphia, PA 19104 USA.
[Rebbeck, Timothy R.] Univ Penn, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA.
[Simon, Michael S.] Wayne State Univ, Dept Oncol, Karmanos Canc Inst, Detroit, MI USA.
[John, Esther M.] Stanford Univ, Sch Med, Dept Hlth Res & Policy, Stanford, CA 94305 USA.
[John, Esther M.] Stanford Canc Inst, Stanford, CA USA.
[Hennis, Anselm] Univ W Indies, Chron Dis Res Ctr, Bridgetown, Barbados.
[Hennis, Anselm] Univ W Indies, Res Inst Trop Med, Bridgetown, Barbados.
[Nemesure, Barbara; Wu, Suh-Yuh; Leske, M. Cristina] SUNY Stony Brook, Dept Prevent Med, Stony Brook, NY 11794 USA.
[Ambs, Stefan] NCI, Human Carcinogenesis Lab, Bethesda, MD 20892 USA.
RP Huo, DZ (reprint author), Univ Chicago, Dept Hlth Studies, 5841 S Maryland Ave,MC 2007, Chicago, IL 60637 USA.
EM dhuo@health.bsd.uchicago.edu
OI Adebamowo, Clement/0000-0002-6571-2880; Nathanson,
Katherine/0000-0002-6740-0901; Pierce, Brandon/0000-0002-7829-952X;
Gamazon, Eric/0000-0003-4204-8734
FU National Cancer Institute (NCI) [R01CA141712, P01CA82707]; Breast Cancer
Research Foundation; U.S. NCI, NIH [RFA-CA-06-503]; BCFR; Northern
California Cancer Center [U01CA69417]; Georgetown University Medical
Center Informatics Support Center [HHSN261200900010C]
FX This work was supported by National Cancer Institute (NCI) grant
R01CA141712 and P01CA82707; support also was given by the Breast Cancer
Research Foundation. The Northern California site of the Breast Cancer
Family Registry (BCFR) was supported by the U.S. NCI, NIH under
RFA-CA-06-503 and through cooperative agreements with members of the
BCFR and Principal Investigators, including the Northern California
Cancer Center (U01CA69417) and Georgetown University Medical Center
Informatics Support Center (HHSN261200900010C).
NR 10
TC 3
Z9 3
U1 0
U2 2
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1055-9965
J9 CANCER EPIDEM BIOMAR
JI Cancer Epidemiol. Biomarkers Prev.
PD MAR
PY 2012
VL 21
IS 3
BP 552
EP 556
DI 10.1158/1055-9965.EPI-11-0979
PG 5
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 905PG
UT WOS:000301284100021
PM 22237986
ER
PT J
AU Dewdney, SB
Kizer, NT
Andaya, AA
Babb, SA
Luo, JQ
Mutch, DG
Schmidt, AP
Brinton, LA
Broaddus, RR
Ramirez, NC
Huettner, PC
McMeekin, DS
Darcy, K
Ali, S
Judson, PL
Mannel, RS
Lele, SB
O'Malley, DM
Goodfellow, PJ
AF Dewdney, Summer B.
Kizer, Nora T.
Andaya, Abegail A.
Babb, Sheri A.
Luo, Jingqin
Mutch, David G.
Schmidt, Amy P.
Brinton, Louise A.
Broaddus, Russell R.
Ramirez, Nilsa C.
Huettner, Phyllis C.
McMeekin, Donald Scott
Darcy, Kathleen
Ali, Shamshad
Judson, Patricia L.
Mannel, Robert S.
Lele, Shashikant B.
O'Malley, David M.
Goodfellow, Paul J.
TI Uterine Serous Carcinoma: Increased Familial Risk for Lynch-Associated
Malignancies
SO CANCER PREVENTION RESEARCH
LA English
DT Article
ID NONPOLYPOSIS COLORECTAL-CANCER; ENDOMETRIAL CANCER; PANCREATIC-CANCER;
PAPILLARY CARCINOMA; GERMLINE MUTATIONS; BRCA2 MUTATIONS; BREAST-CANCER;
HER-2/NEU OVEREXPRESSION; JEWISH PATIENTS; WOMEN
AB Serous uterine cancer is not a feature of any known hereditary cancer syndrome. This study evaluated familial risk of cancers for patients with serous uterine carcinoma, focusing on Lynch syndrome malignancies. Fifty serous or mixed serous endometrial carcinoma cases were prospectively enrolled. Pedigrees were developed for 29 probands and tumors were assessed for DNA mismatch repair (MMR) abnormalities. Standardized incidence ratios for cancers in relatives were estimated. A second-stage analysis was undertaken using data from Gynecologic Oncology Group (GOG)-210. Incidence data for cancers reported in relatives of 348 patients with serous and mixed epithelial and 624 patients with endometrioid carcinoma were compared. Nineteen of 29 (65.5%) patients in the single-institution series reported a Lynch-related cancer in relatives. Endometrial and ovarian cancers were significantly overrepresented and a high number of probands (6 of 29, 20.7%) reported pancreatic cancers. None of the probands' tumors had DNA MMR abnormalities. There was no difference in endometrial or ovarian cancer incidence in relatives of serous and endometrioid cancer probands in the case-control study. Pancreatic cancers were, however, significantly more common in relatives of patients with serous cancer [OR, 2.39; 95% confidence interval (CI), 1.06-5.38]. We identified an excess of endometrial, ovarian, and pancreatic cancers in relatives of patients with serous cancer in a single-institution study. Follow-up studies suggest that only pancreatic cancers are overrepresented in relatives. DNA MMR defects in familial clustering of pancreatic and other Lynch-associated malignancies are unlikely. The excess of pancreatic cancers in relatives may reflect an as yet unidentified hereditary syndrome that includes uterine serous cancers. Cancer Prev Res; 5(3); 435-43. (C) 2012 AACR.
C1 [Schmidt, Amy P.; Goodfellow, Paul J.] Washington Univ, Sch Med, Dept Surg, St Louis, MO 63110 USA.
[Dewdney, Summer B.; Kizer, Nora T.; Babb, Sheri A.; Mutch, David G.; Goodfellow, Paul J.] Washington Univ, Sch Med, Dept Obstet & Gynecol, St Louis, MO 63110 USA.
[Huettner, Phyllis C.] Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA.
[Luo, Jingqin] Washington Univ, Sch Med, Div Biostat, St Louis, MO 63110 USA.
[Andaya, Abegail A.; Brinton, Louise A.] NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA.
[Broaddus, Russell R.] Univ Texas MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA.
[Ramirez, Nilsa C.] Nationwide Childrens Hosp, Res Inst, Dept Pathol & Lab Med, Columbus, OH USA.
[O'Malley, David M.] Ohio State Univ, Dept Obstet & Gynecol, Columbus, OH 43210 USA.
[O'Malley, David M.] James Graham Brown Canc Ctr, Columbus, OH USA.
[McMeekin, Donald Scott; Mannel, Robert S.] Univ Oklahoma, Hlth Sci Ctr, Dept Obstet & Gynecol, Oklahoma City, OK 73190 USA.
[Darcy, Kathleen; Ali, Shamshad] Roswell Pk Canc Inst, Gynecol Oncol Grp, Stat & Data Ctr, Buffalo, NY 14263 USA.
[Lele, Shashikant B.] Roswell Pk Canc Inst, Dept Gynecol, Buffalo, NY 14263 USA.
[Judson, Patricia L.] Univ Minnesota, Sch Med, Dept Obstet Gynecol & Womens Hlth, Minneapolis, MN 55455 USA.
RP Goodfellow, PJ (reprint author), Washington Univ, Sch Med, Dept Surg, 660 S Euclid,Box 8109, St Louis, MO 63110 USA.
EM goodfellowp@wudosis.wustl.edu
RI OMalley, David/E-3789-2011; Brinton, Louise/G-7486-2015
OI Brinton, Louise/0000-0003-3853-8562
FU National Cancer Institute [CA134254]; Gynecologic Oncology Group (GOG)
Administrative Office [CA 27469]; Gynecologic Oncology Group Statistical
Office [CA 37517]; GOG Cooperative Group [U10CA027469]; [CA071754]
FX This study was supported by a National Cancer Institute P50 SPORE PJG
award (CA134254), grants to the Gynecologic Oncology Group (GOG)
Administrative Office (CA 27469) and the Gynecologic Oncology Group
Statistical Office (CA 37517), the GOG Cooperative Group (U10CA027469),
and RO1 funding to P.J. Goodfellow (CA071754).
NR 50
TC 4
Z9 4
U1 0
U2 1
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1940-6207
J9 CANCER PREV RES
JI Cancer Prev. Res.
PD MAR
PY 2012
VL 5
IS 3
BP 435
EP 443
DI 10.1158/1940-6207.CAPR-11-0499
PG 9
WC Oncology
SC Oncology
GA 901ST
UT WOS:000300987800010
PM 22246618
ER
PT J
AU Adoro, S
Park, JH
Singer, A
AF Adoro, Stanley
Park, Jung-Hyun
Singer, Alfred
TI Coreceptor gene "imprinting" A genetic solution to a developmental
dilemma in T cells
SO CELL CYCLE
LA English
DT Editorial Material
ID LINEAGE COMMITMENT; DIFFERENTIATION; CD8; THYMOCYTES; SELECTION; CHOICE
C1 [Adoro, Stanley; Park, Jung-Hyun; Singer, Alfred] NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA.
RP Singer, A (reprint author), NCI, Expt Immunol Branch, NIH, Bldg 10, Bethesda, MD 20892 USA.
EM singera@mail.nih.gov
RI Park, Jung Hyun /B-5712-2015
OI Park, Jung Hyun /0000-0002-9547-9055
NR 11
TC 3
Z9 3
U1 0
U2 0
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 1538-4101
J9 CELL CYCLE
JI Cell Cycle
PD MAR 1
PY 2012
VL 11
IS 5
BP 833
EP 834
DI 10.4161/cc.11.5.19596
PG 2
WC Cell Biology
SC Cell Biology
GA 901TM
UT WOS:000300989700004
PM 22333594
ER
PT J
AU Pobezinskaya, YL
Liu, ZG
AF Pobezinskaya, Yelena L.
Liu, Zhenggang
TI The role of TRADD in death receptor signaling
SO CELL CYCLE
LA English
DT Article
DE death receptor; TRADD; apoptosis; necrosis; MAP kinase
ID TUMOR-NECROSIS-FACTOR; NF-KAPPA-B; DOMAIN-CONTAINING RECEPTOR; TNF-LIKE
LIGAND; APOPTOSIS-MEDIATING RECEPTOR; PEYERS PATCH ORGANOGENESIS; P75
NEUROTROPHIN RECEPTOR; FADD-DEPENDENT APOPTOSIS; T-CELL PROLIFERATION;
TOLL-LIKE-RECEPTORS
AB TRADD (TNFR1-associated death domain protein) was initially identified as an adaptor molecule that transduces the signal downstream of the TNFR1 (tumor necrosis factor receptor 1). TNFR1 belongs to the so-called death receptor (DR) family of receptors that, depending on the context, can induce either apoptosis or proliferation, as well as NF kappa B and MAP kinase activation. The receptors of this group contain death domain (DD), which is necessary for the induction of apoptosis. This review summarizes the recent advances in the field of DR signaling and in particular the role of TRADD.
C1 [Pobezinskaya, Yelena L.; Liu, Zhenggang] NCI, Cell & Canc Biol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Liu, ZG (reprint author), NCI, Cell & Canc Biol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
EM zgliu@helix.nih.gov
NR 83
TC 20
Z9 21
U1 0
U2 6
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 1538-4101
J9 CELL CYCLE
JI Cell Cycle
PD MAR 1
PY 2012
VL 11
IS 5
BP 871
EP 876
DI 10.4161/cc.11.5.19300
PG 6
WC Cell Biology
SC Cell Biology
GA 901TM
UT WOS:000300989700016
PM 22333735
ER
PT J
AU Murphy, RF
Komlodi-Pasztor, E
Robey, R
Balis, FM
Farrell, NP
Fojo, T
AF Murphy, Robert F.
Komlodi-Pasztor, Edina
Robey, Rob
Balis, Frank M.
Farrell, Nicholas P.
Fojo, Tito
TI Retained platinum uptake and indifference to p53 status make novel
transplatinum agents active in platinum-resistant cells compared with
cisplatin and oxaliplatin
SO CELL CYCLE
LA English
DT Article
DE transplatinum compounds; drug resistance; p53; cell cycle; apoptosis;
DNA platination; platinum uptake
ID ANTICANCER DRUG SCREEN; OVARIAN-CANCER CELLS; CELLULAR ACCUMULATION;
COLORECTAL-CANCER; AMINE COMPLEXES; MOLECULAR-BASIS; LUNG-CANCER; DONOR
SETS; PHASE-II; CYTOTOXICITY
AB Despite the clinical success of platinum-containing drugs in the treatment of solid tumors, acquired resistance remains a major obstacle. We previously identified a group of novel transplanaramine or transplatinum compounds based on distinct activity profiles in the NCI-60 panel. In the present study, parental KB-3.1 cells with wild-type p53 and its cisplatin-and oxaliplatin-resistant sublines harboring mutant p53 proteins were used to contrast several transplatinum compounds with cisplatin and oxaliplatin. The transplatinum compounds retained cytotoxic activity in the resistant cell lines. While intracellular accumulation and DNA platination of cisplatin and oxaliplatin was decreased in the resistant cells, the transplatinum compounds both accumulated intracellularly and platinated DNA at comparable levels in all cell lines. Cytoflow analysis confirmed that cisplatin and oxaliplatin alter the cell cycle distribution and result in apoptosis; however, at comparably toxic concentrations, the transplatinum compounds did not alter the cell cycle distribution. Analysis of the cytoplasmic fraction treated with acetone showed that cisplatin and oxaliplatin readily bound to macromolecules in the pellet, whereas a larger percentage of the transplatinum compounds remained in the supernatant. We concluded that, distinct from platinum compounds currently in use, transplatinum compounds accumulate intracellularly in resistant cells at levels comparable to those in drug-sensitive cells, do not affect the cell cycle and, thus, retain cytotoxicity independent of p53 status and likely have cytoplasmic targets that are important in their activity.
C1 [Murphy, Robert F.] NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Komlodi-Pasztor, Edina; Robey, Rob; Fojo, Tito] NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Balis, Frank M.] Childrens Hosp Philadelphia, Ctr Childhood Canc Res, Philadelphia, PA 19104 USA.
[Farrell, Nicholas P.] Virginia Commonwealth Univ, Dept Chem, Richmond, VA 23284 USA.
RP Murphy, RF (reprint author), NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA.
EM murphyb@mail.nih.gov; fojot@mail.nih.gov
NR 51
TC 9
Z9 9
U1 1
U2 7
PU LANDES BIOSCIENCE
PI AUSTIN
PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA
SN 1538-4101
J9 CELL CYCLE
JI Cell Cycle
PD MAR 1
PY 2012
VL 11
IS 5
BP 963
EP 973
DI 10.4161/cc.11.5.19447
PG 11
WC Cell Biology
SC Cell Biology
GA 901TM
UT WOS:000300989700025
PM 22333583
ER
PT J
AU Bagci, U
Bray, M
Caban, J
Yao, JH
Mollura, DJ
AF Bagci, Ulas
Bray, Mike
Caban, Jesus
Yao, Jianhua
Mollura, Daniel J.
TI Computer-assisted detection of infectious lung diseases: A review (vol
36, pg 72, 2012)
SO COMPUTERIZED MEDICAL IMAGING AND GRAPHICS
LA English
DT Correction
C1 [Bagci, Ulas; Mollura, Daniel J.] NIH, Ctr Infect Dis Imaging, Dept Radiol & Imaging Sci, Bethesda, MD 20892 USA.
[Bray, Mike] NIAID, NIH, Bethesda, MD 20892 USA.
[Caban, Jesus] NIH, Natl Lib Med, Bethesda, MD 20892 USA.
RP Bagci, U (reprint author), NIH, Ctr Infect Dis Imaging, Dept Radiol & Imaging Sci, Bethesda, MD 20892 USA.
EM ulasbagci@gmail.com
RI Bagci, Ulas/A-4225-2012;
OI Bagci, Ulas/0000-0001-7379-6829
NR 1
TC 0
Z9 0
U1 0
U2 3
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0895-6111
J9 COMPUT MED IMAG GRAP
JI Comput. Med. Imaging Graph.
PD MAR
PY 2012
VL 36
IS 2
BP 169
EP 169
DI 10.1016/j.compmedimag.2011.12.003
PG 1
WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging
SC Engineering; Radiology, Nuclear Medicine & Medical Imaging
GA 902KA
UT WOS:000301035800008
ER
PT J
AU Peters-Lawrence, MH
Bell, MC
Hsu, LL
Osunkwo, I
Seaman, P
Blackwood, M
Guillaume, E
Bellevue, R
Krishnamurti, L
Smith, WR
Dampier, CD
Minniti, CP
AF Peters-Lawrence, Marlene H.
Bell, Margaret C.
Hsu, Lewis L.
Osunkwo, Ifeyinwa
Seaman, Phillip
Blackwood, Miren
Guillaume, Edouard
Bellevue, Rita
Krishnamurti, Lakshmanan
Smith, Wally R.
Dampier, Carlton D.
Minniti, Caterina P.
CA SCDCRN
TI Clinical trial implementation and recruitment: Lessons learned from the
early closure of a randomized clinical trial
SO CONTEMPORARY CLINICAL TRIALS
LA English
DT Article
DE Recruitment; Clinical trial; Sickle cell disease; Minority; Pain;
Protocol development
ID RESEARCH PARTICIPATION; STRATEGIES; PAIN
AB Background: The NHLBI-sponsored Sickle Cell Disease Clinical Research Network (SCDCRN) conducted a multi-center, acute intervention randomized clinical trial of two methods of Patient Controlled Analgesia for acute pain. This trial was terminated early due to low enrollment. We analyzed the perceived barriers and recruitment difficulties as reported by the coordinators and principal investigators.
Methods: Participating sites completed a missed eligibility log of subjects admitted in pain crisis throughout the study and a survey at the end of the trial. The survey covered site-specific factors, policies, and procedures in study implementation, recruitment strategies, and eligibility factors. The New England Research Institutes (NERI) collected de-identified surveys from 31 respondents at 29 of 31 participating sites.
Results: From December 2009 to June 2010, 1116 patient encounters for SCD and pain occurred at participating institutions: 38 subjects were enrolled (14 pediatric and 24 adults) and 34 completed the trial, below the projected 278 subjects. Fourteen sites enrolled subjects and seventeen did not. Recruitment barriers included insufficient staff, subject ineligibility or in too much pain to consent, competing protocols, and concerns regarding pain control. Recruitment methods were referrals from urgent care. SCD clinics and in house databases. No use of media or outside physicians was reported.
Conclusion: We identified multiple barriers to patient accrual including short duration of enrollment period, protocol design, complex dosing schedule, requirement for staff availability during week-end and after hours, multiple departments' involvement, protocol acceptance, eligibility criteria, competing protocols, and limited staff. Each of these areas should be targeted for intervention in order to plan and conduct successful future clinical trials. Published by Elsevier Inc.
C1 [Peters-Lawrence, Marlene H.; Minniti, Caterina P.] NIH, Cardiovasc & Pulm Med Branch, Bethesda, MD 20892 USA.
[Bell, Margaret C.] New England Res Inst, Watertown, MA 02172 USA.
[Hsu, Lewis L.] Childrens Natl Med Ctr, Washington, DC 20010 USA.
[Osunkwo, Ifeyinwa] Emory Univ, Sch Med, Aflac Canc Ctr, Atlanta, GA USA.
[Osunkwo, Ifeyinwa] Emory Univ, Sch Med, Blood Disorders Serv, Atlanta, GA USA.
[Osunkwo, Ifeyinwa; Dampier, Carlton D.] Childrens Healthcare Atlanta, Atlanta, GA USA.
[Seaman, Phillip] Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
[Blackwood, Miren; Guillaume, Edouard] Interfaith Med Ctr, Brooklyn, NY USA.
[Bellevue, Rita] New York Methodist Hosp, Dept Med, New York, NY USA.
[Krishnamurti, Lakshmanan] Childrens Hosp Pittsburgh, Pittsburgh, PA 15213 USA.
[Smith, Wally R.] Virginia Commonwealth Univ, Dept Internal Med, Richmond, VA USA.
RP Minniti, CP (reprint author), NHLBI, NIH, Cardiovasc & Pulm Branch, Bldg 10CRC Room 5-5140, Bethesda, MD 20892 USA.
EM minnitic@nhlbi.nih.gov
FU National Heart, Lung, and Blood Institute, National Institutes of Health
[U10HL083721, M01-RR02172, ULl-RR-024134, U54 RR026076, UL1RR031988,
UL1RR025747]
FX This publication was made possible by Grant Number U10HL083721,
M01-RR02172, ULl-RR-024134, U54 RR026076, UL1RR031988, UL1RR025747, and
intramural funding from the National Heart, Lung, and Blood Institute,
National Institutes of Health. Its contents are solely the
responsibility of the authors and do not necessarily represent the
official views of the National Institutes of Health.
NR 16
TC 24
Z9 24
U1 0
U2 3
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1551-7144
J9 CONTEMP CLIN TRIALS
JI Contemp. Clin. Trials
PD MAR
PY 2012
VL 33
IS 2
BP 291
EP 297
DI 10.1016/j.cct.2011.11.018
PG 7
WC Medicine, Research & Experimental; Pharmacology & Pharmacy
SC Research & Experimental Medicine; Pharmacology & Pharmacy
GA 901JA
UT WOS:000300962000007
PM 22155024
ER
PT J
AU Campbell, ANC
Nunes, EV
Miele, GM
Matthews, A
Polsky, D
Ghitza, UE
Turrigiano, E
Bailey, GL
VanVeldhuisen, P
Chapdelaine, R
Froias, A
Stitzer, ML
Carroll, KM
Winhusen, T
Clingerman, S
Perez, L
McClure, E
Goldman, B
Crowell, AR
AF Campbell, Aimee N. C.
Nunes, Edward V.
Miele, Gloria M.
Matthews, Abigail
Polsky, Daniel
Ghitza, Udi E.
Turrigiano, Eva
Bailey, Genie L.
VanVeldhuisen, Paul
Chapdelaine, Rita
Froias, Autumn
Stitzer, Maxine L.
Carroll, Kathleen M.
Winhusen, Theresa
Clingerman, Sara
Perez, Livangelie
McClure, Erin
Goldman, Bruce
Crowell, A. Rebecca
TI Design and methodological considerations of an effectiveness trial of a
computer-assisted intervention: An example from the NIDA Clinical Trials
Network
SO CONTEMPORARY CLINICAL TRIALS
LA English
DT Article
DE Substance use disorders; Computer-assisted treatment; Effectiveness
research; Clinical trial design; Randomized trials
ID COGNITIVE-BEHAVIORAL THERAPY; RANDOMIZED CONTROLLED-TRIAL;
COMMUNITY-REINFORCEMENT APPROACH; WEB-BASED INTERVENTIONS; SUBSTANCE USE
DISORDERS; COCAINE DEPENDENCE; MOTIVATIONAL INCENTIVES; ADDICTION
TREATMENT; METAANALYSIS; ANXIETY
AB Computer-assisted interventions hold the promise of minimizing two problems that are ubiquitous in substance abuse treatment: the lack of ready access to treatment and the challenges to providing empirically-supported treatments. Reviews of research on computer-assisted treatments for mental health and substance abuse report promising findings, but study quality and methodological limitations remain an issue. In addition, relatively few computer-assisted treatments have been tested among illicit substance users. This manuscript describes the methodological considerations of a multi-site effectiveness trial conducted within the National Institute on Drug Abuse's (NIDA's) National Drug Abuse Treatment Clinical Trials Network (CTN). The study is evaluating a web-based version of the Community Reinforcement Approach, in addition to prize-based contingency management, among 500 participants enrolled in 10 outpatient substance abuse treatment programs. Several potential effectiveness trial designs were considered and the rationale for the choice of design in this study is described. The study uses a randomized controlled design (with independent treatment arm allocation), intention-to-treat primary outcome analysis, biological markers for the primary outcome of abstinence, long-term follow-up assessments, precise measurement of intervention dose, and a cost-effectiveness analysis. Input from community providers during protocol development highlighted potential concerns and helped to address issues of practicality and feasibility. Collaboration between providers and investigators supports the utility of infrastructures that enhance research partnerships to facilitate effectiveness trials and dissemination of promising, technologically innovative treatments. Outcomes from this study will further the empirical knowledge base on the effectiveness and cost-effectiveness of computer-assisted treatment in clinical treatment settings. (C) 2011 Elsevier Inc. All rights reserved.
C1 [Campbell, Aimee N. C.; Nunes, Edward V.; Miele, Gloria M.] Columbia Univ Coll Phys & Surg, New York State Psychiat Inst, Dept Psychiat, New York, NY 10032 USA.
[Matthews, Abigail; VanVeldhuisen, Paul] EMMES Corp, Rockville, MD 20850 USA.
[Polsky, Daniel] Univ Penn, Sch Med, Philadelphia, PA 19104 USA.
[Ghitza, Udi E.] NIDR, Ctr Clin Trials Network, Bethesda, MD 20892 USA.
[Bailey, Genie L.; Chapdelaine, Rita; Froias, Autumn] Stanley St Treatment & Resources Inc, Fall River, MA 02720 USA.
[Bailey, Genie L.] Brown Univ, Warren Alpert Med Sch, Providence, RI 02912 USA.
[Stitzer, Maxine L.; McClure, Erin] Johns Hopkins Univ, Sch Med, Baltimore, MD 21224 USA.
[Carroll, Kathleen M.] Yale Univ, Sch Med, West Haven, CT 06516 USA.
[Winhusen, Theresa] Univ Cincinnati, Dept Psychiat, Cincinnati, OH 45220 USA.
[Clingerman, Sara; Perez, Livangelie] Ctr Drug Free Living Inc, Orlando, FL 32806 USA.
[Goldman, Bruce] N Shore Long Isl Jewish Hlth Syst, Hempstead, NY 11552 USA.
[Crowell, A. Rebecca] Nexus Recovery Inc, Dallas, TX 75228 USA.
RP Campbell, ANC (reprint author), Columbia Univ Coll Phys & Surg, New York State Psychiat Inst, Dept Psychiat, 1051 Riverside Dr,Unit 120,Room 3732, New York, NY 10032 USA.
EM anc2002@columbia.edu
OI Winhusen, Theresa/0000-0002-3364-0739; Carroll,
Kathleen/0000-0003-3263-3374
FU National Drug Abuse Treatment Clinical Trials Network (CTN), National
Institute on Drug Abuse (NIDA) [U10 DA13035, U10 DA015831, U10 DA013034,
U10 DA013732, U10 DA013720, K24 DA022412]; Titan Pharmaceuticals, Inc.;
Alkermes, Inc.
FX This work was supported by grants from the National Drug Abuse Treatment
Clinical Trials Network (CTN), National Institute on Drug Abuse (NIDA):
U10 DA13035 (Edward V. Nunes and John Rotrosen), U10 DA015831 (Kathleen
M. Carroll and Roger D. Weiss), U10 DA013034 (Maxine L Stitzer and
Robert P. Schwartz), U10 DA013732 (Eugene C. Somoza), U10 DA013720 (Jose
Szapocznik and Lisa R. Metsch), and K24 DA022412 (Edward V. Nunes).
Staff from NIDA's Center for the Clinical Trials Network collaborated in
the design of the study, contributed to writing this manuscript, and
provided editorial comments.; Dr. Genie Bailey has been on the speaker's
bureau of Forest Pharmaceuticals and Pfizer and has received research
support from Titan Pharmaceuticals, Inc. and Alkermes, Inc.
NR 49
TC 23
Z9 23
U1 3
U2 8
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1551-7144
J9 CONTEMP CLIN TRIALS
JI Contemp. Clin. Trials
PD MAR
PY 2012
VL 33
IS 2
BP 386
EP 395
DI 10.1016/j.cct.2011.11.001
PG 10
WC Medicine, Research & Experimental; Pharmacology & Pharmacy
SC Research & Experimental Medicine; Pharmacology & Pharmacy
GA 901JA
UT WOS:000300962000018
PM 22085803
ER
PT J
AU Bornstein, MH
Putnick, DL
AF Bornstein, Marc H.
Putnick, Diane L.
TI Stability of Language in Childhood: A Multiage, Multidomain,
Multimeasure, and Multisource Study
SO DEVELOPMENTAL PSYCHOLOGY
LA English
DT Article
DE language development; stability; preschool
ID YOUNG-CHILDREN; FIT INDEXES; COMMUNICATIVE DEVELOPMENT;
INDIVIDUAL-DIFFERENCES; PRESCHOOL-CHILDREN; EARLY VOCABULARY; PRODUCTIVE
VOCABULARY; EXPRESSIVE LANGUAGE; PREDICTIVE-VALIDITY; CONSISTENCY
AB The stability of language across childhood is traditionally assessed by exploring longitudinal relations between individual language measures. However, language encompasses many domains and varies with different sources (child speech, parental report, experimenter assessment). This study evaluated individual variation in multiple age-appropriate measures of child language derived from multiple sources and stability between their latent variables in 192 young children across more than 2 years. Structural equation modeling demonstrated the loading of multiple measures of child language from different sources on single latent variables of language at ages 20 months and 48 months. A large stability coefficient (r = .84) obtained between the 2 language latent variables. This stability obtained even when accounting for family socioeconomic status, maternal verbal intelligence, education, speech, tendency to respond in a socially desirable fashion, and child social competence. Stability was also equivalent for children in diverse childcare situations and for girls and boys. Across age, from the beginning of language acquisition to just before school entry, aggregating multiple age-appropriate methods and measures at each age and multiple reporters, children show a strong stability of individual differences in general language development.
C1 [Bornstein, Marc H.; Putnick, Diane L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA.
RP Bornstein, MH (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Rockledge 1,Suite 8030,6705 Rockledge Dr,MSC 7971, Bethesda, MD 20892 USA.
EM marc_h_bornstein@nih.gov
OI Putnick, Diane/0000-0002-6323-749X
FU Intramural NIH HHS [Z01 HD001119-20]
NR 129
TC 15
Z9 16
U1 5
U2 18
PU AMER PSYCHOLOGICAL ASSOC
PI WASHINGTON
PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA
SN 0012-1649
J9 DEV PSYCHOL
JI Dev. Psychol.
PD MAR
PY 2012
VL 48
IS 2
BP 477
EP 491
DI 10.1037/a0025889
PG 15
WC Psychology, Developmental
SC Psychology
GA 901IU
UT WOS:000300961400018
PM 22004343
ER
PT J
AU Andersen, SD
Keijzers, G
Rampakakis, E
Engels, K
Luhn, P
El-Shemerly, M
Nielsen, FC
Du, YH
May, A
Bohr, VA
Ferrari, S
Zannis-Hadjopoulos, M
Fu, HA
Rasmussen, LJ
AF Andersen, Sofie Dabros
Keijzers, Guido
Rampakakis, Emmanouil
Engels, Kim
Luhn, Patricia
El-Shemerly, Mahmoud
Nielsen, Finn Cilius
Du, Yuhong
May, Alfred
Bohr, Vilhelm A.
Ferrari, Stefano
Zannis-Hadjopoulos, Maria
Fu, Haian
Rasmussen, Lene Juel
TI 14-3-3 checkpoint regulatory proteins interact specifically with DNA
repair protein human exonuclease 1 (hEXO1) via a semi-conserved motif
SO DNA REPAIR
LA English
DT Article
DE hEXO1; 14-3-3; DNA repair; Cell cycle control; DNA damage; Protein
phosphorylation
ID HUMAN MISMATCH REPAIR; DOUBLE-STRAND BREAKS; ASSOCIATES IN-VIVO;
SUBCELLULAR-LOCALIZATION; REPLICATION FORKS; STRUCTURAL BASIS; BINDING
PROTEIN; END RESECTION; RAF-1 KINASE; EXOENZYME-S
AB Human exonuclease 1 (hEXO1) acts directly in diverse DNA processing events, including replication, mismatch repair (MMR), and double strand break repair (DSBR), and it was also recently described to function as damage sensor and apoptosis inducer following DNA damage. In contrast, 14-3-3 proteins are regulatory phosphorserine/threonine binding proteins involved in the control of diverse cellular events, including cell cycle checkpoint and apoptosis signaling. hEXO1 is regulated by post-translation Ser/Thr phosphorylation in a yet not fully clarified manner, but evidently three phosphorylation sites are specifically induced by replication inhibition leading to protein ubiquitination and degradation. We demonstrate direct and robust interaction between hEXO1 and six of the seven 14-3-3 isoforms in vitro, suggestive of a novel protein interaction network between DNA repair and cell cycle control. Binding experiments reveal weak affinity of the more selective isoform 14-3-3 sigma but both 14-3-3 isoforms eta and sigma significantly stimulate hEXO1 activity, indicating that these regulatory proteins exert a common regulation mode on hEXO1. Results demonstrate that binding involves the phosphorable amino acid S746 in hEXO1 and most likely a second unidentified binding motif. 14-3-3 associations do not appear to directly influence hEXO1 in vitro nuclease activity or in vitro DNA replication initiation. Moreover, specific phosphorylation variants, including hEXO1 S746A, are efficiently imported to the nucleus; to associate with PCNA in distinct replication foci and respond to DNA double strand breaks (DSBs), indicating that 14-3-3 binding does not involve regulating the subcellular distribution of hEXO1. Altogether, these results suggest that association may be related to regulation of hEXO1 availability during the DNA damage response to plausibly prevent extensive DNA resection at the damage site, as supported by recent studies. (C) 2011 Elsevier B.V. All rights reserved.
C1 [Rasmussen, Lene Juel] Univ Copenhagen, Ctr Hlth Aging, Dept Cellular & Mol Med, DK-2200 Copenhagen, Denmark.
[Andersen, Sofie Dabros] Roskilde Univ Ctr, Dept Sci Syst & Models, Roskilde, Denmark.
[Rampakakis, Emmanouil; Zannis-Hadjopoulos, Maria] Rosalind & Morris Goodman Canc Ctr, Montreal, PQ, Canada.
[Rampakakis, Emmanouil; Zannis-Hadjopoulos, Maria] Dept Biochem, Montreal, PQ, Canada.
[Engels, Kim; El-Shemerly, Mahmoud; Ferrari, Stefano] Univ Zurich, Inst Mol Canc Res, CH-8006 Zurich, Switzerland.
[Luhn, Patricia; Du, Yuhong; Fu, Haian] Emory Univ, Sch Med, Dept Pharmacol, Atlanta, GA 30322 USA.
[Nielsen, Finn Cilius] Univ Copenhagen Hosp, Dept Clin Biochem, Copenhagen, Denmark.
[May, Alfred; Bohr, Vilhelm A.] NIA, Lab Mol Gerontol, Bethesda, MD 20892 USA.
RP Rasmussen, LJ (reprint author), Univ Copenhagen, Ctr Hlth Aging, Dept Cellular & Mol Med, DK-2200 Copenhagen, Denmark.
EM lenera@sund.ku.dk
RI Ferrari, Stefano/I-7357-2016
OI Ferrari, Stefano/0000-0002-6607-215X
FU EU [LSHC-CT-2005-018754]; NORDEA-fonden; Cancer Research Society, Inc.
(Montreal, Canada); Swiss National Science Foundation [31003A-112080];
Promedica-Stiftung (UBS-AG)
FX LJR was supported by EU grant LSHC-CT-2005-018754 and NORDEA-fonden. MZH
was funded by the Cancer Research Society, Inc. (Montreal, Canada). SF
was supported by the Swiss National Science Foundation grant
31003A-112080 and by a grant from the Promedica-Stiftung (UBS-AG).
NR 57
TC 10
Z9 11
U1 0
U2 4
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1568-7864
J9 DNA REPAIR
JI DNA Repair
PD MAR 1
PY 2012
VL 11
IS 3
BP 267
EP 277
DI 10.1016/j.dnarep.2011.11.007
PG 11
WC Genetics & Heredity; Toxicology
SC Genetics & Heredity; Toxicology
GA 905MN
UT WOS:000301276400005
PM 22222486
ER
PT J
AU Covo, S
Westmoreland, JW
Reddy, AK
Gordenin, DA
Resnick, MA
AF Covo, Shay
Westmoreland, James W.
Reddy, Amit K.
Gordenin, Dmitry A.
Resnick, Michael A.
TI RAD53 is limiting in double-strand break repair and in protection
against toxicity associated with ribonucleotide reductase inhibition
SO DNA REPAIR
LA English
DT Article
DE RAD53; Hydroxyurea; Rnr1; Double strand breaks
ID S-PHASE CHECKPOINT; DNA-DAMAGE CHECKPOINT; SACCHAROMYCES-CEREVISIAE;
REPLICATION FORKS; HOMOLOGOUS RECOMBINATION; DNTP POOLS; YEAST;
RESISTANCE; KINASE; ADAPTATION
AB The yeast Chk2/Chk1 homolog Rad53 is a central component of the DNA damage checkpoint system. While it controls genotoxic stress responses such as cell cycle arrest, replication fork stabilization and increase in dNTP pools, little is known about the consequences of reduced Rad53 levels on the various cellular endpoints or about its roles in dealing with chronic vs. acute genotoxic challenges. Using a tetraploid gene dosage model in which only one copy of the yeast RAD53 is functional (simplex), we found that the simplex strain was not sensitive to acute UV radiation or chronic MMS exposure. However, the simplex strain was sensitized to chronic exposure of the ribonucleotide reductase inhibitor hydroxyurea (HU). Surprisingly, reduced RAD53 gene dosage did not affect sensitivity to HU acute exposure, indicating that immediate checkpoint responses and recovery from HU-induced stress were not compromised. Interestingly, cells of most of the colonies that arise after chronic HU exposure acquired heritable resistance to HU. We also found that short HU exposure before and after treatment of G(2) cells with ionizing radiation (IR) reduced the capability of RAD53 simplex cells to repair DSBs, in agreement with sensitivity of RAD53 simplex strain to high doses of IR. We propose that a modest reduction in Rad53 activity can impact the activation of the ribonucleotide reductase catalytic subunit Rnr1 following stress, reducing the ability to generate nucleotide pools sufficient for DNA repair and replication. At the same time, reduced Rad53 activity may lead to genome instability and to the acquisition of drug resistance before and/or during the chronic exposure to HU. These results have implications for developing drug enhancers as well as for understanding mechanisms of drug resistance in cells compromised for DNA damage checkpoint. Published by Elsevier B.V.
C1 [Covo, Shay; Westmoreland, James W.; Reddy, Amit K.; Gordenin, Dmitry A.; Resnick, Michael A.] NIEHS, Chromosome Stabil Grp, Mol Genet Lab, NIH, Res Triangle Pk, NC 27709 USA.
RP Gordenin, DA (reprint author), NIEHS, Chromosome Stabil Grp, Mol Genet Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA.
EM resnick@niehs.nih.gov
OI Gordenin, Dmitry/0000-0002-8399-1836
FU NIEHS (NIH, DHHS) [1Z01ES065073]
FX We greatly appreciate the critical evaluation of the manuscript by Drs.
Jeffrey Stumpf, Kin Chan, and Anders Clausen. This work was supported by
the Intramural Research Program of the NIEHS (NIH, DHHS) under project
1Z01ES065073 to MAR.
NR 47
TC 3
Z9 3
U1 0
U2 4
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 1568-7864
J9 DNA REPAIR
JI DNA Repair
PD MAR 1
PY 2012
VL 11
IS 3
BP 317
EP 323
DI 10.1016/j.dnarep.2011.12.008
PG 7
WC Genetics & Heredity; Toxicology
SC Genetics & Heredity; Toxicology
GA 905MN
UT WOS:000301276400011
PM 22277748
ER
PT J
AU Tyagi, M
Hashimoto, K
Shoemaker, BA
Wuchty, S
Panchenko, AR
AF Tyagi, Manoj
Hashimoto, Kosuke
Shoemaker, Benjamin A.
Wuchty, Stefan
Panchenko, Anna R.
TI Large-scale mapping of human protein interactome using structural
complexes
SO EMBO REPORTS
LA English
DT Article
DE protein interactions; protein structures; protein complexes; IBIS
ID INTERACTION NETWORKS; GENOME; EVOLUTIONARY; SIMILARITIES; SOFTWARE;
BIOLOGY; SERVER
AB Although the identification of protein interactions by high-throughput (HTP) methods progresses at a fast pace, 'interactome' data sets still suffer from high rates of false positives and low coverage. To map the human protein interactome, we describe a new framework that uses experimental evidence on structural complexes, the atomic details of binding interfaces and evolutionary conservation. The structurally inferred interaction network is highly modular and more functionally coherent compared with experimental interaction networks derived from multiple literature citations. Moreover, structurally inferred and high-confidence HTP networks complement each other well, allowing us to construct a merged network to generate testable hypotheses and provide valuable experimental leads.
C1 [Tyagi, Manoj; Hashimoto, Kosuke; Shoemaker, Benjamin A.; Wuchty, Stefan; Panchenko, Anna R.] NIH, Natl Ctr Biotechnol Informat, US Natl Lib Med, Bethesda, MD 20894 USA.
RP Panchenko, AR (reprint author), NIH, Natl Ctr Biotechnol Informat, US Natl Lib Med, 8600 Rockville Pike, Bethesda, MD 20894 USA.
EM panch@ncbi.nlm.nih.gov
RI Tyagi, Manoj/K-8438-2014
FU National Institutes of Health/Department of Health and Human Service
(National Library of Medicine)
FX This work was supported by National Institutes of Health/Department of
Health and Human Service (Intramural Research program of the National
Library of Medicine).
NR 22
TC 22
Z9 22
U1 0
U2 2
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1469-221X
J9 EMBO REP
JI EMBO Rep.
PD MAR
PY 2012
VL 13
IS 3
BP 266
EP 271
DI 10.1038/embor.2011.261
PG 6
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 902SX
UT WOS:000301061800019
PM 22261719
ER
PT J
AU Hoang, A
Drew, BG
Low, H
Remaley, AT
Nestel, P
Kingwell, BA
Sviridov, D
AF Hoang, Anh
Drew, Brian G.
Low, Hann
Remaley, Alan T.
Nestel, Paul
Kingwell, Bronwyn A.
Sviridov, Dmitri
TI Mechanism of cholesterol efflux in humans after infusion of
reconstituted high-density lipoprotein
SO EUROPEAN HEART JOURNAL
LA English
DT Article
DE Lipids; Lipoproteins; Cholesterol
ID TRANSPORT; MACROPHAGES; CAPACITY; PLASMA; CELLS; SIZE
AB Infusion of reconstituted HDL (rHDL) leads to changes in HDL metabolism as well as to an increased capacity of plasma to support cholesterol efflux providing an opportunity to investigate mechanisms linking cholesterol efflux to changes in plasma HDL.
Patient plasmas after infusion of rHDL were tested ex vivo for their capacity to stimulate cholesterol efflux. Reconstituted HDL enhanced mobilization of cholesterol from tissues in vivo as shown by rising HDL cholesterol concentrations over the infusion period. Infusion of rHDL in vivo led to increased cholesterol efflux ex vivo; surprisingly, removing apoB-containing lipoproteins while preserving all HDL subfractions eliminated this increase. Infusion of rHDL led to the remodelling of plasma HDL; however, the capacity of plasma to support cholesterol efflux did not correlate with changes in the concentrations of any of HDL subfractions. Unmodified rHDL accounted for only a proportion of the increment in cholesterol efflux capacity. Furthermore, studies using HeLa and BHK cells overexpressing ABCA1, ABCG1, and SR-B1 showed that the contribution of these cellular mediators of cholesterol efflux to the enhanced capacity of plasma for the efflux was minimal.
Enhanced cholesterol efflux from tissues requires the presence of apoB-containing lipoproteins and may involve enhanced flow of cholesterol through multiple components of the reverse cholesterol transport pathway rather than being determined by a specific HDL subfraction.
C1 [Hoang, Anh; Drew, Brian G.; Low, Hann; Nestel, Paul; Kingwell, Bronwyn A.; Sviridov, Dmitri] Baker Heart & Diabet Inst, Melbourne, Vic 8008, Australia.
[Remaley, Alan T.] NHLBI, NIH, Bethesda, MD 20892 USA.
RP Sviridov, D (reprint author), Baker Heart & Diabet Inst, POB 6492,St Kilda Rd Cent, Melbourne, Vic 8008, Australia.
EM dmitri.sviridov@bakeridi.edu.au
RI Kingwell, Bronwyn/B-1183-2009; Sviridov, Dmitri/E-7943-2010
FU National Health and Medical Research Council of Australia [526614,
418920]
FX This study was supported by grants #526614 (to D. S.) and #418920 (to B.
K.) from the National Health and Medical Research Council of Australia.
D. S. and B. K. are Fellows of the National Health and Medical Research
Council of Australia. B. G. D. is a Post-Doctoral Training Fellow of the
National Health and Medical Research Council of Australia. rHDL for the
original clinical trial was supplied by CSL Behring.
NR 17
TC 38
Z9 39
U1 0
U2 1
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0195-668X
J9 EUR HEART J
JI Eur. Heart J.
PD MAR
PY 2012
VL 33
IS 5
BP 657
EP 665
DI 10.1093/eurheartj/ehr103
PG 9
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 901YE
UT WOS:000301004400023
PM 21498847
ER
PT J
AU Martinez-Gonzalez, C
Wang, HL
Micklem, BR
Bolam, JP
Mena-Segovia, J
AF Martinez-Gonzalez, Cristina
Wang, Hui-Ling
Micklem, Benjamin R.
Bolam, J. Paul
Mena-Segovia, Juan
TI Subpopulations of cholinergic, GABAergic and glutamatergic neurons in
the pedunculopontine nucleus contain calcium-binding proteins and are
heterogeneously distributed
SO EUROPEAN JOURNAL OF NEUROSCIENCE
LA English
DT Article
DE brainstem; calbindin; calretinin; in situ hybridization; rat; stereology
ID LATERODORSAL TEGMENTAL NUCLEI; NITRIC-OXIDE SYNTHASE; BRAIN-STEM CORE;
PONTOMESENCEPHALIC TEGMENTUM; NONCHOLINERGIC NEURONS; RAT HIPPOCAMPUS;
SQUIRREL-MONKEY; MACAQUE MONKEY; BASAL GANGLIA; PARVALBUMIN
AB Neurons in the pedunculopontine nucleus (PPN) are highly heterogeneous in their discharge properties, their neurochemical markers, their pattern of connectivity and the behavioural processes in which they participate. Three main transmitter phenotypes have been described, cholinergic, GABAergic and glutamatergic, and yet electrophysiological evidence suggests heterogeneity within these subtypes. To gain further insight into the molecular composition of these three populations in the rat, we investigated the pattern of expression of calcium binding proteins (CBPs) across distinct regions of the PPN and in relation to the presence of other neurochemical markers. Calbindin- and calretinin-positive neurons are as abundant as cholinergic neurons, and their expression follows a rostro-caudal gradient, whereas parvalbumin is expressed by a low number of neurons. We observed a high degree of expression of CBPs by GABAergic and glutamatergic neurons, with a large majority of calbindin- and calretinin-positive neurons expressing GAD or VGluT2 mRNA. Notably, CBP-positive neurons expressing GAD mRNA were more concentrated in the rostral PPN, whereas the caudal PPN was characterized by a higher density of CBP-positive neurons expressing VGluT2 mRNA. In contrast to these two large populations, in cholinergic neurons expression of calretinin is observed only in low numbers and expression of calbindin is virtually non-existent. These findings thus identify novel subtypes of cholinergic, GABAergic and glutamatergic neurons based on their expression of CBPs, and further contribute to the notion of the PPN as a highly heterogeneous structure, an attribute that is likely to underlie its functional complexity.
C1 [Martinez-Gonzalez, Cristina; Micklem, Benjamin R.; Bolam, J. Paul; Mena-Segovia, Juan] Univ Oxford, Dept Pharmacol, Med Res Council Anat Neuropharmacol Unit, Oxford OX1 3TH, England.
[Wang, Hui-Ling] NIDA, Intramural Res Program, Biomed Res Ctr, Baltimore, MD USA.
RP Mena-Segovia, J (reprint author), Univ Oxford, Dept Pharmacol, Med Res Council Anat Neuropharmacol Unit, Mansfield Rd, Oxford OX1 3TH, England.
EM juan.mena-segovia@pharm.ox.ac.uk
OI Mena-Segovia, Juan/0000-0002-9991-8254; Bolam, J
Paul/0000-0002-5008-8405
FU Medical Research Council UK; National Institute on Drug Abuse; CONACyT
FX This work was supported by the Medical Research Council UK and by the
Intramural Research Program of the National Institute on Drug Abuse.
C.M.-G. is in receipt of a CONACyT studentship. We thank E. Norman and
K. Whitworth for their technical assistance.
NR 49
TC 21
Z9 21
U1 0
U2 6
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0953-816X
J9 EUR J NEUROSCI
JI Eur. J. Neurosci.
PD MAR
PY 2012
VL 35
IS 5
BP 723
EP 734
DI 10.1111/j.1460-9568.2012.08002.x
PG 12
WC Neurosciences
SC Neurosciences & Neurology
GA 903LW
UT WOS:000301119000009
PM 22356461
ER
PT J
AU Bodelon, C
Madeleine, MM
Johnson, LG
Du, Q
Malkki, M
Petersdorf, EW
Schwartz, SM
AF Bodelon, Clara
Madeleine, Margaret M.
Johnson, Lisa G.
Du, Qin
Malkki, Mari
Petersdorf, Effie W.
Schwartz, Stephen M.
TI Genetic variation in CD83 and risks of cervical and vulvar cancers: A
population-based case-control study
SO GYNECOLOGIC ONCOLOGY
LA English
DT Article
DE Human papillomavirus; Cervix; Vulva; Epidemiology; Genetics
ID SQUAMOUS-CELL CARCINOMA; HUMAN-PAPILLOMAVIRUS; DENDRITIC CELLS;
INTRAEPITHELIAL NEOPLASIA; VARIANTS; ADENOCARCINOMA; METAANALYSIS;
MATURATION; PROGRAM; MARKER
AB Objectives. The CD83 glycoprotein is a marker of dendritic cell maturation that may contribute to the T cell response to oncogenic human papillomavirus (HPV) infection. Whether single nucleotide polymorphisms (SNPs) in CD83 influence the risk of HPV-related genital cancers has not been adequately studied. We investigated whether the common genetic variation of the CD83 region was associated with the risks of cervical and vulvar cancers in a population-based case-control study conducted in the Seattle-Puget Sound Region.
Methods. A total of 17 tagSNPs were genotyped in the CD83 region of 886 cervical cases, 517 vulvar cases and 1100 controls. Odds ratio (OR) and 95% confidence intervals (Cl) were computed to assess the risk of cervical and vulvar cancers. The interaction between the tagSNPs and cigarette smoking was also explored.
Results. TagSNPs in the CD83 chromosomal region were not associated with risk of either cervical or vulvar cancer. TagSNP rs853360 was associated with a decreased risk of cervical squamous cell carcinoma (SCC) (OR=0.80; 95% Cl: 0.66-0.98).
Conclusions. Our results do not suggest that the common genetic variation of CD83 is related to cervical or vulvar cancers. The association between tagSNP rs853360 and risk of cervical SCC is likely to be due to chance. If larger or pooled studies confirm our results, CD83 has little or no influence in the risk of HPV-related cancers. Published by Elsevier Inc.
C1 [Bodelon, Clara; Madeleine, Margaret M.; Johnson, Lisa G.; Schwartz, Stephen M.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA.
[Bodelon, Clara; Madeleine, Margaret M.; Schwartz, Stephen M.] Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA.
[Du, Qin; Malkki, Mari; Petersdorf, Effie W.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA.
RP Bodelon, C (reprint author), NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Room 7003, Rockville, MD 20852 USA.
EM clara.bodelon@nih.gov
OI Schwartz, Stephen/0000-0001-7499-8502
FU National Cancer Institute [R01CA112512, P01CA042792, NO1-CN-67009,
NO1-PC-35142, T32CA009168]; Fred Hutchinson Cancer Research Center
FX This work was supported by the research grants (R01CA112512,
P01CA042792), contracts (NO1-CN-67009, NO1-PC-35142) and a training
grant (T32CA009168 to CB) from the National Cancer Institute, as well as
institutional funding from the Fred Hutchinson Cancer Research Center.
NR 25
TC 5
Z9 5
U1 0
U2 1
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0090-8258
J9 GYNECOL ONCOL
JI Gynecol. Oncol.
PD MAR
PY 2012
VL 124
IS 3
BP 525
EP 528
DI 10.1016/j.ygyno.2011.11.017
PG 4
WC Oncology; Obstetrics & Gynecology
SC Oncology; Obstetrics & Gynecology
GA 898OO
UT WOS:000300751900026
PM 22134374
ER
PT J
AU Glasgow, RE
Kaplan, RM
Ockene, JK
Fisher, EB
Emmons, KM
AF Glasgow, Russell E.
Kaplan, Robert M.
Ockene, Judith K.
Fisher, Edwin B.
Emmons, Karen M.
TI Patient-Reported Measures Of Psychosocial Issues And Health Behavior
Should Be Added To Electronic Health Records
SO HEALTH AFFAIRS
LA English
DT Article
ID CENTERED MEDICAL HOME; PRIMARY-CARE; PHYSICAL-ACTIVITY;
CONTROLLED-TRIAL; FIELD-TEST; DEPRESSION; SATISFACTION; MANAGEMENT
AB Recent legislation and delivery system reform efforts are greatly expanding the use of electronic health records. For these efforts to reach their full potential, they must actively involve patients and include patient-reported information about such topics as health behavior, preferences, and psychosocial functioning. We offer a plan for including standardized, practical patient-reported measures as part of electronic health records, quality and performance indexes, the primary care medical home, and research collaborations. These measures must meet certain criteria, including being valid, reliable, sensitive to change, and available in multiple languages. Clinicians, patients, and policy makers also must be able to understand the measures and take action based on them. Including more patient-reported items in electronic health records would enhance health, patient-centered care, and the capacity to undertake population-based research.
C1 [Glasgow, Russell E.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Kaplan, Robert M.] NIH, Off Behav & Social Sci Res, Bethesda, MD 20892 USA.
[Ockene, Judith K.] Univ Massachusetts, Sch Med, Worcester, MA USA.
[Fisher, Edwin B.] Univ N Carolina, Gillings Sch Global Publ Hlth, Dept Hlth Behav & Hlth Educ, Chapel Hill, NC USA.
[Fisher, Edwin B.] Univ N Carolina, Gillings Sch Global Publ Hlth, Amer Acad Family Phys Fdn, Chapel Hill, NC USA.
[Fisher, Edwin B.] Amer Acad Family Phys Fdn, Peers Progress Program, Leawood, KS USA.
[Emmons, Karen M.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
RP Glasgow, RE (reprint author), NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
EM russ.glasgow@nih.gov
FU Society of Behavioral Medicine Health Policy Committee and Executive
Committee
FX The opinions expressed in this article do not necessarily represent
those of the National Cancer Institute. The authors thank the members of
the Society of Behavioral Medicine Health Policy Committee and Executive
Committee for their support, comments on earlier versions, and work on
the health policy brief that prompted this article.
NR 50
TC 51
Z9 51
U1 8
U2 20
PU PROJECT HOPE
PI BETHESDA
PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA
SN 0278-2715
J9 HEALTH AFFAIR
JI Health Aff.
PD MAR
PY 2012
VL 31
IS 3
BP 497
EP 504
DI 10.1377/hlthaff.2010.1295
PG 8
WC Health Care Sciences & Services; Health Policy & Services
SC Health Care Sciences & Services
GA 904UQ
UT WOS:000301223800006
PM 22392660
ER
PT J
AU Wang, T
Rowland, JG
Parmar, J
Nesterova, M
Seki, T
Rainey, WE
AF Wang, T.
Rowland, J. G.
Parmar, J.
Nesterova, M.
Seki, T.
Rainey, W. E.
TI Comparison of Aldosterone Production Among Human Adrenocortical Cell
Lines
SO HORMONE AND METABOLIC RESEARCH
LA English
DT Article
DE aldosterone; adrenocortical carcinoma; steroidogenesis
ID ACUTE REGULATORY PROTEIN; ANGIOTENSIN-II; STEROIDOGENIC ENZYMES;
SYNTHASE CYTOCHROME-P-450; EXPRESSION PROFILES; GLOMERULOSA CELLS;
ADRENAL ZONATION; GENE-EXPRESSION; CARCINOMA; 11-BETA-HYDROXYLASE
AB Several human adrenocortical cell lines have been used as model systems for aldosterone production. However, these cell lines have not been directly compared with each other. Human adrenal cell lines SW13, CAR47, the NCI-H295 and its sub-strains and sub-clones were compared with regard to aldosterone production and aldosterone synthase (CYP11B2) expression. Culture media was collected 48 h after incubation, aldosterone secretion was measured and the data were normalized to the amount of cell protein. RNA was isolated for microarray analysis and quantitative RT-PCR (qPCR). The cell lines with the highest aldosterone production were further tested with regard to angiotensin II (Ang II) stimulation. Neither aldosterone nor CYP11B2 tran-script were detected in SW13 or CAR47 cells. The aldosterone production by the NCI-H295, H295A, H295R-S1, H295R-S2, H295R-S3, HAC13, HAC15 and HAC50 were 119, 1, 6, 826, 18, 139, 412, and 1 334 (pmol/mg protein/48 h), respectively. H295A and H295R-S1 expressed less CYP11B2 than the commonly used H295R-S3 cells; while NCI-H295, H295R-S2, HAC13, HAC15 and HAC50 expressed 24-, 14-, 3-, 10-, and 35-fold higher CYP11B2 compared with the H295R-S3 cells. When treated with Ang II, NCI-H295, H295RS2, HAC13, HAC15 and HAC50 showed signifi cantly higher aldosterone production than the basal level (p < 0.05). A comparison of the available human adrenal cell lines indicates that the H295R-S2 and the clonal cell lines, HAC13, HAC15 and HAC50 produced the highest levels of aldosterone and responded well to Ang II.
C1 [Wang, T.; Rowland, J. G.; Parmar, J.; Seki, T.; Rainey, W. E.] Georgia Hlth Sci Univ, Dept Physiol, Augusta, GA 30912 USA.
[Wang, T.] Wuhan Univ, Renmin Hosp, Dept Cardiol, Wuhan 430072, Peoples R China.
[Nesterova, M.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Sect Endocrinol Genet, NIH, Ctr Clin, Bethesda, MD USA.
RP Rainey, WE (reprint author), Georgia Hlth Sci Univ, Dept Physiol, 1120 15th St, Augusta, GA 30912 USA.
EM wrainey@georgiahealth.edu
RI WANG, TAO/B-1888-2013
FU National Institutes of Health [DK-43140, DK-069950]; Cardiovascular
Discovery Institute, Georgia Health Sciences University
FX This work was also supported by National Institutes of Health Grants
DK-43140 and DK-069950 (to WER), a Synergy Award from the Cardiovascular
Discovery Institute, Georgia Health Sciences University (to WER).
NR 39
TC 23
Z9 24
U1 0
U2 4
PU GEORG THIEME VERLAG KG
PI STUTTGART
PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY
SN 0018-5043
J9 HORM METAB RES
JI Horm. Metab. Res.
PD MAR
PY 2012
VL 44
IS 3
BP 245
EP 250
DI 10.1055/s-0031-1298019
PG 6
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 905PP
UT WOS:000301285000016
PM 22266826
ER
PT J
AU Fanchiang, SS
Cojocaru, R
Othman, M
Khanna, R
Brooks, MJ
Smith, T
Tang, XL
Maricic, I
Swaroop, A
Kumar, V
AF Fanchiang, Shaohsuan S.
Cojocaru, Radu
Othman, Mohammad
Khanna, Ritu
Brooks, Matthew J.
Smith, Trevor
Tang, Xiaolei
Maricic, Igor
Swaroop, Anand
Kumar, Vipin
TI Global expression profiling of peripheral Qa-1-restricted CD8 alpha
alpha plus TCR alpha beta plus regulatory T cells reveals innate-like
features: Implications for immune-regulatory repertoire
SO HUMAN IMMUNOLOGY
LA English
DT Article
DE CD8(+) Treg; Experimental autoimmune encephalomyelitis; Microarray;
Innate cells; Qa-1; HLA-E
ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; HERPESVIRUS ENTRY MEDIATOR;
MULTIPLE-SCLEROSIS; POSITIVE SELECTION; NEGATIVE REGULATOR; NONCLASSICAL
MHC; SELF-TOLERANCE; ROR-ALPHA; IN-VIVO; RESPONSES
AB Among peripheral regulatory T cells, CD8(+) T cells also play an important role in the maintenance of immune homeostasis. A subset of CD8(+) Treg that express alpha beta T cell receptor (TCR) and CD8 alpha alpha homodimers can recognize TCR-derived peptides in the context of the class Ib MHC molecule Qa-1. To gain a better understanding of the nature and phenotype of CD8 alpha alpha+TCR alpha beta+ Treg, a global gene expression profiling using microarray, real-time quantitative polymerase chain reaction, and flow-cytometric analysis was performed using functional Treg clones and lines. The study findings show that CD8(+) Treg shared gene profile expressed by innate-like lymphocytes, including murine intraepithelial lymphocytes and thymic CD8 alpha alpha+TCR alpha beta+ T-cell populations. In addition, this subset displays differential expression of several key regulatory molecules, including CD200. CD8 alpha alpha(+) Treg expressed higher levels of a number of natural killer cell related receptors and molecules belonging to the TNF superfamily. Collectively, peripheral class Ib-reactive CD8 alpha alpha+TCR alpha beta+ T cells represent a unique regulatory population different from class la major histocompatibility complex restricted conventional T cells. These studies have important implications for the regulatory mechanisms mediated by the CD8(+) Treg population in general. (C) 2012 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.
C1 [Fanchiang, Shaohsuan S.; Smith, Trevor; Tang, Xiaolei; Maricic, Igor; Kumar, Vipin] Torrey Pines Inst Mol Studies, Lab Autoimmun, San Diego, CA 92121 USA.
[Cojocaru, Radu; Brooks, Matthew J.; Swaroop, Anand] NEI, NIH, N NRL, Bethesda, MD 20892 USA.
[Othman, Mohammad; Khanna, Ritu; Brooks, Matthew J.; Swaroop, Anand] Univ Michigan, Dept Ophthalmol & Visual Sci, Ann Arbor, MI 48109 USA.
[Othman, Mohammad; Khanna, Ritu; Brooks, Matthew J.; Swaroop, Anand] Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA.
RP Kumar, V (reprint author), Torrey Pines Inst Mol Studies, Lab Autoimmun, San Diego, CA 92121 USA.
EM vkumar@tpims.org
FU National Institutes of Health [R01AI05227]; MSNRI; DNRG
FX The authors thank Dr Randle Ware for critical reading of the manuscript,
and other members of the Laboratory of Autoimmunity for their kind help.
This work was supported by the National Institutes of Health
(R01AI05227), MSNRI, and DNRG (to V.K.).
NR 60
TC 6
Z9 7
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0198-8859
J9 HUM IMMUNOL
JI Hum. Immunol.
PD MAR
PY 2012
VL 73
IS 3
BP 214
EP 222
DI 10.1016/j.humimm.2011.07.306
PG 9
WC Immunology
SC Immunology
GA 901JY
UT WOS:000300964400002
PM 21889557
ER
PT J
AU Han, S
Koo, HH
Lan, Q
Lee, KM
Park, AK
Park, SK
Sung, H
Ahn, HS
Shin, HY
Kang, HJ
Seo, JJ
Ahn, YO
Kim, H
Rothman, N
Kang, D
AF Han, Sohee
Koo, Hong Hoe
Lan, Qing
Lee, Kyoung-Mu
Park, Ae Kyung
Park, Sue K.
Sung, Hyuna
Ahn, Hyo Seop
Shin, Hee Young
Kang, Hyoung Jin
Seo, Jong Jin
Ahn, Yoon-Ok
Kim, Ho
Rothman, Nathaniel
Kang, Daehee
TI Common variation in genes related to immune response and risk of
childhood leukemia
SO HUMAN IMMUNOLOGY
LA English
DT Article
DE Childhood leukemia; Immune response; Single nucleotide polymorphism
ID ACUTE LYMPHOBLASTIC-LEUKEMIA; POLYMORPHISMS; CANCER; NOTCH;
IDENTIFICATION; CHROMOSOME-11; PROTEIN; CELLS; ACID; 11Q
AB An abnormal immune response to common infection(s) may be a plausible etiological mechanism in childhood leukemia. We investigated whether 931 tagging single nucleotide polymorphisms (SNPs) selected in gene regions related to immune response are associated with childhood leukemia susceptibility in a hospital-based case control study (63 cases and 148 controls) conducted among Korean children. The AT or IT genotype of rs7939734 in Fas-associated protein with death domain (FADD) was associated with increased risk of childhood leukemia compared with the AA genotype (odds ratio [OR] = 2.26, 95% confidence interval [95% CI] = 1.20-4.25, p(trend) = 0.0007, min p = 0.002, false discovery rate [FDR] p = 0.17). The CG or GG genotype of rs2301696 in TRPM5 was associated with decreased risk of childhood leukemia compared with the CC genotype (OR = 0.30, 95% CI = 0.14 0.63, P-trend = 0.002, min p = 0.004, FDR p = 0.17). Our findings suggest that genetic polymorphisms in immune response genes might play a role in childhood leukemia development with limited biologic evidence. (C) 2012 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.
C1 [Han, Sohee; Park, Sue K.; Ahn, Yoon-Ok; Kang, Daehee] Seoul Natl Univ, Coll Med, Dept Prevent Med, Seoul 110799, South Korea.
[Koo, Hong Hoe] Sungkyunkwan Univ, Sch Med, Samsung Med Ctr, Dept Pediat, Seoul 110799, South Korea.
[Lan, Qing; Rothman, Nathaniel] NCI, NIH, Dept Hlth, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Lan, Qing; Rothman, Nathaniel] NCI, NIH, Dept Hlth, Human Serv, Bethesda, MD 20892 USA.
[Lee, Kyoung-Mu] Korea Natl Open Univ, Dept Environm Hlth, Seoul 110799, South Korea.
[Park, Ae Kyung] Sunchon Natl Univ, Coll Pharm, Sunchon 540742, Jeonnam, South Korea.
[Park, Sue K.; Ahn, Hyo Seop; Shin, Hee Young; Kang, Hyoung Jin; Kang, Daehee] Seoul Natl Univ, Canc Res Inst, Seoul 110799, South Korea.
[Sung, Hyuna; Kang, Daehee] Seoul Natl Univ, Grad Sch, Dept Biomed Sci, Seoul 110799, South Korea.
[Ahn, Hyo Seop; Shin, Hee Young; Kang, Hyoung Jin] Seoul Natl Univ, Coll Med, Dept Pediat, Seoul 110799, South Korea.
[Seo, Jong Jin] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Pediat, Seoul 110799, South Korea.
[Kim, Ho] Sch Publ Hlth, Div Epidemiol & Biostat, Seoul 110799, South Korea.
[Kang, Daehee] Seoul Natl Univ, Grad Sch Convergence Sci & Technol, Dept Mol Med & Biopharmaceut Sci, Seoul 110799, South Korea.
[Kang, Daehee] Seoul Natl Univ, Coll Med, Seoul 110799, South Korea.
[Kang, Daehee] Seoul Natl Univ, Coll Pharm, Seoul 110799, South Korea.
RP Kang, D (reprint author), Seoul Natl Univ, Coll Med, Dept Prevent Med, Seoul 110799, South Korea.
EM dhkang@snu.ac.kr
RI Kang, Hyoung Jin/J-2730-2012; Kang, Dae Hee/E-8631-2012; Ahn,
Yoon-Ok/J-5530-2012; Shin, Hee Young/J-2766-2012; Park, Sue
Kyung/J-2757-2012
FU Ministry of Health and Welfare, Republic of Korea [AO030001, 0520290]
FX The authors thank all patients and their parents who consented to
participate in a genetics study related to leukemia. This study was
supported by a grant from the Korea Health 21 R&D Project, Ministry of
Health and Welfare, Republic of Korea (Grant AO030001) and by a grant
from the National R&D Program for Cancer Control, Ministry of Health and
Welfare, Republic of Korea (Grant 0520290).
NR 28
TC 4
Z9 4
U1 0
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0198-8859
J9 HUM IMMUNOL
JI Hum. Immunol.
PD MAR
PY 2012
VL 73
IS 3
BP 316
EP 319
DI 10.1016/j.humimm.2011.12.018
PG 4
WC Immunology
SC Immunology
GA 901JY
UT WOS:000300964400017
PM 22244917
ER
PT J
AU Wildfire, JJ
Gergen, PJ
Sorkness, CA
Mitchell, HE
Calatroni, A
Kattan, M
Szefler, SJ
Teach, SJ
Bloomberg, GR
Wood, RA
Liu, AH
Pongracic, JA
Chmiel, JF
Conroy, K
Rivera-Sanchez, Y
Busse, WW
Morgan, WJ
AF Wildfire, Jeremy J.
Gergen, Peter J.
Sorkness, Christine A.
Mitchell, Herman E.
Calatroni, Agustin
Kattan, Meyer
Szefler, Stanley J.
Teach, Stephen J.
Bloomberg, Gordon R.
Wood, Robert A.
Liu, Andrew H.
Pongracic, Jacqueline A.
Chmiel, James F.
Conroy, Kathleen
Rivera-Sanchez, Yadira
Busse, William W.
Morgan, Wayne J.
TI Development and validation of the Composite Asthma Severity Index-an
outcome measure for use in children and adolescents
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Article
DE Asthma; composite score; morbidity; treatment; exacerbations; symptoms;
severity
ID INNER-CITY CHILDREN; CLINICAL-TRIAL; END-POINTS; EXACERBATIONS;
MANAGEMENT; PROGRAM; PANEL
AB Background: Asthma severity is reflected in many aspects of the disease, including impairment and future risks, particularly for exacerbations. According to the Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma, however, to assess more comprehensively the severity of asthma the level of current treatment needed to maintain a level of control should be included.
Objective: Development and validation of a new instrument, the Composite Asthma Severity Index (CASI), which can quantify disease severity by taking into account impairment, risk, and the amount of medication needed to maintain control. At present, there is no instrument available to measure and assess the multidimensional nature of asthma.
Methods: Twenty-six established asthma investigators, who are part of the National Institutes of Health-supported Inner City Asthma Consortium, participated in a modified Delphi consensus process to identify and weight the dimensions of asthma. Factor analysis was performed to identify independent domains of asthma by using the Asthma Control Evaluation trial. CASI was validated by using the Inner City Anti-IgE Therapy for Asthma trial.
Results: CASI scores include 5 domains: day symptoms and albuterol use, night symptoms and albuterol use, controller treatment, lung function measures, and exacerbations. At Asthma Control Evaluation trial enrollment, CASI ranged from 0 to 17, with a mean of 6.2. CASI was stable, with minimal change in variance after 1 year of treatment. In external validation, CASI detected a 32% larger improvement than did symptoms alone.
Conclusion: CASI retained its discriminatory ability even with low levels of symptoms reported after months of guidelines-directed care. Thus, CASI has the ability to determine the level of asthma severity and provide a composite clinical characterization of asthma. (J Allergy Clin Immunol 2012; 129: 694-701.)
C1 [Wildfire, Jeremy J.; Mitchell, Herman E.; Calatroni, Agustin] Rho Fed Syst Div Inc, Chapel Hill, NC 27517 USA.
[Gergen, Peter J.] NIAID, Bethesda, MD 20892 USA.
[Sorkness, Christine A.; Busse, William W.] Univ Wisconsin, Sch Med & Publ Hlth, Madison, WI USA.
[Kattan, Meyer] Columbia Univ, Coll Phys & Surg, New York, NY USA.
[Szefler, Stanley J.; Liu, Andrew H.] Natl Jewish Hlth, Denver, CO USA.
[Szefler, Stanley J.; Liu, Andrew H.] Univ Colorado, Sch Med, Denver, CO USA.
[Teach, Stephen J.] Childrens Natl Med Ctr, Washington, DC 20010 USA.
[Bloomberg, Gordon R.] Washington Univ, St Louis, MO USA.
[Wood, Robert A.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA.
[Pongracic, Jacqueline A.] Childrens Mem Hosp, Chicago, IL 60614 USA.
[Chmiel, James F.] Rainbow Babies & Childrens Hosp, Cleveland, OH 44106 USA.
[Conroy, Kathleen] Boston Univ, Sch Med, Boston, MA 02118 USA.
[Rivera-Sanchez, Yadira] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA.
[Morgan, Wayne J.] Univ Arizona, Coll Med, Tucson, AZ USA.
RP Wildfire, JJ (reprint author), Rho Fed Syst Div Inc, 6330 Quadrangle Dr, Chapel Hill, NC 27517 USA.
EM jeremy_wildfire@rhoworld.com
FU National Institute of Allergy and Infectious Diseases, National
Institutes of Health [NO1-AI-25496, NO1-JAI-25482]; National Center for
Research Resources, National Institutes of Health [RR00052, M01RR00533,
1UL1RR025771, M01RR00071, 1UL1RR024156, 5UL1RR024992-02,
5M01RR020359-04]; GlaxoSmithKline; National Heart, Lung, and Blood
Institute (NHLBI); National Institute of Environmental Health Sciences
(NIEHS; NIAID; NIH; Environmental Protection Agency; Novartis;
NIAID/NHLBI/NIH
FX This project was funded in whole or in part with federal funds from the
National Institute of Allergy and Infectious Diseases, National
Institutes of Health, under contract nos. NO1-AI-25496 and
NO1-JAI-25482. Additional funds were provided by the National Center for
Research Resources, National Institutes of Health, under grants RR00052,
M01RR00533, 1UL1RR025771, M01RR00071, 1UL1RR024156, 5UL1RR024992-02, and
5M01RR020359-04.; M. Kattan and G. R. Bloomberg have received research
support from the National Institute of Allergy and Infectious Diseases
(NIAID)/National Institutes of Health (NIH). S. J. Szefer has consulted
for GlaxoSmithKline, Genentech, Merck, Boehringer-Ingelheim, Novartis,
and Schering-Plough and has received research support from
GlaxoSmithKline, the National Heart, Lung, and Blood Institute (NHLBI),
the National Institute of Environmental Health Sciences (NIEHS), the
NIAID, the NIH, and the Environmental Protection Agency. R. A. Wood has
consulted for the Asthma and Allergy Foundation of America, received
research support from the NIH, and served on the medical advisory board
for the Food Allergy and Anaphylaxis Network. A. H. Liu has received a
speaker honorarium from Merck. J. A. Pongracic has received research
support from the NIAID. J. F. Chmiel has received research support from
the NIH. W. J. Morgan has consulted for the Cystic Fibrosis Foundation,
Genentech, and Novartis and has received research support from the NIH
and Novartis. W. W. Busse has served on advisory boards for Centocor and
Merck; has consulted for Amgen, AstraZeneca, Novartis, GlaxoSmithKline,
Med-Immune, and Genentech; and has received research support from the
NIAID/NHLBI/NIH. The rest of the authors declare that they have no
relevant conflicts of interest.
NR 22
TC 24
Z9 24
U1 0
U2 3
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD MAR
PY 2012
VL 129
IS 3
BP 694
EP 701
DI 10.1016/j.jaci.2011.12.962
PG 8
WC Allergy; Immunology
SC Allergy; Immunology
GA 904IW
UT WOS:000301189300013
PM 22244599
ER
PT J
AU Kesserwan, C
Sokolic, R
Cowen, EW
Garabedian, E
Heselmeyer-Haddad, K
Lee, CCR
Pittaluga, S
Ortiz, C
Baird, K
Lopez-Terrada, D
Bridge, J
Wayne, AS
Candotti, F
AF Kesserwan, Chimene
Sokolic, Robert
Cowen, Edward W.
Garabedian, Elizabeth
Heselmeyer-Haddad, Kerstin
Lee, Chyi-Chia Richard
Pittaluga, Stefania
Ortiz, Clarymar
Baird, Kristin
Lopez-Terrada, Dolores
Bridge, Julia
Wayne, Alan S.
Candotti, Fabio
TI Multicentric dermatofibrosarcoma protuberans in patients with adenosine
deaminase-deficient severe combined immune deficiency
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Article
DE Severe combined immunodeficiency; adenosine deaminase;
dermatofibrosarcoma; adenosine; fibrosis
ID GIANT-CELL FIBROBLASTOMA; BONE-MARROW TRANSPLANTATION; MICE; CHILDHOOD;
GENETICS; FIBROSIS; CHILDREN; FUSION; TUMORS
AB Background: Dermatofibrosarcoma protuberans (DFSP) is a rare malignant skin tumor associated with a characteristic chromosomal translocation (t[17; 22][q22;q13]) resulting in the COL1A1-platelet-derived growth factor beta (PDGFB) fusion gene. This malignancy is rarely diagnosed in childhood.
Objective: We observed an unexpected high incidence of this DFSP in children affected with adenosine deaminase-deficient severe combined immunodeficiency (ADA-SCID) and set out to evaluate the association of these 2 clinical entities.
Methods: Twelve patients with ADA-SCID were evaluated with a complete dermatologic examination and skin biopsy when indicated. Conventional cytogenetic and molecular analyses (fluorescence in situ hybridization, RT-PCR, or both) were performed when possible.
Results: Eight patients were found to have DFSP. Six patients had multicentric involvement (4-15 lesions), primarily of the trunk and extremities. Most lesions presented as 2- to 15-mm, round atrophic plaques. Nodular lesions were present in 3 patients. In all cases CD34 expression was diffusely positive, and diagnosis was confirmed either by means of cytogenetic analysis, molecular testing, or both. The characteristic DFSP-associated translocation, t(17; 22)(q22; q13), was identified in 6 patients; results of fluorescence in situ hybridization were positive for fusion of the COL1A1 and PDGFB loci in 7 patients; and RTPCR showed the COL1A1-PDGFB fusion transcript in 6 patients.
Conclusions: We describe a previously unrecognized association between ADA-SCID and DFSP with unique features, such as multicentricity and occurrence in early age. We hypothesize that the t(17; 22)(q22; q13) translocation that results in dermal overexpression of PDGFB and favors the development of fibrotic tumors might arise because of the known DNA repair defect in patients with ADA-SCID. Although the natural course of DFSP in the setting of ADA-SCID is unknown, this observation should prompt regular screening for DFSP in patients with ADA-SCID. (J Allergy Clin Immunol 2012; 129: 762-9.)
C1 [Candotti, Fabio] NHGRI, Disorders Immun Sect, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA.
[Kesserwan, Chimene; Sokolic, Robert; Garabedian, Elizabeth; Candotti, Fabio] NHGRI, Med Genet Branch, Bethesda, MD 20892 USA.
[Cowen, Edward W.] NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA.
[Heselmeyer-Haddad, Kerstin; Ortiz, Clarymar] NCI, Sect Canc Genom, NIH, Bethesda, MD 20892 USA.
[Lee, Chyi-Chia Richard; Pittaluga, Stefania] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA.
[Baird, Kristin; Wayne, Alan S.] NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Lopez-Terrada, Dolores] Texas Childrens Hosp, Dept Pathol, Houston, TX 77030 USA.
[Bridge, Julia] Univ Nebraska Med Ctr, Dept Pathol & Microbiol, Omaha, NE USA.
RP Candotti, F (reprint author), NHGRI, Disorders Immun Sect, Genet & Mol Biol Branch, NIH, 49 Convent Dr,Bldg 49,Rm 3A04,MSC 4442, Bethesda, MD 20892 USA.
EM fabio@nhgri.nih.gov
RI Sokolic, Robert/I-6072-2012; Lee, Chyi-Chia/I-1938-2013
OI Lee, Chyi-Chia/0000-0002-5306-7781
FU National Institutes of Health, National Human Genome Research Institute;
National Cancer Institute
FX Supported by the Intramural Research Program of the National Institutes
of Health, National Human Genome Research Institute and National Cancer
Institute.
NR 28
TC 13
Z9 13
U1 0
U2 1
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD MAR
PY 2012
VL 129
IS 3
BP 762
EP U240
DI 10.1016/j.jaci.2011.10.028
PG 9
WC Allergy; Immunology
SC Allergy; Immunology
GA 904IW
UT WOS:000301189300023
PM 22153773
ER
PT J
AU Granada, M
Wilk, JB
Tuzova, M
Strachan, DP
Weidinger, S
Albrecht, E
Gieger, C
Heinrich, J
Himes, BE
Hunninghake, GM
Celedon, JC
Weiss, ST
Cruikshank, WW
Farrer, LA
Center, DM
O'Connor, GT
AF Granada, Mark
Wilk, Jemma B.
Tuzova, Marina
Strachan, David P.
Weidinger, Stephan
Albrecht, Eva
Gieger, Christian
Heinrich, Joachim
Himes, Blanca E.
Hunninghake, Gary M.
Celedon, Juan C.
Weiss, Scott T.
Cruikshank, William W.
Farrer, Lindsay A.
Center, David M.
O'Connor, George T.
TI A genome-wide association study of plasma total IgE concentrations in
the Framingham Heart Study
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Article
DE Total IgE; atopy; asthma; genome-wide association study
ID IMMUNOGLOBULIN-E; ALLERGIC DISEASES; CHILDHOOD ASTHMA; HLA ANTIGENS;
GENE; POPULATION; LINKAGE; STAT6; RISK; SUSCEPTIBILITY
AB Background: Atopy and plasma IgE concentration are genetically complex traits, and the specific genetic risk factors that lead to IgE dysregulation and clinical atopy are an area of active investigation.
Objective: We sought to ascertain the genetic risk factors that lead to IgE dysregulation.
Methods: A genome-wide association study (GWAS) was performed in 6819 participants from the Framingham Heart Study (FHS). Seventy of the top single nucleotide polymorphisms (SNPs) were selected based on P values and linkage disequilibrium among neighboring SNPs and evaluated in a meta-analysis with 5 independent populations from the Cooperative Health Research in the Region of Augsburg cohort, the British 1958 Birth Cohort, and the Childhood Asthma Management Program cohort.
Results: Thirteen SNPs located in the region of 3 genes, FCER1A, signal transducer and activator of transcription 6 (STAT6), and IL13, were found to have genome-wide significance in the FHS cohort GWAS. The most significant SNPs from the 3 regions were rs2251746 (FCER1A, P = 2.11 x 10(-12)), rs1059513 (STAT6, P = 2.87 x 10(-8)), and rs1295686 (IL13, P = 3.55 x 10(-8)). Four additional gene regions, HLA-G, HLA-DQA2, HLA-A, and Duffy blood group, chemokine receptor (DARC), reached genome-wide statistical significance in a meta-analysis combining the FHS and replication cohorts, although the DARC association did not appear independent of SNPs in the nearby FCER1A gene.
Conclusion: This GWAS of the FHS cohort has identified genetic loci in HLA genes that might have a role in the pathogenesis of IgE dysregulation and atopy. It also confirmed the association of the known susceptibility loci FCER1A, STAT6, and IL13 for the dysregulation of total IgE. (J Allergy Clin Immunol 2012;129:840-5.)
C1 [Granada, Mark; Tuzova, Marina; Cruikshank, William W.; Center, David M.; O'Connor, George T.] Boston Univ, Sch Med, Ctr Pulm, Boston, MA 02118 USA.
[Wilk, Jemma B.] Brigham & Womens Hosp, Dept Med, Div Aging, Boston, MA 02115 USA.
[Strachan, David P.] Univ London, Div Community Hlth Sci, London WC1E 7HU, England.
[Weidinger, Stephan] Univ Kiel, Dept Dermatol, D-24098 Kiel, Germany.
[Albrecht, Eva; Gieger, Christian] German Res Ctr Environm Hlth, Inst Genet Epidemiol, Helmholtz Zentrum Munchen, Neuherberg, Germany.
[Heinrich, Joachim] German Res Ctr Environm Hlth, Inst Epidemiol 1, Helmholtz Zentrum Munchen, Neuherberg, Germany.
[Himes, Blanca E.; Hunninghake, Gary M.; Weiss, Scott T.] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA.
[Himes, Blanca E.; Hunninghake, Gary M.; Weiss, Scott T.] Harvard Univ, Sch Med, Dept Med, Boston, MA USA.
[Celedon, Juan C.] Univ Pittsburgh, Div Pediat Pulm Med Allergy & Immunol, Childrens Hosp Pittsburgh, UPMC,Sch Med, Pittsburgh, PA 15260 USA.
[Farrer, Lindsay A.] Boston Univ, Sch Med, Dept Med, Boston, MA 02118 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.
[Farrer, Lindsay A.] Boston Univ, Sch Med, Dept Genet & Genom, 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 02118 USA.
[O'Connor, George T.] NHLBI, Framingham Heart Study, Framingham, MA USA.
RP O'Connor, GT (reprint author), Boston Univ, Sch Med, Ctr Pulm, 72 E Concord St R-304, Boston, MA 02118 USA.
EM goconnor@bu.edu
RI Weidinger, Stephan/C-8461-2011;
OI Farrer, Lindsay/0000-0001-5533-4225; O'Connor,
George/0000-0002-6476-3926; Gieger, Christian/0000-0001-6986-9554
FU Flight Attendant Medical Research Institute; Medical Research Council
[G0000934]; Wellcome Trust [068545/Z/02]; DFG [WE 2678/6-1]; German
Ministry of Education and Research (BMBF) [01GS 0818]; Helmholtz Center
Munich; German National Genome Research Network [01GS0823]; National
Library of Medicine [K08 HL092222, 2T15LM007092-16]; National Institutes
of Health/National Heart, Lung, and Blood Institute [U01 HL075419, U01
HL65899, P01 HL083069, N01 HR16049, T32 HL07427]; [N01 HC 25195]; [P01
AI 050516]
FX G.T.O. and J.B.W. were supported by N01 HC 25195 and P01 AI 050516.
J.B.W. was supported by the Flight Attendant Medical Research Institute.
D. P. S. was supported by Medical Research Council grant G0000934 and
Wellcome Trust grant 068545/Z/02. S. W. was supported by the DFG (grant
WE 2678/6-1) and the German Ministry of Education and Research (BMBF) as
part of the National Genome Research Network (NGFN grant 01GS 0818). C.
G., J.H., and E. A. were supported by Helmholtz Center Munich, German
National Genome Research Network (NGFN-2 and NGFNPlus: 01GS0823) and MC
Health as part of LMUinnovativ. G. M. H. was supported by K08 HL092222.
B. E. H. was supported by 2T15LM007092-16 from the National Library of
Medicine. The Childhood Asthma Management Program Genetics Ancillary
Study is supported by U01 HL075419, U01 HL65899, P01 HL083069, N01
HR16049, and T32 HL07427 from the National Institutes of Health/National
Heart, Lung, and Blood Institute.
NR 38
TC 63
Z9 65
U1 2
U2 8
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD MAR
PY 2012
VL 129
IS 3
BP 840
EP U371
DI 10.1016/j.jaci.2011.09.029
PG 27
WC Allergy; Immunology
SC Allergy; Immunology
GA 904IW
UT WOS:000301189300033
PM 22075330
ER
PT J
AU Venditti, V
Fawzi, NL
Clore, GM
AF Venditti, Vincenzo
Fawzi, Nicolas L.
Clore, G. Marius
TI An efficient protocol for incorporation of an unnatural amino acid in
perdeuterated recombinant proteins using glucose-based media
SO JOURNAL OF BIOMOLECULAR NMR
LA English
DT Article
DE Site-specific labeling; Isotopic labeling; Unnatural amino acids;
Spin-labeling
ID ESCHERICHIA-COLI; PHOSPHOTRANSFERASE SYSTEM; GENETIC INCORPORATION;
ENZYME-I; NMR; DYNAMICS; SPECTROSCOPY; PROBE; CODE
AB The in vivo incorporation of unnatural amino acids into proteins is a well-established technique requiring an orthogonal tRNA/aminoacyl-tRNA synthetase pair specific for the unnatural amino acid that is incorporated at a position encoded by a TAG amber codon. Although this technology provides unique opportunities to engineer protein structures, poor protein yields are usually obtained in deuterated media, hampering its application in the protein NMR field. Here, we describe a novel protocol for incorporating unnatural amino acids into fully deuterated proteins using glucose-based media (which are relevant to the production, for example, of amino acid-specific methyl-labeled proteins used in the study of large molecular weight systems). The method consists of pre-induction of the pEVOL plasmid encoding the tRNA/aminoacyl-tRNA synthetase pair in a rich, H2O-based medium prior to exchanging the culture into a D2O-based medium. Our protocol results in high level of isotopic incorporation (similar to 95%) and retains the high expression level of the target protein observed in Luria-Bertani medium.
C1 [Venditti, Vincenzo; Fawzi, Nicolas L.; Clore, G. Marius] NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
RP Clore, GM (reprint author), NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
EM mariusc@mail.nih.gov
RI Venditti, Vincenzo/A-9411-2013; Fawzi, Nicolas/E-2555-2013; Clore, G.
Marius/A-3511-2008
OI Fawzi, Nicolas/0000-0001-5483-0577; Clore, G. Marius/0000-0003-3809-1027
FU NIH, NIDDK; Office of the Director of the NIH
FX We thank Drs. Mark Fleissner and Wayne Hubbell for generously providing
pAcF and the Scripps Research Institute for the pEVOL plasmid. This work
was supported by funds from the Intramural Program of the NIH, NIDDK,
and the Intramural AIDS Targeted Antiviral Program of the Office of the
Director of the NIH (to G.M.C.).
NR 24
TC 7
Z9 7
U1 2
U2 17
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0925-2738
J9 J BIOMOL NMR
JI J. Biomol. NMR
PD MAR
PY 2012
VL 52
IS 3
BP 191
EP 195
DI 10.1007/s10858-012-9606-9
PG 5
WC Biochemistry & Molecular Biology; Spectroscopy
SC Biochemistry & Molecular Biology; Spectroscopy
GA 905VD
UT WOS:000301303100001
PM 22350951
ER
PT J
AU Shen, Y
Bax, A
AF Shen, Yang
Bax, Ad
TI Identification of helix capping and beta-turn motifs from NMR chemical
shifts
SO JOURNAL OF BIOMOLECULAR NMR
LA English
DT Article
DE Artificial neural network; Backbone chemical shift; Helix capping;
beta-turn; CS-Rosetta; MCC score; Protein structure prediction; Rosetta;
Secondary structure prediction
ID PROTEIN SECONDARY STRUCTURE; NEURAL-NETWORK; STRUCTURE GENERATION;
SEQUENCE HOMOLOGY; ANGLE RESTRAINTS; TORSION ANGLE; WEB SERVER;
AB-INITIO; C-13 NMR; C-ALPHA
AB We present an empirical method for identification of distinct structural motifs in proteins on the basis of experimentally determined backbone and C-13(beta) chemical shifts. Elements identified include the N-terminal and C-terminal helix capping motifs and five types of beta-turns: I, II, I', II' and VIII. Using a database of proteins of known structure, the NMR chemical shifts, together with the PDB-extracted amino acid preference of the helix capping and beta-turn motifs are used as input data for training an artificial neural network algorithm, which outputs the statistical probability of finding each motif at any given position in the protein. The trained neural networks, contained in the MICS (motif identification from chemical shifts) program, also provide a confidence level for each of their predictions, and values ranging from ca 0.7-0.9 for the Matthews correlation coefficient of its predictions far exceed those attainable by sequence analysis. MICS is anticipated to be useful both in the conventional NMR structure determination process and for enhancing on-going efforts to determine protein structures solely on the basis of chemical shift information, where it can aid in identifying protein database fragments suitable for use in building such structures.
C1 [Shen, Yang; Bax, Ad] NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA.
RP Bax, A (reprint author), NIDDKD, Chem Phys Lab, NIH, Bldg 5,Room 126, Bethesda, MD 20892 USA.
EM bax@nih.gov
RI Shen, Yang/C-3064-2008
OI Shen, Yang/0000-0003-1408-8034
FU NIDDK; Office of the Director, NIH
FX We thank Frank Delaglio for helpful comments and suggestions. This work
was funded by the Intramural Research Program of the NIDDK and by the
Intramural AIDS-Targeted Antiviral Program of the Office of the
Director, NIH.
NR 68
TC 38
Z9 38
U1 1
U2 17
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0925-2738
J9 J BIOMOL NMR
JI J. Biomol. NMR
PD MAR
PY 2012
VL 52
IS 3
BP 211
EP 232
DI 10.1007/s10858-012-9602-0
PG 22
WC Biochemistry & Molecular Biology; Spectroscopy
SC Biochemistry & Molecular Biology; Spectroscopy
GA 905VD
UT WOS:000301303100003
PM 22314702
ER
PT J
AU Li, XL
Murray, F
Koide, N
Goldstone, J
Dann, SM
Chen, JZ
Bertin, S
Fu, G
Weinstein, LS
Chen, M
Corr, M
Eckmann, L
Insel, PA
Raz, E
AF Li, Xiangli
Murray, Fiona
Koide, Naoki
Goldstone, Jonathan
Dann, Sara M.
Chen, Jianzhong
Bertin, Samuel
Fu, Guo
Weinstein, Lee S.
Chen, Min
Corr, Maripat
Eckmann, Lars
Insel, Paul A.
Raz, Eyal
TI Divergent requirement for G alpha s and cAMP in the differentiation and
inflammatory profile of distinct mouse Th subsets
SO JOURNAL OF CLINICAL INVESTIGATION
LA English
DT Article
ID GROWTH-FACTOR RECEPTOR; CELL-DIFFERENTIATION; ADENYLATE-CYCLASE;
G-PROTEIN; STIMULATION; CHANNELS; PHOSPHORYLATION; PATHOGENESIS;
ACTIVATION; GENERATION
AB cAMP, the intracellular signaling molecule produced in response to GPCR signaling, has long been recognized as an immunosuppressive agent that inhibits T cell receptor activation and T cell function. However, recent studies show that cAMP also promotes T cell-mediated immunity. Central to cAMP production downstream of GPCR activation is the trimeric G protein Gs. In order to reconcile the reports of divergent effects of cAMP in T cells and to define the direct effect of cAMP in T cells, we engineered mice in which the stimulatory G alpha subunit of Gs (G alpha s) could be deleted in T cells using CD4-Cre (Gnas(Delta CD4)). Gnas(Delta CD4) CD4(+) T cells had reduced cAMP accumulation and Ca2+ influx. In vitro and in vivo, Gnas(Delta cD4) CD4(+) T cells displayed impaired differentiation to specific Th subsets: Th17 and Th1 cells were reduced or absent, but Th2 and regulatory T cells were unaffected. Furthermore, Gnas(Delta CD4) CD4(+) T cells failed to provoke colitis in an adoptive transfer model, indicating reduced inflammatory function. Restoration of cAMP levels rescued the impaired phenotype of Gnas(Delta CD4) CD4(+) T cells, reinstated the PKA-dependent influx of Ca2+, and enhanced the ability of these cells to induce colitis. Our findings thus define an important role for cAMP in the differentiation of Th subsets and their subsequent inflammatory responses, and provide evidence that altering cAMP levels in CD4(+) T cells could provide an immunomodulatory approach targeting specific Th subsets.
C1 [Li, Xiangli; Murray, Fiona; Koide, Naoki; Goldstone, Jonathan; Dann, Sara M.; Chen, Jianzhong; Bertin, Samuel; Corr, Maripat; Eckmann, Lars; Insel, Paul A.; Raz, Eyal] UCSD, Dept Med, La Jolla, CA USA.
[Murray, Fiona; Insel, Paul A.] UCSD, Dept Pharmacol, La Jolla, CA USA.
[Dann, Sara M.] Univ Texas Med Branch, Dept Microbiol, Dept Internal Med, Galveston, TX USA.
[Fu, Guo] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA.
[Weinstein, Lee S.; Chen, Min] NIDDK, Metab Dis Branch, NIH, Bethesda, MD USA.
RP Raz, E (reprint author), Univ Calif San Diego, Dept Med 0663, La Jolla, CA 92093 USA.
EM eraz@ucsd.edu
FU NIH [AI068685, AI095623, AI077989, DK35108, DK080506, T32 AI7469];
Crohn's and Colitis Foundation of America
FX We thank Liang Zhou, Dianel Mucida, Jongdae Lee, and Nakon Aroonsakool
for technical help and discussion. This study was supported by NIH
grants AI068685, AI095623, AI077989, DK35108, DK080506, and T32 AI7469
and a grant from the Crohn's and Colitis Foundation of America.
NR 37
TC 18
Z9 20
U1 2
U2 6
PU AMER SOC CLINICAL INVESTIGATION INC
PI ANN ARBOR
PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA
SN 0021-9738
J9 J CLIN INVEST
JI J. Clin. Invest.
PD MAR
PY 2012
VL 122
IS 3
BP 963
EP 973
DI 10.1172/JCI59097
PG 11
WC Medicine, Research & Experimental
SC Research & Experimental Medicine
GA 902EN
UT WOS:000301021500021
PM 22326954
ER
PT J
AU Brown-Elliott, BA
Biehle, J
Conville, PS
Cohen, S
Saubolle, M
Sussland, D
Wengenack, N
Kriel, K
Bridge, L
McNulty, S
Vasireddy, R
Wallace, RJ
AF Brown-Elliott, Barbara A.
Biehle, Jon
Conville, Patricia S.
Cohen, Samuel
Saubolle, Michael
Sussland, Den
Wengenack, Nancy
Kriel, Kimberly
Bridge, Linda
McNulty, Steven
Vasireddy, Ravikiran
Wallace, Richard J., Jr.
TI Sulfonamide Resistance in Isolates of Nocardia spp. from a US
Multicenter Survey
SO JOURNAL OF CLINICAL MICROBIOLOGY
LA English
DT Article
ID IDENTIFICATION; SUSCEPTIBILITY; EXPERIENCE; FEATURES
AB Recent reports of increasing in vitro sulfonamide resistance in Nocardia prompted us to investigate the findings. Despite the reports, there is a paucity of clinical reports of sulfonamide failure in treatment of nocardia disease. We reviewed 552 recent susceptibilities of clinical isolates of Nocardia from six major laboratories in the United States, and only 2% of the isolates were found to have resistant MICs of trimethoprim-sulfamethoxazole and/or sulfamethoxazole. We hypothesize that the discrepancies in the apparent sulfonamide resistance between our study and the previous findings may be associated with difficulty in the laboratory interpretation of in vitro MICs for trimethoprim-sulfamethoxazole and sulfamethoxazole and the lack of quality controls for Nocardia for these agents.
C1 [Brown-Elliott, Barbara A.; Kriel, Kimberly; Bridge, Linda; McNulty, Steven; Vasireddy, Ravikiran; Wallace, Richard J., Jr.] Univ Texas Hlth Sci Ctr Tyler, Tyler, TX USA.
[Biehle, Jon] Creighton Univ, Med Ctr, Omaha, NE USA.
[Conville, Patricia S.] NIH, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA.
[Cohen, Samuel] Associated & Reg Univ Pathologists, Salt Lake City, UT USA.
[Saubolle, Michael; Sussland, Den] Banner Good Samaritan Med Ctr, Lab Sci Arizona, Phoenix, AZ USA.
[Wengenack, Nancy] Mayo Clin, Rochester, MN USA.
RP Brown-Elliott, BA (reprint author), Univ Texas Hlth Sci Ctr Tyler, Tyler, TX USA.
EM barbara.elliott@uthct.edu
NR 21
TC 26
Z9 28
U1 0
U2 4
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0095-1137
J9 J CLIN MICROBIOL
JI J. Clin. Microbiol.
PD MAR
PY 2012
VL 50
IS 3
BP 670
EP 672
DI 10.1128/JCM.06243-11
PG 3
WC Microbiology
SC Microbiology
GA 901WB
UT WOS:000300997800021
PM 22170936
ER
PT J
AU Sharma-Kuinkel, BK
Ahn, SH
Rude, TH
Zhang, YR
Tong, SYC
Ruffin, F
Genter, FC
Braughton, KR
DeLeo, FR
Barriere, SL
Fowler, VG
AF Sharma-Kuinkel, Batu K.
Ahn, Sun H.
Rude, Thomas H.
Zhang, Yurong
Tong, Steven Y. C.
Ruffin, Felicia
Genter, Fredric C.
Braughton, Kevin R.
DeLeo, Frank R.
Barriere, Steven L.
Fowler, Vance G., Jr.
TI Presence of Genes Encoding Panton-Valentine Leukocidin Is Not the
Primary Determinant of Outcome in Patients with Hospital-Acquired
Pneumonia Due to Staphylococcus aureus
SO JOURNAL OF CLINICAL MICROBIOLOGY
LA English
DT Article
ID METHICILLIN-RESISTANT; VIRULENCE DETERMINANT; NECROTIZING PNEUMONIA;
TREATMENT OPTIONS; ALPHA-HEMOLYSIN; UNITED-STATES; AGR LOCUS; STRAINS;
INFECTIONS; DISEASE
AB The impact of Panton-Valentine leukocidin (PVL) on the outcome in Staphylococcus aureus pneumonia is controversial. We genotyped S. aureus isolates from patients with hospital-acquired pneumonia (HAP) enrolled in two registrational multinational clinical trials for the genetic elements carrying pvl and 30 other virulence genes. A total of 287 isolates (173 methicillin-resistant S. aureus [MRSA] and 114 methicillin-susceptible S. aureus [MSSA] isolates) from patients from 127 centers in 34 countries for whom clinical outcomes of cure or failure were available underwent genotyping. Of these, pvl was detected by PCR and its product confirmed in 23 isolates (8.0%) (MRSA, 18/173 isolates [10.4%]; MSSA, 5/114 isolates [4.4%]). The presence of pvl was not associated with a higher risk for clinical failure (4/23 [17.4%] versus 48/264 [18.2%]; P = 1.00) or mortality. These findings persisted after adjustment for multiple potential confounding variables. No significant associations between clinical outcome and (i) presence of any of the 30 other virulence genes tested, (ii) presence of specific bacterial clone, (iii) levels of alpha-hemolysin, or (iv) delta-hemolysin production were identified. This study suggests that neither pvl presence nor in vitro level of alpha-hemolysin production is the primary determinant of outcome among patients with HAP caused by S. aureus.
C1 [Sharma-Kuinkel, Batu K.; Ahn, Sun H.; Rude, Thomas H.; Zhang, Yurong; Tong, Steven Y. C.; Ruffin, Felicia; Fowler, Vance G., Jr.] Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA.
[Genter, Fredric C.; Barriere, Steven L.] Theravance Inc, San Francisco, CA USA.
[Braughton, Kevin R.; DeLeo, Frank R.] NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, Hamilton, MT USA.
[Fowler, Vance G., Jr.] Duke Clin Res Inst, Durham, NC USA.
[Tong, Steven Y. C.] Menzies Sch Hlth Res, Darwin, NT, Australia.
RP Fowler, VG (reprint author), Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA.
EM fowle003@mc.duke.edu
OI Tong, Steven/0000-0002-1368-8356; DeLeo, Frank/0000-0003-3150-2516
FU Theravance, Inc., South San Francisco, CA; National Institutes of Health
[K24 AI093969]; National Institute of Allergy and Infectious Diseases,
National Institutes of Health; Australian National Health and Medical
Research Council [508829]; Australian-American Fulbright Scholarship;
Royal Australasian College of Physicians Bayer Australia Medical
Research
FX This study was supported by a grant from Theravance, Inc., South San
Francisco, CA. V.G. Fowler was supported in part by K24 AI093969 from
the National Institutes of Health. This research was supported in part
by the Intramural Research Program of the National Institute of Allergy
and Infectious Diseases, National Institutes of Health. S. Y. C. Tong is
supported by an Australian National Health and Medical Research Council
Postdoctoral Training Fellowship (508829), an Australian-American
Fulbright Scholarship, and a Royal Australasian College of Physicians
Bayer Australia Medical Research Fellowship.
NR 49
TC 16
Z9 17
U1 0
U2 3
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0095-1137
J9 J CLIN MICROBIOL
JI J. Clin. Microbiol.
PD MAR
PY 2012
VL 50
IS 3
BP 848
EP 856
DI 10.1128/JCM.06219-11
PG 9
WC Microbiology
SC Microbiology
GA 901WB
UT WOS:000300997800045
PM 22205797
ER
PT J
AU Zeller, M
Patton, JT
Heylen, E
De Coster, S
Ciarlet, M
Van Ranst, M
Matthijnssens, J
AF Zeller, Mark
Patton, John T.
Heylen, Elisabeth
De Coster, Sarah
Ciarlet, Max
Van Ranst, Marc
Matthijnssens, Jelle
TI Genetic Analyses Reveal Differences in the VP7 and VP4 Antigenic
Epitopes between Human Rotaviruses Circulating in Belgium and
Rotaviruses in Rotarix and RotaTeq
SO JOURNAL OF CLINICAL MICROBIOLOGY
LA English
DT Article
ID VACCINE-INTRODUCTION; CHILDHOOD DIARRHEA; GLOBAL SPREAD; UNITED-STATES;
DOUBLE-BLIND; CHILDREN; STRAINS; GASTROENTERITIS; EFFICACY; GENOTYPES
AB Two live-attenuated rotavirus group A (RVA) vaccines, Rotarix (G1P[8]) and RotaTeq (G1-G4, P[8]), have been successfully introduced in many countries worldwide, including Belgium. The parental RVA strains used to generate the vaccines were isolated more than 20 years ago in France (G4 parental strain in RotaTeq) and the United States (all other parental strains). At present, little is known about the relationship between currently circulating human RVAs and the vaccine strains. In this study, we determined sequences for the VP7 and VP4 outer capsid proteins of representative G1P[8], G2P[4], G3P[8], G4P[8], G9P[8], and G12P[8] RVAs circulating in Belgium during 2007 to 2009. The analyses showed that multiple amino acid differences existed between the VP7 and VP4 antigenic epitopes of the vaccine viruses and the Belgian isolates, regardless of their G and P genotypes. However, the highest variability was observed among the circulating G1P[8] RVA strains and the G1 and P[8] components of both RVA vaccines. In particular, RVA strains of the P[8] lineage 4 (OP354-like) showed a significant number of amino acid differences with the P[8] VP4 of both vaccines. In addition, the circulating Belgian G3 RVA strains were found to possibly possess an extra N-linked glycosylation site compared to the G3 RVA vaccine strain of RotaTeq. These results indicate that the antigenic epitopes of RVA strains contained in the vaccines differ substantially from those of the currently circulating RVA strains in Belgium. Over time, these differences might result in selection for strains that escape the RVA neutralizing-antibody pressure induced by vaccines.
C1 [Zeller, Mark; Heylen, Elisabeth; De Coster, Sarah; Van Ranst, Marc; Matthijnssens, Jelle] Univ Louvain, Lab Clin & Epidemiol Virol, Dept Microbiol & Immunol, Rega Inst Med Res, Louvain, Belgium.
[Patton, John T.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
[Ciarlet, Max] Novartis Vaccines & Diagnost Inc, Clin Res & Dev, Cambridge, MA USA.
RP Matthijnssens, J (reprint author), Univ Louvain, Lab Clin & Epidemiol Virol, Dept Microbiol & Immunol, Rega Inst Med Res, Louvain, Belgium.
EM jelle.matthijnssens@uz.kuleuven.be
RI Patton, John/P-1390-2014; Matthijnssens, Jelle/A-6770-2015;
Matthijnssens, Jelle/B-8634-2016;
OI Van Ranst, Marc/0000-0002-1674-4157
FU Institute for the Promotion of Innovation through Science and Technology
in Flanders (IWT Vlaanderen); FWO (Fonds voor Wetenschappelijk
Onderzoek); National Institute of Allergy and Infectious Diseases,
National Institutes of Health
FX M.Z. was supported by the Institute for the Promotion of Innovation
through Science and Technology in Flanders (IWT Vlaanderen). J.M. was
supported by an FWO (Fonds voor Wetenschappelijk Onderzoek) postdoctoral
fellowship. J.T.P. was supported by the Intramural Program of the
National Institute of Allergy and Infectious Diseases, National
Institutes of Health.
NR 67
TC 52
Z9 53
U1 1
U2 5
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0095-1137
J9 J CLIN MICROBIOL
JI J. Clin. Microbiol.
PD MAR
PY 2012
VL 50
IS 3
BP 966
EP 976
DI 10.1128/JCM.05590-11
PG 11
WC Microbiology
SC Microbiology
GA 901WB
UT WOS:000300997800062
PM 22189107
ER
PT J
AU Nakagawa, K
Tanaka, N
Morita, M
Sugioka, A
Miyagawa, S
Gonzalez, FJ
Aoyama, T
AF Nakagawa, Kan
Tanaka, Naoki
Morita, Miwa
Sugioka, Atsushi
Miyagawa, Shin-ichi
Gonzalez, Frank J.
Aoyama, Toshifumi
TI PPAR alpha is down-regulated following liver transplantation in mice
SO JOURNAL OF HEPATOLOGY
LA English
DT Article
DE Oxidative stress; Mitochondrial beta-oxidation; Early graft dysfunction;
Liver transplantation; PPAR alpha
ID PROLIFERATOR-ACTIVATED RECEPTORS; ISCHEMIA-REPERFUSION INJURY; HEPATIC
STEATOSIS; FATTY LIVER; T-CELLS; NONALCOHOLIC STEATOHEPATITIS;
PERMEABILITY TRANSITION; TOLERANCE INDUCTION; GRAFT ACCEPTANCE;
GENE-EXPRESSION
AB Background & Aims: Graft dysfunction is one of the major complications after liver transplantation, but its precise mechanism remains unclear. Since steatotic liver grafts are susceptible to post-transplant dysfunction, and peroxisome proliferator-activated receptor (PPAR) alpha plays an important role in the maintenance of hepatic lipid homeostasis, we examined the role of PPAR alpha in liver transplantation.
Methods: Livers were harvested from Sv/129 wild-type (Ppara(+/+)) mice and PPAR alpha-null (Ppara(-/-)) mice and transplanted orthotopically into syngeneic Ppara(+/+) mice.
Results: Hepatocellular damage was unexpectedly milder in transplanted Ppara(-/-) livers compared with Ppara(+/+) ones. This was likely due to decreased lipid peroxides in the Ppara(-/-) livers, as revealed by the lower levels of fatty acid oxidation (FAO) enzymes, which are major sources of reactive oxygen species. Hepatic PPAR alpha and its target genes, such as FAO enzymes and pyruvate dehydrogenase kinase 4, were strongly down-regulated after transplantation, which was associated with increases in hepatic tumor necrosis factor-alpha expression and nuclear factor-kappa B activity. Inhibiting post-transplant PPAR alpha down-regulation by clofibrate treatment markedly augmented oxidative stress and hepatocellular injury.
Conclusions: Down-regulation of PPAR alpha seemed to be an adaptive response to metabolic alterations following liver transplantation. These results provide novel information to the understanding of the pathogenesis of early post-transplant events. (C) 2011 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
C1 [Nakagawa, Kan; Tanaka, Naoki; Aoyama, Toshifumi] Shinshu Univ, Grad Sch Med, Inst Aging & Adaptat, Dept Metab Regulat, Matsumoto, Nagano 3908621, Japan.
[Nakagawa, Kan; Miyagawa, Shin-ichi] Shinshu Univ, Sch Med, Dept Surg, Matsumoto, Nagano 3908621, Japan.
[Tanaka, Naoki] Shinshu Univ, Sch Med, Dept Gastroenterol, Matsumoto, Nagano 3908621, Japan.
[Morita, Miwa; Sugioka, Atsushi] Fujita Hlth Univ, Sch Med, Dept Surg, Toyoake, Aichi, Japan.
[Gonzalez, Frank J.] NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Tanaka, N (reprint author), Shinshu Univ, Grad Sch Med, Inst Aging & Adaptat, Dept Metab Regulat, Asahi 3-1-1, Matsumoto, Nagano 3908621, Japan.
EM tanakan@mail.nih.gov
RI Ji, Haofeng/G-6206-2012
NR 47
TC 4
Z9 4
U1 1
U2 4
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0168-8278
J9 J HEPATOL
JI J. Hepatol.
PD MAR
PY 2012
VL 56
IS 3
BP 586
EP 594
DI 10.1016/j.jhep.2011.08.021
PG 9
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 904TQ
UT WOS:000301221200014
PM 22037025
ER
PT J
AU DiGiovanna, JJ
Kraemer, KH
AF DiGiovanna, John J.
Kraemer, Kenneth H.
TI Shining a Light on Xeroderma Pigmentosum
SO JOURNAL OF INVESTIGATIVE DERMATOLOGY
LA English
DT Review
ID DNA-REPAIR GENE; NUCLEOTIDE-EXCISION-REPAIR; UV-SENSITIVE SYNDROME;
COCKAYNE-SYNDROME; SKIN-CANCER; COMPLEMENTATION GROUP; GROUP-A; MICE
LACKING; GROUP-C; POLYMERASE-ETA
AB Xeroderma pigmentosum (XP) is a rare, autosomal recessive disorder of DNA repair characterized by sun sensitivity and UV radiation-induced skin and mucous membrane cancers. Initially described in 1874 by Moriz Kaposi in Vienna, nearly 100 years later, James Cleaver in San Francisco reported defective DNA repair in XP cells. This eventually provided the basis for a mechanistic link between sun exposure, DNA damage, somatic mutations, and skin cancer. XP cells were found to have defects in seven of the proteins of the nucleotide excision repair pathway and in DNA polymerase eta. XP cells are hypersensitive to killing by UV radiation, and XP cancers have characteristic "UV signature" mutations. Clinical studies at the National Institutes of Health found a nearly 10,000-fold increase in skin cancer in XP patients under the age of 20 years, demonstrating the substantial importance of DNA repair in cancer prevention in the general population. Approximately 25% of XP patients have progressive neurological degeneration with progressive loss of neurons, probably from DNA damage induced by oxidative metabolism, which kills nondividing cells in the nervous system. Interestingly, patients with another disorder, trichothiodystrophy, have defects in some of the same genes as XP, but they have primary developmental abnormalities without an increase in skin cancer.
C1 [DiGiovanna, John J.; Kraemer, Kenneth H.] NCI, DNA Repair Sect, Dermatol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
RP Kraemer, KH (reprint author), NCI, DNA Repair Sect, Dermatol Branch, Ctr Canc Res, Bldg 37,Room 4002,MSC 4258, Bethesda, MD 20892 USA.
EM kraemerk@nih.gov
FU 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. We thank the
patients for participating in our studies, and the XP patient support
groups for helping people with XP and their families.
NR 95
TC 139
Z9 143
U1 4
U2 61
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0022-202X
J9 J INVEST DERMATOL
JI J. Invest. Dermatol.
PD MAR
PY 2012
VL 132
IS 3
BP 785
EP 796
DI 10.1038/jid.2011.426
PN 2
PG 12
WC Dermatology
SC Dermatology
GA 893RW
UT WOS:000300374100006
PM 22217736
ER
PT J
AU Mascia, F
Denning, M
Kopan, R
Yuspa, SH
AF Mascia, Francesca
Denning, Mitchell
Kopan, Raphael
Yuspa, Stuart H.
TI The Black Box Illuminated: Signals and Signaling
SO JOURNAL OF INVESTIGATIVE DERMATOLOGY
LA English
DT Review
ID PROTEIN-KINASE-C; GROWTH-FACTOR RECEPTOR; NF-KAPPA-B; HUMAN
EPIDERMAL-KERATINOCYTES; SQUAMOUS-CELL CARCINOMAS; CALCIUM-SENSING
RECEPTOR; TRANSGENIC MICE; CHEMOKINE EXPRESSION; MOUSE KERATINOCYTES;
TUMOR PROMOTION
AB Unraveling the signaling pathways that transmit information from the cell surface to the nucleus has been a major accomplishment of modern cell and molecular biology. The benefit to humans is seen in the multitude of new therapeutics based on the illumination of these pathways. Although considerable insight has been gained in understanding homeostatic and pathological signaling in the epidermis and other skin compartments, the translation into therapy has been lacking. This review will outline advances made in understanding fundamental signaling in several of the most prominent pathways that control cutaneous development, cell-fate decisions, and keratinocyte growth and differentiation with the anticipation that this insight will contribute to new treatments for troubling skin diseases.
C1 [Mascia, Francesca; Yuspa, Stuart H.] NCI, Lab Canc Biol & Genet, Bethesda, MD 20892 USA.
[Denning, Mitchell] Loyola Univ Chicago, Dept Pathol, Maywood, IL USA.
[Kopan, Raphael] Washington Univ, Sch Med, St Louis, MO USA.
RP Yuspa, SH (reprint author), NCI, Lab Canc Biol & Genet, Bldg 37,Room 4068,37 Convent Dr, Bethesda, MD 20892 USA.
EM yuspas@mail.nih.gov
NR 100
TC 11
Z9 12
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0022-202X
J9 J INVEST DERMATOL
JI J. Invest. Dermatol.
PD MAR
PY 2012
VL 132
IS 3
BP 811
EP 819
DI 10.1038/jid.2011.406
PN 2
PG 9
WC Dermatology
SC Dermatology
GA 893RW
UT WOS:000300374100008
PM 22170487
ER
PT J
AU Kong, HH
Segre, JA
AF Kong, Heidi H.
Segre, Julia A.
TI Skin Microbiome: Looking Back to Move Forward
SO JOURNAL OF INVESTIGATIVE DERMATOLOGY
LA English
DT Review
ID STAPHYLOCOCCUS-EPIDERMIDIS; BACTERIAL BIOTA; BODY HABITATS; DIVERSITY;
INFECTIONS; DEFENSE; DISEASE; PROJECT; LESIONS; FOOT
AB Trillions of bacteria, fungi, viruses, archaea, and small arthropods colonize the skin surface, collectively comprising the skin microbiome. Generations of researchers have classified these microbes as transient versus resident, beneficial versus pathogenic, and collaborators versus adversaries. Culturing and direct sequencing of microbial inhabitants identified distinct populations present at skin surface sites. Herein, we explore the history of this field, describe findings from the current molecular sequencing era, and consider the future of investigating how microbes and antimicrobial therapy contribute to human health.
C1 [Kong, Heidi H.] NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Segre, Julia A.] NHGRI, NIH, Bethesda, MD 20892 USA.
RP Kong, HH (reprint author), NCI, Ctr Canc Res, NIH, 10 Ctr Dr,MSC 1908, Bethesda, MD 20892 USA.
EM konghe@mail.nih.gov; jsegre@nhgri.nih.gov
OI Kong, Heidi/0000-0003-4424-064X
FU Intramural NIH HHS [ZIA BC010938-03, ZIA HG000180-11]
NR 37
TC 78
Z9 83
U1 4
U2 74
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0022-202X
J9 J INVEST DERMATOL
JI J. Invest. Dermatol.
PD MAR
PY 2012
VL 132
IS 3
BP 933
EP 939
DI 10.1038/jid.2011.417
PN 2
PG 7
WC Dermatology
SC Dermatology
GA 893RW
UT WOS:000300374100022
PM 22189793
ER
PT J
AU Millum, J
AF Millum, Joseph
TI Introduction: Case Studies in the Ethics of Mental Health Research
SO JOURNAL OF NERVOUS AND MENTAL DISEASE
LA English
DT Article
DE Research ethics; international; case studies; mental health
ID PLACEBO-CONTROLLED TRIALS; CLINICAL-TRIALS; RISPERIDONE; COUNTRIES;
DISORDERS; EQUIPOISE
AB This collection presents six case studies on the ethics of mental health research, written by scientific researchers and ethicists from around the world. We publish them here as a resource for teachers of research ethics and as a contribution to several ongoing ethical debates. Each consists of a description of a research study that was proposed or carried out and an in-depth analysis of the ethics of the study.
C1 NIH, Ctr Clin, Dept Bioeth, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Millum, J (reprint author), NIH, Ctr Clin, Dept Bioeth, Fogarty Int Ctr, 10-1C118,10 Ctr Dr, Bethesda, MD 20892 USA.
EM millumj@cc.nih.gov
FU Intramural NIH HHS [Z99 CL999999]
NR 39
TC 0
Z9 0
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0022-3018
J9 J NERV MENT DIS
JI J. Nerv. Ment. Dis.
PD MAR
PY 2012
VL 200
IS 3
BP 230
EP 235
DI 10.1097/NMD.0b013e318247cb5b
PG 6
WC Clinical Neurology; Psychiatry
SC Neurosciences & Neurology; Psychiatry
GA 900PX
UT WOS:000300901600008
PM 22373760
ER
PT J
AU Igarashi, M
Kim, HW
Chang, LS
Ma, KZ
Rapoport, SI
AF Igarashi, Miki
Kim, Hyung-Wook
Chang, Lisa
Ma, Kaizong
Rapoport, Stanley I.
TI Dietary n-6 polyunsaturated fatty acid deprivation increases
docosahexaenoic acid metabolism in rat brain
SO JOURNAL OF NEUROCHEMISTRY
LA English
DT Article
DE arachidonic; brain; docosahexaenoic; kinetics; linoleic acid; turnover
ID ALPHA-LINOLENIC ACID; THIN-LAYER CHROMATOGRAPHY; PHOSPHOLIPASE A(2);
SIGNAL-TRANSDUCTION; PUFA DEPRIVATION; NUTRITIONAL DEPRIVATION;
UNANESTHETIZED RATS; GENE-TRANSCRIPTION; LIVER CONVERSION; MAMMALIAN
BRAIN
AB Dietary n-6 polyunsaturated fatty acid (PUFA) deprivation in rodents reduces brain arachidonic acid (20:4n-6) concentration and 20:4n-6-preferring cytosolic phospholipase A2 (cPLA2-IVA) and cyclooxygenase (COX)-2 expression, while increasing brain docosahexaenoic acid (DHA, 22:6n-3) concentration and DHA-selective calcium-independent phospholipase A2 (iPLA2)-VIA expression. We hypothesized that these changes are accompanied by up-regulated brain DHA metabolic rates. Using a fatty acid model, brain DHA concentrations and kinetics were measured in unanesthetized male rats fed, for 15 weeks post-weaning, an n-6 PUFA adequate (31.4 wt% linoleic acid) or deficient (2.7 wt% linoleic acid) diet, each lacking 20:4n-6 and DHA. [1-14C]DHA was infused intravenously, arterial blood was sampled, and the brain was microwaved at 5 min and analyzed. Rats fed the n-6 PUFA deficient compared with adequate diet had significantly reduced n-6 PUFA concentrations in brain phospholipids but increased eicosapentaenoic acid (EPA, 20:5n-3), docosapentaenoic acid n-3 (DPAn-3, 22:5n-3), and DHA (by 9.4%) concentrations, particularly in ethanolamine glycerophospholipid (EtnGpl). Incorporation rates of unesterified DHA from plasma, which represent DHA metabolic loss from brain, were increased 45% in brain phospholipids, as was DHA turnover. Increased DHA metabolism following dietary n-6 PUFA deprivation may increase brain concentrations of antiinflammatory DHA metabolites, which with a reduced brain n-6 PUFA content, likely promotes neuroprotection and alters neurotransmission.
C1 [Igarashi, Miki; Kim, Hyung-Wook; Chang, Lisa; Ma, Kaizong; Rapoport, Stanley I.] NIA, NIH, Brain Physiol & Metab Sect, Bethesda, MD 20892 USA.
RP Igarashi, M (reprint author), Univ Calif Irvine, 2205 McGaugh Hall, Irvine, CA 92697 USA.
EM miki.i@uci.edu
FU National Institute on Aging
FX This research was supported entirely by the Intramural Research Program
of the National Institute on Aging. The authors thank the NIH Fellows
Editorial Board for editorial assistance. No author has a conflict of
interest with regard to this manuscript.
NR 83
TC 13
Z9 13
U1 0
U2 12
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0022-3042
J9 J NEUROCHEM
JI J. Neurochem.
PD MAR
PY 2012
VL 120
IS 6
BP 985
EP 997
DI 10.1111/j.1471-4159.2011.07597.x
PG 13
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 903JL
UT WOS:000301112500012
PM 22117540
ER
PT J
AU Yu, PP
Santiago, LY
Katagiri, Y
Geller, HM
AF Yu, Panpan
Santiago, Lizzie Y.
Katagiri, Yasuhiro
Geller, Herbert M.
TI Myosin II activity regulates neurite outgrowth and guidance in response
to chondroitin sulfate proteoglycans
SO JOURNAL OF NEUROCHEMISTRY
LA English
DT Article
DE blebbistatin; cerebellar granule neuron; CSPG
ID NEURONAL GROWTH CONES; ACTIN-FILAMENT; REGENERATION; DRIVES; RHO;
RECEPTOR; MICE; FLOW; CUES; PHOSPHATASE
AB Chondroitin sulfate proteoglycans (CSPGs) are major components of the extracellular matrix in the CNS that inhibit axonal regeneration after CNS injury. Signaling pathways in neurons triggered by CSPGs are still largely unknown. In this study, using well-characterized in vitro assays for neurite outgrowth and neurite guidance, we demonstrate a major role for myosin II in the response of neurons to CSPGs. We found that the phosphorylation of myosin II regulatory light chains is increased by CSPGs. Specific inhibition of myosin II activity with blebbistatin allows growing neurites to cross onto CSPG-rich areas and increases the length of neurites of neurons growing on CSPGs. Using specific gene knockdown, we demonstrate selective roles for myosin IIA and IIB in these processes. Time lapse microscopy and immunocytochemistry demonstrated that CSPGs also inhibit cell adhesion and cell spreading. Inhibition of myosin II selectively accelerated neurite initiation without altering cell adhesion and spreading on CSPGs.
C1 [Yu, Panpan; Santiago, Lizzie Y.; Katagiri, Yasuhiro; Geller, Herbert M.] NHLBI, NIH, Dev Neurobiol Sect, Cell Biol & Physiol Ctr, Bethesda, MD 20892 USA.
RP Geller, HM (reprint author), NHLBI, NIH, Dev Neurobiol Sect, Cell Biol & Physiol Ctr, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM geller@helix.nih.gov
RI Yu, Panpan/A-4962-2013;
OI Geller, Herbert/0000-0002-7048-6144
FU Intramural NIH HHS [ZIA HL006021-02]
NR 38
TC 15
Z9 16
U1 0
U2 5
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0022-3042
J9 J NEUROCHEM
JI J. Neurochem.
PD MAR
PY 2012
VL 120
IS 6
BP 1117
EP 1128
DI 10.1111/j.1471-4159.2011.07638.x
PG 12
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 903JL
UT WOS:000301112500023
PM 22191382
ER
PT J
AU Miller, AC
Odenkirchen, J
Duhaime, AC
Hicks, R
AF Miller, A. Cate
Odenkirchen, Joanne
Duhaime, Ann-Christine
Hicks, Ramona
TI Common Data Elements for Research on Traumatic Brain Injury: Pediatric
Considerations
SO JOURNAL OF NEUROTRAUMA
LA English
DT Article
DE assessment tools; bioinformatics; CDE; clinical trials; database;
meta-analysis; pediatrics; rehabilitation; research; TBI
ID PSYCHOLOGICAL HEALTH; OUTCOME MEASURES; WORKING GROUP; RECOMMENDATIONS
AB Traumatic brain injury (TBI) is a significant global health problem, with a notably high incidence in children and adolescents. Despite the prevalence of TBI and the disabilities that often follow, research on which to base effective treatment is limited by several challenges, including but not limited to the complexity and heterogeneity of TBI. Even when rigorous methods are employed, the utility of the research may be limited by difficulties in comparing findings across studies resulting from the use of different measures to assess similar TBI study variables. Standardization of definitions and data elements is an important step toward accelerating the process of data sharing that will ultimately lead to a stronger evidence base for treatment advances. To address this need, recommendations for common data elements (CDEs) for research on TBI were developed through a 2009 national initiative. To ensure that the TBI CDE recommendations are relevant to pediatric populations, the National Institute on Disability and Rehabilitation Research (NIDRR) and the National Institute of Neurological Disorders and Stroke (NINDS) called for a review of the original recommendations. Following the process used for the original initiative, multidisciplinary work groups composed of pediatric TBI experts were formed (Demographics and Clinical Assessment; Biomarkers; Neuroimaging; and Outcomes Assessment). Recommendations for modifications and additions to the original CDEs were developed by the work groups, vetted at a 2010 workshop and further refined in preparation for publication. The pediatric considerations for TBI CDEs are described in a series of articles in this journal. This article describes the efforts leading to this pediatric CDE initiative and the CDE review and development process. It concludes with general recommendations for future iterations of the CDE initiative.
C1 [Miller, A. Cate] US Dept Educ, Natl Inst Disabil & Rehabil Res, Washington, DC 20202 USA.
[Odenkirchen, Joanne; Hicks, Ramona] NINDS, NIH, Bethesda, MD 20892 USA.
[Duhaime, Ann-Christine] Massachusetts Gen Hosp, Boston, MA 02114 USA.
RP Miller, AC (reprint author), US Dept Educ, Natl Inst Disabil & Rehabil Res, 400 Maryland Ave SW, Washington, DC 20202 USA.
EM cate.miller@ed.gov
FU National Institute for Disability and Rehabilitation Research of the
United States Department of Education (NIDRR/DoE); National Institute of
Neurological Disorders and Stroke of the National Institutes of Health
(NINDS/NIH)
FX We gratefully acknowledge the working group members and chairpersons for
their dedication of time and expertise to this initiative. Support for
the workshop came from the National Institute for Disability and
Rehabilitation Research of the United States Department of Education
(NIDRR/DoE) and the National Institute of Neurological Disorders and
Stroke of the National Institutes of Health (NINDS/NIH)
NR 14
TC 6
Z9 6
U1 1
U2 5
PU MARY ANN LIEBERT INC
PI NEW ROCHELLE
PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA
SN 0897-7151
J9 J NEUROTRAUM
JI J. Neurotrauma
PD MAR
PY 2012
VL 29
IS 4
BP 634
EP 638
DI 10.1089/neu.2011.1932
PG 5
WC Critical Care Medicine; Clinical Neurology; Neurosciences
SC General & Internal Medicine; Neurosciences & Neurology
GA 901SQ
UT WOS:000300987500003
PM 22091862
ER
PT J
AU Han, PKJ
Lee, M
Reeve, BB
Mariotto, AB
Wang, ZQ
Hays, RD
Yabroff, KR
Topor, M
Feuer, EJ
AF Han, Paul K. J.
Lee, Minjung
Reeve, Bryce B.
Mariotto, Angela B.
Wang, Zhuoqiao
Hays, Ron D.
Yabroff, K. Robin
Topor, Marie
Feuer, Eric J.
TI Development of a Prognostic Model for Six-Month Mortality in Older
Adults With Declining Health
SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT
LA English
DT Article
DE Prognosis; clinical prediction model; elderly; health-related quality of
life
ID QUALITY-OF-LIFE; NURSING-HOME RESIDENTS; ILL CANCER-PATIENTS; MEDICARE
MANAGED CARE; HOSPITALIZED-PATIENTS; SURVIVAL PREDICTION; UNITED-STATES;
HOSPICE USE; ADVANCED DEMENTIA; PALLIATIVE-CARE
AB Context. Estimation of six-month prognosis is essential in hospice referral decisions, but accurate, evidence-based tools to assist in this task are lacking.
Objectives. To develop a new prognostic model, the Patient-Reported Outcome Mortality Prediction Tool (PROMPT), for six-month mortality in community-dwelling elderly patients.
Methods. We used data from the Medicare Health Outcomes Survey linked to vital status information. Respondents were 65 years old or older, with self-reported declining health over the past year (n = 21,870), identified from four Medicare Health Outcomes Survey cohorts (1998-2000, 1999-2001, 2000-2002, and 2001-2003). A logistic regression model was derived to predict six-month mortality, using sociodemographic characteristics, comorbidities, and health-related quality of life (HRQOL), ascertained by measures of activities of daily living and the Medical Outcomes Study Short Form-36 Health Survey; k-fold cross-validation was used to evaluate model performance, which was compared with existing prognostic tools.
Results. The PROMPT incorporated 11 variables, including four HRQOL domains: general health perceptions, activities of daily living, social functioning, and energy/fatigue. The model demonstrated good discrimination (c-statistic = 0.75) and calibration. Overall diagnostic accuracy was superior to existing tools. At cut points of 10%-70%, estimated six-month mortality risk sensitivity and specificity ranged from 0.8% to 83.4% and 51.1% to 99.9%, respectively, and positive likelihood ratios at all mortality risk cut points >= 40% exceeded 5.0. Corresponding positive and negative predictive values were 23.1%-64.1% and 85.3%-94.5%. Over 50% of patients with estimated six-month mortality risk >= 30% died within 12 months.
Conclusion. The PROMPT, a new prognostic model incorporating HRQOL, demonstrates promising performance and potential value for hospice referral decisions. More work is needed to evaluate the model. J Pain Symptom Manage 2012;43:527-539. (C) 2012 U.S. Cancer Pain Relief Committee. Published by Elsevier Inc. All rights reserved.
C1 [Han, Paul K. J.] Maine Med Ctr, Ctr Outcomes Res & Evaluat, Portland, ME 04105 USA.
[Lee, Minjung; Reeve, Bryce B.; Mariotto, Angela B.; Yabroff, K. Robin; Feuer, Eric J.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Wang, Zhuoqiao; Topor, Marie] Informat Management Serv Inc, Silver Spring, MD USA.
[Hays, Ron D.] Univ Calif Los Angeles, Div Gen Internal Med, Los Angeles, CA USA.
RP Han, PKJ (reprint author), Maine Med Ctr, Ctr Outcomes Res & Evaluat, 39 Forest Ave, Portland, ME 04105 USA.
EM hanp@mmc.org
RI Hays, Ronald/D-5629-2013;
OI Yabroff, K. Robin/0000-0003-0644-5572; Han, Paul/0000-0003-0165-1940
FU National Cancer Institute, National Institutes of Health; National
Institute on Aging [P30AG021684, P30-AG028748]; National Center on
Minority Health and Health Disparities [2P20MD000182]
FX This study was supported by intramural research funds from the National
Cancer Institute, National Institutes of Health. Ron Hays was supported
in part by National Institute on Aging grants (P30AG021684 and
P30-AG028748) and a National Center on Minority Health and Health
Disparities grant (2P20MD000182). The authors declare no conflicts of
interest.
NR 83
TC 18
Z9 18
U1 1
U2 10
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0885-3924
J9 J PAIN SYMPTOM MANAG
JI J. Pain Symptom Manage.
PD MAR
PY 2012
VL 43
IS 3
BP 527
EP 539
DI 10.1016/j.jpainsymman.2011.04.015
PG 13
WC Health Care Sciences & Services; Medicine, General & Internal; Clinical
Neurology
SC Health Care Sciences & Services; General & Internal Medicine;
Neurosciences & Neurology
GA 903NY
UT WOS:000301125200008
PM 22071167
ER
PT J
AU Wiktorowicz, JE
English, RD
Wu, Z
Kurosky, A
AF Wiktorowicz, John E.
English, Robert D.
Wu, Zheng
Kurosky, Alexander
TI Model Studies on iTRAQ Modification of Peptides: Sequence-dependent
Reaction Specificity
SO JOURNAL OF PROTEOME RESEARCH
LA English
DT Article
DE quantitative proteomics; iTRAQ; sequence-specific modification; peptide
O-acylation; mass spectrometry; hydroxyl amino acid reactivity
ID ISOBARIC TAGGING REAGENTS; ESCHERICHIA-COLI-CELLS;
PROTEIN-PHOSPHORYLATION; QUANTITATION; TAGS
AB A multiplexed peptide quantification strategy using the iTRAQ reagent has been described for relative measurements of peptides in digested protein mixtures. To validate the chemical specificity of the iTRAQ reaction, we have performed a detailed study of iTRAQ reactivity with two sets of synthetic peptides. The first set of peptides had sequences of Tyr-Xaa-Ser-Glu-Gly-Leu-Ser-Lys and Tyr-Xaa-Ser-Glu-Tyr-Leu-Ser-Lys where Xaa = Ala, Pro, Trp, Tyr, or Glu and was designed to study the extent of O-acylation by iTRAQ, especially hydroxyl-containing residues in different positions. The second set of peptides included Ala-Ser-Glu-His-Ala-Xaa-Tyr-Gly where Xaa = Ser, Thr, or Tyr and was selected to investigate the effect of histidyl residues separated by one amino acid residue from seryl, tyrosyl, or threonyl residues. Our findings indicated that, in addition to variable levels of O-acylation of nonsequence-specific hydroxyl-containing residues, significant sequence-specific O-acylation of seryl, threonyl, and tyrosyl hydroxyls occurred when separated one residue removed from a histidyl residue, that is, (Tyr/Ser)-Xaa-His or His-Xaa-(Tyr/Ser/Thr). This behavior was verified by a separate spiking experiment of one of the first set of peptides into Escherichia coli protein extracts, followed by retention time targeted LC-MS/MS to demonstrate the occurrence of modifications in a complex mixture. These sequence-dependent O-acylation modifications can be confounding factors to accurate MS quantification. Reversal of peptide O-acylation by the iTRAQ reagent can be accomplished by reaction with hydroxylamine with virtually no cleavage of N-acylation and is a recommended modification of the iTRAQ protocol for many applications.
C1 [Wiktorowicz, John E.; Wu, Zheng; Kurosky, Alexander] Univ Texas Med Branch, Dept Biochem & Mol Biol, Galveston, TX 77555 USA.
[Wiktorowicz, John E.; English, Robert D.; Wu, Zheng; Kurosky, Alexander] Univ Texas Med Branch, NHLBI Prote Ctr Airway Inflammat, Galveston, TX 77555 USA.
RP Kurosky, A (reprint author), Univ Texas Med Branch, Dept Biochem & Mol Biol, Galveston, TX 77555 USA.
EM akurosky@utmb.edu
FU National Heart, Lung, and Blood Institute's Proteomics Initiative
[NO1-HV-00245]; National Institute for Environmental Health Sciences
Center [P30-ES006676]; National Institute of Allergy and Infectious
Diseases [P01-AI062885]
FX This work was supported in part by the National Heart, Lung, and Blood
Institute's Proteomics Initiative NO1-HV-00245 (A.K.), National
Institute for Environmental Health Sciences Center grant P30-ES006676
(C. Elferink), and the National Institute of Allergy and Infectious
Diseases grant P01-AI062885 (A. Brasier). We acknowledge Steven Serabin
for peptide synthesis, Drs. Anthony Haag for his MS consultation, and
Kizhake Soman for his assistance in quantifying the frequency of triplet
sequences in the human genome. The costs of publication of this article
were defrayed in part by the payment of page charges. This article must
therefore be hereby marked "advertisement" in accordance with 18 USC
Section 1734 solely to indicate this fact.
NR 15
TC 5
Z9 5
U1 3
U2 19
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1535-3893
J9 J PROTEOME RES
JI J. Proteome Res.
PD MAR
PY 2012
VL 11
IS 3
BP 1512
EP 1520
DI 10.1021/pr2003165
PG 9
WC Biochemical Research Methods
SC Biochemistry & Molecular Biology
GA 900UH
UT WOS:000300916200007
PM 22335824
ER
PT J
AU Wei, BR
Simpson, RM
Johann, DJ
Dwyer, JE
Prieto, DA
Kumar, M
Ye, X
Luke, B
Shive, HR
Webster, JD
Hoover, SB
Veenstra, TD
Blonder, J
AF Wei, Bih-Rong
Simpson, R. Mark
Johann, Donald J., Jr.
Dwyer, Jennifer E.
Prieto, DaRue A.
Kumar, Mia
Ye, Xiaoying
Luke, Brian
Shive, Heather R.
Webster, Joshua D.
Hoover, Shelley B.
Veenstra, Timothy D.
Blonder, Josip
TI Proteomic Profiling of H-Ras-G12V Induced Hypertrophic Cardiomyopathy in
Transgenic Mice Using Comparative LC-MS Analysis of Thin Fresh-Frozen
Tissue Sections
SO JOURNAL OF PROTEOME RESEARCH
LA English
DT Article
DE H-Ras; hypertrophic cardiomyopathy; fresh frozen tissue; methanol-based
solubilization/digestion; comparative proteomic profiling; pathway
analysis; method development
ID CANCER BIOMARKER DISCOVERY; TANDEM MASS-SPECTROMETRY; BETA-CATENIN;
CARDIAC-HYPERTROPHY; DILATED CARDIOMYOPATHY; THERAPEUTIC TARGET; SAMPLE
PREPARATION; CELL-ADHESION; EXPRESSION; PROTEINS
AB Determination of disease-relevant proteomic profiles from limited tissue specimens, such as pathological biopsies and tissues from small model organisms, remains an analytical challenge and a much needed clinical goal. In this study, a transgenic mouse disease model of cardiac-specific H-Ras-G12V induced hypertrophic cardiomyopathy provided a system to explore the potential of using mass spectrometry (MS)-based proteomics to obtain a disease-relevant molecular profile from amount-limited specimens that are routinely used in pathological diagnosis. Our method employs a two-stage methanol-assisted solubilization to digest lysates prepared from 8-mu m-thick fresh-frozen histological tissue sections of diseased/experimental and normal/control hearts. Coupling this approach with a nanoflow reversed-phase liquid chromatography (LC) and a hybrid linear ion trap/Fourier transform-ion cyclotron resonance MS resulted in the identification of 704 and 752 proteins in hypertrophic and wild-type (control) myocardium, respectively. The disease driving H-Ras protein along with vimentin were unambiguously identified by LC-MS in hypertrophic myocardium and cross-validated by immunohistochemistry and western blotting. The pathway analysis involving proteins identified by MS showed strong association of proteomic data with cardiovascular disease. More importantly, the MS identification and subsequent cross-validation of Wnt3a and beta-catenin, in conjunction with IHC identification of phosphorylated GSK-3 beta and nuclear localization of beta-catenin, provided evidence of Wnt/beta-catenin canonical pathway activation secondary to Ras activation in the course of pathogenic myocardial hypertrophic transformation. Our method yields results indicating that the described proteomic approach permits molecular discovery and assessment of differentially expressed proteins regulating H-Ras induced hypertrophic cardiomyopathy. Selected proteins and pathways can be further investigated using immunohistochemical techniques applied to serial tissue sections of similar or different origin.
C1 [Prieto, DaRue A.; Ye, Xiaoying; Veenstra, Timothy D.; Blonder, Josip] NCI, Lab Prote & Analyt Technol, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21702 USA.
[Wei, Bih-Rong; Simpson, R. Mark; Dwyer, Jennifer E.; Kumar, Mia; Shive, Heather R.; Webster, Joshua D.; Hoover, Shelley B.] NCI, Lab Canc Biol & Genet, Ctr Canc Res, Bethesda, MD 20892 USA.
[Johann, Donald J., Jr.] NCI, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA.
[Luke, Brian] NCI, Adv Biomed Comp Ctr, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21702 USA.
RP Blonder, J (reprint author), NCI, Lab Prote & Analyt Technol, Adv Technol Program, SAIC Frederick Inc, Frederick, MD 21702 USA.
EM blonderj@mail.nih.gov
FU Center for Cancer Research, National Cancer Institute (NCI), Bethesda,
MD; National Cancer Institute, National Institutes of Health
[N01-CO-12400]; National Cancer Institute
FX This research was supported by the Intramural Research Program, Center
for Cancer Research, National Cancer Institute (NCI), Bethesda, MD.
Additional support was provided with federal funds from the National
Cancer Institute, National Institutes of Health, under Contract
N01-CO-12400. H.R.S. was a molecular pathology fellow in the NIH
Comparative Biomedical Scientist Training Program supported by the
National Cancer Institute in partnership with the University of
Maryland. 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 United States Government.
NR 42
TC 5
Z9 6
U1 1
U2 10
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1535-3893
J9 J PROTEOME RES
JI J. Proteome Res.
PD MAR
PY 2012
VL 11
IS 3
BP 1561
EP 1570
DI 10.1021/pr200612y
PG 10
WC Biochemical Research Methods
SC Biochemistry & Molecular Biology
GA 900UH
UT WOS:000300916200011
PM 22214408
ER
PT J
AU Olsavsky, AK
Brotman, MA
Rutenberg, JG
Muhrer, EJ
Deveney, CM
Fromm, SJ
Towbin, K
Pine, DS
Leibenluft, E
AF Olsavsky, Aviva K.
Brotman, Melissa A.
Rutenberg, Julia G.
Muhrer, Eli J.
Deveney, Christen M.
Fromm, Stephen J.
Towbin, Kenneth
Pine, Daniel S.
Leibenluft, Ellen
TI Amygdala Hyperactivation During Face Emotion Processing in Unaffected
Youth at Risk for Bipolar Disorder
SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY
LA English
DT Article
DE bipolar; anxiety; endophenotype; fMRI; faces
ID FACIAL EXPRESSIONS; PSYCHIATRIC-DISORDERS; ANXIETY DISORDER;
RATING-SCALE; CHILDREN; DEPRESSION; CONNECTIVITY; ADOLESCENTS;
COMMUNITY; RELATIVES
AB Objective: Youth at familial risk for bipolar disorder (BD) show deficits in face emotion processing, but the neural correlates of these deficits have not been examined. This preliminary study tests the hypothesis that, relative to healthy comparison (HC) subjects, both BD subjects and youth at risk for BD (i.e., those with a first-degree BD relative) will demonstrate amygdala hyperactivation when viewing fearful and happy faces. The at-risk youth were unaffected, in that they had no history of mood disorder. Method: Amygdala activity was examined in 101 unrelated participants, 8 to 18 years old. Age, gender, and IQ-matched groups included BD (N = 32), unaffected at-risk (N = 13), and HC (N = 56). During functional magnetic resonance imaging, participants attended to emotional and nonemotional aspects of fearful and happy faces. Results: While rating their fear of fearful faces, both BD and unaffected at-risk subjects exhibited amygdala hyperactivity versus HC. There were no between-group differences in amygdala activity in response to happy faces. Post-hoc comparisons revealed that, in at-risk youth, familial risk status (offspring versus sibling), presence of Axis I diagnosis (n = 1 attention-deficit/hyperactivity disorder [ADHD], n = 1 social phobia), and history of medication exposure (n = 1) did not influence imaging findings. Conclusions: We found amygdala hyperactivation in both unaffected at-risk and BD youth while rating their fear of fearful faces. These pilot data suggest that both face emotion labeling deficits and amygdala hyperactivity during face processing should receive further study as potential BD endophenotypes. Longitudinal studies should test whether amygdala hyperactivity to fearful faces predicts conversion to BD in at-risk youth. J. Am. Acad. Child Adolesc. Psychiatry, 2012;51(3): 294-303.
C1 [Olsavsky, Aviva K.] Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90095 USA.
[Olsavsky, Aviva K.; Brotman, Melissa A.; Rutenberg, Julia G.; Muhrer, Eli J.; Deveney, Christen M.; Fromm, Stephen J.; Towbin, Kenneth; Pine, Daniel S.; Leibenluft, Ellen] NIMH, Sect Bipolar Spectrum Disorders, Emot & Dev Branch, NIH,US Dept HHS, Bethesda, MD 20892 USA.
RP Olsavsky, AK (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Box 951720,12-159 CHS, Los Angeles, CA 90095 USA.
EM aolsavsky@mednet.ucla.edu
RI Brotman, Melissa/H-7409-2013
FU National Institute of Mental Health; NIH; Pfizer Inc.; Foundation for
NIH from Pfizer Inc.
FX This study was supported by the Intramural Research Program of the
National Institute of Mental Health. Ms. Olsavsky's research was made
possible through the Clinical Research Training Program, a
public-private partnership supported jointly by the NIH and Pfizer Inc.
(via a grant to the Foundation for NIH from Pfizer Inc.).
NR 36
TC 31
Z9 31
U1 0
U2 15
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0890-8567
J9 J AM ACAD CHILD PSY
JI J. Am. Acad. Child Adolesc. Psychiatr.
PD MAR
PY 2012
VL 51
IS 3
BP 294
EP 303
DI 10.1016/j.jaac.2011.12.008
PG 10
WC Psychology, Developmental; Pediatrics; Psychiatry
SC Psychology; Pediatrics; Psychiatry
GA 902IG
UT WOS:000301031200008
PM 22365465
ER
PT J
AU Duan, Q
van Gelderen, P
Duyn, J
AF Duan, Qi
van Gelderen, Peter
Duyn, Jeff
TI Tailored excitation using nonlinear B0-shims
SO MAGNETIC RESONANCE IN MEDICINE
LA English
DT Article
DE high-field MRI; flip angle; wavelength effects; B1 shimming; transmit
sense
ID REDUCED B-1 INHOMOGENEITY; RF PULSE DESIGN; PARALLEL EXCITATION; 7
TESLA; SELECTIVE EXCITATION; HUMAN BRAIN; COIL; TRANSMIT; NMR
AB In high-field MRI, RF flip angle inhomogeneity due to wavelength effects can lead to spatial variations in contrast and sensitivity. Improved flip angle homogeneity can be achieved through multidimensional excitation, but long RF pulse durations limit practical application. A recent approach to reduce RF pulse duration is based on parallel excitation through multiple RF channels. Here, an alternative approach to shorten multidimensional excitation is proposed that makes use of nonlinear spatial variations in the stationary (B0) magnetic field during a B0-sensitive excitation pulse. As initial demonstration, the method was applied to 2D gradient echo (GE) MRI of human brain at 7 T. Using B0 shims with up to second-order spatial dependence, it is demonstrated that root-mean-squared flip angle variation can be reduced from 20 to 11% with RF pulse lengths that are practical for general GE imaging applications without requiring parallel excitation. The method is expected to improve contrast and sensitivity in GE MRI of human brain at high field. Magn Reson Med, 2012. (c) 2011 Wiley Periodicals, Inc.
C1 [Duan, Qi; van Gelderen, Peter; Duyn, Jeff] Natl Inst Neurol Disorders & Stroke, Adv MRI Sect, Lab Funct & Mol Imaging, NIH, Bethesda, MD USA.
RP Duyn, J (reprint author), 10 Ctr Dr,Room B1D724,Bldg 10, Bethesda, MD 20892 USA.
EM jhd@helix.nih.gov
RI Duan, Qi/J-7916-2016
OI Duan, Qi/0000-0002-2407-6611
FU NIH, NINDS
FX This research was supported by the Intramural Research Program of the
NIH, NINDS.
NR 33
TC 4
Z9 4
U1 0
U2 2
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0740-3194
J9 MAGN RESON MED
JI Magn. Reson. Med.
PD MAR
PY 2012
VL 67
IS 3
BP 601
EP 608
DI 10.1002/mrm.23278
PG 8
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 897UO
UT WOS:000300683900002
PM 22222623
ER
PT J
AU Saito, K
Matsumoto, S
Devasahayam, N
Subramanian, S
Munasinghe, JP
Morris, HD
Lizak, MJ
Ardenkjaer-Larsen, JH
Mitchell, JB
Krishna, MC
AF Saito, Keita
Matsumoto, Shingo
Devasahayam, Nallathamby
Subramanian, Sankaran
Munasinghe, Jeeva P.
Morris, H. Douglas
Lizak, Martin J.
Ardenkjaer-Larsen, Jan Henrik
Mitchell, James B.
Krishna, Murali C.
TI Transient decrease in tumor oxygenation after intravenous administration
of pyruvate
SO MAGNETIC RESONANCE IN MEDICINE
LA English
DT Article
DE electron paramagnetic resonance imaging; hyperpolarized 13C MRI; tumor
hypoxia; radiotherapy
ID CANCER; HYPOXIA; THERAPY; CELLS; MICE
AB MRI using hyperpolarized 13C-labeled pyruvate is a promising tool to biochemically profile tumors and monitor their response to therapy. This technique requires injection of pyruvate into tumor-bearing animals. Pyruvate is an endogenous entity but the influence of exogenously injected bolus doses of pyruvate on tumor microenvironment is not well understood. In this study, the effect of injecting a bolus of pyruvate on tumor oxygen status was investigated. EPR oxygen imaging revealed that the partial pressure of oxygen (pO2) in squamous cell carcinoma implanted in mice decreased significantly 30 min after [1-13C]pyruvate injection, but recovered to preinjection levels after 5 h. Dynamic contrast-enhanced-MRI studies showed that, at the dose of pyruvate used, no changes in tumor perfusion were noticed. Immunohistochemical analysis of hypoxic marker pimonidazole independently verified that the squamous cell carcinoma tumor transiently became more hypoxic by pyruvate injection. Efficacy of radiotherapy was suppressed when X-irradiation was delivered during the period of pyruvate-induced transient hypoxia. These results suggest importance of taking into account the transient decrease in tumor pO2 after pyruvate injection in hyperpolarized 13C MRI, because tumor oxygen status is an important factor in determining outcomes of therapies. Magn Reson Med, 2012. (c) 2011 Wiley Periodicals, Inc.
C1 [Saito, Keita; Matsumoto, Shingo; Devasahayam, Nallathamby; Subramanian, Sankaran; Mitchell, James B.; Krishna, Murali C.] NCI, Radiat Biol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Munasinghe, Jeeva P.; Morris, H. Douglas; Lizak, Martin J.] NINDS, NIH, Bethesda, MD 20892 USA.
[Ardenkjaer-Larsen, Jan Henrik] Grove Ctr GC 18, GE Healthcare, Amersham HP7 9LL, England.
RP Krishna, MC (reprint author), NCI, Radiat Biol Branch, Ctr Canc Res, NIH, Bldg 10,Room B3B69, Bethesda, MD 20892 USA.
EM murali@helix.nih.gov
RI Ardenkjar-Larsen, Jan Henrik/B-5765-2017
OI Ardenkjar-Larsen, Jan Henrik/0000-0001-6167-6926
FU Intramural NIH HHS [ZIA BC010476-08]
NR 21
TC 12
Z9 12
U1 1
U2 10
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0740-3194
J9 MAGN RESON MED
JI Magn. Reson. Med.
PD MAR
PY 2012
VL 67
IS 3
BP 801
EP 807
DI 10.1002/mrm.23065
PG 7
WC Radiology, Nuclear Medicine & Medical Imaging
SC Radiology, Nuclear Medicine & Medical Imaging
GA 897UO
UT WOS:000300683900026
PM 22006570
ER
PT J
AU Rahimi, Z
Ahmadian, Z
Akramipour, R
Vaisi-Raygani, A
Rahimi, Z
Parsian, A
AF Rahimi, Zohreh
Ahmadian, Zainab
Akramipour, Reza
Vaisi-Raygani, Asad
Rahimi, Ziba
Parsian, Abbas
TI Thymidylate synthase and methionine synthase polymorphisms are not
associated with susceptibility to childhood acute lymphoblastic leukemia
in Kurdish population from Western Iran
SO MOLECULAR BIOLOGY REPORTS
LA English
DT Article
DE ALL; Gene polymorphism; MS A2756G; TS 28-bp repeat; Western Iran
ID METHYLENETETRAHYDROFOLATE REDUCTASE MTHFR; FOLATE METABOLIC PATHWAY;
GENETIC POLYMORPHISMS; RISK; LYMPHOMA; HAPLOTYPES; CHILDREN; ADULTS
AB In order to determine the influence of polymorphism in thymidylate synthase (TS 28-bp repeat) and methionine synthase (MS A2756G) genes on the susceptibility to acute lymphoblastic leukemia (ALL), 73 children with ALL and 128 age and sex matched unrelated healthy individuals from the Kermanshah Province of Iran were screened. The genotyping of TS 28-bp repeat and MS A2756G polymorphisms were performed by polymerase chain reaction (PCR) and PCR-RFLP, respectively. The frequency of TS 2R allele in patients and controls were 41.5 and 38%, respectively (Odds ratios (OR) = 1.13, 95% CI 0.73-1.74, P = 0.56). The allelic frequency of G allele of MS was higher (25%) in patients compared with healthy subjects (23%) (OR = 1.09, 95% CI 0.67-1.75, P = 0.71). Considering MS AA and TS 3R3R genotypes as reference indicated that individuals with MS GG + TS 2R2R genotypes have 1.3-fold increase in the risk of ALL (OR = 1.3, 95% CI 0.6-2.7, P = 0.5). Our results showed that neither TS 28-bp repeat nor MS A2756G polymorphisms are risk factors for susceptibility to ALL in Western Iran.
C1 [Rahimi, Zohreh; Vaisi-Raygani, Asad] Med Biol Res Ctr, Dept Biochem, Sch Med, Kermanshah 6714869914, Iran.
[Rahimi, Zohreh; Ahmadian, Zainab; Rahimi, Ziba] Kermanshah Univ Med Sci, Med Biol Res Ctr, Kermanshah, Iran.
[Ahmadian, Zainab] Kermanshah Univ Med Sci, Dept Pharmacol, Sch Pharm, Kermanshah, Iran.
[Akramipour, Reza] Kermanshah Univ Med Sci, Dept Pediat Hematol Oncol, Sch Med, Kermanshah, Iran.
[Parsian, Abbas] NIAAA, Div Neurosci & Behav, NIH, Rockville, MD 20852 USA.
RP Rahimi, Z (reprint author), Med Biol Res Ctr, Dept Biochem, Sch Med, Daneshgah Ave, Kermanshah 6714869914, Iran.
EM zrahimi@kums.ac.ir; 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.
NR 27
TC 8
Z9 11
U1 0
U2 2
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0301-4851
J9 MOL BIOL REP
JI Mol. Biol. Rep.
PD MAR
PY 2012
VL 39
IS 3
BP 2195
EP 2200
DI 10.1007/s11033-011-0968-y
PG 6
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 903HS
UT WOS:000301107800016
PM 21643952
ER
PT J
AU Patri, AK
Simanek, E
AF Patri, Anil K.
Simanek, Eric
TI Biological Applications of Dendrimers
SO MOLECULAR PHARMACEUTICS
LA English
DT Editorial Material
C1 [Patri, Anil K.] SAIC Frederick Inc, Nanotechnol Characterizat Lab, Natl Canc Inst Frederick, Frederick, MD 21702 USA.
[Simanek, Eric] Texas Christian Univ, Dept Chem, Ft Worth, TX 76129 USA.
RP Patri, AK (reprint author), SAIC Frederick Inc, Nanotechnol Characterizat Lab, Natl Canc Inst Frederick, Frederick, MD 21702 USA.
EM patria@mail.nih.gov; e.simanek@tcu.edu
RI Nanotechnology Characterization Lab, NCL/K-8454-2012
NR 0
TC 6
Z9 7
U1 3
U2 19
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1543-8384
J9 MOL PHARMACEUT
JI Mol. Pharm.
PD MAR
PY 2012
VL 9
IS 3
BP 341
EP 341
DI 10.1021/mp300057m
PG 1
WC Medicine, Research & Experimental; Pharmacology & Pharmacy
SC Research & Experimental Medicine; Pharmacology & Pharmacy
GA 902DG
UT WOS:000301018200001
PM 22384975
ER
PT J
AU Nwe, K
Milenic, DE
Ray, GL
Kim, YS
Brechbiel, MW
AF Nwe, Kido
Milenic, Diane E.
Ray, Geoffrey L.
Kim, Young-Seung
Brechbiel, Martin W.
TI Preparation of Cystamine Core Dendrimer and Antibody-Dendrimer
Conjugates for MRI Angiography
SO MOLECULAR PHARMACEUTICS
LA English
DT Article
DE magnetic resonance imaging (MRI); cystamine core dendrimer; F(ab ')(2);
antibody
ID GROWTH-FACTOR RECEPTOR; NEUTRON-CAPTURE THERAPY; SINGLE-CHAIN FV;
MONOCLONAL-ANTIBODY; CONTRAST AGENTS; MAGNETIC-RESONANCE; POLYAMIDOAMINE
DENDRIMER; ENHANCEMENT PATTERNS; GADOLINIUM-DENDRIMER; CETUXIMAB
IMC-C225
AB Herein we report the preparation along with the in vivo and in vitro MRI characterization of two generation four and five cystamine core dendrimers loaded with thirty and fifty-eight derivatized Gd-DOTA (G4SS30, GSSS58) respectively. Likewise the development and characterization of two half-dendrimers conjugated to the F(ab')(2) fragment of the monoclonal antibody (mAb) panitumumab functionalized with a maleimide conjugation functional group site (Ab-(G4S15)(4), Ab-(G5S29)(4)) are also described. The in vitro molar relaxivity of the Ab-(G4S15)(4) conjugate, measured at pH 7.4, 22 degrees C, and 3T showed a moderate increase in relaxivity as compared to Magnevist (6.7 vs 4.0 mM(-1) s(-1)) while the Ab-(G5S29)(4) conjugate was 2-fold higher (9.1 vs 4.0 mM(-1) s(-1)). The data showed that only a high injection dose (0.050 mmol Gd3+/kg) produced a detectable contrast enhanced contrast for the Ab-(G4S15)(4) conjugate while a lower dose (0.035 mmol Gd3+/kg) was sufficient for the Ab-(G5S29)(4) conjugate. The antibody-SMCC conjugate was purified by a Sephadex G-100 column, and the antibody-dendrimer-based agents were purified by spin filtration using a Centricon filter (50,000 MCO). The protein assay coupled with cysteine and Ellman's assay indicated an antibody to dendrimer ratio of 1:4. The in vivo blood clearance half-lives of the four agents measured at the jugular vein were similar to 12-22 min.
C1 [Nwe, Kido; Milenic, Diane E.; Ray, Geoffrey L.; Kim, Young-Seung; Brechbiel, Martin W.] NCI, Radioimmune & Inorgan Chem Sect, Radiat Oncol Branch, Bethesda, MD 20892 USA.
RP Brechbiel, MW (reprint author), NCI, Radioimmune & Inorgan Chem Sect, Radiat Oncol Branch, Bldg 10,Room B3B69,10 Ctr Dr MSC 1088, Bethesda, MD 20892 USA.
EM martinwb@mail.nih.gov
FU National Institutes of Health; National Cancer Institute; Center for
Cancer Research; United States Department of Health and Human Services
FX This research was supported by the Intramural Research Program of the
National Institutes of Health, National Cancer Institute, Center for
Cancer Research and the United States Department of Health and Human
Services. We thank Dr. L. Henry Bryant, Jr., Laboratory of Diagnostic
Radiology Research (LDRR), National Institutes of Health, for his help
with the instrumentation for photon correlation spectroscopy (PCS) and
relaxometry.
NR 45
TC 7
Z9 7
U1 3
U2 44
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1543-8384
J9 MOL PHARMACEUT
JI Mol. Pharm.
PD MAR
PY 2012
VL 9
IS 3
BP 374
EP 381
DI 10.1021/mp2003219
PG 8
WC Medicine, Research & Experimental; Pharmacology & Pharmacy
SC Research & Experimental Medicine; Pharmacology & Pharmacy
GA 902DG
UT WOS:000301018200004
PM 21882823
ER
PT J
AU Dobrovolskaia, MA
Patri, AK
Simak, J
Hall, JB
Semberova, J
Lacerda, SHDP
McNeil, SE
AF Dobrovolskaia, Marina A.
Patri, Anil K.
Simak, Jan
Hall, Jennifer B.
Semberova, Jana
Lacerda, Silvia H. De Paoli
McNeil, Scott E.
TI Nanoparticle Size and Surface Charge Determine Effects of PAMAM
Dendrimers on Human Platelets in Vitro
SO MOLECULAR PHARMACEUTICS
LA English
DT Article
DE PAMAM dendrimers; platelets; aggregation; activation; nanomaterials;
thrombogenicity; coagulation; nanoparticles; thrombocyte; dendrimers;
blood; nanomedicine
ID SUPPORTED LIPID-BILAYERS; COARSE-GRAINED MODEL; POLY(AMIDOAMINE)
DENDRIMERS; THROMBUS FORMATION; LATEX-PARTICLES; PROTEIN CORONA; HOLE
FORMATION; AGGREGATION; CELLS; MICROPARTICLES
AB Blood platelets are essential in maintaining hemostasis. Various materials can activate platelets and cause them to aggregate. Platelet aggregation in vitro is often used as a marker for materials thrombogenic properties, and studying nanomaterial interaction with platelets is an important step toward understanding their hematocompatibility. Here we report evaluation of 12 formulations of PAMAM dendrimers varying in size and surface charge. Using a cell counter based method, light transmission aggregometry and scanning electron microscopy, we show that only large cationic dendrimers, but not anionic, neutral or small cationic dendrimers, induce aggregation of human platelets in plasma in vitro. The aggregation caused by large cationic dendrimers was proportional to the number of surface amines. The observed aggregation was not associated with membrane microparticle release, and was insensitive to a variety of chemical and biological inhibitors known to interfere with various pathways of platelet activation. Taken in context with previously reported studies, our data suggest that large cationic PAMAM dendrimers induce platelet aggregation through disruption of membrane integrity.
C1 [Dobrovolskaia, Marina A.; Patri, Anil K.; Hall, Jennifer B.; McNeil, Scott E.] SAIC Frederick Inc, Nanotechnol Characterizat Lab, Adv Technol Program, Frederick, MD 21702 USA.
[Simak, Jan; Semberova, Jana; Lacerda, Silvia H. De Paoli] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA.
RP Dobrovolskaia, MA (reprint author), Lab SAIC Frederick Inc, Nanotechnol Characterizat, NCI Frederick, 1050 Boyles St,Bldg 469, Frederick, MD 21702 USA.
EM marina@mail.nih.gov
RI Nanotechnology Characterization Lab, NCL/K-8454-2012
FU National Cancer Institute, National Institutes of Health [N01-CO-12400,
HHSN261200800001E]
FX This project has been funded in whole or in part with federal funds from
the National Cancer Institute, National Institutes of Health, under
Contract N01-CO-12400 and HHSN261200800001E. The content of this
publication does not necessarily reflect the views or policies of the
Department of Health and Human Services, nor does mention of trade
names, commercial products, or organizations imply endorsement by the
U.S. Government. The 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.
We thank Nader Ayub, Kent Worthington, Barry Neun, David Parmiter and
Jamie Rodriguez for excellent technical support.
NR 45
TC 74
Z9 74
U1 4
U2 47
PU AMER CHEMICAL SOC
PI WASHINGTON
PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA
SN 1543-8384
J9 MOL PHARMACEUT
JI Mol. Pharm.
PD MAR
PY 2012
VL 9
IS 3
BP 382
EP 393
DI 10.1021/mp200463e
PG 12
WC Medicine, Research & Experimental; Pharmacology & Pharmacy
SC Research & Experimental Medicine; Pharmacology & Pharmacy
GA 902DG
UT WOS:000301018200005
PM 22026635
ER
PT J
AU Kohno, T
Ichikawa, H
Totoki, Y
Yasuda, K
Hiramoto, M
Nammo, T
Sakamoto, H
Tsuta, K
Furuta, K
Shimada, Y
Iwakawa, R
Ogiwara, H
Oike, T
Enari, M
Schetter, AJ
Okayama, H
Haugen, A
Skaug, V
Chiku, S
Yamanaka, I
Arai, Y
Watanabe, SI
Sekine, I
Ogawa, S
Harris, CC
Tsuda, H
Yoshida, T
Yokota, J
Shibata, T
AF Kohno, Takashi
Ichikawa, Hitoshi
Totoki, Yasushi
Yasuda, Kazuki
Hiramoto, Masaki
Nammo, Takao
Sakamoto, Hiromi
Tsuta, Koji
Furuta, Koh
Shimada, Yoko
Iwakawa, Reika
Ogiwara, Hideaki
Oike, Takahiro
Enari, Masato
Schetter, Aaron J.
Okayama, Hirokazu
Haugen, Aage
Skaug, Vidar
Chiku, Suenori
Yamanaka, Itaru
Arai, Yasuhito
Watanabe, Shun-ichi
Sekine, Ikuo
Ogawa, Seishi
Harris, Curtis C.
Tsuda, Hitoshi
Yoshida, Teruhiko
Yokota, Jun
Shibata, Tatsuhiro
TI KIF5B-RET fusions in lung adenocarcinoma
SO NATURE MEDICINE
LA English
DT Article
ID CANCER; RET; IDENTIFICATION; THERAPY
AB We identified in-frame fusion transcripts of KIF5B (the kinesin family 5B gene) and the RET oncogene, which are present in 1-2% of lung adenocarcinomas (LADCs) from people from Japan and the United States, using whole-transcriptome sequencing. The KIF5B-RET fusion leads to aberrant activation of RET kinase and is considered to be a new driver mutation of LADC because it segregates from mutations or fusions in EGFR, KRAS, HER2 and ALK, and a RET tyrosine kinase inhibitor, vandetanib, suppresses the fusion-induced anchorage-independent growth activity of NIH3T3 cells.
C1 [Kohno, Takashi; Shimada, Yoko; Ogiwara, Hideaki] Natl Canc Ctr, Res Inst, Div Genome Biol, Chuo Ku, Tokyo 104, Japan.
[Ichikawa, Hitoshi; Sakamoto, Hiromi; Yoshida, Teruhiko] Natl Canc Ctr, Res Inst, Div Genet, Chuo Ku, Tokyo 104, Japan.
[Totoki, Yasushi; Shibata, Tatsuhiro] Natl Canc Ctr, Res Inst, Div Canc Genom, Chuo Ku, Tokyo 104, Japan.
[Yasuda, Kazuki; Hiramoto, Masaki; Nammo, Takao] Natl Ctr Global Hlth & Med, Dept Metab Disorder, Diabet Res Ctr, Res Inst,Shinjuku Ku, Tokyo, Japan.
[Tsuta, Koji; Furuta, Koh; Tsuda, Hitoshi] Natl Canc Ctr, Div Pathol & Clin Labs, Chuo Ku, Tokyo, Japan.
[Iwakawa, Reika; Oike, Takahiro; Okayama, Hirokazu; Yokota, Jun] Natl Canc Ctr, Res Inst, Div Multistep Carcinogenesis, Chuo Ku, Tokyo 104, Japan.
[Enari, Masato] Natl Canc Ctr, Res Inst, Div Refractory Canc Res, Tokyo 104, Japan.
[Schetter, Aaron J.; Okayama, Hirokazu; Harris, Curtis C.] NCI, Human Carcinogenesis Lab, Ctr Canc Res, US Natl Inst Hlth, Bethesda, MD 20892 USA.
[Haugen, Aage; Skaug, Vidar] Natl Inst Occupat Hlth, Sect Toxicol, Dept Chem & Biol Working Environm, Oslo, Norway.
[Chiku, Suenori] Mizuho Informat & Res Inst, Sci Solut Div, Chiyoda Ku, Tokyo, Japan.
[Yamanaka, Itaru] StaGen, Stat Genet Anal Div, Taito Ku, Tokyo, Japan.
[Watanabe, Shun-ichi] Natl Canc Ctr, Div Thorac Surg, Chuo Ku, Tokyo, Japan.
[Sekine, Ikuo] Natl Canc Ctr, Div Thorac Oncol, Chuo Ku, Tokyo, Japan.
[Ogawa, Seishi] Univ Tokyo, Bunkyo Ku, Canc Genom Project, Tokyo 113, Japan.
RP Kohno, T (reprint author), Natl Canc Ctr, Res Inst, Div Genome Biol, Chuo Ku, Tokyo 104, Japan.
EM tkkohno@ncc.go.jp
RI Enari, Masato/E-5507-2014
OI Enari, Masato/0000-0003-4293-3848
FU National Institute of Biomedical Innovation (NiBio); Ministry of Health,
Labour and Welfare; National Cancer Center; Norwegian Cancer Society;
National Cancer Center, Japan
FX This work was supported in part by the program for promotion of
Fundamental Studies in Health Sciences of the National Institute of
Biomedical Innovation (NiBio), Grants-in-Aid from the Ministry of
Health, Labour and Welfare for the 3rd-term Comprehensive 10-year
Strategy for Cancer Control, the National Cancer Center Research and
Development Fund and the Norwegian Cancer Society. National Cancer
Center Biobank is supported by the National Cancer Center Research and
Development Fund, Japan. We thank T. Urushidate, S. Ohashi, S. Mitani,
K. Yokozawa, S. Wakai, C. Otsubo and H. Isomura of the National Cancer
Center and D. Suzuki and K. Nagase of the National Center for Global
Health and Medicine for technical assistance. We also thank J.D. Minna
and L. Girard of the University of Texas Southwestern Medical Center, K.
Kumamoto of Saitama Medical University and A. Okamoto of Jikei
University for RET fusion screening, N. Morii of the National Institute
of Advanced Industrial Science and Technology (AIST) for thermodynamic
characterization of the KIF5B protein and M. Maekawa of the GSP
laboratory for rapid preparation of the FISH probes.
NR 19
TC 298
Z9 317
U1 5
U2 36
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1078-8956
J9 NAT MED
JI Nat. Med.
PD MAR
PY 2012
VL 18
IS 3
BP 375
EP 377
DI 10.1038/nm.2644
PG 3
WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research &
Experimental
SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental
Medicine
GA 905IF
UT WOS:000301264800036
PM 22327624
ER
PT J
AU Thu, MS
Bryant, LH
Coppola, T
Jordan, EK
Budde, MD
Lewis, BK
Chaudhry, A
Ren, JQ
Varma, NRS
Arbab, AS
Frank, JA
AF Thu, Mya S.
Bryant, L. Henry
Coppola, Tiziana
Jordan, E. Kay
Budde, Matthew D.
Lewis, Bobbi K.
Chaudhry, Aneeka
Ren, Jiaqiang
Varma, Nadimpalli Ravi S.
Arbab, Ali S.
Frank, Joseph A.
TI Self-assembling nanocomplexes by combining ferumoxytol, heparin and
protamine for cell tracking by magnetic resonance imaging
SO NATURE MEDICINE
LA English
DT Article
ID STEM-CELLS; DELIVERY-SYSTEM; LABELED CELLS; IRON; NANOPARTICLES; MRI;
OPTIMIZATION; FERUMOXIDES; EXPRESSION; DRUGS
AB We report on a new straightforward magnetic cell-labeling approach that combines three US Food and Drug Administration (FDA)-approved drugs-ferumoxytol, heparin and protamine-in serum-free medium to form self-assembling nanocomplexes that effectively label cells for in vivo magnetic resonance imaging (MRI). We observed that the ferumoxytol-heparin-protamine (HPF) nanocomplexes were stable in serum-free cell culture medium. HPF nanocomplexes show a threefold increase in T2 relaxivity compared to ferumoxytol. Electron microscopy showed internalized HPF in endosomes, which we confirmed by Prussian blue staining of labeled cells. There was no long-term effect or toxicity on cellular physiology or function of HPF-labeled hematopoietic stem cells, bone marrow stromal cells, neural stem cells or T cells when compared to controls. In vivo MRI detected 1,000 HPF-labeled cells implanted in rat brains. This HPF labeling method should facilitate the monitoring by MRI of infused or implanted cells in clinical trials.
C1 [Thu, Mya S.; Bryant, L. Henry; Coppola, Tiziana; Jordan, E. Kay; Budde, Matthew D.; Lewis, Bobbi K.; Chaudhry, Aneeka; Frank, Joseph A.] NIH, Frank Lab, Bethesda, MD 20892 USA.
[Thu, Mya S.; Bryant, L. Henry; Coppola, Tiziana; Jordan, E. Kay; Budde, Matthew D.; Lewis, Bobbi K.; Chaudhry, Aneeka; Frank, Joseph A.] NIH, Lab Diagnost Radiol Res, Dept Radiol & Imaging Sci, Bethesda, MD 20892 USA.
[Ren, Jiaqiang] NIH, Cell Proc Sect, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA.
[Varma, Nadimpalli Ravi S.; Arbab, Ali S.] Henry Ford Hosp, Dept Radiol, Cellular & Mol Imaging Lab, Detroit, MI 48202 USA.
[Frank, Joseph A.] NIH, Natl Inst Biomed Imaging & Bioengn, Bethesda, MD 20892 USA.
RP Frank, JA (reprint author), NIH, Frank Lab, Bldg 10, Bethesda, MD 20892 USA.
EM jafrank@helix.nih.gov
FU Clinical Center of the US National Institutes of Health (NIH); NIH
[R01CA122031]
FX This work was supported by and performed in part in the intramural
research program at the Clinical Center of the US National Institutes of
Health (NIH). BMSCs were provided from the Center for Bone Marrow
Stromal Cell Transplantation at the NIH. NSCs were provided as part of a
material transfer agreement with K. Aboody (City of Hope Medical
Center). The authors would like to acknowledge the Clinical Image
Processing Section at the NIH. This work was also supported by NIH grant
R01CA122031.
NR 38
TC 81
Z9 83
U1 7
U2 54
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1078-8956
J9 NAT MED
JI Nat. Med.
PD MAR
PY 2012
VL 18
IS 3
BP 463
EP U165
DI 10.1038/nm.2666
PG 6
WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research &
Experimental
SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental
Medicine
GA 905IF
UT WOS:000301264800051
PM 22366951
ER
PT J
AU Almering, J
Tsvilovskyy, V
Mannebach, S
Kriebs, U
Weissgerber, P
Flockerzi, V
Birnbaumer, L
Freichel, M
AF Almering, J.
Tsvilovskyy, V.
Mannebach, S.
Kriebs, U.
Weissgerber, P.
Flockerzi, V.
Birnbaumer, L.
Freichel, M.
TI Regulation of mast cell activation by TRP protein-mediated Ca2+ entry
SO NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
LA English
DT Meeting Abstract
CT 78th Annual Congress of the
German-Society-for-Experimental-and-Clinical-Pharmacology-and-Toxicology
(DGPT)
CY MAR 19-22, 2012
CL Dresden, GERMANY
SP German Soc Expt & Clin Pharmacol & Toxicol (DGPT)
C1 [Almering, J.; Tsvilovskyy, V.; Kriebs, U.; Freichel, M.] Univ Heidelberg, Inst Pharmakol, D-69120 Heidelberg, Germany.
[Mannebach, S.; Weissgerber, P.; Flockerzi, V.] Univ Saarlandes Expt & Klin Pharmakol & Toxikol, D-66421 Homburg, Germany.
[Birnbaumer, L.] NIEHS Transmembrane Signaling, Res Triangle Pk, NC 27709 USA.
NR 1
TC 0
Z9 0
U1 1
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0028-1298
J9 N-S ARCH PHARMACOL
JI Naunyn-Schmiedebergs Arch. Pharmacol.
PD MAR
PY 2012
VL 385
SU 1
MA 009
BP 4
EP 4
PG 1
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 898YY
UT WOS:000300779500010
ER
PT J
AU Devanathan, V
Hagedorn, I
Kohler, D
Pexa, K
Piekorz, R
Kraft, P
Stoll, G
Birnbaumer, L
Rosenberger, P
Nieswandt, B
Nurnberg, B
AF Devanathan, V
Hagedorn, I
Koehler, D.
Pexa, K.
Piekorz, R.
Kraft, P.
Stoll, G.
Birnbaumer, L.
Rosenberger, P.
Nieswandt, B.
Nuernberg, B.
TI Different roles for G alpha(i2) and G alpha(i3) in myocardial and
cerebral ischemia
SO NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
LA English
DT Meeting Abstract
CT 78th Annual Congress of the
German-Society-for-Experimental-and-Clinical-Pharmacology-and-Toxicology
(DGPT)
CY MAR 19-22, 2012
CL Dresden, GERMANY
SP German Soc Expt & Clin Pharmacol & Toxicol (DGPT)
C1 [Devanathan, V; Nuernberg, B.] Univ Tubingen, Inst Pharmakol, D-72074 Tubingen, Germany.
[Hagedorn, I; Nieswandt, B.] Univ Wurzburg, Rudolf Virchow Zentrum Expt Biomed, D-97080 Wurzburg, Germany.
[Koehler, D.] Univ Tubingen, Zentrum Hypoxie & Inflammat, D-72074 Tubingen, Germany.
[Pexa, K.; Piekorz, R.] Univ Dusseldorf, Inst Biochem & Mol Biol 2, D-40225 Dusseldorf, Germany.
[Kraft, P.; Stoll, G.] Univ Wurzburg, Neurol Klin & Poliklin, D-97080 Wurzburg, Germany.
[Birnbaumer, L.] NIH, Transmembrane Signaling Grp, Res Triangle Pk, NC 27709 USA.
[Rosenberger, P.] Goethe Univ Frankfurt, Anasthesiol Klin, D-60590 Frankfurt, Germany.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0028-1298
J9 N-S ARCH PHARMACOL
JI Naunyn-Schmiedebergs Arch. Pharmacol.
PD MAR
PY 2012
VL 385
SU 1
MA 085
BP 21
EP 21
PG 1
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 898YY
UT WOS:000300779500086
ER
PT J
AU Mathar, I
Vennekens, R
Mannebach, S
Londono, JEC
Uhl, S
Birnbaumer, L
Voets, T
Freichel, M
AF Mathar, I
Vennekens, R.
Mannebach, S.
Londono, Camacho J. E.
Uhl, S.
Birnbaumer, L.
Voets, T.
Freichel, M.
TI Transient receptor potential channels as mediators of catecholamine
release
SO NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
LA English
DT Meeting Abstract
CT 78th Annual Congress of the
German-Society-for-Experimental-and-Clinical-Pharmacology-and-Toxicology
(DGPT)
CY MAR 19-22, 2012
CL Dresden, GERMANY
SP German Soc Expt & Clin Pharmacol & Toxicol (DGPT)
C1 [Mathar, I; Londono, Camacho J. E.; Uhl, S.; Freichel, M.] Univ Heidelberg, Inst Pharmakol, D-69120 Heidelberg, Germany.
[Vennekens, R.; Voets, T.] KU Leuven Lab Ion Channel Res, B-3000 Louvain, Belgium.
[Mannebach, S.] Univ Saarlandes Expt, D-66421 Homburg, Germany.
[Mannebach, S.] Klin Pharmakol & Toxikol, D-66421 Homburg, Germany.
[Birnbaumer, L.] NIEHS, Res Triangle Pk, NC 27709 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0028-1298
J9 N-S ARCH PHARMACOL
JI Naunyn-Schmiedebergs Arch. Pharmacol.
PD MAR
PY 2012
VL 385
SU 1
MA 246
BP 57
EP 57
PG 1
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 898YY
UT WOS:000300779500247
ER
PT J
AU Schneider, E
Gao, JL
Holmes, G
Peiper, SC
Murphy, PM
AF Schneider, E.
Gao, J-L
Holmes, G.
Peiper, S. C.
Murphy, P. M.
TI The Duffy Antigen Receptor for Chemokines modulates balance, locomotion
and anxiety-like behavior in mice under homeostatic conditions
SO NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
LA English
DT Meeting Abstract
CT 78th Annual Congress of the
German-Society-for-Experimental-and-Clinical-Pharmacology-and-Toxicology
(DGPT)
CY MAR 19-22, 2012
CL Dresden, GERMANY
SP German Soc Expt & Clin Pharmacol & Toxicol (DGPT)
C1 [Schneider, E.; Gao, J-L; Murphy, P. M.] NIAID, NIH, Mol Signaling Sect, Bethesda, MD 20892 USA.
[Holmes, G.] NIAID, NIH, Inflammat Biol Sect, Bethesda, MD 20892 USA.
[Peiper, S. C.] Jefferson Med Coll Pathol Anat & Cell Biol, Philadelphia, PA 19107 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0028-1298
J9 N-S ARCH PHARMACOL
JI Naunyn-Schmiedebergs Arch. Pharmacol.
PD MAR
PY 2012
VL 385
SU 1
MA 369
BP 84
EP 84
PG 1
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 898YY
UT WOS:000300779500370
ER
PT J
AU Warren, KE
Killian, K
Suuriniemi, M
Wang, YH
Quezado, M
Meltzer, PS
AF Warren, Katherine E.
Killian, Keith
Suuriniemi, Miia
Wang, Yonghong
Quezado, Martha
Meltzer, Paul S.
TI Genomic aberrations in pediatric diffuse intrinsic pontine gliomas
SO NEURO-ONCOLOGY
LA English
DT Article
DE brainstem glioma; DIPG; genomics; microarray; pontine glioma
ID BRAIN-STEM GLIOMA; PHASE-I TRIAL; GROWTH-FACTOR; GENETIC ALTERATIONS;
HYBRIDIZATION; GRADE; GLIOBLASTOMA; TUMOR; ABNORMALITIES; EXPRESSION
AB Diagnostic biopsy is not routinely performed for children with diffuse intrinsic pontine glioma (DIPG). Consequently, our understanding of DIPG biology is hindered by limited tissue availability. We performed comparative genomic hybridization (CGH) on autopsy specimens to examine the feasibility of determining DNA genomic copy number aberrations on formalin-fixed, paraffin-embedded (FFPE) blocks. Histology on FFPE blocks obtained from autopsy of pediatric patients with DIPG was reviewed. Regions were marked for processing, and DNA was extracted from the tissue core, labeled by chemical coupling with Cy5, and hybridized to 105K oligonucleotide CGH arrays. After hybridization and washing, arrays were scanned, and data segmented and processed with Nexus software. Twenty-two samples from 13 subjects were obtained. Histologic variability was noted. CGH was successfully performed on 18 of 22 samples, representing 11 of 13 subjects. All demonstrated DNA copy number abnormalities. High copy number amplification of known oncogenes and homozygous deletions of known tumor suppressor genes were observed. Additional regions of high copy number amplification and homozygous deletion and geographical variations in the CGH patterns were found. CGH performed on FFPE tissue obtained from autopsy yields satisfactory results. This sample set from patients with DIPG was highly informative, with the majority of specimens showing >= 1 abnormality related to a known cancer gene. Aberrations in candidate drug targets were observed. This study establishes the feasibility of genomic DNA analysis from DIPG autopsy material, identifies several targets for which molecular targeted therapy exists, and suggests significant heterogeneity among patients with DIPG.
C1 [Killian, Keith; Suuriniemi, Miia; Wang, Yonghong; Meltzer, Paul S.] NCI, Genet Branch, NIH, Bethesda, MD 20892 USA.
[Quezado, Martha] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA.
[Warren, Katherine E.] NCI, Pediat Oncol Branch, Pediat Neurooncol Sect, Ctr Canc Res,NIH, Bethesda, MD 20892 USA.
RP Warren, KE (reprint author), NCI, Pediat Oncol Branch, Pediat Neurooncol Sect, Ctr Canc Res,NIH, Bldg 10 CRC,Rm 1W-5750, Bethesda, MD 20892 USA.
EM warrenk@mail.nih.gov
FU National Institutes of Health, National Cancer Institute, Center for
Cancer Research
FX This research was supported in part by the Intramural Research Program
of the National Institutes of Health, National Cancer Institute, Center
for Cancer Research.
NR 24
TC 21
Z9 22
U1 0
U2 6
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1522-8517
J9 NEURO-ONCOLOGY
JI Neuro-Oncology
PD MAR
PY 2012
VL 14
IS 3
BP 326
EP 332
DI 10.1093/neuonc/nor190
PG 7
WC Oncology; Clinical Neurology
SC Oncology; Neurosciences & Neurology
GA 900VF
UT WOS:000300918900009
PM 22064882
ER
PT J
AU Yabroff, KR
Harlan, L
Zeruto, C
Abrams, J
Mann, B
AF Yabroff, K. Robin
Harlan, Linda
Zeruto, Christopher
Abrams, Jeffrey
Mann, Bhupinder
TI Patterns of care and survival for patients with glioblastoma multiforme
diagnosed during 2006
SO NEURO-ONCOLOGY
LA English
DT Article
DE brain cancer; glioblastoma; practice patterns; SEER; temozolomide
ID CLINICAL-TRIAL; UNITED-STATES; CANCER; ADULTS; PARTICIPATION;
RADIOTHERAPY; TEMOZOLOMIDE; GLIOMA; TRENDS
AB Standard treatment for glioblastoma multi forme (GBM) changed in 2005 when addition of temozolomide (TMZ) to maximal surgical resection followed by radiation therapy (RT) was shown to prolong survival in a clinical trial. In this study, we assessed treatment patterns and survival of patients with GBM in community settings in the United States. Patients with newly diagnosed GBM who were aged >= 20 years in 2006 (n = 1202) were identified as part of the National Cancer Institute 's Patterns of Care Studies. We assessed treatment patterns, and in the subset of patients who received total or partial surgical resection, we used multivariable regression analysis to assess patient, clinical, and health system factors associated with receipt of adjuvant chemotherapy and RT and survival through 2008. Approximately 65% of patients with GBM received total or partial surgical resection, and approximately 70% of these patients received adjuvant TMZ and RT. Receipt of adjuvant therapy was associated with patient age, marital status, health insurance, and tumor location. Median survival in all patients was 10 months (95% confidence interval [CI], 9-11 months). Receipt of adjuvant therapy following resection was associated with a lower risk of dying in adjusted analyses for patients who received TMZ and RT (hazard ratio [HR], 0.25; 95% CI, 0.18-0.35) and other adjuvant therapies (HR, 0.55; 95% CI, 0.37-0.81), compared with no adjuvant therapy. We observed rapid diffusion of a new standard of treatment, adjuvant and concurrent TMZ with RT, among adult patients with newly diagnosed GBM in the community setting following publication of a pivotal clinical trial.
C1 [Yabroff, K. Robin] NCI, Hlth Serv & Econ Branch, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Zeruto, Christopher] Informat Management Serv Inc, Silver Spring, MD USA.
[Abrams, Jeffrey; Mann, Bhupinder] NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA.
RP Yabroff, KR (reprint author), NCI, Hlth Serv & Econ Branch, Appl Res Program, Div Canc Control & Populat Sci, Execut Plaza N,Rm 4005,6130 Execut Blvd,MSC 7344, Bethesda, MD 20892 USA.
EM yabroffr@mail.nih.gov
OI Yabroff, K. Robin/0000-0003-0644-5572
FU National Cancer Institute [N01-PC35133, N01-PC-35135, N01-PC-35141,
N01-PC35136, N01-PC-35137, N01-PC-35138, N01-PC35139, N01-PC-35142,
N01-PC-35143, N01-PC35145, N01-PC-54402, N01-PC-54403, N01-PC54404,
N01-PC-54405]
FX This work was supported by the following grants provided by the National
Cancer Institute N01-PC35133, N01-PC-35135, N01-PC-35141, N01-PC35136,
N01-PC-35137, N01-PC-35138, N01-PC35139, N01-PC-35142, N01-PC-35143,
N01-PC35145, N01-PC-54402, N01-PC-54403, N01-PC54404, and N01-PC-54405.
NR 28
TC 27
Z9 29
U1 0
U2 2
PU OXFORD UNIV PRESS INC
PI CARY
PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA
SN 1522-8517
J9 NEURO-ONCOLOGY
JI Neuro-Oncology
PD MAR
PY 2012
VL 14
IS 3
BP 351
EP 359
DI 10.1093/neuonc/nor218
PG 9
WC Oncology; Clinical Neurology
SC Oncology; Neurosciences & Neurology
GA 900VF
UT WOS:000300918900012
PM 22241797
ER
PT J
AU Chen, MF
Huang, YC
Long, C
Yang, HI
Lee, HC
Chen, PY
Hoffer, BJ
Lee, TJF
AF Chen, Mei-Fang
Huang, Yi-Chiao
Long, Cheng
Yang, Hui-I
Lee, Hui-Chao
Chen, Po-Yi
Hoffer, Barry J.
Lee, Tony Jer-Fu
TI Bimodal effects of fluoxetine on cerebral nitrergic neurogenic
vasodilation in porcine large cerebral arteries
SO NEUROPHARMACOLOGY
LA English
DT Article
DE Fluoxetine; Antidepressant; Neurogenic nitrergic vasodilation; Porcine
basilar artery; Nicotinic acetylcholine receptor; Nitric oxide
ID NICOTINIC ACETYLCHOLINE-RECEPTORS; NITRIC OXIDERGIC INNERVATION;
LIQUID-CHROMATOGRAPHY; UPTAKE INHIBITORS; CALCIUM-CHANNELS; MONOAMINE
UPTAKE; BLOOD-FLOW; SEROTONIN; MUSCLE; NORFLUOXETINE
AB Fluoxetine-induced relaxation of the smooth muscle of small cerebral arteries is thought beneficial in treating mental disorders. The present study was designed to examine effect of fluoxetine on neurogenic nitrergic vasodilation in large cerebral arteries, using in vitro tissue myography, techniques of electrophysiology, calcium imaging and biochemistry. In isolated porcine endothelium-denuded basilar arteries in the presence of U-46619-induced active muscle tone, fluoxetine in low concentration (<0.03 mu M) significantly enhanced nicotine- and choline-induced relaxations. The vasorelaxation, however, was blocked by higher concentration of fluoxetine (>0.3 mu M) with maximum inhibition at 3 mu M. At this concentration, fluoxetine did not affect the basal tone or vasorelaxations induced by transmural nerve stimulation, sodium nitroprusside, or isoproterenol. Furthermore, fluoxetine exclusively blocked nicotine-induced inward currents and calcium influx in cultured neurons of rat superior cervical ganglion and Xenopus oocytes expressing human alpha 7-, alpha 3 beta 2-, or alpha 4 beta 2-nicotinic acetylcholine receptors (nAChRs). In addition, fluoxetine at 0.03 mu M and 3 mu M significantly enhanced and blocked, respectively, nicotine-induced norepinephrine (NE) release from cerebral perivascular sympathetic nerves. These results indicate that fluoxetine via axo-axonal interaction mechanism exhibits bimodal effects on nAChR-mediated neurogenic nitrergic dilation of basilar arteries. Fluoxetine in high concentrations decreases while in low concentrations it increases neurogenic vasodilation. These results from in vitro experimentation suggest that optimal concentrations of fluoxetine which increase or minimally affect neurogenic vasodilation indicative of regional cerebral blood flow may be important consideration in treating mental disorders. (c) 2011 Elsevier Ltd. All rights reserved.
C1 [Lee, Tony Jer-Fu] Tzu Chi Univ, Coll Life Sci, Dept Life Sci, Hualien 970, Taiwan.
[Chen, Mei-Fang; Yang, Hui-I; Chen, Po-Yi] Buddhist Tzu Chi Gen Hosp, Dept Res, Hualien, Taiwan.
[Chen, Mei-Fang] Tzu Chi Coll Technol, Hualien, Taiwan.
[Lee, Hui-Chao; Lee, Tony Jer-Fu] Tzu Chi Univ, Inst Med Sci, Hualien 970, Taiwan.
[Huang, Yi-Chiao; Chen, Po-Yi; Lee, Tony Jer-Fu] Tzu Chi Univ, Coll Med, Inst Pharmacol & Toxicol, Hualien 970, Taiwan.
[Chen, Mei-Fang; Lee, Hui-Chao; Chen, Po-Yi; Lee, Tony Jer-Fu] Tzu Chi Univ, Ctr Vasc Med, Hualien 970, Taiwan.
[Hoffer, Barry J.] NIDA, NIH, Baltimore, MD USA.
[Long, Cheng; Lee, Tony Jer-Fu] So Illinois Univ, Sch Med, Dept Pharmacol, Springfield, IL 62794 USA.
RP Lee, TJF (reprint author), Tzu Chi Univ, Coll Life Sci, Dept Life Sci, 701 Sec 3,Chung Yang Rd, Hualien 970, Taiwan.
EM tlee@mail.tcu.edu.tw
OI Lee, Reggie/0000-0001-6099-8333
FU Taiwan National Science Council [NSC 95-2314-B-303-014-MY3,
NSC-95-2320-B-320-013-MY2, NSC-96-2320-B-320-005-MY3, NSC
100-2320-B-320-007-MY2]; Tzu Chi University [TCRPP99006,
TCIRP98005-01Y1, TCIRP98005-01Y2]
FX We thank Dr. J. Michael McIntosh of university of Utah for the generous
gift of alpha 3 beta 2-nAChR plasmids, Dr. Jon-Son Kuo for reading the
manuscript, Mr. Wen-Hao Lan and Ms. Wan-Rong Lin for technical
assistance, and Fong-Ling packing company for supplying porcine brains.
This work was supported by the grants from Taiwan National Science
Council [NSC 95-2314-B-303-014-MY3, NSC-95-2320-B-320-013-MY2,
NSC-96-2320-B-320-005-MY3 and NSC 100-2320-B-320-007-MY2], and Tzu Chi
University (TCRPP99006, TCIRP98005-01Y1, and TCIRP98005-01Y2).
NR 46
TC 3
Z9 3
U1 0
U2 3
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 MAR
PY 2012
VL 62
IS 4
BP 1651
EP 1658
DI 10.1016/j.neuropharm.2011.11.011
PG 8
WC Neurosciences; Pharmacology & Pharmacy
SC Neurosciences & Neurology; Pharmacology & Pharmacy
GA 904TT
UT WOS:000301221500006
PM 22155207
ER
PT J
AU Guo, JD
Hazra, R
Dabrowska, J
Muly, EC
Wess, J
Rainnie, DG
AF Guo, Ji-Dong
Hazra, Rimi
Dabrowska, Joanna
Muly, E. Chris
Wess, Juergen
Rainnie, Donald G.
TI Presynaptic muscarinic M-2 receptors modulate glutamatergic transmission
in the bed nucleus of the stria terminalis
SO NEUROPHARMACOLOGY
LA English
DT Article
DE Acetylcholine; Eserine; Carbachol; Muscarinic receptor knockout mice;
EPSCs
ID LONG-TERM POTENTIATION; SYNAPTIC-TRANSMISSION; ACETYLCHOLINE-RECEPTORS;
RAT-BRAIN; CHOLINERGIC MODULATION; PREFRONTAL CORTEX; BASAL FOREBRAIN;
KNOCKOUT MICE; IN-VIVO; HIPPOCAMPAL ACETYLCHOLINE
AB The anterolateral cell group of the bed nucleus of the stria terminalis (BNSTALG) serves as an important relay station in stress circuitry. Limbic inputs to the BNSTALG are primarily glutamatergic and activity-dependent changes in this input have been implicated in abnormal behaviors associated with chronic stress and addiction. Significantly, local infusion of acetylcholine (ACh) receptor agonists into the BNST trigger stress-like cardiovascular responses, however, little is known about the effects of these agents on glutamatergic transmission in the BNSTALG. Here, we show that glutamate- and ACh-containing fibers are found in close association in the BNSTALG. Moreover, in the presence of the acetylcholinesterase inhibitor, eserine, endogenous ACh release evoked a long-lasting reduction of the amplitude of stimulus-evoked EPSCs. This effect was mimicked by exogenous application of the ACh analog, carbachol, which caused a reversible, dose-dependent, reduction of the evoked EPSC amplitude, and an increase in both the paired-pulse ratio and coefficient of variation, suggesting a presynaptic site of action. Uncoupling of postsynaptic G-proteins with intracellular GDP-beta-S, or application of the nicotinic receptor antagonist, tubocurarine, failed to block the carbachol effect. In contrast, the carbachol effect was blocked by prior application of atropine or M-2 receptor-preferring antagonists, and was absent in M-2/M-4 receptor knockout mice, suggesting that presynaptic M-2 receptors mediate the effect of ACh. Immunoelectron microscopy studies further revealed the presence of M-2 receptors on axon terminals that formed asymmetric synapses with BNST neurons. Our findings suggest that presynaptic M-2 receptors might be an important modulator of the stress circuit and hence a novel target for drug development. (c) 2011 Elsevier Ltd. All rights reserved.
C1 [Guo, Ji-Dong; Hazra, Rimi; Dabrowska, Joanna; Rainnie, Donald G.] Yerkes Natl Primate Res Ctr, Div Behav Neurosci & Psychiat Disorders, Atlanta, GA 30329 USA.
[Guo, Ji-Dong; Hazra, Rimi; Dabrowska, Joanna; Muly, E. Chris; Rainnie, Donald G.] Emory Univ, Dept Psychiat & Behav Sci, Atlanta, GA 30322 USA.
[Muly, E. Chris] Yerkes Natl Primate Res Ctr, Div Neuropharmacol & Neurol Dis, Atlanta, GA 30329 USA.
[Muly, E. Chris] Vet Affairs Med Ctr, Atlanta Dept, Decatur, GA 30033 USA.
[Wess, Juergen] NIDDK, Mol Signaling Sect, Bioorgan Chem Lab, NIH, Bethesda, MD USA.
RP Rainnie, DG (reprint author), Yerkes Natl Primate Res Ctr, Div Behav Neurosci & Psychiat Disorders, Yerkes Neurosci Bldg,Rm 5220 954, Atlanta, GA 30329 USA.
EM drainni@emory.edu
RI Guo, Jidong/D-5564-2009; Rainnie, Donald/L-3853-2016
OI Rainnie, Donald/0000-0003-0758-0530
FU National Institute of Mental Health [MH-072908]; Yerkes National Primate
Research Center [RR-00165]; National Institutes of Health
FX The authors want to thank Dr. Allan Levey for constructive comments and
help in supplying the knockout mice and Marcelia Maddox for technical
assistance in EM studies. This work was supported by National Institute
of Mental Health Grant MH-072908 to D. G. Rainnie; and the Yerkes
National Primate Research Center Base Grant RR-00165 awarded by the
Animal Resources Program of National Institutes of Health.
NR 86
TC 7
Z9 7
U1 1
U2 5
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 MAR
PY 2012
VL 62
IS 4
BP 1671
EP 1683
DI 10.1016/j.neuropharm.2011.11.013
PG 13
WC Neurosciences; Pharmacology & Pharmacy
SC Neurosciences & Neurology; Pharmacology & Pharmacy
GA 904TT
UT WOS:000301221500008
PM 22166222
ER
PT J
AU Carcillo, JA
Dean, JM
Holubkov, R
Berger, J
Meert, KL
Anand, KJS
Zimmerman, J
Newth, CJL
Harrison, R
Burr, J
Willson, DF
Nicholson, C
AF Carcillo, Joseph A.
Dean, J. Michael
Holubkov, Richard
Berger, John
Meert, Kathleen L.
Anand, K. J. S.
Zimmerman, Jerry
Newth, Christopher J. L.
Harrison, Rick
Burr, Jeri
Willson, Douglas F.
Nicholson, Carol
CA Eunice Kennedy Shriver Natl Inst
TI The randomized comparative pediatric critical illness stress-induced
immune suppression (CRISIS) prevention trial
SO PEDIATRIC CRITICAL CARE MEDICINE
LA English
DT Article
DE glutamine; nosocomial infection; prolactin; selenium; sepsis; whey
protein; zinc
ID WHEY-PROTEIN CONCENTRATE; ENRICHED ENTERAL NUTRITION; PLASMA GLUTATHIONE
LEVELS; ORAL REHYDRATION THERAPY; HIV-INFECTED PATIENTS; DOUBLE-BLIND;
AMINO-ACIDS; ZINC SUPPLEMENTATION; SUCKLING RATS; CHILDREN
AB Objectives: Nosocomial infection/sepsis occurs in up to 40% of children requiring long-term intensive care. Zinc, selenium, glutamine, metoclopramide (a prolactin secretalogue), and/or whey protein supplementation have been effective in reducing infection and sepsis in other populations. We evaluated whether daily nutriceutical supplementation with zinc, selenium, glutamine, and metoclopramide, compared to whey protein, would reduce the occurrence of nosocomial infection/sepsis in this at-risk population.
Design: Randomized, double-blinded, comparative effectiveness trial.
Setting: Eight pediatric intensive care units in the National Institutes of Child Health and Human Development Collaborative Pediatric Critical Care Research Network.
Patients: Two hundred ninety-three long-term intensive care patients (age 1-17 yrs) expected to require >72 hrs of invasive care.
Interventions: Patients were stratified according to immuno-compromised status and center and then were randomly assigned to receive daily enteral zinc, selenium, glutamine, and intravenous metoclopramide (n = 149), or daily enteral whey protein (n = 144) and intravenous saline for up to 28 days of intensive care unit stay. The primary end point was time to development of nosocomial sepsis/infection. The analysis was intention to treat.
Measurements and Main Results: There were no differences by assigned treatment in the overall population with respect to time until the first episode of nosocomial infection/sepsis (median whey protein 13.2 days vs. zinc, selenium, glutamine, and intravenous metoclopramide 12.1 days; p = .29 by log-rank test) or the rate of nosocomial infection/sepsis (4.83/100 days whey protein vs. 4.99/100 days zinc, selenium, glutamine, and intravenous metoclopramide; p = .81). Only 9% of the 293 subjects were immunocompromised and there was a reduction in rate of nosocomial infection/sepsis with zinc, selenium, glutamine, and intravenous metoclopramide in this immunocompromised group (6.09/100 days whey protein vs. 1.57/100 days zinc, selenium, glutamine, and intravenous metoclopramide; p = .011).
Conclusion: Compared with whey protein supplementation, zinc, selenium, glutamine, and intravenous metoclopramide conferred no advantage in the immune-competent population. Further evaluation of zinc, selenium, glutamine, and intravenous metoclopramide supplementation is warranted in the immunocompromised long-term pediatric intensive care unit patient. (Pediatr Crit Care Med 2012; 13: 165-173)
C1 [Carcillo, Joseph A.] UPMC, Childrens Hosp Pittsburgh, Pittsburgh, PA USA.
[Dean, J. Michael; Holubkov, Richard; Berger, John] Univ Utah, Salt Lake City, UT USA.
[Berger, John] Childrens Natl Med Ctr, Washington, DC 20010 USA.
[Meert, Kathleen L.] Childrens Hosp Michigan, Detroit, MI 48201 USA.
[Anand, K. J. S.] Arkansas Childrens Hosp, Little Rock, AR 72202 USA.
[Zimmerman, Jerry] Seattle Childrens Hosp, Seattle, WA USA.
[Newth, Christopher J. L.] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA.
[Holubkov, Richard] Mattel Childrens Hosp, Los Angeles, CA USA.
[Willson, Douglas F.] Univ Virginia, Childrens Hosp, Charlottesville, VA USA.
[Nicholson, Carol] NICHHD, Bethesda, MD 20892 USA.
RP Carcillo, JA (reprint author), UPMC, Childrens Hosp Pittsburgh, Pittsburgh, PA USA.
EM carcilloja@ccm.upmc.edu
RI Andrade, Hugo/M-6631-2013;
OI Andrade, Hugo/0000-0001-6781-6125; Anand, Kanwaljeet/0000-0001-6498-1483
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development (NICHD), National Institutes of Health (NIH), Department of
Health and Human Services (DHHS) [U10HD050096, U10HD049981, U10HD500009,
U10HD049945, U10HD049983, U10HD050012, U01HD049934]
FX Supported, in part, by the following cooperative agreements from the
Eunice Kennedy Shriver National Institute of Child Health and Human
Development (NICHD), National Institutes of Health (NIH), Department of
Health and Human Services (DHHS; U10HD050096, U10HD049981, U10HD500009,
U10HD049945, U10HD049983, U10HD050012, and U01HD049934).
NR 30
TC 32
Z9 34
U1 0
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1529-7535
J9 PEDIATR CRIT CARE ME
JI Pediatr. Crit. Care Med.
PD MAR
PY 2012
VL 13
IS 2
BP 165
EP 173
DI 10.1097/PCC.0b013e31823896ae
PG 9
WC Critical Care Medicine; Pediatrics
SC General & Internal Medicine; Pediatrics
GA 904WR
UT WOS:000301230100019
PM 22079954
ER
PT J
AU Tykvart, J
Sacha, P
Barinka, C
Knedlik, T
Starkova, J
Lubkowski, J
Konvalinka, J
AF Tykvart, J.
Sacha, P.
Barinka, C.
Knedlik, T.
Starkova, J.
Lubkowski, J.
Konvalinka, J.
TI Efficient and versatile one-step affinity purification of in vivo
biotinylated proteins: Expression, characterization and structure
analysis of recombinant human glutamate carboxypeptidase II
SO PROTEIN EXPRESSION AND PURIFICATION
LA English
DT Article
DE Affinity purification; Biotin acceptor peptide; Recombinant protein
expression; Biotin-protein ligase (BirA); Co-localization; PSMA
ID LINKED ACIDIC DIPEPTIDASE; MEMBRANE ANTIGEN PSMA; SUBSTRATE-SPECIFICITY;
MONOMERIC STREPTAVIDIN; ENZYMATIC SYNTHESIS; PROSTATE-CANCER; TRANSGENIC
MICE; STREP-TAG; SITE; HOLOTRANSCARBOXYLASE
AB Affinity purification is a useful approach for purification of recombinant proteins. Eukaryotic expression systems have become more frequently used at the expense of prokaryotic systems since they afford recombinant eukaryotic proteins with post-translational modifications similar or identical to the native ones.
Here, we present a one-step affinity purification set-up suitable for the purification of secreted proteins. The set-up is based on the interaction between biotin and mutated streptavidin. Drosophila Schneider 2 cells are chosen as the expression host, and a biotin acceptor peptide is used as an affinity tag. This tag is biotinylated by Escherichia coli biotin-protein ligase in vivo. We determined that localization of the ligase within the ER led to the most effective in vivo biotinylation of the secreted proteins. We optimized a protocol for large-scale expression and purification of AviTEV-tagged recombinant human glutamate carboxypeptidase II (Avi-GCPII) with milligram yields per liter of culture. We also determined the 3D structure of Avi-GCPII by X-ray crystallography and compared the enzymatic characteristics of the protein to those of its non-tagged variant. These experiments confirmed that AviTEV tag does not affect the biophysical properties of its fused partner.
Purification approach, developed here, provides not only a sufficient amount of highly homogenous protein but also specifically and effectively biotinylates a target protein and thus enables its subsequent visualization or immobilization. (C) 2011 Elsevier Inc. All rights reserved.
C1 [Konvalinka, J.] ASCR, Inst Organ Chem & Biochem, Vvi, Gilead Sci & IOCB Res Ctr, Prague 16610 6, Czech Republic.
[Tykvart, J.; Sacha, P.; Knedlik, T.; Konvalinka, J.] Charles Univ Prague, Dept Biochem, Fac Nat Sci, Prague 2, Czech Republic.
[Barinka, C.] Acad Sci Czech Republic, Inst Biotechnol, Prague 4, Czech Republic.
[Lubkowski, J.] NCI, Ctr Canc Res, Frederick, MD 21701 USA.
RP Konvalinka, J (reprint author), ASCR, Inst Organ Chem & Biochem, Vvi, Gilead Sci & IOCB Res Ctr, Flemingovo 2, Prague 16610 6, Czech Republic.
EM jan.konvalinka@uochb.cas.cz
RI Tykvart, Jan/G-6770-2014; Konvalinka, Jan/G-7518-2014; Knedlik,
Tomas/G-7955-2014; Sacha, Pavel/G-9729-2014; Barinka, Cyril/G-9803-2014;
OI Tykvart, Jan/0000-0002-6938-1513; Sacha, Pavel/0000-0001-6198-9826;
Konvalinka, Jan/0000-0003-0695-9266
FU Ministry of Education of Czech Republic [Z4 055 905, 1M0508, LC 512,
1978]; IBT [AV0Z50520701]; Guilford Pharmaceuticals; NIH; National
Cancer Institute; Center for Cancer Research; US Department of Energy,
Office of Science, Office of Basic Energy Sciences [W-31-109-Eng38]
FX This work (performed under the research project Z4 055 905) was
supported by Grants 1M0508 and LC 512 from the Ministry of Education of
Czech Republic, EMBO Installation Grant #1978 (C.B), the IBT
institutional support (AV0Z50520701), by research support from Guilford
Pharmaceuticals, and in part by the Intramural Research Program of the
NIH, National Cancer Institute, Center for Cancer Research (J.L.). Use
of the Advanced Photon Source was supported by the US Department of
Energy, Office of Science, Office of Basic Energy Sciences, under
Contract No. W-31-109-Eng38.
NR 43
TC 13
Z9 14
U1 0
U2 13
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 1046-5928
EI 1096-0279
J9 PROTEIN EXPRES PURIF
JI Protein Expr. Purif.
PD MAR
PY 2012
VL 82
IS 1
BP 106
EP 115
DI 10.1016/j.pep.2011.11.016
PG 10
WC Biochemical Research Methods; Biochemistry & Molecular Biology;
Biotechnology & Applied Microbiology
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology
GA 900WZ
UT WOS:000300923700016
PM 22178733
ER
PT J
AU Austin, BP
Waugh, DS
AF Austin, Brian P.
Waugh, David S.
TI Isolation of Metarhizium anisopliae carboxypeptidase A with native
disulfide bonds from the cytosol of Escherichia coli BL21(DE3)
SO PROTEIN EXPRESSION AND PURIFICATION
LA English
DT Article
DE MeCPA; Carboxypeptidase; Maltose-binding protein; Polyhistidine tag;
Thermolysin; His-tag; DsbC; DsbA; Protein disulfide isomerase; trxB; gor
ID MALTOSE-BINDING PROTEIN; HPV E6 ONCOPROTEIN; AFFINITY TAGS;
SUBSTRATE-SPECIFICITY; RECOMBINANT PROTEINS; HEXAHISTIDINE-TAG;
INCLUSION-BODIES; FUSION PROTEINS; HIS-TAG; EXPRESSION
AB The carboxypeptidase A enzyme from Metarhizium anisopliae (MeCPA) has broader specificity than the mammalian A-type carboxypeptidases, making it a more useful reagent for the removal of short affinity tags and disordered residues from the C-termini of recombinant proteins. When secreted from baculovirus-infected insect cells, the yield of pure MeCPA was 0.25 mg per liter of conditioned medium. Here, we describe a procedure for the production of MeCPA in the cytosol of Escherichia coli that yields approximately 0.5 mg of pure enzyme per liter of cell culture. The bacterial system is much easier to scale up and far less expensive than the insect cell system. The expression strategy entails maintaining the proMeCPA zymogen in a soluble state by fusing it to the C-terminus of maltose-binding protein (MBP) while simultaneously overproducing the protein disulfide isomerase DsbC in the cytosol from a separate plasmid. Unexpectedly, we found that the yield of active and properly oxidized MeCPA was highest when coexpressed with DsbC in BL21(DE3) cells that do not also contain mutations in the trxB and gor genes. Moreover, the formation of active MeCPA was only partially dependent on the disulfide-isomerase activity of DsbC. Intriguingly, we observed that most of the active MeCPA was generated after cell lysis and amylose affinity purification of the MBP-proMeCPA fusion protein, during the time that the partially purified protein was held overnight at 4 degrees C prior to activation with thermolysin. Following removal of the MBP-propeptide by thermolysin digestion, active MeCPA (with a C-terminal polyhistidine tag) was purified to homogeneity by immobilized metal affinity chromatography (IMAC), ion exchange chromatography and gel filtration. Published by Elsevier Inc.
C1 [Austin, Brian P.; Waugh, David S.] NCI, Prot Engn Sect, Macromol Crystallog Lab, Ctr Canc Res, Frederick, MD 21702 USA.
RP Waugh, DS (reprint author), NCI, Prot Engn Sect, Macromol Crystallog Lab, Ctr Canc Res, POB B, Frederick, MD 21702 USA.
EM waughd@mail.nih.gov
FU National Institutes of Health, National Cancer Institute, Center for
Cancer Research
FX We thank Dr. Joseph E. Tropea for the suggestion to try co-expression of
the MeCPA fusion protein and DsbC in BL-21(DE3) cells lacking the trxB
and gor mutations. This project was supported by the Intramural Research
Program of the National Institutes of Health, National Cancer Institute,
Center for Cancer Research. The content of this publication does not
necessarily reflect the views or policies of the Department of Health
and Human Services, nor does the mention of trade names, commercial
products or organizations imply endorsement by the US government. We
thank the Biophysics Resource in the Structural Biophysics Laboratory,
NCl-Frederick, for use of the LC/ESMS instrument.
NR 38
TC 7
Z9 7
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 1046-5928
J9 PROTEIN EXPRES PURIF
JI Protein Expr. Purif.
PD MAR
PY 2012
VL 82
IS 1
BP 116
EP 124
DI 10.1016/j.pep.2011.11.015
PG 9
WC Biochemical Research Methods; Biochemistry & Molecular Biology;
Biotechnology & Applied Microbiology
SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology
GA 900WZ
UT WOS:000300923700017
PM 22197595
ER
PT J
AU Amos, A
Greaves, L
Nichter, M
Bloch, M
AF Amos, Amanda
Greaves, Lorraine
Nichter, Mimi
Bloch, Michele
TI Women and tobacco: a call for including gender in tobacco control
research, policy and practice
SO TOBACCO CONTROL
LA English
DT Article
ID SECONDHAND SMOKE EXPOSURE; COLLEGE-STUDENTS; SEX-DIFFERENCES;
YOUNG-PEOPLE; PREGNANCY; CESSATION; NICOTINE; HEALTH; GIRLS; COUNTRIES
AB Objectives Female smoking is predicted to double between 2005 and 2025. There have been numerous calls for action on women's tobacco use over the past two decades. In the present work, evidence about female tobacco use, progress, challenges and ways forward for developing gendered tobacco control is reviewed.
Methods Literature on girls, women and tobacco was reviewed to identify trends and determinants of tobacco use and exposure, the application of gender analysis, tobacco marketing, the impact of tobacco control on girls and women and ways to address these issues particularly in low-income and middle-income countries.
Results Global female tobacco use is increasingly complex, involving diverse products and factors including tobacco marketing, globalisation and changes in women's status. In high-income countries female smoking is declining but is increasingly concentrated among disadvantaged women. In low-income and middle-income countries the pattern is more complex; in several regions the gap between girls' and boys' smoking is narrow. Gendered analyses and approaches to tobacco control are uncommon, especially in low-income and middle-income countries.
Conclusions Tobacco control has remained largely gender blind, with little recognition of the importance of understanding the context and challenges of girl's and women's smoking and secondhand smoke exposure. There has been little integration of gender considerations in research, policy and programmes. The present work makes a case for gender and diversity analyses in tobacco control to reflect and identify intersecting factors affecting women's tobacco use. This will help animate the WHO Framework Convention on Tobacco Control's concern for gender specificity and women's leadership, and reduce the impact of tobacco on women.
C1 [Amos, Amanda] Univ Edinburgh, Sch Med, Ctr Populat Hlth Sci, UK Ctr Tobacco Control Studies, Edinburgh EH8 9AG, Midlothian, Scotland.
[Greaves, Lorraine] Univ British Columbia, Fac Med, Sch Populat & Publ Hlth, British Columbia Ctr Excellence Womens Hlth, Vancouver, BC, Canada.
[Nichter, Mimi] Univ Arizona, Sch Anthropol, Tucson, AZ USA.
[Bloch, Michele] US Natl Canc Inst, Tobacco Control Res Branch, Rockville, MD USA.
RP Amos, A (reprint author), Univ Edinburgh, Sch Med, Ctr Populat Hlth Sci, UK Ctr Tobacco Control Studies, Teviot Pl, Edinburgh EH8 9AG, Midlothian, Scotland.
EM amanda.amos@ed.ac.uk
FU UKCTCS, a UKCRC Public Health Research Centre of Excellence; British
Heart Foundation; Cancer Research UK; Economic and Social Research
Council; Medical Research Council; Department of Health under UK
Clinical Research Collaboration
FX We thank Irina Morozova, Svitlana Sydorova, Magdalena Petryniak, Andriy
Skipalskyi and Martina Potschke-Langer for providing pictures of tobacco
promotions and product. Amanda Amos is part funded by the UKCTCS, a
UKCRC Public Health Research Centre of Excellence. Funding from British
Heart Foundation, Cancer Research UK, Economic and Social Research
Council, Medical Research Council, and the Department of Health, under
the auspices of the UK Clinical Research Collaboration is gratefully
acknowledged.
NR 105
TC 64
Z9 65
U1 1
U2 19
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 MAR
PY 2012
VL 21
IS 2
BP 236
EP 243
DI 10.1136/tobaccocontrol-2011-050280
PG 8
WC Public, Environmental & Occupational Health
SC Public, Environmental & Occupational Health
GA 897CG
UT WOS:000300618200038
PM 22166266
ER
PT J
AU Tucker, JD
Chen, AH
Glass, RI
AF Tucker, Joseph D.
Chen, Alice H.
Glass, Roger I.
TI Foreign Language Assessment and Training in U.S. Medical Education Is a
Must
SO ACADEMIC MEDICINE
LA English
DT Letter
C1 [Tucker, Joseph D.] Harvard Univ, Sch Med, Boston, MA 02215 USA.
[Chen, Alice H.] Univ Calif San Francisco, Sch Med, Dept Med, San Francisco, CA USA.
[Glass, Roger I.] NIH, Fogarty Int Ctr, Bethesda, MD USA.
RP Tucker, JD (reprint author), Harvard Univ, Sch Med, Boston, MA 02215 USA.
EM joseph.tucker@post.harvard.edu
RI liu, jing/D-9482-2012
NR 3
TC 1
Z9 1
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1040-2446
J9 ACAD MED
JI Acad. Med.
PD MAR
PY 2012
VL 87
IS 3
BP 257
EP 257
DI 10.1097/ACM.0b013e3182447096
PG 1
WC Education, Scientific Disciplines; Health Care Sciences & Services
SC Education & Educational Research; Health Care Sciences & Services
GA 901TK
UT WOS:000300989500007
PM 22373612
ER
PT J
AU Ray, LA
Barr, CS
Blendy, JA
Oslin, D
Goldman, D
Anton, RF
AF Ray, Lara A.
Barr, Christina S.
Blendy, Julie A.
Oslin, David
Goldman, David
Anton, Raymond F.
TI The Role of the Asn40Asp Polymorphism of the Mu Opioid Receptor Gene
(OPRM1) on Alcoholism Etiology and Treatment: A Critical Review
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Review
DE OPRM1; Pharmacogenetics; Genetics; Alcoholism; Naltrexone; Asn40Asp
ID SINGLE-NUCLEOTIDE POLYMORPHISM; HPA-AXIS ACTIVATION; FUNCTIONAL
POLYMORPHISM; SUBSTANCE DEPENDENCE; A118G POLYMORPHISM; HEAVY DRINKERS;
DRUG-DEPENDENCE; SUBJECTIVE RESPONSES; NALTREXONE TREATMENT;
NATURAL-ENVIRONMENT
AB The endogenous opioid system has been implicated in the pathophysiology of alcoholism as it modulates the neurobehavioral effects of alcohol. A variant in the mu opioid receptor gene (OPRM1), the Asn40Asp polymorphism, has received attention as a functional variant that may influence a host of behavioral phenotypes for alcoholism as well as clinical response to opioid antagonists. This paper will review converging lines of evidence on the effect of the Asn40Asp SNP on alcoholism phenotypes, including: (i) genetic association studies; (ii) behavioral studies of alcoholism; (iii) neuroimaging studies; (iv) pharmacogenetic studies and clinical trials; and (v) preclinical animal studies. Together, these lines of research seek to elucidate the effects of this functional polymorphism on alcoholism etiology and treatment response.
C1 [Ray, Lara A.] Univ Calif Los Angeles, Dept Psychol, Los Angeles, CA 90095 USA.
[Barr, Christina S.] NIAAA, Lab Clin & Translat Studies, Bethesda, MD USA.
[Blendy, Julie A.] Univ Penn, Dept Pharmacol, Sch Med, Philadelphia, PA 19104 USA.
[Goldman, David] NIAAA, Neurogenet Lab, Bethesda, MD USA.
[Anton, Raymond F.] Med Univ S Carolina, Ctr Drug & Alcohol Programs, Charleston, SC 29425 USA.
RP Ray, LA (reprint author), Univ Calif Los Angeles, Dept Psychol, 1285 Franz Hall,POB 951563, Los Angeles, CA 90095 USA.
EM lararay@psych.ucla.edu
RI Goldman, David/F-9772-2010
OI Goldman, David/0000-0002-1724-5405
FU Intramural NIH HHS [Z01 AA000301-09, Z01 AA000301-10, ZIA AA000306-04];
NIAAA NIH HHS [K05 AA017435, R01 AA017633]
NR 84
TC 36
Z9 37
U1 1
U2 8
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD MAR
PY 2012
VL 36
IS 3
BP 385
EP 394
DI 10.1111/j.1530-0277.2011.01633.x
PG 10
WC Substance Abuse
SC Substance Abuse
GA 897PC
UT WOS:000300663900001
PM 21895723
ER
PT J
AU Litten, RZ
Fertig, JB
Falk, DE
Ryan, ML
Mattson, ME
Collins, JF
Murtaugh, C
Ciraulo, D
Green, AI
Johnson, B
Pettinati, H
Swift, R
Afshar, M
Brunette, MF
Tiouririne, NAD
Kampman, K
Stout, R
AF Litten, Raye Z.
Fertig, Joanne B.
Falk, Daniel E.
Ryan, Megan L.
Mattson, Margaret E.
Collins, Joseph F.
Murtaugh, Cristin
Ciraulo, Domenic
Green, Alan I.
Johnson, Bankole
Pettinati, Helen
Swift, Robert
Afshar, Maryam
Brunette, Mary F.
Tiouririne, Nassima A. -D.
Kampman, Kyle
Stout, Robert
CA NCIG 001 Study Grp
TI A Double-Blind, Placebo-Controlled Trial to Assess the Efficacy of
Quetiapine Fumarate XR in Very Heavy-Drinking Alcohol-Dependent Patients
SO ALCOHOLISM-CLINICAL AND EXPERIMENTAL RESEARCH
LA English
DT Article
DE Alcohol Dependence; Quetiapine; Seroquel (R); Medications Development;
Alcohol Use Disorder
ID RANDOMIZED CONTROLLED-TRIAL; USE DISORDERS; SCALE; SCHIZOPHRENIA;
ARIPIPRAZOLE; CONSUMPTION; DEPRESSION; OLANZAPINE; SLEEP; QUESTIONNAIRE
AB Background: Despite advances in developing medications to treat alcohol dependence, few such medications have been approved by the Food and Drug Administration. Identified molecular targets are encouraging and can lead to the development and testing of new compounds. Atypical antipsychotic medications have been explored with varying results. Prior research suggests that the antipsychotic quetiapine may be beneficial in an alcohol-dependent population of very heavy drinkers.
Methods: In this double-blind, placebo-controlled trial, 224 alcohol-dependent patients who reported very heavy drinking were recruited across 5 clinical sites. Patients received either quetiapine or placebo and Medical Management behavioral intervention. Patients were stratified on gender, clinical site, and reduction in drinking prior to randomization.
Results: No differences between the quetiapine and placebo groups were detected in the primary outcome, percentage heavy-drinking days, or other drinking outcomes. Quetiapine significantly reduced depressive symptoms and improved sleep but had no effect on other nondrinking outcomes. Results from a subgroup analysis suggest that patients who reduced their drinking prior to randomization had significantly better drinking outcomes during the maintenance phase (p < 0.0001). No significant interactions, however, were observed between reducer status and treatment group. Finally, quetiapine was generally well tolerated. Statistically significant adverse events that were more common with quetiapine versus placebo include dizziness (14 vs. 4%), dry mouth (32 vs. 9%), dyspepsia (13 vs. 2%), increased appetite (11 vs. 1%), sedation (15 vs. 3%), and somnolence (34 vs. 9%).
Conclusions: This multisite clinical trial showed no efficacy for quetiapine compared with placebo at reducing alcohol consumption in heavy-drinking alcohol-dependent patients.
C1 [Litten, Raye Z.; Fertig, Joanne B.; Falk, Daniel E.; Ryan, Megan L.] NIAAA, Div Treatment & Recovery Res, Bethesda, MD 20892 USA.
[Mattson, Margaret E.] SAMHSA, Ctr Behav Hlth Stat & Qual, Rockville, MD USA.
[Collins, Joseph F.; Murtaugh, Cristin] VA Maryland Hlth Care Syst, Cooperat Studies Program Coordinating Ctr, Perry Point, MD USA.
[Ciraulo, Domenic; Afshar, Maryam] Boston Univ, Sch Med, Boston, MA 02118 USA.
[Green, Alan I.] Dartmouth Med Sch DHMC, Dept Psychiat, Lebanon, NH USA.
[Johnson, Bankole] Univ Virginia, Dept Psychiat Med, Charlottesville, VA USA.
[Pettinati, Helen; Kampman, Kyle] Univ Penn, Treatment Res Ctr, Philadelphia, PA 19104 USA.
Brown Univ, Ctr Alcohol & Addict Studies, Providence, RI 02912 USA.
[Brunette, Mary F.] Dartmouth Med Sch, Psychopharmacol Res Grp, Concord, NH USA.
[Tiouririne, Nassima A. -D.] Univ Virginia, Ctr Addict Res & Educ, Richmond, VA USA.
Decis Sci Inst PIRE, Pawtucket, RI USA.
RP Falk, DE (reprint author), NIAAA, Div Treatment & Recovery Res, 5635 Fishers Lane,Room 2040, Bethesda, MD 20892 USA.
EM falkde@mail.nih.gov
RI Leggio, Lorenzo/M-2972-2016;
OI Ciraulo, Domenic/0000-0001-7706-8765
FU National Institute on Alcohol Abuse and Alcoholism, National Institutes
of Health, Department of Health and Human Services; AstraZeneca
FX This research was supported by the National Institute on Alcohol Abuse
and Alcoholism, National Institutes of Health, Department of Health and
Human Services. The Veterans Affairs Cooperative Studies Program
(VACSP), Perry Point, MD, was the Coordinating Center; this research was
supported in part by the Investigator-Sponsored Study Program of
AstraZeneca.
NR 58
TC 34
Z9 34
U1 3
U2 9
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0145-6008
J9 ALCOHOL CLIN EXP RES
JI Alcoholism (NY)
PD MAR
PY 2012
VL 36
IS 3
BP 406
EP 416
DI 10.1111/j.1530-0277.2011.01649.x
PG 11
WC Substance Abuse
SC Substance Abuse
GA 897PC
UT WOS:000300663900004
PM 21950727
ER
PT J
AU Agrawal, A
Freedman, ND
Cheng, YC
Lin, P
Shaffer, JR
Sun, Q
Taylor, K
Yaspan, B
Cole, JW
Cornelis, MC
DeSensi, RS
Fitzpatrick, A
Heiss, G
Kang, JH
O'Connell, J
Bennett, S
Bookman, E
Bucholz, KK
Caporaso, N
Crout, R
Dick, DM
Edenberg, HJ
Goate, A
Hesselbrock, V
Kittner, S
Kramer, J
Nurnberger, JI
Qi, L
Rice, JP
Schuckit, M
van Dam, RM
Boerwinkle, E
Hu, F
Levy, S
Marazita, M
Mitchell, BD
Pasquale, LR
Bierut, LJ
AF Agrawal, Arpana
Freedman, Neal D.
Cheng, Yu-Ching
Lin, Peng
Shaffer, John R.
Sun, Qi
Taylor, Kira
Yaspan, Brian
Cole, John W.
Cornelis, Marilyn C.
DeSensi, Rebecca S.
Fitzpatrick, Annette
Heiss, Gerardo
Kang, Jae H.
O'Connell, Jeffrey
Bennett, Siiri
Bookman, Ebony
Bucholz, Kathleen K.
Caporaso, Neil
Crout, Richard
Dick, Danielle M.
Edenberg, Howard J.
Goate, Alison
Hesselbrock, Victor
Kittner, Steven
Kramer, John
Nurnberger, John I., Jr.
Qi, Lu
Rice, John P.
Schuckit, Marc
van Dam, Rob M.
Boerwinkle, Eric
Hu, Frank
Levy, Steven
Marazita, Mary
Mitchell, Braxton D.
Pasquale, Louis R.
Bierut, Laura J.
CA GENEVA Consortium
TI Measuring alcohol consumption for genomic meta-analyses of alcohol
intake: opportunities and challenges
SO AMERICAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Article
ID U-SHAPED CURVE; WIDE ASSOCIATION; GENETIC INFLUENCES;
ENVIRONMENTAL-INFLUENCES; GENOMEWIDE ASSOCIATION; DIETARY PATTERNS;
SMOKING-BEHAVIOR; CANCER RISK; DEPENDENCE; MORTALITY
AB Whereas moderate drinking may have health benefits, excessive alcohol consumption causes many important acute and chronic diseases and is the third leading contributor to preventable death in the United States. Twin studies suggest that alcohol-consumption patterns are heritable (50%); however, multiple genetic variants of modest effect size are likely to contribute to this heritable variation. Genome-wide association studies provide a tool for discovering genetic loci that contribute to variations in alcohol consumption. Opportunities exist to identify susceptibility loci with modest effect by meta-analyzing together multiple studies. However, existing studies assessed many different aspects of alcohol use, such as typical compared with heavy drinking, and these different assessments can be difficult to reconcile. In addition, many studies lack the ability to distinguish between lifetime and recent abstention or to assess the pattern of drinking during the week, and a variety of such concerns surround the appropriateness of developing a common summary measure of alcohol intake. Combining such measures of alcohol intake can cause heterogeneity and exposure misclassification, cause a reduction in power, and affect the magnitude of genetic association signals. In this review, we discuss the challenges associated with harmonizing alcohol-consumption data from studies with widely different assessment instruments, with a particular focus on large-scale genetic studies. Am J Clin Nutr 2012; 95: 539-47.
C1 [Agrawal, Arpana] Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA.
[Freedman, Neal D.; Caporaso, Neil] NCI, Bethesda, MD 20892 USA.
[Cheng, Yu-Ching; Cole, John W.; O'Connell, Jeffrey; Kittner, Steven; Mitchell, Braxton D.] Univ Maryland, Bethesda, MD USA.
[Shaffer, John R.; DeSensi, Rebecca S.; Marazita, Mary] Univ Pittsburgh, Pittsburgh, PA USA.
[Sun, Qi; Cornelis, Marilyn C.; Qi, Lu; van Dam, Rob M.; Hu, Frank] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA.
[Kang, Jae H.] Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA.
[Taylor, Kira] Univ Louisville, Louisville, KY 40292 USA.
[Heiss, Gerardo] Univ N Carolina, Chapel Hill, NC USA.
[Yaspan, Brian] Vanderbilt Univ, Nashville, TN USA.
[Fitzpatrick, Annette; Bennett, Siiri] Univ Washington, GENEVA Coordinating Ctr, Seattle, WA 98195 USA.
[Fitzpatrick, Annette; Bennett, Siiri; Bookman, Ebony] NHGRI, Morrisville, NC USA.
[Crout, Richard] W Virginia Univ, Morgantown, WV 26506 USA.
[Dick, Danielle M.] Virginia Commonwealth Univ, Richmond, VA USA.
[Edenberg, Howard J.; Nurnberger, John I., Jr.] Indiana Univ, Indianapolis, IN 46204 USA.
[Hesselbrock, Victor] Univ Connecticut, Farmington, CT USA.
[Kramer, John; Levy, Steven] Univ Iowa, Iowa City, IA USA.
[Schuckit, Marc] Univ Calif San Diego, San Diego, CA 92103 USA.
[Boerwinkle, Eric] Univ Texas Houston, Houston, TX USA.
[Pasquale, Louis R.] Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA.
RP Agrawal, A (reprint author), Washington Univ, Sch Med, Dept Psychiat, 660 S Euclid,CB 8134, St Louis, MO 63110 USA.
EM arpana@wustl.edu
RI van Dam, Rob/F-9674-2010; Lin, P/G-7702-2014; Freedman,
Neal/B-9741-2015;
OI van Dam, Rob/0000-0002-7354-8734; Freedman, Neal/0000-0003-0074-1098;
Nurnberger, John/0000-0002-7674-1767; Edenberg,
Howard/0000-0003-0344-9690; Mitchell, Braxton/0000-0003-4920-4744
FU NIH Genes, Environment and Health Initiative (GEI) [U01 HG004422]; Gene,
Environment Association Studies (GENEVA) under GEI; Johns Hopkins
University Center for Inherited Disease Research by NIH GEI
[U01HG004438]; National Institute on Alcohol Abuse and Alcoholism;
National Institute on Drug Abuse; NIH [HHSN268200782096C];
ABMRF/Foundation for Alcohol Research; Boston Obesity Nutrition Research
Center [DK46200, U01HG004399, NIH R01 HL71981, K99HL098459]; American
Heart Association Scientist Development Award; Canadian Institutes of
Health Research (MCC); National Institutes of Dental and Craniofacial
Research (NIDCR) as part of the trans-NIH GEI [U01-DE018903]; NIDCR
[R01-DE 014899, R01-DE09551, R01-DE12101]; Iowa Fluoride Study; Iowa
Bone Development Study; NIDCR through CIDR's NIH; NHLBI; National Heart,
Lung, and Blood Institute [HHSN268201100005C, HHSN268201100006C,
HHSN268201100007C, HHSN268201100008C, HHSN268201100009C,
HHSN268201100010C, HHSN268201100011C, HHSN268201100012C]; Office of
Research and Development; Medical Research Service and the Baltimore
Geriatrics Research, Education and Clinical Center of the Department of
Veterans Affairs; National Institute of Neurological Disorders and
Stroke; NIH Office of Research on Women's Health [R01 NS45012, U01
NS069208-01]; National Human Genome Research Institute [U01 HG004436];
NHGRI [U01HG004728, NEI R01EY015473]; NIH GEI [U01HG04424];
[K02DA21237]; [DA23668]; [T32 AG000262]
FX The Study of Addiction: Genetics and Environment (SAGE): supported by
the NIH Genes, Environment and Health Initiative (GEI) (U01 HG004422).
SAGE is one of the genome-wide association studies funded as part of the
Gene, Environment Association Studies (GENEVA) under GEI. Assistance
with phenotype harmonization and genotype cleaning and with the general
study coordination was provided by the GENEVA Coordinating Center (U01
HG004446). Assistance with data cleaning was provided by the National
Center for Biotechnology Information. Support for the collection of data
sets and samples was provided by the Collaborative Study on the Genetics
of Alcoholism (COGA; U10 AA008401), the Collaborative Genetic Study of
Nicotine Dependence (COGEND; P01 CA089392), and the Family Study of
Cocaine Dependence (FSCD; R01 DA013423). Funding support for genotyping,
which was performed at the Johns Hopkins University Center for Inherited
Disease Research, was provided by the NIH GEI (U01HG004438), the
National Institute on Alcohol Abuse and Alcoholism, the National
Institute on Drug Abuse, and NIH contract "High throughput genotyping
for studying the genetic contributions to human disease"
(HHSN268200782096C). LJB was supported by K02DA21237. AA receives
support from the DA23668 and ABMRF/Foundation for Alcohol Research. NHS
and HPFS: the Pilot and Feasibility program were sponsored by the Boston
Obesity Nutrition Research Center (DK46200; QS), U01HG004399 (FH), NIH
R01 HL71981 and K99HL098459 (QS), American Heart Association Scientist
Development Award (LQ), and the Canadian Institutes of Health Research
(MCC). Dental Caries: Study: "Dental Caries: Whole Genome Association
and Gene Environment Studies" 1-U01-DE018903, PI Marazita. (Included in
the alcohol cross-study were the Levy (IOWA) and Marazita (PITT) study
populations so the acknowledgements below reflect only those studies.)
Funding support for the GWAS was provided by the National Institutes of
Dental and Craniofacial Research (NIDCR) as part of the trans-NIH GEI
(U01-DE018903). Data and samples were provided by the Center for Oral
Health Research in Appalachia (a collaboration of the University of
Pittsburgh and West Virginia University funded by NIDCR R01-DE 014899)
and the Iowa Fluoride Study and the Iowa Bone Development Study, funded
by NIDCR R01-DE09551 and R01-DE12101, respectively. Genotyping was done
by the Johns Hopkins University Center for Inherited Disease Research
(CIDR), which is fully funded through a federal contract from the NIH to
The Johns Hopkins University (contract number HHSN268200782096C). Funds
for this project's genotyping were provided by the NIDCR through CIDR's
NIH contract. Assistance with phenotype harmonization and genotype
cleaning, as well as with general study coordination, was provided by
the GENEVA Coordinating Center (U01-HG004446). Atherosclerosis Risk in
Communities Study: supported by NHLBI Cardiovascular Epidemiology
Training Grant (UNC) (National Research Service Award) to KT; carried
out as a collaborative study supported by National Heart, Lung, and
Blood Institute contracts HHSN268201100005C, HHSN268201100006C,
HHSN268201100007C, HHSN268201100008C, HHSN268201100009C,
HHSN268201100010C, HHSN268201100011C, and HHSN268201100012C.; GEOS:
supported in part by the Office of Research and Development, Medical
Research Service and the Baltimore Geriatrics Research, Education, and
Clinical Center of the Department of Veterans Affairs (SK and JWC); the
National Institute of Neurological Disorders and Stroke and the NIH
Office of Research on Women's Health (R01 NS4512 and U01 NS069208-01)
(SK); the National Human Genome Research Institute (U01 HG004436) (BDM,
SK, and JO); and grant T32 AG000262 (Y-CC). GLAUGEN: supported by grants
NHGRI U01HG004728 and NEI R01EY015473 to LRP (Research to Prevent
Blindness Physician Scientist Award). Genotyping was performed at the
Broad Institute of MIT and Harvard, with funding support from the NIH
GEI (U01HG04424). The GENEVA Coordinating Center (U01HG004446) provided
assistance with genotype cleaning.
NR 74
TC 16
Z9 16
U1 2
U2 14
PU AMER SOC NUTRITION-ASN
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0002-9165
J9 AM J CLIN NUTR
JI Am. J. Clin. Nutr.
PD MAR
PY 2012
VL 95
IS 3
BP 539
EP 547
DI 10.3945/ajcn.111.015545
PG 9
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 897HK
UT WOS:000300638700003
PM 22301922
ER
PT J
AU de Souza, RJ
Bray, GA
Carey, VJ
Hall, KD
LeBoff, MS
Loria, CM
Laranjo, NM
Sacks, FM
Smith, SR
AF de Souza, Russell J.
Bray, George A.
Carey, Vincent J.
Hall, Kevin D.
LeBoff, Meryl S.
Loria, Catherine M.
Laranjo, Nancy M.
Sacks, Frank M.
Smith, Steven R.
TI Effects of 4 weight-loss diets differing in fat, protein, and
carbohydrate on fat mass, lean mass, visceral adipose tissue, and
hepatic fat: results from the POUNDS LOST trial
SO AMERICAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Article
ID RANDOMIZED CONTROLLED-TRIAL; BODY-COMPOSITION; RISK-FACTORS;
ENERGY-EXPENDITURE; OBESE WOMEN; CARDIOVASCULAR-DISEASE; LIPID
CONCENTRATIONS; COMPUTED-TOMOGRAPHY; OVERWEIGHT SUBJECTS; METABOLIC
SYNDROME
AB Background: Weight loss reduces body fat and lean mass, but whether these changes are influenced by macronutrient composition of the diet is unclear.
Objective: We determined whether energy-reduced diets that emphasize fat, protein, or carbohydrate differentially reduce total, visceral, or hepatic fat or preserve lean mass.
Design: In a subset of participants in a randomized trial of 4 weight-loss diets, body fat and lean mass (n = 424; by using dual-energy X-ray absorptiometry) and abdominal and hepatic fat (n = 165; by using computed tomography) were measured after 6 mo and 2 y. Changes from baseline were compared between assigned amounts of protein (25% compared with 15%) and fat (40% compared with 20%) and across 4 carbohydrate amounts (35% through 65%).
Results: At 6 mo, participants lost a mean (+/- SEM) of 4.2 +/- 0.3 kg (12.4%) fat and 2.1 +/- 0.3 kg (3.5%) lean mass (both P < 0.0001 compared with baseline values), with no differences between 25% and 15% protein (P > 0.10), 40% and 20% fat (P > 0.34), or 65% and 35% carbohydrate (P >= 0.27). Participants lost 2.3 +/- 0.2 kg (13.8%) abdominal fat: 1.5 +/- 0.2 kg (13.6%) subcutaneous fat and 0.9 +/- 0.1 kg (16.1%) visceral fat (all P, 0.0001 compared with baseline values), with no differences between the diets (P > 0.29). Women lost more visceral fat than did men relative to total-body fat loss. Participants regained; 40% of these losses by 2 y, with no differences between diets (P >= 0.23). Weight loss reduced hepatic fat, but there were no differences between groups (P >= 0.28). Dietary goals were not fully met; self-reported contrasts were closer to 2% protein, 8% fat, and 14% carbohydrate at 6 mo and 1%, 7%, and 10%, respectively, at 2 y.
Conclusion: Participants lost more fat than lean mass after consumption of all diets, with no differences in changes in body composition, abdominal fat, or hepatic fat between assigned macronutrient amounts. This trial was registered at clinicaltrials.gov as NCT00072995. Am J Clin Nutr 2012;95:614-25.
C1 [de Souza, Russell J.; Sacks, Frank M.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Bray, George A.; Smith, Steven R.] Pennington Biomed Res Ctr, Baton Rouge, LA USA.
[Carey, Vincent J.; Laranjo, Nancy M.; Sacks, Frank M.] Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA.
[LeBoff, Meryl S.] Brigham & Womens Hosp, Div Endocrine, Dept Med, Boston, MA 02115 USA.
Harvard Univ, Sch Med, Boston, MA USA.
[Hall, Kevin D.] NIDDK, Lab Biol Modeling, NIH, Bethesda, MD USA.
[Loria, Catherine M.] NHLBI, Bethesda, MD 20892 USA.
RP Bray, GA (reprint author), 6400 Perkins Rd, Baton Rouge, LA 70808 USA.
EM brayga@pbrc.edu
OI de Souza, Russell/0000-0001-8945-513X
FU National Heart, Lung, and Blood Institute [HL073286]; General Clinical
Research Center, NIH [RR-02635]
FX Supported by the National Heart, Lung, and Blood Institute (grant
HL073286) and the General Clinical Research Center, NIH (grant
RR-02635).
NR 62
TC 57
Z9 57
U1 2
U2 15
PU AMER SOC NUTRITION-ASN
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0002-9165
J9 AM J CLIN NUTR
JI Am. J. Clin. Nutr.
PD MAR
PY 2012
VL 95
IS 3
BP 614
EP 625
DI 10.3945/ajcn.111.026328
PG 12
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 897HK
UT WOS:000300638700013
PM 22258266
ER
PT J
AU Arpadi, SM
McMahon, DJ
Abrams, EJ
Bamji, M
Purswani, M
Engelson, ES
Horlick, M
Shane, E
AF Arpadi, Stephen M.
McMahon, Donald J.
Abrams, Elaine J.
Bamji, Mahrukh
Purswani, Murli
Engelson, Ellen S.
Horlick, Mary
Shane, Elizabeth
TI Effect of supplementation with cholecalciferol and calcium on 2-y bone
mass accrual in HIV-infected children and adolescents: a randomized
clinical trial
SO AMERICAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Article
ID VITAMIN-D DEFICIENCY; ACTIVE ANTIRETROVIRAL THERAPY; MULTIPLE HEALTH
OUTCOMES; B LIGAND RANKL; MINERAL DENSITY; PROTEASE INHIBITORS; FOREARM
FRACTURES; 25-HYDROXYVITAMIN-D LEVELS; SERUM 25-HYDROXYVITAMIN-D;
PUBERTAL CHANGES
AB Background: Skeletal abnormalities have been reported in HIV-infected children and adolescents. Although the etiology is not well understood, vitamin D deficiency may be involved.
Objective: The study objective was to evaluate the effect of vitamin D and calcium supplementation on bone mass accrual in HIV-infected youth.
Design: Perinatally HIV-infected children were randomly assigned to receive vitamin D (100,000 IU cholecalciferol given every 2 mo) and calcium (1 g/d) (supplemented group) or double placebo (placebo group) for 2 y. The total-body bone mineral content (TBBMC), total-body bone mineral density (TBBMD), spine bone mineral content (SBMC), and spine bone mineral density (SBMD) were assessed by using dual-energy X-ray absorptiometry at baseline and at 2 annual follow-up visits.
Results: Fifty-nine participants, aged 6-16 y, were randomly assigned to either the supplemented (n = 30) or the placebo (n = 29) group. At enrollment, supplemented and placebo groups did not differ with respect to age, sex, dietary intakes of vitamin D and calcium, mean baseline serum 25-hydroxyvitamin D [25(OH) D] concentration, TBBMC, TBBMD, SBMC, or SBMD. Significant increases in serum 25(OH) D were observed in the supplemented group but not in the placebo group. TBBMC, TBBMD, SBMC, and SBMD increased significantly at 1 and 2 y in both groups. No between-group differences were observed at any time before or after adjustment for stage of sexual maturation by mixed linear model analysis.
Conclusion: One gram of calcium per day and oral cholecalciferol at a dosage of 100,000 IU every 2 mo administered to HIV-infected children and adolescents did not affect bone mass accrual despite significant increases in serum 25(OH) D concentrations. This trial was registered at clinicaltrials.gov as NCT00724178. Am J Clin Nutr 2012;95:678-85.
C1 [Arpadi, Stephen M.] Columbia Univ, Coll Phys & Surg, Sergievsky Ctr, New York, NY USA.
[Arpadi, Stephen M.; Abrams, Elaine J.] Columbia Univ, Mailman Sch Publ Hlth, Dept Pediat, New York, NY USA.
[McMahon, Donald J.; Engelson, Ellen S.; Shane, Elizabeth] Columbia Univ, Mailman Sch Publ Hlth, Dept Med, New York, NY USA.
[Arpadi, Stephen M.; Abrams, Elaine J.] Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY USA.
[Abrams, Elaine J.] Columbia Univ Coll Phys & Surg, Harlem Hosp Ctr, New York, NY 10032 USA.
[Arpadi, Stephen M.; Engelson, Ellen S.] St Lukes Roosevelt Hosp, New York, NY USA.
[Bamji, Mahrukh] Metropolitan Hosp Ctr, New York, NY 10029 USA.
[Purswani, Murli] Bronx Lebanon Hosp Ctr, Bronx, NY 10456 USA.
[Horlick, Mary] NIDDK, Bethesda, MD USA.
RP Arpadi, SM (reprint author), Coll Phys & Surg, GH Sergievsky Ctr, PH Room 19-114,630 W 168th St, New York, NY 10032 USA.
EM sma2@columbia.edu
RI Ghartouchent, malek/B-9088-2012
FU NIH [DK63666, RR00645]
FX Supported by the NIH (grants DK63666 and RR00645).
NR 63
TC 17
Z9 17
U1 0
U2 3
PU AMER SOC NUTRITION-ASN
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0002-9165
J9 AM J CLIN NUTR
JI Am. J. Clin. Nutr.
PD MAR
PY 2012
VL 95
IS 3
BP 678
EP 685
DI 10.3945/ajcn.111.024786
PG 8
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 897HK
UT WOS:000300638700020
PM 22258265
ER
PT J
AU Zhang, XH
Spiegelman, D
Baglietto, L
Bernstein, L
Boggs, DA
van den Brandt, PA
Buring, JE
Gapstur, SM
Giles, GG
Giovannucci, E
Goodman, G
Hankinson, SE
Helzlsouer, KJ
Horn-Ross, PL
Inoue, M
Jung, S
Khudyakov, P
Larsson, SC
Lof, M
McCullough, ML
Miller, AB
Neuhouser, ML
Palmer, JR
Park, Y
Robien, K
Rohan, TE
Ross, JA
Schouten, LJ
Shikany, JM
Tsugane, S
Visvanathan, K
Weiderpass, E
Wolk, A
Willett, WC
Zhang, SMM
Ziegler, RG
Smith-Warner, SA
AF Zhang, Xuehong
Spiegelman, Donna
Baglietto, Laura
Bernstein, Leslie
Boggs, Deborah A.
van den Brandt, Piet A.
Buring, Julie E.
Gapstur, Susan M.
Giles, Graham G.
Giovannucci, Edward
Goodman, Gary
Hankinson, Susan E.
Helzlsouer, Kathy J.
Horn-Ross, Pamela L.
Inoue, Manami
Jung, Seungyoun
Khudyakov, Polyna
Larsson, Susanna C.
Lof, Marie
McCullough, Marjorie L.
Miller, Anthony B.
Neuhouser, Marian L.
Palmer, Julie R.
Park, Yikyung
Robien, Kim
Rohan, Thomas E.
Ross, Julie A.
Schouten, Leo J.
Shikany, James M.
Tsugane, Shoichiro
Visvanathan, Kala
Weiderpass, Elisabete
Wolk, Alicja
Willett, Walter C.
Zhang, Shumin M.
Ziegler, Regina G.
Smith-Warner, Stephanie A.
TI Carotenoid intakes and risk of breast cancer defined by estrogen
receptor and progesterone receptor status: a pooled analysis of 18
prospective cohort studies
SO AMERICAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Article
ID FOOD FREQUENCY QUESTIONNAIRE; BASE-LINE CHARACTERISTICS; BLACK WOMENS
HEALTH; VITAMIN-E; HORMONE-RECEPTOR; BETA-CAROTENE; DIETARY CAROTENOIDS;
ANTIOXIDANT INTAKE; REGRESSION-MODELS; PROPENSITY SCORES
AB Background: Epidemiologic studies examining associations between carotenoid intakes and risk of breast cancer by estrogen receptor (ER) and progesterone receptor (PR) status are limited.
Objective: We investigated these associations in a pooled analysis of 18 cohort studies.
Design: Of 1,028,438 participants followed for a maximum follow-up of 26 y across studies, 33,380 incident invasive breast cancers were identified. Study-specific RRs and 95% CIs were estimated by using Cox proportional hazards regression and then pooled by using a random-effects model.
Results: alpha-Carotene, beta-carotene, and lutein/zeaxanthin intakes were inversely associated with the risk of ER-negative (ER-) breast cancer (pooled multivariable RRs of the comparison between the highest and lowest quintiles): alpha-carotene (0.87; 95% CI: 0.78, 0.97), beta-carotene (0.84; 95% CI: 0.77, 0.93), and lutein/zeaxanthin (0.87; 95% CI: 0.79, 0.95). These variables were not inversely associated with the risk of ER-positive (ER+) breast cancer (pooled multivariable RRs for the same comparison): a-carotene (1.04; 95% CI: 0.99, 1.09), beta-carotene (1.04; 95% CI: 0.98, 1.10), and lutein/zeaxanthin (1.00; 95% CI: 0.93, 1.07). Although the pooled RRs for quintile 5 for beta-cryptoxanthin were not significant, inverse trends were observed for ER- and ER+ breast cancer (P-trend <= 0.05). Nonsignificant associations were observed for lycopene intake. The associations were largely not appreciably modified by several breast cancer risk factors. Nonsignificant associations were observed for PR-positive and PR-negative breast cancer.
Conclusions: Intakes of alpha-carotene, beta-carotene, and lutein/zeaxanthin were inversely associated with risk of ER-, but not ER+, breast cancer. However, the results need to be interpreted with caution because it is unclear whether the observed association is real or due to other constituents in the same food sources. Am J Clin Nutr 2012;95:713-25.
C1 [Zhang, Xuehong] Harvard Univ, Sch Publ Hlth, Channing Lab, Landmark Ctr,Dept Nutr, Boston, MA 02115 USA.
[Zhang, Xuehong; Spiegelman, Donna; Buring, Julie E.; Giovannucci, Edward; Hankinson, Susan E.; Willett, Walter C.; Smith-Warner, Stephanie A.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Spiegelman, Donna; Khudyakov, Polyna] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA.
[Baglietto, Laura] Canc Council Victoria, Canc Epidemiol Ctr, Carlton, Vic, Australia.
[Baglietto, Laura; Giles, Graham G.] Univ Melbourne, Ctr Mol Environm Genet & Analyt Epidemiol, Melbourne, Vic 3010, Australia.
[Bernstein, Leslie] City Hope Natl Med Ctr, Beckman Res Inst, Div Canc Etiol, Dept Populat Sci, Duarte, CA 91010 USA.
[Boggs, Deborah A.; Palmer, Julie R.] Boston Univ, Slone Epidemiol Ctr, Boston, MA 02215 USA.
[van den Brandt, Piet A.; Schouten, Leo J.] Maastricht Univ, GROW Sch Oncol & Dev Biol, Dept Epidemiol, Maastricht, Netherlands.
[Buring, Julie E.; Zhang, Shumin M.] Brigham & Womens Hosp, Dept Med, Div Prevent Med, Boston, MA 02115 USA.
[Buring, Julie E.; Giovannucci, Edward; Hankinson, Susan E.; Willett, Walter C.; Zhang, Shumin M.] Harvard Univ, Sch Med, Boston, MA USA.
[Gapstur, Susan M.; McCullough, Marjorie L.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA.
[Giovannucci, Edward; Hankinson, Susan E.; Willett, Walter C.] Brigham & Womens Hosp, Channing Lab, Dept Med, Boston, MA 02115 USA.
[Goodman, Gary; Neuhouser, Marian L.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA.
[Helzlsouer, Kathy J.] Mercy Med Ctr, Weinberg Ctr Womens Hlth & Med, Prevent & Res Ctr, Baltimore, MD USA.
[Helzlsouer, Kathy J.; Visvanathan, Kala] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Horn-Ross, Pamela L.] Canc Prevent Inst Calif, Fremont, CA USA.
[Inoue, Manami; Tsugane, Shoichiro] Natl Canc Ctr, Res Ctr Canc Prevent & Screening, Epidemiol & Prevent Div, Tokyo 104, Japan.
[Larsson, Susanna C.; Wolk, Alicja] Karolinska Inst, Natl Inst Environm Med, Div Nutr Epidemiol, Stockholm, Sweden.
[Lof, Marie] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
[Miller, Anthony B.; Rohan, Thomas E.] Univ Toronto, Dalla Lana Sch Publ Hlth, Toronto, ON, Canada.
[Park, Yikyung; Ziegler, Regina G.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Robien, Kim; Ross, Julie A.] Univ Minnesota, Masonic Canc Ctr, Minneapolis, MN USA.
[Shikany, James M.] Univ Alabama, Sch Med, Div Prevent Med, Birmingham, AL USA.
[Weiderpass, Elisabete] Univ Tromso, Inst Community Med, Tromso, Norway.
[Weiderpass, Elisabete] Canc Registry Norway, Dept Etiol Res, Oslo, Norway.
[Weiderpass, Elisabete] Folkhalsan Res Ctr, Dept Genet Epidemiol, Helsinki, Finland.
RP Zhang, XH (reprint author), Harvard Univ, Sch Publ Hlth, Channing Lab, Landmark Ctr,Dept Nutr, West Wing,401 Pk Dr, Boston, MA 02115 USA.
EM pooling@hsphsun2.harvard.edu
RI Zhang, Xuehong/E-6219-2012; Schouten, Leo/G-3713-2012; Tsugane,
Shocichiro/A-2424-2015; Larsson, Susanna/F-6065-2015; Weiderpass,
Elisabete/M-4029-2016;
OI Park, Yikyung/0000-0002-6281-489X; Larsson, Susanna/0000-0003-0118-0341;
Weiderpass, Elisabete/0000-0003-2237-0128; Palmer,
Julie/0000-0002-6534-335X; Robien, Kim/0000-0002-2120-2280; Giles,
Graham/0000-0003-4946-9099
FU NIH [CA055075]; Breast Cancer Research Foundation
FX Supported by NIH grant CA055075 and a Breast Cancer Research Foundation
grant.
NR 81
TC 35
Z9 35
U1 0
U2 8
PU AMER SOC NUTRITION-ASN
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0002-9165
J9 AM J CLIN NUTR
JI Am. J. Clin. Nutr.
PD MAR
PY 2012
VL 95
IS 3
BP 713
EP 725
DI 10.3945/ajcn.111.014415
PG 13
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 897HK
UT WOS:000300638700024
PM 22277553
ER
PT J
AU Cook, CM
Subar, AF
Troiano, RP
Schoeller, DA
AF Cook, Chad M.
Subar, Amy F.
Troiano, Richard P.
Schoeller, Dale A.
TI Relation between holiday weight gain and total energy expenditure among
40- to 69-y-old men and women (OPEN study)
SO AMERICAN JOURNAL OF CLINICAL NUTRITION
LA English
DT Article
ID DOUBLY LABELED WATER; OBESITY; EQUATION; CHILDREN; BALANCE; ADULTS; COST
AB Background: A significant proportion of the average annual body weight (BW) gain in US adults (similar to 0.5-1 kg/y) may result from modest episodes of positive energy balance during the winter holiday season.
Objective: We tested whether holiday BW gain was reduced in participants with high baseline total energy expenditure (TEE) or whether it varied by BMI (in kg/m(2)).
Design: In a secondary analysis of previously published data, Delta BW normalized over 90 d from mid-September/mid-October 1999 to mid-January/early March 2000 was analyzed by sex, age, and BMI in 443 men and women (40-69 y of age). TEE was measured by doubly labeled water. High or low energy expenditure was assessed as residual TEE after linear adjustment for age, height, and BW.
Results: No correlations between DBW and TEE or TEE residuals were found. Sixty-five percent of men and 58% of women gained >= 0.5 kg BW, with similar to 50% of both groups gaining >= 1% of preholiday BW. Obese men (BMI >= 30) gained more BW than did obese women.
Conclusions: A high preholiday absolute TEE or residual TEE did not protect against BW gain during the winter holiday quarter. It is not known whether higher than these typical TEE levels would protect against weight gain or if the observed gain may be attributed to increased food consumption and/or reduced physical activity during the holiday quarter. Am J Clin Nutr 2012;95:726-31.
C1 [Schoeller, Dale A.] Univ Wisconsin, Dept Nutr Sci, Interdept Grad Program Nutr Sci, Madison, WI 53706 USA.
[Subar, Amy F.; Troiano, Richard P.] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
RP Schoeller, DA (reprint author), Univ Wisconsin, Dept Nutr Sci, Interdept Grad Program Nutr Sci, 1415 Linden Dr, Madison, WI 53706 USA.
EM dschoell@nutrisci.wisc.edu
OI Troiano, Richard/0000-0002-6807-989X
FU National Cancer Institute, Divisions of Cancer Control and Population
Sciences and Cancer Epidemiology and Genetics
FX Supported by the National Cancer Institute, Divisions of Cancer Control
and Population Sciences and Cancer Epidemiology and Genetics.
NR 19
TC 8
Z9 8
U1 0
U2 3
PU AMER SOC NUTRITION-ASN
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0002-9165
J9 AM J CLIN NUTR
JI Am. J. Clin. Nutr.
PD MAR
PY 2012
VL 95
IS 3
BP 726
EP 731
DI 10.3945/ajcn.111.023036
PG 6
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 897HK
UT WOS:000300638700025
PM 22301936
ER
PT J
AU Cardozo, ER
Clark, AD
Banks, NK
Henne, MB
Stegmann, BJ
Segars, JH
AF Cardozo, Eden R.
Clark, Andrew D.
Banks, Nicole K.
Henne, Melinda B.
Stegmann, Barbara J.
Segars, James H.
TI The estimated annual cost of uterine leiomyomata in the United States
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Article
DE cost; fibroid tumor; uterine leiomyomata
ID HYSTERECTOMY RATES; PREGNANCY; FIBROIDS; WOMEN; COMPLICATIONS;
INFERTILITY; POPULATION; MANAGEMENT; TRIMESTER; DELIVERY
AB OBJECTIVE: The purpose of this study was to estimate the total annual societal cost of uterine fibroid tumors in the United States, based on direct and indirect costs that include associated obstetric complications.
STUDY DESIGN: A systematic review of the literature was conducted to estimate the number of women who seek treatment for symptomatic fibroid tumors annually, the costs of medical and surgical treatment, the amount of work time lost, and obstetric complications that are attributable to fibroid tumors. Total annual costs were converted to 2010 US dollars. A sensitivity analysis was performed.
RESULTS: The estimated annual direct costs (surgery, hospital admissions, outpatient visits, and medications) were $ 4.1-9.4 billion. Estimated lost work-hour costs ranged from $ 1.55-17.2 billion annually. Obstetric outcomes that were attributed to fibroid tumors resulted in a cost of $ 238 million to $ 7.76 billion annually. Uterine fibroid tumors were estimated to cost the United States $ 5.9-34.4 billion annually.
CONCLUSION: Obstetric complications that are associated with fibroid tumors contributed significantly to their economic burden. Lost work-hour costs may account for the largest proportion of societal costs because of fibroid tumors.
C1 [Cardozo, Eden R.] Northwestern Univ, Dept Obstet & Gynecol, Feinberg Sch Med, Chicago, IL 60611 USA.
[Clark, Andrew D.] Univ S Carolina, Sch Med, Greenville Hosp Syst Campus, Dept Obstet & Gynecol, Greenville, SC USA.
[Banks, Nicole K.] NHGRI, NIH, Bethesda, MD 20892 USA.
[Segars, James H.] Eunice Kennedy Shriver Natl Inst Child & Human De, Program Reprod & Adult Endocrinol, NIH, Bethesda, MD USA.
[Henne, Melinda B.] Walter Reed Army Med Ctr, Dept Obstet & Gynecol, Div Reprod Endocrinol, Washington, DC 20307 USA.
[Stegmann, Barbara J.] Univ Iowa Hosp & Clin, Dept Obstet & Gynecol, Div Reprod Endocrinol & Infertil, Iowa City, IA 52242 USA.
RP Segars, JH (reprint author), Bldg 10,CRC,Room 1E-3140,10 Ctr Dr, Bethesda, MD 20892 USA.
EM segarsj@mail.nih.gov
FU National Institute of Child Health and Human Development, National
Institutes of Health; National Institutes of Health
FX This study was supported, in part, by the Intramural Research Program of
Reproductive and Adult Endocrinology, National Institute of Child Health
and Human Development, National Institutes of Health.; We acknowledge
the support and advice of Drs Alan H. DeCherney and Vivian Pinn
(National Institutes of Health Intramural Funding; no compensation
relative to the publication). The authors appreciated the suggestions
and comments of Dr Alicia Armstrong (National Institutes of Health
Intramural Funding; no compensation relative to the publication) and the
technical expertise and assistance provided by Miriam Levy (PIRA Energy
Group; no compensation relative to this publication).
NR 39
TC 35
Z9 36
U1 0
U2 7
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9378
J9 AM J OBSTET GYNECOL
JI Am. J. Obstet. Gynecol.
PD MAR
PY 2012
VL 206
IS 3
AR 211.e1
DI 10.1016/j.ajog.2011.12.002
PG 9
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 900HW
UT WOS:000300878600021
PM 22244472
ER
PT J
AU Tita, ATN
Lai, YL
Bloom, SL
Spong, CY
Varner, MW
Ramin, SM
Caritis, SN
Grobman, WA
Sorokin, Y
Sciscione, A
Carpenter, MW
Mercer, BM
Thorp, JM
Malone, FD
Harper, M
Iams, JD
AF Tita, Alan Thevenet N.
Lai, Yinglei
Bloom, Steven L.
Spong, Catherine Y.
Varner, Michael W.
Ramin, Susan M.
Caritis, Steve N.
Grobman, William A.
Sorokin, Yoram
Sciscione, Anthony
Carpenter, Marshall W.
Mercer, Brian M.
Thorp, John M., Jr.
Malone, Fergal D.
Harper, Margaret
Iams, Jay D.
TI Timing of delivery and pregnancy outcomes among laboring nulliparous
women
SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
LA English
DT Article
DE cesarean delivery; labor; nulliparous; optimal timing of delivery;
pregnancy outcomes
ID NEONATAL RESPIRATORY MORBIDITY; REPEAT CESAREAN DELIVERY; EXPECTANT
MANAGEMENT; ELECTIVE INDUCTION; GESTATIONAL-AGE; TERM PREGNANCY;
INFANT-MORTALITY; UNITED-STATES; RISK; COMPLICATIONS
AB OBJECTIVE: The objective of the study was to compare pregnancy outcomes by completed week of gestation after 39 weeks with outcomes at 39 weeks.
STUDY DESIGN: Secondary analysis of a multicenter trial of fetal pulse oximetry in spontaneously laboring or induced nulliparous women at a gestation of 36 weeks or longer. Maternal outcomes included a composite (treated uterine atony, blood transfusion, and peripartum infections) and cesarean delivery. Neonatal outcomes included a composite of death, neonatal respiratory and other morbidities, and neonatal intensive care unit admission.
RESULTS: Among the 4086 women studied, the risks of the composite maternal outcome (P value for trend < .001), cesarean delivery (P < .001), and composite neonatal outcome (P = .047) increased with increasing gestational age from 39 to 41 or more completed weeks. Adjusted odds ratios (95% confidence interval) for 40 and 41 or more weeks, respectively, compared with 39 weeks were 1.29 (1.03-1.64) and 2.05 (1.60-2.64) for composite maternal outcome, 1.28 (1.05-1.57) and 1.75 (1.41-2.16) for cesarean delivery, and 1.25 (0.86-1.83) and 1.37 (0.90-2.09) for composite neonatal outcome.
CONCLUSION: Risks of maternal morbidity and cesarean delivery but not neonatal morbidity increased significantly beyond 39 weeks.
C1 [Tita, Alan Thevenet N.] Univ Alabama, Sch Med, Dept Obstet, Birmingham, AL 35294 USA.
[Tita, Alan Thevenet N.] Univ Alabama, Sch Med, Dept Gynecol, Birmingham, AL USA.
[Bloom, Steven L.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA.
[Ramin, Susan M.] Univ Texas Hlth Sci Ctr Houston, Houston, TX USA.
[Varner, Michael W.] Univ Utah, Sch Med, Salt Lake City, UT USA.
[Caritis, Steve N.] Univ Pittsburgh, Sch Med, Pittsburgh, PA USA.
[Grobman, William A.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA.
[Sorokin, Yoram] Wayne State Univ, Sch Med, Detroit, MI USA.
[Sciscione, Anthony] Drexel Univ, Coll Med, Philadelphia, PA 19104 USA.
[Carpenter, Marshall W.] Brown Univ, Alpert Med Sch, Providence, RI 02912 USA.
[Mercer, Brian M.] Case Western Reserve Univ, Sch Med, Cleveland, OH USA.
[Iams, Jay D.] Ohio State Univ, Coll Med, Columbus, OH 43210 USA.
[Thorp, John M., Jr.] Univ N Carolina, Sch Med, Chapel Hill, NC USA.
[Harper, Margaret] Wake Forest Univ Hlth Sci, Winston Salem, NC USA.
[Malone, Fergal D.] Columbia Univ, Coll Phys & Surg, New York, NY USA.
[Lai, Yinglei] George Washington Univ, Ctr Biostat, Washington, DC USA.
[Spong, Catherine Y.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD USA.
RP Tita, ATN (reprint author), Univ Alabama, Sch Med, Dept Obstet, Birmingham, AL 35294 USA.
RI Malone, Fergal/D-6233-2012; Varner, Michael/K-9890-2013
OI caritis, steve/0000-0002-2169-0712; Varner, Michael/0000-0001-9455-3973
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development [HD21410, HD27860, HD27869, HD27915, HD27917, HD34116,
HD34136, HD34208, HD40485, HD40500, HD40512, HD40544, HD40545, HD40560,
HD36801]
FX The project described was supported by grants from the Eunice Kennedy
Shriver National Institute of Child Health and Human Development
(HD21410, HD27860, HD27869, HD27915, HD27917, HD34116, HD34136, HD34208,
HD40485, HD40500, HD40512, HD40544, HD40545, HD40560, and HD36801).
NR 37
TC 0
Z9 0
U1 0
U2 3
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9378
J9 AM J OBSTET GYNECOL
JI Am. J. Obstet. Gynecol.
PD MAR
PY 2012
VL 206
IS 3
AR 239.e1
DI 10.1016/j.ajog.2011.12.006
PG 8
WC Obstetrics & Gynecology
SC Obstetrics & Gynecology
GA 900HW
UT WOS:000300878600033
PM 22244471
ER
PT J
AU Yi, L
Liu, Q
Orandle, MS
Sadiq-Ali, S
Koontz, SM
Choi, U
Torres-Velez, FJ
Jackson, SH
AF Yi, Liang
Liu, Qi
Orandle, Marlene S.
Sadiq-Ali, Sara
Koontz, Sherry M.
Choi, Uimook
Torres-Velez, Fernando J.
Jackson, Sharon H.
TI p47(Phox) Directs Murine Macrophage Cell Fate Decisions
SO AMERICAN JOURNAL OF PATHOLOGY
LA English
DT Article
ID CHRONIC GRANULOMATOUS-DISEASE; LISTERIA-MONOCYTOGENES INFECTION;
PHAGOCYTE NADPH OXIDASE; ALTERNATIVE ACTIVATION; DENDRITIC CELLS; MODEL;
MICE; EXPRESSION; RESPONSES; SYSTEM
AB Macrophage differentiation and function are pivotal for cell survival from infection and involve the processing of microenvironmental signals that determine macrophage cell fate decisions to establish appropriate inflammatory balance. NADPH oxidase 2 (Nox2)-deficient chronic granulomatous disease (CGD) mice that lack the gp91(Phox) (gp91P(hox-/-)) catalytic subunit show high mortality rates compared with wild-type mice when challenged by infection with Listeria monocylogenes (Lm), whereas p47(phox)-deficient (p47(phox-/-)) CGD mice show survival rates that are similar to those of wild-type mice. We demonstrate that such survival results from a skewed macrophage differentiation program in p47(phox-/-) mice that favors the production of higher levels of alternatively activated macrophages (AAMacs) compared with levels of either wild-type or gp91(phox-/-) mice. Furthermore, the adoptive transfer of AAMacs from p47(phox-/-) mice can rescue gp91(phox-/-) mice during primary Lm infection. Key features of the protective function provided by p47(phox-/-) AAMacs against Lin infection are enhanced production of IL-1 alpha and killing of Lm. Molecular analysis of this process indicates that p47(phox-/-) macrophages are hyperresponsive to EL-4 and show higher Stat6 phosphorylation levels and signaling coupled to downstream activation of AAMac transcripts in response to IL-4 stimulation. Notably, restoring p47(phox) protein expression levels reverts the p47(phox)-dependent AAMac phenotype. Our results indicate that p47(phox) is a previously unrecognized regulator for IL-4 signaling pathways that are important for macrophage cell fate choice. (Am J Pathol 2012, 180: 1049-1058; DOI: 10.1016/j.ajpath.2011.11.019)
C1 [Choi, Uimook; Jackson, Sharon H.] NIAID, Genet Immunotherapy Sect, Host Def Lab, NIH, Bethesda, MD 20892 USA.
[Yi, Liang; Liu, Qi; Sadiq-Ali, Sara; Koontz, Sherry M.; Jackson, Sharon H.] NIAID, Mol Trafficking Unit, NIH, Bethesda, MD 20892 USA.
[Orandle, Marlene S.] NIAID, Infect Dis Pathogenesis Sect, Comparat Med Branch, NIH, Bethesda, MD 20892 USA.
[Torres-Velez, Fernando J.] USDA, Foreign Anim Dis Diagnost Lab, Phum Isl Anim Dis Ctr, Greenport, NY USA.
RP Jackson, SH (reprint author), NIAID, Genet Immunotherapy Sect, Host Def Lab, NIH, CRC Bldg 5 W Labs,Room 5-3942,10 Ctr Dr MSC 1456, Bethesda, MD 20892 USA.
EM sjackson@niaid.nih.gov
FU National Institute of Allergy and Infectious Diseases; NIH; National
Institute on Minority Health and Health Disparities, NIH
FX Supported by the Intramural Research Program of the National Institute
of Allergy and Infectious Diseases, NIH and in part by the National
Institute on Minority Health and Health Disparities, NIH.
NR 30
TC 9
Z9 9
U1 0
U2 1
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9440
J9 AM J PATHOL
JI Am. J. Pathol.
PD MAR
PY 2012
VL 180
IS 3
BP 1049
EP 1058
DI 10.1016/j.ajpath.2011.11.019
PG 10
WC Pathology
SC Pathology
GA 902EU
UT WOS:000301022200018
PM 22222227
ER
PT J
AU Miller, EK
Hernandez, JZ
Wimmenauer, V
Shepherd, BE
Hijano, D
Libster, R
Serra, ME
Bhat, N
Batalle, JP
Mohamed, Y
Reynaldi, A
Rodriguezs, A
Otello, M
Pisapia, N
Bugna, J
Bellabarba, M
Kraft, D
Coviello, S
Ferolla, FM
Chen, A
London, SJ
Siberry, GK
Williams, JV
Polack, FP
AF Miller, E. Kathryn
Zea Hernandez, Johanna
Wimmenauer, Vera
Shepherd, Bryan E.
Hijano, Diego
Libster, Romina
Elina Serra, M.
Bhat, Niranjan
Batalle, Juan P.
Mohamed, Yassir
Reynaldi, Andrea
Rodriguezs, Andrea
Otello, Monica
Pisapia, Nestor
Bugna, Jimena
Bellabarba, Miguel
Kraft, David
Coviello, Silvina
Martin Ferolla, F.
Chen, Aaron
London, Stephanie J.
Siberry, George K.
Williams, John V.
Polack, Fernando P.
TI A Mechanistic Role for Type III IFN-lambda(1) in Asthma Exacerbations
Mediated by Human Rhinoviruses
SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
LA English
DT Article
DE asthma; interferon-lambda; rhinovirus; children; asthma exacerbation
ID VIRUS-INDUCED ASTHMA; INTERFERON-LAMBDA; NEUTROPHIL RECRUITMENT;
RESPIRATORY-TRACT; ALLERGIC-ASTHMA; INDUCED SPUTUM; MESSENGER-RNA;
CHILDREN; CELLS; AIRWAY
AB Rationale: Human rhinoviruses (HRV) are the leading cause of upper respiratory infections and have been postulated to trigger asthma exacerbations. However, whether HRV are detected during crises because upper respiratory infections often accompany asthma attacks, or because they specifically elicit exacerbations, is unclear. Moreover, although several hypotheses have been advanced to explain virus-induced exacerbations, their mechanism remains unclear.
Objectives: To determine the role of H RV in pediatric asthma exacerbations and the mechanisms mediating wheezing.
Methods: We prospectively studied 409 children with asthma presenting with upper respiratory infection in the presence or absence of wheezing. Candidate viral and immune mediators of illness were compared among children with asthma with different degrees of severity of acute asthma.
Measurements and Main Results: HRV infections specifically associated with asthma exacerbations, even after adjusting for relevant demographic and clinical variables defined a priori (odds ratio, 1.90; 95% confidence interval, 1.21-2.99; P = 0.005). No difference in virus titers, HRV species, and inflammatory or allergic molecules was observed between wheezing and nonwheezing children infected with HRV. Type III IFN-lambda(1) levels were higher in wheezing children infected with HRV compared with nonwheezing (P < 0.001) and increased with worsening symptoms (P < 0.001). Moreover, after adjusting for IFN-lambda(1), children with asthma infected with HRV were no longer more likely to wheeze than those who were HRV-negative (odds ratio, 1.18; 95% confidence interval, 0.57-2.46; P = 0.66).
Conclusions: Our findings suggest that HRV infections in children with asthma are specifically associated with acute wheezing, and that type III IFN-lambda(1)., responses mediate exacerbations caused by HRV. Modulation of IFN-lambda(1) should be studied as a therapeutic target for exacerbations caused by HRV.
C1 [Polack, Fernando P.] Vanderbilt Univ, Vanderbilt Vaccine Ctr, Dept Pediat, Nashville, TN 37232 USA.
[Zea Hernandez, Johanna; Wimmenauer, Vera; Hijano, Diego; Libster, Romina; Elina Serra, M.; Batalle, Juan P.; Bugna, Jimena; Coviello, Silvina; Martin Ferolla, F.; Polack, Fernando P.] Fdn INFANT, Buenos Aires, DF, Argentina.
[Bhat, Niranjan] Johns Hopkins Univ, Dept Pediat, Baltimore, MD 21218 USA.
[Reynaldi, Andrea; Bellabarba, Miguel] Hosp Mi Pueblo, Buenos Aires, DF, Argentina.
[Rodriguezs, Andrea] Hosp Evita Pueblo, Buenos Aires, DF, Argentina.
[Otello, Monica] Hosp Iriarte, Buenos Aires, DF, Argentina.
[Pisapia, Nestor] Hosp V Lopez & Planes, Buenos Aires, DF, Argentina.
[Chen, Aaron] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
[London, Stephanie J.] NIEHS, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA.
[Siberry, George K.] Eunice Kennedy Shriver NICHD, NIH, Bethesda, MD USA.
RP Polack, FP (reprint author), Vanderbilt Univ, Vanderbilt Vaccine Ctr, Dept Pediat, 221 Kirkland Hall, Nashville, TN 37232 USA.
EM fernando.p.polack@vanderbilt.edu
RI Williams, John/F-6962-2010;
OI Williams, John/0000-0001-8377-5175; London,
Stephanie/0000-0003-4911-5290
FU Thrasher Research Fund; [KL2 RR24977-03]; [1K23AI091691-01]
FX Supported by the Thrasher Research Fund (to F.P.P.) and KL2 RR24977-03
and 1K23AI091691-01 (to E.K.M.).
NR 48
TC 44
Z9 45
U1 0
U2 3
PU AMER THORACIC SOC
PI NEW YORK
PA 61 BROADWAY, FL 4, NEW YORK, NY 10006 USA
SN 1073-449X
J9 AM J RESP CRIT CARE
JI Am. J. Respir. Crit. Care Med.
PD MAR 1
PY 2012
VL 185
IS 5
BP 508
EP 516
DI 10.1164/rccm.201108-1462OC
PG 9
WC Critical Care Medicine; Respiratory System
SC General & Internal Medicine; Respiratory System
GA 900AG
UT WOS:000300858400011
PM 22135341
ER
PT J
AU Miettinen, M
Wang, ZF
AF Miettinen, Markku
Wang, Zeng-Feng
TI Prox1 Transcription Factor as a Marker for Vascular Tumors-Evaluation of
314 Vascular Endothelial and 1086 Nonvascular Tumors
SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY
LA English
DT Article
DE hemangioma; hemangioendothelioma; lymphangioma; angiosarcoma; Prox1;
podoplanin; CD34
ID GROWTH-FACTOR RECEPTOR-3; D2-40 IMMUNOHISTOCHEMISTRY;
LYMPHATIC-ENDOTHELIUM; KAPOSIS-SARCOMA; CELLS; BLOOD; PHENOTYPE;
HEMANGIOENDOTHELIOMA; DIFFERENTIATION; ANGIOSARCOMAS
AB Prox 1, a transcription factor important in the regulation and maintenance of the lymphatic endothelial phenotype, is consistently expressed in lymphangiomas and Kaposi sarcoma and has also been reported in Kaposiform hemangioendothelioma. However, information on its distribution in vascular tumors, such as angiosarcoma, is limited. In this study, we examined selected normal tissues and 314 vascular endothelial and 1086 nonvascular tumors to get an insight into the biology of these tumors and on potential diagnostic use of Prox 1 as an immunohistochemical marker. In adult tissues, Prox 1 was essentially restricted to lymphatic endothelia, with expression in subsets of pancreatic and gastrointestinal epithelia. However, it was also detected in embryonic liver and heart. Prox 1 was consistently expressed in lymphangiomas, venous hemangiomas, Kaposi sarcoma, in endothelia of spindle cell hemangioma, Kaposiform hemangioendothelioma, and retiform hemangioendothelioma, and in half of epithelioid hemangioendotheliomas. It was present in most cutaneous angiosarcomas from different sites but was less commonly expressed in deep soft tissue and visceral angiosarcomas. In contrast, Prox 1 was generally absent in capillary and cavernous hemangiomas. In positive hemangiomas and angiosarcomas it was coexpressed with podoplanin, another marker of the lymphatic endothelial phenotype. There was an inverse correlation with CD34 expression. The expression in mesenchymal nonendothelial neoplasm was limited. Prox 1 was detected in 5 of 27 synovial sarcomas, specifically in the epithelia of biphasic tumors. Four of 16 Ewing sarcomas and 5 of 15 paragangliomas were also positive. All melanomas and undifferentiated sarcomas were negative. Among epithelial neoplasms, Prox 1 was detected in 18 of 38 colonic carcinomas and 10 of 15 cholangiocarcinomas and in a minority of pulmonary, prostatic, and endometrial adenocarcinomas. The common Prox 1 expression in angiosarcoma and its rare presence in nonvascular mesenchymal tumors make this marker suitable for the diagnosis of angiosarcoma and Kaposi sarcoma. However, the presence of Prox 1 in some malignant epithelial tumors necessitates caution in applying Prox 1 as a marker for vascular tumors. Common Prox 1 expression in angiosarcoma may reflect the lymphatic endothelial phenotype in these tumors. Its patterns of expression in hemangiomas and angiosarcoma may be diagnostically useful and offer a new parameter in the biological classification of vascular tumors.
C1 [Miettinen, Markku; Wang, Zeng-Feng] NCI, Pathol Lab, Bethesda, MD 20892 USA.
RP Miettinen, M (reprint author), NCI, Pathol Lab, 9000 Rockville Pike,Bldg 10,Rm 2B50, Bethesda, MD 20892 USA.
EM miettinenmm@mail.nih.gov
FU NCI
FX This work was supported as a part of NCI's Intramural Research Program.
The authors have disclosed that they have no significant relationships
with, or financial interest in, any commercial companies pertaining to
this article.
NR 31
TC 26
Z9 27
U1 1
U2 5
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0147-5185
J9 AM J SURG PATHOL
JI Am. J. Surg. Pathol.
PD MAR
PY 2012
VL 36
IS 3
BP 351
EP 359
PG 9
WC Pathology; Surgery
SC Pathology; Surgery
GA 902KY
UT WOS:000301038200004
PM 22067331
ER
PT J
AU Peprah, E
AF Peprah, Emmanuel
TI Fragile X Syndrome: The FMR1 CGG Repeat Distribution Among World
Populations
SO ANNALS OF HUMAN GENETICS
LA English
DT Review
DE FMR1 gene; fragile X mutation; prevalence
ID MENTALLY-RETARDED CHILDREN; PREMATURE OVARIAN FAILURE;
SINGLE-NUCLEOTIDE-POLYMORPHISM; TREMOR/ATAXIA SYNDROME FXTAS;
MESSENGER-RNA; PREMUTATION CARRIERS; FOUNDER CHROMOSOMES; GENETIC
DIVERSITY; DXS548/FRAXAC1 HAPLOTYPES; INTELLECTUAL DISABILITY
AB Fragile X syndrome (FXS) is characterized by moderate to severe intellectual disability, which is accompanied by macroorchidism and distinct facial morphology. FXS is caused by the expansion of the CGG trinucleotide repeat in the 5' untranslated region of the fragile X mental retardation 1 (FMR1) gene. The syndrome has been studied in ethnically diverse populations around the world and has been extensively characterized in several populations. Similar to other trinucleotide expansion disorders, the gene-specific instability of FMR1 is not accompanied by genomic instability. Currently we do not have a comprehensive understanding of the molecular underpinnings of gene-specific instability associated with tandem repeats. Molecular evidence from in vitro experiments and animal models supports several pathways for gene-specific trinucleotide repeat expansion. However, whether the mechanisms reported from other systems contribute to trinucleotide repeat expansion in humans is not clear. To understand how repeat instability in humans could occur, the CGG repeat expansion is explored through molecular analysis and population studies which characterized CGG repeat alleles of FMR1. Finally, the review discusses the relevance of these studies in understanding the mechanism of trinucleotide repeat expansion in FXS.
C1 [Peprah, Emmanuel] NHGRI, Ctr Res Genom & Global Hlth, NIH, Bethesda, MD 20892 USA.
[Peprah, Emmanuel] Emory Univ, Sch Med, Dept Human Genet, Atlanta, GA 30322 USA.
RP Peprah, E (reprint author), NHGRI, Ctr Res Genom & Global Hlth, NIH, Bldg 12A,RM 4047,12 South Dr,MSC 5635, Bethesda, MD 20892 USA.
EM peprahek@mail.nih.gov
FU Emory University
FX This project was supported by the Emory University Fellowships in
Research and Science Teaching (FIRST) Program. Additional support from
the Intramural Research Program of the NIH, National Human Genome
Research Institute, Center on Genomics and Global Health is
acknowledged. I would also like to acknowledge the kind editorial
assistance of the NIH Fellows Editorial Board.
NR 165
TC 24
Z9 26
U1 1
U2 16
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0003-4800
J9 ANN HUM GENET
JI Ann. Hum. Genet.
PD MAR
PY 2012
VL 76
BP 178
EP 191
DI 10.1111/j.1469-1809.2011.00694.x
PN 2
PG 14
WC Genetics & Heredity
SC Genetics & Heredity
GA 894SM
UT WOS:000300447100008
PM 22188182
ER
PT J
AU Sionov, E
Chang, YC
Garraffo, HM
Dolan, MA
Ghannoum, MA
Kwon-Chung, KJ
AF Sionov, Edward
Chang, Yun C.
Garraffo, H. Martin
Dolan, Michael A.
Ghannoum, Mahmoud A.
Kwon-Chung, Kyung J.
TI Identification of a Cryptococcus neoformans Cytochrome P450 Lanosterol
14 alpha-Demethylase (Erg11) Residue Critical for Differential
Susceptibility between Fluconazole/Voriconazole and
Itraconazole/Posaconazole
SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
LA English
DT Article
ID FLUCONAZOLE RESISTANCE; AMINO-ACID; REDUCED SUSCEPTIBILITY;
ASPERGILLUS-FUMIGATUS; MAINTENANCE THERAPY; INFECTED PATIENTS; AIDS;
MENINGITIS; ITRACONAZOLE; HETERORESISTANCE
AB Cryptococcus neoformans strains resistant to azoles due to mutations causing alterations in the ERG11 gene, encoding lanosterol 14 alpha-demethylase, have rarely been reported. In this study, we have characterized a C. neoformans serotype A strain that is resistant to high concentrations of fluconazole (FLC). This strain, which was isolated from an FLC-treated patient, contained five missense mutations in the ERG11 gene compared to the sequence of reference strain H99. Molecular manipulations of the ERG11 gene coupled with susceptibility to triazole revealed that a single missense mutation resulting in the replacement of tyrosine by phenylalanine at amino acid 145 was sufficient to cause the high FLC resistance of the strain. Importantly, this newly identified point mutation in the ERG11 gene of C. neoformans afforded resistance to voriconazole (VRC) but increased susceptibility to itraconazole (ITC) and posaconazole (PSC), which are structurally similar to each other but distinct from FLC/VRC. The in vitro susceptibility/resistance of the strains with or without the missense mutation was reflected in the therapeutic efficacy of FLC versus ITC in the animals infected with the strains. This study shows the importance of the Y145F alteration of Erg11 in C. neoformans for manifestation of differential susceptibility toward different triazoles. It underscores the necessity of in vitro susceptibility testing for each FLC-resistant C. neoformans clinical isolate against different groups of azoles in order to assist patient management.
C1 [Sionov, Edward; Chang, Yun C.; Kwon-Chung, Kyung J.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
[Dolan, Michael A.] NIAID, Bioinformat & Computat Biosci Branch, Off Cyber Infrastruct & Computat Biol, NIH, Bethesda, MD 20892 USA.
[Garraffo, H. Martin] NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
[Ghannoum, Mahmoud A.] Case Western Reserve Univ, Ctr Med Mycol, Cleveland, OH 44106 USA.
RP Kwon-Chung, KJ (reprint author), NIAID, Lab Clin Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM June_Kwon-Chung@nih.gov
FU National Institute of Allergy and Infectious Diseases, NIH
FX This study was supported by funds from the intramural program of the
National Institute of Allergy and Infectious Diseases, NIH.
NR 30
TC 27
Z9 28
U1 0
U2 2
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0066-4804
J9 ANTIMICROB AGENTS CH
JI Antimicrob. Agents Chemother.
PD MAR
PY 2012
VL 56
IS 3
BP 1162
EP 1169
DI 10.1128/AAC.05502-11
PG 8
WC Microbiology; Pharmacology & Pharmacy
SC Microbiology; Pharmacology & Pharmacy
GA 897DN
UT WOS:000300623300003
PM 22155829
ER
PT J
AU Sohl, CD
Singh, K
Kasiviswanathan, R
Copeland, WC
Mitsuya, H
Sarafianos, SG
Anderson, KS
AF Sohl, Christal D.
Singh, Kamlendra
Kasiviswanathan, Rajesh
Copeland, William C.
Mitsuya, Hiroaki
Sarafianos, Stefan G.
Anderson, Karen S.
TI Mechanism of Interaction of Human Mitochondrial DNA Polymerase gamma
with the Novel Nucleoside Reverse Transcriptase Inhibitor 4
'-Ethynyl-2-Fluoro-2 '-Deoxyadenosine Indicates a Low Potential for Host
Toxicity
SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
LA English
DT Article
ID IMMUNODEFICIENCY-VIRUS TYPE-1; ANTIRETROVIRAL-THERAPY; LIPODYSTROPHY;
RECOGNITION; VARIANTS; SUBUNIT; ANALOGS; DRUGS
AB The potent antiretroviral 4'-ethynyl-2-fluoro-2'-deoxyadenosine (EFdA) is a promising experimental agent for treating HIV infection. Pre-steady-state kinetics were used to characterize the interaction of EFdA-triphosphate (EFdA-TP) with human mitochondrial DNA polymerase gamma (Pol gamma) to assess the potential for toxicity. Pol gamma incorporated EFdA-TP 4,300-fold less efficiently than dATP, with an excision rate similar to ddATP. This strongly indicates EFdA is a poor Pol gamma substrate, suggesting minimal Pol gamma-mediated toxicity, although this should be examined under clinical settings.
C1 [Sohl, Christal D.; Anderson, Karen S.] Yale Univ, Sch Med, Dept Pharmacol, New Haven, CT 06510 USA.
[Singh, Kamlendra; Sarafianos, Stefan G.] Univ Missouri, Sch Med, Dept Mol Microbiol & Immunol, Columbia, MO 65212 USA.
[Kasiviswanathan, Rajesh; Copeland, William C.] Natl Inst Environm Hlth Sci, Mol Genet Lab, NIH, DHHS, Res Triangle Pk, NC USA.
[Mitsuya, Hiroaki] Kumamoto Univ, Grad Sch Med Sci, Dept Infect Dis, Kumamoto, Japan.
[Mitsuya, Hiroaki] Kumamoto Univ, Grad Sch Med Sci, Dept Hematol, Kumamoto, Japan.
[Mitsuya, Hiroaki] NCI, Expt Retrovirol Sect, HIV & AIDS Malignancy Branch, NIH, Bethesda, MD 20892 USA.
RP Anderson, KS (reprint author), Yale Univ, Sch Med, Dept Pharmacol, New Haven, CT 06510 USA.
EM karen.anderson@yale.edu
RI Kasiviswanathan, Rajesh/D-2744-2012
FU NIH [R01 GM049551, F32 GM099289, AI094715, AI076119, AI079801,
AI074389]; NIH, NIEHS [ES 065080]
FX This work was supported by NIH grants R01 GM049551 (to K.S.A.), F32
GM099289 (to C.D.S.), AI094715, AI076119, AI079801, and AI074389 (to
S.G.S.) and by the Intramural Research Program of the NIH, NIEHS, ES
065080 (to W.C.C.).
NR 29
TC 11
Z9 11
U1 0
U2 4
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0066-4804
J9 ANTIMICROB AGENTS CH
JI Antimicrob. Agents Chemother.
PD MAR
PY 2012
VL 56
IS 3
BP 1630
EP 1634
DI 10.1128/AAC.05729-11
PG 5
WC Microbiology; Pharmacology & Pharmacy
SC Microbiology; Pharmacology & Pharmacy
GA 897DN
UT WOS:000300623300070
PM 22155823
ER
PT J
AU Lang, TF
Sigurdsson, S
Karlsdottir, G
Oskarsdottir, D
Sigmarsdottir, A
Chengshi, J
Kornak, J
Harris, TB
Sigurdsson, G
Jonsson, BY
Siggeirsdottir, K
Eiriksdottir, G
Gudnason, V
Keyak, JH
AF Lang, T. F.
Sigurdsson, S.
Karlsdottir, G.
Oskarsdottir, D.
Sigmarsdottir, A.
Chengshi, J.
Kornak, J.
Harris, T. B.
Sigurdsson, G.
Jonsson, B. Y.
Siggeirsdottir, K.
Eiriksdottir, G.
Gudnason, V.
Keyak, J. H.
TI Age-related loss of proximal femoral strength in elderly men and women:
The Age Gene/Environment Susceptibility Study - Reykjavik
SO BONE
LA English
DT Article
DE Hip fracture; Osteoporosis; Bone strength; Finite element modeling;
Computed tomography; Proximal femur
ID HIP FRACTURE RISK; FINITE-ELEMENT MODELS; BONE LOSS;
COMPUTED-TOMOGRAPHY; OLDER MEN; PREDICTION; FEMUR; GEOMETRY; DENSITY;
WEIGHT
AB The risk of hip fracture rises rapidly with age, and is particularly high in women. This increase in fracture risk reflects both the age-related change in the risk of falling and decrements in the strength of the proximal femur. To better understand the extent to which proximal femoral density, structure and strength change with age as a function of gender, we have carried out a longitudinal analysis of proximal femoral volumetric quantitative computed tomographic (vQCT) images in men and women, analyzing changes in trabecular and cortical bone properties, and using subject-specific finite element modeling (FEM) to estimate changes in bone strength. In the AGES-Reykjavik Study vQCT scans of the hip were performed at a baseline visit in 2002-2006 and at a second visit 5.05 +/- 0.25 years later. From these, 223 subjects (111 men, 112 women, aged 68-87 years) were randomly selected. The subjects were evaluated for longitudinal changes in three bone variables assessed in a region similar to the total femur region quantified by DXA: areal bone mineral density (aBMD), trabecular volumetric bone mineral density (tBMD) and the ratio of cortical to total tissue volume (cvol/ivol). They were also evaluated for changes in bone strength using FEM models of the left proximal femur. Models were analyzed under single-limb stance loading (F-Stance), which approximates normal physiologic loading of the hip, as well as a load approximating a fall onto the posterolateral aspect of the greater trochanter (F-Fall). We computed five-year absolute and percentage changes in aBmD, tBMD, cvol/ivol, F-Fall and F-Stance. The Mann-Whitney Test was employed to compare changes in bone variables between genders and the Wilcoxon Signed Rank Test was used to compare changes in bone strength between loading conditions. Multiple (linear) regression was employed to determine the association of changes in F-Fall and F-Stance with baseline age and five-year weight loss. Both men and women showed declines in indices of proximal femoral density and structure (aBMD: men -3.9 +/- 6.0%, women -6.1 +/- 6.2%; tBMD: men -14.8 +/- 20.3%, women -23.9 +/- 26.8%; cvol/ivol: men -2.6 +/- 4.6%, women -4.7 +/- 4.8%, gender difference: p<0.001). Both men and women lost bone strength in each loading condition (F-Stance: men -4.2 +/- 9.9%, women -8.3 +/- 8.5%; F-Fall: men -7.0 +/- 15.7%, women -12.8 +/- 13.2%; all changes from baseline p<0.0001). The gender difference in bone strength loss was statistically significant in both loading conditions (p<0.001 for F-Stance and P<0.01 for F-Fall) and F-Fall, was lost at a higher rate than F-Stance in men (p<0.01) and women (p<0.0001). The gender difference in strength loss was statistically significant after adjustment for baseline age and weight loss in both loading conditions (p<0.01). In these multi-linear models, men showed increasing rates of bone loss with increasing age (F-Fall: p=0.002; F-Stance; p=0.03), and women showed increasing bone strength loss with higher degrees of weight loss (F-Stance: p=0.003). The higher loss of F-Fall compared to F-Stance supports previous findings in animal and human studies that the sub-volumes of bone stressed under normal physiologic loading are relatively better protected in aging.
The gender difference in hip bone strength loss is consistent with the higher incidence of hip fractureamong elderly women. (C) 2011 Elsevier Inc. All rights reserved.
C1 [Lang, T. F.] Univ Calif San Francisco, Dept Radiol & Biomed Imaging, San Francisco, CA 94143 USA.
[Sigurdsson, S.; Karlsdottir, G.; Oskarsdottir, D.; Sigmarsdottir, A.; Sigurdsson, G.; Siggeirsdottir, K.; Eiriksdottir, G.; Gudnason, V.] Iceland Heart Assoc Res Inst, Kopavogur, Iceland.
[Chengshi, J.; 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.] Malmo Univ Hosp, Malmo, Sweden.
[Oskarsdottir, D.; Sigurdsson, G.] Univ Iceland, Reykjavik, Iceland.
[Keyak, J. H.] Univ Calif Irvine, Dept Radiol Sci, Irvine, CA 92717 USA.
[Keyak, J. H.] Univ Calif Irvine, Dept Biomed Engn, Irvine, CA USA.
[Keyak, J. H.] Univ Calif Irvine, Dept Mech & Aerosp Engn, Irvine, CA 92717 USA.
RP Lang, TF (reprint author), Univ Calif San Francisco, Dept Radiol & Biomed Imaging, 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; Lang,
Thomas/0000-0002-3720-8038
FU NIH/NIA [R01-AG028832]; NIH [N01-AG-12100]; NIA; Hjartavernd (the
Icelandic Heart Association); Althingi (the Icelandic Parliament)
FX This study was supported by NIH/NIA R01-AG028832. 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 21
Z9 21
U1 0
U2 6
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 8756-3282
J9 BONE
JI Bone
PD MAR
PY 2012
VL 50
IS 3
BP 743
EP 748
DI 10.1016/j.bone.2011.12.001
PG 6
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 897KR
UT WOS:000300650100021
PM 22178403
ER
PT J
AU Davis, MS
Kovacic, BL
Marini, JC
Shih, AJ
Kozloff, KM
AF Davis, Mathieu S.
Kovacic, Bethany L.
Marini, Joan C.
Shih, Albert J.
Kozloff, Kenneth M.
TI Increased susceptibility to microdamage in Brtl/+ mouse model for
osteogenesis imperfecta
SO BONE
LA English
DT Article
DE Microdamage; Osteogenesis imperfecta; Mouse model; Fracture toughness;
Collagen
ID SUPPRESSED BONE TURNOVER; I COLLAGEN; BIOMECHANICAL PROPERTIES;
DECREASED BONE; RAT ULNA; FATIGUE; TOUGHNESS; ACCUMULATION; FRACTURE;
BISPHOSPHONATES
AB Osteogenesis imperfecta (OI) is a genetic disease of collagen or collagen-related proteins that adversely impacts bone mass and fracture resistance. Little is known regarding the role that microdamage plays in OI and whether or not OI bone is more prone to damage accumulation than bone with unaffected collagen. The Brtl/+ mouse is a heterozygous model for OI which contains a Gly349Cys substitution in one COL1A1 allele, and demonstrates a low ductility phenotype. At 8 weeks of age. Brtl/+ demonstrates an increase in osteoclast number, which mimics the upregulated bone turnover often found in OI patients. We hypothesize that upregulated osteoclast activity in Brtl/+ is due, in part, to increased remodeling associated with microdamage repair. In the present study, we used Brtl/+ to investigate the susceptibility of OI bone to microdamage. The mouse ulnar loading model was used to induce microdamage and to test the hypothesis that Brtl/+ is more susceptible to damage accumulation than age-matched wild type (WT) counterparts. Linear elastic fracture mechanics (LEFM) was used to investigate the fracture toughness properties of both Brtl/+ and WT bones to determine if there is any correlation with toughness and the degree of microdamage.
Results show that Brtl/+ ulnae subject to normal cage activity demonstrate an inherently larger amount of microdamage than WT controls. Following axial compressive loading, Brtl/+ ulnae are more prone to damage than WT counterparts despite demonstrating a greater resistance to whole-bone deformation. Fracture toughness results demonstrate that Brtl/+ specimens, despite not exhibiting a significant difference, display a trend toward lower fracture toughness values than their WT counterparts. Correlations show that microdamage levels tend to increase as fracture toughness decreases. Together, these findings may have strong clinical implications for explaining increased fragility and remodeling activity in OI patients. (C) 2011 Elsevier Inc. All rights reserved.
C1 [Davis, Mathieu S.; Shih, Albert J.] Univ Michigan, Dept Mech Engn, Ann Arbor, MI 48109 USA.
[Kovacic, Bethany L.; Shih, Albert J.; Kozloff, Kenneth M.] Univ Michigan, Dept Biomed Engn, Ann Arbor, MI 48109 USA.
[Kozloff, Kenneth M.] Univ Michigan, Dept Orthopaed Surg, Ann Arbor, MI 48109 USA.
[Marini, Joan C.] NICHHD, BEMB, NIH, Bethesda, MD 20892 USA.
RP Kozloff, KM (reprint author), 2015 Biomed Sci Res Bldg,109 Zina Pitcher Pl, Ann Arbor, MI 48109 USA.
EM kenkoz@umich.edu
FU American Society for Bone and Mineral Research
FX Research was supported in part by the American Society for Bone and
Mineral Research.
NR 47
TC 10
Z9 10
U1 1
U2 5
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 8756-3282
J9 BONE
JI Bone
PD MAR
PY 2012
VL 50
IS 3
BP 784
EP 791
DI 10.1016/j.bone.2011.12.007
PG 8
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 897KR
UT WOS:000300650100027
PM 22207275
ER
PT J
AU Agurs-Collins, T
Rohrmann, S
Sutcliffe, C
Bienstock, JL
Monsegue, D
Akereyeni, F
Bradwin, G
Rifai, N
Pollak, MN
Platz, EA
AF Agurs-Collins, Tanya
Rohrmann, Sabine
Sutcliffe, Catherine
Bienstock, Jessica L.
Monsegue, Deborah
Akereyeni, Folasade
Bradwin, Gary
Rifai, Nader
Pollak, Michael N.
Platz, Elizabeth A.
TI Racial variation in umbilical cord blood sex steroid hormones and the
insulin-like growth factor axis in African-American and white female
neonates
SO CANCER CAUSES & CONTROL
LA English
DT Article
DE Umbilical cord blood; IGF axis; Sex steroid hormones; African-American
ID BREAST-CANCER RISK; FACTOR BINDING-PROTEINS; I IGF-I; BIRTH-WEIGHT;
UNITED-STATES; POSTMENOPAUSAL WOMEN; INTRAUTERINE GROWTH; TESTOSTERONE
LEVELS; HEAD CIRCUMFERENCE; TERM NEWBORNS
AB To evaluate whether there is racial variation in venous umbilical cord blood concentrations of sex steroid hormones and the insulin-like growth factor (IGF) axis between female African-American and white neonates.
Maternal and birth characteristics and venous umbilical cord blood samples were collected from 77 African-American and 41 white full-term uncomplicated births at two urban hospitals in 2004 and 2005. Cord blood was measured for testosterone, dehydroespiandrosterone-sulfate, estradiol, and sex steroid hormone-binding globulin (SHBG) by immunoassay. IGF-1, IGF-2, and IGF-binding protein-3 (IGFBP-3) were measured by ELISA. Crude and multivariable-adjusted geometric mean concentrations were computed for the hormones.
African-American neonates weighed less at birth (3,228 g vs. 3,424 g, p < 0.004) than whites. Birth weight was positively correlated with IGF-1, IGFBP-3, and the molar ratio of IGF-1 to IGFBP-3, but inversely correlated with the molar ratio of IGF-2 to IGFBP-3. Adjusted models showed higher testosterone (1.82 ng/ml vs. 1.47 ng/ml, p = 0.006) and the molar ratio of testosterone to SHBG (0.42 vs. 0.30, p = 0.03) in African-American compared to white female neonates. IGF-1, IGF-2, and IGFBP-3 were lower in African-American compared to white female neonates, but only the difference for IGF-2 remained significant (496.5 ng/ml vs. 539.2 ng/ml, p = 0.04).
We provide evidence of racial variation in cord blood testosterone and testosterone to SHBG in African-American compared to white female neonates, and higher IGF-2 in white compared to African-American female neonates. Findings suggest plausible explanations for a prenatal influence on subsequent breast cancer risk and mortality. Further work is needed to confirm these observations.
C1 [Agurs-Collins, Tanya] NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
[Rohrmann, Sabine] Univ Zurich, Inst Social & Prevent Med, Dept Canc Epidemiol & Prevent, CH-8006 Zurich, Switzerland.
[Sutcliffe, Catherine; Platz, Elizabeth A.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Bienstock, Jessica L.] Johns Hopkins Univ, Sch Med, Dept Gynecol & Obstet, Baltimore, MD 21205 USA.
[Monsegue, Deborah] Howard Univ, Ctr Canc, Washington, DC 20059 USA.
[Akereyeni, Folasade] Howard Univ, Howard Univ Human Genome Ctr, Washington, DC 20059 USA.
[Bradwin, Gary; Rifai, Nader] Harvard Univ, Sch Med, Dept Lab Med, Boston, MA USA.
[Bradwin, Gary; Rifai, Nader] Childrens Hosp, Boston, MA 02115 USA.
[Pollak, Michael N.] McGill Univ, Jewish Gen Hosp, Dept Med & Oncol, Montreal, PQ H3T 1E2, Canada.
[Platz, Elizabeth A.] Johns Hopkins Med Inst, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21205 USA.
[Platz, Elizabeth A.] Johns Hopkins Med Inst, James Buchanan Brady Urol Inst, Baltimore, MD 21205 USA.
RP Agurs-Collins, T (reprint author), NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA.
EM collinsta@mail.nih.gov
RI Pollak, Michael/G-9094-2011; Rohrmann, Sabine/D-2113-2012
OI Pollak, Michael/0000-0003-3047-0604;
FU National Cancer Institute [CA091431, CA091409]
FX We thank Anna DeNooyer, MHS, research assistant, and Stacey Meyerer,
laboratory manager, both at the Johns Hopkins Bloomberg School of Public
Health, for their assistance in the conduct of this study, the delivery
room nurses at the Prince George's Hospital Center and the Johns Hopkins
Hospital for collecting the cord blood specimens, and Yuzhen Tao in the
laboratory of Dr. Pollak for overseeing the laboratory assays. Authors
received grant support from National Cancer Institute grant U54 (Howard
CA091431) and U54 (Hopkins CA091409).
NR 52
TC 4
Z9 4
U1 0
U2 0
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0957-5243
EI 1573-7225
J9 CANCER CAUSE CONTROL
JI Cancer Causes Control
PD MAR
PY 2012
VL 23
IS 3
BP 445
EP 454
DI 10.1007/s10552-011-9893-6
PG 10
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 900ML
UT WOS:000300891100005
PM 22252677
ER
PT J
AU Kitahara, CM
Platz, EA
Freeman, LEB
Black, A
Hsing, AW
Linet, MS
Park, Y
Schairer, C
de Gonzalez, AB
AF Kitahara, Cari M.
Platz, Elizabeth A.
Freeman, Laura E. Beane
Black, Amanda
Hsing, Ann W.
Linet, Martha S.
Park, Yikyung
Schairer, Catherine
de Gonzalez, Amy Berrington
TI Physical activity, diabetes, and thyroid cancer risk: a pooled analysis
of five prospective studies
SO CANCER CAUSES & CONTROL
LA English
DT Article
DE Physical activity; Energy expenditure; Type 2 diabetes; Insulin
resistance; Thyroid neoplasms; Prospective study
ID BODY-MASS INDEX; ANTHROPOMETRIC FACTORS; UNITED-STATES; COHORT; OBESITY;
MEN; WEIGHT; ADULTS; CARCINOGENESIS; METAANALYSIS
AB Although many studies have linked obesity with increased risk of thyroid cancer, few have investigated the role of obesity-related lifestyle characteristics and medical conditions in the etiology of this disease. We examined the associations of self-reported physical activity and diabetes history with thyroid cancer risk in a large pooled analysis of prospective cohort studies.
Data from five prospective studies in the U.S. (n = 362,342 men, 312,149 women) were coded using standardized exposure, covariate, and outcome definitions. Hazard ratios (HR) and 95% confidence intervals (CI) for thyroid cancer were estimated using age as the time metric and adjusting for sex, education, race, marital status, cigarette smoking, body mass index, alcohol intake, and cohort. Effect modification by other risk factors (e.g., age, sex, and body mass index) and differences by cancer subtype (e.g., papillary, follicular) were also examined.
Over follow-up (median = 10.5 years), 308 men and 510 women were diagnosed with a first primary thyroid cancer. Overall, subjects reporting the greatest amount of physical activity had an increased risk of the disease (HR = 1.18, 95% CI:1.00-1.39); however, this association was restricted to participants who were overweight/obese (a parts per thousand yen25 kg/m(2); HR = 1.34, 95% CI:1.09-1.64) as opposed to normal-weight (< 25 kg/m(2); HR = 0.92, 95% CI:0.69-1.22; P-interaction = 0.03). We found no overall association between self-reported history of diabetes and thyroid cancer risk (HR = 1.08, 95% CI:0.83-1.40).
Neither physical inactivity nor diabetes history was associated with increased risk of thyroid cancer. While it may have been a chance finding, the possible increased risk associated with greater physical activity warrants further investigation.
C1 [Kitahara, Cari M.; Freeman, Laura E. Beane; Black, Amanda; Hsing, Ann W.; Linet, Martha S.; Park, Yikyung; Schairer, Catherine; de Gonzalez, Amy Berrington] NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20852 USA.
[Platz, Elizabeth A.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
RP Kitahara, CM (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, EPS 7056,6120 Execut Blvd, Rockville, MD 20852 USA.
EM kitaharac@mail.nih.gov
RI Kitahara, Cari/R-8267-2016;
OI Park, Yikyung/0000-0002-6281-489X
FU National Cancer Institute, National Institutes of Health; Florida
Department of Health (FDOH)
FX This work was supported in part by the Intramural Research Program of
the National Cancer Institute, National Institutes of Health. Specific
to NIH-AARP: Cancer incidence data from the Atlanta metropolitan area
were collected by the Georgia Center for Cancer Statistics, Department
of Epidemiology, Rollins School of Public Health, Emory University.
Cancer incidence data from California were collected by the California
Department of Health Services, Cancer Surveillance Section. Cancer
incidence data from the Detroit metropolitan area were collected by the
Michigan Cancer Surveillance Program, Community Health Administration,
State of Michigan. The Florida cancer incidence data used in this report
were collected by the Florida Cancer Data System (FCDC) under contract
with the Florida Department of Health (FDOH). The views expressed herein
are solely those of the authors and do not necessarily reflect those of
the FCDC or FDOH. Cancer incidence data from Louisiana were collected by
the Louisiana Tumor Registry, Louisiana State University Medical Center
in New Orleans. Cancer incidence data from New Jersey were collected by
the New Jersey State Cancer Registry, Cancer Epidemiology Services, New
Jersey State Department of Health and Senior Services. Cancer incidence
data from North Carolina were collected by the North Carolina Central
Cancer Registry. Cancer incidence data from Pennsylvania were supplied
by the Division of Health Statistics and Research, Pennsylvania
Department of Health, Harrisburg, Pennsylvania. The Pennsylvania
Department of Health specifically disclaims responsibility for any
analyses, interpretations or conclusions. Cancer incidence data from
Arizona were collected by the Arizona Cancer Registry, Division of
Public Health Services, Arizona Department of Health Services. Cancer
incidence data from Texas were collected by the Texas Cancer Registry,
Cancer Epidemiology and Surveillance Branch, Texas Department of State
Health Services. We are indebted to the participants in the NIH-AARP
Diet and Health Study for their outstanding cooperation. We also thank
Sigurd Hermansen and Kerry Grace Morrissey from Westat for study
outcomes ascertainment and management and Leslie Carroll at Information
Management Services for data support and analysis. In memory of Dr.
Arthur Schatzkin, visionary investigator who founded the NIH-AARP Diet
and Health Study.
NR 28
TC 18
Z9 19
U1 0
U2 7
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0957-5243
J9 CANCER CAUSE CONTROL
JI Cancer Causes Control
PD MAR
PY 2012
VL 23
IS 3
BP 463
EP 471
DI 10.1007/s10552-012-9896-y
PG 9
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 900ML
UT WOS:000300891100007
PM 22294499
ER
PT J
AU Brinton, LA
Schwartz, L
Spitz, MR
Park, Y
Hollenbeck, AR
Gierach, GL
AF Brinton, Louise A.
Schwartz, Lauren
Spitz, Margaret R.
Park, Yikyung
Hollenbeck, Albert R.
Gierach, Gretchen L.
TI Unopposed estrogen and estrogen plus progestin menopausal hormone
therapy and lung cancer risk in the NIH-AARP Diet and Health Study
Cohort
SO CANCER CAUSES & CONTROL
LA English
DT Article
DE Lung cancer; Menopausal hormone therapy; Risk; Histology
ID REPLACEMENT THERAPY; REPRODUCTIVE FACTORS; POSTMENOPAUSAL WOMEN;
RECEPTOR EXPRESSION; NURSES HEALTH; SMOKING; ASSOCIATION;
ADENOCARCINOMA; PREGNANCY
AB Previous studies have reported that lung cancer risk may be decreased, increased, or unaffected by prior use of menopausal hormone therapy (MHT).
To assess this issue further, we examined relationships among 118,008 women, ages 50-71 years who were recruited during 1995-1996 for the NIH-AARP Diet and Health Study and in whom 2,097 incident lung carcinomas were identified during follow-up through 2006. Multivariable Cox proportional hazards models estimated relative risks (RR) and 95% confidence intervals (CIs) associated with various measures of self-reported MHT use.
We found no evidence that either estrogen therapy (ET)-only or estrogen plus progestin therapy (EPT) use was substantially related to subsequent lung cancer risk (respective RRs and 95% CIs for ever use = 0.97, 0.86-1.09 and 1.03, 0.90-1.17). There were no significant variations according to currency or duration of use of either formulation, nor was there evidence that risks varied within subgroups defined by cigarette smoking or body size. The absence of effect was seen for nearly all lung cancer subtypes, with the exception of an increased risk of undifferentiated/large cell cancers associated with long-term ET-only use (p (trend) = 0.02), a relationship not observed among EPT users.
Our results failed to support any substantial alterations in lung cancer risk associated with use of either unopposed estrogen or estrogen plus progestin MHT, even when detailed exposure measures and other risk predictors were considered.
C1 [Brinton, Louise A.; Schwartz, Lauren; Park, Yikyung; Gierach, Gretchen L.] NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20852 USA.
[Spitz, Margaret R.] Baylor Coll Med, Dan L Duncan Canc Ctr, Houston, TX 77030 USA.
[Hollenbeck, Albert R.] AARP, Org & Tracking Res Dept, Washington, DC 20049 USA.
RP Brinton, LA (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd,Room 5018,Suite 550, Rockville, MD 20852 USA.
EM brinton@nih.gov
RI Brinton, Louise/G-7486-2015; Gierach, Gretchen/E-1817-2016;
OI Brinton, Louise/0000-0003-3853-8562; Gierach,
Gretchen/0000-0002-0165-5522; Park, Yikyung/0000-0002-6281-489X
FU NIH
FX This investigation was supported by the Intramural Research Program of
the NIH.
NR 40
TC 4
Z9 4
U1 0
U2 0
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 0957-5243
J9 CANCER CAUSE CONTROL
JI Cancer Causes Control
PD MAR
PY 2012
VL 23
IS 3
BP 487
EP 496
DI 10.1007/s10552-012-9904-2
PG 10
WC Oncology; Public, Environmental & Occupational Health
SC Oncology; Public, Environmental & Occupational Health
GA 900ML
UT WOS:000300891100009
PM 22367699
ER
PT J
AU Weir, SJ
DeGennaro, LJ
Austin, CP
AF Weir, Scott J.
DeGennaro, Louis J.
Austin, Christopher P.
TI Repurposing Approved and Abandoned Drugs for the Treatment and
Prevention of Cancer through Public-Private Partnership
SO CANCER RESEARCH
LA English
DT Article
C1 [Weir, Scott J.] Univ Kansas Canc Ctr, Inst Advancing Med Innovat, Kansas City, KS USA.
[DeGennaro, Louis J.] Leukemia & Lymphoma Soc, White Plains, NY USA.
[Austin, Christopher P.] NIH Ctr Translat Therapeut, Rockville, MD USA.
RP Weir, SJ (reprint author), Kansas Masonic Canc Res, 3901 Rainbow Blvd,Mailstop 1027, Kansas City, KS 66160 USA.
EM sweir@kumc.edu
FU Intramural NIH HHS [ZIB HG200319-08]
NR 6
TC 29
Z9 29
U1 0
U2 8
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD MAR 1
PY 2012
VL 72
IS 5
BP 1055
EP 1058
DI 10.1158/0008-5472.CAN-11-3439
PG 4
WC Oncology
SC Oncology
GA 901TG
UT WOS:000300989100004
PM 22246671
ER
PT J
AU White, KL
Schildkraut, JM
Palmieri, RT
Iversen, ES
Berchuck, A
Vierkant, RA
Rider, DN
Charbonneau, B
Cicek, MS
Sutphen, R
Birrer, MJ
Pharoah, PPD
Song, H
Tyrer, J
Gayther, SA
Ramus, SJ
Wentzensen, N
Yang, HP
Garcia-Closas, M
Phelan, CM
Cunningham, JM
Fridley, BL
Sellers, TA
Goode, EL
AF White, Kristin L.
Schildkraut, Joellen M.
Palmieri, Rachel T.
Iversen, Edwin S., Jr.
Berchuck, Andrew
Vierkant, Robert A.
Rider, David N.
Charbonneau, Bridget
Cicek, Mine S.
Sutphen, Rebecca
Birrer, Michael J.
Pharoah, Paul P. D.
Song, Honglin
Tyrer, Jonathan
Gayther, Simon A.
Ramus, Susan J.
Wentzensen, Nicolas
Yang, Hannah P.
Garcia-Closas, Montserrat
Phelan, Catherine M.
Cunningham, Julie M.
Fridley, Brooke L.
Sellers, Thomas A.
Goode, Ellen L.
CA Ovarian Canc Assoc Consortium
TI Ovarian Cancer Risk Associated with Inherited Inflammation-Related
Variants
SO CANCER RESEARCH
LA English
DT Article
ID BREAST-CANCER; POLYMORPHISMS; GENES; SUSCEPTIBILITY; SNPS
AB The importance of inflammation pathways to the development of many human cancers prompted us to examine the associations between single-nucleotide polymorphisms (SNP) in inflammation-related genes and risk of ovarian cancer. In a multisite case-control study, we genotyped SNPs in a large panel of inflammatory genes in 930 epithelial ovarian cancer cases and 1,037 controls using a custom array and analyzed by logistic regression. SNPs with P < 0.10 were evaluated among 3,143 cases and 2,102 controls from the Follow-up of Ovarian Cancer Genetic Association and Interaction Studies (FOCI) post-GWAS collaboration. Combined analysis revealed association with SNPs rs17561 and rs4848300 in the interleukin gene IL1A which varied by histologic subtype (P-heterogeneity = 0.03). For example, IL1A rs17561, which correlates with numerous inflammatory phenotypes, was associated with decreased risk of clear cell, mucinous, and endometrioid subtype, but not with the most common serous subtype. Genotype at rs1864414 in the arachidonate 5-lipoxygenase ALOX5 was also associated with decreased risk. Thus, inherited variation in IL1A and ALOX5 seems to affect ovarian cancer risk which, for IL1A, is limited to rarer subtypes. Given the importance of inflammation in tumorigenesis and growing evidence of subtype-specific features in ovarian cancer, functional investigations will be important to help clarify the importance of inherited variation related to inflammation in ovarian carcinogenesis. Cancer Res; 72(5); 1064-9. (C) 2012 AACR.
C1 [Goode, Ellen L.] Mayo Clin & Mayo Fdn, Dept Hlth Sci Res, Rochester, MN 55905 USA.
[White, Kristin L.] Columbia Univ, New York, NY 10027 USA.
[Schildkraut, Joellen M.; Berchuck, Andrew] Duke Univ, Duke Comprehens Canc Ctr, Durham, NC 27706 USA.
[Palmieri, Rachel T.] Univ N Carolina, Gillings Sch Global Publ Hlth, Chapel Hill, NC 27515 USA.
[Iversen, Edwin S., Jr.] Duke Univ, Dept Stat Sci, Durham, NC 27706 USA.
[Sutphen, Rebecca] Univ S Florida, Coll Med, Tampa, FL 33620 USA.
[Birrer, Michael J.] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Pharoah, Paul P. D.; Song, Honglin; Tyrer, Jonathan] Univ Cambridge, Cambridge CB2 1TN, England.
[Gayther, Simon A.; Ramus, Susan J.] Univ So Calif, Los Angeles, CA 90089 USA.
[Wentzensen, Nicolas; Yang, Hannah P.] NCI, Bethesda, MD 20892 USA.
[Garcia-Closas, Montserrat] Inst Canc Res, Sutton, Surrey, England.
[Phelan, Catherine M.; Sellers, Thomas A.] Univ S Florida, Coll Med, H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL 33612 USA.
RP Goode, EL (reprint author), Mayo Clin & Mayo Fdn, Dept Hlth Sci Res, 200 1st St SW, Rochester, MN 55905 USA.
EM egoode@mayo.edu
RI Fridley, Brooke/D-8315-2015; Garcia-Closas, Montserrat /F-3871-2015;
OI Fridley, Brooke/0000-0001-7739-7956; Garcia-Closas, Montserrat
/0000-0003-1033-2650; Vierkant, Robert/0000-0001-6242-5221; Ramus,
Susan/0000-0003-0005-7798
FU National Cancer Institute U19 Post-GWAS Initiative [U19-CA148112]; Mayo
Clinic Ovarian Cancer SPORE [P50-CA136393]; National Cancer Institute
[R01-CA086888, R01-CA122443, R01-CA106414, R01-CA76016, R01-CA114343];
Cancer Research UK [A10119, A10124, A8339, A6187, A11306, A7058];
Medical Research Council [G0801875-89310]; Ovarian Cancer Research Fund;
Mayo Foundation
FX The scientific development and funding for this project were in part
supported by the National Cancer Institute U19 Post-GWAS Initiative
(U19-CA148112), the Mayo Clinic Ovarian Cancer SPORE (P50-CA136393),
National Cancer Institute Research Project Grants (R01-CA086888,
R01-CA122443, R01-CA106414, R01-CA76016, R01-CA114343), Cancer Research
UK (A10119, A10124, A8339, A6187, A11306, A7058), the Medical Research
Council (G0801875-89310), the Ovarian Cancer Research Fund, and the Mayo
Foundation.
NR 20
TC 23
Z9 24
U1 0
U2 6
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
EI 1538-7445
J9 CANCER RES
JI Cancer Res.
PD MAR 1
PY 2012
VL 72
IS 5
BP 1064
EP 1069
DI 10.1158/0008-5472.CAN-11-3512
PG 6
WC Oncology
SC Oncology
GA 901TG
UT WOS:000300989100006
PM 22282663
ER
PT J
AU Gasperini, P
Espigol-Frigole, G
McCormick, PJ
Salvucci, O
Maric, D
Uldrick, TS
Polizzotto, MN
Yarchoan, R
Tosato, G
AF Gasperini, Paola
Espigol-Frigole, Georgina
McCormick, Peter J.
Salvucci, Ombretta
Maric, Dragan
Uldrick, Thomas S.
Polizzotto, Mark N.
Yarchoan, Robert
Tosato, Giovanna
TI Kaposi Sarcoma Herpesvirus Promotes Endothelial-to-Mesenchymal
Transition through Notch-Dependent Signaling
SO CANCER RESEARCH
LA English
DT Article
ID GENE-EXPRESSION; E-CADHERIN; DNA-SEQUENCES; CANCER-CELLS; PROTEIN;
TRANSFORMATION; ACTIVATION; INFECTION; BETA; DIFFERENTIATION
AB Endothelial-to-mesenchymal transition (EndMT) is now widely considered a pivotal contributor to cancer progression. In this study, we show that the Kaposi's sarcoma (KS)-associated herpesvirus (KSHV) is a sufficient cause of EndMT, potentially helping to explain the aggressiveness of KS that occurs commonly in AIDS patients. Upon KSHV infection, primary dermal microvascular endothelial cells lost expression of endothelial markers and acquired expression of mesenchymal markers, displaying new invasive and migratory properties along with increased survival. KSHV activated Notch-induced transcription factors Slug and ZEB1, and canonical Notch signaling was required for KSHV-induced EndMT. In contrast, KSHV did not utilize the TGF beta signaling pathway, which has also been linked to EndMT. Within KS lesions, KSHV-infected spindle cells displayed features compatible with KSHV-induced EndMT including a complex phenotype of endothelial and mesenchymal properties, Notch activity, and nuclear ZEB1 expression. Our results show that KSHV engages the EndMT program to increase the invasiveness and survival of infected endothelial cells, traits that likely contribute to viral persistence and malignant progression. One important implication of our findings is that therapeutic approaches to disrupt the Notch pathway may offer novel approaches for KS treatment. Cancer Res; 72(5); 1157-69. (C) 2012 AACR.
C1 [Uldrick, Thomas S.; Polizzotto, Mark N.; Yarchoan, Robert] NINDS, NIH, NCI,CCR, Cellular Oncol Lab,HIV & AIDS Malignancy Branch, Bethesda, MD 20892 USA.
[Maric, Dragan] NINDS, Neurophysiol Lab, Bethesda, MD 20892 USA.
RP Espigol-Frigole, G (reprint author), NINDS, NIH, NCI,CCR, Cellular Oncol Lab,HIV & AIDS Malignancy Branch, Bldg 37,Room 4134, Bethesda, MD 20892 USA.
EM Georgina.Frigole@mail.nih.gov
RI McCormick, Peter/E-7387-2012
OI McCormick, Peter/0000-0002-2225-5181
FU CCR/NCI/NIH; NINDS/NIH
FX The work was supported by Intramural research program of CCR/NCI/NIH and
NINDS/NIH.
NR 50
TC 27
Z9 27
U1 0
U2 8
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD MAR 1
PY 2012
VL 72
IS 5
BP 1157
EP 1169
DI 10.1158/0008-5472.CAN-11-3067
PG 13
WC Oncology
SC Oncology
GA 901TG
UT WOS:000300989100015
PM 22237624
ER
PT J
AU Weinstein, SJ
Stolzenberg-Solomon, RZ
Kopp, W
Rager, H
Virtamo, J
Albanes, D
AF Weinstein, Stephanie J.
Stolzenberg-Solomon, Rachael Z.
Kopp, William
Rager, Helen
Virtamo, Jarmo
Albanes, Demetrius
TI Impact of Circulating Vitamin D Binding Protein Levels on the
Association between 25-Hydroxyvitamin D and Pancreatic Cancer Risk: A
Nested Case-Control Study
SO CANCER RESEARCH
LA English
DT Article
ID PROSTATE-CANCER; GC-GLOBULIN; PLASMA 1,25-DIHYDROXYVITAMIN-D; SCREENING
TRIAL; D METABOLITES; SERUM; LUNG; COHORT
AB High concentrations of circulating 25-hydroxyvitamin D [25(OH)D] have been associated with elevated pancreatic cancer risk. As this is contrary to an expected inverse association between vitamin D status and cancer, we examined whether vitamin D binding protein (DBP), the primary carrier of vitamin D compounds in circulation, plays a role in this relationship. Prediagnostic serum DBP and 25(OH)D were studied in relation to risk of pancreatic cancer in a nested case-control study of 234 cases and 234 controls in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study of Finnish men. ORs and 95% CIs were estimated using logistic regression, and statistical tests were two-sided. We found that DBP and 25(OH)D were correlated (r = 0.27, P < 0.0001), and DBP was inversely associated with pancreatic cancer risk (OR = 0.66, 95% CI = 0.39-1.12, for the highest vs. lowest quartile; P-trend = 0.02). Importantly, this association seemed to have a threshold between quartiles 2 to 4 and quartile 1, and was primarily evident among men with concurrent high 25(OH)D concentrations (OR = 0.33, 95% CI = 0.16-0.70 for highest vs. lowest quartile; P-trend = 0.002), with no association in men with lower serum 25(OH) D (OR 1.28, 95% CI = 0.62-2.61 for highest vs. lowest quartile, P-trend 0.63, P-interaction = 0.01). Men with higher 25(OH) D concentrations and serum DBP below the median showed greatly elevated risk of pancreatic cancer (OR = 5.01, 95% CI 2.33-10.78, for highest vs. lowest quartile; P-trend < 0.0001), while risk was weakly inversely associated with serum 25(OH) D when DBP concentrations were higher (P-interaction = 0.001). Taken together, our findings indicate that higher DBP concentrations may sequester more 25(OH) D and reduce free 25(OH) D bioavailability. Simultaneous examination of DBP and 25(OH) D may be important in determining the association of vitamin D with cancer risk. Cancer Res; 72(5); 1190-8. (C) 2012 AACR.
C1 [Weinstein, Stephanie J.; Stolzenberg-Solomon, Rachael Z.; Albanes, Demetrius] NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20982 USA.
[Kopp, William; Rager, Helen] SAIC Frederick Inc, NCI Frederick, Clin Support Lab, Frederick, MD USA.
[Virtamo, Jarmo] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland.
RP Albanes, D (reprint author), NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Executive Blvd,Suite 320, Bethesda, MD 20982 USA.
EM daa@nih.gov
RI Albanes, Demetrius/B-9749-2015
FU National Cancer Institute (NCI) at the NIH; U.S. Public Health Service,
NCI, NIH [N01-CN-45165, N01-RC-45035, N01-RC-37004, HHSN261201000006C,
HHSN261200800001E]
FX This work was supported by the Intramural Research Program of the
National Cancer Institute (NCI) at the NIH. In addition, this research
was supported by U.S. Public Health Service contracts (N01-CN-45165,
N01-RC-45035, N01-RC-37004, HHSN261201000006C, and HHSN261200800001E)
from the NCI, NIH.
NR 35
TC 37
Z9 38
U1 0
U2 12
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 0008-5472
J9 CANCER RES
JI Cancer Res.
PD MAR 1
PY 2012
VL 72
IS 5
BP 1190
EP 1198
DI 10.1158/0008-5472.CAN-11-2950
PG 9
WC Oncology
SC Oncology
GA 901TG
UT WOS:000300989100018
PM 22232734
ER
PT J
AU Rosenberger, A
Bickeboller, H
McCormack, V
Brenner, DR
Duell, EJ
Tjonneland, A
Friis, S
Muscat, JE
Yang, P
Wichmann, HE
Heinrich, J
Szeszenia-Dabrowska, N
Lissowska, J
Zaridze, D
Rudnai, P
Fabianova, E
Janout, V
Bencko, V
Brennan, P
Mates, D
Schwartz, AG
Cote, ML
Zhang, ZF
Morgenstern, H
Oh, SS
Field, JK
Raji, O
McLaughlin, JR
Wiencke, J
LeMarchand, L
Neri, M
Bonassi, S
Andrew, AS
Lan, Q
Hu, W
Orlow, I
Park, BJ
Boffetta, P
Hung, RJ
AF Rosenberger, Albert
Bickeboeller, Heike
McCormack, Valerie
Brenner, Darren R.
Duell, Eric J.
Tjonneland, Anne
Friis, Soren
Muscat, Joshua E.
Yang, Ping
Wichmann, H-Erich
Heinrich, Joachim
Szeszenia-Dabrowska, Neonila
Lissowska, Jolanta
Zaridze, David
Rudnai, Peter
Fabianova, Eleonora
Janout, Vladimir
Bencko, Vladimir
Brennan, Paul
Mates, Dana
Schwartz, Ann G.
Cote, Michele L.
Zhang, Zuo-Feng
Morgenstern, Hal
Oh, Sam S.
Field, John K.
Raji, Olaide
McLaughlin, John R.
Wiencke, John
LeMarchand, Loic
Neri, Monica
Bonassi, Stefano
Andrew, Angeline S.
Lan, Qing
Hu, Wei
Orlow, Irene
Park, Bernard J.
Boffetta, Paolo
Hung, Rayjean J.
TI Asthma and lung cancer risk: a systematic investigation by the
International Lung Cancer Consortium
SO CARCINOGENESIS
LA English
DT Article
ID OBSTRUCTIVE PULMONARY-DISEASE; NONMALIGNANT RESPIRATORY CONDITIONS;
UNITED-STATES; NEVER-SMOKERS; NONSMOKING WOMEN; FAMILY-HISTORY;
PROSPECTIVE COHORT; RESIDENTIAL RADON; DISTINCT DISEASES;
META-REGRESSION
AB Asthma has been hypothesized to be associated with lung cancer (LC) risk. We conducted a pooled analysis of 16 studies in the International Lung Cancer Consortium (ILCCO) to quantitatively assess this association and compared the results with 36 previously published studies. In total, information from 585 444 individuals was used. Study-specific measures were combined using random effects models. A meta-regression and subgroup meta-analyses were performed to identify sources of heterogeneity. The overall LC relative risk (RR) associated with asthma was 1.28 [95% confidence intervals (CIs) = 1.16-1.41] but with large heterogeneity (I-2 = 73%, P < 0.001) between studies. Among ILCCO studies, an increased risk was found for squamous cell (RR = 1.69, 95%, CI = 1.26-2.26) and for small-cell carcinoma (RR = 1.71, 95% CI = 0.99-2.95) but was weaker for adenocarcinoma (RR = 1.09, 95% CI = 0.88-1.36). The increased LC risk was strongest in the 2 years after asthma diagnosis (RR = 2.13, 95% CI = 1.09-4.17) but subjects diagnosed with asthma over 10 years prior had no or little increased LC risk (RR = 1.10, 95% CI = 0.94-1.30). Because the increased incidence of LC was chiefly observed in small cell and squamous cell lung carcinomas, primarily within 2 years of asthma diagnosis and because the association was weak among never smokers, we conclude that the association may not reflect a causal effect of asthma on the risk of LC.
C1 [Rosenberger, Albert; Bickeboeller, Heike] Univ Gottingen, Univ Med Ctr, Dept Genet Epidemiol, D-37073 Gottingen, Germany.
[McCormack, Valerie; McLaughlin, John R.] Int Agcy Res Canc, Sect Environm & Radiat, F-69372 Lyon, France.
[Brenner, Darren R.; McLaughlin, John R.; Hung, Rayjean J.] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada.
[Brenner, Darren R.; Hung, Rayjean J.] Univ Toronto, Dalla Lana Sch Publ Hlth, Toronto, ON M5S 1A1, Canada.
[Duell, Eric J.] Catalan Inst Oncol, Canc Epidemiol Res Program, Unit Nutr Environm & Canc, Barcelona, Spain.
[Tjonneland, Anne; Friis, Soren] Danish Canc Soc, Inst Canc Epidemiol, Copenhagen, Denmark.
[Yang, Ping] Mayo Clin, Rochester, MN USA.
[Wichmann, H-Erich; Heinrich, Joachim] Helmholtz Ctr Munich, Inst Epidemiol, Munich, Germany.
[Wichmann, H-Erich] Univ Munich, Chair Epidemiol, Inst Med Informat Biometry & Epidemiol, Munich, Germany.
[Wichmann, H-Erich] Univ Munich, Klinikum Grosshadern, D-8000 Munich, Germany.
[Szeszenia-Dabrowska, Neonila] Inst Occupat Med, Dept Epidemiol, Lodz, Poland.
[Lissowska, Jolanta] Maria Sklodowska Curie Mem Canc Ctr, Dept Canc Epidemiol & Prevent, Warsaw, Poland.
[Lissowska, Jolanta] Inst Oncol, Warsaw, Poland.
[Zaridze, David] Russian Acad Med Sci, Canc Res Ctr, Inst Carcinogenesis, Moscow, Russia.
[Rudnai, Peter] Fodor Jozsef Natl Ctr Publ Hlth, Natl Inst Environm Hlth, Budapest, Hungary.
[Fabianova, Eleonora] Specialized State Hlth Inst, Dept Occupat Hlth, Banska Bystrica, Slovakia.
[Janout, Vladimir] Palacky Univ, Dept Prevent Med, Fac Med, CR-77147 Olomouc, Czech Republic.
[Bencko, Vladimir] Charles Univ Prague, Fac Med 1, Inst Hyg & Epidemiol, Prague, Czech Republic.
[Brennan, Paul] Int Agcy Res Canc, F-69372 Lyon, France.
[Mates, Dana] Univ Med & Pharm Carol Davila, Bucharest, Romania.
[Schwartz, Ann G.; Cote, Michele L.] Wayne State Univ, Sch Med, Karmanos Canc Inst, Detroit, MI USA.
[Zhang, Zuo-Feng] Univ Calif Los Angeles, Sch Publ Hlth, Dept Epidemiol, Los Angeles, CA 90024 USA.
[Morgenstern, Hal] Univ Michigan, Sch Publ Hlth, Dept Epidemiol, Ann Arbor, MI 48109 USA.
[Morgenstern, Hal] Univ Michigan, Sch Publ Hlth, Dept Environm Hlth Sci, Ann Arbor, MI 48109 USA.
[Morgenstern, Hal] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA.
[Oh, Sam S.] Univ Calif San Francisco, Ctr Tobacco Control Res & Educ, San Francisco, CA 94143 USA.
[Field, John K.] Univ Liverpool, Canc Res Ctr, Roy Castle Lung Canc Res Programme, Liverpool L69 3BX, Merseyside, England.
[Raji, Olaide; Wiencke, John] Univ Calif San Francisco, Dept Neurol Surg, San Francisco, CA USA.
[LeMarchand, Loic] Univ Hawaii, Canc Res Ctr Hawaii, Honolulu, HI 96813 USA.
[Neri, Monica] IRCCS San Raffaele Pisana, Unit Clin & Mol Epidemiol, Rome, Italy.
[Andrew, Angeline S.] Dartmouth Med Sch, Norris Cotton Canc Ctr, Unit Biostat & Epidemiol, Dept Community & Family Med, Lebanon, NH USA.
[Lan, Qing] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Hu, Wei] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, New York, NY 10021 USA.
[Orlow, Irene; Park, Bernard J.] Mem Sloan Kettering Canc Ctr, Dept Surg, New York, NY 10021 USA.
[Boffetta, Paolo] Mt Sinai Sch Med, Tisch Canc Inst, New York, NY USA.
[Boffetta, Paolo] Mt Sinai Sch Med, Inst Transit Epidemiol, New York, NY USA.
[Hung, Rayjean J.] Int Prevent Res Inst, Lyon, France.
RP Rosenberger, A (reprint author), Univ Med Gottingen, Abt Genet Epidemiol, Humboldtallee 32, D-37073 Gottingen, Germany.
EM arosenb@gwdg.de; rayjean.hung@lunenfeld.ca
RI Hung, Rayjean/A-7439-2013; McLaughlin, John/E-4577-2013; Zaridze,
David/K-5605-2013; Hu, Wei/M-3524-2013; Janout, Vladimir/M-5133-2014;
Szeszenia-Dabrowska, Neonila/F-7190-2010; Neri, Monica/J-6308-2012;
OI Orlow, Irene/0000-0001-6234-6961; Neri, Monica/0000-0003-4796-3675;
Duell, Eric J/0000-0001-5256-0163; mates, dana/0000-0002-6219-9807;
Lissowska, Jolanta/0000-0003-2695-5799; Field, John/0000-0003-3951-6365;
bonassi, stefano/0000-0003-3833-6717
FU National Institute of Health [1U19CA148127-01, HIN-CA77118, NIH-CA80127,
R01CA060691, NIH R01CA87895, NIH N01-PC35145, NIH P30CA22453]; German
Research Foundation [GRK1034]; Canadian Cancer Society [CCSRI 020214];
Cancer Care Ontario Research Chair Award; Mayo Clinic (MAYO): Mayo
Foundation Fund; Roy Castle Lung Cancer Foundation UK; Memorial
Sloan-Kettering Cancer Center (MSKCC); Labrecque Foundation; Society of
MSKCC; World Cancer Research Fund; European Commission [IC15-CT96-0313];
Polish State Committee for Scientific Research
[SPUB-M-COPERNICUS/P-05/DZ-30/99/2000]; Wayne State University; Karmanos
Cancer Institute [WSU/KCI-1, WSU/KCI-2]; University of California, San
Francisco (UCSF): National Institutes of Environmental Health Sciences
[ES06717]; NCI [CA-113710]; Danish Diet Cancer and Health Study (DDCHS);
Danish Cancer Society; Helmholtz lung cancer study: German Federal
Ministry of Education, Science, Research and Technology, State of
Bavaria, National Genome Research Network, German Research Foundation
[BI 576/2-1, BI 576/2-2]; Helmholtz Association; Federal office for
Radiation Protection [STSch4454]
FX National Institute of Health (1U19CA148127-01); the German Research
Foundation (GRK1034); the Canadian Cancer Society (CCSRI 020214); Cancer
Care Ontario Research Chair Award. The individual studies were supported
by the following sources:; Mayo Clinic (MAYO): Mayo Foundation Fund and
National Institute of Health (HIN-CA77118, NIH-CA80127 to P.Y.];
Liverpool Lung Project (LLP): Roy Castle Lung Cancer Foundation UK;
Study of the Memorial Sloan-Kettering Cancer Center (MSKCC): Steps for
Breath, the Labrecque Foundation and the Society of MSKCC; Central
Europe study (CE): World Cancer Research Fund and the European
Commission's INCO-COPERNICUS Program (contract number IC15-CT96-0313);
The Warsaw part of CE: The Polish State Committee for Scientific
Research (SPUB-M-COPERNICUS/P-05/DZ-30/99/2000); Studies of the Wayne
State University, Karmanos Cancer Institute (WSU/KCI-1, WSU/KCI-2):
National Institute of Health (R01CA060691, NIH R01CA87895, NIH
N01-PC35145, NIH P30CA22453); Study of the University of California, San
Francisco (UCSF): National Institutes of Environmental Health Sciences
(ES06717); NCI (CA-113710 to S.S.O); Danish Diet Cancer and Health Study
(DDCHS): Danish Cancer Society; Helmholtz lung cancer study: German
Federal Ministry of Education, Science, Research and Technology, State
of Bavaria, National Genome Research Network, German Research Foundation
(BI 576/2-1, BI 576/2-2); Helmholtz Association and the Federal office
for Radiation Protection (STSch4454).
NR 96
TC 24
Z9 24
U1 2
U2 11
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 MAR
PY 2012
VL 33
IS 3
BP 587
EP 597
DI 10.1093/carcin/bgr307
PG 11
WC Oncology
SC Oncology
GA 901SW
UT WOS:000300988100014
PM 22198214
ER
PT J
AU Wellems, TE
Fairhurst, RM
AF Wellems, Thomas E.
Fairhurst, Rick M.
TI An evolving picture of the interactions between malaria parasites and
their host erythrocytes
SO CELL RESEARCH
LA English
DT Editorial Material
ID FALCIPARUM-INFECTED ERYTHROCYTES; PLASMODIUM-FALCIPARUM; INVASION;
HEMOGLOBIN; BINDING; PROTEIN-1; MEMBRANE; PFRH5
AB In patients with malaria, Plasmodium falciparum parasites multiply to enormous numbers in the bloodstream, initiating processes of erythrocyte destruction, endothelial activation and microvascular inflammation that cause devastating pathological effects on host tissues and organs. Recent research casts new light on a mechanism by which hemoglobin mutations may protect against these effects, and on a critical receptor-ligand interaction that provides fresh opportunities for the development of vaccines against blood-stage infection.
C1 [Wellems, Thomas E.; Fairhurst, Rick M.] NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA.
RP Wellems, TE (reprint author), NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA.
EM twellems@niaid.nih.gov
NR 18
TC 1
Z9 1
U1 0
U2 7
PU INST BIOCHEMISTRY & CELL BIOLOGY
PI SHANGHAI
PA SIBS, CAS, 319 YUEYAND ROAD, SHANGHAI, 200031, PEOPLES R CHINA
SN 1001-0602
J9 CELL RES
JI Cell Res.
PD MAR
PY 2012
VL 22
IS 3
BP 453
EP 456
DI 10.1038/cr.2012.14
PG 4
WC Cell Biology
SC Cell Biology
GA 901DR
UT WOS:000300942400004
PM 22270182
ER
PT J
AU Chepelev, I
Wei, G
Wangsa, D
Tang, QS
Zhao, KJ
AF Chepelev, Iouri
Wei, Gang
Wangsa, Dara
Tang, Qingsong
Zhao, Keji
TI Characterization of genome-wide enhancer-promoter interactions reveals
co-expression of interacting genes and modes of higher order chromatin
organization
SO CELL RESEARCH
LA English
DT Article
DE chromatin interactions; enhancers; promoters; ChIA-PET; 3C; H3K4me2
ID CCCTC-BINDING FACTOR; BETA-GLOBIN LOCUS; CHIP-SEQ DATA; TRANSCRIPTION;
CTCF; SITES; EXPRESSION; DOMAINS; CELLS; METHYLATIONS
AB Recent epigenomic studies have predicted thousands of potential enhancers in the human genome. However, there has not been systematic characterization of target promoters for these potential enhancers. Using H3K4me2 as a mark for active enhancers, we identified genome-wide EP interactions in human CD4(+) T cells. Among the 6 520 long-distance chromatin interactions, we identify 2 067 enhancers that interact with 1 619 promoters and enhance their expression. These enhancers exist in accessible chromatin regions and are associated with various histone modifications and polymerase II binding. The promoters with interacting enhancers are expressed at higher levels than those without interacting enhancers, and their expression levels are positively correlated with the number of interacting enhancers. Interestingly, interacting promoters are co-expressed in a tissue-specific manner. We also find that chromosomes are organized into multiple levels of interacting domains. Our results define a global view of EP interactions and provide a data set to further understand mechanisms of enhancer targeting and long-range chromatin organization. The Gene Expression Omnibus accession number for the raw and analyzed chromatin interaction data is GSE32677.
C1 [Chepelev, Iouri; Wei, Gang; Tang, Qingsong; Zhao, Keji] NHLBI, Syst Biol Ctr, Bethesda, MD 20892 USA.
[Wangsa, Dara] NCI, Sect Canc Genom, NIH, Bethesda, MD 20892 USA.
RP Zhao, KJ (reprint author), NHLBI, Syst Biol Ctr, Bethesda, MD 20892 USA.
EM zhaok@nhlbi.nih.gov
FU Division of Intramural Research, NHLBI, National Institutes of Health,
USA
FX We thank our colleagues Brian Abraham, Alika Maunakea and Daniel
Kraushaar for critical reading of the manuscript and Thomas Ried for
suggestions. The paired-end sequencing was performed by the DNA
Sequencing Core Facility of National Heart, Lung and Blood Institute
(NHLBI). This work was supported by the Division of Intramural Research,
NHLBI, National Institutes of Health, USA.
NR 48
TC 77
Z9 79
U1 5
U2 22
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 MAR
PY 2012
VL 22
IS 3
BP 490
EP 503
DI 10.1038/cr.2012.15
PG 14
WC Cell Biology
SC Cell Biology
GA 901DR
UT WOS:000300942400007
PM 22270183
ER
PT J
AU Leung, JYK
Bennett, WR
Herbert, RP
West, AK
Lee, PR
Wake, H
Fields, RD
Chuah, MI
Chung, RS
AF Leung, Jacqueline Y. K.
Bennett, William R.
Herbert, Rosalind P.
West, Adrian K.
Lee, Philip R.
Wake, Hiroaki
Fields, R. Douglas
Chuah, Meng Inn
Chung, Roger S.
TI Metallothionein promotes regenerative axonal sprouting of dorsal root
ganglion neurons after physical axotomy
SO CELLULAR AND MOLECULAR LIFE SCIENCES
LA English
DT Article
DE Metallothionein; Neuronal injury; Neurite sprouting; Megalin; Dorsal
root ganglion neurons
ID NEURITE GROWTH; MEGALIN; RECEPTORS; PROTEIN; INJURY; FAMILY; ROLES;
BRAIN
AB Prior studies have reported that metallothionein I/II (MT) promote regenerative axonal sprouting and neurite elongation of a variety of central nervous system neurons after injury. In this study, we evaluated whether MT is capable of modulating regenerative axon outgrowth of neurons from the peripheral nervous system. The effect of MT was firstly investigated in dorsal root ganglion (DRG) explants, where axons were scratch-injured in the presence or absence of exogenous MT. The application of MT led to a significant increase in regenerative sprouting of neurons 16 h after injury. We show that the pro-regenerative effect of MT involves an interaction with the low-density lipoprotein receptor megalin, which could be blocked using the competitive antagonist RAP. Pre-treatment with the mitogen-activated protein kinase (MAPK) inhibitor PD98059 also completely abrogated the effect of exogenous MT in promoting axonal outgrowth. Interestingly, we only observed megalin expression in neuronal soma and not axons in the DRG explants. To investigate this matter, an in vitro injury model was established using Campenot chambers, which allowed the application of MT selectively into either the axonal or cell body compartments after scratch injury was performed to axons. At 16 h after injury, regenerating axons were significantly longer only when exogenous MT was applied solely to the soma compartment, in accordance with the localized expression of megalin in neuronal cell bodies. This study provides a clear indication that MT promotes axonal regeneration of DRG neurons, via a megalin-and MAPK-dependent mechanism.
C1 [Leung, Jacqueline Y. K.; Bennett, William R.; Herbert, Rosalind P.; West, Adrian K.; Chuah, Meng Inn; Chung, Roger S.] Univ Tasmania, Menzies Res Inst, Hobart, Tas 7001, Australia.
[Lee, Philip R.; Wake, Hiroaki; Fields, R. Douglas] NICHHD, NIH, Bethesda, MD 20892 USA.
RP Chung, RS (reprint author), Univ Tasmania, Menzies Res Inst, Private Bag 24, Hobart, Tas 7001, Australia.
EM rschung@utas.edu.au
RI Chuah, Meng Inn/J-7671-2014
FU Australian Research Council [DP0984673]; National Health and Medical
Research Council of Australia [544913]; Motor Accident and Insurance
Board of Tasmania; Australian Academy of Sciences
FX This research was supported by research grants from the Australian
Research Council (DP0984673), the National Health and Medical Research
Council of Australia (ID#544913), and the Motor Accident and Insurance
Board of Tasmania. JYKL also received a travel fellowship from the
Australian Academy of Sciences to visit the NIH (USA) to undertake some
of the experiments reported in this study.
NR 14
TC 6
Z9 7
U1 0
U2 5
PU SPRINGER BASEL AG
PI BASEL
PA PICASSOPLATZ 4, BASEL, 4052, SWITZERLAND
SN 1420-682X
J9 CELL MOL LIFE SCI
JI Cell. Mol. Life Sci.
PD MAR
PY 2012
VL 69
IS 5
BP 809
EP 817
DI 10.1007/s00018-011-0790-7
PG 9
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 898IR
UT WOS:000300736400010
PM 21833580
ER
PT J
AU Kim, WG
Guigon, CJ
Fozzatti, L
Park, JW
Lu, CX
Willingham, MC
Cheng, SY
AF Kim, Won Gu
Guigon, Celine J.
Fozzatti, Laura
Park, Jeong Won
Lu, Changxue
Willingham, Mark C.
Cheng, Sheue-yann
TI SKI-606, an Src Inhibitor, Reduces Tumor Growth, Invasion, and Distant
Metastasis in a Mouse Model of Thyroid Cancer
SO CLINICAL CANCER RESEARCH
LA English
DT Article
ID FOCAL ADHESION KINASE; BREAST-CANCER; IN-VIVO; SOLID MALIGNANCIES;
PROSTATE-CANCER; TARGETING SRC; CELL-ADHESION; E-CADHERIN; CARCINOMA;
PROGRESSION
AB Purpose: Src is overexpressed or hyperactivated in a variety of human cancers, including thyroid carcinoma. Src is a central mediator in multiple signaling pathways that are important in oncogenesis and cancer progression. In this study, we evaluated the effects of an Src inhibitor, SKI-606 (bosutinib), in a spontaneous metastatic thyroid cancer model with constitutively activated Src (Thrb(PV/PV) Pten(+/-) mice).
Experimental Design: Thrb(PV/PV) Pten(+/-) mice were treated with SKI-606 or vehicle controls, beginning at 6 weeks of age until the mice succumbed to thyroid cancer. We assessed the effects of SKI-606 on thyroid cancer progression and analyzed the impact of SKI-606 on aberrant Src-mediated signaling.
Results: SKI-606 effectively inhibited aberrant activation of Src and its downstream targets to markedly inhibit the growth of thyroid tumor, thereby prolonging the survival of treated mice. While Src inhibition did not induce cell apoptosis, it decreased cell proliferation by affecting the expression of key regulators of cell-cycle progression. Importantly, SKI-606 dramatically prevented dedifferentiation, vascular invasion, and lung metastasis of thyroid cancer cells. These responses were meditated by downregulation of mitogen-activated protein kinase pathways and inhibition of the epithelial-mesenchymal transition.
Conclusions: Our findings suggest that Src is critical in the progression of thyroid cancer, making oral SKI-606 a promising treatment strategy for refractory thyroid cancer. Clin Cancer Res; 18(5); 1281-90. (C)2012 AACR.
C1 [Cheng, Sheue-yann] NCI, Gene Regulat Sect, Mol Biol Lab, Ctr Canc Res, Bethesda, MD 20892 USA.
[Willingham, Mark C.] Wake Forest Univ, Dept Pathol, Winston Salem, NC 27109 USA.
RP Cheng, SY (reprint author), NCI, Gene Regulat Sect, Mol Biol Lab, Ctr Canc Res, 37 Convent Dr,Room 5128, Bethesda, MD 20892 USA.
EM chengs@mail.nih.gov
OI Kim, Won Gu/0000-0002-8404-7759
FU Center for Cancer Research; National Cancer Institute,; NIH
FX The present research was supported by the Intramural Research Program at
the Center for Cancer Research, National Cancer Institute, NIH.
NR 38
TC 17
Z9 17
U1 0
U2 3
PU AMER ASSOC CANCER RESEARCH
PI PHILADELPHIA
PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA
SN 1078-0432
EI 1557-3265
J9 CLIN CANCER RES
JI Clin. Cancer Res.
PD MAR 1
PY 2012
VL 18
IS 5
BP 1281
EP 1290
DI 10.1158/1078-0432.CCR-11-2892
PG 10
WC Oncology
SC Oncology
GA 902LW
UT WOS:000301040700012
PM 22271876
ER
PT J
AU Kim, JW
Madan, RA
Gulley, JL
AF Kim, Joseph W.
Madan, Ravi A.
Gulley, James L.
TI Initial PSA Oscillations Precede Prolonged Stable Disease in a Patient
Treated With a Therapeutic Cancer Vaccine
SO CLINICAL GENITOURINARY CANCER
LA English
DT Article
DE Immunologic response; Prostate Cancer; PROSTVAC; PSA-TRICOM
ID RESISTANT PROSTATE-CANCER; SURVIVAL; IMMUNOTHERAPY; MEN
AB Clinical Practice Points
center dot In the absence of symptomatic or radiographic evidence of disease progression, the decision to change treatment in patients with metastatic castration-resistant prostate cancer (mCRPC) should not be based solely on changes in PSA values. This is especially true for immune-based therapies, such as Vaccines, In Which Short-term Changes In Progression Are Often Not seen.
center dot Phase II Data Suggest That PSA-TRICOM, a Therapeutic Cancer Vaccine, Can Improve Long-term Clinical Outcomes With Minimal Toxicity In Patients With mCRPC.
center dot PSA-TRICOM Will Be Prospectively Evaluated In a Phase III, Double-blind, Placebo-controlled Clinical Trial In 1200 Patients With mCRPC, With Overall Survival As the Primary Endpoint.
C1 [Kim, Joseph W.; Madan, Ravi A.; Gulley, James L.] NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Kim, Joseph W.; Madan, Ravi A.; Gulley, James L.] NCI, Med Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
RP Gulley, JL (reprint author), NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, NIH, 10 Ctr Dr,Rm 13N208,MSC-1750, Bethesda, MD 20892 USA.
EM gulleyj@mail.nih.gov
RI Gulley, James/K-4139-2016
OI Gulley, James/0000-0002-6569-2912
FU Intramural NIH HHS [Z01 BC010666-04]
NR 15
TC 2
Z9 2
U1 0
U2 0
PU CIG MEDIA GROUP, LP
PI DALLAS
PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA
SN 1558-7673
J9 CLIN GENITOURIN CANC
JI Clin. Genitourin. Cancer
PD MAR
PY 2012
VL 10
IS 1
BP 43
EP 46
DI 10.1016/j.clgc.2011.09.003
PG 4
WC Oncology; Urology & Nephrology
SC Oncology; Urology & Nephrology
GA 902KG
UT WOS:000301036400008
PM 22019260
ER
PT J
AU McEwing, R
Kitchener, AC
Holleley, C
Kilshaw, K
O'Donoghue, P
AF McEwing, Ross
Kitchener, Andrew C.
Holleley, Clare
Kilshaw, Kerry
O'Donoghue, Paul
TI An allelic discrimination SNP assay for distinguishing the mitochondrial
lineages of European wildcats and domestic cats
SO CONSERVATION GENETICS RESOURCES
LA English
DT Article
DE Wildcat; SNP; Introgression; Felis silvestris
ID SCOTTISH WILDCAT
AB Here we present an allelic discrimination assay designed to distinguish European wildcat mtDNA lineages from those of the domestic cat. Introgression between the native wildcat and introduced domestic cat has the potential to limit and reduce the recent recovery of remnant populations. Applied conservation genetic techniques can aid current conservation decisions on lethal control and neutering measures in hybrid zones. This real-time PCR technique offers a rapid, inexpensive and reliable assay to assess mtDNA introgression in the wild and has already identified hybrid individuals in the Scottish wildcat captive breeding programme.
C1 [McEwing, Ross] Royal Zool Soc Scotland, WildGenes Lab, Edinburgh EH12 6TS, Midlothian, Scotland.
[Kitchener, Andrew C.] Natl Museum Scotland, Dept Nat Sci, Edinburgh EH1 1JF, Midlothian, Scotland.
[Holleley, Clare] NCI, Lab Genom Div, Frederick, MD 21702 USA.
[Kilshaw, Kerry] Univ Oxford, Wildlife Conservat Res Unit, Dept Zool, Oxford OX13 5QL, Oxon, England.
[O'Donoghue, Paul] Univ Chester, Dept Biol Sci, Chester CH1 4BJ, Cheshire, England.
RP McEwing, R (reprint author), Royal Zool Soc Scotland, WildGenes Lab, 134 Corstorphine Rd, Edinburgh EH12 6TS, Midlothian, Scotland.
EM rmcewing@rzss.org.uk
RI Holleley, Clare/C-4629-2011
OI Holleley, Clare/0000-0002-5257-0019
FU Royal Zoological Society of Scotland
FX The authors are grateful to Neville Buck, Douglas Richardson, David
Hetherington, Steve Piper and Rob Ogden. The work was funded by the
Royal Zoological Society of Scotland.
NR 6
TC 1
Z9 1
U1 1
U2 51
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 1877-7252
J9 CONSERV GENET RESOUR
JI Conserv. Genet. Resour.
PD MAR
PY 2012
VL 4
IS 1
BP 163
EP 165
DI 10.1007/s12686-011-9499-z
PG 3
WC Biodiversity Conservation; Genetics & Heredity
SC Biodiversity & Conservation; Genetics & Heredity
GA 898WG
UT WOS:000300772500039
ER
PT J
AU Nguyen, SA
Walker, D
Gillespie, MB
Gutkind, JS
Day, TA
AF Nguyen, Shaun A.
Walker, David
Gillespie, M. Boyd
Gutkind, J. Silvio
Day, Terry A.
TI mTOR Inhibitors and its Role in the Treatment of Head and Neck Squamous
Cell Carcinoma
SO CURRENT TREATMENT OPTIONS IN ONCOLOGY
LA English
DT Article
DE mTOR inhibitors; temsirolimus; everolimus; deforolimus; head and neck
squamous cell carcinomas
ID PHASE-I TRIAL; MAMMALIAN TARGET; ADVANCED MALIGNANCIES; AKT/MAMMALIAN
TARGET; SIROLIMUS RAPAMYCIN; CANCER-THERAPY; PATHWAY; EVEROLIMUS;
PHOSPHORYLATION; ACTIVATION
AB Head and neck squamous cell carcinomas (HNSCC) represent 6% of all cancers diagnosed each year in the United States, affecting approximately 43,000 new patients and resulting in approximately 12,000 deaths. Currently, three main rapalogs exist for the treatment of cancer: CCI-779 (temsirolimus), RAD001 (everolimus), and AP235373 (deforolimus). Clinicians managing HNSCC need to be aware of the three rapalogs. Extensive evidence has shown rapamycin-analogs to be effective agents in the treatment of a number of solid tumors. While extensive preclinical data suggests that HNSCC would be an appropriate tumor type to benefit from inhibition of the mTOR pathway, limited clinical data is yet available to support this. Numerous phase II trials evaluating mTOR inhibitors for use in HNSCC are currently recruiting patients.
C1 [Nguyen, Shaun A.; Walker, David; Gillespie, M. Boyd; Day, Terry A.] Med Univ S Carolina, Dept Otolaryngol Head & Neck Surg, Charleston, SC 29425 USA.
[Walker, David] Rush Med Coll, Chicago, IL 60612 USA.
[Gutkind, J. Silvio] Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA.
RP Nguyen, SA (reprint author), Med Univ S Carolina, Dept Otolaryngol Head & Neck Surg, Charleston, SC 29425 USA.
EM nguyensh@musc.edu
NR 35
TC 26
Z9 26
U1 0
U2 5
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1527-2729
J9 CURR TREAT OPTION ON
JI Curr. Treat. Options Oncol.
PD MAR
PY 2012
VL 13
IS 1
BP 71
EP 81
DI 10.1007/s11864-011-0180-2
PG 11
WC Oncology
SC Oncology
GA 898WK
UT WOS:000300772900007
PM 22282394
ER
PT J
AU Yaguchi, J
Angerer, LM
Inaba, K
Yaguchi, S
AF Yaguchi, Junko
Angerer, Lynne M.
Inaba, Kazuo
Yaguchi, Shunsuke
TI Zinc finger homeobox is required for the differentiation of serotonergic
neurons in the sea urchin embryo
SO DEVELOPMENTAL BIOLOGY
LA English
DT Article
DE Neurogenesis; Serotonin; FoxQ2; Nodal; Delta; Notch; Lateral inhibition
ID ORAL-ABORAL AXIS; NERVOUS-SYSTEM; STRONGYLOCENTROTUS-PURPURATUS;
STEM-CELLS; C-ELEGANS; EXPRESSION PATTERNS; NEURAL INDUCTION;
BETA-CATENIN; ANIMAL PLATE; GENE
AB Serotonergic neurons differentiate in the neurogenic animal plate ectoderm of the sea urchin embryo. The regulatory mechanisms that control the specification or differentiation of these neurons in the sea urchin embryo are not yet understood, although, after the genome was sequenced, many genes encoding transcription factors expressed in this region were identified. Here, we report that zinc finger homeobox (zfhx1/z81) is expressed in serotonergic neural precursor cells, using double in situ hybridization screening with a serotonergic neural marker, tryptophan 5-hydroxylase (tph) encoding a serotonin synthase that is required for the differentiation of serotonergic neurons. zfhx1/z81 begins to be expressed at gastrula stage in individual cells in the anterior neuroectoderm, some of which also express delta. zfhx1/z81 expression gradually disappears as neural differentiation begins with tph expression. When the translation of Zfhx1/Z81 is blocked by morpholino injection, embryos express neither tph nor the neural marker synaptotagminB in cells of the animal plate, and serotonergic neurons do not differentiate. In contrast, Zfhx1/Z81 morphants do express fez, another neural precursor marker, which appears to function in the initial phase of specification/differentiation of serotonergic neurons. In addition, zfhx1/z81 is one of the targets suppressed in the animal plate by anti-neural signals such as Nodal as well as Delta-Notch. We conclude that Zfhx1/Z81 functions during the specification of individual anterior neural precursors and promotes the expression of tph and synaptotagminB, required for the differentiation of serotonergic neurons. (C) 2011 Elsevier Inc. All rights reserved.
C1 [Yaguchi, Junko; Inaba, Kazuo; Yaguchi, Shunsuke] Univ Tsukuba, Shimoda Marine Res Ctr, Shizuoka 4150025, Japan.
[Yaguchi, Junko; Yaguchi, Shunsuke] Univ Tsukuba, Initiat Promot Young Scientists Independent Res, Shizuoka 4150025, Japan.
[Angerer, Lynne M.] Natl Inst Dent & Craniofacial Res, Dev Mech Sect, NIH, Bethesda, MD 20892 USA.
RP Yaguchi, S (reprint author), Univ Tsukuba, Shimoda Marine Res Ctr, 5-10-1 Shimoda, Shizuoka 4150025, Japan.
EM yag@kurofune.shimoda.tsukuba.ac.jp
OI Yaguchi, Shunsuke/0000-0002-8326-5762
FU Ministry of Education, Culture, Sports, Science and Technology of the
Japanese Government (MEXT) [22370023]; Takeda Science Foundation; MEXT
[22370023]; National Institutes of Health, National Institute for Dental
and Craniofacial Research; [21770227]; [23770241]; [23-3584]
FX We thank Robert Angerer for fruitful comments on this manuscript and
Robert Burke, Yoko Nakajima, and David McClay for essential reagents. We
thank Masato Kiyomoto and Mamoru Yamaguchi for providing the adult sea
urchins and Mrs. Y. Tsuchiya, T. Sato, H, Shinagawa, and Y. Yamada,
Shimoda Marine Research Center, for collecting and keeping the adult sea
urchins. This work was supported, in part, by Special Coordination Funds
for Promoting Science and Technology of the Ministry of Education,
Culture, Sports, Science and Technology of the Japanese Government
(MEXT), by Grant-in Aid for Young Scientists (B No. 21770227 and No.
23770241), and Takeda Science Foundation to S.Y., in part by MEXT (No.
22370023) to K.I., and in part by the Intramural Program of the National
Institutes of Health, National Institute for Dental and Craniofacial
Research, to L.M.A. J.Y. was a Predoctoral Fellow of JSPS with research
grant (23-3584).
NR 54
TC 9
Z9 9
U1 2
U2 12
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0012-1606
J9 DEV BIOL
JI Dev. Biol.
PD MAR 1
PY 2012
VL 363
IS 1
BP 74
EP 83
DI 10.1016/j.ydbio.2011.12.024
PG 10
WC Developmental Biology
SC Developmental Biology
GA 900AA
UT WOS:000300857800007
PM 22210002
ER
PT J
AU Galanopoulou, AS
Buckmaster, PS
Staley, KJ
Moshe, SL
Perucca, E
Engel, J
Loscher, W
Noebels, JL
Pitkanen, A
Stables, J
White, HS
O'Brien, TJ
Simonato, M
AF Galanopoulou, Aristea S.
Buckmaster, Paul S.
Staley, Kevin J.
Moshe, Solomon L.
Perucca, Emilio
Engel, Jerome, Jr.
Loescher, Wolfgang
Noebels, Jeffrey L.
Pitkanen, Asla
Stables, James
White, H. Steve
O'Brien, Terence J.
Simonato, Michele
CA Amer Epilepsy Soc Basic Sci Comm
Int League Epilepsy Working Grp
TI Identification of new epilepsy treatments: Issues in preclinical
methodology
SO EPILEPSIA
LA English
DT Article
DE Antiseizure drug; Antiepileptogenesis; Disease modification;
Comorbidities; Biomarkers
ID TEMPORAL-LOBE EPILEPSY; INFANTILE SPASMS; ANTIEPILEPTIC DRUGS;
PERSISTENT SEIZURES; FUTURE-DIRECTIONS; FEBRILE SEIZURES; ANIMAL-MODEL;
RODENT MODEL; MOUSE MODEL; EPILEPTOGENESIS
AB Preclinical research has facilitated the discovery of valuable drugs for the symptomatic treatment of epilepsy. Yet, despite these therapies, seizures are not adequately controlled in a third of all affected individuals, and comorbidities still impose a major burden on quality of life. The introduction of multiple new therapies into clinical use over the past two decades has done little to change this. There is an urgent demand to address the unmet clinical needs for: (1) new symptomatic antiseizure treatments for drug-resistant seizures with improved efficacy/tolerability profiles, (2) disease-modifying treatments that prevent or ameliorate the process of epileptogenesis, and (3) treatments for the common comorbidities that contribute to disability in people with epilepsy. New therapies also need to address the special needs of certain subpopulations, that is, age- or gender-specific treatments. Preclinical development in these treatment areas is complex due to heterogeneity in presentation and etiology, and may need to be formulated with a specific seizure, epilepsy syndrome, or comorbidity in mind. The aim of this report is to provide a framework that will help define future guidelines that improve and standardize the design, reporting, and validation of data across preclinical antiepilepsy therapy development studies targeting drug-resistant seizures, epileptogenesis, and comorbidities.
C1 [Galanopoulou, Aristea S.; Moshe, Solomon L.] Albert Einstein Coll Med, Dominick P Purpura Dept Neurosci, Saul R Korey Dept Neurol, Lab Dev Epilepsy,Montefiore Einstein Epilepsy Man, Bronx, NY 10461 USA.
[Buckmaster, Paul S.] Stanford Univ, Dept Comparat Med & Neurol, Stanford, CA 94305 USA.
[Buckmaster, Paul S.] Stanford Univ, Dept Neurol Sci, Stanford, CA 94305 USA.
[Staley, Kevin J.] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA.
[Staley, Kevin J.] Harvard Univ, Sch Med, Boston, MA USA.
[Moshe, Solomon L.] Albert Einstein Coll Med, Dept Pediat, Bronx, NY 10461 USA.
[Perucca, Emilio] Univ Pavia, Dept Internal Med & Therapeut, Clin Pharmacol Unit, I-27100 Pavia, Italy.
[Perucca, Emilio] IRCCS C Mondino Fdn, Natl Neurol Inst, Pavia, Italy.
[Engel, Jerome, Jr.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA.
[Engel, Jerome, Jr.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurobiol, Los Angeles, CA 90095 USA.
[Engel, Jerome, Jr.] Univ Calif Los Angeles, David Geffen Sch Med, Dept Psychiat & Behav Sci, Los Angeles, CA 90095 USA.
[Engel, Jerome, Jr.] Univ Calif Los Angeles, David Geffen Sch Med, Brain Res Inst, Los Angeles, CA 90095 USA.
[Loescher, Wolfgang] Univ Vet Med, Dept Pharmacol Toxicol & Pharm, Hannover, Germany.
[Noebels, Jeffrey L.] Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA.
[Pitkanen, Asla] Univ Eastern Finland, AI Virtanen Inst Mol Sci, Epilepsy Res Lab, Kuopio, Finland.
[Pitkanen, Asla] Kuopio Univ Hosp, Dept Neurol, SF-70210 Kuopio, Finland.
[Stables, James] NINDS, ASP, NIH, Bethesda, MD 20892 USA.
[White, H. Steve] Univ Utah, Dept Pharmacol & Toxicol, Salt Lake City, UT 84112 USA.
[O'Brien, Terence J.] Univ Melbourne, Dept Med, Royal Melbourne Hosp, Parkville, Vic 3052, Australia.
[O'Brien, Terence J.] Univ Melbourne, Royal Melbourne Hosp, Dept Neurol, Parkville, Vic, Australia.
[Simonato, Michele] Univ Ferrara, Dept Clin & Expt Med, Pharmacol Sect, I-44100 Ferrara, Italy.
[Simonato, Michele] Univ Ferrara, Ctr Neurosci, I-44100 Ferrara, Italy.
[Simonato, Michele] Natl Inst Neurosci, Palermo, Italy.
RP Galanopoulou, AS (reprint author), Albert Einstein Coll Med, Dominick P Purpura Dept Neurosci, Saul R Korey Dept Neurol, Lab Dev Epilepsy,Montefiore Einstein Epilepsy Man, 1410 Pelham Pkwy S,Kennedy Ctr Rm 306, Bronx, NY 10461 USA.
EM aristea.galanopoulou@einstein.yu.edu
RI French, Jacqueline/G-6795-2013; O'Brien, Terence/L-8102-2013;
OI Noebels, Jeffrey /0000-0002-2887-0839; French,
Jacqueline/0000-0003-2242-8027; O'Brien, Terence/0000-0002-7198-8621
FU NIH NINDS/NICHD [NS62947]; Johnson Johnson; Novartis; NIH [R01 NS20253,
R01-NS43209, 2UO1-NS45911, P01 NS02808, R01 NS33310, U01 NS42372];
Heffer Family Foundation; Eisai; GlaxoSmithKline; Bial; Pfizer; UCB
Pharma; Upsher-Smith; Vertex; Italian Ministry of Health; Italian
Ministry for University and Research; Italian Medicines Agency; European
Commission of the EU; NeuroAdjuvants, Inc.; Janssen-Cilag;
Sanofi-Synthelabo; Chiesi Pharmaceuticals (Italy); Schering-Plough
FX ASG has received research support from NIH NINDS/NICHD grant NS62947
(PI) and recent research grant by Johnson & Johnson. ASG has also
received consultancy fees from Novartis and royalties from Morgan and
Claypool Life Sciences. PSB has nothing to disclose. KJS has nothing to
disclose. SLM has received research support from NIH: R01 NS20253 (PI),
R01-NS43209 (Investigator), 2UO1-NS45911 (Investigator), and the Heffer
Family Foundation. SLM is serving on the Editorial Board of Neurobiology
of Disease, Epileptic Disorders, Brain and Development, and
Physiological Research and has received a consultancy fee from Eisai and
speaker's fee and travel from GlaxoSmithKline. EP received speaker's or
consultancy fees and/or research grants from Bial, Eisai,
GlaxoSmithKline, Johnson & Johnson, Novartis, Pfizer, Pfizer, UCB
Pharma, Upsher-Smith, and Vertex. EP receives research support from the
Italian Ministry of Health, the Italian Ministry for University and
Research, the Italian Medicines Agency, and the European Commission of
the EU. EP also serves on the editorial boards of Acta Neurologica
Scandinavica, CNS Drugs, Epileptic Disorders, Epilepsy Research,
Seizure, Lancet Neurology, Expert Reviews in Neurotherapeutics, Clinical
Pharmacokinetics, Therapeutic Advances in Drug Safety, Frontiers in
Clinical Trials and Pharmacotherapy, and Clinical Drug Investigation.
JEJr has received research funding from NIH grants P01 NS02808, R01
NS33310, U01 NS42372, honoraria from Medtronic, Eisai, Johnson &
Johnson, Lippincottand royalties from Medlink, Wolters-Kluwer,
Blackwell, and Elsevier. WL has nothing to disclose. JLN has nothing to
disclose. AP has nothing to disclose. JS has nothing to disclose. HSW
has served as a paid consultant to Johnson & Johnson Pharmaceutical
Research and Development, GlaxoSmithKline, Valeant Pharmaceuticals, Eli
Lilly & Co., and Upsher-Smith Laboratories, Inc., is a member of the UCB
Pharma Speakers Bureau, the NeuroTherapeutics Scientific Advisory Board,
has received research funding from NeuroAdjuvants, Inc., and is one of
two scientific cofounders of NeuroAdjuvants, Inc., Salt Lake City, UT.
TJO'B has received unrestricted research grants from UCB Pharma
Janssen-Cilag, Sanofi-Synthelabo, and Novartis. TJO'B has received
speaking honorarium from UCB Pharma Janssen-Cilag, Sanofi-Synthelabo,
and SciGen. MS has received research funding from GlaxoSmithKline,
Chiesi Pharmaceuticals (Italy), Sanofi-Synthelabo, and Schering-Plough.
We confirm that we have read the Journal's position on issues relating
to ethical publication. This statement is consistent with these
guidelines
NR 61
TC 85
Z9 87
U1 1
U2 24
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0013-9580
J9 EPILEPSIA
JI Epilepsia
PD MAR
PY 2012
VL 53
IS 3
BP 571
EP 582
DI 10.1111/j.1528-1167.2011.03391.x
PG 12
WC Clinical Neurology
SC Neurosciences & Neurology
GA 899TF
UT WOS:000300838400023
PM 22292566
ER
PT J
AU Hesdorffer, CS
Malchinkhuu, E
Biragyn, A
Mabrouk, OS
Kennedy, RT
Madara, K
Taub, DD
Longo, DL
Schwartz, JB
Ferrucci, L
Goetzl, EJ
AF Hesdorffer, Charles S.
Malchinkhuu, Enkhzol
Biragyn, Arya
Mabrouk, Omar S.
Kennedy, Robert T.
Madara, Karen
Taub, Dennis D.
Longo, Dan L.
Schwartz, Janice B.
Ferrucci, Luigi
Goetzl, Edward J.
TI Distinctive immunoregulatory effects of adenosine on T cells of older
humans
SO FASEB JOURNAL
LA English
DT Article
DE cytokines; cellular antigens; chemotaxis; immunosenescence;
immunodeficiency
ID IMMUNE SUPPRESSION; LYMPHOCYTES; EXPRESSION; ACTIVATION; CD39; CD73;
INTERLEUKIN-2
AB A role for adenosine in immunosenescence was investigated in T cells from older (>= 65 yr) and younger (24-45 yr) healthy humans. Adenosine concentrations in cultures of activated T cells were significantly higher (P<0.0001) for older (145 +/- 47 nM, mean +/- SD) than younger (58 +/- 5.5 nM) subjects. Expression of the activation coreceptor CD28 was suppressed significantly by 0.1 to 1 mu M exogenous adenosine, with greater effects of 1 mu M (P<0.01) on T cells of younger (mean suppression of 67 and 65% for CD4 and CD8 T cells, respectively) than older (means of 42 and 46%) subjects. T-cell chemotaxis to CCL21 was suppressed significantly by 0.3 and 1 mu M exogenous adenosine, with mean maximum decreases of 39 and 49%, respectively, for younger subjects and 28 and 31% for older subjects. Generation of IL-2 and IFN-gamma by T cells of younger and older subjects was suppressed substantially only at adenosine levels of 3 mu M or higher. Lower baseline expression of CD28 and chemotaxis to CCL21 and S1P for T cells from older subjects attributable to endogenous adenosine were reversed completely by two different A(2A) adenosine receptor antagonists without affecting T cells of younger subjects. Adenosine is an endogenous T-cell immunosuppressor in older humans, and A(2A) antagonists reverse adenosine-induced T-cell deficiencies of aging.-Hesdorffer, H. S., Malchinkhuu, E., Biragyn, A., Mabrouk, O. S., Kennedy, R. T., Madara, K., Taub, D. D., Longo, D. L., Schwartz, J. B., Ferrucci, L., Goetzl, E. J. Distinctive immunoregulatory effects of adenosine on T cells of older humans. FASEB J. 26, 1301-1310 (2012). www.fasebj.org
C1 [Goetzl, Edward J.] JHSF, Geriatr Res Ctr, Geriatr Res Labs, San Francisco, CA 94112 USA.
[Hesdorffer, Charles S.; Malchinkhuu, Enkhzol; Biragyn, Arya; Madara, Karen; Taub, Dennis D.; Longo, Dan L.; Ferrucci, Luigi; Goetzl, Edward J.] NIA, NIH, Baltimore, MD 21224 USA.
[Mabrouk, Omar S.; Kennedy, Robert T.] Univ Michigan, Dept Chem, Ann Arbor, MI 48109 USA.
[Schwartz, Janice B.; Goetzl, Edward J.] Univ Calif San Francisco, Dept Med, San Francisco, CA USA.
RP Goetzl, EJ (reprint author), JHSF, Geriatr Res Ctr, Geriatr Res Labs, 302 Silver Ave, San Francisco, CA 94112 USA.
EM edward.goetzl@ucsf.edu
RI Kennedy, Robert/G-9095-2016
OI Kennedy, Robert/0000-0003-2447-7471
FU U.S. National Institute on Aging; Jewish Home of San Francisco
FX This research was supported by the intramural research program of the
U.S. National Institute on Aging and endowment funds of the Jewish Home
of San Francisco. The authors are grateful to Judith H. Goetzl for
preparation of the figures and tables. C. S. H., E. M., A. B., O.S.M.,
R. T. K., J.B.S., and E.J.G. designed research; C. S. H., K. M., J.B.S.,
and L. F. evaluated and selected subjects; C. S. H., E. M., O.S.M., D.
D. T., and E.J.G. performed laboratory research; C. S. H., E. M.,
O.S.M., D. L. L., L. F., and E.J.G. analyzed data and wrote the paper.
NR 26
TC 5
Z9 5
U1 0
U2 0
PU FEDERATION AMER SOC EXP BIOL
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0892-6638
J9 FASEB J
JI Faseb J.
PD MAR
PY 2012
VL 26
IS 3
BP 1301
EP 1310
DI 10.1096/fj.11-197046
PG 10
WC Biochemistry & Molecular Biology; Biology; Cell Biology
SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other
Topics; Cell Biology
GA 901FY
UT WOS:000300949300032
PM 22121051
ER
PT J
AU Liao, LM
Vaughan, TL
Corley, DA
Cook, MB
Casson, AG
Kamangar, F
Abnet, CC
Risch, HA
Giffen, C
Freedman, ND
Chow, WH
Sadeghi, S
Pandeya, N
Whiteman, DC
Murray, LJ
Bernstein, L
Gammon, MD
Wu, AH
AF Liao, Linda M.
Vaughan, Thomas L.
Corley, Douglas A.
Cook, Michael B.
Casson, Alan G.
Kamangar, Farin
Abnet, Christian C.
Risch, Harvey A.
Giffen, Carol
Freedman, Neal D.
Chow, Wong-Ho
Sadeghi, Shahram
Pandeya, Nirmala
Whiteman, David C.
Murray, Liam J.
Bernstein, Leslie
Gammon, Marilie D.
Wu, Anna H.
TI Nonsteroidal Anti-inflammatory Drug Use Reduces Risk of Adenocarcinomas
of the Esophagus and Esophagogastric Junction in a Pooled Analysis
SO GASTROENTEROLOGY
LA English
DT Article
DE BEACON; Esophageal Neoplasm; Stomach Cancer; Anti-Inflammatory Agent
ID SELECTIVE CYCLOOXYGENASE-2 INHIBITION; BARRETTS-ESOPHAGUS;
GASTRIC-CANCER; INCREASED EXPRESSION; RANDOMIZED-TRIAL; UNITED-STATES;
ASPIRIN; METAANALYSIS; CHEMOPREVENTION; PREVENTION
AB BACKGROUND & AIMS: Regular use of aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) has been reported to reduce risks of esophageal adenocarcinoma (EAC) and esophagogastric junctional adenocarcinoma (EGJA). However, individual studies have been too small to accurately assess the effects of medication type, frequency, or duration of use. We performed a pooled analysis to investigate these associations. METHODS: We performed a pooled analysis of 6 population-based studies within the Barrett's and Esophageal Adenocarcinoma Consortium to evaluate the association between NSAID use and the risk of EAC and EGJA, using uniform exposure definitions. We collected information from 6 studies (5 case-control and 1 cohort), with a total of 1226 EAC and 1140 EGJA cases, on aspirin and/or NSAID use. Study-specific odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using multivariate adjusted logistic regression models and then pooled using a random effects meta-analysis model. RESULTS: Compared with nonusers, individuals who have used NSAIDs had a statistically significant reduced risk of EAC (OR, 0.68; 95% CI, 0.56-0.83); they also appeared to have a reduced risk of EGJA (OR, 0.83; 95% CI, 0.66-1.03). Similar reductions in risk were observed among individuals who took aspirin or nonaspirin NSAIDs. The highest levels of frequency (daily or more frequently) and duration (>= 10 years) of NSAID use were associated with an approximately 40% reduction in risk of EAC, with ORs of 0.56 (95% CI, 0.43-0.73; P-trend < .001) and 0.63 (95% CI, 0.45-0.90; P-trend = .04), respectively. CONCLUSIONS: Although reverse causation could, in part, explain the inverse association observed between NSAID use and EAC risk, our pooled analysis suggests a possible role for NSAIDs in prevention of adenocarcinomas of the esophagus and esophagogastric junction.
C1 [Liao, Linda M.] NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20852 USA.
[Vaughan, Thomas L.] Fred Hutchinson Canc Res Ctr, Program Epidemiol, Seattle, WA 98104 USA.
[Corley, Douglas A.] Kaiser Permanente, Div Res, Oakland, CA USA.
[Corley, Douglas A.] Kaiser Permanente, Oakland Med Ctr, Oakland, CA USA.
[Casson, Alan G.] Univ Saskatchewan, Dept Surg, Saskatoon, SK, Canada.
[Kamangar, Farin] Morgan State Univ, Sch Community Hlth & Policy, Dept Publ Anal, Baltimore, MD 21239 USA.
[Risch, Harvey A.] Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06510 USA.
[Giffen, Carol] Informat Management Serv Inc, Silver Spring, MD USA.
[Sadeghi, Shahram; Pandeya, Nirmala; Whiteman, David C.] Queensland Inst Med Res, Div Genet & Populat Hlth, Brisbane, Qld 4006, Australia.
[Murray, Liam J.] Queens Univ, Ctr Publ Hlth, Belfast, Antrim, North Ireland.
[Bernstein, Leslie] City Hope Natl Med Ctr, Beckman Res Inst, Div Canc Etiol, Dept Populat Sci, Duarte, CA USA.
[Gammon, Marilie D.] Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC USA.
[Wu, Anna H.] USC Norris Comprehens Canc Ctr, Keck Sch Med, Dept Prevent Med, Los Angeles, CA USA.
RP Liao, LM (reprint author), NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd,EPS Room 8003, Rockville, MD 20852 USA.
EM liaolm@mail.nih.gov
RI Liao, Linda/B-3960-2011; Cook, Michael/A-5641-2009; Abnet,
Christian/C-4111-2015; Freedman, Neal/B-9741-2015; Whiteman,
David/P-2728-2014; Pandeya, Nirmala/F-8054-2010
OI Cook, Michael/0000-0002-0533-7302; Abnet, Christian/0000-0002-3008-7843;
Freedman, Neal/0000-0003-0074-1098; Whiteman, David/0000-0003-2563-9559;
Liao, Linda/0000-0002-1923-5294; Pandeya, Nirmala/0000-0003-1462-4968
FU National Institutes of Health (NIH); California Tobacco-Related Research
Program [3RT-0122, 10RT-0251]; National Cancer Institute [CA59636]; Nova
Scotia Health Research Foundation [N419]; Ireland-Northern Ireland
Co-operation Research Project; Northern Ireland Research and Development
Office; Health Research Board, Ireland; Queensland Cancer Fund; National
Health and Medical Research Council of Australia [199600];
[U01-CA57949]; [U01-CA57983]; [U01-CA57923]
FX Supported in part by the Intramural Program of the National Institutes
of Health (NIH). The US Multicenter Study was funded by U01-CA57949 (to
T. L. V.), U01-CA57983 (to M. D. G.), and U01-CA57923 (to H. A. R). The
Los Angeles County Multi-ethnic Study was funded by 3RT-0122 ("Smoking
and Risk of Proximal Vs. Distal Gastric Cancer," to A. H. W.) and
10RT-0251 ("Smoking, microsatellite instability & gastric cancers," to
A. H. W.) from the California Tobacco-Related Research Program and
CA59636 (to L. B.) from the National Cancer Institute. The Nova Scotia
Barrett Esophagus Study was supported by the Nova Scotia Health Research
Foundation ("Molecular mechanisms and lifestyle risk factor interactions
in the pathogenesis of human esophageal adenocarcinoma," N419, to A. G.
C.). The Factors Influencing the Barrett's Adenocarcinoma Relationship
Study was funded by an Ireland-Northern Ireland Co-operation Research
Project Grant sponsored by the Northern Ireland Research and Development
Office, and the Health Research Board, Ireland (All-Ireland case-control
study of Oesophageal Adenocarcinoma and Barrett's Oesophagus, to L.J.M.
and Harry Comber). The Australian Study of Esophageal Cancer was
supported by the Queensland Cancer Fund and the National Health and
Medical Research Council of Australia (program no. 199600, to D. C. W.,
Adele C. Green, Nicholas K. Hayward, Peter G. Parsons, David M. Purdie,
and Penelope M. Webb). The NIH-AARP Diet and Health Study was funded by
the Intramural Program of the NIH.
NR 45
TC 48
Z9 50
U1 0
U2 15
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
J9 GASTROENTEROLOGY
JI Gastroenterology
PD MAR
PY 2012
VL 142
IS 3
BP 442
EP U85
DI 10.1053/j.gastro.2011.11.019
PG 16
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 898XC
UT WOS:000300774700022
PM 22108196
ER
PT J
AU Woo, DH
Kim, SK
Lim, HJ
Heo, J
Park, HS
Kang, GY
Kim, SE
You, HJ
Hoeppner, DJ
Kim, Y
Kwon, H
Choi, TH
Lee, JH
Hong, SH
Song, KW
Ahn, EK
Chenoweth, JG
Tesar, PJ
McKay, RDG
Kim, JH
AF Woo, Dong-Hun
Kim, Suel-Kee
Lim, Hee-Joung
Heo, Jeonghoon
Park, Hyung Soon
Kang, Gum-Yong
Kim, Sung-Eun
You, Hyun-Ju
Hoeppner, Daniel J.
Kim, Youngchul
Kwon, Heechung
Choi, Tae Hyun
Lee, Joo Hee
Hong, Su Hee
Song, Kang Won
Ahn, Eun-Kyung
Chenoweth, Josh G.
Tesar, Paul J.
McKay, Ronald D. G.
Kim, Jong-Hoon
TI Direct and Indirect Contribution of Human Embryonic Stem Cell-Derived
Hepatocyte-Like Cells to Liver Repair in Mice
SO GASTROENTEROLOGY
LA English
DT Article
DE hES Cells; Hepatitis; Mouse Model; Stem Cell Therapy
ID IN-VITRO; ANIMAL-MODELS; REGENERATION; DIFFERENTIATION; INJURY;
EXPRESSION; MECHANISM; TRANSPLANTATION; NEOVASCULARIZATION; FIBROSIS
AB BACKGROUND & AIMS: Many studies of embryonic stem cells have investigated direct cell replacement of damaged tissues, but little is known about how donor cell-derived signals affect host tissue regeneration. We investigated the direct and indirect roles of human embryonic stem cell-derived cells in liver repair in mice. METHODS: To promote the initial differentiation of human embryonic stem cells into mesendoderm, we activated the beta-catenin signaling pathway with lithium; cells were then further differentiated into hepatocyte-like cells. The differentiated cells were purified by indocyanine green staining and laser microdissection and characterized by immunostaining, polymerase chain reaction, biochemical function, electron microscopy, and transplantation analyses. To investigate indirect effects of these cells, secreted proteins (secretomes) were analyzed by a label-free quantitative mass spectrometry. Carbon tetrachloride was used to induce acute liver injury in mice; cells or secreted proteins were administered by intrasplenic or intraperitoneal injection, respectively. RESULTS: The differentiated hepatocyte-like cells had multiple features of normal hepatocytes, engrafted efficiently into mice, and continued to have hepatic features; they promoted proliferation of host hepatocytes and revascularization of injured host liver tissues. Proteomic analysis identified proteins secreted from these cells that might promote host tissue repair. Injection of the secreted proteins into injured livers of mice promoted significant amounts of tissue regeneration without cell grafts. CONCLUSIONS: Hepatocyte-like cells derived from human embryonic stem cells contribute to recovery of injured liver tissues in mice, not only by cell replacement but also by delivering trophic factors that support endogenous liver regeneration.
C1 [Woo, Dong-Hun; Kim, Suel-Kee; Lim, Hee-Joung; Kim, Sung-Eun; You, Hyun-Ju; Kim, Jong-Hoon] Korea Univ, Coll Life Sci & Biotechnol, Div Biotechnol, Lab Stem Cell Biol, Seoul 136713, South Korea.
[Kim, Youngchul] Korea Univ, Coll Med, Dept Surg, Seoul 136713, South Korea.
[Kim, Suel-Kee; Hoeppner, Daniel J.; Chenoweth, Josh G.; Tesar, Paul J.; McKay, Ronald D. G.] Natl Inst Neurol Disorders & Stroke, Mol Biol Lab, NIH, Bethesda, MD USA.
[Heo, Jeonghoon; Ahn, Eun-Kyung] Kosin Univ, Coll Med, Dept Mol Biol & Immunol, Pusan, South Korea.
[Park, Hyung Soon; Kang, Gum-Yong] Diatech Korea Co Ltd, Seoul, South Korea.
[Kwon, Heechung; Lee, Joo Hee] Korea Inst Radiol & Med Sci, Div Radiat Canc Res, Seoul, South Korea.
[Choi, Tae Hyun; Hong, Su Hee] Korea Inst Radiol & Med Sci, Radiopharmaceut & Lab Nucl Med, Seoul, South Korea.
[Song, Kang Won] Natl Canc Ctr, Dept Pathol, Gyeonggi Do, South Korea.
RP Kim, JH (reprint author), Korea Univ, Coll Life Sci & Biotechnol, Div Biotechnol, Lab Stem Cell Biol, West Bldg,Room 304,Sci Campus,1 Anam Dong 5 Ga, Seoul 136713, South Korea.
EM jhkim@korea.ac.kr
RI Kim, Jong-Hoon/F-2504-2013; Tesar, Paul/C-9848-2014; Kim,
Jong-Hoon/H-1476-2015
OI Tesar, Paul/0000-0003-1532-3155;
FU Stem Cell Research Center [SC-3130]; Korea Research Foundation
[KRF-313-2008-2-C00737]; Ministry of Education, Science and Technology,
Republic of Korea
FX Supported by a grant (SC-3130) from Stem Cell Research Center of the
21st Century Frontier Research Program and a grant
(KRF-313-2008-2-C00737) from the Korea Research Foundation funded by the
Ministry of Education, Science and Technology, Republic of Korea.
NR 47
TC 48
Z9 54
U1 2
U2 15
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
J9 GASTROENTEROLOGY
JI Gastroenterology
PD MAR
PY 2012
VL 142
IS 3
BP 602
EP 611
DI 10.1053/j.gastro.2011.11.030
PG 10
WC Gastroenterology & Hepatology
SC Gastroenterology & Hepatology
GA 898XC
UT WOS:000300774700039
PM 22138358
ER
PT J
AU Belal, C
Ameli, NJ
El Kommos, A
Bezalel, S
Al'Khafaji, AM
Mughal, MR
Mattson, MP
Kyriazis, GA
Tyrberg, B
Chan, SL
AF Belal, Cherine
Ameli, Neema J.
El Kommos, Adam
Bezalel, Spencer
Al'Khafaji, Aziz M.
Mughal, Mohamed R.
Mattson, Mark P.
Kyriazis, George A.
Tyrberg, Bjoern
Chan, Sic L.
TI The homocysteine-inducible endoplasmic reticulum (ER) stress protein
Herp counteracts mutant -synuclein-induced ER stress via the homeostatic
regulation of ER-resident calcium release channel proteins
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID ALPHA-SYNUCLEIN; PARKINSONS-DISEASE; DOPAMINERGIC-NEURONS; RYANODINE
RECEPTOR; SUBSTANTIA-NIGRA; CORTICAL-NEURONS; NEUROTOXIN MODEL;
DEGRADATION; APOPTOSIS; DEATH
AB Endoplasmic reticulum (ER) stress has been implicated as an initiator or contributing factor in neurodegenerative diseases. The mechanisms that lead to ER stress and whereby ER stress contributes to the degenerative cascades remain unclear but their understanding is critical to devising effective therapies. Here we show that knockdown of Herp (Homocysteine-inducible ER stress protein), an ER stress-inducible protein with an ubiquitin-like (UBL) domain, aggravates ER stress-mediated cell death induced by mutant -synuclein (Syn) that causes an inherited form of Parkinsons disease (PD). Functionally, Herp plays a role in maintaining ER homeostasis by facilitating proteasome-mediated degradation of ER-resident Ca-2 release channels. Deletion of the UBL domain or pharmacological inhibition of proteasomes abolishes the Herp-mediated stabilization of ER Ca-2 homeostasis. Furthermore, knockdown or pharmacological inhibition of ER Ca-2 release channels ameliorates ER stress, suggesting that impaired homeostatic regulation of Ca-2 channels promotes a protracted ER stress with the consequent activation of ER stress-associated apoptotic pathways. Interestingly, sustained upregulation of ER stress markers and aberrant accumulation of ER Ca-2 release channels were detected in transgenic mutant A53T-Syn mice. Collectively, these data establish a causative link between impaired ER Ca-2 homeostasis and chronic ER stress in the degenerative cascades induced by mutant Syn and suggest that Herp is essential for the resolution of ER stress through maintenance of ER Ca-2 homeostasis. Our findings suggest a therapeutic potential in PD for agents that increase Herp levels or its ER Ca-2-stabilizing action.
C1 [Belal, Cherine; Ameli, Neema J.; El Kommos, Adam; Bezalel, Spencer; Al'Khafaji, Aziz M.; Chan, Sic L.] Univ Cent Florida, Burnett Sch Biomed Sci, Coll Med, Orlando, FL 32816 USA.
[Mughal, Mohamed R.; Mattson, Mark P.] NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA.
[Kyriazis, George A.; Tyrberg, Bjoern] Sanford Burnham Med Res Inst, Diabet & Obes Res Ctr, Orlando, FL USA.
RP Chan, SL (reprint author), 4000 Cent Florida Blvd, Orlando, FL 32816 USA.
EM schan@mail.ucf.edu
RI Mattson, Mark/F-6038-2012
FU American Federation on Aging Research; National Institutes of Health
(NIH) [1R21NS066265-01]; National Institute on Aging of the National
Institute of Health
FX This work was supported by the American Federation on Aging Research (to
S. L. C.); National Institutes of Health (NIH 1R21NS066265-01 to S. L.
C.); and the National Institute on Aging Intramural Research Program of
the National Institute of Health (to M.P.M.).
NR 43
TC 20
Z9 22
U1 0
U2 6
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0964-6906
J9 HUM MOL GENET
JI Hum. Mol. Genet.
PD MAR 1
PY 2012
VL 21
IS 5
BP 963
EP 977
DI 10.1093/hmg/ddr502
PG 15
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 891UL
UT WOS:000300242000001
PM 22045699
ER
PT J
AU Sterky, FH
Hoffman, AF
Milenkovic, D
Bao, B
Paganelli, A
Edgar, D
Wibom, R
Lupica, CR
Olson, L
Larsson, NG
AF Sterky, Fredrik H.
Hoffman, Alexander F.
Milenkovic, Dusanka
Bao, Betty
Paganelli, Arianna
Edgar, Daniel
Wibom, Rolf
Lupica, Carl R.
Olson, Lars
Larsson, Nils-Goeran
TI Altered dopamine metabolism and increased vulnerability to MPTP in mice
with partial deficiency of mitochondrial complex I in dopamine neurons
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID PARKINSONS-DISEASE; SUBSTANTIA-NIGRA; DNA DELETIONS; PARS COMPACTA;
HUMAN BRAIN; CHAIN; MODEL; MOUSE; TRANSPORT; TOXICITY
AB A variety of observations support the hypothesis that deficiency of complex I [reduced nicotinamide-adenine dinucleotide (NADH):ubiquinone oxidoreductase] of the mitochondrial respiratory chain plays a role in the pathophysiology of Parkinsons disease (PD). However, recent data from a study using mice with knockout of the complex I subunit NADH:ubiquinone oxidoreductase iron-sulfur protein 4 (Ndufs4) has challenged this concept as these mice show degeneration of non-dopamine neurons. In addition, primary dopamine (DA) neurons derived from such mice, reported to lack complex I activity, remain sensitive to toxins believed to act through inhibition of complex I. We tissue-specifically disrupted the Ndufs4 gene in mouse heart and found an apparent severe deficiency of complex I activity in disrupted mitochondria, whereas oxidation of substrates that result in entry of electrons at the level of complex I was only mildly reduced in intact isolated heart mitochondria. Further analyses of detergent-solubilized mitochondria showed the mutant complex I to be unstable but capable of forming supercomplexes with complex I enzyme activity. The loss of Ndufs4 thus causes only a mild complex I deficiency in vivo. We proceeded to disrupt Ndufs4 in midbrain DA neurons and found no overt neurodegeneration, no loss of striatal innervation and no symptoms of Parkinsonism in tissue-specific knockout animals. However, DA homeostasis was abnormal with impaired DA release and increased levels of DA metabolites. Furthermore, Ndufs4 DA neuron knockouts were more vulnerable to the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Taken together, these findings lend in vivo support to the hypothesis that complex I deficiency can contribute to the pathophysiology of PD.
C1 [Milenkovic, Dusanka; Larsson, Nils-Goeran] Max Planck Inst Biol Ageing, D-50931 Cologne, Germany.
[Sterky, Fredrik H.; Paganelli, Arianna; Edgar, Daniel; Wibom, Rolf; Larsson, Nils-Goeran] Karolinska Inst, Dept Lab Med, SE-17177 Stockholm, Sweden.
[Sterky, Fredrik H.; Olson, Lars] Karolinska Inst, Dept Neurosci, SE-17177 Stockholm, Sweden.
[Hoffman, Alexander F.; Bao, Betty; Lupica, Carl R.] NIDA, Electrophysiol Res Sect, Baltimore, MD 21224 USA.
RP Larsson, NG (reprint author), Max Planck Inst Biol Ageing, Robert Koch Str 21, D-50931 Cologne, Germany.
EM larsson@age.mpg.de
RI Hoffman, Alexander/H-3035-2012
OI Hoffman, Alexander/0000-0002-2676-0628
FU National Institutes of Health-Karolinska Institute; Swedish Research
Council [K2011-62X-21870-01-6, K2009-61X-03185-39-3]; Swedish Brain
Power; Parkinson Foundation; Karolinska Institutet; US Public Health
Service, National Institute on Drug Abuse
FX This work was supported by the National Institutes of Health-Karolinska
Institute Graduate Partnership Program for the Neurosciences (F. H. S.),
The Swedish Research Council (grant numbers K2011-62X-21870-01-6,
K2009-61X-03185-39-3), Swedish Brain Power, The Parkinson Foundation,
The Karolinska Institutet and US Public Health Service, National
Institute on Drug Abuse, Intramural Research Program.
NR 41
TC 35
Z9 38
U1 1
U2 9
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0964-6906
J9 HUM MOL GENET
JI Hum. Mol. Genet.
PD MAR 1
PY 2012
VL 21
IS 5
BP 1078
EP 1089
DI 10.1093/hmg/ddr537
PG 12
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 891UL
UT WOS:000300242000010
PM 22090423
ER
PT J
AU Han, SS
Yeager, M
Moore, LE
Wei, MH
Pfeiffer, R
Toure, O
Purdue, MP
Johansson, M
Scelo, G
Chung, CC
Gaborieau, V
Zaridze, D
Schwartz, K
Szeszenia-Dabrowska, N
Davis, F
Bencko, V
Colt, JS
Janout, V
Matveev, V
Foretova, L
Mates, D
Navratilova, M
Boffetta, P
Berg, CD
Grubb, RL
Stevens, VL
Thun, MJ
Diver, WR
Gapstur, SM
Albanes, D
Weinstein, SJ
Virtamo, J
Burdett, L
Brisuda, A
McKay, JD
Fraumeni, JF
Chatterjee, N
Rosenberg, PS
Rothman, N
Brennan, P
Chow, WH
Tucker, MA
Chanock, SJ
Toro, JR
AF Han, Summer S.
Yeager, Meredith
Moore, Lee E.
Wei, Ming-Hui
Pfeiffer, Ruth
Toure, Ousmane
Purdue, Mark P.
Johansson, Mattias
Scelo, Ghislaine
Chung, Charles C.
Gaborieau, Valerie
Zaridze, David
Schwartz, Kendra
Szeszenia-Dabrowska, Neonilia
Davis, Faith
Bencko, Vladimir
Colt, Joanne S.
Janout, Vladimir
Matveev, Vsevolod
Foretova, Lenka
Mates, Dana
Navratilova, M.
Boffetta, Paolo
Berg, Christine D.
Grubb, Robert L., III
Stevens, Victoria L.
Thun, Michael J.
Diver, W. Ryan
Gapstur, Susan M.
Albanes, Demetrius
Weinstein, Stephanie J.
Virtamo, Jarmo
Burdett, Laurie
Brisuda, Antonin
McKay, James D.
Fraumeni, Joseph F., Jr.
Chatterjee, Nilanjan
Rosenberg, Philip S.
Rothman, Nathaniel
Brennan, Paul
Chow, Wong-Ho
Tucker, Margaret A.
Chanock, Stephen J.
Toro, Jorge R.
TI The chromosome 2p21 region harbors a complex genetic architecture for
association with risk for renal cell carcinoma
SO HUMAN MOLECULAR GENETICS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; KIDNEY CANCER; FAMILY-HISTORY; MUTATIONS;
SEQUENCES; RESOURCE; OBESITY; DESIGN; COMMON; TRIAL
AB In follow-up of a recent genome-wide association study (GWAS) that identified a locus in chromosome 2p21 associated with risk for renal cell carcinoma (RCC), we conducted a fine mapping analysis of a 120 kb region that includes EPAS1. We genotyped 59 tagged common single-nucleotide polymorphisms (SNPs) in 2278 RCC and 3719 controls of European background and observed a novel signal for rs9679290 [P 5.75 10(8), per-allele odds ratio (OR) 1.27, 95 confidence interval (CI): 1.171.39]. Imputation of common SNPs surrounding rs9679290 using HapMap 3 and 1000 Genomes data yielded two additional signals, rs4953346 (P 4.09 10(14)) and rs12617313 (P 7.48 10(12)), both highly correlated with rs9679290 (r(2) 0.95), but interestingly not correlated with the two SNPs reported in the GWAS: rs11894252 and rs7579899 (r(2) 0.1 with rs9679290). Genotype analysis of rs12617313 confirmed an association with RCC risk (P 1.72 10(9), per-allele OR 1.28, 95 CI: 1.181.39) In conclusion, we report that chromosome 2p21 harbors a complex genetic architecture for common RCC risk variants.
C1 [Han, Summer S.; Yeager, Meredith; Moore, Lee E.; Wei, Ming-Hui; Pfeiffer, Ruth; Toure, Ousmane; Purdue, Mark P.; Chung, Charles C.; Colt, Joanne S.; Albanes, Demetrius; Weinstein, Stephanie J.; Burdett, Laurie; Fraumeni, Joseph F., Jr.; Chatterjee, Nilanjan; Rosenberg, Philip S.; Rothman, Nathaniel; Chow, Wong-Ho; Tucker, Margaret A.; Chanock, Stephen J.; Toro, Jorge R.] NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA.
[Berg, Christine D.] NCI, Canc Prevent Div, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA.
[Yeager, Meredith] NCI, Core Genotyping Facil, Adv Technol Ctr, NIH,SAIC Frederick Inc, Frederick, MD 21701 USA.
[Johansson, Mattias; Scelo, Ghislaine; Gaborieau, Valerie; McKay, James D.; Brennan, Paul] IARC, Lyon, France.
[Zaridze, David; Matveev, Vsevolod] NN Blokhin Canc Res Ctr, Moscow, Russia.
[Schwartz, Kendra] Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA.
[Zaridze, David] Wayne State Univ, Dept Family Med, Detroit, MI USA.
[Szeszenia-Dabrowska, Neonilia] Inst Occupat Med, Dept Epidemiol, Lodz, Poland.
[Davis, Faith] Univ Illinois, Sch Publ Hlth, Div Epidemiol & Biostat, Chicago, IL USA.
[Bencko, Vladimir] Charles Univ Prague, Fac Med 1, Inst Hyg & Epidemiol, Prague, Czech Republic.
[Janout, Vladimir] Palacky Univ, CR-77147 Olomouc, Czech Republic.
[Foretova, Lenka; Navratilova, M.] Masaryk Mem Canc Inst, Dept Canc Epidemiol & Genet, Brno, Czech Republic.
[Mates, Dana] Inst Publ Hlth, Bucharest, Romania.
[Boffetta, Paolo] Mt Sinai Sch Med, Tisch Canc Inst, New York, NY USA.
[Grubb, Robert L., III] Washington Univ, Sch Med, Div Urol Surg, St Louis, MO 63110 USA.
[Stevens, Victoria L.; Thun, Michael J.; Diver, W. Ryan; Gapstur, Susan M.] Amer Canc Soc, Epidemiol Res Program, Atlanta, GA 30329 USA.
[Virtamo, Jarmo] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland.
[Brisuda, Antonin] Univ Hosp Motol, Dept Urol, Prague, Czech Republic.
[Toro, Jorge R.] DC VAMC, Washington, DC USA.
RP Toro, JR (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Execut Plaza S,Room 7012, Rockville, MD 20892 USA.
EM toroj@mail.nih.gov
RI Zaridze, David/K-5605-2013; Berg , Christine/K-1047-2014; Janout,
Vladimir/M-5133-2014; Tucker, Margaret/B-4297-2015; Albanes,
Demetrius/B-9749-2015; Szeszenia-Dabrowska, Neonila/F-7190-2010; Purdue,
Mark/C-9228-2016;
OI Purdue, Mark/0000-0003-1177-3108; mates, dana/0000-0002-6219-9807
FU Division of Cancer Epidemiology and Genetics; National Cancer Institute;
NIH; DHHS; Bethesda, MD, USA; European Commission [IC15-CT96-0313]
FX This research was supported in part by the Intramural Research Program
of the Division of Cancer Epidemiology and Genetics, National Cancer
Institute, NIH, DHHS, Bethesda, MD, USA, and by European Commission
INCOCOPERNICUS grant IC15-CT96-0313.
NR 44
TC 15
Z9 16
U1 0
U2 5
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0964-6906
J9 HUM MOL GENET
JI Hum. Mol. Genet.
PD MAR 1
PY 2012
VL 21
IS 5
BP 1190
EP 1200
DI 10.1093/hmg/ddr551
PG 11
WC Biochemistry & Molecular Biology; Genetics & Heredity
SC Biochemistry & Molecular Biology; Genetics & Heredity
GA 891UL
UT WOS:000300242000020
PM 22113997
ER
PT J
AU Bower, M
Salomon, R
Allanson, J
Antignac, C
Benedicenti, F
Benetti, E
Binenbaum, G
Jensen, UB
Cochat, P
DeCramer, S
Dixon, J
Drouin, R
Falk, MJ
Feret, H
Gise, R
Hunter, A
Johnson, K
Kumar, R
Lavocat, MP
Martin, L
Moriniere, V
Mowat, D
Murer, L
Nguyen, HT
Peretz-Amit, G
Pierce, E
Place, E
Rodig, N
Salerno, A
Sastry, S
Sato, T
Sayer, JA
Schaafsma, GCP
Shoemaker, L
Stockton, DW
Tan, WH
Tenconi, R
Vanhille, P
Vats, A
Wang, XJ
Warman, B
Weleber, RG
White, SM
Wilson-Brackett, C
Zand, DJ
Eccles, M
Schimmenti, LA
Heidet, L
AF Bower, Matthew
Salomon, Remi
Allanson, Judith
Antignac, Corinne
Benedicenti, Francesco
Benetti, Elisa
Binenbaum, Gil
Jensen, Uffe B.
Cochat, Pierre
DeCramer, Stephane
Dixon, Joanne
Drouin, Regen
Falk, Marni J.
Feret, Holly
Gise, Robert
Hunter, Alasdair
Johnson, Kisha
Kumar, Rajiv
Lavocat, Marie Pierre
Martin, Laura
Moriniere, Vincent
Mowat, David
Murer, Luisa
Nguyen, Hiep T.
Peretz-Amit, Gabriela
Pierce, Eric
Place, Emily
Rodig, Nancy
Salerno, Ann
Sastry, Sujatha
Sato, Tadashi
Sayer, John A.
Schaafsma, Gerard C. P.
Shoemaker, Lawrence
Stockton, David W.
Tan, Wen-Hann
Tenconi, Romano
Vanhille, Philippe
Vats, Abhay
Wang, Xinjing
Warman, Berta
Weleber, Richard G.
White, Susan M.
Wilson-Brackett, Carolyn
Zand, Dina J.
Eccles, Michael
Schimmenti, Lisa A.
Heidet, Laurence
TI Update of PAX2 mutations in renal coloboma syndrome and establishment of
a locus-specific database
SO HUMAN MUTATION
LA English
DT Article
DE PAX2; renal coloboma syndrome; papillorenal syndrome
ID URETERAL BUD APOPTOSIS; MORNING GLORY SYNDROME; MISSENSE MUTATION;
VARIABLE PHENOTYPE; GENE MUTATION; MUTANT MICE; FAMILY; DISEASE; KIDNEY;
HYPOPLASIA
AB Renal coloboma syndrome, also known as papillorenal syndrome is an autosomal-dominant disorder characterized by ocular and renal malformations. Mutations in the paired-box gene, PAX2, have been identified in approximately half of individuals with classic findings of renal hypoplasia/dysplasia and abnormalities of the optic nerve. Prior to 2011, there was no actively maintained locus-specific database (LSDB) cataloguing the extent of genetic variation in the PAX2 gene and phenotypic variation in individuals with renal coloboma syndrome. Review of published cases and the collective diagnostic experience of three laboratories in the United States, France, and New Zealand identified 55 unique mutations in 173 individuals from 86 families. The three clinical laboratories participating in this collaboration contributed 28 novel variations in 68 individuals in 33 families, which represent a 50% increase in the number of variations, patients, and families published in the medical literature. An LSDB was created using the Leiden Open Variation Database platform: www.lovd.nl/PAX2. The most common findings reported in this series were abnormal renal structure or function (92% of individuals), ophthalmological abnormalities (77% of individuals), and hearing loss (7% of individuals). Additional clinical findings and genetic counseling implications are discussed. Hum Mutat 33:457466, 2012. (C) 2011 Wiley Periodicals, Inc.
C1 [Bower, Matthew] Univ Minnesota Med Ctr, Div Genet & Metab, Minneapolis, MN USA.
[Salomon, Remi; Antignac, Corinne] Hop Necker Enfants Malad, INSERM, U983, Paris, France.
[Salomon, Remi; Moriniere, Vincent; Heidet, Laurence] APHP, Ctr Reference Malad Renales Hereditaires Enfant &, Paris, France.
[Salomon, Remi; Heidet, Laurence] Hop Necker Enfants Malad, APHP, Serv Nephrol Pediat, Paris, France.
[Allanson, Judith; Hunter, Alasdair] Childrens Hosp Eastern Ontario, Dept Genet, Ottawa, ON K1H 8L1, Canada.
[Allanson, Judith; Hunter, Alasdair] Univ Ottawa, Ottawa, ON, Canada.
[Antignac, Corinne; Moriniere, Vincent] Hop Necker Enfants Malad, APHP, Dept Genet, Paris, France.
[Salomon, Remi; Antignac, Corinne] Univ Paris 05, Paris, France.
[Benedicenti, Francesco] Reg Hosp Bolzano, Dept Pediat, Genet Counseling Serv S Tyrol, Bolzano, Italy.
[Benetti, Elisa; Murer, Luisa] Univ Padua, Nephrol Dialysis & Transplant Unit, Padua, Italy.
[Murer, Luisa; Tenconi, Romano] Univ Padua, Dept Pediat, Padua, Italy.
[Binenbaum, Gil; Pierce, Eric] Childrens Hosp Philadelphia, Dept Ophthalmol, Philadelphia, PA 19104 USA.
[Falk, Marni J.; Feret, Holly; Pierce, Eric; Place, Emily] Childrens Hosp Philadelphia, Dept Pediat, Philadelphia, PA 19104 USA.
[Falk, Marni J.; Feret, Holly; Place, Emily] Childrens Hosp Philadelphia, Div Human Genet, Philadelphia, PA 19104 USA.
[Jensen, Uffe B.] Aarhus Univ Hosp, Dept Clin Genet, DK-8000 Aarhus, Denmark.
[Cochat, Pierre] Hosp Civils Lyon, Ctr Reference Malad Renales Rares, Lyon, France.
[DeCramer, Stephane] CHU Toulouse, Hop Enfants, Serv Nephrol Med Interne Hypertens Pediat, F-31059 Toulouse, France.
[DeCramer, Stephane] Fac Med Toulouse, INSERM, Inst Cardiovasc & Metab Dis, U1048, F-31073 Toulouse, France.
[Dixon, Joanne] Wellington Hosp, Cent & So Reg Genet Serv, Wellington, New Zealand.
[Drouin, Regen] Univ Sherbrooke, Div Genet, Dept Pediat, Sherbrooke, PQ J1K 2R1, Canada.
[Gise, Robert] UMASS Mem Childrens Med Ctr, Dept Ophthalmol, Worcester, MA USA.
[Salerno, Ann] UMASS Mem Childrens Med Ctr, Dept Pediat, Worcester, MA USA.
[Johnson, Kisha] Rush Univ Med Ctr, Dept Pediat, Chicago, IL USA.
[Kumar, Rajiv] Auckland City Hosp, Reg Blood & Canc Serv, Auckland, New Zealand.
[Lavocat, Marie Pierre] CHU St Etienne, Hop Nord, Dept Paediat, St Etienne, France.
[Martin, Laura] Nemours Childrens Clin, Div Genet, Jacksonville, FL USA.
[Mowat, David] Sydney Childrens Hosp, Dept Med Genet, Sydney, NSW, Australia.
[Nguyen, Hiep T.] Childrens Hosp Boston, Dept Urol, Boston, MA USA.
[Rodig, Nancy] Childrens Hosp Boston, Div Nephrol, Boston, MA USA.
[Tan, Wen-Hann] Childrens Hosp Boston, Div Genet, Boston, MA USA.
[Peretz-Amit, Gabriela] Rabin Med Ctr, Dept Med Genet, Petah Tiqwa, Israel.
[Sastry, Sujatha; Stockton, David W.] Childrens Hosp Michigan, Div Genet & Metab Disorders, Detroit, MI 48201 USA.
[Sato, Tadashi] Saga Med Sch, Dept Pediat, Saga, Japan.
[Sayer, John A.] Newcastle Univ, Int Ctr Life, Inst Med Genet, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England.
[Schaafsma, Gerard C. P.] Leiden Univ Med Ctr, Dept Human Genet, Leiden, Netherlands.
[Shoemaker, Lawrence] Univ Louisville, Div Pediat Nephrol, Louisville, KY 40292 USA.
[Stockton, David W.] Wayne State Sch Med, Div Genet & Metab Disorders, Detroit, MI USA.
[Vanhille, Philippe] Ctr Hosp Valenciennes, Serv Nephrol & Med Interne, Valenciennes, France.
[Vats, Abhay] Univ Pittsburgh, Dept Pediat, Div Pediat Nephrol, Pittsburgh, PA 15260 USA.
[Wang, Xinjing] NEI, NIH, Bethesda, MD 20892 USA.
[Warman, Berta] Newborn Screening Program, Minneapolis, MN USA.
[Weleber, Richard G.] Oregon Hlth & Sci Univ, Casey Eye Inst, Dept Ophthalmol & Mol & Med Genet, Portland, OR 97201 USA.
[White, Susan M.] Royal Childrens Hosp, Genet Hlth Serv Victoria, Parkville, Vic 3052, Australia.
[White, Susan M.] Royal Childrens Hosp, Murdoch Childrens Res Inst, Parkville, Vic 3052, Australia.
[Wilson-Brackett, Carolyn] Fullerton Genet Ctr, Dept Genet, Asheville, NC USA.
[Zand, Dina J.] Childrens Natl Med Ctr, Div Genet & Metab, Washington, DC 20010 USA.
[Eccles, Michael] Univ Otago, Dunedin Sch Med, Dev Genet Grp, Dunedin, New Zealand.
[Schimmenti, Lisa A.] Univ Minnesota, Inst Human Genet, Ctr Dev Biol, Dept Pediat, Minneapolis, MN 55455 USA.
[Schimmenti, Lisa A.] Univ Minnesota, Inst Human Genet, Ctr Dev Biol, Dept Ophthalmol, Minneapolis, MN 55455 USA.
[Schimmenti, Lisa A.] Univ Minnesota, Inst Human Genet, Ctr Dev Biol, Dept Genet Cell Biol & Dev, Minneapolis, MN 55455 USA.
RP Bower, M (reprint author), Univ Minnesota Med Ctr, Div Genet & Metab, 420 Delaware St SE,MMC 485, Minneapolis, MN USA.
EM mbower1@fairview.org
RI Falk, Marni/K-1997-2014; Schaafsma, Gerard/F-6138-2014
OI Sayer, John/0000-0003-1881-3782; Kumar, Rajiv/0000-0002-6093-0395;
Murer, Luisa/0000-0002-3010-2337; Schaafsma, Gerard/0000-0001-6351-7486
FU European Community's Seventh Framework Programme [FP7/2007-2013];
GEN2PHEN [200754]
FX The authors would like to thank the patients and families who have
contributed to this work. In addition, the authors wish to thank the
many professionals who are not formally recognized, but have made
significant contributions to this work including the staff of the
molecular diagnostics laboratory at the University of Minnesota Medical
Center, Fairview. Construction of the LOVD database has received funding
from the European Community's Seventh Framework Programme
(FP7/2007-2013) under grant agreement number 200754: The GEN2PHEN
project.
NR 61
TC 27
Z9 28
U1 1
U2 6
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1059-7794
J9 HUM MUTAT
JI Hum. Mutat.
PD MAR
PY 2012
VL 33
IS 3
BP 457
EP 466
DI 10.1002/humu.22020
PG 10
WC Genetics & Heredity
SC Genetics & Heredity
GA 898AB
UT WOS:000300706000003
PM 22213154
ER
PT J
AU Kanaan, Z
Rai, SN
Eichenberger, MR
Barnes, C
Dworkin, AM
Weller, C
Cohen, E
Roberts, H
Keskey, B
Petras, RE
Crawford, NPS
Galandiuk, S
AF Kanaan, Ziad
Rai, Shesh N.
Eichenberger, M. Robert
Barnes, Christopher
Dworkin, Amy M.
Weller, Clayton
Cohen, Eric
Roberts, Henry
Keskey, Bobby
Petras, Robert E.
Crawford, Nigel P. S.
Galandiuk, Susan
TI Differential MicroRNA expression tracks neoplastic progression in
inflammatory bowel disease-associated colorectal cancer
SO HUMAN MUTATION
LA English
DT Article
DE IBD; Crohn disease; ulcerative colitis; cancer; dysplasia; microRNA
ID ULCERATIVE-COLITIS; CROHNS-DISEASE; COLON-CANCER; SAMPLE-SIZE;
DNA-CONTENT; P53; RISK; DYSPLASIA; EPIDEMIOLOGY; SUPPRESSOR
AB One of the most serious complications faced by patients with inflammatory bowel disease (IBD) is the potential development of colorectal cancer (CRC). There is a compelling need to enhance the accuracy of cancer screening of IBD patients. MicroRNAs (miRNAs) are small nonprotein-coding RNAs that play important roles in CRC oncogenesis. In this study, we report differential miRNA expression in IBD patients with associated CRC from non-neoplastic tissue to dysplasia and eventually cancer. In addition, we identify and examine the role of dysregulated miRNAs in the TP53 pathway. In our CD patients, six miRNAs were upregulated from non-neoplastic tissue to dysplasia, but downregulated from dysplasia to cancer (miR-122, miR-181a, miR-146b-5p, let-7e, miR-17, miR-143) (P < 0.001). Six differentially expressed miRNAs affected the TP53 pathway (miR-122, miR-214, miR-372, miR-15b, let-7e, miR-17) (P < 0.001). Using two human colon cancer cell lines (HT-29 and HCT-116), E2F1, an upstream regulator of TP53, was downregulated in both cell lines transfected with let-7e (P < 0.05) as well as in HCT-116 cells transfected with miR-17 (P < 0.05). Additionally, cyclin G, a cell-cycle regulator miR-122 target was downregulated in both cell lines (P < 0.05). Unique differentially expressed miRNAs were observed in CD-associated CRC progression. Six of these miRNAs had a tumorigenic effect on the TP53 pathway; the effect of three of which was studied using cell lines. Hum Mutat 33:551560, 2012. (C) 2012 Wiley Periodicals, Inc.
C1 [Kanaan, Ziad; Eichenberger, M. Robert; Weller, Clayton; Cohen, Eric; Roberts, Henry; Keskey, Bobby; Galandiuk, Susan] Univ Louisville, Sch Med, Dept Surg, Price Inst Surg Res, Louisville, KY 40292 USA.
[Kanaan, Ziad; Eichenberger, M. Robert; Weller, Clayton; Cohen, Eric; Roberts, Henry; Keskey, Bobby; Galandiuk, Susan] Univ Louisville, Sch Med, Sect Colorectal Surg, Louisville, KY 40292 USA.
[Rai, Shesh N.; Barnes, Christopher] Univ Louisville, Sch Publ Hlth & Informat Sci, Dept Bioinformat & Biostat, Louisville, KY 40292 USA.
[Dworkin, Amy M.; Crawford, Nigel P. S.] NHGRI, NIH, Bethesda, MD 20892 USA.
[Petras, Robert E.] Ameripath, Oakwood Village, OH USA.
RP Galandiuk, S (reprint author), Univ Louisville, Sch Med, Dept Surg, Price Inst Surg Res, Louisville, KY 40292 USA.
EM s0gala01@louisville.edu
OI Kanaan, Ziad/0000-0001-5376-562X
FU Center for Environmental Genomics and Integrative Biology (CEGIB)
[1P30ES014443-01A1]; Wendell Cherry Chair-James Graham Brown Cancer
Center, University of Louisville
FX This publication is made possible in part by the John W. and Caroline
Price Family Trust, a gift from Ms. Sara Shallenberger Brown, and
NIH/NIEHS grant 1P30ES014443-01A1) to The Center for Environmental
Genomics and Integrative Biology (CEGIB). Dr. Shesh Rai was partly
supported by the Wendell Cherry Chair-James Graham Brown Cancer Center,
University of Louisville.
NR 42
TC 47
Z9 48
U1 0
U2 8
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1059-7794
J9 HUM MUTAT
JI Hum. Mutat.
PD MAR
PY 2012
VL 33
IS 3
BP 551
EP 560
DI 10.1002/humu.22021
PG 10
WC Genetics & Heredity
SC Genetics & Heredity
GA 898AB
UT WOS:000300706000016
PM 22241525
ER
PT J
AU Sayres, MAW
Brookes, AJ
Chanock, SJ
Cheung, VG
Goldstein, DB
Jin, L
Kwok, PY
AF Sayres, Melissa A. Wilson
Brookes, Anthony J.
Chanock, Stephen J.
Cheung, Vivian G.
Goldstein, David B.
Jin, Li
Kwok, Pui-Yan
TI HGV2011: Personalized genomic medicine meets the incidentalome
SO HUMAN MUTATION
LA English
DT Editorial Material
DE human variation; GWAS; SNP; medical genomics
AB The 12th International Meeting on Human Genome Variation and Complex Genome Analysis (HGV2011: Berkeley, California, USA, 8th10th September 2011) was a stimulating workshop where researchers from academia and industry explored the latest progress, challenges, and opportunities in genome variation research. Key themes included progress beyond GWAS, variation in human populations, use of sequence data in medical settings, large-scale sequencing data analysis, and bioinformatics approaches to large datasets. Hum Mutat 33:582585, 2012. (C) 2011 Wiley Periodicals, Inc.
C1 [Sayres, Melissa A. Wilson] Univ Calif Berkeley, Dept Stat, Berkeley, CA 94720 USA.
[Sayres, Melissa A. Wilson] Univ Calif Berkeley, Dept Integrat Biol, Berkeley, CA 94720 USA.
[Brookes, Anthony J.] Univ Leicester, Dept Genet, Leicester LE1 7RH, Leics, England.
[Chanock, Stephen J.] NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA.
[Chanock, Stephen J.] NCI, Ctr Canc Res, Bethesda, MD 20892 USA.
[Cheung, Vivian G.] Univ Penn, Howard Hughes Med Inst, Philadelphia, PA 19104 USA.
[Goldstein, David B.] Hosp Sick Children, Res Inst, Ctr Appl Genom, Program Genet & Genom Biol, Toronto, ON M5G 1X8, Canada.
[Jin, Li] Fudan Univ, State Key Lab Genet Engn, Shanghai 200433, Peoples R China.
[Jin, Li] Fudan Univ, MOE Key Lab Contemporary Anthropol, Sch Life Sci, Shanghai 200433, Peoples R China.
[Jin, Li] Fudan Univ, Inst Biomed Sci, Shanghai 200433, Peoples R China.
[Kwok, Pui-Yan] Univ Calif San Francisco, Dept Dermatol, Cardiovasc Res Inst, San Francisco, CA 94143 USA.
[Kwok, Pui-Yan] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA.
RP Sayres, MAW (reprint author), 1005 VLSB,MC 3140, Berkeley, CA 94720 USA.
EM mwilsonsayres@berkeley.edu; Pui.Kwok@ucsf.edu
RI Kwok, Pui-Yan/F-7725-2014; Jin, Li/C-1468-2009;
OI Kwok, Pui-Yan/0000-0002-5087-3059; Jin, Li/0000-0002-4546-2415; Wilson
Sayres, Melissa/0000-0002-2614-0285
FU National Human Genome Research Institute (NHGRI) [R13 HG003953]; The
National Cancer Institute (NCI); The McLaughlin Centre at the University
of Toronto; Gen2Phen
FX National Human Genome Research Institute (NHGRI, R13 HG003953); The
National Cancer Institute (NCI); The McLaughlin Centre at the University
of Toronto; Gen2Phen.
NR 0
TC 1
Z9 1
U1 0
U2 2
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 1059-7794
EI 1098-1004
J9 HUM MUTAT
JI Hum. Mutat.
PD MAR
PY 2012
VL 33
IS 3
BP 582
EP 585
DI 10.1002/humu.22008
PG 4
WC Genetics & Heredity
SC Genetics & Heredity
GA 898AB
UT WOS:000300706000019
ER
PT J
AU Leach, RE
Jessmon, P
Coutifaris, C
Kruger, M
Myers, ER
Ali-Fehmi, R
Carson, S
Legro, RS
Schlaff, WD
Carr, BR
Steinkampf, MP
Silva, S
Leppert, PC
Giudice, L
Diamond, MP
Armant, DR
AF Leach, Richard E.
Jessmon, Philip
Coutifaris, Christos
Kruger, Michael
Myers, Evan R.
Ali-Fehmi, Rouba
Carson, SandraA.
Legro, Richard S.
Schlaff, William D.
Carr, Bruce R.
Steinkampf, Michael P.
Silva, Susan
Leppert, Phyllis C.
Giudice, Linda
Diamond, Michael P.
Armant, D. Randall
CA Reproductive Med Network
TI High throughput, cell type-specific analysis of key proteins in human
endometrial biopsies of women from fertile and infertile couples
SO HUMAN REPRODUCTION
LA English
DT Article
DE endometrium; idiopathic infertility; protein expression; developmental
regulation; immunohistochemistry
ID LEUKEMIA INHIBITORY FACTOR; GENE-EXPRESSION PROFILES;
PROGESTERONE-RECEPTOR-B; DNA MICROARRAY ANALYSIS; GROWTH-FACTOR;
MENSTRUAL-CYCLE; GLYCODELIN-A; IMPLANTATION FAILURE; BLASTOCYST
IMPLANTATION; UNEXPLAINED INFERTILITY
AB Although histological dating of endometrial biopsies provides little help for prediction or diagnosis of infertility, analysis of individual endometrial proteins, proteomic profiling and transcriptome analysis have suggested several biomarkers with altered expression arising from intrinsic abnormalities, inadequate stimulation by or in response to gonadal steroids or altered function due to systemic disorders. The objective of this study was to delineate the developmental dynamics of potentially important proteins in the secretory phase of the menstrual cycle, utilizing a collection of endometrial biopsies from women of fertile (n 89) and infertile (n 89) couples.
Progesterone receptor-B (PGR-B), leukemia inhibitory factor, glycodelin/progestagen-associated endometrial protein (PAEP), homeobox A10, heparin-binding EGF-like growth factor, calcitonin and chemokine ligand 14 (CXCL14) were measured using a high-throughput, quantitative immunohistochemical method. Significant cyclic and tissue-specific regulation was documented for each protein, as well as their dysregulation in women of infertile couples. Infertile patients demonstrated a delay early in the secretory phase in the decline of PGR-B (P 0.05) and premature mid-secretory increases in PAEP (P 0.05) and CXCL14 (P 0.05), suggesting that the implantation interval could be closing early. Correlation analysis identified potential interactions among certain proteins that were disrupted by infertility.
This approach overcomes the limitations of a small sample number. Protein expression and localization provided important insights into the potential roles of these proteins in normal and pathological development of the endometrium that is not attainable from transcriptome analysis, establishing a basis for biomarker, diagnostic and targeted drug development for women with infertility.
C1 [Jessmon, Philip; Kruger, Michael; Ali-Fehmi, Rouba; Diamond, Michael P.; Armant, D. Randall] Wayne State Univ, CS Mott Ctr Human Growth & Dev, Sch Med, Detroit, MI 48201 USA.
[Leach, Richard E.] Michigan State Univ, Spectrum Hlth Med Grp, Grand Rapids, MI USA.
[Jessmon, Philip; Armant, D. Randall] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Reprod & Adult Endocrinol, Bethesda, MD USA.
[Coutifaris, Christos] Univ Penn, Sch Med, Philadelphia, PA 19104 USA.
[Silva, Susan] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC USA.
[Carson, SandraA.] Brown Univ, Providence, RI 02912 USA.
[Legro, Richard S.] Penn State Univ, Hershey, PA USA.
[Schlaff, William D.] Univ Colorado, Denver, CO 80202 USA.
[Carr, Bruce R.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA.
[Steinkampf, Michael P.] Univ Alabama, Birmingham, AL USA.
[Giudice, Linda] Univ Calif San Francisco, San Francisco, CA 94143 USA.
RP Armant, DR (reprint author), Wayne State Univ, CS Mott Ctr Human Growth & Dev, Sch Med, 275 E Hancock Ave, Detroit, MI 48201 USA.
EM d.armant@wayne.edu
OI Diamond, Michael/0000-0001-6353-4489; Armant, D.
Randall/0000-0001-5904-9325
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development (NICHD), NIH [U54HD40093, HD040093]; NICHD National
Cooperative Reproductive Medicine Network [HD045966, HD27049, HD38997,
HD39005, HD27011, HD33172, HD38988, HD38992, HD38998]; NICHD, NIH, DHHS
FX This work was supported by the Eunice Kennedy Shriver National Institute
of Child Health and Human Development (NICHD), NIH through Cooperative
Agreement (U54HD40093) as part of the Specialized Cooperative Center
Program in Reproduction and Infertility Research to R. E. L., grants to
R. E. L. (HD040093) and D. R. A. (HD045966), grants from the NICHD
National Cooperative Reproductive Medicine Network to C. C. (HD27049),
E. R. M. (HD38997), M. P. D. (HD39005), S. A. C. (HD27011), M. P. S.
(HD33172), B. R. C. (HD38988), R. S. L. (HD38992) and W. D. S. (HD38998)
and the Intramural Research Program of the NICHD, NIH, DHHS (D.R.A.).
NR 105
TC 17
Z9 18
U1 1
U2 4
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0268-1161
J9 HUM REPROD
JI Hum. Reprod.
PD MAR
PY 2012
VL 27
IS 3
BP 814
EP 828
DI 10.1093/humrep/der436
PG 15
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 895QA
UT WOS:000300510100024
PM 22215622
ER
PT J
AU Bairagi, S
Gopal, J
Nathan, AA
Babu, SS
Kumar, NP
Dixit, M
AF Bairagi, Soumi
Gopal, Jayashree
Nathan, Abel A.
Babu, Subash S.
Kumar, N. Pavan
Dixit, Madhulika
TI Glucose-induced increase in circulating progenitor cells is blunted in
polycystic amenorrhoeic subjects
SO HUMAN REPRODUCTION
LA English
DT Article
DE amenorrhea; polycystic ovaries; bone marrow-derived stem cells; insulin
resistance; OGTT
ID OVARY-SYNDROME; BONE-MARROW; PERIPHERAL-BLOOD; STEM-CELLS;
INSULIN-RESISTANCE; CARDIOVASCULAR RISK; METABOLIC SYNDROME; HUMAN
ENDOMETRIUM; MENSTRUAL-CYCLE; EXPRESSION
AB Glucose-induced kinetics of bone marrow-derived stem cells in healthy females is presently unknown. The objectives of this study were to determine whether circulating levels of CD133, CD34 and CD133CD34 cells increase in response to glucose load in healthy females and whether the kinetics is altered in amenorrhoeic women. The other objective of the work was to compare the endothelial differentiation potential of peripheral blood-derived endothelial progenitor cells(EPCs) from healthy versus amenorrhoeic women.
In this casecontrol study, 44 amenorrhoeic subjects and 36 age-matched females with no menstrual disturbance were recruited at Apollo Hospitals, a Tertiary health care center in Chennai, India. Circulating bone marrow-derived stem cells were measured by two color direct flow cytometry. Cultured progenitor cells were characterized at Day 7 and 14 for expression of endothelial markers and production of nitric oxide (NO) via immunofluoroscence.
The amenorrhoeic subjects were insulin resistant with homeostatic model of assessment of insulin resistance values of 3.33 0.3 versus 1.75 0.148 observed for controls (P 0.0001). Among the amenorrhoeic subjects, 38 subjects had polycystic ovaries with no signs of hyperandrogenism. Fasting levels of CD133, CD34 and CD133CD34 cells were reduced in amenorrhoeic subjects (P 0.001). There was a 1.5 to 2-fold increase in the circulating levels of these cells in response to 75 g oral glucose challenge at 1 and 2 h post-load conditions in controls, which was significantly blunted for CD133 (P 0.001) and CD133CD34 (P 0.001) cells in amenorrhoeic subjects. A positive correlation was observed between estrogen and fasting CD133 (r 0.205, P 0.070), CD34 (r 0.249, P 0.027) and CD133CD34 (r 0.217, P 0.055) cell counts. Additionally, fasting counts for CD34 and CD133CD34 cells positively correlated with FSH and inversely correlated with LH and C-peptide in the polycystic group. Cultured cells from polycystic subjects exhibited reduced adherence to fibronectin and expressed lower levels of endothelial nitric-oxide synthase and NO.
Oral glucose-induced increase in circulating numbers of CD133 and CD133CD34 cells and endothelial differentiation potential of peripheral blood-derived EPCs is attenuated in insulin resistant amenorrhoeic subjects.
C1 [Bairagi, Soumi; Nathan, Abel A.; Dixit, Madhulika] IIT Madras, Lab Vasc Biol, Dept Biotechnol, Madras 600036, Tamil Nadu, India.
[Gopal, Jayashree] Apollo Hosp, Dept Diabetol, Madras 600006, Tamil Nadu, India.
[Babu, Subash S.; Kumar, N. Pavan] Natl Inst Hlth Int Ctr Excellence Res, Madras 600031, Tamil Nadu, India.
[Babu, Subash S.; Kumar, N. Pavan] NCI, SAIC Frederick Inc, Frederick, MD 21702 USA.
RP Dixit, M (reprint author), IIT Madras, Lab Vasc Biol, Dept Biotechnol, BT 415, Madras 600036, Tamil Nadu, India.
EM mdixit@iitm.ac.in
FU Council of Scientific and Industrial Research (CSIR), Govt. of India;
Department of Biotechnology (DBT), Govt. of India; Apollo Hospitals
Education and Research Foundation (AHERF), India
FX Ms Soumi Bairagi acknowledges Council of Scientific and Industrial
Research (CSIR), Govt. of India for Senior Research Fellowship and Dr
Madhulika Dixit acknowledges Department of Biotechnology (DBT), Govt. of
India for Innovative Young Biotechnologist Award fellowship. Help
rendered by Spectra team of AHERF is also acknowledged.; This work was
funded by Apollo Hospitals Education and Research Foundation (AHERF),
India.
NR 55
TC 1
Z9 1
U1 0
U2 1
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0268-1161
J9 HUM REPROD
JI Hum. Reprod.
PD MAR
PY 2012
VL 27
IS 3
BP 844
EP 853
DI 10.1093/humrep/der457
PG 10
WC Obstetrics & Gynecology; Reproductive Biology
SC Obstetrics & Gynecology; Reproductive Biology
GA 895QA
UT WOS:000300510100026
PM 22252083
ER
PT J
AU Akinbami, LJ
Sullivan, SD
Campbell, JD
Grundmeier, RW
Hartert, TV
Lee, TA
Smith, RA
AF Akinbami, Lara J.
Sullivan, Sean D.
Campbell, Jonathan D.
Grundmeier, Robert W.
Hartert, Tina V.
Lee, Todd A.
Smith, Robert A.
TI Asthma outcomes: Healthcare utilization and costs
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Article
DE Asthma hospital admissions; asthma emergency department visits; asthma
outpatient visits; asthma medication use; asthma intervention resource
use; asthma study perspective
ID INNER-CITY CHILDREN; QUALITY-OF-CARE; TO-TREAT ASTHMA; ACTIVITY
IMPAIRMENT; WORK PRODUCTIVITY; CHILDHOOD ASTHMA; TIME; INTERVENTION;
MOTION; IMPACT
AB Background: Measures of healthcare utilization and indirect impact of asthma morbidity are used to assess clinical interventions and estimate cost.
Objective: National Institutes of Health institutes and other federal agencies convened an expert group to propose standardized measurement, collection, analysis, and reporting of healthcare utilization and cost outcomes in future asthma studies.
Methods: We used comprehensive literature reviews and expert opinion to compile a list of asthma healthcare utilization outcomes that we classified as core (required in future studies), supplemental (used according to study aims and standardized), and emerging (requiring validation and standardization). We also have identified methodology to assign cost to these outcomes. This work was discussed at an National Institutes of Health-organized workshop in March 2010 and finalized in September 2011.
Results: We identified 3 ways to promote comparability across clinical trials for measures of healthcare utilization, resource use, and cost: (1) specify the study perspective (patient, clinician, payer, and society); (2) standardize the measurement period (ideally 12 months); and (3) use standard units to measure healthcare utilization and other asthma-related events.
Conclusions: Large clinical trials and observational studies should collect and report detailed information on healthcare utilization, intervention resources, and indirect impact of asthma, so that costs can be calculated and cost-effectiveness analyses can be conducted across several studies. Additional research is needed to develop standard, validated survey instruments for collection of provider-reported and participant-reported data regarding asthma-related health care. (J Allergy Clin Immunol 2012; 129: S49-64.)
C1 [Smith, Robert A.] NHLBI, DLD, NIH, Bethesda, MD 20892 USA.
[Akinbami, Lara J.] Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Hyattsville, MD 20782 USA.
[Sullivan, Sean D.] Univ Washington, Seattle, WA 98195 USA.
[Campbell, Jonathan D.] Univ Colorado, Aurora, CO USA.
[Grundmeier, Robert W.] Childrens Hosp Philadelphia, Philadelphia, PA USA.
[Hartert, Tina V.] Vanderbilt Univ, Med Ctr, Nashville, TN USA.
[Lee, Todd A.] Univ Illinois, Chicago, IL USA.
RP Smith, RA (reprint author), NHLBI, DLD, NIH, 6701 Rockledge Dr, Bethesda, MD 20892 USA.
EM smithra3@nhlbi.nih.gov
RI Campbell, Jonathan/C-1279-2015
FU National Institute of Allergy and Infectious Diseases; National Heart,
Lung, and Blood Institute; Eunice Kennedy Shriver National Institute of
Child Health and Human Development; National Institute of Environmental
Health Sciences; Agency for Healthcare Research and Quality; Merck
Childhood Asthma Network; Robert Wood Johnson Foundation; US
Environmental Protection Agency; Merck; AHRQ; NIH; MCHB
FX The Asthma Outcomes work shop was funded by contributions from the
National Institute of Allergy and Infectious Diseases; the National
Heart, Lung, and Blood Institute; the Eunice Kennedy Shriver National
Institute of Child Health and Human Development; the National Institute
of Environmental Health Sciences; the Agency for Healthcare Research and
Quality; and the Merck Childhood Asthma Network, as well as by a grant
from the Robert Wood Johnson Foundation. Contributions from the National
Heart, Lung, and Blood Institute; the National Institute of Allergy and
Infectious Diseases; the Eunice Kennedy Shriver National Institute of
Child Health and Human Development; the National Institute of
Environmental Health Sciences; and the US Environmental Protection
Agency funded the publication of this article and all other articles in
this supplement.; Disclosure of potential conflict of interest: S. D.
Sullivan has received research support from Merck. J. D. Campbell is a
consultant for VeriTech Corp and has received research support from the
Agency for Healthcare Research and Quality. R. W. Grundmeier has
received research support from AHRQ, the NIH, and MCHB. T. V. Hartert
has received research support from the NIH and AHRQ; is an Associate
Editor for the ATS; and is a consultant for Merck. The rest of the
authors declare that they have no relevant conflicts of interest.
NR 67
TC 33
Z9 33
U1 2
U2 8
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD MAR
PY 2012
VL 129
IS 3
SU S
BP S49
EP S64
DI 10.1016/j.jaci.2011.12.984
PG 16
WC Allergy; Immunology
SC Allergy; Immunology
GA 901OL
UT WOS:000300976600005
PM 22386509
ER
PT J
AU Busse, WW
Morgan, WJ
Taggart, V
Togias, A
AF Busse, William W.
Morgan, Wayne J.
Taggart, Virginia
Togias, Alkis
TI Asthma outcomes workshop: Overview
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Article
DE Asthma clinical research; National Institutes of Health asthma
initiatives; standardizing outcomes
AB Background: Asthma clinical research will highly benefit from standardization of major outcomes in terms of definition and assessment methodology. This will permit useful comparisons across interventional or observational studies and will allow more effective data sharing.
Objective: National Institutes of Health (NIH) institutes and the Agency for Healthcare Research and Quality convened a workshop involving 7 expert subcommittees to propose which asthma outcomes should be assessed with standardized methodology in future asthma clinical research studies.
Methods: Each subcommittee utilized comprehensive literature reviews and expert opinion to compile a list of asthma outcomes and classified them as either core (required in future studies), supplemental (to be used according to study aims and standardized), or emerging (requiring validation and standardization). This work was discussed at an NIH-organized workshop in March 2010 and finalized in September 2011.
Results: Outcomes for study participant characterization, as well as for prospective clinical trial intervention and observational studies, were proposed for adults and children, and methodologies for outcome collection and reporting were determined. Furthermore, the workshop identified areas in which new outcomes or instruments for their measurement need to be developed and validated.
Conclusions: Standardized outcomes for clinical research in asthma have been proposed. Participating NIH institutes and other federal agencies will consider these recommendations in future clinical research initiatives in asthma. (J Allergy Clin Immunol 2012; 129: S1-8.)
C1 [Togias, Alkis] NIAID, DAIT, NIH, Bethesda, MD 20892 USA.
[Busse, William W.] Univ Wisconsin, Madison, WI 53706 USA.
[Morgan, Wayne J.] Univ Arizona, Phoenix, AZ USA.
[Taggart, Virginia] NHLBI, Bethesda, MD 20892 USA.
RP Togias, A (reprint author), NIAID, DAIT, NIH, 6610 Rockledge Dr, Bethesda, MD 20892 USA.
EM togiasa@niaid.nih.gov
FU National Institute of Allergy and Infectious Diseases; National Heart,
Lung, and Blood Institute; Eunice Kennedy Shriver National Institute of
Child Health and Human Development; National Institute of Environmental
Health Sciences; Agency for Healthcare Research and Quality; Merck
Childhood Asthma Network; Robert Wood Johnson Foundation; US
Environmental Protection Agency; National Institutes of Health (NIAID);
National Institutes of Health (NHLBI); NIH-NHLBI CARE Network; Cystic
Fibrosis Network
FX The Asthma Outcomes workshop was funded by contributions from the
National Institute of Allergy and Infectious Diseases; the National
Heart, Lung, and Blood Institute; the Eunice Kennedy Shriver National
Institute of Child Health and Human Development; the National Institute
of Environmental Health Sciences; the Agency for Healthcare Research and
Quality; and the Merck Childhood Asthma Network, as well as by a grant
from the Robert Wood Johnson Foundation. Contributions from the National
Heart, Lung, and Blood Institute; the National Institute of Allergy and
Infectious Diseases; the Eunice Kennedy Shriver National Institute of
Child Health and Human Development; the National Institute of
Environmental Health Sciences; and the US Environmental Protection
Agency funded the publication of this article and all other articles in
this supplement.; Disclosure of potential conflict of interest: W. W.
Busse is on the Advisory Board for Centocor and Merck; is a consultant
for Amgen, AstraZeneca, Novartis, GlaxoSmithKline, MedImmune, Genentech,
and Boehringer Ingelheim; is on the Actelion Date Safety Monitoring
Board; and has received research support from the National Institutes of
Health (NIAID and NHLBI). W. J. Morgan is a consultant for Genentech,
Novartis, and the Cystic Fibrosis Foundation; has received research
support from the NIH-NHLBI CARE Network and the Cystic Fibrosis Network;
and is a speaker for Phadia. The rest of the authors declare that they
have no relevant conflicts of interest.
NR 3
TC 47
Z9 47
U1 0
U2 4
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD MAR
PY 2012
VL 129
IS 3
SU S
BP S1
EP S8
DI 10.1016/j.jaci.2011.12.985
PG 8
WC Allergy; Immunology
SC Allergy; Immunology
GA 901OL
UT WOS:000300976600001
PM 22386504
ER
PT J
AU Cloutier, MM
Schatz, M
Castro, M
Clark, N
Kelly, HW
Mangione-Smith, R
Sheller, J
Sorkness, C
Stoloff, S
Gergen, P
AF Cloutier, Michelle M.
Schatz, Michael
Castro, Mario
Clark, Noreen
Kelly, H. William
Mangione-Smith, Rita
Sheller, James
Sorkness, Christine
Stoloff, Stuart
Gergen, Peter
TI Asthma outcomes: Composite scores of asthma control
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Article
DE Asthma Control Questionnaire; Asthma Control Test; Asthma Therapy
Assessment Questionnaire; Childhood Asthma Control Test
ID QUALITY-OF-LIFE; HEALTH-CARE UTILIZATION; PATIENT-REPORTED OUTCOMES;
EXHALED NITRIC-OXIDE; CONTROL QUESTIONNAIRE; SPANISH VERSION; REAL-LIFE;
UNCONTROLLED DISEASE; ADULT ASTHMATICS; CLINICAL SCORES
AB Background: Current asthma guidelines recommend assessing the level of a patient's asthma control. Consequently, there is increasing use of asthma control as an outcome measure in clinical research studies. Several composite assessment instruments have been developed to measure asthma control.
Objective: National Institutes of Health institutes and federal agencies convened an expert group to propose the most appropriate standardized composite score of asthma control instruments to be used in future asthma studies.
Methods: We conducted a comprehensive search of PubMed using both the National Library of Medicine's Medical Subject Headings and key terms to identify studies that attempted to develop and/or test composite score instruments for asthma control. We classified instruments as core (required in future studies), supplemental (used according to study aims and standardized), or emerging (requiring validation and standardization). This work was discussed at a National Institutes of Health-organized workshop convened in March 2010 and finalized in September 2011.
Results: We identified 17 composite score instruments with published validation information; all had comparable content. Eight instruments demonstrated responsiveness over time; 3 demonstrated responsiveness to treatment. A minimal clinically important difference has been established for 3 instruments. The instruments have demographic limitations; some are proprietary, and their use could be limited by cost.
Conclusion: Two asthma composite score instruments are sufficiently validated for use in adult populations, but additional research is necessary to validate their use in nonwhite populations. Gaps also exist in validating instruments for pediatric populations. (J Allergy Clin Immunol 2012; 129: S24-33.)
C1 [Gergen, Peter] NIAID, DAIT, NIH, Bethesda, MD 20892 USA.
[Cloutier, Michelle M.] Univ Connecticut, Farmington, CT USA.
[Castro, Mario] Washington Univ, St Louis, MO 63130 USA.
[Schatz, Michael] Kaiser Permanente, San Diego, CA USA.
[Clark, Noreen] Univ Michigan, Ann Arbor, MI 48109 USA.
[Kelly, H. William] Univ New Mexico, Albuquerque, NM 87131 USA.
[Mangione-Smith, Rita] Univ Washington, Seattle, WA 98195 USA.
[Sheller, James] Vanderbilt Univ, Nashville, TN USA.
[Sorkness, Christine] Univ Wisconsin, Madison, WI 53706 USA.
RP Gergen, P (reprint author), NIAID, DAIT, NIH, 6610 Rockledge Dr, Bethesda, MD 20892 USA.
EM pgergen@niaid.nih.gov
FU National Institute of Allergy and Infectious Diseases; National Heart,
Lung, and Blood Institute; Eunice Kennedy Shriver National Institute of
Child Health and Human Development; National Institute of Environmental
Health Sciences; Agency for Healthcare Research and Quality; Merck
Childhood Asthma Network; Robert Wood Johnson Foundation; US
Environmental Protection Agency; Aerocrine; GlaxoSmithKline; Merck;
Genentech; Asthmatx; Elsevier; Amgen; Ception/Cephalon; MedImmune;
Novartis; NIH; Actelion Pharmaceuticals
FX The Asthma Outcomes workshop was funded by contributions from the
National Institute of Allergy and Infectious Diseases; the National
Heart, Lung, and Blood Institute; the Eunice Kennedy Shriver National
Institute of Child Health and Human Development; the National Institute
of Environmental Health Sciences; the Agency for Healthcare Research and
Quality; and the Merck Childhood Asthma Network, as well as by a grant
from the Robert Wood Johnson Foundation. Contributions from the National
Heart, Lung, and Blood Institute; the National Institute of Allergy and
Infectious Diseases; the Eunice Kennedy Shriver National Institute of
Child Health and Human Development; the National Institute of
Environmental Health Sciences, and the US Environmental Protection
Agency funded the publication of this article and all other articles in
this supplement.; Disclosure of potential conflict of interest: M.
Schatz has consulted for Amgen and has received research support from
Aerocrine, GlaxoSmithKline, Merck, and Genentech. M. Castro has received
consulting and speaker fees from Asthmatx; is a speaker and is on the
advisory board for Genentech; is a speaker for AstraZeneca, Merck, and
GlaxoSmithKline; has received royalties from Elsevier; and has received
research support from Asthmatx, Amgen, Ception/Cephalon, Genentech,
MedImmune, Merck, Novartis, the NIH, and GlaxoSmithKline. J. R. Sheller
has received research support from Actelion Pharmaceuticals. S. W.
Stoloff is Chairman of the Allergy and Asthma Network Mothers of
Asthmatics Board. The rest of the authors declare that they have no
relevant conflicts of interest.
NR 89
TC 72
Z9 73
U1 1
U2 10
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD MAR
PY 2012
VL 129
IS 3
SU S
BP S24
EP S33
DI 10.1016/j.jaci.2011.12.980
PG 10
WC Allergy; Immunology
SC Allergy; Immunology
GA 901OL
UT WOS:000300976600003
PM 22386507
ER
PT J
AU Fuhlbrigge, A
Peden, D
Apter, AJ
Boushey, HA
Camargo, CA
Gern, J
Heymann, PW
Martinez, FD
Mauger, D
Teague, WG
Blaisdell, C
AF Fuhlbrigge, Anne
Peden, David
Apter, Andrea J.
Boushey, Homer A.
Camargo, Carlos A., Jr.
Gern, James
Heymann, Peter W.
Martinez, Fernando D.
Mauger, David
Teague, William G.
Blaisdell, Carol
TI Asthma outcomes: Exacerbations
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Article
DE Asthma exacerbations; severity of acute asthma; systemic steroids in
asthma; urgent asthma care
ID RANDOMIZED CONTROLLED-TRIAL; METERED-DOSE INHALER; MILD PERSISTENT
ASTHMA; EXHALED NITRIC-OXIDE; INNER-CITY CHILDREN; BUDESONIDE/FORMOTEROL
COMBINATION THERAPY; POORLY CONTROLLED ASTHMA; BROMIDE PLUS FENOTEROL;
AMBIENT AIR-POLLUTION; DRY POWDER INHALER
AB Background: The goals of asthma treatment include preventing recurrent exacerbations. Yet there is no consensus about the terminology for describing or defining "exacerbation" or about how to characterize an episode's severity.
Objective: National Institutes of Health institutes and other federal agencies convened an expert group to propose how asthma exacerbation should be assessed as a standardized asthma outcome in future asthma clinical research studies.
Methods: We used comprehensive literature reviews and expert opinion to compile a list of asthma exacerbation outcomes and classified them as either core (required in future studies), supplemental (used according to study aims and standardized), or emerging (requiring validation and standardization). This work was discussed at a National Institutes of Health-organized workshop in March 2010 and finalized in September 2011.
Results: No dominant definition of "exacerbation" was found. The most widely used definitions included 3 components, all related to treatment, rather than symptoms: (1) systemic use of corticosteroids, (2) asthma-specific emergency department visits or hospitalizations, and (3) use of short-acting beta-agonists as quick-relief (sometimes referred to as "rescue" or "reliever") medications.
Conclusions: The working group participants propose that the definition of "asthma exacerbation" be "a worsening of asthma requiring the use of systemic corticosteroids to prevent a serious outcome." As core outcomes, they propose inclusion and separate reporting of several essential variables of an exacerbation. Furthermore, they propose the development of a standardized, component-based definition of "exacerbation" with clear thresholds of severity for each component. (J Allergy Clin Immunol 2012; 129: S34-48.)
C1 [Blaisdell, Carol] NHLBI, DLD, NIH, Bethesda, MD 20892 USA.
[Fuhlbrigge, Anne] Brigham & Womens Hosp, Boston, MA 02115 USA.
[Peden, David] Univ N Carolina, Chapel Hill, NC USA.
[Apter, Andrea J.] Univ Penn, Philadelphia, PA 19104 USA.
[Boushey, Homer A.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Camargo, Carlos A., Jr.] Massachusetts Gen Hosp, Boston, MA 02114 USA.
[Gern, James] Univ Wisconsin, Madison, WI 53706 USA.
[Heymann, Peter W.; Teague, William G.] Univ Virginia, Charlottesville, VA USA.
[Martinez, Fernando D.] Univ Arizona, Tucson, AZ USA.
[Mauger, David] Penn State Univ, Hershey, PA USA.
RP Blaisdell, C (reprint author), NHLBI, DLD, NIH, 6701 Rockledge Dr, Bethesda, MD 20892 USA.
EM blaisdellcj@nhlbi.nih.gov
FU National Institute of Allergy and Infectious Diseases; National Heart,
Lung, and Blood Institute; Eunice Kennedy Shriver National Institute of
Child Health and Human Development; National Institute of Environmental
Health Sciences; Agency for Healthcare Research and Quality; Merck
Childhood Asthma Network; Robert Wood Johnson Foundation; US
Environmental Protection Agency; NIH/NIAID; MedImmune; Aquinox
Pharmaceuticals; GlaxoSmithKline; Genentech; Sanofi-Aventis; Centocor;
Boehringer Ingelheim; Biota; Theraclone; NIH; Novartis; NIH/NHLBI;
American Lung Association
FX The Asthma Outcomes workshop was funded by contributions from the
National Institute of Allergy and Infectious Diseases; the National
Heart, Lung, and Blood Institute; the Eunice Kennedy Shriver National
Institute of Child Health and Human Development; the National Institute
of Environmental Health Sciences; the Agency for Healthcare Research and
Quality; and the Merck Childhood Asthma Network, as well as by a grant
from the Robert Wood Johnson Foundation. Contributions from the National
Heart, Lung, and Blood Institute; the National Institute of Allergy and
Infectious Diseases; the Eunice Kennedy Shriver National Institute of
Child Health and Human Development; the National Institute of
Environmental Health Sciences; and the US Environmental Protection
Agency funded the publication of this article and all other articles in
this supplement.; Disclosure of potential conflict of interest: A.
Fuhlbrigge is on the Merck Respiratory Advisory Board and is a
consultant for the Lovelace Respiratory and Research Institute. D. Peden
has received research support from the NIH/NIAID, MedImmune, the US
Environmental Protection Agency, and Aquinox Pharmaceuticals. A. J.
Apter has received research support from the NHLBI and is on the AAAAI
Board of Directors. H. A. Boushey has provided ad-hoc consultation for
Kalobics; is on the Pharmaxis advisory committee; is on the ad-hoc
advisory committee for Merck and GlaxoSmithKline; has provided
consultation for Genentech and Johnson & Johnson; and has received
research support from GlaxoSmithKline and Genentech. C. A. Camargo, Jr,
is a consultant for Dey, Genentech, Merck, Novartis, and Pfizer; and has
received research support from GlaxoSmithKline and Sanofi-Aventis. J.
Gern is on the Scientific Advisory Board and has stock options in 3V
Biosciences, and has received consulting fees from Centocor, Boehringer
Ingelheim, GlaxoSmithKline, Biota, MedImmune, and Theraclone. P. W.
Heymann has received research support from the NIH and Novartis. F. D.
Martinez has consulted for MedImmune and received lecture honorarium
from Abbott. W. G. Teague is a speaker for Merck and Genentech, and has
received research support from the NIH/NHLBI and the American Lung
Association. C. Blaisdell is on the American Academy of Pediatrics
Executive Board and is an abstract reviewer for the Pediatric Academic
Society. The rest of the authors declare that they have no relevant
conflicts of interest.
NR 138
TC 66
Z9 67
U1 2
U2 14
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD MAR
PY 2012
VL 129
IS 3
SU S
BP S34
EP S48
DI 10.1016/j.jaci.2011.12.983
PG 15
WC Allergy; Immunology
SC Allergy; Immunology
GA 901OL
UT WOS:000300976600004
PM 22386508
ER
PT J
AU Krishnan, JA
Lemanske, RF
Canino, GJ
Elward, KS
Kattan, M
Matsui, EC
Mitchell, H
Sutherland, ER
Minnicozzi, M
AF Krishnan, Jerry A.
Lemanske, Robert F., Jr.
Canino, Glorisa J.
Elward, Kurtis S.
Kattan, Meyer
Matsui, Elizabeth C.
Mitchell, Herman
Sutherland, E. Rand
Minnicozzi, Michael
TI Asthma outcomes: Symptoms
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Article
DE Asthma Symptom Utility Index; Asthma Symptom Diary Scales; Pediatric
Asthma Caregiver Diary
ID LEUKOTRIENE RECEPTOR ANTAGONIST; POORLY CONTROLLED ASTHMA; MILD
PERSISTENT ASTHMA; PRESCHOOL-CHILDREN; INDUCED BRONCHOCONSTRICTION;
PATIENT PREFERENCES; ALLERGIC RHINITIS; CHILDHOOD ASTHMA;
CLINICAL-TRIALS; UTILITY INDEX
AB Background: Respiratory symptoms are commonly used to assess the impact of patient-centered interventions.
Objective: At the request of National Institutes of Health (NIH) institutes and other federal agencies, an expert group was convened to propose which measurements of asthma symptoms should be used as a standardized measure in future clinical research studies.
Methods: Asthma symptom instruments were classified as daily diaries (prospectively recording symptoms between research visits) or retrospective questionnaires (completed at research visits). We conducted a systematic search in PubMed and a search for articles that cited key studies describing development of instruments. We classified outcome instruments as either core (required in future studies), supplemental (used according to study aims and standardized), or emerging (requiring validation and standardization). This work was discussed at an NIH-organized workshop in March 2010 and finalized in September 2011.
Results: Four instruments (3 daily diaries, 1 for adults and 2 for children; and 1 retrospective questionnaire for adults) were identified. Minimal clinically important differences have not been established for these instruments, and validation studies were only conducted in a limited number of patient populations. Validity of existing instruments may not be generalizable across racial-ethnic or other subgroups.
Conclusions: An evaluation of symptoms should be a core asthma outcome measure in clinical research. However, available instruments have limitations that preclude selection of a core instrument. The working group participants propose validation studies in diverse populations, comparisons of diaries versus retrospective questionnaires, and evaluations of symptom assessment alone versus composite scores of asthma control. (J Allergy Clin Immunol 2012; 129: S124-35.)
C1 [Minnicozzi, Michael] NIAID, DAIT, NIH, Bethesda, MD 20892 USA.
[Krishnan, Jerry A.] Univ Illinois, Chicago, IL USA.
[Lemanske, Robert F., Jr.] Univ Wisconsin, Madison, WI 53706 USA.
[Canino, Glorisa J.] Univ Puerto Rico, San Juan, PR 00936 USA.
[Elward, Kurtis S.] Family Med Albermarle, Charlottesville, VA USA.
[Kattan, Meyer] Columbia Univ, Med Ctr, New York, NY USA.
[Matsui, Elizabeth C.] Johns Hopkins Univ, Baltimore, MD USA.
[Mitchell, Herman] Rho Fed Syst Div Inc, Chapel Hill, NC USA.
[Sutherland, E. Rand] Natl Jewish Hlth, Denver, CO USA.
RP Minnicozzi, M (reprint author), NIAID, DAIT, NIH, 6610 Rockledge Dr, Bethesda, MD 20892 USA.
EM minnicozzmi@niaid.nih.gov
FU National Institute of Allergy and Infectious Diseases; National Heart,
Lung, and Blood Institute; Eunice Kennedy Shriver National Institute of
Child Health and Human Development; National Institute of Environmental
Health Sciences; Agency for Healthcare Research and Quality; Merck
Childhood Asthma Network; Robert Wood Johnson Foundation; US
Environmental Protection Agency; National Asthma Control Initiative;
NIH-NIAID
FX The Asthma Outcomes workshop was funded by contributions from the
National Institute of Allergy and Infectious Diseases; the National
Heart, Lung, and Blood Institute; the Eunice Kennedy Shriver National
Institute of Child Health and Human Development; the National Institute
of Environmental Health Sciences; the Agency for Healthcare Research and
Quality; and the Merck Childhood Asthma Network, as well as by a grant
from the Robert Wood Johnson Foundation. Contributions from the National
Heart, Lung, and Blood Institute; the National Institute of Allergy and
Infectious Diseases; the Eunice Kennedy Shriver National Institute of
Child Health and Human Development; the National Institute of
Environmental Health Sciences, and the US Environmental Protection
Agency funded the publication of this article and all other articles in
this supplement.; Disclosure of potential conflict of interest: R. F.
Lemanske, Jr, is a speaker for Merck and AstraZeneca and has consulted
for AstraZeneca, Map Pharmaceuticals, Gray Consulting, Smith Research
Inc, Merck Childhood Asthma Network, Novartis, Quintiles/Innovax, RC
Horowitz & Co Inc. Scienomics, Scientific Therapeutics, Cognimed Inc, SA
Boney and Associates, GlaxoSmithKline, and Double Helix Development Inc.
K. S. Elward is a speaker on guidelines implementation for Merck; has
received research support from the National Asthma Control Initiative;
is a member of the Virginia Asthma Coalition; and is a member of the
National Asthma Education and Prevention Program Coordination Committee.
M. Kattan has received research support from the NIH-NIAID. The rest of
the authors declare that they have no relevant conflicts of interest.
NR 54
TC 31
Z9 31
U1 1
U2 5
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD MAR
PY 2012
VL 129
IS 3
SU S
BP S124
EP S135
DI 10.1016/j.jaci.2011.12.981
PG 12
WC Allergy; Immunology
SC Allergy; Immunology
GA 901OL
UT WOS:000300976600008
PM 22386505
ER
PT J
AU Rand, CS
Wright, RJ
Cabana, MD
Foggs, MB
Halterman, JS
Olson, L
Vollmer, WM
Wilson, SR
Taggart, V
AF Rand, Cynthia S.
Wright, Rosalind J.
Cabana, Michael D.
Foggs, Michael B.
Halterman, Jill S.
Olson, Lynn
Vollmer, William M.
Wilson, Sandra R.
Taggart, Virginia
TI Mediators of asthma outcomes
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Article
DE Adherence; self-management skills; asthma patient education; stress
ID SELF-MANAGEMENT PROGRAM; POSTNATAL DEPRESSION SCALE; STRESSFUL LIFE
EVENTS; MEDICATION ADHERENCE; INHALED CORTICOSTEROIDS;
PREDICTIVE-VALIDITY; PERCEIVED STRESS; CHRONIC DISEASE; CHILDREN;
VALIDATION
AB Background: Patient adherence, the level of asthma self-management skills, exposure to stress, and depression can have considerable influence on a wide range of asthma outcomes and thus are considered asthma outcome mediators.
Objective: National Institutes of Health institutes and other federal agencies convened an expert group to recommend standardized measures for 7 domains of asthma clinical research outcomes measures. Although the review of mediators of these outcomes was not within the scope of any specific outcome topic, a brief summary is presented so that researchers might consider potential mediators.
Methods: We prepared a summary of key mediators of asthma outcomes based on expertise and knowledge of the literature.
Results: The rationale for including measures of adherence, self-management skills, and exposures to stress in asthma clinical research is presented, along with a brief review of instruments for collecting this information from clinical research participants.
Conclusions: Appropriate measurement of adherence, self-management skills, and exposures to stress will enhance characterization of study participants and provide information about the potential impact these factors can have on mediating the effects of treatment interventions. (J Allergy Clin Immunol 2012; 129: S136-41.)
C1 [Taggart, Virginia] NHLBI, DLD, NIH, Bethesda, MD 20892 USA.
[Rand, Cynthia S.] Johns Hopkins Univ, Baltimore, MD USA.
[Wright, Rosalind J.] Harvard Univ, Sch Med, Boston, MA USA.
[Cabana, Michael D.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Foggs, Michael B.] Advocate Hlth Care, Oak Brook, IL USA.
[Halterman, Jill S.] Univ Rochester, Rochester, NY 14627 USA.
[Olson, Lynn] Amer Acad Pediat, Elk Grove Village, IL USA.
[Vollmer, William M.] Kaiser Permanente, Ctr Hlth Res, Portland, OR USA.
[Wilson, Sandra R.] Palo Alto Med Fdn, Res Inst, Palo Alto, CA 94301 USA.
RP Taggart, V (reprint author), NHLBI, DLD, NIH, 6701 Rockledge Dr, Bethesda, MD 20892 USA.
EM taggartv@nih.gov
RI Osborne, Nicholas/N-4915-2015
OI Osborne, Nicholas/0000-0002-6700-2284
FU National Institute of Allergy and Infectious Diseases; National Heart,
Lung, and Blood Institute; Eunice Kennedy Shriver National Institute of
Child Health and Human Development; National Institute of Environmental
Health Sciences; Agency for Healthcare Research and Quality; Merck
Childhood Asthma Network; Robert Wood Johnson Foundation; US
Environmental Protection Agency
FX The Asthma Outcomes workshop was funded by contributions from the
National Institute of Allergy and Infectious Diseases; the National
Heart, Lung, and Blood Institute; the Eunice Kennedy Shriver National
Institute of Child Health and Human Development; the National Institute
of Environmental Health Sciences; the Agency for Healthcare Research and
Quality; and the Merck Childhood Asthma Network, as well as by a grant
from the Robert Wood Johnson Foundation. Contributions from the National
Heart, Lung, and Blood Institute; the National Institute of Allergy and
Infectious Diseases; the Eunice Kennedy Shriver National Institute of
Child Health and Human Development; the National Institute of
Environmental Health Sciences; and the US Environmental Protection
Agency funded the publication of this article and for all other articles
in this supplement.
NR 79
TC 28
Z9 28
U1 5
U2 11
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD MAR
PY 2012
VL 129
IS 3
SU S
BP S136
EP S141
DI 10.1016/j.jaci.2011.12.987
PG 6
WC Allergy; Immunology
SC Allergy; Immunology
GA 901OL
UT WOS:000300976600009
PM 22386506
ER
PT J
AU Szefler, SJ
Wenzel, S
Brown, R
Erzurum, SC
Fahy, JV
Hamilton, RG
Hunt, JF
Kita, H
Liu, AH
Panettieri, RA
Schleimer, RP
Minnicozzi, M
AF Szefler, Stanley J.
Wenzel, Sally
Brown, Robert
Erzurum, Serpil C.
Fahy, John V.
Hamilton, Robert G.
Hunt, John F.
Kita, Hirohito
Liu, Andrew H.
Panettieri, Reynold A., Jr.
Schleimer, Robert P.
Minnicozzi, Michael
TI Asthma outcomes: Biomarkers
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Article
DE Multiallergen screen; fractional exhaled nitric oxide; sputum
eosinophils; total eosinophils; IgE; urinary leukotriene E-4
ID EXHALED NITRIC-OXIDE; SKIN-TEST REACTIVITY; EOSINOPHILIC AIRWAY
INFLAMMATION; URINARY LEUKOTRIENE E-4; SPUTUM CELL COUNTS;
HEALTHY-SUBJECTS; CHILDHOOD ASTHMA; REFERENCE VALUES; INHALED
CORTICOSTEROIDS; PERSISTENT ASTHMA
AB Background: Measurement of biomarkers has been incorporated within clinical research studies of asthma to characterize the population and associate the disease with environmental and therapeutic effects.
Objective: National Institutes of Health institutes and federal agencies convened an expert group to propose which biomarkers should be assessed as standardized asthma outcomes in future clinical research studies.
Methods: We conducted a comprehensive search of the literature to identify studies that developed and/or tested asthma biomarkers. We identified biomarkers relevant to the underlying disease process progression and response to treatment. We classified the biomarkers as either core (required in future studies), supplemental (used according to study aims and standardized), or emerging (requiring validation and standardization). This work was discussed at an National Institutes of Health-organized workshop convened in March 2010 and finalized in September 2011.
Results: Ten measures were identified; only 1, multiallergen screening to define atopy, is recommended as a core asthma outcome. Complete blood counts to measure total eosinophils, fractional exhaled nitric oxide (FENO), sputum eosinophils, urinary leukotrienes, and total and allergen-specific IgE are recommended as supplemental measures. Measurement of sputum polymorphonuclear leukocytes and other analytes, cortisol measures, airway imaging, breath markers, and system-wide studies (eg, genomics, proteomics) are considered as emerging outcome measures.
Conclusion: The working group participants propose the use of multiallergen screening in all asthma clinical trials to characterize study populations with respect to atopic status. Blood, sputum, and urine specimens should be stored in biobanks, and standard procedures should be developed to harmonize sample collection for clinical trial biorepositories. (J Allergy Clin Immunol 2012; 129:S9-23.)
C1 [Minnicozzi, Michael] NIAID, DAIT, NIH, Bethesda, MD 20892 USA.
[Szefler, Stanley J.; Liu, Andrew H.] Natl Jewish Hlth, Denver, CO USA.
[Wenzel, Sally] Univ Pittsburgh, Pittsburgh, PA 15260 USA.
[Brown, Robert; Hamilton, Robert G.] Johns Hopkins Univ, Baltimore, MD USA.
[Erzurum, Serpil C.] Cleveland Clin Fdn, Cleveland, OH USA.
[Fahy, John V.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Hunt, John F.] Univ Virginia, Charlottesville, VA USA.
[Kita, Hirohito] Mayo Clin Rochester, Rochester, MN USA.
[Panettieri, Reynold A., Jr.] Univ Penn, Philadelphia, PA 19104 USA.
[Schleimer, Robert P.] Northwestern Univ, Chicago, IL 60611 USA.
RP Minnicozzi, M (reprint author), NIAID, DAIT, NIH, 6610 Rockledge Dr, Bethesda, MD 20892 USA.
EM minnicozzim@niaid.nih.gov
FU National Institute of Allergy and Infectious Diseases; National Heart,
Lung, and Blood Institute; Eunice Kennedy Shriver National Institute of
Child Health and Human Development; National Institute of Environmental
Health Sciences; Agency for Healthcare Research and Quality; Merck
Childhood Asthma Network; Robert Wood Johnson Foundation; US
Environmental Protection Agency; NIH (NHLBI, NIAID, NIEHS);
Environmental Protection Agency; NIH (NHLBI); NIH (NIAID); Genentech;
NIH-NIAID; Altrea; AstraZeneca; Johnson Johnson; Merck; Roche
FX The Asthma Outcomes workshop was funded by contributions from the
National Institute of Allergy and Infectious Diseases; the National
Heart, Lung, and Blood Institute; the Eunice Kennedy Shriver National
Institute of Child Health and Human Development; the National Institute
of Environmental Health Sciences; the Agency for Healthcare Research and
Quality; and the Merck Childhood Asthma Network, as well as by a grant
from the Robert Wood Johnson Foundation. Contributions from the National
Heart, Lung, and Blood Institute; the National Institute of Allergy and
Infectious Diseases; the Eunice Kennedy Shriver National Institute of
Child Health and Human Development; the National Institute of
Environmental Health Sciences; and the US Environmental Protection
Agency funded the publication of this article and all other articles in
this supplement.; Disclosure of potential conflict of interest: S. J.
Szefler is a consultant for GlaxoSmithKline, Genentech, Merck,
Boehringer-Ingelheim, Novartis, and Schering-Plough; and has received
research support from the NIH (NHLBI, NIAID, NIEHS) and the
Environmental Protection Agency. J. V. Fahy is on the Cytokinetics
Scientific advisory board; has received consulting fees from Amgen,
Gilcad, Five Prime Therapeutics, Merck, Regeneron Pharmaceuticals,
Portola Pharmaceuticals; and has received research support from the NIH
(NHLBI and NIAID) and Genentech. J. F. Hunt is on the Pulse Health LLC
advisory board; is founder of Respiratory Research, Inc; has received
research support from the NIH-NIAID and Altrea; and is Chair of the
AAAAI Asthma Diagnosis and Pharmacotherapeutics Committee and Cough
Committee. A. H. Liu has received speaker honoraria from Merck; is on
the Data Safety Monitoring Board for GlaxoSmithKline; and is a
consultant for DBV. R. A. Panettieri, Jr, is a consultant for Johnson &
Johnson, Forest Pharmaceuticals, Genentech, and Merck; and has received
research support from AstraZeneca, Johnson & Johnson, Merck, and Roche.
R. P. Schleimer is a consultant for GlaxoSmithKline and Intersect ENT.
The rest of the authors declare that they have no relevant conflicts of
interest.
NR 178
TC 128
Z9 130
U1 3
U2 26
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD MAR
PY 2012
VL 129
IS 3
SU S
BP S9
EP S23
DI 10.1016/j.jaci.2011.12.979
PG 15
WC Allergy; Immunology
SC Allergy; Immunology
GA 901OL
UT WOS:000300976600002
PM 22386512
ER
PT J
AU Tepper, RS
Wise, RS
Covar, R
Irvin, CG
Kercsmar, CM
Kraft, M
Liu, MC
O'Connor, GT
Peters, SP
Sorkness, R
Togias, A
AF Tepper, Robert S.
Wise, Robert S.
Covar, Ronina
Irvin, Charles G.
Kercsmar, Carolyn M.
Kraft, Monica
Liu, Mark C.
O'Connor, George T.
Peters, Stephen P.
Sorkness, Ronald
Togias, Alkis
TI Asthma outcomes: Pulmonary physiology
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Article
DE Spirometry; airway responsiveness; peak expiratory flow monitoring; lung
volumes; gas exchange
ID PEAK EXPIRATORY FLOW; EXERCISE-INDUCED BRONCHOCONSTRICTION; COLD-AIR
CHALLENGE; EXHALED NITRIC-OXIDE; METHACHOLINE-INDUCED
BRONCHOCONSTRICTION; NONSPECIFIC BRONCHIAL RESPONSIVENESS;
LEUKOTRIENE-RECEPTOR ANTAGONIST; NASAL INSPIRATORY FLOW; LUNG-FUNCTION;
BRONCHODILATOR RESPONSIVENESS
AB Background: Outcomes of pulmonary physiology have a central place in asthma clinical research.
Objective: At the request of National Institutes of Health (NIH) institutes and other federal agencies, an expert group was convened to provide recommendations on the use of pulmonary function measures as asthma outcomes that should be assessed in a standardized fashion in future asthma clinical trials and studies to allow for cross-study comparisons.
Methods: Our subcommittee conducted a comprehensive search of PubMed to identify studies that focused on the validation of various airway response tests used in asthma clinical research. The subcommittee classified the instruments as core (to be required in future studies), supplemental (to be used according to study aims and in a standardized fashion), or emerging (requiring validation and standardization). This work was discussed at an NIH-organized workshop in March 2010 and finalized in September 2011.
Results: A list of pulmonary physiology outcomes that applies to both adults and children older than 6 years was created. These outcomes were then categorized into core, supplemental, and emerging. Spirometric outcomes (FEV1, forced vital capacity, and FEV1/forced vital capacity ratio) are proposed as core outcomes for study population characterization, for observational studies, and for prospective clinical trials. Bronchodilator reversibility and prebronchodilator and postbronchodilator FEV1 also are core outcomes for study population characterization and observational studies.
Conclusions: The subcommittee considers pulmonary physiology outcomes of central importance in asthma and proposes spirometric outcomes as core outcomes for all future NIH-initiated asthma clinical research. (J Allergy Clin Immunol 2012; 129: S65-87.)
C1 [Togias, Alkis] NIAID, DAIT, NIH, Bethesda, MD 20892 USA.
[Tepper, Robert S.] Indiana Univ, Indianapolis, IN 46204 USA.
[Wise, Robert S.; Liu, Mark C.] Johns Hopkins Univ, Baltimore, MD USA.
[Covar, Ronina] Natl Jewish Hlth, Denver, CO USA.
[Irvin, Charles G.] Univ Vermont, Burlington, VT 05405 USA.
[Kercsmar, Carolyn M.] Cincinnati Childrens Hosp, Cincinnati, OH USA.
[Kraft, Monica] Duke Univ, Durham, NC 27706 USA.
[O'Connor, George T.] Boston Univ, Boston, MA 02215 USA.
[Peters, Stephen P.] Wake Forest Univ, Winston Salem, NC 27109 USA.
[Sorkness, Ronald] Univ Wisconsin, Madison, WI 53706 USA.
RP Togias, A (reprint author), NIAID, DAIT, NIH, 6610 Rockledge Dr, Bethesda, MD 20892 USA.
EM togiasa@niaid.nih.gov
OI O'Connor, George/0000-0002-6476-3926; Wise, Robert/0000-0002-8353-2349
FU National Institute of Allergy and Infectious Diseases; National Heart,
Lung, and Blood Institute; Eunice Kennedy Shriver National Institute of
Child Health and Human Development; National Institute of Environmental
Health Sciences; Agency for Healthcare Research and Quality; Merck
Childhood Asthma Network; Robert Wood Johnson Foundation; US
Environmental Protection Agency; GlaxoSmithKline; Boehringer-Ingelheim;
Merck; Forest; NIH; American Lung Association; Asthmatx; Eumedics;
Novartis; Genentech; MedImmune; Sanofi-Aventis; Amgen
FX The Asthma Outcomes work shop was funded by contributions from the
National Institute of Allergy and Infectious Diseases; the National
Heart, Lung, and Blood Institute; the Eunice Kennedy Shriver National
Institute of Child Health and Human Development; the National Institute
of Environmental Health Sciences; the Agency for Healthcare Research and
Quality; and the Merck Childhood Asthma Network, as well as by a grant
from the Robert Wood Johnson Foundation. Contributions from the National
Heart, Lung, and Blood Institute; the National Institute of Allergy and
Infectious Diseases; the Eunice Kennedy Shriver National Institute of
Child Health and Human Development; the National Institute of
Environmental Health Sciences; and the US Environmental Protection
Agency funded the publication of this article and all other articles in
this supplement.; Disclosure of potential conflict of interest: R. S.
Tepper has received research support from the NHLBI. R. S. Wise is a
consultant for GlaxoSmithKline, AstraZeneca, Novartis,
Boehringer-Ingelheim, Merck, and Sunovion; and has received research
support from GlaxoSmithKline, Boehringer-Ingelheim, Merck, and Forest.
R. Covar has received research support from the NHLBI. C. G. Irvin has
received research support from the NIH and the American Lung
Association. M. Kraft has received research support from
GlaxoSmithKline, Merck, Asthmatx, Eumedics, Novartis, and Genentech. M.
C. Liu has received research support from GlaxoSmithKline, MedImmune,
Sanofi-Aventis, and Amgen. G. T. O'Connor is a consultant for Sunovion
Inc and has received research support from Novartis. R. Sorkness has
received research support from the NIH. The rest of the authors declare
that they have no relevant conflicts of interest.
NR 225
TC 31
Z9 33
U1 2
U2 13
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD MAR
PY 2012
VL 129
IS 3
SU S
BP S65
EP S87
DI 10.1016/j.jaci.2011.12.986
PG 23
WC Allergy; Immunology
SC Allergy; Immunology
GA 901OL
UT WOS:000300976600006
PM 22386510
ER
PT J
AU Wilson, SR
Rand, CS
Cabana, MD
Foggs, MB
Halterman, JS
Olson, L
Vollmer, WM
Wright, RJ
Taggart, V
AF Wilson, Sandra R.
Rand, Cynthia S.
Cabana, Michael D.
Foggs, Michael B.
Halterman, Jill S.
Olson, Lynn
Vollmer, William M.
Wright, Rosalind J.
Taggart, Virginia
TI Asthma outcomes: Quality of life
SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
LA English
DT Article
DE Asthma burden; asthma-related well-being; health perceptions; health
status; patient-reported outcomes
ID GEORGES-RESPIRATORY-QUESTIONNAIRE; CHILDRENS HEALTH SURVEY; GENERIC CORE
SCALES; PEDIATRIC-ASTHMA; ADULT ASTHMA; CHILDHOOD ASTHMA; YOUNG-ADULTS;
SELF-MANAGEMENT; DISEASE-CONTROL; LONGITUDINAL CHANGES
AB Background: "Asthma-related quality of life" (QOL) refers to the perceived impact that asthma has on the patient's QOL.
Objective: National Institutes of Health institutes and other federal agencies convened an expert group to recommend standardized measures of the impact of asthma on QOL for use in future asthma clinical research.
Methods: We reviewed published documentation regarding the development and psychometric evaluation; clinical research use since 2000; and extent to which the content of each existing QOL instrument provides a unique, reliable, and valid assessment of the intended construct. We classified instruments as core (required in future studies), supplemental (used according to the study's aims and standardized), or emerging (requiring validation and standardization). This work was discussed at an National Institutes of Health-organized workshop convened in March 2010 and finalized in September 2011.
Results: Eleven instruments for adults and 6 for children were identified for review. None qualified as core instruments because they predominantly measured indicators of asthma control (symptoms and/or functional status); failed to provide a distinct, reliable score measuring all key dimensions of the intended construct; and/or lacked adequate psychometric data.
Conclusions: In the absence of existing instruments that meet the stated criteria, currently available instruments are classified as either supplemental or emerging. Research is strongly recommended to develop and evaluate instruments that provide a distinct, reliable measure of the patient's perception of the impact of asthma on all of the key dimensions of QOL, an important outcome that is not captured in other outcome measures. (J Allergy Clin Immunol 2012; 129: S88-123.)
C1 [Taggart, Virginia] NHLBI, DLD, NIH, Bethesda, MD 20892 USA.
[Wilson, Sandra R.] Palo Alto Med Fdn, Res Inst, Palo Alto, CA 94301 USA.
[Rand, Cynthia S.] Johns Hopkins Univ, Baltimore, MD USA.
[Cabana, Michael D.] Univ Calif San Francisco, San Francisco, CA 94143 USA.
[Foggs, Michael B.] Advocate Hlth Care, Oak Brook, IL USA.
[Halterman, Jill S.] Univ Rochester, Rochester, NY 14627 USA.
[Olson, Lynn] Amer Acad Pediat, Elk Grove Village, IL USA.
[Vollmer, William M.] Kaiser Permanente, Portland, OR USA.
[Wright, Rosalind J.] Harvard Univ, Sch Med, Boston, MA USA.
RP Taggart, V (reprint author), NHLBI, DLD, NIH, 6701 Rockledge Dr, Bethesda, MD 20892 USA.
EM taggartv@nih.gov
FU National Institute of Allergy and Infectious Diseases; National Heart,
Lung, and Blood Institute; Eunice Kennedy Shriver National Institute of
Child Health and Human Development; National Institute of Environmental
Health Sciences; Agency for Healthcare Research and Quality; Merck
Childhood Asthma Network; Robert Wood Johnson Foundation; US
Environmental Protection Agency
FX The Asthma Outcomes workshop was funded by contributions from the
National Institute of Allergy and Infectious Diseases; the National
Heart, Lung, and Blood Institute; the Eunice Kennedy Shriver National
Institute of Child Health and Human Development; the National Institute
of Environmental Health Sciences; the Agency for Healthcare Research and
Quality; and the Merck Childhood Asthma Network, as well as by a grant
from the Robert Wood Johnson Foundation. Contributions from the National
Heart, Lung, and Blood Institute; the National Institute of Allergy and
Infectious Diseases; the Eunice Kennedy Shriver National Institute of
Child Health and Human Development; the National Institute of
Environmental Health Sciences; and the US Environmental Protection
Agency funded the publication of this article and all other articles in
this supplement.
NR 146
TC 45
Z9 45
U1 1
U2 14
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0091-6749
J9 J ALLERGY CLIN IMMUN
JI J. Allergy Clin. Immunol.
PD MAR
PY 2012
VL 129
IS 3
SU S
BP S88
EP S123
DI 10.1016/j.jaci.2011.12.988
PG 36
WC Allergy; Immunology
SC Allergy; Immunology
GA 901OL
UT WOS:000300976600007
PM 22386511
ER
PT J
AU Neunuebel, MR
Mohammadi, S
Jarnik, M
Machner, MP
AF Neunuebel, M. Ramona
Mohammadi, Sina
Jarnik, Michal
Machner, Matthias P.
TI Legionella pneumophila LidA Affects Nucleotide Binding and Activity of
the Host GTPase Rab1
SO JOURNAL OF BACTERIOLOGY
LA English
DT Article
ID EFFECTOR PROTEIN DRRA; ENDOPLASMIC-RETICULUM; INTRACELLULAR SURVIVAL;
TRANSLOCATED SUBSTRATE; GUANINE-NUCLEOTIDES; VESICULAR TRANSPORT; GOLGI
COMPARTMENTS; PLASMA-MEMBRANE; HUMAN-MONOCYTES; EXCHANGE FACTOR
AB Legionella pneumophila, the causative agent of a severe pneumonia known as Legionnaires' disease, intercepts material from host cell membrane transport pathways to create a specialized vacuolar compartment that supports bacterial replication. Delivery of bacterial effector proteins into the host cell requires the Dot/Icm type IV secretion system. Several effectors, including SidM, SidD, and LepB, were shown to target the early secretory pathway by manipulating the activity of the host GTPase Rab1. While the function of these effectors has been well characterized, the role of another Rab1-interacting protein from L. pneumophila, the effector protein LidA, is poorly understood. Here, we show that LidA binding to Rab1 stabilized the Rab1-guanosine nucleotide complex, protecting it from inactivation by GTPase-activating proteins (GAPs) and from nucleotide extraction. The protective effect of LidA on the Rab1-guanine nucleotide complex was concentration dependent, consistent with a 1:1 stoichiometry of the LidA-Rab1 complex. The central coiled-coil region of LidA was sufficient for Rab1 binding and to prevent GAP-mediated inactivation or nucleotide extraction from Rab1. In addition, the central region mediated binding to phosphatidylinositol 3-phosphate and other phosphoinositides. When bound to Rab1, LidA interfered with the covalent modification of Rab1 by phosphocholination or AMPylation, and it also blocked de-AMPylation of Rab1 by SidD and dephosphocholination by Lem3. Based on these findings, we propose a role for LidA in bridging the membrane of the Legionella-containing vacuole (LCV) with that of secretory transport vesicles surrounding the LCV.
C1 [Neunuebel, M. Ramona; Jarnik, Michal; Machner, Matthias P.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Metab Program, NIH, Bethesda, MD USA.
[Mohammadi, Sina] Tufts Univ, Sch Med, Dept Mol Biol & Microbiol, Boston, MA 02111 USA.
RP Machner, MP (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Cell Biol & Metab Program, NIH, Bethesda, MD USA.
EM machnerm@mail.nih.gov
RI Machner, Matthias/G-2758-2015;
OI Machner, Matthias/0000-0002-6971-7451
FU NIH
FX This work was supported by the Intramural Research Program of the NIH.
NR 52
TC 27
Z9 30
U1 0
U2 5
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 MAR
PY 2012
VL 194
IS 6
BP 1389
EP 1400
DI 10.1128/JB.06306-11
PG 12
WC Microbiology
SC Microbiology
GA 899WI
UT WOS:000300846900012
PM 22228731
ER
PT J
AU Nguyen, HT
Torian, U
Faulk, K
Mather, K
Engle, RE
Thompson, E
Bonkovsky, HL
Emerson, SU
AF Nguyen, H. T.
Torian, U.
Faulk, K.
Mather, K.
Engle, R. E.
Thompson, E.
Bonkovsky, H. L.
Emerson, S. U.
TI A naturally occurring human/hepatitis E recombinant virus predominates
in serum but not in faeces of a chronic hepatitis E patient and has a
growth advantage in cell culture
SO JOURNAL OF GENERAL VIROLOGY
LA English
DT Article
ID ENZYME-IMMUNOASSAY; EFFICIENT; ANTIBODIES; INFECTION; THERAPY; STRAINS;
SYSTEM; BLOOD; HEV
AB Hepatitis E virus is the aetiological agent of acute hepatitis E, a self-limiting disease prevalent in developing countries. Molecular analysis of viral genomic RNA from a chronically infected patient confirmed the recent discovery that chronic infection correlated with extensive diversification of the virus quasispecies: the hypervariable region of some virus genomes in this USA patient contained large continuous deletions and a minor proportion of genomes in faeces and serum had acquired a mammalian sequence that encoded 39 aa of S19 ribosomal protein fused to the virus non-structural protein. Genomes with this insert were selected during virus passage in cultured cells to become the predominant species, suggesting that the inserted sequence promoted virus growth. The results demonstrated that hepatitis E virus can mutate dramatically during a prolonged infection and suggests it may be important to prevent or cure chronic infections before new variants with unpredictable properties arise.
C1 [Nguyen, H. T.; Torian, U.; Faulk, K.; Mather, K.; Engle, R. E.; Emerson, S. U.] NIAID, Mol Hepatitis Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
[Thompson, E.] Carolinas Digest Hlth Associates, Charlotte, NC 28211 USA.
[Bonkovsky, H. L.] Carolinas Hlth Care Syst, Ctr Liver, Charlotte, NC 28203 USA.
[Bonkovsky, H. L.] Univ N Carolina, Charlotte, NC 28203 USA.
[Bonkovsky, H. L.] Univ Connecticut, Farmington, CT 06030 USA.
RP Emerson, SU (reprint author), NIAID, Mol Hepatitis Sect, Infect Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM semerson@niaid.nih.gov
FU National Institutes of Health, National Institute of Allergy and
Infectious Diseases
FX This research was supported by the Intramural Research Program of the
National Institutes of Health, National Institute of Allergy and
Infectious Diseases. This work was carried out under an approved
protocol of the Carolinas Medical Center, IRB 10-0709B, with the
informed consent of the patient.
NR 20
TC 22
Z9 23
U1 1
U2 2
PU SOC GENERAL MICROBIOLOGY
PI READING
PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG,
BERKS, ENGLAND
SN 0022-1317
J9 J GEN VIROL
JI J. Gen. Virol.
PD MAR
PY 2012
VL 93
BP 526
EP 530
DI 10.1099/vir.0.037259-0
PN 3
PG 5
WC Biotechnology & Applied Microbiology; Virology
SC Biotechnology & Applied Microbiology; Virology
GA 902JE
UT WOS:000301033600007
PM 22113007
ER
PT J
AU Marshall, LJ
Moore, LD
Mirsky, MM
Major, EO
AF Marshall, Leslie J.
Moore, Lisa D.
Mirsky, Matthew M.
Major, Eugene O.
TI JC virus promoter/enhancers contain TATA box-associated Spi-B-binding
sites that support early viral gene expression in primary astrocytes
SO JOURNAL OF GENERAL VIROLOGY
LA English
DT Article
ID PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; LARGE T-ANTIGEN;
TRANSCRIPTIONAL CONTROL REGION; HUMAN NEUROTROPIC VIRUS; LARGE
TUMOR-ANTIGEN; GLIAL-CELLS; REGULATORY REGION; MULTIPLE-SCLEROSIS;
ENHANCER ACTIVITY; PROMOTER ACTIVITY
AB JC virus (JCV) is the aetiological agent of the demyelinating disease progressive multifocal leukoencephalopathy, an AIDS defining illness and serious complication of mAb therapies. Initial infection probably occurs in childhood. In the working model of dissemination, virus persists in the kidney and lymphoid tissues until immune suppression/modulation causes reactivation and trafficking to the brain where JCV replicates in oligodendrocytes. JCV infection is regulated through binding of host factors such as Spi-B to, and sequence variation in the non-coding control region (NCCR). Although NCCR sequences differ between sites of persistence and pathogenesis, evidence suggests that the virus that initiates infection in the brain disseminates via B-cells derived from latently infected haematopoietic precursors in the bone marrow. Spi-B binds adjacent to TATA boxes in the promoter/enhancer of the PML-associated JCV Mad-1 and Mad-4 viruses but not the non-pathogenic, kidney-associated archetype. The Spi-B-binding site of Mad-1/Mad-4 differs from that of archetype by a single nucleotide, AAAAGGGAAGGGA to AAAAGGGAAGGTA. Point mutation of the Mad-1 Spi-B site reduced early viral protein large T-antigen expression by up to fourfold. Strikingly, the reverse mutation in the archetype NCCR increased large T-antigen expression by 10-fold. Interestingly, Spi-B protein binds the NCCR sequence flanking the viral promoter/enhancer, but these sites are not essential for early viral gene expression. The effect of mutating Spi-B-binding sites within the JCV promoter/enhancer on early viral gene expression strongly suggests a role for Spi-B binding to the viral promoter/enhancer in the activation of early viral gene expression.
C1 [Marshall, Leslie J.; Moore, Lisa D.; Mirsky, Matthew M.; Major, Eugene O.] Natl Inst Neurol Disorders & Stroke, Lab Mol Med & Neurosci, NIH, Bethesda, MD 20892 USA.
RP Major, EO (reprint author), Natl Inst Neurol Disorders & Stroke, Lab Mol Med & Neurosci, NIH, Bethesda, MD 20892 USA.
EM majorg@ninds.nih.gov
FU Laboratory of Molecular Medicine and Neuroscience at the NINDS; NINDS
FX We thank Francoise Moreau-Gachelin of the Institut Curie (Paris, France)
for generously providing polyclonal rabbit Spi-B antiserum and human
Spi-B plasmid. We thank the DNA sequencing facility at the National
Institute of Neurological Disorders and Stroke (NINDS) for aid in
sequencing of mutant viral plasmids. We thank all of the members of the
Laboratory of Molecular Medicine and Neuroscience at the NINDS for their
hard work, support, and valuable input. The intramural program at the
NINDS provided support for this work.
NR 65
TC 16
Z9 17
U1 0
U2 0
PU SOC GENERAL MICROBIOLOGY
PI READING
PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG,
BERKS, ENGLAND
SN 0022-1317
J9 J GEN VIROL
JI J. Gen. Virol.
PD MAR
PY 2012
VL 93
BP 651
EP 661
DI 10.1099/vir.0.035832-0
PN 3
PG 11
WC Biotechnology & Applied Microbiology; Virology
SC Biotechnology & Applied Microbiology; Virology
GA 902JE
UT WOS:000301033600023
PM 22071512
ER
PT J
AU Srinivasalu, H
Barnes, MG
Layh-Schmitt, G
Ward, MM
Colbert, RA
AF Srinivasalu, Hemalatha
Barnes, Michael G.
Layh-Schmitt, Gerlinde
Ward, Michael M.
Colbert, Robert A.
TI EARLY DISEASE CHARACTERISTICS OF ENTHESITIS-RELATED ARTHRITIS REVEALS
ELEVATED TRANSFORMING GROWTH FACTOR-BETA
SO JOURNAL OF INVESTIGATIVE MEDICINE
LA English
DT Meeting Abstract
C1 [Srinivasalu, Hemalatha; Layh-Schmitt, Gerlinde; Ward, Michael M.; Colbert, Robert A.] NIAMS, NIH, Bethesda, MD USA.
[Srinivasalu, Hemalatha] Nemours Alfred I duPont Hosp Children, Wilmington, DE USA.
[Barnes, Michael G.] Cincinnati Childrens Hosp, Cincinnati BioBank, Cincinnati, OH USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1081-5589
J9 J INVEST MED
JI J. Invest. Med.
PD MAR
PY 2012
VL 60
IS 3
BP 621
EP 621
PG 1
WC Medicine, General & Internal; Medicine, Research & Experimental
SC General & Internal Medicine; Research & Experimental Medicine
GA 898YL
UT WOS:000300778200024
ER
PT J
AU Estrada-Veras, JI
Gahl, WA
Gochuico, B
AF Estrada-Veras, Juvianee I.
Gahl, William A.
Gochuico, Bernadette
TI ERDHEIM-CHESTER DISEASE (ECD): NATURAL HISTORY
SO JOURNAL OF INVESTIGATIVE MEDICINE
LA English
DT Meeting Abstract
C1 [Estrada-Veras, Juvianee I.; Gahl, William A.; Gochuico, Bernadette] NHGRI, NIH, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1081-5589
J9 J INVEST MED
JI J. Invest. Med.
PD MAR
PY 2012
VL 60
IS 3
BP 626
EP 626
PG 1
WC Medicine, General & Internal; Medicine, Research & Experimental
SC General & Internal Medicine; Research & Experimental Medicine
GA 898YL
UT WOS:000300778200041
ER
PT J
AU Zhang, JH
Chen, ZL
Fritz, JH
Rochman, Y
Leonard, WJ
Gommerman, JL
Plumb, AW
Abraham, N
Croy, BA
AF Zhang, Jianhong
Chen, Zhilin
Fritz, Joerg H.
Rochman, Yrina
Leonard, Warren J.
Gommerman, Jennifer L.
Plumb, Adam W.
Abraham, Ninan
Croy, B. Anne
TI Unusual timing of CD127 expression by mouse uterine natural killer cells
SO JOURNAL OF LEUKOCYTE BIOLOGY
LA English
DT Article
DE decidua; interleukin 7; stromal factor; thymic stromal lymphopoietin
ID THYMIC STROMAL LYMPHOPOIETIN; METRIAL GLAND-CELLS; NK CELLS;
MATERNAL/FETAL INTERFACE; INTERFERON-GAMMA; BONE-MARROW; PREGNANCY;
DIFFERENTIATION; MATURATION; AIRE
AB Decidualization, a progesterone-dependent process that alters endometrial stromal cells at implantation sites in humans and rodents, is accompanied by a highly regulated, NK cell-dominated leukocyte influx into decidual basalis (DB). Whether uNK cells differentiate from uterine progenitor cells is unknown, as are the mechanisms restricting leukocytes to DB. We asked if cells expressing the early NK lineage marker CD127 (IL-7R alpha)occurred in mouse decidua. CD127 was absent from gd6.5 decidual lymphoid cells but became expressed by a mature uNK cell subset in gd10.5 DB. DB and transient myometrial structures (MLAp) that ring maternal blood vessels supplying placentae expressed IL-7 and TSLP, the CD127 ligands, but with differing temporal and spatial patterns. UNK cells expressed TSLPR, and study of gd10.5 implantation sites from mice deleted for IL-7, CD127, or TSLPR suggested that IL-7 and its receptor have physiological roles in limiting expansion of immature uNK cells within MLAp, while the TSLP signaling pathway is used in DB to sustain IFN-gamma production from a subset of mature uNK cells. Regionalized, dynamic expression of the additional lymphoid organ stromal markers gp38/podoplanin and ER-TR7, but not CD157, were seen by immunohistochemistry in implantation sites, and DB and MLAp contained transcripts for Aire, a tolerance-promoting factor. These observations suggest that CD127(+) NK lineage progenitors are not present in the early postimplantation period of mouse uterus and that decidualized endometrial stroma has key immunoregulatory properties. J. Leukoc. Biol. 91: 417-426; 2012.
C1 [Zhang, Jianhong; Chen, Zhilin; Croy, B. Anne] Queens Univ, Dept Biomed & Mol Sci, Kingston, ON, Canada.
[Fritz, Joerg H.] McGill Univ, Dept Microbiol & Immunol, Complex Traits Grp, Montreal, PQ, Canada.
[Rochman, Yrina; Leonard, Warren J.] NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA.
[Gommerman, Jennifer L.] Univ Toronto, Dept Immunol, Toronto, ON M5S 1A1, Canada.
[Plumb, Adam W.; Abraham, Ninan] Univ British Columbia, Dept Microbiol & Immunol, Vancouver, BC V5Z 1M9, Canada.
[Abraham, Ninan] Univ British Columbia, Dept Zool, Cell Biol Grp, Vancouver, BC, Canada.
RP Zhang, JH (reprint author), Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Room 6-1025,25 Orde St, Toronto, ON M5T 3H7, Canada.
EM jhz.zhang@utoronto.ca
OI Abraham, Ninan/0000-0002-2747-1246
FU Natural Sciences and Engineering Research Council, Canada; Canadian
Institutes of Health Research; Canada and Canadian Institutes of Health
Research Canada [67157]; Canada Research Chairs Program; Province of
Ontario/Queen; National Heart, Lung, and Blood Institute, National
Institutes of Health
FX This study was supported by the Natural Sciences and Engineering
Research Council, Canada and Canadian Institutes of Health Research
(B.A.C.), the Canada and Canadian Institutes of Health Research Canada
(MOP#67157; J.H.F and J.L.G), the Canada Research Chairs Program
(B.A.C.), Province of Ontario/Queen's Postdoctoral Fellowship (J.Z.),
and the Intramural Research Program, National Heart, Lung, and Blood
Institute, National Institutes of Health (Y.R. and W.J.L). We thank Mr.
K. Hatta and Drs. G. N. Smith and C. Tayade (Queen's University) for
helpful discussions and Dr. C. Paige and Mr. S. Corfe (University of
Toronto) for provision of pregnant Il7-/- uteri.
NR 49
TC 12
Z9 12
U1 0
U2 2
PU FEDERATION AMER SOC EXP BIOL
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA
SN 0741-5400
J9 J LEUKOCYTE BIOL
JI J. Leukoc. Biol.
PD MAR
PY 2012
VL 91
IS 3
BP 417
EP 426
DI 10.1189/jlb.1011501
PG 10
WC Cell Biology; Hematology; Immunology
SC Cell Biology; Hematology; Immunology
GA 901BT
UT WOS:000300937400008
PM 22227963
ER
PT J
AU Zhao, G
Wang, JN
Xu, XZ
Jing, YY
Tu, L
Li, XG
Chen, C
Cianflone, K
Wang, PH
Dackor, RT
Zeldin, DC
Wang, DW
AF Zhao, Gang
Wang, Jianing
Xu, Xizhen
Jing, Yanyan
Tu, Ling
Li, Xuguang
Chen, Chen
Cianflone, Katherine
Wang, Peihua
Dackor, Ryan T.
Zeldin, Darryl C.
Wang, Dao Wen
TI Epoxyeicosatrienoic acids protect rat hearts against tumor necrosis
factor-alpha-induced injury
SO JOURNAL OF LIPID RESEARCH
LA English
DT Article
DE apoptosis; cytochrome P450; eicosanoids; heart; peroxisome
proliferator-activated receptors
ID EPOXYGENASE-DERIVED EICOSANOIDS; EPIDERMAL-GROWTH-FACTOR; NITRIC-OXIDE
SYNTHASE; ARACHIDONIC-ACID; ENDOTHELIAL-CELLS; SIGNALING PATHWAYS;
CARDIAC MYOCYTES; HYPERTENSIVE-RATS; INDUCED APOPTOSIS; K+ CHANNELS
AB Epoxyeicosatrienoic acids (EET), the primary arachidonic acid metabolites of cytochrome P450 2J (CYP2J) epoxygenases, possess potent vasodilatory, anti-inflammatory, antiapoptotic, and mitogenic effects. To date, little is known about the role of CYP2J2 and EETs in tumor necrosis factor (TNF)-alpha-induced cardiac injury. We utilized cell culture and in vivo models to examine the effects of exogenously applied EETs or CYP2J2 overexpression on TNF-alpha-induced cardiac apoptosis and cardiac dysfunction. In neonatal rat cardiomyocytes, TNF-alpha-induced apoptosis was markedly attenuated by EETs or CYP2J2 overexpression, leading to significantly improved cell survival. Further studies showed that TNF-alpha decreased expression of the antiapoptotic proteins Bcl-2 and Bcl-xL, decreased I kappa B alpha and PPAR gamma, and also inhibited PI3K-dependent Akt and EGFR signaling. Both EETs and CYP2J2 overexpression reversed the effects of TNF-alpha on these pathways. Furthermore, overexpression of CYP2J2 in rats prevented the decline in cardiac function that is normally observed in TNF-alpha challenged animals. These results demonstrate that EETs or CYP2J2 overexpression can prevent TNF-alpha-induced cardiac cell injury and cardiac dysfunction by inhibiting apoptosis, reducing inflammation, and enhancing PPAR gamma expression. Targeting the CYP2J2 epoxygenase pathway may represent a novel approach to mitigate cardiac injury in diseases such as heart failure, where increased TNF-alpha levels are known to occur.-Zhao, G., J. Wang, X. Xu, Y. Jing, L. Tu, X. Li, C. Chen, K. Cianflone, P. Wang, R. T. Dackor, D. C. Zeldin, and D. W. Wang. Epoxyeicosatrienoic acids protect rat hearts against tumor necrosis factor-alpha-induced injury. J. Lipid Res. 2012. 53: 456-466.
C1 [Zhao, Gang; Wang, Jianing; Xu, Xizhen; Jing, Yanyan; Tu, Ling; Li, Xuguang; Chen, Chen; Wang, Peihua; Wang, Dao Wen] Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Dept Internal Med, Wuhan 430030, Peoples R China.
[Zhao, Gang; Wang, Jianing; Xu, Xizhen; Jing, Yanyan; Tu, Ling; Li, Xuguang; Chen, Chen; Wang, Peihua; Wang, Dao Wen] Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Gene Therapy Ctr, Wuhan 430030, Peoples R China.
[Cianflone, Katherine; Wang, Dao Wen] Univ Laval, Ctr Rech, Inst Univ Cardiol & Pneumol Quebec, Quebec City, PQ G1V 4G5, Canada.
[Dackor, Ryan T.; Zeldin, Darryl C.] NIEHS, Div Intramural Res, NIH, Res Triangle Pk, NC 27709 USA.
RP Tu, L (reprint author), Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Dept Internal Med, Wuhan 430030, Peoples R China.
EM proftu@tom.com; dwwang@tjh.tjmu.edu.cn
FU National Natural Science Foundation of China [31130031, 30770882,
81070236, 3113031]; National Basic Research Program of China (973
Program) [2007CB512004]; National Institute of Environmental Health
Sciences, National Institutes of Health
FX This work was supported by National Natural Science Foundation of China
Grant Nos. 31130031, 30770882, 81070236 and 3113031; by National Basic
Research Program of China (973 Program) Grant No. 2007CB512004; and by
the Intramural Research Program of the National Institute of
Environmental Health Sciences, National Institutes of Health. Its
contents are solely the responsibility of the authors and do not
necessarily represent the official views of the National Institutes of
Health.
NR 46
TC 24
Z9 25
U1 0
U2 2
PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA
SN 0022-2275
J9 J LIPID RES
JI J. Lipid Res.
PD MAR
PY 2012
VL 53
IS 3
BP 456
EP 466
DI 10.1194/jlr.M017319
PG 11
WC Biochemistry & Molecular Biology
SC Biochemistry & Molecular Biology
GA 900IK
UT WOS:000300880200014
PM 22223859
ER
PT J
AU Vyas, NS
Shamsi, SA
Malhotra, AK
Aitchison, KJ
Kumari, V
AF Vyas, Nora S.
Shamsi, Syed A.
Malhotra, Anil K.
Aitchison, Katherine J.
Kumari, Veena
TI Can genetics inform the management of cognitive deficits in
schizophrenia?
SO JOURNAL OF PSYCHOPHARMACOLOGY
LA English
DT Review
DE Schizophrenia; BDNF; copy number variation; cognition; dopamine;
glutamate receptors; pharmacology; serotonin
ID PLACEBO-CONTROLLED TRIAL; RANDOMIZED CONTROLLED-TRIAL; EARLY-ONSET
SCHIZOPHRENIA; CARDIO-FACIAL SYNDROME; DONEPEZIL ADJUNCTIVE TREATMENT;
POSITRON-EMISSION-TOMOGRAPHY; BDNF VAL66MET POLYMORPHISM; ANTERIOR
CINGULATE CORTEX; VAL(108/158) MET GENOTYPE; RARE STRUCTURAL VARIANTS
AB There is no doubt that schizophrenia has a significant genetic component and a number of candidate genes have been identified for this debilitating disorder. Of note, several of these are implicated in cognition. Cognitive deficits constitute core symptoms of schizophrenia, and while current antipsychotic treatment strategies aim to help psychosis-related symptomatology, the cognitive symptom domain is largely inadequately treated. A number of other pharmacological approaches (e.g. using drugs that target specific neurotransmitter systems) have also been attempted for the amelioration of cognitive deficits in this population; however, these too have had limited success so far. Psychological interventions appear promising, though there has been speculation regarding whether or not these produce long-term functional improvements. Pharmacogenetic studies of the cognitive effects of currently available antipsychotics, although in relatively early stages, suggest that the treatment of cognitive deficits in schizophrenia may be advanced by focusing on genetic variants associated with specific cognitive dysfunctions in the general population and using this to match the most relevant pharmacological and/or psychological interventions with the genetic and cognitive profiles of the target population. Such a strategy would encourage bottom-up advances in drug development and provide a platform for individualised treatment of cognitive deficits in schizophrenia.
C1 [Vyas, Nora S.] NIMH, Child Psychiat Branch, NIH, Bethesda, MD 20892 USA.
[Vyas, Nora S.; Aitchison, Katherine J.] Kings Coll London, Inst Psychiat, MRC SGDP Ctr, London WC2R 2LS, England.
[Shamsi, Syed A.; Malhotra, Anil K.] Zucker Hillside Hosp, Div Psychiat Res, N Shore Long Isl Jewish Hlth Syst, Glen Oaks, NY USA.
[Aitchison, Katherine J.] Univ Alberta, Dept Psychiat, Edmonton, AB, Canada.
[Kumari, Veena] Kings Coll London, Inst Psychiat, Dept Psychol, London WC2R 2LS, England.
[Kumari, Veena] S London & Maudsley NHS Fdn Trust, NIHR Biomed Res Ctr Mental Hlth, London, England.
RP Vyas, NS (reprint author), NIMH, Child Psychiat Branch, NIH, Bldg 10,Ctr Dr, Bethesda, MD 20892 USA.
EM nora.vyas@nih.gov
RI Aitchison, Katherine/G-4476-2013
OI Aitchison, Katherine/0000-0002-1107-3024
FU Fulbright Distinguished Scholar Award; US-UK Fulbright Commission
FX Dr Nora S Vyas is supported by the Fulbright Distinguished Scholar Award
by the US-UK Fulbright Commission.
NR 279
TC 6
Z9 6
U1 3
U2 13
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 0269-8811
J9 J PSYCHOPHARMACOL
JI J. Psychopharmacol.
PD MAR
PY 2012
VL 26
IS 3
SI SI
BP 334
EP 348
DI 10.1177/0269881111434623
PG 15
WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 900HE
UT WOS:000300876800002
PM 22328662
ER
PT J
AU Cutler, JA
Rush, AJ
McMahon, FJ
Laje, G
AF Cutler, Jessica A.
Rush, A. John
McMahon, Francis J.
Laje, Gonzalo
TI Common genetic variation in the indoleamine-2,3-dioxygenase genes and
antidepressant treatment outcome in major depressive disorder
SO JOURNAL OF PSYCHOPHARMACOLOGY
LA English
DT Article
DE Pharmacogenetics; depressive disorder; treatment outcome;
indoleamine-pyrrole 2, 3-dioxygenase; ID0; ID01; ID02
ID STAR-ASTERISK-D; ALPHA-INDUCED DEPRESSION; REPORT QIDS-SR; PSYCHOMETRIC
EVALUATION; QUICK INVENTORY; TRYPTOPHAN; ASSOCIATION; RECEPTOR;
SYMPTOMATOLOGY; NEUROTOXICITY
AB The essential amino acid tryptophan is the precursor to serotonin, but it can also be metabolized into kynurenine through indoleamine-2,3-dioxygenase (ID0). Increased immune activation has long been associated with symptoms of depression and has been shown to upregulate the expression of ID0. The presence of additional ID0 directs more tryptophan down the kynurenine pathway, leaving less available for synthesis of serotonin and its metabolites. Kynurenine can be metabolized through a series of enzymes to quinolinic acid, a potent N-methyl-D-aspartate receptor agonist with demonstrated neurotoxic effects. We tested the hypothesis that ID0 plays a role in outcome of treatment with the selective serotonin reuptake inhibitor, citalopram. Patients consisted of 1953 participants enrolled in the Sequenced Treatment Alternatives to Relieve Depression study (STAR*D). Genotypes corresponding to 94 single nucleotide polymorphisms (SNPs) in the genes ID01 and ID02, which encode ID0 and ID02, were extracted from a larger genome-wide set and analyzed using single marker tests to look for association with previously defined response, remission and QIDS-C score change phenotypes, with adequate correction for racial stratification and multiple testing. One SNP, rs2929115, showed evidence of association with citalopram response (OR = 0.64, p = 0.0005) after experiment-wide correction for multiple testing. Another closely associated marker, rs2929116 (OR = 0.64, p = 0.0006) had an experiment-wide significant result. Both implicated SNPs are located between 26 kb and 28 kb downstream of ID02. We conclude that common genetic variation in ID01 and ID02 may play a role in antidepressant treatment outcome. These results are modest in a genome-wide context and need to be replicated in an independent sample.
C1 [Cutler, Jessica A.; McMahon, Francis J.; Laje, Gonzalo] NIMH, Genet Basis Mood & Anxiety Disorders Unit, Bethesda, MD 20892 USA.
[Rush, A. John] Duke Natl Univ, Singapore, Singapore.
RP Laje, G (reprint author), NIMH, Genet Basis Mood & Anxiety Disorders Sect, 35 Convent Dr,Rm 1A207, Bethesda, MD 20892 USA.
EM gonzalo.laje@nih.gov
RI Laje, Gonzalo/L-2654-2014;
OI Laje, Gonzalo/0000-0003-2763-3329; McMahon, Francis/0000-0002-9469-305X;
Rush, Augustus/0000-0003-2004-2382
FU National Institute of Mental Health, NIH [N01MH90003]; NARSAD; Advanced
Neuromodulation Systems, Inc.; AstraZenica; Best Practice Project
Management, Inc.; Cyberonics Inc.; Eli Lilly Company; Forest
Pharmaceuticals Inc.; Gerson Lehman Group; GlaxoSmithKline; Healthcare
Technology Systems Inc.; Jazz Pharmaceuticals; Magellan Health Services;
Merck Co. Inc.; National Institute of Mental Health; Neuronetics; Ono
Pharmaceutical; Organon USA Inc.; Otsuka; Pamlab; Personality Disorder
Research Corporation; Pfizer Inc.; Robert Wood Johnson Foundation;
Stanley Medical Research Institute; Urban Institute; Wyeth-Ayerst
Laboratories Inc.; Guilford Publications and Healthcare Technology
Systems Inc.; UT Southwestern Medical Center; [K99MH085098-01]
FX This study was funded by the Intramural Research Program of the National
Institute of Mental Health, NIH, by a NARSAD Independent Investigator
Award to Francis McMahon and by K99MH085098-01 to Gonzalo Laje. The
authors thank the STAR*D research team for acquisition of clinical data
and DNA samples. Data and sample collection were funded with federal
funds from the NIMH, NIH, under contract N01MH90003 to University of
Texas Southwestern Medical Center at Dallas (Principal investigator, A
John Rush).; Ms Cutler, Dr Laje and Dr McMahon report no competing
interests. Dr Rush has served as an advisor, consultant, or speaker for
or received research support from Advanced Neuromodulation Systems,
Inc.; AstraZenica; Best Practice Project Management, Inc.;
Bristol-Meyers Squibb Company; Cyberonics Inc.; Eli Lilly & Company;
Forest Pharmaceuticals Inc.; Gerson Lehman Group; GlaxoSmithKline;
Healthcare Technology Systems Inc.; Jazz Pharmaceuticals; Magellan
Health Services; Merck & Co. Inc.; the National Institute of Mental
Health; Neuronetics; Ono Pharmaceutical; Organon USA Inc.; Otsuka;
Pamlab; Personality Disorder Research Corporation; Pfizer Inc.; the
Robert Wood Johnson Foundation; the Stanley Medical Research Institute;
the Urban Institute; and Wyeth-Ayerst Laboratories Inc. Dr Rush has
equity holdings in Pfizer Inc., and receives royalty/patent income from
Guilford Publications and Healthcare Technology Systems Inc., and UT
Southwestern Medical Center.
NR 27
TC 19
Z9 19
U1 1
U2 6
PU SAGE PUBLICATIONS LTD
PI LONDON
PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND
SN 0269-8811
J9 J PSYCHOPHARMACOL
JI J. Psychopharmacol.
PD MAR
PY 2012
VL 26
IS 3
SI SI
BP 360
EP 367
DI 10.1177/0269881111434622
PG 8
WC Clinical Neurology; Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 900HE
UT WOS:000300876800004
PM 22282879
ER
PT J
AU Morgan, AA
Pyrgos, VJ
Nadeau, KC
Williamson, PR
Butte, AJ
AF Morgan, Alexander A.
Pyrgos, Vasilios J.
Nadeau, Kari C.
Williamson, Peter R.
Butte, Atul Janardhan
TI Multiplex meta-analysis of RNA expression to identify genes with
variants associated with immune dysfunction
SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION
LA English
DT Article
ID CD8(+) T-CELLS; MISSING HERITABILITY; COMPLEX DISEASES; WINNERS CURSE;
GENOME; TRANSCRIPTION; IDENTIFICATION; MUTATIONS; RESPONSES; PROFILES
AB Objective We demonstrate a genome-wide method for the integration of many studies of gene expression of phenotypically similar disease processes, a method of multiplex meta-analysis. We use immune dysfunction as an example disease process.
Design We use a heterogeneous collection of datasets across human and mice samples from a range of tissues and different forms of immunodeficiency. We developed a method integrating Tibshirani's modified t-test (SAM) is used to interrogate differential expression within a study and Fisher's method for omnibus meta-analysis to identify differentially expressed genes across studies. The ability of this overall gene expression profile to prioritize disease associated genes is evaluated by comparing against the results of a recent genome wide association study for common variable immunodeficiency (CVID).
Results Our approach is able to prioritize genes associated with immunodeficiency in general (area under the ROC curve = 0.713) and CVID in particular (area under the ROC curve - 0.643).
Conclusions This approach may be used to investigate a larger range of failures of the immune system. Our method may be extended to other disease processes, using RNA levels to prioritize genes likely to contain disease associated DNA variants.
C1 [Morgan, Alexander A.; Butte, Atul Janardhan] Stanford Univ, Dept Pediat, Div Syst Med, Stanford, CA 94305 USA.
[Morgan, Alexander A.; Butte, Atul Janardhan] Stanford Univ, Biomed Informat Grad Training Program, Stanford, CA 94305 USA.
[Pyrgos, Vasilios J.; Williamson, Peter R.] NIAID, Lab Clin Infect Dis, Bethesda, MD 20892 USA.
[Nadeau, Kari C.] Stanford Univ, Div Immunol, Dept Pediat, Stanford, CA 94305 USA.
RP Butte, AJ (reprint author), Stanford Univ, Dept Pediat, Div Syst Med, 1265 Welch Rd X-163,MS-5415, Stanford, CA 94305 USA.
EM abutte@stanford.edu
FU March of Dimes; Lucile Packard Foundation for Children's Health; Hewlett
Packard Foundation; National Library of Medicine [R01 LM009719];
Biomedical Informatics training grant [T15 LM007033]; NIH, NIAID
FX This work was supported in part by the March of Dimes, the Lucile
Packard Foundation for Children's Health, the Hewlett Packard
Foundation, and the National Library of Medicine through direct research
funding (R01 LM009719) and a Biomedical Informatics training grant (T15
LM007033). This research was also supported, in part, by the Intramural
Research Program of the NIH, NIAID.
NR 49
TC 2
Z9 2
U1 0
U2 7
PU B M J PUBLISHING GROUP
PI LONDON
PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND
SN 1067-5027
J9 J AM MED INFORM ASSN
JI J. Am. Med. Inf. Assoc.
PD MAR
PY 2012
VL 19
IS 2
BP 284
EP 288
DI 10.1136/amiajnl-2011-000657
PG 5
WC Computer Science, Information Systems; Computer Science,
Interdisciplinary Applications; Health Care Sciences & Services;
Information Science & Library Science; Medical Informatics
SC Computer Science; Health Care Sciences & Services; Information Science &
Library Science; Medical Informatics
GA 898UP
UT WOS:000300768100023
PM 22319178
ER
PT J
AU Gipson, C
Brown, P
AF Gipson, Chester
Brown, Patricia
TI A word from USDA and OLAW
SO LAB ANIMAL
LA English
DT Editorial Material
C1 [Gipson, Chester] USDA, APHIS, AC, Washington, DC 20250 USA.
[Brown, Patricia] NIH, OLAW, OER, OD,HHS, Bethesda, MD 20892 USA.
RP Gipson, C (reprint author), USDA, APHIS, AC, Washington, DC 20250 USA.
NR 3
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
J9 LAB ANIMAL
JI Lab Anim.
PD MAR
PY 2012
VL 41
IS 3
BP 64
EP 64
PG 1
WC Veterinary Sciences
SC Veterinary Sciences
GA 902BW
UT WOS:000301014600015
PM 22343456
ER
PT J
AU Yi, J
Wu, XFS
Crites, T
Hammer, JA
AF Yi, Jason
Wu, Xufeng S.
Crites, Travis
Hammer, John A., III
TI Actin retrograde flow and actomyosin II arc contraction drive receptor
cluster dynamics at the immunological synapse in Jurkat T cells
SO MOLECULAR BIOLOGY OF THE CELL
LA English
DT Article
ID SUPRAMOLECULAR ACTIVATION CLUSTER; NEURONAL GROWTH CONES; MYOSIN-II;
ADHESION MOLECULES; FUSION PROTEIN; FISSION YEAST; MICROCLUSTERS;
CYTOSKELETON; RECRUITMENT; MIGRATION
AB Actin retrograde flow and actomyosin II contraction have both been implicated in the inward movement of T cell receptor (TCR) microclusters and immunological synapse formation, but no study has integrated and quantified their relative contributions. Using Jurkat T cells expressing fluorescent myosin IIA heavy chain and F-tractin-a novel reporter for F-actin-we now provide direct evidence that the distal supramolecular activation cluster (dSMAC) and peripheral supramolecular activation cluster (pSMAC) correspond to lamellipodial (LP) and lamellar (LM) actin networks, respectively, as hypothesized previously. Our images reveal concentric and contracting actomyosin II arcs/rings at the LM/pSMAC. Moreover, the speeds of centripetally moving TCR microclusters correspond very closely to the rates of actin retrograde flow in the LP/dSMAC and actomyosin II arc contraction in the LM/pSMAC. Using cytochalasin D and jasplakinolide to selectively inhibit actin retrograde flow in the LP/dSMAC and b.lebbistatin to selectively inhibit actomyosin II arc contraction in the LM/pSMAC, we demonstrate that both forces are required for centripetal TCR microcluster transport. Finally, we show that leukocyte function-associated antigen 1 clusters accumulate over time at the inner aspect of the LM/pSMAC and that this accumulation depends on actomyosin II contraction. Thus actin retrograde flow and actomyosin II arc contraction coordinately drive receptor cluster dynamics at the immunological synapse.
C1 [Yi, Jason; Wu, Xufeng S.; Hammer, John A., III] NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA.
[Yi, Jason] Univ N Carolina, Dept Biol, Chapel Hill, NC 27599 USA.
[Crites, Travis] NIAID, Lab Cellular & Mol Immunol, NIH, Bethesda, MD 20892 USA.
RP Hammer, JA (reprint author), NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA.
EM hammerj@nhlbi.nih.gov
NR 52
TC 76
Z9 76
U1 1
U2 5
PU AMER SOC CELL BIOLOGY
PI BETHESDA
PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA
SN 1059-1524
J9 MOL BIOL CELL
JI Mol. Biol. Cell
PD MAR 1
PY 2012
VL 23
IS 5
BP 834
EP 852
DI 10.1091/mbc.E11-08-0731
PG 19
WC Cell Biology
SC Cell Biology
GA 901BN
UT WOS:000300936800010
PM 22219382
ER
PT J
AU Wu, TL
Topfer, K
Lin, SW
Li, H
Bian, A
Zhou, XY
High, KA
Ertl, HCJ
AF Wu, TeLang
Toepfer, Katrin
Lin, Shih-Wen
Li, Hua
Bian, Ang
Zhou, Xiang Y.
High, Katherine A.
Ertl, Hildegund C. J.
TI Self-complementary AAVs Induce More Potent Transgene Product-specific
Immune Responses Compared to a Single-stranded Genome
SO MOLECULAR THERAPY
LA English
DT Article
ID ADENOASSOCIATED VIRUS VECTORS; EFFICIENT TRANSDUCTION; GENE-THERAPY;
MUSCULAR-DYSTROPHY; FACTOR-IX; EXPRESSION; LIVER; HEMOPHILIA; CELLS;
ACTIVATION
AB Using a mouse model we show that self-complementary (sc) adeno-associated virus (AAV) vectors pseudotyped with capsids of serotypes 2, 7 or 8 induce more potent transgene product-specific CD8(+) T cell and antibody responses compared to corresponding single-stranded (ss) AAV vectors. These data suggest that the higher and more rapidly appearing amounts of transgene product achieved with scAAV vectors may increase detrimental immune responses in gene transfer recipients. Received 22 March 2011; accepted 21 November 2011; published online 20 December 2011. doi:10.1038/mt.2011.280
C1 [Wu, TeLang; Toepfer, Katrin; Lin, Shih-Wen; Li, Hua; Bian, Ang; Zhou, Xiang Y.; Ertl, Hildegund C. J.] Wistar Inst Anat & Biol, Philadelphia, PA 19104 USA.
[Wu, TeLang] Univ Penn, Sch Med, Philadelphia, PA 19104 USA.
[Toepfer, Katrin] German Primate Ctr, Unit Infect Models, Gottingen, Germany.
[Lin, Shih-Wen] NCI, NIH, Bethesda, MD 20892 USA.
[High, Katherine A.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA.
[High, Katherine A.] Howard Hughes Med Inst, Chevy Chase, MD USA.
RP Ertl, HCJ (reprint author), Wistar Inst Anat & Biol, 3601 Spruce St, Philadelphia, PA 19104 USA.
EM ertl@wistar.upenn.edu
FU NHLBL [P01 HL078810]
FX This work was supported by a grant from NHLBL (P01 HL078810). We wish to
thank Ms Cole for assistance in preparing the figures and the
manuscript. The authors declared no conflict of interest.
NR 31
TC 13
Z9 14
U1 0
U2 3
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
J9 MOL THER
JI Mol. Ther.
PD MAR
PY 2012
VL 20
IS 3
BP 572
EP 579
DI 10.1038/mt.2011.280
PG 8
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 901EE
UT WOS:000300943700011
PM 22186792
ER
PT J
AU Bish, LT
Sleeper, MM
Forbes, SC
Wang, BJ
Reynolds, C
Singletary, GE
Trafny, D
Morine, KJ
Sanmiguel, J
Cecchini, S
Virag, T
Vulin, A
Beley, C
Bogan, J
Wilson, JM
Vandenborne, K
Kornegay, JN
Walter, GA
Kotin, RM
Garcia, L
Sweeney, HL
AF Bish, Lawrence T.
Sleeper, Meg M.
Forbes, Sean C.
Wang, Bingjing
Reynolds, Caryn
Singletary, Gretchen E.
Trafny, Dennis
Morine, Kevin J.
Sanmiguel, Julio
Cecchini, Sylvain
Virag, Tamas
Vulin, Adeline
Beley, Cyriaque
Bogan, Janet
Wilson, James M.
Vandenborne, Krista
Kornegay, Joe N.
Walter, Glenn A.
Kotin, Robert M.
Garcia, Luis
Sweeney, H. Lee
TI Long-term Restoration of Cardiac Dystrophin Expression in Golden
Retriever Muscular Dystrophy Following rAAV6-mediated Exon Skipping
SO MOLECULAR THERAPY
LA English
DT Article
ID PERCUTANEOUS TRANSENDOCARDIAL DELIVERY; CONJUGATED MORPHOLINO OLIGOMERS;
ADENOASSOCIATED VIRUS 6; GENE-THERAPY; DUCHENNES CARDIOMYOPATHY;
SKELETAL-MUSCLES; CANINE MODEL; MDX MICE; DMD; STRAIN
AB Although restoration of dystrophin expression via exon skipping in both cardiac and skeletal muscle has been successfully demonstrated in the mdx mouse, restoration of cardiac dystrophin expression in large animal models of Duchenne muscular dystrophy (DMD) has proven to be a challenge. In large animals, investigators have focused on using intravenous injection of antisense oligonucleotides (AO) to mediate exon skipping. In this study, we sought to optimize restoration of cardiac dystrophin expression in the golden retriever muscular dystrophy (GRMD) model using percutaneous transendocardial delivery of recombinant AAV6 (rAAV6) to deliver a modified U7 small nuclear RNA (snRNA) carrying antisense sequence to target the exon splicing enhancers of exons 6 and 8 and correct the disrupted reading frame. We demonstrate restoration of cardiac dystrophin expression at 13 months confirmed by reverse transcription-PCR (RT-PCR) and immunoblot as well as membrane localization by immunohistochemistry. This was accompanied by improved cardiac function as assessed by cardiac magnetic resonance imaging (MRI). Percutaneous transendocardial delivery of rAAV6 expressing a modified U7 exon skipping construct is a safe, effective method for restoration of dystrophin expression and improvement of cardiac function in the GRMD canine and may be easily translatable to human DMD patients. Received 24 May 2011; accepted 9 November 2011; published online 6 December 2011. doi:10.1038/mt.2011.264
C1 [Bish, Lawrence T.; Wang, Bingjing; Morine, Kevin J.; Sweeney, H. Lee] Univ Penn, Sch Med, Dept Physiol, Philadelphia, PA 19104 USA.
[Sleeper, Meg M.; Reynolds, Caryn; Singletary, Gretchen E.; Trafny, Dennis] Univ Penn, Cardiol Sect, Dept Clin Studies, Vet Hosp, Philadelphia, PA 19104 USA.
[Forbes, Sean C.; Vandenborne, Krista] Univ Florida, Dept Phys Therapy, Gainesville, FL USA.
[Sanmiguel, Julio; Wilson, James M.] Univ Penn, Sch Med, Div Med Genet, Gene Therapy Program, Philadelphia, PA 19104 USA.
[Cecchini, Sylvain; Virag, Tamas; Kotin, Robert M.] NHLBI, Mol Virol & Gene Delivery Sect, Lab Biochem Genet, NIH, Bethesda, MD 20892 USA.
[Vulin, Adeline; Beley, Cyriaque; Garcia, Luis] CNRS UMR7215, Inst Myol, UPMC Um76, Inserm U974, Paris, France.
[Bogan, Janet; Kornegay, Joe N.] Univ N Carolina, Dept Pathol & Lab Med, Chapel Hill, NC USA.
[Bogan, Janet; Kornegay, Joe N.] Univ N Carolina, Dept Neurol, Chapel Hill, NC USA.
[Bogan, Janet; Kornegay, Joe N.] Univ N Carolina, Gene Therapy Ctr, Chapel Hill, NC USA.
[Walter, Glenn A.] Univ Florida, Dept Physiol & Funct Genom, Gainesville, FL USA.
RP Bish, LT (reprint author), B400 Richards Bldg,3700 Hamilton Walk, Philadelphia, PA 19104 USA.
EM bish@mail.med.upenn.edu
RI Wilson, James/F-9220-2011
OI Wilson, James/0000-0002-9630-3131
FU NHLBI [P01-HL059407]; Parent Project Muscular Dystrophy; Wellstone
Muscular Dystrophy Cooperative Center [U54-AR052646]; NIH
[T32-HL-007748, RR02512]; International Collaborative Effort (ICE) for
DMD; Division of Intramural Research of National Heart, Lung, and Blood
Institute (NIH); University of Pennsylvania
FX This work was supported by a grant from the NHLBI (P01-HL059407) (to H.
L. S. and J. M. W.), from the Parent Project Muscular Dystrophy (to H.
L. S.), by a Wellstone Muscular Dystrophy Cooperative Center Grant
(U54-AR052646) (to H. L. S.), by NIH (T32-HL-007748) (to L. T. B.) and
(RR02512) (to Mark Haskins), and by the International Collaborative
Effort (ICE) for DMD (to H. L. S., R. M. K., and L. G.). Support was
also provided by the Division of Intramural Research of the National
Heart, Lung, and Blood Institute (NIH) (R. M. K.). We thank the Vector
Core of the Children's Hospital of Philadelphia and Katherine High, MD
for vector production. We thank Mark Haskins, VMD, PhD (University of
Pennsylvania) for support of the canine colony. J. M. W. is an inventor
on patents that have been licensed to various biopharmaceutical
companies. Portions of the technology described in this report are
covered by United States and European patents assigned to the Secretary
of the Department of Health and Human Services. A fraction of the
licensing fees and royalty payments made to the NIH are distributed to
the inventors in accordance with US Government and NIH policy.
NR 49
TC 35
Z9 35
U1 1
U2 11
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1525-0016
J9 MOL THER
JI Mol. Ther.
PD MAR
PY 2012
VL 20
IS 3
BP 580
EP 589
DI 10.1038/mt.2011.264
PG 10
WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine,
Research & Experimental
SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research &
Experimental Medicine
GA 901EE
UT WOS:000300943700012
PM 22146342
ER
PT J
AU Savage, SA
AF Savage, Sharon A.
TI Connecting complex disorders through biology
SO NATURE GENETICS
LA English
DT Editorial Material
ID DYSKERATOSIS-CONGENITA; TELOMERE BIOLOGY; COMPONENT; MICROANGIOPATHY;
CALCIFICATIONS; MUTATIONS; DISEASE; LENGTH; CYSTS
AB Mutations in CTC1, which encodes a key telomere component, have been identified as the cause of Coats plus syndrome. This discovery provides an important pathophysiological link between Coats plus and the clinically related telomere disorders dyskeratosis congenita, Revesz syndrome and Hoyeraal-Hreidarsson syndrome.
C1 NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA.
RP Savage, SA (reprint author), NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, NIH, Rockville, MD USA.
EM savagesh@mail.nih.gov
RI Savage, Sharon/B-9747-2015
OI Savage, Sharon/0000-0001-6006-0740
NR 16
TC 12
Z9 13
U1 0
U2 2
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1061-4036
J9 NAT GENET
JI Nature Genet.
PD MAR
PY 2012
VL 44
IS 3
BP 238
EP 240
DI 10.1038/ng.2206
PG 4
WC Genetics & Heredity
SC Genetics & Heredity
GA 899VC
UT WOS:000300843600004
PM 22366859
ER
PT J
AU Stolk, L
Perry, JRB
Chasman, DI
He, CY
Mangino, M
Sulem, P
Barbalic, M
Broer, L
Byrne, EM
Ernst, F
Esko, T
Franceschini, N
Gudbjartsson, DF
Hottenga, JJ
Kraft, P
McArdle, PF
Porcu, E
Shin, SY
Smith, AV
van Wingerden, S
Zhai, G
Zhuang, WV
Albrecht, E
Alizadeh, BZ
Aspelund, T
Bandinelli, S
Lauc, LB
Beckmann, JS
Boban, M
Boerwinkle, E
Broekmans, FJ
Burri, A
Campbell, H
Chanock, SJ
Chen, C
Cornelis, MC
Corre, T
Coviello, AD
d'Adamo, P
Davies, G
de Faire, U
de Geus, EJC
Deary, IJ
Dedoussis, GVZ
Deloukas, P
Ebrahim, S
Eiriksdottir, G
Emilsson, V
Eriksson, JG
Fauser, BCJM
Ferreli, L
Ferrucci, L
Fischer, K
Folsom, AR
Garcia, ME
Gasparini, P
Gieger, C
Glazer, N
Grobbee, DE
Hall, P
Haller, T
Hankinson, SE
Hass, M
Hayward, C
Heath, AC
Hofman, A
Ingelsson, E
Janssens, ACJW
Johnson, AD
Karasik, D
Kardia, SLR
Keyzer, J
Kiel, DP
Kolcic, I
Kutalik, Z
Lahti, J
Lai, S
Laisk, T
Laven, JSE
Lawlor, DA
Liu, JJ
Lopez, LM
Louwers, YV
Magnusson, PKE
Marongiu, M
Martin, NG
Klaric, IM
Masciullo, C
McKnight, B
Medland, SE
Melzer, D
Mooser, V
Navarro, P
Newman, AB
Nyholt, DR
Onland-Moret, NC
Palotie, A
Pare, G
Parker, AN
Pedersen, NL
Peeters, PHM
Pistis, G
Plump, AS
Polasek, O
Pop, VJM
Psaty, BM
Raikkonen, K
Rehnberg, E
Rotter, JI
Rudan, I
Sala, C
Salumets, A
Scuteri, A
Singleton, A
Smith, JA
Snieder, H
Soranzo, N
Stacey, SN
Starr, JM
Stathopoulou, MG
Stirrups, K
Stolk, RP
Styrkarsdottir, U
Sun, YV
Tenesa, A
Thorand, B
Toniolo, D
Tryggvadottir, L
Tsui, K
Ulivi, S
van Dam, RM
van der Schouw, YT
van Gils, CH
van Nierop, P
Vink, JM
Visscher, PM
Voorhuis, M
Waeber, G
Wallaschofski, H
Wichmann, HE
Widen, E
Wijnands-van Gent, CJM
Willemsen, G
Wilson, JF
Wolffenbuttel, BHR
Wright, AF
Yerges-Armstrong, LM
Zemunik, T
Zgaga, L
Zillikens, MC
Zygmunt, M
Arnold, AM
Boomsma, DI
Buring, JE
Crisponi, L
Demerath, EW
Gudnason, V
Harris, TB
Hu, FB
Hunter, DJ
Launer, LJ
Metspalu, A
Montgomery, GW
Oostra, BA
Ridker, PM
Sanna, S
Schlessinger, D
Spector, TD
Stefansson, K
Streeten, EA
Thorsteinsdottir, U
Uda, M
Uitterlinden, AG
van Duijn, CM
Volzke, H
Murray, A
Murabito, JM
Visser, JA
Lunetta, KL
AF Stolk, Lisette
Perry, John R. B.
Chasman, Daniel I.
He, Chunyan
Mangino, Massimo
Sulem, Patrick
Barbalic, Maja
Broer, Linda
Byrne, Enda M.
Ernst, Florian
Esko, Tonu
Franceschini, Nora
Gudbjartsson, Daniel F.
Hottenga, Jouke-Jan
Kraft, Peter
McArdle, Patrick F.
Porcu, Eleonora
Shin, So-Youn
Smith, Albert V.
van Wingerden, Sophie
Zhai, Guangju
Zhuang, Wei V.
Albrecht, Eva
Alizadeh, Behrooz Z.
Aspelund, Thor
Bandinelli, Stefania
Lauc, Lovorka Barac
Beckmann, Jacques S.
Boban, Mladen
Boerwinkle, Eric
Broekmans, Frank J.
Burri, Andrea
Campbell, Harry
Chanock, Stephen J.
Chen, Constance
Cornelis, Marilyn C.
Corre, Tanguy
Coviello, Andrea D.
d'Adamo, Pio
Davies, Gail
de Faire, Ulf
de Geus, Eco J. C.
Deary, Ian J.
Dedoussis, George V. Z.
Deloukas, Panagiotis
Ebrahim, Shah
Eiriksdottir, Gudny
Emilsson, Valur
Eriksson, Johan G.
Fauser, Bart C. J. M.
Ferreli, Liana
Ferrucci, Luigi
Fischer, Krista
Folsom, Aaron R.
Garcia, Melissa E.
Gasparini, Paolo
Gieger, Christian
Glazer, Nicole
Grobbee, Diederick E.
Hall, Per
Haller, Toomas
Hankinson, Susan E.
Hass, Merli
Hayward, Caroline
Heath, Andrew C.
Hofman, Albert
Ingelsson, Erik
Janssens, A. Cecile J. W.
Johnson, Andrew D.
Karasik, David
Kardia, Sharon L. R.
Keyzer, Jules
Kiel, Douglas P.
Kolcic, Ivana
Kutalik, Zoltan
Lahti, Jari
Lai, Sandra
Laisk, Triin
Laven, Joop S. E.
Lawlor, Debbie A.
Liu, Jianjun
Lopez, Lorna M.
Louwers, Yvonne V.
Magnusson, Patrik K. E.
Marongiu, Mara
Martin, Nicholas G.
Klaric, Irena Martinovic
Masciullo, Corrado
McKnight, Barbara
Medland, Sarah E.
Melzer, David
Mooser, Vincent
Navarro, Pau
Newman, Anne B.
Nyholt, Dale R.
Onland-Moret, N. Charlotte
Palotie, Aarno
Pare, Guillaume
Parker, Alex N.
Pedersen, Nancy L.
Peeters, Petra H. M.
Pistis, Giorgio
Plump, Andrew S.
Polasek, Ozren
Pop, Victor J. M.
Psaty, Bruce M.
Raikkonen, Katri
Rehnberg, Emil
Rotter, Jerome I.
Rudan, Igor
Sala, Cinzia
Salumets, Andres
Scuteri, Angelo
Singleton, Andrew
Smith, Jennifer A.
Snieder, Harold
Soranzo, Nicole
Stacey, Simon N.
Starr, John M.
Stathopoulou, Maria G.
Stirrups, Kathleen
Stolk, Ronald P.
Styrkarsdottir, Unnur
Sun, Yan V.
Tenesa, Albert
Thorand, Barbara
Toniolo, Daniela
Tryggvadottir, Laufey
Tsui, Kim
Ulivi, Sheila
van Dam, Rob M.
van der Schouw, Yvonne T.
van Gils, Carla H.
van Nierop, Peter
Vink, Jacqueline M.
Visscher, Peter M.
Voorhuis, Marlies
Waeber, Gerard
Wallaschofski, Henri
Wichmann, H. Erich
Widen, Elisabeth
Wijnands-van Gent, Colette J. M.
Willemsen, Gonneke
Wilson, James F.
Wolffenbuttel, Bruce H. R.
Wright, Alan F.
Yerges-Armstrong, Laura M.
Zemunik, Tatijana
Zgaga, Lina
Zillikens, M. Carola
Zygmunt, Marek
Arnold, Alice M.
Boomsma, Dorret I.
Buring, Julie E.
Crisponi, Laura
Demerath, Ellen W.
Gudnason, Vilmundur
Harris, Tamara B.
Hu, Frank B.
Hunter, David J.
Launer, Lenore J.
Metspalu, Andres
Montgomery, Grant W.
Oostra, Ben A.
Ridker, Paul M.
Sanna, Serena
Schlessinger, David
Spector, Tim D.
Stefansson, Kari
Streeten, Elizabeth A.
Thorsteinsdottir, Unnur
Uda, Manuela
Uitterlinden, Andre G.
van Duijn, Cornelia M.
Voelzke, Henry
Murray, Anna
Murabito, Joanne M.
Visser, Jenny A.
Lunetta, Kathryn L.
CA LifeLines Cohort Study
TI Meta-analyses identify 13 loci associated with age at menopause and
highlight DNA repair and immune pathways
SO NATURE GENETICS
LA English
DT Article
ID PREMATURE OVARIAN FAILURE; FOLLICLE-STIMULATING-HORMONE; GENOME-WIDE
ASSOCIATION; GENE-EXPRESSION; NATURAL MENOPAUSE; PROTEIN; DISEASE;
POLYMORPHISMS; ONSET; MUTATION
AB To newly identify loci for age at natural menopause, we carried out a meta-analysis of 22 genome-wide association studies (GWAS) in 38,968 women of European descent, with replication in up to 14,435 women. In addition to four known loci, we identified 13 loci newly associated with age at natural menopause (at P < 5 x 10(-8)). Candidate genes located at these newly associated loci include genes implicated in DNA repair (EXO1, HELQ, UIMC1, FAM175A, FANCI, TLK1, POLG and PRIM1) and immune function (IL11, NLRP11 and PRRC2A (also known as BAT2)). Gene-set enrichment pathway analyses using the full GWAS data set identified exoDNase, NF-kappa B signaling and mitochondrial dysfunction as biological processes related to timing of menopause.
C1 [Perry, John R. B.; Melzer, David; Murray, Anna] Univ Exeter, Peninsula Med Sch, Exeter, Devon, England.
[Stolk, Lisette; Zillikens, M. Carola; Uitterlinden, Andre G.; Visser, Jenny A.] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands.
[Stolk, Lisette; Uitterlinden, Andre G.; van Duijn, Cornelia M.] Netherlands Consortium Hlth Aging, Rotterdam, Netherlands.
[Perry, John R. B.] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.
[Chasman, Daniel I.; Pare, Guillaume; Buring, Julie E.; Ridker, Paul M.] Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA.
[Chasman, Daniel I.; Pare, Guillaume; Buring, Julie E.; Ridker, Paul M.] Harvard Univ, Sch Med, Boston, MA USA.
[He, Chunyan] Indiana Univ Sch Med, Dept Publ Hlth, Indianapolis, IN USA.
[He, Chunyan] Indiana Univ, Melvin & Bren Simon Canc Ctr, Indianapolis, IN 46204 USA.
[Mangino, Massimo; Zhai, Guangju; Burri, Andrea; Soranzo, Nicole; Spector, Tim D.] Kings Coll London, Dept Twin Res & Genet Epidemiol, London WC2R 2LS, England.
[Sulem, Patrick; Gudbjartsson, Daniel F.; Stacey, Simon N.; Styrkarsdottir, Unnur; Stefansson, Kari; Thorsteinsdottir, Unnur] deCODE Genet, Reykjavik, Iceland.
[Barbalic, Maja; Boerwinkle, Eric] Univ Texas Hlth Sci Ctr Houston, Human Genet Ctr, Houston, TX USA.
[Broer, Linda; van Wingerden, Sophie; Hofman, Albert; Janssens, A. Cecile J. W.; Uitterlinden, Andre G.] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands.
[Visscher, Peter M.] Queensland Inst Med Res, Genet Epidemiol Lab, Brisbane, Qld 4006, Australia.
[Ernst, Florian] Ernst Moritz Arndt Univ Greifswald, Interfakultares Inst Genomforsch, Greifswald, Germany.
[Esko, Tonu; Fischer, Krista; Haller, Toomas; Hass, Merli; Salumets, Andres; Metspalu, Andres] Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia.
[Esko, Tonu; Metspalu, Andres] Estonian Bioctr, Tartu, Estonia.
[Esko, Tonu; Metspalu, Andres] Univ Tartu, Inst Mol & Cell Biol, EE-50090 Tartu, Estonia.
[Franceschini, Nora] Univ N Carolina, Dept Epidemiol, Gillings Sch Global Publ Hlth, Chapel Hill, NC USA.
[Hottenga, Jouke-Jan; de Geus, Eco J. C.; Vink, Jacqueline M.; Willemsen, Gonneke; Boomsma, Dorret I.] Vrije Univ Amsterdam, Dept Biol Psychol, Amsterdam, Netherlands.
[Kraft, Peter; Chen, Constance; Hankinson, Susan E.; Hu, Frank B.; Hunter, David J.] Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA.
[Kraft, Peter; Hofman, Albert; Hunter, David J.] Harvard Univ, Broad Inst, Cambridge, MA 02138 USA.
[Kraft, Peter; Hofman, Albert; Hunter, David J.] MIT, Cambridge, MA 02139 USA.
[McArdle, Patrick F.; Yerges-Armstrong, Laura M.; Streeten, Elizabeth A.] Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA.
[Porcu, Eleonora; Ferreli, Liana; Lai, Sandra; Marongiu, Mara; Crisponi, Laura; Sanna, Serena; Uda, Manuela] CNR, Ist Ric Genet & Biomed, Cagliari, Italy.
[Shin, So-Youn; Deloukas, Panagiotis; Palotie, Aarno; Soranzo, Nicole; Stirrups, Kathleen] Wellcome Trust Sanger Inst, Hinxton, England.
[Smith, Albert V.; Aspelund, Thor; Eiriksdottir, Gudny; Emilsson, Valur; Gudnason, Vilmundur] Iceland Heart Assoc, Kopavogur, Iceland.
[Smith, Albert V.; Aspelund, Thor; Tryggvadottir, Laufey; Gudnason, Vilmundur; Stefansson, Kari; Thorsteinsdottir, Unnur] Univ Iceland, Fac Med, Reykjavik, Iceland.
[Zhai, Guangju] Mem Univ Newfoundland, Fac Med, Discipline Genet, St John, NF, Canada.
[Zhuang, Wei V.; Lunetta, Kathryn L.] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA.
[Albrecht, Eva; Gieger, Christian] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Genet Epidemiol, Neuherberg, Germany.
[Alizadeh, Behrooz Z.; Snieder, Harold; Stolk, Ronald P.] Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, NL-9700 AB Groningen, Netherlands.
[Bandinelli, Stefania] Azienda Sanit Firenze, Geriatr Unit, Florence, Italy.
[Lauc, Lovorka Barac] Croatian Sci Fdn, Zagreb, Croatia.
[Beckmann, Jacques S.; Kutalik, Zoltan] Univ Lausanne, Dept Med Genet, Lausanne, Switzerland.
[Beckmann, Jacques S.] Univ Lausanne Hosp, CHU Vaudois, Serv Med Genet, Lausanne, Switzerland.
[Boban, Mladen; Kolcic, Ivana; Polasek, Ozren; Rudan, Igor; Zemunik, Tatijana] Univ Split, Fac Med, Split, Croatia.
[Broekmans, Frank J.; Fauser, Bart C. J. M.; Voorhuis, Marlies] Univ Med Ctr Utrecht, Dept Reprod Med & Gynaecol, Utrecht, Netherlands.
[Campbell, Harry; Rudan, Igor; Wilson, James F.; Zgaga, Lina] Univ Edinburgh, Ctr Populat Hlth Sci, Edinburgh, Midlothian, Scotland.
[Chanock, Stephen J.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Chen, Constance; Cornelis, Marilyn C.; van Dam, Rob M.; Hu, Frank B.; Hunter, David J.] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA.
[Corre, Tanguy; Masciullo, Corrado; Navarro, Pau; Pistis, Giorgio; Sala, Cinzia; Toniolo, Daniela] Ist Sci San Raffaele, Div Genet & Cell Biol, I-20132 Milan, Italy.
[Coviello, Andrea D.; Glazer, Nicole; Murabito, Joanne M.] Boston Univ, Sch Med, Dept Med, Sect Gen Internal Med Prevent Med & Epidemiol, Boston, MA 02118 USA.
[Coviello, Andrea D.; Johnson, Andrew D.; Karasik, David; Kiel, Douglas P.; Murabito, Joanne M.; Lunetta, Kathryn L.] NHLBI, Framingham Heart Study, Framingham, MA USA.
[d'Adamo, Pio; Gasparini, Paolo; Ulivi, Sheila] Ist Ricovero & Cura Carattere Sci Materno Infanti, Inst Maternal & Child Hlth, Trieste, Italy.
[d'Adamo, Pio; Gasparini, Paolo] Univ Trieste, Trieste, Italy.
[Davies, Gail; Deary, Ian J.; Lopez, Lorna M.] Univ Edinburgh, Dept Psychol, Edinburgh, Midlothian, Scotland.
[de Faire, Ulf] Karolinska Inst, Inst Environm Med, S-10401 Stockholm, Sweden.
[de Geus, Eco J. C.; Boomsma, Dorret I.] Vrije Univ Amsterdam Med Ctr, EMGO Inst Hlth & Care Res, Amsterdam, Netherlands.
[Deary, Ian J.; Lopez, Lorna M.; Starr, John M.; Visscher, Peter M.] Univ Edinburgh, Ctr Cognit Aging & Cognit Epidemiol, Edinburgh, Midlothian, Scotland.
[Dedoussis, George V. Z.; Stathopoulou, Maria G.] Harokopio Univ, Dept Nutr & Dietet, Athens, Greece.
[Ebrahim, Shah] London Sch Hyg & Trop Med, Dept Epidemiol & Populat Hlth, London WC1, England.
[Eriksson, Johan G.] Natl Inst Hlth & Welf, Helsinki, Finland.
[Eriksson, Johan G.] Univ Helsinki, Dept Gen Practice & Primary Hlth Care, Helsinki, Finland.
[Eriksson, Johan G.] Univ Helsinki, Cent Hosp, Unit Gen Practice, Helsinki, Finland.
[Eriksson, Johan G.] Folkhalsan Res Ctr, Helsinki, Finland.
[Eriksson, Johan G.] Vasa Cent Hosp, Vaasa, Finland.
[Ferrucci, Luigi] NIA, Clin Res Branch, Longitudinal Studies Sect, Baltimore, MD 21224 USA.
[Folsom, Aaron R.; Demerath, Ellen W.] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN USA.
[Garcia, Melissa E.; Harris, Tamara B.; Launer, Lenore J.] NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD 20892 USA.
[Grobbee, Diederick E.; Onland-Moret, N. Charlotte; Peeters, Petra H. M.; van der Schouw, Yvonne T.; van Gils, Carla H.; Voorhuis, Marlies] Univ Med Ctr Utrecht, Julius Ctr Hlth Sci & Primary Care, Utrecht, Netherlands.
[Hall, Per; Ingelsson, Erik; Magnusson, Patrik K. E.; Pedersen, Nancy L.; Rehnberg, Emil] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
[Hankinson, Susan E.; Hu, Frank B.; Hunter, David J.] Harvard Univ, Brigham & Womens Hosp, Sch Med, Channing Lab,Dept Med, Boston, MA 02115 USA.
[Hayward, Caroline; Tenesa, Albert; Wright, Alan F.] Univ Edinburgh, Western Gen Hosp, MRC Inst Genet & Mol Med, Med Res Council MRC,Human Genet Unit, Edinburgh, Midlothian, Scotland.
[Heath, Andrew C.] Washington Univ, St Louis, MO USA.
[Karasik, David; Kiel, Douglas P.] Harvard Univ, Sch Med, Hebrew Senior Life Inst Aging Res, Boston, MA USA.
[Kardia, Sharon L. R.; Smith, Jennifer A.] Univ Michigan, Dept Epidemiol, Ann Arbor, MI 48109 USA.
[Keyzer, Jules] Diagnost GP Lab Eindhoven, Eindhoven, Netherlands.
[Kutalik, Zoltan] Swiss Inst Bioinformat, Lausanne, Switzerland.
[Lahti, Jari; Raikkonen, Katri] Univ Helsinki, Inst Behav Sci, Helsinki, Finland.
[Laisk, Triin; Salumets, Andres] Univ Tartu, Dept Obstet & Gynecol, EE-50090 Tartu, Estonia.
[Laven, Joop S. E.; Louwers, Yvonne V.] Erasmus MC, Dept Obstet & Gynaecol, Div Reprod Med, Rotterdam, Netherlands.
[Lawlor, Debbie A.] Univ Bristol, Sch Social & Community Med, MRC Ctr Causal Anal Translat Epidemiol, Bristol, Avon, England.
[Liu, Jianjun] Genome Inst Singapore, Singapore, Singapore.
[Klaric, Irena Martinovic] Inst Migrat & Ethn Studies, Zagreb, Croatia.
[McKnight, Barbara; Arnold, Alice M.] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Mooser, Vincent] GlaxoSmithKline, Div Genet, King Of Prussia, PA USA.
[Newman, Anne B.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA.
[Newman, Anne B.] Univ Pittsburgh, Dept Med, Pittsburgh, PA USA.
[Palotie, Aarno; Widen, Elisabeth] Univ Helsinki, Inst Mol Med Finland, Helsinki, Finland.
[Palotie, Aarno] Univ Helsinki, Dept Med Genet, Cent Hosp, Helsinki, Finland.
[Pare, Guillaume] McMaster Univ, Genet & Mol Epidemiol Lab, Hamilton, ON, Canada.
[Parker, Alex N.; Tsui, Kim] Amgen Inc, Cambridge, MA USA.
[Parker, Alex N.] Fdn Med, Cambridge, MA USA.
[Peeters, Petra H. M.] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, Fac Med, Dept Epidemiol & Biostat, London, England.
[Plump, Andrew S.] Merck Res Lab, Rahway, NJ USA.
[Pop, Victor J. M.] Tilburg Univ, Dept Clin Hlth Psychol, NL-5000 LE Tilburg, Netherlands.
[Psaty, Bruce M.] Univ Washington, Dept Med, 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 Res Inst, Grp Hlth Cooperat, Seattle, WA USA.
[Rotter, Jerome I.] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA.
[Salumets, Andres; Metspalu, Andres] Competence Ctr Reprod Med & Biol, Tartu, Estonia.
[Scuteri, Angelo] NIA, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA.
[Singleton, Andrew] NIA, Neurogenet Lab, Bethesda, MD 20892 USA.
[Snieder, Harold; Stolk, Ronald P.; Wolffenbuttel, Bruce H. R.] Univ Groningen, Univ Med Ctr Groningen, LifeLines Cohort Study, Groningen, Netherlands.
[Snieder, Harold; Stolk, Ronald P.; Wolffenbuttel, Bruce H. R.; LifeLines Cohort Study] Univ Groningen, Univ Med Ctr Groningen, Biobank, Groningen, Netherlands.
[Starr, John M.] Univ Edinburgh, Geriatr Med Unit, Edinburgh, Midlothian, Scotland.
[Stathopoulou, Maria G.] Univ Henri Poincare, Cardiovasc Genet Res Unit, Nancy, France.
[Sun, Yan V.] Emory Univ, Dept Epidemiol, Atlanta, GA 30322 USA.
[Tenesa, Albert] Univ Edinburgh, Royal Dick Sch Vet Studies, Roslin Inst, Roslin, Midlothian, Scotland.
[Thorand, Barbara] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 2, Neuherberg, Germany.
[Toniolo, Daniela] CNR, Inst Mol Genet, Pavia, Italy.
[Tryggvadottir, Laufey] Iceland Canc Registry, Reykjavik, Iceland.
[van Dam, Rob M.] Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore 117548, Singapore.
[van Dam, Rob M.] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Med, Singapore 117595, Singapore.
[van Nierop, Peter] Municipal Hlth Serv Brabant Zuidoost, Helmond, Netherlands.
[Waeber, Gerard] Univ Lausanne Hosp, CHUV, Dept Internal Med, Lausanne, Switzerland.
[Wallaschofski, Henri] Ernst Moritz Arndt Univ Greifswald, Inst Clin Chem & Lab Med, Greifswald, Germany.
[Wichmann, H. Erich] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Epidemiol 1, Neuherberg, Germany.
[Wichmann, H. Erich] Univ Munich, Inst Med Informat Biometry & Epidemiol, Munich, Germany.
[Wichmann, H. Erich] Univ Munich, Klinikum Grosshadern, D-8000 Munich, Germany.
[Wijnands-van Gent, Colette J. M.] POZOB Veldhoven, Veldhoven, Netherlands.
[Wolffenbuttel, Bruce H. R.] Univ Groningen, Univ Med Ctr Groningen, Dept Epidemiol, NL-9700 AB Groningen, Netherlands.
[Zgaga, Lina] Univ Zagreb, Sch Med, Andrija Stampar Sch Publ Hlth, Zagreb 41001, Croatia.
[Zygmunt, Marek] Ernst Moritz Arndt Univ Greifswald, Klin Gynakol & Geburtshilfe, Greifswald, Germany.
[Oostra, Ben A.] Erasmus MC, Dept Clin Genet, Rotterdam, Netherlands.
[Ridker, Paul M.] Brigham & Womens Hosp, Div Cardiol, Boston, MA 02115 USA.
[Schlessinger, David] NIA, Intramural Res Program, Baltimore, MD 21224 USA.
[Voelzke, Henry] Ernst Moritz Arndt Univ Greifswald, Inst Community Med, Greifswald, Germany.
RP Murray, A (reprint author), Univ Exeter, Peninsula Med Sch, Exeter, Devon, England.
EM anna.murray@pms.ac.uk; klunetta@bu.edu
RI Polasek, Ozren/B-6002-2011; de Geus, Eco/M-9318-2015; Montgomery,
Grant/B-7148-2008; Smith, Albert/K-5150-2015; Stathopoulou,
Maria/H-7324-2016; mangino, massimo/F-5134-2011; Hayward,
Caroline/M-8818-2016; Magnusson, Patrik/C-4458-2017; Boban,
Mladen/E-2777-2017; Kolcic, Ivana/E-2713-2017; Byrne, Enda/J-6068-2014;
Johnson, Andrew/G-6520-2013; Ulivi, Sheila/H-3700-2013; Aspelund,
Thor/C-5983-2008; Grobbee, Diederick/C-7651-2014; Newman,
Anne/C-6408-2013; Thorand, Barbara/B-5349-2014; Colaus,
PsyColaus/K-6607-2013; Laisk, Triin/J-2290-2015; Salumets,
Andres/J-2278-2015; Onland-Moret, N. Charlotte/G-9185-2011; Gudnason,
Vilmundur/K-6885-2015; Wilson, James F/A-5704-2009; Beckmann, Jacques S
/A-9772-2008; Singleton, Andrew/C-3010-2009; Stolk, Ronald/B-2341-2013;
Deloukas, Panos/B-2922-2013; Wolffenbuttel, Bruce/A-8419-2011; d'Adamo,
Adamo Pio/G-4064-2011; Medland, Sarah/C-7630-2013; Deary,
Ian/C-6297-2009; van Dam, Rob/F-9674-2010; Visser, Jenny /F-8156-2011;
Rudan, Igor/I-1467-2012; Lopez, Lorna/F-7265-2010; Nyholt,
Dale/C-8384-2013
OI Martin, Nicholas/0000-0003-4069-8020; Ziad Alizadeh,
Behrooz/0000-0002-1415-8007; Visscher, Peter/0000-0002-2143-8760;
Eriksson, Johan/0000-0002-2516-2060; Smith,
Jennifer/0000-0002-3575-5468; Lahti, Jari/0000-0002-4310-5297; Lawlor,
Debbie A/0000-0002-6793-2262; Raikkonen, Katri/0000-0003-3124-3470;
Esko, Tonu/0000-0003-1982-6569; Tryggvadottir,
Laufey/0000-0001-8067-9030; Soranzo, Nicole/0000-0003-1095-3852; Gieger,
Christian/0000-0001-6986-9554; Kiel, Douglas/0000-0001-8474-0310;
Melzer, David/0000-0002-0170-3838; Karasik, David/0000-0002-8826-0530;
MARONGIU, MARA/0000-0002-7321-2384; Zgaga, Lina/0000-0003-4089-9703;
Murray, Anna/0000-0002-2351-2522; sanna, serena/0000-0002-3768-1749;
Gudbjartsson, Daniel/0000-0002-5222-9857; Janssens, A
Cecile/0000-0002-6153-4976; Polasek, Ozren/0000-0002-5765-1862; de Geus,
Eco/0000-0001-6022-2666; Montgomery, Grant/0000-0002-4140-8139; Smith,
Albert/0000-0003-1942-5845; Stathopoulou, Maria/0000-0003-4376-2083;
mangino, massimo/0000-0002-2167-7470; Hayward,
Caroline/0000-0002-9405-9550; Kolcic, Ivana/0000-0001-7918-6052; Byrne,
Enda/0000-0002-9491-7797; Murabito, Joanne/0000-0002-0192-7516; Lunetta,
Kathryn/0000-0002-9268-810X; Ulivi, Sheila/0000-0003-3606-835X;
Aspelund, Thor/0000-0002-7998-5433; Grobbee,
Diederick/0000-0003-4472-4468; Newman, Anne/0000-0002-0106-1150;
Thorand, Barbara/0000-0002-8416-6440; Salumets,
Andres/0000-0002-1251-8160; Gudnason, Vilmundur/0000-0001-5696-0084;
Wilson, James F/0000-0001-5751-9178; Beckmann, Jacques S
/0000-0002-9741-1900; Stolk, Ronald/0000-0002-0518-1205; Deloukas,
Panos/0000-0001-9251-070X; Wolffenbuttel, Bruce/0000-0001-9262-6921;
d'Adamo, Adamo Pio/0000-0001-9367-4909; Medland,
Sarah/0000-0003-1382-380X; van Dam, Rob/0000-0002-7354-8734; Rudan,
Igor/0000-0001-6993-6884;
FU Biotechnology and Biological Sciences Research Council [BB/F019394/1];
Chief Scientist Office [CZB/4/710]; Medical Research Council [G0600705,
G0700704, MC_PC_U127561128, MC_PC_U127592696, MC_U127561128,
MC_U127592696]; NCATS NIH HHS [UL1 TR000124]; NCI NIH HHS [P01 CA087969,
P01 CA087969-12, R01 CA040356-15, R01 CA047988, R01 CA047988-09, U01
CA098233, U01 CA098233-01]; NHGRI NIH HHS [U01 HG004402, U01
HG004402-01]; NHLBI NIH HHS [N01 HC025195, N01 HC035129, N01 HC055015,
N01 HC085086, N02 HL64278, R01 HL043851, R01 HL043851-09, R01 HL087660,
R01 HL087660-01, R01 HL105756, R01 HL105756-01, U01 HL072515, U01
HL072515-01, U01 HL084756, U01 HL084756-01]; NIA NIH HHS [N01 AG012100,
N01 AG012109, N01 AG050002, R21 AG032598, R21 AG032598-01]; NIAAA NIH
HHS [K05 AA017688]; NIAMS NIH HHS [R01 AR041398, R01 AR041398-09]; NIDDK
NIH HHS [P30 DK063491, P30 DK072488]; NIMHD NIH HHS [263 MD821336, 263
MD9164 13]; The Dunhill Medical Trust [R69/0208]
NR 81
TC 120
Z9 123
U1 8
U2 62
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 MAR
PY 2012
VL 44
IS 3
BP 260
EP U55
DI 10.1038/ng.1051
PG 11
WC Genetics & Heredity
SC Genetics & Heredity
GA 899VC
UT WOS:000300843600010
PM 22267201
ER
PT J
AU Ghoussaini, M
Fletcher, O
Michailidou, K
Turnbull, C
Schmidt, MK
Dicks, E
Dennis, J
Wang, Q
Humphreys, MK
Luccarini, C
Baynes, C
Conroy, D
Maranian, M
Ahmed, S
Driver, K
Johnson, N
Orr, N
Silva, ID
Waisfisz, Q
Meijers-Heijboer, H
Uitterlinden, AG
Rivadeneira, F
Hall, P
Czene, K
Irwanto, A
Liu, JJ
Nevanlinna, H
Aittomaki, K
Blomqvist, C
Meindl, A
Schmutzler, RK
Muller-Myhsok, B
Lichtner, P
Chang-Claude, J
Hein, R
Nickels, S
Flesch-Janys, D
Tsimiklis, H
Makalic, E
Schmidt, D
Bui, M
Hopper, JL
Apicella, C
Park, DJ
Southey, M
Hunter, DJ
Chanock, SJ
Broeks, A
Verhoef, S
Hogervorst, FBL
Fasching, PA
Lux, MP
Beckmann, MW
Ekici, AB
Sawyer, E
Tomlinson, I
Kerin, M
Marme, F
Schneeweiss, A
Sohn, C
Burwinkel, B
Guenel, P
Truong, T
Cordina-Duverger, E
Menegaux, F
Bojesen, SE
Nordestgaard, BG
Nielsen, SF
Flyger, H
Milne, RL
Alonso, MR
Gonzalez-Neira, A
Benitez, J
Anton-Culver, H
Ziogas, A
Bernstein, L
Dur, CC
Brenner, H
Muller, H
Arndt, V
Stegmaier, C
Justenhoven, C
Brauch, H
Bruning, T
Wang-Gohrke, S
Eilber, U
Dork, T
Schurmann, P
Bremer, M
Hillemanns, P
Bogdanova, NV
Antonenkova, NN
Rogov, YI
Karstens, JH
Bermisheva, M
Prokofieva, D
Khusnutdinova, E
Lindblom, A
Margolin, S
Mannermaa, A
Kataja, V
Kosma, VM
Hartikainen, JM
Lambrechts, D
Yesilyurt, BT
Floris, G
Leunen, K
Manoukian, S
Bonanni, B
Fortuzzi, S
Peterlongo, P
Couch, FJ
Wang, XS
Stevens, K
Lee, A
Giles, GG
Baglietto, L
Severi, G
McLean, C
Alnaes, GG
Kristensen, V
Borrensen-Dale, AL
John, EM
Miron, A
Winqvist, R
Pylkas, K
Jukkola-Vuorinen, A
Kauppila, S
Andrulis, IL
Glendon, G
Mulligan, AM
Devilee, P
van Asperen, CJ
Tollenaar, RAEM
Seynaeve, C
Figueroa, JD
Garcia-Closas, M
Brinton, L
Lissowska, J
Hooning, MJ
Hollestelle, A
Oldenburg, RA
van den Ouweland, AMW
Cox, A
Reed, MWR
Shah, M
Jakubowska, A
Lubinski, J
Jaworska, K
Durda, K
Jones, M
Schoemaker, M
Ashworth, A
Swerdlow, A
Beesley, J
Chen, XQ
Muir, KR
Lophatananon, A
Rattanamongkongul, S
Chaiwerawattana, A
Kang, D
Yoo, KY
Noh, DY
Shen, CY
Yu, JC
Wu, PE
Hsiung, CN
Perkins, A
Swann, R
Velentzis, L
Eccles, DM
Tapper, WJ
Gerty, SM
Graham, NJ
Ponder, BAJ
Chenevix-Trench, G
Pharoah, PDP
Lathrop, M
Dunning, AM
Rahman, N
Peto, J
Easton, DF
AF Ghoussaini, Maya
Fletcher, Olivia
Michailidou, Kyriaki
Turnbull, Clare
Schmidt, Marjanka K.
Dicks, Ed
Dennis, Joe
Wang, Qin
Humphreys, Manjeet K.
Luccarini, Craig
Baynes, Caroline
Conroy, Don
Maranian, Melanie
Ahmed, Shahana
Driver, Kristy
Johnson, Nichola
Orr, Nicholas
Silva, Isabel dos Santos
Waisfisz, Quinten
Meijers-Heijboer, Hanne
Uitterlinden, Andre G.
Rivadeneira, Fernando
Hall, Per
Czene, Kamila
Irwanto, Astrid
Liu, Jianjun
Nevanlinna, Heli
Aittomaki, Kristiina
Blomqvist, Carl
Meindl, Alfons
Schmutzler, Rita K.
Mueller-Myhsok, Bertram
Lichtner, Peter
Chang-Claude, Jenny
Hein, Rebecca
Nickels, Stefan
Flesch-Janys, Dieter
Tsimiklis, Helen
Makalic, Enes
Schmidt, Daniel
Bui, Minh
Hopper, John L.
Apicella, Carmel
Park, Daniel J.
Southey, Melissa
Hunter, David J.
Chanock, Stephen J.
Broeks, Annegien
Verhoef, Senno
Hogervorst, Frans B. L.
Fasching, Peter A.
Lux, Michael P.
Beckmann, Matthias W.
Ekici, Arif B.
Sawyer, Elinor
Tomlinson, Ian
Kerin, Michael
Marme, Frederik
Schneeweiss, Andreas
Sohn, Christof
Burwinkel, Barbara
Guenel, Pascal
Truong, Therese
Cordina-Duverger, Emilie
Menegaux, Florence
Bojesen, Stig E.
Nordestgaard, Borge G.
Nielsen, Sune F.
Flyger, Henrik
Milne, Roger L.
Rosario Alonso, M.
Gonzalez-Neira, Anna
Benitez, Javier
Anton-Culver, Hoda
Ziogas, Argyrios
Bernstein, Leslie
Dur, Christina Clarke
Brenner, Hermann
Mueller, Heiko
Arndt, Volker
Stegmaier, Christa
Justenhoven, Christina
Brauch, Hiltrud
Bruening, Thomas
Wang-Gohrke, Shan
Eilber, Ursula
Doerk, Thilo
Schuermann, Peter
Bremer, Michael
Hillemanns, Peter
Bogdanova, Natalia V.
Antonenkova, Natalia N.
Rogov, Yuri I.
Karstens, Johann H.
Bermisheva, Marina
Prokofieva, Darya
Khusnutdinova, Elza
Lindblom, Annika
Margolin, Sara
Mannermaa, Arto
Kataja, Vesa
Kosma, Veli-Matti
Hartikainen, Jaana M.
Lambrechts, Diether
Yesilyurt, Betul T.
Floris, Giuseppe
Leunen, Karin
Manoukian, Siranoush
Bonanni, Bernardo
Fortuzzi, Stefano
Peterlongo, Paolo
Couch, Fergus J.
Wang, Xianshu
Stevens, Kristen
Lee, Adam
Giles, Graham G.
Baglietto, Laura
Severi, Gianluca
McLean, Catriona
Alnaes, Grethe Grenaker
Kristensen, Vessela
Borrensen-Dale, Anne-Lise
John, Esther M.
Miron, Alexander
Winqvist, Robert
Pylkas, Katri
Jukkola-Vuorinen, Arja
Kauppila, Saila
Andrulis, Irene L.
Glendon, Gord
Mulligan, Anna Marie
Devilee, Peter
van Asperen, Christie J.
Tollenaar, Rob A. E. M.
Seynaeve, Caroline
Figueroa, Jonine D.
Garcia-Closas, Montserrat
Brinton, Louise
Lissowska, Jolanta
Hooning, Maartje J.
Hollestelle, Antoinette
Oldenburg, Rogier A.
van den Ouweland, Ans M. W.
Cox, Angela
Reed, Malcolm W. R.
Shah, Mitul
Jakubowska, Ania
Lubinski, Jan
Jaworska, Katarzyna
Durda, Katarzyna
Jones, Michael
Schoemaker, Minouk
Ashworth, Alan
Swerdlow, Anthony
Beesley, Jonathan
Chen, Xiaoqing
Muir, Kenneth R.
Lophatananon, Artitaya
Rattanamongkongul, Suthee
Chaiwerawattana, Arkom
Kang, Daehee
Yoo, Keun-Young
Noh, Dong-Young
Shen, Chen-Yang
Yu, Jyh-Cherng
Wu, Pei-Ei
Hsiung, Chia-Ni
Perkins, Annie
Swann, Ruth
Velentzis, Louiza
Eccles, Diana M.
Tapper, Will J.
Gerty, Susan M.
Graham, Nikki J.
Ponder, Bruce A. J.
Chenevix-Trench, Georgia
Pharoah, Paul D. P.
Lathrop, Mark
Dunning, Alison M.
Rahman, Nazneen
Peto, Julian
Easton, Douglas F.
CA Netherlands Collaborative Grp Here
FBCS
Gene Environm Interaction Breast C
kConFab Investigators
Australian Ovarian Canc Study Grp
TI Genome-wide association analysis identifies three new breast cancer
susceptibility loci
SO NATURE GENETICS
LA English
DT Article
ID HORMONE-RELATED PROTEIN; DEVELOPMENTAL REGULATORY MOLECULE;
ULNAR-MAMMARY SYNDROME; PARATHYROID-HORMONE; NEGATIVE-FEEDBACK; COMMON
VARIANTS; CONFER SUSCEPTIBILITY; GENE-EXPRESSION; CELL CARCINOMA;
RETINOIC ACID
AB Breast cancer is the most common cancer among women. To date, 22 common breast cancer susceptibility loci have been identified accounting for similar to 8% of the heritability of the disease. We attempted to replicate 72 promising associations from two independent genome-wide association studies (GWAS) in similar to 70,000 cases and similar to 68,000 controls from 41 case-control studies and 9 breast cancer GWAS. We identified three new breast cancer risk loci at 12p11 (rs10771399; P = 2.7 x 10(-35)), 12q24 (rs1292011; P = 4.3 x 10(-19)) and 21q21 (rs2823093; P = 1.1 x 10(-12)). rs10771399 was associated with similar relative risks for both estrogen receptor (ER)-negative and ER-positive breast cancer, whereas the other two loci were associated only with ER-positive disease. Two of the loci lie in regions that contain strong plausible candidate genes: PTHLH (12p11) has a crucial role in mammary gland development and the establishment of bone metastasis in breast cancer, and NRIP1 (21q21) encodes an ER cofactor and has a role in the regulation of breast cancer cell growth.
C1 [Ghoussaini, Maya; Dicks, Ed; Luccarini, Craig; Baynes, Caroline; Conroy, Don; Maranian, Melanie; Ahmed, Shahana; Driver, Kristy; Shah, Mitul; Pharoah, Paul D. P.; Dunning, Alison M.; Easton, Douglas F.] Univ Cambridge, Dept Oncol, Ctr Canc Genet Epidemiol, Cambridge, England.
[Fletcher, Olivia; Johnson, Nichola; Orr, Nicholas; Ashworth, Alan] Inst Canc Res, Breakthrough Breast Canc Res Ctr, London SW3 6JB, England.
[Michailidou, Kyriaki; Dennis, Joe; Wang, Qin; Humphreys, Manjeet K.; Pharoah, Paul D. P.; Easton, Douglas F.] Univ Cambridge, Ctr Canc Genet Epidemiol, Dept Publ Hlth & Primary Care, Cambridge, England.
[Turnbull, Clare; Garcia-Closas, Montserrat; Rahman, Nazneen; FBCS] Inst Canc Res, Sect Canc Genet, Sutton, Surrey, England.
[Schmidt, Marjanka K.; Broeks, Annegien] Antoni Van Leeuwenhoek Hosp, Netherlands Canc Inst, Dept Expt Therapy, Amsterdam, Netherlands.
[Schmidt, Marjanka K.] Antoni Van Leeuwenhoek Hosp, Netherlands Canc Inst, Dept Epidemiol, Amsterdam, Netherlands.
[Silva, Isabel dos Santos; Peto, Julian] London Sch Hyg & Trop Med, Noncommunicable Dis Epidemiol Dept, London WC1, England.
[Waisfisz, Quinten; Meijers-Heijboer, Hanne] Vrije Univ Amsterdam Med Ctr, Sect Oncogenet, Dept Clin Genet, Amsterdam, Netherlands.
[Uitterlinden, Andre G.; Rivadeneira, Fernando] Erasmus MC, Dept Internal Med & Epidemiol, Rotterdam, Netherlands.
[Hall, Per; Czene, Kamila] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden.
[Irwanto, Astrid; Nevanlinna, Heli] Univ Helsinki, Dept Obstet & Gynecol, Helsinki, Finland.
[Irwanto, Astrid; Nevanlinna, Heli; Aittomaki, Kristiina; Blomqvist, Carl] Univ Helsinki, Cent Hosp, Helsinki, Finland.
[Liu, Jianjun] Genome Inst Singapore, Human Genet Div, Singapore, Singapore.
[Aittomaki, Kristiina] Univ Helsinki, Dept Clin Genet, Helsinki, Finland.
[Blomqvist, Carl] Univ Helsinki, Dept Oncol, Helsinki, Finland.
[Meindl, Alfons] Tech Univ Munich, Div Gynaecol Tumor Genet, Clin Gynaecol & Obstet, Munich, Germany.
[Schmutzler, Rita K.] Univ Cologne, Dept Obstet & Gynaecol, Div Mol Gynaecooncol, D-50931 Cologne, Germany.
[Mueller-Myhsok, Bertram] Max Planck Inst Psychiat, D-80804 Munich, Germany.
[Lichtner, Peter] German Res Ctr Environm Hlth, Helmholtz Zentrum Munchen, Inst Human Genet, Neuherberg, Germany.
[Chang-Claude, Jenny; Hein, Rebecca; Nickels, Stefan; Eilber, Ursula] Deutsch Krebsforschungszentrum, Div Canc Epidemiol, D-6900 Heidelberg, Germany.
[Hein, Rebecca] Univ Cologne, Dept Child & Adolescent Psychiat & Psychotherapy, Primar Med Versorgung PMV Res Grp, D-50931 Cologne, Germany.
[Flesch-Janys, Dieter] Univ Clin Hamburg Eppendorf, Clin Canc Registry, Dept Canc Epidemiol, Hamburg, Germany.
[Flesch-Janys, Dieter] Univ Clin Hamburg Eppendorf, Inst Med Biometr & Epidemiol, Hamburg, Germany.
[Tsimiklis, Helen; Park, Daniel J.; Southey, Melissa] Univ Melbourne, Dept Pathol, Genet Epidemiol Lab, Melbourne, Vic, Australia.
[Makalic, Enes; Schmidt, Daniel; Bui, Minh; Hopper, John L.; Apicella, Carmel; Giles, Graham G.; Baglietto, Laura; Severi, Gianluca] Univ Melbourne, Melbourne Sch Populat Hlth, Ctr Mol Environm Genet & Analyt Epidemiol, Melbourne, Vic, Australia.
[Hunter, David J.] Harvard Univ, Sch Publ Hlth, Program Mol & Genet Epidemiol, Boston, MA 02115 USA.
[Chanock, Stephen J.; Figueroa, Jonine D.; Brinton, Louise] NCI, Div Canc Epidemiol & Genet, Rockville, MD USA.
[Verhoef, Senno] Antoni Van Leeuwenhoek Hosp, Netherlands Canc Inst, Family Canc Clin, Dept Clin Genet, Amsterdam, Netherlands.
[Hogervorst, Frans B. L.] Antoni Van Leeuwenhoek Hosp, Netherlands Canc Inst, Family Canc Clin, Dept Mol Pathol, Amsterdam, Netherlands.
[Fasching, Peter A.; Lux, Michael P.; Beckmann, Matthias W.] Univ Hosp Erlangen, Univ Breast Ctr, Dept Gynecol & Obstet, Erlangen, Germany.
[Ekici, Arif B.] Univ Erlangen Nurnberg, Inst Human Genet, Erlangen, Germany.
[Sawyer, Elinor] Guys & St Thomas Natl Hlth Serv NHS Fdn Trust, Div Canc Studies, Natl Inst Hlth Res NIHR Comprehens Biomed Res Ctr, London, England.
[Sawyer, Elinor] Kings Coll London, Div Canc Studies, London WC2R 2LS, England.
[Tomlinson, Ian] Univ Oxford, Oxford Biomed Res Ctr, Oxford, England.
[Tomlinson, Ian] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.
[Kerin, Michael] Univ Hosp Galway, Inst Clin Sci, Galway, Ireland.
[Marme, Frederik; Schneeweiss, Andreas; Sohn, Christof; Burwinkel, Barbara] Heidelberg Univ, Dept Obstet & Gynecol, Heidelberg, Germany.
[Marme, Frederik; Schneeweiss, Andreas] Heidelberg Univ, Natl Ctr Tumor Dis, Heidelberg, Germany.
[Burwinkel, Barbara] German Canc Res Ctr, Mol Epidemiol Unit, Heidelberg, Germany.
[Guenel, Pascal; Truong, Therese; Cordina-Duverger, Emilie; Menegaux, Florence] Ctr Rech Epidemiol & Populat Hlth CESP, INSERM, U1018, Villejuif, France.
[Guenel, Pascal; Truong, Therese; Cordina-Duverger, Emilie; Menegaux, Florence] Univ Paris 11, Unite Mixte Rech Sante UMRS 1018, Villejuif, France.
[Bojesen, Stig E.; Nordestgaard, Borge G.; Nielsen, Sune F.] Copenhagen Univ Hosp, Herlev Hosp, Copenhagen Gen Populat Study, Copenhagen, Denmark.
[Bojesen, Stig E.; Nordestgaard, Borge G.; Nielsen, Sune F.] Copenhagen Univ Hosp, Herlev Hosp, Dept Clin Biochem, Copenhagen, Denmark.
[Flyger, Henrik] Copenhagen Univ Hosp, Herlev Hosp, Dept Breast Surg, Copenhagen, Denmark.
[Milne, Roger L.] Spanish Natl Canc Res Ctr CNIO, Human Canc Genet Programme, Genet & Mol Epidemiol Grp, Madrid, Spain.
[Rosario Alonso, M.; Gonzalez-Neira, Anna] CNIO, Human Canc Genet Programme, Human Genotyping Unit, Madrid, Spain.
[Benitez, Javier] CNIO, Human Canc Genet Programme, Human Genet Grp, Madrid, Spain.
[Anton-Culver, Hoda; Ziogas, Argyrios] Univ Calif Irvine, Dept Epidemiol, Irvine, CA USA.
[Bernstein, Leslie] City Hope Canc Ctr, Duarte, CA USA.
[Dur, Christina Clarke; John, Esther M.] Canc Prevent Inst Calif, Fremont, CA USA.
[Brenner, Hermann; Mueller, Heiko; Arndt, Volker] German Canc Res Ctr, Div Clin Epidemiol & Aging Res, Heidelberg, Germany.
[Stegmaier, Christa] Saarland Canc Registry, Saarbrucken, Germany.
[Justenhoven, Christina; Brauch, Hiltrud] Dr Margarete Fischer Bosch Inst Clin Pharmacol, D-7000 Stuttgart, Germany.
[Justenhoven, Christina; Brauch, Hiltrud] Univ Tubingen, Tubingen, Germany.
[Bruening, Thomas] German Social Accid Insurance IPA, Inst Prevent & Occupat Med, Bochum, Germany.
DKFZ, Heidelberg, Germany.
[Gene Environm Interaction Breast C] Johanniter Krankenhaus, Evangel Kliniken Bonn, Dept Internal Med, Bonn, Germany.
[Wang-Gohrke, Shan] Univ Ulm, Dept Obstet & Gynecol, Ulm, Germany.
[Doerk, Thilo; Schuermann, Peter; Bremer, Michael; Hillemanns, Peter] Hannover Med Sch, Dept Obstet & Gynaecol, D-3000 Hannover, Germany.
[Bogdanova, Natalia V.; Karstens, Johann H.] Hannover Med Sch, Dept Radiat Oncol, D-3000 Hannover, Germany.
[Antonenkova, Natalia N.; Rogov, Yuri I.] NN Alexandrov Res Inst Oncol & Med Radiol, Minsk, Byelarus.
[Bermisheva, Marina; Prokofieva, Darya; Khusnutdinova, Elza] Russian Acad Sci, Ufa Sci Ctr, Inst Biochem & Genet, Ufa 450001, Russia.
[Lindblom, Annika] Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden.
[Margolin, Sara] Karolinska Inst, Dept Oncol Pathol, Stockholm, Sweden.
[Mannermaa, Arto; Kosma, Veli-Matti; Hartikainen, Jaana M.] Univ Eastern Finland, Inst Clin Med, Sch Med, Dept Pathol & Forens Med, Kuopio, Finland.
[Mannermaa, Arto; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M.; Lee, Adam] Univ Eastern Finland, Bioctr Kuopio, Kuopio, Finland.
[Mannermaa, Arto; Kosma, Veli-Matti; Hartikainen, Jaana M.] Kuopio Univ Hosp, Dept Clin Pathol, SF-70210 Kuopio, Finland.
[Kataja, Vesa] Univ Eastern Finland, Inst Clin Med, Sch Med, Dept Oncol, Kuopio, Finland.
[Kataja, Vesa] Kuopio Univ Hosp, Dept Oncol, SF-70210 Kuopio, Finland.
[Lambrechts, Diether; Yesilyurt, Betul T.] VIB, VRC, Louvain, Belgium.
[Floris, Giuseppe; Leunen, Karin] Univ Hosp Gasthuisberg, Multidisciplinary Breast Ctr, B-3000 Louvain, Belgium.
[Manoukian, Siranoush] Ist Nazl Tumori, Unit Med Genet, Dept Prevent & Predict Med, Fdn Ist Ricovero & Cura Carattere Sci IRCCS, I-20133 Milan, Italy.
[Bonanni, Bernardo] IEO, Div Canc Prevent & Genet, Milan, Italy.
[Fortuzzi, Stefano; Peterlongo, Paolo] Ist FIRC Fdn Italiana Ric Canc Oncol Mol IFOM, Milan, Italy.
[Peterlongo, Paolo] Fdn IRCCS INT, Unit Mol Bases Genet Risk & Genet Testing, Dept Prevent & Predict Med, Milan, Italy.
[Couch, Fergus J.; Wang, Xianshu] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA.
[Couch, Fergus J.; Stevens, Kristen] Mayo Clin, Dept Hlth Sci Res, Rochester, MN USA.
[Lee, Adam] Mayo Clin, Dept Pharmacol, Rochester, MN USA.
[Giles, Graham G.; Baglietto, Laura; Severi, Gianluca] Canc Council Victoria, Canc Epidemiol Ctr, Melbourne, Vic, Australia.
[McLean, Catriona] Alfred Hosp, Dept Anat Pathol, Melbourne, Vic, Australia.
[Alnaes, Grethe Grenaker; Kristensen, Vessela; Borrensen-Dale, Anne-Lise] Radiumhosp, Dept Genet, Inst Canc Res, Oslo Univ Hosp, Oslo, Norway.
[Kristensen, Vessela; Borrensen-Dale, Anne-Lise] Univ Oslo, Inst Clin Med, Fac Med, Oslo, Norway.
[John, Esther M.] Stanford Univ, Dept Hlth Res Policy, Div Epidemiol, Sch Med, Stanford, CA 94305 USA.
[Miron, Alexander] Dana Farber Canc Ctr, Boston, MA USA.
[Winqvist, Robert; Pylkas, Katri] Univ Oulu, Oulu Univ Hosp, Dept Clin Genet, Lab Canc Genet, Oulu, Finland.
[Winqvist, Robert; Pylkas, Katri] Univ Oulu, Oulu Univ Hosp, Bioctr Oulu, Oulu, Finland.
[Jukkola-Vuorinen, Arja] Univ Oulu, Oulu Univ Hosp, Dept Oncol, Oulu, Finland.
[Kauppila, Saila] Univ Oulu, Dept Pathol, Oulu Univ Hosp, Oulu, Finland.
[Andrulis, Irene L.] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Fred A Litwin Ctr Canc Genet, Toronto, ON M5G 1X5, Canada.
[Andrulis, Irene L.] Univ Toronto, Dept Mol Genet, Toronto, ON, Canada.
[Glendon, Gord] Canc Care Ontario, Ontario Canc Genet Network, Toronto, ON, Canada.
[Mulligan, Anna Marie] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON, Canada.
[Mulligan, Anna Marie] St Michaels Hosp, Li Ka Shing Knowledge Inst, Dept Lab Med, Toronto, ON M5B 1W8, Canada.
[Mulligan, Anna Marie] St Michaels Hosp, Li Ka Shing Knowledge Inst, Keenan Res Ctr, Toronto, ON M5B 1W8, Canada.
[Devilee, Peter] Leiden Univ, Med Ctr, Dept Human Genet, Leiden, Netherlands.
[Devilee, Peter] Leiden Univ, Dept Pathol, Med Ctr, Leiden, Netherlands.
[van Asperen, Christie J.] Leiden Univ, Dept Clin Genet, Med Ctr, Leiden, Netherlands.
[Tollenaar, Rob A. E. M.] Leiden Univ, Dept Surg, Med Ctr, Leiden, Netherlands.
[Seynaeve, Caroline] Erasmus MC Daniel den Hoed Canc Ctr, Rotterdam Family Canc Clin, Dept Med Oncol, Rotterdam, Netherlands.
[Garcia-Closas, Montserrat; Jones, Michael; Schoemaker, Minouk; Swerdlow, Anthony] Inst Canc Res, Epidemiol Sect, Sutton, Surrey, England.
[Lissowska, Jolanta] M Sklodowska Curie Mem Canc Ctr, Dept Canc Epidemiol & Prevent, Warsaw, Poland.
[Lissowska, Jolanta] Inst Oncol, Warsaw, Poland.
[Hooning, Maartje J.] Erasmus Univ, Dept Med Oncol, Family Canc Clin, Med Ctr, Rotterdam, Netherlands.
[Hollestelle, Antoinette] Erasmus Univ, Dept Med Oncol, Josephine Nefkens Inst, Med Ctr, Rotterdam, Netherlands.
[Oldenburg, Rogier A.; van den Ouweland, Ans M. W.] Erasmus Univ, Dept Clin Genet, Family Canc Clin, Med Ctr, Rotterdam, Netherlands.
[Cox, Angela] Univ Sheffield, Dept Oncol, Inst Canc Studies, Sheffield, S Yorkshire, England.
[Reed, Malcolm W. R.] Univ Sheffield, Acad Unit Surg Oncol, Dept Oncol, Sheffield, S Yorkshire, England.
[Jakubowska, Ania; Lubinski, Jan; Jaworska, Katarzyna; Durda, Katarzyna] Pomeranian Med Univ, Int Hereditary Canc Ctr, Dept Genet & Pathol, Szczecin, Poland.
[Beesley, Jonathan; Chen, Xiaoqing; Chenevix-Trench, Georgia] Queensland Inst Med Res, Brisbane, Qld 4006, Australia.
[Muir, Kenneth R.; Lophatananon, Artitaya] Univ Warwick, Warwick Med Sch, Coventry CV4 7AL, W Midlands, England.
[Rattanamongkongul, Suthee] Srinakharainwirot Univ, Dept Prevent Med, Ongkharak, Thailand.
[Chaiwerawattana, Arkom] Minist Publ Hlth, Natl Canc Inst Thailand, Dept Acad Support, Bangkok, Thailand.
[Kang, Daehee; Yoo, Keun-Young; Noh, Dong-Young] Seoul Natl Univ, Coll Med, Dept Prevent Med, Seoul, South Korea.
[Shen, Chen-Yang; Wu, Pei-Ei; Hsiung, Chia-Ni] Acad Sinica, Inst Biomed Sci, Taipei, Taiwan.
[Yu, Jyh-Cherng] Triserv Gen Hosp, Dept Surg, Taipei, Taiwan.
[Perkins, Annie; Swann, Ruth; Velentzis, Louiza] Univ Westminster, Breast Canc Res Grp, Dept Mol & Appl Biosci, London W1R 8AL, England.
[Eccles, Diana M.; Tapper, Will J.; Gerty, Susan M.; Graham, Nikki J.] Univ Southampton, Fac Med, Southampton SO9 5NH, Hants, England.
[Ponder, Bruce A. J.] Univ Cambridge, Dept Oncol, Cambridge, England.
[Ponder, Bruce A. J.] Canc Res UK CRUK Cambridge Res Inst, Cambridge, England.
[Lathrop, Mark] Ctr Natl Genotypage, Evry, France.
[Lathrop, Mark] CEPH, Fdn Jean Dausset, Paris, France.
RP Easton, DF (reprint author), Univ Cambridge, Dept Oncol, Ctr Canc Genet Epidemiol, Cambridge, England.
EM douglas@srl.cam.ac.uk
RI Rahman, Nazneen/D-2802-2013; Gonzalez-Neira, Anna/C-5791-2015;
Garcia-Closas, Montserrat /F-3871-2015; Brinton, Louise/G-7486-2015;
Hartikainen, Jaana/E-6256-2015; Bowtell, David/H-1007-2016; Bruning,
Thomas/G-8120-2015; Khusnutdinova, Elza/A-4810-2013; Brenner,
Hermann/B-4627-2017; manoukian, siranoush/E-7132-2017; Dzhemileva,
Lilya/K-8636-2013; Dork, Thilo/J-8620-2012; Jakubowska,
Anna/O-8050-2014; Shen, CY/F-6271-2010; Verdrengh, Evelien/H-4571-2012;
Noh, Dong-Young/G-5531-2011; Kang, Dae Hee/E-8631-2012; Yoo,
Keun-Young/J-5548-2012; truong, therese/A-2837-2013; Muller-Myhsok,
Bertram/A-3289-2013; Kerin, Michael/D-6748-2013; Ekici,
Arif/C-3971-2013; Andrulis, Irene/E-7267-2013
OI Giles, Graham/0000-0003-4946-9099; Arndt, Volker/0000-0001-9320-8684;
Rahman, Nazneen/0000-0003-4376-0440; Schoemaker,
Minouk/0000-0001-8403-2234; Lux, Michael Patrick/0000-0002-2781-2178;
Lissowska, Jolanta/0000-0003-2695-5799; Dunning, Alison
Margaret/0000-0001-6651-7166; Rivadeneira, Fernando/0000-0001-9435-9441;
Nevanlinna, Heli/0000-0002-0916-2976; dos Santos Silva,
Isabel/0000-0002-6596-8798; Cox, Angela/0000-0002-5138-1099; Bui,
Minh/0000-0002-9099-6870; Park, Daniel/0000-0002-6354-0931;
Garcia-Closas, Montserrat /0000-0003-1033-2650; Brinton,
Louise/0000-0003-3853-8562; Bowtell, David/0000-0001-9089-7525; Bruning,
Thomas/0000-0001-9560-5464; Brenner, Hermann/0000-0002-6129-1572;
manoukian, siranoush/0000-0002-6034-7562; Fortuzzi,
Stefano/0000-0002-5662-3800; Hollestelle,
Antoinette/0000-0003-1166-1966; Dennis, Joe/0000-0003-4591-1214; Czene,
Kamila/0000-0002-3233-5695; Dzhemileva, Lilya/0000-0003-3315-4746;
FU Cancer Research UK [A10710, 10118, 10124]; Medical Research Council
[G0700491]; NCI NIH HHS [R25 CA092049]; Wellcome Trust [090532]
NR 67
TC 135
Z9 139
U1 4
U2 65
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1061-4036
J9 NAT GENET
JI Nature Genet.
PD MAR
PY 2012
VL 44
IS 3
BP 312
EP U120
DI 10.1038/ng.1049
PG 8
WC Genetics & Heredity
SC Genetics & Heredity
GA 899VC
UT WOS:000300843600018
PM 22267197
ER
PT J
AU Postel-Vinay, S
Veron, AS
Tirode, F
Pierron, G
Reynaud, S
Kovar, H
Oberlin, O
Lapouble, E
Ballet, S
Lucchesi, C
Kontny, U
Gonzalez-Neira, A
Picci, P
Alonso, J
Patino-Garcia, A
de Paillerets, BB
Laud, K
Dina, C
Froguel, P
Clavel-Chapelon, F
Doz, F
Michon, J
Chanock, SJ
Thomas, G
Cox, DG
Delattre, O
AF Postel-Vinay, Sophie
Veron, Amelie S.
Tirode, Franck
Pierron, Gaelle
Reynaud, Stephanie
Kovar, Heinrich
Oberlin, Odile
Lapouble, Eve
Ballet, Stelly
Lucchesi, Carlo
Kontny, Udo
Gonzalez-Neira, Anna
Picci, Piero
Alonso, Javier
Patino-Garcia, Ana
de Paillerets, Brigitte Bressac
Laud, Karine
Dina, Christian
Froguel, Philippe
Clavel-Chapelon, Francoise
Doz, Francois
Michon, Jean
Chanock, Stephen J.
Thomas, Gilles
Cox, David G.
Delattre, Olivier
TI Common variants near TARDBP and EGR2 are associated with susceptibility
to Ewing sarcoma
SO NATURE GENETICS
LA English
DT Article
ID GENOME-WIDE ASSOCIATION; TUMORS; RISK; DISEASE; CANCER; TRANSLOCATION;
PATHOGENESIS; EXPRESSION; SIBLINGS; FUSION
AB Ewing sarcoma, a pediatric tumor characterized by EWSR1-ETS fusions, is predominantly observed in populations of European ancestry. We performed a genome-wide association study (GWAS) of 401 French individuals with Ewing sarcoma, 684 unaffected French individuals and 3,668 unaffected individuals of European descent and living in the United States. We identified candidate risk loci at 1p36.22, 10q21 and 15q15. We replicated these loci in two independent sets of cases and controls. Joint analysis identified associations with rs9430161 (P = 1.4 x 10(-20); odds ratio (OR) = 2.2) located 25 kb upstream of TARDBP, rs224278 (P = 4.0 x 10(-17); OR = 1.7) located 5 kb upstream of EGR2 and, to a lesser extent, rs4924410 at 15q15 (P = 6.6 x 10(-9); OR = 1.5). The major risk haplotypes were less prevalent in Africans, suggesting that these loci could contribute to geographical differences in Ewing sarcoma incidence. TARDBP shares structural similarities with EWSR1 and FUS, which encode RNA binding proteins, and EGR2 is a target gene of EWSR1-ETS. Variants at these loci were associated with expression levels of TARDBP, ADO (encoding cysteamine dioxygenase) and EGR2.
C1 [Postel-Vinay, Sophie; Tirode, Franck; Lucchesi, Carlo; Laud, Karine; Delattre, Olivier] Inst Curie, INSERM, Genet & Biol Canc U830, Paris, France.
[Postel-Vinay, Sophie; Tirode, Franck; Lucchesi, Carlo; Laud, Karine; Delattre, Olivier] Inst Curie, Ctr Rech, Paris, France.
[Veron, Amelie S.; Thomas, Gilles; Cox, David G.] Canc Res Ctr Lyon, INSERM, U1052, Leon Berard Canc Ctr, Lyon, France.
[Pierron, Gaelle; Reynaud, Stephanie; Lapouble, Eve; Ballet, Stelly; Delattre, Olivier] Ctr Hosp, Inst Curie, Unite Genet Somat, Paris, France.
[Kovar, Heinrich] St Anna Childrens Hosp, Childrens Canc Res Inst, A-1090 Vienna, Austria.
[Oberlin, Odile] Inst Gustave Roussy, Serv Pediat, Villejuif, France.
[Kontny, Udo] Univ Freiburg Klinikum, Zentrum Kinder & Jugendmed, Freiburg, Germany.
[Gonzalez-Neira, Anna] Spanish Natl Canc Res Ctr, Human Genotyping Unit CeGen, Human Canc Genet Programme, Madrid, Spain.
[Picci, Piero] Ist Ortoped Rizzoli Bologna, Lab Oncol Sperimentale, Bologna, Italy.
[Alonso, Javier] Inst Salud Carlos III, Unidad Tumores Solidos Infantiles, Majadahonda, Spain.
[Patino-Garcia, Ana] Univ Navarra, Univ Clin, Lab Pediat, E-31080 Pamplona, Spain.
[de Paillerets, Brigitte Bressac] Inst Gustave Roussy, Serv Genet, Villejuif, France.
[Dina, Christian] IRI UN, INSERM, U915, Inst Thorax, Nantes, France.
[Froguel, Philippe] Univ London Imperial Coll Sci Technol & Med, Sch Publ Hlth, London, England.
[Clavel-Chapelon, Francoise] Inst Gustave Roussy, Ctr Natl Rech Sci, Unite Mixtre Rech 1018, Villejuif, France.
[Doz, Francois] Univ Paris 05, Paris, France.
[Doz, Francois; Michon, Jean] Ctr Hosp, Dept Pediat, Inst Curie, Paris, France.
[Chanock, Stephen J.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA.
[Thomas, Gilles] Synergie Lyon Canc, Lyon, France.
RP Delattre, O (reprint author), Inst Curie, INSERM, Genet & Biol Canc U830, Paris, France.
EM olivier.delattre@curie.fr
RI Cox, David/A-2023-2009; Tirode, Franck/B-4586-2009; Patino-Garcia,
Ana/I-4299-2012; Doz, Francois/K-8616-2012; Clavel-Chapelon,
Francoise/G-6733-2014; Gonzalez-Neira, Anna/C-5791-2015; Dina,
Christian/D-3535-2015; Alonso, Javier/B-6012-2013; Picci,
Piero/J-5979-2016
OI Cox, David/0000-0002-2152-9259; Tirode, Franck/0000-0003-4731-7817;
Dina, Christian/0000-0002-7722-7348; Alonso, Javier/0000-0002-6287-8391;
Kovar, Heinrich/0000-0001-6873-9109; Picci, Piero/0000-0002-8519-4101
FU Institut Curie; Inserm; Ligue Nationale Contre le Cancer; Region Ile de
France; Institut National du Cancer [2008-044, 0627, ZP09-027-EPI];
Synergie Lyon Cancer foundation; KCK; European Embryonal Tumor (EET)
pipeline programs; Societe Francaise des Cancers de l'Enfant; Spanish
Ministry of Science and Technology [SAF2009-10158]; Fundacion de la
Asociacion Espanola Contra el Cancer; Fundacion Maria Francisca de
Roviralta; Sociedad Espanola de Hematologia y Oncologia Pediatricas;
Courir pour Mathieu; Dans les pas du Geant; Olivier Chape; Les
Bagouzamanon; Enfants et Sante; les Amis de Claire
FX We thank E. Thomas from Synergie Lyon Cancer for advice on statistical
methods. We thank the staff from the Integragen Company for excellent
service and V. Chene for outstanding assistance. We thank the following
clinicians for providing samples used in this work: C. Alenda, F.
Almazan, D. Ansoborlo, L. Aymerich, L. Benboukbher, C. Belendez, C.
Berger, C. Bergeron, P. Biron, J. Y. Blay, E. Bompas, H. Bonnefoi, P.
Boutard, B. Bui-Nguyen, D. Chauveaux, C. Calvo, A. Carbone, C. Clement,
T. Contra, N. Corradini, A. S. Defachelles, V. Gendemer-Delignieres, A.
Deville, A. Echevarria, J. Fayette, M. Fraga, D. Frappaz, J. L. Fuster,
P. Garcia-Miguel, J. C. Gentet, P. Kerbrat, V. Laithier, V. Laurence, P.
Leblond, O. Lejars, R. Lopez-Almaraz, B. Lopez-Ibor, P. Lutz, J. F.
Mallet, L. Mansuy, P. Marec Berard, G. Margueritte, A. Marie Cardine, C.
Melero, L. Mignot, F. Millot, O. Minckes, G. Margueritte, C. Mata, M. E.
Mateos, M. Melo, C. Moscardo, M. Munzer, B. Narciso, A. Navajas, D.
Orbach, C. Oudot, H. Pacquement, C. Paillard, Y. Perel, T. Philip, C.
Piguet, M. I. Pintor, D. Plantaz, E. Plouvier, S. Ramirez-Del-Villar, I.
Ray-Coquard, Y. Reguerre, M. Rios, P. Rohrlich, H. Rubie, A. Sastre, G.
Schleiermacher, C. Schmitt, P. Schneider, L. Sierrasesumaga, C. Soler,
N. Sirvent, S. Taque, E. Thebaud, A. Thyss, R. Tichit, J. J. Uriz, J. P.
Vannier, F. Watelle-Pichon. We also thank the European Prospective
Investigation into Cancer and Nutrition (EPIC) Steering Committee (E.
Riboli, Principal Investigator) for access to genotype data from the
EPIC cohorts and the Children's Cancer and Leukaemia Group (CCLG) Tissue
Bank (funded by Cancer Research UK) for access to specimens. This work
was supported by grants from the Institut Curie, the Inserm, the Ligue
Nationale Contre le Cancer (Equipe labellisee, Carte d'Identite des
Tumeurs program and Recherche Epidemiologique 2009 program), the Region
Ile de France, the Institut National du Cancer (2008-044, 0627 and
ZP09-027-EPI), the Synergie Lyon Cancer foundation, the KCK and European
Embryonal Tumor (EET) pipeline programs, the Societe Francaise des
Cancers de l'Enfant, the Spanish Ministry of Science and Technology
(SAF2009-10158), the Fundacion de la Asociacion Espanola Contra el
Cancer, the Fundacion Maria Francisca de Roviralta and the Sociedad
Espanola de Hematologia y Oncologia Pediatricas and the following
associations: Courir pour Mathieu, Dans les pas du Geant, Olivier Chape,
Les Bagouzamanon, Enfants et Sante and les Amis de Claire.
NR 35
TC 43
Z9 43
U1 1
U2 10
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1061-4036
J9 NAT GENET
JI Nature Genet.
PD MAR
PY 2012
VL 44
IS 3
BP 323
EP U133
DI 10.1038/ng.1085
PG 7
WC Genetics & Heredity
SC Genetics & Heredity
GA 899VC
UT WOS:000300843600020
PM 22327514
ER
PT J
AU Bellenguez, C
Bevan, S
Gschwendtner, A
Spencer, CCA
Burgess, AI
Pirinen, M
Jackson, CA
Traylor, M
Strange, A
Su, Z
Band, G
Syme, PD
Malik, R
Pera, J
Norrving, B
Lemmens, R
Freeman, C
Schanz, R
James, T
Poole, D
Murphy, L
Segal, H
Cortellini, L
Cheng, YC
Woo, D
Nalls, MA
Muller-Myhsok, B
Meisinger, C
Seedorf, U
Ross-Adams, H
Boonen, S
Wloch-Kopec, D
Valant, V
Slark, J
Furie, K
Delavaran, H
Langford, C
Deloukas, P
Edkins, S
Hunt, S
Gray, E
Dronov, S
Peltonen, L
Gretarsdottir, S
Thorleifsson, G
Thorsteinsdottir, U
Stefansson, K
Boncoraglio, GB
Parati, EA
Attia, J
Holliday, E
Levi, C
Franzosi, MG
Goel, A
Helgadottir, A
Blackwell, JM
Bramon, E
Brown, MA
Casas, JP
Corvin, A
Duncanson, A
Jankowski, J
Mathew, CG
Palmer, CNA
Plomin, R
Rautanen, A
Sawcer, SJ
Trembath, RC
Viswanathan, AC
Wood, NW
Worrall, BB
Kittner, SJ
Mitchell, BD
Kissela, B
Meschia, JF
Thijs, V
Lindgren, A
Macleod, MJ
Slowik, A
Walters, M
Rosand, J
Sharma, P
Farrall, M
Sudlow, CLM
Rothwell, PM
Dichgans, M
Donnelly, P
Markus, HS
AF Bellenguez, Celine
Bevan, Steve
Gschwendtner, Andreas
Spencer, Chris C. A.
Burgess, Annette I.
Pirinen, Matti
Jackson, Caroline A.
Traylor, Matthew
Strange, Amy
Su, Zhan
Band, Gavin
Syme, Paul D.
Malik, Rainer
Pera, Joanna
Norrving, Bo
Lemmens, Robin
Freeman, Colin
Schanz, Renata
James, Tom
Poole, Deborah
Murphy, Lee
Segal, Helen
Cortellini, Lynelle
Cheng, Yu-Ching
Woo, Daniel
Nalls, Michael A.
Mueller-Myhsok, Bertram
Meisinger, Christa
Seedorf, Udo
Ross-Adams, Helen
Boonen, Steven
Wloch-Kopec, Dorota
Valant, Valerie
Slark, Julia
Furie, Karen
Delavaran, Hossein
Langford, Cordelia
Deloukas, Panos
Edkins, Sarah
Hunt, Sarah
Gray, Emma
Dronov, Serge
Peltonen, Leena
Gretarsdottir, Solveig
Thorleifsson, Gudmar
Thorsteinsdottir, Unnur
Stefansson, Kari
Boncoraglio, Giorgio B.
Parati, Eugenio A.
Attia, John
Holliday, Elizabeth
Levi, Chris
Franzosi, Maria-Grazia
Goel, Anuj
Helgadottir, Anna
Blackwell, Jenefer M.
Bramon, Elvira
Brown, Matthew A.
Casas, Juan P.
Corvin, Aiden
Duncanson, Audrey
Jankowski, Janusz
Mathew, Christopher G.
Palmer, Colin N. A.
Plomin, Robert
Rautanen, Anna
Sawcer, Stephen J.
Trembath, Richard C.
Viswanathan, Ananth C.
Wood, Nicholas W.
Worrall, Bradford B.
Kittner, Steven J.
Mitchell, Braxton D.
Kissela, Brett
Meschia, James F.
Thijs, Vincent
Lindgren, Arne
Macleod, Mary Joan
Slowik, Agnieszka
Walters, Matthew
Rosand, Jonathan
Sharma, Pankaj
Farrall, Martin
Sudlow, Cathie L. M.
Rothwell, Peter M.
Dichgans, Martin
Donnelly, Peter
Markus, Hugh S.
CA ISGC
WTCCC2
TI Genome-wide association study identifies a variant in HDAC9 associated
with large vessel ischemic stroke
SO NATURE GENETICS
LA English
DT Article
ID ATRIAL-FIBRILLATION; HISTONE DEACETYLASES; SUSCEPTIBILITY LOCI;
ALGORITHM; GENETICS; DISEASE; SIGNALS; ROLES; RISK
AB Genetic factors have been implicated in stroke risk, but few replicated associations have been reported. We conducted a genome-wide association study (GWAS) for ischemic stroke and its subtypes in 3,548 affected individuals and 5,972 controls, all of European ancestry. Replication of potential signals was performed in 5,859 affected individuals and 6,281 controls. We replicated previous associations for cardioembolic stroke near PITX2 and ZFHX3 and for large vessel stroke at a 9p21 locus. We identified a new association for large vessel stroke within HDAC9 (encoding histone deacetylase 9) on chromosome 7p21.1 (including further replication in an additional 735 affected individuals and 28,583 controls) (rs11984041; combined P = 1.87 x 10(-11); odds ratio (OR) = 1.42, 95% confidence interval (CI) = 1.28-1.57). All four loci exhibited evidence for heterogeneity of effect across the stroke subtypes, with some and possibly all affecting risk for only one subtype. This suggests distinct genetic architectures for different stroke subtypes.
C1 [Bellenguez, Celine; Spencer, Chris C. A.; Pirinen, Matti; Strange, Amy; Su, Zhan; Band, Gavin; Freeman, Colin; Goel, Anuj; Helgadottir, Anna; Rautanen, Anna; Farrall, Martin; Donnelly, Peter] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.
[Bevan, Steve; Traylor, Matthew; James, Tom; Markus, Hugh S.] St Georges Univ London, Stroke & Dementia Res Grp, London, England.
[Gschwendtner, Andreas; Malik, Rainer; Dichgans, Martin] Univ Munich, Univ Munchen Klinikum, Inst Stroke & Dementia Res, Munich, Germany.
[Burgess, Annette I.; Poole, Deborah; Segal, Helen; Rothwell, Peter M.] Univ Oxford, Nuffield Dept Clin Neurosci, Stroke Prevent Res Unit, Oxford, England.
[Jackson, Caroline A.; Sudlow, Cathie L. M.] Univ Edinburgh, Div Clin Neurosci, Edinburgh, Midlothian, Scotland.
[Syme, Paul D.; Macleod, Mary Joan] Univ Aberdeen, Div Appl Med, Aberdeen, Scotland.
[Pera, Joanna; Ross-Adams, Helen; Wloch-Kopec, Dorota; Slowik, Agnieszka] Jagiellonian Univ, Coll Med, Dept Neurol, Krakow, Poland.
[Norrving, Bo; Delavaran, Hossein; Lindgren, Arne] Lund Univ, Dept Clin Sci, Lund, Sweden.
[Norrving, Bo; Delavaran, Hossein; Lindgren, Arne] Skane Univ Hosp, Dept Neurol, Lund, Sweden.
[Lemmens, Robin; Thijs, Vincent] Univ Hosp Leuven, Dept Neurol, Louvain, Belgium.
[Lemmens, Robin; Thijs, Vincent] VIB, Vesalius Res Ctr, Louvain, Belgium.
[Schanz, Renata; Slark, Julia; Sharma, Pankaj] Univ London Imperial Coll Sci Technol & Med, ICCRU, London, England.
[Murphy, Lee] Univ Edinburgh, Western Gen Hosp, Wellcome Trust Clin Res Facil Genet Core Lab, Edinburgh, Midlothian, Scotland.
[Cortellini, Lynelle; Valant, Valerie; Furie, Karen; Rosand, Jonathan] Massachusetts Gen Hosp, Dept Neurol, Ctr Human Genet Res, Boston, MA 02114 USA.
[Cortellini, Lynelle; Valant, Valerie; Rosand, Jonathan] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA.
[Cheng, Yu-Ching; Mitchell, Braxton D.] Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA.
[Cheng, Yu-Ching; Mitchell, Braxton D.] Univ Maryland, Sch Med, Dept Epidemiol & Publ Hlth, Baltimore, MD 21201 USA.
[Woo, Daniel; Kissela, Brett] Univ Cincinnati, Coll Med, Dept Neurol, Cincinnati, OH USA.
[Nalls, Michael A.] NIA, Neurogenet Lab, Intramural Res Program, Bethesda, MD 20892 USA.
[Mueller-Myhsok, Bertram] Max Planck Inst Psychiat, D-80804 Munich, Germany.
[Meisinger, Christa] German Res Ctr Environm Hlth, Inst Epidemiol 2, Helmholtz Zentrum Munchen, Neuherberg, Germany.
[Seedorf, Udo] Univ Munster, Leibniz Inst Arterioskleroseforsch, Munster, Germany.
[Boonen, Steven] Univ Hosp Leuven, Div Geriatr Med, Louvain, Belgium.
[Langford, Cordelia; Deloukas, Panos; Edkins, Sarah; Hunt, Sarah; Gray, Emma; Dronov, Serge; Peltonen, Leena] Wellcome Trust Sanger Inst, Cambridge, England.
[Gretarsdottir, Solveig; Thorleifsson, Gudmar; Thorsteinsdottir, Unnur; Stefansson, Kari; Helgadottir, Anna] deCODE Genet, Reykjavik, Iceland.
[Thorsteinsdottir, Unnur; Stefansson, Kari] Univ Iceland, Fac Med, Reykjavik, Iceland.
[Boncoraglio, Giorgio B.; Parati, Eugenio A.] Fdn Ist Ricovero & Cura Carattere Sci IRCCS, Ist Neurol Carlo Besta, Milan, Italy.
[Attia, John; Holliday, Elizabeth; Levi, Chris] Univ Newcastle, Hunter Med Res Inst, Ctr Brain & Mental Hlth Res, Newcastle, NSW 2300, Australia.
[Franzosi, Maria-Grazia] Ist Ric Farmacol Mario Negri, Dept Cardiovasc Res, Milan, Italy.
[Goel, Anuj; Helgadottir, Anna; Farrall, Martin] Univ Oxford, Dept Cardiovasc Med, Oxford, England.
[Blackwell, Jenefer M.] Univ Western Australia, Ctr Child Hlth Res, Perth, WA, Australia.
[Blackwell, Jenefer M.] Univ Cambridge, Sch Clin Med, Cambridge Inst Med Res, Cambridge, England.
[Bramon, Elvira] Kings Coll London, Inst Psychiat, Biomed Res Ctr Mental Hlth, Div Psychol Med & Psychiat, London WC2R 2LS, England.
[Brown, Matthew A.] Univ Queensland, Princess Alexandra Hosp, Diamantina Inst, Brisbane, Qld, Australia.
[Casas, Juan P.] London Sch Hyg & Trop Med, Dept Epidemiol & Populat Hlth, London WC1, England.
[Casas, Juan P.] UCL, Dept Epidemiol & Publ Hlth, London, England.
[Corvin, Aiden] Trinity Coll Dublin, Inst Mol Med, Neuropsychiat Genet Res Grp, Dublin, Ireland.
[Duncanson, Audrey] Wellcome Trust Res Labs, London, England.
[Jankowski, Janusz] Barts & London Queen Marys Sch Med & Dent, Ctr Gastroenterol, London, England.
[Jankowski, Janusz] Univ Oxford, Div Clin Pharmacol, Oxford, England.
[Mathew, Christopher G.; Trembath, Richard C.] Kings Coll London, Guys Hosp, Sch Med, Dept Med & Mol Genet, London WC2R 2LS, England.
[Palmer, Colin N. A.] Univ Dundee, Ninewells Hosp & Med Sch, Biomed Res Ctr, Dundee DD1 9SY, Scotland.
[Plomin, Robert] Kings Coll London, Inst Psychiat, Social Genet & Dev Psychiat Ctr, London WC2R 2LS, England.
[Sawcer, Stephen J.] Univ Cambridge, Addenbrookes Hosp, Dept Clin Neurosci, Cambridge CB2 2QQ, England.
[Viswanathan, Ananth C.] Natl Hlth Serv NHS Fdn Trust, Moorfields Eye Hosp, Biomed Res Ctr Ophthalmol, Natl Inst Hlth Res NIHR, London, England.
[Viswanathan, Ananth C.] UCL, Inst Ophthalmol, London, England.
[Wood, Nicholas W.] UCL, Inst Neurol, Dept Mol Neuroscience, London, England.
[Worrall, Bradford B.] Univ Virginia, Sch Med, Dept Neurol, Charlottesville, VA 22908 USA.
[Worrall, Bradford B.] Univ Virginia, Sch Med, Dept Publ Hlth Sci, Charlottesville, VA 22908 USA.
[Kittner, Steven J.] Univ Maryland, Sch Med, Dept Neurol, Baltimore, MD 21201 USA.
[Kittner, Steven J.] Baltimore Vet Affairs Med Ctr, Baltimore Geriatr Res Educ & Clin Ctr, Baltimore, MD USA.
[Meschia, James F.] Mayo Clin, Dept Neurol, Jacksonville, FL 32224 USA.
[Walters, Matthew] Univ Glasgow, Inst Cardiovasc & Med Sci, Glasgow, Lanark, Scotland.
[Donnelly, Peter] Univ Oxford, Dept Stat, Oxford OX1 3TG, England.
RP Donnelly, P (reprint author), Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England.
EM peter.donnelly@well.ox.ac.uk; hmarkus@sgul.ac.uk
RI Muller-Myhsok, Bertram/A-3289-2013; Deloukas, Panos/B-2922-2013; Attia,
John/F-5376-2013; Jackson, Caroline/B-5954-2012; Meisinger,
Christine/B-5358-2014; Wood, Nicholas/C-2505-2009; Jankowski,
Janusz/H-2706-2012; Blackwell, Jenefer/H-3015-2015; Mathew,
Christopher/G-3434-2015; Study, GoDARTS/K-9448-2016; Boncoraglio,
Giorgio/B-8647-2011; Palmer, Colin/C-7053-2008; Thijs,
Vincent/C-3647-2009
OI Macleod, Mary Joan/0000-0003-2115-8184; Pirinen,
Matti/0000-0002-1664-1350; Plomin, Robert/0000-0002-0756-3629; Bevan,
Steve/0000-0003-0490-6830; Trembath, Richard/0000-0003-0550-3400;
Meisinger, Christa/0000-0002-9026-6544; Mitchell,
Braxton/0000-0003-4920-4744; Kissela, Brett/0000-0002-9773-4013;
Seedorf, Udo/0000-0003-4652-5358; Murphy, Lee/0000-0001-6467-7449;
Corvin, Aiden/0000-0001-6717-4089; Norrving, Bo/0000-0002-8024-5096;
Hunt, Sarah/0000-0002-8350-1235; Brown, Matthew A/0000-0003-0538-8211;
Traylor, Matthew/0000-0001-6624-8621; Deloukas,
Panos/0000-0001-9251-070X; Attia, John/0000-0001-9800-1308; Jackson,
Caroline/0000-0002-2067-2811; Wood, Nicholas/0000-0002-9500-3348;
Jankowski, Janusz/0000-0003-2130-9181; Mathew,
Christopher/0000-0003-4178-1838; Palmer, Colin/0000-0002-6415-6560;
Thijs, Vincent/0000-0002-6614-8417
FU Medical Research Council [G0000934]; Wellcome Trust [068545/Z/02,
085475/B/08/Z, 085475/Z/08/Z, WT084724MA, WTCCC2]
FX We thank S. Bertrand, J. Bryant, S. L. Clark, J. S. Conquer, T. Dibling,
J. C. Eldred, S. Gamble, C. Hind, M. L. Perez, C. R. Stribling, S.
Taylor and A. Wilk of the Wellcome Trust Sanger Institute's Sample and
Genotyping Facilities for technical assistance. We acknowledge use of
the British 1958 Birth Cohort DNA collection, which is funded by the
Medical Research Council (G0000934) and the Wellcome Trust
(068545/Z/02), and of the UK National Blood Service controls funded by
the Wellcome Trust. We thank W. Bodmer and B. Winney for use of the
People of the British Isles DNA collection, which was funded by the
Wellcome Trust. We thank the following individuals who contributed to
collection, phenotyping, sample processing and data management for the
different cohorts: A. Burgess, A. Syed and N. Paul (Oxford Vascular
Study); M. Dennis, P. Sandercock, C. Warlow, S. Hart, S. Keir, J.
Wardlaw, A. Farrall, G. Potter, A. Hutchison and M. McDowall (Edinburgh
Stroke Study); A. Pasdar and H. Clinkscale (Aberdeen); P. Higgins
(Glasgow); T. G. Brott, R. D. Brown, S. Silliman, M. Frankel, D. Case,
S. Rich, J. Hardy, A. Singleton (ISGS); M. J. Sparks, K. Ryan, J. Cole,
M. Wozniak, B. Stern, R. Wityk, C. Johnson and D. Buchholz (GEOS); and
J. Maguire, S. Koblar, J. Golledge, J. Surm, G. Hankey, J. Jannes, M.
Lewis, R. Scott, L. Lincz; P. Moscato and R. Baker (Australian Stroke
Genetics Collaborative membership). The principal funding for this study
was provided by the Wellcome Trust as part of the WTCCC2 project
(085475/B/08/Z, 085475/Z/08/Z and WT084724MA). For details of other
funding support, see the Supplementary Note.
NR 30
TC 153
Z9 155
U1 2
U2 20
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1061-4036
J9 NAT GENET
JI Nature Genet.
PD MAR
PY 2012
VL 44
IS 3
BP 328
EP U141
DI 10.1038/ng.1081
PG 8
WC Genetics & Heredity
SC Genetics & Heredity
GA 899VC
UT WOS:000300843600021
ER
PT J
AU Angermann, BR
Klauschen, F
Garcia, AD
Prustel, T
Zhang, FK
Germain, RN
Meier-Schellersheim, M
AF Angermann, Bastian R.
Klauschen, Frederick
Garcia, Alex D.
Prustel, Thorsten
Zhang, Fengkai
Germain, Ronald N.
Meier-Schellersheim, Martin
TI Computational modeling of cellular signaling processes embedded into
dynamic spatial contexts
SO NATURE METHODS
LA English
DT Article
ID FUS3 MAP KINASE; MATING PATHWAY; ADHESION; YEAST; PROTEIN; DIFFUSION;
TRANSDUCTION; ACTIVATION; NETWORKS; BIOLOGY
AB Cellular signaling processes depend on spatiotemporal distributions of molecular components. Multicolor, high-resolution microscopy permits detailed assessment of such distributions, providing input for fine-grained computational models that explore mechanisms governing dynamic assembly of multimolecular complexes and their role in shaping cellular behavior. However, it is challenging to incorporate into such models both complex molecular reaction cascades and the spatial localization of signaling components in dynamic cellular morphologies. Here we introduce an approach to address these challenges by automatically generating computational representations of complex reaction networks based on simple bimolecular interaction rules embedded into detailed, adaptive models of cellular morphology. Using examples of receptor-mediated cellular adhesion and signal-induced localized mitogen-activated protein kinase (MAPK) activation in yeast, we illustrate the capacity of this simulation technique to provide insights into cell biological processes. The modeling algorithms, implemented in a new version of the Simmune toolset, are accessible through intuitive graphical interfaces and programming libraries.
C1 [Angermann, Bastian R.; Klauschen, Frederick; Garcia, Alex D.; Prustel, Thorsten; Zhang, Fengkai; Germain, Ronald N.; Meier-Schellersheim, Martin] NIAID, Lab Syst Biol, NIH, Bethesda, MD 20892 USA.
[Klauschen, Frederick] Charite, Inst Pathol, D-13353 Berlin, Germany.
RP Angermann, BR (reprint author), NIAID, Lab Syst Biol, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM bastian.angermann@nih.gov; mms@niaid.nih.gov
RI Klauschen, Frederick/C-5637-2015
FU US National Institute of Allergy and Infectious Diseases of the National
Institutes of Health
FX We thank R. Schwartz, R. Varma, A. Nita-Lazar, I. Fraser, J. Tsang and
D. Cioffi for helpful comments, members of the Laboratory for Systems
Biology at the US National Institute of Allergy and Infectious Diseases
for insightful discussions, G. Mack for advice during the early stages
of Simmune development and A. Meier-Schellersheim for creating Figure 2
and Supplementary Figure 1. This work was supported by the Intramural
Research Program of the US National Institute of Allergy and Infectious
Diseases of the National Institutes of Health.
NR 35
TC 43
Z9 43
U1 1
U2 20
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1548-7091
J9 NAT METHODS
JI Nat. Methods
PD MAR
PY 2012
VL 9
IS 3
BP 283
EP U95
DI 10.1038/NMETH.1861
PG 10
WC Biochemical Research Methods
SC Biochemistry & Molecular Biology
GA 900ME
UT WOS:000300890400026
PM 22286385
ER
PT J
AU Sims, JJ
Scavone, F
Cooper, EM
Kane, LA
Youle, RJ
Boeke, JD
Cohen, RE
AF Sims, Joshua J.
Scavone, Francesco
Cooper, Eric M.
Kane, Lesley A.
Youle, Richard J.
Boeke, Jef D.
Cohen, Robert E.
TI Polyubiquitin-sensor proteins reveal localization and linkage-type
dependence of cellular ubiquitin signaling
SO NATURE METHODS
LA English
DT Article
ID K11-LINKED POLYUBIQUITINATION; DNA-REPAIR; BINDING; CHAINS; TNF;
DEGRADATION; CELLS; MULTIUBIQUITINATION; P62/SQSTM1; ACTIVATION
AB Polyubiquitin chain topology is thought to direct modified substrates to specific fates, but this function-topology relationship is poorly understood, as are the dynamics and subcellular locations of specific polyubiquitin signals. Experimental access to these questions has been limited because linkage-specific inhibitors and in vivo sensors have been unavailable. Here we present a general strategy to track linkage-specific polyubiquitin signals in yeast and mammalian cells, and to probe their functions. We designed several high-affinity Lys63 polyubiquitin-binding proteins and demonstrate their specificity in vitro and in cells. We apply these tools as competitive inhibitors to dissect the polyubiquitin-linkage dependence of NF-kappa B activation in several cell types, inferring the essential role of Lys63 polyubiquitin for signaling via the IL-1 beta and TNF-related weak inducer of apoptosis (TWEAK) but not TNF-alpha receptors. We anticipate live-cell imaging, proteomic and biochemical applications for these tools and extension of the design strategy to other polymeric ubiquitin-like protein modifications.
C1 [Sims, Joshua J.; Cohen, Robert E.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Biochem & Mol Biol, Baltimore, MD USA.
[Scavone, Francesco; Cohen, Robert E.] Colorado State Univ, Dept Biochem & Mol Biol, Ft Collins, CO 80523 USA.
[Cooper, Eric M.; Boeke, Jef D.] Johns Hopkins Univ, Sch Med, Dept Mol Biol & Genet, Baltimore, MD 21205 USA.
[Cooper, Eric M.; Boeke, Jef D.] Johns Hopkins Univ, Sch Med, High Throughput Biol Ctr, Baltimore, MD 21205 USA.
[Kane, Lesley A.; Youle, Richard J.] Natl Inst Neurol Disorders & Stroke, Biochem Sect, Surg Neurol Branch, US Natl Inst Hlth, Bethesda, MD USA.
RP Cohen, RE (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Dept Biochem & Mol Biol, Baltimore, MD USA.
EM joshua_sims@hms.harvard.edu; bob.cohen@colostate.edu
OI Boeke, Jef/0000-0001-5322-4946
FU Damon Runyon Cancer Research Foundation (DRG) [2073-11]; US National
Institutes of Health (NIH) [RR020839]; NIH [P01 CA139980, RC1 GM091424,
1R01 GM097452]; US National Institute of Neurologial Disorders and
Stroke
FX We thank S. Beese-Sims for constructing the leucine-auxotrophic version
of the single-ubiquitin yeast strains, P. Sorger and B. Millard for
helpful discussions about the manuscript and technical assistance on
NF-kappa B activation experiments, A. Sliva for assistance with yeast
experiments, B. Schmitt for assistance with binding experiments, A. Hess
for help with statistical analyses and T. Yao for many helpful
discussions. J.J.S. is supported by a fellowship from the Damon Runyon
Cancer Research Foundation (DRG#2073-11). This work was supported, in
part, by US National Institutes of Health (NIH) Common Fund grant
RR020839 (J.D.B.), NIH grant P01 CA139980 (P. Sorger), US National
Institute of Neurologial Disorders and Stroke Intramural Program
(R.J.Y.), and NIH grants RC1 GM091424 (R. E. C.) and 1R01 GM097452
(R.E.C.).
NR 36
TC 45
Z9 45
U1 1
U2 26
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1548-7091
J9 NAT METHODS
JI Nat. Methods
PD MAR
PY 2012
VL 9
IS 3
BP 303
EP U122
DI 10.1038/NMETH.1888
PG 9
WC Biochemical Research Methods
SC Biochemistry & Molecular Biology
GA 900ME
UT WOS:000300890400029
PM 22306808
ER
PT J
AU Lucantonio, F
Stalnaker, TA
Shaham, Y
Niv, Y
Schoenbaum, G
AF Lucantonio, Federica
Stalnaker, Thomas A.
Shaham, Yavin
Niv, Yael
Schoenbaum, Geoffrey
TI The impact of orbitofrontal dysfunction on cocaine addiction
SO NATURE NEUROSCIENCE
LA English
DT Review
ID ORBITAL PREFRONTAL CORTEX; DECISION-MAKING; DRUG-ADDICTION; BASOLATERAL
AMYGDALA; NEURONAL-ACTIVITY; METHAMPHETAMINE ABUSERS; AMPHETAMINE
EXPOSURE; BEHAVIORAL-CONTROL; REWARD PREFERENCE; EXPERIENCED RATS
AB Cocaine addiction is characterized by poor judgment and maladaptive decision-making. Here we review evidence implicating the orbitofrontal cortex in such behavior. This evidence suggests that cocaine-induced changes in orbitofrontal cortex disrupt the representation of states and transition functions that form the basis of flexible and adaptive 'model-based' behavioral control. By impairing this function, cocaine exposure leads to an overemphasis on less flexible, maladaptive 'model-free' control systems. We propose that such an effect accounts for the complex pattern of maladaptive behaviors associated with cocaine addiction.
C1 [Lucantonio, Federica; Schoenbaum, Geoffrey] Univ Maryland, Sch Med, Dept Anat & Neurobiol, Baltimore, MD 21201 USA.
[Stalnaker, Thomas A.; Shaham, Yavin; Schoenbaum, Geoffrey] Natl Inst Drug Abuse, Intramural Res Program, Baltimore, MD USA.
[Niv, Yael] Princeton Univ, Dept Psychol, Princeton, NJ 08544 USA.
[Niv, Yael] Princeton Univ, Inst Neurosci, Princeton, NJ 08544 USA.
RP Schoenbaum, G (reprint author), Univ Maryland, Sch Med, Dept Anat & Neurobiol, Baltimore, MD 21201 USA.
EM schoenbg@schoenbaumlab.org
RI shaham, yavin/G-1306-2014
FU US National Institute on Drug Abuse
FX This review is dedicated to the family of Jacob Peter Waletzky. The work
of writing it was supported by funding from the intramural and
extramural programs of the US National Institute on Drug Abuse,
including time while G. S. and T. A. S. were employed at the University
of Maryland, Baltimore. The opinions expressed in this article are the
author's own and do not reflect the view of the US National Institutes
of Health, the Department of Health and Human Services, or the United
States government.
NR 100
TC 78
Z9 79
U1 2
U2 25
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 MAR
PY 2012
VL 15
IS 3
BP 358
EP 366
DI 10.1038/nn.3014
PG 9
WC Neurosciences
SC Neurosciences & Neurology
GA 899CY
UT WOS:000300793100007
PM 22267164
ER
PT J
AU Schmitz, A
Grillon, C
AF Schmitz, Anja
Grillon, Christian
TI Assessing fear and anxiety in humans using the threat of predictable and
unpredictable aversive events (the NPU-threat test)
SO NATURE PROTOCOLS
LA English
DT Article
ID COMMON MENTAL-DISORDERS; POTENTIATED STARTLE; BED NUCLEUS; ANXIOUS
RESPONSES; UNCERTAIN THREAT; CONTEXTUAL FEAR; CUED FEAR; STIMULI;
STRESS; LESIONS
AB The threat of predictable and unpredictable aversive events was developed to assess short-duration (fear) and long-duration (anxiety) aversive states in humans. A typical experiment consists of three conditions: a safe condition (neutral (N)), during which participants are safe from aversive stimuli, and two threat conditions-one in which aversive events are administered predictably (P) (i.e., signaled by a threat cue), and one in which aversive stimuli are administered unpredictably (U). During the so-called NPU-threat test, ongoing change in aversive states is measured with the startle reflex. The NPU-threat test has been validated in pharmacological and clinical studies and can be implemented in children and adults. Similar procedures have been applied in animal models, making the NPU-threat test an ideal tool for translational research. The procedure is relatively short (35 min), simple to implement and generates consistent results with large effect sizes.
C1 [Schmitz, Anja] NIMH, Genet Epidemiol Res Branch, Bethesda, MD 20892 USA.
[Grillon, Christian] NIMH, Sect Neurobiol Fear & Anxiety, Bethesda, MD 20892 USA.
RP Schmitz, A (reprint author), NIMH, Genet Epidemiol Res Branch, Bethesda, MD 20892 USA.
EM schmitza2@mail.nih.gov
FU NIMH [MH002798, MH002804-09]
FX This research was supported by the Intramural Research Program of the
NIMH (MH002798 and MH002804-09).
NR 36
TC 65
Z9 65
U1 3
U2 32
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1754-2189
J9 NAT PROTOC
JI Nat. Protoc.
PD MAR
PY 2012
VL 7
IS 3
BP 527
EP 532
DI 10.1038/nprot.2012.001
PG 6
WC Biochemical Research Methods
SC Biochemistry & Molecular Biology
GA 901FQ
UT WOS:000300948500010
PM 22362158
ER
PT J
AU Peters, JM
Shah, YM
Gonzalez, FJ
AF Peters, Jeffrey M.
Shah, Yatrik M.
Gonzalez, Frank J.
TI The role of peroxisome proliferator-activated receptors in
carcinogenesis and chemoprevention
SO NATURE REVIEWS CANCER
LA English
DT Review
ID BETA/DELTA PPAR-BETA/DELTA; BREAST-CANCER CELLS; ENDOTHELIAL
GROWTH-FACTOR; RETINOID-X-RECEPTOR; PHASE-II TRIAL; DIFFERENTIATED
THYROID-CANCER; GAMMA AGONIST TROGLITAZONE; HUMAN HACAT KERATINOCYTES;
TRAIL-INDUCED APOPTOSIS; HUMAN PANCREATIC-CANCER
AB Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors that are involved in regulating glucose and lipid homeostasis, inflammation, proliferation and differentiation. Although all of these functions might contribute to the influence of PPARs in carcinogenesis, there is a distinct need for a review of the literature and additional experimentation to determine the potential for targeting PPARs for cancer therapy and cancer chemoprevention. As PPAR agonists include drugs that are used for the treatment of metabolic diseases, a more complete understanding of the roles of PPARs in cancer will aid in determining any increased cancer risk for patients undergoing therapy with PPAR agonists.
C1 [Peters, Jeffrey M.] Penn State Univ, Dept Vet & Biomed Sci, University Pk, PA 16802 USA.
[Peters, Jeffrey M.] Penn State Univ, Ctr Mol Toxicol & Carcinogenesis, University Pk, PA 16802 USA.
[Shah, Yatrik M.] Univ Michigan, Dept Mol & Integrat Physiol, Dept Internal Med, Div Gastroenterol, Ann Arbor, MI 48109 USA.
[Gonzalez, Frank J.] NCI, Lab Metab, Bethesda, MD 20892 USA.
RP Peters, JM (reprint author), Penn State Univ, Dept Vet & Biomed Sci, University Pk, PA 16802 USA.
EM jmp21@psu.edu
FU US National Institutes of Health [CA124533, CA126826, CA141029,
CA140369, AA018863, R01CA148828]; National Cancer Institute
[ZIABC005561, ZIABC005562, ZIABC005708]
FX The authors gratefully acknowledge J. Corell for technical assistance
with the figures and P. Devchand for critical review and suggestions for
the manuscript. The authors' research is supported by the US National
Institutes of Health (CA124533, CA126826, CA141029, CA140369 and
AA018863) to J. M. P., (R01CA148828) to Y.M.S. and the National Cancer
Institute Intramural Research Program (ZIABC005561, ZIABC005562 and
ZIABC005708) to F.J.G.
NR 232
TC 135
Z9 141
U1 0
U2 22
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1474-175X
J9 NAT REV CANCER
JI Nat. Rev. Cancer
PD MAR
PY 2012
VL 12
IS 3
BP 181
EP 195
DI 10.1038/nrc3214
PG 15
WC Oncology
SC Oncology
GA 899RK
UT WOS:000300833600011
PM 22318237
ER
PT J
AU Blagoev, KB
Wilkerson, J
Fojo, T
AF Blagoev, Krastan B.
Wilkerson, Julia
Fojo, Tito
TI Hazard ratios in cancer clinical trials-a primer
SO NATURE REVIEWS CLINICAL ONCOLOGY
LA English
DT Article
ID PANCREATIC NEUROENDOCRINE TUMORS; RENAL-CELL CARCINOMA; SUNITINIB; MODEL
AB The increase and diversity of clinical trial data has resulted in a greater reliance on statistical analyses to discern value. Assessing differences between two similar survival curves can pose a challenge for those without formal training in statistical interpretation; therefore, there has been an increased reliance on hazard ratios often to the exclusion of more-traditional survival measures. However, because a hazard ratio lacks dimensions it can only inform the reader about the reliability and uniformity of the data. It does not provide practitioners with quantitative values they can use, nor does it provide information they can discuss with patients. Motivated by a non-scientific poll of oncologists in training and those with board certification that suggested only a limited understanding of the derivation of hazard ratios we undertook this presentation of hazard ratios: a measure of treatment efficacy that is increasingly used and often misused.
C1 [Wilkerson, Julia; Fojo, Tito] NCI, Med Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA.
[Blagoev, Krastan B.] Natl Sci Fdn, Div Phys, Arlington, VA 22230 USA.
RP Fojo, T (reprint author), NCI, Med Oncol Branch, Ctr Canc Res, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM fojot@mail.nih.gov
OI Wilkerson, Julia/0000-0002-6965-0867
FU National Science Foundation
FX K. B. Blagoev would like to acknowledge that this work was supported in
part by the National Science Foundation. Any opinion, finding,
conclusions or recommendations expressed in this material are those of
the authors and do not necessarily reflect the views of the National
Science Foundation.
NR 18
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 1759-4774
J9 NAT REV CLIN ONCOL
JI Nat. Rev. Clin. Oncol.
PD MAR
PY 2012
VL 9
IS 3
BP 178
EP 183
DI 10.1038/nrclinonc.2011.217
PG 6
WC Oncology
SC Oncology
GA 901DX
UT WOS:000300943000008
PM 22290283
ER
PT J
AU Zumla, A
Hafner, R
Lienhardt, C
Hoelscher, M
Nunn, A
AF Zumla, Alimuddin
Hafner, Richard
Lienhardt, Christian
Hoelscher, Michael
Nunn, Andrew
TI Advancing the development of tuberculosis therapy
SO NATURE REVIEWS DRUG DISCOVERY
LA English
DT Editorial Material
C1 [Zumla, Alimuddin] UCL, Div Infect & Immun, London NW3 2PF, England.
[Hafner, Richard] NIAID, US Natl Inst Hlth, Bethesda, MD 20892 USA.
[Lienhardt, Christian] WHO, Stop TB Partnership, CH-1211 Geneva, Switzerland.
[Hoelscher, Michael] Univ Munich, Div Infect Dis & Trop Med, D-80802 Munich, Germany.
[Nunn, Andrew] MRC, London NW1 2DA, England.
RP Zumla, A (reprint author), UCL, Div Infect & Immun, London NW3 2PF, England.
EM a.zumla@ucl.ac.uk
RI Hoelscher, Michael/D-3436-2012;
OI Zumla, Alimuddin/0000-0002-5111-5735
FU Medical Research Council [MC_U122888469]
NR 5
TC 34
Z9 35
U1 0
U2 13
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1474-1776
J9 NAT REV DRUG DISCOV
JI Nat. Rev. Drug Discov.
PD MAR
PY 2012
VL 11
IS 3
BP 170
EP 171
DI 10.1038/nrd3694
PG 2
WC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy
SC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy
GA 901CV
UT WOS:000300940200001
PM 22378254
ER
PT J
AU Kelloff, GJ
Sigman, CC
AF Kelloff, Gary J.
Sigman, Caroline C.
TI Cancer biomarkers: selecting the right drug for the right patient
SO NATURE REVIEWS DRUG DISCOVERY
LA English
DT Article
ID CELL LUNG-CANCER; POSITRON-EMISSION-TOMOGRAPHY; CLINICAL-TRIAL DESIGN;
SURROGATE END-POINTS; ADAPTIVE SIGNATURE DESIGN; CIRCULATING
TUMOR-CELLS; BREAST-CANCER; INTRAEPITHELIAL NEOPLASIA;
MONOCLONAL-ANTIBODY; GENETIC ALTERATIONS
AB This Perspective highlights biomarkers that are expressed as a consequence of cancer development and progression. We focus on those biomarkers that are most relevant for identifying patients who are likely to respond to a given therapy, as well as those biomarkers that are most effective for measuring patient response to therapy. These two measures are necessary for selecting the right drug for the right patient, regardless of whether the setting is in drug development or in the post-approval use of the drug for patients with cancer. We also discuss the innovative designs of clinical trials and methodologies that are used to validate and qualify biomarkers for use in specific contexts. Furthermore, we look ahead to the promises and challenges in the field of cancer biomarkers.
C1 [Kelloff, Gary J.] NCI, Canc Imaging Program, Bethesda, MD 20852 USA.
[Sigman, Caroline C.] CCS Associates, Mountain View, CA 94043 USA.
RP Kelloff, GJ (reprint author), NCI, Canc Imaging Program, EPN Rm 6058,6130 Execut Blvd, Bethesda, MD 20852 USA.
EM kelloffg@mail.nih.gov; csigman@ccsainc.com
NR 117
TC 105
Z9 110
U1 3
U2 23
PU NATURE PUBLISHING GROUP
PI LONDON
PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND
SN 1474-1776
EI 1474-1784
J9 NAT REV DRUG DISCOV
JI Nat. Rev. Drug Discov.
PD MAR
PY 2012
VL 11
IS 3
BP 201
EP 214
DI 10.1038/nrd3651
PG 14
WC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy
SC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy
GA 901CV
UT WOS:000300940200022
PM 22322254
ER
PT J
AU Balow, JE
AF Balow, James E.
TI Perspectives on maintenance therapy in lupus nephritis
SO NATURE REVIEWS NEPHROLOGY
LA English
DT News Item
ID MYCOPHENOLATE-MOFETIL; CONTROLLED-TRIAL; CYCLOPHOSPHAMIDE; AZATHIOPRINE;
PREDNISONE
AB Maintenance immunosuppressive drug therapy is necessary to counter the propensity of lupus nephritis to relapse. Claims that mycophenolate mofetil might be the magic bullet for both induction and maintenance therapies merit critical reappraisal due to inconsistent evidence of the superiority of mycophenolate mofetil over azathioprine, as well as its inordinately greater cost.
C1 Natl Inst Diabet & Digest & Kidney Dis, Kidney Dis Sect, NIH, Clin Res Ctr, Bethesda, MD 20892 USA.
RP Balow, JE (reprint author), Natl Inst Diabet & Digest & Kidney Dis, Kidney Dis Sect, NIH, Clin Res Ctr, Room 5-2551, Bethesda, MD 20892 USA.
EM james.e.balow@nih.gov
FU Intramural NIH HHS [Z99 DK999999, ZIA DK043414-07]
NR 10
TC 2
Z9 2
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 1759-5061
J9 NAT REV NEPHROL
JI Nat. Rev. Nephrol.
PD MAR
PY 2012
VL 8
IS 3
BP 136
EP 138
DI 10.1038/nrneph.2012.17
PG 4
WC Urology & Nephrology
SC Urology & Nephrology
GA 900KW
UT WOS:000300886900003
PM 22310950
ER
PT J
AU Spencer, R
AF Spencer, Richard
TI Magnetic resonance in tissue engineering
SO NMR IN BIOMEDICINE
LA English
DT Editorial Material
C1 NIA, NIH, Intramural Res Program, Baltimore, MD 21224 USA.
RP Spencer, R (reprint author), NIA, NIH, Intramural Res Program, GRC 4D-08,5600 Nathan Shock Dr, Baltimore, MD 21224 USA.
EM spencer@helix.nih.gov
FU Intramural NIH HHS [ZIA AG000923-05]
NR 0
TC 1
Z9 1
U1 0
U2 1
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0952-3480
J9 NMR BIOMED
JI NMR Biomed.
PD MAR
PY 2012
VL 25
IS 3
SI SI
BP 401
EP 401
DI 10.1002/nbm.1806
PG 1
WC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy
SC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy
GA 897QX
UT WOS:000300670600002
PM 22134896
ER
PT J
AU Reiter, DA
Irrechukwu, O
Lin, PC
Moghadam, S
Von Thaer, S
Pleshko, N
Spencer, RG
AF Reiter, David A.
Irrechukwu, Onyi
Lin, Ping-Chang
Moghadam, Somaieh
Von Thaer, Sarah
Pleshko, Nancy
Spencer, Richard G.
TI Improved MR-based characterization of engineered cartilage using
multiexponential T-2 relaxation and multivariate analysis
SO NMR IN BIOMEDICINE
LA English
DT Article
DE cartilage MRI; multiexponential T-2; support vector machine;
proteoglycan; tissue engineering
ID MAGNETIC-RESONANCE MICROSCOPY; SUPPORT VECTOR MACHINES;
ARTICULAR-CARTILAGE; BIOMECHANICAL PROPERTIES; TISSUE CLASSIFICATION;
COLLAGEN DYNAMICS; SOLID-STATE; MODEL; BRAIN; BONE
AB Noninvasive monitoring of tissue quality would be of substantial use in the development of cartilage tissue engineering strategies. Conventional MR parameters provide noninvasive measures of biophysical tissue properties and are sensitive to changes in matrix development, but do not clearly distinguish between groups with different levels of matrix development. Furthermore, MR outcomes are nonspecific, with particular changes in matrix components resulting in changes in multiple MR parameters. To address these limitations, we present two new approaches for the evaluation of tissue engineered constructs using MR, and apply them to immature and mature engineered cartilage after 1 and 5 weeks of development, respectively. First, we applied multiexponential T-2 analysis for the quantification of matrix macromolecule-associated water compartments. Second, we applied multivariate support vector machine analysis using multiple MR parameters to improve detection of degree of matrix development. Monoexponential T-2 values decreased with maturation, but without further specificity. Much more specific information was provided by multiexponential analysis. The T-2 distribution in both immature and mature constructs was qualitatively comparable to that of native cartilage. The analysis showed that proteoglycan-bound water increased significantly during maturation, from a fraction of 0.05 +/- 0.01 to 0.07 +/- 0.01. Classification of samples based on individual MR parameters, T-1, T-2, km or apparent diffusion coefficient, showed that the best classifiers were T-1 and km, with classification accuracies of 85% and 84%, respectively. Support vector machine analysis improved the accuracy to 98% using the combination (km, apparent diffusion coefficient). These approaches were validated using biochemical and Fourier transform infrared imaging spectroscopic analyses, which showed increased proteoglycan and collagen with maturation. In summary, multiexponential T2 and multivariate support vector machine analyses provide improved sensitivity to changes in matrix development and specificity to matrix composition in tissue engineered cartilage. These approaches show substantial potential for the evaluation of engineered cartilage tissue and for extension to other tissue engineering constructs. Copyright (c) 2012 John Wiley & Sons, Ltd.
C1 [Reiter, David A.] NIA, Clin Res Branch, NIH, Baltimore, MD 21225 USA.
[Irrechukwu, Onyi; Lin, Ping-Chang; Von Thaer, Sarah; Spencer, Richard G.] NIA, Magnet Resonance Imaging & Spect Sect, NIH, Baltimore, MD 21225 USA.
[Moghadam, Somaieh; Pleshko, Nancy] Temple Univ, Dept Mech Engn, Philadelphia, PA 19122 USA.
RP Reiter, DA (reprint author), NIA, Clin Res Branch, NIH, 3001 S Hanover St,5th Floor, Baltimore, MD 21225 USA.
EM reiterda@mail.nih.gov
OI Lin, Ping-Chang/0000-0003-0918-4072
FU National Institutes of Health (NIH); National Institute on Aging; NIH
[R01 EB000744, NIH AR056145]
FX This work was supported in part by the Intramural Research Program of
the National Institutes of Health (NIH), National Institute on Aging,
and by NIH R01 EB000744 (NP) and NIH AR056145 (NP).
NR 63
TC 15
Z9 17
U1 1
U2 9
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0952-3480
J9 NMR BIOMED
JI NMR Biomed.
PD MAR
PY 2012
VL 25
IS 3
SI SI
BP 476
EP 488
DI 10.1002/nbm.1804
PG 13
WC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy
SC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy
GA 897QX
UT WOS:000300670600010
PM 22287335
ER
PT J
AU Inamoto, Y
Chai, XY
Kurland, BF
Cutler, C
Flowers, MED
Palmer, JM
Carpenter, PA
Heffernan, MJ
Jacobsohn, D
Jagasia, MH
Pidala, J
Khera, N
Vogelsang, GB
Weisdorf, D
Martin, PJ
Pavletic, SZ
Lee, SJ
AF Inamoto, Yoshihiro
Chai, Xiaoyu
Kurland, Brenda F.
Cutler, Corey
Flowers, Mary E. D.
Palmer, Jeanne M.
Carpenter, Paul A.
Heffernan, Mary J.
Jacobsohn, David
Jagasia, Madan H.
Pidala, Joseph
Khera, Nandita
Vogelsang, Georgia B.
Weisdorf, Daniel
Martin, Paul J.
Pavletic, Steven Z.
Lee, Stephanie J.
CA Chronic GVHD Consortium
TI Validation of Measurement Scales in Ocular Graft-versus-Host Disease
SO OPHTHALMOLOGY
LA English
DT Article; Proceedings Paper
CT BMT Tandem Meeting
CY FEB, 2011
CL Honolulu, HI
ID QUALITY-OF-LIFE; CONSENSUS DEVELOPMENT PROJECT;
BONE-MARROW-TRANSPLANTATION; WORKING GROUP-REPORT; STEM-CELL
TRANSPLANTATION; DRY EYE SYNDROME; TERM-FOLLOW-UP; CLINICAL-TRIALS;
THERAPEUTIC RESPONSE; HEALTH-STATUS
AB Purpose: To validate measurement scales for rating ocular chronic graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation. Candidate scales were recommended for use in clinical trials by the National Institutes of Health (NIH) Chronic GVHD Consensus Conference or have been previously validated in dry eye syndromes.
Design: Prospective follow-up study.
Participants: Between August 2007 and June 2010, the study enrolled 387 patients with chronic GVHD in a multicenter, prospective, observational cohort.
Methods: Using anchor-based methods, we compared clinician or patient-reported changes in eye symptoms (8-point scale) with calculated changes in 5 candidate scales: The NIH eye score, patient-reported global rating of eye symptoms, Lee eye subscale, Ocular Surface Disease Index, and Schirmer test. Change was examined for 333 follow-up visits where both clinician and patient reported eye involvement at the previous visit. Linear mixed models were used to account for within-patient correlation.
Main Outcome Measures: An 8-point scale of clinician or patient-reported symptom change was used as an anchor to measure symptom changes at the follow-up visits.
Results: In serial evaluations, agreement regarding improvement, stability, or worsening between the clinician and patient was fair (weighted kappa = 0.34). Despite only fair agreement between evaluators, all scales except the Schirmer test correlated with both clinician-reported and patient-reported changes in ocular GVHD activity. Among all scales, changes in the NIH eye scores showed the greatest sensitivity to symptom change reported by clinicians or patients.
Conclusions: Our results support the use of the NIH eye score as a sensitive measure of eye symptom changes in clinical trials assessing treatment of chronic GVHD.
Financial Disclosure(s): The authors have no proprietary or commercial interest in any materials discussed in this article. Ophthalmology 2012;119:487-493 (C) 2012 by the American Academy of Ophthalmology.
C1 [Inamoto, Yoshihiro; Chai, Xiaoyu; Kurland, Brenda F.; Flowers, Mary E. D.; Carpenter, Paul A.; Heffernan, Mary J.; Khera, Nandita; Martin, Paul J.; Lee, Stephanie J.] Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98109 USA.
[Cutler, Corey] Dana Farber Canc Inst, Boston, MA 02115 USA.
[Palmer, Jeanne M.] Med Coll Wisconsin, Div Hematol Oncol, Milwaukee, WI 53226 USA.
[Jacobsohn, David] Childrens Natl Med Ctr, Ctr Canc & Blood Disorders, Div Blood & Marrow Transplantat, Washington, DC 20010 USA.
[Jagasia, Madan H.] Vanderbilt Univ, Med Ctr, Hematol & Stem Cell Transplant Program, Nashville, TN USA.
[Pidala, Joseph] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA.
[Vogelsang, Georgia B.] Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA.
[Weisdorf, Daniel] Univ Minnesota, Blood & Marrow Transplant Program, Minneapolis, MN USA.
[Pavletic, Steven Z.] NCI, Bethesda, MD 20892 USA.
RP Lee, SJ (reprint author), Fred Hutchinson Canc Res Ctr, Div Clin Res, 1100 Fairview Ave N,D5-290, Seattle, WA 98109 USA.
EM sjlee@fhcrc.org
OI Kurland, Brenda/0000-0002-5669-0595
FU NCI NIH HHS [U01 CA118953, CA118953, CA18029, P01 CA018029, P30
CA015704, R01 CA118953, U01 CA118953-05, U54 CA163438]
NR 37
TC 30
Z9 30
U1 2
U2 5
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0161-6420
J9 OPHTHALMOLOGY
JI Ophthalmology
PD MAR
PY 2012
VL 119
IS 3
BP 487
EP 493
DI 10.1016/j.ophtha.2011.08.040
PG 7
WC Ophthalmology
SC Ophthalmology
GA 901ID
UT WOS:000300957200009
PM 22153706
ER
PT J
AU Momynaliev, KT
Gorbatenko, EV
Shevtsov, AB
Gribanov, OG
Babenko, NN
Kaabak, MM
AF Momynaliev, K. T.
Gorbatenko, E. V.
Shevtsov, A. B.
Gribanov, O. G.
Babenko, N. N.
Kaabak, M. M.
TI Prevalence and subtypes of BK virus in pediatric renal transplant
recipients in Russia
SO PEDIATRIC TRANSPLANTATION
LA English
DT Article
DE transplantation; kidney; BK virus; qualitative PCR
ID POLYOMAVIRUS-ASSOCIATED NEPHROPATHY; SEQUENCE ALIGNMENT;
HUMAN-POPULATIONS; DNA-SEQUENCES; JC VIRUS; MARKER; CYCLOSPORINE;
PERSISTENCE; INFECTION; IMPACT
AB BKV reactivation is associated with impaired graft function in kidney transplant patients. The objective of our study was to determine the prevalence of BKV infection in consecutive pediatric kidney transplant recipients at our center. Fifty-eight pediatric kidney transplant recipients were studied. The mean age at screening was 9.4 +/- 2.8 yr, and samples were obtained at a median of 2.4 +/- 1.4 yr after transplantation. BKV-DNA was analyzed in urine and plasma by quantitative PCR. Occurrences of BK-DNAuria and BK-DNAemia did not change in the first two yr after transplantation in children and amounted to 21-23% and 7-8%, respectively (p > 0.05). In the third year, the occurrences of BK-DNAuria and BK-DNAemia increased insignificantly to 27% and 9% in the pediatric patients. We also determined the subtypes and subgroups of BK virus isolated from Russian renal transplant recipients and found that BKV isolates were composed of subtypes Ib-2 and IV/c2. The data we obtained indicate that although only 5% of BKVAN cases occurred between years two and five post-transplantation, it seems necessary to regularly monitor pediatric patients for BKV infection through the third year after transplantation.
C1 [Momynaliev, K. T.; Gribanov, O. G.] Fed Agcy Biol & Med, Res Inst Physicochem Med, Moscow 119992, Russia.
[Momynaliev, K. T.; Shevtsov, A. B.] Natl Biotechnol Ctr, Astana, Kazakhstan.
[Gorbatenko, E. V.] Lytech Ltd, Moscow, Russia.
[Babenko, N. N.; Kaabak, M. M.] Russian Acad Med Sci, Russian Natl Res Ctr Surg, Moscow, Russia.
RP Momynaliev, KT (reprint author), Fed Agcy Biol & Med, Res Inst Physicochem Med, 1A Malaya Pirogovskaya St, Moscow 119992, Russia.
EM dhoroshun@gmail.com
OI Shevtsov, Alexandr/0000-0002-7576-2750; Kaabak,
Michael/0000-0001-7566-2330; Babenko, Nadezda/0000-0002-4651-4061
NR 33
TC 1
Z9 1
U1 1
U2 1
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1397-3142
J9 PEDIATR TRANSPLANT
JI Pediatr. Transplant.
PD MAR
PY 2012
VL 16
IS 2
BP 151
EP 159
DI 10.1111/j.1399-3046.2011.01640.x
PG 9
WC Pediatrics; Transplantation
SC Pediatrics; Transplantation
GA 898BF
UT WOS:000300709600014
PM 22300090
ER
PT J
AU Vollrath-Smith, FR
Shin, R
Ikemoto, S
AF Vollrath-Smith, Fiori R.
Shin, Rick
Ikemoto, Satoshi
TI Synergistic interaction between baclofen administration into the median
raphe nucleus and inconsequential visual stimuli on investigatory
behavior of rats
SO PSYCHOPHARMACOLOGY
LA English
DT Article
DE Median and dorsal raphe nuclei; GABA(B) receptors; Baclofen; Serotonin;
Dopamine; Visual stimuli; Incentive motivation; Sensation seeking
ID GABA-B RECEPTORS; D-AMPHETAMINE; CONDITIONED REWARD; STRIATAL
SUBREGIONS; SEROTONIN NEURONS; DOPAMINE; REINFORCEMENT; ACCUMBENS;
NICOTINE; MICROINJECTIONS
AB Rationale Noncontingent administration of amphetamine into the ventral striatum or systemic nicotine increases responses rewarded by inconsequential visual stimuli. When these drugs are contingently administered, rats learn to self-administer them. We recently found that rats self-administer the GABA(B) receptor agonist baclofen into the median (MR) or dorsal (DR) raphe nuclei.
Objectives We examined whether noncontingent administration of baclofen into the MR or DR increases rats' investigatory behavior rewarded by a flash of light.
Results Contingent presentations of a flash of light slightly increased lever presses. Whereas noncontingent administration of baclofen into the MR or DR did not reliably increase lever presses in the absence of visual stimulus reward, the same manipulation markedly increased lever presses rewarded by the visual stimulus. Heightened locomotor activity induced by intraperitoneal injections of amphetamine (3 mg/kg) failed to concur with increased lever pressing for the visual stimulus. These results indicate that the observed enhancement of visual stimulus seeking is distinct from an enhancement of general locomotor activity. Visual stimulus seeking decreased when baclofen was co-administered with the GABA(B) receptor antagonist, SCH 50911, confirming the involvement of local GABA(B) receptors. Seeking for visual stimulus also abated when baclofen administration was preceded by intraperitoneal injections of the dopamine antagonist, SCH 23390 (0.025 mg/kg), suggesting enhanced visual stimulus seeking depends on intact dopamine signals.
Conclusions Baclofen administration into the MR or DR increased investigatory behavior induced by visual stimuli. Stimulation of GABA(B) receptors in the MR and DR appears to disinhibit the motivational process involving stimulus-approach responses.
C1 [Vollrath-Smith, Fiori R.; Shin, Rick; Ikemoto, Satoshi] NIDA, Behav Neurosci Branch, NIH, US Dept HHS, Baltimore, MD 21224 USA.
RP Ikemoto, S (reprint author), NIDA, Behav Neurosci Branch, NIH, US Dept HHS, 251 Bayview Blvd,Suite 200, Baltimore, MD 21224 USA.
EM sikemoto@intra.nida.nih.gov
OI Ikemoto, Satoshi/0000-0002-0732-7386
FU National Institute on Drug Abuse, National Institutes of Health
FX This work was supported by the Intramural Research Program of the
National Institute on Drug Abuse, National Institutes of Health. The
authors thank the NIH Fellows Editorial Board for editorial assistance.
We declare that we do not have any financial conflict of interest and
that the experiments comply with the current laws of the USA in which
they were performed.
NR 39
TC 4
Z9 4
U1 0
U2 1
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0033-3158
J9 PSYCHOPHARMACOLOGY
JI Psychopharmacology
PD MAR
PY 2012
VL 220
IS 1
BP 15
EP 25
DI 10.1007/s00213-011-2450-x
PG 11
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 898ZH
UT WOS:000300780400002
PM 21904820
ER
PT J
AU Robinson, JE
Fish, EW
Krouse, MC
Thorsell, A
Heilig, M
Malanga, CJ
AF Robinson, J. E.
Fish, E. W.
Krouse, M. C.
Thorsell, A.
Heilig, M.
Malanga, C. J.
TI Potentiation of brain stimulation reward by morphine: effects of
neurokinin-1 receptor antagonism
SO PSYCHOPHARMACOLOGY
LA English
DT Article
DE Morphine; Opioid; Neurokinin; Substance P; Dopamine; Reward;
Reinforcement
ID INTRACRANIAL SELF-STIMULATION; VENTRAL TEGMENTAL AREA; CONDITIONED PLACE
PREFERENCE; MEDIAL FOREBRAIN-BUNDLE; MU-OPIOID RECEPTORS; SUBSTANCE-P;
NUCLEUS-ACCUMBENS; DOPAMINE RELEASE; NK1 RECEPTOR; MICE LACKING
AB Rationale The abuse potential of opioids may be due to their reinforcing and rewarding effects, which may be attenuated by neurokinin-1 receptor (NK1R) antagonists.
Objective This study was conducted to measure the effects of opioid and NK1R blockade on the potentiation of brain stimulation reward (BSR) by morphine using the intracranial self-stimulation method.
Methods Adult male C57BL/6J mice (n=15) were implanted with unipolar stimulating electrodes in the lateral hypothalamus and trained to respond for varying frequencies of rewarding electrical stimulation. The BSR threshold (theta(0)) and maximum response rate (MAX) were determined before and after intraperitoneal administration of saline, morphine (1.0-17.0 mg/kg), or the NK1R antagonists L-733,060 (1.0-17.0 mg/kg) and L-703,606 (1.0-17.0 mg/kg). In morphine antagonism experiments, naltrexone (0.1-1.0 mg/kg) or 10.0 mg/kg L-733,060 or L-703,606 was administered 15 min before morphine (1.0-10.0 mg/kg) or saline.
Results Morphine dose-dependently decreased theta(0) (maximum effect=62% of baseline) and altered MAX when compared to saline. L-703,606 and L-733,060 altered theta(0); 10.0 mg/kg L-733,060 and L-703,606, which did not affect theta(0) or MAX, attenuated the effects of 3.0 and 10.0 mg/kg morphine, and 1.0 and 0.3 mg/kg naltrexone blocked the effects of 10.0 mg/kg morphine. Naltrexone given before saline did not affect theta(0) or MAX.
Conclusions The decrease in theta(0) by morphine reflects its rewarding effects, which were attenuated by NK1R and opioid receptor blockade. These results demonstrate the importance of substance P signaling during limbic reward system activation by opioids.
C1 [Robinson, J. E.; Fish, E. W.; Krouse, M. C.; Malanga, C. J.] Univ N Carolina, Dept Neurol, Chapel Hill, NC 27599 USA.
[Robinson, J. E.; Fish, E. W.; Krouse, M. C.; Malanga, C. J.] Univ N Carolina, Bowles Ctr Alcohol Studies, Chapel Hill, NC 27599 USA.
[Thorsell, A.; Heilig, M.] NIAAA, Lab Clin & Translat Studies, NIH, Bethesda, MD USA.
RP Malanga, CJ (reprint author), Univ N Carolina, Dept Neurol, 170 Manning Dr,CB 7025, Chapel Hill, NC 27599 USA.
EM malangacj@neurology.unc.edu
OI Malanga, C.J./0000-0003-4808-3995; Robinson, J.
Elliott/0000-0001-9417-3938; Thorsell, Annika/0000-0003-3535-3845
FU NIAAA; [R01-AA 018335]
FX This research was supported by R01-AA 018335 (CJM) and the NIAAA
intramural research budget (MH).
NR 91
TC 16
Z9 16
U1 0
U2 0
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0033-3158
EI 1432-2072
J9 PSYCHOPHARMACOLOGY
JI Psychopharmacology
PD MAR
PY 2012
VL 220
IS 1
BP 215
EP 224
DI 10.1007/s00213-011-2469-z
PG 10
WC Neurosciences; Pharmacology & Pharmacy; Psychiatry
SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry
GA 898ZH
UT WOS:000300780400020
PM 21909635
ER
PT J
AU Cappellacci, L
Petrelli, R
Vita, P
Torquati, I
Jacobson, KA
Barrett, MO
Franklin, D
Harden, KT
Franchetti, P
Grifantini, M
AF Cappellacci, Loredana
Petrelli, Riccardo
Vita, Patrizia
Torquati, Ilaria
Jacobson, Kenneth A.
Barrett, Matthew O.
Franklin, Derek
Harden, Kendall T.
Franchetti, Palmarisa
Grifantini, Mario
TI ADP- and ATP-mimetics derived from 2 '(3 ')-C-methyladenosine as human
P2Y(1) and P2Y(2) receptor ligands
SO PURINERGIC SIGNALLING
LA English
DT Meeting Abstract
C1 [Cappellacci, Loredana; Petrelli, Riccardo; Vita, Patrizia; Torquati, Ilaria; Franchetti, Palmarisa; Grifantini, Mario] Univ Camerino, Med Chem Unit, Sch Pharm, I-62032 Camerino, MC, Italy.
[Jacobson, Kenneth A.] NIDDK, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
[Barrett, Matthew O.; Franklin, Derek; Harden, Kendall T.] Univ N Carolina, Sch Med, Dept Pharmacol, Chapel Hill, NC 27599 USA.
RI Jacobson, Kenneth/A-1530-2009
OI Jacobson, Kenneth/0000-0001-8104-1493
NR 2
TC 1
Z9 1
U1 0
U2 3
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 1573-9538
J9 PURINERG SIGNAL
JI Purinergic Signal.
PD MAR
PY 2012
VL 8
IS 1
BP 143
EP 143
PG 1
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 898YO
UT WOS:000300778500068
ER
PT J
AU Bonaventura, J
Brugarolas, M
Navarro, G
Mallol, J
Canela, EI
Lluis, C
Franco, R
Meana, J
Salles, J
Cortes, A
Casado, V
Ferre, S
AF Bonaventura, Jordi
Brugarolas, Marc
Navarro, Gemma
Mallol, Josefa
Canela, Enric I.
Lluis, Carme
Franco, Rafael
Meana, Javier
Salles, Joan
Cortes, Antoni
Casado, Vicent
Ferre, Sergi
TI Caffeine and other A(2A) ligands modulate the binding of raclopride to
D2 receptors
SO PURINERGIC SIGNALLING
LA English
DT Meeting Abstract
C1 [Bonaventura, Jordi; Brugarolas, Marc; Navarro, Gemma; Mallol, Josefa; Canela, Enric I.; Lluis, Carme; Franco, Rafael; Cortes, Antoni; Casado, Vicent] Univ Barcelona, Fac Biol, Ctr Invest Biomed Red Enfermedades Neurodegenerat, E-08028 Barcelona, Spain.
[Bonaventura, Jordi; Brugarolas, Marc; Navarro, Gemma; Mallol, Josefa; Canela, Enric I.; Lluis, Carme; Franco, Rafael; Cortes, Antoni; Casado, Vicent] Univ Barcelona, Fac Biol, Dept Biochem & Mol Biol, E-08028 Barcelona, Spain.
[Franco, Rafael] Univ Navarra, CIMA, Pamplona 31008, Spain.
[Meana, Javier] Univ Basque Country, Dept Pharmacol, Leioa, Bizkaia, Spain.
[Meana, Javier; Salles, Joan] CIBERSAM, Ctr Invest Biomed Red Salud Mental, Madrid, Spain.
[Salles, Joan] Univ Basque Country, Fac Farm, Dept Pharmacol, Vitoria, Spain.
[Ferre, Sergi] NIDA, Intramural Res Program, NIH, Dept Hlth & Human Serv, Baltimore, MD 21224 USA.
RI Franco, Rafael/C-3694-2015; Salles, Joan/A-7141-2015
OI Franco, Rafael/0000-0003-2549-4919; Salles, Joan/0000-0001-6727-2674
NR 0
TC 0
Z9 0
U1 0
U2 1
PU SPRINGER
PI DORDRECHT
PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS
SN 1573-9538
J9 PURINERG SIGNAL
JI Purinergic Signal.
PD MAR
PY 2012
VL 8
IS 1
BP 172
EP 172
PG 1
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 898YO
UT WOS:000300778500127
ER
PT J
AU Stoddard, J
Takarae, Y
Simon, TJ
AF Stoddard, Joel
Takarae, Yukari
Simon, Tony J.
TI A second look: No effect of the COMT Val158Met polymorphism on conflict
adaptation in youth with chromosome 22q11.2 deletion syndrome
SO SCHIZOPHRENIA RESEARCH
LA English
DT Letter
ID SCHIZOPHRENIA; ADULTS; GENOTYPE; CHILDREN
C1 [Stoddard, Joel; Simon, Tony J.] Univ Calif Davis Hlth Syst, Med Investigat Neurodev Disorders MIND Inst, Dept Psychiat & Behav Sci, Davis, CA USA.
[Stoddard, Joel] NIMH, Mood & Anxiety Disorders Branch, Bethesda, MD USA.
[Takarae, Yukari] Univ Calif Davis, Ctr Mind & Brain, Davis, CA 95616 USA.
RP Stoddard, J (reprint author), Bldg 10,B1D43B2, Bethesda, MD 20892 USA.
EM joel.stoddard@nih.gov
OI Stoddard, Joel/0000-0003-4070-4566
FU NICHD NIH HHS [R01 HD042974]
NR 10
TC 1
Z9 1
U1 0
U2 0
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0920-9964
J9 SCHIZOPHR RES
JI Schizophr. Res.
PD MAR
PY 2012
VL 135
IS 1-3
BP 202
EP 203
DI 10.1016/j.schres.2011.12.011
PG 2
WC Psychiatry
SC Psychiatry
GA 901CT
UT WOS:000300940000039
PM 22245443
ER
PT J
AU Arnaoutova, I
George, J
Kleinman, HK
Benton, G
AF Arnaoutova, Irina
George, Jay
Kleinman, Hynda K.
Benton, Gabriel
TI Basement Membrane Matrix (BME) has Multiple Uses with Stem Cells
SO STEM CELL REVIEWS AND REPORTS
LA English
DT Article
DE Matrigel; Basement membrane; Stem cells; Differentiation; Culture;
Proliferation; BME
ID ENDOTHELIAL PROGENITOR CELLS; EXTRACELLULAR-MATRIX; DIFFERENTIATION;
CULTURE; GROWTH; IDENTIFICATION; TISSUE; LINE; EFFICIENCY; PROTEINS
AB The utilization of basement membrane matrix has helped to overcome many of the obstacles associated with stem cell research. Initially, there were several problems with investigating stem cells, including difficult extraction from tissues, the need for feeder layers, poor survival, minimal proliferation, limited differentiation in vitro, and inadequate survival when injected or transplanted in vivo. Given that the basement membrane is the first extracellular matrix that is produced by the developing embryo, it was quickly identified as an important factor for modulating stem cell behavior, and since then, basement membrane extract (BME) has been successfully employed in numerous methods as a substratum in vitro and as a bioactive support in vivo to overcome many of these problems. A thin BME coating is sufficient to maintain an undifferentiated phenotype during embryonic stem cell expansion, while a thick BME hydrogel may be employed to induce stem cell differentiation. BME also promotes stem cell survival for in vivo applications and provides a physiological environment for evaluating stem cell co-culture with other cell types. The present article provides a concise review of current methodologies utilizing BME for stem cell research.
C1 [Arnaoutova, Irina; George, Jay; Benton, Gabriel] Trevigen Inc, Gaithersburg, MD 20877 USA.
[Kleinman, Hynda K.] NIDCR, NIH, Bethesda, MD USA.
RP Benton, G (reprint author), Trevigen Inc, 8405 Helgerman Ct, Gaithersburg, MD 20877 USA.
EM gbenton@trevigen.com
OI Benton, Gabriel/0000-0003-4244-5764
NR 53
TC 8
Z9 9
U1 2
U2 5
PU HUMANA PRESS INC
PI TOTOWA
PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA
SN 1550-8943
J9 STEM CELL REV REP
JI Stem Cell Rev. Rep.
PD MAR
PY 2012
VL 8
IS 1
BP 163
EP 169
DI 10.1007/s12015-011-9278-y
PG 7
WC Cell & Tissue Engineering; Cell Biology; Medicine, Research &
Experimental
SC Cell Biology; Research & Experimental Medicine
GA 898YT
UT WOS:000300779000015
PM 21655946
ER
PT J
AU Hernandez, DA
Bokkers, RPH
Mirasol, RV
Luby, M
Henning, EC
Merino, JG
Warach, S
Latour, LL
AF Hernandez, Daymara A.
Bokkers, Reinoud P. H.
Mirasol, Raymond V.
Luby, Marie
Henning, Erica C.
Merino, Jose G.
Warach, Steven
Latour, Lawrence L.
TI Pseudocontinuous Arterial Spin Labeling Quantifies Relative Cerebral
Blood Flow in Acute Stroke
SO STROKE
LA English
DT Article
DE acute stroke; cerebral blood flow; perfusion quantification
ID ACUTE ISCHEMIC-STROKE; REPERFUSION; INVERSION; THERAPY; DISEASE; TIME;
MRI
AB Background and Purpose-The aim of this study was to test whether arterial spin labeling (ASL) can detect significant differences in relative cerebral blood flow (rCBF) in the core, mismatch, and reverse-mismatch regions, and whether rCBF values measured by ASL in those areas differ from values obtained using dynamic susceptibility contrast (DSC) MRI.
Methods-Acute stroke patients were imaged with diffusion-weighted imaging (DWI) and perfusion-weighted imaging (ASL and DSC) MRI. An expert reader segmented the ischemic lesion on DWI and the DSC time-to-peak (TTP) maps. Three regions were defined: core (DWI+, TTP+), mismatch (DWI+, TTP+), and reverse-mismatch (DWI+, TTP+). For both ASL and DSC, rCBF maps were created with commercially available software, and the ratio was calculated as the mean signal intensity measured on the side of the lesion to that of the homologous region in the contralateral hemisphere. Values obtained from core, mismatch, and reverse-mismatch were used for paired comparison.
Results-Twenty-eight patients were included in the study. The mean age was 65.6 (16.9) years, with a median baseline National Institutes of Health Stroke Scale score of 10 (interquartile range, 4-17). Median time from last known normal to MRI was 5.7 hours (interquartile range, 2.9-22.6). Mean rCBF ratios were significantly higher in the mismatch 0.53 (0.23) versus the core 0.39 (0.33) and reverse-mismatch 0.68 (0.49) versus the core 0.38 (0.35). Differences in rCBF measured with DSC and ASL were not significant.
Conclusions-ASL allows for the measurement of rCBF in the core and mismatch regions. Values in the mismatch were significantly higher than in the core, suggesting there is potential salvageable tissue. (Stroke. 2012;43:753-758.)
C1 [Hernandez, Daymara A.; Mirasol, Raymond V.; Luby, Marie; Henning, Erica C.; Merino, Jose G.; Warach, Steven; Latour, Lawrence L.] NINDS, NIH, Sect Stroke Diagnost & Therapeut, Bethesda, MD 20892 USA.
[Bokkers, Reinoud P. H.] Univ Med Ctr Utrecht, Dept Radiol, Utrecht, Netherlands.
[Merino, Jose G.] Johns Hopkins Community Phys, Bethesda, MD USA.
[Mirasol, Raymond V.] NIH, Howard Hughes Med Inst, Res Scholars Program, Bethesda, MD 20892 USA.
RP Latour, LL (reprint author), NINDS, NIH, Sect Stroke Diagnost & Therapeut, 10 Ctr Dr,MSC 1063,Bldg 10,Room B1D733, Bethesda, MD 20892 USA.
EM latourl@ninds.nih.gov
OI Merino, Jose/0000-0002-6676-0008
FU Washington Hospital Center Stroke Center; Division of Intramural
Research of the National Institute of Neurological Disorders and Stroke;
National Institutes of Health
FX The authors thank the National Institutes of Health Stroke Program at
the Washington Hospital Center Stroke Center for their support of the
study.; This research was supported by the Division of Intramural
Research of the National Institute of Neurological Disorders and Stroke,
National Institutes of Health.
NR 28
TC 19
Z9 21
U1 0
U2 6
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA
SN 0039-2499
EI 1524-4628
J9 STROKE
JI Stroke
PD MAR
PY 2012
VL 43
IS 3
BP 753
EP 758
DI 10.1161/STROKEAHA.111.635979
PG 6
WC Clinical Neurology; Peripheral Vascular Disease
SC Neurosciences & Neurology; Cardiovascular System & Cardiology
GA 897HQ
UT WOS:000300639400031
PM 22343640
ER
PT J
AU Jette, AM
Ni, PS
Rasch, EK
Appelman, J
Sandel, ME
Terdiman, J
Chan, LT
AF Jette, Alan M.
Ni, Pengsheng
Rasch, Elizabeth K.
Appelman, Jed
Sandel, M. Elizabeth
Terdiman, Joseph
Chan, Leighton
TI Evaluation of Patient and Proxy Responses on the Activity Measure for
Postacute Care
SO STROKE
LA English
DT Article
DE disability evaluation; rehabilitation; stroke assessment; stroke outcome
ID QUALITY-OF-LIFE; STROKE IMPACT SCALE; PATIENTS PERCEPTIONS; FUNCTIONAL
STATUS; AGREEMENT; ASSESSMENTS; APHASIA; INDEX; EQ-5D
AB Background and Purpose-Our objective was to examine the agreement between adult patients with stroke and family member or clinician proxies in activity measure for postacute care (AM-PAC) summary scores for daily activity, basic mobility, and applied cognitive function.
Methods-This study involved 67 patients with stroke admitted to a hospital within the Kaiser Permanente of Northern California system and were participants in a parent study on stroke outcomes. Each participant and proxy respondent completed the AM-PAC by personal or telephone interview at the point of hospital discharge or during >= 1 transitions to different postacute care settings.
Results-The results suggest that for patients with a stroke proxy, AM-PAC data are robust for family or clinician proxy assessment of basic mobility function and clinician proxy assessment of daily activity function, but less robust for family proxy assessment of daily activity function and for all proxy groups' assessments of applied cognitive function. The pattern of disagreement between patient and proxy was, on average, relatively small and random. There was little evidence of systematic bias between proxy and patient reports of their functional status. The degree of concordance between patient and proxy was similar for those with moderate to severe strokes compared with mild strokes.
Conclusions-Patient and proxy ratings on the AM-PAC achieved adequate agreement for use in stroke research when using proxy respondents could reduce sample selection bias. The AM-PAC data can be implemented across institutional as well as community care settings while achieving precision and reducing respondent burden. (Stroke. 2012;43:824-829.)
C1 [Jette, Alan M.; Ni, Pengsheng] Boston Univ, Sch Publ Hlth, Hlth & Disabil Res Inst, Boston, MA 02118 USA.
[Rasch, Elizabeth K.; Chan, Leighton] NIH, Dept Rehabil Med, Mark O Hatfield Clin Res Ctr, Bethesda, MD 20892 USA.
[Sandel, M. Elizabeth] Kaiser Fdn, Rehabil Ctr, Napa Solano Serv Area, Vallejo, CA USA.
[Terdiman, Joseph] Kaiser Permanente, Div Res, Oakland, CA USA.
RP Jette, AM (reprint author), Boston Univ, Sch Publ Hlth, Hlth & Disabil Res Inst, Med Campus,715 Albany St,T5W, Boston, MA 02118 USA.
EM Ajette@bu.edu
OI Jette, Alan/0000-0002-2117-9973; Ni, Pengsheng/0000-0003-1774-2185
FU National Institutes of Health; American Recovery and Reinvestment Act
grant [1RC1NS068397]
FX This research was supported, in part, by the National Institutes of
Health Intramural Research Program. It was also supported by an American
Recovery and Reinvestment Act grant to Kaiser Permanente, number
1RC1NS068397.
NR 35
TC 11
Z9 11
U1 0
U2 10
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0039-2499
J9 STROKE
JI Stroke
PD MAR
PY 2012
VL 43
IS 3
BP 824
EP 829
DI 10.1161/STROKEAHA.111.619643
PG 6
WC Clinical Neurology; Peripheral Vascular Disease
SC Neurosciences & Neurology; Cardiovascular System & Cardiology
GA 897HQ
UT WOS:000300639400042
PM 22343646
ER
PT J
AU Kitano, M
Rahbari, R
Patterson, EE
Steinberg, SM
Prasad, NB
Wang, YC
Zeiger, MA
Kebebew, E
AF Kitano, Mio
Rahbari, Reza
Patterson, Erin E.
Steinberg, Seth M.
Prasad, Nijaguna B.
Wang, Yongchun
Zeiger, Martha A.
Kebebew, Electron
TI Evaluation of Candidate Diagnostic MicroRNAs in Thyroid Fine-Needle
Aspiration Biopsy Samples
SO THYROID
LA English
DT Article
ID GROWTH-FACTOR RECEPTOR; EXPRESSION PROFILES; CANCER; CARCINOMA; NODULES;
AGGRESSIVENESS; TUMORIGENESIS; MANAGEMENT; PATHWAY; TARGETS
AB Background: Thyroid cancer diagnosis in the United States has increased by 2.3-folds in the last three decades. Up to 30% of thyroid fine-needle aspiration biopsy (FNAB) results are inconclusive. Several differentially expressed microRNAs (miRNAs) have been identified as candidate diagnostic markers for thyroid nodules. We hypothesized that these differentially expressed miRNAs may improve the accuracy of FNAB in difficult to diagnose thyroid nodules.
Methods: Expression levels of four miRNAs (miR-7, -126, -374a, and let-7g) were analyzed using quantitative real-time reverse transcription-polymerase chain reaction in 95 FNAB samples as the training set. A predictor model was formulated based on the most differentially expressed miRNA (miR-7) Delta Ct value and the model was applied on a separate cohort of 59 FNAB samples as the validation set.
Results: miR-7 was the best predictor to distinguish benign from malignant thyroid FNAB samples. The other three miRNAs were co-expressed and did not significantly contribute to the predictor model. miR-7 had a sensitivity of 100%, specificity of 29%, positive predictive value (PPV) of 36%, negative predictive value (NPV) of 100%, and overall accuracy of 76% when applied to the validation set. In subgroup analysis of preoperative nondiagnostic, indeterminate, or suspicious FNAB samples, the predictor model had an overall accuracy of 37% with sensitivity of 100%, specificity of 20%, PPV of 25%, and NPV of 100%.
Conclusions: miR-7 may be a helpful adjunct marker to thyroid FNAB in tumor types which are inconclusive. Given the high NPV of miR-7, a patient with a benign result based on the predictor model may be followed as opposed to performing an immediate diagnostic thyroidectomy. Future prospective clinical trials evaluating its accuracy in a larger cohort are warranted to determine its clinical utility.
C1 [Kebebew, Electron] NCI, Endocrine Oncol Sect, Surg Branch, NIH,CRC, Bethesda, MD 20892 USA.
[Prasad, Nijaguna B.; Wang, Yongchun; Zeiger, Martha A.] Johns Hopkins Univ, Sch Med, Dept Surg, Endocrine Surg Sect, Baltimore, MD 21205 USA.
RP Kebebew, E (reprint author), NCI, Endocrine Oncol Sect, Surg Branch, NIH,CRC, 10 Ctr Dr, Bethesda, MD 20892 USA.
EM kebebewe@mail.nih.gov
FU Center for Cancer Research, National Cancer Institute, National
Institutes of Health
FX This research was supported by the Intramural Research Program, Center
for Cancer Research, National Cancer Institute, National Institutes of
Health.
NR 42
TC 38
Z9 39
U1 0
U2 6
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 MAR
PY 2012
VL 22
IS 3
BP 285
EP 291
DI 10.1089/thy.2011.0313
PG 7
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 902MF
UT WOS:000301041700008
PM 22304369
ER
PT J
AU Cheng, TJ
Li, QL
Zhou, ZG
Wang, YL
Bryant, SH
AF Cheng, Tiejun
Li, Qingliang
Zhou, Zhigang
Wang, Yanli
Bryant, Stephen H.
TI Structure-Based Virtual Screening for Drug Discovery: a Problem-Centric
Review
SO AAPS JOURNAL
LA English
DT Review
DE docking; machine learning; structure-based virtual scoring;
target-biased scoring function
ID PROTEIN-LIGAND INTERACTIONS; BINDING-AFFINITY PREDICTION; EMPIRICAL
SCORING FUNCTIONS; HIGH-THROUGHPUT DOCKING; MOLECULAR DOCKING; FLEXIBLE
DOCKING; KINASE INHIBITORS; AUTOMATED DOCKING; GENETIC ALGORITHM;
WATER-MOLECULES
AB Structure-based virtual screening (SBVS) has been widely applied in early-stage drug discovery. From a problem-centric perspective, we reviewed the recent advances and applications in SBVS with a special focus on docking-based virtual screening. We emphasized the researchers' practical efforts in real projects by understanding the ligand-target binding interactions as a premise. We also highlighted the recent progress in developing target-biased scoring functions by optimizing current generic scoring functions toward certain target classes, as well as in developing novel ones by means of machine learning techniques.
C1 [Cheng, Tiejun; Li, Qingliang; Zhou, Zhigang; Wang, Yanli; Bryant, Stephen H.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA.
RP Wang, YL (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, 8600 Rockville Pike, Bethesda, MD 20894 USA.
EM ywang@ncbi.nlm.nih.gov; bryant@ncbi.nlm.nih.gov
RI Cheng, Tiejun/A-5344-2010; Li, Qingliang/N-5169-2015
OI Cheng, Tiejun/0000-0002-4486-3356; Li, Qingliang/0000-0002-6453-236X
FU National Institutes of Health (NIH), National Library of Medicine (NLM)
FX We thank the Intramural Research Program of the National Institutes of
Health (NIH), National Library of Medicine (NLM) for funding support.
NR 97
TC 127
Z9 130
U1 9
U2 96
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1550-7416
J9 AAPS J
JI AAPS J.
PD MAR
PY 2012
VL 14
IS 1
BP 133
EP 141
DI 10.1208/s12248-012-9322-0
PG 9
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 896GP
UT WOS:000300554000015
PM 22281989
ER
PT J
AU Song, R
Yang, RF
Wu, N
Su, RB
Li, J
Peng, XQ
Li, X
Gaal, J
Xi, ZX
Gardner, EL
AF Song, Rui
Yang, Ri-Fang
Wu, Ning
Su, Rui-Bin
Li, Jin
Peng, Xiao-Qing
Li, Xia
Gaal, Jozsef
Xi, Zheng-Xiong
Gardner, Eliot L.
TI YQA14: a novel dopamine D-3 receptor antagonist that inhibits cocaine
self-administration in rats and mice, but not in D-3 receptor-knockout
mice
SO ADDICTION BIOLOGY
LA English
DT Article
DE Cocaine; D-3 receptor; dopamine; SB-277011A; self-administration; YQA14
ID DRUG-SEEKING BEHAVIOR; CONDITIONED PLACE PREFERENCE; ENHANCED BRAIN
REWARD; PROGRESSIVE-RATIO; INDUCED REINSTATEMENT; HIGH-AFFINITY;
PHARMACOLOGICAL ACTIONS; SELECTIVE ANTAGONISM; REINFORCING EFFICACY;
TRIGGERED RELAPSE
AB The dopamine (DA) D3 receptor is posited to be importantly involved in drug reward and addiction, and D3 receptor antagonists have shown extraordinary promise as potential anti-addiction pharmacotherapeutic agents in animal models of drug addiction. SB-277011A is the best characterized D3 receptor antagonist in such models. However, the potential use of SB-277011A in humans is precluded by pharmacokinetic and toxicity problems. We here report a novel D3 receptor antagonist YQA14 that shows similar pharmacological properties as SB-277011A. In vitro receptor binding assays suggest that YQA14 has two binding sites on human cloned D3 receptors with Ki-High (0.68 x 10(4) nM) and Ki-Low (2.11 nM), and displays > 150-fold selectivity for D3 over D2 receptors and > 1000-fold selectivity for D3 over other DA receptors. Systemic administration of YQA14 (6.25-25 mg/kg) or SB-277011A (12.5-25 mg/kg) significantly and dose-dependently reduced intravenous cocaine self-administration under both low fixed-ratio and progressive-ratio reinforcement conditions in rats, while failing to alter oral sucrose self-administration and locomotor activity, suggesting a selective inhibition of drug reward. However, when the drug dose was increased to 50 mg/kg, YQA14 and SB-277011A significantly inhibited basal and cocaine-enhanced locomotion in rats. Finally, both D3 antagonists dose-dependently inhibited intravenous cocaine self-administration in wild-type mice, but not in D3 receptor-knockout mice, suggesting that their action is mediated by D3 receptor blockade. These findings suggest that YQA14 has a similar anti-addiction profile as SB-277011A, and deserves further study and development.
C1 [Song, Rui; Peng, Xiao-Qing; Li, Xia; Xi, Zheng-Xiong; Gardner, Eliot L.] Natl Inst Drug Abuse, Intramural Res Program, Baltimore, MD USA.
[Song, Rui; Yang, Ri-Fang; Wu, Ning; Su, Rui-Bin; Li, Jin] Beijing Inst Pharmacol & Toxicol, Beijing, Peoples R China.
RP Xi, ZX (reprint author), Natl Inst Drug Abuse, Intramural Res Program, Baltimore, MD USA.
EM lijin@nic.bmi.ac.cn; zxi@intra.nida.nih.gov
OI Yang, Rifang/0000-0001-8087-9614; PENG, XIAOQING/0000-0002-7272-5428
FU US National Institute on Drug Abuse Intramural Research Program;
National Basic Research Program of China [2009CB522008]; National Key
Technology Research and Development Program of China [2007BAI07B02]
FX This work was supported by the US National Institute on Drug Abuse
Intramural Research Program (for the in vivo behavioral studies) and the
National Basic Research Program of China (No. 2009CB522008) and the
National Key Technology Research and Development Program of China (No.
2007BAI07B02) (for the in vitro binding assays). We thank Dr Xue- Chu
Zhen for providing us with DA D1-, D2- and
D5-transfected cells we used in these experiments.
NR 62
TC 44
Z9 46
U1 2
U2 10
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1355-6215
J9 ADDICT BIOL
JI Addict. Biol.
PD MAR
PY 2012
VL 17
IS 2
BP 259
EP 273
DI 10.1111/j.1369-1600.2011.00317.x
PG 15
WC Biochemistry & Molecular Biology; Substance Abuse
SC Biochemistry & Molecular Biology; Substance Abuse
GA 896LT
UT WOS:000300568500005
PM 21507153
ER
PT J
AU Gilman, JM
Smith, AR
Ramchandani, VA
Momenan, R
Hommer, DW
AF Gilman, Jodi M.
Smith, Ashley R.
Ramchandani, Vijay A.
Momenan, Reza
Hommer, Daniel W.
TI The effect of intravenous alcohol on the neural correlates of risky
decision making in healthy social drinkers
SO ADDICTION BIOLOGY
LA English
DT Article
DE Alcohol; imaging; impulsivity; nucleus accumbens; reward; risk taking
ID NUCLEUS-ACCUMBENS; FAMILY HISTORY; PREFRONTAL CORTEX; BINGE DRINKING;
MG-PERCENT; ETHANOL; MODEL; IMPAIRMENT; BEHAVIOR; IMPULSIVITY
AB Alcohol is thought to contribute to an increase in risk-taking behavior, but the neural correlates underlying this effect are not well understood. In this study, participants were given intravenous alcohol or placebo while undergoing functional magnetic resonance imaging (fMRI) and playing a risk-taking game. The game allowed us to examine the neural response to choosing a safe or risky option, anticipating outcome and receiving feedback. We found that alcohol increased risk-taking behavior, particularly among participants who experienced more stimulating effects of alcohol. fMRI scans demonstrated that alcohol increased activation in the striatum to risky compared with safe choices and dampened the neural response to notification of both winning and losing throughout the caudate, thalamus and insula. This study suggests that alcohol may increase risk-taking behavior by both activating brain regions involved in reward when a decision is made, and dampening the response to negative and positive feedback.
C1 [Gilman, Jodi M.; Smith, Ashley R.; Ramchandani, Vijay A.; Momenan, Reza; Hommer, Daniel W.] NIAAA, Sect Brain Electrophysiol & Imaging, Lab Clin & Translat Studies, NIH, Bethesda, MD USA.
RP Gilman, JM (reprint author), 10 Ctr Dr,Bldg 10 CRC Hatfield Clinical Res Ctr,R, Bethesda, MD 20892 USA.
EM gilmanj@mail.nih.gov
FU Intramural NIH HHS [ZIA AA000466-06]
NR 61
TC 18
Z9 19
U1 1
U2 11
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1355-6215
J9 ADDICT BIOL
JI Addict. Biol.
PD MAR
PY 2012
VL 17
IS 2
BP 465
EP 478
DI 10.1111/j.1369-1600.2011.00383.x
PG 14
WC Biochemistry & Molecular Biology; Substance Abuse
SC Biochemistry & Molecular Biology; Substance Abuse
GA 896LT
UT WOS:000300568500021
PM 21995446
ER
PT J
AU Hirsch, CH
Buzkova, P
Robbins, JA
Patel, KV
Newman, AB
AF Hirsch, Calvin Hayes
Buzkova, Petra
Robbins, John A.
Patel, Kushang V.
Newman, Anne B.
TI Predicting late-life disability and death by the rate of decline in
physical performance measures(dagger)
SO AGE AND AGEING
LA English
DT Article
DE ageing; motor skills; activities of daily living; disabled persons;
mortality; elderly
ID WHITE-MATTER ABNORMALITIES; FUNCTIONING OLDER-ADULTS; LOWER-EXTREMITY
FUNCTION; INCIDENT DISABILITY; MOTOR FUNCTION; WALKING SPEED; GAIT
SPEED; MORTALITY; RISK; ASSOCIATION
AB Background: the rate of performance decline may influence the risk of disability or death.
Methods: for 4,182 Cardiovascular Health Study participants, we used multinomial Poisson log-linear models to assess the contribution of physical performance in 1998-99, and the rate of performance change between 1992-93 and 1998-99, to the risk of death or disability in 2005-06 in three domains: mobility, upper-extremity function (UEF) and activities of daily living (ADL). We evaluated performance in finger-tapping, grip strength, stride length, gait speed and chair stands separately and together for each outcome, adjusting for age, gender, race and years of disability in that outcome between 1992-93 and 1998-99.
Results: participants' age averaged 79.4 in 1998-99; 1,901 died over 7 years. Compared with the lowest change quintile in stride length, the highest quintile had a 1.32 relative risk (RR) of ADL disability (95% CI: 1.16 -1.96) and a 1.27 RR of death (95% CI: 1.07 -1.51). The highest change quintile for grip strength increased the risk of ADL disability by 35% (95% CI: 1.13 -1.61) and death by 31% (95% CI: 1.16 -1.49), compared with the lowest quintile. The annual change in stride length and grip strength also predicted disability in mobility and UEF.
Conclusion: performance trajectories independently predict death and disability.
C1 [Hirsch, Calvin Hayes; Robbins, John A.] Univ Calif Davis, Davis Med Ctr, Div Gen Med, Sacramento, CA 95817 USA.
[Buzkova, Petra] Univ Washington, Dept Biostat, Seattle, WA 98195 USA.
[Patel, Kushang V.] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
[Newman, Anne B.] Univ Pittsburgh, Grad Sch Publ Hlth, Piottsburgh, PA USA.
RP Hirsch, CH (reprint author), Univ Calif Davis, Davis Med Ctr, Div Gen Med, 4150 V St,PSSB Suite 2400, Sacramento, CA 95817 USA.
EM chhirsch@ucdavis.edu
RI Newman, Anne/C-6408-2013
OI Newman, Anne/0000-0002-0106-1150
FU National Institute on Aging [AG-023629, R01 AG-15928, R01 AG-20098,
AG-027058]; National Institute on Aging, National Institutes of Health;
National Heart, Lung, and Blood Institute [N01-HC-85079, N01-HC-85086,
N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133,
U01 HL080295, R01 HL-075366]; University of Pittsburgh Claude. D. Pepper
Older Americans Independence Center [P30-AG-024827]
FX The research reported in this article was supported in part by the
National Institute on Aging AG-023629 and in part by the Intramural
Research Program of the National Institute on Aging, National Institutes
of Health. CHS was supported by contract numbers N01-HC-85079 through
N01-HC-85086, N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150,
N01-HC-45133, grant number U01 HL080295 from the National Heart, Lung,
and Blood Institute, with additional contribution from the National
Institute of Neurological Disorders and Stroke. Additional support was
provided through R01 AG-15928, R01 AG-20098, and AG-027058 from the
National Institute on Aging, R01 HL-075366 from the National Heart, Lung
and Blood Institute, and the University of Pittsburgh Claude. D. Pepper
Older Americans Independence Center P30-AG-024827. A full list of
principal CHS investigators and institutions can be found at
http://www.chs-nhlbi.org/pi.htm.
NR 27
TC 17
Z9 17
U1 1
U2 12
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0002-0729
J9 AGE AGEING
JI Age Ageing
PD MAR
PY 2012
VL 41
IS 2
BP 155
EP 161
DI 10.1093/ageing/afr151
PG 7
WC Geriatrics & Gerontology
SC Geriatrics & Gerontology
GA 895HS
UT WOS:000300487600004
PM 22156556
ER
PT J
AU Choi, S
McAleer, JP
Zheng, M
Deleo, FR
Ouyang, W
Hooper, LV
Qin, S
Reinhart, TA
Kolls, JK
AF Choi, S.
McAleer, J. P.
Zheng, M.
DeLeo, F. R.
Ouyang, W.
Hooper, L. V.
Qin, S.
Reinhart, T. A.
Kolls, J. K.
TI Acute alcohol inhibits STAT3 induction of Reg3 gamma in MRSA Pneumonia
SO ALCOHOL
LA English
DT Meeting Abstract
CT Meeting of the Alcohol-and-Immunology-Research-Interest-Group on Alcohol
and Epigenetic Changes (AIRIG)
CY NOV 18, 2011
CL Loyola Univ Med Ctr, Maywood, IL
SP Alcohol & Immunol Res Interest Grp (AIRIG)
HO Loyola Univ Med Ctr
C1 [Choi, S.; McAleer, J. P.; Kolls, J. K.] LSUHSC, New Orleans, LA USA.
[DeLeo, F. R.] NIAID, Rocky Mt, MT USA.
[Ouyang, W.] Genentech San Francisco, San Francisco, CA USA.
[Hooper, L. V.] UT SW Dallas, Dallas, TX USA.
[Qin, S.; Reinhart, T. A.] U Pittsburgh, Pittsburgh, PA 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
J9 ALCOHOL
JI Alcohol
PD MAR
PY 2012
VL 46
IS 2
MA 5
BP 175
EP 175
PG 1
WC Substance Abuse; Pharmacology & Pharmacy; Toxicology
SC Substance Abuse; Pharmacology & Pharmacy; Toxicology
GA 898RW
UT WOS:000300760500013
ER
PT J
AU O'Seaghdha, CM
Lyass, A
Massaro, JM
Meigs, JB
Coresh, J
D'Agostino, RB
Astor, BC
Fox, CS
AF O'Seaghdha, Conall M.
Lyass, Asya
Massaro, Joseph M.
Meigs, James B.
Coresh, Josef
D'Agostino, Ralph B., Sr.
Astor, Brad C.
Fox, Caroline S.
TI A Risk Score for Chronic Kidney Disease in the General Population
SO AMERICAN JOURNAL OF MEDICINE
LA English
DT Article
DE Chronic kidney disease; CKD; Risk score
ID GLOMERULAR-FILTRATION-RATE; CORONARY-HEART-DISEASE; IMPROVING GLOBAL
OUTCOMES; ATHEROSCLEROSIS RISK; POSITION STATEMENT; SERUM CREATININE;
RENAL-DISEASE; PREDICTION; COMMUNITIES; PROGRESSION
AB BACKGROUND: Stratification of individuals at risk for chronic kidney disease may allow optimization of preventive measures to reduce disease incidence and complications. We sought to develop a risk score that estimates an individual's absolute risk of incident chronic kidney disease.
METHODS: Framingham Heart Study participants free of baseline chronic kidney disease, who attended a baseline examination in 1995-1998 and follow-up in 2005-2008, were included in the analysis (n = 2490). Chronic kidney disease was defined as an estimated glomerular filtration rate <60 mL/min/1.73m(2) using the Modification of Diet in Renal Disease equation. Participants were assessed for the development of chronic kidney disease at 10 years follow-up. Stepwise logistic regression was used to identify chronic kidney disease risk factors, and these were used to construct a risk score predicting 10-year chronic kidney disease risk. Performance characteristics were assessed using calibration and discrimination measures. The final model was externally validated in the bi-ethnic Atherosclerosis Risk in Communities Study (n = 1777).
RESULTS: There were 1171 men and 1319 women at baseline, and the mean age was 57.1 years. At follow-up, 9.2% (n = 229) had developed chronic kidney disease. Age, diabetes, hypertension, baseline estimated glomerular filtration rate, and albuminuria were independently associated with incident chronic kidney disease (P < .05), and these covariates were incorporated into a risk function (c-statistic 0.813). In external validation in the ARIC study, the c-statistic was 0.74 in whites (n = 1353) and 0.75 in blacks (n = 424).
CONCLUSION: Risk stratification for chronic kidney disease is achievable using a risk score derived from clinical factors that are readily accessible in primary care. The utility of this score in identifying individuals in the community at high risk of chronic kidney disease warrants further investigation. Published by Elsevier Inc. . The American Journal of Medicine (2012) 125, 270-277
C1 [O'Seaghdha, Conall M.; Fox, Caroline S.] NHLBI, Framingham Heart Study, Framingham, MA 01702 USA.
[O'Seaghdha, Conall M.; Fox, Caroline S.] Ctr Populat Studies, Framingham, MA USA.
[O'Seaghdha, Conall M.] Massachusetts Gen Hosp, Div Renal, Brigham & Womens Hosp, Boston, MA 02114 USA.
[O'Seaghdha, Conall M.; Meigs, James B.; Fox, Caroline S.] Harvard Univ, Sch Med, Boston, MA USA.
[Lyass, Asya; D'Agostino, Ralph B., Sr.] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA.
[Massaro, Joseph M.] Boston Univ, Dept Biostat, Sch Publ Hlth, Boston, MA 02215 USA.
[Meigs, James B.] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA.
[Coresh, Josef; Astor, Brad C.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA.
[Coresh, Josef; Astor, Brad C.] Johns Hopkins Univ, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD USA.
[Coresh, Josef; Astor, Brad C.] Johns Hopkins Univ, Sch Med, Dept Med, Div Gen Internal Med, Baltimore, MD 21205 USA.
[Coresh, Josef] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD USA.
[Fox, Caroline S.] Brigham & Womens Hosp, Div Endocrinol, Boston, MA 02115 USA.
RP Fox, CS (reprint author), NHLBI, Framingham Heart Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA.
EM foxca@nhlbi.nih.gov
OI Massaro, Joseph/0000-0002-2682-4812
FU National Heart, Lung, and Blood Institute [N01-HC-25195, N01-HC-55015,
N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021,
N01-HC-55022]; National Institute of Diabetes and Digestive and Kidney
Diseases [1 R01 DK076770-01]; [U01HL075572-01]
FX The Framingham Heart Study is supported by the National Heart, Lung, and
Blood Institute (N01-HC-25195); urinary albumin excretion assay reagents
were donated by Roche Diagnostics Inc. The Atherosclerosis Risk in
Communities (ARIC) Study is carried out as a collaborative study
supported by National Heart, Lung, and Blood Institute contracts
N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020,
N01-HC-55021, and N01-HC-55022, with the ARIC Carotid MRI Study funded
by U01HL075572-01. Drs Astor and Coresh are supported by the National
Institute of Diabetes and Digestive and Kidney Diseases (1 R01
DK076770-01).
NR 39
TC 16
Z9 16
U1 0
U2 11
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0002-9343
J9 AM J MED
JI Am. J. Med.
PD MAR
PY 2012
VL 125
IS 3
BP 270
EP 277
DI 10.1016/j.amjmed.2011.09.009
PG 8
WC Medicine, General & Internal
SC General & Internal Medicine
GA 897BI
UT WOS:000300615400020
PM 22340925
ER
PT J
AU Scliar, MO
Soares-Souza, GB
Chevitarese, J
Lemos, L
Magalhaes, WCS
Fagundes, NJ
Bonatto, SL
Yeager, M
Chanock, SJ
Tarazona-Santos, E
AF Scliar, Marilia O.
Soares-Souza, Giordano B.
Chevitarese, Juliana
Lemos, Livia
Magalhaes, Wagner C. S.
Fagundes, Nelson J.
Bonatto, Sandro L.
Yeager, Meredith
Chanock, Stephen J.
Tarazona-Santos, Eduardo
TI The population genetics of quechuas, the largest native south american
group: Autosomal sequences, SNPs, and microsatellites evidence high
level of diversity
SO AMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY
LA English
DT Article
DE native American; Andes; microsatellites; autosomal noncoding sequence;
HGDP-CEPH
ID MITOCHONDRIAL-DNA DIVERSITY; MULTILOCUS GENOTYPE DATA; GENOME-WIDE
PATTERNS; AMERINDIAN POPULATIONS; CENTRAL ANDES; ADMIXTURE;
POLYMORPHISM; FREQUENCIES; MARKERS; MODELS
AB Elucidating the pattern of genetic diversity for non-European populations is necessary to make the benefits of human genetics research available to individuals from these groups. In the era of large human genomic initiatives, Native American populations have been neglected, in particular, the Quechua, the largest South Amerindian group settled along the Andes. We characterized the genetic diversity of a Quechua population in a global setting, using autosomal noncoding sequences (nine unlinked loci for a total of 16 kb), 351 unlinked SNPs and 678 microsatellites and tested predictions of the model of the evolution of Native Americans proposed by (Tarazona-Santos et al.: Am J Hum Genet 68 (2001) 14851496). European admixture is <5% and African ancestry is barely detectable in the studied population. The largest genetic distances were between African versus Quechua or Melanesian populations, which is concordant with the African origin of modern humans and the fact that South America was the last part of the world to be peopled. The diversity in the Quechua population is comparable with that of Eurasian populations, and the allele frequency spectrum based on resequencing data does not reflect a reduction in the proportion of rare alleles. Thus, the Quechua population is a large reservoir of common and rare genetic variants of South Amerindians. These results are consistent with and complement our evolutionary model of South Amerindians (Tarazona-Santos et al.: Am J Hum Genet 68 (2001) 14851496), proposed based on Y-chromosome data, which predicts high genomic diversity due to the high level of gene flow between Andean populations and their long-term effective population size. Am J Phys Anthropol 2012. (c) 2012 Wiley Periodicals, Inc.
C1 [Scliar, Marilia O.; Soares-Souza, Giordano B.; Chevitarese, Juliana; Lemos, Livia; Magalhaes, Wagner C. S.; Tarazona-Santos, Eduardo] Univ Fed Minas Gerais, Inst Ciencias Biol, Dept Biol Geral, BR-31270910 Belo Horizonte, MG, Brazil.
[Fagundes, Nelson J.] Univ Fed Rio Grande do Sul, Inst Biociencias, Dept Genet, BR-91501970 Porto Alegre, RS, Brazil.
[Bonatto, Sandro L.] Pontificia Univ Catolica Rio Grande do Sul, Fac Biociencias, BR-90619900 Porto Alegre, RS, Brazil.
[Yeager, Meredith] NCI, Intramural Res Support Program, SAIC Frederick, FCRDC, Frederick, MD 21702 USA.
[Yeager, Meredith] NCI, Core Genotype Facil, NIH, Gaithersburg, MD 20877 USA.
[Chanock, Stephen J.] NCI, Lab Translat Genom, Div Canc Epidemiol & Genet, NIH, Gaithersburg, MD 20877 USA.
RP Tarazona-Santos, E (reprint author), Univ Fed Minas Gerais, Inst Ciencias Biol, Dept Biol Geral, Av Antonio Carlos 6627,Pampulha Caixa Postal 486, BR-31270910 Belo Horizonte, MG, Brazil.
EM edutars@icb.ufmg.br
RI Magalhaes, Wagner/D-8822-2015; Bonatto, Sandro/A-1240-2010
OI Bonatto, Sandro/0000-0002-0064-467X
FU Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (Brazil);
Fundacao de Amparo a Pesquisa de Minas Gerais (Brazil); Brazilian
Ministry of Education (Agency for the Development of Graduate
Education-CAPES); National Cancer Institute
FX Grant sponsors: Conselho Nacional de Desenvolvimento Cientifico e
Tecnologico (Brazil), Fundacao de Amparo a Pesquisa de Minas Gerais
(Brazil), Brazilian Ministry of Education (Agency for the Development of
Graduate Education-CAPES) and National Cancer Institute.
NR 72
TC 7
Z9 7
U1 2
U2 8
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0002-9483
J9 AM J PHYS ANTHROPOL
JI Am. J. Phys. Anthropol.
PD MAR
PY 2012
VL 147
IS 3
BP 443
EP 451
DI 10.1002/ajpa.22013
PG 9
WC Anthropology; Evolutionary Biology
SC Anthropology; Evolutionary Biology
GA 894TH
UT WOS:000300449300011
PM 22282032
ER
PT J
AU Molica, F
Matter, CM
Burger, F
Pelli, G
Lenglet, S
Zimmer, A
Pacher, P
Steffens, S
AF Molica, Filippo
Matter, Christian M.
Burger, Fabienne
Pelli, Graziano
Lenglet, Sebastien
Zimmer, Andreas
Pacher, Pal
Steffens, Sabine
TI Cannabinoid receptor CB2 protects against balloon-induced neointima
formation
SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY
LA English
DT Article
DE restenosis; smooth muscle cells; macrophages
ID HEPATIC ISCHEMIA/REPERFUSION INJURY; CORONARY STENT THROMBOSIS;
DRUG-ELUTING STENTS; APOE-KNOCKOUT MICE; ENDOCANNABINOID SYSTEM;
MULTIPLE-SCLEROSIS; ATHEROSCLEROSIS; MIGRATION; INFLAMMATION; ACTIVATION
AB Molica F, Matter CM, Burger F, Pelli G, Lenglet S, Zimmer A, Pacher P, Steffens S. Cannabinoid receptor CB2 protects against balloon-induced neointima formation. Am J Physiol Heart Circ Physiol 302: H1064-H1074, 2012. First published January 6, 2012; doi:10.1152/ajpheart.00444.2011.-Cannabinoid receptor CB2 activation inhibits inflammatory proliferation and migration of vascular smooth muscle cells in vitro. The potential in vivo relevance of these findings is unclear. We performed carotid balloon distension injury in hypercholesterolemic apolipoprotein E knockout (ApoE(-/-)) mice receiving daily intraperitoneal injection of the CB2 agonist JWH133 (5 mg/kg) or vehicle, with the first injection given 30 min before injury. Alternatively, we subjected CB2-/- and wild-type (WT) mice to balloon injury. We determined CB2 mRNA and protein expression in dilated arteries of ApoE(-/-) mice. Neointima formation was assessed histologically. We used bone marrow-derived murine CB2-/- and WT macrophages to study adhesion to plastic, fibronectin, or collagen, and migration was assayed by modified Boyden chamber. Aortic smooth muscle cells were isolated to determine in vitro proliferation rates. We found increased vascular CB2 expression in ApoE(-/-) mice in response to balloon injury. Seven to twenty-one days after dilatation, injured vessels of JWH133-treated mice had less intimal nuclei numbers as well as intimal and medial areas, associated with less staining for proliferating cells, smooth muscle cells, and macrophages. Complete endothelial repair was observed after 14 days in both JWH133- and vehicle-treated mice. CB2 deficiency resulted in increased intima formation compared with WT, whereas JWH133 did not affect intimal formation in CB2-/- mice. Apoptosis rates assessed by in situ terminal deoxynucleotidyl transferase dUTP-mediated nick-end labeling staining 1 h postballooning were significantly higher in the CB2 knockouts. In vitro, bone marrow-derived CB2-/- macrophages showed enhanced adherence and migration compared with WT cells and elevated mRNA levels of adhesion molecules, chemokine receptors CCR1 and 5, and chemokine CCL2. Proliferation rates were significantly increased in CB2-/- smooth muscle cells compared with WT. In conclusion, pharmacological activation or genetic deletion of CB2 receptors modulate neointima formation via protective effects in macrophages and smooth muscle cells.
C1 [Molica, Filippo; Burger, Fabienne; Pelli, Graziano; Lenglet, Sebastien; Steffens, Sabine] Univ Hosp Geneva, Dept Internal Med, Div Cardiol, Geneva, Switzerland.
[Matter, Christian M.] Univ Zurich, Inst Physiol, Zurich Ctr Integrat Human Physiol, Zurich, Switzerland.
[Matter, Christian M.] Univ Zurich Hosp, CH-8091 Zurich, Switzerland.
[Zimmer, Andreas] Univ Bonn, Inst Mol Psychiat, Bonn, Germany.
[Pacher, Pal] NIAAA, Sect Oxidat Stress Tissue Injury, Lab Physiol Studies, Bethesda, MD USA.
RP Steffens, S (reprint author), Fdn Med Res, Univ Hosp, Dept Med, Div Cardiol, 64 Ave Roseraie, CH-1211 Geneva, Switzerland.
EM sabine.steffens@unige.ch
RI Pacher, Pal/B-6378-2008; Zimmer, Andreas/B-8357-2009; LENGLET,
Sebastien/N-8923-2013; Filippo, Molica/A-6315-2013
OI Pacher, Pal/0000-0001-7036-8108; LENGLET, Sebastien/0000-0002-4853-8163;
FU Swiss National Science Foundation [310030-116324, 310030-130732]; Swiss
Life; OPO Foundation; Prevot
FX This work was supported by Swiss National Science Foundation Grants
310030-116324 and 310030-130732, Swiss Life, Prevot, and OPO Foundation
(to S. Steffens).
NR 41
TC 11
Z9 11
U1 0
U2 3
PU AMER PHYSIOLOGICAL SOC
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA
SN 0363-6135
J9 AM J PHYSIOL-HEART C
JI Am. J. Physiol.-Heart Circul. Physiol.
PD MAR
PY 2012
VL 302
IS 5
BP H1064
EP H1074
DI 10.1152/ajpheart.00444.2011
PG 11
WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular
Disease
SC Cardiovascular System & Cardiology; Physiology
GA 898EX
UT WOS:000300720500004
PM 22227125
ER
PT J
AU Glasgow, RE
AF Glasgow, Russell E.
TI Estimating Population Impact
SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE
LA English
DT Letter
C1 NCI, Implementat Sci Div Canc Control & Populat Sci, Rockville, MD USA.
RP Glasgow, RE (reprint author), NCI, Implementat Sci Div Canc Control & Populat Sci, Rockville, MD USA.
EM glasgowre@mail.nih.gov
NR 5
TC 0
Z9 0
U1 0
U2 0
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0749-3797
J9 AM J PREV MED
JI Am. J. Prev. Med.
PD MAR
PY 2012
VL 42
IS 3
BP E30
EP E31
DI 10.1016/j.amepre.2011.12.004
PG 3
WC Public, Environmental & Occupational Health; Medicine, General &
Internal
SC Public, Environmental & Occupational Health; General & Internal Medicine
GA 897CI
UT WOS:000300618600003
PM 22341177
ER
PT J
AU Balansky, R
D'Agostini, F
Micale, RT
La Maestra, S
Steele, VE
De Flora, S
AF Balansky, Roumen
D'Agostini, Francesco
Micale, Rosanna T.
La Maestra, Sebastiano
Steele, Vernon E.
De Flora, Silvio
TI Dose-related cytogenetic damage in pulmonary alveolar macrophages from
mice exposed to cigarette smoke early in life
SO ARCHIVES OF TOXICOLOGY
LA English
DT Article
DE Cigarette smoke; Neonatal mice; Pulmonary alveolar macrophages;
Cytogenetic damage; Micronucleus test
ID GLUTATHIONE-S-TRANSFERASE; VITRO MICRONUCLEUS TEST; N-ACETYLCYSTEINE;
TOBACCO-SMOKE; NEONATAL MICE; LUNG-CANCER; HUMAN-CELLS; MOUSE LUNG;
MODULATION; RISK
AB The micronucleus test detects both structural and numerical chromosomal aberrations caused by environmental agents. However, this test is poorly sensitive to detect the clastogenicity of cigarette smoke (CS) in human peripheral blood lymphocytes. At variance with peripheral blood lymphocytes and other cells outside the lower respiratory tract, pulmonary alveolar macrophages (PAM) are selectively affected by inhalable carcinogens and have been used to evaluate the modulation of CS-related cytogenetic alterations in vivo. The present study was aimed at evaluating (1) the cytogenetic response in PAM isolated from the lung of mice exposed to CS during the first 4 weeks of life and (2) the dose dependence of MN and polynucleated (PN) PAM formation in CS-exposed mice. To this purpose, ICR(CD-1) mice were exposed whole body to mainstream CS for 4 weeks, starting immediately after birth. Bronchoalveolar lavage (BAL) was performed to evaluate the cellularity of this fluid and the frequency of PN and MN PAM. At the doses of 119, 292, and 438 mg/m(3) total particulate matter, CS significantly increased both the proportion of PAM in the BAL fluid and the frequencies of PN and MN PAM. The cytogenetic effects were significantly correlated with the CS dose. In conclusion, PAM are suitable to detect induction by CS of clastogenic and aneugenic effects in mice during a developmental period corresponding to infancy, childhood, and early adolescence in humans. These surrogate cells, providing an important defense mechanism of the respiratory tract, are proposed as indicators of CS-related DNA damage in youngsters.
C1 [D'Agostini, Francesco; Micale, Rosanna T.; La Maestra, Sebastiano; De Flora, Silvio] Univ Genoa, Dept Hlth Sci, I-16132 Genoa, Italy.
[Balansky, Roumen] Natl Oncol Ctr, Sofia 1756, Bulgaria.
[Steele, Vernon E.] NCI, Rockville, MD 20892 USA.
RP De Flora, S (reprint author), Univ Genoa, Dept Hlth Sci, Via A Pastore 1, I-16132 Genoa, Italy.
EM rubalansky@sbaloncology.bg; steelev@mail.nih.gov; sdf@unige.it
FU U.S. National Cancer Institute [NO1-CN53301]; Bulgarian Ministry of
Education, Youth and Science; Hasumi International Research Foundation
(Bulgaria)
FX We thank Dr. Ilaria Righi for her skillful assistance in preparation of
the manuscript. This study was supported by the U.S. National Cancer
Institute (grant NO1-CN53301), the Bulgarian Ministry of Education,
Youth and Science (National Science Fund), and the Hasumi International
Research Foundation (Bulgaria).
NR 54
TC 2
Z9 2
U1 1
U2 4
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 0340-5761
J9 ARCH TOXICOL
JI Arch. Toxicol.
PD MAR
PY 2012
VL 86
IS 3
BP 509
EP 516
DI 10.1007/s00204-011-0765-3
PG 8
WC Toxicology
SC Toxicology
GA 896NX
UT WOS:000300575900016
PM 21989788
ER
PT J
AU Francischetti, IMB
Oliveira, CJ
Ostera, GR
Yager, SB
Debierre-Grockiego, F
Carregaro, V
Jaramillo-Gutierrez, G
Hume, JCC
Jiang, LB
Moretz, SE
Lin, CK
Ribeiro, JMC
Long, CA
Vickers, BK
Schwarz, RT
Seydel, KB
Iacobelli, M
Ackerman, HC
Srinivasan, P
Gomes, RB
Wang, XD
Monteiro, RQ
Kotsyfakis, M
Sa-Nunes, A
Waisberg, M
AF Francischetti, Ivo M. B.
Oliveira, Carlo J.
Ostera, Graciela R.
Yager, Stephanie B.
Debierre-Grockiego, Francoise
Carregaro, Vanessa
Jaramillo-Gutierrez, Giovanna
Hume, Jen C. C.
Jiang, Lubin
Moretz, Samuel E.
Lin, Christina K.
Ribeiro, Jose M. C.
Long, Carole A.
Vickers, Brandi K.
Schwarz, Ralph T.
Seydel, Karl B.
Iacobelli, Massimo
Ackerman, Hans C.
Srinivasan, Prakash
Gomes, Regis B.
Wang, Xunde
Monteiro, Robson Q.
Kotsyfakis, Michail
Sa-Nunes, Anderson
Waisberg, Michael
TI Defibrotide Interferes With Several Steps of the
Coagulation-Inflammation Cycle and Exhibits Therapeutic Potential to
Treat Severe Malaria
SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
LA English
DT Article
DE anticoagulants; blood coagulation; endothelium; microcirculation;
vascular biology
ID FALCIPARUM-INFECTED ERYTHROCYTES; FACTOR PATHWAY INHIBITOR; INNATE
IMMUNE-RESPONSE; DENDRITIC CELLS; VENOOCCLUSIVE DISEASE; ADENOSINE
RECEPTORS; BLOOD-COAGULATION; ENDOTHELIAL-CELLS; IXODES-SCAPULARIS;
CEREBRAL MALARIA
AB Objective-The coagulation-inflammation cycle has been implicated as a critical component in malaria pathogenesis. Defibrotide (DF), a mixture of DNA aptamers, displays anticoagulant, anti-inflammatory, and endothelial cell (EC)-protective activities and has been successfully used to treat comatose children with veno-occlusive disease. DF was investigated here as a drug to treat cerebral malaria.
Methods and Results-DF blocks tissue factor expression by ECs incubated with parasitized red blood cells and attenuates prothrombinase activity, platelet aggregation, and complement activation. In contrast, it does not affect nitric oxide bioavailability. We also demonstrated that Plasmodium falciparum glycosylphosphatidylinositol (Pf-GPI) induces tissue factor expression in ECs and cytokine production by dendritic cells. Notably, dendritic cells, known to modulate coagulation and inflammation systemically, were identified as a novel target for DF. Accordingly, DF inhibits Toll-like receptor ligand-dependent dendritic cells activation by a mechanism that is blocked by adenosine receptor antagonist (8-p-sulfophenyltheophylline) but not reproduced by synthetic poly-A, -C, -T, and -G. These results imply that aptameric sequences and adenosine receptor mediate dendritic cells responses to the drug. DF also prevents rosetting formation, red blood cells invasion by P. falciparum and abolishes oocysts development in Anopheles gambiae. In a murine model of cerebral malaria, DF affected parasitemia, decreased IFN-gamma levels, and ameliorated clinical score (day 5) with a trend for increased survival.
Conclusion-Therapeutic use of DF in malaria is proposed. (Arterioscler Thromb Vasc Biol. 2012; 32:786-798.)
C1 [Francischetti, Ivo M. B.] NIAID, Sect Vector Biol, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA.
[Oliveira, Carlo J.] Univ Fed Triangulo Mineiro, Inst Ciencias Biol & Nat, Uberaba, Brazil.
[Yager, Stephanie B.; Lin, Christina K.; Vickers, Brandi K.; Waisberg, Michael] NIAID, Immunogenet Lab, NIH, Bethesda, MD 20892 USA.
[Debierre-Grockiego, Francoise; Schwarz, Ralph T.] Univ Marburg, Parasitol Lab, Inst Virol, Marburg, Germany.
[Debierre-Grockiego, Francoise] Parasite Immunol Vaccinol & Antiinfect Biotherapy, Tours, France.
[Carregaro, Vanessa] Univ Sao Paulo, Dept Farmacol, BR-14049 Ribeirao Preto, Brazil.
[Carregaro, Vanessa] Univ Sao Paulo, Dept Imunol, BR-14049 Ribeirao Preto, Brazil.
[Hume, Jen C. C.] Seattle Biomed Res Inst, Seattle, WA 98109 USA.
[Schwarz, Ralph T.] Univ Lille Nord France, Unit Struct & Funct Glycobiol, Lille, France.
[Seydel, Karl B.] Michigan State Univ, Coll Osteopath Med, Dept Med, E Lansing, MI 48824 USA.
[Iacobelli, Massimo] Gentium SpA, Como, Italy.
[Wang, Xunde] NHLBI, Pulm & Vasc Med Branch, NIH, Bethesda, MD 20892 USA.
[Monteiro, Robson Q.] Univ Fed Rio de Janeiro, Inst Bioquim Med, Rio De Janeiro, Brazil.
[Kotsyfakis, Michail] Acad Sci Czech Republic, Inst Parasitol, Ctr Biol, CR-37005 Ceske Budejovice, Czech Republic.
[Sa-Nunes, Anderson] Univ Sao Paulo, Inst Ciencias Biomed, Dept Imunol, BR-05508 Sao Paulo, Brazil.
RP Francischetti, IMB (reprint author), NIAID, Sect Vector Biol, Lab Malaria & Vector Res, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM ifrancischetti@niaid.nih.gov
RI Carregaro, Vanessa/D-2913-2012; Sa-Nunes, Anderson/D-8667-2012; Inbeb,
Inct/K-2317-2013; Kotsyfakis, Michail/G-9525-2014; Monteiro,
Robson/B-8007-2014; Ribeiro, Jose/J-7011-2015;
OI Sa-Nunes, Anderson/0000-0002-1859-4973; Kotsyfakis,
Michail/0000-0002-7526-1876; Ribeiro, Jose/0000-0002-9107-0818
FU Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, National Institutes of Health; DFG, Bonn, Germany
[SCHW 296/18-2]; Brazilian Malaria Network
[MCT/CNPq/MS/SCTIE/DECIT/PRONEX 555648/2009-5]; National Academy of
Sciences of the Czech Republic [Z60220518]
FX This work was supported by the Intramural Research Program of the
Division of Intramural Research, National Institute of Allergy and
Infectious Diseases, National Institutes of Health. Ralph T. Schwarz
received a grant (SCHW 296/18-2) from DFG, Bonn, Germany. Anderson
Sa-Nunes is recipient of grant MCT/CNPq/MS/SCTIE/DECIT/PRONEX
555648/2009-5 from the Brazilian Malaria Network. Michail Kotsyfakis
received support from grant number Z60220518 and from a Jan Evangelista
Purkyne fellowship of the National Academy of Sciences of the Czech
Republic.
NR 58
TC 13
Z9 13
U1 1
U2 6
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 1079-5642
J9 ARTERIOSCL THROM VAS
JI Arterioscler. Thromb. Vasc. Biol.
PD MAR
PY 2012
VL 32
IS 3
BP 786
EP U575
DI 10.1161/ATVBAHA.111.240291
PG 30
WC Hematology; Peripheral Vascular Disease
SC Hematology; Cardiovascular System & Cardiology
GA 897HP
UT WOS:000300639300035
PM 22116094
ER
PT J
AU Scuteri, A
Orru', M
Morrell, CH
Tarasov, K
Schlessinger, D
Uda, M
Lakatta, EG
AF Scuteri, Angelo
Orru', Marco
Morrell, Christopher H.
Tarasov, Kirill
Schlessinger, David
Uda, Manuela
Lakatta, Edward G.
TI Associations of large artery structure and function with adiposity:
Effects of age, gender, and hypertension. The SardiNIA Study
SO ATHEROSCLEROSIS
LA English
DT Article
DE Arteries; Arterial stiffness; Carotid intima-media thickness; Obesity;
Waist circumference; Population study
ID BODY-MASS-INDEX; INTIMA-MEDIA THICKNESS; PULSE-WAVE VELOCITY; METABOLIC
SYNDROME; CARDIOVASCULAR-DISEASE; ABDOMINAL ADIPOSITY; CAROTID-ARTERY;
RISK-FACTOR; MYOCARDIAL-INFARCTION; INDEPENDENT PREDICTOR
AB In the context of obesity epidemic, no large population study has extensively investigated the relationships between total and abdominal adiposity and large artery structure and function nor have such relationships been examined by gender, by age, by hypertensive status. We investigated these potential relationships in a large cohort of community dwelling volunteers participating the SardiNIA Study.
Methods and results: Total and visceral adiposity and arterial properties were assessed in 6148 subjects, aged 14-102 in a cluster of 4 towns in Sardinia, Italy. Arterial stiffness was measured as aortic pulse wave velocity (PWV), arterial thickness and lumen as common carotid artery (CCA) intima-media thickness (IMT) and diameter, respectively. We reported a nonlinear relationship between total and visceral adiposity and arterial stiffness, thickness, and diameter. The association between adiposity and arterial properties was steeper in women than in men, in younger than in older subjects. Waist correlated with arterial properties better than BMI. Within each BMI quartile, increasing waist circumference was associated with further significant changes in arterial structure and function.
Conclusion: The relationship between total or abdominal adiposity and arterial aging (PWV and CCA IMT) is not linear as described in the current study. Therefore, BMI- and/or waist-specific reference values for arterial measurements might need to be defined. Published by Elsevier Ireland Ltd.
C1 [Scuteri, Angelo; Morrell, Christopher H.; Tarasov, Kirill; Lakatta, Edward G.] NIA, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA.
[Orru', Marco; Uda, Manuela] Cittadella Univ Monserrato, CNR, INN, I-09042 Cagliari, Italy.
[Schlessinger, David] NIA, Genet Lab, NIH, Baltimore, MD 21224 USA.
[Morrell, Christopher H.] Loyola Univ Maryland, Baltimore, MD USA.
RP Scuteri, A (reprint author), INRCA IRCCS, UOC Geriatria, Via Cassia 1167, I-00189 Rome, Italy.
EM angeloelefante@interfree.it
FU NIA [NO1-AG-1-2109]; NIH, National Institute on Aging (USA)
FX The SardiNIA team was supported by Contract NO1-AG-1-2109 from the NIA.;
This research was supported in part by the Intramural Research Program
of the NIH, National Institute on Aging (USA).
NR 51
TC 26
Z9 27
U1 0
U2 2
PU ELSEVIER IRELAND LTD
PI CLARE
PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000,
IRELAND
SN 0021-9150
J9 ATHEROSCLEROSIS
JI Atherosclerosis
PD MAR
PY 2012
VL 221
IS 1
BP 189
EP 197
DI 10.1016/j.atherosclerosis.2011.11.045
PG 9
WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease
SC Cardiovascular System & Cardiology
GA 897EV
UT WOS:000300629500028
PM 22222417
ER
PT J
AU Veeraragavan, S
Graham, D
Bui, N
Yuva-Paylor, LA
Wess, J
Paylor, R
AF Veeraragavan, Surabi
Graham, Deanna
Bui, Nghiem
Yuva-Paylor, Lisa A.
Wess, Juergen
Paylor, Richard
TI Genetic reduction of muscarinic M-4 receptor modulates analgesic
response and acoustic startle response in a mouse model of fragile X
syndrome (FXS)
SO BEHAVIOURAL BRAIN RESEARCH
LA English
DT Article
DE Fragile X syndrome; Muscarinic; M-4 receptors; Analgesic response;
Behavior; Sensorimotor gating
ID FMR1 KNOCKOUT MICE; SENSORIMOTOR GATING ABNORMALITIES; SERTOLI-CELL
PROLIFERATION; BEHAVIORAL-TEST BATTERIES; SELF-INJURIOUS-BEHAVIOR;
ACETYLCHOLINE-RECEPTOR; MENTAL-RETARDATION; PREPULSE INHIBITION;
TEGMENTAL NUCLEUS; M4
AB Introduction: The G-protein coupled muscarinic acetylcholine receptors, widely expressed in the CNS, have been implicated in fragile X syndrome (FXS). Recent studies have reported an overactive signaling through the muscarinic receptors in the Fmr1KO mouse model. Hence, it was hypothesized that reducing muscarinic signaling might modulate behavioral phenotypes in the Fmr1KO mice. Pharmacological studies from our lab have provided evidence for this hypothesis, with subtype-preferring muscarinic M-1 and M-4 receptor antagonists modulating select behaviors in the Fmr1KO mice. Since the pharmacological antagonists were not highly specific, we investigated the specific role of M-4 receptors in the Fmr1KO mouse model, using a genetic approach.
Methods: We created a double mutant heterozygous for the M-4 receptor gene and hemizygous for the Fmr1 gene and examined the mutants on various behaviors. Each animal was tested on a behavior battery comprising of open-field activity (activity), light-dark (anxiety), marble burying (perseverative behavior), prepulse inhibition (sensorimotor gating), rotarod (motor coordination), passive avoidance (learning and memory) and hotplate (analgesia). Animals were also tested on the audiogenic seizure protocol and testis weights were measured.
Results: Reduction of M-4 receptor expression in the heterozygotes completely rescued the analgesic response and partly rescued the acoustic startle response phenotype in the Fmr1KO mice. However, no modulation was observed in a number of behaviors including learning and memory, activity, perseverative behavior and audiogenic seizures.
Conclusion: Reducing M-4 receptor signaling altered only select behavioral phenotypes in the Fmr1KO mouse model, suggesting that other targets are involved in the modulation of fragile X behaviors. (C) 2011 Elsevier B.V. All rights reserved.
C1 [Veeraragavan, Surabi; Graham, Deanna; Bui, Nghiem; Yuva-Paylor, Lisa A.; Paylor, Richard] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA.
[Paylor, Richard] Baylor Coll Med, Dept Neurosci, Houston, TX 77030 USA.
[Wess, Juergen] NIDDK, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA.
RP Paylor, R (reprint author), Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA.
EM veerarag@bcm.edu; deannag@bcm.edu; nbui@bcm.edu; lisay@bcm.edu;
jwess@helix.nih.gov; rpaylor@bcm.edu
FU Baylor Fragile X Center; Baylor College of Medicine Intellectual and
Developmental Disabilities Research Center
FX This research was supported by the Baylor Fragile X Center and the
Baylor College of Medicine Intellectual and Developmental Disabilities
Research Center
NR 59
TC 20
Z9 21
U1 0
U2 2
PU ELSEVIER SCIENCE BV
PI AMSTERDAM
PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS
SN 0166-4328
J9 BEHAV BRAIN RES
JI Behav. Brain Res.
PD MAR 1
PY 2012
VL 228
IS 1
BP 1
EP 8
DI 10.1016/j.bbr.2011.11.018
PG 8
WC Behavioral Sciences; Neurosciences
SC Behavioral Sciences; Neurosciences & Neurology
GA 895CA
UT WOS:000300472600001
PM 22123412
ER
PT J
AU Zhou, ZL
Yu, PP
Geller, HM
Ober, CK
AF Zhou, Zhaoli
Yu, Panpan
Geller, Herbert M.
Ober, Christopher K.
TI The role of hydrogels with tethered acetylcholine functionality on the
adhesion and viability of hippocampal neurons and glial cells
SO BIOMATERIALS
LA English
DT Article
DE PEG-based hydrogels; Neurotransmitters; Acetylcholine functionality;
Concentration-dependent manner
ID MEMBRANE-RECEPTORS; NEURITE OUTGROWTH; STEM-CELLS; POLYMER;
DIFFERENTIATION; REGENERATION; ATTACHMENT; BEHAVIOR; SCAFFOLD; MODULUS
AB In neural tissue engineering, designing materials with the right chemical cues is crucial in providing a permissive microenvironment to encourage and guide neuronal cell attachment and differentiation. Modifying synthetic hydrogels with biologically active molecules has become an increasingly important route in this field to provide a successful biomaterial and cell interaction. This study presents a strategy of using the monomer 2-methacryloxyethyl trimethylammonium chloride (MAETAC) to provide tethered neurotransmitter acetylcholine-like functionality with a complete 2-acetoxy-N,N,N-trimethylethanaminium segment, thereby modifying the properties of commonly used, non-adhesive PEG-based hydrogels. The effect of the functional monomer concentration on the physical properties of the hydrogels was systematically studied, and the resulting hydrogels were also evaluated for mice hippocampal neural cell attachment and growth. Results from this study showed that MAETAC in the hydrogels promotes neuronal cell attachment and differentiation in a concentration-dependent manner, different proportions of MAETAC monomer in the reaction mixture produce hydrogels with different porous structures, swollen states, and mechanical strengths. Growth of mice hippocampal cells cultured on the hydrogels showed differences in number, length of processes and exhibited different survival rates. Our results indicate that chemical composition of the biomaterials is a key factor in neural cell attachment and growth, and integration of the appropriate amount of tethered neurotransmitter functionalities can be a simple and effective way to optimize existing biomaterials for neuronal tissue engineering applications. (C) 2011 Elsevier Ltd. All rights reserved.
C1 [Zhou, Zhaoli; Ober, Christopher K.] Cornell Univ, Dept Mat Sci & Engn, Ithaca, NY 14853 USA.
[Zhou, Zhaoli; Ober, Christopher K.] Cornell Univ, Dept Chem & Chem Biol, Ithaca, NY 14853 USA.
[Yu, Panpan; Geller, Herbert M.] NHLBI, Dev Neurobiol Sect, Div Intramural Res, NIH, Bethesda, MD 20892 USA.
RP Ober, CK (reprint author), Cornell Univ, Dept Mat Sci & Engn, Ithaca, NY 14853 USA.
EM cko3@cornell.edu
RI Yu, Panpan/A-4962-2013;
OI Geller, Herbert/0000-0002-7048-6144
FU National Science Foundation Materials Research Science and Engineering
Center [DMR-0520404]; NIH [NSR01-044287]; Nanobiotechnology Centre
(NBTC); STC of the National Science Foundation [ECS-9876771]; NHLBI
Division of Intramural Research
FX We would like to acknowledge Dr. Ray Molloy and Professor Manfred Lindau
for the initial cell studies. We would also like to acknowledge the use
of the Microscopy and Imaging Facility at Cornell University and its
facility manager, Carol Bayles, and the use of the electron microscope
and the dynamic mechanical analyzer housed in the Cornell Center for
Materials Research (CCMR), Shared Experimental Facilities, supported
through the National Science Foundation Materials Research Science and
Engineering Center Program (DMR-0520404) and the facility managers, John
Hunt and Yuanming Zhang. We also acknowledge the assistance of the NHLBI
DIR Light Microscopy Core Facility. This work was partially supported by
NIH NSR01-044287 and by the Nanobiotechnology Centre (NBTC), an STC
program of the National Science Foundation under agreement no.
ECS-9876771, as well as the NHLBI Division of Intramural Research (P.Y.
and H.M.G).
NR 37
TC 14
Z9 14
U1 1
U2 17
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 MAR
PY 2012
VL 33
IS 8
BP 2473
EP 2481
DI 10.1016/j.biomaterials.2011.12.005
PG 9
WC Engineering, Biomedical; Materials Science, Biomaterials
SC Engineering; Materials Science
GA 895AY
UT WOS:000300469800007
PM 22196899
ER
PT J
AU Huang, CY
Qin, J
Follmann, DA
AF Huang, Chiung-Yu
Qin, Jing
Follmann, Dean A.
TI A maximum pseudo-profile likelihood estimator for the Cox model under
length-biased sampling
SO BIOMETRIKA
LA English
DT Article
DE Approximate likelihood; Cross-sectional sampling; Product-limit
estimator; Random truncation; Screening trials
ID REGRESSION-MODELS; SURVIVAL-DATA; DURATION; UNEMPLOYMENT; TIMES; AIDS
AB This paper considers semiparametric estimation of the Cox proportional hazards model for right-censored and length-biased data arising from prevalent sampling. To exploit the special structure of length-biased sampling, we propose a maximum pseudo-profile likelihood estimator, which can handle time-dependent covariates and is consistent under covariate-dependent censoring. Simulation studies show that the proposed estimator is more efficient than its competitors. A data analysis illustrates the methods and theory.
C1 [Huang, Chiung-Yu; Qin, Jing; Follmann, Dean A.] NIAID, Biostatist Res Branch, NIH, Bethesda, MD 20892 USA.
RP Huang, CY (reprint author), NIAID, Biostatist Res Branch, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM huangchi@niaid.nih.gov; jingqin@niaid.nih.gov; dfollmann@niaid.nih.gov
FU National Health Research and Development Program, Canada; Pfizer Canada
Incorporated through the Medical Research Council/Pharmaceutical
Manufacturers Association of Canada; Bayer Incorporated; British
Columbia Health Research Foundation
FX The authors thank Professors Ian McDowell, Masoud Asgharian and
Christina Wolfson for kindly sharing the Canadian Study of Health and
Aging data. The core study was funded by the National Health Research
and Development Program, Canada. Additional funding was provided by
Pfizer Canada Incorporated through the Medical Research
Council/Pharmaceutical Manufacturers Association of Canada Health
Activity Program, Bayer Incorporated and the British Columbia Health
Research Foundation. The authors also thank the referees, associate
editor and editor for their comments which improved the presentation of
this article.
NR 22
TC 10
Z9 10
U1 0
U2 9
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0006-3444
J9 BIOMETRIKA
JI Biometrika
PD MAR
PY 2012
VL 99
IS 1
BP 199
EP 210
DI 10.1093/biomet/asr072
PG 12
WC Biology; Mathematical & Computational Biology; Statistics & Probability
SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational
Biology; Mathematics
GA 898IC
UT WOS:000300734400015
ER
PT J
AU Liu, AY
Liu, CL
Zhang, ZW
Albert, PS
AF Liu, Aiyi
Liu, Chunling
Zhang, Zhiwei
Albert, Paul S.
TI Optimality of group testing in the presence of misclassification
SO BIOMETRIKA
LA English
DT Article
DE Binary outcome; Maximum likelihood estimation; Pooling; Prevalence;
Sensitivity; Specificity
ID ESTIMATING PREVALENCE; RARE DISEASE; TEST ERROR; PROPORTIONS; HIV;
SPECIFICITY; SENSITIVITY; ANTIBODIES; SERA
AB Several optimality properties of Dorfman's (1943) group testing procedure are derived for estimation of the prevalence of a rare disease whose status is classified with error. Exact ranges of disease prevalence are obtained for which group testing provides more efficient estimation when group size increases.
C1 [Liu, Aiyi; Zhang, Zhiwei; Albert, Paul S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biostat & Bioinformat Branch, Rockville, MD 20852 USA.
[Liu, Chunling] Hong Kong Polytech Univ, Dept Appl Math, Hong Kong, Hong Kong, Peoples R China.
RP Liu, AY (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Biostat & Bioinformat Branch, Rockville, MD 20852 USA.
EM liua@mail.nih.gov; Catherine.Chunling.Liu@inet.polyu.edu.hk;
zhangz7@mail.nih.gov; albertp@mail.nih.gov
RI Ghartouchent, malek/B-9088-2012; Liu, Chunling/A-4827-2015;
OI Liu, Chunling/0000-0003-3410-445X; Liu, Aiyi/0000-0002-6618-5082
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development of the National Institutes of Health
FX This research was supported by the Intramural Research Program of the
Eunice Kennedy Shriver National Institute of Child Health and Human
Development of the National Institutes of Health. The authors thank the
editor, associate editor and two referees for their constructive
comments, and Dr Yaakov Malinovsky for helpful discussions.
NR 28
TC 11
Z9 11
U1 1
U2 3
PU OXFORD UNIV PRESS
PI OXFORD
PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND
SN 0006-3444
EI 1464-3510
J9 BIOMETRIKA
JI Biometrika
PD MAR
PY 2012
VL 99
IS 1
BP 245
EP 251
DI 10.1093/biomet/asr064
PG 7
WC Biology; Mathematical & Computational Biology; Statistics & Probability
SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational
Biology; Mathematics
GA 898IC
UT WOS:000300734400020
ER
PT J
AU Kim, YS
Kumar, V
Lee, S
Iwai, A
Neckers, L
Malhotra, SV
Trepel, JB
AF Kim, Yeong Sang
Kumar, Vineet
Lee, Sunmin
Iwai, Aki
Neckers, Len
Malhotra, Sanjay V.
Trepel, Jane B.
TI Methoxychalcone inhibitors of androgen receptor translocation and
function
SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
LA English
DT Article
DE Chalcone; Antiandrogen; Androgen receptor translocation; Prostate
cancer; Hsp90
ID RESISTANT PROSTATE-CANCER; CHALCONES; THERAPIES
AB Androgen receptor activity drives incurable castrate-resistant prostate cancer. All approved antiandrogens inhibit androgen receptor-driven transcription, and in addition the second-generation antiandrogen MDV3100 inhibits ligand-activated androgen receptor nuclear translocation, via an unknown mechanism. Here, we report methoxychalcones that lock the heat shock protein 90-androgen receptor complex in the cytoplasm in an androgen-non-responsive state, thus demonstrating a novel chemical scaffold for antiandrogen development and a unique mechanism of antiandrogen activity. Published by Elsevier Ltd.
C1 [Kumar, Vineet; Malhotra, Sanjay V.] Natl Canc Inst Frederick, Lab Synthet Chem, Dev Therapeut Program Support, SAIC Frederick, Frederick, MD 21702 USA.
[Kim, Yeong Sang; Lee, Sunmin; Trepel, Jane B.] NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA.
[Iwai, Aki; Neckers, Len] NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA.
RP Malhotra, SV (reprint author), Natl Canc Inst Frederick, Lab Synthet Chem, Dev Therapeut Program Support, SAIC Frederick, 1050 Boyles St, Frederick, MD 21702 USA.
EM malhotrasa@mail.nih.gov; trepelj@mail.nih.gov
FU NCI, National Institutes of Health; DTP NCI-Frederick SAIC
[HSN261200800001E]
FX V.K. and S. V. M. would like to thank the National Cancer Institute
(NCI) Developmental Therapeutics Program. This project has been funded
in whole or in part with federal funds from the NCI, National Institutes
of Health, to the Intramural Research Program (Y.S.K., A. I., S. L.,
L.N., and J.B.T.), and to DTP NCI-Frederick SAIC, under Contract No.
HSN261200800001E. The content of this publication does not necessarily
reflect the views or policies of the Department of Health and Human
Services, nor does mention of trade names, commercial products, or
organizations imply endorsement by the U.S. Government.
NR 25
TC 7
Z9 7
U1 0
U2 6
PU PERGAMON-ELSEVIER SCIENCE LTD
PI OXFORD
PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND
SN 0960-894X
J9 BIOORG MED CHEM LETT
JI Bioorg. Med. Chem. Lett.
PD MAR 1
PY 2012
VL 22
IS 5
BP 2105
EP 2109
DI 10.1016/j.bmcl.2011.12.141
PG 5
WC Chemistry, Medicinal; Chemistry, Organic
SC Pharmacology & Pharmacy; Chemistry
GA 894UA
UT WOS:000300451200053
PM 22310230
ER
PT J
AU Yu, BB
Tiwari, RC
AF Yu, Binbing
Tiwari, Ram C.
TI A Bayesian approach to mixture cure models with spatial frailties for
population-based cancer relative survival data
SO CANADIAN JOURNAL OF STATISTICS-REVUE CANADIENNE DE STATISTIQUE
LA English
DT Article
DE Colon cancer; cure fraction; finite mixture models; random effects;
relative survival; SEER
ID FAILURE TIME MODEL; REGRESSION-MODELS; FRACTION; CHILDHOOD; DEATHS
AB As the treatments of cancer progress, a certain number of cancers are curable if diagnosed early. In population-based cancer survival studies, cure is said to occur when mortality rate of the cancer patients returns to the same level as that expected for the general cancer-free population. The estimates of cure fraction are of interest to both cancer patients and health policy makers. Mixture cure models have been widely used because the model is easy to interpret by separating the patients into two distinct groups. Usually parametric models are assumed for the latent distribution for the uncured patients. The estimation of cure fraction from the mixture cure model may be sensitive to misspecification of latent distribution. We propose a Bayesian approach to mixture cure model for population-based cancer survival data, which can be extended to county-level cancer survival data. Instead of modeling the latent distribution by a fixed parametric distribution, we use a finite mixture of the union of the lognormal, loglogistic, and Weibull distributions. The parameters are estimated using the Markov chain Monte Carlo method. Simulation study shows that the Bayesian method using a finite mixture latent distribution provides robust inference of parameter estimates. The proposed Bayesian method is applied to relative survival data for colon cancer patients from the Surveillance, Epidemiology, and End Results (SEER) Program to estimate the cure fractions. The Canadian Journal of Statistics 40: 4054; 2012 (C) 2012 Statistical Society of Canada
C1 [Yu, Binbing] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
[Tiwari, Ram C.] US FDA, Off Biostat, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA.
RP Yu, BB (reprint author), NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA.
EM yubi@mail.nih.gov
FU National Institute on Aging, National Institutes of Health
FX The authors wish to thank two anonymous reviewers and the Associate
Editor for their helpful comments. The views expressed in this article
by the author, Dr. Tiwari, are solely his own and do necessarily reflect
that of the FDA. Dr. Yu was supported in part by the Intramural Research
Program of the National Institute on Aging, National Institutes of
Health. This research utilised the high-performance computational
capabilities of the Biowulf PC/Linux cluster at the National Institutes
of Health, Bethesda, Maryland, USA (http://biowulf.nih.gov).
NR 36
TC 3
Z9 3
U1 0
U2 8
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0319-5724
J9 CAN J STAT
JI Can. J. Stat.-Rev. Can. Stat.
PD MAR
PY 2012
VL 40
IS 1
BP 40
EP 54
DI 10.1002/cjs.10135
PG 15
WC Statistics & Probability
SC Mathematics
GA 897PY
UT WOS:000300667000003
ER
PT J
AU Rahma, OE
Ashtar, E
Czystowska, M
Szajnik, ME
Wieckowski, E
Bernstein, S
Herrin, VE
Shams, MA
Steinberg, SM
Merino, M
Gooding, W
Visus, C
DeLeo, AB
Wolf, JK
Bell, JG
Berzofsky, JA
Whiteside, TL
Khleif, SN
AF Rahma, Osama E.
Ashtar, Ed
Czystowska, Malgorzata
Szajnik, Marta E.
Wieckowski, Eva
Bernstein, Sarah
Herrin, Vincent E.
Shams, Mortada A.
Steinberg, Seth M.
Merino, Maria
Gooding, William
Visus, Carmen
DeLeo, Albert B.
Wolf, Judith K.
Bell, Jeffrey G.
Berzofsky, Jay A.
Whiteside, Theresa L.
Khleif, Samir N.
TI A gynecologic oncology group phase II trial of two p53 peptide vaccine
approaches: subcutaneous injection and intravenous pulsed dendritic
cells in high recurrence risk ovarian cancer patients
SO CANCER IMMUNOLOGY IMMUNOTHERAPY
LA English
DT Article
DE p53; IL-2; Ovarian cancer; Cancer vaccine
ID COLONY-STIMULATING FACTOR; REGULATORY T-CELLS; ANTITUMOR
IMMUNE-RESPONSES; METASTATIC RENAL-CANCER; ADVANCED BREAST-CANCER;
MELANOMA PATIENTS; INTRANODAL INJECTION; ANTIGEN PRESENTATION; CTL
RESPONSES; IMMUNIZATION
AB Peptide antigens have been administered by different approaches as cancer vaccine therapy, including direct injection or pulsed onto dendritic cells; however, the optimal delivery method is still debatable. In this study, we describe the immune response elicited by two vaccine approaches using the wild-type (wt) p53 vaccine.
Twenty-one HLA-A2.1 patients with stage III, IV, or recurrent ovarian cancer overexpressing the p53 protein with no evidence of disease were treated in two cohorts. Arm A received SC wt p53:264-272 peptide admixed with Montanide and GM-CSF. Arm B received wt p53:264-272 peptide-pulsed dendritic cells IV. Interleukin-2 (IL-2) was administered to both cohorts in alternative cycles.
Nine of 13 patients (69%) in arm A and 5 of 6 patients (83%) in arm B developed an immunologic response as determined by ELISPOT and tetramer assays. The vaccine caused no serious systemic side effects. IL-2 administration resulted in grade 3 and 4 toxicities in both arms and directly induced the expansion of T regulatory cells. The median overall survival was 40.8 and 29.6 months for arm A and B, respectively; the median progression-free survival was 4.2 and. 8.7 months, respectively.
We found that using either vaccination approach generates comparable specific immune responses against the p53 peptide with minimal toxicity. Accordingly, our findings suggest that the use of less demanding SC approach may be as effective. Furthermore, the use of low-dose SC IL-2 as an adjuvant might have interfered with the immune response. Therefore, it may not be needed in future trials.
C1 [Rahma, Osama E.; Ashtar, Ed; Bernstein, Sarah; Shams, Mortada A.; Berzofsky, Jay A.; Khleif, Samir N.] NCI, Vaccine Branch, CCR, Bethesda, MD 20892 USA.
[Czystowska, Malgorzata; Szajnik, Marta E.; Wieckowski, Eva; Gooding, William; Visus, Carmen; DeLeo, Albert B.; Whiteside, Theresa L.] Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA.
[Szajnik, Marta E.] Univ Med Sci, Dept Gynecol Oncol, PL-61107 Poznan, Poland.
[Herrin, Vincent E.] Univ Mississippi, Jackson, MS 39216 USA.
[Steinberg, Seth M.] NCI, Biostat & Data Management Sect, CCR, Rockville, MD USA.
[Merino, Maria] NIH, Ctr Clin, Dept Pathol, Bethesda, MD 20892 USA.
[Wolf, Judith K.] Univ Texas MD Anderson Canc Ctr, Dept GYN Oncol, Houston, TX 77030 USA.
[Bell, Jeffrey G.] Riverside Methodist Hosp, Columbus Canc Council, Div Gynecol Oncol, Columbus, OH 43214 USA.
RP Khleif, SN (reprint author), NCI, Vaccine Branch, CCR, 41 Medlars Dr,Bldg 41,Room B624, Bethesda, MD 20892 USA.
EM khleif@nih.gov
FU National Institute of Health (NIH), National Cancer Institute, Center
for Cancer Research; NCI/NIH [P01 CA109688, R01 DE13918]; National
Institute [CA27469, CA37517]; NHLBI [HB-37-165]
FX Supported in part by the intramural research program of the National
Institute of Health (NIH), National Cancer Institute, Center for Cancer
Research and by of the NCI/NIH grants P01 CA109688 (TLW) and R01 DE13918
(TLW) as well as National Institute grants to the Gynecologic Oncology
Group Administrative Office (CA27469) and the Gynecologic Oncology Group
Statistical Office (CA37517). Dr. M. Szajnik is a postdoctoral fellow
supported by the NHLBI contract HB-37-165 (TLW). The following member
institutions participated in this study: Tacoma General Hospital; MD
Anderson Cancer Center; Columbus Cancer Council and the Cleveland Clinic
Foundation.
NR 47
TC 42
Z9 45
U1 0
U2 5
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 0340-7004
J9 CANCER IMMUNOL IMMUN
JI Cancer Immunol. Immunother.
PD MAR
PY 2012
VL 61
IS 3
BP 373
EP 384
DI 10.1007/s00262-011-1100-9
PG 12
WC Oncology; Immunology
SC Oncology; Immunology
GA 897OC
UT WOS:000300659900008
PM 21927947
ER
PT J
AU Tejeda, HA
Shippenberg, TS
Henriksson, R
AF Tejeda, H. A.
Shippenberg, T. S.
Henriksson, R.
TI The dynorphin/kappa-opioid receptor system and its role in psychiatric
disorders
SO CELLULAR AND MOLECULAR LIFE SCIENCES
LA English
DT Review
DE Dynorphin; kappa-Opioid receptor; Psychiatric disorder; Pharmacology;
Neuroanatomy
ID MESSENGER-RNA EXPRESSION; CENTRAL-NERVOUS-SYSTEM; RAT NUCLEUS-ACCUMBENS;
PRODYNORPHIN GENE-EXPRESSION; CONDITIONED PLACE-PREFERENCE;
ELEMENT-BINDING PROTEIN; VENTRAL TEGMENTAL AREA; IN-VIVO MICRODIALYSIS;
SPRAGUE-DAWLEY RATS; AMINO-ACID-SEQUENCE
AB The dynorphin/kappa-opioid receptor system has been implicated in the pathogenesis and pathophysiology of several psychiatric disorders. In the present review, we present evidence indicating a key role for this system in modulating neurotransmission in brain circuits that subserve mood, motivation, and cognitive function. We overview the pharmacology, signaling, post-translational, post-transcriptional, transcriptional, epigenetic and cis regulation of the dynorphin/kappa-opioid receptor system, and critically review functional neuroanatomical, neurochemical, and pharmacological evidence, suggesting that alterations in this system may contribute to affective disorders, drug addiction, and schizophrenia. We also overview the dynorphin/kappa-opioid receptor system in the genetics of psychiatric disorders and discuss implications of the reviewed material for therapeutics development.
C1 [Tejeda, H. A.; Shippenberg, T. S.; Henriksson, R.] NIDA, Integrat Neurosci Sect, Integrat Neurosci Res Branch, IRP,NIH, Baltimore, MD 21224 USA.
[Tejeda, H. A.] Univ Maryland, Dept Anat & Neurobiol, Baltimore, MD 21201 USA.
[Henriksson, R.] Karolinska Inst, Dept Clin Neurosci, S-17176 Stockholm, Sweden.
RP Shippenberg, TS (reprint author), NIDA, Integrat Neurosci Sect, Integrat Neurosci Res Branch, IRP,NIH, 333 Cassell Dr, Baltimore, MD 21224 USA.
EM tshippen@intra.nida.nih.gov
FU National Institute on Drug Abuse; National Institute of Mental Health
[R01MH083928]; National Science Foundation; Ford Foundation; Meyerhoff
Fellowship; Department of Clinical Neuroscience, Karolinska Institutet
FX This review was supported by the: (1) Intramural Research Program,
National Institute on Drug Abuse; (2) National Institute of Mental
Health (R01MH083928); (3) National Science Foundation Graduate Research
Fellowship (HAT); (4) Ford Foundation Predoctoral Fellowship (HAT); (5)
Meyerhoff Fellowship (HAT); and (6) Department of Clinical Neuroscience,
Karolinska Institutet(RH). Special thanks to Dr. Vladimir Chefer for his
thoughtful comments on the manuscript.
NR 467
TC 52
Z9 54
U1 4
U2 23
PU SPRINGER BASEL AG
PI BASEL
PA PICASSOPLATZ 4, BASEL, 4052, SWITZERLAND
SN 1420-682X
J9 CELL MOL LIFE SCI
JI Cell. Mol. Life Sci.
PD MAR
PY 2012
VL 69
IS 6
BP 857
EP 896
DI 10.1007/s00018-011-0844-x
PG 40
WC Biochemistry & Molecular Biology; Cell Biology
SC Biochemistry & Molecular Biology; Cell Biology
GA 898IY
UT WOS:000300737200002
PM 22002579
ER
PT J
AU Lee, HK
Park, DW
Bae, JH
Kim, HJ
Shin, DG
Park, JS
Lee, JG
Lee, SJ
Bae, YS
Baek, SH
AF Lee, Hyung-Kyoung
Park, Dae-Weon
Bae, Jun Ho
Kim, Hyung Jun
Shin, Dong-Gu
Park, Jong-Seon
Lee, Jin-Gu
Lee, Sung Joong
Bae, Yoe-Sik
Baek, Suk-Hwan
TI RGS2 is a negative regulator of STAT3-mediated Nox1 expression
SO CELLULAR SIGNALLING
LA English
DT Article
DE RGS2; STAT3; PLD2; PKC-eta; Nox1
ID OXIDASE 1 EXPRESSION; FOAM CELL-FORMATION; TOLL-LIKE RECEPTORS;
BLOOD-PRESSURE; ANGIOTENSIN-II; HYPERTENSIVE PATIENTS; NADPH OXIDASES;
PROTEINS; LIPOPOLYSACCHARIDE; INFECTION
AB NADPH oxidase 1 (Nox1) is essential for reactive oxygen species production in the innate immune responses mediated by toll-like receptor (TLR), but the mechanism regulating its expression remains uncertain. Here, we find that Nox1 induction is TLR2-dependent, but independent of myeloid differentiation primary response gene 88 (MyD88). We demonstrate the capacity of signal transducer and activator of transcription 3 (STAT3) to activate Nox1's transcription, as well as cooperative regulation by Janus kinase 1 and 3 (JAK1 and JAK3). We find that regulator of G-protein signaling 2 (RGS2) inhibits STAT3-mediated Nox1 transcription, and can itself be repressed by TLR2; Nox1 induction upon RGS2 down-regulation is controlled by protein kinase C-eta (PKC-eta) and phospholipase D2 (PLD2). A GFP-tagged version of RGS2 concentrates in the nucleus; RGS2 additionally directly binds STAT3 to regulate its transcriptional activity through TLR2 stimulation. Cumulatively, these results suggest that TLR2 signaling enhances Nox1 expression through the JAK1/3-STAT3 pathway, and that RGS2, through its regulation by the PKC-eta/PLD2 pathway, represses STAT3's transcriptional activation of Nox1. (C) 2011 Published by Elsevier Inc.
C1 [Lee, Hyung-Kyoung; Park, Dae-Weon; Baek, Suk-Hwan] Yeungnam Univ, Dept Biochem & Mol Biol, Coll Med, Aging Associated Vasc Dis Res Ctr, Taegu 705802, South Korea.
[Bae, Jun Ho; Kim, Hyung Jun; Shin, Dong-Gu; Park, Jong-Seon] Yeungnam Univ, Coll Med, Dept Internal Med, Taegu 705802, South Korea.
[Lee, Jin-Gu] NIDDK, Dept Lab Mol Biol, NIH, Bethesda, MD USA.
[Lee, Sung Joong] Seoul Natl Univ, Sch Dent, Dept Neurosci, Dent Res Inst, Seoul, South Korea.
[Bae, Yoe-Sik] Sungkyunkwan Univ, Dept Biol Sci, Suwon, South Korea.
RP Baek, SH (reprint author), Yeungnam Univ, Dept Biochem & Mol Biol, Coll Med, Aging Associated Vasc Dis Res Ctr, 210 Main Bldg,317-1 Daemyung 5 Dong, Taegu 705802, South Korea.
EM sbaek@med.yu.ac.kr
FU Korean Science and Engineering Foundation (KOSEF); Korea government
(MEST) [2011-0006181]
FX This work was supported by the Korean Science and Engineering Foundation
(KOSEF) grant funded by the Korea government (MEST) (2011-0006181).
NR 39
TC 7
Z9 7
U1 1
U2 1
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 MAR
PY 2012
VL 24
IS 3
BP 803
EP 809
DI 10.1016/j.cellsig.2011.11.015
PG 7
WC Cell Biology
SC Cell Biology
GA 895EG
UT WOS:000300478400024
PM 22120521
ER
PT J
AU Fessler, MB
AF Fessler, M. B.
TI Next stop for HDL: the lung
SO CLINICAL AND EXPERIMENTAL ALLERGY
LA English
DT Editorial Material
ID ASTHMA; CHOLESTEROL; HYPERRESPONSIVENESS; LIPOPROTEINS; CHILDREN; CELLS
C1 Natl Inst Environm Hlth Sci, Lab Resp Biol, NIH, Res Triangle Pk, NC 27709 USA.
RP Fessler, MB (reprint author), Natl Inst Environm Hlth Sci, Lab Resp Biol, NIH, 111 TW Alexander Dr,POB 12233,MD D2-01, Res Triangle Pk, NC 27709 USA.
EM fesslerm@niehs.nih.gov
FU Intramural NIH HHS [ZIA ES102005-06]; NIEHS NIH HHS [Z01 ES102005]
NR 22
TC 4
Z9 4
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0954-7894
J9 CLIN EXP ALLERGY
JI Clin. Exp. Allergy
PD MAR
PY 2012
VL 42
IS 3
BP 340
EP 342
DI 10.1111/j.1365-2222.2011.03942.x
PG 3
WC Allergy; Immunology
SC Allergy; Immunology
GA 897TX
UT WOS:000300681600001
PM 22356140
ER
PT J
AU Baggott, MJ
Li, L
Galloway, GP
Scheidweiler, KB
Barnes, AJ
Huestis, MA
Mendelson, J
AF Baggott, M. J.
Li, L.
Galloway, G. P.
Scheidweiler, K. B.
Barnes, A. J.
Huestis, M. A.
Mendelson, J.
TI PHARMACOKINETICS OF ORAL 3,4-METHYLENEDIOXYAMPHETAMINE IN HUMANS
SO CLINICAL PHARMACOLOGY & THERAPEUTICS
LA English
DT Meeting Abstract
CT 113th Annual Meeting of the
American-Society-for-Clinical-Pharmacology-and-Therapeutics (ASCPT)
CY MAR 14-17, 2012
CL Natl Harbor, MD
SP Amer Soc Clin Pharmacol & Therapeut (ASCPT)
C1 [Baggott, M. J.; Li, L.; Galloway, G. P.; Mendelson, J.] CPMCRI, San Francisco, CA USA.
[Scheidweiler, K. B.; Barnes, A. J.; Huestis, M. A.] NIDA Intramural, Clin Pharmacol & Therapeut Res Branch, Baltimore, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0009-9236
J9 CLIN PHARMACOL THER
JI Clin. Pharmacol. Ther.
PD MAR
PY 2012
VL 91
SU 1
BP S135
EP S135
PG 1
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 895VN
UT WOS:000300524900361
ER
PT J
AU Cheang, KI
Xu, X
Veenstra, TD
Nestler, JE
AF Cheang, K. I.
Xu, X.
Veenstra, T. D.
Nestler, J. E.
TI ESTRADIOL METABOLITES AND CHANGES IN INSULIN SENSITIVITY DURING ORAL
CONTRACEPTIVE USE
SO CLINICAL PHARMACOLOGY & THERAPEUTICS
LA English
DT Meeting Abstract
CT 113th Annual Meeting of the
American-Society-for-Clinical-Pharmacology-and-Therapeutics (ASCPT)
CY MAR 14-17, 2012
CL Natl Harbor, MD
SP Amer Soc Clin Pharmacol & Therapeut (ASCPT)
C1 [Cheang, K. I.; Nestler, J. E.] Virginia Commonwealth Univ, Richmond, VA USA.
[Xu, X.; Veenstra, T. D.] NCI, Frederick, MD 21701 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0009-9236
J9 CLIN PHARMACOL THER
JI Clin. Pharmacol. Ther.
PD MAR
PY 2012
VL 91
SU 1
BP S25
EP S25
PG 1
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 895VN
UT WOS:000300524900064
ER
PT J
AU Gong, SL
Tai, W
Tsunoda, SM
Greenberg, HE
Gorski, JC
Penzak, SR
Stoch, SA
Ma, JD
AF Gong, S. L.
Tai, W.
Tsunoda, S. M.
Greenberg, H. E.
Gorski, J. C.
Penzak, S. R.
Stoch, S. A.
Ma, J. D.
TI ORAL MIDAZOLAM (MDZ) PARTIAL AREA-UNDER CURVE (AUC) DOES NOT RELIABLY
PREDICT CYTOCHROME P450 (CYP) 3A BASELINE ACTIVITY IN HEALTHY SUBJECTS.
SO CLINICAL PHARMACOLOGY & THERAPEUTICS
LA English
DT Meeting Abstract
CT 113th Annual Meeting of the
American-Society-for-Clinical-Pharmacology-and-Therapeutics (ASCPT)
CY MAR 14-17, 2012
CL Natl Harbor, MD
SP Amer Soc Clin Pharmacol & Therapeut (ASCPT)
C1 [Gong, S. L.; Tai, W.; Tsunoda, S. M.; Ma, J. D.] UCSD, Skaggs Sch Pharm & Pharmaceut Sci, La Jolla, CA USA.
[Greenberg, H. E.] Thomas Jefferson Univ, Dept Pharmacol & Expt Therapeut, Philadelphia, PA 19107 USA.
[Gorski, J. C.] Mylan Pharmaceut, Morgantown, WV USA.
[Penzak, S. R.] NIH, Dept Pharm, Bethesda, MD 20892 USA.
[Stoch, S. A.] Merck, Rahway, NJ USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0009-9236
J9 CLIN PHARMACOL THER
JI Clin. Pharmacol. Ther.
PD MAR
PY 2012
VL 91
SU 1
BP S42
EP S43
PG 2
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 895VN
UT WOS:000300524900110
ER
PT J
AU Iyer, LV
Ramamoorthy, A
Furimsky, AM
Tang, L
Catz, P
Green, CE
Wainer, IW
AF Iyer, L. V.
Ramamoorthy, A.
Furimsky, A. M.
Tang, L.
Catz, P.
Green, C. E.
Wainer, I. W.
TI STEREOSELECTIVE CONJUGATION OF 4 '-METHOXYFENOTEROL STEREOISOMERS BY
SULFOTRANSFERASES.
SO CLINICAL PHARMACOLOGY & THERAPEUTICS
LA English
DT Meeting Abstract
CT 113th Annual Meeting of the
American-Society-for-Clinical-Pharmacology-and-Therapeutics (ASCPT)
CY MAR 14-17, 2012
CL Natl Harbor, MD
SP Amer Soc Clin Pharmacol & Therapeut (ASCPT)
C1 [Iyer, L. V.; Furimsky, A. M.; Tang, L.; Catz, P.; Green, C. E.] SRI Int, Menlo Pk, CA USA.
[Ramamoorthy, A.; Wainer, I. W.] NIA, Baltimore, MD 21224 USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0009-9236
J9 CLIN PHARMACOL THER
JI Clin. Pharmacol. Ther.
PD MAR
PY 2012
VL 91
SU 1
BP S19
EP S19
PG 1
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 895VN
UT WOS:000300524900049
ER
PT J
AU Moaddel, R
Rosenberg, A
Abdrakhmanova, G
Jozwiak, K
Ramamoorthy, A
Wainer, IW
AF Moaddel, R.
Rosenberg, A.
Abdrakhmanova, G.
Jozwiak, K.
Ramamoorthy, A.
Wainer, I. W.
TI KETAMINE AND METABOLITES SUBTYPE SELECTIVITY IN THE NICOTINIC RECEPTOR
FAMILY.
SO CLINICAL PHARMACOLOGY & THERAPEUTICS
LA English
DT Meeting Abstract
CT 113th Annual Meeting of the
American-Society-for-Clinical-Pharmacology-and-Therapeutics (ASCPT)
CY MAR 14-17, 2012
CL Natl Harbor, MD
SP Amer Soc Clin Pharmacol & Therapeut (ASCPT)
C1 [Moaddel, R.; Rosenberg, A.; Ramamoorthy, A.; Wainer, I. W.] NIA, NIH, Baltimore, MD 21224 USA.
[Abdrakhmanova, G.] Virginia Commonwealth Univ, Richmond, VA USA.
[Jozwiak, K.] Med Univ Lublin, Lublin, Poland.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0009-9236
J9 CLIN PHARMACOL THER
JI Clin. Pharmacol. Ther.
PD MAR
PY 2012
VL 91
SU 1
BP S15
EP S16
PG 2
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 895VN
UT WOS:000300524900038
ER
PT J
AU Momary, KM
Jann, M
Spratlin, V
Zhang, H
Turner, D
Penzak, S
Wright, A
VanDenBerg, C
AF Momary, K. M.
Jann, M.
Spratlin, V.
Zhang, H.
Turner, D.
Penzak, S.
Wright, A.
VanDenBerg, C.
TI LACK OF EFFECT OF ABCB1 GENOTYPE ON THE DRUG-DRUG INTERACTIONS BETWEEN
INDINAVIR AND VENLAFAXINE EXTENDED-RELEASE OR DESVENLAFAXINE
EXTENDED-RELEASE.
SO CLINICAL PHARMACOLOGY & THERAPEUTICS
LA English
DT Meeting Abstract
CT 113th Annual Meeting of the
American-Society-for-Clinical-Pharmacology-and-Therapeutics (ASCPT)
CY MAR 14-17, 2012
CL Natl Harbor, MD
SP Amer Soc Clin Pharmacol & Therapeut (ASCPT)
C1 [Momary, K. M.; Jann, M.; Spratlin, V.; Zhang, H.; Turner, D.; Wright, A.; VanDenBerg, C.] Mercer Univ, Coll Pharm & Hlth Sci, Atlanta, GA USA.
[Penzak, S.] NIH, Clin Pharmacokinet Lab, Bethesda, MD 20892 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0009-9236
J9 CLIN PHARMACOL THER
JI Clin. Pharmacol. Ther.
PD MAR
PY 2012
VL 91
SU 1
BP S120
EP S121
PG 2
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 895VN
UT WOS:000300524900320
ER
PT J
AU Ramamoorthy, A
Van Wart, S
de Cabo, R
Mager, D
Wainer, I
AF Ramamoorthy, A.
Van Wart, S.
de Cabo, R.
Mager, D.
Wainer, I.
TI POPULATION PHARMACOKINETIC ANALYSIS OF (R)- AND (S)-KETAMINE AND
NORKETAMINE IN RATS ON AD LIB AND CALORIE RESTRICTED DIETS
SO CLINICAL PHARMACOLOGY & THERAPEUTICS
LA English
DT Meeting Abstract
CT 113th Annual Meeting of the
American-Society-for-Clinical-Pharmacology-and-Therapeutics (ASCPT)
CY MAR 14-17, 2012
CL Natl Harbor, MD
SP Amer Soc Clin Pharmacol & Therapeut (ASCPT)
C1 [Ramamoorthy, A.; de Cabo, R.; Wainer, I.] NIA, NIH, Baltimore, MD 21224 USA.
[Van Wart, S.; Mager, D.] SUNY Buffalo, Buffalo, NY 14260 USA.
RI de Cabo, Rafael/J-5230-2016
OI de Cabo, Rafael/0000-0002-3354-2442
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0009-9236
J9 CLIN PHARMACOL THER
JI Clin. Pharmacol. Ther.
PD MAR
PY 2012
VL 91
SU 1
BP S26
EP S27
PG 2
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 895VN
UT WOS:000300524900068
ER
PT J
AU Sanghvi, M
Moaddel, R
OLoughlin, K
Green, C
Ramamoorthy, A
Wainer, I
AF Sanghvi, M.
Moaddel, R.
OLoughlin, K.
Green, C.
Ramamoorthy, A.
Wainer, I.
TI DETERMINATION OF KETAMINE AND ITS DOWNSTREAM METABOLITES IN PLASMA AND
BRAIN OF WISTAR RATS
SO CLINICAL PHARMACOLOGY & THERAPEUTICS
LA English
DT Meeting Abstract
CT 113th Annual Meeting of the
American-Society-for-Clinical-Pharmacology-and-Therapeutics (ASCPT)
CY MAR 14-17, 2012
CL Natl Harbor, MD
SP Amer Soc Clin Pharmacol & Therapeut (ASCPT)
C1 [Sanghvi, M.; Moaddel, R.; Ramamoorthy, A.; Wainer, I.] NIA, NIH, Baltimore, MD 21224 USA.
[OLoughlin, K.; Green, C.] SRI Int, Menlo Pk, CA 94025 USA.
NR 0
TC 0
Z9 0
U1 0
U2 1
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0009-9236
J9 CLIN PHARMACOL THER
JI Clin. Pharmacol. Ther.
PD MAR
PY 2012
VL 91
SU 1
BP S27
EP S27
PG 1
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 895VN
UT WOS:000300524900069
ER
PT J
AU Singh, NS
Paul, RK
Sichler, M
Moaddel, R
Bernier, M
Wainer, IW
Ramamoorthy, A
AF Singh, N. S.
Paul, R. K.
Sichler, M.
Moaddel, R.
Bernier, M.
Wainer, I. W.
Ramamoorthy, A.
TI CAPILLARY ELECTROPHORESIS-LASER INDUCED FLUORESCENCE (CE-LIF) ASSAY FOR
MEASUREMENT OF INTRA-CELLULAR D-SERINE AND SERINE RACEMASE ACTIVITY.
SO CLINICAL PHARMACOLOGY & THERAPEUTICS
LA English
DT Meeting Abstract
CT 113th Annual Meeting of the
American-Society-for-Clinical-Pharmacology-and-Therapeutics (ASCPT)
CY MAR 14-17, 2012
CL Natl Harbor, MD
SP Amer Soc Clin Pharmacol & Therapeut (ASCPT)
C1 [Singh, N. S.; Paul, R. K.; Sichler, M.; Moaddel, R.; Bernier, M.; Wainer, I. W.; Ramamoorthy, A.] NIA, NIH, Baltimore, MD 21224 USA.
NR 0
TC 0
Z9 0
U1 0
U2 2
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0009-9236
J9 CLIN PHARMACOL THER
JI Clin. Pharmacol. Ther.
PD MAR
PY 2012
VL 91
SU 1
BP S15
EP S15
PG 1
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 895VN
UT WOS:000300524900037
ER
PT J
AU Stangl, BL
Zametkin, M
Vatsalya, V
Ramchandani, VA
AF Stangl, B. L.
Zametkin, M.
Vatsalya, V.
Ramchandani, V. A.
TI CHARACTERIZATION OF OPERANT INTRAVENOUS (IV) ETHANOL SELF-ADMINISTRATION
IN HUMANS: OPEN-BAR AND PROGRESSIVE-RATIO PARADIGMS.
SO CLINICAL PHARMACOLOGY & THERAPEUTICS
LA English
DT Meeting Abstract
CT 113th Annual Meeting of the
American-Society-for-Clinical-Pharmacology-and-Therapeutics (ASCPT)
CY MAR 14-17, 2012
CL Natl Harbor, MD
SP Amer Soc Clin Pharmacol & Therapeut (ASCPT)
C1 [Stangl, B. L.; Zametkin, M.; Vatsalya, V.; Ramchandani, V. A.] NIAAA, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0009-9236
J9 CLIN PHARMACOL THER
JI Clin. Pharmacol. Ther.
PD MAR
PY 2012
VL 91
SU 1
BP S56
EP S56
PG 1
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 895VN
UT WOS:000300524900146
ER
PT J
AU Tai, W
Gong, SL
Tsunoda, SM
Greenberg, HE
Gorski, JC
Penzak, SR
Stoch, SA
Ma, JD
AF Tai, W.
Gong, S. L.
Tsunoda, S. M.
Greenberg, H. E.
Gorski, J. C.
Penzak, S. R.
Stoch, S. A.
Ma, J. D.
TI ORAL MIDAZOLAM (MDZ) PARTIAL AREA-UNDER CURVE (AUC) DOES NOT RELIABLY
PREDICT CYTOCHROME P450 (CYP) 3A BASELINE ACTIVITY IN HEALTHY SUBJECTS.
SO CLINICAL PHARMACOLOGY & THERAPEUTICS
LA English
DT Meeting Abstract
CT 113th Annual Meeting of the
American-Society-for-Clinical-Pharmacology-and-Therapeutics (ASCPT)
CY MAR 14-17, 2012
CL Natl Harbor, MD
SP Amer Soc Clin Pharmacol & Therapeut (ASCPT)
C1 [Tai, W.; Gong, S. L.; Tsunoda, S. M.; Ma, J. D.] UCSD, Skaggs Sch Pharm & Pharmaceut Sci, La Jolla, CA USA.
[Greenberg, H. E.] Thomas Jefferson Univ, Dept Pharmacol & Expt Therapeut, Philadelphia, PA 19107 USA.
[Gorski, J. C.] Mylan Pharmaceut, Morgantown, WV USA.
[Penzak, S. R.] NIH, Dept Pharm, Bethesda, MD 20892 USA.
[Stoch, S. A.] Merck, Rahway, NJ USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0009-9236
J9 CLIN PHARMACOL THER
JI Clin. Pharmacol. Ther.
PD MAR
PY 2012
VL 91
SU 1
BP S42
EP S42
PG 1
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 895VN
UT WOS:000300524900109
ER
PT J
AU Vatsalya, V
Stangl, B
Zametkin, M
Ramchandani, VA
AF Vatsalya, V.
Stangl, B.
Zametkin, M.
Ramchandani, V. A.
TI SKIN BLOOD FLOW (SBF) RESPONSE FOLLOWING ACUTE INTRAVENOUS (IV) ETHANOL
AND ASSOCIATION WITH SUBJECTIVE RESPONSES IN SOCIAL DRINKERS.
SO CLINICAL PHARMACOLOGY & THERAPEUTICS
LA English
DT Meeting Abstract
CT 113th Annual Meeting of the
American-Society-for-Clinical-Pharmacology-and-Therapeutics (ASCPT)
CY MAR 14-17, 2012
CL Natl Harbor, MD
SP Amer Soc Clin Pharmacol & Therapeut (ASCPT)
C1 [Vatsalya, V.; Stangl, B.; Zametkin, M.; Ramchandani, V. A.] NIAAA, NIH, Bethesda, MD USA.
NR 0
TC 0
Z9 0
U1 0
U2 0
PU NATURE PUBLISHING GROUP
PI NEW YORK
PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA
SN 0009-9236
J9 CLIN PHARMACOL THER
JI Clin. Pharmacol. Ther.
PD MAR
PY 2012
VL 91
SU 1
BP S128
EP S128
PG 1
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 895VN
UT WOS:000300524900340
ER
PT J
AU Li Bassi, G
Saucedo, L
Marti, JD
Rigol, M
Esperatti, M
Luque, N
Ferrer, M
Gabarrus, A
Fernandez, L
Kolobow, T
Torres, A
AF Li Bassi, Gianluigi
Saucedo, Lina
Marti, Joan-Daniel
Rigol, Montserrat
Esperatti, Mariano
Luque, Nestor
Ferrer, Miguel
Gabarrus, Albert
Fernandez, Laia
Kolobow, Theodor
Torres, Antoni
TI Effects of duty cycle and positive end-expiratory pressure on mucus
clearance during mechanical ventilation
SO CRITICAL CARE MEDICINE
LA English
DT Article
DE intensive care; intrinsic positive end-expiratory pressure; mechanical
ventilation; mucociliary clearance; peak expiratory flow rate; positive
end-expiratory pressure
ID LIQUID FLOW MECHANISM; RESPIRATORY MECHANICS; CHEST PHYSIOTHERAPY;
CYSTIC-FIBROSIS; TRANSPORT; AIRWAYS; MODEL
AB Objectives: During mechanical ventilation, air flows may play a role in mucus transport via two-phase gas liquid flow. The aim of this study was to evaluate effects of duty cycles and positive end-expiratory pressure on mucus clearance in pigs using mechanical ventilation, and to assess their safety.
Design: Prospective randomized animal study.
Setting: Animal research facility, University of Barcelona, Spain.
Subjects: Eight healthy pigs.
Interventions: Pigs were intubated and on volume-control mechanical ventilation for up to 84 hrs. After 4, 24, 48, and 72 hrs of mechanical ventilation, six levels of duty cycle (0.26, 0.33, 0.41, 0.50, 0.60, and 0.75) with no associated positive end-expiratory pressure or 5 cm H2O of positive end-expiratory pressure were randomly applied. Surgical bed was oriented 30 degrees in the reverse Trendelenburg position, as in the semirecumbent position.
Measurement and Main Results: Inspiratory and expiratory flows and hemodynamics were measured after each 30-min ventilation period. Mucus movement was assessed through fluoroscopy tracking of radio-opaque markers. Mucus velocity was described by a positive vector (toward the glottis) or negative vector (toward the lungs). No effect of positive end-expiratory pressure was found; however, as duty cycle was increasingly prolonged, a trend toward reduced velocity of mucus moving toward the lungs and increased outward mucus velocity was found (p = .064). Two clusters of mucus velocities were identified as duty cycle was prolonged beyond 0.41. Thus, duty cycle >0.41 increased mean expiratory inspiratory flow bias from -4.1 +/- 4.6 to 7.9 +/- 5.9 L/min (p < .0001) and promoted outward mucus velocity from -0.22 +/- 1.71 mm/min (range, -5.78 to 2.42) to 0.53 +/- 1.06 mm/min (-1.91 to 3.88; p = .0048). Duty cycle of 0.75 resulted in intrinsic positive end-expiratory pressure (2.1 +/- 1.1 cm H2O [p < .0001] vs. duty cycle 0.26-0.5), with no hemodynamic compromise.
Conclusions: In the semirecumbent position, mucus clearance is improved with prolongation of the duty cycle. However, in clinical practice, positive findings must be balanced against the potentially adverse hemodynamic and respiratory effects. (Crit Care Med 2012; 40:895-902)
C1 [Gabarrus, Albert; Torres, Antoni] Hosp Clin Barcelona, Thorax Inst, Dept Pneumol, Off Biostat, Barcelona, Spain.
[Li Bassi, Gianluigi; Rigol, Montserrat; Ferrer, Miguel; Fernandez, Laia; Torres, Antoni] Inst Invest Biomed August Pi i Sunyer, Barcelona, Spain.
[Li Bassi, Gianluigi; Rigol, Montserrat; Esperatti, Mariano; Ferrer, Miguel; Gabarrus, Albert; Fernandez, Laia; Torres, Antoni] Ctr Invest Biomed Red Enfermedades Resp, Barcelona, Spain.
[Rigol, Montserrat] Hosp Clin Barcelona, Thorax Inst, Dept Cardiol, Barcelona, Spain.
[Kolobow, Theodor] NHLBI, Pulm & Crit Care Med Branch, Sect Pulm & Cardiac Assist Devices, NIH, Bethesda, MD 20892 USA.
[Torres, Antoni] Univ Barcelona, Barcelona, Spain.
RP Torres, A (reprint author), Hosp Clin Barcelona, Thorax Inst, Dept Pneumol, Off Biostat, Barcelona, Spain.
EM atorres@clinic.ub.es
FU Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS),
Ministerio de Ciencia e Innovacion [PS09/01249]; European Society of
Intensive Care Medicine- ESICM; Fundacio Catalana de Pneumologia
(FUCAP); Sociedad Espanola de Neumologia y Cirugia Toracica (SEPAR);
Centro de Investigacion Biomedica En Red- Enfermedades Respiratorias,
(CIBERES); HERACLES [RD06/0009/0008]
FX Supported, in part, by the Institut d'Investigacions Biomediques August
Pi i Sunyer (IDIBAPS), Ministerio de Ciencia e Innovacion (PS09/01249);
European Society of Intensive Care Medicine- ESICM (2009 Alain Hart
Award on Applied Respiratory Physiology); Fundacio Catalana de
Pneumologia (FUCAP); Sociedad Espanola de Neumologia y Cirugia Toracica
(SEPAR); and Centro de Investigacion Biomedica En Red- Enfermedades
Respiratorias, (CIBERES); and HERACLES, RD06/0009/0008.
NR 20
TC 11
Z9 11
U1 1
U2 7
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0090-3493
J9 CRIT CARE MED
JI Crit. Care Med.
PD MAR
PY 2012
VL 40
IS 3
BP 895
EP 902
DI 10.1097/CCM.00013e318236efb5
PG 8
WC Critical Care Medicine
SC General & Internal Medicine
GA 895YO
UT WOS:000300532800025
PM 22080638
ER
PT J
AU Ackerman, HC
Carroll, RW
Casals-Pascual, C
AF Ackerman, Hans C.
Carroll, Ryan W.
Casals-Pascual, Climent
TI A better biomarker for cerebral malaria: In the eye of the beheld?
SO CRITICAL CARE MEDICINE
LA English
DT Editorial Material
DE angiopoietin; biomarker; cerebral malaria; endothelium; malaria; nitric
oxide; retinopathy; sensitivity; specificity
ID FALCIPARUM-MALARIA; AFRICAN CHILDREN; NITRIC-OXIDE; ANGIOPOIETIN-2;
INDICATORS; LIGAND; TIE2
C1 [Ackerman, Hans C.] NIAID, Lab Malaria & Vector Res, Rockville, MD 20892 USA.
[Carroll, Ryan W.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Div Pediat Crit Care Med, Boston, MA USA.
[Carroll, Ryan W.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Anesthesiol Ctr Crit Care Res, Boston, MA USA.
[Casals-Pascual, Climent] Wellcome Trust Ctr Human Genet, Oxford, England.
RP Ackerman, HC (reprint author), NIAID, Lab Malaria & Vector Res, Rockville, MD 20892 USA.
FU Intramural NIH HHS [ZIA AI001150-02]; Medical Research Council
[G0701885]
NR 18
TC 0
Z9 0
U1 1
U2 3
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0090-3493
J9 CRIT CARE MED
JI Crit. Care Med.
PD MAR
PY 2012
VL 40
IS 3
BP 1018
EP 1020
DI 10.1097/CCM.0b013e31823d7810
PG 3
WC Critical Care Medicine
SC General & Internal Medicine
GA 895YO
UT WOS:000300532800063
PM 22343865
ER
PT J
AU Beigel, JH
Luke, TC
AF Beigel, John H.
Luke, Thomas C.
TI A study in scarlet-convalescent plasma for severe influenza
SO CRITICAL CARE MEDICINE
LA English
DT Editorial Material
DE convalescent; H1N1; H5N1; influenza; passive immunotherapy; plasma;
treatment
ID H1N1 VIRUS-INFECTION; OSELTAMIVIR; RESISTANT; THERAPY; CANADA
C1 [Beigel, John H.] NIAID, Div Intramural Res, SAIC Frederick Inc, NCI Frederick, Frederick, MD 21701 USA.
[Luke, Thomas C.] USN, Med Res Ctr, Henry Jackson Fdn, Virol & Rickettsial Dis Div, Silver Spring, MD USA.
RP Beigel, JH (reprint author), NIAID, Div Intramural Res, SAIC Frederick Inc, NCI Frederick, Frederick, MD 21701 USA.
FU CCR NIH HHS [HHSN261200800001C]; Intramural NIH HHS [Z99 AI999999]; NCI
NIH HHS [HHSN261200800001E]
NR 14
TC 3
Z9 3
U1 0
U2 2
PU LIPPINCOTT WILLIAMS & WILKINS
PI PHILADELPHIA
PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA
SN 0090-3493
J9 CRIT CARE MED
JI Crit. Care Med.
PD MAR
PY 2012
VL 40
IS 3
BP 1027
EP 1028
DI 10.1097/CCM.0b013e31823d77c3
PG 2
WC Critical Care Medicine
SC General & Internal Medicine
GA 895YO
UT WOS:000300532800069
PM 22343871
ER
PT J
AU Degheidy, HA
Venzon, DJ
Farooqui, MZH
Abbasi, F
Arthur, DC
Wilson, WH
Wiestner, A
Stetler-Stevenson, MA
Marti, GE
AF Degheidy, Heba A.
Venzon, David J.
Farooqui, Mohammed Z. H.
Abbasi, Fatima
Arthur, Diane C.
Wilson, Wyndham H.
Wiestner, Adrian
Stetler-Stevenson, M. A.
Marti, Gerald E.
TI Combined normal donor and CLL: Single tube ZAP-70 analysis
SO CYTOMETRY PART B-CLINICAL CYTOMETRY
LA English
DT Article
DE chronic lymphocytic leukemia; ZAP-70; flow cytometry; one tube assay;
IGHV; cytogenetics
ID CHRONIC LYMPHOCYTIC-LEUKEMIA; GENE MUTATION STATUS; GENOMIC ABERRATIONS;
PROGNOSTIC-FACTORS; CD38 EXPRESSION; DIAGNOSIS; SURVIVAL; RATIO
AB Introduction: Zeta-chain-associated protein kinase 70 (ZAP-70) has been identified as an independent prognostic marker in chronic lymphocytic leukemia (CLL). Based on our previous studies, we have developed a combined one-tube technology with multiple internal controls to optimize ZAP-70 assessment.
Methods: Forty-eight untreated CLL cases were examined for ZAP-70 expression using a modified 7-color one-tube assay. Normal donor (ND) whole blood is stained with CD3 APC-Cy7 and CD19 APC. In a second tube, patient whole blood is stained with CD5 PE-Cy7, CD19 PerCP-Cy5.5, and CD20 eFluor450. After surface staining and fixation, these two tubes are combined. After saponin permeabilization, the cells were stained with two anti-ZAP-70 clones (1E7.2/AF488 and SBZAP/PE). The results obtained from this modified tube were compared with those obtained concurrently using the non-mixed single sample tubes. Five different methods of ZAP-70 expression analysis were evaluated: percentage positive cells using ND T-cells as a reference; the internal patient T-cell/clone ratio; ND T-cell/clone ratio; clone/ND B-cell ratio; and modified Z-index.
Result: Overall, the combined patient and ND mix tube performed better than the non-mixed single sample tube. The strongest correlations between ZAP-70 expression and immunoglobulin heavy chain variable (IGHV) mutational status were seen with percentage positive ND T-cell, ND T-cell/clone ratio, and clone/ND B-cell ratio for both 1E7.2 and SBZAP clone (P < 0.0001).
Conclusion: The modified one tube method combining the ND and patient sample provides highly reliable results that correlate with the IGHV mutational status. This method should be considered as part of the next step in standardization of the ZAP-70 assay in CLL. Published 2011 Wiley Periodicals, Inc.(dagger)
C1 [Farooqui, Mohammed Z. H.; Wiestner, Adrian] NHLBI, NIH, Bethesda, MD 20892 USA.
[Arthur, Diane C.; Stetler-Stevenson, M. A.] NCI, Pathol Lab, Bethesda, MD 20892 USA.
[Wilson, Wyndham H.] NCI, Metab Branch, Bethesda, MD 20892 USA.
[Venzon, David J.] NCI, Biostat & Data Management Sect, Bethesda, MD 20892 USA.
[Degheidy, Heba A.; Abbasi, Fatima; Marti, Gerald E.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA.
RP Marti, GE (reprint author), OIVD DIHD CDRH, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA.
EM gemarti@mac.com
FU NHLBI; NIH; CBER/FDA
FX Grant sponsor: Intramural Research Program of the NHLBI, NIH and
CBER/FDA.
NR 21
TC 2
Z9 2
U1 0
U2 1
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1552-4949
J9 CYTOM PART B-CLIN CY
JI Cytom. Part B-Clin. Cytom.
PD MAR
PY 2012
VL 82B
IS 2
BP 67
EP 77
DI 10.1002/cyto.b.20622
PG 11
WC Medical Laboratory Technology; Pathology
SC Medical Laboratory Technology; Pathology
GA 897WT
UT WOS:000300692000003
PM 22031337
ER
PT J
AU Chitnis, AB
Nogare, DD
Matsuda, M
AF Chitnis, Ajay B.
Nogare, Damian Dalle
Matsuda, Miho
TI Building the posterior lateral line system in zebrafish
SO DEVELOPMENTAL NEUROBIOLOGY
LA English
DT Review
DE lateral line; zebrafish; pattern formation; self-organization;
neuromasts
ID COLLECTIVE CELL-MIGRATION; CHEMOKINE RECEPTOR CXCR4; HAIR-CELLS;
DANIO-RERIO; POSTEMBRYONIC DEVELOPMENT; APICAL CONSTRICTION;
WNT/BETA-CATENIN; TISSUE MIGRATION; LARVAL ZEBRAFISH; BETA-ARRESTIN
AB The posterior lateral line (pLL) in zebrafish has emerged as an excellent system to study how a sensory organ system develops. Here we review recent studies that illustrate how interactions between multiple signaling pathways coordinate cell fate, morphogenesis, and collective migration of cells in the posterior lateral line primordium. These studies also illustrate how the pLL system is contributing much more broadly to our understanding of mechanisms operating during the growth, regeneration, and self-organization of other organ systems during development and disease. (c) 2011 Wiley Periodicals, Inc. Develop Neurobiol 72: 234255, 2012
C1 [Chitnis, Ajay B.; Nogare, Damian Dalle; Matsuda, Miho] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Genom Dev, NIH, Bethesda, MD USA.
RP Chitnis, AB (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Program Genom Dev, NIH, Bethesda, MD USA.
EM chitnisa@mail.nih.gov
FU Intramural NIH HHS [ZIA HD001012-14]; NICHD NIH HHS [R00 HD062561]
NR 97
TC 35
Z9 35
U1 1
U2 10
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 1932-8451
J9 DEV NEUROBIOL
JI Dev. Neurobiol.
PD MAR
PY 2012
VL 72
IS 3
SI SI
BP 234
EP 255
DI 10.1002/dneu.20962
PG 22
WC Developmental Biology; Neurosciences
SC Developmental Biology; Neurosciences & Neurology
GA 894MA
UT WOS:000300429600003
PM 21818862
ER
PT J
AU Rosell, M
Hondares, E
Iwamoto, S
Gonzalez, FJ
Wabitsch, M
Staels, B
Olmos, Y
Monsalve, M
Giralt, M
Iglesias, R
Villarroya, F
AF Rosell, Meritxell
Hondares, Elayne
Iwamoto, Sadahiko
Gonzalez, Frank J.
Wabitsch, Martin
Staels, Bart
Olmos, Yolanda
Monsalve, Maria
Giralt, Marta
Iglesias, Roser
Villarroya, Francesc
TI Peroxisome Proliferator-Activated Receptors-alpha and -gamma, and
cAMP-Mediated Pathways, Control Retinol-Binding Protein-4 Gene
Expression in Brown Adipose Tissue
SO ENDOCRINOLOGY
LA English
DT Article
ID INSULIN-RESISTANCE; PPAR-ALPHA; RETINOL-BINDING-PROTEIN-4 PRODUCTION;
SERUM RETINOL-BINDING-PROTEIN-4; DIABETIC SUBJECTS; ACID; TRANSCRIPTION;
FAT; DIFFERENTIATION; CELL
AB Retinol binding protein-4 (RBP4) is a serum protein involved in the transport of vitamin A. It is known to be produced by the liver and white adipose tissue. RBP4 release by white fat has been proposed to induce insulin resistance. We analyzed the regulation and production of RBP4 in brown adipose tissue. RBP4 gene expression is induced in brown fat from mice exposed to cold or treated with peroxisome proliferator-activated receptor(PPAR) agonists. In brown adipocytes in culture, norepinephrine, cAMP, and activators of PPAR gamma and PPAR alpha induced RBP4 gene expression and RBP4 protein release. The induction of RBP4 gene expression by norepinephrine required intact PPAR-dependent pathways, as evidenced by impaired response of the RBP4 gene expression to norepinephrine in PPAR alpha-null brown adipocytes or in the presence of inhibitors of PPAR gamma and PPAR alpha. PPAR gamma and norepinephrine can also induce the RBP4 gene in white adipocytes, and over expression of PPAR alpha confers regulation by this PPAR subtype to white adipocytes. The RBP4 gene promoter transcription is activated by cAMP, PPAR alpha, and PPAR gamma. This is mediated by a PPAR-responsive element capable of binding PPAR alpha and PPAR gamma and required also for activation by cAMP. The induction of the RBP4 gene expression by norepinephrine in brown adipocytes is protein synthesis dependent and requires PPAR gamma-coactivator-1-alpha, which acts as a norepinephine-induced coactivator of PPAR on the RBP4 gene. We conclude that PPAR gamma- and PPAR alpha-mediated signaling controls RBP4 gene expression and releases in brown adipose tissue, and thermogenic activation induces RBP4 gene expression in brown fat through mechanisms involving PPAR gamma-coactivator-1-alpha coactivation of PPAR signaling. (Endocrinology 153: 1162-1173, 2012)
C1 [Rosell, Meritxell; Hondares, Elayne; Giralt, Marta; Iglesias, Roser; Villarroya, Francesc] Univ Barcelona, Dept Bioquim & Biol Mol, Inst Biomed, E-08028 Barcelona, Spain.
Ctr Invest Biomed Red Fisiopatol Obesidad & Nutr, E-08028 Barcelona, Spain.
[Iwamoto, Sadahiko] Jichi Med Univ, Div Human Genet, Shimotsuke, Tochigi 3290498, Japan.
[Gonzalez, Frank J.] NCI, Lab Metab, Bethesda, MD 20892 USA.
[Wabitsch, Martin] Univ Ulm, Dept Pediat & Adolescent Med, D-89075 Ulm, Germany.
[Staels, Bart] Univ Lille Nord France, INSERM, U1011, Inst Pasteur Lille, F-59019 Lille, France.
[Olmos, Yolanda; Monsalve, Maria] Inst Salud Carlos III, Ctr Nacl Invest Cardiovasc, Madrid 28029, Spain.
Consejo Super Invest Cient, Inst Invest Biomed Alberto Sols, Madrid 28029, Spain.
RP Villarroya, F (reprint author), Univ Barcelona, Dept Bioquim & Biol Mol, Inst Biomed, Avinguda Diagonal 643, E-08028 Barcelona, Spain.
EM fvillarroya@ub.edu
RI Giralt, Marta/A-4756-2013; Villarroya, Francesc/K-4357-2014;
OI Giralt, Marta/0000-0001-7968-4190; Staels, Bart/0000-0002-3784-1503
FU Ministerio de Ciencia e Innovacion [SAF2008-01896, SAF2011-23636]; Fondo
de Investigaciones Sanitarias, Spain [PI081715]; European Union
[HEALTH-F2-2011-277713]
FX This work was supported by the Ministerio de Ciencia e Innovacion Grant
SAF2008-01896, SAF2011-23636 and Fondo de Investigaciones Sanitarias
Grant PI081715, Spain. Centro de Investigacion Biomedica en Red
Fisiopatologia de la Obesidad y Nutricion is an initiative of Instituto
de Salud Carlos III Spain, and Grant HEALTH-F2-2011-277713 by the
European Union.
NR 45
TC 15
Z9 15
U1 0
U2 5
PU ENDOCRINE SOC
PI CHEVY CHASE
PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA
SN 0013-7227
J9 ENDOCRINOLOGY
JI Endocrinology
PD MAR
PY 2012
VL 153
IS 3
BP 1162
EP 1173
DI 10.1210/en.2011-1367
PG 12
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 897JG
UT WOS:000300645600022
PM 22253419
ER
PT J
AU Pang, XY
Cheng, J
Kim, JH
Matsubara, T
Krausz, KW
Gonzalez, FJ
AF Pang, Xiao-Yan
Cheng, Jie
Kim, Jung-Hwan
Matsubara, Tsutomu
Krausz, Kristopher W.
Gonzalez, Frank J.
TI Expression and Regulation of Human Fetal-Specific CYP3A7 in Mice
SO ENDOCRINOLOGY
LA English
DT Article
ID PREGNANE X-RECEPTOR; ADULT HUMAN LIVER; DEHYDROEPIANDROSTERONE-SULFATE;
CYTOCHROMES P450; PRIMARY CULTURE; GENE; HEPATOCYTES; INDUCTION;
ELEMENT; MOUSE
AB CYP3A7 is the predominant cytochrome P450 (CYP) expressed in human fetal liver, accounting for 30-50% of the total CYP in fetal liver and 87-100% of total fetal hepatic CYP3A content. However, the lack of a rodent model limits the investigation of CYP3A7 regulation and function. Hence, double-transgenic mice expressing human pregnane X receptor (PXR) and CYP3A4/7 (Tg3A4/7-hPXR) were used to investigate the regulation and function of CYP3A7. Expression of CYP3A7 was monitored in mice that ranged in age from 14.5-d-old embryos to 8.5-d-old newborns; expression of CYP3A7 mRNA was increased before birth in the embryos and decreased after birth in the newborns. This is consistent with the observed developmental regulation of CYP3A7 protein levels and CYP3A7-mediated dehydroepiandrosterone 16 alpha-hydroxylase activities. This developmental flux is also in agreement with previous studies that have investigated the expression of CYP3A7 in developing human liver. The regulation of CYP3A7 was further studied using hepatoblasts from the Tg3A4/7-hPXR mice. Glucocorticoids, including dexamethasone, cortisol, corticosterone, and cortisone all induced the expression of CYP3A7 mRNA, whereas rifampicin, an activator of PXR and an inducer of CYP3A4 in adult liver, had no effect on CYP3A7 expression. Cell-based promoter luciferase and chromatin immunoprecipitation assays further confirmed glucocorticoid receptor-mediated control of the CYP3A7 promoter. These findings indicate that CYP3A7 is developmentally regulated in mouse liver primarily by glucocorticoids through the glucocorticoid receptor. The Tg3A4/7-hPXR mouse model could therefore potentially serve as a tool for investigating CYP3A7 regulation and function. (Endocrinology 153: 1453-1463, 2012)
C1 [Pang, Xiao-Yan; Cheng, Jie; Kim, Jung-Hwan; Matsubara, Tsutomu; Krausz, Kristopher W.; Gonzalez, Frank J.] NCI, Lab Metab, NIH, Bethesda, MD 20892 USA.
RP Gonzalez, FJ (reprint author), NCI, Lab Metab, NIH, Bldg 37,Room 3106, Bethesda, MD 20892 USA.
EM gonzalef@mail.nih.gov
FU National Cancer Institute; China Scholarship Council
FX This work was supported by the National Cancer Institute Intramural
Research Program. X.-Y.P. was partially supported by a fellowship from
China Scholarship Council. We thank Caroline H. Johnson for careful
review of the manuscript, and John Buckley and Linda G Byrd for
assistance with the mouse studies.
NR 41
TC 10
Z9 11
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
J9 ENDOCRINOLOGY
JI Endocrinology
PD MAR
PY 2012
VL 153
IS 3
BP 1453
EP 1463
DI 10.1210/en.2011-1020
PG 11
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 897JG
UT WOS:000300645600048
PM 22253426
ER
PT J
AU Cordas, EA
Ng, L
Hernandez, A
Kaneshige, M
Cheng, SY
Forrest, D
AF Cordas, Emily A.
Ng, Lily
Hernandez, Arturo
Kaneshige, Masahiro
Cheng, Sheue-Yann
Forrest, Douglas
TI Thyroid Hormone Receptors Control Developmental Maturation of the Middle
Ear and the Size of the Ossicular Bones
SO ENDOCRINOLOGY
LA English
DT Article
ID CONDUCTIVE HEARING-LOSS; OTITIS-MEDIA; CONGENITAL HYPOTHYROIDISM;
STRUCTURAL MATURATION; EARLY HYPOPHYSECTOMY; TEMPORAL BONES; NULL MICE;
MESENCHYME; MUTATION; RESISTANCE
AB Thyroid hormone is critical for auditory development and has well-known actions in the inner ear. However, less is known of thyroid hormone functions in the middle ear, which contains the ossicles (malleus, incus, stapes) that relay mechanical sound vibrations from the outer ear to the inner ear. During the later stages of middle ear development, prior to the onset of hearing, middle ear cavitation occurs, involving clearance of mesenchyme from the middle ear cavity while the immature cartilaginous ossicles attain appropriate size and ossify. Using in situ hybridization, we detected expression of Thra and Thrb genes encoding thyroid hormone receptors alpha 1 and beta (TR alpha 1 and TR beta, respectively) in the immature ossicles, surrounding mesenchyme and tympanic membrane in the mouse. Thra(+/PV) mice that express a dominant-negative TR alpha 1 protein exhibited deafness with elevated auditory thresholds and a range of middle ear abnormalities including chronic persistence of mesenchyme in the middle ear into adulthood, markedly enlarged ossicles, and delayed ossification of the ossicles. Congenitally hypothyroid Tshr(-/-) mice and TR-deficient Thra1(-/-); Thrb(-/-) mice displayed similar abnormalities. These findings demonstrate that middle ear maturation is TR dependent and suggest that the middle ear is a sensitive target for thyroid hormone in development. (Endocrinology 153: 1548-1560, 2012)
C1 [Forrest, Douglas] NIDDKD, Lab Endocrinol & Receptor Biol, NIH, Bethesda, MD 20892 USA.
[Kaneshige, Masahiro; Cheng, Sheue-Yann] NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.
[Hernandez, Arturo] Dartmouth Med Sch, Dept Physiol, Lebanon, NH 03756 USA.
RP Forrest, D (reprint author), NIDDKD, Lab Endocrinol & Receptor Biol, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA.
EM forrestd@niddk.nih.gov
FU National Institutes of Health at the National Institute of Diabetes and
Digestive and Kidney Diseases; National Cancer Institute
FX This work was supported by the intramural research program of the
National Institutes of Health at the National Institute of Diabetes and
Digestive and Kidney Diseases and the National Cancer Institute.
NR 60
TC 12
Z9 12
U1 0
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 MAR
PY 2012
VL 153
IS 3
BP 1548
EP 1560
DI 10.1210/en.2011-1834
PG 13
WC Endocrinology & Metabolism
SC Endocrinology & Metabolism
GA 897JG
UT WOS:000300645600057
PM 22253431
ER
PT J
AU Chambers, SK
Girgis, A
Occhipinti, S
Hutchison, S
Turner, J
Morris, B
Dunn, J
AF Chambers, S. K.
Girgis, A.
Occhipinti, S.
Hutchison, S.
Turner, J.
Morris, B.
Dunn, J.
TI Psychological distress and unmet supportive care needs in cancer
patients and carers who contact cancer helplines
SO EUROPEAN JOURNAL OF CANCER CARE
LA English
DT Article
DE psychological distress; cancer; supportive care needs; intervention;
telephone information service
ID INFORMATION-SERVICE; BREAST-CANCER; TELEPHONE HELPLINE; THERMOMETER;
INTERVENTION; VALIDATION; IMPACT; MODEL; EXPERIENCE; SYMPTOMS
AB Cancer information services are a highly accessible source of support for people affected by cancer. To date the nature and extent of distress experienced by such callers and their unmet support needs have not been well described. A cross-sectional survey of 354 cancer patients and 336 carers who reported elevated distress on contact with a cancer information service assessed socio-demographic variables; anxiety, depression and somatization; unmet supportive care needs; cancer-specific distress; presenting problems; post-traumatic growth. Adjustment to cancer was most commonly reported; followed by anxiety. In all, 53.4% of patients and 45.2% of carers reached caseness in anxiety, depression or somatization. Carers had higher distress ratings and intrusive thinking compared to patients; whereas patients had higher somatization. For patients, most unmet supportive care needs were psychological; for carers unmet needs were related to health care services and information related to the person diagnosed with cancer. Being single, unemployed, in treatment, having higher initial distress scores, higher intrusion and avoidance predicted poorer outcomes. Information service frameworks should include distress screening and clear triage and referral processes for psychological care.
C1 [Chambers, S. K.; Occhipinti, S.; Dunn, J.] Griffith Univ, Griffith Hlth Inst, Gold Coast, Qld, Australia.
[Chambers, S. K.; Hutchison, S.; Morris, B.; Dunn, J.] Canc Council Queensland, Viertel Ctr Res Canc Control, Brisbane, Qld, Australia.
[Chambers, S. K.] Univ Queensland, Clin Res Ctr, Brisbane, Qld, Australia.
[Girgis, A.] Univ Newcastle, Newcastle, NSW 2300, Australia.
[Turner, J.] Univ Queensland, Sch Med, Brisbane, Qld, Australia.
[Morris, B.] NIH, Bethesda, MD 20892 USA.
[Dunn, J.] Univ Queensland, Sch Social Sci, Brisbane, Qld, Australia.
RP Chambers, SK (reprint author), Griffith Hlth Inst, POB 201, Spring Hill, Qld 4004, Australia.
EM suzanne.chambers@griffith.edu.au
RI Chambers, Suzanne/H-5957-2012; Dunn, Jeff/H-6002-2012; Turner,
Jane/F-4838-2010; Occhipinti, Stefano/G-3361-2015
OI Turner, Jane/0000-0003-1438-217X; Occhipinti,
Stefano/0000-0002-2558-0609
FU beyondblue, Cancer Australia [APP561701]; Cancer Council Queensland and
New South Wales
FX This project was funded by beyondblue, Cancer Australia (APP561701),
Cancer Council Queensland and New South Wales. We thank Barbara Haddon
for research management support, Samantha Clutton and Brigid Hanley for
clinical input, Megan Ferguson for manuscript preparation support and
Paula Vallentine for project support in New South Wales.
NR 59
TC 28
Z9 30
U1 2
U2 16
PU WILEY-BLACKWELL
PI HOBOKEN
PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
SN 0961-5423
J9 EUR J CANCER CARE
JI Eur. J. Cancer Care
PD MAR
PY 2012
VL 21
IS 2
BP 213
EP 223
DI 10.1111/j.1365-2354.2011.01288.x
PG 11
WC Oncology; Health Care Sciences & Services; Nursing; Rehabilitation
SC Oncology; Health Care Sciences & Services; Nursing; Rehabilitation
GA 895LY
UT WOS:000300498900009
PM 21895814
ER
PT J
AU Gaskins, AJ
Mumford, SL
Wactawski-Wende, J
Schisterman, EF
AF Gaskins, Audrey J.
Mumford, Sunni L.
Wactawski-Wende, Jean
Schisterman, Enrique F.
TI Effect of daily fiber intake on luteinizing hormone levels in
reproductive-aged women
SO EUROPEAN JOURNAL OF NUTRITION
LA English
DT Article
DE Dietary fiber; Luteinizing hormone; Estradiol; Women
ID MENSTRUAL-CYCLE; DIETARY FIBER; BIOCYCLE; LEPTIN
AB To evaluate whether the association between fiber intake and LH levels is driven by the association between fiber and estradiol, or whether there is an independent association.
A prospective cohort of 259 premenopausal women were followed for up to 2 menstrual cycles. Estrogen and LH were measured a parts per thousand currency sign8 times per cycle at visits scheduled using fertility monitors. Diet was assessed a parts per thousand currency sign4 times per cycle by 24-h recall. Linear mixed models on the log scale of hormones were utilized to evaluate the total effects of fiber intake. Inverse probability weights were utilized to estimate the independent effect of fiber on LH levels.
In unweighted analyses, we observed a significant, inverse association between fiber intake (in 5 g/day increments) and log LH levels (beta, -0.051, 95% confidence interval (CI), -0.100, -0.002). No association was observed in the weighted analyses, after estradiol levels were taken into account (beta, -0.016, 95% CI, -0.060, 0.027).
The decreased levels of LH associated with high fiber intake were attenuated after taking estradiol levels into account, suggesting that the association between fiber and LH is most likely a consequence of fiber's impact on estradiol and not due to an independent mechanism.
C1 [Gaskins, Audrey J.; Mumford, Sunni L.; Schisterman, Enrique F.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, Rockville, MD 20852 USA.
[Wactawski-Wende, Jean] SUNY Buffalo, Dept Social & Preventat Med, Buffalo, NY 14260 USA.
RP Schisterman, EF (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent Res, 6100 Execut Blvd,7B03M, Rockville, MD 20852 USA.
EM schistee@mail.nih.gov
OI Schisterman, Enrique/0000-0003-3757-641X
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development (NICHD)
FX Funding: The BioCycle study and their researchers were supported by the
Intramural Research Program of the Eunice Kennedy Shriver National
Institute of Child Health and Human Development (NICHD). Contributors:
The authors thank all the investigators and staff at the University at
Buffalo and NICHD for their respective roles in the study, specifically
Cuilin Zhang, Kathleen M. Hovey, Brian W. Whitcomb, Penelope P. Howards,
Neil J. Perkins, and Edwina Yeung.
NR 12
TC 2
Z9 2
U1 0
U2 5
PU SPRINGER HEIDELBERG
PI HEIDELBERG
PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY
SN 1436-6207
J9 EUR J NUTR
JI Eur. J. Nutr.
PD MAR
PY 2012
VL 51
IS 2
BP 249
EP 253
DI 10.1007/s00394-011-0207-2
PG 5
WC Nutrition & Dietetics
SC Nutrition & Dietetics
GA 896EW
UT WOS:000300549200014
PM 21667182
ER
PT J
AU Zhang, Y
Crous, PW
Schoch, CL
Hyde, KD
AF Zhang, Ying
Crous, Pedro W.
Schoch, Conrad L.
Hyde, Kevin D.
TI Pleosporales
SO FUNGAL DIVERSITY
LA English
DT Article
DE Generic type; Massarineae; Molecular phylogeny; Morphology;
Pleosporales; Taxonomy
ID RIBOSOMAL DNA-SEQUENCES; AUSTRALIAN FRESH-WATER; INTERTIDAL MANGROVE
WOOD; SP-NOV; NORTH-AMERICA; MARINE FUNGI; MOLECULAR PHYLOGENY;
TREMATOSPHAERIA-CIRCINANS; SHIRAIA-BAMBUSICOLA; MULTIGENE PHYLOGENY
AB One hundred and five generic types of Pleosporales are described and illustrated. A brief introduction and detailed history with short notes on morphology, molecular phylogeny as well as a general conclusion of each genus are provided. For those genera where the type or a representative specimen is unavailable, a brief note is given. Altogether 174 genera of Pleosporales are treated. Phaeotrichaceae as well as Kriegeriella, Zeuctomorpha and Muroia are excluded from Pleosporales. Based on the multigene phylogenetic analysis, the suborder Massarineae is emended to accommodate five families, viz. Lentitheciaceae, Massarinaceae, Montagnulaceae, Morosphaeriaceae and Trematosphaeriaceae.
C1 [Hyde, Kevin D.] King Saud Univ, Coll Sci, Dept Bot & Microbiol, Riyadh 11442, Saudi Arabia.
[Zhang, Ying] Univ Hong Kong, Sch Biol Sci, Div Microbiol, Hong Kong, Hong Kong, Peoples R China.
[Crous, Pedro W.] CBS KNAW Fungal Biodivers Ctr, NL-3508 AD Utrecht, Netherlands.
[Schoch, Conrad L.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA.
[Hyde, Kevin D.] Mae Fah Luang Univ, Sch Sci, Muang 57100, Chiang Rai, Thailand.
RP Hyde, KD (reprint author), King Saud Univ, Coll Sci, Dept Bot & Microbiol, Riyadh 11442, Saudi Arabia.
EM kdhyde3@gmail.com
RI Crous, Pedro/H-1489-2012; Schoch, Conrad/J-4825-2012
OI Crous, Pedro/0000-0001-9085-8825;
FU Global Research Network; King Saud University
FX We are grateful to the Directors and Curators of the following herbaria
for loan of specimens in their keeping: BAFC, BISH, BPI, BR, BRIP, CBS,
E, ETH, FFE, FH, G, H, Herb. J. Kohlmeyer, HHUF, IFRD, ILLS, IMI, K(M),
L, LPS, M, MA, NY, PAD, PC, PH, RO, S, TNS, TRTC, UB, UBC, UPS and ZT;
to Dr. L. Cai, Dr. A. J. L. Phillips, Dr. C. Shearer and some other
mycologists for their permission to use or refer to their published
figures, to J. K. Liu, H. Zhang, Y.L. Yang and J. Fournier for helping
me loan or collect specimens, to H. Leung for technical help. The third
coauthor acknowledges the Intramural Research Program of the NIH,
National Library of Medicine. The Global Research Network and King Saud
University are also thanked for support.
NR 429
TC 252
Z9 259
U1 2
U2 50
PU SPRINGER
PI NEW YORK
PA 233 SPRING ST, NEW YORK, NY 10013 USA
SN 1560-2745
J9 FUNGAL DIVERS
JI Fungal Divers.
PD MAR
PY 2012
VL 53
IS 1
BP 1
EP 221
DI 10.1007/s13225-011-0117-x
PG 221
WC Mycology
SC Mycology
GA 896QB
UT WOS:000300583500001
PM 23097638
ER
PT J
AU Lakatta, EG
Maltsev, VA
AF Lakatta, Edward G.
Maltsev, Victor A.
TI Rebuttal: What I-f the shoe doesn't fit? "The funny current has a major
pacemaking role in the sinus node"
SO HEART RHYTHM
LA English
DT Editorial Material
C1 [Lakatta, Edward G.; Maltsev, Victor A.] NIA, Cardiovasc Sci Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA.
RP Lakatta, EG (reprint author), NIA, Cardiovasc Sci Lab, IRP, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA.
EM LakattaE@grc.nia.nih.gov
FU Intramural NIH HHS [Z01 AG000260-01]; NIA NIH HHS [Z01 AG000260-01]
NR 5
TC 6
Z9 6
U1 1
U2 6
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1547-5271
J9 HEART RHYTHM
JI Heart Rhythm
PD MAR
PY 2012
VL 9
IS 3
BP 459
EP 460
DI 10.1016/j.hrthm.2011.09.024
PG 2
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 898CJ
UT WOS:000300712700031
PM 21925131
ER
PT J
AU Zarember, KA
Marshall-Batty, KR
Cruz, AR
Chu, J
Fenster, ME
Shoffner, AR
Rogge, LS
Whitney, AR
Czapiga, M
Song, HH
Shaw, PA
Nagashima, K
Malech, HL
Deleo, FR
Holland, SM
Gallin, JI
Greenberg, DE
AF Zarember, Kol A.
Marshall-Batty, Kimberly R.
Cruz, Anna R.
Chu, Jessica
Fenster, Michael E.
Shoffner, Adam R.
Rogge, Larissa S.
Whitney, Adeline R.
Czapiga, Meggan
Song, Helen H.
Shaw, Pamela A.
Nagashima, Kunio
Malech, Harry L.
Deleo, Frank R.
Holland, Steven M.
Gallin, John I.
Greenberg, David E.
TI Innate Immunity against Granulibacter bethesdensis, an Emerging
Gram-Negative Bacterial Pathogen
SO INFECTION AND IMMUNITY
LA English
DT Article
ID HUMAN POLYMORPHONUCLEAR LEUKOCYTES; CHRONIC GRANULOMATOUS-DISEASE; HUMAN
NEUTROPHILS; PERITONEAL-DIALYSIS; SEQUENCE-ANALYSIS; ASAIA-BOGORENSIS;
APOPTOSIS; PATIENT; PHAGOCYTOSIS; BACTEREMIA
AB Acetic acid bacteria were previously considered nonpathogenic in humans. However, over the past decade, five genera of Acetobacteraceae have been isolated from patients with inborn or iatrogenic immunodeficiencies. Here, we describe the first studies of the interactions of the human innate immune system with a member of this bacterial family, Granulibacter bethesdensis, an emerging pathogen in patients with chronic granulomatous disease (CGD). Efficient phagocytosis of G. bethesdensis by normal and CGD polymorphonuclear leukocytes (CGD PMN) required heat-labile serum components (e.g., C3), and binding of C3 and C9 to G. bethesdensis was detected by immunoblotting. However, this organism survived in human serum concentrations of >= 90%, indicating a high degree of serum resistance. Consistent with the clinical host tropism of G. bethesdensis, CGD PMN were unable to kill this organism, while normal PMN, in the presence of serum, reduced the number of CFU by about 50% after a 24-h coculture. This finding, together with the observations that G. bethesdensis was sensitive to H2O2 but resistant to LL-37, a human cationic antimicrobial peptide, suggests an inherent resistance to O-2-independent killing. Interestingly, 10 to 100 times greater numbers of G. bethesdensis were required to achieve the same level of reactive oxygen species (ROS) production induced by Escherichia coli in normal PMN. In addition to the relative inability of the organism to elicit production of PMN ROS, G. bethesdensis inhibited both constitutive and FAS-induced PMN apoptosis. These properties of reduced PMN activation and resistance to nonoxidative killing mechanisms likely play an important role in G. bethesdensis pathogenesis.
C1 [Zarember, Kol A.; Cruz, Anna R.; Chu, Jessica; Rogge, Larissa S.; Song, Helen H.; Malech, Harry L.; Gallin, John I.] NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA.
[Marshall-Batty, Kimberly R.; Fenster, Michael E.; Shoffner, Adam R.; Holland, Steven M.; Greenberg, David E.] NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA.
[Marshall-Batty, Kimberly R.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA.
[Whitney, Adeline R.; Deleo, Frank R.] NIAID, Lab Human Bacterial Pathogenesis, NIH, Hamilton, MT USA.
[Czapiga, Meggan; Greenberg, David E.] NIAID, Res Technol Branch, NIH, Bethesda, MD 20892 USA.
[Shaw, Pamela A.] NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 USA.
[Nagashima, Kunio] SAIC Frederick Inc, Frederick, MD USA.
RP Zarember, KA (reprint author), NIAID, Host Def Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM kzarember@niaid.nih.gov; david.greenberg@utsouthwestern.edu
OI Malech, Harry/0000-0001-5874-5775; DeLeo, Frank/0000-0003-3150-2516;
Chu, Jessica/0000-0002-5763-873X
FU National Institute of Allergy and Infectious Diseases; NIH Clinical
Center; [HHSN26120080001E]
FX This work was supported in part by the Intramural Research Program of
the National Institute of Allergy and Infectious Diseases as well as the
NIH Clinical Center. K.N. is supported through contract
HHSN26120080001E.
NR 32
TC 8
Z9 8
U1 0
U2 2
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0019-9567
J9 INFECT IMMUN
JI Infect. Immun.
PD MAR
PY 2012
VL 80
IS 3
BP 975
EP 981
DI 10.1128/IAI.05557-11
PG 7
WC Immunology; Infectious Diseases
SC Immunology; Infectious Diseases
GA 897DA
UT WOS:000300621600010
PM 22184421
ER
PT J
AU Copeland-Linder, N
Johnson, SB
Haynie, DL
Chung, SE
Cheng, TL
AF Copeland-Linder, Nikeea
Johnson, Sara B.
Haynie, Denise L.
Chung, Shang-en
Cheng, Tina L.
TI Retaliatory Attitudes and Violent Behaviors Among Assault-Injured Youth
SO JOURNAL OF ADOLESCENT HEALTH
LA English
DT Article
DE Youth violence; Assault injury; Adolescents; Violent behavior
ID AFRICAN-AMERICAN ADOLESCENTS; AGGRESSIVE-BEHAVIOR; ANTISOCIAL-BEHAVIOR;
PREVENTION; VICTIMIZATION; STUDENTS
AB Objectives: To examine the effect of retaliatory attitudes on subsequent violent behavior and fight-related injuries among youth who presented to the emergency department with assault injuries.
Design: Assault-injured youth were interviewed at baseline, 6 months, and 18 months to assess fighting behavior, retaliatory attitudes, weapon carrying, and injury history as part of a larger randomized control trial.
Setting: Two emergency departments in urban areas were selected for the study.
Participants: A total of 129 adolescents aged 10-15 years were included in the study.
Outcome measures: Fighting behavior, assault injury, weapon carrying, and aggressive behavior.
Results: Higher retaliatory attitudes at baseline were associated with more aggression and a higher frequency of fighting over time.
Conclusions: Retaliatory attitudes may fuel cycles of violence among youth. Medical professionals in acute care settings have an opportunity to identify youths at risk of future assault injury by assessing retaliation, providing anticipatory guidance, and referring to intervention programs. (C) 2012 Society for Adolescent Health and Medicine. All rights reserved.
C1 [Copeland-Linder, Nikeea; Johnson, Sara B.; Chung, Shang-en; Cheng, Tina L.] Johns Hopkins Univ, Dept Pediat, Baltimore, MD 21231 USA.
[Johnson, Sara B.; Cheng, Tina L.] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Populat Family & Reprod Hlth, Baltimore, MD USA.
[Haynie, Denise L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Div Epidemiol Stat & Prevent, Bethesda, MD USA.
RP Copeland-Linder, N (reprint author), Johns Hopkins Univ, Dept Pediat, 1750 E Fairmount Ave, Baltimore, MD 21231 USA.
EM nlinder@ssw.umaryland.edu
OI Haynie, Denise/0000-0002-8270-6079
FU Eunice Kennedy Shriver National Institute of Child Health and Human
Development [1K24HD052559]; Maternal and Child Health Bureau, Health
Resources and Services Administration, Department of Health and Human
Services [R40MC00174, 4H34MC00025]; DC-Baltimore Research Center on
Child Health Disparities from the National Center on Minority Health and
Health Disparities [P20 MD00165, 00198]
FX This project was supported by the Intramural Research Program of the
Eunice Kennedy Shriver National Institute of Child Health and Human
Development (to D. L. H.), 1K24HD052559 (T. L. C.), the Maternal and
Child Health Bureau (Title V Social Security Act), Health Resources and
Services Administration, Department of Health and Human Services,
R40MC00174, 4H34MC00025 (T. L. C.), the DC-Baltimore Research Center on
Child Health Disparities grant number P20 MD00165 and 00198 from the
National Center on Minority Health and Health Disparities (T. L. C., N.
L.).
NR 31
TC 11
Z9 12
U1 3
U2 6
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1054-139X
J9 J ADOLESCENT HEALTH
JI J. Adolesc. Health
PD MAR
PY 2012
VL 50
IS 3
BP 215
EP 220
DI 10.1016/j.jadohealth.2011.04.005
PG 6
WC Psychology, Developmental; Public, Environmental & Occupational Health;
Pediatrics
SC Psychology; Public, Environmental & Occupational Health; Pediatrics
GA 897AK
UT WOS:000300612800002
PM 22325125
ER
PT J
AU Dempsey, AG
MacDonell, KE
Naar-King, S
Lau, CY
AF Dempsey, Allison G.
MacDonell, Karen E.
Naar-King, Sylvie
Lau, Chuen-Yen
CA Adolescent Med Trials Network HIV
TI Patterns of Disclosure Among Youth Who Are HIV-Positive: A Multisite
Study
SO JOURNAL OF ADOLESCENT HEALTH
LA English
DT Article
DE Serostatus disclosure; HIV/AIDS; Public health; Prevention/control
ID TRANSMISSION RISK; SEXUAL-BEHAVIOR; SELF-EFFICACY; ADOLESCENTS
AB Purpose: Disclosure of serostatus is critical in preventing the transmission of HIV among youth. The purpose of this exploratory study was to describe serostatus disclosure in a multisite study of youth living with HIV.
Methods: This study investigated serostatus disclosure and its relationship to unprotected sex among 146 youth participating in a multisite study of young people living with HIV who were sexually active within the past 3 months.
Results: Forty percent of participants reported a sexual relationship with a partner to whom they had not disclosed their serostatus. Participants with multiple sexual partners were less likely to disclose their serostatus than those with one partner. Disclosure was more frequent when the serostatus of the sexual partner was known. Disclosure was not associated with unprotected sex.
Conclusions: Prevention initiatives should focus on both disclosure and condom use in this high-risk population, particularly for youth with multiple sexual partners. (C) 2012 Society for Adolescent Health and Medicine. All rights reserved.
C1 [Dempsey, Allison G.] Univ Houston, Dept Educ Psychol, Houston, TX 77204 USA.
[MacDonell, Karen E.; Naar-King, Sylvie] Wayne State Univ, Dept Pediat, Pediat Prevent Res Ctr, Detroit, MI 48202 USA.
[Lau, Chuen-Yen] NIAID, Collaborat Clin Res Branch, Div Clin Res, NIH, Bethesda, MD 20892 USA.
RP Dempsey, AG (reprint author), Univ Houston, Dept Educ Psychol, 491 Farish Hall, Houston, TX 77204 USA.
EM agdempsey@uh.edu
RI Ghartouchent, malek/B-9088-2012
FU NICHD NIH HHS [5 U01 HD 40474, 5 U01-HD040533, U01 HD040474, U01
HD040533, U01 HD040533-01, U01 HD040533-10]
NR 9
TC 13
Z9 13
U1 1
U2 4
PU ELSEVIER SCIENCE INC
PI NEW YORK
PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA
SN 1054-139X
J9 J ADOLESCENT HEALTH
JI J. Adolesc. Health
PD MAR
PY 2012
VL 50
IS 3
BP 315
EP 317
DI 10.1016/j.jadohealth.2011.06.003
PG 3
WC Psychology, Developmental; Public, Environmental & Occupational Health;
Pediatrics
SC Psychology; Public, Environmental & Occupational Health; Pediatrics
GA 897AK
UT WOS:000300612800017
PM 22325140
ER
PT J
AU Takeuchi, N
Wolf, YI
Makarova, KS
Koonin, EV
AF Takeuchi, Nobuto
Wolf, Yuri I.
Makarova, Kira S.
Koonin, Eugene V.
TI Nature and Intensity of Selection Pressure on CRISPR-Associated Genes
SO JOURNAL OF BACTERIOLOGY
LA English
DT Article
ID IMMUNE-SYSTEM; ANTAGONISTIC COEVOLUTION; RECOMBINANT SEQUENCES;
PROKARYOTIC GENOMES; ACQUIRED-RESISTANCE; HORIZONTAL TRANSFER;
MAXIMUM-LIKELIHOOD; ANTIVIRAL DEFENSE; PROTEIN FAMILIES; MOSAIC
STRUCTURE
AB The recently discovered CRISPR-Cas adaptive immune system is present in almost all archaea and many bacteria. It consists of cassettes of CRISPR repeats that incorporate spacers homologous to fragments of viral or plasmid genomes that are employed as guide RNAs in the immune response, along with numerous CRISPR-associated (cas) genes that encode proteins possessing diverse, only partially characterized activities required for the action of the system. Here, we investigate the evolution of the cas genes and show that they evolve under purifying selection that is typically much weaker than the median strength of purifying selection affecting genes in the respective genomes. The exceptions are the cas1 and cas2 genes that typically evolve at levels of purifying selection close to the genomic median. Thus, although these genes are implicated in the acquisition of spacers from alien genomes, they do not appear to be directly involved in an arms race between bacterial and archaeal hosts and infectious agents. These genes might possess functions distinct from and additional to their role in the CRISPR-Cas-mediated immune response. Taken together with evidence of the frequent horizontal transfer of cas genes reported previously and with the wide-spread microscale recombination within these genes detected in this work, these findings reveal the highly dynamic evolution of cas genes. This conclusion is in line with the involvement of CRISPR-Cas in antiviral immunity that is likely to entail a coevolutionary arms race with rapidly evolving viruses. However, we failed to detect evidence of strong positive selection in any of the cas genes.
C1 [Takeuchi, Nobuto; Wolf, Yuri I.; Makarova, Kira S.; Koonin, Eugene V.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA.
RP Koonin, EV (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA.
EM koonin@ncbi.nlm.nih.gov
FU NIH, National Library of Medicine
FX This research was supported by the Intramural Research Program of the
NIH, National Library of Medicine.
NR 68
TC 31
Z9 31
U1 2
U2 9
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0021-9193
J9 J BACTERIOL
JI J. Bacteriol.
PD MAR
PY 2012
VL 194
IS 5
BP 1216
EP 1225
DI 10.1128/JB.06521-11
PG 10
WC Microbiology
SC Microbiology
GA 895XU
UT WOS:000300530800033
PM 22178975
ER
PT J
AU Prado, MAM
Baron, G
AF Prado, Marco A. M.
Baron, Gerald
TI Seeding plaques in Alzheimer's disease
SO JOURNAL OF NEUROCHEMISTRY
LA English
DT Editorial Material
ID AMYLOID PRECURSOR PROTEIN; CEREBRAL BETA-AMYLOIDOSIS; DEPOSITION;
INDUCTION; MODEL
C1 [Prado, Marco A. M.] Univ Western Ontario, Schulich Sch Med & Dent, Dept Anat & Cell Biol, Robarts Res Inst,Dept Physiol & Pharmacol, London, ON, Canada.
[Baron, Gerald] NIAID, NIH, Persistent Viral Dis Lab, Rocky Mt Labs, Hamilton, MT USA.
RP Prado, MAM (reprint author), Univ Western Ontario, Schulich Sch Med & Dent, Dept Anat & Cell Biol, Robarts Res Inst,Dept Physiol & Pharmacol, London, ON, Canada.
EM mprado@robarts.ca
RI Prado, Marco/K-7638-2013
OI Prado, Marco/0000-0002-3028-5778
FU Canadian Institutes of Health Research; Intramural NIH HHS [ZIA
AI000982-07]
NR 18
TC 4
Z9 4
U1 0
U2 0
PU WILEY-BLACKWELL
PI MALDEN
PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA
SN 0022-3042
J9 J NEUROCHEM
JI J. Neurochem.
PD MAR
PY 2012
VL 120
IS 5
BP 641
EP 643
DI 10.1111/j.1471-4159.2011.07574.x
PG 3
WC Biochemistry & Molecular Biology; Neurosciences
SC Biochemistry & Molecular Biology; Neurosciences & Neurology
GA 895NQ
UT WOS:000300503400001
PM 22050472
ER
PT J
AU McBryde, KD
AF McBryde, Kevin D.
TI Blood Pressure in Pediatric Chronic Kidney Disease-It's in the Ears of
the Beholder
SO JOURNAL OF PEDIATRICS
LA English
DT Editorial Material
ID CHILDREN; AGREEMENT
C1 NIDDK, Off Minor Hlth Res Coordinat, NIH, Bethesda, MD 20892 USA.
RP McBryde, KD (reprint author), NIDDK, Off Minor Hlth Res Coordinat, NIH, 6707 Democracy Blvd,2 Democracy Plaza,Room 906B, Bethesda, MD 20892 USA.
EM kevin.mcbryde@nih.gov
NR 15
TC 1
Z9 1
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-3476
J9 J PEDIATR-US
JI J. Pediatr.
PD MAR
PY 2012
VL 160
IS 3
BP 363
EP 365
DI 10.1016/j.jpeds.2011.10.004
PG 3
WC Pediatrics
SC Pediatrics
GA 897AT
UT WOS:000300613700004
PM 22082951
ER
PT J
AU O'Shea, TM
Allred, EN
Kuban, KCK
Dammann, O
Paneth, N
Fichorova, R
Hirtz, D
Leviton, A
AF O'Shea, T. Michael
Allred, Elizabeth N.
Kuban, Karl C. K.
Dammann, Olaf
Paneth, Nigel
Fichorova, Raina
Hirtz, Deborah
Leviton, Alan
CA Extremely Low Gestational Age
TI Elevated Concentrations of Inflammation-Related Proteins in Postnatal
Blood Predict Severe Developmental Delay at 2 Years of Age in Extremely
Preterm Infants
SO JOURNAL OF PEDIATRICS
LA English
DT Article
ID WHITE-MATTER ABNORMALITIES; NECROTIZING ENTEROCOLITIS; CEREBRAL-PALSY;
BRAIN-DAMAGE; CHILDREN; CHORIOAMNIONITIS; NEWBORNS; OUTCOMES; MARKERS;
BIRTH
AB Objective To evaluate the hypothesis that elevated levels of inflammation-related proteins in early postnatal blood predict impaired mental and motor development in extremely preterm infants.
Study design We measured concentrations of 25 inflammation-related proteins in blood collected on postnatal days 1, 7, and 14 from 939 infants born before 28 weeks gestation. An elevated level was defined as a concentration in the highest quartile for gestational age and day of blood collection. We identified impaired development at age 24 months using the Bayley Scales of Infant Development, Second Edition. The primary outcomes were scores on the Mental Scale or the Motor Scale of <55 (more than 3 SDs below the mean).
Results For 17 of the 25 inflammation-related proteins, 1 or more statistically significant associations (P < .01) was found between an elevated blood level of the protein and a developmental impairment. Elevations on multiple days were more often associated with developmental impairment than were elevations present for only 1 day. The highest number of predictive elevations was found in day-14 blood.
Conclusion In extremely preterm infants, elevated levels of inflammation-related proteins in blood collected on postnatal days 7 and 14, especially when sustained, are associated with impaired mental and motor development at age 2 years. (J Pediatr 2012; 160:395-401).
C1 [O'Shea, T. Michael] Wake Forest Univ, Bowman Gray Sch Med, Dept Pediat, Winston Salem, NC 27157 USA.
[Allred, Elizabeth N.; Fichorova, Raina; Leviton, Alan] Harvard Univ, Sch Med, Cambridge, MA 02138 USA.
[Allred, Elizabeth N.] Harvard Univ, Sch Publ Hlth, Cambridge, MA 02138 USA.
[Kuban, Karl C. K.] Boston Med Ctr, Dept Pediat, Boston, MA USA.
[Paneth, Nigel] Michigan State Univ, Dept Epidemiol, E Lansing, MI 48824 USA.
[Fichorova, Raina] Brigham & Womens Hosp, Dept Obstet Gynecol & Reprod Biol, Boston, MA 02115 USA.
[Hirtz, Deborah] NINDS, Bethesda, MD 20892 USA.
RP O'Shea, TM (reprint author), Wake Forest Univ, Bowman Gray Sch Med, Dept Pediat, 300 S Hawthorne Rd, Winston Salem, NC 27157 USA.
EM moshea@wfubmc.edu
RI Fichorova, Raina/G-9969-2014;
OI Kuban, Karl/0000-0001-5299-3567
FU National Institute of Neurological Disorders and Stroke [NS 40069]
FX Supported by the National Institute of Neurological Disorders and Stroke
(Grant NS 40069). This study was completed as a cooperative agreement
with the National Institute of Neurological Disorders and Stroke. The
study sponsor participated in the study design, but not in the data
collection or data analysis. The authors declare no conflicts of
interest.
NR 29
TC 35
Z9 38
U1 0
U2 6
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-3476
J9 J PEDIATR-US
JI J. Pediatr.
PD MAR
PY 2012
VL 160
IS 3
BP 395
EP 401
DI 10.1016/j.jpeds.2011.08.069
PG 7
WC Pediatrics
SC Pediatrics
GA 897AT
UT WOS:000300613700011
PM 22000304
ER
PT J
AU Higgins, RD
Devaskar, S
Hay, WW
Ehrenkranz, RA
Greer, FR
Kennedy, K
Meier, P
Papile, L
Sherman, MP
AF Higgins, Rosemary D.
Devaskar, Sherin
Hay, William W., Jr.
Ehrenkranz, Richard A.
Greer, Frank R.
Kennedy, Kathleen
Meier, Paula
Papile, LuAnn
Sherman, Michael P.
TI Executive Summary of the Workshop "Nutritional Challenges in the High
Risk Infant"
SO JOURNAL OF PEDIATRICS
LA English
DT Article
ID BIRTH-WEIGHT INFANTS; EPIDERMAL-GROWTH-FACTOR; INTENSIVE-CARE-UNIT;
PREVENT NECROTIZING ENTEROCOLITIS; BREAST-MILK; PRETERM INFANTS;
DEVELOPMENTAL ORIGINS; GESTATIONAL-AGE; NEONATAL-RATS; ADULT DISEASE
C1 [Higgins, Rosemary D.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pregnancy & Perinatol Branch, Ctr Dev Biol & Perinatal Med, NIH, Bethesda, MD 20892 USA.
[Devaskar, Sherin] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pediat, Los Angeles, CA 90095 USA.
[Hay, William W., Jr.] Univ Colorado, Sch Med, Dept Pediat, Aurora, CO USA.
[Ehrenkranz, Richard A.] Yale Univ, Sch Med, Dept Pediat, New Haven, CT 06510 USA.
[Greer, Frank R.] Univ Wisconsin, Dept Pediat, Madison, WI USA.
[Kennedy, Kathleen] Univ Texas Houston, Sch Med, Div Neonatal Perinatal Med, Houston, TX USA.
[Meier, Paula] Rush Univ, Med Ctr, Dept Women Children & Family Nursing, Chicago, IL 60612 USA.
[Meier, Paula] Rush Univ, Med Ctr, Dept Pediat, Chicago, IL 60612 USA.
[Papile, LuAnn] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA.
[Sherman, Michael P.] Univ Missouri, Dept Child Hlth, Columbia, MO 65201 USA.
RP Higgins, RD (reprint author), Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pregnancy & Perinatol Branch, Ctr Dev Biol & Perinatal Med, NIH, 6100 Execut Blvd,Room 4B03,MSC 7510, Bethesda, MD 20892 USA.
EM higginsr@mail.nih.gov
FU Office of Rare Disease and National Institutes of Health
FX This workshop was co-funded by the Office of Rare Disease and National
Institutes of Health. The authors declare no conflicts of interest.
NR 40
TC 5
Z9 5
U1 1
U2 2
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-3476
J9 J PEDIATR-US
JI J. Pediatr.
PD MAR
PY 2012
VL 160
IS 3
BP 511
EP 516
DI 10.1016/j.jpeds.2011.12.024
PG 6
WC Pediatrics
SC Pediatrics
GA 897AT
UT WOS:000300613700033
PM 22240111
ER
PT J
AU Arabshahi, B
Silverman, RA
Jones, OY
Rider, LG
AF Arabshahi, Bita
Silverman, Robert A.
Jones, Olcay Y.
Rider, Lisa G.
TI Abatacept and Sodium Thiosulfate for Treatment of Recalcitrant Juvenile
Dermatomyositis Complicated by Ulceration and Calcinosis
SO JOURNAL OF PEDIATRICS
LA English
DT Article
ID RHEUMATOID-ARTHRITIS
AB We report the successful use of abatacept and sodium thiosulfate in a patient with severe recalcitrant juvenile dermatomyositis complicated by ulcerative skin disease and progressive calcinosis. This combination therapy resulted in significant reductions in muscle and skin inflammation, decreased corticosteroid dependence, and halted the progression of calcinosis. (J Pediatr 2012;160:520-2)
C1 [Arabshahi, Bita] Inova Fairfax Hosp Children, Div Pediat Rheumatol, Dept Pediat, Fairfax, VA USA.
[Silverman, Robert A.] Georgetown Univ, Dept Pediat, Washington, DC 20057 USA.
[Jones, Olcay Y.] Walter Reed Army Med Ctr, Dept Pediat, Div Pediat Rheumatol, Washington, DC 20307 USA.
[Jones, Olcay Y.; Rider, Lisa G.] George Washington Univ, Dept Med, Ctr Myositis, Washington, DC USA.
[Rider, Lisa G.] Natl Inst Environm Hlth Sci, Environm Autoimmun Grp, Program Clin Res, NIH,US Dept HHS, Bethesda, MD USA.
RP Arabshahi, B (reprint author), Inova Fairfax Pediat Subspecialty Ctr, 8505 Arlington Blvd,Suite 100, Fairfax, VA 22031 USA.
EM bita.arabshahi@inova.org
OI Rider, Lisa/0000-0002-6912-2458
FU National Institute of Environmental Health Sciences, National Institutes
of Health; Cure JM Foundation; Inova Fairfax Hospital for Children,
Inova Health System Foundation
FX Supported by the intramural research program of the National Institute
of Environmental Health Sciences, National Institutes of Health; the
Cure JM Foundation; and the Mohsen Ziai, MD Pediatric Endowment at Inova
Fairfax Hospital for Children, Inova Health System Foundation. The views
expressed in this article are those of the authors and do not
necessarily reflect the official policy or position of the Department of
Defense or the US Government. The authors declare no conflicts of
interest.
NR 11
TC 30
Z9 32
U1 0
U2 0
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0022-3476
J9 J PEDIATR-US
JI J. Pediatr.
PD MAR
PY 2012
VL 160
IS 3
BP 520
EP 522
DI 10.1016/j.jpeds.2011.11.057
PG 3
WC Pediatrics
SC Pediatrics
GA 897AT
UT WOS:000300613700035
PM 22244459
ER
PT J
AU Negus, SS
O'Connell, R
Morrissey, E
Cheng, KJ
Rice, KC
AF Negus, S. Stevens
O'Connell, Robert
Morrissey, Ember
Cheng, Kejun
Rice, Kenner C.
TI Effects of Peripherally Restricted kappa Opioid Receptor Agonists on
Pain-Related Stimulation and Depression of Behavior in Rats
SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
LA English
DT Article
ID IRRITABLE-BOWEL-SYNDROME; SALVINORIN-A; ANALGESIC EFFICACY; PRECLINICAL
ASSAYS; SALVIA-DIVINORUM; SELF-STIMULATION; ASIMADOLINE; MICE;
ICI-204448; ENADOLINE
AB kappa Opioid receptor agonists that do not readily cross the blood-brain barrier are peripherally restricted and distribute poorly to the central nervous system after systemic administration. Peripherally restricted kappa agonists have promise as candidate analgesics, because they may produce antinociception mediated by peripheral kappa receptors more potently than they produce undesirable sedative and psychotomimetic effects mediated by central kappa receptors. The present study used assays of pain-related stimulation and depression of behavior in rats to compare effects of 1) two peripherally restricted kappa agonists [the tetrapeptide D-Phe-D-Phe-D-Ile-D-Arg-NH2 (ffir) and the nonpeptidic compound ((R, S)-N-[2-(N-methyl-3,4-dichlorophenylacetamido)-2-(3-carboxyphenyl)-ethyl]pyrrolidine hydrochloride (ICI204448)], 2) a centrally penetrating kappa agonist (salvinorin A), and 3) several reference drugs, including a nonsteroidal anti-inflammatory drug (NSAID; ketoprofen). Intraperitoneal injection of dilute lactic acid served as a noxious stimulus to stimulate a stretching response and depress intracranial self-stimulation (ICSS) maintained by the delivery of electrical brain stimulation to the medial forebrain bundle. Acid-stimulated stretching was blocked by ketoprofen, the peripherally restricted kappa agonists, and salvinorin A. However, acid-induced depression of ICSS was blocked only by ketoprofen. The peripherally restricted kappa agonists had little effect, and salvinorin A exacerbated acid-induced depression of ICSS. These results suggest that peripherally restricted kappa agonists may be safer than centrally penetrating kappa agonists but less efficacious than NSAIDS or kappa opioid receptor agonists to block pain-related depression of behavior; however, the peripheral selectivity of ffir and ICI204448 is limited, and future studies with kappa agonists capable of greater peripheral selectivity are warranted.
C1 [Negus, S. Stevens; O'Connell, Robert; Morrissey, Ember] Virginia Commonwealth Univ, Dept Pharmacol & Toxicol, Richmond, VA 23220 USA.
[Cheng, Kejun; Rice, Kenner C.] Natl Inst Drug Abuse, Biol Res Branch, Bethesda, MD USA.
[Cheng, Kejun; Rice, Kenner C.] NIAAA, Bethesda, MD USA.
RP Negus, SS (reprint author), Virginia Commonwealth Univ, Dept Pharmacol & Toxicol, 410 N 12th St, Richmond, VA 23220 USA.
EM ssnegus@vcu.edu
FU National Institutes of Health National Institute on Drug Abuse
[R01-DA11460]; National Institutes of Health National Institute of
Neurological Disorders and Stroke [R01-NS070715]; National Institute on
Drug Abuse; National Institute on Alcohol Abuse and Alcoholism
FX This work was supported in part by the National Institutes of Health
National Institute on Drug Abuse [Grant R01-DA11460]; the National
Institutes of Health National Institute of Neurological Disorders and
Stroke [Grant R01-NS070715]; and the Intramural Research Programs of the
National Institute on Drug Abuse and the National Institute on Alcohol
Abuse and Alcoholism.
NR 41
TC 23
Z9 23
U1 1
U2 9
PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
PI BETHESDA
PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA
SN 0022-3565
J9 J PHARMACOL EXP THER
JI J. Pharmacol. Exp. Ther.
PD MAR
PY 2012
VL 340
IS 3
BP 501
EP 509
DI 10.1124/jpet.111.186783
PG 9
WC Pharmacology & Pharmacy
SC Pharmacology & Pharmacy
GA 897CL
UT WOS:000300619000002
PM 22128346
ER
PT J
AU Hogg, ME
Vavra, AK
Banerjee, MN
Martinez, J
Jiang, Q
Keefer, LK
Chambon, P
Kibbe, MR
AF Hogg, Melissa E.
Vavra, Ashley K.
Banerjee, Monisha N.
Martinez, Janet
Jiang, Qun
Keefer, Larry K.
Chambon, Pierre
Kibbe, Melina R.
TI The Role of Estrogen Receptor alpha and beta in Regulating Vascular
Smooth Muscle Cell Proliferation is Based on Sex
SO JOURNAL OF SURGICAL RESEARCH
LA English
DT Article
DE neointimal hyperplasia; vascular smooth muscle; nitric oxide; hormones;
estrogen receptors
ID NITRIC-OXIDE SYNTHASE; PRECURSOR L-ARGININE; RAT CAROTID-ARTERY; INTIMAL
HYPERPLASIA; NEOINTIMA FORMATION; INJURY RESPONSE; PERIVASCULAR
DELIVERY; DEFICIENT MICE; KNOCKOUT MICE; GENE-TRANSFER
AB Background. We previously demonstrated that vascular smooth muscle cells (VSMC) proliferation and development of neointimal hyperplasia as well as the ability of nitric oxide (NO) to inhibit these processes is dependent on sex and hormone status. The aim of this study was to evaluate the role of estrogen receptor (ER) in mediating proliferation in male and female VSMC.
Materials and Methods. Proliferation was assessed in primary rat aortic male and female VSMC using 3 H-thymidine incorporation in the presence or absence of ER alpha (alpha) inhibitor methyl-piperidinopyrazole, the ER beta (beta) inhibitor (R, R)-5,11-Diethyl-5,6,11,12- tetrahydro-2,8-chrysenediol, the combined ER alpha beta inhibitor ICI 182,780, and/or the NO donor DETA/NO. Proliferation was also assessed in primary aortic mouse VSMC harvested from wildtype (WT), ER alpha knockout (ER alpha KO), and ER beta knockout (ER beta KO) mice in the presence or absence of DETA/NO and the ER alpha, ER beta, and ER alpha beta inhibitors. Protein levels were assessed using Western blot analysis.
Results. Protein expression of ER alpha and ER beta was present and equal in male and female VSMC, and did not change after exposure to NO. Inhibition of either ER alpha or ER beta had no effect on VSMC proliferation in the presence or absence of NO in either sex. However, inhibition of ER alpha beta in rat VSMC mitigated NO-mediated inhibition in female but not male VSMC (P<0.05). Evaluation of proliferation in the knockout mice revealed distinct patterns. Male ER alpha KO and ER beta KO VSMC proliferated faster than male WT VSMC (P < 0.05). Female ER beta KO proliferated faster than female WT VSMC (P < 0.05), but female ER alpha KO VSMC proliferated slower than female WT VSMC (P<0.05). Last, we evaluated the effect of combined inhibition of ER alpha and ER beta in these knockout strains. Combined ER alpha beta inhibition abrogated NO-mediated inhibition of VSMC proliferation in female WT and knockout VSMC (P<0.05), but not in male VSMC.
Conclusions. These data clearly demonstrate a role for the ER in mediating VSMC proliferation in both sexes. However, these data suggest that the antiproliferative effects of NO may be regulated by the ER in females but not males. Published by Elsevier Inc.
C1 [Kibbe, Melina R.] Northwestern Univ, Div Vasc Surg, Inst BioNanotechnol Med, Chicago, IL 60611 USA.
[Hogg, Melissa E.; Vavra, Ashley K.; Banerjee, Monisha N.; Martinez, Janet; Jiang, Qun; Kibbe, Melina R.] Northwestern Univ, Feinberg Sch Med, Div Vasc Surg, Chicago, IL 60611 USA.
[Keefer, Larry K.] NCI, Comparat Carcinogenesis Lab, Frederick, MD 21701 USA.
[Chambon, Pierre] CU, Inst Genet & Biol Mol & Cellulaire, Illkirch Graffenstaden, De Strasbourg, France.
RP Kibbe, MR (reprint author), Northwestern Univ, Div Vasc Surg, Inst BioNanotechnol Med, 676 N St Clair St,650, Chicago, IL 60611 USA.
EM mkibbe@nmh.org
RI Keefer, Larry/N-3247-2014
OI Keefer, Larry/0000-0001-7489-9555
FU Intramural NIH HHS; NCI NIH HHS [N01CO12400]; NCRR NIH HHS [UL1
RR025741]; NHLBI NIH HHS [K08 HL084203-05, K08HL084203, K08 HL084203]
NR 42
TC 7
Z9 8
U1 1
U2 2
PU ACADEMIC PRESS INC ELSEVIER SCIENCE
PI SAN DIEGO
PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
SN 0022-4804
EI 1095-8673
J9 J SURG RES
JI J. Surg. Res.
PD MAR
PY 2012
VL 173
IS 1
BP E1
EP E10
DI 10.1016/j.jss.2011.09.021
PG 10
WC Surgery
SC Surgery
GA 897AH
UT WOS:000300612500001
PM 22099601
ER
PT J
AU Oh, JK
Pellikka, PA
Panza, JA
Biernat, J
Attisano, T
Manahan, BG
Wiste, HJ
Lin, G
Lee, K
Miller, FA
Stevens, S
Sopko, G
She, LL
Velazquez, EJ
AF Oh, Jae K.
Pellikka, Patricia A.
Panza, Julio A.
Biernat, Jolanta
Attisano, Tiziana
Manahan, Barbara G.
Wiste, Heather J.
Lin, Grace
Lee, Kerry
Miller, Fletcher A.
Stevens, Susanna
Sopko, George
She, Lilin
Velazquez, Eric J.
CA STICH Trial Investigators
TI Core Lab Analysis of Baseline Echocardiographic Studies in the STICH
Trial and Recommendation for Use of Echocardiography in Future Clinical
Trials
SO JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY
LA English
DT Article
DE Ischemic; Cardiomyopathy; Echocardiography
ID VENTRICULAR DIASTOLIC DYSFUNCTION; FUNCTIONAL MITRAL REGURGITATION;
INFERIOR VENA-CAVA; HEART-FAILURE; AMERICAN-SOCIETY; DILATED
CARDIOMYOPATHY; MYOCARDIAL-INFARCTION; STANDARDS COMMITTEE;
OF-ECHOCARDIOGRAPHY; MAJOR DETERMINANT
AB Background: The Surgical Treatment for Ischemic Heart Failure (STICH) randomized trial was designed to identify an optimal management strategy for patients with ischemic cardiomyopathy. Baseline echocardiographic examinations were required for all patients. The primary aim of this report is to describe the baseline STICH Echocardiography Core Laboratory data. The secondary aim is to provide recommendations regarding how echocardiography should be used in clinical practice and research on the basis of the experience gained from echocardiography in STICH.
Methods: Between September 2002 and January 2006, 2,136 patients with ejection fractions (EFs)<= 35% and coronary artery disease amenable to coronary artery bypass grafting were enrolled. Echocardiography was acquired by 122 clinical enrolling sites, and measurements were performed by the Echocardiography Core Laboratory after a certification process for all clinical sites.
Results: Echocardiography was available for analysis in 2,006 patients (93.9%); 1,734 (86.4%) were men, and the mean age was 60.9 +/- 9.5 years. The mean left ventricular end-systolic volume index, measureable in 72.8%, was 84.0 +/- 30.9 mL/m(2), and the mean EF was 28.9 +/- 8.3%, with 18.5% of patients having EFs > 35%. Single-plane measurements of left ventricular and left atrial volumes were similar to their volumes by biplane measurement (r = 0.97 and r = 0.92, respectively). Mitral regurgitation severity by visual assessment was associated with a wide range of effective regurgitant orifice area, while effective regurgitant orifice area >= 0.2 cm(2) indicated at least moderate mitral regurgitation by visual assessment. Deceleration time of mitral inflow velocity had a weak correlation with EF (r = 0.25) but was inversely related to estimated pulmonary artery systolic pressure (r = -0.49).
Conclusions: In STICH patients with ischemic cardiomyopathy, Echocardiography Core Laboratory analysis of baseline echocardiographic findings demonstrated a wide spectrum of left ventricular shape, function, and hemodynamics, as well as the feasibility and limitations of obtaining essential echocardiographic measurements. It is critical that the use of echocardiographic parameters in clinical practice and research balance the strengths and weaknesses of the technique. (J Am Soc Echocardiogr 2012;25:327-36.)
C1 [Oh, Jae K.; Pellikka, Patricia A.; Manahan, Barbara G.; Wiste, Heather J.; Lin, Grace; Miller, Fletcher A.] Mayo Clin, Div Cardiovasc Dis, Echocardiog Core Lab, Rochester, MN 55905 USA.
[Panza, Julio A.] Washington Hosp Ctr, Dept Med Cardiovasc Dis, Washington, DC 20010 USA.
[Biernat, Jolanta] Med Univ Silesia, Katowich, Poland.
[Attisano, Tiziana] DAragona Hosp, Salemo, Italy.
[Lee, Kerry; Stevens, Susanna; She, Lilin] Data Coordinating Ctr STICH, Duke Clin Res Inst, Durham, NC USA.
[Sopko, George] NHLBI, Div Cardiovasc Sci, Bethesda, MD 20892 USA.
[Velazquez, Eric J.] Duke Univ, Div Cardiovasc Med, Duke Clin Res Inst, Durham, NC USA.
RP Oh, JK (reprint author), Mayo Clin, Div Cardiovasc Dis, Echocardiog Core Lab, 200 1st St SW, Rochester, MN 55905 USA.
EM oh.jae@mayo.edu
FU National Institutes of Health (Bethesda, MD) [UO5-HL-69010]
FX This study was supported by grant UO5-HL-69010 from the National
Institutes of Health (Bethesda, MD).
NR 38
TC 25
Z9 26
U1 0
U2 2
PU MOSBY-ELSEVIER
PI NEW YORK
PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA
SN 0894-7317
J9 J AM SOC ECHOCARDIOG
JI J. Am. Soc. Echocardiogr.
PD MAR
PY 2012
VL 25
IS 3
BP 327
EP 336
DI 10.1016/j.echo.2011.12.002
PG 10
WC Cardiac & Cardiovascular Systems
SC Cardiovascular System & Cardiology
GA 897FW
UT WOS:000300633200015
PM 22227341
ER
PT J
AU Majeed, F
Kamal, AK
AF Majeed, Farzin
Kamal, Ayeesha Kamran
TI Can community based interventions control hypertension in developing
countries? What is the evidence from Pakistan?
SO JOURNAL OF THE PAKISTAN MEDICAL ASSOCIATION
LA English
DT Editorial Material
ID BLOOD-PRESSURE
C1 [Majeed, Farzin] Aga Khan Univ Hosp, Stroke Serv, Karachi, Pakistan.
Aga Khan Univ Hosp, Natl Inst Neurol Disorders & Stroke, Karachi, Pakistan.
Aga Khan Univ Hosp, Int Cerebrovasc Translat Clin Res Training Progra, Vasc Fellowship Program, Fogarty Int Ctr, Karachi, Pakistan.
RP Majeed, F (reprint author), Aga Khan Univ Hosp, Stroke Serv, Karachi, Pakistan.
FU FIC NIH HHS [D43TW008660, D43 TW008660]
NR 3
TC 0
Z9 0
U1 0
U2 1
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 MAR
PY 2012
VL 62
IS 3
BP 301
EP 302
PG 2
WC Medicine, General & Internal; Medicine, Research & Experimental
SC General & Internal Medicine; Research & Experimental Medicine
GA 892HJ
UT WOS:000300277000030
PM 22764475
ER
PT J
AU Mazurov, D
Ilinskaya, A
Heidecker, G
Filatov, A
AF Mazurov, Dmitriy
Ilinskaya, Anna
Heidecker, Gisela
Filatov, Alexander
TI Role of O-Glycosylation and Expression of CD43 and CD45 on the Surfaces
of Effector T Cells in Human T Cell Leukemia Virus Type 1 Cell-to-Cell
Infection
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; VIROLOGICAL SYNAPSES; GAG PROTEIN;
B-CELLS; HTLV-I; TRANSMISSION; ANTIGEN; LYMPHOCYTES; MEMBRANE; ADHESION
AB We used replication-dependent retroviral vectors to identify cell surface antigens involved in the cell-to-cell transmission of human T cell leukemia virus type 1 (HTLV-1). We generated monoclonal antibodies (MAbs) against Jurkat T cells and selected several IgM MAbs that strongly inhibited HTLV-1 but not human immune deficiency virus type 1 (HIV-1) cell-to-cell infection. These MAbs recognized the so-called Tn antigen (GalNAc alpha 1-O-Ser/Thr) that arises on Jurkat cells from a mutation in the T-synthase-specific chaperone Cosmc and the consequent loss of O-glycan elongation. Anti-Tn MAbs precipitated two major O-glycan carrier proteins, CD43 and CD45, and caused a strong aggregation of Jurkat cells. The restoration of O-glycosylation in Jurkat cells by stably transducing the wild-type Cosmc gene resulted in a 3- to 4-fold increase in the level of surface expression of CD43 and enhanced HTLV-1 transmission 10-fold in comparison to that of parental cells. The short hairpin RNA (shRNA) knockdown of CD43 or CD45 expression in Jurkat-Cosmc, HBP-ALL, and CEM T cells decreased HTLV-1 infection severalfold. The knockdown of CD45 in Jurkat cells severely reduced both HTLV-1 and HIV-1 infections, but Cosmc coexpression partially rescued infection. HTLV-1 proteins, which assembled in small patches on Jurkat cells, formed large clusters on the surface of Jurkat-Cosmc cells. These data indicate that large aggregates of HTLV-1 assemblies are more infectious than multiple clustered virions. We suggest that heavily O-glycosylated CD43 and CD45 molecules render cells less adhesive, prevent inappropriate cell-cell contacts, and favor the assembly of HTLV-1 particles into large, highly infectious structures on the surface of T cells.
C1 [Mazurov, Dmitriy; Filatov, Alexander] Inst Immunol, Lab Immunochem, Moscow, Russia.
[Ilinskaya, Anna; Heidecker, Gisela] NCI, HIV Drug Resistance Program, Frederick, MD 21701 USA.
RP Mazurov, D (reprint author), Inst Immunol, Lab Immunochem, Moscow, Russia.
EM dvmazurov@yandex.ru
RI Ghartouchent, malek/B-9088-2012
FU Russian Foundation for Basic Research [RFBR 09-04-00426-a]; National
Institutes of Health; National Cancer Institute Center for Cancer
Research
FX This work has been supported by the Russian Foundation for Basic
Research, (grant RFBR 09-04-00426-a [D.M. and A.F.]) and the Intramural
Research Program of the National Institutes of Health and the National
Cancer Institute Center for Cancer Research (A.I. and G.H.).
NR 53
TC 12
Z9 12
U1 0
U2 2
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD MAR
PY 2012
VL 86
IS 5
BP 2447
EP 2458
DI 10.1128/JVI.06993-11
PG 12
WC Virology
SC Virology
GA 896AC
UT WOS:000300536800006
PM 22171268
ER
PT J
AU Samal, S
Khattar, SK
Kumar, S
Collins, PL
Samal, SK
AF Samal, Sweety
Khattar, Sunil K.
Kumar, Sachin
Collins, Peter L.
Samal, Siba K.
TI Coordinate Deletion of N-Glycans from the Heptad Repeats of the Fusion F
Protein of Newcastle Disease Virus Yields a Hyperfusogenic Virus with
Increased Replication, Virulence, and Immunogenicity
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; RESPIRATORY SYNCYTIAL VIRUS; PARAMYXOVIRUS
FUSION; MEMBRANE-FUSION; LINKED GLYCOSYLATION; NUCLEOTIDE-SEQUENCE;
ENVELOPE GLYCOPROTEINS; INFLUENZA-VIRUSES; STRUCTURAL BASIS; GENOME
SEQUENCE
AB The role of N-linked glycosylation of the Newcastle disease virus (NDV) fusion (F) protein in viral replication and pathogenesis was examined by eliminating potential acceptor sites using a reverse genetics system for the moderately pathogenic strain Beaudette C (BC). The NDV-BC F protein contains six potential acceptor sites for N-linked glycosylation at residues 85, 191, 366, 447, 471, and 541 (sites Ng1 to Ng6, respectively). The sites at Ng2 and Ng5 are present in heptad repeat (HR) domains HR1 and HR2, respectively, and thus might affect fusion. Each N-glycosylation site was eliminated individually by replacing asparagine (N) with glutamine (Q), and a double mutant (Ng2 + 5) involving the two HR domains was also made. Each mutant was successfully recovered by reverse genetics except for the one involving Ng6, which is present in the cytoplasmic domain. All of the F proteins expressed by the recovered mutant viruses were efficiently cleaved and transported to the infected-cell surface. None of the individual mutations affected viral fusogenicity, but the double mutation at Ng2 and Ng5 in HR1 and HR2 increased fusogenicity >12-fold. The single mutations at sites Ng1, Ng2, and Ng5 resulted in modestly reduced multicycle growth in vitro. These three single mutations were also the most attenuating in eggs and 1-day-old chicks and were associated with decreased replication and spread in 2-week-old chickens. In contrast, the combination of the mutations at Ng2 and Ng5 yielded a virus that, compared to the BC parent, replicated >100-fold more efficiently in vitro, was more virulent in eggs and chicks, replicated more efficiently in chickens with enhanced tropism for the brain and gut, and elicited stronger humoral cell responses. These results illustrate the effects of N-glycosylation of the F protein on NDV pathobiology and suggest that the N-glycans in HR1 and HR2 coordinately downregulate viral fusion and virulence.
C1 [Samal, Sweety; Khattar, Sunil K.; Kumar, Sachin; Samal, Siba K.] Univ Maryland, Virginia Maryland Reg Coll Vet Med, College Pk, MD 20742 USA.
[Collins, Peter L.] NIAID, Infect Dis Lab, Bethesda, MD 20892 USA.
RP Samal, SK (reprint author), Univ Maryland, Virginia Maryland Reg Coll Vet Med, College Pk, MD 20742 USA.
EM ssamal@umd.edu
FU NIAID [N01A060009]; NIAID, NIH
FX This research was supported by NIAID contract no. N01A060009 (85%
support) and NIAID, NIH Intramural Research Program (15% support).
NR 52
TC 12
Z9 14
U1 0
U2 2
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD MAR
PY 2012
VL 86
IS 5
BP 2501
EP 2511
DI 10.1128/JVI.06380-11
PG 11
WC Virology
SC Virology
GA 896AC
UT WOS:000300536800010
PM 22205748
ER
PT J
AU Suguitan, AL
Matsuoka, Y
Lau, YF
Santos, CP
Vogel, L
Cheng, LI
Orandle, M
Subbarao, K
AF Suguitan, Amorsolo L., Jr.
Matsuoka, Yumiko
Lau, Yuk-Fai
Santos, Celia P.
Vogel, Leatrice
Cheng, Lily I.
Orandle, Marlene
Subbarao, Kanta
TI The Multibasic Cleavage Site of the Hemagglutinin of Highly Pathogenic
A/Vietnam/1203/2004 (H5N1) Avian Influenza Virus Acts as a Virulence
Factor in a Host-Specific Manner in Mammals
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID LOWER RESPIRATORY-TRACT; A H5N1; PROCESSING ENDOPROTEASES; CONNECTING
PEPTIDE; FERRETS; HUMANS; CLEAVABILITY; INFECTION; MICE; DETERMINANT
AB Highly pathogenic avian influenza (HPAI) viruses of the H5 and H7 subtypes typically possess multiple basic amino acids around the cleavage site (MBS) of their hemagglutinin (HA) protein, a recognized virulence motif in poultry. To determine the importance of the H5 HA MBS as a virulence factor in mammals, recombinant wild-type HPAI A/Vietnam/1203/2004 (H5N1) viruses that possessed (H5N1) or lacked (Delta H5N1) the H5 HA MBS were generated and evaluated for their virulence in BALB/c mice, ferrets, and African green monkeys (AGMs) (Chlorocebus aethiops). The presence of the H5 HA MBS was associated with lethality, significantly higher virus titers in the respiratory tract, virus dissemination to extrapulmonary organs, lymphopenia, significantly elevated levels of proinflammatory cytokines and chemokines, and inflammation in the lungs of mice and ferrets. In AGMs, neither H5N1 nor Delta H5N1 virus was lethal and neither caused clinical symptoms. The H5 HA MBS was associated with mild enhancement of replication and delayed virus clearance. Thus, the contribution of H5 HA MBS to the virulence of the HPAI H5N1 virus varies among mammalian hosts and is most significant in mice and ferrets and less remarkable in nonhuman primates.
C1 [Suguitan, Amorsolo L., Jr.; Matsuoka, Yumiko; Lau, Yuk-Fai; Santos, Celia P.; Vogel, Leatrice; Subbarao, Kanta] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA.
[Cheng, Lily I.; Orandle, Marlene] NIAID, Comparat Med Branch, NIH, Bethesda, MD 20892 USA.
RP Subbarao, K (reprint author), NIAID, Infect Dis Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA.
EM ksubbarao@niaid.nih.gov
FU MedImmune
FX We thank Chris O'Donnell, Kobporn Boonnak, Elaine Lamirande of LID,
Jadon Jackson, and the staff of the Comparative Medicine Branch, NIAID,
for superior technical support for the animal studies conducted at the
NIH and Brad Finneyfrock for excellent assistance in performing the
studies in ferrets and AGMs at Bioqual. We are grateful to Hong Jin and
George Kemble of MedImmune and Li-Mei Chen and Ruben Donis from the CDC
for the reverse genetics plasmids and to Le Quynh Mai, National
Institute of Hygiene and Epidemiology (NI HE), Vietnam, for providing
the A/Vietnam/1203/2004 (H5N1) virus used in this study, which was made
available to us by Nancy Cox and Alexander Klimov, Influenza Division,
Centers for Disease Control and Prevention (CDC), Atlanta, GA. We also
thank David Tabor, Kathy Wang, and Xiamou Chen of MedImmune for their
assistance and support in conducting the qPCR assays for ferret cytokine
and chemokine genes.
NR 55
TC 36
Z9 37
U1 0
U2 7
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD MAR
PY 2012
VL 86
IS 5
BP 2706
EP 2714
DI 10.1128/JVI.05546-11
PG 9
WC Virology
SC Virology
GA 896AC
UT WOS:000300536800028
PM 22205751
ER
PT J
AU Ochsenbauer, C
Edmonds, TG
Ding, HT
Keele, BF
Decker, J
Salazar, MG
Salazar-Gonzalez, JF
Shattock, R
Haynes, BF
Shaw, GM
Hahn, BH
Kappes, JC
AF Ochsenbauer, Christina
Edmonds, Tara G.
Ding, Haitao
Keele, Brandon F.
Decker, Julie
Salazar, Maria G.
Salazar-Gonzalez, Jesus F.
Shattock, Robin
Haynes, Barton F.
Shaw, George M.
Hahn, Beatrice H.
Kappes, John C.
TI Generation of Transmitted/Founder HIV-1 Infectious Molecular Clones and
Characterization of Their Replication Capacity in CD4 T Lymphocytes and
Monocyte-Derived Macrophages
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID HUMAN-IMMUNODEFICIENCY-VIRUS; TYPE-1 R5 ENVELOPES;
CENTRAL-NERVOUS-SYSTEM; ANTIBODY NEUTRALIZATION; BIOLOGICAL PHENOTYPE;
SEXUAL TRANSMISSION; VIRAL DETERMINANTS; LYMPHOID-TISSUES; FUSION
INHIBITOR; TROPISM
AB Genome sequences of transmitted/founder (T/F) HIV-1 have been inferred by analyzing single genome amplicons of acute infection plasma viral RNA in the context of a mathematical model of random virus evolution; however, few of these T/F sequences have been molecularly cloned and biologically characterized. Here, we describe the derivation and biological analysis of ten infectious molecular clones, each representing a T/F genome responsible for productive HIV-1 clade B clinical infection. Each of the T/F viruses primarily utilized the CCR5 coreceptor for entry and replicated efficiently in primary human CD4(+) T lymphocytes. This result supports the conclusion that single genome amplification-derived sequences from acute infection allow for the inference of T/F viral genomes that are consistently replication competent. Studies with monocyte-derived macrophages (MDM) demonstrated various levels of replication among the T/F viruses. Although all T/F viruses replicated in MDM, the overall replication efficiency was significantly lower compared to prototypic "highly macrophage-tropic" virus strains. This phenotype was transferable by expressing the env genes in an isogenic proviral DNA backbone, indicating that T/F virus macrophage tropism mapped to Env. Furthermore, significantly higher concentrations of soluble CD4 were required to inhibit T/F virus infection compared to prototypic macrophage-tropic virus strains. Our findings suggest that the acquisition of clinical HIV-1 subtype B infection occurs by mucosal exposure to virus that is not highly macrophage tropic and that the generation and initial biological characterization of 10 clade B T/F infectious molecular clones provides new opportunities to probe virus-host interactions involved in HIV-1 transmission.
C1 [Ochsenbauer, Christina; Ding, Haitao; Decker, Julie; Salazar, Maria G.; Salazar-Gonzalez, Jesus F.; Kappes, John C.] Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA.
[Edmonds, Tara G.; Kappes, John C.] Univ Alabama Birmingham, Dept Pathol, Birmingham, AL USA.
[Kappes, John C.] Univ Alabama Birmingham, Dept Microbiol, Birmingham, AL USA.
[Keele, Brandon F.] NCI Frederick, SAIC Frederick Inc, Frederick, MD USA.
[Shattock, Robin] Univ London Imperial Coll Sci Technol & Med, London, England.
[Haynes, Barton F.] Duke Univ, Sch Med, Dept Med, Duke Human Vaccine Inst, Durham, NC 27706 USA.
[Haynes, Barton F.] Duke Univ, Sch Med, Dept Immunol, Duke Human Vaccine Inst, Durham, NC USA.
[Shaw, George M.; Hahn, Beatrice H.] Univ Penn, Dept Med, Philadelphia, PA 19104 USA.
[Shaw, George M.; Hahn, Beatrice H.] Univ Penn, Dept Microbiol, Philadelphia, PA 19104 USA.
[Kappes, John C.] Birmingham Vet Affairs Med Ctr, Res Serv, Birmingham, AL USA.
RP Kappes, JC (reprint author), Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA.
EM kappesjc@uab.edu
RI Ghartouchent, malek/B-9088-2012
FU NIH Center for HIV/AIDS Vaccine Immunology (CHAVI) [UO1-AI067854]; Bill
and Melinda Gates Foundation's Collaboration for AIDS Vaccine
Discovery/Comprehensive Antibody Vaccine Immune Monitoring Consortium
[38619]; Bill and Melinda Gates Foundation [37874]; facilities of the
Virology, Biostatistics, and Genetic Sequencing cores of the UAB Center
for AIDS Research [P30-AI-27767]; Genetically Defined Microbe and
Expression Core of the UAB Mucosal HIV and Immunobiology Center [R24
DK-64400]; Department of Veterans Affairs Medical Center, Research
Services; NIH [AI007439]
FX This study was supported by the NIH Center for HIV/AIDS Vaccine
Immunology (CHAVI; UO1-AI067854); the Bill and Melinda Gates
Foundation's Collaboration for AIDS Vaccine Discovery/Comprehensive
Antibody Vaccine Immune Monitoring Consortium (grant 38619); a Bill and
Melinda Gates Foundation Grand Challenges grant (grant 37874); the
facilities of the Virology, Biostatistics, and Genetic Sequencing cores
of the UAB Center for AIDS Research (P30-AI-27767); and the Genetically
Defined Microbe and Expression Core of the UAB Mucosal HIV and
Immunobiology Center (R24 DK-64400). Research was also supported by a
Merit Review Award (J.C.K.) and a Research Career Scientist Award
(J.C.K.) from the Department of Veterans Affairs Medical Center,
Research Services. T.G.E. is supported by NIH training grant AI007439.
NR 71
TC 123
Z9 123
U1 3
U2 14
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD MAR
PY 2012
VL 86
IS 5
BP 2715
EP 2728
DI 10.1128/JVI.06157-11
PG 14
WC Virology
SC Virology
GA 896AC
UT WOS:000300536800029
PM 22190722
ER
PT J
AU Dobrikova, EY
Goetz, C
Walters, RW
Lawson, SK
Peggins, JO
Muszynski, K
Ruppel, S
Poole, K
Giardina, SL
Vela, EM
Estep, JE
Gromeier, M
AF Dobrikova, Elena Y.
Goetz, Christian
Walters, Robert W.
Lawson, Sarah K.
Peggins, James O.
Muszynski, Karen
Ruppel, Sheryl
Poole, Karyol
Giardina, Steven L.
Vela, Eric M.
Estep, James E.
Gromeier, Matthias
TI Attenuation of Neurovirulence, Biodistribution, and Shedding of a
Poliovirus:Rhinovirus Chimera after Intrathalamic Inoculation in Macaca
fascicularis
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID RIBOSOME ENTRY SITE; INTERGENERIC POLIOVIRUS RECOMBINANTS; TRANSLATION
INITIATION; ONCOLYTIC POLIOVIRUS; GENETIC ADAPTATION; NONCODING REGION;
MESSENGER-RNA; BINDING; GLIOMA; PHOSPHORYLATION
AB A dependence of poliovirus on an unorthodox translation initiation mode can be targeted selectively to drive viral protein synthesis and cytotoxicity in malignant cells. Transformed cells are naturally susceptible to poliovirus, due to widespread ectopic upregulation of the poliovirus receptor, Necl-5, in ectodermal/neuroectodermal cancers. Viral tumor cell killing and the host immunologic response it engenders produce potent, lasting antineoplastic effects in animal tumor models. Clinical application of this principle depends on unequivocal demonstration of safety in primate models for paralytic poliomyelitis. We conducted extensive dose-range-finding, toxicity, biodistribution, shedding, and neutralizing antibody studies of the prototype oncolytic poliovirus recombinant, PVS-RIPO, after intrathalamic inoculation in Macaca fascicularis. These studies suggest that intracerebral PVS-RIPO inoculation does not lead to viral propagation in the central nervous system (CNS), does not cause histopathological CNS lesions or neurological symptoms that can be attributed to the virus, is not associated with extraneural virus dissemination or replication and does not induce shedding of virus with stool. Intrathalamic PVS-RIPO inoculation induced neutralizing antibody responses against poliovirus serotype 1 in all animals studied.
C1 [Dobrikova, Elena Y.; Goetz, Christian; Walters, Robert W.; Lawson, Sarah K.; Gromeier, Matthias] Duke Univ, Med Ctr, Dept Surg, Div Neurosurg, Durham, NC 27710 USA.
[Peggins, James O.] NCI, Toxicol & Pharmacol Branch, Frederick, MD 21701 USA.
[Muszynski, Karen] NCI, Biol Res Branch, Frederick, MD 21701 USA.
[Ruppel, Sheryl; Poole, Karyol; Giardina, Steven L.] NCI Frederick, Biopharmaceut Dev Program, SAIC Frederick Inc, Frederick, MD USA.
[Vela, Eric M.; Estep, James E.] Battelle Mem Inst, Columbus, OH USA.
RP Gromeier, M (reprint author), Duke Univ, Med Ctr, Dept Surg, Div Neurosurg, Durham, NC 27710 USA.
EM grome001@mc.duke.edu
FU National Cancer Institute, National Institutes of Health [NO1-CO-12400];
Division of Cancer Treatment and Diagnosis, National Cancer Institute,
National Institutes of Health; PHS [CA124756, CA140510]
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 NO1-CO-12400 and also supported in part through the NCI-RAID
Program of the Developmental Therapeutics Program, Division of Cancer
Treatment and Diagnosis, National Cancer Institute, National Institutes
of Health.; This study was partly supported by PHS grants CA124756 and
CA140510 (M.G.). The content of this publication does not necessarily
reflect the views or policies of the Department of Health and Human
Services, nor does mention of trade names, commercial products, or
organizations imply endorsement by the U.S. Government.
NR 48
TC 10
Z9 10
U1 0
U2 3
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD MAR
PY 2012
VL 86
IS 5
BP 2750
EP 2759
DI 10.1128/JVI.06427-11
PG 10
WC Virology
SC Virology
GA 896AC
UT WOS:000300536800032
PM 22171271
ER
PT J
AU Elleder, D
Kim, O
Padhi, A
Bankert, JG
Simeonov, I
Schuster, SC
Wittekindt, NE
Motameny, S
Poss, M
AF Elleder, Daniel
Kim, Oekyung
Padhi, Abinash
Bankert, Jason G.
Simeonov, Ivan
Schuster, Stephan C.
Wittekindt, Nicola E.
Motameny, Susanne
Poss, Mary
TI Polymorphic Integrations of an Endogenous Gammaretrovirus in the Mule
Deer Genome
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID FELINE LEUKEMIA VIRUSES; INSERTIONAL POLYMORPHISMS; RETROVIRAL ELEMENTS;
IDENTIFICATION; PHYLOGENIES; SEQUENCES; SHEEP; MITOCHONDRIAL; ORIGIN;
GENES
AB Endogenous retroviruses constitute a significant genomic fraction in all mammalian species. Typically they are evolutionarily old and fixed in the host species population. Here we report on a novel endogenous gammaretrovirus (CrERV gamma; for cervid endogenous gammaretrovirus) in the mule deer (Odocoileus hemionus) that is insertionally polymorphic among individuals from the same geographical location, suggesting that it has a more recent evolutionary origin. Using PCR-based methods, we identified seven CrERV gamma proviruses and demonstrated that they show various levels of insertional polymorphism in mule deer individuals. One CrERV gamma provirus was detected in all mule deer sampled but was absent from white-tailed deer, indicating that this virus originally integrated after the split of the two species, which occurred approximately one million years ago. There are, on average, 100 CrERV gamma copies in the mule deer genome based on quantitative PCR analysis. A CrERV gamma provirus was sequenced and contained intact open reading frames (ORFs) for three virus genes. Transcripts were identified covering the entire provirus. CrERV gamma forms a distinct branch of the gammaretrovirus phylogeny, with the closest relatives of CrERV gamma being endogenous gammaretroviruses from sheep and pig. We demonstrated that white-tailed deer (Odocoileus virginianus) and elk (Cervus canadensis) DNA contain proviruses that are closely related to mule deer CrERV gamma in a conserved region of pol; more distantly related sequences can be identified in the genome of another member of the Cervidae, the muntjac (Muntiacus muntjak). The discovery of a novel transcriptionally active and insertionally polymorphic retrovirus in mammals could provide a useful model system to study the dynamic interaction between the host genome and an invading retrovirus.
C1 [Elleder, Daniel; Kim, Oekyung; Padhi, Abinash; Bankert, Jason G.; Poss, Mary] Penn State Univ, Dept Biol, University Pk, PA 16802 USA.
[Simeonov, Ivan] Penn State Univ, Dept Stat, University Pk, PA 16802 USA.
[Schuster, Stephan C.; Wittekindt, Nicola E.] Penn State Univ, Dept Biochem Microbiol & Mol Biol, University Pk, PA 16802 USA.
[Motameny, Susanne] Univ Cologne, Cologne Ctr Genom, D-50931 Cologne, Germany.
[Poss, Mary] NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA.
RP Poss, M (reprint author), Penn State Univ, Dept Biol, University Pk, PA 16802 USA.
EM mposs@bx.psu.edu
RI Wittekindt, Nicola/G-3469-2013; Elleder, Daniel/G-3551-2014
OI Wittekindt, Nicola/0000-0002-3310-0919;
FU USGS [06HQAG0131]
FX This work was supported by USGS grant 06HQAG0131.
NR 53
TC 10
Z9 10
U1 0
U2 11
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD MAR
PY 2012
VL 86
IS 5
BP 2787
EP 2796
DI 10.1128/JVI.06859-11
PG 10
WC Virology
SC Virology
GA 896AC
UT WOS:000300536800036
PM 22190723
ER
PT J
AU Fontana, J
Cardone, G
Heymann, JB
Winkler, DC
Steven, AC
AF Fontana, Juan
Cardone, Giovanni
Heymann, J. Bernard
Winkler, Dennis C.
Steven, Alasdair C.
TI Structural Changes in Influenza Virus at Low pH Characterized by
Cryo-Electron Tomography
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID VIRAL MEMBRANE-FUSION; MATRIX PROTEIN M1; A VIRUS; 3-DIMENSIONAL
STRUCTURE; CONFORMATIONAL CHANGE; ELECTRON-MICROSCOPY; DISULFIDE BONDS;
HEMAGGLUTININ; ANTIBODY; M2
AB Influenza virus enters host cells by endocytosis. The low pH of endosomes triggers conformational changes in hemagglutinin (HA) that mediate fusion of the viral and endosomal membranes. We have used cryo-electron tomography to visualize influenza A virus at pH 4.9, a condition known to induce fusogenicity. After 30 min, when all virions are in the postfusion state, dramatic changes in morphology are apparent: elongated particles are no longer observed, larger particles representing fused virions appear, the HA spikes become conspicuously disorganized, a layer of M1 matrix protein is no longer resolved on most virions, and the ribonucleoprotein complexes (RNPs) coagulate on the interior surface of the virion. To probe for intermediate states, preparations were imaged after 5 min at pH 4.9. These virions could be classified according to their glycoprotein arrays (organized or disorganized) and whether or not they have a resolved M1 layer. Employing subtomogram averaging, we found, in addition to the neutral-pH state of HA, two intermediate conformations that appear to reflect an outwards movement of the fusion peptide and rearrangement of the HA1 subunits, respectively. These changes are reversible. The tomograms also document pH-induced changes affecting the M1 layer that appear to render the envelope more pliable and hence conducive to fusion. However, it appears desirable for productive infection that fusion should proceed before the RNPs become coagulated with matrix protein, as eventually happens at low pH.
C1 [Fontana, Juan; Cardone, Giovanni; Heymann, J. Bernard; Winkler, Dennis C.; Steven, Alasdair C.] NIAMSD, Struct Biol Lab, NIH, Bethesda, MD 20892 USA.
RP Steven, AC (reprint author), NIAMSD, Struct Biol Lab, NIH, Bethesda, MD 20892 USA.
EM stevena@mail.nih.gov
RI Fontana, Juan/A-9138-2009;
OI Fontana, Juan/0000-0002-9084-2927; Heymann, Bernard/0000-0002-8872-5326
FU National Institute of Arthritis and Musculoskeletal and Skin Diseases of
the National Institutes of Health
FX This research was supported by the Intramural Research Program of the
National Institute of Arthritis and Musculoskeletal and Skin Diseases of
the National Institutes of Health.
NR 47
TC 53
Z9 55
U1 1
U2 13
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD MAR
PY 2012
VL 86
IS 6
BP 2919
EP 2929
DI 10.1128/JVI.06698-11
PG 11
WC Virology
SC Virology
GA 897GC
UT WOS:000300634100003
PM 22258245
ER
PT J
AU Liu, XQ
Li, QX
Dowdell, K
Fischer, ER
Cohen, JI
AF Liu, XueQiao
Li, Qingxue
Dowdell, Kennichi
Fischer, Elizabeth R.
Cohen, Jeffrey I.
TI Varicella-Zoster Virus ORF12 Protein Triggers Phosphorylation of ERK1/2
and Inhibits Apoptosis
SO JOURNAL OF VIROLOGY
LA English
DT Article
ID SARCOMA-ASSOCIATED HERPESVIRUS; LATENCY-ASSOCIATED PROTEIN; KINASE
PATHWAYS; SIGNALING PATHWAY; MAPK PATHWAY; ACTIVATION; REPLICATION;
INFECTION; NEURONS; VZV
AB Mitogen-activated protein kinases (MAPKs) are a family of serine-threonine protein kinases involved in many cellular processes, including cell proliferation, differentiation, inflammation, and cell death. Activation of several MAPKs, including extracellular signal-regulated kinase 1 and 2 (ERK1/2), p38, and c-Jun N-terminal kinase (JNK), results in stimulation of activator protein 1 (AP-1), which promotes gene transcription. Previous studies have demonstrated that varicella-zoster virus (VZV) infection activates ERK1/2, p38, and JNK to promote viral replication, but the underlying mechanism(s) is unclear. To identify viral proteins responsible for the activation of MAPK, we used a proteomic approach to screen viral proteins for AP-1 promoter activation by an AP-1-luciferase reporter assay. We found that VZV ORF12 protein, located in the tegument of virions, enhances AP-1 reporter activity. This effect of ORF12 protein was markedly inhibited by a MAPK/ERK kinase 1 and 2 (MEK1/2) inhibitor (U0126), partially blocked by a p38 inhibitor (SB202190), but not inhibited by a JNK inhibitor (SP600125). Expression of VZV ORF12 protein in cells resulted in phosphorylation of ERK1/2 and p38 but not JNK. Infection of cells with a VZV ORF12 deletion mutant resulted in reduced levels of phosphorylated ERK1/2 (p-ERK1/2) compared to infection with wild-type VZV. Furthermore, deletion of ORF12 rendered VZV-infected cells more susceptible to staurosporine-induced apoptosis. In conclusion, VZV ORF12 protein activates the AP-1 pathway by selectively triggering the phosphorylation of ERK1/2 and p38. Cells infected with a VZV ORF12 deletion mutant have reduced levels of p-ERK1/2 and are more susceptible to apoptosis than cells infected with wild-type VZV.
C1 [Liu, XueQiao; Li, Qingxue; Dowdell, Kennichi; Cohen, Jeffrey I.] NIH, Med Virol Sect, Infect Dis Lab, Bethesda, MD 20892 USA.
[Fischer, Elizabeth R.] NIH, Res Technol Sect, Res Technol Branch, Rocky Mt Labs, Hamilton, MT USA.
RP Cohen, JI (reprint author), NIH, Med Virol Sect, Infect Dis Lab, Bldg 10, Bethesda, MD 20892 USA.
EM jcohen@niaid.nih.gov
FU National Institute of Allergy and Infectious Diseases
FX This work was supported by the Intramural Research Program of the
National Institute of Allergy and Infectious Diseases.
NR 35
TC 26
Z9 29
U1 0
U2 9
PU AMER SOC MICROBIOLOGY
PI WASHINGTON
PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA
SN 0022-538X
J9 J VIROL
JI J. Virol.
PD MAR
PY 2012
VL 86
IS 6
BP 3143
EP 3151
DI 10.1128/JVI.06923-11
PG 9
WC Virology
SC Virology
GA 897GC
UT WOS:000300634100023
PM 22238304
ER
PT J
AU Del Prete, GQ
Kearney, MF
Spindler, J
Wiegand, A
Chertova, E
Roser, JD
Estes, JD
Hao, XP
Trubey, CM
Lara, A
Lee, K
Chaipan, C